PMID- 10180239
TI - How technology is affecting the way we work.
PMID- 10180240
TI - Anticipating change: an operational response.
PMID- 10180241
TI - Healthcare's professional image: an element of success.
PMID- 10180242
TI - Medicare HMO: an education for the elderly.
PMID- 10180243
TI - Integrating home health care into your IT strategy: electronic communications
maximize the benefits of providing care beyond your inpatient facilities.
PMID- 10180244
TI - Service quality: the next frontier in healthcare?
PMID- 10180245
TI - The politics of healthcare: 1998.
PMID- 10180246
TI - NAHAM and AAHAM to collaborate on key programs.
PMID- 10180247
TI - Healthcare access in the new millennium.
PMID- 10180248
TI - Improving identification and communication with referring and primary care
physicians.
PMID- 10180249
TI - Choosing the right ladder: creating a new model for healthcare.
AB - Healthcare in America needs to be fundamentally restructured if we hope to
successfully overcome issues relating to cost and health outcomes. This will
require a basic change in mindsets. We can no longer think of health as the mere
absence of disease, nor can we afford to pigeonhole responsibility for achieving
and maintaining health on a community basis. Health is not the responsibility of
the local hospital, or the Public Health agency, or the inner-city clinic, or the
police department, or the fire department, or the day-care center. It is the
community's responsibility. We must be careful as we engage ourselves in this
effort not to expect overnight success. Americans are notorious for wanting quick
fixes. We cannot hope to achieve that kind of result in this effort. Although we
may see some level of immediate result, this is not an endeavor where we will be
able to measure huge payoffs in months or quarters. The real benefits may be a
generation down the road. But if we preserve, our children will be able to look
back on our efforts with gratitude that we had the courage to stay the course and
do what needed to be done.
PMID- 10180250
TI - Health care prevention: real or rhetoric?
PMID- 10180251
TI - COBRA: legislation and its import.
AB - COBRA refers to the provision in the 1985 Consolidated Omnibus Reconciliation Act
that allows terminated employees to continue to buy health insurance at group
rates, and that allow families who lose their coverage through the death or
divorce of the employee also to continue to buy coverage. Analysis of COBRA shows
that it is too expensive and too exclusionary for many workers, particularly low
income ones, to benefit.
PMID- 10180252
TI - Self-Insured health care plans: are they fair to employees with HIV/AIDS?
AB - A literature search reveals a number of instances where people with AIDS (PWAs)
have limits placed on their health care by self-insured firms. Some firms cite
the high cost of health care for AIDS as the motivation for their decision.
Research demonstrates, however, that AIDS is not the only high-priced disease to
treat. Treatment for lung cancer is costly as well. In many cases, unprotected
sex leads to HIV/AIDS and lung cancer is strongly linked to tobacco use.
Therefore, lung cancer can be studied as a comparison disease for issues relating
to health care coverage of PWAs. A literature search also shows that no examples
of limitations on health care were found among lung cancer patients. A 1992
Supreme Court decision did not restrict the inequitable access to health care
through self-insured plans for AIDS patients. When employees of self-insured
firms exhaust their insurance benefits, which can occur quickly, they apply for
Medicaid or Medicare benefits. As a result, the government's burden is increased
in the care of PWAs. The issue, therefore, should be to ensure that employees of
self-insured firms have equal access to health care since there are other serious
diseases, such as lung cancer, that are also expensive to treat.
PMID- 10180253
TI - Positioning for capitation in long-term care: a profile of vertical integration
strategies in health and social service organizations.
AB - During the next decade, the population over age 65 is expected to increase by 11%
while the population over age 85 is expected to increase by 42%. These
projections suggest that many organizations which currently provide services to
the aged will be required to design a range of new products and services for this
diverse population. Vertically integrated services provide a viable opportunity
to competitively position an organization to respond to the diverse needs of an
aged market. Since vertical integration will be essential in negotiating capitate
contracts for the aged in the future, this study examined the extent of vertical
integration in 116 health and social service organizations in an urban market
with an expanding geriatric population.
PMID- 10180254
TI - Insurance status among HIV+ Nebraskans.
AB - OBJECTIVES: (1) To measure the rates of insurance in a population of HIV+ status.
(2) To test an hypothesis that persons with AIDS are more likely to be uninsured
than those who are HIV+ without AIDS. (3) To test the hypothesis that persons who
are HIV+ experience difficulties maintaining their health insurance. METHODS:
Clients of three service agencies were surveyed. Demographic information was used
to eliminate duplicate responses. Of the potential 480 respondents, 238 returned
the surveys, reflecting approximately 10% of the estimated number of HIV+ persons
in Nebraska. Descriptive techniques were used to analyze the data, and chi-square
techniques were used in group comparisons. RESULTS: Forty-three percent of the
respondents were covered by private insurance, and 22% lacked any health
insurance coverage. Persons with AIDS were less likely to have private insurance
coverage and more likely to be receiving Medicaid coverage, but less likely to be
uninsured. HIV+ test results contributed to a loss of insurance for 25
respondents, and HIV or AIDS positive was a reason for 29 respondents being
denied insurance.
PMID- 10180255
TI - Marijuana use among Miami's adolescents, 1992.
AB - This analysis examines the use of marijuana by 458 adolescents in Dade County,
Florida public schools in 1992. Statistically significant factors which tended to
increase the probability of marijuana use by adolescents include: the fact that
their peers were using marijuana, the fact that they were white, male, and their
ready access to the substance. Although not statistically significant,
adolescents were less likely to use marijuana if they knew of the risks
associated with marijuana use. The only statistically significant variables which
inhibited marijuana use by Miami adolescents was the fact that religion was an
important part of their lives, that their fathers resided with them, and that
they were "good" students (receiving mostly "A's" and "B's"). Not significantly
related to marijuana use were a number of other variables, including family
related variables (whether adolescents lived with their mothers or alone); and
whether someone in the family had a problem with drugs or alcohol. Similarly,
early cigarette smoking and alcohol consumption did not serve as gateways to
later marijuana use. Extracurricular school activities (athletics, music, school
clubs, and other activities) were all unrelated to the use of marijuana by
adolescents. Marijuana users tended to be in higher grades (9 through 12), though
this was not significant.
PMID- 10180256
TI - Smoking policy in long-term care: a survey of administrators in San Francisco.
AB - Despite the fact that smoking is a ubiquitous yet potentially hazardous behavior
in long-term care settings, little previous investigation has been made into the
construction or implementation of policy to manage smoking by elderly residents.
This survey of administrators in long-term care facilities in San Francisco city
and county reveals that fire and safety issues were the prime forces motivating
smoking policy, which operated through control of behavior rather than by other
available means, such as the use of fire retardant aprons. Although all
facilities permitted smoking, a hierarchy of limit setting strategies was
adopted, strategies which successively and evermore intrusively overrode the
resident's autonomy and turned smoking policy from beneficent philosophy into a
coercive moral statement. Arranged in order of frequency of occurrence and
increasing degree of restriction, these strategies were: (a) designating
appropriate locations; (b) controlling smoking opportunities and materials; (c)
requiring staff supervision or help; (d) limiting the availability of staff help;
and (e) writing Doctor's orders. By acknowledging the tensions between ambivalent
goals inherent in smoking in long-term care, administrators could devise policies
and procedures that are both supportive of collective rights and less corrosive
of individual ones.
PMID- 10180257
TI - Ambulatory surgery: 10 frequently asked questions.
PMID- 10180258
TI - The American College of Surgeons Oncology Group: its genesis and future
directions.
PMID- 10180259
TI - HCFA issues. Stark II proposed rules.
PMID- 10180260
TI - Taking charge: specialty surgeons take on managed care.
PMID- 10180261
TI - Statement on ultrasound examinations by surgeons. Committee on Emerging Surgical
Technology and Education, American College of Surgeons.
PMID- 10180262
TI - In their own words. The Five-Year Review, E&M services, and ACS leadership.
PMID- 10180263
TI - Medical education.
PMID- 10180264
TI - How do hospitalists fit with integrated healthcare?
PMID- 10180265
TI - Do integrated systems need to own HMOs?
PMID- 10180266
TI - Meeting the challenges of managed care.
PMID- 10180267
TI - HMO growth trends.
PMID- 10180268
TI - Building a new post-merger governance culture.
PMID- 10180270
TI - HMOs losses: new provider warning signals for 1998.
PMID- 10180269
TI - United HealthCare buys Humana.
PMID- 10180272
TI - The CEO of an IDS: life at ground zero.
PMID- 10180271
TI - What consumer backlash?
PMID- 10180273
TI - Our new theme song.
PMID- 10180274
TI - Memorandum of understanding between the Food and Drug Administration and the
National Institutes of Health's National Institute of Dental Research--FDA.
Notice.
AB - The Food and Drug Administration (FDA) is providing notice of a memorandum of
understanding (MOU) between the National Institutes of Health's National
Institute of Dental Research (NIDR) and three of FDA's line organizations: the
Center for Devices and Radiological Health, the Center for Drug Evaluation and
Research, and the Center for Biologics Evaluation and Research. The purpose of
the MOU is to facilitate interactions between NIDR and FDA regarding improvements
in the quality and relevance of preclinical and clinical research, which is
directed to the development of products for use in oral healthcare.
PMID- 10180275
TI - Draft guidance for industry; exports and imports under the FDA Export Reform and
Enhancement Act of 1996--FDA. Notice.
AB - The Food and Drug Administration (FDA) is announcing the availability of a draft
guidance document entitled, "FDA Draft Guidance for Industry on: Exports and
Imports Under the FDA Export Reform and Enhancement Act of 1996." The draft
guidance document addresses issues pertaining to the exportation of human drugs,
animal drugs, biologics, food additives, and devices as well as the importation
of components, parts, accessories, or other articles for incorporation or further
processing into articles intended for export.
PMID- 10180276
TI - Medicare program; update of ratesetting methodology, payment rates, payment
policies, and the list of covered surgical procedures for ambulatory surgical
centers effective October 1, 1998--HCFA. Proposed rule.
AB - In this rule we propose to--Update the criteria for determining which surgical
procedures can be appropriately and safely performed in an ambulatory surgical
center (ASC); Make additions to and deletions from the current list of Medicare
covered ASC procedures based on the revised criteria; Rebase the ASC payment
rates using cost, charge, and utilization data collected by a 1994 survey of
ASCs; Refine the ratesetting methodology that was implemented by a final notice
published on February 8, 1990 in the Federal Register; Require that ASC payment,
coverage, and wage index updates be implemented annually on January 1 rather than
having these updates occur randomly throughout the year; Reduce regulatory
burden; and Make several technical policy changes. This proposed rule implements
requirements of section 1833(i)(1) and (2) of the Social Security Act.
PMID- 10180277
TI - CLIA program; simplifying CLIA regulations relating to accreditation, exemption
of laboratories under a state licensure program, proficiency testing, and
inspection--HCFA. Correction.
PMID- 10180278
TI - Administrative practices and procedures; internal review of agency decisions--
FDA. Direct final rule.
AB - The Food and Drug Administration (FDA) is amending its regulations governing the
review of agency decisions by inserting a statement that sponsors, applicants, or
manufacturers of drugs (including biologics) or devices may request review of a
scientific controversy by an appropriate scientific advisory panel, or an
advisory committee. This action is being taken to clarify the availability of
review of scientific controversies by such advisory panels and committees.
Elsewhere in this issue of the Federal Register, FDA is publishing a companion
proposed rule. If any significant adverse comment is received, FDA will withdraw
the direct final rule and will follow its usual procedures for notice-and-comment
rulemaking based on the companion proposed rule.
PMID- 10180279
TI - Administrative practices and procedures; internal agency review of decisions;
companion document to direct final rule--FDA. Proposed rule.
AB - The Food and Drug Administration (FDA) is proposing to amend the regulations
governing the review of agency decisions by inserting a statement that sponsors,
applicants, or manufacturers of drugs (including biologics) or devices may
request review of a scientific controversy by an appropriate scientific advisory
panel, or an advisory committee. The agency is taking this action to clarify the
availability of review of scientific controversies by such advisory panels or
committees. This proposed rule is a companion document to a direct final rule
published elsewhere in this issue of the Federal Register. If FDA receives any
significant adverse comment, the direct final rule will be withdrawn, and the
comments will be considered in the development of a final rule using usual notice
and comment rulemaking based on this proposed rule.
PMID- 10180280
TI - Health insurance reform: national standard employer identifier--HCFA. Proposed
rule.
AB - This rule proposes a standard for a national employer identifier and requirements
concerning its use by health plans, health care clearinghouses, and health care
providers. The health plans, health care clearinghouses, and health care
providers would use the identifier, among other uses, in connection with certain
electronic transactions. The use of this identifier would improve the Medicare
and Medicaid programs, and other Federal health programs and private health
programs, and the effectiveness and efficiency of the health care industry in
general, by simplifying the administration of the system and enabling the
efficient electronic transmission of certain health information. It would
implement some of the requirements of the Administrative Simplification subtitle
of the Health Insurance Portability and Accountability Act of 1996.
PMID- 10180281
TI - Draft guideline for the prevention of surgical site infection, 1998--CDC. Notice.
AB - This notice is a request for review of and comment on the Draft Guideline for the
Prevention of Surgical Site Infection, 1998. The guideline consists of two parts:
Part 1. "Surgical Site Infection, an Overview" and Part 2. "Recommendations for
the Prevention of Surgical Site Infections", and was prepared by the Hospital
Infection Control Practices Advisory Committee (HICPAC), the Hospital Infection
Program (HIP), the National Center for Infectious Diseases (NCID), CDC.
PMID- 10180282
TI - Medicare and Medicaid programs; hospital conditions of participation;
identification of potential organ, tissue, and eye donors and transplant
hospitals' provision of transplant-related data--HCFA. Final rule.
AB - This final rule addresses only provisions relating to organ donation and
transplantation. It imposes several requirements a hospital must meet that are
designed to increase organ donation. One of these requirements is that a hospital
must have an agreement with the Organ Procurement Organization (OPO) designated
by the Secretary, under which the hospital will contact the OPO in a timely
manner about individuals who die or whose death is imminent in the hospital. The
OPO will then determine the individual's medical suitability for donation. As
well, the hospital must have an agreement with at least one tissue bank and at
least one eye bank to cooperative in the retrieval processing, preservation,
storage, and distribution of tissue and eyes, as long as the agreement does not
interfere with organ donation. The final rule requires a hospital to ensure, in
collaboration with the OPO with which it has an agreement, that the family of
every potential donor is informed of its opinion to donate organs or tissues or
not to donate. Under the final rule, hospital must work with the OPO and at least
one tissue bank and one eye bank in educating staff on donation issues, reviewing
death records to improve identification of potential donors, and maintaining
potential donors while necessary testing and placement of organs and tissues take
place. In addition, transplant hospitals must provide organ-transplant-related
data, as requested by the OPTN, the Scientific Registry, and the OPOs. The
hospital must also provide, if requested, such data directly to the Department.
PMID- 10180283
TI - Medicare program; payment for teleconsultations in rural health professional
shortage areas--HCFA. Proposed rule.
AB - This proposed rule would implement parts of section 4206 of the Balanced Budget
Act of 1997 by amending our regulations to provide for payment for professional
consultation by a physician and certain other practitioners via interactive
telecommunication systems. Payment may be made if the physician or other
practitioner is furnishing a service for which payment may be made under Medicare
to a beneficiary residing in a rural area that is designated as a health
professional shortage area. This proposed rule would also establish a methodology
for determining the amount of payments made for the consultation.
PMID- 10180284
TI - Food labeling: health claims; antioxidant vitamins C and E and the risk of
atherosclerosis, coronary heart disease, certain cancers, and cataracts--FDA.
Interim final rule.
AB - The Food and Drug Administration (FDA) is issuing an interim final rule to
prohibit the use on foods of a claim relating to the relationship between
antioxidant vitamins C and E and the risk in adults of atherosclerosis, coronary
heart disease, certain cancers, and cataracts. This rule is in response to a
notification of a health claim submitted under section 303 of the FDA
Modernization Act of 1997 (FDAMA). FDA has reviewed statements that the
petitioner submitted in that notification, and, in conformity with the
requirements of FDAMA, the agency is prohibiting the claim because the statements
submitted as the basis of the claim are not "authoritative statements" of a
scientific body, as required by FDAMA; therefore, section 303 of FDAMA does not
authorize use of this claim. As provided for in section 301 of FDAMA, this rule
is effective immediately upon publication.
PMID- 10180285
TI - Food labeling: health claims; antioxidant vitamin A and beta-carotene and the
risk in adults of atherosclerosis, coronary heart disease, and in cancers--FDA.
Interim final rule.
AB - The Food and Drug Administration (FDA) is issuing an interim final rule to
prohibit the use on foods of a claim relating to the relationship between
antioxidant vitamins A and beta-carotene and the risk in adults of
atherosclerosis, coronary heart disease, amd certain cancers. This interim final
rule is in response to a notification of a health claim submitted under section
303 of the FDA Modernization Act of 1997 (FDAMA). FDA has reviewed statements
that the petitioner submitted in that notification, and, in conformity with the
requirements of FDAMA, the agency is prohibiting the claim because the statements
submitted as the basis of the claim are not "authoritative statements" of a
scientific body, as required by FDAMA; therefore, section 303 of FDAMA does not
authorize use of this claim. As provided for in section 301 of FDAMA, this
interim final rule is effective immediately upon publication.
PMID- 10180286
TI - Food labeling: health claims; B-complex vitamins, lowered homocysteine levels,
and the risk in adults of cardiovascular disease--FDA. Interim final rule.
AB - The Food and Drug Administration (FDA) is issuing an interim final rule to
prohibit the use on foods of a claim relating to the relationship between B
complex vitamins (folic acid, vitamin B6, vitamin B12), lowering elevated serum
homocysteine levels, and the risk in adults of cardiovascular disease. This
interim final rule is in response to a notification of a health claim submitted
under section 303 of the FDA Modernization Act of 1997 (FDAMA). FDA has reviewed
statements that the petitioner submitted in that notification, and, in conformity
with the requirements of FDAMA, the agency is prohibiting the claim because the
statements submitted as the basis of the claim are not "authoritative statements"
of a scientific body, as required by FDAMA; therefore, section 303 of FDAMA does
not authorize use of this claim. As provided for in section 301 of FDAMA, this
rule is effective immediately upon publication.
PMID- 10180287
TI - Food labeling: health claims; calcium consumption by adolescents and adults, bone
density and the risk of fractures--FDA. Interim final rule.
AB - The Food and Drug Administration (FDA) is issuing this interim final rule to
prohibit the use on foods of a claim relating to the relationship between
calcium, bone density, and the risk of fractures. This interim final rule is in
response to a notification of a health claim submitted under section 303 of the
FDA Modernization act of 1997 (FDAMA). FDA is prohibiting the claim because
section 303 of FDAMA does not apply when FDA has an existing regulation
authorizing a health claim about the relationship between the nutrient and the
disease or health-related condition at issue. A health claim concerning the
relationship between calcium and osteoporosis is already authorized. As provided
for in section 301 of FDAMA, this rule is effective immediately upon publication.
PMID- 10180288
TI - Food labeling: health claims; chromium and the risk in adults of hyperglycemia
and the effects of glucose intolerance--FDA. Interim final rule.
AB - The Food and Drug Administration (FDA) is issuing an interim final rule to
prohibit the use on foods of a claim relating to the relationship between
chromium and the risk in adults of hyperglycemia and the effects of glucose
intolerance. This interim final rule is in response to a notification of a health
claim submitted under section 303 of the FDA Modernization Act of 1997 (FDAMA).
FDA has reviewed statements that the petitioner submitted in that notification,
and, in conformity with the requirements of FDAMA, the agency is prohibiting the
claim because the statements submitted as the basis of the claim are not
"authoritative statements" of a scientific body, as required by FDAMA; therefore,
section 303 of FDAMA does not authorize use of this claim. As provided for in
section 301 of FDAMA, this rule is effective immediately upon publication.
PMID- 10180289
TI - Food labeling: health claims; omega-3 fatty acids and the risk in adults of
cardiovascular disease--FDA. Interim final rule.
AB - The Food and Drug Administration (FDA) is issuing an interim final rule to
prohibit the use on foods of a claim relating to the relationship between omega-3
fatty acids and the risk in adults of cardiovascular disease. This interim final
rule is in response to a notification of a health claim submitted under section
303 of the FDA Modernization Act of 1997 (FDAMA). FDA has reviewed statements
that the petitioner submitted in that notification, and, in conformity with the
requirements of FDAMA, the agency is prohibiting the claim because the statements
submitted as the basis of the claim are not "authoritative statements" of a
scientific body, as required by FDAMA; therefore, section 303 of FDAMA does not
authorize use of this claim. As provided for in section 301 of FDAMA, this
interim final rule is effective immediately upon publication.
PMID- 10180290
TI - Food labeling: health claims; garlic, reduction of serum cholesterol, and the
risk of cardiovascular disease in adults--FDA. Interim final rule.
AB - The Food and Drug Administration (FDA) is issuing an interim final rule to
prohibit the use on foods of a claim relating to the relationship between garlic,
decreased serum cholesterol, and the risk in adults of cardiovascular disease.
This interim final rule is in response to a notification of a health claim
submitted under section 303 of the FDA Modernization Act of 1997 (FDAMA). FDA has
reviewed the statement that the petitioner submitted in that notification, and,
in conformity with the requirements of FDAMA, the agency is prohibiting the claim
because the statement submitted as the basis of the claim is not an
"authoritative statement" of a scientific body, as required by FDAMA; therefore,
section 303 of FDAMA, does not authorize use of this claim. As provided for in
section 301 of FDAMA, this rule is effective immediately upon publication.
PMID- 10180291
TI - Food labeling: health claims; zinc and the body's ability to fight infection and
heal wounds in adults--FDA. Interim final rule.
AB - The Food and Drug Administration (FDA) is issuing an interim final rule to
prohibit the use on foods of a claim relating to the relationship between zinc
and the body's ability to fight infection and heal wounds in adults. This rule is
in response to a notification of a health claim submitted under section 303 of
the FDA Modernization Act of 1997 (FDAMA). FDA has reviewed statements tht the
petitioner submitted in that notification, and, in conformity with the
requirements of FDAMA, the agency is prohibiting the claim because the statements
submitted as the basis of the claim are not "authoritative statements" of a
scientific body, as required by FDAMA; therefore, section 303 of FDAMA does not
authorize use of this claim. As provided for in section 301 of FDAMA, this rule
is effective immediately upon publication.
PMID- 10180292
TI - Food labeling: health claims; vitamin K and promotion of proper blood clotting
and improvements in bone health in adults--FDA. Interim final rule.
AB - The Food and Drug Administration (FDA) is issuing an interim final rule too
prohibit the use on foods of a health claim relating to relationships between
vitamin K and the promotion of proper blood clotting and improvement in bone
health in adults. This interim final rule is in response to a notification of a
health claim submitted under section 303 of the FDA Modernization Act of 1997
(FDAMA). FDA has reviewed the notification, and, in conformity with the
requirements of FDAMA, the agency is prohibiting the claim as a health claim
because the claim does not characterize the relationship of the nutrient vitamin
K to a disease or health-related condition, as required by section 303 of FDAMA;
therefore, section 303 of FDAMA does not authorize use of this claim as a health
claim. Although the claim is not a health claim, it may be the type of claim
permissible as a structure/function claim. As provided for in section 301 of
FDAMA, this rule is effective immediately upon publication.
PMID- 10180293
TI - Erythrityl tetranitrate; drug efficacy study implementation; revocation of
exemption; opportunity for a hearing--FDA. Notice.
AB - The Food and Drug Administration (FDA) is revoking the temporary exemption that
has allowed single-entity coronary vasodilator drug products containing
erythrityl tetranitrate to remain on the market beyond the time limits scheduled
for implementation of the Drug Efficacy Study. FDA is announcing that the
products lack substantial evidence of effectiveness and is offering an
opportunity for a hearing on a proposal to withdraw approval of any applicable
new drug applications (NDA's) or abbreviated new drug applications (ANDA's).
PMID- 10180294
TI - Statement of organization, functions, and delegations of authority--HCFA.
PMID- 10180295
TI - Medicare program; Medicare coverage of and payment for bone mass measurements-
HCFA. Interim final rule with comment period.
AB - This interim final rule with comment period provides for uniform coverage of, and
payment for, bone mass measurements for certain Medicare beneficiaries for
services furnished on or after July 1, 1998. It implements provisions in section
4106(a) of the Balanced Budget Act of 1997.
PMID- 10180296
TI - M.D. Physicians of Southwest Louisiana, Inc.; analysis to aid public comment-
FTC. Proposed consent agreement.
AB - The consent agreement in this matter settles alleged violations of federal law
prohibiting unfair or deceptive acts or practices or unfair methods of
competition. The attached Analysis to Aid Public Comment describes both the
allegations in the draft complaint that accompanies the consent agreement and the
terms of the consent order--embodied in the consent agreement--that would settle
these allegations.
PMID- 10180297
TI - Guidance of FDA's expectations of medical device manufacturers concerning the
year 2000 date problem--FDA. Notice.
AB - The Food and Drug Administration (FDA) is announcing the availability of the
guidance entitled "Guidance on FDA's Expectations of Medical Device Manufacturers
Concerning the Year 2000 Date Problem." The guidance, which is included in this
notice, is a Level 1 guidance that is immediately effective in accordance with
FDA's good guidance practices (GGP's) criteria, which allow immediate
implementation of guidance that is necessary for public health reasons. FDA will
receive comments on the guidance at any time and consider them in determining
whether to amend the current guidance.
PMID- 10180298
TI - Data watch. Patient care episodes in mental health organizations in 1955 and
1992.
PMID- 10180299
TI - Managing care with outcome data: new hopes, new responsibilities.
PMID- 10180300
TI - LTC-SPMI. Medicare's Operation Restore Trust. The role of effective
documentation.
PMID- 10180301
TI - How to involve staff in developing an outcomes-oriented organization.
AB - Outcomes management requires the active participation of clinical staff and/or
network providers to succeed. They form the bedrock of the system, since they are
the ones who most typically administer the outcomes assessment questionnaires to
consumers, encourage them to complete them, and respond to questions and
complaints about them. Resistance from clinicians can cause even the most well
designed outcomes management system to fail. Yet with the application of several
basic principles, organizations can maximize active participation from its
clinicians to operate a dynamic outcomes management system. The authors of this
article describe the principles involved, and the action steps necessary to
implement them. These principles include: articulate the value of the outcomes
management system, involve clinical staff in its design, make it relevant to
treatment goals, assure clinicians the system will not be used punitively, show
them how it will be used to improve treatment, obtain staff feedback routinely on
how the system is working, and demonstrate how the organizational culture from
top management down uses the outcomes information to make decisions.
PMID- 10180302
TI - Dialogue. Ethical and political issues in practice guidelines implementation.
PMID- 10180303
TI - Impact of managed care in the public sector: children and adolescents with
behavioral health problems and their families.
PMID- 10180304
TI - Strength-based assessment: the Behavioral and Emotional Rating Scale.
PMID- 10180305
TI - The indicator report.
PMID- 10180306
TI - Information technology and the chief executive.
PMID- 10180307
TI - How purchasers value behavioral health benefits. Interview by Tom Trabin.
PMID- 10180308
TI - Data security. Let your fingers do the talking.
PMID- 10180309
TI - XML (hypertext markup language) makes the Web as easy as ABC.
PMID- 10180310
TI - Carrying out a network vision. Interview by Tyler L. Chin.
PMID- 10180311
TI - Electronic records: key to HCFA compliance?
PMID- 10180312
TI - 1998 Market Leaders Report. Hardware and software market share based on a
national survey of integrated delivery systems.
PMID- 10180313
TI - Hot stocks. Stock market analysts explain which health care information
technology stocks earn their highest ratings--and why.
PMID- 10180314
TI - How are vendors fixing their year 2000 problems?
PMID- 10180315
TI - Physician profiling: using software to refine the art.
PMID- 10180316
TI - Provider automation. Placing a premium on education.
PMID- 10180317
TI - Slow pay and claims denials: welcome to the world of managed care.
AB - In markets heavily penetrated by managed care, case managers are facing a
disturbing trend: Health plans are denying claims at an alarming rate for what
many consider to be medically necessary care. Slow payment and increased scrutiny
of hospital utilization review also have been reported. In Maryland alone, the
state's largest insurer, Blue Cross and Blue Shield, denied $29 million in
hospital claims and 13% of all inpatient days in 1997, leading the state hospital
association to file a grievance alleging that BCBS and other insurers are denying
claims simply to cut costs. Experts argue that the trend toward claims denials
and slow payment is likely to increase the administrative burden of case managers
who perform utilization review, and could negatively affect patient care.
PMID- 10180318
TI - Plan of care ensures proper documentation.
AB - Via Christi Regional Medical Center in Wichita, KS, uses a plan of care form to
document patient care from pre-op to post-discharge, except for the
intraoperative phase. The comprehensive form ensures good note-taking, even from
traditionally poor documenters. A clinical pathway begins on page three of the
form and covers tests, treatment monitoring, prescriptions, activity, discharge
planning, nutrition, education, and consults for patients in partial day surgery,
pre-op and post-op, holding area surgery, and the post anesthesia care unit.
Potential problems areas for patients are documented in the following areas:
comfort, skin integrity, communication, psychosocial, safety, mobility,
physiological, and spiritual.
PMID- 10180319
TI - Don't shell out good money for bad education.
PMID- 10180320
TI - Integrate patient care with chemical dependency pathways.
PMID- 10180321
TI - AMI education cuts LOS, complications.
AB - A new report from the National Heart, Lung, and Blood Institute in Bethesda, MD,
concludes that reducing the length of time it takes patients to seek treatment
for symptoms of acute myocardial infarction (AMI) can reduce complications and
potentially lower inpatient length of stay. Factors that contribute to
prehospital delay include: older age, female gender, low socioeconomic status,
history of angina or diabetes, consulting a spouse or physician, and self
treatment. To reduce the likelihood of treatment delay among high-risk patients,
discharge planners should provide information about typical symptoms of AMI and
specific actions to take if symptoms occur. Education materials, written at a
sixth-grade level, should be used to reinforce the verbal message.
PMID- 10180322
TI - Competency programs help treat special populations.
PMID- 10180323
TI - Assessment system starts with new hire.
PMID- 10180324
TI - Industrial medical service a lucrative business source.
PMID- 10180325
TI - 1997: out with the old payment structures, in with the new.
PMID- 10180326
TI - Internal relationships affect a system's bottom line.
PMID- 10180327
TI - Some FIs (fiscal intermediaries) will be unable to process PPS claims until fall.
PMID- 10180328
TI - HCFA to include therapies and ambulance services in consolidated billing delay;
rule provides more details but questions remain.
PMID- 10180329
TI - Description of RUG III patient classification system in PPS rule incomplete,
possibly misleading.
PMID- 10180330
TI - HCFA predicts average SNF market basket index of 2.8 percent.
PMID- 10180331
TI - Wellness at work. Boost wellness center participation with target marketing
strategies.
AB - By using target marketing strategies, corporate wellness programs can increase
employee participation rates and tailor activities to meet employee needs. The
authors examined this issue through a research survey that segmented a
university's staff and employee population into three wellness program groups:
High Participators, Moderate Participators, and Low Participators. Participators'
views on the following issues were analyzed: health management programs, exercise
programs, wellness center use inhibitors, wellness center use incentives,
wellness center communications, and willingness to pay for the wellness center.
The results identified unique lifestyle characteristics for each group that can
help make target marketing strategies effective.
PMID- 10180332
TI - Direct-to-consumer ads can influence behavior. Advertising increases consumer
knowledge and prescription drug requests.
AB - This study examines the impact of direct-to-consumer (DTC) pharmaceutical
advertising on prescription drug knowledge and the requesting behavior of
consumers. The authors developed and tested a conceptual model of prescription
drug knowledge and requests. Consumers' belief that drug advertising can educate
them was associated with a greater amount of drug knowledge, and the belief they
would upset physicians by asking for specific drugs was associated with less
knowledge. The belief that drug advertising reduces prices was associated with
greater probability of drug requests, and the belief that physicians should be
the sole source of drug information was associated with lesser probability of
request. Preference for generic drugs was associated with a lesser likelihood of
requesting a specific drug. Media exposure and drug advertising awareness were
associated with higher drug knowledge and a greater probability of drug
requesting.
PMID- 10180333
TI - Marketing pharmaceutical products to physicians. Sales reps influence physicians'
impressions of the industry.
AB - A survey conducted at a large, Midwest teaching hospital provides a better
understanding of how marketing activities influence physicians' impressions of
the pharmaceutical industry; in particular, the extent to which physicians
believe that the pharmaceutical industry understands their needs and the extent
to which it is concerned about improving the overall quality of health in the
United States. Also, the authors explore the motivation of the pharmaceutical
industry: Is it primarily concerned with patients or with its own self-interest?
PMID- 10180334
TI - We're missing the boat in database marketing.
PMID- 10180335
TI - Marketing's role in hospital Web site development.
PMID- 10180336
TI - Reengineering the delivery of care.
PMID- 10180337
TI - Looking beyond the formulary budget in cost-benefit analysis.
AB - With the introduction of newer, more expensive psychotropic medications,
healthcare providers and managed care administrators must consider whether these
drugs offer "value for the money." A true picture of the benefits of these drugs
emerges only when all the costs of treatment are considered. Focusing exclusively
on the acquisition cost of the drug can result in a misleading impression of the
drug's worth. Although the medication costs associated with treating a patient
with a newer drug increase, use of these agents may actually result in an overall
decrease in healthcare costs, through reductions in hospitalization and length of
stay, use of mental health services, and prescriptions for adjunctive drugs. In
one study of the newer antipsychotic agent risperidone, the overall annual costs
of treating a patient with schizophrenia were reduced by nearly $8,000 (Canadian
dollars), even though medication costs increased by approximately $1,200
(Canadian dollars). Retrospective and prospective pharmacoeconomic studies can
provide valuable data on the cost effectiveness of treatment with newer
psychotropic medications.
PMID- 10180338
TI - Willingness to pay in the context of an economic evaluation of healthcare
programs: theory and practice.
AB - Cost-benefit analysis (CBA) is defined in the methodology literature as a form of
economic evaluation in which both costs and consequences are measured in monetary
terms. In recent years we have witnessed renewed enthusiasm for CBA and the use
of willingness to pay (WTP) as a method of measuring benefits from healthcare
providers. Using the economics perspective, this paper assesses the usefulness of
the WTP measure in a context of CBA analysis for economic evaluation of
healthcare interventions. Starting from the welfarist approach as the foundation
of the analysis, this paper evaluates the benefit and cost of using WTP as a
measure of outcome compared mainly with the most commonly used measure of outcome
(i.e., quality-adjusted life years) as well as a newly suggested measure of
outcome (i.e., healthy-years equivalents). This paper studies this issue from
both theoretical and practical aspects. The analysis starts with the premise that
we want to use the discipline of economics as the mode of thinking and evaluate
the methods suggested using economic criteria. A framework that includes five
indicators (or criteria) to help identify the measures of outcome that are proper
for use in the context of an economic evaluation are described. Following this
framework, the paper argues that from a theoretic perspective the WTP approach is
the best available measure, despite its limitations. This paper also describes a
new instrument that can be used to measure individuals' WTP as well as a recent
experience assessing the feasibility of using such an instrument in the context
of evaluating a new pharmaceutical agent in a managed care setting. The
conclusion of this study is that this technique holds promise as a method that
can generate monetary values for program benefits for future use in CBA.
PMID- 10180339
TI - A tale of two (or more) cities: geographic transferability of pharmacoeconomic
data.
AB - The economic evaluation of a new medicine often must be based on data gathered in
multiple countries. Because replication of trials is an expensive and inefficient
undertaking, analysts need to determine the validity of transferring cost
effectiveness data from one country to another. Threats to transferring data
involve differences among countries with regard to demography and epidemiology of
disease, clinical practice and conventions, incentives to and regulation of
healthcare providers, relative price levels, consumer preferences, and
opportunity cost of resources. Because of these differences, a drug can be cost
effective in one country and not cost-effective in another. Adapting a cost
effectiveness study conducted in one country to another country requires careful
scrutiny of the relevance of comparators, practice patterns, and relative price
weights.
PMID- 10180340
TI - Global health economics research: advanced concepts and use in the marketplace.
Papers based on Global Health Economics Summit held June 1996, in Toronto,
Canada.
PMID- 10180341
TI - Evaluating the cost effectiveness of newer psychotropic medications.
AB - With the introduction of newer, more expensive psychotropic medications,
pharmacists must consider the cost-effectiveness issues related to the use of
these drugs. In general, the newer agents are more effective than conventional
drugs, have improved side-effect profiles, and are associated with a lower rate
of recidivism. However, because of cost constraints, not every patient who needs
a newer psychotropic drug has the opportunity to receive it. To provide these
patients with the medication they need, we must look beyond the acquisition cost
of the drug and focus on the global impact of the medication on the total mental
health budget at a facility. Data from this point of view can justify the greater
expense of the medication, and more importantly, the patient can be better
served. Cost-effectiveness data from one's own institution may be more convincing
to formulary committee members than data from academic centers and can help make
newer, more expensive agents available to the patients who need them. Designing
and implementing a retrospective study is one means of obtaining these cost
effectiveness data.
PMID- 10180342
TI - Preferences for health outcomes and cost-utility analysis.
AB - Economic evaluation of health programs consists of the comparative analysis of
alternative courses of action in terms of both costs and consequences. The five
analytic techniques are cost-consequence analysis, cost-minimization analysis,
cost-effectiveness analysis, cost-utility analysis, and cost-benefit analysis.
Although all techniques have the same objective of informing decision making in
the health programs, they come from different theoretic backgrounds and relate
differently to the discipline of economics. Cost-utility analysis formally
incorporates the measured preferences of individuals for the health outcome
consequences of the alternative programs. The individuals may be actual patients
who are experiencing or have experienced the outcomes, or they may be a
representative sample of the community, many of whom may someday face the
outcomes. The health outcomes, at the most general level, consist of changes in
the quantity and quality of life; that is, changes in mortality and morbidity.
Changes in quantity of life are measured with mortality; changes in quality of
life are measured with health-related quality-of-life instruments. Utilities
represent a particular approach to the measurement of health-related quality of
life that is founded on a well specified theory and provides an interval scale
metric. Changes in quantity of life, as measured in years, can be combined with
changes in quality of life, as measured in utilities, to determine the number of
quality-adjusted life years gained by a particular health program. This can be
compared with the incremental cost of the program to determine the cost per
quality-adjusted life-year gained. Utilities may be measured directly on patients
or other respondents by means of techniques such as visual analog scaling,
standard gamble, or time trade-off. Utilities may be determined indirectly by
means of a preference-weighted multi-attribute health status classification
system such as the health utilities index. The health utilities index is actually
a complete system for use in studies. It consists of questionnaires in various
formats and languages, scoring manuals, and descriptive health status
classification systems. The health utilities index is useful in clinical studies
and in population health surveys, as well as in cost-utility analyses.
PMID- 10180343
TI - Clinical and economic considerations of coronary heart disease: a managed care
approach. Proceedings based on presentations from two conferences, Cardiovascular
Event Reduction: Defining the Role of HMG Therapy in Managed Care, held November
14-16, 1997 in Philadelphia, and Pharmacoeconomics & Outcomes Issues of Lipid
Therapy, held November 5-7, 1997 in Orlando.
PMID- 10180344
TI - Assessing the value and affordability of cholesterol reduction in the managed
care setting.
PMID- 10180345
TI - Express unit propels hospital to stellar benchmarking performance.
PMID- 10180346
TI - Discharge-to-bill drop time is 24 to 48 hours.
PMID- 10180347
TI - Magnet Awards recognize best nursing practices.
PMID- 10180348
TI - Special report: mining admissions data. Benchmark admissions identify areas for
improvement.
PMID- 10180349
TI - 1998 GHA. Distinguished Service Awards. Damon D. King, Dr. Clarence C. Butler.
PMID- 10180350
TI - Antitrust update: recent legal developments for merging hospitals.
PMID- 10180351
TI - GHA'S TELNET expands to other states; South Carolina and Virginia first to sign
on.
PMID- 10180352
TI - An American tragedy.
PMID- 10180353
TI - Fast-track protocol targets high-cost, high-volume cases.
PMID- 10180354
TI - St. Joseph teams up wih EPA for big energy savings.
AB - U.S government to the rescue? An energy savings program with the U.S
Environmental Protection Agency is saving big bucks for plenty of health care
facilities around the country. A good example is St. Joseph Hospital in
Lancaster, PA, which is saving an estimated $175,000 each year from new lighting
fixtures alone. And that's just the beginning. Here's the story, plus details on
how you can tap into this voluntary program.
PMID- 10180355
TI - Ongoing data monitoring, accountability as important as reengineering itself.
AB - After your reengineering success: Don't just sit there! What happens after a
process redesign program ends can be just as important as the reengineering
effort itself. Just ask officials at this New Jersey facility. Despite a whopping
$4 million in savings derived from a major redesign of patient care service
delivery, administrators and managers are working just as hard at keeping
everyone on their toes with an ongoing monitoring and accountability process.
Learn how important those efforts can be to ensuring continued success long after
the formal reengineering process is completed.
PMID- 10180356
TI - New comparative performance study shows hospitals struggle with growing operating
costs.
AB - Data Benchmarks: Trouble keeping expenses in check? You're not alone. A newly
released study of hospital financial data shows hospitals nationwide continue
their struggle to keep operating expenses down. Despite continued increases in
median operating revenues at many hospitals, they are having a tough time keeping
a lid on expenses in many categories. How does your organization compare? Here
are the details.
PMID- 10180357
TI - New pre-op functions cut costs and boost revenues.
PMID- 10180358
TI - Oncology provider's disease management program targets hospital care for savings.
AB - Capitated provider saves more than $100,000 in first year of disease management
program for cancer care: Although the actual patient numbers are low, cancer care
consumes a disproportionate amount of resources. That's why this New Hampshire
based multispecialty group practice and affiliated hospital targeted cancer cases
for disease management. Here are the details on how this aggressive program
works, along with key areas of cancer care that reap the greatest cost
efficiencies and some interesting costs data.
PMID- 10180359
TI - Focus on high-volume procedures for greatest cost savings, finds new study.
AB - Data Benchmarks: Target high-volume procedures for greatest impact. A new study
demonstrates the potential for cost savings and reductions in length of stay for
65 inpatient surgical procedures. The study, based on Medicare surgical data,
ranks the top procedures with highest potential for savings, looks at the
influence of managed care penetration in the marketplace, and offers national and
regional benchmark comparisons. Here are the details and data.
PMID- 10180360
TI - Houston cancer center improves productivity, saves big with reengineered info
system.
AB - Reengineer information systems the right way: Integrating disparate software
programs is no small feat when complex webs of systems need to be dismantled and
redesigned. That's what The University of Texas M.D. Anderson Cancer Center in
Houston discovered when reengineering its information systems within the
facilities management department. The painstaking effort has already begun paying
off, with improvements in productivity and savings on inventory. Learn how M.D.
Anderson expects to save more than $100,000 a year with this new system.
PMID- 10180361
TI - Reluctant rationers: public input to health care priorities.
AB - Members of the public can adopt any one of at least three roles when providing
input to public decision-making: taxpayer, collective community decision-maker,
or patient. Each of these potential roles can be mapped onto three areas of
public policy decision-making in health care: funding levels and organization for
the system, the services we choose to offer under public funding, and the
characteristics of those who should receive the offered services. The increasing
desire to involve the public across the spectrum of health care decision-making
has yet to result in a clear delineation of either which of the areas are most
appropriate for public input or which of the roles we wish individual
participants to adopt. The average citizen (as opposed to the self-interested
patient, the provider or the manager) has so far shown little interest in
contributing and rarely has the requisite skills for most of the tasks asked of
him or her. The widespread motivation of governments and others for seeking
public input appears to be to get the public to take or share ownership in the
tough rationing choices consequent on fiscal retrenchment in health care.
Evaluation of existing literature leads to the conclusion that there are only
limited areas where we might wish to obtain significant public input if we adopt
this widespread policy motivation. Specifically, the general public should be
asked to give input to, but not determine, priorities across the broad service
categories that could potentially be publicly funded. Members of the public have
neither the interest nor the skills to do this at the level of specific services.
The role expected of such members of the public should be made explicit and
should focus on collective views of the community good rather than self
interested views of individual benefit. Groups of patients, however, should be
the source of input when socio-demographic characteristics are being used to
decide who should receive offered services. The role expected of these consumers
is not, however, to take a self-interested perspective; rather, it is to adopt
Rawls' 'veil of ignorance' to reflect compassionate views of priorities across
socio-demographic characteristics. Finally, there appears to be no best method
for obtaining public input that overcomes the common problems of poor information
upon which to base priorities, difficulty in arriving at consensus, poor
representativeness of participants, and lack of opportunity for informed
discussion prior to declaring priorities. There is some suggestion, however, that
panels of citizens or patients, convened on an ongoing basis and provided with
the opportunity to acquire relevant information and discuss its implications
prior to making consensus recommendations, offer the most promising way forward.
PMID- 10180362
TI - Partnerships with patients: the pros and cons of shared clinical decision-making.
AB - The traditional style of medical decision-making in which doctors take sole
responsibility for treatment decisions is being challenged. Attempts are being
made to promote shared decision-making in which patients are given the
opportunity to express their values and preferences and to participate in
decisions about their care. Critics of shared decision-making argue that most
patients do not want to participate in decisions; that revealing the
uncertainties inherent in medical care could be harmful; that it is not feasible
to provide information about the potential risks and benefits of all treatment
options; and that increasing patient involvement in decision-making will lead to
greater demand for unnecessary, costly or harmful procedures which could
undermine the equitable allocation of health care resources. This article
examines the evidence for and against these claims. There is considerable
evidence that patients want more information and greater involvement, although
knowledge about the circumstances in which shared decision-making should be
encouraged, and the effects of doing so, is sparse. There is an urgent need for
more research into patients' information needs and preferences and for the
development and evaluation of decision-support mechanisms to enable patients to
become informed participants in treatment decisions.
PMID- 10180363
TI - Comparing health care systems: how do we know if we can learn from others?
PMID- 10180364
TI - Experience in Manitoba with a population-based health information system.
PMID- 10180365
TI - The media and the scientific message.
PMID- 10180366
TI - Rationing health care: a national framework and local discretion.
PMID- 10180367
TI - Did the introduction of general practice fundholding change patterns of emergency
admission to hospital?
AB - OBJECTIVES: To test the hypothesis that the introduction of general practice
fundholding was associated with a change in the proportion of emergency
admissions to hospital. METHODS: Before and after natural experiment with control
group. The experimental group was first-wave fundholding general practices in the
South Western Regional Health Authority, the control group was all practices that
remained non-fundholding as of April 1993. Data were collected on episodes of
care in hospitals in the South Western region involving cholecystectomy, hernia
repair, intervertebral disc operation and prostatectomy. The additional impact of
fundholding status on any underlying changes in proportions of emergency
admissions was examined using multiple logistic regression. RESULTS: There was no
evidence of an interaction between fundholding status and before/after time
period. Odds ratios and confidence intervals for the interaction of general
practice fundholding status and time were: prostatectomy 1.02 (0.77 to 1.34);
hernia repair 0.94 (0.7 to 1.24); intervertebral disk operations 1.67 (0.8 to
3.47); prostatectomy 0.94 (0.69 to 1.27). CONCLUSIONS: The results provide no
evidence that, in the first 2 years of the scheme, fundholding had an impact on
the proportion of emergency admissions to hospital.
PMID- 10180368
TI - The relationship between the supply of cardiac catheterization laboratories,
cardiologists and the use of invasive cardiac procedures in northern New England.
AB - OBJECTIVES: Utilization rates of coronary angiography and cardiac
revascularization have been found to vary between areas. This study addresses the
relationship between resource supply and procedure rates. METHODS: We compared
the association of per capita catheterization laboratories, per capita
cardiologists and multi-provider markets (where more than one hospital offers
coronary angiography services) with the utilization rates for angiography and
cardiac revascularization in northern New England, USA. Administrative data were
used to capture invasive cardiac procedures. Small area analyses were used to
create coronary angiography service areas. Linear regression methods were used to
measure associations between the resource supply and utilization rates. RESULTS:
Variation in the use of invasive cardiac procedures was strongly associated with
the population-based availability of catheterization facilities and multi
provider markets and unrelated to cardiologist supply or need (as reflected in
the hospitalization rates for myocardial infarction). In the multivariate model,
an increase of 1 catheterization laboratory per 100,000 population was associated
with an increase in the angiography rate of 1.62 per 1000 population; those
service areas with multi-provider markets were associated with an additional
increase in the angiography rate of 1.27 per 1000 population (R2 = 0.84, P =
0.0006). There was a moderately strong relationship between the catheterization
laboratories per capita and the revascularization rates (R2 = 0.43, P = 0.029).
Angiography rates were highly associated with cardiac revascularization rates: an
increase in the angiography rate of 1 per 1000 population was associated with a
0.46 per 1000 increase in the cardiac revascularization rate (R2 = 0.85, P =
0.0001). CONCLUSIONS: Our work suggests that current efforts to address variation
in cardiac procedures through activities such as appropriateness criteria,
guidelines and utilization review are misdirected and should be redirected
towards capacity, in this case the supply of catheterization facilities.
PMID- 10180369
TI - Unequal randomisation can improve the economic efficiency of clinical trials.
AB - OBJECTIVES: In the majority of clinical trials patients are randomised equally
between treatment groups. This approach maximises statistical power for a given
total sample size. The objectives of this paper were to determine if, when
research costs between treatments differ, it is more economically efficient to
randomise additional patients to the cheaper treatment, and how the optimum
randomisation ratio can be estimated. METHODS: Estimation of the most
economically efficient randomisation ratio for four hypothetical clinical trials
using cost-effectiveness analysis. RESULTS: When research costs differ between
treatments, and there is no constraint on total sample size, it is always more
cost-effective to randomise more patients to the cheaper treatment. For example,
a cost ratio between the lesser and more expensive treatment of ten, results in a
randomisation ratio of 3.2:1. CONCLUSIONS: Unequal randomisation ratios should be
more widely used as this will achieve optimum statistical power for the lowest
expenditure of research resources.
PMID- 10180370
TI - Integrating mental health services through reimbursement reform and managed
mental health care.
AB - People with serious and persistent mental illness require a range of community
services typically provided by different specialized agencies. At the clinical
level, assertive team case management is the strategy commonly used to achieve
integration of services across specialized sectors. The USA also has used various
financial and organizational approaches to reduce fragmentation and increase
effectiveness, including development of stronger public mental health
authorities, use of financial incentives to change professional and institutional
behavior, requirements to allocate savings from hospital closures to community
systems of care, and introduction of mental health managed care on a broad scale.
These approaches have potential but also significant problems and there is often
a large gap between theory and implementation. These US developments are
discussed with attention to the implications for mental health services in the
UK.
PMID- 10180371
TI - Socio-economic status and visits to physicians by adults in Ontario, Canada.
AB - OBJECTIVES: To examine the association between socio-economic status, need for
medical care and visits to physicians in a universal health insurance system.
METHODS: Cross-sectional analysis of the 1990 Ontario Health Survey, a population
based survey utilizing a multi-stage, randomized cluster sample. The analysis
considered only those respondents who were 16 years of age or older from the
province of Ontario, Canada: 21,272 males and 24,738 females. RESULTS: There was
no difference by education or income in persons having made at least one visit to
a general practitioner in the previous year. High income persons were less likely
to have made six or more visits to a general practitioner--odds ratio (OR) =
0.67, 95% CI = 0.52, 0.87 for men; OR = 0.66, 95% CI = 0.58, 0.75 for women--but
more likely to have made at least one visit to a specialist--OR = 1.42, 95% CI =
1.15, 1.76 for men; OR = 1.25, 95% CI = 1.07, 1.45 for women. A person's need for
medical care was the most important determinant of a physician visit.
CONCLUSIONS: Self-reported visits to general practitioners in Canada are strongly
influenced by a person's need for medical care and are appropriately related to
socio-economic status. However, there is a residual association between higher
socio-economic levels and greater use of specialist services.
PMID- 10180372
TI - Can't pay, won't pay? Finance for long-term care.
PMID- 10180373
TI - Psychological and managerial aspects of the scientist and the research team.
PMID- 10180374
TI - Geographic variation in the utilization and choice of procedures for treating
coronary artery disease in New York State. Ischaemic Heart Disease Patient
Outcomes Research Team (PORT).
AB - OBJECTIVES: To examine geographical variations in rates of coronary artery bypass
grafting (CABG) and percutaneous transluminal coronary angioplasty (PTCA) in New
York State, and to examine variations in the choice between these two procedures.
METHODS: A retrospective analysis of data from the New York registries for CABG
and angioplasty was conducted. Rates were compared for 12 different regions of
the state to assess geographic variations. To assess variations in the choice of
procedure, frequencies of each procedure by region were compared with expected
frequencies obtained by a logistic regression model that related procedure
performance to various patient risk factors. RESULTS: There was more than a three
fold variation in age/sex adjusted CABG rates and more than a two-fold variation
in age/sex adjusted angioplasty rates among regions. The regional percentages of
patients undergoing CABG rather than PTCA ranged from 49% to 70%, and most of the
disparity was not related to patient risk factors. Instead, the disparity was
largely a result of differences in racial composition and the hospitalization
rate for myocardial infarctions. CONCLUSIONS: There is considerable regional
variation in New York in the tendency to use aggressive cardiac procedures and in
the choice of which procedure to use, and these differences are mostly unrelated
to patient need.
PMID- 10180375
TI - Models of hospital drug policy in the UK.
AB - OBJECTIVES: Pharmacists in UK National Health Service (NHS) hospitals have a long
tradition of involvement in the development of drug policy. This paper describes
various approaches that have been employed in the development and implementation
of drug policy in hospitals and examines the evidence for their effectiveness and
acceptability in the context of a changing health service. METHODS: A series of
focused interviews was conducted with a range of staff, including doctors,
nurses, pharmacists and managers at eight hospitals. Interview sites were
selected on the basis of a national survey of clinical pharmacy roles and were
broadly representative of UK NHS hospitals. Interview data were analysed using
constant comparison and analytic induction. RESULTS: Three models used in the
development of drug policy were identified: a 'traditional' model, in which a
drug and therapeutics committee establishes a hospital-wide formulary which is
implemented by pharmacists; a 'combined' model, in which there is much more
emphasis on tailoring policies and feedback to specialties or clinical
directorates; and a 'medical control' model, in which prescribing decisions are
made by individual doctors without reference to explicit policies and with little
active pharmacy involvement. Pharmacy involvement was seen as vital to the
development of effective policies but hospital-specific factors influenced the
choice of model at particular sites. CONCLUSIONS: Hospitals may be moving towards
the 'combined' model which could have advantages in the current internal market
within the NHS. However, evaluations of the various approaches to drug policy
should help inform this decision.
PMID- 10180376
TI - Informing prescribing allocations at district level in England.
AB - OBJECTIVES: To derive a predictive model based on the morbidity, demographic and
socio-economic characteristics of district populations to explain variations in
prescribing costs in England. METHOD: Inter-relations between morbidity,
demographic, socio-economic, general practice supply characteristics and net
ingredient cost per age, sex and temporary resident originated prescribing unit
(ASTRO-PU) were explored statistically for 90 districts in England using 1994
cost data. The possibility of mutual inter-relationship between 'supply' and
'demand' was examined; then the associations between a range of factors and
prescribing costs were estimated using ordinary least squares regression and the
predictive power of the possible models was systematically examined. RESULTS:
Whilst there was a relatively weak relationship between the supply factors that
were measured, there did not appear to be any reciprocal relationship. Three
parsimonious models estimated using ordinary least squares multiple regression
techniques based on combinations of permanent sickness, low birth weight and the
proportion of general practitioners registered for postgraduate certificate of
education were identified. The models explained up to 61% of variation between
districts in prescribing costs. CONCLUSIONS: 'Need' and 'supply' characteristics
are independently associated with variations in prescribing costs at district
level. The negative association between the proportion of general practitioners
eligible for postgraduate education allowance and prescribing costs may reflect
'better' prescribing but could not be introduced into a resource allocation
formula without introducing perverse incentives. The combination of permanent
sickness and low birth weight complement each other by providing a proxy measure
of morbidity mostly applicable to adult males (permanent sickness) and mothers
(low birth weight being a measure of maternal health). These variables should be
considered further for use in the process of allocating resources for prescribing
to districts.
PMID- 10180377
TI - Aggregating health state valuations.
AB - It is now recognized that preference-based measures of health status have an
important role to play in determining priorities in health care. A number of
methodological and ethical issues have been raised, but one that has as yet
received little attention is the question of how individual responses should be
aggregated when attempting to express the valuations of a given group. In a
recent study of over 3000 members of the British general public, valuations were
elicited for health states defined in terms of the EuroQol Descriptive System
using the time trade-off method. A EuroQol 'tariff' of valuations has been
generated which, because of the methodology employed, provides a good
approximation of mean values. The purpose of this paper is to present a tariff
based on median values. The nature of the distributions of values results in a
median-based tariff which, compared to the mean-based one, has higher values for
less severe states and lower values for more severe states. This is likely to
have important implications for resource allocation decisions.
PMID- 10180378
TI - Organ transplantation and European Community law: the case of non-residents.
AB - OBJECTIVES: The role of the European Union in influencing health care policies in
member states is of increasing importance. The Eurotransplant Foundation is an
organization which provides donor organs to the most suitable transplant
recipients. It covers a region of five countries (Austria, Belgium, Germany,
Luxembourg, The Netherlands). As there is a severe shortage of donor organs
within its region, registration of so-called non-resident patients on the waiting
lists aggravates this shortage. Could European Community law, especially rules on
competition, limit Eurotransplant's freedom to introduce a restrictive policy on
non-residents? If so, could participating transplant centres or patients initiate
legal action against Eurotransplant to stop the execution of such a policy?
METHODS: Quantitative descriptive data on organ donation and use by the
Eurotransplant Foundation during 1994 and 1995, by residents and non-residents.
Analysis on basis of economic and legal framework. RESULTS: Solidarity between
potential donors and potential recipients is organized in a different manner in
an organization such as Eurotransplant as compared to a national organization
under national law. National regulations may introduce a restrictive policy for
the acceptance of non-resident patients. Eurotransplant--as a matter of its own
policy--has to consider international solidarity. The scope of the non-resident
issue is dealt with, and it is explained why it is considered to be a problem. On
the basis of a discussion of the economic and the legal framework for a non
resident policy, an answer to the question is suggested. CONCLUSION: It might be
possible for Eurotransplant to introduce a restrictive policy on the admission of
non-residents without violating the European Community Treaty.
PMID- 10180379
TI - The efficiency of specialist outreach clinics in general practice: is further
evaluation needed?
AB - OBJECTIVES: To assess the need for further evaluation of general practice-based
outreach clinics in two specialties using data from a UK pilot study to model
their cost-effectiveness. METHODS: A pilot study was undertaken comparing one
outreach and one outpatient clinic held by three dermatology specialists and
three orthopaedic specialists. Information was collected on waiting times, costs
to patients, casemix and resource use. RESULTS: Only dermatology outreach clinic
patients experienced significantly shorter waiting times for first appointments
than their hospital counterparts. Outreach clinic patients incurred lower costs
in attending appointments in either specialty but the differences were not
statistically significant. Evidence of a difference in casemix between patients
attending outreach and outpatient clinics meant that treatment costs incurred in
both types of clinic could not be compared. Outreach clinics in both specialties
were significantly more costly in terms of staff, staff travel and associated
opportunity costs compared with outpatient clinics. Sensitivity analysis showed
that outreach and outpatient clinics had the same marginal cost if the number of
patients per outreach clinic increased greatly or attendance fell considerably at
outpatient clinics. CONCLUSIONS: This study has found no evidence that outreach
clinics in these two specialties are cost-effective in terms of costs and
benefits. A more definitive conclusion could only be made if studies estimated
other costs and benefits not accounted for in this study. Further research is
required to see whether outreach clinics in other specialties or clinics with
different configurations to those studied are efficient.
PMID- 10180380
TI - Large-scale organizational and managerial change in health care: a review of the
literature.
AB - This paper takes an overview of the organizational and managerial literature on
recent large-scale change efforts within health care organizations. Such
literature refers to issues of enhanced policy significance, as a succession of
such changes has swept through health care, at an international level.
Interpretive and case study method have been widely employed in this field. While
the literature is emergent, key empirical concerns can be identified: (1)
Changing roles and relationships, with the rise of management and the challenge
to clinical domination; some argue that radical deprofessionalization now is
evident, while others take a more nuanced view. (2) The impact of marketization,
with health care becoming more of a commodity; various models of a health care
'quasi market' have been formulated. (3) Understanding the process of change in
health care organizations, such as the development of a management of change
literature. New theoretical frameworks have been developed, notably 'the reform
cycle' as a way of understanding progressive cycles of organizational reform, the
impact on health care of the rise of the new public management, and examining the
demedicalization thesis through the more generic literature on professions. The
paper concludes with a discussion of what this research base could contribute to
policy-making.
PMID- 10180381
TI - Nursing, knowledge and practice.
AB - Recent commentators have suggested that academic knowledge is irrelevant to
nursing practice and may actually undermine nursing's traditional caring ethos.
Furthermore, by making nursing more academic, it is claimed that 'natural' but
non-academic carers are prevented from pursuing a career in nursing. Debates
about the relationship between nursing, knowledge and practice have a long
history and have to be understood in terms of wider political and economic issues
relating to nursing, its status within society and the changing role of nurses
within the health services division of labour. One crucial issue is nursing's
status as women's work. Critics of developments in nurse education draw an
ideological equation between nursing work and the traditional female role. From
this perspective the qualities that make a good nurse cannot be taught, rather
they are founded on 'natural' feminine skills. Irrespective of whether caring is
'natural' or not, it is questionable as to whether, for today's nurses, being
caring is sufficient. The shape of nursing jurisdiction is a long way removed
from its origins in the Victorian middle-class household. In addition to their
traditional caring role, contemporary nurses may also have complex clinical,
management and research responsibilities, as well as being crucial coordinators
of service provision. It is suggested that these and future developments in
health services make the need for an educated nursing workforce even more
pressing. In order to adequately prepare nurses for practice, however, it is
vital that nurse education reflects the reality of service provision.
PMID- 10180382
TI - A competitive approach to saving universal health care.
PMID- 10180383
TI - Not a 'proper' solution? The gap between professional guidelines and users' views
about the safety of using emergency contraception.
AB - OBJECTIVES: As a form of contraception which is used after sex, emergency
contraception occupies a singular place in the birth control repertoire. The
relatively high UK incidence of pregnancy terminations and of teenage pregnancy,
combined with the recognition that much early sex remains unplanned and
unprotected, has led to calls for better access to emergency contraceptive
methods. In this study a combination of self-completion questionnaires and semi
structured interviews was used to explore views of emergency contraception among
women who were using the method. METHODS: Five hundred and ten women attending
two family planning clinics in Oxford and London completed a questionnaire in the
waiting room and 53 women who were attending for emergency contraception took
part in semi-structured interviews. RESULTS: The view, presented in recently
published UK guidelines, that emergency contraception is a reliable method and
not dangerous to repeat, was not shared by the respondents. The rationale for and
sources of women's concerns about the strength of the dose of hormonal emergency
contraception and the nature of side-effects are explored.
PMID- 10180384
TI - Shifting finance out of acute hospitals.
PMID- 10180385
TI - Private provision of 'outreach' clinics to fundholding general practices in
England.
AB - OBJECTIVES: To establish the contribution of the private sector in providing
outpatient 'outreach' clinics in general practitioner fundholding practices.
METHOD: Postal survey of all 13 first-wave fundholders and four of the 13 second
wave fundholders in the former South East Thames Region of the National Health
Service in 1995. RESULTS: Fourteen practices responded. Ten practices had set up
at least one medical specialist 'outreach' clinic and 12 at least one paramedical
clinic since becoming fundholders. Eight practices reported their arrangements
for consultant 'outreach' clinics and ten practices their arrangements for
paramedical clinics. Forty-nine per cent of the total medical specialist hours
and 46% of total paramedical hours were provided by private practitioners. The
largest number of hours provided privately was in gynaecology. CONCLUSION: This
small study identified considerable private provision of fundholders' 'outreach'
clinics. However, there is no system in the NHS to monitor the extent of this
market, the types of activities undertaken or the relative quality and cost of
the services provided.
PMID- 10180386
TI - Micro-level analysis of distributional changes in health care financing in
Finland.
AB - OBJECTIVES: In the early 1990s the Finnish economy suffered a severe recession at
the same time as health care reforms were taking place. This study examines the
effects of these changes on the distribution of contributions to health care
financing in relation to household income. Explanations for changes in various
indicators of health care expenditure and use during that time are offered.
METHOD: The analysis is based partly on actual income data and partly on
simulated data from the base year (1990). It employs methods that allow the
estimation of confidence intervals for inequality indices (the Gini coefficient
and Kakwani's progressivity index). RESULTS: In spite of the substantial decrease
in real incomes during the recession, the distribution of income remained almost
unaltered. The share of total health care funding derived from poorer households
increased somewhat, due purely to structural changes. The financial plight of the
public sector led to the share of total funding from progressive income taxes to
decrease, while regressive indirect taxes and direct payments by households
contributed more. CONCLUSIONS: It seems that, aside from an increased financing
burden on poorer households, Finland's health care system has withstood the
tremendous changes of the early 1990s fairly well. This is largely attributable
to the features of the tax-financed health care system, which apportions the
effects of financial and functional disturbances equitably.
PMID- 10180387
TI - Were practice nurses distributed equitably across England and Wales, 1988-1995?
AB - OBJECTIVE: To examine whether variations in the number of whole-time equivalent
(wte) practice nurses across family health services authorities (FHSAs) can be
explained by population characteristics and the organisation of general practice.
METHODS: Analysis of nine health and 16 social indicators for 98 FHSAs identified
three factors underlying health care needs. These factors and seven practice
characteristics were analysed by stepwise regression. A formula for allocating
health care resources and a logistic growth model were used to estimate the
'expected' number of nurses. RESULTS: Past trends indicate an eventual (wte)
practice nurse workforce of 12,500 (95% CI +/- 3500). Although geographical
disparities have declined, there was a two-fold variation in nurse numbers across
FHSAs. Around 2000 (wte) posts would be required to bring under-provided areas,
mostly in northern England and metropolitan districts, up to the highest level of
provision. There were more nurses in areas with higher proportions of elderly
people but fewer where deprivation, morbidity and mortality levels were above
average. The number of general practitioners was the most significant predictor
of practice nurse provision (t = 5.0); population needs and practice
characteristics explained 24% of the variation. CONCLUSIONS: The distribution of
practice nurses scarcely corresponded with health care needs at the FHSA level.
Despite a lack of evidence that nurses are a cost-effective addition to the
primary health care team, their role and numbers will be driven by the extent to
which they take on responsibilities performed by doctors. Achieving equity in
practice nurse provision probably requires explicit consideration in a formula
for allocating primary care funds, backed by audit of the services they provide.
PMID- 10180388
TI - The importance of laboratory data for comparing outcomes and detecting 'outlier'
wards in the treatment of patients with pneumonia.
AB - OBJECTIVES: To evaluate whether routine laboratory data can improve the ability
to compare risk-adjusted outcomes of different medical wards, and to detect
'outlier' wards with significantly better or worse outcome. METHODS: Patient data
were taken from the Combined Patient Database Systematic Management and Research
Tool, a database created by merging different computerized sources at a tertiary
care hospital. All patients admitted to internal wards with the diagnosis of
pneumonia during the years 1991-1995 were included (n = 2734). The outcome
variable was mortality 30 days post-admission. We used three comorbidity measures
based on ICD-9-CM codes as possible predictors of mortality: secondary diagnoses;
the Health Care Financing Administration severity index; and the Charlson
comorbidity index. Models were created using logistic regression. To each model,
laboratory data gathered in the first 48 hours after admission were added. To
identify 'outlier' services we determined whether the patients' ward was an
independent predictor of mortality. The area under the receiver operator curve
(ROC) of the models was used for comparisons. RESULTS: The area under the ROC was
0.65-0.72 for the models based on age and comorbid diagnoses. The addition of
laboratory data improved markedly the discriminatory ability of each of the
models, as reflected by an increase in the area under the ROC to 0.83-0.84. An
'outlier' ward with a higher risk-adjusted mortality rate was identified only by
the models that included laboratory data. CONCLUSION: Basic, automated, routinely
gathered laboratory data added significantly to the discriminatory power of risk
models based on administrative data with abstracted diagnoses. Addition of
laboratory data improved the ability to identify providers with possible
exceptional quality of care.
PMID- 10180389
TI - The 'number needed to treat' and the 'adjusted NNT' in health care decision
making.
AB - Within 'evidence-based medicine and health care' the 'number needed to treat'
(NNT) has been promoted as the most clinically useful measure of the
effectiveness of interventions as established by research. Is the NNT, in either
its simple or adjusted form, 'easily understood', 'intuitively meaningful',
'clinically useful' and likely to bring about the substantial improvements in
patient care and public health envisaged by those who recommend its use? The key
evidence against the NNT is the consistent format effect revealed in studies that
present respondents with mathematically-equivalent statements regarding trial
results. Problems of understanding aside, trying to overcome the limitations of
the simple (major adverse event) NNT by adding an equivalent measure for harm
('number needed to harm' NNH) means the NNT loses its key claim to be a single
yardstick. Integration of the NNT and NNH, and attempts to take into account the
wider consequences of treatment options, can be attempted by either a 'clinical
judgement' or an analytical route. The former means abandoning the explicit and
rigorous transparency urged in evidence-based medicine. The attempt to produce an
'adjusted' NNT by an analytical approach has succeeded, but the procedure
involves carrying out a prior decision analysis. The calculation of an adjusted
NNT from that analysis is a redundant extra step, the only action necessary being
comparison of the results for each option and determination of the optimal one.
The adjusted NNT has no role in clinical decision-making, defined as requiring
patient utilities, because the latter are measurable only on an interval scale
and cannot be transformed into a ratio measure (which the adjusted NNT is implied
to be). In any case, the NNT always represents the intrusion of population-based
reasoning into clinical decision-making.
PMID- 10180390
TI - League tables for performance improvement in health care.
AB - OBJECTIVES: Increasingly health care performance data are being disseminated in
the form of 'league tables' of health care providers, with the implication that
such publication helps purchasers select the better providers, and spurs
providers into improvements. This paper examines progress to date. METHODS: Three
stages of the league table process are considered: measurement, analysis and
action. RESULTS: A wide range of measurement schemes are now in place, although
the emphasis has been on process variables and mortality as a measure of outcome.
Several analytical techniques have been deployed to help users make sense of
league tables, and to help determine the causes of variations in reported
performance. The weakest aspect of current methods relates to the use to which
such analysis is put. CONCLUSIONS: A haphazard approach to using league table
data exists, with few reports on the impact of publication. A variety of
directions for future research into the use of performance data are needed.
PMID- 10180391
TI - Rationing in health care.
PMID- 10180392
TI - Computer simulation to estimate the effectiveness of carotid endarterectomy.
AB - OBJECTIVES: To investigate the benefit of carotid endarterectomy relative to
medical treatment, by comparing the outcome for different groups of patients
following transient ischaemic attacks. METHODS: A Markov model was used to
describe the survival and quality of life of patients treated for a transient
ischaemic attack. The benefit is measured in terms of quality adjusted life
months (QALMs). The outcome was estimated using a computer simulation with
parameters based on published studies on the probability of events following
treatment. The benefit of carotid endarterectomy was explored using a baseline
set of parameters and a sensitivity analysis. RESULTS: The baseline scenario of a
65-year-old male patient with the model factors set at an intermediate level
showed a benefit for surgery of 3 QALMs compared with medical treatment alone.
The sensitivity analysis showed that the most favourable combination of factors
had a benefit of 13.4 QALMs and the least favourable a loss of 2 QALMs. Of all
128 factor combinations, 79.9% showed a benefit for surgery, 5.5% showed equal
benefit, and 15.6% showed a benefit for medical treatment. CONCLUSIONS: Computer
simulations have the potential for deriving estimates of benefit for different
patient groups from the results of clinical trials. Combined with reliable
information on costs, the technique could also demonstrate variations in cost
effectiveness for these groups. For patients following a transient ischaemic
attack, the results from this simulation and limited cost information suggest
that carotid endarterectomy is unlikely to be a cost-effective intervention in
the UK for many patient groups despite a reduction in the risk of stroke.
PMID- 10180393
TI - Tough times, tough decisions: body armor use in EMS.
PMID- 10180394
TI - Prehospital triage.
PMID- 10180395
TI - EMS incident management: the treatment sector in mass casualty events. A multi
part series.
PMID- 10180396
TI - A view from the inside. Part one: Becoming an EMT.
AB - The number of recreational divers is increasing rapidly. While many programs
exist to make the sport safer, the potential for EMS to deal with cases of DCS
and AGE increases. There is a clear need for EMS providers in all areas,
regardless of proximity to water, to be aware of signs, symptoms and treatment of
diving-related injuries and decompression illness. The important thing is
acquiring a basic ability to recognize DCS and AGE and provide treatment to
injured divers. Initial recognition and proper treatment of an injured diver can
save a life.
PMID- 10180397
TI - Welcome to a brave new world of no more needles.
PMID- 10180398
TI - Code Blue: how a hot medical stock blew up.
PMID- 10180399
TI - Improving the quality of private sector delivery of public health services:
challenges and strategies.
AB - Despite significant successes in controlling a number of communicable diseases in
low and middle income countries, important challenges remain, one being that a
large proportion of patients with conditions of public health significance, such
as tuberculosis, malaria, or sexually transmitted diseases, seek care in the
largely unregulated 'for profit' private sector. Private providers (PPs) often
offer services which are perceived by users to be more attractive. However, the
available evidence suggests that serious deficiencies in technical quality are
often present. Evaluations of interventions to promote evidence-based care in
high income countries have shown that multi-faceted strategies which increase
provider knowledge have had some success in improving service quality. A wider
range of factors needs to be considered in low and middle income countries
(LMICs), especially factors which contribute to discrepancies between provider
knowledge and practice. Studies have shown that PPs, especially, perceive or
experience patient and community pressures to provide inappropriate treatments.
LMIC governments also lack the capacity to enforce regulatory controls. Context
specific multi-faceted strategies are needed, including the local adaptation and
dissemination to providers of relevant evidence, the education of patients and
communities to adopt effective treatment-seeking and treatment-taking behaviour,
and feasible mechanisms for ensuring and monitoring service quality, which may
include a role for self-regulation by provider organizations or provider
accreditation. Developing, implementing and evaluating strategies to improve the
quality of service provision will depend on the involvement of the key
stakeholders, including policy makers and PPs. Focusing on studies from Asia,
Africa and Latin America, this paper develops a model for identifying the
influences on PPs, mainly private medical practitioners, in their management of
conditions of public health significance. Based on this, multi-faceted strategies
for improving the quality of treatment provision are suggested. Interventions
need to be inexpensive, practical, efficient, effective and sustainable over the
medium to long term. Achieving this is a significant challenge.
PMID- 10180400
TI - Why include men? Establishing sexual health clinics for men in rural Bangladesh.
AB - Subsequent to recommendations from the 1994 United Nations International
Conference on Population and Development, and given recent findings outlining the
links between control of sexually transmitted infections (STIs) and a reduction
in HIV incidence, many countries are now seeking to establish STI control
programmes. In many cases this is through a policy of providing comprehensive
reproductive health care through the maternal and child health/family planning
(MCH-FP) system. This involves management of all reproductive tract infections
including STIs. This paper demonstrates how such an approach may miss one of the
largest target groups--men. In general, men are at higher risk of initially
contracting STIs, but, once infected, their clinical management is usually
simpler than treating equivalent infections in women. It is argued that these two
factors alone make the inclusion of men in STI control programmes critical. The
paper outlines the experiences of one programme in rural Bangladesh in
establishing sexual health clinics for men within the existing service structure.
In response to client demand, the clinics moved beyond simple STI care towards
provision of comprehensive sexual health services. Finally, the paper argues that
whilst including men in sexual health programmes should never be at the expense
of providing services for women, excluding them from service provision may make
the objectives of STI control programmes unattainable.
PMID- 10180401
TI - The quality of immunization data from routine primary health care reports: a case
from Nepal.
AB - Reported high immunization coverage achieved in Nepal over the last ten years is
expected to reduce child mortality in the country. The present study, carried out
in hill district in mid-west Nepal, aimed to assess the quality of immunization
data in Nepal. The number of children who received different vaccines during one
year was obtained from three sources: 1) the Immunization REgister of three
Primary Health Care Service Outlets (PHCSOs) where each immunized child is
recorded; 2) monthly PHC Reports, which are based on the Immunization Register;
3) monthly DHO Reports, which are based on the above PHC Reports (the DHO reports
are the source of official statistics). The number of children in the PHC Reports
was higher than the number in the Immunization REgisters for all vaccines. The
number of immunizations in the DHO Reports was higher than the number in the PHC
Reports for BCG, DPT, and measles; the number was lower for poliomyelitis. The
overall number of immunizations was higher in the DHO Reports than in the
Immunization Registers, by 31% for BCG, 44% for DPT, 155% for polio, and 71% for
measles. We conclude that the official report overestimates the immunization
coverage in the district. The immunization programme, therefore, might not result
in the expected reduction of morbidity and mortality despite the investment in
the programme and reported high coverage.
PMID- 10180402
TI - The census-based, impact-oriented approach: its effectiveness in promoting child
health in Bolivia.
AB - This paper describes the effectiveness for child health of a primary health care
approach developed in Bolivia by Andean Rural Health Care and its colleagues, the
census-based, impact-oriented (CBIO) approach. Here, we describe selected
achievements, including child survival service coverage, mortality impact, and
the level of resources required to attain these results. As a result of first
identifying the entire programme population through visits at least biannually to
all homes and then targeting selected high-impact services to those at highest
risk of death, the mortality levels of children under five years of age in the
established programme areas was one-third to one-half of mortality levels in
comparison areas. Card-documented coverage for the complete series of all the
standard six childhood immunizations among children 12-23 months of age was 78%,
and card-documented coverage for three nutritional monitorings during the
previous 12 months among the same group of children was 80%. Coverage rates in
comparison areas for similar services was less than 21%. The local annual
recurring cost of this approach was US $8.57 for each person (of all ages) in the
programme population. This cost includes the provision of primary care services
for all age groups as well as targeted child survival services. This cost is well
within the affordable range for many, if not most, developing countries. Manpower
costs for field staff in Bolivia are relatively high, so in countries with lower
salary scales, the overall recurring cost could be substantially less. An Expert
Review Panel reviewed the CBIO approach and found it to be worthy of replication,
particularly if stronger community involvement and greater reliance on volunteer
or minimally paid staff could be attained. The results of this approach are
sufficiently promising to merit implementation and evaluation in other sites,
including sites beyond Bolivia.
PMID- 10180403
TI - Factors affecting home delivery in the Kathmandu Valley, Nepal.
AB - This nested case-control study compares the characteristics of mothers having
home or institutional deliveries in Kathmandu, Nepal, and explores the reasons
given by mothers for a home delivery. The delivery patterns of mothers were
identified in a cross-sectional survey of two communities: an urban area of
central Kathmandu (Kalimati) and a peri-urban area (Kirtipur and Panga) five
kilometres from the city centre. 357 pregnant women were identified from a survey
of 6130 households: 183 from 3663 households in Kirtipur and Panga, 174 from 2467
households in Kalimati. Methods involved a structured baseline household
questionnaire and detailed follow-up of identified pregnant women with structured
and semi-structured interviews in hospital and the community. The main outcome
measures were social and economic household details of pregnant women; pregnancy
and obstetric details; place of delivery; delivery attendant; and reasons given
for home delivery. The delivery place of 334/357 (94%) of the pregnant women
identified at the survey was determined. 272 (81%) had an institutional delivery
and 62 (19%) delivered at home. In univariate analysis comparing home and
institutional deliverers, maternal education, parity, and poverty indicators
(income, size of house, ownership of house) were associated with place of
delivery. After multivariate analysis, low maternal educational level (no
education, OR 5.04 [95% CI 1.61-15.8], class 1-10, OR 3.36 [1.04-10.8] compared
to those with higher education) and multiparity (OR 3.1 [1.63-5.74] compared to
primiparity) were significant risk factors for a home delivery. Of home
deliverers, only 24% used a traditional birth attendant, and over half were
unplanned due to precipitate labour or lack of transport. We conclude that poor
education and multiparity rather than poverty per se increase the risk of a home
delivery in Kathmandu. Training TBAs in this setting would probably not be cost
effective. Community-based midwife-run delivery units could reduce the incidence
of unplanned home deliveries.
PMID- 10180404
TI - Performance of village pharmacies and patient compliance after implementation of
essential drug programme in rural Burkina Faso.
AB - After implementation of a nation-wide essential drug programme in Burkina Faso a
prospective study was undertaken consisting of non-participant observation in the
health centre and in the village pharmacy, and of household interviews with the
patients. The study covered all general consultations in nine health centres in
three districts over a two-week period as well as all client-vendor contacts in
the corresponding village pharmacies; comprising 313 patients in consultations
and 498 clients in eight village pharmacies with 12 vendors involved in
dispensing 908 drugs. Additionally patients were interviewed in their households.
Performance and utilization of the village pharmacy: 82.0% of the drugs
prescribed in the health centres were actually dispensed at the village pharmacy,
5.9% of the drugs were not available at the village pharmacy. Wrong drugs were
dispensed in 2.1% of cases. 41.3% of the drugs dispensed in the village pharmacy
were bought without a prescription. Differences are seen between the district and
are put in relation to different onset of the essential drug programme. Patient
compliance: Patients could recall the correct dosage for 68.3% of the drugs. Drug
taking compliance was 63.1%, derived from the pills remaining in the households.
11.5% of the drugs had obviously been taken incorrectly to such an extent that
the occurrence of undesired drug effects was likely. The study demonstrates the
success of the essential drug programme not only in performance but also in
acceptability and utilization by the population.
PMID- 10180405
TI - Ivermectin distribution using community volunteers in Kabarole district, Uganda.
AB - Ivermectin mass distribution for the control of onchocerciasis in Uganda began in
1991. This report describes a community based ivermectin distribution programme
covering two foci in the Kabarole district which have an estimated 32,000 persons
infected and another 110,000 at risk. Through nodule palpation in adult males,
143 villages were identified where nodule prevalence exceeded 20%. Skin snips
were also taken from a sample of the population to measure changes in community
microfilarial load (CMFL) with treatment. The delivery programme was integrated
into the district health management structure, and used community volunteers
supervised by medical assistants from adjacent health facilities for annual
ivermectin distribution campaigns. After initial efforts by the community to
support distributors in-kind proved inadequate, ivermectin distributors earned
money retailing condoms as part of the social marketing component of district
STD/AIDS programme. Reduction in the CMFL ranged from 40-62% twelve months after
the second ivermectin treatment in three villages, and from 69-84% six months
after the fourth round of treatment in two villages. After four years of
treatment, 85% of eligible persons were receiving ivermectin from community
volunteers in each treatment cycle. Drop out rates among volunteers did not
exceed 20% over the four years reported here. The direct cost of treatment was US
$0.29 per person. Among the reasons for low per-person treatment costs were the
strong supervisory structure, the presence of health centres in the foci and a
well developed and capable district Primary Health Care management team.
PMID- 10180406
TI - Satisfaction with outpatient health care services in Manica Province, Mozambique.
AB - The objective of the study was to describe ambulatory health care services,
determine the level of client satisfaction, and identify obstacles to care in a
rural area of Mozambique. Exit surveys at 34 health clinics in Manica Province
were completed on a sample of 879 adults representing between 1% and 2% of the
average monthly visit totals at each clinic. Eighty-three per cent of
interviewees were women. Just over half of the visits were for paediatric
patients. Men were more likely to be at the clinic for their own health care
needs than women (81% vs. 40%, p < 0.001). Of patients seen for acute illness,
45% were examined, 22% received preventive education, and 23% received prognostic
information. Overall, 55% of interviewees believed that the service they received
was good or very good, 32% rated it as fair, and 13% as poor. Satisfaction was
positively associated with increased training level of the provider (p < 0.005),
and shorter waiting times (p < 0.001). The most common complaints about the
clinic visits were lack of adequate transportation, long waiting times, lack of
physical examinations, and failure to receive prescribed medications. These
findings suggest that the majority of Mozambicans interviewed are moderately
satisfied with the available outpatient services in Manica. Provider training,
provider availability and distribution of medicines were areas identified by
respondents as needing improvement.
PMID- 10180407
TI - Cost recovery in Ghana: are there any changes in health care seeking behaviour?
AB - The study aimed to investigate the impact on health care seeking behaviour of the
cost-sharing policies introduced in Ghana between 1985 and 1992. Qualitative
research techniques were used to investigate the behaviour of patients after the
introduction of these policies. Focus group discussions of cohorts of the
population and in-depth interviews of health workers and selected opinion leaders
were used to collect data from rural and urban health care facilities in three
districts of Ghana. The study findings indicate that the cost recovery policies
have led to an increase in self-medication and other behaviours aimed at cost
saving. At the same time, there is a perception of an improvement in the drug
supply situation and general health delivery in government facilities. The study
advocated enhanced training of drug peddlers and attendants at drug stores,
especially in rural areas. User fee exemption criteria need to be worked out
properly and implemented so that the very needy are not precluded from seeking
health care at hospitals and clinics.
PMID- 10180408
TI - How to do (or not to do) ... a logical framework.
PMID- 10180409
TI - Pediatric Ambulatory Clinic, Children's Medical Center of Northwest Ohio.
Karlsberger Healthcare Group.
PMID- 10180410
TI - Guide to hip replacements. Keeping the ball rolling.
PMID- 10180411
TI - Fighting cancer into the next century.
PMID- 10180412
TI - HIV/AIDS. Triple jump.
PMID- 10180413
TI - Cystic fibrosis. Greater expectations.
PMID- 10180414
TI - Primary care groups. The cultivated commissioner.
AB - The government's proposals for primary care groups assume GPs will be able to
direct commissioning organisations more successfully than their fundholder
predecessors. Under the previous system, practices incapable of managing a budget
and purchasing health services were, in effect, ruled out of fundholding.
Guidelines are needed specifying the skills and expertise required for membership
of PCGs.
PMID- 10180415
TI - Primary care. Life after LIZ (London Initiative Zone).
AB - A survey of primary care initiatives in casualty departments in North Thames
found confusion over aims and managerial accountability. Nurses and GPs staffing
these projects often overrode the triage decisions made by casualty staff. The
schemes lacked the information systems required for a full analysis of costs and
benefits.
PMID- 10180416
TI - Equipment costs. Slow on the uptake.
AB - The failure of hospitals to analyse the costs and benefits of equipment is
costing the NHS millions. Hospitals should analyse the relative merits of buying
and hiring special equipment, such as beds, for reducing pressure sores. The
Department of Health should produce best buy guides for equipment.
PMID- 10180417
TI - Public consultation. Up and ATAM (aims, timing, audience, method).
AB - Although the NHS has some shining examples of public and user involvement, many
still view it as an optional extra. Policy makers need to adopt a broader
strategy for involving users, carers, staff and the wider public. Badly done
public consultation will cause problems for policy makers, alienate participants
and fuel public cynicism.
PMID- 10180418
TI - On the evidence. Pre-school hearing, speech, language and vision screening.
PMID- 10180419
TI - Chief executives. A gender for change.
PMID- 10180420
TI - Telephone services. Holding the line.
PMID- 10180421
TI - Patients' views. Clear views.
PMID- 10180422
TI - Finance managers. Shake up or ship out.
PMID- 10180423
TI - Collaboration--the big C.
PMID- 10180424
TI - Osteoporosis. Coming to the crunch.
PMID- 10180425
TI - Guide to coronary bypass. The beat goes on.
PMID- 10180426
TI - Multiple sclerosis. Blurred vision.
PMID- 10180427
TI - Paediatric surgery. More than meets the eye.
PMID- 10180428
TI - Pay. Fair shares of the kitty?
PMID- 10180429
TI - South Africa. Tone of contention.
PMID- 10180430
TI - On the evidence. Lung cancer.
PMID- 10180431
TI - Treatment refusals by pregnant women.
PMID- 10180432
TI - Medical privacy? Forget it!
PMID- 10180433
TI - The only sane way to deal with pre-certification.
PMID- 10180434
TI - Net worth has climbed to new heights. Results from our new financial survey.
PMID- 10180435
TI - Remember when ... a woman doctor was a rarity?
PMID- 10180436
TI - Quality care. Do the bull and the bear affect health care?
PMID- 10180437
TI - When it's time to look for a new job.
PMID- 10180438
TI - Can it be--more health-care bureaucracy?
PMID- 10180439
TI - Assisted suicide is legal. Now what?
PMID- 10180440
TI - How to figure the cost of every little (and big) thing you do.
PMID- 10180441
TI - Doctors and divorce. Don't let your practice kill your marriage.
PMID- 10180442
TI - Answering your questions on awards for outstanding laboratorians.
PMID- 10180443
TI - Conquering performance improvement documentation for JCAHO.
PMID- 10180444
TI - MLO's national CLIA '88 survey, Part 2: Praise versus protest--views from both
sides of the fence.
AB - While a recent survey shows that more laboratorians approve of CLIA now than in
the past, a considerable enclave remain opposed to this law. Among the key issues
that continue to dishearten and incite the clinical lab: the proposed exemption
of POLs and diminished personnel standards.
PMID- 10180445
TI - As others see us, Part 1. Back to basics. Career challenges for the laboratorian.
AB - It's time for the laboratorian to emerge from the lab and become an integral part
of the healthcare team. We must make others aware of our skills in critical
thinking, decision making, quality assurance, and total quality management.
PMID- 10180446
TI - Automation, Part 2. Modular stepwise automation and the future of diagnostic
testing.
PMID- 10180447
TI - AHA settles suit over '96 convention.
PMID- 10180448
TI - Fraud compromise offered. AHA urges guidelines on False Claims Act enforcement.
PMID- 10180449
TI - Mass. ruling hits insurance plan.
PMID- 10180450
TI - Protecting rural providers. New law in Georgia targets discrimination by
insurers.
PMID- 10180451
TI - Acting like insurer pays off for Pa. HMO.
PMID- 10180452
TI - Chipping away at balanced-budget law.
AB - While no piece of legislation in Washington is every really finished, the
lobbying over last year's balanced-budget law is especially fierce. Special
interest groups of every stripe--especially healthcare groups--are working
furiously behind the scenes to change what they don't like about the law and keep
the parts that benefit their interests.
PMID- 10180453
TI - VHA delivers messaging. Network lets physicians and hospitals share clinical
data.
PMID- 10180454
TI - Fewer uninsured. More highly rated systems opting for bond insurance.
PMID- 10180455
TI - Setback for providers. Judge dismisses lawsuit challenging PATH probe.
PMID- 10180456
TI - Medicare trust fund gets healthier.
PMID- 10180457
TI - Pro-insurance policy? AHA board's HMO connections may influence agenda.
PMID- 10180458
TI - Courting disaster. Physician recruiting practices create legal problems.
PMID- 10180459
TI - Conditional approval. Mass. activists win changes in hospitals' consolidation.
PMID- 10180460
TI - A rivalry gets ugly. Florida hospital's antitrust suit bypasses state, federal
regulators.
PMID- 10180461
TI - The heart of the matter. Calif. outcomes report improves, but flaws remain.
PMID- 10180462
TI - Let's at least look good. GOP seen as proposing managed-care paper tiger.
PMID- 10180464
TI - Rockford Physicians Council, USA.
PMID- 10180463
TI - AMA supports collective voice, but not pickets.
PMID- 10180465
TI - Making the pieces fit. After assembling their care networks, systems' next big
challenge is to build a unifying information infrastructure.
AB - Five years into a manic pace of consolidation, hospital-based health delivery
systems across the country are feeling the pressure to establish computer
networks to unite all sites and services. In the campaign to lift healthcare out
of an era of paper and pencil, organizations have spent freely on healthcare
software applications. But computer pros say that's not enough.
PMID- 10180467
TI - Per diem rate set for skilled nursing.
PMID- 10180466
TI - A different California. In San Joaquin Valley, healthcare presents challenges.
PMID- 10180468
TI - An unwanted enemy. Hospitals try to convert radiologists to their interests.
PMID- 10180469
TI - Plugging the holes. CFOs work to offset cutbacks under balanced-budget law.
PMID- 10180470
TI - New fund targets healthcare start-ups.
PMID- 10180471
TI - Buying for the long-term. Payoff of Columbia hospital deal depends on strategy.
PMID- 10180472
TI - Managed-care Godzilla. United-Humana deal puts pressure on providers, insurers.
PMID- 10180473
TI - Preparing for the worst. Group gets ready to swat year-2000 computer bugs.
PMID- 10180474
TI - Medicare cuts between rock and hard place.
PMID- 10180475
TI - Reform bill deja vu. House GOP pushing managed competition proposal.
PMID- 10180476
TI - Doc unions don't solve problems.
PMID- 10180477
TI - Veterans, children first. Consolidation of federal healthcare services leads some
VA clinics to expand patient mix.
AB - Facing flat federal appropriations, the Department of Veterans Affairs is
fattening its budget through service contracts with other agencies. That's meant
young children and World War II veterans mix in some of its clinics. Although
conceding that new funds are needed, veterans groups fear the VA's traditional
customers will be shortchanged in the transition.
PMID- 10180479
TI - Bug-hunters join forces. Groups compile and compare millennium-related data.
PMID- 10180478
TI - Information integration. Health networks getting wired, but too slowly, some say.
PMID- 10180480
TI - Staying private. Penny Pritzker keeps assisted-living business in the family.
PMID- 10180481
TI - A house of disarray. Report: AMA board negligent of fiduciary duties.
PMID- 10180482
TI - Revolutionizing billing and care management with managed care data warehouses.
PMID- 10180483
TI - Risk alignment in health care quality and financing: optimizing value.
AB - How should health care best consolidate rational cost control while preserving
and enhancing quality? That is, how can a system best optimize value? A
limitation of many current health management modalities may be that the power to
control health spending has been expropriated from physician providers, while
they are still fully responsible for quality. Assigning responsibility without
authority is a significant predicament. There are growing indications that well
organized, well-managed groups of high quality physicians may be able to directly
manage both types of risk-quality and financial. The best way to optimize
responsibility and authority, and to control financial and quality risks, is to
place such responsibility and authority within the same entity.
PMID- 10180484
TI - Value-based health care. Part I: Physicians reestablishing clinical autonomy.
AB - Clinical decision-making was once the sole purview of physicians, but no longer.
Medical judgment has been usurped by third parties in the name of cost control.
To reestablish this rightful authority, physicians must organize to assume the
financial risks for their patients' health, using objective, clinical information
to deliver superior quality outcomes. To successfully manage their patients'
clinical and financial risks, physicians need to: (1) establish a structure
independent of the hospital medical staff for outpatient contracting; (2) secure
a capital partner that supports their independent, clinical decision-making; and
(3) be leaders in acquiring and effectively using clinical information that
accurately risk-adjusts and integrates both inpatient and outpatient data for all
episodes of care. Physicians who acquire these skills will secure premium
contracts from purchasers who are demanding value-based health care delivery.
PMID- 10180485
TI - Purchasers and the impact of managed care on physicians.
AB - In much the same way that demands by managed care organizations are shaping the
way physicians practice, health care purchasers impact how managed care
organizations operate. Corporations purchase managed health care through their
employee benefits programs, and understanding the language, objectives, and
limitations of these purchasers is essential to grasping the forces influencing
managed care organizations and the modern practice of medicine. The emergence of
value-based purchasing as a strategic corporate approach to health benefits
programs will dictate the forces on physicians, hospitals, and managed care
organizations for years to come. These forces have already led to price
reductions, health plan accreditation, employee-directed report cards, outcomes
management, and organized systems of care, and they will determine the broad
outlines of the emerging U.S. health care system.
PMID- 10180486
TI - Generalists or specialists--who does it better?
AB - Managed care companies encourage primary care physicians to limit referrals to
specialists and provide as much of the needed services themselves. As a result,
generalist and specialist physicians are now in direct competition with one
another. Is the care provided by generalist and specialist physicians different
in terms of quality and cost? The authors reviewed the literature over the past
five years and found 21 articles comparing the care between specialists and
generalists. They realized asking who does it better, the generalists or the
specialists, is the wrong question to explore. Physicians must come together to
design systems of care that maximize the long-term health of patients and deliver
care in a coordinated and efficient manner. The emphasis should be on creating
value for the consumer across the continuum of providers and through time.
Competition between generalists and specialists in a fragmented system only
serves to further weaken the position of physicians in the health care industry.
PMID- 10180487
TI - Physician report cards: now and in the future.
AB - The six methods used to create physician performance reports-a less pejorative
term than physician report cards-are seriously flawed. These current approaches
are peer review, essay-style reports, raw data, statistical reports, outcome
analysis, and aggregate variation from guidelines. We must deliver what we
promise in information designed to confirm dependable practitioner performance.
Otherwise, we risk confirming, instead, the public's suspicion that the emphasis
in "managed care" is too much on managing profit and too little on patient care.
This article explores a plan for how to proceed with evaluating physician
performance.
PMID- 10180488
TI - Finding a new path.
AB - When a clinician becomes a physician-executive, the shift is abrupt, confusing,
and marked by few signposts. To be an organizational leader-especially in the
1990s, in health care more than in any other industry-is to be a master of
teamwork, a maven of process, at home with ambiguity, comfortable with change, a
nurturer of consensus, yet decisive, ready to move in the face of all the
ambiguity. The hyphenated physician-executive lives in a state of culture shock.
The first major step to overcoming this unfamiliar terrain is to recognize that
the traits of the true organizational leader are, in fact, skills. The second
step is to learn these skills, to set out deliberately, this far along in life,
on a new kind of training, a new path.
PMID- 10180489
TI - The new rules of leadership and organizational politics.
AB - As the health care industry continues to experience unprecedented change,
organizational politics are also evolving. Major changes are underway in the
rules of engagement and how management and workers behave on the job. The new
rules of the game include: Practice leadership, not management; practice
inclusion with a vengeance; practice modesty and consideration and demand both;
act on rumor, don't await confirmation; aggressively collect allies; understand
the politics of voice mail; and know that position power isn't personal power.
PMID- 10180490
TI - The art of delegation.
AB - Effective delegation is a large of a manager's position. Physician executives are
expected to be skilled delegators and able to lead team efforts to meet larger
organizational goals. Delegation should be a five-step process: (1) Describe the
results you want; (2) Listen for suggestions about how the task should be done;
(3) Give autonomy and freedom to accomplish the task; (4) Follow up; and (5) Give
feedback and credit. This column explores the art of delegating and how to assess
your skills in this key management area.
PMID- 10180491
TI - Health care applications of complexity science. Life at the edge of chaos.
AB - The authors explore complexity science, a relatively new field of inquiry, which
holds for both clinicians and health care leaders the real possibility of
stimulating fresh insights and approaches to health and medical care-both its
provision and its organization. Two case studies are presented to illustrate how
complexity theory can provide health care leaders with a new perspective on how
to address the myriad challenges they confront daily: (1) a patient with
dissociative identity disorder; and (2) a physician task group charged to advise
on hospital medical staff reorganization and governance. These case studies help
clinicians and leaders of health care organizations understand how complexity:
(1) may be relevant, even helpful, as they consider difficult challenges in both
patient and organizational management; and (2) might emerge as a synthesizing
force as they face the extraordinarily complicated task of jointly creating
integrated health care systems. A resource section is provided for those who may
wish to further pursue the topic.
PMID- 10180492
TI - Boldly going where no one has gone before.
AB - With all the changes occurring in the U.S. health care system come new
opportunities for physician executives willing to boldly go where no one has gone
before. These positions are being newly created and thus are somewhat undefined
and uncharted. Health care organizations want individuals for high-risk positions
with unique skill sets and bright, new ideas. Organizations want to find people
who can do what has never been done before-for them, at least, if not anywhere in
the universe. How does that translate into experiences that you might want to
acquire? Most organizations today are looking for individuals with some
networking experience, but analogous experience (such as in a multi-site medical
group or active involvement in formation of IPAs) is often a good alternative. In
addition, true line experience in one or more organizations is a solid
credential. Knowledge of where managed health care dollars begin and end is a
necessity. As always, executive style and presence are expected.
PMID- 10180493
TI - Focus on a necessary benefit.
AB - More than 9,000 home health agencies provide services to Medicare beneficiaries.
In 1996, 10 percent of Medicare beneficiaries received home health services at a
total cost of +18 billion. Rapid growth has forced changes in the structure of
the benefit payment system and has made home health an attractive area for
fraudulent activities which are now being targeted. Collectively, this important
benefit and relatively new industry will face changes in the way they do business
and deliver services.
PMID- 10180494
TI - Mergers: enhancing human resources management.
AB - The health care industry is experiencing merger mania, but the majority of its
current leadership underestimates the importance that significant differences in
corporate culture and employee morale play among physicians and others in
implementing such organizational objectives as enhancing access, reducing cost,
and improving quality of care. The key human resources management issues are
discussed that are too often overlooked and frequently sidetracked in the
formation of powerful health networks now so prevalent in almost every
metropolitan region. The authors conclude that in America's intensely competitive
managed care environment, there are a number of critical human resources
management ingredients that deal makers need to achieve from these mergers in
order to ensure their perceived objectives: (1) paying far greater attention to
variations in corporate culture and employee morale; (2) reducing total salary
and fringe benefit costs; and, (3) concurrently recruiting and maintaining a
qualified and stable workforce that focuses more decisively on clinical-fiscal
concerns so as to improve quality of patient care at a lower cost.
PMID- 10180495
TI - Physician/hospital business relationships. Sorting through the options.
AB - Providers recognize the critical role of physician/hospital partnerships in the
newly emerging health care delivery system. However, the possibilities available
for establishing such partnerships can be overwhelming. The authors provide a
critical review of the options for physician/hospital business relationships.
They emphasize the need to match physician/hospital strategies to local market
characteristics, develop market-based business objectives, and structure
physician/hospital relationships to support the achievement of business
objectives.
PMID- 10180496
TI - When is a physician network a group?
AB - Developing a network of physicians into a high-performing group requires a
cultural transformation. The hallmarks, as well as the obstacles, to achieving
this are reviewed by two experienced consultants. The requirements of highly
successful physician organizations range from sharing a common mission, vision,
and values to developing an effective infrastructure to having visionary
leadership. Barriers to successful physician groups include a lack of clarity of
purpose and goals, lack of quality standards, and an absence of shared learning.
A blueprint on how to become a successful physician group is provided.
PMID- 10180497
TI - Integrated delivery systems. Evolving oligopolies.
AB - The proliferation of Integrated Delivery Systems (IDSs) in regional health care
markets has resulted in the movement of these markets from a monopolistic
competitive model of behavior to an oligopoly. An oligopoly is synonymous with
competition among the few, as a small number of firms supply a dominant share of
an industry's total output. The basic characteristics of a market with
competition among the few are: (1) A mutual interdependence among the actions and
behaviors of competing firms; (2) competition tends to rely on the
differentiation of products; (3) significant barriers to entering the market
exist; (4) the demand curve for services may be kinked; and (5) firms can benefit
from economies of scale. An understanding of these characteristics is essential
to the survival of IDSs as regional managed care markets mature.
PMID- 10180498
TI - The emerging medical/industrial complex. The industrialization of medicine.
AB - Until recently, the traditional practice of medicine has been thought of as a
cottage industry practiced by individuals or small partnership groups. The
transition of practice settings to large groups, multi-specialty groups, and
corporations has paved the way to industrialization, with even larger health care
organizations primarily managed by non-physicians. The similarities of these
events to the industrial revolution and its impact on crafts guilds are striking.
In order to understand this point of view, this article explores the function and
influence of crafts guilds during stages of industrial development and the
dynamics of the changes of employment needs and employability in an industrial
environment as a comparison to what is happening in the health care field.
PMID- 10180499
TI - Israel--a health system in transition.
AB - Israeli health reform, implemented after many failed attempts throughout the
years, represents an attempt to solve problems of politicization,
dissatisfaction, unclear roles of government and public organizations, and lack
of financial accountability, while maintaining a high quality and universally
accessible health system. Despite many favorable aspects, including high quality
medical care, near universal insurance coverage, and high availability of
services, the health system has attracted criticism since its earliest days.
Israel's experience with health reform, based on a version of managed
competition, is of interest to other countries considering similar policy
decisions.
PMID- 10180500
TI - Why it matters.
AB - Physicians everywhere are facing changes in the ways they are paid, and in their
relationships with their patients. In the United States, an increasing number of
physicians are being confronted with the choice to join their practice to a
physician service organization (PSO) or some other capitated financial structure
in which they collectively put themselves at financial risk for the health of
their patients. In all these decisions, the biggest handicap is fear. Some
physicians let fear keep them from changing. Others let fear drive them too
quickly into change that turns out to be unwise. The fear of change-the fear of
the unknown, of things that, deep down, under the professional veneer, we wonder
whether we can handle-is quite real. It is immediate and nearly constant. How can
you drive out the fear? There is no simple answer. The complex answer starts with
daily practice, with taking the practice deeper, taking it wall-to-wall. Here are
some ideas for dealing with the fear of change, from owning up to your true
feelings, to acknowledging failure, to breaking the change down into its smallest
components.
PMID- 10180501
TI - Your direct reports loathe you. Does it matter?
AB - Chalk it up to the labor shortage or to growing worker independence, but today
almost everyone agrees that management effectiveness rests heavily on grass roots
support. Why do subordinates despise a superior? Indecisiveness, non-support,
expense account abuse, and arrogance are some of the documented reasons. Your
direct reports can cause you to fail and their perfidy will never be detected.
They can question your competence and decisions often-through the grapevine
bombarding top management with derogatory information it ultimately can't or
won't ignore. Moreover, the movement of workers from organization to organization
means that negative gossip will be repeated in dozens of grapevines. What is the
worst thing disgruntled workers do to a manager's career? Not only will victims
protest and flack your sins in the grapevine, they'll vote with their feet.
Worker shortages mean that turnover is watched as closely as salary expenses.
Explored herein are some signs that should cause a manager to examine how he or
she stands with the troops.
PMID- 10180502
TI - Why become a certified physician executive?
AB - What is the CPE Tutorial and how can it help advance the careers of physician
executives? This five-day program teaches executive skills that make physician
executives more valued in the marketplace. When candidates successfully pass an
evaluation judged by a panel of health care CEOs, recruiters, and Fellows of the
College, they become Certified Physician Executives (CPEs). This certification
provides recognition to potential employers that CPEs have: stature as a
physician; been successfully tested in all disciplines of medical management;
demonstrated management experience; and successfully completed the Tutorial with
a five minute presentation describing skills and competencies on the last day. As
CPEs become widely known in the marketplace, the designation will be a valued
credential that helps physician executives get and keep desirable positions, as
well as advance to the next level in their careers.
PMID- 10180503
TI - Global view offers good news for physician executives.
AB - Do all physician executives have much "catching up" to do in relation to their
non-MD colleagues? A comparison of the role of the physician executive versus the
non-MD executive/administrator provides a big picture view and signals new
opportunities for physicians in the evolving health care system. Physician
executives have only recently become invested in the health care executive suite
and are less wedded to old methods and "classic" ideas. They are more likely to
be able to adapt to new circumstances, jettisoning traditional approaches that
have outlived their usefulness. But each group-physician executives and their MHA
or MBA-credentialed, non-MD colleagues- has much to offer to or learn from the
other. By retaining those skills that are applicable, while also adapting the
useful characteristics of the "traditional" health care administrator, a
physician executive can increase the likelihood of success today.
PMID- 10180504
TI - The quality debate: Consumer Bill of Rights.
AB - Inherent in any discussion on quality for a delivered service is understanding
what outcomes you want to achieve and assuring that your consumer agrees. The
Presidential Commission's Consumer Bill of Rights supports this principle. Its'
goals include: strengthening consumer confidence by providing them with a system
responsive to their needs and with a credible mechanism to address their
concerns; reaffirming the importance of a strong relationship between patients
and their health care providers; and, reaffirming the role consumers play in
safeguarding their own health. Striking the balance between cost and quality
requires all the stakeholders of the health care system to focus on the true
issues that impact quality: outcomes, accountability, and consumer satisfaction,
however defined.
PMID- 10180506
TI - Glaucoma.
PMID- 10180505
TI - Merger mania: physicians beware.
AB - Corporate consolidations, mergers, and acquisitions would seem to provide immense
promise in furthering the development of health networking because they affect
the governance of entire organizations, rather than simply establishing revised
arrangements for specific services or patients. Yet, a limited number of
empirical studies have been published to date that explore whether hospital
mergers actually improve access, reduce cost, or improve quality of care; and,
among the reports available, the conclusions are somewhat equivocal. Physicians
should be cautious of these mergers, since they seem to focus either on
eliminating a direct competitor or on forming a large horizontally and vertically
diversified health network that then can become a major player in gaining
exclusivity in managed care contracting. With either of these merger strategies,
there are antitrust-type concerns that competition among physicians and other
providers will be significantly curtailed, and that consumers will end up with
fewer choices in obtaining cost effective, quality patient care.
PMID- 10180507
TI - The TIGR gene, pathogenic mechanisms, and other recent advances in glaucoma
genetics.
AB - Important advances have been made within the past year in the area of glaucoma
genetics, including the identification of the TIGR gene for adult as well as
juvenile GLC1A glaucoma, a P450 gene for GLC3A congenital glaucoma, and a
bicoidhomeobox transcription factor gene RIEG for developmental glaucoma. The
cloning of TIGR as a candidate gene for glaucoma is based on its distinctive
induction in human trabecular meshwork cells and tissues, its induction profile,
and the expressed molecule's putative biologic properties. Results from several
laboratories showing defects in the olfactomedin homology domain of the TIGR gene
have generated particular interest concerning potential pathogenic mechanisms.
Recent progress in glaucoma genetics has also included the identification of new
loci in familial adult open-angle glaucoma, the identification of a locus
associated with pigment dispersion syndrome, and the collection of new families
for linkage analyses and clinical assessments. Taken together, these findings
offer future prospects for improving diagnostic criteria, for understanding
disease etiologies, and for developing improved therapeutic strategies.
PMID- 10180508
TI - Classification of filtering blebs in trabeculectomy: biomicroscopy and
functionality.
AB - The long-term success of filtering surgery is not dependent on surgical technique
alone. The development of the filtering bleb in the postoperative period, in
particular with regard to wound healing and subconjunctival scarring, is equally
important. Morphologic changes of the developing filtering bleb after
trabeculectomy can predict early failure even if the intraocular pressure is
still normal. A basic understanding of wound healing processes and histologic
changes of the developing filtering bleb are mandatory to interpret correctly the
morphologic appearance of the developing filtering bleb. In clinical practice,
follow-up of the filtering bleb according to a standardized morphologic
classification may help to predict outcome and provide clues for the necessity
and timing of further treatment.
PMID- 10180509
TI - The vascular pattern of the optic nerve and its potential relevance in glaucoma.
AB - Evidence that vascular factors contribute to the pathogenesis and development of
glaucomatous optic neuropathy continues to accumulate. A higher than expected
prevalence of systemic vascular disorders in individuals with glaucoma has been
documented. New sophisticated in vivo analysis techniques, such as ultrasound
color Doppler imaging, suggest that decreased blood flow velocity and increased
vascular resistance are present in the vessels serving the optic nerve of human
subjects with glaucoma, implying the presence of either organic or functional
vascular disorders in these individuals. Recognizing that different analysis
techniques have led to conflicting observations, experimental models have been
developed to provide an additional tool with which to interpret the effects of
compromised optic nerve perfusion.
PMID- 10180510
TI - Selectivity of site of action and systemic effects of topical alpha agonists.
AB - Clonidine hydrochloride, apraclonidine hydrochloride, and brimonidine tartrate
constitute the three topical alpha agonists that are used in the treatment of
elevated intraocular pressure. All the alpha agonists have prejunctional (alpha
2) as well as postjunctional (alpha 1) effects. Within the past year, questions
have arisen about their local and systemic effects, and their effects upon the
optic nerve. We will, therefore, attempt to clarify these points, to provide a
greater understanding of the role of alpha agonists in glaucoma therapy.
PMID- 10180511
TI - Pathogenetic mechanisms of glaucoma not related to intraocular pressure.
AB - The pathogenesis of the diseases termed open-angle glaucoma remains elusive but
progress is being made in understanding more clearly the optic nerve head,
vascular, and cellular mechanisms that are associated with them. Even though the
greatest risk factors remain intraocular pressure, age, race and refractive
error, the association with vascular disease continues to unfold in the
literature. Clinical and laboratory studies, although not addressing mechanisms
directly as far as we know, continue to probe potential pathways that will
ultimately lead to subsets of open-angle glaucoma. Only when this is accomplished
will we be able to focus therapy at pathogenesis rather than at risks.
PMID- 10180512
TI - Role of ultrasound biomicroscopy in the differentiation of block glaucomas.
AB - Ultrasound biomicroscopy has allowed us to elucidate the anatomic variations and
underlying mechanisms in angle-closure glaucoma. Four levels of anatomic block
can be distinguished, and a specific approach to treatment exists for each level
to correct the abnormal forces leading to closure of the angle. As more
quantitative approaches are developed, our understanding of these disorders will
become increasingly sophisticated.
PMID- 10180513
TI - Direct involvement of trabecular meshwork in the regulation of aqueous humor
outflow.
AB - Our new hypothesis for the regulation of aqueous humor outflow suggests that the
trabecular meshwork is not a passive filter but an active contractile element
contributing to the ciliary muscle traction affecting it. The trabecular meshwork
contains contractile smooth-muscle-specific alpha-actin filaments, and its cells
exhibit electrical properties typical for smooth muscle cells. Contractility
measurements performed for the first time in isolated trabecular meshwork enable
a functional comparison with ciliary muscle. Pharmacologic outflow regulation has
been determined in isolated perfused anterior segments with intact trabecular
meshwork and total absence of ciliary muscle. Substances that contracted isolated
trabecular meshwork (e.g., pilocarpine) decreased the outflow rate, whereas
relaxants (e.g., low-dose epinephrine) increased it. The concept of a functional
antagonism between the trabecular meshwork and the ciliary muscle has to be
considered.
PMID- 10180514
TI - Abnormalities of microcirculation in glaucoma: facts and hints.
AB - Many risk factors associated with glaucoma have been identified recently. The
best known of these is increased intraocular pressure (IOP). Among the others,
however, vascular risk factors play a major role. Although such vascular factors
were already postulated more than 100 years ago, only recent technical
developments have afforded systematic investigations of associated
microcirculatory disturbances and basic principles of blood flow regulation. In
glaucoma, besides IOP, vascular dysregulation (such as local vasospasm and
systemic hypotension, resulting in impaired autoregulation of blood flow in the
optic nerve head, the choroid, and other ocular tissues) seems to be a major risk
factor. However, multiple coacting factors, which are not limited to the eye but
are, rather, symptoms of a systemic disease, seem to be involved in the damaging
process.
PMID- 10180515
TI - Noninvasive measurement of oxygen tension in the optic nerve head.
AB - Understanding the pathophysiology of the optic nerve head (ONH) requires precise
knowledge of the oxygenation of this tissue. Previous investigations used methods
based on oxygen sensitive microelectrodes to measure the partial pressure of
oxygen in the ONH tissue. These microelectrodes are inserted into the eye through
the pars plana. New methods are now being developed to measure the intravascular
PO2 in the ONH. They are based on the quenching of phosphorescence of a porphyrin
dye by oxygen. Although these methods require an intravenous injection of this
dye, the eye is left untouched. This article reviews these noninvasive methods.
PMID- 10180516
TI - Diagnosis and management of pigmentary glaucoma.
AB - Pigment dispersion syndrome and pigmentary glaucoma affect typically young,
myopic persons. Iridozonular contact causes pigment dispersion and obstruction of
the trabecular meshwork. Accumulation of pigment may result in transient
elevation of intraocular pressure or irreparable damage to the meshwork
accompanied by uncontrolled glaucoma. In the reviewed publications the transition
from pigment dispersion syndrome to pigmentary glaucoma was found to be 20%. The
main risk factors for the transition were ocular hypertension and myopia.
Dapiprazole, an alpha-adrenergic blocking agent, was found to be effective in
treating pigmentary glaucoma and in preventing pressure spikes after exercise.
Dapiprazole causes miosis without affecting accommodation. Yttrium aluminum
garnet laser iridotomy reduced the incidence of ocular hypertension in pigment
dispersion syndrome, although the effect was less pronounced in persons older
than 40 years of age. Lattice degeneration was found in 33.3% of the eyes with
pigment dispersion syndrome.
PMID- 10180517
TI - The psychology of the glaucoma patient.
AB - Under physiological conditions, intraocular pressure (IOP) is controlled by the
autonomic and central nervous systems. Correspondingly, nerve fibers and
neurotransmitters are present in ciliary body and trabecular meshwork. IOP
responds to physical as well as psychological stimuli in healthy individuals. In
patients with dysregulated IOP, e.g., in those with primary open-angle glaucoma,
emotional instability without a specific personality pattern could be found.
Whereas the statistical association between emotional changes and glaucoma is
obvious, the causal relationship remains to be clarified. It is at least
plausible that psychic stress may have an influence on IOP. However, the sequence
of the events is unknown (emotional disturbance can be the result of the disease
or it can be a primary sign of a nervous dysfunction). Therefore, it seems
meaningful--in addition to standard glaucoma therapy--to try to improve the
patient's emotional condition, both for treatment of the glaucoma and for the
patient's general quality of life.
PMID- 10180518
TI - Imaging of the optic disc in glaucoma: which way to go?
AB - Less than 10 years ago, fundus photography was believed to be the only method to
document optic disc changes in glaucoma. Since then, many sophisticated
electronic devices have been developed to supersede conventional photography. At
the moment, confocal laser scanning tomography, nerve fiber layer polarimetry,
and optical coherence tomography are the most popular techniques. The current
status of optic disc imaging in glaucoma can (in our very subjective opinion) be
summarized as follows. Confocal laser scanning tomography is the most
comprehensively tested electronic modality. It is perhaps the method of choice in
major glaucoma centers. Nerve fiber layer polarimetry has forged ahead during the
past 2 years and may become an alternative to confocal laser scanning tomography
in the future. Optical coherence tomography is a fascinating technique, which may
also become important in the future. Right now, however, it is still in the
experimental stage. Conventional disc photography--despite all those new
techniques--still has its place. Perhaps it is the method of choice in routine
glaucoma practice, except those clinics that can afford one of the "high tech"
machines.
PMID- 10180519
TI - Measurement of the retinal nerve fiber layer thickness in clinical routine.
AB - The possibilities and limitations of methods for indirect and direct nerve fiber
layer thickness (NFLT) measurements, and a summary of our own clinical studies
using Optic Nerve Head Analyzer (Rodenstock, Munich, Germany) (ONHA), Laser
Tomographic Scanner (Heidelberg Engineering, Heidelberg, Germany) (LTS),
Heidelberg Retinal Tomograph (Heidelberg Engineering, Heidelberg, Germany) (HRT),
Nerve Fiber Analyzer (Laser Diagnostic Technologies, San Diego, CA) (NFA) and
Optical Coherence Tomography (OCT), together with the literature of the review
period, are highlighted. A retinal hemifield test with the new parameters,
retinal asymmetry difference and retinal asymmetry index, is introduced. These
relative nerve fiber layer thickness (NFLT) measurement values are found to be
independent of age, reference plane, and disc size. This reduces the
interindividual variation of the measurements and may improve screening
possibilities for glaucoma. The detection probability for nerve fiber bundle
defects was found to be stage-dependent using HRT and NFA. For laser polarimetry,
a decreasing correlation between NFLT and visual field loss with advanced
glaucomatous disease was found. In the lower retina, a 6.9% higher NFLT was
evident compared with the upper peripapillary NFLT in healthy eyes using NFA and
OCT. This is not in correlation with perimetric retinal sensitivity, which was
found to be 3.9% higher in the lower hemifield compared with the upper hemifield.
In general, quantitative NFLT measures (HRT, NFA, OCT) were correlated with
visual field loss in glaucoma. The interindividual variability of NFLT
measurements, among other things, induces limitations on distinguishing beginning
glaucoma from normals. Clinical and scientific significance and future directions
of NFLT measurements are discussed.
PMID- 10180520
TI - Endothelium-derived vasoactive substances relevant to normal-tension glaucoma.
AB - Glaucoma is a progressive optic neuropathy that has a multi-factorial etiology.
The most important risk factor is certainly an increased intraocular pressure.
However, clinical observations have indicated that factors other than increased
intraocular pressure also damage the neural tissue in glaucomatous optic
neuropathy. The most prominent of these to be vascular dysregulation. Vascular
tone is permanently regulated by a number of regulatory systems and factors, and
the endothelial cell layer acts as an important mediator for the response to
these factors. According to recent evidence, glaucomatous optic neuropathy may be
associated with changes in endothelium-dependent vascular regulation.
Consequently, therapeutic approaches based on vasodilator drugs acting via
endothelium-derived substances are being developed. Although promising
preliminary studies have been performed, the clinical relevance of such treatment
remains to be clarified.
PMID- 10180521
TI - Technique and outcome of combined phacoemulsification and trabeculectomy.
AB - The efficacy of combined surgery for the treatment of concurrent glaucoma and
cataract has long been under scrutiny. Comparisons between sequential surgery and
combined procedures have shown mixed results, and current guidelines have been
drawn for the indication of combined surgery. The evolution of combined triple
surgery--cataract extraction, intraocular lens implantation, and filtering
procedure--has evolved from planned extracapsular cataract extraction to small
incision phacoemulsification. The improvements of phacoemulsification over
extracapsular surgery have naturally given rise to improvements in the results of
combined procedures; good outcomes in both intraocular pressure control and
visual acuity have been reported along with low complication rates. The
techniques of combined phacoemulsification-trabeculectomy are under continual
development as new sutureless incisions, filtration procedures, and
antimetabolite use are studied. The results of numerous studies show that the
combined procedure is an effective method of treatment of glaucoma and cataract.
This review examines various recent aspects of the combined procedure,
phacoemulsification-trabeculectomy, antimetabolites, results and complications,
as well as current developments of new techniques. In addition, we review studies
on combined cataract extraction and trabeculectomy, including older literature on
planned extracapsular extraction plus trabeculectomy as well as newer studies on
phacoemulsification-trabeculectomy.
PMID- 10180522
TI - The contribution of phacoemulsification to combined cataract and glaucoma
surgery.
AB - The refinements of small incision cataract surgery by phacoemulsification with
foldable intraocular lens implantation and the pharmacologic modulation of wound
healing have brought new options for the combined procedure. Phacoemulsification
combined with filtering surgery has the potential advantage of requiring a
smaller conjunctival and scleral incision, which may reduce inflammation and bleb
scarring with the possibility of enhanced bleb formation and long-term
intraocular pressure control. The smaller phacoemulsification incision also helps
to reduce postoperative astigmatism and improve visual results. Following
combined phacoemulsification and filtering surgery, a larger area of undisturbed
or virginal tissue in the conjunctiva and at the limbus is spared for further
glaucoma surgeries or revision if the initial procedure fails. The risk of
suprachoroidal hemorrhage during phacoemulsification in this susceptible group of
patients is minimized by maintaining a closed chamber during the procedure.
PMID- 10180523
TI - Accelerating technology transfer: new relationships for academia, industry and
government.
AB - The budget deficit, reduction in Defense spending and the lack of return in the
"peace dividend" has resulted in reduced federal funding for research. A number
of programs have attempted to remedy the problem, with the use of collaborative
funding as one of the major solutions. However, within the medical research
community, there continues to be a very long technology transfer cycle. By
mimicking the processes of non-medical high technology research and employing a
number of these innovative solutions to medical research could afford the pathway
to success. A template of how this could be accomplished through cooperative
efforts of academia, industry and government is presented by using examples of
success and failure in the past.
PMID- 10180524
TI - Computer-assisted image-guided surgery using the Regulus Navigator.
AB - The term "frameless image-guided surgery" has become as well-known to surgeons as
computerized tomography or operating room microscope over the past several years.
The technologies behind this new surgery option include robotic arms, infra-red
camera arrays (1D and 2D), ultrasound, robotic microscopes and magnetic field
digitizers. The authors have shown the magnetic field technology incorporated in
the Regulus Navigator to be a viable, accurate surgeon's tool by first
integrating a conventional framed device and magnetic field frameless device,
then advancing to the frameless device alone. During surgery a patient's anatomy
is first registered to preoperatively acquired radiological data. Surgical
instruments are tracked on interactive CT/MRI displays as the surgeon locates his
point or volume-in-space within the surgical field and uses his own
procedure/technique of choice for surgical treatment. A clinical trial of 221
patients showed an overall mean accuracy of 2.56 mm with a standard deviation of
1.15 mm for intraoperative registration. Major concerns of utilizing magnetic
field technology in the operating room, such as interference from surrounding
metallic objects and equipment, were proven manageable while maintaining
acceptable accuracy.
PMID- 10180525
TI - VIRGY: a virtual reality and force feedback based endoscopic surgery simulator.
AB - This paper describes the VIRGY project at the VRAI Group (Virtual Reality and
Active Interface), Swiss Federal Institute of Technology (Lausanne, Switzerland).
Since 1994, we have been investigating a variety of virtual-reality based methods
for simulating laparoscopic surgery procedures. Our goal is to develop an
endoscopic surgical training tool which realistically simulates the interactions
between one or more surgical instruments and gastrointestinal organs. To support
real-time interaction and manipulation between instruments and organs, we have
developed several novel graphic simulation techniques. In particular, we are
using live video texturing to achieve dynamic effects such as bleeding or
vaporization of fatty tissues. Special texture manipulations allows us to
generate pulsing objects while minimizing processor load. Additionally, we have
created a new surface deformation algorithm which enables real-time deformations
under external constraints. Lastly, we have developed a new 3D object definition
which allows us to perform operations such as total or partial object cuttings,
as well as to selectively render objects with different levels of detail. To
provide realistic physical simulation of the forces and torques on surgical
instruments encountered during an operation, we have also designed a new haptic
device dedicated to endososcopic surgery constraints. We are using special
interpolation and extrapolation techniques to integrate our 25 Hz visual
simulation with the 300 Hz feedback required for realistic tactile interaction.
The fully VIRGY simulator has been tested by surgeons and the quality of both our
visual and haptic simulation has been judged sufficient for training basic
surgery gestures.
PMID- 10180526
TI - VR simulation of abdominal trauma surgery.
AB - In this paper we describe a test-bed we have developed for simulation of
abdominal trauma surgery. The abdominal surgery scene is highly complex and
contains many layers of deformable organs. Representing this layered and
deformable anatomy with models that can interact, be probed and cut presents a
unique challenge. We have met this challenge by applying a variety of technology
advances in deformable models, computer graphics, and force-feedback (haptic)
interfaces.
PMID- 10180527
TI - Validation of virtual reality to teach and assess psychomotor skills in
laparoscopic surgery: results from randomised controlled studies using the MIST
VR laparoscopic simulator.
AB - Objective assessment of surgical technique is currently impossible. A virtual
reality simulator for laparoscopic surgery (MIST VR) models the movements needed
to perform minimally invasive surgery and can generate a score for various
aspects of psychomotor skill. Two studies were performed using the simulator:
first to assess surgeons of different surgical experience to validate the scoring
system; second to assess in a randomised controlled way, the effect of a standard
laparoscopic surgery training course. Experienced surgeons (> 100 laparoscopic
cholecystectomies) were significantly more efficient, made less correctional
submovements and completed the virtual reality tasks faster than trainee surgeons
or non-surgeons. The training course caused an improvement in efficiency and a
reduction in errors, without a significant increase in speed when compared with
the control group. The MIST VR simulator can objectively assess a number of
desirable qualities in laparoscopic surgery, and can distinguish between
experienced and novice surgeons. We have also quantified the beneficial effect of
a structured training course on psychomotor skill acquisition.
PMID- 10180528
TI - The virtual reality arthroscopy training simulator.
AB - Arthroscopy has already become an irreplaceable method in diagnostics. The
arthroscope, with optics and light source, and the exploratory probe are inserted
into the knee joint through two small incisions underneath the patella.
Currently, the skills required for arthroscopy are taught through hands-on
clinical experience. As arthroscopies became a more common procedure even in
smaller hospitals, it became obvious that special training was necessary to
guarantee qualification of the surgeons. On-the-job training proved to be
insufficient. Therefore, research groups from the Berufsgenossenschaftliche
Unfallklinik Frankfurt am Main approached the Fraunhofer Institute for Computer
Graphics to develop a training system for arthroscopy based on virtual reality
(VR) techniques. Two main issues are addressed: the three-dimensional (3-D)
reconstruction process and the 3-D interaction. To provide the virtual
environment a realistic representation of the region of interest with all
relevant anatomical structures is required. Based on a magnetic resonance image
sequence a realistic representation of the knee joint was obtained suitable for
computer simulation. Two main components of the VR interface can be
distinguished: the 3-D interaction to guide the surgical instruments and the 2-D
graphical user interface for visual feedback and control of the session.
Moreover, the 3-D interaction has to be realized by means of Virtual Reality
techniques providing a simulation of an arthroscope and an intuitive handling of
other surgical instruments. Currently, the main drawback of the developed
simulator is the missing of haptic perception, especially of force feedback. In
cooperation with the Department of Electro-Mechanical Construction at the
Technical University Darmstadt a haptic display is designed and built for the VR
arthroscopy training simulator. In parallel we developed a concept for the
integration of the haptic display in a configurable way.
PMID- 10180529
TI - 3D and 4D atlas system of living human body structure.
AB - A reference system for accessing anatomical information from a complete 3D
structure of the whole body "living human", including 4D cardiac dynamics, was
reconstructed with 3D and 4D data sets obtained from normal volunteers. With this
system, we were able to produce a human atlas in which sectional images can be
accessed from any part of the human body interactively by real-time image
generation.
PMID- 10180530
TI - CT-based 3D-planning for dental implantology.
AB - A system for 3D-planning for dental implantology is described. Since exact
knowledge of the position of the nervus alv. inf. is critical, we present an
algorithm for automated detection of this nerve, which requires only very little
initial user interaction. To allow interactive implant placement on comparatively
low-cost pc hardware we developed hybrid visualization techniques, which refrain
from using large texture memory and raster engines.
PMID- 10180531
TI - Experience with MR-guided therapy.
AB - The use of magnetic resonance imaging (MRI) for the real time guidance of
surgical procedures is now undergoing clinical trials. Among the many procedures
explored, open craniotomy neurosurgery appears to be among the most promising.
Over 50 such cases have been done at the Brigham and Women's Hospital (BWH) in
Boston. We review the technical approach used in these and related procedures. We
consider the way in which imaging is used to augment and improve the procedures.
As well, the implications of these protocols for remote diagnosis and telesurgery
are explored. Finally, the implications of this experience for the insertion of
new technology into medicine are discussed.
PMID- 10180532
TI - Brain surgery simulation system using VR technique and improvement of presence.
AB - A computer aided brain surgery system using virtual reality techniques is
developed. This system is aimed to be used to support the surgeons' decision for
the operational strategies, or used in the training of medical students to learn
how to operate the brain surgery for the patients. In constructing the whole
system, high speed graphical computer is equipped. For input 3D data from MRI or
CT are used to display 3D images, HMD (head-mounted display) and 3D CRT display
with glass are equipped. To improve the 3D images, colors and optical properties
of the voxel are refined.
PMID- 10180533
TI - A PC-based surgical simulator for laparoscopic surgery.
AB - Surgical simulators for minimally invasive surgery have been developing in the
1990s. Most of them use high-end UNIX workstations for real-time simulation of
complex human organ models. Only few of them have input devices with force
feedback. Recently, personal computer technologies have made real-time display of
relatively complex models feasible. We are developing an Intel-based laparoscopic
surgical simulator that provides near real-time intuitive interaction between the
trainee and simulated models of human organs. The surgical simulator has a
prototypical scenario of cholecystectomic surgery. It can interactively simulate
the deformation and cutting of cystic duct and vein. In addition, a set of input
devices with force feedback has been designed and tested to imitate the
manipulation of surgical instruments. The input device has five degrees of
freedom and three of them are driven by DC motors to produce force feedback.
PMID- 10180534
TI - Telemedicine: a personal journey.
PMID- 10180535
TI - Bedside wellness--development of a virtual forest rehabilitation system.
AB - The present study aims at the development of a new concept system that will
contribute toward improving the quality of life for bedridden patients and the
elderly. The results of a basic study showed the possibility of a virtual reality
system reducing stress and pain, provided VR sickness does not occur. A Bedside
Wellness System which lets a person experience a virtual forest walk and provides
a facility of rehabilitation was proposed based on the basic study and developed.
An experiment to assess the developed system using healthy subjects was executed.
The data suggested the positive effects of the system; however, some points to be
improved were also extracted. After a few improvements, the system will be
available for clinical use.
PMID- 10180536
TI - Comparing virtual and real worlds for acrophobia treatment.
AB - Traditional treatment of phobias involves a process of gradual exposure to the
feared object. Virtual Reality (VR) environments have been used to effectively
treat phobias by simulating feared situations, yet these initial studies have
been performed by comparing the effect to no-treatment conditions. We are in the
process of comparing VR exposure treatment to "gold-standard" in-vivo exposure
treatment by replicating an actual in-vivo exposure area in a VR model. The
process of controlling for differences between the two environments highlights a
general procedure of selecting elements in virtual environment design, targeted
towards producing particular emotional effects. It also raises questions about
the necessity for highly realistic simulation in VR phobia treatment.
PMID- 10180537
TI - A new project for rehabilitation and psychomotor disease analysis with virtual
reality support.
AB - This paper deals with the project DD1-97, developed inside European Project
VREPAR, for the application of a new equipment for psychomotor disease analysis
and rehabilitation. The small equipment presents a glove for one finger, with
sensors, which detect the movement of the phalanges and the force of the finger
tip on a button. Electromyographs are measuring the nervous signals from flexion
and extension muscles of the finger. In a portable computer a program examines
the signals and elaborates them. The commands for the patient are of 4 kinds:
dynamic motion of the finger; -motion with vision of the finger; -motion without
vision of the finger; -control by the images from virtual reality which
reproduces the "virtual finger". The results with healthy persons show a
distribution in the foreseen range; with disabled person (with Parkinson's
disease) show that virtual reality may support rehabilitation for neuromotor
problems. The equipment is designed with reference to the most modern ergonomic
concepts.
PMID- 10180538
TI - Personal stories within virtual environments: embodiments of a model for cancer
patient information software.
AB - Two new cancer patient information CD-ROMs extend the personal stories within
virtual environments model of cancer patient information developed for Breast
Cancer Lighthouse. Cancer Pain Retreat and Cancer Prevention Park: Games for Life
are intended to inform and inspire users in an emotionally calming and intimately
informative manner. The software offers users an experience--of visiting a
virtual place and meeting and talking with patients and health care
professionals.
PMID- 10180539
TI - The construction of tridimensional representation of body and external reality in
man. The greatest achievement of evolution to date implications for virtual
reality.
AB - Our 3-D Body Representation constructed during development by our Central Nervous
System under the direction of our DNA, consists of a holographic representation
arising from sensory input in the cerebellum and projected extraneurally in the
brain ventricular fluid which has the chemical structure of liquid crystal. The
structure of 3-D holographic Body Representation is then extrapolated by such
cognitive instruments as boundarization, geometrization and gestalt organization
upon the external environment which is perceived consequently as three
dimensional. When the Body Representation collapses as in psychotic panic states.
patients become terrified as they suddenly lose the perception of themselves and
the world around them as three dimensional, solid in a reliably solid environment
but feel suddenly that they are no longer a person but a disorganized blob. In
our clinical practice we found serendipitously that the structure of three
dimensionality can be restored even without medication by techniques involving
stimulation of the body sensory system in the presence of a benevolent
psychotherapist. Implications for Virtual Reality will be discussed.
PMID- 10180540
TI - A comparative analysis of integrating visual representations with haptic
displays.
AB - As further advances in visual display technologies and force feedback devices are
integrated in virtual systems, questions remain: What level of reality does the
system provide to the user? Is the environment convincing enough to engage the
user and to maximize transfer? Are the visual and haptic displays fully
integrated to provide seamless operation in the simulated environment? Does the
system provide not only the ability to navigate through a simulated environment,
but also realistic interaction with instrumentation and structures? We report on
our advances in developing a virtual simulation system for training in functional
endoscopic sinus surgery (FESS). Specifically, we will present work on subject
trials exploring the realism provided by integrated visual and haptic displays,
and compare and contrast surface vs. volume representation for presenting
realistic models of the anatomy for surgical interaction.
PMID- 10180541
TI - Review of orthopaedic manipulator arms.
AB - Trajectory planning and implementation forms a substantial part of current and
future orthopaedic practice. This type of surgery is governed by a basic
orthopaedic principle [1] which involves the placement of a surgical tool at a
specific site within a region, via a trajectory which is planned from X-ray based
2D images and governed by 3D anatomical constraints. The accuracy and safety of
procedures utilising the basic orthopaedic principle depends on the surgeon's
judgement, experience, ability to integrate images, utilisation of intra
operative X-ray, knowledge of anatomical-biomechanical constraints and eye hand
dexterity. The surgeon must remain as the responsible medical expert in charge of
the overall system. At the same time the surgeon covets the accuracy offered by
Computer Assisted Surgery including a manipulator. A summary of current
inadequacies of manipulators indicates that the main drivers for future work are
that accuracy is critical in close contact with the environment, safety concerns
dictate manipulator geometry and technological limitations are many. In any
effort to develop an optimal manipulator to guide surgical instruments and tools
it is an obvious first step to review and categorise current manipulators. The
aim of this paper is to review all aspects of manipulator design against the five
main criteria of ergonomics; safety; accuracy; sterility and measurable benefits
such as reduced operative time, reduced surgical trauma and improved clinical
results.
PMID- 10180542
TI - Planning and simulation of medical robot tasks.
AB - Complex techniques for planning and performing surgery revolutionize medical
interventions. In former times preoperative planning of interventions usually
took place in the surgeons mind. Today's new computer techniques allow the
surgeon to discuss various operation methods for a patient and to visualize them
three-dimensionally. The use of computer assisted surgical planning helps to get
better results of a treatment and supports the surgeon before and during the
surgical intervention. In this paper we are presenting our planning and
simulation system for operations in maxillo-facial surgery. All phases of a
surgical intervention are supported. Chapter 1 gives a description of the medical
motivation for our planning system and its environment. In Chapter 2 the basic
components are presented. The planning system is depicted in Chapter 3 and a
simulation of a robot assisted surgery can be found in Chapter 4. Chapter 5
concludes the paper and gives a survey about our future work.
PMID- 10180543
TI - Motion feedback as a navigation aid in robot assisted neurosurgery.
AB - This paper describes a test prototype for precision robot-assisted surgery using
a hexapod operating robot and a movable operating cockpit. The objective of the
work described is twofold: 1) To evaluate the use of hexapod robots for precisely
manipulating endoscopes and surgical instruments in sub-millimeter surgery. 2) To
test a new user interface concept based on motion feedback. This paper gives an
overview of the system components and the user interface concept, and reports
results from initial tests. Finally, the paper investigates potential
applications and areas for further development.
PMID- 10180544
TI - A system for robot assisted maxillofacial surgery.
AB - In maxillofacial surgery the quality of the surgical outcome mainly depends on
the experience of the operating surgeon. Thus we intend to support the surgeon
before and during surgery in order to enhance the surgical results. On the one
hand this implies the use of image processing, three dimensional modelling
techniques and visualization techniques of medical image data, on the other hand
planning systems, intraoperative navigation devices and surgical robots are
needed. In this paper a complex expert system is presented, which uses a planner
for generating treatment plans, an infrared navigation for monitoring both
patient, robot, and surgical tool, and a surgical robotic system in order to work
on bone. Special stress is laid on the architecture of the planning system, the
structure of the treatment plans, and the intraoperative communication protocols.
PMID- 10180545
TI - Simulator for virtual surgery using deformable organ models and force feedback
system.
AB - This paper describes a real-time surgery planning system using virtual reality
techniques. This system allows us to simulate incision of skin and organs which
respond as elastic objects with surgical tools in virtual space. Inner structures
such as blood vessels and lesions can be seen and manipulated in the simulation.
In addition to these functions we attempted to add a feedback function that
responds to the operator's hands. We developed a force feedback device to
manipulate the elastic organ model based on pressure from the operator's fingers.
PMID- 10180546
TI - 3D-brain 2.0--narrowing the gap between personal computers and high end
workstations.
AB - Recent advances in personal computer hardware and software have pushed the
graphic capacity of these easier to use and, more importantly, cheaper computers
to a level approximating the current standard of high end workstations. The
interactivity and graphic complexity of a modern PC is rapidly approaching the
current standard on Silicon Graphics (although with respect to texture mapping,
the SGI is still ahead of the PCs). The modern medical student laboring under
increasingly higher demands with respect to versatility, not only in basic
science and traditional medical knowledge, is also faced with the requirement to
learn and understand modern scientific visualization and analytical instruments.
Furthermore, basic knowledge of information technology and computer literacy is
expected of the next generation medical professionals. These demands forces
medical schools to increasingly invest in computers and information technology
for educational purposes. Due to common class sizes, these computers are most
commonly Windows PCs or Apple Macintoshes. For distance education, telematics or
studies at home, personal computer versions of the workstation graphics are a
necessity. 3D-Brain 2.0 is an educational software package intended to run on
basic personal computers and utilizing modern software technologies such as
QuickTime VR 2.0 and VRML 2.0, to provide the students with insight into modern
clinical and scientific visualization, focusing on the anatomy and functionality
of the human brain. The aim of this paper to test the validity and usefulness of
these new visualization techniques. METHODS: 3D-Brain is based on human brains
sliced in 1 mm sections (NB. NOT based on NLMs Visual Human). Each slice was
photographed, digitized, optimized and aligned using proprietary software. The
datasets were then created by manual tracing followed by triangulation, smoothing
and 3D visualization using Silicon Graphics computers. For the QuickTime VR
project, 684 images with a 10 degrees angle were generated for each scene and
ported to an Apple Macintosh computer for further manipulation. VRML code was
generated directly from the original dataset. All interactivity was programmed on
a Macintosh and subsequently ported to the Windows95 PC platform. The minimum
requirements to run the software are either a PowerPC based Macintosh computer or
a Pentium based Windows 95 computer with 16 Mb, 16 bit display and a 4 speed CD
ROM. RESULTS AND DISCUSSION: 3D-Brain 2.0 provides medical students at Goteborg
University the means to complement traditional teaching using visualization
techniques and three-dimensional models. These techniques also serve as an
insight into the different clinical means of visualization the student will
encounter throughout his/her continued education and professional career. For
educational purposes, it has been established that among the tested new
visualization techniques, CD-ROM based software utilizing QTVR is still the best
methodology to use for pedagogical software. VRML shows promise in porting these
software packages to the Web while Open Inventor is the preferred format for
research purposes.
PMID- 10180547
TI - The Virtual Instrumentation (VI) Laboratory facilitates customized on-site
ergonomic analysis of minimally invasive surgery.
AB - Ergonomic studies are needed to understand and improve the visual and physical
interface that minimally invasive surgery methods interpose between the surgeon
and the operating field. We used the Virtual Instrumentation (VI) Laboratory of
the Biomedical Engineering Program at California State University, Sacramento to
develop a portable ergonomic analysis system to compare the physical workloads
imposed on the surgeon by tradition open and laparoscopic surgery techniques. We
used the system at a national surgery conference to measure electromyogram (EMG)
activity from thumb and forearm muscles of volunteer subjects as they performed
simulated surgical tasks using open and laparoscopic techniques. We found that
EMG activity was significantly greater for the laparoscopic than for the open
surgery technique, suggesting that the laparoscopic technique was more physically
demanding. The portable ergonomic analysis VI system was quick to set up and
convenient to use. We are using the rapid prototyping and modular design
capabilities of the VI Lab to develop additional ergonomic analysis VI systems.
PMID- 10180548
TI - A non-intrusive display technique for providing real-time data within a surgeons
critical area of interest.
AB - Modern surgeons have at their disposal a vast array of advanced technological
data dissemination devices. The ring of high resolution monitors circling the
typical operating area to display pre-operative and real-time patient data is
esteemly supportive. The drawback, however, is that such displays require the
surgeons to frequently shift their head and gaze away from the principle field of
interest. We describe a new display technique that provides surgeons with a
lightweight, wearable display surface that permits localization of medical data
of main interest near the field of operation with minimal head and gaze
movements.
PMID- 10180549
TI - The virtual retinal display: a new technology for virtual reality and augmented
vision in medicine.
AB - INTRODUCTION: The Virtual Retinal Display (VRD) is a new technology for creating
visual images. It was developed at the Human Interface Technology Laboratory (HIT
Lab) by Dr. Thomas A. Furness III. The VRD creates images by scanning low power
laser light directly onto the retina. This special method results in images that
are bright, high contrast and high resolution. In this paper, we describe how the
VRD functions, the special consequences of its mechanism of action and potential
medical applications of the VRD, including surgical displays and displays for
people with low vision. A description of its safety analysis will also be
included. In one set of tests we had a number of patients with partial loss of
vision view images with the VRD. There were two groups of subjects: patients with
macular degeneration, a degenerative disease of the retina and patients with
keratoconus. Typical VRD images are on the order of 300 nanowatts. VRD images are
also readily viewed superimposed on ambient room light. In our low vision test
subjects, 5 out of 8 subjects with macular degeneration felt the VRD images were
better and brighter than the CRT or paper images and they were able to reach the
same or better level of resolution. All patients with Keratoconus were able to
resolve lines of test several lines smaller with the VRD than with their own
correction. Further, they all felt that the VRD images were sharper and easier to
view. The VRD is a safe new display technology. The power levels recorded from
the system are several orders below the power levels prescribed by the American
National Standard. The VRD readily creates images that can be easily seen in
ambient roomlight and it can create images that can be seen in ambient daylight.
The combination of high brightness and contrast and high resolution make the VRD
an ideal candidate for use in a surgical display. Further, tests show strong
potential for the VRD to be a display technology for patients with low vision.
PMID- 10180550
TI - A sensate liner for biomedical monitoring applications.
AB - This program develops and demonstrates technologies useful for implementing a
manageable cost effective systems approach to monitoring the medical condition of
personnel by way of an instrumented uniform hereafter referred to as a Sensate
Liner (SL). The SL consists of a form fitting garment which contains and
interconnects sensing elements and devices to an electronics pack containing a
processor and transmitter. The SL prototype requires fiber, textile, garment and
sensor development. The SL textile consists of a mesh of electrically and
optically conductive fibers integrated into the normal structure (woven or
knitted) of fibers and yarns selected for comfort and durability. A suite of SL
garment compatible embedded biological and physical sensors are then integrated
into the SL. The initial SL sensor suite is selected to improve triage for combat
casualties. Additional SL sensor concepts for medical monitoring will be
discussed.
PMID- 10180551
TI - Computerized endoscopic surgical grasper.
AB - We report a computerized endoscopic surgical grasper with computer control and a
force feedback (haptic) user interface. The system uses standard unmodified
grasper shafts and tips. The device can control grasping forces either by direct
surgeon control, via teleoperation, or under software control. In this paper, we
test an automated palpation function in which the grasper measures mechanical
properties of the grasped tissue by applying a programmed series of squeezes.
Experimental results show the ability to discriminate between the normal tissues
of small bowel, lung, spleen, liver, colon, and stomach. We anticipate
applications in telesurgery, clinical endoscopic surgery, surgical training, and
research.
PMID- 10180552
TI - 3D visual presentation of shoulder joint motion.
AB - The 3D visual presentation of biodynamic events of human joints is a challenging
task. Although the 3D reconstruction of high contrast structures from CT data has
been widely explored, then there is much less experience in reconstructing the
small low contrast soft tissue structures from inhomogeneous and sometimes noisy
MR data. Further, there are no algorithms for tracking the motion of moving
anatomic structures through MR data. We represent a comprehensive approach to 3D
musculoskeletal imagery that addresses these challenges. Specific imaging
protocols, segmentation algorithms and rendering techniques are developed and
applied to render complex 3D musculoskeletal systems for their 4D visual
presentation. Applications of our approach include analysis of rotational motion
of the shoulder, the knee flexion, and other complex musculoskeletal motions, and
the development of interactive virtual human joints.
PMID- 10180553
TI - Development of the force-feedback model for an epidural needle insertion
simulator.
AB - The Ohio Supercomputer Center and the Department of Anesthesiology at the OSU
Medical Center have developed a computer-based simulation system for use in
training anesthesiology residents in the technique of placing a needle for an
epidural block. Although the simulator has been well regarded, the fidelity of
the haptic feedback is limited because it is based on subjective expert-user
evaluation and not on objective model-based or data-based empirical methods. Only
a single degree of freedom for force-feedback is required. However, the
simulation must be able to accurately portray the force required to puncture each
layer of tissue in order to feel realistic. The purpose of the research described
in this paper was to devise a methodology for creating empirically based
realistic force-feedback models for the epidural needle insertion procedure using
MRI data and biomechanical data from materials testing.
PMID- 10180554
TI - A new imaging paradigm for medical applications.
PMID- 10180555
TI - A theoretical comparison of 2-camera and 3-camera optical localizers with active
or passive instrumentation.
AB - Since the technology was first pioneered in the medical arena in the early 1990s,
optical localizers have increasingly been used in computer assisted surgical
procedures. This surgical practice is commonly referred to as "Image Guided
Surgery (IGS)". Historically, mechanical stereotactical frames have been used for
3-D position measurement in surgery. Now, new computer input devices can generate
high speed numeric position data for direct input into a host computer. This
enables application software to acquire the real-time position of surgical
instruments and display the positions relative to previously acquired Computer
Tomography (CT) or Magnetic Resonance (MR) images on the same computer screen. In
addition to optical, there are currently three other types of technologies
utilized in the design of these localizers--mechanical, magnetic and sonic. Of
these four technologies, optical has emerged as the leader due to its superior
accuracy, ease of use, and unobtrusive design. This document focuses on optical
localizer technology, specifically comparing 2-camera, or 2-sensor, systems with
3-camera, or 3-sensor, systems. Figures 1 and 2 show applications of such IGS
workstations in cranial surgery.
PMID- 10180556
TI - Training environment for inferior vena caval filter placement.
AB - This paper describes a Virtual Environment system designed to aid in training
interventional radiologists in inferior vena cava filter placement. It is being
developed as part of a VE simulator for a number of surgical and interventional
radiology procedures at the Laboratory for Advanced Computer Applications in
Medicine at the George Washington University. In this procedure a filter is
placed in the inferior vena cava to prevent blood clots from the lower portion of
the body from reaching the lungs and causing a pulmonary embolus. The simulation
is designed to provide both tutorial and testing modes for the filter placement
procedure.
PMID- 10180557
TI - UltraTrainer--a training system for medical ultrasound examination.
AB - This paper introduces the prototype of the computer program UltraTrainer, which
could simplify the education and training of physicians working with medical
ultrasound systems. The UltraTrainer replaces probe and patient by a magnetical
tracking system and 3D-data from a real examination, which are registered with a
phantom. In this way the UltraTrainer makes a simulation of the real ultrasound
examination possible, which can be useful for students and physicians. This paper
describes the system components and gives an overview of potential applications.
PMID- 10180558
TI - A commercially viable virtual reality knee arthroscopy training system.
AB - Arthroscopy is a minimally invasive form of surgery used to inspect joints. It is
complex to learn yet current training methods appear inadequate, thus negating
the potential benefits to the patient. This paper describes the development and
initial assessment of a cost-effective virtual reality based system for training
surgeons in arthroscopy of the knee. The system runs on a P.C. Initial
assessments by surgeons have been positive and current developments in deformable
models are described.
PMID- 10180559
TI - Virtual medical trainer. Patient assessment and trauma care simulator.
AB - The Virtual Medical Trainer (VMET) combines multimedia sound and graphics with
physiological engines, medical-procedures databases, and 3-D patients to produce
an interactive environment that can mimic the cognitive pre-hospital assessment
and care demands of a real emergency. VMET uses a reconfigurable component
software and training framework that allows a uniform user interface, ease of
increasing training complexity, and expansion of the software components. VMET
provides an opportunity to experience a range of trauma scenarios prior to the
challenge of an actual trauma situation.
PMID- 10180560
TI - Virtual environments for training critical skills in laparoscopic surgery.
AB - Surgical training simulations must incorporate not only advanced technical
features, such as detailed geometric organ models and physically-based modeling
techniques, but also a thorough understanding of the major training issues
relating to a particular procedure. We have developed a prototype environment for
training laparoscopic cholecystectomy, or gallbladder removal surgery, which
focuses a student's attention on the critical steps performed during the
procedure and provides feedback as to the common errors committed during a
session. The current version of our system runs in real-time on a mid-range
graphics workstation. The simulation also provides a platform for research into a
variety of different areas, including tissue modeling, finite element methods,
and generalized simulation authoring.
PMID- 10180561
TI - A national center for biocomputation: in search of a patient-specific interactive
virtual surgery workbench.
AB - This report describes the three-dimensional imaging and virtual environment
technologies developed in NASA's Biocomputation Center for scientific purposes
that have now led to applications in the field of medicine. A major goal is to
develop a virtual environment surgery workbench for planning complex craniofacial
and breast reconstructive surgery, and for training surgeons.
PMID- 10180562
TI - Virtual jaw: a 3D simulation for computer assisted surgery and education.
AB - The jaw is one of the most complex joints in the human body. Its sliding and
gliding movements are difficult to understand. Therefore, up to now there exist
only mechanical simulations. But there is a strong need for a computer model of
the jaw--the virtual jaw--to support physicians and surgeons in diagnoses and
preoperative planning. During the preoperative planning of craniofacial
operations for example, individual patient data has to be examined and the
operation has to be simulated. In the education of physicians such a simulation
system gives a much better understanding of the anatomy and functionality of the
jaw than static images in text books do. The paper presents a 3D simulation of
the human mastication apparatus which can be used for the preoperative planning
of craniofacial surgeries as well as the education of dentists and surgeons. It
consists of three interacting components: A kinematic model which defines the
constraints of the articulation, a model for the mastication muscles and a 3D
graphical interface.
PMID- 10180563
TI - Assessing a VR-based learning environment for anatomy education.
AB - The purpose of the research proposed herein is to develop an empirical,
methodological tool for the assessment of visual depth perception in virtual
environments (VEs). Our goal is to develop and employ a behaviorally-based method
for assessing the impact of VE design features on the perception of visual depth
as indexed by the performance of fundamental perceptual-motor activities.
Specifically, in this experiment we will assess the affect of two dimensions of
VE system design--(1) viewing condition or "level of immersion", and (2)
layout/design of the VE--on the performance of an engaging, game-like task. The
characteristics of the task to be employed are as follows--(1) it places no
demands on cognition in the form of problem solving, retrieval of previously
learned information, or other analytic activity in order to assure that (2)
variations in task performance can be exclusively attributed to the extent to
which the experimental factors influence visual depth perception. Subjects'
performance will be assessed in terms of the speed and accuracy of task
performance, as well as underlying dimensions of performance such as workload,
fatigue, and physiological well being (i.e., cybersickness). The results of this
experiment will provide important information on the effect of VE immersion and
other VE design issues on human perception and performance. Further development,
refinement, and validation of this behaviorally-based methodology will be pursued
to provide user-centered design criteria for the design and use of VE systems.
PMID- 10180564
TI - Medical volume rendering over the WWW using VRML and JAVA.
AB - The rapid growth of the World Wide Web (WWW) enables access to huge amounts of
data and applications. The diversity of data-structures and applications has led
to the concept of network computing where the data is encapsulated within the
application. The end-user does not have to worry about tools for data
manipulation as they are bundled together with the data itself. However, the user
usually has to pay a price in the form of degraded performance. While JAVA is
gradually taking its place as the network cross platform programming language, it
is clear that it currently does not support high-performance visualization. The
purpose of this paper is to demonstrate that high performance volume rendering,
traditionally reserved for high-end visual computing, can now be made widely
available in a cross-platform fashion using VRML and JAVA.
PMID- 10180565
TI - The clinical advantages of editable real-time volume rendering in a medical
virtual environment: VolMed.
AB - Segmentation for a medical virtual environment is a process of image diagnosis.
It should be performed by clinical doctors, otherwise the data may be meaningless
for using clinical purposes. At the National Cancer Center, in Japan, we have
recently developed interactive, editable real-time volume rendering software
(VolMed), based on Volren-6 software, with the ability to interactively edit the
3D images of a patient's virtual cancer and virtual organs, in a virtual
environment. Doctors can see proposed solutions to clinical problems as 3D
images, using real-time volume rendering. We conclude that interactive editing is
very important for clinical use, and also decreases the time required to create
the virtual cancer images used for surgical simulation, pre-surgical planning and
3D invasion diagnoses.
PMID- 10180566
TI - The virtual temporal bone.
AB - The human temporal bone is a 3-dimensionally complex portion of the skull that
contains delicate and vital anatomic structures imbedded within dense bone.
Current teaching tools have proven to be only marginally adequate for the needs
of the aspiring otologic surgeon in learning this anatomy. A variety of image
processing and reconstruction techniques were used to reconstruct an anatomically
accurate 3-dimensional model of the human temporal bone from serial histologic
sections. Using CAVE technology, the model can be manipulated in a stereoscopic
virtual environment so that it can be studied from any viewpoint, greatly
simplifying the task of learning this anatomy. Applications in surgical planning
and Internet based teaching are discussed.
PMID- 10180567
TI - Knowledgebased segmentation.
AB - The segmentation of medical images like CT or MRI scans represents a great
challenge to researchers in computer vision, due to the variability of the
individual anatomy and the different characteristics of the scanning systems. As
an anatomical knowledge base improves the recognition of structures in CT or MRI
scans, we chose a knowledge based segmentation in our approach, which will be
explained in the following.
PMID- 10180568
TI - Generating finite element models from volumetric medical images.
AB - For planning and simulating of surgical interventions geometric models have to be
generated from medical images. In this paper, we will present a new method for
generating finite element meshes from volumetric images. The method is designed
to capture even very small anatomic structures, while the mesh density can be
controlled and locally increased.
PMID- 10180569
TI - Advanced 3D-visualization, including virtual reality, distributed by PCs, in
brain research, clinical radiology and education.
PMID- 10180570
TI - Computer in the O.R. for quality control. Intraoperative data acquisition model
for laparoscopy.
PMID- 10180571
TI - Trans-telephonic electro-cardiographic monitoring (TTEM)--first Indian
experience.
AB - Trans-Telephonic Electro-Cardiographic Monitoring (TTEM) centre, is an easy to
use tool, now freely available in India. Between May 1996 and May 1997, 398
patients were registered at Escorts Heart Alert Centre (EHAC) for TTEM; 321 (81%)
males and 77(19%) females. Age range was from 1 month to 95 years 65% patients
were from New Delhi; 35% from other cities in India and abroad. Patients'
clinical profile were post-CABG, post-PTCA, post-MI, patients after discharge;
evaluation of chest pain, palpitation, chronic angina, arrhythmias, and pace
maker follow up. Out of 664 symptomatic transmissions, 510 (77%) were for cardiac
symptoms like chest pain 309 (61%); palpitation 90 (18%); uneasiness 61(12%);
dizziness 28(5%) breathlessness 22(4%). 154(23%) were for non-cardiac symptoms
like stitch pain and backache (51); Atypical chest pain (39); weakness and fever
(45) and sweating (19). 84%, 78% and 75% patients of chest pain, palpitation and
dizziness respectively transmitted their ECGs within one hour of the onset of the
symptoms. Out of 664 symptomatic transmissions, 531 required either re-assurance
or drug-dose adjustment on telephone. 97 were called to OPD on elective basis. 36
patients were advised immediate hospitalization, for acute management. TTEM was
useful in avoiding 628 unnecessary visits to the hospital whereas 36 patients,
were immediately hospitalized, for receiving acute life-saving interventions.
PMID- 10180572
TI - Videoconferencing as a medical educational tool: first experience in Argentinean
public hospital.
AB - Authors present their experience with first medical videoconferencing program
developed in a public Argentinean hospital. Both modalities--room and desktop
videoconferencing--were used. The program was exclusively used for educational
purposes. A total of twelfth videoconferencing were successfully made using all
resources. They included surgical procedures, magisterial lessons, grand rounds,
etc. The project proved that videoconferencing is a cost-effective medical
education tool, even in developing countries.
PMID- 10180573
TI - Modeling of a knee joint for the VRDA tool.
AB - We propose in this paper a novel method for the modeling of the motion of
anatomical joints. The method is based on collision detection and knowledge of
biomedical experimental data.
PMID- 10180574
TI - A window on regional cerebral blood flow via voluntary hand activity using a
whole hand input in a virtual environment.
PMID- 10180575
TI - Information frames: a new multimedia approach to Web-based learning of biology
and medicine.
AB - Presentation of content in hyperlinked multimedia formats for teaching has failed
using the computer's power of navigation through rich visual and auditory
information. We have developed "Information Frames", an authoring tool in
hypertext markup language (html) format, that allows easy utilization by
technology-challenged teachers and professors, and attracts students because of
interactive, design-based learning. An Information Frame contains a definition,
explanation and illustration of a single concept. Topics are provided with
hyperlinks to other Information Frames having related concepts that may provide
prerequisite knowledge, or may raise the concept to a more integrative level. A
graphical view of the linked-Information Frames presents a Concept Map of the
overall topic.
PMID- 10180576
TI - Building a virtual invasive patient on a budget.
AB - Virtual Reality shows promise as a valuable tool in medical research and
training, but one of the factors limiting the expansion potential of such
technology is cost of both hardware and software. This paper describes a proof-of
concept project whose aim was to design and implement a generic VR simulation
system using low cost hardware and free software.
PMID- 10180577
TI - Development and evaluation of a spine biopsy simulator.
AB - A spine biopsy simulator is being developed to 1) train surgeons on the current
method for CT-directed needle biopsy and 2) provide a testbed for developing new
image-guided and robot-assist methodologies. A task analysis and function
allocation assessment provide the needed information for the first stage of the
simulator development and evaluation.
PMID- 10180578
TI - Implications of 3D visualization for medical education.
PMID- 10180579
TI - Simulation technology in surgical education: can we assess manipulative skills
and what does it mean to the learner.
PMID- 10180580
TI - Modern cosmology and the origin of our three dimensionality.
AB - We are three dimensional egocentric beings existing within a specific space/time
continuum and dimensionality which we assume wrongly is the same for all times
and places throughout the entire universe. Physicists name Omnipoint the origin
of the universe at Dimension zero, which exploded as a Big Bang of energy
proceeding at enormous speed along one dimension which eventually curled up into
matter: particles, atoms, molecules and Galaxies which exist in two dimensional
space. Finally from matter spread throughout the cosmos evolved life generating
eventually the DNA molecules which control the construction of brains complex
enough to construct our three dimensional Body Representation from which is
extrapolated what we perceive as a 3-D universe. The whole interconnected
structures which conjure up our three dimensionality are as fragile as Humpty
Dumpty, capable of breaking apart with terrifying effects for the individual
patient during a psychotic panic, revealing our three dimensionality to be but
"maya", an illusion, which we psychiatrists work at putting back together.
PMID- 10180581
TI - Force interactions in laparoscopic simulations: haptic rendering of soft tissues.
AB - Research in the area of computer assisted surgery and surgical simulation has
mainly focused on developing 3D geometrical models of the human body from 2D
medical images, visualization of internal structures for educational and
preoperative surgical planning purposes, and graphical display of soft tissue
behavior in real time. Conveying to the surgeon the touch and force sensations
with the use of haptic interfaces has not been investigated in detail. We have
developed a set of haptic rendering algorithms for simulating "surgical
instrument--soft tissue" interactions. Although the focus of the study is the
development of algorithms for simulation of laparoscopic procedures, the
developed techniques are also useful in simulating other medical procedures
involving touch and feel of soft tissues. The proposed force-reflecting soft
tissue models are in various fidelities and have been developed to simulate the
behavior of elastically deformable objects in virtual environments. The developed
algorithms deal directly with geometry of anatomical organs, surface and
compliance characteristics of tissues, and the estimation of appropriate reaction
forces to convey to the user a feeling of touch and force sensations.
PMID- 10180582
TI - Formative design of a virtual learning environment.
AB - Current technology for 3D visualization, modeling and interaction allows the
construction of attractive virtual environments for study of anatomy, surgery and
other biomedical fields. The formative methodology for designing such
environments is uncharted, but necessary before committing to large scale
development. We present one such methodology undertaken during the design of a
learning environment for biology for high school and middle school students. We
expect to extend this design methodology to the development of environments for
the teaching of medical subjects.
PMID- 10180583
TI - Validation of the Madigan ESS simulator.
AB - The Madigan Endoscopic Sinus Surgery (ESS) Simulator, developed by a multi
institution team led by Lockheed Martin, includes force-feedback instrument and
virtual endoscope interaction with three-dimensional paranasal anatomy models
derived from the Visible Human dataset, supplemented by a variety of graphical
and auditory instructional aids embedded in the model. Our formal evaluation of
Version 1.2 of the system focused on its validity as an ESS simulator. Run-time
and survey data were collected for three groups of subjects on a common protocol
progressing through the three basic ESS subtasks: navigation, injection, and
dissection. Non-MD subjects performed the tasks on a simplified abstract virtual
model with instructional aids (hoops for the navigation path, injection targets,
dissection spheres, auditory feedback about task completion, and simulated
patient heart rhythm). Non-ENT MDs progressed from this "novice" model to a
simulated anterior ethmoidectomy on an "intermediate" model with the aids
embedded in the reconstructed and segmented paranasal anatomy. Otolaryngologists
ranging from second-year ENT residents through senior staff progressed through
both the abstract and intermediate models, and then performed the simulated
surgical procedure on an "advanced" model, consisting of the anatomy with no
instructional aids. The procedural validity of the simulator is supported by a
strong correlation between performance on the simulator and degree of prior ESS
experience, by convergent correlation among independent measures of subject task
performance, and by subjective evaluations by experienced ESS surgeons.
PMID- 10180585
TI - Telemedicine in prison.
PMID- 10180584
TI - International surgical telementoring: our initial experience.
AB - INTRODUCTION: Telesurgical laparoscopic telementoring has successfully been
implemented between the Johns Hopkins Bayview Medical Center and the Johns
Hopkins Hospital in 27 prior operations. In this previously reported series,
telerobotic mentoring was achieved between two institutions 3.5 miles away. We
report our experience in performing two international surgical telementoring
operations. PURPOSE: To determine the clinical utility of international surgical
telementoring during laparoscopic surgical procedures. METHOD: A laparoscopic
adrenalectomy was telementored between Innsbruck, Austria (5,083 miles) and
Baltimore, MD. As well, a laparoscopic varicocelectomy was telementored between
Bangkok, Thailand and Baltimore, MD (10,880 miles) both over three ISDN lines
(384 kbps) with an approximate 1 sec delay. RESULTS: Both procedures were
successfully accomplished with an uneventful postoperative course. CONCLUSION:
International telementoring is a viable method of instructing less experienced
laparoscopic surgeons through potentially complex laparoscopic procedures, as
well as potentially improving patient access to specialty care.
PMID- 10180586
TI - Web-based segmentation and display of three-dimensional radiologic image data.
AB - In many clinical circumstances, viewing sequential radiological image data as
three-dimensional models is proving beneficial. However, designing customized
computer-generated radiological models is beyond the scope of most physicians,
due to specialized hardware and software requirements. We have created a simple
method for Internet users to remotely construct and locally display three
dimensional radiological models using only a standard web browser. Rapid model
construction is achieved by distributing the hardware intensive steps to a remote
server. Once created, the model is automatically displayed on the requesting
browser and is accessible to multiple geographically distributed users.
Implementation of our server software on large scale systems could be of great
service to the worldwide medical community.
PMID- 10180587
TI - ATTRACT--applications in telemedicine taking rapid advantage of cable television
network evolution.
AB - ATTRACT is a project that intends to provide telemedicine services over Cable
Television Networks. ATTRACT is an European Commission funded project (Healthcare
Telematics). The main objective of ATTRACT is to take advantage of emerging
European Cable Television network infrastructures and offer cost-effective care
to patients at home. This will be achieved through a set of broadband network
applications that competitively provide low cost interactive health-care services
at home. The applications will be based on existing or developing European Cable
Television network infrastructures in order to provide all kind of users with
affordable homecare services. It is ATTRACT's intention that citizens and users
benefit from high quality access to home telemedical services which also implies
cost savings for patients, their families and the already over burdened health
institutions. In addition, the European industries will have extensive
opportunities to develop, evaluate and validate broadband network infrastructures
providing multimedia and interactive telemedical services at home. ATTRACT
contributes to the EU telecommunications and telematics policy objectives that
promote the development and validation of "applications and services" which
"provide an intelligent telematic environment for the patient in institutions and
other points of care that helps the patient to continue, as far as possible,
normal activities and external communication".
PMID- 10180588
TI - A patient-centric approach to telemedicine database development.
AB - Computer and telecommunications technologies have unleashed a wide range of
powerful tools for gathering, storing, and distributing patient information.
Computerized records enable healthcare providers to rapidly access patient data
and to closely monitor patients from a distance. These significant advantages can
be further extended by using the technology to more fully involve patients in
their own healthcare management. A patient-centric approach to telemedicine means
that the patient takes on additional responsibility and control, and the benefits
from increased patient involvement will translate into improved compliance,
reduced litigation, lower costs, and better outcomes. Furthermore, there are
often important ethical questions that are best decided by the informed patient.
Patients have a right to know what information is being gathered and who will be
authorized to access that information. Current health information systems do not
adequately address these issues, and telemedicine applications--particularly home
based telemedicine--is forcing everyone to take a closer look at patients' roles
in their own healthcare. In this presentation, a patient-centric home
telemedicine database is described, the limitations are discussed, and future
directions are proposed.
PMID- 10180589
TI - An immersive environment for the direct visualization and segmentation of
volumetric data sets.
AB - This paper describes a software environment for visualizing and segmenting
volumetric data sets such as CT, MRI and the Visible Human data set. The goal is
to produce an intuitive environment where the expert knowledge of the end user
can be employed to directly guide visualization and segmentation of the data. The
environment is built around the Fakespace Immersive Workbench (TM), which
provides the user with the illusion that the data set volume resides in the space
directly above the workbench surface. Using a position/orientation-tracked probe
the user is able to interact with the visualization algorithm and segment the
data set to expose features of interest. Segmentation can be performed in either
the ray space of the volume rendering algorithm or the coordinate space of the
data volume itself. The segmentation results can be saved and used for other
purposes including the construction of polygonal models.
PMID- 10180590
TI - Secured medical imaging over the Internet.
AB - The Internet has established itself as an affordable, extremely viable and
ubiquitous communications network that can be easily accessed from virtually any
point in the world. This makes it ideally suited for medical image
communications. Issues regarding security and confidentiality of information on
the Internet, however, need to be addressed for both occasional, individual users
and consistent enterprise-wide users. In addition, the limited bandwidth of most
Internet connections must be factored into the development of a realistic
usermodel and resulting protocol. Open architecture issues must also be
considered so that images can be communicated to recipients who do not have
similar programs. Further, application-specific software is required to integrate
image acquisition, encryption and transmission into a single, streamlined
process. Using Photomailer software provided by PhysiTel Inc., the authors
investigated the use of sending secured still images over the Internet. The scope
of their investigation covered the use of the Internet for communicating images
for consultation, referral, mentoring and education. Photomailer software was
used at several local and remote sites. The program was used for both sending and
receiving images. It was also used for sending images to recipients who did not
have Photomailer, but instead relied on conventional email programs. The results
of the investigation demonstrated that using products such as Photomailer, images
could be quickly and easily communicated from one location to another via the
Internet. In addition, the investigators were able to retrieve images off of
their existing email accounts, thereby providing greater flexibility and
convenience than other systems which require scheduled transmission of
information on dedicated systems. We conclude that Photomailer and similar
products may provide a significant benefit and improve communications among
colleagues, providing an inexpensive means of sending secured images on the
Internet.
PMID- 10180591
TI - Demonstration of surgical telerobotics and virtual telepresence by Internet +
ISDN from Monterey (USA) to Milan (Italy).
AB - This paper deals with the connection which has been held on 8th July 1997 in
collaboration with the JPL of the NASA, Pasadena, California, between the Eighth
International Conference on the Advanced Robotics (ICAR '97) in course at
Monterey, California and the Telerobotics Laboratory of Politecnico di Milano
connected in a multipoint teleconference through the MCU of Rome with the Aula
Magna of the same Politecnico and the Palace Business of the Giureconsulti of the
Chamber of Commerce of Milan. The demonstration has allowed to telecontrol a
scara robot of the Sankyo and an ABB robot, which have affected simulations of
operations of biopsy to the prostate, to the liver and to the breast, a
mechanical hand and a model of a car, disposed in a space destined to reproduce
the Martian ground, from Monterey to Milan by means of the INTERNET+ISDN
connection from. In fact the event has taken place four days after the landing on
Mars happily successful of the spatial probe Pathfinder from which it has gone
out the "Sojourner" robot, telecontrolled from the JPL of the NASA, which has
begun to take photos of the Martian ground and also some of these images have
been transmitted in the course of the connection.
PMID- 10180592
TI - Virtual endoscopy software application on a PC.
PMID- 10180593
TI - Audio-guided blind biopsy needle placement.
AB - We discuss an implementation of an audio user interface for assisting surgical
placement tasks. We assembled and tested an apparatus for evaluating the
potential benefit of using audio guidance for assisting blind biopsy needle
placement tasks. This system improves upon an earlier system we demonstrated (see
[1]) by employing three dimensional audio processing as well as a facility for
algorithmically-motivated arbitrary waveform synthesis. Using this apparatus an
operator attempted to manually follow a predetermined biopsy needle insertion
path (trajectory) with an instrumented biopsy needle. This trajectory intercepted
a target object embedded within a custom biopsy phantom. The target was invisible
to the operator. Audio feedback provided the only means of trajectory and target
localization.
PMID- 10180594
TI - Telepresence interface with applications to microsurgery and surgical simulation.
AB - To address the needs for performing microsurgical procedures, the SRI
telepresence surgery workstation has been combined with a pair of
micromanipulator arms. The prototype microsurgery system has been tested with ex
vivo tasks similar to those required for surgical procedures, such as cutting,
grasping, suturing, and knot tying. Initial animal testing has been done on a rat
model in which end-to-end anastomosis of the femoral artery (approximately 1
millimeter in diameter) was completed with ten rats, and 100% patency was
obtained. To address the needs of surgical training, SRI has begun to develop a
system that uses a 6-DOF telepresence workstation. A computer-generated stereo
image is reflected in a mirror and appears to be superimposed on the surgeon's
hands, creating an immersive and realistic environment. Tools held in the
surgeon's hands are connected to left- and right-hand manipulators that both
continuously measure tool position/orientation and apply force/torque to the
tools. Furthermore, the visual image and tool locations are registered, so that
the user perceives that he or she is looking at and moving the simulated tools in
the visual image.
PMID- 10180595
TI - Reason and rationality in health and human services delivery.
PMID- 10180596
TI - Reason and rationality in health and human services delivery: an introduction.
PMID- 10180597
TI - The limits of scientific medicine: paradigm strain and social policy.
AB - In this essay, the historical roots of the dominant medical worldview will be
drawn and its tenets will be outlined. The existing paradigm may be called the
Western Biomedical Model, whose doctrines include body-mind dualism, physical
reductionism, the mechanical analogy, specific etiology and the body as the
appropriate focus of regimen and control. Some of the pressures straining the
paradigm will be discussed, especially the force of human and population aging
and the accompanying dominance of chronic illness as a focus of health care. The
tentative outlines of an emergent model will be described in the context of the
current health policy debate. The mind, biography, surrounding environment, and
culture are a few considerations that become very significant in a non-Cartesian
world.
PMID- 10180598
TI - Rationalizing decision-making through computer technology: a critical appraisal.
AB - As human services become more complex and multifaceted, sound decision-making
guiding the service delivery process becomes critical. Administrators and others
view computer technology as a means to rationalize the decision-making process at
all levels of organizational life. The Management Information System (MIS) and
program evaluations are viewed as technologies particularly useful for enhancing
the decision-making process through computer technology. The strengths and
limitations of computer technology are discussed. Strategies for using computer
technology responsibly are offered.
PMID- 10180599
TI - Sociomedical models and the epistemology of risk: the shortcomings of medical
decision-making research.
AB - Sociomedical decision-making models have provided the framework for understanding
individual choice regarding health risks and have had an enormous impact on the
practice of health education. Recently, some scholars have questioned the
usefulness of these models and have called for a new perspective. While some
newer decision-making models appear to be unique, it will be shown here that
these new approaches remain firmly grounded in value-expectancy tradition. By
examining sociomedical decision-making models with regard to their underlying
theory of human action and epistemological assumptions, the similarity of various
models will be exposed. The intent of this analysis is to illuminate the inherent
limitations of traditional medical decision-making models and to provide a
framework for developing a new approach.
PMID- 10180600
TI - Community-based epidemiology: community involvement in defining social risk.
AB - In traditional epidemiologic research, the concept of risk emerges from a
biomedical paradigm which draws heavily upon Cartesian-Newtonian ontological
assumptions. Rational assessment of individual risk is based on a culturally
conditioned metatheoretical framework that seeks specific causes for specific
disease conditions. This leads to the identification of "risk factors" that can
be individually modified. Research within this orientation tends to produce
interpretations of data which further condition and mold cultural understanding
of individual and social risks and the available choices that can be made to
modify these risks. Community-based eco-epidemiology balances reductionist
tendencies of individual risk-factor analysis against social context and local
knowledge gained through community involvement in the research process. The
community-based partnership model can contribute to a greater understanding of
the interrelatedness of social problems and individual risks on the part of
community participants and researchers alike.
PMID- 10180601
TI - A world view model of health care utilization: the impact of social and provider
context on health care decision-making.
AB - This article provides a conceptual model illustrating the filtering effect that
social factors have on a health care event. Individual, family and social network
filters translate the symptom for the patient before and after s/he enters the
health care delivery system. Simultaneously, managed care and provider filters
shape what resource is provided by the health care provider to the patient. Basic
premises are that decision-making about health care utilization is a complex
social interaction and that better attention to the social context will increase
the likelihood of effective health care occurring.
PMID- 10180602
TI - Health care policy in theory and practice: a review of the process as a product
of rational decision-making.
AB - Decisions are not made in a vacuum. Both theories and practical circumstances
influence how reason and decision-making are conceived. In this article, the
focus is on organizations and their impact on shaping the decision-making
process. Organizational theories, management philosophies, and structural
considerations are reviewed, with emphasis placed on how they influence the
search for information, the conceptualization of data, the possible uses of
knowledge, and the formation of behavioral goals. Accordingly, decision-making is
contextualized; organizational assumptions are linked to the reasonableness of a
decision. As modern writers say, the "taken-for-grantedness" of an organization
is illustrated to be tied inextricably to the nature of reason and assessments of
rationality.
PMID- 10180603
TI - Reason, the life-world, and health care delivery.
AB - Reason is illustrated to be conceived traditionally in an abstract manner. The
attempt has been made to make rationality appear value-neutral and universal. In
the end, however, this version of reason is ineffective, because the human
element is overlooked. Contemporary philosophy is shown to have abandoned this
ethereal view of knowledge and reason. Furthermore, interventions that are based
on this shift in theory are more socially sensitive and appropriate.
PMID- 10180604
TI - HCFA publishes interim final rule on PPS for skilled nursing facilities.
PMID- 10180605
TI - Proposed changes to hospital inpatient PPS include expanded definition of
transfers.
PMID- 10180606
TI - Taking the plunge: deciding to return to school.
PMID- 10180607
TI - Practice brief. Issue: writing an effective request for proposal (RFP). American
Health Information Management Association.
PMID- 10180608
TI - Education for life: K-80!
PMID- 10180609
TI - Developing personal effectiveness: practical tips to hone your skills.
AB - What is personal effectiveness, and how can qualities of leadership be developed?
Six AHIMA members (Leslie Fox, Barbara Fuller, Maida Herbst, Sandra Nunn, Brenda
Olson, and Gerri Smothers) were asked to comment. Here's advice from the experts
on how to perform effectively.
PMID- 10180610
TI - Education: the key to HIM transformation.
AB - Vision 2006 is pointing the way to the transformation of HIM practice. But
without individual action, the vision will not bear fruit. Education and
professional development are the keys to making the transition to HIM
professionals' roles and responsibilities in the next century.
PMID- 10180611
TI - Funding your education--an overview.
AB - Financial considerations are an important part of any decision to continue
education. Here's a guide to navigating the many financial aid options available
for postsecondary education.
PMID- 10180612
TI - Planning for the future of HIM practice: healthcare trends to watch.
AB - In a rapidly changing healthcare environment, HIM professionals are well advised
to stay abreast of industry trends. The author identifies 11 trends that are
likely to influence both the strategic and operational aspects of health
information management.
PMID- 10180613
TI - Multimedia: a new look at HIM classroom instruction.
PMID- 10180614
TI - What is Gulf War Syndrome? (Part I).
PMID- 10180615
TI - The status of graduate education programs in health information management.
PMID- 10180616
TI - Employees' perceptions of HIM students in clinical education.
PMID- 10180617
TI - Road runners. Getting supplies from here to there.
PMID- 10180618
TI - Patch work. Team stitches threadbare processes into a full-coverage operation.
PMID- 10180619
TI - Battling staff cuts? Cool heads win the day.
PMID- 10180620
TI - Don't let unions give you labor pains.
PMID- 10180621
TI - Make no small plans. Major redesign helps small hospital survive.
PMID- 10180623
TI - No more spores. New indicator aims to shake up sterilization monitoring.
PMID- 10180622
TI - Latex management a snap? Not by a long shot.
PMID- 10180624
TI - Case carts in the OR--size does matter.
PMID- 10180625
TI - Protecting patient data.
PMID- 10180626
TI - Use a streamlined approach for medical record abstraction.
PMID- 10180627
TI - NCQA, JCAHO, AMAP agree to coordinate but compete.
PMID- 10180628
TI - Hot spots for medication errors.
PMID- 10180629
TI - Managing data for quality improvement.
PMID- 10180630
TI - Memory.
PMID- 10180631
TI - A shot in the arm for an AIDS vaccine.
PMID- 10180632
TI - Taxation of employer-provided health coverage: inclusion, timing, and policy
issues.
PMID- 10180633
TI - Medicare Program; establishment of the Medicare+Choice Program--HCFA. Interim
final rule with comment period.
AB - The Balanced Budget Act of 1997 (BBA) establishes a new Medicare+Choice (M+C)
program that significantly expands the health care options available to Medicare
beneficiaries. Under this program, eligible individuals may elect to receive
Medicare benefits through enrollment in one of an array of private health plan
choices beyond the original Medicare program or the plans now available through
managed care organizations under section 1876 of the Social Security Act. Among
the alternatives that will be available to Medicare beneficiaries are M+C
coordinated care plans (including plans offered by health maintenance
organizations, preferred provider organizations, and provider-sponsored
organizations), M+C "MSA" plans, that is, a combination of a high deductible M+C
health insurance plan and a contribution to an M+C medical savings account (MSA),
and M+C private fee-for-service plans. The introduction of the M+C program will
have a profound effect on Medicare beneficiaries and on the health plans and
providers that furnish care. The new provisions of the Medicare statute, set
forth as Part C of title XVIII of the Social Security Act, address a wide range
of areas, including eligibility and enrollment, benefits and beneficiary
protections, quality assurance, participating providers, payments to M+C
organizations, premiums, appeals and grievances, and contracting rules. This
interim final rule explains and implements these provisions. In addition, we are
soliciting letters of intent from organizations that intend to offer M+C MSA
plans to Medicare beneficiaries and/or to serve as M+C MSA trustees.
PMID- 10180634
TI - Financial disclosure by clinical investigators; correction--FDA. Final rule;
correction.
AB - The Food and Drug Administration (FDA) is correcting a final rule that appeared
in the Federal Register of February 2, 1998 (63 FR 5233). The document issued
regulations requiring the sponsor of any drug, including a biological product, or
device marketing application (applicant), to submit certain information covering
the compensation to, and financial interests of, any clinical investigator
conducting certain clinical studies. The document was published with an error.
This document corrects that error.
PMID- 10180635
TI - Notice regarding section 602 of the Veterans Health Care Act of 1992--rebate
option--HRSA. Final notice.
AB - Section 602 of Pub. L. 102-585, the "Veterans Health Care Act of 1992", enacted
section 340B of the Public Health Service (PHS) Act, "Limitation on Prices of
Drugs Purchased by Covered Entities." Section 340B provides that a manufacturer
who sells covered outpatient drugs to eligible entities must sign a
pharmaceutical pricing agreement with the Secretary of HHS in which the
manufacturer agrees to charge a price for covered outpatient drugs that will not
exceed that amount determined under a statutory formula. The purpose of this
notice is to inform interested parties of the final guidelines recognizing a
rebate option for State AIDS Drug Assistance Programs (ADAPs) receiving funds
under Title XXVI of the PHS Act as an optional alternate means of accessing
section 340B discount pricing.
PMID- 10180636
TI - Health systems see mission and strategic gain in alternative therapies.
PMID- 10180637
TI - Hospitals taking on more risk and receiving less from commercial HMOs.
PMID- 10180638
TI - AHA advises emergency response review in wake of Chicago ER tragedy.
PMID- 10180640
TI - Are Georgia's hospitals prepared for the Year 2000?
PMID- 10180639
TI - More, not less, managed care may be the key to higher physician income.
PMID- 10180641
TI - Negotiated rulemaking progresses on HIPAA's risk-sharing exception.
PMID- 10180642
TI - Brace yourself for fallout from Medicare rate change.
PMID- 10180643
TI - Prepare now by learning the ABCs of PIP-DCGs (principal inpatient diagnostic cost
groups).
AB - The ABC of PIP-DCGs: How will HCFA's new Medicare payment system work? An expert
who developed the new pay rate based on hospital diagnoses explains what it is
and how it works.
PMID- 10180644
TI - Providers could emerge as winners in Medicaid--but follow these 6 strategies.
AB - Take the Medicaid plunge: Experts say the Medicaid market is ripe for entry by
providers thanks to recent legislative changes, new contracting trends, and an
exodus by HMOs. Here's an update on the market and important questions to ask
your potential plan partners before taking the plunge.
PMID- 10180645
TI - Expect variation in utilization, revenue based on plan affiliation, warns
Medicare risk provider.
AB - Anatomy of a Medicare risk contract: A seasoned California Medicare provider
shares the details on its risk contracts and warns other providers to expect wide
variation in performance based on plan affiliation. Here's the "inside story" on
how this provider has garnered 10% of the local market share, but it's sometimes
been an uphill struggle.
PMID- 10180646
TI - Survey finds states widen reach of Medicaid risk programs.
AB - Data File: What will industry trends mean for Medicaid providers? A new study
details industry changes in Medicaid risk and concludes that providers will see
new, more medically complicated and higher costing populations. Here are the
details and some interesting statistics--from types of covered populations to
marketing practices.
PMID- 10180647
TI - Increasing top management turnover: is it true and does it matter?
PMID- 10180648
TI - Development and testing of the UK SF-12 (short form health survey).
AB - OBJECTIVES: The 36 item short form health survey (SF-36) has proved to be of use
in a variety of settings where a short generic health measure of patient-assessed
outcome is required. This measure can provide an eight dimension profile of
health status, and two summary scores assessing physical function and mental well
being. The developers of the SF-36 in America have developed algorithms to yield
the two summary component scores in a questionnaire containing only one-third of
the original 36 items, the SF-12. This paper documents the construction of the UK
SF-12 summary measures from a large-scale dataset from the UK in which the SF-36,
together with other questions on health and lifestyles, was sent to randomly
selected members of the population. Using these data we attempt here to replicate
the findings of the SF-36 developers in the UK setting, and then to assess the
use of SF-12 summary scores in a variety of clinical conditions. METHODS: Factor
analytical methods were used to derive the weights used to construct the physical
and mental component scales from the SF-36. Regression methods were used to
weight the 12 items recommended by the developers to construct the SF-12 physical
and mental component scores. This analysis was undertaken on a large community
sample (n = 9332), and then the results of the SF-36 and SF-12 were compared
across diverse patient groups (Parkinson's disease, congestive heart failure,
sleep apnoea, benign prostatic hypertrophy). RESULTS: Factor analysis of the SF
36 produced a two factor solution. The factor loadings were used to weight the
physical component summary score (PCS-36) and mental component summary score (MCS
36). Results gained from the use of these measures were compared with results
gained from the PCS-12 and MCS-12, and were found to be highly correlated (PCS:
rho = 0.94, p < 0.001; MCS: rho = 0.96, p < 0.001), and produce remarkably
similar results, both in the community sample and across a variety of patient
groups. CONCLUSIONS: The SF-12 is able to produce the two summary scales
originally developed from the SF-36 with considerable accuracy and yet with far
less respondent burden. Consequently, the SF-12 may be an instrument of choice
where a short generic measure providing summary information on physical and
mental health status is required.
PMID- 10180649
TI - Comparing costs of monitoring glaucoma patients: hospital ophthalmologists versus
community optometrists.
AB - OBJECTIVES: To compare the costs of monitoring stable glaucoma patients by
community optometrists and hospital ophthalmologists. METHODS: A cost analysis
was conducted alongside a randomised controlled trial which compared the accuracy
and acceptability of measurement in each form of care. The viewpoints of the
health service and of patients were considered. Costs were assessed using a
number of different methods. Sensitivity analysis was conducted for key
variables. RESULTS: The baseline analysis reflected heavily the different length
of time between follow-up in the two arms of the trial (10 months (average) for
hospital, 6 months for optometrists). It showed annual cost per patient for
hospital ophthalmologists varied from 14.50 pounds to 59.95 pounds, and community
optometrist costs varied from 68.98 pounds to 108.98 pounds. Assuming a 6-month
follow-up interval for the hospital ophthalmologists, costs varied from 24.16
pounds to 99.92 pounds. CONCLUSIONS: Recommendations about the least costly form
of follow-up must depend on the context in which the decision is being taken and
the scale of change envisaged. If the aim is to recoup resources from hospitals
in order to pay for monitoring in the community, community monitoring is unlikely
to be the least costly option.
PMID- 10180650
TI - The iterative use of economic evaluation as part of the process of health
technology assessment.
AB - The economic evaluation of health care technologies has a key role within the new
National Health Service health technology assessment process. There has, however,
been little discussion of the best way of combining economic and clinical
research. Economic evaluation should be iterative, generating progressively
firmer estimates of cost-effectiveness and helping to maximise the efficiency of
health care R&D. Here, four stages of economic analysis are suggested, starting
with stage I when the basic clinical science is complete, and finishing with
stage IV analysis to generalise the results of earlier studies to routine
clinical practice.
PMID- 10180651
TI - Subjective and objective measures of health: which is better when?
PMID- 10180652
TI - Defining core services: New Zealand experiences.
AB - A key aspect of the New Zealand health reforms was the proposed development of an
explicit core of services to which all New Zealanders would have access. A range
of approaches has been taken by the government, its advisers, purchasers and
providers to describe sets of services to which New Zealanders are to have
access. The development of an explicit core aims to promote equity of access to
services, to ensure that those services available are those that are the most
cost-effective and the services New Zealanders feel to be the most important, and
to clarify entitlements to publicly funded health care. This paper describes the
current approaches that are being used to define core services in New Zealand,
discusses the reasons behind some of the choices made and notes some key issues
for further policy debate.
PMID- 10180653
TI - Advice-giving in community pharmacies in the UK.
AB - OBJECTIVES: To review (1) the published evidence on the information provided with
prescribed and purchased medicines by pharmacists and pharmacy assistants, (2)
clients' expectations of advice about medicines from community pharmacies and
their experience and use of it, and (3) appropriateness and rigour of study
methods used. METHODS: Papers, published between 1980 and 1995 inclusively, were
identified based on searches of on-line databases, a published literature index,
key pharmacy practice journals and cited references in the bibliographies of
published papers. Those papers selected reported research findings on any aspect
of medicines-related communications and the provision of advice about medicines
to members of the public who visited pharmacies in the UK. The comparatively
small volume of work and lack of design consistency meant that a subjective
assessment, rather than a criteria-based objective review, was deemed
appropriate. RESULTS: Forty-two suitable studies were identified and are
reviewed. No common definition of 'advice' has emerged. Most studies reported
were quantitative, concentrating on the frequency of advice-giving in community
pharmacies and only one study considered the impact of advice on outcome. The
quality of advice given was judged highly variable, although pharmacists'
referrals, where made, were considered appropriate. Given that pharmacy
assistants appear to make most of the medicine sales, remarkably few studies
addressed their contribution to advice-giving. The review can provide little
insight into what determines when advice is provided, but it does illuminate the
disparity between the advice that clients say they want and what they actually
seek. CONCLUSIONS: Where there appears to be a consensus that advice-giving in
community pharmacies is wanted, this review reveals a lack of shared
understanding between consumer bodies and the pharmacy profession about who needs
advice and when and how it should be given. The need for unsolicited advice
giving associated with the sale of medicines is particularly contentious. With
the current programme of deregulation of medicines, this is an increasingly
important issue to resolve. The authors suggest a need for a consensus-building
forum to generate guidelines that meet shared expectations between clients,
community pharmacists, government and the pharmaceutical industry.
PMID- 10180654
TI - Management for doctors.
PMID- 10180655
TI - Variation in guidelines.
PMID- 10180656
TI - Ivan Illich and the pursuit of health.
AB - Fifty years ago, when medicine had relatively few effective treatments to offer,
its value was unquestioned. Twenty-five years ago clinicians had become concerned
that treatment could sometimes do harm and McKeown published epidemiological
evidence claiming that medicine did little good. This state of affairs was used
by Illich to bolster his crusade against technology in general. Today it is clear
that medicine now makes a large contribution to health. But doubts still exist
and alternative pathways to health are continually exhorted. Large-scale efforts
at behavioural modification, encouraging the adoption of healthier lifestyles,
have been largely unsuccessful. Social activists now argue that funds should be
diverted from medical care to social programmes that, they claim, might
contribute more to health. While it is true that health is strongly associated
with socio-economic status (income, education and occupation), there is little
sense of how best to reallocate scarce resources so as to improve the health
impact of social and economic programmes. Social reform is not a substitute for
medical care. Rather, our social environment is a second, important but quite
separate, determinant of health and well-being.
PMID- 10180657
TI - Factors influencing the attendance rate at accident and emergency departments in
East London: the contributions of practice organization, population
characteristics and distance.
AB - OBJECTIVES: To examine the contribution of general practice organisation,
population characteristics and distance to practice attendance rates at four
local accident and emergency departments. DESIGN: Practice-based study examining
variations in accident and emergency department attendance rates in 105
practices, using routine data from the Family Health Services Authority (FHSA),
the District Health Authority and the 1991 Census. SETTING: East London and the
City Health Authority, covering practices based in the inner city boroughs of
Hackney, Tower Hamlets and Newham, and the City of London. MAIN OUTCOME MEASURE:
Practice-based, age-standardized, adult attendance rates at accident and
emergency departments in the year to 31 March 1994. RESULTS: Annual age
standardized practice accident and emergency department attendance rates ranged
from 10.3 to 29.4 per 100 population. The mean practice attendance rate was 17.6
per 100 (95% CI 16.8-18.4). No significant relationship was found between
attendance rates and practice characteristics (number and sex of general
practitioner (GP) principals, presence of practice manager or nurse,
computerization and training status). There were strong positive relationships
between attendance rates and households not owner-occupied (R = 0.55, P < 0.001)
and pensioners living alone (R = 0.55, P < 0.001). There were negative
correlations with Asian ethnicity (R = -0.31, P = 0.002) and residents lacking
amenities (R = -0.26, P = 0.007). The distance to the nearest accident and
emergency department also correlated negatively with attendance (R = -0.27, P =
0.006). A backwards multiple regression model showed that 48% of the variation in
attendance rates could be accounted for by six factors: percentage of households
not owner occupied, percentage living in households without a car, percentage
living in households lacking amenities, percentage of pensioners living alone,
percentage of Asian ethnicity, and percentage living in households with a head
born in the New Commonwealth and Pakistan. Optimal subsets regression identified
a number of alternative models with similar explanatory value. CONCLUSIONS:
Social deprivation is strongly linked with attendance rates at accident and
emergency departments in East London. In contrast, the organizational
characteristics of general practices appear to have no bearing on the rates. Both
purchasers and providers need to take account of these findings when planning
accident and emergency provision.
PMID- 10180658
TI - Evaluating interventions to promote patient involvement in decision-making: by
what criteria should effectiveness be judged?
AB - Interventions to inform patients about health care options and to involve them in
decisions about their care are now widely advocated. The question of which
criteria should be used to judge the effectiveness of such interventions has,
however, received little attention. The provision of research-based information
about health care effectiveness to patients and the promotion of greater patient
involvement in health care decision-making are likely to have a complex range of
effects on: the information provided to patients; patients' acquisition of
skills; patients' knowledge and emotions; how decisions are made; the quality of
decisions; professional-patient relationships; the use of health care; the health
of patients; satisfaction; and the organisation and cost of health services.
Opinions about which effects are most important and how they should be measured
and valued will be influenced by a variety of factors, including: the rationales
and motives underlying interest in patient involvement in decision-making; the
forms of patient involvement envisaged; and the types of interventions being
considered. In the context of health care systems which aim primarily to improve
health status and well-being, health outcomes should take priority over process
variables such as decision-making behaviours and patients' knowledge.
PMID- 10180659
TI - Extrapolation of cost-effectiveness information to local settings.
AB - Providers and purchasers of health care are increasingly looking to the results
of economic evaluations for guidance when making their decisions. In this paper
the authors argue that there are dangers involved in the naive and unthinking use
of published cost-effectiveness information outside the setting in which the
information was generated. In considering whether the results of a published
study are likely to be relevant locally, decision-makers are encouraged to assess
whether the values of the key parameters reported in the published study apply
locally. The possible sources of variation are described: unit cost differences;
differences in the prevalence, incidence or natural history of disease; and
differences in the comparators. In situations where the only source of variation
is that local unit costs are different, local values can be substituted in the
published analysis and local cost-effectiveness results estimated. Where the
other sources of variation exist, the decision-maker is required to make an
assumption about the nature of the interaction between the sources of variation
and the values of the cost-effectiveness parameters. Using an example, the
authors argue that local threshold analysis can aid decision-making where the
policy change being considered has a high probability either of increasing
effectiveness or reducing costs. Without local re-analysis, there is a danger
that local policy changes in line with the recommendations of published studies
will promote inefficiency. Re-analysis in the local setting is, however, reliant
on authors of economic evaluations being explicit about their methods and the
comparators used in their analyses.
PMID- 10180660
TI - Pay in the British NHS: a local solution for a national service?
AB - An important component of the reforms of the British National Health Service
(NHS) has been devolution of a previously highly centralised pay bargaining
system to the local provider level. As the wage bill is by far the single largest
item of health care expenditure, the implications of this change may be far
reaching. This article surveys the available theory and evidence from an economic
perspective. It reviews the development of pay determination mechanisms in the
NHS and the extent to which local pay has been adopted since the reforms were
introduced. It then considers the theory of local pay and general evidence on
local pay variations in the UK, before turning to the available evidence on local
labour markets in the health care sectors of the UK and USA. It concludes with a
discussion of the policy and research implications of current developments on
local pay bargaining in the NHS. In particular, it suggests that judgements over
the success or failure of local pay bargaining will concern: first, whether the
weakened monopsony position of the NHS at national level results in higher pay
for the more powerful employee groups; second, whether fragmentation of
bargaining weakens the negotiating and lobbying power of national trade unions
and professional organisations; third, whether competition between providers
leads to higher or lower costs; and fourth, whether any efficiency gains from
local bargaining outweight the higher transaction costs involved.
PMID- 10180661
TI - Concepts of rigour and implications for health services research.
PMID- 10180662
TI - Informed consent: ideal or reality?
AB - Is it ever possible to give informed consent to treatment or research? Are the
standards of consent set by ethicists and lawyers too high for ordinary people to
reach? Should these standards be abandoned or modified? These questions are
discussed in this paper mainly in relation to the extensive literature on consent
in medicine, with examples about consent to children's treatment and research
which raise extra dilemmas. Paradoxical meanings are considered: consent as an
informed correct choice or a courageous best guess, and autonomy as isolated,
uncompromised freedom or reasonably uncoerced self-realisation. Beyond being
informed, consent involves evaluating, making and signifying a decision. It is
better understood as a process than an event, in which reasoned understandings
can be complemented by emotional insights. Ethical and legal standards of
voluntary consent, although partly an unrealistic ideal, provide important
guidelines for people who request and give consent to research.
PMID- 10180663
TI - The Amsterdam Treaty and the future of European health services.
PMID- 10180664
TI - Measuring hospital outcomes: don't make perfect the enemy of good!
PMID- 10180665
TI - Establishing patient preferences for blood transfusion support: an application of
conjoint analysis.
AB - OBJECTIVE: To develop a method of determining the relative importance of waiting
time and location of care for patients with haematological disorders requiring
red cell transfusion. Such information is particularly relevant when evaluating
interventions that affect patient well-being (e.g. by changing waiting time and
location) but do not affect health outcomes. METHODS: Conjoint analysis is used
to assess the relative importance of waiting time and location with respect to
pre-transfusion testing and red cell transfusion. Compensation is also included
as an attribute in order to estimate the monetary value of changes in waiting
time and location. RESULTS: Waiting time and location are important attributes in
the provision of pre-transfusion testing and red cell transfusion. Compensation
is not an important attribute. On average patients are willing to wait an
additional 45 minutes in order to have pre-transfusion testing in their own home
and an additional 35 minutes in order to receive red cell transfusions in their
preferred location. CONCLUSION: The relative importance of waiting time and
location of care was established. However, it was not possible to assign monetary
values since compensation was not an important attribute for these respondents.
The paper highlights the scope for using conjoint analysis to analyse the non
health benefits that may result from changes in the delivery of care.
PMID- 10180666
TI - Health policy in transition: terminal care and site of death in Japan.
AB - OBJECTIVES: In Japan, hospitals have replaced homes as the predominant site of
death, especially for the elderly. Site of death is a reliable indicator of where
older people receive care before they die. We conducted a population-based study
to identify the factors that determine site of death in a typical rural area in
Japan. METHODS: Study subjects were residents of Kawakami town, aged 70 years or
older, who died during 1981 and 1990. Death certificates provided information on
age, gender, cause of death, duration of illness before death, family members,
family occupation, and site of death. RESULTS: Among 455 subjects, 52.7% died at
home, while 47.3% died in hospital. Multiple logistic regression analyses
indicated that subjects with cancer were 6.1 times more likely to die in
hospitals than those with other diseases. Subjects who died in their seventies
were 2.3 times more likely to die in hospital than older subjects. Members of non
farming families were 1.7 times more likely to die in hospital than members of
farming families. Gender, duration of illness, and the presence of spouse or
children in the household were not significantly related to site of death
according to multivariate analyses, although trends did exist. CONCLUSION: This
case study illustrates the importance of developing geriatric care systems in
Japan, utilizing alternatives to hospitals, such as nursing homes and formal home
care. This is particularly true for patients with cancer. As the older population
rapidly increases in Japan, the need for alternatives in geriatric care grows
more critical.
PMID- 10180668
TI - The SF-36 physical and mental health summary measures: an example of how to
interpret scores.
AB - OBJECTIVES: To provide normative data, in the form of percentile scores from a
community sample, for the Physical Component and Mental Health Component Summary
scores derived from the SF-36, and to provide an example of how to interpret
scores on these measures, comparing normative results with data from a clinical
sample. METHOD: Normative data were gained from a postal survey using a
questionnaire, containing the SF-36 and a number of other items concerned with
lifestyles and illness. The questionnaire was sent to 13,042 randomly selected
subjects between the ages of 18 and 64 years, drawn from Family Health Services
Authority computerised registers for four English counties. The clinical sample
comprised 84 patients aged 18-64 years diagnosed with obstructive sleep apnoea
(OSA) who were asked to take part in the study. The Physical Component Summary
(PCS) score and Mental Health Component Summary (MCS) score gained from the SF-36
health status measure were the outcome measures. RESULTS: The community survey
achieved a response rate of 72% (n = 9332). All 84 patients in the age range 18
64 years approached to take part in the OSA study agreed to do so; complete data
were available for 60 patients. Results indicated that, prior to treatment, 75%
of OSA patients' scores on the PCS/MCS were less than the standardised mean score
of 50 and fell in the lowest 34% of scores in the general population. However,
after treatment, over 50% of patients scored above the standardised mean score on
both the PCS and MCS and more closely mirrored the distribution of the normative
sample. CONCLUSION: The data provided here should enable a more meaningful
presentation of data than is generally provided in research papers presenting SF
36 summary scores.
PMID- 10180667
TI - Determinants of ambulatory physician utilization among adults with chronic
diseases in Quebec.
AB - OBJECTIVES: To test the explanatory power of a model of ambulatory service use
and to determine the relative roles of the main determinants of physician
utilization for two chronic medical conditions in adults in Quebec. METHODS: A
behavioral model based on Andersen's model was developed and tested by linking
two databases: the Quebec health survey as regards patient characteristics, and
the Quebec health insurance board data on physician characteristics and service
use. Path analysis was used for data analysis. RESULTS: The model explained a
little less than 20% of the variation in service use. The number of
hospitalizations, physician's specialty and perceived health were the most
important predictors of the volume of visits. CONCLUSION: Further specification
of utilization, relating it to a particular medical condition, does not
necessarily lead to an increase in the explanatory power of the model. We
recommend that future research should put more emphasis on provider-related
determinants rather than focusing on the type and purpose of utilization.
PMID- 10180669
TI - Advice giving in community pharmacies: a response concerning methods for future
research.
PMID- 10180670
TI - Error reporting does a turnaround.
PMID- 10180671
TI - Automation doesn't mean an end to errors.
PMID- 10180672
TI - Dick Tracy device averts a myriad of errors.
PMID- 10180673
TI - Look at 'whole universe' under new reimbursement rules.
PMID- 10180674
TI - ED controversy triggers policy changes.
PMID- 10180675
TI - Failed barriers cause human errors.
PMID- 10180676
TI - Economic transition and health transition: comparing China and Russia.
AB - Drawing on experiences from China and Russia (the world's two largest
transitional economies), this paper empirically examines the impact of economic
reforms on health status. While China's overall health status continued to
improve after the economic reform, Russia experienced a serious deterioration in
its population health. The observed differences in health performance between
China and Russia can be explained by the different impacts of economic reforms on
three major socioeconomic determinants of health. Depending on whether or not the
reform improves physical environment (as reflected in income level and
nutritional status), social environment (including social stability and security
system), and health care, we would observe either a positive or a negative net
effect on health. Despite remarkable differences in overall health development,
China and Russia share some common problems. Mental and social health problems
such as suicides and alcohol poisoning have been on the rise in both countries.
These problems were much more serious in Russia, where political and social
instability was more pronounced, associated with Russia's relatively radical
reform process. With their economies moving toward a free market system, health
sectors in China and Russia are undergoing marketization, which has had serious
detrimental effect on the public health services.
PMID- 10180677
TI - Effects of user charges on the use of prescription medicines in different socio
economic groups.
AB - This study examined the sensitivity towards increases in user charges for
different types of drugs and among different socio-economic groups. It was based
on responses by 2008 consumers of prescription drugs to a self-administered
postal questionnaire sent to a random sample of 8000 inhabitants in Uppsala
County in Sweden. The questionnaire included a question about whether the
respondents would use fewer prescription drugs if the user charges increased by a
specific amount. The increase in user charges was varied between 9 and 150% in
five different subsamples. Logistic regression analysis was used to estimate the
probability that a respondent would reduce consumption of prescription drugs as a
function of the size of the user charges increase, socio-economic characteristics
and the type of drug used. Results showed that the price sensitivity decreased
with increasing age, income, education and self-rated health status. Price
sensitivity was highest for antitussives and lowest for climacteric drugs. If the
user charges doubled, 40% of antitussives users would reduce their consumption
whereas only 11% of climacteric drugs users would reduce their consumption. It is
concluded that sensitivity to increases in user charges varied greatly between
different types of drugs and between socio-economic groups. The young, those with
poor health status, low education and low income are most likely to decrease
consumption of prescription drugs when user charges increase.
PMID- 10180678
TI - The meaning of urgency in the allocation of scarce health care resources; a
comparison between renal transplantation and psychogeriatric nursing home care.
AB - In the juridical and ethical literature on patient selection criteria it is an
unargued premise that those who are most urgently in need of treatment or care
will be given priority. The aim of this study is to gain insight into the medical
practice of waiting list problems and patient selection at the microlevel,
especially with respect to urgency. Thus, the study intends to contribute to the
medical ethical discussion on patient selection for scarce resources. The results
of qualitative research into the meaning and occurrence of urgency in two health
care services, renal transplantation and psychogeriatric nursing home care, are
discussed. In the first sector, patients are seldom considered urgent. Criteria
for urgency are technical dialysis problems or severe psychological burden due to
protracted dialysis treatment. In contrast, psychogeriatric patients are often
considered urgent, with the principal criterion being too heavy a care load for
informal carers. Both health care services show variation in assigning urgency
codes. It appears that the exact meaning of urgency is not self-evident and that
admission of urgent patients to nursing homes can be negotiated by professionals
or informal carers. This points to the necessity of a discussion within these
services as to the actual content matter of urgency. Further, professionals
involved in renal transplantation raise several moral and practical arguments
against giving patients priority, even if they need treatment urgently. It shows
that distributive justice cannot always be applied. Occasionally non-urgent
patients are rated urgent as they have been waiting very long due to specific
allocation procedures. In these cases urgency is granted in an unexpected way
that is ultimately in accordance with the notion of procedural justice.
PMID- 10180679
TI - Primary care reform: a three country comparison of 'budget holding'.
AB - Governments in most developed nations have been looking to organisational and
financial reform of health systems over the last decade. Although the structure
and problems of the health care sector in each country may differ, with countries
correspondingly adopting different reform agendas, there has been some element of
commonality in reforms: that of (managed) competition. Of particular importance
in such reforms has been the strengthening of primary care. General practitioners
and primary care physicians, as 'gatekeepers' to the health system, are
increasingly being called upon to be accountable; not only for their patients'
health but also for the wider resource implications of any treatments prescribed.
In some countries this role has been formalised through establishing 'budget
holding' for general practitioners and primary care physicians, for example,
through general practice 'fund holding' in the UK, Health Maintenance
Organisations in the USA, and Independent Practice Associations in New Zealand.
This paper examines: (i) what such budget holding seeks to achieve; (ii) the
effectiveness of the budget holding experience to date in achieving these
objectives; and (iii) factors which appear to determine the success of budget
holding in achieving its objectives.
PMID- 10180681
TI - Health policy and the information highway.
PMID- 10180680
TI - Market--what market? A review of Health Authority purchasing in the NHS internal
market.
AB - This paper argues that the British NHS Reforms (the 'Reforms') set out in Working
for Patients [1] largely failed to create a market, to achieve the changes that
market forces might have been expected to achieve or to meet the objectives set
for the NHS in Working for Patients. It draws on the available literature and the
author's experience of work with the NHS during the 6 years after Working for
Patients. It is hampered, as are all such reviews of the UK Reforms, by the lack
of a detailed and systematic research appraisal of the internal market. Many
small changes, resulting from market mechanisms, may have occurred throughout the
NHS without being publicized or well documented. But overall, there is little
convincing evidence that the Reforms have achieved their goals or met the
objectives of the politicians who initiated them. The argument here is
necessarily limited by the space available (but see [2] for a detailed analysis
of the NHS Reforms). The initial sections of the paper examine the
characteristics of markets and market power and the extent to which the NHS
Reforms created a market, with health authorities and fund-holders as its buyers.
The paper concentrates in particular on health authorities. Later sections then
examine the extent to which the Reforms met the objectives set out in Working for
Patients.
PMID- 10180682
TI - Managing patient length of stay better using an appropriateness tool.
AB - A multidisciplinary group from two medical floors at the Royal Victoria Hospital
chose the Managed Care Appropriateness Program (MCAP) to evaluate the
appropriateness of the days of stay for their patients. Of 100 charts of
consecutive patients examined by the nurse reviewer (comprising 1,095 patient
days), 33 percent of the days were deemed inappropriate. The reasons for each of
these inappropriate days were documented, and strategies were implemented to
address the issues. The major outcome of the study was a change in the culture of
the health professionals to a more positive approach to defining and carrying out
efficient patient care.
PMID- 10180683
TI - Managing change in the context of health reform: lessons from Alberta.
AB - A qualitative field study of health system reform in Alberta was undertaken to
identify, describe, compare and contrast the processes of change management
adopted and implemented as a result of legislated health policy shift. Chairs and
chief executives of the new regional health authorities and provincial leaders
managing the change processes within Alberta's health care system were
interviewed. Components of change strategies important to the structure, process
and impact of the health policy shift to a regionalized system of care were
identified and analyzed. Stakeholders involved in managing change inside
Alberta's health care system were able to consistently identify a range of issues
important to beginning and sustaining health policy shift. These issues and
insights did not come from the literature, but rather from experience. To test
and share this experience further, it will be important to study more consciously
the management of change in relation to expected outcomes. With so many natural
experiments altering health care systems across Canada and beyond, a window of
opportunity exists for researching both the quality and quantity of such change,
comparing and sharing findings over time and, eventually, linking process to
outcome.
PMID- 10180684
TI - Evaluating an alternative funding plan.
AB - There have been increasing levels of interest shown across Canada in the
potential application of alternative funding arrangements for academic health
science centres. This article outlines the approach, and some preliminary
results, of the alternative funding plan evaluation at Queen's University.
Following a discussion of the AFP itself, the article describes the first phase
of the evaluation process. Several studies nearing completion are outlined, as
are other pieces of research that will be conducted before the AFP is
renegotiated in 1999. Finally, the authors provide a brief discussion of the
organizational and methodological issues that emerge when evaluating an AFP.
PMID- 10180685
TI - Surviving change: one district health board's experience.
AB - This qualitative evaluation examines critical steps the Moose Jaw-Thunder Creek
District Health Board initiated to address health reform; in particular, the
adoption of a governance philosophy, restructuring of services, development of a
comprehensive planning process, and implementation of a communication strategy.
The outcome has been a yearly health plan that maintains quality health services;
provides opportunities for service growth, client-centred health delivery and
increased accountability through defined outcomes; and ensures that the Board
ends the year with a balanced budget.
PMID- 10180686
TI - How to move things around a hospital: transport logistics at St. Michael's.
AB - Ongoing fiscal restraint challenges hospitals to focus their resources primarily
on core services. Support services receive much less attention. This article
describes the experience of Toronto's St. Michael's Hospital when it re
engineered its transport logistics by consolidating centralized support services
into a logistics department and creating new roles and processes to enhance
patient care.
PMID- 10180687
TI - Executive interviewing: maximize your impact.
PMID- 10180688
TI - A third path for health care.
PMID- 10180689
TI - Functioning as a unified whole for the patients' sake. Interview by Matthew D.
Pavelich.
PMID- 10180690
TI - Do Good Samaritan laws cover in-hospital emergencies?
PMID- 10180691
TI - Strength in numbers: could doctor unions really be the answer?
PMID- 10180692
TI - Group practices. They keep adding to their menu of services.
PMID- 10180693
TI - How a practice merger can give you a better retirement plan.
PMID- 10180694
TI - "I'd rather be a doctor than a congressman.".
PMID- 10180695
TI - What an ace administrator can do for a group.
PMID- 10180696
TI - Accrual accounting: easy as 1,2,3.
PMID- 10180697
TI - Providers bundle charges under consolidated billing.
PMID- 10180698
TI - A view from the top.
PMID- 10180699
TI - Watching for investor reactions.
PMID- 10180700
TI - RUGs: a new bridge to payment.
PMID- 10180701
TI - Putting costs under a magnifying glass.
PMID- 10180702
TI - Getting staff in sync with PPS.
PMID- 10180703
TI - PPS weighs in with legal concerns.
PMID- 10180704
TI - Providers as grass-roots lobbyists.
PMID- 10180705
TI - The quest for integration.
PMID- 10180706
TI - Millennium problem threatens health care billing systems. Providers need to get
ready.
PMID- 10180707
TI - Group decisions. Network members must decide on a management structure that will
meet each partner's needs.
PMID- 10180708
TI - When a guarantee is not a crime. Admission to nursing facilities cannot be
dependent on third-party payment guarantees.
PMID- 10180709
TI - Staff for stroke rehabilitation.
PMID- 10180710
TI - Keep residents smiling. Adaptive devices can help maintain oral health.
PMID- 10180711
TI - Help wanted. Employers are finding that the Internet can be a valuable
recruitment resource.
PMID- 10180712
TI - Test your financial IQ.
PMID- 10180713
TI - Take a deep, cleansing breath--and feel 21st century medicine.
PMID- 10180714
TI - An act of faith. Parish nursing treats the mind, body, and spirit.
PMID- 10180715
TI - Good neighbors make good health.
PMID- 10180716
TI - The top ten trends in managed care.
PMID- 10180717
TI - Care for the poor: the worst is yet to come.
PMID- 10180719
TI - Towards meaningful laboratory tests for evaluation of pharmaceutical aerosols.
PMID- 10180718
TI - Comparability of albuterol delivered by a piezoelectric device versus metered
dose inhaler in patients with chronic obstructive airways disease.
AB - In recent years, there has been increased interest in developing propellant-free
inhalers for the treatment of patients with chronic obstructive airways disease.
Various powder inhalators have been developed. A recent alternative to the dose
metered aerosols has been produced using the piezoelectric effect. This double
blind, double-dummy, randomized, dual-dose, four-period crossover study was
designed to compare the effect of albuterol inhaled from the piezoelectric device
(PED) and albuterol inhaled from the metered dose inhaler (MDI). The primary
efficacy variables were forced expiratory volume in one second (FEV1) and area
under the curve (AUC). Although we found a statistically significant device
effect for the primary efficacy variables, the two treatments (PED [test] and MDI
[reference]) are comparable. The only variable for which comparability was not
found was time of onset. We found no dose differences. In conclusion, we found a
similar effect of albuterol inhaled by a PED versus an MDI in patients with
chronic obstructive airways disease.
PMID- 10180720
TI - Respirable mass: vague and indefinable in disease.
PMID- 10180721
TI - United States Pharmacopeia recommendations for the testing of inhalers.
PMID- 10180722
TI - Impact of oropharyngeal deposition on inhaled dose.
PMID- 10180723
TI - Mouth and oropharyngeal deposition of pharmaceutical aerosols.
PMID- 10180724
TI - The current laboratory determination of "respirable mass" is not clinically
relevant.
PMID- 10180725
TI - The revision of the Inhalanda monograph of the European Pharmacopoeia.
PMID- 10180726
TI - New concept for the variable flow rate Andersen cascade impactor and calibration
data.
PMID- 10180727
TI - The role of inertial particle collectors in evaluating pharmaceutical aerosol
delivery systems.
AB - Design theory for cascade impactors is well developed, and design principles can
be summarized quite succinctly. The key geometric parameters of three commonly
used impactors have been compared to design guidelines. Calibration theory and
practice have undergone improvement in recent years. Published results show
distinctly different characteristics for three commonly used impactors, and
conformance to modern design recommendations results in desirable performance
characteristics. A consideration of the sensitivity of stage collection
efficiency characteristics to geometric variables and flow rate indicates that
measurement of certain physical dimensions is sufficient to assure that impactor
performance matches that of a properly calibrated unit. Flow rate is an important
operating variable that is more likely to fall out of its calibrated range than
important dimensional variables resulting from instrument manufacturing. In
practice, data from impactors are frequently treated as though the impactors have
ideal collection characteristics. The practical effects of impactor nonideal
performance can be demonstrated by model calculations, and these show the
necessity of data inversion to obtain a size distribution. The process is not
straightforward for unknown distributions. There are much smaller differences
between ideal and real performance for an impactor complying with design
guidelines, thus, the cutoff characteristics are sharp.
PMID- 10180729
TI - Metered dose inhaler aerosol deposition in a model of the human respiratory
system and a comparison with clinical deposition studies.
PMID- 10180728
TI - Combined dose uniformity and particle size testing: the Canadian experience.
PMID- 10180730
TI - Relevance of radiolabeled steroid inhalation studies to clinical outcomes.
PMID- 10180731
TI - Predicting in vivo lung deposition of cromolyn sodium from in vitro estimates.
PMID- 10180732
TI - Can in vitro particle size measurements be used to predict pulmonary deposition
of aerosol from inhalers?
PMID- 10180733
TI - Strategy for the in vitro testing of spacers and holding chambers that may be
used with young children.
PMID- 10180734
TI - Discrepancy between in vitro and in vivo dose variability for a pressurized
metered dose inhaler and a dry powder inhaler.
PMID- 10180735
TI - Comparisons between inhaled fine particle fractions and lung dose for nebulized
aerosols.
PMID- 10180736
TI - A review of issues relating to nebulizer standards.
AB - The standardization of in vitro bench-top assessment of nebulizer performance
could prove to be extremely beneficial in the advancement of aerosol delivered by
nebulizers. At the present time, there is considerable confusion as to how
different nebulizer systems perform. Clinical in vivo tests are often
compromised, as high patient variability requires large study numbers before
differences become significant. In vitro tests should offer less variability and
much lower costs, but the test criteria must be standardized and be clinically
representative. Standard methods to assess nebulizer performance should therefore
be designed to reflect the clinical situation as far as practicable. This would
incorporate test methods involving: 1. simulated breathing patterns to estimate
the amount of aerosol released and inhaled 2. use of solute tracers to measure
aerosol release of salts or drugs themselves 3. use of aerosol sizing instruments
such as low-flow cascade impactors that would reflect in vivo deposition.
Standards must be written to accommodate the variety of existing devices
currently on the market. Because standards take a significant time (typically 1-3
years) to prepare and are intended to operate for a further 10 or more years,
they should also aim to accommodate possible advancements in device technology.
The potential for such developments should not be overlooked in preparing a
standard for in vitro testing of nebulization devices.
PMID- 10180737
TI - Errors in characterizing nebulized particle size distributions with cascade
impactors.
PMID- 10180738
TI - Design and testing of aerosol delivery systems for reproducible clinical
performance.
PMID- 10180739
TI - What is a respirable dose?
PMID- 10180740
TI - In vitro testing of aerosols: what does the future hold?
PMID- 10180741
TI - How well do in vitro particle size measurements predict drug delivery in vivo?
PMID- 10180742
TI - Determining permeability and diffusion rates in polymer films and packaging
materials.
AB - This article describes a rapid and effective means of calculating diffusion and
permeability constants for a range of polymer films and packaging materials with
various vapours. The sealed diffusion-cell method, in combination with a high
performance DVS-1 gravimetric analysis system, provides fundamental data for thin
films and rapid screening of composite films when designing advanced packaging
systems or calculating potential shelf-life of packaged devices.
PMID- 10180743
TI - Detecting sterilization effects on packaging.
AB - There must be evidence to show that medical devices and their packaging are
compatible with the sterilization process that is used. Here, results from
analysis of some medical-grade polystyrene packaging highlight the benefits
offered by current surface analysis techniques.
PMID- 10180744
TI - Implementation of the Medical Device Directive in Italy.
AB - The implementation of the European medical devices Directives by Member States is
introducing a significant regulatory uniformity to the European regulation of
medical devices. However, Member States are not required to implement the
Directives in an identical manner. As a result, it is important to be aware of
national variations. This article will discuss the implementation of the Medical
Device Directive in Italy.
PMID- 10180745
TI - Spreading the message: the significance of CE-marking.
AB - Considerable time and resources have been invested in developing the Medical
Device Directive. This article outlines some initiatives to publicize the meaning
and importance of the CE mark to clinicians, users and patients, which have been
developed by the United Kingdom Medical Devices Agency and industry.
PMID- 10180746
TI - From leaking devices to smart permeability: the technology of diffusion and other
transport mechanisms.
AB - Some devices are required to be totally leak-proof, others are specifically
designed to control permeability of one component through another. Some of the
principles of diffusion and some of the practical applications are discussed in
this article.
PMID- 10180747
TI - Reassessing the relevance of pharmacoeconomic analyses in formulary decisions.
PMID- 10180748
TI - The use of the bootstrap statistical method for the pharmacoeconomic cost
analysis of skewed data.
AB - In pharmacoeconomics, the comparison of the costs of 2 different drugs used for
the same treatment is of great interest. The problem is especially challenging
when the drugs are likely to produce costly adverse effects in a small number of
patients, which is often the case. The data are then skewed and traditional
statistical methods to analyse the difference in the mean costs produced by 2
treatments may be inappropriate. The bootstrap method is presented as an
alternative approach. A pharmacoeconomic cost-analysis example is presented and
used throughout this article.
PMID- 10180749
TI - Should antibacterials be deregulated?
AB - Deregulation of antibacterials is a recurrent topic in the debate on
pharmaceutical policy. This article focuses on one aspect of pharmaceutical
regulation, namely the requirement of a medical prescription for purchasing
antibacterials. However, a strategy of deregulation should not only concern the
switch from prescription-only status to nonprescription status for a given drug,
but should consider some complementary measures to minimise potentially harmful
effects on health and costs. Risk-benefit and economic evaluations, which are
possible approaches to assess the convenience of antibacterial deregulation,
force the empirical evidence, the assumptions, as well as the value judgements on
which the options are evaluated, to be made explicit. We outline the basic traits
of an economic-evaluation approach to assess the issues related to the public
interest and the feasibility of a deregulation policy. However, the answer cannot
be a generic one, but should address the question for each particular country,
and for each antibacterial and indication. Given the limitations of existing
evidence on that issue, a tentative research agenda is also proposed.
PMID- 10180751
TI - Predicting hospitalisation of patients with diabetes mellitus. An application of
the Bayesian discriminant analysis.
AB - The objective of this study was to develop, and subsequently test, a Bayesian
discrimination model for the purpose of identifying both the personal and the
healthcare system characteristics predictive of hospitalisation for the treatment
of patients with diabetes mellitus or commonly observed cormorbidities associated
with the disease. First, a Bayesian classification framework was proposed. The
model was then tested by using a logit regression technique in order to estimate
the probability of one or more hospitalisation events among patients with
diabetes. The study used claims data extracted from the Hawaii Medical Service
Association (HMSA) Private Business Claims (PBS) files for the 1995 calendar
year. Patients under 65 years were identified by paid claims with ICD-9-CM
diagnosis codes of 250.xx which gave a sample size of 6841 patients. Age, gender,
various pharmacotherapy variables, presence of hypertension, hyperlipidaemia,
congestive heart failure, multiple cardiovascular diseases, any combination of
commonly observed comorbidities, dialysis services and annual eye examination are
highly predictive of 1 or more hospitalisation events. The model shows a
predictive power of almost 90%. This study found that multivariate discriminant
analysis using a logit regression model successfully identifies: (i) important
explanatory variables predictive of hospitalisation; (ii) assigns patients into 1
of 2 mutually exclusive classes; and (iii) offers a benchmark for a comprehensive
disease management strategy for patients with more complicated diabetes.
PMID- 10180750
TI - Economic analysis of fluconazole versus amphotericin B for the treatment of
candidemia in non-neutropenic patients.
AB - Fluconazole (FLU) is an alternative to amphotericin B (AMB) for the treatment of
candidemia in non-neutropenic patients. This agent has similar clinical efficacy
but significantly reduced adverse effects compared with AMB. Using the database
from a Canadian randomised multicentre comparative trial of FLU versus AMB in the
treatment of non-neutropenic patients with candidemia, an economic analysis of
antifungal therapy was conducted from a Canadian hospital perspective. Patient
records were examined for information containing hospital resource consumption.
This included the costs for primary intravenous therapy with either AMB or FLU,
laboratory tests, patient clinical monitoring and adverse effects management. The
robustness of the baseline results were then tested by a comprehensive
sensitivity analysis. The mean duration of therapy in the AMB and FLU arms was
17.1 and 23.7 days, respectively (p < 0.001). Assuming that all of the FLU was
administered intravenously, the outcomes of the baseline economic analysis
revealed that the treatment cost for patients randomized to receive FLU was
approximately 50% higher than that for patients treated with AMB [AMB: $Can2370
vs FLU: $Can3578; p = 0.001 ($Can = Canadian dollars)]. In the sensitivity
analysis, substitution to oral FLU after 7 days of intravenous therapy produced
economic differences that were no longer statistically significant (AMB: $Can2370
vs FLU: $Can2705; p = 0.10). These results suggest that the FLU administration
regimen used in the Canadian randomized trial for the treatment of candidemia in
non-neutropenic patients may result in increased hospital costs compared with
AMB. However, comparable expenditures could be realized if FLU is administered
intravenously for the first 7 days and then orally in patients whose condition
allows for reliable oral therapy.
PMID- 10180752
TI - Linking the health utilities index to National Medical Expenditure Survey data.
AB - Measures of health-related quality of life (HR-QOL) are becoming increasingly
important in assessing the effects of chronic illness and healthcare
interventions designed to treat them. Obtaining measures of HR-QOL for a
nationally representative sample of individuals would enhance understanding of
health status in the US, and promote further study of the economic causes and
effects of health status. This study reports on our efforts to link a prominent
HR-QOL scale, the Health Utilities Index Mark I (HUI), to the National Medical
Expenditure Survey (NMES). Six distinct algorithms were constructed for linking
the HUI to NMES. These alternative linkage algorithms yielded HUI measures that
were highly intercorrelated (p = 93 to 99%). Multivariate regression analyses
performed to predict variations in HR-QOL revealed that the HUI exhibited good
predictive validity--the HUI demonstrated lower quality of life for a variety of
chronic illnesses, and wealthier individuals and better educated individuals had
a higher quality of life. In contrast to some previous HR-QOL research, the
present analysis demonstrates that: (i) cancer is negatively and significantly
related to quality of life; and (ii) smoking is negatively and significantly
related to quality of life. Overall, the results suggest that the HUI linkages to
NMES provide reliable and valid measures of quality of life. As such, items from
the NMES can be grouped and linked in such a way as to obtain health state
utility values. These values should be of use to those who wish to understand the
global health of the US population for policy-making efforts.
PMID- 10180754
TI - How to calculate indirect costs in economic evaluations.
PMID- 10180755
TI - Doctor sends patients home with a video camera to get a better view of asthma.
PMID- 10180756
TI - Prison telemedicine gets an enthusiastic thumbs up--from the inmates.
PMID- 10180753
TI - Fluoxetine. A pharmacoeconomic review of its use in depression.
AB - Depressive illness is a common, often unrecognised and untreated condition with
substantial associated costs, particularly indirect costs (e.g. lost productivity
and absenteeism). The improved tolerability profile of fluoxetine and associated
lower discontinuation rates, the relative safety of the drug in overdosage and
its similar efficacy compared with tricyclic antidepressants have provided the
main rationale for using this agent in depressed patients. Pharmacoeconomic
analyses of fluoxetine have mainly sought to determine whether its higher
acquisition cost in comparison with tricyclic antidepressants can be offset by
reductions in other costs and whether the use of this agent as first-line therapy
can be justified. Studies have also attempted to determine whether the selective
serotonin reuptake inhibitors (SSRIs) can be distinguished from one another on
pharmacoeconomic grounds; overall efficacy and tolerability of these agents
appear to be similar, although tolerability data are conflicting. Most analyses
have been of a retrospective database or clinical decision analytic model design;
two prospective trials (one conducted in a naturalistic setting) have been
conducted. These studies have mainly considered direct treatment costs only from
the perspective of the healthcare payer. Available evidence suggests that overall
total direct healthcare costs for patients who start antidepressant therapy with
fluoxetine are similar to, or lower than, those for patients who start therapy
with tricyclic agents or other SSRIs. Offsetting of the higher acquisition cost
of fluoxetine compared with that of tricyclic agents may be accounted for by
lower in- and outpatient costs with fluoxetine, a possible lower risk of
absenteeism from work and lower mean total medical costs associated with acute
overdosage. Between-treatment differences in drug use patterns may also, in part,
explain the observed differences in total healthcare costs between fluoxetine and
other antidepressants. In particular, patients beginning therapy with fluoxetine
are more likely to receive treatment regimens that meet minimum recommended
guidelines for dosage and duration and are less likely to require treatment
switching/augmentation than those receiving tricyclic antidepressants or other
SSRIs as initial therapy. In addition, fewer fluoxetine than tricyclic
antidepressant recipients discontinue therapy early, and fewer fluoxetine
recipients require upward dosage titration or concomitant anxiolytic/ hypnotic
medications than patients receiving other SSRIs. In conclusion, fluoxetine is a
well established antidepressant which possesses tolerability and safety
advantages over the tricyclic agents. The available cost analyses show that these
benefits can be obtained without additional overall cost to the healthcare
provider. Cost advantages observed to date for fluoxetine over other SSRIs
require confirmation.
PMID- 10180757
TI - Northern Arizona area expands telepsychiatry services.
PMID- 10180758
TI - In-patient care saves money with telemedicine, but out-patient services are
needed.
PMID- 10180759
TI - The AFIP center for telemedicine application--pathology for the twenty-first
century.
PMID- 10180760
TI - Telemedicine links from U.S. to Russia work as a two-way information street.
PMID- 10180761
TI - Italian hospitals connect to Bosnia, Albania.
PMID- 10180763
TI - Testing center develops teleradiology via the Internet.
PMID- 10180762
TI - Telemedicine project helps clean up rocket fuel in Ukraine.
PMID- 10180764
TI - Air Force Base saves money using telemedicine.
PMID- 10180766
TI - Physio-control defibrillators on Varig aircraft.
PMID- 10180765
TI - No one applies for California telemedicine reimbursement.
PMID- 10180767
TI - Dalhousie medical school exports telemedicine services.
PMID- 10180768
TI - Industry donations complete "last mile" so tiny hearts can get expert care.
PMID- 10180770
TI - Health on the net lists operating principles.
PMID- 10180769
TI - Cancer lecture is first telemedicine link from Lebanon.
PMID- 10180771
TI - Frost & Sullivan sees growing strength of videoconferencing.
PMID- 10180772
TI - The vital data that fire tests fail to provide.
PMID- 10180773
TI - NHS achieves world first in environmental management.
PMID- 10180774
TI - The medical device directive.
PMID- 10180775
TI - Access control systems--an estate officer's view.
PMID- 10180776
TI - Public sector year 2000 problem.
PMID- 10180777
TI - Fear of fraud. Could restocking ambulances put hospitals in jeopardy? Good
question.
PMID- 10180778
TI - Hostile world.
PMID- 10180779
TI - Shortcuts. Electronic commerce pays off.
PMID- 10180781
TI - Walk the talk: power up your empowerment program.
PMID- 10180780
TI - Gloves off! Dust rises over powdered vs. powder-free gloves.
PMID- 10180782
TI - Stats. Ambulatory surgery isn't ouchless.
PMID- 10180783
TI - The quick look airway classification. A useful tool in predicting the difficult
out-of-hospital intubation: experience in an air medical transport program.
AB - The unpredictable nature of the out-of-hospital care environment poses unique
challenges for active airway management techniques. This descriptive study was
conducted in the helicopter air medical transport (AMT) environment for a period
of 32 months to determine whether initial direct airway visualization
classification may provide a useful tool to predict the difficulty of intubation.
Data extracted from documented oral intubation attempts included initial airway
visualization grade, number of attempts, final airway management method, and
procedural complications. Oral intubation was attempted on 429 patients. Initial
airway visualization grades were found with the following frequency for grades I
through IV: 65.6%, 21.5%, 8.6%, and 5.4%, respectively. Similarly, the average
number of attempts was 1.34, 1.65, 1.97, and 2.39, respectively. The serious
complication rate was 24%, 46%, 62%, and 65%, respectively. A statistically
significant correlation (Spearman's rho) was found between increasing grade and
both the number of intubation attempts (0.52) and the number of complications
(0.45). Initial visualization classification may serve as a useful indicator in
the out-of-hospital environment to help anticipate the difficulty of intubation
and the need for early alternative airway management strategies. In this program,
such classification is used to monitor airway management skills.
PMID- 10180784
TI - Air medical referring customer satisfaction: a valuable insight.
AB - INTRODUCTION: To remain competitive and survive, air medical programs must have a
mechanism for obtaining customer feedback, especially when alternate transport
options are available. The goal of this survey was to examine the air medical
service's performance as perceived by customers requesting the transport.
METHODS: Surveys were mailed to 400 referring customers who had contact with the
flight crew during the transition of patient care. The survey consisted of 16
statements evaluating the service by using a 4-point Likert scale, three
demographic questions, one statement evaluating overall satisfaction, and two
open-ended questions for comments or suggestions. RESULTS: Two hundred forty-four
surveys were returned for a 61% responses rate. Results indicated referring
customers are satisfied with the service provided Written comments and
suggestions were divided into two categories, positive comments and suggestions
for improvement. Three common themes were identified within the suggestions for
improvement: crew rapport, communications, and operations. Suggested improvements
were evaluated, and selected strategies were incorporated into program operation.
CONCLUSION: Customer feedback furnishes valuable insight into their needs and
perception of a service. Comments and suggestions for improvement can promote
critical inquiry into service operation and provide a catalyst for improvement.
PMID- 10180785
TI - The making of helicopters: its strategic implications for EMS helicopter
operations.
AB - PURPOSE: The purpose of this article is to provide EMS helicopter personnel with
an understanding of the civil helicopter manufacturing industry. Specifically,
this article examines the current helicopter marketplace and how various
manufactures are responding to the recent decline in new helicopter sales. This
article further describes how helicopters are designed and manufactured and how
global markets, international competition, and strategic considerations are
influencing future helicopter design and production. METHODS: Data for this paper
were obtained from a literature search through the ABI-inform Telnet Services
offered through the University of Utah Marriott Library. On a search of
"helicopter" during the past 5 years, 566 abstracts were identified, all of which
were reviewed for information related to the purpose of this article. Forty-seven
articles were identified and read in detail for information that may have related
to the purpose of this article. In addition, a library search to identify
textbooks that describe helicopter production systems was undertaken but did not
identify any written resources. Because of the lack of written resources
available in writing this article, a direct interview survey of leading
helicopter manufactures, associations, and industry writers was conducted. Only
information that was considered "public knowledge" was available because of
concerns by the various manufactures that publication of confidential information
could be detrimental to their competitive advantage. LIMITATIONS: Because
helicopter-manufacturing plants were not located within easy travel range, no
direct observation of the production facilities could be undertaken. Furthermore,
information regarding production and operational management was not easily
accessible because the data were not published or were considered confidential.
Therefore industry analysis had to take place through direct survey interviewing
technique and data obtained through an analysis of the available published data.
PMID- 10180786
TI - Basics of research (Part 12): Qualitative research.
AB - Although both the assumptions and methods of qualitative and quantitative
approaches in nursing research are different, both have the goal of furthering
the scientific basis for practice. A variety of qualitative approaches are
available, and which approach to use depends on the purpose of the research. In
general, qualitative investigations address broad questions related to
description, discovery, or theory building, and, as a consequence, the researcher
is concerned with the entire context surrounding the phenomenon of interest
rather than concentrating on specific variables thought to influence that
phenomenon. The type of data collected and the methods of analysis differ, but
qualitative research demands the same careful attention to selecting a design
appropriate to answer the research question and the same assurance of rigor in
conducting the research and interpreting the results as is required in
quantitative studies. When these issues are thoroughly addressed, the clinician
has a basis for judging both the accuracy and the applicability of qualitative
research findings.
PMID- 10180787
TI - Business principles for air medical professionals. Part 1: Can you be self
employed?
PMID- 10180788
TI - Narcotics and controlled drugs: a secure system for access by transport teams.
PMID- 10180791
TI - Moral quality entails a high standard of informed consent.
PMID- 10180789
TI - Management of colorectal cancer.
PMID- 10180790
TI - Effective management of stable angina.
PMID- 10180792
TI - Inquiry into the potential value of an information pamphlet on consent to surgery
to improve surgeon-patient communication.
AB - OBJECTIVES: To find out how patients recently undergoing surgery experienced the
consenting process and the response of these patients to a pamphlet on consent to
surgery. To test the reaction of health professionals to the pamphlet. DESIGN: A
pilot pamphlet was produced and a questionnaire was sent to patients inquiring
about their consenting experience, and how the pamphlet might have helped them
through the consent procedure. A pamphlet and a questionnaire were also sent to a
random sample of the health professionals serving these patients. SUBJECTS:
Patients and health professionals. RESULTS: 61% of patients returned the
questionnaire. Knowledge about the consent procedure was shown to be limited. 49%
were unaware that they had the right to insist that the surgeon could only
perform the specified operation and nothing more. 83% were unaware that they
could add something in writing to the consent form before signing. 28% of health
professionals returned their questionnaire, most of whom thought that the
pamphlet provided a useful contribution to surgeon-patient communication.
CONCLUSION: Evidence shows that patients are not well informed about consenting
to surgery and further information would provide much needed guidance on
understanding their role in the consent procedure. The low response from the
health professional study is perhaps an indication that at present this is an
issue which is not seen as a priority.
PMID- 10180793
TI - Staff and patient feedback in mental health services for older people.
AB - OBJECTIVES: To compare the views of patients and staff on the quality of care
provided on a psychogeriatric assessment ward over a five year period. To
describe the quality improvements which were made as a result of their respective
comments. DESIGN: Structured interviews were conducted with both patients and
staff to obtain qualitative feedback and suggestions for improvement. An analysis
of the percentage of positive and negative comments made by both patients and
staff was used to compare the levels of satisfaction on a variety of aspects of
the service provided. SETTING: Psychogeriatric inpatient assessment ward.
SUBJECTS: 75 patients and 85 staff interviews were conducted. MAIN MEASURES:
Structured interviews covering various aspects of service quality. RESULTS: Staff
and patients picked up on different aspects of service quality as important.
Quality improvements which arose from the interviews were clearly different.
Generally patients were more positive about the physical environment and
standards of professional care than staff, but less positive about issues of
privacy, social interaction, and empowerment. CONCLUSIONS: The perspectives of
patients and staff in this area are not interchangeable. Both series of
interviews led to several positive changes in the quality of care. Interviews
with staff seem to have been valuable in a low morale situation. A structured
interview format provided patients with an opportunity to feedback openly and led
to changes in service quality which would not otherwise have occurred.
PMID- 10180794
TI - Quality of midwifery led care: assessing the effects of different models of
continuity for women's satisfaction.
AB - BACKGROUND: Changing Childbirth (1993), a report on the future of maternity
services in the United Kingdom, endorsed the development of a primarily community
based midwifery led service for normal pregnancy, with priority given to the
provision of "woman centred care". This has led to the development of local
schemes emphasising continuity of midwifery care and increased choice and control
for women. AIMS: To compare two models of midwifery group practices (shared
caseload and personal caseload) in terms of: (a) the extent to which women see
the same midwife antenatally and know the delivery midwife, and (b) women's
preference for continuity and satisfaction with their care. METHODS: A review of
maternity case notes and survey of a cohort of women at 36 weeks of gestation and
2 weeks postpartum who attended the two midwifery group practices. Questionnaires
were completed by 247 women antenatally (72% response) and 222 (68%) postnatally.
Outcome measures were the level of continuity experienced during antenatal,
intrapartum, and postnatal care, women's preferences for continuity of carer, and
ratings of satisfaction with care. RESULTS: The higher level of antenatal
continuity of carer with personal caseload midwifery was associated with a lower
percentage having previously met their main delivery midwife (60% v 74%). Women's
preferences for antenatal continuity were significantly associated with their
experiences. Postnatal rating of knowing the delivery midwife as "very important
indeed" was associated with both previous antenatal ratings of its importance,
and women's actual experiences. Personal continuity of carer was not a clear
predictor of women's satisfaction with care. Of greater importance were women's
expectations, their relations with midwives, communication, and involvement in
decision making. CONCLUSIONS: Midwifery led schemes based on both shared and
personal caseloads are acceptable to women. More important determinants of
quality and women's satisfaction are the ethos of care consistency of care, good
communication, and participation in decisions.
PMID- 10180795
TI - Assessing local health needs in primary care: understanding and experience in
three English districts.
AB - BACKGROUND: Assessing the health needs of a local population has been promoted as
a key component in effective targeting of healthcare services and quality
improvement. The understanding and experience of assessing health needs in
general practice were investigated in three English districts. AIM: To identify
the issues surrounding the potential for assessing health needs in primary care.
METHOD: Postal survey of 347 general practices in three health authorities.
Telephone interviews with a random stratified sample of 35 general practitioners.
RESULTS: Although most practices identified assessing health needs as important,
it is clear that this identification was typically based on an understanding of
assessing needs as primarily focused on individual patient care, based on
clinical priorities and involving practice held data. Most practices had not
undertaken local consultation, whatever their understanding of assessing health
needs. The few practices which had completed population oriented, proactive
assessment of needs considered it to have led to tangible improvements in
clinical or practice management. Overall, there was apparent confusion over the
nature and purpose of assessing needs, although the principled aims and
objectives of a population oriented, proactive component to primary care were
generally upheld. The need for additional resources and support was identified.
In four out of the five cases where specifically population based assessment of
health needs had been undertaken, the local public health department had been
involved. CONCLUSION: The value of the concept of assessing health needs in
primary care holds considerable uncertainty and ambivalence. The findings from
this study show that any attempts to promote assessing needs into primary care
which focus either primarily or exclusively on the provision of "education" are
unduly simplistic. More fundamental questions about the perceived relevance and
opportunities for assessing health needs should be considered if primary care
groups are to meet future commissioning challenges.
PMID- 10180796
TI - What do health authorities think of population based health outcome indicators?
AB - OBJECTIVES: To determine the role of population based indicators of health
outcome in local health outcome assessments; the constraints of using such
indicators; how they could be made more useful; and whether health authorities
had developed their own indicators of health outcome. DESIGN: A structured
telephone interview with representatives of 91 of the 100 English health
authorities. RESULTS: Interviewees, asked to give details on two clinical areas
in which population health outcome assessments had been of most value, nominated
147 examples in over 30 clinical areas. They chose 50 (34%) of the examples
because of an outlying national indicator, and 20 (14%) because of local
variations in a national indicator. The main perceived constraints in the use of
population based indicators of health outcome were: data validity and timeliness;
the attributability of these health outcomes to the quality of health care; the
difficulties of changing clinical behavior; and organisational change within
health authorities. To make these indicators more useful interviewees wanted an
increased use of process indicators as proxies for health outcome, indicator
trend data, and indicator comparisons of districts with similar population
structures. Some recent publications have started to consider some of these
issues. 27 (30%) health authorities had developed their own indicators, mostly
provider based process indicators. 10 of these used their own indicators to
manage the performance of local provider units. CONCLUSIONS: Population based
indicators of health outcome had an important role in prompting districts to
undertake population health outcome assessments. Health authorities also used
these indicators to examine local variations in health outcome. They helped to
highlight areas for further investigation, initiated data validation, and enabled
the monitoring of changes to services. Comparative population based indicators of
health outcome may have an increasing part to play in assessing the performance
of health authorities.
PMID- 10180797
TI - Public participation and the moral quality of healthcare rationing.
PMID- 10180798
TI - Why people select health plans.
PMID- 10180799
TI - Compensation monitor. AMA: doctors' income still rising.
PMID- 10180800
TI - Squeezing through HMOs' rough times.
PMID- 10180801
TI - Does mail-order pharmacy really deliver the goods?
PMID- 10180802
TI - A conversation with Margaret T. Stanley.
PMID- 10180803
TI - This IPA's slide toward ruin could have been prevented.
PMID- 10180804
TI - Is sex medically necessary? Who should pay for Viagra?
PMID- 10180806
TI - Managed care outlook. Managed medical care growth rubs off on dentistry.
PMID- 10180805
TI - Stark II: division of profits comes under closer scrutiny.
PMID- 10180807
TI - HCFA clarifies PPS claims processing delay, other PPS issues.
PMID- 10180808
TI - Providers seek detail on PPS rate components; HCFA offers some answers.
PMID- 10180809
TI - Raising red flags: likely areas for focused medical review under PPS.
PMID- 10180810
TI - Strategies for dealing with SNF PPS will vary depending upon individual
circumstances; nine possible scenarios.
PMID- 10180811
TI - SNFs to use new revenue, insurance codes for billing under PPS.
PMID- 10180812
TI - Life in the fast lane. The anything-but-normal life of a GHA lobbyist.
PMID- 10180813
TI - Medicaid: a reason to unite.
PMID- 10180814
TI - Hospitals and the millennium bug.
PMID- 10180815
TI - DMA chief pleased with DRG process, outcome.
PMID- 10180816
TI - Is health care a right?
PMID- 10180817
TI - IRS joint venture ruling stresses nonprofit's control.
PMID- 10180818
TI - GHA's data services team.
PMID- 10180819
TI - It's the budget, stupid!
PMID- 10180820
TI - Assessing family satisfaction with care for persons with dementia.
PMID- 10180821
TI - Factors affecting the growth of assisted living.
PMID- 10180822
TI - Subacute accreditation survey follows new protocol.
PMID- 10180823
TI - Change requires some "tough" with the "tender".
PMID- 10180824
TI - Secure your bottom line by going above and beyond.
PMID- 10180825
TI - Become your own mentor.
PMID- 10180826
TI - ACHCA best practices: ideas you can use!
PMID- 10180827
TI - What do residents really need?
PMID- 10180829
TI - Capitalizing on diversity makes good business sense.
PMID- 10180828
TI - The budget resolution: the devil's in the details.
PMID- 10180830
TI - DM carve-outs soften sticker shock of catastrophic care.
PMID- 10180831
TI - Prevention, education programs head off high cost of stroke.
AB - Stroke is the nation's third leading cause of death and represents a human as
well as a financial catastrophe. Find out how these DM programs are identifying
patients with specific risk factors for stroke, teaching patients about the
disease and its warning signs, and following up with multidisciplinary
management.
PMID- 10180832
TI - Voice-activated phone system improves diabetes self-care, cuts blood glucose
levels.
AB - Automated telephone monitoring can be significantly cheaper and actually more
"user friendly" than the one-to-one nurse-patient phone call. Find out how one
system is using monitoring technology to achieve superior compliance rates for
diabetes testing while bringing down NbA1c levels.
PMID- 10180833
TI - Move forward with prostate Ca education despite lack of consensus over screening.
AB - Prostate cancer screening may be a subject of debate for your health plan, but a
lack of consensus on this issue shouldn't preempt efforts to educate patients
about the disease and let them decide, with their doctor, about the best
prevention strategy. Get the details behind a quality initiative that's putting
the decision in patients' hands while also gathering data on the cost
effectiveness of screening efforts.
PMID- 10180834
TI - With little to go on but much to gain, small IPA starts asthma DM program.
PMID- 10180835
TI - Perspectives. Tobacco deal: does the equation balance?
PMID- 10180836
TI - Perspectives. States forge ahead of feds on parity.
AB - A Cabinet-level recommendation is expected soon on whether employers will be
allowed to seek exemption from federal mental health parity-of-coverage
requirements based on prospective or retrospective calculations of their
compliance costs. The law provides exemption for plan sponsors whose parity costs
exceed 1 percent of their total health spending. Meanwhile, though, many states
are forging ahead with parity laws of their own, while advocates see the federal
law as only a modest prelude.
PMID- 10180837
TI - Perspectives. "Carving in" is the cutting edge of managed Medicaid mental health
care.
PMID- 10180838
TI - Perspectives. Wall Street verbatim: wider networks need not drive new cost
explosion.
PMID- 10180839
TI - Perspectives. Medicare 'Mega-reg' adds to challenges faced by new plans hoping to
compete.
PMID- 10180840
TI - Case mix measurement in English hospitals: an evaluation of five methods for
predicting resource use.
AB - OBJECTIVES: The introduction of an internal market in the British National Health
Service (NHS) has highlighted the importance of developing appropriate, valid and
timely measures of hospital activity, both for the purposes of specifying and
monitoring contracts and for evaluating the success of the NHS reforms in
general. This paper compares the validity of five case mix methods (Diagnosis
Related Groups (DRGs); Healthcare Resource Groups (HRGs) versions 1 and 2;
specialty classification; a simple age categorization) in predicting resource
use. METHODS: Two data sets were used to compare different case mix methods. A 3%
random sample (n approximately equal to 300,000) of the 1992/3 Hospital Episodes
Statistics was used to test their ability to predict variation in length of stay,
and a second set of individually costed patient episodes from two hospitals (n
approximately equal to 40,000) was used to test their ability to explain cost
variation. Analysis of variance models were used to assess the fit of each of the
case mix systems to test data and a simple significance test of differences in
mean squared error between models was applied. RESULTS: All case mix methods
performed poorly on untrimmed data. When lengths of stay greater than 29 days
were excluded, version 2 of HRGs explained 31% of total variance in length of
stay and 25% of cost variation. DRGs explained less variance but performed better
than HRGs version 1. For a typical hospital patient population consisting of a
range of specialties, the difference in explanatory power between HRGs V2 and
DRGs was statistically significant at the 5% level for sample sizes of
approximately 2000 or greater. For individual specialties, the minimum sample
size required for the difference between the groupers to be significant ranged
from around 300 to over 2000. CONCLUSIONS: The locally developed HRGs version 2
system appears to offer superior performance in terms of resource homogeneity to
other currently available approaches. It is also more adaptable and cheaper than
imported alternatives and has been formally endorsed by the UK medical Royal
Colleges.
PMID- 10180841
TI - Measurement of overall and disease-specific health status: does the order of
questionnaires make a difference?
AB - OBJECTIVES: This study was designed to detect any effect of order when modules on
disease-specific and overall health status are combined in an outcomes research
questionnaire. METHODS: Men with symptomatic benign prostatic hyperplasia (BPH)
were prospectively enrolled in a clinical trial of an educational intervention in
Group Health Cooperative of Puget Sound, a prepaid group practice. Within the
trial, 392 consecutive men were randomized to one of two versions of a baseline
questionnaire. One had a 38-item module on BPH-specific health status first,
followed by a 30-item module on overall health status; the other had the modules
in reverse order. Scores were compared for three BPH-specific scales and eight
scales measuring overall health. Data were collected in the form of self
administered questionnaires. RESULTS: Comparing the groups assigned the two
versions of the questionnaire, no significant differences in scores on any of the
health status scales were found. CONCLUSIONS: In this dataset, we could find no
evidence of an order effect when modules on BPH-specific and overall health
status were combined in different sequences.
PMID- 10180842
TI - Knowledge based commissioning: can a national clinical effectiveness policy be
compatible with seeking local professional advice?
AB - OBJECTIVES: To help develop a means, based on the views of purchasers and
providers of health care, of incorporating national research on clinical
effectiveness into local professional advisory mechanisms in order to inform
health care purchasing and contracting. METHODS: Three geographically based
multidisciplinary workshops attended by National Health Service (NHS) staff drawn
from the principal purchaser and provider groups in one English region were
organized around the discussion of three health care purchasing case studies:
coronary artery disease, diabetes and management of clinical depression in
general practice. The proceedings were transcribed and analyzed using content
analysis methods. RESULTS: 95 people took part. There were major differences
between the purchasers' and health care providers' views on the right balance
between local and national information and advisory sources for purchasing. In
general, providers wanted the provision of advice to purchasers to be local, in
which their opinion was sought, either individually or collectively, acted on and
the results fed back to them. In contrast, health authority purchasers considered
that local professionals were only one source of professional advice, albeit an
important one, to be utilized in coming to decisions. General practitioner
fundholders as purchasers, however, preferred to rely on their own experiences
and contacts with local providers in making purchasing decisions. CONCLUSIONS:
Professional specialist advisory groups are necessary to inform the purchasing of
health care, but should extend beyond advising on the placement of individual
contracts. Involving health care providers in all short-term contracting is
unlikely to be cost-effective given the time commitment required. The emphasis at
purchaser/provider meetings should be on education: providing an opportunity for
purchasers and providers to develop closer relationships to discuss political
imperatives and financial constraints; increasing communication and understanding
of providers' and purchasers' roles; and providing an environment for
professionals and purchasers to share their views on purchasing. As currently
presented, elements of the national policies in the NHS advocating the use of
both national evidence on clinical effectiveness and local professional advice
are contradictory and should be clarified.
PMID- 10180843
TI - How can payback from health services research be assessed?
AB - Throughout the world there is a growing recognition that health care should be
research-led. This strengthens the requirement for expenditure on health services
research to be justified by demonstrating the benefits it produces. However,
payback from health research and development is a complex concept and little used
term. Five main categories of payback can be identified: knowledge; research
benefits; political and administrative benefits; health sector benefits; and
broader economic benefits. Various models of research utilization together with
previous assessments of payback from research helped in the development of a new
conceptual model of how and where payback may occur. The model combines an input
output perspective with an examination of the permeable interfaces between
research and its environment. The model characterizes research projects in terms
of Inputs, Processes, and Primary Outputs. The last consist of knowledge and
research benefits. There are two interfaces between the project and its
environment. The first (Project Specification, Selection and Commissioning) is
the link with Research Needs Assessment. The second (Dissemination) should lead
to Secondary Outputs (which are policy or administrative decisions), and usually
Applications (which take the form of behavioural changes), from which Impacts or
Final Outcomes result. It is at this final stage that health and wider economic
benefits can be measured. A series of case studies were used to assess the
feasibility both of applying the model and the payback categorization. The paper
draws various conclusions from the case studies and identifies a range of issues
for further work.
PMID- 10180844
TI - Failure of health care reform in the USA.
AB - The failure of health reform in the USA reflects the individualism and lack of
community responsibility of the American political culture, the power of interest
groups, and the extraordinary process President Clinton followed in developing
his highly elaborate plan. Despite considerable initial public support and a
strong start, the reform effort was damaged by the cumbersome process, the
complexity of the plan itself, and the unfamiliarity of key components such as
alliances for pooled buying of health insurance. In addition, the alienation of
important interest groups and the loss of presidential initiative in framing the
public discussion as a result of international, domestic and personal issues
contributed to the failure in developing public consensus. This paper considers
an alternative strategy that would have built on the extension of the Medicare
program as a way of exploring the possibilities and barriers to achieving health
care reform. Such an approach would build on already familiar and popular pre
existing components. The massive losses in the most recent election and large
budget cuts planned by the Republican majority makes it unlikely that gaps in
insurance or comprehensiveness of coverage will be corrected in the foreseeable
future.
PMID- 10180845
TI - Structural change in hospitals: the implications for research.
AB - This paper begins by considering briefly the interdependent nature of the health
care sector and suggests that most research on structural change in the hospital
system has ignored that obvious fact. It then goes on to argue that this failure
will become even more significant in the face of the large scale changes that are
expected in the way health services are delivered. Its central proposal is that
the research horizons should be widened, particularly if change on the scale that
appears likely is to be properly evaluated. How that may be done is considered in
the final section.
PMID- 10180846
TI - Assessing appropriateness of care.
PMID- 10180847
TI - Where do internal markets come from and can they work?
AB - The basis for the argument in favour of the internal market as a means of
allocating resources within the health care sector has never been made fully
explicit. In particular, the link between the economic theory of market
allocation and the specific pricing rules adopted by a number of health care
sectors to allocate resources is rarely a focus of attention. Health sector
objectives are rarely specified. The mechanisms which remedy failure in the
exchange process are not explicitly defined. In short, the optimal structural
conditions for the operation of internal markets are not known. The central
argument pursued here is that, as this is the case, and using the UK as an
example, there are no criteria to which purchasers or providers can turn to
assess the operation of exchange within the internal market. Not surprisingly,
the internal market dissolves into a number of individual bilateral agreements
between purchasers and providers which may or may not increase efficiency in
allocating health sector resources.
PMID- 10180848
TI - 'Evidence-based', 'cost-effective' and 'preference-driven' medicine: decision
analysis based medical decision making is the pre-requisite.
AB - Three broad movements are seeking to change the world of medicine. The proponents
of 'evidence-based medicine' are mainly concerned with ensuring that strategies
of proven clinical effectiveness are adopted. Health economists are mainly
concerned to establish that 'cost-effectiveness' and not 'clinical effectiveness'
is the criterion used in determining option selection. A variety of patient
support and public interest groups, including many health economists, are mainly
concerned with ensuring that patient and public preferences drive clinical and
policy decisions. This paper argues that decision analysis based medical decision
making (DABMDM) constitutes the pre-requisite for the widespread introduction of
the main principles embodied in evidence-based medicine, cost-effective medicine
and preference-driven medicine; that, in the light of current modes of practice,
seeking to promote these principles without a prior or simultaneous move to
DABMDM is equivalent to asking the cart to move without the horse; and that in
fact DABMDM subsumes and enjoins the valuable aspects of all three. Particular
attention is paid to differentiating between DABMDM and EBM, by way of analysis
of various expositions of EBM and examination of two recent empirical studies.
EBM, as so far expounded, reflects a problem-solving attitude that results in a
heavy concentration on RCTs and meta-analyses, rather than a broad decision
making focus that concentrates on meeting all the requirements of a good clinical
decision. The latter include: ensuring that inferences from RCTs and meta
analyses to individual patients (or patient groups) are made explicitly; paying
equally serious attention to evidence on values and costs as to clinical
evidence; and accepting the inadequacy of 'taking into account and bearing in
mind' as a way of integrating the multiple and distinct elements of a decision.
PMID- 10180849
TI - Methods of health services evaluation: the gospel of Archie Cochrane after 25
years.
PMID- 10180850
TI - The contingent valuation controversy in environmental economics and its relevance
to health services research.
PMID- 10180851
TI - Why should health services be primary care-led?
AB - A primary care-led health service is the latest fashion in health policy, yet
there is no consensus on what this means. One manifestation of this policy is the
attempt to shift the balance of resources from secondary to primary care, with
the goal of improving the cost-effectiveness of health care. This has been taken
furthest in the UK, where GP fundholders have been given resources to purchase a
significant proportion of their patients' health care. The scheme provides
incentives to shift the location of care out of hospitals, but there is very
little evidence that this will result in better quality patient care at lower
cost.
PMID- 10180852
TI - Does severity explain differences in hospital length of stay for pneumonia
patients?
AB - OBJECTIVES: In the USA, the role of patient severity in determining hospital
resource use has been questioned since Medicare adopted prospective hospital
payment based on diagnosis-related groups (DRGs). Exactly how to measure
severity, however, remains unclear. We examined whether assessments of severity
adjusted hospital lengths of stay (LOS) varied when different measures were used
for severity adjustment. METHODS: The complete study sample included 18,016
patients receiving medical treatment for pneumonia at 105 acute care hospitals.
We studied 11 severity measures, nine based on patient demographic and diagnosis
and procedure code information and two derived from clinical findings from the
medical record. For each severity measure, LOS was regressed on patient age, sex,
DRG, and severity score. Analyses were performed on trimmed and untrimmed data.
Trimming eliminated cases with LOS more than three standard deviations from the
mean on a log scale. RESULTS: The trimmed data set contained 17,976 admissions
with a mean (S.D.) LOS of 8.9 (6.1) days. Average LOS ranged from 5.0-11.8 days
among the 105 hospitals. Using trimmed data, the 11 severity measures produced R
squared values ranging from 0.098-0.169 for explaining LOS for individual
patients. Across all severity measures, predicted average hospital LOS varied
much less than the observed LOS, with predicted mean hospital LOS ranging from
about 8.4-9.8 days. DISCUSSION: No severity measure explained the two-fold
differences among hospitals in average LOS. Other patient characteristics,
practice patterns, or institutional factors may cause the wide differences across
hospitals in LOS.
PMID- 10180853
TI - Problems with recruitment in a randomized controlled trial of counselling in
general practice: causes and implications.
AB - OBJECTIVES: To evaluate the effectiveness of counselling in the management of
minor psychiatric morbidity in general practice, and to explore the reasons for
difficulties in recruiting patients to such an evaluation. METHODS: We attempted
to conduct a randomized controlled trial of counselling in eight general
practices in one NHS family health services authority area in England. Having
experienced significant problems recruiting patients, we conducted semi
structured telephone interviews (n = 8) with participating GPs to explore the
reasons for these difficulties. RESULTS: Five months after the start of the study
only one patient had been recruited. The main reasons identified as contributing
to the recruitment problems were: general practitioners' motivation for
involvement in the study; their ethical doubts about the randomization process;
the perceived lack of a viable non-counselling intervention; and their existing
practical commitment to counselling. CONCLUSION: Although methodological
modification might enhance the potential for success in future studies of this
sort, more fundamental difficulties concerning general practitioners' attitudes
to research and their professional responsibilities lie at the heart of our
recruitment problems.
PMID- 10180854
TI - Planning the development of cystic fibrosis gene carrier screening.
AB - OBJECTIVES: It is now possible to test individuals to assess their cystic
fibrosis gene carrier status and a range of strategies for screening the
population have been piloted. The objective of this research was to develop a
planning framework which health care planners and purchasers can use to assess
the overall quantifiable outcomes and direct costs resulting from a year of
alternative screening strategies and the ways costs and outcomes evolve over
time. Beyond broader ethical and clinical considerations the information provided
by such a framework is needed to support decisions surrounding the development of
screening programmes. DESIGN: Operational Research modelling techniques were used
to develop the planning framework. To help illustrate the framework it was then
used to assess the quantifiable outcomes and direct costs of three of the main
alternative screening strategies: from antenatal clinics, '2-step' screening
where females are tested first followed by a screening invitation to the partners
of female carriers, and 'couple' screening where both partners must agree to be
tested at the outset; and from primary practice clinics 'active' contact of
attenders. Quantifiable outcomes are defined as the number of individuals
informed of their carrier status and the number of carriers, carrier couples, and
affected fetuses detected. Direct costs are those associated with the recruitment
and testing of individuals and the subsequent counselling of any gene carriers or
carrier couples identified. Results are based on services for a resident
population of 250,000 at two time points, year one and a year at 'steady state'.
RESULTS: The resultant framework estimates the number of individuals tested using
data on the size of the target population, the proportion of that population
alerted to the screening service, and the proportion who agree to be tested when
approached. Given service users, prevalence data are used to assess service
outcomes. Given the number of individuals approached and the subsequent demands
for services, service costs can be estimated. Preliminary results indicate that
in the short-term health care purchasers and planners who favour screening are
likely to opt for antenatal strategies. Although the high coverage of the primary
practice strategy leads to high outcomes in year one, relative to the antenatal
strategies, it also leads to very high costs. At 'steady state', cost and outcome
differences between the strategies are less marked. CONCLUSION: This paper
provides a framework which can be used to provide information to support decision
making surrounding the development of screening services. The methodology fills
an important void in the literature and complements research elsewhere by health
economists and by geneticists and their research colleagues. Preliminary findings
based upon use of the approach demonstrate the need for continued research to
further refine and improve the methodology.
PMID- 10180855
TI - A systematic review of the effectiveness of health service interventions aimed at
reducing inequalities in health.
AB - OBJECTIVE: To review the available evidence in order to identify effective
interventions which health services alone or in collaboration with other agencies
could use to reduce inequalities in health. METHODS: A search of the literature
was undertaken using a number of databases including Medline (from 1990), Applied
Social Science Index and Abstracts (1987-1994), and the System for Information on
Grey Literature in Europe (1984-1994), on a large range of key words. Studies
were included if they assessed interventions designed to reduce inequalities in
health or improve the health of a population group relevant to the review, and
could be carried out by a health service alone or in collaboration with other
agencies. Only studies evaluating interventions using an experimental design were
included. Papers in any language were considered. In addition, systematic reviews
of the research on the effectiveness of health promotion and the treatment of
conditions where there are significant health inequalities were identified in
order to illustrate the potential for reducing inequalities in health. RESULTS:
94 studies were identified which satisfied all the inclusion criteria and 21
reviews were included. A number of interventions have been shown to improve the
health of groups who are disadvantaged by socio-economic class, ethnicity or age
and, if properly targeted, could be expected to reduce health inequalities. If a
health intervention is being used, there should be evidence that it has an impact
on health status. Attention should then be given to the way in which the
intervention is delivered and the characteristics of a programme to promote
implementation. Characteristics of successful interventions specifically aimed at
reducing health differentials include: systematic and intensive approaches to
delivering effective health care; improvement in access and prompts to encourage
the use of services; strategies employing a combination of interventions and
those involving a multi-disciplinary approach; ensuring interventions address the
expressed or identified needs of the target population; and the involvement of
peers in the delivery of interventions. However, these characteristics alone are
not sufficient for success, nor are they universally necessary. CONCLUSIONS:
Although it is likely that the most significant contributions to reducing health
inequalities will be in improving economic and social conditions and the physical
environment, there are interventions which health services, either alone or in
collaboration with other agencies, can use to reduce inequalities in health.
PMID- 10180856
TI - The growth in emergency admissions--a challenge for health services research.
PMID- 10180857
TI - What do purchasers of health care want from health services research?
PMID- 10180858
TI - Predicting activity and workload in general practice from the demographic
structure of the practice population.
AB - OBJECTIVES: The managerial requirements of budget-setting and performance
monitoring in general practice (primary care) in the UK require an understanding
of the causal relationship between practice activities and the characteristics of
both the practice and its patients. This study sought to model the determinants
of three major components of general practice activities (consultations,
prescribing costs and referrals to secondary care), paying particular attention
to the influence of the demographic structure of the patient list. METHODS:
Stepwise regression analysis was carried out on data for 98 practices in the
county of Lincolnshire using 12 independent variables pertaining to patient and
practice characteristics plus 14 statistical measures derived from the
demographic structure of the patients registered with the practice. RESULTS:
Robust statistical models were estimated for the three dependent variables, of
which list size emerged as the most significant independent variable. In
addition, six other independent variables, including the patients' unemployment
rate, fundholding status and single-handed status, were statistically significant
in one or more of the equations. Variables based on the demographic structure of
the practice population also appeared in each model. The Jarman score and degree
of urbanization did not achieve statistical significance. CONCLUSIONS: Activity
and workload in general practice can be predicted from routine data. Such models
are of particular value for planning and financial management when demographic
change in practice populations is anticipated.
PMID- 10180859
TI - The costs of alternative types of routine antenatal care for low-risk women:
shared care vs care by general practitioners and community midwives.
AB - OBJECTIVES: To compare the costs to the health service, women and their families
of routine antenatal care provided by either traditional obstetrician-led shared
care or general practitioner (GP)/community midwife care. METHOD: A multicentre
randomized controlled trial in 51 general practices linked to nine maternity
hospitals in Scotland: 1667 low-risk pregnant women provided information on costs
to the health service. 704 of these women provided information on non-health
service costs. RESULTS: GP/midwife antenatal care was found to cost statistically
significantly less than shared care. This was the case for investigations carried
out at routine antenatal visits (GP/midwife = 87.25 Pounds, shared care = 91.15
Pounds, P = 0.05), staffing costs at routine antenatal visits (GP/midwife =
127.76 Pounds, shared care = 131.09 Pounds, P = 0.001), and non-health service
costs incurred by women and their companions (GP/midwife = 118.53 Pounds, shared
care = 133.49 Pounds, P = 0.001). While non-routine care in the GP/midwife arm of
the trial costs less than in the shared care arm, the difference was not
statistically significant (GP/midwife = 83.74 Pounds, shared care = 94.43 Pounds,
P = 0.46). The total societal cost of antenatal care was 417.28 Pounds per women
in the GP/midwife arm of the trial and 450.19 Pounds in the shared care arm of
the trial. This difference was statistically significant (P < 0.001). The
application of sensitivity analysis did not change these results. CONCLUSIONS:
GP/midwife antenatal care is a satisfactory option for low-risk pregnant women in
Scotland provided that clinical outcomes and women's satisfaction are at least
the same as those of women with shared care.
PMID- 10180860
TI - Using economics to prioritize research: a case study of randomized trials for the
prevention of hip fractures due to osteoporosis.
AB - OBJECTIVES: To assess the role of economics, in combination with clinical
judgement, for setting research priorities, using osteoporosis prevention (and,
as a result, hip fracture prevention) as an example. METHODS: Modelling the cost
and effectiveness of each of six potential interventions to prevent hip fractures
over the 5-year length of a randomized trial (vitamin D injection; thiazide
diuretics; hormone replacement therapy; oral calcium and vitamin D; calcium
alone; calcitonin). Drug costs were derived from the Monthly Index of Medical
Specialties (MIMS); averted fracture costs and estimates of effectiveness were
derived from published sources. RESULTS: Vitamin D injection proved to be the
most potentially cost-effective treatment with a cost-effectiveness ratio of 584
Pounds. If averted costs are included, this leads to a saving of 9,176,496 Pounds
per 100,000 women treated. By contrast, the most expensive therapy was calcitonin
(marginal cost-effectiveness ratio of 433,548 Pounds). This suggests that
priority should be given to trials assessing the effectiveness of vitamin D
injections. CONCLUSIONS: Relatively simple economic modelling exercises can
inform research priorities and could help optimize the use of scarce research
resources.
PMID- 10180861
TI - Programme budgeting and marginal analysis: an approach to priority setting in
need of refinement.
AB - Programme budgeting is enjoying a revival in the British National Health Service
primarily because of its recent coupling with marginal analysis. As well as
providing a means of mapping activity and expenditure from the institutions
providing care to the population receiving it, programme budgeting and marginal
analysis aim to assist strategic planning by indicating where net benefits might
be increased by reallocating spending within programmes. However, the method to
achieve this is not yet sufficiently refined and results to date have been mixed.
In particular, the approach to identifying options for evaluation is flawed
because of the importance attached to the role of 'expert' groups. A more
systematic technique is suggested to overcome present methodological
deficiencies.
PMID- 10180863
TI - Qualitative research methods.
PMID- 10180862
TI - Multilevel models: applications to health data.
AB - This paper presents an introductory account of multilevel models, highlighting
the potential benefits that may be gained by the use of these methods. It draws
on recent applications in health services research that have appeared in the
literature. Methodological advances in these statistical techniques have taken
place in the field of education, where empirical studies have mainly been
concerned with comparing pupil achievement across different schools by exploring
the relationship between individual and institutional factors. Although recent
widespread availability of suitable software packages has enabled other
disciplines to adopt these methods, to date they have received little attention
in the health services research literature (the investigation of effects of
geographical areas on health being a possible exception) despite their obvious
application in many areas of current interest. Key areas that could benefit
greatly from these techniques include the exploration of variations in clinical
practice, comparisons of institutional performance and resource allocation.
PMID- 10180864
TI - Policy-relevant health services research: who needs it?
PMID- 10180865
TI - What do we know about complementary medicine? What should we know?
PMID- 10180866
TI - May we support your decision?
AB - Expert systems to support medical decision-making have so far achieved few
successes. Current technical developments, however, may overcome some of the
limitations. Although there are several theoretical currents in medical
artificial intelligence, there are signs of them converging. Meanwhile, decision
support systems, which set themselves more modest goals than replicating or
improving on clinicians' expertise, have come into routine use in places where an
adequate electronic patient record exists. They may also be finding a wider role,
assisting in the implementation of clinical practice guidelines. There is,
however, still much uncertainty about the kinds of decision support that doctors
and other health care professionals are likely to want or accept.
PMID- 10180868
TI - What is 'development'?
PMID- 10180867
TI - Inequalities in health: what health systems can and cannot do.
AB - Health promotion activities are actively encouraged in most countries, including
the UK. Meanwhile many health care providers and health experts are becoming
increasingly concerned about the growing evidence of significant health
inequalities between social groups in the UK, and in particular the strong
association between relative deprivation and poor health. In 1995, a report for
the British government entitled 'Variations in health: what can the Department of
Health and the NHS do?', identified the need for the Department of Health and the
NHS to play a key role in coordinating and implementing public health programmes
intended to reduce inequalities in health. Examination of existing evidence on
the effectiveness of health promotion and prevention programmes designed to
improve the health status of the most vulnerable groups in society reveals very
little evidence to support current enthusiasm for adopting public health
strategies in order to reduce variations in health status between the affluent
and the poor. Alternative and potentially more effective health care responses to
inequalities in health status need to be considered.
PMID- 10180869
TI - Economics, public health and health care purchasing: the Tayside experience of
programme budgeting and marginal analysis.
AB - In this paper it is shown how the economics framework of programme budgeting and
marginal analysis (PBMA) can be used to help formulate a purchasing strategy in
health care; in this case, for child health services. The basic premise of PBMA
is that to have more of some services it is necessary to have less of others.
Therefore, it is important to know how resources are currently spent, what
changes can be made, and what are the possible costs and benefits of such
changes. Despite a lack of evidence on the effectiveness of services, PBMA
provides a pragmatic purchasing framework. This framework permits consideration
of national policy, local epidemiology, current spending, and the views both of
parents and professionals as to how such spending can be changed.
PMID- 10180870
TI - Patient preferences in randomised trials: threat or opportunity?
AB - OBJECTIVES: To assess whether it is feasible to elicit patients' preferences for
treatments and then to proceed with randomisation which may allocate those with
preferences to their less preferred treatment; and to describe which prognostic
variables were associated with such preferences within the context of a
randomised trial of an exercise programme for back pain. METHODS: The first 97
patients enrolled in a randomised controlled trial (RCT) for the treatment of
back pain were asked about their preferences, health characteristics and other
prognostic variables. RESULTS: Fifty-eight (60%) patients preferred to be
allocated to the exercise programme whilst 38 (39%) were indifferent; one patient
preferred conventional general practitioner (GP) management. No patient refused
randomisation. Comparing patients preferring the exercise programme with
indifferent patients showed that the former had a higher belief in the
effectiveness of the new treatment (P < 0.01), tended to have worse back pain (P
= 0.09), had back pain for a shorter duration (P = 0.04), and tended to have had
more GP home visits (P = 0.06). CONCLUSIONS: For many randomised trials
preference may be an important prognostic variable. In such circumstances,
preference should be taken into account in the final analysis. This study
demonstrates it is sometimes feasible to randomise patients to their less
preferred treatment, thus allowing more robust statistical comparisons between
randomised groups. This modification may make RCTs more rigorous and improve
their external validity.
PMID- 10180871
TI - Simulation models in the planning of health care facilities: an application in
the case of neonatal extracorporeal membrane oxygenation.
AB - OBJECTIVES: To investigate whether modelling techniques can be used in the
planning of health care facilities for patients requiring neonatal extracorporeal
membrane oxygenation (ECMO). METHODS: In a micro-simulation model the number of
patients that will have to be referred to facilities abroad is estimated for any
number of neonatal ECMO patients presenting annually for treatment in The
Netherlands, and any number of ECMO facilities. The inputs to the model consist
of the number of ECMO facilities, the number of patients presenting annually, the
duration of treatment and the date on which patients present for ECMO treatment.
The model is estimated on data from The Netherlands for 1992, during which 29
patients were treated in three facilities. Several future scenarios are modelled,
principally one in which a potential increase to 56 patients per year is
foreseen. RESULTS: The model indicates that, if such an increase takes place, no
additional ECMO facilities will be necessary in The Netherlands if between three
and four referrals annually to centres outside the region (or abroad) are
considered acceptable and feasible. In that situation, it is expected that on 22
occasions each year two patients will be treated simultaneously, for a total of
81 days. On ten occasions, all three facilities will be occupied at the same
time, for 21 days in total. On 199 days, at least one of the facilities will be
occupied. CONCLUSION: The current study shows that the acceptability and
feasibility of patient referrals to ECMO centres abroad is an important issue
which health care planners will have to consider. The study also shows that
modelling techniques can provide information that is useful to policy-makers in
the planning of health care facilities.
PMID- 10180873
TI - Comparison of doctors', nurses', politicians' and public attitudes to health care
priorities.
AB - OBJECTIVES: The aim of this study was to investigate differences in attitudes
concerning prioritisation in health care held by doctors, nurses, local
politicians and the general public. METHODS: Four groups were established: a
population sample of 2000 subjects, aged 18-70 years; a random sample of 1500
doctors of working age; a random sample of 1000 nurses of working age; and a
sample of 2200 politicians involved in health and social care administration,
mostly at the municipal level (altogether 6700 subjects). The main questionnaire
contained, among other things, a list of 12 statements concerning ethical
decisions regarding prioritisation in health care. Respondents were asked to
indicate their level of agreement with each statement. RESULTS: Most respondents
in all the groups felt able to express an opinion on the statements. Despite
considerable professional and cultural differences between groups, the views were
generally similar. On the whole, respondents supported liberal policies in which
the community took responsibility for subsidising health care. When differences
between groups occurred, it was usually the doctors who held discordant views.
Doctors were less inclined to consider a patient's economic status as a
determinant of priority for treatment than the other three groups. Both doctors
and nurses were less punitive towards patients with self-induced diseases. And
doctors and politicians were more likely to feel further cuts in health care
expenditure were possible than was true for nurses and the public. CONCLUSIONS:
While considerable uniformity of opinion exists on ethical issues of
prioritisation between the principal interested parties, the views of doctors
differ substantially on some matters. If prioritisation was left entirely to
doctors, health care provision would not reflect the views of other groups in
some important ways.
PMID- 10180872
TI - The cost-effectiveness of condoms in the prevention of HIV infection in England
and Wales: should condoms be available on prescription?
AB - OBJECTIVES: HIV and AIDS represent a considerable challenge to the British
National Health Service, and the resources devoted to treatment and prevention of
HIV/AIDS are significant and likely to increase. The focus of recent campaigns
promoting safer sexual practices to prevent the spread of HIV have focused on the
use of condoms, since condom use reduces the probability of infection.
Furthermore, it has also been suggested that condoms should be provided routinely
on prescription by general practitioners (GPs). The objective of this study was
to evaluate the cost-effectiveness of GP-provision of condoms in the prevention
of HIV infection. Since risk factors for HIV infection differ across population
groups, cost-effectiveness ratios for three at-risk groups were considered.
METHODS: Estimates of the cost per infection prevented and the cost per life year
gained were made for female heterosexuals, male heterosexuals, and male
homosexuals in England and Wales. Sensitivity analysis was conducted on a number
of key parameters. RESULTS: The costs per infection prevented were 2,327,744
Pounds for female heterosexuals, 9,709,987 Pounds for male heterosexuals and 1315
Pounds for male homosexuals. The corresponding costs per life year gained were
56,774 Pounds, 269,722 Pounds and 37 Pounds. When savings from the costs of care
were taken into account the use of condoms resulted in cost savings of nearly
50,000 Pounds for homosexual males. CONCLUSIONS: The provision of GP-prescribed
condoms is highly cost-effective for male homosexuals. Such provision is much
less cost-effective for heterosexuals, primarily due to the relatively low
prevalence of HIV in the heterosexual population and the low infectivity
parameter. This suggests that routine GP-provision of condoms would be
inappropriate for all at-risk groups, and should target high-risk groups,
specifically male homosexuals.
PMID- 10180874
TI - Costs and remuneration for cervical screening in general practice in the west of
Scotland.
AB - OBJECTIVES: To investigate associations between costs and remuneration for
cervical screening in general practice in relation to skill mix, features of
practice structure and deprivation levels in the local area; and, to identify
efficient policies for organising cervical screening in general practice. METHOD:
Questionnaire survey and interview study in 87 general practices in Greater
Glasgow Health Board an area in the west of Scotland which covers a socio
economically varied population. The main outcome measures were remuneration to
cost ratios (RCRs) for cervical screening and their natural logarithms (logRCRs).
RESULTS: Both the costs of cervical screening and RCRs varied widely between the
87 practices taking part. RCRs ranged from 0.29 to 14.67 (mean 2.64, median 2.18,
interquartile range 1.15-2.98). Twenty-one per cent (18) of practices earned less
than they spent on the organisation of screening, whilst 9% (8) of practices had
PCRs of more than 5:1. RCRs were significantly lower if medical staff were
involved in either taking smears or dealing with results. RCRs did not vary by
social deprivation score, despite uptake being lower in practices in more
deprived areas. This was explained by nurses working in practices in deprived
areas being more likely to take smears than nurses working in more affluent
areas. Sensitivity analyses were undertaken, altering key time and cost
assumptions. As a result, the absolute values of the RCRs changed, although the
overall pattern of association did not, with the exception of doctor involvement
in processing results which was no longer significant when average general
practitioners' income was substituted for locum rates. CONCLUSIONS: Practices in
deprived areas may be responding to greater pressure of work by making optimal
use of skill mix within the primary health care team. A more graduated incentive
payment scheme may more fairly reward practices in deprived areas which are less
likely to achieve 80% uptake due to relatively intractable features of practice
structure. Assuming that practice nurses provide an equivalent quality of service
to that provided by general practitioners, results suggest that doctor-nurse
substitution would be cost-effective for general practice based cervical
screening. Resource savings (principally doctor's time) could be redeployed to
other areas of primary health care.
PMID- 10180875
TI - The problem of 'noise' in monitoring patient-based outcomes: generic, disease
specific and site-specific instruments for total hip replacement.
AB - OBJECTIVES: To compare the performance of three types of patient-based health
status instrument--generic, disease-specific and site-specific--in assessing
changes resulting from total hip replacement (THR). METHODS: A two-stage
prospective study of patients undergoing surgery for THR involving an assessment
at a pre-surgical clinic and a follow-up clinic at 6 months. 173 patients with a
diagnosis of arthritis and being admitted for unilateral THR were recruited in
the outpatient departments of a specialist orthopaedic hospital and peripheral
clinics within Oxfordshire. Patients' health status was assessed using the 12
item Oxford Hip Score, the Arthritis Impact Measurement Scales (AIMS) and SF-36
general health questionnaire together with their surgeons' assessment using
Charnley hip score obtained before and 6 months after surgery. RESULTS: Effect
sizes, used to compare change scores, revealed that pain and function domains
changed most following THR on both the AIMS and the SF-36. 71 patients (41%) were
assessed as having symptoms or problems currently affecting lower limb joints
other than the hip recently replaced. Change scores were compared between these
patients and all other patients who reported no current problems with other
joints. The Oxford Hip Score found no significant difference between change
scores for these two groups of patients while both AIMS and SF-36 physical and
pain dimensions recorded significant differences of similar magnitude (physical P
< 0.01, pain P < 0.05). Likely reasons for this were apparent on closer
inspection of the item content of each instrument. CONCLUSIONS: Assessment of
outcomes in THR is necessarily long-term. Within studies of this kind, a hip
specific instrument (Oxford Hip Score) is likely to be more able to distinguish
between symptoms and functional impairment produced by the index joint, as
compared with other joints and conditions, than either a disease-specific
instrument (AIMS) or a generic health status measure (SF-36). This is important
given the high probability of existing and subsequent co-morbidity affecting such
populations of patients. This consideration is likely to be relevant to any long
term assessment programme following treatment for a condition which threatens
bilateral expression over time.
PMID- 10180876
TI - The cost and effectiveness of the London Helicopter Emergency Medical Service.
AB - OBJECTIVES: To assess the incremental consequences of the London Helicopter
Emergency Medical Service (HEMS) for the outcomes of survivors in terms of
disability and health status, and cost. METHODS: Prospective comparison of
outcomes in cohorts of seriously injured patients attended either by the HEMS or
by paramedically crewed land ambulances. In survivors, disability was assessed
using an 11-point disability scale, and general health status was measured by the
six dimensions of the 100-point Nottingham Health Profile (NHP) assessed 6 months
after the injury. Costs were estimated for the HEMS and associated facilities at
the Royal London Hospital, and the extra admissions attributable to the HEMS.
RESULTS: There was no evidence of reduced disability in HEMS survivors (estimate:
+0.8 disability grades worse; 95% CI: 0, 1.6), and no evidence of improvement in
the six NHP dimensions scores or in the mean number of problems with seven
aspects of daily living (estimated difference: +0.5; 95% CI: -0.2, 1.2). The
incremental costs of HEMS were estimated to be 2.0 Pounds million a year.
CONCLUSION: As there is no evidence of any improvement in outcomes overall for
the extra cost, the HEMS has not been found to be a cost-effective service.
PMID- 10180877
TI - Development standards for health measures.
AB - The growing demand for subjective measurements of health in clinical studies has
encouraged the rapid creation of many new scales, leading to compromises in the
quality of some instruments. Quality control standards are desirable to guide the
development of measures and subsequent data interpretation. The limitations in
existing measures may be classified under three broad topic areas: 1)
shortcomings in the design of the instrument, 2) methodological limitations in
the process of its development, and 3) shortcomings in the way that the
instrument is described following its initial development. We outline examples of
common problems in these areas and propose guidelines for the design, development
and presentation of health measurement methods. The guidelines represent a
preliminary step in formalizing a discipline of health measurement.
PMID- 10180878
TI - Software for analysing textual data.
PMID- 10180879
TI - Transactions cost economics and its applications to health services research.
PMID- 10180880
TI - Managing fund raising.
PMID- 10180881
TI - Make donor service excellence your top priority.
AB - Donor service excellence means putting the donor first at every level of fund
raising within your organization. It sounds simple, but it goes beyond building
donor loyalty and developing strong donor relations. It means caring about what
your donors desire and not just meeting fund-raising goals.
PMID- 10180882
TI - New attitudes and technologies make now the right time to create a "virtual"
association.
AB - The World Wide Web has become a convenient tool for research, communication, and
even commerce, but a recent survey of foundations and corporate giving programs
reveals that grant makers are not making full use of computer and Internet
capabilities that might benefit them.
PMID- 10180883
TI - Fund raising mentors: wisdom for winning.
AB - This article shares some of the most important lessons I have learned in 31 years
of marketing and fund-raising activities from five mentors. It also points out
the critical role that mentors play in one's career.
PMID- 10180884
TI - Powerful fund-raising letters--from A to Z. Part 3.
PMID- 10180885
TI - Sponsorship, or selling out??
PMID- 10180886
TI - Initial thoughts: international fund-raising consulting.
AB - There is a growing demand to secure private sector funding. Consequently, non
profit organizations in other countries need to create professional programs to
support their philanthropic needs.
PMID- 10180887
TI - When you are asked to give the sermon on the amount.
PMID- 10180888
TI - Data trends. DRG assignment patterns differ with hospital ownership.
PMID- 10180889
TI - The once and future healthcare crisis.
PMID- 10180890
TI - Medical intranet success factors.
PMID- 10180891
TI - IRS issues guidance on tax-exempt bond requirements.
AB - Enforcing compliance with rules governing facilities financed with tax-exempt
bonds recently has become an IRS priority. Integrated delivery systems (IDSs)
that include such facilities, therefore, should take steps to ensure that the
private business use of those facilities does not exceed the legal threshold
amount, thereby jeopardizing the tax-exempt status of the bonds. Management
contracts, research agreements, and leases are arrangements with the greatest
potential to result in noncompliance. Instituting a compliance program to monitor
the use of bond proceeds and minimize the amount of private business use of
facilities over the bond term can reduce an organization's risk of penalty.
PMID- 10180892
TI - Providing strategic financial leadership for integrated delivery systems.
AB - The increased complexity of financial and strategic decision making that
accompanies the formation of integrated delivery systems (IDSs) challenges CFOs
in these organizations to move beyond their traditional areas of responsibility.
System CFOs need to assume a strategic leadership role in IDSs by taking steps to
ensure that information required for high-level decision making is reliable,
accessible, relevant, and placed in a context that enhances its usefulness.
PMID- 10180893
TI - Market-stage analysis enhances strategic planning.
AB - Changing market conditions are challenging healthcare organizations to determine
how to allocate resources and make operational planning decisions to prepare for
future changes. A vital part of meeting these challenges is understanding the
impact of market stages, and using that knowledge to build effective business
strategies. Financial modeling that includes market-stage information provides
insight into market opportunities and presents a clearer picture of the
organizational changes that will need to be implemented at each stage. Effective
strategic action should take into account critical success factors in market
responsiveness, organizational responsiveness, operational effectiveness, and
financial strength.
PMID- 10180894
TI - Is your organization's market ready for a Medicare PSO?
AB - Provider organizations interested in forming a Medicare PSO should first
determine their market's readiness to accept a new Medicare risk product. How a
Market might receive a new Medicare PSO depends on numerous factors. These
factors include size and demographic characteristics of the Medicare Population;
capitation rate; level of commercial and Medicare managed care enrollment; market
concentration; provider supply, capabilities, and attitudes toward managed care;
and prevalence of large employers and their level of interest in Medicare risk
products.
PMID- 10180895
TI - Pay-for-performance compensation: moving beyond capitation.
AB - Although capitation has been instrumental in lowering healthcare costs, it also
has generated growing concern about quality of and access to healthcare services.
Shifting to pay-for-performance compensation programs, however, allows health
plans and physicians to balance economic incentives and operational outcomes,
which in turn encourages improved performance and benefits providers, payers, and
patients alike. A successful pay-for-performance program requires selection of
appropriate performance criteria, accurate assessment of the financial impact,
development of an effective means of communication between the health plan and
physicians, and gradual implementation of the plan.
PMID- 10180896
TI - Using real-estate-based financing to access capital.
AB - One strategy employed by healthcare organizations to increase their market
presence is the construction of new facilities. Accessing capital to fund such
construction, however, has become more of a challenge. One relatively untapped
source of building capital is real-estate-based financing. Nonrecourse mortgages,
turnkey net leases, and synthetic leases can provide several advantages to
healthcare organizations seeking capital, assuming issues related to building
ownership, debt and balance sheet effects, and tax-exempt status have been
thoroughly explored first.
PMID- 10180897
TI - Contingency arrangements do not necessarily equal fraud and abuse.
AB - Many healthcare organizations avoid entering contingency-based arrangements with
consulting firms that specialize in Medicare revenue optimization because they
fear Federal investigation of such an arrangement might lead to a finding of
fraud and abuse. A Medicare fraud alert issued by the HHS Office of the Inspector
General (OIG) appears to justify that fear, suggesting that contingency
arrangements are inherently unethical. Nonetheless, current Federal regulations
clearly allow healthcare organizations to enter into contingency-based
relationships with consulting firms to seek legitimate optimal payment.
Healthcare organizations may do so without fear of Federal legal action if they
ensure that the consultant is ethical and competent and that the DRG review
process used is both legitimate and retrospective, subjecting all recommended
changes to approval by both the healthcare organization and appropriate peer
review organization.
PMID- 10180898
TI - Value in health care: what providers and employers say.
AB - Earlier this year, two surveys were conducted among healthcare providers and
employers seeking their opinions regarding strategies they would employ to deal
with current and expected cost pressures of the healthcare marketplace as well as
healthcare value. The results of the surveys suggest that providers and employers
may not be seeing the issues the same way. Providers that partner with employers
will be the organizations best able to improve the quality of the care delivered-
and boost their competitive positions--while the employers will receive greater
value for their healthcare dollars.
PMID- 10180899
TI - The evolution of primary care networks.
AB - Many physician practices and primary care networks owned by hospital-based
healthcare systems have not been successful financially. By investing capital,
time, energy, and management expertise in these networks, however, systems can
dramatically improve their strategic advantage. A three-stage evolutionary
process that is necessary to achieve this strategic advantage comprises practice
acquisition, network development, and true integration. Although few primary care
networks run by hospitals or systems to date have reached stage three,
understanding the evolutionary process is a necessary first step toward success.
PMID- 10180900
TI - Designing an internal audit process for physician billing compliance.
AB - An internal audit process is central to an effective compliance program. When
based on pertinent Federal regulatory guidelines and executed by staff with
appropriate technical expertise, an internal audit limits opportunities for
noncompliant physician billing and reduces the risk of incurring financial
penalties. The design of an effective internal audit process will incorporate
uniform internal audit procedures, communication mechanisms, and educational
initiatives to correct any deficiencies that are identified. For healthcare
organizations that are involved with physician group practices, review of
physician documentation is particularly important. This review provides essential
information on potential areas of risk and offers a focus for future education of
physicians regarding appropriate billing and documentation.
PMID- 10180901
TI - Regional initiatives set the pace of EDI adoption.
PMID- 10180902
TI - HCFA issues administrative simplification proposed rules.
PMID- 10180903
TI - PFS compliance: achieving a learning culture.
PMID- 10180904
TI - CFO career ladder expands.
PMID- 10180905
TI - Health group responds to infant kidnapping in nearby hospital.
PMID- 10180906
TI - Security officers' people skills reduce problems at St. Luke's Hospital.
PMID- 10180907
TI - Malfunctioning security systems in Y2K.
PMID- 10180908
TI - An interview with: Tryst M. Anderson on providing security for hospital parking
facilities.
PMID- 10180909
TI - RF (radio frequency) system to monitor wandering patients ends alarm problem.
PMID- 10180910
TI - Med center combines security, patron service for its 42 parking areas.
PMID- 10180911
TI - Worst tornadoes in years: how hospitals fared; critical lessons learned.
AB - Tornado warnings have not been uncommon in many areas of the country this year
and when twisters touch down, they can be extremely deadly. When tornadoes swept
through Florida's Osceola County in late February, they caused 38 deaths and wide
spread damage. In April, tornadoes caused a number of deaths and considerable
damage in Nashville, TN; Birmingham, AL; and Gainesville, GA. Hospitals in those
areas that bore the brunt of treatment of victims activated disaster plans. This
report relates their experiences and the lessons learned from them.
PMID- 10180912
TI - Physician opportunity costs in physician practice cost functions.
AB - Estimation of cost functions for physician firms is problematic because many
physicians are self-employed, and the marginal opportunity cost of physician
labor is not observed. In this paper, we show how to recover marginal costs and
conventional measures of economies of scale from cost functions that condition on
the amount of physician labor input. In addition, we introduce the new concepts
of marginal nonphysician input costs and 'behavioral' economies of scale, which
reflect the structure of costs when physician labor input moves along a utility
maximizing expansion path. Our results could be useful in the design of resource
based physician fee schedules.
PMID- 10180913
TI - The demand for health with uncertainty and insurance.
AB - This paper develops Michael Grossman's demand-for-health model by letting the
depreciation rate depend upon the level of health, by letting the incidence and
size of illness be uncertain and by investigating how the individual's demand for
health would be affected by the introduction of insurance. Beside the more
theoretical results, there are also some results with important policy
implications. When formulating the hypothetical scenario in willingness to pay
(WTP) studies it is important whether the individual believes that the level of
health is uncertain or not. The existence of insurance could also affect the
stated WTP amount. Taking this into account could therefore explain some of the
differences in the WTP for seemingly identical health care programs in different
countries or different areas in the same country.
PMID- 10180914
TI - The effect of uncertainty on the demand for medical care, health capital and
wealth.
AB - We analyze the effect of the uncertainty of the incidence of illness on the
demand for medical care and on the accumulation of health capital and wealth over
the retirement years. We use a simplified version of a dynamic Grossman household
production model to characterize patterns of an individual's precautionary
behavior. Elderly individuals respond to uncertainty by smoothing their expected
utility over time by making specific patterns of purchases of medical care and
consumption. We examine these patterns for individuals with different degrees of
risk aversion.
PMID- 10180915
TI - Stochastic technology, production organization and costs.
AB - Using a model including patients, physicians, insurers and uncertain diagnostic
technology, the optimal cesarean rate is derived from preferences, technology and
the incidence rate, when the choice of insured patients is constrained only by
technology. Uncertain diagnosis produces unnecessary cesareans and unsafe vaginal
births. Technical progress can lead to more cesareans and higher costs. Joint
production of goods and bads and collective payments require incentive compatible
pricing schemes, different from RBRVS. Equilibrium outcomes of HMOs and free-for
service organizations are identical. However, implementable incentive schemes
involve additional costs. Efficiency requires insurers, and not providers, to be
liable for malpractice claims.
PMID- 10180916
TI - Evidence on the determinants of Canadian provincial government health
expenditures: 1965-1991.
AB - Real per capital provincial government expenditures on health care over the
period 1965-1991 are examined using pooled time-series cross-section regression
analysis: Key determinants of real per capita provincial government expenditures
on health care over the period 1965-1991 are real provincial per capita income,
the proportion of the provincial population over age 65 and real provincial per
capita federal transfer revenues. Established program financing had a negative
and significant impact on real per capita provincial government health
expenditures in Newfoundland and Quebec. An income elasticity of 0.77 implies
that health care is not a luxury good.
PMID- 10180917
TI - Phobic disorder, psychotherapy, and risk-taking: an economic perspective.
AB - Phobic disorders are receiving much attention in psychiatric practice today.
Agoraphobia, the most common of the phobic disorders, involves the risk of
experiencing a panic attack in public places, thus discouraging the worker from
fully participating in the labor market. This paper applies the economic tools of
rational choice under uncertainty to the analysis of agoraphobia, with the
purpose of gaining more insight as regards the extent of deviation from normal
work behavior (which presumably responds to incentives) and the effectiveness of
psychotherapy in treating work-avoidance, challenging the popular claim that the
cost of psychotherapy helps ensure its success.
PMID- 10180918
TI - Much ado about two: reconsidering retransformation and the two-part model in
health econometrics.
AB - In health economics applications involving outcomes (y) and covariates (x), it is
often the case that the central inferential problems of interest involve E[y/x]
and its associated partial effects or elasticities. Many such outcomes have two
fundamental statistical properties: y > or = 0; and the outcome y = 0 is observed
with sufficient frequency that the zeros cannot be ignored econometrically. This
paper (1) describes circumstances where the standard two-part model with
homoskedastic retransformation will fail to provide consistent inferences about
important policy parameters; and (2) demonstrates some alternative approaches
that are likely to prove helpful in applications.
PMID- 10180919
TI - The logged dependent variable, heteroscedasticity, and the retransformation
problem.
PMID- 10180920
TI - A model of the impact of reimbursement schemes on health plan choice.
AB - Flat capitation (uniform prospective payments) makes enrolling healthy enrollees
profitable to health plans. Plans with relatively generous benefits may attract
the sick and fail through a premium spiral. We simulate a model of idealized
managed competition to explore the effect on market performance of alternatives
to flat capitation such as severity-adjusted capitation and reduced supply-side
cost-sharing. In our model flat capitation causes severe market problems.
Severity adjustment and to a lesser extent reduced supply-side cost-sharing
improve market performance, but outcomes are efficient only in cases in which
people bear the marginal costs of their choices.
PMID- 10180921
TI - Why did the SSI-disabled program grow so much? Disentangling the effect of
Medicaid.
AB - The number of participants in the SSI program grew by 1.1 million from 1987 to
1993. This paper examines the role of Medicaid on the SSI participation decision.
I use the rapid growth in average Medicaid expenditure as a proxy for its value.
OLS estimates of Medicaid's effect may be biased because of omitted variables
bias and measurement error. I therefore apply two-stage least squares to estimate
Medicaid's effect, using average Medicaid expenditure for blind SSI recipients as
an instrument. These estimates show that rising Medicaid expenditure
significantly increased SSI participation among adults with low permanent
incomes, explaining 20% of the growth.
PMID- 10180922
TI - Medicaid managed care and infant health.
AB - This paper provides estimates of the effects of Medicaid managed care on prenatal
care adequacy and infant birthweights, using a census of 1994 Medicaid births in
Wisconsin, where some Medicaid recipients were enrolled in fully capitated health
maintenance organizations (HMOs) while others remained in traditional fee-for
service (FFS) systems. The results indicate that while Medicaid patients enrolled
in managed care programs may be more likely to receive adequate prenatal care,
birth outcomes under managed care are not significantly different from those
under FFS financing systems. We conclude that cost savings generated by Wisconsin
Medicaid managed care are not coming at the expense of maternity patients' or
infants' welfare.
PMID- 10180923
TI - Health care expenditures and GDP: panel data unit root test results.
AB - This short paper presents unit root test results for time series on per capita
national health care expenditures and gross domestic product in the OECD. Unlike
the country-by-country test used by [Hansen, P., King, A., 1996. The determinants
of health care expenditure: A cointegration approach. J. Health Econ, 15, 127
137], the test we employ exploits the panel nature of the OECD data. Using this
approach, we are able to reject the null hypothesis that these series contain
unit roots. No single test is likely to be definitive in this rapidly-evolving
area of econometric research; however, our results help to mitigate concern that
panel data analyses of national health care expenditures are misspecified.
PMID- 10180924
TI - Health care expenditure and GDP: panel data unit root test results.
PMID- 10180925
TI - Comparative dynamic analysis of the full Grossman model.
AB - The paper applies the method of comparative dynamic analysis to the full Grossman
model. For a particular class of solutions, it derives the equations implicitly
defining the complete trajectories of the endogenous variables. Relying on the
concept of Frisch decision functions, the impact of any parametric change on an
endogenous variable can be decomposed into a direct and an indirect effect. The
focus of the paper is on marginal changes in the rate of health capital
depreciation. It also analyses the impact of either initial financial wealth or
the initial stock of health capital. While the direction of most effects remains
ambiguous in the full model, the assumption of a zero consumption benefit of
health is sufficient to obtain a definite for any direct or indirect effect.
PMID- 10180927
TI - Alternative approaches to valuing intangible health losses: the evidence for
multiple sclerosis.
AB - This study uses both risk-risk and risk-dollar approaches to assess intangible
health losses associated with multiple sclerosis (MS). Using an estimation
approach that adjusts for potential perceptional biases that may effect the
expressed risk tradeoffs, we estimated parameters of the utility function of
persons with and without MS as well as the degree of subjects" overestimation of
the probability of obtaining MS. The sample included subjects from the general
population and persons with MS. We found that marginal utility of income is lower
in the state with MS than without it. However, the difference in marginal in two
states was greater for persons without MS than for those with the disease.
Persons with MS overestimated the probability of acquiring MS to a greater extent
than did persons within MS. Correcting for overestimation of this probability,
the value of intangible loss of a statistical case of MS derived from responses
of the general population was US$350,000 to US$500.000. Persons with MS were
willing to pay somewhat more than this (D80,118,J17).
PMID- 10180926
TI - The demand for cocaine by young adults: a rational addiction approach.
AB - This paper applies the rational addiction model to the demand for cocaine by
young adults in the Monitoring the Future panel. The price of cocaine is added to
this survey from the Drug Enforcement Administration's System to Retrieve
Information from Drug Evidence. Results suggest that annual participation and
frequency of use given participation are negatively related to the price of
cocaine. In addition, current participation (frequency) is positively related to
past and future participation (frequency). The long-run price elasticity of total
consumption (participation multiplied by frequency given participation) of -1.35
is substantial.
PMID- 10180928
TI - On optimal length of life.
PMID- 10180929
TI - Theological reflection in the supervision of pastoral care.
AB - Reviews some elements of group supervision in preparation for the ministry of
pastoral care and suggests five steps in theologically processing a case study.
Reflects on the Word of God as an interpretive resource to provide meaning to
life experiences. Suggests four ways demonstrating how the habit of an
interpretive approach and theological reflection can enrich the Christian
community.
PMID- 10180930
TI - Gerontology, spirituality, and religion.
AB - Traces the development of religious gerontology, particularly as it has moved
from its positivistic approach to its present phenomenological emphases. Opines
that religion reframes reality and therefore tends to reduce suffering. Claims
that to the extent one can reconcile one's self-definition with one's religious
worldview, anxiety levels will be determined.
PMID- 10180931
TI - L'Arche Daybreak: an example of interfaith ministry among people with
developmental disabilities.
AB - Describes pastoral support of a representational Jewish adult with a
developmental disability in a predominantly Christian setting, including Bat
Mitzvah preparation and celebration, and the resulting growth in self-esteem.
Outlines how this undertaking initiates a transformation into interfaith
awareness and appreciation in the author and in the surrounding Jewish and
Christian communities. Urges recognition of the gift of people with disabilities
to bring together others of varied religious traditions in mutual appreciation
and friendship.
PMID- 10180932
TI - Pastoral care for an unconscious person.
PMID- 10180933
TI - Doc-fee rules revisited. New regs shift less money to primary-care physicians.
PMID- 10180934
TI - Banned from the Internet. HCFA prohibits transfer of patient-identifiable data.
PMID- 10180935
TI - Catholic unity. Three orders are merging to create national system.
PMID- 10180936
TI - AHA recommends flexible ER policies.
PMID- 10180937
TI - IRS: where's the charity? Rural hospital manager may lose federal tax exemption.
AB - A rural hospital management company with ties to VHA may lose its federal tax
exemption because, according to the Internal Revenue Service, there's nothing
charitable about operating a hospital under contract. The case against the
company is significant because it calls into question the tax exemptions of any
not-for-profit corporation that manages or leases hospitals.
PMID- 10180938
TI - On the move again. Beverly to sell American Transitional Hospitals.
PMID- 10180939
TI - Fitting the bills. AMA: private contracting is out, patient protection and
tobacco control are in.
PMID- 10180940
TI - Values added. Corporate mission statements should be dusted off and used in
everyday decisions.
PMID- 10180941
TI - Bon Secours heads home. Catholic system forgoes national consolidation to focus
on assisted-living, nonacute care.
PMID- 10180942
TI - In the REIT direction. Integrated Health selling facilities to pay down debt.
PMID- 10180943
TI - Turning mortar into money. REIT is first to help not-for-profit systems
capitalize on their real estate holdings.
PMID- 10180944
TI - Justice Dept., HHS issue conflicting rules on False Claims Act.
PMID- 10180945
TI - Fraud-buster contract slated for 1999.
PMID- 10180946
TI - Spending estimates divide commission.
PMID- 10180947
TI - Exit from Medicare. Intermountain, PacifiCare drop risk plans in Utah.
PMID- 10180948
TI - AHA, nursing home group to collaborate.
PMID- 10180949
TI - Wheeling and dealing. Healthcare keeps up consolidation; docs lead pack.
PMID- 10180950
TI - Left at the altar. Speedy courtships spell disaster for some mergers.
PMID- 10180951
TI - Bringing law to Justice. Department's release of False Claims Act guidelines
boxes in hospital industry.
PMID- 10180952
TI - Out for blood. The newly overhauled American Red Cross is thirsty for a bigger
share of the $2 billion business of supplying blood to hospitals.
AB - The newly overhauled American Red Cross, led by President Elizabeth Dole (left),
has launched an ambitious campaign to increase its piece of the more than $2
billion business of supplying blood to hospitals. Its quest for market share has
sparked what some call a "blood war" with its main competitors: independent,
community-governed blood banks affiliated with America's Blood Centers.
PMID- 10180953
TI - VHA, White House launch quality programs.
PMID- 10180954
TI - Struggle in St. Louis. Medicare rollbacks cause providers to exit home care.
PMID- 10180955
TI - Going it together. Four Florida hospitals find success with direct-purchasing
cooperative.
PMID- 10180956
TI - First-quarter turnaround. Industry makes gains; providers group still trails.
PMID- 10180957
TI - 16 senior executives acquire Hunter Group.
PMID- 10180958
TI - Putting teeth into policy. AHA asks how to handle members that commit fraud.
PMID- 10180959
TI - Computer systems: are ORs getting what they need?
PMID- 10180960
TI - Study documents savings from total knee pathway.
PMID- 10180961
TI - More is needed from OR info systems.
PMID- 10180962
TI - Getting an info system that will work.
PMID- 10180963
TI - Benchmarks. Wide variation in draping.
PMID- 10180965
TI - 'Corporate soul' engages worker passion.
PMID- 10180964
TI - OR costing and an MD 'report card'.
PMID- 10180966
TI - CDC updates guideline on surgical site infection.
PMID- 10180967
TI - HCFA releases proposed practice expense RVUs.
PMID- 10180968
TI - Creating a data warehouse for business analysis.
PMID- 10180969
TI - Physician acceptance of new medical information systems: the field of dreams.
AB - Physicians often fail to embrace a complex information system, may not see its
relevance to their practices, and are characteristically reluctant to invest the
time and energy to be trained in its use. Why is widespread physician buy-in so
difficult to achieve? From physicians overwhelmed with change to failing to begin
with an adequate physician base of support, this article explores some of the
reasons that physicians demonstrate little buy-in to this process and offers
suggestions to help create a more successful implementation. Ways to build
acceptance include acknowledging the importance of physicians as customers and
training them early and often.
PMID- 10180970
TI - The electronic medical record system: health care marvel or morass?
AB - The author considers the potential advantages and disadvantages, as well as
possible unintended consequences, of introducing electronic medical record
systems in health care organizations. Special consideration is given to the
issues such information systems raise concerning privacy, confidentiality, and
quality of care from both patient and provider perspectives. The potential gains
from computerizing medical records include the benefit of instantaneous
availability of patients' medical history, treatment regimes, and current health
status in routine and emergency clinical situations. Ease of access to this
information should reduce adverse outcomes. The added value of a complete and up
to-date medical record immediately available to medical caregivers seems
undeniable. The potential disadvantages include issues around patient
confidentiality and unauthorized access to records, the enormous capital
investment for computer hardware, and system maintenance.
PMID- 10180971
TI - Security and confidentiality of health information systems: implications for
physicians.
AB - Adopting and developing the new generation of information systems will be
essential to remain competitive in a quality conscious health care environment.
These systems enable physicians to document patient encounters and aggregate the
information from the population they treat, while capturing detailed data on
chronic medical conditions, medications, treatment plans, risk factors, severity
of conditions, and health care resource utilization and management. Today, the
knowledge-based information systems should offer instant, around-the-clock access
for the provider, support simple order entry, facilitate data capture and
retrieval, and provide eligibility verification, electronic authentication,
prescription writing, security, and reporting that benchmarks outcomes management
based upon clinical/financial decisions and treatment plans. It is an integral
part of any information system to incorporate and integrate transactional
(financial/administrative) information, as well as analytical (clinical/medical)
data in a user-friendly, readily accessible, and secure form. This article
explores the technical, financial, logistical, and behavioral obstacles on the
way to the Promised Land.
PMID- 10180972
TI - An information system model for negotiating capitation contracts.
AB - Capitation contracts require health care organizations to negotiate on a much
more sophisticated and risky level. Understanding whether a capitation contract
will allow a hospital to remain financially viable while providing quality care
requires estimating the number of patients to be served, the amount and types of
services to be offered, and the cost to provide them. This article presents an
information system model designed to assist a large hospital, not only in
determining true patient cost, but also in aggregating the cost information in
different ways, such as conducting a case-mix analysis, to perform a more
informed quote analysis for capitated contracts.
PMID- 10180973
TI - The use of imperfect data in managed care organizations.
AB - Two critical milestones appear to be occurring in the development of medical
groups moving to improve medical care effectiveness. These include the abilities
to work with imperfect and unflattering data. There is a clear linkage between
these two concepts, because forward clinical improvement or business planning is
often delayed as individual physicians seek to await "perfect data" when
confronted with unflattering information. In the form of "profiles" in
particular, providers often react negatively, with complaints that the
information is "imperfect" or that it fails to capture some nuance of their
sicker or unique patient populations. The translation of imperfect information to
effective clinical practice anyway remains a success fundamental to managing
highly competitive medical groups and health plans. It is centrally dependent on
the understanding, use, and application of "imperfect data".
PMID- 10180974
TI - Value-based health care, Part 2. The physician imperative: define, measure, and
improve health care quality.
AB - Health care is the only major industry that lacks agreed-upon metrics to
objectively define the quality of its products and services. The fundamental
deficiency has led to the use of price as the de facto metric for patient
contracting. Provider selection defaults to price because quality is assumed to
be equal across all physicians and hospitals. This assumption is erroneous and
now obsolete. Health care quality can be accurately measured using sophisticated
illness modeling techniques that objectively risk-adjust patients level data.
Providers' clinical data can be correlated with patient self-assessed outcomes
for all episodes of inpatient and outpatient care. Physicians and their hospitals
currently managing financial risks and those positioning themselves for these
opportunities find such tools and techniques to be invaluable. Credible
information creates a power shift away from price-based contracting to a true
competitive marketplace that rewards quality of care. Purchasers and patients
seek providers who objectively demonstrate their value on both quality and price.
Part I of this article appeared in the January/February issue of The Physician
Executive.
PMID- 10180975
TI - Finding the essential difference.
AB - The idea of what is essential and what is peripheral is basic to all intelligent
management of change. At the core of all our resistance to change is the fear
that we will lose something of ourselves, something unrecoverable. "Touching
ground"--gaining clarity on what we are truly about, and shaping our strategies
around that core--is a key skill of the change master. What is the most important
element in helping people deal with change? According to Roger Fritz, President
of Leadership by Design, Inc., a St. Louis consulting firm, "Helping them
recognize what's essential. There are two kinds of change: Technical change and
profound change. A technical change asks you to learn something different. A
profound change ask you to be someone different." Too often, we confuse the two
and are met with resistance.
PMID- 10180976
TI - Who gets fired in a tight job market?
AB - One of the peculiarities of the health care workplace right now is that while
organizations are frantic to hire, they are also quicker to fire. Judging from
surveys and reports from headhunters, it's obvious there are some new reasons why
-and when--people get fired. The most common cause for firing is the inability to
meet the boss's expectations. Three, often-documented, reasons for severance are
examined: (1) not being able to produce what's needed with the culture; (2)
lacking the level of technical skills required; and (3) not being emotionally
committed to the role the candidate was hired to play. What can you do to protect
yourself? Do your homework. Don't fall into the trap of being taken in by an over
eager hirer or by the prospect of making an inordinate difference.
PMID- 10180977
TI - Health care futures, Part 1. The emergence of the new health care consumer. Panel
discussion.
AB - In Part 1 of this second annual panel discussion, six experts examine the new
health care consumer. The whole concept of the patient as consumer still makes
people uneasy when it's applied to health care. Whether you prefer consumer,
customer, purchaser, end-user, ultimate buyer, or beneficiary, one thing's for
sure: Many of us are as different from the bygone patient as an HMO is from the
general practitioner who made house calls. One of the reasons for many Americans'
new interest, knowledge, attitudes, and expectations about health and health care
is the Internet, the second topic in this discussion. In Part 2, physician
executives from the three leading physician practice management companies (PPMCs)
join Jeff Goldsmith, Barbara LeTourneau, and Uwe Reinhardt for a spirited
exchange about this burgeoning new industry in the American health care sector.
They will tackle questions such as: Are PPMCs delivering what they promise? What
will separate successful PPMCs from the rest? Can PPMCs meet Wall Street's
earnings expectations and also help physicians deliver better care? When PPMCs
win, who loses? And, what roles will physician executives play in PPMCs?
PMID- 10180978
TI - What to do next.
AB - Why do we work? While there may be some obvious, practical answers to this
question, like needing to make money to survive, there are other reasons that
people work. These include working: to have stimulation and excitement--to meet
new challenges and have variety in your life; for love and affection--to be with
colleagues, clients, customers and to provide security and protection for family
and friends; and to leave a thumbprint on the world and change individuals,
systems, and institutions. For quality life, it is necessary not only to work but
to enjoy your work. For physicians considering careers in medical management, the
key to success is being truly excited about management activities. If you are
heading towards management, you need to view some of the tasks as fun or you
probably won't stay with it very long.
PMID- 10180979
TI - When it's time to say goodbye.
AB - You've landed the perfect job, but now you must face your current employer and
deliver the news that you're leaving the organization. While an exciting time,
this can also certainly be a stressful one. Here are some strategies and ideas
for saying goodbye to an employer that may be useful in guiding your actions.
From being ready for counter-offers to downright hostility, you need to be
prepared to deal with various scenarios. No matter how you have steeled yourself
to go into the boss's office to share your news, you cannot predict with total
accuracy just what his or her response will be. There will always be surprises,
although usually things are never as bad as your imagined worst-case scenario.
However, when you are ready to make your plans known, one simple rule is always
required: You must have total commitment to your new position.
PMID- 10180980
TI - The future of managed care: the debate continues.
AB - The Patient Access to Affordable Care Act has acted as a catalyst in the health
care debate over the future of managed care. The Employee Retirement Income
Security Act, once a sacred cow, is now under intense scrutiny. Congress is
laying the ground work to create consumer protections in health care, but time in
this legislative session may run out. If Congress acts this year, there could be
a fundamental shift in the control over health care.
PMID- 10180981
TI - 3-D CT angio might give PACS a jump start.
PMID- 10180982
TI - Mammography improves under MQSA oversight.
PMID- 10180983
TI - Interventional radiology steps in for emergencies.
PMID- 10180984
TI - Surviving capitation via utilization management.
PMID- 10180985
TI - Oncology and therapy boost nuclear medicine.
PMID- 10180986
TI - Lymphatic mapping aids staging of melanoma.
PMID- 10180987
TI - FDG imaging without PET.
PMID- 10180988
TI - Cardiac group develops digital cath network.
PMID- 10180989
TI - Nuclear exam rivals venography for clots.
PMID- 10180990
TI - Role of core biopsy system for breast remains uncertain.
PMID- 10180991
TI - Ultrasound accreditation raising quality standards.
PMID- 10180992
TI - MRI assumes high-profile role in diagnosis of MS.
PMID- 10180993
TI - 3-D ultrasound: will it become a clinical tool?
PMID- 10180994
TI - Lumbar spine pain often an MRI waiting game.
PMID- 10180995
TI - Roots and riches tempt Asians back to the fold.
PMID- 10180996
TI - Data show filmless imaging saves in high-volume setting.
PMID- 10180997
TI - St. John's Wort for depressive disorders: results of an outpatient study with the
Hypericum preparation HYP 811.
AB - The efficacy and tolerability of a high-dose formulation of St. John's Wort
extract, HYP 811, was tested in 607 patients in a 6-week, prospective,
multicenter, postmarketing surveillance study. Severity of depression was
assessed by physicians using the Hamilton Depression Scale; patient self
evaluation was performed using the von Zerssen Depression Scale. After 6 weeks of
treatment, both scores improved by approximately 60%, on average. Disturbances in
well-being, such as dejection, loss of interest, and generalized physical
complaints, diminished during therapy. The tolerability of HYP 811 was rated
"very good" and "good" in 89.4% of cases. After 3 weeks of treatment, dosage in
128 patients (21.1%) was successfully reduced to one capsule daily.
PMID- 10180998
TI - Phytochemical characterization of various St. John's Wort extracts.
AB - Hypericum perforatum is used for its beneficial effects on the nervous system,
especially as an antidepressant. Owing to the fast-growing St. John's Wort market
in the United States, more and more products (herb and extract) are sold at
different quality levels. The amount of well-dried H. perforatum plant material
is limited and other species with differing composition and no proof of efficacy
are sold. The generally used method for standardization--spectrophotometric
determination of naphthodianthrones--is not as selective as a high-performance
liquid chromatographic (HPLC) method and can be manipulated (eg, by adding
colorants). The different analytical methods used for characterization of St.
John's Wort are discussed and a combined spectrophotometric and HPLC method is
proposed. Qualitative and quantitative ranges for pharmaceutically relevant
compounds of St. John's Wort extracts are cited and the composition of European,
US, and Far East extracts is detailed. The influence of the production process,
which involves extraction solvents, on phytochemical composition is also
described.
PMID- 10180999
TI - Evaluating test performance criteria: concepts and practices.
PMID- 10181000
TI - A new spin on cytocentrifugation.
AB - The patented Cytopro system design makes significant advances in the convenience
and reliability of cytocentrifugation. The chamber and pad are designed to
facilitate prewetting and to better control fluid flow rates. The sealed rotor is
durable, convenient, and reliable with significant patented features impacting
sample quality and convenience of operation.
PMID- 10181001
TI - Comparing the performance of automated diluters with the accuracy standards for
class A volumetric glassware.
PMID- 10181002
TI - Breath tests: a potential noninvasive method for the early diagnosis of cancers
and other disorders.
PMID- 10181003
TI - The power of consolidation: a case study.
PMID- 10181004
TI - Determination of the anti-Alzheimer's disease drugs tacrine, 7-methoxytacrine,
and its metabolites by capillary zone electrophoresis.
PMID- 10181005
TI - Mobile storage applications in clinical laboratory operations.
PMID- 10181006
TI - Platelet-rich plasmapheresis: a meta-analysis of clinical outcomes and costs.
AB - Platelet-rich plasmapheresis (PRP) just prior to cardiopulmonary bypass (CPB)
surgery is used to improve post CPB hemostasis and to minimize the risks
associated with exposure to allogeneic blood and its components. Meta-analysis
examines evidence of PRP's impact on clinical outcomes by integrating the results
across published research studies. Data on clinical outcomes was collected from
20 published studies. These outcomes, DRG payment rates, and current national
average costs were used to examine the impact of PRP on costs. This study
provides evidence that the use of PRP results in improved clinical outcomes when
compared to the identical control groups not receiving PRP. These improved
clinical outcomes result in subsequent lower costs per patient in the PRP groups.
All clinical outcomes analyzed were improved: blood product usage, length of
stay, intensive care stay, time to extubation, incidence of cardiovascular
accident, and incidence of reoperation. The most striking differences occur in
use of all blood products, particularly packed red blood cells. This study
provides an example of how initial expenditure on technology used during CPB
results in overall cost savings. Estimated cost savings range from $2,505.00 to
$4,209.00. More importantly, patients benefit from improved clinical outcomes.
PMID- 10181007
TI - Perfusion services national process improvement benchmarking.
AB - The Joint Commission on Accreditation of Health Care Organizations recommends
national and regional benchmarking in the quality improvement process.
Benchmarking is comparing your organization's patient care process outcomes to
the best. This communication describes a national benchmarking process for peer
comparison of indicators in perfusion patient services process improvement. A
databasing communication aplet was designed to facilitate national benchmarking
as part of a larger perfusion service management software application. When
patient information is entered in the patient database post precedure, patient
specific numeric data and 'yes'/'no' queries are entered at the clinical site. At
any time, the local perfusionist system manager may transmit their own data and
receive national database group results by modem and a 1-800 phone number. Local
indicator outcomes are compared to national results. Strategies are employed to
assure that institution and patient name remain anonymous and institution
specific data are stored at the clinical site. Participating institutions employ
an e-mail aplet to discuss and decide which indicators to employ as a group. Nine
institutions have contributed outcome data for more than 6,425 cardiopulmonary
bypass (CPB) procedures to a national database for ten months. National and
institutional means for six discrete CPB outcome parameters are compared. The
percent 'yes' responses to four procedure-related questions are compared. Joint
Commission recommended benchmarking is accomplished while patient care is
improved by comparing outcomes.
PMID- 10181008
TI - Fiber manufacturing, membrane classification, and winding technologies associated
with membrane oxygenators.
AB - Fiber bundling refers to the process of winding hollow polypropylene fibers onto
the central core of a membrane oxygenator. Identifying the various bundling
techniques serves to facilitate the clinician's understanding of unique device
characteristics and the subsequent manufacturing process. This technical
information has been voluntarily provided by the product managers and engineers
of current membrane manufacturers. Currently the industry employs four primary
bundling techniques: single strand, mat configuration, tape and helical. Single
strand wraps one fiber at a time, up and down a central core to create the fiber
bundle. A modification of the single strand technique is the single strand multi
toe, where multiple fibers are wound at a time. Mat technology wraps a large,
woven sheet consisting of uniformly placed fibers and spacing filaments, around
the oxygenator core. A modification is the double mat, where two sheets of fibers
oriented at a specific bias to each other, are wrapped to yield a fiber bundle.
Tape technology involves evenly spaced fibers, 5 to 10 fibers wide, wrapped up
and down the length of the core. Helical utilizes a spacing filament that is
spiraled around each individual fiber and then around the core of the device.
PMID- 10181009
TI - Evolution of a cardiovascular information system.
AB - The competitive nature of our evolving health care system mandates a concomitant
increase in the level of sophistication of the cardiovascular information system.
The new paradigms in health care also mandate a re-engineering of the process of
data collection and analysis. This paper deals with a variety of hardware,
software, and human issues encountered at our institution. Topics covered include
implementation of service line management, utilization of an interdisciplinary
medical informatics model, database conversion, and application development.
Special attention will be paid to the development of a system which is a
comprehensive information system for clinical and financial management of the
cardiovascular patient, not just a quality-of-care database.
PMID- 10181010
TI - What is the most accurate, cost-effective way to diagnose acute viral hepatitis?
PMID- 10181011
TI - Use of antioxidants in the prevention and treatment of disease.
AB - Considerable interest has risen in the idea that oxidative stress is instrumental
in the etiology of numerous human diseases. Oxidative stress can arise through
the increased production of reactive oxygen species (ROS) and/or because of a
deficiency of antioxidant defenses. Antioxidant deficiencies can develop as a
result of decreased antioxidant intake (such as vitamins C and E), synthesis of
enzymes (such as superoxide dismutase and glutathione peroxidase) or increased
antioxidant utilization. Insufficient antioxidant enzyme synthesis may in turn be
due to decreased micronutrient availability (such as selenium, magnese, copper
and zinc). Of those diseases linked with oxidative stress, cardiovascular disease
provides the strongest evidence for the protective role of antioxidants. A high
consumption of fruit and vegetables, which are good sources of antioxidants, is
associated with a lower coronary risk. More specifically, there is evidence of a
reduced coronary risk in populations with high blood levels of the antioxidant
nutrients, vitamins C and E. Evidence is also accumulating that diabetes, and
microvascular complications associated with diabetes, involve oxidative stress
and have compromised antioxidant status. In addition, patients who develop acute
respiratory distress syndrome (ARDS) also exhibit clear evidence of oxidative
stress. Definitive proof for active oxygen formation and oxidative cell damage
being causative rather than a result of other underlying these pathologies
remains elusive; however, evidence is sufficiently compelling to suggest that
antioxidants are potential therapeutic agents in the above conditions.
PMID- 10181012
TI - Aging and oxidative stress.
AB - Aging is the accumulation of changes that increase the risk of death. Aging
changes can be attributed to development, genetic defects, the environment,
disease, and the inborn aging process. The latter is the major risk factor for
disease and death after age 28 in the developed countries. In these countries,
average life expectancies at birth (ALE-B) now range from 76-79 years, 6-9 years
less than the limit of about 85 years imposed by aging. Aging changes may be
caused by free radical reactions. The extensive studies based on this possibility
show promise of increasing the ALE-B to 85 years and beyond.
PMID- 10181013
TI - Magnetic resonance spectroscopy in clinical chemistry: the present and the
future.
AB - Magnetic resonance spectroscopy is a powerful technique for the analysis of
complex mixtures. Up to now, little of its potential in everyday clinical
chemistry has been realized. An overview of the fundamentals, a discussion of the
technology, and some outstanding examples of the clinical chemical research are
presented. Clinical chemists are encouraged to seek out and apply this
methodology to problems for which it is well suited.
PMID- 10181014
TI - Nursing, health education and health promotion: lessons learned, progress made
and challenges ahead.
PMID- 10181015
TI - Understanding binge drinking among young people: an application of the Theory of
Planned Behaviour.
AB - Binge drinking (i.e. consuming half the recommended weekly consumption of alcohol
in a single session) is a common activity among young people. Using the Theory of
Planned Behaviour as its theoretical framework, this paper reports a study
exploring the motivational and attitudinal factors underlying binge drinking in a
sample of undergraduate students. Questionnaires were completed by 136
undergraduates which focused on their drinking behaviour and their beliefs about
binge drinking. Binge drinking was found to be more prevalent among male
respondents, and a number of significant differences in the beliefs of male and
female respondents were found which supported this difference in drinking
behaviour. A regression analysis identified two key predictors of the frequency
of binge drinking; these being positive control beliefs and perceived behavioural
control. Frequent binge drinkers were more likely to recognize the influence of a
range of factors which may serve to encourage binge drinking (e.g. celebrating an
event) and less likely to believe that the decision to engage in binge drinking
is under their control. The results are discussed in relation to measures which
may help to reduce the incidence of binge drinking through changes in the social
environment.
PMID- 10181016
TI - Interpretations of healthy and unhealthy eating, and implications for dietary
change.
AB - Central to many considerations of health-related dietary change is the
interpretation given to 'healthy' and 'unhealthy' eating. Results are reported
from two studies which investigated people's understanding of these concepts. The
first study involved structured interviews with 48 respondents: a wide range of
interpretations of healthy and unhealthy eating was found using content analysis
techniques. The second study (n = 242) used questionnaires to assess the extent
to which different interpretations were endorsed. The extent to which different
eating behaviours were perceived as healthy or unhealthy varied greatly. A
principal components analysis of perceptions of healthy and unhealthy eating
produced five separate factors. Some differences in perceptions were found for
people of different age, gender and educational level. Objectively assessed
dietary intake and perceived intake were found to be two distinct quantities.
'Healthy' eaters were found to perceive 'healthy eating' slightly differently to
'unhealthy' eaters. The results suggest that lay understanding of healthy eating
does generally conform with dietary guidelines, and therefore health promotion
priorities should focus on physical and psychological constraints to healthy
eating, rather than attempting to increase the public's knowledge as a whole.
PMID- 10181017
TI - Health promotion: perceptions of Project 2000 educated nurses.
AB - The new approach to pre-registration nursing education in the UK (Project 2000)
has an overt health focus as well as a specific remit to prepare nurses for a
role as promoters of health. Data reported in this paper illuminate Project 2000
students' understanding of the concepts of health promotion and health education,
and indicate the extent to which qualified nurses who have completed this new
Project 2000 programme perceive themselves to be prepared for a health promotion
role. Findings indicate that students are confused about the terms health
education and health promotion, although most feel there is a distinction between
the two. Students' descriptions emphasize individualistic approaches, and
lifestyle and behaviour changes. Many recognize that health promotion should have
a broader application and demonstrate a sophisticated grasp of the philosophy
underpinning the promotion of health through their general perceptions of
nursing. This understanding is not labelled health education or health promotion,
but is embedded in their articulation of concepts such as holism, patient-centred
care and enhancing independence. Paradoxically, both students and Project 2000
qualified nurses (diplomates) illustrate a clear grasp of the more complex issues
surrounding the concept of health promotion while remaining confused by the
terminology and its relationship to practice.
PMID- 10181018
TI - Computerized tailored feedback to change cognitive determinants of smoking: a
Dutch field experiment.
AB - In the last decade, attempts have been made to improve the efficacy of minimal
interventions by tailoring them to individual features. In the development of
these tailored interventions, it is important to know which information in
interventions is essential. Most smoking cessation interventions contain
information on the outcomes of quitting and skills to be used in a quit attempt.
The present study was designed to assess the cognitive changes caused by both
sorts of information. Therefore, 246 smokers who were planning to quit within 6
months were randomly assigned to three different conditions. In the first
condition, the respondents received a computer-generated tailored letter on the
outcomes of smoking cessation. In the second condition, the respondents received
a computer-generated tailored letter containing self-efficacy enhancing
information, mainly on skills. In both conditions, the contents of the letters
were based on the pre-test scores of the participants. Participants in the
control condition did not receive any cessation information. The results show
that information on the outcomes of quitting changed expected outcomes while
information on coping skills changed self-efficacy expectations, in comparison
with the control condition. Comparing both experimental conditions, information
on the outcomes led to changes in expected outcomes, whereas information on
coping skills did not lead to higher self-efficacy expectations than information
on the outcomes of quitting. It is concluded that the hypothesized effects were
partly verified.
PMID- 10181019
TI - Long-term effectiveness of computer-generated tailored feedback in smoking
cessation.
AB - Although tailored interventions consisting of only a few pages of information
lead to more quitting than no intervention in the short term, the long-term
efficacy of a single tailored intervention still has to be proven. In the present
study smokers were reactively recruited and randomly allocated to one of four
intervention conditions: (1) outcome information, (2) self-efficacy enhancing
information, (3) both sorts of information or (4) no information. Smokers in the
three experimental groups received computer-generated tailored feedback
containing the condition-specific information, by mail. The results from the 14
months follow-up can be summarized as follows. Compared to the no information
condition, all three experimental conditions led to significantly more smokers
who had engaged in 24-h quit attempts. However, no experimental condition led to
more 7-day quitting than the no information condition. With regard to continuous
abstinence, the experimental condition offering a combination of outcome
information and self-efficacy enhancing information had a significant effect,
compared to the no information condition. It is concluded that a minimal six-page
tailored intervention can be beneficial in supporting smokers to quit smoking,
even after 14 months.
PMID- 10181020
TI - Effects of a school-based smoking prevention program among subgroups of
adolescents.
AB - In autumn 1995 The Norwegian Cancer Society in cooperation with The Research
Center for Health Promotion, University of Bergen started a study of school-based
interventions aiming at preventing smoking among pupils in Norwegian secondary
schools. The study comprised a nationwide sample of 4441 students at 99 schools
(195 classes). This panel of students is followed through annual data collections
till they graduate in spring 1997. Written consensus from students and parents
was obtained from 95%. Schools were systematically allocated to one of four
groups: Group A, control; Group B, intervention, containing classroom program,
involvement of parents and teacher courses; Group C, like B, but without teacher
courses; Group D, like B, but without parental involvement. Baseline data were
collected by questionnaires administered in class in November 1994 and the first
follow-up survey was carried out in May 1995. At follow-up the proportion of
smokers had increased by 8.3 percentage points in Group A (control) and by 1.9
percentage points in Group B (most extensive intervention). As expected, the
recruitment of smokers was higher in Groups C and D than in the ideal
intervention, but lower than in the control group. Effects of the most extensive
program among subgroups of students were examined by comparing Groups A and B.
Students are categorized as high risk or low risk based on scores on scales
measuring sensation seeking, physical maturity, antisocial behavior and parental
smoking. The effect of the program on recruitment of smokers seems to have been
at least as strong or even stronger among 'high-risk' students than among other
students.
PMID- 10181021
TI - A multiple case study of implementation in 10 local Project ASSIST coalitions in
North Carolina.
AB - Community health promotion relies heavily on coalitions to address a multitude of
public health issues. In spite of their widespread use, there have been very few
studies of coalitions at various stages of coalition development. The purpose of
this study was to identify factors that facilitated or impeded coalition
effectiveness in the implementation stage of coalition development. The research
design was a multiple case study with cross-case comparisons. Each of the 10
local North Carolina Project ASSIST coalitions constituted a case. Data
collection included: semi-structured interviews, observation, document review,
and surveys of members and staff. Some of the major factors that facilitated
implementation included: the ability of the coalition to provide its own vision,
staff with the skills and time to work with the coalition, frequent and
productive communication, cohesion or a sense of belonging on the coalition, and
complexity of the coalition structure during the intervention phase. Barriers to
effective implementation included: staff turnover and staff lacking community
organization skills, dependence on the state-level staff during the planning
phase and lack of member input into the action plan. Conflict contributed to
staff turnover, reluctance to conduct certain activities and difficulty in
recruiting members, all of which had implications for implementation.
PMID- 10181022
TI - How best to measure implementation of school health curricula: a comparison of
three measures.
AB - The impact of school health education programs is often attenuated by inadequate
teacher implementation. Using data from a school-based nutrition education
program delivered in a sample of fifth graders, this study examines the
discriminant and predictive validity of three measures of curriculum
implementation: class-room observation of fidelity, and two measures of
completeness, teacher self-report questionnaire and post-implementation
interview. A fourth measure, obtained during teacher observations, that assessed
student and teacher interaction and student receptivity to the curriculum
(labeled Rapport) was also obtained. Predictive validity was determined by
examining the association of implementation measures with three study outcomes;
health knowledge, asking behaviors related to fruit and vegetables, and fruit and
vegetable intake, assessed by 7-day diary. Of the 37 teachers observed, 21 were
observed for two sessions and 16 were observed once. Implementation measures were
moderately correlated, an indication of discriminant validity. Predictive
validity analyses indicated that the observed fidelity, Rapport and interview
measures were significantly correlated with post-test student knowledge. The
association between health knowledge and observed fidelity (based on dual
observation only), Rapport and interview measures remained significant after
adjustment for pre-test knowledge values. None of the implementation variables
were significantly associated with student fruit and vegetable intake or asking
behaviors controlling for pre-test values. These results indicate that the
teacher self-report questionnaire was not a valid measure of implementation
completeness in this study. Post-implementation completeness interviews and dual
observations of fidelity and Rapport appear to be more valid, and largely
independent methods of implementation assessment.
PMID- 10181024
TI - Using condom data to assess the impact of HIV/AIDS preventive interventions.
AB - The effective evaluation of preventive activities depends on the identification
of indicators and the selection of appropriate outcome measures which reflect the
goals of the intervention. An increase in condom use has been seen as a positive
sign of the impact of HIV/AIDS public education. This paper examines possible
sources of data relating to condom use in the context of assessing public
response to the AIDS epidemic, with particular reference to methodological
challenges presented by each; issues relating to the validity of data, problems
of interpretation and the scope for improvement. A multiple indicator approach,
using several types of data in unison, is advocated. Conclusions drawn from the
multiple indicator approach are likely to be firmer and sounder than those drawn
from the single indicator approach, and are more likely to offer insight into the
mechanisms which influence particular outcomes.
PMID- 10181023
TI - Formative research in a school-based obesity prevention program for Native
American school children (Pathways).
AB - This paper describes how formative research was developed and implemented to
produce obesity prevention interventions among school children in six different
Native American nations that are part of the Pathways study. The formative
assessment work presented here was unique in several ways: (1) it represents the
first time formative research methods have been applied across multiple Native
American tribes; (2) it is holistic, including data collection from parents,
children, teachers, administrators and community leaders; and (3) it was
developed by a multi-disciplinary group, including substantial input from Native
American collaborators. The paper describes the process of developing the
different units of the protocol, how data collection was implemented and how
analyses were structured around the identification of risk behaviors. An emphasis
is placed on describing which units of the formative assessment protocol were
most effective and which were less effective.
PMID- 10181025
TI - Evaluation of the Norwegian campaign against the illegal spirits trade.
AB - In 1993, a 21m NOK (3m US$) national campaign against trade with illegal spirits
(homebrewed or smuggled) was launched in Norway. This article reports results of
its evaluation study. Surveys covering the age range 16-80 were carried out just
before the campaign started and 1 year later. Half of those responding at
baseline as well as a new sample were surveyed after 1 year. While at baseline
48% reported to have drunk and 16% to have bought illegal spirits during the last
12 months, the corresponding figures after 1 year were 42 and 14%. Significant
associations between being exposed to the campaign and reduced use and buying of
illegal spirits were found. Further, use and buying of illegal spirits at
baseline, and stopping to use and buy illegal spirits from baseline to follow-up
were analyzed in bivariate and multivariate logistic regression analyses. In the
multivariate prediction of stopping to use illegal spirits, only behavioral norms
and significant others' opinions (both measured at baseline) obtained
significance.
PMID- 10181026
TI - Assessing the reliability of a stage of change scale.
AB - The purpose of this study was to assess the test-retest reliability of a scale
measuring Prochaska's stages of change. Although structured questionnaire items
are being increasingly used to segment target audiences according to Prochaska
and DiClemente's stages of change, we could find only one report in the
literature assessing the reliability of such scales. The unreliability of single
item or algorithm questionnaire scales might be why a number of studies show only
minimal differences on some variables between individuals in different stages of
change. A survey of the Perth metropolitan general population aged 16-69 years (N
= 2629) was completed in August-September 1992 as part of a 3 year evaluation of
the Western Australian Health Promotion Foundation. The consistency of
respondents' responses was assessed across two questions measuring stages of
change for the behaviours quitting smoking (n = 404), reducing alcohol
consumption (n = 57) and doing more exercise (n = 704). Given the immediacy of
the test-retest situation, the reliability results are moderately encouraging:
kappa = 0.72, 0.73 and 0.52 for quitting smoking, reducing alcohol and doing more
exercise, respectively. Health researchers should be aware of the probable
moderate level of reliability if using the type of scale assessed in this study,
when interpreting differences between individuals in different stages. In
practice, several questionnaire items for classification purposes should be used
so that internal reliability measures can be calculated. It is recommended that
research be undertaken to devise more reliable scales for stages of change for
the various health behaviours. It is noted that the attitude literature with
respect to context and time specific intentions could be helpful in devising such
scales.
PMID- 10181027
TI - Health education for a breast and cervical cancer screening program: using the
ecological model to assess local initiatives.
AB - This study investigates the development and implementation of health education
strategies at the local level for a statewide breast and cervical cancer control
program. Baseline data on these initiatives were collected from 88 local
screening programs in North Carolina. Using the ecological model as a framework,
health education initiatives were assessed and analyzed to determine the level of
activity occurring at the local level and the comprehensiveness of programs.
Types and levels of interventions used are described and initial analysis is
provided of the impact these strategies are having on recruiting women from
target populations into these screening programs. Specific examples illustrating
the variety of interventions used at the individual, network, organizational and
community levels, and the impact of certain variables, such as the use of local
health education staff, on the comprehensiveness of interventions utilized, are
provided. The importance to practitioners of establishing process indicators in
assessing local initiatives and challenges to conducting evaluations of these
strategies are also discussed.
PMID- 10181028
TI - Accuracy of self-reported body weight: Stepped Approach Model component
assessment.
AB - This study was conducted to investigate innovative solutions to a measurement
problem pertaining to self-reported body weight data as a key component of the
Stepped Approach Model (SAM) of service delivery. Subjects (n = 223) were
randomly assigned to one of two conditions: Informed Group (of self-report and
weight measurement) + six body weighing habit items (IG, n = 113) and Uninformed
Group (of self-report and weight measurement) + one body weight item (UG, n =
110). A t-test indicated that IG subjects reported significantly more accurately,
t(194) = 2.99, P = 0.002, and with significantly less variability than UG
subjects, F(109,112) = 1.95, P < 0.0005. A multiple regression of absolute
difference weight (observed--self-reported weight) on observed weight revealed
consistent accuracy across the weight range for IG subjects, whereas UG subjects'
accuracy decreased as body weight increased. The slope of the IG did not
significantly differ from 0, t(218) = 1.44, P = 0.150, but did significantly
differ from the slope of the UG, t(218) = 2.78, P = 0.006. The following
conclusions are noted when IG conditions are used: (1) a three-component strategy
designed for maximum effect size results in accurate reporting across the entire
weight range, (2) self-reported body weights under prescribed conditions can be
used as valid 'proxies' for observed measurements, and (3) SAM proponents can
rely on the validity of self-report body weight as a credible basis for decisions
about changing intervention steps and evaluating intervention efficacy.
PMID- 10181031
TI - School-based health clinics and the role of mental health services: a review of
the literature.
AB - A review of school-based health clinics is provided with special attention to the
role of mental health services. An historical account of the development of
school-based health clinics is delineated as well as a description of school
based health clinics' purpose and unique role in providing health care for
children and adolescents. Critical policy issues are reviewed, such as managed
care's role in the school-based health clinics, research issues, and funding
concerns.
PMID- 10181032
TI - Childhood problems of alcoholic women.
AB - A sample of three hundred and nine alcoholic and non-alcoholic women in South
Carolina were asked three family of origin questions that were thought to relate
to the development of alcoholism. Specifically the women were asked: "While you
were growing up did anyone in your family (1) drink a lot, (2) use drugs, and (3)
serve a jail sentence." Results of multivariate odds ratio analyses indicate that
alcoholic women were 7.31 times more likely to report a family member who drank a
lot, 3.57 times more likely to report a family member who used drugs, and 5.6
times more likely to report a family member who served a jail sentence in their
families of origin. The prediction of alcoholism by any of these family of origin
variables did not differ as a function of age or race.
PMID- 10181033
TI - HIV risk among the homeless.
PMID- 10181034
TI - Paradigm change and uncertainty about funding of public health research: social
and scientific implications.
AB - Since the 1970s two fundamental shifts have occurred in health research funding:
a reduction in the buying power of research dollars, and an increase in the
competition for resources. Most fields have also seen a decrease in the dollars
available for research. Pressures for justifying the relevance of research
activities have become increasingly pragmatic. The thesis of this paper is that
scientific creativity and innovation are compromised by the highly uncertain and
competitive funding environment of contemporary health research. This is largely
because criteria of scientific excellence predicated on an investigation's
presumed future impact support the status quo of methods and subject matter in
funded research. Extraordinary rationality among scientists seeking and
allocating resources promotes the survival of the existing system over time, yet
inhibits progressive development through the transformation of conceptual models.
Therefore, despite a growing unrest about the way research on population health
is conducted, new conceptions of the relationship between theory and methods have
been slow to emerge. Amelioration of a disjunction between the institutionalized
rules governing science and the culturally sanctioned goals of science requires
commitment to a dialectic between orthodoxy and dissent.
PMID- 10181035
TI - The impact of lack of health insurance on children.
AB - This paper examines the impact that the lack of health insurance has on children
and their families. A random sample of families of children who were newly
enrolled in a children's health insurance program were interviewed by telephone
and asked about the children's health status, the amount of unmet need and
delayed care for a number of services, consequences of unmet need and delayed
care, usual activities, and the effect on the lack of health insurance. Data were
analyzed by using both quantitative and qualitative methods. We found that
uninsured children had experienced considerable unmet need and delayed care that
increased as the time without insurance increased. The parents reported some
adverse consequences. The children were also found to be limited in the extent to
which they could participate in various activities specifically because they
lacked health insurance. Finally, the parents reported considerable stress and
worry associated with their children's lack of coverage. We conclude that being
without health insurance has broad consequences for America's children.
PMID- 10181036
TI - Focus groups, program evaluation and the mentally ill: a case study.
AB - This article uses a case example to describe how focus group interviews were
utilized in evaluating mental health services for individuals with a serious and
persistent mental illness. The method, questions, and recruitment process are
summarized along with a description of the focus group interaction. Modifications
of logistic procedures and moderator skills are also presented along with the
limitations and benefits of using this method for the purpose of evaluation.
PMID- 10181037
TI - First AIDS vaccine: better than nothing.
PMID- 10181038
TI - Caught in the act. A striking 3-D snapshot of the AIDS virus reveals weak spots
in its armor.
PMID- 10181039
TI - Health reform is back in town.
PMID- 10181040
TI - Bringing the doctor to the (company) door.
PMID- 10181041
TI - When your health plan's stock plummets.
PMID- 10181042
TI - Not just another dinosaur.
PMID- 10181043
TI - What to look for in a PPO.
PMID- 10181044
TI - Sounding out hearing coverage.
PMID- 10181045
TI - Data watch. A downshift in benefit spending.
PMID- 10181046
TI - Data watch. Unscheduled absences hit a low.
PMID- 10181047
TI - In sugar we trust.
PMID- 10181048
TI - The epidemics of injecting drug use and blood-borne disease: a public health
perspective.
PMID- 10181049
TI - Controlling the global spread of infectious diseases: toward a reinforced role
for the international health regulations.
PMID- 10181050
TI - Medical devices; retention of three preamendment class III devices in class III-
FDA. Final rule.
AB - The Food and Drug Administration (FDA) is retaining the following three
preamendments class III devices in class III: Lung water monitor, powered vaginal
muscle stimulator for therapeutic use, and stair-climbing wheelchair. The agency
is taking this action because insufficient information exists to determine that
special controls would provide reasonable assurance of their safety and
effectiveness, and/or these devices present a potential unreasonable risk of
illness or injury.
PMID- 10181051
TI - Organ Procurement and Transplantation Network; final rule revision of comment
period and effective dates--HRSA. Extension of comment period and delay of
effective date for the Organ Procurement and Transplantation Network.
AB - This document sets forth the revisions required by the Fiscal Year 1998
Supplemental Appropriations Act, Public Law 105-174, signed into law by the
President on May 1, 1998. Section 4002 of that Act states that public comments on
the Organ Procurement and Transplantation Network (OPTN) Final Rule are permitted
until August 31, 1998, and that the OPTN rule will not become effective before
October 1, 1998. This document is provided to notify the public about these
provisions and to make corresponding changes to the regulation.
PMID- 10181052
TI - Statement of Organization, Functions and Delegations of Authority--HRSA.
PMID- 10181053
TI - Medicare program; establishment of the Medicare+Choice program--HCFA. Correction.
PMID- 10181054
TI - Civilian Health and Medical Program of the Uniformed Services (CHAMPUS); TRICARE
prime enrollment procedures--DOD. Proposed rule.
AB - This proposed rule modifies the TRICARE Prime enrollment for active duty families
by specifying that the enrollment period is continuous rather than a 12 month
enrollment period and it allows monthly installment payments of enrollment fees
for those beneficiaries required to pay an annual fee in order to enroll in
TRICARE Prime. These modifications are being made because TRICARE will soon be
available wordwide for active duty family members.
PMID- 10181055
TI - Agency for Health Care Policy and Research. General reorganization; statement of
organization, functions, and delegations of authority.
PMID- 10181056
TI - Memorandum of understanding between the Food and Drug Administration and the
Defense Alliance for Advanced Medical Terminology--FDA. Notice.
AB - The Food and Drug Administration (FDA) is providing notice of a memorandum of
understanding (MOU) between FDA and the Defense Alliance for Advanced Medical
Terminology (DAAMT). The purpose of the MOU is to enable government agencies to
exchange information and jointly pursue research endeavors related to medical
device safety and effectiveness.
PMID- 10181057
TI - Enrollment--provision of hospital and outpatient care to veterans--VA. Proposed
rule.
AB - This document proposes to amend VA's medical regulations. The Veterans' Health
Care Eligibility Reform Act of 1996 mandates that VA implement a national
enrollment system to manage the delivery of healthcare services. Accordingly, the
medical regulations are proposed to be amended to establish provisions consistent
with this mandate. Starting October 1, 1998, most veterans must be enrolled in
the VA healthcare system as a condition of receiving VA hospital and outpatient
care. Veterans would be allowed to apply to be enrolled at any time. They would
be eligible to be enrolled based on funding availability and their priority
status. In accordance with statutory provisions, the proposed rule also states
that some categories of veterans would be eligible for VA hospital and outpatient
care even if not enrolled. This document further proposes to establish a "medical
benefits package" setting forth, with certain exceptions, the hospital and
outpatient care that would be provided to enrolled veterans and certain other
veterans.
PMID- 10181058
TI - The big glitch.
PMID- 10181059
TI - Medicare's blues.
PMID- 10181060
TI - Get ready for JCAHO: know the latest hot topics.
PMID- 10181061
TI - Boston ED links patients with substance abuse treatment.
PMID- 10181062
TI - HCFA agrees to rework E/M guidelines.
PMID- 10181063
TI - Industry-sponsored case-mix study moving ahead slowly, report expected in
September.
PMID- 10181064
TI - OIG says SNF agreement to waive copayments for health plan members may violate
anti-kickback law.
PMID- 10181065
TI - Major changes made to CARF's accreditation standards for subacute programs.
PMID- 10181066
TI - "Carving out" conditions from global capitation rates: protecting high-cost
patients, physicians, and health plans in a managed care environment.
AB - The purposes of this study were (1) to develop a method for identifying
individuals with high-cost medical conditions, (2) to determine the percentage of
healthcare spending they represent, and (3) to explore policy implications of
"carving out" their care from managed care capitation. Annual payments over a 2
year period to enrollees of three health plans--a traditional managed care
organization, and a state Medicaid program--were determined by using a cross
sectional analysis of insurance claims data. The main outcome measures were the
number of enrollees with total annual payments in excess of $25,000 and the
contribution of these high-cost enrollees to each health plan's total costs.
Forty-one groups of diagnosis and procedure codes representing a combination of
acute and chronic conditions were included on the list of carve-out conditions.
Pulmonary insufficiency and respiratory failure together accounted for the
largest number of high-cost individuals in each health plan. Solid organ and bone
marrow transplants, AIDS, and most malignancies that required high-dose
chemotherapy were also important. The carve-out list identified more than one
third of high-cost individuals enrolled in the Medicaid program, approximately
20% of high-cost managed care enrollees, and 10% of high-cost fee-for-service
enrollees. These data confirm that it is possible to identify high-cost
individuals in health plans by using a carve-out list. Carving out high-cost
patients from capitation risk arrangements may protect patients, physicians, and
managed care organizations.
PMID- 10181067
TI - Delivery of preventive healthcare to older African-American patients: a
performance comparison from two practice models.
AB - While there is an increasing recognition by primary care providers of the
importance of preventive health services (PHS), the delivery of such services has
in general been substandard in many ambulatory care settings. Patient
sociodemographic status and the structural and operational procedures of
different clinic models are all believed to affect delivery of PHS. We conducted
a 2-year, retrospective, sequentially randomized chart analysis of African
American patients above age 50, comparing primary, secondary, and tertiary PHS
performance rates in two practice models: a medicine resident/faculty physician
clinic (MR) and a nurse practitioner/faculty physician clinic (NP).
Sociodemographics, disease profile, and PHS completion rates from 132 NP and 111
MR patient charts were abstracted. Apart from age, sociodemographic features were
similar in both patient groups. While there were differences between clinics with
regards to disease profiles (P < 0.05), and the higher number of diseases per
patient (P < 0.0001) in the MR population, the NP collaborative practice had
significantly better PHS performance. Rates of immunization
(influenza/pneumococcal), pelvic/pap and prostate examinations, stool-guaiac
testing, mammography, and functional assessment (activities of daily living,
instrumental activities of daily living, and mental status testing) were > 90% in
the NP and < 60% in MR patients. Although lower completion rates were found for
dietary counseling (60%), auditory screening (36%), dental examination (41%), and
obtaining advanced directives (24%) in the NP clinic, the rates were higher than
those for the MR clinic. In this NP collaborative model, a high level of
preventive health services was delivered while providing primary care to an
older, inner city, African-American population of low socioeconomic means.
PMID- 10181068
TI - Insurance type and the transportation to emergency departments of patients with
acute cardiac ischemia: the ACI-TIPI Trial Insurance Study.
AB - The relationship of insurance type to treatment-seeking behavior (ie, the
transportation to emergency departments of patients with symptoms suggestive of
acute cardiac ischemia) was evaluated. The focus was on comparing patients
belonging to a health maintenance organization (HMO) with patients who had
indemnity insurance. Data were collected prospectively on 10,783 patients
presenting to emergency departments of 10 adult care hospitals in the Eastern and
Midwestern United States between April and December 1993 as part of a clinical
trial. A total of 6,604 patients presented within 24 hours of symptom onset.
Although these patients as a group had a wide range of demographic and clinical
characteristics, persons belonging to an HMO and those with indemnity insurance
were very similar. The main outcome measures were whether the patient was
transported by ambulance and the duration of time from symptom onset to emergency
department arrival. A hospital-matched sample of HMO-insured and indemnity
insured patients allowed multivariable regression: HMO membership was not
associated with a different rate of ambulance use (odds ratio = 1.0; 95%
confidence interval = 0.73, 1.35) or duration of time from symptom onset to
emergency department presentation (6 minutes less, P = 0.8). HMO participation
was not related to treatment-seeking behavior, as reflected by ambulance use and
duration of time from symptom onset to emergency department arrival. However,
studies of more constrained managed care organizations and of broader ranges of
patients are needed.
PMID- 10181069
TI - Does competition by health maintenance organizations affect the adoption of cost
containment measures by fee-for-service plans?
AB - How groups insured by fee-for-service health plans react to increased competition
from health maintenance organizations (HMOs) is an unresolved question. We
investigated whether groups insured by indemnity plans respond to HMO market
competition by changing selected health insurance features, such as deductible
amounts, stop loss levels, and coinsurance rates, or by adopting utilization
management or preferred provider organization (PPO) benefit options. We collected
benefit design data for the years 1985 through 1992 from 95 insured groups in 62
US metropolitan statistical areas. Multivariate hazard analysis showed that
groups located in markets with higher rates of change in HMO enrollment were less
likely to increase deductibles or stop loss levels. Groups located in markets
with higher HMO enrollment were more likely to adopt utilization management or
PPO benefit options. A group located in a market with an HMO penetration rate of
20% was 65% more likely to have included a PPO option as part of its insurance
benefit plan than a group located in a market with an HMO penetration rate of 15%
(p < 0.05). Concern about possible adverse selection effects may deter some fee
for-service groups from changing their health insurance coverage. Under some
conditions, however, groups insured under fee-for-service plans do respond to
managed care competition by changing their insurance benefits to achieve greater
cost containment.
PMID- 10181070
TI - Safety and clinical efficacy of zileuton in patients with chronic asthma.
AB - Zileuton, a leukotriene pathway inhibitor used to treat asthma, improves lung
function, relieves symptoms, and is well tolerated. The purpose of this 12-month,
parallel-group, open-label study was to assess the efficacy of zileuton and
evaluate liver function in patients treated with this drug (approximately 2% of
patients treated with zileuton in controlled trials had reversible liver enzyme
elevations). A total of 2,947 patients at 233 centers in the United States were
randomly assigned in a 5:1 ratio to treatment with zileuton plus usual asthma
care or usual asthma care alone. Efficacy variables included asthma
exacerbations; need for alternative treatment, steroid rescue, emergency care,
and hospitalizations; forced expiratory volume in 1 second (FEV1); and asthma
symptom scores. The safety evaluation included measurement of alanine
aminotransferase levels. Patients treated with zileuton had significantly fewer
corticosteroid rescues (P < 0.001), required less emergency care (P < 0.05), had
fewer hospitalizations, and had greater increases in FEV1 (P = 0.048). They also
had significantly greater improvements in asthma symptoms. Increases in alanine
aminotransferase levels to three times or more the upper limit of normal occurred
in 4.6% of patients treated with zileuton and 1.1% of those receiving usual care
(P < 0.001); most increases occurred during the first 2 to 3 months. Alanine
aminotransferase levels decreased to less than two times the upper limit of
normal or to baseline levels during zileuton treatment or after drug cessation.
Jaundice or chronic liver disease did not develop in any patient. Adding zileuton
to the therapeutic regimens of patients with asthma is likely to improve asthma
control and lower utilization of healthcare resources.
PMID- 10181071
TI - A pharmacoeconomic analysis of rimexolone for the treatment of ophthalmic
inflammatory conditions.
AB - Topical steroids are the standard first-line therapy for treating ophthalmic
inflammatory conditions. However, potent ophthalmic steroids can lead to an
elevation of intraocular pressure (IOP), which can result in greater medical
resource utilization and increased costs. We have developed a decision analysis
model from a societal perspective to evaluate the costs and consequences of the
treatment of ophthalmic inflammatory conditions with two potent topical steroids:
prednisolone and rimexolone. Data for the model are based on information from
clinical trials, national data-bases, published literature, and responses by
ophthalmologists to a questionnaire on treatment patterns for elevated IOP. Three
steroid-responsive conditions are examined separately with the model: uveitis;
postoperative inflammation following cataract surgery; and other ophthalmic
inflammatory conditions (blepharitis, episcleritis, postoperative refractive
surgery, and corneal transplant). The model evaluates patients with acute
conditions versus those with chronic conditions and those with mild to moderate
elevation of IOP versus those with severe elevation of IOP. Although the unit
cost of rimexolone is higher than that of prednisolone, use of rimexolone leads
to cost savings because the incidence of elevated IOP is decreased. If rimexolone
is used instead of prednisolone for the treatment of ophthalmic inflammatory
conditions, the estimated cost saved (at 1995 AWP prices) is approximately $10
million across the entire US population. The savings across the health
maintenance organization population on an annualized basis is approximately $3.9
million. Even if rimexolone were priced higher than current market charges (at
130% to 150% of the AWP of prednisolone), cost savings ranging from the $2.9
million to $720,000 would accrue with use of rimexolone compared with
prednisolone. However if, rimexolone were priced at 160% of the AWP of
prednisolone, its use would incur an additional cost of $300,000. The primary
medical resource utilized in treating elevated IOP in ophthalmic inflammatory
conditions is physician visits. Medications are responsible for only one-fifth to
one-third of the total cost of treating elevated IOP. This analysis indicates
that rimexolone is associated with decreased medical resource utilization and
cost savings to the entire healthcare system.
PMID- 10181072
TI - Identification and case management in an HMO of patients at risk of preterm
labor.
AB - We carried out a study of pregnant patients in a health maintenance organization
to identify and provide case management of women at risk of preterm labor and to
determine important risk factors for preterm labor in a managed care population.
Data were collected on 794 women who completed an initial prenatal care visit at
HealthAmerica of Pittsburgh between July 15, 1994, and March 31, 1995, and
delivered at a local Pittsburgh hospital. The patients were assessed during an
initial call to schedule their first prenatal visit and also at the 8- to 15-week
and 24- to 28-week prenatal visits. Patients scoring 10 or higher on the risk
assessment form were referred to a nurse case manager who provided education and
support. Results of a logistic regression analysis suggest that the risk
assessment tool was effective in identifying women at risk for preterm labor.
"Physical/stressful work", as assessed by the patient, history of a prior preterm
birth, and multiple gestation were all statistically significant predictors of
preterm birth. Further research is needed to confirm the finding that physical or
stressful work is a significant predictor of preterm births and to determine
which aspects of the work may increase the patient's risk. This study was based
on 8 months of data; however, additional program implementation is needed to
evaluate fully the potential long-term benefits of the program.
PMID- 10181073
TI - Chronic ambulatory outpatients and four-vector management.
AB - Many psychiatrist and other mental healthcare professionals consider the
availability of atypical antipsychotic drugs a welcome advance in the treatment
of schizophrenia. Atypical agents have show to be effective against both positive
and negative symptoms of schizophrenia, and in general, their efficacy makes
patients more responsive to rehabilitation efforts. Although drugs are a
cornerstone of treatment, optimal management of chronic ambulatory outpatients
with schizophrenia also depends of psychosocial and other approaches. Still,
noncompliance needs to be addressed as schizophrenia patients often fail to take
their medications for a variety of reasons, including undesirable side effects
and lack of insight or denial of having a mental disorder. A four-vector model
for optimal management of chronic ambulatory outpatients includes the biological,
psychological, social, and spiritual domains. Although the resources for
providing comprehensive, forward-looking management are not universally available
in many areas of the United States, clinicians should always strive for the
ideal.
PMID- 10181074
TI - Atypical antipsychotics in the managed care era.
AB - Over the past decade, a new class of atypical antipsychotic drugs has been
developed for the treatment of schizophrenia and related conditions. This new
generation of antipsychotic agents represents the first significant breakthrough
in the treatment of schizophrenia since the advent of chlorpromazine in the early
1950s. Although the designation "atypical" is currently the most widely used term
for referring to these drugs, they are not likely to be viewed as atypical in the
future--given their rapidly increasing use as first-line agents. Increased
acceptance of these drugs early in the course of schizophrenia holds the promise
of real long-term benefits in outcome. Although the acquisition cost of these
drugs is significantly higher than that of older agents, pharmacoeconomic
analysis suggests the possibility of substantial reductions in the overall
financial burden posed by schizophrenic illness. This review summarizes the role
of atypical antipsychotics in the treatment of schizophrenia, their merits
compared to conventional medications, and their cost effectiveness.
PMID- 10181075
TI - Innovation is the hallmark of this pediatric asthma education program.
PMID- 10181076
TI - Comprehensive DM approach targets patients with multiple conditions.
AB - Disease management programs that address only a single disease are asking for
trouble, say some industry experts who favor a more comprehensive approach.
Trigon Blue Cross and Blue Shield's case management arm is taking heed, managing
patients--not diseases--using a sophisticated software system based on 'episode
treatment groups'.
PMID- 10181077
TI - Smoking cessation program focuses on pregnant women.
AB - Low-income pregnant women can and should quit smoking, and a simple program of
education mixed with support and follow-up has proven successful in a population
of public health patients. The women not only quit or reduced their smoking but
gave birth to babies that were heavier and healthier overall.
PMID- 10181078
TI - Flowcharts assist primary care MDs with diabetes diagnosis, treatment.
AB - A new federal report calls diabetes "an epidemic" but laments the fact that many
doctors fail to diagnose and manage the disease effectively. One physician says
this lack of attention to diabetes occurs because the majority of PCPs don't have
enough drug-specific know-how. You can use these two care flow sheets to help
both doctor and patient do a better job of managing the disease.
PMID- 10181079
TI - 'Clinical performance manager' integrates practice guidelines to enhance, monitor
DM efforts.
AB - A new software workstation that integrates widely accepted clinical practice
guidelines with patient demographic and provider information may be a godsend to
disease and demand management program planners looking to monitor, improve, and
document their results.
PMID- 10181080
TI - Early diagnosis of breast abnormalities. Florida Early Diagnosis Steering
Committee and Florida Academy of Family Physicians.
PMID- 10181081
TI - DM practice guidelines gathering a flood of advocates.
PMID- 10181082
TI - Complex chronic care patients managed using hospice model.
AB - Some patients just defy the traditional disease management model. Many are
elderly, have complex medical needs, and find comfort in their frequent visits to
the hospital emergency department. Find out how a pilot DM program is using
hospice and home health care providers as partners to help manage CHF and COPD
among the high-cost elderly, and how the DM approach maintains its effectiveness
even in the patients' final days.
PMID- 10181083
TI - DM programs getting off the ground at warp speed.
AB - You're under the gun to get multiple DM programs up and running in a very short
time frame--what do you do? This award-winning program hired full time DM
administrators, who rapidly created an array of initiatives using a team and a
guidelines-based approach.
PMID- 10181084
TI - Evidence continues to build: adjunctive behavioral therapy gives a boost to
outcomes.
AB - Mental health providers who just several years ago sought carve outs for their
services now say psychological issues are critical factors in the treatment of
diseases such as cancer and heart disease, and must be integrated with other
clinical services to achieve optimum outcomes and financial savings. Find out how
two ongoing DM efforts are integrating behavioral care, and why your organization
may want to follow suit.
PMID- 10181085
TI - Interactive video program cuts home care costs while slashing readmission rates.
AB - Get the details behind a sophisticated audio/video monitoring system that allows
chronically ill patients to get a medical check without ever leaving home. The
system is a potential godsend for rural providers, who can save loads of time and
travel dollars.
PMID- 10181086
TI - Marketplace. New U.S. appeals court ruling opens wide holes in ERISA preemption.
PMID- 10181088
TI - Abduction of newborn spurs press criticism of hospital security.
PMID- 10181089
TI - KY hospital avoids 'worst-case' scenarios during record March floods.
PMID- 10181087
TI - Perspectives. Viagra or bust: is pharmacy cost crisis unraveling HMO utilization
strategy?
PMID- 10181090
TI - Security concerns affect and are affected by NY Hospital's new building.
PMID- 10181091
TI - Tips for employees on how to avoid becoming a victim of crime at work.
PMID- 10181092
TI - An interview with: Elliot Boxerbaum on hospital mergers and their impact on
security.
PMID- 10181093
TI - How new or expanded hospitals can pose challenges to security, safety.
PMID- 10181094
TI - Securing busy hospital garages and lots in urban centers: how four hospitals and
a medical school are meeting today's and tomorrow's challenges.
AB - Parking lots and garages, besides being by definition targets for auto theft and
break-ins, like emergency rooms record a proportionately higher number of
incidents of a serious nature compared to other hospital areas. These include
burglaries, robberies, and assaults. Whether the parking facilities are located
in high-traffic urban centers or are providing services that attract victims of
serious crimes, the need to maintain and upgrade parking security is a high
priority for the hospital security executives interviewed for this report. Here,
they give details on the steps they are currently taking or plan to take to
provide round-the-clock protection for a wide range of parking patrons--patients
and visitors as well as doctors, nurses, other employees, and students.
PMID- 10181095
TI - Service reconfiguration: preparing for clinical integration.
PMID- 10181097
TI - Managing a group practice successfully.
PMID- 10181096
TI - The future of the gatekeeper. Some organizations are finding ways to modify the
"gatekeeper" role and meet the public's demand for increased access.
PMID- 10181098
TI - Trust and physician payment.
PMID- 10181099
TI - Rethinking customer service.
PMID- 10181100
TI - New rules coming soon. An expanded transfer definition and a new payment system
may have adverse implications.
PMID- 10181101
TI - Public policy statement. The healthcare executive's role in community health
improvement. November 1997. American College of Healthcare Executives.
PMID- 10181102
TI - Physicians and CQI. Clinical teams pave the way for quality improvement.
PMID- 10181103
TI - Cyberlaw and the workplace.
PMID- 10181104
TI - Of mutual interest. Aligning physicians' interests with those of your
organization.
PMID- 10181105
TI - A common sense review of personal protective equipment. Safety smarts.
AB - Approach the use and need for PPE with common sense, which too many people seem
to have set aside because of fear and emotion regarding occupational risk for
exposure. As providers, approach emotion with factual educational information
received in training programs that focus on medical facts--not fear. Fact: Yes,
we risk contracting a disease when we provide health care; however, data clearly
shows we run only a low risk. Fact: Because department budgets continue to
shrink, we need to purchase wisely. Fact: Sharps injuries represent 80 percent of
health care worker exposures. This is where the focus of our attention should be.
Fact: PPE use to block the mode of entry for blood/OPIM has been effective for
centuries and is scientifically sound. EMS, fire and rescue agencies should focus
on creating the proper perspective regarding the risk for disease transmission
and utilize a common-sense approach to the use of PPE.
PMID- 10181106
TI - 41 tips to avoid unnecessary exposures.
PMID- 10181107
TI - The Phoenix fanny pack. An infection protection accessory for all occasions.
AB - Arrangement of Fanny Pack Contents Back zippered compartment Sanitary wipes,
Paper sleeves, N-95 mask, Front zippered compartment: Plastic eyewear, Latex
gloves, Velcro flap compartment: Scissors, Penlight, glasses and tape. And
because providers must document everything, many also carry a pen, pencil and
notepad in the pack. The fanny pack for infectious control items has been a big
hit for the Phoenix Fire Department and many others throughout the country. The
pack removes several bulky items from medical boxes and vehicles, leaving them
less cluttered and better organized. The pack also helps departments avoid the
costly loss of staff hours due to illness. But most importantly, the packs put
essential protective items within quick and easy reach of responders, so they can
protect themselves and patients from unnecessary exposure to infectious diseases.
PMID- 10181108
TI - Good news for HMOs? They outperformed other plans, consumer survey says.
PMID- 10181109
TI - AHA revisits reform. Board may endorse plan to cover unemployed workers.
PMID- 10181110
TI - Ruling from on high. Supreme Court to hear 'dumping' case.
PMID- 10181111
TI - The best defense ... HHS, Justice use new guidelines to spike fraud bill.
PMID- 10181112
TI - AHA hires info technology guru.
PMID- 10181113
TI - Pulling up stakes. Anthem's Ohio exit may signal Medicare risk HMO trend.
PMID- 10181114
TI - Austerity plan. Total giving to hospitals drops to lowest level since '84.
PMID- 10181115
TI - Managed-care coalition splinters.
PMID- 10181116
TI - PHOs losing steam. Chandler PHO is second in Arizona to fold this year.
PMID- 10181117
TI - AHA, AAHSA to work together.
PMID- 10181118
TI - A competition problem. Effort to bid for Medicare rates has bogged down.
PMID- 10181119
TI - Managed-care comeback. System uses painful HMO experience to avoid problems with
its Medicare PSO.
PMID- 10181120
TI - Will PSOs be a disaster or a dream?
AB - The healthcare landscape is littered with failed attempts by hospitals and
physicians to manage insurance risk. This year's survey of managed-care plans
shows 12 of 30 provider-owned HMOs lost money in 1997. And Modern Healthcare's
news pages have chronicled recent losses at more than 20 provider-owned plans.
With provider-sponsored organizations in the pipeline, the question is: Will they
be a dream or are they a disaster in the making?
PMID- 10181121
TI - PSO lessons don't come easy or cheap.
PMID- 10181122
TI - Survey: providers exiting insurance.
PMID- 10181123
TI - Noting ER trends could help avert health disasters.
PMID- 10181124
TI - Hospitalists gain ground. The next issue is whether using them should be
mandated.
PMID- 10181125
TI - In the interest of patients. Added safeguards sought in healthcare bankruptcies.
PMID- 10181126
TI - HCFA expects PSO trickle, not flood.
PMID- 10181127
TI - HCFA's year-2000 fear grounds new projects.
PMID- 10181128
TI - Reinventing the COO. After being down and out, the position is back--but with
some changes.
AB - As hospitals have merged into systems and managed care has raised new cost
concerns, the traditional hospital chief operating officer has often been the odd
man out. But the position, which now carries various titles, is enjoying a
resurgence as integrated organizations see a need for one person to oversee all
activities. "You need a vision of where the organization is going and how to get
there," said Rhonda Anderson (left), executive vice president/COO at Hartford
(Conn.)Hospital.
PMID- 10181129
TI - The first gatekeeper. Healthcare ads target women as key decisionmakers.
PMID- 10181130
TI - On the same page. Clinicians, IS specialists agree on what clinical data
repositories should do.
PMID- 10181131
TI - Philanthropic confusion. Hospitals now pitch community need, not their own.
PMID- 10181132
TI - Why volunteers matter.
PMID- 10181133
TI - AHA centennial--the first 50 years.
PMID- 10181134
TI - Where the evolution began. Colonial doctor gave American hospitals a
revolutionary beginning.
PMID- 10181135
TI - The forgotten pandemic. The Spanish Flu of 1918 was gravest crisis American
hospitals had ever faced.
PMID- 10181136
TI - He had a big heart.
PMID- 10181137
TI - Americans with Disabilities Act: looking back and moving forward.
PMID- 10181138
TI - All approaches to preventing or reversing effects of stress are not the same.
PMID- 10181139
TI - The association between physical fitness and diagnosed chronic disease in health
maintenance organization members.
AB - PURPOSE: The purpose of this investigation was to determine the relationship
between predicted cardiorespiratory fitness (predicted VO2max) and diagnosed
chronic disease. DESIGN: A stratified random sample of individuals was surveyed.
SETTING: Large Health Maintenance Organization (HMO) in the upper Midwest.
SUBJECTS: HMO members (N = 8000), age 40 and over, with none, one, or two or more
of the following diagnosed chronic conditions: hypertension, diabetes,
dyslipidemia, and heart disease. MEASURES: Predicted VO2max was estimated for
those respondents who completed the survey providing all critical data elements
(n = 4121; representing 51.5% of total sample). Predicted VO2max was compared
across chronic conditions using analysis of variance. The proportion of subjects
across fitness quintiles by number of chronic conditions was tested using the chi
2 test. RESULTS: Subjects without chronic conditions showed higher predicted
VO2max values (29.8 +/- 7.7 ml/kg/min) than those with one (25.9 +/- 7.8
ml/kg/min) or two or more conditions (25.7 +/- 7.9 ml/kg/min) (p < .0001).
Subjects with diabetes, hypertension, and heart disease reported lower predicted
VO2max than their healthier counterparts (p < .0001), but this was not the case
for dyslipidemia subjects (27.6 +/- 7.6 vs. 27.4 +/- 8.2 ml/kg/min, respectively;
p > .58). A larger proportion of diseased subjects was in the lowest fitness
quintile for diabetes, hypertension, and heart disease, but not for dyslipidemia.
CONCLUSIONS: As a group, chronic disease patients appear to have lower levels of
physical fitness than subjects without chronic disease. Physical fitness
improvement in diseased populations should be supported in the clinical setting.
PMID- 10181140
TI - The use and impact of incentives in population-based smoking cessation programs:
a review.
AB - PURPOSE: This review discusses current published literature on population-based
smoking cessation interventions that involve incentives and examines whether such
interventions are effective in reducing the prevalence of smoking. SEARCH METHOD:
Studies published between 1975 and Spring 1997 were identified through a
computerized search of four electronic databases (MEDLINE, HEALTH, CINAHL, and
PSYCINFO) and reference lists of key articles using the following key words:
(smoking cessation OR quit smoking) AND (contest OR competition OR incentive OR
lottery OR quit and win). This search yielded 79 articles. To be included,
studies had to be published in English and had to have presented either quit
rates or participation rates for an incentive-based program that used population
based recruitment. Of the 79 articles, 17 met these criteria. FINDINGS:
Population-based interventions generally attract 1 to 2% of the target
population, but these participation rates can potentially be increased through
the use of innovative recruitment techniques. No specific type of recruitment
strategy was shown to be consistently more effective than others. There is no
evidence that particular types of incentives are able to influence participation
or quit rates, but the size of an incentive does appear to be important, with
larger incentives viewed as more effectively motivating smokers to quit and stay
smoke free than smaller ones. Estimates of the cost per quitter have ranged from
less than $20 to over $400. There are some indications that the costs of such
programs compare favorably with smoking cessation classes or clinic-based
approaches. CONCLUSION: Incentive-based smoking cessation programs that target an
entire community have the advantage of reaching a large and diverse group of
smokers. They may, however, attract only smokers who are already motivated to
quit. Realistically, incentive-based programs aimed at the general population can
expect 1% of all their smokers to quit smoking. Quit rates among participants may
initially be high (i.e., mean quit rate of 34% at 1-month follow-up) but decrease
over time (i.e., mean rate of 23% at 1 year). The results of this review suggest
a continued need to establish standard and valid criteria for the evaluation of
smoking cessation interventions. Methodological differences among existing
studies make them difficult to compare and interpret.
PMID- 10181141
TI - Use of self-help materials and smoking cessation among proactively recruited and
volunteer intervention participants.
PMID- 10181142
TI - Association of the health-promoting workplace with trade unionism and other
industrial factors.
AB - PURPOSE: The study examines associations of five healthy workplace attributes
with trade unionism and nine other industrial and sociodemographic factors. The
aims were to illustrate the measurement of workplace health promotion indicators
in Western Australia and to identify associations leading to a better
understanding of determinants of the healthy workplace. DESIGN: Personal and
telephone cross-sectional surveys were performed using population-based sampling
frames. The overall response rate was 72%. SETTING: Workplaces in Western
Australia. SUBJECTS: Random samples of household respondents aged 16 to 69 years
in 1992 (n = 1310) and 1994 (n = 1113). MEASURES: Measures of association between
healthy workplace attributes and trade unionism were adjusted for workplace
location, size, sector, and industrial classification. RESULTS: Trade unionism
was strongly associated with healthy catering practices (adjusted OR 2.05; 95% CI
1.30 to 3.23), sun protection practices (2.66; 1.69 to 4.17), disability access
(1.47; 1.10 to 1.95), and worksite health promotion programs (2.56; 2.07 to
3.17). A weak and nonsignificant association was observed with restrictive
smoking policies (1.21; .95 to 1.55). Generally, healthy workplace attributes
were reported less often by respondents working in rural locations, in the
private sector, and at small worksites. There was no consistent relationship with
sociodemographic factors, including an index of social disadvantage, but members
of blue-collar occupations experienced a low prevalence of restrictive smoking
policies. CONCLUSIONS: The study raises the hypothesis, but cannot confirm, that
trade unions could provide a means for employees to pursue the creation of a
health-promoting workplace. Small business represents an excellent target for
health promotion activities.
PMID- 10181144
TI - Are health risks related to medical care charges in the short-term? Challenging
traditional assumptions.
AB - PURPOSE: This study examines the association between self-reported health risks
and short-term use of medical resources. DESIGN: Cross-sectional study comparing
responses from a mailed survey with medical encounter and expenditure data.
Bivariate analyses and multivariate linear and logistic regressions controlling
for age, gender, and health status were conducted to illustrate the relationship
between selected risk factors and resource use. SETTING: A group network model
health maintenance organization (HMO) in Minneapolis, Minnesota. SUBJECTS: The
study population was comprised of a randomly selected sample of nonsenior adults
(18 to 64 years old, n = 3825) and seniors (65 years and older, n = 1955) who
were enrolled in an HMO. The response rate was 72%. MEASURES: Five independent
variables: smoking, alcohol use, obesity, lack of physical activity, and
unhappiness were derived from a questionnaire designed to assess health status
and health risks. Outcome measures were medical care charges and use of hospital
services. RESULTS: Obesity, physical inactivity, and unhappiness were related to
higher charges among seniors. These relationships dissipated to some degree after
controlling for age, gender, and health status. Unexpected differences were found
for alcohol use among both age groups, with those considered to be "not at risk"
accruing higher charges and demonstrating a higher likelihood of using inpatient
hospital services than those defined to be at risk. CONCLUSIONS: Bivariate and
multivariate regression results demonstrated that traditional risk factors are
weak and inconsistent predictors of short-term medical charges. Charging smokers
and other high risk individuals a higher annual insurance premium than is offered
for those at low risk raises questions about fairness when such risk factors are
not necessarily good predictors of short-term resource use. The rationale for
insurance cost-shifting should be supported with reliable data connecting risks
to charges.
PMID- 10181145
TI - User-centered design: principles to live by.
PMID- 10181143
TI - Recruiting African-American women to community-based health promotion research.
PMID- 10181147
TI - Universal design in housing.
AB - Universal design in housing is a growing and beneficial concept. It is subtle in
its differences from barrier-free, accessible, and industry standard housing.
Accessibility standards and codes have not mandated universal design and do not
apply to most housing. Universal design exceeds their minimum specifications for
accessible design and results in homes that are usable by and marketable to
almost everyone. Universal homes avoid use of special assistive technology
devices and, instead, incorporate consumer products and design features that are
easily usable and commonly available.
PMID- 10181146
TI - Public policy affecting universal design.
AB - The federal government has passed numerous laws that have focused on everything
from civil rights legislation to accessibility mandates. This paper looks at the
cumulative effects of federal legislation and nonlegislative activities on
breaking down the wall of inequality for persons with disabilities and promoting
the concept of universal design and universal access.
PMID- 10181148
TI - Universal design and assistive technology in communication and information
technologies: alternatives or complements?
AB - Universal design and assistive technology present advantages and disadvantages in
accommodating the needs of people with disabilities. The best solution may be a
combination of the two, using universal design wherever possible and commercially
practical and using assistive technologies wherever it is necessary or provides
sufficient additional advantage to the user. Three approaches are discussed for
the individual who is unable to interact with their world: change the individual,
provide them with tools they can use, or change the environment. Examples of each
are illustrated using personal workstations and shared, public, and encountered
systems. The final decision may rest on commercial practicality, and several new
technologies are explored. Ultimately, we need to continue to move forward both
on the universal design and the assistive technology fronts if we are to address
the needs of people with disabilities and those who are aging.
PMID- 10181149
TI - Assistive technology and universal design in the workplace.
AB - The terms assistive technology and universal design challenge designers,
engineers, and technologists to consider the broadest possible use for the things
they create, to make assistive technology as useful to nondisabled persons as to
those with disabilities, and to make the products and environments we design as
usable as possible for everyone, regardless of age or ability.
PMID- 10181150
TI - Maximizing usability: the principles of universal design.
AB - The Center for Universal Design at North Carolina State University has developed
a set of seven Principles of Universal Design that may be used to guide the
design process, to evaluate existing or new designs, and to teach students and
practitioners. This article presents preceding design guidelines and evaluation
criteria, describes the process of developing the Principles, lists The
Principles of Universal Design and provides examples of designs that satisfy
each, and suggests future developments that would facilitate applying the
Principles to assess the usability of all types of products and environments.
PMID- 10181151
TI - From barrier-free to universal design: an international perspective.
AB - What is universal design? And where lies the difference between barrier-free
design and universal design? One can answer this question from different
viewpoints. This paper attempts to answer the question from the Far East, where
the idea came later than in the United States or Europe.
PMID- 10181152
TI - The voice of the customer--Part 2: Benchmarking battery chargers against the
Consumer's Ideal Product.
AB - The Rehabilitation Engineering Research Center on Technology Evaluation and
Transfer is exploring how the end users of assistive technology devices define
the ideal device. This work is called the Consumer Ideal Product program. In this
work, end users identify and establish the importance of a broad range of product
design features, along with the related product support and service provided by
manufacturers and vendors. This paper describes a method for systematically
transforming end-user defined requirements into a form that is useful and
accessible to product designers, manufacturers, and vendors. In particular,
product requirements, importance weightings, and metrics are developed from the
Consumer Ideal Product battery charger outcomes. Six battery charges are
benchmarked against these product requirements using the metrics developed. The
results suggest improvements for each product's design, service, and support.
Overall, the six chargers meet roughly 45-75% of the ideal product's
requirements. Many of the suggested improvements are low-cost changes that, if
adopted, could provide companies a competitive advantage in the marketplace.
PMID- 10181153
TI - Will Congress respond to consumer health care concerns?
PMID- 10181154
TI - Vancomycin-resistant enterococci; the ultimate nosocomial pathogen?
PMID- 10181155
TI - Health care 2000: Part 3. Integration strategies.
PMID- 10181156
TI - Discrepancies in international normalized ratios (INR) in swine and humans.
PMID- 10181157
TI - Tracing our roots: the beginnings of a profession.
AB - OBJECTIVE: To examine the role of the American Society of Clinical Pathology and
the Board of Registry in shaping the field of clinical laboratory science during
its formative years. DESIGN: A survey of literature on the history of clinical
laboratory science was conducted. References consulted include various books and
professional journals. CONCLUSION: The Board of Registry played a significant
role in the early development of clinical laboratory science. The Board
established standards of competence for entry-level practitioners and a mechanism
for assessing competence and developed an accreditation process for educational
programs.
PMID- 10181158
TI - From student laboratory to clinical environment.
AB - OBJECTIVE: To describe a clinical laboratory practice simulation experience for
clinical laboratory science (CLS) students which was intended to improve the
transition from the student laboratory to the clinical environment. SETTING:
University of Kentucky Center for Rural Health, a rural health professions
education center for a state-assisted institution. PRACTICE DESCRIPTION:
Baccalaureate-level CLS program. PRACTICE INNOVATION: Clinical laboratory
practice simulation experience allows students to become familiar with the
clinical environment. It also allows faculty to assess student performance and to
provide students with feedback in a controlled setting. MAIN OUTCOME MEASUREMENT:
Perception of benefit from the simulation experience by CLS graduates. RESULTS:
CLS graduates report the simulation experience helped to prepare them for
practice in the clinical environment. CONCLUSION: Clinical laboratory simulation
can improve the transition to actual clinical laboratory practice and is a
valuable tool to evaluate pre-clinical deficiencies.
PMID- 10181159
TI - Laboratory cross training needs assessment.
AB - OBJECTIVE: To define the continuing education topics and methods in the area of
chemistry and hematology, that if developed, would best support the cross
training needs of hospital based laboratories in the State of Georgia. DESIGN: A
cross sectional study of hospital based laboratories in Georgia was completed
using surveys sent to 181 hospital laboratory managers and administrators.
Descriptive statistics were used to evaluate the survey results. SETTING:
Department of Medical Technology, Medical College of Georgia, Augusta GA.
PARTICIPANTS: Laboratory managers and administrators. INTERVENTION: Not
applicable. MAIN OUTCOME MEASUREMENTS: Four descriptive outcome measurements were
requested from each participant: 1) demographic questions, 2) cross-training
topics desired, 3) training material desired, and 4) computer literacy and
equipment assessment. RESULTS: Sixty-six surveys were completed and returned in a
usable form (36% return rate). Demographically, the respondent group is a
representative sample of hospital based laboratories in the State of Georgia with
46% of the respondents from facilities of 100 hospital beds or less. Respondents
desired that case study training topics be developed using paper and computer
assisted instruction mediums. Additionally, respondents desired that Professional
Acknowledgement for Continuing Education (P.A.C.E.) be associated with the
training material. They were willing to pay for this administrative service.
CONCLUSION: This cross sectional study assessed the cross-training needs of
hospital based laboratories in Georgia. Findings will allow educators to focus
and develop continuing education packages that best meet the needs of the
laboratorian workforce.
PMID- 10181160
TI - Tips for complying with JCAHO's most challenging laboratory standards.
AB - OBJECTIVE: Suggest how to comply with the JCAHO standards which have proven to be
most challenging in the survey process. DATA SOURCES: JCAHO Laboratory Survey
data. CONCLUSION: Previous prior planning is the key to meeting the standards set
forth by the JCAHO.
PMID- 10181161
TI - Quality and the attending physician statement.
PMID- 10181162
TI - Cystic fibrosis mortality: registry data of cystic fibrosis.
AB - BACKGROUND: The Cystic Fibrosis Foundation has been collecting mortality and
other data on cystic fibrosis patients from over 100 U.S. clinical centers since
1966, and publishes annual reports of the data. Cystic fibrosis is an important
autosomal recessive genetic disease, affecting multiple body systems, with
disability and early mortality as very common complications. RESULTS: Observed
data by age in the 1994 and 1995 REports are compared with the earliest Registry
experience. 1966-1972, after age-matching observed with expected mortality in the
U.S. population. Observed and expected results are given in four tables of
comparative mortality. CONCLUSION: Excess mortality as a rate difference has
shown a marked decrease during this time period, ranging from 96% at age 0-1 to
52% at ages 20-25 years. This can be attributed to improvements in medical
treatment.
PMID- 10181163
TI - Outcome of patients treated with a St. Jude prosthetic heart valve.
AB - BACKGROUND: Long-term outcome of patients treated with a St. Jude prosthetic
heart valve was reported by investigators in Lausanne, Switzerland. This article
quantifies the mortality and morbidity implications of single or multiple heart
valve replacement. RESULTS: After hospital discharge, mortality ratios were
highest for duration 5-10 years, roughly comparable in patients who received a
single valve, and generally higher in those who received both an aortic and a
mitral valve prosthesis. Outcome varied with preoperative myocardial function,
but there was no survival difference among subjects with a history of stenotic,
regurgitant, or mixed lesions. Postoperative complications included embolism,
anticoagulant-related hemorrhage, stroke, prosthesis thrombosis, endocarditis,
prosthesis dysfunction, hemolytic anemia, and reoperation. CONCLUSIONS: This
study indicated that overall mortality experience was fairly comparable in
patients who received a single St. Jude prosthetic heart valve and less favorable
in those who received multiple valves. Long-term morbidity rates following
insertion of a St. Jude prosthetic heart valve were high.
PMID- 10181164
TI - The relationship between length of vocational disability, psychiatric illness,
life stressors and sociodemographic variables.
AB - OBJECTIVE: The primary objective of this study was to examine the relationship
between vocational disability, psychiatric illness, life stressors and
sociodemographic factors. METHOD: Information on a variety of variables was
obtained from insurance files of 147 subjects who had submitted claims for
monetary compensation on grounds of psychiatric symptoms. RESULTS: The majority
of subjects received a diagnosis of mood disorder or anxiety disorder. Extended
vocational disability was associated with longer duration of psychiatric illness,
rating of poorer prognosis by the treating physician, and lower income and
occupational levels. Individuals with recent onset of disability reported more
stressors than those experiencing extended disability. CONCLUSION: Although
longer duration of psychiatric illness was associated with vocational disability,
other variables play an important role in accounting for extended vocational
disability.
PMID- 10181165
TI - AIDS analysis: experience from Savings Bank Life Insurance Company.
AB - BACKGROUND: In the period 1988 to the current, 44 AIDS claims were reviewed in
order to assess the policies regarding AIDS testing. RESULTS: The average age of
the applicant at time of issue was 30.5 years. 41 percent of the claims were for
less than $5000, but this represented less than 5% of the total claims losses.
CONCLUSION: As many as 34% of the applicants are likely to have anti-selected
based on policy duration and other factors.
PMID- 10181166
TI - Breast cancer: cured or not?
AB - Survival following treatment of breast cancer may be estimated through the
recognition of various prognostic factors. The Case Study presented here calls
attention to several of these factors. The reliability and relative value of
these prognosticators are discussed. Recommendations are offered for the
practical application of prognostic information in the determination of expected
mortality.
PMID- 10181167
TI - Questioning dogma in microbiology.
PMID- 10181168
TI - A consensus on Pap smear review.
PMID- 10181170
TI - Puzzling out a role for Alzheimer's tests.
PMID- 10181169
TI - Medicare regs and year 2000 challenge billing systems.
PMID- 10181171
TI - 'Jury is out' on value of combination GI test panel.
PMID- 10181172
TI - Privacy protection patchy for medical information.
PMID- 10181173
TI - Teledermatology survey 1998.
PMID- 10181174
TI - From early wireless to Everest.
AB - Medical information has been transmitted using wireless technologies for almost
80 years. A "wired wireless" electronic stethoscope was developed by the U.S.
Army Signal Corps in the early 1920's, for potential use in ship-to-shore
transmission of cardiac sounds. [Winters SR. Diagnosis by wireless. Scientific
American June 11, 1921, p. 465] Today, wireless is used in a wide range of
medical applications and at sites from transoceanic air flights to offshore oil
platforms to Mt. Everest. 'Wireless LANs' are often used in medical environments.
Typically, nurses and physicians in a hospital or clinic use hand-held "wireless
thin client" pen computers that exchange patient information and images with the
hospital server. Numerous companies, such as Fujitsu (article below) and Cruise
Technologies (www.cruisetech.com) manufacture handheld pen-entry computers. One
company, LXE, integrates radio-frequency (RF) enhanced hand-held computers
specifically designed for production use within a wireless LAN (www.lxe.com).
Other companies (Proxim, Symbol, and others) supply the wireless RF LAN
infrastructure for the enterprise. Unfortunately, there have been problems with
widespread deployment of wireless LANs. Perhaps the biggest impediment has been
the lack of standards. Although an international standard (IEEE 802.11) was
adopted in 1997, most wireless LAN products still are not compatible with the
equipment of competing companies. A problem with the current standard for LAN
adapters is that throughput is limited to 3 Mbps--compared to at least 10 Mbps,
and often 100 Mbps, in a hard-wired Ethernet LAN. An II Mbps standard is due out
in the next year or so, but it will be at least 2 years before standards
compliant products are available. This story profiles some of the ways that
wireless is being used to overcome gaps in terrestrial and within-enterprise
communication.
PMID- 10181175
TI - Tele-imaging enables hospital to extend its services world-wide.
PMID- 10181176
TI - 1999: the year of ADSL?
PMID- 10181177
TI - Digital subscriber lines--DSL in telemedicine.
PMID- 10181178
TI - Telepsychiatry background and activity survey. The development of telepsychiatry.
PMID- 10181179
TI - Thoughts from tele-mental health practitioners.
PMID- 10181180
TI - Urban kids receive telemedical care at school.
PMID- 10181181
TI - It's time to start practicing population-based health care.
PMID- 10181182
TI - Family physicians and nurse practitioners--a perfect team.
PMID- 10181183
TI - Web tools target patients.
PMID- 10181184
TI - Power shift. A new model for case management returns power to physicians--and
still promises to cut costs.
PMID- 10181185
TI - Finger pointing. Who's to blame for the lack of standards?
PMID- 10181186
TI - Starved for bandwidth. Beware: telemedicine and videoconferencing can strangle
your network.
PMID- 10181188
TI - Telehealth core to WHO's missions.
PMID- 10181187
TI - PharmAid.
PMID- 10181189
TI - U.K.'s NHS unveils IT strategy.
PMID- 10181190
TI - The snail trail. As integration dust settles, healthcare systems may inch closer
to enterprisewide answers.
PMID- 10181191
TI - The big picture. Is vision important? Only if you want to keep your job.
PMID- 10181192
TI - Process first, technology second. Improve efficiency and reduce costs through
efficient work processes.
PMID- 10181193
TI - Connectivity, content and competencies--the Internet Project in NHS East Anglia
and Oxford.
PMID- 10181194
TI - From A to Z: automated catalogue to Web OPAC and Z39.50.
PMID- 10181195
TI - More change ahead? You can depend on that! UK Health Service White Papers: new
opportunities for library and information services?
PMID- 10181196
TI - Intelligent purchasing in Trent: information for decision-making in the region's
health authorities.
AB - The realization of an evidence-based health service presents opportunities for
libraries to make a direct contribution to the decision-making process in the
delivery of health care. An example of such an opportunity is given through a
description of the Trent Working Group on Acute Purchasing, a network of health
authority purchasers that takes a research-based approach to making purchasing
decisions. The Working Group is supported by a multidisciplinary research team,
which includes an Information Officer. The role of the Information Officer in
supporting the process of the Working Group is described below; namely in the
setting of research priorities, in contributing to research projects and in
disseminating the outputs of the Working Group. The benefits of being involved in
such a project, both to the information service and to the Information Officer,
are summarized.
PMID- 10181197
TI - Attitudes to LIS education and academic-practitioner liaison: results of a survey
of members of the Library Association Health Libraries Group.
AB - A questionnaire survey was conducted by the Library Association Health Libraries
Group in October-December 1996. Information practitioners in the health care
sector were asked what they considered were the education and research needs of
the profession, their opinion of Library and Information Sciences education, and
their views on practitioner input to education and research. They were also asked
whether they would be prepared to give talks to students and to offer student
placements. The results show that there is still a considerable gulf between
academics and practitioners, and that although practitioners are enthusiastic
about getting more involved in liaison, they are constrained by lack of time and
resources. Practical solutions need to be found to encourage greater
understanding and closer working relationships, to achieve the benefits of
academic-practitioner liaison.
PMID- 10181198
TI - Heart-stopper in the cardiac unit.
PMID- 10181199
TI - For advice on teamwork and a long career, just ask Mr. C. Interview by Jaime
Shimkus.
PMID- 10181201
TI - So you want to be a consultant. Reality check: the good, the bad and the ugly.
PMID- 10181200
TI - Software shopping? Dump the old rules.
PMID- 10181202
TI - EtO Emergency. Think safety before a spill.
PMID- 10181203
TI - Get with the program. ORs still trail in supply automation.
PMID- 10181204
TI - Abuzz about fuzz.
PMID- 10181205
TI - Rx for survey jitters: do your homework.
PMID- 10181206
TI - Stats. IT managers still fighting for funds.
PMID- 10181207
TI - Managed care 1998. Playing the HMO game.
PMID- 10181208
TI - Let's play doctor.
PMID- 10181209
TI - Financial systems: the next generation.
AB - Changes in health care organizations and business styles are creating demand for
new financial applications that span enterprises, deliver managed care muscle to
providers, mesh with CPRs and solve Year 2000 concerns.
PMID- 10181210
TI - Managing diseases by managing IT.
PMID- 10181211
TI - Enterprise integration. Balancing people, places and times.
PMID- 10181212
TI - The CHIME/HMT CIO Roundtable: CIO skills.
PMID- 10181213
TI - Internet commerce and managed care.
PMID- 10181214
TI - What works. Small practice cuts claims processing from two months to two weeks,
saves $8,000 on ads.
PMID- 10181215
TI - What works. Web site unites multiple databases in one resource.
PMID- 10181216
TI - What works. Software enhances patient education for pediatrician.
PMID- 10181217
TI - HotList: practice management systems.
PMID- 10181218
TI - Managing patient care needs in the 21st century.
PMID- 10181219
TI - Data warehousing: not quite on target.
PMID- 10181220
TI - Portable productivity at the point of care.
AB - Managed care is motivating providers to explore ways to reduce costs by improving
performance at the point of care. One increasingly popular tool: portable and
wireless computers and software to help capture clinical data.
PMID- 10181221
TI - Paper cuts? HIPAA's (Health Insurance Portability and Accountability Act) new
rules.
AB - The effort to standardize electronic claims and other transactions continues to
move ahead as HIPAA rules near completion. The goal: a simpler, less paper
intensive system that saves money.
PMID- 10181222
TI - What works. Mainframe software links 3270 terminals to new lab system, avoids
$60,000+ investment in PCs.
PMID- 10181223
TI - What works. Claims system cuts state backlog, processing days.
PMID- 10181224
TI - What works. Laptop charting system helps home care agency increase visits per
day.
PMID- 10181225
TI - Deploying an HMO's data warehouse.
AB - Kaiser Permanente says it has saved millions of dollars and improved the quality
of care with information from its data warehouse. Here's how Kaiser implemented
the warehouse four years ago, and how it uses it today.
PMID- 10181226
TI - HotList: systems integration.
PMID- 10181227
TI - Building the framework for a computerized patient record.
PMID- 10181228
TI - Long Island hospital cooks up a successful fundraising recipe.
PMID- 10181229
TI - More choices, enhanced presentation and warmer ambiance characterize elderly care
foodservice.
PMID- 10181230
TI - Survey shows Americans may be drinking themselves to dehydration.
PMID- 10181231
TI - Foodservice information technology: getting better, quicker.
PMID- 10181232
TI - From curry to feta cheese, hospitals provide international flavor with more
ethnic offerings.
PMID- 10181233
TI - Hospitals are brewing success with specialty coffee sales.
PMID- 10181234
TI - The birth of the association.
PMID- 10181235
TI - Another 50th anniversary. World's first computer is coming back to life.
PMID- 10181236
TI - Making health records professional(s). A report by a joint project team involving
AMRO (now IHRIM).
PMID- 10181237
TI - Professionalism and qualifications.
PMID- 10181238
TI - Review of the educational achievements of the Institute.
PMID- 10181239
TI - What price progress?
PMID- 10181240
TI - A history of the NHS.
PMID- 10181241
TI - Key dates in the history of the NHS.
PMID- 10181242
TI - The history of AMRO.
PMID- 10181243
TI - Medicare program; prospective payment system and consolidated billing for skilled
nursing facilities; extension of comment period--HCFA. Notice of extension of
comment period for interim final rule.
AB - This document extends the comment period for an interim final rule with comment
period that was published in the Federal Register on May 12, 1998 (63 FR 26252).
That interim final rule implements provisions in section 4432 of the Balanced
Budget Act of 1997 related to Medicare payment for skilled nursing facility
services. Those include the implementation of a Medicare prospective payment
system for skilled nursing facilities, consolidated billing, and a number of
related changes. The comment period is extended for 60 days.
PMID- 10181244
TI - Schedule for rating disabilities: cold injuries--VA. Final rule.
AB - This document amends the Department of Veterans Affairs (VA) Schedule for Rating
Disabilities by revising the provisions governing evaluations for cold injury
residuals. The intended effect of this amendment is to provide evaluation
criteria based on current medical knowledge about the long-term effects of cold
injury that can be applied to any part of the body affect by cold injury.
PMID- 10181245
TI - Provision of drugs and medicines to certain veterans in state homes--VA. Interim
final rule with request for comments.
AB - This document amends the "Medical" regulations concerning the provision of drugs
and medicines prescribed by non-VA physicians for certain veterans who are
permanently housebound or in need of regular aid and attendance. The regulations
are amended to allow prescriptions to be filled by non-VA pharmacies in state
homes under contract with VA for filling prescriptions for patients in state
homes. This is consistent with VA's special relationship with state homes. It
will eliminate duplication of services and will help improve timeliness for
filling prescriptions in state homes.
PMID- 10181246
TI - Medical devices; investigational device exemptions--FDA. Proposed rule.
AB - The Food and Drug Administration (FDA) is proposing to amend the Investigational
Device Exemptions (IDE) regulation. The proposed regulatory changes are intended
to reflect amendments to the Federal Food, Drug, and Cosmetic Act (the act) by
the FDA Modernization Act of 1997 (FDAMA). These amendments provide that the
sponsor of an IDE may modify the device and/or clinical protocol, without
approval of a new application or supplemental application, if the modifications
meet certain criteria and if notice is provided to FDA within 5 days of making
the change. The proposed rule also defines the credible information to be used by
sponsors to determine if the criteria are met.
PMID- 10181247
TI - Memorandum of understanding between the Food and Drug Administration and the
Indian Health Service--FDA. Notice.
AB - The Food and Drug Administration (FDA) is providing notice of a memorandum of
understanding (MOU) between FDA and the Indian Health Service (IHS). The purpose
of the MOU is to develop a more cohesive relationship to mutually address
American Indian and Alaska Native issues within the context of each
organization's jurisdiction.
PMID- 10181248
TI - Statement of organization, functions and delegations of authority--HRSA. Office
for the Advancement of Telehealth (RAB).
PMID- 10181249
TI - Federal Employees Health Benefits Program improving carrier performance;
conforming changes--OPM. Proposed rulemaking.
AB - The Office of Personnel Management (OPM) is proposing to issue a regulation that
would amend the Federal Employees Health Benefits Acquisition Regulation (FEHBAR)
to underscore accountability for customer service and contractual compliance
among the Federal Employees Health Benefits (FEHB) Program community-rated
carriers. The regulation would enable OPM to better manage carriers' performance
over key contract areas, including customer service measures, information and
reporting requirements, and significant events that might affect service to
enrollees. Accurate and timely performance by carriers will facilitate the
Program meeting its customer service standards.
PMID- 10181250
TI - Privacy Act of 1974; report of altered systems--HCFA. Notice of the global
addition of three new routine uses to designated HCFA systems of records.
AB - HCFA is adding three additional routine uses to the Systems of Records specified
in Appendix A. These routine uses will permit HCFA to disclose individual
specific information for the purpose of combating fraud or abuse in the health
benefit programs administered by HCFA and for other compatible purposes. These
new routine uses will permit HCFA to make disclosures as follows: (1) To a HCFA
contractor, including but not necessarily limited to fiscal intermediaries and
carriers under title XVIII of the Social Security Act, to administer some aspect
of a HCFA-administered health benefits program, or to a grantee of a HCFA
administered grant program, which program is or could be affected by fraud or
abuse, for the purpose of preventing, deterring, discovering, detecting,
investigating, examining, prosecuting, suing with respect to, defending against,
correcting, remedying, or otherwise combating such fraud or abuse in such
program; (2) To another Federal agency or to an instrumentality of any
governmental jurisdiction within or under the control of the United States,
including any state or local government agency, for the purpose of preventing,
deterring, discovering, detecting, investigating, examining, prosecuting, suing
with respect to, defending against, correcting, remedying, or otherwise combating
fraud or abuse in a health benefits program funded in whole or in part by Federal
funds; and, (3) To any entity that makes payment for or oversees the
administration of health care services, for the purpose of preventing, deterring,
discovering, detecting, investigating, examining, prosecuting, suing with respect
to, defending against, correcting, remedying, or otherwise combating fraud or
abuse against such entity or the program or services administered by such entity,
subject to certain conditions.
PMID- 10181251
TI - TRICARE senior demonstration of military managed care--DOD. Notice of
demonstration project.
AB - This notice is to advise interested parties of a demonstration project in which
the Department of Defense (DoD) will provide health care services to Medicare
eligible military retirees in a managed care program, called TRICARE Senior, and
receive reimbursement for such care from the Medicare Trust Fund. The program is
authorized by section 1896 of the Social Security Act, amended by section 4015 of
the Balanced Budget Act of 1997 (P.L. 105-33). The statue authorizes DoD and the
Department of Health and Human Services (HHS) to conduct at six sites during
January 1998 through December 2000, a three-year demonstration under which dual
eligible beneficiaries will be offered enrollment in a DoD-operated managed care
plan, called TRICARE Senior Prime. The legislation also authorizes Medicare HMOs
to make payments to DoD for care provided to HMO enrollees by military treatment
facilities (MTFs) participating in the demonstration. This part of the
demonstration, to be called Medicare Partners, will allow DoD to enter into
contracts with Medicare HMOs to provide specialty and impatient care to dual
eligible beneficiaries currently provided on a space-available basis. Additional
legal authority pertinent to this demonstration project is 10 U.S.C. section
1092. Under TRICARE Senior Prime, Medicare-eligible military retirees who enroll
in the program will be assigned primary care manager (PCMs) at the MTF. Enrollees
will be referred to specialty care providers at the MTF and to participating
members of the existing TRICARE Prime network. TRICARE Senior Prime enrollees
will be afforded the same priority access to MTF care as military retiree and
retiree family member enrollees in TRICARE Prime. DoD will receive reimbursement
from HCFA on a capitated basis at a rate which is 95 percent of the rate HCFA
currently pays to Medicare-risk HMOs, less costs such as capital and graduate
medical education, disproportionate share hospital payments, and some capital
costs, which are already covered by DoD's annual appropriation. However, under
the authorizing statute, DoD must meet its current level of effort for its
Medicare-eligible beneficiaries before receiving payments from the Medicare Trust
Fund. That is, DoD must continue to fund health care at a certain expenditure
level for its Medicare-eligible population before it may be reimbursed by HCFA
for care provided to TRICARE Senior Prime enrollees. The Balanced Budget Act of
1997 required DoD and HHS to complete a memorandum of agreement (MOA) specifying
the operational requirements of the demonstration project. That MOA was completed
on February 13, 1998, and is published below. Except as provided in the MOA,
TRICARE Senior Prime will be implemented consistent with applicable provisions of
the CHAMPUS/TRICARE regulation, particularly 32 CFR sections 199.17 and 199.18.
PMID- 10181252
TI - Children with serious emotional disturbance; estimation methodology--SAMHSA.
Final notice.
AB - This notice describes the final methodology to identify and estimate the number
of children with a serious emotional disturbance (SED) within each State. This
notice is being published as part of the requirements of Public Law 102-321, the
ADAMHA Reorganization Act of 1992.
PMID- 10181253
TI - Playing footsie with health care.
PMID- 10181254
TI - Bitter medicine.
AB - More than any other Republican on Capitol Hill, Rep. Charlie Norwood has forced
his party's leaders to confront an issue that they had wished would simply go
away: American's dissatisfaction with their health insurance plans.
PMID- 10181255
TI - Teens and sex.
AB - The rate of births to teenagers is down, but who gets the credit? While policy
initiatives have been deemed largely ineffective, efforts to shape popular
culture through the media are faring better.
PMID- 10181256
TI - Shifting roles. Health care organizations are redefining the duties of Webmasters
as the use of Internet technologies grows in importance.
PMID- 10181257
TI - 'Dr. Bill' wears many hats. Interview by Dan Balaban.
PMID- 10181258
TI - HMOs slow to embrace client/server systems.
PMID- 10181259
TI - Innovators 1998. Making eye care more accessible.
AB - Two pioneering physicians establish a teleophthalmology clinic in a Los Angeles
public housing development.
PMID- 10181260
TI - Innovators 1998. Tufts puts its data to good use.
AB - The managed care company uses a data warehouse to identify candidates for
preventive programs and generate custom reports for its customers.
PMID- 10181261
TI - Innovators 1998. Going with what works.
AB - At Scott & White Hospital and Clinic, physicians still dictate their clinical
information for transcription. But Internet technologies enable easy access to
electronic records.
PMID- 10181262
TI - Innovators 1998. Corralling all clinical information.
AB - BJC Health System has created an intranet to give clinicians at multiple sites
easier access to data that helps them make clinical decisions and save time.
PMID- 10181263
TI - Money management. More hospitals are replacing or upgrading financial systems to
meet changing business demands.
PMID- 10181264
TI - Pioneers assess the role Java can play in health care.
AB - Since Sun Microsystems Inc. introduced Java in 1995, the new object-oriented
programming language has attracted a great deal of attention. While many CIOs
continue to sort the hype from the substance, a handful of health care
organizations are deploying Java-based applications.
PMID- 10181265
TI - Mapping. Using specialized software as a competitive tool.
AB - Cost pressures of managed care, consolidation of health care organizations and
the need to effectively spend marketing dollars are strengthening demand for
geographic information systems. Providers, payers and others are using the
software to convert a wide variety of information into easy-to-understand maps
and reports.
PMID- 10181266
TI - Telemedicine. Secrets to success.
AB - In designing telemedicine programs, developers must carefully assess needs,
select the right technology and figure out how to pay for their programs.
PMID- 10181267
TI - Top 10 trends for pediatrics, children's hospitals, and "kiddiecare" coverage.
PMID- 10181268
TI - Timing is "now" for universal child health insurance.
PMID- 10181269
TI - Children's health today and tomorrow: a millennium outlook.
PMID- 10181270
TI - Merger mania: your case management department can weather the storm.
PMID- 10181271
TI - Train case managers in information technology.
AB - At Hinsdale (IL) Hospital, health information specialists and case managers have
created an innovative training and orientation program to get new case managers
up to speed on the latest tools and techniques in information management.
Established to help clinical case managers better comes to terms with complicated
financial data, the program has grown into a comprehensive training system that
acquaints new hires and old hands alike with the hospital's databases and teaches
them appropriate methods of data mining, collection and usage. The program
consists of a one-and-a-half hour initial orientation, a two-hour follow-up, and
then less formal weekly and monthly meetings held on an ongoing basis.
PMID- 10181272
TI - Kentucky hospital earns rep for continuum care.
AB - At Ephraim McDowell Regional Medical Center in Danville, KY, case managers helped
implement a group of pathways that span the continuum of care by stressing
communication with providers outside the acute care setting. Once patients are
referred to a pathway, the admissions nurse and case manager draw up a schedule
that they share with representatives from the physician's office, rehabilitation,
home health, and related disciplines. At the patient's first scheduled
appointment, each discipline comes to the patient to perform an initial
assessment. Several disciplines also play an active role in preparing for the
patient's discharge, including physicians, social workers, case managers,
rehabilitation services, and home health.
PMID- 10181273
TI - Mother/baby short-stay pathway complements merger.
PMID- 10181274
TI - Understanding JCAHO's latest PI (performance improvement) revisions.
PMID- 10181275
TI - Alternative methods of support empower patients.
PMID- 10181276
TI - Will Medicare provider-sponsored organizations be worth the risk?
PMID- 10181277
TI - Setting up a network is just the first step in managing a PSO.
PMID- 10181278
TI - Network development key to successful Iowa PSO.
PMID- 10181279
TI - PSOs open the door, but alternate strategies may prove more attractive.
PMID- 10181280
TI - Medicare's capitation rates are key to PSO profitability.
PMID- 10181281
TI - Gaining enough market share may be a PSO's biggest challenge.
PMID- 10181282
TI - Compliance programs. Regulatory self-policing seen as important risk-management
strategy.
PMID- 10181283
TI - Physician recruiting. Question recruiters to get the best service in a changing
market.
PMID- 10181286
TI - Medicare PSOs. Task force recommends flexibility for provider-sponsored
organizations.
PMID- 10181284
TI - Corporate culture. Merging cultures key to successful integration.
PMID- 10181285
TI - Mergers and acquisitions. Acquiring a medical network may not be the best
hospital strategy.
PMID- 10181287
TI - Community links help make Medicaid managed care networks work.
PMID- 10181288
TI - Recruitment strategies may blunt impact of emerging allied health shortages.
PMID- 10181289
TI - Balanced Budget Act relaxes Medicaid managed care requirements.
PMID- 10181290
TI - Management service organizations. Choosing the right model can help MSOs succeed.
PMID- 10181291
TI - Behavioral health services: carved out and managed.
AB - This article highlights the financial pressures that led to an examination of how
mental healthcare was provided and paid for, and discusses the rise,
characteristics, and functioning of carved-out behavioral healthcare. The typical
characteristics of managed behavioral health carve outs (MBHCOs), including
contracts, payment arrangements, provider networks, and data collection are
discussed and illustrated using the example of United Behavioral Health. The
article details the function of the MBHCO on cost and utilization, access,
quality, and the relationship of behavioral health services to general medical
care and other human services, but cautions that further research is needed to
evaluate the qualitative aspects of care.
PMID- 10181292
TI - Cancer carve outs, specialty networks, and disease management: a review of their
evolution, effectiveness, and prognosis.
AB - Specialty care programs for patients with cancer were among the first to be
developed, yet they have been some of the slowest to grow or to demonstrate
success. This paper reviews the evolution of cancer carve outs, disease
management, and specialty networks by distinguishing purchasers from sellers on
key attributes. It also describes financing and operational impediments to their
growth and summarizes what little published data there is documenting the success
of these programs. The paper analyzes the critical factors impeding the
development of these cancer programs, and discusses the public policy changes and
health services research that will need to be conducted before the performance
and market influence of cancer carve outs will reach their full potential.
PMID- 10181293
TI - Massachusetts Medicaid and the Community Medical Alliance: a new approach to
contracting and care delivery for Medicaid-eligible populations with AIDS and
severe physical disability.
AB - This paper discusses the origins and experiences of the Community Medical
Alliance (CMA), a Boston-based clinical care system that contracts with the
Massachusetts Medicaid program on a fully capitated basis to pay for and deliver
a comprehensive set of benefits to individuals with advanced AIDS and individuals
with severe disability. Since 1992, the program has enrolled 818 individuals with
either severe disability, AIDS, mental retardation, or general SSI-qualifying
disability. Under a fee-for-service system, these two groups had received
fragmented care. The capitated CMA program emphasizes patient education and self
management strategies, social support and mental health services, and a team
approach to healthcare delivery that has reoriented care to primary care
physicians, homes, and communities.
PMID- 10181294
TI - Special report: mining admissions data. Benchmarking hospital admission rates by
ages.
AB - In this second part of our two-part series on mining hospital admissions data,
Ronald Lagoe, executive director of the Hospital Executive Council, a four
hospital system in Syracuse, NY shows how admissions data readily available from
various state agencies can be analyzed for patterns by age groups. As he points
out below, this information will be particularly valuable as Medicare managed
care takes over. For a discussion of data sources, methodology and analysis, see
part one, beginning on p. 81 of the June Healthcare Benchmarks.
PMID- 10181295
TI - AMAP, JCAHO, and NCQA will coordinate measures.
PMID- 10181296
TI - Vermont moves toward providing plethora of benchmarking information.
PMID- 10181297
TI - Decision-support software eases information flow.
PMID- 10181298
TI - Guideline project tackles middle ear infections.
PMID- 10181299
TI - Wound care: active healing, preventive tactics, and technological breakthroughs.
AB - Recent technological advancements have resulted in healing aids that make wound
care faster and better. Home care providers will want to be in the know about
more active healing practices.
PMID- 10181300
TI - Telehealth and managing congestive heart failure.
AB - Telehealth care is still an emerging technology, but one that provides home care
nurses an excellent way to extend their services. For the patient with congestive
heart failure, a wide range of telehealth care tools are available. By designing
effective telehealth care strategies agencies can save money and still provide
quality care.
PMID- 10181301
TI - Computer information systems in Ohio home care agencies.
AB - Computerized information management is increasingly critical for home care
agencies. Yet little is known of computer capabilities currently available in
home care agencies. Findings from one study indicate that computer support for
clinical services is considerably less developed than for administrative services
and that agencies plan major expansions of computerized clinical support.
PMID- 10181302
TI - The Internet comes to home care.
AB - The Internet can provide home care agencies access to information, patients,
physicians, payors, hospitals, pharmacists, durable medical equipment (DME)
companies--virtually anyone participating in the delivery of care. Agencies that
wish to take advantage of these capabilities need to take a hard look at what
services the Internet can help them deliver.
PMID- 10181303
TI - Consumers' increasing influence on health care.
AB - The individual consumer's new predominance in the health care marketplace is
increasingly influencing policy, strategy, operations, and investment decisions
of health care organizations within all segments of the industry. A recent survey
has some surprising things to say about the consumer's increasingly influential
role.
PMID- 10181304
TI - OASIS. The next 10 years.
AB - OASIS and ORYX are on their way for home care, and those agencies that are not up
to speed on using them may not make it through the next year. Above all, before
implementing OASIS data collection, agencies need to understand outcomes. This
understanding may mean the difference between merely surviving and actually
thriving in home care.
PMID- 10181305
TI - The Joint Commission's ORYX initiative.
AB - Home care organizations and hospices increasingly need to have objective,
quantifiable information about their own performance that they can use externally
to demonstrate accountability. The ORYX initiative will help organizations meet
this need.
PMID- 10181306
TI - True grit. One agency's story.
AB - It's every home care agency's worst nightmare: the feds accuse you of fraud in
Medicare and Medicaid billings. One agency refused to knuckle under--and managed
to survive the ordeal with its integrity intact.
PMID- 10181307
TI - Better training for less money--from outer space.
AB - Agencies that wish to develop innovative, interactive and entertaining inservices
for their employees may want to look at the Alabama Department of Public Health's
program, which has developed cost-effective inservice training for more than
6,000 employees working at 120 sites across the state. It works by using
satellite technology--rocket science to bring the caring touch closer to home.
PMID- 10181308
TI - The Angel Foundation--making wishes come true for terminally ill adults.
AB - Who says wishes don't come true? One home care and hospice agency has been
playing fairy godmother to individuals who suffer terminal or life-threatening
illnesses. Few such organizations exist for adults. But the Angel Foundation
provides a valuable service that other home care agencies may wish to emulate.
PMID- 10181309
TI - Predicting the future.
PMID- 10181310
TI - One giant leap.
PMID- 10181311
TI - Child's death leads to new medication error policies.
PMID- 10181312
TI - ED policy requires good judgment, common sense.
PMID- 10181313
TI - Deciphering Stark II may test your patience.
PMID- 10181314
TI - HCFA takes a narrow view of incentive plans.
PMID- 10181315
TI - Lower rates of unnecessary appendectomies.
PMID- 10181316
TI - Educate teams to develop the best review criteria. Practice guidelines require
planning.
PMID- 10181317
TI - Health care's future? Look to the past.
AB - Although health care is changing, and probably always will be subject to change,
there are certain basic themes present at the founding of the U.S. health care
system that remain important today. Although these themes could be seen as
working against each other, proper attention to both might lead to a "marriage"
that could optimize the system and provide, if not a solution, at least a
workable system for health care.
PMID- 10181318
TI - Facing the staff after a reduction in work force.
AB - The literature is relatively silent on how managers should deal with a reduction
in force (RIF). One difficulty is dealing with the "surviving" staff and
maintaining credibility. It is important to assess the organizational climate and
plan and carry out a forum for the remaining staff. It is especially important to
consider the psychologic effects of staff reduction, which include a sense of
loss of control, hostility, and a tendency to want to find fault or blame. Lack
of attention to these matters can lead to a RIF that compromises the work
effectiveness of the organization by reducing the dedication of surviving members
of the organization.
PMID- 10181319
TI - Helping staff cope with change.
AB - Change seems to be the one constant in health care. This article examines how
employees react to change and provides guidelines to help them and managers
overcome barriers to change. These guidelines include providing support during
change, using appropriate interventions, helping staff find the challenge in
change, helping them find the stamina for change, and fostering teamwork.
PMID- 10181320
TI - Humor: no materiel manager should be without it.
AB - Humor has the potential to be positive or negative, character building or
destructive. Many suggest that a sense of humor is necessary for good health,
whether of an individual or an organization. This article presents ways in which
managers can foster a "laughing with" (instead of "laughing at") attitude as a
means of managing stress, enhancing teamwork, and maintaining employee
satisfaction in the face of adversity.
PMID- 10181321
TI - Literacy: a problem that managers must handle.
AB - Patient and employee illiteracy is a problem that health care managers must deal
with. More than half of all Americans may be unable to read and understand
written materials used in hospitals, clinics, and other health care facilities.
There is a mismatch between employees' and patients' reading level and the
reading level of most written materials used by health care facilities. This can
lead to noncompliance with treatment, missed appointments, wrong dosage of
medications, uninformed consent, and undo fear among patients. Employees who are
unable to read directions or policies and procedures are not able to do their
jobs efficiently. There are things that managers can do to make written materials
more user-friendly.
PMID- 10181322
TI - Self-directed work teams: the wave of the future?
AB - Although teams are currently a popular means of solving work force needs in
health care, there has been little use of self-directed work teams--autonomous
units without a front-line manager and empowered to control their own work. This
article analyzes key differences between self-directed work teams and traditional
teams, looks at three cases in which self-directed work teams were implemented,
and discusses some of the barriers to the formation and use of self-directed work
teams.
PMID- 10181323
TI - Trends in multiculturalism in health care.
AB - Materiel managers are faced with a shrinking world and changing work environment.
The needs and expectations of the customer have shifted because of the increasing
number of multicultural groups. These groups will continue to assert their right
to culturally sensitive care. Materiel managers also need to learn to support and
enhance the skills of a multicultural work force. One important tool for change
will be technology. However, technology that brings the world closer together
also creates new challenges for managers, who will have to deal with
multicultural colleagues, buyers, sellers, and manufacturers of goods and
services.
PMID- 10181324
TI - The effect of holism on the health care system.
AB - Despite controversy over its scientific basis, the holistic health movement is
having a tremendous impact upon society. With the establishment of the Office of
Alternative Medicine within the National Institutes of Health, needed research
will provide data to support the validity of various alternative modalities. A
growing number of physicians will incorporate the philosophy of holistic health
into the current medical model, with some choosing to treat clients with
alternative modalities. Finally, consumer demand will lead to an increase in
third-party reimbursement for alternative medical treatments.
PMID- 10181325
TI - Who will be a good employee in the future?
AB - This article examines the attributes necessary for the successful employee in the
future. Many of these are already familiar to the manager: flexibility and
adaptability, a team approach, and the ability to see the bigger picture.
Implications for the educational process and its development of successful
employees are also presented.
PMID- 10181326
TI - Hospital ethics committees and the future of health care decision making.
AB - In an era of increased patient decision making and limited resources, the solving
of ethical dilemmas requires more than the traditional top-down approach. This
article examines the use of ethics committees in hospitals located in Alabama. A
significant minority of the hospitals do not have committees, despite increasing
calls for ethics committees in the literature and by regulatory and accreditation
agencies. The article also describes the typical composition of a hospital ethics
committee as well as the means by which hospitals without committees solve
ethical problems.
PMID- 10181327
TI - Emergency medical technicians: is career satisfaction within their control?
PMID- 10181329
TI - The health administration internship: a partnership for progress in health
administration education.
PMID- 10181328
TI - Caring for the uninsured in Massachusetts.
PMID- 10181330
TI - Electronic medical records: the future--at some point.
PMID- 10181331
TI - Corporate compliance plans: building the bridge to a well-managed future.
PMID- 10181332
TI - Nontraditional medical treatments grow in popularity as patients and healthcare
organizations find new arrangements.
PMID- 10181333
TI - Primary care groups. Staff's counsel.
AB - Staff are concerned that the establishment of primary care groups may lead to
more direct employment of community staff by GPs. PCTs will have to control staff
resources if they are to plan services of maximum benefit to patients. As primary
care trusts develop, practice staff should be given the option of transferring
their employment to the trusts. Regional clearing house arrangements should be
established to assist the redeployment of NHS and fundholding staff displaced by
the establishment of PCGs.
PMID- 10181334
TI - A woman of no importance?
PMID- 10181335
TI - Using risk assessment to evaluate adverse selection under capitated contracts.
AB - Most provider organizations rely on health plan or market-based information about
capitation rates, per member per month costs, and utilization trends to benchmark
their performance. However, these statistics can be misleading because of
differences in enrollee mix and contracting terms across provider organizations.
This article describes the limitations of health plan contract provisions in
protecting against adverse selection. It describes various actuarial and
statistical data sources for evaluation of adverse selection. The article then
presents various approaches to risk adjustment on population basis and their use
in quantifying adverse selection for health plan contract negotiations.
PMID- 10181336
TI - The use of an integrated clinical laboratory and pharmacy diabetes database to
provide physician performance feedback in an IPA-model HMO.
AB - The ability to link pharmacy claims and clinical laboratory result databases in a
managed care setting holds great promise as an outcomes management tool. The
authors have created a powerful disease management capability that generates
dynamic, disease-specific reports containing actionable, provider-patient-level
laboratory and pharmacy information. This system is used to send reports to
primary care physicians in an independent practice association (IPA)-model
managed care setting to improve the care of patients with diabetes mellitus. This
systematic feedback methodology can augment physician decision-making behavior,
promote compliance with national guidelines, and measure improvement in plan
level, population-based outcomes over time.
PMID- 10181337
TI - Validation of claims diagnoses and self-reported conditions compared with medical
records for selected chronic diseases.
AB - This article assesses the validity of ambulatory administrative and encounter
data and patient self-reported information compared with information contained in
the ambulatory medical record for 17 chronic diseases. Using a sample of 213
adults (18 to 64 years old) and seniors (65 years and older) enrolled in a health
maintenance organization and receiving care at multispecialty group practice in
Minneapolis, Minnesota, sensitivity and specificity for claims and self-report
were calculated for each chronic condition using the medical record as the
criterion standard. The analysis was performed first by blinded review and then
repeated with an unblinded review.
PMID- 10181338
TI - Black-white differences in health perceptions among the indigent.
AB - Two studies were conducted that assessed health perceptions and functional health
status among an urban, low-income population in the southeastern region of the
United States. The first study was conducted with 176 hospitalized indigent
patients prior to discharge from a county hospital. Patients were administered
the Short Form-36 (SF-36) health status questionnaire and two additional
questions regarding perceptions of health. The second study was conducted in the
same geographic region with a nonhospitalized, low-income population. The SF-36
was administered by telephone to 546 randomly selected interview respondents. The
results demonstrated consistent differences between black and white respondents
in referents for self-perceived health. It is suggested that health expectations
and perceptions may be indicative of the cultural, contextual, and social
political factors that affect the lives of this urban, low income population. The
validity of global single-item health indicators for use among low-income
populations is questioned. Further research is needed to develop patient-based
measures that accurately reflect the meanings and values of low-income patient
groups.
PMID- 10181339
TI - Health recommendations by interest group.
PMID- 10181340
TI - The influence of the mass media on the selection of physicians.
AB - The purpose of this study was to examine now media sources influence an
individual's reported choice of a physician as compared to personal referral
sources and how consumers use the Yellow Pages to search for health care
information. A random sample of 762 residents was systematically selected from
the Charlotte, North Carolina White Pages and was asked to participate in a 20
item descriptive phone survey designed and tested by the investigator. Five
hundred and seventy-eight individuals completed the survey, with a response rate
of 75.9%. This study supports previous research suggesting that personal
referrals are the most influential sources in selecting health care services.
Therefore, satisfying and delighting the physician's/practice's existing client
base may be one of the most potent advertising resources at hand. Mass media
sources played a relatively minor role in influencing provider selection in this
study. Nevertheless, it should not be dismissed in as much as the media may be an
important way for physicians to promote "brand recognition," a problem not
considered in this study. Finally, approximately 28% of the participants were
"Yellow Pages users"; that is, individuals who tended to be heavy users of the
Yellow Pages and used it for multiple information-seeking tasks. The findings
related to the Yellow Pages suggest that while it may be useful to advertise in
the Yellow Pages, a more modest financial allocation to this source may be
considered.
PMID- 10181341
TI - Integrating population health concepts, clinical guidelines, and ambulatory
medical systems to improve diabetes care.
AB - The integration of clinical guidelines with office systems has great potential to
improve population health. This article shows how simple office systems can be
developed and applied to expand the impact of clinical guidelines on the health
of populations of patients enrolled in managed care organizations, using diabetes
as an example. The basic tools needed to improve population health include (1)
clinical guidelines that clearly articulate important and specific health goals;
(2) a clinical database that can identify patients who are eligible for guideline
recommended care, monitor this group of patients, and classify patients who need
different levels of intervention; and (3) clinics that are organized in a way
that facilitates provision of guideline-directed clinical care based on cues from
the clinical database. This article illustrates a successful application of this
strategy to improve the care of a population of patients with diabetes enrolled
in health maintenance organization-owned clinics.
PMID- 10181342
TI - Is your waiting room a practice builder--or a holding pen?
PMID- 10181343
TI - Being sued is no excuse for violating confidentiality.
PMID- 10181344
TI - Keeping close tabs on your retirement plan?
PMID- 10181345
TI - Managed care. Maybe patients don't hate gatekeeping so much, after all.
PMID- 10181346
TI - Tax-exempt hospitals sweeten the doctor's pot.
PMID- 10181347
TI - Will the Feds really conclude many doctors are crooks?
PMID- 10181348
TI - Will patients find out all about you on the Internet?
PMID- 10181349
TI - Straight talk from the AMA's new president. Interview by Jeff Forster.
PMID- 10181350
TI - How hard should you be working?
PMID- 10181351
TI - Remapping career paths in a rural laboratory.
PMID- 10181352
TI - Practical strategies for refocusing your career.
PMID- 10181353
TI - Ethos and the laboratory leader.
PMID- 10181354
TI - What's bugging providers. Coalition calls for manufacturers to disclose Y2K
status.
PMID- 10181355
TI - AHA uses focus groups to test reform.
PMID- 10181356
TI - FPA empire crumbling. PPM faces contract cancellations and cash crunch.
PMID- 10181357
TI - Extending the ADA to HIV. High court rules afflicted workers are covered by act.
PMID- 10181358
TI - Humana HMO's marketing attacked.
PMID- 10181359
TI - Donations heating up. Managed-care debate has healthcare organizations opening up
their wallets.
PMID- 10181360
TI - Working toward a full recovery. Hospital CEO gets crash course in crisis
management after boy's death.
PMID- 10181361
TI - Performance payback. Survey shows most execs must hit bonus targets to maintain
total pay.
AB - More than ever, hospital executives are being judged, and paid, based on
performance, a hurdle most of them are making, according to a compensation survey
by Hewitt Associates. Meanwhile, system managers, who are more experienced with
being paid this way, are having a harder time meeting performance benchmarks. The
survey includes 241 healthcare organization respondents.
PMID- 10181362
TI - Alternatives available. Appeals court upholds Washington state mandate.
PMID- 10181363
TI - Help from a friend. Expert systems offer mammogram 'spell checker'.
PMID- 10181364
TI - On a record pace. Tax-exempt bond issues top $17 billion in first half.
PMID- 10181365
TI - Finance company adds new healthcare REIT.
PMID- 10181366
TI - Achieving efficiencies in patient accounts receivables electronically.
PMID- 10181367
TI - Hospitals' funds liquidity improving.
PMID- 10181368
TI - AIDS: no more silver bullet.
PMID- 10181369
TI - The dangers of self-dosing.
PMID- 10181370
TI - Fibrin sealant: an evaluation of methods of production and the role of the blood
bank.
AB - Blood banks can prepare fibrin sealant by several methods. Allogeneic components
allow for banking of the fibrinogen concentrate for immediate use. Autologous
components eliminate the risk of transfusion-transmitted disease to the
recipient, but not necessarily to the preparer. Ethanol and ammonium sulfate
precipitation of fibrinogen concentrate allow use of autologous blood and fast
preparation (less than 90 minutes). Cryoprecipitation from liquid plasma is
adequate, conserving fresh frozen plasma. Cryoprecipitation by the "freeze-thaw"
method has been reported to have the highest fibrinogen yield (7840 mg/dL +/-
1800 mg/dL), whereas ammonium sulfate precipitation has been reported to have the
highest bonding strength (41 g/cm2 10 minutes after thrombin addition). Cost,
storage, preparation time, and transfusion-transmitted disease all play a role in
choice of method.
PMID- 10181371
TI - Fibrin sealant in vascular surgery: a review.
AB - Fibrin sealant (FS) is a mixture of concentrated fibrinogen and thrombin that
creates a fibrin matrix that is slowly degraded by the body's fibrinolytic
system. FS is currently being used in the clinical arena for many applications.
Perhaps the most relevant indication for vascular surgeons concentrates on FS's
hemostatic properties. Current research in many centers is investigating FS's
capability to incorporate drugs and cytokines into the fibrin matrix for slow
release as a drug delivery system for future clinical use. This review will focus
on three main uses of FS: as an anastomotic sealant, as an antibiotic coating,
and as an agent for endothelialization of grafts.
PMID- 10181372
TI - Fibrin sealant in breast surgery.
AB - Recent research has investigated the use of fibrin sealant (FS) in axillary lymph
node dissections performed for staging carcinoma of the breast. The majority of
complications of axillary dissections in breast surgery stem from the two factors
that influence the formation of seromas, hematomas, and lymphedema: the oozing of
small transected vessels and the creation of a reservoir due to the removal of
tissue. An effective surgical adhesive could improve hemostasis and tissue
adherence, thereby decreasing the frequency of these postoperative problems. This
paper reviews the use of fibrin sealant in breast surgery to reduce postoperative
serous drainage by improving hemostasis and tissue adherence.
PMID- 10181373
TI - Fibrin tissue adhesive in otolaryngology-head and neck surgery.
AB - In otolaryngology-head and neck surgery, fibrin tissue adhesive (FTA) is
primarily used for fixation of tissues, for attaining hemostasis, or for drug
delivery. It can be used for positioning implants or ossicles in the middle ear
or as a sealant in closure of cerebrospinal fluid leaks. FTA is an excellent
hemostatic agent and can be used for controlling capillary bleeding along the cut
surface of muscle or in a previously operated site. As a delivery system, FTA can
be used to administer antibiotics, chemotherapeutic agents, or growth factors.
New technology is providing safer homologous products, stronger autologous
products with higher fibrinogen levels, and better applicators.
PMID- 10181375
TI - Tissue adhesives in cardiovascular surgery.
AB - Tissue adhesives are increasingly being used in cardiovascular surgery as
adjuncts to obtain more rapid hemostasis, as tissue reinforcing agents, as
carriers for prolonged local release of antibiotics, to spatially fix long
saphenous vein grafts that could otherwise possibly kink, and to promote
endothelialization of prosthetic graft surfaces. The available tissue adhesives,
their current indications for use, and possible future trends are discussed.
PMID- 10181374
TI - Fibrin solutions to control hemorrhage in the trauma patient.
AB - Fibrin sealant has been used by a variety of surgical subspecialties as a
biological adhesive, sealant, and hemostatic agent. The advantages of these
fibrin solutions make them ideal adjunctive hemostatic agents for patients with
intra-abdominal solid organ injury. Control of hemorrhage from large stellate
wounds of the liver and splenic salvage has been documented in the literature by
surgeons from Europe and the United States. Due to the unavailability of a
commercial product, surgeons in the United States have had to rely on blood bank
produced fibrin sealant. The purpose of this review is to describe research
directed towards developing and evaluating fibrin solutions, both commercial and
blood bank-produced, for hemostasis of injuries to the liver and spleen.
PMID- 10181376
TI - Assessing efficiency in general practice: an application of data envelopment
analysis.
AB - As with any health care process, the efficiency with which outputs are produced
in general practice is of considerable importance. Using data from Lincolnshire,
this study utilizes data envelopment analysis to examine the relationships
between practice costs and outputs, measured not only as the number of patients
treated, but also on the basis of performance indicators. The technique permits
the construction of an efficiency ranking, facilitating the accurate targeting of
monitoring resources.
PMID- 10181377
TI - The causes of variations in unit labour costs: a preliminary study.
AB - This paper reports a study of eight National Health Service Trusts, using data
drawn from the Unit Labour Costs database and supplementary data collected for
the purposes of the study, which set out to begin to explain the large variations
in unit labour cost that exist. On the basis of extensive discussions within and
between units, it was found that major causes of variations in productivity
related to length of stay and bed utilization, which were in turn a result of
variations in case mix. Staff utilization was a further major factor. Another
observation was that the quality of data, particularly the integration of
financial, activity and manpower data, was often poor.
PMID- 10181378
TI - Rational rationing?
PMID- 10181379
TI - A study and comparative analysis of effective and ineffective leadership skills
of physician and non-physician health care administrators.
AB - This paper explores and compares, at both micro and macro levels, the leadership
skills of effective and ineffective managers in a health care setting. In
addition, it compares the leadership skills of physician and non-physician health
care administrators at both levels. The results indicate that effective managers
have significantly different leadership skill profiles than ineffective managers.
Furthermore, effective managers have a more complete set of skills and are not as
likely to rely on one type of skills as the ineffective managers. In addition, no
substantial evidence was found to support prior assertions that physician
administrators would be deficient in leadership skills.
PMID- 10181380
TI - Impact of IT on health care professionals: changes in work and the productivity
paradox.
AB - Health care organizations are under increasing pressure to become more efficient
while at the same time maintaining or improving the quality of care. Information
technology (IT), with its potential to increase efficiency, accuracy and
accessibility of information, has been expected to play an important role in
supporting these changes. We report the impact of patient care information
systems on health care professionals in five community hospitals. The study
framework incorporated both quality of care in Donabedian's elements of structure
process-outcome and Grusec's three levels of IT impact: direct substitution,
proceduralization and new capabilities. The study results suggest that, for
specific tasks, IT increased efficiency and productivity--a single employee was
able to complete more tasks. However, this produced other consequences not
predicted. Participants noted this change did not 'free up time' to spend with
patients, but meant there were potentially more opportunities to provide services
and more tasks to complete. Other effects included: reduced job satisfaction as
more time was spent on the computer; less frequent interactions with patients and
for shorter duration; and an increasingly 'visible' accountability as performance
was easily monitored. There were also changes in roles and responsibilities as
the computer enabled tasks to be carried out from a number of locations and by a
variety of personnel. When innovations are introduced into organizations there
are both expected and unexpected consequences. Increased awareness of the
interactive relationship between computer users and the technology helps
organizations better understand why results do, or do not, occur. One must look
beyond just simply increasing productivity by replacing manual tasks with
automated ones, to examining how the changes influence the nature of work and
relationships within the organization.
PMID- 10181381
TI - A strategic information system to facilitate the use of performance indicators in
hospitals.
AB - Hospital management teams receive voluminous data from a wide variety of sources,
but are unable to distill the essential data they require to make good decisions.
We have used a methodology which helps teams define and use important management
data coupled with an information system that makes this data accessible. Results
of our evaluation indicate that the process of developing a balanced scorecard
(BSC) indicator system helps management teams to define meaningful strategic
objectives and measurable performance indicators. The framework combined with the
information acts as an integrating force, providing a shared understanding of the
unit's goals. We conclude that a customized decision support system which
integrates multiple measures in a BSC framework is a powerful tool for enabling
complex decision making by a management team.
PMID- 10181383
TI - Designing new services in health care organizations: a step-by-step methodology.
PMID- 10181382
TI - Patient-centred performance monitoring systems and multi-agency care provision: a
case study using a stakeholder participative approach.
AB - We describe the processes involved in the development of an information system
which can assess how care given by a number of agencies could be monitored by
those agencies. In particular, it addresses the problem of sharing information as
the boundaries of each agency are crossed. It focuses on the care of one specific
patient group--the rehabilitation of elderly patients in the community, which
provided an ideal multi-agency setting. It also describes: how a stakeholder
participative approach to information system development was undertaken, based in
part on the Soft Systems Methodology (SSM) approach (Checkland, 1981, 1990); some
of the difficulties encountered in using such an approach; and the ways in which
these were addressed. The paper goes on to describe an assessment tool called
SCARS (the Southampton Community Ability Rating Scale). It concludes by
reflecting on the management lessons arising from this project. It also observes,
inter alia, how stakeholders have a strong preference for simpler, non-IT based
systems, and comments on the difficulties encountered by stakeholders in
attempting to reconcile their perceptions of the needs of their discipline or
specialty with a more patient-centred approach of an integrated system.
PMID- 10181384
TI - UPHS Health System (University of Pennsylvania Health System) revises quality
management function.
PMID- 10181385
TI - A formula for failure.
PMID- 10181386
TI - Off the couch and on the job.
PMID- 10181387
TI - What you'll need to get ahead.
PMID- 10181388
TI - When cancer comes to work.
PMID- 10181389
TI - Corporate health gets creative.
PMID- 10181390
TI - For-profit or not. Where's the best care?
PMID- 10181391
TI - Datawatch. Who would reform managed care?
PMID- 10181392
TI - Aging policy for a diverse population: a symposium.
PMID- 10181393
TI - Managed care and assisted living: trends and future prospects.
AB - With its emergence as a new, residential long-term care option, more than half of
the states have established policy on assisted living. In 1996, over 30 states
had created a state licensure category or passed legislation authorizing
development of regulations. Known primarily as a resource for wealthy elders
needing assistance with activities of daily living and health care needs,
assisted living is increasingly being covered as a service under state Medicaid
programs. Assisted living is widely seen as a resource for managed care
organizations enrolling Medicare beneficiaries. Flexible capitation payments and
incentives to substitute services create opportunities for assisted living
facilities and HMOs to form partnerships. Enrollment of beneficiaries in Medicare
HMOs has reached 4.5 million and is growing over 30% a year. In addition, state
Medicaid agencies are developing programs to enroll elders, most of whom are also
Medicare beneficiaries, in managed care programs that include long-term care. The
move toward managed care and the increasing interest in integrating acute and
long-term care for dual eligibles signals a growing role for assisted living
facilities as a major resource for elders who need a supportive and service-rich
residential living environment.
PMID- 10181394
TI - Analysis of comfort care for the terminally ill: the hospice approach.
AB - Much of the published literature on hospice care focuses on a single dimension of
this increasingly popular approach to meeting the needs of the terminally ill. By
contrast, this article takes a broader view by examining the hospice concept and
its implementation through the lens of the nine dimensions of the SEPTEMBER model
-focusing in turn on each of the social, economic, political, treatment, ethical,
managerial, bereavement, education, and research elements. This broader
perspective brings together in kaleidoscopic fashion these diverse but
interconnected elements of hospice care. This integrated conceptual model helps
administrators and health care professionals to develop a clearer overall picture
of the multifaceted challenges involved in delivering palliative care to dying
patients.
PMID- 10181395
TI - Special care units for Alzheimer's patients: their role in the nursing home
market.
AB - The Special Care Unit (SCU) is a new, rapidly proliferating mode of caring for
people with Alzheimer's disease (AD). Approximately 10% of nursing homes within
the U.S. have SCUs with the number expected to grow substantially in coming
years. SCUs are largely unregulated and not uncontroversial. This article
discusses their emergence over time, their origins, growth, and the call for
standardization. Subsequent sections review the range of potential benefits and
costs associated with SCUs, optimally defined as well as research evidence
available on this mode of care. Recent cost-setting and reform pressures in the
nursing home industry are discussed in the final sections along with the likely
future of AD SCUs in this environment.
PMID- 10181396
TI - Goals for Alzheimer's care in nursing homes: what kind of differences do special
care units expect to make?
AB - Special Care Units (SCUs) for people with dementia have been enthusiastically
promoted although many residents with dementia live elsewhere in their nursing
home. In response to open-ended questions during personal interviews,
coordinators of all 64 SCUs in Minnesota nursing homes described their goals and
criteria for success. They then rated the importance of a list of possible goals
and their unit's success in achieving them. Unit coordinators of 173 nursing home
units in facilities with SCUs and 135 units in facilities without SCUs answered
the same questions about people with dementia in their own units. When
unprompted, respondents both in and outside SCUs were varied, sparse (averaging
3.1 goals per person), vague, process-oriented rather than outcome-oriented, and
sometimes unrealistic. Yet, respondents later strongly endorsed most of the 24
goals the researchers suggested. ANOVA and regression analyses revealed few
statistically significant differences according to unit type, although SCU
coordinators were more likely to aspire to fewer medications, reduced disruptive
behavior, and reduced agitation and anxiety, and were less likely to want
residents to sleep through the night. Some differences were only between SCUs and
non-SCUs in facilities without SCUs. Characteristics of facilities, coordinators,
and case mix (e.g., proportion of dementia on the unit) were as predictive of
goals and perceptions of success as SCU units. Findings reinforce the lack of
conceptual clarity about expectations for direct and indirect effects of SCUs.
PMID- 10181397
TI - Epidemiologic transition theory and aging: Hispanic populations of North America
and the Caribbean.
AB - As the forces of social and economic development combine with epidemiological
transitions, population aging will continue to impact world health status and the
provision of health services. Epidemiology provides an interdisciplinary link to
the traditional study of population change by enhancing the demographic
parameters of fertility, life expectancy, and migration, with specific measures
of mortality and morbidity in order better to predict the pace and concentration
of aging within a population. In this article, the authors examine three
theoretical models of epidemiological transition and offer historical (1950-1995)
and projection (1995-2050) data for the development patterns in Cuba, Dominican
Republic, Puerto Rico, and Mexico. They contrast trends in fertility, life
expectancy ratios, and gender differences in these countries with the Hispanic
population of the United States. Central to this study are the cause of death
statistics presented to identify the model occurring in each country. Shifts in
the gender mix at older ages are presented due to the decline in fertility and
death associated with childbearing years and the timing of the transition from
high mortality to infectious disease to high mortality from chronic and age
related disease.
PMID- 10181398
TI - Medicaid policies for the hospice care needed by people with Alzheimer's disease.
AB - This study surveyed the state Medicaid programs and the state affiliates of the
National Hospice Organization to identify Medicaid policies that improve the
quality of hospice care provided to Medicaid recipients with Alzheimer's disease
(AD). Medicaid programs should expand their use of the home and community-based
care waiver programs to include specialized services that allow people with AD to
remain at home and to assist family members with their care. Among these services
are homemaker services, personal care, a range of respite care, home-delivered
meals, and companion services. These waiver programs also allow states to
establish more generous eligibility standards for waiver services, enabling more
people with AD to quality for waiver coverage than would qualify for the
traditional Medicaid program.
PMID- 10181399
TI - Invisible employees. How to deal with excessive absenteeism.
PMID- 10181400
TI - Energy cost control.
PMID- 10181402
TI - Outcomes research. A common sense approach.
PMID- 10181401
TI - Food and nutrition services for the elderly.
PMID- 10181403
TI - Hunger is not about a lack of food. It's about getting food to the hungry.
PMID- 10181404
TI - Dishwashing: current standards and a look to the future.
PMID- 10181405
TI - Tips for writing competency statements. Focus on adults.
PMID- 10181406
TI - Strategic partnership is essential to successful full-risk contract.
PMID- 10181407
TI - Tiptoe toward taking global risk contracts.
PMID- 10181408
TI - Do physicians know what employers really want?
PMID- 10181409
TI - Increase patient base: contract with self-insurers.
PMID- 10181410
TI - PSO notice to providers: Uncle Sam wants you.
PMID- 10181411
TI - Compliance is a million-dollar word. Here's how to get compliance program
started.
PMID- 10181412
TI - Massachusetts PHO offers blueprint for success.
PMID- 10181413
TI - Should your PHO consider forming a PSO?
PMID- 10181414
TI - Health plan finds extra prenatal services not cost effective in treating Medicaid
risk patients.
AB - Good news and bad news about Medicaid prenatal efforts: Although this Minneapolis
HMO didn't reduce overall costs by instituting a comprehensive prenatal program
targeted at high-risk mothers, administrators still say there are clear-cut
benefits to managing this patient population. Here are the results of a two-year
study, plus lessons learned in the effort.
PMID- 10181415
TI - Tap your own Medicare risk members to supply needed social services for peers.
AB - Start a Medicare peer volunteer program to meet your members' social service
needs: For 11 years, Elderplan Inc. has used senior volunteers to effectively and
inexpensively meet the social service needs of its frail and homebound members,
plus gained loads of favorable publicity and community goodwill in the process.
Find out the benefits of such a program and get some tips on how to start one at
your organization.
PMID- 10181416
TI - Data file. Most Medicare plans to see only 2% rate hike in 1999.
AB - Data File: You'll find HCFA's 1999 payment rates for 100 U.S. counties with the
highest Medicare risk enrollment on page 108. Plus, is managed Medicaid losing
its sizzle? A new study finds that declining payment rates and changes in state
programs are driving commercial HMOs out of Medicaid risk. Although this may
signal a market opportunity for Medicaid providers, researchers find that profit
margins can be slim to none.
PMID- 10181417
TI - Study finds managed Medicaid market starting to fizzle.
PMID- 10181418
TI - Invest in data systems to manage your senior patients.
PMID- 10181419
TI - Get a foothold on the cost of diabetes complications.
PMID- 10181420
TI - Comprehensive approach needed for effective management of chronically ill
seniors.
AB - Keeping geriatric patients healthy and out of the hospital can save your
organization big dollars, but it's a task much more easily said than done. In
this "second generation" DM pilot, find out how a broad-based approach that
addresses functional and psychosocial needs, as well as medical issues, may
become the gold standard for disease management in the golden years.
PMID- 10181421
TI - Boost outcomes and slash hospitalization with aggressive approach to
schizophrenia.
AB - Proper care for schizophrenia patients is sorely lacking, leading to high
hospitalization rates and poor outcomes. But a national study now points the way
to better care for the severely mentally ill with specific guidelines for
medication and behavior management. Here's how you can put these strategies to
work.
PMID- 10181422
TI - Mental health provider contracts for intensive community services.
AB - Community treatment is a 20-year-old model of care for patients with mental
illness that is proven effective but rarely implemented. Find out how one
behavioral health managed care provider has partnered with the state of Iowa to
create a community-based team approach for serving the mentally ill and their
families.
PMID- 10181423
TI - Population-based asthma management produces dramatic cuts in ER visits,
hospitalization.
AB - Getting an asthma patient to comply with medication and lifestyle changes
requires more than a one-size fits all strategy. This DM effort produced dramatic
decreases in hospital and emergency room use after implementing a personalized
assessment and goal planning approach in a small Medicaid population.
PMID- 10181424
TI - Assess your program's impact with benchmark performance data.
PMID- 10181425
TI - Close encounters of a canine kind.
PMID- 10181426
TI - EMS: the business of service.
PMID- 10181427
TI - Update to 1998 buyer's guide: new companies, EMS statistics. The silver book.
PMID- 10181428
TI - When tragedy hits paradise. Hurricane Pauline devastates Mexican coast.
PMID- 10181429
TI - Dr. Deming and the event fund-raising process.
PMID- 10181430
TI - Marketing an event: a holistic approach.
PMID- 10181431
TI - Savvy fund raisers are expanding their markets by utilizing mail order buyer
data.
PMID- 10181432
TI - Engaging the faculty: a university science professor recommends getting his
colleagues in deep with fund-raising programs.
PMID- 10181433
TI - On partnership.
PMID- 10181434
TI - Donors want to know where the $$ goes!
PMID- 10181435
TI - Biomedical experimentation involving elderly subjects: the need to balance
limited, benevolent protection with recognition of a long history of autonomous
decision-making. Part II.
PMID- 10181436
TI - Safeguarding health information.
PMID- 10181437
TI - Toward secure health information and the electronic health record.
PMID- 10181438
TI - In the public interest: disclosing confidential patient information for the
health or safety of others.
PMID- 10181439
TI - The Personal Health Information Protection Act, 1997: the police perspective.
PMID- 10181440
TI - A health information statute for Ontario: a consumer's perspective.
PMID- 10181441
TI - Health information and health insurance.
AB - In summary, the need for protection of personal privacy, especially when it comes
to sensitive medical information, should be regulated to prevent unnecessary and
unauthorized dissemination. At the same time, in the interests of optimal patient
care at the least expense, regulations, procedures and technology must be in
place to allow ready access by all professionals having responsibility for
providing and managing this care. In addition, the system must provide for
similar ease and right of access to insurers and their representatives who have
contracted with the client for necessary health benefits.
PMID- 10181442
TI - A tribunal's perspective on Ontario's proposed health information law.
PMID- 10181443
TI - Legislated rights advice: a cautionary tale.
PMID- 10181444
TI - Evaluating predictors and concomitants of patient health visit satisfaction: an
empirical study focusing on methodological aspects of satisfaction research.
AB - We propose that the weak and conflicting results from various studies of
satisfaction concomitants are due to the use of scales which sum scores from
items that measure different types of satisfaction. The hypothesis is clearly
supported, leading to the strong recommendation that different types of patient
satisfaction be studied separately. Implications for studying and potentially
increasing patient satisfaction are discussed.
PMID- 10181445
TI - Factors related to nurse retention and turnover: an updated study.
AB - How to attract and retain hospital registered nurses (RNs) has become a recurring
theme discussed by hospital boards, administrators and physicians in the U.S.
This study seeks to provide current data on this situation. The exploratory
research effort consisted of 13 depth interviews with physicians in a major
metropolitan area in the southeastern U.S. and less formal discussions with six
hospital nurse administrators. The formal research effort involved hand
delivering questionnaires to nurse administrators for distribution to nurses in
six hospitals in the same region. The principle reasons nurses change jobs fall
into four categories: salary or benefits, convenience, work schedule, and job
related stress. After one or more hospital moves the nurses become more
satisfied. Hospital administrators should institute motivational and hospital
commitment programs to improve retention/reduce turnover, e.g., work schedule
rotation, work responsibility rotation, team approaches to health care and
award/recognition programs.
PMID- 10181446
TI - An empirical analysis of consumers' attitudes toward optometrist advertising.
AB - The purposes of this study were to determine: (a) consumers' attitudes toward
advertising by optometrists and (b) whether city of residence, occupation, age,
sex, race, marital status, number of children in household, total family
household income and education accounted for any significant differences in
consumer attitudes toward optometrists that advertise. Information obtained from
this study could be used by optometrists to plan and improve the quality of their
advertising.
PMID- 10181447
TI - The status of TQM in healthcare.
AB - The face of the healthcare industry has changed dramatically over the last few
years. This study examines the literature related to Total Quality Management
(TQM) and Benchmarking (BM) applications in healthcare. Recommendations for
healthcare managers and administrators, as they chart operational and strategic
directions for their organization, are provided. In this context, a conceptual
framework which stresses the significance of viewing the healthcare organization
as an open system is provided. The framework underscores the fact that TQM and BM
efforts should not be viewed in isolation. Rather, these efforts should be viewed
as an integral part of the operational and strategic facets of the healthcare
organization.
PMID- 10181448
TI - The role of healthcare marketing: in the aftermath of the anti-referral movement.
PMID- 10181449
TI - Professional dental services: the yellow pages advertising decision.
AB - Yellow pages advertising decisions are among the most important marketing
decisions made by dental services professionals. Yet, little empirical evidence
is available to guide these decisions. Through a literature review, the purpose
of this article is to synthesize available knowledge in this area and provide
guidelines for more effective yellow pages advertising.
PMID- 10181450
TI - General practice. Situations vacant.
PMID- 10181451
TI - General practice. Building to scale.
PMID- 10181452
TI - General practice. Whine lists.
PMID- 10181453
TI - The NHS at 50. A matter of life and death.
PMID- 10181454
TI - The NHS at 50. Look back in wonder.
PMID- 10181455
TI - The NHS at 50. In the frame.
AB - Photography offers a unique medium for exploring and revealing the complexity of
the health service and the humanity that lies at its heart. The NHS commissioned
a number of photographers to show different areas of healthcare as they are
today. Reproduced here is some of the resulting work, which is included in the
NHS now... towards the future exhibition touring the UK this year.
PMID- 10181456
TI - The NHS at 50. Where would we be without it?
PMID- 10181457
TI - 50 years of the NHS. Bevan's babies at 50.
AB - It was the year of the austerity Olympics in London, the first Polo mint rolled
off the production line, bread was tuppence a loaf, and the NHS was born, along
with 905,000 babies in the UK. Bernadette Friend tracked down some of Bevan's
1948 babies--who went on to work in the service they grew up with--to find out
about their experiences of the NHS and hear their prognosis for its next half
century.
PMID- 10181458
TI - Launch of the NHS. What the papers said.
PMID- 10181459
TI - General management. At your service.
PMID- 10181460
TI - Organizing health care for people with seizures and epilepsy.
AB - The day-to-day responsibilities of managing seizures and epilepsy fall most
heavily on patients and their families. Unfortunately, health care services in
the United States are not organized to identify, diagnose, and treat people with
seizures effectively nor are they delivered in such a way that patients and their
families can engage in a positive, collaborative relationship with health care
providers. This article describes a model of chronic illness care as applied to
seizures and epilepsy, that is, how care should be structured to help people with
seizures live as well as possible.
PMID- 10181461
TI - Treatment of torture survivors: an introduction.
PMID- 10181462
TI - Caring for survivors of torture in an urban, municipal hospital.
AB - Survivors of torture can present with multiple health consequences, both physical
and psychological, which can persist even years after the abuse. The authors
developed a multidisciplinary program in the primary care medical clinic of an
urban municipal hospital in New York City serving an ethnically diverse
population to provide multidisciplinary care to survivors of torture and their
families.
PMID- 10181463
TI - The Indochinese Psychiatry Clinic: trauma and refugee mental health treatment in
the 1990s.
AB - The Indochinese Psychiatry Clinic (IPC), located in Boston, was founded in 1981
to meet the special needs of traumatized Cambodian, Vietnamese, and Laotian
refugees resettling in the Boston area. Over the past 16 years, IPC has pioneered
the field of refugee mental health and the treatment of the psychological and
social sequelae of mass violence and torture. IPC developed the bicultural model
of psychiatric treatment of refugees suffering from trauma-related mental
disorders, which utilizes a multidisciplinary, bicultural team approach that
emphasizes understanding the patient's trauma history within the appropriate
cultural, social, and political context. This article summarizes IPC's
background, patient profile, clinical approach, service elements, and funding
structure. Recent immigration and welfare reform legislation will have a harsh
impact on the population of refugees who are disabled due to the psychosocial
consequences of their traumatic experiences. This legislation and the
restrictions on mental health care imposed by public managed care will also
affect the providers of their mental health care.
PMID- 10181464
TI - Treatment of survivors of political torture: administrative and clinical issues.
AB - Treatment of survivors of political torture is a new field, the symptoms of
survivors are many and difficult, clinicians in general are not experienced in
treatment, and there is little money available. Both administrative and clinical
decisions often must take into account political realities not found in other
treatment environments. To overcome these obstacles has required building an
agency with a small economy, a sense of community among its workers, flexibility
about the presence and pervasiveness of politics, the ability to address
countertransference, and goals that allow workers to cope with the difficulty and
size of the problem of torture.
PMID- 10181465
TI - Can patients with chronic illness have trust in managed care organizations? Yes,
if the rules change.
PMID- 10181466
TI - FQHC (Federally Qualified Health Center): harnessing the incentives of cost
reimbursement.
AB - Community health centers (CHCs) are federally supported primary care providers to
the low-income and uninsured. The federally qualified health center (FQHC)
legislation requires states to pay CHCs for Medicaid services on the basis of
reasonable cost. The statute generated controversy, particularly in a time when,
for most providers, cost-related reimbursement has given way to fixed payments
and managed care. This article examines the impact of FQHC on revenue and
utilization of CHCs, using data for 328 centers that were in continuous operation
between 1989 (the year the legislation was enacted) and 1992, the first year of
full implementation. During this period, the CHCs Medicaid revenue grew rapidly.
FQHC is estimated to account for under one third of the total increase, while
inflation and growth in utilization due to expanded Medicaid eligibility are
estimated to account for the other two thirds. At the same time, the change to
cost-related reimbursement had a significant increase in total service users and
Medicaid recipients receiving care from CHCs. Although some expected that cost
reimbursement would lead to inflationary increase in utilization, this did not
occur. There was no statistically significant relationship between the change in
payment methodology and changes in encounters per user. The experience of FQHC
indicates that, for safety net providers of primary care, cost-related
reimbursement is not "inherently inflationary." Results of this study raise the
question of whether payment within constraints, but bearing relationship to cost,
is not an appropriate approach to developing primary care capitation rates for
these providers--and assuring maintenance of the safety net for the uninsured.
PMID- 10181467
TI - Buying medical technology for ambulatory care.
PMID- 10181468
TI - Managed care: what now?
PMID- 10181469
TI - New survey shows rift between health executives and radiologists.
AB - This report marks International Radiology Group's first annual survey of hospital
administrators and diagnostic imaging department heads. The survey was conducted
to determine how the managers of diagnostic imaging departments at a broad range
of hospitals evaluate the quality and cost effectiveness of their departments. In
particular, the survey addresses how administrators and department heads evaluate
the working relationships they have developed with radiologists affiliated with
their facilities.
PMID- 10181470
TI - The negative impact of MQSA (Mammography Quality Standards Act) on rural
mammography programs.
AB - Since Roentgen's discovery in 1895, physicians and scientists have found ways to
use x-ray to evaluate and diagnose disease. In 1960, Dr. Richard Egan modified an
x-ray machine to image the breast, for example. In 1982, one study found that
deaths from breast cancer could be reduced 40 percent by using screening
mammography. In 1991, Congress appropriated $90 million for breast cancer
research, a figure that rose to $406 million several years later. The Mammography
Quality Standards Act (MQSA), passed in 1992, requires all mammography facilities
to meet minimum quality standards for equipment, radiologists, physicists and
technologists. Regulations require extensive records of medical audit and outcome
analysis, personnel qualification and medical reporting. Inspection and
certification are now the responsibility of the Food and Drug Administration
(FDA). Although they ensure compliance with the law, these inspections cost each
facility $1,549 annually and the average cost to reach compliance with MQSA is
$18,000. These fees are easily absorbed by high-volume centers but are burdensome
for smaller, lower volume centers. Screening exams, to be useful, must be simple,
accessible and cost-effective. MQSA's regulations have added significant costs
and in most cases, the smaller centers will be forced to raise prices or
discontinue offering mammography for a segment of the population with little or
no other recourse for screening. The FDA should look for ways to perform more
cost-effective inspections that still enforce regulations and monitor quality.
Inspections should be unannounced and fines raised for violations. Implementation
costs must be more realistic and the amount of paperwork reduced.
PMID- 10181471
TI - MQSA (Mammography Quality Standards Act) update--focusing on quality assurance.
AB - To have uniform national standards, Congress passed the Mammography Quality
Standards Act (MQSA) in 1992. Screening and diagnostic facilities must now meet
minimum quality standards for personnel, equipment and recordkeeping, and be
certified by the FDA, the federal agency designated to implement MQSA. The FDA is
responsible for developing final standards, approving accrediting bodies,
certifying all mammography facilities in the U.S., evaluating the effectiveness
of the program, and implementing sanctions for noncompliant facilities. Congress
recognized the urgent need for national mammography standards, but realized that
10,000 mammography facilities could not be certified to meet the regulations
before October 1, 1994. President Clinton signed legislation granting the FDA
Interim Rule authority and allowing the FDA to adopt existing standards from the
ACR, HCFA and state regulations. The Final Rules have significant changes in the
Quality Assurance (QA) Sections (900.12 d and e) and indicate where staff must
now conduct, document and evaluate the results of QA tests, taking responsibility
for establishing and maintaining a QA program that ensures safety, reliability,
clarity and accuracy of the mammography services they perform. The Rules also
specify the roles of interpreting physicians, medical physicists and quality
control technologists. Data indicates that such regulation has improved
mammography in the U.S. By January 1997, the Government Accounting Office
reported that 1,500 facilities had undergone two rounds of MQSA inspections.
During the first year of MQSA, 26 percent had significant violations, while only
10 percent did on the second round.
PMID- 10181472
TI - 1998 MQSA (Mammography Quality Standards Act) final rule released. American
College of Radiology.
AB - In October 1997, the Food and Drug Administration (FDA) released the final
regulations for implementing the Mammography Quality Standards Act (MQSA).
Briefly, the final rule establishes experience requirements for medical
physicists and radiologic technologists and clarifies equipment standards. The
Interim Rules, issued in late 1993 and amended in 1994, now apply. Final
regulations become effective April 1999, with certain equipment regulations
becoming effective in October 2002. Changes in experience and continuing
education requirements for medical physicists and radiologic technologists
parallel requirements in the interim rule. The FDA shifted the majority of
quality assurance requirements for equipment to the quality assurance section of
the regulations, and will treat them as performance standards. Under the final
rule, each facility is required to have a system to ensure that mammogram exam
results are communicated to patients in a timely manner. Under the interim
regulations, mammography facility personnel must continue to participate in
medical education programs in mammography to acquire five CME/CEU per year.
PMID- 10181473
TI - Top ten reasons to go through a survey.
PMID- 10181474
TI - Strength through sharing: interdisciplinary teamwork in providing health and
social services to northern native communities.
AB - The delivery of health and social services in Canada's northern First Nations is
undermined by the fact that professionals from outside and para-professionals
from the communities often fail to respect one another's capabilities or to
understand one another's roles and, consequently, do not work well together. This
paper explores the personal, professional, and situational causes, using examples
of mental health care in the Sioux Lookout Zone of northwestern Ontario. Arguing
that an interdisciplinary team approach is the ideal and, perhaps, the only real
way in which essential services can be delivered, the authors suggest ways to
achieve more effective collaboration.
PMID- 10181475
TI - Improving mental health services for urban First Nations: policy issues relevant
to health care reform.
AB - This paper discusses issues related to the development of plans to improve the
effectiveness of mental health services for urban First Nations people. The
discussion focuses on emerging issues related to health care reform and
regionalization. While it is impossible to make specific recommendations without
reference to local conditions, developing an awareness of the general issues
involved will help in the process of identifying the principles and approaches
needed to frame local solutions.
PMID- 10181476
TI - What makes us strong: urban aboriginal perspectives on wellness and strength.
AB - The limitations of a needs orientation for aboriginal mental health planning are
evaluated in terms of the discrepancy between First Nations and western medical
paradigms of health. We propose an alternative approach that focuses on how
aboriginal people conceptualize wellness and describe their strengths. This
provides a focus for initiatives that promote well-being by enhancing strengths
rather than concentrating solely on deficits. We illustrate this approach by
highlighting the indigenous knowledge of urban First Nations people in
Vancouver's Downtown Eastside neighbourhood. We conclude that supporting existing
strengths promotes wellness in holistic, culturally appropriate, and empowering
ways.
PMID- 10181478
TI - First Nations counsellor training in British Columbia: strengthening the circle.
AB - First Nations people in British Columbia are struggling to overcome the effects
of assimilationist practices and cultural loss. Many of the mental health
problems facing First Nations people today can be traced to this loss. Their
communities believe the best way to address this problem is by training their own
people as mental health professionals who could then provide informed and
culturally relevant counselling services. In the spring of 1996 a province-wide
survey was conducted to determine the nature of counsellor training needed by
First Nations people in the province of British Columbia. This article describes
the rationale for this survey and the results.
PMID- 10181477
TI - Healing experiences of British Columbia First Nations women: moving beyond
suicidal ideation and intention.
AB - This study explores how five British Columbia First Nations women moved through
suicidal ideation and intention in their youth. Much of their healing process was
facilitated by a reconnection to their cultural identity and traditional native
spirituality. Phenomenological research methods were used to guide the interview
process, analysis, and the interpretation of unstructured interviews. Each
transcribed interview was analyzed for themes and developed into a narrative.
Several procedures were used to examine the validity of the analysis and
interpretation, including participant review of the findings. Three of the 12
themes that emerged suggest common experiences surrounding suicide attempts or
ideation. These experiences suggest that the impact of separation from family,
community, and culture was significant for each of these women. Nine of the 12
major themes describe a variety of healing experiences for these five women,
involving elders or other role models, professional counsellors, family, and
community. As a consequence of their healing experiences, all participants
reported an increased sense of personal empowerment, a positive view of
themselves, and a commitment to a positive future for themselves and other First
Nations people. The significance of cultural connections and native spirituality
may have important implications for the intervention and prevention of suicide in
First Nations youth.
PMID- 10181479
TI - MediCal devises pay policy for California telemedicine consults.
PMID- 10181480
TI - Texas kicks into high gear with reimbursement, lone star state is ready for road
test.
PMID- 10181481
TI - It's time for organized medicine to carry telemedicine's banner.
PMID- 10181482
TI - Moving forward, looking back: telemedicine in the year ahead.
PMID- 10181483
TI - Hybrid business models rely on out-of-the-box thinking.
PMID- 10181484
TI - MCG and Georgia Tech attract partner for commercial venture.
PMID- 10181485
TI - Telemedicine supports primary-care delivery at outlying VA centers.
PMID- 10181486
TI - The clinical services manager: a curriculum for the 21st century.
AB - The dynamism of change in the evolution of integrated health-care systems is
driving change in the skills and competencies required to manage diagnostic
services. Formal educational preparation and practical experience in a wider
array of disciplines will be essential to the backgrounds of those who will be
chosen for these new and ever more complex roles. Curricular elements relevant to
this educational challenge are outlined herein. This article is intended to
expand on the position of CLMA as reflected in the position paper "New Path for
Health-Care Leadership: Clinical Systems Management," issued in August 1997 (1).
PMID- 10181487
TI - Performance and retention of professional employees who work in teams: the
effects of commitment and support.
AB - The purpose of this study was to determine the impact of support and commitment
on job performance and turnover intentions of professionals working in a team
environment. As hypothesized, the results indicated that job performance was
influenced positively by both professional and team commitment as well as by
perceived organizational and team support. Intention to quit the organization
went down as organizational support and commitment went up, and intention to
leave the profession similarly was related to team support and commitment
Interestingly, professional commitment had a deleterious effect on intention to
quit the organization, whereas organizational support had a positive effect on
professional commitment.
PMID- 10181488
TI - Timeliness and best demonstrated practices.
AB - Significant changes have occurred in many hospital-based laboratories over the
past few years. The demands from the medical staff to deliver the highest quality
test results in the shortest possible time coupled with the mandates from
hospital administration to become cost efficient have given laboratory managers
many challenging opportunities. Information management is a basic component of
the process required to meet the timeliness goal. Best demonstrated practices for
the various sections within our laboratory resulted when combining five
components of daily management. These are instrument automation, using a
laboratory information system to auto-merge and auto-release tests, consolidating
workstations, redistributing work among the technical and nontechnical personnel,
and implementing key indicators to follow improvement.
PMID- 10181489
TI - Reengineering the mind, career, system, department.
AB - In 1993, Hammer and Champy inspired many health-care institutions to initiate
reengineering projects with their prediction that America's largest corporations
would fail if they did not apply the principles of business reengineering. Many
of these companies reengineered to simplify their processes but did not achieve
radical gains. Who or what is to blame for the failures? Does health care's
complexity play a role in these failures? A 1981 study found that health care is
more than 2,000% more complex than the standard business. It concluded that
"routine" management strategies do not provide a sufficiently comprehensive
theory for managing health care's complexity. This article addresses the need to
reengineer on four levels--the mind, career, system, and department--to
circumvent these complexities. Reengineering on each level enhances the chances
for success on the other levels. In today's tumultuous health-care environment,
you need to understand your role in reengineering at each level so you can
implement it, support it, and live it. If you succeed, you will achieve radical
gains, add a valuable tool to your repertoire, enhance your self-confidence, and
become a leader in the industry.
PMID- 10181490
TI - Recent trends in clinical laboratory automation.
AB - A convergence of concepts has allowed clinical laboratory automation to proceed
in a greater number of laboratories: developing automation control interfaces,
direct track sampling, and adopting a universal interface. The laboratory
automation system (LAS) must interface to the laboratory information system
(LIS), which provides the information necessary for routing and scheduling and
for future rules-based processing, an important component of the LAS. The
automation system also must operate in a real-time or near real-time environment
and use the single tube per carrier paradigm. LAS capabilities should span the
clinical laboratory and run parallel to the LIS with respect to information flow.
The laboratory automation software will control the automated technology and the
transportation system that binds clinical laboratory instruments together. It
must be able to both drive the hardware components and interface with patient
information sources, and it should further the goals of the health-care delivery
system by supporting outcomes optimization and utilization management of
laboratory resources. The development of workcells based on disciplines such as
chemistry or hematology is having and will continue to have a significant effect
on the acceptance of clinical laboratory automation technologies.
PMID- 10181491
TI - Management strategies for encouraging creativity.
AB - Change, chaos, and uncertainty touch every part of every institution. The
laboratory is not immune. Managers content to continue on their familiar path
soon will find themselves bypassed. To meet today's challenges, directors of
technical operations, laboratory directors, team leaders, and coordinators need
plenty of creativity--from everyone on their staff. It is no longer just "nice"
to improve group output and problem-solving skills while staying within a
"shoestring" budget. It is absolutely necessary. In this article, we explore
strategies laboratory managers can use to tap the creative potential and
commitment of their people. These strategies work. Whether it involves using
humor, creating "idea centers," or "deconstructing the bureaucracy," the goal is
the same: to encourage clinical managers to think beyond their technical and
managerial experience. The examples in this article may not suit the needs,
situations, or tastes of all laboratory managers. They are "food for thought."
The concepts and strategies these examples illustrate are every laboratory
manager's keys to adapting successfully to future challenges.
PMID- 10181492
TI - As we see it. A savory mix: multidepartmental management.
PMID- 10181493
TI - Power planning, accelerated implementation, and orchestration management.
AB - Staggering adjustments are being demanded in the medical world. New laws,
regulations, technology, and competition are forcing decision makers to adopt new
approaches relating to how they manage their institutions. This article discusses
an organized program that employs an array of management tools and techniques
that can be of great value to those who are embarking on a program of deliberate
methods change.
PMID- 10181494
TI - And they do it their way!
PMID- 10181495
TI - www.healthcare. What's your hospital's address? Not street address--website
address.
PMID- 10181496
TI - Alabama hospitals make presence felt on the Internet.
PMID- 10181497
TI - What's the plan? A look at the State of Alabama's health planning process.
PMID- 10181498
TI - Population-based information systems provide benchmarks needed to manage
capitated contracts.
PMID- 10181499
TI - Corporate America is looking beyond health plans to develop benchmarks for
medical groups. Here's what GM has in mind.
PMID- 10181500
TI - Investors look for systems that will be around long enough to pay off their debt.
They use traditional financial benchmarks.
PMID- 10181501
TI - What are the benefits of preventive health care?
AB - In most forms of evaluation the benefits of preventive health care are narrowly
defined in terms of reductions in future morbidity and mortality. Thus it is
normally assumed that it is the final health gains alone which bear utility. This
discounts the possibility that individuals may derive utility from the process of
health care and other outcomes as well as the end health states. Attributes such
as anxiety, reassurance, autonomy, regret and hope provide potential benefits or
disbenefits in addition to health gains. This paper explores the concept of
process utility in the specific context of preventive goods. Characteristics such
as information, awareness and autonomy are examined for two preventive goods--hip
protectors and mammographic screening. If individuals trade off process
attributes for final health outcomes, then to ignore process utility may lead to
a sub-optimal allocation of resources.
PMID- 10181502
TI - From selfish individualism to citizenship: avoiding health economics' reputed
'dead end'.
AB - Recent interpretations of citizenship are firmly rooted in the value of social
membership and social participation. Citizens are described as having a moral
right to draw upon the support of the community, but at the same time have a
responsibility to contribute to the provision of social services such as health
care. In contrast, contemporary health economics has been criticised for taking a
narrow and individualistic view of human behaviour. This paper examines the
extent to which economic theory and practice have been developed to accommodate a
more 'civic' view, namely, the notions of mutual concern for community members,
social participation and social rights. It is argued that because the provision
of health care is often linked to feelings of compassion and social
responsibility and not just to individual well-being, this sort of insight may
enrich economic analysis and, in turn, provide a way around health economics'
reputed 'dead end'.
PMID- 10181503
TI - From compliance to concordance: a challenge for contraceptive prescribers.
AB - In 1997 the Royal Pharmaceutical Society of Great Britain published a report
entitled From Compliance to Concordance: Achieving Shared Goals in Medicine
Taking. This article applies this new model--of doctors and patients working
together towards a shared goal--to the prescribing of hormonal forms of
contraception. It begins by critically evaluating the current dominant model of
contraceptive prescribing. It claims that this model tends to stereotype all
women, but particularly young, poor and black women, as unreliable and ill
informed contraceptors who need to be advised and even controlled by much more
knowledgeable and socially responsible family planning experts. The article then
suggests how a much more egalitarian model of contraceptive prescribing might be
put into practice, whilst acknowledging the existence of many serious obstacles
to such a radical shift within family planning services. In conclusion, the
article suggests that until contraceptive prescribers begin to take women's
experiences of, and concerns about, hormonal contraceptives seriously they will
fail to develop a potentially much more effective and liberating model of family
planning.
PMID- 10181504
TI - Health warnings on tobacco products: absolving the profiteer, punishing the
victim. The ethics of Australian legislation.
AB - In recent years, health warnings on tobacco products have become compulsory
through legislation introduced by the Australian government. This approach shows
a lack of concern for tobacco consumers while allowing government to abdicate
responsibility without jeopardising profit. The decision to warn people of
inevitable addiction and disease (while protecting those who profit from such
sales) fails to recognise previous research into adolescent attraction to
deviance and the role of suggestion in cure and illness. The Australian
government makes millions of dollars each year by taxing tobacco products--as
long as these profits continue to be directed almost exclusively into
consolidated revenue, smokers will remain victims of a system unconcerned with
exploitation.
PMID- 10181505
TI - Japan's egalitarian health care system: a brief historical analysis.
AB - Japan is one of several East Asian countries that share an ethical system of
mutual support. A review of Japan's health care system reveals a strong
egalitarian ethos often considered unique by outside observers.
PMID- 10181506
TI - Towards a global theory of health systems: Milton Roemer's National Health
Systems of the World.
PMID- 10181507
TI - The ethics of narrative ethics: some teaching reflections.
AB - Narrative is reemerging as a teaching tool. Narrative ethics is being seen as a
rich endeavour both for clinical practice and academic teaching and research.
Narrative helps put ethics into context. However, the use of narrative
increasingly raises issues in teaching and research: for instance, how do we do
justice to the people and narratives we utilise, and what does our practice
reveal about our ethics? In this article examples are drawn from clinical
practice, teaching and case notes to draw out some lessons to help further
critical understanding.
PMID- 10181508
TI - Political refutation of a scientific theory: the case of polio vaccines and the
origin of AIDS.
PMID- 10181509
TI - Mapping mental health: speculation beyond the microscope.
PMID- 10181510
TI - Beyond health outcomes: the benefits of health care.
AB - Most of the debate surrounding standards in medical care, issues of medical audit
and what constitutes benefit from health care assumes that what is obtained from
health care is health and only that. This is an assumption which most health
economists at least implicitly appear to endorse. This paper questions that
assumption. There are various outcomes beyond health and there are various
processes involved in health care about which patients are not indifferent. This
paper calls for a fuller investigation as to what it is that patients want from
their health services and the adoption of a more pluralistic conception of health
care benefits. It is further argued that the objectives of health care systems
are those in which citizens qua citizens also have interests and which may be
different from those of patients. It is yet less likely that citizens' interests
in health care will be restricted to health.
PMID- 10181511
TI - HHS management and budget office; statement of organization, function, and
delegations of authority.
PMID- 10181512
TI - Minor corrections, clarifying changes, and a minor policy change--NRC. Final
rule.
AB - The Nuclear Regulatory Commission is amending its regulations to make minor
corrections and clarifying changes to the NRC's 10 CFR Part 20, "Standards for
Protection Against Radiation." The final rule is also intended to conform other
regulations with the Commission's 1991 revised radiation protection requirements.
In addition, the final rule includes a minor policy change that raises the
monitoring criteria for minors from 0.05 rem (0.5 mSv) to 0.1 rem (1 mSv) in a
year and for declared pregnant women from 0.05 rem (0.5 mSv) to 0.1 rem (1 mSv)
during their pregnancies. The 0.1 rem (1 mSv) in a year deep dose equivalent
monitoring criterion is consistent with the public dose limit and represents a
quantity more consistent with the measurement sensitivity of individual personnel
dosimetry. Licensees are still required to ensure that the occupational dose
limit of 0.5 rem (5 mSv) in a year is not exceeded for minors, that the dose
limit of 0.5 rem (5 mSv) to an embryo/fetus due to occupational exposure of a
declared pregnant woman is not exceeded during the course of the pregnancy, and
that sufficient effort is made to ensure that substantial variations above a
uniform monthly exposure rate for a declared pregnant woman are avoided. These
changes to the threshold for monitoring exposures to radiation and radioactive
material to demonstrate compliance with the limits do not change the occupational
dose limits for minors or declared pregnant workers.
PMID- 10181513
TI - Payment for non-VA physician services associated with either outpatient or
inpatient care provided at non-VA facilities--VA. Final rule.
AB - This document amends Department of Veterans Affairs (VA) medical regulations
concerning payment for non-VA physician services that are associated with either
outpatient or inpatient care provided to eligible VA beneficiaries at non-VA
facilities. Generally, when a service-specific reimbursement amount has been
calculated under Medicare's Participating Physician Fee Schedule, VA would pay
the lesser of the actual billed change or the calculated amount. Also, when an
amount has not been calculated or when the services constitute anesthesia
services, VA would pay the amount calculated under a 75th percentile formula or,
in certain limited circumstances, VA would pay the usual and customary rate.
Adoption of this final rule is intended to establish reimbursement consistency
among federal health benefits programs to ensure that amounts paid to physicians
better represent the relative resource inputs used to furnish a service, and to
achieve program cost reductions. Further, consistent with statutory requirements,
the regulations continue to specify that VA payment constitutes payment in full.
PMID- 10181514
TI - Federal universal service support mechanisms--FCC. Proposed rule; request for
comments.
AB - In this document, the Commission seeks comment on the Report and Proposed Plan of
Reorganization (Plan) filed on July 1, 1998 by the Universal Service
Administrative Company (USAC), the Schools and Libraries Corporation (SLC), and
the Rural Health Care Corporation (RHCC). The Plan proposes a revised
adminstrative structure of the federal universal service support mechanisms. RHCC
filed a Separate Statement of the Rural Health Care Corporation and Request for
Three Changes in the Plan, dissenting from certain provisions of the proposed
Plan. In this document, the Commission also seeks comment on other issues
regarding the administration of the federal universal service support mechanisms,
including processes for Commission review of actions by USAC, SLC, and RHCC.
PMID- 10181515
TI - Medical use of byproduct material; public meetings--NRC. Notice of public
meetings.
AB - The Nuclear Regulatory Commission has developed a proposed rulemaking for a
comprehensive revision of its regulations governing the medical use of byproduct
material in 10 CFR Part 35, "Medical Use of Byproduct Material," and a proposed
revision of its 1979 Medical Use Policy Statement (MPS). Throughout the
development of the proposed rule and MPS, the Commission solicited input from the
various interests that may be affected by these proposed revisions. The
Commission now plans to solicit comments on the proposed rule and MPS through two
mechanisms--publishing the documents in the Federal Register for public comment
(scheduled for August 1998); and convening three facilitated public meetings,
during the public comment period, to discuss the Commission's proposed resolution
of the major issues. The public meetings will be held in San Francisco,
California, on August 19-20, 1998; in Kansas City, Missouri, on September 16-17,
1998; and in Rockville, Maryland, on October 21-22, 1998. All meetings will be
open to the public. Francis X. Cameron, Special Counsel for Public Liaison, in
the Commission's Office of the General Counsel, will be the convener and
facilitator for the meetings.
PMID- 10181516
TI - Medical devices; preemption of state product liability claims--FDA. Withdrawal of
proposed rule.
AB - The Food and Drug Administration (FDA) is announcing that it is withdrawing a
proposed rule that published in the Federal Register of December 12, 1997 (62 FR
65384), relating to medical device preemption of State product liability claims.
FDA is making this withdrawal because of concerns that have been raised regarding
the interplay between the FDA Modernization Act of 1997 (FDAMA) and the proposed
rule.
PMID- 10181517
TI - Orthopedic devices: classification and reclassification of pedicle screw spinal
systems--FDA. Final rule.
AB - The Food and Drug Administration (FDA) is classifying certain previously
unclassified preamendments pedicle screw spinal systems into class II (special
controls) and reclassifying certain postamendments pedicle screw spinal systems
from class III (premarket approval) to class II. FDA is taking this action
because it believes that special controls would provide reasonable assurance of
safety and effectiveness. This action is being taken under the Federal Food,
Drug, and Cosmetic Act (the act), as amended by the Medical Device Amendments of
1976 (the 1976 amendments), the Safe Medical Devices Act of 1990 (the SMDA), and
the Food and Drug Administration Modernization Act of 1997 (FDAMA).
PMID- 10181518
TI - Public information; communications with state and foreign government officials-
FDA. Proposed rule.
AB - The Food and Drug Administration (FDA) is proposing to amend its regulations
governing communications with State and foreign government officials. The
proposed rule would permit FDA to disclose confidential commercial information to
international organizations having responsibility to facilitate global or
regional harmonization of standards and requirements. These disclosures would, in
almost all instances, occur only with the consent of the person providing the
confidential commercial information to FDA. The proposed rule would also
streamline the process for FDA officials to disclose certain nonpublic,
predecisional documents (such as draft rules and guidance documents) to State and
foreign government officials. The proposal does not alter current procedures for
sharing documents that contain confidential commercial information. These changes
are intended to facilitate information exchanges with State and foreign
governments and certain international organizations.
PMID- 10181519
TI - Medical devices; neurological devices; classification of cranial orthosis--FDA.
Final rule.
AB - The Food and Drug Administration (FDA) is classifying the cranial orthosis into
class II (special controls). The special controls that will apply to the cranial
orthosis are restriction to prescription use, biocompatibility testing, and
certain labeling requirements. The agency is taking this action in response to a
petition submitted under the Federal, Food, Drug, and Cosmetic Act (the act) as
amended by the Medical Device Amendments of 1976, the Safe Medical Devices Act of
1990, and the Food and Drug Administration Modernization Act of 1997. The agency
is classifying cranial orthosis into class II (special controls) in order to
provide a reasonable assurance of safety and effectiveness of the device.
PMID- 10181520
TI - Medical devices; retention in class III and effective date of requirement for
premarket approval for three preamendments class III devices--FDA. Proposed rule;
opportunity to request a change in classification.
AB - The Food and Drug Administration (FDA) is proposing to retain in class III, three
preamendments class III medical devices, and is proposing to require the filing
of a premarket approval application (PMA) or a notice of completion of a product
development protocol (PDP) for these devices. FDA believes that the suction
antichoke device, the tongs antichoke device, and the implanted neuromuscular
stimulator device should remain in class III because insufficient information
exists to determine that special controls would provide reasonable assurance of
their safety and effectiveness, and/or these devices present a potential
unreasonable risk of illness or injury. The agency is summarizing its proposed
findings regarding the degree of risk of illness or injury designed to be
eliminated or reduced by requiring the devices to meet the statute's approval
requirements and the benefits to the public from the use of the devices. In
addition, FDA is announcing the opportunity for interested persons to request the
agency to change the classification of any of the devices based on new
information.
PMID- 10181521
TI - Medical devices; effective date of requirement for premarket approval for three
class III preamendments physical medicine devices--FDA. Proposed rule;
opportunity to request a change in classification.
AB - The Food and Drug Administration (FDA) is proposing to require the filing of a
premarket approval application (PMA) or a notice of completion of product
development protocol (PDP) for the following three high priority Group 3
preamendments class III devices: Microwave diathermy for uses other than
treatment of select medical conditions such as relief of pain, muscle spasms, and
joint contractures; ultrasonic diathermy for uses other than treatment of select
medical conditions such as relief of pain, muscle spasms, and joint contractures;
and ultrasound and muscle stimulator for uses other than treatment of select
medical conditions such as relief of pain, muscle spasms, and joint contractures.
The uses of these three devices do not include use for the treatment of
malignancies. The agency also is summarizing its proposed findings regarding the
degree of risk of illness or injury designed to be eliminated or reduced by
requiring the devices to meet the statute's approval requirements and the
benefits to the public from the use of the devices. In addition, FDA is
announcing the opportunity for interested persons to request that the agency
change the classification of any of these devices based on new information.
PMID- 10181522
TI - Regulations for in vivo radiopharmaceuticals used for diagnosis and monitoring;
extension of comment period--FDA. Proposed rule; extension of comment period.
AB - The Food and Drug Administration (FDA) is extending to October 15, 1998, the
comment period on a proposal rule that was published in the Federal Register of
May 22, 1998 (63 FR 28301). The document proposed to amend the drug and biologics
regulations by adding provisions that would clarify the evaluation and approval
of in vivo radiopharmaceuticals used in the diagnosis or monitoring of diseases.
The agency is taking this action to provide interested persons additional time to
submit comments to FDA on the proposed rule.
PMID- 10181523
TI - Breast center questions ... and mistakes.
PMID- 10181524
TI - Chemical substance abuse in radiology.
PMID- 10181525
TI - New NRC patient release guidelines: major quality of life & cost-containment
benefits.
PMID- 10181526
TI - R.S.V.P. Rectitude, not restriction, Sapient, not special, Veracity, not
victorian, Percipient, not perfect.
PMID- 10181527
TI - Equipment upgrades: the operation.
PMID- 10181528
TI - The impact of business cycles on imaging services and technology.
PMID- 10181529
TI - HMOs' 1997 losses may continue to affect providers in 1999.
PMID- 10181530
TI - What went wrong with HMOs in 1997?
PMID- 10181531
TI - Educate physicians to ease transition into 21st century.
PMID- 10181532
TI - IDS succeeds with Medicare risk contracts. CA system has 14,000 covered Medicare
lives.
PMID- 10181533
TI - Hospitalists are a sensible strategy for managing inpatient costs.
PMID- 10181534
TI - Mystery shopping provides valuable info for practices.
PMID- 10181535
TI - Clinical software eases switch to paperless office.
PMID- 10181536
TI - Stats & facts. The evolving employer coalition.
PMID- 10181537
TI - Are states' cost-cutting measures forcing HMOs from Medicaid?
PMID- 10181538
TI - Pharmacy technicians in managed care.
PMID- 10181539
TI - How to extend the role of the pharmacy technician.
PMID- 10181540
TI - Chronic low back pain: new perspectives and treatment guidelines for primary
care: Part II.
AB - Low back pain is a leading cause of work-related disability and has important
socioeconomic consequences. Although there is little evidence to determine the
optimal treatment of chronic low back pain, treatment goals can be established.
Primary care providers should focus simultaneously on pain management,
improvement of activity and functional level, and fostering a greater
understanding of chronic low back pain. This two-part article summarizes
consensus guidelines developed by practitioners with expertise in pain
management, family medicine, internal medicine, physical therapy, rheumatology,
and managed care and provides direction for primary care providers on a
multidisciplinary approach to the patient with chronic low back pain. This part
examines pharmacologic methods.
PMID- 10181541
TI - Physician's unions: handle with care.
AB - In an attempt to battle the growing number and expanding power of MCOs,
physicians are attempting to form or become a part of unions. By banding
together, doctors believe that they can fight the MCO's ever-tightening grip on
their practices and gain bargaining power that has been lost.
PMID- 10181543
TI - Stats & facts. Who are the uninsured?
PMID- 10181542
TI - An economic model for a novel viral influenza diagnostic.
AB - The authors present a model that tests the economic value of a new diagnostic
test that can identify type A and B influenza. Compared with traditional
treatment without trying to objectively differentiate viral from bacterial
infection, substantial cost savings may be achieved if diagnostic testing is
appropriately utilized in a comprehensive influenza management program.
PMID- 10181544
TI - Little ado about Congress.
PMID- 10181545
TI - A conversation with Daniel Dallabrida.
AB - Often, health plans find themselves at odds with consumer and patient advocacy
groups. Advocacy groups are usually the first to complain to the media and to
legislators when managed care companies cut back benefits that affect their
constituents. Yet, managed health care plans do little to work proactively with
advocacy groups to the benefit of both. Daniel Dallabrida is president of
Dallabrida & Associates in San Francisco, an organization that specializes in
creating this interface.
PMID- 10181546
TI - Disease state management and the Internet.
PMID- 10181547
TI - Managed care research participation and interests.
AB - Recent concerns about the future of American health care research have focused in
part on the growth of MCOs, which many believe are uninterested in research
participation. Managed care may hinder research by limiting patient access to
academic medical centers, and also by heightening competitiveness, which may
force these centers to reduce research funding. There may be, however, some
incentives for MCOs to participate in research, including the ability to pursue
unique research interests as well as attract potential members.
PMID- 10181548
TI - New payments and incentives in contact capitation: an orthopedics case study.
AB - The purpose of this article is to present a model for equitable distribution of
orthopedic contact capitation payments. This model accounts for services covered,
patient severity of illness, patient age, and condition prevalence.
PMID- 10181549
TI - A managed care consumer bill of rights.
PMID- 10181550
TI - Glaucoma.
AB - The routine, easiest-to-treat adult patients with glaucoma utilize 1.80 office
visits, 3.34 prescriptions, and 2.02 medical/surgical procedures during the
course of a year. Based on data from the PTE-Registry database, this patient
group did not receive any hospital admissions or professional inpatient services.
Eye surgery was performed at an average rate of 0.08 times per PTE. About 53.5%
of all PTEs were treated without the use of prescription drugs. When a drug was
prescribed, beta blockers were used most often. In fact, 74.1% of all PTEs
treated with a single drug group used a beta blocker.
PMID- 10181551
TI - Stats & facts. The increasing dominance of the pharmacy benefits manager.
PMID- 10181552
TI - Pharmaceutical care growing pains.
PMID- 10181553
TI - The genetics of breast cancer: can we use today's information?
PMID- 10181554
TI - Evidence-based drug formularies: hyperbole or reality?
PMID- 10181555
TI - Reducing malpractice risk and increasing quality in managed care.
AB - The Early Diagnosis Project was established in an effort to improve quality and
reduce malpractice risk in managed care practice environments. The first project,
which addressed breast cancer, utilized practice guidelines, patient handouts,
and follow-up forms in an integrated attempt to improve the quality of care and
reduce litigation involving "failure-to-diagnose" claims.
PMID- 10181556
TI - Information systems for the management services organization.
AB - The growth of the management of services organization has been accompanied by the
need for better information technology systems to track both patient and
physician utilization. The author describes some possible benefits of customizing
an information system to meet the needs of these specialized organizations.
PMID- 10181557
TI - Stats & facts. Information technology executive opinions on computerized patient
records.
PMID- 10181558
TI - Hemorrhoids.
AB - The patients with routine, easiest-to-treat hemorrhoids average 1.25 office
visits, 0.80 prescriptions, and 1.38 medical/surgical procedures during the
course of a year. About 63.9% of all PTEs were treated without the use of
prescription drugs. This patient group did not receive any hospital admissions or
professional inpatient services. Hemorrhoid surgery was performed at an average
rate of 1.37 times per PTE on an out-patient basis. Seventy-two percent of the
overall medical charges for hemorrhoid treatment are direct surgical charges. Of
the PTEs treated with a single drug group, only 1.5% are treated with a
prescription laxative. However, the use of OTC stool softeners and laxatives were
not measured in this analysis. Thus, an exact measurement of cost savings
associated with appropriate use of softeners/laxatives for the prevention of
recurrent hemorrhoids could not be determined. Considering the potential cost
savings of using laxatives for prevention of hemorrhoids, further investigation
of the prescribing patterns of this specialty may prove useful.
PMID- 10181559
TI - Critical pathways: a program description in a national MCO.
PMID- 10181560
TI - Sharing strategic information.
PMID- 10181561
TI - Medication processing: closing the provider-pharmacy gap.
AB - The provision of medications to patients is not a departmental task managed by
the pharmacy. Rather, it is an enterprise-wide task with management shared by
physicians, pharmacists, and nurses. Only automation approaches that integrate
all three axes in real time will be able to effectively support the desired goal:
the optimal provision of the proper medication to the proper patient at the
proper time.
PMID- 10181562
TI - Enrollee retention and disease state management.
PMID- 10181563
TI - Retention of patients with a diagnosis of diabetes in selected managed care
plans.
AB - This study was designed to determine the extent of retention of patients in staff
model HMOs. Study groups with Type II diabetes were compared with a control group
without diabetes. Each study group (three groups of approximately 400 patients,
drawn from three MCOs) was enrolled in a staff-model HMO in 1990. Patients were
then followed for five consecutive years through 1995. The age- and gender
matched control groups (approximately 400 patients randomly selected from each of
the three MCOs) were identified from managed care plan enrollees without a
diagnosis of diabetes. It was found that the retention rates of patients with
diabetes are higher than those without diabetes in two plans. For the third plan,
the retention rates among patients with diabetes were the same as the control
group's. The first year of enrollment was found to be the most important
predictor of patient retention. The findings of this study strongly suggest plans
seek methods to optimize treatments and delay the natural history, morbidity, and
exacerbations associated with diabetes, since there is a higher probability that
these patients will be members in the future.
PMID- 10181564
TI - Doctor choice equals happiness in managed care.
PMID- 10181565
TI - Keeping patients with arthritis out of the hospital.
AB - The use of nonsteroidal anti-inflammatory drugs in the treatment of
osteoarthritis and rheumatoid arthritis is frequently associated with
gastrointestinal complications, particularly gastric bleeding. The author
outlines a strategy for avoiding these complications, thereby decreasing the risk
for hospitalization and/or death.
PMID- 10181566
TI - Asking the physician to rate health plans.
PMID- 10181567
TI - Stats & facts. The rapidly growing market of erectile dysfunction.
PMID- 10181568
TI - Urinary tract infections.
AB - Women between the ages of 18 years and 64 years with the easiest-to-treat UTIs
average 1.07 office visits, 2.36 prescriptions, and 2.34 laboratory and pathology
services per PTE. Laboratory services were performed an average of 2.27 times per
PTE on an outpatient basis. This patient group did not receive a significant
amount of hospital admissions or professional inpatient services. Approximately
71% of all PTEs were treated with pharmaceutical therapy. Of the overall charges
for UTIs, 31% were for prescription drug therapy. Of those patients treated with
a single drug group, almost 33% were treated with trimethoprim/sulfamethoxazole
and 13.2% were treated with a fluoroquinolone. Considering the potential cost
savings of encouraging adherence to clinical prescribing guidelines, further
investigation of physician prescribing patterns for uncomplicated UTIs may prove
valuable to health plans.
PMID- 10181569
TI - Will physicians lead in the second generation of Medicare managed care?
AB - The one common principle in both managed care today and in the development of new
Medicare strategies is increasing physician power from the standpoints of both
clinical decision making and governance. In this article, the author explores a
few initiatives that seek to hasten the emergence of this "second generation" of
Medicare managed care.
PMID- 10181570
TI - Academic health centers: privileged market players?
PMID- 10181571
TI - Reimbursement for cognitive pharmacy services.
PMID- 10181573
TI - The role of comorbidities in disease state management.
PMID- 10181572
TI - Principal findings from the Washington State cognitive services demonstration
project.
AB - In addition to dispensing, pharmacists are ideally positioned to provide
cognitive services that are targeted at optimizing drug therapy through
identification and resolution of drug therapy problems. The Washington Cognitive
Activities and Reimbursement Effectiveness project sought to determine: (1) if
pharmacists would respond to a financial incentive by performing more cognitive
services, and (2) the effect on drug cost of cognitive services they performed.
PMID- 10181574
TI - Federal tax rules for joint ventures between charities and noncharities.
AB - This article reviews the general principles that govern joint ventures between
charitable and for-profit entities, examines the new IRS guidelines, and
discusses the application of both principles and guidelines to MCOs.
PMID- 10181575
TI - OIG issues guidance to hospitals seeking to reduce fraud and abuse risks.
PMID- 10181576
TI - The organization and economics of prostate seed implantation programs.
PMID- 10181577
TI - Oncology in the era of managed care.
AB - The field of oncology, both with regards to clinical care as well as research, is
rapidly changing in response to the current changes in our health care delivery
system. Cancer is the second leading cause of death in the United States,
exceeded only by heart disease. Cancer care, including screening, diagnosis,
treatment, and supportive care, consumes approximately 15% of all health care
costs in the United States. The National Cancer Institute estimates the overall
costs for cancer at $104 billion per year. Despite the increasing incidence of
cancer, federal funding for cancer research has actually declined. Managed care's
emphasis on cost reduction is threatening all aspects of the care of patients
with cancer. Along these same lines, clinical research support has been
dramatically affected by managed care. The major critical issues in the future
will be guaranteed access of patients to high-quality cancer care, access to
qualified clinical trials, promotion of cancer prevention programs, and support
of professional education in oncology. The American Cancer Society estimates that
in 1997, 1,382,400 new cases of cancer are expected to be diagnosed in the United
States. This year alone, 560,000 Americans are expected to die of cancer. Cancer
is the second leading cause of death in the United States, exceeded only by heart
disease. One of every four deaths in the United States is due to cancer. The
field of oncology, both with regards to clinical care as well as research, is
rapidly changing in response to the current changes in our health care delivery
system. This paper will address how these changes are having a major impact on
the practice of cancer care in the United States.
PMID- 10181578
TI - Understanding financial responsibility in managed care!
PMID- 10181579
TI - Perspectives. Medicare's silent partners: reform of contractor system slowed as
Y2K tangle spotlights unheralded intermediaries.
PMID- 10181580
TI - Marketplace. Conflict over payments will drag on; plans and providers face new
pressures.
PMID- 10181581
TI - Perspectives. POS proposals promise choice, may be cheap; but loopholes abound
and "nobody is paying any attention".
PMID- 10181582
TI - Perspectives. Limited-service rural hospital program going national after years
of incubation, but seed-money appropriation is stalled.
PMID- 10181583
TI - Meeting patient expectations: survey data shows room for better communication.
PMID- 10181584
TI - 'For profit,' 'nonprofit' may no longer be meaningful.
PMID- 10181585
TI - The promise--and peril--of integrated cost systems.
AB - Recent advances in managerial accounting have helped executives get the
information they need to make good strategic decisions. But today's enterprise
resource planning systems promise even greater benefits--the chance to integrate
activity-based costing, operational-control, and financial reporting systems. But
managers need to approach integration very thoughtfully, or they could end up
with a system that drives decision making in the wrong direction. Operational
control and ABC systems have fundamentally different purposes. Their requirements
for accuracy, timeliness, and aggregation are so different that no single, fully
integrated approach can be adequate for both purposes. If an integrated system
used real-time cost data instead of standard rates in its ABC subsystem, for
example, the result would be dangerously distorted messages about individual
product profitability--and that's precisely the problem ABC systems were
originally designed to address. Proper linkage and feedback between the two
systems is possible, however. Through activity-based budgeting, the ABC system is
linked directly to operations control: managers can determine the supply and
practical capacity of resources in forthcoming periods. Linking operational
control to ABC is also possible. The activity-based portion of an operational
control system collects information that, while it mustn't be fed directly into
the activity-based strategic cost system, can be extremely useful once it's been
properly analyzed. Finally, ABC and operational control can be linked to
financial reporting to generate cost of goods sold and inventory valuations--but
again, with precautions.
PMID- 10181586
TI - Putting the enterprise into the enterprise system.
AB - Enterprise systems present a new model of corporate computing. They allow
companies to replace their existing information systems, which are often
incompatible with one another, with a single, integrated system. By streamlining
data flows throughout an organization, these commercial software packages,
offered by vendors like SAP, promise dramatic gains in a company's efficiency and
bottom line. It's no wonder that businesses are rushing to jump on the ES
bandwagon. But while these systems offer tremendous rewards, the risks they carry
are equally great. Not only are the systems expensive and difficult to implement,
they can also tie the hands of managers. Unlike computer systems of the past,
which were typically developed in-house with a company's specific requirements in
mind, enterprise systems are off-the-shelf solutions. They impose their own logic
on a company's strategy, culture, and organization, often forcing companies to
change the way they do business. Managers would do well to heed the horror
stories of failed implementations. FoxMeyer Drug, for example, claims that its
system helped drive it into bankruptcy. Drawing on examples of both successful
and unsuccessful ES projects, the author discusses the pros and cons of
implementing an enterprise system, showing how a system can produce unintended
and highly disruptive consequences. Because of an ES's profound business
implications, he cautions against shifting responsibility for its adoption to
technologists. Only a general manager will be able to mediate between the
imperatives of the system and the imperatives of the business.
PMID- 10181587
TI - How hardwired is human behavior?
AB - Time and time again managers have tried to eliminate hierarchies, politics, and
interorganizational rivalry--but to no avail. Why? Evolutionary psychologists
would say that they are working against nature--emotional and behavioral
"hardwiring" that is the legacy of our Stone Age ancestors. In this evolutionary
psychology primer for executives, Nigel Nicholson explores many of the Science's
central tenets. Of course, evolutionary psychology is still an emerging
discipline, and its strong connection with the theory of natural selection has
sparked significant controversy. But, as Nicholson suggests, evolutionary
psychology is now well established enough that its insights into human instinct
will prove illuminating to anyone seeking to understand why people act the way
they do in organizational settings. Take gossip. According to evolutionary
psychology, our Stone Age ancestors needed this skill to survive the socially
unpredictable conditions of the Savannah Plain. Thus, over time, the propensity
to gossip became part of our mental programming. Executives trying to eradicate
gossip at work might as well try to change their employees' musical tastes.
Better to put one's energy into making sure the "rumor mill" avoids dishonesty or
unkindness as much as possible. Evolutionary psychology also explores the
dynamics of the human group. Clans on the Savannah Plain, for example, appear to
have had no more than 150 members. The message for managers? People will likely
be most effective in small organizational units. As every executive knows, it
pays to be an insightful student of human nature. Evolutionary psychology adds
another important chapter to consider.
PMID- 10181589
TI - Welcome to the experience economy.
AB - First there was agriculture, then manufactured goods, and eventually services.
Each change represented a step up in economic value--a way for producers to
distinguish their products from increasingly undifferentiated competitive
offerings. Now, as services are in their turn becoming commoditized, companies
are looking for the next higher value in an economic offering. Leading-edge
companies are finding that it lies in staging experiences. To reach this higher
level of competition, companies will have to learn how to design, sell, and
deliver experiences that customers will readily pay for. An experience occurs
when a company uses services as the stage--and goods as props--for engaging
individuals in a way that creates a memorable event. And while experiences have
always been at the heart of the entertainment business, any company stages an
experience when it engages customers in a personal, memorable way. The lessons of
pioneering experience providers, including the Walt Disney Company, can help
companies learn how to compete in the experience economy. The authors offer five
design principles that drive the creation of memorable experiences. First, create
a consistent theme, one that resonates throughout the entire experience. Second,
layer the theme with positive cues--for example, easy-to-follow signs. Third,
eliminate negative cues, those visual or aural messages that distract or
contradict the theme. Fourth, offer memorabilia that commemorate the experience
for the user. Finally, engage all five senses--through sights, sounds, and so on-
to heighten the experience and thus make it more memorable.
PMID- 10181588
TI - Connectivity and control in the year 2000 and beyond.
AB - By now, most executives are familiar with the famous Year 2000 problem--and many
believe that their companies have the situation well in hand. After all, it seems
to be such a trivial problem--computer software that interprets "oo" to be the
year 1900 instead of the year 2000. And yet armies of computer professionals have
been working on it--updating code in payroll systems, distribution systems,
actuarial systems, sales-tracking systems, and the like. The problem is
pervasive. Not only is it in your systems, it's in your suppliers' systems, your
bankers' systems, and your customers' systems. It's embedded in chips that
control elevators, automated teller machines, process-control equipment, and
power grids. Already, a dried-food manufacturer destroyed millions of dollars of
perfectly good product when a computer counted inventory marked with an
expiration date of "oo" as nearly a hundred years old. And when managers of a
sewage-control plant turned the clock to January I, 2000 on a computer system
they thought had been fixed, raw sewage pumped directly into the harbor. It has
become apparent that there will not be enough time to find and fix all of the
problems by January I, 2000. And what good will it do if your computers work but
they're connected with systems that don't? That is one of the questions Harvard
Business School professor Richard Nolan asks in his introduction to HBR's
Perspectives on the Year 2000 issue. How will you prepare your organization to
respond when things start to go wrong? Fourteen commentators offer their ideas on
how senior managers should think about connectivity and control in the year 2000
and beyond.
PMID- 10181590
TI - CHA: uniting our individual strengths.
PMID- 10181591
TI - Celebrating the legacy of a mission.
AB - In 1995, Holy Family Hospital, in Prince Albert, Saskatchewan, Canada, began the
process of closing its doors. Holy Family Hospital, operated by the Sisters of
Charity of the Immaculate Conception, had been tending the sick for 87 years, and
was a large employer in the area. Its roots ran deep in the community. In
September 1997, Sr. McMullen spoke to hospital employees, provincial and civic
leaders, and community religious figures at a banquet marking the culmination of
the long and difficult process.
PMID- 10181592
TI - President's address. The faces of a community in ministry: passionate,
determined, responsible.
PMID- 10181593
TI - Mission-driven market strategies: lessons from the field. A study of six
successful Catholic systems finds mission and values clarity more relevant than
ever.
AB - Convinced that Catholic organizations might have special strengths for succeeding
in price-competitive markets, the Catholic Health Association, with the
assistance of a national membership advisory committee and The Lewin Group,
Fairfax, VA, studied six healthcare organizations that are successfully meeting
the challenges of difficult environments. Based on more than 100 interviews and
assessments of the environments in which these progressive mission-driven
organizations operate, the researchers identified strategies that can assist
other faith-based health organizations. The Lewin Group's Kevin J. Sexton, who
led the research team, explained that "the study examined how the organizations
embraced their mission and used their values in three areas: linkages with other
organizations, linkages with physicians, and strategies for balancing delivery
and insurance." CHA's executive vice president William J. Cox said the study
sites were selected to obtain a range of marketplace, sponsorship, and structural
experiences. "We wanted to learn how Catholic organizations responded to
environmental forces with strategies that were grounded in mission," Cox said.
CHA has published the study in a resource packet that describes the five major
findings, profiles the cases, and provides Best Practices Checklists--specific
pointers to guide organizations in their efforts. The following study excerpts
provide a brief overview of the findings and a sample of the Best Practices
Checklists. To obtain the complete resource, Mission-Driven Market Strategies:
Lessons from the Field, call the Catholic Health Association at 314-253-3458 (for
more information see the advertisement on p. 62).
PMID- 10181594
TI - New Catholic systems, new strategic questions. Planning must now effectively
integrate local efforts with the ministry as a whole.
PMID- 10181595
TI - Eight lessons on collaboration. The Daughters of Charity National Health System
experience.
PMID- 10181596
TI - Applying the Directives. The Ethical and Religious Directives concerning three
medical situations require some elucidation.
PMID- 10181597
TI - Covenant model of corporate compliance. "Corporate integrity" program meets
mission, not just legal, requirements.
AB - Catholic healthcare should establish comprehensive compliance strategies, beyond
following Medicare reimbursement laws, that reflect mission and ethics. A
covenant model of business ethics--rather than a self-interest emphasis on
contracts--can help organizations develop a creed to focus on obligations and
trust in their relationships. The corporate integrity program (CIP) of Mercy
Health System Oklahoma promotes its mission and interests, educates and motivates
its employees, provides assurance of systemwide commitment, and enforces CIP
policies and procedures. Mercy's creed, based on its mission statement and core
values, articulates responsibilities regarding patients and providers, business
partners, society and the environment, and internal relationships. The CIP is
carried out through an integrated network of committees, advocacy teams, and an
expanded institutional review board. Two documents set standards for how Mercy
conducts external affairs and clarify employee codes of conduct.
PMID- 10181599
TI - Putting patients first. Enhancing spiritual well-being.
PMID- 10181598
TI - "Spirit care" treats both soul and body. With new approach, system demonstrates
Catholic healthcare's extra dimension.
PMID- 10181601
TI - Catholic Health Association's 1998-99 strategic plan. Combining our strengths for
the common good.
PMID- 10181600
TI - Innovative rehabilitation techniques create success.
PMID- 10181602
TI - Advances and retreats in outpatient medical technology.
PMID- 10181603
TI - Identifying opportunities to improve the management of care: a population-based
diagnostic methodology.
AB - The growth of managed care and specifically capitation will dramatically change
the basis of competition for health care providers. In order for medical groups
to succeed in this new environment they must be able to accept the accountability
for both managing the care of populations and managing the delivery of individual
encounters of care. Being held accountable for the management of populations will
require at-risk medical groups to focus on developing three entirely new
strategic capabilities: the assessment of health risk, the management of access,
and the management of care. This article describes the analytic approach of
Deloitte & Touche Consulting Group's population-based diagnostic methodology,
which will enable an at-risk organization to identify opportunities for improving
the management of care for specific populations and diseases. The hypotheses
driving the need for these organizations to establish population-based care
management capabilities stem from the plethora of empirical evidence indicating
significant variation in costs, utilization, and outcomes in the practice of
medicine. Applying a systematic, planned approach to caring for patients who have
common, predictable health care needs will result in better outcomes and lower
costs for all.
PMID- 10181604
TI - Episodes of illness: a summary of the state of the art and future directions.
PMID- 10181605
TI - Redesigning ambulatory care business processes supporting clinical care delivery.
AB - The first step in redesigning the health care delivery process for ambulatory
care begins with the patient and the business processes that support the patient.
Patient-related business processes include patient access, service documentation,
billing, follow-up, collection, and payment. Access is the portal to the clinical
delivery and care management process. Service documentation, charge capture, and
payment and collection are supporting processes to care delivery. Realigned
provider networks now demand realigned patient business services to provide their
members/customers/patients with improved service delivery at less cost. Purchaser
mandates for cost containment, health maintenance, and enhanced quality of care
have created an environment where every aspect of the delivery system, especially
ambulatory care, is being judged. Business processes supporting the outpatient
are therefore being reexamined for better efficiency and customer satisfaction.
Many health care systems have made major investments in their ambulatory care
environment, but have pursued traditional supporting business practices--such as
multiple access points, lack of integrated patient appointment scheduling and
registration, and multiple patient bills. These are areas that are appropriate
for redesign efforts--all with the customer's needs and convenience in mind.
Similarly, setting unrealistic expectations, underestimating the effort required,
and ignoring the human elements of a patient-focused business service redesign
effort can sabotage the very sound reasons for executing such an endeavor.
Pitfalls can be avoided if a structured methodology, coupled with a change
management process, are employed. Deloitte & Touche Consulting Group has been
involved in several major efforts, all with ambulatory care settings to assist
with the redesign of their business practices to consider the patient as the
driver, instead of the institution providing the care.
PMID- 10181606
TI - Ambulatory care growth: implications for academic organizations.
AB - This article discusses the implications of the dramatic growth of outpatient
activity in academic health care organizations, and, more broadly, in all forms
of joint physician-hospital outpatient care. The authors describe several
economic, operational, and regulatory factors that influence the success of
ambulatory care expansion in the academic environment. A case study of the
Metropolitan New York Medicaid managed care environment illustrates the impact of
these factors and highlights the specific challenges confronting teaching
hospitals and physicians. The attributes of ambulatory care providers that have
successfully addressed these challenges are also discussed. Finally, the benefits
of the model ambulatory practice structure, employed at a number of teaching
institutions across the country, are explored.
PMID- 10181607
TI - Opportunities for optimizing resource utilization in ambulatory academic
practices.
AB - Growing emphasis on ambulatory service delivery in academic medical centers has
heightened interest in improving operational efficiencies, while providing an
optimal educational experience for medical students and residents. One
significant challenge in the academic environment is maximizing resource
utilization (both physical plant and personnel), through scheduling and
operational effectiveness. This article examines how academic ambulatory
practices can apply operational and scheduling process redesign methodologies to
improve throughput and productivity, while enhancing the educational experience
for students/residents.
PMID- 10181608
TI - Women's health services: restructuring for Medicaid managed care.
AB - New Jersey health care providers face the need to change dramatically the way
health care is delivered as it enters a new era of managed care. This year, more
than 24% of New Jersey's total population is enrolled in commercial managed care
plans (New Jersey Department of Insurance, 1996). In addition, the state's
Medicaid agency took steps to improve the delivery of health services to
recipients by initiating implementation activities to transition from the
traditional Medicaid program to a managed care model. Eighty-two percent of New
Jersey's Aid to Families with Dependent Children (AFDC) and related populations
have already been enrolled in managed care. The state plans to expand enrollment
in managed care to the remaining 400,000 Medicaid beneficiaries. Communities with
high Medicaid populations are challenged with the need to move through the
managed care evolution at an accelerated rate.
PMID- 10181609
TI - Emerging trends affecting ambulatory care: findings from an environmental
assessment.
AB - Deloitte & Touche LLP, in conjunction with VHA, Inc., conducts an annual
environmental assessment of trends affecting the health care industry. The annual
study assesses the impact of these trends on both providers and purchasers. This
article focuses on specific trends from our current study that suggest the need
for significant change in the way ambulatory care is delivered. The article
examines 10 key trends in overview, takes a closer look at four critical areas
with special impact on ambulatory care, and concludes with a discussion of how
the industry is responding.
PMID- 10181610
TI - Profiling the health service needs of populations using diagnosis-based
classification systems.
AB - Managed care presents the challenge to deliver health care services to
populations from a fixed pool of dollars and be accountable for doing so. From a
health plan and a community perspective, it is critical to have classification
systems that adequately describe the health service needs of the population. This
article describes the design and structure of the National Association of
Children's Hospitals and Related Institutions Classification of Congenital and
Chronic Health Conditions and illustrates its management applications from its
first testing on a full-service, paid claims database. Capabilities and
limitations of diagnosis-based classification systems and the International
Classification of Diseases, Ninth Edition, Clinical Modification diagnosis codes
that underpin such systems are discussed.
PMID- 10181611
TI - Strengthening partnerships between state programs for children with special
health care needs and managed care organizations.
AB - The roles and responsibilities of state Title V Programs for Children with
Special Health Care Needs (CSHCN) are changing with the rapid expansion of
managed care. The authors surveyed Title V CSHCN programs to learn about critical
issues and examples of collaboration with managed care organizations in the
following areas: (1) defining and identifying children with special health care
needs, (2) enrollment assistance and family participation, (3) pediatric provider
and service requirements, (4) education and training, (5) quality of care, and
(6) pediatric risk-adjusted capitation mechanisms. This article also includes
recommendations developed by the federal Maternal and Child Health Bureau's Work
Group on Managed Care.
PMID- 10181613
TI - The clinical development of an ambulatory classification system: version 2.0
Ambulatory Patient Groups.
AB - In 1995, the Health Care Financing Administration submitted a Report to Congress
recommending the Ambulatory Patient Groups (APGs), or an APG-like patient
classification system, be used as the basis of a Medicare outpatient prospective
payment system (PPS). Version 2.0 of APGs has been developed in anticipation of
its potential use in a Medicare outpatient PPS. The development process and final
structure of Version 2.0 of the APGs is described.
PMID- 10181612
TI - Evaluation of a prospective payment system for hospital-based outpatient care.
AB - The design of a prospective payment system (PPS) for outpatient care based on
ambulatory patient groups (APGs) requires numerous policy decisions to be made.
The policy issues include the method of computing payment weights, the extent of
ancillary packaging, the window of time for ancillary packaging, the extent of
multiple procedure discounting, and the outlier policy. Financial simulations of
an APG-based outpatient PPS were performed in order to evaluate the impact of
alternative policy decisions. Recommendations are made relative to each policy
issue.
PMID- 10181614
TI - Understanding and coping with the new HCFA physician incentives stop-loss
insurance rules.
AB - The imposition of physician incentive regulations by the Health Care Financing
Administration for Medicare risk and Medicaid managed care contracts has created
disclosure and stop-loss reinsurance issues for both physician groups and their
contracting health maintenance organizations. This article summarizes the key
points of the stop-loss requirements of the new rules, describes the current
types of stop-loss reinsurance purchased prior to the effective date of the
regulations, and the practical problems of conforming current physician group
contracting practices to these rules. The article also provides several suggested
steps that physician groups should take to manage the changes required.
PMID- 10181615
TI - Inauguration address to the University of Rochester School of Medicine and
Dentistry.
PMID- 10181616
TI - A primer on risk management for ambulatory surgery.
AB - This article shows that the trend for many types of surgery to move outside the
inpatient hospital setting to ambulatory settings has implications for risk
management in the areas of patient selection, patient education, physician
credentialing, communication and documentation, discharge planning, and patient
follow-up. This article identifies risk exposures in ambulatory surgery and
presents strategies for mitigating these risks.
PMID- 10181617
TI - A framework for selecting outcome measures for ambulatory care research.
AB - Selecting outcome measures must be considered in the context of the application
the researcher has in mind, that is, describing the health of a population,
predicting health status, or evaluating health outcomes. Most important, the
outcome measure selected must be conceptually defensible--it needs to make sense.
A general framework for selecting measures is discussed in the context of five
critical characteristics: (1) sensibility, (2) reliability, (3) validity, (4)
responsiveness, and (5) burden. A commonsense approach to outcome measurement
selection weighs the relative importance of each of these characteristics with
the framework and application clearly in mind.
PMID- 10181618
TI - Conducting clinical and health economic outcome studies in an ambulatory setting.
AB - Increasingly, health care practitioners are addressing economic (health care
resource utilization) and nonclinical (patient satisfaction and quality of life)
outcomes along with traditional clinical outcomes (morbidities, mortalities, cure
rates, etc.) in assessing the impact and quality of care provided to their
patients. These additional outcomes also are collected to assist health care
providers to meet accreditation standards and to aid in the selection of
alternative health care interventions in an environment of limited resources.
This article reviews the advantages and disadvantages of assessing both clinical
and nonclinical outcomes. A review of key questions that health economic and
outcome studies should answer is provided. In addition, relevant resource
utilization and outcome measures are identified based on a variety of
provider/payer perspectives. Finally, a framework to develop a strategic
operating plan for measuring and valuing outcome measures in an ambulatory
setting is presented.
PMID- 10181619
TI - Database system to identify biological risk in managed care organizations:
implications for clinical care.
AB - The investigators constructed an index measure of cardiovascular risk and scored
1.991 adults as having high, average, or low cardiovascular risk. High
cardiovascular risk was positively associated with hospital admissions (odds
ratio [OR] = 3.9, p < 0.0001), total hospital days (OR = 4.0, p < 0.001), primary
care clinic visits (OR = 7.3, p < 0.0001), and subspecialty clinic visits (OR =
2.3, p = 0.0003), compared to low cardiovascular risk, after controlling in
multivariate analyses for gender and age. The index can provide estimates of
utilization, costs, and potential preventability of adverse cardiovascular
events, can be used to identify groups of patients in need of various systematic
interventions, and can provide population-based ways to evaluate the results of
interventions.
PMID- 10181620
TI - Systems approach to population health improvement.
AB - Managed care organizations (MCOs) are uniquely well positioned to implement
population health initiatives. In an MCO setting, populations may be clearly
defined. Health care may be provided via integrated clinical care delivery
systems. Centralized services such as information systems, community relations,
health promotion and disease prevention support, and marketing campaigns may aid
in the achievement of population health improvement objectives. However, in order
to sustain population health improvement efforts long-term, continued support and
allocation of critical resources are needed. For this to occur, efforts need to
be integrated with the personal, social, economic, regulatory, and business
objectives of all key stakeholders involved in this process. Furthermore, the
process needs to continuously generate deliverables in order to allow for ongoing
feedback, evaluation, accountability, relationship building and maintaining, and
continuous quality improvement to occur. Hence, specific strategies may be
considered from a systems perspective. The present article describes a systems
approach in which a population health cycle generates health improvement outcomes
that are used to provide the rationale for continued allocation of resources.
PMID- 10181621
TI - Primary care, process improvement, and turmoil.
AB - The current health care environment in the United States is in turmoil,
especially in regions that are further ahead in the transition from free-for
service to managed care. This article examines turmoil within primary care during
a health-maintenance-organization-sponsored and federally funded randomized trial
of using continuous quality improvement for adult clinical preventive services.
The external and internal changes in structure and leadership occurring in
primary care clinics are profound and prevalent. The sponsors of the project have
responded to the turmoil by encouraging greater leadership involvement within the
clinic and by supporting more skill building for change management.
PMID- 10181622
TI - Population-based research data as a means to address health outcomes.
AB - Health care restructuring efforts have been influenced by changes in public
policy, payment mechanisms, and societal values. In today's environment, leading
issues focus on quality and cost-effective care. Health care systems are moving
from a concentration on structures and processes of care to an expanded view that
encompasses the exploration, documentation, and improvement of patient outcomes.
This article presents an overview of the domains of health outcomes, widely used
surveys in the measurement of outcomes, methodological issues related to
interpreting outcome measures, and trends for clinical practice and future
research.
PMID- 10181624
TI - Comparison of three visit-specific patient satisfaction instruments: reliability
and validity measures and the effect of four methods of data collection on
dimensions of patient satisfaction.
AB - The purposes of this study were to evaluate the reliability and validity of three
short-form patient satisfaction instruments and to examine the effects of data
collection methods on patient satisfaction ratings. With a framework to assess
quality of care from the patient's perspective, acceptability, accessibility,
patient satisfaction rating, provider recommendation, and patient demographic
data were collected using three patient surveys: the Health Outcomes Institute
questionnaire (HOI); the Nalle Clinic survey (Nalle); and a commercially marketed
survey (COM). The four methods of data collection were (1) receptionist
distributed at check-in, (2) student-distributed at check-out, (3) mail, and (4)
phone. Data were collected on a systematically selected sample of 1,840 patients
who were appointed in two family practice departments of the Nalle Clinic in
Charlotte, North Carolina. From the 925 completed surveys, the results indicated
that the HOI instrument scored higher on the reliability and validity measures in
this patient sample than the Nalle or COM surveys. Analysis of variance was then
conducted on the HOI scores across the four methods of data collection. The
conclusion was that the method of data collection did not significantly influence
any of the patient satisfaction indicators in the family practice sample.
PMID- 10181623
TI - Assessing the impact of clinical guidelines: research lessons learned.
AB - Clinical guidelines are proliferating. Here, a theoretical and practical
perspective is presented on how to evaluate the effectiveness of guidelines and
lessons learned from impact studies conducted. A nosology of guidelines is
presented, along with the rationale for evaluating key dimensions, including
degree of implementation, impact on process, outcomes, and cost of care, as well
as provider and patient satisfaction. Key methodologic problems in evaluation and
some possible ways to address them are addressed. Rapid and practical evaluation
of clinical guidelines is a critical step that can both confirm their usefulness
and direct their revision and improvement.
PMID- 10181625
TI - A performance evaluation system for primary care providers in a community health
services program.
AB - A performance evaluation system (PES) serves to motivate employees to provide
desired behaviors that achieve organizational objectives. In 1989, Denver Health
and Hospital (DHH), a publicly funded, integrated delivery system with a large
primary care program, instituted a new PES. This report summarizes performance
evaluation results for DHH's community health center program. The evaluation
focused on the performance of primary care physicians, midlevel practitioners
(i.e., physicians assistants, nurse practitioners, and dentists), over a 4-year
study period (1990 to 1993). Category-specific performance ratings were based on
a 5-point ordinal scale: unacceptable, expectations not met, meets expectations,
exceeds expectations, and outstanding. Performance ratings were analyzed as
variables that were dependent on several practice characteristics. Results
demonstrated a relationship between performance ratings and specific practice
characteristics. Based on the results, limitations of the new PES and
implications for designing more effective evaluation systems are discussed.
PMID- 10181626
TI - Lied to for a living.
PMID- 10181627
TI - Hot products. Some of the most talked about products from the 1998 EMS Today
Conference in Baltimore.
PMID- 10181628
TI - Sterling Sarasota.
PMID- 10181630
TI - So who is your customer?
PMID- 10181629
TI - Risking everything. EMTs, universal precautions, and AIDS.
PMID- 10181631
TI - Management by magic.
PMID- 10181632
TI - The quality and cost of medical care. The potential for information technology to
meet the challenge.
AB - The rising cost of health care has precipitated a variety of cost containment
initiatives. With the accelerated transition to managed care, the question of
quality has emerged. The feeling of many is that cost reduction alone can have
only one effect, a reduction in quality. In response, many have focused on the
need to reassess and reengineer the processes involved in the delivery of care
and to integrate these processes to ensure better management of the patient
through the monitoring of the continuum of care. In this paper, we describe the
potential for the application of an information technology, known as workflow
management technology, in the design and control of health care delivery
processes.
PMID- 10181633
TI - Community service: starting a not-for-profit foundation.
AB - The values statement of Medford Clinic is "dedication to excellence in health
care, serving our communities with integrity, respect and compassion."
Contributing directly to the community is a natural extension of our basic values
as health care providers and professionals. Medford Clinic Foundation was created
in 1996 to communicate our values and to express our gratitude by contributing to
our community directly and personally. Our foundation was formed to generate
funds to invest in the future of our community. We chose youth as the theme for
our contributions. Generally, we make small grants to individual children rather
then supporting on-going programs or non-profit agencies. We target the special
one-time needs of unique children in our community.
PMID- 10181635
TI - Stress, burnout and physician productivity.
AB - Stress and burnout are increasingly a part of physician's lives. Lower
reimbursements and heavier patient loads can contribute to a sense of despair.
Such burnout can have consequences for a group practice's bottom line. Stressed
physicians are less motivated and more likely to quit, creating the need to hire
and train new physicians. However, total practice management can help control the
problem.
PMID- 10181634
TI - How to build a specialty MSO.
AB - The specialty-based management services organization (MSO), with its focus on
management support, contracting, information systems and related benefits, is
intended to help preserve specialist physician access to patients. It does this
by enabling the MSO's physicians to clearly differentiate themselves from other
specialist providers. To be successful, however, an MSO must be built on a shared
vision of its goals. Considerations of structural, operational, ownership,
antitrust and governance concerns should all follow from that ground. All parties
should recognize that MSOs are best in the long-term; they are not short-term
solutions.
PMID- 10181636
TI - The not-for-profit alternative to PPMCs.
AB - Physician practice management companies (PPMCs) are very fashionable for
physicians seeking long-term security. But not-for-profit alternatives to PPMCs,
namely not-for-profit hospitals, can also provide needed revenue and management
guidance without putting a medical group at the mercy of stockholders. Although
the not-for-profit alternative has its drawbacks--as the fractured partnerships
between some well-known hospitals and medical groups attest--administrators
should not disregard the option.
PMID- 10181637
TI - Public physician practice management companies. Present issues and
recommendations for future viability.
AB - For years, physician practices have been perceived as a "cottage industry". Like
the old fashioned grocery stores, the opinion of some was that they were ripe for
incorporation into organizations which could take advantage of economies of scale
and other synergies. Today, many physicians and organizations are beginning to
rethink their approach to physician practice management companies (PPMCs). Is it
a viable long term strategy for physicians? Does it promote optimal patient care?
Can investor-owned companies realistically respond to the health care needs of
patients while meeting the financial demands of investors? This article seeks to
explore these issues, to examine the current nature of the physician practice
management industry, and discuss what PPMCs might do to add value to the
practices they manage.
PMID- 10181638
TI - Navigating the quality quagmire.
AB - Defining and measuring quality have become business imperatives in many
industries. Quality in health care can be achieved only when appropriate care is
provided. All other outcome measures that presume to define quality are
ineffectual if appropriate care is not delivered first. Without consistently
objective clinical process standards in place, it is impossible to measure
whether health care processes conform to quality benchmarks. Similarly, without a
case-by-case audit trail to determine appropriateness, it is impossible to
document such conformance. Clinical decision support criteria, applied at the
point of care, are a means to support, measure and prove process quality in
health care delivery.
PMID- 10181639
TI - Reviewing practice procedure can improve bottom line.
AB - Anecdotal and statistical sources attest that many hospital-owned physician
practices are either losing money or breaking even. This is alarming for not only
hospital-owned practices, but stand-alone practices, too. However, careful review
of standard billing and coding practice procedures and policies, among other
things, can help reverse that trend.
PMID- 10181640
TI - Critical systems for managed care.
PMID- 10181642
TI - What's your take on percent of premium capitation?
PMID- 10181641
TI - Comparing and selecting patient satisfaction questionnaires.
AB - Demands to measure patient satisfaction have pushed administrators and physician
to select, edit or compare surveys for their practices. However, many surveys are
not as valid or reliable as group practices may expect. Distribution methods and
sample size need careful consideration.
PMID- 10181643
TI - Hospital rounding program: an example.
PMID- 10181645
TI - Compliance culprits.
PMID- 10181644
TI - HL-7 standards only the beginning. Hospital, physician information systems must
be customized for smooth communications.
PMID- 10181646
TI - Practice buyout: structuring the right deal.
AB - Hospitals and physician practice management companies are making offers to many
group practices. It's important for group practice managers to know what to look
for if a buy-out deal is offered. First, make sure the proposed partner will
invest in front-line medicine and has stable management. Secondary considerations
include: making sure buyer and seller goals align, accurately projecting capital
needs and who will pay for them, guarding against provider overcapacity, clearly
delineating parameters for control and limiting bureaucracy.
PMID- 10181647
TI - Implement the medical group revenue function. Create competitive advantage.
AB - This article shows medical groups how they can employ new financial management
and information technology techniques to safeguard their revenue and income
streams. These managerial techniques stem from the application of the medical
group revenue function, which is defined herein. This article also describes how
the medical group revenue function can be used to create value by employing a
database and a decision support system. Finally, the article describes how the
decision support system can be used to create competitive advantage. Through the
wise use of internally generated information, medical groups can negotiate better
contract terms, improve their operations, cut their costs, embark on capital
investment programs and improve market share. As medical groups gain market power
by improving in these areas, they will be more attractive to potential strategic
allies, payers and investment bankers.
PMID- 10181648
TI - Making hard choices. Interview by Pamela L. Moore.
PMID- 10181649
TI - Prepare well for joint venture assessment.
PMID- 10181650
TI - Clinical communication and managed care.
AB - Both physicians and patients are feeling the force of managed care as they
interact. Questions concerning the impact of financial relationships on care
delivery are more public than ever and can form a disturbing subtext in the
examination room. The poor communication that results can be bad for patient care
in and of itself. Training, measurement and consideration of clinical
communication can help bring such issues to the fore, improve the alliance
between physician and patient and help both deal with the vagaries of modern
medicine.
PMID- 10181651
TI - Health care technology and the law.
AB - The health care and computer industries have been booming in the 1990s. Where
they've met, the legal system has been active. Group practice administrators
should especially be aware of three legal areas: regulation of the electronic
transmission of health care records and billing, the Year 2000 Problem and
telemedicine. The Department of Health and Human Services is due to release
standards for electronic transmissions in order to achieve compatability and
patient privacy. Preventing computer problems in 2000 may run up against
copyright laws, and issues about licensure in telemedicine remain an open
question.
PMID- 10181652
TI - Value decision-making: staff benchmarking.
AB - Benchmarking is becoming a more important management tool--especially for setting
staff levels. MGMA data, from Cost Surveys and Physician Compensation and
Productivity Surveys, can help group managers set realistic goals. However, if
taken simply at face value, the data may not provide adequate specificity; it may
not convey the quality and value staff provide a particular organization. This
paper show how to use MGMA data to perform staff benchmarking.
PMID- 10181653
TI - Are contact capitations in your future?
PMID- 10181654
TI - The $40,000 pension Contribution limit.
AB - Tax law changes regarding retirement planning have been massive. Some of the
changes are actually beneficial for physicians and can supplement the business
need to consolidate professional practices and turn the management function over
to organizations dedicated to that purpose. Reasonable physician retirement
planning expectations combined with qualified advisor expertise can go a long way
towards achieving financial independence for physicians at retirement.
PMID- 10181655
TI - Y2K a serious business risk management issue.
PMID- 10181656
TI - Whistle-blower reward programs signal the need to accelerate compliance efforts.
PMID- 10181657
TI - 1998 LTC buyer's guide. The directory of long-term care products & services.
PMID- 10181658
TI - Discharge rule first to recognize subacute.
PMID- 10181659
TI - Subacute providers seek safe landing under PPS. New payment system may stir
turbulence with patient mix and drive providers into alliances.
PMID- 10181660
TI - Real treatment options for incontinence. Condition is no longer a given in the
aging process.
PMID- 10181661
TI - Wound/skin/continence survey.
PMID- 10181662
TI - 'Super-star' DON takes on new role.
PMID- 10181663
TI - Keeping PACE (programs of all-inclusive care for the elderly) with legal issues.
PMID- 10181664
TI - Appealing rates under PPS.
PMID- 10181665
TI - Taking the right pathway. Critical pathways are a road map to care.
PMID- 10181666
TI - Differentials in hospital admission rates for the aboriginal and Torres Strait
islander population in New South Wales.
AB - The indigenous Australian population is well known to have higher rates of
morbidity and mortality than the rest of the Australian population. The study
reported in this paper demonstrates the use of hospital admission data from New
South Wales to monitor the health circumstances and the main areas of
differentials of the indigenous population in relation to access to primary
health care services. The study covers the period from 1989 to 1995. In providing
a statistical approach to analysing large routine databases, the major results
have been to provide estimates of the hospital admission rates by residential
area, sex and age of patient, and to highlight the main differences.
PMID- 10181667
TI - The financial impact of an endoluminal stenting procedure.
AB - This paper reports on a study that examined the financial impact of an
endoluminal grafting procedure for an abdominal aortic aneurysm using the Mialhe
Endoluminal Aortic Stentor. Clinical outcomes were not a focus of this study. The
results of the study suggest that financial impacts of new clinical procedures
can be understood and addressed through planning and greater liaison between
clinicians, coding professionals and clinical costing staff.
PMID- 10181668
TI - The health of Australian children and young adults: recent statistics.
AB - The lack of reliable national statistics to monitor the health of Australian
children and youths is well recognised (Commonwealth Department of Human Services
and Health 1995). There is a clear need to develop this information through a
nationally integrated and coordinated approach. The best way to achieve this
would be to scope the fields of child and youth health information, identify data
gaps and deficiencies, and catalogue the data requirements and needs. The
framework within which this should occur, accompanied by a national child and
youth health information development plan, also needs to be clearly defined. The
Australian Institute of Health and Welfare is undertaking an analysis of the
health of Australian children and youths and a review of available information in
this area. Here we present early work on this project, providing a general
picture of the health of Australian children and youths based on mortality,
morbidity, reported health status and disability statistics. Some information on
the health of indigenous children and young people is also included.
PMID- 10181669
TI - Funding Melbourne's hospitals: some historical moments.
AB - In 1993 the Victorian Government introduced casemix funding as part of its
restructure of the public hospital system. Casemix funding provides a new basis
for government funding according to outcomes. At the same time, restructure of
hospitals allows for a reconsideration of who is eligible to use them. Historical
research into the growth of the public hospital system in Melbourne shows that
attempts to reform the hospital system are as old as the system itself. This
paper argues that the views of hospitals in funding crises and the solutions that
are recommended have more to do with the politics of the day than the economics
of running hospitals.
PMID- 10181670
TI - On complexities of health systems, journals and associations.
PMID- 10181671
TI - Severity variations within DRGs: measurement of hospital effects by use of data
on significant secondary diagnoses and procedures.
AB - The Diagnosis Related Group classification has provided an excellent basis for
enhancing the equity of resource allocation between public acute hospitals.
However, it underestimates the higher levels of severity and consequent
costliness of referral hospitals. This paper describes a practical way of
measuring within-DRG variations in severity, which can be used to increase the
precision of casemix-based funding. It involves the regression of length of stay
against the numbers of significant diagnoses and procedures, and bence the
prediction of additional justified costs. An example is given of its application
to data from South Australian public hospitals.
PMID- 10181672
TI - Specialist adult physicians in the top end of the Northern Territory: an analysis
of their number and roles.
AB - The optimal way of delivering specialist services to rural and remote Australia,
and particularly to remote Aboriginal and Torres Strait Islander communities, is
a matter of keen debate at present, and is being considered by the Australian
Medical Workforce Advisory Committee. This paper contributes to that debate by
considering one specialist medical group, namely adult physicians, and discusses
both their role and optimal number in the Top End of the Northern Territory, in
light of the general workforce literature and recent changes to the organisation
of physician services in the Northern Territory. Models of specialist service
delivery need to be explicit, and organisational methods transparent, if the
service is to be equitable, flexible and accountable to primary care
practitioners.
PMID- 10181673
TI - A new ambulatory classification and funding model for radiation oncology: non
admitted patients in Victorian hospitals.
AB - The Victorian Department of Human Services has developed a classification and
funding model for non-admitted radiation oncology patients. Agencies were
previously funded on an historical cost input basis. For 1996-97, payments were
made according to the new Non-admitted Radiation Oncology Classification System
and include four key components. Fixed grants are based on Weighted Radiation
Therapy Services targets for megavoltage courses, planning procedures (dosimetry
and simulation) and consultations. The additional throughput pool covers
additional Weighted Radiation Therapy Services once targets are reached, with
access conditional on the utilisation of a minimum number of megavoltage fields
by each hospital. Block grants cover specialised treatments, such as
brachytherapy, allied health payments and other support services. Compensation
grants were available to bring payments up to the level of the previous year.
There is potential to provide incentives to promote best practice in Australia
through linking appropriate practice to funding models. Key Australian and
international developments should be monitored, including economic evaluation
studies, classification and funding models, and the deliberations of the American
College of Radiology, the American Society for Therapeutic Radiology and
Oncology, the Trans-Tasman Radiation Oncology Group and the Council of Oncology
Societies of Australia. National impact on clinical practice guidelines in
Australia can be achieved through the Quality of Care and Health Outcomes
Committee of the National Health and Medical Research Council.
PMID- 10181674
TI - Status of total quality management in Australian public health organisations.
AB - Research suggests that there is some confusion among quality improvement managers
about the differences between quality management and traditional quality
assurance. This lack of understanding would appear to be the same among rural and
urban health staff, although there is a higher percentage of staff engaged in
multidisciplinary activities in the rural health services. Education of staff and
commitment from top management would seem to be the factors inhibiting the health
industry from incorporating quality management into their cultures.
PMID- 10181675
TI - Trial of labour versus elective repeat caesarean section: a cost-effectiveness
analysis.
AB - For subsequent births, women who have experienced previous caesarean section face
a choice between elective caesarean section and trial of labour. The study
reported in this paper utilises Australian hospital data to compare birth outcome
and health system costs of these two options. Although trial of labour is more
expensive if the result is an emergency caesarean section, high rates of
successful vaginal delivery mean that, overall, trial of labour is found to be 30
per cent less expensive than elective caesarean section. It is estimated that
trial of labour remains the most cost-effective option as long as less than 68
per cent of women require emergency caesarean section. This study highlights the
potential importance of more accurate information about a broader range of costs
and outcomes in order for stronger conclusions to be drawn.
PMID- 10181676
TI - Provider and consumer perceptions of allied health service needs.
AB - The study reported in this paper compared data from 20 separate focus groups,
representing providers and consumers of health services in the Grampians region,
Victoria, on their perceptions of the allied health service issues in that
region. The results of the study indicated that providers and consumers raised
many similar issues in regard to allied health services--access to allied health
services, service delivery, social and rural issues--but discussed the issues
from different perspectives. The provider discussion was concerned with service
delivery issues and the consumer discussion was focused on broader social issues
which affect health.
PMID- 10181677
TI - Community parenteral therapy project: a pilot study.
AB - The pilot study reported in this paper was devised to develop and compare service
delivery models that would achieve the provision of high quality parenteral
therapy care to patients in the Gold Coast District Health Service community. All
data were collected on 113 patients for a 12-month period, January to December
1996. The study compared the provision of outreach nursing services and
contracted nursing services on measures of satisfaction and cost. The study
showed that patient and carers indicated a preference for community care, medical
officers advocated the benefits of administering parenteral therapies in the
community, general practitioners were interested in managing future community
parenteral therapies, and contracted (nurse) service providers endorsed the
development of a parenteral therapy resource centre. The findings also revealed
considerable potential cost savings in community-based care.
PMID- 10181678
TI - Mental health and general practice: improving linkages using a total quality
management approach.
AB - This paper reports on a project to implement total quality management strategies
to improve the linkages between general practitioners and specialist mental
health services. The project implemented a process of change and objectively
assessed the success of the process. The project involved all mental health staff
(n = 100) in the St George Division of Psychiatry and Mental Health. General
practitioners registered with the St George Division of General Practice were
invited to participate in the change process. The project showed that the
attempts to engage general practitioners in the ongoing care of patients with
chronic mental illness is unlikely to be successful until mental health services
promote general practitioner linkages as an ongoing service goal, relevant at all
levels of delivery.
PMID- 10181679
TI - The Pharmaceutical Benefits Scheme and the shifting paradigm of welfare policy.
AB - This paper describes the design and operation of the Pharmaceutical Benefits
Scheme and then proceeds with an analysis of current policy deliberations which
identifies an extension of the market as predominant trend. The paper
demonstrates that the conditions which historically sustained the scheme are now
present to a lesser extent. The Pharmaceutical Benefits Scheme has functioned as
a universalist welfare program which conferred onto the Commonwealth Department
of Health substantial powers vis-a-vis drug suppliers and professional groups.
This position of dominance has been eroded, with challenges to established
arrangements arising, in particular, from the enhanced bargaining position of
business and wider pressures operating on the Keynesian welfare state.
PMID- 10181680
TI - The health of overseas-born Australians, 1994-1996.
AB - Analysis of mortality, hospital separations and self-reported health indicators
by country of birth group has confirmed that overseas-born populations are
generally in better health than their Australian-born contemporaries. The better
health of the overseas-born may be reflected in both the willingness and
eligibility of individuals to emigrate. Overseas-born individuals were placed
into one of four groups according to place of birth. These included the United
Kingdom and Ireland, Other Europe, Asia and Other. All population groups reported
lower mortality and hospitalisation rates for all causes of disease combined. The
Asian-born population had the lowest mortality rates with 38% less mortality for
males and 30% less for females. Hospitalisation rates were also lower for the
Asian-born, with males and females having 46% and 37% fewer hospital separations
compared to the Australian-born population. However, diabetes mortality was
greater for males and females from Other Europe, Asia and Other regions. Both
males and females from the United Kingdom and Ireland group showed increased
mortality from lung cancer. Mortality and hospitalisation for cervical cancer was
also significantly higher for Asian-born and Other females. The mortality and
hospitalisation data corresponded well with self-reported prevalence of health
related risk factors. For example, self-reported diabetes prevalence was higher
for the Other Europe, Asia and Other groups. Asian and Other females reported
significantly less use of regular Pap smear tests, reflecting their increased
mortality and hospitalisation for cervical cancer. These results support the
finding of past studies that the health of migrants is generally better than that
of the Australian-born population and reflects a 'healthy migrant' effect.
PMID- 10181681
TI - The Health Care Agreements and health: is there any connection?
PMID- 10181682
TI - Making a move on Medicare.
PMID- 10181684
TI - Reform? Rhetoric does not match reality.
PMID- 10181683
TI - We have come to raise Medicare, not to bury it.
PMID- 10181685
TI - The AHA's ideas on health policies for Australia.
PMID- 10181686
TI - Leadership in health: effecting change.
AB - The following article is an edited version of a paper presented to the joint
Australian Private Hospitals Association and Australian Healthcare Association
Conference, 'Caring with Skill', held at Southport, Queensland, on 7-8 April
1998.
PMID- 10181687
TI - Sailing without radar: an excursion in resource allocation.
AB - This paper deals with the knowledge base employed in resource allocation. It
deliberately distinguishes between 'thick-textured' and 'thin-textured'
knowledge. A thick-textured view of change in the health sector accounts for the
history, civic goods and variety of human needs and passions which rationalist
economics defines out as a thin-textured matter of individual choices in a free
market. The narrative material begins with a discussion of health service policy
making in South Australia and elsewhere in the 1980s and 1990s, then proceeds to
a discussion of priority-setting literature, which we regard as thin-textured. We
offer two accounts of approaches to setting priorities in health care which we
think have overcome some of the deficiencies of the thin-textured approach.
PMID- 10181688
TI - The Commonwealth's proposal for the 1998-2003 Health Care Agreements.
AB - The new Health Care Agreements for 1998-2003 are currently being negotiated
between the Commonwealth and State and Territory governments. The Commonwealth's
offer aims to address the major problems associated with the current Agreements,
including cost-shifting incentives and funding rigidities. It has proposed a
funding model whereby admitted and non-admitted patient services are funded on an
output basis. Other aspects of the proposal include funding for quality
enhancement and structural change, and specific funds for mental health and
palliative care. The proposal also aims to achieve a more equal sharing of risks
and benefits between the Commonwealth and the States and Territories. The views
expressed are those of the authors and should not be taken as an official view of
the Department or the Minister. While the authors have had primary responsibility
for the development of the Commonwealth model and the preparation of this paper,
they wish to thank other members of the Health Care Agreement Branch (Heather
Cocks, Ian Macdonald, Elaine Pringle and Shane Wright) for their assistance.
PMID- 10181689
TI - Provider-sponsored organizations: more than just another abbreviation.
PMID- 10181690
TI - Coding: key to compliance.
PMID- 10181691
TI - AlaHA's big victory: the passage of the Volunteer Medical Professional Act.
PMID- 10181692
TI - The state of managed care in Alabama.
PMID- 10181693
TI - Two approaches to service-line management: Community Hospitals Indianapolis and
rural Maine's York Hospital.
PMID- 10181694
TI - Reassessing the number of physicians needed to meet your strategic goals and
contain costs.
PMID- 10181695
TI - Providence Saint Joseph Medical Center in Burbank, CA defragments cancer
services.
PMID- 10181696
TI - Sharp Mission Park Medical Group in Oceanside, CA, gains recognition for access
improvement program.
PMID- 10181697
TI - Integrating new technology with managed care contracting.
AB - The authors of this case study assisted eight teaching hospitals affiliated with
the medical school of New Jersey in a financial analysis of the economic impact
associated with utilization of the coronary artery stent implant. Consisting of a
former health system CEO, a financial consultant/hospital trustee and an
experienced hospital executive, this team shared their findings with medical and
administrative staff to develop best practice models. The results of a new
extended patient follow-up study contrasting outcomes and cost for stent vs. PTCA
procedures will be reported later this year.
PMID- 10181698
TI - Providing health care for the uninsured in America: the States and public policy.
PMID- 10181699
TI - What is cardiac rehab?
PMID- 10181700
TI - The "commoditization" of medicine.
PMID- 10181701
TI - Quality 101. Part 2.
PMID- 10181702
TI - Balanced scorecard as a framework for driving performance in managed care
organizations.
AB - Managed care organizations in a highly competitive environment constantly face
the pressure of improving their financial performance. At the same time,
customers of the organization expect the organization to deliver high-quality
outcomes and improve customer service. Payers expect the organization to develop
innovative new products to meet their needs. This article presents an approach
called "Balanced Scorecard" for measurement, development of strategy, and
performance improvement in a managed care organization.
PMID- 10181703
TI - Strategic implications of developing integrated levels of care.
AB - Current reimbursement mechanisms provide incentives for health systems to develop
or have access to and utilize a variety of postacute care settings, but not
necessarily to provide integrated care across those settings. While most health
care systems speak of providing integrated care, few actually do. Several market
forces are now making health systems reexamine how care is provided across the
continuum and creating the incentives for health systems to integrate care across
each level within the continuum. This article describes how to develop integrated
levels of care and the strategic implications of doing so.
PMID- 10181704
TI - Keeping pace: video communications in a managed care environment. Interview by
Thomas A. Rasmussen.
AB - A number of health care provider organizations, particularly those with
geographically dispersed personnel, are utilizing the video medium to improve
organizational performance. The key attributes of the video medium are uniformity
of education delivery to multiple sites, the ability to deliver information in a
timely manner, the ability to visually portray best practices for all to see, and
the convenience for end-users. While the executives interviewed for this article
aren't aware of any published research specifically documenting the linkage
between video education and improved organizational performance, the panelists
believe that informed health care professionals inherently contribute to improved
organizational performance and that video education is a prudent investment of
resources.
PMID- 10181705
TI - Managed care organization liabilities.
AB - While certain efficiencies and cost savings have been achieved, Managed Care
Organizations (MCOs) have risk exposures never before considered. MCOs provide a
number of services for their clients. Specifically, they are involved in
credentialing, network development, utilization review, and the hiring and firing
of physicians and other allied medical professionals subject to rather complex
and detailed contractual arrangements. The insurance industry has responded to
the increase in claim exposure associated with the aforementioned activities by
providing any number of insurance products. Depending on the insurance provider,
a number of different coverages are available. The final decision as to which
coverage to purchase will be governed by the risks associated with a particular
MCO, contractual protections, available cash flow, protections under federal and
state laws. The point of this article is to apprise MCOs of the claims now
starting to develop against MCOs as well as alternative insurance products that
can be purchased in order to protect both the firm's assets as well as those of
individual directors and officers.
PMID- 10181706
TI - Deregulation in New York State--an update.
PMID- 10181707
TI - Emerging legal issues.
PMID- 10181708
TI - Technology and managed care meet strategy.
AB - A complete technology plan has a managed care component to support your segment's
managed care strategy. As your segment interfaces with managed care components
from other segments, your technology will need the flexibility to provide
management information across all segment interfaces.
PMID- 10181709
TI - German health system slow to change.
PMID- 10181710
TI - Customer centered health care: why managed care organizations must capitalize on
new technology to build brands and customer loyalty.
AB - Now, more than ever, health care organizations are desperately trying to reach
out to customers and establish stronger relationships that will generate
increased loyalty and repeat business. As technology, like the Internet and
related mediums, allow us to do a better job of managing information and
communication, health care executives must invest the time and resources
necessary to bring these new advances into the day-to-day operations of their
businesses. Those that do will have a head start in building their brand and
their customer loyalty.
PMID- 10181711
TI - Hospital disaster preparedness: meeting a requirement or preparing for the worst?
AB - Too many of our nation's hospitals have been become complacent over disaster
preparedness. They develop a document to meet a licensure requirement or a joint
Commission on Accreditation of Healthcare Organizations standard. The language is
minimal and when the document is exercised, only a few portions (personnel recall
and mass casualty, in particular) are tested. It would benefit hospitals to take
time to talk to those recently effected by floods, earthquakes or hurricanes, so
that they would learn that to be really prepared to face and survive a disaster,
extensive, in-depth planning must take place.
PMID- 10181712
TI - Privacy Act of 1974; report of new system--HCFA. Notice of new system of records.
AB - In accordance with the requirements of the Privacy Act of 1974, we are proposing
to establish a new system of records, called "End-Stage Renal Disease (ESRD)
Managed Care Demonstration System," HHS/HCFA/OSP No. 09-70-0067. We have provided
background information about the proposed new system in the SUPPLEMENTARY
INFORMATION section below. Although the Privacy Act requires only that the
"routine uses" portion of the system be published for comment, HCFA invites
comments on all portions of this notice.
PMID- 10181713
TI - Privacy Act of 1974; report of new system--HCFA. Notice of new system of records.
AB - In accordance with the requirements of the Privacy Act of 1974, we are proposing
to establish a new system of records, called the "National Provider System
(NPS)," HHS/HCFA/OIS No. 09-70-0008. We have provided background information
about the proposed system in the "Supplementary Information" section below. Both
institutional (e.g., hospitals, skilled nursing facilitaties) and individually
identifiable (e.g., physicians and other practitioners) providers are included in
the NPS database. The institutional providers' data are covered by section 1106
of the Social Security Act and the Freedom of Information Act, while the
individually identifiable providers' data are also covered by the Privacy Act of
1974. Although the Privacy Act requires only that the "routine uses" portion of
the system be published for comment, HCFA invites comments on all portions of
this notice. See "Effective Dates" for comment period.
PMID- 10181714
TI - Medical devices; reclassification and codification of vitamin D test system--FDA.
Final rule.
AB - The Food and Drug Administration (FDA) is announcing that it has issued an order
in the form of a letter to INCSTAR Corp. reclassifying INCSTAR 25-Hydroxyvitamin
D 125I Radioimmunoassay (RIA). This radioimmunoassay device is intended for use
in clinical laboratories for the quantitative determination of 25-hydroxyvitamin
D (25-OH-D) and other hydroxylated metabolites of vitamin D in serum or plasma to
be used in the assessment of vitamin D sufficiency. The device and substantially
equivalent devices of this generic type were reclassified from class III
(premarket approval) to class II (special controls). Accordingly, the order is
being codified in the Code of Federal Regulations.
PMID- 10181715
TI - Medicare program; peer review organization contracts: solicitation of statements
of interest from in-state organizations--Alaska, Delaware, the District of
Columbia, Hawaii, Idaho, Illinois, Kentucky, Maine, Nebraska, Nevada, South
Carolina, Vermont, and Wyoming--HCFA. Notice.
AB - This notice, in accordance with section 1153(i) of the Social Security Act, gives
at least 6 months' advance notice of the expiration dates of contracts with out
of-State Utilization and Quality Control Peer Review Organizations. It also
specifies the period of time in which in-State organizations may submit a
statement of interest so that they may be eligible to compete for these
contracts.
PMID- 10181716
TI - Medical devices; humanitarian use of devices--FDA. Direct final rule; withdrawal.
AB - The Food and Drug Administration (FDA) published, in the Federal Register of
April 17, 1998 (63 FR 19185), a direct final rule to implement the amendments to
the humanitarian use devices provision of the Federal Food, Drug, and Cosmetic
Act (the act), as amended by the Food and Drug Administration Modernization Act
of 1997 (FDAMA). The comment period closed July 1, 1998. FDA is withdrawing the
direct final rule because the agency received significant adverse comment.
PMID- 10181717
TI - Biological products regulated under Section 351 of the Public Health Services
Act; implementation of biologics license; elimination of establishment license
and product license--FDA. Proposed rule.
AB - The Food and Drug Administration (FDA) is proposing to amend the biologics
regulations to eliminate references to establishment licenses and product
licenses for all products regulated under the Public Health Service Act (PHS
Act). In lieu of filing an establishment license application (ELA) and product
license application (PLA) in order to market a biological product in interstate
commerce, a manufacturer would file a single biologics license application (BLA)
with the agency. Upon approval of the BLA, a manufacturer would receive a
biologics license to market the product in interstate commerce. This action is
part of FDA's continuing effort to achieve the objectives of the President's
"Reinventing Government" initiatives and is intended to reduce unnecessary
burdens for industry without diminishing public health protection. This action
also proposes regulations to implement certain sections of the Food and Drug
Administration Modernization Act of 1997 (FDAMA).
PMID- 10181718
TI - Medicare program; changes to the hospital inpatient prospective payment systems
and fiscal year 1999 rates--HCFA. Final rule.
AB - We are revising the Medicare hospital inpatient prospective payment systems for
operating costs and capital-related costs to implement applicable statutory
requirements, including section 4407 of the Balanced Budget Act of 1997 (BBA), as
well as changes arising from our continuing experience with the systems. In
addition, in the addendum to this final rule, we describe changes in the amounts
and factors necessary to determine rates for Medicare hospital inpatient services
for operating costs and capital-related costs. These changes are applicable to
discharges occurring on or after October 1, 1998. We also set forth rate-of
increase limits as well as changes for hospitals and hospital units excluded from
the prospective payment systems. Finally, we are implementing the provisions of
section 4625 of the BBA concerning payment for the direct costs of graduate
medical education.
PMID- 10181719
TI - Medicare and Medicaid programs; surety bond requirements for home health agencies
-HCFA. Final rule.
AB - This final rule revised Medicare and Medicaid regulations concerning surety bond
requirements published in the Federal Register (63 FR 29648) on June 1, 1998.
Those regulations specified submission compliance dates for all home health
agencies (HHAs) to furnish a surety bond to HCFA and/or to the State Medicaid
agency. This rule removes those submission compliance dates.
PMID- 10181720
TI - Failure by certain charitable organizations to meet certain qualification
requirements; taxes on excess benefit transactions--IRS. Notice of proposed
rulemaking.
AB - This document contains proposed regulations relating to the excise taxes on
excess benefit transactions under section 4958 of the Internal Revenue Code
(Code), as well as certain amendments and additions to existing Income Tax
Regulations affected by section 4958. Section 4958 was enacted in section 1311 of
the Taxpayer Bill of Rights 2. Section 4958 generally is effective for
transactions occurring on or after September 14, 1995. Section 4958 imposes
excise taxes on transactions that provide excess economic benefits to
disqualified persons of public charities and social welfare organizations. The
proposed regulations clarify certain definitions and rules contained in section
4958.
PMID- 10181721
TI - Personal Responsibility and Work Opportunity Reconciliation Act of 1996 (PRWORA);
interpretation of "federal public benefit"--HHS. Notice with comment period.
AB - This notice with comment period interprets the term "Federal public benefit" as
used in Title IV of the Personal Responsibility and Work Opportunity
Reconciliation Act of 1996 (PRWORA), Pub. L. 104-193, and identifies the HHS
programs that provide such benefits under this interpretation. According to
section 401 if PRWORA, aliens who are not "qualified aliens" are not eligible for
any "Federal public benefit," unless the "Federal public benefit" falls within a
specified exception. A "Federal public benefit" includes "any grant, contract,
loan, professional license, or commercial license" provided to an individual, and
also "any retirement, welfare, health, disability, public or assisted housing,
postsecondary education, food assistance, unemployment benefit, or any other
similar benefit for which payments or assistance are provided to an individual,
household, or family eligibility unit." Under section 432, providers of a non
exempt "Federal public benefit" must verify that a person applying for the
benefit is a qualified alien and is eligible to receive the benefit. The HHS
programs that provide "Federal public benefits" and are not otherwise excluded
from the definition by the exceptions provided in section 401(b) are: Adoption
Assistance Administration on Developmental Disabilities (ADD)-State Developmental
Disabilities Councils (direct services only) ADD-Special Projects (direct
services only) ADD-University Affiliated Programs (clinical disability assessment
services only) Adult Programs/Payments to Territories Agency for Health Care
Policy and Research Dissertation Grants Child Care and Development Fund Clinical
Training Grant for Faculty Development in Alcohol & Drug Abuse Foster Care Health
Profession Education and Training Assistance Independent Living Program Job
Opportunities for Low Income Individuals (JOLI) Low Income Home Energy Assistance
Program (LIHEAP) Medicare Medicaid (except assistance for an emergency medical
condition) Mental Health Clinical Training Grants Native Hawaiian Loan Program
Refugee Cash Assistance Refugee Medical Assistance Refugee Preventive Health
Services Program Refugee Social Services Formula Program Refugee Social Services
Discretionary Program Refugee Targeted Assistance Formula Program Refugee
Targeted Assistance Discretionary Program Refugee Unaccompanied Minors Program
Refugee Voluntary Agency Matching Grant Program Repatriation Program Residential
Energy Assistance Challenge Option (REACH) Social Services Block Grant (SSBG)
State Child Health Insurance Program (CHIP) Temporary Assistance for Needy
Families (TANF) While all of these programs provide "Federal public benefits"
this does not mean that all benefits or services provided under these programs
are "Federal public benefits." As discussed in sections II and III below, some
benefits or services under these programs may not be provided to an "individual,
household, or family eligibility unit" and, therefore, do not constitute "Federal
public benefits" as defined by PRWORA.
PMID- 10181722
TI - Verification of eligibility for public benefits--INS. Proposed rule.
AB - This rule amends the Immigration and Naturalization Service ("Service")
regulations by establishing a new part requiring certain entities that provide
Federal public benefits (with certain exceptions) to verify, by examining alien
applicants' evidence of alien registration and by using a Service automated
verification system that the applicants are eligible for the benefits under
welfare reform legislation. The rule also sets forth procedures by which a State
or local government can verify whether an alien applying for a State or local
public benefit is a qualified alien, a nonimmigrant, or an alien paroled into the
United States for less than 1 year, for purposes of determining whether the alien
is eligible for the benefit. In addition, the rule establishes procedures for
verifying the U.S. nationality of individuals applying for benefits in a fair and
nondiscriminatory manner.
PMID- 10181723
TI - Revisions to the general safety test requirements for biological products--FDA.
Direct final rule: confirmation in part and withdrawal in part.
AB - The Food and Drug Administration (FDA) is confirming in part and withdrawing in
part the provisions in the direct final rule that published in the Federal
Register of April 20, 1998, to revise the general safety test (GST) requirements
for biological products. FDA is confirming the part of the rule about which no
significant adverse comment was received and withdrawing the part about which
significant adverse comment was received.
PMID- 10181724
TI - Clinical studies of safety and effectiveness of orphan products; availability of
grants; request for applications--FDA. Notice.
AB - The Food and Drug Administration (FDA) is announcing changes to its Orphan
Products Development (OPD) grant program for fiscal year (FY) 1999. The previous
announcement of this program, which was published in the Federal Register of July
9, 1997, is superseded by this announcement. In the future, a new announcement
will be published annually.
PMID- 10181725
TI - Medical devices; reports of corrections and removals--FDA. Direct final rule.
AB - The Food and Drug Administration (FDA) is amending its regulations that govern
reports of corrections and removals of medical devices to eliminate the
requirement for distributors to make such reports. The amendments are being made
to implement provisions of the Federal Food, Drug, and Cosmetic Act (the act), as
amended by the Food and Drug Administration Modernization Act of 1997 (FDAMA).
FDA is publishing these amendments in accordance with its direct final rule
procedures. Elsewhere in this issue of the Federal Register, FDA is publishing a
companion proposed rule under FDA's usual procedures for notice and comment to
provide a procedural framework to finalize the rule in the event the agency
receives any significant adverse comment and withdraws the direct final rule.
PMID- 10181726
TI - Medicaid and Title IV-E programs; revision to the definition of an unemployed
parent--Administration for Children and Families (ACF) and HCFA. Final rule with
comment period.
AB - The Personal Responsibility and Work Opportunity Reconciliation Act of 1996
(PRWORA) transformed the nation's welfare system into one that requires work in
exchange for time-limited assistance. The law eliminated the Aid to Families with
Dependent Children (AFDC) program and replaced it with the Temporary Assistance
for Needy Families (TANF) program. The law provides States flexibility to design
their TANF programs in ways that strengthen families and promote work,
responsibility, and self-sufficiency while holding them accountable for results.
Many States are using this flexibility to provide welfare to work assistance to
two parent families, which was more difficult to do under the old welfare rules.
However, pre-existing regulations regarding the definition of "unemployed parent"
prevent some States from providing intact families with health insurance to help
them stay employed. This rule will eliminate this vestige of the old welfare
system in order to promote work, strengthen families, and simplify State program
administration. In general under PRWORA, States must ensure that families who
would have qualified for Medicaid health benefits under the prior welfare law are
still eligible. While under the previous law receipt of AFDC qualified families
for Medicaid, the new statute does not tie receipt of TANF to Medicaid. Instead,
subject to some exceptions, Medicaid eligibility for families and children now
depends upon whether a family would have qualified for AFDC under the rules in
effect on July 16, 1996. Similarly, Federal foster care eligibility depends on
whether the child would have qualified for AFDC under the rules in effect on July
16, 1996. In order for a family to qualify for assistance under the pre-PRWORA
AFDC rules, its child had to be deprived of parental support or care due to the
death, absence, incapacity, or unemployment of a parent. Two parent families
generally qualified only under the "unemployment" criterion which was narrowly
defined in the AFDC regulations. In this final rule with comment, we are amending
these regulations to provide States with additional flexibility to provide
Medicaid coverage to two parent families, facilitate coordination among the TANF,
Medicaid and foster care programs, increase incentives for fulltime work, and
allow States to eliminate inequitable rules that are a disincentive to family
unity.
PMID- 10181727
TI - Medical devices; reports of corrections and removals; companion to direct final
rule--FDA. Proposed rule.
AB - The Food and Drug Administration (FDA) is proposing to amend its regulations
governing reports of corrections and removal of medical devices to eliminate the
requirement for distributors to make such reports. This proposed rule is a
companion document to the direct final rule published elsewhere in this issue of
the Federal Register. The amendments are being made to implement provisions of
the Federal Food, Drug and Cosmetic Act (the act), as amended by the Food and
Drug Administration Modernization Act of 1997 (FDAMA). This companion proposed
rule is issued under FDAMA and the act as amended.
PMID- 10181728
TI - Solicitation of information and recommendations for developing OIG compliance
program guidance for the durable medical equipment industry--HHS. Notice.
AB - This Federal Register notice seeks the input and recommendations of interested
parties into the OIG's development of a compliance program guidance for the
durable medical equipment (DME) industry, its providers and suppliers. Many
providers and provider organizations have expressed an interest in better
protecting their operations from fraud and abuse. Previously, the OIG has
developed compliance program guidances for hospitals, clinical laboratories and
home health agencies. In order to provide clear and meaningful guidance to those
segments of the health care industry involved in the supply and distribution of
DME, we are soliciting comments, recommendations and other suggestions from
concerned parties and organizations on how best to develop compliance program
guidance and reduce fraud and abuse within the DME industry.
PMID- 10181729
TI - Publication of the OIG compliance program guidance for home health agencies--OIG.
Notice.
AB - This Federal Register notice sets forth the recently issued Compliance Program
Guidance for Home Health Agencies developed by the Office of Inspector General
(OIG) in cooperation with, and with input from, several provider groups and
industry representatives. Many home health care providers have expressed interest
in better protecting their operations from fraud and abuse through the adoption
of a voluntary compliance program. The OIG has previously developed and published
compliance program guidances focused on the clinical laboratory and hospital
industries (62 FR 9435, March 3, 1997 and 63 FR 8987, February 23, 1998,
respectively). We believe that the development of this compliance program
guidance for the home health industry will continue as a positive step towards
promoting a higher level of ethical and lawful conduct throughout the entire
health care community.
PMID- 10181730
TI - Fetal abuse laws gain favor.
PMID- 10181731
TI - Health care reform hits the road.
PMID- 10181732
TI - Some SNFs surprised by no Part B add-on; HCFA re-examining calculations.
PMID- 10181733
TI - The next step in managed care contracting: capitation in a subacute environment.
PMID- 10181734
TI - 24-hour tracking, correct scoring of activities of daily living critical to
proper PPS payments.
PMID- 10181735
TI - Celebrating innovation. AAHP awards plans that lead the way in improving
childhood and adult immunization.
PMID- 10181736
TI - Preserving the role of the family doctor.
PMID- 10181737
TI - Health plans strive for diversity.
PMID- 10181738
TI - Utilization management: a new generation.
PMID- 10181739
TI - Bringing it all back home. Telemedicine bridges the distance between patient and
provider.
PMID- 10181740
TI - Social HMOs: making seniors' lives better at home.
PMID- 10181741
TI - State-issued report cards.
PMID- 10181742
TI - Tomorrow's doctors.
PMID- 10181743
TI - By the numbers. Managed care techniques: the physician view.
PMID- 10181744
TI - The CEO's perspective.
PMID- 10181746
TI - Patient-provider communication and managed care.
PMID- 10181745
TI - By the numbers. Managed care highlights.
PMID- 10181747
TI - Using technology to target disease management approaches.
PMID- 10181748
TI - Making health care better.
PMID- 10181749
TI - 20/20 vision care.
PMID- 10181750
TI - Rethinking length-of-stay mandates.
PMID- 10181751
TI - Pharmacoeconomics: determining the value of drug therapy.
PMID- 10181752
TI - Literacy and good health.
PMID- 10181753
TI - Cultivating better relationships with teens.
PMID- 10181754
TI - The new American health system.
PMID- 10181755
TI - Taking pages from other notebooks. Managed care executives turn to other
industries for ideas on how to improve member service and satisfaction.
PMID- 10181756
TI - Making the case for evidence-based medicine.
PMID- 10181757
TI - Stopping the violence.
PMID- 10181758
TI - From turnover to teamwork.
PMID- 10181759
TI - How to conduct an energy audit.
PMID- 10181760
TI - Competencies for geriatric care. Sensitivity to the aging process is a key
element.
PMID- 10181761
TI - Food therapy for seniors.
PMID- 10181762
TI - Entrepreneurial pursuits. Words of wisdom from successful self-employed
dietitians.
PMID- 10181763
TI - Tips for improving survey results. Effective communication is a key factor.
PMID- 10181764
TI - JCAHO revises safety standards. "Environment of Care" chapter conforms to NFPA
and OSHA regulations.
PMID- 10181765
TI - Nutrition consultants in private practice. Where they work and what they do.
PMID- 10181766
TI - Food and nutrition services for adults. Fourth in a series on age-specific
competencies.
PMID- 10181767
TI - When you look in your crystal ball, do you see a PSO in your future?
AB - This is the first part of a two-part series on provider-sponsored organizations
(PSOs) and what providers should consider before establishing one. The PSO
regulations, which were not available at press time, will be discussed in a
future issue. Other future topics will include an explanation of PSO solvency
standards, tips on marketing a Medicare product, and information about why you
need a compliance plan before starting a PSO.
PMID- 10181768
TI - Test PSO waters before jumping in.
PMID- 10181769
TI - Learn from experience of IPA targeted in antitrust suit. Mesa County IPA
prevailed, but making changes.
PMID- 10181771
TI - Peer review process helps keep quality high.
PMID- 10181770
TI - Clip this guide on what triggers FTC investigation.
PMID- 10181772
TI - Stick to key strategies in vertical integration.
PMID- 10181773
TI - Comparative measures improve diabetes care.
PMID- 10181774
TI - Patient complaints can help practices improve.
PMID- 10181775
TI - HEDIS measures can make practices almost perfect.
PMID- 10181776
TI - Benchmarking helps ease patients', hospital's pain.
PMID- 10181777
TI - What should you do if bad publicity threatens your hospital's reputation?
PMID- 10181778
TI - Finding Mr. or Ms. Right for your hospital.
PMID- 10181779
TI - Terminating an employee with tact.
PMID- 10181781
TI - Stakes rise for HEDIS with new accreditation rules.
PMID- 10181780
TI - Stuck between a rock and a hard place. Refereeing employee-physician disputes
tactfully.
PMID- 10181782
TI - Want to track outcomes by phone? Press 1.
PMID- 10181783
TI - Practices can use hospital compliance guidelines.
PMID- 10181784
TI - What makes a good leader? The answer can surprise some doctors.
AB - Not all leaders are born. Leader Labs were developed by Sutter Health so its
doctors could hone their leadership skills--or discover the leadership track
wasn't what they wanted after all. Peers, bosses, and subordinates provide an
involved and honest description of the doctor's strengths and weaknesses. The
doctor responds to that feedback and develops and action plan, with the help of
Leader Lab's facilitators. During the three-day process, some doctors discover
that they don't actually want to be leaders at all; such a discovery should not
be viewed as a waste of time, but actually a way to save time and effort over the
long run.
PMID- 10181785
TI - HCFA institutes new PA payment rules.
PMID- 10181786
TI - Change practice patterns without ruffling feathers.
AB - When physicians act as change agents among their peers, they encounter many of
the same resistances that quality improvement professionals face. Practice
guidelines are one of several keys to influencing doctors to bring their
utilization rates in line with their peers. Good data are another must-have tool
for achieving physician buy-in on changing care practices. Most doctors pay
attention to peer influence and pressure when it comes to changing their familiar
care practices. Physicians report that sometimes the motivation to change springs
from the desire to stave off external controls by payers and the government.
PMID- 10181787
TI - In physician profile data, home-grown is best.
PMID- 10181788
TI - Merger failure means change for market. PPMCs are regrouping, not dying.
PMID- 10181789
TI - OIG ruling puts common fee arrangement in question. PPMCs: not dead yet, but
facing major changes.
AB - A recent opinion by the Office of Inspector General has found that physician
groups that pay management companies a percentage of revenue for marketing and
network development may be in violation of federal anti-kickback statutes.
Although it affects only the practice that sought the opinion, this decision
could spark major changes in the way PPMCs and practices structure fee
arrangements. In the future, more emphasis will have to be put on safeguards
against abusive billing practices and over-utilization. The future of PPMC
arrangement may be fixed fee agreements, but these, too, will have to be
customized to each particular practice-PPMC relationship.
PMID- 10181790
TI - The art and science of cross-border management.
AB - Mergers, acquisitions, and even plain expansion means that more practices operate
in multiple states. But there are different employment laws in each state, and
benefits such as health insurance can vary from market to market. The first step
to effective management of staffs across state lines is to work through the maze
of legal differences. Then you have to make sure that the benefits you give to
all your staff members are roughly equivalent. That may mean phasing out some
benefits at one location, or providing completely new ones in another. Once you
get through the nitty gritty of legal and benefit analysis, you have to work on
remote management issues. It can be difficult to merge the cultures at two
practices, and even more difficult to get the new staff to trust you. These
issues can often take longer to resolve than the legal ones.
PMID- 10181792
TI - Are they patients or customers?
PMID- 10181791
TI - Are the solo practitioner's days numbered?
PMID- 10181793
TI - Doctors react swiftly to evidence of variation.
PMID- 10181794
TI - Survey says: academic practices follow the norm.
PMID- 10181795
TI - Interview with Elizabeth Dole, President, American Red Cross. Interview by James
A. Johnson.
PMID- 10181796
TI - "Profiling" managed care.
PMID- 10181797
TI - Ethics and decision making in healthcare.
PMID- 10181798
TI - The lessons of a profession: 25 years later.
PMID- 10181799
TI - The effect of managed care on hospital marketing orientation.
AB - Marketing is a central activity of modern organizations. To survive and succeed,
organizations must know their markets, attract sufficient resources, convert
these resources into appropriate services, and communicate them to various
consuming publics. In the hospital industry, a marketing orientation is currently
recognized as a necessary management function in a highly competitive and
resource-constrained environment. Further, the literature supports a marketing
orientation as superior to other orientation types, namely production, product
and sales. In this article, the results of the first national cross-sectional
study of the marketing orientation of U.S. hospitals in a managed care
environment are reported. Several key lessons for hospital executives have
emerged. First, to varying degrees, U.S. hospitals have adopted a marketing
orientation. Second, hospitals that are larger, or that have developed strong
affiliations with other providers that involve some level of financial
interdependence, have the greatest marketing orientation. Third, as managed care
organizations have increased their presence in a state, hospitals have become
less marketing oriented. Finally, contrary to prior findings, for-profit
institutions are not intrinsically more marketing oriented than their not-for
profit counterparts. This finding is surprising because of the traditional role
of marketing in non-health for-profit enterprises and management's greater
emphasis on profitability. An area of concern for hospital executives arises from
the finding that as managed care pressure increases, hospital marketing
orientation decreases. Although a marketing orientation is posited to lead to
greater customer satisfaction and improved business results, a managed care
environment seems to force hospitals to focus more on cost control than on
customer satisfaction. Hospital executives are cautioned that cost-cutting, the
primary focus in intense managed care environments, may lead to short-term gains
by capturing managed care business, but may not be sufficient for long-term
success and survival. Understanding consumer needs and perceptions, and using
appropriate marketing strategies to ensure greater customer satisfaction and
repeat business, will be among the key tasks for hospital executives in the
future.
PMID- 10181800
TI - Assessing the extent of integration achieved through physician-hospital
arrangements.
AB - In this article we examine management service organizations (MSOs), physician
hospital organizations (PHOs), hospital-affiliated independent practice
associations (IPAs), and hospital-sponsored "group practices without walls"
(GPWWs) that allow physicians to retain their practices and link hospitals and
health systems to physicians through contractual arrangements. Also examined were
medical foundations (MFs), integrated salary models (ISMs), and integrated health
organizations (IHOs) that own the physical assets of physician practices and
contract with payors for physician and hospital services. The research provides
several new insights for understanding the structure and process of physician
hospital integration. It was found that the extent of processual integration in
physician-hospital organizational arrangements can be measured along six
dimensions: administrative and practice management services; physician financial
risk-sharing; joint ventures to create new services; computer linkages; physician
involvement in strategic planning; and salaried physician arrangements. These
dimensions are consistent with the conceptual and empirical dimensions developed
by others. These findings refute the notion raised by some industry observers
that the new physician-hospital organizational models simply formalize
integrative activities already in place. Earlier studies from the 1980s reported
that hospitals integrated physicians through involvement in governance, capital
planning, and the provision of practice management services. In contrast, we
found that current integration.
PMID- 10181801
TI - The balanced scorecard: a potent tool for energizing and focusing healthcare
organization management.
AB - The current environment for healthcare organizations contains many forces
demanding unprecedented levels of change. These forces include changing
demographics, increased customer expectations, increased competition, and
intensified governmental pressure. Meeting these challenges will require
healthcare organizations to undergo fundamental changes and to continuously seek
new ways to create future value. This article provides explanation of a potent
new management tool-the balanced scorecard-that can be used by healthcare
organizations to meet these challenges. The article also presents the opinions of
many high-level healthcare administrators that the balanced scorecard can be
highly beneficial to healthcare organizations. It also summarizes these
administrators' suggestions regarding the goals and measures that can make up an
effective scorecard for a hospital as a whole, as well as for a specific subunit
of a hospital. Interestingly, while no published report of balanced scorecard
implementations in healthcare organizations exists, a number of administrators
stated that they had fully implemented systems similar to the scorecard. These
actions can be considered support for the scorecard's potential usefulness; at
the same time, they suggest that some sharing of experiences will likely be
available in the future. As all administrators are well aware, moving from
concept to practice is often difficult. While the article includes some
suggestions for scorecard development and implementation, each organization must
engage in the full range of activities, from defining its mission to the
selection of goals and strategies, and develop its own unique scorecard to assist
progress toward the selected goals. As a starting point, Table 3 provides a
timeline of some general events that may be common to all organizations during
this process.
PMID- 10181802
TI - Waiting for satisfaction.
AB - This case study documents McKay-Dee Hospital Center's search for a solution for
low patient satisfaction scores concerning wait times for surgery patients
entering McKay-Dee's Same Day Department. Unable to expand to an appropriate size
for present patient flow, the operating room/recovery room committee reviewed
data on patient wait times at a physician level to determine an alternate
solution to expansion. Data were gathered and refined, definitions were
interpreted, and various steps in the scheduling processes were delineated,
clarifying several issues that affected patient wait times. By studying the data
in a committee setting rather than focusing on the human aspect, detrimental
patterns such as late schedule changes and "catch-all procedures" were identified
and logical solutions were suggested. In this manner, preoperative wait time
targets were appropriately set, surgeons and staff were counseled, and surgical
scheduling became more accurate. The result was a dramatic rise in patient
satisfaction scores concerning preoperative wait times.
PMID- 10181803
TI - Hospitals call bad debt plan a bad call.
PMID- 10181804
TI - GAO verdict on hospital sales. Government study debunks myths about private
hospitals.
PMID- 10181805
TI - More Medicare? Clinton's early retiree proposal.
PMID- 10181806
TI - Half way to a new Columbia/HCA.
PMID- 10181807
TI - Is disease management paying off?
PMID- 10181808
TI - Keep physician productivity high through communication, incentives.
PMID- 10181809
TI - Providing physician payment information takes mystery out of motivation.
PMID- 10181810
TI - Two efforts moving toward outcomes standardization.
PMID- 10181811
TI - Patient record security starts with privacy rights.
PMID- 10181812
TI - Measuring the effectiveness of care.
PMID- 10181813
TI - Joint marketing success rests on long-term relations.
PMID- 10181814
TI - Making a bad deal better: contract renegotiation strategies.
PMID- 10181815
TI - The little engine that could and slowly will: a bureaucrat's view.
PMID- 10181816
TI - The little engine that could: Medicaid at the millenium.
AB - The Medicaid program is little understood and, often, even less liked. It has
suffered from poor design, unintended consequences, massive cost increases,
provider hostility, and the slings and arrows of political fortune. Nonetheless,
it provides at least some coverage to 1 in 8 Americans and has been a hotbed of
health policy experimentation--often for better, sometimes for worse. As it
stands at yet another crossroads, its fate is uncertain; yet there does not seem
to be anything that could replace it, save a level of social cruelty this nation
is so far not ready to accept. The question, then, is how to make the best of
Medicaid's tenuous situation--and what we might do to improve it.
PMID- 10181817
TI - The little engine still can (if switched off the mainstream track)
PMID- 10181819
TI - Clinical negligence. Tender is the invite.
PMID- 10181818
TI - Medicaid's future: a political perspective.
PMID- 10181820
TI - Public consultation. Question time.
PMID- 10181821
TI - Patient records. Confidence boost.
PMID- 10181822
TI - Construction. Making good.
PMID- 10181823
TI - Group action. United they stand and fall.
PMID- 10181824
TI - EU law. Passport to priority.
PMID- 10181825
TI - Fraud. Cutting your losses.
PMID- 10181826
TI - Reality cheque.
PMID- 10181827
TI - Infertility treatment. The cost of living.
PMID- 10181829
TI - Savvy planners morph three buildings into one-stop health shop.
PMID- 10181828
TI - General practice. To whom do you refer?
AB - The quality of trusts' communications and administration systems is a key
influence in GPs' referral patterns. The local hospital will always have an
advantage in attracting referrals from local GPs. GPs view the calibre of
clinical staff as important, but not overwhelmingly so. Once referral links are
made, they are almost impossible to change.
PMID- 10181830
TI - Go for the gold. Put some muscle in the bottom line. Think 'fitness center.'.
PMID- 10181831
TI - Debugging antimicrobial regulation. Interview by Laura Souhrada.
PMID- 10181832
TI - Match game. Find out how your energy use stacks up against other facilities.
PMID- 10181834
TI - Is your clean team off track? Time to set standards.
PMID- 10181833
TI - FYI: a snapshot of the JCAHO's life safety code.
PMID- 10181835
TI - Patient-friendly design: the right Rx for the ED blues.
PMID- 10181836
TI - Color schemers.
PMID- 10181837
TI - Matchmakers.
PMID- 10181838
TI - Survival of the certified. Certification gets facility managers and mechanics a
ticket to ride.
PMID- 10181839
TI - Check out these hot tips on textile services safety.
PMID- 10181840
TI - Tanks a lot! Get ready to meet UST (underground storage tank) deadline.
PMID- 10181841
TI - Looking at care from the inside out: a conceptual approach to geriatric care.
AB - Today, managing care from the "outside in" is the predominant model for changing
health care. The risk of this outside-in approach is that the health care system
may lose sight of the people and communities for which it serves and cares. In
this article, an "inside-out" model for viewing health care in a geriatric
population is presented from the perspective of patients and providers, placing
the provider in a proactive rather than reactive role. By focusing attention on
the outcomes or value a patient is experiencing, providers are challenged to
consider new ways of managing care.
PMID- 10181842
TI - The population of people age 80 and older: a sentinel group for understanding the
future of health care in the United States.
AB - Those age 80 years or older (80+) constitute a relatively small percentage of a
health care system's population. However, because of the associated risks, costs,
and variation of their medical care, 80+ patients are sentinel for elder care
quality. This article describes the survey components of the 80+ Project. This
project was designed to help clinicians gain a complete picture of the special
needs of the 80+ population. The information about these patients' health and
functional status, how they utilize health care resources, how they obtain access
to care, and their satisfaction with the care is useful for clinicians who wish
to improve health care delivery.
PMID- 10181844
TI - An easy way to measure quality of physician-patient interactions.
AB - This article describes a simple method for rating the patient-clinician
interaction from the perspective of the older adult patient, with the goal of
improving patient outcomes. A measure for rating the quality of an interaction
with a patient who is bothered by a problem is called the Functional Education
Index or FNXEI. Usually, sicker patients are known to be less satisfied with
their medical care. What is unique about the FNXEI is that it is not affected by
a patient's overall health, giving clinicians an accurate account of their
interactions with patients. Considering this, the FNXEI becomes a useful tool for
improving care because it has face validity and specificity about the type of
care clinicians are providing for their older adult patients.
PMID- 10181843
TI - Assessing access as a first step toward improving the quality of care for very
old adults.
AB - Understanding the barriers to obtaining care that the population of people age 80
and older (80+) experiences is one of the first steps toward developing
organizational and clinical strategies aimed at improving care. This article
reviews the data from the 80+ Project's survey to assess the prevalence of
barriers to care and identify the characteristics that place the 80+ population
at risk. Barriers to access for older adults occur on many levels. Ultimately,
the ability to improve health outcomes through reducing barriers to care is
dependent on the effectiveness and quality of care received. By recognizing the
barriers to care that limit access, health care professionals can begin to
develop strategies to eliminate these barriers and improve the health care of
older adult patients.
PMID- 10181845
TI - End-of-life care for persons age 80 years or older.
AB - At age 80, about 4 of every ten 10 men and 3 of every 10 women will die within 5
years. What should the very old expect of the dying experience? National data
reveal that very old adults experience considerable variation in the use of the
hospital during their last 6 months of life. Physicians report these patients
most often need assistance with self-care, emotional support, nutrition, and pain
control. In order to minimize unnecessary and expensive hospitalization and
improve home management, specific terminal care guidelines are proposed and
illustrated.
PMID- 10181846
TI - Geriatric education: a system approach.
AB - This article describes an institutionwide geriatric educational initiative
(called Geriatrics Awareness Month) that provided didactic and formal
experiential learning designed for health professionals. From an educational
perspective, to learn geriatrics requires systems thinking, and, to learn systems
thinking, geriatrics provides an excellent clinical context. The authors
evaluated the didactic and experiential aspects of Geriatric Awareness Month. For
attendees of didactic sessions, the availability of pocket-sized educational
materials was deemed most valuable. Despite busy schedules, house staff were able
to make a change in their practice and study the effect of this change.
PMID- 10181847
TI - Improving patient care in a changing environment: a teaching case.
AB - In previous articles in this issue, other authors have detailed many issues
regarding how to improve care for a geriatric population. However, those analyses
were done based on survey data that are often difficult to translate into the
setting of an actual practice. This article presents a case study of Bob Collins,
MD, a practicing geriatrician whose life is altered dramatically as external
pressures from the health care system force him to make changes in his practice.
It concludes with an analysis of how Dr. Collins could improve his practice life
and the care he delivers by considering the perspectives of his patients, his
coworkers, and his organization.
PMID- 10181848
TI - Implementing a strategy for improving care: lessons from studying those age 80
and older in a health system.
AB - This article describes some potential solutions to the many practical barriers
that arise when trying to improve clinical care in everyday practice. A useful
mnemonic for incorporating measurement into daily work is called GAPS--setting
Goals, Assessing the current processes, Planning a new approach, and Starting it.
The 80+ Project represents a foundation of information and offers promise to
create durable, productive interactions for elderly individuals and their health
care providers.
PMID- 10181849
TI - Accounting for the move to ambulatory patient groups.
AB - This article focuses on the cost accounting challenge an ambulatory patient group
(APG)-like-based prospective payment system presents to providers and the issues
associated with that challenge. In particular, how can costs be identified, how
can the differences in costs be associated with alternative settings, and how do
costs identified through a detailed resource costing methodology compare to
estimates using alternative measures? The results presented suggest that
decisions made based on current measures of ambulatory cost (i.e., charge-based
measures) need to be reexamined. These decisions could include which services to
provide, what setting is appropriate, and where marketshare opportunities exist.
PMID- 10181850
TI - Physicians and the Universal Declaration of Human Rights.
PMID- 10181851
TI - A treatment denial backfires--with a bang.
PMID- 10181852
TI - The 120 best financial advisers for doctors.
PMID- 10181853
TI - Managed care worries patients--maybe because it confuses them.
PMID- 10181854
TI - Unjustly indicted: a doctor stands trial for murder.
PMID- 10181855
TI - "Show us the money!" How to make sure your fees are collected.
PMID- 10181856
TI - Never count on a managed-care bonus--even though you've earned one.
PMID- 10181857
TI - CDC proposes new surgical site infection guidelines.
PMID- 10181858
TI - Surgery center payment plan is based on APCs (ambulatory patient classification
system).
PMID- 10181859
TI - Highlights of CDC's proposed guidelines.
PMID- 10181860
TI - How do you document competency?
PMID- 10181861
TI - Directors seek common definitions.
PMID- 10181862
TI - Options for identifying instruments.
PMID- 10181863
TI - Surgery by the numbers.
PMID- 10181864
TI - Year 2000 bugs lurking in the OR?
PMID- 10181865
TI - Campaign to end wrong-site surgery.
PMID- 10181866
TI - Computer-aided methods help cancer diagnoses.
PMID- 10181867
TI - New detectors boost mammographic accuracy.
PMID- 10181868
TI - Real-time telediagnosis offers 24-hour service.
PMID- 10181869
TI - Ultrasound facility tests remote video monitoring.
PMID- 10181870
TI - Sharing patient data improves medical care.
PMID- 10181871
TI - DR: the final link to the digital department.
PMID- 10181872
TI - Diagnostic value of an automatic hematology analyzer in patients with hematologic
disorders.
AB - The Sysmex SE-9000 is a newly designed automatic hematology analyzer that
provides complete blood counts and white-cell differential counts. Few reports in
the literature, however, discuss the sensitivity and specificity of this type of
automatic analyzer, especially in patients with hematologic illnesses. This study
compared differences between hematologist assessments and measurements made by
the SE-9000 analyzer of differential counts, immature granulocytes, atypical
lymphocytes, nucleated red cells, and platelet counts. Significant differences
were found between manual and apparatus counting of neutrophils, lymphocytes, and
monocytes but not of eosinophils and basophils. Atypical lymphocytes and
nucleated red cell could not be counted accurately, and when platelet counts fell
below 20 x 10(9)/L, accurate assessments were not possible. We conclude that not
even the Sysmex SE-9000 can provide unflawed results and any suspicious blood
report should be rechecked by an experienced hematologist.
PMID- 10181873
TI - Spinal disc rehabilitation: a new technology.
AB - Low back pain and "computer neck" are frequent complaints during visits to a
physician. Back and neck pain affects up to 60% of all employees at some time in
their careers and is personally and financially devastating. Repetitive
mechanical stress leads to disc degeneration, loss of disc height, and other
abnormalities. The PT machine, which is controlled and coordinated by onboard
computer and fiberoptic feedback sensors, is the first biorobotic system that
alleviates intradiscal pressure and myospasm.
PMID- 10181874
TI - Robotic solid-phase extraction and GC-MS analysis of THC in blood.
PMID- 10181875
TI - Multidisciplinary laboratory management in an integrated health-care system.
PMID- 10181876
TI - Solid-state electrodes for the clinical laboratory.
PMID- 10181877
TI - Final chapter inked in IHC saga.
PMID- 10181878
TI - Reaching agreement on tumor markers.
PMID- 10181879
TI - Finding the right formula to leverage excess lab capacity.
PMID- 10181881
TI - Reference Information Model for Clinical Laboratories. RILA as laboratory
management toolbox.
PMID- 10181882
TI - Barriers to evidence-based care in nursing: historical legacies and conflicting
cultures.
AB - The British National Health Service (NHS) has witnessed many fundamental changes
over the last decade, one of the most significant of which is the imperative for
health-care professionals to ensure that their clinical practice can be supported
by research evidence. This move from intuition and historical ritual to
scientific justification has not been fully successful in either the medical or
non-medical professions, with the result that a great deal of research has been
sponsored at both the national and local levels to investigate the reasons
underlying the research/practice divide. Within nursing the problem has been
particularly exacerbated by its ideological framework, the culture and tradition
of the profession itself and the recent reforms that were intended to raise its
professional status and autonomy. This paper considers the impact of nursing
traditions and stereotypes and the bureaucratic structures of the NHS on the
introduction of evidence-based nursing care. It is suggested that the essential
nature of nursing, its legacy and philosophy, together with the health service's
hidden agendas, have conspired to keep nursing in a subordinated, quasi
professional role as one means by which the workforce can be controlled. Because
the nursing profession has colluded with this, albeit inadvertently, it now needs
to re-establish its complementary functions, in order to salvage its position and
truly establish nursing as a profession in its own right.
PMID- 10181880
TI - Diagnosing breast disease.
PMID- 10181883
TI - Further flexing? Issues of employment contract flexibility in the UK nursing
workforce.
AB - This paper, based on research commissioned by the Royal College of Nursing
(Buchan, 1995), reports on the changing working patterns and flexibility in the
employment of nursing staff in the National Health Service (NHS) in the UK. It
reviews relevant literature, examines official data and draws information from 12
case study NHS trusts. Flexibility is invariably portrayed as a good thing, and
as a means to a positive end, yet is rarely defined in detail, if at all. The aim
of this paper is to consider flexibility not as a slogan or panacea, but in terms
of the rationales for, and likely effects of, changing patterns of nursing work.
It examines the reasons why NHS employers have been attempting to increase the
flexibility of their nursing workforce.
PMID- 10181884
TI - Hospital response to the implementation of prospective payment.
AB - This research examined the competing effects of regulatory intensity (Prospective
Payment System) and inertial pressure on US hospitals' cost of medical materials,
shifting of services from inpatient to outpatient settings, size of the
administrative component, and use of new technology. Among the expected findings,
regulatory intensity was associated with reduced medical material costs, less new
technology and a greater administrative component. Inertial pressures were
associated with higher medical material costs, more new technology and less
shifting of services from inpatient to outpatient settings. It was concluded that
US hospitals respond to regulatory pressures within the context of strong
inertial forces. The stronger the inertial forces, the less dramatic a hospital's
response to regulatory pressures is likely to be.
PMID- 10181885
TI - Specialty location decisions in the reformed NHS: a case study.
AB - A soft systems approach, largely based on soft systems methodology, was used to
steer a study (completed in 1996) of the National Health Service contracting
process. It led to action research projects on a number of related issues. One
such area that emerged very strongly concerns service rationalization and service
planning, and in particular the location of 'small' specialties. A Trust-based
study involving patient flow modelling demonstrates the form these problems can
take within the internal market and highlights the challenge they make to the
contracting process or the new primary care group based commissioning process if
they are to be resolved in a rational manner.
PMID- 10181886
TI - Management of health system reform: a view of changes within New Zealand.
AB - This paper reports on the context and process of health system reform in New
Zealand. The study is based on interviews conducted with 31 managers from three
Crown Health Enterprises (publicly funded hospital-based health care
organizations). A number of countries with publicly funded health services (e.g.,
UK, Australia and New Zealand) have sought to shift from the traditional
'passive' health management style (using transactional management skills to
balance historically-based expenditure budgets) to 'active' transformational
leadership styles that reflect a stronger 'private sector' orientation (requiring
active management of resources--including a return on 'capital' investment,
identification of costs and returns on 'product lines', 'marketing' a 'product
mix', reducing non-core activities and overhead costs, and a closer relationship
with 'shareholders', suppliers and customers/clients). Evidence of activities and
processes associated with transformational leadership are identified. Success of
the New Zealand health reforms will be determined by the approach the new
managers adopt to improve their organization's performance. Transformational
leadership has been frequently linked to the successful implementation of
significant organizational change in other settings (Kurz et al., 1988; Dunphy
and Stace, 1990) but it is too early to assess whether this is applicable in a
health care context.
PMID- 10181887
TI - Managerialism in the health service: partnership or conflict in a management
development programme.
AB - This paper describes a management development programme in a hospital-based Trust
and the differing responses demonstrated by those taking part. In terms of the
impact of the programme, a picture emerges of differentiation and fragmentation
rather than culture being managed to produce a social glue. Following this,
suggestions are made for successful partnerships in the promotion of managerial
effectiveness through management development to clinical services managers in the
health service.
PMID- 10181888
TI - U.S. Attorneys' Offices investigate outpatient clinical laboratory services.
PMID- 10181889
TI - When a physician is HIV positive. An examination of legal and practical aspects.
PMID- 10181890
TI - Some thoughts on historical accidents.
PMID- 10181891
TI - Healthy power for safer healthcare.
PMID- 10181892
TI - Internet for hospital engineers.
PMID- 10181893
TI - Outsourcing.
PMID- 10181894
TI - Re-structure of the engineering services for an area health service.
PMID- 10181895
TI - Organizational and market determinants of HMOs' performance of preventive
practices.
AB - This study validates the measurements of performance of preventive practices and
identifies organizational and market factors that affect variations in the
preventive care practices of health maintenance organizations (HMOs).
Confirmatory factor analysis was used to assess HMO performance, reflecting the
rates of five preventive practice services. A structural equation model of the
preventive practice performance of HMOs was evaluated. It was discovered that
HMOs that employ more board-certified primary care practitioners have a higher
rate of preventive care practices and that market competition and market forces
do not influence the variation in HMO preventive care practices.
PMID- 10181896
TI - Simplicity is best: the learning experience of Good Shepherd Home.
AB - Quality improvement efforts need not be expensive and can produce positive
results almost immediately if a systemic, comprehensive model is used and if top
level management is truly supportive. The following article presents a case study
of a successful quality improvement process mounted at Good Shepherd Home, a
rehabilitation hospital in Allentown, PA. It discusses the key items of the
systems approach and looks at how the items have been implemented and integrated
and the future of the process.
PMID- 10181897
TI - Using continuous improvement to obtain and document informed consent.
AB - This article describes a continuous improvement team's activities to improve the
process of obtaining and documenting informed consent and to decrease the
incidence of communication errors during the surgical scheduling process.
Integrating surgeons' informed consent process at their office sites with
hospital records was the key to success.
PMID- 10181898
TI - Defining outpatient scopes of practice for allied healthcare practitioners.
AB - The definition of scopes of practice for allied healthcare practitioners in
outpatient settings is an emerging healthcare topic in this era when
technologically advanced procedures are being done and diagnostics, therapies,
and care are being given in outpatient settings. The standards of care and
practice under which allied health professionals provide care must be defined
within an organization in order to provide the high-quality integrated healthcare
that is the benchmark of excellence. One way to increase leadership and staff
awareness is to provide experts in each allied health discipline the opportunity
to define their scopes of practice, as the Joint Commission suggests, based on
the rules and regulations that govern those practices.
PMID- 10181899
TI - Development of the physician satisfaction survey instrument.
AB - Continuous quality improvement (CQI) activities depend on valid and reliable
instruments to generate data. An evaluation of internal and external customer
satisfaction is one of the pillars of the CQI process. This article describes the
development of a valid and reliable instrument for measuring physicians'
satisfaction with the orthopedic nursing units at a major medical trauma center.
The physician satisfaction survey instrument was found to be internally
consistent (alpha = .95). Confirmatory factor analysis revealed that 68% of the
variance in physician satisfaction scores (eigenvalue = 8.14) was explained by
using a single-factor model.
PMID- 10181900
TI - Implementing and evaluating outcome indicators of performance for mental health
agencies.
AB - Regulation-based processes for evaluating the performance of mental health
agencies are gradually changing to focus on measuring the effectiveness of mental
health services in obtaining the best possible outcomes. The decreased
availability of resources for serving people with mental health problems has led
to an emphasis on effectiveness, which is often expressed in terms of
accountability. Thus, a singular reliance on compliance with practice standards
has shifted to the need to be able to demonstrate that funds appropriated for
mental health services are being used in ways that result in valued outcomes. In
Colorado, this shift has led to the development of performance indicators that
provide information reflecting stakeholder values about the performance outcomes
of the mental health system. This article describes these performance indicators
and presents the data that led to a decision to award monetary incentives to two
community agencies. Potential benefits and pitfalls of Colorado's performance
indicator process are also discussed.
PMID- 10181901
TI - Comparative data analysis using collaborative skilled nursing/long-term care
indicator assessment.
AB - This article describes a process developed by Eastern Mercy Health System (EMHS),
headquartered in Radnor, PA, to identify opportunities for quality improvement
using defined outcome-based indicators in skilled nursing and long-term care
(SN/LTC). The model is built on collaboration among the system's freestanding and
hospital-based facilities; it includes a cyclical approach to the exchange of
information. The experiences of three of the system's members reflect how each
has realized measurable benefits by applying to their unique settings the lessons
learned through the collaborative process.
PMID- 10181902
TI - Decreased length of stay for patients with colorectal cancer: implications of DRG
use.
AB - Hospital length of stay (LOS) has declined significantly at Mt. Sinai Hospital
with the advent of diagnosis-related groups (DRGs). Patients with colorectal
cancer who were operated on before and after the implementation of the DRG were
compared to determine whether the shorter LOS reflected changes in the patient
population or changes in the way patients were being treated. Both preoperative
and postoperative LOS declined significantly for DRG patients. The decreased LOS
for DRG patients could not be attributed to a decreased severity of disease
because DRG patients presented with significantly more advanced tumors. The DRG
patients had significantly less operative blood loss; shorter, less extensive
procedures; fewer transfusion; shorter specimen lengths; shorter margins of
resection; and fewer postoperative complications than the pre-DRG patients. Other
measures of disease severity (i.e., admission hematocrit, tumor differentiation,
and tumor size) and patient mix (i.e., age and sex) did not change. These results
suggest that with the use of DRGs, surgeons may have modified certain aspects of
treatment for colorectal cancer in an attempt to shorten LOS.
PMID- 10181903
TI - Finding ways to reduce violence in psychiatric hospitals.
AB - Managers at Kino Community Hospital in Tucson, AZ, were growing concerned about
patient violence and its effects. This worry resulted from an increasing number
of injuries to staff caused by patients in addition to the escalating costs of
workers' compensation claims. Managers theorized that staff injuries could be
decreased by changing staffing patterns, practicing crisis intervention
techniques more frequently, and establishing continuing education classes. The
hospital therefore implemented a step-by-step violence prevention program for its
inpatient psychiatric department, an action that led to markedly fewer staff
injuries by the end of 1996. A detailed account of this program follows.
PMID- 10181904
TI - Does considering severity of illness improve interpretation of patient
satisfaction data?
AB - With the emergence of new, relatively low-cost code-based severity indexes, this
question arises: Do complex descriptions of patient population in terms of
severity yield a clearer picture of patients' opinions about hospital care and
service? Consumers and third-party payers of healthcare are using patient
satisfaction data with increasing frequency to evaluate the quality of care that
hospitals provide. Insurers also use satisfaction data, when they are available,
for contracting and ensuring provider accountability. The study described here
examines whether the all patient refined-diagnosis related groups (APR-DRG)
severity-of-illness rating system, in particular, can explain the variability in
inpatient satisfaction ratings independently of patient demographics and clinical
events. Multiple logistic regression was used on a data set of 3,720 patient
records from one tertiary care facility, and model terms were fitted on the basis
of reason for admission, year, gender, length of stay, age, and severity. The
findings were that age and reason for admission were consistent predictors of
high satisfaction on 14 survey items. APR-DRG severity was not a significant
factor. Length of stay made a small but significant contribution on three items
related to clinical quality.
PMID- 10181905
TI - State contracting initiatives for quality improvement in asthma care.
AB - This article examines the role of a state Medicaid program in standardizing and
implementing quality performance measures for providers. It describes the Asthma
Education and Primary Care Clinician Linkages Quality Improvement Program (QIP),
one aspect of the ongoing Hospital Quality Initiative in Massachusetts. In
October 1996, the second year of the initiative, the Massachusetts Division of
Medical Assistance requested that all contracting hospitals submit quality
improvement process and outcome measures related to asthma care, including
practice guidelines, patient education materials, and documentation mechanisms to
facilitate patients' appropriate follow-up contact with primary care clinicians.
A team of evaluators reviewed these materials to determine whether hospitals had
baseline data in place for asthma QIP development. Information forums were held
with three reviewers and the hospitals to discuss various programs and progress
toward quality improvement in asthma care. Reviewers also worked to identify
hospital programs that could be used as models and those that would benefit from
assistance in meeting the state's program goals.
PMID- 10181906
TI - Exploring the Internet--what a novice needs to know.
PMID- 10181907
TI - The component alignment model: a new approach to health care information
technology strategic planning.
AB - The evolving health care environment demands that health care organizations fully
utilize information technologies (ITs). The effective deployment of IT requires
the development and implementation of a comprehensive IT strategic plan. A number
of approaches to health care IT strategic planning exist, but they are outdated
or incomplete. The component alignment model (CAM) introduced here recognizes the
complexity of today's health care environment, emphasizing continuous assessment
and realignment of seven basic components: external environment, emerging ITs,
organizational infrastructure, mission, IT infrastructure, business strategy, and
IT strategy. The article provides a framework by which health care organizations
can develop an effective IT strategic planning process.
PMID- 10181908
TI - Implementing enterprisewide databases: a challenge that can be overcome.
AB - The evolving health care industry is placing new demands on its participants.
Traditional institutional boundaries are being replaced by the need to cooperate,
collaborate, and share increasingly scarce resources to provide high-quality care
to patients. Information, which historically was coveted and protected, must now
be shared by the multiple providers and organizations that together provide
services. This need to share information has brought on the need for
organizations to build common databases from which reports can be run, trends can
be noted, and patient information can be drawn. Data warehouses and clinical data
repositories are being recognized as solutions to issues of segregation of
information. Both solutions are relatively new to health care, and there is
acknowledgment that neither is simple to implement and that both represent new
challenges to health care organizations. The article provides working definitions
of the two solutions, describes at a high level some of the challenges associated
with their implementation, and provides some of the key steps required to
develop, implement, and realize the benefits of the clinical data repository or
data warehouse.
PMID- 10181909
TI - Designing health care information systems for integrated delivery systems: where
we are and where we need to be.
AB - A critical step in evolving an integrated delivery system (IDS) is planning,
designing, and technologically realizing an efficient, appropriate, and effective
infrastructure for developing an integrated network of information systems. The
key to meeting this objective philosophically, logically, and physically in the
face of rapid advances in computing technology and communication trends is often
poorly understood by health providers and managers. The article discusses the
concept of a total quality management information system model and illustrates
how this sort of thinking can be applied to guide the critical steps that must be
undertaken to plan, design, and develop a networked infrastructure of health care
information systems that can facilitate information exchange and sharing among
multiple health care providers within an IDS.
PMID- 10181910
TI - Deploying a new model for clinical information delivery.
AB - Information is a dynamic, potentially high-value resource that institutions can
use to achieve superior performance. The myriad of advanced information
technology projects, however, delivers to the institution's clinical and business
processes unpredictable deluges of information objects, both paper and
electronic, that may add little value to the processes. Also, because the
information arrival is often a trigger for work steps, its illogical arrival may
actually dilute productivity and quality. The article describes an information
distribution engine in use at a large hospital in the southwestern United States
that allows remotely located recipients to define individualized rules for
controlling the subset of diverse information that they receive, select its
transmission and display media, and choreograph the sequence and timing of its
arrival at their desktops.
PMID- 10181911
TI - Cost-volume-profit and net present value analysis of health information systems.
AB - The adoption of any information system should be justified by an economic
analysis demonstrating that its projected benefits outweigh its projected costs.
Analysis differ, however, on which methods to employ for such a justification.
Accountants prefer cost-volume-profit analysis, and economists prefer net present
value analysis. The article explains the strengths and weaknesses of each method
and shows how they can be used together so that well-informed investments in
information systems can be made.
PMID- 10181912
TI - Object-oriented analysis and design: a methodology for modeling the computer
based patient record.
AB - The article highlights the importance of an object-oriented analysis and design
(OOAD) methodology for the computer-based patient record (CPR) in the military
environment. Many OOAD methodologies do not adequately scale up, allow for
efficient reuse of their products, or accommodate legacy systems. A methodology
that addresses these issues is formulated and used to demonstrate its
applicability in a large-scale health care service system. During a period of 6
months, a team of object modelers and domain experts formulated an OOAD
methodology tailored to the Department of Defense Military Health System and used
it to produce components of an object model for simple order processing. This
methodology and the lessons learned during its implementation are described. This
approach is necessary to achieve broad interoperability among heterogeneous
automated information systems.
PMID- 10181913
TI - Building a successful enterprise master patient index: a case study.
AB - To ensure success in building an enterprise master patient index (MPI), an
understanding of the complexities of the internal duplicate files and the overlap
population is essential. Merging multiple MPIs is complicated and requires time
and a commitment to accuracy. Most organizations underestimate the importance of
the following ground rules for building an enterprise MPI: Internal duplicates
need to be corrected; linking patient files with a statistical weighting
algorithm is far superior to using rigid criteria; there are more overlap patient
files than an organization usually perceives; an imprecise and incomplete base of
demographic data will multiply the error rate for the enterprise; preliminary
data analysis is critical to avoid linkage problems during conversion; and
accurate data collection and monitoring are imperative for ongoing data
integrity. The article discusses the major steps involved in creating an
enterprise MPI and recommends solutions to common problems encountered during
conversion.
PMID- 10181914
TI - The challenge of integrating clinical information systems in an integrated
delivery system.
AB - The development and implementation of the information systems necessary to
support an effective and efficient continuum of care and to measure the quality
and cost of that care present complex information systems integration challenges.
The article discusses the integration challenges and concludes with a review of
strategies that an integrated delivery system can adopt to begin to address them.
PMID- 10181915
TI - Shining a light on abuse.
PMID- 10181916
TI - Killer bacteria/E. coli O157:H7. Anatomy of an outbreak.
PMID- 10181917
TI - Going out on a limb. Louisville doctors announce the first "successful" hand
transplant before they even lift a scalpel.
PMID- 10181918
TI - Prevent crib death.
PMID- 10181919
TI - The effect of a rapid sequence induction protocol on intubation success rate in
an air medical program.
AB - The purpose of this study was to examine the percentage of successful intubations
before and after implementation of a rapid sequence induction (RSI) protocol in
patients treated by our flight nurses and paramedics. The records of 100
intubation attempts before the RSI protocol was implemented and 98 after
implementation were reviewed. Success rate of intubation was 79% in the preRSI
patient group and 84.7% in the postRSI group. No significant difference existed
in the number of patients successfully intubated preRSI compared with postRSI.
The statistically significant patient characteristics associated with
unsuccessful intubation were facial trauma, combativeness, vomiting, and nasal
bleeding.
PMID- 10181920
TI - Blood usage in rotor-wing transport.
AB - INTRODUCTION: Blood transfusion for hemorrhagic shock is standard therapy. The
purpose of this study was to document the development of protocols for
administering red blood cells and review the experience with inflight blood
transfusions. SETTING: This study was conducted at a hospital-based rotor-wing
(RW) program whose service area is a large rural area in southeastern Minnesota.
A BK 117 with a flight nurse/flight nurse configuration was used. METHODS: The RW
registry was accessed during a 3-year period (August 1993 to July 1996), and 2131
records were reviewed to retrospectively analyze blood use during transport.
Blood bank records and protocols also were reviewed. RESULTS: This helicopter
program maintains a refrigerator with 4 units of O-negative blood that is kept in
the hangar and serviced by the blood bank. Blood was taken on all appropriate
transports (91% interfacility, 9% scene), and 94 of 2131 patients (4%) were
transfused. Criteria for blood transfusion included Hgb < 10, persistent
hypotension after resuscitation, and clinical signs of shock. Medical conditions
consisted of trauma (48% of patients), gastrointestinal (GI) bleed (25%),
abdominal aortic aneurysm (AAA) (17%), and other (10%). The mean Hgb before and
after transport was 8.9 and 10.2, respectively; 38% of the patients received an
average of 3 units before transport. Overall, 2 units red blood cells were given
in flight and another 12 units during hospitalization. No complications occurred
with blood transfusions. CONCLUSIONS: Selected RW patients will benefit from in
flight blood transfusions. Proximity of blood storage to the helicopter is
mandatory to avoid delays in transport. A close working relationship with blood
bank personnel ensures ready availability of current O-negative blood.
PMID- 10181921
TI - Blood transfusion and acute intravascular volume loss.
PMID- 10181922
TI - Blood transfusions--closing the loop.
PMID- 10181923
TI - High performance team interaction in an air medical program.
AB - INTRODUCTION: The purpose of this qualitative study was to identify and describe
the elements of a high performance team interaction on an air medical transport
mission. METHODS: The phenomenologic method as described by Giorgi was used to
guide data collection and analysis. Six flight nurses from around the United
States were interviewed and audiotaped as they described their subjective
perception of a high performance team experience. RESULTS: Four themes emerged
from the data: collaboration, mutual respect and trust, fitness standards, and
synergy. CONCLUSION: Implications for flight crews involved in this high
performance environment may require attention to the identified themes to promote
team performance.
PMID- 10181924
TI - Basics of research (Part 13): Qualitative research--an example.
PMID- 10181925
TI - Business principles for air medical professionals. Part 2: Basic business
structure.
PMID- 10181926
TI - Aggressive out-of-hospital treatment regimen for severe closed head injury in
patients undergoing air medical transport.
AB - The impact of aggressive out-of-hospital management on disposition for 1286
patients with closed head injuries in ground advanced life support (ALS) and
helicopter services was evaluated over 60 months in San Diego County. The case
group included 196 air medical patients with a scene Glascow coma scale (GCS) < 9
who were treated according to a standard head injury protocol. The frequency
matched control group included 1090 ground ALS patients receiving airway
management with hyperventilation but neither induction agents nor mannitol. The
trauma registry provided admission and discharge dates, neurosurgical
interventions, and disposition. Patient age, scene GCS, head and neck abbreviated
injury scale (HNAIS), and injury severity score (ISS) served to stratify study
groups. Case-control distribution of mortality was compared with the two-tailed
Mantel-Haenszel weighted odds ratio (OR) and chisquared test; significance at P <
or = 0.05. The case group displayed an 11% decreased mortality (P < 0.01),
remaining significant after adjusting for age (P = 0.05) and scene GCS (P =
0.06). The case group displayed 10% (P < 0.01) greater survivor discharges to
rehabilitation and 6% (P < 0.05) fewer discharges to extended care facilities.
This study's data indicate a strong possibility for improved patient morbidity
and mortality in severe closed head injuries treated with an aggressive treatment
protocol and rapid air medical transport.
PMID- 10181927
TI - Managed care pressure cooks up a bill.
PMID- 10181928
TI - Helping employees get a grip.
PMID- 10181929
TI - Finding time, stopping the frenzy.
AB - While the deleterious consequences of long hours of work for individuals,
families and communities have previously been documented, the assumption that
long hours are necessary to get the work done, especially in a world where speed
is becoming increasingly critical to corporate success, has prompted little
challenge. So Leslie Perlow, an assistant professor of business at the University
of Michigan, Ann Arbor, set out to explore the necessity for the seemingly
endless workdays that so many postindustrial settings require. Her study of a
group of software engineers at a Fortune 500 company--identified only as the
Ditto Corp--is detailed in her book, Finding Time: How Corporations, Individuals,
and Families Can Benefit from New Work Practices (Cornell University Press,
1997). Perlow's research reveals a "sad and all too common tale" of workers
harried by competing demands, frequent interruptions and shifting deadlines. To
meet the firm's expectations, the engineers she studied sacrificed home life,
focused on individual tasks to the detriment of group goals and, in many cases,
eventually lost any enthusiasm they'd had for working for the company. There has
been some recognition that stress and burnout may be bad for a corporation as
employees become less committed, decide to leave or get fired and that this kind
of turnover can hurt the firm in the longer term. But Perlow documented the
additional, and quite significant, shorter-term costs to the corporation of the
current way of using time at work. What she found was a "vicious time cycle:"
Time pressures led to a crisis mentality, which led to "individual heroics." That
is, I'll do whatever it takes to do my job--even if it means interrupting you
while you try to do yours. For the engineers Perlow studied, the lack of helping,
the constant interruptions and the perpetual crises--clearly illustrated by the
daily log that appears on page 34--made it harder to develop products.
Ultimately, they worked long hours to complete tasks they'd been too busy to do
earlier because of the constant interruptions. Worse, because everyone was busy
responding to crises, no one had time to prevent future crises, thus perpetuating
the cycle. But as dire as the situation sometimes seemed, change was possible.
The "quiet time" phase of the author's nine-month study indicated that
productivity could be enhanced by structuring work time to allow the engineers
intervals to work alone, uninterrupted. After this first phase, about two out of
three of the 17 people involved said their productivity during quiet time was
above average. Nearly as many said overall productivity was above average as
well. This implies that the costs of the current way of using time exceed the
benefits. The data further show that change must be collective, addressing all
elements of the vicious cycle. The promising implication is that collective
change could benefit everyone--corporations, individuals and families. The work
process could be made more efficient and effective. At the same time, individuals
could succeed at work and still have time for responsibilities outside of work;
people might not have to choose so definitively between their work and their home
lives. To make the necessary changes, however, will require a shift from a system
that rewards individuals heroics and long hours to one that rewards individuals'
contributions to their teams--without the accompanying emphasis on visible work
hours. That is, there must be a shift in emphasis from individual to collective
achievement. And there must be a sharing of the resulting gains in efficiency
between employees and employers. In the following excerpt from her book, Perlow
describes what is needed to turn a vicious time cycle into a "virtuous" one:
PMID- 10181930
TI - Stalking a silent killer.
PMID- 10181932
TI - Behavioral health: don't ignore, integrate.
PMID- 10181931
TI - Defogging Medicare reform.
PMID- 10181933
TI - Head to head. Should employer-based coverage end? Discussion.
PMID- 10181934
TI - Data watch. Small biz will pay to protect consumers.
PMID- 10181935
TI - Compensation monitor. Health care systems turn to bonus pay.
PMID- 10181936
TI - Employers tell health plans 'not so fast' on premium hikes.
PMID- 10181937
TI - Missing the mark.
PMID- 10181938
TI - Making the Medicare/managed care marriage work.
PMID- 10181939
TI - A conversation with David Lansky, Ph.D.
PMID- 10181940
TI - Understand guiding principles when mixing business, medicine.
PMID- 10181941
TI - Remuneration arrangements important part of Stark II regulations.
PMID- 10181942
TI - Managed care outlook. What HMOs, insurers review when predicting health care
costs.
PMID- 10181943
TI - IDS growth fuels I.T. spending, but confuses issues.
PMID- 10181944
TI - Blues Association calls for HIPAA to apply to employers.
PMID- 10181945
TI - E-mail helps practice improve its efficiency.
PMID- 10181946
TI - Safe and secure. Interview by Bill Siwicki.
PMID- 10181947
TI - Provider automation. Taking care of business.
PMID- 10181948
TI - The amazing new powers of the CIO.
AB - CIOs, who used to focus on back-office information systems, are getting more
involved in executive-level strategic planning, clinical systems implementation
and new technology evangelism. With so much going on, the CIO's role is becoming
increasingly difficult. Many CIOs have been able to take practical steps to meet
their changing--and expanding--job requirements.
PMID- 10181949
TI - Disease management hits home.
AB - Patients suffering from chronic illnesses, such as diabetes, asthma, congestive
heart failure and cancer, are beginning to find significant value in technologies
designed to help them take care of themselves at home. And providers and payers
are finding that new home care information technologies are helping to curb
costs.
PMID- 10181950
TI - Intranets emerging as new human resources platform.
AB - Some pioneering health care organizations are taking the innovative step of
capitalizing on their intranets, private networks that use Internet technologies
and protocols, for human resources purposes. These providers and payers plan to
use their intranets to enable employees to enroll a new family member in a
benefit plan or check how many vacations days they have left.
PMID- 10181951
TI - Software helps providers hit the correct billing codes.
AB - Faced with the prospect of being slapped with fines for filing fraudulent
Medicare and Medicaid claims if they don't follow regulations to the letter, some
health care providers are relying on coding software. These systems help them
stay in compliance with federal regulations as well as the requirements of other
payers. The government's zeal to crack down on coding compliance combined with
the complexity of coding regulations is leading more health care organizations to
turn to automation.
PMID- 10181952
TI - Building a vocabulary. A new, improved version of SNOMED has the potential to
ease the collection and analysis of clinical data.
PMID- 10181953
TI - Corporate strategy. No longer the quiet company. Epic Systems Corp.
PMID- 10181954
TI - Data security. Raising the drawbridge.
PMID- 10181956
TI - Seniors' demographic revolution redefines health care marketing, financing, and
delivery.
PMID- 10181955
TI - Managed care. Automating the sales game.
PMID- 10181957
TI - Choices in death and dying: "heroic" high-tech medicine vs. low-cost
alternatives.
PMID- 10181958
TI - Medicare reform will reshape senior health market.
PMID- 10181959
TI - Avoid hiring the wrong clinicians: ask in-depth interview questions, spot red
flags.
PMID- 10181960
TI - Watch for legal risks when hiring.
PMID- 10181961
TI - Improving relationships with difficult consultants.
PMID- 10181962
TI - Cordless phones take charge in the ED.
PMID- 10181963
TI - Ravenswood incident prompts hard look at policies: know responsibilities for
patients outside the ED.
PMID- 10181964
TI - Convince your administrator to invest in EMS.
PMID- 10181965
TI - Hire an EMS coordinator.
PMID- 10181966
TI - New Orleans ED saves $200,000 each year with electronic charting.
PMID- 10181967
TI - Long-term contracts: hope behind the hype?
PMID- 10181968
TI - Crozer-Keystone rethinks its physician incentives.
PMID- 10181969
TI - Who's been good and who's been really good? The Sachs Group says.
PMID- 10181970
TI - Will medical intranets smooth the rocky road to the future? Panel discussion.
PMID- 10181971
TI - Providers disappointed in decision on deemed status; reaction to proposed new
enforcement initiatives mixed.
PMID- 10181972
TI - Industry groups seek relief from PPS burden, submit comments to HCFA on interim
final rule.
PMID- 10181973
TI - Critical pathways can help providers cut costs, improve care.
PMID- 10181974
TI - Summaries of the OIG's 1997 advisory opinions.
PMID- 10181975
TI - Advisory opinion No. 98-4: what's next?
PMID- 10181976
TI - JCAHO Sentinel Event Policy still unsettled.
PMID- 10181977
TI - The asymptomatic ill and genetic discrimination.
PMID- 10181978
TI - U.S. Department of Labor enters the fray of health care consumer protection.
PMID- 10181979
TI - OIG advises that marketing/distribution arrangement may violate anti-kickback
provision.
PMID- 10181980
TI - Independent diagnostic testing facilities (IDTF): a new Medicare provider entity.
PMID- 10181981
TI - Physician incentive plan rules--application to IPAs and intermediate
organizations.
PMID- 10181982
TI - Evaluation and management guidelines: curse or cure?
PMID- 10181983
TI - Advisory opinion No. 98-4: why is anyone surprised?
PMID- 10181984
TI - Rev. Rul. 98-15: what does it mean for joint ventures between nonprofits and for
profits.
PMID- 10181985
TI - Basic primer on federal fraud and abuse statutes.
PMID- 10181986
TI - PACS: a focus on information delivery.
PMID- 10181987
TI - The power of ultrasound.
PMID- 10181988
TI - Assessing equipment repair and asset management.
AB - As reimbursement continues to decline, healthcare managers are now forced to seek
out and establish alternative means for ensuring optimal patient care delivery
via maximized equipment uptimes, minimized downtimes, increased productivity and
decreased expenses. And, while our benchmarking survey documented manufacturers'
service contracts as the "best practice" for repair of equipment in radiation
oncology, this method was also identified as the most costly. As a result,
serious consideration must be given to alternate methods, irrespective of
advantages and disadvantages. As a new industry-wide product, asset management is
still another viable method and alternative for consideration with regard to
equipment maintenance and repair.
PMID- 10181989
TI - Steps.
PMID- 10181990
TI - The cost-effectiveness of treatment with lamivudine and zidovudine compared with
zidovudine alone: a comparison of Markov model and trial data estimates.
AB - In this paper, we present a Markov model for estimating the cost-effectiveness of
combination therapy with lamivudine (LMV) and zidovudine (ZDV) compared with ZDV
alone. We also compare the predictions of the Markov model for the impact of
combination therapy on trial period costs with the actual impact of combination
therapy on selected trial period costs estimated from data collected during the
clinical trials. In the Markov model, disease stages were defined by CD4 cell
count. Based on clinical trial data for patients with CD4 counts higher than 100
cells/mm3, the model assumed that the CD4 cell count level could be maintained
above the level at the initiation of therapy for 6.5 months with monotherapy and
for 18 months with combination therapy. After this period, transition rates for
natural disease progression were used. Incremental lifetime costs and quality
adjusted life years gained with LMV/ZDV compared with ZDV alone were estimated
for cohorts of patients initiating antiretroviral therapy at four different CD4
cell count stages. Cost per life year gained varied from $10,000 to $18,000, and
cost per quality-adjusted life year gained varied from $14,000 to $27,000. In
both cases, the combination therapy was more cost-effective when started earlier
in disease progression. These estimates were not sensitive to changes in key
parameter values. In addition, the model was used to estimate the impact of
combination therapy on healthcare costs during the trial period; these estimated
costs were compared with data on the cost of resource use collected during the
clinical trial for hospital stays, unscheduled visits, medications, and
outpatient procedures. Both the Markov model estimates and the trial data
estimates for the trial period showed cost savings in other medical costs, though
these were not large enough to completely offset the increased cost for
antiretroviral therapy. The model estimates were more conservative than the
estimates based on the trial data.
PMID- 10181991
TI - Introducing managed care to the medical school curriculum: effect on student
attitudes.
AB - In order to assess the effect of clinical training and didactic instruction on
medical student attitudes toward managed care, we conducted a survey of all
medical students at the midpoint of their third year clerkships at the University
of Massachusetts Medical School. The students were exposed to clinical training
in managed care settings and a 2-day required course on the principles underlying
managed care. The main outcome measures were student attitudes toward the
concepts of managed care, managed care organizations, and future careers in
managed care. Students also assessed the attitudes of medical faculty toward
managed care. Attitudes of students with previous clinical training in managed
care settings did not differ from those of students without such exposure toward
the concepts underlying managed care or managed care organizations and were less
positive about careers in managed care. Student responses before and after the 2
day course on managed care demonstrated that attitudes moved in a significantly
positive direction. Seventy-one percent of students reported that the opinions
they had heard from medical faculty about managed care were negative. Preparing
medical students to practice medicine effectively in managed care settings will
require focused attention on managed care issues in the medical school curriculum
and the combined efforts of academic health centers and managed care
organizations.
PMID- 10181992
TI - A new method of developing expert consensus practice guidelines.
AB - To improve the quality of medical care while reducing costs, it is necessary to
standardize best practice habits at the most crucial clinical decision points.
Because many pertinent questions encountered in everyday practice are not well
answered by the available research, expert consensus is a valuable bridge between
clinical research and clinical practice. Previous methods of developing expert
consensus have been limited by their relative lack of quantification,
specificity, representativeness, and implementation. This article describes a new
method of developing, documenting, and disseminating expert consensus guidelines
that meets these concerns. This method has already been applied to four disorders
in psychiatry and could be equally useful for other medical conditions. Leading
clinical researchers studying a given disorder complete a survey soliciting their
opinions on its most important disease management questions that are not covered
well by definitive research. The survey response rates among the experts for the
four different psychiatric disorders have each exceeded 85%. The views of the
clinical researchers are validated by surveying separately a large group of
practicing clinicians to ensure that the guideline recommendations are widely
generalizable. All of the suggestions made in the guideline are derived from, and
referenced to, the experts' survey responses using criteria that were established
a priori for defining first-, second-, and third-line choices. Analysis of survey
results suggests that this method of quantifying expert responses achieves a high
level of reliability and reproducibility. This survey method is probably the best
available means for standardizing practice for decisions points not well covered
by research.
PMID- 10181993
TI - Patient consultation in a managed care setting: guiding pharmacy into the future.
AB - Managed care organizations are excellent environments for pharmaceutical care
programs to demonstrate their impact on patient care outcomes and to decrease
costs. Patient consultation is the cornerstone in implementing pharmaceutical
care because it increases patient contact with the pharmacists while improving
patient compliance with drug therapy (adherence). Implementation of a patient
consultation program that verifies patients' understanding of their disease and
therapy gives the pharmacist information necessary to monitor drug therapy. Use
of strategic planning to overcome barriers, followed by the development of local
standards of practice, will refocus the practice philosophy to one of improving
patient outcomes. Pharmacy managers must demonstrate and document the value that
patient consultation brings to the patient and the healthcare system. Then, they
must integrate their counseling effort with other health education efforts of the
managed care system. Pharmacists will gain the support of other disciplines by
reinforcing their efforts. Together they can work to decrease the problems that
are inherent with drug therapy. These goals can be accomplished with minimal
expense and have the potential to produce significant savings in healthcare
costs.
PMID- 10181994
TI - Should clinicians rely on expert opinion or empirical findings?
PMID- 10181995
TI - Compliance with antihypertensive therapy: raising the bar of expectations.
AB - Recent advances in the effectiveness of antihypertensive therapies and the
measurement of medication-taking behavior have raised the bar of expectations,
both for patients and prescribing clinicians. This article reviews the principal
findings and makes recommendations to improve pill taking among patients with
hypertension. It summarizes several studies related to hypertension epidemiology,
component behaviors contributing to suboptimal compliance with prescribed
antihypertensive medications, the direct and indirect costs of nonadherent
behaviors, and measures of pill-taking behavior. Based on this analysis, current
levels of hypertension detection, treatment, and control remain suboptimal.
Heuristics for adjusting antihypertensive regimens may be misleading and too
simplistic. More than half of those patients failing to achieve goal blood
pressure display suboptimal compliance rather than an inadequate regimen. In
conclusion, there is a need for enhanced sophistication about medication-taking
behavior, especially for hypertension, so that more patients with this condition
can fully benefit from effective treatments.
PMID- 10181996
TI - In vitro and skin testing for allergy: comparable clinical utility and costs.
AB - Controversy exists concerning the appropriate use of skin testing and in vitro
testing for the diagnosis of allergy, particularly inhalant allergy. Earlier
comparisons of skin testing and in vitro testing concluded that skin testing had
superior accuracy at lower expense. In light of new developments with in vitro
allergy testing, however, this issue should be reconsidered. A review of the
recent scientific literature indicates that in vitro and skin testing are highly
correlated. However, without the existence of an independent gold standard for
inhalant allergy, it is not possible to determine which test is more accurate.
The accuracy of either test can be compromised if conducted using different
protocols or having insufficient quality control. Given their respective
trajectories for technological advancement, quantification, and quality control,
in vitro testing may offer the more standardized approach. Although the cost per
test of in vitro testing remains greater than that of skin testing, the per
patient costs of the two modalities appear to be comparable, given the greater
number of allergens typically used in skin testing. In summary, both skin testing
and in vitro testing are acceptable as frontline diagnostic tools.
PMID- 10181997
TI - Impact of pharmacist consultations provided to patients with diabetes on
healthcare costs in a health maintenance organization.
AB - We conducted a study to assess the impact on healthcare utilization and costs of
pharmacist consultations provided to patients with diabetes. Data for this study
were derived from a larger study conducted by Kaiser Permanente and the
University of Southern California that evaluated three alternative models of
pharmacist consultations (control, state, and Kaiser). Computerized data were
available for patient demographic characteristics and healthcare utilization. We
used medication data to classify patient cohorts as insulin only or oral
antidiabetics +/- insulin. We estimated hospitalization costs based on diagnostic
related group and medication costs based on average wholesale price; office
visits were estimated at $70 each. In the insulin only cohort, total costs for
patients who had their prescriptions filled at a state model pharmacy were 7.8%
less than those for patients filling prescriptions at a control model pharmacy (P
= 0.008). In the oral +/- insulin cohort, total costs for patients filling new
prescriptions at a Kaiser model pharmacy were 21.9% less than those for patients
using a control model pharmacy (P = 0.0001). The state model also was negatively
correlated (beta coefficient, -0.0997) with total costs (P = 0.0001). These data
suggest that pharmacist consultations provided to patients with diabetes can
decrease total healthcare costs in a health maintenance organization.
PMID- 10181998
TI - Disease management programs: benchmarking costs, savings, ROI.
AB - Consumer and employer demands, financial pressures, and accreditation
requirements have propelled disease management into its own fledgling industry,
but there is still no one-stop shop for information, at least not for free.
Experts suggest using a disease management vendor's guaranteed savings, not the
fee per patient, as a benchmark. Middle- to high-priced vendors are generally the
most cost-effective. Factors that affect costs include your patient mix, the
amount of risk you want the vendor to assume, and how many bells and whistles you
want in your program.
PMID- 10181999
TI - Is it better to build or buy disease management?
PMID- 10182000
TI - Need a diabetes program? Database can help prove it.
AB - A new database from the Evanston, IL-based consulting firm Sachs Group contains
extensive diabetes prevalence and utilization statistics right down to the county
and zip code level. Sachs says relying on national statistics instead of local
ones could severely skew your benchmarking efforts. Local numbers can offer
realistic expectations of patient days and emergency room visits, for instance,
to help you set goals and rates for your program.
PMID- 10182001
TI - Can JCAHO, NCQA, AMAP pull joint effort off?
PMID- 10182002
TI - Hospitals deliver reduced cesarean rates.
AB - The U.S. cesarean rate remains at about 22% of babies, but national goals say the
rate should be more like 15%. A collaborative group of hospitals worked
intensively for nine months to reduce rates by 25%. Issues addressed included
managing pain more effectively, educating pregnant women, and avoiding admissions
for false labor.
PMID- 10182003
TI - Aggressive HIV treatment cost-effective.
AB - Early treatment preserves immune function and may lower the probability that drug
resistance will develop. Careful evaluation of the patient's actual adherence
(dietary requirements, daily routine, attitude) is key to cost control and
maintaining viral load reduction. In terms of HIV cost per year of life saved,
drug cocktails are more cost-effective than many other common medical
interventions such as screening mammography.
PMID- 10182005
TI - Personal approach boosts mammograms.
PMID- 10182004
TI - Integrated data system means better maintenance.
AB - The University of Texas M.D. Anderson Cancer Center has consolidated six
databases into one integrated facilities management system. In the first year of
implementation, the system has saved about $150,000 by cutting personel costs and
reducing inventory by 27%. Keys to successful implementation include completely
shutting off the old system before starting up the new one and testing the system
in-house to work out glitches before it went on-line.
PMID- 10182006
TI - Congress likely to restore funding for the Section 202 program.
PMID- 10182007
TI - The 1997 floods. Evacuation and recovery.
PMID- 10182008
TI - 10 reasons to avoid emergency plans.
PMID- 10182009
TI - Crisis communication. What to do when the press comes knocking on your door.
PMID- 10182010
TI - Data disaster. Develop a computer emergency plan.
PMID- 10182011
TI - Skilled nursing facilities reform.
AB - The Medicare prospective payment system for skilled nursing facilities will take
effect with cost reporting years beginning on or after July 1, 1998. HCFA is
working on the implementation details. While final details are not expected to be
published until Summer 1998, the following information has been provided through
HCFA and/or the Nursing Home Case-Mix and Quality (NHCMQ) Demonstration project
(RUGs-III) procedures.
PMID- 10182012
TI - When AIDS enters the workplace. What can you do that is humane, legal and good
for business?
PMID- 10182013
TI - A race/ethnic comparison of career attainment in healthcare management.
PMID- 10182014
TI - Medicare and a national pension proposal.
PMID- 10182015
TI - Untangling the Web. Staying afloat in a sea of information.
PMID- 10182016
TI - Predictive index, early endoscopy cut hospitalization for upper GI bleeding.
AB - Clinicians at Cedars-Sinai Medical Center in Los Angeles have designed a clinical
guideline that uses a scoring index to stratify patient risks, resulting in early
discharge from the hospital for the 70% of patients found to be low risk. A more
ambitious plan at Kaiser Permanente treats GI bleeding on an outpatient basis,
saving an average of $990 per patient. Here are the details, plus the scoring
grid.
PMID- 10182017
TI - Cut costly patient transfers, delays with networked monitoring systems.
AB - Reengineering patient care as needs arise is becoming easier thanks to wireless
monitoring systems. Find out how several health care facilities have put an end
to bottlenecks in the ED and ICU and made more efficient use of patient beds--and
reaped financial savings as a result.
PMID- 10182018
TI - Specialists provide the best, most cost-efficient care for migraine headache
patients.
AB - While the majority of migraine sufferers are treated by primary care providers,
headache specialists can manage migraine much more cost-effectively--in some
cases up to 87% less. Here's why, along with tips for improved treatment and
algorithms for treating migraine.
PMID- 10182019
TI - Reengineer patient care delivery to lower treatment costs.
AB - See how two providers reengineered patient care delivery--and achieved
significant reductions in health care utilization and costs as a result. Here are
the findings from their pilot studies, which provide some useful.
PMID- 10182020
TI - Specialized asthma unit improves care, cuts costs.
PMID- 10182021
TI - Gainsharing model helps align physicians, hospitals.
AB - Physician gainsharing is a hot new incentive arrangement designed to motivate
physicians to develop more efficient care management practices by sharing any
resulting savings with them.
PMID- 10182022
TI - Payer takes a multi-pronged approach to encourage provider participation in
capitation.
AB - A provider community with limited experience in risk-sharing needs more than
encouragement to make a bigger commitment. That's exactly what Blue Cross and
Blue Shield of Iowa offered.
PMID- 10182023
TI - Capitating specialty care poses challenges, but produces savings.
AB - Data Insight: Here's how one Indianapolis-based multispecialty network provides
physicians with data on which to base good clinical and financial decisions,
whether negotiating a contract or tracking utilization.
PMID- 10182024
TI - Are you using data to build valid comparisons? Here's how.
AB - In the quest for needed data and benchmarks under capitation, providers are
discovering comparative analysis software to examine their internal costs, model
a proposed contract, or determine what clinical programs are needed in the
community.
PMID- 10182025
TI - Could capitation's legal 'gray areas' put you at risk?
PMID- 10182026
TI - Accommodating vulnerabilities to environmental tobacco smoke: a prism for
understanding the ADA.
PMID- 10182027
TI - Prenatal genetic screening: the enigma of selective abortion.
PMID- 10182028
TI - 'Tis better to give than to receive: charitable donations of medical malpractice
punitive damages.
PMID- 10182029
TI - Malpractice and other legal issues preventing the development of telemedicine.
PMID- 10182030
TI - The liability of psychotherapists for breach of confidentiality.
PMID- 10182032
TI - Home care and the disability community. Two factions with one goal.
AB - People with disabilities need long-term and community-based services. To date,
that care has been delivered through a medical model of service delivery. The
time is ripe for the home care and the disabled community to look at delivering
care through a social model instead.
PMID- 10182031
TI - Resolving conflicting laws and policy in integrated delivery systems development.
PMID- 10182033
TI - MiCASA (Medicaid Community Attendant Services Act). Amending Medicaid to ensure
home care.
AB - In recent months Congressional interest in community-based care for Americans
with disabilities has gained momentum. The Medicaid Community Attendant Services
Act (MiCASA) would ensure that people with disabilities or a need for long-term
care are able to have a say in what kind of services they receive--and that they
can receive them in the home or community.
PMID- 10182034
TI - Medicare's Catch 22.
AB - People with disabilities need home care to help them leave their homes; if they
actually leave, however, HCFA now says they are no longer homebound and don't
qualify for home care under Medicare. Many policymakers and legislators believe
that the Medicare home health benefit was intended originally to be a post-acute
benefit; however, current law does not support that attitude.
PMID- 10182035
TI - Client-centered care: Texas on the front line.
AB - Client-centered care is a popular concept, particularly for consumers and the
disabled community. Disability advocacy groups are focusing on client-centered
care as a new concept that home care agencies should embrace to provide clients
with more control over their care. However, implementing this strategy might not
be as easy as it sounds.
PMID- 10182036
TI - Life goes on--with planning and help.
AB - The debate around care for someone with a disability focuses on who directs that
care. Several families have found that creating a team with home care providers
allows planning that ultimately gives patients a lot of freedom--freedom to live
full and rich lives.
PMID- 10182037
TI - What to do for wandering.
AB - Individuals with Alzheimer's disease eventually suffer many disabling behaviors,
one of which is wandering. Using common sense tips helps providers and family
caregivers manage this behavior.
PMID- 10182038
TI - Home care in Finland for people with disabilities.
AB - In Finland individuals with disabilities have two sources of care, depending on
their degree of disability: services based on the Social Welfare Act or assisted
living. Workers learn that whatever services they provide need to be based on the
needs dictated by an individual's disability rather than on outside regulations.
PMID- 10182039
TI - Austria's provision for long term care.
AB - In 1993 Austria adopted a social welfare system of health care guaranteeing
social security for its citizens. This decisive plan may well serve as an example
for other European nations for many reasons.
PMID- 10182041
TI - Long-term care programs for people with disabilities.
PMID- 10182040
TI - Child protection at home: a Finnish model.
AB - When applied to a new social services program in Finland, the term home care has
a whole new meaning. The Alvari home care project combines intensive home care,
psychology and social work, and social rehabilitation, all with the purpose of
increasing child protection.
PMID- 10182042
TI - A coalition of caring: the future of long-term care.
PMID- 10182043
TI - Justin Dart. Making a difference. Interview by Val J. Halamandaris.
PMID- 10182044
TI - Direct dial to dispatch. Automated Collision-Notification System provides
immediate access to medical care.
PMID- 10182045
TI - Safety and the field/dispatch connection.
PMID- 10182046
TI - Emergency medical dispatch: a changing profession.
PMID- 10182047
TI - Spirituality and healing in EMS.
PMID- 10182048
TI - A view from the inside. Part two: Paradox in protocols.
AB - In this second installment of a three-part series, Hitschler, a freelance
illustrator/writer and former EMT with a large municipal agency, shares with
readers a series of paradoxical calls she ran, from those where patients were
undertreated or treated unfairly, to those where patients were overtreated for
what turned out to be minor ailments. Finally, Hitschler balances these
experiences with a positive account of her professional relationship with "Mark,"
an experienced EMT who impressed her with his compassionate patient care.
PMID- 10182049
TI - Meeting the challenge. EMS Magazine honors Eureka (MO) Fire Protection District.
PMID- 10182050
TI - Compassion: the core of patient care.
PMID- 10182051
TI - Defending against violence in hospitals.
AB - The authors examine the rise of violence in the healthcare setting and present
some practical methods for identifying high-risk individuals and reducing the
incidence of violence. Some commonsense strategies are presented to help
healthcare security professionals combat workplace violence.
PMID- 10182052
TI - Training parents to protect their children from abduction, kidnapping, or sexual
molestation.
AB - The author discusses the role hospital security directors should play in assuring
parents to be ever vigilant in protecting their children from child predators.
Become an advocate for child safety, he advises.
PMID- 10182053
TI - Initiating a chaplaincy program for a hospital police department.
AB - The authors discuss the creation of a police chaplain program at their hospital-
why it was needed, the preparations that were necessary, the recruitment process,
and the important role the police chaplain plays.
PMID- 10182054
TI - The security professional--take advantage of all opportunities.
PMID- 10182055
TI - Hospitals present a complex security challenge.
AB - Healthcare violence is increasing while funding is shrinking. The author
discusses the various security issues involved, the concept of funneling, and the
role security directors should play in this environment.
PMID- 10182056
TI - NIOSH: new facts about violence against healthcare workers and security officers.
AB - The author reviews what he feels are the most significant findings of NIOSH and
other sources, and presents details of programs designed to prevent healthcare
workers from becoming victims of crime.
PMID- 10182057
TI - Dealing with hostility: a war of words.
AB - If security officers can be provided with more understanding of why people act
the way they do, the training needed to respond to those actions, and the verbal
and physical skills needed in almost all situations, injuries will be reduced and
security forces will be able to deal with hostility and win "the war of words,"
says the author.
PMID- 10182058
TI - Workplace violence: hostage situations in the healthcare setting.
AB - With hostage situations and workplace violence on the rise in healthcare
facilities, healthcare administrators and security professionals must work
towards combating and defending against these acts. The author discusses these
hostage situations, their causes, contributing factors, locations where they
occur, and strategies to prevent hostage and other violent situations. He
provides guidelines on establishing a hostage plan and tips on surviving a
hostage situation.
PMID- 10182059
TI - Workplace violence and domestic violence: a proactive approach.
AB - Hospitals must have a workplace violence prevention plan, one that includes
domestic violence, says the author. She examines workplace violence--particularly
from the perspective of the employee/environment suffering the intrusion of
domestic violence. Examples from her hospital's "Safe Workplace"/Domestic
Violence response plan are presented.
PMID- 10182060
TI - Security departments and employee assistance programs: an effective alliance
against domestic violence.
AB - The authors discuss the collaboration of the Police and Security Department and
the EAP at Massachusetts General Hospital to deal with domestic violence.
Findings from a research study are presented.
PMID- 10182061
TI - Psychiatric patients: premises liability and predicting patient elopement.
AB - Hospitals, says the author, need to be aggressive about properly supervising
psychiatric patients and protecting themselves against potential liability
involving the actions of such patients. The characteristics of elopers and
preventing elopement are also discussed in this article.
PMID- 10182062
TI - Implementing an effective security team.
AB - The author describes her hospital's decision to implement a security team--why it
was needed and what was involved-- and discusses future plans.
PMID- 10182063
TI - A systematic approach to identify, assess and address workplace violence.
AB - To address workplace violence, says the author, healthcare facilities must employ
a proactive and multidisciplinary approach. Leadership commitment, training and
education, communication, assistance initiatives, policies and procedures, and
effective use of security are crucial.
PMID- 10182064
TI - Integrating safety requirements with security operations: a painless approach.
AB - By "crossing over" into the safety arena, says the author, a healthcare security
department can not just survive but actually thrive, as well as improve the level
of services offered at the facility.
PMID- 10182065
TI - Rape: medical and legal information.
AB - The author explores the topic of rape in order to help security directors and
rape victims better understand the medical and legal procedures a victim might
experience. He describes how a rape case might be handled and what to expect.
PMID- 10182066
TI - Officer training, as seen from the Pine Tree.
AB - The Pine Tree Chapter of IAHSS has been dedicated to educating officers, says the
author. The Chapter has developed officer training programs and achieved passing
rates of 96%. In the fall of 1997, the Chapter sponsored a supervisory training
course. This article explores how the programs were developed, obstacles
involved, and how these obstacles were overcome.
PMID- 10182067
TI - New, renovated ERs feature technology, staff deployment, 'safe' rooms.
PMID- 10182068
TI - How new garage at SF General has reduced parking area crimes by 50%.
PMID- 10182069
TI - An interview with: Ira S. Somerson on the role of outside consultants in
enhancing a hospital's security program.
PMID- 10182070
TI - County hospital system employs chaplain for its police/security officers.
PMID- 10182071
TI - Bomb threats and searches: time to reassess procedures and retrain employees.
AB - Bomb threats by unstable persons or pranksters and actual bomb detonations by
activists have been fairly frequent occurrences in schools and medical clinics,
but they take place in hospitals as well. According to the latest IAHSS survey of
221 hospitals, approximately 93 bomb threats were reported in 1995--down from 132
the previous year. Despite this drop, however, more recent incidents of bomb
detonations have security experts preaching preparedness. "With the levels of
international terrorism and the potential for internal terrorism, we need to
revisit these issues," says Tom Kramer, partner, Colling & Kramer Consulting
Associates in Healthcare Security, Northville, MI. "I remember, for a time, when
I was working for Henry Ford Health System, we would not have any bomb threats.
We went from a lot in the 1960s to just one or two every few years, which were
usually related to a disgruntled patient or employee. Now, in light of recent
incidents, we have to take everything a lot more seriously." In this report,
we'll review some proactive steps that hospitals in one area are doing and
present some advice from experts in dealing with callers who make bomb threats.
PMID- 10182072
TI - Safety pros: lift teams, transfer devices reduce costly back injuries.
PMID- 10182073
TI - A predicate for automatic suspension. Cal. Assembly Bill 563 [1997].
PMID- 10182074
TI - Applicability of HCQIA continues to confuse litigants and counsel.
PMID- 10182075
TI - Foley catheter prices poised to rise.
PMID- 10182076
TI - Few hospitals are ready for the year of the UPN.
PMID- 10182077
TI - Software aids in managing cleaning logistics.
PMID- 10182078
TI - Hospital balks at endless service contracts.
PMID- 10182079
TI - The trauma bus stops here.
PMID- 10182080
TI - Packs, bags, kits & more.
PMID- 10182081
TI - Shots fired ... children down.
PMID- 10182082
TI - The truth about volunteer incentives. The pros and cons of administrating an EMS
volunteer incentive program.
PMID- 10182083
TI - A new view on intubation training.
PMID- 10182084
TI - Dangerous liaisons.
PMID- 10182085
TI - Can Washington cure sick nursing homes?
PMID- 10182086
TI - Medical ID plan stirs fears of Big Brother. Interview by Dana Hawkins.
PMID- 10182087
TI - Children's television viewing, body fat, and physical fitness.
AB - PURPOSE: The study examines the relationship between children's television (TV)
viewing and physical fitness. DESIGN: Cross-sectional data from questionnaires
and objective measures were analyzed. SETTING: Data were collected during the
fall of 1990 from public elementary school students in a suburban California
city. SUBJECTS: Approximately 98% of eligible students participated. Of these,
10% were dropped due to missing data, yielding a final sample of 284 girls and
304 boys. MEASURES: Children reported their amount of TV viewing on a typical
summer day; parents reported their child's TV viewing on a typical weekday during
the school year. Cardiovascular fitness was the 1-mile run/walk. Body fat was
both the child's body mass index (BMI) and skinfolds. Additional measures
included muscular strength/endurance and flexibility. RESULTS: Mile run/walk
times were associated with both parental (eta 2 = .051 and .031 for boys and
girls, respectively) and child reports (eta 2 = .020 and .028) of the child's
amount of TV viewing. Parental reports, but not child reports, of the child's TV
viewing were related to BMI (eta 2 = .041 and .058) and skinfolds (eta 2 = .050
and .029). Neither measure of children's TV viewing was related to muscular
strength/endurance or flexibility. CONCLUSIONS: Children's TV viewing seems to be
weakly and inconsistently related to various components of physical fitness.
However, given the tracking of cardiovascular disease risk factors from childhood
into adulthood and the high proportion of children who watch television, these
relationships are worthy of further study.
PMID- 10182088
TI - Spousal similarities in fruit and vegetable consumption.
AB - PURPOSE: To explore similar patterns of fruit and vegetable consumption between
health center employees and their spouses. DESIGN: Cross-sectional mailed survey
assessing frequency of fruit and vegetable consumption, as well as demographics
and knowledge, attitudes, access, and social support related to fruit and
vegetable consumption. SETTING: Six Massachusetts health centers. SUBJECTS: Two
hundred eleven health center employee/spouse pairs (422 individuals). MEASURES:
The kappa statistic measured agreement in fruit and vegetable consumption between
employees and spouses. The Spearman rho coefficient measured correlations for
individual responses. Multiple Linear Regression Models examined variables that
explained fruit and vegetable consumption level differences. RESULTS: Response
rate was 59%. Mean fruit and vegetable daily intake was 4.68 and 4.30 servings
for employees and spouses, respectively. Over 75% of employee and spouse
estimates measuring fruit and vegetable consumption-related information, on
average, were within one survey response category of each other. Knowledge,
attitudes, and access indices were significantly correlated with fruit and
vegetable consumption for both employees and spouses. The social support index
was significantly correlated with fruit and vegetable consumption only for the
spouses. Differences in knowledge, attitudes, and access indices between
employees and spouses helped to explain different fruit and vegetable consumption
levels. Nonresponse, selection, recall, and seasonal reporting biases may limit
the findings' generalizability. CONCLUSIONS: The effectiveness of worksite
nutrition interventions may be improved by involving family/household members.
PMID- 10182089
TI - Formative, process, and intermediate outcome evaluation of a pilot school-based 5
A Day for Better Health Project.
PMID- 10182090
TI - Dietary fat consumption in a cohort of American adults, 1985-1991: covariates,
secular trends, and compliance with guidelines.
AB - PURPOSE: To examine compliance with the guideline for dietary fat (i.e., 30% of
total daily colonies) and covariates of fat intake in a cohort of adults using
both 24-hour recall and food frequency questionnaire (FFQ). DESIGN: Prospective,
observational cohort study over 5 years. SETTING: Community-based sample in Reno,
Nevada. SUBJECTS: Equal numbers of male and female, lean and overweight adults (n
= 508), recruited from 1985 to 1986, of whom 348 completed all relevant surveys.
MEASURES: Subjects underwent repeated anthropometric measures and completed
extensive surveys on diet, weight cycling, lifestyle, and physical activity.
RESULTS: Mean fat intake by 24-hour recall declined from 36.9% to 33.6% of
calories between years 1 and 5 (p < .001), while calorie intake increased (p =
.2). As measured by FFQ at year 2, mean fat intake was 39.1% of calories, and
only 11.8% of subjects were in compliance with the guideline for dietary fat
intake. Fat intake by FFQ at year 2 was statistically higher than by 24-hour
recall in year 1 for lean women (p = .02) and lean men (p = .02), but not for the
overweight of either gender, and was significantly higher than the year 5 24-hour
recall for all categories of gender and weight (p < .001). Calorie intake,
gender, and body mass index were significant in regression models that explained
less than 10% of total variability in fat intake (r2 = .08; p < .01).
CONCLUSIONS: Compliance with the nationally recommended level of dietary fat
intake was poor in this cohort, especially as measured by FFQ. Variability in fat
intake was largely unexplained by host characteristics, including education.
Further study is required to corroborate secular trends in population fat intake,
elucidate the determinants of such intake, and identify cost-effective strategies
for reducing the consumption of dietary fat.
PMID- 10182091
TI - Project Salsa: development and institutionalization of a nutritional health
promotion project in a Latino community.
AB - PURPOSE: Project Salsa was a community-based effort seeking to promote health
through nutritional behavior change in a Latino community of San Diego,
California. The purpose of this article is to report on program factors related
to long-term institutionalization of Project Salsa interventions. DESIGN: Project
Salsa was a demonstration rather than an experimental project. To ensure maximum
sensitivity to the needs and values of the community, Project Salsa began with an
extensive health needs assessment, including development of an advisory council,
telephone survey, archival research, and key informant interviews. SETTING:
Project Salsa interventions took place in San Ysidro, California, located near
the U.S.-Mexico border adjacent to Tijuana from 1987 to 1992. SUBJECTS: The
intervention community had 14,500 residents, of which nearly 83% were Latino.
INTERVENTIONS: Interventions included coronary heart disease risk factor
screenings, meal preparation classes, newspaper columns, point-of-purchase
education, school health and cafeteria programs, and breast-feeding promotion.
MEASURES: Institutionalization of intervention components. RESULTS: Two of the
interventions, the risk factor screenings and school health programs, are still
in operation 4 years after the end of project funding. CONCLUSIONS: Four factors
common to institutionalized components are presented in the paper.
PMID- 10182092
TI - Retina and vitreous disorders.
PMID- 10182093
TI - The systemic evaluation of acute retinal artery occlusion.
AB - Acute retinal arterial occlusion is an ophthalmic condition that is associated
with a high prevalence of systemic disease. Recent studies have demonstrated that
significant numbers of patients with acute retinal arterial occlusion have both
hemodynamically significant carotid artery stenosis and cardiac pathology that
necessitates systemic therapy. Furthermore, emerging evidence show that
coagulopathies and hyperhomo-cysteinemia may be responsible for acute retinal
arterial occlusion. In this paper, we review recent scientific evidence that
supports that adoption of specific guidelines for the systemic evaluation of
acute retinal arterial occlusion.
PMID- 10182094
TI - Surgical management of posteriorly dislocated silicone plate intraocular lenses.
AB - Silicone plate intraocular lenses do not adhere to the lens capsule and are
placed under tension by postoperative contraction of the capsular bag. Recent
reports suggest that a defect anywhere in the capsular bag can potentially lead
to delayed posterior dislocation of silicone plate intraocular lenses. These
implants are more difficult to grasp and manipulate inside the eye than
traditional polymethylmethacrylate lenses and therefore, require special
microsurgical techniques. Given sufficient anterior capsular support, posteriorly
dislocated silicone plate implants can be repositioned in the ciliary sulcus and
do not necessarily require intraocular lens exchange. With proper vitreoretinal
surgical techniques, posteriorly dislocated silicone plate intraocular lenses can
be repositioned or exchanged with excellent visual results and an acceptably low
complication rate.
PMID- 10182095
TI - Complications associated with posterior staphyloma.
AB - Macular degeneration can result in legal blindness among those with progressive
myopia and posterior staphyloma. Programmed photoreceptor death, apoptosis, is
operative in some. Electrophysiologic and psychophysiologic techniques can permit
detection of functional abnormalities before lesions become clinically apparent.
Macular choroidal neovascularization occurs more often in those with moderate
staphyloma than in those with advanced atrophy in the posterior pole. Indocyanine
green angiography is improving our understanding of this complication, which has
been correlated with an increased number of posterior choroidal drainage systems.
One study suggests that surgical extirpation of the neovascular network may be
beneficial in some, but the role of scleroplasty procedures in prevention remains
uncertain. Experimental myopia modeling continues apace, but specific molecular
pathways and their genomic control are yet to be elucidated. Clinically, clear
lens extraction and biphakia techniques are under investigation to offer
refractive relief to the severely myopic patients who are not candidates for
current keratorefractive methods.
PMID- 10182096
TI - Present indications for removal of choroidal neovascular membranes.
AB - Subretinal choroidal neovascularization is an important cause of visual loss in
adults. Removal of choroidal neovascular membranes using relatively new
techniques of subretinal surgery holds promise for improving or stabilizing
vision in some patients. A number of factors have been proposed that may affect
the outcome of subretinal surgery for choroidal neovascularization, including the
degree of involvement of Bruch's membrane, the location of the neovascular
complex relative to the retinal pigment epithelium and Bruch's membrane, the
location of the ingrowth site, and the etiology of the membranes. Although the
surgical techniques are relatively refined, the indications for removal of
choroidal neovascular membranes are still under investigation. This article
reviews the recent and past literature and summarizes the authors' specific
recommendations regarding present indications for removal of choroidal
neovascular membranes.
PMID- 10182097
TI - Plaque radiotherapy for the management of uveal metastasis.
AB - The management of uveal metastasis is focused on both the patient's systemic
condition and the ocular condition. If there is evidence of systemic metastatic
disease, then treatment of the nonocular and ocular metastatic tumors consists of
chemotherapy, hormone therapy, immunotherapy, multiple-site radiotherapy, or
observation. If there is no evidence of systemic involvement, then whole-eye
treatment with chemotherapy, hormone therapy, immunotherapy, radiotherapy, or,
rarely, enucleation is considered. For solitary uveal metastases, plaque
radiotherapy is offered, and if the tumor is small, laser photocoagulation,
resection, or thermotherapy can be used. Inactive uveal metastases are managed by
periodic observation, but active uveal metastases often produce visual loss,
secondary glaucoma, and pain, therefore, treatment is usually indicated.
Radiotherapy is quite effective for control of most uveal metastasis. The
technique of external beam radiotherapy is most often used and is delivered over
a 3- to 4-week period in an outpatient setting. For those patients who fail
chemotherapy, hormone therapy, immunotherapy, or external beam radiotherapy or
those patients with a solitary uveal metastasis, plaque radiotherapy is an
alternative method. Plaque radiotherapy is focal radiotherapy delivered to the
eye in an inpatient setting over a relatively short period of approximately 3
days. Plaque radiotherapy provides satisfactory tumor control, even in eyes that
fail other treatments. Side effects from plaque radiotherapy are comparable to
those from external beam radiotherapy. Importantly, the plaque treatment requires
less of a time commitment for these patients with a limited life expectancy.
PMID- 10182098
TI - Age-related macular degeneration and risk factors for the development of
choroidal neovascularization in the fellow eye.
AB - Age-related macular degeneration (AMD) is one of the leading causes of blindness
in the world. Most of the severe vision loss associated with AMD is due to the
development of choroidal neovascularization (CNV). The specific causes of AMD and
in particular, its neovascular phase, remain uncertain. During the past two
decades a number of large prospective clinical trials, observational
epidemiologic studies, and population-based cohort studies have furthered our
understanding of this blinding ocular condition. The Macular Photocoagulation
Study has received praise for its many contributions in the laser treatment of
neovascular complications of AMD; however, these trials have made other
significant contributions by helping to better define the natural history of AMD,
and in particular, risk factors for the development of CNV in eyes with non
neovascular disease. This type of information may provide significant clues for
researchers regarding disease pathogenesis and identify a high-risk group in whom
to target new treatment strategies. For patients currently diagnosed with macular
degeneration, this information can lead to a better understanding of their
condition and a more accurate prognosis of their ocular health and vision status.
This article reviews information from a variety of sources to investigate
incidence rates and risk factors for the development of CNV in the fellow eye of
patients with AMD and unilateral neovascular maculopathy.
PMID- 10182099
TI - Current concepts in the management of central retinal vein occlusion.
AB - The results of the Central Vein Occlusion Study guide the management of
complications of macular edema and neovascularization. Panretinal
photocoagulation was shown to be beneficial for eyes with at least 2 hours of
iris neovascularization or any angle neovascularization. Grid-pattern laser
photocoagulation for perfused macular edema did not show a significant beneficial
effect. Recently, several reports have suggested restoring venous outflow by 1)
creating a chorioretinal anastomosis, 2) administering recombinant tissue
plasminogen activator, 3) cannulating the retinal vein transvitreally, or 4)
transecting the posterior scleral ring.
PMID- 10182100
TI - Long-term results after low-dose ocular irradiation for choroidal hemangiomas.
AB - Radiotherapy has become increasingly important for the treatment of complicated
choroidal hemangiomas. In recent years, a broad spectrum of different
radiotherapeutic options that either replace or complement the conventional
therapeutic approach by photocoagulation has been recommended. This article
reviews the various treatment modalities and their indications with a special
focus on the long-term outcome of low-dose external beam irradiation.
PMID- 10182101
TI - Retinal complications of strabismus surgery.
AB - The frequency of inadvertent retinal perforation during routine strabismus
surgery has been debated, as patients with such complications are usually
asymptomatic. Recent prospective clinical studies indicate a retinal perforation
rate of 0.4 to 2.8 per 100 cases using modern surgical techniques and materials.
Laboratory studies support close follow-up without treatment as an acceptable
mode of management in the majority of these cases.
PMID- 10182102
TI - Endophthalmitis following open-globe injuries.
AB - Endophthalmitis following open-globe injuries is caused by a specific range of
microorganisms, of which Bacillus sp. and coagulase-negative Staphylococcus are
the most frequent. Risk factors include the presence of an intraocular foreign
body, injury inflicted by organic material, delay in surgery, and the type of
wound involved. Despite important advances in medical and surgical management,
this type of endophthalmitis continues to pose a poor prognosis. In this sense,
we consider prevention to be the best approach. We report our protocols for the
prevention and treatment of endophthalmitis following open-globe injuries, based
on recent experimental studies on the ocular pharmacokinetics of antibiotics and
on multicenter studies of the treatment of endophthalmitis.
PMID- 10182103
TI - Rhegmatogenous retinal detachments with cytomegalovirus retinitis.
AB - The most important ocular opportunistic infection in patients with AIDS is
cytomegalovirus (CMV) retinitis. Management of CMV retinitis has become complex,
as the life expectancy of many patients has increased exponentially. Most retinal
detachments in CMV retinitis are rhegmatogenous in nature. Because of atrophic
changes in the retina and alterations in the vitreous, surgical management of
these detachments leads to a stepladder approach. Options include laser
demarcation, scleral buckle, and vitrectomy with silicone oil. In some patients,
a combination of all three procedures may be necessary. Management in all cases
should be individualized, with the realization that failure of retinal
reattachment may occur.
PMID- 10182104
TI - Treatment outcomes of endogenous fungal endophthalmitis.
AB - Endogenous fungal endophthalmitis may present in a debilitated or otherwise
healthy host, may be increasing in prevalence, and is most commonly caused by
Candida albicans. Recognizing the potential for complications with systemic
amphotericin B use, recent investigators have developed several newer principles
governing the treatment of such cases. For cases of simple choroiditis or very
minimal endophthalmitis (i.e., vitritis), systemic treatment with oral
fluconazole may be effective; however, if vitritis symptoms persist or progress,
vitrectomy allows for better clearing of the organism. Intravitreal amphotericin
B in conjunction with vitrectomy has been advocated by many. The most recent
series have shown that an extended course of oral fluconazole following
vitrectomy without intravitreal amphotericin B affects resolution of infection in
the vast majority of patients. Final visual acuity outcomes depend most on the
site of initial choroiditis. If the macula is spared and preretinal membranes can
be effectively removed, visual acuity results can be exceedingly good.
PMID- 10182105
TI - Vitrectomy for diabetic macular edema associated with a taut premacular posterior
hyaloid.
AB - Diabetic macular edema represents an important cause of visual loss in patients
with diabetes. Although the pathophysiology of diabetic macular edema is unknown,
various demographic, metabolic, and systemic factors have been implicated. More
recently, the role of the posterior vitreomacular relationship has been
evaluated, and studies suggest that posterior vitreous separation confers a
protective effect on the development of diabetic macular edema. Furthermore,
vitreomacular separation occurring in eyes with diabetic macular edema may
facilitate spontaneous resolution of the edema and improvement in visual acuity.
In a subset of patients, diffuse diabetic macular edema can result from a taut
and condensed posterior hyaloid and often responds poorly to focal or grid
pattern laser photocoagulation. Previous studies have reported favorable results
following vitrectomy and peeling of the posterior hyaloid in such cases.
PMID- 10182106
TI - Intact PTH study: shipping frozen vs. unfrozen samples.
AB - DCI Laboratory, Nashville TN compared INCSTAR N-tact PTH SP Kit (INCSTAR Corp.,
Stillwater, MN, USA) results from renal dialysis patients analyzed on frozen
versus unfrozen samples; unfrozen samples were analyzed at 24, 48, and 72 hours
post-collection. There was no statistical or clinical difference in the results
of the frozen samples and unfrozen samples analyzed at 24 hours. Clinics may now
ship unfrozen samples if they arrive within 24 hours.
PMID- 10182107
TI - Weak D effect on estimating fetal-maternal hemorrhage: a case study.
PMID- 10182108
TI - Mycobacterium abscessus peritonitis: a case report.
PMID- 10182109
TI - Tracing our roots: early clinical laboratory scientists and their work--myth and
reality.
AB - OBJECTIVE: To describe the 'real' and 'ideal' clinical laboratory scientist
according to the perceptions of pathologists, clinical laboratory scientists, and
the public during the early years of the profession (1918 to 1942). DESIGN: A
survey of literature on the history of clinical laboratory science was conducted.
References consulted include various books and professional journals. CONCLUSION:
As early as 1920, young women learned, through career guides, that they were
particularly well-suited for performing laboratory work because they possessed a
unique set of attributes which were considered to be desirable qualities in a
clinical laboratory scientist. In addition, magazine articles published in the
popular press in the 1930s and 1940s romanticized laboratory technicians.
Although later articles did present a more realistic description of the work of
the laboratory technician, they continued to portray the occupation in idealistic
terms. Pathologists and laboratory technicians also described the ideal
laboratory technician in professional journals, citing those qualities that were
essential or especially desirable in a competent laboratory technician. The
relationship between the clinical pathologists and the laboratory technician was
described as one of mutual interdependence and integration of responsibilities.
In reality, pathologists maintained strict supervision and control over the work
of laboratory technicians. The 'real' laboratory technician differed markedly
from the 'ideal' prototype created by the public, pathologists, and by laboratory
technicians, themselves.
PMID- 10182110
TI - Calcium, phosphorus, and alkaline phosphatase values of elderly subjects.
AB - OBJECTIVE: To determine if significant gender differences existed between
subjects 65 years of age and older, with regard to calcium, phosphorus, and
alkaline phosphatase levels. DESIGN: A retrospective chart review of laboratory
procedures performed in six different physician practices. The data consisted of
178 subjects representing 92 males and 86 females over the age of 65. DATA
SOURCES: Patient data were obtained from the charts housed in a cardiac care
center. Subjects, with charts preceding them, were referred by a physician to the
cardiac center. The laboratory procedures had been performed previously in the
laboratories of the referring physicians. MAIN OUTCOME MEASURES: After accounting
for variation between laboratories, mean values of calcium, phosphorus, and
alkaline phosphatase were examined to establish if a gender difference existed in
patients over the age of 65. A blocked analysis of variance (ANOVA) was conducted
at the 0.05 significance level. RESULTS: ANOVA analysis yielded significant
gender differences for calcium, phosphorus, and alkaline phosphatase (p < 0.05).
Females over the age of 65 consistently showed higher levels than males over the
age of 65 for all three variables in five of the six laboratories studied.
CONCLUSION: A statistically significant difference was found between the mean
levels of men and women 65 years of age and older for calcium, inorganic
phosphorus, and alkaline phosphatase. Gender and age are important variables to
consider when analyzing and interpreting calcium, phosphorus, and acid
phosphatase levels.
PMID- 10182111
TI - Booze and blood: the effects of acute and chronic alcohol abuse on the
hematopoietic system.
AB - Acute and chronic alcohol abuse are common conditions in patients admitted to
hospitals. Alcohol has widespread direct and indirect effects on the hematologic
system which can mimic and/or obscure other disorders. Leukocyte, erythrocyte,
and thrombocyte production and functions are affected directly. Liver damage
secondary to alcohol abuse also impacts red blood cells also impacts red blood
cells and the hemostatic mechanisms. Nutritional deficiencies are caused not only
by poor dietary habits practiced by alcohol abusers, but by the effect of alcohol
on the absorption, storage, and utilization of several vitamins. Identifying
these numerous effects results in a more comprehensive and clinically accurate
understanding of the patients hematologic status.
PMID- 10182112
TI - Hematologic effects of thrombophilia.
AB - The hematologic effects of thrombophilia are subtle, and when recognized may
provide clues for the diagnosis of hypercoagulation in patients. This article
identifies aberrant, routine test results associated with the diagnosis of
thrombophilia. The future expansion of laboratory testing for thrombophilia
detection is presented in summation.
PMID- 10182113
TI - Hematologic changes associated with infection.
AB - Hematologic data provide information useful in both the detection of infectious
disease and in the monitoring of patients diagnosed with bacterial, viral,
fungal, and parasitic infections. Infection, typically accompanied by
inflammation, results in changes within the hematopoietic system that can be
observed as qualitative and/or quantitative changes in 3 cell lines: Leukocytes,
erythrocytes, and thrombocytes. These alterations to hematopoietic cells are
mediated via the influence of microbial toxins and cytokines on cellular
proliferation, differentiation, and activation.
PMID- 10182114
TI - The proposed use of performance indices to evaluate and compare the "Gish Vision"
membrane oxygenator.
AB - The objective of this investigation was to evaluate and compare the recently
released Gish Vision oxygenator with previously studied oxygenators. We utilized
our previously described membrane oxygenator evaluation techniques as well as
proposed the use of four new performance indices: 1) oxygen transfer index; 2)
shunt fraction index; 3) pressure drop index; and 4) consistency index. We
concluded that the new Gish Vision membrane oxygenator offers the clinician the
highest level of oxygen transfer "reserve" of any oxygenator we have tested. The
use of our proposed performance indices enables the perfusionist to quickly and
objectively compare various oxygenator performance characteristics and make a
meaningful clinical comparison.
PMID- 10182115
TI - The efficacy and safety of a pharmacologic protocol for maintaining coronary
artery bypass patients at a higher mean arterial pressure during cardiopulmonary
bypass.
AB - A recent randomized trial of higher versus lower mean arterial pressure (MAP)
during cardiopulmonary bypass (CPB) showed that higher MAP on CPB was associated
with a lower incidence of overall cardiac and neurologic morbidity and mortality
in coronary artery bypass graft surgery (CABG) patients. Cardiopulmonary bypass
MAP was controlled pharmacologically while CPB flow was held constant for any
given period. The objective of the present study was to assess the efficacy and
safety of this pharmacologic protocol. Two hundred forty-eight patients
participated in the study; the mean age was 65.8 +/- 9.4 years, 20% were women,
and the mean preoperative ejection fraction was 48%. The low-flow corrected CPB
MAP attained for the low and high MAP groups was 56.7 +/- 5.0 mmHg and 77.7 +/-
7.1 mmHg, respectively (p = 0.0001). Major cardiac and neurologic outcomes,
postoperative blood loss, renal dysfunction, intensive care unit (ICU) stay, and
duration of intubation were not found to be significantly associated with any
drug in the pharmacologic protocol. These findings support that the pharmacologic
protocol used to maintain CABG patients at higher MAP on CPB is both efficacious
and safe.
PMID- 10182116
TI - Do different heparin brands influence activated clotting times?
AB - A change in brand suppliers of heparin at our institution resulted in a number of
anecdotal reports of possible differences in potency. Both products are marketed
as heparin sodium extracted from porcine intestinal mucosa. Heparin Leo is 1000
international units (British Pharmacopeia) per ml. while Hepalean is 10,000
United States Pharmacopeia (U.S.P) units per ml. Perfusion records were
retrospectively reviewed for one month periods when Heparin Leo (n = 52) or
Hepalean (n = 61) were used to provide anticoagulation therapy for
cardiopulmonary bypass. Heparin Leo was found to be less clinically potent than
Hepalean. While increasing the initial loading dose of Heparin Leo by 5% (378 vs
398 units/kg-1), the initial post load activated clotting time (ACT) was 17%
lower (556 vs 666 seconds). Heparin units required per kilogram per minute of
cardiopulmonary bypass were 23% higher for Heparin Leo. Additionally 8 of 52
Heparin Leo patients did not achieve an initial post load ACT of greater than 400
secs while this occurred in 2 of 61 patients treated with Hepalean. These results
were statistically significant. British Pharmacopeia and United States
Pharmacopeia heparin reference standards differences are insufficient to explain
the discrepancies observed in this study.
PMID- 10182117
TI - Errors in flow and pressure related to the arterial filter purge line.
AB - The purge line is a necessary component on arterial filters, although its
presence may affect the amount of flow reaching the patient as well as the pump
outlet pressure in the extracorporeal circuit. In-vitro and clinical studies
conducted to investigate these effects with a commonly used purge line showed
that at flows less than 1.5 L/min, rates for pediatric or infant patients, the
purge line diverts as much as 40% of the intended pump flow away from the
patient. A small diameter resistance tube connected in series with the purge line
reduced purge flow such that over 80% of the pump flow reached the patient.
Pressure monitored at the arterial filter port with the purge line open could be
as much as 45 mmHg lower than the pressure measured with the purge line closed to
the filter. Studies should be done to determine if the arterial filter purge line
compromises flow to the patient, and if an additional resistance to the purge
line is appropriate to reduce the flow through it.
PMID- 10182119
TI - Collagen: ubiquitous in nature, multifunctional in devices.
AB - Collagen is a protein that is widely distributed in humans and plays an important
role in many aspects of tissue performance. This versatility is central to the
uses of collagen in biomedical devices. The structure and properties of collagen
and the basis for their biomedical uses are described in this article.
PMID- 10182118
TI - Hematological abnormalities in neonatal patients treated with extracorporeal
membrane oxygenation (ECMO).
AB - The physical process of extracorporeal membrane oxygenation (ECMO) results in
derangement of the hemostatic mechanism, which may lead to increased morbidity,
secondary to the disease process. The purpose of this study was to evaluate the
hematological status of neonates undergoing ECMO therapy, and to evaluate
coagulation tests in predicting hemorrhagic risk. Following Institutional Review
Board approval, 30 patients undergoing ECMO treatment were retrospectively
entered into this study. Medical records were reviewed and indicators of
hemostasis, transfusion, morbidity, and outcomes recorded. Assessment of
coagulation was determined through serial analysis of platelet count, fibrinogen
concentration, prothrombin time (PT), activated partial thromboplastin time
(aPTT), antithrombin III, fibrin split products, D-dimers, plasma free
hemoglobin, activated clotting time, ionized calcium, and thrombelastography
(TEG). Median total transfusion requirements for all patients were 1.79
ml/kg/ECMO hr. Fifty-seven percent of the 30 patients were diagnosed as
coagulopathic according to Extracorporeal Life Support Organization standards.
Patients were separated into either a hemorrhagic group (HEM, > 2.0 ml/kg/ECMO
hr, n = 13) or a nonhemorrhagic group (N-HEM, n = 17), with HEM patients
requiring twice the transfusion volume of N-HEM (p < 0.0001). Hemorrhagic
complications were reported in 53.8% of the HEM patients vs. 35.3% in the N-HEM
group. HEM patients were transfused with significantly greater quantities of
platelets on days 1, 3, 5, and 8 and packed red blood cells on day 7 when
compared to N-HEM (p < 0.05). TEG determination showed significant differences
between groups on days 3 and 6 (p < 0.005), and 8 (p < 0.05). Derangements in
hemostasis resulting from ECMO are profound, with methods of assessing
coagulation complicated by both the variability in patient condition and lack of
specificity of laboratory tests. Interpretation of TEG data has shown to be a
valuable supplement for managing this challenging patient population.
PMID- 10182120
TI - Differing definitions of manufacturer.
AB - Medical device manufacturers marketing in the United States (US) and Europe must
comply with different labelling requirements concerning the indication of
manufacturer on the label. These differences are increased if US labelling
requirements are compared with the practice of own-brand labelling under the
European medical device Directives. This article discusses the differing
requirements.
PMID- 10182121
TI - Problems associated with microbiological validation of sterilization by ionizing
radiation.
AB - Potential solutions to some of the practical problems experienced when validating
products processed by radiation sterilization are discussed in this article. The
standards for validation and routine control of radiation sterilization are to be
revised next year and there is now an opportunity for the industry to influence
the effectiveness of those revisions. Medical device manufacturers are encouraged
to make views known to help ensure a simpler standard that is widely implemented.
PMID- 10182122
TI - Parametric release for EtO sterilization.
AB - The use of microwave spectroscopy as a process-control monitor to measure
ethylene oxide (EtO) is an exciting breakthrough in EtO sterilization.
Technologies employed until now have lacked the specificity or long-term
stability to measure EtO, but microwave spectrometers now in EtO facilities have
shown consistent and accurate results. This article explains the technology.
PMID- 10182123
TI - Choosing an IVD notified body: start now and gain a competitive edge.
AB - Following more than two years of negotiation, the In Vitro Diagnostic Directive
could be nearing adoption by Member States. Manufacturers will then have a short
window of opportunity to obtain the CE mark early in the transition period when
it has real competitive value. This article recommends immediate action and looks
at some of the issues to consider when choosing a Notified Body.
PMID- 10182124
TI - Iontophoresis: an alternative drug-delivery system.
AB - Iontophoresis expands the range of drugs that are available for transdermal drug
delivery. This article looks at the important advantages this technology offers,
such as the ability to rapidly deliver large quantities of large-molecule and
water-soluble drugs. Its potential is illustrated in a review of ideal drug
candidates and results of trials conducted to date.
PMID- 10182125
TI - Sandwich moulding using sequenced screw loading.
AB - Sequenced screw loading is an alternative method for injection moulding two
materials. This article explains the process and outlines the advantages it
offers product designers. Benefits can include reduced cycle times and product
cost.
PMID- 10182126
TI - Hospital for ex-pats underway in China.
PMID- 10182127
TI - PhysiTel announces "One World" program for developing nations.
PMID- 10182128
TI - Hughes supplies system for Canadian health care network.
PMID- 10182129
TI - Japan offers satellite for regional use.
PMID- 10182130
TI - Secretary of State Albright watches as physicians conduct first live Internet
consult between China and U.S.
PMID- 10182131
TI - Governor dedicates network at Denver's University Hospital.
PMID- 10182132
TI - Protect your practice with a Medicare and Medicaid compliance program.
PMID- 10182133
TI - Placing the cornerstone for healthcare professionals' risk management education:
an educational needs assessment.
AB - The risk manager's performance of an educational needs assessment to assist in
determining related training and development elements supports a solid, proactive
risk management program designed to motivate healthcare professionals.
Environmental scanning, needs assessment tool design and development, tool
validation, organizational commitment and ethical considerations are examined. A
sample needs assessment tool is provided.
PMID- 10182134
TI - Managing workers' compensation exposures in healthcare.
AB - Employees in healthcare are exposed to numerous and varied risks that pose the
threat of injury. Management of those exposures by the organization will
ultimately help create a safe environment for staff, patients and the public.
Incorporating workers' compensation into the risk management program is the first
step toward managing and reducing these exposures. This article presents a
suggested outline for a written risk management plan for workers' compensation
exposures.
PMID- 10182135
TI - Detection of improperly positioned feeding tubes.
AB - This article describes potentially disastrous outcomes associated with failure to
determine when nasally inserted feeding tubes are improperly positioned. It also
presents information that is important for risk managers to consider when
developing protocols for testing placement of newly inserted feeding tubes.
PMID- 10182136
TI - Managing risks in managed care environment.
AB - The healthcare environment is rapidly changing as managed care penetrates your
community. Risk management in the office setting is becoming more critical as the
strategies for preventing claims in the first place become more important. It is
time to reexamine the environment that is being created, increase the involvement
of patients in their own care, create documentation systems and recognize when
you are at risk.
PMID- 10182137
TI - Taking it to the people: coalition attacks reuse.
PMID- 10182138
TI - Move over, JCAHO! There's another game in town.
PMID- 10182139
TI - Sky's the limit. Lofty thinkers take materials management to new heights.
PMID- 10182140
TI - Mad to glad. Smart tips on resolving complaints.
PMID- 10182141
TI - Bull's eye! Management tool helps target costs and bag savings.
PMID- 10182142
TI - Mission possible. We won the war against lap chole costs.
PMID- 10182143
TI - Mercury falling. The search is on for substitutes.
PMID- 10182144
TI - Stats. Tracking wear-and-tear: are you on the money?
PMID- 10182145
TI - A bill of rights, or a bill of goods?
PMID- 10182146
TI - Graying America. The needs of a growing population.
PMID- 10182147
TI - From consumer satisfaction to consumer perception of care.
PMID- 10182148
TI - Critical mandates: prevention and health promotion.
AB - Health maintenance organizations are supposed to maintain health, not just
contain the cost of treating illness. Prevention and health promotion are
critical mandates for managed care organizations, including managed behavioral
health plans. More often than not, however, health plans have neglected to
include prevention and behavioral health promotion services within their spectrum
of covered benefits. In this article, the authors explain why there is a growing
trend toward including coverage for prevention and promotion services in managed
behavioral health plans, including the financial advantages and cost-containment
opportunities that result. The article also illustrates several simple and
straightforward models for structuring prevention benefits, managing the
utilization and quality of prevention services, and including community-based
preventive services organizations in provider networks.
PMID- 10182149
TI - Successful behavioral health business development for the millennium.
AB - The business development framework for provider positioning, market share, and
competition has significantly shifted in the late 1990s as providers prepare for
the millennium. The use of the Marketing Four Ps is a helpful tool for providers
to thoroughly evaluate their product/service viability, pricing objectives,
promotional mix, and place accessibility, and will allow organizations to
reposition in their marketplace, maximize market share, and develop new
partnerships with previous competitors.
PMID- 10182150
TI - Mental health parity under managed care. Results to date and implications.
PMID- 10182151
TI - Dialogue. Industry consolidation: what's at stake for consumers and purchasers?
AB - The behavioral healthcare field has undergone massive consolidation, especially
in the last year. Health plans, hospital systems, and community-based
organizations have all been affected. Economists argue that consolidation is a
logical consequence of the current, competitive healthcare market. But consumers
and purchasers wonder if the mergers and acquisitions will benefit them.
Efficient markets are supposed to stimulate competition in ways that reward
purchasers and consumers of services. When prices go down and quality improves as
a result of competitive market forces, then the market has functioned properly
and has served its purpose. Behavioral healthcare, however, is an essential human
service, not a commodity. And the consumers and purchasers of healthcare are
typically not the same person or entity, which also makes the healthcare market
different from the markets for cars, computers, food, or any other type of
consumer product. More than 100 million Americans now receive managed behavioral
health benefits from only three companies. With such intense power concentrated
in the hands of such a small number of providers, the time has come to evaluate
the impact of the consolidation trend. In the following dialogue article,
leaders, representing different interest groups review the benefits and risks of
massive industry consolidation, and propose solutions to the critical challenges
that it raises.
PMID- 10182152
TI - A primer on outcome measures for children's services.
PMID- 10182153
TI - Access to atypical antipsychotics: a public payor's perspective.
PMID- 10182154
TI - Group practice innovations and the cost of quality in behavioral health services.
AB - Group practices have enhanced the accessibility and quality of care through
continuous innovation and performance improvement initiatives. However,
sustaining a quality infrastructure can be costly. Will purchasers and consumers
demand a group-model delivery system that provides accessible, effective,
accountable, efficient, and coordinated care when network-models with little
overhead can provide basic services for less? Here's how groups in the Institute
for Behavioral Healthcare's (IBH) Council of Behavioral Group Practices are
innovating to sustain excellence and superior performance.
PMID- 10182155
TI - Spectacular accomplishments and disappointing mistakes. The first decade of
managed behavioral care.
PMID- 10182156
TI - Rethinking LOS: focus on process improvement and the days will drop.
AB - Some experts say the increasing emphasis on length of stay as a measure of
quality improvement has obscured the need to develop efficient and effective
process improvements. Indeed, some argue that length of stay shouldn't be a
concern. If your process improvements work, lengths of stay will take care of
themselves. Focusing specifically on length of stay reduction won't necessarily
lower your costs; indeed, it may just shift the costs to another part of the
delivery system. Even Milliman & Robertson, the Seattle-based actuarial firm made
infamous by its length-of-stay guidelines, emphasizes the need to judge case
individually and to make allowances for patients with comorbid conditions.
PMID- 10182157
TI - CM staffing survey quantifies today's norms.
PMID- 10182159
TI - CQI project improves discharge process.
AB - At Gibson Rehab Center in Williamsport, PA, a continuous quality improvement
project to bolster the institution's discharge planning process has resulted in
increased satisfaction and an award for quality. The 15-month project was
spearheaded by a multidisciplinary team charged with identifying areas that had a
significant impact on customer service and suggesting better ways of delivering
that service. Among the changes the group suggested were establishing a weekly
discharge planning group for new neuro patients, assigning a discharge
coordinator for each treatment team, and creating an interdisciplinary
communication sheet for the home health therapy staff.
PMID- 10182158
TI - Pathway for uncomplicated cardiac surgical patients.
PMID- 10182160
TI - Can you untangle web of outcomes information demands?
PMID- 10182161
TI - What customers want to know about your program.
PMID- 10182162
TI - Brain injury program meets needs of teens.
PMID- 10182163
TI - Alternative medicine: a big unknown under capitation.
PMID- 10182164
TI - Capitated linen management a 'no-brainer' for hospitals.
AB - In their efforts to cut costs under managed care, are hospitals and health
systems overlooking obvious candidates for capitation? Here's how one provider
put some dollars to its bottom line with a capitated linen services agreement.
PMID- 10182165
TI - 'Standardized patients' can combat practice variations.
AB - When a group of physicians in Montreal used four "standardized patients" to
assess physician resource utilization and visit costs, they discovered wild
variations. Could a similar program improve practice patterns and drive down
utilization in your organization?
PMID- 10182166
TI - 'Mystery shoppers' may uncover customer service deficiencies.
PMID- 10182167
TI - Study examines influence of PCP compensation method on cost, utilization of
services.
AB - Data Insight: Opponents of risk contracting sometimes suggest that capitated
provider withhold patient care to protect their own bottom lines. A recent study
refutes that notion--with some qualifications.
PMID- 10182168
TI - Diabetes nurse case manager program lowers costs, improves glycemic control.
AB - Capitation demands that health plans and provider systems take a population-based
view. A diabetes intervention piloted by a group of Florida physicians shows the
value of this approach.
PMID- 10182169
TI - Alleged abuses in health care in the 1990s: a critical assessment of causation
and corrections.
AB - Allegations of fraud in the health care field are being directed at a multitude
of providers. This article, which follows an earlier one published in The Health
Care Supervisor (16:2), seeks to address three questions surrounding the issue:
what manner of fraud has occurred in the health care industry; which methods are
being employed by our nation's legal system to address the problem, and, in the
growing number of instances in which culpability is unclear, how alternative
dispute resolution can be utilized to both address and resolve problems that
arise.
PMID- 10182170
TI - Staff career development programs: the role of supervisors.
AB - Today's health care institutions need employees who are knowledgeable, committed,
competent, motivated, and flexible. New management styles, mission statements,
and incentives have little impact on these essential characteristics if they are
not supplemented with career development programs. This article provides an
overview of career development programs and the elements necessary for successful
applications of these programs, with an emphasis on the importance of mentoring.
PMID- 10182171
TI - Cost analysis of adaptive seating systems in a specialty seating clinic.
AB - Adaptive seating systems are essential for individuals with severe physical
limitations to access community, vocation, and education venues. However,
financial constraints threaten the existence of many specialized seating clinics.
Due to concerns about the fiscal stability and viability of the university of
Tennessee Seating Clinic, the authors were asked to conduct a cost analysis and
to make recommendations concerning the future of services at the clinic. The
authors reviewed 18 seating systems, analyzed extensive financial data, observed
administrative procedures, and made recommendations. In response to this report,
the university administration made major revisions to this clinic.
PMID- 10182172
TI - Establishing the link: relating a 360 degree management assessment and
development process to the bottom line.
AB - The challenges facing hospital management today demand that both medical and
nonmedical personnel be as productive as possible, with the ultimate goal of
establishing a link between employee growth and return on investment, while
maintaining the highest standards of patient care Using two case studies--River
Parishes Hospital and Manatee Hospital--this article discusses how 360-degree
assessment programs can contribute to individual and team development as well as
the bottom line. The article will show how ACUMEN Skills, a 360 degree assessment
tool, implemented with appropriate facilitation, helped to increase productivity
and efficiency, improve relationships among staff at all levels, reduces
expenses, and strengthen the bottom line.
PMID- 10182173
TI - Training and retaining Shasthyo Shebika: reasons for turnover of community health
workers in Bangladesh.
AB - Shasthyo Shebikas (SS) are community health workers forming the core of BRAC's
Essential Health Care (EHC) programme. The SS dropout was 44 percent for study
area and 32 percent for EHC programme. The SS discontinued their work due to lack
of time, lack of "profit", and family's disapproval. The effects of the dropouts
were decreased achievement of targets, and a loss of money in the amount of $24
(U.S.) per dropout SS for their training and supervision. The SS retention may
increase if EHC strictly adheres to its existing guidelines when selecting
trainees, and if it highlights during SS training that SS; s first and foremost
role will be as that of a volunteer and then of a salesperson.
PMID- 10182174
TI - I'm not paranoid: they are out to get me.
AB - Paranoid thinking is a common phenomenon that is experienced in everyday life and
consequently can found among health care professionals and employees. Health care
professionals sometimes experience paranoid thoughts about the actions and
intentions of others in the workplace. It is important for the health care
professional to understand paranoid thoughts and to respond appropriately if
these feelings are experienced. Appropriate action can be important in
maintaining the professional's image in the workplace.
PMID- 10182175
TI - Please don't shoot me: I'm only the change agent.
AB - The change agent is a necessity rather than an option for a hospital's future
success in the volatile managed care environment. While his or her message may be
unpopular and tactics unconventional, the change agent had the extraordinary
confidence and capacity to move an organization from analysis to synthesis. This
article describes the change agent's makeup and method of operation as well as
the 10 most potent tools and insights for effecting sustainable change.
PMID- 10182176
TI - Applying continuous quality improvement and human performance technology to
primary health care in Bahrain.
AB - This article discusses management and organizational development lessons learned
as the result of an innovative primary health care project (Sitra Project),
sponsored by the Ministry of Health, Bahrain. The improvement models commonly
referred to as continuous quality improvement (CQI) and human performance
technology (HPT) were applied to effect significant improvement in a number of
control variables while maintaining or reducing operational costs. The most
important lessons are that improvement can be made through CQI and HPT; that
participation, empowerment, and accountability are the foundation of success;
organizational decisions must be based on relevant data; strategic commitment of
top management must underpin improvement must underpin improvement efforts;
turfism and threats to power and status can derail change efforts; and the future
will always remain uncertain.
PMID- 10182177
TI - Fattened and flattened: the expansion and contraction of the modern organization.
AB - In a changing world, organizations must change as surely as individuals must
change. Recent years have been seen an increase in organizational "flattening",
the tendency to shrink the organizational structure through the removal of layers
in the hierarchy. Today flattening is especially prevalent in health care,
particularly in hospitals, as the industry adjusts to various external pressures
through mergers, acquisitions, and sometimes closures. While organizational
growth, or "fattening", is usually slow, occurring sometimes imperceptibly over
long periods of time, flattening is usually abrupt and therefore painful.
Especially affected are first-line supervisors and middle managers. The
supervisor's main defense against obsolescence in this new environment is to
become as multifaceted as possible, recognizing that one's future security lies
not in constancy and specialization but rather in flexibility and adaptability.
PMID- 10182178
TI - The role of flow cytometry in improving biocompatibility in transfusion medicine.
AB - In transfusion medicine, blood and blood components, donors and patients are
increasingly confronted with biomaterials. The need to understand the response of
human blood to contact with these artificial surfaces has led to multiple studies
on the biocompatibility of biomaterials. Up to this time, these investigations
have predominantly been performed using physical, immunological and biochemical
methods. Many of these approaches are useful in investigating the multiple
factors involved in blood-biomaterial interactions. However, they always reflect
the overall behaviour of whole cellular populations in local or systemic
reactions. The application of multiparameter flow cytometry, on the other hand,
provides insight into antigenic expression and changes at the single-cell level.
Therefore, the technique of flow cytometry represents a new and powerful way of
analysing and improving the biocompatibility of these materials in blood
contacting applications in this field.
PMID- 10182179
TI - Synchronization of plasma exchange and adjuvant treatments.
PMID- 10182180
TI - Prevention of infections transmissible by blood derivatives.
AB - Agents that are transmissible by blood or its derivatives typically have long
incubation periods, may often be asymptomatic for several years and can set up
carrier or latent persistent infections. Examples are hepatitis B virus (HBV),
hepatitis C virus (HCV), the human immunodeficiency viruses (HIV 1 and 2) and
cytomegalovirus. The prevention of transfusion-transmitted infection (TTI) is
based on the exclusion of potential blood donors who are not fit and well, the
education of donors to exclude themselves if they are at risk of contracting
TTIs, the laboratory screening of all blood donations for evidence of infection
with a range of potential TTIs, physical removal of white cells in those cases
where the agent is cell associated, viral inactivation procedures for pooled
plasma derivatives, detection of viral genomes in plasma pools and the avoidance
of unnecessary transfusions.
PMID- 10182181
TI - Statistical process validation of leucoreduced blood components.
PMID- 10182182
TI - HIV-1 detection and subtyping by PCR and heteroduplex mobility assay in blood
donors: can these tests help to elucidate conflicting serological results?
AB - Testing blood donors for the human immunodeficiency viruses (HIV-1 and 2),
requires serological tests that are frequently inconclusive. Peripheral blood
mononuclear cells of 50 blood donors with the screening test (ELISA) reactive to
HIV-1, but with indeterminate results in the first Western Blot (WB) performed,
were submitted to the polymerase chain reaction (PCR) and heteroduplex mobility
assay (HMA), a nonsequencing method that can distinguish between HIV-1 subtypes
(A to I). PCR amplification of HIV-1 env gene regions has been obtained in 12
(24.0%) samples. HMA of the amplified DNA showed that 12 belonged to HIV-1 B
subtype and one to F subtype. PCR testing of the amplified DNA helped to
elucidate doubtful serological results and HMA proved to be a relatively simple
and rapid way of subtyping HIV-1 for epidemiological purposes.
PMID- 10182183
TI - Indications for a cost-saving policy in routine flow cytometry.
AB - Flow cytometry has known a growing popularity in last decade as an intriguing
research and diagnostic tool, favoured by the availability of newly developed
monoclonal antibodies directed against cell surface antigens. Unfortunately,
equipment and reagents costs are still prohibitive, and it does not allow a more
widespread use of this technology. We realised that most producers suggest to add
the same amount of reagents irrespective of the real number of target cells, and
this is particularly true if the lysed whole blood technique is used. We
investigated if an "individualized" concentration of reagents, based on the real
number of MNC to be stained, could have allowed us to achieve qualitative
satisfactory results with a concomitant reduction in costs. We studied four
groups of individuals: 259 healthy subjects (239 blood donors and 20 volunteers)
and 10 HIV+ patients. Our results suggest that lower amounts of reagents could be
used, at least in some routinary cytometric analysis, simply following providers
instructions (i.e. 1 microL of monoclonal antibody/1 x 10(5) MNC).
PMID- 10182184
TI - The transfusion audit as a tool to improve transfusion practice: a critical
appraisal.
AB - Transfusion audits have a long history and they are required by many regulatory
agencies. These audits have been touted as effective in reducing unnecessary
transfusions as evidenced by many published articles on the subject. Most of
these studies, however, have one or more flaws in their design including the use
of historical controls, disregard of the Hawthorne effect, use of multiple
interventions, and publication bias. Studies differ in the baseline rate of
inappropriate transfusions and have different methods of measuring these rates.
There is also little data on how long the effect of implementing a transfusion
audit system may last. Transfusion audits appear most successful when there is a
high baseline rate of inappropriate transfusions and interventions other than the
audit itself are performed. Individual institutions should critically evaluate
whether or not their current system of transfusion audits is useful.
PMID- 10182185
TI - The red blood cell utilization review experience.
AB - The Joint Commission on Accreditation of Healthcare Organizations catalyzed peer
review of blood transfusion and gave it new form in 1984. This process became
mostly comprehensive, retrospective, bi-level, and chart-based with an initial
screening phase followed by physician- review. Studies were identified and
evaluated to test the efficacy of this process, which has recently come under
question. In two-thirds of the studies, transfusions were judged appropriate in
over 90% of cases. In most hospitals reporting, there were no inappropriate
transfusions. It is concluded that the process often results in too few
inappropriate cases to readily identify opportunities for improvement.
PMID- 10182186
TI - Availability of clotting factor concentrates in genetically engineered form.
AB - Recombinant clotting factor concentrates provide new opportunities for the
treatment of hemostatic disorders such as haemophilia A and B and von Willebrand
disease. This article briefly reviews the clinical results of currently available
products, the development of concentrates of clotting factor IX and von
Willebrand factor and the outlook of second generation products (e.g., deletion
mutants) and gene therapy of haemophilia. Further elucidation of the
structure/function relationship of plasma proteins will probably lead to a new
category of medicinal products for the treatment of bleeding and thrombotic
diseases.
PMID- 10182187
TI - The transfusion audit as an educational tool.
AB - Audits of transfusion used as educational tools can improve transfusion
practices. Effective audits must first identify problem(s) in transfusion
practice and must then include as educational target, the attending physician.
Educational methods that have been shown to the effective include: (1) meeting
briefly one-on-one with physicians, (2) teaching at scheduled conferences, (3)
making daily clinical rounds on patients who receive transfusion, (4) concurrent
review of orders for transfusion prior to issue of the blood product and (5)
installing algorithms and guidelines in the operating room. Transfusion practices
improved with these educational audit methods.
PMID- 10182188
TI - Future directions in utilization review: the role of transfusion algorithms.
AB - Transfusion practice guidelines and retrospective utilization review have been
ineffective in curtailing the inappropriate use of blood and blood products,
particularly in cardiac surgical patients. Patients undergoing cardiac surgery
with cardiopulmonary bypass (CPB) are at increased risk for excessive
perioperative blood loss requiring transfusion of blood products. Recent
evaluations have focused on the use of point-of-care coagulation assays for
patient-specific therapy. Blood component administration in patients with
excessive post-CPB bleeding is generally empiric, in part related to the times
required to perform of laboratory-based tests. Methods are now available for
rapid, on-site assessment of coagulation assays to allow appropriate, targeted
therapy for acquired hemostatic abnormalities. Recent studies indicate that a
rapid evaluation of thrombocytopenia and coagulation factor deficiencies, coupled
with transfusion algorithms, can facilitate the optimal administration of
transfusion-based therapy in patients who exhibit excessive bleeding after CPB.
The use of point-of-care assays and transfusion algorithms may provide an
effective concurrent method of utilization review of blood products in the
surgical setting.
PMID- 10182189
TI - A reappraisal of economic evaluation of pharmaceuticals. Science or marketing?
AB - In pharmacoeconomic research sponsored by companies, there is an obvious tension
between the desire to undertake studies to show a marketing advantage and the
desire to adhere to good scientific principles. This tension was explored in an
early issue of PharmacoEconomics and is now revisited 5 years on. Bias is still
perceived to be a major problem in industry-sponsored studies, both by healthcare
decision-makers and journal editors. However, the debate about bias has matured
over the years. Also, actual evidence of bias in study methodology is sparse,
although biases in study topic selection and in the use, in promotion, of study
results have been found. A number of constructive suggestions have been made in
the last 5 years for reducing potential bias. These include developing
methodological guidelines and standards, improving the peer review process,
clarifying contractual relationships between sponsors and analysts, and ensuring
appropriate use of studies in promotional activities. However, further
initiatives could be undertaken. These include additional guidelines for specific
detailed areas of economic evaluation methodology, changes in the structure of
funding for pharmacoeconomic research, more education of consumers for
pharmacoeconomic data and more research partnerships between industry and its
customers.
PMID- 10182190
TI - The role of pharmacoeconomic evaluations in disease management.
AB - Disease management is a systematic approach to a health condition or a healthcare
intervention that organises preventative, interventional and care approaches
throughout the continuum of care and which measures outcomes in terms of
populations, not individuals. Disease management's advantage over the current
component system is that it stresses prevention over acute treatment of a chronic
disease. Patients with better control of their chronic diseases will likely have
a decrease in the use of emergency room and inpatient hospitalisation services,
thereby improving clinical outcomes of patients. To achieve these goals, disease
management uses pharmacoeconomic evaluations and outcomes measures to provide
information that helps build formularies and clinical practice guidelines.
Several problems exist in integrating pharmacoeconomic studies in disease
management models, such as the need for more integrated information systems,
standardisation and who should perform these evaluations. Some possible solutions
will be addressed in this article. With greater emphasis being placed on
controlling costs, the need for pharmacoeconomic evaluations in the design of
disease management models will continue to increase in the future.
PMID- 10182191
TI - 'The pros and cons of a single euro-price for drugs' and 'the economics of
parallel trade'.
PMID- 10182192
TI - The impact of managed care on clinical research.
AB - Traditionally, US teaching hospitals have subsidised research by charging higher
costs for treatment; however, this approach is being challenged. The growth of
managed-care organisations, concerned about maximising profits, has led many to
argue that clinical research will be damaged, whether by the loss of internal
funds for research or by reductions in the numbers of patients available for
studies. This review examines the evidence on which this argument is based. There
is some evidence that managed-care organisations are refusing to cover patients
who are involved in clinical trials, although, in general, they are receptive
towards research providing that it is explicit and seen as relevant. The indirect
effects of competition are, arguably, more important. Although many academic
centres have established strategies to protect research funds, those working in
the most competitive healthcare environments are obtaining fewer externally
funded research grants. They are also publishing fewer papers and are working in
climates that are seen as less supportive, with less ability to undertake
research that is not externally funded. There is little evidence that managed
care is reducing access to patients for clinical research. The growth of managed
care is, together with certain other trends, also influencing the nature of
clinical research. The overall consequences of these different factors are
difficult to predict, although there are grounds for concern about recruitment
and retention of junior researchers. The relationship between the various actors
involved in healthcare and research is dynamic and, as pressure is excerpted in a
particular direction, others adapt. It may be some time before the consequences
of policies being enacted now are apparent.
PMID- 10182194
TI - The economics of TRACE. A cost-effectiveness analysis of trandolapril in
postinfarction patients with left ventricular dysfunction.
AB - OBJECTIVE: The objective of the study was to compute a cost-effectiveness ratio
relating the economic cost of trandolapril to the number of effectiveness units
(i.e. life-years) gained. DESIGN AND SETTING: The trandolapril cardiac evaluation
(TRACE) study was a prospective placebo-controlled clinical trial designed to
determine the long term effect of the oral angiotensin-converting enzyme (ACE)
inhibitor trandolapril in postinfarction patients with left ventricular
dysfunction. We used the individual data of the TRACE trial to compute a cost
effectiveness ratio relating the economic cost of trandolapril to the number of
life-years saved. The analysis was differential and was conducted from a payer
perspective in a French setting. Costs were computed from individual data related
to the use of resources during the TRACE trial. For drug treatments, we chose
French public prices, and for hospitalisations, we used the mean cost as
determined by the diagnosis related group (DRG) from the 1996 Programme de
Medicalisation des Systemes d'Information (PMSI) database from the French
Ministry of Health. Life expectancy was estimated through an accelerated failure
time model with an exponential distribution specification; we made the
conservative hypothesis that the effect of trandolapril on mortality after the
end of the trial was nil. We assessed the standard deviation and the 95%
confidence interval (CI) of the ratio through its bootstrap distribution.
RESULTS: The incremental cost-effectiveness ratio of treating patients with
trandolapril rather than with placebo was estimated as 4910 French francs (FF)
per life-year saved. Discounting both costs and health effects led to ratio of
FF6950 per life-year saved. The bootstrap estimate of the ratio reached FF5950
and the 95% CI was FF5650 to FF6250 per life-year saved. CONCLUSIONS: These
results could be considered as highly cost effective, even though our estimation
was very close to the design and the conditions of the TRACE trial. Nevertheless,
we showed that this trial constitutes a favourable case for economic evaluation.
PMID- 10182193
TI - Cost effectiveness of coronary heart disease prevention strategies in adults.
AB - Although risk-factor modification has gained wide acceptance as an effective
approach to the prevention of coronary heart disease (CHD), health planners,
physicians and patients confront considerable uncertainty over the most
appropriate and efficient preventive strategies. Some preventive approaches are
both inexpensive and effective; others are expensive while their effectiveness is
slight or unproven. Effectiveness varies with an individual's age, gender and
other risk factors. Information provided by a cost-effectiveness analysis can
clarify the value of alternative strategies for CHD prevention in specific
populations, thereby helping to choose among them. It does so by producing a
standard measure of value--the cost per year of life saved (YLS) or cost per
quality-adjusted life-year (QALY) saved--that reveals which of several
alternative interventions provides the greatest health benefit from a given
expenditure. This article summarises the extensive literature on the cost
effectiveness of CHD prevention with an emphasis on primary prevention. Published
work indicates that smoking-cessation programmes, particularly those that rely on
counselling with or without nicotine supplements, are highly cost effective in
many settings. Although the evidence is limited, exercise programmes also appear
to be cost effective. The detection and treatment of hypertension is highly cost
effective, particularly when inexpensive drugs with proven effectiveness, such as
diuretics or beta-blockers, are used. Hormone-replacement therapy is a cost
effective approach to CHD prevention in most postmenopausal women, although
direct clinical trial data are lacking and it is uncertain which hormone
preparation is best. Cholesterol reduction is a cost-effective strategy for the
prevention of CHD in individuals without other treatable risk factors who are at
very high risk of developing CHD. For individuals with multiple CHD risk factors,
the choice of risk-modification strategies is complex and depends upon the
interactions of risk and the relative costs of treating each risk.
PMID- 10182196
TI - A new product pricing model using intracorporate market perceptions to extract
the value of additional information.
AB - OBJECTIVE: This model introduces a unique and inexpensive technique to estimate
profit increases that might be expected from: (i) an additional clinical trial to
establish a drug's second clinical indication; and (ii) a survey of market
demand. DESIGN: Microsoft Excel spreadsheets are used to solicit selected expert
opinions about the new product's annual market share under scenarios reflecting
different pricing points, promotional expenditures and clinical advantage. MAIN
OUTCOME MEASURES AND RESULTS: The preprogrammed model returns profit-maximising
price, promotional expenditure and market differentiation for each expert and the
group as a whole. The extent of disagreement among the experts is used to
estimate the additional profits which might be expected from a clinical trial and
a market survey. Results from an illustrative application indicated greater
incremental profits could be expected from the survey of market demand. The
clinical trial generated smaller expected incremental profits because several
experts felt that the trial's potential results would not affect the drug's
profit-maximising price. CONCLUSIONS: With a 1-day meeting between 6 experts, the
model provided a recommendation about the new product's profit-maximising market
price and promotional expenditure. Furthermore, it estimated profit increases
that might be expected from additional clinical trials and a survey of market
demand.
PMID- 10182195
TI - The cost of reaching National Cholesterol Education Program (NCEP) goals in
hypercholesterolaemic patients. A comparison of atorvastatin, simvastatin,
lovastatin and fluvastatin.
AB - OBJECTIVE: Recognising the importance of treating hyperlipidaemia, the National
Cholesterol Education Program (NCEP) has established widely accepted treatment
goals for low density lipoprotein cholesterol (LDL-C). Medications used most
commonly to achieve these LDL-C goals are HMG-CoA reductase inhibitors. The
relative resource utilisation and cost associated with the use of reductase
inhibitors of different LDL-C lowering efficacy are unknown, but are major health
and economic concerns. The objective of this study was to determine the mean
total cost of care to reach NCEP goals with various reductase inhibitors. DESIGN:
In a randomised, 54-week, 30-centre controlled trial we compared resources used
and costs associated with treating patients to achieve NCEP goals using 4
reductase inhibitors: atorvastatin, simvastatin, lovastatin and fluvastatin.
PATIENTS AND PARTICIPANTS: The trial studied 662 patients; 318 had known
atherosclerotic disease. INTERVENTIONS: Reductase inhibitor therapy was initiated
at recommended starting doses and increased according to NCEP guidelines and
package insert information. For patients who did not reach the goal at the
highest recommended dose of each reductase inhibitor, the resin colestipol was
added. MAIN OUTCOME MEASURES AND RESULTS: Patients treated with atorvastatin,
compared-with other reductase inhibitors, were more likely to reach NCEP goals
during treatment (p < 0.05), required fewer office visits (p < 0.001) and less
adjuvant colestipol therapy (p = 0.001). Consequently, the mean total cost of
care (1996 values) to reach NCEP goals was lower with atorvastatin [$US1064; 95%
confidence interval (CI): $US953 to $US1176] compared with simvastatin ($US1471,
95% CI: $US1304 to $US1648), lovastatin ($US1972; 95% CI: $US1758 to $US2186) and
fluvastatin ($US1542; 95% CI: $US1384 to $US1710). Results were similar for
patients with or without known atherosclerotic disease. CONCLUSIONS: In patients
requiring drug therapy for hypercholesterolaemia, NCEP LDL-C goals are achieved
significantly more often using fewer resources with atorvastatin compared with
simvastatin, lovastatin or fluvastatin.
PMID- 10182197
TI - The use of decision-analytical modelling in economic evaluation of patch testing
in allergic contact dermatitis.
AB - OBJECTIVE: The objective of this observational prospective study was to
demonstrate the cost effectiveness of patch testing in patients suspected of
allergic contact dermatitis (ACD) and to determine the order in which different
severity groups rank in terms of cost effectiveness. DESIGN AND SETTING: This
observational study was conducted on 567 patients from 10 investigator sites in
the US over a period of 1 year. All patients with a suspicion of contact allergy
who exhibited at least moderate disease activity were included in the study and
were stratified according to disease severity and whether or not they were patch
tested. In each severity category, the cost effectiveness of patch testing was
evaluated. Patients who were ruled out for contact allergy (without the use of
patch test) by the first 6 months after admission were excluded. A validated
dermatology-specific quality of life (DSQL) instrument was administered to all
patients at the start of the study, and at 6 and 12 months thereafter. The cost
effectiveness analysis is demonstrated using a decision-analytical model. Costs
included office visits and prescription costs without generic substitution. The
cost of patch testing was not included due to the large variation in price among
commercially available products. MAIN OUTCOME MEASURES AND RESULTS: Patch testing
was performed on 22% of patients with mild disease, 41% of patients with moderate
disease and 50% of those with severe disease. There was a significant difference
between the patch-tested and non-patch-tested groups in terms of the time to
obtain a confirmed diagnosis (medians = 8 and 175 days, respectively) and a
significant difference in the ratio of patients who had a confirmed diagnosis (88
and 69%, respectively). As a result of changes made in their lifestyle, 66% of
patients in the patch-tested group and 51% in the non-patch-tested group reported
75% or more improvement in their disease symptoms after 6 months. Early
confirmation of diagnosis helped reduce the prediagnosis cost of treatment which
was mostly based on preliminary diagnosis. The greatest quality-of-life (QOL)
benefits from patch testing relative to nonpatch testing occurred in patients
with recurrent/chronic ACD. CONCLUSIONS: Patch testing is most cost effective and
reduces the cost of therapy in patients with severe ACD. Greater improvements in
quality of life were seen in patients with recurrent/chronic ACD who were patch
tested than patients who were not patch tested within the same group. Results
were not sensitive to changes due to the addition of indirect costs or costs
using generic substitution.
PMID- 10182199
TI - Three-year follow-up of Drug Abuse Resistance Education (D.A.R.E.).
AB - The long-term effectiveness of D.A.R.E. was assessed by contrasting 9th-grade
students who received the program in the 6th grade with others who did not
receive the program. Of 38 elementary schools eligible for D.A.R.E. programs, 21
received the program and 17 did not. A follow-up survey assessed central D.A.R.E.
concepts such as self-esteem, resistance to peer pressure, delay of
experimentation with drugs, and drug use. Employing latent variables to represent
the concepts, no significant differences were found between D.A.R.E. participants
and controls. The authors discuss attenuation of effects and the generally
antidrug context of schools.
PMID- 10182200
TI - Violence against women. Examining ethnic differences and commonalities.
AB - Ethnic differences and commonalities rarely have been the focus of community
based research on violence against women. The few existing studies typically used
survey instruments developed on and used with Anglos and simply applied them to
members of other ethnic groups. The proposed conceptual framework is based on a
review of the published literature and on information gleaned from focus groups
conducted with women and men from four ethnic groups (Black, White, Asian, and
Latino). Ethnicity and culture--along with broad social factors and institutions,
gender role definitions, kin and friendship networks, and individual life-course
factors--influence what behaviors are acceptable in an intimate relationship. The
intersection of gender and ethnicity is hypothesized to influence the options
that a woman perceives, the help she seeks, and the nature and scope of violence
she experiences in an intimate relationship. Observations relevant to research,
policy, and service provision are offered.
PMID- 10182198
TI - Risperidone. A pharmacoeconomic review of its use in schizophrenia.
AB - The availability of new atypical antipsychotics, such as risperidone, that have
higher acquisition costs than conventional treatments has promoted
pharmacoeconomic evaluation of their costs and benefits. Risperidone is reported
to have superior efficacy to haloperidol and similar efficacy to other atypical
antipsychotics. At dosages < or = 8 mg/day, risperidone is generally associated
with a lower risk of extrapyramidal symptoms than conventional antipsychotics and
may have a more favourable effect on cognitive function and quality of life.
Overall treatment costs during the first year of risperidone treatment were lower
than in the previous year in a number of studies in patients with schizophrenia,
reflecting a reduction in hospitalisation, although costs slightly increased
after risperidone initiation in 2 studies. Total treatment costs were not
significantly different with risperidone or conventional antipsychotics in a
large, prospective naturalistic study. The use of risperidone in preference to
conventional antipsychotics in patients with chronic schizophrenia has been
supported by several modelled studies, including a cost-effectiveness analysis
that compared risperidone and haloperidol in chronic schizophrenia and a cost
utility study that compared the drug with oral haloperidol, depot haloperidol
decanoate and depot fluphenazine decanoate for 1 year's treatment of an initially
hospitalised chronic schizophrenic patient with moderate symptoms. In another
study, the cost-utility ratio for risperidone versus haloperidol was 24,250
Canadian dollars per quality-adjusted life year (year of costing not stated), but
only drug costs were considered. Risperidone had favourable cost-benefit ratios
relative to conventional antipsychotic treatment in a study that investigated a
scenario in which all patients hospitalised with newly diagnosed schizophrenia
received conventional antipsychotic therapy for 6 months, and then those who did
not respond received a 6-month trial of risperidone or clozapine. The results of
2 limited decision-analytical models did not favour risperidone. One study
compared risperidone with oral haloperidol or depot haloperidol decanoate for the
outpatient treatment of a schizophrenic patient with a history of relapse and
rehospitalisation. The other compared risperidone, olanzapine and oral
haloperidol for the treatment of schizophrenia. CONCLUSIONS: Despite its high
acquisition cost, risperidone does not increase, and may even reduce, overall
treatment costs of schizophrenia by reducing hospitalisation compared with
standard treatment regimens. While further pharmacoeconomic evaluation of
risperidone as a first-line agent is required, pharmacoeconomic data overall
support its use in patients with chronic schizophrenia.
PMID- 10182201
TI - Mandatory seat belt laws in the states. A study of fatal and severe occupant
injuries.
AB - This study examines the impact of mandatory seat belt laws on fatal and
incapacitating injury rates in the states. Annual data for all 50 states for the
period 1975-1991 are used. Pooled time series analysis is employed. The general
conclusion that emerges from this analysis is that seat belt laws significantly
impact state fatal injury rates. Primary enforcement and all-seat coverage
provisions appear to be particularly effective in reducing fatality rates.
PMID- 10182202
TI - Estimating the cost impact of three dual diagnosis treatment programs.
AB - Specialized intervention programs for people with concurrent severe mental
illness and substance abuse reduce the total costs of care. Compared to baseline,
cost savings of over 40% were achieved by 18 months, primarily due to significant
reductions in the use of acute and subacute mental health services and despite an
increase in outpatient mental health services. There also was an observable
impact on cost reductions in medical and criminal justice services without an
increase in family costs over the same time period.
PMID- 10182203
TI - More appropriate evaluation methods for community-level health interventions.
Introduction to the special issue.
PMID- 10182204
TI - Batch sampling to improve power in a community trial. Experience from the
Pawtucket Heart Health Program.
AB - Experiments involving large social units, such as schools, work sites, or whole
cities, are commonly limited in statistical power because the number of
randomized units is small, leaving few degrees of freedom for residual (between
unit) error. The authors describe a method for increasing residual degrees of
freedom in a community experiment without substantially increasing cost or
difficulty. In brief, they propose that the experimental units should be divided
into random subsamples (batches). Batch sampling can improve statistical power if
the community endpoint means are stable over time or if their temporal variation
is comparable in period to the batch-sampling schedule. The authors demonstrate
the theoretical advantages of the batch system and illustrate its use with data
from the Pawtucket Heart Health Program, in which such a design was implemented.
PMID- 10182205
TI - A strategy for accurate collection of incremental cost data for cost
effectiveness analyses in field trials. Pawtucket's minimal contact cholesterol
education intervention.
AB - With many community field trials or education interventions, the cost
effectiveness analyses are not given a high priority. However, this type of
evaluation is important for purposes of future adoption of the intervention. The
accurate measurement of costs can best be served by prospective collection of
data. This article describes a methodology for collection of cost data that
coincides with the intervention implementation. This cost analysis strategy has
seven discrete steps. The Minimal Contact Education for Cholesterol Change study
is used as an example of the use of this strategy. This intervention provides
cholesterol education at six different levels of intensity at four different
sectors. The intensity levels vary along a continuum from very little education
input to a maximum level of intervention that might be practical in a screening
setting. The cost-effectiveness analysis component of the study will identify the
incremental cost-effectiveness of each intervention along the continuum.
PMID- 10182206
TI - Using process data to explain outcomes. An illustration from the Child and
Adolescent Trial for Cardiovascular Health (CATCH).
AB - The purpose of this article is to illustrate the use of process evaluation for
understanding study outcomes. Data from the Child and Adolescent Trial for
Cardiovascular Health (CATCH), a large school-based field trial, are used.
Teacher characteristics, measures of classroom curriculum implementation, and
competing influences are linked to changes in dietary knowledge, intentions, and
self-efficacy of students in the intervention schools. Multiple regression
analyses indicate that teacher characteristics did not predict program
implementation. Teacher characteristics and program fidelity, or the number of
modifications made to the classroom curriculum during implementation, had direct
and independent effects on student outcomes.
PMID- 10182207
TI - A Monte Carlo study of alternative responses to intraclass correlation in
community trials. Is it ever possible to avoid Cornfield's penalties?
AB - Strategies to avoid the penalties of extra variation and reduced degrees of
freedom in community trials were compared in Monte Carlo simulations. Three
conditions were found necessary to ensure nominal Type I and II error rates: (a)
Condition variation must be assessed against assignment unit variation, (b) the
critical value for the test statistic must be based on the assignment unit
degrees of freedom, and (c) estimation of negative intraclass correlations must
be allowed in the analysis. Using other test statistics and other degrees of
freedom, and fixing negative intraclass correlations at zero often gave Type I
and II error rates far from their nominal levels.
PMID- 10182208
TI - Gauss or Bernoulli? A Monte Carlo comparison of the performance of the linear
mixed-model and the logistic mixed-model analyses in simulated community trials
with a dichotomous outcome variable at the individual level.
AB - This Monte Carlo study compares performance of the linear and the logistic mixed
model analyses of simulated community trials having event rates of 37%, 13%, or
5%, intraclass correlations between 0.01 and 0.05, and 17 or 5 denominator
degrees of freedom. Type I or Type II error rates showed no essential difference
between the two analysis methods. They showed depressed error rates when the
event rate or the denominator degrees of freedom were small. The authors conclude
that in studies with adequate denominator degrees of freedom, the researcher may
use either method of analysis but should accept negative estimates of components
of variance to avoid depression of error rates.
PMID- 10182209
TI - Preventive ethics, managed practice, and the hospital ethics committee as a
resource for physician executives.
PMID- 10182210
TI - The healthcare ethics committee in the structural transformation of health care:
administrative and organization ethics in changing times.
PMID- 10182211
TI - An ethics discussion series for hospital administrators.
PMID- 10182212
TI - Catholic sponsorship and Medicare managed care: an uneasy alliance of faith and
market.
PMID- 10182213
TI - An HMO grievance committee: ethical challenges and opportunities for the
organization.
PMID- 10182214
TI - Expanding into organizational ethics: the experience of one clinical ethics
committee.
PMID- 10182215
TI - Adoption, reproductive technologies, and genetic information.
PMID- 10182216
TI - Lost in a doctrinal wasteland: the exceptionalism of doctor-patient speech within
the Rehnquist Court's First Amendment jurisprudence.
PMID- 10182217
TI - DNA blueprints, personhood, and genetic privacy.
PMID- 10182218
TI - Health care information and privacy.
PMID- 10182219
TI - Internet psychotherapy: current status and future regulation.
PMID- 10182221
TI - Black Sunday for FPA.
PMID- 10182220
TI - The PSO bandwagon.
AB - In summary, if an organization is thinking of putting together a PSO they should
do a thorough due diligence with a focus on their physician interest and
competencies. The feasibility needs to be realistic. Some physician organizations
we've talked with aren't even considering a PSO. They have too many other fish to
fry. Not only that, there is a natural reluctance to dive into a pool without a
bottom. Medicare can be counted on to keep changing the rules. Without a set of
rules you can count on, why should you engage in the game? It's facinating to
watch HCFA staff engaged in their intramural, camp-fire deliberations. They sit
around in a circle and ask "what if?" If we reward providers for taking care of
sick people, will they simply recruit more sick people? Think about that question
for a minute. Isn't there something twisted in this? To be sure, a PSO is not for
the naive or faint of heart. To be realistic, budget a minimum of 3 years to
break even. If you decide to go ahead with a PSO, the tuition you pay today for
the learning curve should benefit you in the years to come. Plan for the best.
Prepare for the worst. With opportunity comes risk. Find a visionary to lead this
new venture. Only those who see the invisible, can do the impossible.
PMID- 10182222
TI - High ideals & perverse consequences: risk adjustments, encounter data &
Medicare+Choice.
AB - Why should you take on the risks and complications of developing a PSO? Is it
worth it? Will it mean assuming undue risk? The answer to this question gets
complicated. This article will introduce more uncertainties than you had before.
But, you need to have your eyes wide open. It's not just a question of your
capability as a health system or a medical group. It's a question of HCFA's
ability to administer the program. Even without knowing the capabilities of HCFA,
most organizations would say that they don't trust the government to follow
through with any program. In this article by Bruce Fried, we get a rare look at
the inner thoughts and gyrations of government, as they attempt to risk-adjust
Medicare payments to PSOs and HMOs. In ordinary language, that means, if you
happen to have a very sick population of seniors, you will be paid more to take
care of them. But, read this and weep.
PMID- 10182223
TI - Sobering up about AIDS.
PMID- 10182224
TI - Frontier medicine. How to find the right doctor for alternative care.
PMID- 10182225
TI - Is AIDS forever?
PMID- 10182226
TI - A mysterious baby mix-up.
PMID- 10182227
TI - HCFA delays consolidated billing requirements for Non-PPS SNFs until further
notice.
PMID- 10182228
TI - MedPAC urges careful oversight of post acute care providers.
PMID- 10182229
TI - New provider reimbursement manual offers clarifications on PPS but also raises
new questions.
PMID- 10182230
TI - Lawmakers press for stepped up oversight of nursing facilities.
PMID- 10182231
TI - HCFA clarifies how therapies are coded on the MDS (minimum data set).
PMID- 10182232
TI - HCFA makes day of admission as day one for both PPS, RAI (resident assessment
instrument).
PMID- 10182233
TI - The next step in managed care contracting: calculating your capitation rate.
PMID- 10182234
TI - Practice or medical management: which key to success?
AB - In the past, practice management systems were considered most important. Since
revenues were based on fees for services rendered, the more patients and
particularly procedures that could be scheduled in a day, the greater one's
income. However, medical management systems are essential for the financial
success of HMOs; these functions must also be present for the capitated group
practice to be successful.
PMID- 10182235
TI - Stats & facts. Learning from consumer satisfaction surveys.
PMID- 10182236
TI - What does accreditation mean for PPOs?
AB - In the early years of managed care, a buyer's selection process was dictated by
price. As quality becomes a greater issue in managed care, the need for usable
standards for the entire managed care industry becomes evident. The work of
accrediting bodies provides a reference for buyers to discern quality
organizations in the industry. This article stresses the need for company
commitment during the accreditation process and the benefits that can be derived
from consumer/industry awareness and government regulation.
PMID- 10182237
TI - Life-long learning for professional satisfaction.
PMID- 10182238
TI - Pharmacy student expectations for professional practice.
AB - The professional employment market for pharmacists has changed radically in
recent years. Additionally, data regarding perception of future practice among
pharmacy students are limited. The purpose of this study was to characterize
expectations for professional practice among pharmacy students and to identify
curriculum support at a college of pharmacy. A survey examining student
educational experiences, career preferences, and demographic variables was
distributed to 1,297 students enrolled in the first to sixth year. Six hundred
thirty responses were evaluated. Doctor of Pharmacy students indicated that their
education better prepared them for their expected career than did Bachelor of
Science students (P < .03). The former also had a more positive outlook regarding
future career opportunities than the latter (P < .01) and indicated to a greater
extent that HMOs and pharmacy benefit management companies are growing sources of
employment for pharmacists (P < .001).
PMID- 10182239
TI - Patient empowerment in disease state management programs.
PMID- 10182240
TI - Medication nonadherence--Part I: The health and humanistic consequences.
AB - Nonadherence is a significant medical problem in the United States, leading to
excessive morbidity, mortality, and medical costs. In this first installment of a
two-part article, the authors review the literature and discuss the effects of
the problem, with particular reference to patients with congestive heart failure.
PMID- 10182241
TI - Design and implementation of genetic services within an HMO.
AB - Clinical application of genetic knowledge is essential for providing effective
preventive health care. A large HMO such as Kaiser Permanente is an ideal setting
for this application. Implementing a comprehensive program for genetic screening
is complex, however, and requires informed consent, laboratory testing, test
interpretation, genetic counseling, follow-up for positive screening results, and
database systems. This article summarizes genetic services provided by Kaiser
Permanente at four subregional genetic centers in Northern California.
PMID- 10182242
TI - Health care insolvency and bankruptcy.
AB - Bankruptcy is an event that is often considered a business' worst nightmare.
Debt, lawyers, and the U.S. government can lead to the eventual destruction of a
business. This article shows how declaring bankruptcy can be a helpful instrument
in continuing a successful venture in the health care marketplace.
PMID- 10182243
TI - Marketplace. How branding improves bottom line: learning from HealthSouth's
strategy.
PMID- 10182244
TI - Perspectives. Haste makes waste in states' managed behavioral care efforts.
PMID- 10182245
TI - The French reforms: a rich area for health services research.
PMID- 10182246
TI - Women and disability.
PMID- 10182247
TI - Aggregating health state valuations: a reply to Erik Nord's comment.
PMID- 10182248
TI - Implementing quality: a study of the adoption and implementation of quality
standards in the contracting process in a general practitioner multifund.
AB - The increase in managerialism in the 1980s and the 1990 NHS reforms have had
major implications for the regulation of providers. Purchasers of health care in
the UK are now expected to specify three factors in their contracts: volume, cost
and quality. This paper focuses on one of these: i.e. the quality standards
purchasers now include within their health service contracts. The case study is
of a general practitioner multifund and the analysis focuses on how quality
standards are derived and adopted in outpatient contracts. The data were derived
from in-depth face-to-face interviews with the key participants in the
contracting process. The evidence shows that the standards were derived and
adopted with very little participation from the providers. The impact of the
quality standards on hospitals consultants' behaviour was negligible, there was
very little monitoring of the standards by the multifund, and providers accepted
standards which they knew they could not meet. It is concluded that this non
participatory method of developing the quality standards is likely to mean that
their impact on service delivery will be limited.
PMID- 10182249
TI - Distributional dilemmas in health policy: large benefits for a few or smaller
benefits for many?
AB - OBJECTIVES: To examine funding priorities assigned by health ministry officials
when choosing between clinical programs that offer similar overall benefits
distributed in different ways (e.g. large gains for a few versus small gains for
many), and to compare the relative magnitude of any distributional bias to age
biases. METHODS: A survey consisting of paired hypothetical health care programs
was mailed to the 135 most senior officials of the Health Ministry in Ontario,
Canada (population 11.5 million). Respondents were asked to assume they were
members of a panel allocating a fixed sum of money to one of two programs in each
pair. All program descriptions included the number of persons affected each year
by a given disease and the average survival gains from the hypothetical programs.
Some scenarios also mentioned the side-effects associated with programs and/or
the average age of the beneficiaries. RESULTS: Four respondents had retired/died.
Of 131 eligible respondents, 80/131 (61%) provided usable responses. Asked to
choose between providing large benefits to a few citizens and small benefits to a
great many, 23% (95% CI: 14%, 33%) of respondents were unable to decide, but
55.8% (95% CI: 47%, 70%) favored providing large benefits to fewer patients.
Eliminating the 23% unable to decide, 47/62 or 76% (CI 63%, 86% expressed a
distributional preference. With a smaller distributional discrepancy, indecision
increased, with 35% of respondents having no preference and the remainder split
almost evenly between the two programs. Other scenarios showed that health
officials' pro-youth biases were only slightly larger than their distributional
preferences and that distributional preferences were magnified when combined with
minor differences in average ages of beneficiaries. CONCLUSIONS: A substantial
minority of health care decision-makers had difficulty choosing between programs
with similar overall gains and distributional differences--a result consistent
with the utilitarian assumptions of cost-effectiveness analysis. However, when
distributional differences were large, decision-makers clearly favored large
gains for a few beneficiaries rather than small gains for many. Policy analysts
should explicitly weigh distributional issues along with aggregate health gains
when addressing resources allocation problems.
PMID- 10182250
TI - Variation in hospital use and avoidable patient morbidity.
AB - OBJECTIVES: To determine whether geographical areas with relatively low overall
hospitalization rates have higher population-based rates of admission of patients
with advanced stages of disease. METHODS: Age- and sex-standardized hospital
admission rate were calculated for the residents of the 80 Local Health Units in
Lombardia, Italy. Using the Disease Staging classification, advanced stage
admissions were identified for six common medical and surgical conditions, which
it was presumed would reflect untimely hospital admission. Standardized rates of
advanced stage admissions were compared in areas with overall high
hospitalization rates (high-use areas). RESULTS: Hospitalization at advanced
stages of disease in the low-use areas were significantly higher for the six
conditions combined (55.9 vs 43.0 per 100,000; P = 0.005), and for external
hernia, appendicitis and uterine fibroma, but not for bacterial pneumonia,
diverticular disease and peptic ulcer. For the six study conditions combined,
residents of overall low-use area were 30% more likely to be admitted with
advanced stages of disease. CONCLUSION: Low overall hospitalization rates were
found to be associated with greater severity of illness at hospitalization and
potentially avoidable morbidity for some conditions. Policies aimed at curbing
unnecessary hospital admission should consider preserving access for appropriate
treatment.
PMID- 10182251
TI - Medical necessity, benefit and resource allocation in health care.
AB - Many health care systems espouse medical necessity, or need, as a guiding
principle for the allocation of resources. Yet, logic and experience suggest that
it is likely impossible to develop a concise, explicit, operational definition of
medical necessity that would allow it to be used as an administrative or
management tool. Even if such a definition could be developed, it would likely do
little to solve the fundamental challenges facing policy-makers attempting to
reform health care systems. This implies that we should refrain from further
efforts to define medical necessity operationally. But does it follow that
medical necessity is an empty concept? No. Even if it cannot be defined
precisely, it can still serve as a guiding principle for health policy. Given
that ability-to-benefit is a core concept underlying necessity, we develop a
conceptual framework that encompasses alternative notions of benefit and then
illustrate some selected implications of alternative benefit notions for
processes required to use medical necessity as a guiding principle and for the
types of services that would be deemed to produce a benefit.
PMID- 10182252
TI - Strategies for the management of hypercholesterolaemia: a systematic review of
the cost-effectiveness literature.
AB - OBJECTIVE: To review research addressing the management of cholesterol in the
prevention of coronary heart disease in order to assess the cost-effectiveness of
such interventions. METHODS: A systematic review of economic evaluations
identified through searches of MEDLINE and the Social Sciences Citation Index
revealed 38 studies addressing the cost-effectiveness of cholesterol management.
They were distinguished according to screening approaches, dietary advice and
drug treatment. Most studies were not associated directly with clinical trial
results, but adopted economic modelling approaches. RESULTS: Whilst there is
general agreement among the majority of analyses, studies of cholesterol
management concerned with screening strategies were extremely sensitive to
changes in their assumptions; so much so that only a limited emphasis may be
placed on specific cost-effectiveness ratios and the conclusions drawn from them.
All studies considered direct costs, though many were limited to drug costs. The
cost-effectiveness of primary prevention by cholesterol-lowering drugs is highly
variable, depending on age at initiation of treatment and cardiovascular risk
profile. Pharmacological intervention is least cost-effective in the young and
the elderly. The cost-effectiveness of cholesterol-reducing agents improves when
they are targeted at those at high risk. HMG-CoA reductase inhibitors are
generally more effective and more cost-effective at reducing cholesterol-related
coronary events than other medications. CONCLUSION: The methods and economic data
upon which these studies are based need to be improved if robust policy
conclusions are to be formulated.
PMID- 10182253
TI - Evidence-based health care: management and practice.
PMID- 10182254
TI - Confidence intervals for cost-effectiveness ratios: the use of 'bootstrapping'.
PMID- 10182255
TI - Beyond ethnic categories: why racism should be a variable in health services
research.
AB - Racism can affect health by making people ill, exacerbating existing illness, and
by inequality in access to and utilisation of health services. Recent British
publications assessing the methods used in studies of ethnicity primarily
considered the status of the variables 'ethnicity' and 'race' and advised on the
use of appropriate categories. Such scrutiny of ethnicity research is welcomed,
yet authors rarely emphasise the importance of racism as a variable. This paper
discusses why racism matters as a variable and poses suggestions for its absence
from British health services research. Reference is made to US research to
demonstrate that this focus is important and feasible. Health services research
that considers ethnicity and excludes the effect of racism may result, at best,
in an incomplete understanding. At worst, this omission could itself be perceived
as a racist practice.
PMID- 10182256
TI - Do-it-yourself disease management programs.
PMID- 10182257
TI - A nursing-based best practice network.
PMID- 10182258
TI - Putting primary care guidelines into practice.
PMID- 10182259
TI - Intranet application has all the right stuff for guideline development.
PMID- 10182260
TI - Vermont program targets a few key interventions.
PMID- 10182261
TI - Build an evidence-based CAD (coronary artery disease) prevention program.
PMID- 10182262
TI - A primer on Internet-based patient education.
PMID- 10182263
TI - Advising physicians how to choose a strategic partner.
PMID- 10182264
TI - Healthcare joint ventures.
PMID- 10182266
TI - Medical waste update.
PMID- 10182265
TI - When worlds collide: elder caregiving poses new challenges for balancing work and
life.
AB - Nearly one in four U.S. households (an estimated 22.4 million) are caring for
elderly family members or friends; as the nation's population ages, more and more
workers will take on elder caregiving responsibilities. As this trend continues,
employers will face increasing concerns about lost productivity and many
employees will struggle to balance the demands of work and caregiving
responsibilities. To help resolve the situation, many employers may look to a
comprehensive work/life program, which incorporates an intensive focus on elder
care issues, to help boost morale, improve employee productivity and job
performance, and reduce stress and absenteeism associated with caregiving.
PMID- 10182267
TI - Medical equipment cleaning moves toward automation.
PMID- 10182268
TI - Team cleaning in a healthcare setting.
PMID- 10182269
TI - Technologies and systems for the future of medical waste management.
PMID- 10182270
TI - Data trends. Key organizational performance indicators.
PMID- 10182271
TI - Top 10 Medicare DRGs as a percentage of total Medicare DRG payment.
PMID- 10182272
TI - It's health care, stupid!
PMID- 10182273
TI - Mergers in health care: avoiding divorce IDS style.
AB - The recent flurry of merger activity in the healthcare industry has given rise to
a significant number of integration efforts. Unfortunately, some of these
"marriages" will end in "divorce." Reasons for failure can be found in four
critical dimensions of integration: structural, operational, clinical, and
informational. Each dimension has its associated pitfalls, and every merger
confronts clearly identifiable risks. By taking steps to mitigate such risks,
merging organizations can improve the chances the merger will succeed. If the
merger does fail, measures taken prior to the merger, such as including an escape
clause in the merger contract, can help avoid problems in dividing operational
assets, physicians practices, and information assets.
PMID- 10182274
TI - Improving the financial performance of IDS-owned physician practices.
AB - Although physician practices acquired by integrated delivery systems (IDSs) have
tended to show financial losses, these practices still offer IDSs considerable
overall benefits, such as expanded market share and greater coordination of care.
IDSs should not necessarily avoid acquiring practices. However, it is essential
that IDSs take steps to improve the financial performance of acquired practices.
PMID- 10182275
TI - Beyond HMOs: trends in employer direct contracting.
AB - The California Public Employees' Retirement System (CalPERS) is exploring the
possibility of contracting directly with providers to furnish healthcare services
to its members. This move may signal a trend among employers to pursue direct
contracting opportunities. The direct-contracting experience of Minnesota's
Buyers Health Care Action Group (BHCAG) high-lights how such arrangements may be
structured. Direct contracting may not yet exist in every market. Nonetheless,
providers that proactively position themselves to meet employer expectations
should be able to strengthen their market position and gain leverage in
contracting with managed care organizations.
PMID- 10182276
TI - Telephone triage improves demand management effectiveness.
AB - Telephone triage, or telephone advice counseling, is becoming a key managed care
point-of-entry tool for patients and health plan members accessing the health
system. Telephone triage functions as a logical front-end for health plans,
integrated physician groups, or integrated delivery systems that want to shift
their managed care efforts toward demand management. Key components of telephone
triage include patient education, patient information, and guided access to
appropriate care. Telephone triage generally requires 24-hour staffing by
registered nurses and a computer software package based on either clinical
protocols or clinical algorithms. Organizations can either install an in-house
system or purchase this service from a vendor, health plan, or another provider.
The decision to develop a telephone triage service in-house or to out-source it
is determined largely by volume and the user's strategy for moving to successive
levels of risk management.
PMID- 10182277
TI - Laboratory reengineering facilitates cost management.
AB - In 1993, The Medical University of South Carolina (MUSC) in Charleston undertook
a change management initiative to achieve a more cost-competitive position in its
market and become a more attractive partner for a possible future affiliation
with another provider organization. A key element of this change process was a
reorganization of the medical center's laboratory department. Through
consolidation of MUSC's separate laboratories and the introduction of a new, more
efficient chemistry analyzer system, the medical center realized annual
laboratory savings of approximately $1.3 million.
PMID- 10182278
TI - Two-part transfer pricing improves IDS financial control.
AB - To help coordinate patient care services across its various provider entities, an
integrated delivery system (IDS) must address two financial control matters:
design of responsibility centers and selection of an appropriate transfer pricing
methodology. Although designating an HMO as a profit center is appropriate, such
a designation is inappropriate for an IDS's provider entities. Instead, these
entities are more appropriately designated as standard expense centers. Further,
an HMO owned and operated by an IDS should purchase patient care from the
delivery entities by means of two-part transfer prices, that is, having fixed
costs paid for in a lump sum and variable costs paid for on the basis of the
actual volume and mix of services provided. The IDS's management must recognize,
however, that both case mix and volume lie largely outside a hospital's control
and that financial controls should focus on a combination of the hospital's fixed
costs and variable costs associated with resources per case, efficiency of
resource delivery, and factor prices.
PMID- 10182279
TI - Measuring atypical activity in hospital claims data.
PMID- 10182280
TI - Activity-based analyses lead to better decision making.
AB - Activity-based costing (ABC) and activity-based management (ABM) are cost
management tools that are relatively new to the healthcare industry. ABC is used
for strategic decision making. It assesses the costs associated with specific
activities and resources and links those costs to specific internal and external
customers of the healthcare enterprise (e.g., patients, service lines, and
physician groups) to determine the costs associated with each customer. This cost
information then can be adjusted to account for anticipated changes and to
predict future costs. ABM, on the other hand, supports operations by focusing on
the causes of costs and how costs can be reduced. It assesses cost drivers that
directly affect the cost of a product or service, and uses performance measures
to evaluate the financial or nonfinancial benefit an activity provides. By
identifying each cost driver and assessing the value the element adds to the
healthcare enterprise, ABM provides a basis for selecting areas that can be
changed to reduce costs.
PMID- 10182281
TI - Increasing the marketability and recognition of provider network joint ventures.
AB - Physicians have been developing provider network joint ventures to market their
services jointly to managed care plans, employers, and other purchasers. Over the
past few years, external market factors have produced a growing impact on these
joint ventures. These external market factors include the Federal government's
revised antitrust guidelines, National Committee for Quality Assurance
activities, and state and Federal consumer protection laws. Simply responding to
these forces may not increase a provider network's marketability unless the
network can demonstrate its value in the terms and measurements accepted by the
consumer, managed care plans, and provider networks. By doing so, a provider
network can not only increase its marketability, but also increase its
recognition in the market, improve its competitive advantage, and enhance its
return on investment.
PMID- 10182282
TI - Market dominance of PHO entities is key to achieving PHO success.
AB - Hospital-physician integration alone will not help providers achieve the leverage
and/or cost structure necessary to succeed under managed care. Hospitals first
need to gain institutional dominance in their markets, facilitate the
consolidation of physician groups, and create fair hospital-physician
partnerships.
PMID- 10182283
TI - EDI and document imaging can work together.
PMID- 10182284
TI - HCFA proposes using physician fee schedule to pay for outpatient rehabilitation.
PMID- 10182285
TI - Combining funds to achieve investment efficiency.
PMID- 10182286
TI - Buildings. Concrete issues.
PMID- 10182287
TI - Telephone helplines. Direct enquiries.
AB - A survey of potential users of NHS Direct showed the idea was popular,
particularly with parents of children under five, people with long-term illness
and carers. Respondents envisaged the main function of the service as providing
advice on minor ailments. Most respondents were willing to pay for a local call
to ring the service.
PMID- 10182288
TI - General practice. Omission to explain.
PMID- 10182289
TI - Occupational health. Saying it with flowers.
PMID- 10182290
TI - Hospitals. Trauma without crisis.
AB - Reorganising orthopaedic consultant rotas to ensure that each week one consultant
undertakes five dedicated trauma sessions has resulted in significant
improvements. The changes have reduced the average length of stay by two days,
reduced walts for first appointments in the fracture clinic to within 24 hours
and yielded potential savings of almost 350,000 Pounds a year at a time when
admissions are rising by 18 per cent a year. The project involved massive
cultural change and took 18 months from inception to review to ensure the support
and involvement of consultants and other staff.
PMID- 10182291
TI - Independent sector. A breath of fresh air.
PMID- 10182292
TI - Data briefing. Health spending.
PMID- 10182293
TI - Can primary care and community-based models of emergency care substitute for the
hospital accident and emergency (A & E) department?
AB - This systematic review assesses the extent to which primary-secondary
substitution is possible in the field of emergency care where the range of
options for the delivery of care is increasing in the UK and elsewhere. Thirty
four studies were located which met the review inclusion criteria, covering a
range of interventions. This evidence suggested that broadening access to primary
care and introducing user charges or other barriers to the hospital accident and
emergency (A & E) department can reduce demand for expensive secondary care,
although the relative cost-effectiveness of these interventions remains unclear.
On a smaller scale, employing primary care professionals in the hospital A & E
department to treat patients attending with minor illness or injury seems to be a
cost-effective method of substituting primary for secondary care resources.
Interventions that addressed both sides of the primary-secondary interface and
recognised the importance of patient preferences in the largely demand-driven
emergency service were more likely to succeed in complementing rather than
duplicating existing services. The evidence on other interventions such as
telephone triage, minor injuries units and general practitioner out of hours co
operatives was sparse despite the fact that these interventions are growing
rapidly in the UK. Quantifying the scope for substitution in any one health
system is difficult since the evidence comes from international research studies
undertaken in a variety of very different health settings. Simply transferring
interventions which succeed in one setting without understanding the underlying
process of change is likely to result in unexpected consequences locally.
Nevertheless, the review findings clearly demonstrate that shifting the balance
of care is possible. It also highlights a persistent gap in professional and lay
perceptions of appropriate sources of care for minor illness and injury.
PMID- 10182294
TI - Economic evaluation of end stage renal disease treatment.
AB - This paper examines the cost-effectiveness of end stage renal disease (ESRD)
treatments. Empirical data on costs of treatment modalities and quality of life
of patients were gathered alongside a clinical trial and combined with data on
patient and technique survival from the Dutch Renal Replacement Registry. A
Markov-chain model, based on the actual Dutch ESRD program as of January 1st
1997, predicted the cost-effectiveness and cost-utility of dialysis and
transplantation over the 5-year period 1997-2001. Total annual costs amounted to
DFL 650 million (1.1% of the health care budget). Centre Haemodialysis was found
to be the least cost-effective treatment, while transplantation and Continuous
Ambulatory Peritoneal Dialysis (CAPD) were the most cost-effective treatments.
The Markov-chain model was used to study the influence of substitutive policies
on the overall cost-effectiveness of the ESRD treatment program. The influence of
such policies was found to be modest in the Dutch context, where a high
percentage of patients is already being treated with more cost-effective
treatment modalities. In countries where Centre Haemodialysis is still the only
or the major treatment option for ESRD patients, substitutive policies might have
a more substantial impact on cost-effectiveness of ESRD treatment.
PMID- 10182295
TI - Primary health care meets the market in China and Vietnam.
AB - China and Vietnam developed low cost rural health services between the 1950s and
the mid-1970s. These services contributed to substantial improvements in health.
Both countries have been liberalising their economies for a number of years.
Partly as a result of these changes health facilities have become increasingly
dependent on user charges, and they have gained considerable independence from
political or bureaucratic control. There has also been a growth in private
provision. This has given people a wider choice of health services, but costs
have risen and there are greater differences in access to medical care. The
Chinese and Vietnamese governments face fundamental questions about the future
development of the health sector.
PMID- 10182296
TI - What is Germany's experience on reference based drug pricing and the etiology of
adverse health outcomes or substitution?
AB - Germany is frequently cited as an example of reference based pricing (RBP) in
ongoing controversial discussions on the effect of RBP. There are thorough
analyses of phase I and II RBP on Germany's drug market. However, any conclusions
on the overall economic and public health impact of RBP, solely on the basis of
aggregated data, must be suspect to substantial bias, since too many factors in a
rapidly changing health care system remained uncontrolled. Parallel to the
introduction of phase II RBP in 1992/1993, the second health care reform became
active. The two major confounding factors were the introduction of fixed drug
budgets and the many changes due to the unification of Germany that took place in
the beginning of the 1990s. Published and unpublished aggregated data do not
allow any conclusions on the etiology of adverse health events due to this change
in drug reimbursement policy. Conclusions drawn from the German experience will
be based on assumptions or speculations that are hard to prove. A health care
system that identifies enough evidence and need to introduce RBP as a measure of
cost control should make every effort to evaluate the effects in order to
increase program compliance or, if indicated, make adaptations to the RBP policy.
The introduction of RBP in British Columbia in 1995-1997 and its computerized
administrative health databases covering a large proportion of the population
should give rise to a thorough analysis of this policy.
PMID- 10182297
TI - Modernisation of the system of traditional Korean medicine (1876-1990).
AB - For the past two centuries or so, the emergence and growth of scientific medicine
has resulted in the gradual replacement non-scientific medical practitioners with
scientific medical practitioners at the field of public health in most Western
countries. The key factor behind this transformation has been the official policy
that has encouraged practitioners of scientific medicine while at the same time
suppressing and ignoring practitioners of non-scientific medicine. The case of
the Republic of Korea (henceforth called Korea) reveals, however, a small
discrepancy from this general trend, i.e. the coexistence of practitioners of
both non-scientific medicine and scientific medicine. This article explores the
modernisation of the system of Traditional Korean Medicine from 1876 to 1990 in
an attempt to answer why the Korean health care system has a dual system of
medical care and argues that the dual system of medical care in Korea was shaped
by the conflicts and tensions between herbal doctors and Western trained doctors
throughout the various stages of historical development.
PMID- 10182299
TI - First winners of Ernest A. Codman Award named.
PMID- 10182298
TI - Quality oversight bodies coordinate measurement activities.
PMID- 10182300
TI - Update on ORYX: the next evolution in accreditation.
PMID- 10182301
TI - 1998 random unannounced survey topics announced.
PMID- 10182302
TI - Implementation of laptops continues in 1998.
PMID- 10182303
TI - 1997 Accreditation Manual for Preferred Provider Organization. Leadership and
Management of Human Resources chapters. Joint Commission on Accreditation of
Healthcare Organizations.
PMID- 10182304
TI - Year 2000 computing issue: preparing for the millennium.
PMID- 10182306
TI - Special report--restraint and seclusion standards.
PMID- 10182305
TI - Challenging ambulatory care standards: tips for better compliance.
PMID- 10182307
TI - Survey Postponement Policy revised.
PMID- 10182308
TI - Both sides win. Deal to pay off for Columbia and not-for-profit group.
AB - While the nation's largest for-profit chain retrenches, members of a not-for
profit healthcare consortium are barreling ahead to solidify their market
positions. Columbia/HCA Healthcare Corp. and the eight-member buying group last
week disclosed details of an agreement that will result in the sale of 22
hospitals in Columbia's 45-hospital Atlantic Group. The consortium will pay $1.2
billion in cash.
PMID- 10182309
TI - Singing the Blues. Plans lost big on operations in '97; enrollment unscathed.
PMID- 10182310
TI - Standardizing standards. Accrediting agencies form council to end confusion.
PMID- 10182311
TI - Call for common sense. Hospitals rethink policies after ER denies dying boy care.
PMID- 10182312
TI - JCAHO surveys Ravenswood.
PMID- 10182314
TI - Special report: Multi-unit Providers Survey.
PMID- 10182313
TI - Story on AHA drew wrong conclusion.
PMID- 10182315
TI - Special report. While you weren't sleeping. Hospital chains.
PMID- 10182316
TI - Special report. Healthcare systems ranked by net patient revenues.
PMID- 10182317
TI - Special report. Psychiatric systems post more growth despite consolidation.
PMID- 10182319
TI - Venturing in. Healthcare services firms attract large chunk of capital.
PMID- 10182318
TI - Special report. Another year of major growth in outpatient care. Post-acute care.
PMID- 10182320
TI - Portable ICU? New system makes cardiac monitoring moveable.
PMID- 10182321
TI - No answer book. Atlas raises questions about practice variations.
PMID- 10182322
TI - Community solutions. HHS honors model programs to extend health coverage.
PMID- 10182323
TI - Taken to task. Grand jury urges dissolution of Calif. hospital district.
PMID- 10182324
TI - Shifting support. AMA wants individuals, not employers, to buy coverage.
PMID- 10182325
TI - Now comes the campaign. Patient protection seen as issue, but do voters care?
PMID- 10182326
TI - Just like old times. Public pressure is forcing managed care to revert to the
system it replaced.
PMID- 10182327
TI - Solving the Medicare equation. Are margins the most effective way to measure a
hospital's fiscal health?
AB - Citing soaring hospital profit margins, lawmakers froze Medicare hospital
reimbursements for this fiscal year, the first such freeze in history. Critics
counter that profit margins don't paint a fair picture of hospitals' financial
condition. They complain that recent rosy forecasts by congressional Medicare
advisory commissions mask the fact that many hospitals lie on the brink of
financial ruin.
PMID- 10182328
TI - Doing the math. Each method of calculating margins has its shortcomings.
PMID- 10182329
TI - A + B = solution? Merging two Medicare parts might help future solvency.
PMID- 10182330
TI - Market profile. Market pressures? Say what? St. Louis providers profit amid
excess capacity.
PMID- 10182331
TI - Purchasing power surge. Employer coalitions may be on the rise, experts say.
PMID- 10182332
TI - Who foots the bill? HMOs confront the rising popularity of designer drugs.
PMID- 10182333
TI - In a pinch. Lawsuit seeks trustee for hospital after bond default.
PMID- 10182334
TI - Primary Health hires firm to steer turnaround effort.
PMID- 10182335
TI - Reform plans advance. House panel agrees on framework for managed-care bill.
PMID- 10182336
TI - Spreading the safety net. Coalition of private hospitals joins a growing crowd.
PMID- 10182337
TI - Parting shots. PPMs sue doc who tried to end management contracts.
PMID- 10182338
TI - 'Dumping' settlements jump. 17 hospitals in 11 states reach agreements with feds.
PMID- 10182339
TI - Backpedaling on rollout. HCFA decides to delay, rework beneficiary handbooks.
PMID- 10182340
TI - New rules for telemedicine. Medicare plans to pay for interactive consultations
only.
PMID- 10182341
TI - Legion airs proposal. Other groups question plan to open VA hospital doors.
PMID- 10182342
TI - Sweaty palms time. AHERF's (Allegheny Health, Education and Research Foundation)
bid to sell hospitals and avoid red ink fizzles.
PMID- 10182343
TI - Unanswered questions. Joint venture parties struggling to apply revenue ruling.
PMID- 10182344
TI - Stopped at the border. R.I., Mass. systems hit speed bump in trying to merge.
PMID- 10182345
TI - Partly overcast. Hospitals see sunny financials now, clouds ahead.
PMID- 10182346
TI - Hypocritical oath. Some docs profit from growing tobacco while warning patients
that smoking kills.
PMID- 10182347
TI - The best of both plans. Providers hope pluses rule after United-Humana merger.
PMID- 10182348
TI - HMOs in harmony. N.H. plans write common set of preventive-care guidelines.
PMID- 10182350
TI - Groups weigh in on Medicare changes.
PMID- 10182349
TI - Speaking terms. Case raises debate about academic freedom of speech.
PMID- 10182351
TI - Ready, set, go. July 1 is starting point for JCAHO's Oryx performance measurement
system.
PMID- 10182352
TI - Plugging drains. Utility managers offer cost control.
PMID- 10182353
TI - Joining the fray. CHA, AHA warm up to GOP managed-care reforms.
PMID- 10182354
TI - GOP releases final reform proposals.
PMID- 10182355
TI - Baptist execs indicted. Hospital CEO, VPs among 7 charged with Medicare fraud.
PMID- 10182356
TI - GE settles with feds. Competition increased for medical equipment service.
PMID- 10182357
TI - Preliminary picture. Year-end '97 data show hospitals' overall margin at 5.1%.
PMID- 10182358
TI - Missing marketing. Study: Medicare HMOs ignore disabled, ailing in ads.
PMID- 10182359
TI - Illinois Blues pleads guilty to fraud.
PMID- 10182360
TI - Short supply. In California, consolidation threatens emergency care.
AB - In the wake of hospital downsizing wrought in large part by managed care,
California is witnessing an alarming shortage of emergency services capacity. In
one prominent case last year, a woman injured in an automobile accident died
after emergency personnel carted her to three hospitals trying to find an ER that
was staffed to care for her properly. Officials warn that it's an issue that has
national significance.
PMID- 10182361
TI - Practices make perfect. Acquisitions of doc groups continue at a steady clip.
PMID- 10182362
TI - Bedsores: $1 billion burden. N.Y. peer review organization tries education to
stop a preventable problem.
PMID- 10182363
TI - Change of heart. N.J. expansion of cardiac CONs proving controversial.
PMID- 10182364
TI - The going gets tough. United-Humana deal draws federal, state scrutiny.
PMID- 10182365
TI - Managed care finds itself in the hot seat. Patients' rights bills, cost increase
loom.
PMID- 10182366
TI - Toward benchmarking medical research--defining and applying key performance
indicators in the measurement of research output.
PMID- 10182367
TI - Safety recommendations for laser pointers.
AB - The use of laser diode pointers that operate in the visible radiation region (400
760 nm) is becoming widespread. These pointers are intended for use by educators
while presenting talks in the classroom or at conventions and meetings. They are
also useful in any situation where one needs to point out special items during
any instructive situation. The pointers can be purchased in novelty stores, mail
order magazines, office supply stores, common electronic stores, and over the
internet. The power omitted by these laser pointers ranges from 1 to 5 mW. The
potential for hazard with laser pointers is generally considered to be limited to
the unprotected eyes of individuals who might be exposed by a direct beam
(intrabeam viewing). No skin hazard usually exists. There are, however, even more
powerful laser pointers now appearing. The units are imported into the U.S. often
without proper manufacturer certification or labeling. The potential for hazards
with these devices is not well understood by the general public and workers, and
numerous exposure incidents have been recorded by the authors. Users of these
products need to be alerted to the potential hazards and be encouraged to follow
appropriate safety recommendations. These factors are discussed and safety
recommendations for laser pointers are presented.
PMID- 10182368
TI - Whistling past the graveyard: don't let your equipment decisions haunt you.
PMID- 10182369
TI - Proposed HCFA regulations offer telemedicine opportunities.
PMID- 10182370
TI - Improving telepresence during consultations.
PMID- 10182371
TI - Telemedicine and special needs children.
PMID- 10182372
TI - Communications special need profiles.
PMID- 10182373
TI - Telemedicine training, military style.
PMID- 10182374
TI - Home-based rehabilitation technology.
PMID- 10182375
TI - Basic medical digital imaging.
PMID- 10182376
TI - Strategies for delivering tele-home care--provider profiles.
AB - Tele-home health care is expanding, and it is easy to say why. There are about
1.5 million home health visits each day in the U.S. For the substantial fraction
of these that are staffed by a Registered Nurse, the average cost/visit is nearly
$90. Several small studies have shown that the cost per visit for a tele-home
visit is about $20-$30--that is, one third, or less, the price of an onsite
visit. This is due, of course, to the substantial overhead in an on-site visit:
the automobile and the time spent driving and parking. The same nurse that can
visit only 5 or 6 patients in their homes each day can see 15-25 patients daily
using telenursing technology. Increasingly, this efficiency is starting to compel
the attention of strategic planners in healthcare. Tele-home nursing uses a
variety of video and telemonitoring technologies. These can be configured to
connect the patient to a nursing call center or to a specific practitioner. In
the past we've reviewed tele-home nursing and call-center services extensively,
most recently in our December 1997 issue. With this story we take a close look at
individual companies and the way they are integrating new technologies into
service-delivery programs.
PMID- 10182377
TI - Failure by design.
PMID- 10182378
TI - Dateline/North America.
PMID- 10182379
TI - Beyond welfare reform: spurring business growth in the inner city.
PMID- 10182380
TI - Looking at burn care.
PMID- 10182381
TI - Creating a dialogue about alternative systems.
PMID- 10182382
TI - The effects of socioeconomic status on exercise and smoking: age-related
differences.
AB - The aim of this article is to examine the effects of socioeconomic status (as
measured by education, income, and labor force status) on patterns of exercise
and smoking for three age groups: persons aged 25 to 44, 45 to 64, and 65 and
over. Two hypotheses drawn from the literature are tested: (a) that
socioeconomic status is associated with risky lifestyle behaviors and (b) that
the effect of socioeconomic status is greater for younger and middle-aged groups
than for older age groups. Logistic regression analyses are performed on the
1990 Canadian Health Promotion Survey. Our results indicate that socioeconomic
status affects health behaviors in relatively important ways, but this depends on
the measure, the specific behavior, and the age group. The findings are
discussed in relation to controversies about the existence of a culture of
poverty and its impact on health behaviors, as well as to several age pattern
hypotheses.
PMID- 10182383
TI - Seniors' attributions for task performance difficulties: implications for
feelings of task efficacy.
AB - Some seniors face difficulties carrying out simple everyday tasks such as opening
containers and turning doorknobs. This study began with the premise that seniors'
appraisals about such difficulties may have consequences for feelings of task
efficacy (e.g., feelings of control and optimism). Attributions to poor product
design (an external/environmental factor) and to limitations (an
internal/personal factor) were considered in addition to joint attributions to
both factors. After controlling for health and gender, type of attribution for
task difficulties was found to relate to feelings of task efficacy. Overall, the
results suggest that seniors may be advantaged by viewing their performance
difficulties as a consequence of poor product design. Compared to their
counterparts, these individuals reported the highest levels of control, ability
to cope, optimism, and beliefs about overcoming problems. Individuals who made
joint attributions reported feeling most helpless and unable to cope with the
present problems.
PMID- 10182384
TI - Use of community-based long-term care services by older adults.
AB - This study uses a previously validated model of disease, disability, functional
limitations, and perceived health to predict the use of long-term care (LTC)
services in and out of the home. The focus is on (a) the direct effects of the
structure of health status on the use of LTC services, (b) how the use of LTC
services differs by race and sex, and (c) how the use of LTC services varies by
in-home and out-of-home location. The findings indicate that different
dimensions of health status affect in-home health services for White men and
women, compared to Black women. Basic ADLs are significant predictors among
Whites but not among Black females. In addition, sociodemographic and
socioeconomic factors are more important influences on the use of out-of-home
services than are health status variables. Some of these effects indicate that
LTC services are being used by the special groups to which they are targeted
(e.g., those living alone). The failure to find other effects (e.g., dependence
on social security for income) indicates that the LTC services are not being used
more by some targeted groups (e.g., the poor). These findings suggest that
simply expanding the supply of LTC services could exacerbate the existing
disparities in service use.
PMID- 10182385
TI - Secular trends in hip fracture occurrence and survival: age and sex differences.
AB - The National Hospital Discharge Survey was used to analyze secular trends from
1965 to 1993 in hip fracture incidence and in-hospital survival in the White U.S.
population 50 years of age and older. Age-specific fracture rates increased
significantly for males in age groups 80-84 years and 85 years and older but not
for younger males. For females, age-specific rates did not change significantly
over the time period. Age-specific survival rates increased for both older males
and females, but the increase was greatest for the older men. Why hip fracture
incidence is increasing in older males but not in females and younger males is
not clear. But the high lifetime prevalence of smoking in the older cohort of
males may be a factor. With rising incidence rates in elderly males, prevention
efforts, which have focused primarily on women because of their high fracture
rates, should target both sexes.
PMID- 10182386
TI - Factors predicting assistive device use in the home by older people following
rehabilitation.
AB - The purpose of this article is to (a) describe the pattern of assistive device
use by older adults the first 3 months home following rehabilitation, (b) examine
factors that predict home use, and (c) describe characteristics of users. The
study involved 86 patients 55 years of age or older who were hospitalized for a
stroke, orthopedic deficit, or lower limb amputation and discharged home with
assistive devices. Of the 642 devices provided in the hospital, 50% were used
frequently to always, with those using devices in Month 1 continuing over time.
A respondent's expectation while hospitalized to use devices was an independent
predictor of actual home use. Although there were no differences between users
and nonusers among sociodemographic variables, respondents with a lower limb
amputation used devices with greater frequency than those with either a stroke or
orthopedic deficit.
PMID- 10182387
TI - Education-specific estimates of life expectancy and age-specific disability in
the U.S. elderly population: 1982 to 1991.
AB - The authors used mortality data for 1982 to 1991 linked to survey records from
the 1982, 1984, and 1989 National Long Term Care Surveys to calculate gender
differences over age in mortality and functional status for high (8 or more years
of schooling) and low (less than 8 years of schooling) education subgroups.
Males and females with high education maintained better functioning at later ages
than those with low education. The authors also found that mortality was higher,
after conditioning on disability, in both the male and female low-education than
the male and female high-education groups. The size of the education effect on
both disability and mortality was large, for example, about 7.6 years difference
in female life expectancy at age 65; a roughly 2-year difference for males.
PMID- 10182388
TI - Risk of behavior problems among nursing home residents in the United States.
AB - This study identified personal risk factors associated with behavior problems
among nursing home residents using data based on a national survey of nursing
home residents. Data are based on the Institutional Population Component of the
1987 National Medical Expenditure Survey and include nursing home residents
living in licensed facilities on January 1, 1987. Multiple regression analyses
were conducted to examine characteristics of residents that place them at risk of
behavior problems. Independent variables include physical functioning, sensory
impairment, cognitive impairment, psychiatric diagnoses, and demographics.
Eleven behavior problems grouped into four categories based on factor analysis
serve as dependent variables: wandering/safety, aggressive behaviors, collecting
behaviors, and delusions/hallucinations. Risk factors emerging as predictors
included sex (male), cognitive impairment, ADL dependency, incontinence,
psychiatric history, receptive communication, walking, and difficulty seeing.
Risk factors differ by type of behavior problem. Results suggest a multiple
etiology in which biological, psychological, and sociocultural factors all play a
role in generating behavior problems in the long-term care setting.
PMID- 10182389
TI - Does geriatric evaluation and management improve the health behavior of older
veterans in psychological distress?
AB - A randomized, controlled trial compared prospective 16-month health service use
among 160 frail, elderly veterans receiving outpatient geriatric evaluation and
management (GEM) or usual primary care (UPC). In this secondary analysis,
multivariable regression was used to determine if the psychosocial assessment and
support provided by the GEM team moderated the use of medical services by
patients in psychological distress. The results indicate that GEM reduced
outpatient use among patients who scored higher on a measure of somatization (p
less than or equal to .05), but GEM increased outpatient use among patients with
higher manifest anxiety (p less than or equal to .05) Psychological distress was
not a factor in the use of inpatient services. GEM had a modest beneficial
effect on the health behavior of frail older persons manifesting some symptoms of
psychological distress.
PMID- 10182390
TI - Mental health services and the mortality of nursing home residents.
AB - This article examines the impact of mental health services on the mortality rate
for mentally ill nursing home residents. Previous research has documented the
unmet need for mental health services among nursing home residents. Some research
using small data sets has indicated patient benefits from treatment. This
article examines the issue using data from the nationally representative National
Nursing Home Survey. In a series of multivariate logistic regressions, treatment
for mental illness provided by either general practice physicians or by mental
health specialists appears to have few impacts on mortality. A statistically
significant treatment effect is found only for residents with schizophrenia,
other psychoses, or anxiety disorders when treated by mental health specialists.
The results are discussed with reference to ongoing reforms for mental health
care in nursing homes.
PMID- 10182391
TI - Need assessment of visiting nursing and rehabilitation services for
noninstitutionalized elderly.
AB - The author assessed the potential need for visiting nursing and rehabilitation
services on a national level to estimate the volume of services expected for
Japan's proposed new long-term care insurance. Baseline data were obtained from
the national survey on freestanding visiting nursing stations conducted in
September 1994, in which the population of 18,500 patients was professionally
assessed by visiting nurses. The baseline data were then applied to the national
sampling survey on households conducted in June 1992, in which respondents self
reported their activities of daily living (ADL) and health status. There are
estimated to be 836,000 noninstitutionalized elderly with disability. Their need
for visiting nursing and rehabilitation services is expressed as 48.26 million
visits or 57.33 million working hours annually. Current service volume accounts
for only 5% of the potential need, suggesting a sharp rise in demand once the new
insurance is fully implemented.
PMID- 10182392
TI - Elderly persons' interpretation of a bodily change as an illness symptom.
AB - Based on a community random sample of 406 elderly, factors that persuade an
elderly person to interpret a bodily change as a symptom of illness are
described. Three measures of such illness interpretation among 27 different
bodily changes are used in analysis: giving an illness label to the change,
consulting a physician for it, and/or using self-care for treatment. The three
types of representations across all 27 bodily changes taken together, as well as
among five typical complaints most commonly experienced, are reported. The
findings show that the perceived seriousness of the bodily change and the general
health context of the older person in which it has occurred are conducive to
interpreting a bodily change as an illness symptom.
PMID- 10182393
TI - Selection bias in samples of older twins? A comparison between octogenarian twins
and singletons in Sweden.
AB - Twin studies are a powerful approach for estimating genetic and environmental
influences in later life, but the usual requirement that both twins are alive may
introduce a selection bias in gerontological studies relative to representative
samples of nontwins. In the present study, samples of older twins and nontwins
in Sweden were compared across the domains of vitality, well-being, physical and
cognitive functioning, and health utilization to evaluate possible selection
bias. One member of each twin dyad in the OCTO-Twin Study of intact twin pairs
older than age 80 was randomly selected (N = 128) and compared with a population
based sample of nontwins (N = 324) from the OCTO Study. Multiple regressions
adjusting for differences in demographic variables showed significant effects for
twin status in only 3 of 20 comparisons. The results suggest that twin pairs
surviving into very late life are similar to a representative sample of nontwins
of the same age in health status and biobehavioral functioning. These findings
support the generalizability of twin studies for understanding genetic and
environmental influences on aging, health, and behavior.
PMID- 10182394
TI - Predictors of disability in the final year of life.
AB - Disability among deceased subjects in the Duke Established Population for
Epidemiologic Studies of the Elderly (EPESE) survey was analyzed to determine the
risk of becoming disabled before or during the final year of life and the
predictors of this disability. The method was a comparison of the baseline
characteristics of decedents who became disabled with the characteristics of
decedents who were not disabled. It was found that 63% of the initially
nondisabled who survived to the next interview remained able to do the basic
activities of daily living without help, at least until a few months before
death. Multivariate analysis showed that initial age, income, depression, and
self-rated health were strong and independent predictors of becoming disabled.
The findings suggest that reducing poverty, depression, and illness may reduce
the risk of disability in the final year.
PMID- 10182395
TI - Benefits of linkage to the National Death Index in the Longitudinal Study of
Aging.
AB - To reduce the potential bias resulting from differential loss to follow-up in the
Longitudinal Study of Aging (LSOA), information obtained from household contact
methods was supplemented with information from the National Death Index (NDI).
This article examines the degree of agreement in the vital status data from two
sources (reinterview contacts and the NDI system) and evaluates the potential
gains of using the NDI data as a supplement to define participants' vital status.
Results reveal that NDI information, used to supplement reinterview information,
can substantially reduce bias due to the differential loss of participants to
follow-up. Reliance on reinterview information alone was less likely to capture
those deaths occurring in study participants who at the initial contact lived
alone, were below the poverty index, were interviewed without use of a proxy, did
not supply a phone number, and did not own a home.
PMID- 10182396
TI - Race, finding meaning, and caregiver distress.
AB - This study investigated the relationship between race, finding meaning (as a
positive psychological resource variable), and the outcomes of caregiver
depression and global role strain among 77 African American and 138 White spouse
caregivers of persons with dementia. Finding provisional meaning had a direct
negative relationship with depression and global role strain. Although African
American caregivers were less likely to report depression and role strain, there
was no interaction by race in the process influencing caregiver distress.
PMID- 10182397
TI - Predictors of mammography use in the past year among elderly women.
AB - Thirty-two personal characteristics were examined as potential predictors of
mammography use in the past year in a geriatric clinic. Interviews assessed
demographic, health status, health service utilization, health belief, and
psychological and social variables (n = 242, mean age = 76 years). Four
variables were independently associated with mammography use in logistic
regression analysis: age, historical mammography use, perceived severity, and
perceived barriers. The inverse relationship between age and mammography use in
the past year was not modified by health status, functional status, and the other
independently predictive variables. The authors conclude that geriatrics
specialty care does not eliminate the age-associated decline in mammography use
that has been previously described. The factors associated with mammography use
in this sample were similar to those that have been described in younger
populations of women. Variables examined because of specific gerontologic
considerations were not independently associated with mammography use in the past
year.
PMID- 10182398
TI - Receptivity to protective garments among the elderly.
AB - Hip fractures among elders resulting from falls are a growing concern as the
proportion of elders increases and health care costs mount. A recent innovation
is the development of an undergarment worn to protect against hip injuries. This
study attempted to determine whether a community population of elders would be
receptive to wearing such a garment and the characteristics of those who would
and would not be receptive. It was assumed that receptivity can be predicted by
variables that have been shown to relate to risks of falling. Predictor
characteristics represent three domains: demographic/predisposition,
health/mobility, and social support. A logistic regression procedure was
employed to determine the probability and odds of receptivity among elders given
a profile of specific characteristics. Results were interpreted with reference
to past research on risks of falling.
PMID- 10182399
TI - Predictors of decreased self-care among spouse caregivers of older adults with
dementing illnesses.
AB - This study describes the health behaviors (alcohol consumption, exercise, sleep
patterns, smoking, and weight maintenance) of a sample of older adult spouse
caregivers (N = 233) and investigates the predictors of decreased self-care since
caregiving began. Multiple regression results indicate that caregivers who
experience greater developmental burden, report a greater number of depressive
symptoms, perform a greater number of activities of daily living (ADL) tasks in
caregiving and spend more hours in a day providing care, and who have lower self
efficacy for both self-care and spouse care are at greater risk for negative
health behavior change. Results have implications for the identification of
caregivers who may be particularly vulnerable to the negative health impact of
caregiving.
PMID- 10182400
TI - Impact of psychosocial factors on health outcomes in the elderly. A prospective
study.
AB - One hundred and thirty-five initially healthy men and women older than 65 years
of age were studied prospectively to identify factors associated with health
outcomes. At study onset, measures of personality, social interaction, and
health locus of control were obtained while participants were still healthy. A
reliable health outcome measure was developed, based on the annual objective
coding of morbidity. Correlations between variables showed significant
associations between age, a less independent personality trait, and poor health
outcomes. Anxiety and low levels of social interaction were associated with poor
health after 8 years. Gender and health locus of control were not significantly
related to health outcomes. A path analysis showed significant direct paths
between age and trait anxiety and 8-year health outcomes, and indirect paths
between anxiety and extroversion and 8-year health, by way of social interaction.
There was no evidence that social interaction mediated the effects of either
anxiety or extroversion on health. The structure of psychosocial characteristics
of the healthy elderly sample was revealed in the pattern of correlations between
personality, social interaction, and locus of control.
PMID- 10182401
TI - Race differences in the health of elders who live alone.
AB - This investigation was initiated to determine whether older African Americans who
live alone are in poorer health than their White counterparts who live under the
same circumstances. Data on 5 measures of health were collected in telephone
interviews with a stratified random sample of community-dwelling elders (n =
1,189). Analysis of weighted data indicate that there were fewer differences in
health by race among older persons who lived alone compared to elders who lived
with others. Where racial differences in health did exist among older adults who
lived alone, the differences could only sometimes be accounted for by population
composition factors that are known to influence health.
PMID- 10182402
TI - Memory complaint as a predictor of cognitive decline: a comparison of African
American and White elders.
AB - Of a representative, racially mixed community sample of older adults in North
Carolina, 59% of Whites and 49% of African Americans reported worsening memory.
The complaint about memory was positively correlated with age, depressive
symptomatology, and physical function but not with level of cognitive function as
measured by the Short Portable Mental Status Questionnaire (SPMSQ) at baseline.
In a controlled analysis of longitudinal data, initial SPMSQ score, age, African
American race, lower education, depressive symptomatology, and physical deficits
at baseline, but not memory complaint, predicted a decline in cognitive function
as measured by the SPMSQ 3 years later. Whereas African Americans were less
likely to complain of deterioration in memory, actual decline as measured by the
SPMSQ was greater for African Americans than for Whites.
PMID- 10182403
TI - Do proxy evaluations of health status predict mortality?
AB - The ability of self-evaluations of health to predict mortality remains despite
efforts to explain their contribution. To further the understanding of global
evaluations, this study investigated whether proxy evaluations of health status
also predict mortality. Data from the Longitudinal Study of Aging were used.
For men and women, the unadjusted odds ratios for proxy evaluations exhibited a
monotone relationship to 3-year and 7-year mortality rates and were predictive of
7-year mortality. This monotone relationship remained even after controlling for
other factors when predicting 7-year mortality rates. However, only the fair and
poor evaluations were significant, and only for men. The adjusted relationship
when predicting 3-year mortality was not completely monotone, although good and
poor proxy evaluations were significant. This suggests that proxy evaluations
are useful, and that there are aspects of health status that are currently
unmeasured but that should lend themselves to being quantified.
PMID- 10182404
TI - Cognitive and emotional predictors of disablement in older adults.
AB - This study focused on the association between aspects of emotional and cognitive
functioning and two stages of the disablement process model, functional
limitations, and instrumental activities of daily living (IADL) disability. The
age- and sex-stratified sample aged 55 to 89 years consisted of 100 inhabitants
of a small Dutch town who scored 24 or higher on the Mini Mental State
Examination (MMSE). Controlling for background factors (health problems, age,
education, and gender), depressive symptoms and fluid intelligence were
independently associated with functional limitations. Of the cognitive functions,
only everyday memory was independently associated with IADL disability.
Emotional functioning was not independently associated with IADL disability.
These findings expand on the disablement process model and demonstrate the
importance of emotional functioning, fluid intelligence, and everyday memory for
the disablement process.
PMID- 10182405
TI - Depression and health in family caregivers: adaptation over time.
AB - This study examined the predictors of caregiver depression and "adaptation" over
time in a sample of 202 family caregivers of cognitively impaired adults. By
examining caregiver adaptation (i.e., a caregiver's ability to adjust
psychologically to the demands of providing long-term in-home care), we were able
to account for initial levels of depression, regression to the mean, and floor
and ceiling effects. Results indicated that the strongest predictors of
caregiver depression 1 year after baseline were initial levels of depression,
worsening of caregiver subjective physical health status and burden, and short
term use of in-home respite assistance. These findings suggest that caregivers
who experience deterioration in levels of physical health and burden and who use
in-home respite on a short-term or sporadic basis may be especially vulnerable to
the chronic stress of providing long-term in-home care.
PMID- 10182406
TI - Predicting discharge outcomes of VA nursing home residents.
AB - This article's purpose was to identify predictors of discharge outcomes of VA
nursing home stays. Using data tapes, diagnostic and assessment data were
assembled on elderly individuals admitted to VA nursing homes nationwide during
Fiscal Year 1987. Six-month outcomes for 3 groups were considered: all residents
(n = 5,895), and those remaining in care after 6 (n = 2,815) and 12 months (n =
1,812), respectively. Logistic regression was used to evaluate predictors of
death and community discharge. Limited activities of daily living (ADL)
dependency, younger age, and receipt of rehabilitation services most consistently
predicted community discharge. ADL dependency, older age, oxygen use, terminally
ill prognosis, malignancy, and congestive heart failure most consistently
predicted mortality. For both dependent variables, predictive ability declined
as stay length increased. Predicting death and community discharge become
increasingly problematic as stay lengthens. Comparing observed versus expected
discharge outcomes has limited usefulness as a quality-improvement tool.
PMID- 10182407
TI - Differential relationships of risk factors to alternative measures of disability.
AB - The purpose of this article was to determine whether risk factors for four
dimensions of disability differ and whether it is legitimate to use aggregated
disability measures in risk factor analyses. Using data from the baseline Duke
Established Populations for Epidemiologic Studies of the Elderly survey (n =
4,162), the authors examined four measures of disability--basic activities of
daily living (ADLs), household ADLs, advanced ADLs, and mobility--and an
aggregated measure consisting of these four measures summed. Sociodemographic
risk factors were examined using stagewise multivariate regression analysis for
the five measures of disability. Weighted least squares with an arbitrary
distribution function estimator were used to determine differences in each risk
factor's performance across the unaggregated measures. Risk factors varied in
strength, presence, and direction of impact across the four dimensions of
disability; as a result, analyses using an aggregated measure were misleading.
PMID- 10182408
TI - Predicting health care utilization in the very old. The role of physical health,
mental health, attitudinal and social factors.
AB - The purpose of this paper is to predict health care utilization in the very old
from a combination of individual-based factors such as physical and mental
health, health attitudes and beliefs, sociodemographic characteristics, and life
circumstances. This study was conducted within the context of the Berlin Aging
Study (BASE). Higher use of medications was most strongly predicted by more
medical diagnoses, better cognitive status, and health attitudes. Physician
contact was only weakly predicted by physical health variables, hypochondriasis,
and living alone. In contrast, living alone was the greatest predictor of the
utilization of increased levels of caregiving services, while having children
nearby served as a protective factor against the need for more formal caregiving
services. These results show that utilization of health care depends on
interaction between physical and mental health, attitudinal, and social factors.
PMID- 10182409
TI - A race- and gender-specific replication of five dimensions of functional
limitation and disability.
AB - Activity of daily living (ADL) and instrumental ADL (IADL) data from the 1989
National Long-Term Care Survey (NLTCS) are used to replicate two domains of
functional status with a total of five dimensions among them. LISREL analysis of
the 14,415 Black and White older adults obtained from the 1989 NLTCS screen
replicates three ADL disability dimensions (basic, household, and advanced) with
few modifications, except among Black males. Similarly, analysis of the 4,297
Black and White disabled older adults replicates five functional status
dimensions (3 ADL disability dimensions plus lower- and upper-body functional
limitation dimensions) with few modifications, except among Black males. These
results suggest that improved understanding of functional status will occur from
studies that take into consideration the differences between functional
limitation and ADL disability. The results also indicate that further research
on the validity of functional reports among Black males is needed.
PMID- 10182410
TI - Weight change: an indicator of caregiver stress.
AB - This study evaluated weight change and caregiver stress in 200 informal
caregivers to elderly patients discharged from a rehabilitation hospital.
Previous laboratory and epidemiologic studies have shown that stress predisposes
to weight change. Nineteen percent of the caregivers had gained or lost at least
10 pounds since becoming caregivers. Weight change was significantly associated
with higher scores on standardized measures of burden and stress (e.g., Burden
Interview, Perceived Stress Scale, Geriatric Depression Scale) and with lower
education, poorer self-rated health, more psychotropic medication use, and caring
for patients with more ADL limitations who had been hospitalized for stroke or a
frail elderly condition. Caregivers to patients with a stroke or frail elderly
condition reported 2.8 times more weight change than caregivers to patients with
a rehabilitation problem. These results suggest that weight change is a valid
indicator of stress in caregivers, and they have public health, clinical, and
research applications.
PMID- 10182411
TI - Stressful life events and depressive symptoms among the elderly. Evidence from a
prospective community study.
AB - We examined the effect of a series of common stressful life events on change in
depressive symptoms among the elderly. The subjects were 1,962
noninstitutionalized people 65 years of age or older from the New Haven EPESE
project. Multivariate regression models revealed that 8 of 11 stressful life
events examined predicted change in depressive symptoms at follow-up (1985) after
controlling for baseline depressive symptoms age, socioeconomic factors,
functional status, and chronic conditions. In addition, the total number of
stressful life events was significantly associated with higher CES-D depression
scores. A dose-response relationship between cumulative life event stress and
change in depressive symptoms was also shown. These results suggest that certain
common life event stressors may have an impact on mental health, both singly and
in combination.
PMID- 10182412
TI - Factors of nutritional health-seeking behaviors. Findings from the Georgia
Centenarian Study.
AB - Health-seeking behaviors are described by Harris and Guten (1979) as any behavior
of an individual that promotes, protects, or maintains one's health, regardless
of actual or perceived health status. The purpose of this study was to determine
if nutritional health-seeking behavior (Bausell, 1986) comprised one or more
factors for older adults (N = 256). Participants were in their 60s (n = 90), 80s
(n = 91), and 100+ (n = 75). Exploratory factor analysis indicated that
nutritional health-seeking behavior items formed two factors: avoid (i.e.,
avoiding unhealthy nutritional behavior) and seek (i.e., attempting or seeking
healthy nutritional behavior). Multiple regression analysis revealed that risk
factors for poor nutritional health-seeking behaviors in older adults include
advanced age, low economic resources, and male gender. Protective factors
included in the personality factors of self-discipline, enthusiasm, sensitivity,
and warmth.
PMID- 10182413
TI - Remaining active in later life. The role of locus of control in seniors' leisure
activity participation, health, and life satisfaction.
AB - Although the physical and psychological benefits of feeling in control are well
documented in the research literature, the mechanisms that account for these
effects have received less attention. The present study was designed to examine
the potential mediating role of exercising and participation in nonphysical
leisure activities, such as attending cultural events, involvement in volunteer
organizations, and so on, in the relation between perceived control and well
being in seniors. The results indicated that an internal locus of control was
positively related to exercising and participation in leisure activities.
Exercising and leisure activity participation, in turn, were predictive of better
perceived health and greater life satisfaction. These findings point to the
potential benefits of increasing seniors' sense of control as a means to promote
exercising and to increase leisure activity participation and, consequently, to
enhance well-being.
PMID- 10182414
TI - Changes in living arrangements of functionally dependent older adults and their
adult children.
AB - This study investigated health and sociodemographic variables associated with co
residency patterns among older patients and their adult children following
discharge from an acute care hospital. Data for the analysis were obtained from
172 adult children caring for functionally impaired parents. Logistic regression
was employed to determine the probability that an older parent establishes co
residency with the adult child following hospitalization instead of remaining in
a separate household. Results indicate that the overall level of caregiver
involvement in activities of daily living (ADL) and instrumental activities of
daily living (IADL) were strong predictors of parent and adult children forming a
joint household. Increased household income of caregivers was inversely related
to co-residency. Decisions about co-residency following hospitalization appear
to hinge both on parental need and the resources of the adult child, suggesting
that the decision to move together is largely one of need and not preference.
PMID- 10182415
TI - Long-range antecedents of functional capability in later life.
AB - A number of demographic, social, psychological, lifestyle, and health
characteristics have been advanced as precursors of functional limitation among
those who survive to old age. This study uses data from a 16-year longitudinal
study to examine long-range antecedents of the respondents' level of physical
functional capability in 1991. The model predicting functional capability from
longitudinal data is more complex and more effective for women than for men.
Older age, lower self-rated health, lower functional capability, and lower
physical activity level in 1975 predict 35% of the variation in functional
capability among women in 1991. Only older age and lower self-rated health are
predictive for men and account for just 11% of the variation. These findings
suggest a need for gender-specific models of antecedents of physical functional
limitations in later life.
PMID- 10182416
TI - The buffering effect of a computer support network on caregiver strain.
AB - ComputerLink was a computer support network for family caregivers of people with
Alzheimer's disease. In a 12-month experiment, 102 caregivers were randomly
assigned to an experimental group that had access to ComputerLink or to a control
group that did not. This investigation examined whether caregivers in the
experimental group had greater reductions in four types of care-related strain by
the end of the 1-year study. ComputerLink reduced certain types of strain if
caregivers also had larger informal support networks, were spouses, or did not
live alone with their care receivers. More frequent use of the communication
function was related to significantly reduced strain for caregivers who were
initially more stressed and for non-spouse caregivers. Greater use of the
information function was related to significantly lower strain among caregivers
who lived alone with care receivers. Overall, ComputerLink appeared to be an
effective tool for reducing strain for some caregivers.
PMID- 10182417
TI - Validity of the Quality of Well-Being Scale for patients with Alzheimer's
disease.
AB - The Quality of Well-Being (QWB) Scale is a utility-weighted measure of health
related quality of life that can be used in clinical trials, population studies,
and cost/utility analyses. This article reports evidence for the validity of the
QWB in patients with Alzheimer's disease. The subjects were 211 patient-spouse
dyads and control dyads recruited from the University of California, San Diego,
Alzheimer's Disease Research Center (ADRC) and from community referrals. Among
these, three quarters were patients, and one quarter were age- and gender-matched
controls. Patient data were obtained by caregiver proxy. Analyses demonstrated
that the QWB was strongly associated with dementia ratings and behavioral
problems. Caretakers of patients with low QWB scores also reported using more
respite time. The authors conclude that the general QWB score allows data from
Alzheimer's disease studies to be used in comparative cost/utility analysis.
PMID- 10182418
TI - Pressure ulcer prevalence in Ohio nursing homes: clinical and facility
correlates.
AB - Pressure ulcers remain a common medical problem in nursing homes, despite the
development of clinical guidelines for prevention and treatment. Prevention
involves low technology but vigilant care. If the disease progresses, infections
can develop, and surgery may be necessary to prevent death. This article
examines pressure ulcer correlates in a representative sample of 15,121 nursing
home residents in 1994 in the state of Ohio. The prevalence of pressure ulcers
was 12%, 8% for Stage 2 or greater. The study found that many nursing home
residents remain at great risk of developing pressure ulcers. Important risk
factors included a history of cured pressure ulcers, new admission and
readmissions, dependencies in activities of daily living, weight loss and
dehydration, diabetes, edema, and incontinence. After controlling for clinical
factors, residents in rural facilities were less likely to have a pressure ulcer.
These findings suggest that the quality of pressure ulcer care in nursing homes
could improve.
PMID- 10182419
TI - The relationship among income, other socioeconomic indicators, and functional
level in older persons.
AB - Socioeconomic status (SES) is well established as a cause of morbidity and
mortality, but relatively few studies have investigated the relationship between
SES and functional level. Functional level is closely related to the use of long
term care services and is a more salient indicator of quality of life than
specific diseases. We used data from 1,570 respondents in the Growing Older in
New York City Study, a probability sample of people age 65 and older, to examine
this relationship. The association between income and function was seen
throughout the full gradient of income and remained significant when controlling
for age, gender, race/ethnicity, household size, education, occupation, age of
immigration, and locus of control. Education and residential environment, but
not occupation, were independently associated with functional level. These
findings support both the association between SES and functional limitation and
the hypothesis that the SES and health association continues into old age.
PMID- 10182420
TI - Older adults and assistive devices: use, multiple-device use, and need.
AB - Responses of older adults ( greater than 65 years) from the 1990 National Health
Interview Survey and Assistive Device Supplement are analyzed to determine if
selected demographic and health variables are associated with the use of
assistive devices, multiple-device use, and the expressed need for such devices.
Bivariate and multi-variate analyses show that, in general, poorer health is
consistently associated with the use of assistive devices, multiple-device use,
and expressed need. Demographic characteristics, however, vary in their
relationships to assistive device use and need. Findings support the importance
of considering multiple-device use and expressed need in studying assistive
devices and older adults.
PMID- 10182421
TI - Beginning counselors' death concerns and empathic responses to client situations
involving death and grief.
AB - Beginning counselors' levels of discomfort and ability to respond empathically to
clients presenting with death-related issues was investigated. Fifty-eight
masters-level counseling students completed the Threat Index and the
Multidimensional Fear of Death Scale and viewed a series of 8 videotape vignettes
depicting clients with death-related (e.g., grief, AIDS) and non-death-related
problems (e.g., marital discord, physical handicap). As hypothesized,
significantly higher levels of counselor discomfort were found in responding to
client situations involving death and dying, especially when these involved
serious illness in the client. In addition, personal fear of death predicted
counselors' distress in death counseling. Contrary to expectations, counselors
were actually slightly more empathic in responding to grief and loss than other
conditions, although the overall level of empathy displayed was low in absolute
terms. The least empathic responses were provided by counselors who construed
death in fatalistic terms on the Threat Index, and who were "saturated" with
death themes by the completion of death attitude questionnaires prior to viewing
the videos. The authors concluded that death and loss counseling presents unique
challenges to beginning mental health providers, especially for those whose
personal death anxieties leave them vulnerable to such work.
PMID- 10182422
TI - Lost children, living memories: the role of photographs in processes of grief and
adjustment among bereaved parent.
AB - Drawing on recent developments in the conceptualization of grief (Klass,
Silverman, and Nickman, 1996; Walter, 1996) that note the importance of talking
about lost loved ones as part of maintaining a "continuing bond" between the
living and the dead, this article considers the role of photographs in parents'
adjustment to life without their child and in their negotiation of a more
"comfortable" relationship with the deceased. The contributions that photographs
and other memorabilia make to parents' opportunities to remember their children's
lives (as opposed to their deaths), to facilitating conversations and
reminiscences about their living relationships, and to parents' ability to
introduce "lost" children to people who didn't know them, are explored using
examples drawn from a series of case studies of bereaved parents. Photographs
and other artifacts arising from their children's living can be perceived as the
illustrations of a developing story in which previous and present relationships
may be represented and interrogated for meaning. It is argued that visual
representations of children's lives, no matter how brief, are a crucial feature
of the process of coming to terms with both the fact of the loss and the reality
of the life that has been lived.
PMID- 10182423
TI - Ethnicity and the grief response: Mexican American versus Anglo American college
students.
AB - Responses of 39 Mexican American college students were compared with those of 61
Anglo students via the Grief Experience Inventory. All participants had
experienced, within the prior 2 years, the death of an individual they regarded
as "close." In comparisons of ethnic groups, significant differences were found
on two scales: Loss of Control and Somatization. The Mexican American sample had
higher scores on both scales. While significant gender-related differences were
found on three scales, no interactions between ethnicity and gender were found.
PMID- 10182424
TI - On asking the right questions: personal death vs. brain death in Japan.
AB - This article addresses methodological concerns encountered during the author's
recent fellowship tenure at the University of Tokyo's School for International
Health. His research addressed matters relating to Japanese views of personal
death within the context of the relationship between self and body. He was also
interested in learning more about the extent to which these same views influence
issues in medical ethics, particularly the ongoing debate over brain death and
heart transplantation, which, until June 1997, was legally prohibited. One
critical component in methodology involved interviews and discussions with
prominent scholars representing various disciplines. The key feature in these
meetings centered around specific core questions. The author describes how these
questions underwent significant modifications, and discusses how these
methodological adjustments in effect reveal notions that are substantive and
relevant to the research design pertaining to Japanese views of death, self, and
embodiment.
PMID- 10182425
TI - Content analysis of previously suicidal college students' experiences.
AB - To ascertain actual helpful and unhelpful remarks received from others, 40
previously suicidal students answered open-ended questions about their
experiences and completed the Suicidal Behaviors Questionnaire (SBQ).
Respondents were still moderately suicidal on the SBQ, even though their most
recent suicidal episode was an average of 3 years earlier. Respondents reported
that family, friends, and personal resources were most helpful in keeping them
alive. Those who told someone about their suicidal ideas or plans reported
helpful remarks ("The situation is not worth dying for") that appeared to be
empathic and thoughtful. Those who told no one about their suicidal ideas or
plans, speculated helpful remarks that also appeared to be empathic and
thoughtful. In contrast, unhelpful remarks (e.g., "You are stupid") appeared to
be simplistic and thoughtless. Implications are that those who are suicidal
should be careful in choosing person(s) in whom they confide, and training
modules that give examples of actual helpful remarks might be useful for
students.
PMID- 10182426
TI - Policy options for delivering and financing care at the end of life.
PMID- 10182427
TI - Indigenous self-determination in an age of genetic patenting: recognizing an
emerging human rights norm.
AB - This Note explores how the law can help indigenous people obtain meaningful
control of their genetic material. Part I will briefly discuss the background of
genetics, life patents, and indigenous groups. Part II sets out the domestic
common law and international human rights law and demonstrates that neither
currently provide adequate protection for indigenous peoples. Part III considers
the human right of self-determination in the context of indigenous research and
patenting, and illustrates that an emerging international norm recognizes an
indigenous people's right to control their genetic material. Part IV argues that
Congress should pass legislation to adequately meet the human rights needs of
indigenous peoples generated by the rapid advancement of biotechnology. This
Note concludes that congressional action to protect indigenous peoples is
consistent with domestic and international law, and is a natural advancement of
human rights and responsible state action.
PMID- 10182429
TI - Physician data banks: the public's right to know versus the physician's right to
privacy.
PMID- 10182428
TI - Coming soon to the "genetic supermarket" near you.
AB - Recent medical studies have indicated that synthesized human growth hormone (hGH)
may cosmetically enhance short, but otherwise perfectly healthy, individuals by
adding inches to their final predicted height. In this note, Curtis Kin examines
the legal and ethical implications of such a discovery, arguing that
nontherapeutic hGH treatment is likely the first of many biotechnology and gene
therapy enhancements that may be available to the public in a "genetic
supermarket" of enhancement products. Mr. Kin finds that the current regulatory
framework for biotechnology and gene therapy inadequately regulates unapproved
uses of hGH and fails to address properly its implications for a genetic "race to
perfection." He proposes changes to the current regulatory framework that will
enforce a strict distinction between therapeutic and enhancement applications of
biotechnology and gene therapy. These changes in the law, Mr. Kin reasons, will
help to solve the social and ethical problems posed by these emerging
developments in technology.
PMID- 10182431
TI - Managed care and quality: California reaches for answers.
PMID- 10182430
TI - Cystic fibrosis: looking for another breakthrough.
PMID- 10182432
TI - Assessing medical malpractice jury verdicts: a case study of an anesthesiology
department.
PMID- 10182433
TI - Broad-spectrum group treatment for parents bereaved by the violent deaths of
their 12- to 28-year-old children: a randomized controlled trial.
AB - This study assessed the efficacy of a 10-week broad-spectrum intervention offered
to bereaved parents about 4 months after the deaths of their 12--28-year-old
children due to accidents, homicide, or suicide. For three outcomes of distress
there was a significant interaction between treatment and baseline values for
each outcome for mothers both immediately posttreatment and 6 months later. The
intervention appeared to be the most beneficial for mothers most distressed at
baseline. Fathers showed no immediate benefits of treatment. Further research is
needed to investigate these unexpected results for fathers and to further
characterize those who benefit from similar programs.
PMID- 10182434
TI - Communicated support following loss: examining the experiences of parental death
and parental divorce in adolescence.
AB - Thirty adults who experienced parental death in adolescence (death survivors), 30
who experienced parental divorce in adolescence (divorce survivors), and 60 who
experienced neither (30 potential support providers for each condition) rated the
relative helpfulness of support-intended communications and the helpfulness of
support network members. Few differences were found between death and divorce
survivor groups and between survivor and potential provider groups.
Nonsignificant results were discussed in terms of those elements of grief and
grief support that transcend different loss situations. Differences were
explained in terms of the unique situational demands differentiating parental
death and parental divorce for adolescents.
PMID- 10182435
TI - Death anxiety in young adults as a function of religious orientation, guilt, and
separation-individuation conflict.
AB - Seventy undergraduate participants between the ages of 19 and 30 were assessed
with measures of death anxiety, religious orientation, separation--individuation
conflict, and two dimensions of guilt (need for reparation and fear of
punishment). A multiple regression with death anxiety as the criterion variable
revealed the following variables, listed in order of their contributions to R2,
to be significant predictors: fear of punishment, extrinsic religious
orientation, need for reparation, and separation--individuation conflict. A model
of death anxiety for young adults that addresses the developmental tasks of this
stage is proposed.
PMID- 10182436
TI - The economics of death? A descriptive study of the impact of funeral and
cremation costs on U.S. households.
AB - The death-care industry in the United States has been virtually ignored by policy
makers. Although the industry is highly fragmented, pricing is becoming
increasingly influenced by multinational corporations. This fact coupled with the
market structure for services, consumers' preferences, and the attributes of
death-care services, has resulted in average funeral cost of over $5,000 per
deceased. This figure is over 25 percent higher than the average annual family
welfare payment in the United States. As estimated in this paper, the
distributional effects of a death occurring within a household varies
significantly by income as well as race and ethnicity. The author concludes that
Americans should engage more openly in the discussion of death, increase their
rate of prearrangements, and seek alternatives to the traditional funeral.
PMID- 10182437
TI - The importance of the physician in the generic versus trade-name prescription
decision.
AB - I examine the importance of physicians in the process by which patients receive
either trade-name or generic drugs. Using a dataset on physicians, their
patients, and the multisource drugs prescribed, I find that almost all physicians
prescribe both types of drugs to their patients, but some physicians are more
likely to prescribe generic drugs while other physicians are more likely to
prescribe trade-name drugs. Very little of the prescription decision can be
explained by observable characteristics of individual patients, but all of the
evidence indicates that physicians are indeed an important agent in determining
whether patients receive either trade-name or generic drugs.
PMID- 10182438
TI - Increasing the federal cigarette tax: a means of reducing consumption?
PMID- 10182439
TI - Commercialism in nonprofit hospitals.
AB - The private nonprofit hospital is the dominant organizational form in the U.S.
hospital industry. Various reasons have been advanced for its high market share.
As hospitals undergo massive changes due in large part to changes in payment
practices, there is widespread concern that nonprofit hospitals may become less
committed to noncommercial activities. This may even be more likely when such
hospitals convert to for-profit status. The empirical evidence indicates that,
on average, hospitals of nonprofit and for-profit ownership are similar in the
provision of uncompensated care, the quality of care, and the adoption of
technology. Conversion of a nonprofit to for-profit status does not adversely
affect the provision of uncompensated care on average. However, for-profits are
more likely to be located in areas where consumers have the ability to pay for
care. As hospital markets become more competitive and the opportunity for cross
subsidizing more unprofitable, collective-good activities will become
increasingly difficult. Support for such activities, if they are to exist, will
have to come from explicit public subsidies.
PMID- 10182440
TI - America weighs in.
AB - The share of U.S. adults who are overweight is on the rise. Researchers know who
is obese, and they've got some good ideas about why we're adding pounds. What
they don't have is a proven treatment for what may be the nation's most
threatening health problem after cigarette smoking.
PMID- 10182441
TI - Mending fences: selling AIDS drugs to the gay community.
AB - As more drug companies enter the fray with products to treat HIV and AIDS,
competition could get fierce. Pharmaceutical marketers also have to overcome the
disenchantment within the gay community regarding the medical establishment.
They will have a better chance of success if they understand the history of AIDS
and its relationship to the gay community.
PMID- 10182442
TI - Getting old and staying fit.
AB - The outdoor recreation industry is probably headed for declines in participants,
as creaky baby boomers switch to less vigorous sports. But the drop may not be as
steep as for previous generations, thanks to boomers' lifelong love of exercise.
PMID- 10182443
TI - Eat, drink, and be healed.
AB - Americans are more inclined than ever to treat minor ailments themselves. That
opens huge new markets to companies that sell food and supplements with healing
properties.
PMID- 10182444
TI - Our aching heads.
AB - Just about everyone takes drugstore pain remedies. The fastest growth in this
market could be for heart-attack prevention, but millions of Americans will also
combat headaches, arthritis, and a host of other ailments, generating modest
growth in the number of users into the next century.
PMID- 10182445
TI - The mother market.
AB - Giving a woman good prenatal and maternity care can capture the health-care
spending of her entire family for life. The next decade will bring several
challenges to those who market maternity products and services, including fewer
new moms, fewer babies in many markets, more minority mothers, and the end of
childbearing for the baby-boom generation. The biggest challenge will be to
provide a wide range of high-quality childbirth options in the cost-conscious
world of managed health care.
PMID- 10182446
TI - Why does cancer cluster?
AB - What do Florida sunbathers, midwestern farmers, rural black men, and Long Island
women have in common? They all have higher-than-average risks for certain
cancers. Researchers know that cancer clusters are usually caused by several
factors. As cancer becomes America's leading cause of death, the public will be
keenly interested in sorting out the causes and reducing the risks.
PMID- 10182447
TI - Dentists are forever.
AB - Fluoridated water was supposed to make general dentistry obsolete, yet the
profession is going strong. Preventive dentistry means that fewer mouths need
dentures, but more require repair and restoration of natural teeth and gums.
Demand for dental services will continue to increase.
PMID- 10182448
TI - The air we breathe.
AB - Public attitudes toward smoking are complex, but the facts for businesses are
clear. Second-hand smoke is a major health hazard, and the most unhealthy places
for second-hand smoke are bars and restaurants. While there is little support
for a total smoking ban, selected bans are more popular. Even if new federal
rules don't force restaurants to ban smoking, businesses can gain a competitive
edge by going smoke-free.
PMID- 10182449
TI - Vision in an aging America.
AB - Like it or not, baby boomers' eyes are getting weaker. Older eyes have trouble
with small print, glare, and low-contrast color schemes. They are also more
prone to a variety of eye diseases. Businesses that ignore the fuzzier world of
older eyes may become invisible to a growing share of consumers.
PMID- 10182450
TI - Selling good behavior.
AB - Social marketers use the tools of selling to promote good nutrition, regular
checkups, and other positive behavior. Instead of preaching, they try to
understand and change the complex motivations that lie behind risky activities
like smoking and unsafe sex. AIDS prevention is the vanguard of social marketing
in the U.S., but the practice is likely to spread for a simple reason: it works.
PMID- 10182451
TI - There goes the sun.
AB - Americans are getting more conscientious about blocking harmful rays. But they
could go even further to protect their skin.
PMID- 10182452
TI - People behaving badly.
AB - With every cigarette we smoke, every fat-filled snack we consume, and every lap
we don't take around the track, we risk our health. This state-by-state look at
what we do and don't do reveals poor health practices wherever you look.
PMID- 10182453
TI - The fun factor: marketing recreation to the disabled.
AB - Consumers with physical disabilities are a growing market for travel, sports, and
other leisure-oriented products and services. Many in the forefront of serving
this market have been inspired by personal circumstances and assisted by
technology. Two keys to their success are: careful attention to design and a
positive attitude.
PMID- 10182454
TI - Selling drugs.
AB - Doctors might not be crazy about the idea, but patients are walking into their
offices asking for specific drugs. They have heard about them on TV or read
about them in magazines.
PMID- 10182456
TI - Push down while turning: a new rule will make drug packaging both child-resistant
and "adult-friendly.".
PMID- 10182455
TI - The facts of death.
AB - This tour of the average American's death says a lot about modern life. When and
where we die is largely up to medicine. But trends in how we die and honor our
dead depend more on social change, aging, and demographic diversity.
PMID- 10182457
TI - Beyond the body: an emerging medical paradigm.
AB - As with so many other aspects of American society, the baby boom may be the
catalytic factor that ultimately changes the way we treat our health.
PMID- 10182458
TI - Fertility clinics: what are the odds?
PMID- 10182459
TI - Gum disease: do you need surgery?
PMID- 10182460
TI - The cholesterol question: what you need to know now.
PMID- 10182461
TI - Iron in the diet: do you need supplements?
PMID- 10182462
TI - The virus we could defeat: a new vaccine is underused.
PMID- 10182463
TI - What's the best pain reliever? Depends on your pain.
PMID- 10182464
TI - Drug advertising: is this good medicine?
PMID- 10182465
TI - Dental implants: should you bite?
PMID- 10182466
TI - Will a pill take your pounds off?
PMID- 10182467
TI - Hair loss: does anything really help?
PMID- 10182468
TI - Chronic fatigue syndrome: any closer to an answer?
PMID- 10182469
TI - Keeping your teeth in shape.
PMID- 10182470
TI - Working out the facts: the truth behind ten common myths.
PMID- 10182472
TI - Food poisoning: how to protect yourself from pathogens.
PMID- 10182471
TI - Coffee clutch: should you worry about all that caffeine?
PMID- 10182473
TI - How will you pay for your old age?
PMID- 10182474
TI - Heard it through the grapevine: is wine really good for you?
PMID- 10182475
TI - Prostate cancer: is an imperfect test worth the trouble?
PMID- 10182476
TI - Clearing the air: is our air clean enough?
PMID- 10182477
TI - Asthma and the air you breathe.
PMID- 10182479
TI - Can it happen here? The puzzle of mad cow disease.
PMID- 10182478
TI - Heart disease: how women can reduce their risk.
PMID- 10182480
TI - Marijuana as medicine: how strong is the science?
PMID- 10182481
TI - The mammogram debate: what should women do?
PMID- 10182482
TI - A supplement worth watching: vitamin E hasn't lost its glow.
PMID- 10182483
TI - Is HIV "extraordinary"?
PMID- 10182484
TI - Regulating death: Oregon's Death with Dignity Act and the legalization of
physician-assisted suicide.
PMID- 10182485
TI - Strokes and the South.
PMID- 10182486
TI - Recent developments in employee benefits.
AB - The latter part of 1996 and the first part of 1997 produced continuing changes to
the laws concerning employee benefits, as both Congress and the courts continued
to focus on this area of the law. This article highlights some of the more
important developments during the period with particular focus upon those of
concern to the insurance industry.
PMID- 10182487
TI - Recent developments in health insurance and life insurance case law.
PMID- 10182488
TI - Recent developments in medicine and law.
AB - This article addresses important developments in the field of medicine and the
law during the last year and highlights some of the significant areas of law
affecting health care providers that should be considered. Actions against health
care providers may include challenges to peer review immunity, allegations
concerning the practice of medicine across state lines without a license, and
even accusations of wrongfully assisting a patient to commit suicide. These
areas are addressed in turn by this article. Finally, antitrust developments
over the last year are briefly addressed as an emerging area of concern for
providers forming complex practice networks in today's health care arena.
PMID- 10182489
TI - Recent developments in the public regulation of insurance law.
PMID- 10182490
TI - Recent developments in workers' compensation law.
PMID- 10182492
TI - Crashes, fires, and falls.
PMID- 10182491
TI - Predicting health-care employment.
PMID- 10182493
TI - Use, abuse, and dependency: understanding the addiction process.
PMID- 10182494
TI - Snap happy. Streamlined schedules and payroll keep the beat at Saint Vincent.
PMID- 10182495
TI - Driving the value of IT.
PMID- 10182496
TI - View master. Selecting software requires a strategy that looks beyond features
and functions.
PMID- 10182497
TI - When opportunity knocks. U.S.-based managed care companies help find solutions
for foreign needs.
PMID- 10182498
TI - Payoff in the pacific.
AB - Asia Pacific economies are struggling to cope with the past year's series of
financial catastrophies and regain the market stature and confidence they once
enjoyed. Despite the turmoil, all industries including healthcare continue to
demonstrate their commitment toward privatization and modernization through
technology. Advances in healthcare IT in the Asia Pacific region are narrowing
the differences in healthcare between East and West. Is the information age
speeding healthcare toward a global standard?
PMID- 10182499
TI - Golden labs. Laboratories look to newer systems to streamline labor-intensive
tasks, reduce payrolls and speed turnaround times.
PMID- 10182500
TI - Image is everything.
PMID- 10182501
TI - High finance. Duke chooses to buy vs. build in managing its financial data.
PMID- 10182503
TI - Consumerism in healthcare: it's about time!
PMID- 10182502
TI - Practice brief. Preparing your organization for a new coding system. American
Health Information Management Association.
PMID- 10182504
TI - Patient empowerment--a trend that matters.
AB - Increased patient empowerment will generate an extensive shift in fundamental
roles and procedures in healthcare, including the roles of HIM professionals.
Here's a look at factors influencing patient empowerment and a forecast of how
patient and provider communications are likely to be affected in the future.
PMID- 10182505
TI - Consumer health informatics: the medical librarian's role.
AB - Growing consumer interest in health-related information has created a need for
professionals to manage, provide, and interpret such material. In preparing for
the new demands of the market, HIM professionals can learn from the example of
medical librarians, who are already working to meet those needs.
PMID- 10182506
TI - Advances in health information technology for patients.
AB - Patients now have access to a wide variety of health-related educational material
via computers and other sources. To ensure quality, security, and data integrity,
it is likely that these databases of patient health information will become part
of the information that HIM professionals manage and coordinate for patient use
in the clinical setting. This article describes the health information resources
available to patients.
PMID- 10182508
TI - New possibilities for patient information storage in a technological age.
AB - Are smart cards a viable solution for storing patient information? What about
companies that store and provide emergency medical information? The author
examines the possibilities these services offer.
PMID- 10182507
TI - Long-term care meets information challenges.
PMID- 10182509
TI - Best practices in patient advocacy.
AB - When an insurance claim or treatment authorization is denied, where can patients
turn? More frequently they are turning to patient advocates who understand the
information contained in their claims and medical records. Here's a look at some
opportunities for HIM professionals in this growing field.
PMID- 10182510
TI - Outlining changes in the Joint Commission's sentinel event policy.
PMID- 10182511
TI - What is Gulf War syndrome? (Part II).
PMID- 10182512
TI - One ringy dingy: call centers of the nineties.
PMID- 10182513
TI - Providence Health Plan call center: a case study in innovation and integration.
PMID- 10182514
TI - Customer service call center infrastructure redesign.
PMID- 10182515
TI - Why a call center? And why now?
PMID- 10182516
TI - Integrating heterogeneous healthcare call centers.
AB - In a relatively short period, OHS has absorbed multiple call centers supporting
different LOBs from various acquisitions, functioning with diverse standards,
processes, and technologies. However, customer and employee satisfaction is
predicated on OHS's ability to thoroughly integrate these heterogeneous call
centers. The integration was initiated and has successfully progressed through a
balanced program of focused leadership and a defined strategy which includes site
consolidation, sound performance management philosophies, and enabling
technology. Benefits have already been achieved with even more substantive ones
to occur as the integration continues to evolve.
PMID- 10182517
TI - Managing care through high-quality, customer-focused service: HealthCall.
PMID- 10182518
TI - A call center primer.
AB - Call centers are strategically and tactically important to many industries,
including the healthcare industry. Call centers play a key role in acquiring and
retaining customers. The ability to deliver high-quality and timely customer
service without much expense is the basis for the proliferation and expansion of
call centers. Call centers are unique blends of people and technology, where
performance indicates combining appropriate technology tools with sound
management practices built on key operational data. While the technology is
fascinating, the people working in call centers and the skill of the management
team ultimately make a difference to their companies.
PMID- 10182519
TI - Call centers in healthcare: the experience of one health maintenance
organization.
PMID- 10182520
TI - How technology can make you a hero with your customers.
PMID- 10182522
TI - Developing Web-based knowledge management systems for healthcare call centers.
PMID- 10182521
TI - Creating a vision for your medical call center.
AB - MCC technologies and applications that can have a positive impact on managed care
delivery are almost limitless. As you determine your vision, be sure to have in
mind the following questions: (1) Do you simply want an efficient front end for
receiving calls? (2) Do you want to offer triage services? (3) Is your
organization ready for a fully functional "electronic physician's office?"
Understand your organization's strategy. Where are you going, not only today but
five years from now? That information is essential to determine your vision. Once
established, your vision will help determine what you need and whether you should
build or outsource. Vendors will assist in cost/benefit analysis of their
equipment, but do not lose sight of internal factors such as "prior inclination"
costs in the case of a nurse triage program. The technology is available to take
your vision to its outer reaches. With the projected increase in utilization of
call center services, don't let your organization be left behind!
PMID- 10182523
TI - Developing a successful call center: one hospital's story.
AB - As our call centers continue to respond to changes in the healthcare industry and
to customer demand, we understand that it is constantly necessary to reinvent8
ourselves. The call center industry, is, after all, only about 20 years old. It
is constantly responding to technological advances. Medical call center managers
must also respond to changes in healthcare delivery. We must keep a vigilant eye
on industry trends. While we welcome information on other call centers to help us
reformulate our targets, we must always customize information to our local
market.
PMID- 10182524
TI - Dr. Clinton scrubs up.
PMID- 10182525
TI - Too high in California?
PMID- 10182526
TI - Will you manage your organization's culture or, will it manage you?
PMID- 10182527
TI - Who's your best customer?
AB - Conventional wisdom holds that the best customers and prospects for managed care
are the healthiest consumers. This is true only because of the meager extent to
which premiums can be adjusted for varying risk among individuals. If a decent
health/risk adjustment system were used, the best consumers for managed care to
go after would be the highest-risk, highest users of health care, provided only
that risk and use can be improved. The healthiest consumers have both the least
potential for improvement and the least reasons for loyalty.
PMID- 10182528
TI - Major purchasers view customer service.
AB - While managed care organizations may select a variety of strategies toward
customer service, the most successful will be adapting their approach to the
expectation and requirements of major purchasers. In order to better understand
the perspective of the individuals who are responsible for policy decisions at
that level, Managed Care Quarterly (MCQ) conducted interviews with three highly
respected representatives.
PMID- 10182529
TI - Bringing international patients to American hospitals: the Johns Hopkins
perspective.
AB - American health care institutions are reaching out to the foreign market,
assiduously cultivating patients from overseas. This innovative strategy,
designed in part to help U.S. medical centers cope with cuts in federal funding,
HMO pressures, and decreasing patient volumes, dovetails nicely with the current
climate of global expansion in business and worldwide awareness of American
medical expertise. This article describes the International Services Program at
Johns Hopkins Hospital. The author and program director addresses its origins,
implementation, outcomes, and the obstacles planners faced in launching a
vigorous, international outreach initiative.
PMID- 10182530
TI - Becoming customer-driven: one health system's story.
AB - Market research was done by Crozer-Keystone Health System to better understand
the new health care consumer. The information will assist in developing,
promoting, and delivering products and services of maximum value to current and
prospective consumers. The system is responding by bundling and delivering
products and services around consumer-based dimensions, developing new and better
ways to improve customer convenience, access, and service. Operationalizing these
initiatives for change involves building an information infrastructure of
extensive content and customer databases, using new technologies to customize
communications and ultimately service components.
PMID- 10182531
TI - Beyond utilization control: managing care with customers.
AB - Allina Health System embarked on a rigorous process to better understand the
customer's perception of care and service. The milestone for quality is the
participation of the patient, member, and family in the health care system to
determine care and service quality. The challenge for those in health care is to
understand and manage the complex cultural changes this inclusion implies.
PMID- 10182532
TI - Patient choice organizations: the next generation after capitation and managed
care.
PMID- 10182533
TI - Provider sponsored organizations: emerging opportunities for growth.
AB - As providers struggle to identify mechanisms to serve the Medicare population,
the Medicare program continues to evolve. Of course, providers may serve the
beneficiaries through traditional Medicare, Medicare HMOs, or a Medicare Select
product, but as this book shows, under the appropriate conditions, the best way
may be through the formation of a PSO.
PMID- 10182534
TI - Regulating managed care plans: is the telecommunications industry a possible
model?
AB - Merger mania has been a striking trend in the health and managed care fields
during the last decade, promising to improve integration of services, decrease
excess capacity, enhance price competition, and increase the ability of providers
and insurers to handle risk-based payment. In view of these promises, our first
argument in this paper is that undoubtedly strong, well-financed managed care
plans and health networks will continue to utilize the merger concept to acquire
additional insurers and providers, eventually gaining more control over the
organization and the financing of a region's health care delivery system. Our
second thesis is that the quasicompetitive, quasiregulatory authority inherent in
the Telecommunications Act of 1996, somewhat similar in concept to the American
Hospital Association's earlier Ameriplan (1970), might serve as an appropriate
model for Congress to use in designing future managed care, health field, and
federal/state governmental interrelationships.
PMID- 10182535
TI - Do TQM interventions change management culture? Findings and implications.
AB - This study assesses the impact of TQM/CQI interventions on the culture and
performance of top management teams. The findings suggest culture is related to
performance but that TQM/CQI interventions are not associated with either
performance or culture change. Implications for additional research and for
practice are discussed.
PMID- 10182536
TI - Contrasting the original Malcolm Baldrige National Quality Award and the Health
Care Pilot Award.
AB - In recent years, interest in establishing a separate health care category for the
Malcolm Baldrige National Quality Award has grown. A 1995 pilot study evaluated a
new set of award criteria specifically designed for the health care industry. The
article discusses the similarities and differences between the two awards,
including the factors that make quality management in the health care industry
more complex.
PMID- 10182537
TI - The evaluation of hospital restructuring efforts: satisfaction, quality, and
costs.
AB - This article reports on study evaluating the effects of hospital restructuring on
patient satisfaction, nurse satisfaction, cost of care, and clinical quality. The
restructuring involved facility redesign, telecommunications enhancement, and
implementation of patient care processes incorporating multiskilled personnel and
case facilitation systems. The results indicate improved patient and nurse
satisfaction, decreased length of stay and variable cost per patient day, and
good clinical outcomes.
PMID- 10182538
TI - Implementation of an active management of labor guideline in a managed care
setting.
AB - This article reports on a study assessing the impact of a clinical guideline for
the active management of labor. Modest changes were noted in the process of care
with minimal impact on outcomes. Results might have been enhanced if more systems
had been in place and if provider training had involved more comprehensive
discussion and feedback on each of the components.
PMID- 10182539
TI - Benchmarking the communication of continuous improvement activities.
AB - Communication of a continuous improvement program in a large medical center was
assessed using a formal benchmarking process with four non-health care
organizations. Results indicated that continuous improvement must be integrated
with the corporate strategic plan, must focus on customer satisfaction, and have
active leadership support. A common framework should link different continuous
improvement methodologies. Ongoing, open, multimedia two-way communication is
required. Continuous improvement activities need to be integrated into all
employees' daily work.
PMID- 10182540
TI - A method to track surgical site infections.
AB - We present an approach to assessing the impact of surveillance for surgical site
infections and providing feedback to surgeons on their progress, as part of
continuous quality improvement. Adjusting for patient risk factors using the
Standardized Mortality Ratio, there was a marked decrease over time in both SMR
(1.3 to 0.27) and crude infection rates (32 to 10 per thousand operations per
year). These declines cannot be explained by decreased length of hospital stay.
PMID- 10182541
TI - Engaging clinicians in a quality improvement strategy for early-stage breast
cancer treatment.
AB - Physicians are skeptical of quality improvement and obtaining their enthusiastic
participation continues to be a challenge. We designed and initiated a clinician
driven quality improvement project to improve the provision of efficacious breast
cancer treatments among women presenting to an academic medical center for their
initial treatment of early-stage breast cancer. All 156 identified physicians
agreed to participate in the project and provided access to their office records
or specific medical information.
PMID- 10182542
TI - Life as a dying man.
PMID- 10182543
TI - Good medicine on the Web. The Internet is a powerful health resource, but watch
where you surf.
PMID- 10182544
TI - Get it in writing. Your medical record is like a credit rating. Don't neglect it.
PMID- 10182545
TI - A lab's best friend.
AB - As laboratories become increasingly market-driven lab managers and IT
professionals are looking for ways IT can help them do more with less--and do it
more efficiently and faster--to help ensure their survival.
PMID- 10182546
TI - Shopping for the right consultant.
PMID- 10182547
TI - IT for capitation: getting the whole picture.
PMID- 10182548
TI - Racing toward client-server solutions.
AB - If mainframe computing is like driving a reliable sedan, some experts say client
server computing is like driving a fast, maneuverable sports car. But until you
understand and fine-tune a client-server system, performance can be
disappointing.
PMID- 10182549
TI - What works. Pediatric group cuts staff, billing cycle; reduces claims cost to a
dime with Internet processing.
PMID- 10182550
TI - What works. Children's center maintains R.N. ratio using wireless.
PMID- 10182551
TI - What works. IVR system helps diabetes center triple patient load; increases care
level.
PMID- 10182552
TI - Supplying provider data via the Internet.
PMID- 10182553
TI - HotList: pharmacy systems.
PMID- 10182554
TI - The IT staffing crisis.
PMID- 10182555
TI - Evolution and factors associated with biological-risk accidents reported in a
university hospital in Spain, 1989 to 1995.
AB - BACKGROUND: The objective of this study was to describe the profile and evolution
of accidents involving risk of transmission of hepatitis B virus (HBV), hepatitis
C virus (HCV), and human immunodeficiency virus (HIV) reported in a large Spanish
hospital, together with the preventive measures administered and the factors
associated with high-risk accidents. METHODS: Data used were the accidents
recorded in the hospital during the period from January 1989 to December 1995. A
logistic model, using age, gender, service, occupation, and year of accident as
independent variables was constructed to study the factors associated with these
accidents. RESULTS: The study included 1,009 accidents. Accidents were more
common among nurses, female doctors, younger workers, and persons who worked in
surgical settings. Of the total sources of infection studied, 11.6% were positive
for HBV, 28.2% for HCV, and 24.4% for HIV. No seroconversions were detected in
the partial follow-ups conducted. The factors associated with high-risk accidents
were gender (relative risk [RR], 2.01; 95% confidence interval [CI95], 1.24
3.60); occupation as physician (RR, 2.57; CI95, 1.54-4.29) or as nursing staff
(RR, 1.80; CI95, 1.12-2.89); and working in a surgical service (RR, 2.01; CI95,
1.27-3.18). Younger workers had more accidents overall, but older workers were
more likely to have high-risk exposure. In the multivariate analysis, the
occupation (physician and nursing staff) was the most important variable when
adjusted by the other factors. CONCLUSIONS: Our results suggest that a greater
effort still is required in the application and evaluation of preventive
measures. New safety systems, with clearly proven cost-effectiveness, should be
developed and applied.
PMID- 10182556
TI - Inappropriate antibiotic therapy in febrile cancer patients with bacteremia.
AB - OBJECTIVE: The aim of the study was to assess the outcome of inappropriately
treated cancer patients with documented bacteremia. DESIGN/SETTING: 95 cases of
inappropriately treated bacteremias in febrile cancer patients in a tertiary-care
center were analyzed and compared with a group of appropriately treated
bacteremias to assess risk factors for inappropriate therapy and outcome.
RESULTS: Among 285 bacteremias, 95 (33.3%) were not treated appropriately, with
42 receiving the wrong antibiotics and 17 having too short a therapeutic course
of appropriate antibiotics. In 13, therapy was delayed for more than 48 hours
after the onset of fever. Twenty-three patients did not receive antibiotic
therapy at all despite bacteremia. A group of 95 inappropriately treated
bacteremias was compared to 190 appropriately treated bacteremias occurring in
the same period. Microbiological cure after the initial course of therapy was
achieved more often (76.8% vs 38.9%, P < .001) in the group of appropriately
treated bacteremias in all cases and also in the subgroup of leukemic patients (P
< .01). Overall and attributable mortality were significantly lower in patients
who were treated appropriately. There was no difference in the number of
antibiotics administered in appropriately versus inappropriately treated
bacteremias. Cost of therapy between both groups was similar. CONCLUSIONS:
Inappropriately treated bacteremic cancer patients had outcomes that were
significantly worse than patients who were treated appropriately. The reasons for
inappropriate therapy were selection of the wrong antimicrobials, too short a
duration of therapy, delayed onset of therapy, or absence of antimicrobial
therapy.
PMID- 10182557
TI - Achieving JCAHO accreditation in a university student health center.
AB - Of the approximately 1,500 colleges and universities in the United States, only
approximately 100 university student health centers are accredited by either of
the two major ambulatory healthcare accreditation agencies. The accreditation
process can be daunting. We found few examples in the accreditation literature
that assisted us in our endeavor. This article is designed as a primer to assist
college health center administrators in achieving accreditation by the Joint
Commission on Accreditation of Healthcare Organizations.
PMID- 10182558
TI - Primary-care--physician supply: policy analysis on the state level.
AB - OBJECTIVE: To describe a method for policy analysis on the state level for
understanding frequently overlooked determinants of the current status and
dynamics of primary-care-physician supply. DESIGN: The method used is systems
analysis. The approach takes account of the changing interstate migration,
tracking the professional origins of physicians, their uneven age distribution,
and the considerable time delays in the system. The forecasting mathematical
model consists of the physician-aging submodel, the undergraduate and graduate
medical education submodel, and the migration subsystem. SETTING: The necessary
data were restored fully from the Virginia Board of Medicine archive database.
RESULTS: The analysis shows the outstanding importance of out-of-state migration
for the state of Virginia: approximately two thirds of primary-care physicians
are out-of-state medical graduates. In the next decade, the attrition of primary
care physicians will start to increase steadily because of the prominent bulge in
the physician age distribution. Similar bulges were observed in the age
distributions for some other states. CONCLUSIONS: The method reveals the
underlying mechanisms and principles of physician work-force reproduction. It may
show which goals are feasible, and it may be used in any state for the research
necessary for rational policy formulation.
PMID- 10182559
TI - E-mail medicine: dawn of a new era in physician-patient communication.
AB - Computer-based electronic mail has opened up new opportunities for physician
patient communication. In many ways, electronic communication is more convenient
than either the telephone or the postal service. However, it is important to
recognize the limitations of electronic mail. In this article, we review
important issues and recommend minimal standards for physician-patient
communication via electronic mail.
PMID- 10182560
TI - Behind the physician licensure numbers: false impressions, retirement crisis, and
migration.
AB - This communication examines the supply of primary-care physicians at the state
level. It shows that the number of actively practicing physicians is considerably
less than the number of licensed physicians; the age distribution of primary-care
physicians has a bulge in the ages younger than 50, and this bulge may lead in
the near future to an unexpected increase in physician attrition due to
retirement; and, at the state level, migration may be playing the dominant role
in determining the total supply of primary-care physicians.
PMID- 10182561
TI - Overutilization of indwelling urinary catheters and the development of nosocomial
urinary tract infections.
AB - OBJECTIVE: To assess the impact of the overutilization of indwelling urinary
catheters in the emergency department on the development of nosocomial urinary
tract infection. DESIGN: Prospective cohort study. SETTING: 638-bed tertiary-care
hospital. PATIENTS: 118 consecutive medical and surgical admissions from the
emergency department collected over 3 weeks. INTERVENTION: Catheterized patients
were assessed. The completeness of documentation relating to catheter insertion
and two outcomes were measured: asymptomatic bacteriuria and urinary tract
infection. RESULTS: 24 (20.3%) had catheters inserted, of whom 12 (50%) were
catheterized for justifiable indications. Positive urine cultures were found in
10 of the catheterized patients (42%), 5 of whom fulfilled the definition for
catheter-associated urinary tract infection. Three of the five infections
occurred in patients for whom catheterization was not justifiable. An order was
written for catheter insertion in 62.5% of charts, while the rationale for
catheterization was documented in 16.7%. CONCLUSIONS: Many nosocomial urinary
tract infections are due to the inappropriate placement of indwelling urinary
catheters in the emergency department. The prevention of these infections should
begin with restricting catheterization to those patients for whom it is
appropriate.
PMID- 10182562
TI - Prohibition of "gag clauses" in the Federal Employees Health Benefits Program-
OPM. Final rule making.
AB - The office of Personnel Management (OPM) is issuing a final regulation amending
the Federal Employees Health Benefits Acquisition Regulations (FEHBAR) to
prohibit health benefit carriers participating in the Federal Employees Health
Benefits (FEHB) Program from entering into contracts or employment agreements
with health care providers, provider groups, or health care workers that would
include provisions or financial incentives that have the effect of limiting or
restricting communication of medically necessary services to FEHB enrollees.
PMID- 10182563
TI - Medical devices; 30-day notices and 135-day PMA supplement review--FDA. Direct
final rule; withdrawal.
AB - The Food and Drug Administration (FDA) published, in the Federal Register of
April 27, 1998 (63 FR 20530), a direct final rule to implement the amendments to
the premarket approval provisions of the Federal Food, Drug, and Cosmetic Act, as
amended by the Food and Drug Administration Modernization Act of 1997 (FDAMA).
The comment period closed on July 13, 1998. FDA is withdrawing the direct final
rule because the agency received significant adverse comment.
PMID- 10182564
TI - Universal service order; protective order for non-rural local exchange carriers-
FCC. Policy statement.
AB - This protective order for non-rural local exchange carriers (LECs) is intended to
facilitate and expedite review of documents containing trade secrets and
commercial or financial information submitted by a person or entity that are
either privileged or confidential. It reflects the manner in which "Confidential
Information," as that term is defined herein, is to be treated in the universal
service proceeding to select a mechanism to determine high cost support. The
Order is not intended to constitute a resolution of the merits concerning whether
any Confidential Information would be released publicly by the Commission upon a
proper request.
PMID- 10182565
TI - Biological products regulated under Section 351 of the Public Health Service Act;
implementation of biologics license; elimination of establishment license and
product license; public workshop--FDA. Proposed rule; notice of workshop.
AB - The Food and Drug Administration (FDA) is announcing a public workshop to present
issues related to the agency's proposed rule entitled "Biological Products
Regulated Under Section 351 of the Public Health Service Act; Implementation of
Biologics License; Elimination of Establishment License and Product License"
issued recently in the Federal Register. The purpose of the public workshop is to
provide interested persons an opportunity to more clearly understand the proposed
rule and its effect on industry and the public.
PMID- 10182566
TI - Medicare program; revision of the procedures for requesting exceptions to cost
limits for skilled nursing facilities and elimination of reclassifications--HCFA.
Proposed rule.
AB - This proposed rule would revise the procedures for granting exceptions to the
cost limits for skilled nursing facilities (SNFs) and retain the current
procedures for exceptions to the cost limits for home health agencies (HHAs). It
also would remove the provision allowing reclassifications for all providers.
PMID- 10182567
TI - Medicare and Medicaid programs; quarterly listing of program issuances--fourth
quarter 1997--HCFA. Notice.
AB - This notice lists HCFA manual instructions, substantive and interpretive
regulations, and other Federal Register notices that were published during
October, November, and December of 1997 that relate to the Medicare and Medicaid
programs. It also identifies certain devices with investigational device
exemption numbers approved by the Food and Drug Administration that may be
potentially covered under Medicare. Section 1871(c) of the Social Security Act
requires that we publish a list of Medicare issuances in the Federal Register at
least every 3 months. Although we are not mandated to do so by statute, for the
sake of completeness of the listing, we are including all Medicaid issuances and
Medicare and Medicaid substantive and interpretive regulations (proposed and
final) published during this timeframe.
PMID- 10182568
TI - Medicare program; schedules of per-visit and per-beneficiary limitations on home
health agency costs for cost reporting periods beginning on or after October 1,
1998--HCFA. Notice with comment period.
AB - This notice with comment period sets forth revised schedules of limitations on
home health agency costs that may be paid under the Medicare program for cost
reporting periods beginning on or after October 1, 1998. These limitations
replace the limitations that were set forth in our January 2, 1998 notice with
comment period (63 FR 89) and our March 31, 1998 final rule with comment period
(63 FR 15718).
PMID- 10182569
TI - Federal-State Joint Board on Universal Service--FCC. Final rule.
AB - This Order changes the funding year for the schools and libraries universal
service support mechanism from a calendar year cycle to a fiscal year cycle. This
Order also adjusts the amount of money available for schools and libraries, and
rural health care providers for the period from January 1, 1998 through June 30,
1999. In addition, this Order establishes rules of priority when a filing window
is in effect.
PMID- 10182570
TI - Privacy Act of 1974; system of records--HCFA. Notice of new system of records.
AB - In accordance with the requirements of the Privacy Act of 1974, we are proposing
to establish a new system of records, called "Health Plan Management System
(HPMS),"HHS/HCFA/CHPP, No. 09-70-4004. We have provided background information
about the proposed new system in the Supplementary information section below.
Although the Privacy Act requires only that the "routine uses" portion of the
system be published for comment, HCFA invites comments on all portions of this
notice.
PMID- 10182571
TI - Security and electronic signature standards--HCFA. Proposed rule.
AB - This rule proposes standards for the security of individual health information
and electronic signature use by health plans, health care clearinghouses, and
health care providers would use the security standards to develop and maintain
the security of all electronic individual health information. The electronic
signature standard is applicable only with respect to use with the specific
transactions defined in the Health Insurance Portability and Accountability Act
of 1996, and when it has been determined that an electronic signature must be
used. The use of these standards would improve the Medicare and Medicaid
programs, and other Federal health programs and private health programs, and the
effectiveness and efficiency of the health care industry in general. This rule
would implement some of the requirements of the Administrative Simplification
subtitle of the Health Insurance Portability and Accountability Act of 1996.
PMID- 10182572
TI - Medicare and state health care programs: fraud and abuse; issuance of advisory
opinions by the OIG--HHS. Correction.
PMID- 10182573
TI - Medical use of byproduct material; proposed revision--NRC. Proposal rule.
AB - The Nuclear Regulatory Commission (NRC) is proposing a revision of its
regulations governing the medical use of byproduct material. The proposed rule is
one component of the Commission's overall program for revising its regulatory
framework for medical use. The overall goals of this program are to focus NRC's
regulations on those medical procedures that pose the highest risk to workers,
patients, and the public, and to structure its regulations to be risk-informed
and more performance-based, consistent with the NRC's "Strategic Plan for Fiscal
Year 1997-Fiscal Year 2002". A notice in this issue of the Federal Register
announcing the Commission's proposed revision of its 1979 "Medical use Policy
Statement" for public comment is published elsewhere.
PMID- 10182574
TI - Medical use of byproduct material; draft policy statement--NRC. draft policy
statement.
AB - The Nuclear Regulatory Commission (NRC) is proposing, for formal comment,
revisions of its 1979 policy statement on the medical use of byproduct material.
These proposed revisions are one component of the Commission's overall program,
as previously announced in the Federal Register, for revising its regulatory
framework for medical use, including its regulations that govern the medical use
of byproduct material. The overall goals of this program are to focus NRC
regulation of medical use on those medical procedures that pose the highest risk
and to structure its regulations to be risk-informed and performance-based, where
appropriate, consistent with NRC's "Strategic Plan for Fiscal Year 1970 Fiscal
Year 2002".
PMID- 10182576
TI - Are HMOs off the critical list?
PMID- 10182575
TI - Medicare program; update of ratesetting methodology, payment rates, payment
policies, and the list of covered procedures for ambulatory surgical centers
effective October 1, 1998; extension of comment period--HCFA. Notice of extension
of comment period for proposed rule.
AB - This notice extends the comment period for a proposed rule published in the
Federal Register on June 12, 1998 (63 FR 32290). In that rule we proposed to:
Update the criteria for determining which surgical procedures can be
appropriately and safely performed in an ambulatory surgical center (ASC): Make
additions to and deletions from the current list of Medicare covered ASC
procedures based on the revised criteria; Rebase the ASC payment rates using
cost, charge, and utilization data collected by a 1994 survey of ASCs; Refine the
ratesetting methodology that was implemented by a final notice published on
February 8, 1990 in the Federal Register; Require that ASC payment, coverage, and
wage index updates be implemented annually on January 1 rather than having these
updates occur randomly throughout the year; Reduce requlatory burden; and Make
several technical policy changes. This proposed rule implements requirements of
section 1833(i) (1) and (2) of the Social Security Act. The comment period is
extended for 30 days.
PMID- 10182577
TI - Saving Sierra's health care contract.
PMID- 10182578
TI - Compensation monitor. Executive salaries mostly below $200,000.
PMID- 10182579
TI - Truce! Like it or not, managed care is here to stay. Trust is still thin, but
physicians and plans are learning to collaborate.
PMID- 10182580
TI - Learning together. Truce: a program pairing academic medical institutions with
managed care companies teaches residents how health plans work--and to work with
them.
PMID- 10182581
TI - Making Medicare+Choice work.
PMID- 10182582
TI - Data access technology puts physicians under microscope.
PMID- 10182583
TI - First medical school, then managed care school.
PMID- 10182584
TI - Is medical ethics the same as corporate compliance?
PMID- 10182585
TI - HCFA implementation of Stark II law examines motive in payment review.
PMID- 10182586
TI - Managed care outlook. Physicians underestimate how well they're communicating
with patients.
PMID- 10182587
TI - The art of persuasion.
PMID- 10182588
TI - Relationship management: assessing coalitions, networks, and other workgroups.
PMID- 10182589
TI - Breast center guidance, surveillance and care.
PMID- 10182590
TI - Against consumers.
PMID- 10182591
TI - The digital promise.
PMID- 10182592
TI - Cost-effective systems of care for senior populations.
PMID- 10182593
TI - Malpractice risks and prevention in emergency medicine.
PMID- 10182594
TI - Managed care: the risk of underpricing.
PMID- 10182595
TI - The relationship between cost and quality.
PMID- 10182596
TI - Show me the money, Part III. Barbarians on both sides of the gate.
PMID- 10182597
TI - The survival and prosperity of physician-led networks.
PMID- 10182598
TI - Pharmacoeconomic considerations in rural hospitals.
PMID- 10182599
TI - Growth lessons from Fortune 500 companies.
PMID- 10182600
TI - Viewing health care as an integrated system.
AB - Although still in its early stages, disease management is already proving to be
effective in decreasing health care expenditures by increasing compliance and
normalizing utilization patterns. For the greatest benefit to be realized over
the long term, however, a disease management program must target the 80 percent
of the identified population not yet in the action stage. Only by appropriate
interventions designed to move individuals incrementally from stage to stage will
disease management fulfill its promise of appropriately lowering health care
costs by cutting across the established component system.
PMID- 10182601
TI - Marketplace. New approaches change capitation to meet criticisms.
PMID- 10182602
TI - Perspectives. California task force favors modest measures.
PMID- 10182603
TI - Implementing health status measurements.
PMID- 10182604
TI - Measurement tools: what's available, how to choose.
PMID- 10182605
TI - JNC VI targets prevention and risk stratification.
PMID- 10182606
TI - Building a quality future.
AB - How can healthcare leaders stay ahead of the curve? What can they do to see what
the future holds and to secure a place for their employees and their
organizations? They must begin doing today what they need to do to survive
tomorrow. Furthermore, they must take wise action today or there will be no
tomorrow. This article looks into the future and connects it with what we must
see and do today. The article begins with a glimpse of the future and with an
exploration of what people really want from health and healthcare. Next, it
examines what appear to be inexorable megatrends and healthcare trends that are
sweeping through society. This leads us to consider the quality and value
imperatives that must be faced to secure a stake in the healthcare delivery. We
will discuss a model for managing care for individual patients and small
populations by focusing on where patients, populations, and caregivers meet--at
the front lines of patients care. We conclude with some advice on how to build
sustainable organizations by exploiting the inevitable.
PMID- 10182607
TI - The role of senior leaders in driving rapid change.
PMID- 10182608
TI - Building healthcare quality: if the future were easy, it would be here by now.
PMID- 10182610
TI - New York City. Michael Callen-Audre Lorde Community Health Center. Thanhauser and
Esterson Architects.
PMID- 10182609
TI - Patients, populations, and caregivers: opportunities and challenges at the
intersection.
PMID- 10182611
TI - New York City. Special Suites, Memorial Sloan Kettering Cancer Center. Perkins
Eastman Architects.
PMID- 10182612
TI - Los Angeles. Revlon/UCLA Breast Center. Israel Callas Chu Shortridge.
PMID- 10182614
TI - Chicago. Trinity Hospital Pediatric Unit. HDR Architecture, Inc.
PMID- 10182613
TI - Chicago. Child Life Center, Children's Memorial Hospital. VOA Associates Inc.
PMID- 10182615
TI - Newport Beach, CA. Harry and Grace Steele Children's Center, Orange Coast
College. Taylor and Associates Architects.
PMID- 10182616
TI - Workforce planning. Your country needs you.
AB - Shortage of nurses is a long-standing problem which was the subject of official
inquiries long before the launch of the NHS. There has been persistent inertia
about acting on the recommendations of these reports. Despite a continuing
increase in activity rates, the number of nurses in the NHS has remained largely
static for a decade. Another 5,000 will be needed by 2015. The UK should use its
capacity for centralised planning to tackle the issue.
PMID- 10182617
TI - Waiting lists. Listless feeling.
AB - New Zealand is attempting to replace waiting lists with a booking system for
elective surgery such as hip replacements, cataract removal and heart bypass
operations, and medical procedures. The propose system would only accept for
treatment those patients assessed as likely to gain the greatest benefit.
Purchasers were originally instructed to implement the system by this month. This
has now been postponed until July 1999. The proposals are being opposed by
clinicians on the basis that, in some cases, they would rule out 30 per cent of
patients from treatment.
PMID- 10182618
TI - Prescribing. The price is right.
PMID- 10182619
TI - The shape of things to come.
AB - Geographical boundaries have always been significant in the NHS. The planned
reconfiguration of NHS regions including the establishment of a pan-London
region, will have consequences across the whole of the service. The proposed
changes will strengthen the power of central government in terms of policy and
resource allocation. It is not clear whether boundary changes have any impact on
patient care. Boundary changes create pressure for further reorganizations.
PMID- 10182620
TI - Community health councils. Voices of dissent.
PMID- 10182621
TI - Mental health. Doorstep delivery.
AB - A 24-hour home care team for people with severe mental illness has led to a
reduction in inpatient stays and reduced service costs, according to a controlled
evaluation. The 24-hour availability was popular with users. Home treatment
should not be seen as an exclusive alternative to inpatient care. Admission is
essential in some cases.
PMID- 10182622
TI - 6 ways to organize your practice.
PMID- 10182623
TI - How we wrote our own managed-care success story.
PMID- 10182624
TI - Roe vs. Wade at 25: the tough questions linger.
PMID- 10182625
TI - The Feds take aim at fraud and abuse.
PMID- 10182626
TI - Will Washington rein in the fraud police?
PMID- 10182627
TI - Mergers & acquisitions. HMO consolidations can mean big bucks for their CEOs.
PMID- 10182628
TI - How groups are profiting from case management.
PMID- 10182629
TI - Lab industry and others take on False Claims Act.
PMID- 10182630
TI - Needlesticks: who pays the price when costs are cut on safety.
AB - Here is a syringe whose spring-loaded needle automatically retracts into the
barrel of the syringe almost quicker than the eye can register--If you've never
seen one, you're not alone. Despite the prevalence of needles engineered with
safety features to prevent needlesticks, few organizations are using them. The
reasons why go far beyond the expense of the syringe.
PMID- 10182631
TI - Amplified DNA technology: where does it fit in?
PMID- 10182632
TI - As others see us, Part 2. Goals and the annual report: a system for performance
evaluation.
AB - This systematic approach to an annual performance report can show that laboratory
professionals are active outside the physical laboratory as a vital part of the
healthcare team. The annual report also provides an opportunity to show the many
dimensions of clinical laboratory science and presents evidence of the
multifaceted role of the laboratory manager. The annual report shows that
employees can be self-directed and creative in goal setting and in achieving
goals. In addition, the annual report is helpful should a laboratorian decide to
apply for a promotion or other position. Also, the annual report documents a
track record and demonstrates abilities and qualifications to prospective
employers for expanded careers outside the laboratory. But most importantly, the
annual report can be used as a road map for insight into professional growth and
development.
PMID- 10182633
TI - The central laboratory: who needs it?
AB - A central lab can provide substantial savings in personnel and procurement costs
while promoting improvements in service. Activities integral to this process are
coordinating purchasing, implementing common processes, identifying key
facilities, and using a common management information system.
PMID- 10182634
TI - Laboratory consolidation. Minimizing the angst and aggravation.
AB - In response to decreasing payment structures, many labs have begun considering
those programs that strike fear in the hearts of employees everywhere-
consolidation. To avoid whispers of layoffs, salary cuts, and scheduling
disasters that become grist for the rumor mill, try constant communication and a
structured management.
PMID- 10182635
TI - 'Zero-tolerance' for abuse and neglect.
PMID- 10182636
TI - Distinguishing Features Award. Design that makes a difference.
PMID- 10182637
TI - Keynoter Stephen Covey discusses principle-centered leadership.
PMID- 10182638
TI - Plugging into electricity deregulation.
PMID- 10182639
TI - Avoiding wrongful discharge.
PMID- 10182640
TI - Therapy caps pose threat to residents.
PMID- 10182641
TI - Pain management found lacking.
PMID- 10182642
TI - Drug-resistant pneumonia alarms officials.
PMID- 10182643
TI - Assisted living goes high tech.
PMID- 10182644
TI - National Hospital Ambulatory Medical Care Survey: 1996 emergency department
summary.
AB - OBJECTIVES: This report describes ambulatory care visits to hospital emergency
departments in the United States. Statistics are presented on selected patient
and visit characteristics. METHODS: The data presented in this report were
collected from the 1996 National Hospital Ambulatory Medical Care Survey
(NHAMCS). NHAMCS is part of the ambulatory care component of the National Health
Care Survey that measures health care utilization across various types of
providers. NHAMCS is a national probability survey of visits to hospital
emergency and outpatient departments of non-Federal, short-stay, and general
hospitals in the United States. Sample data were weighted to produce annual
estimates. RESULTS: During 1996, an estimated 90.3 million visits were made to
hospital emergency departments (ED's) in the United States, about 34.2 visits per
100 persons. Persons 75 years and over had the highest rate of emergency
department visits. There were an estimated 34.9 million injury-related emergency
department visits during 1996, or 13.2 visits per 100 persons. There were 110,000
visits related to injuries caused by firearms, including 73,000 visits for
gunshot wounds. Almost one-fifth of the injury visits were work-related for
persons 18-64 years of age. Almost four-fifths of the ED visits involved
medication therapy. Pain relief drugs accounted for almost 30 percent of the
medications mentioned. Acute upper respiratory infection was the leading illness
related diagnosis for ED visits.
PMID- 10182645
TI - National Hospital Ambulatory Medical Care Survey: 1996 outpatient department
summary.
AB - OBJECTIVE: This report describes ambulatory care visits to hospital outpatient
departments in the United States. Statistics are presented on selected patient
and visit characteristics. METHODS: The data presented in this report were
collected from the 1996 National Hospital Ambulatory Medical Care Survey
(NHAMCS). NHAMCS is part of the ambulatory care component of the National Health
Care Survey that measures health care utilization across various types of
providers. NHAMCS is a national probability survey of visits to hospital
outpatient and emergency departments of non-Federal, short-stay, and general
hospitals in the United States. Sample data were weighted to produce annual
estimates. RESULTS: During 1996, an estimated 67.2 million visits were made to
hospital outpatient departments in the United States, about 25.4 visits per 100
persons. Overall, visits rates did not vary by age. Females and black persons had
higher rates of visits than males and white persons, respectively. There were an
estimated 6.8 million injury--related outpatient department visits during 1996.
PMID- 10182646
TI - National Ambulatory Medical Care Survey: 1996 summary.
AB - OBJECTIVES: This report describes ambulatory care visits made to physician
offices within the United States. Statistics are presented on selected physician,
patient, and visit characteristics of ambulatory care visits. METHODS: The data
presented in this report were collected from the 1996 National Ambulatory Medical
Care Survey (NAMCS). The NAMCS is part of the ambulatory care component of the
National Health Care Survey, which measures health care utilization across
various types of providers. The NAMCS is a national probability sample survey of
visits to office-based physicians in the United States. Sample data are weighted
to produce annual estimates. RESULTS: During 1996, an estimated 734.5 million
visits were made to physician offices in the United States, an overall rate of
2.8 visits per person. One quarter of the NAMCS visits were made to general and
family physicians, which was significantly higher than the other 13 specialties.
Persons 75 years and over had the highest rate of physician office visits, 6.3
visits per person. Females had a significantly higher rate of visits to
physicians offices than males did overall, as did white persons compared with
black persons. Of all visits made to these offices in 1996, 87 percent were
covered by some form of insurance, and 8.7 percent were paid "out-of-pocket."
There were an estimated 87.6 million injury-related visits during 1996, or 33.1
visits per 100 persons. Three-quarters of these visits were for unintentional
injuries.
PMID- 10182647
TI - Ambulatory surgery in the United States, 1995.
AB - OBJECTIVES: This report presents estimates of surgical and nonsurgical procedures
performed on an ambulatory basis in hospitals and freestanding ambulatory surgery
centers in the United States during 1995. Data are presented by types of
facilities, age, sex, and geographic region. Major categories of procedures and
diagnoses are shown by age, sex, and region. METHODS: The estimates are based on
data collected from the 1995 National Survey of Ambulatory Surgery conducted by
the National Center for Health Statistics. The 1995 data were abstracted from
122,000 medical records in 489 hospitals and freestanding ambulatory surgery
centers.
PMID- 10182648
TI - An overview of home health and hospice care patients: 1996 National Home and
Hospice Care Survey.
AB - OBJECTIVE: This report presents numbers and percents of home health and hospice
care agencies, their current patients, and their discharges. Agency
characteristics include type of ownership, region, certification, location, and
affiliation. Patient and discharge characteristics include age, sex, race,
marital status admission diagnoses, and procedures. METHODS: The data used for
this report are from the National Center for Health Statistics' 1996 National
Home and Hospice Care Survey. This is a sample survey through which data are
collected on the use of home health and hospice care agencies in the United
States. RESULTS: During 1996, there were an estimated 2.5 million current
patients and 8.2 million discharges from 13,500 home health and hospice care
agencies in the United States. The agencies tended to be proprietary, certified
by Medicare and Medicaid as a home health agency, and located in a metropolitan
statistical area. Almost half were part of a chain or group of agencies. The home
health and hospice care patients and discharges tended to be 65 years of age and
over, female, white, and married or widowed. The most common diagnoses for home
health care patients were diseases of the circulatory system, and the most common
diagnoses for hospice care patients were malignant neoplasms. About a third of
the home health care patients and about a fifth of the hospice care patients had
a surgical or diagnostic procedure related to their admission for care. The most
common procedures for home health care patients were operations on the
musculoskeletal system, and for hospice care patients they were miscellaneous
diagnostic and therapeutic procedures.
PMID- 10182649
TI - Transfusion oversight out of the bag.
PMID- 10182650
TI - A race to rework lab space.
PMID- 10182651
TI - Guidelines take shape on ANA, gammopathy testing.
PMID- 10182652
TI - Hemochromatosis.
PMID- 10182653
TI - Upgrade or migrate.
PMID- 10182654
TI - Providing enhanced value through integrated data.
PMID- 10182655
TI - Automation: the key to repricing PPO claims.
PMID- 10182657
TI - Survival of physician self-referral to physical therapy centers with physician
held owner interest.
AB - Physician ownership of ancillary services has grown during recent years as a
means of expanding financial security--as well as providing convenient access for
patients and physicians. As these investments have spread, so too have concerns
expressed by professional organizations and state and federal regulatory
commissions. This professional paper will explore the historical perspective of
federal and state regulatory impacts regarding physician ownership of ancillary
services (specifically physical therapy centers), will develop a view of
yesterday's regulatory impacts and help outline the necessity of change for
tomorrow.
PMID- 10182656
TI - Physician compensation: the dark side.
AB - As with any medical group, physician compensation can be hard to handle-
especially between senior and young physicians. In this case study, the author
finds that although there are many options in compensation, so too are there
other considerations. This article reflects the options, advantages,
disadvantages and conclusions this group reached regarding physician
compensation.
PMID- 10182658
TI - Merger acquisition or independence--small group decision--large group impact.
AB - As this group practice looked to the future, two alternatives were considered-
remain independent or merge with another entity. Remaining independent, although
desirable, would be extremely difficult, so this group looked for a mutually
beneficial affiliation. This case study details the beginning-to-end affiliation
process--from seeking potential partners to signing the papers: the keys to
success and potential dealbreakers.
PMID- 10182659
TI - Planning for the future: moving to the multispecialty group organizational
structure.
AB - Physicians in a Southeastern community were finding themselves ill equipped to
deal with many of the requirements of insurance companies, state governments and
managed care organizations. One medical practice was considering moving toward
becoming a multispecialty group and adding physicians to keep with their
objective of having a "growing practice." This case study is centered around the
efforts of the physicians' involvement in the strategic planning process of
growing their practice.
PMID- 10182660
TI - Managed care: competitive strategies for academic medical centers.
AB - For academic medical centers to get from where they are to where they need to be,
their traditional clinical services paradigm must change in a frame-breaking, re
engineered, revolutionary way. The change must be real, as the market place will
recognize impostors, and it must be led by a strongly committed executive
leadership team. This professional paper will show that once accomplished,
academic medical centers will most likely acquire the "competitive advantage"
needed to win their rightful position in the future health care marketplace.
PMID- 10182661
TI - Development of a computerized physician credentialing database.
AB - This case study defines the concerns, options and solutions to developing an
automated central repository and database. The database would include physicians'
credentialing information that, in turn, will make the managed care
organizations' application process more manageable and effective, thereby
retaining and/or increasing patient volume and revenue.
PMID- 10182662
TI - Strategic implications of a "paperless" information system.
AB - The movement of the typical medical practice toward increased size, dispersed
operations and formalized affiliations with hospitals, insurance companies and
other providers has exacerbated the problems of information management.
Antiquated information systems have become a serious impediment to efficient
operations in many medical practices. This professional paper describes the
advantages, obstacles and necessity of implementing a comprehensive electronic
information system.
PMID- 10182663
TI - Malpractice carriers: a selection process.
PMID- 10182664
TI - Developing a physician recruitment support arrangement with a hospital.
AB - Historically, hospitals have been willing to provide assistance with recruitment
efforts to private physicians and physician groups. However, new federal
regulations demand a more structured approach. Current legislative directives
provide restrictions, but give little guidance for developing arrangements with
private individuals for recruiting physicians. This professional paper looks at
ways to establish a sound recruiting arrangement with a hospital. As well, this
paper describes the benefits of a properly structured arrangement and the dangers
involved if the proper structure and documentation are not developed.
PMID- 10182665
TI - Capitation: friend or foe?
PMID- 10182666
TI - The emergency department under managed care: exploring an alternative model.
AB - An obvious emphasis by managed care organizations is to limit emergency
department care to only the most emergent patients. The result? A "lean & mean"
department. However, another approach would be to encourage emergency department
care--it offers more comprehensive services to both the managed care organization
and the patient. And this professional paper explains how it's possible.
PMID- 10182667
TI - Medical group practice applications for HEDIS: reality or myth?
AB - Through administrative review or random sample, health plan statisticians have
ventured into group practice to collect indices that attempt to assess and
measure quality. Yet group practice, as a means for assisting in the data
collection processes of HEDIS, has had little participation in its development.
This professional paper seeks to explore ways in which a group practice can play
an important part in some area of HEDIS measurement and data collection.
PMID- 10182668
TI - Single specialty capitation: a case study in obstetrics and gynecology.
AB - Faced with a declining maternity census and shrinking market share,
representatives of the hospital and physicians developed a proposal to
subcontract their Ob/Gyn services to a large multispecialty group. This case
study reviews the steps taken to subcontract the group and the lessons learned
along the way.
PMID- 10182670
TI - Rural health care for sparsely populated regions: an emergency medicine delivery
model.
AB - Emergency medical care has long been a matter of serious concern and difficulty,
both for patients living in rural areas and the physicians and medical personnel
who have served these areas. This paper provides an update of the drastic
improvements in rural health care made possible by today's technology.
PMID- 10182669
TI - Ethics of managed care: clinical and administrative implications for medical
group practices.
AB - This professional paper reviews several current ethical dilemmas: situations that
may compromise the patient's dignity; a social thrust towards "universal" care
that has left providers in a no-man's land of "to treat or not to treat"
decisions; financial models which reduce available services, or that directly
incentivize practices to withhold care. Behind each of these issues are values
that managers [and physicians] must consider if they are to protect and improve
the quality of health care.
PMID- 10182671
TI - Managed care contracting in an academic environment.
AB - Issues related to administering managed care in the teaching environment of an
academic medical practice may be drastically different than the same types of
issues in a typical medical practice. This paper is an overview of those specific
discrepancies and how they must be dealt with.
PMID- 10182672
TI - The primary care practice in transition: strategies for managing the evolution
from fee for service to prepaid care.
AB - Changing old thought patterns, habits and preconceived notions is not always easy
in today's ever-changing world of health care practice and administration. This
paper offers advice on solutions pertaining to implementation of prepaid care
programs.
PMID- 10182673
TI - Functionality of a nurse practitioner within a hematology/oncology group
practice.
AB - As more and more medical practice organizations consider the addition of a Nurse
Practitioner on staff, many fears, concerns, and questions arise within the
organization, from both staff and patients. This paper addresses those issues and
provides suggestions on how to manage the transition.
PMID- 10182674
TI - Health care electronic data interchange: a solution for the future.
PMID- 10182675
TI - How to increase efficiency with a cycle time reduction check sheet.
PMID- 10182676
TI - From check-boxes to bytes: one hospital's transition process.
PMID- 10182677
TI - Comparative analysis software: a powerful tool for health care.
PMID- 10182678
TI - Internet commerce. Is it only a dream?
PMID- 10182679
TI - Stats are OK--but trust your gut.
PMID- 10182680
TI - Infection control special report. After the needlestick.
PMID- 10182681
TI - Supply pricing update.
PMID- 10182682
TI - Sew what? Hospital makes linens from scratch.
PMID- 10182683
TI - HMOs under the knife. The capital races to crack down on managed care.
PMID- 10182684
TI - Nursing-home verdicts: there's guilt all round. Boomers sue on their parents'
behalf, and win big.
PMID- 10182685
TI - The home health industry faces mounting allegations of fraud.
PMID- 10182686
TI - Physician-assisted suicide and euthanasia's impact on the frail elderly:
something to think about.
PMID- 10182687
TI - The Balanced Budget Act of 1997--what it means for home care providers and
beneficiaries.
PMID- 10182688
TI - Physician-assisted suicide and euthanasia's impact on the frail elderly: a
physician's reply.
PMID- 10182689
TI - Physician-assisted suicide and euthanasia's impact on the frail elderly: a social
worker's response.
PMID- 10182690
TI - Physician-assisted suicide and euthanasia's impact on the frail elderly: the
perspective of a hospice nurse.
PMID- 10182691
TI - Radiology devices; classifications for five medical image management devices;
correction--FDA. Final rule; correction.
AB - The Food and Drug Administration (FDA) is correcting a final rule that appeared
in the Federal Register of April 29, 1998 (63 FR 23385). The document classified,
along with other devices, the medical image storage device and medical image
communications device. These devices were classified into Class I and were
exempted from the requirement of premarket notification when they do not use
irreversible data compression. The document was published with an incomplete
device identification and description of the conditions for exemption from
premarket notification. This document corrects those errors.
PMID- 10182692
TI - Additional disability or death due to hospital care, medical or surgical
treatment, examination, or training and rehabilitation services--VA. Final rule.
AB - This document amends the Department of Veterans Affairs (VA) adjudication
regulations concerning awards of compensation or dependency and indemnity
compensation for additional disability or death due to VA hospital care, medical
or surgical treatment, examination, or training and rehabilitation services.
Under this final rule, benefits are payable for additional disability or death
caused by VA hospital care, medical or surgical treatment, or examination only if
VA fault or "an event not reasonably foreseeable" proximately caused the
disability or death. Benefits are also payable for additional disability or death
proximately caused by VA's provision of training and rehabilitation services.
This final rule is necessary to reflect Congress' recent amendment of 38 U.S.C.
1151, the statutory authority for such benefits.
PMID- 10182693
TI - Publication of OIG compliance program guidance for clinical laboratories--HHS.
Notice.
AB - This Federal Register notice sets forth the OIG's recently-issued Compliance
Program Guidance for Clinical Laboratories. The OIG had previously developed and
published a model compliance plan for the clinical laboratory industry on March
3, 1997. This Compliance Program Guidance for Clinical Laboratories is intended
to be more consistent with compliance program guidances issued by the OIG with
respect to the hospital industry and to home health agencies, and serves to
clarify various aspects of the original model plan. As with previously-issued
compliance program guidances, we believe that the development of this guidance
for clinical laboratories will continue as a positive step towards promoting a
higher level of ethical and lawful conduct throughout the entire health care
community.
PMID- 10182694
TI - Medical device reporting: manufacturer reporting, importer reporting, user
facility reporting, distributor reporting--FDA. Direct final rule; withdrawal.
AB - The Food and Drug Administration (FDA) published in the Federal Register of May
12, 1998, a proposed rule (63 FR 26129) and a direct final rule (63 FR 26069) to
implement amendments to the medical device reporting provisions of the Federal
Food, Drug, and Cosmetic Act, as amended by the FDA Modernization Act of 1997
(FDAMA). The comment period closed July 27, 1998. FDA is withdrawing the direct
final rule because the agency received significant adverse comment.
PMID- 10182696
TI - Announcement of OMB approval for reporting and disclosure requirements in the
final rule with comment period for Organ Procurement and Transplantation Network-
HRSA.
PMID- 10182695
TI - Medical device warning letter draft pilot; availability--FDA. Notice.
AB - The Food and Drug Administration (FDA) is planning to initiate a pilot program
involving the medical device industry that is a continuation of the "medical
device industry initiatives." This draft pilot concerns the issuance of warning
letters for quality system, premarket notification submission (510(k)), and
labeling violations. This draft pilot is intended to optimize resource
utilization, enhance communication between industry and FDA, and provide firms
with incentives to promptly correct violations or deficiencies. The draft pilot
includes eligibility criteria and procedures for the issuance of warning letters
and will not be implemented until after the public comment period has expired.
PMID- 10182697
TI - Federal Employees Health Benefits Program: contributions and withholdings--OPM.
Interim regulations with request for comments.
AB - The Office of Personnel Management (OPM) is issuing interim regulations to
describe procedures for OPM's annual determination of the weighted average of
subscription charges in effect for self only and for self and family enrollments
under the Federal Employees Health Benefits (FEHB)Program. The determinations are
a requirement under recent amendments to the FEHB law which authorize a new
Government contribution toward FEHB enrollment charges effective with the
contract year beginning in January 1999, which generally pays 72 percent of the
weighted average of subscription charges.
PMID- 10182698
TI - Amended economic impact analysis of final rule requiring use of labeling on
natural rubber containing devices--FDA. Final rule; amended economic analysis
statement.
AB - The Food and Drug Administration (FDA) is issuing an amended economic analysis
statement relating to a final rule that published in the Federal Register of
September 30, 1997 (62 FR 51021), requiring labeling statements concerning the
presence of natural rubber latex in medical devices. This rule was issued in
response to numerous reports of severe allergic reactions and deaths related to a
wide range of medical devices containing natural rubber. The final rule becomes
effective on September 30, 1998. In order to allow further comment on the
economic impact of the September 30, 1997, final rule, FDA published in the
Federal Register of June 1, 1998, an amended economic impact statement, including
an amended initial regulatory flexibility analysis (IRFA) that it prepared under
the Regulatory Flexibility Act (RFA), as amended by the small Business Regulatory
Enforcement and Fairness Act (SBREFA). After considering comments submitted in
response to the June 1, 1998, amended economic analysis statement, FDA is issuing
the amended final economic impact statement, including an amended final
regulatory flexibility analysis.
PMID- 10182700
TI - Federal employees health benefits program: effective dates--OPM. Proposed rule.
AB - The Office of Personnel Management (OPM) is issuing proposed regulations to
change the existing Federal Employees Health Benefits (FEHB) Program regulations
concerning the effective date for new enrollments made by employees during the
annual open season. These regulations would also change the effective date of
open season changes in enrollment made by employees, annuitants, former spouses
and individuals enrolled under the temporary continuation of coverage (TCC)
provisions of FEHB law. The proposed regulations would standardize the effective
date of most of these new enrollments or changes in enrollment. This would make
it easier for employing offices and health plan carriers to administer the
Program and reduce the potential for error in determining effective dates.
PMID- 10182699
TI - Natural rubber-containing medical devices; user labeling; cold seal adhesives
partial stay--FDA. Final rule.
AB - The final rule for user labeling requirements for natural rubber-containing
medical devices, 21 CFR 801-437, was published on September 30, 1997, and becomes
effective on September 30, 1998. The Food and Drug Administration (FDA) is adding
a note to that rule to stay, for 270 days from the effective date, paragraphs (f)
and (g) as those final rule requirements relate to device packaging that uses
"cold seal" adhesives. Labeling changes required by other paragraphs of this
final rule must be incorporated in the labeling of devices distributed after
September 30, 1998, even if the devices are packaged in "cold seal" packages.
Device packaging that uses natural rubber only on adhesives contained in the
flaps of device packaging is not considered subject to the rule. Manufacturers of
devices packaged with "cold seal" adhesives may, if necessary, submit a petition
for an extension of the 270-day stay.
PMID- 10182701
TI - Organization, functions, and delegations of authority: HIV/AIDS prevention-
International Research and Support Division--CDC.
PMID- 10182703
TI - Designation of medically underserved populations and health professional shortage
areas--HRSA. Proposed rules.
AB - The rules proposed below would consolidate the processes for designating
medically underserved populations (MUPs) and health professional shortage areas
(HPSAs), designations that are used in several DHHS programs. The purpose is to
improve the way underserved areas are designated by incorporating up-to-date
measures of health status and access barriers and eliminating inconsistencies and
duplication of effort. The intended effect is to reduce the effort and data
burden on States and communities by simplifying and automating the design process
as much as possible, while maximizing the use of technology. The proposed rules
involve major changes to both the MUP and the primary care HPSA designation
criteria, which have the effect of making primary care HPSAs a subset of the
MUPs. No changes are proposed with respect to the criteria for designating dental
and mental health HPSAs. Podiatric, vision care, pharmacy, and veterinary care
HPSA designations would be abolished under the rules proposed below.
PMID- 10182702
TI - Verification of eligibility for public benefits--INS. Correction.
PMID- 10182704
TI - Health care programs: fraud and abuse; revised OIG exclusion authorities
resulting from Public Law 104-191--OIG. Final rule.
AB - This final rule addresses revisions to the OIG's administrative sanction
authorities to comport with sections 211, 212 and 213 of the Health Insurance
Portability and Accountability Act (HIPAA) of 1996, along with other technical
and conforming changes to the OIG exclusion authorities set forth in 42 CFR parts
1000, 1001, 1002 and 1005. These revisions serve to expand the scope of certain
basic fraud authorities, and revise and strengthen the current legal authorities
pertaining to exclusions from the Medicare, Medicaid and all other Federal health
care programs.
PMID- 10182705
TI - Biological products regulated under Section 351 of the Public Health Services
Act; implementation of biologics license; elimination of establishment license
and product license; correction--FDA. Proposed rule; correction.
AB - The Food and Drug Administration (FDA) is correcting a proposed rule that
appeared in the Federal Register of July 31, 1998 (63 FR 40858). The document
proposed to amend the biologics regulations to eliminate references to
establishment licenses and product licenses for all products regulated under the
Public Health Services Act. The document published with an incorrect address.
This document corrects that error.
PMID- 10182706
TI - Health care programs: fraud and abuse; revised OIG sanction authorities resulting
from Public Law 105-33--OIG. Notice of proposed rulemaking.
AB - This rulemaking proposes revisions to the OIG's exclusion and civil money penalty
authorities set forth in 42 CFR parts 1001, 1002 and 1003, resulting from the
Balanced Budget Act of 1997, Public Law 105-33. These proposed revisions are
intended to protect and strengthen Medicare and State health care programs by
increasing the OIG's anti-fraud and abuse authority through new or revised
exclusion and civil money penalty provisions.
PMID- 10182708
TI - Statement of organization, functions, and delegations of authority--Center for
Managed Care--HRSA.
PMID- 10182707
TI - Proposed vaccine information materials for hepatitis B, Haemophilus influenzae
type b (Hib), Varicella (chickenpox), and measles, mumps, rubella (MMR) vaccines-
CDC. Notice with comment period.
AB - Under the National Childhood Vaccine Injury Act (42 U.S.C. section 300aa-26), CDC
must develop vaccine information materials that health care providers are
required to give to patients/parents prior to administration of specific
vaccines. CDC seeks written comment on proposed new vaccine information materials
for hepatitis B, Haemophilus influenzae type b, and Varicella vaccines, and
revised vaccine information materials for measles, mumps, rubella (MMR) vaccines.
PMID- 10182709
TI - Federal Employees Health Benefits Program, Medically Underserved Areas for 1999-
OPM. Notice of medically underserved areas for 1999.
AB - The Office of Personnel Management has completed its annual calculation of the
States that qualify as Medically Underserved Areas under the Federal Employees
Health Benefits (FEHB) Program for the calendar year 1999. This is necessary to
comply with a provision of FEHB law that mandates special consideration for
enrollees of certain FEHB plans who receive covered health services in states
with critical shortages of primary care physicians. Accordingly, for calendar
year 1999, OPM's calculations show that the following States are Medically
Underserved Areas under the FEHB Program: Alabama, Idaho, Louisiana, Mississippi,
New Mexico, North Dakota, South Carolina, South Dakota, and Wyoming. West
Virginia has been removed from the 1998 list, and Idaho and North Dakota have
been added.
PMID- 10182710
TI - Uniform administrative requirements for grants and agreements with institutions
of higher education, hospitals, other non-profit, and commercial organizations-
Department of Commerce. Interim final rule.
AB - This interim final rule implements the revisions to the Office of Management and
Budget (OMB) Circular A-110, "Uniform Administrative Requirements for Grants and
Agreements With Institutions of Higher Education, Hospitals, and Other Non-Profit
Organizations" which was published in the Federal Register on November 29, 1993.
The revised Circular was developed by an interagency task force for
governmentwide use in a model rule format to facilitate regulatory adoption by
executive departments and agencies. In the published revised Circular, OMB
specified as "required action" that Federal agencies responsible for awarding and
administering grants and other agreements to recipients described therein, shall
adopt the language of the Circular unless other provisions are required by
Federal statute or exceptions or deviations are approved by OMB. This interim
final rule adopts the provisions of the Circular and its language to the maximum
extent feasible. However, minor changes were made to update the procedures,
clarify the language, and make the language apply specifically to the DoC and its
operating units. No changes are intended to deviate from the substance of
Circular A-110. The Circular covers both grants and cooperative agreements made
by Federal agencies and subawards, unless sections of the Circular specifically
exclude subrecipients from coverage. Consistent with guidance provided in the
Circular, DoC will apply its provisions to grants and agreements with
institutions of higher education, hospitals, other nonprofit, and commercial
organizations. The provisions of the interim final rule will also apply to
foreign governments, organizations under the jurisdiction of foreign governments,
and international organizations when appropriate.
PMID- 10182711
TI - Employee theft in the nursing home.
PMID- 10182712
TI - 21 ways to invite employee theft.
PMID- 10182713
TI - Equip your workplace with tools to prevent workplace violence.
PMID- 10182714
TI - Provider sponsored organizations: new opportunities for long-term care providers.
PMID- 10182715
TI - Reducing turnover through ownership.
PMID- 10182716
TI - Changing for today's work force.
PMID- 10182718
TI - HCFA reconsiders, delays implementing consolidated billing rule.
PMID- 10182719
TI - Administrators are the gatekeepers of quality.
PMID- 10182717
TI - Smart planning turns aging building into an assisted living showcase.
PMID- 10182721
TI - Hospitalists reduce LOS, slash costs in academic medical center.
AB - San Francisco-based Moffitt-Long Hospital introduced a "managed care service" led
by hospitalists who practice and teach cost-effective, evidence-based medicine.
Hospitalists can significantly reduce costs and length of stay in an academic
setting if they get involved early and steer the trajectory of inpatient care.
PMID- 10182720
TI - Pharmacist-led anticoagulation clinics reap big rewards.
PMID- 10182722
TI - The wired health system: telemedicine comes of age.
AB - Telemedicine is no longer pie-in-the-sky technology, but already at work saving
hefty sums of money and improving care in the clinical setting. Through a cable
television system in Kansas, nurse practitioners are able to see up to four times
as many patients as is possible with in-person home care visits. And at Boston's
Beth Israel-Deaconess Medical Center, premature babies are monitored by a device
that works over the Internet, avoiding the $2,000 per day cost of the neonatal
ICU.
PMID- 10182723
TI - Coordinated system of care cuts costs, maintains quality for persons with AIDS.
AB - Coordinated HMO care reduces costs for patients with AIDS. Although HMOs get a
bad rap, a surprising study from Boston University found that a comprehensive
system of managed care can do a better job of avoiding hospitalization and
reducing health care costs than traditional fee-for-service plans--without
negatively impacting patient satisfaction, health status, or level of function.
PMID- 10182724
TI - Clinical quality monitoring software identifies problems, reduces costs in ICU.
PMID- 10182725
TI - Bar code labeling replaces frequently entered keystrokes in microbiology lab.
PMID- 10182726
TI - Breath-actuated inhaler uses 23% less medication.
PMID- 10182727
TI - The Balanced Budget Act: effects on home care beneficiaries and providers.
AB - The Balanced Budget Act of 1997 (BBA 97) requires major changes in the way
Medicare reimburses home care agencies. Two independent organizations analyzed
the effects of the BBA 97 on home care; the analyses reveal no surprises. The new
policies give agencies incentives to reduce their volume of care; as a result,
high-use patients are likely to suffer most. This tightening of payments and the
new incentives may lead to adverse effects on both access to and quality of care.
PMID- 10182728
TI - Bipartisan Commission: working to preserve Medicare's future.
AB - The future of Medicare is uncertain. With a pressing need to address the
potential crisis ahead, President Clinton appointed a National Bipartisan
Commission on the Future of Medicare to examine issues and develop
recommendations that address current challenges.
PMID- 10182729
TI - Medicare choices.
AB - There are new choices for Medicare beneficiaries, and individuals may be confused
about what is available to them. Home care providers who understand these choices
can be valuable resources to clients as well as to colleagues.
PMID- 10182730
TI - The changing face of long-term care.
AB - When it comes to long-term care insurance, most people think of elderly clients.
Providers who understand the benefits of this type of insurance can suggest this
option to individuals to ensure that they can remain at home.
PMID- 10182731
TI - Preventing revenue loss by complying with Medicare regulations.
AB - Educating staff, performing billing audits, and appealing claim denials can help
agencies ensure compliance with Medicare regulations and prevent loss of revenue.
By preparing in advance, agencies ensure a smoother ride through (what are quite
often) turbulent investigations.
PMID- 10182732
TI - Using activity-based management to control costs & achieve organization goals.
AB - Activity-based management (ABM) is a management process that focuses on improving
costs and outcomes. It derives useful information based on the way people think
(their activities) rather than traditional expense categories. ABM supports
outcomes, quality, teams, re-engineering, empowerment, and continuous
improvement. It is a process that providers may want to adopt in light of new
Medicare reimbursement practices.
PMID- 10182733
TI - Productivity: survival tools for the fittest.
AB - A slight change in an agency's productivity can significantly affect the bottom
line. Thus, it is in agency's best interest to first determine current levels of
productivity and then track it on an ongoing basis. The ability to continually
measure the productivity of an entire organization will be an essential tool for
surviving the transition from cost-based reimbursement to prospective payment.
PMID- 10182734
TI - Home care does not make it easy--it makes it possible.
PMID- 10182735
TI - The secret door to your agency.
PMID- 10182736
TI - Victims no more: preventing home care aide abuse.
AB - Home care aides are especially susceptible to abuse because of their unique
workplace situation. It's up to their employers--the home care agencies--to take
deliberate steps to prevent on-the-job abuse. The aides, nurses, and supervisors
of the home care team also play an important role in keeping care situations safe
for all involved.
PMID- 10182737
TI - Reduce home care aide turnover: give aides real jobs.
AB - What do home care aides want even more than a raise? Consistent, full-time work
hours. That's what one agency found out in its attempt to decrease employee
turnover. There are other steps agencies can take, too, to keep their aides
coming back.
PMID- 10182738
TI - Medical savings accounts: it's deja vu all over again.
PMID- 10182739
TI - Meeting customer expectations for medical intranets.
PMID- 10182740
TI - Negotiating roadblocks to IDS-physician equity joint ventures.
AB - Integrated delivery systems (IDSs) may find that forming an equity joint venture
relationship with a physician group practice is the best way to integrate
physicians into their networks. IDSs have a choice between two basic equity
structures: affiliated group practice, in which a management services
organization (MSO) handles all practice management infrastructure and the
physician group is a physician-only organization; and integrated group practice,
in which the physician group encompasses both the physician practice and the
administrative infrastructure. The choice of equity structure and how it should
be implemented hinge on several legal issues, including the existence of a
corporate-practice-of-medicine statute in the IDS's state, compliance with the
Federal antikickback statute and Stark laws, and various issues regarding the
IDS's tax-exempt status. IDSs also should consider pragmatic issues, particularly
those associated with aligning the economic incentives of the two partners.
PMID- 10182741
TI - Determining when integrated delivery systems should belong to GPOs.
AB - Membership in national group purchasing organizations (GPOs) is a proven way for
healthcare organizations to access supply price discounts through collectively
negotiated contracts. Yet, for various reasons, both suppliers and healthcare
materials managers have expressed dissatisfaction with GPOs. Integrated delivery
systems (IDSs), in particular, may find that negotiating with suppliers
independently is a more cost-effective alternative. Whether an IDS should
participate in group purchasing or negotiate with suppliers on its own depends on
the following factors: whether the IDS would find it relatively simple to get its
clinicians to standardize on certain key supplies; whether the IDS has sufficient
staff to devote to contracting; whether the benefits offered by the GPO do not
outweight the costs of membership; and whether all of the supplier products and
services the GPO makes available also are available through second-tier suppliers
eager to negotiate directly with the IDS.
PMID- 10182742
TI - Rural referrals represent significant revenue for managed care organizations.
AB - A study was conducted to evaluate the potential economic effect of referrals on
managed care organizations by rural physicians to providers outside a rural
county. Patient referral records and associated financial data were gathered for
a three-month period. Referrals by this group of rural primary care physicians to
specialists outside their rural county resulted in an average of approximately
$1,100 of collected revenues per episode of care and in an average of more than
$2,600 of expected payments per hospital inpatient stay. The results from this
study can serve as a preliminary guide for managed care providers as they
structure their services for rural settings.
PMID- 10182743
TI - Hospitalists: an efficient, new breed of inpatient caregivers.
AB - Hospitalists are a relatively new segment of the physician population (primarily
internists and critical care practitioners) specializing in managing the overall
care of hospitalized patients, a responsibility traditionally assumed by primary
care physicians. Managed care organizations, large medical groups, practice
management companies, and hospitals that have adopted inpatient programs
incorporating hospitalists report reductions in length of patient stays,
decreased costs, and improved efficiency of delivery, with no adverse effect on
patient satisfaction. Use of hospitalists is being encouraged by some managed
care organizations, but local medical communities remain largely resistant to the
introduction of hospitalist programs. Healthcare systems should proactively
evaluate the benefits of instituting a hospitalist program.
PMID- 10182744
TI - Avoiding the known prior acts exclusion when insuring newly acquired entities.
AB - Adding a new entity to an organization's existing insurance program can be
problematic if the existing policy contains a known prior acts exclusion clause.
By purportedly excluding claims that a policyholder "could have reasonably
foreseen or discovered," the known prior acts exclusion allows the insurer to
reject those claims after a lawsuit has been filed policyholders should have
known prior acts exclusion clauses removed from their policies or work with their
insurers on language that will clarify the policy regarding this exclusion.
PMID- 10182745
TI - Economic sizing can reduce labor costs.
AB - Fluctuations in census increase staffing costs for most hospitals. By aggregating
patients care units and implementing optimal patient placement rules, a hospital
can reduce its census variation and nursing labor costs for the aggregated units.
There rules are developed through a decision-support technique called economic
sizing to lower overall nursing labor costs. Economic sizing established the
sequence and census levels by which patients are placed on nursing units.
PMID- 10182746
TI - Process improvement program evolves into compliance program at an integrated
delivery system.
AB - An integrated delivery system discovered questionable practices when it undertook
a process-improvement initiative for its revenue-to-cash cycle. These discoveries
served as a wake-up call to the organization that it needed to develop a
comprehensive corporate compliance program. The organization engaged legal
counsel to help it establish such a program. A corporate compliance officer was
hired, and a compliance committee was set up. They worked with counsel to develop
the structure and substance of the program and establish a corporate code of
conduct that became a part of the organization's policies and procedures. Teams
were formed in various areas of the organization to review compliance-related
activities and suggest improvements. Clinical and nonclinical staff attended
mandatory educational sessions about the program. By approaching compliance
systematically, the organization has put itself in an excellent position to avoid
fraudulent and abusive activities- and the government scrutiny they invite.
PMID- 10182747
TI - Group practices need to ensure year 2000 compliance of their electronic systems.
AB - In a group practice, the year 2000 date problem can affect accounting, payment,
and billing systems, as well as medical equipment. With the turn of the century
drawing closer, group practices should ensure that all the electronic systems
that affect their businesses will be year 2000 compliant. Group practices should
develop a plan to address all of the possible year 2000 issues that can affect
their electronic systems. A three-step procedure that will help group practices
implement such a plan comprises creating an inventory of all systems that could
be affected, investigating each system's compliance, and getting written
assurance of year 2000 compliance from all relevant third parties.
PMID- 10182748
TI - Principles and practices board. Issue Analysis 98-1. Compliance with laws and
regulations for healthcare organizations. Healthcare Financial Management
Association.
AB - This is the third Issue Analysis of HFMA's Principles and Practices (P&P) Board.
The P&P Board writes an Issue Analysis in response to the need for practical
information on emerging issues in healthcare financial management. An Issue
Analysis is factual but not authoritative. It is not sent out for public comment
and provides the healthcare industry short-term assistance on emerging issues.
The purpose of P&P Board Issue Analysis 98-1, Compliance with Laws and
Regulations for Healthcare Organizations, is to help healthcare financial
managers understand their responsibility to implement and maintain an effective
internal control system to ensure compliance with laws and regulations.
PMID- 10182749
TI - Collections grow with EDI.
PMID- 10182750
TI - U.S. Supreme Court to address availability of review for reopening denials.
PMID- 10182752
TI - Data trends. Measuring an organization's financial strength.
PMID- 10182751
TI - Hospital, clinic CFOs make transition to managed care well.
PMID- 10182753
TI - Joint Commission's sentinel event policy: disclose or ignore?
PMID- 10182754
TI - NJ hospital group, others advise caution.
PMID- 10182755
TI - Don't report, advise legal counsels nationwide.
PMID- 10182756
TI - Here's what JCAHO says hospitals should report.
PMID- 10182757
TI - Ignore regs at your peril--JCAHO's interested, too.
PMID- 10182758
TI - Should you consider a bloodless program?
PMID- 10182759
TI - Numbers of bloodless facilities swell.
PMID- 10182760
TI - Just how feasible is bloodless surgery?
PMID- 10182761
TI - Hospital administrators: are you Y2K savvy?
PMID- 10182762
TI - ANA Magnet Program promotes excellence.
PMID- 10182763
TI - Don't overlook abstractor training.
PMID- 10182764
TI - Fayette focuses on families, flexibility.
PMID- 10182765
TI - The big hurt. Changing at-risk behaviors can put a big dent in injury rates.
PMID- 10182766
TI - Here's how to prevent laser fires in the OR.
PMID- 10182767
TI - Play it safer. Join OSHA's Voluntary Protection Program.
PMID- 10182768
TI - Codes blues. Feeling down trying to keep up with safety rules? Relief is here.
PMID- 10182769
TI - Label fables: EPA cites hype in 'bugproof' products.
PMID- 10182770
TI - JEMS' 1997 Provider Income Survey.
AB - Each year the JEMS salary survey presents the organizational perspective of
salaries, benefits and working conditions in EMS. In 1997, JEMS editors wanted to
know whether an individual provider's financial perspective changed meaningfully
when their non-EMS income was also considered. That question led to the provider
income survey, which accompanied last November's feature on salaries. For a
review of the most interesting trends and tidbits on EMS provider income, read
on.
PMID- 10182771
TI - A national lesson plan. So what does the National Standard Curriculum mean for
you?
PMID- 10182772
TI - CPAP. A supportive adjunct for congestive heart failure in the prehospital
setting.
PMID- 10182773
TI - Joint Commission on Accreditation of Healthcare Organizations. Improving
Organization Performance chapter.
PMID- 10182774
TI - Texas Health Quality Alliance evaluates health plans.
PMID- 10182775
TI - Most challenging home care standards: tips for better compliance.
PMID- 10182776
TI - Malpractice danger zones. Why primary care is more vulnerable than ever.
PMID- 10182778
TI - Salaries for physician managers are rising with the demand.
PMID- 10182777
TI - Our neighbors don't call 911--they call us.
PMID- 10182779
TI - One mo' time: HCFA tries to figure your practice costs.
PMID- 10182780
TI - How financially secure are young doctors?
PMID- 10182781
TI - When a group's expansion divides a town.
PMID- 10182782
TI - Now hospitals want to be your partner, not your boss.
PMID- 10182783
TI - Who will pay up? FPA's Chapter 11 filing raises doc compensation issue.
PMID- 10182785
TI - Discount settlements. Blues plans pay up to end suits over provider deals.
PMID- 10182784
TI - Shrinking AHA still pays. Executive compensation grows, revenues decline.
PMID- 10182786
TI - Phoenix's new frontier. Western suburbs are targeted for rapid growth.
PMID- 10182787
TI - JCAHO revenues, pay rise.
PMID- 10182788
TI - Bills on parade. Everyone wants to change home health payment system.
PMID- 10182789
TI - Louisville revs up its research engine.
AB - It takes big bucks to attract the best brains in medical research. In Louisville,
Ky., healthcare and political leaders are working together to lure research
dollars. They include, from left, Alliant Health System CEO Stephen Williams,
Louisville Mayor Jerry Abramson, Jewish Hospital HealthCare Services CEO Henry
Wagner, Greater Louisville Inc. CEO Douglas Cobb and Kentucky Gov. Paul Patton.
PMID- 10182790
TI - Ready for growth spurt. For group purchasing, Internet age is still in its
infancy.
PMID- 10182791
TI - Going to market. Preparation helps small hospitals land high ratings as they tap
capital markets.
PMID- 10182792
TI - Blood battle. Hospitals must decide whether to buy safer, but more costly plasma
products.
PMID- 10182794
TI - Hospital gets top billing. Not-for-profit serving entertainment industry has hit
in L.A., may open elsewhere.
PMID- 10182795
TI - Silent or nonexistent? PPOs seen as getting illicit discounts are targeted by
bill.
PMID- 10182793
TI - The forum is with them. AHA sees new unit as a way out of declining revenues.
AB - By gobbling up the San Francisco-based Healthcare Forum, the American Hospital
Association is increasing its stake in the healthcare publishing and management
education business. When the new for-profit company--called the Health InfoSource
-is created Sept. 1, Kathryn Johnson will be at the helm as its founding
president and CEO.
PMID- 10182796
TI - Decapitating healthcare. There's only one way to fix capitation: scrap it and try
something new.
PMID- 10182797
TI - A different view of outsourcing. Survey shows providers want quality and
consolidation, not cost-cutting.
PMID- 10182798
TI - The people strike back. Hospitals' mergers, closures spawn cadres of local
activists.
PMID- 10182799
TI - Big bucks for Y2K.
PMID- 10182800
TI - Private placements. Organizations plug gaps in federal research funding.
PMID- 10182801
TI - Staying home. Interim HealthCare fights industry tides with aggressive
advertising campaign.
PMID- 10182802
TI - The hospitalist.
PMID- 10182803
TI - For nurses, a barrier broken.
PMID- 10182804
TI - Does the scalpel make you quake?
PMID- 10182805
TI - In search of the best: the rankings explained. Here's how we sifted through 6,400
hospitals.
PMID- 10182806
TI - Characteristics of hospice care discharges: United States, 1993-94.
AB - OBJECTIVE: This report presents data on hospice care discharges. Numbers and
percents of discharges are shown by selected characteristics of the agencies from
which the patients were discharged, by selected patient characteristics, by
services provided, by types of personnel that provided the services, and by
diagnoses of these discharged patients. METHODS: The data used for this report
are from the National Center for Health Statistics' 1994 National Home and
Hospice Care Survey. This is an annual survey through which data are collected on
the use of hospices and home health care agencies in the United States. RESULTS:
There were an estimated 328,000 discharges from hospice care from 1,300 hospices
and home health agencies in 1993-94. Death was the reason for discharge for 88
percent of the discharges. Fifty-two percent of the discharges were for men, 73
percent were for patients 65 years of age and over, 79 percent were white, 49
percent were married, and 30 percent were widowed. Eighty-three percent of the
discharged patients were living in a private or semiprivate residence during
their care and 95 percent had a primary caregiver. During the last time service
was provided prior to discharge, 67 percent received help from the agency with at
least one activity of daily living (ADL), 53 percent with at least one
instrumental activity of daily living (IADL), and 30 percent with walking. These
discharges had an average of 2.2 diagnoses at admission; 69 percent had a primary
diagnosis of a malignant neoplasm; and 8 percent had a primary diagnosis of heart
disease.
PMID- 10182807
TI - Smoking behavior of recent mothers, 18-44 years of age, before and after
pregnancy: United States, 1990.
AB - OBJECTIVE: This report presents a comprehensive review of data on the smoking
behaviors of women with a recent birth from the 1990 National Health Interview
Survey. Data on current and lifetime smoking status and smoking behaviors before
and after learning of pregnancy are presented. Selected demographic
characteristics of women--including age, race, education, and family income--are
also presented. METHODS: Data presented in this report are from the 1990 National
Health Interview Survey on Health Promotion and Disease Prevention (NHIS-HPDP).
Questions on pregnancy and smoking were administered as part of this supplement
to women 18-44 years of age who either had a live birth in the 5 years preceding
the interview, or who were pregnant at the time of the interview. These analyses
were limited to women with a live birth in the 5 years preceding the 1990 NHIS
who were not currently pregnant. RESULTS: Of 13,674,000 women with a recent live
birth, about 39 percent had ever smoked, 25 percent smoked in the year before
they became pregnant, and 15 percent smoked during their most recent pregnancy.
Women who smoked prior to learning of their pregnancy were most likely to be
moderate smokers, white women, never married, and of lower income. Women who
smoked after learning of their pregnancy were most likely to be light smokers,
representing a shift in smoking behaviors after learning of pregnancy. Nearly 23
percent of women reported that they stopped smoking altogether after learning of
their pregnancy. CONCLUSIONS: These findings are consistent with data from other
sources and provide support for recently observed trends in smoking and
pregnancy. A majority of women who had ever smoked continued to smoke throughout
pregnancy. Although many women altered their smoking behaviors, only about one
quarter of women reported that they stopped smoking entirely. Public health
service messages must continue to encourage women to stop smoking entirely during
pregnancy to maximize the health benefits to their infants.
PMID- 10182808
TI - Characteristics of elderly nursing home residents: data from the 1995 National
Nursing Home Survey.
AB - OBJECTIVE: This report presents the sociodemographic characteristics, functional
dependencies in the activities of daily living (ADL) and instrumental activities
of daily living (IADL), dental status, primary admission diagnosis, types of
services used, and source of payment of elderly nursing home residents. METHODS:
The data used for this report are from the National Center for Health Statistics'
1995 National Nursing Home Survey's (NNHS) sample of current residents age 65
years and above. The 1995 NNHS is the fourth annual survey of nursing homes. The
first survey was conducted from August 1973 through April 1974, the second was
conducted from May through December 1977, and the third was conducted from August
1985 through January 1986. The 1995 NNHS was conducted from July 1995 through
December 1995. RESULTS: The overall results of the survey indicate that elderly
nursing home residents were predominantly women, 75 years old and over, white,
non-Hispanic, and widowed. A large portion of residents needed assistance in
their ADL's and IADL's. A shifting of the primary source of payment to Medicaid
occurred among residents who used Medicare as their source of payment at the time
of admission.
PMID- 10182809
TI - Medication therapy in ambulatory medical care. National Ambulatory Medical Care
Survey and National Hospital Ambulatory Medical Care Survey, 1992.
AB - OBJECTIVES: This report describes medications provided or prescribed during
ambulatory medical care visits in 1992. Total ambulatory care medication therapy
combines data from office-based physicians, hospital outpatient departments
(OPD's), and hospital emergency departments (ED's). Drug therapy is described
along three dimensions: number of drugs provided or prescribed (drug mention),
whether a visit had any drugs mentioned (drug visit), and average number of drugs
mentioned per 100 visits (drug mention rate). Utilization in ambulatory care
settings is compared in terms of patient, drug, provider, and visit
characteristics. METHODS: Annual use of medication therapy was determined using
data collected in the 1992 National Ambulatory Medical Care Survey (NAMCS) and
the National Hospital Ambulatory Medical Care Survey (NHAMCS). NAMCS includes
office visits to nonfederal physicians principally engaged in office practice.
The target universe of NHAMCS includes visits to ED's and OPD's of non-Federal,
short-stay, or general hospitals. Sample data were weighted to produce annual
estimates. Drug mentions are defined as the number of drugs mentioned on the
patient record from. RESULTS: An estimated 1.1 billion medications were provided
or prescribed at ambulatory care visits in 1992. The setting with the greatest
percent of visits with medication therapy was the ED; OPD's had the lowest
percent with medications. Patients at the ED were provided more pain relief type
drugs. The rate of drug mentions and percent of visits with medications were
significantly higher in OPD clinics of general medicine and pediatrics compared
with other types of OPD clinics. In office-based settings, physicians
specializing in cardiovascular diseases were most likely to prescribe
medications. Also, cardiovascular-renal type drugs accounted for the largest
percent of office-based drug mentions. Visits with illness diagnoses are most
likely to receive medication therapy. Trend data comparing 1980 to 1992 office
based mentions showed significant changes on several characteristics: single
ingredient drug status, physician specialty, and patient age. CONCLUSIONS: The
profile of patients using office- and hospital-based ambulatory care settings are
quite different as is the case-mix of conditions. These differences play an
important role in medications utilized. The aging of the U.S. population from
1980 to 1992 appeared to have significant effects on several drug mention
characteristics.
PMID- 10182810
TI - 1995 summary: National Hospital Discharge Survey.
AB - OBJECTIVES: This report presents national estimates of the use of non-Federal
short-stay hospitals in the United States during 1995. Numbers and rates of
discharges, diagnoses, and procedures are shown by age and sex. Discharges are
also shown by geographic region of hospital. Average lengths of stay are
presented for discharges and selected diagnostic categories. METHODS: The
estimates are based on medical abstract data collected through the National
Hospital Discharge Survey for 1995. The survey has been conducted annually by the
National Center for Health Statistics since 1965. Diagnoses and procedures
presented are coded according to the International Classification of Diseases,
9th Revision, Clinical Modification, or ICD-9-CM.
PMID- 10182812
TI - Applying QI principles to personal life.
PMID- 10182811
TI - Trends and differential use of assistive technology devices: United States, 1994.
AB - OBJECTIVE: This report presents data on annual estimates of the prevalence of use
of selected assistive technology devices for vision, hearing, mobility, and
orthopedic impairments, including missing limbs. Also presented are statistics on
trends in the prevalence of use of selected mobility assistive technology devices
for the years 1980, 1990, and 1994. METHODS: The data used for this report are
from the 1994 National Health Interview Survey on Disability (NHIS-D), Phase I,
which was co-sponsored by a consortium of U.S. Federal agencies and private
foundations. All estimates are based on data from the NHIS-D, Phase I, which
represent the civilian, noninstitutional population of the United States.
RESULTS: An estimated 7.4 million persons in the U.S. household population used
assistive technology devices for mobility impairments, 4.6 million for orthopedic
impairments (including missing limbs), 4.5 million for hearing impairments (not
including impairments fully compensated by hearing aids), and 0.5 million for
vision impairments. Use of any mobility device for all ages had the highest
prevalence rate at 28.5 per 1,000 persons. There was a positive correlation
between an increase in age and the increase in the prevalence rate of device
usage; for example, of persons in the age group 65 years and over, the rate of
mobility, hearing, and vision device usage was more than 4 times the rate for the
total population. CONCLUSION: Assistive technology use has increased because of
population size, age composition changes, and a change in the rate of use.
Medical and technological advances along with public policy initiatives have also
contributed to increased usage.
PMID- 10182813
TI - Are you managing your stress?
PMID- 10182814
TI - 'High touch' approach lowers C-section rates.
PMID- 10182816
TI - Personal renewal for professional growth.
AB - When healthcare professionals burn out, they put themselves and their
organizations at risk. The solution, career specialists say, begins with looking
closely at conflicts between personal and professional values. Ultimately it
might lead to further education, a career change or finding a way to spend more
time in one's area of expertise.
PMID- 10182815
TI - Hospital policy fights resistant bacteria.
PMID- 10182817
TI - Patient-driven indicators for quality.
AB - Measuring quality encompasses many factors, including patients' perceptions of
providers' performance. The Joint Commission on Accreditation of Healthcare
Organizations now includes questions developed by The Picker Institute in its
ORYX initiative as a way of gauging how well providers meet patients' needs for
education, self-care and expectations for treatment.
PMID- 10182818
TI - Researchers call for more, better data on women's health issues.
PMID- 10182819
TI - A new resource: empowered patients.
AB - Patients who have access to healthcare information on the Internet or elsewhere
or who have learned to demand interaction with their providers can be
intimidating--and also one of a provider's biggest assets. When providers take
the time to talk with patients about their conditions, to involve them in
decisionmaking and to give them access to information, patients can become active
participants in the care process. That shift in roles can reduce inappropriate
utilization, cut costs and increase satisfaction.
PMID- 10182820
TI - New attitudes shape the struggle to lose weight.
PMID- 10182821
TI - The benefits of modest weight loss.
PMID- 10182822
TI - Weight and work.
PMID- 10182823
TI - Work-site review: peer support pays off.
PMID- 10182824
TI - Data watch. The impact of obesity on health and health care costs.
PMID- 10182825
TI - The medical puzzle of obesity.
PMID- 10182826
TI - The dynamics of power in the marketplace.
PMID- 10182827
TI - FPA struggles cast pall over future of PPMs.
PMID- 10182828
TI - Do integrated healthcare strategies enhance quality?
PMID- 10182829
TI - Obstetric and gynecologic devices; reclassification and classification of medical
devices used for in vitro fertilization and related assisted reproduction
procedures--FDA. Final rule.
AB - The Food and Drug Administration (FDA) is announcing that it is reclassifying
instrumentation intended for use in in vitro fertilization (IVF) and related
assisted reproduction technology (ART) procedures, including but not limited to
gamete intrafallopian transfer (GIFT), embryo transfer (ET), and intracytoplasmic
sperm injection (ICSI), from class III (premarket approval) to class II (special
controls). FDA is also reclassifying assisted reproduction microscopes and
microscope accessories from class III to class I. This reclassification is on the
Secretary of the Department of Health and Human Services' (the Secretary's) own
initiative based on new information. Accordingly, the order is being codified in
the Code of Federal Regulations. Upon the effective date, this Federal Register
document may be cited in the absence of an existing predicate device which would
be used to support substantial equivalence. Elsewhere in this issue of the
Federal Register, FDA is announcing the availability of a draft guidance entitled
"Devices Used for In Vitro Fertilization and Related Assisted Reproduction
Procedures: Submission Guidance for a 510(k)."
PMID- 10182830
TI - Civilian Health and Medical Program of the Uniformed Services (CHAMPUS); TRICARE
Program; reimbursement--DoD. Final rule.
AB - This final rule revises certain requirements and procedures for reimbursement
under the CHAMPUS program, the purpose of which is to implement a comprehensive
managed health care delivery system composed of military medical treatment
facilities and CHAMPUS. Issues addressed in this rule include: implementation of
changes made to the Medicare Prospective Payment System (PPS) upon which the
CHAMPUS DRG-based payment system is modeled and required by law to follow
wherever practicable, along with changes to make our DRG-based payment system
operate better; clarification of payment reduction for noncompliance with
required utilization of publication of list of ambulatory surgery procedures;
limitation on ambulatory surgery group payment rates; extension of the balance
billing limitations currently in place for individual and professional providers
to non-institutional, non-professional providers; adjustment of the CHAMPUS
maximum allowable charge (CMAC) rate in the small number of cases where the CMAC
rate is less than the Medicare rate; implementation of the government-wide
debarment rule where any provider excluded or suspended from CHAMPUS shall be
excluded from all other programs and activities involving Federal financial
assistance, such as Medicare or Medicaid; elimination of the requirement for non
participating providers to file claims; and revision of the ambulatory surgery
cost-share information to enable the cost-share to be assessed against the
facility claim instead of the primary surgeon's claim.
PMID- 10182831
TI - Release of information from Department of Veterans Affairs records--VA. Proposed
rule.
AB - This document proposes to amend Department of Veterans Affairs (VA) regulations
governing the confidentiality and release of VA records subject to the Privacy
Act, the Freedom of Information Act (FOIA) (including the Electronic Freedom of
Information Act Amendments of 1996), and the veterans' records confidentiality
statute. The proposed rule sets forth a mechanism for the public to obtain
information from the VA. The proposed rule is intended to maximize public
availability of VA records to the extent permitted by law and considerations such
a personal privacy or law enforcement. Essentially these provisions consist of
restatements of statute, interpretations of statute, interpretations of case law,
interpretations of Executive Orders, and clarification. The proposed amendments
also would implement the Electronic Freedom of Information Act Amendments of
1996, court decisions and Executive Branch guidance issued since the regulations
were originally published. Further, this document proposes to delegate authority
to the Assistant General Counsel for Professional Staff Group IV for making final
Departmental decisions on appeals under the Freedom of Information Act, the
Privacy Act, and 38 U.S.C. 5701 and 5705. This would simplify decision making by
allowing the highest level individual with direct responsibility for decision
making to issue decisions.
PMID- 10182832
TI - Notice of availability of funds; economic and outcome analysis of antimicrobial
resistance in hospital-acquired infections among intensive care unit patients-
CDC.
PMID- 10182833
TI - A kinder, gentler EPA.
PMID- 10182834
TI - Beyond good intentions: accountability for community benefits.
PMID- 10182836
TI - The mission is the message.
PMID- 10182835
TI - Getting the goods ... collecting community benefits data.
PMID- 10182837
TI - Results outside the walls.
PMID- 10182838
TI - Mergers--true integrations.
AB - This article is the second of a two part series on clinical consolidation in
mergers. Part 1 addressed typical consolidations that occur in mergers and why
clinical consolidation is so often overlooked. It discussed the quality and
efficiencies improvements that can occur if clinical consolidation is carried out
successfully. Part 2 details the steps of the clinical consolidation process
that, if undertaken early and involving physicians and staff, will lead to a
successful outcome.
PMID- 10182839
TI - Keys to organ donation: a supportive staff and a great recovery connection.
PMID- 10182840
TI - A return to productivity.
PMID- 10182841
TI - Hospital joint ventures. IRS focuses on who is in control.
AB - Revenue Ruling 98-15 provides insight into how the IRS will examine complex
financial and operational relationships between taxable and tax-exempt
organizations. It identifies certain critical factors that may affect outcomes in
any given case such as the ability of the nonprofit partner to control the
charitable purpose of the entity.
PMID- 10182842
TI - A plague on both your houses. Health care ignores public opinion at its own
peril.
PMID- 10182843
TI - Mechanical or healing art?
PMID- 10182845
TI - The hospitality in hospital.
PMID- 10182844
TI - It's all about relationships.
PMID- 10182846
TI - Making a better place to live.
PMID- 10182847
TI - The 85/15 formula.
PMID- 10182848
TI - At-will employment status.
PMID- 10182849
TI - Starting with seniors. Building a model for care across the continuum.
PMID- 10182850
TI - How to hire a money manager.
PMID- 10182851
TI - Conference calling: new twists to a business staple.
PMID- 10182852
TI - How we build healthy communities.
PMID- 10182853
TI - Building healthy communities.
PMID- 10182854
TI - Complementary care: expanding patients' options.
PMID- 10182855
TI - St. Vincent de Paul Senior Services: meeting the needs of Chicago's elderly.
PMID- 10182856
TI - HCFA publishes final rules for reimbursing clinical social work under Medicare
Part B.
PMID- 10182857
TI - Work redesign reduces home health care visits.
PMID- 10182858
TI - Specialized health care facilities of the future are competing in the niches.
PMID- 10182859
TI - Hospital bed demand: calculating need for facilities in the millennium.
PMID- 10182860
TI - Celebration Health: a "millennium model" of the hospital of the future.
PMID- 10182861
TI - Facilities of the future: new models of care, innovative services, and
alternative settings.
PMID- 10182862
TI - The carrot and the stick: how to make sure your documentation's correct.
AB - With federal fraud investigators labeling discharge planning a risk area in their
model compliance plans, case managers are finding themselves on the front lines
of the corporate compliance wars. Experts warn that how well you document your
work could affect your hospital's accreditation and ability to participate in
Medicare. When poor documentation exists in the discharge planning process, it's
probably because case managers didn't receive adequate training in discharge
planning, experts say. Poor documentation also can result from lax oversight on
the part of supervisors. To prevent documentation errors in discharge planning,
case managers can become compliance officers for their departments. After all,
experts say, compliance is just another form of quality improvement.
PMID- 10182863
TI - Association releases new pediatric discharge guides.
AB - An expert panel convened by the American Academy of Pediatrics (AAP) in Elk Grove
Village, IL, says traditional guidelines for the discharge of high-risk newborns
are inadequate because they can't be tailored easily to many individual cases. In
its own just-released guidelines, the AAP distinguishes among four categories of
high-risk newborns, including preterm infants, infants who require technological
support, those at risk because of family issues, and those whose irreversible
condition may result in early death. According to the guidelines, any effective
discharge plan for high-risk infants should include the following six steps:
Parental education, implementation of primary care, evaluation of unresolved
medical problems, development of the home care plan, identification and
mobilization of surveillance and support services, and determination and
designation of follow-up care.
PMID- 10182864
TI - CM program helps make hospital profitable.
AB - By implementing a case management program for the first time last year, Bradford
Regional Medical Center (PA) managed to turn around a trend in which the 150-bed
hospital lost $2.6 million in operating expenses in 1997. Case managers were
assigned not to units but to groups of physicians to gain physician trust before
focusing on resource utilization. Since the department was formed, the
hospitalwide length of stay has dropped by half a day. The next step in the
development of the program is to extend it beyond acute care into physicians'
offices and into Bradford's nursing home to reduce rehospitalization,
particularly for congestive heart failure patients.
PMID- 10182865
TI - Perioperative pathways for ambulatory surgery.
PMID- 10182866
TI - Hospital goes on-line with electronic medical record.
AB - In May, Texas Children's Hospital in Houston went live with a pilot project to
test the use of electronic medical records at the facility. Currently, the system
is available for use by clinicians in selected units who have access to results
data. In the hospital's cancer center, a related pilot program has physicians and
nurse practitioners entering their clinical notes and order sets electronically,
cutting out the need for transcription. Project leaders emphasize that achieving
physician buy-in has been crucial to the success of the project, especially as
electronic notes and order sets become standard throughout the hospital.
PMID- 10182867
TI - Here's how CHF education saved $173,000 for hospital.
PMID- 10182868
TI - UCLA rewrites the script for academic networks.
AB - Known worldwide for its high-tech tertiary and quaternary specialties, UCLA
Medical Center developed a two-pronged strategy for maintaining referral volume
in the face of intensifying managed care cost/referral control. Its 1. Recruited
primary care clinician educators, and built a network of affiliated PC physicians
and small PC offices in its historical service area. Now it draws 36% of
outpatient visits, 40% of fee-for-service Medicare discharges, and 20% of total
discharges from its network, providing "role models for academic-affiliated
primary care medicine." 2. Began to bolster its draw further afield, developing
long-distance consultation relationships/shared protocols with specialists in the
rest of the L.A. Basin (home to another 45% of UCLA's business), and as far away
as Las Vegas.
PMID- 10182869
TI - Will pharmacy costs overwhelm medical networks?
AB - A crisis looms as medical networks, already reeling from ongoing drug cost
increases, face the Viagra crisis and anticipate the release of whole groups of
expensive new therapeutics on the market.
PMID- 10182870
TI - Practice parameters. The most recent Deloitte & Touche survey confirms the bad
news about direct MD practice acquisition.
PMID- 10182871
TI - Trade groups seek nontherapy ancillary pass-through under PPS.
PMID- 10182872
TI - Industry angry over OIG recommendation that PPS rates be cut.
PMID- 10182873
TI - MDS (minimum data set) completion, locking and transmission requirements.
PMID- 10182874
TI - How to make corrections to a locked MDS (minimum data set).
PMID- 10182875
TI - Maximizing AIDS expertise.
AB - Breakthroughs in treatments for HIV/AIDS are offering new hope. Health plans are
identifying the right professionals to coordinate these promising but complex new
treatments.
PMID- 10182876
TI - Managed care and the tobacco wars.
PMID- 10182877
TI - Healthy Maine 2000.
PMID- 10182878
TI - Are you ready for the year 2000?
AB - The new millennium will bring information systems challenges that have broad
implications for health plans. Experts offer advice for assessing and preparing
core information systems.
PMID- 10182879
TI - A personal touch. When it comes to serving Medicare members, a high-touch
approach pays off.
PMID- 10182880
TI - On the road to a lifetime of good health. Using mobile vans, health plans are
offering the communities they serve access to coordinated health care.
PMID- 10182881
TI - Connecting with consumer groups.
PMID- 10182882
TI - A partnership to improve minority health.
PMID- 10182883
TI - The pain management puzzle.
PMID- 10182884
TI - By the numbers. Consumer satisfaction with health plans.
PMID- 10182885
TI - The impact of reimbursement changes for intracoronary stents on providers and
Medicare.
AB - CONTEXT: New Medicare reimbursement policies will move stents into a different
diagnosis-related group (DRG) than conventional balloon angioplasty (percutaneous
transluminal coronary angioplasty [PTCA]). OBJECTIVE: To examine the financial
impact on hospitals and Medicare of these planned changes, taking into account
costs, reimbursement, and the cost-offset effect of prevented complications.
DESIGN: The economic impact of proposed reimbursement changes was modeled by
using a retrospective clinical and economic data set from a single institution.
PATIENTS AND METHODS: A total of 421 consecutive interventional cases from 1996
were examined by using actual cost data. The new, proposed revenues were assigned
to these cases. From the hospitals' perspective, the focus was on contribution
margin (the difference between revenues and costs), risk adjusted for case-mix
severity. From Medicare's perspective, the focus was on expenditures. Various
assumptions were adopted for two clinical variables: the effectiveness of stents
in preventing the major PTCA-related complications of myocardial infarction and
coronary artery bypass graft surgery and the relative proportions of myocardial
infarction and coronary artery bypass graft surgery in the mix of complications.
Under current Medicare DRG policies, coronary artery bypass graft surgery is
highly profitable for hospitals, whereas myocardial infarction as a complication
of PTCA has a negative financial impact. RESULTS: Under the new Medicare
reimbursement policies, hospitals experience higher profitability with stents
than with conventional PTCA under most assumed levels of clinical effectiveness
and mixes of myocardial infarction and coronary artery bypass graft surgery. For
Medicare, under most circumstances (including percentages of stent use and levels
of clinical effectiveness that represent contemporary practice) stents lead to
greater expenditures. CONCLUSIONS: Medicare reimbursement changes will
substantially realign previously misaligned financial and clinical incentives for
hospitals. The immediate effect on hospitals will be to enhance profitability,
whereas the effect on Medicare will be to increase expenditures.
PMID- 10182886
TI - Formulary limitations and the elderly: results from the Managed Care Outcomes
Project.
AB - OBJECTIVE: To examine whether restrictive formularies are associated with
differences in healthcare resource utilization, including number of office
visits, prescriptions, and hospitalizations, and whether this association varies
by age. STUDY DESIGN: Cross-sectional, longitudinal study. PATIENTS AND METHODS:
Patients enrolled in one of six health maintenance organizations in six different
states, three in the eastern and three in the western United States, were
eligible for the study. Data from between 1309 and 3938 patients were available
for analysis for each of the five diseases studied, for a total of 12,997
patients across all study diseases. Healthcare utilization by patients in the
study included more than 99,000 office visits, 1000 hospitalizations, and 240,000
prescriptions. We used severity-adjusted prescription counts, prescription costs,
office visit counts, and measures of inpatient hospital utilization to assess the
effects of formulary limitations. RESULTS: We found positive, significant
associations between the independent variable formulary limitations in drug class
and the dependent variables measuring resource utilization. These associations
were sometimes significantly greater for elderly patients after controlling for
severity of illness and other variables. CONCLUSIONS: Common strategies for
decreasing drug expenditures may be associated with higher severity-adjusted
resource utilization. In specific areas, this association is more pronounced in
the elderly.
PMID- 10182887
TI - The clinical value of commonly used spinal fluid diagnostic studies in the
evaluation of patients with suspected multiple sclerosis.
AB - OBJECTIVE: This study was designed to evaluate the diagnostic value of
cerebrospinal fluid (CSF) oligoclonal banding and immunoglobulin G (IgG)
production in the diagnosis of multiple sclerosis. STUDY DESIGN: Spinal fluid
changes in patients with suspected multiple sclerosis were compared with clinical
data to determine sensitivity, specificity, and predictive value of the
procedures. The results were evaluated in terms of cost compared with clinical
utility in the managed care environment. PATIENTS AND METHODS: The CSF
oligoclonal banding and CSF IgG index were measured in 50 patients being
evaluated for possible multiple sclerosis at a multispecialty group practice
clinic. RESULTS: CSF oligoclonal banding had a sensitivity of 75% and a
specificity of 92% in the diagnosis of multiple sclerosis. The CSF IgG index had
a sensitivity of 75% and a specificity of 95% in the diagnosis of multiple
sclerosis. CONCLUSIONS: Although neither test would identify 100% of patients
with multiple sclerosis, the combination of CSF oligoclonal banding and an
elevated CSF IgG index correctly identified most patients with multiple sclerosis
and excluded all patients without the disease in this patient population.
PMID- 10182888
TI - The cost of inpatient endometriosis treatment: an analysis based on the
Healthcare Cost and Utilization Project Nationwide Inpatient Sample.
AB - OBJECTIVE: To determine the prevalence and cost of endometriosis-related
hospitalizations based on the Nationwide Inpatient Sample (NIS) from the
Healthcare Cost and Utilization Project (HCUP-3). STUDY DESIGN: Retrospective
analysis based on nationwide clinical practice data. PATIENTS AND METHODS: Data
were obtained for 1991 and 1992 from the HCUP-NIS database, which was a 20%
sample of all US hospital discharges. ICD-9 codes (236.0, 617.0 to 617.9) were
used to identify females, aged 15 to 54, with endometriosis as a diagnosis. The
distribution of endometriosis admissions by admission type, length of stay (LOS),
mean total charge, specific types of endometriosis, principal procedures, and
other diagnosed diseases was described. RESULTS: In 1991 and 1992, 37,273
(22.6/1000) and 38,834 (23.7/1000) hospital admissions, respectively, were for
endometriosis (as any diagnosis). The average LOS and total hospital charges for
endometriosis as the primary diagnosis were 3.8 days and $6,597 for 1991, and 3.5
days and $7,450 for 1992. Most endometriosis admissions occurred in females aged
35 to 49. About 87% of the endometriosis hospitalizations were routine
admissions. The most common diagnosis was endometriosis of the uterus (51%); the
most common procedure was a total abdominal hysterectomy (55%-60%). Older and
African-American patients had the longest LOS and the highest total charges. The
estimated total hospitalization costs, as represented by hospital charges, for
women with endometriosis as the primary diagnosis in the United States were $504
million for 1991 and $579 million for 1992. CONCLUSION: Endometriosis-related
hospitalization is a major burden on healthcare systems.
PMID- 10182889
TI - Identification and assessment of high-risk seniors. HMO Workgroup on Care
Management.
AB - CONTEXT: Many older adults with chronic illnesses and multidimensional needs are
at high risk of adverse health outcomes, poor quality of life, and heavy use of
health-related services. Modern proactive care of older populations includes
identification of such high-risk individuals, assessment of their health-related
needs, and interventions designed both to meet those needs and to prevent
undesirable outcomes. OBJECTIVE: This paper outlines an approach to the tasks of
identifying and assessing high-risk seniors. Intervention identification of high
risk seniors (also called case finding) is accomplished through a combination of
periodic screening, recognition of high-risk seniors by clinicians, and analysis
of administrative databases. Once identified, potentially high-risk individuals
undergo on initial assessment in eight domains: cognition, medical conditions,
medications, access to care, functional status, social situation, nutrition, and
emotional status. The initial assessment is accomplished in a 30- to 45-minute
interview conducted by a skilled professional--usually one with a background in
nursing. The data are used to link some high-risk persons with appropriate
services and to identify others who require more detailed assessments. Detailed
assessment is often performed by interdisciplinary teams of various compositions
and methods of operation, depending on local circumstances. CONCLUSION: The rapid
growth in Medicare managed care is presenting many opportunities for developing
more effective strategies for the proactive care for older populations.
Identification and assessment of high-risk individuals are important initial
steps in this process, paving the way for testing of interventions designed to
reduce adverse health consequences and to improve the quality of life.
PMID- 10182890
TI - Outpatient antidepressant utilization in a Dutch sick fund.
AB - OBJECTIVE: To identify quality improvement opportunities in the management of
depression by evaluating patterns of antidepressant use and concurrent use of
anxiolytics or sedative/hypnotics among patients who initiated therapy with
amitriptyline, fluoxetine, fluvoxamine, or paroxetine. DESIGN: A longitudinal,
retrospective study using electronic prescription data from a Dutch sick fund,
ZAO Zorgverzekeringen. PATIENTS AND METHODS: The study patients (n = 2,554)
initiated therapy between October 1, 1994 and December 31, 1995. Follow-up
periods were 6 months (antidepressant use) and 60 days (concurrent anxiolytic and
sedative/hypnotic use). RESULTS: The three key findings were as follows: (1) the
majority of patients received less than 4 months of therapy (more common for
patients receiving amitriptyline); (2) the average daily doses for initial
prescriptions for all four study drugs were below the recommended therapeutic
minimums for depression (overall and final amitriptyline doses also were
consistently low); and (3) the incidence of concurrent anxiolytic and
sedative/hypnotic use during days 2-60 after antidepressant therapy initiation
was 18.2%. CONCLUSION: The study suggests that patients in this Dutch sick fund
were not likely to receive either adequate antidepressant doses or adequate
durations of therapy relative to Dutch guidelines for the treatment of
depression. These findings are consistent with findings in other Dutch, European,
and US studies and may present opportunities for quality improvement.
PMID- 10182891
TI - Inborn errors of metabolism: medical and administrative "orphans".
AB - CONTEXT: Inborn errors of metabolism are genetic conditions that affect the
normal biochemical functions of the body in any organ and at any age. More than
500 metabolic diseases are known; almost all are classified as orphan diseases
under the US Food and Drug Administration guidelines (incidence < 200,000
persons) and each has its own requirements for diagnosis and treatment.
Management of these complex, lifelong, multisystem disorders often requires a
coordinated, multidisciplinary approach involving several subspecialists and
which may include complex laboratory evaluations, genetic counseling, nutritional
therapy, and unusual therapeutic approaches that have been used in only a small
number of cases. RESULTS: Not infrequently, inborn errors of metabolism fall
outside current standard diagnostic and treatment guidelines of managed care
plans. This results in delays in diagnosis and appropriate management, with
increased costs to patients and to society. CONCLUSIONS: Patients with inborn
errors of metabolism should not be discriminated against and all health plans
should specify that access to specialists and metabolic centers are a covered
benefit of the plan. The acceptance of treatment guidelines, the development of
international disease classification codes for the disorders, and the performance
of cost-benefit analyses would all greatly facilitate this process. However,
without recognition that these disorders require such services, and steps to
provide them by the insurance industry, the care of children with metabolic
disorders and other chronic diseases will continue to be a source of frustration
and anger among the caregivers and the families they serve.
PMID- 10182892
TI - Generic drug product equivalence: current status.
AB - This activity is designed for healthcare professionals involved in the selection
of multisource drug products. GOAL: To understand the basis for approval of
generic drug products by the Food and Drug Administration. OBJECTIVES: 1.
Identify the criteria employed by the Food and Drug Administration to approve
generic drug products. 2. Discuss controversial issues that have been raised
relative to generic drug products. 3. Identify narrow therapeutic index drugs. 4.
Describe the different types of bioequivalence studies that are required by the
Food and Drug Administration. 5. Discuss the responsibilities underlying the
selection of multisource drug products by healthcare professionals.
PMID- 10182893
TI - Toomey sets sight on health data, partnerships.
PMID- 10182894
TI - Federalizing protection of health information: HHS proposes privacy legislation.
PMID- 10182895
TI - GHA/DHR partnership: new goals set for Georgia's cancer registry.
PMID- 10182896
TI - Nation awakens to the plight of rural hospitals.
PMID- 10182897
TI - Federal government takes aim at U.S. hospitals.
PMID- 10182898
TI - Ohio court dismisses lab unbundling challenge, suggests HHS may be heavy-handed.
PMID- 10182899
TI - An association that reflects its members.
PMID- 10182901
TI - 1998 GHA legislative agenda.
PMID- 10182900
TI - Denial of tax-exempt status demonstrates IRS position on hospital joint ventures.
PMID- 10182902
TI - Antitrust challenges to hospital mergers back in the news.
PMID- 10182903
TI - Three Georgia congressmen discuss balanced budget, health care issues.
PMID- 10182904
TI - The budget deal.
PMID- 10182905
TI - Potential for provider profits exists under one model.
PMID- 10182906
TI - Six questions to ask when eyeing Medicare pharmacy risk.
AB - Don't be surprised if your Medicare HMO asks you to take risk for pharmacy. As
the cost of the benefit skyrockets, plans are turning to providers who do the
prescribing to better control it. Here's how to determine whether you should take
the risk and some tips on what should be in your contract.
PMID- 10182907
TI - Mississippi Medicaid program targets drug therapy compliance.
AB - Can pharmacists serving as disease management and drug therapy counselors to
patients help reduce Medicaid costs? Program administrators hope so as they
launch a new effort in which pharmacists serve as providers of disease management
services and are paid for having counseling sessions with recipients.
PMID- 10182908
TI - Compliance plan can head off problems with Medicare fraud and abuse laws.
AB - Don't assume that compliance issues are only for your Medicare managed care
organization. Providers who don't understand how HIP AA and the BBA work together
to hold providers and plans accountable for fraud and abuse can set themselves up
for career-ending mistakes, experts warn. Here's how to avoid practices that
could be considered Medicare fraud or abuse.
PMID- 10182909
TI - Survey highlights trends in managing Medicare drug costs.
AB - Data File: Before you assume risk for your Medicare risk plan's pharmacy benefit,
you ought to understand what the benefit is, how it works, and how much it's
likely to cost you. Find out the latest trends and benchmark data in managed
Medicare pharmacy from a recent survey.
PMID- 10182910
TI - Reducing treatment variation is key to managing cancer.
PMID- 10182911
TI - Integrate obesity management strategies with your DM program.
AB - The American Heart Association recently upgraded obesity to be a significant risk
factor for heart disease and federal health officials issued new clinical
guidelines for managing this risk in adults. Find out how one major health plan
has incorporated medical weight management into all of its chronic DM programs.
PMID- 10182912
TI - New weight guidelines equate risk of death and illness to BMI (body mass index).
PMID- 10182913
TI - New study confirms benefit of disease management for less severe cases of
diabetes.
AB - One of the largest providers of diabetes DM has announced results of a project
with seven major HMOs. After one year, costs for hospital and outpatient care are
down and HbA1c testing, eye, foot and cholesterol exams are markedly up. Find out
how these landmark results are likely to impact your diabetes DM efforts.
PMID- 10182914
TI - Non-drug therapies are highly beneficial in Parkinson's disease, but seldom
prescribed.
AB - Nearly 2 million Americans, mostly men, face the agony of Parkinson's Disease in
later years, but few DM programs address the condition. Experts who provide
physical, occupational, speech and nutritional therapy tell why their services
should be utilized for Parkinson's patients in a managed care environment.
PMID- 10182915
TI - Asthma patients get assertive about helping themselves in innovative DM program.
AB - A unique approach to asthma self-management stresses the importance of helping
patients become more aggressive with doctors, friends, and family members whose
habits may exacerbate their symptoms.
PMID- 10182916
TI - Is utilization out of your hands? Try these strategies.
PMID- 10182917
TI - Careful medical management can help avoid 'shock claims'.
AB - By partnering with three specialized medical management firms, a Washington-based
company has developed a novel approach to managing the financial and medical risk
of catastrophic care.
PMID- 10182918
TI - Orthopedics presents new wrinkle in contact capitation.
AB - Data Insight: Contact capitation has burst on the scene like a rocket, but
widespread adoption of the methodology has been hindered by the lack of equitable
methods to distribute payments to physicians. Here's help.
PMID- 10182919
TI - Will your IPA pass this financial checkup?
AB - IPAs often accept capitation without considering whether their infrastructure is
sufficient to manage financial risk. One of the most common blunders is failing
to link their accounting and claims systems, says one CPA.
PMID- 10182920
TI - Use group-based incentives to improve individual performance.
AB - A mixed model medical group in New Jersey gave its physicians the authority to
develop incentives that would encourage collegiality while ensuring access to
care and quality outcomes. Here are their results.
PMID- 10182921
TI - Marketplace. Out of their troubles, PPMs may find what they can truly do better.
PMID- 10182922
TI - Perspectives. Allegheny's collapse triggers a debate over pluses of health care
conglomerates.
PMID- 10182923
TI - Marketplace. Disease management: now the focus is on persuading patients to
comply.
PMID- 10182924
TI - Perspectives. Patient protection: key differences emerge on information, appeals,
access, and scope provisions; but bills languish.
PMID- 10182925
TI - Perspectives. New estimates credit managed care with savings, but upward
pressures loom.
PMID- 10182926
TI - David Gagnon, President, National Perinatal Information Center. Interview by
James A. Johnson.
PMID- 10182927
TI - Achieving effective trusteeship.
PMID- 10182928
TI - Managing behavioral health.
PMID- 10182929
TI - Trust between managers and physicians in community hospitals: the effects of
power over hospital decisions.
AB - Trust is a key element of effective work relationships between managers and
physicians. Despite its importance, little is known about the factors that
promote trust between these two professional groups. We examine whether manager
and physician power over hospital decisions fosters manager-physician trust. We
expect that with more power, managers and physicians will have greater control to
enforce decisions that benefit the interests of both groups. Subsequently, they
may gain confidence that their interests are supported and have more trust for
each other. We test proposed hypotheses with data collected in a national study
of chief executive officers and physician leaders in community hospitals in 1993.
Findings indicate that power of managers and physicians over hospital decisions
is related to manager-physician trust. Consistent with our expectations,
physicians perceive greater trust between the two groups when they hold more
power in four separate decision-making areas. Our hypotheses, however, are only
partially supported in the manager sample. The relationship between power and
trust holds in only one decision area: cost/quality management. Our findings have
important implications for physician integration in hospitals. A direct
implication is that physicians should be given the opportunity to influence
hospital decisions. New initiatives, such as task force committees with open
membership or open forums on hospital management, allow physicians a more
substantial involvement in decisions. Such initiatives will give physicians more
"voice" in hospital decision making, thus creating opportunities for physicians
to express their interests and play a more active role in the pursuit of the
hospital's mission and objectives.
PMID- 10182930
TI - Charitable care and the nonprofit paradigm.
AB - Nonprofit hospitals have begun to focus once again on serving the health needs of
their communities. Governmental needs for additional revenue and for-profit
hospitals' contention that tax exemptions give nonprofit hospitals an unfair
competitive advantage have resulted in changes in laws and regulations and have
caused a change in the role of nonprofit hospitals. As local governments become
more responsive to the health needs of their communities, they are requiring
nonprofit hospitals to become more responsive as well. Laws, regulations, and
court decisions have begun to require nonprofit hospitals to provide charity care
and services at levels equal to the amount of their exempt taxes. In response,
nonprofit hospitals are developing community benefit programs and public health
services.
PMID- 10182931
TI - Emergency department patient satisfaction: customer service training improves
patient satisfaction and ratings of physician and nurse skill.
AB - Customer service initiatives in healthcare have become a popular way of
attempting to improve patient satisfaction. This study investigates the effect of
clinically focused customer service training on patient satisfaction in the
setting of a 62,000-visit emergency department and level I trauma center.
Analysis of patient complaints, patient compliments, and a statistically verified
patient-satisfaction survey indicate that (1) all 14 key quality characteristics
identified in the survey increased dramatically in the study period; (2) patient
complaints decreased by over 70 percent from 2.6 per 1,000 emergency department
(ED) visits to 0.6 per 1,000 ED visits following customer service training; and
(3) patient compliments increased more than 100 percent from 1.1 per 1,000 ED
visits to 2.3 per 1,000 ED visits. The most dramatic improvement in the patient
satisfaction survey came in ratings of skill of the emergency physician,
likelihood of returning, skill of the emergency department nurse, and overall
satisfaction. These results show that clinically focused customer service
training improves patient satisfaction and ratings of physician and nurse skill.
They also suggest that such training may offer a substantial competitive market
advantage, as well as improve the patients' perception of quality and outcome.
PMID- 10182932
TI - A cost-savings analysis of prenatal interventions.
AB - Proper prenatal care has long been established as the single most important
factor in improving both maternal and infant health (Henderson 1994) yet the
United States remains one of only two industrialized nations that have yet to
ensure universal healthcare for pregnant women (National Center for Farmworker
Health, Inc. 1997). Through clinical innovations, many progressive interventions
now available are not only medically effective but also financially prudent. This
study addresses the efficacy and feasibility and discusses the policy
implications of the following four prenatal programs: universal prenatal
screening for the human immunodeficiency virus, prenatal carrier screening for
cystic fibrosis, condition-specific care for pregnant diabetics, and prenatal
nutrition counseling. The healthcare community is challenged to expand the
breadth of routine prenatal care to include those services that are both
financially sensible and clinically imperative.
PMID- 10182933
TI - Alternative dispute resolution: methods to address workplace conflict in health
services organizations.
AB - As healthcare organizations become increasingly complex, healthcare
administrators and human resource managers face the cost and challenges of
employment-related disputes. Litigation and legal costs associated with
employment disputes are escalating at a significant rate. Additionally,
litigation procedures are drawn out and damage the employer-employee
relationship. Alternative dispute resolution (ADR) programs such as mediation and
arbitration alleviate the burden of litigation and preserve positive employment
relationships between the organization and its employees. A proposed ADR program
is presented is a guideline for health services organizations considering the
adoption of such programs.
PMID- 10182934
TI - NICHE (Nurses Improving Care to the Hospitalized Elderly) project helps improve
geriatric outcomes.
PMID- 10182935
TI - Be a leader, not a victim in changing access world. Need for separate department
may end.
PMID- 10182936
TI - Customer service principles expand within UTMB (University of Texas Medical
Branch).
PMID- 10182937
TI - Patient-centered philosophy at core of successful pain management program.
AB - In 1996, the American Nurses Credentialing Center in Washington, DC, recognized
the UC Davis Medical Center in Sacramento as a magnet nursing center of
excellence. The pain management program was cited as one of the distinguishing
activities that promotes quality of patient care services and development of
successful nursing strategies.
PMID- 10182938
TI - 'Prehab program' can slow down functional decline in geriatric patients.
AB - The following model was one of four recommended by Nurses Improving Care to the
Hospitalized Elderly (NICHE), a national initiative designed to help hospitals
prepare for the nation's burgeoning aging population. For more information on
other NICHE models, see the January issue of Patient-Focused Care and
Satisfaction.
PMID- 10182939
TI - Clerical, clinical changes increase nursing efficiency.
AB - Only six health care systems in the nation have received the Magnet Nursing
Services Recognition Award from the American Nurses Credentialing Center in
Washington, DC. This prestigious designation acknowledges quality of patient care
services and the development of successful, professional nursing practices and
strategies. Here is how one hospital used clerical staff to help it win this
award.
PMID- 10182940
TI - Simple solutions cut admission wait time.
PMID- 10182942
TI - Clinical decision making is at the point of service.
PMID- 10182941
TI - Patient-focused care model slashes bureaucracy.
PMID- 10182943
TI - Redesign calls for rethinking processes and revamping organizational culture.
AB - The very nature of redesign challenges traditional work roles and organizational
hierarchies. Even facilities with stellar reputations for clinical quality are
not immune to its challenges. Here's the story of the Cleveland Clinic
Foundation, where staff have experienced some of the same basic redesign problems
that have challenged lesser-known facilities.
PMID- 10182944
TI - Best care for the dying is listening to their needs.
AB - With the heated debate over physician-assisted suicide and other end-of-life
controversies, health care professionals may be overlooking a crucial element
that helps them navigate, or even calm, these stormy waters: patient-focused care
for those with life-threatening illnesses. With hospitals becoming true acute
care centers, the issues of providing care to these patients will grow in
importance. While the subject is uncomfortable, studies show health care has
ignored the issue for too long. And some have argued that the assisted suicide
debate is really a reaction to health care providers' inability to effectively
deal with the issues that surround care for the patient who is dying. The
following article provides you with some clues about where to start this effort
in your facility by looking at a landmark study that shows what these patients
and their families really want.
PMID- 10182945
TI - Improve satisfaction through better pain control.
PMID- 10182946
TI - New research report separates re-engineering reality from rhetoric.
PMID- 10182947
TI - Boomers give health care failing grade.
AB - In 13 more years, the first of the baby boom generation will turn 65, becoming
the heaviest users of the health care system. Do you know what the boomer
patients will want? And are you ready to satisfy them? In this first part of a
series on boomers and health care, we'll find out why boomers aren't happy about
the current health care system.
PMID- 10182948
TI - Are ED nursing staff levels under attack?
PMID- 10182949
TI - Have back-up plan to call in nurses.
PMID- 10182951
TI - Magnet recognition program gains reputation and stature with nurses.
PMID- 10182950
TI - NIOSH issues sharps box guidelines.
PMID- 10182952
TI - Offer complementary medicine to draw boomers.
PMID- 10182953
TI - On-call docs present EMTALA risks for the ED.
PMID- 10182955
TI - Think through issues in satisfaction survey change.
PMID- 10182954
TI - Cancer center focuses on treating the whole person, not just the disease.
PMID- 10182956
TI - Are they patients or customers?
PMID- 10182957
TI - Enterprise scheduling may improve patient access. 'Transparent' registration is
the goal.
PMID- 10182958
TI - Staff narratives perpetuate patient-focused values in face of rapid change.
PMID- 10182959
TI - Deciding to expand? Run the numbers. Internal benchmarking and redesign pay off.
PMID- 10182960
TI - Express unit cuts direct admit time drastically.
PMID- 10182961
TI - Teamwork, accountability cut discharge-to-bill time.
PMID- 10182962
TI - Feds respond to False Claims Act pressure.
PMID- 10182963
TI - House GOP seeks large tax cut, Medicaid cut.
PMID- 10182964
TI - New HHS organ transplant rule characterized as federal power grab.
PMID- 10182965
TI - The millennium bug: 18 months and counting down.
PMID- 10182966
TI - BBA (Balanced Budget Act) pumps prospective payment pipeline.
PMID- 10182967
TI - Back to basics.
PMID- 10182968
TI - Making preventive care initiatives work.
PMID- 10182970
TI - EBM (evidence-based medicine): what's new and what's on the Net.
PMID- 10182969
TI - Linking performance improvement and case management.
PMID- 10182971
TI - Targeting women's health preferences.
PMID- 10182972
TI - Breast Cancer Prevention Trial is a raging success.
PMID- 10182973
TI - A predictive model for management of patients with comorbidities.
PMID- 10182975
TI - Rescuing healthcare from the paper tiger.
PMID- 10182974
TI - Measuring the care of members with cardiac disease.
PMID- 10182976
TI - A continuum of care model that works.
PMID- 10182977
TI - Front attacks aim to parry managed care backlash.
PMID- 10182979
TI - Doing away with 'CRUD' (complexity, redundancy, unnecessary steps and delays)
saves one hospital $15 million.
PMID- 10182978
TI - Disease management improves patients' service perception along with care.
PMID- 10182980
TI - 'We need a diabetes check on aisle five, please'.
PMID- 10182981
TI - IT serves as safety net for compliance.
PMID- 10182982
TI - Consumer influence on healthcare reform.
PMID- 10182983
TI - Executives see little use for SSOs (single specialty organizations,) so far.
PMID- 10182984
TI - Physicians need numbers to see benefit in gamble of accepting risk.
PMID- 10182985
TI - Properly compensating network physicians.
PMID- 10182986
TI - United HealthCare/Humana merger creates new managed care challenges for
hospitals.
PMID- 10182987
TI - Hospital compliance on a budget.
AB - Community and rural hospitals are among the last to jump aboard the compliance
program bandwagon. For many, it boils down to a belief that a plan either is not
necessary or not affordable. Ellen Beck profiles the special issues that smaller
hospitals face amid government investigations into Medicare/Medicaid billing
fraud.
PMID- 10182988
TI - Knowledge management is new competitive edge.
AB - Managing knowledge is emerging as the latest business strategy to get ahead of
the competition. In the process of developing knowledge management systems,
executives are increasing their awareness and understanding of organizational
dynamics, collaboration, corporate learning and knowledge management technology.
But Donald E.L. Johnson writes that health care executives must buy into and
understand collaboration and corporate learning before they tackle knowledge
management.
PMID- 10182989
TI - Don't just deliver value, demonstrate it.
AB - Except for the actual duration of an outpatient visit or inpatient stay,
hospitals "own" no patients at all. How can population-based performance measures
be calculated for a hospital that address the value it has delivered to its
patients over the past year?
PMID- 10182990
TI - Government officials redefine use of False Claims Act to combat fraudulent
hospital bills.
AB - The Dept. of Justice and the Dept. of Health and Human Services Office of
Inspector General have issued new guidelines for using the False Claims Act to
prosecute hospitals that fraudulently bill Medicare. Ellen Beck explains the
changes and why the American Hospital Association calls the more lenient use of
the FCA a "positive first step" toward acknowledging that the act is being used
improperly.
PMID- 10182991
TI - HealthSouth acquisitions throw another log on the burning market for ambulatory
centers.
AB - In late May and early June, HealthSouth Corp. announced two major purchases of
ambulatory surgery centers from Columbia/HCA Healthcare Corp and National Surgery
Centers. Joanne Todd profiles HealthSouth's recent $1 billion spending spree and
what it tells us about the already booming ambulatory surgery industry.
PMID- 10182992
TI - The strategy checkup: making sure that your present is what you envisioned in the
past.
AB - Health care is changing at a pace that the industry has never seen. But health
care consultant Ellen Goldman says that organizations would be wise to
occasionally slow down, relax, reflect, and ask, "Are we on the right track?" She
outlines her methods for a strategic checkup so health care organizations can
make sure that their present is the future they planned for in the past.
PMID- 10182993
TI - Developing a successful product line strategy.
AB - By looking beyond traditional organizational boundaries and integrating the
clinical and administrative activities from a system perspective, providers and
their partners will improve their ability to compete by providing better, more
effective care.
PMID- 10182994
TI - Cook County enters partnerships to expand community primary care capacity.
AB - A need for greater community access to primary care prompted the Cook County
Bureau of Health Services in Chicago to seek partnerships with two private, not
for-profit hospitals. Bethany Hospital, St. Anthony Hospital and the Bureau have
assessed the potential for meeting one another's needs, providing complementary
components to a partnership.
PMID- 10182995
TI - Using preventive care to decrease hospital admissions of pediatric patients.
AB - A new study shows a correlation between preventive care and a drop in avoidable
hospitalizations. Richard Frye, Ph.D. profiles the Maryland Access to Care
program, which achieved the results, and explains how it helped reduce pediatric
hospital admissions.
PMID- 10182996
TI - Medicaid MCO members require extra attention to avoid "preventable diseases".
AB - As more Medicaid recipients move into managed care plans, providers and payers
are taking a closer look at Medicaid patients and their special needs. They're
finding that interventions with a strong focus on patient education and community
support are highly successful at helping Medicaid recipients avoid so-called
preventable diseases.
PMID- 10182997
TI - Hospitals need to help Medicare HMOs.
AB - Many of the health maintenance organizations that rushed to create Medicare
products are bailing out of their Medicare contracts. Donald E.L. Johnson writes
that Medicare HMOs face market and government challenges, and hospitals should
try to anticipate HMOs' next moves and have responses ready.
PMID- 10182998
TI - Texas hospital complex trains security officers to deter violence.
PMID- 10182999
TI - An interview with: Joseph R. Coppola on Johns Hopkins security four years later.
PMID- 10183000
TI - How hospital has integrated its fire safety and security systems.
PMID- 10183001
TI - Matching security to expansion: experiences of Las Vegas hospitals.
AB - Although in most parts of the country healthcare officials are noting a trend for
hospitals to merge, consolidate, or even shut down because of financial
constraints and increasing competition from factors such as managed care, Las
Vegas, NV, is witnessing a growth in new construction and expansion of hospital
facilities. In this report, we'll examine recent activities there and the
challenges currently being faced by security in protecting patients, visitors,
and staff.
PMID- 10183002
TI - Digital television broadcasting.
PMID- 10183003
TI - Media relations. As seen on TV.
PMID- 10183004
TI - Pharmacy. Shop talk.
PMID- 10183005
TI - Child mental health services. Side by side.
AB - The appointment of a primary care mental health worker can relieve pressure on
child and adolescent mental health services. In one health authority, GP
practices with access to a liaison clinic run by a primary care mental health
worker referred a third fewer cases to child and adolescent mental health
services than practices without such access. Referrals by these practices were
more likely to be assessed as appropriate and as high priority.
PMID- 10183006
TI - NHS boards. It takes two to tango.
AB - Successful chair-chief executive relationships depend on a 'no surprises' rule.
The fact that a chair can terminate a chief executive's contract with little
reference to anyone else is a weakness in the system. When a relationship breaks
down it is usually for personal rather than formal reasons.
PMID- 10183007
TI - Primary care groups. Going through the change.
AB - The successful establishment of primary care groups will demand sensitivity from
managers. It is important to acknowledge, and mourn, what is being lost by ending
the old arrangements. People do not resist change itself, but the losses and
endings it involves. Despite the tight timetable, management should be
participative rather than directive.
PMID- 10183008
TI - Buildings. Open doors.
PMID- 10183009
TI - The demographic impact on ambulatory pharmaceutical expenditure in Belgium.
AB - It has become customary in our society to attribute the rise in health care
expenditure to a large extent to the aging of the population. The Belgian
Institute of Health Economics (BIGE-IBES) finalised a study to measure the impact
of the demographic trend on public spending for ambulatory pharmaceuticals. The
results show that the changes in age structure as such have a relatively small
impact on health care expenditure. Over the period 1986-1996 an annual growth of
+0.73% was observed, while total public spending showed an annual average
increase of +6.2% (in constant francs 1996). This first static demographic impact
will become +0.75% per year for the next decade 1996-2006. It is, however,
possible to calculate the extent to which per capita expenditure envolved
differently according to age group: over 1986-1996 expenditure for the elderly
was rising more sharply than for the younger age groups. This leads to a second
dynamic demographic impact which will cause an annual growth rate of +1.91% for
the next decade, according to the working hypothesis put forward. This growth
rate is to be compared with the authorized budgetary increase of +1.5% per year
(inflation excluded), according to the EU-Maastricht quotes..., and it does even
not take into account the other increasing factors as technological innovation
and epidemiological needs.
PMID- 10183010
TI - Risk-adjusted capitation payments: developing a diagnostic cost groups
classification for the Dutch situation.
AB - In many countries market-oriented health care reforms are high on the political
agenda. A common element of these reforms is that the consumers may choose among
competing health insurers or health plans, which are largely financed through
premium-replacing capitation payments. Since 1993, Dutch sickness funds receive
risk-adjusted capitation payments based on demographic factors. It has been shown
that the predictive accuracy of a demographic capitation model improves when it
is extended with diagnostic information from prior hospitalizations, in the form
of Diagnostic Costs Groups (DCGs). In this study a DCG classification is
developed using Dutch cost data of sickness fund members of all ages. The study
also dealt with the question of how to handle high discretion diagnoses. For the
Dutch situation high discretion diagnoses may be defined as those diagnoses for
which day case treatment is a possible alternative for a hospital admission.
Grouping persons with a hospital admission for high discretion diagnoses together
with people without an admission resulted in a slight reduction of the predictive
accuracy of the DCG model. Adequate risk-adjustment is critical to the success of
market-oriented health care reforms. The use of diagnostic information from prior
hospitalizations seems a promising option for improving the capitation formula.
PMID- 10183011
TI - The role of quality standards--accreditation in redressing asymmetry of
information in health care markets.
AB - Asymmetry of information presents major difficulties for the efficient operation
of markets in health care. The use of accreditation schemes may reduce these
difficulties by enhancing the availability of reliable, accessible information on
aspects of service quality considered important by service users and their
agents. The UK's Patients' Charter with its associated Charter Marks has the
potential to perform such a function in respect of inpatient services. In as much
as it refers to aspects of service valued by service users which are specified in
contracts by service procurers and appear not to be negatively correlated with
other aspects of service quality, it can be seen to provide unambiguous signals
of service quality. Given the Charter is currently under review, it seems
appropriate that such attributes are borne in mind by policy makers in their
deliberations as to its future.
PMID- 10183012
TI - Alcohol advice in primary health care--is it a wise use of resources?
AB - Many attempts to calculate costs caused by the use of alcohol in accordance with
the cost-of-illness method have been reported in the literature. However, in a
decision-making perspective and with a focus on what possible interventions to
undertake, cost-benefit or cost-effectiveness studies are more useful. In this
study the cost-effectiveness of advice aimed at reducing 'heavy' drinking to
'moderate' drinking is calculated. Results from controlled trials, showing the
short-range effects of advice, are combined with observations from long-term
epidemiological studies showing the association between alcohol consumption and
total mortality. This study shows that advice from primary health care staff has
a potential to be a very cost-effective means of intervention. The crucial point
seems to be the number of people that makes durable changes in consumption. If
about 1% make lasting changes a brief intervention is relatively cost-effective
(20,000 ECU/YLS), and if about 10% change resources will be saved in health care.
Important effects such as increased quality of life and decreasing production
losses are not taken into account.
PMID- 10183013
TI - The importance of developing an informatics framework for mental health.
AB - Though mental health services are important in human terms, and account for a
tenth of health expenditure, they are not well served in informatics
developments. There are no specific mental health components in the European
Union's health telematics programmes, and there is similar under-representation
in national programmes. Yet telematics has much to offer mental health services
and their management, and can address directly current service anxieties.
Telematics concepts which could benefit mental health include integrated, multi
disciplinary records, real-time multi-site record access, and structured
programmes to plan, schedule, and monitor care delivery. The power of information
systems to sort data, and to represent them graphically, can sift like data items
from complex records, and can present them in displays which highlight their
significance. Above all, quality of care can be enhanced by monitoring, and by
improved outcome measurement. However, a planned programme of research and
development is needed, to relate and adjust current health informatics techniques
to the special attributes of mental health. The World Health Organisation has
identified the potential of such a programme, but greater vision and commitment
is needed at policy level if mental health services and patients are to receive
the benefits from health informatics which are available to the physically ill.
PMID- 10183014
TI - Economic evaluation of programmes aiming at eradicating infectious diseases.
AB - The subject of this article is to discuss the global and regional economic
aspects of programmes for eradicating infectious diseases. The perspective on the
issue is that scarce health care resources should be employed in the best
possible way. The task is then to examine what the best possible use might be. A
starting point is by asking the relevant policy questions attached to
eradications: Is there a suitable technique, what are the costs, and what are the
benefits? Of particular importance is the opportunity cost of using resources on
eradication when other health care problems may require more urgent donation of
resources. The paper attempts to set up a generic model for economic evaluation
of eradication programmes. But, as there are many different treatment strategies
varying from one country to another, such a generic model may need modifications
to suit a particular strategy. However, the paper is contextual and should only
be viewed as guidance for those wishing to conduct an economic analysis of
eradication programmes, or as a initiative to create discussion among health care
decision makers.
PMID- 10183015
TI - Eye spy. Check crime at the door. Put your money on access control technology.
PMID- 10183016
TI - Outsourcing is in. Three Cs make it a good bet.
PMID- 10183018
TI - Pacemaker prices decline, but gently.
PMID- 10183017
TI - Crime busters: tips on how to prevent on-the-job violence.
PMID- 10183019
TI - Inventory: it's what's upstairs that counts.
PMID- 10183020
TI - Purchasing execs look to future with optimism.
PMID- 10183021
TI - Capital equipment buy should be part of strategic plan.
PMID- 10183022
TI - Growing demand yields 'friendlier' blood sugar monitors.
PMID- 10183023
TI - COHR rejects 'bottom fishing' offers for its GPO.
PMID- 10183024
TI - Hip implant prices show modest drop.
PMID- 10183025
TI - More hospitals plugging into radiology networks.
PMID- 10183026
TI - Consolidated GPO set to end year with new portfolio.
PMID- 10183027
TI - GPOs: still viable, but their role is changing.
PMID- 10183028
TI - Hospitals cite co-op rules, not sale, in MedEcon defection.
PMID- 10183029
TI - Joint Commission on Accreditation of Healthcare Organizations. Public information
policy. The accreditation cycle: official accreditation policies and procedures.
PMID- 10183030
TI - Joint Commission to offer international accreditation services.
PMID- 10183031
TI - Equivalent sources for primary source credentials verification.
PMID- 10183032
TI - New integrated survey process for small hospitals introduced.
PMID- 10183033
TI - Unaccredited component organizations' sampling methodology revised.
PMID- 10183034
TI - New examples address hospital's listing of Medicare-certified home health
agencies.
PMID- 10183035
TI - Guidance from IRS. Agency to release intermediate sanctions regulations.
PMID- 10183037
TI - Debating the safety net. Coalition says private hospitals provide more than half
of uncompensated care.
PMID- 10183036
TI - Counsel or co-conspirator? Inclusion of lawyers in K.C. indictment raises
questions.
PMID- 10183038
TI - Widening rift. Docs battle with Ohio hospital over independence.
PMID- 10183039
TI - AHERF files for Chapter 11. Action may precede sale of nine hospitals to
Vanguard.
AB - Allegheny Health, Education and Research Foundation, one of the nation's brashest
not-for-profit health systems, last week filed for Chapter 11 bankruptcy
protection. The last-ditch move will allow Pittsburgh-based AHERF, which is $1.3
billion in debt, to restructure money-losing operations and pave the way for the
sale of its nine Philadelphia-area hospitals. But the repercussions of the filing
will be felt well beyond the state of Pennsylvania.
PMID- 10183040
TI - Columbia: year in review. Federal probe, new management leave their marks.
PMID- 10183041
TI - Taking care of their own. When industries face legislative regulation, self
protection outweighs self-policing.
PMID- 10183042
TI - Not so fast ... pay increases slow.
PMID- 10183043
TI - Trouble at home. Some hospitals spin off their home health agencies.
PMID- 10183044
TI - To bid or not to bid. Novation redesigns contracts for public-private needs.
PMID- 10183045
TI - A whole new ballgame. PPMs strike out on Wall Street but score with banks.
PMID- 10183046
TI - A shot at immunity. Bill allows independent docs to negotiate collectively.
PMID- 10183047
TI - A one-hospital town. Asheville, N.C., facility to sell out to its large partner.
PMID- 10183048
TI - Still climbing. MedPAC: despite freeze, Medicare margins to hit record.
PMID- 10183049
TI - Surprise inspection. AHERF's financial woes prompt visit by JCAHO.
PMID- 10183050
TI - The buck stops here.
AB - As Allegheny Health, Education and Research Foundation muddles through its high
profile bankruptcy reorganization, the spotlight of public scrutiny is now
shining brightly on the system's board members, who were supposed to act as
guardians of the not-for-profit system. "When things fall apart, the board
members usually take the heat," says one governance expert. "And they should take
the heat, since they are the final buffer."
PMID- 10183051
TI - Risk without reward. Health plan liability would increase lawsuits and costs,
wouldn't help patients.
PMID- 10183052
TI - Growing like wild. Hospitals enter booming assisted-living business.
PMID- 10183053
TI - A new kind of ownership. Theorist suggests new 'community service' tax status.
PMID- 10183054
TI - HIMSS to pack them in. Exhibitors clamoring for space at next convention.
PMID- 10183055
TI - Good news, bad news. BJC earns coveted rating, but outlook downgraded.
PMID- 10183056
TI - AHA taps trustee to chair its board.
PMID- 10183057
TI - GAO: HCFA failed to sanction Calif. nursing homes.
PMID- 10183058
TI - Looking for trouble. State, federal investigators seek tips on problem HMOs.
PMID- 10183059
TI - BJC chief to step down. Brown will resign to focus on AHA chairman post.
PMID- 10183060
TI - Uncertainty rocks HMO industry. United loss threatens Humana merger.
PMID- 10183061
TI - Not-for-profits get IRS help.
PMID- 10183062
TI - On the rebound. GWU hospital realizes benefits of investor ownership.
PMID- 10183063
TI - Problem takeoff. Calif. program for low-income kids hits some snags.
PMID- 10183064
TI - Y2K hits CIO's hot button. Millennium bug invades IS priorities, survey shows.
PMID- 10183065
TI - Too hot for PARCA (Patient Access to Responsible Care Act). Despite coalition's
support, Norwood bill stalls.
PMID- 10183066
TI - Do what suppliers do.
PMID- 10183067
TI - Training strategic thinkers.
PMID- 10183068
TI - The countdown continues. Hospitals and healthcare systems are racing the clock to
determine the severity of the year-2000 bug infestation.
AB - As the clock continues to tick toward the new millennium, healthcare systems are
racing to determine the severity of the year-2000 bug infestation. One system
putting its computers and medical devices to the test so far has found a 20%
failure rate. The system also has found that some devices just can't be tested.
As one expert said: "This is not a technology problem; it's a management
challenge."
PMID- 10183069
TI - Market sizzles in Raleigh-Durham. Competition is hot for a piece of the action.
PMID- 10183070
TI - Home health 'guidelines' include mandates.
PMID- 10183071
TI - Black and blue. Calif. systems, Blue Cross settle bruising contract disputes.
PMID- 10183072
TI - Bottom-up innovation. Venture capital change may foster entrepreneurial growth.
PMID- 10183073
TI - Picking up the pieces. United, Humana cope with fallout from failed merger.
PMID- 10183074
TI - AHERF's Philly hospitals to go up for auction.
PMID- 10183075
TI - Another deal unravels. Saint Vincent in Erie, Pa., balks at antitrust agreement.
PMID- 10183076
TI - The IRS' list of no-nos. Manual tells joint ventures how to avoid trouble.
PMID- 10183077
TI - Refocus on care. AHA finds consumer concern about profit motive.
PMID- 10183078
TI - AHA, Healthcare Forum in merger talks.
PMID- 10183079
TI - Classic Beltway battle. Falloff in home-care spending leads to finger-pointing.
PMID- 10183080
TI - Hospitals cry foul. Rules would force double changes in surgery billing.
PMID- 10183081
TI - Survival of the sickest. Organ allocation should be based on patients' medical
need, not location.
PMID- 10183082
TI - Dueling for public support. Americans go gunning for managed-care plans as they
stand by their docs.
AB - If healthcare were a movie western, Americans would costume their doctors in
white hats and HMOs in black hats. They'd cast hospitals as the Wild West
merchant watching the gunfight from the doorway of his shop and themselves as the
frightened townspeople waiting for the smoke to clear. That's the simple version
of the complex portrait of U.S. public opinion on healthcare as painted by
polling firms and survey organizations.
PMID- 10183083
TI - AMA adds consulting link. New alliance will tap extra revenues, provide
referrals.
PMID- 10183084
TI - Survey identifies a missing link. Doc groups aren't tying pay and performance.
PMID- 10183085
TI - On the home front. Deadlines set for home-care agencies' data reporting.
PMID- 10183086
TI - Bidding for business. Bond sales getting more competitive; on-line auctions among
the options.
PMID- 10183087
TI - S&P's prognosis: managed care will gain in health.
PMID- 10183088
TI - R.I. deal flunks test. Asset-transfer law invoked to block system's affiliation.
PMID- 10183089
TI - Fraud probes target HMOs. States attack plans for false marketing, care denials.
PMID- 10183090
TI - Third-party trouble. Billing firm probes net big provider fraud settlements.
PMID- 10183091
TI - Montana sours on managed care.
PMID- 10183092
TI - Confidentiality casualty. Patient billing printouts released in Kansas fraud
case.
PMID- 10183093
TI - 1998 up & comers .
AB - Modern Healthcare honors this year's "Up & Comers," 11 young healthcare
executives all 40 or under who already have made their mark in the healthcare
industry. "As remarkable as their achievements are today, the potential for what
they may do tomorrow is staggering," says Jordan Hadelman, whose firm,
Witt/Kieffer Ford, Hadelman & Lloyd, was involved in the nominating process.
PMID- 10183094
TI - HMOs rule in Boston market. But costs, utilization are high.
PMID- 10183095
TI - Poor prospects. HCFA: some outpatient departments will lose under PPS.
PMID- 10183096
TI - Doc losses may not affect hospital rating.
PMID- 10183097
TI - A slow trickledown. Data on efficacy of beta blockers belatedly spur use.
PMID- 10183098
TI - More financial pain. Market gyrations deal another blow to healthcare stocks.
PMID- 10183099
TI - HCFA announces discharge billing changes for postacute care transfers.
PMID- 10183100
TI - Disaster recovery planning: preventive medicine for information technology.
PMID- 10183102
TI - Trustees in transition. Survey shows it's time for boards to get with the program
-or get eaten by the competition.
AB - National surveys of hospital and system trustees, conducted by the AHA and Ernst
and Young LLP, show that boards are evolving dramatically. And those that aren't
don't stand a chance in the leadership race for the 21st century.
PMID- 10183101
TI - Principle-based governance: an approach for integrated board leadership.
PMID- 10183103
TI - High noon for community mission.
AB - When seeking to merge or affiliate, trustees often lose sight of mission. Letting
egos and turf problems get in the way of strategic needs and compatible missions
will shoot down a successful venture as effectively as an evil gunslinger on the
frontier.
PMID- 10183104
TI - Dying well in America: what would success look like?
PMID- 10183105
TI - Governance. Conflict can lead to success.
PMID- 10183106
TI - Niche players: your next challenge.
PMID- 10183107
TI - Stand and deliver.
PMID- 10183108
TI - Rebuilding the lives of the homeless.
AB - Drawing on the community's health care, business, and social service resources,
the I.M. Sulzbacher Center for the Homeless in Jacksonville, Fla., goes beyond
just meeting the food, shelter, and medical needs of the city's destitute. As one
center resident puts it: "Homelessness is feeling like you're less of a human
being. I really don't feel homeless; I feel like this is my home."
PMID- 10183109
TI - They HAVE (Hospital Awards for Volunteer Excellence) what it takes.
PMID- 10183110
TI - Take a spin on the information superhighway: an Internet primer.
PMID- 10183111
TI - Volunteer management and the Internet: ASDVS's (American Society of Directors of
Volunteers Services) new Web page.
PMID- 10183112
TI - A community plunge puts you in touch with real people, real needs.
PMID- 10183113
TI - The other end of the ripple effect: creating patient satisfaction.
PMID- 10183114
TI - The power to wait. Teens make sexual abstinence 'cool' to pre-teens.
PMID- 10183115
TI - The price of teen pregnancy.
PMID- 10183116
TI - Ethics for medical group managers: patient-centered or bottom-line?
AB - Many physicians hire financial directors and accountants to manage their bottom
line. While most of us had courses in financial and operations management, ethics
was not a major part of the curriculum. This professional paper will define
several ethical theories. After applying these to three moral issues--marketing,
fee setting and rationing--it will outline a values clarification plan and
finally will conclude by providing a framework for making moral decisions,
realizing, of course, that the study of ethics offers no right or wrong
responses.
PMID- 10183117
TI - Marketing specialty physician services.
AB - Physicians take into account many factors when making referral decisions,
primarily provider expertise, good communication and good patient care. This
professional paper will show that provider expertise and patient care are the
most important factors in referral decisions, and that physicians rely primarily
on direct experience for the information necessary to make a referral choice.
PMID- 10183118
TI - Service management.
AB - Superior service is the outcome of a dedicated planning methodology. Medical
groups that plan and manage for patients' service needs will achieve market
differentiation, enjoy enhanced levels of staff development and motivation and
improve long-term financial performance. Medical groups that ignore the
importance of service excellence will find themselves trailing those groups that
provide superior service to their patients.
PMID- 10183119
TI - Recruiting physicians for rural states: a comparative, socio-economical model.
AB - Recruitment of physicians to rural states is complicated by several barriers
precipitated by non-metropolitan locations. These constraints need to be
addressed and put into proper perspective in order to attract the interest of
potential candidates. This case study addresses our efforts to educate the
candidate regarding the potential foregone, social and economical practice
opportunity benefits associated with our rural location.
PMID- 10183120
TI - Expansion of a hospital-based service systems to support a satellite clinic
network.
AB - The activities documented in this case study arose as a result of a decision by
hospital administration that it would be more cost effective to provide services
with in-house departments rather than through outside vendors. The clinic
administrator was charged with coordinating the implementation of these services
in the clinics by the hospital support departments. This article will explore
service delivery problems and resolutions.
PMID- 10183121
TI - Practice management education--are residency programs properly preparing
physicians for the 21st century?
AB - Several surveys indicate that third-year physician residents and recent graduates
felt that their training in practice management skills was inadequate and that
they felt unprepared in this area. This professional paper will present a
discussion of residency education and the current complex health care
environment. It will also describe a three-year comprehensive curriculum in
practice management which can be incorporated into the programs.
PMID- 10183122
TI - Ergonomics: the investment of the '90s.
AB - Repetitive strain injuries, headaches and backaches are growing faster than any
other occupational injury as a by-product of our computerized work environment.
Many of these injuries can be avoided in an ergonomically designed office. This
professional paper will provide a summary reference in the correct design of a
"human-friendly" medical office group.
PMID- 10183123
TI - The development of a women's health center in an academic health center.
AB - Women's health needs have been a special focus of health care for more than a
century. In the early 1970s, a segment of the women's market began seeking
changes in the health care system. Since then, the emergence of women's health
centers has been a nationally growing trend. This professional paper will address
the various elements in designing a women's health center in an academic health
setting, beginning with the development of a concept and needs assessment and
ending with the influence a women's health center has on health care for others.
PMID- 10183124
TI - Marketing medical services to an aging America.
AB - Consumers over age 50 currently comprise 40 percent of consumer demand. Medical
services provided in the group practice setting must be structured to accommodate
the unique needs of their increasing number of elderly patients According to this
professional paper, the development of a marketing plan will provide a strategy
that will keep the medical group competitive among older consumers.
PMID- 10183125
TI - The unraveling of a joint venture.
AB - An orthopedic group that recently moved to a new location needed to boost its
image. In an effort to gain control of the market, and increase its referral
base, the group tried to turn several local health clubs into sports medicine
clinics. This case study details the time, money, efforts and, finally, the
lessons learned from this unsuccessful venture.
PMID- 10183126
TI - A novel method for storage of medical records and documents.
AB - Many medical groups have a problem storaging and managing inactive medical
records. The storage process involves selecting the records from inactive status,
moving the records to storage and retrieving them if the patient is re
established. Many groups simply run out of storage space and are in need of an
efficient and cost-effective way to manage this problem. This case study will
show that an optical storage system provides a cost-effective method of archiving
medical documents that can be easily indexed and retrieved.
PMID- 10183127
TI - Is bigger really better? An analysis of economies and diseconomies of scale in
orthopaedic group practice.
AB - As administrators, we continually strive to compare our group's performance to
accepted standards of cost and production. In making comparisons to national
norms, it is important to understand the statistical sample of groups from which
these norms are drawn. Therefore, differentiations in the size of a group alone
may have predisposed a group to either favorable or unfavorable comparisons to
national standards. This professional paper was written in order to investigate
the relationship between group size and measures of performance.
PMID- 10183128
TI - Electronic patient records: cost savings, efficiencies and competitive strategies
for specialty physician groups.
AB - Knowledge is power. Sharing information about patients and knowledge about
practice guidelines with allied physicians through the electronic patient record
can help strengthen and maintain referral relationships. Electronic patient
records can support specialty physicians in managing care across the continuum.
As this professional paper suggests, organizations should be open to the use of
cutting-edge technologies as long as there is a compelling business reason for
introducing them. Specialty practices that want to successfully meet the future
certainly have compelling business reasons for embracing the electronic patient
record.
PMID- 10183129
TI - CHINs: information superhighway or unpaved byway?
AB - In all successful systems it is the relationship--both formal and informal--that
define how well organizations run and how they create value for their customers.
Information systems' real benefit, therefore, is to add value to those
relationships. No matter if the original business intent of the system was to
speed delivery, cut costs, improve quality or provide integration of services,
information systems' value resides in their ability to get the right people (not
the computers) to talk to each other more efficiently and effectively. Take this
simple premise, apply it to the creation of CHINs and ask, "What relationships
matter and how can CHIN participation most effectively enhance those
relationships for our medical group?" The answer, combined with the need to
deliver high quality, lowest possible cost health care, is the goal of CHINs, as
described in this professional paper.
PMID- 10183130
TI - The impact of managed care on academic Ob/Gyn departments.
AB - In order to lead an organization into the 21st century. Ob/Gyn administrators and
chairpersons must understand managed care models and markets. With a basic
understanding of the history of managed care and its impact, administrators and
physicians will be better prepared to position their organizations to maximize
opportunities for contracts with managed care organizations or change operations
to respond to capitation and other financing methodologies. There are no
"cookbooks" available, but health care leaders can learn to recognize a broad
range of markets and strategic choices. The strategies discussed in this
professional paper identify and should help Ob/Gyn departments survive and thrive
in the future.
PMID- 10183131
TI - Ambulatory surgical center: developing a health care opportunity.
AB - The objectives of this article include a review of the origin, reasons and
rationale for developing an ambulatory surgical center (ACS) and the
developmental process. In addition, opportunities and limitations are discussed
in different developmental stages. Licensing, personnel and day-to-day operations
are examined, and finally, impacts, implications and the future of ASCs are
discussed.
PMID- 10183132
TI - Development of a pre-employment testing program in medical group practices.
AB - Pre-employment testing requires rigorous groundwork which many managers may not
be willing to do, nor pay a professional to do for them. The benefits, though,
have been documented in a number of studies which have shown pre-employment
testing to be a beneficial and cost-efficient part of the selection process. Pre
employment testing will not supplant traditional selection processes such as
interviewing and reference checks, but rather will enhance the selection process
and reduce costs associated with turnover, as this professional paper discusses.
PMID- 10183133
TI - Coping with uncertainty: use of sensitivity and scenario analysis in the
evaluation of financial and operational risks associated with capitation
contracting.
PMID- 10183134
TI - The Internet: current status and future implications for health care
administrators.
PMID- 10183135
TI - Exploring the use and effectiveness of behavior style analysis tools in the
medical practice.
PMID- 10183136
TI - The evolving role of public health in an era of health care reform: opportunities
for collaboration.
PMID- 10183137
TI - Cutting edge Internet teleradiology from nine leading vendors.
PMID- 10183138
TI - International telemedicine: a time to be proactive.
PMID- 10183139
TI - Video publishing.
PMID- 10183140
TI - Telemedicine on top of the world (almost).
PMID- 10183142
TI - West Texas community gets school-based telemedicine clinic.
PMID- 10183141
TI - The wireless alternative to traditional wired networks.
PMID- 10183143
TI - The leaders: U.S. programs doing more than 500 interactive consults in 1997.
PMID- 10183145
TI - 'The noble language of the eye'. Honolulu ophthalmologist uses telemedicine
technology to teach tear duct surgery.
PMID- 10183144
TI - Corrections-based telemedicine programs top most-active list.
PMID- 10183146
TI - Prison telemedicine to Stringtown.
PMID- 10183147
TI - Tele-ophthalmology: a tale of seven programs.
PMID- 10183148
TI - Leadership and Public Health, Part II: Leading Change.
PMID- 10183149
TI - The Pope, hot pavement, and public health.
AB - The author recalls his first days and weeks as Director of Health for the City of
San Antonio and Bexar County, Texas. The article details some of the observations
made by the author as he developed a computerized immunization registry.
PMID- 10183150
TI - Public health leadership in five Kentucky Appalachian counties.
AB - This article reviews the steps taken by the Gateway District Health Department
(consensus building, stakeholder analysis, and strategies) in the development of
an integrated health/mental health services delivery program for families and
children in five elementary schools located in two remote Appalachian counties of
eastern Kentucky, the Rural Outreach Program for Elementary Students (ROPES).
Though several problems in achieving this collaborative effort are described,
"turf" and "trust" were never issues because of a 10-year history of
collaboration between the health department, provider agencies, and the schools.
PMID- 10183151
TI - Repositioning a state health agency in an era of change through developing the
internal customer: a case study in leadership.
AB - There is strength in maintaining a public health system that has been a stable
force in the health care system for several decades. The real challenge is
knowing how and when to make appropriate changes without destroying those
elements that work to benefit the public. This article describes one state's
approach to managing change and discusses the practical lessons learned from the
experience.
PMID- 10183152
TI - Business prospective: a complement to a successful public health agenda.
AB - Business planning is an analytical and practical exercise that will help better
understand your organization's position and capabilities with regard to the
competitive market place. This clarification will help set direction referencing
an organization's mission, alternative service delivery options and managed care
network opportunities. The Bergen County Department of Health is an organization
in transition, building capabilities and credibility to assume leadership
responsibilities in the development of a sustained Public Health infrastructure.
In addition, the department is attuned to the changing health care industry's
responsibility and incentives, is actively pursuing appropriate service delivery
roles as a complement to the county-wide community health system capacity.
PMID- 10183153
TI - Development of a community health service: a unique collaborative alliance.
AB - This case study describes the development of a public health satellite facility,
the Health Source of Grandview, Missouri, a collaborative alliance sponsored by a
public teaching/community medical center and a religious-sponsored community
medical center. The needs and alternative solutions are examined and planning
processes are discussed, including the issue of community needs and values as
well as roadblocks and barriers to collaboration, and how this model meets the
criteria for the new paradigm of community collaboration and partnership espoused
by so many in this era of health care reform.
PMID- 10183154
TI - Applying systems thinking to public health leadership.
AB - A review of the public health literature reveals a dearth of research that
focuses on applying management theories to public health work. This article
applies systems thinking to public health practice. A sample of health officers
and health department executives were asked to identify the key attributes of the
most important problem they faced in their work in the last week. Problems
involved an average of four other organizations, and most required two to six
months to be resolved. Most decisions were expected to result in new problems.
Several cases are presented as examples. Implications for future research,
practice, and training are discussed.
PMID- 10183155
TI - The education of local health department top executives.
AB - An analysis was done on the educational backgrounds of current top agency
executives of U.S. local health departments (LHD), using the National Association
of City and County Health Officials 1992-1993 national survey of LHDs as the data
source. Nurses are often the executive in jurisdictions with less than 50,000,
while executives of jurisdictions with more than 250,000 are predominantly
physicians. Overall, 78 percent of LHD executives have no formal public health
training, and executives of larger jurisdictions are more likely to have a public
health degree. Because a majority of executives lack formal training
opportunities for them need major expansion. Particular emphasis should be placed
on expanding short-term opportunities such as state-based leadership and distance
based learning programs.
PMID- 10183157
TI - Inner world to the future: leaders' perspective on the future.
AB - "Academic Perspectives" is a column within the Journal of Public Health
Management and practice that examines the linkages between academic public health
and practice. Readers of JPHMP are encouraged to contribute to this feature.
Contact column editor: Louis Rowitz, PhD, Deputy Director, Center for Public
Health Practice, School of Public Health, (M/C 922), University of Illinois at
Chicago, 2121 West Taylor Street, Room 206, Chicago, Illinois 60612-7260.
PMID- 10183156
TI - A successful, preventive-oriented village health worker program in Hebron, the
West Bank, 1985-1996.
AB - Village health rooms (VHRs) were established in villages with no on-site health
facilities in the Hebron District of the West Bank, beginning in 1985. By 1991,
the program served a total population of 40,000 in 49 VHRs and by the end of 1996
covered 69 villages in Hebron and 20 in other districts that were previously
served by visiting vaccination teams and nearby clinics. The VHRs provide close
contact with the population of mothers for well child and pregnancy care, health
education and provide visiting doctor/nurse teams for backup services and
supervision. Data on coverage, utilization, costs, and outcome measures are
presented. The program is accepted and grows despite adverse social and political
conditions.
PMID- 10183158
TI - Building a statewide coalition for tobacco control, 1993-present.
AB - In 1993, Maryland (a state with one of the highest cancer rates) had no organized
agenda for tobacco control. Dr. Wasserman's call to action at an annual
conference sparked the beginning of a statewide coalition, Smoke Free Maryland.
Through Dr. Wasserman's personal allegiance to focusing the coalition on a set of
principles, an effective strategy was mapped out for tobacco control. The
coalition's efforts brought success in legislative advocacy and regulation
change. Today Marylanders are protected by a workplace smoking ban, and have laws
in place designed to restrict minors' access to tobacco.
PMID- 10183159
TI - Essential public health services: myth or reality.
PMID- 10183160
TI - Flexibility in measurement of public health performance.
PMID- 10183162
TI - Translating maternal and child health essential public health services into
practice: current status and future challenges.
PMID- 10183161
TI - Typology of local health departments based on maternal and child health core
functions.
AB - A survey of Missouri local health departments (LHDs) was conducted to measure
core public health functions within maternal and child health (MCH). Measurement
was based on a prior key informant study that defined each core function as a set
of specific MCH activities, programs, and services. The 59 items in the survey
operationalized these activities and enabled the creation of summary scores for
assessment, policy development, and assurance. Participation included 93 of the
112 Missouri LHDs (83%) in 1995. Reliability coefficients for the summary scores
ranged from .83 to .92. Cluster analysis produced six types of LHDs with
differing core function patterns. By matching efforts to improve core function
practice to LHD type, more efficient use of capacity building resources may
result.
PMID- 10183163
TI - The view from under the ledge: a local health department perspective on the MCH
essential public health service framework.
PMID- 10183164
TI - Use of the MCH functions framework as a tool for strengthening public health
practice.
PMID- 10183165
TI - Key elements for developing a successful MCH program focused on quality and
health status outcome indicators.
PMID- 10183166
TI - Important directions in public health surveillance and community-based research
in maternal and child health: a CDC perspective.
PMID- 10183167
TI - Comparisons: The basis for measuring public health performance.
PMID- 10183168
TI - Sharing responsibility for the public's health: a new perspective from the
Institute of Medicine.
AB - The health of a community is a shared responsibility of many entities. Within
this context, specific entities should identify, and be held accountable for, the
actions they can take to contribute toward the community's health. Governmental
public health agencies, especially at the state and local levels, can take the
lead in getting public and private community organizations to advance the health
of the community, and should play a leadership role by developing partnerships
with managed care organizations and community-based organizations.
PMID- 10183169
TI - AIDS surveillance: knowledge, attitudes, and practices of health care
professionals in Washington State.
AB - Health professionals in Washington State were surveyed in 1993 to assess acquired
immunodeficiency syndrome (AIDS) reporting knowledge, attitudes, and practices.
Seventy-five percent responded. Two thirds of previous reporters were informed
about the 1993 AIDS case definition and reporting requirements, but 32 percent
had neglected to report. Forty-eight percent were concerned about confidentiality
of reported cases. Half favored human immunodeficiency virus reporting and 21
percent opposed it. In order to promote complete and timely AIDS reporting,
current and future reporters need ongoing education on reporting requirements and
methods. The importance of AIDS surveillance data for community planning as well
as assurance of protection of confidentiality should be emphasized.
PMID- 10183170
TI - Setting standards for the Wisconsin HIV Counseling and Testing Program: an
application of threshold analysis.
AB - Human immunodeficiency virus (HIV) counseling and testing (CT) services are an
important component of any comprehensive HIV prevention program. Because
resources are limited and must be used wisely, it is important to determine if
the expenditures on CT services are sufficiently effective that they might be
considered cost-saving or cost-effective to society. The policy analysis
technique of "threshold analysis" was employed to determine how many HIV
infections the publicly funded Wisconsin CT program would have to prevent in
order to be considered cost-saving or cost-effective. Depending on the
calculation method used, the threshold for the minimum number of HIV infections
that must be averted ranges between approximately 1 and 18 (for the year 1994).
Although the exact number of HIV infections prevented by these services in
Wisconsin in unknown, the best estimate of this number is well over the required
threshold. Hence, HIV CT services in the state of Wisconsin appear to be cost
saving to society.
PMID- 10183171
TI - Trends in infant mortality in Connecticut, 1981-1992.
AB - Assessing infant mortality rates (IMRs) is important in public health planning.
However, single year fluctuations in IMRs often receive attention without
consideration of long-term trends. Trends in IMR over 12 years in Connecticut
were examined using linked birth and death files. Overall, there was an
exponential decline in IMR from 12.2/1,000 live births in 1981 to 7.3/1,000 live
births in 1992. However, differential declines in IMRs resulted in an increased
relative risk of infant death over time for infants of Black women compared with
infants of White women. IMRs were also higher for infants of Black, teenaged, and
less educated mothers. Targeted local maternal and child health programs are
needed if IMRs are to continue to decline for all sections of the population in
Connecticut.
PMID- 10183172
TI - Statewide coverage of very low birth-weight infants and young teenage mothers in
North Carolina's Child Service Coordination Program.
AB - North Carolina's statewide, interagency Child Service Coordination Program (CSCP)
serves children under five years of age with or at-risk for diverse health and
developmental conditions. Preliminary assessment of the CSCP linked existing
datasets to examine program coverage for two target populations: mothers < 15
year of age and infants < 1,500 g. The expectation that statewide program
coverage would be higher for both risk groups in 1993 than in 1991 was true for
mothers less than 15 years of age but not for infants < 1,500 g. This efficient
method of evaluation can direct program outreach to the areas where it is most
needed and provide a focus for more detailed program evaluation.
PMID- 10183173
TI - Immunization registry: problems and prospects for boosting vaccine coverage of
children.
AB - Case studies are presented on three organizational models for immunization
registries in local communities: agency-based, facility-based, and population
based systems. The strengths and limitations of the respective approaches are
highlighted. Each model faces three similar challenges: generating "real-time"
information on the status of children who fall behind on their immunizations,
assuring confidentiality of registrants and medical information, and maintaining
operations amidst adverse social conditions that are at the root of
underimmunization of children. With sufficient resources and cooperation among
many private and public interests, registries have considerable potential to
increase vaccination coverage among our population.
PMID- 10183174
TI - St. Louis Integrated Immunization Information System.
AB - The immunization rate for St. Louis, Missouri, children age two and younger is
only 49 percent, below the statewide rate of 64 percent and far below the
estimated national rate of 75 percent. In response to this crisis, the St. Louis
Integrated Immunization Information System (SLIIIS) was designed to establish an
on-line immunization information system, identify barriers to immunization among
health care providers and the client population, and implement methods for
removing these barriers. Available to both public and private health care
providers, SLIIIS uses a population-based approach to monitoring and improving
immunization levels in the Eastern Missouri Region. SLIIIS was initiated by a
partnership of an academic center with community agencies and institutions.
Review of initial development efforts and system design may be valuable to others
involved in creating regionally integrated information systems.
PMID- 10183175
TI - Injury prevention and control.
PMID- 10183176
TI - Federal support for development of injury prevention and control programs at
state and local levels--a call to action.
PMID- 10183177
TI - The chrysalis of state health department injury control programs.
PMID- 10183178
TI - Alaska's statewide trauma registry: a useful surveillance tool for injury
prevention planning and evaluation.
AB - The state of Alaska is unique because it is one of a small number of states with
a surveillance system that collects trauma information from every hospital in the
state. The Alaska Trauma Registry (ATR) collects up to 144 data elements for
every injured patient. Information from the ATR is useful as an injury
surveillance tool for federal, state, and local governments and other agencies
and organizations when planning and evaluating injury prevention programs.
Combining trauma registry data with Bureau of Vital Statistics cause of death
data provides complete, statewide, population-based data on all injuries serious
enough to result in death or hospitalization.
PMID- 10183179
TI - Injury prevention capacity building in New York State: federal support played a
significant role.
AB - Federal funds contributed substantively to an expanded infrastructure for injury
prevention (IP) in New York State at all levels. Indicators of capacity building
included increased recognition of injury as a priority public health (PH) issue,
enhanced interagency collaboration around IP, stimulation of planning around
preventive strategies, training of more PH practitioners in IP, improved use of
injury surveillance data, increased local IP projects, development of a PH
approach to violence prevention, and broadened statutory authority for IP.
Practical "lessons learned" offer generalizable insights. Specific funding
strategies to support IP infrastructure and to link research with application can
maximize the effectiveness of future injury capacity building efforts.
PMID- 10183180
TI - Developing injury prevention capacity in New York City: the role of a local
health department in fostering collaborations.
AB - Injuries have long been a leading cause of mortality in urban areas such as New
York City. While efforts to address injuries were undertaken by the New York City
Department of Health (NYCDOH) starting in the 1940s, it was not until the
department received a Capacity Building Grant from the Centers for Disease
Control and Prevention (CDC) in 1989 that a more comprehensive program could be
developed. The NYCDOH launched several collaborative projects with a variety of
organizations and institutions. These efforts indicate that through
collaborations, local health departments can increase their effectiveness and
better promote their approach to injury prevention.
PMID- 10183182
TI - Critical factors in building local capacity to prevent and control injury: North
Carolina's experience.
AB - In fiscal years 1991-1992, a state injury control program awarded $258,000 to 33
local health departments for 50 community-based injury prevention projects. To
determine whether this program helped build the capacity of local health
departments to prevent injury, project reports were reviewed and project
directors were surveyed. For four of six factors developed to assess capacity
building, success was demonstrated for all local projects to some degree.
However, continued support is necessary to assure that the local health
departments can sustain this capacity and continue to develop proficiency in data
monitoring and evaluation.
PMID- 10183181
TI - Reinventing injury prevention in California: a model for reinventing local public
health programs.
AB - The evolution of state injury control programs, like the evolution of public
health itself, involves many jurisdictions and disciplines outside the health
domain and requires the cooperation and coordination of many sectors. Perhaps
most important is that it requires involvement by the states to assure success.
In California, the federal investment of less than $2 million in capacity
building spread over five years has produced more than $8 million in injury
control programming in the subsequent four years.
PMID- 10183183
TI - Family Violence Councils: the Missouri model.
AB - The burden for dealing with family violence and its related problems is steadily
being shifted toward local communities. Together, the Office of Injury Control in
the Missouri Department of Health and National Center for Violence Prevention
developed a comprehensive, multidisciplinary approach to help local communities
address family violence--the Family Violence Council. The council provides a
coordinated structure within the community for protocol and service development
and resource sharing. Some of the lessons learned include the importance of
moving beyond family violence as a "women's issue," grooming local leadership,
and fostering early success by setting achievable goals.
PMID- 10183184
TI - Missouri's Take a Seat, Please! and program evaluation.
AB - In Missouri, injuries from motor vehicle crashes are the leading cause of death
to children aged one to four. In 1984, the state legislature enacted child
passenger safety legislation, but by 1992, compliance with the law was still
disappointingly low. The Missouri Department of Health implemented a program
called Take a Seat, Please! in which concerned citizens reported motorists who
transported children under age four in a way not compliant with the state law.
Two years later, a telephone survey and a pre- and postobservation study at child
care centers did not show that the intervention had any effect. The program was
discontinued in September 1995.
PMID- 10183185
TI - Collaborative assessment: exploring parental injury prevention strategies through
bicycle helmet use.
AB - While multiple studies have investigated bicycle helmet use, qualitative studies
investigating parental strategies to promote their children's safety are rare.
Thirty-four parents were interviewed to explore their injury prevention
strategies. Findings suggest that the developmental stage of the child, the
child's gender, and rural versus urban residence are all related to strategies
parents use and their success in promoting bicycle safety. Peer pressure was the
major deterrent, and negative "parent pressure" was also identified as
problematic. Themes emerged that may support future injury prevention efforts
with children, parents, and their communities and provide agencies information
not previously captured quantitatively.
PMID- 10183186
TI - The accuracy of acute hepatitis B reporting in Hawaii.
AB - The objective of this study was to estimate the true incidence of acute cases of
hepatitis B (HB) in Hawaii in 1993 and thus determine the sensitivity of
reporting to the Hawaii Department of Health (HDOH). The study found that the
relatively low HB incidence rate of 1.6 per 100,000 reported in Hawaii in 1992 is
probably, at least in part, due to underreporting by laboratories and to
reporting requirements that are inadequate for accurate classification of acute
cases.
PMID- 10183187
TI - A lipid trial tracking system.
AB - A computerized tracking system was developed for the monitoring of recruitment
and participant follow-up in the Worcester Area Trial for Counseling in
Hyperlipidemia (WATCH). In this study, over 8,000 subjects were screened, from
which 1,278 were recruited over a two-year period. Subjects were randomized into
three conditions (one is control, the other two with interventions) and followed
for one year. Patient lipid profiles, dietary intakes, and psychosocial data were
collected at baseline and after one year. The tracking system developed proved
essential to the efficient management of WATCH and can be adapted for other
research and nonresearch purposes.
PMID- 10183188
TI - Missouri's emergency department E-code data reporting: a new level of data
resource for injury prevention and control.
AB - This article describes the results of the first statewide external cause of
injury (E-code) reporting system that includes emergency department (ED) visits.
The results indicate that for every injury-related death, there are 20
hospitalizations and 174 ED visits. Although firearms and motor vehicle crashes
were the leading causes of injury-related deaths, falls and motor vehicle crashes
were the leading causes of ED visits. An analysis of injuries in one metropolitan
statistical area in the state demonstrates similarities and differences from the
statewide results. The statewide reporting of cause of injury information in ED
visits provides valuable information for injury control efforts.
PMID- 10183189
TI - Critical relationships of managed care organizations and public health agencies.
PMID- 10183190
TI - Enlisting managed care organizations to participate in community health
improvement.
PMID- 10183191
TI - Managed care and public health.
AB - Both public health and managed care organizations share an interest in ensuring
the health status of a defined population. We explore the existing and potential
relationships between managed care organizations and public health in several
major public health areas, specifically clinical preventive services, prevention
oriented social and political policies, and core public health functions. The
latter include health information, health education, personal health services
provision, work force and research, community partnerships, and evaluation of
health care. We believe there is much potential to improve the population's
health through the collaboration of these two sectors of the health care system.
PMID- 10183192
TI - Survey results on behavioral health promotion in managed primary health care.
AB - Casual observation suggests that many managed health care providers support
health promotion and preventive care, including efforts addressing such
behavioral health objectives as reduced alcohol use during pregnancy, prevention
of family violence, and improved parenting. Respondents from roughly 40 percent
of 200 health maintenance organizations (HMOs) selected for a 1995-1996 survey
reported some type of health promotion activities with potential behavioral
health impact. These 80 HMOs were found to be divided among eight distinct models
of interaction between behavioral health promotion and managed primary health
care.
PMID- 10183193
TI - The role of local health units in a managed care environment: a case study of New
York City.
AB - With the growth of managed care, local health units (LHUs) and managed care
organizations (MCOs) across the country are forging new relationships in an
effort to serve the interests of both entities. Through collaboration, LHUs and
MCOs can maximize resources, expand health promotion efforts, and benefit from
each party's respective expertise. This study draws on the experiences of the New
York City Department of Health and other local health units to identify seven
basic models for interaction with MCOs and to present suggested steps and
strategies for LHUs to develop successful collaborations with MCOs.
PMID- 10183194
TI - Roles and opportunities for local health departments in managed care markets.
AB - Managed care organizations (MCOs) are increasing their share of many local
markets and are increasingly providing services to newly insured populations and
Medicaid eligibles. Local health departments (LHDs) in these markets must
determine what strategies they wish to pursue in this new health care
environment. Possible roles are identified (from public health services only to a
full range of services). LHDs are encouraged to use their strategic advantages to
contract with MCOs to serve geographic, socioeconomic, and cultural populations
that differ from those that MCOs are accustomed to serve. Accreditation
guidelines of the National Committee for Quality Assurance are summarized and
their relationship to LHD activities discussed.
PMID- 10183195
TI - The view from the horizon: strategic partnerships of public health, academic
medical centers, and managed care.
AB - The organization and operation of public health departments must change if they
are to participate in the evolving health system. Strategic partnerships with
academic medicine, academic medical centers, and managed care organizations offer
an opportunity to establish and sustain these new roles. A rationale for
collaboration and description of the assets each organization contributes to the
partnership is described. The experience of the authors in developing such
strategic partnerships and other examples from across the country is presented.
PMID- 10183196
TI - Private sector health care organizations and essential public health services:
potential effects on the practice of local public health.
AB - This article focuses on the activities of eight private health care organizations
undertaking public health and prevention activities. Few activities were
motivated by or integrated into the business or operating strategy of the
organizations and poor integration with the business strategy puts the long-term
future of these activities in jeopardy. The lack of integrated activity can be
attributed to: slow pace of managed care implementation; low penetrance of full
risk capitated reimbursement; and fragmented, competitive health care markets.
Purchaser pressure, quality assurance requirements, community benefit standards,
and government mandates are among the levers available to encourage such
activities by the private sector.
PMID- 10183197
TI - Implications of managed care in a publicly funded health care delivery system.
AB - In the light of federal cuts in the Medicaid budget, the Medicaid-funded health
delivery system is under severe cost pressures, especially in publicly funded
institutions. In the private health insurance industry, managed care innovations
have successfully restrained costs. For publicly funded institutions to remain
viable, managed care contracts must be implemented for the Medicaid system as
well. Managed care holds promise for reducing costs as well as reducing many of
the current barriers to quality health care for the indigent.
PMID- 10183198
TI - Medicaid managed care and STD prevention: opportunities and risks.
AB - The shift from fee-for-service reimbursement to Medicaid managed care is intended
to expand access to the uninsured and simultaneously control costs. Specific
attention must be paid to sexually transmitted disease (STD) prevention because
the Medicaid population and STD at-risk groups overlap in their demographic
descriptions. Costly, long-term sequelae can be avoided by early treatment of
many STDs. Specific agreements between Medicaid and public health agencies may
encourage managed care organizations to improve service in the areas that have
traditionally been the territory of public health.
PMID- 10183199
TI - The cost-effectiveness of HIV prevention from a managed care perspective.
AB - This article offers a preliminary examination of the intersection of managed
care, HIV prevention, and economic considerations. After introducing a basic
framework for evaluating the cost-effectiveness of HIV prevention interventions,
it reviews the cost-effectiveness literature. The article also examines how the
concerns of managed care organizations impact the cost-effectiveness of HIV
prevention efforts, including counseling and HIV antibody testing, small group
cognitive-behavioral interventions, and community-level interventions. The
article closes with a discussion of non-financial incentives for promoting HIV
prevention within a managed care framework.
PMID- 10183200
TI - Medicaid managed care and childhood immunization delivery.
AB - Childhood immunization rates can be used as a barometer of the quality of care
delivered to children. Medicaid managed care has the potential to improve
childhood immunization delivery by implementing population-based medicine in
primary care. Studies of immunization rates under Medicaid managed care have
found mixed results; in some settings immunization rates were higher for children
covered by Medicaid managed care than for children covered by fee-for-service
Medicaid, but in other settings immunization rates were similar for children in
the two types of Medicaid programs. In most studies, overall rates were well
below national guidelines for all populations enrolled in Medicaid.
PMID- 10183201
TI - Childhood lead poisoning and managed care.
AB - Childhood lead poisoning is a problem that disproportionately affects
impoverished children. Many aspects of affected children's lives may be involved
in the prevention and treatment of this disease. Changes in child health services
are occurring in the context of fundamental changes of virtually all human
services. Managed care changes may alter the sites where children get primary
care services, the content of that care, and linkages of medical services to
public health, nutrition support, housing, mental health, education, and social
services. This article discusses the opportunities and the dangers that managed
care changes may pose to the prevention and treatment of childhood lead
poisoning.
PMID- 10183202
TI - Medicaid managed care partnerships to improve perinatal outcomes.
AB - New York State's Prenatal Care Assistance Program, and enhanced care program
based on public health principles, is in the process of being transformed into
Medicaid managed care. The program described in this article, namely, a Medicaid
managed care health maintenance organization and its interaction with one
hospital's care of women, especially pregnant women, serves to illustrate how
traditional public health values and managed care principles may be linked. This
linkage is a starting point to developing a community's involvement in its own
health, although it is too early from our experience to note a lasting effect on
improved pregnancy outcomes.
PMID- 10183203
TI - The provision of enabling services to higher-risk pregnant women and children in
Medicaid managed care.
AB - As managed care organizations become the major payer model for the higher-need,
higher-risk population of Aid to Families with Dependent Children women and
children, they would benefit from looking at lessons learned during the past
decade as policy makers and providers struggled to identify less costly, but
effective strategies to reduce morbidity and mortality associated with poor birth
outcomes. This article discusses the experience of one community in providing
enabling services, the opportunity for new partnerships, measuring the outcomes,
and the financing of enabling services in a managed care model.
PMID- 10183204
TI - Oversight of managed care for behavioral health services.
AB - Contract specifications for behavioral health services can be used to ensure that
services are accessible, efficient, and effective. Staff-per-population ratios
and service utilization rates derived from the health services research
literature, are proposed as a practical set of performance indicators.
Structural, process, and outcome indicators are included. Examples include
therapist full-time equivalents per 1000 cases (structural), number of crisis
calls per 1000 enrollees (process), and number of emergency department visits per
1000 (outcome). The need for occasional clinical audits and further research in
other areas is discussed.
PMID- 10183205
TI - Reflections on the 1994 elections.
PMID- 10183206
TI - Adult day care: a fragmented system of policy and funding streams.
PMID- 10183207
TI - The search for effective alternatives to conservatorship: lessons from a daily
money management diversion study.
AB - This article explores outcomes of daily money management (DMM) services for older
persons. It is based on research that examined the ability of DMM to provide an
alternative to court-appointed conservatorship that is less restrictive. Results
indicate that although the DMM programs studied did not divert older persons from
conservatorship, they appeared to offer several important advantages. These
included helping older persons secure benefits and services, enhancing their
financial security, and reducing financial exploitation.
PMID- 10183208
TI - Inheritance law in an aging society.
AB - An exploratory analysis of states' inheritance law changes between 1961 and 1990
was conducted in order to discern major trends and their implications for older
families. Results suggested that states were modifying their laws in ways similar
to suggestions of the law community's Uniform Probate Code, with about one third
of the states adopting the Code itself. Consequently, inheritance law has become
less traditional and paternalistic and more like "facilitative law," that is,
flexible, accommodating, and supportive of family autonomy and decisionmaking
authority. These changes and new laws that simplify procedures, protect the
dependent and vulnerable, treat marital property more like community property,
recognize variant family forms, and enable extrafamilial bequests, may serve to
minimize family disruption, conserve resources, and allow families to tailor
property divisions and procedures to particular needs and wishes. An impact study
is proposed for disclosing the actual effects on inheritance law reforms. Also,
while trends observed in this study were fairly evident, states' adoption of new
laws was uneven and selective, inviting continuing trend analyses and further
research into the reasons for interstate variation.
PMID- 10183209
TI - Age discrimination and early retirement policies: a comparison of labor market
regulation in Canada and the United States.
AB - As public policy issues, mandatory retirement and age discrimination are
approached differently in Canada and the United States. The legal frameworks,
enforcement procedures, and judicial decisions are distinct in the two
jurisdictions. The United States, unlike Canada, has specific legislation to
protect the rights of older workers, and has a centralized enforcement system.
The differences between the two countries are accounted for by the greater
emphasis on individual rights in the United States and on communitarianism in
Canada. The different policy choices of each society highlight the tensions
inherent in North American labor markets. The United States seems to be in a
better position to shift toward a labor-management policy which encourages older
workers to remain in the workforce.
PMID- 10183210
TI - Medicare managed care: to ration or to rationalize.
PMID- 10183211
TI - Assessing the implications of the 1994 elections for aging policy.
PMID- 10183212
TI - Aging policy in the Clinton Administration.
PMID- 10183213
TI - Can regulation improve long-term care insurance? Lessons from the Medigap
experience.
AB - This article uses recent experiences from the Medigap market to draw conclusions
about the advisability of alternative methods of regulating the market for long
term care insurance. The analysis is based in part on interviews of state
insurance regulators, insurance companies, and interest-group representatives.
The authors conclude that some regulation of the market is appropriate, but that
the structure and extent of regulation found in the Medigap market would likely
be inappropriate for the long-term care insurance market at this time.
PMID- 10183214
TI - Bringing together housing and aging services: the experiences of area agencies on
aging.
AB - Aging organizations generally do not consider housing issues as an important
priority. Research suggests that lack of knowledge may be a significant barrier
that prevents their involvement in housing-related activities. This article
reports on a study that examined the extent and level of AAAs' involvement in
housing-related activities with particular attention to instances of cooperation
and collaboration between AAAs and housing agencies. It employed a national
survey of Area Agencies on Aging (AAAs). Further, since the lack of knowledge
about housing is a barrier to involvement, the study examined the role of a
housing specialist in motivating higher levels of activity. Though there is no
single overall indicator of activities to do with housing, the results indicate a
range of activities pursued by AAAs. The presence of a housing specialist within
the AAA generally served as a catalyst, motivating higher levels of this kind of
activity. The importance of housing as a component of a comprehensive long-term
care continuum is also discussed.
PMID- 10183215
TI - Senior centers and services for the frail elderly.
AB - This article reviews and synthesizes the research on senior center programming
and utilization relating to one important group of elders--the physically and
mentally frail. It examines the thesis that senior centers do play an important
role in providing programs for this population, especially given the resources
available to them, and can be considered as part of the long-term care continuum.
The article also identifies a number of barriers that limit how much most centers
do in serving significant numbers of frail older persons.
PMID- 10183216
TI - Injustice in family care of the Chinese elderly in Hong Kong.
AB - With increasing longevity, family care of the Chinese elderly in Hong Kong is
evolving as a "caring trap" for female caregivers, especially unmarried
daughters. Despite this, as Hong Kong is still a patriarchal Chinese society,
most of the major decisions affecting the destiny of frail elders are made by
sons or other male members of the family. The unequal gender roles, obligations,
and division of caregiving responsibilities within the Chinese family and their
effects on the caring relationship are discussed. Implications of this injustice
based on gender regarding family care of the elderly and the possibility of its
elimination are examined.
PMID- 10183217
TI - Health care reform, long-term care, and the future of an aging society.
PMID- 10183218
TI - From nursing homes to home care: introduction.
PMID- 10183219
TI - Financing reform for long-term care: strategies for public and private long-term
care insurance.
AB - The way the nation provides for the financing and delivery of long-term care is
badly in need of reform. The principal options for change are private insurance,
altering Medicaid, and public long-term care insurance. This article uses the
Brookings-ICF Long-Term Care Financing Model to evaluate each of these options in
terms of affordability, distribution of benefits, and ability to reduce
catastrophic out-of-pocket costs. So long as private insurance is aimed at the
elderly, its market penetration and ability to finance long-term care will remain
severely limited. Affordability is a major problem. Selling to younger persons
could solve the affordability problem, but marketing is extremely difficult.
Liberalizing Medicaid could help solve the problems of long-term care, but there
is little public support for means-tested programs. Finally, universalistic
public insurance programs do well in meeting the goals of long-term care reform,
but all social insurance programs are expensive and seem politically infeasible
in the current political environment.
PMID- 10183220
TI - Designing home care benefits: the range of options and experience.
AB - This article presents a framework identifying important home care benefit design
decisions and reviews existing designs that have been adopted in practice. Four
basic designs were identified, based on a review of 55 home care benefits drawn
from public programs in the United States and foreign countries, and from private
long-term care insurance policies in the United States. Three of these designs
service entitlements, managed-service benefits, and cash disability allowances-
have each been adopted by public programs in the United States and abroad, and by
private insurance policies in the United States. A fourth design--individualized
cash benefits--has been adopted in only one experimental program. The designs
observed in practice are remarkably varied, providing evidence that many
alternative designs are feasible. Experimentation, particularly with cash
disability allowances, is needed to determine the relative costs and benefits of
various designs.
PMID- 10183221
TI - Home care: moving forward with continuous quality improvement.
AB - The utility of examining the effectiveness of home care is illustrated by
selected examples and applications. The growth rate of home care over the past
decade, questions regarding the possibly substantial differences between the
quality of home care in rural and urban America, and empirical evidence that
suggests inferior quality of home care for health maintenance organization
patients support the need for measuring and monitoring outcomes of home care. The
conclusions of a research program targeted at developing a system of outcome
measures for home care, and the resulting national demonstration program to
implement and refine that system, are summarized.
PMID- 10183222
TI - Long-term care policy and the American family.
AB - This article examines current and proposed long-term care policies and the social
values of American families by looking at the influence of policy on family
behavior. The analysis asks two questions. First, have our policies in recent
years supported or undermined family values regarding the care of older members?
Second, are our existing family values compatible with home and community-based
long-term care reform proposals? Aaron, Mann, and Taylor's (1994) model for
policy and changing values provides direction throughout. Findings based on
behavior as a proxy for values suggest that current policies influence family
values, and in turn, family values influence policies. Future policy is discussed
in light of changed values, American family structure, dysfunctional families,
individualism and collectivism, and gender neutrality and justice.
PMID- 10183223
TI - Changes in health, mortality, and disability and their impact on long-term care
needs.
AB - The need for long-term care is driven both by the growth of the elderly
population and changes in the age relations of morbidity, disability, and
mortality. Data show these relations changed in the U.S. elderly population from
1982 to 1989. Chronic disability prevalence declined between the 1982 and 1989
U.S. National Long Term Care Surveys. Among those impaired, many persons using
personal assistance to meet their needs shifted to the use of assisted housing
and special equipment. The relation of these trends to other changes--such as the
increasing educational level of the elderly population--is examined to estimate
how future changes in disability and morbidity may affect the demand for long
term care. Disabilities at specific times as well as their transition rates were
examined to determine how long individuals need long-term care. The analyses
suggest that, while the amount of long-term care services needed will increase
rapidly, the types and amounts of services used by the U.S. elderly population
will undergo significant change.
PMID- 10183224
TI - Ways of thinking about the long-term care of the baby-boom cohorts.
AB - In examining various ways of thinking about the development of long-term care
policy for the baby-boom cohorts, this article discusses the importance of basing
long-term care policy discussions on a recognition of social and economic trends,
as well as on the informal exchanges of care that occur over life and the
diversity within the baby-boom cohorts. The implications of two ways of thinking
about challenges posed by the aging of baby boomers--the generational
equity/crisis perspective and the generational investment/gradual adjustment
perspective are also discussed. It is suggested that the generational equity
perspective is consonant with proposals to expand private savings for long-term
care contingencies and private long-term insurance and, secondarily, with
proposals to expand means-testing for benefits. The second perspective is more
consistent with proposals to create new universal services through a traditional
social insurance approach, or through a block grant such as the one discussed in
the context of the Clinton health care reform plan.
PMID- 10183225
TI - Home and community-based care: recent accomplishments and new challenges.
AB - This article traces the development of home and community-based care to its
current place in the worlds of health and social policy. An argument is developed
to the effect that such services have by now gained both heightened policy
legitimacy and organizational capacity. Building on these contentions, the
article goes on to suggest that such services should continue to gain a more
prominent place within long-term care policy, and that long-term care issue
deserve a more central place within social insurance policy more generally. The
article concludes by suggesting that demonstrations of policy efficacy such as
those that are taking place in home and community services might help to at least
modestly offset the frontal assault which is currently taking place across the
range of American social policy.
PMID- 10183226
TI - Informal care vs. formal services: changes in patterns of care over time.
AB - Longitudinal data from a representative sample of community-residing older
persons were used to document changes in patterns and costs of care, both
informal and formal. It was found that use of formal services was usually in
conjunction with, and secondary to, informal care. Limited availability of
informal care as well as increased disability raised the odds of using services.
Substitution of formal services for informal care was limited and usually
temporary. Total costs of community care, including living expenses, were
generally less than the cost of nursing home care.
PMID- 10183227
TI - Race and gender differences in the distribution of home and community-based
services in Florida.
AB - This article examines the distribution of home and community-based services
(HCBS) under Florida's Medicaid waiver program. Controlling for personal and
community characteristics, it was found that gender and race significantly affect
the access of the disabled adult population to HCBS services, with women and
nonwhites significantly more likely to be receiving HCBS services. At the county
level, the likelihood of one's being in the waiver program is contingent on the
racial composition and level of segregation of the county. People residing in
counties with substantial proportions of nonwhites are less likely to receive
HCBS services--whatever their race. However, the higher the rate of racial
segregation in the county, the higher the probability that the Medicaid disabled
adult population will receive HCBS services. The Medicaid waiver program allows
older, disabled black women to remain in their home neighborhoods rather than
having to move to predominantly white areas where nursing homes are concentrated.
Thus, the HCBS program not only provides them with a form of care that is
preferred by most older people but also resolves market problems stemming from
the lack of nursing homes in segregated areas by taking advantage of support
systems in black households.
PMID- 10183228
TI - Public policy and the 104th Congress.
PMID- 10183229
TI - The end of an era.
PMID- 10183230
TI - Demographic and socioeconomic aspects of elderly migration in the 1980s.
AB - The availability of data from the Current Population Survey for each year makes
it possible to monitor the migration behavior of the population on a year-to-year
basis and facilitates efforts to detect changes in long-standing patterns of
behavior. The data used in this article come from the published reports
summarizing the results of the March administration of the Current Population
Survey over a decade, and, in general, deal with the movement of persons during
the 12-month interval immediately preceding the survey. Trends and changes in
some of the principal aspects of migration behavior among the elderly are
reviewed and summarized, focusing on the demographic, social, geographic, and
economic dimensions. Also considered are differences in migration behavior along
these dimensions from a temporal perspective as well as in comparison to the
migration behavior of the younger population. When possible, the article provides
insight on behavioral differences among the various age categories within the
older population, differentiating between the youngest and oldest components of
the group and recognizing the striking differences between the youngest and
oldest members of the older population in nearly all aspects of the migration
process.
PMID- 10183231
TI - Utilizing volunteer research assistants in epidemiologic studies.
AB - Utilizing volunteers in research-assistant roles can provide a new model for
extending research dollars in epidemiologic studies of the elderly. This is
increasingly important with a rapidly growing older population suffering from an
increasing prevalence of disability, disease, and the related medical costs.
During a two-year cross-sectional study of factors that predict health aging
conducted by the Buck Center for Research in Aging in Marin County, California,
82 volunteers were recruited and trained to fill roles often held by paid
research assistants. The key activities of telephone screening, interviewing,
coding, and data entry were successfully completed by trained volunteers
following standards and within a time frame comparable to similar studies.
Volunteer research assistants contributed approximately 13,600 hours that
resulted in a savings in personnel costs of over $100,000. Many of the people
recruited and trained as volunteer research assistants were healthy older adults
and retired workers. The project utilized their transferable skills and talents
in an interesting and productive capacity.
PMID- 10183232
TI - A study of utilization and satisfaction: implications for cultural concepts and
design in aging services.
AB - This article describes the utilization and satisfaction patterns of Native
Hawaiian elders with the Ke Ola Pono No Na Kupuna ("Good Health and Living for
the Elderly") project funded under Title VI-B of the Older Americans Act. Data
were collected through a self-administered questionnaire. Its unique, one of a
kind, culturally specific program, which includes traditional Native Hawaiian
meals, has a number of implications for policy considerations in designing aging
programs that can serve ethnic minority aged more effectively. Changes in current
federal policy that would enable federally mandated aspects of programs to
provide for greater flexibility in providing culturally relevant programs and
services for ethnic minorities would help to surmount some of the current
problems and barriers to service delivery and utilization by ethnic minority
groups. Allowing for greater involvement of ethnic minorities in program design
will help to assure culturally relevant and appropriate activities and services
and may increase the likelihood of success due to a sense of personal ownership
and self-responsibility on the part of those involved.
PMID- 10183233
TI - Stipended volunteers: key to reducing turnover?
PMID- 10183234
TI - Political elites and regulatory bureaucrats: a case study concerning age
discrimination.
AB - In 1988, the U.S. Senate Special Committee on Aging held a hearing on
effectiveness of the Equal Employment Opportunity Commission (EEOC) with regard
to age discrimination cases. The Hearing reported that approximately 7,500 age
based claims had run the statute of limitations. The article analyzes the
ideological context of regulation, first, by explaining the purpose, procedures,
and effectiveness of the EEOC in enforcing the Age Discrimination in Employment
Act. Secondly, the article analyzes the 1988 Senate Hearing, including background
issues and immediate outcomes. Thirdly, it discusses what has happened since 1988
from the perspectives of political elites, regulatory bureaucrats, and interest
group members.
PMID- 10183235
TI - Introduction: Japan's aging society.
PMID- 10183236
TI - Between policy and practice: Japan's Silver Human Resource Centers as viewed from
the inside.
AB - The Silver Human Resource Centers (SHRC) were first established in 1980 to
address the economic and psychological needs of Japan's growing numbers of senior
citizens. The Centers, through which people are introduced to jobs in their
locales and from which they receive remuneration for services performed, are by
now well established throughout Japan. This article examines the gap between SHRC
members' evaluations of the Centers and the Center guidelines, as stated in their
published literature and in interviews with program administrators. The analysis
is fourfold: (1) it explores the members' reasons for participating in the
program; (2) it discusses their assessments of it; (3) it examines gender and
social class differences in program planning and participation; and (4) it
analyzes the Ministry of Labor's plan for new directions for the Centers.
Although new policy directions do address many members' concerns, they do not
attempt to question or change the status quo of the gendered division of labor in
Japanese society.
PMID- 10183237
TI - The health status of elderly people and the new direction of health services.
AB - The projected increase of people in Japan aged 75 years and older in the years to
come implies the increase of the disabled elderly. Thus, the core of societal
preparation for the aging of the population is generally considered to be the
expansion of services for the disabled elderly. However, gerontological studies
on the health status of the elderly conducted in Japan show that the prevalence
of disability is quite low and even decreasing. Relative to the services for the
disabled elderly, preventive services for the healthy elderly have long been
overlooked. In 1994, the Metropolitan Tokyo Government organized a task force to
develop a new health education program as the preventive health service for the
healthy urban elderly. A preliminary plan outlining the health education program-
consisting of propagation with a booklet, on-the-job training of practitioners,
and development of new curricula and teaching materials--was proposed by the
authors for discussion within the task force. Although the inquiry has just begun
and the plan is still nascent, it seems adequate to fit the needs for preventive
health services in the near future.
PMID- 10183238
TI - Implementing public policies and services in rural Japan: issues and problems.
AB - While the sharply increased services for the elderly in the revised Gold Plan-
announced in 1994--are noteworthy, implementation of the revised Plan is expected
to present numerous issues and problems, particularly in the rural areas of
Japan, because of unique circumstances such as depopulation and the presence of a
disproportionately large number of elderly; geographical and physical isolation;
a conservative and tradition-bound political climate; and conservative attitudes
of the elderly. This article examines the current state of policy implementation,
identifying issues and problems that are being encountered in the rural areas of
Japan. Such issues as economic and family life, health care, and service delivery
for the elderly are examined.
PMID- 10183239
TI - Expansion of formalized in-home services for Japan's aged.
AB - This article analyzes the social and political forces in Japan that led to the
creation of the Gold Plan, a comprehensive national plan for formalized in-home
services for the aged. The political strategies of the Gold Plan are examined
from the following perspectives: (1) shifts from institutional to in-home
services, (2) decentralization of in-home services policy, and (3) needs for
expanding the number of in-home service workers. New nonprofit organizations
called Resident-Participation Types (RPTs) are identified, which are self-help
organizations to augment the delivery of in-home services to the aged. The
current status of these new models for the aged are examined, using data from two
different surveys conducted by the Japanese National Council of Social Welfare in
1992 and 1993. Finally, future issues regarding RTPs and in-home services for the
aged and some policy recommendations are discussed.
PMID- 10183240
TI - Possibilities for change toward universal design: Japanese housing policy for
seniors at the crossroads.
AB - Japanese government policies for seniors have long assumed that informal care by
their families exists for them. The rapid aging of Japan is eroding the basis for
this assumption. It is now necessary to include barrier-free design concepts in
the basic requirements for dwellings to be used by everyone, not just seniors, to
support independent living. Essential requirements in proposed guidelines are
already in effect in the design and construction of publicly operated rental
housing. But at this time, only the schemes of the Housing Loan Corporation of
Japan for additional loans are being used, in cases where some design
requirements for senior users are being met. The Housing Loan Corporation's loan
system has long been seen as a policy on the part of government to boost the
economy, particularly during recessions, but assistance for construction of
higher quality dwellings has been lacking. This article discusses the basic
philosophy of design guidelines and practical ideas to be considered in dwelling
design and the merit of model dwellings constructed by housing manufacturers in
Japan. It also discusses potential strategies to implement the basic ideas of
design guidelines. It then proposes some possible methods to realize life-span
dwellings, or dwellings designed for everybody.
PMID- 10183241
TI - From transfer to social service: a new emphasis on social policies for the aged
in Japan.
AB - The Gold Plan, the central government's attempt to build a nationwide network of
care service provision for the aged, seems partly because of its patchwork
character and partly because of its stress on the low-cost strategy to be running
into two problems: (1) It is adding new institutional ambiguities and functional
confusion to the old fragmentation, instead of producing a well-integrated
system; and (2) the response to the central policy varies much across the
municipalities (its carriers) so a disparity among them in the level of service
provided is emerging. A "public care service insurance" scheme, in the planning
stages since April 1994, will offer a solution to the first problem. However, it
will leave the second problem unsolved and may introduce a market factor into the
field of social service. As it is, the service provision itself is overwhelmingly
entrusted to private organizations.
PMID- 10183242
TI - Japan's financing system for health care of the elderly.
AB - The multiplicity of Japan's health insurance system fails to achieve equality
among the different insurance groups of the sharing of the financial burden. This
"horizontal" inequality is effectively offset by a unique redistribution
mechanism established in 1982. However, there is no reserve fund so that savings
can be accumulated for the greater financial need in the future. This will
inevitably lead to a heavier financial burden for the future working generation
or more utilization of the personal assets of the elderly. How to achieve
"vertical" or intergenerational equality in financing the cost of health care for
the elderly is the biggest social policy challenge for Japan.
PMID- 10183243
TI - Paying for the health and social care of the elderly.
AB - The aging population of Japan is causing serious concern among social
policymakers. The most urgent issue is to find a way to pay for the health and
social care of the frail elderly. After universal coverage of pension and health
insurance was achieved, but just before the economic growth rate was considerably
slowed, in part, because of the oil crisis, the Japanese government more than
doubled pension benefits and made medical care for the elderly free. Since the
early 1980s, the government has tried hard to cut and control these benefits,
only with moderate success. With a consumption tax rate of only 5%, rather than
the proposed 7%, the government is now considering establishing a new health and
social care insurance scheme for the elderly to finance the increasing cost of
their care.
PMID- 10183244
TI - An overview of work, retirement, and pensions in Japan.
AB - Work to retirement in Japan is a sequential transition for the most part, and
Japan permits mandatory retirement by firms at age 60. But many older people work
beyond the age of 60, many more than in other industrialized countries. A number
of hypotheses are examined, having to do with pensions, health, opportunity,
interest in working, cultural attitudes (including the concept of ikigai), and
public policy initiatives (such as employment policy and the Silver Human
Resource Centers). Japan's cultural attitudes and existing policies appear to
have set Japan on a unique course in considering the aging of its population. To
what extent should other nations emulate Japan?
PMID- 10183245
TI - The challenge of an aging work force: keeping older workers employed and
employable.
AB - This article reviews labor-force trends and older-worker employment policies in
Japan and the United States. Both countries have aging work forces, but Japan's
labor force is and for some time has been older than that of the United States.
Japan's Ministry of Labor began addressing older-worker issues over 30 years ago
and in the ensuing years has promulgated numerous initiatives to extend working
life. Mandatory retirement, however, remains both legal and common in Japan, yet
labor-force participation rates are higher for older persons in that country than
in the United States, where mandatory retirement is illegal. Japan's older-worker
programs and policies clearly seem to have an impact on labor-force rates,
although those rates are dropping among the elderly in Japan as well as in the
United States. The transferability of these programs and policies to the United
States is discussed.
PMID- 10183246
TI - Policies for a smoother transition from work to retirement.
AB - Japan has maintained a relatively high labor-force participation rate among older
people. Although the rate had declined steadily until the mid-1980s, the trend
has since reversed and the participation rate is expected to rise in the future.
In contrast, the labor-force participation of older people has sharply declined
in the United States and European countries, especially since the 1970s. This
article explores why Japan's experience differs markedly from other advanced
countries. Improved pensions have a strong influence toward early retirement,
even in Japan. However, other factors such as a low replacement ratio, improved
health, and several loopholes in the income test of the pension systems push up
the participation rate of older people. The government also encourages active
labor-force participation of senior citizens by introducing reformed partial
working pensions and wage subsidies for workers in their second and third
careers.
PMID- 10183247
TI - Fostering a rational debate on social insurance.
PMID- 10183248
TI - Employment discrimination against older workers: an experimental study of hiring
practices.
AB - Pairs of resumes, one for a 57-year-old and the other for a 32-year-old, were
mailed to 775 large firms and employment agencies across the United States.
Although the resumes presented equal qualifications, the older job seeker
received a less favorable employer response 26.5% of times when a position
appeared to be vacant. Vigorous enforcement of equal opportunity laws as well as
initiatives to change employer attitudes are appropriate responses to such
discrimination. The technique of employment testing, demonstrated in this
research, can be useful in both efforts.
PMID- 10183249
TI - A global overview of major or unique libraries, clearinghouses, and bibliographic
databases in social gerontology.
AB - Eighty-six major and/or unique information resources in social gerontology,
mostly in the form of libraries, clearinghouses and other hybrid resources, and
bibliogrphic databases were identified through an international survey. They are
practically all located in the more developed countries, and the large majority
are in the United States. A growing number are available in electronic format,
facilitating direct end-user access. Significant information gaps continue to
exist and access to the data resources of the northern hemisphere remains a major
problem for developing nations.
PMID- 10183250
TI - Urban/rural elderly health status differences: the dichotomy reexamined.
AB - Health policy research analyzes urban/rural differences as a simple dichotomy.
Research characterizes the rural elderly as having a higher incidence of
sickness, dysfunction, disability, restricted mobility, and acute and chronic
conditions than their urban counterparts. However, population density as a
dichotomy may obscure urban, rural, or urban/rural differences. Interviews
measuring health status were conducted with a representative sample of 2,300
elderly people in six Northeastern Ohio counties constituting an urban/rural
continuum. On medical condition, use of medical aids, and symptoms, health status
improved significantly when moving from rural to urban, but correlations were
small. Using dichotomies, urban elderly reported fewer medical conditions and
symptoms than rural elderly, but four other health-status variables revealed no
significant association and results differed depending on how dichotomies were
defined. When individual communities were compared few urban/rural patterns
emerged. Controlling for demographics did not change interpretations. Findings
question blanket assertions about urban/rural health-status differences. Medical
resources may be misallocated. Rather than assuming poor health status among the
rural elderly, researchers must verify differences through community-based
research.
PMID- 10183251
TI - Ability, disability, and the oldest old.
AB - A measure of range of ability is used to profile the 85-years-old-and-older
(oldest old) population, including the highly disabled institutional population.
This new measure uses two new questions available in the 1990 Decennial Census
concerning a self-care limitation and a mobility limitation as well as the usual
question concerning a work limitation. In addition to examining the extent of
disability among the oldest old, the article examines the extent of care
potentially available in the household as well as the economic characteristics of
this age group. It is also profiled in terms of relevant personal
characteristics, including age, gender, marital status, race, ethnicity, rural
residence, education, and employment. A key question addressed is the need for
help or care among the oldest old and how various long-term care proposals would
meet such needs. A careful analysis of this unique and growing population is
necessary to both allay fears of the cost of care or help as well as to dispel
stereotypes of this age group as frail and dependent, and in need of
institutional care.
PMID- 10183252
TI - Defining the challenges of providing long-term care: the case of the nursing home
industry's response to the AIDS epidemic.
AB - Acquired Immune Deficiency Syndrome (AIDS) is now viewed as a chronic disease
requiring long-term management. As a result, more persons with AIDS (PWAs) are
seeking long-term care in facilities that have primarily served the elderly. In
some regions, however, the nursing home market into which PWAs may introduce new
demand is a market already characterized by excess demand. In light of this,
competition for limited long-term care resources may develop between the frail
elderly and PWAs. The nursing home industry has raised many issues regarding the
feasibility of admitting AIDS patients as residents, but little is known about
how important these issues are in deciding admissions policy. How the industry
perceives and resolves the concerns it has regarding delivery of care to PWAs can
affect the overall long-term care system and thus affect the traditional users
the frail elderly. Knowing the concerns and preferences of the industry may help
guide and anticipate future changes in the system. In this pilot study, a random
sample of 250 nursing home administrators in the five highest AIDS-incidence
areas in the United States was surveyed to determine (1) the industry's concerns
and issues regarding AIDS care, (2) data regarding requests for admission by PWAs
to nursing homes, and (3) data concerning the industry's preferred way of
delivering AIDS care. Important admissions policy issues cited by the respondents
included the ability to meet special care needs, costs of care, and inadequate
reimbursement. The majority also believed the most appropriate methods of
providing care were special care units for AIDS within nursing homes or dedicated
HIV/AIDS nursing facilities.
PMID- 10183253
TI - The extent and nature of alcohol-related problems in public senior housing.
AB - To examine both the extent and nature of alcohol-related problems in senior
housing and how management responds to these problems, 100 local housing
authorities (LHAs) in Connecticut with responsibility for senior housing were
surveyed. The response rate was 90%. Results indicated variability among LHAs
regarding their experiences with alcohol misuse among residents. It was evident
in the numbers of residents abusing alcohol, the procedures for addressing
problems when they occur, and LHAs' assessment of the extent and seriousness of
problems. Few LHAs had either staff training regarding alcohol abuse or policies
to address alcohol-related problems. Conclusions concerning whether alcohol
related problems were widespread in public senior housing were related to the
size of the LHA. Housing specialists, public policymakers, and educators should
assist management personnel in developing policies and procedures regarding
misuse of alcohol. In addition, resources should be directed to educate housing
authority staff about detection of the problem and strategies for intervention.
PMID- 10183254
TI - Setting priorities in aging populations: formal service use among Mexican
American female elders.
AB - This study establishes empirical patterns of formal service use by a sample of
483 elderly Mexican American women, and identifies the predictors of formal
service utilization. Results indicated two patterns of service use-in the home
and at senior centers. Regression analysis demonstrated that the best predictors
of who used formal in-home services were those with functional impairment in
Instrumental Activities of Daily Living (IADLs) and those with the least amount
of assistance with IADLs provided by family members. Living alone and attending
group social events were the best predictors of the use of senior center
services. Anticipated changes in the Mexican American population portend a
growing need for both in-home and senior center services. These findings can be
used to establish policy and programming priorities for this neglected
population. If resources are to be effectively targeted to frail elders, in-home
services should receive priority, and the provision of in-home services should be
modified to include additional programs that facilitate care of the elderly by
the family.
PMID- 10183255
TI - Ask older women: are the elderly better off?
PMID- 10183256
TI - Discrimination of older workers in Germany: obstacles and options for the
integration into employment.
AB - The employment prospects of older workers in Germany are widely endangered
because of age discrimination. The main indicator concerning recruitment is that
from the age of 45 on the difficulties in finding a new job rise extraordinarily
and, accordingly, the duration of unemployment rises. Concerning further
training, there is a lack of participation by older workers in vocational
training and, additionally, they face numerous risks in the deterioration of
their skills. Given the long-term implications of the aging labor force,
employers must adapt their approaches to recruiting and training older workers to
prevent a further loss of skills and know-how. A comprehensive strategy for
integrating older workers and overcoming age barriers in employment is required.
To promote recruitment, job-placement programs should be linked more closely to
companies and public programs should be targeted to older unemployed workers. To
promote further training of older workers, the workplace needs to create a
learning environment, introduce a greater variety of tasks, and develop training
schemes.
PMID- 10183257
TI - Evaluation of media advocacy efforts within a community trial to reduce alcohol
involved injury. Preliminary newspaper results.
AB - This article examines coverage of alcohol-related topics in local newspapers as
applied to a conceptual model of media advocacy being tested in a five-component
community trial to reduce alcohol-involved injuries. Based on a literature review
of determinants of exposure of newspaper articles, it uses a composite measure
that takes into account the likelihood that given articles will be read. This
measure is evaluated in terms of the timing of media advocacy training, technical
consultation, and resulting media advocacy efforts. Three hypotheses find
support. First, postintervention levels of coverage across experimental
communities appear generally higher than similar preintervention coverage.
Second, although postintervention local and county coverage appears higher across
experimental communities, no equivalent effect is present across comparison
communities. Third, increases in local and county coverage in experimental
communities were not matched by increases in state and national coverage in these
communities.
PMID- 10183258
TI - Panel accretion and external validity in adolescent substance use research.
AB - This study investigates the relationship of panel accretion to panel attrition
and examines its impact on threats to external validity in adolescent substance
use research. Panel accretion involves the addition of new participants to a
panel design after initial baseline data has been obtained. Accretion occurs in
longitudinal studies in which data is routinely gathered on all participants, as
is often the case in prevention or epidemiological research on adolescent
substance use. Accretion, attrition, and panel findings for three, 2-year panel
samples in grades 7 through 9 are examined. The results indicate that accretion
and attrition samples have an isomorphic relationship to one another on a range
of dependent measures when drawn from the same population. The results are
discussed in terms of their implications for adolescent substance use research,
the examination of validity threats due to panel bias, and understanding the
ecological validity of research findings.
PMID- 10183259
TI - Implications of increased infectivity in early-stage HIV infection. Application
of a Bernoulli-process model of HIV transmission.
AB - Recent reports suggest that the infectivity of sexually transmitted HIV (i.e.,
the probability of transmission on a single sexual contact) may be up to 1,000
times greater during the first few months of infection than during the long
asymptomatic period that precedes the development of AIDS. Assuming the validity
of this estimate, a simple Bernoulli-process model of HIV transmission indicates
that, in some cases, the expected number of secondary infections is greater for
the brief period of primary infection than for the much longer asymptomatic
phase. The implications of these findings for current HIV/AIDS prevention
practices are analyzed with particular attention to the role of condom use in
preventing HIV transmission.
PMID- 10183260
TI - Toward a reliable measure of breast self-examination. Attitudes and performance
barriers.
AB - Breast self-examination (BSE) attitude scales are typically administered as part
of face-to-face interviews or telephone surveys. The purpose of this study is to
test the reliability (i.e., internal consistency) of a newly developed BSE scale
that can be self-administered. The scale is made up of 24 items, each rated on a
5-point Likert-type scale. The scale items cover such issues as perceived
seriousness and susceptibility to breast cancer, perceived effectiveness of
breast self-examination, and personal barriers. Preliminary results were
encouraging. Results of an exploratory factor analysis suggest that six factors
may underlie this scale (common variance = 53%). Areas of item and scale
improvements and implications for the use of this scale in health evaluation
research are discussed.
PMID- 10183261
TI - Predictors of misreporting cigarette smoking initiation among adolescents.
AB - This study examines the prevalence of invalid reports of cigarette smoking
initiation among adolescents (i.e., reporting cigarette smoking at one time point
and denying ever trying cigarettes at a subsequent time point) and the
association of misreports with scores on other problem-prone variables.
Misreports did not vary as a function of item complexity and did not reflect
careless responding. In the seventh grade, misreporters' scores on the problem
prone variables were higher than those of nonsmokers and lower than those of
smokers. In contrast, when measured in the eighth grade, misreporters' scores did
not differ from those of nonsmokers. Misreporters did show a greater decrease in
intentions to smoke, alcohol use, and number of friends who smoke compared to
nonsmokers and consistent smokers. Explanations for these findings are discussed.
PMID- 10183262
TI - Where's the best medicine? The hospital rating game.
AB - On July 18, 1994, U.S. News and World Report published its annual ranking of
America's best hospitals. The rankings were based on a model developed by the
National Opinion Research Center (NORC). National rankings are a type of program
evaluation that deserve careful scrutiny with regard to their methods. While
problems with measurement validity are discussed, the principle concern here was
the model used to compile a final ranking of hospitals. The News-NORC model is
typical of ranking schemes that usually reduce higher levels of measurement to
lower ones in order to compute final scores. Such simple tabulation techniques,
however, distort the ratios between the scores and bias the results. A type of
percentaging, using part/whole percentages (P/W%), was used to show the
differences between hospital rankings when data are kept at higher levels of
measurement, such as interval or ratio levels. Percentaging methods produce more
valid results when comparatively evaluating programs whether the goal is to
produce national rankings or some other outcome.
PMID- 10183263
TI - Two-unit reliability analysis of questionnaires used in a regulatory system.
AB - An interjudge reliability test was conducted to evaluate the questionnaires used
in the surveillance of residential care institutions. Because the reliability
test was carried out as part of the routine surveillance program and not as part
of a controlled experiment, it was subject to deviations from the optimal
reliability test model. However, this nonpure design provided an opportunity to
not only examine the reliability of the items in the surveillance tool, but also
to gain a better understanding of the use of a reliability test in an "imperfect"
field setting. Two different surveyor teams administered the 257 questions on the
questionnaires to a representative sample of 32 institutions on two separate
occasions. In order to explain the variance in the reliability scores, a
multivariate analysis was conducted for two units of analysis: the surveillance
questions and the institutions. Based on the results of the reliability test,
changes were introduced to improve the questionnaires and their administration.
PMID- 10183264
TI - Statewide substance abuse prevention planning.
AB - The State of Rhode Island contracted with the authors to prepare a statewide,
comprehensive substance abuse prevention plan. The literature review revealed a
lack of research on statewide planning for prevention services. To obtain data
for Rhode Island's plan, the authors conducted a family of studies including
synthetic estimation, key informant interviews, a telephone survey of agency
directors, program budget analysis, construction of a statistical index for
estimating the optimal geographic allocation of prevention dollars, and a review
of General Laws regarding tobacco, alcohol, and other drugs. Their
recommendations include the increased funding and coordination of prevention
services, allocating services according to need rather than population size,
greater use of social policy as a prevention tool, and a shift in primary
prevention programming from senior high to lower grades and in program emphasis
from information-education to psychosocial programs.
PMID- 10183265
TI - Matching anonymous pre-posttests using subject-generated information.
AB - Sensitive research issues call for anonymous questionnaires. This makes
accurately matching pretests with posttests difficult or impossible. Various
subject-generated coding schemes have been developed, but their accuracy has been
unknown. This anonymous study, with 745 students, used subject-generated coding
to match pretests with posttests. The matching was verified for accuracy with the
use of a collateral, anonymous, sticker identification system. The coding system
was able to accurately match 75.2% of all the pretest-posttest pairs. An
additional 22.1% of the pairs were left unmatched and only 2.7% were matched
incorrectly. Subject-generated coding systems can be very effective where
confidentiality is important to protect.
PMID- 10183266
TI - Active parental consent in school-based research. An examination of ethical and
methodological issues.
AB - To date, most school-based research has used passive parental consent. However,
the Family Privacy Protection Act of 1995 aims to change these requirements. The
proposed legislation requires written parental consent if minors are to be asked
"sensitive" questions as part of any program or activity funded in whole or in
part by the federal government. This act is representative of a growing trend
toward restricting research involving minors. Whether or not this act is passed
by Congress, two lines of concern are highlighted by this legislation. The first
deals with ethical issues surrounding consent procedures. For instance, are
parental rights compromised when active consent is not mandated? A second line of
inquiry pertains to the effect of active consent procedures on response rates and
sample bias. In this article, the authors discuss ethical issues surrounding
passive and active consent procedures and then report response rates from two
projects in which active consent procedures were implemented.
PMID- 10183267
TI - Environmental equity in Superfund. Demographics of the discovery and
prioritization of abandoned toxic sites.
AB - This article presents findings of the first national tract-level analysis of the
distribution of residential characteristics, including the percentage of selected
minorities and socioeconomically disadvantaged groups, in relation to
uncontrolled toxic waste sites (i.e., CERCLIS and NPL sites). In contrast to
prevailing notions, the authors find that uncontrolled toxic waste sites are not
disproportionately located in minority neighborhoods or neighborhoods of
socioeconomically disadvantaged residents. However, multivariate analyses of site
distribution and a hazard regression analysis of the site prioritization process
suggest that communities with a higher percentage of Black residents are less
likely to receive NPL (National Priorities List) designation, delaying potential
remediation. Biases in the prioritization process are, however, substantively
small.
PMID- 10183268
TI - Undetermined manner of death. A comparison with unintentional injury, suicide,
and homicide death.
AB - Injury deaths can be grouped into four general categories: accident, homicide,
suicide, and undetermined. The present study investigates the use of the
"undetermined" category. External cause of death, as well as demographic and
other variables, were abstracted from death certificates of the 386,936
Californians who died of an injury between 1969 and 1991. Differences among the
four manner-of-death groups were examined, and characteristics of the decedent
and the injury event were used to predict a classification of undetermined.
Coroners classified 1.9% of the deaths as undetermined in manner. Deaths of
women, Blacks, Asians, and Native Americans; the very young and the middle aged;
or those involving poisoning or submersion were most likely to be classified as
undetermined. Acknowledging that individual coroner judgment may not be free of
bias, these findings can help provide a better estimate of the frequency and the
epidemiologic features of injury deaths that are assigned to the category of
undetermined.
PMID- 10183269
TI - Coroner-reviewed infant and toddler deaths. Many "undetermineds" resemble
homicides.
AB - Although homicide is a leading cause of death of infants and toddlers, there is
some suspicion that an unknown number of additional deaths are unrecognized
homicides. The authors used California mortality data from 1969 to 1991 to
examine 12,246 injury deaths that occurred before age 5. Characteristics of the
dead child, injury event, and postmortem were compared for accidents, homicides,
and undetermined deaths. A logistic model was developed to differentiate
homicides from accidental deaths and then was used to predict whether
undetermined deaths were likely to be homicides or accidents. Unlike accidental
deaths, undetermineds and homicides had similar distribution patterns of age,
race, sex, and place of injury. The predictive model indicates that 43.8% of the
undetermined injury deaths were similar to homicides on several characteristics.
True rates of homicide for infants and toddlers may, unfortunately, be nearly one
fifth and one tenth higher, respectively, if the undetermined deaths that
resemble homicides are taken into account.
PMID- 10183270
TI - Implementation and process evaluation of a student "school-as-community" group. A
component of a school-based drug abuse prevention program.
AB - Little documentation exists regarding the functioning of formalized adolescent
groups as drug abuse prevention agents. Two studies are described that were
conducted at high schools whose students are at high risk for drug abuse. Twenty
one schools were randomly assigned to one of three conditions: (a) standard care,
(b) classroom drug abuse education only, or (c) classroom plus school-as
community. Results of the first study indicated that the school-as-community
component--which involved weekly meetings and periodic events at seven schools-
was implemented as planned, drug abused focused, and perceived as productive in
discouraging drug abuse. In the second study, staff in the classroom plus school
as-community condition self-reported involvement in the greatest number of
community activities across the school year, compared with staff from the other
two conditions. These two studies support the feasibility of formalized groups of
high-risk youth to promote drug-free events.
PMID- 10183271
TI - Evaluating efforts to reduce community-level problems through structural rather
than individual change. A multicomponent community trial to prevent alcohol
involved problems.
PMID- 10183272
TI - Evaluation design for a community prevention trial. An environmental approach to
reduce alcohol-involved trauma.
AB - The Community Prevention Trial was 5-year effort to reduce alcohol-involved
injuries and death through a comprehensive program of community awareness and
policy activities. The three experimental communities were of approximately
100,000 population each (one in Northern California, one in Southern California,
and one in South Carolina). Matched comparison communities were used for each
experimental community. This article describes the evaluation approach used in a
program that sought to change environmental factors not a specific population or
target group. This approach demanded unique evaluation approaches for determining
overall community aggregate effects, that is, distal outcomes, as well as changes
in key mediating variables, that is, process effects. The problem of trending and
lagged effects of community prevention programs are discussed.
PMID- 10183273
TI - Community mobilization, organizing, and media advocacy. A discussion of
methodological issues.
AB - Community Mobilization refers to those activities that prepare communities to
accept, receive, and support prevention interventions designed to reduce alcohol
involved trauma. Media advocacy refers to the strategic use of media by those
seeking to advance a social or public policy initiative. Within the Community
Prevention Trial, both of these activities were critical elements. This article
presents the evaluation design for community mobilization and media advocacy
implemented for the project. Here the authors argue for the need to include both
structured and unstructured community monitoring instruments, coding of local
alcohol-related news coverage, and surveying community members about the exposure
to alcohol-related problems, and support for project interventions. This article
also presents an audience segmentation analysis and discusses the implications of
this analysis for media advocacy efforts.
PMID- 10183275
TI - Analysis approaches to community evaluation.
AB - Analysis approaches to the evaluation of community interventions must be
sensitive to a wide variety of analytic contaminants that may bias the
statistical assessment of changes in outcome measures. These contaminants include
model misspecifications related to failures to control for community-specific
time trends, temporal autocorrelated errors in equations, spatial autocorrelated
errors among geographic units, and other failures of unit independence otherwise
indexed by estimated intraclass correlations. Although an enormous amount of
progress has been made toward the solution of many of these analytic problems
over the past years, the contemporary evaluator of community interventions is
left with a number of unenviable design and analysis choices; choices that
inevitably force an assessment of the relative threats of different sources of
error to the internal and external validity of the evaluation. This article
describes the choices made for the evaluation of the Community Trial Project
outcome data.
PMID- 10183274
TI - Documenting community-level outcomes. Lessons from drinking and driving.
AB - Alcohol-related crashes cluster on Friday and Saturday evenings. One objective of
this study was to contrast the demographic characteristics of operators who drive
at these times with those who do not, through the comparison of data from two of
the most widely used methods for gathering information on drinking and driving:
Random Digit Dialing Telephone Surveys and Roadside Voluntary Breath Test
Surveys. Roadside surveys set up at locations where alcohol-related crashes occur
provide a better sample of those drivers most at risk of crash involvement.
Telephone surveys, because they do not generally measure the exposure of drivers
both in the location of driving and the number of miles driven, are less suited
to identifying the drivers at risk. However, they highlight the large number of
individuals who drive during high-risk times but avoid high-risk locations.
PMID- 10183276
TI - Monitoring youth behavior in response to structural changes. Alternative
approaches for measuring adolescent drinking.
AB - Random digit dial (RDD) telephone and self-administered school-based surveys of
drinking and drinking and driving were compared for adolescents from two Northern
California communities. The RDD and school-based surveys resulted in very
different samples. The telephone sample contained a greater proportion of
European Americans and a smaller proportion of Asian Americans and "other"
ethnicities. Respondents to the telephone sample also tended to be older and of
higher socioeconomic status (SES). The telephone survey captured very few school
dropouts. Moreover, it resulted in lower self-reports of drinking and drinking
and driving. Survey mode appeared to influence respondents equally, regardless of
their gender, age, ethnicity, or SES.
PMID- 10183277
TI - Evaluating specific community structural changes. Examples from the assessment of
responsible beverage service.
AB - Responsible Beverage Service (RBS) refers to the idea that bars and restaurants
may be able to have a significant impact on the levels of deaths and injuries
associated with alcohol consumption including, but not limited to alcohol
impaired driving. After a brief background on RBS as a prevention strategy, the
authors review the different measures, protocols, and designs that have been
employed in evaluations of responsible service programs with attention paid to
the strengths and limitations accompanying each choice. This article concludes by
describing the Prevention Research Center's Community Trials Project design as it
relates to evaluating its RBS component, and some of the unique considerations
that influenced the measures and protocols employed. In so doing, the authors
discover how the larger project serves as an interesting case study in action
research.
PMID- 10183278
TI - Summing up. Recommendations and experiences for evaluation of community-level
prevention programs.
AB - This article provides recommendations and observations about evaluation of a
locally based prevention project to reduce problems at a total community or
aggregate level. The shift from targeting specific individuals or subpopulations
to the overall structure and environment of a community is most demanding.
Evaluation tools and analysis techniques have lagged behind program development
because community-level interventions are not linked to a specific target group
who can be separately studied. Thus assumptions about using random assignment
and/or comparison communities as means to control for confounding variables are
weakened when the unit of analysis is the community itself and dependent measures
are subject to trending and the effects of history.
PMID- 10183279
TI - Measuring quality in mental health services.
AB - This article introduces the special issue on measuring quality of care. The
overall purpose of this issue is to encourage an increased presence of evaluators
in quality-of-care research. The sections of this special issue are devoted to
conceptual issues concerning quality and the future of quality measurement. They
include a description of current governmental and private efforts in measuring
quality, a brief report on quality measurement efforts in Great Britain, and four
quality-of-care research reports.
PMID- 10183281
TI - Following the bouncing ball of quality.
AB - Quality of health care is important to all individuals. As an area of research
and evaluation, quality is of considerable interest to a wide variety of
professionals. Increasingly, independent assessments of the quality care have
become important components of purchasing for employers and consumers. This
article offers a personal perspective on the emerging trends in quality and
identifies several related implications, with behavioral health examples, as well
as opportunities for interested evaluation researchers.
PMID- 10183280
TI - Validating quality indicators. Quality as relationship between structure,
process, and outcome.
AB - Theory and research have not kept pace with the growing interest in evaluating
quality of mental health care, resulting in the use of unvalidated quality
indicators. A framework for validating quality indicators is offered by which
quality is viewed as the relationship between service structures, processes, and
outcomes. Adoption of this framework will facilitate the measurement of quality
using valid indicators and should be useful to agencies in their continuous
quality improvement efforts. Valid information about the quality of mental health
care services will help purchasers and consumers make more informed health care
decisions.
PMID- 10183282
TI - Mental health quality measurement in the Department of Defense. A developing
system.
AB - In response to the need for high-quality mental health care for its beneficiaries
at appropriate cost to the government, the Office of the Assistant Secretary of
Defense (Health Affairs) has developed a quality and utilization management
program that requires contracted organizations to manage care through appropriate
means. The system provides for oversight of utilization management contractors by
a national quality monitoring contractor and a proposed utilization management
criteria set based on an analysis of criteria sets currently used in government
and industry. This article describes the program at its current level of
development.
PMID- 10183283
TI - Managed behavioral health care premises, accountable systems of care, and AMBHA'S
perms. American Managed Behavioral Healthcare Association.
AB - This article discusses the concepts and approaches underlying managed behavioral
health care and the need to assess quality of care. The author describes the
Performance Measures for Managed Behavioral Healthcare Programs (PERMS) developed
by the American Managed Behavioral Healthcare Association (AMBHA), which is
offered as a first step toward enhanced quality of care assessment in managed
behavioral health care.
PMID- 10183284
TI - Joint commission evaluation of behavioral health care organizations.
AB - The joint Commission on Accreditation of Healthcare Organizations has accredited
behavioral health care organizations since 1957. Accredited behavioral health
care organizations include organizations providing services to persons with
psychiatric disorders, substance abuse disorders, or developmental
disabilities/mental retardation; or, provide social services to other related
populations. In the late 1980s, the Joint Commission initiated the redesign of
accreditation to include performance measurement. Performance measurement
initiatives include the IMSystem, Requests for Indicators, National Library of
Healthcare Indicators, and a national Council on Performance Measurement. These
initiatives are steps toward the integration of performance measurement data into
the accreditation process.
PMID- 10183285
TI - The MHSIP mental health report card. A consumer-oriented approach to monitoring
the quality of mental health plans. Mental Health Statistics Improvement Program.
AB - Health care report cards have been endorsed as a mechanism for efficiently
comparing key quantifiable aspects of performance across a range of health
systems or plans. There are challenges in determining what to measure; how to
gather and analyze data; and how to report, interpret, and use findings. Mental
health has received little attention, and a consumer perspective is typically not
included. The proposed MHSIP mental health report card (MMHRC) addresses these
concerns. General issues for report cards are discussed, and the MMHRC is
described in terms of content, data sources and quality, and analysis and
reporting.
PMID- 10183286
TI - In the eye of the storm. Promoting quality initiatives for behavioral health
care.
AB - The restructuring of how behavioral health care services are financed, managed,
and delivered has controlled costs but raised concerns about quality. The need
and opportunity has never been stronger for professionals and organizations from
previously disparate segments of the field to closely collaborate on broad-based
quality initiatives. This article reviews the collaborative initiatives
established by one organization that are affecting all segments of the field
through research projects, publications to disseminate information, and
conferences to promote discussion. Implications, new directions, and
opportunities for evaluation researchers are proposed.
PMID- 10183287
TI - NAMI'S managed care report card. National Alliance for the Mentally Ill.
AB - This article reports on the National Alliance for the Mentally Ill (NAMI)
national report card to examine quality of care under managed care. The national
report card will provide a summary of state policies underpinning the move of
managed care into the public mental health system, and directly probe consumer
and family member perceptions and experiences of managed care and the policies
and practices of managed care organizations.
PMID- 10183288
TI - How consumers/survivors are evaluating the quality of psychiatric care.
AB - In the past decade, mental health consumers have increasingly become involved in
evaluating the quality of psychiatric care and applying sophisticated data
strategies to affect system reform. Through multistakeholder partnerships, they
have identified outcome indicators, collaborated in the development of a mental
health report card, and designed and conducted consumer self report surveys on
satisfaction and needs and preferences for housing and supports. The formation of
multistakeholder assessment teams; the definition of the consumer perspective
through focus groups and concept-mapping pilots; and research on coercion,
personhood, recovery, and empowerment are key activities of consumers/survivors
in the field of evaluation.
PMID- 10183289
TI - Assessing quality in mental health care. The United Kingdom experience.
AB - Quality assessment in mental health services is undergoing change in the United
Kingdom following the introduction of market reforms. Traditionally, service
quality was monitored by professional practitioners with reference to user
satisfaction. This became formalized, and the two main forms of quality assurance
currently used are outlined. However, the government is concerned that this may
be inadequate for the monitoring of quality standards, specified in contracts
between service purchasers and providers, and that existing systems provide an
insufficient indication of service outcome. As a consequence, the government
financed the development of a new set of health outcome scales. The importance of
these scales are discussed.
PMID- 10183290
TI - Automated pharmacy databases and behavioral health care quality assurance.
AB - Randomized, double-blind, placebo-controlled trials suggest that medications can
be efficacious in several psychiatric disorders. The effectiveness of medications
as they are used in practice remains to be seen. Automated pharmacy data give
evaluation researchers tools to examine the quality of care for people using
psychotropic medications. Reasonably convincing data indicates that automated
pharmacy records are valid measures of medication consumption. Evaluation
research is needed in areas such as standard setting, risk adjustment, and the
linking of pharmacy data to outcome measures.
PMID- 10183291
TI - Addressing issues of face validity in the application of a clinical guideline.
AB - In 1995, a statewide project to improve the practice of electroconvulsive therapy
(ECT) in the Medicare population was started in Louisiana. A retrospective
baseline study found high concurrent utilization of lithium and benzodiazepines,
medications considered detrimental to ECT by the second American Psychiatric
Association Task Force on ECT. Resistance to a clinical guideline because of lack
of face validity by clinicians was used as an opportunity to involve clinicians
in using data to evaluate their clinical practices. Results of the first two
quarters of the project demonstrated that the strategy was successful.
PMID- 10183292
TI - Exploring the link between service quality and outcomes. Parents' assessments of
family support programs.
AB - Relationships among consumer-generated quality factors, satisfaction, and outcome
measures were examined for family support services provided by Michigan's public
mental health system. Parents focused on structural and procedural aspects of
program accessibility and attended less to program administration issues. Parents
who gave the services the highest quality ratings also were the most satisfied
with services, saw the services as more effective, had fewer family problems, and
rated their time and child-related resources as more adequate. Implications for
evaluation practice are discussed.
PMID- 10183293
TI - Effectiveness of care and improvement of quality of life in patients with panic
disorder.
AB - To investigate how practice guidelines or recommendations can be applied in the
assessment of quality of care, 72 subjects beginning specialty treatment for
panic disorder were enrolled. The Panic Outcomes Module assessed symptoms, health
status, and treatment at baseline and after 8 weeks. Using published guidelines,
the authors developed specific criteria to rate whether subjects' reports
reflected appropriate treatment, including antipanic medication or three or more
subsequent visits that involved antipanic behavioral therapy elements. Sixty-nine
subjects (96%) completed the Panic Outcomes Module at both baseline and follow
up. Improvement in symptoms and health status was not different between subjects
receiving appropriate and inappropriate care.
PMID- 10183294
TI - Long-term impact of Drug Abuse Resistance Education (D.A.R.E.). Results of a 6
year follow-up.
AB - The long-term effectiveness of Drug Abuse Resistance Education (D.A.R.E.) was
assessed by contrasting drug use and other D.A.R.E.-related attitudinal latent
variables among 356 twelfth-grade students who had received the program in the
6th grade with 264 others who did not receive it. A prior study of these subjects
when they were in 9th grade had shown no significant differences. A follow-up
survey in 12th grade assessed central D.A.R.E. concepts such as self-esteem,
police bonds, delay of experimentation with drugs, and various forms of drug use.
Although the authors found no relationship between prior D.A.R.E. participation
and later alcohol use, cigarette smoking, or marijuana use in 12th grade, there
was a significant relationship between earlier D.A.R.E. participation and less
use of illegal, more deviant drugs (e.g., inhalants, cocaine, LSD) in a
development sample but not in a validation sample. Findings from the two studies
suggest a possible sleeper effect for D.A.R.E. in reference to the use of harder
drugs, especially among teenage males.
PMID- 10183295
TI - The impact of drug education and prevention programs. Disparity between
impressionistic and empirical assessments.
AB - In the course of evaluating drug prevention programs for youth, we observed that
although staff perceived the programs had quite favorably affected youths'
attitudes and behavior, responses from these youths showed little significant
impact on their use or attitudes related to drugs. This article explores several
explanations for the disparity between staff impressions of the impact of these
programs and results from attempts to measure impact objectivity. The analysis
considers (a) clients' risk-level for drug use, (b) expectations as to how
programs affect client behavior and attitudes, and (c) the sensitivity of
empirical measures to ascertain changes reflecting impact of the program.
PMID- 10183296
TI - Random-effects models for analyzing clustered data from a nutrition education
intervention.
AB - When evaluating the effects of public health intervention, larger units, or
clusters, of individuals are often the unit of randomization and implementation.
Ignoring dependency in the data due to clustering can misrepresent intervention
effects. Random-effects models (REMs) may be a useful way to analyze such data.
The present study compares results of analyses of data from a nutrition
intervention program using four different methods: (a) usual multiple regression
analysis using individual subject data, (b) usual multiple regression analysis
using the classroom cluster as the unit of analysis, (c) two-level REM model with
subjects clustered within classrooms, and (d) two-level REM model with subjects
clustered within sites.
PMID- 10183297
TI - The impact of a written parental consent policy on estimates from a school-based
drug use survey.
AB - The authors examine differences between mean, variance, and correlation parameter
estimates derived from a full school-based sample and subsamples restricted by
the provision of parental consent. A total of 1,607 students at 21 continuation
high schools and 1,192 students at 3 traditional high schools completed a survey
containing variables related to sociodemographics, drug use, mental health, and
violence. The employment of a researcher-initiated home-telephone-call procedure
substantially increased the parental response rate over a student-/school
assisted consent method. The subsamples restricted by the written consent
criterion showed some small biases in estimates of sociodemographic variables but
little or no biases on measures related to mental health, drug use, or violence
measures. The augmentation of the written consent samples with verbally consented
students reduced observed biases.
PMID- 10183298
TI - The irrelevance of evidence in the development of school-based drug prevention
policy, 1986-1996.
AB - This article examines development in school-based drug prevention policy and
programming since the Anti-Drug Abuse Act of 1986. Using data from national
surveys and evaluations of school-based programs, it argues, first, that there
was really no need for a massive infusion of money into school-based drug
prevention in the late 1980s, and, second, that there was little or no evidence
to indicate that a "new generation" of effective programs, based on the so-called
social influence model, was emerging at this time. Despite the infusion of
resources into school-based prevention efforts, adolescent drug use has risen in
recent years. Moreover, evaluations continue to show that the effectiveness of
social influence programs is very much in the eye of the beholder. Fundamental
questions need to be asked of school-based drug prevention--just as they should
be asked of other key components of our current drug control policy.
PMID- 10183299
TI - 100 years of "just say no" versus "just say know". Reevaluating drug education
goals for the coming century.
AB - Through comparative socio-historical analysis of American school-based drug
education, this review critically examines past perspectives and practices and
how they shaped current programs. Among the key findings emerging from this
analysis: Contrary to the popular belief that drug education began in the 1960s,
its roots actually go back at least 115 years to the advent of compulsory
temperance instruction. Although the particular substances targeted by such
approaches have changed, the underlying approaches and dominant "no-substance
use" injunction has not. Despite the existence of "informed choice" approaches,
throughout much of this period, evaluation efforts continue to be constrained by
the limited dictates of "no-use" perspectives. A pragmatic alternative to
contemporary "Just Say No" education is offered that strives to minimize
potential harm resulting from the uninformed misuse of licit and illicit
substances. A unique evaluative strategy designed to assess the effectiveness of
this form of "informed choice" or "harm reduction" drug education is discussed.
PMID- 10183300
TI - Zero effects of drug prevention programs: issues and solutions.
PMID- 10183301
TI - An illustration of item homogeneity scaling and multilevel analysis techniques in
the evaluation of drug prevention programs.
AB - Many reports of successful school-based intervention programs can be criticized
for their choice of a unit of analysis and for the neglect of measurement errors.
This article is an illustration of how different conclusions can be reached from
different choices of units of analyses and/or of different treatment of the data.
This is done by a reanalysis of a well-reported data set. The data is thoroughly
taken apart, using different statistical techniques. The result of the analyses
shows that earlier reported effects of a normative school-based drug prevention
program were not found. The subsequent search for moderator effects of the same
program, such as a lowering effect on the relationship between the pre- and
posttest or on the relationship between respondents' use and the use of their
friends, was not successful either. It is concluded that the null hypothesis of
zero effects should be retained. More successful was a search for individual
characteristics that show significant relationships with respondents' alcohol
use. Among them was the abuse of alcohol by adults in respondents' direct social
environment and the use of friends.
PMID- 10183302
TI - Zero effects in substance abuse programs. Avoiding false positives and false
negatives in the evaluation of community-based programs.
AB - The evaluation of community-based programs poses special design and analysis
problems. The present article focuses on two major types of errors that can occur
in such evaluations: false positive--incorrectly declaring a program to be
effective--and false negatives--incorrectly declaring a program to be
ineffective. The evaluation of a national demonstration of community-based
programs to reduce substance abuse, Fighting Back, is used to illustrate several
approaches to reduce the probability of errors. Both those errors that are
affected by the design and those by analytic approaches are considered. Ways to
assess multiple outcomes and to match the complexity of the program with design
and analytic strategies are proposed. Community trials are complex interventions,
and, although they can provide very useful information, their outcomes have to be
understood in terms of the constructs they test and the contexts within which
they are carried out.
PMID- 10183303
TI - The other side of the story. Student narratives on the California Drug, Alcohol,
and Tobacco Education Programs.
AB - Within the context of a large-scale, comprehensive evaluation of the California
Drug Alcohol Tobacco Education (DATE) program, this study sought to extend
knowledge of student perceptions of prevention education using a naturalistic
approach. The constant comparative method was used to analyze 40 focus group
interviews of risk and thriving groups conducted in 11 high, middle, and
elementary school districts. This article presents three assertions generated
solely from 490 "narrative stories" found in the data set. "At-risk" and
"thriving" students at all three levels of schooling (a) use "story" to make
sense of prevention education, and (b) distinguish use from abuse. High school
students of both groups (c) believe that hearing only one side of the substance
use/abuse story and strict expulsion policies further alienate students most in
need of help. Implications for the use of story as an assessment tool are
discussed, as are implications for substance use prevention policy.
PMID- 10183304
TI - Model-based evaluation of HIV prevention interventions.
AB - The ultimate goal of HIV prevention interventions is to reduce the spread of HIV;
however, the effectiveness of these programs is seldom assessed directly.
Although direct measurement of an intervention's impact via HIV seroincidence
monitoring is usually unfeasible, mathematical models can be used to estimate the
number of infections averted by the intervention. This article describes three
model-based summary measures of sexually transmitted HIV risk and discusses their
relevance to HIV program evaluation in general economic efficiency analyses in
particular. The calculation of these measures is demonstrated with an
illustrative application to previously published data from an HIV prevention
intervention for gay men.
PMID- 10183305
TI - A differential assessment of the cumulative versus stabilizing effect of
methadone maintenance treatment.
AB - Differential response effectiveness is examined for patients during multiple
episodes of methadone maintenance (MM) treatment. Subjects were 251 narcotics
addicts who were divided into three groups based on their daily narcotics use
pattern during their first two MM treatment periods: (1) a "stabilizing group"-
showing no daily use for both periods, (2) a "cumulative group"--showing a lower
level of daily use during the second period compared to the first, and (3) a
"deteriorating group"--showing higher daily use during the second period.
Behavioral measures for various narcotics-related variables were plotted over 4
time periods (pre-MM, during first MM, between first and second episodes, and
during second MM) were compared. Results indicated several individual differences
related to patients' response to multiple episodes of MM. Clinical, research, and
policy implications are discussed.
PMID- 10183306
TI - Constructing quantitative implementation scales from categorical services data.
Examples from a multisite evaluation.
AB - Like measures of outcome, measures of implementation are most useful and
analytically powerful when measured at client-level and are quantitative.
However, high-quality, individual-level, quantitative service utilization data
can be expensive, intrusive, or otherwise impractical to obtain. Cruder data--for
example, presence versus absence of a given service--are often more feasible to
collect, as well as more likely to be available. Consequently, evaluators can
benefit by finding ways to better exploit such data at the analysis phase to
compensate for shortcomings at the collection phase. This article documents one
such instance in which this was done. Specifically, it describes how
quantitative, client-level implementation scales were derived from qualitative
(categorical) data and used to support a cross-site synthesis of implementation
and outcome analyses in a multisite evaluation. It also suggests additional
scenarios in which quantitative implementation scales might be derived form
qualitative services data.
PMID- 10183307
TI - Estimation of seroprevalence, rape, and homelessness in the United States using a
social network approach.
AB - The authors have developed and tested scale-up methods, based on a simple social
network theory, to estimate the size of hard-to-count subpopulations. The authors
asked a nationally representative sample of respondents how many people they knew
in a list of 32 subpopulations, including 29 subpopulations of known size and 3
of unknown size. Using these responses, the authors produced an effectively
unbiased maximum likelihood estimate of the number of people each respondent
knows. These estimates were then used to back-estimate the size of the three
populations of unknown size. Maximum likelihood values and 95% confidence
intervals are found for seroprevalence, 800,000 +/- 43,000; for homeless, 526,000
+/- 35,000; and for women raped in the last 12 months, 194,000 +/- 21,000. The
estimate for seroprevalence agrees strikingly with medical estimates, the
homeless estimate is well within the published estimates, and the authors'
estimate lies in the middle of the published range for rape victims.
PMID- 10183308
TI - Early childhood intervention and juvenile delinquency. An exploratory analysis of
the Chicago Child-Parent Centers.
AB - We investigated the relation between participation in the Child-Parent Center and
Expansion Program during preschool to third grade and measures of adolescent
delinquency for low-income, mostly Black youths in the Chicago Longitudinal
Study. Based on analyses of 1,262 program and comparison-group children, duration
of program participation (0 to 6 years) and extensive participation in the
program were significantly associated with lower rates of school-reported
delinquency infractions at ages 13 and 14. Extended program participation was
only marginally associated with a lower rate of delinquency infractions over ages
12 to 16. Preschool participation alone had no systematic relation with
delinquency but was marginally associated with delinquency reports at ages 15 and
16. Reductions in school-reported delinquency were due to less frequent mobility
and to postprogram parent involvement in school. Given the high cost of crime to
society, even the relatively modest effects of early childhood intervention on
delinquency suggest that such programs can provide another weapon in the war on
crime.
PMID- 10183310
TI - The MOS 36-item short form health survey. A conceptual analysis.
AB - The SF-36 is a practical and widely-tested instrument for measuring health status
and medical outcomes. This article is not a critique of the SF-36, rather, it
underscores its viability as an instrument for measuring physical and mental
health and well-being. The article is a conceptual analysis of the SF-36, from
the viewpoint of four models of health: medical, World Health Organization,
wellness, and environmental. All four models suggest that the SF-36 be expanded
to include other dimensions of health, especially mental and social. Specific
dimensions to be included are: incidents of morbidity, satisfaction with quality
of life, absence of mental disorders, social adjustment, social support, higher
states of functioning, and adjustment to the environment. The end result of the
suggested additions would be an instrument with greater conceptual meaning, for
use in medical outcomes studies or surveys of the general population.
PMID- 10183309
TI - An evaluation of the Baltimore Community Lead Education and Reduction Corps
(CLEAR Corps) program.
AB - This evaluation examines the effectiveness of the Baltimore Community Lead
Education and Reduction Corps (CLEARCorps) program in reducing lead dust levels
in low-income urban housing in Baltimore, Maryland, through minor lead-reduction
activities and tenant lead-poisoning prevention education. Lead dust data
collected before and after lead-reduction activities show statistically
significant mean declines for floors, window sills, and window wells. Limited
data using tests also show that follow-up lead dust levels collected 6 months
after the CLEARCorps intervention were significantly lower than preintervention
lead levels. Although there are many important of this analysis, the findings
suggest that in-place management may be an effective method in reducing childhood
lead poisoning in high-risk areas.
PMID- 10183311
TI - The proper use of self-report questions in effective measurement of health
outcomes.
AB - Outcomes research often relies on the use of general population survey data. The
recent efforts to employ cognitive science theory in the development of data
collection instruments has led to the establishment of new questionnaire design
research methods. Intensive cognitive techniques are used in laboratory
interviews to develop and pretest self-report survey questions with the goal of
reducing non-sampling response error. This article presents the theoretical and
applied approach used in the cognitive laboratory to study the ways people
respond to surveys, and offers guidelines for improving self-report survey
questions.
PMID- 10183312
TI - Measuring health outcomes for depression.
AB - In this article, we describe the clinical and health-related quality of life
outcome measures for depressed patients in the Medical Outcomes Study, a 4-year
longitudinal study that started in 1986. We prioritize the measures in terms of
importance, consider how they can be improved in future studies, and discuss how
they should be used in more applied evaluations, such as studies by managed care
companies and group practices. We emphasize the importance of identifying
appropriate evaluation questions and selecting study designs and patient
populations that permit meaningful answers about evaluating outcomes of care for
depression. Although the outcome measures described here may be a useful starting
point, they will need to be combined with carefully constructed measures of
process of care as well, so that links between the two can be maximized.
PMID- 10183313
TI - Assessing the effectiveness of mental health care in routine clinical practice.
Characteristics, development, and uses of patient outcomes modules.
AB - The health care delivery system faces continually increasing pressure to be
accountable for the historically unparalleled amount of resources it utilizes.
This article discusses one set of recently developed tools known as outcomes
modules that are used to assess how treatment affects outcomes in patients with a
given disorder. These tools currently are being used to inform administrative
decisions about how to improve the quality of care, and can potentially influence
decisions by patients, providers, and payers of care as well. The critical
components of outcomes modules, as well as their administration and applications
are described, using modules for psychiatric conditions as examples.
PMID- 10183314
TI - Validation of the Panic Outcomes Module.
AB - This article discusses the validation of a module designed to evaluate the
outcomes of clinical care for panic disorder. The research utilized a
longitudinal design to examine cross-sectional relationships and change over time
within and between subjects. Baseline, follow-up, and test-retest data were
collected on 73 patients. The initial field test indicates that the Panic
Outcomes Module measures outcomes and case-mix characteristics with acceptable
levels of measurement error for group data. The module's measure of change in
panic severity demonstrated encouraging agreement with the structured
interviewer's judgement of change. This module, completed in approximately 20
minutes, is short enough to incorporate into outpatient mental health settings.
We recommend that providers and administrators interested in monitoring the
outcomes of specialty care for panic disorder seek assistance from health
services researchers to use the Panic outcomes module. Further research is needed
to validate this module for use in primary care populations.
PMID- 10183315
TI - An instrument for measurement of outcomes of care for schizophrenia. Issues in
development and implementation.
AB - To advance effectiveness research in mental health, we need common, standardized,
validated instruments that can be used easily in routine practice settings. The
Schizophrenia Outcomes Module is a relatively brief, comprehensive instrument for
monitoring and assessing the outcomes of treatment for schizophrenia in clinical
care settings. The module was developed with the guidance of a
multiinstitutional, multidisciplinary expert panel; the clinical and theoretical
considerations that framed the expert panel's deliberations and determined the
module's content and characteristics are described. Initial field testing of the
instrument involved longitudinal observation of 100 individuals with
schizophrenia over a 6-month period. To our knowledge, it is the only brief and
easily administered instrument that encompasses the four major outcome domains
defined by the National Institute of Mental Health's Plan for Research on the
Severely Mentally Ill. As such, it is a promising tool for effectiveness research
in schizophrenia.
PMID- 10183316
TI - Characteristics of physicians who frequently prescribe long-acting
benzodiazepines for the elderly.
AB - Long-acting benzodiazepines (LABZs) are relatively contraindicated for elderly
patients because they increase the risk of impaired cognitive function, falls,
and hip fractures. The purpose of this study was to identify the characteristics
of physicians who frequently prescribe LABZs for elderly patients. The authors
examined the prescribing profile of 4,976 physicians who saw at least 20 elderly
Quebec medicare registrants in 1990. Physicians who frequently prescribed LABZs
for their elderly patients were more likely to have graduated before 1979, to be
general practitioners as opposed to specialists, to practice in long-term care
settings, and to have graduated from a medical school in Quebec as opposed to
other schools in Quebec, in other provinces, or in other countries. The authors
have identified several characteristics of physicians who frequently prescribed
LABZs for the elderly. Strategies to improve prescribing in this field should
target this group of physicians.
PMID- 10183317
TI - An examination of variation in long-term community tenure after psychiatric
hospitalization in eight states.
AB - The influence of seven personal and clinical characteristics on the community
tenure of discharged state hospital patients in eight states is analyzed and
discussed. Previous admission to a state hospital and a diagnosis of
schizophrenia were associated with shorter community tenure. Older patients had
longer community tenure than younger. These findings were consistent across the
states and are consistent with previous work that focused on much narrower
populations. The relationship of these risk factors to community tenure are
discussed from an individualistic perspective, a treatment oriented perspective,
and a community integrationist perspective, and implications for further research
are explored.
PMID- 10183318
TI - Chart review. A need for reappraisal.
AB - Imperfections of chart review as a data collection method are detailed, with
particular emphasis on the issue of reliability. The authors identify 125 journal
articles published between 1991 and 1992 in which the authors' conclusions were
based principally on chart review findings and were either clinical or health
care epidemiology studies, or quality assessment studies. Eight percent of
epidemiology studies and 56% of quality assessment studies presented data on
interrater reliability. Forty-four percent of epidemiology studies and 20% of
quality assessment studies did not describe the number of chart reviewers
involved. Forty-three percent of epidemiology studies and 28% of quality
assessment studies used supplementary data sources. The authors conclude that the
validity and utility of studies based on chart review would be enhanced by
attention to interrater reliability and the use of supplementary data sources.
PMID- 10183320
TI - Life in the fast lane. An evaluation of an accelerated RN-MSN program.
AB - The Pew Health Commission on professional education has recommended innovative
educational programs to promote career mobility among nurses. To assure continued
quality of nursing education in the face of innovation, the Philip Y. Hahn School
of Nursing conducted a comprehensive evaluation of its accelerated RN-MSN
program. Designed to enhance career advancement in the profession, the program
was evaluated after its fourth year of operation using the Discrepancy Evaluation
Model (DEM). Based on comparison with both relative and absolute standards, the
program shortened the time required to obtain BSN and MSN degrees and appeared to
reverse declining enrollments in the baccalaureate nursing program. Accelerated
students were as successful as other masters nursing students in specific courses
and in the program in general. Adverse program effects included declining
enrollments in some under-graduate courses and the increased complexity of
advising.
PMID- 10183319
TI - Primary care physicians and barriers to providing care to persons with HIV/AIDS.
AB - Primary care physicians play an increasingly important role in the care of
persons with HIV/AIDS due to the rising number and changing geographic
distribution of persons infected with HIV/AIDS. The study explored the
relationship between barriers to health services and the experience and
willingness of primary care physicians to care for persons with HIV/AIDS. The
study was based on a random survey of primary care physicians in South Carolina.
The results indicate that although primary care physicians' willingness to treat
persons with HIV/AIDS is significantly associated with many self-reported
barriers (i.e., financial, structural, knowledge, and attitudinal), their HIV/AID
care experience was most significantly correlated with self-reported knowledge
that overrides financial and structural barriers. The results emphasize the
importance of programs and policy initiatives aimed at enhancing the primary care
physicians' knowledge level and improving their attitudes related to HIV/AIDS.
PMID- 10183321
TI - The effect of a monetary incentive in increasing the return rate of a survey to
family physicians.
AB - The barrage of requests family physicians receive to complete mail surveys often
results in physicians who are unwilling, or unable due to time constraints, to
complete each survey they receive. Thus, to obtain an acceptable response rate,
state-of-the-art mail survey techniques must be used. This article reports the
results of the use of a modest ($1) monetary incentive to increase a survey
response rate. A random sample of 600 American Academy of Family Physicians
members were mailed a survey of firearm safety counseling; half received a $1
incentive whereas the remaining half served as a control group. The response rate
in the incentive group was 63% compared to 45% in the control group [chi 2 (1, N
= 251) = 16.0, p < .001]. Further, the use of the incentive appears to be more
cost-effective than a third follow-up (postcard reminder) mailing.
PMID- 10183322
TI - Setting standards on performance assessments of physicians' clinical skills using
contrasting groups and receiver operating characteristic curves.
AB - During recent years, the use of performance assessments for high-stakes
evaluation of physicians' clinical skills has increased. As a result,
considerable attention has been given to the identification of appropriate
procedures for setting standards on performance assessments. Several articles
have described application of the contrasting groups procedure. It appears that
the procedure is not well understood. Relatively little has been written about
the requirements for using this procedure appropriately. This article provides a
discussion of the theoretical framework for setting standards using contrasting
groups. The discussion is then extended to include the circumstance in which the
contrasting groups data are interpreted using receiver operating characteristic
curves. Examples from the research literature involving variations on the
contrasting groups method for setting standards on performance assessments of
clinical skills are discussed. The article concludes with guidelines for
evaluators interested in using the contrasting groups procedure.
PMID- 10183323
TI - What is outcomes research and what can it tell us?
AB - In 1989, Congress enacted P.L. 101-239, establishing the Agency for Health Care
Policy and Research (AHCPR). Since then, practically every specialty society has
developed practice guidelines for its practitioners, and every health care
organization has embarked on some outcomes research. Outcomes research has become
a fashion, meaning all things to all people, and runs the risk of becoming
meaningless. This article attempts to reduce the confusion by clarifying what
outcomes research is not delineating its several levels, along with the methods,
tools, and examples appropriate to each level. The contributions of outcomes
research to health care delivery innovation to date have been modest. Ultimately,
we need community health information systems, which have not only the structural
and process variables but also include the outcome results, to guide decision
making with regard to the health of entire communities and the appropriate
investment of resources to improve health.
PMID- 10183324
TI - The design of evaluations for continuous quality improvement.
AB - Many health care organizations are modeling continuous quality improvement
activities after designs used in business and industry. This has resulted in a
somewhat standardized and possibly limited approach to conducting quality
improvement activities. In contrast, the evaluation paradigm provides a broader
approach because the design of an evaluation may be based on the questions to be
examined, or the design may emerge during the process of conducting the
evaluation. This article examines the design of evaluations used for continuous
quality improvement activities in health care and human service organizations.
Through a case example, the benefits of using alternative evaluation designs are
explored. In particular, use of alternative approaches to gather and evaluate
information about restrictive treatment interventions in a mental health setting
are presented.
PMID- 10183325
TI - The role of the phlebotomy technician. Skills and knowledge required for
successful clinical performance.
AB - An inventory of competencies considered representative of the entry-level
phlebotomy technician's role was developed and validated. A national sample of
certified phlebotomy technicians received through the mail a questionnaire
delineating 44 specific task or knowledge areas and nine higher order work areas.
Respondents rated the specific areas along importance and extent-of-performance
dimensions and rated the higher order areas in terms of importance and time
spent. The importance ratings obtained (which were also scaled by employing the
Rasch measurement model) indicated that knowledge reflected in the inventory was
considered important for successful practice. Approximately 33% of the
questionnaires (175/530) were returned. The results presented here may be
considered by allied health credentialing agencies, employers, curriculum
developers, and educators in defining the phlebotomy technician's work role.
PMID- 10183326
TI - Medicaid managed care in Texas. What have we learned from the pilots?
AB - Texas has a plan for statewide implmentation of Medicaid managed care by 2001.
This article presents evidence from initial demonstration projects, which were
implemented in 1993. The 1st-year experience is described and preliminary effects
are examined in terms of reactions of clients and providers and changes in
utilization patterns and costs of care. Results of the evaluation indicate
implementation difficulties with several operational aspects of managed care,
variable effects in terms of client and provider reaction to the reform, and
little or no change in utilization patterns, but significant cost-savings to the
state. Because of the implementation difficulties identified by the evaluation
and the mixed results regarding effects, further research is recommended to
determine the potential benefit of this reform.
PMID- 10183327
TI - Comparing claims data and self-reported data with the medical record for Pap
smear rates.
AB - The objective of this study was to assess and compare the relative accuracy of
claims data and patient self-reported information with medical records for Pap
smear rates. A retrospective analysis of information obtained from administrative
claims files, patient medical records, and a telephone survey was performed of
400 women age 19 through 75 years who were randomly selected for participation in
the study. The data were obtained from a large multispecialty group practice in
Minneapolis, Minnesota for the study years 1991 through 1993. Information from
administrative claims regarding Pap smear status corresponded highly with
information in the medical record (sensitivity 95% or higher; specificity 95% or
higher; kappa 0.896 or better). Self-reported information from the telephone
survey did not correspond well with medical record information nor with results
in administrative claims.
PMID- 10183328
TI - The reliability of medical student ratings of clinical teaching.
AB - This study estimated the interrater reliability of medical student evaluations of
clinical teaching. Data consisted of 1,570 ratings evaluating 147 faculty over a
4-year period in a 3rd-year internal medicine clerkship. The number of ratings a
typical faculty member receives in a year was also calculated and used to
extrapolate the standard error of measurement for data typically available to
evaluate faculty at different time intervals. The data available to evaluate a
faculty member after 1 year was not adequate, but improved substantially at the 5
to 7-year mark, when a faculty member is typically evaluated for promotion and
tenure.
PMID- 10183329
TI - Applying readily accessible graphical techniques to assess curvilinear
relationships and detect outliers. The case of protective family processes.
AB - The purpose of this article is to use data from a study of protective family
processes to illustrate how readily accessible graphical techniques can
supplement correlation and regression analyses. Graphical techniques can help to
(a) better understand family process data from a descriptive standpoint, (b)
minimize erroneous statistical conclusions, and (c) clarify theoretically
important relationships among variables. Following a brief description of the
substantive area selected for illustration of the graphical techniques, data from
a study employing multimethod measurement procedures (N = 146) are employed to
illustrate two graphical technique applications in the analysis of a predictor
(marital quality) of a study outcome variable (parent-child affective quality).
Instructions for the application of relevant procedures in SAS and SPSS
statistical packages are provided.
PMID- 10183330
TI - Factors that influence health risk behaviors among tanning salon patrons.
AB - A principal components analysis identified the immediate convenience of indoor
tanning (i.e., relaxation, perceived attractiveness of tans) as a major factor
that motivates people to visit commercial tanning salons frequently and
continually. Long-term considerations, such as price, socializing, and perceived
health, also emerged as a motivating factor that was related to tanning
frequency. Furthermore, almost half of the participants mentioned that
regulations restricting indoor tanning would not make them more cautious in their
tanning behavior. Findings confirm several other studies indicating that
knowledge of the danger of UV exposure may have little influence on actual
tanning behavior. Suggestions for alternative approaches that focus on the
perceived attractiveness of tanned skin rather than the susceptibility of
frequent tanners to skin cancer are discussed.
PMID- 10183331
TI - A randomized trial of the impact of certified mail on response rate to a
physician survey, and a cost-effectiveness analysis.
AB - This study's goals were to (a) determine whether sending a survey by certified
mail results in a higher response rate from physicians compared to sending by
first-class mail and (b) evaluate the cost-effectiveness of this method. The
study sample was 409 physicians who were nonrespondents to two previous mailings
of a medical specialty society survey. Eligible physicians were designated at
random to receive a final mailing either by U.S. Postal Service certified mail
including a return-receipt postcard or by first-class mail. There was a higher
response rate from the certified mail group compared with the first-class mail
group (41.3% versus 24.8%; relative risk = 1.66, 95% Confidence interval 1.25,
2.21). A cost-effectiveness analysis showed that the cost per respondent was
higher using certified mail versus first-class mail in the third mailing ($2.77
versus $2.34). Thus, use of certified mail is effective in increasing survey
response but more costly.
PMID- 10183332
TI - Physicians and smoking cessation. Development of survey measures.
AB - Data from a mailed survey to primary care physicians (N = 122) were used to
construct and evaluate psychosocial scales related to performance of smoking
cessation counseling. Scales measuring counseling barriers, self-efficacy, and
motivation demonstrated considerable promise with excellent or reasonable
internal consistency. The correlation for each scale with performance of
cessation counseling and with stage of change was statistically significant.
Physicians who report they are currently assisting patients had higher
performance and self-efficacy rating. Physicians who had participated in formal
smoking cessation training had higher self-efficacy; however, their scores on the
Barriers, Motivation, and Performance Scales did not differ. Further study with a
representative group is encouraged.
PMID- 10183333
TI - Evaluation issues and strategies for community-based organizations developing
women's HIV prevention programs.
AB - This article discusses issues and strategies for program evaluation particularly
useful for community-based organizations (CBOs) involved in the development and
implementation of HIV preventing programs for women. The approach the authors
present is an extension of a traditional public health paradigm suggested for use
in the development and evaluation of violence prevention programs. This study
incorporates Becker's Health Belief Model, which provides a framework for viewing
the influence of various psychosocial variables on health-related behavior, into
this development and evaluation paradigm. Factors influencing the successful
development and evaluation of HIV prevention programs for women are reviewed and
discussed. The purpose of this article is to provide some guidance to CBOs to
strengthen their evaluation strategies and to encourage their use of evaluation
during all phases of program development and implementation.
PMID- 10183334
TI - Evaluation of a school climate instrument for assessing affective objectives in
health professional education.
AB - A conceptual framework for the study of school climate and development of
professional caring ability is proposed that is compatible with research on
learning environment and socialization. Student input characteristics were
measured demographically and through use of previously validated scales from the
Parental Bonding Instrument; student outcome characteristics were measured on the
Caring Ability Inventory for which considerable empirical validity evidence
exists. The primary focus of this evaluation addressed reliability and validity
of an instrument designed to assess learning environment that had not previously
been used in postsecondary education. Four abbreviated School Climate scales were
studied: Respect, Trust, Morale, and Caring. Source data were obtained from the
initial phase of a longitudinal study of baccalaureate nursing students
throughout the United States. Factor analysis, score reliability, and item-total
correlation results indicate the School Climate instrument has indicate the
School Climate instrument has theoretical and practical utility for program
evaluation and improvement in health professional education.
PMID- 10183335
TI - The incorporation of empirical item difficulty data into the Angoff standard
setting procedure.
AB - This study represents an attempt at incorporating empirical item difficulty data
into the Angoff standard-setting procedure without affecting the subjective
judgment of the raters. The Rasch-model ability level corresponding to minimal
competence was estimated for each of 536 items on the American Association of
State Social Work Boards (AASSWB) social work licensure examinations from their
empirical calibrations and Angoff ratings. The mean of these estimates for all
items on a given examination was taken as the level of minimal competence of the
entire examination. This procedure yielded raw passing scores that were 4 to 6
items lower (out of 150) and pass rates that were 7% to 15% higher than those
obtained using the "standard" Angoff procedure.
PMID- 10183336
TI - Cuing effect of "all of the above" on the reliability and validity of multiple
choice test items.
AB - It is generally acknowledged that alternatives such as none of the above and all
of the above should be used sparingly in multiple-choice (MC) items. But the
effect that all of the above has on the reliability and validity of an MC item is
unclear. This study compared the results of a single-response (SRa) item format
that included all of the above as the correct response to a multiple-response
(MR) item format that required examinees to select all of the available
alternatives for a correct response. A crossover design was used to compare the
effect of formats on student performance while item content, scoring method, and
student ability levels remained constant. Results indicated that the SRa format
greatly distorted examinee performance by elevating their scores because
examinees who recognized two or more alternatives as being correct were cued to
select all of the above. In addition, the SRa format significantly reduced the
reliability and concurrent validity of examinee scores. In summary, the MR format
was found to be superior. Based upon new empirical evidence, this study
recommends that whenever an educator wishes to evaluate student understanding of
an issue that has multiple facts, the SRa format should be avoided and the MR
format should be used instead.
PMID- 10183337
TI - The impact of formalization, role conflict, role ambiguity, and communication
quality on perceived organizational innovativeness in the Cancer Information
Service.
AB - Organizational members' levels of perceived innovativeness represent an insider's
viewpoint of the organization's overall approach to innovation. This study tested
a model of the impact of formalization, role ambiguity, role conflict, and
communication quality on perceived organizational innovativeness in the Cancer
Information Service. Data were gathered from self-report questionnaires completed
by organizational members (n = 86) within the Cancer Information Service, a
geographically dispersed federal government health information program that was
implementing innovative intervention strategies related to disseminating health
information to the public. Results indicated that although the predicted model
provided a good overall fit to the data, there were some problematic paths. A
revised model is offered to reconceptualize the relationships among role
conflict, role ambiguity, and communication quality. These results are discussed
in terms of their implications for managers and scholars who hope to understand
the factors that contribute to perceptions of innovativeness in the new
organizational forms emerging in the health service arena. These data suggest
that formalization makes an important contribution to innovation in the highly
uncertain world of new organizational forms.
PMID- 10183338
TI - Responsibility for clinical innovation. A case study in neonatal medicine.
AB - Proper evaluation of clinical innovations and of the process of their diffusion
is essential for the development of sound health care policy. This case study
examines transcutaneous oxygen monitoring in neonatal intensive care, a procedure
that was rapidly adopted in the late 1970s as a scientific breakthrough of great
promise, then all but abandoned within a decade in favor of pulse oximetry, a
still more recent technology. The study incorporates the results of interviews
with representatives of industry as well as biomedical researchers and clinicians
involved with these devices. Factors in technology diffusion are analyzed, with
special attention to those susceptible to change by policy makers. Participants
in the diffusion process also include nurses, hospital administrators, the legal
profession, the news media, and the public, but the pivotal role--and hence
ultimate responsibility--is seen to be that of the physician. The discussion is
presented in the context of a proposed "ethics of evidence" pertinent to medical
decision making.
PMID- 10183339
TI - The reliability of the Diabetes Care Profile for African Americans.
AB - The Diabetes Care Profile (DCP) is an instrument used to assess social and
psychological factors related to diabetes and its treatment. The reliability of
the DCP was established in populations consisting primarily of Caucasians with
type 2 diabetes. This study tests whether the DCP is a reliable instrument for
African Americans with type 2 diabetes. Both African American (n = 511) and
Caucasian (n = 235) patients with type 2 diabetes were recruited at six sites
located in the metropolitan Detroit area. Scale reliability was calculated by
Cronbach's coefficient alpha. The scale reliabilities ranged from .70 to .97 for
African Americans. These reliabilities were similar to those of Caucasians, whose
scale reliabilities ranged from .68 to .96. The Feldt test was used to determine
differences between the reliabilities of the two patient populations. No
significant differences were found. The DCP is a reliable survey instrument for
African American and Caucasian patients with type 2 diabetes.
PMID- 10183340
TI - The use of formative evaluation to assess integrated services for children. The
Robert Wood Johnson Foundation Child Health Initiative.
AB - This article describes the use of formative evaluation in assessing the
feasibility of implementing a new service integration effort. The Child Health
Initiative, a nine-site, national demonstration project funded in 1991 by the
Robert Wood Johnson Foundation, sought to implement systemic change through the
creation of new mechanisms for spending service dollars more flexibly at the
local site. The Child Health Initiative called for developing local child health
monitoring systems, a care coordination mechanism, and a program for
decategorizing the myriad of restrictive categorical public programs serving
children. Most demonstration communities experienced some degree of success in
achieving the first two components, but none was able to implement
decategorization during the 3- to 5-year funding period. Key lessons for
evaluators include the need for (a) a flexible evaluation design that can
sequentially adapt to changes in program implementation, (b) repeated
longitudinal data collection measures to document changes over time, (c)
avoidance of a premature focus on program outcomes, and (d) methods to establish
attribution of outcomes.
PMID- 10183341
TI - Developing and implementing an intervention. Evaluation of an emergency
department pilot on partner abuse.
AB - This article discusses the role of formative and process evaluation in the
development and implementation of a pilot intervention to improve the
identification, treatment, and referral of women abused by their partners who
present to an emergency department (ED). These evaluations were undertaken in
conjunction with an outcome evaluation of training in and use of a five-step
protocol of care piloted in a New Zealand public hospital. The outcome evaluation
showed there was an improvement in identification and acute care of abused women
following the intervention. The article highlights key factors that were relevant
to the intervention's development and implementation, including social context,
development processes, appropriateness for the setting, and level of support from
key stakeholders. Factors identified as key to intervention effectiveness
included its appropriateness for abused women and responsiveness to specific
hospital, department, and staff needs. The key role of formative and process
evaluation in the development and implementation of pilot interventions is
highlighted, and the particular lessons gained from this study have relevance and
application to other interventions.
PMID- 10183342
TI - Quality-of-life assessment in health care research and practice.
AB - This article reviews the different ways in which quality-of-life assessment has
been applied to and has affected health care research and practice. A schema that
describes the steps involved in the ongoing challenge of improving health
outcomes is used to structure the review. The role of quality-of-life assessment
is addressed with regard to: the identification of health problems, the
evaluation of new treatments, the formulation of treatment guidelines and health
policies, the delivery of optimal care in practice, and the assessment of
outcomes in the wider community. The benefit of quality-of-life assessment has
been demonstrated in a number of these areas (e.g., in identifying problems and
evaluating treatments). Its role in other applications (e.g., in clinical
practice to assess patients' needs) shows great promise and requires additional
evaluation.
PMID- 10183343
TI - Use of quality-of-life outcome assessments in current cancer clinical trials.
AB - During the past decade, the importance of integrating quality of life with other
indicators of efficacy in cancer clinical trials has been emphasized. This
article reviews quality-of-life assessment in clinical trial reports. All
empirical studies using patient ratings published in the Journal of Clinical
Oncology from 1992 to 1996 were identified. Of these, 59 articles (4%) included
quality-of-life assessment, most frequently measured by self-report
questionnaires. Most articles reported clinical trials of symptom management or
treatment. Future research needs to specify relationships between quality of
life, toxicity, and survival. Continued development of this field requires more
frequent inclusion of quality of life in clinical studies.
PMID- 10183344
TI - Health-related quality of life. A guide for the health professional.
AB - The importance of evaluating health care in terms of patients' quality of life
has only recently been acknowledged in the context of outcomes research and the
measurement of quality of care. As a health professional, trying to choose the
appropriate health status or health-related quality of life (HRQOL) measure can
be daunting, as one is faced with a bewildering array of choices. The purpose of
this article is to describe the process by which professionals might make a
choice about measures in outcomes research. The article includes examples and
rationale for using generic or disease-specific HRQOL measures. In addition,
examples are provided of HRQOL assessment in two adult chronic disease
applications: asthma and congestive heart failure.
PMID- 10183345
TI - Generic versus disease-specific health status measures. An example using coronary
artery disease and congestive heart failure patients.
AB - The objectives of this study were to evaluate and compare the psychometric
properties of a generic health status measure, the Medical Outcomes Study SF-36,
and a disease-specific health status measure, a modified version of the Chronic
Heart Failure Questionnaire (CHQ), among outpatients known to have coronary
artery disease (CAD) and/or congestive heart failure (CHF). A cross-sectional
analysis of baseline data obtained from 670 outpatients participating in a
randomized controlled clinical trial in the general medicine clinics of a major
academic medical center was performed. The SF-36 was more comprehensive in its
coverage of different health status domains. In contrast, the CHQ had fewer
problems with floor and ceiling effects, was more internally consistent, had
better dimensional reproducibility, and exhibited less factorial complexity.
Although both instruments are appropriate for use among outpatients known to have
CAD and/or CHF, the CHQ has significantly better psychometric properties than
does the SF-36.
PMID- 10183346
TI - Selecting a generic measure of health-related quality of life for use among older
adults. A comparison of candidate instruments.
AB - Selecting an outcomes assessment instrument requires knowledge of their relative
merits, especially head-to-head comparisons. The authors compare health-related
quality-of-life (HRQOL) instruments among older adults for their psychometric
properties and subject burden, specifically the Sickness Impact Profile (SIP) and
Medical Outcomes Study Short-Form 36 (SF-36). Subjects were 282 of 373 eligible
older adults (75.6% response) ranging in age from 65 to 96. SIP scores
demonstrated a strong skew toward low (good health) scores with a mean of 11.1%
(+/- SD 11.5) on the Total SIP index score. Similar components of the SIP and SF
36 were moderately to strongly correlated. The SIP suffered from a ceiling (good
health) scaling effect, and the SF-36 scales also demonstrated some scaling
extremes. These results demonstrate the relative scaling limits, especially the
ceiling effect, of the SIP compared to the SF-36, and in general, the SF-36 is
preferred for use among community-living older adults.
PMID- 10183348
TI - Medicare and state health programs: fraud and abuse; issuance of advisory
opinions by the OIG--HHS. Final rule.
AB - In accordance with section 205 of the Health Insurance Portability and
Accountability Act of 1996, this final rule sets forth the specific procedures by
which the Department, through the Office of the Inspector General (OIG), in
consultation with the Department of Justice (DoJ), will issue advisory opinions
to outside parties regarding the interpretation and applicability of certain
statutes relating to the Federal and State health care programs. The procedures
for submitting a request and obtaining an advisory opinion from the OIG were
established through interim final regulations published in the Federal Register
on February 19, 1997. In response to public comments received on these interim
final regulations, this final rule revises and clarifies various aspects of the
earlier rulemaking.
PMID- 10183347
TI - Changes in surrogate laboratory markers, clinical endpoints, and health-related
quality of life in patients infected with the human immunodeficiency virus.
AB - OBJECTIVE: To evaluate the relationship between laboratory markers of HIV, AIDS
defining events, study discontinuation, and summary scores from the MOS-HIV
Health Survey. METHODS: Secondary analysis of data from a clinical trial of
antiretroviral therapies in advanced HIV-infected patients (N = 940). Clinical
and health-related quality-of-life data were collected over 48 weeks. Linear
regression, logistic regression and survival analyses were performed to evaluate
the relationships between MOS-HIV summary scores, clinical events, and laboratory
markers. RESULTS: Each point increase in PHS resulted in a 3.0% decrease in the
likelihood of developing an AIDS-defining event (p < .05) and a 2.7% decrease in
likelihood of study discontinuation (p < .05). MHS did not significantly predict
clinical events, but did predict study discontinuation (p < .05). From the linear
regression analyses, the change in CD4 counts was a significant predictor of the
change in MHS (p < .01). CONCLUSION: The MOS-HIV summary scores predict clinical
events and study discontinuation in advanced HIV-infected patients.
PMID- 10183349
TI - The transformation of work and the law of workplace accidents, 1842-1910.
PMID- 10183350
TI - Chronic vagus nerve stimulation for treatment of seizures.
PMID- 10183351
TI - Genetic testing for inherited susceptibility to colorectal cancer: part I.
Adenomatous polyposis coli (APC) gene mutations.
PMID- 10183352
TI - Genetic testing for inherited susceptibility of colorectal cancer: part II.
Hereditary nonpolyposis colorectal cancer (HNPCC).
PMID- 10183353
TI - High-dose chemotherapy with autologous stem-cell support for epithelial ovarian
cancer.
PMID- 10183354
TI - Pancreas transplantation.
PMID- 10183355
TI - Partial left ventriculectomy.
PMID- 10183356
TI - Pelvic floor stimulation in the treatment of adult urinary incontinence.
PMID- 10183357
TI - Radioimmunoscintigraphy for prostate cancer.
PMID- 10183358
TI - "Tandem" high-dose chemoradiotherapy with autologous stem-cell support in the
treatment of newly diagnosed or responsive multiple myeloma.
PMID- 10183359
TI - Monolayer slide preparation and automated slide reading systems for cervical
cancer screening--clinical-effectiveness analysis.
PMID- 10183360
TI - The cost-effectiveness of three new technologies to enhance Pap testing.
PMID- 10183361
TI - Special report: comparative efficacy of different types of pneumatic compression
pumps for the treatment of lymphedema.
PMID- 10183362
TI - Special report: pressure-reducing support surfaces in the prevention and
treatment of pressure ulcers: group 1 technologies. Part I.
PMID- 10183363
TI - Death and language: some comments on Haussamen.
AB - Brock Haussamen argues inventively that there are features of language that are
the source of our belief in an afterlife, that something deep about language
prevents us from talking about the dead as if they are really dead. He speaks of
"language as forcing." In this response to Haussamen's article, the author
attempts to show that Haussamen's arguments and examples are not strong enough to
make his point. The major suggestion is that there is more to the "deep
structure" of language than Haussamen has assumed. Once this is realized, it is
easier to see that it is we who choose to speak of the dead as we do. It is we
who choose to believe in an afterlife. Language does no forcing.
PMID- 10183364
TI - Castrating pedophiles convicted of sex offenses against children: new treatment
or old punishment?
PMID- 10183365
TI - Individual privacy interests and the "special needs" analysis for involuntary
drug and HIV tests.
PMID- 10183366
TI - Scientific expert testimony and intellectual due process.
PMID- 10183367
TI - External counterpulsation for treatment of chronic stable angina pectoris.
PMID- 10183368
TI - Intra-articular hyaluronan injections for treatment of osteoarthritis of the
knee.
PMID- 10183369
TI - Minimally invasive coronary artery bypass graft surgery.
PMID- 10183370
TI - Special report: prevention and treatment of pressure ulcers: group 2
technologies. Part II.
PMID- 10183371
TI - Special report: pressure-reducing support surfaces in the prevention and
treatment of pressure ulcers: group 3 technologies and continuous rotational
devices. Part III.
PMID- 10183372
TI - Provide, provide: the economics of aging.
AB - Most older persons face two potentially serious economic problems: (a) declining
earning power and (b) declining health that can be partly offset by increased
utilization of health care. The decline in earning power is largely attributable
to physiological changes and to obsolescence of skills and knowledge. These
adverse effects are exacerbated by public and private policies that reduce the
incentives of older persons to continue work and increase the cost to employers
of employing older workers. The problems of earnings replacement and health care
payment are usually discussed separately, but there are several reasons why they
should be considered together. First, there are often tradeoffs between the two.
Money is money, and for most people there is never enough to go around. This is
self-evident where private funds are concerned. Low-income elderly, for
instance, frequently must choose between expensive prescription drugs and an
adequate diet. For middle-income elderly, the choice may be between saving on
medigap insurance or forgoing an airplane trip to a grandchild's graduation.
Difficult choices are also inherent in the allocation of public funds. The same
tax receipts that could be used to maintain or increase retirement benefits could
be used to fund additional care, and vice versa. In discussing these tradeoffs,
some analysts assert that people will gladly give up other goods and services for
medical care that cures illness, relieves pain, or restores function. Others
believe that some people would forgo some health insurance in order to maintain
access to other goods and services. A second reason for looking at the two
problems together is that they pose similar questions for public policy. How
much should each generation provide for its own needs in old age, and how much
should be provided by the generations that follow? How much provision should be
voluntary, how much compulsory? How much intra-generational redistribution is
appropriate after age 65? How well can private markets serve the elderly's
desire for annuities and health insurance, and when are public programs more
efficient? Finally, the problem of health care payment is approaching that of
earning replacement in economic importance and, by 2020, will far exceed it.
Declining health after age 65 results in substantial increase in use of
prescription drugs, hospital admissions, repair or replacement of parts of the
body, rehabilitation and physical therapy, and assistance with activities of
daily living. New technologies offer great promise for offsetting the health
problems of aging, but often at considerable expense. Overall, per capita
expenditures for health care after age 65 are between three and four times as
great as for those under 65. This presentation will focus primarily on the (thus
far) inexorable increase in consumption of health care by older Americans. If
this increase continues and if the government's share of the total remains
unchanged, the tax burden on younger cohorts could become intolerable.
Concomitantly, if the private share remains unchanged, the ability of the elderly
to obtain other goods and services would be sharply diminished. Although the
emphasis of the session will be on aggregate and average results, levels and
trends in income inequality among the elderly will also be examined and compared
with inequality at younger ages. The session will conclude with a discussion of
changes that might avert the economic and social crises foreshadowed in the data.
PMID- 10183373
TI - Authenticating healthcare quality: information and accountability.
PMID- 10183374
TI - The Federal Employees Health Benefits program: what lessons can it offer
policymakers?
PMID- 10183375
TI - Restructuring the VA health care system: safety net, training, and other
considerations.
PMID- 10183376
TI - Dual diagnoses: the challenge of serving people with concurrent mental illness
and substance abuse problems.
PMID- 10183377
TI - Direct-to-customer advertising of prescription drugs.
PMID- 10183378
TI - Ropinirole: new preparation. Wait for more convincing data.
AB - In previously untreated parkinsonian patients at an early stage of the disease,
three comparative trials have shown that, during the first six months of
treatment, the effect of ropinirole on motor symptoms almost equates to that of
levodopa and is a little better than that of bromocriptine monotherapy. Until
these trials have been completed (they are planned to last for 3 to 5 years), it
will be impossible to know whether the postponement of dopatherapy with
ropinirole administration influences the long-term outcome of Parkinson's
disease. In patients already on levodopa who have mobility fluctuations, the only
demonstrated effect in one trial was that the addition of ropinirole allowed the
daily dose of levodopa to be reduced. However, this is a surrogate end point
with no clinical relevance. A single comparative trial, versus another dopamine
agonist, bromocriptine, is available, but its complex methodology makes it
impossible to draw firm conclusions. The adverse effects of ropinirole are the
same as those of other dopamine agonists. Again, this means that the assessment
of ropinirole must continue to determine whether the drug carries an increased
risk of dyskinesias or psychological effects.
PMID- 10183379
TI - Alendronic acid: new preparation. Limited efficacy, risk of oesophagitis.
AB - After 3 years of alendronic acid treatment in post-menopausal women with a
history of vertebral fracture, a large clinical trial has shown a reduction in
the incidence of vertebral, hip and wrist fractures with clinical repercussions.
As regards vertebral fractures with clinical repercussions, 1 000 osteoporotic
women would have to be treated for three years to avoid 27 fractures. Alendronic
acid has not been compared with etidronate, but, in our opinion, it has better
evidence for its efficacy. Treatment can be offered only to women with a history
of osteoporotic fractures who strictly follow the necessary precautions. The
tablets must be taken in the morning on an empty stomach, with a large glass of
water while seated upright or standing, and avoiding lying down for at least
thirty minutes after. These precautions reduce the risk of oesophagitis and
oesophageal ulceration. Pending the results of an ongoing trial of alendronic
acid in this setting, hormone replacement therapy is the only treatment warranted
in women with no history of osteoporotic fracture.
PMID- 10183380
TI - Liposomal daunorubicin: new preparation. Kaposi's sarcoma: occasional remission.
AB - Liposomal daunorubicin rarely leads to complete remission of the unsightly
mucocutaneous lesions Kaposi's sarcoma. One trial comparing liposomal
daunorubicin with the ABV protocol (doxorubicin + bleomycin + vincristine) showed
no statistically significant difference between the treatments in terms of
efficacy or overall tolerability. Liposomal daunorubicin caused less hair loss
and neuropathy, both of which can affect these patients' quality of survival, but
it was more likely to cause neutropenia, sometimes requiring the use of
haematopoeitic growth factors. There is some evidence that the liposomal
formulation reduces the cardiotoxicity of daunorubicin, but this has to be
confirmed, especially in the long term. It is not known whether increasing the
dose of daunorubicin leads to better clinical efficacy. However, patients who
relapse when liposomal daunorubicin is withdrawn may receive the drug again,
without observing a cumulative dose limit, provided that cardiac function remains
normal on the basis of tests recommended in the approved summary of product
characteristics.
PMID- 10183381
TI - Vigabatrin: new indication. An advance in infantile spasms.
AB - In children with infantile spasms, vigabatrin monotherapy has been assessed in
three published comparative trials. The small numbers of patients make it
impossible to draw precise conclusions on effectiveness. However, a few days'
treatment with a dose of about 100 mg/kg/day clears infantile spasms in a larger
proportion of cases than a placebo or steroids. Vigabatrin seems to be more
effective in Bourneville disease. The effect is sometimes transient: despite
continued treatment, spasms or other types of epilepsy occur in approximately 50%
of patients who are initially improved. In a trial versus ACTH, the lesser
initial efficacy of vigabatrin was partly offset by a lower incidence of relapse
and other types of seizures. Vigabatrin is effective in some children who are
resistant to ACTH or steroids. As with steroids and ACTH, there is no proof that
vigabatrin improves the long-term psychomotor development of these children. In
comparative trials the incidence of adverse events was statistically lower on
vigabatrin than on steroids. Most of the events were relatively mild
neuropsychological effects, but a question mark still hangs over the possible
neurotoxicity or oculotoxicity of vigabatrin during long-term administration.
PMID- 10183382
TI - Ifosfamide: new idications-new dose strength. Limited evidence of effectiveness.
AB - In three new approved indications (non Hodgkin's lymphoma, Hodgkin's lymphoma and
acute lymphoblastic leukaemia) and in three previously existing indications
(ovarian cancer, soft tissue sarcomas and osteogenic sarcomas), non comparative
trials show that ifosfamide can induce tumour regression in patients who relapse
after a first course of chemotherapy (sometimes containing cyclophosphamide).
But clinical assessment has not yet formally demonstrated that this leads to a
significant increase in survival time and/or quality of life, mainly because of
toxicity. In cervical cancer, a new indication, a comparative trial shows higher
tumour response rates with the ifosfamide + cisplatin combination than with
cisplatin alone. However, the greater toxicity of the combination and the lack
of any increase in survival must both be taken into account. In breast cancer and
lung cancer comparative trials show no difference in efficacy between
cyclophosphamide and ifosfamide, while toxicity may be worse with ifosfamide.
Ifosfamide has no specific value in these approved indications. The same applied
to ENT cancer, against which ifosfamide seems to have little activity.
PMID- 10183383
TI - Topotecan: new preparation. No proven benefit.
AB - Topotecan does not convincingly alter the grim prognosis of ovarian cancer in
failure or relapse after treatment with platinum salts. The only comparative
trial has not yet been published; available results suggest that 20% of women had
at least a partial response on topotecan, compared to 14% on paclitaxel (no
statistically significant difference). The place of paclitaxel in the treatment
of ovarian cancer also remains to be determined, especially in combination with
other drugs. Like paclitaxel, topotecan has marked haematological and
gastrointestinal toxicity: nausea, vomiting, diarrhoea and stomatitis. Topotecan
solution does not contain the solvent Cremophor EL degrees , contrary to
paclitaxel solution. It does not therefore require preliminary steroid
administration, and does not prohibit the use of PVC-based infusion devices.
PMID- 10183384
TI - Benfluorex: what use? A second look. Poor assessment file.
AB - The clinical file on the value of benfluorex for hypertriglyceridaemia is highly
inadequate. No clinical trials have been done with morbidity or mortality as end
points. Available placebo-controlled trials are small, methodologically weak in
most cases, and their results regarding triglyceride levels are contradictory.
None of the three trials comparing benfluorex with a fibrate is interpretable,
because of methodological problems.
PMID- 10183385
TI - Milnacipran: new preparation. Tricyclics remain first-line antidepressants.
AB - Several placebo-controlled trials have shown that milnacipran, 100 mg/day in two
doses, is an effective antidepressant in both the ambulatory and hospital
settings. Comparative trials against tricyclic antidepressants (imipramine and
clomipramine) failed to show that milnacipran was any more effective.
Milnacipran has not been compared with specific or non specific MAOI
antidepressants. As regards non tricyclic-non MAOI antidepressants, milnacipran
has been compared only to two specific serotonin reuptake inhibitors, fluvoxamine
and fluoxetine. The trials cannot convince us of a difference in efficacy
between the two types of treatment. The claimed superiority of milnacipran over
serotonin reuptake inhibitors is not based on firm evidence of better efficacy or
fewer adverse effects. The overall tolerability of milnacipran is similar to
that of fluoxetine and fluvoxamine. Relative to the tricyclic antidepressants,
milnacipran has fewer atropinic effects (sedation and sweating). In contrast, it
cause more dysuria, and cannot, therefore, replace tricyclics in elderly men with
prostate disorders. Tricyclics remain the preferred first-line antidepressant
drugs. When they are contraindicated or poorly tolerated, many other
antidepressants with well-documented risk-benefit ratios are available.
PMID- 10183387
TI - Drug-induced benign intracranial hypertension.
PMID- 10183386
TI - Gingival hyperplasia due to calcium antagonists.
PMID- 10183388
TI - Terminal care: not just pain management.
AB - Palliative care should aim at being rapidly effective on all symptoms. Several
disorders are common and require routine management: mouth problems,
constipation, nausea. Skin care is essential for comfort and dignity. Team-work
is a pre-requisite for home-based palliative care.
PMID- 10183389
TI - Tamsulosine: new preparation. Capsules: alphablocker.
AB - Tamsulosine, an alphablocker, is moderately effective on the symptoms of benign
prostatic hyperplasia. Its adverse effects are of the same order as those of
other alphablockers already on the market in France (alfuzosine and prazosine);
there is notably a risk of postural hypotension. There is no proof that the risk
benefit ratio of tamsulosine is any better than that of other alphablockers or 5
alpha-reductase inhibitors (finasteride).
PMID- 10183390
TI - Miltefosine: new preparation. Solution for cutaneous application.
AB - In patients with breast cancer and skin metastases, topically applied miltefosine
solution yields at least partial regression of the lesions in approximately a
quarter of patients when used as an adjunct to standard treatment (surgery,
radiotherapy, systemic chemotherapy or hormone therapy) or when standard
treatments are contraindicated. Complete remission was achieved in only 6% of
cases in non comparative trials, and the median duration before progression
resumed was 6 months. Miltefosine can have many local adverse effects.
PMID- 10183391
TI - Why use calcitonin? New indication: no proven utility in the treatment of
osteoporosis.
AB - Four placebo-controlled clinical trials on calcitonin show a statistically
significant difference in favour of the analgesic effect of calcitonin in
patients suffering from recent osteoporotic compression of the vertebrae.
However, the clinical value of the difference has been poorly established.
Calcitonin frequently causes side effects, and the current state of assessment
has not established whether the risk-benefit ratio is better than that of non
specific analgesics. Finally, calcitonin treatment is more costly than using non
specific analgesics.
PMID- 10183392
TI - Tramadol: new preparation. Capsules: central analgesic; step 2 on the WHO scale.
AB - The clinical assessment file on tramadol is of low quality. In acute
postoperative pain and chronic pain there is no proof that tramadol has a better
risk-benefit ratio than the paracetamol + codeine combination or other step 2
analgesics in the World Health Organisation classification. Like all other
central analgesics, tramadol can have neuropsychological adverse effects,
especially a risk of dependence and misuse.
PMID- 10183393
TI - Epoetin beta: new indication. Preparation for IV-SC injection: erythrocyte growth
factor.
AB - According to an unreliable meta-analysis, epoetin beta reduces the number of
premature neonates needing transfusions for anaemia by 18% on average. When such
children do require transfusions, two comparative trials have shown a reduction
in the frequency of transfusions and total volume of blood transfused, but the
clinical consequences were not studied. Thus clinical experience to date is too
limited to rule out a risk of possibly severe adverse events. Furthermore,
prescription of epoetin beta must be accompanied by iron supplementation, whose
optimal dose and route of administration have not been established. The cost
benefit ratio of epoetin beta in the prevention of anaemia in premature infants
must be thoroughly assessed in the context of national health systems.
PMID- 10183394
TI - Pneumococcal vaccine: a second look. Solution for SC or IM injection:
pneumococcal vaccine.
AB - Pneumo 23 degrees , like the pneumococcal vaccines tested in randomised
comparative trials, may slightly reduce the incidence of pneumococcal pneumonia
in subjects with no particular risk factors, but fails to alter the overall
incidence of pneumonia or its related mortality. In subjects at high risk of
infection, pneumococcal vaccines have not been proven clinically effective in
well-conducted trials. According to available retrospective studies Pneumo 23
degrees may, at best, slightly reduce the risk of severe pneumococcal infection.
It has, however, no demonstrated effect on mortality and does not protect
against pneumococci with diminished sensitivity to penicillin.
PMID- 10183395
TI - Severe heart valve disease on appetite suppressants.
PMID- 10183396
TI - Acute methotrexate poisoning.
PMID- 10183397
TI - Adverse haematological effects of ticlopidine.
PMID- 10183398
TI - Cardiac risk with diphemanil methylsulfate in infants.
PMID- 10183399
TI - History and physical findings in recent low back pain and sciatica.
PMID- 10183401
TI - Correct use of refrigerators for vaccine storage.
PMID- 10183400
TI - Risks of assisted reproduction.
PMID- 10183402
TI - No surgery for moderate symptomatic carotid stenosis.
PMID- 10183403
TI - New, accurate 3-D imaging may prevent breast biopsies.
PMID- 10183404
TI - Nepal sets up telepsychiatry program.
PMID- 10183405
TI - 1998 construction design survey.
AB - Healthcare construction and design firms are discovering new worlds of
opportunity--some domestic, some international and some unconventional. Emergency
room renovation and construction work is drawing more attention, as are overseas
projects and facilities designed with alternative medicine in mind. The number of
projects rose 11% in 1997, but the overall cost of completed projects stayed flat
compared with the previous year.
PMID- 10183406
TI - Warning! AbTox sterilizers recalled--FDA is on the case.
PMID- 10183407
TI - Image and database provide health management clues.
PMID- 10183408
TI - Computerized medical records.
PMID- 10183410
TI - Dictionary for health.
PMID- 10183409
TI - The market research encyclopedia.
AB - Market research can be a complicated and complex process nowadays, especially
when it involves sophisticated techniques with names like probabilistic sampling,
Box-Jenkins, or conjoint analysis. There is a need for a guide that will help
managers determine the dimensions of the task, the resources that must be
summoned, the data required, and other key elements. Here, from the head of
market research at General Motors, is such a guide in outline form. Vincent P.
Barabba walks the reader through the five major stages of the research effort.
Each stage is represented in one table, and together the tables combine into a
mammoth foldout for easy perusal. The stages are: 1. Assess the market
information needs. 2. Measure the marketplace. 3. Store, retrieve, and display
the data. 4. Describe and analyze market information. 5. Evaluate the research
and assess its usefulness. Comprehensiveness is a hallmark of the "encyclopedia."
In the second table, for example, one of the headings under "nonprobabilistic
data" is "central location interviewing." Barabba lists the limitations of this
kind of research: "Very expensive; responses in this artificial environment may
not reflect responses in the market; complicated logistics; development of test
product can be time consuming and expensive."
PMID- 10183411
TI - An expanded perinatal bereavement support committee: a community-wide resource.
AB - While perinatal health care professionals have discussed individual methods to
support bereaved parents after a perinatal death (miscarriages, stillbirths, or
neonatal deaths), there needs to be a comprehensive approach to perinatal
bereavement support that extends not only to bereaved family members, but to the
perinatal staff and the medical and nonmedical community. To facilitate such
support, a perinatal hospital bereavement support committee was established. Its
functions are described, including the development of hospital bereavement
protocols, educational programs for all medical and nonmedical staff, and the
establishment of local support groups.
PMID- 10183412
TI - Laboratory cost analysis: a practical approach.
AB - This article presents a practical method for performing a cost analysis for the
smaller laboratory for which computerized methods may be unavailable or
unappealing. An overview of cost accounting as it fits into planning functions is
presented, and three common methods for performing such analyses and appropriate
applications are described. The concept of breakeven analysis and its uses are
presented. Finally, a worksheet approach to cost analysis is presented, including
examples that demonstrate proper use. The worksheets, although not universally
applicable without modifications, use a stepwise process to achieve a simplistic
but useful cost analysis. Readers are encouraged to adapt these worksheets to
their own operations.
PMID- 10183413
TI - The impact of biosensors on the clinical laboratory.
PMID- 10183414
TI - Medicare program; Medicare coverage of hepatitis B vaccine for high and
intermediate risk individuals, hemophilla clotting factors and certain X-ray
services--HCFA. Final rule.
AB - This final rule implements section 2323 of Public Law 98-369, the Deficit
Reduction Act of 1984, which provides Medicare coverage for hepatitis B vaccine
for those individuals who are eligible for Medicare and at high or intermediate
risk of contracting hepatitis B. This final rule defines those individuals who
are at high or intermediate risk of contracting hepatitis B. It also implements
section 2324 of Public Law 98-369, which provides coverage for the self
administration of hemophilia clotting factors and the items necessary for their
administration to Medicare eligibles. In addition, this final rule clarifies
regulations governing Medicare coverage of certain x-ray services.
PMID- 10183415
TI - Making room in the market-place. 75th annual Catholic Health Assembly.
AB - In a world that is rapidly changing, healthcare stands in the midst of the
maelstrom. Yet the one thing that everybody agrees on is the need for more
change. The 75th Annual Catholic Health Assembly brought together members of the
Catholic healthcare community to reflect on the need to reform the U.S.
healthcare system. Together, they examined the problems, the proposals, and the
processes for change. At the assembly, marking the 75th anniversary of the
founding of CHA, the ministry's leaders reaffirmed their commitment to the
founders' values and looked at practical ways to fulfill their mission to serve
the poor and most vulnerable among us.
PMID- 10183416
TI - Words of a feather.
PMID- 10183417
TI - What's in a name? Discharge planning? Case management? Managed Care?
PMID- 10183418
TI - Management must role for physicians.
AB - It is not the same subject that was projected in the '70s when quality assurance
leaped on the health care scene. As complex as quality assurance is, contemporary
discussions of quality are much more multifaceted. At the core of health care
quality, however, is clinical practice. The consensus among speakers at the
College's National Conference of Physician Executives in May in San Antonio,
Tex., is that medical quality will not be managed in the interests of patients,
buyers, and providers in the absence of significant involvement by physician
executives.
PMID- 10183419
TI - Comparing RCPs to physicians for the description of lung sounds: are we accurate
and can we communicate?
AB - Precise communication among clinicians of chest-auscultation findings depends on
use of standardized nomenclature for lung sounds. To identify the current
practice of clinicans in describing lung sounds, we surveyed physicians and
respiratory care practitioners (RCPs). MATERIALS AND METHOD: Surveys were
specifically designed to identify: (1) whether RCPs and physicians use similar
terms to describe adventitious lung sounds (ALS), (2) whether changes are
occurring in response to the recommendations of the ATS-ACCP Ad Hoc Subcommittee
on Pulmonary Nomenclature, and (3) whether RCPs and physicians differ in their
ability to accurately recognize ALS. We surveyed 156 RCPs at the 1987 Annual
Meeting of the American Association for Respiratory Care and 223 pulmonary
physicians (PPs) and 54 nonpulmonary physicians (NPPs) at the 1988 Annual Meeting
of the American College of Chest Physicians. Each survey participant was required
to listen to five examples of ALS using earphones and an audiocassette player and
then to write 'free-form' descriptions of what they heard. (All participants
listened to the same ALS.) RESULTS: Fine crackles and high-pitched monophonic and
polyphonic wheezes were readily recognized by the majority of RCPs and
physicians. Fine crackles were described as rales or crackles; high-pitched,
monophonic wheezes were described as stridor or wheezes; however, high-pitched,
polyphonic wheezes were usually described as wheezes. RCPs and physicians used a
variety of terms to describe coarse crackles and rhonchi. The term rhonchi was
frequently used inappropriately by all groups surveyed. There were no significant
differences between PPs and RCPs in their ability to accurately recognize
adventitious lung sounds; however, PPs were superior to NPPs (p less than 0.05)
in this regard. PPs were superior to RCPs and NPPs (p less than 0.05) in
appropriately using the term 'fine' for the description of crackles. CONCLUSION:
All three groups of clinicians need to improve their ability to recognize and
describe lung sounds.
PMID- 10183420
TI - A landmark for home care.
PMID- 10183421
TI - Coding notes ... ICD-10.
PMID- 10183422
TI - One small step for AMRA, one giant leap for the medical record profession: the
Health Information Management Initiative.
PMID- 10183423
TI - Total quality management.
PMID- 10183424
TI - Teach your children well.
PMID- 10183425
TI - Strengthening the corporate culture.
PMID- 10183426
TI - FAHS (Federation of American Health Systems) 1991 conference and business
exposition.
PMID- 10183427
TI - Nation's governors to develop health care plan.
PMID- 10183429
TI - Super sessions in Seattle: 1990 annual meeting report. Information,
communication, and quality management: assets to invest.
PMID- 10183428
TI - AIDS at the beginning of the second decade.
PMID- 10183431
TI - Controlling cost, expanding access: what are the limits?
PMID- 10183430
TI - A revolution in quality assurance.
PMID- 10183432
TI - Medicare, guidelines and new expectations.
PMID- 10183433
TI - Looking at the health care script for the '90s.
PMID- 10183434
TI - Pa. hospitals fail to rein in governments.
PMID- 10183436
TI - Information technology and the healthcare executive.
PMID- 10183435
TI - The Healthcare Forum/3M visionary leadership conference.
PMID- 10183437
TI - American Hospital Association v. NLRB: can the NLRB promulgate rules establishing
per se appropriate bargaining units for acute care hospitals?
PMID- 10183438
TI - Ethical concerns in managing a women's health program.
PMID- 10183439
TI - No-code order alleged to lack patient's consent.
PMID- 10183441
TI - North Carolina court rules ambulatory surgery center exempt from property tax.
PMID- 10183440
TI - Court rejects challenge to hospital peer review action.
PMID- 10183442
TI - The realities of non-executive directors in the NHS.
PMID- 10183443
TI - Local governments call for health care reform.
PMID- 10183444
TI - Designing appropriate health care environments.
PMID- 10183445
TI - ICD-9-CM Coordination and Maintenance Committee meeting.
PMID- 10183446
TI - Recent cases interpret the Tarasoff duty to warn.
PMID- 10183447
TI - Cruzan to Roe and back.
PMID- 10183448
TI - Mandatory AIDS testing opposed.
PMID- 10183449
TI - Prevalence of AIDS burdens healthcare programs for drug abusers, panel told.
PMID- 10183450
TI - The Third-Wave Asbestos Conference: high drama in science.
PMID- 10183451
TI - Another Cruzan outcome: Nevada affirms right to die.
PMID- 10183453
TI - Burden of proof in patient dumping cases.
PMID- 10183452
TI - PPO criteria for selecting hospitals.
PMID- 10183454
TI - Comment: Curran v. Bosze; disposing of an incompetent donor consent case: the
role of parental autonomy and bodily integrity.
PMID- 10183455
TI - California's Wickline decision revisited.
AB - In a recent California appellate decision, Wilson v. Blue Cross of Southern
California, 222 Cal. App 3d 660, 271 Cal Rptr 876 (2d Dist., 1990), the court cut
back on its earlier decision in Wickline v. State of California, 192 Cal. App. 3d
1630, 239 Cal Rptr 810 (2d Dist. 1986), which had provided substantial protection
for third-party payers against liability for utilization review decisions. The
Wilson decision not only limits Wickline to its particular facts, but also
criticizes some of its rationale.
PMID- 10183456
TI - Life and death after Cruzan.
PMID- 10183457
TI - DME (durable medical equipment) antitrust: Venice Hospital, Round III.
PMID- 10183458
TI - When may siblings donate organs?
PMID- 10183460
TI - The wall of confidentiality around Joint Commission survey reports continues to
crumble.
PMID- 10183459
TI - Prompt malpractice insurer notice necessary.
PMID- 10183461
TI - Court rules utilization review organization, its physician consultant, and
insurer subject to suit.
PMID- 10183462
TI - Tennessee ruling deals blow to economic credentialing.
PMID- 10183463
TI - Management of the HIV-positive employee.
PMID- 10183464
TI - Determining patient competency in treatment refusal cases.
PMID- 10183465
TI - Quality assurance vs. quality improvement.
PMID- 10183466
TI - How to create a new image.
PMID- 10183467
TI - Linking quality, productivity.
PMID- 10183468
TI - Wilson v. Blue Cross: liability of payor to patient injured by early discharge.
PMID- 10183469
TI - Forced cesarean case leads to policy on pregnancy rights.
PMID- 10183471
TI - Hospital liability predicated on corporate negligence theory.
PMID- 10183470
TI - Implementing the congressional purpose of the immunity and attorneys' fees
provisions of the Health Care Quality Improvement Act.
PMID- 10183472
TI - Court rules substantial compliance with medical staff bylaws sufficient for
procedural fairness.
PMID- 10183473
TI - IBI (International Bioethics Institute) conference takes organizational reins in
steering ethics committees.
PMID- 10183474
TI - Refusal to treat AIDS patients is discrimination.
PMID- 10183475
TI - Recovery centers: alternative or duplication?
PMID- 10183476
TI - New cleanliness standards set for healthcare linen providers.
AB - Healthcare facilities must pass strict standards to receive accreditation.
Included on the inspection checklist are linen and laundry operations. At TRSA's
15th Annual Healthcare Seminar, a hospital accreditor provided rental operators
with an inside look at scoring guidelines used to rate hospital linen and laundry
operations.
PMID- 10183477
TI - How much are you liable for others' negligence?
PMID- 10183478
TI - Are state nonprofit hospitals exempt from antitrust laws and RICO (Racketeer
Influenced and Corrupt Organizations Act).
PMID- 10183479
TI - BCBS must pay autologous bone marrow transplants.
PMID- 10183480
TI - Medicare must pay bankrupt hospital.
PMID- 10183481
TI - A pyramid strategy for effective materiel management.
AB - Citing an impressive 22-24% average savings on product price without affecting
quality, the user or the patient, Mr. Olsen explains the materiel management
strategy in effect at Humana Inc. The author emphasizes that the pyramidal
structure of the strategy facilitates a step-by-step process until the ultimate
goal is reached--providing quality health care at a reasonable cost.
PMID- 10183482
TI - An update on national efforts to manage private sector utilization review.
PMID- 10183483
TI - Right to die, forced to live: Cruzan v. Director, Missouri Department of Health.
PMID- 10183484
TI - Hospital choice: empirical verification of a proposed taxonomy, contrasting men
and women.
AB - This is a summary of an empirical verification of a hospital choice taxonomy.
Four focus groups were executed followed by a telephone survey of 400
individuals. The situation studied was one where the persons involved had a
choice (no physician influence or emergency), reflecting the present motion to
more proactive health care. No major differences in rank order of factors were
found for men versus women; men ordered choice factors differently based on
primary physician type (MD/DO).
PMID- 10183485
TI - Education for staff is best deterrent to OR drape fires.
PMID- 10183486
TI - Colloquy addresses integrity of pastoral care in institutions.
PMID- 10183487
TI - Windmills on their minds.
PMID- 10183488
TI - NLRB hospital union rules upheld by Supreme Court.
PMID- 10183489
TI - AIDS-infected health care workers: confidentiality, practice issues.
PMID- 10183490
TI - The Medicaidization of certified home health care in New York City.
AB - In New York City, Medicaid has replaced Medicare as the primary payor of
certified home health care agencies. This shift has made agencies vulnerable to
policy changes and budget cutbacks, changed the client population, and put new
demands on service delivery.
PMID- 10183491
TI - The District of Columbia Medicaid crisis.
PMID- 10183492
TI - Joint Assembly of the Catholic Health Associations of Canada and the United
States, Montreal, Quebec, June 9-12, 1991.
PMID- 10183493
TI - Tube feeding and the permanently unconscious: the Supreme Court's decision in
Cruzan.
AB - In the recent case of Cruzan v. Director, Missouri Department of Health, a
majority of the United States Supreme Court voted to affirm a Missouri decision
rejecting the request of guardians for removal of tubes used to provide nutrition
and hydration to a woman in a persistent vegetative state. This article analyzes
the Court's decision, focusing specifically on the concurring and dissenting
opinions in the case, and discusses the implications of this decision for the
states.
PMID- 10183494
TI - Moore v. Regents of the University of California--physician's duty to disclose
use of patient's cells in research.
PMID- 10183495
TI - 'Emphasis must shift to long-term care'.
PMID- 10183497
TI - Research conference focuses on group practice-hospital relationships.
PMID- 10183496
TI - Communicating a shared vision.
PMID- 10183498
TI - Need for standards in medical communication.
AB - Recent progress in clinical informatics resulted in two new tools: a
comprehensive medical nomenclature and a prototype medical text processor. The
direction of further progress is apparent. The technology is ready for large
scale computerization of health care documentation. The new progress-limiting
factors seem to be related to the reorientation of the record writers and the
entire health care industry. The true challenge of the 1990s is to make clinical
data readily available, without jeopardizing the cherished values of medical data
confidentiality and provider privacy.
PMID- 10183499
TI - Privacy rights and HIV status.
PMID- 10183500
TI - Forum: In sickness and in health--the role of the ICD in the United States health
care data and ICD-10.
PMID- 10183501
TI - Community benefit and tax exemption--topics of Trustee Forum.
PMID- 10183502
TI - Legal action and 'confusion' likely to spring from high court's right-to-die
decision.
PMID- 10183503
TI - Starting off on the right track: ASIM's 1990 National Leadership Conference.
PMID- 10183504
TI - Getting fit for the future: ASIM's 1991 Leadership Conference.
PMID- 10183505
TI - Allergic drug reactions: identification and management.
AB - Any attempt to distinguish allergic drug reactions from other adverse drug
reactions (ADRs) can be complicated by the fact that terminology in this area has
not been standardized. True allergic reactions are those resulting from
immunologic causes, and their prevalence is only 6 to 10% of all ADRs. A number
of factors predispose individuals to drug allergies--the recognition of which
might aid the healthcare professional in diagnosing these reactions--and other
criteria can be helpful in the process. In order to successfully separate
pseudoallergic from allergic from other adverse drug reactions, the clinician
must proceed with caution and suspicion. When foreseeable allergic reactions
cannot be prevented, measures can be taken that might reduce their impact.
PMID- 10183506
TI - Standards for electronic patient records.
PMID- 10183507
TI - No free ride. Physician certificates and ambulance transport.
PMID- 10183508
TI - Six models of patient-focused care.
PMID- 10183509
TI - Laboratorians: on the front lines of exposure.
PMID- 10183510
TI - So far, so good?
PMID- 10183512
TI - The quality of black family life in Boston in the twenty-first century.
Conference sponsored by Boston University on November 15, 1986.
PMID- 10183511
TI - Supreme Court expands view of interstate commerce in peer review proceeding.
AB - At the end of May, the U.S. Supreme Court allowed an antitrust claim by a
physician against a hospital for an allegedly improper peer review proceeding.
Previously, hospitals were allowed to defend against antitrust claims regarding a
peer review decision involving one physician on the grounds that the activities
did not affect interstate commerce. The Supreme Court has apparently removed this
defense by letting stand a Court of Appeals decision allowing a physician's
antitrust claim against a hospital that has suspended his privileges.
PMID- 10183513
TI - Hemophilia and AIDS: dealing with nurse burnout.
AB - AIDS has drastically changed the field of caring for hemophiliacs for many health
care professionals: where once they helped people to lead normal lives, they now
must make the HIV-infected hemophiliac deal with the implications of AIDS. This
new stressful responsibility has created a high burnout rate for hemophilia
nurses.
PMID- 10183514
TI - Better-informed clients will move industry forward. Roundtable discussion.
PMID- 10183515
TI - Wilson v. Blue Cross: a case synopsis.
PMID- 10183516
TI - Special report. What the experts advise. Managing the prescription drug benefit.
PMID- 10183517
TI - Special report. What the experts advise. Ambulatory health care: a growing
concern.
PMID- 10183518
TI - Special report. What the experts advise. The challenges in mental health care
benefits.
PMID- 10183519
TI - Effective sexual harassment policies: unexpected lessons from Jacksonville
Shipyards.
AB - Although many employers recognize the need for an effective sexual harassment
policy, they have received only limited guidance from the EEOC and the courts on
how to draft and implement one. This article examines a recent decision, Robinson
v. Jacksonville Shipyards, in which the court imposed a comprehensive sexual
harassment policy. This article suggests that employers should consider adopting
similar policies to better protect themselves from liability for sexual
harassment.
PMID- 10183521
TI - Inaccurate responses on staff application forms have serious consequences.
PMID- 10183520
TI - Look for more employers to become their own providers.
PMID- 10183522
TI - Causes and consequences of rural small hospital closures from the perspectives of
mayors.
AB - Mayors of rural towns whose small general hospitals closed between 1980 and 1988
were surveyed. Only hospitals that were the sole hospitals in their towns and
that had not reopened were included in the survey. Of the 132 hospitals meeting
these criteria, 130 (98.5%) of the mayors of their communities responded to the
survey. The typical study hospital had 31 beds, with an average daily census of
12. Three fourths of the hospital closures were in the North-Central and South
census regions. Half of the hospital closures were for hospitals that were 20
miles or more from another hospital. Mayors attributed the closure of their
hospitals primarily to governmental reimbursement policies, poor hospital
management and lack of physicians. To a lesser extent, they also implicated
competition from other hospitals, reputation for poor quality care, lack of
provider teamwork, and inadequate hospital board leadership. Respondents reported
they had little warning that their hospitals were in imminent danger of closing.
Warnings of six months or less were reported by 49 percent of the mayors; only 33
percent of mayors of towns with for-profit hospitals reported having more than
six months warning. Of the 132 hospital buildings that closed, only 38 percent
were not in use in some capacity in the summer of 1989. Most were being utilized
as some form of health care facility such as an ambulatory clinic, nursing home,
or emergency room. More than three fourths of the mayors felt access to medical
care had deteriorated in their communities after hospital closure, with a
disproportionate impact on the elderly and poor. Nearly three fourths of the
mayors also perceived that the health status of the community was worse because
of the hospital closure, and more than 90 percent felt it had substantially
impaired the community's economy.
PMID- 10183523
TI - Inspector General v. Hanlester Network: a new fraud and abuse standard?
PMID- 10183524
TI - Dinkins seeks thorough review of care provided by city's HHC.
PMID- 10183525
TI - The importance of street drug terms as diagnostic clues.
AB - "Words are both better and worse than thoughts; they express them and add to
them" [Tyrone Edwards]. Choice of street terms is a clinical expression of the
mental state and the drug history of the individual which evolves from repetition
and frequent use. Broadened experiences usually accompany continued use,
including experimentation with esoteric and powerful drug combinations. Drug
terms employed by the user may have diagnostic utility for the experienced
clinician in determining severity of symptoms. Recommendations for relapse
prevention become more credible through a familiar lexicon. Practitioner
understanding of drug terms as a tool to elicit information may lead to a deeper
understanding of the breadth and depth of patient use of drugs. The authors
recognize that they have contributed to the homogeneity, understanding, and
distribution of terms by this article.
PMID- 10183526
TI - Elderly care policy, formal and informal care. The Swedish case.
AB - This paper discusses the consequences of a 'greying' Sweden with respect to the
present Swedish policy for the care of the elderly and the role of the family as
care provider for the elderly. The present system of elderly welfare is
questioned, based on demographic facts, a review of the service systems and
research findings. The tentative conclusions are two-fold. Firstly, present
trends point to a shift in the Swedish welfare model, from a publicly financed
and run elderly care system to a mixed model based on public, private and
voluntary resources. Secondly, the fact that the informal care system functions
as the main provider of services for the elderly, means that the development and
implementation of support programmes for the family caregivers is of crucial
importance for the future. The challenge for the 1990s, then, is to improve
conditions for informal carers in order to enlarge the caring capacity of the
community.
PMID- 10183528
TI - District of Columbia regulations broadening scope of CON law upheld.
PMID- 10183527
TI - Terminated radiologist entitled to a hearing.
PMID- 10183529
TI - Purchase of lithotripter requires CON when used for services other than
originally stated purpose.
PMID- 10183530
TI - Male physician showing pay differential established prima facie case under Equal
Pay Act.
PMID- 10183531
TI - No duty to admit emergency patient when intensive care unit is full.
PMID- 10183533
TI - Physicians need not "agree" to refer business to violate anti-kickback statute.
PMID- 10183532
TI - Discharge of employee opposing lawful withdrawal of nutrition and hydration
upheld.
PMID- 10183534
TI - Blood bank held to reasonably prudent standard of care, not industry standard.
PMID- 10183535
TI - No private cause of action for suspended physician under Health Care Quality
Improvement Act.
PMID- 10183536
TI - Sanctions imposed for abuse of judicial system in staff privileges dispute.
PMID- 10183537
TI - Battery claim allowed for alleged failure to use family-donated blood.
PMID- 10183538
TI - Patient may not be moved to state with more liberal withdrawal of treatment laws
unless best interest established.
PMID- 10183539
TI - Wrongful life suit settled in Cincinnati.
PMID- 10183540
TI - California HIV confidentiality code prevents deposition of blood donors.
PMID- 10183541
TI - Epileptic food service worker is member of protected class.
PMID- 10183542
TI - Handbook disclaimer precludes finding of contractual relationship.
PMID- 10183543
TI - Infectious hospital waste constitutes hazardous waste.
PMID- 10183544
TI - Reasonable person standard not applicable in Pennsylvania informed consent cases.
PMID- 10183545
TI - Limit on damages in malpractice claim unconstitutional.
PMID- 10183546
TI - Change in Medicaid reimbursement policy for nonemergency claims requires adequate
notice.
PMID- 10183547
TI - Private right of action exists against state but not federal government to
enforce compliance with Medicaid Act.
PMID- 10183548
TI - Suicidal ideation constitutes emergency condition permitting indigency
application after treatment.
PMID- 10183550
TI - Hospital's risk management memorandum privileged.
PMID- 10183549
TI - Court denies motion to compel discovery where documents are "predecisional" or
"deliberative.".
PMID- 10183551
TI - Discovery rule for statute of limitations applies AIDS action.
PMID- 10183552
TI - Church affiliated medical center not exempt from state unemployment tax.
PMID- 10183553
TI - Fourth Circuit holds hospitals and their medical staffs lack capacity to conspire
during peer review.
PMID- 10183554
TI - CEO says despite costs, quality programs mean cost efficiency.
PMID- 10183555
TI - Pennsylvania hospitals make advances on several fronts in property tax battles.
PMID- 10183556
TI - Intracorporate Immunity Doctrine protects peer review.
PMID- 10183557
TI - Today's NHS. Good for people's bodies and minds.
AB - The Institute of Health Services Management met in Brighton in June to discuss
the burning topics of the NHS today. The following four articles are based on
papers presented at that conference. Here, Secretary of State William Waldegrave
reasserts the founding principles of the NHS, while justifying the basic reasons
for the reforms.
PMID- 10183558
TI - Another Pyrrhic victory.
PMID- 10183559
TI - The Air Medical Reimbursement Congress: a report of the proceedings.
PMID- 10183561
TI - No certificate of need required for additional operating room.
PMID- 10183560
TI - Federal antitrust jurisdiction in peer review cases: the Pinhas decision.
AB - In Summit Health Ltd. v. Pinhas, the United States Supreme Court by a narrow
majority found that the exclusion of an ophthalmologist from a hospital in Los
Angeles had a sufficient effect on interstate commerce to establish federal
jurisdiction under the Sherman Act. In resolving a split among the federal
circuit courts of appeal, the Court applied the broad jurisdictional test from
McLain v. Real Estate Board of New Orleans, Inc. to peer review proceedings.
Despite many ambiguities in the majority opinion by Justice Stevens and a
scathing dissent by Justice Scalia, the effect of Pinhas will be to increase the
suits in federal court on antitrust grounds brought by aggrieved medical staff
members and applicants denied appointments or privileges, and to decrease, if not
eliminate, the likelihood of preliminary dismissal on jurisdictional grounds.
This, in turn, should serve to emphasize the importance of complying with the
Health Care Quality Improvement Act in order to obtain immunity from damages
under federal antitrust and state laws.
PMID- 10183562
TI - Bed need formula creates presumption of sufficient beds.
PMID- 10183563
TI - Parent not liable for child's hospital bills unless aware of hospital's
expectations of payment.
PMID- 10183564
TI - Clear language of promise in employee handbook must be cited to establish
employment contract.
PMID- 10183565
TI - Court upholds hospital's drug testing program.
PMID- 10183566
TI - Suit allowed for receipt of HIV infected blood at military hospital.
PMID- 10183567
TI - Independent judgment of LPN required for "supervisor" exemption.
PMID- 10183568
TI - Civil penalties available for patient dumping.
PMID- 10183569
TI - State mental hospital patients not entitled to compensation for work.
PMID- 10183570
TI - No hospital duty to surrogate test blood received from blood center.
PMID- 10183571
TI - No special reimbursement for expenses related to nursing shortage.
PMID- 10183572
TI - HHS' indigency determination regulation upheld.
PMID- 10183573
TI - No due process right in private hospital privileges revocation.
PMID- 10183575
TI - Costs--what you need to know.
PMID- 10183574
TI - Disruptive conduct grounds for revoking staff privileges.
PMID- 10183576
TI - The definition of a clinical engineer.
AB - The American College of Clinical Engineering formed a committee to develop a
contemporary definition of a Clinical Engineer. The committee considered existing
definitions including that currently used by the Clinical Engineering Board of
Examiners of the International Certification Commission. Educators and other
societies provided other definitions. Following substantial discussion and
revisions, the definition was adopted by the Board of Directors of the ACCE on
May 13, 1991.
PMID- 10183577
TI - Rosenblit v. Fountain Valley Regional Hospital & Medical Center: physician fair
hearing rights enforced at last.
PMID- 10183578
TI - Evidence must back suspected impairment.
PMID- 10183579
TI - A new system for understanding mechanical ventilators.
PMID- 10183580
TI - Requirements for protection against ionizing radiation from nuclear materials.
PMID- 10183581
TI - Labels.
AB - As pediatric care becomes more complex and technical, there is a continuing
tendency among health care professionals from all fields to use labels, jargon,
and abbreviations when talking about and talking to young patients. This article
offers possible explanations for the use of labels and jargon, and provides a
summary of the dangers inherent in this sort of communication. Simple suggestions
for alternative forms of communication are provided.
PMID- 10183582
TI - Beyond honesty: choosing language for talking to children about pain and
procedures.
AB - Gene Stanford, long an influential and colorful member of the Association for the
Care of Children's Health (ACCH), died on February 25, 1991, after a long
illness. His presentation, "Talking to Children about Medical Procedures," at the
1985 ACCH conference in Boston was heard by and has influenced the thinking and
clinical skills of many ACCH members. As an author and coauthor of many
publications addressing communication skills and the needs of children in health
care, it is fitting that his memorable presentation in 1985 incorporated both
areas of Gene's expertise. At my request, an outline was submitted for this theme
issue. Unfortunately, he was not able to develop it further. However, it is
highly informative, useful, and representative of quality clinical skills and
judgment just the way it is. For this reason, it is printed here just as Gene
wrote it. It is a small piece of the legacy that Gene leaves behind for children
and families in health care.
PMID- 10183583
TI - Bishops and healthcare leaders explore ministry issues together.
PMID- 10183584
TI - Strategic planning for long-term care providers.
PMID- 10183585
TI - Public policy requires imposing sanctions on incompetent physician.
PMID- 10183586
TI - Peer review materials discoverable in antitrust action.
PMID- 10183587
TI - Failure to reveal material risks of surgery including surgeon's alcoholism
vitiates informed consent.
PMID- 10183588
TI - License probation is basis for suspension of privileges.
PMID- 10183589
TI - Blood bank is health care provider protected by medical malpractice statute of
limitations.
PMID- 10183590
TI - Not-for-profit hospital tax exempt as of its first day of operation.
PMID- 10183591
TI - Wrongful death claim against blood bank united in interest with hospital not
barred by statute of limitations.
PMID- 10183592
TI - Zoning regulations inapplicable to drug treatment facility.
PMID- 10183593
TI - Physicians and hospitals: new pressures on the partnership.
PMID- 10183594
TI - Joint Commission's quality focus is on improving systems.
PMID- 10183595
TI - Expiration dates, damp dusting are sent out to pasture.
PMID- 10183596
TI - The emergence of maternal-fetal conflict policies.
AB - George Washington University Medical Center's Policy on decisionmaking by
pregnant patients is being widely circulated by the ACLU; copies of the Policy
can be obtained by calling the American Civil Liberties Union Reproductive
Freedom Project. There is, of course, much disagreement over the details of the
Policy; not everyone will agree with its underlying philosophy favoring maternal
rights. Nevertheless, there does seem to be a consensus that wherever possible
these conflicts should be resolved in accordance with previously adopted policies
rather than by the courts on an ad hoc basis. Had the Policy been in place in
1987, the Carder case would probably not have been submitted to a judge in the
first place, nor would Angela Carder have been forced to undergo a Caesarean
section. All hospitals should consider adopting a maternal-fetal conflict policy,
and those that do so should be aware of the George Washington University Medical
Center Policy, whether or not they agree with its provisions. Whatever policy
each hospital ultimately develops should be integrated with decisionmaking and
informed consent policies already in place. The formulation and implementation of
such a policy, reflecting the hospital's legal and ethical obligations to its
pregnant patients, will go a long way towards preventing unnecessary resort to
the courts.
PMID- 10183597
TI - Conn. hospital's conduct violated labor law--court.
AB - A federal appeals court in New York has ruled that Waterbury (Conn.) Hospital
violated federal labor law in 1986 when it hired replacement nurses rather than
returning striking nurses to fill certain hospital jobs. The court said the
hospital didn't meet all the conditions under which it is allowable to hire
permanent replacements during a strike.
PMID- 10183599
TI - Clinical societies exchange views on complex ethical issues.
PMID- 10183598
TI - Moral ordering in deliberations of ethics committees examined.
PMID- 10183600
TI - Cogeneration and environmental responsibility at Rhode Island Hospital.
PMID- 10183601
TI - Refined imaging technologies spark urgent interest.
AB - On assignment for Computers in Healthcare, imaging technology consultant Deborah
Kohn scoured the exhibit hall at the huge Association for Information and Image
Management (AIIM) annual conference--this year boasting 33,500 attendees--where
she discovered that a five-year hesitancy about image management is definitely
over. Across all industries, and particularly in healthcare, image management
technologies are booming.
PMID- 10183602
TI - A revealing look at the realities of reform.
AB - Attendees of ASIM's 35th Annual Meeting in Washington heard first hand from two
leading health policy figures--Gail Wilensky and Sen. Jay Rockefeller--about
what's ahead for health care reform. Vermont Gov. Howard Dean, MD, an internist,
looked at the roles that states--and physicians--can take.
PMID- 10183603
TI - Is America ready for an all-payer system?
AB - Three panelists at the featured plenary session--Uwe Reinhardt, PhD, Richard
Kronick, PhD, and Ronald Rouse--examined whether health policy-makers and the
public are prepared to consider an all-payer system as a way to reform the
American health care system.
PMID- 10183604
TI - How will private insurers use the RBRVS?
PMID- 10183605
TI - Health care mergers and acquisitions: structuring the transaction.
PMID- 10183606
TI - Bankrupt hospital can't lie to hospital union.
PMID- 10183607
TI - For-profit hospital finds it can't beat City Hall--that is, the financing deal
offered by the city.
AB - American International Hospital in Zion, Ill., doesn't lack support from city
hall. In an unusual transaction for an investor-owned hospital, the city recently
sold $20 million in taxable debt for the purpose of lending the proceeds to the
hospital to help finance a replacement facility. The deal saved the hospital, the
area's largest employer, as much as 2.5 percentage points on the interest rate.
PMID- 10183608
TI - Discharge planning: envisioning the future.
PMID- 10183609
TI - Value questionnaire: a patient-care tool.
PMID- 10183610
TI - Creativity and innovation.
PMID- 10183611
TI - Exclusion of hospitals from participation in preferred provider network upheld by
court.
PMID- 10183612
TI - Physician's chronic alcohol abuse ruled material risk by Louisiana court.
PMID- 10183613
TI - Statute protecting peer review records: a double-edged sword?
PMID- 10183614
TI - The changing definition of AIDS. What's in a name?
AB - Earlier this year, the U.S. Centers for Disease Control proposed altering its
definition of acquired immune deficiency syndrome (AIDS) to include those with
200 or fewer CD4 cells. That proposal, scheduled to take effect April 1, 1992,
would dramatically increase the number of Americans officially considered as
having AIDS. The previous definition relied on a list of specific opportunistic
infections, tumors, or itemized manifestations of HIV disease. While eventually
the definition of AIDS should be replaced with a definition of HIV disease--which
would include all those who are infected with the human immunodeficiency virus-
the CDC proposal would be a useful stopgap measure. It would provide access to
needed treatments such as AZT to thousands of men and women who now are excluded
from reimbursement systems including private health insurance and Medicaid.
PMID- 10183615
TI - Computer-based record emerges in radiology.
PMID- 10183616
TI - AIDS placement: who needs what kind?
PMID- 10183617
TI - Look-alike and sound-alike drug names: the problem and the solution.
AB - This list of 645 pairs of look-alike and sound-alike drug names (1,290 names are
shown; they are listed both ways), has been complied to graphically emphasize the
importance for the pharmaceutical industry, the United States Adopted Name (USAN)
Council, and Food and Drug Administration (FDA) to select new names with great
care. It also stresses to health professionals the necessity of writing legibly,
writing complete orders, speaking slowly and clearly when giving verbal orders,
carefully reading prescription orders, knowing what is wrong with patients,
maintaining records of previous drugs patients have received, and learning about
new drug products. It also indicates that patients must be educated about the
medications they are taking. Your cooperation in alerting the authors of names
they may have overlooked or of new problems would be greatly appreciated. When a
sufficient number of additions are received, an updated list will be published.
PMID- 10183618
TI - AHA meeting focuses on reform.
PMID- 10183620
TI - Role of the National Interim Provider Board.
PMID- 10183619
TI - What's in a name? Child life and the play lady legacy.
AB - Child life specialists can now earn a nationally recognized credential as a
"Certified Child Life Specialist" from the Child Life Certifying Commission. Yet,
uncertainties linger about the nature of the child life specialist's identity,
roles, and status among health care professionals. This article highlights the
historical contexts within which a series of significant changes occurred in the
profession's name. How Emma Plank and Thesi Bergmann, two pioneering authors in
the field, influenced and were influenced by the play lady legacy is shown, and
recommendations are made to find ways to honor the profession's past, while
addressing the challenges of the 1990s.
PMID- 10183621
TI - What keeps people well? A new paradigm for pastoral care.
PMID- 10183622
TI - The trials of no-transport.
PMID- 10183623
TI - How four health-care gurus would change American medicine.
PMID- 10183624
TI - Inspector General wins round two of Hanlester Case.
AB - The decision of the HHS Departmental Appeals Board Appellate Division in
Inspector General v. Hanlester Network provides guidance as to the aspects of
joint ventures that pose fraud and abuse concerns by listing the factors that may
indicate an improper purpose. Together with the fraud and abuse safe harbors, the
decision helps identify the pitfalls associated with physician investment in
suspect joint ventures. This article analyzes the latest Hanlester decision,
forecasts the future of joint venturing after Hanlester and the safe harbors, and
offers some guidance to potential investors in light of these developments.
PMID- 10183626
TI - The "dirty words" of antitrust.
PMID- 10183625
TI - Lewisburg Community Hospital v. Alfredson: does restriction of privileges without
due process violate medical staff bylaws?
PMID- 10183627
TI - Gaining wisdom through clinical costing: clinical resource management. Conference
conducted by the Health Services Administration Research Unit, Monash Medical
Centre.
PMID- 10183628
TI - Standardized laboratory test name nomenclature: a requirement for data base
exchange.
AB - A new, comprehensive, computer-based medical nomenclature is briefly described in
this paper. The terms of this nomenclature are organized into a single hierarchy.
Laboratory test names have been made an integral part of the nomenclature,
applying classification rules the same way as in the rest of the hierarchical
tree.
PMID- 10183629
TI - Pinhas lessons.
PMID- 10183630
TI - Revisiting the three-legged stool: striking a new balance among trustees,
administrators, and physicians. Report of forum held in Durham, North Carolina,
May 17-19, 1990.
PMID- 10183631
TI - The classification of home health care nursing diagnoses and interventions.
PMID- 10183632
TI - Provoking passion and prescriptions.
PMID- 10183633
TI - Experimental definition in Adams leads to controversy.
PMID- 10183634
TI - Decoding research terminology.
PMID- 10183635
TI - Looking beyond the gadgets to the future of ambulances.
PMID- 10183636
TI - An ageing population: a positive spur to improved health care?
PMID- 10183637
TI - Cultural competence in the care of elderly Chinese persons in New York City: a
symposium. Proceedings of the PRIDE Conference of June 11, 1991.
PMID- 10183638
TI - Quality improvement initiative report.
PMID- 10183640
TI - Application of artificial intelligence to pharmacy and medicine.
AB - Artificial intelligence (AI) is a branch of computer science dealing with solving
problems using symbolic programming. It has evolved into a problem solving
science with applications in business, engineering, and health care. One
application of AI is expert system development. An expert system consists of a
knowledge base and inference engine, coupled with a user interface. A crucial
aspect of expert system development is knowledge acquisition and implementing
computable ways to solve problems. There have been several expert systems
developed in medicine to assist physicians with medical diagnosis. Recently,
several programs focusing on drug therapy have been described. They provide
guidance on drug interactions, drug therapy monitoring, and drug formulary
selection. There are many aspects of pharmacy that AI can have an impact on and
the reader is challenged to consider these possibilities because they may some
day become a reality in pharmacy.
PMID- 10183639
TI - Graduate nursing students' attitudes toward gay and hemophiliac men with AIDS.
AB - Subjects were 180 registered nurses enrolled in a master's nursing program. By
random assignment, each read one of six versions of a vignette about a male
patient. Vignettes differed in terms of patient's diagnosis (AIDS of unspecified
origin, AIDS in a hemophiliac infected by blood transfusion, and leukemia) and
sexual preference (gay or heterosexual). Nurses evaluated the patient on two
scales, one involving judgments of patients and the other concerning willingness
to interact socially with them. The hemophiliac/AIDS and leukemia patients were
judged significantly less responsible for and less deserving of their illnesses
than was the patient with AIDS of unspecified origin (p less than .001). However,
all three diagnostic categories were considered equally deserving of the best
possible care. Both categories of AIDS patients were stigmatized in terms of
certain social interactions. There was also some weak evidence of antigay bias.
Implications for theory and practice are discussed.
PMID- 10183641
TI - Third decision in the Hanlester Case creates further uncertainty.
PMID- 10183642
TI - Battery claim of Jehovah's Witness rejected by Michigan court.
PMID- 10183643
TI - Radiology reports in the cross fire.
PMID- 10183644
TI - Hanlester Laboratories decision: how is it affected by new sanctions and
penalties regulations?
AB - The following excerpts from the briefs recently submitted to Administrative Law
Judge (ALJ) Stephen Kessel in the Hanlester Laboratories administrative
proceeding, deal with the applicability of a January 29, 1992 final rule on fraud
and abuse sanctions and civil money penalties (57 Fed. Reg. 3,298 (January 29,
1992) to the case. Counsel for Hanlester Laboratories, Patric Hooper and W.
Bradley Tully of Hooper, Lundy & Bookman, Inc. in Los Angeles, argue that the
Office of the Inspector General (OIG-HHS) is trying to change the rules "well
after the game has been played," and that this "is obviously being done for the
sole purpose of negating the rights" of the Hanlester respondents. The Office of
the General Counsel (OGC), in a brief prepared by OGC attorney Larry J. Goldberg,
contends that ALJ Kessel "must apply these regulations in rendering his
decision," arguing that the "regulations at issue do not even involve a change in
policy, but merely a clarification." The Hanlester case (The Inspector General v.
Hanlester Network et al., No. C-448 (Department of Health and Human Services,
Departmental Appeals Board, Civil Remedies Division) was remanded by the
Departmental Appeals Board to ALJ Kessel on September 18, 1991. It is the first
case to consider the application of the antikickback statute to a joint venture,
and is the first HHS civil exclusion case to be brought as the result of
allegations of violations of the antikickback statute (see HealthSpan, November
1991, p. 8).
PMID- 10183645
TI - Court rejects contributory negligence defense in hospital liability case.
PMID- 10183646
TI - Ex parte contacts between plaintiff's physician and defense attorneys: protecting
the patient-litigant's right to a fair trial.
PMID- 10183647
TI - Building organizational leadership.
PMID- 10183648
TI - World of computers.
AB - Being well informed on the latest computer terminology is a continuous challenge
these days. In this article Pinkert and Wear give us a vocabulary lesson for
computer consumers.
PMID- 10183649
TI - The city of Birmingham's wellness partnership contains medical costs.
PMID- 10183650
TI - Heeding patient's directive essential.
PMID- 10183651
TI - Legal advice for the contracting physician.
PMID- 10183652
TI - Court rules public policy bars discovery of peer review material and deposing of
participants.
PMID- 10183653
TI - Hospitals with TQM offer good value to payers.
PMID- 10183654
TI - How to speak "finance". A primer for the non-financial manager.
PMID- 10183656
TI - Special report on taxation. Court of Appeals denies tax exemption based on
"substantial commercial purpose".
AB - When viewed against the background of continuing state and federal legislative
efforts to limit the availability of tax-exempt status, the Living Faith case
could be seen as yet another indication of difficult times ahead for nonprofit
providers. Although it is too early to tell whether this will in fact be the
case, tax-exempt providers should be aware of the Living Faith case as perhaps
the clearest statement from a federal appeals court in recent years that the
operation of an enterprise in too businesslike a manner may make it a taxable
activity. Tax-exempt providers that now operate or plan to operate ancillary
businesses, whether through joint ventures, wholly-owned subsidiaries, or
otherwise, should carefully evaluate such activities against the criteria
articulated in Living Faith. This analysis is important not only for purposes of
determining whether such activities can qualify for tax-exempt status in and of
themselves, but also as an indicator of how such activities might affect the tax
exempt status of the provider.
PMID- 10183657
TI - Why surgeons should work with their Medicare carriers: the medical director's
view.
PMID- 10183655
TI - Union organizing drives dealt a blow by Supreme Court.
AB - The Lechmere case is important because it reaffirms that employers' property
rights take precedence over the rights of nonemployees to engage in union
organizing on employers' property. This is particularly important for hospitals
and health care institutions because of their heightened exposure to union
organizing activity after American Hospital Association v. National Labor
Relations Board, discussed above. Providers should, however, remember two points.
First, the principal focus of Lechmere was on union organizing by nonemployees;
nothing in Lechmere limited the basic right of employees to form and join labor
unions as guaranteed by Section 7 of the NLRA. Additionally, Lechmere
notwithstanding, providers must be careful not to discriminate in their approach
to union organizing activities--even by nonemployees. Thus, if a provider allows
nonemployee groups other than unions to enter upon its property for purposes of
soliciting employees and/or distributing literature, any attempt to bar
nonemployee union organizers from the property would probably be deemed
discriminatory and could indeed be an unfair labor practice. (In Lechmere, the
employer consistently enforced a ban against all such nonemployee groups.)
PMID- 10183658
TI - Considering family members' rights in health care decisions.
PMID- 10183659
TI - Lab-related findings from the Sixth International Conference on AIDS.
PMID- 10183660
TI - The Air Medical Reimbursement Congress.
PMID- 10183661
TI - Competitors can take advantage of certificate of need proceedings, rules 9th
Circuit.
PMID- 10183662
TI - Forging new, innovative relationships.
PMID- 10183663
TI - Physician's recovery of $150,000 from hospital upheld.
PMID- 10183664
TI - Medical computing standards ASTM (American Society for Testing and Materials)
Committee E-31. A review of published standards and current projects February,
1992.
AB - This document describes the activities of ASTM Committee E-31 in the area of
standards for computer systems in medical applications. Some of these efforts
have already culminated in published standards, some are well along in the
development process, and some are just getting started.
PMID- 10183665
TI - Living tissue and organ donors and property law: more on Moore.
PMID- 10183666
TI - The sound may be sweeter by another name.
AB - A name change from "facilities management" to "outsourcing" could spur new
interest in a concept once shunned by most of the healthcare information systems
industry. Big-name contracts are legitimizing such arrangements, opening fresh
avenues for organizations requiring flexible I/S services.
PMID- 10183668
TI - Strategies for building, improving hospital/physician relationships.
PMID- 10183669
TI - Debate will attempt to define future effects of managed care.
PMID- 10183671
TI - Mission and ethics enter into decisions on medical resources.
PMID- 10183670
TI - Hospital leadership must be set up to steer, not just row.
PMID- 10183672
TI - Patient-centered care plan gets departments working together.
PMID- 10183667
TI - Some collaboration required: can hospitals break the barriers?
PMID- 10183674
TI - Keeping your hospital's focus centered on the community.
PMID- 10183673
TI - To influence reform, team up with non-provider interests.
PMID- 10183675
TI - Strategic planning provides direction.
AB - Dr. Tom Regan, professor of sociology and hospital trustee, discusses the role
and preparation of hospital board members and their influence on Canadian health
care directions.
PMID- 10183677
TI - Putting HCQIA (Health Care Quality Improvement Act of 1986) to the test.
PMID- 10183679
TI - Legislative forum: focus on long-term care.
PMID- 10183678
TI - Hanlester Laboratories decision gives dangerously broad interpretation of federal
anti-kickback statute.
PMID- 10183676
TI - In sight: a vision for a healthy America. The 77th Annual Catholic Health
Assembly, June 14-17, Anaheim, California.
PMID- 10183682
TI - Implementing healthcare reform: who, how, and when.
PMID- 10183681
TI - The "Oregon Plan": a symposium. Cleveland Conference on Bioethics, June 3-5,
1990.
PMID- 10183680
TI - Better quality, better health. IHSM annual conference.
PMID- 10183683
TI - Effectiveness, efficiency, excellence: can they coexist in health care?
AB - The conference certainly provided a great deal of food-for-thought for
participants. From the imperatives of funding restraint, presented by Dr Scully
and Professor Manga, to the public attitudes and opinions research presented by
Allan Gregg and the anticipated public policy initiatives presented by Senator
Kirby, the audience was challenged to take a new look at health care. Chief Ovide
Mercredi presented a very earnest plea on behalf of the aboriginal people of
Canada for restoration of their dignity and self-determination, as a key to
better mental and physical health. The message to health care leaders was that
quality improvement not only works, but also leads to more efficient use of
resources. Dr Donald Berwick blew away the myths that often prevent organizations
from establishing quality improvement programs and presented a blueprint for
success. Other speakers gave examples of successful QI programs they were
personally involved in. One of the most interesting presentations was Dr Naylor's
able exposition of the role of research in assuring quality. This must have
opened many eyes to how resources can be used without real benefit to patients,
when proper outcome measurement is not used. Indeed, outcome measures may be an
important key to dealing with some of the problems facing health care.
PMID- 10183684
TI - Visionary qualities a must, say conference keynoters.
PMID- 10183686
TI - All talk and no action. Information systems users face regulatory challenges.
PMID- 10183685
TI - Taking it from the top. Strengthening the executive information team.
PMID- 10183687
TI - Quality care on a budget. Realizing benefits from clinical systems.
PMID- 10183688
TI - Court awards attorney's fees and costs under HCQIA.
PMID- 10183689
TI - Indiana court examines standard of care for graduate medical trainees.
PMID- 10183691
TI - Physician fails to establish breach of contract by hospital.
PMID- 10183690
TI - Court rulings favor health care provider over insurer.
PMID- 10183692
TI - Use of catheter recalled by manufacturer leads to hospital liability.
PMID- 10183693
TI - Executive forum on information management.
PMID- 10183694
TI - Ethics in healthcare.
PMID- 10183695
TI - Low power laser protocols and the FDA.
PMID- 10183696
TI - Gd-DTPA enhances uses for MR imaging of body.
PMID- 10183697
TI - Endovaginal ultrasound abets fetal assessment.
PMID- 10183698
TI - Nonionic contrast media open new paths for MRI.
PMID- 10183699
TI - Ultrasound not yet ripe for prostate screening.
PMID- 10183700
TI - IVUS shows thickness of cardiac vessel walls.
PMID- 10183701
TI - PET replaces thallium for some cardiologists.
PMID- 10183702
TI - The pulse oximeter guide: a basic guide to the use and purchase of pulse
oximeters.
PMID- 10183704
TI - MR effective at detecting pathology of marrow space.
PMID- 10183703
TI - Integrated information management system.
AB - This article presents the concepts of a computerized information system and its
potential applications to Emergency Medical Services (EMS). It is an
informational article intended to provide administrators clear concepts of how
computers may be best used to provide information in integrated networked systems
for EMS needs. It addresses the function of a system, processes of computerizing
a department, planning, and provides an overview of computer hardware.
PMID- 10183705
TI - MRI best modality for neuroimaging of AIDS.
PMID- 10183706
TI - MR depicts perfusion of brain and heart.
PMID- 10183707
TI - Consensus emerging in salivary gland imaging.
PMID- 10183708
TI - MRI assists diagnosis of inflammatory joint disease.
PMID- 10183709
TI - Enhanced resolution of pituitary fossa by three-dimensional fat-suppressed
gradient-echo magnetic resonance: before and after gadolinium enhancement.
AB - In imaging small anatomical parts such as the pituitary fossa, thin sections
enhance the spatial resolution. Gradient recalled images (GRASS) using three
dimensional volume data produce ultrathin contiguous sections with a high signal
to-noise ratio. In this study, conventional spin-echo magnetic resonance images
(MRIs) of the pituitary fossa were compared to three-dimensional gradient
recalled MRI in 5 volunteers and 10 patients suspected of having pituitary gland
abnormalities. Utility of fat suppression was also assessed, along with
gadolinium enhancement. Conventional spin-echo and three-dimensional spoiled
GRASS images, three-dimensional spoiled GRASS images without and with fat
suppression (Group II), and three-dimensional spoiled GRASS images with fat
suppression before and after gadolinium enhancement were compared. Three
dimensional spoiled GRASS images provided better delineation of the pituitary
fossa structures. There was differential enhancement between the normal gland
and pituitary tumors. The fat suppression technique following gadolinium
administration helped separate the high signal of tumor from the high signal of
the clivus marrow. In conclusion, T1-weighted three dimensional gradient-echo
images with fat suppression following gadolinium enhancement appear promising in
evaluation.
PMID- 10183710
TI - Fast spin-echo, MRA alter disease diagnosis.
PMID- 10183711
TI - Enhanced MRI fills in soft tissue features.
PMID- 10183713
TI - MRI users brace for discord over contrast.
PMID- 10183714
TI - PET's metabolic potency wins it clinical respect.
PMID- 10183712
TI - Fight against restenosis has many active fronts.
PMID- 10183715
TI - Breast MR finds role as pretreatment test.
PMID- 10183716
TI - Fourth Global Congress on Patient Cards & Computerisation of Health Records,
Berlin, Germany 25-28 May, 1992.
PMID- 10183717
TI - EPINet: a computerized blood and body fluid exposure reporting system from Dr.
Janine Jagger.
PMID- 10183718
TI - Purposes and principles of staging.
PMID- 10183719
TI - Naming what we do--nursing vocabularies and databases.
PMID- 10183720
TI - Ninth Circuit establishes Federal rule regarding coordination of insurance
benefits.
PMID- 10183721
TI - Patient's constitutional rights do not include the right to an assisted suicide
for cryogenic preservation.
PMID- 10183722
TI - Court invalidates Medicare GME reaudit regulation. Methodist Hospitals of Memphis
v. Sullivan.
PMID- 10183723
TI - Planned Parenthood v. Casey. Eroding access to reproductive services.
PMID- 10183724
TI - 3rd Circuit keeps split alive on autologous bone marrow transplants for breast
cancer. Clark v. K-Mart Corporation.
PMID- 10183725
TI - Federal District Court rejects all claims by aggrieved physician. Stitzell v.
York Memorial Osteopathic Hospital.
PMID- 10183726
TI - Provider's waiver of copayment allows health insurer to avoid all payment.
Kennedy v. Connecticut General Life Insurance Co.
PMID- 10183727
TI - Substantial punitive damages award upheld on appeal. American Medical
International, Inc. v. Scheller.
PMID- 10183728
TI - Convention launched with building demolition.
PMID- 10183729
TI - The Society for Academic Emergency Medicine focuses on prehospital care.
PMID- 10183730
TI - When is drug testing a reasonable search? Kemp v Claiborne County Hospital.
PMID- 10183731
TI - Technical description and classification of modes of ventilator operation.
AB - These changes are proposed as a starting point for the more logical application
of ventilator terminology and are for your consideration and debate. It is our
contention that this system can be easily adopted once the basics of the
classification system are understood.
PMID- 10183732
TI - Court rules that care cannot be withdrawn where parents disagree on treatment
plan. In re: Jane Doe, A Minor, Civil Action No. D-93064, Superior Court of
Fulton County, GA.
PMID- 10183734
TI - Hospital acted properly in suspending surgical privileges of physician with AIDS.
Estate of Behringer v. Medical Center at Princeton.
PMID- 10183733
TI - Supreme Court preserves right to abortion, but allows restrictions. Planned
Parenthood of Southeastern Pennsylvania v. Casey.
PMID- 10183735
TI - Out-of-laboratory testing. Conference held in Ottawa, Ontario, April 30-May 2,
1992, sponsored by the Canadian Society of Clinical Chemists, the Intersociety
Council of Laboratory Medicine of Canada, and the Federal Bureau of Radiation and
Medical Devices.
PMID- 10183736
TI - Naming and framing occupational therapy: a lecture dedicated to the life of Nancy
B.
AB - The case of Nancy B. is testimony to the importance of occupation to living and
hence the importance of occupational therapy. Yet the importance of the
discipline is poorly recognized. It is argued that the failure of occupational
therapy to gain wide recognition is due to a problem in communicating its
importance simply, easily and clearly and that the discipline needs to be named
and framed in positive and powerful terms. The values on which to base this
naming and framing are articulated. Based on the Occupational Therapy Values
Statement, it is proposed that the discipline be framed in an Enablement Model
and that, accordingly, occupational therapy be described as the discipline
concerned with enabling occupational competence guided by an understanding of the
individual, the environment and their interaction in determining occupational
competence.
PMID- 10183737
TI - Cost of treatment outcomes: a meeting sponsored by The Managed Health Care
Congress Northeast--New York.
PMID- 10183739
TI - EMS administrators armed at EMS law and policy.
PMID- 10183738
TI - ERISA loophole permits utilization review firms to avoid liability for
malpractice. Corcoran v. United Healthcare, Inc.
PMID- 10183742
TI - How much protection is enough? Debate over consumer safeguards in LTC insurance
intensifies. Panel discussion.
AB - The growing momentum behind a push for federal intervention in regulating long
term care insurance has sparked a tempestuous controversy with insurers,
politicians, consumers and regulators in the eye of the storm. Some insurers are
adamantly opposed to nationwide standards, while others have banded together to
lobby for a combination of federal/state oversight. Consumer representatives
generally favor uniform regulation, but regulators and politicians are split on
the issue of whether the states or feds should control the requirements. A panel
representing the assorted views of the special interest groups with a stake in
this debate shared their perspectives during the Eighth Annual Private Long Term
Care Insurance Conference that recently convened in San Francisco. The following
comments are excerpts from their discussion on the role of regulation in consumer
protection.
PMID- 10183740
TI - Scientific world belatedly recognizes HIV risks to laboratorians.
PMID- 10183741
TI - A reply to "Lewisburg Community Hospital v. Alfredson: does restriction of
privileges without due process violate medical staff bylaws?".
PMID- 10183743
TI - Monitoring the exercise of clinical privileges. Havens v. Tomball Community
Hospital.
PMID- 10183744
TI - Whither health care reform? A roundtable.
PMID- 10183747
TI - California case could raise COBRA costs. Coble v. Bonita House, Inc.
PMID- 10183745
TI - Notes from the National Conference on Prevention of Device-mediated Bloodborne
Infections.
PMID- 10183748
TI - Proactive healthcare organizations strengthen key relationships.
PMID- 10183746
TI - A pocket full of change.
PMID- 10183749
TI - Mitchell: managed competition not a panacea.
PMID- 10183751
TI - Public accountability for trustees.
PMID- 10183750
TI - Systems, stress, and survival: psychiatric hospitals in the 1990s.
AB - Presented at the invitation of the President of the National Association of
Private Psychiatric Hospitals, January 30, 1991, Marco Island, Florida, this
paper is addressed to those whose interest in psychiatric hospitals centers
around quality-of-care issues and who today are concerned about the deleterious
impact of many forces upon the quality of hospital care. The author begins with
comments about systems under stress, then turn to the quality-of-care issues, and
end with some speculations about the future of psychiatric hospitals.
PMID- 10183752
TI - Health care reform could top Clinton's presidential agenda.
PMID- 10183753
TI - Speaker tries to make CQI easy; sees vital role for patient reps.
PMID- 10183754
TI - Surgical practice today. A young surgeon's viewpoint.
PMID- 10183755
TI - Presidential Address. Surgery is a great career.
PMID- 10183757
TI - Court upholds hospital that fired employee who refused drug test. Kemp v.
Clairborne County Hospital.
AB - An employee at 23-bed Claiborne County Hospital, Port Gibson, MS, who sued the
hospital after she was terminated for refusing to comply with the facility's drug
testing program, has lost her case, but the hospital is changing its testing
methods to avoid future problems. The testing procedure was initiated because the
hospital believed it had reasonable grounds to suspect that a mass drug test of
its employees would turn up evidence of work-related drug or alcohol use. The
test proved that a few hospital employees were using substances while working,
says Melvin H. McFatter, Port Gibson, the hospital's attorney. The employees were
given advance written notice of the date and place of the test. All employees
gave advance written consent to the test. Blood and urine samples were drawn.
PMID- 10183756
TI - Departmental appeals board issues final decision in Hanlester Network case.
PMID- 10183758
TI - Health reform: states take the lead, but....
PMID- 10183760
TI - President's Address. Planning new initiatives.
PMID- 10183761
TI - Inaugural address. Health care reform: let's get it done!
PMID- 10183759
TI - Reform: ethics and politics.
PMID- 10183762
TI - Health care costs take center stage.
PMID- 10183763
TI - Medicaid coverage of organ transplants: circuit split developing. Dexter v.
Kirschner.
PMID- 10183764
TI - Case conference--Ethical issues in long term care. Conference held at St.
Vincent's Hospital, New York, February 11, 1992.
PMID- 10183765
TI - Fact, fallacy and fairness: the ethics of health care reform.
PMID- 10183767
TI - Executive forum: how design affects productivity in settings where office-like
work is done.
PMID- 10183766
TI - Design technology: programming user needs.
PMID- 10183768
TI - Design technology: breaking the mold.
PMID- 10183769
TI - Design technology: psychoneuroimmunology.
PMID- 10183770
TI - Design technology: applied design research.
PMID- 10183771
TI - Design technology: color for healing.
PMID- 10183772
TI - Design technology: lighting for health.
PMID- 10183774
TI - Centers of excellence: theory & types.
PMID- 10183773
TI - Design technology: art for healthcare.
PMID- 10183776
TI - Centers of excellence: the Starbright Pavilion.
PMID- 10183777
TI - Executive forum: the Corinne Dolan Alzheimer Center.
PMID- 10183778
TI - Centers of excellence: new possibilities.
PMID- 10183779
TI - Healthcare design: lessons from abroad. Walter C. Mackenzie Health Sciences
Center.
PMID- 10183775
TI - Centers of excellence: Johns Hopkins ambulatory care building.
PMID- 10183780
TI - Healthcare design: lessons from abroad. In the U.K., small is beautiful.
PMID- 10183781
TI - Healthcare design: lessons from abroad. St. Mary's on the Isle of Wight.
PMID- 10183784
TI - Healthcare interior design scholarship awards. Bronx Lebanon Hospital; Arkansas
Children's Hospital.
PMID- 10183782
TI - Healthcare design: lessons from abroad. Future possibilities.
PMID- 10183785
TI - Healthcare environment awards. South Shore Hospital; Ottawa Civic Hospital.
PMID- 10183783
TI - Residential design: the new frontier in healthcare design.
PMID- 10183786
TI - Exemplary healthcare facilities.
AB - Symposium attendees had the opportunity to choose from 13 different tours
designed to meet their diverse needs. Each tour consisted of one or more
facilities grouped together to show innovative solutions to the problems in
healthcare design today. Tours were of exemplary healthcare facilities throughout
the Boston area, some of which were presented as case studies in the program.
Facility types included medical centers with special services, ambulatory care
centers, long term care facilities, pediatric hospitals, a school and center for
the blind, a hospice, research and educational facilities, a community health
center, an AIDS respite project, and a Ronald McDonald house.
PMID- 10183787
TI - Executive forum: the future of healthcare.
PMID- 10183788
TI - Executive forum: the planetree philosophy.
PMID- 10183789
TI - Executive forum: design for therapeutic outcomes.
AB - In summary, the two major characteristics of design for therapeutic outcomes are:
1) that it takes into account the functional requirements of patients as these
are influenced by illness or disability and 2) that it supports processes of care
and treatment aimed at specific desired outcomes. The challenge is a large one
and requires a multi-disciplinary effort. Nurses and physicians should be
included on design teams, whether in the planning of new facilities, or the
redesign of older ones. Physicians will be able to articulate the treatment
goals, as will experienced nurses who, in addition, have a handle on the day-to
day activities that can be more effectively carried out by or for patients with
the support of good design. In the endeavor to design for therapeutic outcomes,
nurses and physicians must be part of the design team, but we should not expect
all of them to have the same understanding of the built environment as a design
professional has. Rather, their input is an essential complement to the design
professional's skills and of critical importance in articulating the requisities
of specific patient groups. Because of cost considerations and because there are
many users within the hospital, there will of necessity be some trade-offs, but
concentration on what the therapeutic outcomes should be for different groups of
patients will go a long way toward achieving truly functional designs.
PMID- 10183790
TI - Long term care design: theory & types.
PMID- 10183791
TI - Long term care: future possibilities.
PMID- 10183792
TI - Long term care design: lighting.
PMID- 10183793
TI - Long term care: case studies.
PMID- 10183794
TI - Medical office design: theory & types.
PMID- 10183795
TI - Medical office design: Brigham West Medical Office Campus.
PMID- 10183796
TI - Medical office design: Brigham & Women's Hospital ambulatory services building
II.
PMID- 10183798
TI - Standards seen as a key to managing healthcare costs.
AB - Unless the HL7 standards group acts soon to develop timely, enforceable
standards, they may be overtaken by the public outcry to contain healthcare costs
immediately. Federal government representatives addressed a recent HL7 plenary
session and warned that the public finally understands that information is a
vital link in controlling runaway costs. They want standards now.
PMID- 10183797
TI - Medical office design: new possibilities.
AB - In summary, I have presented some unique projects that boldly deviate from our
expectations for healthcare facilities. Perhaps this will inspire design
professionals to look for opportunities to challenge "formula design" and to
envision new possibilities for the 21st century. Remember that design
professionals are creating the future today with every project they design.
PMID- 10183799
TI - Fledgling CPRI (Computer-Based Patient Record Institute) faces difficult
challenges as legislative clock ticks.
AB - A diverse group of users, vendors, employers, insurers and government officials
met in Washington in July for the Computer-Based Patient Record Institute's First
Annual Meeting. Deemed "the focal point" of legislation demanding automated
patient records, their task was to overcome a myriad of differences and form a
true coalition that can meet an ambitious, and some say unrealistic, deadline.
PMID- 10183800
TI - COBRA strikes again. Emerald Denise Johnson v. University of Chicago Hospitals.
PMID- 10183802
TI - Health policy at the crossroads.
PMID- 10183801
TI - Can a suicide machine trigger the murder statute? People v. Dr. Kevorkian.
PMID- 10183803
TI - Hospitals for health in the twenty-first century.
AB - The following article illustrates the crucial importance for the future of
hospitals of in-house education, and of the team approach to resolving problems,
through concerted efforts on the part of all the hospital personnel.
PMID- 10183804
TI - Baby friendly hospitals toward a baby friendly world.
PMID- 10183806
TI - Czechoslovak hospitals in crisis?
PMID- 10183807
TI - AIDS case raises questions about ERISA. Greenberg v. H&H Music.
PMID- 10183809
TI - Michigan court affirms parents' right to discontinue child's life-sustaining
support. In re: Joelle Rosebush, A Minor v. Oakland County Prosecutor.
PMID- 10183808
TI - Special report on taxation and health care delivery systems. The Geisinger case:
exempt status for HMOs within integrated delivery systems.
PMID- 10183805
TI - Designing the next generation of American hospitals.
AB - Change has always been a part of the hospital's operating environment, but the
changes predicted for American Hospitals during the next two decades pose
considerable challenge to those who manage health care services and those who
design medical facilities. The next generation of American Hospitals are
responding to changes in technology, availability of human resources and demand
of the public, private and government interest groups. Hospitals and architects
that understand the predictable changes and anticipate the unknown, will be able
to plan a facility that responds to the needs of future health care delivery.
PMID- 10183810
TI - Court allows suit against hospital for failure to retain X ray needed in
malpractice case. Rogers v. St. Mary's Hospital of Decatur.
PMID- 10183812
TI - The ADA and health facilities: some progress and problems.
PMID- 10183811
TI - Cap on medical malpractice damages not applicable to COBRA suit. Power v.
Arlington Hospital.
PMID- 10183813
TI - Rust corrodes: the First Amendment implications of Rust v. Sullivan.
PMID- 10183814
TI - High Court struggles to define "reasonable" payments to providers. Good Samaritan
v. Sullivan.
PMID- 10183815
TI - Medicare payment for graduate medical education in limbo. Methodist Hospitals of
Memphis v. Sullivan.
PMID- 10183816
TI - Comment: the constitutionality of fetal experimentation statutes: the case of
Lifchez v. Hartigan.
PMID- 10183818
TI - Recent R & D payoffs.
PMID- 10183819
TI - Westchester County Medical Center case sends powerful warning to hospitals.
PMID- 10183821
TI - Comment: United States Supreme Court upholds right to abortion subject to
increased state regulation. Planned Parenthood of Southeastern Pennsylvania v.
Casey.
PMID- 10183820
TI - Antitrust immunity granted in a far-reaching peer review case. Austin v.
McNamara.
PMID- 10183817
TI - Recent developments in HMO malpractice liability: Chase v. Independent Practice
Association.
AB - The court's decision in Chase demonstrates that an HMO or independent practice
association need not incur liability for the negligence of a physician if the
arrangement between the entity and the physicians who provide services on its
behalf is properly structured and maintained. IPA's successful defense of this
lawsuit was based upon: (1) careful structuring of an independent relationship
with the medical group, including appropriate wording in the contract
establishing the relationship; and (2) careful maintenance of the relationship
consistent with the terms of the contract to avoid giving patients any reason to
believe that an agency relationship existed.
PMID- 10183823
TI - While urging hospital unity, AHA tries to be conciliatory in healthcare reform
debate.
PMID- 10183822
TI - States get good news on Medicaid.
PMID- 10183825
TI - Non-acute AHA segment seeks support.
PMID- 10183824
TI - 'Renaissance' seen in drug development.
PMID- 10183826
TI - AIDS workshop. Sponsored by The HMO Group on February 27-28, 1992.
PMID- 10183831
TI - NAHAM focuses on healthcare reform & Medicaid outstationing.
PMID- 10183828
TI - Supreme Court reaffirms ERISA preemption. District of Columbia v. Greater
Washington Board of Trade.
PMID- 10183830
TI - Economic challenges of gram-positive infection. Symposium held in Florence,
Italy, Spring 1992.
PMID- 10183827
TI - U.S. health administration programs and Latin America: a need for direction.
Proceedings of an international workshop, January 4-5, 1990, Annapolis, MD.
PMID- 10183835
TI - Strategies for redesigning work of nursing in the OR.
PMID- 10183832
TI - Court rules physician denied fair hearing. Rosenblit v. Superior Court.
PMID- 10183834
TI - Curran encourages nurses to restructure environment.
PMID- 10183833
TI - Court rules patient has legal duty to reveal HIV status.
PMID- 10183829
TI - Hospital and doctors granted antitrust immunity in important peer review lawsuit.
Austin v. McNamara.
PMID- 10183837
TI - High Court hands down decision in Rogers v Whitaker.
AB - This is the first time that an issue related to the provision of medical
information or advice has been argued before the High Court of Australia. As with
any decision of the High Court, there will always be supporters and protagonists.
However, one of the benefits of having the High Court pronounce a judgement in
this area of law is that it provides the necessary guidance and consistency for
all the courts in Australia to follow whenever they are asked to address issues
relating to the provision of information or advice in medical negligence cases.
PMID- 10183836
TI - Straight talk.
PMID- 10183838
TI - Conference cites impact of foreign diseases on healthcare workers.
PMID- 10183839
TI - After miscarriage.
PMID- 10183840
TI - Myths of pain control in the dying addressed.
PMID- 10183843
TI - Purchasing intelligence--everybody's business. Proceedings of a conference held
at Gateshead 28 February 1992.
PMID- 10183846
TI - The AHA annual meeting: a trustee's report.
PMID- 10183841
TI - Healthcare reform: analyzing the issues.
PMID- 10183842
TI - AIDS and changes in clinical research methods.
PMID- 10183847
TI - The National Primary Care Conference.
PMID- 10183844
TI - Austin v. McNamara: antitrust immunity for peer review under the Health Care
Quality Improvement Act.
PMID- 10183845
TI - Mandatory testing of hospital employees exposed to the AIDS virus: need to know
or unwarranted invasion of privacy? Leckelt v. Board of Commissioners.
PMID- 10183848
TI - Geriatric care issues.
PMID- 10183854
TI - Pressure in Pa. mounts for tax settlements.
PMID- 10183850
TI - Tradition and transformation. Sponsors forge relationships to revitalize the
Catholic healthcare ministry.
AB - In September 1992 seven leaders of institutes of women religious met in St. Louis
to discuss the challenges facing sponsors of Catholic healthcare. One woman
religious from the Catholic Health Association also joined in the roundtable
conversation. The discussion ranged over a variety of topics but invariably
returned to one question: Given the current situation in healthcare, how can
sponsors use their leadership to foster relationships that ensure the continued
vitality of the Catholic healthcare ministry and promote a just and rational
healthcare system?
PMID- 10183849
TI - Discrimination against HIV-infected employee can result in termination of
hospital's Medicare and Medicaid funding. In the matter of Westchester County
Medical Center.
PMID- 10183851
TI - Patient challenges enforcement of agreement to pay hospital charges ... Doe v.
H.C.A., Health Services of Tennessee.
PMID- 10183853
TI - In the court of common sense. Community General Hospital v. Medical Staff of
Community General Hospital.
PMID- 10183856
TI - Administration hints at need for federal guidelines on hospitals' role under
reform.
PMID- 10183852
TI - Hospitals win battle with liability insurer ... St. Paul Fire & Marine Insurance
Company v. Edge Memorial Hospital.
PMID- 10183857
TI - The doctor as gatekeeper: ethical considerations.
PMID- 10183860
TI - Tax court overruled in Geisinger case.
PMID- 10183855
TI - Fetal tissue research.
PMID- 10183862
TI - Seventh Circuit limits scope of bloodborne pathogens regulations. American Dental
Association (ADA) v. Martin.
PMID- 10183859
TI - Towards a common vocabulary for identifying management issues in health projects.
AB - Management issues are one of the most important constraints in achieving social
sector development objectives. The practice of labeling a variety of operational
weaknesses as management problems hinders diagnostic power and, hence induces a
low probability of removing or reducing management constraints. Moreover terms
related to management are used differently. The set of terms presented here
disaggregates the concept of management into nine discrete measurable management
tasks: planning systems, beneficiary analysis, provision of goods and services,
procurement and logistics of materials, financing and budgeting, organizational
design, personnel, leadership, and control systems. The nine functional
management areas are applied to three stages of a project cycle, viz. sector
analysis/project identification, project design/project appraisal, and project
implementation/project supervision. The set of terms proposed is seen as a first
step towards developing a common vocabulary for identifying management issues in
health projects.
PMID- 10183863
TI - Strategies for improving nursing home care: a research roundtable.
AB - The findings reported here are from a group of researchers identified by the
authors for their leadership in the advancement of knowledge about nursing homes
as organizations. Three themes were identified from the current research
presented at the Roundtable. The first was a recognition of the pervasive which
society's conflicting expectations about nursing homes create for those who staff
them. The second related to the central, at times unsupervisable, role of non
professional staff. The third theme called attention to the reinforcement power
of supervision and leadership in bringing about positive change in care giving
staff. These issues and the research described had implications for both policy
and practice. While far from a comprehensive treatment of organizational and
managerial issues, the observations reported here represent new research interest
in nursing homes be considered simple organizations with stable and predictable
inputs. The processes of care and the way those processes are implemented vary
from one facility to another and, indeed, among nursing units within the same
facility. Broadbased practitioner-researcher collaborations are needed to promote
usable research on the internal processes of nursing homes. Future collaborations
will probably focus on how and why some procedures and structures produce better
results for residents and others. Policy makers and administrators will benefit
as the tools and methods of organizational research are used to identify the best
structures and practices in the nursing home industry. Similarly, the knowledge
base of long-term care administration will be enriched by contemporary
reconsideration of the structure and processes of nursing homes as organizations.
PMID- 10183861
TI - Watch out for: patient-prisoners with AIDS. Doe v. State of New York.
PMID- 10183864
TI - Report from the Third Annual Healthcare Safety and the Environment Symposium, Las
Vegas, February 1993.
PMID- 10183858
TI - The HMO Group conference: Utilization of Scarce Resources: (Utilization
Management II).
PMID- 10183865
TI - CEOs examine future challenges.
PMID- 10183867
TI - Minimally invasive surgery adds safety fears.
PMID- 10183866
TI - Discharge of nurse held actionable. Winkelman v. Beloit Memorial Hospital.
PMID- 10183870
TI - 1993 FAHS Annual Conference and Business Exposition. A scrapbook.
PMID- 10183868
TI - Health reform town meeting brings leaders together.
PMID- 10183873
TI - NMHCC (National Managed Health Care Congress) speakers call for more data,
patient empowerment.
PMID- 10183871
TI - Rural hospital leaders gather for annual symposium.
PMID- 10183874
TI - Healthcare industry embraces imaging technologies at AIIM (Association for
Information and Image Management).
AB - Healthcare and high-tech writer Rob Hard scoured the exhibit hall at the huge
Association for Information and Image Management (AIIM) annual conference. He
discovered that healthcare professionals are seeking ways to redesign workflow
and incorporate the technology into their business plans.
PMID- 10183872
TI - If we knew then what we know now: planning for people with AIDS.
PMID- 10183869
TI - Antitrust concerns in managed care provider negotiations. United States v. A.
Lanoy Alston, DMD, P.C., et al.
AB - Contract negotiations between managed care organizations and providers are
potential legal traps, loaded with antitrust implications. A recent court action
involving dentists is instructive on the issues for all providers.
PMID- 10183875
TI - Hospital's duty to protect patients explored. Young v. Huntsville Hospital.
PMID- 10183876
TI - Court grants HCQIA immunity in antitrust suit by physician. Smith v. Ricks.
PMID- 10183877
TI - ALJ finds neglect by Medicare Part B carrier. B.G. v. Travelers Insurance Co.
PMID- 10183880
TI - Reform gets boost from trustees.
PMID- 10183878
TI - Plastic surgery.
AB - Plastic surgery is all too often thought of as an indulgence of the rich and
famous with little attention paid to the repair of bodies and limbs disfigured or
deformed by accident or illness. Surgeons look to management to address those
issues that create an insecure base for planning the service and for its
organisation nationwide.
PMID- 10183879
TI - Endoscopic safety: protecting OR personnel.
PMID- 10183881
TI - Perspectives. Inner cities view reform with hope and doubt.
PMID- 10183882
TI - Anatomy of an ADA case. Chatoff v. City of New York.
AB - This article addresses plaintiff and defense strategies in the context of an ADA
case and is intended to serve as a ready reference to employer's counsel when
faced with ADA litigation. In an ADA case, it is essential that counsel humanize
the employer by keeping the "Our Business Supports Diversity" theme before the
trier of facts at all times. This theme should be accompanied by the proposition
that plaintiff's demands are not reasonable because they impose an undue burden
on the employer or a risk to the safety of the employee or others in the
workplace. It is also crucial for defense counsel to become familiar with the
plaintiff's attorney's strategic considerations. ADA litigation strategy is
illustrated by reference to Chatoff v. City of New York, a landmark ADA case
instituted on behalf of the approximately 200,000 hearing-impaired residents of
the City of New York, demanding equal and direct access to Emergency 911
services.
PMID- 10183885
TI - Court rules medical staff bylaws are not a contract. Robles v. Humana Hospital
Cartersville.
PMID- 10183883
TI - Recent decision leaves gap in peer review discovery protections. Pagano v.
Oroville Hospital.
PMID- 10183884
TI - Challenges facing hospital partnerships.
PMID- 10183888
TI - Biomedicine and bioethics: de lege lata, de lege ferenda. "... the law today, as
laid down, and what tomorrow may bring.".
PMID- 10183886
TI - Bartley v. Eastern Maine Medical Center: cost containment prevails over
physicians' rights!
PMID- 10183889
TI - Falcon v. Memorial Hospital: a rational approach to loss-of-chance tort actions.
PMID- 10183891
TI - Engelhardt cites two challenges for health care reform policy.
PMID- 10183895
TI - Corcoran v. United Healthcare, Inc.: liability of utilization review companies in
light of ERISA.
PMID- 10183894
TI - First Healthier Communities Summit, San Francisco, April 1993.
PMID- 10183898
TI - New healthcare era to require reformed style of management.
PMID- 10183890
TI - Donaldson v. Van de Kamp: cryonics, assisted suicide, and the challenges of
medical science.
AB - In recent years, advances in medical science have left the legal community with a
wide array of social, ethical, and legal problems previously unimaginable.
Historically, legislative and judicial responses to these advances lagged behind
the rapid pace of such developments. The gap between the scientist's question,
"Can we do it?," and the lawyer's question, "Should/may we do it?'" is most
evident in the field of cryonics, with its technique of cryonic, or cryogenic,
suspension. In cryonic suspension, a legally dead but biologically viable person
is preserved at an extremely low temperature until advances in medical science
make it possible to revive the person and implement an effective cure. The
terminally ill patient who wishes to benefit from such treatment is faced with
the dilemma that present life must be ceased with hope of future recovery. As a
result, the process challenges our traditional notions of death and the prospects
of immortality while raising a host of concomitant legal dilemmas. Some facets of
this dilemma are exemplified by Donaldson v. Van de Kamp. In Donaldson, Thomas A.
Donaldson sought the declaration of a constitutional right to premortem cryonic
suspension of his body and the assistance of others in achieving that state.
Donaldson, a forty-six-year-old mathematician and computer software scientist,
suffers from a malignant brain tumor that was diagnosed by his physicians in
1988. This tumor is inoperable and continues to grow and invade his brain tissue.
Donaldson's condition will gradually deteriorate into a persistent vegetative
state and will ultimately result in death. Physicians predict his probable death
by August 1993. Donaldson petitioned the California courts, seeking a declaration
that he had a constitutional right to achieve cryonic suspension before his
natural death. His doctors believe that if Donaldson waits until his natural
death to be suspended, future reanimation will be futile because the tumor will
have destroyed his brain. In addition, Donaldson's doctors sought an injunction
against criminal prosecution for their participation in the suspension, because
Donaldson, once suspended, would be considered "dead" under California law.
Donaldson and his doctors built their novel argument upon the recent right-to-die
cases in which the courts recognized a patient's right to have life-sustaining
medical treatment withdrawn. Donaldson argued that his right to privacy and self
determination is paramount to any state interest in maintaining life. Thus,
according to Donaldson, balancing the state's reasons to end--or "interrupt," as
cryonics enthusiasts would have it--his own life was not necessary. The trial
court dismissed the complaint for failure to state a cause of action, and
Donaldson appealed to the California Court of Appeals. Because the cryonic
process would necessarily involve physician-assisted death, or the aiding,
advising, or encouraging of another to commit suicide, the appellate court
affirmed the ruling of the trial court, holding that Donaldson did not have a
constitutional right to assisted death. Additionally, in light of Donaldson's
First Amendment challenge to the statute, the court upheld the criminal statute
prohibiting the aiding, advising, or encouraging of another to commit suicide.
This Note briefly discusses the process of cryonic suspension and explores the
holding of Donaldson in light of the underlying rationale of the California right
to-die cases. Considering the contradictory state and individual interests
balanced in the right-to-die cases, this Note concludes that, under a similar
balancing test, premortem cryonic suspension could be permitted under certain
circumstances; however, the right to premortem cryonic suspension may be more
effectively recognized through legislation.
PMID- 10183892
TI - Carla Myers case decided in Ohio.
PMID- 10183896
TI - Awareness of gangs can help hospitals head off conflict.
PMID- 10183897
TI - Execs urged to forego rhetoric, embrace healthcare reforms.
PMID- 10183899
TI - Physician support needed to create integrated system.
PMID- 10183901
TI - Communication efforts help rural facility recover, flourish.
PMID- 10183900
TI - Reform to pose challenges for nation's hospital trustees.
PMID- 10183887
TI - Assessing doctors as reasonable doctors and as reasonable persons: a reminder in
the context of negligent transmission of HIV during artificial insemination. Ter
Neuzen v. Korn.
PMID- 10183893
TI - Limitation of autonomy is focus of IBI conference.
PMID- 10183902
TI - Rural hospitals need to lead in forging health partnerships.
PMID- 10183903
TI - Execs discuss challenges of community-focused networks.
PMID- 10183904
TI - "Dangerous to himself and/or others" ... Menendez v. Superior Court of Los
Angeles County.
PMID- 10183906
TI - Blazing the health reform trail: new directions, new challenges. ASIM's 1993
Leadership Development Conference.
PMID- 10183905
TI - Aspects of a computer-based patient record.
PMID- 10183907
TI - Reform is coming with or without Washington.
PMID- 10183908
TI - Courts deny relief to physicians in suits against hospitals. Katz v. Children's
Hospital Corporation; Bartley v. Eastern Maine Medical Center.
PMID- 10183909
TI - Medicare benefits decisions favor beneficiaries. Hill v. Sullivan; Deluca v.
Sullivan.
PMID- 10183911
TI - Strategies for successful information system development.
PMID- 10183910
TI - The payment issue in the termination of care context. Grace Plaza of Great Neck
v. Elbaum.
PMID- 10183913
TI - A glossary of terms. Managed care.
PMID- 10183912
TI - On the path to healthcare reform. The 78th Annual Catholic Health Assembly.
AB - A healthcare revolution is at hand, and not just in Washington, DC. The 78th
Annual Catholic Health Assembly, held June 6 to 9 in New Orleans, drew 1,300
Catholic health providers from across the nation to explore the progress of
healthcare reform--at the federal level, in state initiatives, and in cities
across the nation where providers are collaborating to provide more
comprehensive, cost-effective care. Culminating in an affirming address by First
Lady Hillary Rodham Clinton, the assembly afforded attendees opportunities to
discuss the operational opportunities ahead, innovative care approaches, and
strategies to maintain their Catholic identity and values under a reformed
system.
PMID- 10183914
TI - The continuing quest for excellence in health care delivery.
AB - At the recent Perspectives in Medical Management conference in New Orleans, more
than a dozen sessions focused on issues of medical quality management. Speakers
discussed total quality management, explaining its features and how physician
executives can implement strategies in their organizations. Others talked abut
the benefits and applications of clinical benchmarking and clinical guidelines,
while still others described how their organizations custom-tailored quality
programs to meet their needs. Some of the highlights of the meeting are
summarized on the following pages.
PMID- 10183915
TI - RBRVS physician payment: moving beyond Medicare.
PMID- 10183916
TI - Managed care competition and the antitrust laws. U.S. Healthcare, Inc. v.
Healthsource, Inc.
PMID- 10183917
TI - No tax exemption for Geisinger Health Plan. Geisinger Health Plan v.
Commissioner.
PMID- 10183918
TI - Enforceability of managed care contract provisions limiting provider-patient
contacts after contract termination. Humana Medical Plan, Inc. v. Jacobson.
PMID- 10183919
TI - Healthcare reform terminology.
PMID- 10183920
TI - Recommendation for a single procedure classification system. National Committee
on Vital and Health Statistics Subcommittee on Medical Classification Systems.
PMID- 10183921
TI - Loss of medical records--a separate tort. Rodgers v. St. Mary's Hospital of
Decatur.
PMID- 10183922
TI - National provider groups converge on New Jersey Boren suit. Appeal hinges on
highest practicable level of care.
PMID- 10183923
TI - Tax-exempt hospitals: Dingell retries State of Texas v. The Methodist Hospital.
PMID- 10183924
TI - ERISA permits employer cancellation of promised retiree health benefits,
according to Fifth Circuit. Wise v. El Paso Natural Gas Co.
PMID- 10183925
TI - Managing change.
AB - Managing Change was the title of this year's IHSM Annual Conference, held in
Birmingham on 9/11 June. One of the most important events in the year for health
services managers, a record 1300 people attended to discuss the change in health
services in the UK and beyond.
PMID- 10183926
TI - Laboratorians advised to practice 'safe science'. Lab-related findings from the
IX International Conference on AIDS.
PMID- 10183928
TI - Texas Supreme Court rules Mary Carter agreements void as contrary to public
policy. Elbaor v. Smith.
PMID- 10183927
TI - Revoking hospital privileges: new directions in Ontario. Dr. N. v. Brantford
General Hospital.
AB - Recent decisions by the Ontario Hospital Appeal Board have helped hospital boards
understand the importance of due process when revoking a physician's hospital
privileges. The authors illustrate the need to have a mechanism to suspend
privileges immediately but which also provides physicians with the opportunity to
respond to allegations. The article outlines 11 clauses that serve as a practical
guide to due process and can be added to hospital by-laws.
PMID- 10183929
TI - Health insurer's denial of coverage upheld by fifth circuit. Irion v. Prudential
Insurance Company of America.
PMID- 10183930
TI - Practical considerations relating to apparent possible physician impairment.
Kozlowski v. Rush.
PMID- 10183931
TI - McGann offspring: employers may retroactively limit health insurance, says 11th
Circuit. Owens v. Storehouse, Inc.
PMID- 10183932
TI - "Town meeting" offers general surgeons an open forum. Assembly For General
Surgeons, April 1993, Montreal.
PMID- 10183933
TI - Experts discuss ways to gear up for OR safety.
PMID- 10183934
TI - Aspen update on Sacramento-Sierra Medical Group.
PMID- 10183935
TI - Down by law.
AB - Will legal challenges to health authorities be more successful than before the
reforms? Jean McHale and David Hughes report on the case of Rhys Daniels.
PMID- 10183936
TI - United States v. Levin: entrapment by estoppel doctrine applied in Medicare
reimbursement context.
AB - The decision in Levin reaffirms that health care providers should be entitled to
rely in good faith on official interpretations and representations by authorized
government officials as to the propriety of their conduct under the Medicare
program. Although the doctrine of entrapment by estoppel was developed as a due
process defense to a criminal prosecution, the fundamental notions of fairness
underlying the doctrine should be applicable as well as in a civil action. Thus,
the defense of entrapment by estoppel should be available, for example, in the
context of civil health care reimbursement recoupment audits, where a provider
has acted in reliance on the interpretation of a statute or regulation by the
appropriate administrative agency charged with its enforcement.
PMID- 10183937
TI - Is osseointegration a requirement for success in implant dentistry?
AB - The term 'osseointegration' was coined in 1977. This term gained popularity and
has been extensively used, but with various and diverging meanings; therefore,
there is a strong need to redefine it. We propose a definition of the concept of
osseointegration grounded on a physical basis. Since bioactive biomaterials are
more strongly integrated than inert ones (e.g. titanium or alumina), and since
osseointegration is a word implying strong bonding, we propose to devote the use
of the concept of osseointegration for materials which are most successfully
integrated into bone, i.e. when the bone/implant interface is a diffuse interface
with full chemical bonding, such as for bioactive biomaterials. If the
bone/implant interface is a sharp one, the concept of osseointegration is no
longer relevant and we propose use of the term 'osteal integration', i.e. for
inert biomaterials, such as titanium and alumina. Based on this proposition, we
assert that osseointegration is not a requirement for success in implant
dentistry.
PMID- 10183938
TI - Non-technical factors could limit MRA use.
PMID- 10183939
TI - Interventionalists find new uses for old tools.
PMID- 10183940
TI - Transfer of 99mTc-DTPA, lung surfactant and lung injury: a review of the
literature.
AB - Measurement of the alveolo-capillary transfer of radiolabelled solutes provides
information about the integrity of the alveolo-capillary barrier. The transfer
of 99mTc-diethylen triamine penta-acetate ( 99mTc-DTPA) can be easily measured
after tracer delivery in aerosol form and external monitoring of radiation over
the lung. Although the technique has been used extensively for more than ten
years, the basic mechanisms for pulmonary clearance of 99mTc-DTPA remain
incompletely understood. Experimental evidence that the rate of clearance partly
reflects the functional integrity of the pulmonary surfactant system is reviewed
together with clinical studies with possible relation to surfactant function.
PMID- 10183941
TI - CO 2 laser surgery in hemophilia treatment.
AB - The use of CO 2 laser surgery between 1985 and 1991 in South Africa and Portugal
for treatment of disorders in patients with mild to moderate cases of hemophilia
A is discussed. Six cases of oral procedures and excision of skin tumors
performed during this period are reported. In most of the cases of mild
hemophilia no pre- or postoperative infusion of Factor VIII or desmopressin
(DDAVP) was required. In some cases of moderate hemophilia, patients were
infused with desmopressin (0.3 mug/kg body weight) and were treated
postoperatively with the use of nasal desmopressin spray (150 mug to each nostril
for four weeks following surgery). Factor VIII levels were measured before
surgery. Follow up of four weeks was uneventful. The mean average power of the
CO 2 laser was 20 W continuous and the pulse duration was 0.1 s for ablational
procedures. For dermatologic procedures, a flexible plastic CO 2 laser hollow
fiber was used (Flexilase, Sharplan, Allandale, NJ). We concluded that CO 2
laser surgery for hemophiliacs has a confirmed place in modern laser technology
provided the standard precautions are taken and facilities are available.
PMID- 10183942
TI - Endoscopy fits definition of medical imaging.
PMID- 10183943
TI - ACR system enhances mammography reporting.
PMID- 10183944
TI - Sensors for implantable pacemakers.
AB - Cardiac pacemaker technology has progressed greatly since the first implantable
pacemaker was invented in the 1950s. The most recent improvement incorporates
sensors that measure the body's metabolic responses and then appropriately pace
according to these measurements. This article reviews this technology and
examines the various sensors used in rate-responsive pacemakers.
PMID- 10183945
TI - Optical fiber biochemical sensors for continuous monitoring.
AB - As the market for biosensors continues to grow, scientists are striving to fill
the need for sensors for monitoring specific biochemicals. Receptor-based optical
sensors show some promising advantages over other sensor types, particularly for
use in vivo. Until now, these sensors have been too costly to produce for the
commercial market. This article describes the various sensors that have been
developed and detection methods that use optical fibers, as well as a proposed
new configuration for a reversible optical biosensor.
PMID- 10183946
TI - Treatment of congenital and acquired hemophilia patients by extracorporeal
removal of antibodies to coagulation factors: a review of US clinical studies
1987-1990. Hemophilia Study Group.
AB - This paper reviews the use of extracorporeal immunoadsorption with immobilized
Staphylococcal Protein A in attempts to lower the inhibitor titer in 22 patients
with either congenital hemophilia or with acquired inhibitors. Eighty-five
immunoadsorption procedures were performed at 13 locations in the United States
between June, 1987 and February, 1990. In general, immunoadsorption was shown to
efficiently remove IgG and, in eight congenital hemophilia patients, it also
produced a clinically significant lowering of inhibitors allowing effective
conventional factor replacement therapy. Three of thirteen congenital hemophilia
patients treated received factor concentrate prior to immunoadsorption and were
anamnestic at the time of treatment. Although they experienced substantial
lowering of their inhibitor titers, it was not sufficient to allow effective
factor replacement. The effectiveness of immunoadsorption therapy in the 9
patients with acquired inhibitors was more difficult to evaluate due to the wide
variety of concomitant medications which were employed, although in several
patients serious bleeding episodes were substantially improved (or halted)
following immunoadsorption. Side effects associated with immunoadsorption were
slight. These findings suggest that immunoadsorption can be a significant
benefit to patients with inhibitors, particularly if it is instituted prior to
factor administration.
PMID- 10183947
TI - The spine and spinal cord.
PMID- 10183948
TI - Functional studies of the human brain using high-speed magnetic resonance
imaging.
AB - Dramatic technical advances in magnetic resonance imaging (MRI or NMR) scanning
speed and recent governmental approval for the routine use of NMR contrast agents
have yielded techniques for quantitative imaging of cerebral hemodynamics. The
technical basis of ultrafast imaging, the methodology of dynamic imaging with
contrast agents, and results in normal subjects and patients are presented.
PMID- 10183950
TI - Kidneys: combining morphology and function.
PMID- 10183949
TI - Musculoskeletal: growing role in lesion evaluation.
PMID- 10183951
TI - Practice guidelines. Efficacy and implementation in HMOs.
PMID- 10183952
TI - Geriatric care in HMOs.
PMID- 10183953
TI - HIV positive surgeons must tell their patients. Kerins v. Hartley.
PMID- 10183954
TI - Joint Commission indicator monitoring system: from beta test to nation-wide
implementation.
PMID- 10183955
TI - Computer networks.
AB - We have looked at several aspects of networks in this article. As you read about
networks, and use them, we hope our discussions will help you understand some of
the associated concepts and terms. For instance, suppose someone describes an
Ethernet installation as a bus topology LAN using the 1-persistent CSMA/CD
protocol with horizontal cables on each floor connected by repeaters to a
vertical cable backbone running from the basement to the roof. You now have seen
what that description implies. To close this article, we ask you to refer back to
Figure 1. Our sample network transfer from Marie to Lars was described as being
accomplished through a number of layers or steps, most of which were transparent
to the users. Building upon the material presented in this article, we can now
give you a more detailed illustration of those layers. Figure 13 shows the seven
layers in network model defined by the International Standards Organization, ISO:
application, presentation, session, transport, network, data link, and physical.
We do not have space here to discuss each layer in detail, but Figure 13 does
give a typical operation that is done in each layer.
PMID- 10183956
TI - Privacy on trial in Massachusetts: Commonwealth v. Stockhammer.
AB - Health records are not always private. In this case, the court said that a
defendant in a rape case could see certain medical records pertaining to the
victim's hospitalization for an unrelated overdose that occurred months after the
attack. This article explores the legal decision and its impact on medical
privacy.
PMID- 10183957
TI - AHIMA's second annual Confidentiality Symposium.
PMID- 10183958
TI - First lady lauds hospitals; promises antitrust relief.
PMID- 10183960
TI - The jargon of health system reform.
PMID- 10183959
TI - Transplantation and organ procurement: past experiences, emerging challenges.
PMID- 10183962
TI - 1993 International Hospital Symposium for Efficient Energy Use.
PMID- 10183961
TI - ERISA does not preempt state insurance law regulating preferred provider
organizations. Stuart Circle Hospital Corp. v. Aetna Health Management.
PMID- 10183963
TI - 1993 International Hospital Symposium for Efficient Energy Use. July 1-3 in
Berlin, Germany.
AB - Health Facilities Management editor Michael Hemmes attended the International
Hospital Symposium for Efficient Energy Use (ISHE '93) at the invitation of
Landis & Gyr Powers AG, which sponsored the event. Hemmes was part of an eight
member U.S. delegation. Here is his report.
PMID- 10183964
TI - The quiet revolution.
AB - The IHSM's day conference threw a wide spotlight on 'alternative settings for
acute care'. The occasion provided a powerful and unifying commentary on a number
of trends discernible in most of the specialties examined in the Medicine for
Managers series.
PMID- 10183966
TI - State hospital associations participate in 'dialog' on IMS (indicator monitoring
systems).
PMID- 10183965
TI - What price patient restraint? Orwick v. Fox.
PMID- 10183967
TI - Venice Hospital decision vacated. Key Enterprises of Delaware, Inc. v. Venice
Hospital.
AB - The United States Court of Appeals for the Eleventh Circuit recently ordered an
en banc rehearing of its widely reported hospital downstream diversification
antitrust case. The so-called Venice Hospital case had found antitrust liability
in the operation of a durable medical equipment (DME) joint venture between a
hospital and a DME vendor. The Eleventh Circuit, however, has vacated its prior
decision and, pending its en banc opinion, reinstated the district court's
decision that the defendants did not violate antitrust law.
PMID- 10183968
TI - DRGs: labels, information and uncertainty.
AB - This paper presents a new perspective on why Diagnosis Related Groups (DRGs) are
successful. It begins with a characterisation of labels we use to describe their
attributes and a brief overview of the Commonwealth Australian National Diagnosis
Related Group (AN-DRG) localisation project. Information required and produced by
AN-DRGs computer programs is then outlined to establish their domain of
application. Uncertainty in such information limits the utility of DRGs as a
planning and managing tool. Examples are presented to clarify their statistical
properties and to motivate discussion regarding technology for improving their
performance.
PMID- 10183969
TI - Report from the NIOSH workshop on engineering controls for preventing airborne
infections.
PMID- 10183970
TI - Hospitals and physicians may--or may not--be liable for defective medical
products. Garcia v. Edgewater Hospital.
PMID- 10183971
TI - Hospital had no duty to admit child to its PICU when unit was full and on a fly
by status. Davis v. Johns Hopkins Hospital.
PMID- 10183972
TI - Rationing: another contradiction in the health care debate.
PMID- 10183974
TI - Whose patients are they, anyway? Humana Medical Plan, Inc. v. Jacobson.
PMID- 10183973
TI - DuPont/HFM Forum on carpet in health care facilities. Roundtable discussion.
AB - DuPont and Health Facilities Management magazine invited 20 national experts to
Dalton, GA--the carpet-manufacturing capital of the world--on May 13 to take part
in DuPont's first-ever Forum on Carpet in Health Care Facilities. During the two
hour roundtable discussion, moderated by DuPont's C. Jack Murph and HFM's Michael
Hemmes, end-users, interior designers and mill representatives talked about the
aesthetic, economic and performance aspects of using carpet in health care
settings. Here's an edited version of what they said.
PMID- 10183975
TI - Court authorizes disclosure of physician's treatment records. State Board of
Medical Examiners v. Fenwick Hall, Inc.
PMID- 10183976
TI - Court finds basis for hospital liability on informed consent theory. Friter v.
Iolab Corp.
PMID- 10183977
TI - Divided court reverses judgment NOV (notwithstanding the verdict) for physician.
Dent v. Perkins.
PMID- 10183978
TI - The role of the National Institutes of Hospital Management in national health
care system development: report of an international seminar.
PMID- 10183979
TI - Survey findings and conclusions of a workshop on health care demand in El
Salvador.
PMID- 10183980
TI - Field operations and written policy. What you don't know can hurt you. Greater
Houston Transport v. Zrubeck.
PMID- 10183981
TI - Employer unwittingly creates ERISA plan. Randol v. Mid-West Nat'l Life Ins. Co.
PMID- 10183982
TI - CHA task force assesses strengths, needed changes in Clinton draft plan.
PMID- 10183984
TI - 'Clinics without walls' seeking stronger ties with large systems.
PMID- 10183983
TI - Seminar for journalists, congressional staff urges consensus on reform.
PMID- 10183985
TI - Finance gimmicks offered to aid sales.
PMID- 10183986
TI - The changing role of volunteerism.
AB - As the number of Americans who volunteer grows, the definition of "volunteer" is
becoming more broad. In addition to the traditional volunteer opportunity, there
are community service, student internship, and court-ordered service programs,
all of which pose a set of complicated managerial questions for those charged
with designing and running volunteer programs. Today, volunteers' motives may
extend further than the simple desire to help their neighbor. For example, given
the tough job market, some individuals are volunteering as a possible bridge to
employment, and are eager to learn skills and gain experience that they might
transfer to a new work setting. The growth in the number of volunteers is not
without its down side, however. As governments have cut back on service programs,
some responsibilities traditionally assumed by government are being shunted to
volunteer organizations, an inappropriate solution. Although volunteer programs
deserve support, governments cannot be let off the hook. Volunteers cannot and
should not replace paid staff. There are a number of exciting and innovative
approaches to recruiting, managing, and motivating volunteers. Some programs are
responding to the new kinds of volunteers by restructuring the volunteer
opportunity to make it more accessible to those who work from 9 to 5. Others are
responding to the diversity of the communities they serve by seeking training in
cultural sensitivity and recruiting volunteers from the community. Whatever the
volunteer opportunity, the screening and placement interview is a crucial first
step. It should be used to clarify expectations--of the volunteer and of the
volunteer administrator. Once volunteers are on board, the key to managing and
retaining volunteers is to recognize what motivates the individual volunteer-
whether it is the desire to acquire job-related skills, to socialize, or simply
to learn new things--and to provide the volunteer with these opportunities.
Continuing education, training, and feedback are essential ingredients of any
volunteer program. Another key to retaining volunteers is appropriate
recognition. Although volunteers may appreciate the traditional pin or letter of
thanks, volunteer administrators should explore other means of recognition that
are tied in to the individual volunteer's motives for volunteering in the first
place. Involving volunteers in the development and refinement of the volunteer
program and considering their suggestions for improvements are important ways of
keeping them involved and signaling recognition of their expertise and
value.(ABSTRACT TRUNCATED AT 400 WORDS)
PMID- 10183987
TI - Principal diagnosis and episodes of care: turning the corner in patient
information.
PMID- 10183988
TI - Report on the joint AUPHA/CDC workshop on promoting linkages between epidemiology
and health administration.
PMID- 10183989
TI - An overview of the heart and cardiac care. A glossary of cardiac anatomy, major
diseases, diagnostic procedures, and treatment interventions.
PMID- 10183991
TI - Changes in P & T Committee function, role of pharmacists under managed care, and
more.
PMID- 10183990
TI - Clarifying quality management terminology.
PMID- 10183993
TI - Dentists and physicians wiggling out of National Practitioners' Data Bank?
American Dental Association v. Shalala.
PMID- 10183992
TI - Thunder from California: the Thor decision and the ever-expanding right to die.
PMID- 10183994
TI - DuPont/HFM Forum on Carpet in Health Care Facilities. Second in a series.
Roundtable discussion.
AB - DuPont and Health Facilities Management magazine invited 20 national expert to
Dalton, GA--the carpet-manufacturing capital of the world--on May 13 to take part
in DuPont's first-ever Forum on Carpet in Health Care Facilities. During the two
hour roundtable discussion, moderated by DuPont's Jack Murph and HFM's Michael
Hemmes, end-users, interior designers and carpet mill representatives talked
about the aesthetic, economic and performance aspects of using carpet in health
care settings. Here's an edited version of what they said.
PMID- 10183995
TI - Emergency blood transfusion for Jehovah's Witness patient upheld. In the Matter
of Alice Hughes.
PMID- 10183996
TI - Survey shows optimism for CPR (computerized patient record).
PMID- 10183997
TI - Association of Healthcare Philanthropy International Conference. With health-care
reforms, hospitals need philanthropy more.
PMID- 10183998
TI - Improving organizational performance: a new name for an old process.
PMID- 10183999
TI - Matching physician supply with health care needs: current status, future
directions.
PMID- 10184000
TI - Health reform: rumors, rumblings and reality.
PMID- 10184002
TI - Standing tough on internists' issues. President's Address.
PMID- 10184001
TI - Quality care in a reformed system--views from Elders, Eisenberg.
PMID- 10184004
TI - Reform will usher in major role changes for GPOs.
PMID- 10184003
TI - Overcoming obstacles with strong-willed optimism. Inaugural Address.
PMID- 10184005
TI - Use and misuse of pharmacoeconomic terms: a definitions primer.
AB - Given the current cost-conscious health care environment, pharmacists must now be
able to assess the effects of an agent from safety, efficacy, and value
considerations. This article describes the various methodologies that may be used
in performing pharmacoeconomic analyses and highlights the use and misuse of
pharmacoeconomic terminology. Case studies relating the use of these methods to
the pharmacy practice setting are presented. The technical nuances of the various
methods are explained to promote a better understanding of the appropriate use of
these techniques and the terminology used to describe them.
PMID- 10184007
TI - Provider contracting workshop.
PMID- 10184006
TI - The DeGrella case. Implications and opportunities.
PMID- 10184008
TI - ADA's focus: carving a niche in healthcare reform.
AB - Healthcare reform was the pressing topic at the 76th Annual American Dietetic
Association (ADA) meeting and exhibition held in Anaheim, California, in late
October. Explained ADA President Susan Calvert Finn, Ph.D., R.D., about the
program content, "This meeting, by addressing new evidence of the link between
diet and disease, as well as the role of nutrition services as a preventive
health strategy, is extremely relevant to today's healthcare reform discussions.
The connection between diet and disease will be highlighted so policy makers
working on the healthcare reform bill will understand the medical importance of
our research."
PMID- 10184009
TI - California Supreme Court decision clarifies and confirms right to die decisions.
Thor v. Superior Court.
PMID- 10184010
TI - Symposium on Quality Assurance and Medical Audit in Hospitals, held July 25,
1992, New Delhi.
PMID- 10184011
TI - Scenes from Maui. Special Edition Symposium on Integrated Healthcare.
PMID- 10184012
TI - Health care execs must re-engineer themselves to keep pace with industry.
PMID- 10184013
TI - Leadership and community collaboration.
PMID- 10184014
TI - DuPont/HFM Forum on carpet in health care facilities. Third in a series.
AB - DuPont and Health Facilities Management magazine invited 20 national experts to
Dalton, GA--the carpet-manufacturing capital of the world--last year to take part
in DuPont's first-ever Forum on Carpet in Health Care Facilities. During the two
hour roundtable discussion, moderated by DuPont's C. Jack Murph and HFM's Michael
Hemmes, end-users, interior designers and carpet mill representative talked about
the aesthetic, economic and performance aspects of using carpet in health care
settings. Here's an edited version of what they said.
PMID- 10184015
TI - Hospitals strive to cut nosocomial infection rates.
PMID- 10184016
TI - Catholic identity is based on flexible, reasonable tradition.
PMID- 10184017
TI - Long-term care providers position themselves for the future.
PMID- 10184018
TI - Guidelines for minimal data security measures for the protection of computer
based patient records.
PMID- 10184019
TI - Glossary of managed care terms.
PMID- 10184020
TI - Restrictions on use of the title "Doctor": College of Physicians and Surgeons v.
Cheung.
PMID- 10184021
TI - Giving birth to the future.
PMID- 10184022
TI - Take another look at the medical staff bylaws. Mann v. Johnson Memorial Hospital.
PMID- 10184023
TI - Nurse's termination for refusal to treat AIDS patient upheld by federal court.
Armstrong v. Flowers Hospital, Inc.
PMID- 10184024
TI - Third-party claim asserted in EMTALA (Emergency Medical Treatment and Active
Labor Act) litigation. McDougal v. LaFourche Hospital Service District.
PMID- 10184026
TI - Civil rights not charity for people with disabilities.
PMID- 10184025
TI - 'Nothing about us without us!'.
PMID- 10184027
TI - 1994 Presidents' Forum.
AB - Maximizing limited financial resources, organizing multi-disciplinary
partnerships among members and allied associations, and strengthening strategic
planning initiatives were the key topics of concern to the presidents of ACFSA,
ADA, ASFSA, ASHFSA, DMA, HFM, NACUFS and SFM when they convened in Little Rock,
AR, for this year's prestigious Forum.
PMID- 10184028
TI - Court voids physician medical office building leases on fraud and abuse grounds.
Vana v. Vista Hospital Systems, Inc.
PMID- 10184029
TI - Florida Supreme Court provides way out for hospitals in treatment refusal
situations. In re Dubreuil.
PMID- 10184030
TI - Appellate court upholds denial of motions for summary judgment in malpractice
case. Walker v. Bell.
PMID- 10184031
TI - Hospital's assignment of its rights against physician to patient upheld. Deal v.
Kearney.
PMID- 10184033
TI - Outpatient versus inpatient surgery poses legal issues. Downey v. Mitchell.
PMID- 10184032
TI - Appeals court upholds dismissal of HIV-positive technician. Bradley v. U. of
Texas M.D. Anderson Cancer Center.
PMID- 10184034
TI - Elements of a national health information infrastructure.
PMID- 10184035
TI - Physician's abuse of female hospital employees may be 'hostile environment'
sexual harassment. Kopp v. Samaritan Health System, Inc.
PMID- 10184036
TI - Could a clinical mistake land you in jail?
AB - Internist Gerald Einaugler is facing 52 consecutive weekends in New York's
notorious Riker's Island jail because he was slow to hospitalize a terminally ill
nursing-home patient. A jury convicted the Brooklyn physician last June of
reckless endangerment and willful neglect, both misdemeanors. He has lost his
privileges at a hospital and two nursing homes, and has been disqualified as a
Medicaid provider. He may also lose is medical license. What he considered
conservative management, a prosecutor saw as criminal neglect, a deliberate
attempt to thwart appropriate treatment.
PMID- 10184037
TI - The Clinton Administration's healthcare reform plan.
PMID- 10184038
TI - Save me the wishbone, Ma.
PMID- 10184040
TI - Callahan hosts reform forum in Mobile.
PMID- 10184039
TI - RSNA (Radiological Society of North America) recap. Highlights of a show that
never ends.
PMID- 10184041
TI - Healthcare reform: surviving the shift from the hospital business to the
healthcare business.
PMID- 10184043
TI - Health maintenance organizations may refuse to deal with physicians. Capital
Imaging Associates v. Mohawk Valley Medical Associates.
PMID- 10184042
TI - Satisfaction with hospital care and interventions after pregnancy loss.
AB - Hospital practices after pregnancy loss have changed considerably over the past
decade, yet they have not been well evaluated. In a longitudinal study of 194
women and men who experienced miscarriage, ectopic pregnancy, stillbirth, or
newborn death, the recommended interventions at the time of loss are examined. In
most cases, parents were more satisfied if they had experienced an intervention
than if they had not, but having experienced more total interventions was not
associated with lower grief or greater satisfaction with overall care; the latter
was related more to the attentiveness and sensitivity of health care personnel.
Three groups identified as in need of greater attention are clinic patients, who
were significantly less satisfied and more grief-stricken than the patients of
private physicians, those who had spontaneous abortions or ectopic pregnancies,
and those who had early fetal losses.
PMID- 10184044
TI - Distinguishing between cooperation and conspiracy. Swarthmore Radiation Oncology,
Inc. v. Lapes.
PMID- 10184045
TI - ERISA preemption rejected in suit by hospital for payment. Hoag Memorial Hospital
v. Managed Care Administrators.
PMID- 10184046
TI - Transfusion of blood contaminated by HIV raises consent issues. Jones v.
Philadelphia College of Osteopathic Medicine.
PMID- 10184047
TI - Court blocks discovery of application for medical staff privileges. Alexander v.
Superior Court (Saheb).
PMID- 10184048
TI - Trauma case reviews questioned.
PMID- 10184049
TI - Hospital surcharges preempted by ERISA. Travelers Insurance Co. v. Cuomo.
PMID- 10184050
TI - Health care providers are serious about savings through energy and building
management.
PMID- 10184051
TI - Nation's governors demonstrate art of compromise.
PMID- 10184052
TI - RSNA (Radiological Society of North America) participants embrace new imaging
standard. DICOM 3.0 promises easy healthcare imaging communications.
PMID- 10184053
TI - The provider's duty to a pregnant employee: court holds preferential treatment
not required. Armstrong v. Flowers Hosp., Inc.
PMID- 10184054
TI - The role of the CFO in CQI. Panel discussion.
PMID- 10184055
TI - Supreme Court upholds preemptive powers of OSH Act. Gade v. National Solid Waste
Management Association.
PMID- 10184056
TI - Who's responsible for restraint? Jane & Joseph Doe v. State of New York.
PMID- 10184057
TI - Court rules on validity of bloodborne pathogen rule. American Dental Association
v. Martin.
PMID- 10184058
TI - Making strategic alliances work.
PMID- 10184059
TI - Primary care capacity. The HMO Group Conference.
PMID- 10184060
TI - Report of survey: pregnancy outcomes in medical laboratory technologists.
AB - A survey was published and distributed in the CSLT Bulletin. Completed surveys
were returned anonymously by mail. Of the surveys returned (n = 2002), 16 were
not usable due to incomplete information. Spontaneous abortion (SA) occurred in
19.9% of the total responders' pregnancies. Technologists not employed during
pregnancy had a lower rate of SA (13.2%) compared to those working full-time
(19.9%) (p < 0.001). Including all types of early (< 28 wk) pregnancy
terminations (except induced abortion) the non-employed group had a 17% incidence
of fetal loss compared to 23% in the group employed full-time (p < 0.001). The
differences in SA rate could not be accounted for by mother's age at pregnancy
nor previous obstetric history. The incidence of cesarean section was higher in
the full-time employed group (16%) compared to the non-employed group of
technologists (9.9%) (p < 0.001). There were 141 reported birth defects
representing an overall incidence in responders of 4.8%, comparable to literature
values for the general population (6.0%). The incidence of specific birth defects
was not different in the working group.
PMID- 10184061
TI - California Supreme Court recognizes limits on physicians' disclosure obligation.
Arato v. Avedon.
PMID- 10184062
TI - Potential vaccines raise ethical, logistical, and economic concerns.
AB - Several years ago, central questions in the AIDS research field were: Is it
possible to develop a vaccine against HIV? If so, when, and what strategies show
the most promise? Now, even with no safe and effective vaccine in the pipeline,
attention is nonetheless shifting towards potential problems associated with
selecting the populations most in need of the product, conducting the clinical
trials, and delivering the vaccine in a fair and equitable manner. These problems
were the focus of a session at the annual meeting of the American Association for
the Advancement of Science (AAAS), held in San Francisco in February. The
following articles summarize two of the presentations at the session.
PMID- 10184063
TI - IPAs and PHOs may vanish with capitation.
PMID- 10184064
TI - Configuring services for community needs.
PMID- 10184065
TI - Organizing integrated delivery systems: practical business, legal, financial
issues.
PMID- 10184066
TI - From involvement to results: 10 secrets of successful market-based strategic
planning.
PMID- 10184067
TI - Restructuring health care delivery: effective strategies for implementation.
PMID- 10184068
TI - Integrated health care systems: a consultant's lessons learned from the field.
PMID- 10184069
TI - HMOs demand better hospital deals as markets shift to managed care.
PMID- 10184070
TI - Meeting proves groups, chains wield enormous buying power.
PMID- 10184071
TI - Quality versus variance: a plea for a different focus and terminology.
AB - Much has been written about quality assurance in medical practice over the past
15 years. Medicine suddenly found itself trying to design systems that ensured
that medicine was being practiced according to standards of quality when it had
neither a definition of its product nor defined standards of practice.
Consequently, early quality assurance programs focused primarily on documentation
of patient care. As the process matured, it evolved to generic screens, with
tolerances and outliers. The theory was that the quality of medical care was
enhanced by physicians who practiced within often artificially established norms
and was diminished by physicians who practiced outside those same norms. It was
much like saying that the quality of manufacturing a new car could be improved by
reducing all systems down to one of closely standardizing, observing, and
documenting how each individual assembly worker put on a lock nut and then
holding each worker independently accountable for the final quality of the care.
Physicians felt they were being held responsible for conforming to a rigid set of
poorly designed and retrospectively applied standards. Moreover, they were held
accountable for applying those standards to all practice situations.
Understandably, physicians felt at the mercy of nonphysician quality assurance
"detectives" in hospitals and became increasingly suspicious of nurses and
administrators, who were perceived as abusing the system at the expense of the
physicians. Because of these inadequacies of the earlier quality assurance
programs, paranoia among physicians about the quality assurance process remains
rampant today. The use of blind outcome scores and practice patterns in
credentialing and the reporting of these data to databanks have reinforced the
paranoia.(ABSTRACT TRUNCATED AT 250 WORDS)
PMID- 10184072
TI - Subacute care. Medical and rehabilitation definition and guide to business
development. American Health Care Association.
PMID- 10184073
TI - Controversies in home respiratory care, Part I. Based on a conference held
October 29-31, St Petersburg Beach, Florida.
PMID- 10184074
TI - Controversies in home respiratory care: conference summary.
PMID- 10184075
TI - Demographics and financial impact of home respiratory care.
AB - Healthcare policymakers, governmental and private alike, are now faced with an
enormous challenge. Demands for improved access to cost-effective and high
quality healthcare are emanating from all segments of our society. Clearly, the
traditional model of admitting patients to an acute care hospital as a first-line
intervention is losing favor. Although there will always be a role for acute
hospital care, utilization of this high-cost setting must be better managed if
runaway healthcare costs are to be brought under control. The concept of moving
patients along the healthcare continuum as their response to treatment reduces
the acuteness of their condition is rapidly gaining support, especially with
third-party payors. Accordingly, home healthcare providers, including those
offering respiratory home care services, can expect to see an increase in the
number of referrals they receive. HME/RT providers must actively promote the
benefits they can offer in terms of high quality, cost-effective outcome. It is
not unrealistic to suggest that the savings realized by reducing an acute
hospital stay by 1 day can easily cover the costs of providing respiratory home
care for 4 to 6 weeks. One can only hope that such compelling arguments,
occurring at a time when healthcare reform and restructuring is a national
priority, will translate to more equitable reimbursement guidelines for
respiratory home care providers. The past practice of only reimbursing for
equipment and supplies fails to take into account the vital role played by the
home respiratory therapist. Home respiratory equipment and supplies, while an
important component of managing chronic respiratory disease, are only effective
if used safely, properly, and in compliance with the prescribing physician's
intentions. The use of skilled and dedicated home respiratory therapists to train
patients, monitor and assess outcomes, and communicate with the prescribing
physician ensures optimum results. It is time for reimbursement policies to
recognize this vital role played by home respiratory therapists.
PMID- 10184076
TI - Current and future role of respiratory care practitioners in home care.
PMID- 10184077
TI - Novel strategies for delivering oxygen: reservoir cannula, demand flow, and
transtracheal oxygen administration.
AB - Oxygen-conserving devices can decrease costs because less oxygen is used.
However, they may also add costs due to the more complex equipment involved (ie,
device and catheter replacement). Oxygen is relatively expensive. To decrease the
cost of oxygen therapy, conserving devices must decrease the frequency of home
deliveries and/or the number of cylinders used. By promoting mobility and
improving adherence to continuous oxygen therapy, oxygen-conserving systems may
increase the amount of oxygen used, thus offsetting savings. It is shortsighted
to focus only on reducing the costs of oxygen administration. Attention also
needs to be directed to patient outcomes such as functional status, use of
healthcare services, and quality of life.
PMID- 10184078
TI - Center-based vs patient-based diagnosis and therapy of sleep-related respiratory
disorders and the role of the respiratory care practitioner.
AB - Unlike center-based laboratories that follow prescribed technical standards,
patient-based studies lack technical standardization. Whereas center-based
studies are usually performed by technicians who have met certain professional
criteria, patient-based studies can be performed by anyone, even those without
clinical training. Although guidelines are currently being developed to direct
the use of unattended monitoring in the home, a need exists for specific
guidelines that delineate professional qualifications for those who initiate and
titrate therapy for patients with sleep-related respiratory disorders. The
opportunity exists for respiratory care practitioners to become involved with
creating guidelines for patient monitoring and therapeutic intervention, in both
center-based and patient-based settings. A need exists for multicenter, peer
reviewed, controlled studies to establish standard recording variables and
machine specifications for unattended monitoring devices. Also, the role and cost
benefit ratio of unattended monitoring in healthcare delivery need to be defined.
Therefore, with the demand for technology-oriented research, clinical outcome
studies, and professional standards, more respiratory care practitioners have the
opportunity to expand their practice into the field of sleep medicine.
PMID- 10184079
TI - Respiratory protection: any answers out there?
PMID- 10184080
TI - Federal support for application of the Americans with Disabilities Act to medical
staff decisions. The Medical Society of New Jersey v. Jacobs.
PMID- 10184081
TI - The Texas PPO cases: a harbinger of managed care turmoil to come? Texas Medical
Association v. Aetna Life Insurance Co., Texas Medical Association v. Prudential.
PMID- 10184083
TI - U.S. Supreme Court rules on actionable gender discrimination. Harris v. Forklift
Systems, Inc.
PMID- 10184082
TI - Should patient dumping statute be used to support 'right to life' position? In
the matter of Baby "K".
PMID- 10184084
TI - Social Security tax due for student nurses. Johnson City Medical Center v. United
States.
PMID- 10184085
TI - Status of agreement for professional services reviewed. Ransburg v. Haase.
PMID- 10184086
TI - Legal justification for licensure of pharmacy technicians. Mace v. Charleston
Area Medical Center.
AB - OBJECTIVE: To review the facts and legal rationale of a lawsuit in which a
hospital was held liable for discharging a pharmacy technician from employment.
SUMMARY: The hospital and the pharmacy technician previously had disagreed about
several matters. The technician believed he was being discriminated against based
on his need to be away from work to serve in the National Guard. On one occasion,
the technician reported to work in what appeared to be a drug-impaired state. The
technician subsequently was discharged from employment. He sued, contending that
the discharge was in retaliation for his asserting his rights as a National Guard
member. The technician won the lawsuit. CONCLUSIONS: Employment law bends over
backward to protect employees. When an employee is not licensed, the only
effective peer review is within the employment relationship. The public may not
be effectively protected from harm that might be caused by employees who are not
competent. Strong laws that protect employees restrict the ability of employers
to oversee employee conduct. Therefore, for employees whose incompetence may pose
a threat to the public, licensure provides a necessary additional level of
protection.
PMID- 10184087
TI - Group purchasers join forces to save dollars.
PMID- 10184088
TI - Loss prevention colloquy III, held March 10-11, Deerfield Beach, FL.
PMID- 10184089
TI - Sponsors envision new directions for healthcare ministry.
PMID- 10184090
TI - Rubber windmill: power to the people.
AB - The fourth Rubber Windmill simulation exercise highlighted some interesting
issues--among them that managers will be under more pressure and CHCs should have
more power. Margaret Martin, Head of Public Information Services at East Anglian
RHA, reports.
PMID- 10184091
TI - Rethinking EMS. After Sand Key, things will never be the same.
PMID- 10184092
TI - Keeping promises. Townsend v. Catalina Ambulance Co. Inc.
PMID- 10184093
TI - Legislative forum: participating in healthcare reform.
PMID- 10184094
TI - Definitions in paediatric palliative care.
AB - Consideration of care provision for children with life-threatening and life
limiting illness may be hampered by the lack of an agreed set of working
definitions for such basic terms as: child, life-threatening condition, life
limiting condition, palliative care, respite care and hospice care. We suggest
definitions to stimulate debate, and hopefully agreement, about terms that are
central to the Department of Health's current programme of pilot initiatives in
support of children with life-threatening and life-limiting illnesses, and their
families.
PMID- 10184095
TI - The future of the long-term care leader. ACHCA Young Leaders Forum, February
1993.
PMID- 10184096
TI - Biological products; blood specificity designators; technical amendments--FDA.
Final rule; technical amendments.
AB - The Food and Drug Administration (FDA) is amending the biologics regulations to
correct certain omissions from the designators for blood specificities and make
other minor, technical amendments. This action is being taken to clarify and
improve the accuracy of the regulations.
PMID- 10184097
TI - As different as snowflakes. With Alzheimer's, the best approach is to recognize
that each patient is unique.
PMID- 10184098
TI - Lab coalition pushes its reform agenda. American Association for Clinical
Chemistry.
PMID- 10184099
TI - ACS/CDC meeting explores risks of blood-borne pathogens.
PMID- 10184100
TI - Health care reform terms and approaches.
PMID- 10184101
TI - Acute care hospitals: prepare for the boomers.
PMID- 10184102
TI - Chaos offers opportunity for creativity.
PMID- 10184103
TI - Rural hospitals hard-hit by rise in AIDS cases.
PMID- 10184104
TI - Catholic execs talk of affiliations while keeping sense of mission.
PMID- 10184105
TI - The illusion of quality.
PMID- 10184106
TI - Mother's prenatal records discoverable in malpractice suit brought by child.
Palay v. Superior Court; Grosslight v. Superior Court.
PMID- 10184107
TI - Court recognizes limits on disclosure of alternative treatment. Moore v. Baker.
PMID- 10184108
TI - Courts examine use of peer review documents. Young v. Saldanha; Ashokan v.
Nevada.
PMID- 10184109
TI - Innovative devices expanding laparoscopy.
PMID- 10184110
TI - The buzz on reform.
AB - Mr. Bouchard bravely travels through the maze of lingo and anagrams spawned by
recent attempts at healthcare reform. This comprehensive list of terminology and
definitions, which provides considerable detail and analysis, will be invaluable
to anyone trying to understand current trends.
PMID- 10184112
TI - Draft uniform data set for home care and hospice. National Association for Home
Care.
PMID- 10184111
TI - Four views of managing change.
PMID- 10184113
TI - Laboratory test ordering, costs, and delivery options highlighted at recent
conferences.
PMID- 10184114
TI - Successful new medical technology ventures will need to show value. MIT
Enterprise Forum of the Northwest.
PMID- 10184115
TI - Computer assisted serum/biological fluid storage: hemophilia serum/plasma bank.
AB - Samples are drawn from hemophiliacs to retrieve plasma and serum for testing and
storage. The samples for testing are tested and the results compiled using a
database computer program. The samples for storage are coded and stored at -70
degrees C under controlled conditions. The location of the samples is then
entered into the database computer program. The results of the tests, or the
stored sample location, can be easily retrieved using the computer.
PMID- 10184116
TI - Hospitals increase satisfaction and reduce costs by redesigning around patients.
Workforce reengineering.
PMID- 10184117
TI - Market forces for health service courses.
PMID- 10184118
TI - Nursing error not the cause of delay of correct patient diagnosis. Gill v.
Foster.
PMID- 10184119
TI - Informed consent does not require physician to disclose statistical life
expectancy data to cancer patients. Arato v. Avedon.
PMID- 10184120
TI - Husband of patient must pay for unwanted medical treatment. Grace Plaza of Great
Neck, Inc., v. Elbaum.
PMID- 10184121
TI - Assessing the physician's standard of care when HIV is transmitted during
artificial insemination. Ter Neuzen v. Korn.
PMID- 10184122
TI - Riggins v. Nevada: The accused's right to "just say no" to antipsychotic drugs?
PMID- 10184123
TI - A case of wrongful use of quality management. Summit Health, Ltd., v. Pinhas.
AB - Summit Health, Ltd., v. Pinhas liberalized the jurisdiction of the Sherman
Antitrust Act to include cases of intrastate hospital credentialing. The U.S.
Supreme Court decision eased the requirements for plaintiffs to sue when they
perceived that health care organizations were acting as monopolies. The court
removed the defense that a plaintiff had to prove that the decision of a health
care organization affected interstate commerce for the case to be heard in court.
Important as the case is in antitrust law, however, greater lessons can be gained
by health care organizations from analyzing the events that led to the lawsuit.
PMID- 10184125
TI - Impressions of the 1994 Healthier Communities Summit.
PMID- 10184124
TI - ACS conference links investigators and NIH.
PMID- 10184127
TI - What to look for before you sign a contract.
PMID- 10184126
TI - Health care for adolescents: developing comprehensive services.
PMID- 10184128
TI - Integrating IM practices: is bigger better?
PMID- 10184129
TI - Becoming a 'preferred provider'.
PMID- 10184131
TI - Capitation: prepare for the knock on the door.
PMID- 10184130
TI - Getting paid what you're worth.
PMID- 10184132
TI - A time to lead: shaping your community's healthcare future. 79th Annual Catholic
Health Assembly, June 5-8, 1994, Philadelphia.
PMID- 10184133
TI - Self-care, values lead to healthy communities.
PMID- 10184134
TI - Goal-oriented advocacy essential in healthcare reform.
PMID- 10184135
TI - Picking up the pace of improvement.
PMID- 10184136
TI - Malpractice, informed consent, and physician relationships interwoven in
Louisiana decision. Riser v. American Medical International.
PMID- 10184137
TI - Court rejects withholding ventilator treatment from an anencephalic infant. In
the Matter of Baby K.
PMID- 10184138
TI - Capitated supply pacts: still more questions than answers.
PMID- 10184139
TI - Minimally invasive surgery technology: highlighted at Clinical Congress of
American College of Surgeons.
PMID- 10184140
TI - Glimpse of new, cost-effective, environmentally conscious technologies exhibited
at the RSNA (Radiological Society of North America).
PMID- 10184141
TI - New options for balancing cost vs. quality of high-technology radiology
equipment.
PMID- 10184142
TI - Conference hears promising developments from AIDS researchers.
PMID- 10184143
TI - Growth of minimally invasive surgery tied to economics: highlights from the
Clinical Congress of American College of Surgeons, Part II.
PMID- 10184144
TI - Trio gives N.Y. a mixed message.
PMID- 10184145
TI - Health care reform based on money, not care.
PMID- 10184146
TI - AHA reports 31% profit increase.
PMID- 10184148
TI - Joint Commission forum explores surveys.
PMID- 10184147
TI - AHA Dallas convention brings votes to focus on systems in long term, allow
'independents' as trustees.
PMID- 10184149
TI - Health care in the courts. Airedale NHS Trust v. Bland.
PMID- 10184150
TI - Assistive algorithms for exposure management: Part I: Chickenpox, scabies, and
lice.
PMID- 10184151
TI - Local voices. Allied powers.
PMID- 10184152
TI - Quantum leap.
PMID- 10184153
TI - Drug management, cost issues, educational strategies, changing marketplace top
agenda.
PMID- 10184154
TI - Insurance company forced to pay for autologous bone marrow transplant. Leonhardt
v. Holden Business Forms Co.
PMID- 10184155
TI - Court establishes procedures for withdrawing life support. In re Martin.
PMID- 10184156
TI - Ruling on nurses' status clarifies labor issue. National Labor Relations Board v.
Health Care & Retirement Corp. of America.
PMID- 10184157
TI - The Estates Environment Forum for the NHS in Scotland and Northern Ireland.
PMID- 10184158
TI - The rural agenda for healthcare reform.
PMID- 10184159
TI - Reforms must restructure care delivery, healthcare experts insist.
PMID- 10184160
TI - Comment: "Do not resuscitate order" allowed for an infant with AIDS: In the
Interest of C.A.
PMID- 10184161
TI - Petrillo and its progeny: the Illinois judicial ban on ex parte communications in
medical malpractice cases comes under fire.
PMID- 10184162
TI - Comment: Gilbert v. Sycamore Municipal Hospital: Illinois adopts apparent agency
expanding hospital liability for negligent physicians.
PMID- 10184163
TI - Capital views: highlights of perspectives in medical management 1994.
AB - Washington, D.C., where health policy is currently being debated, served as an
appropriate backdrop May 4-7 for the College's annual "Perspectives in Medical
Management" conference. Some of its federal buildings served as classrooms for
those interested in learning the legislative process through participation in the
"Health Policy Institute," which was held simultaneously. Although it is
impossible to report on all that transpired during the four-day conference, this
article will briefly describe the comments of a few of the speakers.
PMID- 10184164
TI - Therapist-driven protocols: the state of the art.
PMID- 10184165
TI - The widening sweep of the ADA: court favors obesity claim.
PMID- 10184166
TI - Provider group execs vary on key elements of integrated systems.
PMID- 10184167
TI - Contrast compensates for slow flow in MRA.
PMID- 10184168
TI - Development of an Australian drug utilisation database: a report from the Drug
Utilization Subcommittee of the Pharmaceutical Benefits Advisory Committee.
PMID- 10184169
TI - Classification of active medical devices according to the Medical Device
Directive.
AB - Under the Medical Device Directive, manufacturers must group their products into
four classes--I, IIa, IIb, and III--classification being based on the degree of
risk the device presents. To aid manufacturers in the application of the
classification rules of the Directive, especially with regard to the combination
of active and nonactive characteristics, this article provides a guideline that
includes definitions and a reduced scheme for the combined characteristics of
these devices.
PMID- 10184170
TI - Principles of risk management.
AB - The steps of risk management are outlined, together with a range of the most
useful tools. Risk management involves hazard and risk identification, assessment
(quantitative or nonquantitative or both), risk reduction and risk control.
While the techniques were developed in military and industrial applications, they
are entirely applicable to transfusion medicine, and are particularly appropriate
in ensuring that the low probability of serious adverse effects remains low and
is further reduced.
PMID- 10184171
TI - First peptide agent enters clinical arena.
PMID- 10184172
TI - Integrated multisensor technology: biosensors for the future.
PMID- 10184173
TI - Dynamic three-dimensional echocardiography: methods and clinical potential.
AB - In this article, we will attempt to review basic requirements for three
dimensional reconstruction, methods of cavity reconstruction, approaches to gray
scale tissue-depiction displays, and current clinical experience, and also
present some directions for future development.
PMID- 10184174
TI - Elevation of hemoglobin, MCH, and MCHC by paraprotein: how to recognize and
correct the interference.
PMID- 10184175
TI - The impact of pharmacoeconomics on the practitioner and the patient: a conflict
of interests?
AB - It is very easy to polarise the debate between clinicians and economists by
asserting that clinicians regard the needs of individual patients as paramount,
whereas economists are more interested in the priorities of society as a whole.
Economists have criticised clinicians for failing to recognise the scarcity of
resources relative to wants and also for being unable to appreciate the diversity
of individual preferences. Furthermore, economists will assert that the wants of
patients are not the same as their needs. A clinician may use degree of illness
as a guide to relative need for treatment, whereas an economist would ask for
information about response to treatment, explicitly acknowledging that the most
severely ill patient may not derive the greatest benefit from treatment. We
believe that the key to this problem lies in the differences in the definition of
terms by the 2 sides, and in fact that there is some confusion over the primacy
of the individual versus society. Both clinicians and economists are liable to
assert that healthcare resources should be distributed equitably. However,
clinicians have a somewhat imprecise appreciation of the concept of equity,
whereas economists have developed a set of explicit definitions of equity, which
clearly show the consequences of shifting the balance of resources to achieve
equitable distribution. Inevitably, this leads to diversion of resources from one
segment of society to another. At present, any transfer of resources is liable to
be viewed as a sacrifice of an individual patient's needs in the interests of
society as a whole. This paper shows that clinicians already accept that there
is a conflict of interests between the wants of individuals and the needs of
society. We believe that progress can only be made by increasingly explicit
debate about the merits of different treatments. Economists have developed the
theoretical framework; it is up to clinicians to turn theory into practice.
PMID- 10184176
TI - Decisions program looks to regionalization.
PMID- 10184177
TI - Foresight + shared control = success, says AHA chair-elect.
PMID- 10184178
TI - Courts rule on treatment refusal. In the matter of the involuntary discharge or
transfer of J.S. by Ebenezer Hall.
PMID- 10184179
TI - How do we know?
AB - Home care personnel working with physicians meet with terms every day that may
not be clear to them. In an effort to preclude misinterpretations, mistakes, or
time expended trying to clarify instructions, this article covers some of the
terminology that might occur in physician orders, on records, or in the medical
literature.
PMID- 10184180
TI - Employers beware: you may be bound by the terms of your old employee handbooks.
Robinson v. Ada S. McKinley Community Services, Inc.
PMID- 10184181
TI - Visions--today's trends, tomorrow's possibilities. Roundtable discussion.
AB - What do today's customers really want. How are foodservices responding? What's
hot in purchasing, forecasting and technology? These are the key topics addressed
by 12 industry leaders when they gathered recently in Chicago.
PMID- 10184182
TI - Supreme Court strikes down National Labor Relations Board's restrictive
definition of health care supervisor. N.L.R.B. v. Health Care & Retirement
Corporation of America.
PMID- 10184183
TI - Supreme Court strikes blow at health care unions. NLRB v. Health Care &
Retirement Corp.
PMID- 10184184
TI - Physician-assisted suicide: pros and cons of first federal case. Compassion in
Dying v. Washington.
PMID- 10184185
TI - Glossary of terms.
PMID- 10184186
TI - Obesity recognized as a handicap under Rehabilitation Act. Cook v. State of Rhode
Island.
PMID- 10184188
TI - Medicare reimbursement denied for complimentary meals for staff physicians.
Wilmot Psychiatric/Medicenter Tuscon v. Shalala.
PMID- 10184187
TI - Evidentiary ruling favorable to physician. Palinkas v. Bennett.
PMID- 10184189
TI - Recovery for emotional distress from fear of AIDS rejected. Carroll v. Sisters of
St. Francis Health Services.
PMID- 10184190
TI - Bond requirements struck down by Florida Supreme Court. Psychiatric Associates v.
Siegel.
PMID- 10184191
TI - Oregon court rejects "captain of the ship" doctrine. Holger v. Irish.
PMID- 10184192
TI - Use of defective medical device raises questions. Blythe v. Radiometer America,
Inc.
PMID- 10184194
TI - Another opinion: reallocation, not reform needed.
PMID- 10184193
TI - The new health care. Report from the Strategic Marketing Leadership Forum reveals
initiatives of forward-thinking marketers.
PMID- 10184195
TI - Hospital foodservices prepare for tougher times.
PMID- 10184196
TI - Highlights from the Classification Symposium.
PMID- 10184197
TI - Raising quality in the NHS: progress. Conference held 17 November 1993.
PMID- 10184198
TI - The resurgence of nature-speak.
AB - In contemporary bioethics, two vocabularies can be distinguished: person-speak
and nature-speak. The first is built around the claim that a person's moral
decisions are to be respected, while the other stands on the claim that moral
decisions should comply with standards for human behaviour conveyed by nature.
While most bioethicists have obtained a thorough mastery of person-speak, they
are considerably less well-versed in nature-speak. Apparently, the latter has
lost much of its former ability to capture important aspects of moral existence.
In this paper I attempt to rehabilitate nature-speak from a hermeneutical
perspective. I believe that the task of ethics is to enlarge our range of moral
description and to rediscover neglected ways of speaking about human experience.
The ethicist should enable individuals in health care settings to become more
articulate about their moral experience. He should not content himself with
applying those moral vocabularies which happen to be readily available, but
should rather proceed by recovering forgotten vocabularies from within the
philosophical tradition. Finally, one particular effort at restoring nature-speak
is critically reviewed.
PMID- 10184199
TI - Health care in the courts. Frenchay Healthcare NHS Trust v S.
PMID- 10184200
TI - Are true primary care givers overlooked?
PMID- 10184201
TI - Community-based delivery.
PMID- 10184203
TI - Court refuses to reinstate chief of staff fired by hospital board. Keane v. St.
Francis Hospital.
PMID- 10184202
TI - Boundaries of relevant geographic market crucial to monopolization claim.
Morgenstern v. Wilson.
PMID- 10184205
TI - Requirements for reverse employment discrimination claim clarified. Harding v.
Gray.
PMID- 10184204
TI - Potential for hospital liability in consent context explored. Urban v. Spohn
Hospital.
PMID- 10184206
TI - Premier puts new teeth into contract compliance.
PMID- 10184207
TI - Partnering: know yourself first.
PMID- 10184208
TI - The state of the pandemic: the 10th Annual AIDS Conference.
PMID- 10184209
TI - Comment: Serving the patient, or self-serving? Nesseim v. Mail Handlers Benefit
Plan and health insurance plan interpretation.
PMID- 10184210
TI - How hospitals are luring doctors onto their payrolls.
PMID- 10184211
TI - Glossary of terms used in managed care. Managed Care Assembly, Medical Group
Management Association.
PMID- 10184212
TI - Primary-care docs get more Medicare money--Vladeck.
PMID- 10184214
TI - Panel asks who gains in hospital mergers.
PMID- 10184213
TI - Columbia/HCA's Scott cites need to change missions.
PMID- 10184215
TI - The first step toward a health assessment: define the community.
PMID- 10184216
TI - Change and opportunity in ambulatory care.
AB - Non-inpatient care is assuming greater importance within the Australian health
system. The management of the delivery of health services is becoming a
responsibility of clinicians. Clinicians, nurses, managers and academics need to
come together to advance these issues. This paper outlines the thinking at Monash
Medical Centre, a new 747-bed tertiary hospital situated in the south-eastern
suburbs of Melbourne.
PMID- 10184217
TI - CIO focus: integration & focusing on the customer.
PMID- 10184218
TI - Reform report: can healthcare revive a dying plan?
PMID- 10184219
TI - Columbia/HCA tries to "right-size" markets.
PMID- 10184220
TI - Employers may alter or terminate promised retiree health benefits, says 4th
Circuit. Gable v. Sweetheart Cup Co.
PMID- 10184221
TI - State associations' roundtable focuses on survival strategies.
PMID- 10184222
TI - Firm has new recipe for bonding more closely with fewer clients. RSNA convention.
PMID- 10184223
TI - The bioethics mega-meeting: a nonscientific analysis.
PMID- 10184224
TI - Marmor calls for separating sense from nonsense in reform debate.
PMID- 10184225
TI - Conference explores spiritual dimensions of illness and suffering.
PMID- 10184226
TI - The word "bioethics": its birth and the legacies of those who shaped it.
AB - Extensive historical sleuthing reveals that the word "bioethics" and the field of
study it names experienced, in 1970/1971, a "bilocated birth" in Madison,
Wisconsin, and in Washington, D.C. Van Rensselaer Potter, at the University of
Wisconsin first coined the term; and Andre Hellegers, at Georgetown University,
at the very least, latched onto the already-existing word "bioethics" and first
used it in an institutional way to designate the focused area of inquiry that
became an academic field of learning and a movement regarding public policy and
the life sciences. A further comparison of the Potter and the
Hellegers/Georgetown understandings of bioethics and the relative acceptance of
the two views will appear in the March 1995 issue of this journal.
PMID- 10184227
TI - Lovelace cuts costs, expands network and improves payer communication.
PMID- 10184228
TI - California peer reviewers are shielded from paying physician's attorneys' fees.
Mir v. Charter Suburban Hospital.
PMID- 10184229
TI - Sole area hospital may exclude nurse anesthetists in favor of physician
anesthesiologists. BCB Anesthesia Care, Ltd. v. The Passavant Memorial Area
Hospital Association.
PMID- 10184230
TI - New Geisinger II health care organizations tax-exemption test is no improvement
on prior model.
PMID- 10184231
TI - Court rejects physicians' challenge to hospital policy. Austin v. Mercy Health
System Corporation.
PMID- 10184232
TI - Hospital's wellness center denied exemption. Appeal of Sioux Valley Hospital
Association.
PMID- 10184233
TI - AmeriNet report echoes boom in alternate site purchasing.
PMID- 10184234
TI - Expense reduction on front burner at '94 MLI (McFaul & Lyons, Inc.) conference.
PMID- 10184235
TI - GPOs driving headlong toward fork in the road.
PMID- 10184236
TI - Developing hospital wide information management plans: librarians can be key
facilitators. Rochester Area Librarians in Health Care.
PMID- 10184237
TI - Hospital fund raisers face new paradigms. Association for Healthcare
Philanthropy.
PMID- 10184238
TI - Managed care: new practice frontiers.
PMID- 10184239
TI - Health system reform: a never-ending saga?
PMID- 10184240
TI - Reducing the need and demand for medical services.
PMID- 10184241
TI - Cancer care symposium tackles issues of change.
PMID- 10184243
TI - What do our customers need? A summary of the HLS/FLS panel discussion in San
Antonio.
PMID- 10184242
TI - Medical and clinical audit on online databases.
PMID- 10184244
TI - Conceptual model for longitudinal electronic record of diabetic patient.
PMID- 10184245
TI - Nurse practitioners sponsor women's health conference.
PMID- 10184246
TI - The Middle East total quality management conference.
AB - The Middle East conference on the implementation of the total quality management
(TQM) system in medical centers took place November 30 to December 2, 1993, in
Jerusalem. The conference was designed to assist health care providers in their
efforts to improve efficiency and effectiveness. It was also an opportunity for
professionals from the area to meet and exchange ideas with the intention of
creating a forum for continued cooperation.
PMID- 10184247
TI - Court orders EPA to promulgate medical waste incinerator regulations under
section 129 of the Clean Air Act. Natural Resources Defense Council, Inc. v. U.S.
Environmental Protection Agency.
PMID- 10184248
TI - Achieving successful integration.
PMID- 10184249
TI - DeRoyal forum: lively debate fuels capitated supply pact fire.
PMID- 10184250
TI - How leaders can create adaptive, energetic organizations.
PMID- 10184251
TI - How patient exams for insurers can boomerang.
PMID- 10184252
TI - Federal Circuit Court reinstates claim that Americans with Disabilities Act
applies to certain health plans. Carparts Distribution Center, Inc. v. Automotive
Wholesaler's Association of New England.
PMID- 10184253
TI - The HIV-infected health care provider. Doe v. Attorney General of the United
States.
AB - Doe demonstrates that once an employer enters into a relationship with an
individual and thereafter determines that he or she may be disabled, the employer
has the right to ask the individual questions about the possible disability when
those questions are relevant to assessing his or her qualifications for
continuing on the job. In fact, once a health care provider is on notice that an
employee's or physician's disability may render the employee or physician no
longer qualified, thereby potentially endangering patients, the provider is
required to determine whether the person is qualified for the job. In these
sensitive matters, employers must draw a fine line between unreasonably following
up on every rumor on the one hand, and on the other hand investigating reliable
information when there may indeed be a direct threat to patients.
PMID- 10184254
TI - Chicago cardinal warns of takeover by for-profits.
PMID- 10184255
TI - Panel scrutinizes masks, counts, and sterile prep sets.
PMID- 10184256
TI - Should this doctor go to prison?
PMID- 10184257
TI - Trademark attorneys enlist pharmacists in the battle to prevent medication
errors.
PMID- 10184258
TI - Execs advised against JCAHO alternatives.
PMID- 10184259
TI - Health plans make case for rational, responsible rationing.
PMID- 10184260
TI - Observations on the technology exhibits: CLMA's 1994 annual conference.
PMID- 10184262
TI - Looking at corporate decisions with an ethical lens.
PMID- 10184261
TI - Conference points out conflicts between purposes in suffering.
PMID- 10184263
TI - Punitive damages allowable for record alteration. Moskovitz v. Mt. Sinai Medical
Center.
PMID- 10184264
TI - Wrongful death suit not precluded by prior malpractice suit. Thompson v. Wing.
PMID- 10184265
TI - $5.1 million award in credentialing case upheld. Purgess v. Sharrock.
PMID- 10184266
TI - EMTALA does not apply to telephone conversations. Miller v. Medical Center of
Southwest Louisiana.
PMID- 10184267
TI - Disease management: a systems approach to managing health outcomes.
PMID- 10184268
TI - Medicare and GAAP: understanding the decision of the Sixth Circuit in Guernsey
Memorial Hospital v. Secretary of Health and Human Services.
AB - The Medicare Act entitles qualified providers to reimbursement for the
"reasonable cost" of furnishing hospital services to Medicare beneficiaries. The
Sixth Circuit's decision in Guernsey Memorial Hospital demonstrates the tension
between generally accepted accounting principles and Medicare reimbursement
principles.
PMID- 10184269
TI - An introduction to capitation.
PMID- 10184271
TI - Denial of reimbursement to hospital upheld. South Davis Community Hospital, Inc.
v. Department of Health.
PMID- 10184270
TI - Working with business coalitions. Price isn't the only factor.
PMID- 10184272
TI - Eighth Circuit Court of Appeals upholds assignment. Lutheran Medical Center v.
Contractors, Laborers, Teamsters and Engineers Health and Welfare Plan.
PMID- 10184273
TI - Physician-patient privilege is preserved in workers' compensation proceedings:
Morris v. Consolidated Coal Co.
PMID- 10184274
TI - ERISA plan administrator's denial of coverage for treatment provided to unborn
child not within pre-existing illness exclusion: Foster v. State Farm.
PMID- 10184275
TI - Indiana court declines to impose strict products liability on health care
provider for defective pacemaker. St. Mary Medical Center, Inc. v. Casko.
PMID- 10184277
TI - Microsoft chief Gates sees large window of opportunity in healthcare.
PMID- 10184276
TI - Death of insured no bar to tort cause of action for bad faith denial of coverage
of medical treatment. Weatherly v. Blue Cross Blue Shield Insurance Company.
PMID- 10184278
TI - 1995 Food Management Presidents' Forum.
PMID- 10184279
TI - Symposium proceedings: Educating for quality services management.
PMID- 10184280
TI - Imaging world shows DICOM standard works.
PMID- 10184281
TI - Kaiser using advertising to build brand loyalty.
PMID- 10184282
TI - Managed care organizations: an introduction--Part II of II.
PMID- 10184283
TI - Clinical database management: new skills for familiar functions.
PMID- 10184284
TI - HCFA expects big savings from new claims system.
PMID- 10184285
TI - Physician hospital organization.
PMID- 10184286
TI - Tales from the front: 'compliance with JCAHO standards doesn't necessarily make a
facility better or safer'.
PMID- 10184287
TI - A sore winner loses. Nicholson vs. Lucas.
PMID- 10184288
TI - Pennsylvania court rules on institutional relationships in damages context.
Kashner v. Geisinger Clinic.
PMID- 10184289
TI - U.S. Supreme Court reviews tests for determining when a nurse is a supervisor.
NLRB v. Health Care and Retirement Corporation of America.
PMID- 10184290
TI - Florida court rules in favor of insureds. Psychiatric Associates v. St. Paul Fire
& Marine Ins. Co.
PMID- 10184291
TI - Survival moves for the next three to five years.
PMID- 10184292
TI - Bringing soul to the workplace.
PMID- 10184293
TI - Nurses, surgeon not negligent in retained instrument suit. Kissinger v Turner.
AB - Instrument counts are controversial. Though they are recommended on all
procedures by the Association of Operating Room Nurses, the majority of hospitals
aren't doing them, according to a survey by OR Manager. What happens if you don't
have a policy, an instrument is left in, and the case goes to court? What is the
role of professional recommendations? The health care law firm of Horty, Springer
& Mattern discusses just such a case.
PMID- 10184294
TI - Jury verdict of $6.875 million in punitive damages for wrongful death affirmed by
Alabama Supreme Court. Atkins v. Lee.
PMID- 10184295
TI - Suspension of privileges to perform cardiovascular surgery. Giannelli v. St.
Vincent's Hospital and Medical Center of New York.
PMID- 10184296
TI - The Delta Dental case: "Fair procedure" comes to managed care. Delta Dental Plan
of California v. Banasky.
AB - All providers contemplating managed care contracts, both individual and
institutional, should carefully review the health plans' internal administrative
review and dispute resolution procedures before making their decisions,
especially if the contracts will represent significant income for the provider.
While there may be judicial recourse in California and in other states that adopt
the holding in Delta Dental, in other states providers may well be held to the
health plans' internal administrative decisions as a matter of contractual
agreement. Health plans should also review their own policies and procedures for
adequacy under applicable state law. The health care community will not know the
full extent of Delta Dental's implications until later cases area decided, but
for now it seems certain that another wave of change in this area is just
beginning.
PMID- 10184297
TI - Summary judgment in sexual harassment action overturned. Kopp v. Samaritan Health
System, Inc.
PMID- 10184298
TI - Administrative law judge rules on medical necessity of Medicare patient's
ambulance transportation. In the matter of Henry L.R.
PMID- 10184299
TI - Perspectives. Market forces cutting costs; long term effects unknown.
PMID- 10184300
TI - The need for a universal definition of nursing.
PMID- 10184301
TI - Managed care comes to rural markets.
PMID- 10184302
TI - Sorting out a meaning for a confusing buzzword.
AB - Proponents of object-oriented technology tout it as the key to creating a new
breed of computerized patient records. This approach to programming is said to be
more flexible and powerful than traditional procedural programming. But sorting
out just what a vendor means when using the term object-oriented can be
confusing.
PMID- 10184303
TI - Industry heads in uneasy truce. Ownership summit.
PMID- 10184304
TI - Not-for-profit leaders undaunted by summit.
PMID- 10184305
TI - Progress in geriatric care.
PMID- 10184306
TI - Health education.
PMID- 10184307
TI - Workers' compensation.
PMID- 10184308
TI - Rethinking healthcare delivery at HIMSS.
PMID- 10184309
TI - Up and running: HIM professionals and the computer-based patient record.
PMID- 10184310
TI - Discovery of witness' HIV status allowed to show bias. United States v. Morvant.
PMID- 10184311
TI - Why this doctor won $6 million from his hospital.
PMID- 10184312
TI - A ruling that may help you win more UR disputes. Hand vs. Tavera.
PMID- 10184314
TI - Execs advised to ignore lawyers, act in best interest of company.
PMID- 10184313
TI - Biosensors: where do we go from here?
AB - In the 1980s, researchers predicted that biosensors would dominate hospital POC,
POL, and home testing. While that hasn't quite come to pass, here's what
biosensors have accomplished and a look at their future.
PMID- 10184315
TI - VHA sees operating income fall, revenues, membership increase.
PMID- 10184317
TI - Product liability implications of biomaterials in the United States.
PMID- 10184316
TI - Biocompatibility evaluation of laser-induced AAm and HEMA grafted EPR. Part 1: In
vitro study.
AB - Samples based on ethylene-propylene rubber (EPR) have been surface grafted with
acrylamide (AAm) and 2-hydroxyethyl methacrylate (HEMA) using CO2-pulsed laser as
a stimulation source. Scanning electron microscopy (SEM), energy dispersive X-ray
analysis (EDXA) and attenuated total reflectance infrared (ATR-IR) spectra were
performed on the modified samples. These techniques revealed the formation of
grafted poly(AAm) and poly(HEMA) on the surface of EPR. The surface grafted
poly(AAm) and poly(HEMA) were found to have a fractal type of morphology. EDXA
showed insignificant grafted AAm and HEMA in regions where fractals were absent.
Fractal patterned surfaces provide hydrophilic and hydrophobic sites, making EPR
suitable as a biomaterial. In-vitro adhesion and spreading of alveolar
macrophages (AMs) cultured on the surface of modified samples have been evaluated
by hemocytometry and SEM, respectively, and compared with unmodified controls.
Relationships between AM adhesion and their spreading, with surface morphology,
graft level and water compatibility are also discussed. Generally, more AMs
attach onto unmodified surfaces with a greater degree of spreading, than on the
modified EPR. Samples grafted between 0.7 mg/cm2 and 1 mg/cm2 showed fairly low
AM density compared with both unmodified EPR and lightly modified samples (less
than 0.2 mg/cm2). AMs cultured on the unmodified EPR were larger and displayed
pronounced ruffling of the plasma membrane, an increased capacity for adherence
and spreading on the surface, and an increased number of extensive filopodia.
Moreover, AMs attached onto the surface of modified samples appeared rounded,
with minimal cytoplasmic spreading and ruffling.
PMID- 10184319
TI - Food for the 21st century. Report from ADA.
PMID- 10184318
TI - Levodropropizine (LD) activity in allergic asthmatic patients, challenged with
ultrasonically nebulized distilled water, metacholine and allergen-induced
bronchospasm.
AB - The antitussive compound Levodropropizine (LD) is active in animal
bronchoconstriction induced by histamine and capsaicin and in man protects from
bronchoconstriction induced by capsaicin. The primary objective of this study was
to evaluate the mechanism of action of LD given at 60 mg t.i.d. as oral drops,
for 8 days by means of specific bronchial challenges (allergens) and of aspecific
challenges acting via different receptors and fibers (i.e. metacholine via
cholinergic receptors and ultrasonically nebulized distilled water (UNDW) via
histamine and neuropeptide release). The study design is randomized, double
blind, cross-over versus placebo in 30 allergic asthmatic patients. Baseline
bronchial tone and bronchoconstrictor response to metacholine (MCh) were not
modified by active treatment nor by placebo. On the contrary, in airway
responsiveness to UNDW, the active treatment showed an antagonist effect against
induced bronchoconstriction of 59% [activity ratio (AR) as antilog = 0.41; 95%
confidence interval 0.35-0.54; p < or = 0.05] in comparison to no effect for
placebo. Similarly, in airway responsiveness to specific allergen, active
treatment antagonized the bronchoconstrictor effect of grass pollen by 83% and of
various allergens (dermatophagoides and grass pollen) by 72%, i.e. AR of 0.17
(95% confidence interval 0.045-0.65; p < 0.01) and of 0.28 (95% confidence
interval 0.07-1.04; p < 0.05), respectively. No antagonist effect was evident
with placebo at all times. Besides inhibiting cough, LD is also partially
effective in inhibiting bronchial hyperreactive response against specific
allergen and UNDW bronchoconstriction. Hence, LD might act by partly inhibiting
histamine and neuropeptide release.
PMID- 10184320
TI - Soy intake key to reducing coronary disease.
PMID- 10184321
TI - Making the most of capitation.
PMID- 10184322
TI - Rethinking radiology services.
PMID- 10184323
TI - Genie genie.
PMID- 10184324
TI - Distributor wants to rid materials management vocabulary of "just-in-time" and
"stockless".
PMID- 10184325
TI - How managed care is roiling internal medicine.
AB - Doctors at the American College of Physicians; annual meeting could talk about
little else. We gathered advice there for surviving the marketplace turmoil. We
also conducted a poll on job satisfaction (page 31).
PMID- 10184326
TI - San Antonio Forum issues, questions, advice & challenges.
PMID- 10184327
TI - Virginia court rules informed consent claim should have gone to jury. Rizzo v.
Schiller.
PMID- 10184328
TI - Court denies summary judgment to hospital in physician's discrimination suit.
Alexander v. Rush North Shore Medical Center.
PMID- 10184329
TI - Handling items obtained from the search and inventory of a patient's clothing.
Flowers v. New Britain General Hospital.
PMID- 10184330
TI - AORN reaffirms its position on RN circulators.
PMID- 10184331
TI - In the matter of Baby K: implications for hospital administration.
PMID- 10184332
TI - 1995 International Hospital Symposium for Efficient Energy Use, held February 15
17, Basel, Switzerland.
PMID- 10184333
TI - Increasing the autonomy of "old souls".
PMID- 10184334
TI - Electronic integration a must for integrated delivery networks.
PMID- 10184335
TI - Panel urges creation of Boston system.
PMID- 10184336
TI - Managed healthcare congresses: a pharmacist's view.
PMID- 10184337
TI - In the Matter of Juveniles A, B, C, D, E: analyzing the rights of individuals by
junkyard standards.
PMID- 10184338
TI - Resuscitation in acute care hospitals--the time for change is now!
PMID- 10184339
TI - Conference calls for change in emergency research standards.
PMID- 10184341
TI - 2nd State of the Art Conference on Methods in Phase I. Bron, France, February 9
10, 1995. Abstracts.
PMID- 10184340
TI - New "Group of 100" meets with ACS Advisory Council for Surgery.
PMID- 10184342
TI - Supreme Court rejects longstanding labor rule for nurses. NLRB v. Health Care &
Retirement Corp. of America.
AB - This past year, the Supreme Court significantly changed the rules regarding
whether nurses are entitled to unionize, strike, and engage in other concerted
activities under the National Labor Relations Act (NLRA). Health care employers
may now lawfully deny NLRA rights to any nurse that assigns or responsibly
directs the work of other employees in a manner that requires the use of
independent judgment. Accordingly, health care employers will need to revise
their labor relations policies and implement well-informed litigation strategies
for defending their decision making in light of the Supreme Court's ruling.
PMID- 10184343
TI - Supreme Court upholds policy governing losses on advance refundings. Shalala v.
Guernsey Memorial Hospital.
PMID- 10184344
TI - TMA/THA conference. Rural physicians and administrators share experiences in
managed care.
PMID- 10184345
TI - Drug misuse. The searchers.
PMID- 10184346
TI - European healthcare. Continental shift.
PMID- 10184347
TI - Crusade continues for patient-centered care.
PMID- 10184348
TI - Catholic group bans for-profits.
PMID- 10184349
TI - Court denies relief to excluded chiropractor. Petrocco v. Dover General Hospital.
PMID- 10184350
TI - Record of joint counseling session not privileged in subsequent litigation
between the participants. Redding v. Virginia Mason Medical Center.
PMID- 10184351
TI - Excluding immigrants on the basis of health: the Haitian Centers Council decision
criticized.
PMID- 10184352
TI - Haitian Centers Council, Inc. v. Sale: rejecting the indefinite detention of HIV
infected aliens.
PMID- 10184353
TI - King v. Collagen Corporation: FDA approval insulates medical device manufacturers
from state common law liability.
PMID- 10184354
TI - Change leads to improvement: pediatric asthma and breast cancer care.
PMID- 10184355
TI - Going by the book at HHS. Shalala v. Guernsey Memorial Hospital.
AB - A recent U.S. Supreme Court decision upheld HCFA's authority to make important
reimbursement policy through informal Medicare manuals. The ruling has far
reaching implications for health care providers.
PMID- 10184356
TI - To be or not to be: waiving informed consent in emergency research.
PMID- 10184357
TI - The government's best offense is deference: the decision of the Supreme Court in
Shalala v. Guernsey Memorial Hospital.
AB - The United States Supreme Court agreed with the Secretary of Health and Human
Services that Guernsey Memorial Hospital's advance refunding transaction costs
would be subject to a medicare reimbursement policy that is not based upon
generally accepted accounting principles. According to the sharp dissent in this
case, this policy, set forth in a manual provision, contradicts federal
regulations.
PMID- 10184358
TI - The case of Baby K: exploring the concept of medical futility.
PMID- 10184359
TI - Providing rehabilitative services in rural communities: report of a conference.
AB - Rural communities have a disproportionate need for rehabilitative services,
partly attributable to an aging population and higher incidence of occupational
injuries. Despite increased need, many rural communities find rehabilitative
services unavailable due to personnel shortages, maldistribution of health care
personnel, and related recruitment and retention issues. The National Rural
Health Association and the Division of Associated, Dental, and Public Health
Professions of the Health Resources and Services Administration co-sponsored a
conference to explore issues related to ensuring that rural communities have
access to vital rehabilitation services provided by allied health professionals.
The status of rehabilitative care in rural settings and the barriers to
improvement in services delivery were described by consumers, providers,
educators, and public and private agency representatives. Recommendations
directed to state and federal authorities, educational institutions, and
professional organizations centered around increasing the supply of appropriately
trained allied health providers. Improving retention of rehabilitative personnel
in rural areas could be achieved by specific changes to the practice climate.
PMID- 10184360
TI - The case for a new medical cohort: teliatrics.
AB - Although medical specialities exist for the branches of medicine concerned with
the extremes of the life span (neonatology, pediatrics, adolescent medicine and
geriatrics), no such attention has been directed to the characteristic medical
conditions of adults in their prime, ages 45-64. Based upon the justification
that such a cohort should be identifiable demographically and chronologically as
well as clinically significant, the Baby Boom Generation (those individuals born
between 1946 and 1964) deserves considerably more attention than it has received.
The expected growth and clinical importance of this cohort over the next 20 years
will be significant for health care policy makers and providers of health care
services. This paper discusses the realities of this notable cohort and
introduces a new word to describe this group more scientifically. Words, derived
from Latin and Greek, are used extensively in the medical literature and provide
much of the foundation for clinical nomenclature. The word is teliatrics,
introduced here to complement the current medical nomenclature.
PMID- 10184361
TI - Guidelines offer bulwark against cost containment.
PMID- 10184362
TI - Underwriting psychiatric impairments, with emphasis on depression. Part II:
Treatment.
PMID- 10184363
TI - Health care in the courts. R v Gaud, Southwark Crown Court.
PMID- 10184364
TI - AHA annual meeting: Gingrich scolds AHA strategy, calls for new partnership.
PMID- 10184365
TI - United States Supreme Court rules against Medicare providers in cost
reimbursement case. Shalala v. Guernsey Memorial Hospital.
AB - In the long run, the impact of Guernsey will depend on the interpretation and
application of the decision by HCFA, the Provider Reimbursement Review Board, and
the courts. If HCFA interprets the decision as a signal that the Supreme Court is
willing to grant federal agencies broad latitude to avoid the rulemaking
requirements of the APA, providers may have fewer opportunities for formal input
into payment policy issues under the Medicare program. The impact of the case may
well go beyond cost-based reimbursement issues and affect all aspects of the
Medicare program.
PMID- 10184366
TI - California expands the duty to warn patients exposed to and infected with HIV.
Reisner v. Regents of the University of California.
AB - There is still no general definitive guide for hospitals and other health care
providers concerning the extent of their duty to warn third parties of a
patient's HIV status. However, even in states like California that have
statutorily eliminated any duty to directly inform third parties, the Reisner
case clearly indicates that liability to third parties may arise indirectly based
on a failure to warn HIV-exposed or -infected patients of their status and the
risks of communicating the virus to others. Accordingly, health care providers
should take several actions: 1. Ascertain, with the assistance of legal counsel,
the precise dictates of applicable state statutes and case law regarding (a) a
provider's obligation to warn HIV-exposed or -infected individuals of the
potential of communicating the virus to others; (b) additional statutory
requirements such as notification of public health authorities; and (c) whether
notice to third parties at risk of exposure from the patient is required or even
permitted. 2. Develop and implement written policies regarding notification and
counseling of exposed or infected patients, including counseling patients on the
risks of communicating the virus to third parties; and 3. Develop and implement
written policies regarding permissive or mandatory notification and counseling of
exposed or infected third parties. In this context, providers should be aware
that patient confidentiality and privacy laws may prohibit disclosure of the
identity of exposed or infected patients to third parties.
PMID- 10184367
TI - Patients' secrets and threats to third parties: where to draw the line. R. v.
Ross.
PMID- 10184368
TI - Patient's discharge linked to end of insurance coverage. Muse v. Charter Hospital
of Winston-Salem, Inc.
PMID- 10184369
TI - Geographic market definition critical to monopolization claim. Morgenstern v.
Wilson.
PMID- 10184370
TI - Eleventh Circuit affirms decision involving nurse who refused to care for an HIV
positive patient. Armstrong v. Flowers Hospital, Inc.
PMID- 10184372
TI - Stress Echo, 1st International Symposium. Pisa, Italy, 12-14 January 1993.
Abstracts.
PMID- 10184371
TI - Nursing Interventions Classification: a standardized language for nursing care.
AB - Although nurses constitute the largest single group of healthcare providers in
the United States, confusion exists about what nurses actually do. This article
provides an overview of the Nursing Interventions Classification (NIC), which is
the first comprehensive classification of nursing treatments. Quality management
professionals will find the NIC useful in designing quality management programs,
meeting Joint Commission standards, and planning redesign initiatives.
PMID- 10184373
TI - 4th Symposium on Aerosols and the Lung. Schmallenberg, Germany, April 15-16,
1994. Abstracts.
PMID- 10184374
TI - 1995 Healthier Communities Summit. A direction that we can go.
PMID- 10184375
TI - Optimize, ration care--Eddy.
PMID- 10184376
TI - 2nd International Conference on Sepsis in the ICU. Maastricht, The Netherlands,
27-29 June, 1995. Abstracts.
PMID- 10184377
TI - The Supreme Court's decision in New York State Conference of Blue Cross and Blue
Shield Plans v. Travelers Insurance.
PMID- 10184378
TI - A step toward first come, first served. Wagner v. Fair Acres Geriatric Center.
PMID- 10184379
TI - Utah state property tax exemption litigation concluded. Howell v. County Board of
Cache County.
PMID- 10184380
TI - NAPH (National Association of Public Hospitals) gears up to battle impending
cuts.
PMID- 10184381
TI - Healthcare recruiters receive survival tips.
PMID- 10184382
TI - Mastering skills of "virtual" integration is key.
PMID- 10184383
TI - Dealing with the demands of change.
AB - If evidence of the changes occurring in and confronting the health care field
were needed, it was provided in abundance at the College's Perspectives in
Medical Management meeting in Chicago in May. The presentations and the
discussions among members buttressed the feeling that the health care field is
proceeding through a period of transformation. The evolving system will be
anchored on managed care, with special emphasis on the word "managed." The
accoutrements of managed care--case management, demand management, utilization
management, clinical guidelines and protocols, capitation budgeting, and the like
-dominated discussion. The "business" of health care is proceeding apace.
Maintaining a balance between the financial and quality elements of health care
delivery has never been more important. And the definition of that balance will
be determined at the local and regional levels. Federal initiatives are
temporarily in abeyance. The challenge for physician executives is to assume
leadership in moving their organizations, and thus the health care system, toward
a new design that corrects present deficiencies and positions both to respond
more effectively to the health care market. While it is not possible to cover all
of the more than 60 speakers who addressed the meeting, this report, through
presentation of the ideas of some key presenters, is aimed at measuring at least
the boundaries of the challenges that lie ahead.
PMID- 10184384
TI - Conference tackles ethical issues in managed care.
PMID- 10184385
TI - Commentary on the standardization of terms and analytic methods.
PMID- 10184386
TI - Standardization of terms and analytic methods for performance evaluation:
achievable goal or impossible dream?
AB - Communication about health care management is severely limited by the usage of
words borrowed from the diverse professional groups that have contributed to the
field. This article suggests development of a glossary of terms to eliminate much
of the current confusion in discussions of outcomes, reduce redundancy, and form
the basis for interdisciplinary understanding. As a starting point, some major
concepts are discussed that warrant further refinement and definition. Also
highlighted is the need for standards in describing and evaluating systems
designed to measure outcomes of health care, with the goal of enabling consumers
to compare these systems meaningfully.
PMID- 10184387
TI - Refounding the ministry. Leadership in an era of profound change. The 80th
Catholic Health Assembly.
PMID- 10184389
TI - The 1994 National Health Information Forum.
PMID- 10184388
TI - Is this the year you'll sell your practice?
PMID- 10184390
TI - GOP won't reach goals for cuts in Medicare, ex-CBO chief says.
PMID- 10184391
TI - Can disposables keep their promises?
PMID- 10184393
TI - 3rd International symposium on Advanced Physiological Monitoring. Munich,
Germany, September 8-10, 1994. Abstracts.
PMID- 10184392
TI - Reflections on human spirituality for the worksite.
PMID- 10184394
TI - 15th International symposium on Intensive Care and Emergency Medicine. Brussels,
March 21-24, 1995. Abstracts.
PMID- 10184395
TI - Patient denied admission based on HIV status. Howe v. Hull.
PMID- 10184396
TI - Physicians fighting on new fronts. Levine v. Central Florida Medical Affiliates,
Inc.
PMID- 10184397
TI - Western governors' policy group lists barriers to telemedicine.
PMID- 10184398
TI - Aetna, Lee Memorial win Fla. deal.
PMID- 10184399
TI - AHA's new vision looks beyond word 'hospital'.
PMID- 10184400
TI - Paid attendance at AHA meeting falls to new low.
PMID- 10184401
TI - Grants to fund model networks.
PMID- 10184403
TI - Expanding our services. Reality strikes at Sand Key II.
PMID- 10184402
TI - Closed circuit anesthesia: the man-machine interface.
PMID- 10184404
TI - PACS terminology for the uninitiated. Vanderbilt University Medical Center.
PMID- 10184405
TI - Cost pressures won't subside, managers hear.
PMID- 10184406
TI - Strategies for negotiating preemployment agreements.
AB - Though the long-term effects of preemployment agreements on career development
are unknown, these guidelines are suggestions to ensure responsible interactions
among facilities, health information management students, and academic programs.
Preemployment agreements meet personal, educational, professional, financial, and
institutional goals. Long-term implications warrant additional study.
Preemployment agreements are increasing because they mutually benefit HIM
students and employers. This emerging process, however, is creating new ethical
and legal dilemmas for academic programs and other involved parties. The intent
of this article is to identify potential issues and dilemmas involved in student
employee negotiations and preemployment agreements. The issues and proposed
guidelines may not be germane to all situations. Many successful relationships,
primarily those that include the guidelines discussed here, have been negotiated.
Terminology for preemployment agreements is different from terminology for
financial aid. Consistent use of terminology, and knowledge regarding these
agreement processes including guidelines for their appropriate use, is necessary
to avoid ethical and legal problems. Exploration of the impact of preemployment
agreements on future career decisions and professional development is needed.
PMID- 10184407
TI - Techno jargon: a telecom technology primer.
PMID- 10184408
TI - CAMRT members accept degree requirement for entry to practice. Canadian
Association of Medical Radiation Technologists.
PMID- 10184409
TI - Supreme Court: state hospital rate laws trump ERISA. New York State Conference of
Blue Cross & Blue Shield Plans et al. v. Travelers Insurance Co. et al.
PMID- 10184410
TI - 8th World Congress on Emergency and Disaster Medicine. Stockholm, Sweden, 20-23
June 1993. Abstracts.
PMID- 10184411
TI - Symposium explores OR team efficiency.
PMID- 10184412
TI - Ohio hospital wins spot on key panel.
PMID- 10184413
TI - Reforms opening up Latin America.
PMID- 10184414
TI - What's in a name? The language of assisted living.
PMID- 10184415
TI - Marketplace reform and clinical integration. 13th Annual Malcolm T. MacEachern
Symposium, June 2, 1995.
PMID- 10184416
TI - Introduction, courtship, wedding, and family.
PMID- 10184417
TI - Medication errors. Automation holds promise of prevention.
PMID- 10184418
TI - Legal liability.
PMID- 10184419
TI - 9th World Congress on Disaster and Emergency Medicine. Jerusalem, Israel, 28 May
1 June 1995. Abstracts.
PMID- 10184420
TI - Abstracts of the thirteenth Southern Biomedical Engineering Conference.
Rockville, Maryland. April 16-17, 1994.
PMID- 10184421
TI - The Hanlester Appeal: the latest decision regarding physician self-referral joint
ventures.
PMID- 10184422
TI - The HMO Group Conference. Tobacco use prevention and reduction.
PMID- 10184423
TI - Biosensor markets: opportunities and obstacles.
AB - Currently, glucose sensing for the control of diabetes is the only high-volume
market for biosensors. Yet, a variety of lower-volume niches are available for
exploitation in medical diagnostics and the pharmaceutical and other industries.
There are problems waiting for biosensor solutions, but the balance between
market opportunities and technical and/or financial obstacles will control the
future expansion of biosensor technology.
PMID- 10184424
TI - Biosensors in critical care.
AB - Electrochemical bio/chemosensors are ideally suited to critical care situations.
Factors such as fast response, portability, minimal sample preparation, and lack
of need for highly trained staff reduce the time between testing and therapeutic
decision. In addition, the accuracy of these devices approaches that of more
traditional laboratory-based clinical analysers.
PMID- 10184425
TI - Case law involving base-station contact.
AB - INTRODUCTION: Although general discussion of legal claims against emergency
medical services (EMS) have been published, there is no literature that examines
legal claims that specifically have involved base-station contact for direct
medical control. METHODS: A review of case law through July 1994 was conducted to
identify cases that involved radio communications between a prehospital provider
and a physician or nurse under the direction of a physician. RESULTS: Only eight
cases could be identified. Each case is described in terms of the event, selected
pertinent legal issues, and the opinions rendered by the court. CONCLUSIONS:
These few cases illustrate some important observations that indicate that there
will occur an increase in the detail, role delineation, and clarification of the
prehospital providers, medical directors, base-station physicians, and others who
provide direct medical control to prehospital EMS providers. These findings have
important implications for EMS medical directors.
PMID- 10184426
TI - New York's highest court further defines physician's duty to patients. Aufrichtig
v. Lowell.
PMID- 10184427
TI - Hospital bound by fixed payment agreement with insurer. Nahom v. Blue Cross &
Blue Shield of Arizona.
PMID- 10184428
TI - Pennsylvania Supreme Court rejects hospital's immunity claim. Cooper v. Delaware
Valley Medical Center.
PMID- 10184429
TI - Optical biosensors. A bright future.
AB - Progress in fibre-optic technology, laser miniaturization, and the reproducible
manufacture of prisms and wave guides has made the commercial exploitation of
optical biosensors possible. Some optical biosensors are miniaturized versions of
traditional spectrophotometers, others are based on new integrated-optic methods.
This article reviews the achievements already made in this area and the
opportunities for the future.
PMID- 10184430
TI - Elder abuse policy: considerations in research and legislation.
AB - Elder abuse has become the most recently "discovered" form of intrafamilial
violence. Most states have enacted elder abuse statutes or have amended their
adult protection acts to specify the elderly. A majority of jurisdictions have
included mandatory reporting requirements within their statutes. Commentary has
been fiercely opposed to mandatory reporting for a variety of reasons. Compelled
reporting does not appear to increase the number of reports filed, while
enforcement of the schemes depletes much of the funds devoted to elder abuse.
Definitions of elder abuse are contradictory and vague. Mandatory reporting
requirements suggest that legislators believe elders are unable to determine
whether reporting is in their own best interests and thus is an ageist response
to the problem of elder abuse. Finally, few services are available to families in
which elder abuse has been verified and even fewer program evaluations have been
performed to assess these services. Mandatory reporting to identify elder abuse
is not appropriate in the absence of programs found to be helpful.
PMID- 10184432
TI - Federal court rejects ADA claims. McDaniel v. Mississippi Baptist Medical Center.
PMID- 10184431
TI - HIV-positive surgeon denied relief. Doe v. University of Maryland Medical System
Corp.
PMID- 10184433
TI - ADA complicates disciplining of employees with substance abuse problems.
PMID- 10184434
TI - Congress hears providers' Medicare wish list.
PMID- 10184435
TI - Glossary of terms used in managed care. Managed Care Assembly (MCA) of Medical
Group Management Association (MGMA).
PMID- 10184436
TI - International Congress on Aerosols in Medicine, in Health and Disease. November
23-26, 1994, Cairo, Egypt. Abstracts.
PMID- 10184437
TI - Where health care is headed now.
PMID- 10184438
TI - Will a plaintiff's attorney see your own medical records?
PMID- 10184439
TI - Wrongful resuscitation: getting sued for saving lives. Anderson vs. St. Francis
St. George Hospital.
PMID- 10184440
TI - Strengthening partnerships for quality: Quality Leadership Conference '95.
PMID- 10184441
TI - Pricing and reimbursement of pharmaceuticals: an evaluation of cost-containment
strategies. Proceedings of a symposium. Talloires, France, July 21-22, 1993.
PMID- 10184442
TI - The pros and cons of generic medicines.
PMID- 10184444
TI - Introduction to disaster management. Lesson 2--concepts and terms in disaster
management.
PMID- 10184443
TI - The National Association of State EMS Directors.
PMID- 10184445
TI - Clinical guidelines for delayed or prolonged transport. III. Spine injury. Rural
Affairs Committee, National Association of Emergency Medical Services Physicians.
PMID- 10184446
TI - Health care in the courts. R v Cambridge District Health Authority.
PMID- 10184447
TI - MGMA, in reversal, adds physicians to its board.
PMID- 10184448
TI - Terms with industry weight leave consumers, employers puzzled.
PMID- 10184449
TI - 1st International Meeting on Interventional Cardiology. Jerusalem, Israel, June
18-23, 1995. Abstracts.
PMID- 10184450
TI - The 9th annual conference and scientific assembly of the National Association of
EMS Physicians. Minneapolis, Minnesota, 10-13 June 1993. Abstracts.
PMID- 10184451
TI - In nearly complete legal 180, federal appeals court spares rural Wisc. IDS.
AB - After suffering two costly legal losses, a provider-owned rural Wisconsin
integrated delivery system under attack by one of the state's most powerful
payers has won a potentially sweeping legal victory. A federal appeals court has
rejected charges by Blue Cross & Blue Shield of Wisconsin and the Blues' HMO,
CompCare, that the Marshfield Clinic monopolized a 10-county market in north
central Wisconsin. The Wisconsin Blues took Marshfield to court early last year,
charging the clinic with controlling such a large section of the north-central
Wisconsin market that CompCare couldn't gain a foothold. A federal jury in
January agreed, slapping the rural IDS with a $48.5 million damage award for 19
counts of anticompetitive conduct. A federal district court judge later shrank
the damages--but did little to the verdict. Charles J. Steele, an antitrust
attorney with Washington, D.C.'s Foley & Lardner, explains what happened next.
PMID- 10184452
TI - FTC, Justice ask for clarification in Marshfield case.
PMID- 10184453
TI - Bioethics: from adolescence to mid-life crisis.
PMID- 10184455
TI - Managers face 'bumpy road' during rapid transition.
PMID- 10184454
TI - Managed care demands better OR efficiency.
PMID- 10184456
TI - International forum: The U.K. A forum discussion on circles of dependence of
quality in the blood transfusion community.
PMID- 10184458
TI - Integration taxonomy.
PMID- 10184457
TI - Anti-hepatitis C virus serology in patients affected with congenital coagulation
defects: a comparative study using three second generation ELISA tests.
AB - We determined the prevalence of anti-hepatitis C virus (HCV) antibodies in 34
patients affected with congenital coagulation disorders attending the Haemophilia
Centre of Padua, Italy. Serological tests were carried out by three second
generation enzyme linked immunosorbent assays (ELISA), two based on recombinant
proteins (Ortho and Abbott) and one based on synthetic peptides (Behring) as
antigenic substrate. The repeatedly reactive specimens were further assayed by
the supplemental 4-antigen recombinant immunoblot assay (RIBA) (Chiron and
Ortho). Moreover, we performed the dot-blot Matrix test (Abbott) on the samples
showing discrepant results by the three ELISA tests. Twenty-six patients (76.5%)
were anti-HCV positive using all three ELISA tests; 25 were confirmed by the
supplemental RIBA test, the other one was indeterminate. Two samples were in a
gray-zone only using the anti-HCV ELISA Abbott. These were positive by the RIBA;
in contrast, such samples showed no reactivity with the Matrix test. In
accordance with the current literature, these data show an equivalence between
the 2nd generation screening tests (ELISA), at least when applied to a high risk
population as in the present study. Further, these screening tests demonstrated a
reliable specificity, since most of the ELISA-reactive specimens were confirmed
by the supplemental RIBA test. In contrast, combined use of the anti-HCV tests
could be useful when high sensitivity is requested, as in the case of blood donor
pretransfusion screening.
PMID- 10184459
TI - New York court refuses to dismiss retaliatory action suit. Rodgers v. Lenox Hill
Hospital.
PMID- 10184460
TI - Disclosure of patient's treatment records without consent leads to licensing
board reprimand. Rost v. State Board of Psychology.
PMID- 10184461
TI - Minimizing due process problems in hospital corrective action proceedings. In re
Smith.
PMID- 10184462
TI - Ninth Circuit Hanlester decision adds another twist to anti-kickback statute.
PMID- 10184463
TI - Hospitals walk fine line when granting medical staff privileges. Candler General
Hospital v. Persaud.
PMID- 10184464
TI - Managed care organizations: fiscal responsibility vs. direct liability. Fox v.
Health Net of California.
PMID- 10184465
TI - Promina Symposium: Gingrich outlines MedicarePlus.
PMID- 10184466
TI - Reform over morals, not economics.
PMID- 10184467
TI - Tough delivery choices need to made.
PMID- 10184468
TI - Stage set for passage of reform in '94.
PMID- 10184469
TI - Health care must function more like rest of business.
PMID- 10184470
TI - Who's an FP--and why it matters.
PMID- 10184471
TI - HIMSS (Healthcare Information and Management Systems Society) meeting sees
explosive growth.
PMID- 10184472
TI - Integration: opportunities and issues for medical group practices.
AB - McManis Associates, a health care management consulting firm, recently gathered
several medical group practice leaders for an informal discussion of integration
and other key trends affecting medical groups. The goal of this "Forum for
Medical Group Practice Leaders" was to elicit candid discussion among a small
group of executives (who are in key positions in medical group practices),
identify some of the key strategic issues they are facing and encourage them to
share their opinions and experiences. The forum participants come from diverse
backgrounds, a wide range of geographic locations and many different types of
professional settings, including a single specialty medical group; independent,
physician-owned multispecialty groups; an integrated medical center with its own
hospital; the physician component of a large, integrated, multi-hospital system;
and the leadership of the Medical Group Management Association (MGMA). The
discussion was facilitated by Gerald L. McManis, president of McManis Associates,
Inc., Louis Pavia Jr., senior vice president, and F. Kenneth Ackerman Jr.,
FACMPE, principal associate with the management consulting firm. This article
provides a summary of the forum's proceedings, and the executive views and
opinions of some of the key issues and challenges facing medical group practices
today, including integration initiatives, governance, access to capital, critical
success factors for group practices, as well as trends and projections for the
future.
PMID- 10184473
TI - New definition eases conscious sedation protocol.
PMID- 10184474
TI - Perspectives. Doctors' quest for freedom leads back to market angst.
PMID- 10184475
TI - Arnett v. Dal Cielo: peer review confidentiality threatened by medical board
investigational subpoenas.
AB - If not modified or overturned on appeal, the Dal Cielo decision will very likely
have a significant negative impact on the ability of California's organized peer
review bodies to conduct frank, candid, and confidential peer review. Dal Cielo
appears to permit the Board to subpoena committee minutes, physician credentials
files, and live testimony whenever it determines that a physician should be
investigated. Further, the impetus for the Board's investigation might be little
more than a complaint from a single patient or even a disgruntled former employee
of the physician or hospital. Regardless of current and future decisions,
however, peer review bodies in California and other states operating under
similar court decisions still retain at least some limited means to protect the
confidentiality of their evaluative work. If, for example, a peer review body can
establish that an investigatory subpoena seeks irrelevant information, is based
upon little more than unsubstantiated rumor, or that the medical board has made
no efforts to obtain information from other available, non-privileged sources, it
may be able to convince a court that the subpoena is not supported by good cause.
Peer review organizations should thus consider challenging medical board
subpoenas in court to narrow their scope or establish that there is sufficient
need for them. If any peer review body is served with an investigatory subpoena
by a medical board requesting production of peer review information, it should
carefully assess applicable state confidentiality protections.(ABSTRACT TRUNCATED
AT 250 WORDS)
PMID- 10184477
TI - Buzzwords, acquisitions shaping healthcare I/T.
PMID- 10184476
TI - Commissioner v. Schleier: back to the drawing board on the taxation of employment
dispute recoveries.
AB - The Court's decision in Schleier leaves the taxation of recoveries arising out of
employment disputes, as well as many other types of disputes, in a state of
confusion. To be sure, employers and employees now know with certainty that
recoveries under the ADEA are not excludable from income under Section 104(a)(2).
Recoveries under other statutes, however, including the Fair Labor Standards Act
and the 1991 version of Title VII of the Civil Rights Act of 1964, are altogether
unclear after Schleier. In the absence of further guidance, employers should
consider adopting a more conservative approach to employment dispute settlements
by treating settlement payments as taxable income, subject to withholding and
employment taxes.
PMID- 10184478
TI - Innovative approaches to laboratory management. National Committee for Clinical
Laboratory Standards Annual Meeting, Chicago, March 29-April 1, 1995.
PMID- 10184479
TI - Transcatheter Cardiovascular Therapeutics, 7th Annual Symposium. Washington,
D.C., February 22-26, 1995. Abstracts.
PMID- 10184480
TI - Drug delivery to the lungs V. The Aerosol Society. December 15, 1994, London, UK.
Abstracts.
PMID- 10184481
TI - Finding a common ground between medicine and managed care.
PMID- 10184482
TI - The Federal balancing act: what happens without the net?
PMID- 10184484
TI - Court limits damage award to professional corporation. Anesthesiologists
Associates of Ogden v. St. Benedict's Hospital.
PMID- 10184483
TI - All the roads lead to better patient care. Views from Drs. Kahn, Lindberg.
PMID- 10184485
TI - Advances in diagnostic imaging displayed.
PMID- 10184486
TI - Gingrich, Bernardin address AMA's House of Delegates.
PMID- 10184487
TI - FTC on your back? Answer may be home-town judge.
PMID- 10184488
TI - Glossary. A guide to technology terms.
PMID- 10184489
TI - A look at cancer care payment issues and strategies.
PMID- 10184490
TI - Qui tam suits and the anti-kickback law: more developments. Pogue v. American
Healthcorp, Inc., et al.
PMID- 10184491
TI - Functional imaging: radiology looks deeper into heart, brain, and the future.
PMID- 10184492
TI - Maybe bigger isn't better after all.
PMID- 10184493
TI - 1996 Presidents' Forum. Panel discussion.
PMID- 10184494
TI - Antitrust verdict in Marshfield Clinic case still ominous.
PMID- 10184495
TI - Qualified privilege bars defamation suit. Bickling v. Kent General Hospital, Inc.
PMID- 10184496
TI - Terminated physician denied relief. Blank v. Chelmsford OB/GYN, P.C.
PMID- 10184497
TI - Systems thinking helps leaders handle change. Seeing patterns aids problem
solving.
PMID- 10184499
TI - Leaders ponder EMS future at national meeting.
PMID- 10184498
TI - Managed care's challenge: physician-system integration.
PMID- 10184500
TI - The "salary basis" test: deductions from accrued leave for partial day absence
upheld. Barner v. City of Novato.
PMID- 10184501
TI - Health-care lingo for the jargon-challenged.
PMID- 10184502
TI - Medicare overrides plan's coordination-of-benefits provisions.
PMID- 10184503
TI - Summary of ICD-9-CM Coordination and Maintenance Committee meeting.
PMID- 10184504
TI - After the ball--uh, the practice acquisition ... Brown v. St. Luke's Memorial
Hospital.
PMID- 10184505
TI - Hospital owes no duty to secure informed consent. Kelly v. Methodist Hospital.
PMID- 10184507
TI - Court denies summary judgment to hospital in Employee Polygraph Protection Act
suit. Lyle v. Mercy Hospital Anderson.
PMID- 10184506
TI - Summary judgment denied in body parts donation suit. Perry v. Saint Francis
Hospital and Medical Center.
PMID- 10184508
TI - How David can survive Goliath ... a partnership survival strategy for community
based agencies.
PMID- 10184509
TI - SOS: standards of style. Style may vary.
PMID- 10184510
TI - Exploring the critical issues in infectious diseases. Symposium held March 17-19,
1995, in Santa Fe, New Mexico.
PMID- 10184511
TI - Implications for managed care organizations of the Merck and Medco consent.
PMID- 10184512
TI - Demand management moving to forefront.
PMID- 10184514
TI - Pa. not-for-profit system to subsidize local services.
PMID- 10184513
TI - The future of central service. ASHCSP's first videoconference.
PMID- 10184515
TI - Termination for speech in health care employment: when is discussion of health
care a matter of public concern. Rahn v. Drake Center.
PMID- 10184516
TI - Integration alone insufficient; focus on developing distinctness.
PMID- 10184518
TI - What Washington plans for doctors.
PMID- 10184517
TI - Effective resource management using a clinical and laboratory algorithm for chest
pain triage.
AB - BACKGROUND: Bridgeport Hospital recently compared the use of a clinical algorithm
with unaided physicians for the triage of 200 emergency department (ED) patients
with chest pain for coronary care unit (CCU) admission. HYPOTHESIS: Cardiac
troponin-T may be an effective adjunct to an established clinical algorithm for
accurate selection of patients who are admitted to the CCU for suspected acute
myocardial infarction (AMI). It is elevated 6 hours earlier than lactate
dehydrogenase fraction 1 (LD1) and may be the most effective test for confirming
non Q-wave AMI (usually with ST-T changes and LD1/lactase dehydrogenase > 35%).
It is elevated in class 3 angina with a high risk of fatal arrhythmia. STUDY
DESIGN: Clinical and electrocardiogram criteria for triage are as defined by
Goldman et al. (see references 6 and 11). The exclusion of non-AMI within 4 hours
of ED visit using troponin-T (or an alternative test) should allow more rapid
treatment of non-AMI patients at a lower intensity of hospital service (e.g.,
telemetry versus ICU). This should translate into shorter length of stay for non
AMI patients and facilitate thrombolytic therapy with significant resultant
medical and cost benefits. LABORATORY DATA: Creatine kinase and its MB isoenzyme
(CK-MB) are measured at the time of clinical triage and 4, 8, and 12 hours later.
LD1 and total lactase dehydrogenase are measured 12 hours after initial sampling.
Cardiac troponin-T is measured at the time of ED arrival and 4 hours later.
ANALYSIS OF BENEFIT: The first thing to consider is reducing the cost from stress
thalliums for low risk evaluation. The second is the evaluation of active
ischemia--unstable angina and diagnosis of missed AMI. The Goldman algorithm
eliminates unnecessary admissions to the CCU for chest pain, including unstable
angina. There is a difference between AMI and triage for CCU admission (200
patients). CK-MBs allowed for the elimination of 37 non-AMIs. However, we missed
eight cases of AMI that would have been LD1 positive (troponin positive) and
gained 10 cases of unstable angina that should have been assigned to CCU or a
monitored bed. Troponin found six more cases of unstable angina that were CK-MB
negative but should have been class 3 unstable angina that could be assigned to
at least a telemetry bed. This makes 14 cases of AMI or unstable angina
unaccounted for by CK-MB (5.6%). All of the cases were at risk of ventricular
arrhythmia within 36 hours. The only question was whether to assign them to CCU
or to monitored beds. The third point in the analysis is to examine the savings
in operating costs by substitution. The cost model, in selecting a strategy,
takes test costs, clinical outcomes, and the cost of clinical algorithms into
consideration.
PMID- 10184519
TI - LTC leaders learn to live with the "little darlings".
PMID- 10184520
TI - Aggressive marketing campaign saves Florida hospital. Tarpon Springs voters
reject city plan to sell hospital.
PMID- 10184521
TI - Managed-care group airs image concerns at meeting.
PMID- 10184522
TI - Lab-related findings from the Tenth International Conference on AIDS. An
unrelenting killer spreads worldwide.
PMID- 10184523
TI - The ADA at three years: a statute in flux.
AB - In the three years since the Americans with Disabilities Act (ADA) was enacted,
significant developments have occurred in the form of new administrative and
judicial interpretations of the Act. The new guidelines and decisions will assist
employers in complying with the ambiguous, and sometimes confusing, provisions of
the ADA. Recent developments in areas such as the definition of a disability and
the permissibility of medical inquiries, along with continuing developments in
the areas of mental disabilities and defining reasonable accommodations, give
employers insight into the obligations created by the ADA. These developments are
a good starting point to understanding the ADA, but there is still a long way to
go. This article surveys the recent developments in the law and examines the
considerations that have become important to the Equal Employment Opportunity
Commission and the courts in interpreting the ADA's provisions.
PMID- 10184524
TI - The 11th annual conference and scientific assembly of the National Association of
Emergency Medical Services Physicians. San Diego, California, 29-31 July 1995.
Abstracts.
PMID- 10184525
TI - Accounting and finance terms.
PMID- 10184527
TI - Decision draws attention to consent form language. Harris v. Tatum.
PMID- 10184526
TI - Defining the right to die.
PMID- 10184528
TI - Ninth Circuit rejects constitutional claims in Medicare exclusion case. Erickson
v. United States, ex rel. Department of Health and Human Services.
PMID- 10184529
TI - Texas Supreme Court examines role of on-call physician. St. John v. Pope.
PMID- 10184530
TI - Effect of exclusive contract once again confronted by a court. Garibaldi v.
Applebaum.
PMID- 10184531
TI - Nursing home settlement links clinical and billing data.
PMID- 10184532
TI - A look at providers who assume risk. Providers take charge in new capitated
arena. Panel discussion.
PMID- 10184533
TI - Behavioral healthcare: a rose by any other name.
PMID- 10184534
TI - "Dear patients: this is a most difficult letter to write".
PMID- 10184535
TI - Building bridges between the HMO and health services research communities.
Conference cosponsored by Group Health Association of America and Agency for
Health Care Policy and Research, San Diego, April 6-7, 1995.
PMID- 10184537
TI - U.S. healthcare piques interest abroad.
PMID- 10184536
TI - Instill a culture of change, hospital consultants advise.
PMID- 10184539
TI - Failure to offer diagnostic study leads to liability on consent theory. Martin v.
Richards.
PMID- 10184538
TI - A healthcare controlled vocabulary. A case is made for standardizing medical
terminology.
PMID- 10184540
TI - Court examines indemnification rights of former corporate officers. Neal v.
Neumann Medical Center.
PMID- 10184541
TI - Physician's duty to third parties examined. Pate v. Threlkel.
PMID- 10184542
TI - Will this doctor finally be vindicated?
PMID- 10184543
TI - Internist's antitrust claims rejected by Eleventh Circuit. Levine v. Central
Florida Medical Affiliates, Inc.
PMID- 10184544
TI - Silent PPOs are not PPOs.
PMID- 10184545
TI - Execs hear pleas for help with reform.
PMID- 10184546
TI - Speakers defend Catholic, for-profit ties.
PMID- 10184547
TI - VHA members reap benefits of savings.
PMID- 10184548
TI - 'New money' dominates bond issues.
PMID- 10184549
TI - Clinton, Reich rally SEIU's spirit.
PMID- 10184550
TI - The vocabulary of the World Wide Web.
PMID- 10184551
TI - Radiology department of the future.
PMID- 10184552
TI - Perspectives. DC seeks turnaround for fractured health system.
PMID- 10184553
TI - Hamburgers and hospitals: the case for standardization.
PMID- 10184554
TI - Strong relationships for physicians and executives. Recommendations for building
on common concerns.
PMID- 10184555
TI - Using a new classification for chronic hepatitis.
PMID- 10184556
TI - Subacute providers need survival skills to meet market shifts.
PMID- 10184557
TI - Making technology work for you.
PMID- 10184558
TI - Florida Supreme Court opens the door for patient's relatives to sue doctors.
PMID- 10184559
TI - Hospital conversions raise thorny issues.
PMID- 10184561
TI - CEOs see survival keys--strong niche, right partners, allied docs.
PMID- 10184560
TI - Women's subjective experience of hysterectomy.
AB - This paper presents data on the experience of hysterectomy from a sample of 656
women aged between 30 and 50 years recruited from patients of a random sample of
50 general practices in Perth. Respondents were identified as women who: had
undergone hysterectomy for reasons other than cancer; were affected by
gynaecological conditions; had neither gynaecological problems nor had undergone
hysterectomy. Respondents voluntarily completed a self-administered questionnaire
which covered demographic information, general health, gynaecological problems
and hysterectomy, sexual activities, and family relationships. Formal measures of
depression and self-esteem were included. The main concern was with the
psychological and social outcomes of hysterectomy rather than its physical
results. The findings showed that of 107 women who had undergone hysterectomy,
only two had negative comments about the outcome. There were significant effects
on both work and sexual relationships for women in the gynaecological condition
group, with 52 per cent reporting adverse effects on work and 46 per cent
believing that their sexuality was affected. Few women regarded the uterus as
'essential to femininity or womanhood' and very few saw it as affecting
sexuality. Women in the hysterectomy group reported that their satisfaction with
sexual activity had improved, whereas those with gynaecological conditions
believed that it had deteriorated. Depression and self-esteem scores were
significantly worse for women with gynaecological conditions.
PMID- 10184562
TI - A glossary of information systems terms.
PMID- 10184563
TI - Taking back health care. Doctors must work together.
PMID- 10184564
TI - Rehab group says: focus on patient needs across settings.
PMID- 10184566
TI - Evidentiary standard considered in feeding tube withdrawal decisions. In re
Tavel; In re Martin.
PMID- 10184565
TI - Court examines "reasonable accommodation" in nursing home admission context.
Wagner v. Fair Acres Geriatric Center.
PMID- 10184567
TI - Seeking substance at HIMSS '96 (Healthcare Information Management Systems
Society).
AB - A vast industry now exists to help you manage information overload.
Unfortunately, that industry tends to overwhelm with information about itself. We
asked technology writer Pete Wenzlick to sort out the real from the phony at the
nation's biggest health info-tech expo. Here is his report.
PMID- 10184568
TI - Decoding health language is key.
PMID- 10184569
TI - Enacting the new covenant: keeping faith with our tradition. The 81st Annual
Catholic Health Assembly.
PMID- 10184570
TI - Advanced Institute stresses personal assessment, spirituality.
PMID- 10184571
TI - How patients define "service".
PMID- 10184572
TI - Stem cells: what's happening? Workshops and symposia on the subject of
haematopoiesis.
PMID- 10184573
TI - System strategy. The siren call of the slogan.
PMID- 10184574
TI - Privatization not the answer--experts.
PMID- 10184575
TI - MD leadership key to managed care survival.
PMID- 10184576
TI - Fiduciary duty of corporate officer explored. Boston Children's Heart Foundation
v. Nadal-Ginard.
PMID- 10184578
TI - Physician's antitrust claims rejected. Levine v. Central Florida Medical
Affiliates.
PMID- 10184577
TI - Court rules no insurance coverage. Visiting Nurse Association v. St. Paul Fire &
Marine Insurance.
PMID- 10184579
TI - An analysis of Novak v. Cobb County Kennestone Hospital Authority. Eleventh
Circuit finds no liability for a hospital that sought court ordered blood
transfusion for a minor over his parents objection.
PMID- 10184580
TI - Courts deal with impaired physician issues. Altman v. New York City Health and
Hospitals Corp.; Ambrosino v. Metropolitan Life Insurance Co.
PMID- 10184581
TI - Court likely to decide Tenn. hospital's fate.
PMID- 10184582
TI - MR arthrography detects subtle joint pathology.
AB - In the inevitable cost-benefit analysis to come, the appropriate role of MR
arthrography will rightly be challenged. As arthroscopic and MR imaging
techniques become even more widespread and refined, a well-defined niche for MR
arthrography will eventually emerge.
PMID- 10184583
TI - Challenge tests to assess airway hyperresponsiveness and efficacy of drugs used
in the treatment of asthma.
AB - Bronchial provocation tests are useful to diagnose and assess severity of asthma
and to follow response to treatment. The tests used include those stimuli that
act "directly" on receptors causing contraction of airway smooth muscle, e.g.,
pharmacological agents, and those stimuli that act "indirectly" by causing
release of endogenous mediators that cause the airways to narrow. These
"indirect" stimuli include physical ones such as airway drying from hyperpnea and
changes in airway osmolarity from inhaling aerosols of water and hyperosmolar
saline. Indirect stimuli cause the airways to narrow in response to endogenously
released substances from inflammatory cells or nerves and responses are thought
to reflect the presence and severity of inflammation of asthma. Challenge with
hyperosmolar saline is now being used as an indirect test because it also
identifies persons with exercise-induced asthma and is appropriate to assess
suitability for diving with SCUBA. Hyperosmolar challenge is also useful to
assess the effect of both the acute and chronic treatment with antiinflammatory
drugs. This, combined with the potential to collect inflammatory cells in sputum
induced by the same stimulus should result in this challenge being more widely
used, not only in the hospital laboratory but also in epidemiology and
occupational asthma.
PMID- 10184584
TI - Purchasing silicone.
AB - Now that CE-marking of medical devices is in force, device manufacturers need to
be able to document that they employ the correct materials and components for a
particular application. To do this they need to understand exactly what they are
purchasing and show that their suppliers possess the necessary product range,
technical expertise, and, most importantly, the quality procedures required to
assure product integrity. This article sets out some basic definitions of
terminology relating to material specification and testing of silicone products.
PMID- 10184585
TI - After everyone leaves: preparing for, managing, and monitoring mid- and long-term
effects of large-scale disasters. 4-6 November 1994, Bloomington, Minnesota.
Proceedings.
PMID- 10184586
TI - Physician assisted suicide. Quill v. Vacco.
PMID- 10184587
TI - Methodist Hospital v. Physician Reliance Network: the emergence of antitrust
causes of actions relating to disease specific contracting.
PMID- 10184588
TI - Hospital liable for dumping although patient left before examination. Correa v.
Hospital San Francisco.
PMID- 10184589
TI - Recovering alcoholic physician not entitled to get old job back. Altman v. New
York City Health and Hospitals Corporation.
PMID- 10184590
TI - Failure to comply with state notification statute may be failure to warn. Harden
v. Allstate Ins. Co.
PMID- 10184591
TI - False Claims Act. Prefiling releases are invalid. United States ex rel. Pogue v.
American Healthcorp, Inc.
PMID- 10184592
TI - Proceedings of the Rome Conference on Interventional Cardiology. Rome, Italy.
June 13-15, 1994.
PMID- 10184593
TI - Why you should have been at the health lawyers' convention.
PMID- 10184594
TI - How health plans are fighting back.
PMID- 10184595
TI - Medicare and Medicaid programs; requirements for physician incentive plans in
prepaid health care organizations--HCFA. Final rule correction; notice of changes
in compliance dates, with comment period.
AB - In the March 27, 1996, issue of the Federal Register, we published, at 61 FR
13430, a final rule with comment period that implements requirements in sections
4204(a) and 4731 of the Omnibus Budget Reconciliation Act of 1990 that concern
physician incentive plans. In the preamble of that rule, we set forth dates by
which prepaid health plans had to comply with certain of the rule's provisions.
This document clarifies and changes some of those deadlines, and provides an
opportunity for public comments on them. It does not otherwise change the
requirements set forth in the rule. In addition this document corrects the March
27 rule's inadvertent reversal of the nomenclature change made by a previous
final rule.
PMID- 10184596
TI - The "right to die" in America: the Ninth Circuit's decision in Compassion in
Dying v. The State of Washington.
PMID- 10184597
TI - Blaming the messenger (model): antitrust challenges to physician-hospital
organizations.
PMID- 10184598
TI - A new look for the corporate practice of medicine doctrine: Berlin v. Sarah Bush
Lincoln Health Center.
PMID- 10184599
TI - Moving forward on 'ASCUS,' but not there yet.
PMID- 10184600
TI - 'A whole new era' in cardiac markers.
PMID- 10184601
TI - For Hemophilia Health CEO, work hits home.
PMID- 10184602
TI - Managed care perspectives in hormone replacement therapy.
PMID- 10184603
TI - Florida Fourth District Court of Appeals rejects Hanlester v. Shalala and finds
commission-based marketing contract violative of the Federal Medicare Anti
Kickback Statute.
PMID- 10184604
TI - New Jersey Appellate Court applies CON regulations retroactively.
PMID- 10184606
TI - Court rejects duty based on "informal consultation".
PMID- 10184605
TI - 14th Southern biomedical engineering conference, Shreveport, Louisiana, April 7
9, 1995. Abstracts.
PMID- 10184607
TI - One world. One hope. AIDS 11th International Conference Overview.
PMID- 10184608
TI - A special issue of abstracted articles on the management of change.
PMID- 10184610
TI - A multicentre prospective cohort study of immune function in patients treated
with monoclonally immunopurified or resin-purified SNBTS high-potency factor VIII
concentrate.
PMID- 10184611
TI - Recombinant factor VIIa (r-FVIIa) in haemophilia management.
PMID- 10184612
TI - Is industry's consumption of capital a healthy appetite?
PMID- 10184613
TI - Industry taking new look at medical error casualties.
PMID- 10184609
TI - Sertraline. A pharmacoeconomic evaluation of its use in depression.
AB - Depression is a common condition that is often unrecognised, misdiagnosed and/or
undertreated. It is associated with substantial direct, indirect and intangible
costs. The indirect costs of lost earnings/productivity and premature death
account for the majority of these costs; drug costs account for only about 1 to
2% of total costs and about 10 to 12% of direct costs. Thus, better recognition
and appropriate treatment of depression would increase the direct costs
associated with this illness, but would also have the potential to greatly reduce
indirect costs and consequently the overall cost of depression. Because of their
higher acquisition costs relative to tricyclic antidepressants (TCAs), there has
been much debate about whether the use of sertraline or other selective serotonin
reuptake inhibitors (SSRIs) for first-line treatment of depression can be
justified. While these agents have similar efficacy to TCAs, they are better
tolerated and have a lower risk of death on overdosage. Despite the large
economic burden of depression on society, pharmacoeconomic data on sertraline and
antidepressant drugs in general are scarce. Most of the available studies on
sertraline are limited to considerations of direct costs and do not assess costs
from a societal perspective. In addition, a number of studies have significant
methodological problems which limit determination of meaningful conclusions.
Nonetheless, data from 2 more recent studies with fewer methodological problems
than earlier studies indicated that sertraline was more cost-effective than TCAs
because of fewer psychiatrist consultations, and less costly than fluoxetine
because of fewer absences from work and fewer medical consultations. The cost
utility ratio of maintenance therapy of depression with sertraline appears to
fall within the range of accepted cost-utility ratios of common healthcare
interventions. Thus, studies to date have generally shown that overall treatment
costs with sertraline and other SSRIs are no greater than those for TCAs; this is
despite the lower acquisition costs of the latter agents. Therefore, it is clear
from these data that it is misleading to classify antidepressant agents as
expensive or inexpensive based solely on their acquisition costs. Sertraline,
therefore, can be considered as a first-line alternative to TCAs and other SSRIs
for the treatment of depression on both clinical and pharmacoeconomic grounds.
PMID- 10184614
TI - A successful methodology for improving the quality of clinical data.
AB - In search of accurate, timely, and consistent information, Kaiser Permanente's
Northern California Region set out to improve the quality of its clinical data.
Analysis of documentation patterns resulted in consistency of clinical data,
improved reimbursement, and a new dialogue between coding and medical staffs.
PMID- 10184615
TI - Scenes from Aspen.
PMID- 10184616
TI - Preemployment screening: what the record won't show. Kentucky Board of Nursing v.
Ward.
PMID- 10184617
TI - Art therapy. Creative solutions.
PMID- 10184618
TI - 15th Southern Biomedical Engineering Conference. Dayton, Ohio, March 29-31, 1996.
Abstracts.
PMID- 10184619
TI - How to speak EMS.
PMID- 10184620
TI - There's gold in them thar HILLS (Health Innovators Learning and Leadership
Summit).
PMID- 10184621
TI - Penrith paradoxes from analysis to synthesis II--the revenge. A report of the
symposium.
PMID- 10184622
TI - Is there a future for radical health promotion?
PMID- 10184623
TI - Will there be a philosophy of health promotion?
PMID- 10184624
TI - Electronic patient records: international developments.
PMID- 10184625
TI - Authorization issue pits providers against managed care organization. Pappas v.
Asbel.
PMID- 10184626
TI - Injunction against summary suspension vacated. Magrinat v. Trinity Hospital.
PMID- 10184627
TI - Landmark OR procedure studies lead the way for savings.
PMID- 10184628
TI - NAHAM's Regional Representative Transition Team meets in Chicago.
PMID- 10184629
TI - Data protection and confidentiality in health informatics. Handling health data
in Europe in the future. The Commission of the European Communities DG XIII/F
AIM. Proceedings of the AIM Working Conference, Brussels, 19-21 March 1990.
PMID- 10184630
TI - The Universal Medical Device Nomenclature System.
AB - To facilitate access to medical information, ECRI has developed and promulgated a
hierarchical medical device nomenclature system containing over 4,800 valid terms
and 3,100 cross-references. The Universal Medical Device Nomenclature System
(UMDNS) is appropriate for a wide range of applications. It is used world-wide
and is available in 5 languages (7 additional translations are in progress).
PMID- 10184631
TI - The CEN/TC 257/SC1-nomenclature.
AB - This report has been prepared to aid understanding of the decisions made by
CEN/TC 257/SC1-Coding systems and nomenclature for medical devices-in preparing
the following documents: prENV XXXX Nomenclature-Recommendations for an interim
system and rules for a future system, prEN YYYY Nomenclature-Specification for a
nomenclature system for medical devices for the purpose of regulatory data
exchange.
PMID- 10184633
TI - CEN/TC 251 medical informatics & EAN and HIBC coding.
PMID- 10184632
TI - Medical technology manufacturers' view of a European data exchange.
PMID- 10184634
TI - Medical device surveillance world-wide.
PMID- 10184635
TI - Computer-based medical terminology and knowledge representation.
AB - This paper briefly summarizes the characteristics of a computer-based medical
terminology constructed by the author. Its size is around 140,000, systematized
by meaning using a single attribute as key: similarity among instances covered by
the term. This systematization resulted in a single hierarchical tree. Initial
term typing was based on the knowledge patterns of the terms, represented by the
arcs (relationships) among terms (nodes). Six different types of medical terms
could be identified. For coding of a medical term, its position on the
hierarchical tree was used, the semantic address. It is recommended that the
semantic address should be used for worldwide compatibility.
PMID- 10184636
TI - Models for representation of terminologies and coding systems in medicine.
AB - Unification of medical coding systems is a perceived need involving a long-term
task. Standards will support convergence of present coding systems towards a
coherent set of tools. The Project Team "Model for Representation of Semantics"
(CEN/TC251/PT003-MOSE) modeled existing tools to obtain a vocabulary apt to
describe coding systems and terminologies. Requirements on faithfulness and
safety, usefulness and purposiveness, coherence and integration were worked out,
and the MOSE's 10 key principles for Standards in Medical Semantics were
established.
PMID- 10184637
TI - Two new efforts aimed at preventing errors.
PMID- 10184638
TI - America's latest export: managed care.
PMID- 10184639
TI - Medicine's most elusive goal.
PMID- 10184641
TI - IG's aide creates tempest over waivers for Medicare.
PMID- 10184640
TI - Family practice: how long can the good times roll?
PMID- 10184642
TI - Three's a crowd.
AB - Where do patients' rising expectations fit into the purchaser/provider
relationship? John Spiers, Harry Burns and Michael Richards look at this question
from a patient, purchase, and provider perspective.
PMID- 10184643
TI - Tutorial: causal modeling and patient satisfaction.
AB - Causal modeling is used in a variety of sciences because it allows exploration of
complex relationships among several variables simultaneously. Although not used
extensively in health care as yet, causal modeling could be helpful, given the
complexity of the current health care system. The purpose of this article is to
provide a general introduction to causal modeling and the syntax used in
developing and testing a model. To illustrate the method, a sample model is
tested using a combination of hypothetical and actual patient satisfaction data.
PMID- 10184644
TI - To need or not to need...
PMID- 10184645
TI - Broad view of necessary information in informed consent taken by Wisconsin court.
Johnson by Adler v. Kokemoor.
PMID- 10184646
TI - Incentives and the management of physician behavior in health service
organizations.
AB - The performance of a health services organization is affected by the cumulative
behavior of physicians out of proportion to their numbers or the economic value
of their services. Managers are challenged to optimize physician behavior and to
change it in concert with the evolving expectations of health service customers.
Incentives are the tools available for this effort. This article discusses the
interrelation of physician behavior, physician needs, and the major classes of
incentives: economic, noneconomic, and rules. While most organizations recognize
and use financial incentives, few utilize noneconomic incentives systematically.
Given the financial restrictions of advanced markets, managers should understand
the role of rules and the value of noneconomic issues to physicians when
developing incentive programs.
PMID- 10184647
TI - Likely effects of devolution on the redistributive character of policy agendas.
AB - This article assesses two competing views of the effects federal devolution may
have on the future of health, education and welfare programs in the United
States. One school of thought argues that devolution of social policy to the
state and local level will have negative consequences for the less affluent. A
contrasting view maintains that devolution will spur innovations at the state and
local level, which in turn will lead to more effective and efficient social
programs. Dileo analyzes presidential and gubernatorial speeches over a period of
5 years to assess the state of U.S. social policy. He concludes that the federal
government is generally more supportive of redistributive policies than are the
states.
PMID- 10184648
TI - Medical Informatics Europe'96. Human facets in information technologies.
Proceeding, Copenhagen, Denmark.
PMID- 10184649
TI - Antitrust protection extended to hospital authorities and physician peer review
participants. Crosby v. Hospital Authority of Valdosta.
PMID- 10184650
TI - Health care in the courts. Re C Family Division of the High Court, 3 April 1996.
Unreported.
PMID- 10184651
TI - Reservations are voiced about the reuse of single-use items.
PMID- 10184652
TI - Patient access to medical records.
AB - The issue of, and access to, medical records has been a contentious matter for
some years in Australia. The recent High Court decision of Breen v Williams has
clarified the law nationwide. The High Court confirmed that the ownership of
medical records is vested in the creator of the records. The High Court further
held that a patient has no right at law to access his or her medical records in
the absence of any statute granting such a right, or other legal process.
PMID- 10184653
TI - IFHRO coding quality workshop.
PMID- 10184655
TI - Medicine meets virtual reality. Health care in the information age. Proceedings
of Medicine Meets Virtual Reality 4. San Diego, California, January 17-20, 1996.
PMID- 10184654
TI - Heroin use among Miami's public school students, 1992: peers and the "drug
subculture" overwhelm parents, religion and schools.
AB - This analysis examines the use of heroin by 481 adolescents in Dade County,
Florida public schools during 1992. Statistically significant factors which tend
to increase the probability of heroin use by adolescents include: peer use of
heroin and students' involvement in school clubs. Not significantly related to
heroin use is their access to the drug, their ethnic background or race, and
their gender. Although not statistically significant, adolescents were more
likely to use heroin if they knew of the risks associated with heroin use. There
are no statistically significant variables which inhibit the rise of heroin by
Miami adolescents. When religion was an important part of their lives, they were
at lower risk for heroin use, but this was not significant. Also not
significantly related to heroin use are a number of other variables, including
family-related variables (whether adolescents live with their mothers, fathers,
or alone: and whether someone in the family has a problem with drugs or alcohol).
Similarly, early cigarette smoking and alcohol rise did not serve as gateways to
later heroin use. Academic performance, and extracurricular school activities
(athletics, music, and other activities) were all unrelated to the use of heroin
by adolescents, with the exception of involvement in school clubs which
substantially increased the risk of heroin use.
PMID- 10184656
TI - The Marshfield Clinic case: the sound of a broken record.
PMID- 10184657
TI - Beyond Baby M: international perspectives on gestational surrogacy and the demise
of the unitary biological mother.
PMID- 10184658
TI - Managed care meets EMTALA (Emergency Medical Treatment and Active Labor Act).
Clark v. Baton Rouge General Medical Center.
PMID- 10184659
TI - ERISA preemption clause bars application of any willing provider statute. CIGNA
Healthplan of Louisiana, Inc. v. Louisiana.
PMID- 10184660
TI - Exceeding expectations. Execs of 1-year-old Premier detail ambitious plans.
AB - At Premier's first anniversary shareholder meeting and governance conference last
week, top executives were quick to counter skeptics of the two-part merger that
formed the nation's largest hospital alliance a little more than a year ago. They
pointed to the merged alliance's raft of accomplishments during the past year and
promised more to come.
PMID- 10184661
TI - Meeting point. Association of Managed Healthcare Organizations, Orlando, Florida,
September 13-15, 1996.
PMID- 10184662
TI - The First Annual International Health Care Summit 1996, Mexico City. Meeting
report.
PMID- 10184663
TI - Limits on management discretion in personnel matters. Perkins v. Brigham &
Women's Hospital.
PMID- 10184664
TI - Court upholds summary judgment for hospital. Babcock v. St. Francis Medical
Center.
PMID- 10184665
TI - A telemedicine transaction model.
AB - The objective of this paper is to propose a telemedicine transaction model and a
set of terms to facilitate communication between telemedicine researchers,
program directors, and others. The model is described in terms of the sites,
personnel, and events involved. Examples of real-time, store-and-forward, and
physical referral transactions are depicted using the model. A hierarchy of
information classes for collaboration studies is developed based on their
relation to the frequency of data collection. Finally, a list of definitions is
given to specify the terminology used. The model is suitable for most
telemedicine systems, is useful in providing a common language for skilled
telemedicine participants, and can be used in comparative evaluation studies.
PMID- 10184666
TI - Summary of ICD-9-CM Coordination and Maintenance Committee meeting.
PMID- 10184667
TI - Nonreimbursable costs claimed under Medicare found to be criminal false
statement. United States v. Calhoon.
PMID- 10184668
TI - Start saving on materials before the hospital is built.
PMID- 10184669
TI - Sixth Circuit Court invalidates GME reaudit regulation. Toledo Hospital v.
Shalala.
PMID- 10184670
TI - Medicare/Medicaid restructuring. Challenges and opportunities of managed care.
AB - The restructuring of the Medicare and Medicaid programs poses significant
operational, legislative, and mission challenges for the Catholic health
ministry. This report highlights meetings held in Chicago and Philadelphia in
November and December 1996 to prepare healthcare leaders for the changes that are
coming. The meetings were two of seven held across the country last fall.
Cosponsored by the National Coalition on Catholic Health Care Ministry, the
Catholic Health Care Association (CHA), and Consolidated Catholic Health Care,
these regional conferences were part of New Covenant, a process to strengthen the
Catholic presence in healthcare through regional and national collaborative
strategies. The meetings blended operational and mission concerns. On the first
day, speakers reinforced mission as the ministry's foundation and market
advantage, and they defined opportunities and strategic responses to the
restructuring of the Medicare and Medicaid programs. The second day's sessions
moved into collaborative strategies for dealing with Medicare and Medicaid
changes. The day concluded with CHA's public policy proposals related to these
programs' restructuring.
PMID- 10184671
TI - Taming a runaway LTC board.
PMID- 10184673
TI - Data watch. Parlez-vous health speak?
PMID- 10184672
TI - Perspectives. Extramural GME makes gains one community at a time.
PMID- 10184674
TI - An Internet primer.
PMID- 10184675
TI - Hospital medical record copying practices provoke litigation. Clay v. Little
Company of Mary Hospital.
PMID- 10184676
TI - Confusing jury instructions lead to reversal. Ginsberg v. St. Michael's Hospital.
PMID- 10184677
TI - Insurers battle over copayment. SmileCare Dental Group v. Delta Dental Plan of
California, Inc.
PMID- 10184679
TI - Threat to cut off retiree's health insurance constitutes wrongful retaliation
under ERISA ... Stiltner v. Beretta Corp.
PMID- 10184678
TI - Proceedings of PRIDE Institute's symposium, July 16, 1996. Physician-assisted
suicide: potential impact of recent court decisions.
PMID- 10184680
TI - Disability law did not protect AIDS-infected M.D. who evaded employer's questions
... John Doe, M.D. v. Attorney General of the United States.
PMID- 10184681
TI - Third circuit opens gateway for lawsuits by Bjork-Shiley heart valve patients ...
Michael v. Shiley, Inc.
PMID- 10184682
TI - Red Cross has no governmental immunity to jury trials in AIDS lawsuits ...
Marcella v. Brandywine Hospital.
PMID- 10184683
TI - Sertraline. A pharmacoeconomic evaluation of its use in depression.
PMID- 10184684
TI - Review of disaster definitions.
AB - Researchers need accurate, explicit definitions of terms in order to discuss,
search for or identify the consequences of any particular phenomenon. The term
"disaster" is no exception. The many definitions used for definition of disaster
are outlined in general and by the discipline using them in this paper. Although
the definitions used still seem somewhat specific to the discipline, there is one
common element accepted by all: a disaster is seen to occur at a well-defined and
easily identified time. It is not feasible to formulate a universally acceptable
definition of disaster that will satisfy all practitioners, but common and agreed
upon definitions must be formulated in the various fields and areas concerned
with disasters, and where there exist recognizable, common sets of objectives.
PMID- 10184685
TI - The Academy of Managed Care Pharmacy, Orlando, Florida.
AB - The academy of Managed Care Pharmacy (AMCP) held its annual educational
conference between October 31 and November 3, 1996 in Orlando, Florida. The
meeting, which attracted about 1,500 delegates, offered some interesting plenary
and concurrent sessions, along with stimulating workshops and roundtables. Some
of the meeting content was dictated by current events, such as the Presidential
election, which took place only days after the conclusion of the conference.
PMID- 10184686
TI - Glossary. Managed care terms.
PMID- 10184687
TI - Classification systems: taking a broader look.
PMID- 10184688
TI - The American Society of Consultant Pharmacists, 27th annual meeting, November 13
16, 1996, Nashville, Tennessee.
AB - The 27th annual meeting of the American Society of Consultant Pharmacists (ASCP)
was held November 13-16, 1996 in Nashville, Tennessee. The conference boasted
numerous educational sessions and industry symposia. Clearly, the highlight of
this year's annual meeting for the more than 1,000 conferees was the release of
preliminary results of the Fleetwood Project, which seeks to quantify the value
of consultant pharmacists' services. In this issue, we describe these highly
anticipated data and a representation of other valuable educational sessions.
PMID- 10184689
TI - Sponsorship: with radical change comes opportunity.
PMID- 10184690
TI - Liability for damages for failure to observe no code order rejected. Anderson v.
St. Francis-St. George Hospital.
PMID- 10184691
TI - New Mexico courts deals with blood-alcohol test result. State v. Roper.
PMID- 10184692
TI - West Virginia court rules on covenant not to compete. Weaver v. Ritchie.
PMID- 10184693
TI - ERISA preemption. St. Francis Medical Center v. Blue Cross and Blue Shield of
Kansas, Inc.
AB - ERISA preempts hospital's state law action challenging insurer's rule banning
health plan participants from assigning their benefit claims to health care
providers who had not signed contracts with insurer.
PMID- 10184694
TI - ERISA preemption. Colleton Regional Hospital v. MRS Medical Review Systems Inc.
AB - ERISA preempts state law claims brought by hospitals against medical utilization
review firm including claims of tortious interference with contracts, defamation,
unfair trade practices, bad faith refusal to pay claims and improper claims
practices.
PMID- 10184695
TI - Talking in tongues.
PMID- 10184696
TI - Hospital repayment of Hill-Burton funds. United States of America v. NBC Bank
Rockdale.
PMID- 10184697
TI - Standardization and its call to health information managers.
PMID- 10184699
TI - Data dictionaries: an overview.
PMID- 10184698
TI - Toward standardization of health information.
AB - NCVHS has made recommendations to the DHHS to standardize 42 core health data
elements, a number of which relate to medical conditions and services. The
committee has asked the DHHS Data Council to actively promote, both within the
department and externally, standardization of data elements and definitions where
substantial consensus already exists. For those elements that have been
recognized as significant core data elements, but for which there is not
consensus on approach or definition, the NCVHS is recommending that the Data
Council support the formation of a public-private working group to conduct
further study and evaluation. This group, or a separate group, could also be the
focus for evaluating additions to the list of core data elements and for setting
up methods for testing and promulgating the final products. The coming 12-18
months will be exceedingly important for health data standardization efforts in
the US as the DHHS responds to both the NCVHS recommendations and the legislation
recently enacted by Congress.
PMID- 10184700
TI - Structured text--documentation meets technology.
PMID- 10184701
TI - Clinical terminologies and computer-based patient records.
PMID- 10184702
TI - Health purchasing. Waiting in the wings.
PMID- 10184703
TI - Anesthesia directors propose OR glossary.
PMID- 10184704
TI - Dispute over business deal raises broader issues of credentials, due process and
quality of care.
PMID- 10184705
TI - The National Health Lawyers Association. Annual Conference held December 11-13,
1996, in Atlanta, Georgia.
PMID- 10184706
TI - Turning around. New York City's HHC posts gains but still faces struggles.
PMID- 10184707
TI - HCQIA immunity denied by Tenth Circuit Court of Appeals. Brown v. Presbyterian
Healthcare Services.
PMID- 10184708
TI - Seventh Circuit rules physician may not sue under Title VII. Alexander v. Rush
North Shore Medical Center.
PMID- 10184709
TI - Was managed care a culprit? Paul v. Humana Medical Plan Inc.
PMID- 10184710
TI - Beer, trucks, cable TV, ATMs and hospitals.
PMID- 10184711
TI - Recovered memory: conflict, confusion and the need to think things through.
PMID- 10184712
TI - R v Human Fertilisation and Embryology Authority. Ex parte Blood. 17 October
1996.
PMID- 10184713
TI - Physician profiling can work in your favor.
PMID- 10184714
TI - HCV greatest bloodborne threat, expert says.
PMID- 10184715
TI - Healthcare reform. Foreign policies.
PMID- 10184717
TI - "Most Favored Nation" clauses under attack. United States v. Delta Dental of
Rhode Island.
PMID- 10184716
TI - Seller beware.
PMID- 10184718
TI - Marketing material can be perilous. Rowinsky v. Sperling.
PMID- 10184719
TI - A current compendium of cardiology technology.
PMID- 10184720
TI - Developing the effectiveness of an intersectoral food policy coalition through
formative evaluation.
AB - There is a difference between bringing parties together and making them work
effectively. We present a case study of an intersectoral food policy Committee,
part of a three-tiered coalition nested within local municipal government, which
sought to promote and nutrition in a rapidly growing metropolitan region by
tackling food supply issues in the first instance. This was new territory for all
players. After 12 months, the group felt it was floundering and requested an
evaluation. In-depth qualitative interviews with committee members (n = 21) and
quantitative assessment of Committee processes revealed insufficient mechanisms
for engaging new members, conflict between perceived roles for the group and a
notable lack of confidence in the group's capacity to achieve its goals, or
outcome efficacy. Feedback of the data and subsequent discussion led to a reform
of project structure, stronger mechanisms to realize its goals and better
incentive management, or ways to maximize the benefits and limit the costs for
the diverse parties involved. The impact was reflected in a 4 year time series
analysis of media releases, decision making and related municipal government
actions. The study illustrates how theory-informed formative evaluation can help
to improve health promotion practice.
PMID- 10184721
TI - Health Promotion: What's the Impact and What Works? Health promotion conference.
Hilton Head Island, South Carolina, March 3-8, 1997. Abstracts.
PMID- 10184722
TI - Virtual reality for autism communication and education, with lessons for medical
training simulators.
AB - This study is adapting Virtual Reality (VR) technologies to teach children with
autism new coping skills that may then be generalized in their everyday lives. It
helps to understand that children with autism are challenged by a sensory
overload and by aversions to a variety of auditory, visual, and tactile stimuli.
In addition, their ability to attenuate and/or ignore these stimuli differs from
that of the "typical" child. Therefore, our goals were to: 1. assess the
potential of each of the children (both with and without verbal skills) for
sustained interaction with task environments, 2. to identify which visual,
auditory, and kinetic VR components would be attractive to our test group, 3. to
identify each child's ability to attenuate and/or ignore a variety of
distractors, and 4. to build new "pivotal behaviors" [2] for learning. These
pivotal behaviors include: improvement of time-on-task, meaningful and consistent
interaction with the real world, and screening out extraneous environmental
stimuli. Our findings to date have been very encouraging, and we will continue to
investigate the role of VR as a tool for generalized learning and the
modification of pivotal behaviors. This ongoing study also provides technology
transfer of communications applications from government, universities and
businesses out into telemedicine and elementary schools.
PMID- 10184723
TI - Proceedings of the 1st European TELENURSE Conference. Athens, Greece.
PMID- 10184724
TI - Proceedings of the 1st European Congress on Health Telematics Education. Corfu,
Italy, 5-6 September 1996.
PMID- 10184725
TI - CHA amicus curiae brief on physician-assisted suicide. Catholic Health
Association.
AB - The Catholic Health Association of the United States submitted an amicus curiae
brief to the U.S. Supreme Court last October in support of petitioners Dennis C.
Vacco, attorney general of the state of New York (in the case Vacco v. Timothy E.
Quill, MD, et at.), and the state of Washington (in State of Washington, et al.
v. Harold Glucksberg, MD, et al.). The brief was filed as the Court agreed to
hear arguments on the issue of whether terminally ill people have a
constitutionally protected right to physician-assisted suicide. In January 1997
the petitioners went before the Court to argue appeals to federal appellate
rulings that struck down New York and Washington laws making physician-assisted
suicide a crime. The Court is expected to rule in late June.
PMID- 10184726
TI - Illinois appellate court upholds prohibition on hospital employment of
physicians. Holden v. Rockford Memorial Hospital.
PMID- 10184727
TI - Is time running out on Medicare? Rep. Deal to GHA Board: 'Racheting down money to
providers is not a structural change'.
PMID- 10184728
TI - Getting beyond industrial logic: renewing our faith in the value of health.
PMID- 10184729
TI - Risk management investigation reports discoverable. Klonoski v. Mahlab.
PMID- 10184730
TI - Hospital has nondelegable duty to ensure quality of emergency care. Sampson v.
Baptist Memorial Hospital System.
PMID- 10184732
TI - Texas recognizes cause of action for intentional spoilation of evidence. Ortega
v. Trevino.
PMID- 10184731
TI - Employer may discipline on basis of current substance abuse. Shafer v. Preston
Memorial Hospital.
PMID- 10184733
TI - Termination for sleeping on the job not wrongful. Brohm v. JH Properties, Inc.
PMID- 10184734
TI - The challenge of health care branding.
PMID- 10184735
TI - Cost-benefit analysis identifies best practices.
AB - Managers who want to prove the value of procedures or equipment choices will do
well to include a detailed cost-benefit analysis in their best practices
summaries. That's the approach same-day surgery managers took to prove certain
laparoscopic procedures were cost-effective as well as best practice. Patients
with laparoscopic appendectomy spent less time in the hospital, required fewer
doses of Demerol postoperatively, experienced less blood loss, and returned to
work more quickly, according to a literature search by Vangie Paschall, RN, CNOR,
laser endoscopic coordinator at Promina Gwinnett Health System in Lawrenceville,
GA. Although laparoscopic appendectomy involves a small additional cost, it
attracts payers who want good quality outcomes for patients.
PMID- 10184736
TI - Immunity for state employed physicians left uncertain after Keenan decision.
PMID- 10184737
TI - Invited papers emphasize management skills.
PMID- 10184738
TI - Group purchasing--an international future? Health Industry Group Purchasing
Association Expo Conference, October 9-11, 1996, Orlando, Florida, USA.
AB - As Providers and suppliers in the U.S. health care market place have adopted a
mindset more attuned to today's economic realities, they've made cost cutting a
top priority-and to help them achieve that, they have turned to GPOs and the
prospects they offer for control of supply costs through bulk buying. Will the
purchasing world cross international boundaries and get even smaller? What
benefits can be expected from group purchasing organisations developing an
international network? Can the International Hospital Federation play a role?
PMID- 10184740
TI - New HFMA initiatives. Employment assistance, expanded alliances among plans.
PMID- 10184739
TI - Bone research in biomechanics. Proceedings of the 10th Conference of the European
Society of Biomechanics. Leuven, Belgium, 28-31 August 1996.
PMID- 10184741
TI - Appropriate and necessary healthcare: new language for a new era.
AB - Conceptual and language changes are necessary to accompany the paradigm shift
from fee-for-service medicine to managed care. Medical necessity is an inadequate
and ambiguous term defined differently by providers, payers, patients, and
legislators. The attempt by legislators in Minnesota to develop a universal
standard benefits set for healthcare services strikingly underscores the need to
define relevant terminology to accompany the transition to managed care. We
suggest the term appropriate and necessary healthcare as a state-of-the-art term
for the new era of managed care.
PMID- 10184742
TI - Encountering the American health information management profession.
PMID- 10184743
TI - National leaders meet on public access defibrillation.
PMID- 10184744
TI - Cool stuff. JEMS' techno-wizard cruises EMS today for equipment innovations.
PMID- 10184745
TI - Cardiac troponin T in the risk assessment of acute coronary syndromes.
PMID- 10184746
TI - A three-year follow-up survey of demographic changes in a Ugandan town on the
trans-African highway with high HIV-1 seroprevalence.
AB - A 1991 serosurvey in a Ugandan trading town on the trans-African highway reported
a 40 per cent HIV-1 prevalence in adults. Three years later in a repeat survey of
the 531 adults resident in 1991, 279 (53%) were still present, 196 (37%) had left
and 56 (11%) had died. There were 138 new residents and 46 children had become
adults, making a total of 463 adults in 1994, 13 per cent less than 1991. Most
immigrants (91%) came from the surrounding rural district whereas 38 per cent of
emigrants went to an urban area. A significant inverse association between wealth
and seropositivity was found for women but not men. Of the original residents 157
were known to be HIV-1 positive in 1991; 31 (20%) had died compared to 10 (4%) of
the 232 known to be seronegative, representing an HIV-1 attributable mortality
fraction of 60 per cent.
PMID- 10184747
TI - Adolescent sexual networking and HIV transmission in rural Uganda.
AB - Information on 861 adolescents shows that in 1991 36 per cent reported having
been sexually active in the previous 12 months, but only 6.2 per cent had ever
used a condom (11% males, 2.4% females). The HIV infection rate was 5.9 per cent
overall, 0.8 per cent in males and 9.9 per cent in females. The proportion
sexually active and the rate of HIV infection rise with age. The annual incidence
of HIV infection was 2.0 per 100 person-years of follow-up among all adolescents,
0.8 in males and 3.0 in females. The annual mortality rate among HIV-negative
adolescents was 0.37 per cent versus 3.92 per cent among the HIV-positive
adolescents, a rate ratio of 10.6. Sexual network data were collected on 389
adolescents aged 15-19 years of whom 55 per cent were sexually active. The median
age of first sexual intercourse was 15 years in either sex. The 214 adolescents
reported 339 sexual relationships of which 38.5 per cent were with spouses, 36
per cent with boy or girl friends and 21 per cent with 'friends'. There were 52
concurrent sexual relationships reported by 35 adolescents. Males report higher
rates of concurrent sexual relationships than females. The sexual partners of
boys were mainly younger students and housemaids while the girls' partners were
mainly older traders and salaried workers. Adolescents in this community report
high rates of sexual activity and have complex sexual networks. They probably are
important in the dynamics of HIV infection.
PMID- 10184748
TI - Clinical considerations in GERD (gastroesophageal reflux disease) therapy: focus
on cisapride.
AB - Heartburn, the major symptom of gastrointestinal reflux disease (GERD), is a
common condition that is usually self-treated with over-the-counter products. For
patients with severe or recurrent symptoms of GERD, pharmacologic therapy
includes acid suppression with H2-receptor antagonists and proton pump
inhibitors, and, alternatively, the use of prokinetic agents. While all of these
are efficacious, given its high efficacy in nonerosive and mild-to-moderate
erosive esophagitis, the prokinetic agent cisapride deserves significant
consideration in this patient population.
PMID- 10184749
TI - Physician-patient arbitration agreements ruled enforceable. Buraczynski v.
Eyring.
PMID- 10184750
TI - Medical necessity: a term of many meanings. Bellaire General Hospital v. Blue
Cross Shield of Michigan.
PMID- 10184751
TI - State court ruling protecting QA records is important for all SNFs. State of
Missouri, ex. rel., Boone Retirement Center Inc. v. Hamilton.
PMID- 10184752
TI - Good data collection strategies are key to a successful outcomes system.
PMID- 10184753
TI - Symposium explores information management in the OR.
PMID- 10184754
TI - Potential for liability under the Consent to Treatment Act.
PMID- 10184755
TI - California decision bars dismissal of physician from provider network without
cause. Potvin v. Metropolitan Life Insurance Company.
PMID- 10184756
TI - Complaint alleging breach of ERISA fiduciary obligation upheld. Shea v. Esensten.
PMID- 10184757
TI - Two courts wrestle with patients' records issues.
PMID- 10184758
TI - Five steps subacute providers can take to prepare for an uncertain future.
PMID- 10184759
TI - Court invalidates HCFA's orthotic management ruling.
PMID- 10184760
TI - Interfacing managed care and long-term care: understanding the issues.
AB - Both marketplace forces and legislative initiatives are forcing the traditional
fee-for-service long-term health care sector into the managed care arena. To
identify and address the issues surrounding quality and cost-effective
pharmaceutical use at the interface between managed care and long-term care, the
Philadelphia College of Pharmacy and Science convened a day-long conference
between managed care and long-term care medical and pharmacy directors. This
paper outlines the discussion and recommendations in respect to these issues.
PMID- 10184761
TI - New kid on the block--National Association of EMS Educators (NAEMSE).
PMID- 10184763
TI - Deselection ruling hits managed care. Louis E. Potvin v. Metropolitan Life
Insurance Company.
PMID- 10184762
TI - TQM in health care: mistaken identity?
AB - Total Quality Management is a powerful tool in health care today. The definition
of quality improvement in the medical literature focuses on improving patient
outcomes. However, most quality initiatives in the health care field focus on
improving productivity, cost-effectiveness, market share, employee morale, and
efficiencies of processes. This disparity between the medical definition of
quality and the actual application of quality improvement may have the effect of
alienating many physicians, the very people who must be involved. The semantics
are important to address in a TQM initiative.
PMID- 10184764
TI - Beyond incompatibility: integrating process for optimal performance.
AB - Organizations are bringing disparate groups together to cut costs and integrate
services. Ironically, they are finding the very people they look to for success
are those who were used to working independently. At a breakout session of the
Congress of Integrated Delivery Systems held in Dallas in March, 1997,
participants were asked to share some of their real-world experiences as they
worked toward integration. Mission statements tend to be at the head of the list
for most organizations as they strive to integrate. Not all the participants
agreed on their value, however. The success of reengineering depends on many
factors. Is the facility fully behind the initiative? Is the team cohesive and
focused? One participant pointed out that leadership was a problem: the staff was
not empowered and in the end, the organization was leaderless--someone has to
take control, this manager stated. Some groups have found that starting with a
clean slate is helpful, particularly if the whole operation is flawed. Another
manager felt that wiping the slate clean is not always the answer. Some
industries have always looked at business along product lines and now healthcare
is attempting to do the same. Will it work? One participant answered that this
view has helped her organization see who their patients are. Another insists it
has facilitated teamwork between disciplines. All would agree that communication
is critical. Most agree that e-mail is a good tool and to some, it is invaluable.
Slowly but surely, each organization will have to learn how to integrate its own
processes and services.
PMID- 10184765
TI - Issues of medical necessity: a medical director's guide to good faith
adjudication.
AB - The term medical necessity is difficult to define, a problem for insurers who
need to clearly describe what is and is not covered in their contracts with
subscribers. An unclear, vague definition of medical necessity leaves insurers
vulnerable to litigation by subscribers denied care deemed medically unnecessary.
To avoid lawsuits, insurers must make every effort to educate their subscribers
about their medical coverage, going beyond merely providing a lengthy subscriber
handbook. In decisions on medical necessity, medical directors at insurance
companies play a key role. They can bolster the insurer's position in denial-of
care cases in numerous ways, including keeping meticulous records, eliminating
unreasonable financial incentives, maintaining a claims denial database, and
consulting with other insurers to achieve a consensus on medical necessity.
PMID- 10184766
TI - Withholding life-sustaining treatment: the case of Miss D.
PMID- 10184767
TI - Court-authorised caesareans: new guidance.
PMID- 10184769
TI - Home care, Part II--Generating referrals for social work intervention.
PMID- 10184768
TI - Maternity care.
PMID- 10184770
TI - Suggested activities for caregivers of patients with cardiovascular and
cerebrovascular disease.
AB - The cardiology industry has placed a strong emphasis on the need of all
individuals participating in the care of patients with cardiovascular and
cerebrovascular disorders to become proactive in their involvement perpetuating
the continued works of the medical industry. This article discusses suggested
activities.
PMID- 10184771
TI - Liability does not attach for wrongful resuscitation. Anderson v. St. Francis-St.
George Hospital.
PMID- 10184772
TI - EMTALA not applicable to DNR orders after admission. Bryan v. Rectors and
Visitors of the University of Virginia.
PMID- 10184773
TI - Failure to follow specific language in consent may be basis for liability.
Legenbuhl v. Douling.
PMID- 10184774
TI - Workers' compensation is sole remedy for volunteer's work-related injury. Alander
v. Vaca Valley Hospital.
PMID- 10184775
TI - Providers need not disclose HIV status to third parties. Lemon v. Stewart.
PMID- 10184776
TI - Professional liability. Jurisdictions split on discoverability of risk management
information.
PMID- 10184777
TI - Hospital may be liable for failure to accommodate patient's deafness. Negron v.
Snoqualmie Valley Hospital.
PMID- 10184778
TI - Post-traumatic stress disorder may be compensable. Means v. Baltimore County,
Maryland.
PMID- 10184779
TI - The Consent to Treatment Act and an adolescent with anorexia nervosa.
PMID- 10184780
TI - Proceedings of the 1st biannual meeting of the International Research Society of
Spinal Deformities. Stockholm, Sweden, June 16-19, 1996.
PMID- 10184781
TI - A common strategic language for clinicians and senior managers.
AB - Effective strategic analysis of existing and potential services requires a
framework which is relevant and understandable to both clinicians and senior
managers. Our work with NHS trusts has developed a framework based on analysis of
services into four principal service streams--emergency general hospital, non
emergency general hospital, specialist general hospital and tertiary. Relating
service streams to clinical specialties provides a matrix which can provide a
basis for an initial analysis of the current and prospective clinical services
portfolio, allowing drilling down into the detail and back up to the overall
picture. Portfolio effectiveness is assessed by considering overall viability
consisting of three interrelated elements--clinical, market and financial
viability. The interrelationship of service streams, clinical specialties and
viability allows the trust board and key clinicians to share insights into the
current and potential systemic linkages between these three elements and to
develop a vision of future strategic direction.
PMID- 10184782
TI - Anesthesiologists tangle with hard-nosed insurer. Ambroze v. Aetna Health Plans
of New York, Inc.
PMID- 10184783
TI - Exception to physician-patient privilege ruled inapplicable. Chung v. Legacy
Corporation.
PMID- 10184784
TI - An equality approach to wrongful birth statutes.
PMID- 10184785
TI - Methodology for assessment of medical IT-based systems in an organisational
context.
PMID- 10184786
TI - Post-decision diagnosis: medical device preemption alive and mostly well after
Medtronic, Inc. v. Lohr.
AB - In Medtronic, Inc. v. Lohr, the United States Supreme Court, in a five-to-four
split, held that the Medical Device Amendments of 1976 did not preempt state tort
claims against a pacemaker manufacturer. A careful reading of the factually
specific holding of this case suggests that manufacturers of medical devices
distributed pursuant to premarket approval requirements and investigational
device exemption can still successfully raise preemption as a defense to state
common law tort claims.
PMID- 10184787
TI - The Ps and Qs about acronyms.
PMID- 10184788
TI - Fidelity to mission: our strategic strength. 82nd Catholic Health Assembly, June
8-11, 1997.
PMID- 10184789
TI - Lab may be sued in state where specimen originates.
PMID- 10184790
TI - Court of appeals defines HCFA 1500 Form as a "claim" under the False Claims Act.
United States v. Krizek.
PMID- 10184791
TI - A rapid bedside troponin T assay to speed triage.
PMID- 10184792
TI - Seminar highlights importance of legal issues facing telemedicine.
PMID- 10184793
TI - Social work's role in population management: Part I.
PMID- 10184794
TI - Fair procedure? Potvin v. Metropolitan Life Insurance Company.
PMID- 10184795
TI - The home care market: experts call for better marketing, outcomes data.
PMID- 10184796
TI - Home care and the integrated delivery system: disease management is the link.
PMID- 10184797
TI - Punitive damages awarded in hospital employment case.
PMID- 10184798
TI - What's happening to private practice? Panel discussion.
PMID- 10184799
TI - A workshop and symposium on haemopoietic stem cells. 16th April 1996.
PMID- 10184800
TI - How safe are computerized patient records?
PMID- 10184801
TI - Nine years of computerized patient records in a small family practice.
PMID- 10184802
TI - Strategies for chronic disease management.
PMID- 10184803
TI - IHF Congress highlights. A sampling of the offerings at this year's meeting in
Melbourne, Australia.
PMID- 10184804
TI - Providers can decrease costs, improve care by learning from errors, but only if
they stop playing the "blame game".
PMID- 10184805
TI - Part I--IEPS (Institute for the Study of Health Policies) reports. The proper
function of teaching hospitals within health systems.
AB - The main points of the discussions from the international seminar organised by
the World Health Organisation and the Institute for the Study of Health Policies
(IEPS) were published in French by Flammarion Medecine-Sciences in the Collection
entitled "The IEPS Reports" and in English by the WHO under the title "The Proper
Function of Teaching Hospitals within Health Systems" (1995).
PMID- 10184806
TI - Arizona suit lights fire; HCFA plans revision of grievance and appeals. Grijalva
v. Shalala.
PMID- 10184807
TI - Matters of the heart.
PMID- 10184808
TI - Court upholds invalidation of improperly obtained search warrants.
PMID- 10184809
TI - Virtual reality for the treatment of autism.
AB - Autism is a mental disorder which has received attention in several unrelated
studies using virtual reality. One of the first attempts was to diagnose children
with special needs at Tokyo University using a sandbox playing technique.
Although operating the computer controls proved to be too difficult for the
individuals with autism in the Tokyo study, research at the University of
Nottingham, UK, is successful in using VR as a learning aid for children with a
variety of disorders including autism. Both centers used flat screen computer
systems with virtual scenes. Another study which concentrated on using VR as a
learning aid with an immersive headset system is described in detail in this
chapter. Perhaps because of the seriousness of the disorder and the lack of
effective treatments, autism has received more study than attention deficit
disorders, although both would appear to benefit from many of the same technology
features.
PMID- 10184810
TI - Development of a virtual sand box: an application of virtual environment for
psychological treatment.
AB - The sand play technique has often been used in psychological treatments or in the
diagnosis of autism patients. In this paper, the prototype application called
"virtual sand box" is developed as a virtual environment to support this
technique. Experimental results show the advantages of applying virtual reality
technology to clinical medicine; particularly with respect to the diagnosis of
people with psychological and psychiatrical difficulties such as autism and
neurosis. The actual system has been implemented by using a graphics workstation,
a wide-view field display, and 3D input devices.
PMID- 10184811
TI - A compositional approach to nursing terminology.
AB - The development of standardised vocabularies within nursing has been an important
research activity for a number of years. Current representations generally take
the form of taxonomic vocabularies. These are seen as important as they provide a
structure for retrieving and analysing data from automated systems. However,
there is increasing evidence to show that traditional taxonomic vocabularies are
unsuitable for capturing detailed clinical data. This paper describes how GRAIL
(GALEN Representation and Integration Language) is being used within the
TELENURSE project to develop a representation of nursing terminology which is
sufficiently expressive for documenting detailed clinical data while retaining
the benefits of traditional taxonomic vocabularies.
PMID- 10184812
TI - Strategies and tools for creating a common nursing terminology within a large
health maintenance organization.
AB - A common nursing terminology is essential for outcomes research, data
comparability and clinical documentation in an electronic health record. Kaiser
Permanente has recognized the need to develop a common nursing and medical
terminology across the program. The Interregional Nursing Nomenclature Committee
has developed a model for developing a common nursing terminology integrated with
other healthcare terminologies.
PMID- 10184813
TI - The Danish National Health Classification system--Nursing Interventions
Classification--a part of a common Danish Health Care Classification.
AB - The Danish Nursing Intervention Classification is the first national nursing
intervention classification. Because of the official status of the project it is
to be a national standard. It will thus be possible for the system to be in
general use nation-wide, which is a necessary condition for an efficient
communication in the health care sector in Denmark.
PMID- 10184814
TI - Nursing Information and Data Set Evaluation Center.
AB - The American Nurses Association (ANA) has established the Nursing Information and
Data Set Evaluation Center (NIDSEC). The purpose of this Center is to develop and
disseminate standards pertaining to information systems that support the
documentation of nursing practice, and to evaluate voluntarily submitted
information systems against these standards. The target audience for these
standards includes both consumers and vendors of clinical information systems.
The need for an evaluation center arises out of a long history of calls for
standards pertaining to nursing data and to information systems. These calls have
come from the Secretary of Health and Human Services Commission on Nursing, the
National Commission on Nursing Implementation Project (NICNIP). Standards will be
developed to evaluate the completeness, accuracy and appropriateness of four
dimensions of nursing data sets and the systems that contain them: 1)
Nomenclature; 2) Clinical Content; 3) Clinical Data Repository; and 4) General
System Characteristics.
PMID- 10184815
TI - European standardization in healthcare informatics and the need for increased
involvement of healthcare professionals.
AB - This paper gives the background and an introduction to the results and present
activities of CEN/TC 251 (European Standardization Committee, Technical Committee
on Health Care Informatics). The importance of the involvement of healthcare
professionals, e.g. nurses, in the standardization development process is
stressed. The paper emphasises the need for increased awareness of the
standardization efforts in order to accomplish a higher degree of commitment in
healthcare professionals.
PMID- 10184816
TI - A national framework for district nurses' uniform documentation patient records.
PMID- 10184817
TI - The VIPS model--implementation and validity in different areas of nursing care.
AB - The development of common concepts and terms for nursing practice is crucial for
the effective use of nursing-information systems. In Sweden, the VIPS model has
been developed to support the systematic and common documentation of nursing care
in patient records. The model has been widely used in different areas of nursing
practice. This literature review was conducted as a part of a larger project to
study the validity and reliability of the VIPS model, as well as its
dissemination into the Swedish health-care system. The findings showed in general
good reliability and content validity for the keywords in the VIPS model. The
implications for the further development of the model are discussed.
PMID- 10184818
TI - Brave new medicine. Wondrous technology could bring back the house call.
PMID- 10184819
TI - Unenforceable today, enforceable tomorrow--Illinois Supreme Court reverses Berlin
decision. Richard B. Berlin, Jr., M.D. v. Sara Bush Lincoln Health Center.
PMID- 10184820
TI - A new perspective on hospital financial ratio analysis.
AB - Using audit financial data in a study of 2,189 not-for-profit hospitals for the
period 1989-1992, six financial characteristics of performance were defined.
These characteristics are profitability factor, fixed-asset efficiency, capital
structure, fixed-asset age, working capital efficiency, and liquidity. The
statistical output also shows the specific sets of financial ratios that can be
used to measure the six characteristics of hospital performance. The results of
this study can be beneficial to healthcare financial managers, hospital boards,
policy groups, and other relevant entities because it affords them a clear
understanding of an institution's financial performance.
PMID- 10184821
TI - Shades of the rainbow. EMS providers come in all color--so do patients. How the
differences can affect treatment.
PMID- 10184822
TI - Court decisions direct renewed attention to discovery issues. Klonski v. Mahlab;
State ex rel. United Hosp. Ctr. v. Bedell.
PMID- 10184823
TI - Summary judgment for defendants in challenge to hospital department closure.
Healow v. Anesthesia Partners, Inc.
PMID- 10184824
TI - Critic's corner ... consent forms in hospital settings.
PMID- 10184825
TI - Transition and long-term strategies key to survival under prospective payment.
PMID- 10184826
TI - Make your medical management committee a forum for action.
PMID- 10184827
TI - The struggle to define what 'Intranet-enabled' really means.
PMID- 10184828
TI - Evidence-based tools help move patients through the continuum quickly,
efficiently and safely.
PMID- 10184829
TI - Stokes shares food facility design and management tips with ASHFSA audience.
PMID- 10184830
TI - Managing with managed care. Meeting patients' foodservice needs in a system in
transition.
PMID- 10184831
TI - Hospital losses mean PhyCor's gain, exec says.
PMID- 10184832
TI - Prudent by whose standards? Eagle Healthcare v. Mutual of Omaha.
PMID- 10184833
TI - A question of health. The lottery of cancer care.
PMID- 10184834
TI - Hepatitis C prevalence and the significance of liver enzyme elevations in the
insurance population.
AB - BACKGROUND: Liver enzyme elevation(s) are a common finding in the insurance
applicant population. Hepatitis C infection results in histological and
functional changes in the liver with both short and long term changes in serum
liver enzyme levels. The prevalence of antibodies to HCV in the general
population is estimated to be 4%. This paper reports on the prevalence of
antibodies to HCV in the insurance applicant population and their relationship to
the liver enzyme(s). RESULTS: Antibodies to HCV are present in 1.8% of a random
sampling of insurance applicants. Alanine aminotransferase (ALT) elevations occur
in 95.4% of all samples positive for antibodies to HCV. More than half of
positive samples (56.7%) have ALT elevations of less than two time the upper
range of normal. Antibody prevalence is lowest in samples with single enzyme
elevation, 4.2%. In comparison, the prevalence is 16.4% in samples with all three
enzymes, ALT, AST, and GGT, elevated. For maximal specificity two immunoassays,
configured with different HCV antigens, should be performed sequentially on all
positive applicant samples. CONCLUSION: HCV is the most prevalent, chronic viral
infection in the insurance population. HCV prevalence is 40 times HIV prevalence.
In an evaluation of enzyme reflex markers ALT was positive for antibodies to HCV
8.6% of the time while identifying 95.4% of HCV antibody positive applicants.
PMID- 10184836
TI - The Atlantic Rim Telemedicine Summit. Boston, Massachusetts, USA, May 1997.
AB - The Transatlantic Telemedicine Summit was convened to facilitate the
international exchange of ideas and experiences regarding anticipated obstacles
to the deployment of telemedicine in and among Atlantic Rim countries. Presented
here is a review and summary of the Summit, as well as the principal
recommendations derived from the proceedings. These recommendations provide a
basis for the further development of cooperative efforts in international
telemedicine.
PMID- 10184837
TI - New Technologies in Hospital Information Systems. Conference proceedings. Ulm,
Germany, 20-23 September 1997.
PMID- 10184835
TI - Clinical and economic comparison of sertraline and fluoxetine in the treatment of
depression. A 6-month double-blind study in a primary-care setting in France.
AB - In a double-blind study in a primary-care setting in France, outpatients
fulfilling DSM IV criteria for a major depressive episode were randomised to
receive sertraline (50 to 150 mg/day; n = 122) or fluoxetine (20 to 60 mg/day; n
= 120). Assessments, including clinical evaluation [Montgomery-Asberg Depression
Rating Scale (MADRS), Clinical Global Impressions (CGI)] and quality of life
[Functional Status Questionnaire (FSQ)], were made at study entry and after 4 and
6 months of treatment. Use of medical services, absences from work and
productivity losses were recorded for calculation of direct and indirect costs
from both the overall societal perspective and in terms of sickness insurance. In
total, 231 patients (116 receiving sertraline, 115 receiving fluoxetine) were
included in an intention-to-treat analysis assessed up to the last visit.
Statistically significant clinical and quality-of-life improvements from baseline
were observed in both treatment groups, with no between-group differences.
Utilisation of medical resources was higher in fluoxetine-treated patients, with
significantly more consultations with specialists. The 2 treatment groups were
similar in terms of number of hospitalisations and duration of stay, whether
related to depression or not. There were no significant differences between
groups for work or productivity losses. Cost comparisons favoured sertraline
treatment from both the societal (FF7780 vs FF8706) and sickness insurance
(FF2936 vs FF3224) viewpoints, with cost differentials of FF926 and FF288,
respectively. From the societal perspective, the total cost per patient over the
6-month course of the trial, irrespective of the study treatment given, was
FF8241, and the corresponding sickness insurance cost was FF3079. At the time of
the study, FF1 = $US0.1993.
PMID- 10184838
TI - Biocompatibility: the latest developments.
AB - The standards for biological evaluation of medical devices are currently being
evaluated. This article presents the rationale behind the current ISO 10993
series and discusses the work in progress to revise elements of the standards and
to incorporate new areas. Particular issues being addressed include a new
definition of biocompatibility, and quality of health, which will include product
risk assessment and surveillance in the market place.
PMID- 10184839
TI - Ethical issue arises from "run-of-the-mill" professional discipline proceeding.
Nevada State Board of Nursing v. Merkley.
PMID- 10184841
TI - Nursing facilities should look to the EverCare model to better position
themselves for capitation.
PMID- 10184840
TI - Medtronic v. Lohr: state lawsuits may proceed against medical device
manufacturers.
PMID- 10184842
TI - Pa. tax law targeted. Suit: property tax shield unconstitutional.
PMID- 10184843
TI - Your duty to warn non-patients.
PMID- 10184844
TI - Risk management information may be discoverable. State ex rel. United Hospital
Center v. Bedell.
PMID- 10184845
TI - Records of quality assurance committee protected from discovery. State ex rel.
Boone Retirement Center v. Hamilton.
PMID- 10184846
TI - ED agreement creates potential liability for staffing corporation. McClendon v.
Crowder.
PMID- 10184847
TI - Hospital strictly liable for providing defective product to patient. Mulligan v.
Truman Medical Center.
PMID- 10184848
TI - Facility may be liable for harassment by resident. Crist v. Focus Homes, Inc.
PMID- 10184849
TI - Marking progress toward service integration: learning to use evaluation to
overcome barriers.
AB - While federal statutes defining categorical programs and funding streams are most
often cited as barriers to service integration efforts, there is evidence that
service integration efforts are also being stymied by factors at the state and
local levels as well. This case study examines five types of barriers to service
integration that have been evident in Georgia's Family Connection and describes
how an evaluation instrument and process was developed to assess progress toward
service integration at the local level. The findings of a pilot study of the use
of this instrument suggest that it can help to: (a) define starting points for
service integration efforts; (b) identify specific service integration activities
that are feasible in the context of a unique community; (c) specify the time
needed to be allocated to service integration efforts; (d) identify the local
costs and benefits of engaging in service integration; and (e) provide
specifications for conducting a self-assessment of progress at the local level
toward service integration goals.
PMID- 10184850
TI - "Physician, get thyself mad".
PMID- 10184851
TI - Diabetes care: an opportunity for collaboration.
PMID- 10184852
TI - Hospital losses mean PhyCor's gain, exec says.
PMID- 10184854
TI - Sunny forecast. Meditrust's Gosman among boosters of rapidly growing assisted
living industry.
PMID- 10184853
TI - Meeting JCAHO's tough age-specific standard.
PMID- 10184855
TI - Marketplace. The pioneers' recipes for PSO success in Medicare market.
PMID- 10184856
TI - The devil is in the details: managed care contracting do's and don'ts.
PMID- 10184857
TI - No magic bullet. World no longer looks to U.S. for secret formula to solve
healthcare problems.
PMID- 10184858
TI - Disease management: wave of the future.
PMID- 10184859
TI - A guide to health data terms.
PMID- 10184860
TI - Release of reports of child abuse is subject to qualified privilege. Bol v. Cole.
PMID- 10184861
TI - Court invalidates HCFA construction of outlier statute. County of Los Angeles v.
Shalala.
PMID- 10184862
TI - AHA sets agenda. Association outlines priorities, celebrates centennial.
PMID- 10184864
TI - King instated as AHA board chair.
PMID- 10184863
TI - AHA's theme: scale back fraud probes.
PMID- 10184865
TI - Tough on trustees. AHA approves 'desirable criteria' for joining board.
PMID- 10184866
TI - JCAHO board to discuss self-reporting.
PMID- 10184867
TI - A cost-effectiveness study of changing medical practice in early pregnancy.
AB - Until recent years women with symptoms consistent with miscarriage either
referred themselves or were referred by their doctors to the local Accident and
Emergency (A&E) department. This generally resulted in admission to a
gynaecological ward and delayed treatment. Examines the costs and benefits of an
Early Pregnancy Assessment Clinic (EPAC), at a teaching hospital in North East
England, to deal with the complications in the first trimester. The data show
clear benefits together with cost savings. There is an unambiguous policy
recommendation to implement the proposed clinic. Examines the delivery of service
provision and the impact on referral patterns to the A&E department. Raises the
issue of care provision at the margin. Finally, shows the results of an
evaluative survey of the clinic from returns of a questionnaire sent to and
completed by local general practitioners.
PMID- 10184868
TI - A matter of distinction.
AB - Two years after moving into a specialist unit, clients with autism displayed a
significant reduction in antisocial behaviours. Services for people with autism
should be distinct from those for people with learning disabilities. The
accreditation process of the National Autistic Society proved a vital element in
developing the new service.
PMID- 10184869
TI - Report from the NCEPOD briefing meeting.
PMID- 10184870
TI - Employee handbook held to create a contract. Doyle v. Holy Cross Hospital.
PMID- 10184871
TI - Psychologist protected by qualified privilege. Bol v. Cole.
PMID- 10184872
TI - Glossary. Internet definitions.
PMID- 10184873
TI - Taping meetings in the hospital. Hernandez v. McDonald's Corporation.
PMID- 10184874
TI - New Jersey court rules against terminated medical resident. Hernandez v. Overlook
Hospital.
PMID- 10184875
TI - Cigarette-smoking 'dementia' patient dies in fire: is hospital to blame?
PMID- 10184876
TI - A concept-based medication vocabulary: an essential requirement for pharmacy
decision support.
AB - The impact of adverse drug events (ADEs) on the cost and quality of health care
today is indisputable. A significant portion of these events can be detected and
prevented with computerized pharmacy decision support systems. Challenges to the
successful implementation of decision support systems include availability and
quality of patient data and the accessibility of drug information that can be
integrated programmatically on a patient-specific basis. An additional related
challenge is establishing the vocabulary (i.e., codes, terms, and meanings) to be
used for the representation, exchange, and automation of drug information and
clinical functions. A central argument of this article is that a concept-based
medication vocabulary needs to be created in order to facilitate the development
of pharmacy decision support. We address the medication vocabulary challenge by
defining a specific concept-based model of drugs as the basis for a standardized
medication terminology.
PMID- 10184877
TI - Health care in the courts. The result of the fatal accident inquiry at Kilmarnock
Sheriff Court into the death of Rebecca Cassidy. 26 June 1997.
PMID- 10184878
TI - U.S. exports managed care successes.
PMID- 10184879
TI - Secondary prevention in coronary heart disease.
PMID- 10184880
TI - "The horse on the dining room table". Institutional arrangements for perinatal
death.
PMID- 10184881
TI - Battling the nursing home stigma. Think nationally, act locally for good public
relations.
PMID- 10184882
TI - Finding the on ramp: accessing the information superhighway.
PMID- 10184883
TI - Current conceptualizations of mental health and mental health promotion.
AB - Health promotion is generally agreed to be underpinned by a set of principles
which distinguish it from other disciplines and professions. This paper takes
these principles as the starting point for a review of the literature of mental
health promotion. The aim is to clarify the ways in which mental health and
mental health promotion are currently conceptualized, in order to identify areas
where health promotion can make a unique contribution to complement that of other
interest groups. In the first section, it is suggested that current definitions
of mental health are inadequate for health promotion practice in that they either
equate health with the absence of illness or present a culturally skewed,
individualized and 'expert'-led version of what it means to be mentally healthy.
The second section then traces the implications of these definitions as they
emerge from the literature relating to mental health promotion practice. The
paper concludes with a discussion of some ways in which health promotion
specialists might begin to develop a mental health promotion agenda which is more
consistent with health promotion principles.
PMID- 10184884
TI - Integrated delivery and financing systems: some current challenges.
PMID- 10184885
TI - Outcomes research is the fifth discipline of the fifth generation of managed
care: utility of a single troponin-T.
AB - OBJECTIVE: The fifth generation of managed care is disease management. Diseases
have measurable risk in providing laboratory and medical services. The link
between managing services and managing risk can be aided by leveraging the
laboratory. We wish to remodel laboratory services to fit the needs of the use,
thereby using the laboratory for competitive advantage by redesigning a desired
output using a formal structured process. Outcomes research is the systems
framework for the remodeling process through the link of laboratory output to
clinical and financial outcomes. A process redesign model connects the use of
laboratory tests to improved medical services by leveraging resources to achieve
measurable improvement over current results. This view of outcomes research seeks
both competitive advantage and measurable improvements in quality. METHODOLOGY:
This approach is illustrated by the patient presenting with chest pain (CP). A
majority of the patients rule out for acute myocardial infarction (AMI),
including patients with indigestion, shortness of breath, and other clinical
findings. This is the basis for an emergency department (ED) CP observation unit
to reduce coronary care unit admission rates. When the Goldman algorithm for
discharging low-risk patients with CP from the ED using only clinical features
and electrocardiographic findings proved difficult to implement, we turned to
measuring the diagnostic efficiency of a new cardiac marker to replace the
evolutionary changes in creatine kinase (CK) isoenzyme MB. The physicians making
the decision were blinded to the results of the study. We fitted the expected
characteristics of the test to the expected results for our program. The test was
done on the presenting specimen of 293 evaluable patients with a median of 6.5
hours from the time of onset of CP to the time the specimen was drawn. The result
was compared with the evolutionary pattern of CK-MB. RESULTS: The sensitivity of
the test at presentation to the ED was 85% compared with < 50% for the presenting
CK-MB, the false negative results taken earlier than 3 hours or 10 days after the
onset of symptoms. Troponin-T effectively identifies non Q-wave AMI much earlier
than the CK-MB. This study led to a prospective randomized clinical trial to
demonstrate an improved medical and financial benefit from an early rule in or
rule out of severe coronary artery ischemia. CONCLUSION: The study supports our
hypothesis that the laboratory can systematically redesign its technology
strategy and participate in the construction of a clinical pathway for the
discharge from ED or admitting decisions with a test 98% sensitive for
identifying patients with serious coronary ischemia by 3.5 hours after the onset
of symptoms.
PMID- 10184886
TI - Training students for the continuum: call for collaboration.
PMID- 10184887
TI - GPOs celebrate end to FASA price list extension (for now).
PMID- 10184888
TI - The Goals of Medicine Conference: bringing the issues to the field.
PMID- 10184889
TI - Quality 101. Part 1.
PMID- 10184890
TI - Build a data warehouse to make IT investments pay off.
PMID- 10184891
TI - Is your organization ready for open access?
PMID- 10184892
TI - More health plans relying on specialists as gatekeepers.
PMID- 10184893
TI - L.A. County learns costly lesson on mandated labor guidelines.
PMID- 10184894
TI - A cooperative methodology to build conceptual models in medicine.
AB - We designed a methodology to perform distribute activities on conceptual
modelling among cooperating centers. Our methodology assigns responsibilities and
tasks and regulates interactions preserving coherence; it passes through the
construction of unambiguous paraphrases to make explicit the context within the
original sources, and through their compositional representation in an
intermediate language. The process is intrinsically iterative, with continuous
feedbacks and refinements, alternating analytic view on details and synthetic
view on regularities and structures. Our methodology is based on requirements and
experience made in the first GALEN project, and was applied in the GALEN-IN-USE
project to coordinate modelling activities of three teams of surgeons in Rome
with activities of other partners, during the production of an extensive model of
surgical procedures.
PMID- 10184895
TI - On different roles of natural language information in medicine.
AB - In this paper the authors analyze the main different function types of language
in medical environment in different communicative situations and descriptive
tasks. These functions are categorized as knowledge transfer, documentation,
directive function, expression of emotions. The computer representation of the
information have to be different according to the different tasks. The paper
highlights the most important differences and concludes that further research is
necessary in the details.
PMID- 10184896
TI - The Read Thesaurus--creation and beyond.
AB - The creation of the Read Thesaurus was a unique undertaking, involving over 2000
clinicians. This clinically-led, multidisciplinary enterprise posed many
organisational and professional challenges. The process of term collection and
integration and the problems encountered are described. A brief account is given
of the large task of maintenance and refinement. This paper looks at the
practical and cultural aspects and describes how problems were tackled by good
organisation, clear guidelines and much goodwill.
PMID- 10184898
TI - A second generation of terminological systems is coming.
AB - Diverse achievements by recent computer-based terminological systems are
outlining a new generation of systems (i.e. a "second generation"). We collected
the relevant features of various advanced terminological systems and we
systematized these features into four components of a unique framework. We review
a set of systems according to our framework, and we discuss how standardization
activities can support the evolution of computer-based terminological systems
towards a complete set of new performances.
PMID- 10184897
TI - A formal model of diabetological terminology and its application for data entry.
AB - This paper summarises the developmental activities for an electronic patient
record system in diabetology based on GALEN technologies. It focusses on the
modelling of primarily terminological medical knowledge of this subspecialty and
describes its application for predictive data entry.
PMID- 10184900
TI - What's in a name?
PMID- 10184899
TI - Virtual reality techniques in the treatment of impotence and premature
ejaculation.
PMID- 10184901
TI - Information technology needs of subacute care providers increase with market
changes.
PMID- 10184902
TI - Breast cancer--new health outcomes and accountability.
PMID- 10184903
TI - Heart teams share ideas for rapid improvements at forum.
PMID- 10184905
TI - Community care: a suitable case for treatment?
PMID- 10184904
TI - Cardiac team is on a mission for efficiency.
PMID- 10184906
TI - Part II--IEPS Reports. The proper function of teaching hospitals within health
systems.
AB - The main points of the discussions from the international seminar organised by
the World Health Organisation and the Institute for the Study of Health Policies
(IEPS) were published in French by Flammarion Medecine-Sciences in the Collection
entitled "The IEPS Reports" and in English by the WHO under the title "The Proper
Function of Teaching Hospitals within Health Systems" (1995).
PMID- 10184907
TI - Hyperlinked Lexicon in Nursing Informatics--a tool for navigating through Nursing
Informatics Terminology.
AB - The Evolution of Information Technology is rapid. Electronic circuits substitute
mental activities and new Technology invades to all aspects of life. Nursing,
which is like all the other Health related professions information-intensive,
could use the new Technology to be facilitated. The implementation of Informatics
to Nursing was supported by the growing information that Nursing has to manage.
The definition of Nursing Informatics was put on 1980 and since then a lot
attempts to define Nursing Informatics have followed. The applications of Nursing
Informatics are focused on four fields of Nursing: Administration of Nursing,
Clinical Practice, Education, and Research. The first applications of Nursing
Informatics made visible the need for the development of a Unified Language
System. The efforts, today, are focused on two fields: to establish a standard
definition of the terms of or related to Nursing Informatics, to establish
standard definitions and Classification Schemes for the Nursing Phenomena and
Practice so that they can be processed by Nursing Informatics. In solving these
problems important role plays the study of Linguistics. Another important factor
that should be taken into account is the Development of International Standards
of general acceptance that enhances communication aspects. Apart from the
International Standardisation Organisations, other non-profit organisations have
constituted Special Groups that are dealing with the promotion of Nursing
Informatics. Final Nursing Informatics should follow the previous attempts of
Nursing to establish a Unified Language System. All the steps of the development
of the application are described. In particular subjects that are covered are:
the scope of the application, the collection of the material, the designing and
building up of the Database, the development of a User Interface and the
characteristics of the Application.
PMID- 10184908
TI - The 3rd Users and Policymakers Group Workshop.
PMID- 10184909
TI - The 2nd Developers and Multimedia Group Workshop.
PMID- 10184910
TI - The 4th Users and Policymakers Group Workshop.
PMID- 10184911
TI - U.S. District Court invalidates HCFA's construction of the Pickle Amendment.
PMID- 10184912
TI - Wisconsin limits withdrawal of treatment from patients under guardianship. Spahn
v. Eisenberg.
PMID- 10184914
TI - Proceedings of the 2nd Year Conferences and Workshops of the NIGHTINGALE Project.
PMID- 10184913
TI - Healthcare at Kitty Hawk.
PMID- 10184915
TI - Publishing on the World Wide Web.
PMID- 10184916
TI - Medical Informatics Europe '97. Conference proceedings.
PMID- 10184917
TI - Data watch. What are the trends in emergency department visits related to drugs?
PMID- 10184918
TI - Good names. Market research reveals semantic differences in common health care
names.
AB - Using a research technique that combines a quantitative method adapted from
linguistic science and conventional qualitative methods, the authors explore
consumers' understanding of key terms--"primary care" vs. "family care,"
"hospital" vs. "medical center," and "aesthetic" vs. "cosmetic"--used in names
for health care services. Their results reveal semantic differences that clearly
point to names that optimally position these medical services in the local and
regional marketplace.
PMID- 10184919
TI - Hope and hyperbole: the rhetoric and reality of managerial reform in health care.
AB - The scope of this essay is broad--the dangers that much conventional management
commentary represents for health care institutions and those who work in them. It
emphasizes two themes in the hype and hyperbole of management talk about health
care. The first is the character of the language used to describe health care
arrangements--the 'rhetoric of medical managerialism'--a rhetoric that powerfully
and misleadingly combines the jargon of modern management schools with the
marketing hype of advertising. Second, it includes some observations about what
this cautionary tale might mean for the daily work of those in health care.
PMID- 10184920
TI - U.S. senator agrees that federal government has gone too far, pledges to work
with GHA.
PMID- 10184921
TI - Securing coverage in a competitive environment. Read v. Medical X-Ray Center.
PMID- 10184922
TI - Scientific basis of health services.
PMID- 10184923
TI - The impact of health economics on health policy and practice.
PMID- 10184924
TI - Scientific bases versus scientism in health services.
PMID- 10184925
TI - Clinical practice guidelines for heart failure.
AB - Development of guidelines can be a difficult process; each organization or
institution must establish the rules and criteria for including specific
therapies and the level of complexity needed. Specific outcomes must be
incorporated, including maintenance of comfort and functionality, freedom from
hospitalization, and survival. In existing guidelines for the management of heart
failure, angiotensin-converting enzyme (ACE) inhibitor therapy is clearly the
gold standard. However, there is still a high mortality with ACE inhibitor
therapy; the key may be choosing the right patients. Current guidelines reflect
the uncertainty regarding digoxin before the Digitalis Investigation Group (DIG)
trial; obviously, these guidelines should be revisited. Clinical practice
guidelines for the management of heart failure need to be revised to include a
better consensus on beta-blockade, the new data on digoxin, emerging data on
angiotensin II receptor antagonists, and current thinking on anticoagulant
therapy.
PMID- 10184926
TI - Cost of heart failure to the healthcare system.
AB - From an economic, mortality, and functional standpoint, heart failure is clearly
a disease that needs to be targeted. We can develop a model for heart failure to
determine the impact that specific management strategies will have on the overall
cost to the system, which by itself can tell us some interesting things because
we're currently spending twice as much on transplantation as on digoxin therapy.
We can then use this model to assess the impact of different strategies, such as
greater use of angiotensin-converting enzyme (ACE) inhibitors or digoxin therapy.
PMID- 10184927
TI - Heart failure and disease management.
AB - Disease management is a comprehensive program that identifies a population of
patients at risk, provides a coherent framework of coordinated care for these
patients, and demonstrates improved outcomes. In applying disease management
strategies to heart failure, there is clearly the technology to improve outcomes.
The two main issues involved are influencing physician practice patterns and
improving patient compliance. A successful disease management program in heart
failure should include patient identification patient assessment, patient
education and training, patient monitoring, and triage and acute intervention.
With the advances in treatment of heart failure, we have the means to keep
patients out of the hospital, maintain their functionality, and decrease
mortality. The real issue, which is where disease management can help, is how to
apply technology in an effective way to turn potential gains into real gains. The
key is not to develop more technology, but to implement effectively the
technology that exists.
PMID- 10184928
TI - Touring the future of medicine.
PMID- 10184929
TI - Proposal: a position for the insurance industry on genetic testing.
AB - Proposed legislation to limit the use of genetic test results in insurance
underwriting has appeared with increasing frequency at the state and federal
level. The proponents seek to protect consumers from unfair discrimination by
insurers. Can we not develop a proactive approach, acknowledging that we do not
need to do prospective testing while we assert that we must retain the current
status of equivalency of information between the underwriter and the applicant?
PMID- 10184930
TI - The future of surgical tissue adhesives.
AB - This guest editorial commentary outlines both the background and probable future
developments of surgical tissue adhesive use in the United States and highlights
the contributions made by the authors of this issue of the Journal of Long-Term
Effects of Medical Implants. In addition, several issues specifically relevant to
fibrin tissue adhesives in the United States are addressed. These include
commercially available fibrin sealants and blood bank-produced products, as well
as the proper nomenclature for such materials.
PMID- 10184931
TI - Labelling medical devices: still waiting for the defining moment.
AB - Recent developments in labelling and use of symbols are reviewed in this article
together with the issues still being debated. Different symbols for the same
concept continue to be a concern as well as the definition of the symbol for
"sterile" for terminally sterilized devices. The essential message is that there
is still some way to go before the requirement are totally clear.
PMID- 10184932
TI - Coronary heart disease in the United States.
PMID- 10184933
TI - Primary prevention.
PMID- 10184934
TI - Secondary prevention.
PMID- 10184935
TI - Methods and mindsets in pharmacoeconomics.
PMID- 10184936
TI - Issues and controversies in pharmacoeconomics.
PMID- 10184937
TI - Pharmacoeconomics perspectives: payers, providers, and patients.
PMID- 10184939
TI - ORYX: problems arise with reporting infections.
PMID- 10184938
TI - "Hire" education: lessons for IT execs.
PMID- 10184940
TI - Joint Commission's ORYX may have data flaws.
PMID- 10184941
TI - Writing for staff, employees, patients, and family members. Know your audience.
PMID- 10184942
TI - Proceedings of Medicine Meets Virtual Reality 6. San Diego, California, USA.
January 28-31, 1998.
PMID- 10184943
TI - Towards Meaningful Laboratory Tests for Evaluation of Pharmaceutical Aerosols.
Proceedings of the International Society for Aerosols in Medicine focus
symposium. Puerto Rico, January 29-31, 1997.
PMID- 10184944
TI - Carve outs and related models of contracting for specialty care: framework and
highlights of a workshop.
PMID- 10184945
TI - The economic functions of carve outs in managed care.
AB - This paper considers the economic functions of contracting separately for a
portion of the insurance risk, offering both the payer's (i.e., employer's) and
the health plan's perspective. Four major forms of carve outs are discussed: (1)
payer specialty carve outs from all health plans; (2) payer specialty carve outs
from only indemnity and preferred provider organization arrangements; (3)
individual health plan carve outs to specialty vendors; and (4) group practice
carve outs to specialty organizations. The paper examines whether carving out
care fosters the payer's goal of delivering reasonable healthcare efficiently,
how adverse selection affects the provision of healthcare, and the costs of
providing this specialized care.
PMID- 10184946
TI - Carve outs: definition, experience, and choice among candidate conditions.
AB - Despite increasing discussion of carve outs as a device for controlling costs and
improving quality of care, little systematic information exists on the effects of
carve outs on cost, quality, and access to healthcare services. In the absence of
such information, a conceptual framework is useful for deciding which conditions
and populations may benefit from carve-out strategies, and how such arrangements
should be designed. After carefully defining carve outs, and distinguishing them
from other similar arrangements, this paper identifies five characteristics of a
healthcare condition that increase the likelihood that a carve out's benefits
will outweigh its drawbacks. The paper also examines the advantages and
disadvantages of alternative approaches to structuring and administering carve
out arrangements, including how to pay for services, how to integrate them with
mainstream care, provisions for consumer choice and provisions for carve-out
accountability. The piece concludes that population carve outs, in which all the
healthcare problems of a group of patients are managed by the carve-out
organization, have inherent advantages, and identifies candidate conditions for
population carve outs.
PMID- 10184947
TI - High court backs broad COBRA coverage. Geissal v. Moore Medical Corp.
PMID- 10184948
TI - Atypical antipsychotics and formulary decisions.
AB - Although drug costs are a small fraction of the total direct costs of treating
schizophrenia, managed care has focused on drug acquisition costs as an area of
concern. There is pressure to demonstrate by outcome measures that the increased
cost of the newer atypical antipsychotics versus traditional neuroleptics is
justified. Decision makers want to be convinced that newer, more expensive
treatment translates to value. Evidence accumulated to date suggests that the
atypical agents are cost-effective. Studies show patients taking atypical
antipsychotics have an improved quality of life, are more easily rehabilitated
and reintegrated into the community, return to full- or part-time work more
often, and prefer the newer agents to conventional antipsychotics. These benefits
have been shown in studies of olanzapine versus haloperidol. Just as important,
patients taking atypical antipsychotics show decreased medical care resource
utilization, which results in cost savings.
PMID- 10184949
TI - Cyberhealth: hospitals online. Hospitals and health care organizations making the
most of Internet/intranet technology.
PMID- 10184950
TI - Hospital's failure to enforce policies held a basis for liability. Denton
Regional Medical Center v. LaCroix.
PMID- 10184951
TI - Privacy rights breached by pharmacy company. Washburn v. Rite Aid Corp.
PMID- 10184952
TI - Nancy-Ann Min DeParle: embrace change and quality.
PMID- 10184953
TI - Now, a scary strain of drug-resistant HIV.
PMID- 10184954
TI - New drugs blast budgets. Patients benefit; hospital pharmacies weigh options.
PMID- 10184955
TI - Arizona administrators learn people ABCs and how to add enthusiasm to dining.
PMID- 10184957
TI - Managed care theory versus managed care reality.
PMID- 10184956
TI - Exporting managed care: importing quality lessons.
PMID- 10184959
TI - Girding for compliance. HFMA initiatives target training as way to survive
scrutiny.
PMID- 10184958
TI - The role of nutrition screening and intervention programs in managed care.
AB - Nutrition screening and intervention programs provide managed care plans with an
opportunity to meet the needs of the increasing Medicare risk population.
Recently, representatives from various health plans came together to discuss
program benefits as well as the best practices in the development and
implementation of such programs to ensure successful outcomes. Through simple and
cost-effective programs, health plans can improve member satisfaction, resource
utilization, and the health status of their members.
PMID- 10184960
TI - Remember when ... doctors were doctors, not "providers"?
PMID- 10184961
TI - Lessons learned from capitation's heartland. Is California dreamin' a nightmare-
or a vision?
PMID- 10184962
TI - Appellate court restores apparent agency claim. Malanowski v. Jabamoni.
PMID- 10184963
TI - Court rules nurse not disabled. Thompson v. Holy Family Hospital.
PMID- 10184964
TI - Civil suit focuses on who is liable for residents.
PMID- 10184965
TI - Physicians should learn contracting language.
PMID- 10184966
TI - Lessons learned from capitation's heartland. Is California dreamin' a nightmare-
or a vision?
PMID- 10184967
TI - Delegation. Creating a balance among home care, the disability community,
regulators, and payors.
AB - Can the disability and the home care communities come together on the best way to
provide client-centered home care with an appropriate balance between patient
choice and provider liability? Should nurses be responsible and liable for all
nursing tasks provided in home settings? Or are there some tasks--such as
medication administration skin care, and even ventilator administration--that can
safely be performed by non-nurses? And if tasks can legally be performed by non
nurses, what is necessary to ensure that tasks are done safely?
PMID- 10184968
TI - Assembly provides opportunities for dialogue.
PMID- 10184969
TI - Meeting future sponsorship needs.
PMID- 10184970
TI - 83rd Catholic Health Assembly, June 7-10, 1998, held in New Orleans, Lousiana.
PMID- 10184971
TI - Consent form is not an enforceable contract and may be modified verbally. Kovacs
v. Freeman.
PMID- 10184972
TI - Woman in labor can withdraw consent for VBAC at any time. Schreiber v. Physicians
Insurance Company of Wisconsin.
PMID- 10184973
TI - Owner/operator of outpatient center may be liable for acts of independent
physician. Malanowski v. Jabamoni.
PMID- 10184974
TI - EMTALA does not apply to newborns. Lopez-Soto v. Hawayek.
PMID- 10184975
TI - Public policy exception available to employees terminated for reporting resident
abuse. Hausman v. St. Croix Care Center.
PMID- 10184976
TI - Incident reports protected from discovery and in camera review. Carr v. Howard.
PMID- 10184977
TI - Insurer may not limit coverage due to allegations of sexual misconduct. American
Home Assurance Co. v. Stephens.
PMID- 10184978
TI - Long hot summer ahead. Congressional speakers see vigorous discussions on
Medicare and managed care.
PMID- 10184979
TI - Compliance summit: hospitals see promise and challenges.
PMID- 10184980
TI - Unions play hardball, lawyers say.
PMID- 10184981
TI - The People's Health Network: a proto-PSO.
PMID- 10184982
TI - Beverly loses another case regarding the supervisory status of nurses; Eighth
Circuit Appeals Court sides with labor board/union.
PMID- 10184983
TI - Medical devices; effective date of requirement for premarket approval for three
class III preamendments devices--FDA. Proposed rule; opportunity to request a
change in classification.
AB - The Food and Drug Administration (FDA) is proposing to require the filing of a
premarket approval application (PMA) or a notice of completion of a product
development protocol (PDP) for the following three class III preamendments
devices: Lung water monitor, powered vaginal muscle stimulator for therapeutic
use, and stair-climbing wheelchair. The agency also is summarizing its proposed
findings regarding the degree of risk of illness or injury designed to be
eliminated or reduced by requiring the devices to meet the statute's approval
requirements and the benefits to the public from the use of the devices. In
addition, FDA is announcing the opportunity for interested persons to request
that the agency change the classification of any of the devices based on new
information. This action implements certain statutory requirements.
PMID- 10184984
TI - Hospital liable for unauthorized disclosure of patient records. Fairfax Hospital
v. Curtis.
PMID- 10184985
TI - Medicare and insurer fight over financial responsibility for transplant. Sentry
Insurance Employee Group Medical Plan v. Shalala.
PMID- 10184986
TI - Facts crucial to determine what constitutes the practice of medicine.
PMID- 10184987
TI - Trusts--payment or distribution of proceeds of trust property: categorizing a
trust for the purpose of determining eligibility for medical assistance. Hecker
v. Stark County Social Service Board, 527 N.W. 2d 226 (N.D. 1994).
PMID- 10184988
TI - A modern LOINC (Logical Observation Identifier Names and Codes).
PMID- 10184989
TI - Untangling the vocabulary of the World Wide Web.
PMID- 10184990
TI - Hot news on fire codes from NFPA's annual meeting.
PMID- 10184991
TI - Supreme Court's decision leaves key questions unanswered.
PMID- 10184993
TI - Hedge against downsizing: numbers you need to know.
PMID- 10184992
TI - Managing IAQ (indoor air quality).
PMID- 10184995
TI - CPT codes: creating a common language.
PMID- 10184994
TI - Despite losses in budget process, AHA/GHA made significant gains.
PMID- 10184996
TI - Intravenous immune globulin for recurrent spontaneous abortion.
PMID- 10184997
TI - Future directions for research in laboratory medicine: the findings of a Delphi
survey of stakeholders.
AB - In July 1995, we asked 101 experts to anticipate future areas for research in
clinical laboratory medicine using a modified Delphi survey approach. The panel
included academicians, clinical laboratory professionals, laboratory managers,
practicing physicians public health officials, hospital administrators, and
representatives of manufacturing industries, managed care organizations,
commercial laboratories, and government health agencies. The participants
predicted fewer laboratories, more automation, and fewer skilled staff needed in
the future. The consensus was that laboratory quality assurance will focus on
patient outcomes and be benchmarked against peer groups. They agreed that quality
assurance routinely will be integrated into testing kits. Measures derived from
medical informatics, such as outcomes analysis and utilization statistics, will
become a standard feature of health care. A major area of concern was the effect
that reorganizing health care and striving for cost containment will have on
laboratory services. These views were consistent with those expressed by
participants at a CDC conference on the frontiers of laboratory medicine research
held shortly after the study was completed. These topics by now are familiar to
most laboratory professionals, and we urge them to explore the many research
issues raised with their colleagues in their clinical laboratories, health-care
organizations, and industry.
PMID- 10184999
TI - The role of reflexive (algorithmic) testing in laboratory medicine: adapting to
the new era.
AB - Centralized Laboratory Services, Inc. (CLS) is a large, freestanding laboratory
that is an affiliate of the Health Insurance Plan of New York, a managed care
organization with more than 1 million members in New York and New Jersey. The
laboratory work for this membership is consolidated at CLS, which thus serves an
ambulatory patient population. The Medical Director at CLS is charged with
optimizing laboratory utilization by clinicians who are part of the system.
PMID- 10185000
TI - Impact on human resources: Core Laboratory versus laboratory information system
versus modular robotics.
AB - Technological advances in laboratory systems have had a great impact on human
resources. Surviving the changes requires an in-depth understanding of the
technology to implement the appropriate operational model. St. Mary's is a 414
bed, acute care hospital. For 18 months, the laboratories went through the
process of moving from a noncomputerized traditional model laboratory (i.e., by
discipline) to a fully computerized Core Lab. The Core Lab concept fully
integrates biochemistry, hematology, blood bank, and microbiology into two
sections (not physically separated): tests processed by automation and tests
processed manually. This approach led to a 15% reduction in staff while the
volume doubled. The transitions occurred sequentially: from traditional
laboratory to Core Lab (noncomputerized), from manual Core Lab to fully
computerized Core Lab, and ultimately from a simulation of manual preanalytical
phase to automated preanalytical phase (modular robotics). The findings show that
Core Lab and computerization have almost the same impact on human resources, 35%
and 30% respectively, and modular robotics the least impact with 17%.
PMID- 10184998
TI - CLMA research initiative: moving into the 21st century with leadership in
knowledge. CLMA Research Advisory Committee.
PMID- 10185001
TI - Using the absolute neutrophil count as a stand-alone test in a
hematology/oncology clinic: an abbreviated test can be preferable.
AB - More is not always better. We hypothesized that clinicians prefer an abbreviated
but focused test to one that provides more--but not totally essential-
information. We performed a retrospective analysis of physicians' ordering
practices after introducing the absolute neutrophil count (ANC) as a stand-alone
test in a hematology/oncology clinic. Previous studies have demonstrated a strong
correlation between the ANC, as determined by the Coulter STKS instrument, and
the manual neutrophil count. In contrast to the more extensive five-part
differential the ANC is a one-part differential that focuses exclusively on the
neutrophil count and provides abbreviated information. The hematology
laboratory's records from 2 months before and 4 months after introducing this new
test were analyzed. Total numbers of ANCs, automated complete differentials, and
manual complete differentials performed were tabulated. After its introduction,
the ANC comprised more than 75% of differentials performed in this clinic. Manual
complete differentials dropped from 69.4% to 18.8%. The turnaround time (TAT) for
all differentials taken together dropped by 75% (p = 0.042). We conclude that the
ANC can be used widely in the hematology/oncology clinic as a separate, stand
alone test. For clinicians, its popularity over the five-part differential may be
based on the fact that the ANC is a focused test with a relatively short TAT. Our
experience suggests that it is the test result's relevance and not the volume of
information provided that determines clinicians' use.
PMID- 10185002
TI - Key performance indicators to assess laboratory operations. Action-packed
benchmarking with HBSI (HBS International Inc.).
AB - The first article of this series highlighted the five most widely used
performance measurement systems for comparing laboratory and clinical department
operations. This column has since taken an in-depth tour of two of the systems,
the MECON PEERx and the Laboratory Management Index Program. We also have taken a
slight detour to discuss the ORYX initiative, which has been mandated for certain
types of health-care organizations accredited by the Joint Commission. In this
issue we return to a more detailed analysis of one of the five most commonly used
benchmarking systems for clinical services, HBS International, Inc.
PMID- 10185003
TI - Retaining key staff, Part I.
PMID- 10185004
TI - Enhancing decision-making effectiveness in problem-solving teams.
AB - Active participation by all group members as well as the generation,
presentation, and critical evaluation of a wide range of perspectives and
alternatives are hallmarks of effective problem-solving teams. Diverse groups
with an odd number of participants (five to seven members are generally best) are
manageable and provide an adequate range of perspectives and alternatives.
Several problems limit the effectiveness of problem-solving teams. Dysfunctional
concurrence or "groupthink" occurs when concurrence seeking in cohesive groups
overrides the realistic appraisal of alternative courses of action. Managers
initially should withhold their own opinions, assign members the role of critical
evaluators, and bring in people from outside the initial group to minimize this
problem. Domination by a select few is also a problem because it can squelch the
presentation of diverse opinions. Brainstorming and nominal group technique can
mitigate this problem. In nominal group technique, a manager guides the group
through steps involving brainstorming, recording, and voting on the merits of
various alternatives before open discussion is allowed. Decision-making dropouts
are group members who withdraw from active participation in the group. Managers
can reduce this problem by emphasizing the importance of active participation and
by monitoring performance.
PMID- 10185005
TI - The gray zone.
AB - Think for a minute about the terms equivocal and indeterminate. Equivocal is
defined as "of uncertain significance", and indeterminate is defined as
"indefinite, uncertain". Now think of the context in which laboratory results are
reported: either by using the exact words equivocal or indeterminate or cloaked
in technical jargon (e.g., cytologic diagnoses "ASCUS" or "AGUS"). Clinicians
expect (or at least want) laboratory results to be black or white (i.e.,
bimodally distributed), whereas laboratorians strive for the perfect shade of
gray because of data that often are bimodal but overlapping. A consequence of
this color war is "the gray zone" (often confused with the "twilight zone"), a
noncommittal zone that leaves laboratorians and clinicians alike plenty of wiggle
room, allowing us to interpret results on either side of the fence. This article
examines the root causes of the gray zone, with several clinical examples of how
it permeates laboratory interpretation.
PMID- 10185006
TI - As we see it. Hang together and you may not hang at all.
PMID- 10185007
TI - Do no harm versus the greatest good for the greatest number: health care and the
clash of ethical imperatives.
AB - For two millennia, more or less, doctors all over the world have taken the
Hippocratic oath to "do no harm." However, these words often have conflicted with
social policy. Particularly in this century, some governments and other
institutions have encouraged--or insisted on--placing the good of the state ahead
of the duty to individual patients. Sterilizing "handicapped" and "feebleminded"
persons in Germany long before the creation of the concentration camps is a
prominent example of a program initiated under the guise of sacrificing few to
improve the welfare of all. America likes to think it is fundamentally different
from the Germany that carried out the sterilization program. However, the social
and economic forces in Germany that placed national health above the principle of
do no harm and encouraged doing the greatest good for the greatest number are
similar to what is developing in America--a concordance between economic forces
and a social philosophy that is willing to curtail access of some individuals to
treatments that they need, want, and can pay for to achieve a hypothetical goal
of better national health.
PMID- 10185008
TI - Portfolio 2000: managing clinical systems.
AB - Powerful forces are changing the provision of health care. Management is
transitioning into new responsibility for a leaner, more flexible, customer
focused operation to support the goals of integrated systems of the 21st century-
to minimize disease and to promote health. In response to this evolution, the
clinical systems management concept describes multidimensional competencies,
which are transportable throughout the continuum of care (1). These new knowledge
competencies and core competencies applied in a different context are
characterized in this paper.
PMID- 10185009
TI - Proactive management in the managed care era.
AB - Preparing for the future impact of managed care on clinical laboratories remains
a complex challenge as the corporate strategies of health maintenance
organizations (HMOs) and managed care contracting continue to evolve. Employers
often fail to use data or quality measures to select an HMO, preventing a
clinical laboratory from competing on patient care issues. Developing analysis
skills and knowledge concerning physician ordering data, HMO information, costs,
and capitation rate corridors prepares the enterprise and managers for a
successful future.
PMID- 10185010
TI - Clinical integration: one health-care system's experience.
AB - Clinical integration is occurring continuously in most health-care environments.
Depending on the process and model used, outcomes have varied. Success depends on
strong leadership, careful planning, and continuous communication. Within health
care systems, further integration is occurring with service consolidation among
hospitals in geographic proximity. Such consolidation is financially driven.
These various changes reflect the new "quantum mechanics" of health-care
management. In quantum thinking, the management process involves viewing systems
as a large set of relationships, interdependent and interrelated. It is a new age
of increasing complexity.
PMID- 10185011
TI - Critical pathways: design, implementation, and evaluation.
AB - As David M. Eddy, M.D., Ph.D., Senior Advisor for Health Policy and Management to
Southern California Kaiser Permanente, discusses in his excellent book, Clinical
Decision Making: From Theory to Practice (1), we are now in a time where we must
rethink what we are doing and how we are doing it. Substantial variations among
physicians in almost every aspect of the diagnostic process have been documented
repeatedly, and these variations appear to cause patients to be treated
differently. Eddy says these variations are not the fault of physicians or anyone
else because of the complexity of the medical decision process. Nonetheless, the
cost and quality of health care have suffered as a result. Numerous articles and
individuals such as Jay McDonald, M.D., Professor and Chair of the Department of
Pathology at the University at the University of Alabama at Birmingham Medical
Center, also have highlighted these variables in practice patterns and their
consequences (2). Dr. Eddy, Dr. McDonald, Michael G. Bissell, M.D., Ph.D.,
Director, Clinical Pathology, Allegheny General Hospital, Pittsburgh,
Pennsylvania, and other leaders in the field have stressed the need for more
standardization of health care; clinical decisions concerning diagnostic testing
and therapeutic choices must be based on scientific evidence that demonstrates
the practice being used is truly effective (1-6). This evidence, as well as other
parameters discussed below, are known as outcomes. As expressed by Dr. McDonald,
"there is a transition that is going on from doing what seems best to doing what
one knows is best" (2). Practice guidelines and critical pathways now are seen by
many as one solution to providing more standardization of health care and to
meeting the demands of the rapidly changing medical environment for
simultaneously increasing the quality of care while decreasing the costs.
PMID- 10185012
TI - Integrating laboratory processes into clinical processes, Web-based laboratory
reporting, and the emergence of the virtual clinical laboratory.
AB - References to integration occur frequently in the health-care literature.
Integration in this context refers to the blending or merging of the separate
components of a health-care organization to form a cohesive and seamless
interoperating whole. The health-care industry is now in the process of
reorganizing and consolidating through hospital mergers and the creation of
provider networks. The stimulus for these activities, all integrative, has been
the introduction of managed care as a replacement for fee-for-service
reimbursement. Managed care was designed to introduce competition into health
care delivery, and it certainly has succeeded in this goal. The quest for
integration in health care is thus a consequence of the shift to managed care and
has been driven by the belief that integration will lead to greater efficiency
and cost savings in the industry. The major vehicles for achieving integration in
the clinical laboratories will be Web-based reporting and the emergence of the
virtual clinical laboratory.
PMID- 10185013
TI - Robotics, automation, and the new role of process control.
AB - The natural progression of automation in the clinical laboratory next will lead
to robotic devices to perform many of the manual tasks still remaining. To date,
most efforts of laboratory automation have been directed at the analytic phase.
New targets for automation will be at the preanalytic and postanalytic phases
where many of the bottlenecks in specimen flow now occur in highly repetitive
manual tasks. Laboratory professionals will have a unique opportunity to
incorporate new concepts of robotics in their facilities to improve error rates
and to use massive laboratory databases to improve medical and public health
services.
PMID- 10185014
TI - Standardization across multiple sites.
AB - Standardizing products, procedures, and processes in clinical departments across
multiple sites has significant potential for improving clinical outcomes,
enhancing financial savings, and simplifying management processes. This is true
whether a network of owned hospitals is working toward a full-scale clinical
integration or a group of community hospitals is collaborating to gain cost
efficiencies. By developing a functional team and designing a relatively simple
program, the results can be very rewarding. The author describes some of the
basic principles in designing a standardization program and cites some examples
of successful programs as well as listing some pitfalls to be avoided along the
way.
PMID- 10185015
TI - Optimizing point-of-care testing in clinical systems management.
AB - The goal of improving medical and economic outcomes calls for leadership based on
fundamental principles. The manager of clinical systems works collaboratively
within the acute care center to optimize point-of-care testing through systematic
approaches such as integrative strategies, algorithms, and performance maps.
These approaches are effective and efficacious for critically ill patients.
Optimizing point-of-care testing throughout the entire health-care system is
inherently more difficult. There is potential to achieve high-quality testing,
integrated disease management, and equitable health-care delivery. Despite rapid
change and economic uncertainty, a macro-strategic, information-integrated,
feedback-systems, outcomes-oriented approach is timely, challenging, effective,
and uplifting to the creative human spirit.
PMID- 10185016
TI - Telemedicine: emerging opportunities and future trends.
AB - Remote location, lack of specialty services, or managed care capitation
contribute to limited access to health care. As reimbursement rates decline,
availability to expert or high-tech care is affected. The need to "make do" with
available personnel, existing technologies, or dated facilities is not uncommon
and affects the quality of health care. Telemedicine accounts for these issues
and serves as an alternative to providing interactive evaluation and management
of patients. As computer hardware and software improve and become less costly,
access to this technology will be more commonplace and establish itself as an
acceptable standard of practice. The Internet may serve as a highway to resources
that currently are not available in rural areas or in third-world countries.
Access to Web sites that provide comprehensive and instructive material is just
one part of a complex, developing area of health care.
PMID- 10185017
TI - Legal basis and interpretations of medical necessity.
AB - This article examines the legal issues surrounding medical necessity in Medicare
reimbursement. The author reviews how the Health Care Financing Administration
has defined medical necessity for laboratory testing and the role of the
laboratory and the laboratory manager in ensuring medical necessity.
PMID- 10185018
TI - Integrated ethics for the clinical systems manager.
AB - This article describes how clinical systems managers can integrate clinical
ethics, management ethics, and the social responsibility of business or
organizational leaders (business ethics) to resolve ethical dilemmas they may
encounter. Three examples are discussed: policy on use of resources, personnel
issues, and managed care and the current backlash against it.
PMID- 10185019
TI - As we see it. Compliance: back to the future.
PMID- 10185020
TI - Wisdom circles.
AB - King Arthur had the right idea all along--to get the key stakeholders around a
table and address the vital issues. The author describes his concept of a "wisdom
circle," a gathering of people who speak candidly and from the heart, listen
intently to the wisdom of other people, and honor the wisdom and intelligence we
all possess to meet both individual and collective needs.
PMID- 10185021
TI - Violence in the health care environment. Risky business, Part 1.
PMID- 10185022
TI - A summary of fraud and abuse issues affecting clinical research programs.
AB - In an environment where the health care industry is under unprecedented scrutiny,
it is important for all of those involved in the delivery of patient care and
clinical research to be aware of and adhere to government grant requirements and
billing practices. Fraud and abuse violations, no matter how minor they may seem,
can result in substantial consequences for the grantee institutions and the
investigators themselves.
PMID- 10185023
TI - Pace yourself! A step-wise approach to full clinical automation.
PMID- 10185024
TI - Laser show. Lovelace Health Systems finds alternative solution to bandwidth
problem.
PMID- 10185025
TI - The Doylestown shuffle. Nine steps to a successful application upgrade.
PMID- 10185026
TI - Leaving your legacy. Choosing a centralized or decentralized client/server
architecture depends on your business objectives.
PMID- 10185027
TI - Pain for trying. Physician scheduling software is a high yield investment.
PMID- 10185028
TI - Before you see smoke. Late testing your systems for Y2K problems? So's everyone
else. Here's what to do about it.
PMID- 10185029
TI - Life in the fast lane. Hardware systems in the next millennium must be able to
simultaneously compute and analyze both operational and outcomes data.
PMID- 10185030
TI - Doing the right thing. While HIPAA's ends are noble, its means are hotly
disputed. Meanwhile, time is running out.... Interview by Charlene Marietti.
PMID- 10185031
TI - Line by line. Minnesota is actively participating in review and comment on
proposed HIPAA regulations.
PMID- 10185033
TI - Home healthcare. The times, they are a changin'.
PMID- 10185032
TI - Wire you waiting? Wireless LAN technology delivers on promises of flexibility and
mobility now--and more is yet to come.
PMID- 10185034
TI - No sour notes. Five ways to hammer out harmony between your IS professionals and
users.
PMID- 10185035
TI - And the winner is ... telemedicine award winners bring specialized healthcare to
rural areas.
PMID- 10185036
TI - The money trap. Four pitfalls of contract management system integration and how
to avoid them.
PMID- 10185037
TI - The fine art of managing up. A CIO primer for tying together business and IT
strategies.
PMID- 10185038
TI - Cramming for comparisons.
PMID- 10185039
TI - Embrace change, reap value. How successful organizations make their IT
investments count.
PMID- 10185040
TI - Uncle Sam wants you. U.S. TAG (Technical Advisory Group) sets future course on
standards.
PMID- 10185041
TI - Bullet-proof warehouses.
AB - Organizational transformation, complex reporting requirements and growing respect
for evidence-based medicine are driving data warehousing implementations. But the
current dearth of health-care-specific applications and turnkey systems still
makes the data warehouse a custom project.
PMID- 10185042
TI - Stone soup. When providers and vendors together throw their ideas into the pot,
the IT infrastructure that results can satisfy them both. Interview by Polly
Schneider.
PMID- 10185043
TI - Ready for prime time? Object-oriented technologies are coming to healthcare, [but
they're not ready for prime time--yet].
PMID- 10185044
TI - Different paths, one destination.
PMID- 10185045
TI - Physician practice management systems. Practice makes panic?
PMID- 10185046
TI - Recent developments in reading therapy: a review of the literature.
AB - This paper defines the term 'reading therapy' and discusses its early development
in the United Kingdom and the USA. A review of the recent literature in the field
is followed by some recommendations on the implementation of reading therapy in
health and community care libraries.
PMID- 10185047
TI - Challenges and strategies in getting evidence-based practice into primary health
care--what role the information professional?
AB - Recent years have seen a drive towards evidence-based practice in health care,
whereby decisions are made based on the best available evidence from research.
Concerning the drive towards a primary care-led NHS, this article examines the
particular features of primary care, with reference to recent literature, which
may mean that an evidence-based approach is more difficult to achieve than it is
in secondary care. Initiatives underway that attempt to address some of these
difficulties are highlighted, and the future role of the information professional
in achieving the adaptation of evidence-based practice in primary health care is
considered. This article has been developed from a presentation given at Under
One Umbrella 4, UMIST, on 29 June 1997.
PMID- 10185048
TI - Becoming ADEPT (Applying Diagnosis, Etiology, Prognosis, and Therapy Programme):
delivering distance learning on evidence-based medicine for librarians.
AB - Evidence-based medicine (EBM) brings new challenges and opportunities for
librarians. However, their ability to respond to this agenda is constrained by
their difficulties in acquiring the requisite new skills and techniques while
continuing to work in a busy information practice setting. The authors describe a
joint initiative, between a specialist evidence-based healthcare information unit
and a regional library network, to deliver training materials using a mixed
workshop and distance learning format. The Applying Diagnosis, Etiology,
Prognosis, and Therapy filters (ADEPT) Programme draws upon research conducted at
McMaster University, Canada and, using techniques adapted from the teaching
evidence-based medicine paradigm, seeks to equip health care librarians with the
skills and techniques required to support evidence-based practice locally. The
authors describe the thinking behind the programme, its main features, the
extensive evaluation mechanisms incorporated into the course, the results of the
evaluation and the lessons learnt. They conclude with a description of the way
forward for participants on the programme who are adapting their newly acquired
knowledge to their work situations. Further planned developments from the
course's designers are also outlined briefly.
PMID- 10185049
TI - The roles of library liaisons in a problem-based learning (PBL) medical school
curriculum: a case study from University of New Mexico.
AB - The relationships between problem-based learning (PBL) curricula and libraries
have generated a substantial number of journal articles, but few have addressed
the importance of the interaction between health science libraries and PBL
curricula. This article attempts to contribute to this dimension through a
description of the roles of library liaisons. First we describe the evolution of
the liaison roles beginning 2 years prior to the implementation of a PBL
curriculum. We then describe the core responsibilities of liaisons at the
University of New Mexico (UNM) with mention of other innovative roles developed
by some liaisons.
PMID- 10185051
TI - Overcoming network barriers: the implementation of the NISS BIOMED Service in the
Trent NHS Region.
PMID- 10185050
TI - Connecting Anglia & Oxford to core health information.
PMID- 10185052
TI - What do health professionals think of their library service? Report of a multi
professional user satisfaction survey.
PMID- 10185053
TI - Psychiatric disabilities and the Americans with Disabilities Act: implications
for policy and practice.
AB - People with psychiatric disabilities are often victims of job discrimination. The
Americans with Disabilities Act (ADA) of 1990 makes it very clear that job
discrimination based on a psychiatric impairment is illegal. The Equal Employment
Opportunity Commission (EEOC) reports that psychiatric disability is one of the
leading causes why persons file discrimination complaints. Given this situation,
an analysis is offered of what constitutes a psychiatric disability under the
ADA. An overview, an analysis, and examples of the kinds of accommodations
employers can be expected to provide people with psychiatric disabilities are
offered. The policy and practice implications of the employment provisions (Title
I) in the area of psychiatric disabilities are presented.
PMID- 10185054
TI - Variation in psychotropic drug use in nursing homes.
AB - Numerous studies of health service use reveal considerable variation in the
degree of services provided. In this article the variation in psychotropic drug
use in nursing homes is examined. First, a descriptive analysis of nursing homes
with and without high levels of psychotropic drug use is provided. Second, an
analysis of the determinants of high levels of psychotropic drug use in nursing
homes is provided. Factors such as ownership, staffing levels, having special
care units, case-mix intensity, competitiveness of the nursing home market, and
the state Medicaid reimbursement rate structure are examined. The results of
these analyses are discussed in terms of their policy issues.
PMID- 10185055
TI - Health promotion for the elderly persons in Hong Kong.
AB - By the year 2000, there will be one million elderly persons in Hong Kong. With
the rise of an older population, the cost of health care is likely to increase.
Studies conducted in Hong Kong have shown that over 30% of health care
expenditure is spent on the elderly. Unless steps are taken to slow the onset of
chronic illnesses in elderly people, health care expenditure will increase
rapidly in the future. The present paper describes strategies that have been
adopted for promoting a healthier elderly population in Hong Kong. The paper also
reports the results of an evaluative study on the largest health promotion
program for older people in Hong Kong. It seems to show that health promotion
activities may have the potential to save lives, delay institutionalization, and
improve life satisfaction.
PMID- 10185056
TI - Health for all: is there health parity between blacks and whites?
AB - Although various health care policies and health-promoting efforts by individuals
have created a climate for healthy living, minorities still face higher health
risks than Whites; this is especially true for Black Americans. The latest data
show Blacks are especially vulnerable to a variety of preventable diseases and
premature deaths. The findings show that they are better off than Whites on only
two out of 18 health indicators examined. This paper presents several strategies
to promote healthier living for Black Americans.
PMID- 10185057
TI - Alternative treatments of cancer: trends over time and implications for the
future.
AB - There has been increasing utilization of alternative treatments for cancer,
affected primarily by the dissatisfaction of the public with the outcomes of
conventional treatments. Mortality rates from cancer have been increasing over
time while spending by government on conventional cancer research rose. The lack
of clinical trials on alternative therapies has left them open to criticism by
mainstream medicine. Pharmaceutical companies have not funded trials because of
an anticipated negative result to their profits. The government also has not
shown much interest in research on alternative treatments although large
expenditures on conventional treatments have not produced successful results.
There is substantial evidence to support effectiveness of alternative therapies,
based primarily on retrospective studies and case studies. Recently, clinical
trials have been initiated with government approval, for a few alternative
therapies; and such government involvement would improve the information
available on treatments, to the benefit of the public.
PMID- 10185058
TI - Commercial health insurance enrollment.
PMID- 10185059
TI - The medical records confidentiality issue: an overview.
PMID- 10185060
TI - Mission to Brazil: a surgical perspective.
PMID- 10185061
TI - In their own words. The CPT (Current Procedural Terminology) Editorial Panel.
PMID- 10185062
TI - HCFA's proposed rule on resource-based practice expenses.
PMID- 10185063
TI - An omen for American physicians? A look at Britain's National Health Service.
PMID- 10185064
TI - An insider's look at the role of the carrier medical director: an interview with
Patrick Price, MD, FACS. Interview by William F. Seward.
PMID- 10185065
TI - Is a Third-World mission right for you?
PMID- 10185066
TI - Wanted: world-class surgeons.
PMID- 10185067
TI - Private contracting.
PMID- 10185068
TI - Creating a service culture has improved patient satisfaction at east Texas's 165
bed Brazosport Memorial Hospital.
PMID- 10185069
TI - The National Committee for Quality Assurance has updated a brochure which helps
consumers assess the quality of health plans.
PMID- 10185070
TI - Computerized patient records aren't much good if doctors don't use them. Here's
how one hospital got its physicians online.
PMID- 10185071
TI - OSF-St. Mary Medical Center in Galesburg, IL, has landed a prestigious award for
its total quality management strategy.
PMID- 10185072
TI - Statewide collaborative. Vermont program targets a few key interventions.
PMID- 10185073
TI - Performance measurement. It's all about "team-ness".
PMID- 10185074
TI - An incident reporting system: documented at the point of service.
AB - Many healthcare organizations maintain two systems for documenting incidents
reports: A paper incident report system completed by staff and managers and A
computerized system where clerical staff duplicate the same information in a
database. This article discusses the way risk managers in hospitals and
healthcare organizations can reduce paperwork and more rapidly address the
implementation of a point of service computerized system to document incidents.
The benefits of such a system include: Real-time information and trending of
occurrences. Reduced liability by securing reports earlier. Maintaining a higher
level of confidentiality. Earlier problem resolution. Providing a valuable link
between the risk, quality, and safety functions of the organization.
PMID- 10185075
TI - Risk management through staff education.
AB - The staff members of a healthcare organization are recognized as students of risk
management. The risk manager, through application of the fundamentals of
andragogy (i.e., learning strategies specific to adult learners), is in an
advantageous position to assist staff in successfully applying risk management
thought processes and related actions.
PMID- 10185076
TI - Flood disaster preparedness: a retrospect from Grand Forks, North Dakota.
AB - Natural disasters often come without warning. The clinical, financial, and
business risks can be enormous. Grand Forks' (ND) healthcare systems experienced
a flooding disaster of unprecedented proportions in April of 1997. Planned and
practiced disaster and evacuation procedures can significantly reduce a
healthcare facilities' risk to life, health, and safety. This article
retrospectively analyzes disaster preparation and the complete evacuation of the
facilities' patients.
PMID- 10185077
TI - Four indefensible phlebotomy errors and how to prevent them.
AB - The author identifies four errors in phlebotomy that are effectively indefensible
in a court of law: patient misidentification, improper angle of insertion,
improper vein selection, and ineffective training and evaluation of those
performing venipunctures. Strategies to avoid these errors include the
implementation and enforcement of specific administrative and procedural
policies. A side bar on the "Ten Commandments of Phlebotomy Liability"
accompanies this article.
PMID- 10185078
TI - Pharmaceutical risk management: special problems encountered in the hospital
setting.
AB - This article (1) reviews the types of adverse drug reactions that can occur, (2)
discusses liability issues for hospitals and healthcare professionals who
practice in a hospital or nursing home setting, and (3) presents risk management
strategies for maximizing the quality of pharmaceutical care while minimizing
exposure to risk.
PMID- 10185079
TI - Practice guidelines. Guidelines admissible to show standard of care. Frakes v.
Cardiology Consultants, P.C.
PMID- 10185080
TI - Pedicle screws. Lack of FDA approval does not implicate use in hospital.
PMID- 10185081
TI - False Claims Act. Qui tam plaintiff must have standing to sue. U. S. ex rel.
Riley v. St. Luke's Episcopal Hospital.
PMID- 10185082
TI - Violations of fraud and abuse regulations not necessarily false claims. U.S. ex
rel. Thompson v. Columbia/HCA Healthcare Corp.
PMID- 10185083
TI - Hospital erred in disclosing claimant's medical records. Fairfax Hospital v.
Curtis.
PMID- 10185084
TI - Hospital may be liable in spite of due care exercised by agents. Denton Regional
Medical Center v. LaCroix.
PMID- 10185085
TI - Positive action. Here's what to do when a load goes bad.
PMID- 10185086
TI - Secondhand woes? The FDA takes a new look at refurbished devices; users consider
the implications.
PMID- 10185087
TI - Bid-rigging: it happens. An antitrust primer for procurement professionals.
PMID- 10185088
TI - Downsizing takes a holiday.
PMID- 10185089
TI - Don't needle me. Team reduces patient sticks for IVs, blood draws.
PMID- 10185090
TI - Beware the 'discount' repair vendor! This 16-point test will keep you from
getting gouged.
PMID- 10185092
TI - Stats. Does reengineering pay off? The jury's still out.
PMID- 10185091
TI - Putting the 'value' in value analysis.
PMID- 10185093
TI - A week in the life of a hospital.
AB - The same urgency and intellect that America's teaching hospitals apply to saving
lives is now also going into saving the institutions themselves. All across the
country, academic medical centers are trying to figure out how to marry progress
with profits. At the Duke University Medical Center, TIME visits the front line
in the war between money and medicine.
PMID- 10185095
TI - Against all odds: air medical transport in India.
PMID- 10185094
TI - New order of things: an international overview of air medical transport.
PMID- 10185096
TI - Think before you act: a national survey of interhospital transfer policies and
practices.
AB - INTRODUCTION: As health care evolves, air medical program (AMP) interhospital
transfers will come under increasing scrutiny. The object of this study was to
evaluate various components of the interhospital transfer policies of AMPs across
the country. METHODS: A structured telephone interview of the chief flight nurse
(CFN) or administrator of 90 geographically selected AMPs was conducted by a
college-educated research assistant using a scripted questionnaire. RESULTS:
Seventy-seven (86%) of the AMPs contacted agreed to answer the questionnaire. CFN
or administrator unavailability was the reason for nonresponse. The mean number
of flights performed per year was 1046: 29% scence and 71% interhospital
missions. Mission profile ranged from fixed-wing (19), rotor-wing (45), and both
(13). Forty-five percent of respondents require prior administrative approval and
31% require prior medical approval before accepting an interhospital mission.
Financial approval or long distance transport was the most common reason for
requiring approval. Ninety-four percent of programs transferred patients to
facilities other than the AMPs' host hospital; two-thirds of these programs
required medical (30%) or administrative (35%) authorization before accepting
missions. CONCLUSION: This survey indicates that most AMPs use some form of
screening mechanism for interhospital flight requests. With managed care
requiring health care delivery systems to examine the use of resources, AMPs
should continue to stay ahead of trends that affect the industry.
PMID- 10185097
TI - Air medical transport of the injured patient: scene versus referring hospital.
AB - INTRODUCTION: In a rural service area, does the outcome of air medical patients
transferred from the scene of injury differ from that of patients transferred
from a primary receiving hospital? METHODS: Retrospective review of all injured
patients transported by air to a single trauma center during calendar year 1996.
Data collected include basic patient demographics, time of injury, revised trauma
score (RTS), injury severity score (ISS), probability of survival (PS), hospital
length of stay (LOS), complications, disposition, and mortality. RESULTS:
Concerning trauma admission, 594 of 1461 (40.7%) were transported by air: 363
from the scene (24.9%) and 231 from referring hospitals (15.8%). These two groups
were similar in demographics, injury severity, hospital LOS, and crude mortality:
RTS, 6.61 versus 6.68 (P > 0.05); ISS, 16.0 versus 16.0 (P > 0.05); LOS = 6.9
days versus 7.3 days (P > 0.05); mortality = 11.8% versus 10.8% (P > 0.05). The
groups differed significantly, however, in time from injury to definitive care
(34.2 minutes versus 196.2 minutes, P < 0.001), overall complication rate (39.1%
versus 57.6%, P = 0.009), and potentially preventable deaths (PS > 0.5, 11.6%
versus 44%, P = 0.02). CONCLUSION: Patient groups were similar, suggesting
similar triage criteria. Patients transferred from a referring hospital took
almost six times longer to reach definitive care and may have suffered an
increased morbidity and mortality on this basis.
PMID- 10185098
TI - Evaluation of retention of safety and survival training content versus industry
standard for training.
AB - INTRODUCTION: The accepted standard in the industry for survival and safety
training is annual recurrent educational programs. The industry has never looked
at nor tested content comprehension or retention on this subject. We decided to
conduct a sample testing of crews' ability to understand and retain survival
training material. METHODS: This study solicited the participation of four
program crews that had received previous training in safety and survival. A test
on safety and survival training content was administrated to nurses and
paramedics before a refresher course (test 1), then immediately after the course
(test 2), and again 6 months later (test 3). Ninety-six crew members took tests 1
and 2, and 79 (82%) took test 3. RESULTS: The average time since any crew member
participating in this study had attended a survival course was 1 to 1.5 years.
The pretraining test mean score was 60 (60%); the posttraining average score was
92 (92%); and the 6-month mean score was 65 (65%). CONCLUSION: Flight crews do
not retain a safe level of survival skill knowledge with annual recurrent
training. Therefore the industry needs to reevaluate its position on this
standard of annual recurrent training. Survival training is too important for
flight crews to undertake only once per year. Rescuer care is as important as
patient care.
PMID- 10185099
TI - Family member ride-alongs during interfacility transport.
AB - INTRODUCTION: A significant portion of the Air Med Team (AMT) flight missions
involves interfacility transport of the ill or injured to receiving facilities
with comprehensive resources available for their care. In an effort to help meet
the psychologic needs of our patients and their families, AMT developed a Family
Member Ride-Along program that allows family members or significant others to
accompany patients during interfacility transport. The purpose of this study was
to evaluate the ride-along program from the perspective of the family member
passenger (FMP) who has accompanied a patient during transport. METHODS: Thirty
one family member ride-alongs responded to a 10-item questionnaire using a scaled
response. Questions were designed to evaluate the benefit of the ride-along
program to patients and family members from the FMP perspective. RESULTS: All
FMPs surveyed thought the program was beneficial to either themselves or the
patients. Several benefits described by FMPs included the ability to offer
emotional support to the patient, provide patient information to receiving
physicians, and sign releases for medical treatment. During interfacility
transports, FMPs did not hinder either patient care or transport safety.
CONCLUSION: Our study shows that allowing FMPs to accompany patients during
transport benefits both patients and family members.
PMID- 10185100
TI - Business principles for air medical professionals. Part 3: The business plan:
cornerstone of success.
PMID- 10185101
TI - Provider sponsored organizations: a critical assessment.
PMID- 10185102
TI - Strategic visioning and cardiovascular leadership: turning vision into reality.
PMID- 10185103
TI - The making of a multipurpose, OR-ready, angiography/interventional cath lab
suite.
AB - The field of clinical cardiology is now poised to benefit from recent
technological advances. Potential for expanding services, increasing
productivity, and controlling costs is now awaiting the clinical cardiology. At
the same time, certain treatment therapies once addressed exclusively through
surgery are being replaced by less invasive procedures performed by
interventional cardiologists and radiologists as well as surgeons.
PMID- 10185104
TI - Cardiovascular physiology as a basis for clinical and financial outcomes.
AB - This article examines a test program that requires documentation of clinical
outcomes before reimbursement will be issued. The battle between financial
responsibility and clinical success at any cost is being driven by many
influences, and health care professionals are in the middle.
PMID- 10185105
TI - Echocardiography laboratory accreditation.
AB - In response to the need for standardization and improvement in the quality of
echocardiographic laboratories an intersocietal commission has been created. The
intent of the accreditation process is designed to recognize laboratories that
provide quality services and to be used as an educational tool to improve the
overall quality of the laboratory.
PMID- 10185106
TI - Quality 101, Part 3. The Malcolm Baldrige Award.
PMID- 10185107
TI - Outcomes assessment and disease management strategies in diagnostic imaging:
creating value and quality with nuclear cardiology.
AB - Noninvasive testing in cardiology may be used to control the initial diagnostic
costs as well as to limit expensive testing to only those at highest risk.
Outcome data may be used to profile accuracy for individual laboratories to
assure quality of the nuclear test data in altering patient management.
PMID- 10185108
TI - Developing an outpatient ventricular assist device program to meet the needs of a
"too successful" heart transplant program.
AB - The VAD independent living program has clearly demonstrated that a traditional
inpatient population can be successfully moved to an outpatient setting. Such a
move can result in significant cost savings for the institution while increasing
patient satisfaction. By moving the assist device patients to an outpatient
facility, we improved the overall operational efficiency of the Medical Center
and the MIMCU. Because of the overwhelming success of this project, the Medical
Center's administration has become receptive to the benefits of exploring
alternative outpatient care delivery systems. Faced with increased demands to
decrease operational expenses cardiovascular managers must restructure service
line programs and explore opportunities to move traditional inpatient care
delivery systems to outpatient settings.
PMID- 10185109
TI - The emerging role of enhanced external counterpulsation in cardiovascular disease
management.
PMID- 10185110
TI - The white coat syndrome.
PMID- 10185111
TI - A case for involuntary coverage.
PMID- 10185112
TI - A new way to downsize.
PMID- 10185113
TI - The price you pay for the drug not taken.
PMID- 10185114
TI - The new direction in disability management.
PMID- 10185115
TI - Don't let migraine be a financial headache.
PMID- 10185116
TI - Your Y2K survival guide.
PMID- 10185117
TI - Redefining dental coverage.
PMID- 10185118
TI - Coloradans tame the guidelines beast.
PMID- 10185119
TI - Datawatch. Rx coverage and consumer ads: a costly combo.
PMID- 10185120
TI - Designing programs for women employees.
PMID- 10185121
TI - Seven steps to corporate support for women's wellness.
PMID- 10185122
TI - Myths and realities of menopause.
PMID- 10185123
TI - The value of women's wellness programs.
PMID- 10185124
TI - Between the lines of the GOP bills.
PMID- 10185125
TI - Alternative care and ERISA erosion.
PMID- 10185126
TI - Can't survive on work alone.
PMID- 10185127
TI - The brave new reality of telemedicine.
PMID- 10185128
TI - PPMCs (physician practice management companies). What happens when doctors flock
together.
PMID- 10185129
TI - Choosing and using a benefits consultant.
PMID- 10185130
TI - Comparing health plans: the search for consensus.
PMID- 10185131
TI - The truth about hospice.
PMID- 10185132
TI - DataWatch. A helping hand for juggling work and family.
PMID- 10185133
TI - Learning from tragedies.
PMID- 10185134
TI - Consumer health information services cannot work alone.
PMID- 10185135
TI - Clinical indicators: do we know what we're doing?
PMID- 10185136
TI - Appropriate prescribing in general practice: development of the indicators.
PMID- 10185137
TI - Disseminating information about healthcare effectiveness: a survey of consumer
health information services.
AB - BACKGROUND: In 1997 a research based information leaflet designed for men
considering being screened for prostate cancer was distributed to general
practitioners (GPs) and consumer health information services. OBJECTIVES: To
investigate consumer health information service staff opinions of the leaflet and
the use they made of it. To find out whether such staff would find similar
leaflets on other topics useful. DESIGN: A postal questionnaire survey sent to
United Kingdom consumer health information services. RESULTS: Consumer health
information service staff were enthusiastic about the content and presentation of
the leaflet and gave it to many enquirers, including some who had not been given
information by their GPs. Respondents were keen to be supplied with similar
leaflets about different topics. Some respondents were reluctant to give the
leaflet to people enquiring about screening for prostate cancer, for example,
because they thought that the leaflet would cause anxiety, or because prostate
cancer screening was not freely available locally. CONCLUSION: Consumer health
information services can complement information provided by health professionals
and make good use of research based information for consumers. However, they may
withhold information from some people who might benefit from it and are not well
placed to advise people about healthcare options. Strategic thinking is needed to
encourage a more integrated approach to giving information and support for
patients in making decisions.
PMID- 10185138
TI - Indicators of the appropriateness of long-term prescribing in general practice in
the United Kingdom: consensus development, face and content validity,
feasibility, and reliability.
AB - OBJECTIVES: To develop valid, reliable indicators of the appropriateness of long
term prescribing in general practice medical records in the United Kingdom.
DESIGN: A nominal group was used to identify potential indicators of
appropriateness of prescribing. Their face and content validity were subsequently
assessed in a two round Delphi exercise. Feasibility and reliability between
raters were evaluated for the indicators for which consensus was reached and were
suitable for application. PARTICIPANTS: The nominal group comprised a
disciplinary mix of nine opinion leaders and prominent academics in the field of
prescribing. The Delphi panel was composed of 100 general practitioners and 100
community pharmacists. RESULTS: The nominal group resulted in 20 items which were
refined to produce 34 statements for the Delphi exercise. Consensus was reached
on 30, from which 13 indicators suitable for application were produced. These
were applied by two independent raters to the records of 49 purposively sampled
patients in one general practice. Nine indicators showed acceptable reliability
between raters. CONCLUSIONS: 9 indicators of prescribing appropriateness were
produced suitable for application to the medical record of any patient on long
term medication in United Kingdom general practice. Although the use of the
medical record has limitations, this is currently the only available method to
assess a patient's drug regimen in its entirety.
PMID- 10185139
TI - Mammography: influence of departmental practice and women's characteristics on
patient satisfaction: comparison of six departments in Norway.
AB - OBJECTIVE: To investigate how departmental practice and women's characteristics
are related to low patient satisfaction with mammography. DESIGN: Survey of
patients by means of self administered questionnaires before and after
mammography. PATIENTS: 488 women (89% of those invited), aged 23-86 years, at six
departments. MAIN OUTCOME MEASURES: Low level of satisfaction measured on
psychometric scales of physical pain, psychological distress, staff punctuality
and technical skills, information provided, and physical surroundings. RESULTS:
Satisfaction varied by department on the scales for pain, punctuality,
information, and surroundings. After adjustment for women's characteristics an
attributable risk of negative outcome by department was identified on the scales
for pain, distress, punctuality, information, and surroundings. Adjusted odds
ratio (ORs) ranged from 0.3 (95% confidence interval (95% CI) 1.2 to 6.0) on the
pain scale, to 6.0 (2.9 to 12.3) on the punctuality scale. After adjustment for
confounding variables, higher risk of dissatisfaction was associated with age <
50, nervousness about mammography, expected pain, lack of knowledge about
mammography, and distrust in mammography (adjusted OR (95% CI) ranged from 1.6
(1.0 to 2.7) to 3.7 (2.0 to 7.3)). CONCLUSION: Departmental practices differed
for breast compression, information, punctuality, and facilities and were
associated with a low level of satisfaction irrespective of patient
characteristics. Women's lack of knowledge about mammography and distrust in the
procedure were confirmed as risk factors for dissatisfaction. All these factors
might be helped by training the staff, improving facilities, and informing the
women.
PMID- 10185140
TI - Health authority commissioning for quality in contraception services.
AB - OBJECTIVE: To compare the commissioning of contraception services by London
health authorities with accepted models of good practice. DESIGN: Combined
interview and postal surveys of all health authorities and National Health
Service (NHS) trusts responsible for running family planning clinics in the
Greater London area. MAIN OUTCOME MEASURES: Health authority commissioning was
assessed on the presence of four key elements of good practice--strategies,
coordination, service specifications, and quality standards in contracts--by
monitoring activity and quality. RESULTS: Less than half the health authorities
surveyed had written strategies or service specifications for contraception
services. Arrangements for coordination of services were limited and monitoring
was underdeveloped. CONCLUSION: The process of commissioning services for
contraception seems to be relatively underdeveloped despite the importance of
health problems associated with unplanned pregnancy in London. These findings
raise questions about the capacity of health authorities to improve the quality
of these services through the commissioning process.
PMID- 10185141
TI - Enabling the implementation of evidence based practice: a conceptual framework.
AB - The argument put forward in this paper is that successful implementation of
research into practice is a function of the interplay of three core elements--the
level and nature of the evidence, the context or environment into which the
research is to be placed, and the method or way in which the process is
facilitated. It also proposes that because current research is inconclusive as to
which of these elements is most important in successful implementation they all
should have equal standing. This is contrary to the often implicit assumptions
currently being generated within the clinical effectiveness agenda where the
level and rigour of the evidence seems to be the most important factor for
consideration. The paper offers a conceptual framework that considers this
imbalance, showing how it might work in clarifying some of the theoretical
positions and as a checklist for staff to assess what they need to do to
successfully implement research into practice.
PMID- 10185142
TI - Trust in performance indicators?
AB - The 1980s and 90s have seen the proliferation of all forms of performance
indicators as part of attempts to command and control health services. The latest
area to receive attention is health outcomes. Published league tables of
mortality and other health outcomes have been available in the United States for
some time and in Scotland since the early 1990s; they have now been developed for
England and Wales. Publication of these data has proceeded despite warnings as to
their limited meaningfulness and usefulness. The time has come to ask whether the
remedy is worse than the malady: are published health outcomes contributing to
quality efforts or subverting more constructive approaches? This paper argues
that attempts to force improvements through publishing health outcomes can be
counterproductive, and outlines an alternative approach which involves fostering
greater trust in professionalism as a basis for quality enhancements.
PMID- 10185143
TI - Searching for information on outcomes: do you need to be comprehensive?
AB - The concepts of evidence-based practice and clinical effectiveness are reliant on
up to date, accurate, high quality, and relevant information. Although this
information can be obtained from a range of sources, computerised databases such
as MEDLINE offer a fast, effective means of bringing up to date information to
clinicians, as well as health service and information professionals. Common
problems when searching for information from databases include missing important
relevant papers or retrieving too much information. Effective search strategies
are therefore necessary to retrieve a manageable amount of relevant information.
This paper presents a range of strategies which can be used to locate information
on MEDLINE efficiently and effectively.
PMID- 10185144
TI - External evaluation of health care in Italy.
PMID- 10185146
TI - Practice made perfect.
AB - The perfect practice management system? Users say it is one that integrates
financial operational and clinical information within a practice, and at the same
time connects the practice to other parts of the organization.
PMID- 10185147
TI - Dreaming up new home care solutions.
AB - New prospective payment and outcomes assessment requirements--plus the ever
present need to run a business efficiently--are shaping home care information
technology solutions that emphasize data entry at the point of care.
PMID- 10185148
TI - Lives and livelihoods on the line.
AB - Linking telephone and computer technologies to deliver information can help a
health care organization accomplish strategic business goals: better customer
service and bottom line.
PMID- 10185145
TI - Management of lung cancer.
PMID- 10185149
TI - The CHIME/HMT CIO roundtable: wearing many hats.
PMID- 10185150
TI - What works. IT-packed mobile training center rolls through Texas, saving travel
expenses.
PMID- 10185152
TI - What works. Practice discovers new revenue stream using EMR (electronic medical
records).
PMID- 10185151
TI - What works. Going online saves health plan 50 percent first year.
PMID- 10185153
TI - Integrated outcomes: where CIOs need to be thinking.
AB - Financial data have been the mainstay in health care organization business
decision making. CIOs can lead efforts to add clinical and satisfaction data and
create more customer-focused integrated outcomes systems.
PMID- 10185154
TI - HotList: materials management systems.
PMID- 10185155
TI - Are you ready for HIPAA legislation?
PMID- 10185156
TI - IT and point-of-care decision support.
PMID- 10185157
TI - Internet marketing: software for the hard sell.
PMID- 10185158
TI - Systems integration at a higher level.
PMID- 10185159
TI - Are we really achieving IT value?
PMID- 10185160
TI - Emerging managed care technologies.
PMID- 10185161
TI - What works. Call center's emergency hotline set up in one hour.
PMID- 10185162
TI - What works. PPO saves three FTEs with case manager software.
PMID- 10185163
TI - What works. Telemedicine team work cuts transfer costs and generates new revenue.
PMID- 10185164
TI - HotList: document imaging.
PMID- 10185165
TI - CPT and HCPCS coding: the modifier fiasco.
PMID- 10185166
TI - Genomic torts: the law of the future--the duty of physicians to disclose the
presence of a genetic disease to the relatives of their patients with the
disease.
PMID- 10185167
TI - The need to know versus the right to know: privacy of patient data in an
information-based society.
PMID- 10185168
TI - New feudalism and the decline of libertarianism.
PMID- 10185169
TI - Justice and health care systems: what would an ideal health care system look
like?
AB - An 'ideal' health care system would be unencumbered by economic considerations
and provide an ample supply of well-paid health care professionals who would
supply culturally appropriate optimal health care to the level desired by
patients. An 'ideal' health care system presupposes an 'ideal' society in which
resources for all social goods are unlimited. Changes within health care systems
occur both because of changes within the system and because of changes or demands
in and by the 'exterior environment'. Social systems must be in a homeostatic
balance. If one component fails to accommodate itself to other forces, needs and
interests within the system, the system is imperiled. It is difficult to create a
just health care system in an unjust society, just as it is difficult to practise
truly ethical medicine in an ethically corrupt system.
PMID- 10185170
TI - Health care allocation, public consultation and the concept of 'health'.
AB - By comparing models of market-based allocation with state-controlled national
health care systems, it will be suggested that the way in which different
communities deal with the allocation of health care is central to their
expression of what might be called a moral self-understanding. That is to say
that the provision of health care may be expected to be a focus of communal
debate, not simply about morally acceptable and unacceptable actions, but also
about the community's understanding of what it is that makes for a worthwhile and
morally defensible human life. This moral self-understanding is seen to be
entwined with the different concepts of 'health' that are implicit in different
systems of allocation. In conclusion, it will be suggested that decisions
concerning health care allocation must be made in response to a continuing,
public and open debate about what health and health care mean to a particular
community.
PMID- 10185171
TI - The religious ideology of the Business Roundtable.
AB - The article is in two parts with the first part showing that the material in the
New Zealand Business Roundtable documents is consistent with the contemporary,
international, libertarian ideology. The second part draws parallels between this
material and the characteristics shown by religious movements, including a
claiming of authority from past prophets, a belief in an overarching Power, a
missionary zeal to convert others, a canon of texts, a 'theodicy', a sense of
bonding among believers, a 'doctrine' of humanity, and the use of ritual
language. The article concludes that the documents show a self-supporting belief
system built on a fallacious theoretical premise.
PMID- 10185172
TI - Health and efficiency: clinical effectiveness dissected.
AB - If the exclusive promotion of values inimical to our basic humanity extends to
the health care policy arena, we face a defensive, restricted, impersonal and
ultimately impoverished health care system. Americans known it already as
'managed-care'. This is why it is crucial for health policy analysts to make
explicit the role of values in policy-making, especially that involving the input
of 'value-neutral' economics. The nature of any clinical effectiveness policy
will be determined by the understanding of cost-effectiveness employed in its
design and implementation. Given that cost-effectiveness is nowadays usually
defined according to health economists' criteria, the battle over the meaning of
clinical effectiveness is a significant development in health economics' move to
assume control of the NHS.
PMID- 10185173
TI - The recovered memories debate: how reliable is the scholarship?
AB - The disputed issues that comprise the recovered memories controversy are so
important that they deserve the most careful and intellectually honest
scholarship that the academic and professional community can muster. Drawing
partly on illustrative material from the recent Health Care Analysis paper by
Goodyear-Smith et al. and associated commentaries, it is argued that the
controversy is not being well served. The rules of scholarship are too often
broken, with the result that the products are often superficial, containing what
should have been readily avoided factual errors, and are sometimes even
misleading.
PMID- 10185174
TI - In praise of scholarship: a reply to McCullough.
PMID- 10185175
TI - The question of resources and the application of disability rights.
PMID- 10185176
TI - Resource allocation for the mentally ill: a question of law and politics.
PMID- 10185177
TI - A dialogue concerning the philosophy of health care.
PMID- 10185179
TI - University hospitals prepare for the future.
PMID- 10185178
TI - Risk communication in the patient-health professional relationship.
PMID- 10185180
TI - The International Federation of Nurse Anesthetists (IFNA), an introduction.
AB - An introduction to the IFNA, its objectives and relationships. The definition, as
in the IFNA by laws of nurse anesthetist and a lsit on IFNA member countries and
different practice settings are discussed.
PMID- 10185181
TI - Involving private voluntary health care providers in 'Better Health for Africa'.
AB - In Sub-Saharan Africa private voluntary health care providers are mostly Church
related or social not for profit organizations. They provide between 40% and 60%
of health care services. In the context of Health Care Reforms, the World Bank
and others have (re)discovered these non governmental providers. The World Bank
document 'Better Health for Africa', promotes prominent roles for them in the
execution of basic package of services and public health tasks. Unfortunately,
the World Bank does not outline clearly how these roles should be achieved. The
danger exists that governments, under pressure to economize, will only take the
privatization angle which is in contradiction with the aims and objectives of the
not for profit private providers. Thus their potential to contribute to Public
Health care will be left unused and the reforms harder to achieve. My argument is
that the collaboration between government and NGOs should be approached in the
perspective of delegation of public duties and partnership. Thus the autonomy of
NGO providers can be respected while their technical capabilities can be used
optimally.
PMID- 10185183
TI - "All our tomorrows".
PMID- 10185182
TI - Build or remodel? Preparing facilities for today's and tomorrow's needs.
AB - As the site for the patient care moves from inpatient settings, hospitals face
major decisions about the future of their facilities. Those build in the 1970's
and early 1980's do not necessarily accommodate today's technology and patient
care equipment, not convert readily to outpatient space. Thus administrators face
the challenge of deciding what and how much to remodel in a facility, and what
should be new construction. Duke University Medical Center, which includes 1124
licensed inpatient beds, on campus clinics, and off-site primary care practices,
has faced such a challenge. In the past five years, administrators, clinicians,
and facility designers have systematically reviewed current facility status, and
planned renovations and new construction. All inpatient units were renovated in
less than two years. During this time, clinical services were maintained and
occupancy issues were managed. Space utilization, design and new technology
resulted in units better suited to the needs of patients, families and staff.
PMID- 10185184
TI - Quality management: the role of hospital boards.
AB - The changing social, political and economic environment has, for the first time,
forced hospitals to account for their financial performance. Hospitals have
responded to this demand by restructuring, downsizing and implementing
efficiencies. At the same time, professionals and consumers are becoming
increasingly concerned about the impact of rapid change on the quality of
hospital care. In this context, the challenge for all stakeholders is to
explicitly outline who is responsible and accountable for assuring high quality
hospital care. The purpose of this paper is to discuss the role of hospital
boards in relation to quality improvement. A framework currently used by a
metropolitan Canadian teaching hospital, to assure continuous quality improvement
despite significant budget cuts, is outlined.
PMID- 10185185
TI - Civilian Health and Medical Program of the Department of Veterans Affairs
(CHAMPVA)--VA. Final rule.
AB - This document amends the medical regulations concerning medical care for
survivors and dependents of certain veterans. These regulations establish basic
policies and procedures governing the administration of the Civilian Health and
Medical Program of the Department of Veterans Affairs (CHAMPVA), including
CHAMPVA claims processing procedures, benefits and services.
PMID- 10185186
TI - Occupational exposure to bloodborne pathogens: request for information--OSHA.
Request for information.
AB - OSHA requests information and comment on engineering and work practice controls
used to eliminate or minimize the risk of exposure to bloodborne pathogens due to
percutaneous injuries from contaminated needles and o ther contaminated sharps in
occupational environments. Percutaneous injuries continue to be a concern in work
settings where employees are exposed to bloodborne pathogens. The Agency is
considering possible actions that it can undertake to assist in addressing this
issue. Consequently, OSHA is interested in strategies for reducing percutaneous
injury rates that have been successfully implemented in the work environment,
including work practices and, in particular, the use of devices designed to limit
the risk of such injuries. The information received in response to this notice
will be carefully reviewed and will assist OSHA in determining effective
approaches to reducing percutaneous injury rates and what role the Agency may
have in these approaches.
PMID- 10185187
TI - Interim rule amending Summary Plan Description regulation--Department of Labor.
Interim rule with request for comments.
AB - This document contains an interim rule amending the information required to be
contained in the Summary Plan Description (SPD) required to be furnished to
employee benefit plan participants and beneficiaries under the Employee
Retirement Income Security Act of 1974, as amended (ERISA). Specifically, this
rule amends the information required to be disclosed in the SPD with respect to
the Newborns' and Mothers' Health Protection Act of 1996. The amendment contained
in this document will affect group health plan sponsors, administrators,
fiduciaries, participants, and beneficiaries.
PMID- 10185188
TI - Proposed amendments to Summary Plan Description Regulations--Department of Labor.
Notice of proposed rulemaking.
AB - This document contains proposed amendments to the regulations governing the
content of the Summary Plan Description (SPD) required to be furnished to
employee benefit plan participants and beneficiaries under the Employee
Retirement Income Security Act of 1974, as amended, (ERISA). These amendments are
being proposed to implement information disclosure recommendations of the
President's Advisory Commission on Consumer Protection and Quality in the Health
Care Industry, as set forth in their November 20, 1997 report "Consumer Bill of
Rights and Responsibilities," by clarifying benefit, medical provider and other
information required to be disclosed in, or as part of, the SPD of a group health
plan and for other reasons as well. This document also contains a proposed
amendment to repeal the limited exemption with respect to SPDs of welfare plans
providing benefits through qualified health maintenance organizations (HMOs). In
addition, the Department is proposing a number of amendments to the SPD content
regulation that are intended to update and clarify the application of provisions
affecting both pension and welfare benefit plans. The amendments contained in
this document will affect employee pension and welfare benefit plans, including
group health plans, as well as administrators, fiduciaries, participants and
beneficiaries of such plans.
PMID- 10185189
TI - Employee Retirement Income Security Act of 1974; rules and regulations for
administration and enforcement; claims procedure--Department of Labor. Notice of
proposed rulemaking.
AB - This document contains a proposed regulation revising the minimum requirements
for benefit claims procedures of employee benefit plans covered by Title I of the
Employee Retirement Income Security Act of 1974 (ERISA or the Act). This proposed
regulation would establish new standards for the processing of group health
disability, pension, and other employee benefit plan claims filed by participants
and beneficiaries. In the case of group health plans, as well as certain plans
providing disability benefits, the new standards are intended to ensure more
timely benefit determinations, improved access to information on which a benefit
determination is made, and greater assurance that participants and beneficiaries
will be afforded a full and fair review of denied claims. If adopted as final,
the proposed regulation would affect participants and beneficiaries of employee
benefit plans, plan, fiduciaries, and others who assist in the provision of plan
benefits, such as third-party benefits administrators and health service
providers or health maintenance organizations that provide benefits to
participants and beneficiaries of employee benefit plans.
PMID- 10185190
TI - International conference on harmonisation; guidance on statistical principles for
clinical trials; availability--FDA. Notice.
AB - The Food and Drug Administration (FDA) is publishing a guidance entitled "E9
Statistical Principles for Clinical Trials." The guidance was prepared under the
auspices of the International Conference on Harmonisation of Technical
Requirements for Registration of Pharmaceuticals for Human Use (ICH). The
guidance is intended to provide recommendations to sponsors and scientific
experts regarding statistical principles and methodology which, when applied to
clinical trials for marketing applications, will facilitate the general
acceptance of analyses and conclusions drawn from the trials.
PMID- 10185191
TI - Medicare and Medicaid programs; quarterly listing of program issuances--first
quarter, 1998--HCFA. Notice.
AB - This notice lists HCFA manual instructions, substantive and interpretive
regulations, and other Federal Register notices that were published during
January, February, and March of 1998 that relate to the Medicare and Medicaid
programs. It also identifies certain devices with investigational device
exemption numbers approved by the Food and Drug Administration that may be
potentially covered under Medicare. Section 1871(c) of the Social Security Act
requires that we publish a list of Medicare issuances in the Federal Register at
least every 3 months. Although we are not mandated to do so by statute, for the
sake of completeness of the listing, we are including all Medicaid issuances and
Medicare and Medicaid substantive and interpretive regulations (proposed and
final) published during this timeframe.
PMID- 10185192
TI - A Medal of Honor winner's new mission.
PMID- 10185193
TI - The ailing AMA. The doctors' lobby is struggling to recruit members and retain
its status as a Washington powerhouse.
PMID- 10185194
TI - Medicare's exodus. Congress wants more of the elderly in HMOs, but many HMOs
don't want more elderly. They say they can't afford to provide benefits, and are
calling it quits.
PMID- 10185195
TI - The P.S. Project: improving the quality of life.
PMID- 10185196
TI - The mind and body connected: integrating behavioral health and primary care.
PMID- 10185197
TI - 1997 CBGP (Council of Behavioral Group Practices) benchmark survey: quality
management efforts in group practices.
PMID- 10185198
TI - An interview with Michael Hurst: from paper to PCs.
PMID- 10185199
TI - Dialogue. Prescription for problems? Capitating mental health drugs--the great
debate.
AB - With the issue of physician capitation far from being resolved, mental health
drug capitation is understandably up for debate. Those who deem it essential
point to the rising cost of mental health drugs and urge management techniques
which they believe can hold the delicate balance between a plan's budgetary
limitations and a patient's appropriate care. They suggest that with an
objectively calculated capitation rate, based not on expenditure alone, but on a
defined population and their care needs, providers will not have to choose
between profitability and optimal care. But others, responding to increasing
quality concerns under capitation, worry that the increasing use of formularies
will preclude patients and their providers from ready access to newer, more
effective medications. With advocates still striving for nationwide parity for
mental health benefits, capitating medications is not likely to assuage their
concerns. Driving the debate is the fact that new technology drugs are expensive
and most health plans are unable to anticipate the funding of breakthrough
pharmaceuticals. With the advent of marketing to consumers directly through
television and print media, plans and providers are increasingly pressured to
provide these medications. The recent clamor for Viagra is an excellent example
of how quickly the word can spread. New mental health medications may be even
more expensive and offer patients and their families greater effectiveness with
far fewer side effects. Plans, providers, and patients are caught in the middle,
each holding their distinct view of the problems and solutions. This issue's
dialogue brings our readers a discussion of capitation of pharmaceuticals as a
primary answer to the sharp rise in mental health drugs. Three points of view lay
out the viability and cautions of developing formularies and systems that could
keep costs under control while still providing patient access. Without question,
the debate will continue as legislative and consumer pressure continues to focus
on managed care's techniques for cost savings and patient management. More
sophisticated systems, designed for increasingly integrated and complex treatment
plans, are certain to be required in the future. However, decisions about how to
develop practice guidelines and integrate formularies with expensive new
pharmaceutical technology, must begin to take shape now.
PMID- 10185200
TI - Behavioral healthcare: delivering cost-effective reimbursable services.
PMID- 10185201
TI - Managed care and criminal justice experts confront issues at conference.
PMID- 10185202
TI - Lessons learned: collecting child and adolescent outcomes data.
PMID- 10185203
TI - Behavioral medicine in the mainstream primary care setting.
PMID- 10185204
TI - Lead, follow, then step aside. Partners for health in rural northern Michigan.
AB - In communities all across America, there is a new appreciation for the powerful
influence of society on the health and well-being of individuals and populations.
Concurrent to this growing belief that good health is made up of more than more
absence of illness is the certainty that more and more, the traditional health
care model has less and less to do with real health in a community.
PMID- 10185205
TI - Serving as citizen legislators.
PMID- 10185206
TI - New OIG and DOJ guidelines. Let the punishment fit the crime.
PMID- 10185207
TI - Learning to fly.
AB - This year marks the fifth anniversary of West Michigan Air Care, the first
merged, hospital-based air medical program in the United States. This milestone
is being observed with a certain satisfaction that comes from achieving what
others said "couldn't be done."
PMID- 10185208
TI - Consumers are driving change.
AB - Should hospitals, which have traditionally defined payers and physicians as their
customers, be concerned about issues of consumer interest? Evidence is growing
that consumers are redefining the formula of success for hospitals. Consider
these consumer-oriented changes made by some of the nation's leading health
organizations.
PMID- 10185209
TI - Ways to redefine health.
AB - Currently across the nation, hospitals and health systems are redefining health
to include a more global perspective. Countless communities are realizing that
building a healthy community is not merely the provision of health care to all
citizens, but the deliberate creation of health along multiple dimensions:
physical, emotional, social, environmental, educational, economic, cultural,
aesthetic and spiritual.
PMID- 10185210
TI - Creating a formidable force.
AB - An alliance between two of the state's premier health care institutions holds
promise that Michigan is heading toward the forefront as a national leader in
cancer research, prevention and patient care.
PMID- 10185211
TI - A zero tolerance for violence.
PMID- 10185213
TI - Clinical program integration: building strategic partnerships.
AB - Integrated delivery systems continue to form through hospital mergers. The basis
for the mergers and systems development as presented to hospital boards and the
community is to lower health care costs, and improve quality and access.
PMID- 10185212
TI - Maximizing Internet access.
PMID- 10185214
TI - Who lives across the street?
PMID- 10185215
TI - Ludwig Award winners. Community benefits demonstrated.
AB - This year, the MHA received 18 nominations for the Ludwig Community Benefit
Award, representing comprehensive programs to improve community health status
through collaboration and innovative approaches. Each entry is a winner in the
best sense--to win means to succeed, prevail or triumph--and that's what MHA
members across the state are doing, one community at a time. Five programs were
selected from four member organizations to receive the award.
PMID- 10185216
TI - Are they patients or customers?
AB - Imagine you could reduce complaints in your institution from 2.5 to .5 per 1,000
patient encounters, while simultaneously increasing patient compliments from .5
to 5.1 per 1,000 patients. Imagine that you could have 10 times as many delighted
customers as complainers. In fact, that's what happened at Inova Fairfax
Hospital's Department of Emergency Medicine, Falls Church, VA.
PMID- 10185217
TI - Building healthy communities... to help stop hunger.
AB - A one-of-a-kind program, Michigan Harvest Gathering units businesses,
foundations, and nonprofit agencies for the purpose of distributing emergency
food to those in need. Since it started in 1991, $1.9 million and 2.5 million
pounds of food have been raised and distributed.
PMID- 10185218
TI - Hospital CEOs share lessons. Successful partnerships build healthy communities.
PMID- 10185219
TI - Community benefits are key. A common link for effective integration.
AB - As the Michigan Health & Hospital Association leads the nation in the commitment
to build healthy communities, other organizations are becoming involved in many
different kinds of community initiatives with confusion and even conflict
resulting. With community concepts assuming a central role in local health care
reform, differing methodologies present major challenges in demonstrating
benefits to target communities.
PMID- 10185220
TI - Don't be caught napping.
AB - Private employers with 50 or more employees and all public employers are bound by
the Family Leave Act. These employers must extend 12 weeks (nonconsecutive) of
unpaid leave in a one year period for birth or adoption; care for a spouse, child
or parent; and the employee's own "serious health condition."
PMID- 10185221
TI - Leading by following.
AB - Hospitals and health systems have learned, from what we call the medicalization
of social problems, that many conditions are only treatable, no curable, by the
time they reach our doors. Medical efforts to solve substance abuse, poverty,
teen pregnancy, or violence are noble but, in the end, ineffectual.
PMID- 10185222
TI - What makes a healthy city?
PMID- 10185223
TI - PSO organizers find big I.T. investments essential.
AB - As providers consider creating health plans to offer services to Medicare
beneficiaries, some are discovering that the required investment in information
systems could make profitability tough to achieve.
PMID- 10185224
TI - Is there a doctor on the 'Net?
PMID- 10185225
TI - Year 2000 planning woeful, multiple studies conclude.
PMID- 10185226
TI - Reaching out to physicians.
AB - One of the nation's largest physician practice management companies is rolling
out to virtual private network to collect, analyze and disseminate outcomes data
to physicians via the Internet.
PMID- 10185227
TI - Telemedicine's advocate in Washington. Interview by Jennifer A. Gilbert.
PMID- 10185228
TI - Data entry on the run.
AB - An ambulance service in Louisiana equips medics with pen-tablet computers to
speed collection of accurate and complete information.
PMID- 10185229
TI - Strategies for clinics. How integrated delivery systems are applying automation
at their group practices.
AB - Integrated delivery systems that have created or acquired physician group
practices are attempting to determine the best way to apply information
technology at these sites. This involves standardizing on one practice management
system for all sites, determining the feasibility of installing electronic
patient records systems and expanding computer networks to accommodate the
exchange of data among outpatient as well as inpatient sites.
PMID- 10185230
TI - Preparing for the looming EDI standards mandates.
AB - Tucked away inside the Health Insurance Portability and Accountability Act of
1996 are administrative simplification provisions that could have profound
consequences for providers and payers alike at the turn of the century. Health
care organizations must prepare now to comply with the mandates for using
standards for electronic claims and related transactions. This special report
offers sound advice and also includes exclusive electronic claims statistics from
Faulkner & Gray's 1999 Health Data Directory.
PMID- 10185231
TI - Shift to electronic claims continues at a slow pace.
PMID- 10185233
TI - The new health information networks: CHINtranets.
AB - Organizers of the surviving community health information networks are gravitating
to Internet technologies as a way to hold down costs and make the networks easier
to use. This story analyzes the strategies of these survivors.
PMID- 10185232
TI - Physician data entry: providing options is essential.
AB - Getting doctors to enter data into computer-based patient records systems is a
challenge. Many physicians are resisting using any of the available options,
choosing instead to stick with dictating their notes for later transcription. To
build support among physicians for electronic records, many health care
organizations are placing a premium on identifying the easiest and most efficient
data entry methods.
PMID- 10185234
TI - Biotechnology: an overview of the tools, therapeutic agents, and applications to
pharmacy practice.
AB - The promise of pharmaceutical biotechnology and its applications to health care
is now being realized. Over 30 therapeutic agents produced by the tools of
biotechnology are now available and nearly 300 more are in various stages of
development. Recombinant proteins, monoclonal antibodies, gene therapy, and
vaccines can provide effective treatments and cures for diseases we could only
mitigate in the past. The availability of these drugs presents several
interesting challenges and opportunities to pharmacists. The expense, complexity,
and unique properties of biotechnology agents will continue to alter not only the
knowledge base of pharmacy but also the way pharmacists perform their
professional responsibilities.
PMID- 10185235
TI - Designer drugs: the evolving science of drug discovery.
AB - Drug discovery and design are fundamental to drug development. Until recently,
most drugs were discovered through random screening or developed through
molecular modification. New technologies are revolutionizing this phase of drug
development. Rational drug design, using powerful computers and computational
chemistry and employing X-ray crystallography, nuclear magnetic resonance
spectroscopy, and three-dimensional quantitative structure activity relationship
analysis, is creating highly specific, biologically active molecules by virtual
reality modeling. Sophisticated screening technologies are eliminating all but
the most active lead compounds. These new technologies promise more efficacious,
safe, and cost-effective medications, while minimizing drug development time and
maximizing profits.
PMID- 10185236
TI - The pharmacoeconomics of high-cost biotechnology products.
AB - Biotechnology products have created therapy options in areas that have been
historically limited. These improvements in patient care have resulted in a
reappraisal of the emphasis placed on product acquisition costs and a movement
toward evaluating the impact of the product on the entire health care system.
Strategic planning for biotechnology products allows pharmacists to partner with
the medical staff and financial/administrative representatives of the institution
to measure clinical outcomes, estimate cost and revenue impact, document
utilization, and promote cost-effective use of these new therapies to generate
the maximum benefit for dollars expended.
PMID- 10185237
TI - Reengineering the retail/ambulatory pharmacy for provision of biotechnology
pharmaceutical services.
AB - Biotechnology products offer both problems and opportunities for pharmacists. On
one hand, they are expensive to purchase and keep on inventory. Typical
compensation for outpatient prescriptions does not offset the cost of maintaining
the inventory, or providing the education and training that patients often need
to use biotechnology products properly. On the other hand, there are issues
related to proper storage, preparation, and administration for which pharmacists
are well prepared to address. Pharmacists are also convenient, trusted, and
provide service at relatively low cost. Examples of special services that
pharmacists can provide to improve the use of biotechnology products include
patient education, injection clinics, provision of medical supplies, and
predrawing syringes for patients. Patients are often sent to many providers for
these services, resulting in inconvenience and fragmentation of care. If new
compensation methods can be established to support more comprehensive pharmacy
services, the use of biotechnology products by patients will improve.
PMID- 10185238
TI - Pharmacy alternative futures.
PMID- 10185239
TI - Developing and implementing oral 5-HT3 receptor antagonist guidelines: a
multidisciplinary process.
PMID- 10185240
TI - Lessons learned in managed care.
AB - Competition, reduction in health care premiums, rising health care costs, aging
of the population, and technologic advances are several factors that create both
challenges and opportunities for managed care organizations (MCOs). The demands
to constantly improve quality of care and efficiency of operation while holding
down costs are drivers meant to stimulate organizations to constantly strive to
rethink their process of care provision. The most cost-effective program is one
that maintains its health plan members who are active in the community and away
from the institutional setting. This is optimally achieved through an accessible
and comprehensive ambulatory practice. Innovation and paradigms of practice
change in the acute, subacute, and long-term care arenas have allowed us to
dramatically impact quality and utilization in these expensive areas, while at
the same time freeing up additional time for MCO primary care practitioners to
focus on their community-based patients. MCO primary care providers have not only
supported but welcomed these changes in their organization, recognizing that
these innovations represent a component of the continuum of health care needed to
effectively serve their patients.
PMID- 10185241
TI - Improving warfarin anticoagulation therapy in a community health system.
AB - An internal chart review of warfarin patients revealed a 44 percent complication
rate resulting in higher treatment costs, and identified patient noncompliance,
access to monitoring, and insufficient patient education as contributing factors.
A warfarin usage guideline was created to assist physicians with warfarin
management and subsequently the Anticoagulation Center (ACC) was established. To
date over 950 patients have been managed through the ACC with therapeutic
international normalized ratios an average of 82 percent of the time. Fewer
bleeds and treatment failures have occurred in the ACC group, and a patient
satisfaction survey revealed that ACC patients were very satisfied with their
care more often than non-ACC patients.
PMID- 10185242
TI - Anticoagulation Clinic in the VA Pittsburgh Healthcare System.
AB - This article describes the Anticoagulation Clinic (ACC) within the Veterans
Administration Healthcare System. The clinic has been in operation for 10 years
and has increased patient visits by 550 percent over this time period. Unlike
many ACCs, inpatient anticoagulation management services have lagged behind
outpatient services. The typical patient is an older white male who is prescribed
warfarin for a cardiac condition (atrial fibrillation, mechanical heart valve
replacement, congestive heart failure/cardiomyopathy). The VA system provides
prescriptive authority and offers much latitude for patient management by ACC
pharmacists. A comprehensive credentialing process has been developed, and
quality improvement monitors show warfarin-related complications are comparable
to other clinics and are less than routine medical care. In general, patients are
satisfied with the care they receive and are comfortable with pharmacists
monitoring and adjusting their warfarin therapy.
PMID- 10185243
TI - Clinical pharmacy anticoagulation services in a group model health maintenance
organization.
AB - The clinical pharmacy anticoagulation service (CPAS) at a large group model
health maintenance organization is described. The service has expanded
dramatically from a local service providing anticoagulation monitoring for the
patients of a single physician to a regional service staffed by seven full-time
employees who monitor over 3,000 patients. The structure and operations of the
CPAS are described as well as the processes used to manage anticoagulation
therapy complications. A program for treating patients with deep vein thrombosis
in the outpatient setting using enoxaparin is also described.
PMID- 10185244
TI - Quality assessment and improvement in a university-based anticoagulation
management service.
AB - The quality improvement process in a university-based anticoagulation management
service is described. A clinic overview describes the reporting structure,
patient population, clinic operations, and patient care processes. Quality
improvement is an inherent component to any patient care process. The
Anticoagulation Clinic is addressing improvements by implementing point-of-care
testing, adjusting the full-time equivalent mix, developing a credentialing
process for anticoagulation practitioners, and creating a new consult form. By
obtaining a new computer tracking program, improved clinical outcome tracking
(i.e., thromboembolic and hemorrhagic rates) will occur. Enhancing the format of
patient education and additional patient and physician satisfaction surveys are
components of educational and psychological outcome improvements.
PMID- 10185245
TI - Evolution of collaborative ambulatory anticoagulation consultation services in a
family practice residency.
PMID- 10185246
TI - Unique collaboration targets delays: learn from the impressive results of 31 EDs.
PMID- 10185247
TI - Common problems plaguing IHI (Institute for Healthcare Improvement) participants.
PMID- 10185248
TI - Cutting edge: the ambulatory hospital.
PMID- 10185249
TI - Imaging operations: assessing the radiologist component. Taking professional
inventory.
PMID- 10185250
TI - Performance management.
PMID- 10185251
TI - In vivo MR imaging of brain behavior.
PMID- 10185252
TI - Understanding the motivators in others.
PMID- 10185253
TI - Palliation of bone pain in cancer patients.
PMID- 10185254
TI - The heat is on: time to get cooking.
PMID- 10185255
TI - Critique vs criticism.
AB - Critique can have as much benefit for management as it does for staff members.
The fact is every time you have an opportunity to teach, you gain staying abreast
of your field. Each time someone learns by your instruction, you earn their
respect. Each time you have an opportunity to talk with your staff, you have
first-hand experience of what's going on under your auspice. And each time you
contribute to your staff, you invest in your own success, both personally and
professionally.
PMID- 10185256
TI - Five minutes with Howard Bedlin. Interview by Elise Nakhnikian.
PMID- 10185257
TI - Avoiding RUG burn. Time MDS (minimum data set) assessments right to collect
proper payment.
PMID- 10185258
TI - Senior housing. Learning from the ones that got away.
PMID- 10185259
TI - Subacute strategies. Therapists battle for breathing room.
PMID- 10185260
TI - Lock out crime. How to keep an employee's past from haunting you.
PMID- 10185261
TI - Progress in patient care.
PMID- 10185262
TI - Let them eat cake. To get residents to eat what they need, give them what they
want.
PMID- 10185263
TI - Supervisors or employees? The right of charge nurses to unionize moves to the
courts.
PMID- 10185264
TI - How to spell relief. New guidelines are the first to address elderly's pain.
PMID- 10185265
TI - Five minutes with Joan Schleue-Warden. Interview by Elise Nakhnikian.
PMID- 10185266
TI - Activity-based management: a program for profitability.
PMID- 10185267
TI - Assisted living. Don't overlook the real Alzheimer's market.
PMID- 10185268
TI - Caught short by HCFA's restraining orders.
PMID- 10185269
TI - Assisted living. Get ready for consolidation.
PMID- 10185270
TI - Assisted living. State regulation update.
PMID- 10185271
TI - Assisted living. New players join the game.
PMID- 10185272
TI - Assisted living. Moving into new markets.
PMID- 10185273
TI - Redefining long-term care. Assisted living has caught on fast as an adjunct--or
an alternative--to nursing homes.
PMID- 10185274
TI - 1998 awards. Order of Excellence--best of the best.
PMID- 10185275
TI - Can time heal all wounds?
PMID- 10185276
TI - Policies for policing private duty personnel.
PMID- 10185277
TI - Outsourcing ins and outs. Making it work requires a lot of advance planning.
PMID- 10185278
TI - Five minutes with Steve Moses. Interview by Yvonne Parsons.
PMID- 10185279
TI - Managed care. A proliferation of players.
PMID- 10185280
TI - CCRCs shine in the shadows. Communities hold their own against assisted living.
PMID- 10185282
TI - Make 'em laugh. Humor programs can help residents heal--seriously.
PMID- 10185281
TI - Subacute strategies. Get away from your desk and onto the floor.
PMID- 10185283
TI - Decoding dementia.
PMID- 10185284
TI - Flatliners. Survey finds administrators' pay on a par with last year's.
PMID- 10185285
TI - Rewriting the rules. Ten steps to avoiding sexual harassment liability.
PMID- 10185286
TI - Error? What error? Report, don't rationalize, your medication mistakes.
PMID- 10185287
TI - Reinventing REITs. Is diversification inevitable--or even desirable?
PMID- 10185288
TI - Food-drug interactions. Unsolved mysteries and savvy solutions.
PMID- 10185289
TI - Training future chefs at Opryland.
AB - Dina Starks is the culinary apprentice coordinator at Opryland Hotel Convention
Center in Nashville, Tenn. Her apprentices have the unique opportunity to
practice the culinary arts at the largest hotel convention center in the world,
in a setting that has 15 restaurants and nearly 3,000 rooms.
PMID- 10185290
TI - ADRs--problem or opportunity?
PMID- 10185291
TI - Incentives can strengthen the team. They don't have to be expensive.
PMID- 10185292
TI - Expanding your scope. Opportunities in the commercial food industry.
PMID- 10185294
TI - Food safety on the Internet.
PMID- 10185293
TI - The long-term care survey process.
PMID- 10185295
TI - Conducting an Internet search. Proper use of Boolean Syntax saves time.
PMID- 10185296
TI - Perpetual preparedness. Consistent high quality is today's goal.
PMID- 10185298
TI - Tips for improving patient education.
PMID- 10185297
TI - Prealbumin for screening and assessment. A quick, efficient, and reliable tool.
AB - Pat Sutor is a registered dietitian at Elmhurst Memorial Hospital in Elmhurst,
Ill. At this hospital, prealbumin values are used for initial screening and
follow-up to help determine the nutritional status of patients. She describes how
this method has been found to be effective for directing the daily activities of
dietitians and for quantifying the outcomes of nutrition intervention for
physicians.
PMID- 10185299
TI - Selecting materials for patient education. 15 innovative strategies.
PMID- 10185300
TI - Lessons from the pros. Tips from award winners who stay ahead of their
competition.
PMID- 10185301
TI - A vision of excellence. Part 1 in a series on food service excellence.
PMID- 10185302
TI - The "take a nurse to lunch" program. A unique focus group improves and promotes
food services.
AB - Dan Booth is the director of hospitality services for MaineGeneral Health. For
this 450-bed health care organization, he directs six departments, which include
environmental services, food and nutrition, security, laundry services,
telecommunications, and transportation. In this article he describes how his Take
a Nurse to Lunch program operates, what its benefits are, and how it was
implemented.
PMID- 10185303
TI - Market research techniques. How three large chains learn what their customers
want.
PMID- 10185304
TI - If you can't beat 'em.... insurers and brokers are cashing in on grassroots
reform.
PMID- 10185305
TI - Relationships building. Measure service quality across health care encounters.
AB - The relationships between service quality and satisfaction is a function of
multiple service encounters across a wide variety of exchange partners within a
health care organization. Studying the patient provider relationship leads to
improved service quality. The authors report their findings from a study that
tests a relationship-building framework that integrates service quality issues
across multiple internal health care publics. Strategies for developing a strong
patient-provider relationship bond are also discussed.
PMID- 10185306
TI - Out of plan. Certain HMO characteristics affect physicians' satisfaction and
influence their decision to reenroll.
AB - The authors examine the issue of continuity, which is directly associated with
patient satisfaction, from the perspective of the physician. They attempt to
determine which factors are most important in determining physician satisfaction
with an HMO and the link between satisfaction with an HMO and intent to remain
affiliated with that HMO. Their study reveals that 11 factors explain 71% of the
variation in overall physician satisfaction and that a physician's satisfaction
with a plan is closely linked to intentions to reenroll. Implications for HMOs,
physicians, employers, and public policy makers are explored.
PMID- 10185307
TI - Managing emotions. Accenting the positive might not produce the highest
satisfaction payoff.
AB - The relationship between patient emotions during hospitalization and their
retrospective satisfaction varies across service elements, across emotions, and
is influenced by the temporal positioning of both emotions and the service
element. Marketers should concentrate on reducing negative emotions attributed to
the provider (e.g., hostility and frustration) and to the hospitalization
situation (e.g., distress and depression), according to the results of the
authors' study. Providers also should attempt to alleviate negative emotional
states connected with arousal (e.g., jittery and excited). Positive emotions were
found to be only weakly related to satisfaction. The authors suggest segmenting
patients on the basis of their emotional states at particular junctures of the
service delivery and then "socializing" both providers and patients to ensure
successful emotion management.
PMID- 10185308
TI - Satisfaction by design. 'Place' component of the marketing mix takes center stage
for some providers.
PMID- 10185309
TI - Better marketing through a principles-based model.
PMID- 10185310
TI - Current challenges to providing personalized care in a long term care facility.
AB - Long term care facilities are finding it increasingly difficult to deliver
quality, personalized care to their clients. This is related to: the integration
of frail, elderly residents with cognitive impairment and/or behavioural
disorders; ethical dilemmas; settings that are not conducive to providing a
stimulating and supportive atmosphere which would enhance care delivery;
admission of residents with increasingly complex care needs without adequate
funding and/or support services, and staff training needs. This paper defines how
one organization intends to facilitate the changes required to improve the
delivery of quality, personalized care.
PMID- 10185311
TI - Elder abuse and one community's response.
AB - Elder abuse has come to be recognized as any act of both commission or omission
that causes harm or loss to elderly people. This can include active or passive
neglect, violence, sexual or emotional abuse, various kinds of theft, and
deprivation of the person's human rights. Elder abuse has many causes. The
Hastings and Prince Edward Council on Aging developed an Elder Abuse Community
Response Protocol to help address this problem.
PMID- 10185312
TI - A study of 131 patients with schizophrenia and provision for them.
AB - One hundred and thirty-one patients came to the Institute of Biological
Psychiatry at Bangor, accompanied by 161 healthy blood relatives, spouses and
friends. A history was taken and a diagnosis of schizophrenia was made using DSM
IIIR criteria. The patients were examined to see if they had any concurrent
physical disease. Venous blood samples were taken for measurements of chemical
constituents believed to be involved in schizophrenia. The population of patients
is described, and the views of the patients and their relatives were noted.
Recommendations are made about how provision for patients might be improved.
PMID- 10185313
TI - Quality in a service function. Value added?
PMID- 10185314
TI - Preliminary evaluation of the efficacy and implementation of the new NHS
complaints procedure.
AB - The increase (28.8 per cent) in the number of complaints from pre-New NHS
Complaints Procedure to the implementation of the new procedures in 1996 is a
matter of concern because it is estimated that the current figure represents only
40 per cent of the number of people with some dissatisfaction. The Wilson Report
prompted Government initiatives in producing a new NHS Complaints Procedure. The
new procedure allows for complaints to be dealt with at a local level, or in a
minority of cases through Independent Review. The new procedures, which were
introduced in April 1996, oblige Trusts, GP practices and Health Boards to
establish a Written Local Resolution process for handling complaints,
responsibility for implementation lying with individual trusts. A preliminary
assessment of the New Procedures was carried out in Lothian. A qualitative
approach was utilised and semi-structured taped interviews lasting on average one
hour ten minutes were administered to the six complaints officers. This study
concentrates on how the six Lothian NHS Trusts are implementing the new
procedure, the openness in complaints handling, and the awareness of how
complaints can be used to improve standards. The conclusion is that Local
Resolution 1 has been successful, and that complaints do receive a speedy
response. The process is much simpler and easier for the lay population to
access. Reservations remain, however, towards the Independent Review procedure.
PMID- 10185315
TI - Health care utilization by the elderly in HMOs: comparing risk and cost
contracts.
AB - Data are utilized collected from the American Association of Health Plans, a
trade association representing HMOs, to study differences in utilization patterns
between medicare beneficiaries enrolled in Medicare risk and cost contracts with
health plans. Utilization is measured by the number of ambulatory procedures
performed, outpatient and emergency room visits, and acute and nonacute
discharges. Compared to elders enrolled in risk plans, those in cost arrangements
appear to exhibit higher inpatient and outpatient use. Members of for-profit
plans experienced greater outpatient visits, accreditation did not appear to
influence utilization, and IPA arrangements resulted in a decrease in outpatient
utilization. Financial and policy issues are discussed.
PMID- 10185317
TI - What is adequate health care and how can quality of care be improved?
AB - Attempts to improve patient care, its increasing cost and the aggressive
malpractice environment have highlighted the need for standards of professional
accountability. However, current measures of quality of care have mostly been met
with skepticism by the medical community. These measures have been criticized for
their uncertain validity and for focusing on secondary aspects of service that
measure what is minimally acceptable. The objective of this essay is to review
quality improvement methods that have been reported to be feasible, effective and
acceptable by practicing physicians. The successful implementation of these
methods seems to be related to their being nonintrusive, nonthreatening, and
based on agreed upon standards of care. We believe that these three features are
essential for a continuous quality improvement process in health care.
PMID- 10185316
TI - The development of a quality model: measuring effective midwifery services
(MEMS).
AB - In a wider debate on defining and measuring quality in health care, there is a
particular need for frameworks for understanding and managing quality in specific
specialties. This article addresses the definition and measurement of quality in
maternity care. It develops a pro forma for monitoring and hence managing
midwifery quality.
PMID- 10185318
TI - Quality systems in health care: a situational approach.
AB - Many views on quality management in professional service firms derived from ideas
of industrial quality management. It seems that in the area of professional
services these ideas are taken over without much criticism. For instance, the
ideas on quality control and quality assurance generally are heavily based on the
ISO 9000 standards. In The Netherlands the PACE-standards have been deduced from
the ISO 9000 standards for application in hospitals. In this paper it has been
argued that in many cases a more situational approach will be preferable. A
global framework for a quality system in a professional service firm has been
presented. This framework has been compared with the restrictions for quality
systems in hospitals, following from the PACE-standards.
PMID- 10185319
TI - Re-engineering.
PMID- 10185320
TI - Quality of care and patient satisfaction in budget-holding clinics.
AB - A budget-holding program was implemented in nine primary care clinics in the
Negev district of Kupat Holim Clinic, Israel's largest sick fund. This study,
carried out from 1991 to 1994, evaluates the impact of this program on patient
satisfaction and other selected indicators of quality of care, using a controlled
case study methodology. Structured questionnaires were used in face-to-face
interviews with a representative stratified sample of 523 patients registered in
the clinics. Patient reports were used to measure patient satisfaction,
accessibility of services, comprehensiveness of care, responsiveness to patients'
needs and performance of preventive medicine activities. Other research tools
included staff surveys, in-depth interviews and administrative data on transfer
among sick funds. The findings counter fears that budgetary control and cost
containment negatively affect quality of care and patient satisfaction. However,
the program did not fulfill expectations regarding improvement in clinic services
and patient satisfaction.
PMID- 10185321
TI - Quality assessment of discharge letters in a French university hospital.
AB - The quality of discharge letters has been evaluated in order to initiate a
process of improved communications between the hospital and general
practitioners. From each of 37 volunteer clinical departments of the hospital, a
random sample of 30 stays was selected among the hospitalisations for one year.
The quality of discharge letters was assessed according to recipients' needs and
to French legislation. In total, 1,024 medical records were relevant and were
analysed. This study showed deficiencies in management of discharge letters in
the hospital. It constitutes the first step of a quality improvement process
based on the awareness of concerned actors through information feedback and the
follow-up of specific indicators.
PMID- 10185322
TI - Service-level agreements at the Huddersfield NHS Trust.
AB - Service-level agreements (SLAs) have been claimed to be an excellent vehicle for
organisational improvement where there is a substantial degree of departmental
autonomy. Such a situation is likely to exist in NHS trust hospitals because of
the differentiated nature of the work performed by each department, with varying
degrees of specialisation and professionalism, access to patients, use of
technology and differing cost bases but also an interdependence of the direct
services to the support services. It is proposed that SLAs can be used to promote
improved integration between departments, quality assurance and provide a
framework for cost transfer charging. The article describes and analyses SLAs
from an overview of the idea to the particular implementation to date at the
Huddersfield NHS Trust. SLAs have been negotiated between the Directorate of
Clinical Support and its customers, and these are supported by computerised
measurement and reporting tools.
PMID- 10185323
TI - Process analysis in general practice--a new perspective?
AB - This paper reports the initial findings from a study of the application of
process analysis into a general practice. It discusses the issues surrounding the
relationships between clinical and managerial tasks. A new model of primary care
is proposed which takes into account management issues and separates out non
patient contact activities. Evidence is presented and conclusions and drawn about
front/back office activities, general practice as a small business, patient care
and suggestions are made for future work.
PMID- 10185324
TI - Block appointments in an overloaded South African health centre: quantitative and
qualitative evaluation.
AB - Long waiting times are a serious problem for patients using urban health centres
in developing countries. A block appointment system was introduced and evaluated
in a large South African health centre. Waiting times of all patients were
measured over a one-week period before and after the implementation of
appointments. Focus group and individual interviews were conducted with staff and
patients. After introducing appointments, patients with acute and chronic
illnesses and having appointments had significantly shorter waits than similar
patients without appointments (difference in median waits: 63 and 39 minutes
respectively). Appointments had no benefits for patients not seeing doctors or
collecting repeat medication. There was, however, an overall increase in
patients' waiting times after introducing the system, mainly due to one atypical
day in the follow-up study. Focus groups and interviews revealed that staff were
sceptical at baseline but at follow-up were positive about the system. Patients
were enthusiastic about the appointment system at all stages. The study shows
that block appointments can reduce patient waiting times for acute patients, but
may not be suitable for all patients. Staff and patients had different views,
which converged with experience of the new system.
PMID- 10185325
TI - Comparing public and private hospital care service quality.
AB - The study applies the principles behind the SERVQUAL model and uses Donabedian's
framework to compare and contrast Malta's public and private hospital care
service quality. Through the identification of 16 service quality indicators and
the use of a Likert-type scale, two questionnaires were developed. The first
questionnaire measured patient pre-admission expectations for public and private
hospital service quality (in respect of one another). It also determined the
weighted importance given to the different service quality indicators. The second
questionnaire measured patient perceptions of provided service quality. Results
showed that private hospitals are expected to offer a higher quality service,
particularly in the "hotel services", but it was the public sector that was
exceeding its patients' expectations by the wider margin. A number of
implications for public and private hospital management and policy makers were
identified.
PMID- 10185326
TI - Southampton University Hospitals NHS Trust: our approach to performance
management.
AB - Southampton University Hospitals Trust has developed a performance management
strategy which is improving service quality, overcoming interdepartmental
blockages and delivering significant savings with greater departmental ownership
and commitment. The strategy also offers a solution to the age-old problem of if
and when to market test by doing this only when it is apparent the inhouse team
cannot deliver the required level of performance. This is achieved by agreeing
the initiating key targets to reach or improve on high levels of performance
using a variety of techniques including benchmarking, value management and
external technical advice.
PMID- 10185327
TI - Accountability and quality in managed care: implications for health care
practitioners.
AB - The development of managed care plans is the most dramatic change in the USA's
health care system in recent decades. Despite the widespread growth, society is
increasingly concerned with the quality of managed care programs. This article
addresses the regulatory pressures that are being placed on managed care
organisations and examines what health care practitioners can do to minimize the
impact of increased regulation. We look at the major factors that are likely to
bring about changes in the health care sector, and predict how these changes will
affect the quality of health care that is being delivered in the near future.
Addresses how quality can become and remain the primary factor in the delivery of
health care services. Finally, concludes that greater involvement by the federal
government is necessary to protect consumers' rights, and ensure better quality
health care from managed care programs.
PMID- 10185328
TI - Consumer responses to health care: women and maternity services.
AB - The importance of understanding consumer perceptions of services is widely
acknowledged. This is becoming more relevant in health care, as attempts to
incorporate users' views into service development and evaluation are increasing.
This study focused on women's responses to their recent experience of maternity
care, and sought to gain insight into the service features they associated with
negative and positive reactions. Postal questionnaires were sent to antenatal and
postnatal women. Two open questions invited women to note if any aspects of their
care had particularly impressed or bothered them. There was variation in the
factors identified through the different phases of the service--antenatal, labour
and postnatal care. However, staff attitudes were a main source of positive
comments throughout the service, and lack of information and poor explanations
were a consistent source of negative responses. Providing consumers with an
opportunity to give feedback on their service experience should be based on
issues which are relevant to them, not just on those which are measurable.
PMID- 10185329
TI - The outpatient experience: results of a patient feedback survey.
AB - Patient surveys can be used to enable hospital management to evaluate the
services they provide. This study shows high levels of patient satisfaction with
the quality of their consultations and the attitude shown to them by medical
staff. Patient feedback shows that despite the introduction of the Patients'
Charter, waiting times from referral to appointment and delays in clinics are
still identified as the main areas for improvement. Findings show that patients
are, however, remarkably tolerant and understanding of the pressures and demands
placed upon outpatient staff.
PMID- 10185330
TI - An innovative method of government surveillance of services for the aged in
Israel.
AB - Explains the conceptual framework behind and the foundation and implementation of
the regulation, assessment, follow-up (RAF) method, and continuous improvement of
quality of care in the Israeli Government surveillance of long-term care
institutions. The RAF method has made crucial changes in the goals, tasks and
tools of surveillance and in therapeutic approaches to the elderly. The
"maintenance approach" has been replaced by a "rehabilitative approach" bringing
about a real improvement in the quality of care in institutions. Presents
selected findings from an evaluation of the RAF method's use in the surveillance
system operated by the Israeli Service for The Aged of the Ministry of Labor and
Social Affairs.
PMID- 10185331
TI - Practices of the best companies in the medical industry.
AB - A report containing information about three of the top medical manufacturing
companies in the world--Baxter Healthcare Corporation, Johnson & Johnson and
Medtronic, Inc. Resources have been gathered and employees in key positions from
each company have been interviewed to obtain the most current and accurate
information. Interviewees were asked what factors contribute to their company's
success. These factors were then explored more explicitly through a variety of
publications, and the results are included in this report. In today's competitive
market, companies must keep current with the market trends and be flexible and
open to changing and/or improving their practices in order to remain successful.
It has been found that although the main focuses of each company may be similar,
the processes by which they strive to meet their goals are quite unique.
PMID- 10185332
TI - Integrated health systems: they will set benchmarks for performance.
AB - Nearly 600 health care delivery systems are in the process of integrating, and
the number of highly integrated health systems based in rural areas jumped 72% in
1997. The primary reason for the integration trend is diminishing resources
brought on by restricted reimbursement. Experts agree it will be difficult for
freestanding hospitals to survive.
PMID- 10185333
TI - 10 keys to successful integrated systems.
PMID- 10185334
TI - Henry Ford achieves smooth integration.
AB - Henry Ford saw the value of vertical integration early in the automobile industry
and applied it to health care as well when he founded a hospital in 1915 that
eventually would anchor the Henry Ford Health System. Provider components include
hospitals, home health agencies, nursing homes, a managed care plan, physician
practices, and freestanding outpatient surgery centers. Strong governance and
information systems are key to successful integration.
PMID- 10185336
TI - How to get your best practices on the Web.
AB - The Best Practice Network, founded by 13 nursing organizations, is a forum for
sharing information among health care professionals. One of the network's main
projects has been the development of a Web site offering free, easy access to
best practice ideas. The Web site offers tips on everyday innovations, discussion
groups, and a place to post best practice ideas.
PMID- 10185335
TI - Best practices net big food service savings.
AB - A computerized, handheld menu entry system means lower costs and higher patient
satisfaction for three hospitals. Personal touch, less waste, and more efficiency
results from spoken bedside menus. System automatically tracks changes in rooms
and patient diet.
PMID- 10185337
TI - Performance citation award 1998--a well-deserved award.
PMID- 10185338
TI - The health care ministry in the new millennium: are Christian values possible?
PMID- 10185339
TI - It takes a whole person to bring healing.
PMID- 10185340
TI - Towards a focus on the sick and dying.
PMID- 10185341
TI - Radiology project delivers 16% cut in costs per exam.
PMID- 10185342
TI - Remote radiology viewing speeds report time, reduces transfers and
hospitalizations.
PMID- 10185343
TI - Reduce the medical, economic impact of preterm delivery.
AB - Reducing hospitalization for threatened preterm labor: A new laboratory test for
preterm labor helps determine which women are unlikely to deliver soon, avoiding
unnecessary hospital stays. A clinical study conducted at a New Mexico hospital
shows the test saved $486,000 in a 12-month period.
PMID- 10185344
TI - Outreach program slashes Florida health network's rate of cesarean sections.
PMID- 10185345
TI - Antibiotic-laced urinary catheter helps prevent costly infections.
AB - Treating urinary tract infections at the source: Urinary tract infection is a
common problem in hospitals, particularly among patients who require long-term
management with indwelling urinary catheters. A new Foley catheter, made of
silicon imbedded with a broad-spectrum antibiotic, shows a 10-fold reduction in
UTI within three days of use. Its maker claims hospitals can save $68,000 to
$438,000 per 1,000 catheters.
PMID- 10185346
TI - Hospitals tap water conservation measures to keep up with rising costs.
AB - Water shortage? With water rates rising at a double-digit pace, an increasing
number of hospitals and health systems are turning to high-tech devices to
conserve water resources. One Boston engineering firm guarantees health care
clients a savings of 20% to 40%.
PMID- 10185347
TI - Evaluate cost-benefits of new anti-emesis drug.
AB - Chemotherapy side effects: A new category of drug offers relief of nausea and
vomiting for about half of patients undergoing chemotherapy. And while the new
drug is costly, its use can eliminate other expenses associated with chemo side
effects while helping patients feel a whole lot better during treatment.
PMID- 10185348
TI - Providers gear up to walk a mile in insurer's shoes.
PMID- 10185349
TI - Medicare 'mega reg' offers providers mixed bag.
AB - Although the Medicare+Choice regs mostly cover how plans will operate, they also
include provisions that will directly, and indirectly, affect Medicare risk
providers. Find out how some of these rules might impact you.
PMID- 10185350
TI - Can hybrid Medicare plan solve utilization woes?
AB - Reducing inpatient hospitalizations as a way to control senior members' costs
causes outpatient utilization to rise. The answer may lie in creating a hybrid
Medicare plan that combines managed care with medical savings accounts. Learn
more about the kinds of plans that may exist in the future.
PMID- 10185351
TI - Colorado providers prove safety net's place in Medicaid risk.
AB - At least one system in Denver is proof that safety net providers can succeed in
Medicaid risk. Find out how one provider and its partners went from fearing
managed care to specializing in it.
PMID- 10185352
TI - Senior-age population growth may redefine 'frail elderly'.
AB - Data File: A key to future success in Medicare risk may be how well you manage
your frail elderly members who have multiple health problems and chronic
conditions. While they may just be a handful of patients in your panel now, data
from the U.S. Census Bureau show their numbers are growing.
PMID- 10185353
TI - Survey reveals utilization of special needs kids.
AB - Are you ready to care for special needs children? As states expand their managed
Medicaid programs to include previously uninsured children, providers will be
seeing more kids with specials needs. Find out what families of these children
need and expect from their health care plans and providers from a recent survey.
PMID- 10185354
TI - Perspectives. Big gaps outweigh small gains in struggle for better Indian health.
PMID- 10185355
TI - Marketplace. U.S. health care exports threatened, warns report asking for policy
changes.
PMID- 10185356
TI - Perspectives. Beyond the managed care debate: initiatives mount to tackle health
system's quality gaps and 'hidden epidemic' of error.
PMID- 10185358
TI - A slightly softer touch for hospital compliance plans.
PMID- 10185357
TI - Hospitals feel taxed by Clinton budget.
PMID- 10185359
TI - At the eye of the storm. HCFA's Kathleen Buto talks about an era of change.
PMID- 10185360
TI - Making a federal case of managed care.
PMID- 10185361
TI - Life after deregulation.
PMID- 10185362
TI - Volume and value? The Stark II regulations are weighty to be sure, but will they
help or hinder the health system?
PMID- 10185363
TI - HCFA regs turn home health upside down.
PMID- 10185364
TI - HCFA offers first look at transfer policy, wage index.
PMID- 10185365
TI - FAHS refers Stark II reactions to HCFA.
PMID- 10185366
TI - Skilled nursing facility PPS rules released.
PMID- 10185367
TI - Shift to outpatient services spurs rapid growth in ambulatory surgery centers.
PMID- 10185368
TI - "Protection" plans may be no such thing.
PMID- 10185369
TI - Utilities and preferences for health states: time for a pragmatic approach?
PMID- 10185370
TI - Why, when and how should patients be charged?
PMID- 10185371
TI - Expert panel assessment of appropriateness of abdominal aortic aneurysm surgery:
global judgement versus probability estimation.
AB - OBJECTIVE: To compare an expert panel's global assessment of appropriateness of
elective surgery for abdominal aortic aneurysms (AAA) with their assessment of
the effect of surgery on the probability of 5-year mortality. METHODS: Nine
expert panel members rated the appropriateness of 120 scenarios for elective AAA
repair on a nine-point scale, and also estimated the 5-year probability of AAA
related death and of non-AAA related death among 30-day survivors of AAA surgery
and among patients with unoperated AAA. These probabilities were used to
determine differences in 5-year probability of mortality of surgery vs. no
surgery for each scenario. Three categories of appropriateness were defined based
on these differences: inappropriate (< 0%), equivocal (0-5%), and appropriate (>
5%). RESULTS: The distribution of scenarios was inappropriate (39%), equivocal
(12%), and appropriate (49%) based on probability estimates and inappropriate
(43%), equivocal (22%), and appropriate (36%) based on global assessment. There
was poor agreement between the two methods, with a Kappa coefficient = 0.28 (95%
CI: 0.23 to 0.32). Although a higher proportion of scenarios were rated as
appropriate using probability estimation rather than global judgment, the level
of agreement among members of the panel was similar, Kappa coefficient = 0.07
(95% CI: -0.07 to 0.72). CONCLUSIONS: Experts disagree about the appropriate
indications for elective surgery for AAA. Explicit estimates used in a decision
analysis may provide a better assessment of appropriate indications than the
global judgment of experts. Global assessment of the appropriateness of AAA
surgery based on panel members' review of research evidence for increased
survival appears to include implicitly their valuation of outcomes.
PMID- 10185373
TI - Day case surgery trends in England: the influences of target setting and of
general practitioner fundholding.
AB - OBJECTIVES: To describe the trends in the proportion of elective surgery carried
out as day cases, and the impact of the setting of targets and the introduction
of general practitioner (GP) fundholding on the use of day surgery. METHODS:
Cross-sectional analysis of Hospital Episode Statistics for England. 1990/1991 to
1994/1995, comparing procedures for which targets were and were not set, and
comparing types of purchaser (GP fundholder and health authority). RESULTS:
Elective surgical procedures increased from 2.7 million in 1990/1991 to 3.9
million in 1994/1995, a 44% increase. Increased numbers of day cases (up 117%)
accounted for almost all of the increased total activity. The proportion of day
cases rose from 35% to 53% over the period. Those procedures for which targets
were set (over 25% of elective surgery) had a slightly lower day case proportion
in 1990/1991 (34% compared to 36%) but slightly higher by 1994/1995 (57% compared
to 52%). GP fundholders generally had slightly lower proportions treated as day
cases compared to health authorities. CONCLUSIONS: Day cases were additional to,
rather than a substitute for, inpatient treatments. Setting day case targets may
have been associated with growth in use of day surgery, but there was no
association with type of purchaser.
PMID- 10185374
TI - Variations in use of cardiac services in England: perceptions of general
practitioners, general physicians and cardiologists.
AB - OBJECTIVE: To explain why those who live some distance from tertiary cardiac
centres make less use of coronary angiography and revascularisation than those
who live close by, and why people living in particular wards within certain
districts make less use of services than might be expected from their level of
need. METHOD: Semi-structured interviews with 24 general practitioners (GPs) in
two English health districts (Morecambe Bay and East Lancashire), five general
physicians working in district general hospitals, and four interventional
cardiologists working in tertiary centres. Transcripts of audiotape recordings
were analysed using the constant comparative method. RESULTS: Those living far
from tertiary centres are usually referred to general physicians before they are
referred for angiography. The general physicians tend to be more conservative in
their approach to treatment than interventional cardiologists. GPs working near
tertiary centres are able to refer directly to interventional cardiologists.
There are also logistical and economic reasons for inequitable use of services.
Some GPs perceived that patients of South Asian descent undergo fewer
investigations than might be expected because of communication or other
difficulties. CONCLUSION: Use of cardiac services would be more equitable if
there were interventional cardiologists based in district general hospitals who
could perform angiograms for their own patients in the tertiary centres. Patients
might also benefit in angiograms could be conducted in selected district general
hospitals. Further qualitative research, involving both doctors and patients, is
needed to explore other reasons for relatively low rates of investigation and
revascularisation in certain groups of patients.
PMID- 10185372
TI - Public, private and voluntary residential mental health care: is there a cost
difference?
AB - OBJECTIVES: To determine how public (NHS or local government), private (for
profit) and voluntary (non-profit) providers of residential mental health care
compare. Do they support different clienteles? And do their services cost
different amounts? METHODS: Based on a cross-sectional survey of residential care
facilities and their residents in eight English and Welsh localities, the
characteristics and costs of care in the different sectors (NHS, local
government, private, voluntary) were compared. Variations in cost were examined
in relation to residents' characteristics using multiple regression analyses,
which also allowed standardisation of results before making inter-sectoral
comparisons. RESULTS: Private and voluntary providers of residential care support
different clienteles from the public sector. The patterns of inter-sectoral cost
differences vary between London and non-London localities. In London, voluntary
sector facilities may be more cost-efficient than the other sectors, but local
government/private sector comparisons show no consistent difference. Outside
London, the results suggest clear cost advantages for the private and voluntary
sectors over the local government sector. CONCLUSIONS: Private and voluntary
providers may have some economic advantages over their public counterparts.
However, outcomes for residents were not studied, leaving unanswered the question
of comparative cost-effectiveness.
PMID- 10185375
TI - Decision analysis in the selection, design and application of clinical and health
services research.
AB - Research evidence will never be sufficient to tell us how treatments compare in
every group or class of patients. It will always be necessary to particularize
from the general to the specific. The ad hoc way this is normally done contrasts
with the rigour of the research process. However, extrapolating from the general
to the particular can be made equally rigorous by Decision Analytic modelling.
Furthermore, research evidence is not enough when decisions turn on multiple
objectives, which must be traded off against each other. Research evidence and
patients' preferences can be reconciled, again rigorously, by using Decision
Analysis to show how probabilities and values interact. In addition, research
should be designed around likely clinical impact, and this in turn can be made
explicit by Decision Analytic modelling. In particular, sample size calculations
should be based on such explicit modelling, rather than current procedures, which
seldom seek to defend the size of clinical effects sought.
PMID- 10185376
TI - Catching goldfish: quality in qualitative research.
AB - This paper reviews the contribution of qualitative methods to health services
research (HSR) and discusses some of the issues involved in recognizing quality
in such work. The place of qualitative work is first defined by reference to
Archie Cochrane's agenda for HSR and the limitations of the recent focus on
randomized trials as the standard method. Health care practice involves large
elements of improvisation which cannot be captured by evidence-based approaches.
Qualitative methods offer ways of understanding this improvisation and of
identifying more efficient and effective practices, as well as considering the
traditional topics of equity and humanity. The methodological procedures of
qualitative work reflect a long-established inductive tradition in scientific
practice. The logic of grounded theory provides a contemporary specification. In
its application, it is quite different from the methodological anarchy of
postmodernism. The use of qualitative research and the theoretically stated
generalizations which arise from it inform reflective work by health service
managers, planners and clinicians.
PMID- 10185377
TI - Managed care: US research evidence and its lessons for the NHS.
AB - OBJECTIVES: To review the high quality US evidence on performance of managed
health care organisations and the available US evidence on specific managed care
techniques; namely, financial incentives, utilisation management and review,
physician profiling and disease management. METHODS: Literature searches were
conducted using numerous databases including Medline, Embase, the Social Sciences
Citation Index and the National Health Service (NHS) Centre for Reviews and
Dissemination library. For inclusion of evaluations of overall performance,
studies had to use a comparison group (typically fee-for-service patients), make
appropriate statistical adjustments for differences between groups, and be
published in a peer-reviewed journal from 1980 forward. For assessments of
techniques, less-demanding inclusion criteria reflected the paucity of
generalisable literature; however, more current results were required (1990
forward). RESULTS: We identified 70 articles for systematic review, covering 18
dimensions of performance (e.g. utilisation, quality of care, consumer
satisfaction, equity). The strength of the evidence varied by dimension. It was
strongest for utilisation and quality. In general, managed care seems to reduce
hospitalisation and use of high-cost discretionary services, to increase
preventive screening, and to be neutral in terms of patient outcomes. As for
specific techniques, we identified 19 articles for review, but limitations of
these studies prevented our drawing any definite conclusions about techniques'
effectiveness. This is an important, if somewhat negative, conclusion.
CONCLUSIONS: Applying US evidence is complicated by an irrelevant comparator and
a higher baseline of utilisation. Managed care brought Americans the familiar NHS
practices of population-based health care and resource management through
gatekeeping; hence, changes due to UK adoption of managed care techniques may be
modest. US evidence should be used to generate hypotheses, not to predict UK
behaviour.
PMID- 10185378
TI - Does volume really affect outcome? Lessons from the evidence.
AB - There is a prevailing consensus that the quality of health services can be
improved by concentrating care in the hands of those providers who carry out
larger volumes of activity. The substantial research literature indicates a
positive volume-quality relationship. However, these conclusions are largely
based on observational studies using administrative databases which are poorly
adjusted for case mix. Better control for confounding shows that volume-quality
effects in several cases may be an artefact. The research is also difficult to
interpret because of the limited measurement of outcomes, poor analysis of the
relative contributions of the clinician and the hospital levels, and the lack of
clarity about the direction of cause and effect. Most research is insufficiently
reliable to inform policy on the use of volume for credentialling or for the re
configuration of services.
PMID- 10185379
TI - Managed care classes make doctors more comfortable.
PMID- 10185380
TI - Taking advantage of Medicare+Choice: where are the opportunities?
PMID- 10185381
TI - Capitation made simple: one IPA's tale of getting doctors to share risk happily.
PMID- 10185382
TI - Tactics from touch to transportation retain Medicare members.
PMID- 10185383
TI - Formulary economics must consider costs beyond direct healthcare.
PMID- 10185384
TI - Migrating users to new applications tougher with Y2K.
PMID- 10185385
TI - Developing a physician-owned plan.
PMID- 10185386
TI - When mergers deadlock, a third party can break through.
PMID- 10185387
TI - Contact capitation eases specialists into risk-sharing.
PMID- 10185388
TI - Health plans are discovering valuable partners in consumers, employers.
PMID- 10185389
TI - Listening to patients' needs leads Mass. hospital to remarkable turnaround.
PMID- 10185390
TI - Improved end-of-life care proves worthwhile, even at higher cost.
PMID- 10185391
TI - Legal strategies are integral to millennium bug planning.
PMID- 10185393
TI - Cultural sensitivity could pave the way to capturing minority populations.
PMID- 10185392
TI - The emergence of alternative medicine.
PMID- 10185394
TI - Getting doctors to give up control brings happier patients, savings.
PMID- 10185395
TI - Working caregivers. A growing market.
AB - By searching for ways to make themselves more valuable, home care agencies often
build bridges to their communities through identifying new services to offer.
Agencies that begin to develop work-family balance programs will find themselves
ahead of the curve. They make themselves invaluable to companies by providing
services that make employees happier and healthier.
PMID- 10185396
TI - Expanding beyond the traditional framework.
AB - Providers need to learn to think "out of the box" if they are going to prosper
during these changing times in health care. In particular, they need to diversify
their product lines to position for the rapidly growing population of elders, as
well as the accompanying informal caregivers.
PMID- 10185397
TI - Establishing private duty in a Medicare world.
AB - The Balanced Budget Act of 1997 projects $16.2 billion in Medicare cuts over five
years, which will force dramatic changes in the home care delivery system.
Medicare agencies with a good public image and strong referral sources are in a
strong market position to offer private-duty services. Agencies in a weak market
position should immediately begin to diversify their services to succeed in this
new environment. Private duty can be lucrative if agency management establishes
efficient systems, maintains high standards, and thinks like entrepreneurs.
PMID- 10185398
TI - Serving amputee patients in rural settings.
AB - Managing care for amputee patients becomes complicated in a rural setting, where
members of the care team are spread out and have overlapping roles. The solution
to this situation is to start communication early in the process of getting a
prosthesis.
PMID- 10185399
TI - Implementing a visual rehabilitation program.
AB - Improving visual skills among home care patients has ramifications across all
disciplines, affecting both their care and quality of life. The home creates an
ideal setting for visual rehabilitation programs. Education and training to
individuals in their own homes fosters enthusiasm. Modifications made in the home
offer long-lasting benefits.
PMID- 10185400
TI - Music therapy and home care.
AB - As home care looks to alternative programs to serve the community and generate
income, one service that is beginning to attract more attention is music therapy.
As a means to relaxation and healing, this therapy can help patients heal from
within and even strengthens the immune system.
PMID- 10185401
TI - Home care business opportunities in Europe.
AB - The demand for home care services will continue to grow exponentially around the
world. This demand is being driven by demographics, technology, and personal
choice. Providers of home care have a great deal to teach and learn from each
other. The opportunities for collaboration and joint ventures are great now and
will continue to increase with the passing of time. This article has been
extracted from a 1996 panel discussion at the International Home Care Forum held
in Nashville, Tennessee.
PMID- 10185402
TI - Eight essential steps for effective data collection and use.
AB - Home care providers must now be accountable for quantified clinical information.
Collecting such data and determining how to use them to improve performance may
require a new mindset for many agencies, however. How should agencies approach
this new requirement?
PMID- 10185403
TI - But ... does it have meaning?
PMID- 10185404
TI - Management services organizations: providing economies of scale.
AB - Effective information management and other shared costs can reduce agencies'
operating expenses as well as make new products available while providing
opportunities to gain a competitive advantage. By taking a close look at ways of
controlling documentation, such as the use of a management services organization
for information system/computer-based management, agencies can prepare for the
challenges of the next century.
PMID- 10185405
TI - Legislating EMS. "EMS Efficiency Act of 1998" aims to improve prehospital
services.
PMID- 10185406
TI - To be or not to be ... seen.
PMID- 10185407
TI - Emergency management of athletic trauma: roles and responsibilities.
PMID- 10185408
TI - Guidelines for the appropriate care of an athlete with a suspected spine injury:
a report from the Inter-Association Task Force. National Athletic Trainers
Association.
PMID- 10185409
TI - Field management and priorities in trauma patient resuscitation.
PMID- 10185410
TI - Power of the published word.
PMID- 10185411
TI - Latex allergy: an emerging problem.
PMID- 10185412
TI - Managing the future. A discussion of how EMS and managed care organizations can
exist harmoniously.
PMID- 10185413
TI - The art of crowd control.
PMID- 10185414
TI - The challenge of justifying services.
PMID- 10185415
TI - No time to wait. An overview of recent studies and departmental programs designed
to improve prehospital response to cardiac emergencies.
PMID- 10185416
TI - Future of ACLS care. Interview by Mike Spivak.
PMID- 10185417
TI - Taking it to the street: advanced monitoring and 12-lead EKGs in prehospital
care.
AB - Prehospital care is becoming increasingly sophisticated, and ALS caregivers will
be proving advanced diagnostics and therapeutic modalities for patients,
including definitive treatments like thrombolytic therapy. To help make this
possible, we will need to use state-of-the-art diagnostic equipment. The medical
electronics industry in partnership with emergency medical services systems can
help reduce the morbidity and mortality associated with heart attack to improve
the quality of patients' lives.
PMID- 10185418
TI - Customer care. Patient satisfaction in the prehospital setting.
AB - The focus of the study was to prioritize six emergency medical service treatment
factors in terms of their impact upon patient satisfaction in the prehospital
setting. The six treatment areas analyzed were: EMS response time; medical care
provided on scene; explanation of care by the provider; the provider's ability to
reduce patient anxiety; the provider's ability to meet the patient's non-medical
needs; and the level of courtesy/politeness shown by the EMS provider toward the
patient. Telephone interviews were conducted with both patients and bystanders to
obtain their perception of how well the system met their needs. The study
analyzed how the six issues were rated and then evaluated the impact an
individual's low score in a category had on that person's overall rating of the
service provided. The overall satisfaction rating is not a calculated score, but
an overall score specified by the respondent. The effect each issue had on the
respondent's overall rating was determined by averaging the overall ratings for a
category's low scorers, averaging the overall ratings for high scorers and then
measuring the difference. Results of the study indicate that the factor with the
greatest negative impact on patient satisfaction came from a perceived lack of
crew courtesy and politeness. Respondents who indicated a fair to poor score in
this category decreased their overall score by 60.2%. Ratings in other categories
yielded the following results: When respondents rated the response time as fair
to poor, their average overall rating showed an 18.4% decrease. When respondents
rated the quality of medical care as fair to poor, their average overall rating
showed a decrease of 22.6%. When the crew's ability to explain what was happening
to the patient was rated as fair to poor, the average overall score dropped
33.6%. When the EMT's and medic's ability to reduce the patient's anxiety was
rated fair to poor, average overall score declined by 32.6%. Finally, when the
crew's ability to satisfy a patient's non-medical needs was rated as fair to
poor, the average overall score diminished by 37.4%.
PMID- 10185419
TI - EMS operations on the fireground.
PMID- 10185420
TI - Setting the pace for our future.
PMID- 10185421
TI - "How the donors see it".
PMID- 10185424
TI - On initiative.
PMID- 10185423
TI - Tax-exempt charities can offer employees 401(k) retirement plan.
AB - Here is a description of some recent changes in U.S. tax law that now allow tax
exempt non-profit organizations to improve one employee benefit--at a minimal
cost to the employer. Tax-exempt organizations can now offer employees 401(k)
retirement plans.
PMID- 10185422
TI - In-kind giving: it's a good thing ... but don't be naive.
AB - In-kind giving is of great importance to fund raisers, but it raises many red
flags. This article explores in-kind giving on both sides of the table, with
corporate givers and charitable takers, and suggests new ways of looking at these
gifts.
PMID- 10185425
TI - Manufacturing a special event success.
PMID- 10185426
TI - Fast, global, and entrepreneurial: supply chain management, Hong Kong style. An
interview with Victor Fung. Interview by Joan Magretta.
AB - Li & Fung, Hong Kong's largest export trading company, has been an innovator in
supply chain management--a topic of increasing importance to many senior
executives. In this interview, chairman Victor Fung explains both the philosophy
behind supply chain management and the specific practices that Li & Fung has
developed to reduce costs and lead times, allowing its customers to buy "closer
to the market." Li & Fung has been a pioneer in "dispersed manufacturing." It
performs the higher-value-added tasks such as design and quality control in Hong
Kong, and outsources the lower-value-added tasks to the best possible locations
around the world. The result is something new: a truly global product. To produce
a garment, for example, the company might purchase yarn from Korea that will be
woven and dyed in Taiwan, then shipped to Thailand for final assembly, where it
will be matched with zippers from a Japanese company. For every order, the goal
is to customize the value chain to meet the customer's specific needs. To be run
effectively, Victor Fung maintains, trading companies have to be small and
entrepreneurial. He describes the organizational approaches that keep the company
that way despite its growing size and geographic scope: its organization around
small, customer-focused units; its incentives and compensation structure; and its
use of venture capital as a vehicle for business development. As Asia's economic
crisis continues, chairman Fung sees a new model of companies emerging--companies
that are, like Li & Fung, narrowly focused and professionally managed.
PMID- 10185427
TI - The right mind-set for managing information technology.
AB - Too many managers in the West are intimidated by the task of managing technology.
They tiptoe around it, supposing that it needs special tools, special strategies,
and a special mind-set. Well, it doesn't, the authors say. Technology should be
managed-controlled, even--like any other competitive weapon in a manager's
arsenal. The authors came to this conclusion in a surprising way. Having set out
to compare Western and Japanese IT-management practices, they were startled to
discover that Japanese companies rarely experience the IT problems so common in
the United States and Europe. In fact, their senior executives didn't even
recognize the problems that the authors described. When they dug deeper into 20
leading companies that the Japanese themselves consider exemplary IT users, they
found that the Japanese see IT as just one competitive lever among many. Its
purpose, very simply, is to help the organization achieve its operational goals.
The authors recognize that their message is counterintuitive, to say the least.
In visits to Japan, Western executives have found anything but a model to copy.
But a closer look reveals that the prevailing wisdom is wrong. The authors found
five principles of IT management in Japan that, they believe, are not only
powerful but also universal. M. Bensaou and Michael Earl contrast these
principles against the practices commonly found in Western companies. While
acknowledging that Japan has its own weaknesses with technology, particularly in
white-collar office settings, they nevertheless urge senior managers in the West
to consider the solid foundation on which Japanese IT management rests.
PMID- 10185428
TI - Desperately seeking synergy.
AB - Corporate executives have strong biases in favor of synergy, and those biases can
lead them into ill-advised attempts to force business units to cooperate--even
when the ultimate benefits are unclear. But executives can separate the real
opportunities from the mirages, say Michael Goold and Andrew Campbell. They
simply need to take a more disciplined approach to synergy. These biases take
four forms. First comes the synergy bias, which leads executives to overestimate
the benefits and underestimate the costs of synergy. Then comes the parenting
bias, a belief that synergy will be captured only by cajoling or compelling
business units to cooperate. The parenting bias is usually accompanied by the
skills bias--the assumption that whatever know-how is required to achieve synergy
will be available within the organization. Finally, executives fall victim to the
upside bias, which causes them to concentrate so hard on the potential benefits
of synergy that they overlook the possible downside risks. In combination, these
four biases make synergy seem more attractive and more easily achievable than it
truly is. As a result, corporate executives often launch initiatives that
ultimately waste time and money and sometimes even severely damage their
businesses. To avoid such failures, executives need to subject all synergy
opportunities to a clear-eyed analysis that clarifies the benefits to be gained,
examines the potential for corporate involvement, and takes into account the
possible downsides. Such a disciplined approach will inevitably mean that fewer
initiatives will be launched. But those that are pursued will be far more likely
to deliver substantial gains.
PMID- 10185429
TI - The dawn of the e-lance economy.
AB - Will the large industrial corporation dominate the twenty-first century as it did
the twentieth? Maybe not. Drawing on their research at MIT's Initiative on
Inventing the Organizations of the 21st Century, Thomas Malone and Robert
Laubacher postulate a world in which business is not controlled through a stable
chain of management in a large, permanent company. Rather, it is carried out
autonomously by independent contractors connected through personal computers and
electronic networks. These electronically connected free-lancers-e-lancers-would
join together into fluid and temporary networks to produce and sell goods and
services. When the job is done--after a day, a month, a year--the network would
dissolve and its members would again become independent agents. Far from being a
wild hypothesis, the e-lance economy is, in many ways, already upon us. We see it
in the rise of outsourcing and telecommuting, in the increasing importance within
corporations of ad-hoc project teams, and in the evolution of the Internet. Most
of the necessary building blocks of this type of business organization--efficient
networks, data interchange standards, groupware, electronic currency, venture
capital micromarkets--are either in place or under development. What is lagging
behind is our imagination. But, the authors contend, it is important to consider
sooner rather than later the profound implications of how such an e-lance economy
might work. They examine the opportunities, and the problems, that may arise and
anticipate how the role of managers may change fundamentally--or possibly even
disappear altogether.
PMID- 10185430
TI - Right away and all at once: how we saved Continental.
AB - In 1993, when Greg Brenneman started working at Continental Airlines, it was the
most dysfunctional company he had ever seen. It had been through two bankruptcies
and ten presidents in ten years. There was next to no strategy. The company was
burning through money. And employee morale couldn't get any worse. Today
Continental is flying high. It posted revenues of $7.2 billion and a net income
of $385 million in 1997. It regularly ranks as one of the top five U.S. airlines
for key performance measures such as dispatch reliability. And employee turnover
has been drastically reduced. What happened? In this first-person account,
Brenneman, now Continental's president and COO, describes how he and the new team
at Continental's helm transformed the company "right away and all at once." More
specifically, he describes the five lessons he learned during this dramatic
turnaround. At the beginning, there was so much wrong with Continental that he
felt as if any one misstep could bring the whole effort down. But in a time of
crisis, when time is tight and money is tighter, you can't afford to mull over
complex strategy. With Gordon Bethune, Continental's chairman and CEO, Brenneman
devised the Go Forward Plan, a straightforward strategy focused on four key
elements: understanding the market, increasing revenues, improving the product,
and transforming the corporate culture. He admits that the plan wasn't
complicated--it was pure common sense. The tough part was getting it done. "Do it
now!" became the rallying cry of the movement, and the power of momentum has
carried Continental to success.
PMID- 10185431
TI - After the layoffs, what next?
AB - Harry Denton, the CEO in this fictional case study, has been caught off guard. As
the head of Delarks, a venerable department-store chain in the Midwest, he has
engineered a remarkable turn-around in only a year. Sales have rebounded, and
Wall Street is applauding. Sure, a few trees were felled in the process--to make
room for new growth, Denton had to clear out 3,000 pieces of what he privately
refers to as "dead-wood"--but he'd saved the company. Didn't people understand
that? Not exactly. When Delarks's head of merchandising defects to a competitor,
Denton is shocked to realize that many of the survivors, in fact, have had it
with him and with the company. The last straw was the recent closing of the
Madison store, which Denton announced without warning to anyone--not even the
company's head of HR, Thomas Wazinsky, a supposedly trusted adviser. In the wake
of that coup, store employees from Wichita to Peoria are wondering, Are we next?
The rumor mill says that many of them are considering leaving before Denton can
inflict the next blow. And senior managers are not immune to the fear and anger.
Even Wazinsky, one of the few links to Delarks's proud past, confesses to Denton,
"I'll bet you're thinking of firing me." Denton has to act--and fast. He calls a
"town meeting" for the 600 employees of the St. Paul store. The plan: rally the
troops. Instead, Denton is routed. Angry questions are hurled at the CEO, and he
is forced to beat a hasty retreat through the back door. Five experts offer
advice on how to revive morale at the successful but troubled company.
PMID- 10185432
TI - The hidden traps in decision making.
AB - Bad decisions can often be traced back to the way the decisions were made--the
alternatives were not clearly defined, the right information was not collected,
the costs and benefits were not accurately weighted. But sometimes the fault lies
not in the decision-making process but rather in the mind of the decision maker.
The way the human brain works can sabotage the choices we make. John Hammond,
Ralph Keeney, and Howard Raiffa examine eight psychological traps that are
particularly likely to affect the way we make business decisions: The anchoring
trap leads us to give disproportionate weight to the first information we
receive. The statusquo trap biases us toward maintaining the current situation-
even when better alternatives exist. The sunk-cost trap inclines us to perpetuate
the mistakes of the past. The confirming-evidence trap leads us to seek out
information supporting an existing predilection and to discount opposing
information. The framing trap occurs when we misstate a problem, undermining the
entire decision-making process. The overconfidence trap makes us overestimate the
accuracy of our forecasts. The prudence trap leads us to be overcautious when we
make estimates about uncertain events. And the recallability trap leads us to
give undue weight to recent, dramatic events. The best way to avoid all the traps
is awareness--forewarned is forearmed. But executives can also take other simple
steps to protect themselves and their organizations from the various kinds of
mental lapses. The authors show how to take action to ensure that important
business decisions are sound and reliable.
PMID- 10185433
TI - How to kill creativity.
AB - In today's knowledge economy, creativity is more important than ever. But many
companies unwittingly employ managerial practices that kill it. How? By crushing
their employees' intrinsic motivation--the strong internal desire to do something
based on interests and passions. Managers don't kill creativity on purpose. Yet
in the pursuit of productivity, efficiency, and control--all worthy business
imperatives--they undermine creativity. It doesn't have to be that way, says
Teresa Amabile. Business imperatives can comfortably coexist with creativity. But
managers will have to change their thinking first. Specifically, managers will
need to understand that creativity has three parts: expertise, the ability to
think flexibly and imaginatively, and motivation. Managers can influence the
first two, but doing so is costly and slow. It would be far more effective to
increase employees' intrinsic motivation. To that end, managers have five levers
to pull: the amount of challenge they give employees, the degree of freedom they
grant around process, the way they design work groups, the level of encouragement
they give, and the nature of organizational support. Take challenge as an
example. Intrinsic motivation is high when employees feel challenged but not
overwhelmed by their work. The task for managers, therefore, becomes matching
people to the right assignments. Consider also freedom. Intrinsic motivation--and
thus creativity--soars when managers let people decide how to achieve goals, not
what goals to achieve. Managers can make a difference when it comes to employee
creativity. The result can be truly innovative companies in which creativity
doesn't just survive but actually thrives.
PMID- 10185434
TI - Strategy as a portfolio of real options.
AB - In financial terms, a business strategy is much more like a series of options
than like a single projected cash flow. Executing a strategy almost always
involves making a sequence of major decisions. Some actions are taken immediately
while others are deliberately deferred so that managers can optimize their
choices as circumstances evolve. While executives readily grasp the analogy
between strategy and real options, until recently the mechanics of option pricing
was so complex that few companies found it practical to use when formulating
strategy. But advances in both computing power and our understanding of option
pricing over the last 20 years now make it feasible to apply real-options
thinking to strategic decision making. To analyze a strategy as a portfolio of
related real options, this article exploits a framework presented by the author
in "Investment Opportunities as Real Options: Getting Started on the Numbers"
(HBR July-August 1998). That article explained how to get from discounted-cash
flow value to option value for a typical project; in other words, it was about
reaching a number. This article extends that framework, exploring how, once
you've worked out the numbers, you can use option pricing to improve decision
making about the sequence and timing of a portfolio of strategic investments.
Timothy Luehrman shows executives how to plot their strategies in two-dimensional
"option space," giving them a way to "draw" a strategy in terms that are neither
wholly strategic nor wholly financial, but some of both. Such pictures inject
financial discipline and new insight into how a company's future opportunities
can be actively cultivated and harvested.
PMID- 10185435
TI - How hospital investigative unit reduces thefts and property crime.
PMID- 10185436
TI - Software programs assess hospital security weaknesses.
PMID- 10185437
TI - Weigh these security factors first when designing new parking structures.
PMID- 10185438
TI - Crime prevention team tackles crime inside and outside med center.
PMID- 10185439
TI - JCAHO accreditation and ISO 9000 certification: an update.
AB - With hospital security now considered by the JCAHO as part of the hospital's
total environment of care, security directors must be prepared to answer
questions about areas where multidisciplinary solutions are sought. At the same
time, it may pay to become familiar with ISO 9000 certification, quality
standards that may in the future complement JCAHO accreditation. In this report,
we'll provide detailed information that may stand you in good stead in the years
ahead.
PMID- 10185440
TI - IAHSS President Flores: 'hospital security at risk; stress value-added'.
PMID- 10185441
TI - Newborn security: steps toward minimizing your vulnerability.
PMID- 10185442
TI - Prepare for the worst: fortify newborn security.
PMID- 10185443
TI - Baby switch plagues VA facility--three years later.
PMID- 10185444
TI - Is anonymous reporting to JCAHO feasible?
PMID- 10185445
TI - C-sections give way to VBACs and better quality.
PMID- 10185446
TI - Case managers crucial to Medicaid program for disabled.
PMID- 10185447
TI - Approach VBAC deliveries cautiously, experts say.
PMID- 10185448
TI - Educate the users of performance data.
PMID- 10185449
TI - JCAHO may develop new compliance standards.
PMID- 10185450
TI - The AIDS pandemic: changes in the believability and use of information sources.
AB - Over 20,000 Americans under 25 years old are infected with HIV every year. In
1994, AIDS was the number one killer of adults between the ages of 25 and 44
years old. Education concerning HIV is critical to the prevention of AIDS. Both
the public and private sectors, including government agencies, cause-related
organizations, medical professionals, and promotion specialists must determine
the best information sources to educate young people. However, with many
television shows that appeal to young adults condoning casual sex, it is
increasingly difficult to generate motivation to act responsibly. This paper
examines the effectiveness of information sources, sponsored by both the
government and private organizations, about HIV. Given the impact of media
publicity regarding the AIDS virus and the "hard-hitting" messages and public
service announcements about AIDS, implications about ethical issues, public
policy issues, and media strategies to educate the public about AIDS are
discussed. While publicity and specific types of television programming were
found to be the most believable and most often used information sources for
health issues, there are many strategic implications concerning promotion
strategies, targeting, and positioning for both the public and private sectors.
PMID- 10185451
TI - Tackling no-show behavior: a market-driven approach.
PMID- 10185452
TI - Patient sources of information and decision factors in selecting cosmetic
surgeons.
AB - This paper presents the results of an exploratory study designed to examine
influential information sources and decision factors in the selection of plastic
surgeons for cosmetic versus medical procedures. Physician referrals were found
to be the most influential sources of information for both groups. Word-of-mouth
and magazine and newspaper articles were also important information sources for
cosmetic patients. Primary selection factors were significantly different between
groups, with board certification the most influential for cosmetic patients and
recommendation by physician most influential for medical patients.
PMID- 10185453
TI - Affect, attribution, and disconfirmation: their impact on health care services
evaluation.
AB - The paper simultaneously assesses the influence of affect toward the health care
provider, attributions of the health care provider, and disconfirmation on
patient satisfaction with the health care provider and their intention to return
to the health care provider in the future. The findings indicate affect and
disconfirmation play a role in patients' judgements, but attribution does not.
Also, patients appear to have a zone of tolerance as to the events that
constitute the health care service delivery. This suggests that health care
providers may have a zone of variation in the action they take and still maintain
a satisfied patient.
PMID- 10185454
TI - Social welfare in a managerial society.
AB - Managerialism is a dominant ideology in the institution of social welfare and the
profession of social work. Managerialism includes the tools and traditions of
modern management. It is also a way of viewing the social world. Managerialism is
a useful but limited ideology in social work and social welfare. The benefits of
this perspective include the ordering and sanctioning of professional social
workers and the application of sophisticated management tools in the institution
of social welfare. Managerialism threatens the historic mission and identity of
social work and social welfare. The field is challenged to find an institutional
niche for those aspects that are outside the mainstream of the commercial
culture.
PMID- 10185455
TI - The impact of pharmaceutical direct advertising: opportunities and obstructions.
AB - The recent dramatic increase in direct-to-consumer advertising of prescription
drugs has important implications for the pharmaceutical industry, physicians, and
patients. One goal of direct advertising is to increase patient awareness of
specific brands of medications while hoping to promote a greater frequency in
office visits, presumably to specifically request these medicines. This paper
will examine some of the benefits as well as drawbacks of the new, direct-to
customer pharmaceutical advertising, suggesting that in an era increasingly
defined by the demands of managed care, such direct advertising may prove to have
limited long-term effects.
PMID- 10185456
TI - Alzheimer's disease. Three-score years and then?
PMID- 10185457
TI - All quiet on the western front?
PMID- 10185458
TI - Public accountability. Blowing in the wind. Interview by Janet Snell.
PMID- 10185459
TI - NHS costs. Age-old myths.
AB - The ageing of the UK population will not automatically lead to increased demands
on the NHS. If people live longer they stay healthy longer. The cost of caring
for them is shifted, not increased. It has not been proven that an ageing
population and the costs of medical technology justify the NHS receiving above
inflation funding increases year after year.
PMID- 10185460
TI - On the evidence. Cardiac rehabilitation.
PMID- 10185461
TI - Human resources. Happy families or snap?
AB - Family-friendly initiatives are popular with staff, but little research has been
done to determine their effect. Employers should ask staff what sort of schemes
would be most useful to avoid wasting managers' time. Under half the employers
surveyed offered creches, nurseries or holiday play schemes. Where they are
offered, they are very popular with staff. Employers should specify what they
offer in advertisements for staff.
PMID- 10185462
TI - Commissioning. Share options.
AB - A system of effective commissioning will be crucial to the reorganised NHS. Any
system must combine flexibility for primary care groups with financial stability
for trusts. A four-part funding stream for PCGs could be effective.
PMID- 10185463
TI - Primary care. Red herring.
PMID- 10185464
TI - Leadership. Great dictators.
PMID- 10185465
TI - Data briefing. The internal market.
PMID- 10185466
TI - Are you better off than you were a year ago?
PMID- 10185467
TI - Beyond measurement: performance-based planning for better community outcomes.
PMID- 10185468
TI - Leadership for a healthy 21st century.
PMID- 10185469
TI - Strategies for outcomes measurement: how seven systems do it.
PMID- 10185470
TI - Investing in tomorrow: healthcare tithing.
PMID- 10185471
TI - Inside/out: change agents and community partnerships.
PMID- 10185472
TI - Fight, copy or cooperate? How hospitals can respond to poaching by PPMs.
PMID- 10185473
TI - Models that work.
PMID- 10185474
TI - Emerging leaders.
PMID- 10185475
TI - Cleaning up the red ink in primary care.
PMID- 10185476
TI - What business did you say we were in?
PMID- 10185477
TI - Breaking ranks.
PMID- 10185478
TI - The metamorphosis of chronic care. Healthcare's next big hurdle.
PMID- 10185479
TI - The Balanced Budget Act and beyond: Congressional initiatives in chronic care.
PMID- 10185480
TI - The metamorphosis of chronic care. A promising beginning: an uncertain future.
PMID- 10185481
TI - The metamorphosis of chronic care. Managed care and chronic care.
PMID- 10185482
TI - The metamorphosis of chronic care. Tools for evaluating chronic care networks.
PMID- 10185483
TI - Demanding medical excellence: a conversation with Michael Millenson. Interview by
Joe Flower.
PMID- 10185484
TI - The civic roles of healthcare organizations.
PMID- 10185485
TI - Healthcare in a world of chaos: Jim Taylor talks about the 500 year delta.
PMID- 10185486
TI - Turn word of mouth into a marketing advantage.
PMID- 10185487
TI - Marketing myopia.
PMID- 10185488
TI - How mature is your organization's prevention effort? Four stages of managed care
health promotion.
AB - Rooted in prevention since the 1973 HMO Act, managed care has weathered seasons
enough to put down roots in patient education and preventive services. Now it
shows a readiness for re-potting. For health promotion to reach full maturity and
realize its highest calling, its roots need to spread into the community.
Analysts have posited four stages of managed care market penetration; similarly,
I propose four stages of maturation in managed care-based prevention initiatives
(Table 1). These stages of prevention are based on an analysis of more than 100
presentations from a series of "Managed Care to Managed Health" conferences
sponsored by The Institute for Research and Education, Health-System Minnesota in
Minneapolis. The following descriptions of the stages of maturation illustrate
the development of prevention efforts--from patient education and preventive
services in early stages to improving the health of enrollees and ultimately the
community in later stages.
PMID- 10185489
TI - The hunger for strategic leadership.
PMID- 10185490
TI - Regeneration as therapy.
PMID- 10185491
TI - Hospital turns market into superfacility.
PMID- 10185492
TI - Wanted: facility managers ready to tackle the future. Requirements: vision,
savvy, and nonstop learning.
PMID- 10185493
TI - Going up (maybe). Is elevator safety a myth? Check out the facts.
PMID- 10185494
TI - Attention, shoppers! Smarts tips on how to wade through 'new, improved' products.
PMID- 10185495
TI - Emergency in the ER! Standards for handling the contaminated patient.
PMID- 10185496
TI - After the needlestick. How one hospital handles it.
PMID- 10185497
TI - Managerial epidemiology in the health administration curriculum.
AB - With the rapid changes in health care delivery systems an appreciation and
specialized understanding of epidemiology is a necessary requirement for health
care administration practitioners. Managed care compels health care managers to
focus on delivering health care services to populations and not individuals. The
health care administrator today must focus on population-based management, and no
longer can afford to ignore epidemiologic measurements. This article presents the
development and implementation of a specialized course in managerial
epidemiology. The specific phases of course development, course content, and
course framework are presented and discussed.
PMID- 10185498
TI - Optimal internship/residency-interview assignments for health care administration
student placement.
AB - Interview assignment is an issue of importance to all health care administration
programs containing internships and residencies. More generally, many master's
and doctoral level educational programs in social work, clinical psychology, and
other health fields are faced with the interview assignment problem. We present a
linear programming approach, which has been employed at the Baruch College/Mt.
Sinai School of Medicine Graduate Program in Health Care Administration, for
determining optimal internship/residency-interview assignments. Specifically, a
capacitated transportation model, with the objective of maximizing the overall
utility of the interview assignments, was implemented. This research is intended
to demonstrate to academic program directors dealing with such problems the value
of this objective method and to assist educators in their efforts to optimize the
student internship/residency placement process at their various institutions.
PMID- 10185499
TI - An integrative capstone project for an undergraduate health care administration
program.
PMID- 10185500
TI - Theory of health insurance.
AB - The conventional explanation for purchasing insurance is to transfer risk.
Psychologists, however, have shown that this explanation does not match actual
behavior. They find that people generally prefer the risk of no loss at all to
the certainty of a smaller actuarially equivalent loss, a situation exactly
opposite to the one represented by the purchase of insurance. Nevertheless,
people do purchase insurance, so there must be an explanation other than risk
transfer for purchasing it. Of the explanations so far advanced, however, none
have yet developed a wide acceptance. Regardless of risk issues, people will be
more likely to purchase insurance when the premium is low compared to the value
of the coverage to the consumer. Moral hazard raises the premium, as does adverse
selection. The presence of either makes the purchase of insurance less likely.
With health insurance, the tax subsidy can reduce the effective premium to less
than the actuarially fair cost of insurance. This would increase the likelihood
that health insurance is purchased. Finally, because of the value we place on our
health, we desire access to a full range of health care. Health insurance is
often the only affordable way of gaining access to this care, given the high
costs of many of these procedures.
PMID- 10185501
TI - Dilemmas in health management education: past, present and future.
PMID- 10185502
TI - Out of the box: health management education in the 21st century.
PMID- 10185503
TI - Andrew Pattullo and "A strategy for building a profession".
PMID- 10185504
TI - The evolution of health care reforms in Greece: charting a course of change.
AB - An examination of Greece's experience with health care reform planning over the
past half century reveals a remarkable consistency in reform themes pursued by
planners. However, few of the plans resulted in legislation, and of the
legislation that was passed even fewer were implemented. The present paper traces
out reform plans since the early 1950s and argues that legislative and
implementation failures have been due to a lack of political will, insufficient
attention to consensus-forming mechanisms, and inadequate consideration of the
technical, administrative, and institutional feasibility of reform plans. By
contrast, developments in the 1990s, which have seen three pieces of health care
reform legislation, suggest that processes of health care planning and change are
becoming more focused, rational and pragmatic. Macroeconomic constraints, and
consensus on broader economic policies focusing on the EU convergence
requirements have produced a consensus regarding the imperative of change in the
health sector, and have given rise to mechanisms which facilitate the task of
implementation. The most recent health care reform act (of 17 July 1997) is less
radical than many of its predecessors, but includes issues that had entered the
health care reform agenda as early as 1952, as well as the more current issues of
health care reform agenda as early as 1952, as well as the more current issues of
health sector rationalization. Implementation of the most recent legislative act
has already begun.
PMID- 10185505
TI - Health sector reform in the former Soviet Republics of Central Asia.
AB - Health services in the former Soviet Republics of Central Asia face many
challenges, not least a rising burden of disease and severe economic constraints.
Each government has developed proposals for reform. This paper describes the key
elements of the proposals developed in each country. They have many features in
common, such as financing based on social insurance, although they also have many
differences, reflecting national political, economic and historical
circumstances. While most attention so far has concentrated on the design of the
proposed systems, it is argued here that there has been inadequate attention to
the obstacles to implementation. These stem from the many adverse factors in the
context within which reforms are taking place, weaknesses in the process of
reform, and failure to involve the groups whose actions will be necessary for
success. It is argued that governments and those advising them must place greater
emphasis on the challenges of implementation, including the development of a much
better understanding of the context within which change must take place.
PMID- 10185506
TI - Health financing policy formulation in the Eastern Caribbean.
AB - Stakeholders formulating policies on national health insurance (NHI) in the
Eastern Caribbean have circled the abstract concept called NHI like the
proverbial blind men explaining the elephant. Definitions of NHI have shifted
depending on their perspectives and philosophical leanings, their understanding
of the issues, and their degree of influence on the process. Based on NHI
feasibility studies, market research, and stakeholder analysis conducted in five
countries, this article analyses the policy formulation stage of NHI development
in these tiny countries. Given the level of economic development and the existing
administrative capacity of the governments, this 'phase one' NHI could be a
pragmatic first step in introducing a health insurance component into the social
security systems of the countries, and gradually reforming other aspects of the
health sector. The article is structured around key questions which help to
define the positions and relationships of key stakeholders, and then evaluate NHI
plans in terms of economic viability, equity, administrative feasibility and
efficiency, cost containment incentives, and political palatability. These are
the elements that--in combination with economic and political context--will
determine the success or failure of NHI in the Eastern Caribbean.
PMID- 10185507
TI - The first private sector health insurance company in Ghana.
AB - This article analyses the development of Ghana's first private sector health
insurance company, the Nationwide Medical Insurance Company. Taking both policy
and practical considerations into account (stakeholders' perspectives, economic
viability, equity and efficiency), it is structured around key questions which
help to define the position and roles of stakeholders--the insurance agency
itself, contributors, beneficiaries, and providers--and how they relate to one
another and the insurance scheme. These relationships will to a large extent
determine Nationwide's long-term success or failure. By creating a unique
alliance between physician providers and private sector companies, Nationwide has
used employers' interest in cost containment and physicians' interest in
expanding their client base as an entree into the virgin territory of health
insurance, and created a hybrid variety of private sector insurance with some of
the attributes of a health maintenance organization or managed care. The case
study is unusual in that, while public sector programs are often open to academic
scrutiny, researchers have rarely had access to detailed data on the
establishment of a single private sector insurance company in a developing
country. Given that Ghana is planning to launch a national health insurance plan,
the article concludes by considering what the experience of this private sector
initiative might have to offer public sector planners.
PMID- 10185508
TI - The sector-wide approach in health: what is it? Where is it leading?
AB - This paper describes early experience with the Sector-Wide Approach (SWAp), an
emerging trend in development practice in low-income countries. The paper
describes what a SWAp is, and why it is now being pursued. The SWAp is
characterized as a sustained government-led partnership with donor agencies and
other groups. By applying sector-wide policies to an expenditure framework and
national implementation systems, explicit health sector reforms are undertaken to
meet sectoral and national development objectives. The approach has changed the
dynamic between governments and donor agencies, requiring systemic changes in
policy-making and management in both governments and donor agencies. With the
SWAp, ongoing joint assessment and negotiations around sectoral plans and review
of performance replaces the old way of preparing and supervising projects. Early
experiences in countries undergoing SWAps are discussed, including the problem of
reconciling priority programs and old practices with broader health sector
reforms and new ways of managing development assistance. The paper concludes by
identifying some of the key challenges for the future of SWAps.
PMID- 10185509
TI - Swedish models of health care reform: a review and assessment.
AB - Resource constraints and the necessity to improve efficiency and effectiveness
have provided challenges for the Swedish health care system during the 1990s.
Whereas there are no comprehensive reforms of funding and organization, measures
have been taken at both national and regional level to meet these challenges.
Decentralization has been a core issue in long-term reforms and current changes
can be seen as continuing this pattern. As a consequence different solutions are
sought in the various county councils (locally elected self-government bodies
financing and procuring health services). In about one third of these county
councils some sort of purchaser-provider models have been introduced. Emerging
evaluation reports claim that the models have succeeded in improving efficiency;
making the system more patient-oriented; and enhancing cost-consciousness. The
roles of politicians, managers and professionals are also more clear, according
to the proponents. However, there are also problems with more difficulties in
controlling costs, and with inadequate remuneration systems. Over time the
purchaser-provider schemes have matured, developing from emphasizing short-term
tendering, negotiations and detailed contracts to more comprehensive agreements
based on mutual commitments to improve health services. Rhetoric has changed;
competition has been replaced by co-operation. The lure of the market concept has
diminished. Similarities can be seen between county councils with and without
purchaser-provider models.
PMID- 10185510
TI - Workplace performance effects from chronic depression and its treatment.
AB - Utilizing data from a clinical trial and an econometric model incorporating the
impact of a medical intervention and regression to the mean, we present evidence
supporting the hypotheses that for chronically depressed individuals: (i) the
level of perceived at-work performance is negatively related to the severity of
depressive status; and (ii) a reduction in depressive severity improves the
patient's perceived work performance. Improvement in work performance is rapid,
with about two-thirds of the change occurring already by week 4. Those patients
having the greatest work improvement are those with both relatively low baseline
work performance and the least severity of baseline depression.
PMID- 10185511
TI - Creaming, skimping and dumping: provider competition on the intensive and
extensive margins.
AB - Reimbursement incentives influence both the intensity of services and who is
treated when patients differ in severity of illness. The social optimum is
compared to the private Cournot-Nash solution for three provider strategies:
creaming--over-provision of services to low severity patients; skimping--under
provision of services to high severity patients; and dumping--the explicit
avoidance of high severity patients. Cost-based reimbursement results in
overprovision of services (creaming) to all types of patients. Prospectively paid
providers cream low severity patients and skimp high severity ones. If there is
dumping of high severity patients, then there will also be skimping.
PMID- 10185512
TI - Does increasing the beer tax reduce marijuana consumption?
AB - Previous studies suggest that alcohol and marijuana are economic substitutes, so
recent policies restricting the availability of alcohol have led to an increase
in the amount of marijuana consumed. Using micro-level data from the National
Longitudinal Survey of Youth (NLSY) to estimate individual demand equations for
alcohol and marijuana, this research finds that alcohol and marijuana are
economic complements, not substitutes. Further, this research finds that
increases in the federal tax on beer will generate a larger reduction in the
unconditional demand for marijuana than for alcohol in percentage terms.
PMID- 10185513
TI - Agency in health care. Examining patients' preferences for attributes of the
doctor-patient relationship.
AB - Recently, some health economists have re-examined the nature of the agency
relationship in health care. This paper presents a study conducted to establish
the relative value to patients of various attributes of the general practice
consultation. In the sample of patients recruited, the most important attribute
was 'being able to talk to the doctor', whilst 'who chooses your treatment' was
the least important. Although patients preferred more information to less, only
females and highly qualified respondents preferred to choose the treatment
themselves. The results of this study have implications for the education of
doctors in communication skills and for further research into the agency
relationship in health care.
PMID- 10185514
TI - QALYs versus HYEs--what's right and what's wrong. A review of the controversy.
AB - The paper uses an axiomatic approach to the description of individual preferences
for health status sequences to resolve the major issues at state in the recent
controversy over QALYs versus HYEs. While the HYE accounts for an individual's
time preference for health, QALY scores based on the time trade-off method will
generally differ from the number of HYEs. HYEs do not represent preferences for
health under risk unless the utility function for reference flows of health is
linear. Collapsing the two-step HYE assessment procedure into a single step
entails a loss of information as regards the utility of a health status sequence.
Although the procedure does represent preferences for health, it fails to supply
a description in terms of HYEs in the case of risk. As a remedy, a modified HYE
approach is proposed.
PMID- 10185515
TI - Time spent on waiting lists for medical care: an insurance approach.
AB - In this paper, we develop a simple model of the benefits and costs of being on a
waiting list. The model shows that complex factors are in operation, implying
that a shorter waiting time need not necessarily be preferred to a longer waiting
time. We also present an empirical study, where a sample of Swedes are offered
the possibility of purchasing private insurance, thus reducing waiting time for
surgery beyond the three-month guarantee offered by the public sector health care
system. Respondents could choose between two insurance contracts. A 'spike'
model, where the probability of a zero WTP is strictly positive, was developed
and estimated to obtain demand functions for private insurance.
PMID- 10185516
TI - The versatile doctor's guide to ethnic diversity.
PMID- 10185517
TI - I won back my license--and my good name.
PMID- 10185518
TI - Doctors' incomes: who's up, who's down.
PMID- 10185519
TI - Doctors and divorce. Goodbye to medicine, or to your marriage?
PMID- 10185521
TI - How doctors botch their employment interviews.
PMID- 10185520
TI - Health-care costs. It's deja vu all over again.
PMID- 10185522
TI - Just another wacky week in Washington.
PMID- 10185523
TI - Thinking the (previously) unthinkable: what if you get fired?
PMID- 10185524
TI - High incomes, low costs: how do they do it?
PMID- 10185525
TI - Can contact capitation conquer costs?
PMID- 10185526
TI - Charge what you will ... reimbursements are shrinking.
PMID- 10185527
TI - Fee battles with the Blues. Out West, organized medicine joins the fray ... and
back East, the feds attack a doctor union.
PMID- 10185528
TI - Patient satisfaction. They're happier with indemnity care? Says who?
PMID- 10185529
TI - Your next Medicare headache: Y2K.
PMID- 10185530
TI - Patient advocate--or dysfunctional doctor?
PMID- 10185531
TI - For these doctors and patients, health means "personal best".
PMID- 10185532
TI - Equal shares or productivity? How doctors divide income.
PMID- 10185533
TI - The contracting gamble: what your colleagues are betting on.
PMID- 10185534
TI - How to avoid the malpractice "snakebite".
PMID- 10185535
TI - When machines become doctors, will doctors become machines?
PMID- 10185536
TI - Physician recruitment. Is the managed-care backlash working in specialists'
favor?
PMID- 10185537
TI - The best job may be the one you already have.
PMID- 10185538
TI - Is American medicine overrated? These doctors think so.
PMID- 10185539
TI - Media hatchet job. A doctor strikes back--and wins big.
PMID- 10185540
TI - How to feel really good after a vacation.
PMID- 10185541
TI - Taming the disruptive doctor.
PMID- 10185542
TI - How successful practices plan their success.
PMID- 10185543
TI - Year 2000 could jeopardize Medicare payments.
PMID- 10185545
TI - Computerizing the transfusion service department: one laboratory's experience.
AB - Implementing new procedures in the workplace often presents unanticipated
challenges. As one-half of the "odd-couple of laboratory project management," the
author outlines with humor the trials and tribulations encountered when she and a
coworker agreed to computerize the transfusion service in her hospital.
PMID- 10185544
TI - Validating your laboratory information system.
AB - These tips for streamlining the process of computer validation offer an organized
approach to a sometimes overwhelming task. Simplifying computer validation is
just a matter of good planning and breaking the task into manageable steps.
PMID- 10185546
TI - As others see us, Part 3. The competitive marketplace: an exciting future for
laboratory medicine.
AB - Timely anticipation of patient needs and fair pricing of services will ensure
survival of the on-site hospital laboratory in the coming era of managed
healthcare. Management education and efficient operation are the keys to a bright
future.
PMID- 10185547
TI - MLO's survey of computer use in the laboratory.
PMID- 10185548
TI - Intranets: virtual procedure manuals for the pathology lab.
AB - A novel system exists for replacing standard written operation manuals using a
computerized PC-based peer-to-peer network. The system design is based on
commonly available hardware and software and utilizes existing equipment to
minimize implementation expense. The system is relatively easy to implement and
maintain, involves minimal training, and should quickly become a financial asset.
In addition, such a system can improve access to laboratory procedure manuals so
that resources can be better used on a daily basis.
PMID- 10185549
TI - How to handle problem staffers.
PMID- 10185550
TI - Aetna takes exit cue. Low reimbursement rates cause nine-state pullback.
PMID- 10185551
TI - The status of kid care. Many states implement 'place-holder' programs as first
step in expansion plans.
PMID- 10185552
TI - Farewell to controversy. Joint Commission decides to drop its IMSystem.
PMID- 10185554
TI - Setting the standard. VA system to streamline credentialing of federal docs.
PMID- 10185553
TI - Paltry sums. Average fraud settlements don't burden most hospitals.
PMID- 10185555
TI - HMO study finds $768 million loss.
PMID- 10185556
TI - Gaining from loss. Large creditor could benefit most from bankruptcy.
PMID- 10185557
TI - Highmark settles charges; ex-VP pleads guilty.
PMID- 10185558
TI - AHCPR makeover proposed. Frist introduces bill to revamp, refocus federal agency.
PMID- 10185559
TI - Old hands, new ventures. Hospital veterans launch five companies in Nashville.
PMID- 10185560
TI - Splitting pairs. When a merger falls apart, there are more losers than the
hospitals involved.
PMID- 10185561
TI - Open to alternatives.
AB - Under pressure from consumers, a growing number of health plans are offering a
variety of nontraditional treatments, such as acupuncture and Chinese herbal
medications. Although alternative medicine still has its critics because many
treatments are still scientifically untested, some estimates put the size of the
market at $24 billion, a figure projected to increase 15% per year.
PMID- 10185562
TI - Healing broken hearts. Hospitals, payers consider the latest high-tech lasers.
PMID- 10185564
TI - A mixed bag. 2nd-quarter earnings vary widely by healthcare sector.
PMID- 10185563
TI - Harvard stint tests CFO.
PMID- 10185565
TI - Baptist probe escalates. Unindicted co-conspirators named in kickback case.
PMID- 10185566
TI - AHA shuffle. Association loses executive, moves office, cuts staff.
PMID- 10185567
TI - Lewis named AHA chairwoman-elect.
PMID- 10185568
TI - Auditing the auditors.
AB - An independent auditor's opinion is supposed to be the gold standard in
healthcare accounting. Such audits provide reasonable assurance that financial
statements are accurate, which is particularly important in not-for-profit
healthcare because most organizations don't have shareholder oversight. But the
recent firing of a Big Five accounting firm by a major healthcare system in
bankruptcy reorganization raises questions about the credibility of external
audits.
PMID- 10185569
TI - Sparks flies with PhyCor docs. Ark. hospital hires almost one-third of clinic's
physicians.
PMID- 10185570
TI - Providers try to take Dare. Two teams vie for CON approval to build hospital in
N.C.
PMID- 10185571
TI - Trouble in the East Bay. Kaiser's alliance talks with Tenet hospital break down.
PMID- 10185572
TI - AHA, members compromise on money shift.
PMID- 10185573
TI - Lifting the Internet ban. HCFA drafts policy allowing on-line info transfer.
PMID- 10185574
TI - Docs on the hustings. More physicians seek office to influence health policy.
PMID- 10185575
TI - Accentuate the negative. Community supported conversion after understanding the
hospital's problems.
PMID- 10185576
TI - Matching consolidation with consolidation. Purchasing survey shows hospital
merger, integration up ante for buying groups.
PMID- 10185577
TI - Setting up a one-stop shop. Continuum will offer purchasing, distribution option.
PMID- 10185578
TI - Home care takes nose dive. Deals drop amid payment cuts, regulatory uncertainty.
PMID- 10185579
TI - A bumpy road ahead. Moody's reports cite dangers in rush to integrate.
PMID- 10185580
TI - Quality under scrutiny. Reports: plans' quality stagnant; innovation lacking.
PMID- 10185581
TI - VHA seeks boost via Internet entry.
PMID- 10185582
TI - Heavyweights get hit. Moody's downgrades CHW, Henry Ford over dim outlooks.
PMID- 10185583
TI - Speedy recovery. Obscure rule helps Houston hospital regain accreditation.
PMID- 10185584
TI - What hospitals won't do for a merger. Deals involving Catholic facilities often
mean a loss of reproductive services.
AB - As Catholic and non-Catholic hospitals pursue mergers or partnerships with one
another, the facilities are discovering a major culture clash, prompting a new
set of operating rules. At the heart of it all are prohibitions the Catholic
Church slaps on certain reproductive services, such as tubal ligations, abortions
and some fertility programs. Sometimes the hurdles prove insurmountable.
PMID- 10185585
TI - Prudential joins HMO exit queue.
PMID- 10185586
TI - Stoll honored with Harry J. Harwick Award.
PMID- 10185587
TI - Captive market. Despite setbacks, provider of prison healthcare services predicts
strong growth.
PMID- 10185588
TI - Welcome to Shangri-La. Some urban hospitals are offering luxury suites and a wide
range of amenities to patients who check in.
PMID- 10185589
TI - Paying a premium. Small business bears brunt of insurance rate increases.
PMID- 10185590
TI - A compliance problem. HHS, others rule out CFOs, counsels as ethics czars.
PMID- 10185591
TI - A pause in the action. Adventist focuses on assimilating recent acquisitions.
PMID- 10185592
TI - Sweetening the pot. Suppliers boost salaries moderately but stir in perks.
PMID- 10185594
TI - CHI buys Jewish Hospital. Medicare, other declining payments cited for sale.
PMID- 10185593
TI - Pool party. More hospitals, health systems buying capital in bulk.
PMID- 10185595
TI - And the winner is ... Tenet. For-profit chain bids $345 million for AHERF
facilities.
PMID- 10185596
TI - Free from state control. Kansas Med Center's new liberty ups opportunities.
PMID- 10185597
TI - Searching for better bait. Systems struggling to lure docs, trustees to
integration.
PMID- 10185598
TI - HMO exodus continues.
PMID- 10185599
TI - Report: HCFA isn't ready for year 2000.
PMID- 10185600
TI - On-line physician's office. Internet venture packages doc communications
services.
PMID- 10185601
TI - Big deal for HBO & Co. Company to pay $1 billion in stock for Access Health.
PMID- 10185602
TI - Tales of tattle-tales. Hospitals say anti-dumping rules forces them to snitch.
PMID- 10185603
TI - Choice cuts? New Medicare program could limit senior options.
PMID- 10185604
TI - Not willing to fight. Backers of Ark. HMO provider law give up legal battle.
PMID- 10185605
TI - Buying trouble. Differing perceptions about CDRs (Clinical Data Repositories)
complicate purchases, impede advances.
PMID- 10185606
TI - VHA hits the links. Electronic network will be accessible through Internet.
PMID- 10185607
TI - Summit saga ending. Deal would link powerful Bay Area hospitals in system.
PMID- 10185608
TI - Offering a comfort zone. La. senior center services, scope push boundaries.
PMID- 10185609
TI - Governance set for new AHA unit.
PMID- 10185610
TI - Uninsureds' number is up. Census Bureau reports shows spike, sparks call to
action.
PMID- 10185611
TI - Bugged. Congress, industry ridicule HCFA's Y2K argument.
PMID- 10185612
TI - Coming to terms. Hospitals groups arrive at a Medicare wage-index compromise
everyone hates.
PMID- 10185613
TI - PPMs on the rebound. Companies learn from mistakes, develop new strategies.
AB - Physician practice management companies, once Wall Street's darlings, are now
running into the reality of risk contracts and declining reimbursements. Those
and other roadblocks have reduced profits to a rumor for many companies. As a
result, the industry is being forced to change its core strategies, while some
observers even question whether PPMs will survive as relevant players.
PMID- 10185614
TI - Kaiser losses mount. Managed-care giant's red ink could match or top '97 total.
PMID- 10185615
TI - Survey: most hospitals will meet Y2K deadline.
PMID- 10185616
TI - 1998 Design Awards.
PMID- 10185617
TI - Making it a federal case. Suit alleges widespread fraud by Columbia, Quorum.
AB - A federal whistleblower lawsuit unsealed last week alleges widespread Medicare
fraud at two of the nation's largest for-profit hospital companies, Columbia/HCA
Healthcare Corp. and Quorum Health Group--both relatives of Hospital Corporation
of America. The case shows how hospitals' legal troubles have spread since the
advent of Medicare's prospective payment system in 1984.
PMID- 10185618
TI - Big changes at Oxford. Rosier outlook gives troubled HMO maneuvering room.
PMID- 10185619
TI - In it for the long haul? Stock market losses test hospitals' risk tolerance.
PMID- 10185620
TI - Salary/career survey: hospitals. Duties are expanding, but are salaries keeping
up?
PMID- 10185621
TI - HCFA proposes outpatient prospective payment plan.
PMID- 10185622
TI - Salary/career survey: ASCs (ambulatory surgery centers). Pay hikes higher for ASC
managers.
PMID- 10185623
TI - Salary/career survey. Many hats of OR director make role more demanding.
PMID- 10185624
TI - Is nursing losing voice in redesign?
PMID- 10185625
TI - Use your power with device makers.
PMID- 10185626
TI - OR Manager of Year is 'player coach'.
PMID- 10185627
TI - World watches Internet heart surgery.
PMID- 10185628
TI - Sacred cow survey. Survey finds progress on outdated OR rituals.
PMID- 10185629
TI - Sacred cow survey. ORs relaxing policies on nail polish.
PMID- 10185630
TI - Agitation about home-laundered scrubs.
PMID- 10185631
TI - Automating instrument management.
PMID- 10185632
TI - Software for instrument management.
PMID- 10185633
TI - AORN seeking a common language.
PMID- 10185634
TI - NIC, NOC, and NANDA in the perioperative record.
PMID- 10185636
TI - OR on wheels moves into high gear.
PMID- 10185635
TI - Medical errors: root cause analysis.
PMID- 10185637
TI - Year 2000 bug delays outpatient PPS.
PMID- 10185638
TI - Can physicians lead other physicians into the future?
AB - This article reflects upon some of the dynamics that prevent physicians from
successfully engaging change. Physicians are enculturated to the competitive and
hierarchical, and to value personal autonomy. These traits promote distrust and
inhibit the formation of collaborative relationships. At this time of growing
complexity, when most other industries are developing styles of work based on
teamwork, worker empowerment, cross training, and information sharing, physicians
cling to the metaphor of the ship's captain, a lone decision-marker and
authoritarian possessor of grand knowledge. And yet, in order to lead, physicians
need to learn to work differently and nurture a more collaborative approach. The
author's blueprint for change includes: Stop trying to manage consensus; commit
to measured accountability; think systemically; don't make the mistake of
thinking that people will follow because you are right; and, most importantly,
create relationships based on shared purpose and principles.
PMID- 10185639
TI - Which way to the frontier? Physician executives talk about the future.
AB - The author interviewed trustees, senior managers, and physicians at Moses Cone
Health System in Greensboro, North Carolina, Legacy Health System in Portland,
Oregon, and Henry Ford Health System in Detroit, Michigan. These three successful
health care systems bracket the national market in size, geography, and managed
care penetration. The comments of physicians are presented here, drawn from the
book, Designing 21st Century Health Care: Leadership in Hospitals and Healthcare
Systems. What emerges most clearly from their comments is the enormity of the
task ahead. There is wide-spread agreement that substantial improvements in the
quality and cost of care are possible, an encouraging stream of anecdotes and
ideas about how to proceed, but a lack of consensus on critical components of how
to organize practices and promote effective care.
PMID- 10185641
TI - The next step for physician executives?
AB - The next step for career growth for many physician executives will be the top
leadership role in a health care organization. The availability of such positions
for physicians has been limited in the past but could very well open in the
future. As physicians, administrators, and boards begin to trust each other more
and form meaningful partnerships, the potential for physician CEOs increases. In
1997, the Physician Executive Management Center conducted surveys of physicians
serving in CEO roles in hospitals and group practices throughout the country. We
compared the results with earlier surveys we had conducted since 1986. This
article reports the significant findings of these surveys on areas such as
employment contracts, job duties, skills and talents, and remuneration.
PMID- 10185640
TI - The new management team.
AB - There is no better place to instill the necessary sense of cooperation and
collaboration than the top. If top management, both physician and nonphysician,
can establish a suitable working relationship, and communicate both the necessity
for and success of the relationship throughout the organization, breakdowns in
cooperation and collaboration are far less likely to occur. Shared responsibility
and decision-making at the upper levels can be a laboratory for their use in
other organizational locations. The partnership between clinical and
administrative leadership is more important now than ever before. Medical group
practices are an ideal setting for testing a new form of shared management that
will help to rid organizations of the confrontational and adversarial attitudes
that have too long characterized relationships among managers and clinicians in
our health care organizations and institutions.
PMID- 10185642
TI - Management competencies required in ambulatory care settings.
AB - A study was conducted to identify the most important competencies physician
executives in medical groups and other ambulatory settings will need to have in
the next five years. The specific job skills, knowledge, and abilities (SKA) that
physician executives will need to acquire these competencies were also explored.
The Delphi techniques were used to analyze responses from two surveys from
members of the American College of Medical Practice Executives. The most
important competencies were grouped into 13 management domains, each with
specific SKAs. "Managing health care resources to create quality and value" and
"fundamentals of business and finance" were rated as the most important
competencies. The most frequently rated SKA was the "ability to build and
maintain credibility and trust."
PMID- 10185643
TI - Effects of role variables on job satisfaction.
AB - This study examines the effects of role variables on job satisfaction among
physician and non-physician executives in hospital settings. Positive
relationships were found for both groups between role variables and job
satisfaction. The results indicate that role variables have a significant effect
on stress, job satisfaction, and organizational commitment in the physician
executive and the non-physician health care executive. On a theoretical level,
this research allowed for an extended test of role theory, specifically as it
applies to the management of health care. The implications of these findings for
role theory and the physician executive are discussed. Since this study is of an
exploratory nature, it offers new insights into the field of health care
management, and the physician's role as the executive.
PMID- 10185644
TI - The cost of poor quality: an opportunity of enormous proportions.
AB - In all organizations, the state of finance is routinely reported in sublime
detail for study and action. And yet, anywhere from 20 to 50 percent of the
monies involved in that report are never identified as unnecessary and
nonproductive. These monies, referred to as the Cost of Waste (COW), are the
result of actions that have been taken or must be taken because quality is not
served--inappropriate actions are being performed or appropriate actions are not
being performed right the first time, every time. Proactively determining,
reporting, and monitoring the COW brings a degree of objectivity to the quality
management process and provides a powerful internal driver for performance
improvement. A 10 step Cost of Waste system is proposed.
PMID- 10185645
TI - Physician credentialing. A centralized verification system.
AB - The current system for credentialing physicians in the U.S. is staggeringly
redundant, prone to error, and expensive. The process for establishing a recent
graduate's practice can involve an average of five applications to have
privileges at several hospitals and HMOs. A centralized verification system needs
to be developed to streamline this process. The amount of information that would
have to be stored for all physicians in the country would be immense. However,
the technology currently exists to store such information on a much grander
scale. Credit unions, banks, and insurance companies utilize such computer
systems effectively and with reasonable confidentiality.
PMID- 10185646
TI - Doing or being?
AB - The founder of Aikido, Morihei Ueshiba, would occasionally distill the essence of
the art into three simple shapes--a circle, a square, and a triangle. These are
three basic ways of dealing with what's coming at you. The square is the
simplest. It is about, essentially, doing nothing. The saying here is from the
old spiritual: "I shall not be moved." You meet the challenge head on. The
triangle is about forward motion--attack, cutting right to the heart of what is
coming at you, or cutting right past it to the space beyond. The circle is often
the most interesting space. The circle is not about standing ground or cutting
through. The circle is about dancing with whatever is headed your way. The real
danger lies in being stuck in any one mode--perpetually intransigent, always
flailing away in attack mode, or forever slip-sliding through one dance step
after another. It is only when our response is embodied in who we are that we
will have the power truly to lead other people.
PMID- 10185647
TI - Is high touch finally here?
AB - Can anyone single-handedly create a caring environment without adding hours to
his or her work week? As turnover continues to rise, it's worth considering.
Techniques managers say have worked for them are suggested, including: Monitor
workloads; celebrate successes; make niceness an expectation; mentor; offer
training as often as possible; stamp out problems before they go public; consider
offering flexible hours and extended leaves for all; and introduce yeast to keep
people stimulated. Will these strategies--all of which may not work for you-
fatten your bonus this year? Probably not, unless top management is monitoring
retention and doing occasional exit interviews. However, one of the byproducts is
that employees don't stop with each other. They begin to treat patients better,
something neither bribery nor threats may produce.
PMID- 10185648
TI - Servant leadership.
AB - As corporations are eagerly pursuing reengineering and reorganization, leadership
functions are changing to champion these efforts. Traditionally, organizations
have had a "top-down" management approach, however, there is a gradual shift to
other leadership models. Servant leadership is being successfully implemented in
many settings. Servant leadership, first popularized by Robert Greenleaf in 1970,
puts serving others as the number one priority. Ten characteristics of a servant
leader include: Listening, empathy, healing, awareness, persuasion,
conceptualization, foresight, stewardship, commitment to the growth of people,
and building community. Both servant leadership and the chaos theory have in
common the central tenet of relationships. Since America is now approximately 80
percent a "service-economy," servant leadership can greatly benefit the
individual employees, as well as help to facilitate the organization's pursuit of
its changing strategic plans.
PMID- 10185649
TI - What turns you on and off?
AB - When you are exploring your career and where you are headed, it is helpful to
consider what aspects of your job turn you on, and of course, those that don't.
Energizers are activities that excite and invigorate you or people who lift your
heart and inspire you. De-energizers are activities or people who drain you, drag
you down, depress you. Make lists of those things that energize and de-energize
you either at work or in other situations. Try hard to do something to
incorporate or change at least the first five on each list and see if you feel
more job and life satisfaction. Responses from 30 participants of a recent Career
Choices program are provided to help you get started.
PMID- 10185650
TI - Professionalism is judged by appearances ... like it or not.
AB - Exploring the larger subject of executive professionalism should include the
whole range of behavior issues that affect others' perceptions of you. In this
competitive environment, with limited time to manage relationships, physician
executives must take control of all aspects affecting their credibility and
communications. This is not to suggest that you become the stereotyped, air
brushed news anchor, all style and little substance, but that you create a total
package, one in which the "inside" and the "outside" of your presentation are
complementary. Focus your attention on how well you have developed these factors
as a physician executive: Appearance; demeanor; professionalism; and integrity.
To create a "total package," it is helpful to consider the following
recommendations: Write "commercials" for yourself and your organization; use
every interaction as a selling opportunity; make every context a platform; don't
hide from criticism--seek it out; and use every opportunity that comes your way
to listen.
PMID- 10185652
TI - Information technology: opening the box.
AB - If you thought managed care was a tough nut to crack, wait until you have to
start making decisions about your organization's information technology (IT).
Information systems are complex and expensive, they can take years to implement,
and, once installed, they need costly and regular upgrades. But for a
contemporary clinical organization to function, this technology is as essential
as power and water. For many years, information technology was seen as a black
box, impenetrable and beyond real understanding. If done with knowledge and care,
however, cracking the box opens up possibilities, not ruin.
PMID- 10185651
TI - The tobacco wars: back to the states.
AB - With the United States Senate's failure to pass comprehensive tobacco
legislation, the fight to recover public health costs from big tobacco shifts
back to the states. The question for those working to reduce youth smoking rates
is whether that battle can be accomplished at the state level.
PMID- 10185653
TI - Compliance crunch.
AB - The U.S. Department of Justice is showing no mercy in its campaign against what
it calls "fraud and abuse" in Medicare billing. Here's what you can do to keep
the wolf from coming through your door.
PMID- 10185654
TI - Oy vay, Y2K! The millenium bug may be the most pervasive infection your hospital
has ever battled.
PMID- 10185655
TI - What's your liability?
PMID- 10185656
TI - Layers of leadership. The challenges of collaborative governance.
AB - If your goal is the health of a population, you can't do it alone. But working
with partners requires special skills, not the least which is the ability to
share control and put trust in others--in other words, collaborative governance.
Here's some guidance for getting to this next level.
PMID- 10185657
TI - Cover me. How far does trustee responsibility for expanded health care coverage
go?
PMID- 10185658
TI - CCNs and PSOs: connecting the dots.
PMID- 10185659
TI - Building a better trustee.
PMID- 10185660
TI - Bridging gaps between private and public health.
PMID- 10185661
TI - A new definition of philanthropy.
PMID- 10185662
TI - Wanted: progressive leaders for a new era.
PMID- 10185663
TI - Governing the living health system.
PMID- 10185664
TI - When suitors come to call.
PMID- 10185665
TI - The pride of the Yankees. A Maine hospital's willingness to barter gives new life
to an old idea.
AB - Many people in rural Maine are long on pride but short on health insurance.
Thanks to an innovative barter program at Franklin Memorial Hospital, they can
keep their pride, get the care they need, and offer their talents to the hospital
in exchange for services. It's a win-win situation for everyone.
PMID- 10185666
TI - Heritage of health: Charleston's lessons for the nation. Interview by Shari
Mycek.
PMID- 10185667
TI - Search for new organs leads to the barnyard. Animals may help ease transplant
shortage.
PMID- 10185668
TI - Burying Freud and praising him. Ambivalence over psychoanalysis fuels new
examinations of his legacy.
PMID- 10185669
TI - AIDS claims fewer victims. But infection rates still remain steady.
PMID- 10185670
TI - Volunteers: the backbone of health care change.
PMID- 10185671
TI - 85 ways to recognize volunteers.
PMID- 10185672
TI - Bring the world to your door: tapping international volunteers.
PMID- 10185673
TI - Abandoned to the street. How illness and "the system" cost a mother her daughter.
PMID- 10185674
TI - On a mission from God. Nuns' healing spirit tamed the frontier.
PMID- 10185675
TI - Sharing the wealth. Philanthropies strongly influenced American health care's
evolution.
PMID- 10185676
TI - No place to go. Crack cocaine and HIV have created a generation of babies who
call the hospital home.
PMID- 10185677
TI - Have puppets, will travel. How a magical puppet theater cheers young patients.
PMID- 10185678
TI - Chaplains want to define who is qualified to do God's work.
PMID- 10185680
TI - Culture, communication and service quality in health care administration: a tale
of two hospitals.
AB - This paper reports the results of a qualitative cross-case analysis of two medium
sized Australian general hospitals moving to a new era of service quality
management. The analysis was based on a model of perceptions of organisational
culture, communication and quality of patient care. Results showed that the
prevailing culture at the two hospitals was quite different, but there was
consistency in the relationships between the study variables. In particular,
perceptions of culture and communication had an impact on perceptions of quality
of care. The results are discussed within the context of previously reported
findings.
PMID- 10185679
TI - Developing a funding model for an after-hours primary medical care service in a
rural town.
AB - The study described in this paper aimed to determine a funding model for an after
hours primary medical care service in the rural town of Moe, a socioeconomically
disadvantaged area of Victoria suffering the rigours of industry restructuring
and privatisation. It has 12.5 equivalent full-time general practitioners
servicing 21,966 persons. A break-even analysis of the financial viability
compared the expected costs of providing the service with the anticipated income.
A mixed funding model is recommended. This would incorporate a general
practitioner incentive scheme and State Government underwriting of infrastructure
and basic non-medical staffing costs during the business development phase to
supplement the income from the Health Insurance Commission.
PMID- 10185681
TI - Is there equity in emergency medical care? Waiting times and walk-outs in South
Western Sydney hospital emergency departments.
AB - This study explores the association between selected socioeconomic
characteristics of emergency patients with waiting times in emergency departments
and walk-outs (those who did not wait for treatment) in South Western Sydney Area
Health Service hospital emergency departments. Bivariate and multivariate
analyses indicated that waiting times to see a doctor and walk-out rates varied
by age, sex, country of birth, insurance status, socioeconomic status, severity
of patient illness and day of arrival. Patients who were female, from a non
English-speaking background, self-referred, uninsured and those from lower
socioeconomic status showed significantly longer waiting times than others.
Patients who left emergency departments without treatment showed higher waiting
times from arrival to triage than other groups. This applied across socioeconomic
categories. These findings indicate that prolonged waiting times for triage,
which occur at the busiest periods, may be one of the main indicators for
patients leaving emergency departments without treatment. The study also
demonstrates variability in waiting times, which could possibly be partly
addressed by more standardised triage policies, but may be influenced by other
non-clinical factors, which require further investigation.
PMID- 10185682
TI - Hospital outcomes management: the Care Continuum and Health Outcomes Project.
AB - The Care Continuum and Health Outcomes Project is part of a national initiative
to build an outcomes management approach in health care. This paper examines the
baseline performance of the study. In 1995-96, 7154 Australian Capital Territory
hospital inpatients were selected to take part in a five-wave survey over six
months. In addition to the survey, the project involved the unit record linkage
of routine data collections. A total of 5668 people (79%) agreed to participate
in the survey, with 85% of these people agreeing to release their Medicare data.
There were significant variations in participation rates between hospitals and
wards. Factors contributing to these variations included patient socioeconomic
status, disease type and illness severity. In conclusion, the success in
establishing the project indicates that it is possible to conduct a broad
scientific study within the health system, and that there are strong implications
that ongoing scientific evaluations can be embedded within routine clinical
practice.
PMID- 10185683
TI - Applying a health outcomes approach in a health service unit.
AB - An explicit focus on health outcomes has the potential to improve health if
applied at the local level. However, clinical services require clear and
practical support in the measurement and analysis of health outcome indicators.
This paper suggests 12 steps for departments or services to take in promoting an
outcomes orientation, based on our experiences in the Central Sydney Area Health
Service. These include determining commitment at the service level, setting up a
working group, specifying service consumers, their health problems and
intervention processes, specifying desired health changes, consulting the
literature and peers, identifying existing resources, pilot-testing and refining
outcome measures, collecting data and responding to sub-optimal results with
evidence-based interventions. The paper also reviews common criticisms of the
health outcomes approach and key issues which have arisen in the course of
applying these steps at the local level.
PMID- 10185684
TI - Strategic planning in hospitals in two Australian states: an exploratory study of
its practice using planning documentation.
AB - Hospitals are under pressure to respond to new challenges and competition. Many
hospitals have used strategic planning to respond to these environmental changes.
This exploratory study examines the extent of strategic planning in hospitals in
two Australian States, New South Wales and Victoria, using a sample survey. Based
on planning documentation, the study indicated that 47% of the hospitals surveyed
did not have a strategic or business plan. A significant difference was found in
the comprehensiveness of the plans between the two States. Plans from Victorian
hospitals had more documented evidence of external/internal analysis, competitor
orientation and customer orientation compared with plans from New South Wales
hospitals. The paper discusses the limitations of the study and directions for
future research.
PMID- 10185685
TI - The development of a mental health service patient information management system.
AB - In this paper we describe the development of the Mental Health-Patient
Information Management System (MH-PIMS), which is an information management
system designed for use in a modern, primarily community-based, mental health
service. MH-PIMS is a computerised database which was designed by clinicians and
is supported by a case management system and complementary patient record set
together called the Assessment and Care Evaluation (ACE) system. The paper also
describes the ACE system. MH-PIMS can generate patient reports of use to case
managers and teams in managing their caseloads and is of use to senior clinicians
and service managers for audit and strategic planning purposes.
PMID- 10185686
TI - What precipitates deliberate self-harm? A cognitive behavioural formulation of
attempted suicide presentations at an inner city hospital.
AB - OBJECTIVE: To develop a working model that provides an understanding of the
process of deliberate self-harm and a framework for psychological intervention in
an emergency department setting. METHOD: A retrospective clinical audit of a
consecutive series of 51 deliberate self-harm patients referred to the liaison
psychiatry service by the emergency department of an inner city hospital.
RESULTS: Patient characteristics were diverse. The age range was 17-92 years,
with 79% between 15 and 35 years. Most were single and unemployed and the
majority had a psychiatric disorder. Characteristically, there was at least one
immediate stressor and intoxication immediately before the attempt. CONCLUSIONS:
The diversity of deliberate self-harm patients requires strategic intervention in
a setting such as the emergency department. The working model for intervention
presented here may be transferable to other settings such as general practice or
community mental health centres using an educational and skills development
approach with ongoing supervision.
PMID- 10185687
TI - The Allied Health BONE (Best Orthopaedic New Enterprise) team: an
interdisciplinary approach to orthopaedic early discharge and admission
prevention.
AB - This paper presents the conceptual framework, activities and outcomes of the
Allied Health BONE (Best Orthopaedic New Enterprise) Team, an early discharge
incentive at the Gold Coast Hospital. The clinical team of a physiotherapist,
occupational therapist and social worker provided services within an
interdisciplinary model of care with the aim of reducing the length of stay of
acute adult orthopaedic patients. The team provided intervention in the
community, the accident and emergency department, pre-admission clinic and
orthopaedic wards to patients with hip and knee replacements, back pain and upper
femoral fractures. This paper reports data from the first six months of the
project, demonstrating success in improving the continuity of care provided to
orthopaedic patients and reducing the length of stay in target groups by 24%.
PMID- 10185688
TI - Building a learning organisation in a child and adolescent mental health service.
AB - In recent business literature, the model of the learning organisation has been
proposed as a solution to the problem of continually changing environments and
increasing consumer expectations of maximum quality and value for money. The
model seems highly appropriate for health services, which are staffed by educated
professional staff who must become more adaptive and concerned with improving
consumer outcomes. This case study describes how the principles of learning
organisations have been applied to the design of a new structure and the creation
of a learning culture within a mental health service for children and
adolescents.
PMID- 10185690
TI - Asthma mortality in Australia, 1980-1996.
PMID- 10185689
TI - The second national hospital costing study: background, results and implications.
AB - The costing of hospital outputs, and especially of acute admitted patients
categorised by DRG, has been the focus of considerable attention in the last
decade. Many individual hospitals now routinely estimate the costs of their main
products, several State and Territory health authorities undertake periodic multi
site studies, and there have been a few one-off national studies. This paper
summarises the methods and results of the most recent national study, which
measured costs at a sample of public and private hospitals around Australia for
the 1996-97 financial year. We briefly describe the main results and note some
implications.
PMID- 10185691
TI - Funding arrangements for telehealth: encouraging efficiency rather than
proliferation.
AB - The use of telehealth as a basis for delivering health services is growing across
Australia, and there is clear potential for these technologies to address some of
the enduring issues of access and costs of service delivery. However, appropriate
incentives must be created to encourage clinicians and managers to evaluate the
true opportunity costs and benefits of delivering services in this way against
the relevant alternative. This paper examines how different funding arrangements
might encourage or discourage efficient use of telehealth.
PMID- 10185692
TI - Towards culturally competent health care: language use of bilingual staff.
AB - The presence of diverse language skills within health staff provides
opportunities to better meet the needs of a multicultural population. A cross
sectional survey of all staff within the South Western Sydney Area Health Service
was undertaken to compare language skills with population needs and examine the
context of language use. Thirty-one per cent of staff (n = 964) were bilingual or
multilingual, with the predominant languages spoken being Tagalog (Filipino),
Cantonese, Hindi, Spanish, Vietnamese and Italian. Thirty-seven per cent of
bilingual staff used their language skills at least weekly, predominantly in
situations of simple conversation and giving directions. Bilingual staff are a
valuable resource for the organisation and the presence of a similar overall
proportion of bilingual and bicultural staff may engender tolerance and
adaptability in providing care to a diverse population. However, supply does not
directly match community demand. This mismatch will continue unless recruitment
is focused towards identified language groups. The high proportion of staff who
rarely used their language skills (37%) may be due to lack of opportunity or
limited need, and suggests that further research needs to examine service models
that locate bilingual workers close to client need. This study takes a crucial
first step towards realising equitable and culturally appropriate care utilising
the principles of productive diversity.
PMID- 10185693
TI - Elective admission policies in New South Wales public hospitals.
AB - OBJECTIVE: To assess the existence and content of elective admission policies in
New South Wales acute public hospitals. METHODS: A questionnaire was sent to
managers of all acute public hospitals (n = 76). Copies of elective admission
policies were sought from respondents. Results were analysed with EpiInfo 5.01b
and policy content by thematic analysis. RESULTS: Survey response was 91%
(69/76). Policies existed in 71% (49/69) of hospitals. Of these, 96% (47/49)
disseminated their policy, with 23% (11/47) disseminating it at least annually,
41% (19/47) only when updated, and 32% (15/47) infrequently, with one policy
being new (2%) and one hospital not stating its frequency (2%). Policy compliance
was assessed in 86% (42/49) of hospitals and guidelines reviewed periodically in
92% (45/49) of hospitals. Twenty per cent (10/49) of the policies had been
developed since a departmental instruction of May 1994. Of the 20 acute hospitals
with no policy, 75% (15/20) were rural and 85% (17/20) thought they should have a
policy. Analysis of policy content revealed emphases on resource availability and
clinical need as determinants of elective admission, an institutional rather than
a patient focus, and a high level of senior nurse manager involvement in
admission decisions in rural hospitals. CONCLUSIONS: Despite a specific
departmental instruction, nearly one-third of hospitals still had no admission
policy 18 months later. This could be indicative of miscommunication between
hospitals and NSW Health or perceived irrelevance of department guidelines by
hospital managers. Existing policies were mostly institutionally focused and
dominated by perceived resource limitations. NSW Health might consider other
medico-social factors and manager involvement in future policy development.
PMID- 10185695
TI - A review of hospital medical record audits: implications for funding and
training.
AB - This paper summarises the findings of coding audits in seven hospitals and one re
audit conducted by the Health Department of Western Australia. The accuracy of
the coding in the first audits, as measured by differences in AN-DRG assignment,
varied from 83% to 93%. The accuracy of the coding in the re-audited hospital
increased by 6% to 94.5%. The major coding problems related to incorrect
abstraction of information from the medical record, inaccurate code assignment,
non-application of the Australian Coding Standards, or poor documentation. On
average, these coding problems resulted in a loss of nearly $400,000 per hospital
per year in the surveyed hospitals.
PMID- 10185694
TI - Protecting patient confidentiality in hospitals.
AB - As new methods of electronic data storage and distribution appear in hospitals,
new challenges in protecting confidentiality have emerged. At the same time,
demands for 'seamless' care and the desire to share information between
clinicians are motivating hospitals to relax barriers to the transfer of patient
information. Increasing numbers of users at multiple sites compound the
difficulty of ensuring information systems security. Hospital policy may demand
that requests by patients to restrict the distribution of personal information be
respected, while existing electronic systems are not able to deliver on this
promise. Compliance with the Information Privacy Principles of the Commonwealth
Privacy Act 1988 and the Australian Standard 4400-1995 'Personal privacy
protection in health care information systems' will provide a useful framework
for managing these challenges. However, their implementation will require some
forethought.
PMID- 10185696
TI - Blood-borne virus-related discrimination in dental services.
AB - While the risk of infection through occupational exposure to blood-borne viruses
is a major concern of dental health care workers, the National HIV/AIDS Strategy
and many health, AIDS and discrimination-related agencies have identified
discrimination related to HIV/AIDS as a priority area for action. In 1995 the
Commonwealth Department of Health and Family Services selected the School of
Medical Education at the University of New South Wales to conduct a national
project to reduce discrimination related to blood-borne viruses within dental
services (Godwin, Meihubers & Rotem 1997). This paper provides an overview of the
study and its major findings. The study focused on quality of care issues which
may cause or manifest discrimination. Key stakeholders were invited to review
policies, procedures, organisational arrangements and other systemic issues which
influence the quality of oral health services to populations within selected
geographical regions.
PMID- 10185697
TI - Got it? Share it. No managed care organization is too small for an extranet to
pay back big.
PMID- 10185698
TI - Thinking out-of-the-box. HITS (Healthcare Information and Technology Systems)
Award demonstrates the power of ingenuity.
PMID- 10185699
TI - From airports to care centers. Transferring information technology to support
patient care reengineering.
AB - PROBLEM: To improve communication among caregivers about the status of patients
under their care. SOLUTION: Replacing manual white boards with electronic bed
boards/inpatient databases, similar to airport display technology. RESULTS:
Improved data quality from having patient data displayed in a standardized manner
across care centers. KEYS TO SUCCESS: "We used a process redesign team, which
focused on specific issues related to the processes used in providing patient
care."
PMID- 10185700
TI - Know the code. Federal E and M coding requirements deliver a double whammy to
unprepared practices.
PMID- 10185701
TI - Promises of things to come. Object technology products will benefit from
certification, collaboration and HL7.
PMID- 10185702
TI - Quantum leap. Interview by Terry Monahan.
PMID- 10185703
TI - Hop on the bandwidth wagon. Telemedicine pioneers reveal what works, what doesn't
and why.
PMID- 10185704
TI - Love, love? Hardly, as ActiveX and CORBA volley for leadership.
PMID- 10185705
TI - Secret societies.
PMID- 10185706
TI - Who's growing CIOs?
PMID- 10185707
TI - Diagnosing doctors. Four types of physicians require four approaches to promote
clinical computing acceptance.
PMID- 10185709
TI - Where are our maintenance trade people coming from?
PMID- 10185708
TI - Integrating PACS power.
AB - While the technology side of PACS is strong, it's the way you implement your PACS
-and especially the way you integrate your PACS with your hospital and radiology
information system--that makes all the difference.
PMID- 10185710
TI - Research labs present unique health and safety issues.
PMID- 10185711
TI - Vital organs: hospitals partner with organ procurement organizations to comply
with regulations, increase donations.
PMID- 10185712
TI - To the rescue! Birmingham hospitals donate life-saving 12-lead EKG machines to
rescue units.
PMID- 10185713
TI - Montgomery's Baptist Health takes home AHA's "Living the Vision" Award.
PMID- 10185714
TI - Eagar to serve. Bessemer Carraway Medical Center administrator takes over as
AlaHA Chairman.
PMID- 10185715
TI - Get well soon.
PMID- 10185716
TI - Closer to home.
AB - As stated earlier, there are about 20 hospital-based health and fitness centers
in the state of Alabama. Here is a closer look at some of the Alabama hospitals
that have decided to tackle this type of venture.
PMID- 10185718
TI - An evolving continuous quality improvement role for managed care: a behavioral
healthcare perspective.
AB - Managed care's initial continuous quality improvement impact may have been
comparable to the sentinel, or Hawthorne, effect. Managed behavioral healthcare's
CQI role can be compared with that of the clinical navigator. The clinical
navigator attempts to develop a consensus with the patient on what is the
clinical destination, and must choose a route to travel that is the best approach
to reach the destination (i.e., a focused treatment plan). In addition, the
clinical navigator tries to find the most efficient mode of travel--or, the least
restrictive, least intrusive site of care from where the patient can receive
treatment. Essential clinical tasks or expectations in the clinical assessment
are also outlined, and the concept of knowledge coupling is introduced to
accommodate the unique, individual issues of the patient. The emphasis of managed
care today is shifting to further accentuate a CQI, outcomes-based approach.
PMID- 10185717
TI - Ensuring quality care: what do you get for your money?
AB - In the rush to produce balanced scorecards and outcomes measures, managed care
organizations must recognize the need to better assess the clinical competencies
of their contracted skilled nursing facilities. Health plan quality management
staffs, although composed of gifted professionals, generally do not have
sufficient skilled nursing facility (SNF)-related experience or knowledge to
support evaluation and qualification of these providers. The successfully
implemented Altman-Conrad (A-C) SNF quality management process objectively
measures and monitors managed care contracted services provided by SNFs. The A-C
process requires a health plan's quality management/utilization management staff
to engage in a team-based educational endeavor. This effort is designed to
generate measurable outcomes specific to the health plan's needs. The proven
benefits of the process include improved member services, greater member
satisfaction, more productive days for SNFs, more effective discharges, and the
generation of a win-win relationship between the health plan and its contract
providers.
PMID- 10185720
TI - Using a key function approach to performance improvement: a case study.
AB - Assisting organizations with performance improvement planning is among the most
important, challenging, and potentially rewarding responsibilities of the quality
management professional. NorthCrest Medical Center, a 100-bed not-for-profit
community hospital, developed a long-term vision for quality which was then
supported through a unique model of performance improvement based on important
functions. The resulting key function framework has helped the organization
prepare for two successful Joint Commission surveys, relocate to a new facility,
and survive in today's rapidly changing environment.
PMID- 10185719
TI - The facility site review process for MCOs: clinical versus nonclinical reviewers.
AB - Managed care organizations (MCOs) conduct provider facility site reviews to
promote quality standards in office practice operations and to comply with such
regulating agencies as the Joint Commission, various payers, and the Michigan
Department of Community Health and statutes such as the Michigan Occupational
Safety and Health Act. The results of the facility site reviews are incorporated
into the credentialing and recredentialing decision processes for individual
practitioners and provider organizations. This study sought to compare the
facility site reviews conducted by nurse reviewers who were experienced in
quality management of managed care with site reviews conducted by nonclinical
staff. In 9 of the 22 sites, the nurse reviewers' scores more accurately
represented the primary care physicians' compliance with existing standards and
regulations than did those reported by the nonclinical reviewers. This study
supports the recommendation that facility site reviews be conducted by nurses
experienced in the quality management of managed care.
PMID- 10185721
TI - The strategic role of health informatics in integrated delivery systems.
AB - Having accurate measures and high-quality health information is critically
important for all providers today. Integrated delivery systems are faced with
increasing demands for numerous redundant, sometimes conflicting, performance
measurement and reporting data from managed care customers, regulators, and
accreditors. When implemented independently within each organizational subunit,
these measurement systems are costly and difficult to manage. Centralization of
all measurement services can maximize the productivity of the costly resources
required to deliver them and can achieve efficiencies, cost savings, and a better
balance between internal and external resources while collecting information that
is of a higher quality for managerial and clinical decision making.
PMID- 10185722
TI - Joint Commission preparation in a large academic medical center: a framework for
success.
AB - A large urban university medical center used a unique set of strategies in
preparation for its triennial survey conducted by the Joint Commission on
Accreditation of Healthcare Organizations. Although the medical center had
experienced many Joint Commission surveys, this particular survey was the first
to include associated physician offices in multiple diverse settings. To address
these challenges, the hospital developed a structure and process that engaged all
levels of staff and ensured a successful survey outcome.
PMID- 10185723
TI - Blood-borne diseases in 1998: an overview.
PMID- 10185724
TI - Getting organized: are physician unions really the answer?
PMID- 10185725
TI - One surgeon's experience on Capitol Hill: an interview with Karen Guice, MD, MPP,
FACS. Interview by Christopher Gallagher.
PMID- 10185726
TI - Ultrasound for the general surgeon: an ACS initiative.
PMID- 10185727
TI - Payments for assistants at surgery.
PMID- 10185728
TI - Sinai Hospital: reworking the emergency department for efficiency, quality, and
service.
PMID- 10185729
TI - Do you need a health information security officer?
PMID- 10185730
TI - National survey. Today's hospitals: on the precipice?
PMID- 10185731
TI - Language of finance spoken here.
PMID- 10185732
TI - The big squeeze. Job market may be a lemon--but for some there are sweeter times
ahead.
PMID- 10185733
TI - Now you see it. Spot hidden costs in shipping and handling.
PMID- 10185734
TI - In for the overhaul. Process redesign hurts--but pays off.
PMID- 10185735
TI - Tame the telecom beast.
PMID- 10185736
TI - Nest eggs: handle with care.
PMID- 10185737
TI - Tooling around. Make standardization work for you.
PMID- 10185738
TI - Transplant tribulation. The government wants a new system for doling out donated
organs. Oh, what a ruckus it's causing!
PMID- 10185739
TI - End-of-life care.
PMID- 10185741
TI - Advance directive statement. Good Samaritan Health System, Phoenix.
PMID- 10185740
TI - Translating good will into good words.
AB - Physicians often are uncomfortable talking with patients about unfavorable
diagnoses and advance care planning; patients, in turn, require reassurance,
uncomplicated language and promises that their wishes will be respected. Steven
Levy, M.D., discusses the steps providers should take in talking with patients at
the end of life.
PMID- 10185742
TI - New healthcare quality coalition promises best practices.
AB - An initiative spearheaded by the Institute for Healthcare Improvement and the
National Coalition on Health Care has announced plans to develop and disseminate
best practice guidelines for providers. Organizations that cut overuse, underuse
and misuse of services could reduce costs by 30%, proponents claim.
PMID- 10185743
TI - Improving care at the end of life.
AB - Americans are more likely to die slowly of chronic disease than from a rapid,
fatal illness or injury, but the healthcare delivery system rarely fully
accommodates patients' needs at the end of life. Organizations working to change
the way patients spend their final days are looking first at pain control,
continuity of care, advance planning and ways to make the experience meaningful
for both patients and family.
PMID- 10185744
TI - Measuring health plans' performance in chronic care.
AB - To accurately assess a health plan's ability to care for its chronically ill
patients, accreditors must look not only at disease-specific criteria but at the
organization's ability to provide and manage care for its entire population,
according to Cary Sennett of the National Committee for Quality Assurance.
PMID- 10185745
TI - AAHP identifies best practices for breast cancer.
AB - In the first in a new series of reports on women's health, the American
Association of Health Plans recognizes four health plans that have added case
management, patient education and psychosocial resources for breast cancer
patients.
PMID- 10185746
TI - Making the most of data for disease management.
AB - Managed care organizations have a wealth of administrative, claims and clinical
data available to them--data that could pinpoint patients who could benefit from
cost-effective disease management programs. Health plans that have such efforts
offer advice on how to home in on the best data.
PMID- 10185747
TI - Recommendations for adult immunization. National Coalition for Adult
Immunization.
PMID- 10185748
TI - Creating cost-effective flu shot programs.
PMID- 10185749
TI - Great immunizations.
PMID- 10185750
TI - Health risks of overseas business travel.
PMID- 10185751
TI - Looking to the future.
PMID- 10185752
TI - Data watch. Impact of select vaccine-preventable diseases in the U.S.
PMID- 10185753
TI - It pays to immunize adults.
PMID- 10185754
TI - Healthcare paradoxes in the new millennium.
PMID- 10185755
TI - Managing "value" on the front line.
PMID- 10185756
TI - What do employers mean by "value?" Part I: How do purchasers think?
PMID- 10185757
TI - Leadership in the UK NHS: where are we now?
AB - The introduction of changes to the UK National Health Service from the 1980s
onwards, coupled with recognition that successful improvement to health and
health services places greater pressure on developing good inter-personal and
inter-organisational relationships, underlines the need for greater leadership of
health services in the future. Argues that insufficient attention has been paid
to the development of external leadership, the growing importance of which is
emphasised by the most recent proposals for change to health services from the
1997 Labour government. Comparisons of managerial life between the public and
private sectors are made and surveys of NHS managerial work, carried out over a
number of years, seem to have produced similar conclusions. Finally a paradigm
shift is called for in the leadership of health services in the future if the
impact of the external environment is to be managed more effectively and no
longer to be seen as a constraint on public sector managerial activity.
PMID- 10185758
TI - Between physician and manager: new co-operation models in Dutch hospitals.
AB - Analyses the way hospital organisation models handle the relationship between
medical specialists and hospital management. All models that have been developed
during the last ten years seek to integrate the medical specialists in the
hospital organisation by formally subordinating them to the hospital management.
However, recently a new model has come to the fore--the "co-makership"--in which
the hospital management and the medical specialists are assigned a position
alongside each other.
PMID- 10185759
TI - Stakeholders' views of management development as a cultural change process in the
Health Service.
AB - Illustrates the failure of a competence-based management development programme in
a hospital trust to achieve organisational objectives. The approach and content
of the management development programme is resisted by participants despite the
facilitators drawing on management theory to legitimate it. The question posed in
this paper, building on an earlier study by Holman and Hall (1996), is whether
the generic approach of competence-based management development is appropriate in
the UK NHS. The theoretical inspiration for the research is what may be termed a
"processual" or "contextualist" approach which is clearly influenced by
"negotiated order" literature.
PMID- 10185760
TI - The importance of the pharmaceutical industry to the UK economy.
AB - The objective of this paper is to indicate the importance of the pharmaceutical
industry to the UK economy. Data on various aspects of the industry are presented
and examined. As background information a collection of policies and pressures on
the pharmaceutical environment are identified and discussed. The evidence shows
what the UK economy stands to lose if it loses its pharmaceutical industrial
base. Concludes that policy and pressure affecting drug products also affect drug
companies; some of this is not realised when drug product policies are
considered; the people of the UK will still need drugs whether or not the UK has
a pharmaceutical base; the UK economy stands to lose a significant amount of
benefits if it loses its pharmaceutical industrial base.
PMID- 10185761
TI - The logic of job-sharing in the provision and delivery of health care.
AB - By definition the practice of job-sharing starts from the premiss that there is a
full-time job to be shared by those who want to balance their work with other
commitments. In a public sector institution, such as the National Health Service
(NHS), where most employees are female, it seems logical to believe that a job
sharing policy would be able to promote equal opportunities, to increase employee
job satisfaction and to reduce labour costs. Hence, this paper attempts to
discuss the advantages and disadvantages of having a job-sharing policy, and to
analyse the reasons for the limited number of job-sharers in the NHS despite the
apparent benefits of job-sharing to both the employees and the employer. This
study was carried out in 15 NHS Trusts in northern England and Scotland, by the
use of questionnaires and interviews, and found that most NHS managers did not
see the practice of job-sharing as a major cost-saving opportunity or as a
working pattern that would enhance employee satisfaction and commitment. They saw
job-sharing as just a routine equal opportunities request which did not deserve
such managerial attention or long-term strategic thinking. It is argued in this
paper that job-sharing is a potentially useful option against a background of
demographic and other social and economic changes which require the development
and use of long-term strategic policies. Therefore, it is concluded that, in the
NHS, there is a need for a more active and creative approach to job-sharing,
rather than the reactive and passive approach that has dominated the practice so
far.
PMID- 10185762
TI - Role of the consultant obstetrician in the delivery suite.
AB - The role of consultant obstetricians is under considerable debate. This has
particularly focused on the role of consultants in intrapartum care. The article
explores the role of the consultant in delivery suite from the view point of a
consultant, a clinical director, a training programme director and a chief
executive. These viewpoints determine a range of common themes which mean the
duties of consultants over their career lifecycle need to be addressed; the need
to expand consultant posts; and the tensions which inevitably occur. The authors
believe these need to be addressed because of the need to ensure consultant roles
in delivery suite are developed as a key part of seeing quality improvement.
PMID- 10185763
TI - Towards development of professional management in Indian hospitals.
AB - Hospitals consume the largest share of government health resources, yet, until
recently, they have not been a focus of health policy and research in developing
countries, where the resources are in negative proportion to the demands placed
on services of health care institutions, and where the possibility of resources
being increased in the short run is very remote, the only hope for the increase
in the effectiveness of the health care system being the effective management of
hospitals. A professional administrator with multidisciplinary training would
ensure the optimal use of resources. We live in the age of perfection at all
levels. Hence, professional training is the basic requirement for the personnel
to function effectively in a hospital. Professional training is required to be
imparted by the institutions specialised in professional training. Professional
management has an immense scope and a bright future market on account of the
increasing demand for specialised and quality health care. Better management or
lack of it will determine the future of health service. This paper focuses on
development of management and the requirement for professional administrators in
India.
PMID- 10185764
TI - Strategic marketing and clinical management in health care: a possible way
forward.
AB - This article examines and comments on the role of clinical directors in the NHS
(UK), with specific reference to the relevance of a strategic marketing emphasis.
It utilises qualitative methodologies to collect data from stakeholders--in
particular, clinical directors and other managers--from two NHS trust hospitals.
It examines the extent to which a marketing approach is applicable to clinical
managers working in these two hospitals. It utilises a conceptual framework
devised by Kottler and Andreason, to highlight whether a marketing approach is,
in fact, utilised by these managers. It suggests that a strategic marketing
approach (based upon relationships), remains relevant to clinical management,
notwithstanding recent changes in government policy.
PMID- 10185765
TI - Health care reform.
PMID- 10185766
TI - Developing "out of hours" primary health care. Some key qualitative factors in
service selection and evaluation by patients in the UK.
AB - The issue of "out of hours" provision of primary care services by family doctors
has excited particularly marked debate in the UK. This article considers the
implications for this debate of results from a project designed to elicit the
views of users of out of hours primary care provision. Focus groups were used to
gauge definitions of "out of hours" services, factors governing the use of some
services rather than others and influences on the evaluation of different
options. The centrality accorded by patients to the social dimensions of a more
"traditional" relationship with family doctors was central to the selection and
evaluation of alternative provision. Any significant initiative in the
reconfiguration of local health care services might thus be regarded as much a
social enterprise as a technical challenge based on the most equitable and
efficient application of resources.
PMID- 10185767
TI - Managing evidence-based health care: a diagnostic framework.
AB - This paper proposes a diagnostic framework useful to Trust managers who are faced
with the task of devising and implementing strategies for improvements in
clinical effectiveness, and is based on a recent study incorporating clinicians,
managers, and professional staff in four NHS Trusts in the North Thames Region.
The gap framework is inspired by the gap model developed by Zeithaml, Parasuraman
and Berry from their research into service quality and incorporates Dave
Sackett's schema as well as a personal competency profile needed for the practice
of evidence based health-care (EBHC). The paper highlights the four
organisational and personal failures (gaps) which contribute to the fifth gap,
namely the discrepancy between clinically relevant research evidence and its
implementation in health care. To close the gaps, Trusts need to set the goal and
tackle the cultural, organisational, attitudinal and more material aspects such
as investment in the information infrastructure, education and training of
doctors. Doctors need to go through a process from awareness to action
facilitated through a combination of personal and organisational incentives and
rewards as well as training in the requisite skills. Researchers should take
steps to improve the quality of the evidence and its accessibility and purchasers
should reinforce the use of EBHC by withdrawing funding for care which has proved
to be ineffective, inappropriate or inferior.
PMID- 10185768
TI - The development of clinical management at an NHS Trust hospital. A case study
example.
AB - The article examines and comments on the development of clinical management at an
NHS hospital Trust. It utilises a qualitative case study methodology to collect
data from key stakeholders at this Trust. The data suggest some of the reasons
why doctors may be receptive or non-receptive to the notion of clinical
management. It recommends that attention is focused on the specialty context as a
key factor in influencing the development of clinical management. It also
suggests there may be other important factors, for example: training, the role of
change agents; structure of clinical directorates; and individual factors such as
cognition, attitudes and motivation.
PMID- 10185769
TI - Developing new professional partnerships with acute Trusts and general
practitioners.
AB - The development of locality commissioning models combined with demographic,
therapeutic and service changes are driving new professional relationships
between general practitioners and acute Trusts. To ensure a Trust releases its
strategy in this environment, stakeholders must understand the benefits to be
gained from these new levels of relationships. A review of the literature is
undertaken and the conditions for successful partnerships between acute Trusts
and general practitioners defined. The article determines that for acute Trusts
it will mean an examination of core competences combined with a drive to "review"
their organisations.
PMID- 10185770
TI - A decision analytic approach to commissioning ambulance cardiac services.
AB - The paper discusses how a decision analytic framework has been used by an English
health authority in relation to the commissioning of ambulance cardiac services.
Strategies for the management by ambulance personnel of victims of cardiac arrest
and persons with acute chest pain of cardiac origin were modelled in a decision
event tree, and a bibliographic database established. The international research
literature prior to 1997 was searched in order to derive probability values for
the tree. However, after checking whether the subgroupings of results in the
papers were in accordance with the variables in the tree, the number of useful
papers on acute chest pain was found to be only two. In the almost complete
absence of information--even from small observational studies--on the management
of the great majority of patients with cardiac symptoms transported by ambulance,
the local ambulance service and the main providers of hospital services in the
district are now collaborating in field studies of cardiac care in order to
improve the inputs into the model.
PMID- 10185771
TI - An approach to setting priorities in health planning.
AB - This paper describes work undertaken in Pakistan within a project to strengthen
the health planning system, aimed at improving the capacity of the planning cells
to identify priorities and develop broad strategic guidelines. The work starts
from the premise that identification of priorities requires two stages. In the
first stage, problems must be structured and defined in a way that is accepted by
all major stakeholders in the planning process. In the second stage, a
transparent process of decision making must exist which will provide the means
for the planning group to establish priorities and time-scales. The tools chosen
in this instance were selected in relation to the characteristics of the local
environment, and the paper describes these.
PMID- 10185772
TI - Promote customer perceptions of value: the ladder of effects.
AB - Seven categories of measures are typically used by managed care organizations
(MCOs) in monitoring and evaluating the effects of demand improvement efforts on
their own performance: (1) member participation in specific initiatives, (2)
changes in member mind-states, (3) member behavior, (4) member health status, (5)
member service use, and (6) health care expenditures, as well as (7) a variety of
value-adding side effects. These same seven can be even more useful to MCOs in
monitoring and demonstrating the value they are delivering to their customers.
The potential for the MCOs to extend the use of these parameters and gain added
value for themselves thereby are discussed, and specific examples are offered to
illustrate this potential.
PMID- 10185773
TI - The role of branding in health care.
AB - Branding has been successfully practiced by consumer packaged goods companies for
decades. But only recently have managed health care organizations begun to
embrace the concept, and hence, few well developed brands exist. For health care
organizations, the rewards of branding can be great as it provides an opportunity
to truly assess the needs of their members, develop capabilities to meet those
needs, and more effectively communicate the ability to meet those needs. A
summary of seven steps to building a strong brand is also included.
PMID- 10185774
TI - Branding: a promise with a solid base.
AB - Over the past several decades, branding as a process of differentiating one
company, product, or service from another has been central to the business
efforts of a wide range of commercial enterprises. In more recent years, branding
has become part of the lexicon of health care, where its function is accepted and
its potential benefits desired. Much of the emphasis regarding brand building,
however, is in the area of marketing. Although communications and their inherent
promises remain an essential component in brand development for health care
providers and managed care companies, the ultimate value of branding lies in its
integration into an organization's operational structure and strategies.
PMID- 10185775
TI - Consumerism as a branding opportunity.
AB - Managing a customer portfolio at the individual level is the most difficult and
most promising endeavor. An individual level consumer portfolio does not mean
creating marketing materials and advertising campaigns customized for every
member of your health plan. What it does mean is developing segmentation models
based on consumer preferences extracted directly from your members, not
socioeconomic or other demographic models. The most important information to
extract is perceptions on how much and what kind of value members want from the
organization.
PMID- 10185776
TI - Health care consumerism, the information explosion, and branding: why 'tis better
to be the cowboy than the cow.
AB - Managed care faces a rising consumerist attitude, fueled by the aging of the baby
boom generation. If health plans and other managed care companies are to position
themselves positively in their markets' minds, they must embrace fundamental
marketing principles, beginning with a sound understanding of the feelings,
attitudes, and expectations of those they serve. Absent such customer knowledge,
a "tag team" comparising market forces and public policy will pin down the
industry. However, with careful research and sound planning, there are
opportunities for managed care companies to wrest control of their brands and
position themselves for health care in the next millenium.
PMID- 10185777
TI - Beyond traditional behavioral health care.
PMID- 10185778
TI - Managing the utilization of managed care (health care reform II).
PMID- 10185779
TI - Health plan accreditation: NCQA, JCAHO, or both?
AB - Currently the National Committee for Quality Assurance (NCQA) and the Joint
Commission on the Accreditation of Healthcare Organizations (the Joint
Commission) accredit managed care organizations (MCOs), but is competition in the
market for plan accreditation beneficial or counterproductive? This paper
presents the results from two surveys that were administered to a group of large
public and private purchasers, and representatives from the American Association
of Health Plans and the Centers for Disease Control, who attended the Lovelace
Health System (LHS) "Accreditation Experience" program. The LHS program was
designed to inform purchasers about the NCQA and Joint Commission accreditation
processes. The surveys captured purchaser views about the advantages and
disadvantages of both accreditation processes, the value of accreditation, and
the use of plan performance measures.
PMID- 10185780
TI - In California, Medi-Cal managed care is superior to Medi-Cal fee-for-service.
AB - This is a comparative analysis of California's "experiment" in Medi-Cal managed
care. It compares managed care to fee-for-service in the area of quality. In
March 1993, the California State Department of Health Services issued a State
Strategic Plan for Medi-Cal Managed Care. The goal: to transfer the delivery of
care for the majority of the state's Medi-Cal population from a predominantly fee
for-service payment system to capitated managed care. The state of California has
steadily increased its commitment to the large-scale expansion of managed care
within the Medi-Cal Program in order to improve beneficiaries' access to quality
preventative and primary health care while acting as a prudent purchaser of
services. This study examines one Local Initiative--Inland Empire Health Plan-
created as a not-for-profit, joint powers, public entity by Riverside and San
Bernardino counties, California.
PMID- 10185781
TI - Does managed care work?
PMID- 10185782
TI - Ranking the health plans. Newsweek's annual survey gauges how well HMOs are
serving their members.
PMID- 10185783
TI - Having it all. Americans want the impossible when it comes to health care.
PMID- 10185784
TI - Reinventing Medicare. The government readies its new 'Choice' plan--but will
seniors understand it?
PMID- 10185785
TI - Quality in health care. Now more centre-stage and with a strong Australian
identity.
PMID- 10185786
TI - A brief introduction to network-based coding systems.
PMID- 10185787
TI - The art and science of developing and applying competency standards.
PMID- 10185788
TI - Medical record education in Australia--from 1949 to 1999.
PMID- 10185789
TI - University entry scores as a predictor of academic performance in a health
information management program.
AB - The university entry scores for school leavers admitted to the first year of the
Bachelor of Applied Science (Health Information Management) degree at the
University of Sydney in 1996 were examined to determine whether the Tertiary
Entrance Rank (TER) was a good predictor of academic performance, as measured by
grade point average (GPA). The study also examined Higher School Certificate
(HSC) results in English and mathematics, and preference selection for the health
information management (HIM) course to determine whether any of these had
predictive validity. The results showed that TER, HSC English and mathematics
scores and preference for the course were all poor predictors of academic
performance in the student's first year. Low TER was not associated with low GPA
and low scores in English and mathematics were not associated with low GPA. There
was no significant difference between the performance of those students who
listed the HIM course as their first preference and those who did not. These
results suggest that there may be no need to establish a minimum entry level for
admission to the HIM course, or for prerequisites in English and mathematics. It
may be that multiple criteria are required to predict academic success in this
course.
PMID- 10185790
TI - Lifelong learning. Why professionals must have the desire for and the capacity to
continue learning throughout life.
AB - This paper will outline the theoretical constructs pertaining to lifelong
learning, adult education, continuing professional development and the learning
society. The need for all professionals to have highly developed learning skills
in a society racing with change is evident. Pressures placed on health
information managers to continue their learning beyond graduation are many and
varied. Continuing professional education is one avenue that enables health
information managers to continue their learning beyond graduation. Attributes of
a typical lifelong learner are included in this paper to enable readers to self
assess their capacity for continued learning and their desire to undertake it.
The paper concludes with a list of strategies for learners to enhance their
lifelong learning skills. The role that educators can play in developing lifelong
learning competence in students and graduates is also outlined.
PMID- 10185791
TI - Royal Adelaide Hospital: EQuIP (Evaluation and Quality Improvement Program)
evaluation.
PMID- 10185792
TI - Experiencing EQuIP (Evaluation and Quality Improvement Program) at Flinders
Medical Centre.
PMID- 10185793
TI - The introduction of ICD-10-AM in health information management education at the
University of Sydney.
PMID- 10185794
TI - Interviewing.
PMID- 10185795
TI - The White Paper: a focus on clinical coding.
PMID- 10185796
TI - NHS Number update (taken from the NHS executive briefing documents).
PMID- 10185797
TI - What is SGML (Standard Generalised Markup Language)?
PMID- 10185798
TI - Organisation of clinical coding in Australia.
PMID- 10185799
TI - Medicare program: request for public comments on implementation of risk adjusted
payment for the Medicare+Choice program and announcement of public meeting--HCFA.
Solicitation of comments; announcement of meeting.
AB - This notice solicits further public comments on issues related to the
implementation of risk adjusted payment of Medicare+Choice organizations. Section
1853(a)(3) of the Social Security Act (the Act) requires the Secretary to
implement a risk adjustment methodology that accounts for variation in per capita
costs based on health status and demographic factors for payments no later than
January 1, 2000. The methodology is to apply uniformly to all Medicare+Choice
plans. This notice outlines our proposed approach to implementing risk adjusted
payment. In order to carry out risk adjustment, section 1853(a)(3) of the Act
also requires Medicare+Choice organizations, as well as other organizations with
risk sharing contracts, to submit encounter data. Inpatient hospital data are
required for discharges on or after July 1, 1997. Other data, as the Secretary
deems necessary, may be required beginning July 1998. The Medicare+Choice interim
final rule published on June 26, 1998 (63 FR 34968) describes the general process
for the collection of encounter data. We also included a schedule for the
collection of additional encounter data. Physician, outpatient hospital, skilled
nursing facility, and home health data will be collected no earlier than October
1, 1999, and all other data we deem necessary no earlier than October 1, 2000.
Given any start date, comprehensive risk adjustment will be made about three
years after the year of initial collection of outpatient hospital and physician
encounter data. Comments on the process for encounter data collection are
requested in that interim final rule. We intend to consider comments received in
response to this solicitation as we develop the final methodology for
implementation of risk adjustment. This notice also informs the public of a
meeting on September 17, 1998, to discuss risk adjustment and the collection of
encounter data. The meeting will be held at the Health Care Financing
Administration headquarters, located at 7500 Security Boulevard, Baltimore, MD,
beginning at 8:30 a.m. Additional materials on the risk adjustment model will be
available on or after October 15, 1998, and may be requested in writing from
Chapin Wilson, Health Care Financing Administration, Department of Health and
Human Services, 200 Independence Avenue, S. W., Room 435-H, Washington, DC 20201.
PMID- 10185800
TI - Medicare program; prospective payment system for hospital outpatient services-
HCFA. Proposed rule.
AB - As required by sections 4521, 4522, and 4523 of the Balanced Budget Act of 1997,
this proposed rule would eliminate the formula-driven overpayment for certain
outpatient hospital services, extend reductions in payment for costs of hospital
outpatient services, and establish in regulations a prospective payment system
for hospital outpatient services (and for Medicare Part B services furnished to
inpatients who have no Part A coverage). The prospective payment system would
simplify our current payment system and apply to all hospitals, including those
that are excluded from the inpatient prospective payment system. The Balanced
Budget Act provides for implementation of the prospective payment system
effective January 1, 1999, but delays application of the system to cancer
hospitals until January 1, 2000. The hospital outpatient prospective payment
system would also apply to partial hospitalization services furnished by
community mental health centers. Although the statutory effective date for the
outpatient prospective payment system is January 1, 1999, implementation of the
new system will have to be delayed because of year 2000 systems concerns. The
demands on intermediary bill processing systems and HCFA internal systems to
become compliant for the year 2000 preclude making the major systems changes that
are required to implement the prospective payment system. The outpatient
prospective payment system will be implemented for all hospitals and community
mental health centers as soon as possible after January 1, 2000, and a notice of
the anticipated implementation date will be published in the Federal Register at
least 90 days in advance. This document also proposes new requirements for
provider departments and provider-based entities. These proposed changes, as
revised based on our consideration of public comments, will be effective 30 days
after publication of a final rule. This proposed rule would also implement
section 9343(c) of the Omnibus Budget Reconciliation Act of 1986, which prohibits
Medicare payment for nonphysician services furnished to a hospital outpatient by
a provider or supplier other than a hospital, unless the services are furnished
under an arrangement with the hospital. This section also authorizes the
Department of Health and Human Services' Office of Inspector General to impose a
civil money penalty, not to exceed $10,000, against any individual or entity who
knowingly and willfully presents a bill for nonphysician or other bundled
services not provided directly or under such an arrangement. This proposed rule
also addresses the requirements for designating certain entities as provider
based or as a department of a hospital.
PMID- 10185801
TI - Medicare program; revisions to payment policies under the physician fee schedule
for calendar year 1999; correction--HCFA. Correction of proposed rule.
AB - This document corrects technical errors that appeared in the proposed rule
published in the Federal Register on June 5, 1998, entitled "Medicare Program;
Revisions to Payment Policies Under the Physician Fee Schedule for Calendar Year
1999."
PMID- 10185802
TI - Solicitation of information and recommendations for developing OIG compliance
program guidance for certain Medicare+Choice organizations--OIG, HHS. Notice.
AB - This Federal Register notice seeks the input and recommendations of interested
parties into the OIG's development of a compliance program guidance for
Medicare+Choice organizations that offer coordinated care plans (M+CO/CCPs). The
OIG has previously developed compliance program guidances for hospitals, clinical
laboratories and home health agencies in order to provide clear and meaningful
guidance to those segments of the health care industry. In an effort to provide
similar guidance to certain M+C organizations, we are soliciting comments,
recommendations and other suggestions from concerned parties and organizations on
how best to develop compliance program guidance and reduce fraud and abuse within
M+CO/CCPs.
PMID- 10185803
TI - Amended economic impact analysis of final rule requiring use of labeling on
natural rubber containing devices--FDA. Final rule; amended economic analysis
statement.
AB - The Food and Drug Administration (FDA) is issuing an amended economic analysis
statement relating to a final rule that published in the Federal Register of
September 30, 1997 (62 FR 51021), requiring labeling statements concerning the
presence of natural rubber latex in medical devices. This rule was issued in
response to numerous reports of severe allergic reactions and deaths related to a
wide range of medical devices containing natural rubber. The final rule becomes
effective on September 30, 1998. In order to allow further comment on the
economic impact of the September 30, 1997, final rule, FDA published in the
Federal Register of June 1, 1998, an amended economic impact statement, including
an amended initial regulatory flexibility analysis (IRFA) that it prepared under
the Regulatory Flexibility Act (RFA), as amended by the Small Business Regulatory
Enforcement and Fairness Act (SBREFA). After considering comments submitted in
response to the June 1, 1998, amended economic analysis statement, FDA is issuing
the amended final economic impact statement, including an amended final
regulatory flexibility analysis.
PMID- 10185804
TI - Administrative practices and procedures; internal agency review of decisions-
FDA. Direct final rule; withdrawal.
AB - The Food and Drug Administration (FDA) published in the Federal Register of June
16, 1998 (63 FR 32733), a direct final rule to implement the new Dispute
Resolution provision of the Federal Food, Drug, and Cosmetic Act, as amended by
the Food and Drug Administration Modernization Act of 1997 (FDAMA). The comment
period closed on August 31, 1998. FDA is withdrawing the direct final rule
because the agency received significant adverse comment.
PMID- 10185805
TI - Administrative practices and procedures; internal agency review of decisions;
companion document to direct final rule; correction--FDA. Proposed rule;
correction.
AB - The Food and Drug Administration (FDA) is correcting a proposed rule that
appeared in the Federal Register of June 16, 1998 (63 FR 32772). The document
proposed to amend the FDA regulations governing the review of agency decisions by
inserting a statement that sponsors, applicants, or manufacturers of drugs
(including biologics) or devices may request review of a scientific controversy
by an appropriate scientific advisory panel, or an advisory committee. The
document was published with an error. This document corrects that error.
PMID- 10185806
TI - Methodology for determining whether an increase in a state's child poverty rate
is the result of the TANF program--Administration for Children and Families, HHS.
Proposed rule.
AB - The Administration for Children and Families is proposing a methodology to
determine the child poverty rate in each State. If a State experiences an
increase in its child poverty rate of 5 percent or more as a result of its
Temporary Assistance for Needy Families (TANF) program, the State must submit and
implement a corrective action plan. This requirement is a part of the new welfare
reform block grant program enacted in 1996.
PMID- 10185807
TI - Medicare and Medicaid programs; announcement of additional applications from
hospitals requesting waivers for organ procurement service area--HCFA.
AB - This notice announces two additional applications that HCFA has received from
hospitals requesting waivers from entering into agreements with their designated
organ procurement organizations (OPOs) in accordance with section 1138(a)(2) of
the Social Security Act. It supplements notices published in the Federal Register
on January 19, 1996, May 17, 1996, November 8, 1996, April 21, 1997, and
September 17, 1997, that announced hospital waiver requests received by us. This
notice requests comments from OPOs and the general public for our consideration
in determining whether these waivers should be granted.
PMID- 10185808
TI - Claims based on exposure to ionizing radiation (prostate cancer and any other
cancer)--VA. Final rule.
AB - This document amends the Department of Veterans Affairs (VA) adjudication
regulations concerning compensation for diseases claimed to be the result of
exposure to ionizing radiation. This amendment implements a decision by the
Secretary of Veterans Affairs that, based on all evidence currently available to
him, prostate cancer and any other cancers may be induced by ionizing radiation.
The intended effect of this action is to relieve veterans, or their survivors,
seeking benefits under the provisions of the Veterans' Dioxin and Radiation
Exposure Compensation Standards Act of the burden of having to submit evidence
that a veteran's prostate cancer or any other cancer may have been induced by
ionizing radiation.
PMID- 10185809
TI - International Conference on Harmonisation; guidance on viral safety evaluation of
biotechnology products derived from cell lines of human or animal origin;
availability--FDA. Notice.
AB - The Food and Drug Administration (FDA) is publishing a guidance entitled "Q5A
Viral Safety Evaluation of Biotechnology Products Derived From Cell Lines of
Human or Animal Origin." The guidance was prepared under the auspices of the
International Conference on Harmonisation of Technical Requirements for
Registration of Pharmaceuticals for Human Use (ICH). The guidance describes the
testing and evaluation of the viral safety of biotechnology products derived from
characterized cell lines of human or animal origin, and outlines data that should
be submitted in marketing applications.
PMID- 10185810
TI - Amendment to examination and investigation sample requirements--FDA. Direct final
rule.
AB - The Food and Drug Administration (FDA) is amending its regulations regarding the
collection of twice the quantity of food, drug, or cosmetic estimated to be
sufficient for analysis. This action increases the dollar amount that FDA will
consider to determine whether to routinely collect a reserve sample of a food,
drug, or cosmetic product in addition to the quantity sufficient for analysis.
Experience has demonstrated that the current dollar amount does not adequately
cover the cost of most quantities sufficient for analysis plus reserve samples.
This direct final rule is part of FDA's continuing effort to achieve the
objectives of the President's "Reinventing Government" initiative, and is
intended to reduce the burden of unnecessary regulations on food, drugs, and
cosmetics without diminishing the protection of the public health. Elsewhere in
this issue of the Federal Register, FDA is publishing a companion proposed rule
under FDA's usual procedures for notice and comment to provide a procedural
framework to finalize the rule in the event the agency receives any significant
adverse comment and withdraws this direct final rule.
PMID- 10185811
TI - General administrative rulings and decisions; amendment to the examination and
investigation sample requirements; companion document to direct final rule--FDA.
Proposed rule.
AB - The Food and Drug Administration (FDA) is proposing to amend its regulations
regarding the collection of twice the quantity of food, drug, or cosmetic
estimated to be sufficient for analysis. This action increases the dollar amount
that FDA will consider to determine whether to routinely collect a reserve sample
of a food, drug, or cosmetic product in addition to the quantity sufficient for
analysis. Experience has demonstrated that the current dollar amount does not
adequately cover the cost of most quantities sufficient for analysis plus reserve
samples. This proposed rule is a companion to the direct final rule published
elsewhere in this issue of the Federal Register. This action is part of FDA's
continuing effort to achieve the objectives of the President's "Reinventing
Government" initiative, and it is intended to reduce the burden of unnecessary
regulations on food, drugs, and cosmetics without diminishing the protection of
the public health.
PMID- 10185812
TI - Medical devices; establishment registration and device listing for manufacturers
and distributors of devices--FDA. Direct final rule.
AB - The Food and Drug Administration (FDA) is amending certain regulations governing
establishment registration and device listing by domestic distributors. These
amendments are being made to implement revisions to the Federal Food, Drug, and
Cosmetic Act (the act), as amended by the Food and Drug Modernization Act of 1997
(FDAMA). Elsewhere in this issue of the Federal Register, FDA is publishing a
companion proposed rule, under FDA's usual procedures for notice and comment, to
provide a procedural framework to finalize the rule in the event the agency
receives any significant adverse comment and withdraws the direct final rule.
PMID- 10185813
TI - Medical devices; establishment registration and device listing for manufacturers
and distributors of devices; companion to direct final rule--FDA. Proposed rule.
AB - The Food and Drug Administration (FDA) is proposing to amend certain regulations
governing establishment registration and device listing by domestic distributors.
This proposed rule is a companion document to the direct final rule published
elsewhere in this issue of the Federal Register. These amendments are being made
to implement revisions to the Federal Food, Drug, and Cosmetic Act (the act) as
amended by the Food and Drug Administration Modernization Act of 1997 (FDAMA).
This companion proposed rule is being issued under FDAMA and the act as amended.
PMID- 10185814
TI - Guidance for industry: donor screening for antibodies to HTLV-II; availability-
FDA. Notice.
AB - The Food and Drug Administration (FDA) is announcing the availability of a
document entitled "Guidance for Industry: Donor Screening for Antibodies to HTLV
II." The guidance document provides information regarding human T-lymphotrophic
virus type II (HTLV-II) screening tests for Whole Blood and blood components.
This guidance document is a further effort of FDA to help ensure a safe blood
supply for the United States of America (U.S.).
PMID- 10185815
TI - Medicaid program; Medicaid managed care--HCFA. Proposed rule.
AB - This proposed rule would amend the Medicaid regulations to allow the States
greater flexibility by giving them the option to require Medicaid recipients to
enroll in managed care entities without obtaining waivers. These revisions, which
are authorized by the Balanced Budget Act of 1997, would establish new
beneficiary protections in areas such as quality assurance, grievance rights, and
coverage of emergency services. They would eliminate certain requirements viewed
by State agencies as impediments to the growth of managed care programs, such as
the enrollment composition requirement, the right to disenroll without cause at
any time, and the prohibition against enrollee cost-sharing. They would also
permit State agencies to amend their State plans to require enrollment in managed
care organizations subject to certain conditions, including limits on whose
enrollment can be mandated, and a requirement for beneficiary choice. In
addition, this rule would extend most of these new requirements to prepaid health
plans.
PMID- 10185816
TI - Medicare program; establishment of the Medicare+Choice program--HCFA. Correction
of interim final rule with comment period.
AB - On June 26, 1998, we published in the Federal Register, at 63 FR 34,968, an
interim final rule with comment period that explains and implements those
provisions of the Balanced Budget Act of 1997 that established the
Medicare+Choice program. This notice corrects errors made in the June 26
document.
PMID- 10185817
TI - Medicare program; changes to the hospital inpatient prospective payment systems
and fiscal year 1999 rates; corrections--HCFA. Final rule; correction notice.
AB - In the July 31, 1998 issue of the Federal Register (63 FR 40,594), we published a
final rule revising the Medicare hospital inpatient prospective payment systems
for operating costs and capital related costs to implement applicable statutory
requirements, including the Balanced Budget Act of 1997 (BBA), as well as changes
arising from our continuing experience with the system. In addition, in the
addendum to that final rule, we announced the amounts and factors for determining
prospective payment rates for Medicare hospital inpatient services for operating
costs and capital-related costs applicable to discharges occurring on or after
October 1, 1998, and set forth rate-of-increases limits for hospitals and
hospital units excluded from the prospective payment systems. This document
corrects errors made in that document.
PMID- 10185818
TI - Medicare program; update of ratesetting methodology, payment rates, payment
policies, and the list of covered procedures for ambulatory surgical centers
effective October 1, 1998; reopening of comment period and delay in adoption of
the proposed rule as final--HCFA. Notice of reopening of comment period for
proposed rule and delay in adoption of provisions of the proposed rule as final.
AB - This notice reopens the comment period for a proposed rule affecting Medicare
payments to ambulatory surgical centers (ASCs) that was originally published in
the Federal Register on June 12, 1998 (63 FR 32290). This document gives notice
of a delay in the adoption of the provisions of the June 12, 1998 ASC proposed
rule as a final rule to be concurrent with the adoption as final of the hospital
outpatient prospective payment system (PPS) that is the subject of a proposed
rule published in the Federal Register on September 8, 1998 (63 FR 47551). In
addition this document confirms that the current ASC payment rates that are
effective for services furnished on or after October 1, 1998, will remain in
effect until rebased ASC rates and the provisions of the June 12, 1998 ASC
proposed rule are adopted as final to be concurrent with the adoption as final of
the Medicare hospital PPS.
PMID- 10185819
TI - Compatibility of wireless services with enhanced 911--FCC. Proposed rule.
AB - The Commission seeks additional comment in wireless Enhanced 911 (E911)
rulemaking proceeding with respect to an ex parte presentation filed by Ad Hoc
Alliance for Public Access to 911 (Alliance) on September 17, 1998. In its ex
parte filing and its accompanying engineering report, Alliance has presented an
approach under which the Commission would require that, if the signal from the
user's provider is "inadequate" at the time a 911 call is placed through the use
of an analog cellular handset, then the handset must have the capability to
select automatically the strongest available compatible channel of communications
for purpose of completing the 911 call. Additional comment is sought to assist
the Commission in determining whether to adopt the approach presented by the
Alliance in its September 17 ex parte filing. The effect of adopting the Alliance
approach would be to improve reliability of 911 services to wireless customers.
PMID- 10185820
TI - United States of America v. Medical Mutual of Ohio; proposed final judgment and
competitive impact statement--DoJ.
PMID- 10185821
TI - Solicitation of information and recommendations for developing OIG compliance
program guidance for certain Medicare+Choice organizations--OIG, HHS. Correction.
PMID- 10185822
TI - Medicare program; prospective payment system and consolidated billing for skilled
nursing facilities; correction--HCFA. Correction of interim final rule with
comment period.
AB - This document corrects technical errors that appeared in the interim final rule
with comment period published in the Federal Register on May 12, 1998 entitled
"Medicare Program; Prospective Payment System and Consolidated Billing for
Skilled Nursing Facilities."
PMID- 10185823
TI - Medicare program; hospice wage index--HCFA. Notice.
AB - This notice announces the annual update to the hospice wage index as required by
42 CFR 418,306(c). This update is effective October 1, 1998. The wage index is
used to reflect local differences in wage levels. The hospice wage index
methodology and values are based on recommendations of a negotiated rulemaking
advisory committee and were originally published in the Federal Register on
August 8, 1997. This update is the second year of a 3-year transition period. The
second transition year begins October 1, 1998 and ends September 30, 1999.
PMID- 10185824
TI - Failure by certain charitable organizations to meet certain qualification
requirements; taxes on excess benefit transactions--IRS. Correction to notice of
proposed rulemaking.
AB - This document contains a correction to REG-245256-94, which was published in the
Federal Register on Tuesday, August 4, 1998 (63 FR 41486), relating to the excise
taxes on excess benefit transactions.
PMID- 10185825
TI - Medical devices; 30-day notices and 135-day PMA supplement review--FDA. Final
rule.
AB - The Food and Drug Administration (FDA) is amending its regulations governing the
submission and review of premarket approval (PMA) supplements to provide for the
submission of a 30-day notice for modifications to manufacturing procedures or
methods of manufacture. Amendments are being made to implement revisions to the
Federal Food, Drug, and Cosmetic Act (the act) as amended by the Food and Drug
Administration Modernization Act of 1997 (FDAMA).
PMID- 10185826
TI - List of drug products that have been withdrawn or removed from the market for
reasons of safety or effectiveness--FDA. Proposed rule.
AB - The Food and Drug Administration (FDA) is proposing to amend its regulations to
include a list of drug products that may not be used for pharmacy compounding
pursuant to the exemptions under section 503A of the Federal Food, Drug, and
Cosmetic Act (the act) because they have had their approval withdrawn or were
removed from the market because the drug product or its components have been
found to be unsafe or not effective. The list has been compiled under the new
statutory requirements of the Food and Drug Administration Modernization Act of
1997 (Modernization Act).
PMID- 10185827
TI - Medicaid program; disproportionate share hospital payments-institutions for
mental disease--HCFA. Notice.
AB - This notice announces the Federal share disproportionate share hospital (DSH)
allotments for Federal fiscal years (FFYs) 1998 through 2002. This notice also
describes the methodology for calculating the Federal share DSH allotments for
FFY 2003 and thereafter, and announces the FFY 1998 and FFY 1999 limitations on
aggregate DSH payments States may make to institutions for mental disease (IMD)
and other mental health facilities. In addition, it clarifies the DSH reporting
requirements required by the Balanced Budget Act of 1997 (BBA '97).
PMID- 10185828
TI - Premerger notification: reporting and waiting period requirements--FTC. Notice of
adoption of formal interpretation and request for comments.
AB - The Premerger Notification Office ("PNO") of the Federal Trade Commission
("FTC"), with the concurrence of the Assistant Attorney General in charge of the
Antitrust Division of the Department of Justice ("DOJ"), is adopting a Formal
Interpretation of the Hart-Scott-Rodino Act, which requires certain persons
planning certain mergers, consolidations, or other acquisitions to report
information about the proposed transactions to the FTC and DOJ. The
Interpretation concerns the reportability of certain transactions involving a
Limited Liability Company ("LLC"), a relatively new form of entity authorized by
state statutes. Under the Interpretation, the formation of an LLC will be
reportable if it will unite two or more pre-existing businesses under common
control. Similarly, acquisitions of existing LLC membership interests will be
reportable if they would have the effect of uniting two or more pre-existing
businesses under common control.
PMID- 10185829
TI - Medical care collection or recovery--VA. Proposed rule.
AB - This document proposes to amend VA's medical regulations concerning collection or
recovery by VA for medical care or services provided or furnished to a veteran:
For a non-service connected disability for which the veteran is entitled to care
(or the payment of expenses of care) under a health-plan contract; For a non
service connected disability incurred incident to the veteran's employment and
covered under a worker's compensation law or plan that provides reimbursement or
indemnification for such care and services; or For a non-service connected
disability incurred as a result of a motor vehicle accident in a State that
requires automobile accident reparations insurance. Previously, by statute VA was
authorized to charge "reasonable costs" for such care or services. However,
amended statutory provisions now authorize VA to charge "reasonable charges."
Accordingly, this document proposes to establish methodology for charging
"reasonable charges" consistent with the statutory amendment. Under the proposal,
the charges billed using this methodology, as appropriate, would consist of
inpatient facility charges, skilled nursing facility/sub-acute inpatient facility
charges, outpatient facility charges, physician charges, and non-physician
provider charges. Reasonable charges for outpatient dental care and prescription
drugs not administered during treatment would continue to be billed using the
existing cost-based methodology. Pursuant to statutory authority, VA has the
right to recover or collect the charges from a third party to the extent that a
provider of the care or services would be eligible to receive payment therefor
from that third party if the care or services had not been furnished by a
department or agency of the United States. With respect to a third-party payer
liable under a health plan contract, consistent with the statutory authority, the
third-party payer would have the option of paying to the extent of its coverage,
either the billed charges or the amount the third-party payer demonstrates it
would pay for care or services furnished by providers other than entities of the
United States for the same care or services in the same geographic area. Using
the methodology in this proposed rule, the data for calculating actual amounts
for the various inpatient facility charges, skilled nursing facility/sub-acute
inpatient facility charges, outpatient facility charges, and physician charges at
individual VA facilities for the period August 1998 through September 1999 are
set forth in a companion document published in the "Notices" section of this
issue of the Federal Register. Also, under the proposal, the regulations would be
clarified to state specifically that billing methodology based on costs will
continue to be applied to establish charges for medical care furnished in error
or on tentative eligibility, furnished in a medical emergency, furnished to
certain beneficiaries of the Department of Defense or other Federal agencies,
furnished to pensioners of allied nations, and furnished to military retirees
with chronic disability.
PMID- 10185830
TI - Medical care collection or recovery--VA. Notice.
AB - In a companion document published in the "Proposed Rules" section of this issue
of the Federal Register, we proposed to amend VA's medical regulations concerning
collection or recovery by VA for medical care or services provided or furnished
to a veteran: (i) For a non-service connected disability for which the veteran is
entitled to care (or the payment of expenses of care) under a health-plan
contract; (ii) For a non-service connected disability incurred incident to the
veteran's employment and covered under a worker's compensation law or plan that
provides reimbursement or indemnification for such care and services; or (iii)
For a non-service connected disability incurred as a result of a motor vehicle
accident in a State that requires automobile accident reparations insurance. The
proposed rule includes methodology for establishing charges for VA medical care
or services. Using this methodology, information for calculating proposed charge
amounts at individual VA facilities for inpatient facility charges, skilled
nursing facility/sub-acute inpatient facility charges, outpatient facility
charges, and physician charges is set forth below. If this methodology were
adopted subsequently as a final rule, the applicable data in this document,
designed for the period August 1998 through September 1999, would be used for the
period from the effective date of the final rule through September 1999.
Accordingly, interested parties may wish to retain this document for future
reference.
PMID- 10185831
TI - Interim procedures for certain health care workers--INS. Interim rule with
request for comments.
AB - This interim rule, which has been drafted in consultation with the U.S.
Department of Health and Human Services (HHS), amends regulations of the
Immigration and Naturalization Service (Service or INS) in order to implement, on
a temporary basis, certain portions of section 343 of the Illegal Immigration
Reform and Immigrant Responsibility act of 1996 (IIRIRA) as they relate to
prospective immigrants. Section 343, which was codified at section 212(a)(5)(C)
of the Immigration and Nationality Act (Act or INA), provides that aliens coming
to the United States to perform labor in covered health care occupations (other
than as a physician) are inadmissible unless they present a certificate relating
to their education, qualifications, and English language proficiency. This
requirement is intended to ensure that aliens possess proficiency in the skills
that affect the provision of health care services in the United States. This rule
establishes a temporary mechanism to allow applicants for immigrant visas or
adjustment of status in the fields of nursing and occupational therapy of satisfy
the requirements of section 343 on a provisional basis. The Service expects to
publish a proposed rule in the near future which will implement in full the
provisions of section 343.
PMID- 10185832
TI - Medicare, Medicaid, and CLIA programs; extension of certain effective dates for
clinical laboratory requirements under CLIA--CDC, HCFA. Final rule with comment
period.
AB - This final rule extends certain effective dates for clinical laboratory
requirements in regulations published on February 28, 1992, and subsequently
revised December 6, 1994, and May 12, 1997, that implemented provisions of the
Clinical Laboratory Improvement Amendments of 1988 (CLIA). This rule extends the
phase-in date of the quality control requirements applicable to moderate and high
complexity tests and extends the date by which an individual with a doctoral
degree must possess board certification to qualify as a director of a laboratory
that performs high complexity testing. These effective dates are extended to
allow the Department additional time to issue revised quality control
requirements and to determine whether changes are needed in the qualification
requirements for individuals with doctoral degrees to serve as directors of
laboratories performing high complexity testing. These effective date extensions
do not reduce the current requirements for quality test performance.
PMID- 10185833
TI - Draft guidance for industry on developing medical imaging drugs and biologics;
availability--FDA. Availability of guidance.
AB - The Food and Drug Administration (FDA) is announcing the availability of a draft
guidance for industry entitled "Developing Medical Imaging Drugs and Biologics."
This draft guidance is intended to assist developers of drug and biological
products used for medical imaging, as well as radiopharmaceutical drugs used in
disease diagnosis, in planning and coordinating the clinical investigations of,
and submitting various types of applications for, such products. The draft
guidance also provides information on how the agency will interpret and apply
provisions in the proposed regulations for in vivo radiopharmaceuticals used for
diagnosis and monitoring, which published in the Federal Register of May 22, 1998
(63 FR 28301).
PMID- 10185835
TI - FDA Modernization Act of 1997: modifications to the list of recognized standards;
availability; withdrawal of draft guidance "Use of IEC 60601 standards; medical
electrical equipment"--FDA. Notice.
AB - The Food and Drug Administration (FDA) is announcing the publication of the
modifications to the list of standards that will be recognized for use in the
premarket review process and withdrawing its draft guidance entitled "Use of IEC
60601 Standards; Medical Electrical Equipment." This will assist manufacturers
who elect to declare conformity with consensus standards to meet all or part of
medical device review requirements.
PMID- 10185834
TI - Federal Employees Health Benefits Program improving carrier performance;
conforming changes--OPM. Final rule.
AB - The Office of Personnel Management (OPM) is issuing a final regulation that
implements OPM's initiative to ensure high quality customer service to its
enrollees in the Federal Employees Health Benefits (FEHB) Program by establishing
a performance evaluation program that will hold community-rated carriers
accountable for their performance. The regulation would enable OPM to better
manage carriers' performance in key contract areas, including customer service
measures, information and reporting requirements, and significant events that
might affect service to enrollees.
PMID- 10185836
TI - Cost of hospital and medical care treatment furnished by the United States;
certain rates regarding recovery from tortiously liable third persons--OMB.
PMID- 10185837
TI - Civilian Health and Medical Program of the Uniformed Services (CHAMPUS); TRICARE
prime balance billing--DoD. Final rule.
AB - This final rule establishes financial protections for TRICARE Prime enrollees in
limited circumstances when they receive covered services from a non-network
provider.
PMID- 10185838
TI - "Guidance for industry: current good manufacturing practice for blood and blood
components: (1). Quarantine and disposition of units from prior collections from
donors with repeatedly reactive screening test for antibody to hepatitis C virus
(anti-HCV); (2). Supplemental testing, and the notification of consignees and
blood recipients of donor test results for anti-HCV;" availability--FDA. Notice.
AB - The Food and Drug Administration (FDA) is announcing the availability of a
guidance document (dated September 1998) entitled "Guidance for Industry: Current
Good Manufacturing Practice for Blood and Blood Components: (1) Quarantine and
Disposition of Units From Prior Collections From Donors With Repeatedly Reactive
Screening Test for Antibody to Hepatitis C Virus (Anti-HCV); (2) Supplemental
Testing, and the Notification of Consignees and Blood Recipients of Donor Test
Results for Anti-HCV." The guidance document provides recommendations for donor
screening and supplemental testing for antibody to hepatitis C virus (HCV),
notification of consignees and quarantine of prior collections from a donor who
later tests repeatedly reactive for antibody to HCV, notification of recipients
of blood and blood components at increased risk for transmitting HCV.
PMID- 10185839
TI - Medicare program; inpatient hospital deductible and hospital and extended care
services coinsurance amounts for 1999--HCFA. Notice.
AB - This notice announces the inpatient hospital deductible and the hospital and
extended care services coinsurance amounts for services furnished in calendar
year 1999 under Medicare's hospital insurance program (Medicare Part A). The
Medicare statute specifies the formulae used to determine these amounts. The
inpatient hospital deductible will be $768. The daily coinsurance amounts will
be: (a) $192 for the 61st through 90th day of hospitalization in a benefit
period; (b) $384 for lifetime reserve days; and (c) $96 for the 21st through
100th day of extended care services in a skilled nursing facility in a benefit
period.
PMID- 10185840
TI - Medicare program; monthly actuarial rates and monthly supplementary medical
insurance premium rate beginning January 1, 1999--HCFA. Notice.
AB - As required by section 1839 of the Social Security Act, this notice announces the
monthly actuarial rates for aged (age 65 or over) and disabled (under age 65)
enrollees in the Medicare Supplementary Medical Insurance (SMI) program for 1999.
It also announces the monthly SMI premium rate to be paid by all enrollees during
1999. The monthly actuarial rates for 1999 are $92.30 for aged enrollees and
$103.00 for disabled enrollees. The monthly SMI premium rate for 1999 is $45.50.
(The 1998 premium rate was $43.80). The 1999 Part B premium is not equal to 50
percent of the monthly actuarial rate because of the differential between the
amount of home health that is transferred into Part B in 1999 (two-sixths) and
the amount in Part B that is included in the premium calculation (two-sevenths).
PMID- 10185841
TI - Medicare program; Part A premium for 1999 for the uninsured aged and for certain
disabled individuals who have exhausted other entitlement--HCFA. Notice.
AB - This notice announces the hospital insurance premium for calendar year 1999 under
Medicare's hospital insurance program (Part A) for the uninsured aged and for
certain disabled individuals who have exhausted other entitlement. The monthly
Medicare Part A premium for the 12 months beginning January 1, 1999 for these
individuals is $309, the same as in 1998. The reduced premium for certain other
individuals as described in this notice is $170. Section 1818(d) of the Social
Security Act specifies the method to be used to determine these amounts.
PMID- 10185842
TI - Interim rules for group health plans and health insurance issuers under the
Newborns' and Mothers' Health Protection Act--IRS; DoL; HCFA. Interim rules with
request for comments.
AB - This document contains interim rules governing the Newborns' and Mothers' Health
Protection Act of 1996 (NMHPA). The interim rules provide guidance to employers,
group health plans, health insurance issuers, and participants and beneficiaries
relating to new requirements for hospital lengths of stay in connection with
childbirth. The rules contained in this document implement changes to the
Employee Retirement Income Security Act of 1974 (ERISA) and the Public Health
Service Act (PHS Act) made by NMHPA, and changes to the Internal Revenue Code of
1986 (Code) enacted as part of the Taxpayer Relief Act of 1997 (TRA '97).
Interested persons are invited to submit comments on the interim rules for
consideration by the Department of the Treasury, the Department of Labor, and the
Department of Health and Human Services (Departments) in developing final rules.
PMID- 10185843
TI - HIPAA Newborns' and Mothers' Health Protection Act--IRS. Notice of proposed
rulemaking by cross-reference to temporary regulations.
AB - Elsewhere in this issue of the Federal Register, the IRS is issuing temporary
regulations relating to minimum hospital length-of-stay requirements imposed on
group health plans with respect to mothers and newborns. The hospital length-of
stay requirements were added to the Internal Revenue Code by section 1531 of the
Taxpayer Relief Act of 1997. The IRS is issuing the temporary regulations at the
same time that the Pension and Welfare Benefits Administration of the U.S.
Department of Labor and the Health Care Financing Administration of the U.S.
Department of Health and Human Services are issuing substantially similar interim
final regulations relating to hospital length-of-stay requirements added by the
Newborns' and Mothers' Health Protection Act of 1996 to the Employee Retirement
Income Security Act of 1974 and the Public Health Service Act. The temporary
regulations provide guidance to employers and group health plans relating to the
new hospital length-of-stay requirements. The text of those temporary regulations
also serves as the text of these proposed regulations.
PMID- 10185844
TI - Medicare program; schedules of per-visit and per-beneficiary limitations on home
health agency costs for cost reporting periods beginning on or after October 1,
1998; correction--HCFA. Correction of notice with comment period.
AB - In the August 11, 1998 issue of the Federal Register (63 FR 42912), we published
a notice with comment period setting forth revised schedules of limitations on
home health agency costs that may be paid under the Medicare program for cost
reporting periods beginning on or after October 1, 1998. This document corrects
technical and typographical errors made in that document.
PMID- 10185845
TI - Health care programs: fraud and abuse; revised OIG exclusion authorities
resulting from Public Law 104-191; correction--Office of Inspector General (OIG).
HHS. Final rule; correcting amendment.
AB - This document contains corrections to the final regulations which were published
in the Federal Register of Wednesday, September 2, 1998 (63 FR 46676). The
regulations addressed revisions to the OIG's administrative sanction authorities
resulting from the Health Insurance Portability and Accountability Act of 1996,
along with technical and conforming changes to the OIG exclusion authorities. A
number of inadvertent errors appeared in the text of the regulations relating to
program integrity for the Medicare and State health care programs. As a result,
we are making corrections to two sections addressing the length of exclusion and
notice of intent to exclude in order to assure the technical correctness of these
regulations.
PMID- 10185846
TI - Medical devices; performance standards for dental and mammographic X-ray devices;
amendment--FDA. Proposed rule.
AB - The Food and Drug Administration (FDA) is proposing to exempt panoramic dental x
ray units from the requirement that they be manufactured with exposure timers
which automatically reset to zero upon premature termination of an exposure.
Removing the automatic timer reset requirement will not compromise the quality of
the radiographic image and will protect patients from being subjected to
unnecessary radiation due to repeat radiographs. FDA also proposes five changes
to align the performance standard with the equipment requirements issued under
the Mammography Quality Standards Act of 1992 (MQSA). First, the agency proposes
to remove any reference to the use of equipment not specifically designed for
mammography from the performance requirements for mammography equipment. Second,
FDA proposes that the mammographic field alignment requirements restrict the
irradiation beam to less than 2 percent of the source-image receptor distance
(SID) beyond the image receptor edges. Third, it is proposed that the definition
of an image receptor support device be amended to specify that it must provide a
primary protective barrier for any orientation of the x-ray tube and image
receptor support device assembly. Fourth, it is proposed that the useful beam
must be confined to the dimensions of the primary barrier provided by the image
receptor support device (except on the chest wall side). Fifth, it is proposed
that exposures not be permitted without the primary barrier in place.
PMID- 10185847
TI - Well grounded claims/duty to assist--VA. Advance notice of proposed rulemaking.
AB - The Department of Veterans Affairs (VA) is issuing an advance notice of proposed
rulemaking (ANPRM) to establish policy and guidance regarding what action, if
any, VA should take to develop evidence pertaining to benefit claims that are not
well grounded.
PMID- 10185848
TI - Health care fraud and abuse data collection program: reporting of final adverse
actions--Office of Inspector General (OIG), HHS. Notice of proposed rulemaking.
AB - This proposed rule would establish a new 45 CFR part 61 to implement the
statutory requirements of section 1128E of the Social Security Act, as added by
section 221(a) of the Health Insurance Portability and Accountability Act (HIPAA)
of 1996. Section 221(a) of HIPAA specifically directed the Secretary to establish
a national health care fraud and abuse data collection program for the reporting
and disclosing of certain final adverse actions taken against health care
providers, suppliers, or practitioners, and maintain a data base of final adverse
actions taken against health care providers, suppliers and practitioners.
PMID- 10185849
TI - Publication of the OIG's provider self-disclosure protocol--Office of Inspector
General (OIG), HHS. Notice.
AB - This Federal Register notice sets forth the OIG's recently-issued Provider Self
Disclosure Protocol. This Self-Disclosure Protocol offers health care providers
specific steps, including a detailed audit methodology, that may be undertaken if
they wish to work openly and cooperatively with the OIG to efficiently quantify a
particular problem and, ultimately, promote a higher level of ethical and lawful
conduct throughout the health care industry.
PMID- 10185851
TI - Medical: advance healthcare planning--VA. Proposed rule.
AB - This document proposes to amend the VA medical regulations to codify VA policy
regarding advance healthcare planning. The proposed rule sets forth a mechanism
for the use of written advance directives, i.e., a VA Living Will, a VA durable
power of attorney for health care, and a state-authorized advance directive. The
proposed rule also sets forth a mechanism for honoring verbal or nonverbal
instructions from a patient when the patient is admitted to care when critically
ill and loss of capacity may be imminent and the patient is not physically able
to sign an advance directive form, or the appropriate form is not readily
available. This is intended to help ensure that VA acts in compliance with
patients' wishes concerning future healthcare.
PMID- 10185850
TI - The development of technical and spectrum requirements for meeting federal, state
and local public safety agency communication requirements through the year 2010,
establishment of rules and requirements for priority access service--FCC. Final
rule.
AB - The Federal Communications Commission (Commission) adopted a First Report and
Order ("First Report") contemporaneously with a Third Notice of Proposed
Rulemaking that is summarized elsewhere in this edition of the Federal Register.
In the First Report, the Commission amends its rules relating to public safety
communications in the 764-806 MHz band ("700 MHz band") that the Commission
previously reallocated for public safety services and in general. This action
commences the process of assigning licenses for frequencies in the 700 MHz band
and addresses an urgent need for additional public safety radio spectrum and the
need for nationwide interoperability among local, state, and federal entities. By
this action, the Commission also takes additional steps toward achieving its
goals of developing a flexible regulatory framework to meet vital current and
future public safety communications needs and ensuring that sufficient spectrum
to accommodate efficient, effective telecommunications facilities and services
will be available to satisfy public safety communications needs into the 21st
century.
PMID- 10185852
TI - The development of technical and spectrum requirements for meeting federal, state
and local public safety agency communication requirements through the year 2010,
establishment of rules and requirements for priority access service--FCC.
Proposed rule.
AB - The federal Communications Commission (Commission) adopted a Third Notice of
Proposed Rule Making ("Third Notice") contemporaneously with a First Report and
Order ("First Report") that is summarized elsewhere in this edition of the
Federal Register. By its Third Notice, the Commission makes a range of proposals
and seeks comment relating to public safety communications in the 746-806 MHz
band ("700 MHz band") and in general. The Commission invites comment on how to
license the 8.8 megahertz of 700 MHz band spectrum designated as reserved in the
First Report and on whether to directly license each state or use a regional
planning process to administer the nationwide interoperability frequencies (2.6
MHz of spectrum designated in the First Report) pursuant to the national
interoperability plan to be established by the National Coordination Committee.
The Third Notice also discusses protection requirements for the Global Navigation
Satellite Systems and offers proposals to facilitate use of nationwide
interoperability in public safety bands below 512 MHz. Finally, because many of
the automated and intelligent machines and systems on which public safety
entities depend for their operations were not designed to take into account the
date change that will occur on January 1, 2000, the Commission also seeks comment
on how best to ascertain the extent, reach, and effectiveness of Year 2000
compliance initiatives that have been or are being undertaken by public safety
entities, to better understand the nature of the Year 2000 problem and the
potential risks posed to public safety communications networks. This action
addresses an urgent need for additional public safety radio spectrum and the need
for nationwide interoperability among local, state, and federal entities. By this
action, the Commission also takes additional steps toward achieving its goals of
developing a flexible regulatory framework to meet vital current and future
public safety communications needs and ensuring that sufficient spectrum to
accommodate efficient, effective telecommunications facilities and services will
be available to satisfy public safety communications needs into the 21st century.
PMID- 10185853
TI - Supplemental Security Income for the Aged, Blind and Disabled (SSI) program
demonstration project; treatment of cash received and conserved to pay for
medical or social services--SSA. Notice.
AB - The Commissioner of Social Security will conduct a demonstration project to test
how certain altered resources counting rules might apply in the SSI program. The
SSI program is authorized by title XVI of the Social Security Act (the Act). The
rules which will be tested are those that apply to the treatment of cash received
and conserved to pay for medical or social services. Cash which is received for
the purposes of payment for medical or social services is not counted as income
to the beneficiary when received. If cash received for medical or social services
which is not a reimbursement for these services already paid for by the
beneficiary is conserved, it is not counted as a resource for the calendar month
following the month of receipt, so long as it remains separately identifiable
from other resources of the individual. Beginning with the second calendar month
following the month of receipt, cash received for the payment of medical or
social services becomes a countable resource used in the determination of SSI
eligibility. The Health Care Financing Administration of the Department of Health
and Human Services (DHHS) is collaborating with the States of Arkansas, Florida,
New Jersey and New York and with the National Program Office at the University of
Maryland's Center on Aging, the Robert Wood Johnson Foundation, the Office of the
Assistant Secretary for Planning and Evaluation of the DHHS, the National Council
on Aging and Mathematica Policy Research (the evaluator) on a demonstration
project to provide greater autonomy to the consumers of personal assistance
services. Personal assistance services are help with the basic activities of
daily living, including bathing, dressing, transferring, toileting, and eating,
and/or instrumental activities of daily living such as housekeeping, meal
preparation, shopping, laundry, money management and medication management.
Consumers of personal assistance services who participate in this demonstration
will be empowered by purchasing the services they require (including medical and
social services) to perform the activities of daily living. In order to
accomplish the objective of the demonstration project, cash allowances and
information services will be provided directly to persons with disabilities to
enable them to choose and purchase services from providers which they feel would
best meet their needs. Medicaid is the predominant source of public financing for
personal assistance services programs for the aged, blind and disabled. The
demonstration which will permit the States of Arkansas, Florida, New Jersey and
New York to waive certain requirements under title XIX of the Act to participate
in this "Cash and Counseling" demonstration is within the authority granted to
the Secretary of Health and Human Services (HHS) by section 1115 of the Act.
Medicaid beneficiaries who participate in this demonstration will be given cash
to purchase the services they need from traditional and nontraditional providers
as they deem appropriate. Counseling will be available for these beneficiaries to
assist them in effective use of funds allotted for personal assistance services.
Many of the Medicaid beneficiaries who participate in the Cash and Counseling
demonstration will be SSI beneficiaries or belong to coverage groups using
eligibility methodologies related to those of the SSI program under title XIX of
the Act. The Commissioner of Social Security wishes to test the appropriateness
of current SSI rules which require counting cash received for the purchase of
medical or social services as resources if retained for more than one month after
the month of receipt. The test will also be used to assist the Secretary of HHS
in testing the possibility of providing greater autonomy to the consumers of
personal assistance services by empowering them to purchase the services they
require (including medical and social services) to perform their activities of
daily living. (ABSTRACT TRUNCATED)
PMID- 10185854
TI - Medicare program; revisions to payment policies and adjustments to the relative
value units under the physician fee schedule for calendar year 1999--HCFA. Final
rule with comment period.
AB - This final rule makes several policy changes affecting Medicare Part B payment.
The changes that relate to physicians' services include: resource-based practice
expense relative value units (RVUs), medical direction rules for anesthesia
services, and payment for abnormal Pap smears. Also, we are rebasing the Medicare
Economic Index from a 1989 base year to a 1996 base year. Under the law, we are
required to develop a resource-based system for determining practice expense
RVUs. The Balanced Budget Act of 1997 (BBA) delayed, for 1 year, implementation
of the resource-based practice expense RVUs until January 1, 1999. Also, BBA
revised our payment policy for nonphysician practitioners, for outpatient
rehabilitation services, and for drugs and biologicals not paid on a cost or
prospective payment basis. In addition, BBA permits certain physicians and
practitioners to opt out of Medicare and furnish covered services to Medicare
beneficiaries through private contracts and permits payment for professional
consultations via interactive telecommunication systems. Furthermore, we are
finalizing the 1998 interim RVUs and are issuing interim RVUs for new and revised
codes for 1999. This final rule also announces the calendar year 1999 Medicare
physician fee schedule conversion factor under the Medicare Supplementary Medical
Insurance (Part B) program as required by section 1848(d) of the Social Security
Act. The 1999 Medicare physician fee schedule conversion factor is $34.7315.
PMID- 10185855
TI - Medicare program; sustainable growth rate for fiscal year 1999--HCFA. Notice with
comment period.
AB - This notice announces the fiscal year 1999 sustainable growth rate (SGR) for
expenditures for physicians' services under the Medicare Supplementary Medical
Insurance (Part B) program as required by section 1848(f) of the Social Security
Act. The SGR for fiscal year 1999 is -0.3 percent. The negative fiscal year 1999
SGR is driven by the projected drop in Medicare fee-for-service enrollment.
PMID- 10185856
TI - The toughest sell in town.
PMID- 10185857
TI - All in the so-called family.
PMID- 10185858
TI - HMOs--the good guys again?
PMID- 10185859
TI - Naming names: two surveys' 'best'.
PMID- 10185860
TI - Compensation monitor. All health care is local, but its financing is universal.
PMID- 10185861
TI - A plan physicians find appealing: redefining employer contributions.
PMID- 10185862
TI - Care management: the next wave of managed care? A conversation with Peter I.
Juhn, M.D.. Interview by Patrick Mullen.
PMID- 10185864
TI - 'I'd never even thought about joining a union'.
PMID- 10185863
TI - Advances in HIV/AIDS care require hard choices.
PMID- 10185865
TI - Private lives: how much should doctors account for behavior outside of medicine?
PMID- 10185866
TI - Stark II wants contribution plan installed before payment period begins.
PMID- 10185867
TI - Managed care outlook. Enrollment still rising--and now, HMO count is, too.
PMID- 10185868
TI - Academic institutions--overpaying their administrators?
PMID- 10185869
TI - Thou shalt follow guidelines (please!).
PMID- 10185870
TI - Just what the devil is population-based care?
PMID- 10185871
TI - A conversation with Nancy W. Dickey, M.D.. Interview by Patrick Mullen.
PMID- 10185872
TI - We have the tools for safer prescribing and dispensing.
PMID- 10185874
TI - Hospital-owned health plans grow.
PMID- 10185873
TI - Limiting access to managed care: is 'no job, no health benefits' fair?
PMID- 10185875
TI - Consumer health information services: a growing area in hospital libraries.
PMID- 10185876
TI - Information technology committee. Basic principles for a simple intranet.
PMID- 10185877
TI - InfoBeat ... consumer health information.
PMID- 10185878
TI - Accessing the Internet: tips for hospital librarians.
PMID- 10185879
TI - Patient education Web sites.
PMID- 10185880
TI - Cheaper by the dozen: low cost consumer health resources.
PMID- 10185881
TI - More motivation for automation.
PMID- 10185882
TI - Disease management on the Web.
PMID- 10185883
TI - Facing the challenge of the '90s. Interview by Tyler L. Chin.
PMID- 10185884
TI - Building a robust network for a bargain price.
PMID- 10185885
TI - Can chief security officers protect data from prying eyes?
AB - New rules, new laws and new technologies are a few of the reasons why more health
care organizations are likely to hire chief security officers. Now more than
ever, many experts contend, health care organizations need one person dedicated
to the job of protecting health care information as it is created, stored,
manipulated and transmitted by hundreds of people every day.
PMID- 10185886
TI - Network computing.
AB - Pioneering health care organizations are saving money and gaining greater control
of their networks by trading their PCs in for thin clients. But the devices are
far from pervasive in health care.
PMID- 10185887
TI - Windows NT continues its battle for market share.
AB - A growing number of health care organizations are implementing applications that
run on the Microsoft Windows NT network operating system. But most of the early
adopters are applying NT at the department level rather than using it for
enterprisewide tasks. And the many flavors of Unix continue to dominate the
market for network operating systems in health care.
PMID- 10185888
TI - Sending out an SOS: the role of help desks.
AB - Help desks are a relatively new phenomenon among health care organizations. Just
a few years ago, centralized technical support for computer users was viewed as
an expensive and unnecessary luxury. But with the onslaught of larger and more
complex organizations, including integrated delivery systems, the need for
structured technical support has grown.
PMID- 10185889
TI - Seasick? Help is on the way. A new telemedicine system uses a satellite to link a
cruise ship's physicians with specialists in California.
PMID- 10185890
TI - Web site survey comments.
PMID- 10185891
TI - Internet/intranets. An easier way to make rules.
PMID- 10185892
TI - Leading the way. Interview by Jennifer A. Gilbert.
PMID- 10185893
TI - Keeping caregivers off hold.
PMID- 10185894
TI - Gathering clinical data. A clinical data repository provides the foundation for
computer-based patient records.
PMID- 10185895
TI - Improving the odds.
AB - Health care providers are using information systems to gather and analyze data
that will help make entering capitated managed care contracts less of a gamble.
PMID- 10185896
TI - Outsourcing. The cure for I.T. headaches?
PMID- 10185897
TI - Facing new regulations, home care agencies turn to automation.
PMID- 10185898
TI - The challenging home care market.
PMID- 10185899
TI - Teaching effective security.
PMID- 10185900
TI - Checking up on physicians.
PMID- 10185901
TI - Improving continuing care for medically fragile children: collaboration between
home care and hospital social work.
PMID- 10185902
TI - The Families and Health Care Project--moving family caregivers to the forefront.
PMID- 10185904
TI - Top 10 trends for the future of emergency departments.
PMID- 10185903
TI - Identifying the special needs of male caregivers.
PMID- 10185905
TI - Managed care impacts emergency services, staffing, and reimbursement.
PMID- 10185906
TI - Emergency departments are symbols of access to care.
PMID- 10185907
TI - PSOs are windows of opportunity to capture the premium and restore patient
provider relationships.
PMID- 10185908
TI - PSOs are opportunity to create a new kind of managed care.
PMID- 10185909
TI - What will it take to become a PSO?
PMID- 10185910
TI - Compliance with COBRA/EMTALA screening criteria.
PMID- 10185912
TI - Milwaukee EDs join forces on Internet.
PMID- 10185911
TI - Cater to children in your ED.
PMID- 10185913
TI - New EMTALA guidelines hot off the press: here's what your ED needs to know.
PMID- 10185914
TI - Breaking the chain: how new Medicare changes threaten continuum of care.
AB - Recent actions by the Health Care Financing Administration (HCFA) and the Office
of the Inspector General could drive up inpatient lengths of stay, discourage
hospital ownership of home health agencies, and make seamless transitions across
the continuum of care more difficult than ever, some experts say. As of Oct. 1,
HCFA's new transfer payment policy has already taken effect, penalizing hospitals
for discharging patients with certain conditions directly to postacute care.
Critics contend that the new policy will encourage hospitals to keep these
patients in acute care longer and cost the hospital industry approximately $600
million per year. The transfer payment rules also raise thorny issues for
discharge planners, who need to make absolutely sure they know what sort of care
patients receive once they leave the hospital, experts say.
PMID- 10185915
TI - Report questions ethics of home health referrals.
AB - Elkhart (IN) General Hospital has made its home health agency an integral partner
in the success of its open heart surgery program, using home health as a vehicle
to help prevent infections and resulting hospital readmissions. The open heart
surgery pathway tracks patients from surgery to recovery, post-op care to home
health, and then to outpatient cardiac rehabilitation. It was developed in
cooperation with the hospital's home health agency and makes provisions for four
home care visits. While non-affiliated home health agencies can't be compelled to
use the hospital's pathway, case managers at Elkhart have shared the path with
representatives from these agencies and explained to them that it represents the
hospital's standard of care.
PMID- 10185916
TI - CMs coordinate with home care on continuum path.
PMID- 10185917
TI - Reviewing the data: what ORYX means to you.
AB - The role of case managers in reviewing and analyzing outcomes data as part of the
Joint Commission on Accreditation of Healthcare Organizations' ORYX initiative is
often neglected. Case managers who become involved in reviewing ORYX data should
first find out who the data vendor is and what methods are used for severity
adjustment or risk adjustment. Information from ORYX can be used to evaluate
areas of potential improvement in the case management program and identify ways
to refine and add to existing clinical pathways.
PMID- 10185919
TI - Avoid mistakes when buying CM (case management) software.
PMID- 10185918
TI - Asthma disease management program cuts readmissions.
PMID- 10185920
TI - HIPAA requirements may dwarf Y2K problems.
PMID- 10185921
TI - Survive by keeping up with information technology.
PMID- 10185922
TI - Medicare patients stay in hospital too long.
PMID- 10185923
TI - 1998 salary survey results. Clinical competencies are key to job market success.
PMID- 10185924
TI - When the well runs dry: making the switch to disease management.
AB - If you've shortened lengths of stay and cut costs as much as possible short of
jeopardizing patient care, it may be time to take what some experts consider the
next step beyond traditional case management: hospital-based disease management.
Disease management involves not merely making a few process improvements but
actually changing the underlying structure of how care is provided, particularly
for patients with chronic conditions. Although clinical pathways can help in
making the transition to a disease management approach, the most important factor
to consider is how to get everyone--both within your facility and along the
continuum--on the same page when it comes to managing chronically ill patients.
PMID- 10185925
TI - DM programs must be unique to each facility.
PMID- 10185926
TI - Outpatient diabetes center cuts inpatient costs.
AB - By shifting its education of patients newly diagnosed with Type I diabetes from
the acute care setting to an outpatient clinic, Children's Hospital of Wisconsin
in Milwaukee has cut its costs per case from as much as $4,500 to $900, while
inpatient length of stay has dropped from three days to one, even for
metabolically unstable patients. Despite the cost decreases, however,
reimbursement remains a problem. Patients and their family members receive 12 to
15 hours of education during three half-day sessions in the clinic, but insurance
companies often shy away from paying for outpatient education programs. Despite
the reluctant support of insurance companies, the case manager in charge of the
diabetes program has taken steps to align charges with the actual cost of
staffing and running the diabetes center, factoring in a 30% profit margin.
PMID- 10185928
TI - Jefferson CHF pathway includes severity adjustment.
PMID- 10185927
TI - AHA blasts federal policy on home health ownership.
AB - A month after the Health Care Financing Administration implemented its new
transfer payment policy, the American Hospital Association has blasted federal
investigators for unfairly targeting hospital discharge planners. According to
the association, recent actions by investigators suggest that the government is
set to crack down on hospitals that own home health agencies, and particularly on
discharge planners, who remain under suspicion for allegedly limiting patient
choice in steering patients to hospital-owned agencies. The AHA's senior
associate director of policy development stresses the importance of reviewing and
correcting all discharge policies to make sure financial incentives aren't
driving discharge decisions.
PMID- 10185929
TI - Developing an information management plan.
AB - With demands for outcomes measurement data increasing, case managers can quickly
become overburdened with data-collection responsibilities. That's why it's more
important than ever to coordinate information flow and minimize redundant data
gathering by case managers. The first step in developing an information
management plan is to identify who in the organization is gathering, analyzing,
and using performance data. That means being aware of what departments outside of
case management are doing. Then the case management department can design
electronic linkages with computerized databases that contain information
necessary to support improvement efforts. Any information management plan should
contain provisions governing the release of performance measurement data. Issues
to consider include: the patient's right to confidentiality; JCAHO standards and
state statutes pertaining to hospital information systems; hospital policies and
procedures on departmental information systems; and physicians' and employees'
right to confidentiality.
PMID- 10185930
TI - Medical society-health plan collaboration takes off in Virginia.
PMID- 10185931
TI - AHERF's collapse: a signal moment for hospital systems?
PMID- 10185932
TI - Rethinking the market: two physician organization experts offer chaos-tested
advice. Interview by Mark Hagland.
PMID- 10185933
TI - Challenge to HCFA survey and enforcement procedures could end up before Supreme
Court.
PMID- 10185934
TI - HCFA exempts swing beds from transfer rule; provider group worries about unfair
advantage.
PMID- 10185935
TI - Medicare rehab patients flow through the continuum in highly varied manner.
PMID- 10185936
TI - Quarterly financial results of post acute/subacute companies.
PMID- 10185937
TI - HCFA gives progress report on oversight, enforcement of nursing facilities; 100
homes targeted.
PMID- 10185938
TI - Industry keeps up effort to head off user fees.
PMID- 10185939
TI - Investment report sees PPS as a positive for SNFs in the long run.
PMID- 10185941
TI - Short-stay MDS almost ready for field testing; instrument better suited for
subacute care patients.
PMID- 10185940
TI - Health plans react to changing Medicare managed care market; long-term outlook
still positive.
PMID- 10185942
TI - Rewriting the contract with your suppliers.
PMID- 10185943
TI - Fine-tuning foodservice.
PMID- 10185944
TI - Why subacute still makes financial sense.
PMID- 10185945
TI - Who makes what. Contemporary Long Term Care's 1998 nursing staff survey.
PMID- 10185946
TI - Final acts.
PMID- 10185947
TI - Going pro. Caregivers and managers set higher professional standards.
PMID- 10185948
TI - Don't cut corners when hiring frontline employees.
PMID- 10185949
TI - The pursuit of happiness. Antidepressants are still underused in long-term care.
PMID- 10185950
TI - Five minutes with Steve McConnell. Interview by Elise Nakhnikian.
PMID- 10185951
TI - Rehabilitation under PPS.
PMID- 10185952
TI - Competing with nursing homes for market share.
PMID- 10185953
TI - Profiles. 20 who made a difference.
PMID- 10185954
TI - Milestones. 20 key events that shaped long-term care.
PMID- 10185955
TI - Progress report. A pioneer in the field of gerontology takes stock of long-term
care.
PMID- 10185956
TI - Acquisition binge continues. Assisted living is especially hot--but for how long?
PMID- 10185957
TI - Fair Labor Standards Act: are you paying by the rules?
PMID- 10185958
TI - OSHA on the Internet.
PMID- 10185959
TI - The dangers of overdocumentation.
PMID- 10185960
TI - Thinking outside the box essential with risk contracting ventures.
PMID- 10185961
TI - NJ hospital turns structure upside-down.
PMID- 10185962
TI - Pennsylvania PHO chooses mission and cuts costs.
PMID- 10185963
TI - Learn a little risk management.
PMID- 10185964
TI - New tools ask patients to report, not rate.
PMID- 10185965
TI - Learn to manage frail elderly patients for Medicare risk contracting success.
PMID- 10185966
TI - Finding frail elderly key to managing them.
PMID- 10185967
TI - Manage Medicaid populations under risk contracts.
AB - This is the first of a series on how PHOs, IPAs, and other provider groups can
manage a population of patients, particularly when involved in risk contracting.
The first stories focus on the Medicaid population. Look in September's issue for
stories about how to establish disease management guidelines for a general
population.
PMID- 10185968
TI - Help Medicaid patients be smarter consumers.
PMID- 10185969
TI - Arizona paves way for Medicaid risk contracts.
PMID- 10185970
TI - Five hearts or thumbs up: health plans rank MDs.
PMID- 10185971
TI - Avoid common pitfalls of hospital system mergers.
PMID- 10185972
TI - Risk contracting calls for more use of disease management.
AB - This is the second of a series on how PHOs, IPAs, and other provider groups can
manage a population of patients. The August issue of PHO Advisor included stories
on managing Medicaid populations under risk contracts and establishing wellness
programs.
PMID- 10185973
TI - Look for ways to reduce liability exposure.
PMID- 10185974
TI - Hospital mergers continue as managed care pressures mount nationwide.
PMID- 10185975
TI - Influence of a critical path management tool in the treatment of acute myocardial
infarction. Clinical Quality Improvement Network Investigators.
AB - OBJECTIVE: The primary objective of this study was to determine the effect of
implementing a critical path on use of proven efficacious therapies and outcomes
in patients admitted to a hospital with acute myocardial infarction (AMI). The
secondary objectives were to evaluate the use of unproven medications and to
develop an understanding of the factors associated with adverse in-hospital
outcomes in these patients. STUDY DESIGN: A nonrandomized before-after study
design was used to evaluate the efficacy of a critical path instrument in
patients admitted to hospital with AMI. PATIENTS AND METHODS: Consecutive
patients admitted with AMI in nine participating hospitals were enrolled in the
study. The critical path instrument consisted of a locally developed, preprinted
physician order form. Practice patterns were determined before (n = 2305) and
after (n = 2349) implementation of the critical path by primary chart review.
Multivariate analysis of risk factors for mortality was performed on a combined
database of 6088 AMI patients. RESULTS: The use of acetylsalicylic acid (ASA),
nitrates, and beta blockers increased significantly by 3%, 2%, and 9%,
respectively, after implementation of the critical path. Use of thrombolytics
remained stable at 41%, and calcium channel blocker use decreased significantly
by 8%. In-hospital mortality decreased by 1%. There was less use of ASA,
nitrates, beta blockers, and thrombolytic therapy in women and the elderly.
Multivariate analysis showed that advanced age was associated with increased
mortality risk, whereas ASA, beta blockers, nitrates, and calcium channel
blockers were associated with reduced mortality risk. CONCLUSION: Implementation
of a critical path resulted in increased use of proven efficacious therapies,
reduced use of noneffective therapy, and a trend toward reduced mortality.
PMID- 10185976
TI - Infectious diseases and anemia in a sample of out-of-treatment drug users.
AB - OBJECTIVE: To understand how the prevalence of anemia, human immunodeficiency
virus (HIV), and syphilis in a sample of out-of-treatment drug users affected
delivery of care in a managed care model. STUDY DESIGN: A snowball sampling
design with multiple zero order contacts was used in targeted census tracts with
a high incidence of illicit drug use and sexually transmitted diseases. PATIENTS
AND METHODS: Out-of-treatment drug users were recruited as part of a national
multisite study of HIV risk behaviors in this population. Subjects were recruited
using targeted community-based sampling. RESULTS: The rate of individuals who
tested positive for both syphilis and HIV was 2.5 times greater than those who
tested positive for syphilis only and 2.8 times greater than those who tested
positive for HIV only. Of the men, 16.1% were anemic, and 33.3% of women were
anemic. Rates of HIV (10.7%) and syphilis (19.8%) were found to be high among
both male and female drug users. These statistics, coupled with the prevalence of
anemia, indicate that drug users have many more problems other than drug use, a
conclusion which can have an impact on how managed care plans approach drug
users. CONCLUSION: A multipronged interdisciplinary approach may be warranted for
both the patient and the managed care organization.
PMID- 10185977
TI - Assessing the economic value of antihypertensive medications.
AB - OBJECTIVE: To assess the economic value of antihypertensive medications by
comparing the likelihood of coronary heart disease and stroke events and
subsequent event treatment costs. STUDY DESIGN: Duration of blood pressure
reduction was used to profile event risk reduction of three antihypertensive
medications. METHODS: We used clinical data to determine the duration of blood
pressure reduction achieved with use of two angiotensin converting enzyme
inhibitors and one angiotensin II receptor antagonist. We then used trough-to
peak ratios to calculate the reduction in risk of coronary heart disease and
stroke events associated with each medication. RESULTS: Across a number of
different event treatment cost and population size estimates, the economic value
of different medications can be assessed. CONCLUSION: Our method for assessing
the economic value of antihypertensive medications can be applied to other drug
classes and can be further refined by integrating patient population and other
risk-related data.
PMID- 10185978
TI - The rationale for skin cancer screening and prevention.
AB - Skin cancer, the most common malignancy in the United States, accounts for
considerable morbidity and mortality. Efforts at lessening the burden of this
disease are possible through both primary and secondary prevention, although some
barriers may detract from the ability of primary care physicians to perform skin
cancer screening. Public education combined with increased vigilance by
physicians and other health professionals may significantly alter the morbidity
and mortality associated with this disease entity.
PMID- 10185979
TI - Effects of an asthma management program on the asthmatic member: patient-centered
results of a 2-year study in a managed care organization.
AB - OBJECTIVE: To report the results of a 2-year pilot program of asthma education
based on National Heart, Lung, and Blood Institute treatment guidelines. PATIENTS
AND METHODS: Asthmatic members (n = 6698) of a managed care organization received
education about their condition directly or through their primary care physician.
Medical and pharmacy administrative claims data were reviewed to measure acute
asthma events and prescribed therapies in the first (the baseline) and second
years of the study. The claims data were augmented by member surveys from a
stratified random sample of 2734 asthmatic patients who were members (6 years of
age or older) in the baseline year. RESULTS: Compared with the first year,
asthmatic members received fewer inpatient services and the proportion of
asthmatic members prescribed oral inhaled corticosteroids increased 30% in the
second year. Health-related quality of life, measured with validated general and
disease-specific instruments; satisfaction with the quality of care; exposure to
patient education; knowledge of the disease; and member's confidence in their
ability to manage their disease showed statistically significant improvements
during the follow-up year of the program for both adult and child asthmatic
members. CONCLUSION: For asthmatic members of this health plan, a comprehensive
asthma health management program improved processes of care and outcomes.
PMID- 10185981
TI - Managed care clinical corner: a case for large-core biopsy procedures in the
diagnosis of breast cancer.
PMID- 10185980
TI - Evaluating and improving the delivery of heart care: the University of Michigan
experience.
AB - With increasing pressure to curb escalating costs in medical care, there is
particular emphasis on the delivery of cardiovascular services, which account for
a substantial portion of the current healthcare dollar spent in the United
States. A variety of tools were used to improve performance at the University of
Michigan Health System, one of the oldest university-affiliated hospitals in the
United States. The tools included initiatives to understand outcomes after
coronary bypass operations and coronary angioplasty through use of proper risk
adjusted models. Critical pathways and guidelines were implemented to streamline
care and improve quality in interventional cardiology, management of myocardial
infarction, and preoperative assessment of patients undergoing vascular
operations. Strategies to curb unnecessary costs included competitive bidding of
vendors for expensive cardiac commodities, pharmacy cost reductions, and changes
in nursing staff. Methods were instituted to improve guest services and
partnerships with the community in disease prevention and health promotion.
PMID- 10185982
TI - Mental disorders in the primary care sector: a potential role for managed care.
AB - This activity is designed for leaders and managers of managed care organizations
and for primary care physicians involved in evaluating, treating, and caring for
patients with mental disorders. GOAL: To provide a better understanding of
primary care patients' needs for mental health services and how managed care
companies might best address these needs. OBJECTIVES: 1. Describe problems in
detection of mental disorders 2. Discuss the specific ways in which treatments
can be improved for mental disorders under managed care systems.
PMID- 10185983
TI - Determining whether managed care formularies meet the needs of pediatric
patients.
AB - This activity is designed for healthcare providers making formulary decisions for
managed care organizations. GOAL: To help clinicians determine whether managed
care formularies meet the needs of pediatric patients. OBJECTIVES: 1. List
general considerations for establishing a pediatric drug formulary. 2. Understand
the importance of growth and development when selecting drug therapy for
pediatric patients. 3. Discuss potential difficulties with administering
medications during school hours. 4. Identify specific medications within the drug
classes of antibiotics, asthma medications, endocrine, and gastrointestinal
agents that should be available on a pediatric drug formulary.
PMID- 10185984
TI - Demographics and cost of epilepsy. Based on a presentation by John F. Annegers,
PhD.
AB - Over the past decade, there has been considerable interest in cost-of-illness
studies for many diseases, including epilepsy. However, the nature of epilepsy
and the wide spectrum of its clinical course make it difficult to assess the
overall costs of the disease. Differences in incidence rates by age, gender,
etiology, and other demographic variables further complicate the task of
assessing costs. The incidence is highest in the first decade of life and in the
elderly. A cost-simulation study based on incidence and prognosis sheds light on
how costs are estimated. This type of study also serves as a prelude to cost-of
disease studies, cost-benefit studies, and cost-effectiveness studies.
Approximately 70% of patients with new-onset epilepsy will achieve remission
relatively quickly and at relatively low cost. The picture is far less rosy for
patients with intractable seizures; for them, the outcome is fair to poor, and
the lifetime costs are high. An empiric version of the cost-stimulation study is
now under way. Its objectives are to identify incidence cases of epilepsy in two
cohorts, collect longitudinal data on each case, estimate the costs of care over
time and across service, measure patterns of resource use over time, and use the
resultant direct cost estimates as a national cost model.
PMID- 10185985
TI - Anticonvulsants: choices and costs. Based on a presentation by Nina Graves,
PharmD, FCCP.
AB - Epilepsy is not a single disease but a constellation of different syndromes and
different seizure types. Consequently, establishing a diagnosis on which to base
therapy can be complicated. The most commonly used antiepileptic drugs (AEDs)
fall into two broad categories: the older AEDs introduced between 1912 and 1973
and the newer AEDs introduced since 1993. The older AEDs have many off-label
uses, whereas the newer AEDs, with the exception of gabapentin and lamotrigine,
are used exclusively for the treatment of epilepsy. All AEDs are associated to
varying degrees with adverse effects on the central nervous system,
gastrointestinal tract, blood, liver, and skin. The older AEDs are less expensive
than the newer AEDs, but because the newer agents are available in both titration
and maintenance-dose strengths, cost savings are possible. Use of the high
strength dose of a newer AED represents a huge cost saving per day compared with
using the low-strength dose. Further savings can be realized in the managed care
arena if pharmacists are involved in getting patients onto high-strength tablets
as quickly as possible.
PMID- 10185986
TI - Referral centers and specialized care. Based on a presentation by Ronald P.
Lesser, MD.
AB - Appropriate diagnosis and treatment and the correct use of specialized services
at epilepsy referral centers make it possible to control seizures relatively
quickly in a large number of patients. Timeliness is extremely important,
however, because delaying treatment decreases the likelihood of achieving
complete remission from seizures. Epilepsy has a tremendous impact on quality of
life. Concerns about concomitant illnesses, seizure-related injuries, and the
psychosocial effects of seizures and anticonvulsants on patients are very real
and should be addressed. An accurate diagnosis is the first step in effective
seizure control, because not every patient with a seizure disorder has epilepsy.
The second step is choosing an antiepileptic drug (AED) that is appropriate for
the patient and using the correct dose and dosing schedule. When seizures remain
uncontrolled or are poorly controlled despite medical therapy, the patient should
be reevaluated to ascertain why the drug or drug combination is not working. The
reason may be the wrong diagnosis, the wrong drug, or the wrong dose. If the
seizures remain uncontrolled, the patient should be evaluated as a possible
candidate for epilepsy surgery. If the patient is a good candidate, a presurgical
work-up that includes monitoring and imaging studies should be performed, ideally
at an epilepsy referral center. Quality care depends on access, communication,
and knowledge, which involves patients who know how to achieve the best possible
seizure control, doctors who are well informed and know what to do to ensure that
their patients are receiving the best care, and mechanisms that permit
consultation among everyone involved in caring for patients with epilepsy.
Developing a system of quality, cost-effective care for the management of
epilepsy also offers an excellent opportunity to apply such a system to the
larger arena of medical care in general.
PMID- 10185987
TI - Determining costs and cost-effectiveness of epilepsy.
PMID- 10185988
TI - Technology assessment, coverage decisions, and conflict: the role of guidelines.
AB - As pressure grows for health plans to be accountable for increasing quality of
care within a cost-control environment, coverage of new technologies becomes a
particularly challenging issue. For a number of reasons, health plans have
adopted evidence-based methods for guiding technology decisions. The
implementation of these methods has not been free of controversy, and conflicts
have arisen between plans and proponents of technologies who often use the
political and legal arena in an attempt to secure coverage. Unless these
conflicts are resolved, the healthcare system may have difficulty meeting cost
and quality objectives. Technology assessment and coverage process guidelines and
flexible coverage approaches may be possible ways of resolving these conflicts.
PMID- 10185989
TI - Technology assessment of medical devices at the Center for Devices and
Radiological Health.
AB - We reviewed the Food and Drug Administration's regulatory process for medical
devices and described the issues that arise in assessing device safety and
effectiveness during the postmarket period. The Center for Devices and
Radiological Health (CDRH), an organization within the Food and Drug
Administration, has the legal authority and responsibility for ensuring that
medical devices marketed in the United States are both reasonably safe and
effective for their intended use. This is an enormous challenge given the
diversity of medical devices and the large number of different types of devices
on the market. Many scientific and regulatory activities are necessary to ensure
device safety and effectiveness, including technology assessment, albeit in a
manner quite different from that of conventional technology assessment. The basic
approach taken at the CDRH to ensure device safety and effectiveness is to
develop an understanding of the way in which a medical device works and how it
will perform in clinical situations.
PMID- 10185990
TI - Role of technology assessment in health benefits coverage for medical devices.
AB - With the profusion of new medical technology, managed care organizations are
faced with the challenge of determining which medical devices and services
warrant health benefits coverage. To aid in this decision-making process, managed
care companies turn to technology assessment, a process that differs from the
Food and Drug Administration's review of medical devices. Health plans typically
use a structured approach to implementing coverage requirements in employer group
benefits contracts and use technology assessment to evaluate the scientific
evidence of effectiveness to support coverage decisions. Also important is the
societal context for decisions regarding coverage for new technologies and the
options being considered by policy makers for accountability in technology
assessment by private insurers and health plans.
PMID- 10185991
TI - Transmyocardial laser revascularization: a qualitative systematic review.
AB - OBJECTIVE: To evaluate the status of transmyocardial laser revascularization
(TMLR) from an evidence-based perspective to help hospitals make resource
management decisions. STUDY DESIGN: Qualitative systematic review of the clinical
literature. METHODS: We searched the reference databases MEDLINE, BIOSIS, EMBASE,
SciSearch, and Current Contents to identify all articles related to TMLR
published between January 1985 and March 1997. We collected, analyzed, and
summarized clinical studies in evidence tables. RESULTS: The cumulative evidence
available in the medical literature regarding the safety and effectiveness of
TMLR encompasses approximately 2000 patients treated worldwide, primarily those
with medically refractory angina. Preliminary data suggest that TMLR has an
acceptable survival rate and effectively relieves angina in approximately 75% of
patients. Data showing improved myocardial perfusion, cardiac function, or
prognosis are inconclusive. The mechanism by which TMLR relieves angina is not
yet known. CONCLUSIONS: Early evidence regarding TMLR suggests it will be useful
for treating patients with end-stage coronary artery disease. Definitive
recommendations await critical analysis of the results of ongoing randomized
clinical trials, post-market surveillance studies, and third-party payer
acceptance.
PMID- 10185992
TI - Use of an intravenous contrast agent (Optison) to enhance echocardiography:
efficacy and cost implications. Optison Multicenter Study Group.
AB - OBJECTIVE: To compare the overall diagnostic costs associated with non-contrast
and contrast echocardiography. STUDY DESIGN: Phase III clinical trial. PATIENTS
AND METHODS: In a secondary analysis of data from a phase III clinical trial of
the intravenous contrast agent Optison, we compared the costs associated with
obtaining a diagnosis in 203 patients who underwent non-contrast and contrast
echocardiography. Costs for the initial test and any follow-up tests were derived
from adjusted Medicare charges and a transition-1 microcost accounting system.
RESULTS: Diagnostic yield from echocardiograms was 87% with the use of Optison (3
mL) and 49% when no contrast agent was used (P < 0.001). Because technically
inadequate echocardiograms were more common in the non-contrast group, follow-up
testing was recommended for 42% of patients in this group compared with 12% of
those who had undergone a contrast-enhanced echocardiogram (P < 0.001). Although
use of Optison increased the initial diagnostic cost by $125, overall costs were
17% lower when Optison was used (P < 0.0001). Use of Optison also resulted in a
17% to 70% decrease in confirmatory transesophageal echocardiography,
catheterization, and nuclear studies. Optison improved diagnostic accuracy by 2.7
fold in patients with an initial non-diagnostic echocardiogram, resulting in a
substantial cost savings of $269 per patient.
PMID- 10185993
TI - Device evaluation and coverage policy in workers' compensation: examples from
Washington State.
AB - Workers' compensation health benefits are broader than general health benefits
and include payment for medical and rehabilitation costs, associated indemnity
(lost time) costs, and vocational rehabilitation (return-to-work) costs. In
addition, cost liability is for the life of the claim (injury), rather than for
each plan year. We examined device evaluation and coverage policy in workers'
compensation over a 10-year period in Washington State. Most requests for device
coverage in workers' compensation relate to the diagnosis, prognosis, or
treatment of chronic musculoskeletal conditions. A number of specific problems
have been recognized in making device coverage decisions within workers'
compensation: (1) invasive devices with a high adverse event profile and history
of poor outcomes could significantly increase both indemnity and medical costs;
(2) many noninvasive devices, while having a low adverse event profile, have not
proved effective for managing chronic musculoskeletal conditions relevant to
injured workers; (3) some devices are marketed and billed as surrogate diagnostic
tests for generally accepted, and more clearly proven, standard tests; (4)
quality oversight of technology use among physicians may be inadequate; and (5)
insurers' access to efficacy data adequate to make timely and appropriate
coverage decisions in workers' compensation is often lacking. Emerging technology
may substantially increase the costs of workers' compensation without significant
evidence of health benefit for injured workers. To prevent ever-rising costs, we
need to increase provider education and patient education and consent, involve
the state medical society in coverage policy, and collect relevant outcomes data
from healthcare providers.
PMID- 10185994
TI - The limited state of technology assessment for medical devices: facing the
issues.
AB - Medical devices are an integral part of clinical practice and account for a
substantial proportion of the national health budget. Clinical testing and
regulation of medical devices, however, is vastly different from and inferior to
the testing and regulation of drugs. As managed care organizations begin to exert
controls on device use, providers are being caught between the policies of their
organizations and the demands of device manufacturers and patients, who want
wider access to devices. We outline several reasons for the poor state of medical
device evaluations and the dangers of using devices without adequate information,
and include the recently developed device assessment and reporting guidelines
created by the Task Force on Technology Assessment of Medical Devices.
PMID- 10185995
TI - Healthcare technology assessment: methods, framework, and role in policy making.
AB - This activity is designed for healthcare organization managers and clinicians,
particularly those involved in technology-related decisions, including coverage
decisions, technology acquisition, practice guideline development, and evidence
based medicine. GOAL: To provide a basic understanding of the principles,
methods, and systematic framework of healthcare technology assessment.
OBJECTIVES: 1. Understand the role of healthcare technology assessment in policy
making and the technical properties and impact assessed. 2. Become familiar with
the categories and basic attributes of methods used in healthcare technology
assessment. 3. Comprehend the ten-step framework for conducting a healthcare
technology assessment.
PMID- 10185996
TI - Where in the world are the ambulatory benchmarking data?
AB - If you haven't already been forced to take a hard look at your ambulatory care,
increasing payer and patient pressures mean you'll have to soon. Ambulatory care
accounts for more than half of U.S. health expenditures and could account for
half of average hospital revenue by the year 2000. The most difficult data to
find is on physician offices but several proprietary databases offer that
information, and a new project from the Accreditation Association for Ambulatory
Health Care will focus on collecting it. Some free data are available from state
and federal sources, but are not very current, not adjusted in any way, and may
take you a while to receive.
PMID- 10185997
TI - Academic clinics share best practices.
PMID- 10185998
TI - October conference will showcase best practices.
PMID- 10185999
TI - Do California trends foreshadow national ones?
AB - Take a look at what's in California's future, and maybe yours as well, through
the California Healthcare Association's recently released report, California
Health Care 1998-2005: View of the Future. Key themes in this year's report
include incremental health care reform, expanded access to health care coverage
for the uninsured, purchasers refocusing on price and quality, and integration in
rural health care. Preferred provider organizations will regain popularity, and
fewer physicians will remain in solo practice.
PMID- 10186000
TI - Finally: best practices available for obesity.
AB - The National Heart, Lung, and Blood Institute's new obesity guidelines urge
providers to treat obesity as a chronic disease. The guidelines address fen/phen
and other drugs as well as a whole host of issues that should be considered in
assessing obesity and managing weight. A program to change lifestyle habits
requires behavior modification and frequent contact between physicians and
patients.
PMID- 10186001
TI - Callaway Foundation, Network of Trust win first-ever GHA Leadership Awards.
PMID- 10186002
TI - A dose of reality.
PMID- 10186003
TI - DOJ and OIG issue guidance on False Claims Act.
PMID- 10186004
TI - Community Decision Making for Health Program.
PMID- 10186005
TI - Complaining counts.
PMID- 10186006
TI - Stats & facts. Has managed care helped contain health costs? The public's
perspective.
PMID- 10186007
TI - Web-based applications to reduce costs and improve patient care.
PMID- 10186008
TI - A conversation with John E. Ware, Jr., PhD.
PMID- 10186009
TI - Health-related quality-of-life measures in disease management programs.
PMID- 10186010
TI - Preventing medication-related problems among older Americans.
AB - This article provides an overview of the Fleetwood Project, a major three-phase
research and demonstration initiative to: (1) evaluate how consultant pharmacist
services influence health outcomes and costs by reducing medication-related
problems in long-term care settings, (2) compare outcomes from federally mandated
drug regimen reviews to prospective reviews and formalized pharmaceutical care
planning (the Fleetwood Model) for nursing facility residents at highest risk for
medication-related problems, and (3) apply and evaluate this model in a national
sample of nursing and assisted-living facilities.
PMID- 10186011
TI - Tapping the savings from vitamin-based prevention.
AB - Published scientific studies show that perinatal consumption of multivitamins
containing folic acid and zinc can significantly reduce the risks of low
birthweight, premature births, spina bifida, and cardiovascular birth defects.
Daily intake of vitamin E supplements reduces the risk of coronary heart disease
in older Americans. The authors believe that if all at-risk Americans took the
recommended amounts of vitamin supplements, significant numbers of
hospitalizations for these conditions could be avoided, and the managed care
industry could save approximately $5.5 billion, using 1995 figures.
PMID- 10186012
TI - The planning difference. Transitional versus change management.
PMID- 10186013
TI - Root cause analysis. A tool for understanding why accidents occur.
PMID- 10186014
TI - Renovation benefits residents with Alzheimer's at Silverado Senior Living.
PMID- 10186015
TI - The challenge of cyberspace. Human resource issues and policies in the high-tech
health care workplace.
PMID- 10186016
TI - A delegation of care. People to People Ambassador Programs.
PMID- 10186017
TI - Unleashing staff productivity.
PMID- 10186018
TI - Challenge the change myths.
PMID- 10186019
TI - Managing the stress that comes with organizational change.
PMID- 10186020
TI - 10 common Web page frustrations and how to cure them.
PMID- 10186021
TI - The requisite ingredient.
PMID- 10186022
TI - Marketing the long-term care facility.
PMID- 10186023
TI - Opportunity knocks. Prospective payment for skilled nursing facilities.
PMID- 10186024
TI - Consolidated billing. PPS and services furnished "under arrangement".
PMID- 10186025
TI - Improving nursing home residents' function and quality of life.
PMID- 10186026
TI - Cultivating media relations.
PMID- 10186027
TI - Change demands clarity, information & rewards.
PMID- 10186028
TI - Position your organization for health care reform.
PMID- 10186029
TI - Rules or roles--how do you lead?
PMID- 10186030
TI - HCFA begins efforts to revamp nursing home regulatory process.
PMID- 10186031
TI - Meeting the psychosocial needs of terminally ill patients.
PMID- 10186032
TI - Hospitals 'talking trash' to cut costs, help environment.
PMID- 10186033
TI - Even in best-run centers, preventable medication errors lengthen LOS, increase
costs.
AB - Preventing adverse drug events. Adverse drug events aren't always fatal, but they
invariably add to length of stay and health care costs. Boston researchers
estimate that adverse drug events cost a 700-bed teaching hospital about $5.6
million annually, $2.8 million of which is preventable. Albany Medical Center
looked closer at factors that contribute to adverse drug events, putting in place
a medication error detection program that prevented 2,100 errors in one year.
PMID- 10186034
TI - Networking via wireless bridge produces greater speed and flexibility, lowers
cost.
AB - Wireless computer networking. Computer connectivity is essential in today's high
tech health care industry. But telephone lines aren't fast enough, and high-speed
connections like T-1 lines are costly. Read about an Ohio community hospital that
installed a wireless network "bridge" to connect buildings that are miles apart,
creating a reliable high-speed link that costs one-tenth of a T-1 line.
PMID- 10186035
TI - Frequency-hopping technology permits patient monitoring away from costly ICUs.
PMID- 10186036
TI - Image-guided dialysis access ports more successful, less costly than surgery.
AB - Percutaneous dialysis catheters. Interventional radiologists can implant dialysis
catheters quicker and more reliably than vascular surgeons, which can translate
into big savings. A study from Yale University suggests that surgical dialysis
sites may cost three times as much as percutaneous devices.
PMID- 10186037
TI - Beware the promises of disease management companies when negotiating contracts.
PMID- 10186038
TI - Lateral transfer device reduces back injuries that result from moving patients.
PMID- 10186039
TI - Innovative program helps improve management of ADHD patients.
AB - Attention deficient hyperactivity disorder can baffle the parent, the physician,
and the health care delivery system as well. But one provider established a team
based, episodes of care approach to managing pediatric patients with this
disorder. Find out how the program might work for your patients.
PMID- 10186040
TI - DM programs take advantage of new therapies to reduce costs, complications for MS
patients.
AB - Multiple sclerosis patients can benefit from new drugs that slow the progression
of the disease, but only a fraction (20%) actually receive these drugs. A
specialty DM firm has found a way to enhance medication management and assist
patients in keeping debilitating complications at bay.
PMID- 10186041
TI - Diagnose Alzheimer's early and reap clinical, cost benefits.
AB - Alzheimer's Disease is a growing problem for physicians, who are often confused
about just how to diagnose and manage the disease in the context of the patient's
other cormorbidities. Here's a simple five-minute exam that will lead to earlier
diagnosis and more effective treatment.
PMID- 10186042
TI - Get ready for population-based disease management.
PMID- 10186043
TI - Specialty wound care centers heal where all else fails.
PMID- 10186044
TI - Home visits with first-time moms enhance self-care and improve birth outcomes.
AB - A nurse model home visitation program for low-income, first-time mothers is
decreasing the rate of future child abuse, preterm delivery, low-birth weight,
and pregnancy-induced hypertension. Find out how this intensive model of one-on
one education and self-care is making a difference.
PMID- 10186045
TI - New technology offers 'real time' picture of patients' status.
AB - Health plans are seeing their patients "face to face" on a daily basis in this
new age "virtual reality" population management program. Find out how several
health plans are benefitting from a program that provides unique insight into
their members' needs.
PMID- 10186046
TI - Predict utilization and get more bang for your DM dollars.
AB - Claims data is not the only way to target patients for a disease management
program. A new decision support tool is being used by some providers to assess
potential high utilizers of care. The tool also identifies possible demand
management interventions that may make a difference.
PMID- 10186047
TI - Risk contractors take aim at skyrocketing drug costs.
PMID- 10186048
TI - New software provides tool for managing contact capitation.
AB - The main drawback to contact capitation has been its administrative complexity.
Now, a San Francisco managed care firm has released an Internet-based system that
offers a simple process for determining contact values and payment amounts.
PMID- 10186049
TI - New models of capitation continue to emerge in effort to reduce variability.
AB - As a reimbursement mechanism for specialty care, contact capitation has received
the most play, but other payment mechanisms that shift all or a portion of the
risk associated with specialty care are emerging.
PMID- 10186050
TI - Attractive capitation rates can't salvage group with faulty compensation
structure.
PMID- 10186051
TI - Create a comfort zone when negotiating your cap rate.
AB - The ability of a physician or medical group to determine an affordable payment
level is a cornerstone of effective capitation contracting. That process doesn't
always require expensive actuarial analysis.
PMID- 10186052
TI - Marketplace. Systems quality measurement consortium adapts to new marketplace
realities.
PMID- 10186053
TI - Perspectives. Physician performance measurement initiatives gain ground.
PMID- 10186054
TI - Perspectives. Shortage amid plenty complicates task of redefining underserved
areas.
PMID- 10186055
TI - Perspectives. Use of telemedicine for home care ripe for experiment.
PMID- 10186056
TI - Automatic couriers revolutionize material transport at U.S. hospitals.
PMID- 10186057
TI - Do you want to please your patients?
PMID- 10186058
TI - Redesign challenge lies in making it stick.
PMID- 10186059
TI - Taking on more means letting the details go.
PMID- 10186060
TI - Sharpen your pencils to survive managed care, PPS.
PMID- 10186061
TI - Comprehensive management, clinical software produce 'paperless' office.
PMID- 10186062
TI - Liaisons lend sanity to merger madness.
PMID- 10186063
TI - Learning from industry: best practices for mergers.
PMID- 10186064
TI - Novel strategies decrease ED delays.
PMID- 10186065
TI - Cancer center revives staff orientation to focus on service.
PMID- 10186066
TI - Orientation jump-starts employees on PFC.
PMID- 10186067
TI - Redesign improves admissions system.
PMID- 10186068
TI - Employees empowered to handle patient complaints.
PMID- 10186069
TI - Hospital links substance abuse patients, treatment.
PMID- 10186070
TI - Trauma centers strong financial contenders.
PMID- 10186071
TI - A provider-sponsored victory. Hospitals pleased with negotiated PSO solvency
standard.
PMID- 10186072
TI - Service excellence: more than a mantra.
PMID- 10186073
TI - The operative word is "future".
PMID- 10186074
TI - Getting better all the time. Systems redefine outcomes and the quest for health
care quality.
PMID- 10186075
TI - A boost for women's health research.
PMID- 10186076
TI - Hospital war averted over wage index controversy.
PMID- 10186077
TI - HCFA delays enforcement of organ procurement rules.
PMID- 10186078
TI - A conversation with ... Robert Berenson, M.D., Director, Center for Health Plans
and Providers, HCFA.
PMID- 10186079
TI - Home health agencies: 'new' becomes 'old' for reimbursement purposes.
PMID- 10186080
TI - Successful compliance officers must understand hospital decision-makers.
PMID- 10186081
TI - COBRA's bite--is it getting worse?: an analysis of HCFA's guidelines on patient
dumping.
PMID- 10186082
TI - When you wish upon a Starr.
PMID- 10186083
TI - Congress: keep focus on health care despite distractions.
PMID- 10186084
TI - Practical solutions to boost adult and childhood immunization rates.
PMID- 10186085
TI - A diabetes DM program built on empowerment.
PMID- 10186086
TI - Pathways lead to better management of asthma.
PMID- 10186087
TI - Something old; something new in asthma care.
PMID- 10186088
TI - What's squeezing out capitation in the land of HMOs?
PMID- 10186089
TI - PPMs have a future, but role is murky.
PMID- 10186090
TI - Maintaining market share: competing ventures work together.
PMID- 10186091
TI - Colorado health plans collaborate on guidelines.
PMID- 10186093
TI - Picking the right managed care software.
PMID- 10186092
TI - Leveraging a negotiating position.
PMID- 10186094
TI - Physician bonus programs reward patient satisfaction.
PMID- 10186095
TI - Beth Israel and Deaconess merger: an all-at-once effort.
PMID- 10186096
TI - Physician practices not bargain some buyers expected.
PMID- 10186097
TI - Providers confront challenges in HMO contracting.
PMID- 10186098
TI - Healthcare systems tap various tools to keep customers happy--and enrolled.
PMID- 10186099
TI - Outsourcing firms expand services to meet healthcare's demands.
PMID- 10186100
TI - Assembly line system streamlines records department, prepares for EMR.
PMID- 10186101
TI - Patterns emerging in HMOs experiencing problems.
PMID- 10186102
TI - Slapping on a label can turn a brand into a scarlet letter.
PMID- 10186103
TI - Biggest cost in credentialing comes from failure to do it right.
PMID- 10186104
TI - Virtual integration sidesteps merger headaches.
PMID- 10186105
TI - Relieving physicians' stress aids retention, improves care.
PMID- 10186106
TI - Employee satisfaction drives employers' health plan choices.
PMID- 10186107
TI - Better reporting, forms and procedures reduce medication errors.
PMID- 10186108
TI - Community pharmacists need information to be effective care team members.
PMID- 10186109
TI - Hospitalists reducing cost of hospital care.
PMID- 10186110
TI - Assisted living offers market for providers and control for MCOs.
PMID- 10186111
TI - Pharmaceutical risk sharing may cut losses, but is unlikely to produce gain.
PMID- 10186112
TI - The effect of a compliance program in the health care industry.
PMID- 10186113
TI - The Stark Act--joint ventures.
PMID- 10186114
TI - Physician's antitrust complaint dismissed for failure to show antitrust injury.
Ramey v. Pacific Foundation for Medical Care.
PMID- 10186115
TI - Qui tam action against intermediary dismissed. U.S. Ex. Rel. Body v. Blue Cross &
Blue Shield Alabama.
PMID- 10186116
TI - Original source decision further restrains qui tam litigation. U.S. ex rel Lance
Haafter and George Schwartz v. Spectrum Emergency Care, Inc., et al.
PMID- 10186117
TI - Recent trends in physician practice acquisitions: a focus on value and
compliance.
PMID- 10186118
TI - Deputy Attorney General issues guidance for enforcement of False Claims Act.
PMID- 10186119
TI - Physician practice compliance plans: 50,009 reasons to have one.
PMID- 10186120
TI - The asymptomatic ill and genetic discrimination. Part II.
PMID- 10186121
TI - The OIG's model compliance program.
AB - Home care agencies face never-ending and hard-to-track list of rules. The Office
of the Inspector General has provided guidelines for agencies on implementing a
voluntary compliance program to prevent fraud, abuse, and waste. Through the
development of internal controls, which promote adherence to federal and state
laws, agencies safeguard themselves from problems.
PMID- 10186122
TI - Home care compliance: how to protect yourself.
AB - Home care agencies are operating in a supercharged environment of distrust,
thanks to recent regulatory and legislative changes. By establishing and closely
following compliance programs, however, they will lower their risk and make
improvements in overall agency operations.
PMID- 10186123
TI - A practical guide to creating compliance programs.
AB - Regardless of size or corporate structure, all home care agencies will feel the
heavy hand of the government's efforts to detect fraud and abuse in health care.
By preparing ahead of time, agency owners can be confident that any investigation
will have a satisfactory conclusion.
PMID- 10186124
TI - The new verification audit. Are you ready?
AB - To successfully withstand a verification audit, agencies should be prepared for
the worst case scenario--the suspension of payments without notice. Ample
preparation for the possibility of these audits will place agencies in the best
position to navigate these difficult waters smoothly.
PMID- 10186125
TI - Sentinel events: policy & preparation.
AB - Accreditation by the Joint Commission on Accreditation of Healthcare
Organizations (JCAHO) is a sign of quality. Now JCAHO is increasing the
stringency of its requirements by addressing sentinel events. Organizations--both
home care providers and facilities--need to understand what a sentinel event is
and how it affects accreditation status. Policies established to address these
events will help home care providers maintain and/or improve the quality of the
care they provide.
PMID- 10186126
TI - Admission and termination policies. Minimizing risk and liability.
AB - Changes in Medicare reimbursement coupled with the demands of managed care plans
to reduce resource utilization continue to challenge patient management in home
care. As home care agencies endeavor to achieve optimal outcomes with reduced
resources, professional liability exposures may increase. Agencies should protect
themselves using sound admission, care management, and discharge policies, as
well as other risk management options.
PMID- 10186128
TI - The critical role of social work in risk management.
AB - If they are included in cases early enough, social workers can help agencies
manage risk, protect patients, and avoid litigation. These professionals offer
unique skills that agencies should tap into more consistently to reap the
benefits of better risk management.
PMID- 10186127
TI - Telehomecare rewards and risks.
AB - Telehomecare offers improved access to home care at lower costs and promises
unique opportunities for home care patient empowerment and improved care
outcomes. Telehomecare programs must be carefully designed to comply with
licensure requirements, minimize liability risks, protect patient privacy, and
capitalize on reimbursement trends. Providers willing to invest in the
development of well-designed telehomecare programs and to document the merits of
their initiatives should be well-positioned to serve the country's aging
population under any of the care models that will dominate health care delivery
in the next century.
PMID- 10186129
TI - Sexual harassment liability & disability discrimination: new rules apply.
AB - Recent decisions by the Supreme Court give some indication of how a court would
rule in a sexual harassment or disability discrimination suit. Home care
providers need to understand the effect of these rulings and ensure that their
own policies are clear and clearly disseminated to employees.
PMID- 10186130
TI - Getting heart patients to the hospital quickly.
AB - Agencies that care for patients at high risk of acute myocardial infarction may
be interested in a new study by the National Heart, Lung, and Blood Institute
that describes this high-risk population and details steps providers can take to
assist them.
PMID- 10186131
TI - Legal issues/emotional issues: the other side of litigation.
PMID- 10186132
TI - Cancel IPS.
PMID- 10186133
TI - The right stuff. Meet the winner of the 1998 EMS Magazine/Braun Industries'
EMT/Paramedic of the Year Award.
PMID- 10186134
TI - Principles of emergency vehicle placement.
PMID- 10186135
TI - Curing those dealership blues.
PMID- 10186136
TI - Learning to drive ... all over again. Florida subcommittee revamps training
guidelines for ambulance drivers.
PMID- 10186137
TI - Warn them with radar.
PMID- 10186138
TI - Buckle up! Kicker Vest Attendant Restraint System protects providers.
PMID- 10186139
TI - Ambulance dealership listing. Part II.
PMID- 10186140
TI - EMS incident management: the safety sector.
PMID- 10186141
TI - Hazardous waste management review.
PMID- 10186142
TI - Work in healthcare ... are you ready for the challenge?
PMID- 10186143
TI - What really goes on in your doctor's office?
AB - Hate managed care? It's no picnic for doctors either. The big question is whether
medicine's new order is making your doc treat you better or worse.
PMID- 10186144
TI - Seven spoonfuls of preventive medicine for sexual harassment in health care.
AB - Sexual harassment claims have increased substantially since 1990 and continue to
be prominent in the Equal Employment Opportunity Commission's discrimination
caseload. The authors surveyed high-level training and human resource
practitioners in small, medium, and large health care organizations for
suggestions to counter this trend. Three fourths of these professionals suggested
that behavior modeling of strong policies combined with effective training
helped. The survey results suggest seven preventive medicine strategies for
reducing work-related sexual harassment incidents in health care organizations.
PMID- 10186145
TI - Recognizing abuse in culturally diverse clients.
AB - Abuse is a major problem in American society. The problem of abuse among
ethnically diverse persons is an area about which most health care professionals
know little. This article describes the Giger-Davidhizar Model of Transcultural
Assessment as a tool of assessment of the client who is abused. Use of a
framework for assessment can enable more culturally competent care to be
delivered.
PMID- 10186146
TI - Workplace privacy: HIV testing, disclosure, and discrimination.
AB - Human immunodeficiency virus (HIV) testing and the disclosure of HIV-related
information pose questions of privacy and public policy that are of concern in
both public- and private-sector workplaces. Public-sector employees have
constitutional protection from discrimination on the basis of their HIV-positive
status. The Americans with Disabilities Act (ADA) is an important source of
protection for private-sector employees. There are also other federal laws that
provide protection from discrimination. However, the scope of these laws is
unclear. Similarly, while some state legislatures have attempted to set standards
to protect the privacy of HIV-positive employees, laws vary from state to state.
Case precedent is also inconsistent. This article examines some current issues
regarding HIV testing, employee privacy, and protection from discrimination.
PMID- 10186147
TI - Time-bound madness.
AB - The concept of the passage of time is familiar to most people regardless of
ethnic heritage. However, some persons are more time-bound than others. This
article discusses the qualities of time-bound individuals and outlines strategies
for responding to time-bound madness.
PMID- 10186148
TI - Developing a mission statement for self and family.
AB - What would you like people to say about you at your wake? Your answer to that
question provides a strong clue about what your personal mission statement should
include. It may also inspire you to draft such a document. If it does, you may
find some helpful suggestions in this article.
PMID- 10186149
TI - Medical outcomes assessment and management with emphasis on laboratory
applications.
AB - Outcomes assessment and management are playing an increasing role in reducing
costs and providing better customer satisfaction. In this overview we describe
some outcomes applications and techniques, including benchmarking and clinical
pathways. Some outcomes undertakings are complicated and may be frustrating, but
most are rewarding to patients or health care providers or both. Challenges are
discussed and laboratory applications featured.
PMID- 10186150
TI - Mixed motivations: the leadership contradiction.
AB - Individuals who seek leadership positions are driven by a mixture of motivating
forces that involve the pursuit of largely psychological needs that are often far
more self-serving than altruistic. Because of personal drives involved, we have
reason to conclude at times that the leaders we do get are not the best, because
the truly best are not strongly driven to seek leadership. Also, supervisors and
other managers frequently make the mistake of judging employees' drives and
motivations differently from their own. However, followers follow for the same
essential reason that leaders lead: to attain need satisfaction. There are
various patterns or styles of leadership, and it is possible to readily identify
a particular leader's style and to learn something about the needs that drive the
leader simply by observing that person's behavior. Ultimately the leaders who are
most successful are those who are able to make the organization's goals their own
and to be genuinely driven to attain those goals.
PMID- 10186151
TI - A supervisor asks: "the employee and the job".
PMID- 10186152
TI - Using fingerprints to improve patient sign-in, identification.
PMID- 10186153
TI - Emergencies involving children: how they were handled at three hospitals.
PMID- 10186154
TI - Hospital, consultant plan security strategy for future parking expansion.
PMID- 10186156
TI - New generation of intercoms for hospital security speeds response times.
PMID- 10186155
TI - International patients: a different market with different security needs.
AB - Different customs ... language barriers ... unfamiliarity with this country.
These problems of foreign patients and the visitors that accompany them can be
also cause problems for hospital security departments--especially those who fail
to prepare for this growing healthcare market. According to recent articles in
leading publications, the immigration boom, continuing demographic shifts in
urban America, and an influx of hospital marketing campaigns aimed at affluent
foreign clients have more and more healthcare organizations involved in trying to
bridge the culture gap. In this report, we'll give details on how five major
hospitals that actively seek foreign patients are organized to meet their
security needs and relate what happened when a foreign celebrity unexpectedly
became a patient at a county hospital.
PMID- 10186157
TI - 1998 salary survey results. Are your peers living fat, or scraping by?
PMID- 10186158
TI - As CON laws disappear, quality becomes more important in decisions.
PMID- 10186159
TI - PA's in the 'wild, wild west for cardiac surgery'.
PMID- 10186160
TI - NJ regs impose volume requirement for credentials.
PMID- 10186161
TI - Ohio: 'an extraordinary glut of capacity'.
PMID- 10186162
TI - Plan for data collection.
PMID- 10186163
TI - Home alone: unmet need for formal support services among home health clients.
AB - In order to remain in the home without family or other informal support, home
health clients must have access to essential formal services such as nutritional
support and homemaking chores to supplement medical and nursing care. In this
study, we looked at client-related factors associated with the need for formal
support services, and factors associated with whether those needs are adequately
met. Data were collected from 2,013 home health clients in Massachusetts.
According to the assessment of the skilled nurses treating them, 85 percent of
the clients needed one or more support services; some or all needs were not
adequately met in nearly half. Significant factors contributing to unmet need
included: being non-white, having Medicaid as payer, being in a health
maintenance organization, having AIDS, receiving maternal/child health services,
and having an acute condition. This research suggests that even clients receiving
skilled nursing care may not have many or most of their supportive needs met, and
that there are identifiable factors which decrease the likelihood of having
adequate care provided.
PMID- 10186164
TI - Older home health care patients and their physicians: assessment of functional
ability.
AB - Assessment of a person's level of functional impairment is a key aspect of
geriatric clinical practice. This study examines the agreement between functional
assessments reported by 54 physician-patient dyads. Physicians were typical of
those providing services to elderly patients in an urban area. Patients, all aged
65 or more years and community-living, had been referred by these physicians for
in-home health care services. Generally, physicians reported less impairment than
did their patients, functional assessments by both doctors and patients matching
completely in only 15 of 54 (28%) dyads. Underestimation of patient impairment
occurred most commonly with respect to stair climbing, control of the urinary
bladder, and bathing, but was also substantial for dressing, walking, and
toileting. Few patient or doctor characteristics predicted congruence or lack
thereof in assessment of functional impairments. Some implications of these
findings for clinical practice and medical education are examined.
PMID- 10186165
TI - Falls of elderly rural home health clients.
AB - This study examined factors related to falls among elderly home health clients
living in rural southern Illinois. Forty-five clients who fell were
demographically matched with 45 controls. Logistic regression analysis revealed
that previous falls, frailty, physical inactivity, balance problems, absence of
handrails, and uneven floors were related to a fall in this sample. Medications
commonly taken by clients were not found to be related to a fall, whereas
environmental factors appeared to contribute to a fall. Elderly home health
clients need information and support services to recognize risk of falling and
encourage preventive measures such as physical therapy and environmental
modifications.
PMID- 10186166
TI - Factors influencing the use of adult day care by individuals with Alzheimer's
disease: a multivariate examination of the California Alzheimer's Disease
Diagnostic and Treatment Center Program.
AB - Longitudinal data from the California State Alzheimer's Disease Diagnostic and
Treatment Center Program (ADDTC) are analyzed to determine what factors,
including ADDTC staff recommendations for service use, influence utilization of
adult day care services by individuals with Alzheimer's disease. The records of
737 clients are examined from 1988 to 1992 to determine predictors of client
service utilization (including client predisposing, enabling, and need
characteristics; caregiver characteristics; and community characteristics).
Results of logistic regression analyses indicate that ADDTC staff recommendations
and previous use of adult day care services are significantly related to use of
adult day care services. Other client predisposing, enabling, and need
characteristics; caregiver characteristics; and community characteristics were
not significantly related to service use.
PMID- 10186167
TI - Home-care workers: work conditions and occupational exclusion: a comparison
between carers on early-retirement and regular pensions.
AB - The aim of the study was to identify conditions associated with occupational
exclusion from home-caring. In a group of 346 home-care workers who responded to
a questionnaire, there were 18 newly-retired carers on early
retirement/disability pensions, and 28 carers who had just taken regular
retirement. A discriminant analysis was conducted to identify work conditions
that differentiated the two groups. The results show that a combination of
variables--functional impairment (pain when doing physical work), psychosomatic
complaints, and nature of relationship with/attitude to clients--significantly
differentiated the two groups. When the discriminant coefficients were applied to
other groups--older full-time and part-time employees (n = 224), carers who had
undergone job transfers, and carers on long-term sick leave--the order of groups
by discriminant-point score was largely as expected. The results are discussed in
relation to dilemmas, psychological demands and organizational circumstances
prevailing in home-care work.
PMID- 10186168
TI - Workforce planning. Catching the drift.
AB - NHS workforce planning has traditionally ignored the role of doctors and nurses
trained in continental Europe and Scandinavia. At present doctors trained in the
European Economic Area make up 10 per cent of senior house officers in England
and Wales. But the numbers coming to the UK are falling. Falling medical
unemployment in Europe will mean these doctors have less incentive to come to the
UK, leaving a considerable gap in the NHS workforce. More local research is
needed into working patterns and career plans of European-trained nurses and
doctors.
PMID- 10186169
TI - NHS careers. In the blood.
PMID- 10186170
TI - Transport. Traffic warning.
PMID- 10186171
TI - Site redevelopment. Work in progress.
PMID- 10186172
TI - Private finance: buildings. Best of the bunch.
PMID- 10186173
TI - Private finance: equipment. Off the books.
PMID- 10186174
TI - Primary care groups. View to a skill.
AB - Training is of critical importance to the successful development of PCGs. There
are particular needs for developing strategic planning capacities. PCGs will need
to understand and adopt many public health skills.
PMID- 10186175
TI - Health promotion. Beating the bands?
AB - A survey of health authorities in England to establish GPs' health promotion
activities found that anti-smoking and heart disease prevention were the most
common initiatives. Many HAs were dissatisfied with the current arrangements,
feeling that they had little control of GPs' health promotion activities. Two
thirds of HAs reported problems with monitoring GPs' health promotion activities.
Few health promotion initiatives addressed mental health, cancer or accident
prevention.
PMID- 10186176
TI - US healthcare. The big grapple.
PMID- 10186177
TI - Career profile. Changing paces.
PMID- 10186178
TI - Reflections on ASCO (American Society of Clinical Oncologists).
AB - As life expectancy increases and the population ages, people become more
susceptible to degenerative diseases such as cancer. This has wide-ranging
implications for cancer care, a specialty that has historically been underfunded
and under-resourced in the UK. Dr. Martin Duerden, who canvassed the opinions of
UK oncologists at the American Society of Clinical Oncologists' conference in Los
Angeles earlier this year, focuses on the provision of chemotherapy in the
context of the latest evidence and considers the implications for cancer care in
a changing NHS.
PMID- 10186179
TI - NHS ombudsman. The fixer.
PMID- 10186180
TI - NHS ombudsman. A job for strife.
AB - The commissioner's office investigates only about 4 per cent of the complaints
received. The average time taken for an investigation is 45 weeks. The impact of
the commissioner's work on the NHS is difficult to establish.
PMID- 10186181
TI - Medicines management. NICE (National Institute for Clinical Excellence) but not
easy.
PMID- 10186182
TI - Data briefing. Performance indicators.
PMID- 10186183
TI - Primary cares. Messages from the frontline.
AB - The biggest hurdle in the establishment of primary care groups is practices'
reluctance to co-operate. GPs will want compensation for the time spent on
administration. There is little awareness of the fact that PCG budgets may run
out. The development of PCGs is expected to lead to an increase in salaried GPs.
Current IT systems are seen as inadequate for PCGs.
PMID- 10186184
TI - Heading for Reading.
PMID- 10186185
TI - Primary care. Phoney wars.
PMID- 10186186
TI - Community hospitals. Delivering the goods.
PMID- 10186187
TI - Occupational health. Off the hook.
PMID- 10186188
TI - Healthy living centres. Centre stage.
PMID- 10186189
TI - Information technology. Burned out.
PMID- 10186190
TI - Collaborative working. Creaking joints.
PMID- 10186191
TI - Buildings. Supermodels in practice.
PMID- 10186192
TI - Working hours. Minute stakes.
AB - The working time directive has major implications for NHS employers. Many NHS
employers believe current systems for recording hours worked will not meet the
directive's requirements. The introduction of leave entitlement for bank and
agency nurses is likely to cost the NHS an extra 40 m Pounds or more a year. The
directive does not currently apply to junior doctors. But if, as expected, they
are brought within it, the implications for the NHS are huge.
PMID- 10186193
TI - Primary care groups. Growing pains.
AB - The management costs of primary care groups are likely to be higher than
envisaged. Duplication of all functions in all PCGs is likely to be more
expensive than current health authority commissioning arrangements. In the long
term, the most effective deployment of management costs will depend on deciding
which PCG commissions what.
PMID- 10186194
TI - Data briefing. Hospital beds.
PMID- 10186195
TI - Organisations. Knowing who's boss.
AB - A hierarchical structure in organisations reflects the natural order. A hierarchy
does not have to denote an authoritarian management style. People need to know
who their boss is. Lines of accountability on many hospital wards are unclear.
PMID- 10186196
TI - Human resources. Own goal.
PMID- 10186197
TI - Waiting lists. On a knife edge.
AB - Achieving the government's waiting list targets relies heavily on the willingness
of theatre staff to do overtime. A survey of acute trusts in England found that
more than three-quarters were having difficulty recruiting staff. A third were
using local pay incentives, including double time for waiting list initiative
work and bonus schemes. Theatre management needs a more strategic approach.
PMID- 10186198
TI - Prescribing. Reverse charges.
PMID- 10186199
TI - Finance. In sickness and in wealth.
PMID- 10186200
TI - Key industry facts. American College of Healthcare Executives.
PMID- 10186201
TI - Ensuring board effectiveness: it could be as simple as changing your board
structure.
PMID- 10186202
TI - The changing role of the COO.
PMID- 10186203
TI - Rumors of unethical conduct.
PMID- 10186204
TI - Recognizing and avoiding burnout.
PMID- 10186205
TI - Physician board members.
PMID- 10186206
TI - The physician payment rule.
PMID- 10186207
TI - A balance of skills. Skills required for success differ at each stage in your
career.
PMID- 10186208
TI - Measuring the needs of the Medicare population.
PMID- 10186209
TI - Putting information technology to use.
PMID- 10186210
TI - Marketing on the Internet.
PMID- 10186211
TI - Preventing board-community disconnect.
PMID- 10186212
TI - Hot jobs for the year 2000.
PMID- 10186213
TI - Smooth soaring. The ride to career success can be a bumpy one. Here are six ways
to avoid turbulence along the way.
PMID- 10186214
TI - Appointing an ethics officer.
PMID- 10186215
TI - Is it time to change jobs?
PMID- 10186216
TI - Incentive-based compensation.
PMID- 10186217
TI - Medicare+Choice regulation.
PMID- 10186218
TI - Progress depends on responsiveness.
PMID- 10186219
TI - Quality connections on the Internet.
PMID- 10186220
TI - Securing information on the Internet.
PMID- 10186221
TI - Balancing stakeholder satisfaction.
PMID- 10186222
TI - Boomers vs busters. Addressing the generation gap in healthcare management.
PMID- 10186223
TI - Skill mix changes: substitution or service development?
AB - An extensive review of published studies where doctors were replaced by other
health professions demonstrates considerable scope for alterations in skill mix.
However, the studies reported are often dated and have design deficiencies. In
health services world-wide there is a policy focus which emphasises the
substitution of nurses in particular for doctors. However, this substitution may
not be real and increased roles for non-physician personnel may result in service
development/enhancement rather than labour substitution. Further study of skill
mix changes and whether non-physician personnel are being used as substitutes or
complements for doctors is required urgently.
PMID- 10186224
TI - Economic evaluation of screening for prostate cancer: a randomized population
based programme during a 10-year period in Sweden.
AB - Prostate cancer is a growing health problem representing considerable costs.
Screening and early curative treatment may reduce morbidity and possibly prevent
future escalating costs. However, population screening programmes are generally
not well accepted at present due to uncertainty about whether screening for
prostate cancer can result in reduced mortality. Evidence from large, randomized,
controlled trials is still lacking. The objective of this study was to calculate
clinical and economic consequences of general prostate cancer screening based on
a limited screening trial in a Swedish community and a decision-tree model. A
random selection of 1492 men (50-69 years) were invited to repeated screening in
1987. They have been examined every third year (four rounds). The other 7679 men
in the population act as controls. The results show that the total incremental
health care costs for prostate cancer will increase by 179 million SEK per year
with screening compared to no-screening. The number of detected cases of
localized cancer will increase by about 1000, which represents an additional cost
of about 158,000 SEK per case. In conclusion, general screening for prostate
cancer can be performed with a reasonable cost per detected localized cancer.
Information on the long-term effect on life quality and cancer mortality is
unknown.
PMID- 10186225
TI - Diffusion of laparoscopic technologies in Denmark.
AB - It has been predicted that minimally invasive therapy will have dramatic
consequences for the specialty of general surgery, as demonstrated by the
diffusion of laparoscopic cholecystectomy. To investigate the determinants of the
diffusion in Denmark of five laparoscopic technologies (cholecystectomy,
appendicectomy, surgery for colon cancer, surgery for inguinal hernia and
fundoplication), questionnaires on seventeen factors' influence on the adoption
(stimulating or impeding) were sent to fifty-nine hospitals. Fifty hospitals
(85%) responded. Overall, 98% adopted laparoscopic cholecystectomy in Denmark
between 1991 and 1995, whereas the remainder of the technologies were adopted by
7-65% of hospitals performing these operations. Large and specialized hospitals
were the earliest adopters. The factors, nature of technology (minimally invasive
versus conventional), training (appropriate training courses), competition
(between specialties and between hospitals) and media attention have stimulated
the diffusion, whereas three budget factors (budget for investment, budget for
operation and public regulation) usually had an impeding effect. Stimulating
factors prevail for all laparoscopic technologies indicating that some guidance
of the adoption and use of new health technologies might be necessary. In
Denmark, one of the suggested health policies to secure timely guidance is the
establishment of an early warning system.
PMID- 10186226
TI - Risks and benefits of private health care: exploring physicians' views on private
health care in Ho Chi Minh City, Vietnam.
AB - As in a number of other low- and middle-income countries, the health sector in
Vietnam is transforming with a rapid shift from fully state run and financed
health care towards more private financing and delivery of health care. This
development has been particularly noticeable in the largest city in the country,
Ho Chi Minh City, where a majority of physicians now are practising in private
clinics and where the private health care sector is an increasingly popular
option for people. While the private sector is an important part of the health
care system in Vietnam, few data are available on the characteristics and quality
of private health care services. This case study describes some aspects of the re
emerging private health care sector in Ho Chi Minh City, Vietnam, from the view
of 27 private and non-private physicians. The paper explores physicians' reasons
for going private, physicians' notions of patients' health care preferences, and
physicians' views on potential influence of financial incentives on
characteristics of private health care. The characteristics of private health
care are discussed in relation to a context of private health care characterised
by a fully patient-financed fee-for-service payment system, weak regulatory
mechanisms, and a public health care system (government-run and-financed health
care) that operates under resource constraints. Issues to consider when
attempting to steer private health care in Vietnam in a direction where it can
optimally contribute to public health, are discussed while considering the
interplay between authorised private practitioners, private pharmacies, the
informal private sector, and the public health care sector.
PMID- 10186227
TI - Evaluating the Israeli health care reform: strategy, challenges and lessons.
AB - Evaluating the implementation of health care reform provides important
information on its effect, as well as a factual basis for deciding upon mid
course modifications. Although researchers in various countries are addressing
the impact of reform, only few governments have initiated a structured, planned
evaluation to accompany reform efforts. In Israel, the 1995 National Health
Insurance Law earmarked 0.1% of the health care budget for research on the law,
coordinated by the National Institute for Health Policy and Health Services
Research. This paper describes the evaluation strategy of the JDC-Brookdale
Institute which is taking part in the research efforts. Implementation of the
evaluation strategy and the challenges of evaluating a major reform of the health
system are discussed. The evaluation strategy combines elements of formative and
summative evaluation using a 'case study' approach which seeks to integrate in
depth understanding of the changing health system and of health care provider's
organizational behavior, with a variety of outcome measures. The Israeli case
provides support for the proposition that an integrated approach to evaluating
health reform provides a better understanding of the subject under review and
thus a better basis for making useful recommendations to policy makers. In
addition, such an approach enhances the validity and credibility of the data and
thus the probability of making an impact, which is a main objective of formative
evaluation. Examination of the Israeli case, provides important insights about
evaluation of health system reform, and may benefit researchers in other
countries attempting to evaluate health care reform.
PMID- 10186228
TI - Supreme Court clears the way for parallel criminal and civil proceedings. Hudson
v. United States.
PMID- 10186229
TI - Federal court finds immunity under HCQIA. Rogers v. Columbia/HCA of Central
Louisiana.
PMID- 10186230
TI - Gown prices climb despite competition.
PMID- 10186231
TI - VA hospitals in good shape to head off Y2K troubles.
PMID- 10186232
TI - Household names can often deliver the goods.
PMID- 10186233
TI - Organizing specialty services: specialty hospitals within the hospital and
beyond.
PMID- 10186234
TI - The challenges and opportunities of laboratory regionalization.
AB - These are some of the major historical trends and rationale for the sea change in
laboratory medicine today. The creation of cooperative regional networks and
consolidated regional laboratories potentially can: 1) Pool the technologic
strengths of individual laboratories across a region; 2) Create economies of
scale by combining capacities for certain procedures; 3) Lower unit costs by
increasing volumes of business from nonpatients; 4) Span all of the traditional
testing venues along the new expanding continuum of care. The authors in this
monograph will take the saga forward in time, outlining critical organizational,
technologic, and strategic aspects of the newly evolving laboratory of the 21st
century.
PMID- 10186235
TI - Outsourcing: gaining strategic advantage through focus.
PMID- 10186236
TI - The medical records maze: a construct of federal inaction and state
inconsistency.
PMID- 10186237
TI - Structuring physician membership on the hospital governing board.
PMID- 10186238
TI - Negative financial incentives and ERISA's fiduciary obligations: a route around
preemption?
PMID- 10186239
TI - Revenue Ruling 98-15: dimming the future of all nonprofit joint ventures?
PMID- 10186240
TI - Proposed Stark II rules: clarification or more confusion?
PMID- 10186241
TI - Customer service key to quality management.
PMID- 10186242
TI - Maximizing fleet performance.
PMID- 10186243
TI - Do's and don'ts of ambulance specs. 10 things to consider when you spec a new
ambulance.
PMID- 10186244
TI - Powerful ambulances. A look at how generator-powered ambulances are charging up
the EMS industry.
PMID- 10186246
TI - 1998 ambulance manufacturers' directory.
PMID- 10186245
TI - Hip tools. Multi-purpose survival tools work their way into emergency scenes.
PMID- 10186247
TI - Stewardship and managed care.
PMID- 10186248
TI - A multi-attribute approach to segmenting the volunteer market for hospitals.
PMID- 10186249
TI - The role of psychographic characteristics as determinants of complaint behavior
by elderly consumers of physician health care services.
AB - The authors investigate the influence of various psychographic characteristics in
distinguishing between those elderly patients who complain about dissatisfying
experiences with health care providers and those who do not. Discriminant
analysis results suggest that patients who are low in trust in their physicians
and who are younger in terms of cognitive age are more likely to complain than
are patients who are high in trust and older in terms of cognitive age. In light
of these findings, the authors propose a number of managerially-relevant courses
of action for health care providers.
PMID- 10186250
TI - Assessing physician/patient relationships in the presence of HIV/AIDS: an
exploratory study.
AB - The following study investigates the nature of the relationship between
physicians and HIV/AIDS patients within the context of the rapidly evolving
services/relationship marketing literatures. The emerging evidence suggests that
service providers generally play a critical role in the development of positive
consumer attitudes and behaviors, and that relationship marketing practices can
contribute to the delivery of health services. However, to date, there appears
little evidence supporting the efficacy of employing relationship marketing
practices in relation to a target market of HIV/AIDS patients. This exploratory
study contributes to the body of knowledge by more closely investigating the
nature of the patient-physician relationship relative to HIV/AIDS patients'
attitudes, marketing-related behaviors, and overall quality-of-life/life
satisfaction judgments. The results of this study first suggest that HIV/AIDS
patients use the expectancy disconfirmation model when evaluating the performance
of their physician. A reliance on expectancy disconfirmation suggests the likely
prevalent role of service quality perceptions and satisfaction judgments in
evaluating their relationship with their physician. Second, the results appear to
support the conclusion that the patient's evaluation of their physician
relationship and subsequent behaviors (e.g., word-of-mouth) are directly related
to the patient's general perception of received health services. Thus, the
patient/physician relationship may play a particularly powerful role in
determining patient (marketing related) outcomes relative to other health service
settings. Third, a direct influence is supported between negative affective
reactions by patients and subsequent outcome behaviors. This finding lends
support for the potential efficacy of service recovery efforts when rendering
treatment to HIV/AIDS patients. Finally, evidence is presented demonstrating the
effect of positive perceptions of the patient/provider relationship on these
patients' overall evaluation of their quality-of-life/life satisfaction. The
managerial and research implications of this study are presented and discussed.
PMID- 10186251
TI - Medical outshopping intent: profiling the health care consumer.
AB - The health care industry has been exposed to a tremendous upheaval in the last
decade. The traditional practices have given way to new behaviors and structures.
This is especially true for community hospitals that have long provided the major
portion of health care services in their markets. Their traditional local service
area, once thought of as fairly much their sole domain, is being redefined.
Consumers are becoming more aware of alternative health delivery options, thus
choosing to go outside of their local trading area for these alternatives. This
study investigates consumer characteristics and influences driving this behavior.
Implications for hospital marketing practices are discussed.
PMID- 10186252
TI - Employee perceptions of 'profiled' customers' expectations.
AB - There has been an increasing interest in the issues of quality in service
delivery. The SERVQUAL theory addresses these issues and identifies the causes of
service quality problems. The practical, managerial implications of the SERVQUAL
theory and model are currently being addressed (Reidenbach and Sandifer
Smallwood, 1990; Woodside, Frey and Daly, 1989; Mangold and Babakus, 1991;
Webster, 1989; Day, 1992). A handful of these articles have specifically
addressed the managerial implications of the SERVQUAL Gap 1 analysis: the
identification of employee and management perceptions of consumer expectations
(Mangold and Babakus, 1991; Headley and Choi, 1992; Bebko, 1994). Previously,
none of the research had mentioned the potential problems inherent in Gap 1
analysis when the organization is faced with several "types" of customers, each
with possibly different expectations. Consequently, the results of the GAP 1
analysis may not represent the true picture of employee perceptions of consumer
expectations. This would have implications for the validity of the SERVQUAL
instrument in assessing a service's ability to deliver quality to consumers.
PMID- 10186253
TI - The number of times attended as a factor in the success of a comprehensive
hospital-based approach to health promotion.
AB - This study assesses the relationship between a perceived change in a health
related behavior or attitude and the number of times an individual participates
in a weekly hospital-based health promotion program. A survey was distributed to
participants in April 1995. A univariate probit evaluation shows that the number
of times attended and age have positive effects on the likelihood of change. As
the number of times an individual attends increases, the more likely the person
is to change, possibly revealing a reinforcement mechanism. It is important to
learn the most effective way to raise attendance so the reinforcement process
reaches more individuals.
PMID- 10186254
TI - Referring physician satisfaction: toward a better understanding of hospital
referrals.
AB - Customer satisfaction literature has contributed significantly to the development
of marketing strategies in the health-care arena. The research has led to the
development of hospital-driven relationship marketing programs. This study
examines the inclusion of referring physicians as partners in the hospital's
relationship marketing program. In exploring this relationship, medical and
hospital facility characteristics that referring physicians find important in
making patient referrals to specialty care hospitals are identified and analyzed.
The results lead to the development of strategic initiatives which hospital
marketers should consider when developing relationship marketing programs
designed to satisfy their referring physicians.
PMID- 10186255
TI - Developmental stages and spiritual coping responses among economically
impoverished women living with HIV disease.
AB - Identifies environmental markers, situational appraisals, perceived ability to
mediate situations and outcomes, primary coping strategies, and purposes served
by religion and spirituality in 10 HIV-positive women recruited from a regional
health care clinic. Findings indicated that the women experienced a
disintegration of family during their early developmental years, yielding
feelings of hopelessness and isolation; that their sexual development was marked
by rape and incest, and their early adulthood was characterized by failed
relationships, pregnancies, drugs, and alcohol. Reports that the women's
religious influences were predominantly maternal and provided a model for
intercessory prayer. Notes that prior to their diagnosis of HIV, participants
described their coping as escapist, while after diagnosis they believed there was
a divine intercession renewing their spiritual growth and connectedness with
others. Reports that the women's personal spirituality was greatly influenced by
prayer, television ministries, and reading the Bible. Suggests the interventions
that actively recruit women into social support services, health care systems,
and faith congregations are needed and that television ministries may serve as
access points for connecting women with necessary services.
PMID- 10186256
TI - Toward a postmodern chaplaincy.
AB - Explores metaphorical models for chaplaincy which yokes scientific and
theological projects in an effort to stimulate dialogue regarding ways the
healing arts of spirituality and the roles of chaplains may be crafted. Uses
clinical case materials and theological and scientific perspectives to illustrate
a vision for a postmodern chaplaincy.
PMID- 10186257
TI - The clergy and art therapy.
AB - Defines the professional minister as subject to confining social attitudes and
expectations. Posits clergy as good candidates for art therapy. Reports on a
small pilot study that field tested a curriculum exploring the relationship
between preaching and mental health and made use of several art activities. Uses
results of this study to illustrate art therapy's potential to free clergy for
authentic expression and to explore the potential and the problems posed by
clergy as a target group for additional research.
PMID- 10186258
TI - A personal reflection. The prayer box.
PMID- 10186259
TI - A personal reflection. "Soul therapy".
PMID- 10186260
TI - A personal reflection. Mothers in crisis.
PMID- 10186261
TI - A personal reflection. "I've never done this before".
PMID- 10186262
TI - He heals on wheels.
PMID- 10186263
TI - Here's looking at: malpractice. How did it ever come to this?
PMID- 10186264
TI - Tales from the dark side of medicine.
PMID- 10186265
TI - Always an open door, always enough time.
PMID- 10186266
TI - Here's looking at: medical education. Labs, lectures, and sleepless nights.
PMID- 10186267
TI - Time to hang up the white coat?
PMID- 10186268
TI - This proud profession must heal itself.
PMID- 10186269
TI - Physician, and friend, to a city's homeless youth.
PMID- 10186270
TI - Here's looking at: medical politics. Carrying the caduceus into battle after
battle.
PMID- 10186271
TI - Twice a survivor, he knows what comfort is.
PMID- 10186272
TI - Reflections on the stuff of a doctor's life: from the '20s to the '50s.
PMID- 10186274
TI - Traveling Dad's path, making my own footprints.
PMID- 10186273
TI - Saving lives on a global scale.
PMID- 10186275
TI - Affirming life in the face of death.
PMID- 10186276
TI - As you see it--our special survey. You're hassled. Here's why.
PMID- 10186277
TI - To him, patients are part of the family.
PMID- 10186278
TI - As you see it--our special survey. Your smartest moves, your worst mistakes.
PMID- 10186279
TI - As you see it--our special survey. Your strongest allies, your toughest enemies.
PMID- 10186280
TI - "It's easier to give charity than to ask for it".
PMID- 10186281
TI - As you see it--our special survey. You're coping, but you still can dream.
PMID- 10186282
TI - Senior doctors, senior care: an idea that works.
PMID- 10186283
TI - Reflections on the stuff of a doctor's life: from the '60s to today.
PMID- 10186284
TI - He goes home again--to give something back.
PMID- 10186285
TI - "Dagnabit, I've made progress!".
PMID- 10186286
TI - Here's looking at: doctor payment. Take the money and grumble.
PMID- 10186287
TI - For a new doctor, the old dream lives on.
PMID- 10186288
TI - She heeded a call, and transformed a town.
PMID- 10186289
TI - Here's looking at: doctor-patient relations. Good news--the pedestal is gone.
PMID- 10186290
TI - Speaking out for the kids who can't.
PMID- 10186291
TI - Here's looking at: communication. Staying connected: from the party line to the
Internet.
PMID- 10186292
TI - A whole day off? For him, never.
PMID- 10186293
TI - Here's looking at: medical technology. The uneasy balance of doctors and their
machines.
PMID- 10186294
TI - Medicare+Choice: big fanfare, but where's the party?
PMID- 10186295
TI - Malpractice hot spot: the "City of Brotherly Love".
PMID- 10186296
TI - Financial records: which to keep, which to toss.
PMID- 10186297
TI - Point, click--presto, you're an MBA!
PMID- 10186298
TI - Big pluses--and minuses--of electronic prescribing.
PMID- 10186299
TI - Referral denied ... and it cost this HMO $1 million.
PMID- 10186300
TI - The graceful goodbye: how groups phase out their older doctors.
PMID- 10186301
TI - Holding the line on overhead.
PMID- 10186302
TI - Managed care. Doctors: anti-managed-care sentiment runs deep.
PMID- 10186303
TI - Make physician-administrator teams work.
PMID- 10186304
TI - The seven deadly sins of physician practice management. How to stop committing
them to gain a competitive edge.
AB - Many words have been written about how the marketplace is changing--and hurting-
medical group practice. However, not all problems are external. Physicians and
managers are doing some of the harm to themselves. "Deadly sins," including a
lack of urgency, copycat strategies, trend chasing and the creation of
meaningless networks, inhibit growth. Avoiding these mistakes can make it easier
to handle those changes group practices can't control.
PMID- 10186305
TI - Strategic planning: today's hot buttons.
AB - The first generation of mergers and managed care hasn't slowed down group
practices' need for strategic planning. Even groups that already went through one
merger are asking about new mergers or ownership possibilities, the future of
managed care, performance standards and physician unhappiness. Strategic
planning, including consideration of bench-marking, production of ancillary
services and physician involvement, can help. Even if only a short, general look
at the future, strategic planning shows the proactive leadership needed in
today's environment.
PMID- 10186306
TI - Optimizing capacity: the key to managed care success.
AB - Success in managed care boils down to capacity: Having the right number of
physicians, doing the right things, at the right time, with the appropriate
support staff. Capacity analysis can give physicians an accurate comparative view
of their practice and help leaders make well-reasoned management decisions.
Examples are included.
PMID- 10186307
TI - Developing leadership: management skills for small group practices.
AB - The role of group administrators is changing as quickly as is the group practice
environment. The results of a survey of physicians and administrators in
physician-owned group practices with fewer than 15 physicians offers some
guidance. Physicians and administrators, the results show, have similar
expectations for administrators. They also agree that physician-administrator
teamwork has become more professional. The results also suggest that
administrators need the tools to be proactive planners for their organizations,
rather than passively responding to change.
PMID- 10186309
TI - Prepare well for joint venture assessment.
PMID- 10186308
TI - Difficult physician-patient relationships.
AB - Changes in the delivery of health care services in the United States are
proceeding so rapidly that many providers are asking how the working
relationships between doctors and patients will be effected. Accelerated by cost
containment, quality improvement and the growth of managed care, these changes
have caused some critics to feel that shorter visits and gatekeeper systems will
promote an adversarial relationship between physicians and patients. However,
proponents of the changing system feel that better prevention, follow-up care and
the attention to customer service these plans can offer will lead to increased
patient satisfaction and improved doctor-patient communication. Dedicated to
addressing these concerns, the Bayer Institute for Health Care Communication was
established in 1987 as a continuing medical education program (CME) focusing on
this topic. A half-day workshop on clinician-patient communication to enhance
health outcomes was introduced in 1992 and a second workshop, "Difficult'
Clinician-Patient Relationships," was developed two years later. The two courses
discussed in this article are offered to all physicians, residents, medical
students, mid-level providers and other interested staff within the Carle system.
PMID- 10186310
TI - A paler shade of gray. Or: returning the physician to the center of health care.
PMID- 10186311
TI - Negotiating or renegotiating managed care contracts.
AB - When negotiating or renegotiating a managed care contract, medical groups need
leverage. Medical groups have to offer the managed care company something it
can't get anywhere else in order to get the most advantageous contract. Leverage
can come by offering a large provider panel, geographic coverage or superior
quality, among other things. In every case, physicians benefit by being proactive
as they negotiate managed care contracts.
PMID- 10186312
TI - Medical groups and the metaphor of manufacturing.
AB - Medical groups are vitally interested in achieving better operating margins in
view of diminishing revenues and cost increases. The answer to this dilemma is
heightened productivity. However, raising the productivity of medical care
providers does not just automatically happen. It requires innovative thinking and
the courage to instill change in the face of resistance. This article examines
several medical manufacturing strategies that might be used by medical groups to
improve productivity. These strategies are based on proven approaches in business
that have been translated for the health care context.
PMID- 10186313
TI - Recent Medicaid payment developments.
PMID- 10186314
TI - Leading the way: 1998 leadership survey results.
PMID- 10186316
TI - Optimizing your instrument training experience.
PMID- 10186315
TI - New Federal guidelines for hepatitis C virus lookback.
AB - Given the recent approval of treatments for the hepatitis C virus, the FDA has
issued guidelines on testing, tracing, and notification procedures regarding
blood donor testing for hepatitis C. The deadline to begin this lookback policy
is September 20, 1998, so understanding these regulations, as well as the legal
and ethical risks of noncompliance, is imperative.
PMID- 10186317
TI - Point-of-care testing versus central lab costs.
PMID- 10186319
TI - Pulling out all the stops. Cardinal-Allegiance deal reshapes supply-side
landscape.
PMID- 10186318
TI - Risks and recommendations for HIV occupational exposures.
AB - The Public Health Service recently updated its recommendations for
chemoprophylaxis after exposure to HIV. These recommendations correlate the use
of antiretroviral agents with the risk of infection, which is determined by
evaluating the exposure and the potential for transmission from the source
patient.
PMID- 10186320
TI - N.M. tribe plans Medicaid HMO.
PMID- 10186321
TI - Exit with caution. Fla. investigates HMOs leaving Medicare markets.
PMID- 10186322
TI - Satellite heads for Wyoming. Foreign med school plans to expand despite protests.
PMID- 10186323
TI - Don't let CHIP fall where it may. Hospitals, health systems should pitch in to
extend coverage to uninsured kids.
PMID- 10186325
TI - Income outcomes. MGMA: doctors fare better in hospital-owned practices.
PMID- 10186324
TI - Evolution or extinction? Experts say HMOs must reinvent themselves if they are to
survive.
AB - Will HMOs in their current form survive into the next millennium? Some experts
say the dominant model of managed-care plans has already outlived its usefulness
and without major changes will face extinction. One consultant says the managed
care industry hasn't invested enough money in critical information technology and
has been "largely anti-consumer in terms of practices and policies."
PMID- 10186326
TI - Self-rating in Mass. Hospitals, seeking quality and accountability, to
disseminate patient-care data.
PMID- 10186327
TI - Loading up on debt. Bond issuances on track to break $29 billion record.
PMID- 10186328
TI - First around begins. Committee will choose sites for Medicare demo project.
PMID- 10186329
TI - Emerging power? McKesson, HBO & Co. marriage raises some eyebrows.
PMID- 10186330
TI - Heavily larded. Federal spending bill fat with healthcare measures.
PMID- 10186331
TI - Alluring offers. DMC claims rival used excessive pay to steal docs.
PMID- 10186332
TI - Fla. HMO on the brink. Needs cash infusion to meet state solvency rules.
PMID- 10186333
TI - Columbia probe has deep roots.
PMID- 10186334
TI - Minority enrollment rises. Calif. med schools see slight increase for 1998-99.
PMID- 10186335
TI - AHA may disband its house. Board of trustees would govern association.
PMID- 10186336
TI - Defending managed care. Coalition works to reverse health plans' negative image.
PMID- 10186337
TI - Healthcare issues on the ballot. Initiatives deal with medical marijuana, doc
assisted suicide.
PMID- 10186338
TI - Staging a comeback. Lawmakers push votes to lay groundwork for next year.
PMID- 10186339
TI - Keep ERISA intact. Instead of trying to dismantle the laws, Congress should
extend its incentives.
PMID- 10186340
TI - Wrestling with risk. Risk-management award winners find that a little effort can
lead to big rewards.
AB - It can cut costs, improve care and even create a bond between caregivers and
patients. In other words, a little risk management can go a long way. That's the
experience of the winners in the annual risk-management awards. This year's
winners are the University of Pennsylvania Health System, Philadelphia, and
Phoenix-based Arizona Physicians IPA. Two other organizations won honorable
mentions.
PMID- 10186341
TI - Complementary care. Partnership pairs primary care with alternative therapies.
PMID- 10186342
TI - Treating the student body. Company specializes in managing college health
services.
PMID- 10186343
TI - Desperate measures. Home health agencies do what it takes to stay afloat.
PMID- 10186344
TI - Role of GPOs debated. Are buying groups or systems best way to control costs?
PMID- 10186345
TI - Operating in reverse. Audit firms seek treasure buried in old invoices.
PMID- 10186346
TI - Fraud-fighting machine. N.Y. Attorney General takes on managed-care abuse.
PMID- 10186347
TI - Parental help. Kentucky HMO gets another big loan to stay on its feet.
PMID- 10186348
TI - AHA buys ads for candidates.
PMID- 10186349
TI - Dental group drills FTC. High-court case questions authority over not-for
profits.
PMID- 10186350
TI - The silent treatment. Senior, physician groups are mum about departures from
Medicare+Choice.
PMID- 10186351
TI - A world of difference. Access to care dependent on payment systems, wealth,
cultural traditions.
PMID- 10186352
TI - Healthcare international.
AB - How people are treated when they need medical care depends on where in the world
they are. In deciding which tools of the medical trade are used to treat disease
and when they're used, location is paramount. A country's social policy,
healthcare payment systems and cultural factors bear heavily on the utilization
of medical technology. The cover story kicks off the magazine's third
international healthcare section.
PMID- 10186353
TI - Medica unites world of healthcare.
PMID- 10186355
TI - No global Kaiser. International unit seen as a consulting arm for now.
PMID- 10186354
TI - Kaiser loses $102 million in third quarter.
PMID- 10186356
TI - The doctors are in. International Blues plan will let enrollees see physicians
nearly anywhere.
PMID- 10186357
TI - How was the care, chap? Picker hired to survey Brits on National Health Service.
PMID- 10186358
TI - Benchmarking East Asia. Arthur Andersen study aimed at upgrading healthcare in
developing nations.
PMID- 10186359
TI - Taking pains. Companies offer differing healthcare for overseas workers.
PMID- 10186361
TI - Managed care poised to take Europe.
PMID- 10186360
TI - From access to X-rays. Professor building database of world's healthcare finance.
PMID- 10186362
TI - JCAHO worldwide. Accreditation agency extends an international arm.
PMID- 10186363
TI - Taking a global risk. MMI Cos. sees gold in foreign malpractice insurance.
PMID- 10186364
TI - The price of technology.
PMID- 10186365
TI - Destination unknown. Mexico faces healthcare technology crossroads.
PMID- 10186366
TI - 'Perfect surgical day' aims for quick improvements.
PMID- 10186367
TI - Outpatient PPS proposal is met with apprehension.
PMID- 10186368
TI - Delay in ASC (ambulatory surgical centers) pay plan is relief to centers.
PMID- 10186369
TI - Avoiding pitfalls of clinical pathways.
PMID- 10186370
TI - Consulting shifts buyer-seller roles.
PMID- 10186371
TI - Managing today's OR suite. Creating meaning in the workplace.
PMID- 10186373
TI - Alliances benchmarking anesthesia-related costs.
PMID- 10186372
TI - Regional, local blocks speed recovery.
PMID- 10186374
TI - Guidelines issued for infection control.
PMID- 10186375
TI - Robots help with high-tech surgery.
PMID- 10186376
TI - New robots are arriving in the OR.
PMID- 10186377
TI - California law mandates safer needles.
PMID- 10186378
TI - The Pinata syndrome.
AB - The Pinata Syndrome is manifested by physician lounge grumbling and griping;
sniping at medical and administrative leadership; resistance to examining best
practices; refusal to hold colleagues responsible for their behavior, and general
melancholy. This disease is characterized by grousing physicians who do not enjoy
the practice of medicine and if self treated will leave medicine. It is
accompanied by patients who receive inappropriate care and caring. The treatment,
which can result in an excellent prognosis, is self-administered and must be
vigorously pursued to avoid chronic Pinata Syndrome, a professional death.
PMID- 10186379
TI - I can't believe they think I'd....
AB - Many physician executives experience a personal jolt as they move to work in a
very different relationship with their colleagues. What happens? How can we
understand this phenomenon? What can we do to minimize the personal toll so often
exacted by the transition to leadership? This paper will focus on these essential
questions. The inevitable discomfort encountered during this learning curve,
which can last from two months to two years, often comes as a surprise. Many
physicians who have been elevated to leadership positions because of their
success and interpersonal acceptance, have not had to struggle with this sense of
being "a fish out of water" since very early in their professional careers.
Unless there is someone in place to reassure and mentor, the resulting confusion
can be quite unnerving, resulting in reflex defensiveness.
PMID- 10186380
TI - A chilly reception: from the operating room to the board room.
PMID- 10186381
TI - Physician resiliency?
AB - The profound changes in the health care industry have led to the anger,
frustration, and unhappiness that physicians are feeling. It is important to
examine physicians' responses to the threats to their professional autonomy,
image, lifestyles, and relationships with their patients. The "learned
helplessness" behavior exhibited by physicians is astounding, considering the
education, status, and reputation of physicians as healers for those in need.
This article explores the concept of resiliency among physicians and describes
why physicians as a group may be less resilient than other individuals. In fact,
the structure and training of the medical profession stacks the deck against
those who want to change or to be resilient in the face of the changing
environment.
PMID- 10186382
TI - The physician leader as logotherapist.
AB - Today's physicians feel helpless and angry about changing conditions in the
medical landscape. This is due, in large part, to our postmodernist world view
and the influence of corporations on medical practice. The life and work of
existentialist psychiatrist Viktor Frankl is proposed as a role model for
physicians to take back control of their profession. Physician leaders are in the
best position to bring the teachings and insight of Frankl's logotherapy to rank
and-file physicians in all practice settings, as well as into the board rooms of
large medical corporations. This article considers the spiritual and moral
troubles of American medicine, Frankl's answer to that affliction, and the
implications of logotherapy for physician organizations and leadership. Physician
executives are challenged to take up this task.
PMID- 10186383
TI - After the revolution: the physician executive of the future.
AB - There is a revolution in health care occurring in our midst. The roots of this
revolution are explored. The physician executive of the future will need a new
set of skills because the health care system will change. This new, evolving set
of skills includes being: Savvy about business; simultaneously employer- and
customer-focused; and technologically driven. This manager must be a team builder
rather than a lone ranger. These skills are learnable, just like piloting a plane
or doing a surgery. None of us was born with the skill to practice medicine any
more than we were born with business skills. While many physicians are depressed
by the present health care climate, feeling a loss of power and a loss in spirit,
the vision of the physician manager must carry them and the organizations they
build forward through uncharted waters to a future which is every bit as exciting
as our past.
PMID- 10186384
TI - Serf or citizen: physician status and organizational structure.
AB - For more than a decade, dynamic changes in the health care industry have created
new organizations for physicians. The major change for physicians has not been
the organization itself, but the principles by which it is governed. This
fundamental shift is studied with its impact on physicians, by analogy, becoming
more like serfs or more like citizens. A review of the general organizational
direction and results of non-physician health care organizations is made followed
by the statistical trends of physician groups. Historical comparisons of non
health care industries are made with current organizational choices of physicians
and physician groups. Observations of physician decisions are made identifying
the direction they send physician status along the continuum from serf to
citizen. Physicians are unknowingly making decisions regarding the principles by
which they will be governed in new organizations. The choices they are making
give them less autonomy and less opportunity to make future choices. The
seductive invitation to spend less time in administrative matters and more time
practicing medicine is a siren's call that will diminish the status of physicians
and the autonomy by which medicine is practiced.
PMID- 10186385
TI - Sustainability as the lynch pin of public policy and industry initiatives.
AB - Does managed care have a sustainable future? So far, managed care has not lived
up to its promises and potential. Admittedly, the health care system prior to
managed care was a non-system. But its features included committed health care
professionals, caring local institutions, freedom of choice, and laws reflecting
public confidence. And it was based on the assumption that needed health care
services are a customary, moral, and implied legal right of U.S. citizens. In
contrast, today's version of managed care is characterized by financial and legal
manipulation, "choice" constricted by provider selection of physician panels, and
laws reflecting lack of public trust. Managed care can survive its initial
foolish years, if it heeds the voices of those urging that two priorities be
reflected in public policy, legislative efforts, and business practices. One of
these priorities is accountability for today's actions. The other is preserving
this country's health care resources. This article explored the concept of
sustainability--the need to strike a balance between seeking immediate profit and
preserving available resources.
PMID- 10186386
TI - Is it change? Or is it noise?
AB - How can you tell the difference between mere noise, and a profound change headed
your way? Your gut instincts may not always be a reliable gauge. It takes a long
time for most people to become an executive leader. If you are typical, you were
raised and trained in a different era, with different expectations. You see
things with different lenses. So what can you trust? You can trust first
principles. Ask yourself what you know about the reasons that changes are
happening in this environment. Then ask yourself about what is being proposed-
how does it fit with the roots of the changes in health care and your
organization? The three change filters presented here can help you to figure out
if it's change or just noise. Ask yourself: (1) what are the changes occurring in
the health care industry; (2) is your organization ready for change; and (3) how
likely is it that your organization will easily adopt this particular change?
These three filters together will help you decide what is a truly important
change, how ready your organization is for change, and whether it will adapt to
this change with ease or difficulty.
PMID- 10186387
TI - The future of health care, Part 2. The PPMC debate. Panel discussion.
AB - In Part 2 of this second annual panel discussion, Jeff Goldsmith, Barbara
LeTourneau, Uwe Reinhardt, and physician executives from three physician practice
management companies (PPMCs) examine this burgeoning new industry. They grapple
with questions (and occasionally with each other), such as: Are PPMCs delivering
what they promise? What will separate successful PPMCs from the rest? When PPMCs
win, who loses? What value do PPMCs add to health care? What lies ahead for this
industry? Could Wall Street pressure cause PPMCs to put profit ahead of
physicians and patients? And, what roles will physician executives play in PPMCs?
PMID- 10186388
TI - A crash course in conflict resolution.
AB - Knowing how to resolve conflict with finality establishes positive changes in
coworker relations, prevents drops in productivity, and frees a manager's time
for more important issues. Conflict arises from four sources: (1) Real or
imagined differences in values, (2) dissimilar goals, (3) poor communication, and
(4) personalizing generic or organizational issues. Right now health care is full
of the latter. It's possible--and useful--to make conflict productive rather than
disruptive. The secret is using a process that produces a solution acceptable to
everyone. This requires three steps: (1) Value differences must be addressed, (2)
communication styles must be established, and (3) everyone must commit to
mutually satisfactory resolution of the issues.
PMID- 10186389
TI - Skills needed by physician CEOs. Interview by Barbara J. Linney.
AB - How do you transition from physician executive to physician CEO? Three physician
CEOs were interviewed to explore the skills they needed to land in the top
position. They share their views on what it takes to be a successful CEO. They
describe the skills that they needed when they moved into the CEO role and how
they acquired them. Some of the qualities it takes to be a CEO include the
ability to: Articulate your values; use your people skills; describe a vision;
solve problems; listen; walk around; and use analytical skills.
PMID- 10186390
TI - The Zen of physician initiatives.
AB - Many physicians today feel ravaged by the brutal speed with which change has been
occurring. They see the beliefs and practices of a lifetime being abandoned and
replaced by the flavor of the month, management du jour. But if you are willing
and able to take the brave step of approaching your physicians without an agenda,
meeting with them to listen to their concerns, and can also avoid hanging a
lightning-rod label on every bright new idea that comes out of the sessions,
you'll be on the way to effective new management. This new style is a "Zen"
approach (but don't give it that label) that lets real collaboration come into
the place that is supposed to be all about healing--the health care organization.
From "never call it anything" to "stay with them until they get it," ideas on how
to be a Zen manager are presented, with the ultimate goal of truly partnering
with physicians and infusing them with a desire to move beyond the frustration
and disenchantment they are feeling.
PMID- 10186391
TI - Medicare private contracting: increasing patient choice and access?
AB - Congress modified the Medicare program through the Balanced Budget Act of 1997 to
expand patient choices for payment to physicians and certain other practitioners
by allowing private contracting. This represents a shift in policy that has broad
consequences for health care financing and program integrity. The effect of
private contracting on quality and access to care remains unknown. Quality and
access should be the most important measures of its success or failure. Out of
pocket costs to seniors and vulnerable patients must also be watched closely.
PMID- 10186392
TI - N.Y. ad shop creates campaign to destigmatize mental illness.
AB - Seventy-year-old Hillside Hospital, Glen Oaks, N.Y., decided the time had come to
build awareness of mental illness over time, both to destigmatize the disease and
to encourage those suffering from it to seek help, as well as reinforcing the
capabilities and importance of the facility to encourage people to choose
Hillside, a 223-bed psychiatric hospital, as their treatment center. Hillside
tapped The Benjamin Group, a fast-growing, full-service New York advertising
agency that specializes in creative new approaches for the health care industry,
to develop a long-term campaign for the psychiatric hospital. The primary
objective is to build awareness of mental illness, Hillside Hospital and the
treatments available, and to encourage those suffering from mental illness to
seek help. Secondarily, since Hillside Hospital has been involved in a capital
expansion project, the agency sought to increase awareness among the community in
general, trustees and other influential people in order to prompt donations to
Hillside's foundation. Since the break of the original ad and the subsequent
campaign that launched in January, the number of psychological referrals has
remained in the top five of total referrals. The campaign seeks to educate and
promote the available mental health services in a positive light.
PMID- 10186393
TI - Vytra Healthcare forms a frequent user plan focusing on wellness.
AB - Vytra Healthcare's "Constellation Club" marks the first time the concept of
wellness has been applied to health plans. The Constellation Club is comparable
to a frequent flier club in the airline industry.
PMID- 10186394
TI - "Values-based medicine" ads capture attention for New England health care
network.
AB - When nearly 70% of Boston area fishermen said they couldn't afford quality health
care for their families, Caritas Christi Health Care System teamed with
Massachusetts Fisherman's Partnership to offer low-cost health coverage.
PMID- 10186395
TI - Singing the national anthem at major league baseball stadiums raises awareness of
ALS.
AB - Mark Reiman, diagnosed with Amyotrophic Lateral Sclerosis (ALS), is raising
awareness of the disease, better known as Lou Gehrig's disease, by singing the
national anthem at all the major league baseball stadiums in the U.S.
PMID- 10186396
TI - Promoting HIV testing proves to be a challenging subject.
AB - BGM, a Los Angeles-based advertising agency, has created a campaign for the
Pediatrics AIDS Foundation to promote awareness of the importance of HIV testing
of all pregnant women. The agency is taking a personal stake in the campaign by
offering its services pro bono.
PMID- 10186397
TI - Healthy Heart endeavors appeal to the surrounding Sheffield, Ala., area.
PMID- 10186398
TI - New marketing alliances can help health care groups stand tall in a changing
market place.
PMID- 10186399
TI - Physicians find a "virtual club" through a Web site called POL (Physicians'
Online).
PMID- 10186400
TI - Varian Associates Inc. provides an alternative treatment for cancer.
PMID- 10186401
TI - Rockford Health System broadcasts the life-saving technology of "delayed interval
delivery".
AB - The public relations staff created campaign strategies that would draw attention
to Rockford Health System and its ability to provide highly technical care to
pregnant women and their babies.
PMID- 10186402
TI - Kaiser captures spirit of games.
AB - With a multi-media campaign, Kaiser Permanente blitzed its market area by
becoming a sponsor of the Nike World Masters Games. The advertising campaign
promoted Kaiser as the exclusive health care sponsor. Company officials are
counting on this campaign to leverage the health care institution's commitment to
the community. In addition to the advertising, Kaiser searched for local athletes
to represent its "play the sports for life" theme. As part of a promotion to
award 200 athlete sponsorships to the Games, Kaiser's own master athletes were
invited to tell their stories. Some of the members shared stories about such
topics as experiencing an accident, receiving assistance from a Kaiser physician
and incorporating a lifestyle of sport for rehabilitation. From the hundreds of
letters received, two members and one employee were selected for the television
spots. The sporting event reinforces Kaiser's philosophy of fitness-oriented
lifestyles among its members. The Nike World Masters Games are the largest
participatory multi-sport competition in the world, gathering together more than
25,000 men and women from more than 100 countries.
PMID- 10186403
TI - Surgical suite in cornfield helps rural hospital retain care in hometown.
AB - Administrators of Hannibal Regional Hospital in Hannibal, Mo., wanted to identify
the facility as an advanced rural medical center that would be attractive to
those who felt they needed to leave the area for medical care, when in fact the
services they sought were available locally.
PMID- 10186404
TI - "First steps" campaign a hot item for Akron's Summa Health System.
AB - When Summa Health System in Akron, Ohio, decided to market its high level of
maternity services it teamed up with an Akron ad shop and together they produced
a 15-minute home video that features couples telling about their positive
experiences. The free video was so popular that 1,300 copies were distributed in
the first month they were available.
PMID- 10186405
TI - "Let's take it outside" campaign raises awareness, changes attitudes. Kansas
Health Foundation.
AB - Kansas Health Foundation overcomes smokers' built-in defenses by applauding those
who protect others from their smoke. Rather than depend on public service
announcements to get the word out on the dangers of second-hand smoke, the
Foundation insisted on paid commercials, pumping $4 million into the statewide
campaign.
PMID- 10186406
TI - Provocative billboard promotes legislation for hepatitis C education, screening.
American Liver Foundation, San Diego Chapter.
AB - California proponents of legislation that would provide education, screening and
treatment for the silent killer Hepatitis C used a provocative billboard on the
route between Sacramento's airport and capital to catch legislators' attention.
The startling billboard caught much more than the attention of passersby.
PMID- 10186407
TI - Bridge Medical creates an emotional campaign with true tales.
AB - Bridge Medical tells a compelling story about America's "other drug problem" by
getting its point across through heart-wrenching, emotional testimonies of
patients, families, physicians, nurses and pharmacists. The overall strategy was
to present the "issue," not the product, in a dramatic and truthful manner,
building upon the highly emotional and controversial nature of the problem.
PMID- 10186408
TI - "Gutsy" print ad raises consumer awareness about hernia repair.
AB - A Newton, Mass., ad shop creates a first-ever, direct-to-consumer advertising
effort to-raise awareness among both primary care physicians and consumers
regarding hernia repair coinciding with National Hernia Month.
PMID- 10186409
TI - The Centers for Disease Control partners with Lysol manufacturer.
AB - The Centers for Disease Control and the makers of Lysol join a partnership to
create a program for prevention methods called "An Ounce of Prevention Keeps the
Germs Away." This program teaches the general public, especially families with
young children ages 2 to 12, seven simple and inexpensive ways to prevent the
spread of infectious disease.
PMID- 10186410
TI - Tragedy prompts depression awareness, suicide prevention campaigns.
AB - The tragic suicide of Robert C. Goltz prompted associates at the integrated
marketing and communications company he founded in Green Bay, Wis., to develop
two multimedia campaigns, one focusing on depression awareness and the other on
suicide prevention.
PMID- 10186411
TI - Radiology support services: a solid foundation.
PMID- 10186412
TI - What used to be easy is hard.
PMID- 10186413
TI - The regulation of silver recovery.
PMID- 10186414
TI - Five PACS administrators speak out. Interview by Nancy Fowler.
PMID- 10186415
TI - On the road to PACS--confronting the issues.
AB - In 1992, PACS became a serious consideration for me, the new administrative
director of medical imaging, and a team approach seemed the sensible means to a
topic so large. Even with our limited knowledge of PACS at that time, the team
knew it would take years to deploy a PACS system fully. Members realized it would
be one thing to design a complete PACS and quite another to break the whole into
functional, logical and compatible parts. Yet how could we plan for something so
sophisticated when we couldn't even agree where to begin? The team, recognizing
the financial challenges of calculating cost/benefits, finally determined that
the cost of PACS would exceed obvious savings. Ultimately, we determined that
PACS efficiencies would enable us to go after new business. But were there hidden
costs? How could we balance costs with benefits that are seemingly valid but hard
to quantify? To answer such questions, the team broke the process into steps and
planned each part of every step. Implications for PACS outside the radiology
department became an issue. How would the PACS, RIS and transcription systems
work together to handle images and reports? What about referring physicians? Will
patient care improve? After inviting major image-printing vendors to make
presentations for a print network, the team selected a firm endorsed by our
information technology services department. Where once there was confusion, the
team accomplished its goals of reducing costs, improving efficiency, and
maintaining high standards for patient care.
PMID- 10186416
TI - Making PACS the present, not the future.
AB - Why haven't you moved forward with PACS? Have you just procrastinated or does
your facility have legitimate reasons? Some say the technology is too confusing
or too new, while others say the cost of PACS is too high. Many facilities say
they haven't found a satisfactory way to deal with the conflicting opinions of
their radiologists, IS department, administration, referring physicians and
staff. Take time to compare the technology you do understand with something
familiar such as your own PC or perhaps the current networks inside your
facility. You'll soon begin to see that PACS is not a new technology, but rather
a new methodology. To handle the perceived high cost of PACS, remember that every
facility has different needs. Look at your work flow and then the many byproducts
of PACS, such as marketing. If you are the first in your area to implement this
new technology, you'll gain a marketing advantage in competing for referring
physicians and managed care referral business. Follow the process you use to
purchase other products, such as CT or MRI, as you investigate the vendors.
Finally, make a plan! Determine departmental goals and gather information from
vendors. Create a timeline, a financial plan and your marketing strategy.
Together, these steps will help move PACS into the present for you.
PMID- 10186417
TI - All you need to know about a PACS RFP, you learned in kindergarten.
AB - Key to purchasing any picture archiving and communications system (PACS) is the
generation of a request for proposal (RFP), which defines the system's
requirements. An RFP is not difficult to create and, in fact, one can follow
simple rules such as outlined in Robert Fulghum's book, All I Really Need to
Know, I Learned in Kindergarten. "Take time to look" is the first rule--don't
jump into new adventures. Instead, start with a mission statement and clear
objectives. Define the stakeholders and assemble the team. "Share everything" is
the second rule to follow. This includes information, objectives and definitions
of the problem. You'll want to define your specifications. What are the component
requirements? How will you integrate information systems at your facility? What
about performance--how is it defined and what is expected? Warm cookies and cold
milk--or common sense--is another rule, particularly around issues that may seem
obvious such as training and service. Who is going to do it, and what is
required? "Watch out for traffic and hold hands." This rule, as applied to PACS
and an RFP, means stick together. Create a partnership with your vendors. Talk to
as many vendors and other users as possible. Last, "be aware of wonder."
Fulghum's Rule, as applied here, means performance will speak for itself,
particularly when there is significant improvement in the service you provide to
your users.
PMID- 10186418
TI - Access control for electronic patient records.
AB - The transition from hardcopy records to electronic records is in the forefront
for healthcare today. For healthcare facilities, a major issue is determining who
can access patients' medical information and how access to this information can
be controlled. There are three components to access control: identification,
authentication and authorization. Checking proof of identity is a means of
authenticating someone--through a driver's license, passport or their
fingerprints. Similar processes are needed in a computer environment, through the
use of passwords, one-time passwords or smartcards, encryption and kerberos, and
call-back procedures. New in the area of access control are biometric devices,
which are hardware/software combinations that digitize a physical characteristic
and compare the sample with previously stored samples. Fingerprints, voiceprints
and facial features are examples. Their cost is currently prohibitive, but in
time, they may become more common. Digital certificates and certification
authorities are other means used to authenticate identify. When a system
challenges a user's identity at log on, the user provides a certification that
tells the system to go to the issuing certification authority and find proof the
user's claim is valid. Low-level certifications offer little value for sensitive
data, but high-level certification is now being introduced. It requires more
specific, detailed information on the applicant. Authorization, the final
component of access control, establishes what a specific user can and cannot
access. To have effective access control, transaction logging and system
monitoring are needed to ensure the various techniques are being used and
performing properly.
PMID- 10186419
TI - Film-free efficiency systems: a new cost-effective approach.
AB - Pressure is on healthcare providers to make their services more affordable.
Streamlining operations to improve efficiency is one means of achieving that
goal. PACS has been touted as the technology to improve radiologic services. Sold
as a way to eliminate lost records and lower operations costs, in reality, PACS
has raised costs and slowed work flow in many cases. Perhaps PACS that raise
operations costs are more properly named digital overhead generating systems
(DOGS). There is an alternative solution--film-free efficiency systems (FFES),
defined as the technological tools required to lower radiologic costs and improve
services. A new type of image and information management technology and distinct
from traditional PACS in a number of ways, film-free efficiency systems are
immediately cost effective. They improve personnel efficiency, reduce costs per
RVU, provide an alternative to film and exclude the use of any technology that is
not cost effective. Implementation of these systems must begin with a clearly
stated mission, a leadership statement and financial accountability. To guarantee
an immediate financial gain in your department, you'll want to finance the system
through material cost savings. Implementation should start with the digital
modalities. The next step is to retrain staff and reengineer the workplace,
followed by creating the necessary infrastructure of PCs in referring physicians'
offices. Lastly, implement CR or digital radiography as prices drop and
technologies improve in speed.
PMID- 10186420
TI - One face is worth a thousand words.
PMID- 10186421
TI - Redesigning governance for success.
PMID- 10186422
TI - Advise and consent. Trustees earn their stripes in political advocacy.
PMID- 10186423
TI - Considering conversion? Connect with your community first.
PMID- 10186424
TI - Through a trustee's eyes. Interview by Mary Grayson.
PMID- 10186425
TI - A bottom-line commitment to community benefit.
PMID- 10186426
TI - Patient satisfaction: what you see is what you get. You can't improve it unless
you know what patients think.
PMID- 10186427
TI - A healthy trend ends. New report predicts rising medical costs.
PMID- 10186428
TI - A shocking story: handy defibrillators. Devices kept at public venues could save
lives.
PMID- 10186429
TI - Trials of a cancer doc. Experimental drugs and a 20-year fight with the FDA.
PMID- 10186430
TI - There when you need it. U.S. News ranks 271 of the nation's HMOs and looks at an
innovator that stresses preventive medicine.
PMID- 10186431
TI - Plans that opted out. Many managed-care plans don't like how they're measured.
PMID- 10186433
TI - Outcomes and mortality ratios: different sides of the same coin?
PMID- 10186432
TI - How we ranked the plans. This year, 271 managed-care plans were analyzed 28 ways.
PMID- 10186434
TI - Obesity and life underwriting.
AB - Obesity is increasing in the US population and currently affects one-third of
adults. The physiology of obesity is complex and predisposition to obesity is
influenced by multiple genes and environment. Obesity may be measured by body fat
percentage, body mass index (BMI), or visceral adiposity. Life insurance
companies generally use height and weight (build) determinations. The purpose of
this paper is to review the life risks and physiology of obesity, and to suggest
that the current trend to liberalize traditional build table ratings may not be
prudent. A case history will be utilized to demonstrate these points.
PMID- 10186435
TI - Diabetes mellitus--long time survival.
AB - The medical literature of the last decade enables us to estimate survival of
diabetics. Insulin dependent diabetic (IDDM) present a 3 to 6-fold mortality and
die after age 30, the most frequent causes being end stage renal and vascular
diseases. Non insulin-dependent diabetic (NIDDM) mortality is 1.4 to 3.7 times
that of non-diabetics. Cardiovascular events and strokes are the major causes of
death. Pancreatic carcinoma occurs twice as frequently in NIDDM compared to non
diabetics. Early markers of late severe complications are hypertension and
proteinuria. Retinopathy has little influence on morality if other risk factors
are considered. Yet, glaucoma and lens changes are associated with three- and
twofold mortalities. One of five IDDM with microalbuminuria progresses to overt
nephropathy in 5 years. In NIDDM micro-albuminuria predicts cardiovascular
disease with a mortality of up to 2 times. Careful treatment of cardiovascular
risk factors and of microalbuminuria combined with optimal metabolic control
substantially reduces mortality of diabetics.
PMID- 10186436
TI - How to construct a Mortality Abstract (number 497M-1 as an example).
AB - BACKGROUND: Since the 1976 publication of the first Medical Risks volume of
analyses of mortality follow-up (FU) studies (called "mortality abstracts"),
members of the American Academy of Insurance Medicine have sought to extend this
method of using FU studies in the medical literature to produce comparative
mortality data useful for medical underwriting. Seminars on life table
methodology started in 1977 and courses are now sponsored by the Board of
insurance Medicine. The Journal of Insurance Medicine has published many
mortality abstracts and methodology articles, and methodology is further pursued
by the Editor in this issue of the Journal. TEXT: Retrieval of the source data
(Annual Reports) is described and the source tables are evaluated. These are
related to a previous 1976 Abstract. The design of the Abstract is described:
other sources, tables, background, expected mortality, descriptive text, and
comment. Aspects of life table methodology are used throughout the description.
SUMMARY: The construction of the current Mortality Abstract 497M-1 on mortality
in cystic fibrosis is described in detail.
PMID- 10186437
TI - A genetic testing code of practice for insurers.
AB - The Association of British Insurers has issued a Genetic Testing Code of
Practice. The document consists of a forward and six parts, namely; Code of
Practice, Statement of Duties of our Insurance Company's Chief Medical Director,
Statement of the ABI Genetics advisors responsibilities, Principals of the
adjudication system, the legal and ethical framework and confidentiality
guidelines.
PMID- 10186438
TI - Markedly elevated gamma-glutamyltransferase.
AB - Gamma-glutamyltransferase (GGT) is a highly sensitive but poorly specific liver
enzyme commonly used to detect hepatobiliary disease and possible alcohol abuse.
Isolated elevations of this enzyme may be due to biochemical anomalies rather
than the presence of pathology.
PMID- 10186439
TI - Limitations of using the apolipoprotein E genotype in the diagnosis of
Alzheimer's disease.
PMID- 10186440
TI - The effect of age on the association between body-mass index and mortality.
PMID- 10186441
TI - Underwriting lethal genetic diseases.
AB - There are thousands of single gene deposits that cause increased morbidity or
mortality risks. Few have complete penetrance leading to certain death. Most can
be underwritten with affordable increases in premium; many at standard rates. As
we learn more about penetrance for specific mutations we can learn to be more
aggressive in underwriting inherited risks. I have described approaches to
underwriting untested applicants to Huntington disease, and tested applicants who
carry dominant mutations leading to breast, ovarian and colon cancer.
PMID- 10186442
TI - The role of carotid arterial intima-media thickness in predicting clinical
coronary events.
PMID- 10186443
TI - Neurology.
PMID- 10186444
TI - Characteristics of acquired immunodeficiency syndrome in older adults.
PMID- 10186445
TI - A new pathologic classification of prostate carcinoma and the impact of margin
status.
PMID- 10186446
TI - The Association of British Insurers Genetic Testing Code of Practice.
PMID- 10186447
TI - Towards a psycho-social theoretical framework for sexual health promotion.
AB - Numerous interventions have been designed to promote safer sexual behaviour
amongst young people. However, relatively few have proved effective, which is, at
least partially, due to the lack of development of theoretically based
programmes. An understanding of the origins and control of sexual behaviour can
be derived from basic social science research. Unless this is applied to the
design of behaviour-change programmes they are unlikely to target the most
important determinants of young people's sexual behaviour and are, therefore,
unlikely to be effective. This paper outlines some of the key theoretical
insights which have been drawn upon in the development of a new sex education
programme currently being tested in Scottish schools. The theoretical basis is
intentionally eclectic, combining social psychological cognitive models with
sociological interpretations, since we are not concerned to advance any
particular theory but to find which are most useful in promoting sexual health.
First, the social influences on sexual behaviour are considered, and then the way
in which these translate into individual perceptions and beliefs. Finally, the
paper attempts to develop a theoretical understanding of sexual interaction and
the social contexts of sexual behaviour.
PMID- 10186448
TI - Relaying the message of safer sex: condom races for community-based skills
training.
AB - This paper describes a community-based HIV prevention program designed to improve
confidence in condom use skills by giving community members 'hands-on' experience
in using condoms correctly. A condom race activity which had been effective in
increasing condom skills confidence among university students in the US was
modified and implemented with the general population in rural Northeast Thailand.
In addition to providing training in condom use skills, the condom race was part
of an integrated condom promotion and distribution campaign which responded to
needs identified by the community, built upon the credibility and influence of
local leaders and peers, and extended access to condoms into rural communities.
Local leaders who had participated in a training-of-trainers program organized
condom races in their communities, serving as positive role models for community
acceptance of condom use. The condom race stimulated community discussion about
condoms and increased participants' feelings of self-efficacy in correct condom
use. Participation in the condom race activity was particularly empowering to
women, who reported increased confidence in their ability to use condoms and to
suggest using condoms with their partners after the race.
PMID- 10186449
TI - The promotion of healthy eating: food availability and choice in Scottish island
communities.
AB - Communities in rural areas are in receipt of health education messages on healthy
eating aimed at the population. These messages are invariably composed without
regard to where people reside, and, in particular, to the availability of, and
access to, foodstuffs in rural areas. In this paper the authors present data
derived from a participative health needs assessment on the topic of food, diet
and health. The research was conducted in a number of islands of the Western
Isles of Scotland and comprised seven focus groups, 33 semi-structured
interviews, one community and one policy workshop, and a final community feedback
session. The needs assessment demonstrated a dichotomy between local experiences
of food availability, island food cultures and the contents of healthy eating
advice. As a result of the research, local people and health care professionals
developed a range of activities on the topic of the traditional island diet.
People noted the potentially positive elements of this diet for health but also
the possibility of promoting social cohesion through the consideration of food
and diet histories. In addition, lobbying at a national level was also identified
as necessary to the development of a 'healthy food policy'.
PMID- 10186450
TI - Health salience: reclaiming a concept from the lost and found.
AB - This paper describes development of a new measure to assess one dimension of
health motivation, the salience of health concerns. The new, five-item, measure
was administered to 578 women as part of a larger investigation examining the
determinants of exercise and calcium consumption. The study used a cross
sectional survey research design. Data were analyzed separately for premenopausal
and menopausal women, allowing us to cross-validate our findings in two
independent samples. Our findings suggest that the new measure has many desirable
psychometric properties. It is internally consistent (Cronbach's alpha = 0.85 and
0.86 for premenopausal and menopausal women, respectively). For both samples,
factor analysis revealed that over 60% of the total item variance was explained
by a single underlying factor. All factor loadings exceeded 0.74. The measure
also correlated in predictable ways with measures of other health beliefs,
differentiated among women in different stages of change with respect to exercise
and calcium consumption, and discriminated between women on the basis of their
information-seeking behavior. We discuss the potential applications of this new
measure in future research. Hopefully, the measure will facilitate research on
the role that health salience plays in the behavior change process.
PMID- 10186451
TI - The interplay of socioeconomic status and ethnicity on Hispanic and white men's
cardiovascular disease risk and health communication patterns.
AB - In this article, we seek to confirm past studies that document increased levels
of cardiovascular disease (CVD) risk factors among White men with lower
educational attainment. Second, we include a population of Hispanic men (89%
Mexican American) to examine the separate and interactive effects of ethnicity
and education (our measure of socioeconomic status) on CVD risk factors. Third,
we examine how education and ethnicity are related to receiving health messages
from print media and interpersonal channels, with the hypothesis that less
educated, higher CVD risk Hispanic and White men receive fewer messages than more
educated men. Finally, we examine other psychosocial variables (e.g. knowledge,
self-efficacy and motivation) that may help explain observed differences in CVD
risk and health communication. The study sample included 2029 men, 25-64 years of
age, from three population-based, cross-sectional surveys conducted from 1979 to
1990 as part of the Stanford Five-City Project. Hispanic and White men with lower
educational attainment had higher levels of CVD risk factors, and received less
health information from print media and interpersonal channels than Hispanic and
White men with higher educational attainment. Furthermore, less educated men from
both ethnic groups reported less CVD knowledge, lower self-efficacy and lower
motivation to reduce CVD risk factors than higher educated men. These results
highlight the need for effective intervention programs that target low educated
Hispanic and White men to decrease their disproportionate risk of CVD.
PMID- 10186452
TI - A meta-evaluation of smoking cessation intervention research among pregnant
women: improving the science and art.
AB - In 1986 Windsor and Orleans described guidelines and standards to evaluate the
quality of smoking cessation intervention research among pregnant women. This
paper presents a meta-evaluation (ME) of the evaluation research in this area
from 1986 to 1998. ME is defined as a systematic review of experimental and quasi
experimental evaluation research using a standardized set of methodological
criteria to rate the internal validity--efficacy or effectiveness--of
intervention results. Five criteria were used to rate 23 smoking cessation
intervention studies among pregnant smokers in prenatal care: (1) evaluation
research design, (2) sample representativeness, sample size and power estimation,
(3) population characteristics, (4) measurement quality, and (5) replicability of
interventions. Eleven studies had sufficient methodological quality to produce
results of high internal validity. Poor measurement of smoking status, patient
selection biases and incorrect calculation of quit rates were the major
methodological weakness. Recommendations for future evaluation research are made.
PMID- 10186453
TI - Cost-of-illness studies. Useful for health policy?
AB - A sample of cost-of-illness (COI) studies was reviewed, which included studies
for specific diseases ('specific' studies) as well as those for the entire range
of diseases ('general' studies). Theoretically, COI studies may deliver suitable
information for health policy and rational healthcare spending. In practice,
however, the informative value of 'specific' prevalence-based COI studies is very
limited. A static picture of costs is presented in these studies, as trends in
costs are not being described or explained by factors such as demography,
epidemiology and technology. No practical link is offered between COI estimates
and economic evaluation. Incidence-based COI studies can provide more relevant
information for economic evaluation studies. It appears more useful to perform
general COI studies, as these provide comparable estimates of disease costs and
put cost estimates in a total healthcare perspective. Compared with specific COI
studies, general COI studies better facilitate the analysis and projection of
trends in costs, for example due to aging.
PMID- 10186454
TI - Update on clinical research summit in US.
PMID- 10186455
TI - The role of clinical pathways in reducing the economic burden of stroke.
AB - Clinical pathways are a potentially beneficial, but largely untested, management
strategy for both improving healthcare efficiency and decreasing costs while also
maintaining or improving quality of care. Although relatively few clinical
pathways for stroke have been described in the medical literature and although
the reported benefits have been mixed, more and more hospitals are adopting
clinical pathways as a management strategy for patients with stroke. In published
clinical pathways for acute stroke, the following benefits have been reported:
(i) reduced use of expensive diagnostic studies; (ii) fewer complications
(particularly the frequency of urinary tract infections and aspiration
pneumonia); (iii) reduced duration of hospital stay; (iv) reduced patient
charges; and (v) lower mortality. However, these reported benefits are not
consistent across all studies and some outcomes are highly correlated. Despite
potential benefits, many clinical pathway programmes fail because of inadequate
planning and shortcomings of implementation. Effective implementation of clinical
pathways requires strong administrative and medical staff leadership, active
participation of all clinical disciplines involved in the care of patients on the
pathway, provision of regular feedback to clinicians, sufficient resources,
improved documentation, incorporation of the entire episode of care into the
pathway, integration with ongoing quality and utilisation management programmes,
and periodic evaluation and modification.
PMID- 10186456
TI - Reporting format for economic evaluation. Part I: Application to the Dutch
healthcare system.
AB - This article presents the first version of the reporting format for economic
valuation that was created in 1995 by a multidisciplinary taskforce. The members
of this taskforce come from a broad spectrum of backgrounds within the healthcare
field and participated in the exercise voluntarily. The format presented should
be understood as the preferred Dutch structure for the reporting of any study on
economic evaluation. In view of the many areas of contention that exist within
the field, this format only gives normative directions in those areas in which
consensus exists, as evidenced by the current published international guidelines.
A regular review and adaptation of this format will be needed to reflect advances
in the field.
PMID- 10186457
TI - Cost effectiveness of prophylaxis for opportunistic infections in AIDS. An
overview and methodological discussion.
AB - Dramatic progress has recently been made in defining the pathogenesis and
treatment of HIV infection. For the first time in the history of the AIDS
epidemic, clinicians have at their disposal an understanding of the replication
kinetics of HIV, reliable assays to measure viral load, an increasing number of
effective agents to suppress viral replication and to reverse the process of
immune system destruction, and a range of options for the treatment and
prophylaxis of most of the major opportunistic infections in HIV disease. These
remarkable advances are not without their costs, however. New antiretroviral
therapies and opportunistic infection prophylaxis regimens impose considerable
financial strain on public and private budgets for HIV patient care. They force
decision-makers to confront a variety of competing considerations, including
issues of length and quality of life, the risks of adverse effects and
toxicities, and the dangers of promoting resistance. Questions regarding the
continued appropriateness and efficiency of opportunistic infection prevention
have prompted increased interest in studies of the cost effectiveness of HIV
patient care. In this article, we reviewed the literature on the economic
evaluation of prophylaxis for HIV-related complications. Section 1 provides
background on recent scientific and clinical advances. Section 2 reviews the
state-of-the-art understanding of the cost effectiveness of prophylaxis against
specific opportunistic infections. Section 3 broadens the discussion to consider
the more general question of optimal allocation of prophylaxis resources across
competing opportunistic infections. In Section 4, we briefly examined the
influence of cost-effectiveness evaluations on the development and refinement of
clinical guidelines for HIV-related opportunistic infection prevention in the US.
Section 5 presents some of the methodological challenges that arise in applying
the methods of cost-effectiveness analysis to the particular case of
opportunistic infection prevention in AIDS. We close, in Section 6, with a
comment on directions for further research.
PMID- 10186458
TI - A review of the pharmacoeconomics of pharmaceutical care.
AB - Numerous studies have demonstrated that the therapeutic use of drugs results in
adverse outcomes and contributes to high rates of morbidity and mortality. The
causes of drug-related problems are multifactorial and their assessment has been
based on factors such as inappropriate prescribing, inappropriate delivery,
inappropriate patient behaviour, patient idiosyncrasy and inappropriate
monitoring. The cost in the ambulatory setting has been estimated to exceed total
prescription pharmaceutical use. Pharmaceutical care is defined as the
responsible provision of drug therapy for the purpose of achieving definite
outcomes that improve a patient's quality of life. It describes the process
through which a pharmacist cooperates with a patient and other healthcare
professionals in designing, implementing and monitoring a therapeutic plan that
will produce specific therapeutic outcomes for the patient. This article
evaluates published studies related to the economic analysis of pharmaceutical
care in enhancing the value of pharmaceuticals. While numerous descriptive
articles exist, our review found no studies which met accepted pharmacoeconomic
criteria. A small number of studies measured process variables and/or quality of
life, but only one considered costs. Barriers to optimising the economic value of
pharmaceutical care were also explored. Common methodological shortcomings
indicated a need for improvement in future studies. There is little published
research to date which demonstrates the pharmacoeconomic benefits of
pharmaceutical care. Evidence does exist that clinical pharmacy services have
positive economic benefits, and it is this evidence that, at present, supports
the assertion that pharmaceutical care has potential to increase the value of
pharmaceuticals in society by minimising drug-related morbidity and mortality.
Thus, well conducted research is required to determine the economic impact of
pharmaceutical care.
PMID- 10186459
TI - Choice of NSAID and management strategy in rheumatoid arthritis and
osteoarthritis. The impact on costs and outcomes in the UK.
AB - OBJECTIVE: Although nonsteroidal anti-inflammatory drugs (NSAIDs) are an
effective therapy for rheumatoid arthritis, they are associated with significant
adverse effects, the management of which imposes additional costs on the
healthcare system. Prescribing NSAIDs which have a lower risk of major adverse
effects as the first-line NSAID for patients with rheumatoid arthritis and
osteoarthritis may be expected to lead to an improvement in clinical outcomes and
reduce overall treatment costs. This analysis examines data from a published
randomised controlled trial of 5 NSAIDs to explore these hypotheses. DESIGN AND
SETTING: Data from a clinical trial comparing 5 NSAIDs were combined with
published cost data to construct 2 clinical decision models, reflecting
alternative approaches to the management of major and minor adverse effects in
the UK. INTERVENTIONS: The 5 NSAIDs evaluated in the analysis were nabumetone,
diclofenac, ibuprofen, piroxicam and naproxen, although only the results for
ibuprofen and nabumetone are reported. MAIN OUTCOME MEASURES AND RESULTS: The
total cost of care per patient receiving nabumetone was estimated to be between
25 pounds sterling (Pound) and 41 Pounds more expensive than ibuprofen. In a
hypothetical cohort of 100,000 patients, there were between 690 and 821 more
major adverse effects using ibuprofen than nabumetone. The cost per life-year
gained (LYG) from using nabumetone rather than ibuprofen ranged between 1880
Pounds and 2517 Pounds (1995 values), depending upon the management of adverse
effects. CONCLUSIONS: These results indicate that: (i) prescribing the newer,
currently more expensive, NSAIDs will not necessarily lead to cost savings; (ii)
the management of adverse effects can have a significant impact on costs; and
(iii) the additional cost may be justifiable in terms of the mortality and
morbidity gains associated with the new lower-risk NSAIDs.
PMID- 10186460
TI - Quality of life following a change in therapy for diabetes mellitus.
AB - OBJECTIVE: The study objective was to evaluate and compare quality-of-life (QOL)
parameters between patients with type 2 (non-insulin-dependent) diabetes mellitus
who changed therapy from an oral hypoglycaemic agent (OHA) to insulin and those
who remained on an OHA. DESIGN: The World Health Organization Quality of Life
Questionnaire (WHOQOL) was used to assess quality of life among 2 groups of
patients with type 2 diabetes mellitus at baseline and after a 2-month follow-up
period. SETTING: The study was conducted in the outpatient department of the Vuk
Vrhovac Clinic, a referral centre for registration, treatment and follow-up of
patients with diabetes mellitus in Zagreb, Croatia. PARTICIPANTS AND
INTERVENTIONS: 32 consecutively recruited patients with type 2 diabetes mellitus
who were switched from an OHA to insulin therapy (group 1) were compared with 28
patients who remained on OHA (group 2) with respect to QOL issues. The patient
groups were comparable in terms of gender, age, duration of disease, education
and family status. However, patients in group 1 had glycosylated haemoglobin
(HbA1c) values greater than 9.5% on average during a period of approximately 6
months, which was the criterion used for switching to insulin therapy. MAIN
OUTCOME MEASURES AND RESULTS: At baseline, various QOL ratings were higher among
patients in group 2 than group 1, indicating better quality of life with respect
to overall quality of life (t = -2.31, p = 0.03), physical health (t = -2.36, p =
0.02), psychological state (t = -2.01, p = 0.05) and level of independence (t =
2.75, p = 0.001), while no differences were found between groups with respect to
the social domain, personal beliefs and environmental QOL aspects. After the
follow-up period, the groups were comparable in all QOL aspects other than
overall quality of life (t = -2.18, p = 0.03) and level of independence (t =
3.49, p = 0.001), both of which remained higher for patients in group 2. No
changes in QOL parameters were detected within group 2 from baseline to the end
of the 2-month follow-up period, whereas patients in group 1 showed significant
improvement in psychological QOL determinants (t = -2.14, p = 0.04). CONCLUSION:
Results of the study indicate that introducing insulin therapy in patients with
type 2 diabetes mellitus and sustained elevated HbA1c levels might positively
affect their quality of life.
PMID- 10186461
TI - Cost effectiveness of screening for subclinical hypothyroidism in the elderly. A
decision-analytical model.
AB - OBJECTIVE: The value of early detection of subclinical hypothyroidism is the
object of a long lasting debate. In this study, we assessed the cost
effectiveness of a policy based upon screening for this condition through thyroid
stimulating hormone (TSH), triiodothyronine (T3) and thyroxine (T4) serum level
measurements in the elderly. DESIGN: A Markov model was developed where
hypothetical elderly patients (i.e. > or = 60 years of age), who attend general
practitioner (GP) clinics for periodic health examinations in a primary-care
setting in Italy, made transitions between health states at annual interval for
15 years, thus allowing an estimation of the average cost and of the expected
average number of quality-adjusted life-years (QALY). In this model, patients
were assumed to be seen at annual intervals by GPs for clinical examination and
serum cholesterol level measurement, to which a TSH, T3 and T4 serum measurement
was added. In the base-case analysis, TSH was measured every 5 years and, if
abnormal, T3 and T4 serum levels were also determined. Costs were analysed from
the perspective of the Italian National Health Service (NHS) and reflected 1996
values. MAIN OUTCOME MEASURES AND RESULTS: In the base-case analysis, the
additional benefit estimated from testing a female population for subclinical
hypothyroidism every 5 years was 0.36 QALY, with a cost per QALY gained of
668,298 lire (L). The expected gain in QALY for men was 0.20 and the cost per
QALY gained was L270,322. In general, the best cost-effectiveness profile was
seen with testing every 3 years. Results were sensitive to variations in the
prevalence of disease among the target population, both in men and women.
CONCLUSIONS: Our study indicates that a screening policy for subclinical
hypothyroidism in the elderly population could be worthwhile. However, as the
costs could be significant when applied at the population level, this policy
deserves further assessment through well-designed primary research.
PMID- 10186462
TI - Pravastatin. A pharmacoeconomic review of its use in primary and secondary
prevention of coronary heart disease.
AB - Coronary heart disease (CHD) is a major cause of death and illness in
industrialised countries. Like other hydroxymethylglutaryl coenzyme A (HMG-CoA)
reductase inhibitors, pravastatin reduces total and low density lipoprotein (LDL)
cholesterol levels and increases high density lipoprotein (HDL)-cholesterol
levels. Cholesterol modification with pravastatin in middle-aged
hypercholesterolaemic men without CHD (i.e. primary prevention) was shown in the
West of Scotland Coronary Prevention Study (WOSCOPS) to reduce the incidence of
fatal and nonfatal coronary events. In several other large studies, pravastatin
reduced the incidence of CHD events in patients with prior CHD (secondary
prevention). Large, long term studies of the relationship between cholesterol
modification and CHD event rate have been conducted for some, but not all, other
HMG-CoA reductase inhibitors. A UK pharmacoeconomic analysis of the WOSCOPS data
indicated that primary prevention with pravastatin was associated with a cost of
20,375 Pounds per year of life gained (YLG) [discounted]. Treatment of men at
high risk for CHD resulted in a lower cost estimate (13,995 Pounds/YLG). A US
economic analysis based on secondary prevention with pravastatin in large plaque
regression studies suggested a net cost of drug therapy of $US7124 to $US12,665
per YLG. A number of projected-risk models have attempted to calculate the cost
effectiveness of primary or secondary prevention with pravastatin compared with
other lipid-modifying interventions. These comparisons indicated that pravastatin
was economically superior to intensive lifestyle counselling without drug
therapy. Pravastatin generally appeared to be less cost effective than other HMG
CoA reductase inhibitors, although the relative effectiveness of the various
drugs depended on the model considered. Risk-projection economic models are
subject to methodological limitations, principally the necessity of estimating
clinical effectiveness from epidemiological data (often derived from the
Framingham Heart Study). An increased absolute risk of CHD improves the cost
effectiveness of lipid-lowering therapy. Thus, the cost per YLG of pravastatin in
secondary prevention is, in general, lower than that of primary prevention,
reflecting the higher absolute risk of second versus first CHD events. However,
it is important to note that individual absolute risk rates may overlap between
patients receiving primary and secondary prevention. Similarly, treatment of
selected individual patients at high risk for CHD events is associated with a
lower cost per YLG than unselected treatment. CONCLUSION: In large clinical
studies, pravastatin effectively reduced the risk of primary and secondary CHD
events. These benefits come at a substantial economic cost, but one that is in
line with accepted costs for other medical interventions. Selective treatment of
patients or populations at high risk of CHD events improves the cost
effectiveness of pravastatin therapy.
PMID- 10186463
TI - The need for pharmacoeconomic evaluations in the NHS.
AB - New medicines can be cost effective, and the under use of many therapeutic
advances has been a cause for concern. Equally, the introduction of certain
expensive products onto the market prematurely where adequate clinical studies
have not been conducted equally represents an unsatisfactory situation. Many of
these products that have reached the market 'too soon' have been for serious
conditions where current treatments are inadequate and the new product represents
a new hope which may or may not be realised. For some products, studies may have
to take place after marketing and a condition for patients receiving treatment is
that they are enrolled into a postmarketing study. Ultimately, decisions on the
use of such treatments should be made after adequate clinical efficacy studies
are available and independent pharmacoeconomic assessment has taken place.
Decisions on the use of expensive treatments should be made nationally and not
left to local health authorities desperate to balance their budgets.
PMID- 10186464
TI - Methodological quality of economic modelling studies. A case study with hepatitis
B vaccines.
AB - The notable increase in the quantity of economic evaluations in the last 2
decades has not been matched by good methodological standards. This problem is
particularly evident in the field of economic evaluations of hepatitis B
vaccines. The results of 2 systematic reviews conducted by us in 1993 and 1996
showed three problem areas. A sizeable minority of study reports failed to
provide a clear study aim, showing a basic ignorance of the first rule of
conducting scientific research. The basic epidemiological assumptions upon which
the economic models were based showed variability which persisted even after
stratification, raising the question of the accuracy of the epidemiological
knowledge base of hepatitis B infection and its progression. Lastly, many of the
studies showed weaknesses in basic methods of conducting and reporting economic
evaluations. Examination of these problem areas led us to conclude that no
conclusions about the efficiency of hepatitis B vaccines could be drawn from the
available evidence. Addressing the problem of poor methodological standards
concerns the whole research community. However, as a proportion of economic
evaluations are published, one obvious means of exerting pressure to increase and
maintain methodological standards is the editorial and peer review process.
Editors of specialist and general medical journals should agree on and enforce
common explicit guidelines for study conduct and reporting, following the example
of the British Medical Journal.
PMID- 10186465
TI - Reporting format for economic evaluation. Part II: Focus on modelling studies.
AB - This article presents the first version of a reporting format for modelling
studies which is based on a general reporting format by our taskforce, which was
published in the previous issue of this journal. The use of decision-analytical
models for economic evaluations is increasing because, in practice, it is not
always possible to derive information from prospective studies. However, the
acceptance of modelling studies is generally lower than prospective studies not
only because of the use of secondary data, but also because the reports of
modelling studies do not always have sufficient transparency. Hence, a
standardised reporting format may improve the transparency and, consequently, the
acceptance of modelling studies. This article presents an example of a reporting
format for economic evaluation based on modelling studies, which may facilitate
the development of future guidelines for modelling studies. The format consists
of a number of headings, which are followed by a brief recommendation on the
content. This format does not deal with methodology and data management, but
especially addresses validation and quality assurance, which may increase the
transparency of the report.
PMID- 10186466
TI - Outcomes of pharmacological and surgical treatment for obesity.
AB - The purpose of this article is to review the data from pharmacotherapeutic and
surgical intervention studies for the management of obesity. Clinical outcomes
assessed include weight changes over time and the effects of weight loss on blood
pressure, serum lipid profiles and blood glucose control. Quality of life and
economic data have been incorporated where available. Double-blind, randomised
controlled trials were used preferentially over shorter term open studies. The
literature evaluation was based on a Medline search of published data between
January 1990 and January 1998. Obesity affects 65 million adults in the US.
Estimates based on 1990 data suggest that obesity and comorbid illness
contributed to $US46 billion in direct costs and $US23 billion in indirect costs
in the US. Obesity is a chronic condition which requires long term management.
The risk of developing cardiovascular disease, hypertension, type 2 (non-insulin
dependent) diabetes mellitus, osteoarthritis, Pickwickian syndrome and cancer is
increased in the obese population, resulting in excess morbidity and mortality.
There are no long term prospective studies that have demonstrated that weight
reduction in obese patients improves survival. However, on the basis of
epidemiological data using the prevalence of disease and associated body mass
index, it is generally accepted that weight reduction of 5 to 10% in obese
patients is associated with significant health benefits. Current treatment
modalities include diet and behaviour modification, exercise and, where
indicated, pharmacological intervention. Surgical intervention is reserved for
the clinically severe obese patient [body mass index (BMI) > 40 kg/m2]. Many
studies have demonstrated weight loss and improved metabolic fitness over 6 to 12
months. Few studies have been conducted over a longer period. Limited data are
available regarding reduced morbidity and mortality, improved quality of life and
functional or employment status and even fewer have incorporated any economic
assessments of the impact of medical or surgical intervention. Although
prospective data have demonstrated reduced morbidity following surgical
intervention, only retrospective data have demonstrated reduced mortality.
Studies of new drugs and interventions under development should demonstrate long
term safety and efficacy in terms of sustained weight loss and subsequent weight
maintenance. Future studies should incorporate assessment of patient perceived
satisfaction with weight loss, health status and quality-of-life evaluations and
pharmacoeconomic data to aid clinicians in the decision-making process in terms
of weight management of their obese patients.
PMID- 10186467
TI - Cost analysis of palliative care for terminally ill cancer patients in the UK
after switching from weak to strong opioids. Palliative Care Advisory Committee.
AB - OBJECTIVE: We constructed a UK-based decision model of palliative care for
terminally ill cancer patients who were switched from a weak to a strong opioid
so that the expected direct healthcare costs in the UK could be estimated from
the time a patient commenced a strong opioid until death. DESIGN: Decision
analysis techniques were used to estimate the expected total direct healthcare
cost per patient, stratified according to the first choice of strong opioid. The
model was based on prescription data on 1975 terminally ill cancer patients who
were on the Intercontinental Medical Statistics database, Mediplus (IMS Ltd,
Middlesex, England). Resource-use data were obtained from published literature, a
Delphi Panel and an advisory panel with expertise in palliative care. MAIN
OUTCOME MEASURES AND RESULTS: The expected cost of managing terminally ill cancer
patients after they switched from a weak to a strong opioid ranged from 2391
pounds sterling (Pounds) to 3701 Pounds at 1995/1996 prices, depending primarily
on the patient's duration of survival. Sensitivity analyses showed that the cost
could be as low as 1500 Pounds or as high as 6000 Pounds, depending on resource
use (at 1995/1996 prices). The key cost drivers were: hospice care,
hospitalisation, general practitioner (GP) consultations and specialist nurse
visits. In contrast, neither the choice of opioid nor managing constipation
impacted substantially on the expected cost. Approximately two-thirds of the
expected total cost was incurred by the UK National Health Service (NHS), with
the remainder incurred by voluntary and charitable sectors. Hospice care and
hospitalisation collectively accounted for between 50 and 80% of the expected
costs. Management of patients in the community by the primary healthcare team
accounted for between 10 and 40% of the costs. The acquisition cost of opioids
accounted for between 2 and 8% of the expected cost and discounting the cost of
these drugs sold to hospitals did not impact substantially on the total expected
costs. The use of other resources such as antiemetics, NSAIDS, antidepressants
and gastrointestinal drugs accounted for up to 3% of the expected cost.
CONCLUSION: The expected cost of palliative care in the UK healthcare setting
ranged from approximately 2500 Pounds to 4000 Pounds (1500 Pounds to 6000 Pounds
in the sensitivity analysis) depending on the length of survival after patients
switch from weak to strong opioids. Since opioids account for only 2 to 8% of
expected costs, factors other than economic issues, such as tolerability profile,
patient preference and convenience of use, should form the basis of clinical
decision-making between opioids with similar analgesic efficacy.
PMID- 10186469
TI - Cost effectiveness of immunoprophylaxis in the prevention of recurrent infectious
rhinitis in adults.
AB - OBJECTIVE: Recurrent infectious rhinitis (RIR) is a frequent disease among adults
and constitutes an economic burden for National Sickness Funds (NSF) that might
be prevented by immunostimulant therapy. Cost effectiveness of preventive methods
should be documented. The aim of this study was to determine whether the cost of
treating patients with ribosomal vaccine (Ribomunyl), an immunostimulant therapy,
could be offset by the savings associated with avoided RIR episodes. DESIGN AND
SETTING: Using a 'piggy-back' approach, an economic analysis was conducted based
on a placebo-controlled clinical trial of 327 patients with at least 3 episodes
of RIR in the past year. Patients were recruited during September and October
1994 through 50 French and 2 Belgian specialists (ear, nose and throat; ENT) and
were randomised to receive ribosomal vaccine or placebo for a 6-month period
covering the entire winter season. Two economic perspectives were analysed: (i)
the French NSF; and (ii) the patient (i.e., considering copayments which are not
reimbursed by the NSF). MAIN OUTCOME MEASURES AND RESULTS: The placebo-controlled
clinical trial demonstrated a significant decrease (p < 0.001) of more than 30%
in the cumulative number of RIR episodes with ribosomal vaccine during the 6
month study period. In general, patients receiving the active treatment tolerated
it well. Data were collected on the use of medical services (e.g. number of
physician visits), antibacterial and other drug courses, as well as the number of
sick-leave days for the study participant. Patients treated with ribosomal
vaccine visited their general practitioner (GP) less frequently (mean reduction
of 33%), had fewer days of antibacterial use (mean reduction of 3.5 days) and
took fewer sick-leave days (mean reduction of 6.3%). CONCLUSIONS: Overall, the
cost of prevention with ribosomal vaccine was offset by the savings to both the
French NSF and to patients (in terms of out-of-pocket expense). Indeed, ribosomal
vaccine was deemed to be a cost-saving agent in the prevention of RIR in the
French healthcare setting, provided that it is prescribed only for patients who
are expected to develop at least 2 episodes of RIR in the coming year.
PMID- 10186468
TI - The economic impact of Parkinson's disease. An estimation based on a 3-month
prospective analysis.
AB - OBJECTIVE: This study prospectively assesses the medical costs of Parkinson's
disease (PD). DESIGN: Over a period of 3 months (from July to September 1995),
patients with PD documented all items of healthcare provision. These data were
then used to calculate medical costs for an individual patient as well as the
costs of PD. PATIENTS AND SETTING: We included 20 outpatients with idiopathic PD
from the neurological outpatient clinic, Klinikum Grosshadern, Munich, and 20
patients from two office-based neurologists in South-West Germany. MAIN RESULTS:
The mean 3-month medical cost of PD in 1995 deutschmarks (DM) was 5210 ($US3390,
2240 Pounds) consisting of DM1410 ($US920, 610 Pounds) for care and nursing,
DM1580 ($US1030, 680 Pounds) for drug therapy, DM1320 ($US860, 570 Pounds) for
inpatient hospital care, DM40 ($US26, 17 Pounds) for outpatient care and DM860
for other expenses ($US560, 370 Pounds). The expenditure was related to the
disease evolution. Patients complaining of one-sided symptoms [Hoehn and Yahr
stage I; (HY I)] were less expensive to treat (DM1930, $US1250, 830 Pounds) than
patients who were severely incapacitated (HY V) [DM9740, $US6330, 4200 Pounds; HY
V]. After 3 to 5 years of levodopa treatment approximately 50% of patients start
to experience fluctuations in motor ability and dyskinesias [Unified Parkinson's
disease rating scale, part IV (UPDRS IV)]. This onset of motor complications
parallels an increase in costs. For patients who experienced motor fluctuations,
annual costs were DM6550 ($US4260, 2820 Pounds) compared with DM3030 ($US1960,
1300 Pounds) for patients lacking this problem. Indirect non-medical costs were
not calculated due to the limited number of patients. The impact of the disease
on work, however, is clearly apparent from the patients' history: 19 out of 34
patients who had already stopped working attributed this to the disease, and only
6 patients were still working at the time of the survey. CONCLUSION: PD poses a
major financial impact to society which is expected to increase in future years
as the age distribution shifts to older age groups. On the basis of a prevalence
of PD of 183 per 100,000, we calculated an annual expenditure of DM3.0 billion
for the direct medical costs of PD in Germany.
PMID- 10186471
TI - Managed care in Germany and Switzerland. Two approaches to a common problem.
AB - The point of departure for this contribution is a problem common to all Western
healthcare systems, namely the deficiency of their basic building block, the
physician-patient relationship. This deficiency opens up a market for
complementary agents in healthcare, ranging from medical associations to the
central government. While Germany has traditionally put the emphasis on medical
associations as the dominant complementary agent (DCA), it is shifting towards
the central government. Switzerland, on the other hand, traditionally has relied
on the cantonal governments and is now moving towards competing (quasi-) private
health insurers that would function as DCAs. Thus, managed care, which is a means
through which to reshape the physician-patient relationship, is used quite
differently in the 2 countries, with differing expected outcomes and different
consequences for the pharmaceutical industry.
PMID- 10186470
TI - Costs and effects associated with a community pharmacy-based smoking-cessation
programme.
AB - OBJECTIVE: The aim of the study was to determine the costs and effects associated
with a community pharmacy-based smoking-cessation programme in Northern Ireland,
using the perspective of the payer in the main analysis. DESIGN AND SETTING: Data
from a pilot study conducted in 2 community pharmacies in Northern Ireland were
used as the basis of the current study, which examined the cost effectiveness of
a formal counselling programme for smoking cessation by community pharmacists
throughout Northern Ireland. A number of assumptions were made in the baseline
analysis (e.g. annual rate of smoking cessation in the absence of the programme;
lifetime relapse rate), and these were varied in the sensitivity analysis.
PATIENTS AND PARTICIPANTS: The pilot study upon which the main analysis was based
was carried out in 2 Belfast pharmacies over a 2-year period. 52 people entered
the smoking-cessation programme (group 1), 48 bought nicotine gum and gave their
address so that additional information could be sent and they could be followed
up (group 2), and 60 people who expressed a wish to stop smoking were chosen on
the basis that they matched, by age, gender, social status and disease status,
those in group 1. Thirty-five of those in group 1 requested to use nicotine gum.
A statistically significant difference (p < 0.01) was found in cessation rates
between intervention and control patients. INTERVENTIONS: The Pharmacists Action
on Smoking (PAS) model was the only active intervention used in the study. The
model was developed by the PAS group in association with the National
Pharmaceutical Association (NPA) in the UK in 1994, and was designed specifically
for use by community pharmacists to provide advice and motivation to help smokers
stop smoking. The 4-stage model involves a written 'contract' between the patient
and pharmacist (including a 'stop date'), and a series of brief counselling
meetings over a period of approximately 6 months. MAIN OUTCOME MEASURES AND
RESULTS: Our findings indicate that the cost per life-year saved when using the
PAS programme ranges from 196.76 pounds sterling (Pounds) to 351.45 Pounds for
men and from 181.35 Pounds to 772.12 Pounds for women (1997 values), depending on
age. This compares favourably with other disease prevention medical interventions
such as screening for hypertension or hypercholesterolaemia. CONCLUSIONS: These
findings provide an argument for adoption and remuneration of the PAS model in
the community pharmacy (primary healthcare) setting.
PMID- 10186472
TI - How competition lowers the costs of medicines.
AB - This paper examines whether there are any economic advantages in allowing entry
to pharmaceutical markets at the manufacturers' risk and at prices of their
choosing. To examine this thesis, 6 countries (the US, the UK, Denmark, Holland,
Germany and South Africa) were chosen for study because they allow a degree of
free access and (varying) degrees of pricing freedom, at least to the extent that
new product prices are not directly controlled. In just about every other
European market, there are direct price controls on new products. The key finding
was that, in markets where there is some semblance of pricing freedom,
competition tends to keep down the price of medicines. Rival products serve a
useful purpose in containing market prices. Since innovative rivalry is a sine
qua non in pharmaceutical markets, this price-depressing competitive influence
should be allowed to have its full effect and not be distorted or suppressed by
regulation at the level of either the pharmaceutical manufacturer or the retail
pharmacist.
PMID- 10186474
TI - Parallel imports of pharmaceuticals in the European Union.
AB - Parallel importing has existed on a small scale in Europe for many years and has
been upheld by the European Court of Justice as consistent with standard
principles of free trade. However, the potential impact of parallel trade has
increased significantly with the launch of the European Medicines Evaluation
Agency in 1995, the accession to the European Union (EU) of countries with
traditionally low prices, such as Spain, and the possible accession of Eastern
European countries. This article examines the current state of parallel trade in
medicines in the EU (different modalities and the medicines affected), analyses
some policy implications associated with parallel trade (who gains and who loses)
and explores the effects of several policy scenarios affecting parallel trade.
The main conclusion is that a single European price is probably not the best
solution from a European welfare point of view. A solution to the present
situation could be achieved by separating the market price (at which any agent is
allowed to buy a product either for consumption or for resale) and the price
actually paid by a final consumer. Discounts and reference pricing may present
two of the most feasible options.
PMID- 10186473
TI - International price comparisons for pharmaceuticals. Measurement and policy
issues.
AB - Cross-national price comparisons for pharmaceuticals are commonly used for two
purposes. Comparisons based on a sample of products are used to draw conclusions
about differences in average price levels. Cross-national comparisons applied to
individual products are also used by governments to set domestic prices. This
paper examines the major methodological issues raised by international price
comparisons, focusing on measurement of differences in average price levels and
the validity of policy conclusions drawn from such price comparison studies. It
argues that valid measures of average price levels can only be obtained from
comparisons based on a comprehensive or representative sample of products,
appropriately weighted, following standard index number methods. Comparisons of
individual product prices should take into account the manufacturer's entire
product portfolio over time rather than focus narrowly on a single product at a
point in time. Because of the great variation across countries in both the range
of drug compounds available and the dosage forms, strengths and pack sizes for
each compound, obtaining a broadly comprehensive or representative sample is
problematical. If products are required to match on all dimensions, including
molecule, manufacturer, strength and pack, as is common in most international
price comparisons, then only a very small and unrepresentative sample of the
drugs available in each country can be included in the analysis. A trade-off
between the desire to compare only identical products and the need to compare a
truly representative sample of a country's pharmaceutical market is therefore
necessary. A valid comparison of average drug prices should include generics and
over-the-counter products that are good substitutes for branded prescription
drugs, with all forms, strengths and packs. To achieve this broad representation,
however, the requirements of same manufacturer, same brand, dosage form, strength
and pack size must be dropped. When such an approach is taken to the comparison
of international drug prices, quite different results from those obtained from
less comprehensive comparisons may be obtained. Indeed, a major conclusion of
this analysis is that international drug price comparisons are extremely
sensitive to choices made about certain key methodological issues, such as sample
selection, unit of measurement for price and volume, the relative weight given to
consumption patterns in the countries being compared, and the use of exchange
rates or purchasing power parities for currency conversion. In particular, the
results of this analysis indicate that recent reports suggesting that
manufacturer prices in the US are 32% higher than in Canada and 60% higher than
in the UK are in fact overstatements which arise from limitations of the sample
and methods used to calculate these price differentials.
PMID- 10186475
TI - Is price regulation necessary? A summary of the arguments.
PMID- 10186476
TI - Defining our future work.
PMID- 10186477
TI - The role of cost-effectiveness analysis in managed-care decisions.
AB - This article considers the role of cost-effectiveness studies in the formulary
and disease-state management decisions of managed-care entities. In a recently
published symposium volume [Soc Sci Med 1997; 45 (4): 505-647], US managed-care
entities were found to be among the leaders in applying cost-effectiveness
studies to healthcare decisions. At the same time, a number of barriers were
identified that hinder their wider usage in the managed-care sector. These
factors are analysed in this paper along with the prospects for future changes.
The potential roles for government policy in this area are also discussed in the
final section of the article.
PMID- 10186478
TI - The emergence of managed care in Europe. Some thoughts on the politics of
healthcare reform.
AB - It is the purpose of this paper to demonstrate that healthcare reform in Europe
can be successful only if it leads to more efficient resource use while
maintaining a large degree of equity in the system. Globalisation is undermining
the social contracts that established Europe's egalitarian societies after World
War II. While socialised healthcare will continue to be an essential building
block of social cohesion, public expenditures must be contained. The only
approach to maintaining equity of access and financing in the face of a mounting
resource constraint is to embark upon a radical re-engineering of the entire
healthcare supply chain, introducing and adapting proven US managed-care
techniques to the European environment. Through enabling legislation, most
European countries are in a phase of testing the feasibility, cost effectiveness
and quality enhancement potential of managed-care approaches, before applying
them more broadly. While political opposition to change on the part of those
whose current positions are threatened continues to run high, the practice of
medicine can be expected to converge on the basis of standards of care and
information technology over the next 10 to 15 years.
PMID- 10186479
TI - Healthcare and the tooth fairy. A merger that won't result in 'smarter' medicine.
PMID- 10186480
TI - The evolution of managed care in the US.
PMID- 10186481
TI - Changes in the healthcare system. Goals, forces, solutions.
AB - The goals of a health system should be to provide all necessary care to
everybody, improve the mean level of quality of care, reduce variations in this
care, and eliminate waste. In fact, the driving force currently promoting change
in the health system is cost containment, and the greatest efforts being exerted
in this regard are in those areas where the most money is being spent. Research
suggests that increased health spending does not necessarily equate with improved
healthcare. Furthermore, reducing expenditure does not ensure that only less than
necessary procedures are eliminated. Thus, it is important to use a conceptual
model that relates cost to quality of care when approaching the problem of
reducing the costs of healthcare. It is also necessary to define quality of care
and necessary care, so that the clinical process can be re-engineered to ensure
that both quality and necessary care can be delivered. The financial incentives
that support the implementation of this process can then be put in place. Quality
of care at an acceptable cost can only be obtained if waste is identified and
eliminated, resources are applied to necessary and appropriate care, variations
in the quality of care are eliminated, and economic policies consistent with a
country's culture and expectations of value for money are adopted. Accomplishing
these objectives will be difficult and costly. However, the effort must be made,
if for no other reason than that the existing system in the United States,
whereby health insurance is not provided for everyone, is unacceptable.
PMID- 10186482
TI - Pharmacy benefit management companies (PBMs). Why should we be interested?
AB - Over the past decade, pharmaceutical benefit management companies (PBMs) have
assumed an expanded role as intermediaries in the design and administration of
pharmacy programmes. PBMs now provide a range of sophisticated, clinically
oriented services that increasingly influence physicians' prescribing patterns
and patients' access to pharmaceuticals. This paper reviews the nature and extent
of this new level of intervention that has a tendency to centralise the
prescribing and dispensing functions. The terms of engagement between PBMs and
pharmaceutical firms that own or do business with PBMs have provoked inquiries
and oversight by a number of federal government agencies, including the Food and
Drug Administration (FDA). In January 1998, the FDA published a proposed
guideline with implications for PBM promotional activities and the drug companies
that influence those promotions. The paper concludes with an overview of
potential liability issues relevant to the new functions and relationships of
PBMs.
PMID- 10186483
TI - Medicaid's transition into managed care. Real or imaginary?
AB - Medicaid provides health coverage for America's poorest citizens. The number of
persons enrolled in Medicaid represents 15% of America's population. The
percentage of the Medicaid population in managed-care organisations has risen
from 8% in 1990 to 50% in 1996. However, only 8% of the Medicaid programme
expenditures on pharmaceuticals is directed to the 50% of the Medicaid population
in managed care. Furthermore, more than half of this 8% occurs in loosely
organised managed-care organisations that do not have formularies or other
significant restrictions on pharmaceutical utilisation generally found in health
maintenance organisations. The reason that a larger proportion of Medicaid
programme expenditures does not occur in managed-care organisations relates to
the difficulty of enrolling the elderly and disabled in such organisations.
Barring significant new Federal legislative changes, less than 24% of Medicaid
programme expenditures will be in managed-care organisations by the year 2000.
Medicaid's transition into managed care is therefore more imaginary than real
when one focuses on expenditures.
PMID- 10186484
TI - The drug market in four European countries.
AB - Prescription drugs should be therapeutically validated products which are
selected for the treatment of accurately diagnosed diseases according to the
principles of evidence-based medicine. However, industrial promotion of
pharmaceuticals has meant that drug prescription patterns are not always
concordant with these ideals. For example, consideration of the most sold drugs
in 4 European countries--Italy, France, Germany and the United Kingdom--in 1992
and 1996 shows that marked variations in the utilisation of therapeutic classes,
single active principles, and even routes of administration of the same active
principles exist in these countries. To some extent, these differences reflect
the influence of promotion by national pharmaceutical companies, but they also
arise from other factors, such as the lack of adequate pharmacological training
of physicians, the paucity of reliable comparative clinical data to allow
clinicians to distinguish between large numbers of more expensive 'me-too' drugs
and their prototypes, and the idiosyncrasies of national drug approval and
registration systems. In addition, differences in prices across countries as well
as the length of time a drug has been on the market may be contributing factors.
It is hoped that the creation in 1995 of the European Medicines Evaluation Agency
(EMEA), which is working towards centralisation of drug marketing approval in the
European Union (EU), will usher in the establishment of a common pharmaceutical
culture that will combat some of the variations and inconsistencies in drug
prescribing patterns evident in European countries. Adoption of such evidence
based and more rational prescribing patterns should not only reduce the number of
unnecessary and perhaps undesirable prescriptions written for patients but also
relieve the financial burden on national health services in EU countries.
PMID- 10186486
TI - Pharmaceutical cost containment and quality care. Conflict or compromise?
AB - Existing methods of pharmaceutical cost containment are relatively primitive
weapons of expenditure restraint. Their effectiveness is generally limited to
short term savings. The conflict between cost containment and quality is
epitomised by the 'Drug Budget', which conditions payers to regard
pharmaceuticals solely as a cost input without considering the results of their
use in terms of integrated health outcomes, crossing the budgetary boundaries
between drugs, hospitals, ambulatory and other forms of healthcare. A further
problem, also related to the separation of inputs from outcomes, is the
contention by healthcare payers that, even if 'expensive' innovative drugs offer
Value for Money, budget holders cannot afford the required Money for Value. The
limits of affordability are real in poor countries. In rich industrialised
nations, the affordability of quality is in essence a political rather than an
economic issue. In making choices and determining priorities, elected governments
are usually responsive to public opinion, which is coming to regard the issue of
quality in healthcare as one of the highest social priorities. Pharmaceutical
innovation has much to contribute to quality in healthcare. A compromise between
pharmaceutical cost containment and quality is feasible, based on input/outcome
considerations, rational drug pricing, and re-engineering decision-making by
payers away from the simplistic notion that the cheapest drug budget is
necessarily the best.
PMID- 10186485
TI - Pharmaceutical policies in Canada. Issues and challenges.
AB - Prescription and over-the-counter medications are an important and widely used
part of healthcare in Canada. Such drugs represent an increasing proportion of
total healthcare expenditures. The objectives of the paper are to examine
pharmaceutical expenditures and utilisation in Canada, review the major cost
control strategies for pharmaceuticals, and discuss the future issues and
challenges for pharmaceutical policy in Canada. Compared with other Organisation
for Economic Cooperation and Development (OECD) countries, Canada (until
recently) has not been successful in controlling the rate of increase of
healthcare expenditures and, more specifically, pharmaceutical costs. The key
variables associated with high rates of increase in drug costs relate to
increased per capita use of drugs, use of more expensive drugs, and rising prices
of existing drugs. If policies are going to address the fundamental societal
issues behind both the price and utilisation elements of pharmaceuticals, policy
makers and third-party payers in Canada will probably have to focus, primarily,
on manufacturers and major healthcare providers and, secondarily, on consumers.
They will need to develop an internally valid package of consistent policies.
PMID- 10186487
TI - Why medical care costs in Japan have increased despite declining prices for
pharmaceuticals.
AB - Analysis of the 1979 to 1993 surveys of national claims data shows that, using
deflated prices, most of the increase in outpatient care costs is due to drugs,
with increases in gross volume and deflated unit prices making equal
contributions. Further analysis of detailed prescriptions data obtained from one
tenth of the total sample for 1991 and 1993 reveals that new drugs and originator
drugs tend to be selected more often. The present vicious cycle of high launch
prices, followed by subsequent cuts in the fee schedule, has led to adverse
consequences for the industry, physicians and patients.
PMID- 10186488
TI - Swallowing topically administered 4% lidocaine results in nausea and vomiting.
AB - In preparing adult volunteers for insertion of an upper airway device, we
observed a high incidence of nausea and vomiting in the first 16 consecutive
volunteers who were allowed to swallow topically administered 4% lidocaine (50%
and 31%, respectively). We tested the hypothesis that swallowing the topically
administered 4% lidocaine caused the nausea and vomiting by comparing the
incidence of nausea and vomiting in these first 16 volunteers with the incidence
of nausea and vomiting in the next 162 consecutive awake adult volunteers who
were not allowed to swallow the 4% lidocaine. All 178 volunteers were prepared by
administering 2 mg midazolam and 100 micrograms fentanyl intravenously, spraying
10 to 15 mL of 4% lidocaine into the upper airway, and bilaterally blocking the
lingual branch of nerve IX and the superior laryngeal branch of nerve X. The
first 16 volunteers were allowed to swallow the 4% lidocaine (swallow/no suction,
group A); the next 162 volunteers were not allowed to swallow the 4% lidocaine,
and all of the 4% lidocaine was suctioned out of the upper airway (no
swallow/suction, group B). Groups A and B were otherwise and subsequently treated
identically. The incidence of nausea and vomiting in group A was 50% (8/16) and
31% (5/16), respectively, and in group B, 4% (7/162) and 1% (2/162),
respectively. The difference in the incidence of nausea and vomiting between
group A and group B was highly significant by chi-square analysis (P < 0.01). We
found that swallowing topically administered 4% lidocaine results in a
significant increase in the incidence of nausea and vomiting. Our experimental
design did not allow us to rule out either of two basic mechanisms, higher blood
levels and a direct toxic effect, or to distinguish between them. The clinical
implication of this study is that suctioning all topically administered 4%
lidocaine will decrease the incidence of nausea and vomiting.
PMID- 10186489
TI - Friendliness of OR staff is top determinant of patient satisfaction with
outpatient surgery.
AB - Two hundred patients (151 women) undergoing outpatient surgery at a university
hospital were asked to complete a questionnaire at the time of discharge. Listing
12 factors related to preoperative intraoperative, and postoperative care, the
questionnaire asked each respondent to rank the five most important factors from
1 to 5. The most important factor, ranked among the top five by 67% of the
patients, was friendliness of the operating room staff. The other four (and,
parenthetically, the percentage of patients ranking the factor among the top
five) were as follows: surgeons's postoperative visit (63%); management of
postoperative pain (62%); starting i.v. smoothly (53%); and avoidance of delays
(45%).
PMID- 10186490
TI - Iontophoresis: noninvasive drug delivery.
AB - Iontophoresis allows for the transdermal delivery of charged drugs under the
influence of a low-level electric current. Recently iontophoretic technology has
been used to deliver lidocaine to provide rapid, noninvasive local anesthesia.
Studies have also demonstrated the ability to obtain systemic opiate levels using
this technology. In this article we review the history and principles of
iontophoresis as well as the literature supporting its use for both local
anesthesia and systemic analgesia.
PMID- 10186491
TI - Proceedings of the 2nd International Conference on Gerontechnology. Helsinki,
Finland, October 1996.
PMID- 10186492
TI - Ethics and gerontechnology: a plea for integration.
PMID- 10186493
TI - Shade-tree psychophysics: models, mathematical and concrete, for the simulation
of ageing.
PMID- 10186494
TI - Future society and technology.
PMID- 10186495
TI - Primary proprioceptive reactions on perturbations at foot level.
PMID- 10186496
TI - Age-related effects on cognitive processes: application to decision-making under
uncertainty and time pressure.
PMID- 10186497
TI - Visual capacities of the elderly, relevant to man-product interaction, assessed
in the Delft Gerontechnology Project.
PMID- 10186498
TI - Modelling age differences in the interaction with new technology.
AB - A descriptive framework was developed to describe the problem-solving behaviour
of young and old subjects when they learn to use a new interactive device. The
model distinguishes three levels of problem-solving that are thought to differ
with respect to the cognitive load they pose to the user. Given a higher number
of inputs by young subjects, protocol analysis shows elderly subjects to perform
more actions on the level of low cognitive load, and less on the level of high
cognitive load. Across age groups experience serves mostly to decrease the less
purposeful behaviour.
PMID- 10186499
TI - Proposals and solutions for autonomy of the disabled and elderly.
AB - The aim of this paper is to present DEFIE (Disabled and Elderly people Flexible
Integrated Environment) a project of the CEC to develop a multimedia integrated
system that allows the elderly and motor and/or sensory impaired to command and
control domestic and working environments with a high degree of self-sufficiency
and safety. The goal of this study has been to implement a precompetitive
prototype of a modular system capable of satisfying the needs of a heterogeneous
group of disabled and elderly users.
PMID- 10186500
TI - Multisensor system and artificial intelligence in housing for the elderly.
AB - To improve the safety of a growing proportion of elderly and disabled people in
the developed countries, a multisensor system based on Artificial Intelligence
(AI), Advanced Telecommunications (AT) and Information Technology (IT) has been
devised and fabricated. Thus, the habits and behaviours of these populations will
be recorded without disturbing their daily activities. AI will diagnose any
abnormal behavior or change and the system will warn the professionals.
Gerontology issues are presented together with the multisensor system, the AI
based learning and diagnosis methodology and the main functionalities.
PMID- 10186501
TI - First experiences with using E-mail and Internet by elderly living in sheltered
housing.
PMID- 10186502
TI - Implementation of assistive technology in the homes of well older people.
PMID- 10186503
TI - Technologies to support carers.
PMID- 10186504
TI - Technology to help family carers: innovative U.S. dissemination strategies.
AB - Life could be easier, safer, and more independent for millions of older Americans
if their homes were better suited to their changing needs. The most common less
felt by those growing older can be compensated for to some degree through the use
of technology products and or home modification. Most older adults noting
difficulty in routine activities attribute the cause to physical change within
their own body. The older adult or carer rarely considers the fact that the home
itself or the tools chosen for activity performance may be exaggerating an
individual's changing abilities. Implementation of the programs described in this
paper increase community education potential. Consumers, carers, and service
providers can better recognize the utility of technology as a strategy for more
successful aging.
PMID- 10186505
TI - Telematics for the integration of disabled and elderly people--technology to help
family caregivers--interesting innovations from the United States.
PMID- 10186506
TI - User requirements in telematic projects--a task for Sisyphus.
PMID- 10186507
TI - Telephone services as addition to home care services helping elderly people.
PMID- 10186508
TI - Videotelephony-based services--the proven improvement of quality of life.
AB - As described above, the research activities showed very promising and fascinating
results. It could be observed that the presumed acceptance problems of elderly
technology users are not larger than in other groups. What is more: the elderly
user of videotelephony-based services is a very pragmatic user. He or she accepts
the new service offer as long as he or she sees the benefits. Decision makers in
the social field should not be afraid of this client group! All of the users were
willing to pay for the service--up to three times their current communication
costs. It seems that there is a market for both the network providers and the
telecommunication manufacturers. Private social service provider organisations
were the first to realise the potential of the videotelephony-based social
support and care services. Some of them are already developing service design
schemes and are eagerly awaiting affordable technology. To ensure equal
accessibility to these kind of services financial support is necessary to address
the needs of socially disadvantaged user groups. Moreover, policy makers should
concentrate on the definition of quality requirements for different issues. At
the same time, neutral control institutions have to be set up to overcome
prejudices and prevent misuse. All in all the authors still believe that picture
based social support and care services are one solution for the increasing
problems resulting from demographical and social changes in many industrial
societies. The technical evolution and the rapidly decreasing costs will lead to
the implementation of picture-based social support and care services within a
very short time. Some large application projects are currently underway
throughout Europe. What is more: in Frankfurt/Germany, for instance, the first
commercially available picture-based service will be introduced to the public in
the spring of 1997.
PMID- 10186509
TI - Videotelephony as a tool for recreation programming for elderly people.
PMID- 10186510
TI - Telecommunication technology for the elderly and other vulnerable groups in
Slovenia.
PMID- 10186511
TI - Mobility of elderly persons in time and space in The Netherlands: flexible public
transport for the elderly.
PMID- 10186512
TI - The outdoor mobility of elderly people--a comparative study in three European
countries.
PMID- 10186513
TI - The perception of traffic conditions by elderly people. A comparative study in
three European countries.
PMID- 10186514
TI - The Drive II: elderly and disabled drivers information telematics (EDDIT)
project: could new telematic systems really help elderly drivers?
PMID- 10186515
TI - Intelligent transportation systems: gerontechnological interventions.
PMID- 10186516
TI - Residential behaviour of the elderly: an explanatory analysis for The
Netherlands.
PMID- 10186517
TI - Ageing in the information society: a European perspective.
PMID- 10186518
TI - Turtle: a prototype, real time, public transport information system focused on
the needs of disabled older people.
PMID- 10186519
TI - Strength profiles of older persons.
PMID- 10186520
TI - Parameters of spinal forms during sitting. Part of the Delft Gerontechnology
Project.
AB - In this paper the development of a measuring method is described. The subject of
the ultimate study is the exterior form of the spine, which is a very complicated
bodily element. In order to find out whether particular forms exist in
combination with specific postures of the body or whether age influences the
spinal form and flexibility, this research was done. Because this research is
based on recently developed analysing method, this method was put to test first.
PMID- 10186521
TI - Quantifying quality of moving in the elderly based on ambulatory accelerometry.
PMID- 10186522
TI - Age, absenteeism and physical fitness in relation to work ability.
PMID- 10186523
TI - Keeping the elderly at home.
PMID- 10186524
TI - The balance of care.
PMID- 10186525
TI - Nutritional problems of demented elderly people.
PMID- 10186526
TI - Preliminary results of the specification of the functional requirements of the
PLANEC system. PLANning of Elderly Care.
PMID- 10186527
TI - Experiments of an iterative software development process--a software engineer's
point of view.
PMID- 10186528
TI - Community care and "gerontechnology".
PMID- 10186529
TI - Fully automated health monitoring at home.
AB - The aim of this study was to provide adequate home health monitoring for the
elderly at home using fully automated signal measurement with personal
identification to support daily health care and to improve quality of life. We
attempted to develop a home health monitoring system that did not provide any
restrictions during sleep, bathing and excretion. A new room including bath and
toilet was constructed. The system consisted of monitoring devices and a computer
terminal for collecting data. The data were automatically obtained from
monitoring devices situated at the bed, bath and toilet and were transferred to a
data terminal and stored for further analysis. Where subjects live with their
spouse or family, personal identification is required to store data individually.
For the bathtub data, personal identification was performed using ECG data.
Sampled data were reduced by wavelet transform and distinguished by a neural
network. The data acquisition system is now underway and data are being
extensively collected.
PMID- 10186530
TI - Method and computer technology for creating psychological support and propaganda
of healthy and life-span-increasing nutrition.
PMID- 10186531
TI - Human factors engineering approach to gerontechnology: development of an
electronic medication compliance device.
PMID- 10186532
TI - The place of elderly people in a changing social and economic environment:
perspectives from social science.
PMID- 10186533
TI - Quantifying the potential for independent living in COPD-patients.
AB - In patients with Chronic Obstructive Pulmonary Disease (COPD), daily physical
functioning as quantified by energy expenditure, is limited by decreased
ventilatory capacity and increased basal metabolic rate in relation to their
physical capacity. Starting from the Dutch Health-Care situation, a measurement
interpretation model is presented to quantify individual potential for
independent living from energy expenditure, aerobic capacity and lung function.
The interpretation model concerns only simple routine measurements. After further
validation, this model will be used in predicting the clinical effects of
environmental improvements.
PMID- 10186534
TI - Gerontechnology. A sustainable investment in the future.
PMID- 10186535
TI - Do technical aids affect the use of home care or institutional care?
PMID- 10186536
TI - Users' experiences--the basis for better quality nursing environments in long
term care.
PMID- 10186537
TI - Use and effectiveness of homecare technology for the elderly.
PMID- 10186538
TI - Evaluation of effectiveness of rehabilitation in elderly patients with ischaemic
heart disease.
PMID- 10186539
TI - Organizational culture as an instrument in residential care for dementing
elderly.
PMID- 10186540
TI - Technology in everyday life and care of elderly living at home and suffering from
dementia.
PMID- 10186541
TI - Home care for the elderly with dementia. A social shaping approach to a multi
media-PC application.
PMID- 10186542
TI - Technology for dementing persons: a relief for informal carers?
PMID- 10186543
TI - A model house as platform for information exchange on housing.
PMID- 10186544
TI - Adaptive problem solving processes of older persons in their homes.
PMID- 10186545
TI - Living environment and autonomy in residential and service homes.
PMID- 10186546
TI - The living environment of home care patients: an exploration of the GIFT data.
PMID- 10186547
TI - Twice as many years as our ancestors: and the concept of a life plan.
PMID- 10186548
TI - Safety for the elderly by improving the environment?
PMID- 10186549
TI - The role of elderly panels in the design process of new products for the
bathroom.
PMID- 10186550
TI - The effects of a cognitive training on mobility of elderly people.
PMID- 10186551
TI - A training programme to improve the driving performance of elderly drivers.
PMID- 10186552
TI - Government policy and the provision of training for older workers.
PMID- 10186553
TI - Gerontechnology in higher engineering education.
AB - This paper is based on experiences with designing an educational programme on
gerontechnology at Eindhoven University of Technology (TUE) and designing and
developing various international gerontechnology courses. There are two major
goals for education in gerontechnology: (1) creation of a knowledge base of
principles, methods and facts about ageing and technology; (2) creation of an
attitude base about the convictions, beliefs and goals for society that are
embedded in the concept of gerontechnology. Because the knowledge base of
gerontechnology is multi-disciplinary, an outline for a curriculum has been
developed that consists of four basic modules: (1) basic concepts, (2)
information about people, (3) information about technology and (4) macro aspects.
Project-oriented education as educational method is an attractive tool for
teaching gerontechnology and the creation of an attitude base. Project-oriented
education is an organisational format in which the students collaborate as a team
on a case they chose themselves. Relevance to society is a leading factor for the
formulation of the cases. This often requires a multi-disciplinary approach. A
case-study as such provides a context for integrating disciplines, theory and
practise. Besides the two major goals, the courses intend to increase the
interest of students in participating in ongoing research projects on
gerontechnology. This all stimulates the further development of gerontechnology.
PMID- 10186554
TI - How to enhance acceptance of safety alarm systems by elderly?
PMID- 10186555
TI - Product safety requirements for elderly--an interim report.
PMID- 10186556
TI - Safety and indoor mobility in the elderly.
AB - The aim of this study was to find the basis for developing and adapting the
environment to support the easy and safe moving of the elderly. In the field
study, the daily activities and previous falls were inquired, the performance of
the elderly was examined and the safety of the residential environment was
surveyed among 70-80 years old subjects (N15). The second part was performed in
the laboratory. 70-80 years old subjects (N55) walked on the test track. The risk
level of most houses studied was moderate. In the residential surveying, all
subjects had problems to stretch to high levels and most had problems to stretch
to low levels. In the laboratory, errors happened often during line walking and
zigzag walking in the stick track. Unsteadiness in gait was caused by extra
pieces on the track and box carrying in one third of the subjects. The old
subjects estimated that stairs somewhat lower than normally recommended were
easier to climb. The results indicated, that new criteria and regulations are
needed for the residential environment for the elderly and that it is possible to
improve the safety of indoor mobility among the elderly in many ways.
PMID- 10186557
TI - Security alarm system supports independent living of demented persons.
PMID- 10186558
TI - Transgenerational design of "smart products", a checklist of guidelines. Part of
the Delft Gerontechnology Project.
AB - Elderly users have been observed using their own appliances and consumer
electronics in their homes. From this, design guidelines have been derived,
focussing on the durables as well as their manuals. The guidelines consist of
recommendations for design methods, requirements for manuals and product
requirements, mainly concerning usability.
PMID- 10186559
TI - Attitudes on technical devices among the elderly, aged 74 years or over.
PMID- 10186560
TI - Interface assessment: elderly users of an interactive television system.
AB - Assessment of an interactive television service has highlighted potentially major
barriers regarding the ease and desirability of access by elderly users. The
kinds of service available through such technology vary widely as do the
interaction operations required to achieve the goal of each service. For many
interfaces, in particular those in the workplace, some element of explicit
training or extended practice may be necessary and appropriate to achieve
proficient use. However, in order to attract paying customers to television based
interactive services, the expectation should be of a rapid and fairly effortless
route to proficiency. Evidence is presented which indicates no positive effects
of previous experience with a combined set of interactive services and it is
argued that this is mainly due to a lack of explicit information and to
inconsistencies (mainly between service providers) in the operation rules (both,
explicit and implicit) provided.
PMID- 10186561
TI - Evaluation of communication device: an aphasia case study.
PMID- 10186562
TI - Design participation by the thousand elders.
PMID- 10186563
TI - Inspiring the young.
PMID- 10186564
TI - Innovations in the clothing for the elderly.
PMID- 10186565
TI - Textiles for disabled and elderly people--Easytex.
PMID- 10186566
TI - Social or technical perspectives--does it matter?
PMID- 10186567
TI - Current situation and future plan of action of community-based programme for
health of the elderly in China.
PMID- 10186568
TI - Old people are people: the need to prepare in fiscal and non-fiscal areas.
PMID- 10186569
TI - The elderly as consumers--an argument on the elderly.
PMID- 10186570
TI - Transformation of care of the aged among Africans--a study of Kenyan situation.
PMID- 10186571
TI - Ageing and technology--an innovative model in Hungary.
PMID- 10186572
TI - The health and welfare of the elderly in St. Petersburg.
PMID- 10186573
TI - Diffusion and acceptance of technological solutions among the elderly in three
European countries.
PMID- 10186574
TI - Individual and collective ageing and technological developments: a French social
sciences research programme.
PMID- 10186575
TI - Maintaining movement ability in old age: challenges for gerontechnology.
AB - The degree of behavioral slowing that occurs with aging is highly task specific.
Compensation for age related slowing, when necessary, requires task redesign and
ergonomic interventions. Walking, performing various physical chores required in
carrying out ADLs and IADLs, and avoiding falls are challenges for significant
numbers of old people. Interventions based on prevention and/or compensation were
presented. Approaches to the maintenance of strength required to carry out such
activities emphasized resistive training programs. Improvements in visibility of
the physical environment were stressed as one means of reducing falls and
accidents.
PMID- 10186576
TI - Ergonomics and ageing: the role of interactions.
PMID- 10186577
TI - Improving the quality of life for older people by design.
AB - In this paper it is argued that design has an important role to play in
developing age-friendly products and services, and in particular in ensuring that
mainstream products and new technologies respond to and meet the needs of older
people. There are already many examples of good and appropriate design, and the
philosophies, methodologies and strategies that are needed are largely in place.
In order to put these concepts into practice on a significant scale the value of
design as applied research should be recognised, and designers brought into
research and development programmes and projects from the very beginning. The
concept of 'critical users' is introduced and it is argued that working with
older users can act as a spur to innovation and improvements in products and
services. Technology should serve people, and the needs of older people will best
be served by regarding them as consumers and including them in the research and
development process. Just as design should be an integral part of
Gerontechnology, the principles of Gerontechnology should become an integral part
of design education.
PMID- 10186578
TI - Design slippage over the life-course.
PMID- 10186579
TI - Gerontechnology: emerging technologies and their impact on aging in society.
PMID- 10186580
TI - Primary care recruitment slows; family practice remains on top.
PMID- 10186581
TI - Do you have a year 2000 problem?
PMID- 10186582
TI - Demand management: implementing your own program.
PMID- 10186583
TI - Demand management: the patient education connection.
PMID- 10186584
TI - The impact of health care reform on local health departments.
PMID- 10186585
TI - Health system reform: a blueprint for the future of public health.
AB - As the state of Washington formulated its health reform legislation, public
health successfully advocated for its inclusion as integral to successful reform.
The blueprint for public health's role within health reform is The Public Health
Improvement Plan. The plan describes standards for the infrastructure and
performance required to carry out the core functions of public health. It
contains outcome standards, threshold standards, and interventions for key
problems currently affecting the health status of Washington residents. The plan
also recommends the shared financing and governance responsibilities for public
health functions within a reformed health system.
PMID- 10186586
TI - The forest of data.
PMID- 10186587
TI - Who will provide preventive services? The changing relationships between medical
care systems and public health agencies in health care reform.
AB - Health care reform in the United States will likely attempt to expand the health
insurance coverage to uninsured groups, control costs, enhance quality, and
expand access to care. Preventive services will be assigned to the medical care
system, while new roles and responsibilities will be defined for public health
agencies. The clinical preventive services likely required are examined in a
population of 44,565 persons residing in Otsego County, New York. Expansion of
preventive services to Medicaid requests and the uninsured will require
considerable resource expenditure to correct the current deficit in preventive
services received by these groups. Moreover, the uninsured and Medicaid
recipients have high levels of risk behaviors, identifying a need for health
education services effective to that population subgroup. The transfer of
responsibilities for clinical preventive services to the medical care system may
free up resources for public health agencies to focus on other initiatives such
as disease surveillance, health education, and quality assurance. New
interrelationships, some cooperative and some adversarial, are likely to emerge,
due to a closer working relationship between the medical care system and public
health agencies than previously seen in American health care.
PMID- 10186588
TI - New Jersey health promotion and disease prevention initiative.
AB - Health promotion is a major component of the rhetoric about health care reform at
a national level. However, it is likely that the benefit packages included in any
congressional legislation will be limited and unsatisfactory, thus compelling the
states to take the lead. New Jersey is the first state to enact a comprehensive
health promotion and disease prevention law; this legislation has the potential
to change medical practice in the state.
PMID- 10186589
TI - School-based health centers and managed care health plans: partners in primary
care.
AB - School-based clinics provide important access to health care for adolescents. For
the past 20 years in St. Paul, Minnesota, Health Start has been a nonprofit
organization providing comprehensive primary care services in the city's public
high schools. Over the past decade, Minnesota has seen the growth of managed care
plans for both the private and public (Medicaid) sectors. For the past several
years, Health Start has been building relationships with managed care plans in
order to coordinate care for adolescents. Since managed care plans differ in
their management, reimbursement, and service delivery methods, Health Start has
developed several models of partnership with managed care plans for the delivery
of primary care to adolescents enrolled in school.
PMID- 10186590
TI - Six principles of public health information.
AB - The collection and analysis of data has been a fundamental activity of public
health since the earliest times. Automated systems have enabled public health
agencies to accumulate vast amounts of data. This data becomes useless without a
systematic approach to convert it into information that directs action. Public
health systems that manage service delivery should be integrated to maximize
efficiency and minimize burdens upon program staff.
PMID- 10186591
TI - CDC's Information Network for Public Health Officials (INPHO): a framework for
integrated public health information and practice.
AB - To strengthen the public health infrastructure, the Centers for Disease Control
and Prevention (CDC) initiated the Information Network for Public Health
Officials (INPHO). CDC INPHO has three goals: (1) to make communication among
public health practitioners throughout the United States easy, (2) to make
information accessible, and (3) to make secure data exchange as swift and smooth
as contemporary technology will allow. Based on a systems approach to supporting
the core functions of public health, CDC INPHO achieves its goals by creating a
flexible and user-responsive infrastructure of open communications and
information exchange.
PMID- 10186592
TI - Developing an integrated public health information system for Missouri.
AB - The Missouri Department of Health realized it had a problem with 67 different
information systems that ran on different platforms and could not communicate
with one another. A new, integrated information system, the Missouri Health
Strategic Architectures and Information Cooperative (MOHSAIC) is being developed
based on information engineering (IE). This article describes IE, the process of
developing MOHSAIC, and some key lessons learned in developing the system. Some
of the lessons learned include the importance of executive sponsorship, tension
between efficiency and program accountability, importance of confidentiality, and
difficulties of funding an integrated system. The article stresses how integrated
information systems will be important for the viability of public health under
health care reform.
PMID- 10186593
TI - Public health issues in the development of centralized health care databases.
AB - The establishment of centralized databases, in conjunction with health care
reform, offers us an opportunity to enhance the collection of data supportive of
public health functions. However, this opportunity may be lost without the
informed, persuasive, and persistent participation of the public health community
in the database development process. Maryland's effort to construct a statewide
database illustrates the political forces and technical complexity involved in
the task. It also demonstrates how public health officials, by making their views
known, can influence database design and health care reform.
PMID- 10186594
TI - Validation of a screening survey to assess local public health performance.
AB - The study seeks to validate an abbreviated protocol for measuring local public
health performance. Primary data were collected during 1993 on a series of
indicators keyed to defined public health core functions and their associated
practices. The data were obtained from responses provided by local health
department directors and were reviewed for accuracy by respective state health
department personnel. All local public health jurisdictions (370) in six states
were surveyed with a screening protocol. A sample of 36 of these jurisdictions
was then resurveyed by means of a full-length protocol using 84 different
indicators of public health performance. Correlations between scores obtained
from the screening survey and those from the reference survey were high for
overall public health performance, for each of the three functions, and for some
of the ten practices. A group of only four queries was shown to predict reliably
the overall scores. Findings support the conclusion that public health practice
can be defined, measured, and monitored. A proposed surveillance system is
feasible.
PMID- 10186595
TI - The impact of Medicaid managed care on the public health system in Arizona: case
study.
AB - This article examines the impact of a statewide Medicaid managed care program,
the Arizona Health Care Cost Containment System (AHCCCS), on the local public
health system in Arizona. Based on interviews with current and former state and
local public health officials, the authors describe public health concerns with
capitated health care delivery systems that rely on gatekeeper systems to control
utilization. The authors identified difficulties in gauging the extent of the
problem, since neither public health nor managed care systems collect data on use
of public health clinics by AHCCCS beneficiaries. Relationships between public
health officials and managed care officials are characterized by tensions
resulting from differing outlooks about access, eligibility, and the need for
preventive health services. The report concludes with recommendations developed
by the Association of State and Territorial Health Officials (ASTHO) Primary Care
Committee on roles for state health agencies in ensuring development of
appropriate managed care delivery systems for vulnerable populations.
PMID- 10186596
TI - The potential impact of health care reform on public health HIV-related
activities.
AB - This article observes that, despite the clear potential benefits of health care
reform's expanding health insurance coverage for people with human
immunodeficiency virus (HIV) disease, there is a real danger of losing existing
acquired immunodeficiency syndrome (AIDS) services if federal categorical public
health programs are cut. It discusses the considerable accomplishments of the
Ryan White CARE Act and of Centers for Disease Control and Prevention (CDC)
prevention funding. The funding for these current efforts will not be assumed by
near universal insurance coverage for a variety of reasons, including the need to
care for populations who are neglected by health care reform, to continue
services unlikely to be reimbursable, and to offer care in a range of locations
other than licensed health care facilities.
PMID- 10186597
TI - Maternal and child health and health care reform.
AB - Women and children, because of particular characteristics and vulnerabilities,
should be afforded special attention in health care reform. Health care reform
provides an opportunity to positively affect the maternal and child health (MCH)
status. Universal coverage of a comprehensive benefit package must be combined
with a strong public health system of population-based services if benefits are
to be realized. There must be an accountable public locus of responsibility for
promoting MCH, including clear authority and resources for four primary
activities: (1) core public health, (2) systems development, (3) coordinated
services for children with special health care needs, and (4) access to care.
PMID- 10186598
TI - Dental public health strategies and health care reform.
AB - There are significant challenges that need to be met to improve oral health in
this country. Even if access to clinical preventive dental services is increased
through a national health care plan, substantial improvement in the country's
oral health cannot be achieved without support and assistance of public health
initiatives. In January 1993, the steering committee for the Core Functions
Project, U.S. Public Health Service, issued a report, Health Care Reform and
Public Health: Population-Based Core Functions, to address the health care needs
and conditions of populations as opposed to the individual health care needs
under consideration by the national health care reform initiative. By adapting
the report's core functions to the public's oral health, this article lays a
foundation for the prevention, protection, and promotion of America's oral
health.
PMID- 10186599
TI - Evaluating prevention and quality of care in managed care plans: a public health
perspective.
AB - Public health practitioners are challenged to ensure the continued provision of
necessary services in a rapidly changing delivery system. To accomplish this, new
approaches to evaluating access and quality on a population basis are needed.
This article presents a number of possible methods for evaluation, with
particular emphasis on strategies related to managed care in Medicaid. The
importance of considering cost containment in evaluating access and quality and
in changing systems is discussed.
PMID- 10186600
TI - Linkages between academics and practice leadership development in public health.
PMID- 10186601
TI - Public health assessment in a new context.
PMID- 10186602
TI - Public health assessment in the 1990s.
PMID- 10186603
TI - What is assessment?
AB - The Institute of Medicine's report on The Future of Public Health identified
assessment, policy development, and assurance as core functions of public health.
Assessment is a process whereby public health agencies identify health problems,
identify health resources and evaluate their effectiveness, and present the
results of these analyses to decision makers. These efforts are carried out
through a division of labor among local, state, and federal agencies. The
responsibility for assessment extends to all areas of the country and to every
area of public health: from infectious diseases to chronic conditions, from
behavioral risks to environmental hazards, and from motor vehicles to hand guns.
PMID- 10186604
TI - A cooperative effort to pass tobacco control ordinances in Wichita, Kansas.
AB - In October 1993, the Tobacco-Free Wichita Coalition proposed ordinances to the
Wichita City Council that would tightly control access of minors to tobacco and
prohibit smoking in public places. The subsequent successful change in local
health policy required the collaborative efforts of local and state organizations
and health agencies. A simple random telephone survey commissioned and financed
by the coalition demonstrated that 76 percent (95 percent CI = 72 percent to 80
percent) of adult Wichita-Sedgwick County residents favored enforced penalties
for merchants selling tobacco to minors, and 62 percent (95 percent CI = 58
percent to 66 percent) favored a ban on tobacco vending machines. Fifty-four
percent (95 percent CI = 50 percent to 58 percent) favored a smoking ban in all
public places.
PMID- 10186605
TI - Tobacco, alcohol, and other drug use behaviors among adolescents in Erie County,
New York.
AB - This article provides estimates of the prevalence of tobacco, alcohol, and other
drug use behaviors of ninth-grade students enrolled in public and parochial
schools in Erie County, New York. A computer-scannable survey consisting of 50
questions was completed by 7,891 students in the fall of 1992. Survey findings
show that tobacco and alcohol are the drugs used most often by ninth-grade
students. Results also indicate that cigarette use is strongly associated with
other drug use behaviors such as getting drunk, using marijuana, and other
illegal drugs. A report detailing findings from the survey has been widely
disseminated to school officials and community leaders throughout Erie County.
Our experience in conducting this survey suggests that collecting information on
the drug use behaviors of adolescents at the local level is both feasible and
worthwhile.
PMID- 10186606
TI - Improving Medicaid pediatric care.
AB - This article uses Medicaid claims data to examine the adequacy of well-child care
provided by different ambulatory care providers for selected children enrolled in
Maryland Medicaid. Considerable provider variation was observed. The majority of
the nearly one-quarter of the children with no well-child visits during the year
appeared to have had no regular primary care source. Results contributed to the
development of a managed care program designed to increase care accessibility and
continuity and improve provider practices. Advantages and disadvantages of using
claims data to investigate this public health issue care discussed.
PMID- 10186607
TI - The Georgia Information Network for Public Health Officials (INPHO): a
demonstration of the CDC INPHO concept.
AB - The Georgia Division of Public Health is serving as the first demonstration model
of a statewide implementation of the Centers for Disease Control and Prevention
Information Network for Public Health Officials. The goals of the project are to
make communication easy, to make information accessible, and to make data
exchange as swift and as smooth as technology will allow. By having a state-of
the-art telecommunications network, public health officials will be able to
rapidly collect health data and transform them into meaningful health status
information that can be used to inform health policy decisions. The Georgia
Information Network for Public Health Officials is a unique consortium of private
and public sector partners funded with a grant from the Robert W. Woodruff
Foundation. The project will install the telecommunications infrastructure and
the supporting software to position Georgia public health as the health
information leader of the state.
PMID- 10186608
TI - Public health practice and public health education: a personal view of their
current relationship.
AB - In its 1988 report, The Future of Public Health, the Institute of Medicine stated
that schools of public health had become "somewhat isolated" for public health
practice. Since then a great deal has been done to address this issue by the
academic community, state and local public health practice agencies, foundations,
and federal health agencies. This commentary reviews their most important actions
and identifies some unresolved issues.
PMID- 10186609
TI - Emerging pathogens--the white horse of the apocalypse?
AB - The concept of emerging microbial disease is discussed both in a historical and
contemporary perspective. Major factors contributing to emergence of viral,
bacterial, rickettsial, and parasitic diseases over the last 25 years are
discussed. Forty agents are listed in a table by year of recognition/emergence,
mode of transmission, geographical distribution, and symptom complex. Public
health prevention and control measures and long-term public health implications
are also summarized. Suggestions are offered on how to retrieve appropriate
information on newly emerging pathogens and to obtain authoritative and timely
information on surveillance data using electronic mail access.
PMID- 10186610
TI - Managing change in the era of health reform: organized delivery systems of public
health.
AB - As U.S. Medicaid managed care programs proliferate, it appears that traditional
clinical training and practice often provide insufficient preparation for
physicians to meet the care requirements of Medicaid beneficiaries adequately.
State and local health departments have extensive experience with this
population's need for preventive care, social support services, care
coordination, and referral. Organized delivery systems of managed care can merge
the expertise of primary care practitioners, public health professionals, and
other community resources to deliver comprehensive care. Although the described
model includes Medicaid as the payer, it would remain viable should Medicaid be
terminated and universal coverage enacted.
PMID- 10186611
TI - Enhancing student practicum opportunities: the outbreak investigation option.
AB - An outbreak investigation practicum option for graduate students at the
University of Washington School of Public Health and Community Medicine has three
goals of education, scientific investigation, and exposure to operations of
public health agencies. Over a six-year period, 48 students performed 40 outbreak
investigations in collaboration with adjunct faculty based in local public health
agencies. An outbreak investigation practicum at Yale University had similar
goals, but the rapid-response team approach there generally involved one regular
faculty member and a team of graduate students. In either program, the level of
faculty involvement necessary for outbreak investigations is sustainable only if
the faculty value public health practice as part of the school's mission. Since
public health students need to acquire many practical skills, a short outbreak
investigation practicum experience should not be viewed in isolation, but rather
should be one of a variety of practicum offerings available to students at
schools of public health.
PMID- 10186612
TI - Immunization outreach at Income Support Centers, New York City, 1992-1993.
AB - An increase in measles occurred in New York City (NYC) during 1989-1990,
affecting primarily unvaccinated preschool-aged children. Many of these children
were also enrolled in Aid to Families with Dependent Children (AFDC) programs. To
determine the immunization status of children receiving AFDC, immunization
records were reviewed at three NYC income support centers. Records were assessed
for vaccination eligibility on the day of the visit and at various ages. Seventy
six percent of the children were found eligible for vaccination on the day of
their visit. Vaccination levels at two years of age were among the lowest
measured in New York. Future immunization efforts should be directed toward this
population.
PMID- 10186613
TI - Outcome-based management and public health: the Oregon Benchmarks experience.
AB - Oregon is taking major steps toward monitoring health and nonhealth issues
through the use of an outcome-based management approach called Benchmarks.
Developed through a lengthy statewide consensus-building process, there are
currently 272 goals, or Benchmarks, for the years 1995, 2000, and 2010, of which
54 are health related. Major effects on both the state and the local health
departments include enhanced assessment activities, increased health planning,
and improved collaboration both among health agencies and with other governmental
and nongovernmental organizations.
PMID- 10186614
TI - Ten academic barriers to public health practice.
PMID- 10186615
TI - Doing the impossible.
PMID- 10186616
TI - New horizons for public health nursing.
PMID- 10186617
TI - Public health nursing within core public health functions: "back to the future".
AB - This article defines the role of public health nursing within the core public
health functions and health care reform. It discusses the process used in
Washington State to define the core public health functions and the development
of the Public Health Improvement Plan. It further articulates how the core
functions work was built upon to develop a futuristic public health nursing model
that incorporates population-based services. The article concludes by discussing
some of the challenges and barriers to implementation of the model, yet assuring
that public health nursing has a role in public health practice well into the
21st century.
PMID- 10186618
TI - Exploring ethical terrain in public health.
AB - Public health is rife with ethical challenges. Ethical principles and values are
intrinsic to public health decision making, although they are generally not
identified explicitly. One purpose of this article is to discuss public health
goals as an ethical/value concern with attention to values that do and should
underlie health care in the United States. A second purpose is to introduce
frameworks for public health decision making that incorporate ethical
considerations into community and health promotion perspectives of public health
decision makers. Public health policy makers and providers are urged to explore
ethical/value dimensions of the health care system and to use the ethical
frameworks in their decision making, expanding the more individualistic
perspective of traditional bioethics.
PMID- 10186619
TI - Follow the money: funding streams and public health nursing.
AB - The increasing reliance of health departments on income generated by billing for
individual clinical services impacts the role and outlook of public health
nurses. This commentary discusses some of the reasons for the emergency of that
finance trend and the current shifts in financing personal care, with
observations on the challenges facing nurses in public health agencies today.
PMID- 10186620
TI - Building a new health system: implications for public health management and
practice.
AB - Changes in the health care system should encourage private-sector health care
providers and the public health system to work in partnership to improve the
public health of all citizens. Minnesota, with its recent comprehensive health
reform efforts, has made a strong commitment to strengthen the public health
system in performing those functions that are critical to protecting the health
of the public and meeting public health goals that are identified by the state
and local communities.
PMID- 10186621
TI - The development of a consumer guide on the quality of obstetrical services: the
Missouri experience.
AB - Missouri published a consumer guide on obstetric in the spring of 1994. This
article describes the events and processes that led to the publication of the
guide. The guide provided obstetrical quality-of-care indicators on structure,
process, and outcomes for each facility doing deliveries. The article describes
the principles followed in developing the guide, how the indicators were chosen,
how the guide was constructed, and what data sources were used. Several lessons
were learned including: a guide opens communication within the provider
community, development of a guide is a long process, an advisory committee and
preliminary review of findings by providers are necessary, and strong technical
expertise is essential.
PMID- 10186622
TI - Performance-based public health in Texas.
AB - Responding to a 1987 state audit report, the Texas Department of Health began a
performance-based objectives project to tie contract funds to local health
departments (LHDs) to performance measures. The overall goal of the project is to
improve public health practice in Texas. A major focus has been on having
regional and LHD program staff develop realistic and measurable outcome and
process objectives. Training on the planning and monitoring phases of the health
program management cycle has been conducted, with future training planned on the
evaluation phase. There are increasing reports on the value of the performance
based objectives process.
PMID- 10186623
TI - Capacity-building influences on Illinois local health departments.
AB - Illinois local health departments (LHDs) were surveyed in 1992 and again in 1994
in order to assess changes in, influences on, and results of practice performance
during this two-year period. Illinois LHDs serving both small and large
populations were found to have greatly increased the extent to which they carry
out practice measures related to public health's core functions. The Assessment
Protocol for Excellence in Public Health (APEXPH) and its Illinois adaptation
were cited as the most positive influences on practice performance. LHDs viewed
the most significant consequences of participation in needs assessment and
planning processes as increased understanding of internal strengths and
weaknesses and of community health problems. These findings and implications
suggest that significant improvements in LHD practice performance can result from
widespread implementation of APEXPH and its derivatives.
PMID- 10186624
TI - Cancer data profiles for local cancer prevention and control initiatives.
AB - Four state health agency interventions to extend a state data-based planning
model to regional areas via development of regional cancer profiles are analyzed.
The content of and the process used to develop profiles in each state are
characterized in terms of the objectives, target audience, cancer sites
addressed, level and type of data presented, plan for profile evaluation as well
as factors that influenced these characteristics and common challenges.
Consistency is observed across states in profile characteristics, in the factors
influencing these characteristics, and in implementation challenges.
PMID- 10186625
TI - Community-based breast health partnerships.
AB - Breast Health Partnerships are a unique community-based method for delivering
comprehensive breast cancer screening services. They are problem-solving groups
that work to bring the resources of individual partners "to the table" to
overcome obstacles to the recruitment of underserved women and the delivery of
comprehensive breast cancer screening services. Partners include representatives
from government agencies as well as the voluntary and private sectors. Developing
this "community of solution" increases institutionalization of key components of
a comprehensive screening program. Simultaneously, it increases fiscal
accountability by ensuring local resources are maximized before public dollars
are spent.
PMID- 10186626
TI - On publishing in an agency setting.
AB - Writing journal articles quite often becomes a low priority for public health
professionals in a busy agency setting. Despite the obstacles, an agency setting
offers many opportunities to enhance public health knowledge. Opportunities for
publication in an agency setting are reviewed, with examples of citations from
the published literature.
PMID- 10186627
TI - Guidelines for the practice of public health.
AB - Guidelines based on the best science and expert opinion, widely disseminated to
our state and local public health departments, private health care providers, and
policy makers, will enhance our public health efforts. Communities will finally
have information to guide them in developing population-based programs that have
proven to be effective, both from the standpoints of health status and cost. The
effort described in this article is to test the feasibility of public health
practice guidelines.
PMID- 10186628
TI - Academic public health and managed care.
AB - Health care delivery is going through revolutionary changes. There is a shift
toward providing care under the auspices of managed care organizations (MCOs).
These MCOs are becoming larger and more comprehensive while increasingly focused
on preventive and public health issues. Quality of care, health economics, health
services research, data and information systems, quantitative analysis, and the
social and behavioral sciences are all becoming important areas of expertise for
MCOs and are vital to their successful operation. Thus schools of public health
can contribute considerably to MCOs by making their curricula relevant to a
managed care environment and having faculty members and research programs that
recognize the public health overlap with managed care.
PMID- 10186629
TI - An academic linchpin.
PMID- 10186630
TI - The great powers.
PMID- 10186631
TI - Put prevention into practice: a systematic approach.
AB - Use of a systematic program, such as Put Prevention Into Practice (PPIP), to
improve the delivery of clinical preventive services by public health nurses is
recommended. The Public Health Service, a part of the U.S. Department of Health
and Human Services, designed PPIP to help achieve the goals of Healthy People
2000. PPIP is a research-based team approach using a kit of materials targeted at
patients, providers, and the office/clinic system. It includes pocket-sized
patient booklets, a Clinician's Handbook of Clinical Preventive Services, posters
for the waiting and examination rooms, flowcharts and alert stickers for medical
records, prescription pads, and reminder postcards. Sources of the materials,
implementation and evaluation strategies, and groups implementing the program are
discussed.
PMID- 10186632
TI - Directly observed therapy: the medicine works.
PMID- 10186633
TI - Creation of a tuberculosis directly observed therapy provider network in New York
City: a new model of public health.
AB - A 1990-1991 New York State Department of Health (NYSDOH) assessment of the
ongoing tuberculosis (TB) epidemic in New York City (NYC) led to legislative
enactment of policy recommendations to help stem the epidemic. The principal
strategy entailed mobilization of community resources for TB directly observed
therapy (DOT) to supplement the DOT available from the NYC Department of Health
(NYCDOH). For implementation, the NYSDOH engaged a coalition of public and
private health care providers in a TB DOT Provider Network. Network participants
include freestanding facilities, many of which already have preexisting
affiliative relationships through which DOT can be extended. The number of
individuals receiving DOT in NYC has increased more than 10-fold in two years.
Over 1,000 individuals have completed their anti-TB treatment while enrolled in
the network.
PMID- 10186635
TI - Communicating the public health message.
PMID- 10186634
TI - A new approach to public health practice experiences.
PMID- 10186636
TI - Selective directly observed therapy: appraisement and perception of likely
participants.
AB - Directly observed therapy (DOT) has become a popular strategy in tuberculosis
(TB) control. Limited resources to provide DOT makes selection of patients an
issue. Studies were done in San Francisco to analyze the socioeconomic and
behavioral characteristics of 1992 TB patients--and of those on DOT--and to
determine attitudes of indigent San Franciscans toward TB and adherence to TB
control measures. The studies show that (1) African American and Latino patients
were more likely to be selected for DOT than Asian/Pacific Islanders and whites,
regardless of factors associated with adherence behavior, and (2) DOT, delivered
in a respectful manner and combined with incentives, was evaluated positively by
those with risk factors.
PMID- 10186637
TI - Hospital care of tuberculosis patients referred for directly observed therapy in
New York City: identifying factors in prolonged stays.
AB - Individuals hospitalized and treated for tuberculosis (TB) who were then enrolled
into TB directly observed therapy at four study hospitals in New York City (NYC)
were identified. Review of hospital medical records determined whether the
hospitalizations were warranted and whether lengths of stay were prolonged. Most
hospitalizations were appropriate but over 70 percent of cases analyzed had
prolonged stays. Of these, almost half were to document bacteriologic response to
anti-TB treatment. Some were prolonged due to misunderstanding of state
recommendations. Focused educational efforts could significantly reduce lengths
of stay and save up to $9.7 million annually in NYC hospitalization costs.
PMID- 10186638
TI - Public health campaign funds provide a "safety net" for indigent tuberculosis
patients at the Mount Sinai Hospital.
AB - This article describes the development of a partnership between a voluntary
health care institution and a state agency for a focused public health program
providing vital clinical, public health, and social supportive services. In
addition to the historical development of this alliance, the article illustrates
joint problem-solving processes to address complex issues. Since its inception in
1992, this collaboration has resulted in significant improvements in the health
status of a high-risk, difficult-to-serve, indigent population that would
otherwise pose a public health threat to the community. Demographics of 17
indigent patients are described. Nine have completed treatment for tuberculosis
under directly observed therapy and completion is in sight for six others. None
have been lost to follow-up.
PMID- 10186639
TI - Implementing a directly observed therapy program in an urban community hospital.
AB - St. Clare's Health and Hospital Center has implemented a directly observed
therapy (DOT) program for a challenging urban population of largely HIV+ patients
in response to a need for the prevention of the spread of multidrug-resistant
tuberculosis in the population. Identified treatment barriers are needs of
patient subgroups within the population. Issues in the implementation include:
patient compliance, effectiveness of patient identification and follow-up, and
continuity of care. Challenges to continuity of care include patients signing out
of the hospital against medical advice and missed clinic appointments. Patient
identification and follow-up is enhanced by coordinating DOT treatment with the
methadone maintenance treatment program.
PMID- 10186640
TI - Tuberculosis treatment through directly observed therapy in a large multisite
methadone maintenance treatment program: addressing the public health needs of a
high-risk population.
AB - The rate of tuberculosis in patients receiving methadone treatment is
significantly greater than the general population. The stabilization of former
injection drug users occurs within methadone maintenance treatment programs,
indicating the suitability of these sites for directly observed therapy (DOT).
There are formidable barriers to the success of DOT, some are institutional,
others patient-related. Strategies to address these obstacles need to be
implemented. The integration of DOT into existing programs required support from
the New York State Department of Health, institutional commitment, as well as
continued staff and patient education and training.
PMID- 10186641
TI - The Harlem family model: a unique approach to the treatment of tuberculosis.
AB - With the increased incidence of tuberculosis and especially of resistant cases in
the United States, directly observed therapy as a mechanism for ensuring
completion of therapy has been advocated. This mechanism has been primarily
pioneered and utilized in developing countries. Few models have been tailored to
specific patient populations in this country. At Harlem Hospital, in recognition
of the special needs and characteristics of our patients with tuberculosis, we
have developed a unique program. This program revolves around a family model with
all components of the program contributing to the cohesiveness of all the program
participants and staff. In the brief period since its inception, the program has
been successful in enrolling and retaining a large number of patients with
tuberculosis.
PMID- 10186642
TI - Tuberculosis, HIV disease, and directly observed therapy.
AB - Directly observed therapy (DOT) to enable completion of antituberculous therapy
works. DOT is largely responsible for the recent improvement in tuberculosis case
rates in New York City. Despite this favorable trend, the factors of significant
HIV disease rates and of multidrug resistant forms of tuberculosis bacteria in
the population are of grave concern. Therefore, in addition to DOT other means of
preventing tuberculosis spread should be encouraged. These include directly
observed preventive therapy (DOPT) programs, use of masks, improved ventilation
in crowded settings such as homeless shelters, and ultraviolet light germicidal
irradiation of upper room air in such locations.
PMID- 10186643
TI - The development of integrated public health information systems: a statement by
the Joint Council of Governmental Public Health Agencies.
AB - To truly enjoy the benefits of the information age, public health agencies at
each level of government must work together to plan and implement integrated
information systems that meet the needs of our dynamic profession. The Joint
Council of Governmental Public Health Agencies, comprised of state and local
health officials, has worked to identify the solutions to public health's
information needs. Investments in integrated systems that support service
delivery to clients will improve program management and enhance accountability
for public funds. The ability to produce good, client-centered data will be
essential as the nation's health and welfare systems change.
PMID- 10186644
TI - Taking training seriously: a policy statement on public health training by the
Joint Council of Governmental Public Health Agencies.
AB - Continuing education and on-the-job training in public health has suffered
serious neglect over the past years. As a result, many state and local public
health entities have failed to keep step with emerging challenges facing the
public's health--challenges that require new and innovative approaches to
prevention and treatment. In this article, the Joint Council of Governmental
Public Health Agencies seeks to affirm the importance of public health training
by examining barriers to training; identifying areas in which training should be
emphasized; providing examples of successful training programs; and recommending
ways in which public health leaders can revitalize training programs.
PMID- 10186645
TI - A simple methodology to finance public health initiatives: reimbursement for
tuberculosis directly observed therapy services in New York State.
AB - New York State (NYS) used Medicaid reimbursement to create incentives for health
care providers to offer directly observed therapy (DOT) services for active
tuberculosis (TB) disease. This resulted in proliferation of 26 new TB DOT
providers and expanded capacity for the New York City (NYC). Department of
Health. As a result, over 1,200 individuals now receive DOT in NYC. The
reimbursement methodology was also used for other NYS public health initiatives.
It is applicable for public health initiatives elsewhere.
PMID- 10186646
TI - Evaluating local public health performance at a community level on a statewide
basis.
AB - As part of efforts to develop a surveillance system to evaluate local public
health performance, six state health departments surveyed local health
departments in their states. Overall, 370 respondents (94 percent) returned
completed surveys. Based on responses to 26 indicators, the mean percent
community performance of the three core functions of public health was 56 percent
of the potential score. Scores were also calculated for perceived adequacy of
performance and for each of 10 practices linked to the three core functions.
Variations in performance were related to population size, state, and
administrative relationship of local jurisdictions to the state. These results
suggest local public health performance can be evaluated at a community level on
a statewide basis using a relatively small number of indicators.
PMID- 10186647
TI - Beyond informatics: an electronic community infrastructure for public health.
AB - Public health agencies are in the early stages of building an electronic
infrastructure that will link them to each other and eventually to the
"information superhighway." Emphasis in planning and development is on data
systems and the information and training services that can enhance essential
public health services. This article argues for a larger vision of the potential
of electronic networks for public health. It discusses the health and other
challenges facing public health, the limitations of conventional efforts, and the
emerging consensus on public health core functions. Finally, it examines current
and potential uses of information technology. The article concludes by proposing
that the public health community should develop a collaborative and inclusive
vision of public health in an electronic world and provide guidance and support
for agency implementation to ensure a stronger system that can meet the health
and health equity challenges ahead.
PMID- 10186648
TI - Herbicide regulation: a case study of Michigan.
AB - Lawn-care herbicides are a type of pesticide regulated under federal and state
pesticide legislation. The Michigan Department of Agriculture implements
herbicide regulation to protect the public's health and welfare. Yet, due to gaps
that exist in all levels of government in the regulation of lawn-care herbicide
application, the public is placed at risk. The federal pesticide legislation
(Federal Insecticide, Fungicide, and Rodenticide Act) provides for a lower
standard of safety in the classification of herbicides applied in the residential
context as opposed to the agricultural context. Michigan legislation (The
Pesticide Control Act) exempts from the law persons applying general herbicides
on their own premises. The state does not require public notification of risks or
safety precautions prior to commercial application of these herbicides.
Furthermore, on-site inspections are not performed for residential application of
herbicides and the state applicator certification program is not assessed for
effectiveness.
PMID- 10186649
TI - Public health in private practice: the challenge of immunizing preschool
children.
PMID- 10186650
TI - Prospects for childhood immunization registries in public health assessment and
assurance: initial observations from the All Kids Count initiative projects.
AB - This article offers an overview of selected evaluation findings from the initial
implementation year of the Robert Wood Johnson Foundation's All Kids Count
childhood immunization initiative in which demonstration projects were funded to
develop community-based immunization registry and follow-up systems in 14 sites
throughout the United States. The basic components of these systems, the process
through which these registries were developed, efforts to secure the
participation of private sector providers, the prospects for system success at
the community level, and the potential for these immunization programs to
influence other aspects of primary health care for children are addressed.
PMID- 10186651
TI - The Vaccines For Children program: issues of physician accountability and patient
verification.
AB - To address the issue of low immunization rates, President Clinton in 1993
introduced the Child Immunization Initiative (CII). One part of the CII is the
Vaccines for Children (VFC) program, a federally-funded and state-operated
vaccine supply program. Recently, congress has raised concerns regarding the
extent to which noneligible children may be receiving VFC vaccine. This article
explores, from several perspectives, the major issues related to VFC
accountability. The two major accountability systems under consideration,
benchmarking and vaccine replacement, are reviewed and analyzed for their
potential accuracy, their effects on physician office practice, and their impact
on the entire VFC program.
PMID- 10186652
TI - Missed opportunities for immunizations: a review of the evidence.
AB - Employing a literature review approach, this article explores the evidence about
missed opportunities for childhood immunizations, their impact on immunization
rates, and potential solutions. It concludes that missed opportunities contribute
significantly to the underimmunization of children. A concerted effort to reduce
missed opportunities, particularly those that are relatively easy to eliminate,
could yield measurable improvements in immunization levels of children. Missed
opportunities for vaccinations have been found to occur in virtually all primary
care settings, and their impact is greater for populations having low baseline
immunization rates. Coverage levels could be improved by up to 30% in many
settings by eliminating missed opportunities. Major reasons for missed
opportunities include providers lacking knowledge about immunization status,
provider or practice policies resulting in failure to vaccinate, and
inappropriate contraindications. Solutions include promulgation and acceptance of
useful guidelines for delivery of immunizations, provider and patient education,
assessment and feedback about a practice's missed opportunities, and modification
of routine practice styles within primary care and other health care settings.
PMID- 10186653
TI - The impact of WIC and AFDC in screening and delivering childhood immunizations.
AB - Two publicly funded programs, the Special Supplemental Food Program for Women,
Infants and Children (WIC) and Aid to Families with Dependent Children (AFDC),
serve large numbers of children who may be at risk for poor immunization status.
A review of the literature as well as conference abstracts and program reports
for studies of immunization initiatives carried out in these settings was
conducted. Although the available literature is limited, it does indicate that
children in these programs have low immunization levels and that interventions to
improve their immunization status can be successful. Measures to improve
immunization status should be implemented through WIC and AFDC.
PMID- 10186654
TI - Assessment and related immunization issues in the Special Supplemental Nutrition
Program for Women, Infants and Children: a status report.
AB - This article reports the results of a survey undertaken to determine the current
level of collaboration between Women, Infants and Children (WIC) programs and
immunization services. While the results of this study are encouraging, WIC needs
to continue to place emphasis on using written or computerized immunization
records for client screening, utilize available computer hardware and software to
assist assessments, and expand the use of food voucher incentives as a strategy
to improve coverage.
PMID- 10186655
TI - Information as intervention: how Georgia used vaccination coverage data to double
public sector vaccination coverage in seven years.
AB - All states are now required by federal law to measure immunization coverage in
each public clinic in their jurisdiction once a year. This law is based on data
suggesting a twofold increase of immunization coverage in public clinics in
Georgia during a seven-year period when the state developed a system for
measuring clinic coverage and using these data to stimulate immunization
performance. Review of the history of the development of the Georgia system
suggests that measurement alone is not sufficient to raise coverage, however. In
Georgia, measurement was coupled with a vigorous program of feedback of coverage
data, provision of incentives for good performance, and exchange of information
among clinics. The Centers for Disease Control and Prevention (CDC) has
summarized the Georgia system with the acronym AFIX--Assessment, Feedback,
Incentives, eXchange of information--and recommends that all state immunization
program managers test and adapt this methodology. The article comments on the
development of the Georgia system and describes why CDC believes other states
should adopt it.
PMID- 10186656
TI - Potentials for improving health department immunization rates: the relationships
between service delivery factors and immunization completion.
AB - The majority of children at risk for incomplete immunizations receive care in the
public sector. A multivariate model of differing health department practices and
policies was developed to assess their association with immunization completion
rates among health department users in Georgia's 159 county health departments.
Simulations based on the model tested the impact of several programmatic and
policy options. Higher immunization rates were associated with no fees, more
clinical sites, computerized tracking systems, fewer missed opportunities,
younger age of initial immunizations, and greater per capita budgets. A
combination of these health department factors could increase immunization rates
by 18 percent.
PMID- 10186657
TI - Medicaid managed care in New York: problems and promise for childhood
immunizations.
AB - New York State is aggressively pursuing mandatory Medicaid managed care. Under
managed care, physicians and plans have a defined population for which they are
responsible, quality assurance monitoring emphasizes immunization rates along
with other preventive services, and population-based incentives are possible. The
literature does not offer compelling evidence, however, that immunization
coverage is any better in managed care than under fee-for-service. If
reimbursement is low and physician capacity insufficient, immunization rates may
be considerably worse. In New York, care needs to be taken so that expansion does
not outstrip the capacity of managed care plans to absorb additional enrollees.
PMID- 10186658
TI - Public health reform.
AB - Changes in funding and social and public policy will compel public health
departments to reexamine their structure and values. Along with a reduction in
providing health care services, public health will see a renewed emphasis on
primary prevention. At the heart of primary prevention are marketing,
communication, and community organizing. Unfortunately, these disciplines are all
too often considered beyond the scope of public health and are contracted out or
ignored. The commentary calls for a revitalized role for public health based on
organizational adjustments consistent with anticipated changes in social policy
and health care delivery.
PMID- 10186659
TI - Cornerstone: Illinois' approach to service integration.
AB - Cornerstone is a management information system developed and implemented by the
Illinois Department of Public Health as a mechanism to facilitate maternal and
child health service integration. Its design features combined program
registration, standardized risk assessment, automated care plan development, and
consolidated referral and scheduling. Cornerstone is a flexible, PC- and local
area network-based system, allowing portability across program applications and
geographic areas. A wide-area network enables local agencies to share data about
clients. Development of Cornerstone was a collaborative effort by potential
Cornerstone users and statewide administrative staff. The standard for equipment
is set at a one-to-one ratio of workstations to case managers.
PMID- 10186660
TI - Immunizations: the promise and the pitfalls.
AB - Despite our success with eradicating smallpox and possibly poliomyelitis, the
United States faces unacceptably low immunization levels among preschool-age
children. The problems associated with ensuring complete protection of children
from vaccine-preventable diseases are multifaceted. Many children remain at risk
for potentially fatal diseases, and the easy transmissibility of these agents
increases the threat of disease outbreaks. This commentary examines steps needed
to improve immunization levels and pediatric primary care, access.
PMID- 10186661
TI - Public health practice coordinators.
PMID- 10186662
TI - A brief history and inventory of immunizations.
AB - This article attempts to summarize succinctly the origins, past history, present
armamentarium, and possible future directions of immunizing agents. Individual
discoveries and governmental initiatives have led to large-scale immunization
programs that have proven the success of this primary preventive tool. Examples
of missed opportunities have been noted. Like previous vaccines, the newer
vaccines will require scientific proof of efficacy and public acceptance. Unlike
other primary preventive tools (chlorination of water, pasteurization of milk),
future successful immunization programs will require active participation, of the
public and continuous governmental education in order to protect its citizens.
PMID- 10186663
TI - State and federal partnerships for the application of cancer control science.
PMID- 10186664
TI - Cancer prevention and control: a science-based public health agenda.
AB - A public health agenda for cancer prevention and control is presented that is
based upon scientific evidence from epidemiologic studies. This agenda gives
priority to primary prevention focused upon tobacco, diet, sexual activity,
alcohol, sunlight, and physical activity. In addition, secondary prevention or
screening is discussed, comparing ACS guidelines and NCI statements. The
immediate task for public health is to develop cancer prevention programs that
will eliminate the disparity in cancer morbidity and mortality across racial and
ethnic groups and reduce risk in all segments of the population.
PMID- 10186665
TI - Public health approaches to tobacco use prevention and cessation in the U.S.
AB - Tobacco has a long history of use in the U.S., and its serious health effects
have been well-documented during the past half century, U.S. efforts to control
tobacco use and tobacco-related morbidity and mortality have been reasonably
successful over the past 25 years, during which time there has been a 34 percent
reduction in adult smoking. Nevertheless, tobacco use remains a significant
public health problem in the U.S., with more than 430,000 tobacco-related deaths
per year and over one-fourth of the population continuing to smoke. Many
organizations are involved in tobacco use control activities, the most broadly
focused of which is the National Cancer Institute (NCI). As an example of the
type of program needed to address the problem of tobacco use on a national scale,
the NCI's public health research plan and activities are described and its
emphasis on a data-based decision matrix in its approach to tobacco and cancer
control research and applications of research is discussed. Finally, future
approaches to tobacco use control in the U.S. are suggested.
PMID- 10186666
TI - The national 5 A Day for Better Health Program: a large-scale nutrition
intervention.
AB - As cancer gains on heart disease as the leading cause of death, there is
increased urgency to improve the current diet that contributes to 35 percent of
cancer deaths. Lacking have been consensus about the strength of the science
base, political will, resources, and conceptualization about what can be done in
communities to change dietary behaviors. Over the past 10 years, the 5 A Day for
Better Health Program has emerged as the major population-based initiative for
nutrition and cancer prevention. The 5 A Day Program is a national theory-based
program that approaches Americans with a simple, positive message: eat five or
more servings of fruit and vegetables daily as part of a low-fat, high-fiber
diet. This article describes the elements and theories woven into the national 5
A Day Program, provides a description of the important components of the program,
and outlines the issues that will face dietary change initiatives in the future.
PMID- 10186667
TI - The National Breast and Cervical Cancer Early Detection Program: a comprehensive
public health response to two major health issues for women.
AB - The passage of the Breast and Cervical Cancer Mortality Prevention Act
established a nationwide, comprehensive public health program to increase access
to breast and cervical cancer screening services for women who are medically
underserved. This act created the first opportunity for state health agencies to
build a public health infrastructure for cancer control at the state and
community levels. The Congress appropriated $30 million in fiscal year 1991 for
the first year of this program. In the summer of 1991, the Centers for Disease
Control and Prevention (CDC) used a competitive application process to fund the
first eight states to establish early detection programs. Since then, the
National Breast and Cervical Cancer Early Detection Program (NBCCEDP) has become
a nationwide program with a budget of $100 million. Thirty-five states and nine
American Indian Tribes are supported to implement comprehensive screening
programs. Fifteen states, three territories, and the District of Columbia receive
planning and infrastructure grants as part of the Capacity Building Program. The
NBCCEDP surveillance data through January 31, 1995 shows that 556,003 screening
tests have been provided to women who are medically underserved. The success of
NBCCEDP has contributed to the growing pressure on state health agencies to focus
more attention and resources on chronic disease prevention and control.
PMID- 10186668
TI - Development of cancer prevention and control initiatives in a state health
agency: the New York experience.
AB - The public health response to cancer in the New York State Department of Health
has evolved over many years. A number of organizational units contribute to
surveillance and monitoring, quality assurance, policy analysis and advocacy,
education, service delivery, and evaluation components. Extensive cooperation
with health professionals and consumers outside of state government is also
essential.
PMID- 10186669
TI - Progress in breast cancer screening: Vermont's efforts.
AB - To impact Vermont's high breast cancer death rate, a statewide survey was
conducted to identify barriers to screening. An awareness campaign was
implemented that included community meetings, worksite education, television and
radio ads, and physician education. A follow-up survey showed a significant
increase in women ever having a mammogram and a significant decrease in women who
felt that mammograms were not needed, the greatest identified barrier to
screening. Despite increased awareness of breast cancer nationwide, it is likely
that the education strategy successfully targeted and impacted women's behavior.
Continued educational efforts are needed, particularly in women 50 and older.
PMID- 10186670
TI - State legislation related to breast cancer: 1980-1994.
AB - Increased screening mammography usage is important for reducing breast cancer
mortality in the United States. This article summarizes state breast cancer
screening legislation enacted between 1980-1994. Forty-three laws were identified
and analyzed based on five categories: screening/education programs; third-party
reimbursement for screening; third-party reimbursement for
reconstruction/prosthesis; mammography facility accreditation; and alternative
therapy information. Third-party reimbursement mandates were subdivided into
Medicaid/public assistance; state employee health benefits; Medicare supplement
insurance; age/frequency provisions; and screening based on risk factors besides
age. The larger context of breast cancer screening needs for the present and
future are discussed.
PMID- 10186671
TI - The future of cancer control research and translation.
AB - The future holds great promise for translating advances in cancer control
research to populations at risk-much is known about how to prevent cancer. Within
the Institute of Medicines overall framework of assessment, policy development,
and assurance, this article summarizes 10 cancer control priorities. Important
themes include evaluation, cost-effectiveness analysis, shrinking the "latency
period" between elucidation of preventive technologies and widespread
application, coalition building, and development of adequate cancer control
resources. Despite increased cancer control efforts among public health agencies
over the past decade, little measurable progress has been made in reducing
overall cancer mortality. A renewed commitment to controlling cancer is needed
from health policy makers and even the public health community.
PMID- 10186672
TI - Building an infrastructure for data-based cancer control planning and
intervention implementation.
AB - Health agencies have traditionally played a central role in the characterization
of health problems and disease. Data-based planning is considered the cornerstone
of effective public health action, enabling state health agencies to use limited
resources most effectively to achieve maximum reductions in disease morbidity and
mortality. Over the past decade, state health agencies have made important
strides in enhancing their capacity for data-based planning for cancer control
and in establishing models to facilitate similar planning efforts in other
states. Federal programs have served an important catalyst role in establishing
states' data-based planning capacity and in facilitating the resulting increase
in the application of cancer control science across the United States. This
article provides an overview of the infrastructure for data-based cancer control
planning and highlights the critical role of federal programs in enhancing the
capacity of states to effectively plan and implement cancer control initiatives
as well as some of the gaps that remain in states' capacity for data-based
planning.
PMID- 10186673
TI - Managed care: public health opportunity.
PMID- 10186674
TI - Year one of HIV prevention community planning: a national perspective on
accomplishments, challenges, and future directions.
AB - Two of the most important principles for the implementation of successful human
immunodeficiency virus (HIV) prevention programs are the following: (a) planning
for the programs must be done in conjunction with members of affected
communities; and (b) the foundation of the programs should consist of solid
behavioral, social, and epidemiological science. In 1994, the Centers for Disease
Control and Prevention and its prevention partners formally implemented HIV
prevention community planning in order to address these two key factors. The
occasion of the one year anniversary of HIV prevention community planning is
marked by taking stock of progress-to-date from a national perspective. This
article reviews year one accomplishments and difficulties, and describes the
trajectory of HIV prevention community planning for year two and beyond.
PMID- 10186675
TI - CDC and ATSDR electronic information resources for health officers.
AB - This article catalogues some of the Centers for Disease Control and Prevention's
(CDC) more important information resource offerings, which make public health
information accessible via computer and automated telephone systems and on
electronic media (diskette and CD-ROM). We review mechanisms for: (1) finding and
retrieving CDC reports, (2) querying CDC's numeric data files, (3) transmitting
surveillance and other data files to CDC, (4) exchanging electronic mail with CDC
staff, and (5) disseminating state and local public health information and data
using CDC tools. Each resource is followed with a section on how to obtain access
to these resources.
PMID- 10186676
TI - Chronic disease mortality in Maine: assessing the targets for prevention.
AB - From 1982 through 1991, nine chronic diseases accounted for over 55 percent of
deaths in Maine. Using the lowest age-specific death rates as theoretically
achievable rates, there were over 8,000 excess deaths. Over 25,000 deaths could
be attributed to preventable causes over the 10-year period. Cigarette smoking
was the single largest contributor to chronic disease mortality, accounting for
17,688 deaths, followed by physical inactivity, high blood pressure, and diet.
This assessment provides a measure of the size of the chronic disease prevention
target in Maine and is a first step in assessing the potential impact of
prevention programs.
PMID- 10186677
TI - School-based tuberculosis testing and treatment program: comparing directly
observed preventive therapy with traditional preventive therapy.
AB - A high-school-based health center instituted a tuberculosis testing and treatment
program. Compliance of purified protein derivative (PPD) positive students with
isonicotine hydrazine (INH) preventive therapy was compared for two groups of
students: those in directly observed preventive therapy (DOPT) and those in
traditional therapy. Four hundred thirty six students were tested and 429
returned for a reading: 209 (49 percent) students had a positive PPD test. The
rate of positivity did not vary by age, sex, or years in the United States. There
was no relationship between bacille Calmette-Guerin (BCG) vaccination and rate of
positivity or mean size of induration. The compliance rate for all courses of
DOPT was significantly higher (54 percent) than that for traditional therapy (26
percent). The compliance rates for the first and second attempts to complete a
course of DOPT was 71 percent. Completion of therapy did not differ by age, sex,
or years in the United States. Haitian students completed therapy more often than
students from Jamaica. We believe it is effective and efficient to base
tuberculosis testing and treatment with DOPT in the school setting.
PMID- 10186678
TI - Is public health ready for reform? The case for accrediting local health
departments.
AB - Reform of the governmental public health system in the United States has been
stymied by changes in political, economic, and medical care landscapes since
public health was called to action by the Institute of Medicine report in 1988.
Despite a new national health objective calling for 90 percent of the population
to be served by a local health department effectively addressing public health's
three core functions by the year 2000, capacity building initiatives have not
been deployed extensively, and there is little likelihood of reaching the year
2000 objective. A national program of accrediting local and state health
departments could energize public health capacity building. Accreditation would
build on recent initiatives in states like Washington and Illinois, promote wider
use of the Assessment Protocol for Excellence in Public Health, and facilitate
reform of the public health system around public health's core functions. Key
questions addressing the why, how, and who of such an initiative set the stage
for consideration of a national accreditation program.
PMID- 10186679
TI - A tripartite regulation of health networks.
AB - With the Republicans in power, market-driven forces of managed care plans,
capitated payment, and the regional networks (alliances) are likely to serve as
centerpieces for improving the organization, financing, and delivery of our
nation's health services. These "voluntary" alliances of health providers and
health insurance underwriters foreshadow the powerful, geographically linked
regional health networks that are now becoming oligopolies. As a result of these
providers developing monopolistic practices, state health services commissions
will be formed to regulate market share, the scope of health services,
reimbursement rates, and profits. State departments of public health will
continue to focus on broader community health initiatives such as access and
quality. Complexities of relationships among those regulated by these responsible
agencies, and the interfacing of these state health services commissions and
state departments of public health and insurance, with their potentially
conflicting goals and political forces, are expected.
PMID- 10186680
TI - Implementation issues and costs associated with a proven strategy for increasing
breast and cervical cancer screening among low-income women.
AB - Results from a randomized controlled trial demonstrated that a physician reminder
letter combined with telephone counseling from a health educator significantly
increased women's use of both mammograms and Pap tests in a low-income population
in a managed care setting. This article presents results from a process
evaluation and cost analysis of the intervention. An average of 35 minutes was
spent preparing each of 304 intervention letters for mailing, including the time
needed to secure signatures from 110 physicians. The results of an economic
analysis suggested that this intervention cost $11.44 per recipient and $28.93
per screening test received above expected. However, intervention costs can be
reduced significantly if one physician signs all letters (rather than each
woman's own primary care physician) and if the health educator labor costs are
diminished (e.g., by using student interns). Overall, the women under study
reported that they are comfortable with both mailed and telephone reminders when
they are post due for a clinical preventive service.
PMID- 10186681
TI - Working with community health advisors as part of the community health team.
AB - Community health advisors as part of the community health team offer new avenues
for reaching client populations, but also present unique challenges.
Administrative lessons learned from the implementation experience of the
Sisters/Companeras Project are presented.
PMID- 10186682
TI - Multicultural maternal and child health outreach: Washington State strategies to
assure access for Asian and Pacific Islander women and children.
AB - This article outlines some of the barriers to health care experienced by Asian
and Pacific Islander Communities. The authors then describe a number of
strategies the Washington State Department of Health has used to reduce cultural
and linguistic barriers to health care. As a state health agency, the Department
has promoted accessible programs through mechanisms such as improved data
collection, culturally competent staff, targeted outreach, and development of
partnerships with community organizations and other agencies to promote
culturally accessible health care delivery.
PMID- 10186683
TI - Strengthening public health practice content in public health training.
AB - U.S. schools of public health have recognized the imperative to strengthen the
public health practice content of training for future public health
practitioners. Five strategies to develop administrative and curriculum programs
within schools of public health to address this need are described: (1)
institution of centers for public health program evaluation; (2) creation of
automated field placement and apprenticeship programs; (3) formalization of
linkages with professional management training programs to create a track for
future senior managers of community health agencies; (4) establishment of cross
departmental applied public health faculty tracks; and (5) offering applied
public health evaluation scholarships for students. These initiatives may provide
incentives for the institution of a public health practice focus within schools
of public health.
PMID- 10186684
TI - Medicaid managed care and public health policy.
AB - This article provides an overview of managed care concepts and highlights several
issues for public health practitioners. Taken from a transcription, this summary
is based on a Forum on Public Health and Health Reform held in Atlanta, Georgia,
on May 12, 1995, sponsored by the Public Health Practice Program Office, Centers
for Disease Control and Prevention. Examples of issues related to managed care
for public health practitioners discussed here include: (1) building on managed
care plan report cards for large employers so they have an expanded community
perspective; (2) developing report cards for Medicaid managed care plans; (3)
obtaining patient encounter information from managed care plans for purposes of
surveillance and epidemiologic studies; (4) adjusting provider utilization
profiles to take into account the differences in the population being served; (5)
linking managed care plans with specialized public health providers and community
institutions; and (6) consumer surveys related to prevention and public health
services.
PMID- 10186685
TI - Recognizing and supporting the role of public health surveillance: intensive care
for a core public health function.
PMID- 10186686
TI - The future of national public health surveillance in the United States.
AB - Public health surveillance systems should have the capacity to collect and
analyze data, disseminate data to public health programs, and regularly evaluate
the effectiveness of the use of disseminated data. Unfortunately, in the United
States, systems of public health surveillance are fragmented and do not
adequately address either current or new potential challenges to public health.
This commentary addresses components of any effort toward a national public
health surveillance system and highlights examples of these components in state
and national surveillance developments.
PMID- 10186687
TI - Impediments to public health surveillance in the 1990s: the lack of resources and
the need for priorities.
AB - With the increased demand for public health surveillance data comes the
development of new surveillance systems and the expansion of existing systems. A
corresponding increase in financial and personnel resources to support data
collection, particularly at the local public health department level, has been
documented. Adequate and timely surveillance data are critical to both overall
public health program design and evaluation and to meet emerging surveillance
needs. Without an emphasis placed on priorities and resources for public health
surveillance, the foundation upon which public health decisions are based is
threatened.
PMID- 10186688
TI - Blueprint for a national public health surveillance system for the 21st century.
AB - This article lays out a blueprint for public health surveillance and assessment
for the year 2000 and beyond. The blueprint defines the roles of local, state,
and national public health agencies and partners in the medical care system in
conducting surveillance and assessment activities. It proposes a new over-arching
National Public Health Surveillance System to be the conceptual framework for all
public health surveillance and assessment activities into the 21st century.
PMID- 10186689
TI - Integrating public health information and surveillance systems.
AB - The Centers for Disease Control and Prevention (CDC) recognizes sound public
health information is the essential ingredient of all of its work and the key to
effective public health decision making. A CDC/ATSDR committee reached a
consensus that CDC needed to streamline and consolidate its public health
surveillance and information systems into an integrated system. With integrated
systems, a wide range of diverse individual information systems will continue to
exist but these systems must be coordinated, interconnected, comparable, and easy
to use. The "glue" that holds these systems together consists of (1) uniform data
standards, (2) communications networks, and (3) policy-level agreements regarding
data access, sharing, and reduction of data collection burdens. By putting the
appropriate policy-making apparatus and resources in place, CDC believes the end
result will be a streamlined process that meets the information needs of CDC and
its partners with less confusion and frustration.
PMID- 10186690
TI - Laboratory reporting and disease surveillance.
AB - Disease surveillance is an important tool which is used to identify diseases that
are hazardous to public health. Historically, surveillance systems were created
to capture physician reports of notifiable diseases. However, state evaluations
of surveillance systems found inadequacies with systems based solely on physician
reporting. To improve these systems, most state health departments have required
reports of laboratory tests used to diagnose notifiable diseases. This article
has a brief summary of the benefits and limitations of laboratory reporting.
PMID- 10186691
TI - Overcoming barriers and reaping the benefits of surveillance for infectious
diseases: the New Mexico perspective.
AB - Surveillance for disease is one of the cornerstones of public health practice in
the United States. Surveillance, particularly for infectious diseases, has
allowed the detection of outbreaks and provided for the long-term monitoring of
disease incidence. In New Mexico, acquired immunodeficiency syndrome (AIDS)
surveillance is characterized as one of the most comprehensive surveillance
systems for an infectious disease to be found anywhere. The success of this
system is largely a result of state and federal resources and a good partnership
with the AIDS/human immunodeficiency virus health care providers. Surveillance
for Haemophilus influenzae type b (Hib) has demonstrated a remarkable decline in
disease incidence in the state especially since the use of second generation Hib
capsular polysaccharide conjugate vaccine. In contrast, surveillance for
hepatitis A has demonstrated a significant public health problem that is largely
not being addressed by current control measures.
PMID- 10186692
TI - Improving the reporting of notifiable diseases in Texas: suggestions from an Ad
Hoc Committee of providers.
AB - In an effort to increase passive surveillance in Texas, an ad hoc committee of
private and public health providers met to suggest changes in the list of
reportable diseases and ways to improve provider participation. This group noted
several reasons to make changes in the list of reportable diseases. Deletion was
suggested for diseases whose reports did not warrant action from public health
authorities or for previously common diseases, which were now rare and occurred
as isolated events. Reasons to add a disease were recognition of new conditions
of public health importance or the observation that a previously rare disease was
now becoming common. It was the group's consensus that diseases reportable by law
need to reflect realistic public health responses.
PMID- 10186693
TI - History and current status of the National Notifiable Diseases Surveillance
System.
AB - The National Notifiable Diseases Surveillance System (NNDSS) has origins dating
more than a century ago and continues to serve today as a timely source of
national data. Both the history and the current status of the NNDSS illustrate
the collaborative effort required among persons at all levels of the medical and
public health systems. The evolution of the list of conditions considered
nationally notifiable demonstrates the responsiveness of the system to changing
priorities. The NNDSS has also evolved with the development of technology; it
currently uses computers for the collection of data rather than letters or
telegrams. These fundamental factors--partnerships, shifting priorities, and
rapidly changing technology--will continue to characterize and to influence the
practice of public health surveillance as it evolves during the 21st century.
PMID- 10186694
TI - Learning to design new systems: communicable disease surveillance.
AB - The basis for public health actions and its supporting information systems are
being questioned. Problems with the New Jersey communicable disease surveillance
system were examined. Inability to discriminate unusual disease patterns was
disclosed. In addition, there was prolonged processing time, high costs, and lack
of capability to identify emerging infections. A new approach for communicable
disease surveillance using a hospital laboratory isolate-based reports is
described. The project could have been completed faster and with less expense if
the project could have benefited from other recent management experience dealing
with similar problems.
PMID- 10186695
TI - Improving and integrating data systems for public health surveillance.
AB - The National Center for Health Statistics (NCHS) is the nation's principal health
statistics agency, with a primary mission to collect, disseminate, and analyze
health data. NCHS has a clear commitment to a wide range of improvements in
surveillance and public health information systems. Building on its long history
of conducting multipurpose surveys where the needs and interests of a variety of
programmatic interests have to be accommodated, NCHS is working on a number of
fronts to improve and better integrate data systems so that they will be more
useful for public health surveillance. Examples include the redesign of the
National Health Interview Survey, the integration of the Department of Health and
Human Services' health surveys, the retooling of the vital statistics system, and
the movement to subnational data collection.
PMID- 10186696
TI - Environmental public health surveillance.
AB - A holistic and collaborative approach needs to be taken in the development of
environmental public health surveillance systems. Exposure and hazard
surveillance integrated with outcome-based surveillance will blend fragmented
strands of data into streams of information. Adequate resources and strong
leadership are essential to the creation of such surveillance systems.
PMID- 10186697
TI - Surveillance and the National Center for Prevention Services.
AB - Five key surveillance issues faced by the National Center for Prevention Services
for the next 10 years are: 1) developing surveillance for risk factors, 2)
agreeing on and standardizing definitions, 3) integrating surveillance systems
into general public health information systems, 4) integrating surveillance and
public health information systems into patient care data systems, and 5)
integrating health service and programmatic data into surveillance and public
health information systems. Current technology and public health needs combine to
make development of integrated, compatible surveillance and information systems
essential, not just desirable.
PMID- 10186698
TI - Future issues in HIV/AIDS surveillance.
AB - Public health surveillance for human immunodeficiency virus (HIV) seeks to define
and quantity the spectrum of HIV risk, infection, and disease at the local,
state, and national levels. Reporting of cases of acquired immunodeficiency
syndrome (AIDS) or HIV and seroepidemiologic surveys are the primary methods. In
selected areas, this infrastructure supports supplemental systems that address
issues of risk or infection beyond the scope of routine surveillance. Future
concerns include maintaining the basic HIV/AIDS surveillance infrastructure,
maintaining flexibility to meet emerging needs, improving surveillance for
incident infections and risk behaviors, and enhancing the capacity of community
based groups to use surveillance data in setting priorities for prevention and
care.
PMID- 10186699
TI - Information and surveillance systems and community health: building the public
health information infrastructure.
AB - The scope and purpose of public health injury and disease surveillance systems
will expand in response to the increasing information needs of communities and
health organizations. Public health leaders must focus on the entire information
infrastructure. Surveillance and information systems need to evolve to include
targeting and evaluating community-wide prevention programs. Standards governing
exchange as well as data content will become central to these new systems and the
emerging health information infrastructure. Future surveillance systems will face
challenges in forming partnerships with managed care organizations, in developing
new information tools, and in training the public health workforce.
PMID- 10186700
TI - Underreporting of Lyme disease by Connecticut physicians, 1992.
AB - To determine the magnitude of underreporting of Lyme disease, a random sample of
Connecticut physicians was surveyed in 1993. The magnitude of underreporting was
assessed by comparing physician estimates of Lyme disease diagnoses with reports
of Lyme disease sent by physicians to the Connecticut Lyme disease surveillance
system. Complete questionnaires were returned by 59 percent (412/698) of those
surveyed. Of the 224 respondents who indicated that they had made a diagnosis of
Lyme disease in 1992, only 56 (25 percent) reported a case of Lyme disease that
year. Survey results suggested that, at best, only 16 percent of Lyme disease
cases were reported in 1992. Physician underreporting of Lyme disease
underestimates the public health impact of Lyme disease.
PMID- 10186701
TI - Optimizing professional education in public health.
AB - Traditional public health education has lacked required practicums such as are
the rule in other health professions. Described is a model professional education
program that is built around required course work in all areas of public health
and a series of mandatory internships at sites of public health practice,
utilizing state and local health departments, other federal and state agencies,
and public and private sites where students are supervised in public health
rotations similar to those a medical, dental, nursing, or veterinary student
would experience in a clinic or ward.
PMID- 10186702
TI - Social marketing/health communications: leadership opportunities for the 1990s.
PMID- 10186703
TI - Forcing the task.
AB - Although not generally included in public health curricula, public health policy
formulation is essential to local agency public health operations. When public
health measures are mandated by referendum of the electorate, such as the HIV
exposure notification laws passed in California in 1988, health agencies must act
prudently and quickly to formulate effective policies. We found it prudent to
convene a task force that brought together the critical, albeit diverse,
legal/judicial/health players. This action not only served to bring about
consensus, but provided us with an opportunity to educate participants about the
policy, and the implementation of appropriate communicable disease measures.
Through consensus and education, we were able to implement the disclosure laws in
a timely manner, create an atmosphere of trust, and enable a skilled and
confident workforce.
PMID- 10186704
TI - Motor vehicle crashes are a leading cause of injury-related death.
PMID- 10186705
TI - Public health and environmental protection: where will the leadership be?
PMID- 10186706
TI - Time to address infant mortality.
PMID- 10186707
TI - The environmental Web: a national profile of the state infrastructure for
environmental health and protection.
AB - The success of our national environmental policies depends upon the capacity of
states to implement them. This article presents the findings of an examination of
the state level organization of environmental health and protection services. The
goals of the project were to conduct a descriptive analysis of the structure,
functions, and funding of state environmental health and protection services, and
to examine the impact of the major federal environmental statutes on the
organization of the state infrastructure. Future environmental progress will
depend upon an improved understanding of the relationship between human health
and the environment. This will require a commitment to improving the public
health training of environmental professionals, and improved cooperation between
health and environmental agencies to assure that they do not lose sight of their
fundamental mission--the protection of public health.
PMID- 10186708
TI - Social support and adverse pregnancy outcome in a high-risk population.
AB - Low birth weight is a significant health problem in the United States,
particularly among poor women. By combining traditional predictors of birth
weight with social support indicators, we were able to substantially improve the
discrimination between the highest birth weight quartile from the lowest among
high-risk gravidae receiving first time prenatal care at the Albany, New York,
County Department of Health. The impact of traditional predictors and social
support indicators varied considerably between African-American and white women.
Providers of care to poor women can utilize this information to maximize the
likelihood of a good birth outcome.
PMID- 10186709
TI - Linking high-risk, low-income, pregnant women to public health services.
AB - Utilization of public health services by high-risk pregnant women is contingent
on women's awareness of those services. This article reports on an evaluation of
public health promotional methods and compares high-risk pregnant women users of
public health services to eligible nonusers. For women who used public health
services, the two most frequently reported sources of information were a public
health nurse or a friend. Users of services in contrast with nonusers tended to
have had fewer pregnancies, lower income, and use WIC. They were also less likely
to attend church and to have more contact with their child's school. These
findings can assist agencies in planning outreach activities.
PMID- 10186710
TI - A cost evaluation of implementing a quality-oriented, regional perinatal data
system.
AB - We evaluated the cost impact of implementing a perinatal data system (PDS) on
birth certificate (BC) processing and perinatal quality improvement (QI)
reporting. Relevant staff in all birthing hospitals in the 15-county Central New
York region (N = 23) were interviewed at baseline prior to implementation of the
PDS and one year after implementation of the PDS to ascertain the time and costs
of BC processing and of QI report generation. The average time and cost to
collect and complete BCs did not change significantly from baseline to year 1.
The time and costs to complete QI reports decreased significantly by 70 percent
during this same period. Hospitals fully using the PDS for QI reporting purposes
took, on average, six percent of the time it took other hospitals to generate
comparable QI reports. The PDS significantly reduced the time and cost of
generating perinatal reports from a consolidated database over what hospitals had
done previously. Given the richness of the reports and the efficiency with which
they are produced, hospitals are encouraged to adopt electronic means of BC
processing and accessing these data for QI reporting purposes.
PMID- 10186711
TI - Racial variations in cesarean section rates: an analysis of Medicaid data in
Louisiana.
AB - The objective of this study was to investigate racial variation in cesarean
section rates among Medicaid beneficiaries in Louisiana. Results indicate that
over a three-year period, white women had higher rates than women of other races
when stratified by age, locality, accompanying diagnoses, and hospital ownership.
Comparing Louisiana Medicaid data with birth certificate records, rates among all
births were slightly higher than Medicaid births, with the same racial trend.
These variations imply significant differences in costs and reimbursement to
providers and raising questions about efficiency of current obstetric practices
in Louisiana. Implications for a managed care system are discussed.
PMID- 10186713
TI - Sexually transmitted disease control in the era of managed care: "magic bullet"
or "shadow on the land"?
AB - Sexually transmitted diseases (STDs) are a major public health problem. In the
United States, nearly 12 million STD infections occur annually, generating
estimated direct annual health care costs exceeding $12 billion. Lifetime costs
may total $88 billion. Meanwhile, inflation-adjusted public funding for STD
clinical care and control decreased over the past two decades. Previous STD
control officials warned that declining support for STD control programs would
result in program elimination and increased rates of STDs ("Brown's Law").
Effective public health and primary prevention efforts have been difficult to
implement because of societal sensitivities about sexuality, and the curative
rather than preventive focus of our health care system. Proven cost-effective
medical interventions, such as chlamydia screening, have not been universally
implemented because of health care system inefficiencies, whereby public STD
clinical services generate private sector savings not reinvested into these
public prevention programs. However, the dramatic growth in managed care presents
opportunities, as well as risks, for better STD management.
PMID- 10186712
TI - Future trends affecting public health: challenges and opportunities.
AB - Many accomplishments of public health can be cited, yet public health
professionals face unprecedented challenges and opportunities in the coming
decades. To assist public health practitioners, researchers, and educators in
preparing for current and future changes affecting the population's health, the
authors describe several important "macrolevel" trends. These trends include: the
aging of the population, changing patterns in the U.S. racial/ethnic composition,
changes in health care delivery systems, the explosion of information
technologies, changing needs in the public health work force, the growth in
health-related partnerships, and anti-government sentiment and polarization. A
series of implications for each of the major trends is provided. It may be
important for public health leaders and policy makers to take these trends and
implications into account as they plan and prioritize future approaches to
disease prevention and health promotion.
PMID- 10186714
TI - Cardiovascular disease control efforts among local health departments in
Missouri: four-year trends and policy implications.
AB - Knowledge, attitudes, and activities in cardiovascular disease (CVD) control
among local health departments in Missouri were surveyed in 1990 and in 1994,
following four years of a community-based CVD risk-reduction project.
Hypertension screening was rated as the most frequently performed CVD-related
activity in 1990 and in 1994. Differences in mean scores between baseline and
follow-up surveys showed no significant changes except for cholesterol screening.
Respondents preferred individual patient education rather than community-wide
approaches to risk reduction. Our findings highlight the need for more emphasis
on coalition building and community-based programs for preventing and controlling
CVD at the local health department level.
PMID- 10186715
TI - Where do we go from here?
PMID- 10186716
TI - What do we pay for good health?
PMID- 10186717
TI - Good news and bad news for public health.
PMID- 10186718
TI - Public health expenditures: developing estimates for improved policy making.
AB - The Public Health Foundation (PHF), under contract to the U.S. Department of
Health and Human Services, Public Health Service (PHS), worked with federal,
state, and local public health, mental health, substance abuse, and environmental
agencies in nine states to develop and successfully test a methodology for
estimating investments in essential public health services. Estimates from the
nine-state sample revealed the predominance of personal health expenditures in
the public health system. Of total state health care dollars, only 1 percent was
spent on population-based health services by participating agencies. This pilot
provides a rational starting point toward a uniform methodology for highlighting
public health expenditures that may be critical in revealing the effects of a
changing health care environment on the nation's health. In combination with
other data, results are expected to lead to a more informed policy-making
process.
PMID- 10186719
TI - Assessing public health performance in Iowa's counties.
AB - Local health agencies in Iowa were surveyed to assess the performance of public
health practices in their communities. Responses were received from 97 percent of
counties. Less than 50 percent of counties were performing half of the indicators
of the Assessment function. Policy Development functions also were frequently not
performed. Performance was best in the Assurance function, with 86 percent of
counties reporting that they inform and educate the public. However, the other
three types of Assurance practices (Manage, Implement, and Evaluate) were
performed less frequently. Comparison of the performance of Iowa's rural counties
reveals a profile nearly identical to that reported elsewhere for a group of six
other states.
PMID- 10186720
TI - The challenge of developing community profiles for use in community health
assessment: lessons from Michigan's experience.
AB - In Michigan, a number of steps have been undertaken to revitalize a key public
health function--community health assessment. This article reports on the
activities of these initiatives, focusing on the beginning stage of the community
health assessment process--the development of community health profiles. The
findings and lessons learned from Michigan's experience, although state specific,
appear to have broad applicability to the entire local public health community.
It is hoped their publication will stimulate replication of this process among
this community in other states.
PMID- 10186721
TI - Public health practice linkages between schools of public health and state health
agencies: results from a three-year survey.
AB - Several recent examinations of the state of public health have called for
enhanced linkages between schools of public health and public health agencies,
prompting federal health agencies and schools of public health to develop
practice initiatives. Surveys of schools of public health and of state public
health agencies were conducted in 1992 to collect baseline data on practice links
between the two agencies; follow-up surveys were undertaken in 1993 and 1994.
Responses reveal that a substantial amount of interaction between schools and
agencies has been occurring for some time, but that until recently much of the
interaction has been informal and between individuals or departments rather than
institution-wide. Both frequency and formalization of such collaborations have
increased, reflecting a growing emphasis on public health practice activities at
schools of public health together with public health agencies.
PMID- 10186722
TI - Health care's double standard: the prevention dilemma.
AB - Curative services often have been judged by their perceived value, while
preventive services have been held to a more rigorous standard of documentation.
The dilemma for preventive services is not driven by evidence of their cost
ineffectiveness relative to curative services, but by the paucity of evidence of
any type. The issues are whether preventive services of different types are
perceived as having value, by what criteria these perceptions are measured, and
by whom they are determined. We examine five key constituencies, the measures by
which the value of prevention is judged, and the implications for the funding of
prevention activities.
PMID- 10186723
TI - Evaluation of a school-based sealant program in New York State.
AB - This study evaluated the outcome of a targeted dental sealant program by
comparing the survival probabilities of sealed high-risk first molar tooth sites
to unsealed low-risk tooth sites in 1,122 children enrolled in a school-based
sealant program. A comparison of the survival probabilities between low-risk
first molar teeth that did not receive sealants and the sealed high-risk first
molar teeth did not show significant differences. The results suggest that the
protocol used by the program provides a satisfactory method for identification of
children who could best benefit from sealants in a school-based situation.
PMID- 10186724
TI - Geographic issues in the analysis of a county-wide survey.
AB - Surveys are used by county public health departments to obtain data for purposes
such as risk factor inventories and program planning. Geographic data are often
collected from respondents in order to make sub-county estimates and to ensure
that the sample is representative of the population. This article addresses
geographic issues that arise in analyzing such surveys including: (1) the
assignment of respondents to geographic units, (2) the number of respondents
necessary per unit, (3) geographically appropriate questions, and (4) geographic
definitions. Data from a county-wide survey that highlight these issues are
presented and suggestions for improvements are made.
PMID- 10186725
TI - The presence of total quality management and continuous quality improvement
processes in California public health clinics.
AB - Total quality management (TQM) and continuous quality improvement (CQI) processes
have not been fully integrated into public health practice. Current levels of
participation and interest in TQM/CQI were assessed in California's 62 county
departments of health services. Survey results indicated that only 18.5 percent
of the 54 respondents were using TQM/CQI. Of those not using TQM/CQI, 75 percent
were interested in these activities. Improvement of public health clinic ability
to compete and to survive in a rapidly changing health care environment requires
fostering this interest through public health decision-maker support, increased
TQM/CQI training opportunities, and demonstration of TQM/CQI cost-effectiveness
in public health.
PMID- 10186726
TI - Mycotoxins and public health: a review.
AB - This article provides an overview of the public health implications of mycotoxins
-including a review of mycotoxin-related diseases documented in humans and
animals, recent associations between mycotoxin exposure and carcinogenicity, a
catalogue of foodstuffs documented to have been contaminated by mycotoxins, and a
description of the distribution of mycotoxins in both the United States and
worldwide. The article also advocates that public health professionals utilize
recent developments in the field of mycotoxicology to explore associations
between these fungal metabolites and acute and chronic disease in humans.
PMID- 10186727
TI - Teaching practice.
PMID- 10186728
TI - Prevention in the community: taking stock.
PMID- 10186729
TI - Defining characteristics of community-based health promotion programs.
AB - Community-based health promotion programs have flourished over the past twenty
years. These programs have varied considerably in their goals and in their
approaches to reaching these goals. While some flexibility is critical to program
effectiveness, it is also important to determine a set of defining
characteristics in order to distinguish community-based programs from other types
of health promotion activities. In this article, we examine some of the defining
characteristics of community-based health promotion programs, and the challenges
faced by practitioners who with to engage in this type of work.
PMID- 10186730
TI - Conducting a participatory community-based survey for a community health
intervention on Detroit's east side.
AB - This article describes a participatory action research process that brought
together community members, representatives from community-based organizations
and service providers, and academic researchers to collect, interpret, and apply
community information to address issues related to the health of women and
children in a geographically defined urban area. It describes the development and
administration of a community-based survey designed to inform an intervention
research project; discusses the establishment of a community/research partnership
and issues that the partnership confronted in the process of developing and
administering the survey; and examines the contributions of participants, and
implications for research and collective action.
PMID- 10186731
TI - Coalition building for prevention: lessons learned from the North Carolina
Community-Based Public Health Initiative.
AB - This article examines the four-year development of the North Carolina Community
Based Public Health Initiative consortium (NC CBPHI). The NC CBPHI consisted of
four separate county coalitions and differed in both its agenda and membership
from the many examples of coalitions described in the literature. This article
presents and describes evaluation findings that identify six factors as important
in coalition functioning and success in the CBPHI coalitions. These factors are:
participation, communication, governance and rules for operation, staff/coalition
member relationships, technical assistance and skills training, and conflict
recognition and containment. Selected CBPHI coalition activities are also
described and implications for public health practitioners are presented.
PMID- 10186732
TI - Principals and tools for evaluating community-based prevention and health
promotion programs.
AB - This article is an overview and practical guide for the evaluation of community
based disease prevention and health promotion programs. The article first offers
a rationale for evaluating community-based programs, then enumerates five
selected principles that are contemporary to community evaluation. The principles
are as follows: (1) evaluation of community programs should include an assessment
of program theory; (2) evaluation instruments that are used to measure community
programs must be contoured to each individual community; (3) evaluation
approaches used should be guided by the questions asked and often require both a
quantitative and qualitative orientation; (4) evaluation should be informed by
social ecology and social system concepts; and (5) community evaluation should
involve local stakeholders in meaningful ways. At the end of each principle, an
annotated reference list is provided that contains tools for applying the
principle to community evaluation.
PMID- 10186733
TI - Development of the Guide to Community Preventive Services: a U.S. Public Health
Service initiative.
AB - The Task Force on Community Preventive Services is developing a Guide to
Community Preventive Services (the Guide). Based on available evidence the Guide
will summarize the effectiveness and cost-effectiveness of population-based
interventions for prevention and control, and provide recommendations for people
who plan, fund, and implement population-based services and policies. On behalf
of the Department of Health and Human Services, the Centers for Disease Control
and Prevention is coordinating support to the Task Force from governmental
agencies, voluntary and professional groups, managed care organizations, and
academia to develop and implement the Guide. Publication is targeted for the year
2000. Individual components will be published when completed.
PMID- 10186734
TI - Improving community-based prevention by transforming managed care organizations
into health improvement organizations.
AB - Large nongovernmental health systems are taking over much of the direct delivery
of healthcare to populations previously served by health departments. This
article explores ways in which governmental and academic public health systems
can help maximize positive effects of this trend on community health. The
experience of Group Health Cooperative of Puget Sound is reviewed, with
particular attention to its prevention structure and work to address tobacco use.
An ideal preventive health improvement system model is presented, and future
directions and key lessons are explored.
PMID- 10186735
TI - Demonstration projects in community-based prevention.
AB - Community-based demonstration projects represent the translation of research
findings into practice. This article discusses the scientific basis for
demonstration projects and illustrates various principles through two large-scale
programs: the Health Promotion and Disease Prevention Research Centers and the
Community-Based Public Health initiative. These programs have shown several key
components for success, including: building effective partnerships, using
existing data effectively, adopting a causal model in intervention design,
employing appropriate evaluation techniques, using policy change as an
intervention, and utilizing the potential of community groups to foster change
among professional partners.
PMID- 10186736
TI - Reengineering public health: the two cultures revisited.
PMID- 10186737
TI - Bridging the gap between community-based prevention and managed care.
PMID- 10186738
TI - A model of the cost-effectiveness of directly observed therapy for treatment of
tuberculosis.
AB - A hypothetical cohort of 25,000 TB patients and their contacts were followed for
a 10-year period; rates of treatment default, infectiousness following partial
treatment, relapse, hospitalization, and development of drug-resistant TB were
included. The average cost per case cured was $16,846 with 15% of patients
starting DOT, $17,323 with 100% starting DOT, and $20,106 with none starting DOT.
The incremental cost per additional case cured was $24,064 when all patients,
started treatment on DOT, indicating that outpatient DOT provides a cost
effective method of improving health outcomes for TB patients and their contacts
while controlling direct costs.
PMID- 10186739
TI - Priorities and strategies for promoting community-based prevention policies.
AB - The public health community faces major choices in priorities for its mission in
a rapidly changing environment. One option is to place greater emphasis on public
health policy development. Policy making requires a grasp of the interplay among
stakeholders, policy makers, the press, and the public. A framework for gathering
relevant information and guiding strategic action is a useful tool for
participation in community, state, and national arenas in the interests of
population health. Organization-targeted approaches can make policy advocacy,
community mobilization, and public education about policy issues more effective.
This requires investment in public health infrastructure.
PMID- 10186740
TI - Predictors of mammography utilization in Missouri, 1993-1994.
AB - Mammography utilization data were studied for 915 women from a combined sample of
1994 Missouri Behavioral Risk Factor Surveillance System and a Special Breast and
Cervical Cancer Control Project Evaluation Survey, as well as similar data from
6,784 new participants in Missouri's Breast and Cervical Cancer Control Project
during 1993-1994. Among women aged 40 and over, having some college education and
having health insurance coverage were associated with a higher likelihood of ever
having a mammogram. Education, age, health care, Pap testing, and smoking were
identified as important predictors of compliance with recommended schedule of
yearly mammography among women aged 50 and over.
PMID- 10186741
TI - The Bridge to Health Project: a collaborative model for assessing the health of a
community.
AB - The Bridge to Health Project, a collaborative effort of 70 health related
organizations, was designed to collect population-based health status data about
approximately a half million residents in a primarily rural region in northeast
Minnesota and northwest Wisconsin. Funding and staff support were provided by a
regional medical center. The importance of sound survey methodology, role
clarification, adequate staff support, and a well organized process to foster
collaboration have applicability to other regions considering a collaborative
process of health status assessment.
PMID- 10186742
TI - Impact of a mandatory syphilis delivery test on reported cases of congenital
syphilis in Upstate New York.
AB - A regulation mandating a syphilis serology test at delivery was implemented on
December 6, 1989. To assess any impact on congenital syphilis reporting, we
compared all cases reported in Upstate New York for the year directly preceding
the regulation (n = 69) to those born in the three-year period following its
implementation (n = 239). After implementation, the percentage of cases not
tested at delivery decreased from 10 percent to 1 percent and reports of
syphilitic stillbirths tripled. Asymptomatic infection of both mothers and babies
increased significantly and at-birth detection of cases in women with negative
prenatal serologies increased by 43 percent. Delivery screening failed to
identify seven cases due to incubating maternal infection.
PMID- 10186744
TI - Asthma in Saudi Arabia: is the system appropriate for optimal primary care?
AB - The objective of the study was to assess the suitability of the structure of
Primary Health Care Centers to cater to the needs of patients with asthma.
Standards for optimal care were defined by the authors. The worst deficiencies
identified were in the availability peak flow meters, inhaler devices and
antiinflammatory drugs. Assessment of the optimal structure for asthma care was
found to demonstrate variance with national standards. More effort is recommended
in central development of guidelines. This assessment can be used to measure
future changes in asthma care.
PMID- 10186746
TI - Public access television: a grassroots approach to public health education.
PMID- 10186743
TI - Relationship of self-reported oral health and nutritional risk among hospitalized
older adults.
AB - Oral health and nutritional risk were assessed in 300 hospitalized older adults
using self-reported instruments. Patients who self-reported poor oral health
status were at greatest nutritional risk. Study results suggest that self
reported oral health and nutritional risk are multidimensional and that screening
instruments may help identify patients who could benefit from a dental referral.
The combination of nutritional and oral health screening methods may be an
efficient and cost-effective method for nondental health care providers to
identify and refer older adults for oral health care.
PMID- 10186745
TI - Investment opportunities and preventive intervention in for-profit HMOs.
PMID- 10186747
TI - Accrediting public health organizations: "the ducks is on the pond!".
PMID- 10186748
TI - Accrediting public health practice at the community level: issues, models, and
science.
PMID- 10186749
TI - The local public health agency review process in Oregon, 1985-1997.
PMID- 10186750
TI - Evaluating interventions for prevention and control of infectious diseases.
AB - This article describes approaches to evaluate interventions for prevention and
control of infectious diseases. Evaluation should take place at all stages in the
development and application of such interventions, whether preventive or
therapeutic. At least four different types of evaluation can be carried out:
developmental evaluation, relevance evaluation, process (administrative)
evaluation, and impact evaluation. For therapeutic interventions, cure is the
best indicator of effectiveness. For preventive interventions, reduction in the
occurrence of the condition is the best measure of effectiveness. However,
process and administrative evaluation and economic evaluation also play important
roles.
PMID- 10186751
TI - Changing promotion and tenure guidelines to include practice: one public health
school's experience.
PMID- 10186752
TI - Accreditation of public health practice in South Carolina, 1978-1997.
PMID- 10186753
TI - Accreditation of local public health practice in Illinois, 1993-1998.
PMID- 10186754
TI - Accreditation well-established in higher education; offers useful lessons for
other arenas.
PMID- 10186755
TI - Accreditation through Standards of Excellence for Public Health Organizations.
PMID- 10186756
TI - Joint Commission perspectives on accreditation of public health practice.
PMID- 10186757
TI - How accreditation could strengthen local public health: an examination of models
from managed care and insurance regulators.
PMID- 10186758
TI - Quality improvement, standards, and accreditation for community health services
in Australia, 1983-1995.
PMID- 10186759
TI - New directions for the national Community and Health Accreditation Standards
Program in Australia.
PMID- 10186760
TI - Performance measurement and accreditation of public health organizations: a call
to action.
PMID- 10186761
TI - Accrediting local health departments: potentials and pitfalls.
AB - A 1990 study was undertaken to determine if the public health infrastructure at
the community level could be used to evaluate a health department.
Characteristics of the infrastructure were defined and criteria were developed to
see if these characteristics would enable one to differentiate between health
departments. The appropriateness of a process of accreditation in carrying out
the assessment was also examined. The infrastructure concept had a validity,
utility, and composition that can be employed to make reasonable distinctions
between health departments. Further, use of an accreditation protocol to assess
the performance of local health agencies was found to be feasible.
PMID- 10186762
TI - Assessing the performance of local public health systems: a survey of state
health agency efforts.
AB - Throughout the past decade, growing attention has focused on ways to monitor the
performance of local public health organizations and ensure the adequacy of their
services. We surveyed representatives of the nation's state health agencies
during 1997 to examine their processes for local public health performance
assessment. Eighty-eight percent of agencies reported some involvement in
assessment activities. Of these agencies, 50 percent reported having an
assessment process that was currently operative. States reported using a
diversity of assessment methods. Results suggest that states are developing
performance assessment processes that are tailored to local resources, needs, and
priorities.
PMID- 10186763
TI - Organizational problems faced by the Missouri DOH in providing disaster relief
during the 1993 floods.
AB - This case study examines the organizational problems of Missouri Department of
Health (DOH) while providing flood relief in 1993. It reveals low awareness of
DOH's emergency plan, disorganized information collection, and perceptions that
federal flood relief was "resource-driven," not "need-driven." Lessons for other
health departments are (1) Information collection during disasters should be
centralized. (2) Health departments should train district offices to carry out
their emergency plan, and include local health departments in emergency planning.
(3) Federal and state agencies providing emergency aid should be sensitive to the
needs of district and local health departments.
PMID- 10186764
TI - A summary of efforts in Washington State to develop indicators for measuring the
performance of public health, 1994-1997.
PMID- 10186765
TI - The development of a comprehensive interdisciplinary HIV/AIDS center: a community
needs assessment.
AB - Meeting the needs of HIV-infected patients in a focused, cost-efficient,
coordinated manner is one of the most challenging problems in health care today.
Before developing an intervention program, accurate surveys of need must be done.
This article presents one such needs assessment conducted in a rural section of
the Midwest. The assessment consisted of (1) surveys of HIV+ individuals/people
with AIDS, area physicians, and local key informants and service providers, and
(2) statistical data from health departments. Results of analyses suggest that
access to primary care, self-care education, mental health and family support
services, case management, financial assistance, community education, and home
health services are this community's highest priority needs.
PMID- 10186766
TI - Evaluation of "Hope for a Million Kids Immunization Event: "process, outcome, and
costs.
AB - This study evaluates the Hope For A Million Kids Immunization Event in East
Harlem, New York, in 1996. The methodology: (1) Documented planning and
implementation processes. (2) Analyzed numbers of children reached through the
outreach initiative and those actually immunized due to the Event. (3) Assessed
associated costs. The Event reached and educated 120,000 children through door-to
door canvassing. Substantially fewer children, 562, registered at the Health and
Human Services Fair, and 211 children were immunized at a cost of about $594 per
immunized child. Immunization registries may be more effective in increasing
childhood immunization rates.
PMID- 10186767
TI - Opening new spaces: aging and the millennium.
PMID- 10186768
TI - Area agency on aging outreach and assistance for households with older carers of
an adult with a developmental disability.
AB - A demonstration project was undertaken in the state of New York to assess how
area agencies on aging (AAAs) would approach outreach and direct aid to families
caring for someone with a developmental disability. It was found that AAAs
organized their outreach and direct-aid efforts using three main approaches:
direct operation, contract operations, and multi-organizational. They generally
organized staff time so that about two days per week of effort was devoted to
undertaking outreach activities, conducting community education, and providing
casework and referrals for target families. Four major distinctions were
identified that differentiated work with older carers of persons with a
developmental disability from that with other kinds of carers: complexity of
problems presented by households identified, vagaries of fiscal resources,
diverse household composition, and planning for eventualities. It was concluded
that targeting AAAs for outreach and providing help to these carers was effective
and productive and should be replicated throughout the United States.
PMID- 10186769
TI - The gatekeeper model: implications for social policy.
AB - One of the most important needs of an aging population is to insure that older
adults are able to live as independently and safely as possible. The question for
social policymakers is how to meet this goal in an era of shrinking resources and
growing numbers of older adults. The Gatekeeper Model is highlighted as a method
to insure that older adults at risk of problems that impact their ability to live
independently can be helped by existing systems of care. The model trains
employees of community businesses and corporations who work with the public to
serve as community gatekeepers by identifying and referring community-dwelling
older adults who may be in need of help. A research project was conducted at
Spokane Mental Health, Elder Services Division, where the model was developed.
The results indicate that community-based gatekeepers found 40% of clients.
Gatekeepers find a distinct population of community-dwelling older adults who are
not found by more traditional referral sources. The social policy implications of
the Gatekeeper Model are discussed.
PMID- 10186770
TI - The closing of a social HMO: a case study.
AB - A social health maintenance organization (SHMO) integrates acute and long-term
care and provides an extended-care benefit for elderly who are at risk of
institutionalization. This article reports findings from a case study of the
termination of the Group Health SHMO in Minnesota. Interviews were conducted with
social workers and at-risk elderly who had been receiving long-term care through
the SHMO. The case study examines the post-SHMO transition and the process of
replacing SHMO care coordination and longterm care services. Most of the elderly
and their caregivers indicated they were "losing ground"--that is, they were
paying more or getting less care. Some were paying more for less care. Because
they tended to switch to private-pay arrangements and to rely more on informal
care, it appears that their care system became much less stable after the closing
of the SHMO.
PMID- 10186771
TI - The new Long-Term Care Insurance Program in Germany.
AB - The article describes the new Long-Term Care Insurance Program (LTCI), which has
been operational in Germany since 1995, as well as the policy issues leading to
its enactment. After discussing similarities and differences with the traditional
German social insurance-centered welfare system and some of the major weaknesses
of the new program, two issues are discussed in more detail: (1) entitlement
criteria and reimbursement rules and the ways they influence the conditions and
quality of the professional care delivered; (2) the impact of cash as an
alternative choice to services. The descriptive and evaluative sections use
existing materials and reports; the second section is based, in addition, on a
pilot study by the author, which looks at the reasons why so many people entitled
to LTCI choose the cash alternative.
PMID- 10186772
TI - The outlook for long-term care: doubtful or renewed vigor?
PMID- 10186773
TI - Community responsibility for the self-neglectful client.
AB - Self-neglectful clients, including the elderly, are in jeopardy, partly through
their refusal to accept community services that could help them; they require
protection from the community. These people are alienated and isolated, and need
to be integrated into the community. Their individual rights to control their own
lives, however, must be protected. It is the responsibility of the community to
structure services in a way that will engage these people. A comprehensive
community service program appropriate to their needs would integrate formal and
informal care systems by interweaving professional services, informal assistance,
and mutual aid within structures that facilitate coordination of formal care
programs.
PMID- 10186774
TI - Developing public information on nursing home quality.
AB - The need for greater public information about nursing home quality is growing.
While there are problems in using existing administrative data on nursing home
quality from federal certification surveys, it is probably more feasible to use
such data than to conduct direct surveys of residents and their family members
and friends. Administrative records could be used to provide greater information
on quality than is currently reported by the Health Care Financing
Administration. These records could also be used to develop a rating system for
nursing homes based upon key quality indicators and administrative sanctions.
This challenge is one that should be undertaken to ensure greater access to
information on quality of care in nursing homes and to stimulate efforts by
nursing homes to improve quality.
PMID- 10186775
TI - Meeting the expectations of OBRA.
PMID- 10186776
TI - Regulation of board-and-care homes: research to guide policy.
AB - Information about board-and-care homes reported in the media and in federal
committee hearings indicates that they are shoddy and exploitative environments
that do not provide adequate care. Research done in board-and-care homes in
recent years, however, demonstrates that they can provide adequate care and a
satisfying environment for some of the people they serve. Policy at the federal,
state, and local levels should be guided by both the need to assure the health
and safety of board-and-care residents and the needs of residents and operators
identified in scientific studies.
PMID- 10186777
TI - An intergenerational policy proposal for the 1990s: applying the temporary
disability insurance model to family caregiving.
AB - This paper proposes a new policy initiative to assist family caregivers at a time
when major demographic shifts in both the family and the workplace have taken
place. Women especially are in the position of having to balance both work and
family responsibilities without proper assistance. The initiative is based on an
expansion of the Temporary Disability Insurance (TDI) model, to include care of
family members of all ages by providing an adequate wage replacement. The
shifting dependency ratio, resulting in a shrinking caregiver pool, is discussed
as well as existing policies and their short-comings. For example, no current
policies provide paid leave. The evolution of TDI, including resistance to it, is
examined. Finally, Massachusetts' abortive attempt at a comprehensive plan for
employment-leave insurance is discussed in detail and policy recommendations are
outlined.
PMID- 10186778
TI - State and regional policy implications of elderly migration.
AB - This paper uses the 1980 Census data to estimate the size of the economic
transfers associated with the 1985 to 1990 interregional migration of older
persons. Total economic transfers are estimated by multiplying interregional
migration flows of older persons by the average income of older persons in each
migration stream. Assuming an average life expectancy of 15 years for elderly
migrants and an expenditure multiplier of 2, the total redistribution of income
as a result of 1985 to 1990 elderly migration is estimated to be over $600
billion. The South Atlantic and Mountain regions are the recipients of the
largest positive net transfers; the East North Central and West North Central
regions have the largest negative net transfers.
PMID- 10186779
TI - Does filial piety exist under Chinese communism?
AB - China has been known for centuries for its traditions of respecting the old.
While this tradition has been weakened in the modern era, it still remains as the
most important value underlying the practice of supporting the old in present-day
China. This article looks into the meaning of filial piety, or xiao, and examines
how it has been observed both in the old and modern times. It argues that though
the Chinese communists have found filial piety ideologically repulsive, they have
nevertheless tolerated it and even used it as the basis for a welfare network to
support the elderly in the villages. However, in order to be truthful to their
socialist ideology, they have also provided for urban workers the most
sophisticated state-financed retirement benefits. Two different kinds of systems
to support the elderly hence exist in China. The tensions resulting from this
dichotomous situation are examined.
PMID- 10186780
TI - Social protection for retirees: the diminishing role of employers.
AB - Jobs are changing in ways that will reduce benefits for retirees. This paper
explores the variety of pressures that will tend to produce this result. One
major factor is that employers have been responding to cost pressures and the
need for flexibility by redesigning jobs. There has been a trend--which is likely
to continue--toward more part-time and temporary jobs, more subcontracting, and
more contingent-pay systems. The consequences are complex and not all bad, but
for retirees the tendency will be toward fewer, less generous, or less secure
benefits. As workers approach retirement age facing the prospect of diminished
benefits, increasing numbers of them will have to choose work to maintain their
standard of living. At the same time, demographic pressures will gradually push
employers to seek new pools of workers, including retirees. Gradually, employers
are likely to provide fewer social-protection benefits to older people, but more
employment opportunities.
PMID- 10186781
TI - Serving elders in greatest social and economic need: the challenge to the Elderly
Nutrition Program.
AB - The federally funded Elderly Nutrition Program is mandated to serve elders in
greatest social and economic need. Yet researchers have concluded that the
program underserves certain groups of elders, including those who are socially
impaired and homeless and members of ethnic and other minority groups. This paper
reviews the issues involved in serving elders in greatest social and economic
need and suggests that reaching all of these elders with program services is not
only a laudable goal but also, based on innovative models briefly described, is
clearly achievable.
PMID- 10186782
TI - Free tuition for elders: intentions and effects of the Massachusetts policy.
AB - This analysis explores the development of the elder tuition waiver in
Massachusetts, a policy that established an age-based entitlement to higher
education. The research concludes that the original purpose of the waiver was to
encourage participation, but that there was no expectation that large numbers of
older adults would take advantage of this benefit. Nor, apparently, did advocates
of the waiver seek to assure that a diverse group of older adults would take
advantage of higher education opportunities through the waiver. A review of the
history of the waiver is linked with data on implementation and the results of an
exploratory study of motivations of older college students. The discussion points
to a need for fundamental examination of the practice of providing social
benefits based on age rather than need or universal criteria.
PMID- 10186783
TI - The old in America have no social role.
PMID- 10186784
TI - Accessory apartment conversion programs.
AB - In recent years, state housing finance agencies have joined with state units on
aging to develop programs to help the frail, elderly homeowner. Under an
accessory apartment conversion program, a low-income homeowner will borrow money
at a reduced interest rate to underwrite conversion of excess space into a rental
apartment. The tenant will provide additional income as well as, ideally, certain
kinds of personal assistance and a friendly presence. To date, few elderly
clients have used this option. The initial rationale for the program is explained
as are plausible reasons for the fact that it has not met expectations.
PMID- 10186785
TI - Working in the field of aging policy.
PMID- 10186786
TI - The changing national policy system: complexity, Medicare, and implications for
aging groups.
AB - Changes in congressional processes, health agendas, and competitive positions of
physician and hospital groups in the 1980s have produced important setbacks for
such group interests within Medicare. Though united and successful in opposing
Carter's 1977-79 hospital cost-containment proposals, these groups were subjected
to severe new limits on hospital reimbursements under the 1982 budget
reconciliation act. Thereafter, problems in protecting their interests continued
or increased. Disagreements among hospital groups (e.g., the American Hospital
Association and the former Federation of American Hospitals) surfaced over the
Prospective Payment System introduced in 1983. In 1984, Congress instituted a
freeze on physicians' Medicare fees despite AMA opposition. This projected narrow
self-interest, thus decreasing the AMA's credibility. Further cost restrictions
were imposed in 1985-86 budget acts. The problems of these organizations indicate
that if aging groups are to protect their own stake in Medicare in the new
political context, they must be particularly concerned with unity, credibility,
and long-term perspectives.
PMID- 10186787
TI - Why we should refocus our efforts to improve care in nursing homes.
PMID- 10186788
TI - Accessory Apartment Conversion Programs.
PMID- 10186789
TI - High quality private long-term care insurance: can we get there from here?
AB - The private long-term care insurance market has undergone rapid change in the
last several years. Although the quality of policies has generally improved,
problems remain. Consumer protection issues include the lack of adequate
inflation protection features, how activities of daily living are measured,
potentially high lapse rates and lack of nonforfeiture values, how home care
benefits are defined, and the appropriate loss ratio standards. The concerns of
consumer and elderly advocates about the quality of private long-term care
insurance have prompted congress to consider the need for federal intervention.
While there are numerous approaches that the federal government could take,
mandatory standards substantially higher than the current model standards of the
National Association of Insurance Commissioners may prove the most effective in
improving the quality of policies on a nationwide basis.
PMID- 10186790
TI - The politics of aging: the geriatric imperative of the Department of Veterans
Affairs.
AB - Committed "to care for him who shall have borne the battle and for his widow and
his orphans," the federal government through its veterans' programs has long been
a pacesetter in meeting some of the income-security and health-care needs of
older Americans. But the Department of Veterans Affairs is short of funds. Key
policymakers are genuinely divided over how much more they want to invest in the
care of aging veterans. This paper assesses four options and concludes that it
makes sense to strengthen DVA's internal capacity to meet its geriatric
imperative.
PMID- 10186791
TI - Competency requirements for policy gerontologists: what are the essentials?
AB - "Policy gerontologists" are professionals knowledgeable about both public policy
and aging. Through a survey of potential employers about the education of these
specialists, the authors examined what is desired in terms of knowledge base,
skill proficiencies, and behavioral characteristics. Although a solid knowledge
of aging policies and the policymaking process are considered essential for
policy gerontologists, respondents suggested that communication and political
skills as well as the ability to take initiative and to follow through were also
essential.
PMID- 10186792
TI - State pharmaceutical assistance for the elderly and disabled: planning issues for
program and nonprogram states.
AB - The Medicare Catastrophic Coverage Act (MCCA) would have mandated federal
assistance for Medicare beneficiaries who have high annual prescription
medication costs. High national expenditures for such drugs have encouraged the
development of private and state insurance programs to help with these costs. Ten
state pharmaceutical assistance programs (SPAPs), designed to help certain
elderly, low income, or disabled people, exist for those ineligible for Medicaid
or unable to purchase coverage privately. Coordination of state and federal
benefits was a consideration for established programs, and programs being planned
needed to determine the feasibility of integration of federal assistance. But the
enactment and subsequent appeal of the Act affected both planning and policy
implications for these SPAPs. All U.S. states and territories were surveyed
before the bill's repeal to collect data on the effects of MCCA for those with
prescription drug programs and those without. The repeal of the federal program
places pressure on the nonprogram states to proceed, perhaps more cautiously, to
initiate programs for their own residents, given increasing out-of-pocket and
insurance costs, and no federal program.
PMID- 10186793
TI - Wages or welfare? Compensating caregiving in two conservative social welfare
states.
AB - While nearly all developed nations have some form of attendance allowance for the
elderly and disabled, the United Kingdom and several of the American states have
provisions to pay caregivers directly if they are family members. This paper
compares and contrasts provisions in the U.K. Invalid Care Allowance with
provisions of a program in one American state-Michigan. Such payments potentially
benefit disabled people, caregivers, and cost-conscious states. However, two
particular goals shape the programs' impacts on caregiver functioning and
adequacy. One is the extent to which programs operate as welfare provisions and
benefits directed at the social or household economy. The other is the extent to
which they function as a substitute for wage labor in the market economy. Each of
these can be assessed in relation to the real, personal choices and economic
gains it provides caregivers. Presumably, both are important in sustaining
adequate and satisfying long-term care. Only by truly expanding choice as well as
capacity can governments expect to effectively sustain an optimal mix of care
provision in the community.
PMID- 10186794
TI - Research on aging and human development: hard times, 1991.
PMID- 10186795
TI - Caregivers as comptrollers: women and long-term care and cost containment.
AB - The emphasis on cost containment that was the hallmark of the Reagan
Administration and the shifting of the burden for long-term care onto the
informal sector have had a particularly negative impact on women. Women through
caregiving are used to help control the public cost of long-term care. This
unwritten policy is unlikely to be successful because of a number of factors: (1)
the economic condition of women; (2) the lack of available and affordable
community services; and (3) the types of social relationships we now have.
PMID- 10186796
TI - The Medicare assignment controversy: the construction of public-professional
conflict.
AB - The conflict between the elderly and organized medicine over "mandatory
assignment" and "balance billing" is a significant public policy issue.
Considerable ideological importance has been attached to this conflict by both
sides, despite the relatively modest proportion of total revenue for physician
services received through balance billing in payment for care of Medicare
beneficiaries. The positions of these two coalitions are examined as well as the
efforts of the Physician Payment Review Commission (PPRC) to craft a public
policy response. Three alternative resolutions--those adopted by Congress in 1989
on the recommendation of the PPRC, the Canadian solution, and actions taken on a
state level--are then contrasted. The concentrated impact on the elderly of
balance billing practices is considered as a problem, especially for elderly of
limited income and resources. Justification of the practice is typically provided
by the profession on the ideological grounds of preservation of professional
autonomy rather than economic gain, which also reflects the current relatively
limited use of balance billing; a significant majority of all claims submitted in
the United States are now assigned to physicians. A continuation of the
gradualist strategy of the PPRC is endorsed as the most appropriate short-range
solution to these problems, which diminish in significance with a more
comprehensive national health financing scheme.
PMID- 10186797
TI - Recent OBRA nursing home reforms.
PMID- 10186798
TI - Adding long-term care to Medicare: The Social HMO Experience.
AB - The rancor accompanying the repeal of most of the 1988 Medicare Catastrophic Act
reflects both the national need to improve health and long-term care benefits for
the elderly and the political obstacles to finding new sources of financing for
such benefits. Neither the need nor the obstacles will go away, but policymakers
are now likely to look for lower-cost, efficient, and privately funded
alternatives. The authors have developed and tested one such approach: the Social
Health Maintenance Organization (SHMO). Operating since 1985, the SHMO model
integrates community-based, long-term care services into the managed, prepaid HMO
design. The four test sites are adding long-term care to Medicare at no extra
cost to the government and only modest premiums for the 17,000 current members.
Although the benefits offer limited protection for long-term nursing home care,
they do cover long-term care in community settings, where people tend to prefer
to stay. Also, integration of the acute and long-term care systems improves the
ability to respond to the medical needs of frail members, who also have high
acute-care use. The SHMO's model of front-end, community-oriented, long-term care
benefits integrated with Medicare appears to be a practical, affordable, and
clinically appropriate way to address the rising concern with the lack of
coverage and services for long-term care.
PMID- 10186799
TI - The SHMO outlook: is the cup half full or half empty? Comments in response to
"adding long-term care to Medicare: The Social HMO Experience".
PMID- 10186800
TI - Expanding the focus of health insurance education for Medicare beneficiaries.
AB - Health insurance education plays an important role in helping consumers make
informed decisions about their need for supplemental coverage. This article
reviews findings on the knowledge of Medicare beneficiaries about their health
insurance coverage. Then, current health insurance education programs are
examined with regard to their ability to meet the needs of a competition-based
public policy. Barriers outside the control of individuals that impede the growth
of the long-term care insurance market are identified and the need for an
alternative, broader form of health insurance education is suggested. Changes in
the scope and content of health insurance education are proposed that would
educate the elderly to their own needs as well as the larger policy issues. An
expanded model of education based on the concept of the Swedish study circle is
discussed to illustrate the possibility of combining individual knowledge and
public debate about complex social issues.
PMID- 10186801
TI - Accident prevention among the elderly: moving from HFA Health Policy to social
strategy.
PMID- 10186802
TI - Planning for aging services with dwindling resources--fact or illusion?
PMID- 10186803
TI - Transition in use of human resources in the field of aging.
AB - Through a review of national surveys that address the area of human resource
development in the field of aging, the idea that professional human resources in
the field have not been given adequate attention is discussed. The conclusions
are that with appropriate modifications in educational preparation and personnel
policies and procedures, most aging-specific organizations will be able to more
adequately meet the needs of their clientele despite limited material resources
and the restrictions on the purchase of the time of professional staff.
PMID- 10186804
TI - Elderly volunteers: assessing their potential as an untapped resource.
AB - In these times of dwindling resources for human services, the elderly are
considered by many policy analysts and researchers to be the largest untapped
source for volunteer recruitment. In this article we identify the origins of this
societal expectation, its current actualization, and then analyze factors
contributing to and deterring actual deployment of large numbers of elderly as
volunteers. To assist in this analysis we have employed the conceptual framework
that examines expected age, period, and cohort effects among the elderly on
volunteerism in order to provide a basis for more realistic projections. Our
findings indicate that elderly volunteers cannot be viewed as the cure-all to a
squeeze on economic resources. In light of expected changes in future cohorts,
elderly volunteers can be expected to increase their contribution only if
creative recruitment and training methods will be used by volunteer
administrators.
PMID- 10186805
TI - Services for the elderly in Europe: a cross-national survey.
AB - In 1989, a cross-national comparative survey on services for the elderly in
Europe was initiated and funded by the Commission of the European Communities. It
included the 12 countries of the current European Community (EC). Those services
for the elderly studied were classified as temporary vs. permanent and
conventional vs. innovative residential and community services. This article
discusses developments within the EC relevant to public policymaking on aging and
reports on the services for the elderly examined by the survey. It also
delineates various new tasks for the EC to safeguard the appropriate use of
services and thereby promote a dignified old age for all Europeans involved.
PMID- 10186806
TI - Federalism and aging policy in the 1980s: implications for changing interest
group roles in the 1990s.
AB - Shifts in the American political landscape during the 1980s had impacts on aging
policy and on the behavior of aging interest groups through that decade. But
perhaps even more important are the likely effects of those changes on aging
policy and on the roles of age-related groups in the 1990s--and probably beyond.
First, some of the major policy trends of the 1980s are sketched out, especially
the renewed emphasis on federalism. Then, an assessment of their effects on aging
policy and aging interest groups is provided. Next, a rationale for focusing on
state-level policy and a discussion of current aging interest-group mobilization
at the state level are presented. Last, the prospects for aging interest-group
influence in the 1990s--a period in which the prior decade's emphasis on dual
federalism is likely to continue--is addressed.
PMID- 10186807
TI - Financing long-term care with limited resources: combining the resources of the
public and private sectors.
AB - Under Connecticut's recently implemented public/private partnership to finance
long-term care, individuals will no longer need to impoverish themselves in order
to receive Medicaid assistance. To encourage those people who can afford to buy a
private long-term care insurance policy to do so, the state promises to shield
one dollar in assets from Medicaid "spend-down" rules for every dollar a private
policy pays out for Medicaid-covered services. This article describes the
Partnership, shows how dwindling resources and budget constraints affected the
development of this model, and then contrasts Connecticut's experience with that
of other states and describes what can be learned from this demonstration.
PMID- 10186808
TI - The Older Americans Act: should participants share in the cost of services?
AB - Since its inception in 1965, the Older Americans Act has provided social services
free of charge to older people, regardless of income. In recent years, the
scarcity of resources has sparked a debate as to whether participants who can
afford to pay for services should be required to do so. Of concern is whether
charging fees will change the fundamental nature of these popular programs by
imparting a "welfare" stigma. Other programs that require fees vary enormously by
state, and there has been little documentation of their impact on participation,
equity of service delivery, or public attitudes. In order to evaluate current
proposals, it is necessary to analyze the distributional effects of the cost
sharing system, how the program will be administered, what impact it will have on
service use, which services would be subject to cost sharing and at what income
levels, and what constitutes a "reasonable" fee for service.
PMID- 10186809
TI - Accessory apartment conversion programs.
PMID- 10186810
TI - Forecasting service needs for the year 2000: implications for state government.
AB - This article is based upon research in Florida of the older population and its
projected need for services. It includes discussion of the method and findings of
the study. The focus, however, is on the policy implications for state government
that emerged from the research. The data has enabled Florida to examine the
experience of its own community care programs in order to help develop a
strategic plan for expanding resources, reforming its organization, and improving
its performance. In addition to funding and organization of the state's long-term
care system, the issue of targeting limited community resources to severely frail
elders emerged as a major concern of this research. Although the various states
differ widely in history, demographics, and structure, these policy issues should
be of immediate concern to each of them.
PMID- 10186811
TI - The home care industry: strategies for survival in an era of dwindling resources.
AB - The home care component of our long-term care system is increasingly being
recognized as the preferred alternative to institutional care for the frail
elderly and disabled. Dwindling resources, both human and financial, are likely
to have a deleterious effect on home care. Findings from a 1987-88 survey of
paraprofessional home care workers of the frail elderly in New York City are used
to draw implications for the home care industry. The scope of problems inherent
in the industry imply that changes are necessary on both the micro and macro
levels; the article concludes with recommendations for both levels.
PMID- 10186812
TI - Lessons from the failure of Massachusetts' 1988 Universal Health Insurance Law.
PMID- 10186813
TI - Health care costs of older people: rationing or reform?
PMID- 10186815
TI - Solutions to the shortage of rural doctors.
PMID- 10186814
TI - Helping oneself by helping others: evaluation of a service credit banking
demonstration.
AB - Between 1987 and 1990, the Robert Wood Johnson Foundation funded six service
credit banking demonstration programs among the elderly in which participants
delivered services in return for credits, entitling them to later service. This
evaluation of the demonstrations found that these six sites successfully
attracted elders for the delivery of household support services to a relatively
old, frail population with potentially limited social networks. Evidence on the
significance of the "credit" in attracting volunteers was mixed, but the programs
have attracted new volunteers, and have not substituted for other volunteer
activities. Program development has entailed considerable staff investment in
volunteer support; programs are better understood as community membership
organizations than as mechanical exchanges.
PMID- 10186816
TI - Guardianship reform: does revised legislation make a difference in outcomes for
proposed wards?
AB - There is a lack of critical examination of the efficacy of guardianship reform.
Yet, the awarding of guardianship, especially when it is unwarranted, may deprive
individuals of their most basic civil liberties. This longitudinal research
investigated whether guardianship decisions differed prior to and following
revision of state statutes increasing procedural safeguards. Using data from 766
petitions for guardianship of persons 60 years of age or over from Iowa and
Missouri, it revealed that in most cases, a request for a full guardianship was
tantamount to receiving one. Least restrictive alternatives were seldom employed,
and few petitions were denied either before or after legislative changes. Reasons
for the seeming discrepancy between revised statutes and guardianship decisions
are suggested. No amount of statutory reform, however, will alter the tendency
for society's attitudes toward aging to overshadow and shape the interpretation
and implementation of legislation.
PMID- 10186817
TI - Linking federally assisted housing with services for frail older persons.
AB - Advocates of policies designed to link federally assisted housing with social
services for the frail elderly have encountered barriers such as the historical
separation of housing and services, political and bureaucratic fragmentation, and
budget constraints. Over a 20-year period, they have attempted to address these
issues by identifying the nature and extent of the problem, creating workable
models, and developing a political constituency. Major reform, however, occurred
only in 1990 when Congress passed the landmark National Affordable Housing Act
(NAHA) which provided an "open policy window" for supportive housing legislation.
NAHA's passage, however, still left many issues unresolved (e.g., targeting and
funding for services). The future challenge is to develop new models of
supportive housing and provide a range of residential settings and portable
services to increase the choices for frail older persons.
PMID- 10186818
TI - Productive aging: a feminist critique.
AB - This essay offers a feminist perspective on the call for a "productive aging"
society, and says that the movement provides an answer before we have
systematically asked questions about the meaning of old age. An emphasis on
productivity, among other things, can devalue relational activities, often
inherent in women's roles, and certain older people-older women in particular.
The author proposes a number of measures for the short term, so that society can
be responsible to older women who need and want jobs, as well as ideas for more
far-reaching change.
PMID- 10186819
TI - Social context and personal expenditures for health care: federal policy and the
experience of older adults in the 1970s.
AB - The relationship between the intent and the outcome of legislated social policy
is discussed. Specifically, this study documents some effects of federal health
reimbursement and income policy in the late 1960s and early 1970s on health care
behavior and expenditures in the decade 1970-1980. The Longitudinal Retirement
History Study (LRHS), containing information on a panel of 6,270 men and
unmarried women aged 58 to 63 in 1969, was used to provide information on the
personal health expenditures in this decade. Medicare and Medicaid and the
indexing of Social Security became operational at the beginning of the study,
which permitted the exploration of intended and observed effects of legislation
designed to make health care more accessible and affordable for older adults. As
policy intended, utilization increased over the decade as indicated by both
increases in the number of panelists with health care bills and increases in the
size of total bills (constant dollars). Consistent with federal policy to reduce
personal costs, out-of-pocket expenditures and the proportion of total bills paid
out of pocket decreased. However, the effects of these federal policy initiatives
were constrained by reimbursement rules and the social location of users. For
instance, even at the end of the 1970s, out-of-pocket health care expenditures
across subpopulations persisted. The 1980s and early 1990s have brought increased
concern over the cost of health care and renewed concern over access. Data
suggest that future proposals aimed at providing universal coverage along with
high out-of-pocket costs may not result in equitable programs, and are likely to
have a limited impact on constraining health care costs. The LRHS data indicate
that utilization increased despite continued high out-of-pocket costs for all
except the lower-income groups, who may be limited in their ability to purchase
increasingly costly care.
PMID- 10186820
TI - The aged in the world's constitutions.
AB - This article presents a review of legal provisions benefitting the elderly as
anchored in the constitutions of countries around the globe. While it is of
interest to examine the sheer range of such provisions, it is also possible to
gauge from the comparison whether the presence of constitutional guarantees is
connected with levels of economic development, conditions of population aging, or
other differences among nations. A cross-check with the institutionalization of
social security systems is included in the analysis. The results allow an
assessment of major differences by world regions, an appraisal of unique cases,
and an appreciation of where nations stand today in formulating guarantees and
policies regarding the elderly.
PMID- 10186821
TI - Reported reasons for retirement: a study of recently retired workers.
AB - The normal retirement age in the United States is gradually increasing from 65 to
67 (by the year 2027) as provided by the 1983 Amendments to the Social Security
Act. One can raise the question, "Who will be the most affected by this change?"
This article presents the findings from a study that investigated the
relationship between the primary reason given by recently retired workers for
their retirement and their economic and demographic backgrounds. A logistic
regression analysis was performed using data from the 1982 New Beneficiary Survey
concerning involuntary reasons. A major finding was that economically
disadvantaged workers tended to retire for involuntary reasons. Therefore,
policymakers need to consider the establishment of policies that would protect
such workers from the adverse financial impact of the increase in the normal
retirement age.
PMID- 10186822
TI - Job prospects for mature workers.
AB - Can the economy in the United States generate enough jobs for mature workers who
want to work? This article explores the prospects for jobs first in the high
skill sector and second in the area of contingent work, temporary and part-time
jobs as well as contracting. It concludes that the high-skill market as a whole
will be a source of opportunity to those who are flexible, but within this market
there will be flux in the markets for particular skills. At the other end, the
restructuring of jobs in the American economy is likely to lead to continued
growth in certain forms of contingent labor but the rate of growth will not be
constant and may not always be adequate to employ all those who would like the
employment. Finding and obtaining work will remain a challenge for many older
workers. Those who are flexible and who are willing to acquire new skills will be
the most likely to find opportunities.
PMID- 10186823
TI - Unanswered questions and new directions in research on elderly migration:
economic and demographic perspectives.
AB - The availability of data from the 1990 Census and the Retirement and Health
Survey will afford researchers an unparalleled opportunity to study elderly
migration from several perspectives. This article focuses on economic and
demographic issues. Census data will continue to serve the role of providing
small area data on flows and will permit further disaggregation of behavioral
differences according to age, marital status, and household relationship. They
will also permit disaggregation according to the economic status of individuals
and their households which, coupled with aggregate data on places of origin and
destination, will facilitate comparison between such areas. The RHS data will go
a long way to investigate questions thought to lie at the heart of migration
behavior of older persons, but which have been difficult or impossible to study.
Central to such questions will be the availability of a migration history, which
will permit research on the interaction of migration behavior with critical life
course events such as retirement and the loss of a spouse.
PMID- 10186824
TI - Recognizing the achievements of the Social Health Maintenance Organization (SHMO)
demonstration sites.
PMID- 10186825
TI - Empirical perspectives on services integration and aging: a review.
AB - This article combines a review of social service literature with interviews of
key informants on the issue of integrating services for the elderly into human
services across the life span. Empirical findings concerning the relative
benefits and drawbacks of age-integrated vs. specialized service organizational
structures are emphasized. Surprisingly few empirical studies were identified.
Instead of empirically based reports, the literature is largely comprised of
polemics, which essentially restate long-standing positions on the preferred
handling of integration. A persistent difficulty in discussions of federal and
state service integration objectives has been the wide differences in definitions
of "integration." The lack of data demonstrating that older persons benefit in
integrated service systems, along with substantial progress in development of
specialized services for the aged, suggest that aging advocates should be
cautious in embracing age-integrated service integration proposals. Research
within management information systems oriented toward client outcomes is
necessary to gain valid knowledge of the merits of various integrated service
models.
PMID- 10186826
TI - Over-65 public's awareness of the risks they face for nursing home care.
PMID- 10186827
TI - "De-constructing" family care policy for the elderly: a note.
PMID- 10186828
TI - The changing responsibilities of the state and family toward elders in Hong Kong.
AB - With a predominantly Chinese population and a cultural tradition of respecting
the old, Hong Kong has long relied on the family to support its elderly members.
Economic success has, however, not spared Hong Kong from encountering the same
problems as other industrial societies, such as the loosening of its traditional
values. This article examines the changing responsibilities of the state and the
family in Hong Kong in supporting the old, and in particular, the effectiveness
of the "care in community" policy, which the Hong Kong Government has adopted
since the mid-1970s. The examination concludes that the responsibility must now
be shared between the state and the family.
PMID- 10186829
TI - Under new management: the changing role of the state in the care of older people
in the United Kingdom.
AB - This article examines recent changes and those currently being introduced in the
formal care of older people in the United Kingdom. These are part of a general
trend in all welfare states towards welfare pluralism but, in addition, the
United Kingdom represents something of a special case because of the radical
ideological engine that has driven the restructuring of the role of the state.
The first part of the article outlines the main changes--the promotion of the
private sector, the residualization of the public social services, and the new
managerial role of the state in the care of older people. The second part
considers the implications of these changes for older people and their informal
helpers (or caregivers). The conclusion refers to both the particular changes
taking place in the United Kingdom and, in general terms, to welfare pluralism as
a policy goal.
PMID- 10186830
TI - The effects of federalism on policies for care of the aged in Canada and the
United States.
AB - Debates about who should care for the elderly often center on the relative
responsibilities of the state and family. In federal societies such as Canada and
the United States, however, multiple governments are involved. This article
compares and contrasts federalism in these two nations and its effects on the
division of fiscal, administrative, and programmatic responsibilities for care of
the aged between the national and regional (i.e., state, provincial) governments.
Two major policy arenas, health care and social services, are examined, with
particular attention focused on the roles played by the nongovernmental sector.
Because most care of the aged is provided informally--a situation firmly rooted
in the value systems and public policies of both nations--national and regional
policies that assist family caregivers directly are examined. Policymakers at the
regional level have been more active and often more innovative in constructing
policies that are supportive of family caregiving, but in general, few programs
of direct assistance exist in either nation and these largely depend on their
geographic location. The article concludes with a discussion of the continued
effects of federalism for future policies affecting care of the aged and suggests
some approaches that can be undertaken to empower families in their caregiving
roles.
PMID- 10186831
TI - Eldercare policy between the state and family: Austria.
AB - Certain aspects of the Austrian system of social security and public welfare for
the elderly, on the one hand, and family caregiving, on the other hand, are
reviewed. In 1993, a new attendance allowance act for needy persons is being
introduced in Austria. This reform includes cash payments on seven different
levels according to the degree of need and is supposed to increase the
opportunity of choice for the elderly. This assumption remains dubious; it should
not be expected that a significant number of new informal caregivers can be
recruited. Furthermore, empirical evidence shows that the elderly themselves
clearly prefer the expansion of social services over paid family caregiving.
There is a need for more research regarding the effects of interaction among the
elderly, the family, and professional caregivers and for the promotion of an
empowerment approach.
PMID- 10186832
TI - The evolution of the system of care for the aged in Denmark.
AB - In Denmark, formal services are viewed as a right to be used by any member of
that society who is in need of assistance, premised upon a societal model of
mutual self-help. The focus here is on the dual themes of philosophical
consistency and of transition in the formal system of services and delivery of
care in Denmark. Denmark's system centers on meeting the basic needs of the
elderly while enabling individuals to retain control over decisions regarding
their own lives. It was effective during the economically expansive period of the
1960s and 1970s, but became less effective during the 1980s. Because of the
economic necessity of cutting back on budgets, the national government has in
fact attempted to define and redirect available choices in service delivery. The
dual themes of consistency and dynamism are demonstrated through the case of a
rural municipality in northwest Jutland during the prosperous period into the
more economically limited period of the last decade and the present. Implications
for informal social support and relationships between the aged and their
families, friends, and neighbors in Denmark are explored.
PMID- 10186833
TI - Understanding the pattern of support for the elderly: a comparison between Israel
and Sweden.
AB - Cross-cultural comparison can offer critical input to analyses of the interplay
between formal and informal services for the elderly. Israel and Sweden have very
different population structures and represent different points on the spectrum of
welfare state development: Sweden has a much higher percentage of elderly, a less
traditional family structure, and a much more developed system of public support.
In addition, there are thought to be different attitudes toward family ties, with
a less family-oriented value structure in Sweden. The natural question is to what
extent these differences translate into differences in the extent and nature of
family support for the elderly. In this article, family structure, living
arrangements, disability rates, and formal and informal sources of help in Sweden
and Israel are compared at various points in time. While there is a greater rate
of formal service provision in Sweden and some substitution for family support
seems to have occurred, informal care has nevertheless remained important. In
both countries, residential patterns are critical: it is when the elderly live
alone that the formal system has tended to replace the family. The rate of
institutionalization is particularly important in determining the rate of
disabled elderly requiring care, both formal and informal, in the community.
PMID- 10186834
TI - Implications of shifting health care policy for caregiving in Canada.
AB - The health care system in Canada, like other industrialized countries, is
undergoing a questioning and a change unlike any it has seen for many decades.
This article begins with a brief description of the Canadian health care system,
then discusses the shifts taking place in health care policy, the assumptions
behind these shifts, and the choices that are being made. The current debate
draws on knowledge about seniors and their caregivers. The shifts also have
implications for caregiving, and these are examined. It is concluded that the new
vision of an appropriate health care system that is emerging provides opportunity
for greater recognition of and participation by caregivers. At the same time,
however, it holds the danger that the burden of care will be shifted even more to
their shoulders. It is not yet clear which direction it is going to take.
PMID- 10186835
TI - Social policies regarding caregiving to elders: Canadian contradictions.
AB - In Canada, disparate social policies--to do with health, family, income security,
housing, and so forth--influence caregiving to elders. They are contradictory
policies because of their different objectives, histories, and jurisdictions. The
wider context of societal and socio-demographic changes highlight additional
contradictions in the principles on which social policies regarding caregiving
rest. Some of these contradictions are discussed in terms of policies, their
consequences, whether intended or not, and what the future might hold for
Canadian policies and programs with implications for caregiving to elders.
PMID- 10186836
TI - A global view of changing state and family support for older persons.
PMID- 10186837
TI - Paid family caregiving: a review of progress and policies.
AB - Policymakers in the United States have begun to examine solutions that encourage
increased sharing of caregiving responsibilities between government and family.
Initiatives in Sweden and the United Kingdom are now in place. Support includes a
care leave policy implemented at the federal level, paying salaries to family
members when caregiving is a regular job, providing job training to salaried
caregivers when their personal caregiving experience ends, community-based
programs for caregivers, and allowances to be used for providing care to an
elderly person. In the United States, 13 states pay caregivers as Medicaid
providers. Policymakers have considered tax incentives and, in 1975, U.S. Senate
Bill 1161 was introduced but failed as an attempt to provide cash subsidies to
families caring for the elderly. A proposal has been made to expand the Temporary
Disability Model to include care of family members of all ages by providing
adequate wage replacement to assist caregivers. At present, 34 states provide
some type of economic support for caregivers. Research is needed to determine
what types of programs are most acceptable and beneficial to caregivers as well
as cost effective for government.
PMID- 10186838
TI - Caregiving and long-term health care in the People's Republic of China.
AB - The growing proportion of frail elderly in the People's Republic of China has
necessitated policy of the state toward their long-term care. In this decade,
there has been an increase in the amount of data available on the care and needs
of Chinese frail elders. This article synthesizes these data and traces the
patterns of care of frail elders. It distinguishes between urban and rural
patterns, and identifies the increasing role of the family and community in the
caregiving of elders. State policy, evident from the data, suggests that the
state's role in direct care of elders is minor but that it continues to influence
and support eldercare as part of its policy of promoting the one-child per couple
policy. This process can be seen in support programs for the childless elder, who
symbolizes the expected condition of a large number of future elders under the
one-child policy. The article identifies four factors that are influencing the
changing patterns of long-term care of elders in China: (1) economic reform
programs; (2) the political agenda of the Chinese Communist Party; (3)
differences in urban and rural economic conditions; and (4) policy directed at
long-term investment in health care technology.
PMID- 10186839
TI - Do changing times mean a change in agendas for the elderly?
PMID- 10186840
TI - The generational equity debate: a progressive framing of a conservative issue.
AB - This article discusses the generational equity debate in the United States-
including its origins and the functions it serves. This debate has emerged in the
context of concerns over the aging of the population, budgetary crises, growing
health care costs, increased poverty among children, growing economic inequality,
and declining faith in institutions. By potentially fragmenting support for
Social Security and other social programs, the generational equity approach to
framing public policy issues may serve the interests of those conservatives
wishing to shrink and restructure the American approach to social welfare.
However, the possibility exists that this debate could serve also as a forum to
advance progressive ideas about universal access for persons of all ages to
income and health benefits and employment opportunities.
PMID- 10186841
TI - Subsidized elderly housing: public-private partnerships on the brink.
AB - Starting in the early 1960s, the federal government joined with the private
sector housing developers in a partnership: in return for subsidized mortgages
and tax benefits, developers would rent to low- and moderate-income tenants.
Today, many elderly people live in these "publicly subsidized" units. The initial
agreement, however, held out an escape clause: after 15 to 20 years, for-profit
developers that wanted to end the partnership could prepay their mortgages,
leaving tenants in those buildings "at risk" of rent increases and/or evictions.
This article discusses that partnership, its options for dissolution, and the
current solutions to the problem of the expiring agreements, including a
moratorium, vouchers, and incentives. The compromise legislation responds to all
interested parties--owners, current and would-be tenants, local governments, tax
payers--through a multi-stage sequence of dissolution, yet such a finely tuned,
acutely sensitive legislative solution may not work easily or efficiently.
PMID- 10186842
TI - Resource allocations to the aged according to greatest social need.
AB - The purposes of the study reported on in this article were: (a) to explore the
measurement of social need among the elderly, and (b) to develop an appropriate
method for including social need in funding allocation procedures. Interview
responses from over 4,000 randomly selected elderly persons were used to identify
the demographic correlates of those having the most restrictions in their every
day lives. Procedures for intrastate allocations were developed using variables
suggested by the Older Americans Act and by research to explain variance in
activities of daily living. Variables tested for the model were: age, income,
living arrangement, gender, ethnicity, area of residence, occupation,
hospitalization, years in the neighborhood, language at home, and utilization of
senior services. Prediction formula weights were adjusted (magnitude of beta
i/sigma magnitude of beta i) to allocate resources to the proportions of 10 "high
need" groups residing in each planning area: the population aged 75 and older,
the proportion of hospital discharges of elderly patients, elderly females,
elderly non-Caucasians, the elderly not completing high school, elderly farm
workers, elderly urban residents, a proportion for participation in senior
services, for low-income elderly persons, and for the elderly not living with
their spouses. Compared to current systems, the proposed procedure provides a
closer fit to the actual needs of the elderly.
PMID- 10186843
TI - The effect of age desegregation on environmental quality for elderly living in
public/publicly subsidized housing.
AB - A random sample of elderly living in age-desegregated public housing for the
elderly is compared with a random sample of elderly living in age-homogeneous
Section 202 housing in the same urban area. Findings suggest that the current
trend of mixing young handicapped persons with elderly tenants is associated with
a decline in environmental quality on three dimensions--social networks,
territoriality, and global measures of satisfaction. The differences are not
explained away by pre-existing factors, such as social and economic resources and
service provision.
PMID- 10186845
TI - Dangers lurking in the "continuum of care".
PMID- 10186844
TI - Nonprofit and for-profit home care in Israel: clients' assessments.
AB - Clients' assessments of differences between nonprofit and for-profit
organizations delivering home care services to Israel's frail elderly were
studied. No significant differences were found between nonprofit and for-profit
providers with respect to organizational efficiency; speed of placement and
replacement of home care workers; responsiveness to clients' complaints; and
supervision of care plans, schedules, and service delivery. Systematic
differences were found, however, in clients' perceptions of workers employed by
nonprofit versus for-profit service providers. The differences related to the
home care workers' adaptation to clients' needs and wants; how well workers
delivered services; and how satisfied clients were with the services received.
Indications are that the relatively high efficiency of nonprofit organizations
can largely be attributed to the performance of their home care workers.
PMID- 10186846
TI - Hong Kong and China in 1997: the implications for migration of elderly people
opportunities, constraints, or impetus.
PMID- 10186847
TI - Bearing the costs of our eldercare policies: work constraints among employed
caregivers.
AB - For many caregivers, rendering aid to frail parents, grandparents, siblings, and
spouses comes at a high price: compromised physical and mental health, disturbed
relationships with spouse and children, truncated opportunities for social life,
and, for caregivers who are employed, declining job performance. Using the 1982
National Long Term Care Survey's "Survey of Informal Care-givers," this study
investigates how the sociodemographic characteristics of caregivers, care
requirements, the availability of backup caregivers, and conditions of employment
affect the likelihood that caregivers will suffer work constraints. Estimations
of both the probability of work constraints and hours of work reveal that proxies
for work conditions figure prominently, as do care requirements. In the model of
constrained work, ill health, financial burdens, and primary responsibility for
care are significant determinants; the estimation of hours of work revealed that
low income and competing care demands wielded major influence. Women and white
caregivers are employed fewer hours, while spouses are more likely than other
informal caregivers to face constrained work. Occupation, as an indicator of work
conditions, is shown to be an important addition to the factors considered in
investigations of circumstances that affect caregivers' experiencing work
constraints.
PMID- 10186848
TI - A medicare adult day care model: proposed criteria and available supply.
AB - The study on which this article is based addressed the issue of the proportion of
adult day care centers (ADCs) existing in 1986 that would qualify for Medicare
funding under the 1989 U.S. Senate Medicare Adult Day Care Amendments. It also
estimated the impact of the criteria on two policy-relevant subgroups of ADCs
that is, Alzheimer's vs. non-Alzheimer's and rural vs. urban-using data from a
1986 national census survey of ADCs. The five proposed Medicare criteria and the
percentage of ADCs meeting them were: services to be provided directly, 14.6%;
multi-disciplinary team, 20%; services to be provided directly or indirectly,
16%; program activities, 42%; and other, 53%. Only 3% met all five criteria while
13% met four out of five. Alzheimer's centers met the criteria more often than
non-Alzheimer's centers, while urban centers qualified more often than rural
centers. Based on the findings, implications for Medicare funding policy are
discussed.
PMID- 10186849
TI - What types of hospital patients wait for alternative placement? Findings from an
exploratory case study and policy implications.
AB - Concern about delayed hospital discharges has accentuated since the advent of the
Prospective Payment System (PPS) and resultant hospital underreimbursement for
the care of those patients awaiting alternative placement. This article reports
on ongoing research on the delayed discharge problem. Analyses of the
determinants of the likelihood of delay and the number of days of delay by
patients awaiting alternative placement in 76 North Carolina acute care general
hospitals (about two thirds of all such hospitals) during May 1991 indicate that,
although demographic attributes such as age, race, and sex are important
correlates of delay, which averaged nearly 11 days, a patient's requirement for
heavy care is the most significant policy-relevant variable in explaining the
number of delay days.
PMID- 10186850
TI - Implications of the Social Security amendments of 1983 for older blacks.
AB - The 1983 amendments to the Social Security Act reduced early retirements benefits
and increased the retirement age for future retirees. These changes will
differentially affect various segments of the older population. The author
examines implications of these changes for older blacks, and concludes that
disability and low income are primary factors that put older blacks at risk for
negative consequences as a result of the 1983 amendments. The findings suggest
that blacks are likely to be disproportionately affected by the changes, and that
the changes, as they relate to blacks, do not address the amendments' goals
encouraging private savings and discouraging early retirement.
PMID- 10186851
TI - Net worth and the economic diversity of the elderly.
AB - Using data from the 1984 panel of the Survey of Income and Program Participation
(SIPP), this article examines characteristics of the older population
disaggregated by net-worth quintiles. The authors argue that income is not a
sufficient measure of economic status for current policy discussions on issues
such as changing Medicare co-payments, increasing the taxation of social security
benefits, or means-testing under Medicaid. Net worth is a better measure of
economic status, particularly for the elderly, because it represents the net
value of assets accumulated over the life course. Their results indicate that
there is considerable diversity in the economic status of the older population,
which is masked by aggregate statistics (such as means and medians) typically
used to summarize the economic status of population groups. Stereotypical views
of the elderly based on such aggregates result in misdirected policy formulation.
In the future, policymakers will need to formulate policies and programs using
information on the distributions of income and assets among the older populations
rather than relying on statistical aggregates.
PMID- 10186852
TI - The 1995 White House Conference on Aging.
PMID- 10186853
TI - Public policy for the elderly: are priorities shifting? Unfamiliar choices for
advocates in the 1990s.
PMID- 10186854
TI - Aging policies, entitlements, and the deficit.
AB - Regardless of the good intentions of the Clinton Administration, there will not
be enough money now, or in the foreseeable future, to expand entitlements
adequately and fund domestic programs on the scale desired to meet all, or even
most, needs in health, in housing, in crime control, in welfare, in employment,
and in community-based care. This article examines the source of the problem--the
nonmarket economy. There are three strategies on which societies have
historically relied to fill unmet needs: market incentives, psychological
incentives, and coercion. A fourth strategy, local, tax-exempt currency--called
service credits, or Time Dollars--which combines market incentives and
psychological rewards is described. The article summarizes what we know about why
Time Dollars work. The article recommends that the Clinton Administration use
already mandated and earmarked funds to undertake systematic experimentation with
this currency, using elders to help with the problems of long-term care and
neglected, abandoned, and abused children.
PMID- 10186855
TI - Unifying the poverty line: a critique of maintaining lower poverty standards for
the elderly.
AB - Since 1982, the elderly poverty rate reported by the U.S. Census Bureau has
fallen below the rate for the nonelderly population. This is cited as evidence of
the success of U.S. social policies to benefit the elderly. But lower elderly
poverty rates are an artifact of the fact that a lower, more stringent poverty
line is applied to the elderly living in one- and two-person households, who
constitute 85% of elderly persons. If the same poverty standard is applied to the
elderly as to the nonelderly, the poverty rates are the same or slightly higher.
The poverty line was originally based on the cost of an adequate diet. The lower
standard for the elderly was based on the fact that the elderly consume fewer
calories than nonelderly adults. This article shows there is no justification for
this lower standard, and recommends its elimination. The overall nutrient
requirements of the elderly are not lower, and the elderly spend a higher
proportion of their budgets on food and on other necessities (shelter, health
care) than the nonelderly. Alternative units of analysis examined under different
income-pooling assumptions also show that poverty rates are not lower among the
elderly than the nonelderly.
PMID- 10186856
TI - The Clinton proposal and old-age-based rationing: a plea for informed public
debate.
PMID- 10186857
TI - Recent trends and future prospects for the elderly in Scandinavia.
AB - After World War II, and all through the 1970s, social and economic development in
general, and social policy in particular, raised the standard of living for old
people in Scandinavia considerably. Public provision then leveled off and
declined through the 1980s, with some variation between the countries. While the
aging of the population continues, the political and economic climate now favors
cuts rather than expansion of public budgets. Any further development along these
lines will reinforce the inequalities, and place a growing number of the elderly
and their families at risk.
PMID- 10186858
TI - Medicare and health care reform.
AB - Although Medicare constitutes one of the most popular programs of the federal
government, even its most ardent supporters would likely agree that improvements
could be made and likely should be part of any package of comprehensive health
care reform. While some changes could be made as stand-alone reforms, it would be
better to integrate changes for the under 65-population with those for the
Medicare program. For example, cost-containment strategies would work best if
they applied to the population as a whole rather than creating differences that
lead to cost-shifting and possible discrimination across groups. The generosity
of services covered also ought to be balanced between Medicare and whatever
happens elsewhere. This would allow Medicare's cost-sharing structure to be less
severe in terms of hospital and skilled nursing care, for example. Finally, while
it is tempting to use reductions in spending on Medicare as a means for helping
to finance other expansions, the impact of such changes needs to be carefully
assessed before assuming that they would create no lasting problems. This essay
examines some of the options and likely consequences for Medicare as part of
comprehensive health reform.
PMID- 10186859
TI - Women and social security: a progressive approach.
AB - This article explores some major assumptions underlying the Social Security
system and alternative approaches to rendering the system more economically
viable, meeting the income needs of the elderly and/or providing greater equity
under its benefit and taxation provisions. It attempts to show that the current
structure of Social Security not only reinforces but also exacerbates the
underlying economic inequalities in our nation's political economy under the
guise of a social insurance program. In addressing selected benefit and taxation
issues, the article focuses on how working and older women are faring in the
1990s under the Social Security system. It argues that although the program
theoretically is gender neutral, its impact is not. Women, particularly those who
are single, are poorly served. The article concludes that a progressive
restructuring of the Social Security system itself is imperative if we are to
meet the needs of a large percentage of workers, older people, and the economic
and social demands of the 1990s and beyond. It also offers some suggestions for
such change.
PMID- 10186860
TI - Toward an equitable, universal caregiver policy: the potential of financial
supports for family caregivers.
AB - This article describes the fragmented array of financial supports for family
caregivers currently provided by the federal government, the states, and private
employers-provisions that range from direct payments to tax allowances, dependent
care tax credits, and unpaid leave. It highlights the uneven pattern of supports
available to family caregivers of the elderly, the younger physically disabled,
and children and adults with mental retardation and developmental disabilities
that results from the welfare bias still shaping many current provisions. The
article then critiques current policy and examines the potential for more
explicit family caregiver financial support policy through pending initiatives of
the Clinton Administration.
PMID- 10186861
TI - Options for balancing the OASDI Trust Funds for the long term.
AB - This article explores policy alternatives that can bring Social Security (OASDI)
into long-term balance. The alternatives conform to long-standing principles that
benefits are: an earned right, related to pay and time in the workforce, not
based primarily on need; and related to annual changes in the cost of living.
Furthermore, the OASDI is self-financed, employers and employees contribute
equally, and participation is compulsory. In order to maintain public support,
the policy alternatives also spread the "pain" of change between workers and
beneficiaries, maintain income replacement rates for low-income earners, and
retain a positive correlation between taxes and benefits. The article discusses
varying four policy parameters to balance the funds: the primary insurance
amount, the cost-of-living adjustment; the normal retirement age; and the payroll
tax rate. Only by changing several policy parameters can all the objectives be
satisfied. Discussed in detail are three scenarios, each of which includes a COLA
cut and a pay-as-you-go FICA tax rate.
PMID- 10186862
TI - Decentralization, aging policy, and the age of Clinton.
AB - This article examines the recent trends in decentralization and their
implications for aging policy in the Clinton presidency. It first discusses a
decade-long trend toward decentralizing policy and then examines some recent
federal enactments that promote more discretion by state and local policymakers,
suggesting that these may set the framework for aging policy during most of
Clinton's first term. A basic premise of the discussion is, however, that the
degree of flexibility varies with the policy area being analyzed-housing,
transportation, health and social services--and whether these are "old" (pre
1980s) or "new" (post-1980s) policies. It concludes with the suggestion that a
dual-centered, shared federal-state solution may provide the best approach to the
premier issue in aging policy today-long-term care.
PMID- 10186863
TI - Entitlements, the deficit, and spending caps.
PMID- 10186864
TI - Women and social security: a progressive approach.
PMID- 10186865
TI - Mortality and physical functioning in epidemiologic studies of three older
populations.
AB - Mortality experienced in the first three years of follow-up for three Established
Populations for Epidemiologic Studies of the Elderly (EPESE) is examined in
relation to the participants' self-reported functional ability. In East Boston,
Massachusetts (N = 3,812), Iowa and Washington Counties, Iowa (N = 3,673), and
New Haven, Connecticut (N = 2,812), noninstitutionalized persons aged 65 and
older were asked a series of questions to determine their functional status.
These measures, used in logistic regression analyses of the mortality data,
showed that an increased number of reported disabilities significantly increased
the risk of mortality over and above the effects of the age and sex of the
participant, or the methodological differences among the sites. Disabilities in
gross mobility (e.g., ability to walk a half mile, climb stairs, or perform heavy
work around the house) were more strongly related to mortality than were measures
of activities of daily living.
PMID- 10186866
TI - The Journal and its many contributions over the years.
PMID- 10186867
TI - Productive aging: an overview of the literature.
AB - "Productive aging" describes an array of activities through which older people
contribute to society. Both the extent of current productive activities among
older people and the barriers to more extensive productive activity are reviewed.
If certain adjustments can be made for their special needs, older people have the
potential to make substantial contributions. However, a variety of prejudicial
attitudes and discriminatory practices continue to limit the opportunities of
older people to make productive contributions, particularly in workplace
settings. Interventions are needed to strengthen opportunities for retraining,
employment, and volunteering for older people. At the same time, programs and
policies to facilitate the productive participation of older people cannot easily
correct for the adverse effects of a lifetime of racial or gender discrimination.
PMID- 10186868
TI - Public policy and the plans and preferences of older Americans.
AB - This study compares the retirement plans and preferences of a recent sample of
3,500 men and women of pre-retirement age-50 to 64. The data suggest that a
minority of older workers expect to retire earlier than they really want to, and
that many would delay retirement if they faced different terms and conditions of
employment. Although most older Americans cannot or do not want to work, many do,
and they represent a significant underutilized labor market resource.
PMID- 10186870
TI - Raising the ceiling or raising the floor: extending coverage of community care.
PMID- 10186869
TI - The physical, mental, and social health status of older Chinese: a cross-national
study.
AB - This article reports data on 16 indicators of the physical, mental, and social
health status of older Chinese living in Beijing, Guangzhou, and Los Angeles.
Both the frequency distributions of these indicators and their factor structures
are different among the three cities. These differences may have implications for
the planning of public health services. Either they are the result of differences
in the way in which people in each of these cities think about illness or they
are the result of differential experiences with disease. Although these data
cannot resolve this issue, both the frequency distributions and the severity
ratings for nine chronic diseases also differed markedly among the three cities.
PMID- 10186871
TI - China's agenda for an old-age insurance program in rural areas.
AB - Based on a field study conducted in August 1993 by the author, this article
discusses the experimental program of old-age insurance in rural areas of China.
The achievements made so far, the feasibility of old-age insurance in rural
areas, and the problems encountered by the program are discussed. Policy
recommendations regarding maintenance of the value of the premium, legislation,
management of the program, and continuation of the family support system are
proposed. It is emphasized that China urgently needs to establish a universal old
age insurance program and other social support services for the elderly. This
would be akin to building a new Great Wall to help solve the serious problems of
aging, reverse the trend of a high male-to-female sex ratio at birth, and further
reduce fertility levels in less developed rural areas.
PMID- 10186872
TI - Medicare managed care: a vision for the future.
PMID- 10186873
TI - Informal care substitution: what we don't know can hurt us.
AB - Empirical studies focusing on the relationship between formal and informal home
care do little to quell the fears of policymakers that expanded access to public
home care services will result in the withdrawal of informal support. A close
examination of the studies designed to measure the withdrawal of informal support
justifies this skepticism. Concerns about the withdrawal of informal care may
hinder the introduction of more extensive home care benefits. Researchers have
come some distance in trying to address this policy question. The conflicting
nature of empirical findings, thus far, demonstrates that the answer depends
heavily on how the question is framed, how home care is measured and over what
time frame, and what sorts of analytic approaches are used to model the
relationship between formal and informal community-based care. This article
discusses these issues in greater detail and suggests strategies to address these
problems in future research.
PMID- 10186874
TI - Assisted living: will it reduce long-term care costs?
AB - In their quest to reduce nursing home care expenditures, the various states in
this country have looked to assisted living as a potentially preferred and lower
cost housing alternative for their Medicaid patients. For an assisted-living
program to save costs, states must recognize that some assisted-living residents
will not come from nursing homes, but rather from private residences, resulting
in cost increases. This article argues that this "woodwork effect"--new clients
appearing--is likely to be smaller than the level reported in the home and
community care demonstrations, but that the numbers are difficult to predict with
the possibility of divestiture. It also argues that the true savings from
substitution, or of one form of care for another, depend on the nursing home
reimbursement system in effect at the time.
PMID- 10186875
TI - The print media and aging policy: how differential coverage of Medicare
Catastrophic led congress astray.
AB - This article examines the role of the print media in covering complex policy
issues. Two models of journalism are considered. "Pack journalism" predicts that
print media coverage will be highly consistent in content due to the reliance by
those in the media on the same sources of information. In this article, another
model--"Beltway journalism"--is proposed. It implies that coverage by the print
media indigenous to the Washington, D.C. area (inside the Beltway) will diverge
from that of other print media, presenting a potentially distorted view of the
world to policymakers in Washington. Using the Washington Post and the Los
Angeles Times as possible indicators of the two models, aging policy is addressed
through a case study of newspaper coverage during passage and repeal of the
Medicare Catastrophic Coverage Act of 1988. Findings suggest that Congress was
unduly influenced by the way that Medicare Catastrophic was framed in the
Washington Post, lending credence to the Beltway journalism model. By paying
insufficient attention to the way Medicare Catastrophic was being framed by
sources of print outside the Beltway area, lawmakers allowed themselves to assume
a grassroots-level understanding of the issue and support for the bill, both of
which turned out to be illusory.
PMID- 10186876
TI - Bridge employment and job stopping: evidence from the Harris/Commonwealth Fund
Survey.
AB - This article analyzes a 1989 Louis Harris and Associates survey designed to
elicit information on the employment histories and job-stopping behavior of men
and women who then were approaching or had recently reached retirement age. The
results indicate that retirement often occurs gradually and includes a
substantial period of "bridge employment." Most bridge jobholders work full-time,
by choice, and report high levels of job enjoyment. Occupational mobility
occurring late in life typically involves upward movement, although the pattern
of change is quite different when it takes place outside, rather than within, the
longest job. The principal concern identified in this article is the limited
ability of some groups of workers (nonwhites, females, the less educated, and
those in poorly compensated occupations) to either retain longest jobs or to
obtain acceptable bridge employment. Health problems also frequently lead to
early departures from the labor force.
PMID- 10186877
TI - The challenge of aging and social policy.
PMID- 10186878
TI - Physician case-by-case assignment and participation in Medicare.
AB - The prospect of budget cuts in Medicare is likely to result in less generous
reimbursements from Medicare and thus affects physicians' willingness to accept
Medicare patients with the reduced payments. This study examines physicians'
decisions about case-by-case assignment and participation in Medicare in relation
to Medicare reimbursement generosity. A two-part model is applied to a database
from a national survey of physicians. The results indicate that reimbursement
generosity from private insurance relative to that from Medicare negatively
affects physicians' assignment rates, implying that the elderly's access to
health care and/or the financial burden is likely to be jeopardized by further
reductions in Medicare reimbursements.
PMID- 10186879
TI - Impact of regulation and financing on small board-and-care homes in Maryland.
AB - States use forms of regulation in small board-and-care homes to control quality;
however, quality varies in spite of these efforts. This study of 94 small
facilities compared quality of care measures in homes regulated by a state
administered program with those in nonregulated homes. It also compared homes on
those variables using average payment for services as the independent variable.
Results indicate that higher payments for services had a greater impact on
quality than did participation in a regulatory program. Adequate funding may be
key to maintaining reasonable quality in these homes.
PMID- 10186880
TI - Who is responsible for this? Assigning rights and consequences in elder care.
AB - In the context of providing health and human services for older individuals,
modern American culture often depends on formally asserting and battling over a
clashing array of rights among respective combatants as a first resort at problem
solving. A substantial impediment exists in our cultural environment that
discourages families and professionals, and the agencies that employ them, from
recognizing and respecting the rights of older persons in a less adversarial and
more subtle, sensitive, and flexible manner. This article discusses this barrier,
illustrating it in several aging-related settings, and suggests a paradigm for
addressing the situation. Then, several current challenges to the rethinking of
rights and responsibilities in geriatric and gerontological practice are
acknowledged.
PMID- 10186881
TI - The impact of the social environment on nursing home residents.
AB - This study contrasted the experienced quality of life of residents living on one
of two nursing home units: a unit for those considered socially intact and a unit
combining residents who had moderately impaired cognition or physical function
with those requiring skilled nursing or therapy. Qualitative interviews were held
with residents of both units. The findings indicate that the social environment
of each of the units played a fundamental role in the residents' quality of life.
The social environment affected the residents' conceptions of self, their
interactions with other residents and their interactions with the nursing staff.
The article suggests the processes behind the social environment of each floor
that may have resulted in different perceptions of the quality of life.
PMID- 10186882
TI - Nursing home reform: fait accompli or frontier?
PMID- 10186883
TI - Long-term care: a comparison of policies and services in Israel and the United
Kingdom and implications for the United States.
AB - The issue of long-term care continues to be a main concern in the United States.
As the country wrestles with the development of policies and services, the
experiences of Israel, whose system rests upon national insurance, and that of
the United Kingdom, which is based on grants to local authorities, can act as
valuable teaching aids in the development of programs in the United States.
Although both countries focus on community care with virtually universal access,
concern over resources is forcing each to target their services increasingly to
the most frail. The findings underscore the necessity for accurate planning and
adequate resources if services are to meet the needs of the frail elderly
population.
PMID- 10186884
TI - The impact by race of changing long-term care policy.
AB - Long-term care policy has evolved with little attention to racial differences in
the need for and use of services. Using 1987 National Medical Expenditure Survey
data on nursing home care, formal in-home personal care, and informal-only help,
a model was created to show how different races would use each type of care if:
(1) a universal home-care benefit was established, (2) existing Medicaid home
care benefits were ended, or (3) the income level for Medicaid eligibility was
substantially reduced. Expanded community care benefits would primarily serve
severely disabled older whites. Reductions in long-term care benefits or
eligibility would disproportionately impede access to long-term care for severely
disabled older African-Americans. These differences indicate that race must be
taken into account in long-term care policy initiatives.
PMID- 10186885
TI - Racial differences in retirement income: the roles of public and private income
sources.
AB - Despite great overall improvement in the elderly's economic status over the past
two decades, minority elders still comprise the poorest population group of all.
Nonetheless, the income security of minority elders has not been given special
attention in the scrutiny in recent years of the size and the future of various
federal programs affecting older persons. Based on data from the 1971, 1981, and
1991 public-use data tapes of the Current Population Survey, the racial
difference in income status of the elderly and the role of Social Security and
Supplemental Security income versus that of income from private sources are
analyzed in terms of how income inequality among races is ameliorated or
escalated. The findings show that racial/ethnic differences in income status
increased between 1970 and 1990. The findings also confirm that, for both elderly
singles and couples, Social Security is the most important income source. Without
it, poverty rates among elderly black couples, for example, would have increased
by as much as 48.5 percentage points in 1990. Policies that would help improve
the income status of the low-income elderly are discussed.
PMID- 10186886
TI - The perceived availability, quality, and cost of long-term care services in
America.
AB - This study gathered primary data on the patterns and predictors of home-based,
community-based, and institutional long-term care services for older adults
residing in the United States. A stratified random sample of policymakers and
agency representatives (n = 153; response rate 67.1%) completed a comprehensive
mail survey to provide detailed information on the perceived availability,
quality, and costs of long-term care services in their community settings.
Descriptive analyses revealed that there are significant differences in perceived
access, use, quality, and costs of care by service type and agency affiliation.
The results present an interesting dilemma for policymakers as many of the
services found to be most widely available and of the highest quality were
considered too costly. Implications for public policy and suggestions for further
research are highlighted.
PMID- 10186887
TI - Rural public transportation and the mobility of older persons: paradigms for
policy.
AB - Federal policy regarding public transportation in rural areas is examined through
a comprehensive literature review. Then, three alternative approaches to future
policy are suggested. The current fragmented panoply of rural transit programs
that serve a minority of the rural population is the result of cycles of federal
regulation and deregulation and chronic underfunding of rural transit compared to
urban areas. The public purposes of transit, distinctions of need and demand, and
funding comparisons with automobile usage are some contexts which set the
framework for the social, and economic, and sustainability paradigms. Specific
recommendations within each paradigm are suggested.
PMID- 10186888
TI - Family support for the elderly in China: issues and challenges.
AB - With the introduction of economic reforms, families in China are challenged by a
variety of family-related problems. Demographic and social changes are affecting
both the capacity and willingness of the family to provide care for the elderly.
The Chinese Government is aware of the importance of the family in the welfare of
its citizens, and has promulgated a series of laws and regulations prescribing
family obligations. Yet formal services supporting families are extremely
underdeveloped, and it is urgent that the government formulate an effective
policy to facilitate, support, and maximize family care.
PMID- 10186889
TI - Toward social security reform.
PMID- 10186890
TI - The failed Patient Self-Determination Act and policy alternatives for the right
to die.
AB - The empirical evidence regarding the implementation and impact of the federal
Patient Self-Determination Act is examined in this article. The Act was designed
to increase the use of advance medical directives in light of the U.S. Supreme
Court's Cruzan decision. Research shows that the law has had little effect and
that the use of advance directives has scant relation to medical treatment and
care. Various policy alternatives for the right to die are also examined. The
authors conclude with an analysis of the likely impact of medical costs,
fruitless treatment, and rationed health care on limiting life-prolonging
treatment.
PMID- 10186891
TI - Case management as a force for quality assurance and quality improvement in home
care.
AB - To examine the extent to which case managers engage consciously in quality
assurance activities for the services they purchase or arrange, semi-structured
interviews were conducted with representatives of 75 case management agencies
responsible for allocating home and community-based services with public funds,
and 17 private, fee-for-service case management agencies. Relatively few agencies
had developed formal criteria for defining quality, or systematic ways to assess
it. Several types of quality oversight provided by case managers were identified:
on-site review by case managers themselves, administrative review, and
independent review by quality assurance staff. This article contains examples of
best practices and discusses the policy implications of having case managers
adopt a more explicit and rigorous role in assuring the quality of the services
their clients receive.
PMID- 10186892
TI - Society's search for a legal and ethical basis of physician-assisted suicide.
AB - A review of the way physician-assisted suicide (PAS) is being addressed in the
United States reveals three models, each functioning out of distinctive concepts
of autonomy: (1) litigation, which utilizes philosophical autonomy; (2)
legislation, which utilizes political autonomy; and (3) act of conscience by a
physician, which utilizes consumer autonomy. Each model raises a correspondingly
distinct set of ethical questions and challenges centered around their point of
reference-the judicial system, voters, or the doctor-patient relationship. In the
end, however, efforts to resolve the challenge of PAS will falter if they do not
go beyond these models of autonomy. Religious institutions offer a more
constructive setting for facing the life and death decisionmaking of PAS. The
challenge for religion is to address PAS in solidarity with sufferers,
physicians, and the community, rather than retreating into iconoclastic dogmas.
PMID- 10186893
TI - Regulating older drivers: how are the states coping?
AB - The nation's population is growing older and its dependence upon the automobile
for mobility has never been higher. Traffic safety data indicate that older
operators have more fatal crashes than other age groups. As more people approach
their senior years the safety issues surrounding older drivers will become even
more important. Findings from a 1995 survey are reported identifying the
practices of states and the perceptions of licensing officials concerning the
older driver issue. The results indicate a diversity in approaches and a series
of institutional and behavioral conflicts in the older driver policy subsystem
that contribute to imperfect licensing controls.
PMID- 10186894
TI - Policy instruments for reducing toxic releases. The effectiveness of state
information and enforcement actions.
AB - This article analyzes the extent to which different policy instruments explain
toxic reductions among the states. Data from the Toxics Release Inventory (TRI)
and other sources are used to assess the effect of various policy instruments,
while holding economic factors constant. State TRI information programs,
enforcement action, and direct regulation all matter in reducing toxic releases.
Interestingly, the informational tool seems to matter more than both
authoritative tools. The findings also support the idea that the interaction of
policy instruments as well as the match between policy tools and policy context
may account for a portion of the results.
PMID- 10186895
TI - Reality check. Evaluating a school-based gang prevention model.
AB - The Gang Resistance Education and Training (G.R.E.A.T.) program is a school-based
gang prevention initiative developed in 1991 through the collaborative efforts of
the Bureau of Alcohol, Tobacco, and Firearms, the Federal Law Enforcement
Training Center, and the Phoenix Police Department. Uniformed law enforcement
officers, certified as G.R.E.A.T. instructors, teach the 9-week curriculum to
middle students. In 1994, the National Institute of Justice funded a national
evaluation of the G.R.E.A.T. program. The process evaluation component of this
larger study is reported. First, results of on-site observations of the
G.R.E.A.T. Officer Training program, including an overview of the training
activities, and the authors' assessment of the training process are reported.
Second, observations of the implementation of the program by officers at six
sites are reported. Of primary concern was whether the program delivered to
students was similar to the program taught to the officers during the G.R.E.A.T.
Officer Training.
PMID- 10186896
TI - Cost-benefit and cost-effectiveness analysis of drug abuse treatment services.
AB - The foundations of cost-benefit analysis and cost-effectiveness analysis (CB/CEA)
for drug abuse treatment are developed. An economic model of addict choice and
drug markets is presented. This model is synthesized with the current "cost of
illness" methods used to measure the burden of the disease to society. The
problem of doing cost-effectiveness studies in the presence of large nonhealth
benefits is examined, and guidance is offered to clinical studies with a cost
effectiveness component or to stand-alone cost-effectiveness studies. References
and an extensive bibliography on drug abuse treatment-related CB/CEA studies are
appended.
PMID- 10186897
TI - Evaluation of welfare reform. A framework for addressing the urgent and the
important.
AB - Assessing the effects of changes still emerging under welfare reform and its
overarching policy of devolution presents a challenge to evaluators. Given such
features as time limits and benefits caps that vary widely across states and
communities, it is necessary not only to attend to urgent issues of immediate
relevance for individuals on public assistance but also to focus on important
long-term analyses of this complex intergovernmental set of policies. The authors
present a conceptual framework based on evaluation utilization and illustrate it
with research questions under the rubric of welfare reform. The approach crosses
three types of utilization--conceptual, instrumental, and political--with two
utilization settings--policy adoption and program implementation. Evaluation
strategies are linked to the utilization framework and illustrated with examples
from studies of welfare reform. In the aggregate, evaluation studies represent a
reasonable range of urgent and important issues across most utilization types and
settings.
PMID- 10186898
TI - Research synthesis. Coding and conjectures.
AB - In meta-analyses the extraction and coding of information from primary research
reports has to be completed in a competent way because these tasks implicate most
of the decisions that determine the usefulness of the final product. The authors
offer guidelines that make it more likely that high-quality information is
reliably extracted and coded from primary research reports. These guidelines
address issues ranging from the selection of items and construction of coding
materials to sustaining reliability and vigilance across extended periods of
coding. Thereafter, the authors note how the methodology of meta-analysis results
in pressure to change the type of information that appears in primary research
reports, and close by offering a few conjectures about the future of meta
analysis.
PMID- 10186899
TI - The consistency and uncertainty in examiners' definitions of pass/fail
performance on OSCE (objective structured clinical examination) stations.
AB - The Medical Council of Canada has made use of examiners' pass/fail
classifications of candidates' behaviors in objective structured clinical
examination (OSCE) stations in defining cutting scores for these stations. This
process assumes that there is consistency in the judgments of examiners employed
in the same stations at different testing sites and in the cutting scores derived
from these judgments. These assumptions were tested using the results of the fall
1993 administration of part 2 of the Medical Council of Canada's Evaluating
Examination to 744 candidates. The results of this study provided evidence of the
consistency of the pass/fail and cutting score definitions for the stations used
across examiners.
PMID- 10186900
TI - Can survey data be used to estimate physician practice costs?
AB - Health policy makers rely on survey estimates of physician practice costs to set
reimbursement rates. The Health Care Financing Administration has just funded a
multimillion dollar effort to collect survey data that will be used to revise
payments under the Medicare Fee Schedule. However, the ability of large-scale
physician surveys to obtain accurate information about practice costs is not
apparent. This article examines several of the key obstacles encountered when
trying to obtain accurate estimates. Rates of both unit and item nonresponse over
time are described; in general, there is a trend toward lower unit response rates
and higher item response rates. The article also examines logical inconsistencies
in data. The results suggest that physician surveys may not be the most
appropriate source of data about physician practice expenses. Health policy
makers concerned about provider reimbursement issues should seriously scrutinize
the accuracy of results from physician practice cost surveys. This article
concludes by suggesting alternative methodologies for incorporating physician
practice costs into reimbursement rates.
PMID- 10186901
TI - Long-term findings from Woodridge in reducing illegal cigarette sales to older
minors.
AB - The purpose of the present study is to assess the effectiveness of an enforcement
program in reducing cigarette sales to older minors in a community that had been
successful in reducing illegal sales of cigarettes to younger minors. Cigarette
sales rates were monitored over a 3-year period with quarterly compliance testing
in Woodridge, Illinois. Sales rates for older minors were found to be only
slightly higher than those of younger minors with one exception. These findings
suggest that the enforcement of cigarette control laws is an effective means by
which access to cigarettes can be reduced for both younger and older minors.
PMID- 10186902
TI - A climate survey for medical students. A means to assess change.
AB - An instrument was developed to assess the perceptions of students regarding six
aspects of school climate and their experience of and attitudes toward sexual
harassment and gender insensitivity. During clerkship orientation, 77 students
(92% return rate), half female, were given the survey. Cronbach alpha
reliabilities for the six scales ranged from .71 to .85. One significant
female/male difference among the three scales of general school climate was
observed; two significant female/male differences occurred among the three scales
relating to gender concerns. Seventy percent of both males and females reported
having observed sexually harassing behavior during the previous year; 46% of
females and 15% of males reported experiencing sexually harassing behavior during
the year. Observing and/or personally experiencing sexual harassment was
associated with a decrease in positive climate ratings and an increase in
negative climate ratings.
PMID- 10186903
TI - Using a multimethod approach to measure success in perinatal drug treatment.
AB - In the evaluation study of Options for Recovery (OFR), a comprehensive statewide
initiative to promote perinatal drug and alcohol recovery, a critical step in the
design and implementation of the research was to define and operationalize
indicators of success. Rather than rely on any single evaluation method, a number
of different data-gathering strategies were used to illuminate and provide a
context for data that pertained to a given indicator. Qualitative information,
derived from the interviews with staff and clients, yielded a set of treatment
success indicators that was used to guide the selection of quantitative
variables, as well as provide a contextual understanding of the quantitative
findings. The quantitative findings helped to objectify the qualitative
information. This article discusses the practical application of this multimethod
approach and its effectiveness in measuring client success and illuminating the
complexities of perinatal substance use treatment and recovery.
PMID- 10186904
TI - Dimensions of clinical competence as conceptualized by medical school faculty.
AB - This study identified dimensions of clinical competence underlying faculty
ratings of fourth-year student performance in a standardized patient examination
and assessed the impact of these dimensions on faculty pass/fail decisions.
Content review coupled with exploratory factor analysis was used to group 17 of
25 specific behavioral rating categories into four homogeneous clusters.
Confirmatory factor analysis refined the clusters into four unidimensional scales
that included 14 of the original ratings. The dimensions reflected relating to
the patient, problem-solving skills, medical history skills, and physical
examination skills. The factor structure was cross-validated in a separate data
set. Logistic regression indicated problem solving was the only independent
predictor of a student passing the exercise.
PMID- 10186905
TI - Housestaff social history knowledge. Correlation with evaluation of interpersonal
skills.
AB - It was hypothesized that internal medicine housestaff who inquire into their
hospital patients' social histories would be rated by nurses and attendings as
having better interpersonal skills. Thirty-seven internal medicine housestaff
were asked to answer a questionnaire regarding the social history of up to three
of their hospital patients. The score on these questionnaires was then compared
to evaluations by nurses and attendings of housestaffs' interpersonal skills. We
found that nurses' evaluations of housestaff interpersonal skills correlated with
performance on the social history questionnaire, while attendings' evaluations
did not. Social history inquiry by housestaff may be a marker for housestaff
humanistic and interpersonal skills.
PMID- 10186906
TI - A scale for curriculum evaluation and development in the health professions.
AB - Schools responsible for the education of health professionals throughout the
world are seeking ways to respond to the changing realities of the health
professions and society. In an effort to be responsive to as many people as
possible, there is a need to develop evaluative instruments that are effective
and easily understood by multiple stakeholders. The authors describe the
effective utilization of a simple scale for curricular evaluation, innovation,
and reform. The scale, which incorporates two previously described instruments,
can be used as an aid in several phases of curricular design: (a) during the
development of a statement of educational philosophies that aid in goal and
objective development, (b) during the selection and organization of learning
experiences, and (c) during the evaluation of a curriculum.
PMID- 10186907
TI - USMLE (United States medical licensing examination) step 1 examination. Legal
vulnerability.
AB - Since the passage of the Civil Rights Act of 1964, the courts have ruled that
sponsors of job entry assessment procedures must demonstrate the absence of
discrimination against minorities. If an assessment discriminates, the courts may
prohibit the use of the assessment unless the assessment is linked to a job
analysis and exhibits validity. In 1994, the Federation of State Medical Boards
(FSMB) and the National Board of Medical Examiners (NBME) instituted a three-step
USMLE examination program as a single pathway for medical licensure. The Step 1
examination is not linked to a physician job analysis, exhibits lower scores for
minority groups, and lacks construct validity. To avoid the chaos and expense of
a protracted legal challenge, the FSMB and the NBME may need to revise the Step 1
examination, or discontinue it as a requirement of medical licensure.
PMID- 10186908
TI - Impact studies in continuing education for health professionals. A critique of
the research syntheses.
AB - Documenting impact has been a continual pursuit in continuing education (CE) for
health professionals. Hundreds of primary impact studies have been published,
along with 16 impact study syntheses that have sought to generalize about the
effectiveness of CE and sometimes how and why the effects occur. This article
describes and critiques the methodology of the 16 syntheses and summarizes their
findings. A first wave of syntheses established a general causal connection
between CE and impacts, but explained impact variability only in the dependent
variable-knowledge, competence, performance, or outcome. A second wave added a
search for causal explanation through analysis of variables that moderate impact.
This wave has begun to identify the most appropriate types of programs for
promoting performance changes. The article concludes by suggesting questions and
methods for future primary studies and meta-analyses, including improved
experimental and meta-analytical methods, along with case and naturalistic
studies and action research.
PMID- 10186909
TI - The effect of organizational type and hierarchical level on nurses' perceptions
of hospital issues.
AB - Managers in four acute care hospitals in southeast Florida described the
resource, management, outcome, and external issues confronting their
organizations. Eight major issues and four contributing and resulting subissues
associated with each were identified from the 746 separate issue statements the
managers made. Nurses in the same four hospitals were asked to evaluate the
impact of the eight issues on their organization and their work, as well as the
extent to which the subissues had either contributed to or resulted from the main
ones. Overall perceptual patterns are discussed, as well as the differential
effects of both hospital type and level of employment on perceptions. It is
suggested that differential perceptions among such a key component of the care
delivery system as nurses will need to be better understood as hospitals seek to
survive in a turbulent environment.
PMID- 10186910
TI - A national assessment of the service, support, and housing preferences by persons
with chronic fatigue syndrome. Toward a comprehensive rehabilitation program.
AB - Persons with Chronic Fatigue Syndrome (PWCs) completed and returned by mail a
brief survey of open- and closed-ended items designed to assess their utilization
and preferences for a variety of services. A total of 984 middle-aged adults
diagnosed with Chronic Fatique Syndrome (CFS) from across North America returned
the survey. During the past 12 months, many of these PWCs reported utilization of
a primary care physician, gynecologist, CFS specialist, and self-help group to
assist in their recovery from CFS. Most PWCs believed it was important to educate
both health-care practitioners and the general public about CFS. In terms of
their desire for specific recovery needs, factor analysis of responses indicated
that these PWCs preferred self-help/social support services and general advocacy
services in the treatment of their illness. The implications of these results for
developing rehabilitation programs for PWCs are discussed.
PMID- 10186911
TI - Development and validation of the Diabetes Care Profile.
AB - To determine the reliability and the validity of the Diabetes Care Profile (DCP),
an instrument that assesses the social and psychological factors related to
diabetes and its treatment, two studies with separate populations and
methodologies were conducted. In the first study, the DCP was administered to,
and physiologic measures collected from, individuals with diabetes being cared
for in a community setting (n = 440). In the second study, the DCP and several
previously validated scales were administered to individuals with diabetes
receiving care at a university medical center (n = 352). Cronbach's alphas of
individual DCP scales ranged from .60 to .95 (Study 1) and from .66 to .94 (Study
2). Glycohemoglobin levels correlated with three DCP scales (Study 1). Several
DCP scales discriminated among patients with different levels of disease
severity. The results of the studies indicate that the DCP is a reliable and
valid instrument for measuring the psychosocial factors related to diabetes and
its treatment.
PMID- 10186912
TI - From feedback to reciprocity. Developing a student-centered approach to course
evaluation.
AB - Reforms to medical education have refocused curricula on the need to produce
primary care physicians through a problem-based, student-centered, community
oriented, and integrated approach to instruction. Course evaluations, originally
designed for traditional lecture-based, teacher-centered curricula, provide
inadequate input from students to support curriculum planning and change and to
determine appropriate mixes of educational methods. At the University of Toronto
Faculty of Medicine, a unique community-centered course, called "Health, Illness
and the Community," developed a student-centered course evaluation to provide
adequate student input to support curriculum planning and change. A 35-item
evaluation was developed to obtain data to identify student concerns, student
learning styles, and preferred community agency utilization. The results suggest
that student-centered course evaluation can play a role in managing and
identifying key relationships in integrated and systematic courses as well as
establishing a method for continual improvement.
PMID- 10186913
TI - Relationship between Myers-Briggs psychological traits and use of course
objectives in anatomy and physiology.
AB - The results from the Myers-Briggs Type Indicator (MBTI), which identified
preferred psychological traits for 131 nursing students, were compared to their
usage levels of course objectives in an undergraduate course in anatomy and
physiology. The three usage levels (user, occasional user, and nonuser) were also
compared to exam scores in the course, overall grade point averages (GPA) in
first-year nursing, and the various psychological traits measured by the MBTI. A
multivariate analysis of variance (MANOVA) indicated that users of objectives
achieved significantly higher exam scores and maintained a higher GPA than
occasional and nonusers. The MANOVA also indicated that users of course
objectives preferred a sensing judging modality, whereas nonusers preferred an
intuiting perceiving style to guide their studying and learning.
PMID- 10186914
TI - Federal evaluation of health programs.
PMID- 10186915
TI - Producing credible evaluations of federal health programs.
AB - Based on extensive experience as a reviewer of evaluations of federal health
programs, the author distinguishes and discusses two sources of evidence for the
credibility of an evaluation. Substantive credibility is indicated by the quality
of the literature review; the evaluative understanding manifest in the
description of the program or treatment; the relation between the study questions
and the study design; the expertise and candor displayed in the methods
discussion; and the degree to which stated findings and recommendations are
supported by methods and data. Presentational credibility is undermined by
language that reveals subjectivity or advocacy, but it is supported by the
competent organization and readability of the report.
PMID- 10186916
TI - GAO's role in the evaluation of federal health programs.
AB - The General Accounting Office (GAO) is a legislative branch agency whose mission
is to support the oversight role of Congress. Health policy issues have
constituted a substantial part of GAO's recent workload. Whereas GAO's work on
health has ranged broadly, it has often focused on fraud and abuse in federal
programs, particularly Medicare and Medicaid; the lack of meaningful indicators
and other information, particularly on outcomes in health programs; access to
care, increasingly connected to managed care; quality of care; and issues related
to cost control.
PMID- 10186917
TI - Overcoming barriers to evaluating federal health education and training programs.
AB - The effectiveness of federal programs is often difficult to measure because many
are authorized to support a broad range of objectives without common outcome
goals, measures, and reporting requirements. When direct program evaluation is
not possible, it may be possible instead to evaluate how well the strategies that
federal programs support have worked to achieve certain objectives. This
alternative to direct program evaluation was demonstrated in a General Accounting
Office review of federal health professions education and training programs
within Titles 7 and 8 of the Public Health Service Act.
PMID- 10186918
TI - Evaluation of U.S. Public Health Service programs. Organization and management.
AB - This article provides an overview of evaluation in the Public Health Service
(PHS) of the U.S. Department of Health and Human Services. The kinds of
evaluation activities are outlined with illustrations of recently completed
studies. The overview includes information on resources, policies, and management
of evaluations conducted by the various PHS agencies and programs. In particular,
the department's new efforts to better disseminate evaluation results through the
Internet are described. The article concludes with a discussion of future
prospects of how PHS evaluations will play a role in implementation of the
Government Performance and Results Act (GPRA).
PMID- 10186919
TI - Evaluation in the Health Resources and Services Administration. Improving program
performance.
AB - The mission of the Health Resources and Services Administration (HRSA) in the
U.S. Department of Health and Human Services is to improve the health of the
nation by assuring quality health care to underserved and vulnerable populations
and by promoting a primary care and public health workforce. This article
provides an overview of HRSA's prior work in performance measurement and
highlights a current initiative designed to help the agency improve its
performance measurement efforts in the context of the Government Performance and
Results Act. This initiative began with an agencywide assessment of capacity to
measure performance at program, bureau, and agency levels. Based on the findings,
HRSA is moving forward both with technical assistance to individual bureaus in
developing performance indicators and data sources and with activities to
coordinate performance measurement for the agency as a whole.
PMID- 10186920
TI - Evaluating the Healthy Start program. Design development to evaluative
assessment.
AB - The national evaluation of the federally funded Healthy Start program involved
translating a design for a process and outcomes evaluation and standard maternal
and infant data set, both developed prior to the national evaluation contract
award, into an evaluation design and client data collection protocol that could
be used to evaluate 15 diverse grantees. This article discusses the experience of
creating a process and outcomes evaluation design that was both substantively and
methodologically appropriate given such issues as the diversity of grantees and
their community-based intervention strategies; the process of accessing secondary
data sources, including vital records; the quality of client level data
submissions; and the need to incorporate both qualitative and quantitative
approaches into the evaluation design. The relevance of this experience for the
conduct of other field studies of public health interventions is discussed.
PMID- 10186921
TI - Evaluation in the Substance Abuse and Mental Health Services Administration.
AB - The evaluation policy of the Substance Abuse and Mental Health Services
Administration (SAMHSA) is described in this article. Three studies are presented
that exemplify SAMHSA's evaluations. These include evaluations of a program to
prevent substance abuse among pregnant and postpartum women and their infants; a
Job Corps treatment enrichment program; and the McKinney program for homeless
persons with severe mental illnesses. Each of these evaluations demonstrated the
effectiveness of the programs in reducing substance abuse or homelessness and in
improving the health and well-being of the consumers served. SAMHSA will use the
results of these and similar evaluations to guide policy and program development.
Through its evaluations, SAMHSA must identify effective approaches to prevention,
treatment, and rehabilitation. By using its evaluation results to guide policy
and program development, SAMHSA aims to improve the quality of the public system
of substance abuse and mental health services.
PMID- 10186922
TI - Linking evaluation and program development. The case of AHCPR-supported clinical
practice guidelines.
AB - Within a research organization such as the Agency for Health Care Policy and
Research (AHCPR), the process of evaluating program performance must often be
integrated with a larger research and development agenda. The blending of
evaluation and program development (research and development activities
undertaken to build expertise and knowledge in a specific programmatic area) can
both strengthen the quality of a program and enhance the science of evaluation
research. This article describes AHCPR's evaluation strategy and highlights
evaluation activities for the agency's clinical practice guideline program. A
case study is presented to illustrate the unique methodological challenges in
guideline evaluation, the creation of new tools and approaches for evaluating
clinical quality, and the benefits of linking evaluation research with program
development.
PMID- 10186923
TI - Evaluation of Public Health Service programs under the Government Performance and
Results Act.
AB - The Public Health Service (PHS) is made up of a number of agencies whose
collective mission has traditionally been to protect and improve the mental and
physical health of the American people and to close the gaps in the health status
of disadvantaged populations. However, the Clinton Administration's National
Performance Review and its associated "reinventing government" initiatives are
beginning to show promise of substantially reshaping the structure and functions
of the federal government. Regardless of the final shape that the reinvented
government takes, the Government Performance and Results Act (GRPA) will provide
the framework within which that government plans, implements, and evaluates its
programs. Whereas some have argued that GPRA will strengthen the role of
evaluation within federal agencies, GPRA has been seen primarily as a management
and budget issue, and limited attention has been paid to important issues of
measurement, attribution of outcomes, and reporting time lines. Nevertheless,
GPRA provides the opportunity to make the government more effective and efficient
and restore the faith of the American people in government.
PMID- 10186924
TI - Legal vulnerability of the United States Medical Licensing Examination.
PMID- 10186925
TI - Evaluation of a prospective payment system for VA contract nursing homes.
AB - An evaluation of a pilot program for community nursing home care reimbursement by
Department of Veterans Affairs Medical Centers (VAMCs) was undertaken. Eight
VAMCs began using the Enhanced Prospective Payment System (EPPS) in 1992. These
sites were compared to eight customary payment sites in a pretest/posttest quasi
experimental design. Outcomes included access to care, administrative workload,
quality of care, and cost. As expected, per diem costs were significantly higher
for EPPS than customary reimbursement patients ($106 vs. $87). However, EPPS
sites placed veterans more quickly (81 days vs. 113 days; p < .01) than
comparison sites and reduced administrative workload associated with placement.
EPPS sites also increased the number of Medicare-certified homes under contract
(76% vs. 54%) and placed significantly more veterans who received therapy (20%
vs. < 1%). Savings in hospital days more than offset the increased cost of
nursing home placement. Because the findings were attributed largely to a few
veterans with long lengths of hospital stay, the early success of EPPS may
diminish as the backlog of these long-stay patients decreases.
PMID- 10186926
TI - The limits of Medicaid reimbursement incentives. An evaluation of the Florida
AIDS Nursing Home Admission Program.
AB - Provider incentive payments in the Medicaid program have been in operation
nationally since the early 1980s. Although initially indicating favorable
results, recently the ability of such incentives to produce the desired action
has been questioned. This study examined the Florida Medicaid AIDS Nursing Home
Admission Incentive Program to determine the reasons behind the program's
apparent inability to increase Medicaid-covered persons with AIDS (PWAs)
admissions to nursing homes. A survey of 308 nursing homes in the 10 Florida
counties with the highest cumulative AIDS cases in the state was conducted. The
results reveal that (a) the level of incentive reimbursement received, (b) the
financial classification of existing (non-AIDS) residents, and (c) the level of
technological sophistication of the facility are all significantly related to the
number of PWAs admitted. Based on these results, the author discusses
implications for the future of Medicaid incentive programs for PWAs.
PMID- 10186927
TI - Evaluating HIV prevention community planning.
AB - To improve human immunodeficiency virus (HIV) prevention efforts nationwide, the
Centers for Disease Control and Prevention (CDC) has funded HIV Prevention
Community Planning, an initiative that promotes parity, representativeness, and
inclusion of community and the application of scientific principles for decision
making. This initiative was welcomed enthusiastically in New York City, an AIDS
epicenter with limited prevention resources. In the first year of implementation,
the New York City Department of Health (NYCDOH) supported a comprehensive
evaluation of the planning initiative. This article reviews the evaluation
design, including its process and outcome components, the study findings, and its
strengths and limitations. It provides overall guidance for those who are
assessing prevention planning in HIV as well as other health areas.
PMID- 10186928
TI - Organizational network analysis as a tool for program evaluation.
AB - Health program evaluation is generally focused on an examination of individual
program characteristics and accomplishments, yet many programs are part of a
broader service system. Evaluation of the role a program plays in that system is
an important evaluation question to address. A network analysis of program
referral patterns was used to evaluate Connecticut's Healthy Start program.
Network analysis showed that Healthy Start played a "broker" role in 4 case study
communities, sending and receiving referrals of pregnant women to a higher than
average number of other programs. Further, in the urban area case study,
competing market players providing services to pregnant women resulted in subsets
of services with dense referral patterns within the subsets, but little referral
between subsets. Healthy Start was found to be instrumental as an integrator of
these otherwise disconnected service subsets.
PMID- 10186929
TI - To reward? ... or not to reward?: questioning the wisdom of using external
reinforcement in health promotion programs.
PMID- 10186930
TI - Consumer preferences in format and type of community-based weight control
programs.
AB - PURPOSE: The purpose of this study was to provide further information about
preferences for types and formats (e.g., correspondence vs. face to face) of
eating and exercise programs, actual participation rates in a variety of offered
programs, and characteristics of program participants vs. nonparticipants.
DESIGN: Over a 3-year period, a large sample of community volunteers was given
the opportunity to participate in various forms of diet and exercise programs as
part of a weight gain prevention study. SETTING: The study was conducted at a
university and three local health department sites. SUBJECTS: Subjects in the
study were 616 individuals participating in the Pound of Prevention study (POP),
a 3-year randomized evaluation of an intervention for preventing weight gain.
MEASURES: The primary outcomes assessed were participation rates for each program
offering. Program participants were also compared to those who did not
participate on demographic characteristics, smoking, diet behavior, exercise
behavior, and weight concern. RESULTS: Survey results indicated that
correspondence formats for delivery of health education programs were rated as
more desirable than face-to-face formats. Participation for program offering
ranged from 0 to 16% of the study population. Participation data were consistent
with survey results and showed participants' preference for correspondence
formats even more strongly. Program offering attracted health-conscious
participants with higher education and income levels. CONCLUSIONS: These data
suggest that some community members will get interested and take part in low
cost, minimal contact programs for exercise and weight control. Future research
efforts should focus on investigating ways to increase participation in brief or
minimal contact programs, particularly among groups that may be difficult to
reach and at high risk for the development of obesity.
PMID- 10186931
TI - Longitudinal changes in stages of change for condom use in women.
AB - PURPOSE: This study identifies how women naturally progress through the
Transtheoretical Model stages of condom use over a 1 year period, using the
longitudinal dynamic methodology of latent transition analysis (LTA). DESIGN: As
part of a larger study of human immunodeficiency virus risk in women,
participants were assessed for their stage of condom use two times, 1 year apart.
SUBJECTS: A total of 491 women who completed both assessments of the study were
included in this analysis. MEASURES: Stage of condom use was assessed using two
questions, which placed women into one of five stages of change for condom use
(alpha = .90). RESULTS: Latent transition analysis identified the best-fitting
model of naturalistic stage progression, which included both forward and backward
movement. Precontemplation and maintenance were found to be the most stable
stages (more than 50% of the participants remaining in that stage 1 year later),
and the action stage was the least stable (15% remaining in this stage).
Transition probabilities for all stages showed a high rate of relapse in the
sample. CONCLUSIONS: A high proportion of women will remain within their stage of
condom use over a 1-year period if no intervention is introduced. Interventions
that are aimed at increasing condom use in women need to incorporate relapse
prevention. In addition, the transition probabilities for the stages will help
establish reasonable rates of change for intervention programs.
PMID- 10186932
TI - An organization-based intervention to improve support for employee heart health.
AB - PURPOSE: The purpose of this study was to evaluate the effectiveness of a
management training seminar, developed through a partnership among a college, a
managed care company, and a state public health department, to increase the level
of organizational support for employee heart health in selected companies.
DESIGN: Quasiexperimental. SETTING: Worksites, including heavy and light
industries, school districts, insurance companies, county health agencies, and
health care centers. SUBJECTS: Twenty western New York companies matched on size,
industry type, and interest in worksite health promotion. INTERVENTION: Seven
training seminars held at a college for 1 year and directed primarily at human
resource managers. Training was supplemented by the availability of student
interns, faculty consulting, a vendors' fair, and various program planning aids.
MEASURES: Groups were assessed using HeartCheck, a measure of organizational
support for employee heart health. RESULTS: A fourfold difference in change for
HeartCheck was observed by the experimental vs. comparison groups (p < .01),
along with significantly greater increases on five of the instrument's six
subscales (p < .05). The level of HeartCheck reached in the experimental group
matched those seen in highly acclaimed commercially sponsored programs.
CONCLUSION: This study represents one of the first attempts to intervene at the
organizational level within a worksite health promotion initiative. Positive
results were observed that appear to be both meaningful and cost-effective.
PMID- 10186933
TI - Worksite health promotion programs in the U.S.: factors associated with
availability and participation.
AB - PURPOSE: To examine how the availability of and participation in worksite health
promotion programs varies as a function of individual (e.g., age), organizational
(e.g., occupation), and health (e.g., high blood pressure) characteristics.
Availability of worksite programs was also compared to that reported in two
previous national surveys of private companies. DESIGN: Data analyzed were from
the 1994 National Health Interview Survey (NHIS), a national cross-sectional
probability sample of the U.S. civilian population. SUBJECTS: Five thousand two
hundred nineteen NHIS respondents met the inclusion criteria of (1) being
currently employed in a company of at least 50 employees, and (2) completing the
NHIS section on worksite health promotion. MEASURES: Employees indicated the
availability of, and their participation in, 33 different types of worksite
programs. National Health Interview Survey data were also available regarding
general health, blood pressure, body mass index, and medical conditions. RESULTS:
Smoking cessation programs had the highest mean availability (43%), followed by
health education programs (31%) and screening tests (31%). Overall, availability
of worksite programs appeared comparable to that reported in a recent national
survey. Participation ranged from 32% for health education programs to 5% for
smoking cessation programs. Compared to availability, participation depended less
on individual and organizational characteristics. Healthy employees were not
consistently more likely to participate in worksite health promotion programs
than nonhealthy employees. CONCLUSIONS: Although availability of worksite health
promotion programs remains high, participation by employees in specific types of
programs can vary widely. Attempts to increase participation should look beyond
individual, health, and organizational variables, to specific features of the
work environment that encourage involvement in health promotion activities.
PMID- 10186934
TI - A worksite intervention to enhance social cognitive theory constructs to promote
exercise adherence.
AB - The results suggest social cognitive theory variables associated with the
adoption of exercise are changeable in a brief worksite intervention. Self
regulation techniques and outcome-expectancy value improved, but self-efficacy
did not improve for the treatment group. One possible explanation is, the
intervention did not adequately address the ability to overcome barriers to
exercise faced by participants in the intervention. Another explanation may be
the effect of experiencing the barriers to exercise faced by subjects during the
first 4 weeks of a self-regulated exercise program. Before engaging in exercise,
the participants had a perceived level of confidence to overcome barriers to
exercise. Once faced with real barriers to exercise, the subjects may have
reevaluated their ability to overcome these barriers. It is interesting that the
comparison group reported small decreases in all social cognitive theory
variables measured in this study. The comparison group received a program of
assessment, instruction, and access to facilities that is common to many worksite
based fitness promotion programs. Clearly, this approach did not have a favorable
impact on psychosocial variables associated with exercise adherence. These
results may be explained by a reevaluation of beliefs and perceived capabilities
to exercise, once faced with the real experiences and barriers related to the
adoption of an exercise program. The small decreases in social cognitive theory
variables in the comparison group may explain high dropout rates in many fitness
center programs and warrant further study. IMPLICATIONS: Health promotion
specialists at the worksite need intervention programs that are safe, effective,
and efficient for their employees. This intervention was based in the classroom,
and no exercise was performed during class. This is appealing to employees who do
not have access to shower facilities at the worksite. Moreover, in many
interventions, subjects exercise during class and have limited time to learn
specific skills to help them adopt and maintain exercise outside the structure of
the intervention. Having established favorable changes in social cognitive theory
constructs attributable to the intervention, a follow-up study should be
conducted to determine the extent to which these changes predict adherence to
regular exercise. These studies would establish the causal linkages between
social cognitive theory constructs and regular exercise. LIMITATIONS: There were
specific limitations, and the results should be interpreted cautiously. The
sample size was relatively small, although similar to other exercise intervention
research reviewed by Dishman. Another limitation of the sample was no random
assignment to treatment or comparison group. The results apply only to the
subjects who volunteered for this study. The measure of outcome-expectancy value
is the most vulnerable of those used to measure outcome expectations and outcome
expectancies. It is possible that the results of the study would be substantially
altered if a better measure were available. The data were collected through self
administered questionnaires. It was assumed the subjects would provide accurate
information, but reliance on self-reported data introduces potential sources of
error.
PMID- 10186935
TI - The development and evaluation of lighten up, an Australian community-based
weight management program.
AB - Programs of widely ranging size were conducted successfully in seven localities
and thus the program was considered an operational success. The reductions in
weight, blood pressure, and waist and hip measurements observed at the 3-month
follow-up compared well with reports of other community-based programs. Almost
all participants evaluated the program highly and reported positive changes in
behaviors related to food and exercise. Qualitative data indicate that the
coordinators developed a sense of ownership of the program--which will be vital
to its sustainability. Rapport between coordinators and participants was more
easily established in smaller programs than in larger ones and was an important
underlying determinant of retention rates. SIGNIFICANCE: The Lighten Up program
integrates environmental and individual strategies to facilitate changes towards
a positive, lifestyle approach to long-term weight management. The program aims
to establish sustainable social support networks with effective links to health
services. This study has demonstrated that, with appropriate training and
resources, existing public sector, primary health care personnel with no previous
experience in health promotion can implement the program successfully in several
communities concurrently. In the Australian context, this program can play an
important role as one strategy in a range of interventions required to address
the issue of obesity. The stepped-care model described by Brownell proposes that
program options of varying intensity, and thus cost, be available to meet the
variety of needs of overweight people who wish to lose weight. The Lighten Up
program was close to the midpoint of that range in that it combined population
strategies with one-on-one contact with health care personnel. LIMITATIONS:
Participants in the study were self-selected people who had acted quickly to
enroll in the program, and it is therefore likely that the sample was
overrepresented with early adopters who may have been more successful than others
would have been. We cannot tell from this developmental study whether or not the
program will appeal to population groups known to be at high risk for obesity.
This is an important question that needs to be addressed in future research. No
control group was included in the design and thus we cannot be sure the benefits
experienced by the participants resulted from the program. However, process
evaluation data indicate that nothing that might explain the findings, other than
the program, occurred in the communities during the time of the study. Further
important issues to be evaluated include: the long-term maintenance of weight
loss; whether or not the program will reach targeted populations, particularly
groups of low socioeconomic status; and the extent to which the public health
staff will maintain enthusiasm for the training and the programs.
PMID- 10186936
TI - MR guides intervention and keeps costs down.
PMID- 10186937
TI - Mid-field scanners rival high-field establishment.
PMID- 10186938
TI - High- vs. low-field MR: what's the difference?
PMID- 10186939
TI - Are cost-benefits of PACS real or illusory?
PMID- 10186940
TI - Licensure puts skids on interstate teleradiology.
PMID- 10186941
TI - Single-lead VDD pacemaker implantation via persistent left superior vena cava: an
improved technique and a new modality.
AB - Persistent left superior vena cava (PLSVC), which occurs in approximately 0.5% of
the general population, may complicate pacemaker implantation by making lead
insertion into the right ventricle more difficult and increasing lead instability
when the transvenous approach is attempted. We describe our experience with four
PLSVC patients with pacemakers. We developed an open J-loop technique in which
the stylet tip is directed toward the orifice of the tricuspid valve
anteroinferiorly. The lead was implanted into the right ventricular apex without
difficulty. Three of our patients had high-degree atrioventricular block and
received VVI pacemakers with the new technique. One patient with complete
atrioventricular block received a single-lead VDD pacemaker by means of the same
technique, with the paired electrodes positioned in the lower right atrium.
Excellent results were obtained on exercise tolerance testing, 24-hour Holter
monitoring, and echocardiographically determined systolic and diastolic function.
This improved technique can simplify pacemaker implantation in patients with
PLSVC. The VDD device is a new way to maintain systolic and diastolic function
and is an appropriate option in patients with high-degree atrioventricular block
and PLSVC who require pacemaker implantation.
PMID- 10186942
TI - Differential penetration of skin by topical metronidazole formulations.
AB - This in vitro study compared the release and penetration of various metronidazole
formulations: 0.75% gel, 0.75% cream, and a new 1% cream. Six skin samples from
each of six women (28 to 58 years of age) were used to test the three
formulations, for a total of 12 samples per formulation. A 10-mg target dose of
each metronidazole formulation (75 micrograms of 0.75% gel and 0.75% cream, 100
micrograms of 1% cream) was applied to a skin surface of 1 cm2 per cell. The
randomized application schedule controlled for variability in skin origin,
individual cell thickness, and formulations. Seven fluid samples were collected
over a 15-hour period. Metronidazole concentrations were measured in both the
skin samples and through the fluid from a dynamic diffusion system with the use
of high-performance liquid chromatography method with ultraviolet detection.
Cutaneous penetration of metronidazole was significantly greater with the 0.75%
gel and cream formulations than with the 1% cream. These results suggest that the
delivery vehicle may be more important than the active drug concentration in
cutaneous delivery of metronidazole.
PMID- 10186943
TI - Tizanidine treatment of spasticity: a meta-analysis of controlled, double-blind,
comparative studies with baclofen and diazepam.
AB - To conduct a meta-analysis of the antispastic efficacy and tolerability of
tizanidine, we reviewed records of the European sponsor of tizanidine trials and
selected double-blind, randomized studies of moderate duration in which oral
tizanidine was compared with baclofen or diazepam. Studies were required to have
individual patient data; three key outcome measures (Ashworth Rating Scale for
muscle tone, a measure of muscle strength, and Global Tolerability to Treatment
Rating); and patients with multiple sclerosis or cerebrovascular lesions. Ten
trials involving 270 patients met these criteria. Seven studies used baclofen as
the positive control; three used diazepam. As measured by Total and Lower Body
Ashworth scores, tizanidine and similar spasticity-reducing effects to both
baclofen and diazepam. Muscle strength was affected less by tizanidine than by
either comparator, and investigators judged tizanidine to have greater
tolerability. Within the limits of these comparisons, tizanidine, baclofen, and
diazepam were equally effective in decreasing excessive muscle tone in patients
with multiple sclerosis or cerebrovascular lesions. Muscle strength improved in
all three treatment groups, but improvement was greatest with tizanidine.
PMID- 10186945
TI - Kava-kava extract in anxiety disorders: an outpatient observational study.
AB - Fifty-two outpatients suffering from anxiety of nonpsychotic origin were included
in an observational study of a kava-kava preparation. Drug efficacy was evident
on measures of a global improvement scale, with 42 patients (80.8%) rating
treatment as "very good" or "good". Adverse events were rare. These results
support kava-kava extract as an effective and safe alternative to antidepressants
and tranquilizers in anxiety disorder without the tolerance problems associated
with benzodiazepines.
PMID- 10186944
TI - Effects of hypericum extract HYP 811 in patients with psychovegetative disorders.
AB - The efficacy of tolerability of a 6-week course of Hypericum extract HYP 811 were
investigated in a postmarketing surveillance study of 758 outpatients suffering
from psychovegetative disorders. The investigations included a standardized list
of typical somatic symptoms and global evaluations of the drug's efficacy and
tolerability. By study end, 83.1% of patients had experienced a reduction in
symptom severity, and the frequency of symptoms had improved by an average of
37.3%. After 3 weeks of treatment, the dosage could be reduced to one capsule per
day in 35.8% of patients.
PMID- 10186946
TI - The older patient in the laboratory department.
AB - The elderly patient in the laboratory department often brings special needs. The
accelerated rate of social change, as well as technological changes in the world
in general, have subjected the elderly to an unprecedented need to adapt. The
ability of elderly persons to make effective adaptations is impeded by a society
that places less value on age, resulting in psychological and psychosocial
stresses that do not affect younger individuals. In addition to the pressures of
society, the elderly patient often comes to the laboratory with special needs.
When staff are alert to these special needs and respond therapeutically, the
experience of the elderly patient in the laboratory can be enhanced and positive.
PMID- 10186947
TI - The unscientific emergence of coronary heart disease epidemiology.
PMID- 10186948
TI - A cooperative MLT program between a community college and a university.
AB - In 1991 the University of Utah collaborated with Salt Lake Community College to
establish a jointly sponsored Medical Laboratory Technician (MLT) program. With
documented need for MLTs in Utah and surrounding states, both institutions
combined their resources to create an associate degree program that neither
institution could offer alone. The first academic year of prerequisite science
and liberal education courses are completed at the Community College followed by
a second year of professional didactic and laboratory courses taught by faculty
of the Medical Technology (MT) Program at the University of Utah, Department of
Pathology. Following the second year of professional courses, MLT students
complete 15 weeks of clinical rotations in the Salt Lake Metropolitan area. MLT
students as well as MT students benefit from their shared experiences in combined
courses that are taught on the university campus.
PMID- 10186949
TI - Comparison of four latex kits for detection of E. coli O157.
AB - OBJECTIVE: To compare four Escherichia coli O157 test kits for detection of E.
coli O157:H7 isolated from clinical specimens. DESIGN: One hundred two
Escherichia coli O157:H7 isolates obtained from stored specimens and 99 non
sorbitol fermenting enterobacteriaceae isolates from current clinical specimens
were tested against four latex kits: Wellcolex, RIM, Prolex, and Oxoid. Each
isolate was tested against all four kits on the same day. SETTING: Provincial
Laboratory of Saskatchewan, Canada. PATIENTS: Patients from Saskatchewan with
diarrhea submitted stool specimens through their family physicians to the
Provincial Laboratory for detection of enteric pathogens including E. coli
O157:H7. RESULTS: The sensitivity and specificity of each test kit were:
Wellcolex 100%, 99%; RIM 100%, 99%; Prolex 99%, 100%; Oxoid 100%, 100%. The
Prolex kit failed to detect one E. coli O157:H7 isolate. CONCLUSION: All kits
tested were able to identify E. coli O157 isolated from stool specimens. Further
study with Prolex is needed to assess the significance of the one missed E. coli
O157 isolate.
PMID- 10186950
TI - Surfing the wave of clinical laboratory science evolution in Hawai'i.
AB - OBJECTIVE: To describe the steps taken by the Hawaii Society for Clinical
Laboratory Science, an affiliate of the American Society for Clinical Laboratory
Science, to inform local laboratory professionals of current trends and to
prepare for the future. RESULTS: A Strategic Planning workshop was conducted at
the 1997 Hawaii Society for Clinical Laboratory Science Annual Meeting where
participants reviewed the essential (but non-traditional) functions of clinical
laboratory scientists, and described current realities, identified forces and
players affecting the changes, and envisioned the future of our profession.
CONCLUSION: As the way health care is provided changes in response to economics
and advances in technology, the role of clinical laboratory scientists needs to
be redefined. The Hawaii Society for Clinical Laboratory Science continues to
provide timely support for members, and plans to work collaboratively with the
local chapter of the Clinical Laboratory Managers' Association to advance
clinical laboratory science to an appropriate place in the health care community.
PMID- 10186951
TI - Tracing our roots: a professional identity emerges: 1928 to 1945.
AB - OBJECTIVE: To describe the early years of the American Society of Medical
Technology and discuss major issues that led to contention between the American
Society of Medical Technology and the Board of Registry. DESIGN: A survey of
literature on the history of clinical laboratory science was conducted.
References consulted include various books and professional journals. CONCLUSION:
Clinical laboratory science began to develop a professional identity of its own,
distinct from that of pathology, with the establishment of the American Society
of Medical Technology and the publication of the American Journal of Medical
Technology. These achievements illustrate clinical laboratory scientists'
commitment to developing formal mechanisms to serve their specific interests and
needs, independent of pathologists and the Board of Registry. Pathologists were
successful, however, in maintaining control over other aspects of clinical
laboratory scientists' professional identity, such as certification,
accreditation, scope of practice, and code of ethics.
PMID- 10186952
TI - Development of a computer simulation for laboratory planning.
AB - OBJECTIVE: This study presents a description of a laboratory simulation model and
how it can be used to aid in making management decisions for meeting laboratory
personnel and instrumentation needs to provide the quality of health care
desired. DESIGN: Observations were made and data recorded about resources from
the appropriate areas in the laboratory. The computer model was developed using a
simulation application program. The simulation was then run in three different
configurations to obtain data on how changes in the laboratory may affect
resource usage. SETTING: A 600-bed hospital laboratory was used as the model to
collect initial data. MAIN OUTCOME MEASURES: Measurements were obtained for the
effects of three different employee/instrument mixes to determine the effects of
instrument utilization, employee workload, and specimen turn around time.
RESULTS: The outcomes measured showed varying degrees of resource utilization
versus processing times of specimens. CONCLUSION: Simulation can be an effective
means of providing information to aid the laboratory manager in making decisions
about resource needs in the clinical laboratory.
PMID- 10186953
TI - Learning styles and outcomes in clinical laboratory science.
AB - OBJECTIVE: To compare two learning styles--reflective observation versus active
experimentation--in terms of learning outcomes. DESIGN: The independent variable,
student learning styles, was generally defined as styles determined by use of the
Kolb's Learning Style Inventory. The styles were identified as either active
experimentation or reflective observation. The dependent variables were learning
outcomes that were determined by two methods: the average score on eight
posttests scheduled at periodic intervals and a national certification
examination score. SETTING: Clinical laboratory science education program at the
University of Nebraska Medical Center in Omaha and at six clinical sites in other
cities across Nebraska. PARTICIPANTS: Forty senior clinical laboratory science
students enrolled in a baccalaureate degree program. MAIN OUTCOME MEASURES: Data
analysis consisted of descriptive statistics, two-way analysis of variance, two
way analysis of covariance, and repeated measures analysis of variance. RESULTS:
Results showed no significant difference between the students' examination scores
based on learning styles. There was no significant difference in the pattern of
the examination scores over the semester of learners who were active
experimenters versus reflective observers. CONCLUSION: Results of the study
generally did not support the conclusions of the earlier research; students'
learning styles did not affect their examination scores. No pattern in the
examination scored exists in the learning style groups.
PMID- 10186954
TI - Foodborne illness: is the public at risk?
AB - Millions of people suffer from foodborne illness yearly. While most experience
self-limiting events, others suffer from more serious forms of the disease.
During the past 20 years, the epidemiology of foodborne diseases has evolved as
new pathogens emerged. Factors that have been attributed to the increased risk
for foodborne illness include new food vehicles of transmission, consumer
lifestyles, and eating trends. Low-dose contamination of commercially prepared
food items has caused widespread international outbreaks. In addition, increased
antimicrobial resistance among foodborne pathogens is being recognized. The food
industry and regulatory agencies collaborate in developing effective surveillance
and investigative methods to reduce the risk for foodborne illness.
PMID- 10186955
TI - Emerging foodborne pathogens: enterohemorrhagic Escherichia coli.
AB - In 1982, a new pathogen caused an outbreak of hemorrhagic colitis in this
country. This new pathogen, Escherichia coli O157:H7, was not a known
enteropathogen prior to this time. Since 1982, this organism has become the most
commonly isolated pathogen from patients with bloody stools. Health officials
estimate that E. coli O157:H7 causes 20,000 cases of hemorrhagic colitis annually
in the U.S. Approximately 5% of all hemorrhagic colitis patients experience
serious sequelae involving hemolytic anemia, thrombocytopenia, and kidney
failure, and about 250 patients die each year with E. coli O157:H7 hemorrhagic
colitis and sequelae. Even as many clinical laboratories become more efficient at
detecting E. coli O157:H7 using simple media, other strains of enterohemorrhagic
E. coli are appearing as causes of hemorrhagic colitis and hemolytic uremic
syndrome. These non-O157:H7 are more difficult to detect and identify, and
present a challenge to clinical microbiologists.
PMID- 10186956
TI - The enteric Campylobacter: they are everywhere.
AB - Although Campylobacter spp. are perhaps the most ubiquitous bacterial pathogens
known to man, laboratory diagnosis of Campylobacter enteritis is not particularly
problematic. The organism's ability to thrive at elevated temperatures
facilitates its isolation directly from stool. Enteric infection with
Campylobacter spp., despite its invasive nature, is usually self-limiting in the
otherwise healthy individual. Management of enteric Campylobacter infection,
therefore, is not complex and for most cases simply involves an appropriate
rehydration strategy. In addition to the 'tried and true' approaches of good
sanitation and thorough cooking of meats to prevent Campylobacter infection,
recent advances in vaccine development appear promising.
PMID- 10186957
TI - Fish and shellfish poisoning.
AB - OBJECTIVE: To review history, biology, and medical aspects associated with fish
and shellfish poisoning. DATA SOURCES: Current literature, various Web sites, and
Halstead's Volume II of Poisonous and Venomous Marine Animals. STUDY SELECTION:
Determined by author. DATA SELECTION: Determined by author. DATA SYNTHESIS: Fish
and shellfish poisoning occur through the natural event of the food chain. Fish
and shellfish consume algae that contain toxin-producing dinoflagellates. As a
result they become contaminated and the toxin is concentrated as it moves up the
food chain. Fish and shellfish can tolerate high levels of toxins, thereby
appearing healthy while posing a significant danger to man. The toxin cannot be
detected by sight, smell, or taste and is not destroyed by cooking or freezing.
Thus man becomes an unsuspecting victim. There are several types of poisoning
that occur through fish and shellfish consumption. They are ciguatera and
scombroid fish poisoning; and paralytic, diarrheic, neurotoxic, and amnesic
shellfish poisoning. A different toxin produces each of these poisonings;
however, sources and symptoms may be similar among these poisonings making them
difficult to diagnose. These intoxications can vary in severity from mild to
fatal depending on the type and amount of toxin ingested. Age and underlying
illnesses may also contribute to the outcome of these poisonings. CONCLUSION:
Though people are aware of health warnings and may think they are important, it
is human nature to think that "this could not possibly happen to me". Therefore,
they fail to make the necessary changes required to reduce the incidence of fish
and shellfish poisoning.
PMID- 10186958
TI - Abbreviated aerosol therapy for improved efficiency.
AB - BACKGROUND: The Circulaire nebulizer system (WestMed, Tucson, AZ) has been shown
to minimize the potential for side effects from adrenergic bronchodilator
aerosols by minimizing extrapulmonary deposition. This study evaluates the
utility, safety, and efficacy of a shortened treatment protocol utilizing a timed
treatment with concentrated drug in this device. METHODS: Prospective,
randomized, controlled comparison was conducted of a 2-minute treatment of
concentrated (5 mg/mL) albuterol in the Circulaire nebulizer versus a
conventional unit dose treatment as assessed by pulmonary function testing.
RESULTS: Both treatments were equally efficacious and safe. The abbreviated
treatment consumed about 8 to 10 minutes less and was preferred by patients.
CONCLUSIONS: Abbreviated treatments provide equal bronchodilation with improved
efficiency and potential cost savings.
PMID- 10186959
TI - Metered-dose inhaler add-on devices: an in vitro evaluation of the BronchoAir
inhaler and several spacer devices.
AB - Spacer devices minimize the drug deposition in the oropharyngeal region as they
retain between 30% and 50% of the nominal drug dose. Additionally, they should
increase the fine particle fraction of the emitted aerosol. A new effort to
increase the lung deposition was the design of a new actuator, the BronchoAir
inhaler, (BronchoAir Medizintechnik GmbH, Munich, Germany). This study was
carried out to evaluate the usefulness of this new actuator device by comparing
its fine particle fraction with that emitted with the standard actuators and with
spacer devices. The fine particle fraction's of commercially available metered
dose inhalers (MDIs) marketed with specific spacers were determined using a
multistage liquid impinger (MSLI). The effect of the BronchoAir inhaler on fine
particle fractions was quite dependent on the formulation causing a decrease as
great as 43% with Beclomet forte (beclomethasone-17, 21-dipropionate [BDP]) and
an increase as great as 35% with Arubendol (salbutamol) but causing a difference
of less than 20% with the other six tested formulations. Deposition in the upper
stages of the impinger was sometimes higher than it was for the standard
actuator. Spacer devices decreased the deposition in the upper stages of the
impinger significantly, and in some cases, the fine particle fractions were also
decreased. Varying the spacer design showed the superiority of large-volume open
spacers compared with spacers with other designs.
PMID- 10186960
TI - The effect of flow rate on drug delivery from the Pulvinal, a high-resistance dry
powder inhaler.
AB - Dry powder inhalers vary widely in their resistance to flow. When the resistance
is high, airway resistance can be neglected and inspiration rates will be
determined primarily by the device. Provided that the patient can generate
adequate flow rates to aerosolize the dose, variability of emitted dose and fine
particle dose should be reduced. For in vitro simulation, these concepts are
explored using a Pulvinal device. In conditions likely to be encountered in
patient use, the emitted dose showed little dependence (80-102 micrograms) as the
flow rate increased from 28 to 63 L/min. The fine particle dose was more
sensitive, increasing by a factor of 1.6 from 22 to 35 micrograms. These
variations are less than those observed with the Turbohaler, a device of
intermediate resistance and very much lower than those observed with the
Rotahaler, a low-resistance device.
PMID- 10186962
TI - The Aerosol Society Drug Delivery to the Lungs VIII. London, United Kingdom,
December 15-16, 1997. Abstracts.
PMID- 10186961
TI - Time to peak insulin level, relative bioavailability, and effect of site of
deposition of nebulized insulin in patients with noninsulin-dependent diabetes
mellitus.
AB - Seven fasting patients with noninsulin-dependent diabetes mellitus (NIDDM)
inhaled 1.0 U/kg of body weight of nebulized regular pork insulin by mouth or
were subcutaneously (sc) injected with 0.1 U/kg of body weight of insulin in the
upper arm on two different occasions. The time to peak insulin level was compared
for the two treatment modalities. Insulin bioavailability after inhalation was
quantified relative to sc injected insulin. Deposition of a radiolabeled insulin
surrogate aerosol (insulin diluent) in the larger central airways versus the
peripheral airways, expressed as the inner-to-outer (I:O) ratio, and in the lung
apex versus the lung base, expressed as the apex-to-basal (A:B) ratio, was
quantified with gamma scintigraphy. Ratios were related to glucose responses
after inhalation of insulin. Times to peak insulin level were similar for the two
methods of treatment, averaging 43 +/- 16 and 64 +/- 40 minutes after inhalation
and sc injection of insulin, respectively. The bioavailability of inhaled insulin
averaged 14.7% +/- 5.8% relative to sc injected insulin. This was significantly
less than the average bioavailability of deposited drug (18.9% +/- 5.3%) relative
to sc injected insulin (P < 0.05). I:O and A:B ratios for the surrogate aerosol
averaged 1.3 +/- 0.4 and 0.7 +/- 0.2, respectively. Linear regression analysis
revealed that the maximum percentage of decrease in glucose after insulin
inhalation was significantly related to the A:B ratio such that percentage
decrease in glucose was greater in patients who demonstrated a lower A:B ratio (P
= 0.003). Percentage decrease in glucose was not related to the I:O ratio. These
results indicate that the bioavailability of nebulized insulin inhaled by mouth
is approximately 20% when calculated in terms of drug deposited and suggest that
increasing the distribution of insulin aerosol to the base of the lung enhances
the glucose response in patients with NIDDM during the fasting state.
PMID- 10186963
TI - New laser techniques for diagnosis and treatment of deep-seated brain lesions.
AB - The five years survival rate of deep-seated malignant brain tumors after
surgery/radiotherapy is virtually 100% mortality. Special problems include: (1)
lesions often present late; (2) position: lesions overlies vital structures, so
complete surgical/radiotherapy lesion destruction can damage vital brain-stem
functions; and (3) difficulty in differentiating normal brain from malignant
lesions. This study aimed to use the unique properties of the laser: (a) to
minimize damage during surgical removal of deep-seated brain lesions by operating
via fine optic fibers; and (b) to employ the propensity of certain lasers for
absorption of (nontoxic) dyes and absorption and induction of fluorescence in
some brain substances, to differentiate borders of malignant and normal brain,
for more complete tumor removal. A fine laser endoscopic technique was devised
for removal of brain lesions, which minimized thermal damage and shock waves. A
compatible endoscopic fluoroscopic laser technique was developed to differentiate
brain tumor from normal brain.
PMID- 10186964
TI - Current evaluation of dental implants: a review of the literature.
AB - The literature concerning the success rates and the causes of failure of dental
implants is reviewed in this paper, and the factors influencing clinical outcome
are discussed. Most dental implants seem to be clinically acceptable during the
first few years of installation, as long as the initial healing is uncomplicated.
On a long-term basis, however, osseointegrated implants are the most reliable
among those currently available for routine use. The lack of sufficient
scientific data and well-controlled clinical studies with adequate criteria for
assessing successful outcome are the main reasons why most other dental implants
cannot be clinically recommended without criticism.
PMID- 10186965
TI - Bone formation on HA implants: a commentary.
AB - The present paper reviews bone formation on dense hydroxyapatite (HA) implants.
Calcification of bone matrix formed on HA is different in areas where collagen
fibers are dense and scattered with matrix vesicles than in those interfacial
layers containing few or no collagen fibers and matrix vesicles. Calcification of
collagen-coated areas begins with crystallization within the matrix vesicles. In
contrast, calcification of the interfacial layer is initiated by epitaxial
crystal growth on the HA. Crystallization within the matrix vesicles near the HA
and those on the HA start simultaneously. Calcification of the interfacial layer
is the most important feature of HA as a biomaterial. Such calcification is never
observed on titanium implants. The recent postulation that the rate of bone
formation on calcium-phosphate (CP) ceramics correlates with the solubility of CP
ceramics is improbable, as in vitro immersion tests have been unable to establish
correlation between osteoblast differentiation and the solubility of the CP
ceramics. With regard to HA-plasma spray-coated implants, future research should
focus on the purity of HA and the structure of the ceramics in order to increase
the in vivo chemical and mechanical durability of HA coating.
PMID- 10186966
TI - BIO-OSS--a resorbable bone substitute?
AB - BIO-OSS is an allergen-free bone substitute material of bovine origin, used to
fill bone defects or to reconstruct ridge configurations. Seventy one patients
(39 female, 32 male) received 126 BIO-OSS implantations. Some health parameters
or habits were documented to eliminate possible risk factors of influence. The
diameter of jaw defects filled with BIO-OSS was measured. There was a significant
influence of the defect size on the healing result. In X-ray controls, BIO-OSS
served to identify the surrounding native bone. The density of the BIO-OSS areas
was higher than in control sites. These radiological results were supported by
bone biopsies. Histologically, the permanency of the BIO-OSS was still
recognizable after 6 years and longer. The ingrowth of newly formed bone in the
BIO-OSS scaffold explained the increased density of the implanted regions. There
were no clinical signs of BIO-OSS resorption. Therefore, we can assume that form
corrections achieved by BIO-OSS insertions will last.
PMID- 10186967
TI - Histological findings in guided bone regeneration (GBR) around titanium dental
implants with autogenous bone chips using a new resorbable membrane.
AB - The aim of this study was to test the value of the new polydioxanone-membrane
(PDS, Ethicon, Norderstedt, Germany) in combination with autogenous bone as a
spacer for guided bone regeneration of denuded implant surfaces compared to
simple augmentation. Forty implants were selected for 20 test cases (with
membrane) and 20 control cases (without membrane) and were distributed randomly
in 19 patients who were treated according to a standard protocol and examined.
The defects were filled with autogenous bone chips, harvested interforaminally or
locally, and were covered by the PDS membrane within the test group (control
group: periosteum). The membranes were fixed with Memfix screws and cover screws.
Seven membranes became exposed and were removed before reentry. Within the
control group, three augments were sequestered. After 6 months, reentry was
performed, the healing results were observed clinically, and biopsies were taken.
The test group, including the seven cases with early removal of the membrane,
showed that bone had filled in the defects in 95% of test cases, compared with
60% for the control group. The results of this study show that single
augmentation of defects exceeding 9 mm2 is not sufficient. The membrane used in
this investigation may be helpful for guided bone regeneration (GBR) at denuded
screw thread sites in implant dentistry.
PMID- 10186968
TI - Effectiveness of glycomer 631 monofilament sutures in closing musculoaponeurotic
incisions.
AB - The purpose of this study was to quantitate the effect of two monofilament
synthetic absorbable sutures as well as a new monofilament synthetic absorbable
suture, glycomer 631, in healing musculoaponeurotic incisions in rats. Because
these three monofilament synthetic absorbable sutures provided secure closure of
laparotomy incisions, their clinical use in laparotomy incisions is recommended.
PMID- 10186969
TI - Latex glove penetration by pathogens: a review of the literature.
AB - Universal precautions mandate the use of examination and surgical gloves to
protect the health professional from contact with the HIV virus. The purpose of
this paper is to provide a review of the literature on the barrier properties of
examination and surgical gloves measured by water leakage and viral penetration.
The literature data indicate that glove composition, glove manufacturer, glove
design (examination vs. surgical), and mechanical manipulation had considerable
influence on glove performance when tested for leakage and viral penetration. In
general, latex gloves were found to be superior to vinyl gloves as barriers to
water leakage and viral penetration.
PMID- 10186970
TI - Influence of latex glove hydration on bacteriophage penetration.
AB - The purpose of this study was to determine whether glove hydration influenced
bacteriophage penetration. Using an electronic glove hole-detection device, one
brand of latex glove was identified that hydrated rapidly (3.25 min +/- 0.71
min), while another brand was selected that resisted hydration (120 min +/- 0
min). Using a standard bacteriophage penetration model, the amount of
bacteriophage penetration in both the rapidly hydrating gloves and the gloves
that resisted hydration was extremely small and did not differ significantly from
each other.
PMID- 10186972
TI - The right time and the right place: the concepts and concerns of drug delivery
systems.
AB - The distinction between active drugs and active biomaterials is being gradually
eroded. One of the areas where the interface between drugs and devices needs
greater clarity is controlled delivery of drugs by materials and this article
discusses the basic mechanisms that are involved.
PMID- 10186971
TI - Latex protein levels in external condom catheters.
AB - The Food and Drug Administration (FDA) allows for labeling medical products that
have reduced levels of total water-extractable latex protein. The standard test
method of the American Society for Testing and Materials (ASTM) for analysis of
latex protein in natural rubber and its products is a colorimetric assay with a
precipitation step called the modified Lowry assay. In an analysis of latex
external condom catheters, we have documented a significant difference in protein
levels between two brands of external condoms. The modified Lowry assay is a
significantly less specific method than is an immunochemical assay for measuring
total water-extractable latex proteins. This nonspecificity of the modified Lowry
assay makes it difficult to accurately identify medical products with extremely
low levels of total water-extractable latex protein.
PMID- 10186973
TI - US quality system requirements for software validation.
AB - United States (US) Food and Drug Administration (FDA) investigators have, for
many years, consistently evaluated compliance with US process validation
requirements. Until now there has been significant variability in the manner in
which they have examined compliance with US requirements for the validation of
software used in the production process or as part of the quality system. This
article will discuss the contents of a recent FDA draft guidance document that
may reduce this variability.
PMID- 10186974
TI - Managing the year 2000 problem.
PMID- 10186975
TI - Miniaturization of medical products: the development challenge.
AB - The growing generation of miniaturized medical devices requires developers to re
evaluate their design processes. New products must take account of a non
technical user base, large production volumes, shorter product lifetimes and
pressure to reduce production and purchasing costs. This article looks at some of
the strategies design and development teams can adopt to meet those challenges.
PMID- 10186976
TI - Looking into the future: materials and joining technology.
AB - To improve existing products and create new ones manufacturers of medical devices
need to consider the latest technology and materials. This review of recent
developments in joining techniques describes alternative joining processes and
how to establish best practice when working with adhesives and welding.
PMID- 10186977
TI - Managed care: has the revolution arrived?
AB - Managed Care has been predicted to become the single most important issue by the
end of the century. Is there any evidence to suggest that this is happening? In
this article, the author reviews recent health-care cost containment initiatives
and merger and acquisition activity. A profile of the market in the United States
and evidence of policy changes in the United Kingdom also illustrate the trends.
PMID- 10186978
TI - Medical devices in the UK: a healthy industry.
PMID- 10186979
TI - The responsibilities of importers and distributors.
AB - The European Directives for medical devices impose significant responsibilities
on manufacturers, Member States and Notified Bodies. However, the Directives
define far fewer responsibilities for importers and distributors. As a result,
manufacturers and distributors do not always have a clear concept of these
responsibilities nor of those specified by national laws and regulations. This
article will discuss these responsibilities and some issues that should be
considered in determining them.
PMID- 10186980
TI - New aspects of biocompatibility testing: where should it be going?
AB - In vitro tests that employ permanent cell lines represent a necessary, but
primitive, first step in biocompatibility testing. Progress needs to be made in
biofunctionality testing with respect to the final host, the human organism. This
article looks at the principles and possibilities of in vitro test systems.
Existing methods of cell and molecular biology are essential steps towards
reducing animal experimentation. The potential of new in vivo models, such as
genetically engineered animals, is also evaluated as a bridge between in vitro
testing and the final application in the human body.
PMID- 10186981
TI - Testing for technical files: avoiding too little and too much.
AB - Since 13 June 1998, it has been mandatory for all new and existing medical
devices to be CE-marked according to the Medical Device Directive. However, for
certain electromedical devices full compliance with the requirements of EN 60601
1 as a means of obtaining the CE mark may not be necessary. This article looks at
some of these products and explains how they may still qualify for distribution
in the European medical market.
PMID- 10186982
TI - Medical devices in France. Reform and regulation.
PMID- 10186983
TI - Regulating human-tissue products in France.
AB - The absence of a pan-European regulatory framework for medical devices
incorporating human tissues is causing difficulties for the growing number of
manufacturers of these products. France has implemented strict legislation in
this area and is spearheading an effort for Member States to adopt similar
measures. This article looks at the status of French regulations, which form the
basis of its recent proposal to the European Commission for a new Directive on
human tissues.
PMID- 10186984
TI - The surgical gowns and drapes of tomorrow. Specifying material performance and
test methods.
AB - A mandatory European standard is being developed to establish basic requirements
and test methods for disposable and reusable materials used for surgical gowns
and drapes. Once this standard has been adopted, the continued use of cotton
textiles and conventional cotton-polyester-mixed textiles will become
questionable. This article outlines the proposed requirements and looks at
alternative methods that use liquid-repellent micro-filament textiles or liquid
proof textile laminates.
PMID- 10186985
TI - Growth in the biomaterials market: the nature of growth factors.
AB - An increasing number of medical devices are demonstrating better performance if
they are used in association with growth factors. This is especially so in the
area of tissue regeneration. This article describes the nature of these molecules
and discusses some of the issues associated with their incorporation into medical
devices.
PMID- 10186986
TI - Process validation: harmonizing the requirements.
AB - Medical device manufacturers marketing in Europe and the United States are faced
with differing expectations regarding the quality system requirements for process
validation. However, this may change as a result of a process validation guidance
document being developed by the Global Harmonization Task Force. This article
will discuss the document's current status, some of its elements and some
suggested modifications.
PMID- 10186987
TI - A tale of two markets: predicting the future of medical disposables.
PMID- 10186988
TI - Metallocene-catalysed cyclo-olefin copolymers.
AB - Metallocene-catalysed cyclo-olefin copolymers offer medical product designers a
substantial range of properties. This article outlines the capabilities of these
materials and describes the advances in chemical engineering that allowed their
mass production. A range of applications are highlighted.
PMID- 10186989
TI - Clinical evaluation or investigation?
AB - For devices undergoing clinical investigation in the European Union,
manufacturers must comply with the requirements of the Medical Device Directive.
In certain Member States, the Competent Authority reserves the right to perform a
pre-assessment of clinical information together with a technical review of the
proposed device. Inadequacies in these submissions remain the single most common
reason for rejection.
PMID- 10186990
TI - CAD in the medical device industry.
AB - For those who began designing medical devices on a drawing board, the rate of
development in the passing generations of computer-aided design (CAD) packages
has been startling. Increasing processing power on the desktop has allowed CAD to
provide flexible, powerful and affordable product design to a widening user base.
This article looks at the expanding features of this software and the advantages
it offers.
PMID- 10186991
TI - Rising to the surface: the technology of polymeric surfaces on biomaterials.
AB - The properties of a piece of plastic may generally be highly appropriate for a
medical application except that its surface may not be optimal. Some of the many
ways in which the surfaces of biomaterials can be modified so that the main bulk
properties are undisturbed and specialist surface properties exist in a thin,
often invisible, layer are described in this article.
PMID- 10186992
TI - Emergency Medical Services System in Hong Kong: a pearl in the South China Sea.
AB - Each Emergency Medical Services (EMS) system is unique in its development and
scope of practice. In many instances, it incorporates components of other models.
It is important to the intellectual growth of the Emergency Medical Technicians
that they visualize EMS design from an international perspective. This article
describes the EMS system that exists in Hong Kong. It explores the changes that
are occurring, defines the relationship between Hong Kong and China, and
considers the influence that this evolving model might have on China after 1997.
PMID- 10186993
TI - The Gulf War: the experience of a department of anesthesiology in the management
of Scud missile casualties.
AB - BACKGROUND: The pivotal role of anesthesiologists in the implementation of
disaster plans is not widely appreciated. OBJECTIVE: To describe the role of
anesthesiologists as managers in the operating room (OR) especially during
hospital disaster management. METHODS: On 25 February 1991, King Fahd Hospital of
the University in Eastern Saudi Arabia, was alerted, received, triaged, and
treated the victims of a Scud missile attack on a United States military barracks
which killed 28 and injured more than 100 service personnel. RESULTS: There were
47 males and 15 females admitted to the hospital. Their initial triage categories
of injuries were: 1) red, 23; 2) yellow, 27; and 3) green, 7. The flow of
patients through the main operating rooms occurred in two peaks: 1) treated
within nine hours (60%); and 2) during the next 11 hours (40%). A total 101 units
of blood and blood products were consumed. The role of the Chief of
Anesthesiology was vital in the dynamics of the situation regarding appropriate
deployment of staff and ensuring an orderly throughput of victims in the
operating room. He also was required to keep track of resources and supply levels
in the operating room, so that he could advise the hospital administration
appropriately. CONCLUSION: The successful management of a large multi-casualty
incident, which involved use of the operating rooms, depended upon the efficient
coordination of clearly defined functions with the Chief of Anesthesiology
Service as the team leader.
PMID- 10186994
TI - A model for a statewide critical incident stress (CIS) debriefing program for
emergency services personnel.
AB - PURPOSE: Emergency services personnel are highly vulnerable to acute and
cumulative critical incident stress (CIS) that can manifest as anger, guilt,
depression, and impaired decision-making, and, in certain instances, job loss.
Interventions designed to identify such distress and restore psychological
functioning becomes imperative. METHODS: A statewide debriefing team was formed
in 1988 through a collaborative effort between an academic department of
emergency medicine and a social work department of a teaching hospital, and a
metropolitan area fire department and ambulance service. Using an existing CIS
debriefing model, 84 prescreened, mental health professionals and emergency
services personnel were provided with 16 hours of training and were grouped into
regional teams. Debriefing requests are received through a central number
answered by a communicator in a 24-hour communications center located within the
emergency department. Debriefings are conducted 48-72 hours after the event for
specific types of incidents. Follow-up telephone calls are made by the debriefing
team leader two to three weeks following a debriefing. The teams rely on
donations to pay for travel and meals. RESULTS: One hundred sixty-eight
debriefings were conducted during the first four years. Rural agencies accounted
for 116 (69%) requests. During this period, 1,514 individuals were debriefed: 744
(49%) firefighters, 460 (30%) EMTs, and 310 (21%) police officers, dispatchers,
and other responders. Deaths of children, extraordinary events, and incidents
involving victims known to the responders (35%, 14%, and 14% respectively) were
the most common reasons for requesting debriefings. Feedback was received from 48
(28%) of the agencies that requested the debriefing. All of those who responded
felt that the debriefing had a beneficial effect on its personnel. Specific
individuals identified by agency representatives as having the greatest
difficulty were observed to be returned to their pre-incident state. CONCLUSIONS:
CIS debriefings are judged as beneficial. A statewide response team is an
effective way to provide these services at no cost to agencies.
PMID- 10186995
TI - Lessons learned and unsolved public health problems after large-scale disasters.
AB - BACKGROUND: This paper examines the considerable medical and psychological
problems that ensue after disasters in which massive populations are affected for
extended and sometimes unknown time periods. The organization of disaster
response teams after large-scale disasters is based on experiences as a medical
specialist at Chernobyl immediately after this catastrophe. Optimal ways of
dealing with the immediate medical and logistical demands as well as long-term
public health problems are explored with a particular focus on radiation
disasters. Other lessons learned from Chernobyl are explained. ISSUES: Current
concerns involve the constant threat of a disaster posed by aging nuclear
facilities and nuclear and chemical disarmament activities. The strategies that
have been used by various groups in responding to a disaster and dealing with
medical and psychological health effects at different disaster stages are
evaluated. The emergence of specialized centers in the former Soviet Union to
study long-term health effects after radiation accidents are described.
Worldwide, there has been relatively little attention paid to mid- and long-term
health effects, particularly the psychological stress effects. Problems in
conducting longitudinal health research are explored. RECOMMENDATIONS: The use of
a mobile diagnostic and continuously operating pre-hospital triage system for
rapid health screening of large populations at different stages after a large
scale disaster is advisable. The functional systems of the body to be observed at
different stages after a radiation disaster are specified. There is a
particularly strong need for continued medical and psychosocial evaluation of
radiation-exposed populations over an extended time and a need for international
collaboration among investigators.
PMID- 10186996
TI - Relationship between battery capacity and the delivery of shocks in prehospital
defibrillators.
AB - STUDY OBJECTIVE: Automatic external defibrillators (AED) have enabled the medical
act of defibrillation to be performed in the community by a number of non
physician providers. However, these portable, battery-powered units are costly to
maintain and service. This study examines the life of AED batteries and provides
a battery replacement protocol. DESIGN: Prospective diagnostic testing of 191
field batteries to determine their ability to deliver shocks at 360 joule.
SETTING: Ottawa General Hospital Paramedic Program. OUTCOMES: Using a battery
analyzer, battery capacity and the number of shocks delivered were determined for
each battery (at room temperature and in a controlled, refrigerated setting). In
addition, the reliability of the testing method was assessed using the interclass
correlation coefficient (ICC). RESULTS: High reliability of blinded technical
assessment of the batteries was achieved (ICC = 0.85). A strong correlation
between the battery's capacity and the number of shocks it can deliver was
obtained. For example, a battery with a measured capacity of 75% is capable of
delivering more than 30 consecutive 360 joule shocks. This compares to a battery
with a capacity of 20%, which is capable of delivering only 12 consecutive 360
joule shocks. CONCLUSIONS: While manufacturers' recommendations on battery
replacement always have been based on an assumed technical threshold, these
recommendations are not based on individual battery performance. The system for
testing batteries described in this paper, should provide significant cost
savings and improve quality assurance within a prehospital AED program.
PMID- 10186997
TI - Stress levels in EMS personnel: a national survey.
AB - OBJECTIVE: The purpose of this study was to evaluate stress levels in emergency
medical services personnel across the United States. DESIGN: Confidential, 20
question survey tool, Medical Personnel Stress Survey--Abbreviated (MPSS-R). A
total score of 50 indicates average stress levels. A score of 12.5 on the subset
measurements of somatic distress, job dissatisfaction, organizational stress, and
negative attitudes towards patients indicates average levels of stress. Data were
analyzed using ANOVA and t-test. INTERVENTIONS: None. RESULTS: A total of 658 of
3,000 emergency medical technicians (EMTs) (22%) completed the survey. The mean
value of 69.3 +/- 6.3 for the total stress scores was very high. Mean values for
the subset scores were: somatic distress = 19.6 +/- 3.3; organizational stress =
17.3 +/- 2.4; job dissatisfaction = 17.0 +/- 2.6; negative attitudes towards
patients = 15.5 +/- 2.3. Characteristics predicting higher stress were EMT-basic
(A) licensure, basic life support (BLS) only service provider, volunteer status,
new employee working in a small EMS organization, and providing service to a
small town. CONCLUSION: Stress levels in EMS personnel were very high, were
manifested primarily as somatic distress, secondarily as organizational stress
and job dissatisfaction, and lastly as negative patient attitudes. Stress levels
and subset manifestations of occupational stress among EMS personnel varied
depending on gender, marital status, age, level of training and function, on
salaried or volunteer status, length of time as an EMT, and size of the
organization, city, and population served. Care should be taken to address
stresses peculiar to individual EMS system needs.
PMID- 10186998
TI - Paramedic interpretation of prehospital lead-II ST-segments.
AB - OBJECTIVE: To determine the reliability of ST-segment interpretation by
paramedics from lead-II rhythm strips obtained in the prehospital setting.
DESIGN: Prospective, blinded study of 127 patients transported by an urban/rural
emergency medical services system with complaints consistent with ischemic heart
disease. METHODS: Emergency department physicians asked emergency medical
technician-paramedics (EMT-P) via radio to evaluate ST-segments for elevation or
depression and grade it as "mild," "moderate," or "severe." Then, this rhythm
strip was interpreted blindly by emergency physicians who also interpreted the
lead-II obtained from a 12-lead electrocardiogram (ECG) obtained in the emergency
department (ED). The field interpretation was compared with the subsequent
readings and the final in-patient diagnosis using positive predictive value
(PPV), negative predictive value (NPV), and the Kappa statistic. Markedly
discrepant interpretations were analyzed separately. RESULTS: Using physician
interpretation as the reference standard, paramedic interpretation of the lead-II
ST-segments obtained in the prehospital setting was correct (within +/- 1
gradation) in 113 out of 127 total cases (89%). Of 105 patients for whom final
hospital diagnosis was available, the ST-segment on the rhythm strip obtained in
the prehospital setting, had a positive predictive value of 74% and a negative
predictive value of 85% for myocardial ischemia or myocardial infarction (MI) (p
< 0.001, Kappa = 0.59). Discordant interpretations between the paramedics and
emergency physicians often were related to a basic misunderstanding of rhythm
strip morphology. CONCLUSION: Field interpretation of ST-segments by paramedics
is fairly accurate as judged both by emergency physicians and correlation with
final patient outcome, but its clinical utility is unproved. A small but
clinically significant number of outliers, consisting of markedly discrepant
false positives, reflects paramedic uncertainty in identifying the deviations of
the ST-segment.
PMID- 10186999
TI - Feedback to emergency medical services providers: the good, the bad, and the
ignored.
AB - HYPOTHESIS: To determine the type and frequency of immediate unsolicited feedback
received by emergency medical service (EMS) providers from patients or their
family members and emergency department (ED) personnel. METHODS: Prospective,
observational study of 69 emergency medical services providers in an urban
emergency medical service system and 12 metropolitan emergency departments.
Feedback was rated by two medical student observers using a prospectively devised
original scale. RESULTS: In 295 encounters with patients or family, feedback was
rated as follows: 1) none in 224 (76%); 2) positive in 51 (17%); 3) negative in
19 (6%); and 4) mixed in one (< 1%). Feedback from 254 encounters with emergency
department personnel was rated as: 1) none in 185 (73%); 2) positive in 46 (18%);
3) negative in 21 (8%); and 4) mixed in 2 (1%). Patients who had consumed alcohol
were more likely to give negative feedback than were patients who had not
consumed alcohol. Feedback from emergency department personnel occurred more
often when the emergency medical service provider considered the patient to be
critically ill. CONCLUSIONS: The two groups provided feedback to emergency
medical service providers in approximately one quarter of the calls. When
feedback was provided, it was positive more than twice as often as it was
negative. Emergency physicians should give regular and constructive feedback to
emergency medical services providers more often than currently is the case.
PMID- 10187000
TI - Sonomatic confirmation of tracheal intubation using the SCOTI.
AB - This study compares the performance of two commercially available devices (Ambu
TubeChek and SCOTI) in establishing endotracheal (ET) tube position (oesophageal
vs. tracheal) in a mannequin and in miniature pigs. The Ambu TubeChek is a
syringe-type, Oesophageal Detector Device (ODD) that fits to the endotracheal
tube connector. Air is aspirated easily from the rigid trachea, but not from the
collapsing esophagus. The Sonomatic Confirmation of Tracheal Intubation device
(SCOTI) is a lightweight battery-powered, sonomatic device. It emits sound waves
into the tube and analyzes the reflection. The SCOTI purports to enable a user
independent and carbon-dioxide-independent assessment of tube position following
intubation. Intubation followed by tube position assessment with Ambu TubeChek
(ODD) was significantly faster and easier with the ODD than with the SCOTI. The
SCOTI cannot differentiate tracheal from oesophageal ET-tube position in mini
pigs. In situations in which capnometry is not available or the CO2 production
and transport are compromised (CPR), we recommend the use of an Oesophageal
Detector Device (ODD) rather than the SOCTI.
PMID- 10187001
TI - An eight-year review of legal cases related to an urban 9-1-1 paramedic service.
AB - INTRODUCTION: An eight year retrospective analysis was conducted to determine the
type and outcome of lawsuits related to the provision of 9-1-1 paramedic service
in an urban environment. METHODS: For the evaluation period of May 1986 to March
1994, all litigation cases related to Ambulance Service or paramedics were
collected and analyzed. This urban 9-1-1 Paramedic Service has an estimated call
volume of > 60,000 assignments resulting in > 30,000 patient encounters during
the evaluation period. RESULTS: Seven lawsuits were filed against the service. No
lawsuits were related to tardy response, failure to transport, or patient care
negligence of any kind. All of the litigation was related to motor vehicle
collisions (MVC). CONCLUSIONS: The data suggest that motor vehicle collisions are
a significant medical-legal risk to the EMS community. In addition, it was found
that the use and lack of use of seatbelts was an important component in many of
the suits.
PMID- 10187002
TI - Evaluation of intravenous tramadol for use in the prehospital situation by
ambulance paramedics.
AB - INTRODUCTION: An evaluation of the opioid analgesic tramadol (Zydol, Searle
United Kingdom) was carried-out by ambulance paramedics to assess its efficacy in
providing pain relief in the prehospital situation. METHOD: Type of subjects-
Patients suffering severe pain from any cause uncontrolled by other simple
methods. Number of subjects--101 patients received tramadol and 41 patients
served as a control. Study design--Random, open study. Statistical tests--Pain
score at scene and on arrival at hospital were compared using Fisher's exact
tests (2 sides). Logistic regression analyses also were applied to other factors.
RESULTS: Pain scores improved for 93.1% of the tramadol treated patients and for
44.0% of the controls. A total of 30.7% of patients treated with tramadol
complained of nausea after treatment compared with 17.1% before treatment and
with 12.2% of the control patients. CONCLUSIONS: Pain was significantly decreased
by the administration of tramadol. It was safe with only minimal side effects,
the major one being nausea. Suggestions are made for areas of further study.
PMID- 10187003
TI - Prehospital treatment of patients with i.v. heroin overdose: what are we
treating?
AB - OBJECTIVE: To measure blood levels of morphine and additional drugs in patients
suspected of intravenous (i.v.) heroin abuse and to evaluate the effects of
antidote treatment. DESIGN: Prehospital blood sampling in 52 patients. RESULTS:
Forty-five patients were blood-positive for heroin, eight of whom were
hospitalized. Forty-one patients also had abused additional drugs: minor
tranquilizers, ethanol, amphetamine, cocaine, and/or carbamazepine. Seven
patients had taken either only methadone or ketobemidione: one was admitted.
Treatment with increasing doses of naloxone indicated a necessity for
hospitalization. Six of 14 patients treated with naloxone (1.8 mg were
hospitalized. Seven patients had an extremely high blood level of morphine (0.2
mg/kg), that could be reverted with naloxone in moderate doses. CONCLUSION: This
study indicates that under prehospital conditions, it is difficult to identify a
patient intoxicated only with intravenous heroin. Nearly all patients treated
were cases of multiple drug/alcohol overdoses. Even the symptoms associated with
extremely high blood levels of morphine could be reversed with naloxone in
moderate doses.
PMID- 10187004
TI - Medical relief mission to Bosnia/Hercegovina: a case report.
AB - World attention has been focused on Bosnia/Hercegovina, where war erupted in
1992. The regional hospital of Mostar, an industrial city with a population of
100,000, operated with chronic shortages of medical supplies including general
anesthetic agents. In February 1992, just prior to the referendum for
independence in that republic, a shipment of medical supplies with anesthesics,
food, and clothing was delivered safely to Ljubuski, a village near Mostar, for
Mostar hospital and surrounding clinics by a small, private organization from
Birmingham, Alabama. No difficulties were encountered in delivering the supplies
despite warnings from the U.S. State Department, the lengthy transit from Austria
through Croatia to Bosnia, an active black market, and the inexperience of the
relief agency. This disaster relief effort by a small, private sponsor was
representative of both the positive aspects of such a project, as well as typical
negative aspects. These efforts had been discouraged in the past, but as disaster
medicine matures, there may be room for such endeavors, if properly directed.
PMID- 10187006
TI - One giant step for humankind.
PMID- 10187005
TI - The utilization of bicycles in the delivery of emergency medical services: a
preliminary report.
AB - INTRODUCTION: Bicycles may be useful in the delivery of out-of-hospital emergency
medical services. The use of bicycles in providing emergency medical services was
investigated by surveying currently existing bicycle-medic systems. METHODS: Two
questionnaires were developed to gain information on service areas, injuries,
gear used, missions, and specific data from bicycle-medic response. RESULTS: Of
210 surveys mailed to bicycle-medics, 21 (10%) were completed and returned by the
pre-established deadline. Of 11 surveys mailed to bicycle-medic supervisors, four
(36%) were returned. Preliminary results showed that 76% of respondents are
career providers and the remainder serve as volunteers. Mean age for respondents
was 33 +/- 7.4 years, with 96% being males. Most teams have been in existence for
three to four years. Job satisfaction was greater when participating on the
bicycle crews than when not performing on the bicycle crew, t = 4.15, p = 0.0002.
The teams varied in size (6-100 persons) with a mean value of 31. On the average,
team size represented 10% of total number of personnel for the respective
organizations. The majority of bicycle teams operate all year in all conditions.
Most bicycle-medic teams were initiated for special events. Nineteen percent
reported injuries while on duty or in training. Ninety percent of units that
responded use existing agency protocols and have no special protocols related to
the bicycle team. Eighty percent of the units are dispatched through the normal
agency procedures. Eighty-five percent of respondents coordinate for transport
units via dispatch. Reported response times were under two minutes for special
event responses. These were within established agency response times. In
approximately 25% of the responses, the patients refused transport, and another
65% of the responses were for relatively minor injuries or complaints that did
not require transport to a hospital. CONCLUSION: This survey begins to
characterize the utilization of bicycles as a tool to gain patient access in
specialized situations. The use of bicycle-medics may be cost-effective, may help
to improve employee morale, and possibly reduce employee health-care costs.
Further study is needed to determine the impact of bicycle-medics on patient
outcomes and response times.
PMID- 10187007
TI - The EMS response to the Oklahoma City bombing.
AB - This is a descriptive study of the Emergency Medical Services response to a
bombing of a United States Federal Building in Oklahoma City, Oklahoma on 19
April 1995. The explosion emanated from a rented truck parked in the front of the
building. The force of the explosion destroyed three of the four support columns
in the front of the building and resulted in a pancaking effect of the upper
floors onto the lower floors. There were three distinct phases of the medical
response: 1) Immediately available local EMS ambulances and staff; 2) Additional
ambulances staffed by recalled, off-duty personnel; and 3) mutual-aid ambulances
and personnel from the surrounding communities. There were 361 persons in the
building at the time of the explosion, 163 of these perished. Within the first
hour of the explosion, 139 patients were transported to area hospitals. Of these,
32% were in critical condition. During the day of the explosion, 444 persons were
treated for physical injuries: 410 of these were related to the explosion and 14,
including one with fatal injuries, were sustained during search and rescue
attempts. A total of 354 (80%) were treated and released from emergency
departments, and 90 (20%) were admitted to hospitals. Six of the transported
victims either were dead on arrival to the emergency department or died after
admission to the hospital. Of those who died, 95% of the deaths were related to
blunt trauma associated with the collapse of the structure. Only three persons
were extricated alive after the first five hours following the explosion. The
scene became flooded with volunteers who, although their intentions were to
provide help and aid to those injured, created a substantial logistical problem
for Incident Command. Several other lessons were learned: 1) Telephone lines and
cells became overloaded, but the Hospital Emergency Administrative Radio system
was operational only in three of the 15 hospitals; 2) Volunteer personnel should
have responded to the hospitals and not to the scene; and 3) Training was an
essential for the success of such a response. Thus, the success of this operation
was a function of the intense training, practice, and coordination between
multiple agencies.
PMID- 10187008
TI - How to cope with a visit from the Pope.
AB - A mass gathering always presents a challenge to the medical providers of a city
since preparations must be made to cover any potential disasters, big or small.
With a prediction of several hundred thousand people coming to the New York City
area to participate in the Papal Masses, the New York City-Emergency Medical
Services readied its forces of physicians, paramedics, and emergency medical
technicians from throughout the region. Extensive multi-agency planning involving
a Total Quality Management process was integral to the success of covering the
events.
PMID- 10187009
TI - Constructing a World Wide Web site for disaster management and humanitarian
assistance.
AB - There is a huge need for access to information in the areas of disaster relief,
disaster medicine, and humanitarian assistance. The extraordinarily rapid
increase in the literature in these subject areas attests to this need. However,
use of the printed word has substantial limitations that are even more profound
in the developing world. Currently, the information available tends to be
fragmented and sequestered by the specific interests of the organizations and
governments involved. The evolving electronic methods for the storage,
organization, and retrieval of information makes coordination between
organizations concerned with disasters within our grasp. This paper discusses the
Center of Excellence in Disaster Management and Humanitarian Assistance and
describes the World Wide Web and the implications it has in disaster management
and medicine. It describes methods for obtaining user input to the techniques
used for the development of the world wide web for the areas of disaster
management and disaster medicine. The implementation of an on-line Internet
reference desk that will provide: 1) a list of "experts;" 2) a searchable
disaster database; and 3) on-line simulation courses and training exercises also
is discussed.
PMID- 10187011
TI - 10th World Congress on Disaster and Emergency Medicine. Mainz, Germany, 26-27
September 1997. Abstracts.
PMID- 10187010
TI - The efficacy of integrating "smart simulated casualties" in hospital disaster
drills.
AB - INTRODUCTION: Full-scale disaster drills are complex, expensive, and may involve
hundreds or thousands of people. However, even when carefully planned, they often
fail to manifest the details of medical care given to the casualties during the
drill. OBJECTIVE: To assess the feasibility of integrating physicians among the
simulated casualties of a hospital disaster drill. METHODS: A total of 178
physicians graduating an Advanced Trauma Life Support (ATLS) course participated
in eight hospital disaster drills during 1994 as "Smart Victims." The
participants were given cards with descriptions of their injury and detailed
instructions on how to manipulate their medical condition according to the
medical care provided in the hospital. They also were given coded questionnaires
to fill out during the process of the drill. Conclusions were drawn from analysis
of the questionnaires and from a roundtable discussion following each drill.
RESULTS: The "smart casualties" made comments on the following topics: 1) triage
(over-triage in 9%, and under-triage in 4%); 2) treatment sites; 3) medical
equipment usage (i.e., shortage of ventilators and splinting devices); 4) medical
knowledge and care rendered by the hospital staff; 5) evacuation and escorting of
the wounded; 6) management of patients with post-traumatic stress disorder; and
7) medical documentation. Their comments contributed valuable information on the
quality of medical care and organization, and identified obstacles that otherwise
would have been overlooked. The "smart casualties" were very cooperative and
indicated that their participation in the drill contributed to their
understanding of disaster situations in hospitals. CONCLUSION: Integrating
physicians among the simulated casualties in a hospital disaster drill may
contribute to achieving the objectives of hospital disaster drills and add to
disaster management education of the simulated casualty physicians.
PMID- 10187012
TI - Primary health care in war and disaster and the NorAid system.
AB - When the infrastructure in a community is destroyed by manmade or natural
disaster, even the simplest health services may be difficult to maintain. By the
Alma Ata declaration, the World Health Organization (WHO) proclaimed, "Health for
all by the year 2000." The program is designed to cover the basic health needs as
defined by the Primary Health Care (PHC) system. Therefore, a most important
issue in a disaster, is to support, maintain, and rebuild the PHC system, to
secure the population's basic health services. Relevant and rapid aid is of great
importance in disaster. The physical and psychological strain caused by disaster
will increase the need for medical care compared to that during normal times.
Child mortality and maternal complications will rise, Many of the 12 million
children, who die every year, die as a result of war, refugee conditions, and/or
other types of disaster. The NorAid system is equipment composed to provide PHC,
with special emphasis on vulnerable groups e.g., women and children. Provided the
medical skills are available, it also may function as a hospital. The system
already has been used in many countries, and has been found to be relevant,
practical, and relatively cheap compared to the benefits achieved.
PMID- 10187013
TI - Medical outreach after hurricane Marilyn.
AB - INTRODUCTION: Many geographical areas are subject to devastating disasters that
leave the citizens not only without homes, but also without their local medical
systems. Now medical-aid stations consisting of personnel, supplies, and
equipment quickly can be deployed when needed to such areas under the aegis of
the National Disaster Medical System (NDMS). Such teams can provide emergent
medical care as well as daily medical care. However, these aid stations are of no
help for the home-bound or nursing home patients too infirm to reach them. Thus,
these citizens only can obtain medical care if medical teams make planned
outreach excursions to reach them. OBJECTIVE: To describe a planned outreach
program that was implemented for such patients on St. Thomas Island after it was
devastated by Hurricane Marilyn in 1995. RESULTS: Over a five-day period, the
outreach team provided medical care for 67 patients ranging in age from 11 days
to 90 years. Play and art therapy was provided for non-injured children. The most
common needs in the elderly were anti-hypertensive medications and insulin-loaded
syringes. CONCLUSIONS: For outreach efforts of this nature, membership of the
team should include a registered nurse, a paramedic, a respiratory therapist, a
public health specialist, and a local authority familiar both with the area and
its inhabitants. A physician does not need to be assigned to the team, but should
be available by radio.
PMID- 10187014
TI - Prehospital severity scoring at major rock concert events.
AB - INTRODUCTION: Rock and contemporary music concerts are popular, recurrent events
requiring on-site medical staffing. STUDY OBJECTIVE: To describe a novel severity
score used to stratify the level of acuity of patients presenting to first-aid
stations at these events. METHODS: Retrospective review of charts generated at
the first-aid stations of five major rock concerts within a 60,000 spectator
capacity, outdoor, professional sports stadium. Participants included all concert
patrons presenting to the stadium's first-aid stations as patients. Data were
collected on patient demographics, history of drug or ethanol usage while at the
concert event, first-aid station time, treatment rendered, diagnosis, and
disposition. All patients evaluated were retrospectively assigned a "DRUG-ROCK"
Injury Severity Score (DRISS) to stratify their level of acuity. Individual
concert events and patient dispositions were compared statistically using chi
square, Fisher's exact, and the ANOVA Mean tests. RESULTS: Approximately 250,000
spectators attended the five concert events. First-aid stations evaluated 308
patients (utilization rate of 1.2 per 1,000 patrons). The most common diagnosis
was minor trauma (130; 42%), followed in frequency by ethanol/illicit drug
intoxication (98; 32%). The average time in the first-aid station was 23.5 +/-
22.5 minutes (+/- standard deviation; range: 5-150 minutes). Disposition of
patients included 100 (32.5%) who were treated and released; 98 (32%) were
transported by paramedics to emergency departments (EDs); and 110 (35.5%) signed
out against medical advise (AMA), refusing transport. The mean DRISS was 4.1 (+/-
2.65). Two-thirds (67%) of the study population were ranked as mild by DRISS
criteria (score = 1-4), with 27% rated as moderate (score = 5-9), and 6% severe
(score > 10). The average of severity scores was highest (6.5) for patients
transported to hospitals, and statistically different from the scores of the
average of the treated and released and AMA groups (p < 0.005). CONCLUSION: The
DRISS was useful in stratifying the acuity level of this patient population. This
severity score may serve as a potential triage mechanism for future mass
gatherings such as rock concerts.
PMID- 10187015
TI - Quality management tool for mass casualty emergency responses and disasters.
AB - INTRODUCTION AND BACKGROUND: Quality management (QM) principles generally have
not been applied to multi-casualty and disaster situations. Quality management
incorporates quality assurance (QA) and quality improvement (QI) supported by a
management information system (MIS). Since responders to disasters and multi
casualty incidents generally operate on standing orders and/or protocols, the
character of the responses lends itself to quality management methods. Standards
and indicators of performance readily can be developed for these situations.
OBJECTIVES: 1) to format disaster medical records as data collection instruments;
2) to develop appropriate tools that are easy to use for rapid assessments; 3) to
develop a mechanism for determination of causes of injuries; and 4) to develop
methods to: a) track patients; b) document response and recovery; and c) document
the circumstances associated with the event. METHODS: Model tools using
checklists and short, fill-in answers are provided. These tools are designed to
be incorporated into the trauma or EMS registries. Emergency medical technicians,
nurses, physicians, and medical students scored the same disaster scenario for
the functional areas of calling the state of the disaster, triage, and field
stabilization. RESULTS: Testing indicated that the checklists are completed in
less than one minute, and produce objective data per patient in each functional
area evaluated. In one instance, data were compiled for 38 patients from one bus
accident in less than 10 minutes. The same data were reproduced, without
variation, in the same amount of time, by three different providers of varied
professional backgrounds.
PMID- 10187016
TI - Survey of Iowa emergency medical services on the effects of the 1993 floods.
AB - INTRODUCTION: From June through August 1993, extensive flooding in the
Mississippi and Missouri River basins resulted in 50 deaths and 12 billion
dollars [U.S.] in damages in nine Midwestern states. In Iowa (1990 population
2,777,000), the government declared all 99 counties Federal Disaster Areas. This
study examines how this event impacted local emergency medical services (EMS).
METHODS: All 797 registered prehospital ambulance, rescue, and first-response
companies in Iowa received survey questionnaires. Two follow-up mailings were
provided for non-responders. RESULTS: A total of 468 EMS companies (59%) returned
completed questionnaires. The geographic distribution of responders and non
responders was similar. Of the companies responding, 132 (28%) reported an impact
on their operations from the flood disaster. The most frequently reported
operational changes included the use of non-traditional vehicles, providing aid
to regions outside usual service areas, and involvement in non-medical rescue
operations. CONCLUSION: A major flood provides unique challenges for emergency
medical services. Cross-sectional surveys can identify areas of improvement for
prehospital systems located in flood-prone areas. Results from this study provide
a basis for constructing a more refined instrument to study future flood
disasters.
PMID- 10187017
TI - Assessment of a scenario-based approach to facilitating critical thinking among
paramedic students.
AB - INTRODUCTION: Paramedic practice is shifting from [direct] on-line medical
control to protocol-driven care initiated on the paramedic's judgment of the
patient's problem(s). Teaching in most paramedic training programs remains
grounded in technical rationality. This does not adequately prepare practitioners
for current day practice. Medical conditions often present as ill-defined
problems. To deal with these situations, practitioners need problem solving and
reflective-thinking skills. Methodologies incorporating the use of these skills
in a contextual situation similar to actual practice may help paramedics develop
these skills. HYPOTHESIS: This study sought to determine the impact of written
scenario exercises in the context of clinical problems as a means of learning in
order to foster higher level thinking skills and self-directed tendencies. It
involved three hypotheses: 1) Post-test scores would correlate with scores
attained on the traditional, multiple choice, final examination; 2) Post-test
scores would correlate with scores on the critical thinking sub-test of the final
examination; and 3) Scores would be better on the post-test compared to the pre
test. METHODS: This two year, longitudinal, prospective study was conducted with
55 paramedic students using a pre- and post-test. Post-test scores were compared
with final examination scores and scores of the subset of higher level thinking
questions within that examination using the Pearson r-test. The relationship
between the pre- and post-test scores was analyzed using a one-tailed dependent t
test. Post-hoc analysis of the variables of age, experience, and education was
conducted using one-way analysis of variance. RESULTS: The correlation between
post-test scores with final examination scores was positive and modestly
significant. There was no correlation of post-test scores with sub-test scores.
Comparison of pre- and post-test scores was significant. Effects for age,
experience, and education were not significant statistically. CONCLUSIONS: Using
written scenarios increases ability to utilize reflective thinking and self
directed tendencies. However, this ability may not be demonstrated consistently
on traditional written examinations. A multi-site study using large numbers and a
control group or alternative methods appears to be indicated to demonstrate more
accurate effects of the methodology.
PMID- 10187018
TI - Epidemiologic assessment of mortality, building collapse pattern, and medical
response after the 1992 earthquake in Turkey. Disaster Reanimatology Study Group
(DRSG).
AB - BACKGROUND: Post-earthquake engineering and epidemiologic assessments are
important for the development of injury prevention strategies. This paper
describes mortality and its relationship to building collapse patterns and
initial medical responses following the 1992 earthquake in Erzincan, Turkey.
METHODS: The study consisted of: 1) background data collection and review; 2)
design and implementation of a field survey; and 3) site inspection of building
collapse patterns. The survey included: 1) national (n = 11) and local (n = 17)
officials; 2) medical and search and rescue (SAR) workers (n = 38); and 3) a
geographically stratified random sample of lay survivors (n = 105). The survey
instruments were designed to gather information regarding location, injuries,
initial actions and prior training of survivors and responders, and the location,
injuries, and management of dead and dying victims. A case-control design was
constructed to assess the relationship between mortality, location, and building
collapse pattern. RESULTS: There was extensive structural damage throughout the
region, especially in the city where mid-rise, unreinforced masonry buildings
(MUMBs) incorporating a "soft" first floor design (large store windows for
commercial use) and one story adobe structures were most vulnerable to collapse.
Of 526 people who died in the city, 87% (n = 456) were indoors at the time of the
earthquake. Of these, 92% (n = 418) died in MUMBs. Of 54 witnessed deaths, 55% (n
= 28) of victims died slowly, the majority of whom (n = 26) were pinned or
trapped (p < 0.05). Of 42 MUMB occupants identified through the survey, those who
died (n = 25) were more likely to have been occupying the ground floor when
compared with survivors (n = 28) (p < 0.01). Official medical and search and
rescue responders arrived after most deaths had occurred. Prior first-aid or
rescue training of lay, uninjured survivors was associated with a higher
likelihood of rescuing and resuscitating others (p < 0.001). CONCLUSIONS: During
an earthquake, MUMBs with soft ground floor construction are highly lethal,
especially for occupants on the the ground floor, suggesting that this building
type is inappropriate for areas of seismic risk. The vulnerability of MUMBs
appears due to a lack of lateral force resistance as a result of the use of glass
store front windows and the absence of shear walls. The prevalence of this
building type in earthquake-prone regions needs to be investigated further. A
large portion of victims dying in an earthquake die slowly at the scene of
injury. Prior public first-aid and rescue training programs increase
participation in rescue efforts in major earthquakes and may improve survival.
PMID- 10187019
TI - Interactive computer-aided training of emergency care tactics: an experimental
study with medical students.
AB - INTRODUCTION: It is important to know which level of tactical preparedness is
reached after completing lectures and training included in a medical curriculum.
A computer-based interactive programme aimed for tactical training of emergency
care tactics at the scene (Matimed, Matimed Ltd, Kuopio, Finland) was used in
testing the skills of 20 medical students. METHOD: In this standardised test,
every student first received guided introduction on the technical use of the
programme. The test included four severely injured victims. The traumas used were
hepatic rupture, flail chest, haemothorax, and femoral fracture. The students
were tested in making decisions on the priority of care and transportation and in
keeping the patients alive with appropriate emergency care until they were
transported to a trauma centre. RESULTS: Only five of 20 (25%) succeeded in this
task, 50% lost one victim and 25% lost two. The results show that the tactical
preparedness of medical students is far from what is presumed. A more detailed
analysis shows serious deficiencies in decision-making, priority order of
actions, and in the use of available resources. CONCLUSIONS: This type of
interactive computer-aided training of tactics appropriately supplements
theoretical lectures, and partially fills the need for practical training.
PMID- 10187020
TI - Adenosine for the treatment of PSVT in the prehospital arena: efficacy of an
initial 6 mg dosing regimen.
AB - OBJECTIVE: To confirm the efficacy of prehospital administration of adenosine,
using a 6 milligram (mg) initial dosing regimen, for the treatment of paroxysmal
supraventricular tachycardia (PSVT). METHODS: Urban, suburban, rural emergency
medical services (EMS) system in Clark County, Washington with advanced life
support (ALS) patient transports. Concurrent, paramedic Medical Incident Report
(MIR) review was conducted for 102 patients receiving prehospital adenosine
during a 42-month period. Patients were administered 6 mg of adenosine using an
intravenous (i.v.) bolus followed by 10 ml of balanced salt solution flush. If
the patient's rhythm remained unchanged, the dosing regimen was increased to 12
mg followed by a 10 ml flush. This was repeated once more if the rhythm remained
unchanged, to a total maximum dose of 30 mg. Medical direction for administration
of adenosine was in the form of standing orders rather than direct (on-line)
medical control. RESULTS: Seventy-four of 102 patients had PSVT as determined by
physician analysis of the initial six-second electrocardiographic rhythm strip
(ECG) recording. Sixty-six of these patients converted their cardiac rhythm from
PSVT using adenosine; 46 (70%) converted with the initial 6 mg bolus. Fifteen
patients converted after receiving the second dose (12 mg); and five patients
required 30 mg. CONCLUSION: These results show that for paramedics, adenosine is
an effective treatment for PSVT. An initial bolus of 6 mg converts the majority
of cases. Eighty-nine percent of cases of confirmed PSVT converted with adenosine
administration.
PMID- 10187021
TI - Health crisis and the Internet: harnessing the power of the Internet for
disasters and epidemics. Pan American Health Organization.
PMID- 10187022
TI - Airborne field hospital in disaster area: lessons from Armenia (1988) and Rwanda
(1994).
AB - The outcome of survivors within disaster areas largely depends upon the quick
reallocation and operation of logistic and medical support systems. Enthusiastic
media equipped with advanced communication systems, reveal mass human suffering
in real time. But, the response period required for the organization of rescue
systems is much slower and is most frustrating. In this article, we present our
experience in quick deployment and operation of airborne field hospitals gained
following the earthquake disaster in Armenia in 1988 and the civil war in Rwanda
in 1994. Deployment of improvised, volunteer-based, military field hospitals was
feasible within 24 hours after the decision was made. A multi-disciplinary
structure enabled an effective, flexible mode of operation and reduced the
dependency on mericulous, time-consuming assessments of requirements prior to
deployment. These missions are a paradigm for the successful incorporation and
integration within the capabilities of military infrastructure of volunteer
professionals drafted from civil medical facilities. Such field hospitals could
provide backup for primary care medical systems in disaster areas and substitute
or take some pressure off of local hospitals, particularly when evacuation
systems are insufficient.
PMID- 10187023
TI - Hospital disaster management simulation system.
AB - INTRODUCTION: Theoretically, simulation of disastrous situations has many
advantages in that it prepares hospital staff to cope with the real scenario. It
is a challenge to create the database and custom-making a friendly software while
still keeping it representative of a real situation. This article describes
experience with developing and implementing the use of simulation software as a
drilling technique used by Israeli hospitals. METHODS: The application was
developed using SIMAN/ARENA software. Knowledge and a database for a basic multi
casualty incident (MCI) were developed in the pilot phase. It contains detailed
descriptions of the casualties which can be compared with the real hospital
capabilities (staff and infrastructure). A consensus committee decided the
crucial model issues and established the thresholds for quality performance
indicators. Interfaces to the each hospital's information management systems
(IMS) were developed and the various output documents of each exercised step were
updated. Before drilling, the hospital managerial staff received notice and had
to prepare the data on the anticipated resources required. The simulation staff,
as well as representatives from the hospitals, then conducted the limited scale
drill (LSD). RESULTS: During the LSD, the trained hospital staff were given two
types of input: 1) copies of reports on patients entering the stations and had to
enter them into its IMS; and 2) timed telephone notifications of problems in each
station. During a 90 minutes drill, there were about 15 timely reports and 20
telephone problems. The evaluation of the LSD were based mainly on the following:
1) observing the staff solving various problems; 2) constructing a detailed
picture of the situation; and 3) measuring the effectiveness of the hospital IMS.
The drill ended with a discussion. Lessons are drawn from each drill in order to
find methods for optimizing the conduct of the hospital. An animation tool proved
to be useful in describing bottle necks in emergency room, diagnostic department,
and operating rooms. CONCLUSIONS: Simulation techniques and a preparatory limited
scale drill have advantages in evaluating and improving preparedness of hospitals
for managing an MCI before a full scale drill is carried out.
PMID- 10187024
TI - Emergency medical services in the reconstruction phase following a major
earthquake: a case study of the 1988 Armenia earthquake.
AB - STUDY OBJECTIVE: To use the clinical activities of an ambulance service as a tool
to assess the residual and unmet medical needs of a city in the aftermath of a
major earthquake and to apply that assessment to the development of a training
curriculum for the prehospital personnel. METHODS: The researchers conducted
structured interviews with health care workers at all levels of the emergency
health care delivery system in Gyumrii, Armenia, and carried out a retrospective
frequency analysis of 29,010 ambulance runs for an 11-month period from February
through December 1992. Runs first were assigned into the broad categories of: 1)
Adult Medical; 2) Pediatric Medical; or 3) Trauma, and then, according to
diagnosis. The runs then were classified further as: 1) Primary Care; 2) Basic
Life Support (BLS); or 3) Advanced Life Support (ALS). RESULTS: Adult Medical
calls represented 24,684 (85%), Pediatric Medical calls 459 (1.6%), and Trauma
calls 3,867 (13%). Only 12% of all ambulance calls resulted in transport to a
medical facility, although this percentage was higher in children. Thirty percent
of Adult Medical patients were diagnosed by the emergency medical providers as
having exclusively a psychiatric problem. CONCLUSION: In the late aftermath of a
devastating earthquake, the ambulance service in Gyumrii, Armenia has been
delivering a substantial proportion of non-emergency, primary care services. They
have adopted this unconventional role to compensate for the deficit in health
care facilities and personnel created by the disaster. The training program that
the investigators developed reflected the actual work activities of the
prehospital personnel demonstrated in their assessment.
PMID- 10187025
TI - Gender issues and partner preferences among a sample of emergency medical
technicians.
AB - INTRODUCTION: From its beginnings, the provision of emergency medical services in
the United States has been a male-dominated occupation. The objective of this
exploratory study was to determine if and how such issues might influence partner
preferences of male and female emergency medical technicians (EMTs). METHODS:
Initially, unstructured interviews were conducted with 10 EMS workers enrolled in
a paramedic training program in order to see whether and how such issues might
affect partner preferences. From the data obtained during these interviews, a
questionnaire was developed and distributed to participants in an annual meeting
of Louisiana Association of Nationally Registered EMTs. Participation was
voluntary and uncompensated. RESULTS: A total of 49 EMTs (22 women, 27 men)
completed the questionnaire. The major gender-related issues could be classified
into three dimensions: 1) physical strength; 2) assumption of authoritative
roles; and 3) structural (organizational) preparedness to implement gender-
friendly working environment. In general, the gender of a partner now "makes no
difference". CONCLUSIONS: Overall, the EMS work worlds are reflective of the
larger society of which they are a part. Now is the time for EMS systems to
examine the gendered nature of their organization and of the issues of gendered
expectations prevalent in EMS work. Future research should document the changes
now due in the field of emergency medical services.
PMID- 10187026
TI - An inventory of ambulance service regulatory programs in California.
AB - INTRODUCTION: Ambulance regulation in California is the responsibility of
numerous agencies on the state and local levels. OBJECTIVE: By identifying and
analyzing the variety of programs used in one state, this study establishes a
framework for evaluation of state and local regulatory programs elsewhere.
METHODS: This study surveyed all California local EMS agencies (LEMSAs:
California's equivalent of regional EMS organizations) to identify the types of
regulatory programs used, the foci of these programs (e.g., equipment and
personnel), and their application (e.g., public and private providers). All data
acquired were analyzed using population parameters rather than inferential
statistics. FINDINGS: A response rate of 100% was obtained. Among the regulatory
tools used are ordinances, contracts, and franchises. Regulatory standards vary
widely as do their applications. Large counties and those that operate their own
LEMSA have more extensive regulatory programs than do smaller counties and those
who participate in multicounty agencies. Many of the enforcement mechanisms
available are weak. CONCLUSION: This study suggests several policy implications
for California and other states. The wide variation in the types of regulatory
programs and the standards that are used suggest that the purpose and impact of
regulatory programs should be studied further. The decentralization of the
ambulance regulatory program and the lack of integration of ambulance regulations
into EMS system planning also raise policy questions. In addition, the role of
multicounty EMS agencies, as it relates to regulation of ambulance services,
should be reviewed.
PMID- 10187027
TI - Distribution of learning styles and preferences for learning environment
characteristics among Emergency Medical Care Assistants (EMCAs) in Ontario,
Canada.
AB - INTRODUCTION: In Ontario, Canada, Emergency Medical Care Assistants (EMCAs) have
many opportunities for continuing education. However, little is known about how
EMCAs learn. OBJECTIVES: The intent of this study was to explore the distribution
of learning styles, preferences for major learning environment characteristics,
and the associations between these two factors among the EMCA population in
Ontario, Canada. METHODS: Following review of the literature, a 32-item survey of
learning environment characteristics was constructed to measure the respondents'
preferences. Using a random number generator, 386 EMCAs were selected for
participation. Each received: a) an explanatory cover letter; b) a copy of the
Kolb Learning Style Inventory (LSI) questionnaire; c) a second questionnaire
consisting of learning environment characteristics; and d) a stamped, return
addressed envelope. Completed surveys were scored to determine the respondent's
Learning Style. The LSI and Learning Environment survey results were entered into
a data base and subjected to Dual Scaling analysis in order to 1) Identify the
distribution of learning styles; and 2) Explore associations between styles and
environmental characteristics. RESULTS: A total of 75 completed surveys were
returned, each of the four styles of learning (Converger; Diverger; Assimilator;
and Accommodator) were identified in the sample. Dual Scaling analysis indicated
a noteworthy association (R(jt) correlation > 0.300) between learning style and
10 of the 32 environmental characteristics. The data describe the usefulness of
each of the learning styles. Accommodators believed courses with a strong
emphasis on practical applications and working in groups to be very useful, but
were less interested in courses with a strong emphasis on theory. Assimilators
felt lectures and courses with a strong emphasis on theory very useful, but were
less interested in providing input into course objectives. Divergers found that a
lot of verbal explanation is useful, but were less interested in working with
teachers who act as coaches. Convergers believed that working with teachers who
act as coaches is useful. They also preferred courses with a strong emphasis on
practical applications, but were less interested in courses with a strong
emphasis on theory. CONCLUSIONS: The findings in this study, provide some
additional insight into the connections between learning style and elements of
the learning environment, and their application may contribute to
operationalizing learning theory.
PMID- 10187028
TI - The cadre of death education instructors in paramedic programs.
AB - OBJECTIVE: This study addresses the paucity of literature on death education
offerings in emergency medical services schools. The study examines the cadre of
death education instructors in paramedic training programs. Examining death
education offerings in paramedic programs can provide insight into how well
emergency medical services personnel are prepared when encountering bereaved
persons on death-related responses. METHODS: In an exploratory study, information
was gathered from paramedic programs on the instructors who teach death-related
education. A self-administered survey was sent to each (n = 537) paramedic
programs in the USA. The survey solicited the number of instructors teaching
death education, their backgrounds, and their formal training in death-related
instruction. RESULTS: The response rate was 45.4%. The majority of programs (78%)
reported using a paramedic as the primary instructor to teach death-related
content. Nurses (66%) and physicians (32%) also were utilized frequently. More
than two-thirds (68%) of the responding programs utilize faculty members who have
had no formal training in death and dying. Only one-third of the programs
utilizes a multidisciplinary staff. Less than 40% of responding programs teach
all of their death-related curricula with instructors who are trained in death
education. CONCLUSION: This study indicates that the majority of paramedic
programs are not utilizing an instructor cadre that is formally trained in death
education, nor are they using a multidisciplinary staff. Reasons for using these
instructors to teach death education in paramedic programs are discussed.
PMID- 10187029
TI - The tale of the tragedy of Neftegorsk.
AB - An earthquake with a magnitude of 7.6 struck the town of Neftegorsk (population
about 3,000) on 27 May, 1995. This paper describes the devastation and the human
aspects of the catastrophe of the first week following the quake. A total of
1,995 persons were found dead under the rubble, including 268 children less than
16 years of age. There were 1,144 survivors. A total of 406 person were rescued
alive from under the rubble of which an additional 37 persons died in a hospital
following rescue. Most of the survivors have been relocated, but some remain in
the area. There remains a need for psychological support for the survivors and
rescuers.
PMID- 10187030
TI - Lung function during hoist rescue operations.
AB - INTRODUCTION: A case is presented in which a 43-year-old man suffering from a
severe asthma attack, had ventilatory arrest during a hoisting procedure. Based
on this experience, the influence of three hoisting techniques on lung function
was tested. METHODS: The ventilatory capacity of 12 healthy volunteers was tested
during three commonly used hoisting techniques: 1) single sling; 2) double sling;
or 3) strapped to a stretcher. RESULTS: The vital capacity (VC) and the one
second, forced expiratory volume (FEV1) were reduced significantly during all
hoisting techniques compared to the standing position. The reduction was
significantly more pronounced on a stretcher than in either sling position. There
were no differences in the FEV1 to VC ratio between the positions. CONCLUSION:
The small reduction in ventilatory capacity during hoisting procedures is
tolerated easily by healthy individuals, but should be taken into account when
planning such procedures on patients with severe pulmonary disease.
PMID- 10187031
TI - The efficacy of advanced life support: a review of the literature.
AB - INTRODUCTION: Jurisdictions throughout the United States and some other parts of
the world have invested substantial time and resources into creating and
sustaining a prehospital advanced life support (ALS) system without knowing
whether the efficacy of ALS-level care had been validated scientifically. In
recent years, it has become fashionable for speakers before large audiences to
declare that there is no scientific evidence for the clinical effectiveness of
ALS-level care in the out-of-hospital setting. This study was undertaken to
evaluate the evidence that pertains to the efficacy of ALS-level care in the
current scientific literature. METHODS: An extensive review of the available
literature was accomplished using computerized and manual means to identify all
applicable articles from 1966 to October, 1995. Selected articles were read,
abstracted, analyzed, and compiled. Each article also was categorized as
presenting evidence supporting or refuting the clinical efficacy of ALS-level
care, and a list was constructed that pointed to where the preponderance of the
evidence lies. RESULTS: Research in this field differs widely in terms of
methodological sophistication. Of the 51 articles reviewed, eight concluded that
ALS-level care is not any more effective than is basic life support, seven
concluded that it is effective in some applications but not for others, and the
remainder demonstrated effectiveness. The strongest support for ALS-level care
was in the area of responses to victims of cardiac arrest, whereas somewhat more
divergent findings related to trauma or non condition-specific studies.
CONCLUSIONS: While not unanimous, the predominant finding of recent research into
the clinical effectiveness of advanced life support demonstrates improved
effectiveness over basic life support for patients with certain pathologies. More
outcomes-based research is needed.
PMID- 10187032
TI - Principles of disaster management lesson 1: introduction.
PMID- 10187033
TI - Forging freedom from fear.
PMID- 10187034
TI - Consensus conference on platelet transfusion. Final statement.
PMID- 10187035
TI - Hepatitis C virus RNA testing by nested PCR in blood preparations in Yugoslavia.
AB - Patients receiving any kind of human blood preparations are in permanent danger
of any infection including hepatitis C (HCV) infection. Testing for the presence
of HCV in blood preparations is one of the steps towards safe medical treatment.
One of the approaches for this testing is a detection of HCV nucleic acid. In
this paper we describe a simple method for isolation of HCV RNA from blood
preparations and control of HCV RNA presence in 19 intravenous and intramuscular
products, manufactured in the National Blood Transfusion Institute in Belgrade.
RT-PCR was performed according the rules saving RNA. Primers were located in 5'
conserved region. Seven out of 19 batches of gamma-globulin, albumin, anti
tetanus and anti-rabies immunoglobulin preparations were found to be HCV RNA
positive. For the time being, the PCR method is too expensive for routine HCV RNA
testing of hundreds of blood donors per day. Serological screening test of blood
donors and nested PCR testing for HCV RNA in blood preparations could be an
efficient combination of tests in prevention of posttransfusion hepatitis C.
PMID- 10187036
TI - The blood bank and hepatitis G.
AB - HGV can be transmitted by transfusion and is capable of inducing persistent
infection. Thus far it appears to have no discernable disease association. We
determined the infection rate of HGV in volunteer blood donors and patient with
risk factors for viral transmission through the blood. The association between
HGV infection and exposure to labile blood products could be a problem for blood
banks in the future.
PMID- 10187037
TI - Computer assisted prospective review of blood product utilization: a large
hospital experience.
AB - In an effort to assess need to administer blood products, we developed a computer
assisted prospective blood utilization review system. Prior to transfusion,
clinical information (from the blood requisition form) and pertinent laboratory
data (from the laboratory information system) are checked against approved
hospital transfusion guidelines (HTG). If request-review is outside HTG, the
blood bank physician is called to review and consult with ordering physician. Of
27,840 requests received in a year period (1995-1996), 1.2% (327) were outside
HTG and were physician reviewed. The great majority, 120/160 (88%) of requests
for red blood cells (RBC) or whole blood were approved; about 65% of these were
approved in patients with cardiorespiratory dysfunction and hemoglobin (Hb) > or
= 90 g/L. Slightly more than two-thirds, 84/119 (71%) of platelet concentrate
requests reviewed were approved; about 69% of them were approved in patients who
were either bleeding or were undergoing an invasive procedure and had platelets >
or = 20 x 9/L. Almost four-fifths, 38/48 (79%) of fresh frozen plasma or
cryoprecipitate requests reviewed were approved; all in bleeding patients with
sepsis and/or disseminated intravascular coagulation. Based on the frequent
request for RBC transfusions in patients with cardiorespiratory dysfunction and
Hb > or = 90 g/L, we have obtained approval to increase the Hb threshold to < 130
g/L as a means of facilitating measures to increase oxygen delivery.
PMID- 10187038
TI - Plasmapheresis in myasthenia gravis. A survey.
AB - Plasmapheresis plays an important role in the acute management of patients with
severe myasthenia gravis. Although plasmapheresis is now in use for more than 20
years, some controversies remain about the indication and the place in the
therapy. It is generally found that the effect starts one week after the start of
PP and lasts about 2-4 weeks after the last exchange; because of this temporary
effect use of concomitant immunosuppressive medication is recommended.
Compilation of data from 13 large series shows that about 75% of the patients
react favourably. The relation between fluctuations of antibodies and the effect
of PP is poor; even seronegative patients may improve as well.
PMID- 10187039
TI - Surveillance for factor VIII inhibitor development in the Canadian Hemophilia A
population following the widespread introduction of recombinant factor VIII
replacement therapy.
AB - In the Fall of 1994 the majority of Canadian Hemophilia A (Factor VIII (F.VII)
deficiency) patients who were receiving replacement therapy were converted to
Recombinant Factor VIII (rF.VIII) from plasma derived products. This decision was
taken and funded by the Canadian Blood Agency following the advice of the
Association of Hemophilia Centre Directors of Canada (AHCDC) who considered this
to be the safest replacement therapy available. Although it was the considered
opinion of the AHCDC that there was no evidence available to support the
theoretical concern that rF.VIII may prove more immunogenic than plasma derived
products, patient follow up included intensive surveillance of all patients
converted for this complication. A central reference laboratory was established
and plasma specimens obtained before and 6-12 months following conversion to
rF.VIII were referred for evaluation for inhibitor development by the classical
Bethesda Assay. By concensus of the referring centers a Bethesda Unit
(BU)/activity of 0.5 or greater was considered to be clinically significant. No
increase in the incidence of inhibitor development has been recorded in 478
patients followed for one year after conversion. This pattern has not changed in
339 of these patients followed for a further year. Of interest was the finding by
the reference laboratory that 8.0% of patients had BU activity of 0.5 or greater
before conversion to rF.VIII. Many of these individuals lost this activity after
conversion to rF.VIII as did others who appeared to have developed inhibitory
activity during the first year of follow up but became inhibitor free in the
second year of therapy. Overall, the incidence of true inhibitor development,
i.e. negative pre-/positive post-conversion to rF.VIII, in this population of
Hemophilia A patients was 2-3% over 2 years. This is similar to the incidence in
patients treated with plasma derived products. These data emphasize the need for
rigorous baseline evaluation in such investigations and the heterogeneity of the
inhibitor response as assessed by in vitro assay. It was concluded that, although
no attempt was made to correlate these in vitro data with clinical observations
including F.VIII recovery and survival, the use of rF.VIII in hemophiliacs
previously treated with plasma derived products was not associated with an
increase in F.VIII inhibitor development.
PMID- 10187040
TI - Therapeutic cytokine stimulation of thrombocytopoiesis.
AB - Endogenous thrombopoietin (TPO) stimulates platelet production by inducing dose
dependent megakaryocyte development from early marrow hematopoietic progenitors
and subsequent proliferation and endoreduplication. Recombinant human (rHu) TPO
or pegylated recombinant human megakaryocyte growth and development factor (PEG
rHu MGDF) produce log-linear responses in experimental animals and humans when
administered over the dose range of 0.05-25 micrograms/kg/day with respect to
peak peripheral platelet counts (or peripheral platelet mass turnover) and marrow
megakaryocyte volume, ploidy, number and mass. Other cytokines stimulating
megakaryocytopoiesis in various species using different dosing regimens include
Interleukin 1 (IL-1), Interleukin 3 (IL-3), Interleukin 6 (IL-6), Interleukin 11
(IL-11), stem cell factor (SCF), granulocytemacrophage colony stimulating factor,
(GM-CSF), fusion proteins, such as promegapoietin, and a peptide agonist of TPO
receptor. Whereas neither rHuTPO nor PEG-rHuMGDF induce platelet aggregation in
vitro, they transiently enhance aggregatory responsiveness of platelets to
physiologic agonists from several different experimental animals both in vitro
and ex vivo. However, platelet recruitment into forming thrombus is not augmented
by these agents when evaluated in quantitative rabbit or baboon models of
platelet-dependent thrombus formation, except for the effect of platelet
concentration per se. These findings indicate that appropriate dosing of these
agents following marrow suppression prevents thrombocytopenia without increasing
the risk of platelet-dependent thrombo-occlusive complications.
PMID- 10187041
TI - Clinical use of recombinant FVIIa (rFVIIa).
AB - Haemostasis is initiated by the complex formed by TF and FVIIa present in the
blood (1% of the FVII protein). Recombinant FVIIa, which is active only after
having formed complex with TF exposed following tissue damage, has been
demonstrated to induce haemostasis in haemophilia patients with life- and limb
threatening bleedings with an efficacy rate of 76-84% in patients having failed
on other treatment. Several had proven septicaemia but only one patient developed
consumption coagulaopathy during extensive surgical manipulation and removal of
myonecrotic tissue. No antibody formation against FVII has been seen in
haemophilia patients. In 13 major surgical episodes complete intra- and post
operative haemostasis was achieved. rFVIIa has been used successfully in FVII
deficient patients and has been found to normalise the PT in patients with liver
disease and in warfarin treated individuals. Single patients with platelet
defects and with vWillebrand's disease type 3 achieved haemostasis with rFVIIa.
PMID- 10187043
TI - Stem cells: what's happening? Focus on quality assurance, GMP and regulatory
aspects.
PMID- 10187042
TI - Mammalian recombinant coagulation proteins: structure and function.
AB - Recombinant DNA technology has permitted the production of synthetic proteins
which are potentially free of human infectious agents. Despite production in
foreign cells, these proteins are structurally and functionally comparable to the
native proteins. Recombinant clotting factors VIII, IX, VIIa, and von Willebrand
factor have the same primary sequence as their plasma counterparts. The secondary
and tertiary structures are similar, Post-translational modifications, including
proteolytic processing, disulfide bonding, addition and processing of N- and O
linked glycans, gamma-carboxylation of glutamic acid residues, beta-hydroxylation
of aspartic acid residues, sulfation of tyrosine residues, and phosphorylation of
serine residues, are similar but not always identical, In some instances. these
differences may cause significant functional differences. For example, reduced
tyrosine sulfation and serine phosphorylation of recombinant factor IX have been
correlated with reduced recovery following intravenous infusion. The specific
clotting activity of the recombinant factors, an indication of their coagulant
function, is equivalent to that of the plasma factors. Finally, these proteins
have been used clinically and shown to correct clinical deficiencies of these
proteins in a manner that is similar to replacement with plasma factors. All in
all, the promise of recombinant DNA technology for coagulation and other
disorders remains bright.
PMID- 10187044
TI - Disabilities still hinder individuals' quality of life.
PMID- 10187045
TI - Foreign-trained PTs flunking US exam.
PMID- 10187046
TI - Out of the dark.
PMID- 10187047
TI - Moving forward.
PMID- 10187048
TI - Dealing with pain.
PMID- 10187049
TI - HER-2 breast assay, linked to Herceptin, wins FDA's okay.
PMID- 10187050
TI - It's sooner--or later--for blood substitutes.
PMID- 10187051
TI - Blood banks hail automation age.
PMID- 10187052
TI - Ready ... set ... wait....
PMID- 10187053
TI - FDA's efforts frazzling many in blood bank field.
PMID- 10187054
TI - Early prenatal screening matures.
PMID- 10187055
TI - No clear title to clinical data ownership.
PMID- 10187056
TI - DNA: the new judge and jury?
PMID- 10187057
TI - Nursing practitioners: growing competition for family physicians?
PMID- 10187058
TI - Disease management: who's caring for your patients?
PMID- 10187059
TI - In search of an effective physician compensation formula.
PMID- 10187060
TI - Emerging public policy demands broader public health planning.
PMID- 10187061
TI - Local health departments: planning for a changed role in the new health care
environment.
AB - Several reports have identified a series of public health planning tools that are
helpful but not sufficiently comprehensive for planning in the current health
care environment. This article describes the planning efforts of six local health
departments (LHDs) in Florida and the results. These suggested that the LHDs
would have benefited from using one of the approaches commonly found in the
private sector, strategic planning. A strategic planning framework for LHDs is
described and a series of relevant questions are suggested to aid in strategic
planning.
PMID- 10187062
TI - Preparing for the future in a local public health organization.
AB - One of the most difficult issues in strategic planning in public health
organizations is how to harness the energy generated in the process of strategic
thinking and focus it on strategy formulation. This article is about one local
public health organization's experience in developing program priorities,
building consensus about the priorities, and making operational the adaptive
strategies relative to each program. The results should be useful to all public
health organizations attempting to direct strategic thinking toward the
formulation of practical and motivational strategies for the future.
PMID- 10187063
TI - Core function-related local public health practice effectiveness.
AB - This article assesses the extent to which the U.S. population in 1995 was being
effectively served by public health's three core functions (assessment, policy
development, and assurance). A random sample of local health departments (LHDs)
stratified by population size and type of jurisdiction was asked to provide their
opinion of, as well as indicate performance on 20 core function-related measures
of local public health practice. The article concludes that, in 1995, the nation
fell far short of its year 2000 national objective, which called for 90 percent
of the population to be served by an LHD effectively carrying out public health's
core functions. Considerable capacity building and performance improvement is
needed within the public health system.
PMID- 10187064
TI - Steps to changing state public health structures.
AB - Current interest in controlling costs of health care and improving systems of
health services leads state governments to consider reorganizing units of
government responsible for health. Based on a case study of the 1989
establishment of the Washington State Department of Health, concepts from
political science and organizational theory are linked into a process model
useful in planning and supporting reorganization of executive branch agencies.
With the model in mind, public health professionals can work more effectively to
ensure that the paradigm on which a reorganization is based fits desired public
health goals, and can make lobbying more effective.
PMID- 10187065
TI - Transforming public health through distance learning.
AB - Public health agencies face old and new problems in the next century: emerging
infectious and chronic diseases, health problems related to personal behaviors, a
changing demography, and a deteriorating physical and social environment. To meet
these challenges, public health agencies should consider the following: the
advent of new communications technologies, the need for a strong workforce, and
the need for new partnerships. Distance learning can serve as a means to
facilitate a strong workforce and new partnerships.
PMID- 10187066
TI - "A satellite primer on tuberculosis:" a collaboration in distance education.
AB - "A Satellite Primer on Tuberculosis" was offered as a distance-based certificate
course on tuberculosis (TB) fundamentals to a national audience of over 5,000
individuals. The course was a collaborative effort of a school of public health,
a state health department, and the Centers for Disease Control and Prevention.
Instruction was provided through print-based self-study modules that were
complemented by live, interactive satellite conferences. Course completers, over
70 percent of whom were nurses and employees of public health departments, scored
significantly higher on a course posttest than on a pretest, and the vast
majority felt the course provided valuable training.
PMID- 10187067
TI - Causes, costs, and estimates of rabies postexposure prophylaxis treatments in the
United States.
AB - The incidence of rabies in humans in the United States is low. However, contacts
with potentially rabid animals result in thousands of human rabies postexposure
prophylaxis treatments (PEPs) each year. PEP is expensive, not without risk of
adverse reactions, and in many instances unnecessary. Increased reports of cases
of rabies in animals (4,880 cases in 1990, 9,495 in 1993, and 7,124 in 1996)
suggested that PEPs could be increasing. Application of 1981 PEP incidence rates
gave an estimate of approximately 16,000 PEPs during 1996, while calculations
based on annual sales of a rabies biological during 1996 gave an estimate of
approximately 39,000 PEPs. Appropriate usage of PEP requires careful evaluation
of human exposure scenarios and adherence to approved guidelines.
PMID- 10187068
TI - Factors associated with repeat mammography in a New York State public health
screening program.
AB - Screening mammography is the most effective method for early detection of breast
cancer, but repeat mammography rates are not optimal in most populations. Since
1988, New York State has supported a program of breast cancer screening for
underserved, uninsured, or underinsured women. The present study was designed to
identify sociodemographic and clinical factors associated with failure to return
for repeat mammography screening after a negative initial mammogram. Of women
initially screened between 1988 and 1991 (N = 9,485), 27 percent obtained repeat
mammograms by 1993. The final logistic regression model contained program site,
race and ethnicity, family income, and time since last mammogram.
PMID- 10187069
TI - Total quality management in the delivery of public health services: a focus on
North Carolina WIC programs.
AB - Principles of quality improvement have been successfully implemented in the for
profit sector of the United States economy. The purpose of this study is to test
the use of quality improvement strategies including development of leadership
skills, a focus on internal quality, ongoing training and staff development, and
efficient use of resources in the delivery of services in the public sector. The
emphasis of this study is strategies for improving the delivery of nutrition
education and supplemental foods to high-risk women, infants, and children
through a federally funded program called WIC.
PMID- 10187070
TI - Evaluating interventions for prevention and control of infectious diseases, Part
2.
AB - This article, the second of a two-part series, describes approaches to evaluate
interventions for prevention and control of infectious diseases. Evaluation
should take place at all stages in the development and application of such
interventions, whether preventive or therapeutic. At least four different types
of evaluation can be carried out: developmental evaluation, relevance evaluation,
process (administrative) evaluation, and impact evaluation. For therapeutic
interventions, cure is the best indicator of effectiveness. For preventive
interventions, reduction in the occurrence of the condition is the best measure
of effectiveness. However, process and administrative evaluation and economic
evaluation also play important roles.
PMID- 10187071
TI - Reproductive health in managed care: prevention must be a priority.
PMID- 10187072
TI - Lessons learned: the managed care experiences of family planning providers.
AB - This article examines key opportunities and obstacles facing community-based
family planning agencies seeking to be "players" in the provision of
contraceptive and related services in the managed care context. Based on
telephone interviews with people working in or closely with a range of family
planning provider agencies in five states, it identifies a range of innovative
strategies that family planning providers have developed in pursuing arrangements
with managed care organizations. It further identifies five difficult issues that
have arisen repeatedly in the course of negotiating or implementing those
arrangements.
PMID- 10187074
TI - Removing barriers and improving choices: a case study in reproductive health
services and managed care.
AB - Managed care contains inherent structural features that can create obstacles to
time-sensitive, confidential reproductive health services. Such structural
impediments often exacerbate the sociocultural barriers that have historically
affected low-income women--the population that has been targeted for mandatory
enrollment in Medicaid managed care plans in many states. This article recommends
public policy strategies to overcome and prevent multiple barriers that were
identified in a New York-based study in 1995, which focused on access to
reproductive health services in managed care settings. This article also includes
updated evidence supporting the study's findings and its relevance to other
states.
PMID- 10187073
TI - Medicaid and managed care: meeting the reproductive health needs of low-income
women.
AB - State Medicaid programs have increasingly turned to managed care with hopes of
controlling spending while improving access to care. The move to managed care has
significant implications for the provision of reproductive health services-
family planning, abortion, sterilization, sexually transmitted diseases, and
maternity care. However, the delivery of reproductive health services in a
Medicaid managed care environment is wrought with many difficulties. The
complexity inherent in Medicaid policy, the changing world of managed care, and
the health and social needs of the Medicaid population are compounded by the
sensitive nature of reproductive health needs.
PMID- 10187075
TI - Managed care and the prevention of unintended pregnancy.
AB - Managed care organizations (MCOs) hold the potential to help address the
significant public health issue of unintended pregnancy. Managed care's delivery
of women's primary care and family planning services is reviewed. Some MCOs
provide better coverage of contraceptive options as well as better
confidentiality protections, but not enough is being done in partnering with
existing family planning providers and in educating providers about the need to
provide family planning counseling, particularly for adolescents. Performance
indicators should be developed to create incentives for health plans to assess
their success in reducing unintended pregnancy within their enrolled populations.
PMID- 10187076
TI - Freedom of choice: Medicaid, managed care, and California family planning
clinics.
AB - Access to out-of-plan family planning services for Medicaid beneficiaries
enrolled in managed care plans in California has been limited by poor
relationships between family planning clinics and contracting managed care plans.
Plans either delay or fail to reimburse claims from non-network family planning
agencies; family planning staff are unmotivated to identify managed care members
through financial screening, to cover costs with other funds, or to refer members
back to plan. In addition, plans and clinics fail to coordinate the care of
managed care clients by sharing medical records. Based on findings from a pilot
project, California will try to facilitate relationships between plans and family
planning agencies rather than directly pay out-of-plan claims.
PMID- 10187077
TI - The transition to managed care: experiences of planned parenthood patients.
AB - A review of the findings from a 1996 survey of women visiting a Planned
Parenthood clinic reveals that some members of managed care organizations (MCOs)
may not be receiving appropriate preventive services and information from their
primary care providers. This article details the results of a survey of 115 women
who attended a Planned Parenthood of New York City clinic for reproductive health
services. Based on these survey findings, the authors provide recommendations for
MCOs and traditional providers of reproductive health to improve service
delivery.
PMID- 10187078
TI - Formative research for interventions among adolescents at high risk for gonorrhea
and other STDs.
AB - The gonorrhea infection rate among 15-19 year olds during 1993-1994 in an urban
Upstate New York community was nearly twice the national norm. More than 50% of
all the gonorrhea cases were concentrated in eight census tracts. This study was
conducted to provide data regarding sexually transmitted diseases among high risk
adolescents to increase successful public health interventions. The methodology
consisted of six focus groups and a self-administered survey. The results
determined the extent of accurate knowledge, their risk behaviors and beliefs,
the barriers to treatment, and suggested interventions for clinic services and
health education.
PMID- 10187079
TI - Assessing the impact of Medicaid managed care on TB activities in local health
departments.
AB - Three in-depth case studies were conducted to explore the impact of Medicaid
managed care on local health department prevention activities. Tuberculosis (TB)
was selected as a sentinel issue because TB includes both clinical treatment and
population-based public health considerations (such as surveillance and contact
tracing). Overall, study results indicated that there has been a minimal impact
on TB prevention and control services, primarily because few TB patients are
served by managed care. However, the sites offer many suggestions for areas to
monitor, possible collaborative opportunities, and mechanisms to assure continued
TB prevention and control.
PMID- 10187080
TI - Impact of Medicaid resources on core public health responsibilities of local
health departments in Illinois.
AB - With Illinois' plan to embark on a statewide Medicaid managed care program, the
impact of Medicaid resources on core public health responsibilities of local
health departments (LHDs) was assessed and found to be substantial. A reduction
of $330,000 in core public health activities would likely accompany each $1
million in Medicaid resources lost by these LHDs. Only by actively participating
in the planning and implementation of these conversions can public health
agencies maintain high productivity and efficiency in addressing core public
health responsibilities in their communities.
PMID- 10187081
TI - Immunization coalitions that work: training for public health professionals.
AB - Coalition development is a major strategy to increase immunization rates.
However, if local and state coalitions are to succeed, their staffs need training
and technical assistance in coalition development, community planning, and
program implementation. The National Coalition Training Institute trains key
health agency staff in 87 state, territorial, and urban sites to perform needs
assessments, use data to guide planning, plan comprehensive strategies, and
evaluate their coalitions. The curriculum is based on training needs that are
identified by a national survey of immunization coalitions, effective approaches,
and participant evaluation. According to evaluations conducted during its first
year, the National Coalition Training Institute is meeting the needs of
participants.
PMID- 10187082
TI - The use of prevalence data to unite the community in prevention programs.
AB - This study examined the prevalence of cigarette smoking in a three-county area of
northeastern Pennsylvania. More than 14,000 questionnaires have been returned,
and results reveal that 5,411 children have experimented with cigarettes and
2,962 of those children continue smoking today. Cigarette experimentation begins
as early as age 5 in northeastern Pennsylvania, with the highest number of
children (19.8%) experimenting by age 12. This experimentation occurs less
frequently among females in the lower grades and more frequently among females in
the later years of high school. The results of this study were used to unite the
health community of northeastern Pennsylvania in a number of prevention
initiatives.
PMID- 10187083
TI - An evaluation of professional education efforts for breast and cervical cancer in
public health nurses.
AB - This article describes training programs instituted in 1992 by the North Carolina
Breast and Cervical Cancer Control Program (BCCCP) to improve skills of public
health nurses in breast and cervical cancer education and clinical services.
Public health nurses traditionally serve as primary health care providers in
medically underserved communities and are the main providers of BCCCP services.
The training programs were evaluated by a statewide survey of public health
nurses in 1996. The authors discuss the findings of this survey, its limitations,
and the goals it has led the authors to set for improving the education program
in the future.
PMID- 10187084
TI - Risky business, Part 2. Violence in the health care environment.
PMID- 10187085
TI - Providing and maintaining a safe workplace.
PMID- 10187086
TI - Healthcare communications--the requirement for flexibility.
AB - This paper has attempted to show how the requirements of bedhead services have
developed and become much more flexible to match the clients' needs. The
outstanding two features that remain most important to the end users are
reliability and flexibility. Whatever systems are installed, the end user must be
satisfied that the equipment will last 15 years and that the supplier will be
around to maintain it, and to add extra features or modify the bedhead services
arrangement in line with changing demands and requirements for hospitals.
PMID- 10187087
TI - The surgery for Dr Pugh & Partners.
PMID- 10187088
TI - Development of voice telecommunication services in the NHS.
AB - There is now an opportunity to accelerate the process of modernisation in the
delivery of healthcare by the use of new technology. Advanced voice services such
as the virtual private network, Centrex and mobile extension facilities are
increasingly used in the NHS to the benefit of staff and patient. The provision
of reliable and feature-rich integrated voice solutions across all groups in the
healthcare arena is an essential factor in the development of new and better
services to the public into the next millennium.
PMID- 10187089
TI - Managing the millennium--pain or progress.
PMID- 10187090
TI - Food safety: a recipe for risk management.
PMID- 10187091
TI - Voices from the front-line. 14-hospital study concludes the results of
reengineering have been "very, very mixed".
PMID- 10187092
TI - Physician incentives. How one IPA gives its physicians feedback on performance
measures.
PMID- 10187093
TI - Ask a cyberdoc. Need a fast answer to a medical question? AOL now lets you talk
to physicans for free.
PMID- 10187094
TI - The biological mother lode.
PMID- 10187095
TI - The DNA detectives.
PMID- 10187096
TI - Getting smart about DNA.
PMID- 10187097
TI - From human embryos, hope for 'spare parts'--but research renews debate over use
of fetal cells.
PMID- 10187098
TI - Surviving the Medicare mess. How to avoid pain when your Medicare HMO shuts down.
PMID- 10187099
TI - Preparing for year 2000--STAT!
AB - Apocalypse or inconvenience? Will you be ready when the clock strikes for the
first time in the Year 2000? Surviving the flip of calendar with systems intact
is the dream of many CIOs. One hospital shares its plan.
PMID- 10187100
TI - Six opinions on IT security. Panel discussion.
AB - Physicians consult over the Internet. Diagnoses are delivered via E-mail. Data is
kept in multimedia repositories. Health care IT is filled with data security
challenges. Here's what six experts think about the possibilities and
vulnerabilities.
PMID- 10187101
TI - Beyond RxD2: linking pharmacists doctors and nurses.
PMID- 10187102
TI - Technology and the business office.
AB - Providing access to information is the key to streamlining business office
operations. Because they broaden access, document imaging, data marts, EDI and
Web-enabled applications are winning a back-office following.
PMID- 10187103
TI - How SelectCare selected a system.
AB - Selecting a managed care system in the absence of a clearly defined business
strategy is like driving across the country without a road map. But SelectCare
didn't let that stop them. Here's their seven-step methodology.
PMID- 10187104
TI - What works. Workflow app trims $150K FTE cost, aids expansion.
PMID- 10187105
TI - What works. Disease management on intranet saves $1.2 million.
PMID- 10187106
TI - What works. PACS eliminates lost film; 18-month ROI on $3 million.
PMID- 10187107
TI - What works. Patient sat tool boosts response rate 70 percent.
PMID- 10187108
TI - HotList: outcomes and quality measurement systems.
PMID- 10187109
TI - The role of the 802.11 Wireless LAN Standard.
PMID- 10187110
TI - Home-based primary care in the VA setting, with a focus on Birmingham, Alabama.
AB - The Veterans Administration Hospital-Based Home Care Program provides
comprehensive primary care to homebound veterans. Unlike Medicare-funded home
care, it is not oriented to episodic provision of skilled nursing care, but
rather to long-term primary care in the home. The interdisciplinary composition
of HBPC teams allows for innovative approaches to care and coordinated
implementation of treatment plans. Outcomes assessment of care provided through
HBPC has been positive, suggesting an overall improvement in function and
decrease in health care costs among those using the HBPC Program. The HBPC
Program offers a tested model of primary home care within a "managed care" model.
Its positive features should be considered by those initiating managed primary
home care within the private sector.
PMID- 10187111
TI - Death in the home: the doctor's responsibility.
AB - The role physicians assume when patients die at home is nebulous and ill defined.
Beyond the traditional function of providing comfort and condolence to family
members, the physician's duties are directed toward how our society deals with
the bureaucratic and legal aspects of death. Statistics are maintained regarding
the numbers of deaths in municipalities and states and the causes of death, and
those numbers are used by individuals and organizations for a multitude of legal,
medical, and political purposes. The state also has an obvious interest in
uncovering and prosecuting crime. The physician has a vital part to play in
providing essential medical information for those record-keeping, statistical,
and legal purposes. Physicians need to be mindful of the important functions
being served when they are asked to complete death certificates and to report
cases and provide information to the medical examiner. As with many other
physician activities, the information we provide about our patients' deaths
serves a singular societal need; thus, we should view that function not as a
burden but as a vital aspect of the enriching and enobling work that is uniquely
ours.
PMID- 10187112
TI - Palliative care: overview of the major hospice movement--some issues and some
answers.
PMID- 10187113
TI - A word from the wizened.
PMID- 10187114
TI - Home health care: supporting vitality for rural elders.
PMID- 10187115
TI - Medicare program; revisions to payment policies under the physician fee schedule
for calendar year 1999--HCFA. Proposed rule.
AB - This proposed rule would make several policy changes affecting Medicare Part B
payment. The changes that relate to physician services include: resource-based
practice expense relative value units, medical direction rules for anesthesia
services, and payment for abnormal Pap smears. Also, we would rebase the Medicare
Economic Index from a 1989 base year to a 1996 base year. Under the law, we are
required to develop a resource-based system for determining practice expense
relative value units. The Balanced Budget Act of 1997 (BBA 1997) delayed, for 1
year, implementation of the resource-based practice expense relative value units
until January 1, 1999. Also, BBA 1997 revised our payment policy for nonphysician
practitioners, for outpatient rehabilitation services, and for drugs and
biologicals not paid on a cost or prospective payment basis. In addition, BBA
1997 permits certain physicians and practitioners to opt out of Medicare and
furnish covered services to Medicare beneficiaries through private contracts. In
addition, since we established the physician fee schedule on January 1, 1992, our
experience indicates that some of our Part B payment policies need to be
reconsidered. This proposed rule is intended to correct inequities in physician
payment and solicits public comments on specific proposed policy changes.
PMID- 10187116
TI - Quality mammography standards; correcting amendment--FDA. Final rule; correcting
amendment.
AB - The Food and Drug Administration (FDA) is correcting its regulations governing
mammography, published in a document entitled "Quality Mammography Standards"
that appeared in the Federal Register of October 28, 1997. The regulations are
effective April 28, 1999; except section 900.12(b)(8)(i), (e)(4)(iii)(B), and
(e)(5)(i)(B), which become effective October 28, 2002. The October 28, 1997,
document was published with some inadvertent typographical errors. Some of those
errors were corrected in a document entitled "Quality Mammography Standards;
Correction" that appeared in the Federal Register of November 10, 1997, but
additional typographical errors occurred in the publication of this document. In
addition, since November 10, 1997, certain other problems with the text of the
regulations have been identified that, if uncorrected, would lead to unforeseen
and undesirable consequences. This document corrects those errors.
PMID- 10187117
TI - Notice regarding HRSA grant requirement--participation in the 340B drug pricing
program--HRSA. Notice.
AB - Section 602 of Public Law 102-585, the "Veterans Health Care Act of 1992,"
enacted section 340B of the Public Health Service (PHS) Act, "Limitation on
Prices of Drugs Purchased by Covered Entities." Section 340B provides that a
manufacturer who sells covered outpatient drugs to eligible entities must sign a
pharmaceutical pricing agreement with the Secretary of HHS in which the
manufacturer agrees to charge a price for covered outpatient drugs that will not
exceed that amount determined under a statutory formula. The purpose of this
notice is to request comments on a proposed grant award requirement in which all
entities, except those entities which fall within excepted categories, that
receive HRSA grants listed in section 340B(a)(4) and that purchase or reimburse
for covered outpatient drugs must participate in the 340B Drug Pricing Program,
or demonstrate good cause for nonparticipation. When the Prime Vendor program is
operational, HRSA intends to publish a second Federal Register notice proposing
an expansion of the grant award requirement to include participation in the Prime
Vendor Program.
PMID- 10187118
TI - Summary of precedent opinions of the General Counsel--VA. Notice.
AB - The Department of Veterans Affairs (VA) is publishing a summary of legal
interpretations issued by the Department's General Counsel involving veterans'
benefits under laws administered by VA. These interpretations are considered
precedential by VA and will be followed by VA officials and employees in future
claim matters. The summary is published to provide the public, and, in
particular, veterans' benefit claimants and their representatives, with notice of
VA's interpretation regarding the legal matter at issue.
PMID- 10187119
TI - Federal employees health benefits program: disenrollment--OPM. Final rule.
AB - The Office of Personnel Management (OPM) is issuing final regulations that are
consistent with existing administrative procedures requiring employing offices to
provide information about enrollees in the Federal Employees Health Benefits
(FEHB) Program to the carriers of the FEHB plans in which they are enrolled.
Carriers are also required to use the information provided by employing offices
to reconcile their enrollment records. These regulations will regularize the
conditions that would allow carriers to disenroll individuals when their
employing office of record does not show them as enrolled in the carrier's plan
and the carrier is otherwise unable to verify the enrollment. The purpose of
these regulations is to facilitate reconciliation of carrier and employing office
enrollment records, especially in cases where the carrier has not previously
received a notice showing an enrollment no longer is valid.
PMID- 10187120
TI - Tamper-evident packaging requirements for over-the-counter human drug products-
FDA. Final rule.
AB - The Food and Drug Administration (FDA) is amending its regulations on tamper
resistant packaging to require that all over-the-counter (OTC) human drug
products marketed in two-piece, hard gelatin capsules be sealed using a tamper
evident technology; to change the term "tamper-resistant" in the labeling of all
OTC drug products to "tamper-evident;" and to specify that the required OTC drug
product labeling statement must refer to all packaging features used to comply
with the tamper-evident packaging requirements, including those on the secondary
package, the immediate container or closure, and any capsule sealing technologies
used. FDA is taking this action as a result of its continuing review of the
potential public health threat posed by product tampering and to improve consumer
protection by addressing specific vulnerabilities in the OTC drug market.
PMID- 10187121
TI - Recognition of organizations and accreditation of representatives, attorneys, and
agents--VA. Proposed rule.
AB - The Department of Veterans Affairs (VA) proposes to revise existing procedures
and requirements regarding recognition of service organizations and accreditation
of their representatives and agents, attorneys, and individuals seeking to
represent claimants for benefits administered by VA. These amendments are
necessary to improve clarity and to enhance VA's ability to assure high quality
representation of claimants.
PMID- 10187122
TI - Workers of the world, insure!
PMID- 10187123
TI - Autopsy reveals patient rights legislation may have been dead for several months.
PMID- 10187124
TI - Compensation monitor. Which grows faster: grass or compensation?
PMID- 10187125
TI - PSOs: what happened?
PMID- 10187126
TI - Information underload: why claims data fall short.
PMID- 10187127
TI - HEDIS: looking at the numbers. Clinically, for-profits lag not-for-profits.
PMID- 10187128
TI - The promise and problems of limited access. A conversation with Michael J.
Dillon, R.Ph.. Interview by Patrick Mullen.
PMID- 10187129
TI - Ethics of alternative medicine: the unconventional has its place.
PMID- 10187130
TI - HCFA needs to shine some light through Stark II's murkiness on 'gifts'.
PMID- 10187131
TI - Managed care outlook. 'I want what I want, or I'm outta here'.
PMID- 10187132
TI - Using the old with the new.
AB - Not long ago, traditional health care practitioners viewed complementary medicine
as ineffective and scientifically suspect. But recent studies on the efficacy of
complementary procedures are convincing more doctors to try these techniques as a
way to complement the more traditional treatments they prescribe.
PMID- 10187133
TI - Reach out and read.
PMID- 10187134
TI - "Lie-ability" in hiring.
AB - Recent political events in the news and the seemingly endless, evasive
wordsmithing in our legal system suggest that the ancient practice of lying has
been elevated to an art form. Telling the truth has often been reduced to
semantical compliance with factual definitions.
PMID- 10187135
TI - A product consumers want.
AB - From medical evidence of efficacy and positive health outcomes, to economic
assessments suggesting cost savings opportunities, alternative health care has
become an influential product type. From a marketing standpoint, alternative care
has provided the health care industry with an opportunity to introduce a product
that consumers really want. Health care organizations everywhere are encouraged
to meet the demand now and begin examining how they can integrate alternative
care into more traditional medical programs.
PMID- 10187137
TI - Community benefit planning. The missing link in community health models.
PMID- 10187136
TI - Are "off-labels" legal?
AB - A doctor prescribes a beta-blocker to calm a patient's muscle tremors, even
though the Food and Drug Administration (FDA) has only approved the drug for use
in lowering blood pressure. A physician recommends that a patient wear a nicotine
patch as a treatment for colitis. A pediatrician prescribes a drug that has been
approved for adult use only. Such "off-label" prescriptions are increasingly
common--and legal.
PMID- 10187138
TI - Measuring quality of care.
PMID- 10187139
TI - Taking an alternative risk.
AB - Pharmacists and other health care providers that recommend "alternative
medicines" could be exposed to malpractice as well as product liability claims in
the event a patient is either injured by or has treatment inappropriately delayed
based on their recommendation of such medicine. For purposes of this article, it
is assumed that alternative medicines are nonprescription (over-the-counter
[OTC]) food supplements, vitamins, herbs or other substances contained in
commercially available products. Many of these products are sold in pharmacies or
health food stores and have not been clinically tested or do not have a
scientific basis for the use for which they are recommended.
PMID- 10187140
TI - The quest for clarity. The ins and outs of an excess benefit transaction.
AB - On July 30, 1998, the IRS issued proposed regulations to implement the
intermediate tax sanctions of the Tax Payers Bill of Rights II Act of 1996. The
intermediate sanctions, now codified at Section 4958 of the Internal Revenue
Code, provide for the imposition of penalty taxes where a tax-exempt entity
participates in an "excess benefit transaction."
PMID- 10187141
TI - Prepaid convenience.
AB - Consider prepaid calling cards as a new tool in your marketing arsenal. Your
hospitality facility may be considering the sale and distribution of prepaid
phone cards to provide more convenience to patients or as a replacement to
traditional calling cards for mobile employees. Prepaid phone cards represent a
new twist and many advantages for long distance calling.
PMID- 10187142
TI - A caring presence.
PMID- 10187143
TI - How to keep your customers.
PMID- 10187144
TI - Exploring integrative medicine.
PMID- 10187145
TI - How to show care for seniors.
PMID- 10187146
TI - The "health" in healthy communities.
PMID- 10187147
TI - Looking at the alternatives.
AB - "Are there alternatives to this treatment?" In the recent past, many health care
providers have been unable to fully answer that question. But as health care
continues to evolve, increasing numbers of physicians, hospitals and medical
schools are determining that complementary and alternative medicine does have a
place in quality patient care.
PMID- 10187148
TI - Physician profiling: it's here, get used to it.
PMID- 10187149
TI - Proving "physician need" is the key to compliance.
PMID- 10187150
TI - When the technical is crucial: looking at IBNR (incurred but not reported).
PMID- 10187151
TI - HCFA corrects PPS interim final rule, clarifies assessment dates.
PMID- 10187152
TI - Most FIs ready to process PPS claims; retroactive adjustments may take longer.
PMID- 10187153
TI - How to avoid the compliance pitfalls of PPS.
PMID- 10187154
TI - HCFA still working on calculation of Part B add-ons for some providers.
PMID- 10187155
TI - HCFA releases 1999 physician fee schedule; will be used in payment of outpatient
rehabilitation.
PMID- 10187156
TI - Reengineering routine services under PPS.
PMID- 10187157
TI - AHCA urges expanded definition of "new" provider under SNF PPS.
PMID- 10187158
TI - Shrubbery, sheets, shovels & sheen.
PMID- 10187159
TI - Preventing malnutrition in nursing facilities--the responsibility of every health
care provider. Nutrition Screening Initiative.
PMID- 10187160
TI - Hire an effective MDS coordinator.
PMID- 10187161
TI - Quality in an era of cost containment.
PMID- 10187162
TI - A busy person's challenge. How to say no.
PMID- 10187163
TI - Synergy: Internet + e-mail = success. It's not either or, but both!
PMID- 10187164
TI - Federal report calls for national criminal background checks.
AB - If the Kohl bill is not passed in the 105th Congress, look for the legislative
proposal to be reintroduced next year, Lynn Becker, a spokesperson for Sen. Kohl
tells Balance. "Hopefully," she adds, "the administration will include the
National Background Check Registry as part of its next Budget Proposal, which is
expected to be submitted to Congress in February 1999."
PMID- 10187165
TI - Checking applicant backgrounds.
PMID- 10187166
TI - Medicare providers, plans may suffer regulation overkill.
PMID- 10187167
TI - Despite Medicare+Choice changes, rural providers cautious about risk.
AB - Rural providers discover why it's a tough go in the heartland for Medicare risk.
Despite changes in the Medicare risk program designed to encourage managed care
for seniors in rural areas, big HMOs are withdrawing from these small markets in
droves. Provider groups in Nebraska working on developing their own Medicare risk
plan explain the challenges.
PMID- 10187168
TI - Partner with state to shape programs that manage Medicaid special needs patients.
AB - Hold on to your Medicaid special needs population by partnering with your state.
Rather than waiting for managed care to engulf its patient base, the Shepherd
Center in Atlanta proactively is working on a pilot program with the state to
manage patients physical disabilities in hopes it will be a model for the
Medicaid special needs population.
PMID- 10187169
TI - Medicare market analysis targets the services seniors want most.
AB - Data File: A Medicare market analysis by the Evanston, IL-based Sachs Group shows
how knowing your market can help direct you to the services your seniors want and
need, to keep them in plans. Learn how such analyses can help you determine what
benefits you and your plan should offer enrollees.
PMID- 10187170
TI - Use financial analysts' methods to assess the strength to Medicare risk plans.
AB - Does your Medicare HMO have the financial strength to keep its promises? Weiss
Ratings Inc. in Palm Beach Gardens, FL, shares some of the financial indicators
used by analysts, raters, and state insurance regulators to assess HMO plans--and
outlines five tips that will help you judge just how financially sound your
Medicare risk plan really is.
PMID- 10187171
TI - Strive to limit risk exposure on seniors with Alzheimer's.
PMID- 10187172
TI - The white coat syndrome.
PMID- 10187173
TI - A review of breast conservation in Columbia/HCA healthcare facilities.
PMID- 10187174
TI - Intangibles in mergers and acquisitions--a critical success factor in modern day
health care.
PMID- 10187175
TI - Process enhancement by using MultiLeaf Collimator (MLC) technology.
PMID- 10187176
TI - Marketplace. Recent losses in liability lawsuits portend problems for HMOs.
PMID- 10187177
TI - Perspectives. Facing SCHIP's (State Children's Health Insurance Program) acid
test: getting kids care once they're covered.
PMID- 10187178
TI - Marketplace. AMA sets campaign to punish doctors who base testimony on 'junk
science'.
PMID- 10187179
TI - Perspectives. Managed care forces new attempts to answer old questions about
relationship between public health and medical care.
PMID- 10187180
TI - Perspectives. Getting into compliance--avoiding the treacherous terrain of fraud
and abuse.
PMID- 10187181
TI - Marketplace. New Jersey says its report card shows all HMOs must improve
preventive care.
PMID- 10187182
TI - Perspectives. 'Privatization' sweeps through public behavioral care programs, but
community providers maintain key role on front lines.
PMID- 10187183
TI - Technology, old-fashioned touch create new model of health care.
PMID- 10187184
TI - Study pinpoints savings areas for redesign.
PMID- 10187185
TI - Access 2000: a road more traveled.
PMID- 10187186
TI - Patient education is large piece of DM puzzle.
PMID- 10187187
TI - Patients visit community without leaving hospital.
PMID- 10187188
TI - Use creativity to design real-life experiences.
PMID- 10187189
TI - Lethal drug abuse act fails this session.
PMID- 10187190
TI - Public, private hospitals square off over Medicare DSH (disproportionate share
hospital).
PMID- 10187191
TI - A conversation with ... C. Duane Dauner.
PMID- 10187192
TI - Washington's mystery of margins.
PMID- 10187193
TI - Providers facing prompt payment issues in Medicare, managed care.
PMID- 10187194
TI - Improving healthcare delivery in rural markets: the HMA (Health Management
Associates) experience.
PMID- 10187195
TI - Hypothecated taxes and NHS funding.
PMID- 10187196
TI - Context, convergence and contingency.
PMID- 10187197
TI - The limits of leadership: opinion leaders in general practice.
AB - OBJECTIVE: To explore the importance and characteristics of opinion leaders in
general practice, particularly in relationship to the use of laboratory tests.
DESIGN: Focus group discussions and a mailed survey. SUBJECTS: Five focus groups
(n = 29 participants) in four different municipalities and a random sample of 85
general practitioners (GPs) in Norway. RESULTS: While Norwegian GPs recognised
colleagues who were influential in determining how they practised, they found it
difficult to identify opinion leaders specifically with respect to the use of
laboratory tests. Opinion leaders were thought to be less important in
influencing the use of laboratory tests than continuing medical education
activities and practice guidelines, but more important than industry, patients or
personal financial interests. Norwegian GPs recognised and characterised opinion
leaders in much the same way as physicians in the USA. Influential colleagues
were characterised as being good conveyers of information and willing to take
time, as well as being up-to-date and having a high level of clinical expertise.
GPs expressed a negative attitude towards 'superspecialists' who give advice
without knowing the epidemiology of general practice, people who are arrogant and
people who do not show respect towards GPs. CONCLUSIONS: The potential to
identify and use opinion leaders to improve the use of laboratory tests by GPs in
Norway appears to be limited.
PMID- 10187198
TI - Can we trust the quality of routine hospital outpatient information in the UK?
Validating outpatient data from the patient administration system (PAS).
AB - BACKGROUND: A validation study of routine hospital outpatient data was carried
out as part of a broader project focusing on outpatient re-attendance. The aim
was to compare two patient administration system (PAS) data items with the same
information collected directly from hospital clinicians. METHODS: A total of 140
cases from four specialties at four National Health Service hospitals was
randomly selected for comparison. The specific data items compared were the grade
of doctor seen and the management decision taken following an outpatient
appointment. The proportion of cases in which there was agreement was calculated,
together with kappa values and relevant statistics indicating the accuracy of the
PAS data when compared with information compiled immediately after the
consultation by the relevant clinician. RESULTS: There was agreement between the
clinician's data and the PAS data in 118/140 (84.3%) cases for grade of doctor
seen and in 105/139 (76.7%) cases for the management decision. There was complete
agreement for both items in 88/139 (62.6%) cases. Kappa values indicated good
agreement between the two data sources. However, 'sensitivity' statistics
suggested that the likely accuracy of each data item varied. CONCLUSION: Although
there was good agreement within individual categories between the two sources,
37% of patient computerised records held at least one inconsistency in this small
study focusing on only two data items. Further systematic evaluation is needed to
test the extent to which other items are similarly discrepant.
PMID- 10187199
TI - Do minutes count? Consultation lengths in general practice.
AB - OBJECTIVE: To document the variability in consultation length and to examine the
relative weight of different kinds of characteristics (of the patients, of the
general practitioner (GP), or of the practice) in affecting consultation length,
and, thus, to assess whether consultation length can legitimately be used as a
quality marker. DESIGN: A multilevel statistical analysis of 836 consultations
across 51 GPs in ten practices. SETTING AND SUBJECTS: Ten general practices
across four regions in England with varying list sizes, number of partners and
fundholding status. MAIN OUTCOME MEASURES: Length of time face-to-face with
patients in consultation measured in minutes and fractions of minutes. RESULTS:
There is substantial inter-practice variation in consultation length, from a mean
of 5.7 minutes to one of 8.5 minutes. In some practices the longest average GP
consultation time is about twice that of the shortest. Trainees and new partners
spend, on average, about 1 minute less than their longer-serving colleagues.
Consultation lengths for individual GPs range from a mean of 4.4 minutes to 11
minutes. Late middle-aged women (55-64 years) receive the longest consultations,
followed by elderly people, with children receiving the shortest consultations.
The number of topics raised affects the length of the consultation by about 1
minute per additional topic. When female patients consult female GPs,
approximately 1 minute is added to the average consultation. A significant
fraction of the variability in consultation lengths can be explained in terms of
characteristics of patients, of GPs and of practices. CONCLUSIONS: The fact that
there is little unexplained variation in GP consultation lengths that might be
attributable to variations in quality (i.e. GP-related) throws doubt on the
proposition that length of consultation can be used as a marker for quality of
consultation in general practice.
PMID- 10187200
TI - Comment: do minutes count for quality in the general practice consultation?
PMID- 10187201
TI - Does new technology increase or decrease health care costs? The treatment of
peptic ulceration.
AB - OBJECTIVES: To determine whether new technology increases or decreases formal
health care costs, with reference to the diagnosis and treatment of peptic
ulcers. METHODS: A costing method has been devised which is designed to
investigate directly the way in which the costs to formal health services of
diagnosing and treating an individual illness have changed with changes in
technology. RESULTS: The cost of diagnosis has increased almost entirely as a
result of the high cost of endoscopy compared with X-ray examination. The
introduction of H2-receptor antagonist drugs increased the cost of treatment
compared with the earlier phases of surgical treatment. Subsequently,
Helicobacter pylori eradication treatment has reduced the cost of treatment
compared with all earlier phases of technology. CONCLUSIONS: A method has been
devised that allows the impact of changes in medical technology on formal health
care costs to be investigated for individual illnesses. In the treatment of
peptic ulceration, the current technology, H. pylori eradication, has lower
treatment costs than all previous technologies. The evidence from previous
studies and this study is insufficient to support the assertion that new
technology in general leads either to an increase or to a decrease in health care
costs.
PMID- 10187203
TI - Simulation applied to health services: opportunities for applying the system
dynamics approach.
AB - The aim of this essay is to raise awareness and broaden understanding within the
health services community of the system dynamics (SD) simulation approach to
policy analysis. The application of simulation in health services is reviewed. A
comparison is made between the SD and traditional simulation approaches and is
illustrated by considering reductions in waiting times for coronary heart disease
treatment. Traditionally, simulation studies have tended to focus on the analysis
of localized decisions and therefore on problems orientated towards individual
patients. Although these methods are extremely powerful and effective, there is
scope for an alternative modelling approach which is based on a more holistic
perspective; SD is one such approach. It can assist in the design of robust
policies by supporting debate on how the underlying structure might influence the
evolutionary behaviour of a system. Using this method we can consider the time
variation both of tangibles, such as waiting times and health care costs, and
intangibles, such as patient anxiety and the effects of various pressures on
purchasing decisions. We propose that SD holds great potential in assisting
policy formation in health care.
PMID- 10187202
TI - Advice provided in British community pharmacies: what people want and what they
get.
AB - OBJECTIVES: This study explored advice-giving behaviour in community pharmacies
in order to understand the nature and process of pharmaceutical consultations and
consumers' views of the advice-giving role. METHOD: An ethnographic research
strategy was used, combining patient interviews with non-participant observation
of interactions between consumers and pharmacy staff. One week was spent in each
of 10 pharmacies. RESULTS: The study demonstrated that the advice given in a
community pharmacy is almost wholly focused on product recommendation and use.
Advice-giving varies according to whether consultations concern prescription or
non-prescription medicines. When the latter are involved, advice-giving is mostly
consumer-led. Consumers' major 'need' for pharmacy services appears to be for
information about the effectiveness of products they buy, whilst pharmacists and
pharmacy assistants concentrate on providing advice on the safety of medicines.
CONCLUSION: The notion of pharmacists as general health advisors does not appear
to be shared by the public and may be at odds with how the public view and use
pharmacies. Protocols to guide staff may be improved by including the consumer
perspective. Most consumers have previous experience of their ailments and use
pharmacies as one of several resources available to them to treat their minor
illness, having made their own diagnosis and assessment before entering the
pharmacy. The scope for giving new advice is therefore limited. The broader role
of community pharmacies merits further attention.
PMID- 10187204
TI - The distribution of health care costs and their statistical analysis for economic
evaluation.
AB - OBJECTIVE: Where patient level data are available on health care costs, it is
natural to use statistical analysis to describe the differences in cost between
alternative treatments. Health care costs are, however, commonly considered to be
skewed, which could present problems for standard statistical tests. This review
examines how authors report the distributional form of health care cost data and
how they have analysed their results. METHOD: A review of cost-effectiveness
studies that collected patient-level data on health care costs. To supplement the
review, five datasets on health care costs are examined. Consideration is given
to the use of parametric methods on the transformed scale and to non-parametric
methods of analysing skewed cost data. RESULTS: Since economic analysis requires
estimation in monetary units, the usefulness of transformation-based methods is
limited by the inability to retransform cost differences to the original scale.
Non-parametric rank sum methods were also found to be of limited use for economic
analysis, partly due to the focus on hypothesis testing rather than estimation.
Overall, the non-parametric approach of bootstrapping was found to offer a useful
test of the appropriateness of parametric assumptions and an alternative method
of estimation where those assumptions were found not to hold. CONCLUSIONS:
Guidelines for the analysis of skewed health care cost data are offered.
PMID- 10187205
TI - Advances in hospital outcomes research.
PMID- 10187206
TI - Evidence-based policy: rhetoric and reality.
AB - Evidence-based policy has been hailed as the current zeitgeist in health care.
Its intuitive appeal is clear but its implementation is problematic. This case
study demonstrates the practical difficulties of using this approach for
purchasing health care. New technologies suffer from limited knowledge about both
their long-term benefits and their adverse effects. This undermines attempts to
assess effectiveness and efficiency in local populations. Furthermore, the use of
evidence should not be assumed to eliminate the need to apply value judgements,
which has repercussions for the attainment of equity of access to health care. It
is therefore unrealistic to view this approach as a panacea. Rather, evidence
based medicine should contribute to the decision-making process, in conjunction
with other considerations such as equity and patient preference.
PMID- 10187207
TI - Ambulatory DVT (deep vein thromboembolism) management is a good deal for the
right patients.
PMID- 10187208
TI - Real world data on outpatient VTE (venous thromboembolism) therapy are hard to
ignore.
PMID- 10187209
TI - Health plans, providers embracing alternative medicine.
PMID- 10187210
TI - Concentrating on top 10% contributes most to bottom line.
PMID- 10187211
TI - Providers wagering more than they measure in risk contracts.
PMID- 10187212
TI - Atlanta clinics struggle through wariness en route to successful merger.
PMID- 10187213
TI - Year 2000 clock ticking, requires senior management attention.
PMID- 10187214
TI - Price vs. quality--the elusive struggle.
PMID- 10187215
TI - Amid complex Medicaid regulations, plans find customers' 'hot buttons'.
PMID- 10187216
TI - Medicare profitability demands effective investments, relations.
PMID- 10187217
TI - Rising demand for specialists forces a new look at options.
PMID- 10187218
TI - EDI is key to operational savings but demands new attitude.
PMID- 10187219
TI - Creative collaborations deliver healthcare to Medicaid patients.
PMID- 10187220
TI - The effect of grading and publicizing the physician groups' performance.
PMID- 10187221
TI - Downsizing mental health networks may not be cost effective.
PMID- 10187222
TI - Banks, health plans can work together to capture small business market.
PMID- 10187223
TI - Successful implementation of a comprehensive computer-based patient record system
in Kaiser Permanente Northwest: strategy and experience.
AB - Kaiser Permanente Northwest (KPNW) has implemented a computer-based patient
record (CPR) system for outpatients. Clinicians at KPNW use this comprehensive
CPR to electronically document patient encounters; code diagnoses and procedures;
maintain problem lists; order laboratory tests, radiology tests, and
prescriptions; and send patient-specific messages and referrals to other medical
providers. More than 700 clinicians, representing more than 20 medical and
surgical specialties, and 2600 support staff in 31 geographically separate sites
use this system as the information foundation of delivery and documentation of
health care for KPNW's membership of 430,000. As of May 1998, more than four
million visits and two million telephone calls had been processed and documented
into the system. More than 5000 outpatient visits are processed and documented
each weekday. From an integrated clinical workstation, clinicians also access e
mail, an extensive results-reporting system, and sites on both the internet and
KPNW's intranet. This article describes a strategy for and experience with the
implementation of a large-scale, comprehensive CPR in an integrated HMO. This
information may be useful for persons attempting to implement CPRs in their own
institutions.
PMID- 10187224
TI - Population health management with computerized patient records.
AB - CIGNA Healthcare of Arizona is using a computerized patient record system
(EpicCare) for all medical care delivery at two primary care clinics. Use of this
technology to improve quality of care for healthy populations and targeted groups
of at-risk persons has led to population health management. This paper discusses
strategies used in these endeavors.
PMID- 10187226
TI - Support of quality and business goals by an ambulatory automated medical record
system in Kaiser Permanente of Ohio.
AB - Kaiser Permanente of Ohio has developed a Medical Automated Record System (MARS)
to address the business and clinical needs of the organization. The system is
currently used by 220 physicians and 110 allied health personnel. To support the
quality initiatives of the organization, the system has been programmed to
generate reminders, at the moment of care, on compliance with clinical
guidelines. This article details examples of compliance improvements with
guidelines for the use of aspirin in coronary artery disease, use of influenza
vaccinations in members older than 64 years of age, and stratification of
asthmatic patients into severity levels; it also summarizes other quality
improvements. MARS provides a data stream for electronic billing, which saves the
organization the cost of manual billing. In addition, this system reduces
operating costs, in particular the number of staff needed to deliver charts and
the cost of printing forms. Cost-benefit analysis demonstrates that the system
can produce savings in excess of maintenance costs.
PMID- 10187225
TI - Health-based payment and computerized patient record systems.
AB - Health care information technology is changing rapidly and dramatically. A small
but growing number of clinicians, especially those in staff and group model HMOs
and hospital-affiliated practices, are automating their patient medical records
in response to pressure to improve quality and reduce costs. Computerized patient
record systems in HMOs track risks, diagnoses, patterns of care, and outcomes
across large populations. These systems provide access to large amounts of
clinical information; as a result, they are very useful for risk-adjusted or
health-based payment. The next stage of evolution in health-based payment is to
switch from fee-for-service (claims) to HMO technology in calculating risk
coefficients. This will occur when HMOs accumulate data sets containing records
on provider-defined disease episodes, with every service linked to its
appropriate disease episode for millions of patients. Computerized patient record
systems support clinically meaningful risk-assessment models and protect patients
and medical groups from the effects of adverse selection. They also offer
significant potential for improving quality of care.
PMID- 10187227
TI - Telemedicine and information technology at the Veterans Administration Palo Alto
Health Care System: serving patient care.
PMID- 10187228
TI - Computer-prompted diabetes care.
PMID- 10187229
TI - A managed care approach to high-risk screening and case management in the
elderly.
PMID- 10187230
TI - 10 impediments to campaigns.
PMID- 10187231
TI - The art of corporate underwriting and sponsorship.
PMID- 10187232
TI - How to choose a money manager.
PMID- 10187234
TI - Are non profit fund raisers ready for the Internet?
PMID- 10187233
TI - 1999 non-profit software guide.
PMID- 10187235
TI - Why making the best call is the right call for you.
PMID- 10187236
TI - 401(k) vs. 403(b): new choices for not-for-profit companies.
PMID- 10187237
TI - Funding information technology: a missed market.
AB - Information technology is driving business and industry into the future. This is
the essence of reengineering, process innovation, downsizing, etc. Non-profits,
schools, libraries, etc. need to follow or risk efficiency. However, to get their
fair share of information technology, they need to help with funding.
PMID- 10187238
TI - From trickle down to paying up: making money talk.
PMID- 10187240
TI - Attracting physicians to underserved communities is not the solution to providing
better access to underserved communities.
PMID- 10187239
TI - Attracting physicians to underserved communities: the role of health networks.
AB - As health networks battle for additional market share and encourage additional
Medicaid HMO subscribers to use their physicians and hospitals, more health
executives are analyzing proposals of how to attract qualified doctors to
practice in poor rural or inner-city communities. Supplying more physicians to
those areas by increasing the number of medical schools, expanding the National
Health Service Corps (NHSC) program, and allowing more international medical
graduates (IMGs) to pursue residency training in the United States have been
relatively unsuccessful strategies to improve America's geographic
maldistribution of medical manpower. This article focuses on several approaches
that health networks might use to increase market penetration and at the same
time deliver enhanced health services to the underserved. Health networks may
provide eminent leadership in the overall design and governance of soundly
conceived Medicaid HMOs; strengthen existing or develop additional community
health/primary care centers; interface more effectively with local schools to
foster Medicaid HMOs for children of low-income families; and reimburse at
"premium rates" primary care physicians who practice in underserved communities.
The reluctance of physicians to practice in these areas and of middle-income and
upper-income taxpayers, and therefore elected officials, to support increased
spending or redirection of funds continue to be major barriers for health
alliances to demonstrate willingness to invest additional resources in poor inner
city and rural environments.
PMID- 10187241
TI - Obstacles to attracting physicians to underserved communities.
PMID- 10187242
TI - Work and life: the end of the zero-sum game.
AB - Most companies view work and personal life as competing priorities in a zero-sum
game, in which a gain in one area means a loss in the other. From this
traditional perspective, managers decide how their employees' work and personal
lives should intersect and often view work-life programs as just so much social
welfare. A new breed of managers, however, is trying a new tack, one in which
managers and employees collaborate to achieve work and personal objectives to
everyone's benefit. These managers are guided by three principles. The first is
to clearly inform their employees about business priorities and to encourage them
to be just as clear about personal priorities. The second is to recognize and
support their employees as whole people, not only acknowledging but also
celebrating their roles outside the office. The third is to continually
experiment with the way work gets done, looking for approaches that enhance the
organization's performance and allow employees to pursue personal goals. The
managers who are acting on these principles have discovered that conflicts
between work and personal priorities can actually be catalysts for identifying
inefficiencies at the workplace. For example, one manager and his staff found a
way to accommodate the increased workload at their 24-hour-a-day command center
while granting the staff more concentrated time off. So far, these managers have
usually been applying the principles without official sanction. But as the
business impact of their approach becomes better appreciated, the authors
predict, more and more companies will view these leaders as heralds of change.
PMID- 10187243
TI - How venture capital works.
AB - The popular mythology surrounding the U.S. venture-capital industry derives from
a previous era. Venture capitalists who nurtured the computer industry in its
infancy were legendary both for their risk taking and for their hands-on
operating experience. But today things are different, and separating the myths
from the realities is crucial to understanding this important piece of the U.S.
economy. Today's venture capitalists are more like conservative bankers than the
risk takers of days past. They have carved out a specialized niche in the capital
markets, filling a void that other institutions cannot serve. They are the linch
pins in an efficient system for meeting the needs of institutional investors
looking for high returns, of entrepreneurs seeking funding, and of investment
bankers looking for companies to sell. Venture capitalists must earn a
consistently superior return on investments in inherently risky businesses. The
myth is that they do so by investing in good ideas and good plans. In reality,
they invest in good industries--that is, industries that are more competitively
forgiving than the market as a whole. And they structure their deals in a way
that minimizes their risk and maximizes their returns. Although many
entrepreneurs expect venture capitalists to provide them with sage guidance as
well as capital, that expectation is unrealistic. Given a typical portfolio of
ten companies and a 2,000-hour work year, a venture capital partner spends on
average less than two hours per week on any given company. In addition to
analyzing the current venture-capital system, the author offers practical advice
to entrepreneurs thinking about venture funding.
PMID- 10187244
TI - Covert leadership: notes on managing professionals. Knowledge workers respond to
inspiration, not supervision.
AB - The orchestra conductor is a popular metaphor for managers today--up there on the
podium in complete control. But that image may be misleading, says Henry
Mintzberg, who recently spent a day with Bramwell Tovey, conductor of the
Winnipeg Symphony Orchestra, in order to explore the metaphor. He found that
Tovey does not operate like an absolute ruler but practices instead what
Mintzberg calls covert leadership. Covert leadership means managing with a sense
of nuances, constraints, and limitations. When a manager like Tovey guides an
organization, he leads without seeming to, without his people being fully aware
of all that he is doing. That's because in this world of professionals, a leader
is not completely powerless--but neither does he have absolute control over
others. As knowledge work grows in importance, the way an orchestra conductor
really operates may serve as a good model for managers in a wide range of
businesses. For example, Mintzberg found that Tovey does a lot more hands-on work
than one might expect. More like a first-line supervisor than a hands-off
executive, he takes direct and personal charge of what is getting done. In
dealing with his musicians, his focus is on inspiring them, not empowering them.
Like other professionals, the musicians don't need to be empowered--they're
already secure in what they know and can do--but they do need to be infused with
energy for the tasks at hand. This is the role of the covert leader: to act
quietly and unobtrusively in order to exact not obedience but inspired
performance.
PMID- 10187245
TI - The discipline of innovation.
AB - Some innovations spring from a flash of genius. But as Peter Drucker points out
in this HBR Classic, most result from a conscious, purposeful search for
opportunities. For managers seeking innovation, engaging in disciplined work is
more important than having an entrepreneurial personality. Writing originally in
the May-June 1985 issue, Drucker describes the major sources of opportunities for
innovation. Within a company or industry, opportunities can be found in
unexpected occurrences, incongruities of various kinds, process needs, or changes
in an industry or market. Outside a company, opportunities arise from demographic
changes, changes in perception, or new knowledge. These seven sources overlap,
and the potential for innovation may well lie in more than one area at a time.
Innovations based on new knowledge, of course, tend to have the greatest effect
on the marketplace. But it often takes decades before the ideas are translated
into actual products, processes, or services. The other sources of innovation are
easier and simpler to handle, yet they still require managers to look beyond
established practices. Drucker emphasizes that in seeking opportunities,
innovators need to look for simple, focused solutions to real problems. The
greatest praise an innovation can receive is for people to say, "This is
obvious!" Grandiose ideas designed to revolutionize an industry rarely work.
Innovation, like any other endeavor, takes talent, ingenuity, and knowledge. But
Drucker cautions that if diligence, persistence, and commitment are lacking,
companies are unlikely to succeed at the business of innovation.
PMID- 10187246
TI - Business marketing: understand what customers value.
AB - How do you define the value of your market offering? Can you measure it? Few
suppliers in business markets are able to answer those questions, and yet the
ability to pinpoint the value of a product or service for one's customers has
never been more important. By creating and using what the authors call customer
value models, suppliers are able to figure out exactly what their offerings are
worth to customers. Field value assessments--the most commonly used method for
building customer value models--call for suppliers to gather data about their
customers firsthand whenever possible. Through these assessments, a supplier can
build a value model for an individual customer or for a market segment, drawing
on data gathered form several customers in that segment. Suppliers can use
customer value models to create competitive advantage in several ways. First,
they can capitalize on the inevitable variation in customers' requirements by
providing flexible market offerings. Second, they can use value models to
demonstrate how a new product or service they are offering will provide greater
value. Third, they can use their knowledge of how their market offerings
specifically deliver value to craft persuasive value propositions. And fourth,
they can use value models to provide evidence to customers of their
accomplishments. Doing business based on value delivered gives companies the
means to get an equitable return for their efforts. Once suppliers truly
understand value, they will be able to realize the benefits of measuring and
monitoring it for their customers.
PMID- 10187247
TI - The new math of ownership.
AB - In 1994, when the software maker Knowledge Adventure decided to spin out a new
venture--Worlds, Incorporated--founder Bill Gross expected the worst. He had
argued with the board that it was in KA's best interests to maintain a
controlling ownership stake in Worlds, whose powerful new software technology had
enormous revenue potential. But the board prevailed, and KA took only a 20%
ownership in the new company, giving the rest to Worlds' employees. Within a
year, the company's performance had surpassed all expectations, and instead of
owning 80% of a $5 million business, KA owned 20% of a $77 million business. The
arithmetic may have been counterintuitive, but the lesson was clear. When KA let
go of Worlds and gave its employees near total ownership, the company unleashed a
new level of employee performance. That, in turn, led to the creation of economic
value that more than made up for the equity KA had surrendered. So compelling was
this "new math of ownership" that Gross founded a new company, Idealab, on this
principle. The company, which develops ideas for Internet-based businesses and
seeds the most promising ones, takes no more than a 49% equity stake in the new
ventures and gives at least 1% of ownership to each employee. For Gross, this
radical approach to ownership is the key to inspiring stellar performances. In
part, employee-owners are motivated by their potential to earn great financial
reward. But the drama of ownership, he argues, is even more important. In that
drama, employees become personally involved in the struggle to outdo the
competition and emerge victorious.
PMID- 10187248
TI - Clusters and the new economics of competition.
AB - Economic geography in an era of global competition poses a paradox. In theory,
location should no longer be a source of competitive advantage. Open global
markets, rapid transportation, and high-speed communications should allow any
company to source any thing from any place at any time. But in practice, Michael
Porter demonstrates, location remains central to competition. Today's economic
map of the world is characterized by what Porter calls clusters: critical masses
in one place of linked industries and institutions--from suppliers to
universities to government agencies--that enjoy unusual competitive success in a
particular field. The most famous example are found in Silicon Valley and
Hollywood, but clusters dot the world's landscape. Porter explains how clusters
affect competition in three broad ways: first, by increasing the productivity of
companies based in the area; second, by driving the direction and pace of
innovation; and third, by stimulating the formation of new businesses within the
cluster. Geographic, cultural, and institutional proximity provides companies
with special access, closer relationships, better information, powerful
incentives, and other advantages that are difficult to tap from a distance. The
more complex, knowledge-based, and dynamic the world economy becomes, the more
this is true. Competitive advantage lies increasingly in local things--knowledge,
relationships, and motivation--that distant rivals cannot replicate. Porter
challenges the conventional wisdom about how companies should be configured, how
institutions such as universities can contribute to competitive success, and how
governments can promote economic development and prosperity.
PMID- 10187249
TI - What makes a leader?
AB - Superb leaders have very different ways of directing a team, a division, or a
company. Some are subdued and analytical; others are charismatic and go with
their gut. And different situations call for different types of leadership. Most
mergers need a sensitive negotiator at the helm, whereas many turnarounds require
a more forceful kind of authority. Psychologist and noted author Daniel Goleman
has found, however, that effective leaders are alike in one crucial way: they all
have a high degree of what has come to be known as emotional intelligence. In
fact, Goleman's research at nearly 200 large, global companies revealed that
emotional intelligence--especially at the highest levels of a company--is the
sine qua non for leadership. Without it, a person can have first-class training,
an incisive mind, and an endless supply of good ideas, but he still won't make a
great leader. The components of emotional intelligence--self-awareness, self
regulation, motivation, empathy, and social skill--can sound unbusinesslike. But
exhibiting emotional intelligence at the workplace does not mean simply
controlling your anger or getting along with people. Rather, it means
understanding your own and other people's emotional makeup well enough to move
people in the direction of accomplishing your company's goals. In this article,
the author discusses each component of emotional intelligence and shows through
examples how to recognize it in potential leaders, how and why it leads to
measurable business results, and how it can be learned. It takes time and, most
of all, commitment. But the benefits that come from having a well-developed
emotional intelligence, both for the individual and the organization, make it
worth the effort.
PMID- 10187250
TI - Hospitals review baby-switching precautions following Virginia incident.
PMID- 10187251
TI - Two urban hospitals feature card access, cameras to secure parking areas.
PMID- 10187252
TI - Reducing neighborhood crime also improves security at Memphis hospitals.
PMID- 10187253
TI - Hospital attorney: looser visitor policies resulting in more lawsuits.
PMID- 10187254
TI - Utah hospitals: policies vary on patients, visitors who carry weapons.
PMID- 10187255
TI - Theft of expensive hospital medical equipment: how professional thieves have been
operating in Florida; what you should be doing to protect your hospital's assets.
AB - A number of Florida hospitals report they have fallen prey to thieves who are
dressing as hospital workers or service company employees and stealing expensive
medical equipment. The thefts are creating both financial loss to hospitals and
the danger that some lifesaving equipment will be missing when needed. More than
50 hospitals have been hit over the past 18 months, says Jim Kendig, incoming
president of the Florida Society for Healthcare Security and Safety
Professionals, Orlando. Are these thefts the tip of the iceberg? Logic dictates
they are taking place or will take place elsewhere, since there is nothing
different security-wise or equipment-wise about Florida hospitals compared to
those in the rest of the country that would limit criminals to one state.
Therefore, the lessons learned by Florida hospitals, as detailed in this report,
are worth heeding elsewhere.
PMID- 10187256
TI - Is your accreditation at the mercy of a surveyors' mood or agenda?
PMID- 10187257
TI - JCAHO has beefed up training and education.
PMID- 10187258
TI - JCAHO credential edges toward realization.
PMID- 10187259
TI - Keep staff smiling, and you're halfway there.
PMID- 10187260
TI - Patient satisfaction is gaining ground.
PMID- 10187261
TI - How do the generations rate their health care? Press, Gany Associates.
PMID- 10187262
TI - JCAHO restraints standards are approved.
PMID- 10187263
TI - Quality report cards market your services.
PMID- 10187264
TI - Primary care. LIZ (London Initiative Zone): a legacy for London.
AB - More than half the LIZ funding has been spent on improving GP premises and
practice staffing. But many premises are still below standard. The programme has
had no effect on reducing the number of GPs over 65 working in London. In some
areas of London the proportion has increased. Almost half (46 per cent) of
practices in London still consist of a doctor working alone. Nationally, the
figure is 30 per cent. London GPs' lists are significantly higher than in the
rest of the country. Further improvements in London's primary care are vital.
PMID- 10187265
TI - Primary care. Going solo. Interview by Jeremy Davies.
PMID- 10187266
TI - Service integration. Getting it straight.
AB - The complexity of the NHS makes it difficult to deliver a seamless service.
Aligning all the parts to the same objectives would improve patient care.
Information technology systems in the NHS are a major barrier to integration.
PMID- 10187267
TI - Hospital not negligent for granting privileges to physician with alcohol abuse
history. Domingo v. Doe.
PMID- 10187268
TI - Employment-at-will doctrine restricted further. Hausman v. St. Croix Care Center.
PMID- 10187269
TI - Dual nature of HMO examined. McEvoy v. Group Health Cooperative of Eau Claire.
PMID- 10187270
TI - Lost chance of survival case prompts consideration of ethical issues. Wendland v.
Sparks.
PMID- 10187271
TI - Georgia statute compelling submission to an HIV test upheld. Adams v. State.
PMID- 10187272
TI - Physicians' on-call arrangement does not create a joint venture. Rossi v. Oxley.
PMID- 10187273
TI - IOL (intraocular lenses) prices led by technology, payments.
PMID- 10187274
TI - GPOs, suppliers face off over effects of mergers.
PMID- 10187275
TI - Savings add up as hospital pares items from OR inventory.
PMID- 10187276
TI - Materials managers can lead the way to EDI.
PMID- 10187277
TI - Supply chain streamlining nets big savings.
PMID- 10187278
TI - Transesophageal echocardiography 2, alternatives 0.
PMID- 10187279
TI - Elder abuse and depression overlooked.
PMID- 10187280
TI - Ushering in a new era in stroke care.
PMID- 10187281
TI - Taking care of business the enterprise way.
PMID- 10187282
TI - Knowledge is power: comparative analysis software--a powerful tool for health
care.
PMID- 10187283
TI - 1998 Mammography Quality Standards Act final rule: summary of new requirements.
PMID- 10187284
TI - Applying evidence-based medicine to acute stroke.
PMID- 10187285
TI - A port in the storm: clarifying leadership expectations.
PMID- 10187286
TI - Health care reforms and developing countries--a critical overview.
AB - Although health care reforms have been implemented in both developed and
developing countries since the 1980s, there has been little discussion of the
historical, social and political contexts in which such reforms have taken place.
Health care reforms in developing countries, for instance, have been an integral
component of structural adjustment policies, yet scant attention has been paid to
these connections nor to their implications. The basic assumptions behind the
reforms, and in particular, the ideological underpinnings of health care
reorganization, need to be taken into account when considering long-term
strategies and policies to provide health services in developing countries.
PMID- 10187287
TI - Health care priorities as a problem of local resource allocation.
AB - The aim of this study was to examine attitudes to prioritization in health care
among the general public, politicians, doctors and nurses. The focus in this
paper is on the types of services from a perspective that is 'policy analytical'.
This study forms part of the wider 'Prioritization in Health Care Project'
carried out at the University of Kuopio exploring patient treatment level
prioritizations. Data were collected by a postal questionnaire in 1995. Four
groups were established for the study: (1) a general public sample of 2000
subjects, (2) a random sample of 1000 nurses, (3) a random sample of 1500 medical
doctors and (4) a sample of 2200 politicians involved in social and health care
administration. Respondents were asked to make value choices between specialized
and primary health care services in a real budget situation. One of the most
salient findings in this study was that attitudes towards priorities are context
dependent. Certain differences were observed between the groups studied. The
attitudes of the general public and nurses were quite similar, while similar
views were shared by politicians and doctors. The attitudes of the respondents
reflect well what has actually happened in Finnish health care, with the
exception of psychiatric services which have undergone drastic cuts.
PMID- 10187288
TI - The politics of the health district reform in the Republic of Benin.
AB - The analysis of health policy reform focuses mostly on the contents of reforms.
Walt and Gilson (1994) draw attention to the fact that the environmental context
as well as the actors involved are of crucial importance to the process of policy
adoption. This paper describes and analyses the process of adoption of the new
concept of so-called 'sanitary zones' in the Republic of Benin as part of the
health sector reform. The analysis of the reform is based on the examination of
documents and interviews carried out in Benin in February 1997. The main findings
show that the reasons for the specific policy choice do not emerge clearly. The
main problems identified are: the role of the hospital, the incongruous
administration, resistance against the reform and the question whether the
government actually has the political will to change. Possible solutions to these
constraints are offered in the conclusion.
PMID- 10187289
TI - Feasibility of mobile provision of health services: a study of child monitoring
centres in The Netherlands.
AB - In the Netherlands children up to the age of 4 years are regularly monitored.
Several demographic and economic developments have led to the idea of using
mobile child monitoring centres. Mobile units are expected to be flexible,
effective and efficient but little information is available about the
implications for the organization, the clients and other third parties involved.
This paper outlines an approach for assessing the feasibility of mobile child
monitoring centres. The focus is on the area Midden-Gelderland in the Netherlands
and the implications of alternative options are compared on the basis of
feasibility criteria or performance measures. The implementation of mobile units
for child monitoring appears to be feasible with respect to most performance
measures but there are also disadvantages. The approach taken proved to be a
valuable exercise since it provided detailed information on all implications. It
was decided that the mobile units would not be purchased but that some child
monitoring centres could be closed without replacing them.
PMID- 10187290
TI - Complying with the most challenging 1998 long term care pharmacy standards.
PMID- 10187292
TI - Revisions to organ procurement standard for hospitals.
PMID- 10187291
TI - Revised standard related to fire drills in business occupancies.
PMID- 10187293
TI - Role of autopsy in medical practice.
PMID- 10187294
TI - An comparative analysis into nurse job satisfaction at Kameda Medical Centre and
Mercy Hospital for Women.
PMID- 10187295
TI - Labor economics on physicians and nurses.
PMID- 10187296
TI - Local health care system utilizing the LPG (liquid propane gas) network.
AB - JAC's LPG monitoring network system is mainly provided in mountain villages.
However, by using this system, it will be possible to start a Digital Network
Program for the Elderly while maintaining superior economic feasibility and
public benefit using existing information infrastructures. This project also has
the capabilities for the creation of a fire/disaster monitoring system, as well
as a health care system by using conventional LPG monitoring systems.
Telemedicine is an option for the future, as well, by connecting medical
equipment and a tele-conferencing system.
PMID- 10187297
TI - Creating clinical path based on analysis using hospital information system.
PMID- 10187298
TI - Managed care opporties in Japan.
PMID- 10187300
TI - Labor pains. Kaiser union pact scores successes, but struggles lie ahead.
PMID- 10187299
TI - Prefectural differentials in medical expenditure for the elderly--why health care
costs for the elderly are lower in Nagano prefecture.
PMID- 10187301
TI - In search of evidence. Calif. system adopts clinical guidelines, finds quality
approach is cost-effective.
PMID- 10187302
TI - Opening the floodgates? Observers debate effects of expanding plans' access.
PMID- 10187303
TI - Speed demons. New generation of CTs faster and far more expensive.
PMID- 10187304
TI - The strong, silent type. Low-profile Midwest system posts impressive numbers.
PMID- 10187305
TI - Going public. Joint Commission launches radio ad campaign.
PMID- 10187306
TI - Specialists sue HCFA over payment.
PMID- 10187307
TI - Union fight continues. NLRB takes testimony on unions for physicians.
PMID- 10187308
TI - Seizing the initiative. Clinton, Democrats think electorate showed it's ready.
PMID- 10187309
TI - HCFA: PROs should probe billing fraud.
PMID- 10187310
TI - Detailing embezzlement. Report shows how former execs bilked N.J. system.
PMID- 10187311
TI - Groups offer tools to study satisfaction with care settings.
PMID- 10187312
TI - Competitive disadvantage? Mont. system acuses competitors of skirting state law.
PMID- 10187313
TI - Embattled Optima awaits future.
PMID- 10187314
TI - Abandoning ship. IHS, post-acute chains join other home-care dropouts.
PMID- 10187315
TI - It's a wrap, sort of. After purchases from Columbia, real work begins.
PMID- 10187316
TI - No end in sight. Five-year probe of Columbia, Quorum keeps growing.
PMID- 10187317
TI - Hospital hit for hiring AHERF physicians.
PMID- 10187318
TI - It's called desire. Study shows that fastest-growing hospitals execute their best
laid plans.
PMID- 10187319
TI - The feds pay more. Premiums twice those of private sector--study.
PMID- 10187320
TI - Ratio ruckus. Nurses at Milwaukee hospital angry over staffing change.
PMID- 10187321
TI - Healthcare goes to school with kids in Denver County.
PMID- 10187322
TI - Focus on end-of-life care. Foundation awards grants to improve care programs.
PMID- 10187323
TI - More going bloodless. Transfusion-free surgery seen as safer, cheaper
alternative, with faster recoveries.
PMID- 10187324
TI - Voters back pot rights. Medicinal use of marijuana approved in four states.
PMID- 10187325
TI - Understaffed in Calif. State report urges added ER capacity for flu season.
PMID- 10187326
TI - Assigning the blame. Medicare risk pullouts have everyone pointing fingers.
PMID- 10187327
TI - Taking physicians captive. Reducing doctor's independence aligns incentives,
creates financial leverage.
PMID- 10187328
TI - To be, or not to be? Medicare pilot project moves ahead; questions remain.
PMID- 10187329
TI - OK, we're not-for-profit, but ... show us the money!
AB - For-profits aren't the only ones who like to deal. As recent transactions show,
small fortunes can be had in merger and affiliation talks with not-for-profit
healthcare systems. Although rarely publicized, it isn't uncommon to find
explicit promises of cash or capital investments hidden deep in agreement for
merger, affiliation or mergerlike partnership deals with not-for-profits.
PMID- 10187330
TI - Twin Cities: where HMOs are welcome. Area has already gone through process that
rest of nation is only beginning.
PMID- 10187331
TI - A man of many places. CHA chief its the road to spread gospel of Catholic
healthcare. Interview by Deanna Bellandi.
PMID- 10187332
TI - Spending slows in Medicare, elsewhere.
PMID- 10187333
TI - Go ahead and merge, but ... Montana adds conditions to insurers' controversial
deal.
PMID- 10187334
TI - Windfall for hospitals. California OKs trust fund's plan to dole out money.
PMID- 10187335
TI - Hospital, PPM to build facility.
PMID- 10187336
TI - MedPartners fallout. PPM's decision to exit may propel docs toward hospitals.
PMID- 10187337
TI - Market drives Alliance. New Orleans hospitals won't merge until the time is
right.
PMID- 10187338
TI - See you in court. Damage inflicted by the Y2K bug threatens to become a dream for
litigators but a nightmare for healthcare executives.
AB - Most hospitals and health systems perceive and treat the year-2000 faulty
computer code as a technical problem, but it is a high-level management problem.
If hospitals don't start preparing comprehensively, they will face a host of
consequences. Experts say spillover will extend into business issues, finances
and liability. But providers must choose their most important priorities and
develop contingency plans.
PMID- 10187339
TI - Cash flow a likely Y2K casualty.
PMID- 10187340
TI - The superbug battle. One hospital duels drug-resistant infections with an all
encompassing program.
PMID- 10187341
TI - Pie in the sky? Hospitals like the idea of gain sharing but not its pitfalls.
PMID- 10187342
TI - Headed for an audit? HCFA taking a closer look at 'provider-based' facilities.
PMID- 10187343
TI - Hospital outpatient PPS proposed rule published.
PMID- 10187344
TI - Focus on fraud and abuse. How medical groups can avoid fraudulent billing
practices.
PMID- 10187345
TI - How to really make a killing in health care. The rewards to whistle blowers soar.
PMID- 10187346
TI - Return of a killer. Phages may once again fight tough bacterial infections.
PMID- 10187347
TI - Juggling rights and remedies. New rules are coming for treating the mentally ill
fairly in clinical trials.
PMID- 10187348
TI - Y2K doesn't bug them. Europe trails the United States in dealing with the year
2000 computer problem.
PMID- 10187349
TI - Miracle vaccines. Advances in genetic engineering are spawning a new generation
of powerful disease fighters.
PMID- 10187350
TI - Doing Ritalin right. Sure, it works--but there are big flaws in the way it's
being given.
PMID- 10187351
TI - Going outside the medical mainstream. Can 42 percent of Americans be wrong?
PMID- 10187352
TI - Hope for the heart. Using genes to help form new blood vessels.
PMID- 10187353
TI - First UK installation of new medical waste treatment system.
PMID- 10187354
TI - The disposal of healthcare risk/clinical waste in the Island of Ireland.
PMID- 10187355
TI - Outcomes management. Pioneer in automated patient data gets dramatic results.
PMID- 10187356
TI - Workflow automation. The next step: automating workflows to reduce errors,
duplication, and rework.
PMID- 10187357
TI - Hang in there! Quick takes on Y2K.
AB - Cliffhangers in movies are great fun. But not in real life. Think Y2K. If you
haven't scripted a way to beat the millennium bug, there are workable solutions
that can be created in six months. Here's how to begin production: Prioritize
activities, expenditures and resources, and apply them to the most vital problems
first.
PMID- 10187358
TI - Do the right thing. A corporate compliance program aims to keep Promina out of
the spotlight.
PMID- 10187359
TI - Making the grade. Train new workers, OSHA says, but how? Check out these case
studies.
PMID- 10187360
TI - True cost. Get the big picture with ABM.
PMID- 10187361
TI - He said, she said. Venus meets Mars at work.
PMID- 10187362
TI - How do you price a used device?
PMID- 10187363
TI - Changing gear. Home care providers look to lighten their load.
PMID- 10187364
TI - Stats. Guess what keeps the top brass up at night.
PMID- 10187365
TI - The sweet sound of success.
AB - Accommodating workers with disabilities doesn't have to be daunting, this
entrepreneur cum cookie maker discovered. Gimmee Jimmy's recipe: A batch of
ingenuity and a sprinkling of money.
PMID- 10187366
TI - Health reform '99: a modest proposal.
PMID- 10187367
TI - The new direction in disability management. Tactical teamwork.
PMID- 10187368
TI - The Medicare HMO disappearing act.
PMID- 10187369
TI - America's healthiest companies. A close-up of this year's recipients of the C.
Everett Koop National Health Award reveals their winning strategies.
PMID- 10187370
TI - Cost is still king. The D&T/B&H Employer Managed Care Survey.
PMID- 10187371
TI - Coping with COBRA.
PMID- 10187372
TI - Data watch. The high price of modifiable health risks.
PMID- 10187373
TI - Part II: What do employers mean by "value"?
AB - With health care costs clearly on the rise again, and First Generation Managed
Care having matured itself into market gridlock, it is inevitable that there will
be a second "employer" revolt. As long as private purchasers do not see
organizations fully focused on "value" as they see it, they will not be content
with rising costs as "unavoidable". And whereas I do not believe we will see the
double digit increases of the 1970's and 80's, consistent annual increases of
greater than 5% (or 2-3 times the general inflation rate) will become a major
problem, particularly when the current economic expansion ends, and top-line
growth in revenues and profits outside the health care sector are once again
under pressure. The timing of this second employer revolution is anyone's guess,
but it is likely to occur with lightning speed on the heels of a major and
sustained correction in the global market. Employers will be looking to move
volume to organizations that can offer the best value. Integrated health systems
have the potential to become these organizations but, they have significant
hurdles to overcome. However, from the private sector point of view, if doctors
are willing to listen, learn a new language and become committed to
accountability and measurement, employers innately believe that those closest to
the "customer" (i.e. patients) are best able to manage. Whether, provider systems
can rise to this challenge is unclear. But the stakes, for physicians, purchasers
and ultimately patients, have never been higher. And employers, as a group, are
hopeful that these organizations can live up to their promise.
PMID- 10187374
TI - The integration of Helix Health.
PMID- 10187375
TI - Regulating managed care coverage: a new direction for health-planning agencies.
AB - The article focuses on the role of health planning agencies in the context of
managed care. The author argues that health planning agencies can be redirected
toward assessment of managed care plans. Planning entities can be used to
evaluate the viability of managed care markets taking into account societal,
financial and medical considerations.
PMID- 10187376
TI - Boards of directors under fire: an examination of nonprofit board duties in the
health care environment.
AB - Attorney Ono presents a detailed discussion of fiduciary duty principles as
applied to the directors of nonprofit health care corporations in the current
health care environment. The article reviews general corporate responsibilities,
the implication of the taxpayer's Bill of Rights 2, the care of In re Caremark
International Inc. Derivative Litigation and particular issues faced by boards in
nonprofit conversions.
PMID- 10187377
TI - Responsibilities of directors of not-for-profit corporations faced with sharing
control with other nonprofit organizations in health industry affiliations: a
commentary on legal and practical realities.
AB - This article concerns the legal responsibilities of not-for-profit corporation
directors in merges and affiliations with other not-for-profits. The article
considers three sets of legal duties board members have, ancillary contractual
obligations, madatory statutes and procedural laws, and contextual legal duties.
PMID- 10187378
TI - Recent changes to the Internal Revenue Code may require tax-exempt hospitals to
restructure ownership of certain activities.
AB - This article by attorney mandarino explores the implications of a 1997 change in
the Internal Revenue Code affecting tax-exempt hospitals which run or operate for
profit businesses. The piece explores the application of prior law to hospital
ownership of for-profit ventures and continues on to review the implications of
the 1997 amendment, particularly on existing structures. The article conclude
with suggestions to avoid applications of the amended section.
PMID- 10187379
TI - Federal regulation comes to private health care financing: the group health
insurance provisions of the Health Insurance Portability and Accountability Act
of 1996.
AB - Attorney Rovner presents a very detailed accounting of the impacts of the Health
Insurance Portability and Accountability Act as it relates to group health
insurance including provisions that concern pre-existing conditions, special
enrollment rights, premium discrimination, maternity lengths of stay, parity for
mental health benefits and small groups coverage. The article concludes with a
discussion of the federalism question as it relates to regulation of private
market health financing.
PMID- 10187380
TI - A look back at the year in health law.
AB - The Bennett article takes us back to 1997 and reviews key legislators,
regulations and judicial developments in Medicare, antitrust, tax and ERISA, all
of which greatly impact the practice of health law.
PMID- 10187381
TI - Managed care at the crossroads: can managed care organizations survive government
regulation?
AB - Attorneys Brown and Hartung provide a comprehensive overview of the development
and structural components of managed health care plans. The article discusses the
state regulatory controls affecting managed care including Patient Protection
Acts, mandated benefit provisions, any willing provider laws, and consumer access
provisions. The article considers liability problems facing managed care
organizations, in particular liabilities which arise from utilization and medical
review discussions as well as gag clauses and financial incentive arrangements.
The authors also review relevant federal regulatory initiatives.
PMID- 10187382
TI - The states, Congress, or the courts: who will be first to reform ERISA remedies?
AB - Curtis Rooney's article reviews the ERISA law and it relationship to managed
care. The piece continues with a review of the relevant preremption provisions
and a extentivsive discussion of related U.S. Supreme Court decisions. The author
discusses malpractice and design liabilities. The article concludes with a
discussion of reform initiatives directed toward the ERISA preemption and damage
provisions.
PMID- 10187383
TI - Medical devices; humanitarian use of devices--FDA. Final rule.
AB - The Food and Drug Administration (FDA) is issuing a final rule amending the
regulations governing humanitarian use devices (HUD's). These amendments are
being made to implement provisions of the Federal Food, Drug, and Cosmetic Act
(the act) as amended by the Food and Drug Administration Modernization Act of
1997 (FDAMA).
PMID- 10187384
TI - Medical devices; exemptions from premarket notification; class II devices--FDA,
Final rule.
AB - The Food and Drug Administration (FDA) is codifying the exemption from premarket
notification of all 62 class II (special controls) devices listed as exempt in a
January 21, 1998, Federal Register notice, subject to the limitations on
exemptions. FDA has determined that for these exempted devices, manufacturers'
submissions of premarket notifications are unnecessary to provide a reasonable
assurance of safety and effectiveness. These devices will remain subject to
current good manufacturing practice (CGMP) regulations and other general
controls. This rulemaking implements new authorities delegated to FDA under the
Food and Drug Administration Modernization Act (FDAMA).
PMID- 10187385
TI - Civilian Health and Medical Program of the Uniformed Services (CHAMPUS); state
victims of crime compensation programs; voice prostheses--DoD. Final rule.
AB - This final rule establishes CHAMPUS as primary payer to State Victims of Crime
Compensation Programs; and voice prostheses as a CHAMPUS benefit.
PMID- 10187386
TI - TRICARE/CHAMPUS: FY99 DRG updates--DoD. Notice of DRG revised rates.
AB - This notice describes the changes made to the TRICARE/CHAMPUS DRG-based payment
system in order to conform to changes made to the Medicare Prospective Payment
System (PPS). It also provides the updated fixed loss cost outlier threshold,
cost-to-charge ratios and the Internet address for accessing the updated adjusted
standardized amounts, DRG relative weights, and beneficiary cost-share per diem
rates to be used for FY 1999 under the TRICARE/CHAMPUS DRG-based payment system.
PMID- 10187387
TI - Quality mammography standards--FDA. Proposed rule.
AB - The Food and Drug Administration (FDA) is proposing to amend its regulations
governing mammography that published in a document entitled "Quality Mammography
Standards." The purpose of these amendments is to eliminate a conflict between
the mammography regulations, which must be followed by all facilities performing
mammography, and FDA's Electronic Product Radiation Control (EPRC) performance
standards, which establish radiation safety performance requirements for x-ray
units, including mammographic systems.
PMID- 10187388
TI - General hospital and personal use devices: proposed classification of liquid
chemical sterilants and general purpose disinfectants--FDA. Proposed rule.
AB - The Food and Drug Administration (FDA) is proposing to classify both liquid
chemical sterilants intended for use as the terminal step in processing critical
and semicritical medical devices prior to patient use, and general purpose
disinfectants intended to process noncritical medical devices and equipment
surfaces. Under the proposal, liquid chemical sterilants would be classified into
class II (special controls) and general purpose disinfectants would be classified
into class I (general controls). FDA also proposes to exempt general purpose
disinfectants from the premarket notification requirements. The agency is
publishing in this document the recommendations of the General Hospital and
Personal Use Devices Panel (the Panel) regarding the classification of these
devices. After considering public comments on the proposed classification, FDA
will publish a final regulation classifying these devices. This action is being
taken to establish sufficient regulatory controls that will provide reasonable
assurance of the safety and effectiveness of these devices.
PMID- 10187389
TI - Medical devices containing materials derived from animal sources (except for in
vitro diagnostic devices), guidance for FDA reviewers and industry; availability-
FDA. Notice.
AB - The Food and Drug Administration (FDA) is announcing the availability of the
guidance entitled "Medical Devices Containing Materials Derived From Animal
Sources (Except for In Vitro Diagnostic Devices), Guidance for FDA Reviewers and
Industry." This guidance is intended to provide recommendations for information
that is to be included in premarket submissions--investigational device exemption
(IDE), premarket approval application (PMA), and 510(k) submissions for medical
devices that either contain or are exposed to animal-derived materials during
manufacturing.
PMID- 10187390
TI - Mutual recognition of pharmaceutical good manufacturing practice inspection
reports, medical device quality system audit reports, and certain medical device
product evaluation reports between the United States and the European Community-
FDA. Final rule.
AB - The Food and Drug Administration (FDA) is amending its regulations pursuant to an
international agreement between the United States and the European Community
(EC). The agreement is entitled "Agreement on Mutual Recognition Between the
United States and the European Community (MRA). Under the terms of the agreement,
the importing country authority may normally endorse good manufacturing practice
(GMP) inspection reports for pharmaceuticals provided by the exporting authority
determined by the importing authority to have an equivalent regulatory system.
Likewise, the importing country authority may normally endorse medical device
quality system evaluation reports and certain medical device product evaluation
reports by conformity assessment bodies (CAB's) determined by the importing
country authority to have equivalent assessment procedures. FDA is taking this
action to enhance its ability to ensure the safety and effectiveness of
pharmaceuticals and medical devices through more efficient and effective
utilization of its regulatory resources. The proposed rule which published in the
Federal Register on April 10, 1998 (63 FR 17744), carried an incorrect docket
number in its heading. This final rule carries the correct docket number.
PMID- 10187391
TI - Per diem for nursing home care of veterans in state homes--VA. Proposed rule.
AB - This document proposes to revise regulations setting forth a mechanism for paying
per diem to State homes providing nursing home care to eligible veterans. The
intended effect of the proposed regulations is to ensure that veterans receive
high quality care in State homes.
PMID- 10187392
TI - VA acquisition regulations: simplified acquisition procedures for health care
resources--VA. Proposed rule.
AB - This document proposes to amend the Department of Veterans Affairs Acquisition
Regulations (VAAR) to establish simplified procedures for the competitive
acquisition of healthcare resources, consisting of commercial services or the use
of medical equipment or space, pursuant to 38 U.S.C. 8151-8153. Presently, the
VAAR does not contain simplified procedures. In the absence of such procedures,
the Department of Veterans Affairs (VA) follows the Federal Acquisition
Regulation (FAR) and the current VAAR. Public Law 104-262, the Veterans' Health
Care Eligibility Reform Act of 1996, authorized VA to prescribe simplified
procedures for the procurement of health-care resources. This proposed rule
prescribes those procedures.
PMID- 10187393
TI - Ryan White Care Act requirement--Secretary's determination on HIV testing of
newborns--CDC. Notice and request for comments.
AB - Section 2626 of P.L. 104-146 (42 U.S.C. 300ff-34), the "Ryan White CARE Act
Amendments of 1996", includes a requirement for the Secretary of HHS to make a
determination whether a set of activities prescribed in section 2627 of the
Public Health Service (PHS) Act (42 U.S.C. 300ff-35), have become routine
practice in the United states. In making this determination, the Secretary is
required to consult with the States and other public or private entities that
have knowledge or expertise relevant to the determination. The purpose of this
notice is to request comments from States and such other public or private
entities with knowledge or expertise relevant to the practice of activities (1)
through (4) in section 2627 of the PHS Act (42 U.S.C. 300ff-35). After
consideration of comments submitted the CDC will provide a summary of comments
received to the Secretary as part of the process leading to the Secretary's
determination required by Section 2626 of the PHS Act (42 U.S.C. 300ff-34).
PMID- 10187394
TI - Approval of an alternative requirement of the Mammography Quality Standards Act;
availability--FDA. Notice.
AB - The Food and Drug Administration (FDA) is announcing the availability of a
document entitled "Approval of an Alternative Requirement of the Mammography
Quality Standards Act" (the MQSA). The MQSA final regulations require that the
collimation of the mammography unit permit the x-ray field to extend to or beyond
the edges of the image receptor. FDA has approved a request from General Electric
(GE) Medical Systems for an alternative to the MQSA requirement to apply to GE
Senographe mammographic systems.
PMID- 10187395
TI - Protection of human subjects: categories of research that may be reviewed by the
Institutional Review Board (IRB) through an expedited review procedure--FDA.
Notice.
AB - On November 10, 1997, the Food and Drug Administration (FDA), in consultation
with the Office for Protection from Research Risks (OPRR) at the National
Institutes of Health, requested written comments relating to the proposed
republication of the list that identifies certain research activities involving
human subjects that may be reviewed by the Institutional Review Board (IRB)
through the expedited review procedure authorized in 21 CFR 56.110. The comment
period closed on March 10, 1998. FDA and OPRR received a combined total of 108
comments. After a review of the comments, FDA and OPRR are now simultaneously
publishing identical revised lists of categories of research activities that may
be reviewed by the IRB through the expedited review procedure.
PMID- 10187396
TI - Unified agenda of federal regulatory and deregulatory actions--HHS. Semiannual
regulatory agenda.
AB - The President's Executive Order 12866 and the Regulatory Flexibility Act of 1980
require the semiannual publication of an agenda which summarizes all current,
projected, and recently completed rulemakings of the Department. The agenda
informs the public about regulatory actions that are under development within the
components of the Department, and it provides all concerned with the opportunity
to participate in this work at an early stage. The last such agenda was published
on April 27, 1998.
PMID- 10187397
TI - Unified agenda of federal regulatory and deregulatory actions--VA. Semiannual
regulatory agenda.
AB - This agenda announces the regulations that the Department of Veterans Affairs
(VA) will have under development or review during the 12-month period beginning
October 1998. The purpose in publishing the Department's regulatory agenda is to
allow all interested persons the opportunity to participate in VA's regulatory
planning.
PMID- 10187398
TI - Medical devices; exemption from premarket notification and reserved devices;
Class I--FDA. Proposed rule.
AB - The Food and Drug Administration (FDA) is proposing to amend its classification
regulations to designate class I devices that are exempt from the premarket
notification requirements, subject to certain limitations, and to designate those
class I devices that remain subject to premarket notification requirements under
the new statutory criteria for premarket notification requirements. The devices
FDA is proposing to designate as exempt do not include class I devices that have
been previously exempted by regulation from the premarket notification
requirements. This action is being taken under the Federal Food, Drug, and
Cosmetic Act (the act), as amended by the Medical Device Amendments of 1976 (the
1976 amendments), the Safe Medical Devices Act of 1990 (SMDA), and the Food and
Drug Administration Modernization Act of 1997 (FDAMA). FDA is taking this action
in order to implement a requirement of FDAMA.
PMID- 10187399
TI - Notice of availability of funds; cooperative agreement for national programs to
prevent HIV infection and other important health problems among youth strengthen
coordinated school health programs--CDC.
PMID- 10187400
TI - Medicare program; hospice wage index; corrections--HCFA. Notice; correction
notice.
AB - In the October 5, 1998 issue of the Federal Register (63 FR 53446), we published
a notice announcing the annual update to the hospice wage index. The wage index
is used to reflect local differences in wage levels. That update was effective
October 1, 1998 and is the second year of a 3-year transition period. This notice
corrects errors made in that document.
PMID- 10187401
TI - Medicare program; prospective payment system for hospital outpatient services;
extension of comment period--HCFA. Notice of extension of comment period for
proposed rule.
AB - This notice extends the comment period for a proposed rule published in the
Federal Register on September 8, 1998, (63 FR 47552). In that rule, as required
by sections 4521, 4522, and 4523 of the Balanced Budget Act of 1997, we proposed
to eliminate the formula-driven overpayment for certain outpatient hospital
services, extend reductions in payment for costs of hospital outpatient services,
and establish in regulations a prospective payment system for hospital outpatient
services (and for Medicare Part B services furnished to inpatients who have no
Part A coverage.) The comment period is extended for 60 days.
PMID- 10187402
TI - Medicare program; update of ratesetting methodology, payment rates, payment
policies, and the list of covered procedures for ambulatory surgical centers
effective October 1, 1998; extension of comment period--HCFA. Notice of extension
of comment period for proposed rule.
AB - This notice extends the comment period for the third time on a proposed rule
published in the Federal Register on June 12, 1998, (63 FR 32290). In that rule
we proposed to make various changes, including changes to the ambulatory surgical
center (ASC) payment methodology and the list of Medicare covered procedures. The
comment period is extended for 60 days.
PMID- 10187403
TI - MacDill 65 demonstration of military managed care--DoD. Notice of demonstration
project.
AB - This notice is to advise interested parties of a demonstration project in which
DoD will enroll up to 2,000 Medicare-eligible military retirees at MacDill Air
Force Base to primary care managers. The MacDill 65 demonstration project seeks
to show that a DoD-operated program can provide primary health care services to
beneficiaries eligible for both military health care and Medicare more
effectively and efficiently than under the current DoD-operated system. In this
project, DoD will grant enrollees in the program priority access to primary
health care at MacDill in exchange for their agreement to receive all of their
primary health care from MacDill AFB. Additional services, available at the
military treatment facility at MacDill AFB, will be granted to these enrollees at
a higher priority than that granted to other retirees and their family members
not enrolled in TRICARE Prime. Funding for the demonstration for care provided
will come from an additional $2 million per year over the current level of DoD
expenditures on care provided to the MacDill AFB Medicare-eligible population.
Claims for care provided to enrollees outside the MTF will be submitted to
Medicare on a fee-for-service basis by the civilian provider. At the end of the
project, DoD will conduct an analysis of the benefits and costs of the program.
DoD will conduct the demonstration over three years, from October 1, 1998, to
September 30, 2001. This demonstration project is being conducted under the
authority of 10 USC 1092.
PMID- 10187404
TI - TRICARE: the Civilian Health and Medical Program of the Uniformed Services
(CHAMPUS); specialized treatment services (STS) program--DoD. Notice.
AB - This notice is to advise interested parties that Naval Hospital Jacksonville
(NAVHOSPJAX), Florida, has been designated a regional Specialized Treatment
Services facility (STSF) for total joint replacement. The application for this
STSF designation was submitted by NAVHOSPJAX and approved by the Assistant
Secretary of Defense (Health Affairs). The Lead Agent for TRICARE Region 3 will
oversee that the STSF maintains the quality and standards required for
specialized treatment services. This designation covers the following Diagnostic
Related Groups: 209--Major Joint and Limb Reattachment Procedures of Lower
Extremity 491--Major Joint and Limb Reattachment Procedures of Upper Extremity
DoD beneficiaries who reside in the NAVHOSPJAX STS Catchment Area must be
evaluated by NAVHOSPJAX before receiving TRICARE/CHAMPUS cost sharing for
procedures that fall under the above Diagnostic Related Groups, in accordance
with TRICARE/CHAMPUS Nonavailability Statement policy. Travel and lodging for the
patient and, if stated to be medically necessary by a referring physician, for a
nonmedical attendant, will be reimbursed by NAVHOSPJAX in accordance with the
provision of the Joint Federal Travel Regulation. Although evaluation in person
is preferred, it is possible to conduct the evaluation telephonically if the
patient is unable to travel to NAVHOSPJAX. If the procedures cannot be performed
at NAVHOSPJAX, Humana Military Healthcare Services will provide a medical
necessity review prior to issuance of a Nonavailability Statement or other
similar authorizations. The NAVHOSPJAX STSF Catchment Area includes zip codes
within TRICARE Region 3 that fall within a 200-mile radius South and West of
NAVHOSPJAX.
PMID- 10187405
TI - TRICARE; the Civilian Health and Medical Program of the Uniformed Services
(CHAMPUS); specialized treatment services (STS) program--DoD. Notice.
AB - This notice is to advise interested parties that Dwight D. Eisenhower Army
Medical Center (EAMC), Fort Gordon, Georgia, has been designated a regional
Specialized Treatment Services facility (STSF) for Neurosurgery, Orthopedic
Surgery, General Surgery, Peripheral Vascular Surgery, and Head and Neck Surgery.
The application for this STSF designation was submitted by the Lead Agent for
TRICARE Region 3 and approved by the Assistant Secretary of Defense (Health
Affairs). The Lead Agent will oversee that the STSF maintains the quality and
standards required for specialized treatment services. This designation covers
the following Diagnostic Related Groups: 001--Craniotomy, Age Greater than 17,
Except for Trauma 004--Spinal Procedures 049--Major Head and Neck Procedures 191-
Pancreas, Liver and Shunt Procedures with CC 110--Major Cardiovascular Procedures
with CC 111--Major Cardiovascular Procedures without CC 286--Adrenal and
Pituitary Procedures 209--Major Joint and Limb Reattachment Procedures of Lower
Extremity 491--Major Joint and Limb Reattachment of Upper Extremity DoD
beneficiaries who reside in the EAMC STS Catchment Area must be evaluated by EAMC
before receiving TRICARE/CHAMPUS cost sharing for procedures that fall under the
above Diagnostic Related Groups, in accordance with TRICARE/CHAMPUS
Nonavailability Statement policy. Travel and lodging for the patient and, if
stated to be medically necessary by a referring physician, for a nonmedical
attendant, will be reimbursed by EAMC in accordance with the provisions of the
Joint Federal Travel Regulation. Although evaluation in person is preferred, it
is possible to conduct the evaluation telephonically if the patient is unable to
travel to EAMC. If the procedure cannot be performed at EAMC, Humana Military
Healthcare Services will provide a medical necessity review prior to issuance of
a Nonavailability Statement or other similar authorizations. The EAMC STSF
Catchment Area is defined by zip codes in the Defense Medical Information System
STS Facilities Catchment Area Directory. The Catchment Area includes zip codes
within TRICARE Region 3 that fall within a 200-mile radius of EAMC.
PMID- 10187406
TI - TRICARE: the Civilian Health and Medical Program of the Uniformed Services
(CHAMPUS); specialized treatment services (STS) program--DoD. Notice.
AB - This notice is to advise interested parties that Brooke Army Medical Center
(BAMC) and Wilford Hall Medical Center (WHMC), hereinafter referred to as
Destination San Antonio, have been designated the Regional Specialized Treatment
Service facilities (STSFs) for DRGs 1, 3, 4, 49, 104-107, 110-111, 191, 209, 491,
286, and 357. The application for the STSF designation was submitted by the Lead
Agency for TRICARE Region 6 and approved by the Assistant Secretary of Defense
(Health Affairs). The Lead Agent will oversee that the STSFs maintain the quality
and standards required for specialized treatment services. DoD beneficiaries
residing within a 200-mile radius of Destination San Antonio facilities falling
into the above patient category must be evaluated by Destination San Antonio
staff before receiving care for these DRGs under direct military care or
TRICARE/CHAMPUS cost sharing. Travel and lodging for the patient and, if stated
to be medically necessary by a referring physician, for a nonmedical attendant,
will be reimbursed by Destination San Antonio facility in accordance with the
provisions of the Joint Federal Travel Regulation. Although evaluation in person
is preferred, it is possible to conduct the evaluation telephonically if the
patient is unable to travel to a Destination San Antonio facility. If the care
for these DRGs cannot be performed at the Destination San Antonio facilities, the
TRICARE Managed Care Support Contractor for Region 6 will provide a medical
necessity review prior to issuance of an Inpatient Care Authorization or Non
availability Statement.
PMID- 10187408
TI - Groups lose legislative battle on nontherapy ancillary pass-through; effort
shifts to development of index.
PMID- 10187407
TI - HCFA issues instructions on Medicare outpatient therapy payments; Part B caps
will apply to individual providers.
PMID- 10187409
TI - Five strategies for managing drug costs under PPS.
PMID- 10187410
TI - Mix of national, local benchmarks are critical for perspective.
AB - You need a range of national and local data to make your benchmarking successful:
national to help you keep your finger on the pulse and local to help you
differentiate your service. Never rely on national averages. Instead, find a
better performer and study its processes to find out the reasons behind the data.
No matter what your local situation is, you always can learn from someone else,
particularly if they're different from you.
PMID- 10187411
TI - Health plans that disclose also perform better.
AB - The gap between top- and bottom-performing plans in NCQA's State of Managed Care
Quality report remains enormous. For example, beta-blocker treatment rates range
from 52% to 92%. The report includes data on 292 health plans on effectiveness of
care and member satisfaction measures. Fewer health plans were willing to release
their performance data publicly this year.
PMID- 10187412
TI - Hospital cuts unscheduled returns to special care.
PMID- 10187413
TI - Best practices for world-class call centers.
AB - Quality, not quantity, counts more in performance measures for best-practice call
centers. Spend money on effective upfront training to save later through
increased employee and customer loyalty. Give structured feedback and strong
internal support to call-center representatives.
PMID- 10187414
TI - Group to identify quality measures for kids.
AB - The Children's Health Measurement Initiative will enable consumers, purchasers,
and providers to evaluate and improve the quality performance of pediatric care.
Current measures for children are limited to utilization issues like numbers of
well-child visits and immunizations. Priorities include adolescent risk
reduction, promoting healthy development of small children, and care for children
with chronic illnesses.
PMID- 10187415
TI - The effects of managed care on the retail distribution of pharmaceuticals.
AB - The growth of managed care has resulted in substantial changes in the retail
channel of distribution for pharmaceuticals. Community pharmacies' numbers and
profit margins have declined, and marketshare has shifted to mail-service
pharmacies as MCOs and pharmacy benefit managers have dictated reimbursement
terms. Community pharmacies have consolidated to increase negotiating power and
efficiency and have become more involved in direct patient care. The success of
both MCOs and community pharmacies may depend on their ability to provide
cooperative services that improve patients' health outcomes.
PMID- 10187416
TI - Stats & facts. Utilizing physician extenders.
PMID- 10187417
TI - Major depression.
PMID- 10187418
TI - Recognizing and reducing physician stress in managed care environments.
AB - Stress management has become an issue for managed care medical directors, quality
improvement coordinators, and others affected by the changing face of the health
care industry and their role in it. This article offers insight on how to foster
better ties with staff and network physicians, and to develop tools that could
alleviate professional stress.
PMID- 10187419
TI - The role of direct-to-consumer advertising.
PMID- 10187420
TI - Performance measurement and/or program management?
PMID- 10187421
TI - District court rules on Texas Health Care Liability Act.
AB - The Health Care Liability Act, recently enacted in Texas, allows individuals to
sue health insurance carriers, HMOs, and other managed care entities under
certain circumstances. This article discusses the implications of the Act for
managed care plans, including ERISA preemption.
PMID- 10187422
TI - Can consumers understand managed care report cards?
AB - Research has not adequately assessed the effect of education, ethnicity, and
culture on the ability of consumers to read and understand HMO report cards. Data
on those three issues suggest that large segments of the population do not have
the reading proficiency to understand and use current report cards. Without
incorporating such factors, reports cards will not achieve broad use within the
general population, but will only meet the needs of those consumers whose values
are consistent with those of the report card developers.
PMID- 10187423
TI - Information technology, best practices, and care management: Part I.
AB - Web-enabled technologies are swiftly becoming popular in all walks of life-
health care included. New health care applications are blossoming every week,
creations that promise to drastically change the efficiency of managed care
systems. In this first installment of a two-part series, the author describes
some of the innovative changes that are occurring today.
PMID- 10187424
TI - Expect pressure for payment cuts from Medicare risk plans.
PMID- 10187425
TI - Providers create coordinated care system to help cover Birmingham's uninsured.
AB - Providers strive to manage the uninsured themselves. Providers in Birmingham, AL,
have partnered with a public hospital to better manage patients with no insurance
coverage, and in the process have spread the cost of uncompensated care. See how
Cooper Green Hospital leads the way.
PMID- 10187426
TI - New capitation survey reveals declines in provider payment, lower Medicare
utilization.
AB - Data File: Here's an analysis of some exclusive data from the 1998 Capitation
Survey, conducted by the publishers of PSCR. Responding providers report declines
or skimpy increases in their Medicare risk payments, while Medicare utilization
decreased compared with last year.
PMID- 10187427
TI - Administrative benchmarks for Medicare, Medicaid HMOs.
AB - Plus, check out benchmark data on Medicare and Medicaid administrative costs.
Every provider knows that HMOs take a slice of the Medicare or Medicaid premium
for their administrative costs before they determine provider capitation. But how
much does administration really cost? Here's some PMPM data from a study by the
Sherlock Company.
PMID- 10187428
TI - Can you meet information needs of 'new seniors' in Medicare risk?
AB - Get ready for a new kind of senior. There's a new senior consumer emerging who is
demanding health care-related information. Learn how Medicare risk providers can
keep seniors happy in their plans and how to communicate with them.
PMID- 10187429
TI - Hospital and physician partnership succeeds with Medicare managed care.
PMID- 10187430
TI - Plan ahead to improve surgical outcomes for the elderly.
PMID- 10187431
TI - National program aims to set standards for managed senior care.
PMID- 10187432
TI - Tie one on.
PMID- 10187433
TI - Terrorism. Part 1: Calibrating your risks and response.
AB - Emergency service organizations are "in combat" every day. Yet with the
experience and education we have amassed over the years, we remain ill-prepared
to deal with the full effects of a terrorist attack. Terrorism has many
definitions. For this article we choose this one: Terrorism: The use of violence,
threats, intimidation or information manipulation for revenge, politics, support
of a cause or the furthering of a criminal enterprise.
PMID- 10187434
TI - Geriatric assessment & specialized pathology. Practical advice for dealing with
an aging population.
PMID- 10187435
TI - 1999 buyer's guide.
PMID- 10187436
TI - Consultants can provide experience and expertise.
PMID- 10187437
TI - Worklist management: next stage for DICOM.
PMID- 10187438
TI - Biplane angio understates degree of carotid stenosis.
PMID- 10187439
TI - MR spectroscopy and SPECT capture chronic fatigue.
PMID- 10187440
TI - Spiral CT and the oncologic patient.
PMID- 10187441
TI - Arm ports provide long-term central venous access.
PMID- 10187442
TI - Optimize x-ray systems to minimize radiation dose.
PMID- 10187443
TI - Radiologists dither over use of nonionic contrast.
PMID- 10187444
TI - Experimental technology lurks at radiology's edge.
PMID- 10187445
TI - MRA volume grows as new applications emerge.
PMID- 10187446
TI - Studies split on value of thoracic overreads. Oncology review says yes, ER review
no.
PMID- 10187447
TI - Prenatal ultrasound evaluation now possible in first trimester. Nuchal
translucency thickness can spot Down's syndrome.
PMID- 10187448
TI - The education of a malpractice expert. Interview by John C. Hayes.
PMID- 10187449
TI - Survey reveals healthy growth in teleradiology.
PMID- 10187450
TI - Lower radiation exposure improves patient safety.
PMID- 10187451
TI - Charles R. Drew University cited for inner-city telemedicine.
PMID- 10187452
TI - Indonesia launches satellite.
PMID- 10187453
TI - When seconds count, online radiology services are a lifesaver.
PMID- 10187454
TI - Live transmissions show heartbeats around the world.
PMID- 10187455
TI - Telemedicine device encourages patients to take medications.
PMID- 10187457
TI - U.S. Navy centers participate in Baltic maneuvers.
PMID- 10187458
TI - AT&T Canada demonstrates ATM capabilities.
PMID- 10187456
TI - Siemens establishes India software center.
PMID- 10187459
TI - Virgin Atlantic provides medical services in the air.
PMID- 10187460
TI - Doctors walk in patients' footsteps via virtual reality technology.
PMID- 10187461
TI - Center for really neat research changes quality of life for handicapped patients.
PMID- 10187462
TI - Rural Health Care Corp. Makes two awards.
PMID- 10187463
TI - "Virtual Creatures" teach biology without dissection.
PMID- 10187464
TI - Urology operations linked to four sites.
PMID- 10187465
TI - Practice brief. Electronic signatures (updated). American Health Information
Management Association.
PMID- 10187466
TI - A different path to managing change.
PMID- 10187467
TI - HHS publishes notice of proposed rule making for security, electronic signature
standards.
PMID- 10187468
TI - The state of the computer-based patient record.
AB - Value, experiments, promises, disappointments, hype, compromises, and change all
characterize the status of the computer-based patient record (CPR). An industry
expert offers some perspective on where the CPR has been and where it's going.
PMID- 10187469
TI - Government moves ahead with CPR endeavor.
PMID- 10187470
TI - Implementing the enterprise master patient index.
AB - In implementing a cross-facility initiative, the importance of planning and
understanding the implications for all facilities can't be overlooked. Here's how
one integrated delivery network navigated the challenges of implementing a cross
facility enterprise master patient index.
PMID- 10187471
TI - CPR success stories.
AB - What kind of planning goes into implementing a computer-based patient record, and
how can HIM professionals participate in this process? Two practitioners who've
been there discuss how they were able to use their expertise in CPR projects--and
the results that followed.
PMID- 10187472
TI - Components of the CPR: an overview.
PMID- 10187473
TI - Continuous speech recognition: what you should know.
PMID- 10187474
TI - Legal medical record redefinition in a multimedia environment.
AB - As health information expands beyond the traditional paper-based medical record,
HIM professionals need to confront the issues related to defining the medical
record. The author provides a detailed assessment guide to the redefinition
process.
PMID- 10187475
TI - Performance improvement for documentation.
PMID- 10187476
TI - Getting the most out of HIM week.
PMID- 10187477
TI - FY1999 inpatient PPS changes; ICD-9-CM revisions.
PMID- 10187478
TI - Emerging technologies: has their time come?
PMID- 10187479
TI - Intensive care: the next level for IT.
AB - Intensive patient care areas like the emergency room, surgical suites and
intensive care units have their own challenges, radically different from other
inpatient units. Automating these areas requires a different level of IT product,
design and development.
PMID- 10187480
TI - Evaluating IT investments.
AB - Before you sign on the dotted line, you know where your money is going. But do
you understand the impact of IT investments and the scale and complexity of the
project--key elements of evaluating an IT proposal?
PMID- 10187481
TI - What works. $3M savings projected in TCO (total cost of ownership) review.
PMID- 10187482
TI - What works. Electronic repository saves $1 million plus.
PMID- 10187484
TI - HotList: EDI, electronic commerce.
PMID- 10187483
TI - What works. Dietary IVR (interactive voice recognition) nets a million in savings
for NY hospital.
PMID- 10187485
TI - Getting at the heart of the IT turnover puzzle.
PMID- 10187486
TI - With worries galore, should health care rely on the Internet?
AB - Some pioneering health care organizations are using the public Internet for more
than just basic Web sites. But will fears about the reliability and security of
the Internet keep most organizations from using the worldwide network of computer
networks? In this story, experts debate the issue.
PMID- 10187487
TI - Intranet strategies: how organizations' approaches are evolving.
PMID- 10187488
TI - Beyond billboards: building interactive Web sites.
AB - More organizations are developing interactive Web sites that go beyond simple
billboard-like advertising. These hospitals, integrated delivery systems,
physician group practices and managed care organizations are finding that
interactive Web sites are helping them improve service for a modest cost.
PMID- 10187489
TI - Winning over physicians.
PMID- 10187490
TI - A virtual private network strategy.
PMID- 10187491
TI - MedPartners' extranet survives.
PMID- 10187492
TI - The Web's role in an emergency.
PMID- 10187493
TI - 15 fund-raising opportunities with the millionaire next door.
PMID- 10187494
TI - A multiyear campaign success story: no magic, no secret, no ending.
PMID- 10187495
TI - Stalking the silent bequest: three myths about bequest donors.
PMID- 10187496
TI - On patience.
PMID- 10187497
TI - "A pile of money".
PMID- 10187498
TI - Sage advice for new fund raisers.
PMID- 10187499
TI - Joint working. Arranged marriages.
PMID- 10187500
TI - Joint working. Duel carriageway.
PMID- 10187501
TI - Homelessness. In from the cold.
AB - A multidisciplinary team formed in January to help rough sleepers in Leicester
has found accommodation for half the clients considered. The average age of
clients is 35, and three-quarters are male. The initiative has built on existing
joint working partnerships in Leicester.
PMID- 10187502
TI - Integrated care. Quebec on call.
PMID- 10187503
TI - On the evidence. Colorectal surgery.
PMID- 10187504
TI - Clinical decision making. The searchers.
PMID- 10187505
TI - Primary care. Net values.
PMID- 10187506
TI - Patient records. At GPs' fingertips.
PMID- 10187507
TI - Redundancy. In the firing line.
PMID- 10187508
TI - Redundancy. The wasteland.
PMID- 10187509
TI - Human resources. Opportunities knock.
PMID- 10187510
TI - Responding to the realities of an aging society.
PMID- 10187511
TI - One year later: the BBA (Balanced Budget Act) hits Catholic healthcare.
PMID- 10187512
TI - The False Claims Act: where it stands.
PMID- 10187513
TI - Three reasons to use CHAusa.
PMID- 10187514
TI - Still innovative after all these years. Bon Secours Health System has new
sponsorship structure. Interview by Gordon Burnside.
AB - In an interview with Health Progress, Sr. Patricia A. Eck, DBS, and Christopher M
Carney, respectively the chairperson of the board and president/chief executive
officer of Bon Secours Health System, Inc. (BSHSI), Marriotsville, MD, talked
about their system, the Catholic health ministry, and not-for-profit healthcare
in general. BSHSI is sponsored by the Congregation of Bon Secours, which was
founded in Paris in 1824 to provide home healthcare for the poor. After coming to
this country in 1881, the congregation continued giving home care and eventually
established several hospitals, primarily on the East Coast. BSHSI was established
in 1983 as a small network, but has since grown significantly, especially in the
1990s, as a number of formerly independent hospitals have chosen to join the
system. Today BSHSI comprises 14 acute care hospitals, 6 long-term care
facilities, 6 assisted-living facilities, and 10 home care organizations, in nine
communities.
PMID- 10187515
TI - Alienation and administration. System restructuring often entails four types of
canonical acts.
AB - When applying canon law to healthcare transactions, difficulties often arise in
determining whether the transaction or restructuring in question constitutes a
canonical act of alienation or an act of administration. Changes in system
governance may leave local property titles untouched, suggesting that no
alienation has taken place, but loss of Catholic identity or a reduced ability to
carry out the Church's mission may indeed constitute alienation. Often in
restructurings, four types of canonical acts are involved: alienation of property
(alienation in the strict sense), acts that can jeopardize the stable patrimony
(sometimes called alienation in the broad sense), acts of ordinary
administration, and acts of extraordinary administration. While alienation
concerns the divestiture of ownership, the general purpose of administration is
to preserve goods. Acts of extraordinary administration require certain
formalities of consent before they can be carried out. However, the intervention
of the Holy See is not required, as it is for acts of alienation. The permission
may be granted in principle, before a formal offer is received; after an offer is
received; or, in some cases, by a "blanket" indult. A restructuring can amount to
an alienation unless care is taken to verify to maintain certain reserved powers,
thus ensuring that the work is still under the direction or canonical control of
the sponsoring religious institute or diocese. Joint ventures, however, seldom
involve insoluble canonical problems. Each situation must be evaluated
individually and care taken to ensure that the requirements of both
eccleslastical and secular law are met.
PMID- 10187516
TI - Corporate compliance is not enough. Catholic healthcare organizations should aim
at the development of ethical cultures.
PMID- 10187517
TI - A new role for the Church. Dioceses should do more in providing care for
dependent and dying persons.
AB - In 1988, with the publication of Catholic Health Ministry: A New Vision for a New
Century, the Commission on Catholic Health Care Ministry called on the Church to
redefine its healing mission in society. Unfortunately, despite various efforts,
the Church has not yet fully articulated a shared vision of Catholic healthcare,
healing, and support. Healing human brokenness has always been the Church's work
in the world, whether the brokenness be physical, emotional, intellectual, moral,
or spiritual. The Church, having a broader definition of brokenness than that of
the larger healthcare system, must sometimes act as a countercultural critic of
that system. Two of the great challenges facing healthcare today are providing
care for dependent persons (people with chronic illnesses and older people) and
for dying persons. In both cases, much more coordination of the various actors is
needed. The Church could ensure that this coordination is carried out. In each
diocese, the bishop should organize a pastoral health and social service planning
group to assess community needs and apply Church resources to them. Local
Catholic healthcare providers and social service agencies should develop a
corporate culture of healing and support. Parishes should accept the idea that
healing and supporting frail people are integral parts of parish life.
PMID- 10187518
TI - Building true collaborations. A senior support network illustrates a successful
partnership of healthcare and social service providers.
AB - The relationship between Catholic Social Services (CSS) of the Diocese of
Scranton and Mercy Health Partners--Northeast Region, which joined forces last
year to develop a senior support network for residents of Wilkes-Barre and the
Borough of Kingston, PA, illustrates how collaboration grows out of cooperation
and coordination of services. The network is a project of the Neighborhood-Based
Senior Care National Initiative, which works to develop collaborations between
Catholic health systems and Catholic Charities agencies to help poor communities
meet the needs of aging persons. Barriers to successful collaboration may stem
from cultural misunderstandings, differences in organizational stability and
decision-making processes, attitudes toward money, and even professional
vocabularies. Organizations that trust and respect each other can overcome these
barriers. The Wilkes-Barre project began simply, but its success established a
pattern of cooperation between CSS and Mercy Health Partners, which led to
further coordination of referral programs, development of community health
profiles, and cross-organizational training. After nine months on the Wilkes
Barre project, CSS and Mercy Health Partners are now developing a Program of All
Inclusive Care for the Elderly (PACE). Effective collaboration between healthcare
providers and social service agencies is a long, sometimes difficult, process
that requires organizational commitments of time and resources. Organizations
must not yield to the temptation to take shortcuts to achieve short-term gains.
PMID- 10187519
TI - PACE (Program of All-Inclusive Care for the Elderly): innovative care for the
frail elderly. Comprehensive services enable most participants to remain at home.
AB - PACE--the Program of All Inclusive Care for the Elderly--provides integrated
comprehensive healthcare services to the frail elderly on a capitated basis.
Begun in the early 1970s in San Francisco's Chinatown, PACE today comprises many
individual programs across the nation. PACE's goal is to provide participants
with the healthcare services they need for the highest possible level of
functioning and autonomy. A typical PACE program is divided into sites, each of
which serves 120 to 150 participants. Most participants come several times a week
to the site's adult day care center, where they see members of an
interdisciplinary team that includes physicians, nurses, social workers,
therapists, and others. Home care is provided to participants unable to attend
the center. PACE is financed by capitated payments from Medicare and Medicaid,
which put providers at full risk for the services used by participants. The
flexibility provided by this funding enables PACE to offer a wide variety of
services, including supportive housing, which help keep participants out of
institutions. Estimates of Medicare savings attributed to PACE are 12 percent and
higher.
PMID- 10187520
TI - Long-term care alliances. Thriving in a managed care marketplace.
PMID- 10187521
TI - A better approach to care of the dying. Catholic healthcare and the Catholic
community can present an alternative to physician-assisted suicide.
AB - To combat physician-assisted suicide, Catholic healthcare and the Catholic
community cannot solely focus on mounting campaigns and formulating policies.
They must also demonstrate an alternative way to approach death and care of the
dying, taking a leadership role in improving end-of-life care. To accomplish
this, Catholic healthcare must foster a culture that recognizes death as the
inevitable outcome of human life and makes care for the dying as important as
care for those who may get well. The ministry must acknowledge the limits of
human life, human abilities, human ingenuity, and medical technology; and respect
decisions to forgo life-sustaining therapies. In addition, physicians must
address advance directives with patients before hospitalization and must be
willing to offer hospice care as an option to dying patients and their families.
More effective pain management must be devised. Catholic facilities must develop
palliative care policies and commit to ongoing education to provide such care. It
is essential that they pay attention to the environment in which patients die;
identify the physical, psychosocial, and spiritual needs of family members; and
use prayer and rituals in meaningful ways. With a clear focus on improving end-of
life care, Catholic healthcare--in partnership with other denominations--can
eliminate some of the factors that can make physician-assisted suicide seem
appealing to suffering people.
PMID- 10187522
TI - Leading with integrity. How to balance conflicting values.
AB - Reports of lapses in organizational integrity and ethical behavior are disturbing
and point to the need for leaders committed to organizational integrity. In
recent years, organizations have increased their attention to codes of compliance
and compliance programs, but these programs focus on minimal requirements and are
not a manifestation of integrity. Leaders must create integrity-based ethics
programs, which direct corporate actions and goals and assist in shaping
organizational relationships and decisions based on mission, vision, and core
values. Organizational leaders must hold values that may be in conflict in a
balanced tension. Such conflicting values include the Hippocratic tradition and
population-based healthcare, caring for patients and families and containing
costs, and competition and collaboration. Leaders can model integrity by
addressing conflicting values overtly in decision-making processes.
PMID- 10187523
TI - Community networks. Hospice of St. Francis Community Bereavement Council, New
Castle, PA.
PMID- 10187524
TI - Community networks. Hannah's House, Mishawaka, IN.
PMID- 10187525
TI - Mini-medical school showcases medical careers to school children.
PMID- 10187526
TI - Three trends put frail elderly in peril.
PMID- 10187527
TI - Joint Commission supports organ and tissue donation initiative.
PMID- 10187528
TI - Special report on cooperative agreements and government recognition and reliance.
Cooperative accreditation initiative grows.
PMID- 10187529
TI - Special report on cooperative agreements and government recognition and reliance.
States recognize Joint Commission accreditation.
PMID- 10187530
TI - Special report on cooperative agreements and government recognition and reliance.
Federal deemed status option for four types of accredited organizations.
PMID- 10187531
TI - Special report on cooperative agreements and government recognition and reliance.
Reciprocal recognition of Medicare-certified entities expanded under network
program.
PMID- 10187532
TI - Intent statements for Environment of Care standards for hospice care revised.
PMID- 10187533
TI - Joint Commission and U.S. Air Force move Project Odyssey into phase II.
PMID- 10187534
TI - CTs may get new role. Research backs widespread use in lung-cancer screening.
PMID- 10187535
TI - Showdown at PPS gap. OIG, hospitals at odds over outpatient formula's impact.
PMID- 10187536
TI - Hospital bags Medicare HMO deal.
PMID- 10187537
TI - Trying to beat the odds. Minn. providers to launch health plan despite
statistics.
PMID- 10187538
TI - AHERF-like symptoms. Struggling Detroit Medical Center works on turnaround.
PMID- 10187539
TI - Study ties staffing, complications.
PMID- 10187540
TI - No deal? Columbia-Alexian Brothers swap hits antitrust snag.
PMID- 10187541
TI - All benchmarked out. Even the top 100 hospitals can't find many more ways to be
more productive.
AB - The nation's best-performing hospitals, as determined by two healthcare
management and consulting firms, still register results that separate them from
the pack. The hospitals' successes are chronicled in 100 Top Hospitals:
Benchmarks for Success, an annual analysis that uses nine measures of clinical,
operational and financial performance to rate hospitals.
PMID- 10187542
TI - Market profile. San Diego market is steady as a rock. Not-for-profits, stability
dominate.
PMID- 10187544
TI - Variation on a theme. Columbia changes its tune about benefit of property taxes.
PMID- 10187543
TI - Second time isn't the charm. Doctor-run HMO in Maryland meets same fate as
original.
PMID- 10187545
TI - No excuses for dumping. HHS: Don't use managed-care coverage as rationale.
PMID- 10187546
TI - Helping workers stretch away strain.
PMID- 10187547
TI - The dark side of going private.
PMID- 10187548
TI - Defined contribution: it's inevitable.
PMID- 10187549
TI - The gender gap. Health care's next frontier.
PMID- 10187550
TI - Curbing the tobacco craving.
PMID- 10187551
TI - Patchwork protection ... patient rights.
PMID- 10187552
TI - Data watch. Last-minute absences cost big bucks.
PMID- 10187553
TI - Medicine goes Madison Avenue: an evaluation of the effect of direct-to-consumer
pharmaceutical advertising on the learned intermediary doctrine.
PMID- 10187554
TI - Solicitation of comments on the OIG/HCFA Special Advisory Bulletin on the patient
anti-dumping statute--OIG and HCFA. Notice of proposed special advisory bulletin.
AB - This Federal Register notice seeks the input and comments of interested parties
on a Special Advisory Bulletin being developed by the OIG and HCFA designed to
address requirements of the patient anti-dumping statute and the obligations of
hospitals to screen all patients seeking emergency services and provide
stabilizing medical treatment to enrollees of managed care plans if their
condition warrants it. In developing this proposed issuance and soliciting public
comment, it is our goal to provide clear and meaningful advice with regard to the
application of the anti-dumping provisions, and ensure greater public awareness
of the hospitals' obligations in providing emergency medical services to those
individuals insured by managed care plans.
PMID- 10187555
TI - Federal-state joint board on universal service--FCC. Proposed rule; recommended
decision.
AB - On November 24, 1998, the Federal-State Joint Board adopted a Second Recommended
Decision regarding universal service. In this decision, the Joint Board made
numerous recommendations on universal service issues. The Joint Board recommends
a federal high cost support mechanism for non-rural carriers that enables rates
to remain affordable; that the Commission replace the 25/75 jurisdictional
division of responsibility for high cost support; that the Commission compute
federal high cost support for non-rural carriers through a two-step process; and
that the mechanisms outlined be reviewed no later than three years from July 1,
1999. The Commission seeks comment on the Second Recommended Decision.
PMID- 10187556
TI - Medicare and Medicaid programs; quarterly listing of program issuances--second
quarter, 1998--HCFA. Notice.
AB - This notice lists HCFA manual instructions, substantive and interpretive
regulations, and other Federal Register notices that were published during April,
May, and June of 1998 that relate to the Medicare and Medicaid programs. It also
identifies certain devices with investigational device exemption numbers approved
by the Food and Drug Administration that may be potentially covered under
Medicare. Section 1871(c) of the Social Security Act requires that we publish a
list of Medicare issuances in the Federal Register at least every 3 months.
Although we are not mandated to do so by statute, for the sake of completeness of
the listing, we are including all Medicaid issuances and Medicare and Medicaid
substantive and interpretive regulations (proposed and final) published during
this timeframe.
PMID- 10187557
TI - Medicare program; criteria and standards for evaluating intermediary and carrier
performance: millennium compliance--HCFA. General notice with comment period.
AB - This notice revises the criteria and standards to be used for evaluating the
performance of fiscal intermediaries and carriers in the administration of the
Medicare program. This revision establishes a performance standard requiring
these contractors to meet requirements for millennium compliance. We require
contractors to certify that they have made all necessary system(s) changes and
have tested those systems in accordance with HCFA guidelines.
PMID- 10187558
TI - Investigational new drug applications; clinical holds--FDA. Direct final rule.
AB - The Food and Drug Administration (FDA) is amending its regulations governing
investigational new drug applications (IND's) for human drug and biological
products. This action amends the IND clinical hold requirements to state that the
agency will respond in writing to a sponsor's request that a clinical hold be
removed from an investigation within 30-calendar days of the agency's receipt of
the request and the sponsor's complete response to the issue(s) that led to the
clinical hold. FDA is taking this action in accordance with provisions of the
Food and Drug Administration Modernization Act of 1997 (the Modernization Act).
Elsewhere in this issue of the Federal Register, FDA is publishing a companion
proposed rule under FDA's usual procedure for notice-and-comment rulemaking to
provide a procedural framework to finalize the rule in the event the agency
receives significant adverse comments and withdraws this direct final rule.
PMID- 10187559
TI - Medicare and Medicaid program; civil money penalties, assessments, exclusions,
and related appeals procedures--HCFA. Final rule with comment period.
AB - This rule establishes procedures for imposing civil money penalties, assessments,
and exclusions for certain violations of the Medicare and Medicaid programs. The
regulations also provide for hearings and appeals when those penalties,
assessments, and exclusions are imposed. These procedures are based on the
procedures that the Office of the Inspector General has promulgated for the civil
money penalties, assessments, and exclusions. These regulations are designed to
protect program beneficiaries from unfit health care practitioners and to
otherwise improve antifraud provisions under the Medicare and Medicaid Acts.
PMID- 10187560
TI - Investigational new drug applications; clinical holds; companion document to
direct final rule--FDA. Proposed rule.
AB - The Food and Drug Administration (FDA) is proposing to amend its regulations
governing investigational new drug applications (IND's) for human drug and
biological products. This proposed action would amend the IND clinical hold
requirements to state that the agency will respond in writing to a sponsor's
request that a clinical hold be removed from an investigation within 30-calendar
days of the agency's receipt of the request and the sponsor's complete response
to the issue(s) that led to the clinical hold. This proposed action is being
taken in accordance with provisions of the Food and Drug Administration
Modernization Act of 1997 (the Modernization Act). This proposed rule is a
companion document to a direct final rule published elsewhere in this issue of
the Federal Register. If FDA receives any significant adverse comment, the direct
final rule will be withdrawn, and the comments will be considered in the
development of a final rule using usual notice-and-comment rulemaking based on
this proposed rule.
PMID- 10187561
TI - Left behind: the seriously mentally ill in the managed care era. Interview by
Robin Dorman.
PMID- 10187562
TI - Chasing a rainbow: integrated delivery. Systems find behavioral health one of the
toughest challenges.
PMID- 10187563
TI - Behavioral health helps AMCs (academic medical centers) stave off extinction.
PMID- 10187564
TI - Moving from hospital networks to integrated systems.
PMID- 10187565
TI - National survey results. Behavioral integrated systems come of age.
PMID- 10187566
TI - Managed care vs. provider networks. What's the better model? Discussion.
PMID- 10187567
TI - Description or prescription? Clinical decision-support tools in treatment
planning.
PMID- 10187568
TI - The roles of the behavioral health professional in integrated systems.
AB - It is surprising that integration has only recently re-emerged as a major issue
in healthcare. It has taken the economic pressures of managed care and the
demands from employers for accountability to place integration in the spotlight.
Without these pressures, we would most likely continue to focus our attention in
behavioral health on the preservation of traditional professional roles and
boundaries, instead of focusing on prevention and developing processes that
produce the best outcome for the patient at the lowest possible cost. Integration
challenges traditional roles and processes, forcing institutions in our field to
change. Role change, as sociologists know, can be profoundly disorienting to
individuals and is often vehemently resisted by groups and institutions who have
an investment in the status quo. That is where we are now in this field despite
our current enthusiasm for this rather innocent-looking concept called
integration. We should be confident that the innovators in healthcare will
succeed. The economy and quality-of-care concerns demand it. I hope they receive
something more than a lukewarm reception.
PMID- 10187569
TI - Catching the age wave: post-acute continuum of care.
PMID- 10187570
TI - Post-acute needs innovative financing models.
PMID- 10187571
TI - PPS reimbursement analysis: impact of the 1997 Balanced Budget Act upon post
acute rehabilitation services.
PMID- 10187572
TI - Future market trends for post-acute services.
PMID- 10187573
TI - CM credentials: it's quickly becoming a case of when, not if you must.
AB - Many case managers feel pressured by an increasingly competitive job market to
take advantage of the recent proliferation in case management credentials and
degree programs. And data suggest that credentialed and better-educated case
managers can bring home significantly higher salaries. Even so, some experts are
critical of the trend toward raising the educational requirements for some of the
top case management credentials. At issue is whether the bachelor of science in
nursing should be regarded as a minimum standard for the practice of case
management. Most experts agree, however, that having a credential indicates that
a case manager is attempting to broaden his or her base of knowledge and stay
current with trends in quality and patient care.
PMID- 10187574
TI - Certification programs target CM departments.
AB - Two organizations--the Commission on Accreditation for Rehabilitation Facilities
(CARF) and the American Accreditation HealthCare Commission/URAC--are developing
accreditation standards for case management departments. Both will be available
sometime next year. Just as certification has helped establish a benchmark for
individual practice, these organizations hope their programs will establish
larger-scale benchmarks for whole departments. It's expected that the CARF
standards will be geared more toward acute care, while the Commission/URAC will
apply more to payer-based programs.
PMID- 10187575
TI - Meet the new kids on the credentialing block.
AB - The Washington, DC-based American Nurses Credentialing Center's nurse case
manager credential continues to get a rocky reception. Following difficulties
with last year's test and controversy over the credential's eligibility criteria,
the number of applicants remains small. Meanwhile, the inaugural test for the
Center for Case Management's new case management administrator certified
credential took place on Oct. 24, 1998. While results are not yet available,
officials at the South Natick, MA-based Center report that the diversity of
candidates for the credential reflected the exam's cross-continuum focus. The
Oakbrook Terrace, IL-based Joint Commission on Accreditation of Healthcare
Organizations is still developing its upcoming "Diplomate of the Academy"
credential, which will feature a formal curriculum and course work.
PMID- 10187576
TI - HCM's annual directory of the top CM credentials.
PMID- 10187577
TI - Fast-tracking clinical pathway redesign. Part I: The redesign process.
PMID- 10187578
TI - Community therapy moves rehab out of the hospital.
PMID- 10187579
TI - Outcomes, practice pattern used to set benchmarks.
PMID- 10187580
TI - Menu-type day program is a hit with payers.
PMID- 10187581
TI - HCFA gives more information on PPS cost allocation; comment period may be
extended.
PMID- 10187582
TI - JCAHO disputes findings on private sector accreditation of nursing facilities.
PMID- 10187583
TI - Industry supports call for national criminal background check system.
PMID- 10187584
TI - Re-evaluation, renegotiation of vendor arrangements essential under PPS.
PMID- 10187585
TI - Stats & facts. Back to basics: MCO enrollment and choices.
PMID- 10187586
TI - Cataracts.
PMID- 10187587
TI - Creating a benefit management information database.
AB - In this case study, a real-life information technology conundrum is fictionalized
to illustrate the potential benefits of retaining corporate knowledge through the
creation of an information repository in a managed health care plan.
PMID- 10187588
TI - Providing health economic data to managed care.
PMID- 10187589
TI - The role of medication adherence.
PMID- 10187590
TI - Medication nonadherence: Part II--A pilot study in patients with congestive heart
failure.
AB - Nonadherence is a significant medical problem in the United States, leading to
excessive morbidity, mortality, and medical costs. In the conclusion to this two
part article, the authors describe a pilot study involving 311 patients taking an
angiotensin-converting enzyme inhibitor that evaluates the principal factors for
nonadherence to pharmaceutical therapy in patients with congestive heart failure.
PMID- 10187591
TI - Contract leveraging: a strategy for provider groups in managed care.
AB - Using one's leverage in health care negotiation does not mean intimidating,
threatening, or even demanding a certain percentage of the premium. Leveraging is
not a game of who wins and who loses; rather, it is a negotiation technique. The
authors explain how to best use the abilities and proficiencies of a provider
group to negotiate contracts with MCOs.
PMID- 10187592
TI - Private health care provision in developing countries: a preliminary analysis of
levels and composition.
AB - While the importance of the private sector in providing health services in
developing countries is now widely acknowledged, the paucity of data on numbers
and types of providers has prevented systematic cross-country comparisons. Using
available published and unpublished sources, we have assembled data on the number
of public and private health care providers for approximately 40 countries. This
paper presents some results of the analysis of this database, looking
particularly at the determinants of the size and structure of the private health
sector. We consider two different types of dependent variable: the absolute
number of private providers (measured here as physicians and hospital beds), and
the public-private composition of provision. We examine the relationship between
these variables and income and other socioeconomic characteristics, at the
national level. We find that while income level is related to the absolute size
of the private sector, the public-private mix does not seem to be related to
income. After controlling for income, certain socioeconomic characteristics, such
as education, population density, and health status are associated with the size
of the private sector, though no causal relationship is posited. Further analysis
will require more complete data about the size of the private sector, including
the extent of dual practice by government-employed physicians. A richer story of
the determinants of private sector growth would incorporate more information
about the institutional structure of health systems, including provider payment
mechanisms, the level and quality of public services, the regulatory structure,
and labour and capital market characteristics. Finally, a normative analysis of
the size and growth of the private sector will require a better understanding of
its impact on key social welfare outcomes.
PMID- 10187593
TI - The progress of the Polio Eradication Initiative: what prospects for eradicating
measles?
AB - Although various attempts have been made to eradicate infectious diseases, only
smallpox has been eradicated to date. Polio is targeted for eradication in 2000
and already planning has begun for the eradication of measles. However, before we
commit to a measles eradication effort, we must examine the lessons to be learned
from polio eradication. Of particular importance is the debate over whether
resources should be invested in 'horizontal' or 'vertical' programmes. The
outcome of these debates will have a very deep and lasting impact on global
health development in years to come. Collaboration between targeted programmes
and the primary health care sector through polio and measles eradication efforts
will help bring about the necessary balance between goal-oriented programmes,
which are subject to quality control and can be evaluated by measurable outcomes,
and broader efforts to build up sustainable health infrastructure.
PMID- 10187594
TI - Researching the public/private mix in health care in a Thai urban area:
methodological approaches.
AB - The private health sector has been growing rapidly in many low and middle income
countries, yet not enough is known about its sources of finance or
characteristics of its users. Moreover, health care reform measures are leading
to alterations in the mix of public and private finance and provision, increasing
further the need for information. This paper presents and evaluates some research
methods which can be used to collect information relevant to considering policies
on the public/private mix. They comprise a household survey, a health diary and
interview survey, a bed census, and a health resource survey. Each method is
described as it was used in a study in a large urban setting in Thailand, and
strengths and weaknesses of the methods are identified. The use of data to
estimate the shares of public and private finance and provision, and particularly
private sources of finance of public hospitals and public sources of finance for
private hospitals, is demonstrated. Policy issues highlighted by the data are
identified.
PMID- 10187595
TI - The cost-effectiveness of forty health interventions in Guinea.
AB - Addressing diseases of a high burden with the most cost-effective interventions
could do much to reduce disease in the population. We conducted a cost
effectiveness analysis of 40 health interventions in Guinea, a low-income country
in sub-Saharan Africa, using local data. Interventions were selected from
treatment protocols at health centres, first referral hospitals and national
programmes in Guinea, based upon consultation with health care providers and
government plans. For each intervention, we calculated the costs (comprising
labour, drugs, supplies, equipment, and overhead) in relation to years of life
saved, discounted at 3%. The results show that the per capita costs and
effectiveness of any intervention vary considerably. Average costs show no clear
pattern by level of care, but effectiveness is generally highest for curative
hospital interventions. Several interventions have a cost-effectiveness of US$100
per year of life saved (LYS) or less, and address more than 5% of total years of
life lost. These include health centre interventions such as: treatment of
childhood pneumonia ($3/LYS); rehydration therapy for diarrhoea ($7/LYS);
integrated management of childhood pneumonia, malaria and diarrhoea ($8/LYS);
short-course treatment of tuberculosis ($12/LYS); treatment of childhood malaria
($13/LYS), and childhood vaccination ($25/LYS). Outreach programmes for
impregnated bed nets against malaria cost $43/LYS. Maternal and perinatal
diseases, have slightly less cost-effective interventions: integrated family
planning, prenatal and delivery care at health centres ($109/LYS) or outreach
programmes to provide prenatal and delivery care ($283/LYS). A minimum package of
health services would cost approximately $13 per capita, and would address a
large proportion (69%) of major causes of premature mortality. This minimum
package would cost about three times the current public spending on health,
suggesting that health spending needs to rise to achieve good health outcomes.
PMID- 10187596
TI - Enhancing health programme efficiency: a Cambodian case study.
AB - In 1995, the Cambodian Urban Health Care Association (CUHCA) was set up as
facilitator between private health care providers and patients, guaranteeing good
quality health care and fair pricing to patients and providing training and
logistic support to providers. Providers were engaged on a fee-for-service basis
and competition encouraged. CUHCA's objectives followed the same line of thought
as the 1993 World Development Report, aiming at influencing the unregulated
private health care market through competition mechanisms. But soon after the
start of the project the basic problem was recognized to be not the absence of
effective government regulation but rather that consumers lack the requisite
knowledge to make good choices in the market for health services. CUHCA had not
adequately addressed the demand for health services. The original supply-side
strategy of improving health services by increasing competition was a failure. In
order to improve CUHCA's health programme efficiency the association's objectives
were subsequently redefined and its functioning reorganized. CUHCA now tries to
educate consumers and provides good quality services so that consumers will be
able to act on the basis of their newly acquired knowledge. CUHCA's health
centres serve as model clinics for first-line health care. Community educators
organize information, education and communication (IEC) activities. Staff help
school teachers to improve formal health education in schools and CUHCA assists
local leaders in sanitation development. Only full-time personnel are employed,
encouraging team spirit and communication with the target population. Salaries
are based on team performance. The CUHCA programme demonstrates that, depending
on the market situation, health programme models need to address both the supply
and the demand for services in order to be efficient. Where consumers lack
essential knowledge to make appropriate choices in the health service market,
interventions should focus on health education and social marketing and provide
models of quality care catering to informed consumer choice.
PMID- 10187597
TI - Protecting paradise: tourism and AIDS in the Dominican Republic.
AB - This study summarizes results from six data collection instruments administered
to tourists, hotel workers, and commercial sex workers (CSWs) in the Dominican
Republic (D.R.). The objective of this study was to assess: 1. how HIV/AIDS may
affect tourism; 2. how tourists are likely to react to prevention campaigns; and
3. how tourism may affect the spread of HIV/AIDS. It was found that an
overwhelming proportion of tourists did not consider the prevalence of HIV to be
a factor when making their travel plans, and that most did not consider
themselves at greater risk of becoming infected while on holiday than when they
were at home. This study determined that the spread of HIV/AIDS was unlikely to
affect the demand for tourism services in the D.R. The study also found that most
tourists would respond positively to an HIV/AIDS prevention campaign and would
not be discouraged from visiting the D.R. because of such campaigns. Those most
receptive to prevention efforts were also those who felt they were at highest
risk, according to study data. Finally, it was determined that while most
tourists probably do not engage in high risk activities, there were some male and
female tourists who do engage in sexual encounters with multiple Dominican CSWs
and hotel employees. These encounters represent a risk to the health and economic
development of the D.R., as well as to tourists and their other sexual partners.
Based on these findings, it is recommended that in order to minimize the
potential social and economic impact of HIV/AIDS in the D.R., prevention messages
need to reach a number of groups which have not yet been adequately targeted.
These groups include tourists, with a special emphasis on 'sex tourists', and
hotel employees, with a special emphasis on entertainment staff.
PMID- 10187598
TI - Sustainability of health care: a framework for analysis.
AB - This paper introduces a conceptual framework which can be used to study the
sustainability of health services in developing countries. A health service is
considered sustainable when operated by an organizational system with the long
term ability to mobilize and allocate sufficient resources for activities that
meet individual or public health needs. The framework includes three clusters:
(1) contextual factors, which outline the task and general environment of the
services; (2) an activity profile, which describes the services delivered and the
activities carried out to deliver them; and (3) organizational capacity, which
shows the carrying ability (capability) of the organization in broad terms. In
this framework, health care provision is seen as an open system model where five
main factors determine how inputs are converted to outputs, linking them through
feedback loops. These factors are aims, technology, structure, culture and
process. The framework has proven useful in analyzing factors critical to
sustainability, and in describing structures and processes both in basic public
services and in private not-for-profit services. It should also be tested on more
complex systems, such as national health care.
PMID- 10187599
TI - Public hospital resource allocations in El Salvador: accounting for the case mix
of patients.
AB - National hospitals in developing countries command a disproportionate share of
medical care budgets, justified on the grounds that they have a more difficult
patient case mix and higher occupancy rates than decentralized district hospitals
or clinics. This paper empirically tests the hypothesis by developing direct
measures of the severity of patient illness, hospital case-mix and a resource
intensity index for each of El Salvador's public hospitals. Based on an analysis
of inpatient care staffing requirements, national hospitals are found to receive
funding far in excess of what case-mix and case-load considerations would
warrant. The findings suggest that significant system-wide efficiency gains can
be realized by allocating hospital budgets on the bases of performance-related
criteria which incorporate the case-mix approach developed here.
PMID- 10187600
TI - Determinants of patient choice of medical provider: a case study in rural China.
AB - This study examines the factors that influence patient choice of medical provider
in the three-tier health care system in rural China: village health posts,
township health centres, and county (and higher level) hospitals. The model is
estimated using a multinomial logit approach applied to a sample of 1877 cases of
outpatient treatment from a household survey in Shunyi county of Beijing in 1993.
This represents the first effort to identify and quantify the impact of
individual factors on patient choice of provider in China. The results show that
relative to self-pay patients, Government and Labour Health Insurance
beneficiaries are more likely to use county hospitals, while patients covered by
the rural Cooperative Medical System (CMS) are more likely to use village-level
facilities. In addition, high-income patients are more likely to visit county
hospitals than low-income patients. The results also reveal that disease patterns
have a significant impact on patient choice of provider, implying that the
ongoing process of health transition will lead people to use the higher quality
services offered at the county hospitals. We discuss the implications of the
results for organizing health care finance and delivery in rural China to achieve
efficiency and equity.
PMID- 10187601
TI - The quality of private and public primary health care management of children with
diarrhoea and acute respiratory infections in Tlaxcala, Mexico.
AB - In Tlaxcala, Mexico, 80% of the children who died from diarrhoea or acute
respiratory infections (ARI) in 1992-1993 received medical care; in more than 70%
of cases it was provided by a private general practitioner (GP). The present
study evaluated the quality of case management by private and public GPs to
children under five years of age with diarrhoea and ARI. During the clinical
observation, the treatment and counselling given to the mother were assessed with
the WHO guidelines as reference standard. A total of 41 private and 40 public GPs
were evaluated for the management of diarrhoea, and 59 private and 40 public GPs
for the management of ARI. For diarrhoea, half of the private GPs gave inadequate
rehydration therapy, 63% gave incorrect advice on diet, 66% and 49% made an
incorrect correct decision in the prescription of antimicrobial and symptomatic
drugs, respectively. Public GPs generally performed better in diarrhoea
management: 7% gave inadequate rehydration therapy, 13% gave wrong advice on
diet, 3% made a wrong decision in the prescription of symptomatic drugs and 28%
gave a wrong decision in antimicrobial prescription. In the management of ARI,
66% and 58% of private GPs made a wrong decision in the prescription of
antimicrobial and symptomatic drugs, respectively, compared to 30% and 20% of
public GPs, respectively. Counselling to the mother given by both private and
public GPs was considered inadequate in most cases of diarrhoea and ARI. These
results clearly show that private doctors, as important providers of medical
care, need to be included in the strategies to improve the quality of care of
children with diarrhoea and ARI. Future research needs to address the
determinants of the clinical practice of private doctors in countries like
Mexico.
PMID- 10187602
TI - How and why public sector doctors engage in private practice in Portuguese
speaking African countries.
AB - OBJECTIVE: To explore the type of private practice supplementary income
generating activities of public sector doctors in the Portuguese-speaking African
countries, and also to discover the motivations and the reasons why doctors have
not made a complete move out of public service. DESIGN: Cross-sectional
qualitative survey. SUBJECTS: In 1996, 28 Angolan doctors, 26 from Guinea-Bissau,
11 from Mozambique and three from S Tome and Principe answered a self
administered questionnaire. RESULTS: All doctors, except one unemployed, were
government employees. Forty-three of the 68 doctors that answered the
questionnaire reported an income-generating activity other than the one reported
as principal. Of all the activities mentioned, the ones of major economic
importance were: public sector medical care, private medical care, commercial
activities, agricultural activities and university teaching. The two outstanding
reasons why they engage in their various side-activities are 'to meet the cost of
living' and 'to support the extended family'. Public sector salaries are
supplemented by private practice. Interviewees estimated the time a family could
survive on their public sector salary at seven days (median value). The public
sector salary still provides most of the interviewees income (median 55%) for the
rural doctors, but has become marginal for those in the urban areas (median 10%).
For the latter, private practice has become of paramount importance (median 65%).
For 26 respondents, the median equivalent of one month's public sector salary
could be generated by seven hours of private practice. Nevertheless, being a
civil servant was important in terms of job security, and credibility as a
doctor. The social contacts and public service gave access to power centres and
resources, through which other coping strategies could be developed. The
expectations regarding the professional future and regarding the health systems
future were related mostly to health personnel issues. CONCLUSION: The variable
response rate per question reflects some resistance to discuss some of the
issues, particularly those related to income. Nevertheless, these studies may
provide an indication of what is happening in professional medical circles in
response to the inability of the public sector to sustain a credible system of
health care delivery. There can be no doubt that for these doctors the notion of
a doctor as a full-time civil-servant is a thing of the past. Switching between
public and private is now a fact of life.
PMID- 10187603
TI - Searching bibliographic databases effectively.
AB - The ability to search bibliographic databases effectively is now an essential
skill for anyone undertaking research in health. This article discusses the way
in which databases are constructed and some of the important steps in planning
and carrying out a search. Consideration is given to some of the advantages and
limitations of searching using both thesaurus and natural language (textword)
terms. A selected list of databases in health and medicine is included.
PMID- 10187604
TI - Evaluating your risk for Medicare billing fraud.
PMID- 10187605
TI - Questioning the integrated vision.
AB - Years of efforts to vertically integrate the nation's health care system hasn't
yielded much in the way of lower costs, reduced utilization and increased
revenues. Now, the organization that predicted a nation of fully integrated
health care systems identifies five market phenomena that characterize an
industry in migration and ten predictions of what will happen in the future.
PMID- 10187606
TI - Hospital intensive care units have to face the market realities of managed care.
AB - The ICU is one of the last hospital bastions to face the market realities of
managed care. Ellen Beck examines the situation and outlines what some hospitals
and health systems are doing to improve outcomes, administrative issues and the
experiences of patients and their families.
PMID- 10187607
TI - A neighborly way to reduce Medicaid costs.
AB - One of the keys to controlling the costs of Medicaid managed care patients is to
treat them before they become ill. Richard Frye, Ph.D., profiles the Community
Health Worker Outreach Program in Baltimore, which trains residents of
neighborhoods with high numbers of Medicaid beneficiaries how to teach their
chronically ill neighbors about improving their health.
PMID- 10187608
TI - Kleinke's "Bleeding Edge" sees utility role for providers.
AB - Hospitals will evolve into units of health care delivery systems that will
eventually resemble utilities, like water and the telephone, according to a new
book. Donald E.L. Johnson reviews Bleeding Edge: The Business View of Health Care
in the New Century, by J.D. Kleinke, and discusses the strategic implications of
Kleinke's predictions.
PMID- 10187609
TI - Data trends. Key organizational performance indicators.
PMID- 10187610
TI - At a glance. Medicare HMO penetration for selected states.
PMID- 10187611
TI - Questing for quality: QISMC-ly (quality improvement system for managed care)
cutting the QAPI.
PMID- 10187612
TI - The director of medical informatics: a new physician leader for IT initiatives.
AB - Integrated delivery systems (IDSs) recently have invested substantial financial
resources in information technology (IT) initiatives. But the return on that
investment for many IDSs in terms of improved productivity and reduced costs has
been less than anticipated. Therefore, to improve or enhance the success of IT
initiatives, some IDSs have sought to encourage more physician support of such
efforts by creating a new executive position--director of medical informatics-
designed to be filled by physician leaders who have knowledge and skill in
managing information systems. The director of medical informatics, who typically
reports to the CEO or CIO, coordinates IT initiatives that address physician
concerns and promotes physician buy-in.
PMID- 10187613
TI - IDS conversions to for-profit status: structuring the deal.
AB - Not-for-profit integrated delivery systems (IDSs) may convert assets to for
profit status in a variety of ways, but typically choose from three basic
conversion structures: sale of assets, joint ventures, and lease or management
agreements. To select the optimal conversion structure, not-for-profit IDS
executives should understand the forces driving their organization's desire or
need to effect such a conversion and examine the legal, business, and political
implications of each option in light of the organization's particular
circumstances.
PMID- 10187614
TI - Physician resource profiling enhances utilization management.
AB - Physician resource profiling, the analysis of a physician's resource consumption,
enhances performance uniformity and efficiency and assists in utilization
management. Developing reliable profiles requires the shared participation of an
organization's finance personnel and physicians. Selecting or developing
benchmarks for performance comparisons, assessing the integrity of the
organizational data used, and testing the developed profiles all should be
completed before the physician resource profiling can be used to support decision
making.
PMID- 10187615
TI - Managing utilization successfully in 12 not-so-easy steps.
AB - Managing utilization involves managing the processes of care, which requires a
system approach that coordinates services, eliminates redundancy in care
delivery, and makes use of alternatives to traditional methods of meeting
healthcare needs. On the caregiving level, internally developed benchmarks
illuminate efficient or unneeded practice patterns, hospitalist programs help
contain inpatient costs, and standard protocols and disease state management help
to maintain expected measurable outcomes. Wisely managing patient access to care,
relying upon case managers to oversee catastrophic care, assessing high-risk
senior citizens and promoting their and other patients' relationships with social
service agencies, and implementing patient education and prevention programs all
can be coordinated within the managed care system.
PMID- 10187616
TI - A successful PPMC (physician practice management company) acquisition strategy:
vision, focus and discipline.
AB - Acquisitions have become increasingly necessary for managed care organizations to
create product value and operating synergies. Physician practice management
companies (PPMCs) that have successfully acquired and consolidated group
practices and IPAs have a clear vision of their mission, focus on their target
markets, and adhere to a disciplined methodology of financial evaluation,
negotiation, and transition. Growing a PPMC entails risks, but expectations are
for continued expansion of these organizations. The vision-focus-discipline
method can help buyers adhere to a successful strategy during the acquisition
process.
PMID- 10187617
TI - Do healthcare managers have an ethical duty to admit mistakes?
AB - Historically, healthcare organizations have been reluctant to admit mistakes
because of potential legal liability. Admitting mistakes and taking corrective
and compensatory action may reduce the likelihood of a lawsuit and, if a lawsuit
is lost, may reduce the punitive damage award. Financial consequences involve
admitting mistakes and incurring the associated compensatory costs or not
admitting mistakes and incurring associated compensatory and punitive damages for
the mistakes that are discovered later. Ethical consequences revolve around
managers' duty to patients, the healthcare organization, and themselves and their
families.
PMID- 10187618
TI - Information technologies need to protect patient confidentiality.
AB - To meet the needs of an increasing number of persons who require access to
patient information, health systems have devoted significant financial resources
to developing computerized medical records. As these enterprisewide information
systems go online, however the risk of compromising patient confidentiality
increases dramatically. State laws regarding patient confidentiality vary
considerably, and national standards have not yet been established. Therefore,
health systems need to take steps to ensure that their computerized patient
records remain secure and confidential to avoid being found in violation of
patients' legal right to privacy.
PMID- 10187619
TI - Dynamic healthcare environment demands new career-planning tools.
AB - In 1997, HFMA launched an initiative designed to help members excel in their
careers. A primary goal of that initiative was the development of a professional
growth model incorporating the key skills, knowledge, and behaviors that
contribute to successful performance. This model, in turn, would be used as the
basis for the development of assessment tools to assist members in evaluating
both their strengths and areas in which growth is needed to further their
careers. While work on the assessment tools is still under way, the model itself
can serve as a valuable signpost for healthcare financial professionals reviewing
their career paths.
PMID- 10187620
TI - Physician network audits can improve financial performance.
AB - A physician network audit is one way to evaluate the strengths and weaknesses of
a network's performance in five key areas: practice operations, financial
management, strategy and vision, managed care readiness, and organizational
governance. An objective, comprehensive audit can help identify real versus
perceived problems that are troubling a network. Then steps can be taken to align
incentives and improve operating results.
PMID- 10187621
TI - Achieving business growth through minority equity partnerships.
AB - Healthcare organizations can become more accessible to patients and managed care
organizations and can expand their patient base by forming minority equity
partnerships with physician practices. By investing in practices, healthcare
organizations provide capital and guidance to help the practices grow. Such an
arrangement fosters goodwill as the physicians retain ownership interests, which
preserves their entrepreneurial spirit.
PMID- 10187622
TI - Implementing the electronic claims standard.
PMID- 10187623
TI - HCFA's uncertain year 2000 status.
PMID- 10187624
TI - Turning the revenue cycle upside-down.
PMID- 10187625
TI - At a glance. Out-of-pocket expenses as a percentage of private health expenses,
1991 versus 1996.
PMID- 10187626
TI - The bottom line: healthcare purchasers don't buy quality.
PMID- 10187627
TI - Medical intranets: architecture over applications.
PMID- 10187628
TI - Applying risk management strategies to strengthen an IDS's investment policy.
AB - The increased financial risk that not-for-profit integrated delivery systems have
assumed to function under managed care has required them to become increasingly
reliant on income and gains from their investment portfolios. This reliance
underscores the need for these organizations to take steps to effectively manage
their investment risk. Not-for-profit IDSs should establish a systematic approach
to investment risk management that is based on maintaining a sound fiduciary
infrastructure and having a clear understanding of risk exposures, the most
important of which are policy and market risk. Applying reasonable and common
sense risk management strategies to investment policy will enhance an IDS's
overall financial and competitive strength.
PMID- 10187629
TI - A quantitative rationale for investing in healthcare facilities.
AB - When considering investing in its facilities, a healthcare organization should
determine its competitive position by quantifying factors such as average age of
plant, inpatient days, occupancy rates, and inpatient versus outpatient revenue.
Average age of plant in years (AAP) can be compared with inpatient days per 1,000
population to determine an organization's AAP relative to the market and thus
whether investment is warranted. Occupancy rates per facility can be compared to
the total of all unoccupied beds in an organization to determine if some
facilities should be consolidated or closed. Understanding the relationship
between revenue trends and the number of projects undertaken to address shifts in
inpatient and outpatient volumes can help providers create the optimal
environment for patient care delivery.
PMID- 10187630
TI - Creative payment strategy helps ensure a future for teaching hospitals.
AB - The Colorado Medicaid Program in years past relied on disproportionate share
hospital (DSH) payment programs to increase access to hospital care for Colorado
citizens, ensure the future financial viability of key safety-net hospitals, and
partially offset the state's cost of funding the Medicaid program. The options to
finance Medicaid care using DSH payments, however, recently have been severely
limited by legislative and regulatory changes. Between 1991 and 1997, a creative
Medicaid refinancing strategy called the major teaching hospital (MTH) payment
program enabled $131 million in net payments to be distributed to the two major
teaching hospitals in Colorado to provide enhanced funding related to their
teaching programs and to address the ever-expanding healthcare needs of their low
income patients. This new Medicaid payment mechanism brought the state $69.5
million in Federal funding that otherwise would not have been received.
PMID- 10187631
TI - Developing physician pay arrangements: the cash and care equation.
AB - Developing physician compensation packages that help a healthcare organization
meet its business objectives while satisfying physician pay expectations requires
new ways of linking pay to physician performance. Such compensation arrangements
specifically should include pay tied to defined performance standards,
compensation linked to group performance, performance incentives based on
realistic, achievable goals, work performance measured by common criteria, and
similar pay ensured for similar work. Final pay arrangements also should include
items that are sometimes overlooked, such as fully delineated job
responsibilities, performance measures aligned correctly with performance areas,
and the value of benefits considered in the cash compensation levels.
PMID- 10187632
TI - Mining hidden value through strategic real estate plans.
AB - Healthcare providers can get the most from their real estate investments if they
manage them strategically rather than view them as a cost of doing business.
Organizations that develop strategic real estate plans can optimize the cost
effectiveness of their assets, reduce operating costs, and create cash through
disposition strategies. The cost-effectiveness of assets can be optimized by
using off-balance-sheet financing structures, such as outright sale, sale-lease
back arrangements, synthetic leases, and beneficial occupancy agreements.
Opportunities for cost reduction can be found by conducting operations,
administrative, and maintenance reviews and cost-segregation studies. Cost
reduction efforts also should focus on ensuring space is used in the most
productive manner possible and that the organization pays no more than the
minimum required property tax. Disposition strategies should begin with
inventorying real estate assets to identify surplus assets. Such assets then can
be moved off the balance sheet or converted into commercial or public uses.
PMID- 10187633
TI - Hospital-affiliated practices: still looking for financial daylight.
PMID- 10187634
TI - Easing the transition to an RBRVS-based physician compensation system.
AB - In many provider organizations, traditional physician compensation systems based
on patient charges have been replaced with resource-based relative value scale
(RBRVS) systems, which pay physicians for actual effort expended. Group practices
considering adopting an RBRVS-based system should be aware that the transition
from one system to another requires careful planning. A four-step process that
can ease this transition includes organizing a transition team, comparing CPT
codes with the relative-value unit (RVU) schedule, designing and developing an
RVU-based report, and analyzing RVU production data.
PMID- 10187635
TI - Hospital transfers and discharges redefined.
PMID- 10187637
TI - Data trends. Is hospital profitability up or down?
PMID- 10187636
TI - Financing growth through cash-flow and asset-value credit facilities.
PMID- 10187638
TI - Guide to gall bladder surgery. Cut above the others.
PMID- 10187639
TI - Respiratory disease. Congestion at British airways.
PMID- 10187640
TI - Prostate cancer. It couldn't happen here.
PMID- 10187641
TI - Obesity. Lifting the burden.
PMID- 10187642
TI - We'll take the high road.
PMID- 10187643
TI - Devolution. Separate ways.
AB - Devolution will bring health policy under the democratic control of the directly
elected Scottish parliament and Welsh assembly. Some fear that members of these
bodies may wish to interfere in service delivery, rather than concentrating on
strategy. Devolution could highlight anomalies in health spending. Many
professionals fear that devolution will fragment UK-wide policy networks.
PMID- 10187644
TI - Primary care. Time bomb.
PMID- 10187645
TI - Public health. Evening all.
AB - The NHS's most significant contribution to reducing inequalities will be through
partnerships with other organisations. Many health authorities have set targets
and these vary greatly. HAs need to consider how susceptible any target is to
local action.
PMID- 10187646
TI - Integrated care. Emergency ward zen.
AB - Integrated working between primary and secondary care has enabled one acute and
community trust to reduce its emergency admissions by 8 per cent over three
years. This has enabled the closure of 18 medical beds in this year's contracting
round, with savings of over 400,000 Pounds. GPs and consultants have undertaken a
process of peer review to identify doctors with high admission rates or
inappropriate use of admissions.
PMID- 10187647
TI - Medical staffing. Quick march.
PMID- 10187648
TI - Medical staffing. Duty calls.
PMID- 10187649
TI - Medical staffing. Asian few.
PMID- 10187650
TI - Medical staffing. Bend it.
PMID- 10187651
TI - Deliberate self-harm.
PMID- 10187652
TI - Health policy issues and applications for evidence-based medicine and clinical
practice guidelines.
AB - Evidence-based medicine and clinical practice guidelines have become increasingly
salient to the international health care community in the 1990s. Key issues in
health policy in this period can be categorised as costs and access to care,
quality of and satisfaction with care, accountability for value in health care,
and public health and education. This paper presents a brief overview of evidence
based medicine and clinical practice guidelines and describes how they are likely
to influence health policy. Evidence-based medicine focuses on the use of the
best available clinical (efficacy) evidence to inform decisions about patient
care; guidelines are statements systematically developed from efficacy and
effectiveness research and clinical consensus for practitioners and patients to
use in making decisions about appropriate care under different clinical
circumstances. Both fields have developed methods for evaluating and synthesising
available evidence about the outcomes of alternative health care interventions.
They have clear implications for health policy analysts: greater reliance should
be placed on scientific evidence, policy decisions should be derived
systematically, and health care decisionmaking must allow for the active
participation of health care providers, policy makers, and patients or their
advocates. The methods and information generated from evidence-based guidelines
efforts are critical inputs into health policy analysis and decision-making.
PMID- 10187653
TI - The new pharmaceutical policy in Italy.
AB - Pressed by an impressive series of corruption scandals and by a change of
attitude towards cost-containment, the Italian pharmaceutical sector's regulatory
environment was radically changed in 1994. Regulatory power was concentrated on a
national technical body (CUF) and a new set of measures was taken, including a
nationwide drug expenditure budget, a redefinition of both the positive list and
the cost-sharing rules, and new price-setting models. As a result, in the period
1993-1996, nominal expenditures decreased by about L 1600 billion (ECU 83.6
billion at 1997 exchange rate), that is from 13.3% to 11.0% of current National
Health Service (NHS) expenditure. While in the 1980s Italy was one of the most
generous countries in funding pharmaceuticals, it is now one of the most
parsimonious. Although the overall pharmaceutical market shrank in 1994 and 1995,
a substantial part of NHS drug-bill savings resulted from cost-shifting from the
public sector to patients, mainly because physicians have not aligned their
prescribing behaviour to the new positive list. The new Italian approach to
containing pharmaceutical costs has been certainly effective, at least in the
short run. However, new relevant issues are emerging regarding the fall of NHS
pharmaceutical coverage, the centralised nature of the Italian pharmaceutical
policy and the gap between scientific based policies and actual prescribing
behaviours.
PMID- 10187654
TI - Neonatal mortality in the Czech Republic during the transition.
AB - OBJECTIVES: To identify factors underlying the reduction in neonatal mortality in
the Czech Republic during the 1990s and to identify scope for further
improvements. DESIGN: Examination of trends in birth weight and birth weight
specific neonatal mortality in the Czech Republic and comparison with figures
from Sweden, which has one of the lowest neonatal mortality rates in Europe.
SETTING: The Czech Republic. SUBJECTS: All singleton births occurring in the
Czech Republic in 1989-1991 and 1994-1995, with a comparison group of all
singleton births in Sweden in 1989-1991. MAIN OUTCOME MEASURES: Neonatal
mortality rate. RESULTS: Despite a slight worsening in the birth weight
distribution, the neonatal mortality rate in the Czech Republic fell from 5.6 to
3.8 per thousand live births. This was due to an improvement in the survival of
infants at all birth weights but especially amongst the lightest. Eighty percent
of the overall improvement was due to greater survival among those under 2500 g.
Comparison with Swedish birth weight specific rates indicates that, for the
country as a whole, only small additional gains are likely as a result of
improved survival at a given birth weight but, instead, a reduction in the
proportion of low birth weight babies would have a much greater effect. Regional
analysis indicates that the improvements have been much greater in Prague than in
the rest of the country. CONCLUSIONS: An effective strategy to reduce neonatal
mortality in the Czech Republic should have two elements. The first is to address
the socio-economic determinants of low birth weight. The second is to reduce
regional inequalities in the quality of neonatal care. This should, however, be
supplemented by more detailed investigation to identify specific amenable
factors.
PMID- 10187655
TI - The role of outputs and outcomes in purchaser accountability: reflecting on New
Zealand experiences.
AB - Recent reforms in a number of countries' health systems have led to the
separation of funder, purchaser and provider roles and the strengthening of
funders' and purchasers' positions relative to providers. One of the aims of such
reforms is to improve accountability. This paper reports on experiences in New
Zealand where, in addition to improving the accountability of providers,
purchaser accountability has also been a key policy issue. Attempts have been
made in New Zealand to develop a funder-purchaser accountability framework based
on a mix of outcomes, outputs and inputs. This paper discusses the roles that
each might play in contracts and accountability relationships between funders and
purchasers. The paper concludes that holding purchasers accountable for outcomes
is likely to prove difficult and controversial, because of problems of
attribution and because New Zealand funders in recent years have played an
important role in determining the priority outputs and inputs which must be
purchased. The paper suggests that accountability is more appropriate at the
output and process level, in addition to holding purchasers accountable for the
ways in which they make decisions and undertake contracting roles. Holding
purchasers accountable for purchasing outputs and processes, however, requires
greater commitment on the part of the funder to setting priorities more clearly;
specifying the range and level of outputs to be purchased and the terms of access
to those services; and funding services to this level. The international
attention currently being paid to the development of practice guidelines and
priority criteria also suggests that holding purchasers accountable for a form of
inputs may become an increasingly common practice in future. From 1 July 1998,
New Zealand will introduce a priority criteria system for determining access to
elective surgery; accountability is thus becoming focused on inputs in the form
of patient characteristics. This approach will greatly assist in promoting
accountability.
PMID- 10187656
TI - Translating health services research into management practice. Interview by
Matthew D. Pavelich.
PMID- 10187657
TI - The efficiency of acute care bed utilization in Newfoundland and Labrador.
AB - Hospital efficiency is closely related to utilization levels and length of stay.
This study determined whether inappropriate bed utilization in Newfoundland was
related to inefficiency or inadequate access to alternative services. It also
compared Canadian Institute for Health information (CIHI) data to our survey to
determine whether they provide comparable information for monitoring efficiency.
Inappropriate acute care days were identified using a modified Appropriateness
Evaluation Protocol. Average length of stay (ALOS) by service for each of the
province's acute care institutions was also reviewed from 1993-94 to 1995-96
using the CIHI database. Hospital admissions were Inappropriate in 14.2 percent
of 2,007 cases. Of the 14,194 days of care, 22.8 percent were inappropriate, with
most (16.4 percent) being avoidable with better use of existing resources. Of the
inappropriate days, 49.2 percent related to physicians' functions. The provincial
ALOS fell from 5.70 days in 1993-94 to 5.39 days in 1995-96, but remains 10.5
percent above the national average.
PMID- 10187658
TI - Efficiency of institutional long-term care and annual demands for placement.
AB - The objective of this study was to determine the efficiency of and annual demands
for institutional long-term care placement in the St. John's region. The study
population comprised all applicants assessed for institutional long-term care
through the Community Health St. John's Region Single Entry System in 1995-96.
The outcome measures used for the study included estimates of client resource
utilization employing the RUGs III and Alberta Resident Classification System;
hospital beds occupied; time to placement; and annual demands on long-term care.
The study concludes that objective criteria for admission to supervised care and
nursing home care may help reduce the number of inappropriate placements (thus
maximizing the use of existing nursing home beds) and decrease annual demands.
Investment in alternatives to nursing home care for those with modest disability
is suggested.
PMID- 10187659
TI - Using the balanced scorecard to align strategy and performance in long-term care.
AB - The Sisters of Charity of Ottawa Health Service (SCOHS) is a Canadian health care
corporation that has adapted Kaplan and Norton's balanced scorecard to enhance
strategic management and measurement in a multisite health care facility
comprising long term care, continuing complex care, rehabilitative services,
palliative care and ambulatory care. This article discusses how the SCOHS has
incorporated the following principles into the balanced scorecard: demonstration
of cause and effect; inclusion of outcomes and performance drivers; linkage to
fiscal and utilization indicators; and integration of the mission and values of
the organization. Examples of corporate level outcomes and performance measures
are provided in the form of lead and lag indicators.
PMID- 10187660
TI - Continuous quality improvement: status of Canadian health care organizations.
AB - The Canadian Council on Health Services Accreditation (CCHSA) surveyed its client
groups to determine how involved they had become in continuous quality
improvement (CQI) activities. This was a follow up to a 1992 survey. Most of the
participating organizations indicated they had adopted a CQI philosophy. A major
factor influencing this decision was the use of the CCHSA's client-centred
standards. This article outlines the gains organizations have realized by
implementing CQI, and the extent to which organizations have implemented CQI
principles, methods and tools. The information from this survey has been used to
develop the accreditation program for the year 2000--"The AIM Project: Achieving
Improved Measurement."
PMID- 10187662
TI - Choices in transition.
PMID- 10187661
TI - Learning to support your work force in changing times.
AB - This article looks at how one health care organization, the Royal Ottawa Health
Care Group, has taken a proactive approach to the human resource challenges
associated with ongoing changes and transitions in the work place. The overriding
objective has been to retain a stable, highly skilled and motivated work force,
which is essential to providing quality care.
PMID- 10187663
TI - Alberta's health care dilemma.
PMID- 10187664
TI - Joint Commission and OSHA receive award for promoting health care workers'
safety.
PMID- 10187665
TI - Standards and survey process FAQs. Health Care Network Accreditation Program.
PMID- 10187666
TI - Standards and survey process FAQs. Home Care Accreditation Program.
PMID- 10187667
TI - Standards and survey process FAQs. Hospital Accreditation Program.
PMID- 10187668
TI - Standards and survey process FAQs. Laboratory Accreditation Program.
PMID- 10187669
TI - Standards and survey process FAQs. Long Term Care Accreditation Program.
PMID- 10187670
TI - Most challenging 1998 standards for five accreditation programs.
PMID- 10187671
TI - Most challenging laboratory standards: how to better comply.
PMID- 10187672
TI - Special report on standards and survey process frequently asked questions (FAQs).
Ambulatory Care Accreditation Program.
PMID- 10187673
TI - Standards and survey process FAQs. Behavioral Health Care Accreditation Program.
PMID- 10187674
TI - The DA's demand: $800,000 from our practice.
PMID- 10187675
TI - They sued for what?!!
PMID- 10187676
TI - If a telephone triage nurse gives bad advice.
PMID- 10187677
TI - Who has the Midas touch?
PMID- 10187678
TI - My "funny" malpractice suit was no laughing matter.
PMID- 10187679
TI - More dollars for doctors?
PMID- 10187680
TI - Tried in the courtroom--malpractice double jeopardy.
PMID- 10187681
TI - Seeing the sickest patients--and getting paid for it.
PMID- 10187682
TI - Doctors overexert themselves jumping to conclusions.
PMID- 10187683
TI - The use of electronic mail at the reference desk: impact of a computer-mediated
communication technology on librarian-client interactions.
AB - Commonly recognized computer-mediated communication (CMC) tools include virtual
environments, bibliographic databases, listservers, newsgroups, group
teleconferencing, interactive messaging systems and electronic mail. The use of
these technologies in libraries has grown exponentially over the past decade.
Electronic mail has emerged as an especially popular communication tool for
librarians, and their colleagues and patrons. This paper explores the use of a
reference department electronic mail service and its impact on reference services
and librarian-client interactions. Several issues related to the implementation
of CMC technologies are presented, including the maintenance and monitoring of
reference electronic mail systems, the types of questions that are typically
posted, and potential barriers to the implementation and use of reference e-mail.
PMID- 10187684
TI - Free medical news and current event Internet sites for medical librarians.
AB - The world of medical advancements is moving at a record pace. New drug approvals,
important discoveries, and the explosion of consumer information on the Web have
prompted health professionals with the need to keep current with the latest news
stories in order to satisfy patient questions. The medical librarian who keeps up
with the latest medical news is a valuable resource for all health professionals.
The following is a compilation of sites for medical news available on the Web.
The sites are limited to those that do not charge a fee and that direct the user
immediately to top health stories, as opposed to requiring the use of a search
feature. This list is not exhaustive; rather, it represents some of the more
common news sources.
PMID- 10187685
TI - Breaking down information barriers: a guide to international research of medical
resources on the World Wide Web.
AB - The purpose of this paper is to facilitate international research of medical
resources on the World Wide Web. International research consists of overcoming a
unique set of obstacles and challenges that are not involved when undertaking
research tasks using only U.S.-based information. Utilizing the World Wide Web
can help us to overcome most of the restraints we would have to face when we
perform research outside of our local geography. Currently, there are a number of
Internet Web sites that may assist us in breaking down the barriers to
undertaking international research.
PMID- 10187686
TI - Medical insurance on the Internet: benefits and information at your fingertips.
PMID- 10187687
TI - Internet in the workplace: censorship, liability, and freedom of speech.
AB - Most hospital medical libraries are supported by private, corporate funds and
thus fall under the corporation's policies in regard to discrimination,
harassment, and sexual harassment. With the free flow of information available on
the Internet and through e-mail, it is mandatory to create a corporate policy for
appropriate use and review of materials. Access to "questionable" or
inappropriate Internet sites is not a freedom of speech issue in a private
corporation; it is a potential liability for the corporation, the library, and
the librarian. It is also a misuse of company resources.
PMID- 10187688
TI - Meeting the information needs of students and professionals: the Health
Informatics Education Center at the Houston Academy of Medicine-Texas Medical
Center Library.
PMID- 10187689
TI - Civil law or higher law? Cases test legal exemptions for religious hospitals.
PMID- 10187690
TI - Here's the plan. AHA offers Medicare changes to federal commission.
PMID- 10187691
TI - Private hospitals join tobacco war.
PMID- 10187692
TI - Medical records woes. Critics assail outsourcing firms for high prices.
PMID- 10187693
TI - Knowing the score. Mass. hospitals find out how patients rated them.
PMID- 10187694
TI - Survey: HMO premiums rising sharply.
PMID- 10187695
TI - AHA approves dues hike. Board votes to increase institutional member dues.
PMID- 10187696
TI - Docs unite on cutback. Negative cost-growth target may heal split for now.
PMID- 10187697
TI - The VA on the firing line. Veterans groups oppose privatization despite a
dwindling patient population, high costs.
AB - Demographic trends raise some uncomfortable questions for the VA and Congress.
For example, should American taxpayers continue financing a government-owned and
operated healthcare system that spends $17.3 billion a year and serves a
shrinking population, when the government could buy the same care in the private
sector? Some say the solution is to privatize the VA.
PMID- 10187698
TI - Hans and Franz go gray. Nursing homes try weight training for the frail elderly.
PMID- 10187699
TI - Taking on a tough crowd. Premier tries to cut costs on docs' preferred devices.
PMID- 10187700
TI - Capital punishment. Equity drought hits technology and service firms.
PMID- 10187701
TI - Exodus may continue. Legal quirk may allow more HMOs to exit Medicare.
PMID- 10187702
TI - A spur for PSOs. North Carolina law eases regulatory burdens.
PMID- 10187703
TI - A tarnished model? Moody's report hits D.C. hospital's losses, leadership.
PMID- 10187704
TI - Anti-hepatitis push raises ethical issues.
PMID- 10187705
TI - Running for cover? Doctors seeking practices away from managed care.
PMID- 10187706
TI - A financial checkup for radiology services. Managers need comprehensive data to
diagnose the shape of their departments.
AB - Radiologists make their living interpreting murky X-rays and snowy ultrasound
exams. Administrators often make decisions about managing radiology services in a
similar way, with only a hazy idea of how to improve financial operations.
Decisions about which procedures are profitable and which lose money require
data. But that information is often in short supply.
PMID- 10187707
TI - The advice game. Layoffs, a need for change push execs into consulting.
PMID- 10187708
TI - Paying for the crime. Wis. law requires providers to do background checks.
PMID- 10187709
TI - A 'health imperative.' Happiest groups integrate IT into business strategy.
PMID- 10187710
TI - Province breaks the mold. For-profit company finds success in nonurban markets.
PMID- 10187711
TI - Getting down to business. Medicare reform group expected to suggest changes.
PMID- 10187712
TI - Slapped hands. Hospital is rebuked for marketing against competitor.
PMID- 10187713
TI - Rumble in L.A. CMA lawsuit tests corporate practice of medicine.
PMID- 10187714
TI - Agreeing on differences. Commission advocates greater diversity among healthcare
professionals.
PMID- 10187716
TI - The revenues blues. AHA's new dues hike comes as income heads south.
PMID- 10187717
TI - AHERF vs. AHERF. System's own hospitals, led by ex-CEO, now its creditors.
PMID- 10187715
TI - The quiet restructuring. Blaming feds, hospitals shed workers, facilities in
droves.
AB - A major downsizing is under way in the hospital industry. Hospitals are laying
off thousands of workers and closing down a variety of services. Facilities cite
the usual suspects for taking such drastic action: managed care, reimbursement
changes in federal healthcare programs, plummeting inpatient loads and
consolidation. This is the first in a two-part series on financial turmoil in the
industry.
PMID- 10187718
TI - Taking a hike. To stay viable, Kaiser raises premium rates by 20%.
PMID- 10187719
TI - Healthcare groups pay big for lobbying.
PMID- 10187720
TI - The nurse rush. Providers spare no expense for suddenly scarce workers.
PMID- 10187721
TI - The price of secrecy. Failure to be forthcoming with financial data could prove
costly for bond issuers.
PMID- 10187722
TI - A cautionary tale. Md. hospitals join ranks of money-losers on PPMs.
PMID- 10187723
TI - 'What's in it for me?' Incentive programs for physicians can improve outcomes.
PMID- 10187724
TI - A giant continues to grow. Aetna to buy Prudential HealthCare for $1 billion.
PMID- 10187725
TI - Showing improvement is a must for 1999 survey.
PMID- 10187726
TI - Routine CABG in 3 hours: systems make it possible.
PMID- 10187727
TI - Blaming not point in sentinel event.
PMID- 10187728
TI - JCAHO's tips on wrong-site surgery risks.
PMID- 10187729
TI - Stays are shorter in Phase I PACU (postanesthesia care unit). Interview by Norra
Macready.
PMID- 10187730
TI - Reuse of single-use items raises difficult questions.
PMID- 10187731
TI - Rules aim to boost organ donation.
PMID- 10187732
TI - Self-management works for PACU (postanesthesia care unit). Interview by Judith M.
Mathias.
PMID- 10187733
TI - Why do we use chemical indicators?
PMID- 10187734
TI - A map for leading through change.
PMID- 10187735
TI - Fine levied after hysteroscopy death.
PMID- 10187736
TI - High court defines harassment liability.
PMID- 10187737
TI - Mezzanine financing bridges mortgage gap.
PMID- 10187738
TI - Putting CQI to work.
PMID- 10187739
TI - Don't let the Y2K bug bite.
PMID- 10187740
TI - Researches attack Alzheimer's on many fronts.
PMID- 10187741
TI - Agency opts for outcomes over process.
PMID- 10187742
TI - In the public eye. An industry takes charge of its image.
PMID- 10187743
TI - Designing of Alzheimer's centers. Using design elements that accommodate
functional needs.
PMID- 10187744
TI - ACHA 1998 Quality Award winners. Quality initiatives that stand out.
PMID- 10187745
TI - ACHA Quality Award. 1998 Nurse Scholarship Award winners.
PMID- 10187746
TI - Avoiding sales tax overpayments.
PMID- 10187747
TI - Characterization of tolbutamide polymorphs (Burger's forms II and IV) and
polymorphic transition behavior.
AB - Burger's two polymorphs of tolbutamide (TB), an oral hypoglycemic agent, were
obtained by spray-drying the drug dissolved in a mixed solvent of
ethanol/dichloromethane (Form IV) and allowing Form IV to stand at constant
temperatures and humidities (Form II). These polymorphs were characterized by
various physical methods [e.g., powder X-ray diffractometry, differential
scanning calorimetry, infrared spectrometry, and solid-state carbon-13 nuclear
magnetic resonance (13C NMR) spectroscopy] and compared with two other TB
polymorphs Forms I and III. The 13C NMR spectra showed that the chemical shift
and the peak shape of resonance associated with the toluene and n-butyl moieties
of TB were different for each of the four polymorphs, whereas the carbonyl carbon
was unchanged, indicating different conformations and molecular motions of the
toluene and n-butyl moieties in the solid states. Form IV converted itself to
Form II within 3 h when it was stored at 45 degrees C and 75% relative humidity
(RH) and, in turn, Form II transformed to Form I at higher temperatures. The
conversion of Form IV to Form II proceeded according to a zero-order equation
(Polany-Winger equation), and that of Form II to Form I according to a first
order equation. The increase in RH accelerated the polymorphic transition of Form
IV. Both the apparent dissolution rate and the solubility of Form IV were nearly
identical with those of Form II, because the former changed to the latter during
the dissolution, but their dissolution rates and solubility were higher than
those of Forms I and III. These dissolution characteristics of TB polymorphs were
reflected in the oral absorption behavior in dogs; that is, the bioavailability
increased in the order Form I < Form III < Form II approximately Form IV.
PMID- 10187748
TI - Transport of the delta-opioid receptor agonist [D-penicillamine2,5] enkephalin
across the blood-brain barrier involves transcytosis1.
AB - The delta opioid receptor antagonist [D-penicillamine2,5]enkephalin (DPDPE) is an
enzymatically stable peptide analogue of Met-enkephalin. DPDPE uses a saturable
transport mechanism to cross the blood-brain barrier (BBB), though the exact
mechanism is not fully understood. The aim of the present study was to identify
the mechanism by which DPDPE enters the brain. The effect of phenylarsine oxide
(PAO), an endocytosis inhibitor, on the transport of [3H]DPDPE was investigated
using both in vitro and in situ transport studies. Two in vitro models of the BBB
utilizing primary bovine brain microvascular endothelial cells (BBMEC) were
studied. [3H]DPDPE permeability across monolayers of BBMEC grown on polycarbonate
filters was studied. PAO significantly reduced the permeability of [3H]DPDPE
across the monolayer. PAO also reduced the uptake of [3H]DPDPE into BBMEC cells,
without affecting binding to the cells. The in situ perfusion model of the BBB
was also studied, PAO reduced DPDPE uptake by the brain in a dose-dependent
manner. These studies indicate that DPDPE enters the brain via an energy
dependent transcytotic mechanism.
PMID- 10187749
TI - Validation of a biophysical drug absorption model by the PATQSAR system.
AB - Absorption rate constants (in situ rat gut technique) and in vitro antibacterial
activities of twenty fluoroquinolones have been evaluated. A biophysical model
that relates the absorption of the compounds with their lipophilicity was fitted.
The model considers the absorption process from the intestinal lumen as the sum
of two resistances in series: aqueous diffusional barrier and lipoidal membrane.
Even if partitioning into the membrane and membrane diffusion are both enhanced
for lipophilic compounds, the absorption rate constant is limited by the aqueous
diffusion. To estimate the influence of structural modifications on each property
and to establish the role of lipophilicity in controlling in situ absorption and
in vitro antibacterial activity, the PATQSAR search system is used to construct
structure-property relationships. The structural models, which explain 99% of the
total variance of each physicochemical property and 96% of each in vitro
biological activity, provide an explicit and precise interpretation of
lipophilicity, absorption, and antimicrobial activity. The results confirm the
important role of lipophilicity in controlling absorption, as pointed out by the
biophysical model for the piperazinyl series, and suggest the introduction of
electronic factors in order to extend the model to heterologues. They also
justify the mechanism by which quinolones are assumed to induce antibacterial
activity.
PMID- 10187750
TI - Colloidal and thermal characteristics of concentrated dispersions of
polymethacrylate-based latices for aqueous enteric coating.
AB - We have used rheological and thermal methods to study the colloidal
characteristics of a widely used technical latex. The dispersions of
poly(methacrylic acid-ethyl acrylate) (Eudragit L100-55) were found to be
stabilized by a combination of electrostatic and steric mechanisms termed as
electrosteric stabilization. The electrosteric stabilization is considered to
arise in part from dissolved polymer chains with charged carboxylic groups
extending out into the continuous phase. The presence of dissolved polymer chains
in the dispersion implies that coalescence and interpenetration will be
facilitated during film formation, enabling a smooth continuous film to be
formed. The extent of the stabilization layer and an effective hard-sphere volume
was estimated to discuss the steady shear and viscoelastic properties in this
context. The glass transition temperature (Tg) of the particles making up the
dispersion has also been determined as a function of sorbed moisture and modeled
by the Gordon-Taylor equation modified for specific interaction between water,
surfactant, and polymer. This parameter at high moisture content can be used as a
first approximation to the minimum film-forming temperature (MFT). Change in Tg
(and thus MFT) with moisture content implies that the coating process must be
controlled so as to produce a rate of drying slow enough to allow coalescence to
occur.
PMID- 10187751
TI - In vitro investigation of ionic polysaccharide microspheres for simultaneous
delivery of chemosensitizer and antineoplastic agent to multidrug-resistant
cells.
AB - Insufficient intratumoral concentration of therapeutic agents and multidrug
resistance are major factors responsible for failure of treatment of solid
tumors. Simultaneous delivery of chemosensitizing and antineoplastic agents by
microspheres could lead to enhanced chemotherapy of multidrug-resistant (MDR)
tumors. Ionic polysaccharide microspheres derived from dextran were used to load
chemosensitizers (e.g., verapamil) and anticancer drugs such as vinblastine. High
drug loading was achieved for both a single agent and dual agents. The
equilibrium drug loading was dependent on the ratio of the microspheres (MS) to
the drug, as well as the relative affinity of the agents to the MS in the case of
dual agents. The drug release from drug-MS involved hydration and swelling of the
MS in addition to ion exchange. The effectiveness of MS-delivered
chemosensitizers in the reversal of drug resistance was evaluated by measuring
the uptake of [3H]vinblastine by MDR cells (CHRC5). The concomitant delivery of
verapamil with vinblastine by the MS led to a 6-7-fold increase in the uptake of
vinblastine, a level similar to the uptake obtained with free drug solutions. The
results suggest that the antineoplastic and chemosensitizing agents were released
effectively from the MS and the bioactivity of the chemosensitizer was preserved
during the process.
PMID- 10187752
TI - Pore induction in human epidermal membrane during low to moderate voltage
iontophoresis: A study using AC iontophoresis.
AB - The present study aimed to investigate new pore induction as a flux-enhancing
mechanism in human epidermal membrane (HEM) with low to moderate voltage electric
fields. The extent of pore induction and the effective pore sizes of these
induced pores were to be assessed using a low frequency (12.5 Hz) low to moderate
voltage (2. 0 to 4.0 V) square-wave alternating current (ac) "passive" permeation
method (ac iontophoresis). This ac approach was to allow for inducing and
sustaining a state of pore induction in HEM while permitting no significant
transport enhancement via electroosmosis; thus, transport enhancement entirely
due to new pore induction (enhanced passive permeation) was to be assessed
without any contributions from electroosmosis. Good proportionality between the
increase in HEM permeability and its electrical conductance was found with the
"passive" transport data obtained during square-wave ac iontophoresis using urea
as the model permeant. Typically, at 3.0 to 4.0 V, HEM conductance increases (and
permeability increases) ranged from around 3- to 30-fold. These results appear to
be the first direct evidence that new pore induction in HEM is a significant flux
enhancing mechanism under moderate voltage conditions. The extents of pore
induction in HEM under low frequency moderate voltage (2.0 to 3.0 V) ac, pulsed
direct current (dc), and continuous dc were also compared. The extents of pore
induction from square-wave ac and pulsed dc were generally of the same order of
magnitude but somewhat less than that observed during continuous dc iontophoresis
at the same applied voltage and duration, suggesting less extent of pore
induction with reversing polarity or when a brief delay is provided between
pulses to allow for membrane depolarization. The average effective pore sizes
calculated for the induced pores from the experimental data with urea and
mannitol as probe permeants and the hindered transport theory were 12 +/- 2 A,
which are of the same order of magnitude as those of preexisting pores determined
from conventional passive diffusion experiments.
PMID- 10187753
TI - Chemical stability of an ester prodrug of a glycoprotein IIb/IIIa receptor
antagonist in solid dosage forms.
AB - DMP 754 is an ester prodrug of a glycoprotein IIb/IIIa receptor antagonist that
undergoes ester and amidine hydrolysis in the presence of excipients. A means for
the stabilization of DMP 754 was needed for the formulation of a stable drug
product. Incorporation of a pH modifier in the formulation was used to control
the microenvironment pH to coincide with that of maximum stability for DMP 754.
Stability of tablets and capsules manufactured by (a) trituration process, (b)
dry granulation process, and (c) wet granulation process was evaluated in HDPE
bottles. Formulations manufactured by the dry and wet granulation processes
contained disodium citrate as the pH modifier. Although aqueous wet granulation
of a hydrolyzable drug is usually avoided, tablets and capsules manufactured by
wet granulation were more stable in this case than those manufactured by the dry
granulation process. This was attributed to the more uniform distribution of the
pH modifier. Although the compression process resulted in enhanced degradation of
the binary blend of DMP 754 and anhydrous lactose, tablets manufactured by the
wet granulation process were more stable than capsules manufactured by the same
process. Decreasing excipient-to-drug ratio enhanced the stability of tablets
manufactured by the wet granulation process.
PMID- 10187754
TI - Dissolution specifications based on release rates.
AB - A procedure based on release rates is proposed for the establishment of
dissolution specifications that ensure the bioequivalence of a test and a
reference product. This procedure, which confines Cmax (the maximum concentration
of the drug in vivo) and AUCinfinity (the area under the time-concentration
curve, extrapolated to infinity) values within any desired range (relative to a
reference product), can be used as an alternative to the methods presented in the
FDA guidance1 or the USP.2 The method is appropriate for zero-order or first
order release products with linear Level A in vitro/in vivo correlations (IVIVC).
Based on the result that the relative difference in Cmax must always be smaller
than the relative difference in the absorption rate constants (for any test and
reference products of a given drug), the "minimum range" specifications are set.
These specifications, which are identical for both zero-order and first-order
release products, are of general validity. They depend only on the relative
extents of release, but are otherwise drug or formulation independent. For
certain extended release products demonstrating a constant release rate that is
unaffected by dissolution conditions (thus allowing the assumption of Level A
IVIVC), the "minimum range" dissolution limits are applicable even when in vivo
data is not available. If the reference product in vivo data is available, wider
limits (which are product specific) may be set. If the drug disposition is
monoexponential, the specifications generated are the widest possible. They are
termed the "ideal" specifications. In the case of a multiexponential disposition,
the limits set by the procedure will (generally) not be the widest possible.
Although the method is based on one-compartment models, it is essentially model
independent in the sense that microscopic modeling is redundant for its
application.
PMID- 10187755
TI - Uptake and excretion of sodium taurocholate by the isolated perfused neonatal
sheep liver.
AB - We present a model for perfusion of the isolated perfused neonatal sheep liver
which allows examination of drug disposition by the intact organ. We studied the
disposition of sodium taurocholate (TC) in seven neonatal lambs (ages 2-11 days)
and compared the results with earlier data from the perfused fetal sheep liver
(Ring, J. A. et al. Biochem. Pharmacol. 1994, 48, 667-674). Measurements of
perfusion pressure, oxygen consumption, lactate:pyruvate ratio, bile flow, and
liver histology indicated that the preparation was both viable and stable over a
2 h period. [14C]-labeled TC was added to the reservoir by constant infusion (30
micromol/h) and the ductus venosus shunt quantitated by injection of [153Gd]
labeled microspheres. Shunt-corrected hepatic extraction ratio of TC was 0. 56 +/
0.14 (fetal 0.23 +/- 0.16, p < 0.005) and clearance of TC was 0.92 +/- 0.35
mL/min/g liver (fetal 0.44 +/- 0.23 mL/min/g, p < 0. 01). We conclude that the
isolated perfused neonatal sheep liver is a useful experimental model which will
facilitate the study of the developmental physiology and pharmacology of the
liver. There is considerable maturation of the biliary excretion of TC between
the late fetal and early neonatal periods in the lamb.
PMID- 10187756
TI - Comparison of the biodistribution in mice of 111indium oxine encapsulated into
poly(lactic-co-glycolic)-D,L-85/15 and poly(epsilon caprolactone) nanocapsules.
AB - Poly(lactic-co-glycolic)-D,L-85/15 (PLAGA) nanocapsules and poly(epsilon
caprolactone) (PCL) nanocapsules were labeled with a relatively long half-life
compound that is usually used in humans; that is, 111In-labelled oxine (111In
oxine). This labeling technique led to a high 111In oxine entrapment efficiency
and good stability during dialysis against phosphate buffer and phosphate
buffered albumin solution. Because of these characteristics, the nanocapsules
biodistribution was followed up after intravenous administration for up to 96 h
by determining the gamma activity in the tissues after sampling. The
administration of the PCL-encapsulated 111In oxine led to a decrease in the blood
radioactivity and an increase in the liver radioactivity compared with the
solution. This effect was even more pronounced with the PLAGA nanocapsules.
Finally, the activity level in other tissues, such as the kidneys, the lungs, and
the spleen, appeared to be rather low and only slightly affected by the
encapsulation into one or the other polymer.
PMID- 10187757
TI - Effect of surface charge on the stability of oil/water emulsions during steam
sterilization.
AB - Intravenous lipid emulsions are used for total parenteral nutrition and as
carriers for lipophilic drugs. Exposure to the high temperature (121 degrees C)
required for steam sterilization may cause coalescence and an increase in droplet
size. The purpose of this study was to investigate whether an increase in the
electrostatic repulsive force between oil droplets produced by formulation
modification improves the thermal stability of lipid emulsions during
autoclaving. The addition of a small amount, 0.66 or 1.32 mmol/kg (mm), of
purified anionic phospholipid fractions (phosphatidic acid, phosphatidylglycerol,
or phosphatidylinositol) to the standard formula increased the zeta potential
from its normal value of -11 mV to -39 mV. Emulsions with the larger negative
zeta potential did not exhibit any change in oil droplet size or distribution
during steam sterilization at 121 degrees C for 15 min. The autoclaved emulsions
having the larger negative zeta potential did not exhibit any evidence of
coalescence when samples were stored for 1 month at 4 degrees C, room
temperature, or 40 degrees C. Reduction of the negative surface charge of the oil
droplets by the addition of stearylamine confirmed that the surface charge was an
important factor, as emulsions having a reduced negative surface charge separated
into two phases during autoclaving.
PMID- 10187758
TI - Cocaine and alcohol interactions in the rat: effect on cocaine pharmacokinetics
and pharmacodynamics.
AB - The effect of alcohol coadministration on cocaine pharmacokinetics and
pharmacodynamics was investigated in awake, freely moving rats. Cocaine plasma
and brain extracellular fluid (ECF) concentration-time profiles were
characterized after intraperitoneal (ip) administration of 30 mg/kg cocaine to
rats that were pretreated with either normal saline or alcohol at 5 g/kg in a
balanced crossover experimental design. The neurochemical response to cocaine
administration, measured as the change in dopamine concentration in the nucleus
accumbens (N ACC) and the change in the mean arterial blood pressure were
monitored simultaneously. Intragastric alcohol administration significantly
increased cocaine systemic bioavailability after ip administration from 0.550 +/-
0.044 to 0. 754 +/- 0.071. Also, the absorption rate constant increased from 0.
199 +/- 0.045 to 0.276 +/- 0.059 min-1 due to alcohol coadministration; however,
this increase was not significant. Alcohol inhibition of cocaine metabolism
caused an increase in cocaine elimination half-life from 26.3 +/- 3.6 to 40.0 +/-
8.1 min. Also, cocaine tissue distribution was enhanced by alcohol, resulting in
a significant increase in cocaine volume of distribution. Analysis of the brain
cocaine concentration-neurochemical effect relationship by the sigmoid-Emax
pharmacodynamic model showed that Emax increased from 850 +/- 200 to 1550 +/-
640% of baseline due to alcohol coadministration, whereas EC50 decreased from
3400 +/- 580 to 2000 +/- 650 ng/mL, indicating higher cocaine potency in the
presence of alcohol. The estimates of the indirect inhibitory pharmacodynamic
model used to examine the plasma cocaine concentration-change in blood pressure
relationship were not significantly different after the two treatments. These
results indicate that alcohol significantly alters cocaine absorption,
distribution, and elimination, resulting in higher and prolonged cocaine plasma
concentration. Alcohol coadministration also potentiates the neurochemical
response to cocaine administration.
PMID- 10187759
TI - Cocaine and alcohol interactions in the rat: contribution of cocaine metabolites
to the pharmacological effects.
AB - The pharmacokinetics and pharmacodynamics of cocaine and its three metabolites,
benzoylecgonine, norcocaine, and cocaethylene, were investigated in awake, freely
moving rats. This work was performed to examine the effect of alcohol
coadministration on the metabolic profile of cocaine and to determine the
contribution of cocaine metabolites to the pharmacological responses observed
after cocaine administration. The plasma and brain extracellular fluid
concentration-time profiles were characterized after intravenous (iv)
administration of cocaine and the three metabolites in a crossover experimental
design. The neurochemical response, measured as the change in dopamine
concentration in the nucleus accumbens, and the cardiovascular responses,
measured as the change in the mean arterial blood pressure, heart rate, and QRS
interval, were monitored simultaneously. Cocaethylene had the highest brain-to
plasma distribution ratio, followed by cocaine, norcocaine, and benzoylecgonine.
The estimated total body clearances for cocaine, benzoylecgonine, norcocaine, and
cocaethylene were 140 +/- 19, 14.7 +/- 1.2, 130 +/- 19, and 111 +/- 16 mL/min/kg,
respectively. Alcohol coadministration increased the formation of norcocaine,
decreased the formation of benzoylecgonine, and resulted in the formation of the
pharmacologically active metabolite cocaethylene. When cocaine was administered
with alcohol, 12.9 +/- 3.1% to 15.3 +/- 2.9% of the cocaine dose was converted to
cocaethylene. Benzoylecgonine did not have any central nervous system or
cardiovascular activities after iv administration. Compared with cocaine,
norcocaine and cocaethylene had more potent and prolonged effects on the
neurochemical, heart rate, and QRS interval responses, and were equipotent in
increasing the mean arterial blood pressure. These results indicate that changes
in the cocaine metabolic profile and the formation of the pharmacologically
active metabolite cocaethylene are, at least partially, responsible for the more
intense and longer lasting effects reported after using this drug in combination
with alcohol.
PMID- 10187760
TI - Influence of calcium ions on the structure and stability of recombinant human
deoxyribonuclease I in the aqueous and lyophilized states.
AB - The effect of calcium ions on the structure and stability of recombinant human
DNase I (rhDNase) in the aqueous and solid (lyophilized) states was investigated.
Fourier transform infrared (FTIR) spectroscopy was used to examine the overall
secondary structure, while chemical stability was monitored in terms of
deamidation and soluble aggregate formation at 40 degrees C. The exogenous
calcium was removed by EGTA. This process can remove all but approximately one
calcium ion per protein molecule. Analysis of the FTIR spectra in the amide III
region in either the aqueous or lyophilized state demonstrated that removal of
exogenous Ca2+ by EGTA-treatment had little effect on the secondary structure
(and lyophilization-induced rearrangement thereof). For the aqueous solution,
circular dichroism was used as an independent technique and confirmed that there
was no large overall change in the secondary or tertiary structure upon the
removal of calcium. The primary degradation route for the aqueous protein was
deamidation. For the EGTA-treated protein, there was also severe covalent
aggregation, e.g., formation of intermolecular disulfides facilitated by the
cleavage of Cys173-Cys209. The aggregates exhibited a markedly different
secondary structure compared to the native protein. For instance, the beta-sheet
band observed at ca. 1620 cm-1 wavenumber in the amide I second derivative
spectra was increased. Enzymatic activity was completely lost upon aggregation,
consistent with the cleavage of the aforementioned native disulfide. For the
protein lyophilized in the presence of Ca2+, there was no increase in deamidated
species during solid-state storage; however, some aggregation was observed. For
the lyophilized EGTA-treated protein, aggregation was even more pronounced, and
there was some loss in enzymatic activity upon reconstitution. Thus, the removal
of calcium ions by EGTA-treatment decreased the stability of rhDNase in both the
aqueous and solid states even though no large overall calcium-induced structural
changes could be observed by the techniques used in this study.
PMID- 10187761
TI - Atmospheric oxidation of poly(oxyethylene) alcohols. Identification of
ethoxylated formates as oxidation products and study of their contact allergenic
activity.
AB - Ethoxylated alcohols are widely used as surfactants. In the present study we have
continued our investigations on the degradation with time upon air exposure of
the ethoxylated alcohols at normal storage and handling. As a result, a new group
of ethoxylated formates with the general formula C12H25(OCH2CH2)nOCHO (n = 0-4)
was identified in C12H25(OCH2CH2)5OH stored and handled at room temperature. To
facilitate the identification work, reference compounds were synthesized. The
formates showed no allergenic activity in the sensitization studies performed. In
previous investigations on the same ethoxylated alcohol, we have identified
formaldehyde and ethoxylated aldehydes among the oxidation products formed.
Formaldehyde is a common contact allergen, and the ethoxylated aldehydes were
shown to have a sensitizing capacity of the same magnitude as formaldehyde. The
instability of the ethoxylated alcohols and formation of oxidation products may
give an allergenic contribution to hand eczema caused by work with water and
surfactants. To investigate the clinical significance in man an appropriate
diagnostic patch testing in exposed humans is required.
PMID- 10187762
TI - Phosphatidylinositol phosphate kinases, a multifaceted family of signaling
enzymes.
PMID- 10187763
TI - Characterization of DorC from Rhodobacter capsulatus, a c-type cytochrome
involved in electron transfer to dimethyl sulfoxide reductase.
AB - The dorC gene of the dimethyl sulfoxide respiratory (dor) operon of Rhodobacter
capsulatus encodes a pentaheme c-type cytochrome that is involved in electron
transfer from ubiquinol to periplasmic dimethyl sulfoxide reductase. DorC was
expressed as a C-terminal fusion to an 8-amino acid FLAG epitope and was purified
from detergent-solubilized membranes by ion exchange chromatography and
immunoaffinity chromatography. The DorC protein had a subunit Mr = 46,000, and
pyridine hemochrome analysis indicated that it contained 5 mol heme c/mol DorC
polypeptide, as predicted from the derived amino acid sequence of the dorC gene.
The reduced form of DorC exhibited visible absorption maxima at 551.5 nm (alpha
band), 522 nm (beta-band), and 419 nm (Soret band). Redox potentiometry of the
heme centers of DorC identified five components (n = 1) with midpoint potentials
of -34, -128, -184, -185, and -276 mV. Despite the low redox potentials of the
heme centers, DorC was reduced by duroquinol and was oxidized by dimethyl
sulfoxide reductase.
PMID- 10187764
TI - Rapid inactivation of NOS-I by lipopolysaccharide plus interferon-gamma-induced
tyrosine phosphorylation.
AB - Human astrocytoma T67 cells constitutively express a neuronal NO synthase (NOS-I)
and, following administration of lipopolysaccharide (LPS) plus interferon-gamma
(IFNgamma), an inducible NOS isoform (NOS-II). Previous results indicated that a
treatment of T67 cells with the combination of LPS plus IFNgamma, by affecting
NOS-I activity, also inhibited NO production in a very short time. Here, we
report that under basal conditions, a NOS-I protein of about 150 kDa was weakly
and partially tyrosine-phosphorylated, as verified by immunoprecipitation and
Western blotting. Furthermore, LPS plus IFNgamma increased the tyrosine
phosphorylation of NOS-I, with a concomitant inhibition of its enzyme activity.
The same effect was observed in the presence of vanadate, an inhibitor of
phosphotyrosine-specific phosphatases. On the contrary, genistein, an inhibitor
of protein-tyrosine kinases, reduced tyrosine phosphorylation of NOS-I, enhancing
its enzyme activity. Finally, using reverse transcriptase-polymerase chain
reaction, we have observed that a suboptimal induction of NOS-II mRNA expression
in T67 cells was enhanced by vanadate (or L-NAME) and inhibited by genistein.
Because exogenous NO has been found to suppress NOS-II expression, the decrease
of NO production that we have obtained from the inactivation of NOS-I by
LPS/IFNgamma-induced tyrosine phosphorylation provides the best conditions for
NOS-II expression in human astrocytoma T67 cells.
PMID- 10187765
TI - Requirement of phosphatidylinositol 3-kinase activity for bradykinin stimulation
of NF-kappaB activation in cultured human epithelial cells.
AB - The signaling mechanisms utilized by bradykinin (BK) to activate the
transcription factor nuclear factor kappaB (NF-kappaB) are poorly defined. We
previously demonstrated that BK-stimulated NF-kappaB activation requires the
small GTPase RhoA. We present evidence that BK-induced NF-kappaB activation both
activates and requires phosphatidylinositol 3-kinase (PI 3-kinase) in A549 human
epithelial cells. Pre-treatment with the PI 3-kinase-specific inhibitors,
wortmannin, and LY294002 effectively blocked BK-induced PI 3-kinase activity.
Wortmannin and LY294002 also abolished BK-induced NF-kappaB activation, as did
transient transfection with a dominant negative mutant of the p85 subunit. BK
stimulated PI 3-kinase activity and NF-kappaB activation were sensitive to
pertussis but not cholera toxin, suggesting that the B2 BK receptors transducing
the response were coupled to Galphai or Galphao heterotrimeric G proteins. Tumor
necrosis factor alpha (TNFalpha) also stimulated increased PI 3-kinase activity,
however TNFalpha-stimulated NF-kappaB activation was not affected by the PI 3
kinase inhibitors or the p85 dominant negative mutant. These findings provide
evidence that BK-induced NF-kappaB activation utilizes a signaling pathway that
requires activity of both RhoA and PI 3-kinase and is distinct from the signaling
pathway utilized by TNFalpha. Furthermore, we show that the p85 regulatory
subunit is required for activation of PI 3-kinase activity by this G protein
coupled receptor.
PMID- 10187766
TI - Evidence of a cyclooxygenase-related prostaglandin synthesis in coral. The allene
oxide pathway is not involved in prostaglandin biosynthesis.
AB - Certain corals are rich natural sources of prostaglandins, the metabolic origin
of which has remained undefined. By analogy with the lipoxygenase/allene oxide
synthase pathway to jasmonic acid in plants, the presence of (8R)-lipoxygenase
and allene oxide synthase in the coral Plexaura homomalla suggested a potential
metabolic route to prostaglandins (Brash, A. R., Baertshi, S. W., Ingram, C.D.,
and Harris, T. M. (1987) J. Biol. Chem. 262, 15829-15839). Other evidence, from
the Arctic coral Gersemia fruticosa, has indicated a cyclooxygenase intermediate
in the biosynthesis (Varvas, K., Koljak, R., Jarving, I., Pehk, T., and Samel, N.
(1994) Tetrahedron Lett. 35, 8267-8270). In the present study, active
preparations of G. fruticosa have been used to identify both types of arachidonic
acid metabolism and specific inhibitors were used to establish the enzyme type
involved in the prostaglandin biosynthesis. The synthesis of prostaglandins and
(11R)-hydroxyeicosatetraenoic acid was inhibited by mammalian cyclooxygenase
inhibitors (indomethacin, aspirin, and tolfenamic acid), while the formation of
the products of the 8-lipoxygenase/allene oxide pathway was not affected or was
increased. The specific cyclooxygenase-2 inhibitor, nimesulide, did not inhibit
the synthesis of prostaglandins in coral. We conclude that coral uses two
parallel routes for the initial oxidation of polyenoic acids: the cyclooxygenase
route, which leads to optically active prostaglandins, and the
lipoxygenase/allene oxide synthase metabolism, the role of which remains to be
established. An enzyme related to mammalian cyclooxygenases is the key to
prostaglandin synthesis in coral. Based on our inhibitor data, the catalytic site
of this evolutionary early cyclooxygenase appears to differ significantly from
both known mammalian cyclooxygenases.
PMID- 10187768
TI - Biochemical characterization of the small heat shock protein IbpB from
Escherichia coli.
AB - Escherichia coli IbpB was overexpressed in a strain carrying a deletion in the
chromosomal ibp operon and purified by refolding. Under our experimental
conditions, IbpB exhibited pronounced size heterogeneity. Basic oligomers,
roughly spherical and approximately 15 nm in diameter, interacted to form larger
particles in the 100-200-nm range, which themselves associated to yield loose
aggregates of micrometer size. IbpB suppressed the thermal aggregation of model
proteins in a concentration-dependent manner, and its CD spectrum was consistent
with a mostly beta-pleated secondary structure. Incubation at high temperatures
led to a partial loss of secondary structure, the progressive exposure of
tryptophan residues to the solvent, the dissociation of high molecular mass
aggregates into approximately 600-kDa oligomers, and an increase in surface
hydrophobicity. Structural changes were reversible between 37 and 55 degrees C,
and, up to 55 degrees C, hydrophobic sites were reburied upon cooling. IbpB
exhibited a biphasic unfolding trend upon guanidine hydrochloride (GdnHCl)
treatment and underwent comparable conformational changes upon melting and during
the first GdnHCl-induced transition. However, hydrophobicity decreased with
increasing GdnHCl concentrations, suggesting that efficient exposure of
structured hydrophobic sites involves denaturant-sensitive structural features.
By contrast, IbpB hydrophobicity rose at high NaCl concentrations and increased
further at high temperatures. Our results support a model in which temperature
driven conformational changes lead to the reversible exposure of normally
shielded binding sites for nonnative proteins and suggest that both
hydrophobicity and charge context may determine substrate binding to IbpB.
PMID- 10187767
TI - The nucleocapsid protein of murine hepatitis virus type 3 induces transcription
of the novel fgl2 prothrombinase gene.
AB - Using a set of parental and recombinant murine hepatitis virus strains, we
demonstrate that the nucleocapsid protein induces transcription of the novel fgl2
prothrombinase gene and elevated procoagulant activity in those strains that
produce fulminant hepatitis. Chinese hamster ovary cells cotransfected with a
construct expressing nucleocapsid protein from susceptible strains and with a
luciferase reporter construct containing the fgl2 promoter showed a 6-fold
increase in luciferase activity compared with nontransfected cells or cells
cotransfected with a construct expressing nucleocapsid protein from resistant
strains. Two deletions found at coding sites 111-123 and 1143-1145 of structural
domains I and III, respectively, of the nucleocapsid gene may account for the
differences between pathogenic and nonpathogenic strains. Preliminary mapping of
the fgl2 promoter has defined a region from -372 to -306 upstream from the ATG
translation initiation site to be responsive to nucleocapsid protein. Hence,
mapping of genetic determinants in parental and recombinant strains demonstrates
that the nucleocapsid protein of strains that induce fulminant hepatitis is
responsible for transcription of the fgl2 prothrombinase gene. These studies
provide new insights into the role of the nucleocapsid gene in the pathogenesis
of viral hepatitis.
PMID- 10187769
TI - Dynamic epigenetic regulation of initial O-glycosylation by UDP-N
Acetylgalactosamine:Peptide N-acetylgalactosaminyltransferases. site-specific
glycosylation of MUC1 repeat peptide influences the substrate qualities at
adjacent or distant Ser/Thr positions.
AB - In search of possible epigenetic regulatory mechanisms ruling the initiation of O
glycosylation by polypeptide:N-acetylgalactosaminyltransferases, we studied the
influences of mono- and disaccharide substituents of glycopeptide substrates on
the site-specific in vitro addition of N-acetylgalactosamine (GalNAc) residues by
recombinant GalNAc-Ts (rGalNAc-T1, -T2, and -T3). The substrates were 20-mers
(HGV20) or 21-mers (AHG21) of the MUC1 tandem repeat peptide carrying GalNAcalpha
or Galbeta1-3GalNAcalpha at different positions. The enzymatic products were
analyzed by MALDI mass spectrometry and Edman degradation for the number and
sites of incorporated GalNAc. Disaccharide placed on the first position of the
diad Ser-16-Thr-17 prevents glycosylation of the second, whereas disaccharide on
the second position of Ser-16-Thr-17 and Thr-5-Ser-6 does not prevent GalNAc
addition to the first. Multiple disaccharide substituents suppress any further
glycosylation at the remaining sites. Glycosylation of Ser-16 is negatively
affected by glycosylation at position -6 (Thr-10) or -10 (Ser-6) and is inhibited
by disaccharide at position -11 (Thr-5), suggesting the occurrence of
glycosylation-induced effects on distant acceptor sites. Kinetic studies revealed
the accelerated addition of GalNAc to Ser-16 adjacent to GalNAc-substituted Thr
17, demonstrating positive regulatory effects induced by glycosylation on the
monosaccharide level. These antagonistic effects of mono- and disaccharides could
underlie a postulated regulatory mechanism.
PMID- 10187770
TI - CIPER, a novel NF kappaB-activating protein containing a caspase recruitment
domain with homology to Herpesvirus-2 protein E10.
AB - We have identified and characterized CIPER, a novel protein containing a caspase
recruitment domain (CARD) in its N terminus and a C-terminal region rich in
serine and threonine residues. The CARD of CIPER showed striking similarity to
E10, a product of the equine herpesvirus-2. CIPER formed homodimers via its CARD
and interacted with viral E10 but not with several apoptosis regulators
containing CARDs including ARC, RAIDD, RICK, caspase-2, caspase-9, or Apaf-1.
Expression of CIPER induced NF-kappaB activation, which was inhibited by dominant
negative NIK and a nonphosphorylable IkappaB-alpha mutant but not by dominant
negative RIP. Mutational analysis revealed that the N-terminal region of CIPER
containing the CARD was sufficient and necessary for NF-kappaB-inducing activity.
Point mutations in highly conserved residues in the CARD of CIPER disrupted the
ability of CIPER to activate NF-kappaB and to form homodimers, indicating that
the CARD is essential for NF-kappaB activation and dimerization. We propose that
CIPER acts in a NIK-dependent pathway of NF-kappaB activation.
PMID- 10187771
TI - Equine herpesvirus-2 E10 gene product, but not its cellular homologue, activates
NF-kappaB transcription factor and c-Jun N-terminal kinase.
AB - We have previously reported on the death effector domain containing E8 gene
product from equine herpesvirus-2, designated FLICE inhibitory protein (v-FLIP),
and on its cellular homologue, c-FLIP, which inhibit the activation of caspase-8
by death receptors. Here we report on the structure and function of the E10 gene
product of equine herpesvirus-2, designated v-CARMEN, and on its cellular
homologue, c-CARMEN, which contain a caspase-recruiting domain (CARD) motif. c
CARMEN is highly homologous to the viral protein in its N-terminal CARD motif but
differs in its C-terminal extension. v-CARMEN and c-CARMEN interact directly in a
CARD-dependent manner yet reveal different binding specificities toward members
of the tumor necrosis factor receptor-associated factor (TRAF) family. v-CARMEN
binds to TRAF6 and weakly to TRAF3 and, upon overexpression, potently induces the
c-Jun N-terminal kinase (JNK), p38, and nuclear factor (NF)-kappaB
transcriptional pathways. c-CARMEN or truncated versions thereof do not appear to
induce JNK and NF-kappaB activation by themselves, nor do they affect the JNK and
NF-kappaB activating potential of v-CARMEN. Thus, in contrast to the cellular
homologue, v-CARMEN may have additional properties in its unique C terminus that
allow for an autonomous activator effect on NF-kappaB and JNK. Through activation
of NF-kappaB, v-CARMEN may regulate the expression of the cellular and viral
genes important for viral replication.
PMID- 10187772
TI - Transcriptional regulation of the Schizosaccharomyces pombe malic enzyme gene,
mae2.
AB - The NAD-dependent malic enzyme from Schizosaccharomyces pombe catalyzes the
oxidative decarboxylation of L-malate to pyruvate and CO2. Transcription of the
S. pombe malic enzyme gene, mae2, was studied to elucidate the regulatory
mechanisms involved in the expression of the gene. No evidence for substrate
induced expression of mae2 was observed in the presence of 0.2% L-malate.
However, transcription of mae2 was induced when cells were grown in high
concentrations of glucose or under anaerobic conditions. The increased levels of
malic enzyme may provide additional pyruvate or assist in maintaining the redox
potential under fermentative conditions. Deletion and mutation analyses of the 5'
flanking region of the mae2 gene revealed the presence of three novel negative
cis-acting elements, URS1, URS2, and URS3, that seem to function cooperatively to
repress transcription of the mae2 gene. URS1 and URS2 are also present in the
promoter region of the S. pombe malate transporter gene, suggesting co-regulation
of their expression. Furthermore, two positive cis-acting elements in the mae2
promoter, UAS1 and UAS2, show homology with the DNA recognition sites of the cAMP
dependent transcription factors ADR1, AP-2, and ATF (activating transcription
factor)/CREB (cAMP response element binding).
PMID- 10187773
TI - Molecular cloning and expression of a stress-responsive mitogen-activated protein
kinase-related kinase from Tetrahymena cells.
AB - To identify genes responsive to cold stress, we employed the differential display
mRNA analysis technique to isolate a novel gene from Tetrahymena thermophila
which encodes a protein kinase of 430 amino acids. A homolog of this kinase with
90% amino acid sequence identity was also found in T. pyriformis. Both kinases
contain 11 subdomains typical of protein kinases. Sequence analysis revealed that
the predicted amino acid sequences resemble those of mitogen-activated protein
kinase (MAPK), especially p38 and stress-activated protein kinase which are known
to be involved in various stress responses. However, it should be noted that the
tyrosine residue in the normally conserved MAPK phosphorylation site (Thr-X-Tyr)
is replaced by histidine (Thr226-Gly-His228) in this MAPK-related kinase (MRK).
The recombinant MRK expressed in Escherichia coli phosphorylated myelin basic
protein (MBP) and became autophosphorylated. However, the mutated recombinant
protein in which Thr226 was replaced by Ala lost the ability to phosphorylate
MBP, suggesting that Thr226 residue is essential for kinase activity. The MRK
mRNA transcript in T. thermophila increased markedly upon temperature downshift
from 35 to 15 degrees C (0.8 degrees C/min). Interestingly, osmotic shock either
by sorbitol (100-200 mM) or NaCl (25-100 mM) also induced mRNA expression of the
MRK in T. pyriformis. In addition, the activity of the kinase as determined by an
immune complex kinase assay using MBP as a substrate was also induced by osmotic
stress. This is the first demonstration of a MAPK-related kinase in the
unicellular eukaryotic protozoan Tetrahymena that is induced by physical stresses
such as cold temperature and osmolarity. The present results suggest that this
MRK may function in the stress-signaling pathway in Tetrahymena cells.
PMID- 10187774
TI - Assignment of transforming growth factor beta1 and beta3 and a third new ligand
to the type I receptor ALK-1.
AB - Germ line mutations in one of two distinct genes, endoglin or ALK-1, cause
hereditary hemorrhagic telangiectasia (HHT), an autosomal dominant disorder of
localized angiodysplasia. Both genes encode endothelial cell receptors for the
transforming growth factor beta (TGF-beta) ligand superfamily. Endoglin has
homology to the type III receptor, betaglycan, although its exact role in TGF
beta signaling is unclear. Activin receptor-like kinase 1 (ALK-1) has homology to
the type I receptor family, but its ligand and corresponding type II receptor are
unknown. In order to identify the ligand and type II receptor for ALK-1 and to
investigate the role of endoglin in ALK-1 signaling, we devised a chimeric
receptor signaling assay by exchanging the kinase domain of ALK-1 with either the
TGF-beta type I receptor or the activin type IB receptor, both of which can
activate an inducible PAI-1 promoter. We show that TGF-beta1 and TGF-beta3, as
well as a third unknown ligand present in serum, can activate chimeric ALK-1. HHT
associated missense mutations in the ALK-1 extracellular domain abrogate
signaling. The ALK-1/ligand interaction is mediated by the type II TGF-beta
receptor for TGF-beta and most likely through the activin type II or type IIB
receptors for the serum ligand. Endoglin is a bifunctional receptor partner since
it can bind to ALK-1 as well as to type I TGF-beta receptor. These data suggest
that HHT pathogenesis involves disruption of a complex network of positive and
negative angiogenic factors, involving TGF-beta, a new unknown ligand, and their
corresponding receptors.
PMID- 10187775
TI - The cysteine-proximal aspartates in the Fx-binding niche of photosystem I. Effect
of alanine and lysine replacements on photoautotrophic growth, electron transfer
rates, single-turnover flash efficiency, and EPR spectral properties.
AB - The FX electron acceptor in Photosystem I (PS I) is a highly electronegative (Em
= -705 mV) interpolypeptide [4Fe-4S] cluster ligated by cysteines 556 and 565 on
PsaB and cysteines 574 and 583 on PsaA in Synechocystis sp. PCC 6803. An aspartic
acid is adjacent to each of these cysteines on PsaB and adjacent to the proline
proximal cysteine on PsaA. We investigated the effect of D566PsaB and D557PsaB on
electron transfer through FX by changing each aspartate to the neutral alanine or
to the positively charged lysine either singly (D566APsaB, D557APsaB, D566KPsaB,
and D557KPsaB) or in pairs (D557APsaB/D566APsaB and D557KPsaB/D566APsaB). All
mutants except for D557KPsaB/D566APsaB grew photoautotrophically, but the growth
of D557KPsaB and D557APsaB/D566APsaB was impaired under low light. The doubling
time was increased, and the chlorophyll content per cell was lower in D557KPsaB
and D557APsaB/D566APsaB relative to the wild type and the other mutants.
Nevertheless, the rates of NADP+ photoreduction in PS I complexes from all
mutants were no less than 75% of that of the wild type. The kinetics of back
reaction of the electron acceptors on a single-turnover flash showed efficient
electron transfer to the terminal acceptors FA and FB in PS I complexes from all
mutants. The EPR spectrum of FX was identical to that in the wild type in all but
the single and double D566APsaB mutants, where the high-field resonance was
shifted downfield. We conclude that the impaired growth of some of the mutants is
related to a reduced accumulation of PS I rather than to photosynthetic
efficiency. The chemical nature and the charge of the amino acids adjacent to the
cysteine ligands on PsaB do not appear to be significant factors in the
efficiency of electron transfer through FX.
PMID- 10187777
TI - Ligand binding to the amino-terminal domain of the mGluR4 subtype of metabotropic
glutamate receptor.
AB - The metabotropic glutamate receptor (mGluR) 4 subtype of metabotropic glutamate
receptor is a presynaptic receptor that modulates neurotransmitter release. We
have characterized the properties of a truncated, epitope-tagged construct
containing part of the extracellular amino-terminal domain of mGluR4. The
truncated receptor was secreted into the cell culture medium of transfected human
embryonic kidney cells. The oligomeric structure of the soluble truncated
receptor was assessed by gel electrophoresis. In the presence of high
concentrations of a reducing agent, the truncated receptor migrated as a monomer;
at lower concentrations of the reducing agent, only higher molecular weight
oligomers were observed. Competition binding experiments using the radiolabeled
agonist [3H]L-2-amino-4-phosphonobutyric acid revealed that the rank order of
potency of metabotropic ligands at the truncated receptor was similar to that of
the full-length membrane-bound receptor. However, the truncated receptor
displayed higher affinities for agonists and lower affinities for antagonists
compared with the full-length receptor. Deglycosylation produced a shift in the
relative molecular weight of the soluble protein from Mr = 71,000 to Mr = 63,000;
deglycosylation had no effect on the binding of [3H]L-2-amino-4-phosphonobutyric
acid, indicating that the asparagine-linked carbohydrates are not necessary for
agonist binding. These results demonstrate that although the primary determinants
of ligand binding to mGluR4 are contained within the first 548 amino acids of the
receptor, additional amino acids located downstream of this region may influence
the affinity of ligands for the binding site.
PMID- 10187776
TI - The role of phosphatidylinositol 3-kinase in vascular endothelial growth factor
signaling.
AB - Vascular endothelial growth factor (VEGF) receptor Flk-1/KDR in endothelial cells
is activated during vasculogenesis and angiogenesis upon ligand-receptor
interaction. Activated Flk-1/KDR has been shown to recruit Src homology 2 domain
containing signaling molecules that are known to serve as links to the activation
of the mitogen-activated protein (MAP) kinase signaling pathway. To define the
functional significance of phosphatidylinositol (PI) 3-kinase in VEGF signaling,
we have examined its role in human umbilical vein endothelial cell (HUVEC) cycle
progression. We show herein that p85, the regulatory subunit of PI 3-kinase, is
constitutively associated with Flk-1/KDR. The treatment of HUVECs with VEGF
promoted tyrosine autophosphorylation of Flk-1/KDR and also induced
phosphorylation of p85. This was followed by an increase in the PI 3-kinase
activity, which was sensitive to wortmannin, a potent PI 3-kinase inhibitor. VEGF
also induced a striking activation of MAP kinase in a time-dependent manner.
Inhibition studies with both a dominant-negative p85 mutant and the PI 3-kinase
inhibitor, wortmannin, were employed to show for the first time that VEGF
stimulated PI 3-kinase modulates MAP kinase activation and nuclear events such as
transcription from c-fos promoter and entry into the synthesis (S)-phase. Our
data demonstrate the importance of PI 3-kinase as a necessary signaling component
of VEGF-mediated cell cycle progression.
PMID- 10187778
TI - Structural basis for the resistance of Tay-Sachs ganglioside GM2 to enzymatic
degradation.
AB - To understand the reason why, in the absence of GM2 activator protein, the GalNAc
and the NeuAc in GM2 (GalNAcbeta1-->4(NeuAcalpha2-->3)Galbeta1-->4Glcbet a1
1'Cer) are refractory to beta-hexosaminidase A and sialidase, respectively, we
have recently synthesized a linkage analogue of GM2 named 6'GM2 (GalNAcbeta1-
>6(NeuAcalpha2-->3)Galbeta1-->4Glcbet a1-1'Cer). While GM2 has GalNAcbeta1-->4Gal
linkage, 6'-GM2 has GalNAcbeta1-->6Gal linkage (Ishida, H., Ito, Y., Tanahashi,
E., Li, Y.-T., Kiso, M., and Hasegawa, A. (1997) Carbohydr. Res. 302, 223-227).
We have studied the enzymatic susceptibilities of GM2 and 6'GM2, as well as that
of the oligosaccharides derived from GM2, asialo-GM2 (GalNAcbeta1-->4Galbeta1-->
4Glcbeta1-1'Cer) and 6'GM2. In addition, the conformational properties of both
GM2 and 6'GM2 were analyzed using NMR spectroscopy and molecular mechanics
computation. In sharp contrast to GM2, the GalNAc and the Neu5Ac of 6'GM2 were
readily hydrolyzed by beta-hexosaminidase A and sialidase, respectively, without
GM2 activator. Among the oligosaccharides derived from GM2, asialo-GM2, and
6'GM2, only the oligosaccharide from GM2 was resistant to beta-hexosaminidase A.
Conformational analyses revealed that while GM2 has a compact and rigid
oligosaccharide head group, 6'GM2 has an open spatial arrangement of the sugar
units, with the GalNAc and the Neu5Ac freely accessible to external interactions.
These results strongly indicate that the resistance of GM2 to enzymatic
hydrolysis is because of the specific rigid conformation of the GM2
oligosaccharide.
PMID- 10187779
TI - Macrophage metalloelastase, MMP-12, cleaves human apolipoprotein(a) in the linker
region between kringles IV-4 and IV-5. Potential relevance to lipoprotein(a)
biology.
AB - In this study we found that macrophage metalloelastase, MMP-12 cleaves, in vitro,
apolipoprotein(a) (apo(a)) in the Asn3518-Val3519 bond located in the linker
region between kringles IV-4 and IV-5, a bond immediately upstream of the Ile3520
Leu3521 bond, shown previously to be the site of action by neutrophil elastase
(NE). We have also shown that human apo(a) injected into the tail vein of control
mice undergoes degradation as reflected by the appearance of immunoreactive
fragments in the plasma and in the urine of these animals. To define whether
either or both of these enzymes may be responsible for the in vivo apo(a)
cleavage, we injected intravenously MMP-12(-/-), NE -/- mice and litter mates,
all of the same strain, with either lipoprotein(a) (Lp(a)), full-length free
apo(a), or its N-terminal fragment, F1, obtained by the in vitro cleavage of
apo(a) by NE. In the plasma of Lp(a)/apo(a)-injected mice, F1 was detected in
control and NE -/- mice but was virtually absent in the MMP-12(-/-) mice.
Moreover, fragments of the F1 type were present in the urine of the animals
except for the MMP-12(-/-) mice. These fragments were significantly smaller in
size than those observed in the plasma. All of the animals injected with F1
exhibited small sized fragments in their urine. These observations provide
evidence that, in the mouse strain used, MMP-12 plays an important role in the
generation of F1 from injected human Lp(a)/apo(a) and that this fragment
undergoes further cleavage during renal transit via a mechanism that is neither
NE- nor MMP-12-dependent. Thus, factors influencing the expression of MMP-12 may
have a modulating action on the biology of Lp(a).
PMID- 10187780
TI - Constitutive activation of the prolactin receptor results in the induction of
growth factor-independent proliferation and constitutive activation of signaling
molecules.
AB - The ability to induce the oncogenic activation of the human prolactin receptor
(PRLR) was examined by deleting 178 amino acids of the extracellular ligand
binding domain. Expression of this deletion mutant in the interleukin-3 (IL-3)
dependent murine myeloid cell line 32Dcl3 resulted in the induction of growth
factor-independent proliferation. Parental 32Dcl3 cells proliferated only in the
presence of exogenous murine IL-3 (mIL-3), while 32Dcl3 cells transfected with
the long form of the human PRLR were able to proliferate in response to mIL-3,
ovine prolactin, or human PRL. Cells expressing the Delta178 deletion mutant
contained numerous phosphotyrosine-containing proteins in the absence of
stimulation with either mIL-3 or ovine prolactin. Growth factor stimulation
increased the number of proteins phosphorylated and the intensity of
phosphorylation. These proteins included constitutively phosphorylated Janus
kinase 2, signal transducer and activator of transcription 5, and SHC. Activated
extracellular signal-regulated kinases 1 and 2 (ERK1 and ERK2) were observed in
unstimulated 32Dcl3 cells expressing the Delta178 mutant. Likewise, transfection
of Nb2 cells with the Delta178 deletion mutant induced growth factor-independent
proliferation and constitutive activation of Janus kinase 2, ERK1, and ERK2. In
addition to the induction of a growth factor-independent state, the expression of
the Delta178 deletion mutant also suppressed the apoptosis that occurs when
32Dcl3 cells are cultured in the absence of growth factors such as IL-3. These
data suggest that the constitutive activation of the PRLR can be achieved by
deletion of the ligand binding domain and that this mutation leads to the
oncogenic activation of the receptor as determined by the ability of the receptor
to induce growth factor-independent proliferation of factor-dependent
hematopoietic cells.
PMID- 10187782
TI - Cyanobacterial PPP family protein phosphatases possess multifunctional
capabilities and are resistant to microcystin-LR.
AB - The structural gene for a putative PPP family protein-serine/threonine
phosphatase from the microcystin-producing cyanobacterium Microcystis aeruginosa
PCC 7820, pp1-cyano1, was cloned. The sequence of the predicted gene product, PP1
cyano1, was 98% identical to that of the predicted product of an open reading
frame, pp1-cyano2, from a cyanobacterium that does not produce microcystins, M.
aeruginosa UTEX 2063. By contrast, PP1-cyano1 displayed less than 20% identity
with other PPP family protein phosphatases from eukaryotic, archaeal, or other
bacterial organisms. PP1-cyano1 and PP1-cyano2 were expressed in Escherichia coli
and purified to homogeneity. Both enzymes exhibited divalent metal dependent
phosphohydrolase activity in vitro toward phosphoserine- and phosphotyrosine
containing proteins and 3-phosphohistidine- and phospholysine-containing amino
acid homopolymers. This multifunctional potential also was apparent in samples of
PP1-cyano1 and PP1-cyano2 isolated from M. aeruginosa. Catalytic activity was
insensitive to okadaic acid or the cyanobacterially produced cyclic heptapeptide,
microcystin-LR, both potent inhibitors of mammalian PP1 and PP2A. PP1-cyano1 and
PP1-cyano2 displayed diadenosine tetraphosphatase activity in vitro. Diadenosine
tetraphosphatases share conserved sequence features with PPP family protein
phosphatases. The diadenosine tetraphosphatase activity of PP1-cyano1 and PP1
cyano2 confirms that these enzymes share a common catalytic mechanism.
PMID- 10187781
TI - Inhibition of phospholipase A2-mediated arachidonic acid release by cyclic AMP
defines a negative feedback loop for P2Y receptor activation in Madin-Darby
canine kidney D1 cells.
AB - In Madin-Darby canine kidney D1 cells extracellular nucleotides activate P2Y
receptors that couple to several signal transduction pathways, including
stimulation of multiple phospholipases and adenylyl cyclase. For one class of P2Y
receptors, P2Y2 receptors, this stimulation of adenylyl cyclase and increase in
cAMP occurs via the conversion of phospholipase A2 (PLA2)-generated arachidonic
acid (AA) to prostaglandins (e.g. PGE2). These prostaglandins then stimulate
adenylyl cyclase activity, presumably via activation of prostanoid receptors. In
the current study we show that agents that increase cellular cAMP levels
(including PGE2, forskolin, and the beta-adrenergic agonist isoproterenol) can
inhibit P2Y receptor-promoted AA release. The protein kinase A (PKA) inhibitor
H89 blocks this effect, suggesting that this feedback inhibition occurs via
activation of PKA. Studies with PGE2 indicate that inhibition of AA release is
attributable to inhibition of mitogen-activated protein kinase activity and in
turn of P2Y receptor stimulated PLA2 activity. Although cAMP/PKA-mediated
inhibition occurs for P2Y receptor-promoted AA release, we did not find such
inhibition for epinephrine (alpha1-adrenergic) or bradykinin-mediated AA release.
Taken together, these results indicate that negative feedback regulation via
cAMP/PKA-mediated inhibition of mitogen-activated protein kinase occurs for some,
but not all, classes of receptors that promote PLA2 activation and AA release. We
speculate that receptor-selective feedback inhibition occurs because PLA2
activation by different receptors in Madin-Darby canine kidney D1 cells involves
the utilization of different signaling components that are differentially
sensitive to increases in cAMP or, alternatively, because of compartmentation of
signaling components.
PMID- 10187783
TI - NSP1 defines a novel family of adaptor proteins linking integrin and tyrosine
kinase receptors to the c-Jun N-terminal kinase/stress-activated protein kinase
signaling pathway.
AB - As part of a program to further understand the mechanism by which extracellular
signals are coordinated and cell-specific outcomes are generated, we have cloned
a novel class of related adaptor molecules (NSP1, NSP2, and NSP3) and have
characterized in more detail one of the members, NSP1. NSP1 has an Shc-related
SH2 domain and a putative proline/serine-rich SH3 interaction domain. Treatment
of cells with epidermal growth factor or insulin leads to NSP1 phosphorylation
and increased association with a hypophosphorylated adaptor protein, p130(Cas).
In contrast, cell contact with fibronectin results in Cas phosphorylation and a
transient dissociation of NSP1 from p130(Cas). Increased expression of NSP1 in
293 cells induces activation of JNK1, but not of ERK2. Consistent with this
observation, NSP1 increases the activity of an AP-1-containing promoter. Thus, we
have described a novel family of adaptor proteins, one of which may be involved
in the process by which receptor tyrosine kinase and integrin receptors control
the c-Jun N-terminal kinase/stress-activated protein kinase pathway.
PMID- 10187784
TI - Molecular uncoupling of fractalkine-mediated cell adhesion and signal
transduction. Rapid flow arrest of CX3CR1-expressing cells is independent of G
protein activation.
AB - Fractalkine is a novel multidomain protein expressed on the surface of activated
endothelial cells. Cells expressing the chemokine receptor CX3CR1 adhere to
fractalkine with high affinity, but it is not known if adherence requires G
protein activation and signal transduction. To investigate the cell adhesion
properties of fractalkine, we created mutated forms of CX3CR1 that have little or
no ability to transduce intracellular signals. Cells expressing signaling
incompetent forms of CX3CR1 bound rapidly and with high affinity to immobilized
fractalkine in both static and flow assays. Video microscopy revealed that CX3CR1
expressing cells bound more rapidly to fractalkine than to VCAM-1 (60 versus 190
ms). Unlike VCAM-1, fractalkine did not mediate cell rolling, and after capture
on fractalkine, cells did not dislodge. Finally, soluble fractalkine induced
intracellular calcium fluxes and chemotaxis, but it did not activate integrins.
Taken together these data provide strong evidence that CX3CR1, a seven
transmembrane domain receptor, mediates robust cell adhesion to fractalkine in
the absence of G-protein activation and suggest a novel role for this receptor as
an adhesion molecule.
PMID- 10187785
TI - Conformational change in the human glucocorticoid receptor induced by ligand
binding is altered by mutation of isoleucine 747 by a threonine.
AB - Limited proteolysis experiments were performed to study conformation changes
induced by ligand binding on in vitro produced wild-type and I747T mutant
glucocorticoid receptors. Dexamethasone-induced conformational changes were
characterized by two resistant proteolysis fragments of 30 and 27 kDa. Although
dexamethasone binding affinity was only slightly altered by the I747T
substitution (Roux, S., Terouanne, B., Balaguer, P., Loffreda-Jausons, N., Pons,
M., Chambon, P., Gronemeyer, H., and Nicolas, J.-C. (1996) Mol. Endocrinol. 10,
1214-1226), higher dexamethasone concentrations were required to obtain the same
proteolysis pattern. This difference was less marked when proteolysis experiments
were conducted at 0 degrees C, indicating that a step of the conformational
change after ligand binding was affected by the mutation. In contrast, RU486
binding to the wild-type receptor induced a different conformational change that
was not affected by the mutation. Analysis of proteolysis fragments obtained in
the presence of dexamethasone or RU486 indicated that the RU486-induced
conformational change affected the C-terminal part of the ligand binding domain
differently. These data suggest that the ligand-induced conformational change
occurs via a multistep process. In the first step, characterized by compaction of
the ligand binding domain, the mutation has no effect. The second step, which
stabilizes the activated conformation and does not occur at 4 degrees C, seems to
be a key element in the activation process that can be altered by the mutation.
This step could involve modification of the helix H12 position, explaining why
the conformation induced by RU486 is not affected by the mutation.
PMID- 10187786
TI - A post-transcriptional compensatory pathway in heterozygous ventricular myosin
light chain 2-deficient mice results in lack of gene dosage effect during normal
cardiac growth or hypertrophy.
AB - Our previous study of homozygous mutants of the ventricular specific isoform of
myosin light chain 2 (mlc-2v) demonstrated that mlc-2v plays an essential role in
murine heart development (Chen, J., Kubalak, S. W., Minamisawa, S., Price, R. L.,
Becker, K. D., Hickey, R., Ross, J., Jr., and Chien, K. R. (1998) J. Biol. Chem.
273, 1252-1256). As gene dosage of some myofibrillar proteins can affect muscle
function, we have analyzed heterozygous mutants in depth. Ventricles of
heterozygous mutants displayed a 50% reduction in mlc-2v mRNA, yet expressed
normal levels of protein both under basal conditions and following induction of
cardiac hypertrophy by aortic constriction. Heterozygous mutants exhibited
cardiac function comparable to that of wild-type littermate controls both prior
to and following aortic constriction. There were no significant differences in
contractility and responses to calcium between wild-type and heterozygous
unloaded cardiomyocytes. We conclude that heterozygous mutants show neither a
molecular nor a physiological cardiac phenotype either at base line or following
hypertrophic stimuli. These results suggest that post-transcriptional
compensatory mechanisms play a major role in maintaining the level of MLC-2v
protein in murine hearts. In addition, as our mlc-2v knockout mutants were
created by a knock-in of Cre recombinase into the endogenous mlc-2v locus, this
study demonstrates that heterozygous mlc-2v cre knock-in mice are appropriate for
ventricular specific gene targeting.
PMID- 10187787
TI - An inhibitor of p38 mitogen-activated protein kinase prevents insulin-stimulated
glucose transport but not glucose transporter translocation in 3T3-L1 adipocytes
and L6 myotubes.
AB - The precise mechanisms underlying insulin-stimulated glucose transport still
require investigation. Here we assessed the effect of SB203580, an inhibitor of
the p38 MAP kinase family, on insulin-stimulated glucose transport in 3T3-L1
adipocytes and L6 myotubes. We found that SB203580, but not its inactive analogue
(SB202474), prevented insulin-stimulated glucose transport in both cell types
with an IC50 similar to that for inhibition of p38 MAP kinase (0.6 microM). Basal
glucose uptake was not affected. Moreover, SB203580 added only during the
transport assay did not inhibit basal or insulin-stimulated transport. SB203580
did not inhibit insulin-stimulated translocation of the glucose transporters
GLUT1 or GLUT4 in 3T3-L1 adipocytes as assessed by immunoblotting of subcellular
fractions or by immunofluorescence of membrane lawns. L6 muscle cells expressing
GLUT4 tagged on an extracellular domain with a Myc epitope (GLUT4myc) were used
to assess the functional insertion of GLUT4 into the plasma membrane. SB203580
did not affect the insulin-induced gain in GLUT4myc exposure at the cell surface
but largely reduced the stimulation of glucose uptake. SB203580 had no effect on
insulin-dependent insulin receptor substrate-1 phosphorylation, association of
the p85 subunit of phosphatidylinositol 3-kinase with insulin receptor substrate
1, nor on phosphatidylinositol 3-kinase, Akt1, Akt2, or Akt3 activities in 3T3-L1
adipocytes. In conclusion, in the presence of SB203580, insulin caused normal
translocation and cell surface membrane insertion of glucose transporters without
stimulating glucose transport. We propose that insulin stimulates two independent
signals contributing to stimulation of glucose transport: phosphatidylinositol 3
kinase leads to glucose transporter translocation and a pathway involving p38 MAP
kinase leads to activation of the recruited glucose transporter at the membrane.
PMID- 10187788
TI - Translational enhancement by an element downstream of the initiation codon in
Escherichia coli.
AB - The translation initiation of Escherichia coli mRNAs is known to be facilitated
by a cis element upstream of the initiation codon, called the Shine-Dalgarno (SD)
sequence. This sequence complementary to the 3' end of 16 S rRNA enhances the
formation of the translation initiation complex of the 30 S ribosomal subunit
with mRNAs. It has been debated that a cis element called the downstream box
downstream of the initiation codon, in addition to the SD sequence, facilitates
formation of the translation initiation complex; however, conclusive evidence
remains elusive. Here, we show evidence that the downstream box plays a major
role in the enhancement of translation initiation in concert with SD.
PMID- 10187789
TI - Inhibition of the Ca2+/calmodulin-dependent protein kinase I cascade by cAMP
dependent protein kinase.
AB - Several recent studies have shown that Ca2+/calmodulin-dependent protein kinase I
(CaMKI) is phosphorylated and activated by a protein kinase (CaMKK) that is
itself subject to regulation by Ca2+/calmodulin. In the present study, we
demonstrate that this enzyme cascade is regulated by cAMP-mediated activation of
cAMP-dependent protein kinase (PKA). In vitro, CaMKK is phosphorylated by PKA and
this is associated with inhibition of enzyme activity. The major site of
phosphorylation is threonine 108, although additional sites are phosphorylated
with lower efficiency. In vitro, CaMKK is also phosphorylated by CaMKI at the
same sites as PKA, suggesting that this regulatory phosphorylation might play a
role as a negative-feedback mechanism. In intact PC12 cells, activation of PKA
with forskolin resulted in a rapid inhibition of both CaMKK and CaMKI activity.
In hippocampal slices CaMKK was phosphorylated under basal conditions, and
activation of PKA led to an increase in phosphorylation. Two-dimensional
phosphopeptide mapping indicated that activation of PKA led to increased
phosphorylation of multiple sites including threonine 108. These results indicate
that in vitro and in intact cells the CaMKK/CaMKI cascade is subject to
inhibition by PKA-mediated phosphorylation of CaMKK. The phosphorylation and
inhibition of CaMKK by PKA is likely to be involved in modulating the balance
between cAMP- and Ca2+-dependent signal transduction pathways.
PMID- 10187790
TI - Continuous primary sequence requirements in the 18-nucleotide promoter of dicot
plant mitochondria.
AB - The nucleotide requirements of mitochondrial promoters of dicot plants were
studied in detail in a pea in vitro transcription system. Deletions in the 5'
regions of three different transcription initiation sites from pea, soybean, and
Oenothera identified a crucial AT-rich sequence element (AT-Box) comprising
nucleotide positions -14 to -9 relative to the first transcribed nucleotide.
Transversion of the AT-Box sequence to comple- mentary nucleotide identities
results in an almost complete loss of promoter activity, suggesting that primary
structure rather than a simple accumulation of adenines and thymidines in this
region is essential for promoter activity. This promoter segment thus appears to
be involved in sequence specific binding of a respective protein factor(s) rather
than merely loosening and melting the DNA helix during or for an initiation
event. Manipulation of nucleotide identities in the 3' portion of the pea atp9
promoter and the respective 3'-flanking region revealed that essential sequences
extend to positions +3/+4 beyond this transcription start site. Efficient
transcription initiation at an 18-base pair promoter sequence ranging from
nucleotide positions -14 to +4 integrated into different sequence contexts shows
this element to be sufficient for autonomous promoter function independent of
surrounding sequences.
PMID- 10187791
TI - Stoichiometry of a ligand-gated ion channel determined by fluorescence energy
transfer.
AB - We have developed a method to determine the stoichiometry of subunits within an
oligomeric cell surface receptor using fluorescently tagged antibodies to the
individual subunits and measuring energy transfer between them. Anti-c-Myc
monoclonal antibody (mAb 9-E10) derivatized with a fluorophore (europium
cryptate, EuK) was used to individually label c-Myc-tagged alpha1-, beta2-, or
gamma2-subunits of the hetero-oligomeric gamma-aminobutyric acid (GABAA) receptor
in intact cells. The maximal fluorescent signal derived from the alpha1(c
Myc)beta2gamma2 and the alpha1beta2(c-Myc)gamma2 receptors was twice that
obtained with alpha1beta2gamma2(c-Myc), suggesting that there are 2x alpha-, 2x
beta-, and 1x gamma-subunits in a receptor monomer. This observation was extended
using fluorescence energy transfer. Receptors were half-maximally saturated with
EuK-anti-c-Myc mAb, and the remaining alpha1(c-Myc) subunits were labeled with
excess anti-c-Myc mAb derivatized with the fluorescence energy acceptor, XL665.
On exposure to laser light, energy transfer from EuK to XL665 occurred with
alpha1(c-Myc)beta2gamma2 and alpha1beta2(c-Myc)gamma2, but no significant energy
transfer was observed with alpha1beta2gamma2(c-Myc) receptors, indicating the
absence of a second gamma-subunit in a receptor monomer. We confirm that the
GABAA receptor subtype, alpha1beta2gamma2, is composed of two copies each of the
alpha- and beta-subunits and one copy of the gamma-subunit (i.e.
(alpha1)2(beta2)2(gamma2)1) and conclude that this method would have general
applicability to other multisubunit cell surface proteins.
PMID- 10187792
TI - DNA methyltransferase is a downstream effector of cellular transformation
triggered by simian virus 40 large T antigen.
AB - This paper tests the hypothesis that DNA methyltransferase plays a causal role in
cellular transformation induced by SV40 T antigen. We show that T antigen
expression results in elevation of DNA methyltransferase (MeTase) mRNA, DNA
MeTase protein levels, and global genomic DNA methylation. A T antigen mutant
that has lost the ability to bind pRb does not induce DNA MeTase. This up
regulation of DNA MeTase by T antigen occurs mainly at the posttranscriptional
level by altering mRNA stability. Inhibition of DNA MeTase by antisense
oligonucleotide inhibitors results in inhibition of induction of cellular
transformation by T antigen as determined by a transient transfection and soft
agar assay. These results suggest that elevation of DNA MeTase is an essential
component of the oncogenic program induced by T antigen.
PMID- 10187793
TI - Long QT syndrome-associated mutations in the Per-Arnt-Sim (PAS) domain of HERG
potassium channels accelerate channel deactivation.
AB - Mutations in the human ether-a-go-go-related gene (HERG) cause long QT syndrome,
an inherited disorder of cardiac repolarization that predisposes affected
individuals to life-threatening arrhythmias. HERG encodes the cardiac rapid
delayed rectifier potassium channel that mediates repolarization of ventricular
action potentials. In this study, we used the oocyte expression system and
voltage clamp techniques to determine the functional consequences of eight long
QT syndrome-associated mutations located in the amino-terminal region of HERG
(F29L, N33T, G53R, R56Q, C66G, H70R, A78P, and L86R). Mutant subunits formed
functional channels with altered gating properties when expressed alone in
oocytes. Deactivation was accelerated by all mutations. Some mutants shifted the
voltage dependence of channel availability to more positive potentials. Voltage
ramps indicated that fast deactivation of mutant channels would reduce outward
current during the repolarization phase of the cardiac action potential and cause
prolongation of the corrected QT interval, QTc. The amino-terminal region of HERG
was recently crystallized and shown to possess a Per-Arnt-Sim (PAS) domain. The
location of these mutations suggests they may disrupt the PAS domain and
interfere with its interaction with the S4-S5 linker of the HERG channel.
PMID- 10187794
TI - The identification of primary sites of superoxide and hydrogen peroxide formation
in the aerobic respiratory chain and sulfite reductase complex of Escherichia
coli.
AB - The fitness of organisms depends upon the rate at which they generate superoxide
(O-2) and hydrogen peroxide (H2O2) as toxic by-products of aerobic metabolism. In
Escherichia coli these oxidants arise primarily from the autoxidation of
components of its respiratory chain. Inverted vesicles that were incubated with
NADH generated O-2 and H2O2 at accelerated rates either when treated with cyanide
or when devoid of quinones, implicating an NADH dehydrogenase as their source.
Null mutations in the gene encoding NADH dehydrogenase II averted autoxidation of
vesicles, and its overproduction accelerated it. Thus NADH dehydrogenase II but
not NADH dehydrogenase I, respiratory quinones, or cytochrome oxidases formed
substantial O-2 and H2O2. NADH dehydrogenase II that was purified from both wild
type and quinone-deficient cells generated approximately 130 H2O2 and 15 O-2 min
1 by autoxidation of its reduced FAD cofactor. Sulfite reductase is a second
autoxidizable electron transport chain of E. coli, containing FAD, FMN, [4Fe-4S],
and siroheme moieties. Purified flavoprotein that contained only the FAD and FMN
cofactors had about the same oxidation turnover number as did the holoenzyme, 7
min-1 FAD-1. Oxidase activity was largely lost upon FMN removal. Thus the
autoxidation of sulfite reductase, like that of the respiratory chain, occurs
primarily by autoxidation of an exposed flavin cofactor. Great variability in the
oxidation turnover numbers of these and other flavoproteins suggests that
endogenous oxidants will be predominantly formed by only a few oxidizable
enzymes. Thus the degree of oxidative stress in a cell may depend upon the titer
of such enzymes and accordingly may vary with growth conditions and among
different cell types. Furthermore, the chemical nature of these reactions was
manifested by their acceleration at high temperatures and oxygen concentrations.
Thus these environmental parameters may also directly affect the O-2 and H2O2
loads that organisms must bear.
PMID- 10187795
TI - The pre-transmembrane 1 domain of acid-sensing ion channels participates in the
ion pore.
AB - The acid-sensing ion channel (ASIC) subunits ASIC1, ASIC2, and ASIC3 are members
of the amiloride-sensitive Na+ channel/degenerin family of ion channels. They
form proton-gated channels that are expressed in the central nervous system and
in sensory neurons, where they are thought to play an important role in pain
accompanying tissue acidosis. A splice variant of ASIC2, ASIC2b, is not active on
its own but modifies the properties of ASIC3. In particular, whereas most members
of the amiloride-sensitive Na+ channel/degenerin family are highly selective for
Na+ over K+, ASIC3/ASIC2b heteromultimers show a nonselective component. Chimeras
of the two splice variants allowed identification of a 9-amino acid region
preceding the first transmembrane (TM) domain (pre-TM1) of ASIC2 that is involved
in ion permeation and is critical for Na+ selectivity. Three amino acids in this
region (Ile-19, Phe-20, and Thr-25) appear to be particularly important, because
channels mutated at these residues discriminate poorly between Na+ and K+. In
addition, the pH dependences of the activity of the F20S and T25K mutants are
changed as compared with that of wild-type ASIC2. A corresponding ASIC3 mutant
(T26K) also has modified Na+ selectivity. Our results suggest that the pre-TM1
region of ASICs participates in the ion pore.
PMID- 10187796
TI - The biosynthetic gene cluster for the 26-membered ring polyene macrolide
pimaricin. A new polyketide synthase organization encoded by two subclusters
separated by functionalization genes.
AB - The biosynthetic gene cluster for the 26-membered ring of the polyene macrolide
pimaricin extends for about 110 kilobase pairs of contiguous DNA in the genome of
Streptomyces natalensis. Two sets of polyketide synthase (PKS) genes are
separated by a group of small polyketide-functionalizing genes. Two of the
polyketide synthase genes, pimS0 and pimS1, have been fully sequenced and
disrupted proving the involvement of each of these genes in pimaricin
biosynthesis. The pimS0 gene encodes a relatively small acetate-activating PKS
(approximately 193 kDa) that appears to work as a loading protein which
"presents" the starter unit to the second PKS subunit. The pimS1 gene encodes a
giant multienzyme (approximately 710 kDa) harboring 15 activities responsible for
the first four cycles of chain elongation in pimaricin biosynthesis, resulting in
formation of the polyene chromophore.
PMID- 10187797
TI - Activation of p38 mitogen-activated protein kinase by PYK2/related adhesion focal
tyrosine kinase-dependent mechanism.
AB - The stress-activated p38 mitogen-activated protein kinase (p38 MAPK), a member of
the subgroup of mammalian kinases, appears to play an important role in
regulating inflammatory responses, including cytokine secretion and apoptosis.
The upstream mediators that link extracellular signals with the p38 MAPK
signaling pathway are currently unknown. Here we demonstrate that pp125 focal
adhesion kinase-related tyrosine kinase RAFTK (also known as PYK2, CADTK) is
activated specifically by methylmethane sulfonate (MMS) and hyperosmolarity but
not by ultraviolet radiation, ionizing radiation, or cis-platinum. Overexpression
of RAFTK leads to the activation of p38 MAPK. Furthermore, overexpression of a
dominant-negative mutant of RAFTK (RAFTK K-M) inhibits MMS-induced p38 MAPK
activation. MKK3 and MKK6 are known potential constituents of p38 MAPK signaling
pathway, whereas SEK1 and MEK1 are upstream activators of SAPK/JNK and ERK
pathways, respectively. We observe that the dominant-negative mutant of MKK3 but
not of MKK6, SEK1, or MEK1 inhibits RAFTK-induced p38 MAPK activity. Furthermore,
the results demonstrate that treatment of cells with 1, 2-bis(2
aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, tetra(acetoxymethyl)-ester, a
membrane-permeable calcium chelator, inhibits MMS-induced activation of RAFTK and
p38 MAPK. Taken together, these findings indicate that RAFTK represents a stress
sensitive mediator of the p38 MAPK signaling pathway in response to certain
cytotoxic agents.
PMID- 10187798
TI - The ubiquitin-homology protein, DAP-1, associates with tumor necrosis factor
receptor (p60) death domain and induces apoptosis.
AB - The tumor necrosis factor receptor, p60 (TNF-R1), transduces death signals via
the association of its cytoplasmic domain with several intracellular proteins. By
screening a mammalian cDNA library using the yeast two-hybrid cloning technique,
we isolated a ubiquitin-homology protein, DAP-1, which specifically interacts
with the cytoplasmic death domain of TNF-R1. Sequence analysis reveals that DAP-1
shares striking sequence homology with the yeast SMT3 protein that is essential
for the maintenance of chromosome integrity during mitosis (Meluh, P. B., and
Koshland, D. (1995) Mol. Biol. Cell 6, 793-807). DAP-1 is nearly identical to
PIC1, a protein that interacts with the PML tumor suppressor implicated in acute
promyelocytic leukemia (Boddy, M. N., Howe, K., Etkin, L. D., Solomon, E., and
Freemont, P. S. (1996) Oncogene 13, 971-982), and the sentrin protein, which
associates with the Fas death receptor (Okura, T., Gong, L., Kamitani, T., Wada,
T., Okura, I., Wei, C. F., Chang, H. M., and Yeh, E. T. (1996) J. Immunol. 157,
4277-4281). The in vivo interaction between DAP-1 and TNF-R1 was further
confirmed in mammalian cells. In transient transfection assays, overexpression of
DAP-1 suppresses NF-kappaB/Rel activity in 293T cells, a human kidney embryonic
carcinoma cell line. Overexpression of either DAP-1 or sentrin causes apoptosis
of TNF-sensitive L929 fibroblast cell line, as well as TNF-resistant osteosarcoma
cell line, U2OS. Furthermore, the dominant negative Fas-associated death domain
protein (FADD) protein blocks the cell death induced by either DAP-1 or FADD.
Collectively, these observations highly suggest a role for DAP-1 in mediating TNF
induced cell death signaling pathways, presumably through the recruitment of FADD
death effector.
PMID- 10187799
TI - The mouse p97 (CDC48) gene. Genomic structure, definition of transcriptional
regulatory sequences, gene expression, and characterization of a pseudogene.
AB - Here we present the first description of the genomic organization,
transcriptional regulatory sequences, and adult and embryonic gene expression for
the mouse p97(CDC48) AAA ATPase. Clones representing two distinct p97 genes were
isolated in a genomic library screen, one of them likely representing a non
functional processed pseudogene. The coding region of the gene encoding the
functional mRNA is interrupted by 16 introns and encompasses 20.4 kilobase pairs.
Definition of the transcriptional initiation site and sequence analysis showed
that the gene contains a TATA-less, GC-rich promoter region with an initiator
element spanning the transcription start site. Cis-acting elements necessary for
basal transcription activity reside within 410 base pairs of the flanking region
as determined by transient transfection assays. In immunohistological analyses,
p97 was widely expressed in embryos and adults, but protein levels were tightly
controlled in a cell type- and cell differentiation-dependent manner. A
remarkable heterogeneity in p97 immunostaining was found on a cellular level
within a given tissue, and protein amounts in the cytoplasm and nucleus varied
widely, suggesting a highly regulated and intermittent function for p97. This
study provides the basis for a detailed analysis of the complex regulation of p97
and the reagents required for assessing its functional significance using
targeted gene manipulation in the mouse.
PMID- 10187800
TI - Nucleotide exchange in genomic DNA of rat hepatocytes using RNA/DNA
oligonucleotides. Targeted delivery of liposomes and polyethyleneimine to the
asialoglycoprotein receptor.
AB - Chimeric RNA/DNA oligonucleotides have been shown to promote single nucleotide
exchange in genomic DNA. A chimeric molecule was designed to introduce an A to C
nucleotide conversion at the Ser365 position of the rat factor IX gene. The
oligonucleotides were encapsulated in positive, neutral, and negatively charged
liposomes containing galactocerebroside or complexed with lactosylated
polyethyleneimine. The formulations were evaluated for stability and efficiency
in targeting hepatocytes via the asialoglycoprotein receptor. Physical
characterization and electron microscopy revealed that the oligonucleotides were
efficiently encapsulated within the liposomes, with the positive and negative
formulations remaining stable for at least 1 month. Transfection efficiencies in
isolated rat hepatocytes approached 100% with each of the formulations. However,
the negative liposomes and 25-kDa lactosylated polyethyleneimine provided the
most intense nuclear fluorescence with the fluorescein-labeled oligonucleotides.
The lactosylated polyethyleneimine and the three different liposomal formulations
resulted in A to C conversion efficiencies of 19-24%. In addition, lactosylated
polyethyleneimine was also highly effective in transfecting plasmid DNA into
isolated hepatocytes. The results suggest that both the liposomal and
polyethyleneimine formulations are simple to prepare and stable and give
reliable, reproducible results. They provide efficient delivery systems to
hepatocytes for the introduction or repair of genetic mutations by the chimeric
RNA/DNA oligonucleotides.
PMID- 10187801
TI - Phosphorylation and free pool of beta-catenin are regulated by tyrosine kinases
and tyrosine phosphatases during epithelial cell migration.
AB - Cell migration requires precise control, which is altered or lost when tumor
cells become invasive and metastatic. Although the integrity of cell-cell
contacts, such as adherens junctions, is essential for the maintenance of
functional epithelia, they need to be rapidly disassembled during migration. The
transmembrane cell adhesion protein E-cadherin and the cytoplasmic catenins are
molecular elements of these structures. Here we demonstrate that epithelial cell
migration is accompanied by tyrosine phosphorylation of beta-catenin and an
increase of its free cytoplasmic pool. We show further that the protein-tyrosine
phosphatase LAR (leukocyte common antigen related) colocalizes with the cadherin
catenin complex in epithelial cells and associates with beta-catenin and
plakoglobin. Interestingly, ectopic expression of protein-tyrosine phosphatase
(PTP) LAR inhibits epithelial cell migration by preventing phosphorylation and
the increase in the free pool of beta-catenin; moreover, it inhibits tumor
formation in nude mice. These data support a function for PTP LAR in the
regulation of epithelial cell-cell contacts at adherens junctions as well as in
the control of beta-catenin signaling functions. Thus PTP-LAR appears to play an
important role in the maintenance of epithelial integrity, and a loss of its
regulatory function may contribute to malignant progression and metastasis.
PMID- 10187803
TI - Alternative structural state of transferrin. The crystallographic analysis of
iron-loaded but domain-opened ovotransferrin N-lobe.
AB - Transferrins bind Fe3+ very tightly in a closed interdomain cleft by the
coordination of four protein ligands (Asp60, Tyr92, Tyr191, and His250 in
ovotransferrin N-lobe) and of a synergistic anion, physiologically bidentate CO32
. Upon Fe3+ uptake, transferrins undergo a large scale conformational transition:
the apo structure with an opening of the interdomain cleft is transformed into
the closed holo structure, implying initial Fe3+ binding in the open form. To
solve the Fe3+-loaded, domain-opened structure, an ovotransferrin N-lobe crystal
that had been grown as the apo form was soaked with Fe3+-nitrilotriacetate, and
its structure was solved at 2.1 A resolution. The Fe3+-soaked form showed almost
exactly the same overall open structure as the iron-free apo form. The electron
density map unequivocally proved the presence of an iron atom with the
coordination by the two protein ligands of Tyr92-OH and Tyr191-OH. Other Fe3+
coordination sites are occupied by a nitrilotriacetate anion, which is stabilized
through the hydrogen bonds with the peptide NH groups of Ser122, Ala123, and
Gly124 and a side chain group of Thr117. There is, however, no clear interaction
between the nitrilotriacetate anion and the synergistic anion binding site,
Arg121.
PMID- 10187802
TI - Residue 2 of TIMP-1 is a major determinant of affinity and specificity for matrix
metalloproteinases but effects of substitutions do not correlate with those of
the corresponding P1' residue of substrate.
AB - The unregulated activities of matrix metalloproteinases (MMPs) are implicated in
disease processes including arthritis and tumor cell invasion and metastasis. MMP
activities are controlled by four homologous endogenous protein inhibitors,
tissue inhibitors of metalloproteinases (TIMPs), yet different TIMPs show little
specificity for individual MMPs. The large interaction interface in the TIMP
1.MMP-3 complex includes a contiguous region of TIMP-1 around the disulfide bond
between Cys1 and Cys70 that inserts into the active site of MMP-3. The effects of
fifteen different substitutions for threonine 2 of this region reveal that this
residue makes a large contribution to the stability of complexes with MMPs and
has a dominant influence on the specificity for different MMPs. The size, charge,
and hydrophobicity of residue 2 are key factors in the specificity of TIMP.
Threonine 2 of TIMP-1 interacts with the S1' specificity pocket of MMP-3, which
is a key to substrate specificity, but the structural requirements in TIMP-1
residue 2 for MMP binding differ greatly from those for the corresponding residue
of a peptide substrate. These results demonstrate that TIMP variants with
substitutions for Thr2 represent suitable starting points for generating more
targeted TIMPs for investigation and for intervention in MMP-related diseases.
PMID- 10187804
TI - The mixed lineage kinase DLK utilizes MKK7 and not MKK4 as substrate.
AB - Mixed lineage kinases DLK (dual leucine zipper-bearing kinase) and MLK3 have been
proposed to function as mitogen-activated protein kinase kinase kinases in
pathways leading to stress-activated protein kinase/c-Jun NH2-terminal kinase
activation. Differences in primary protein structure place these MLK (mixed
lineage kinase) enzymes in separate subfamilies and suggest that they perform
distinct functional roles. Both DLK and MLK3 associated with, phosphorylated, and
activated MKK7 in vitro. Unlike MLK3, however, DLK did not phosphorylate or
activate recombinant MKK4 in vitro. In confirmatory experiments performed in
vivo, DLK both associated with and activated MKK7. The relative localization of
endogenous DLK, MLK3, MKK4, and MKK7 was determined in cells of the nervous
system. Distinct from MLK3, which was identified in non-neuronal cells, DLK and
MKK7 were detected predominantly in neurons in sections of adult rat cortex by
immunocytochemistry. Subcellular fractionation experiments of cerebral cortex
identified DLK and MKK7 in similar nuclear and extranuclear subcellular
compartments. Concordant with biochemical experiments, however, MKK4 occupied
compartments distinct from that of DLK and MKK7. That DLK and MKK7 occupied
subcellular compartments distinct from MKK4 was confirmed by immunocytochemistry
in primary neuronal culture. The dissimilar cellular specificity of DLK and MLK3
and the specific substrate utilization and subcellular compartmentation of DLK
suggest that specific mixed lineage kinases participate in unique signal
transduction events.
PMID- 10187805
TI - Inhibition of receptor internalization by monodansylcadaverine selectively blocks
p55 tumor necrosis factor receptor death domain signaling.
AB - The 55-kDa receptor for tumor necrosis factor (TR55) triggers multiple signaling
cascades initiated by adapter proteins like TRADD and FAN. By use of the primary
amine monodansylcadaverine (MDC), we addressed the functional role of tumor
necrosis factor (TNF) receptor internalization for intracellular signal
distribution. We show that MDC does not prevent the interaction of the p55 TNF
receptor (TR55) with FAN and TRADD. Furthermore, the activation of plasmamembrane
associated neutral sphingomyelinase activation as well as the stimulation of
proline-directed protein kinases were not affected in MDC-treated cells. In
contrast, activation of signaling enzymes that are linked to the "death domain"
of TR55, like acid sphingomyelinase and c-Jun-N-terminal protein kinase as well
as TNF signaling of apoptosis in U937 and L929 cells, are blocked in the presence
of MDC. The results of our study suggest a role of TR55 internalization for the
activation of select TR55 death domain signaling pathways including those leading
to apoptosis.
PMID- 10187806
TI - Chloroquine binds in the cofactor binding site of Plasmodium falciparum lactate
dehydrogenase.
AB - Although the molecular mechanism by which chloroquine exerts its effects on the
malarial parasite Plasmodium falciparum remains unclear, the drug has previously
been found to interact specifically with the glycolytic enzyme lactate
dehydrogenase from the parasite. In this study we have determined the crystal
structure of the complex between chloroquine and P. falciparum lactate
dehydrogenase. The bound chloroquine is clearly seen within the NADH binding
pocket of the enzyme, occupying a position similar to that of the adenyl ring of
the cofactor. Chloroquine hence competes with NADH for binding to the enzyme,
acting as a competitive inhibitor for this critical glycolytic enzyme. Specific
interactions between the drug and amino acids unique to the malarial form of the
enzyme suggest this binding is selective. Inhibition studies confirm that
chloroquine acts as a weak inhibitor of lactate dehydrogenase, with mild
selectivity for the parasite enzyme. As chloroquine has been shown to accumulate
to millimolar concentrations within the food vacuole in the gut of the parasite,
even low levels of inhibition may contribute to the biological efficacy of the
drug. The structure of this enzyme-inhibitor complex provides a template from
which the quinoline moiety might be modified to develop more efficient inhibitors
of the enzyme.
PMID- 10187807
TI - Basolateral localization of fiber receptors limits adenovirus infection from the
apical surface of airway epithelia.
AB - Recent identification of two receptors for the adenovirus fiber protein,
coxsackie B and adenovirus type 2 and 5 receptor (CAR), and the major
histocompatibility complex (MHC) Class I alpha-2 domain allows the molecular
basis of adenoviral infection to be investigated. Earlier work has shown that
human airway epithelia are resistant to infection by adenovirus. Therefore, we
examined the expression and localization of CAR and MHC Class I in an in vitro
model of well differentiated, ciliated human airway epithelia. We found that
airway epithelia express CAR and MHC Class I. However, neither receptor was
present in the apical membrane; instead, both were polarized to the basolateral
membrane. These findings explain the relative resistance to adenovirus infection
from the apical surface. In contrast, when the virus was applied to the
basolateral surface, gene transfer was much more efficient because of an
interaction of adenovirus fiber with its receptors. In addition, when the
integrity of the tight junctions was transiently disrupted, apically applied
adenovirus gained access to the basolateral surface and enhanced gene transfer.
These data suggest that the receptors required for efficient infection are not
available on the apical surface, and interventions that allow access to the
basolateral space where fiber receptors are located increase gene transfer
efficiency.
PMID- 10187808
TI - A structure-based approach to designing non-natural peptides that can activate
anti-melanoma cytotoxic T cells.
AB - Tumor antigens presented by major histocompatibility complex (MHC) class I
molecules and recognized by CD8(+) cytotoxic T lymphocytes (CTLs) may generate an
efficient antitumor immune response after appropriate immunization. Antigenic
peptides can be used in vivo to induce antitumor or antiviral immunity. The
efficiency of naked peptides may be greatly limited by their degradation in the
biological fluids. We present a rational, structure-based approach to design
structurally modified, peptidase-resistant and biologically active analogues of
human tumor antigen MAGE-1.A1. This approach is based on our understanding of the
peptide interaction with the MHC and the T cell receptor and its precise
degradation pathway. Knowledge of these mechanisms led to the design of a non
natural, minimally modified analogue of MAGE-1.A1, [Aib2, NMe-Ser8]MAGE-1.A1,
which was highly peptidase-resistant and bound to MHC and activated MAGE-1.A1
specific anti-melanoma CTLs. Thus, we showed that it is possible to structurally
modify peptide epitopes to obtain analogues that are still specifically
recognized by CTLs. Such analogues may represent interesting leads for antitumor
synthetic vaccines.
PMID- 10187809
TI - Photocross-linking of the homing endonuclease PI-SceI to its recognition
sequence.
AB - PI-SceI is an intein-encoded protein that belongs to the LAGLIDADG family of
homing endonucleases. According to the crystal structure and mutational studies,
this endonuclease consists of two domains, one responsible for protein splicing,
the other for DNA cleavage, and both presumably for DNA binding. To define the
DNA binding site of PI-SceI, photocross-linking was used to identify amino acid
residues in contact with DNA. Sixty-three double-stranded oligodeoxynucleotides
comprising the minimal recognition sequence and containing single 5
iodopyrimidine substitutions in almost all positions of the recognition sequence
were synthesized and irradiated in the presence of PI-SceI with a helium/cadmium
laser (325 nm). The best cross-linking yield (approximately 30%) was obtained
with an oligodeoxynucleotide with a 5-iododeoxyuridine at position +9 in the
bottom strand. The subsequent analysis showed that cross-linking had occurred
with amino acid His-333, 6 amino acids after the second LAGLIDADG motif. With the
H333A variant of PI-SceI or in the presence of excess unmodified
oligodeoxynucleotide, no cross-linking was observed, indicating the specificity
of the cross-linking reaction. Chemical modification of His residues in PI-SceI
by diethylpyrocarbonate leads to a substantial reduction in the binding and
cleavage activity of PI-SceI. This inactivation can be suppressed by substrate
binding. This result further supports the finding that at least one His residue
is in close contact to the DNA. Based on these and published results, conclusions
are drawn regarding the DNA binding site of PI-SceI.
PMID- 10187810
TI - Identification of a surface of FNR overlapping activating region 1 that is
required for repression of gene expression.
AB - A library of Escherichia coli fnr mutants has been screened to identify FNR
(regulator of fumarate and nitrate reduction) variants that are defective
repressors, but competent activators. All but one of seventeen variants had
substitutions close to or within the face of FNR that contains activating region
1 (AR1). Activating region 1 is known to contact the alpha subunit of RNA
polymerase to facilitate transcription activation. It is now evident that this
face also has a role in FNR-mediated repression. Single amino acid substitutions
at Lys54, Gly74, Ala95, Met147, Leu193, Arg197, or Leu239, and double
substitutions at Ser13 and Ser145, Cys16 and Ile45, Tyr69 and Ser133, or Lys164
and Phe191, impaired FNR-mediated repression of ndh without greatly affecting
activation from model Class I (FNR site at -71.5) and Class II (FNR site at
41.5) FNR-activated promoters. Although repression was impaired in a second group
of FNR variants with substitutions at Leu34, Arg72 and Leu193, Phe92, or Ser178,
transcription activation from the simple FNR-dependent promoters was severely
reduced. However, expression from pyfiD (FNR sites at -40.5 and -93.5) and a
derivative lacking the site at -93.5, pyfiD-/+, remained relatively high
indicating that this second group have a context-dependent activation defect as
well as a repression defect. The prediction that the substitutions affecting
repression were likely to be in solvent exposed regions of FNR was supported by
analysis of peptides produced by partial proteolysis of FNR. Thus, FNR-mediated
repression at promoters with multiple FNR sites requires regions of FNR that are
different from, but overlap, AR1.
PMID- 10187811
TI - The transmembrane domain of the E5 oncoprotein contains functionally discrete
helical faces.
AB - The E5 protein of bovine papillomavirus is a 44-amino acid, Golgi-resident, type
II transmembrane protein that efficiently transforms immortalized mouse
fibroblasts. The transmembrane (TM) domain of E5 is not only critical for
biological activity, it also regulates interactions with cellular targets
including the platelet derived growth factor receptor (PDGF-R) and the 16-kDa
subunit of the vacuolar proton ATPase (V-ATPase). In order to define the specific
TM amino acids essential for E5 biological and biochemical activity, we performed
scanning alanine mutagenesis on 25 of the 30 potential TM residues and
genetically mapped discrete alpha-helical domains which separately regulated the
ability of E5 to bind PDGF-R, activate PDGF-R, and to form oligomers. Alanine
substitutions at positions 17, 21, and 24 (which lie on the same helical face)
greatly inhibited E5 association with the PDGF-R, suggesting that this region
comprises the receptor binding site. PDGF-R activation also mapped to a specific
but broader domain in E5; mutant proteins with alanines on one helical face
(positions 8, 9, 11, 16, 19, 22, and 23) continued to induce PDGF-R tyrosine
phosphorylation, whereas mutant proteins with alanines on the opposite helical
face (positions 7, 10, 13, 17, 18, 21, 24, and 25) did not, indicating that the
latter helical face was critical for mediating receptor transphosphorylation.
Interestingly, these "activation-defective" mutants segregated into two classes:
1) those that were unable to form dimers but that could still form higher order
oligomers and transform cells, and 2) those that were defective for PDGF-R
binding and were transformation-incompetent. These findings suggest that the
ability of E5 to dimerize and to bind PDGF-R is important for receptor
activation. However, since several transformation-competent E5 mutants were
defective for binding and/or activating PDGF-R, it is apparent that E5 must have
additional activities to mediate cell transformation. Finally, alanine
substitutions also defined two separate helical faces critical for E5/E5
interactions (homodimer formation). Thus, our data identify distinct E5 helical
faces that regulate homologous and heterologous intramembrane interactions and
define two new classes of biologically active TM mutants.
PMID- 10187812
TI - Spi-C, a novel Ets protein that is temporally regulated during B lymphocyte
development.
AB - A novel Ets protein was isolated by yeast one-hybrid screening of a cDNA library
made from lipopolysaccharide-stimulated mouse splenic B cells, using the SP6
kappa promoter kappaY element as a bait. The novel Ets protein was most closely
related to PU.1 and Spi-B within the DNA binding Ets domain and was therefore
named Spi-C. However, Spi-C may represent a novel subgroup within the Ets protein
family, as it differed significantly from Spi-B and PU.1 within helix 1 of the
Ets domain. Spi-C was encoded by a single-copy gene that was mapped to chromosome
10, region C. Spi-C interacted with DNA similarly to PU.1 as judged by
methylation interference, band-shift and site selection analysis, and activated
transcription of a kappaY element reporter gene upon co-transfection of HeLa
cells. Spi-C RNA was expressed in mature B lymphocytes and at lower levels in
macrophages. Furthermore, pre-B cell and plasma cell lines were Spi-C-negative,
suggesting that Spi-C might be a regulatory molecule during a specific phase of B
lymphoid development.
PMID- 10187813
TI - Oxidation of methionine residues in antithrombin. Effects on biological activity
and heparin binding.
AB - Commercially available human plasma-derived preparations of the serine protease
inhibitor antithrombin (AT) were shown to contain low levels of oxidation, and we
sought to determine whether oxidation might be a means of regulating the
protein's inhibitory activity. A recombinant form of AT, with similarly low
levels of oxidation as purified, was treated with hydrogen peroxide in order to
study the effect of oxidation, specifically methionine oxidation, on the
biochemical properties of this protein. AT contains two adjacent methionine
residues near the reactive site loop cleaved by thrombin (Met314 and Met315) and
two exposed methionines that border on the heparin binding region of AT (Met17
and Met20). In forced oxidations with hydrogen peroxide, the methionines at 314
and 315 were found to be the most susceptible to oxidation, but their oxidation
did not affect either thrombin-inhibitory activity or heparin binding.
Methionines at positions 17 and 20 were significantly oxidized only at higher
concentrations of peroxide, at which point heparin affinity was decreased.
However at saturating heparin concentrations, activity was only marginally
decreased for these highly oxidized samples of AT. Structural studies indicate
that highly oxidized AT is less able to undergo the complete conformational
change induced by heparin, most probably due to oxidation of Met17. Since this
does not occur in less oxidized, and presumably more physiologically relevant,
forms of AT such as those found in plasma preparations, oxidation does not appear
to be a means of controlling AT activity.
PMID- 10187814
TI - Multiple distinct coiled-coils are involved in dynamin self-assembly.
AB - Dynamin, a 100-kDa GTPase, has been implicated to be involved in synaptic vesicle
recycling, receptor-mediated endocytosis, and other membrane sorting processes.
Dynamin self-assembles into helical collars around the necks of coated pits and
other membrane invaginations and mediates membrane scission. In vitro, dynamin
has been reported to exist as dimers, tetramers, ring-shaped oligomers, and
helical polymers. In this study we sought to define self-assembly regions in
dynamin. Deletion of two closely spaced sequences near the dynamin-1 C terminus
abolished self-association as assayed by co-immunoprecipitation and the yeast
interaction trap, and reduced the sedimentation coefficient from 7.5 to 4.5 S.
Circular dichroism spectroscopy and equilibrium ultracentrifugation of synthetic
peptides revealed coiled-coil formation within the C-terminal assembly domain and
at a third, centrally located site. Two of the peptides formed tetramers,
supporting a role for each in the monomer-tetramer transition and providing novel
insight into the organization of the tetramer. Partial deletions of the C
terminal assembly domain reversed the dominant inhibition of endocytosis by
dynamin-1 GTPase mutants. Self-association was also observed between different
dynamin isoforms. Taken altogether, our results reveal two distinct coiled-coil
containing assembly domains that can recognize other dynamin isoforms and mediate
endocytic inhibition. In addition, our data strongly suggests a parallel model
for dynamin subunit self-association.
PMID- 10187815
TI - mE10, a novel caspase recruitment domain-containing proapoptotic molecule.
AB - Apoptotic signaling is mediated by homophilic interactions between conserved
domains present in components of the death pathway. The death domain, death
effector domain, and caspase recruitment domain (CARD) are examples of such
interaction motifs. We have identified a novel mammalian CARD-containing adaptor
molecule termed mE10 (mammalian E10). The N-terminal CARD of mE10 exhibits
significant homology (47% identity and 64% similarity) to the CARD of a gene from
Equine Herpesvirus type 2. The C-terminal region is unique. Overexpression of
mE10 in MCF-7 human breast carcinoma cells induces apoptosis. Mutational analysis
indicates that CARD-mediated mE10 oligomerization is essential for killing
activity. The C terminus of mE10 bound to the zymogen form of caspase-9 and
promoted its processing to the active dimeric species. Taken together, these data
suggest a model where autoproteolytic activation of pro-caspase-9 is mediated by
mE10-induced oligomerization.
PMID- 10187816
TI - Regulation of DNA binding activity and nuclear transport of B-Myb in Xenopus
oocytes.
AB - DNA binding activity and nuclear transport of B-Myb in Xenopus oocytes are
negatively regulated. Two distinct sequence elements in the C-terminal portion of
the protein are responsible for these different inhibitory activities. A C
terminal Xenopus B-Myb protein fragment inhibits the DNA binding activity of the
N-terminal repeats in trans, indicating that intramolecular folding may result in
masking of the DNA binding function. Xenopus B-Myb contains two separate nuclear
localization signals (NLSs), which, in Xenopus oocytes, function only outside the
context of the full-length protein. Fusion of an additional NLS to the full
length protein overcomes the inhibition of nuclear import, suggesting that
masking of the NLS function rather than cytoplasmic anchoring is responsible for
the negative regulation of Xenopus B-Myb nuclear transfer. During Xenopus
embryogenesis, when inhibition of nuclear import is relieved, Xenopus B-myb is
preferentially expressed in the developing nervous system and neural crest cells.
Within the developing neural tube, Xenopus B-myb gene transcription occurs
preferentially in proliferating, non-differentiated cells.
PMID- 10187817
TI - Molecular cloning and characterization of two novel pro-apoptotic isoforms of
caspase-10.
AB - Caspase-10/a (Mch4) and caspase-10/b (FLICE2) are related death effector domain
containing cysteine aspartases presumed to be at or near the apex of apoptotic
signaling pathways. We report the cloning and characterization of two novel
proteins that are splice isoforms of the caspase-10 family. Caspase-10/c is a
truncated protein that is essentially a prodomain-only form of the caspase that
lacks proteolytic activity in vitro but efficiently induces the formation of
perinuclear filamentous structures and cell death in vivo. Caspase-10/c mRNA is
specifically up-regulated upon TNF stimulation, suggesting a potential role of
this isoform in amplifying the apoptotic response to extracellular stimuli such
as cytokines. Caspase-10/d is a hybrid of the known caspases Mch4 and FLICE2, as
it is identical to FLICE2 except for the small (p12) catalytic subunit, which is
identical to Mch4. Caspase-10/d is proteolytically active in vitro and also
induces cell death in vivo, although it is less active than Mch4. The mRNAs for
all known isoforms of caspase-10 are abundantly expressed in fetal lung, kidney,
and skeletal muscle but are very poorly expressed or absent in these tissues in
the adult, implying a possible role for the caspase-10 family in fetal
development.
PMID- 10187818
TI - Preferential expression of biotransformation enzymes in the olfactory organs of
Drosophila melanogaster, the antennae.
AB - Biotransformation enzymes have been found in the olfactory epithelium of
vertebrates. We now show that in Drosophila melanogaster, a UDP
glycosyltransferase (UGT), as well as a short chain dehydrogenase/reductase and a
cytochrome P450 are expressed specifically or preferentially in the olfactory
organs, the antennae. The evolutionarily conserved expression of
biotransformation enzymes in olfactory organs suggests that they play an
important role in olfaction. In addition, we describe five Drosophila UGTs
belonging to two families. All five UGTs contain a putative transmembrane domain
at their C terminus as is the case for vertebrate UGTs where it is required for
enzymatic activity. The primary sequence of the C terminus, including part of the
transmembrane domain, differs between the two families but is highly conserved
not only within each Drosophila family, but also between the members of one of
the Drosophila families and vertebrate UGTs. The partial overlap of the conserved
primary sequence with the transmembrane domain suggests that this part of the
protein is involved in specific interactions occurring at the membrane surface.
The presence of different C termini in the two Drosophila families suggests that
they interact with different targets, one of which is conserved between
Drosophila and vertebrates.
PMID- 10187819
TI - Regulation of forestomach-specific expression of the murine adenosine deaminase
gene.
AB - The maturation of stratified squamous epithelium of the upper gastrointestinal
tract is a highly ordered process of development and differentiation. Information
on the molecular basis of this process is, however, limited. Here we report the
identification of the first murine forestomach regulatory element using the
murine adenosine deaminase (Ada) gene as a model. In the adult mouse, Ada is
highly expressed in the terminally differentiated epithelial layer of upper
gastrointestinal tract tissues. The data reported here represent the
identification and detailed analysis of a 1. 1-kilobase (kb) sequence located 3.4
kb upstream of the transcription initiation site of the murine Ada gene, which is
sufficient to target cat reporter gene expression to the forestomach in
transgenic mice. This 1.1-kb fragment is capable of directing cat reporter gene
expression mainly to the forestomach of transgenic mice, with a level comparable
to the endogenous Ada gene. This expression is localized to the appropriate cell
types, confers copy number dependence, and shows the same developmental
regulation. Mutational analysis revealed the functional importance of multiple
transcription factor-binding sites.
PMID- 10187820
TI - Description of a versatile peroxidase involved in the natural degradation of
lignin that has both manganese peroxidase and lignin peroxidase substrate
interaction sites.
AB - Two major peroxidases are secreted by the fungus Pleurotus eryngii in
lignocellulose cultures. One is similar to Phanerochaete chrysosporium manganese
dependent peroxidase. The second protein (PS1), although catalyzing the oxidation
of Mn2+ to Mn3+ by H2O2, differs from the above enzymes by its manganese
independent activity enabling it to oxidize substituted phenols and synthetic
dyes, as well as the lignin peroxidase (LiP) substrate veratryl alcohol. This is
by a mechanism similar to that reported for LiP, as evidenced by p
dimethoxybenzene oxidation yielding benzoquinone. The apparent kinetic constants
showed high activity on Mn2+, but methoxyhydroquinone was the natural substrate
with the highest enzyme affinity (this and other phenolic substrates are not
efficiently oxidized by the P. chrysosporium peroxidases). A three-dimensional
model was built using crystal models from four fungal peroxidase as templates.
The model suggests high structural affinity of this versatile peroxidase with LiP
but shows a putative Mn2+ binding site near the internal heme propionate,
involving Glu36, Glu40, and Asp181. A specific substrate interaction site for
Mn2+ is supported by kinetic data showing noncompetitive inhibition with other
peroxidase substrates. Moreover, residues reported as involved in LiP interaction
with veratryl alcohol and other aromatic substrates are present in peroxidase PS1
such as His82 at the heme-channel opening, which is remarkably similar to that of
P. chrysosporium LiP, and Trp170 at the protein surface. These residues could be
involved in two different hypothetical long range electron transfer pathways from
substrate (His82-Ala83-Asn84-His47-heme and Trp170-Leu171-heme) similar to those
postulated for LiP.
PMID- 10187821
TI - Transmembrane helix 7 of the endothelin B receptor regulates downstream
signaling.
AB - Endothelin is a 21-amino acid peptide with a striking diversity of important
biological responses, including, vasoconstriction, bronchoconstriction, and
mitogenesis. Endothelin-1 binding to the endothelin B receptor (ETB), a member of
the superfamily of G-protein-coupled receptors, was associated with catalytic
activation of the extracellular-regulated kinase 2 (ERK2) and stimulation of AP-1
transcriptional reporter activity. A panel of single point mutations in
transmembrane helix 6 (TM6), intracellular loop 3, and transmembrane helix 7
(TM7) were developed to study the structural requirements for ETB activation.
Point mutations within highly conserved regions of TM6 and intracellular loop 3
were without effect on agonist-stimulated ERK activation. However, mutations
within TM7 of the ETB significantly impacted ligand-stimulated downstream
signaling. For example, nine point mutations within TM7 of the ETB were
identified that prevented endothelin-stimulated ERK activation. Interestingly,
the TM7 mutants fell into two classes; several exhibited greatly decreased AP-1
activity, relative to wild type ETB, whereas others displayed augmented
endothelin-stimulated AP-1 transcriptional activity relative to wild type ETB.
Our results suggest that TM7 of the ETB is involved in its activation mechanism
and regulates agonist-stimulated ERK activation.
PMID- 10187822
TI - Two E2F sites control growth-regulated and cell cycle-regulated transcription of
the Htf9-a/RanBP1 gene through functionally distinct mechanisms.
AB - The gene encoding Ran-binding protein 1 (RanBP1) is transcribed in a cell cycle
dependent manner. The RanBP1 promoter contains two binding sites for E2F factors,
named E2F-c, located proximal to the transcription start, and E2F-b, falling in a
more distal promoter region. We have now induced site-directed mutagenesis in
both sites. We have found that the distal E2F-b site, together with a neighboring
Sp1 element, actively controls up-regulation of transcription in S phase. The
proximal E2F-c site plays no apparent role in cycling cells yet is required for
transcriptional repression upon growth arrest. Protein binding studies suggest
that each E2F site mediates specific interactions with individual E2F family
members. In addition, transient expression assays with mutagenized promoter
constructs indicate that the functional role of each site is also dependent on
its position relative to other regulatory elements in the promoter context. Thus,
the two E2F sites play opposite genetic functions and control RanBP1
transcription through distinct molecular mechanisms.
PMID- 10187823
TI - Acetaminophen toxicity. Opposite effects of two forms of glutathione peroxidase.
AB - Acetaminophen is one of the most extensively used analgesics/antipyretics
worldwide, and overdose or idiopathic reaction causes major morbidity and
mortality in its victims. Research into the mechanisms of toxicity and possible
therapeutic intervention is therefore essential. In this study, the response of
transgenic mice overexpressing human antioxidant enzymes to acute acetaminophen
overdose was investigated. Animals overexpressing superoxide dismutase or plasma
glutathione peroxidase demonstrated dramatic resistance to acetaminophen
toxicity. Intravenous injection of glutathione peroxidase provided normal mice
with nearly complete protection against a lethal dose of acetaminophen.
Surprisingly, animals overexpressing intracellular glutathione peroxidase in the
liver were significantly more sensitive to acetaminophen toxicity compared with
nontransgenic littermates. This sensitivity appears to be due to the inability of
these animals to efficiently recover glutathione depleted as a result of
acetaminophen metabolism. Finally, the results suggest that glutathione
peroxidase overexpression modulates the synthesis of several acetaminophen
metabolites. Our results demonstrate the ability of glutathione peroxidase levels
to influence the outcome of acetaminophen toxicity.
PMID- 10187824
TI - In vitro analysis of the interaction between the FinO protein and FinP antisense
RNA of F-like conjugative plasmids.
AB - The FinO protein regulates the transfer potential of F-like conjugative plasmids
through its interaction with FinP antisense RNA and its target, traJ mRNA. FinO
binds to and protects FinP from degradation and promotes duplex formation between
FinP and traJ mRNA in vitro. The FinP secondary structure consists of two stem
loop domains separated by a 4-base spacer and terminated by a 6-base tail.
Previous studies suggested FinO bound to the smooth 14-base pair helix of stem
loop II. In this investigation, RNA mobility shift analysis was used to study the
interaction between a glutathione S-transferase (GST)-FinO fusion protein and a
series of synthetic FinP and traJ mRNA variants. Mutations in 16 of the 28 bases
in stem II of FinP that are predicted to disrupt base pairing did not
significantly alter the GST-FinO binding affinity. Removal of the single-stranded
regions on either side of stem-loop II led to a dramatic decrease in GST-FinO
binding to FinP and to the complementary region of the traJ mRNA leader. While no
evidence for sequence-specific contacts was found, the results suggest that FinO
recognizes the overall shape of the RNA and is influenced by the length of the
single-stranded regions flanking the stem-loop.
PMID- 10187825
TI - Redox-dependent regulation of nuclear import of the glucocorticoid receptor.
AB - A number of transcription factors including the glucocorticoid receptor (GR) are
regulated in a redox-dependent fashion. We have previously reported that the
functional activity of the GR is suppressed under oxidative conditions and
restored in the presence of reducing reagents. In the present study, we have used
a chimeric human GR fused to the Aequorea green fluorescent protein and
demonstrated that both ligand-dependent and -independent nuclear translocation of
the GR is impaired under oxidative conditions in living cells. Substitution of
Cys-481 for Ser within NL1 of the human GR resulted in reduction of sensitivity
to oxidative treatment, strongly indicating that Cys-481 is one of the target
amino acids for redox regulation of the receptor. Taken together, we may conclude
that redox-dependent regulation of nuclear translocation of the GR constitutes an
important mechanism for modulation of glucocorticoid-dependent signal
transduction.
PMID- 10187826
TI - Keratinocyte collagenase-1 expression requires an epidermal growth factor
receptor autocrine mechanism.
AB - In response to cutaneous injury, expression of collagenase-1 is induced in
keratinocytes via alpha2beta1 contact with native type I collagen, and enzyme
activity is essential for cell migration over this substratum. However, the
cellular mechanism(s) mediating integrin signaling remain poorly understood. We
demonstrate here that treatment of keratinocytes cultured on type I collagen with
epidermal growth factor receptor (EGFR) blocking antibodies or a specific
receptor antagonist inhibited cell migration across type I collagen and the
matrix-directed stimulation of collagenase-1 production. Additionally,
stimulation of collagenase-1 expression by hepatocyte growth factor, transforming
growth factor-beta1, and interferon-gamma was blocked by EGFR inhibitors,
suggesting a required EGFR autocrine signaling step for enzyme expression.
Collagenase-1 mRNA was not detectable in keratinocytes isolated immediately from
normal skin, but increased progressively following 2 h of contact with collagen.
In contrast, EGFR mRNA was expressed at high steady-state levels in keratinocytes
isolated immediately from intact skin but was absent following 2 h cell contact
with collagen, suggesting down-regulation following receptor activation. Indeed,
tyrosine phosphorylation of the EGFR was evident as early as 10 min following
cell contact with collagen. Treatment of keratinocytes cultured on collagen with
EGFR antagonist or heparin-binding (HB)-EGF neutralizing antibodies dramatically
inhibited the sustained expression (6-24 h) of collagenase-1 mRNA, whereas
initial induction by collagen alone (2 h) was unaffected. Finally, expression of
collagenase-1 in ex vivo wounded skin and re-epithelialization of partial
thickness porcine burn wounds was blocked following treatment with EGFR
inhibitors. These results demonstrate that keratinocyte contact with type I
collagen is sufficient to induce collagenase-1 expression, whereas sustained
enzyme production requires autocrine EGFR activation by HB-EGF as an obligatory
intermediate step, thereby maintaining collagenase-1-dependent migration during
the re-epithelialization of epidermal wounds.
PMID- 10187827
TI - Repression of human fibroblast growth factor 2 by a novel transcription factor.
AB - Here we describe the cloning of the regulator of fibroblast growth factor 2 (FGF
2) transcription (RFT) using a yeast one-hybrid screening with a defined motif in
FGF-2 promoter as a target sequence. Overexpression of human RFT (RFT-A) reduces
FGF-2 RNA and protein levels in both normal and tumor cell lines. Its splice
variants, RFT-A' and RFT-B, have deletions in the putative DNA binding domain and
fail to bind FGF-2 promoter and repress FGF-2 gene expression. The ratios of RFT
isoforms differ between normal and tumor cells, with the splice variants
dominating in tumor cells. Overexpression of RFT-A induces glioma cell death. Our
data suggest that regulation of FGF-2 by RFT is important for cellular functions
and may be impaired in certain tumors.
PMID- 10187828
TI - Impaired membrane transport in methotrexate-resistant CCRF-CEM cells involves
early translation termination and increased turnover of a mutant reduced folate
carrier.
AB - The basis for impaired reduced folate carrier (RFC) activity in methotrexate
resistant CCRF-CEM (CEM/Mtx-1) cells was examined. Parental and CEM/Mtx-1 cells
expressed identical levels of the 3. 1-kilobase RFC transcript. A approximately
85-kDa RFC protein was detected in parental cells by photoaffinity labeling and
on Western blots with RFC-specific antiserum. In CEM/Mtx-1 cells, RFC protein was
undetectable. By reverse transcriptase-polymerase chain reaction and sequence
analysis, G to A point mutations were identified in CEM/Mtx-1 transcripts at
positions 130 (P1; changes glycine 44 --> arginine) and 380 (P2; changes serine
127 --> asparagine). A 4-base pair (CATG) insertion detected at position 191 (in
19-30% of cDNA clones) resulted in a frameshift and early translation
termination. Wild-type RFC was also detected (0-9% of clones). Wild-type RFC and
double-mutated RFC (RFCP1+P2) cDNAs were transfected into transport-impaired K562
and Chinese hamster ovary cells. Although RFC transcripts paralleled wild-type
protein, for the RFCP1+P2 transfectants, disproportionately low RFCP1+P2 protein
was detected. This reflected an increased turnover of RFCP1+P2 over wild-type
RFC. RFCP1+P2 did not restore methotrexate transport; however, uptake was
partially restored by constructs with single mutations at the P1 or P2 loci.
Cumulatively, our results show that loss of transport function in CEM/Mtx-1 cells
results from complete loss of RFC protein due to early translation termination
and increased turnover of a mutant RFC protein.
PMID- 10187829
TI - GroEL/GroES-dependent reconstitution of alpha2 beta2 tetramers of
humanmitochondrial branched chain alpha-ketoacid decarboxylase. Obligatory
interaction of chaperonins with an alpha beta dimeric intermediate.
AB - The decarboxylase component (E1) of the human mitochondrial branched chain alpha
ketoacid dehydrogenase multienzyme complex (approximately 4-5 x 10(3) kDa) is a
thiamine pyrophosphate-dependent enzyme, comprising two 45.5-kDa alpha subunits
and two 37.8-kDa beta subunits. In the present study, His6-tagged E1 alpha2 beta2
tetramers (171 kDa) denatured in 8 M urea were competently reconstituted in vitro
at 23 degrees C with an absolute requirement for chaperonins GroEL/GroES and Mg
ATP. Unexpectedly, the kinetics for the recovery of E1 activity was very slow
with a rate constant of 290 M-1 s-1. Renaturation of E1 with a similarly slow
kinetics was also achieved using individual GroEL-alpha and GroEL-beta complexes
as combined substrates. However, the beta subunit was markedly more prone to
misfolding than the alpha in the absence of GroEL. The alpha subunit was released
as soluble monomers from the GroEL-alpha complex alone in the presence of GroES
and Mg-ATP. In contrast, the beta subunit discharged from the GroEL-beta complex
readily rebound to GroEL when the alpha subunit was absent. Analysis of the
assembly state showed that the His6-alpha and beta subunits released from
corresponding GroEL-polypeptide complexes assembled into a highly structured but
inactive 85.5-kDa alpha beta dimeric intermediate, which subsequently dimerized
to produce the active alpha2 beta2 tetrameter. The purified alpha beta dimer
isolated from Escherichia coli lysates was capable of binding to GroEL to produce
a stable GroEL-alpha beta ternary complex. Incubation of this novel ternary
complex with GroES and Mg-ATP resulted in recovery of E1 activity, which also
followed slow kinetics with a rate constant of 138 M-1 s-1. Dimers were
regenerated from the GroEL-alpha beta complex, but they needed to interact with
GroEL/GroES again, thereby perpetuating the cycle until the conversion from
dimers to tetramers was complete. Our study describes an obligatory role of
chaperonins in priming the dimeric intermediate for subsequent tetrameric
assembly, which is a slow step in the reconstitution of E1 alpha2 beta2
tetramers.
PMID- 10187830
TI - Mechanisms for GroEL/GroES-mediated folding of a large 86-kDa fusion polypeptide
in vitro.
AB - Our understanding of mechanisms for GroEL/GroES-assisted protein folding to date
has been derived mostly from studies with small proteins. Little is known
concerning the interaction of these chaperonins with large multidomain
polypeptides during folding. In the present study, we investigated chaperonin
dependent folding of a large 86-kDa fusion polypeptide, in which the mature
maltose-binding protein (MBP) sequence was linked to the N terminus of the alpha
subunit of the decarboxylase (E1) component of the human mitochondrial branched
chain alpha-ketoacid dehydrogenase complex. The fusion polypeptide, MBP-alpha,
when co-expressed with the beta subunit of E1, produced a chimeric protein MBP-E1
with an (MBP-alpha)2beta2 structure, similar to the alpha2 beta2 structure in
native E1. Reactivation of MBP-E1 denatured in 8 M urea was absolutely dependent
on GroEL/GroES and Mg2+-ATP, and exhibited strikingly slow kinetics with a rate
constant of 376 M-1 s-1, analogous to denatured untagged E1. Chaperonin-mediated
refolding of the MBP-alpha fusion polypeptide showed that the folding of the MBP
moiety was about 7-fold faster than that of the alpha moiety on the same chain
with rate constants of 1.9 x 10(-3) s-1 and 2.95 x 10(-4) s-1, respectively. This
explained the occurrence of an MBP-alpha. GroEL binary complex that was isolated
with amylose resin from the refolding mixture and transformed Escherichia coli
lysates. The data support the thesis that distinct functional sequences in a
large polypeptide exhibit different folding characteristics on the same GroEL
scaffold. Moreover, we show that when the alpha.GroEL complex (molar ratio 1:1)
was incubated with GroES, the latter was capable of capping either the very ring
that harbored the 48-kDa (His)6-alpha polypeptide (in cis) or the opposite
unoccupied cavity (in trans). In contrast, the MBP-alpha.GroEL (1:1) complex was
capped by GroES exclusively in the trans configuration. These findings suggest
that the productive folding of a large multidomain polypeptide can only occur in
the GroEL cavity that is not sequestered by GroES.
PMID- 10187831
TI - A different intracellular distribution of a single reporter protein is determined
at steady state by KKXX or KDEL retrieval signals.
AB - To establish the specific contribution to protein topology of KKXX and KDEL
retrieval motifs, we have determined by immunogold electron microscopy and cell
fractionation the intracellular distribution at steady state of the transmembrane
and anchorless versions of human CD8 protein, tagged with KKXX (CD8-E19) and KDEL
(CD8-K), respectively, and stably expressed in epithelial rat cells (Martire, G.,
Mottola, G., Pascale, M. C., Malagolini, N., Turrini, I., Serafini-Cessi, F.,
Jackson, M. R., and Bonatti, S. (1996) J. Biol. Chem. 271, 3541-3547). The CD8
E19 protein is represented by a single form, initially O-glycosylated: only about
half of it is located in the endoplasmic reticulum, whereas more than 30% of the
total is present in the intermediate compartment and cis-Golgi complex. In the
latter compartments, CD8-E19 colocalizes with beta-coat protein (COP) (COPI
component) and shows the higher density of labeling. Conversely, about 90% of the
total CD8-KDEL protein is localized in clusters on the endoplasmic reticulum,
where significant co-localization with Sec-23p (COPII component) is observed, and
unglycosylated and initially O-glycosylated forms apparently constitute a single
pool. Altogether, these results suggest that KKXX and KDEL retrieval motifs have
different topological effects on theirs own at steady state: the first results in
a specific enrichment in the intermediate compartment and cis-Golgi complex, and
the latter dictates residency in the endoplasmic reticulum.
PMID- 10187832
TI - Identification of a novel DNA binding site for nuclear orphan receptor OR1.
AB - The nuclear orphan receptor OR1 has been shown to bind as a heterodimer with
retinoid X receptor (RXR) to direct repeat 4 (DR4) response elements. It remained
unclear, however, whether this represents the only or the optimal binding site
for this receptor. Therefore, we performed a DNA binding site selection assay
that allows the identification of novel DNA binding sites for OR1 in an unbiased
manner. While OR1 alone was not able to select a specific sequence from the pool
of oligonucleotides, the OR1/RXR heterodimer selected a highly conserved DR1
element, termed DR1s, with two AGGTCA motifs spaced by one adenosine. The
functional activity of the consensus binding site was verified in transient
transfection assays and corroborated by in vitro studies. Based on the sequence
of the consensus DR1s, we located putative natural binding sites in the 5'
promoter flanking regions of the rat S14 gene and the rat cholecystokinin type A
receptor gene. Furthermore, we could show that although the OR1/RXR heterodimer
has a distinct binding orientation on a DR4 element, it is able to bind in both
orientations to the DR1s element. The OR1 paralog LXRalpha does not bind as a
heterodimer with RXR to the DR1s element, indicating that these receptors,
despite their homology, are involved in the regulation of different sets of
genes.
PMID- 10187833
TI - Protein kinase inhibitor H7 blocks the induction of immediate-early genes zif268
and c-fos by a mechanism unrelated to inhibition of protein kinase C but possibly
related to inhibition of phosphorylation of RNA polymerase II.
AB - 1-(5-Isoquinolinesulfonyl)-2-methylpiperazine (H7) has often been used in
combination with protein kinase inhibitor (N-(2-guanidinoethyl)-5
isoquinolinesulfonamide) (HA1004) to assess the contribution of protein kinase C
(PKC) to cellular processes, including the induction of gene expression. This use
of H7 and HA1004 is based upon the fact that H7 inhibits PKC more potently than
HA1004 in in vitro assays. Thus, although both compounds are broad spectrum
protein kinase inhibitors, inhibition by H7, but not by HA1004, has often been
interpreted as evidence for the involvement of PKC in the cellular process under
study. Here we describe experiments that show that this interpretation is not
correct with regard to the induction of two immediate-early genes, zif268 and c
fos, in PC12D cells. In these studies we confirmed that H7, but not HA1004,
potently blocks the induction of zif268 and c-fos mRNA by nerve growth factor,
carbachol, phorbol ester, Ca2+ ionophore, or forskolin. Surprisingly, however, H7
has no effect on the ability of these agents to activate mitogen-activated
protein kinase (MAPK), an upstream activator of zif268 and c-fos gene expression.
H7 also does not inhibit preactivated MAPK in vitro. Taken together, these
results suggest that H7 blocks gene expression by acting at a site downstream
from MAPK. H7 has previously been shown to block transcription in vitro by
blocking the phosphorylation of the carboxyl-terminal domain of RNA polymerase II
(Yankulov, K., Yamashita, K., Roy, R., Egly, J.-M., and Bentley, D. L.(1995) J.
Biol. Chem. 270, 23922-23925). In this study, we show that pretreating PC12D
cells with H7, but not with HA1004, significantly reduces levels of
phosphorylated RNA polymerase II in vivo. These results suggest that H7 blocks
gene expression by inhibiting the phosphorylation of RNA polymerase II, a step
required for progression from transcription initiation to mRNA chain elongation.
PMID- 10187834
TI - The gain-of-function Chinese hamster ovary mutant LEC11B expresses one of two
Chinese hamster FUT6 genes due to the loss of a negative regulatory factor.
AB - The LEC11 Chinese hamster ovary (CHO) gain-of-function mutant expresses an
alpha(1,3)fucosyltransferase (alpha(1,3)Fuc-T) activity that generates the LeX,
sialyl-LeX, and VIM-2 glycan determinants and has been extensively used for
studies of E-selectin ligand specificity. In order to identify regulatory
mechanisms that control alpha(1,3)Fuc-T expression in mammals, mechanisms of FUT
gene expression were investigated in LEC11 cells and two new, independent
mutants, LEC11A and LEC11B. Northern and ribonuclease protection analyses, using
probes that span the coding region of a cloned CHO FUT gene, detected transcripts
in each LEC11 mutant but not in CHO cells or other gain-of-function CHO mutants
that express a different alpha(1,3)Fuc-T activity. Coding region sequence
analysis and alpha(1,3)Fuc-T acceptor specificity comparisons with recombinant
human Fuc-TV and Fuc-TVI showed that the cloned FUT gene is orthologous to the
human FUT6 gene. Southern analyses identified two closely related FUT6 genes in
the Chinese hamster, whose evolutionary relationships are discussed. The blots
showed that rearrangements had occurred in LEC11A and LEC11 genomic DNA,
consistent with a cis mechanism of FUT6 gene activation in these mutants. By
contrast, somatic cell hybrid analyses revealed that LEC11B cells express FUT6
gene transcripts due to the loss of a trans-acting, negative regulatory factor.
Sequencing of reverse transcriptase-polymerase chain reaction products identified
unique 5'- and 3'-untranslated region sequences in FUT6 gene transcripts from
each LEC11 mutant. Northern and Southern analyses with gene-specific probes
showed that LEC11A cells express only the cgFUT6A gene (where cg is Cricetulus
griseus), whereas LEC11 and LEC11B cells express only the cgFUT6B gene. In LEC11A
x LEC11B hybrid cells, the cgFUT6A gene was predominantly expressed, as predicted
if a trans-acting negative regulatory factor functions to suppress cgFUT6B gene
expression in CHO cells. This factor is predicted to be a cell type-specific
regulator of FUT6 gene expression in mammals.
PMID- 10187835
TI - Mutagenesis of an arginine- and lysine-rich domain in the gp91(phox) subunit of
the phagocyte NADPH-oxidase flavocytochrome b558.
AB - Site-directed mutagenesis was used to generate a series of mutants harboring
point or multiple substitutions within the hydrophilic, polybasic domain of
gp91(phox) encompassed by residues 86-102, which was previously identified as a
site of interaction with p47(phox) during phagocyte NADPH oxidase assembly.
Recombinant wild-type or mutant gp91(phox) was expressed in a human myeloid
leukemia cell line in which the endogenous gp91(phox) gene was disrupted by gene
targeting. NADPH oxidase activity was measured in a cytochrome c reduction assay
following granulocytic differentiation of cells that expressed recombinant
gp91(phox). Expression of a gp91(phox) mutant in which amino acids 89-97 were
replaced with nine alternate amino acids abolished NADPH oxidase activity.
Expression of gp91(phox) mutants R89T, D95A, D95R, R96A, R96E, or K102T did not
significantly affect NADPH oxidase activity. However, mutations of individual or
paired arginine residues at positions 91 and 92 had substantial effects on
superoxide generation. The R91E/R92E mutation completely abolished both NADPH
oxidase activity and membrane-translocation of the cytosolic oxidase proteins
p47(phox), p67(phox), Rac1, and Rac2. The phorbol 12-myristate 13-acetate-induced
rate of superoxide production was reduced by approximately 75% in cells
expressing R91T/R92A, R91E, or R92E gp91(phox) along with an increased lag time
to the maximal rates of superoxide production relative to cells expressing wild
type gp91(phox). Taken together, these results demonstrate that Arg91 and Arg92
of gp91(phox) are essential for flavocytochrome b558 function in granulocytes and
suggest that these residues participate in the interaction of gp91(phox) with the
cytosolic oxidase proteins.
PMID- 10187836
TI - Determination of the stoichiometry and strength of binding of xanthophylls to the
photosystem II light harvesting complexes.
AB - Xanthophylls have a crucial role in the structure and function of the light
harvesting complexes of photosystem II (LHCII) in plants. The binding of
xanthophylls to LHCII has been investigated, particularly with respect to the
xanthophyll cycle carotenoids violaxanthin and zeaxanthin. It was found that most
of the violaxanthin pool was loosely bound to the major complex and could be
removed by mild detergent treatment. Gentle solubilization of photosystem II
particles and thylakoids allowed the isolation of complexes, including a newly
described oligomeric preparation, enriched in trimers, that retained all of the
in vivo violaxanthin pool. It was estimated that each LHCII monomer can bind at
least one violaxanthin. The extent to which different pigments can be removed
from LHCII indicated that the relative strength of binding was chlorophyll b >
neoxanthin > chlorophyll a > lutein > zeaxanthin > violaxanthin. The xanthophyll
binding sites are of two types: internal sites binding lutein and peripheral
sites binding neoxanthin and violaxanthin. In CP29, a minor LHCII, both a lutein
site and the neoxanthin site can be occupied by violaxanthin. Upon activation of
the violaxanthin de-epoxidase, the highest de-epoxidation state was found for the
main LHCII component and the lowest for CP29, suggesting that only violaxanthin
loosely bound to LHCII is available for de-epoxidation.
PMID- 10187837
TI - Photosystem I is indispensable for photoautotrophic growth, CO2 fixation, and H2
photoproduction in Chlamydomonas reinhardtii.
AB - Certain Chlamydomonas reinhardtii mutants deficient in photosystem I due to
defects in psaA mRNA maturation have been reported to be capable of CO2 fixation,
H2 photoevolution, and photoautotrophic growth (Greenbaum, E., Lee, J. W.,
Tevault, C. V., Blankinship, S. L. , and Mets, L. J. (1995) Nature 376, 438-441
and Lee, J. W., Tevault, C. V., Owens, T. G.; Greenbaum, E. (1996) Science 273,
364-367). We have generated deletions of photosystem I core subunits in both wild
type and these mutant strains and have analyzed their abilities to grow
photoautotrophically, to fix CO2, and to photoevolve O2 or H2 (using mass
spectrometry) as well as their photosystem I content (using immunological and
spectroscopic analyses). We find no instance of a strain that can perform
photosynthesis in the absence of photosystem I. The F8 strain harbored a small
amount of photosystem I, and it could fix CO2 and grow slowly, but it lost these
abilities after deletion of either psaA or psaC; these activities could be
restored to the F8-psaADelta mutant by reintroduction of psaA. We observed
limited O2 photoevolution in mutants lacking photosystem I; use of 18O2 indicated
that this O2 evolution is coupled to O2 uptake (i.e. respiration) rather than CO2
fixation or H2 evolution. We conclude that the reported instances of CO2
fixation, H2 photoevolution, and photoautotrophic growth of photosystem I
deficient mutants result from the presence of unrecognized photosystem I.
PMID- 10187838
TI - Molecular cloning and characterization of a human uronyl 2-sulfotransferase that
sulfates iduronyl and glucuronyl residues in dermatan/chondroitin sulfate.
AB - A partial-length human cDNA with a predicted amino acid sequence homologous to a
previously described heparan sulfate iduronyl 2-sulfotransferase (Kobayashi, M.,
Habuchi, H., Yoneda, M., Habuchi, O., and Kimata, K. (1997) J. Biol. Chem. 272,
13980-13985) was obtained by searching the expressed sequence-tagged data bank.
Northern blot analysis was performed using this homologous cDNA as a probe, which
demonstrated ubiquitous expression of messages of 5.1 and 2.0 kilobases in a
number of human tissues and in several human cancer cell lines. Since the human
lymphoma Raji cell line had the highest level of expression, it was used to
isolate a full-length cDNA clone. The full-length cDNA was found to contain an
open reading frame that predicted a type II transmembrane protein composed of 406
amino acid residues. The cDNA in a baculovirus expression vector was expressed in
Sf9 insect cells, and cell extracts were then incubated together with 3'
phosphoadenosine 5'-phospho[35S]sulfate and potential glycosaminoglycan
acceptors. This demonstrated substantial sulfotransferase activity with dermatan
sulfate, a small degree of activity with chondroitin sulfate, but no
sulfotransferase activity with desulfated N-resulfated heparin. Analysis of
[35S]sulfate-labeled disaccharide products of chondroitin ABC, chondroitin AC,
and chondroitin B lyase treatment demonstrated that the enzyme only transferred
sulfate to the 2-position of uronyl residues, which were preponderantly iduronyl
residues in dermatan sulfate, but some lesser transfer to glucuronyl residues of
chondroitin sulfate.
PMID- 10187839
TI - Proline-rich motifs of the Na+/H+ exchanger 2 isoform. Binding of Src homology
domain 3 and role in apical targeting in epithelia.
AB - The NHE2 isoform of the Na+/H+ exchanger (NHE) displays two proline-rich
sequences in its C-terminal region that resemble SH3 (Src homology 3)-binding
domains. We investigated whether these regions (743PPSVTPAP750, termed Pro-1, and
786VPPKPPP792, termed Pro-2) can bind to SH3 domains and whether they are
essential for NHE2 function and targeting. A fusion protein containing the Pro-1
region showed promiscuous binding to SH3 domains of several proteins in vitro,
whereas a Pro-2 fusion bound preferentially to domains derived from kinases. In
contrast, cytoplasmic regions of NHE1, NHE3, or NHE4 failed to interact. When
expressed in antiporter-deficient cells, truncated NHE2 lacking both Pro-rich
regions catalyzed Na+/H+ exchange, retained sensitivity to intracellular ATP, and
was activated by hyperosmolarity, resembling full-length NHE2. The role of the
Pro-rich regions in subcellular targeting was examined by transfection of epitope
tagged forms of NHE2 in porcine renal epithelial LLC-PK1 cells. Both full-length
and Pro-2-truncated NHE2 localized almost exclusively to the apical membrane. By
contrast, a mutant devoid of both Pro-1 and Pro-2 was preferentially sorted to
the basolateral surface but also accumulated intracellularly. These observations
indicate that the region encompassing Pro-1 is essential for appropriate
subcellular targeting of NHE2.
PMID- 10187840
TI - Disruption of gap junctional communication by the platelet-derived growth factor
is mediated via multiple signaling pathways.
AB - The platelet-derived growth factor (PDGF) mediates its cellular functions via
activation of its receptor tyrosine kinase followed by the recruitment and
activation of several signaling molecules. These signaling molecules then
initiate specific signaling cascades, finally resulting in distinct physiological
effects. To delineate the PDGF signaling pathway responsible for the disruption
of gap junctional communication (GJC), wild-type PDGF receptor beta (PDGFRbeta)
and a series of PDGFRbeta mutants were expressed in T51B rat liver epithelial
cells. In cells expressing wild-type PDGFRbeta, PDGF induced disruption of GJC
and phosphorylation of a gap junctional protein, connexin-43 (Cx43), which
required activation of mitogen-activated protein kinase, although involvement of
additional factors was also evident. In the F5 mutant lacking binding sites for
phosphatidylinositol 3-kinase, GTPase-activating protein, SHP-2, and
phospholipase Cgamma1 (PLCgamma1), PDGF induced mitogen-activated protein kinase,
but failed to affect GJC or Cx43, indicating involvement of additional signals
presumably initiated by one or more of the mutated binding sites. Examination of
the single-site mutants revealed that PDGF effects were not mediated via a single
signaling component. This was confirmed by the "add-back" mutants, which showed
that restoration of either SHP-2 or PLCgamma1 binding was sufficient to propagate
the GJC inhibitory actions of PDGF. Further analysis showed that activation of
PLCgamma1 is involved in Cx43 phosphorylation, which surprisingly failed to
correlate with GJC blockade. The results of our study demonstrate that PDGF
induced disruption of GJC can be mediated by multiple signaling pathways and
requires participation of multiple components.
PMID- 10187841
TI - Reactive site-modified tissue inhibitor of metalloproteinases-2 inhibits the cell
mediated activation of progelatinase A.
AB - Tissue inhibitor of metalloproteinases-2 (TIMP-2) is supposed to play a
regulatory role in the cell-mediated activation of progelatinase A. To
investigate the mechanism of the regulation, we prepared and characterized a
chemically modified TIMP-2, and examined its effects on the activation of
progelatinase A. We found that treatment of TIMP-2 with cyanate ion led to loss
of inhibitory activity toward matrilysin or gelatinase A. Structural and
functional analyses of the modified TIMP-2 showed that carbamylation of the alpha
amino group of the NH2-terminal Cys1 of TIMP-2 led to complete loss of the
inhibitory activity. When the reactive-site modified TIMP-2 was added to culture
medium of concanavalin A-stimulated HT1080 cells, the conversion of endogenous
progelatinase A to the intermediate form was partially inhibited, whereas that of
the intermediate form to the mature one was strongly inhibited. The reactive site
modified TIMP-2 also prevented an accumulation of active gelatinase A on the cell
surface. We speculate that occupation of the hemopexin-like domain of gelatinase
A by the reactive site-modified TIMP-2 makes it unable for gelatinase A to be
retained on the cell surface, thus preventing the autocatalytic conversion of the
intermediate form of gelatinase A to its mature form.
PMID- 10187842
TI - Regulation of the transcriptional activity of the peroxisome proliferator
activated receptor alpha by phosphorylation of a ligand-independent trans
activating domain.
AB - The peroxisome proliferator-activated receptors (PPARs) are a subgroup of nuclear
receptors activated by fatty acids and eicosanoids. In addition, they are subject
to phosphorylation by insulin, resulting in the activation of PPARalpha, while
inhibiting PPARgamma under certain conditions. However, it was hitherto unclear
whether the stimulatory effect of insulin on PPARalpha was direct and by which
mechanism it occurs. We now demonstrate that amino acids 1-92 of hPPARalpha
contain an activation function (AF)-1-like domain, which is further activated by
insulin through a pathway involving the mitogen-activated protein kinases p42 and
p44. Further analysis of the amino-terminal region of PPARalpha revealed that the
insulin-induced trans-activation occurs through the phosphorylation of two
mitogen-activated protein kinase sites at positions 12 and 21, both of which are
conserved across evolution. The characterization of a strong AF-1 region in
PPARalpha, stimulating transcription one-fourth as strongly as the viral protein
VP16, is compatible with the marked basal transcriptional activity of this
isoform in transfection experiments. However, it is intriguing that the activity
of this AF-1 region is modulated by the phosphorylation of two serine residues,
both of which must be phosphorylated in order to activate transcription. This is
in contrast to PPARgamma2, which was previously shown to be phosphorylated at a
single site in a motif that is not homologous to the sites now described in
PPARalpha. Although the molecular details involved in the phosphorylation
dependent enhancement of the transcriptional activity of PPARalpha remain to be
elucidated, we demonstrate that the effect of insulin on the AF-1 region of
PPARalpha can be mimicked by the addition of triiodothyronine receptor beta1, a
strong binder of corepressor proteins. In addition, a triiodothyronine receptor
beta1 mutant deficient in interacting with corepressors is unable to activate
PPARalpha. These observations suggest that the AF-1 region of PPARalpha is
partially silenced by corepressor proteins, which might interact in a
phosphorylation-dependent manner.
PMID- 10187843
TI - Unaltered cleavage and secretion of angiotensin-converting enzyme in tumor
necrosis factor-alpha-converting enzyme-deficient mice.
AB - Mammalian angiotensin-converting enzyme (ACE) is one of several biologically
important ectoproteins that exist in both membrane-bound and soluble forms as a
result of a post-translational proteolytic cleavage. It has been suggested that a
common proteolytic system is responsible for the cleavage of a diverse group of
membrane ectoproteins, and tumor necrosis factor-alpha-converting enzyme (TACE),
a recently purified disintegrin-metalloprotease, has been implicated in the
proteolytic cleavage of several cell surface proteins. Mice devoid of TACE have
been developed by gene targeting. Such mice could provide a useful system to
determine if TACE is responsible for the cleavage of other ectoproteins. Cultured
fibroblasts without TACE activity, when transfected with cDNA encoding for the
testicular isozyme of ACE (ACET), synthesized and secreted ACET normally after a
proteolytic cleavage near the C terminus. In addition, similar quantities of the
soluble, C-terminally truncated somatic isozyme of ACE (ACEP) were present in the
serum of wild-type and TACE-deficient mice. These results demonstrate that TACE
is not essential in the generation of soluble ACE under physiological conditions.
Finally, we also report solubilization of ACE-secretase, the enzyme that cleaves
ACE, from mouse ACE89 cells and from rabbit lung. We demonstrate that soluble ACE
secretase from both sources failed to cleave its substrate in solution,
suggesting a requirement for anchoring to the membrane.
PMID- 10187844
TI - Membrane topology of the xenobiotic-exporting subunit, MexB, of the MexA,B-OprM
extrusion pump in Pseudomonas aeruginosa.
AB - The MexA,B-OprM efflux pump assembly of Pseudomonas aeruginosa consists of two
inner membrane proteins and one outer membrane protein. The cytoplasmic membrane
protein, MexB, appears to function as the xenobiotic-exporting subunit, whereas
the MexA and OprM proteins are supposed to function as the membrane fusion
protein and the outer membrane channel protein, respectively. Computer-aided
hydropathy analyses of MexB predicted the presence of up to 17 potential
transmembrane segments. To verify the prediction, we analyzed the membrane
topology of MexB using the alkaline phosphatase gene fusion method. We obtained
the following unique characteristics. MexB bears 12 membrane spanning segments
leaving both the amino and carboxyl termini in the cytoplasmic side of the inner
membrane. Both the first and fourth periplasmic loops had very long hydrophilic
domains containing 311 and 314 amino acid residues, respectively. This fact
suggests that these loops may interact with other pump subunits, such as the
membrane fusion protein MexA and the outer membrane protein OprM. Alignment of
the amino- and the carboxyl-terminal halves of MexB showed a 30% homology and
transmembrane segments 1, 2, 3, 4, 5, and 6 could be overlaid with the segments
7, 8, 9, 10, 11, and 12, respectively. This result suggested that the MexB has a
2-fold repeat that strengthen the experimentally determined topology model. This
paper reports the structure of the pump subunit, MexB, of the MexA,B-OprM efflux
pump assembly. This is the first time to verify the topology of the resistant
nodulation-division efflux pump protein.
PMID- 10187845
TI - Control of expression of one-carbon metabolism genes of Saccharomyces cerevisiae
is mediated by a tetrahydrofolate-responsive protein binding to a glycine
regulatory region including a core 5'-CTTCTT-3' motif.
AB - Expression of yeast genes involved in one-carbon metabolism is controlled by
glycine, by L-methionine, and by nitrogen sources. Here we report a novel control
element containing a core CTTCTT motif mediating the glycine response,
demonstrating that a protein binds this element, that binding is modulated by
tetrahydrofolate, and that folate is required for the in vivo glycine response.
In an heterologous CYC1 promoter the region needed for the glycine response of
GCV2 (encoding the P-subunit of glycine decarboxylase) mediated repression that
was relieved by glycine. It was also responsible for L-methionine control but not
nitrogen repression. GCV1 and GCV3 have an homologous region in their promoters.
The GCV1 region conferred a glycine response on an heterologous promoter acting
as a repressor or activator depending on promoter context. A protein was
identified that bound to the glycine regulatory regions of GCV1 and GCV2 only if
the CTTCTT motif was intact. This protein protected a 17-base pair CATCN7CTTCTT
region of GCV2 that is conserved between GCV1 and GCV2. Protein binding was
increased by tetrahydrofolate, and use of a fol1 deletion mutant indicated the
involvement of a folate in the in vivo glycine response. Tetrahydrofolate or a
derivative may act as a ligand for the transcription factor controlling
expression of one-carbon metabolism genes.
PMID- 10187846
TI - Role of heme in intracellular trafficking of thyroperoxidase and involvement of
H2O2 generated at the apical surface of thyroid cells in autocatalytic covalent
heme binding.
AB - Thyroperoxidase (TPO) is a glycosylated hemoprotein that plays a key role in
thyroid hormone synthesis. We previously showed that in CHO cells expressing
human TPO (hTPO) only 2% of synthesized hTPO reaches the cell surface. Herein, we
investigated the role of heme moiety insertion in the exit of hTPO from the
endoplasmic reticulum. Peroxidase activity at the cell surface and cell surface
expression of hTPO were decreased by approximately 30 and approximately 80%,
respectively, with succinyl acetone, an inhibitor of heme biosynthesis, and were
increased by 20% with holotransferrin and aminolevulinic acid, precursors of heme
biosynthesis. Results were similar with holotransferrin plus aminolevulinic acid
or hemin, but hemin increased cell surface activity more efficiently (+120%)
relative to the control. It had been suggested (DePillis, G., Ozaki, S., Kuo, J.
M., Maltby, D. A., and Ortiz de Montellano, P. R. (1997) J. Biol. Chem. 272, 8857
8960) that covalent attachment of heme to mammalian peroxidases could be an H2O2
dependent autocatalytic processing. In our study, heme associated intracellularly
with hTPO, and we hypothesized that there was insufficient exposure to H2O2 in
Chinese hamster ovary cells before hTPO reached the cell surface. After a 10-min
incubation, 10 microM H2O2 led to a 65% increase in cell surface activity. In
contrast, in thyroid cells, H2O2 was synthesized at the apical cell surface and
allowed covalent attachment of heme. Two-day incubation of primocultures of
thyroid cells with catalase led to a 30% decrease in TPO activity at the cell
surface. In conclusion, we provide compelling evidence for an essential role of
1) heme incorporation in the intracellular trafficking of hTPO and of 2) H2O2
generated at the apical pole of thyroid cells in the autocatalytic covalent heme
binding to the TPO molecule.
PMID- 10187847
TI - Calcium-dependent interaction of S100B with the C-terminal domain of the tumor
suppressor p53.
AB - In vitro, the S100B protein interacts with baculovirus recombinant p53 protein
and protects p53 from thermal denaturation. This effect is isoform-specific and
is not observed with S100A1, S100A6, or calmodulin. Using truncated p53 proteins
in the N-terminal (p53(1-320)) and C-terminal (p53(73-393)) domains, we localized
the S100B-binding region to the C-terminal region of p53. We have confirmed a
calcium-dependent interaction of the S100B with a synthetic peptide corresponding
to the C-terminal region of p53 (residues 319-393 in human p53) using plasmon
resonance experiments on a BIAcore system. In the presence of calcium, the
equilibrium affinity of the S100B for the C-terminal region of p53 immobilized on
the sensor chip was 24 +/- 10 nM. To narrow down the region within p53 involved
in S100B binding, two synthetic peptides, O1(357-381) (residues 357-381 in mouse
p53) and YF-O2(320-346) (residues 320-346 in mouse p53), covering the C-terminal
region of p53 were compared for their interaction with purified S100B. Only YF-O2
peptide interacts with S100B with high affinity. The YF-O2 motif is a critical
determinant for the thermostability of p53 and also corresponds to a domain
responsible for cytoplasmic sequestration of p53. Our results may explain the
rescue of nuclear wild type p53 activities by S100B in fibroblast cell lines
expressing the temperature-sensitive p53val135 mutant at the nonpermissive
temperature.
PMID- 10187848
TI - Interaction of neuronal nitric-oxide synthase and phosphofructokinase-M.
AB - Neurons that express neuronal nitric-oxide synthase (nNOS) are resistant to NO
induced neurotoxicity; however, the mechanism by which these neurons are
protected is not clear. To identify proteins possibly involved in this process,
we performed affinity chromatography with the nNOS PDZ domain, a N-terminal motif
that mediates protein interactions. Using this method to fractionate soluble
tissue extracts, we identified the muscle isoform of phosphofructokinase (PFK-M)
as a protein that binds to nNOS both in brain and skeletal muscle. PFK-M
interacts with the PDZ domain of nNOS, and nNOS-PFK-M binding can be competed by
peptides that bind to the PDZ domain of nNOS. We found that nNOS is significantly
associated with PFK-M in skeletal muscle because nNOS can be immunodepleted from
cytosolic skeletal muscle extracts using an antibody directed against PFK-M. In
brain, nNOS and PFK-M are both enriched in synaptosomes, and specifically, in the
synaptic vesicle fraction, where they can interact. At the cellular level, PFK-M
is enriched in neurons that express nNOS protein. As fructose-1, 6-bisphosphate,
the product of PFK activity, is neuroprotective, the interaction of nNOS and PFK
may contribute to neuroprotection of nNOS positive cells.
PMID- 10187849
TI - Molecular cloning and characterization of hemolymph 3-dehydroecdysone 3beta
reductase from the cotton leafworm, Spodoptera littoralis. A new member of the
third superfamily of oxidoreductases.
AB - The primary product of the prothoracic glands of last instar larvae of Spodoptera
littoralis is 3-dehydroecdysone (3DE). After secretion, 3DE is reduced to
ecdysone by 3DE 3beta-reductase in the hemolymph. We have previously purified and
characterized 3DE 3beta-reductase from the hemolymph of S. littoralis. In this
study, cDNA clones encoding the enzyme were obtained by reverse transcription
polymerase chain reaction, employing primers based on the amino acid sequences,
in conjunction with 5'- and 3'-rapid amplification of cDNA ends. Multiple
polyadenylation signals and AT-rich elements were found in the 3'-untranslated
region, suggesting that this region may have a role in regulation of expression
of the gene. Conceptual translation and amino acid sequence analysis suggest that
3DE 3beta-reductase from S. littoralis is a new member of the third superfamily
of oxidoreductases. Northern analysis shows that 3DE 3beta-reductase mRNA
transcripts are widely distributed, but are differentially expressed, in some
tissues. The developmental profile of the mRNA revealed that the gene encoding
3DE 3beta-reductase is only transcribed in the second half of the last larval
instar and that this fluctuation in expression accounts for the change in the
enzyme activity during the instar. Southern analysis indicates that the 3DE 3beta
reductase is encoded by a single gene, which probably contains at least one
intron.
PMID- 10187850
TI - Phosphorylation-mediated activation and translocation of the cyclic AMP-specific
phosphodiesterase PDE4D3 by cyclic AMP-dependent protein kinase and mitogen
activated protein kinases. A potential mechanism allowing for the coordinated
regulation of PDE4D activity and targeting.
AB - In this study, we describe a novel mechanism by which a protein kinase C (PKC)
mediated activation of the Raf-extracellular signal-regulated kinase kinase (MEK)
extracellular signal-regulated kinase (ERK) cascade regulates the activity and
membrane targeting of members of the cyclic AMP-specific phosphodiesterase D
family (PDE4D). Using a combination of pharmacological and biochemical
approaches, we show that increases in intracellular cAMP cause a protein kinase A
mediated phosphorylation and activation of the two PDE4D variants expressed in
vascular smooth muscle cells, namely PDE4D3 and PDE4D5. In addition, we show that
stimulation of PKC via the associated activation of the Raf-MEK-ERK cascade
results in the phosphorylation and activation of PDE4D3 in these cells.
Furthermore, our studies demonstrate that simultaneous activation of both the
protein kinase A and PKC-Raf-MEK-ERK pathways allows for a coordinated activation
of PDE4D3 and for the translocation of the particulate PDE4D3 to the cytosolic
fraction of these cells. These data are presented and discussed in the context of
the activation of the Raf-MEK-ERK cascade acting to modulate the activation and
subcellular targeting of PDE4D gene products mediated by cAMP.
PMID- 10187851
TI - FAK is the upstream signal protein of the phosphatidylinositol 3-kinase-Akt
survival pathway in hydrogen peroxide-induced apoptosis of a human glioblastoma
cell line.
AB - Protein phosphorylation in a human glioblastoma cell line, T98G, was examined
after exposure to oxidative stress in vitro. Hydrogen peroxide (1 mM) markedly
induced tyrosine phosphorylation of focal adhesion kinase (FAK) and serine
phosphorylation of Akt at 1 h after stimulation. Concommitantly, the association
of FAK with phosphatidylinositide 3'-OH-kinase (PI 3-kinase) was also observed by
the hydrogen peroxide stimulation. When T98G cells were incubated with
wortmannin, a PI 3-kinase inhibitor, both PI 3-kinase activity and
phosphorylation of Akt were inhibited, whereas apoptosis by oxidative stress was
accelerated. Concomitant with apoptosis, elevated level of CPP32 protease
activity (caspase-3) was observed, with decreases in Bcl-2 protein and increases
in Bax protein. These results suggested that in the signal transduction pathway
from FAK to PI 3-kinase, Akt promotes survival. Thus, it became apparent that FAK
is the upstream signal protein of the PI 3-kinase-Akt survival pathway in
hydrogen peroxide-induced apoptosis in T98G cells.
PMID- 10187852
TI - Protein kinase C regulates integrin-induced activation of the extracellular
regulated kinase pathway upstream of Shc.
AB - Adhesion of fibroblasts to extracellular matrices via integrin receptors is
accompanied by extensive cytoskeletal rearrangements and intracellular signaling
events. The protein kinase C (PKC) family of serine/threonine kinases has been
implicated in several integrin-mediated events including focal adhesion
formation, cell spreading, cell migration, and cytoskeletal rearrangements.
However, the mechanism by which PKC regulates integrin function is not known. To
characterize the role of PKC family kinases in mediating integrin-induced
signaling, we monitored the effects of PKC inhibition on fibronectin-induced
signaling events in Cos7 cells using pharmacological and genetic approaches. We
found that inhibition of classical and novel isoforms of PKC by down-regulation
with 12-0-tetradeconoyl-phorbol-13-acetate or overexpression of dominant-negative
mutants of PKC significantly reduced extracellular regulated kinase 2 (Erk2)
activation by fibronectin receptors in Cos7 cells. Furthermore, overexpression of
constitutively active PKCalpha, PKCdelta, or PKCepsilon was sufficient to rescue
12-0-tetradeconoyl-phorbol-13-acetate-mediated down-regulation of Erk2
activation, and all three of these PKC isoforms were activated following
adhesion. PKC was required for maximal activation of mitogen-activated kinase
kinase 1, Raf-1, and Ras, tyrosine phosphorylation of Shc, and Shc association
with Grb2. PKC inhibition does not appear to have a generalized effect on
integrin signaling, because it does not block integrin-induced focal adhesion
kinase or paxillin tyrosine phosphorylation. These results indicate that PKC
activity enhances Erk2 activation in response to fibronectin by stimulating the
Erk/mitogen-activated protein kinase pathway at an early step upstream of Shc.
PMID- 10187853
TI - Cell surface retention sequence binding protein-1 interacts with the v-sis gene
product and platelet-derived growth factor beta-type receptor in simian sarcoma
virus-transformed cells.
AB - The cell surface retention sequence (CRS) binding protein-1 (CRSBP-1) is a newly
identified membrane glycoprotein which is hypothesized to be responsible for cell
surface retention of the oncogene v-sis and c-sis gene products and other
secretory proteins containing CRSs. In simian sarcoma virus-transformed NIH 3T3
cells (SSV-NIH 3T3 cells), a fraction of CRSBP-1 was demonstrated at the cell
surface and underwent internalization/recycling as revealed by cell surface 125I
labeling and its resistance/sensitivity to trypsin digestion. However, the
majority of CRSBP-1 was localized in intracellular compartments as evidenced by
the resistance of most of the 35S-metabolically labeled CRSBP-1 to trypsin
digestion, and by indirect immunofluorescent staining. CRSBP-1 appeared to form
complexes with proteolytically processed forms (generated at and/or after the
trans-Golgi network) of the v-sis gene product and with a approximately 140-kDa
proteolytically cleaved form of the platelet-derived growth factor (PDGF) beta
type receptor, as demonstrated by metabolic labeling and co-immunoprecipitation.
CRSBP-1, like the v-sis gene product and PDGF beta-type receptor, underwent rapid
turnover which was blocked in the presence of 100 microM suramin. In normal and
other transformed NIH 3T3 cells, CRSBP-1 was relatively stable and did not
undergo rapid turnover and internalization/recycling at the cell surface. These
results suggest that in SSV-NIH 3T3 cells, CRSBP-1 interacts with and forms
ternary and binary complexes with the newly synthesized v-sis gene product and
PDGF beta-type receptor at the trans-Golgi network and that the stable binary
(CRSBP-1.v-sis gene product) complex is transported to the cell surface where it
presents the v-sis gene product to unoccupied PDGF beta-type receptors during
internalization/recycling.
PMID- 10187854
TI - SH2-B is required for nerve growth factor-induced neuronal differentiation.
AB - Nerve growth factor (NGF) is essential for the development and survival of
sympathetic and sensory neurons. NGF binds to TrkA, activates the intrinsic
kinase activity of TrkA, and promotes the differentiation of pheochromocytoma
(PC12) cells into sympathetic-like neurons. Several signaling molecules and
pathways are known to be activated by NGF, including phospholipase Cgamma,
phosphatidylinositol-3 kinase, and the mitogen-activated protein kinase cascade.
However, the mechanism of NGF-induced neuronal differentiation remains unclear.
In this study, we examined whether SH2-Bbeta, a recently identified pleckstrin
homology and SH2 domain-containing signaling protein, is a critical signaling
protein for NGF. TrkA bound to glutathione S-transferase fusion proteins
containing SH2-Bbeta, and NGF stimulation dramatically increased that binding. In
contrast, NGF was unable to stimulate the association of TrkA with a glutathione
S-transferase fusion protein containing a mutant SH2-Bbeta(R555E) with a
defective SH2 domain. When overexpressed in PC12 cells, SH2-Bbeta co
immunoprecipitated with TrkA in response to NGF. NGF stimulated tyrosyl
phosphorylation of endogenous SH2-Bbeta as well as exogenously expressed GFP-SH2
Bbeta but not GFP-SH2-Bbeta(R555E). Overexpression of SH2-Bbeta(R555E) blocked
NGF-induced neurite outgrowth of PC12 cells, whereas overexpression of wild type
SH2-Bbeta enhanced NGF-induced neurite outgrowth. Overexpression of either wild
type or mutant SH2-Bbeta(R555E) did not alter tyrosyl phosphorylation of TrkA,
Shc, or phospholipase Cgamma in response to NGF or NGF-induced activation of
ERK1/2, suggesting that SH2-Bbeta may initiate a previously unknown pathway(s)
that is essential for NGF-induced neurite outgrowth. Taken together, these data
indicate that SH2-Bbeta is a novel signaling molecule required for NGF-induced
neuronal differentiation.
PMID- 10187855
TI - Oxidative stress disrupts insulin-induced cellular redistribution of insulin
receptor substrate-1 and phosphatidylinositol 3-kinase in 3T3-L1 adipocytes. A
putative cellular mechanism for impaired protein kinase B activation and GLUT4
translocation.
AB - In a recent study we have demonstrated that 3T3-L1 adipocytes exposed to low
micromolar H2O2 concentrations display impaired insulin stimulated GLUT4
translocation from internal membrane pools to the plasma membrane (Rudich, A.,
Tirosh, A., Potashnik, R., Hemi, R., Kannety, H., and Bashan, N. (1998) Diabetes
47, 1562-1569). In this study we further characterize the cellular mechanisms
responsible for this observation. Two-hour exposure to approximately 25 microM
H2O2 (generated by adding glucose oxidase to the medium) resulted in disruption
of the normal insulin stimulated insulin receptor substrate (IRS)-1 and
phosphatidylinositol (PI) 3-kinase cellular redistribution between the cytosol
and an internal membrane pool (low density microsomal fraction (LDM)). This was
associated with reduced insulin-stimulated IRS-1 and p85-associated PI 3-kinase
activities in the LDM (84 and 96% inhibition, respectively). The effect of this
finding on the downstream insulin signal was demonstrated by a 90% reduction in
insulin stimulated protein kinase B (PKB) serine 473 phosphorylation and impaired
activation of PKBalpha and PKBgamma. Both control and oxidized cells exposed to
heat shock displayed a wortmannin insensitive PKB serine phosphorylation and
activity. These data suggest that activation of PKB and GLUT4 translocation are
insulin signaling events dependent upon a normal insulin induced cellular
compartmentalization of PI 3-kinase and IRS-1, which is oxidative stress
sensitive. These findings represent a novel cellular mechanism for the induction
of insulin resistance in response to changes in the extracellular environment.
PMID- 10187856
TI - Identification of a nucleic acid binding domain in eukaryotic initiation factor
eIFiso4G from wheat.
AB - Higher plants have two complexes that bind the m7G-cap structure of mRNA and
mediate interactions between mRNA and ribosomal subunits, designated eIF4F and
eIFiso4F. Both complexes contain a small subunit that binds the 5'-cap structure
of mRNA, and a large subunit, eIF4G or eIFiso4G, that binds other translation
factors and RNA. Sequence-specific proteases were used to cleave native cap
binding complexes into structural domains, which were purified by affinity
chromatography. We show here that eIFiso4G contains a central protease-resistant
domain that binds specifically to nucleic acids. This domain spans Gln170 to
Glu443 and includes four of the six homology blocks shared by eIFiso4G and eIF4G.
A slightly shorter overlapping sequence, from Gly202 to Lys445, had no nucleic
acid binding activity, indicating that the N-terminal end of the nucleic acid
binding site lies within Gln170 to Arg201. The binding of the central domain and
native eIFiso4F to RNA homopolymers and double- and single-stranded DNAs was
studied. Both molecules had highest affinity for poly(G) and recognized single-
and double-stranded sequences.
PMID- 10187857
TI - CCAAT/enhancer-binding protein delta is a critical regulator of insulin-like
growth factor-I gene transcription in osteoblasts.
AB - Insulin-like growth factor-I (IGF-I) plays a major role in promoting skeletal
growth by stimulating bone cell replication and differentiation. Prostaglandin E2
and other agents that induce cAMP production enhance IGF-I gene transcription in
cultured rat osteoblasts through a DNA element termed HS3D, located in the
proximal part of the major rat IGF-I promoter. We previously determined that
CCAAT/enhancer-binding protein delta (C/EBPdelta) is the key cAMP-stimulated
regulator of IGF-I transcription in these cells and showed that it transactivates
the rat IGF-I promoter through the HS3D site. We now have defined the physical
chemical properties and functional consequences of the interactions between
C/EBPdelta and HS3D. C/EBPdelta, expressed in COS-7 cells or purified as a
recombinant protein from Escherichia coli, bound to HS3D with an affinity at
least equivalent to that of the albumin D-site, a known high affinity C/EBP
binding sequence, and both DNA elements competed equally for C/EBPdelta.
C/EBPdelta bound to HS3D as a dimer, with protein-DNA contact points located on
guanine residues on both DNA strands within and just adjacent to the core C/EBP
half-site, GCAAT, as determined by methylation interference footprinting.
C/EBPdelta also formed protein-protein dimers in the absence of interactions with
its DNA binding site, as indicated by results of glutaraldehyde cross-linking
studies. As established by competition gel-mobility shift experiments, the
conserved HS3D sequence from rat, human, and chicken also bound C/EBPdelta with
similar affinity. We also found that prostaglandin E2-induced expression of
reporter genes containing human IGF-I promoter 1 or four tandem copies of the
human HS3D element fused to a minimal promoter and show that these effects were
enhanced by a co-transfected C/EBPdelta expression plasmid. Taken together, our
results provide evidence that C/EBPdelta is a critical activator of IGF-I gene
transcription in osteoblasts and potentially in other cell types and species.
PMID- 10187858
TI - Identification of the enzyme required for activation of the small ubiquitin-like
protein SUMO-1.
AB - The ubiquitin-like protein SUMO-1 is conjugated to a variety of proteins
including Ran GTPase-activating protein 1 (RanGAP1), IkappaBalpha, and PML. SUMO
1-modified proteins display altered subcellular targeting and/or stability. We
have purified the SUMO-1-activating enzyme from human cells and shown that it
contains two subunits of 38 and 72 kDa. Isolation of cDNAs for each subunit
indicates that they are homologous to ubiquitin-activating enzymes and to the
Saccharomyces cerevisiae enzymes responsible for conjugation of Smt3p and Rub-1p.
In vitro, recombinant SAE1/SAE2 (SUMO-1-activating enzyme) was capable of
catalyzing the ATP-dependent formation of a thioester linkage between SUMO-1 and
SAE2. The addition of the SUMO-1-conjugating enzyme Ubch9 resulted in efficient
transfer of the thioester-linked SUMO-1 from SAE2 to Ubch9. In the presence of
SAE1/SAE2, Ubch9, and ATP, SUMO-1 was efficiently conjugated to the protein
substrate IkappaBalpha. As SAE1/SAE2, Ubch9, SUMO-1, and IkappaBalpha are all
homogeneous, recombinant proteins, it appears that SUMO-1 conjugation of
IkappaBalpha in vitro does not require the equivalent of an E3 ubiquitin protein
ligase activity.
PMID- 10187859
TI - Identification of enhanced serine kinase activity in insulin resistance.
AB - Insulin receptor substrate (IRS) proteins play a crucial role as signaling
molecules in insulin action. Serine phosphorylation of IRS proteins has been
hypothesized as a cause of attenuating insulin signaling. The current study
investigated serine kinase activity toward IRS-1 in several models of insulin
resistance. An in vitro kinase assay was developed that used partially purified
cell lysates as a kinase and glutathione S-transferase fusion proteins that
contained various of IRS-1 fragments as substrates. Elevated serine kinase
activity was detected in Chinese hamster ovary/insulin receptor (IR)/IRS-1 cells
and 3T3-L1 adipocytes chronically treated with insulin, and in liver and muscle
of obese JCR:LA-cp rats. It phosphorylated the 526-859 amino acid region of IRS
1, whereas phosphorylation of the 2-516 and 900-1235 amino acid regions was not
altered. Phosphopeptide mapping of the 526-859 region of IRS-1 showed three major
phosphopeptides (P1, P2, and P3) with different patterns of phosphorylation
depending on the source of serine kinase activity. P1 and P2 were strongly
phosphorylated when the kinase activity was prepared from insulin-resistant
Chinese hamster ovary/IR/IRS-1 cells, weakly phosphorylated by the kinase
activity from insulin-resistant 3T3-L1 adipocytes, and barely phosphorylated when
the extract was derived from insulin-resistant liver. In contrast, P3 was
phosphorylated by the serine kinase activity prepared from all insulin-resistant
cells and tissues of animals. P1 and P2 phosphorylation can be explained by
mitogen-activated protein kinase activity based on the phosphopeptide map
generated by recombinant ERK2. In contrast, mitogen-activated protein kinase
failed to phosphorylate the P3 peptide, suggesting that another serine kinase
regulates this modification of IRS-1 in insulin-resistant state.
PMID- 10187860
TI - Dissociation of apoptosis from proliferation, protein kinase B activation, and
BAD phosphorylation in interleukin-3-mediated phosphoinositide 3-kinase
signaling.
AB - Interleukin-3 (IL-3) acts as both a growth and survival factor for many
hemopoietic cells. IL-3 treatment of responsive cells leads to the rapid and
transient activation of Class IA phosphoinositide-3-kinases (PI3Ks) and the
serine/threonine kinase Akt/protein kinase B (PKB) and phosphorylation of BAD.
Each of these molecules has been implicated in anti-apoptotic signaling in a wide
range of cells. Using regulated expression of dominant-negative p85 (Deltap85) in
stably transfected IL-3-dependent BaF/3 cells, we have specifically investigated
the role of class IA PI3K in IL-3 signaling. The major functional consequence of
Deltap85 expression in these cells is a highly reproducible, dramatic reduction
in IL-3-induced proliferation. Expression of Deltap85 reduces IL-3-induced PKB
phosphorylation and activation and phosphorylation of BAD dramatically, to levels
seen in unstimulated cells. Despite these reductions, the levels of apoptosis
observed in the same cells are very low and do not account for the reduction in
IL-3-dependent proliferation we observe. These results show that Deltap85
inhibits both PKB activity and BAD phosphorylation without significantly
affecting levels of apoptosis, suggesting that there are targets other than PKB
and BAD that can transmit survival signals in these cells. Our data indicate that
the prime target for PI3K action in IL-3 signaling is at the level of regulation
of proliferation.
PMID- 10187861
TI - Functional interactions of transforming growth factor beta-activated kinase 1
with IkappaB kinases to stimulate NF-kappaB activation.
AB - Several mitogen-activated protein kinase kinase kinases play critical roles in
nuclear factor-kappaB (NF-kappaB) activation. We recently reported that the
overexpression of transforming growth factor-beta-activated kinase 1 (TAK1), a
member of the mitogen-activated protein kinase kinase kinase family, together
with its activator TAK1-binding protein 1 (TAB1) stimulates NF-kappaB activation.
Here we investigated the molecular mechanism of TAK1-induced NF-kappaB
activation. Dominant negative mutants of IkappaB kinase (IKK) alpha and IKKbeta
inhibited TAK1-induced NF-kappaB activation. TAK1 activated IKKalpha and IKKbeta
in the presence of TAB1. IKKalpha and IKKbeta were coimmunoprecipitated with TAK1
in the absence of TAB1. TAB1-induced TAK1 activation promoted the dissociation of
active forms of IKKalpha and IKKbeta from active TAK1, whereas the IKK mutants
remained to interact with active TAK1. Furthermore, tumor necrosis factor-alpha
activated endogenous TAK1, and the kinase-negative TAK1 acted as a dominant
negative inhibitor against tumor necrosis factor-alpha-induced NF-kappaB
activation. These results demonstrated a novel signaling pathway to NF-kappaB
activation through TAK1 in which TAK1 may act as a regulatory kinase of IKKs.
PMID- 10187862
TI - Heterogeneity and differential expression under hypoxia of two-domain hemoglobin
chains in the water flea, Daphnia magna.
AB - Hemoglobin (Hb) purified from the water flea, Daphnia magna, reared under hypoxia
was analyzed by two-dimensional gel electrophoresis. The Hb was shown to be
composed of six major subunit chain species (designated as DHbA to DHbF). The NH2
terminal amino acid sequences of DHbA, DHbB, DHbC, and DHbF are different from
one another, indicating that at least four Hb genes are present in D. magna. The
NH2-terminal amino acid sequences of DHbD and DHbE are the same as those of DHbA
and DHbB, respectively. The six Hb chains were also found in the animal reared
under normoxia in small amounts and with altered composition; the extent of
decrease under normoxia was higher in the amounts of DHbC, DHbD, and DHbF than
those of others. These results indicate that the Hb genes are differentially
regulated by the ambient oxygen concentration. Four Hb genes constituting a
cluster in the order, dhb4, dhb3, dhb1, and dhb2, were found on the chromosome of
D. magna. The complete nucleotide sequences of the dhb1, dhb2, and dhb3 genes and
their cDNAs showed that the genes have a seven-exon, six-intron structure. The
structure consists of an intron separating an exon encoding a secretory signal
sequence, two large repeated regions of a three-exon, two-intron structure that
encode each a domain containing a heme-binding site, and an intron bridging the
two repeated regions. The deduced amino acid sequences of the gene products
showed higher than 79% identity to one another and showed unique features
conserved in D. magna Hb chains. The analysis also suggested that DHbB (or DHbE),
DHbF, and DHbC are encoded by the dhb1, dhb2, and dhb3 genes, respectively.
PMID- 10187863
TI - Ceramide generation in nitric oxide-induced apoptosis. Activation of magnesium
dependent neutral sphingomyelinase via caspase-3.
AB - Sodium nitroprusside (SNP), a NO donor, has been recognized as an inducer of
apoptosis in various cell lines. Here, we demonstrated the intracellular
formation of ceramide, a lipid signal mediator, in SNP-induced apoptosis in human
leukemia HL-60 cells and investigated the mechanisms of ceramide generation. The
levels of intracellular ceramide increased to, at most, 160% of the control level
in a time- and dose-dependent manner when the cells were treated with 1 mM SNP.
SNP also decreased the sphingomyelin level to approximately 70% of the control
level and increased magnesium-dependent neutral sphingomyelinase (N-SMase)
activity to 160% of the control activity 2 h after treatment. Neither acid SMase
nor magnesium-independent N-SMase was affected by SNP. Caspases are thought to be
key enzymes in apoptotic cell death. Acetyl-Asp-Glu-Val-Asp-aldehyde, a synthetic
tetrapeptide inhibitor of caspases, inhibited magnesiumdependent N-SMase,
ceramide generation, and apoptosis. Moreover, recombinant purified caspase-3
increased magnesium-dependent N-SMase in a cell-free system. These results
suggest that the findings that SNP increased ceramide generation and magnesium
dependent N-SMase activity via caspase-3 are interesting to future study to
determine the relation between caspases and sphingolipid metabolites in NO
mediated signaling.
PMID- 10187864
TI - Cloning, characterization, and chromosomal location of a novel human K+-Cl-
cotransporter.
AB - Differential display polymerase chain reaction has been used to isolate genes
regulated in vascular endothelial cells by the angiogenic factor vascular
endothelial cell growth factor (VEGF). Analysis of one of the bands consistently
up-regulated by VEGF led us to the identification of a cDNA from a human
umbilical vein endothelial cell library that is 77% identical to the human K+-Cl-
cotransporter1 (KCC1). We have referred to the predicted protein as K+-Cl-
cotransporter 3 (KCC3). Hydrophobicity analysis of the KCC3 amino acid sequence
showed an almost identical pattern to KCC1, suggesting 12 membrane-spanning
segments, a large extracellular loop with potential N-glycosylation sites, and
cytoplasmic N- and C-terminal regions. The KCC3 mRNA was highly expressed in
brain, heart, skeletal muscle, and kidney, showing a distinct pattern and size
from KCC1 and KCC2. The KCC3 mRNA level in endothelial cells increased on
treatment with VEGF and decreased with the proinflammatory cytokine tumor
necrosis factor alpha, whereas KCC1 mRNA levels remained unchanged. Stable
overexpression of KCC3 cDNA in HEK293 cells produced a glycoprotein of
approximately 150 kDa, which was reduced to 120 kDa by glycosidase digestion. An
increased initial uptake rate of 86Rb was seen in clones with high KCC3
expression, which was dependent on extracellular Cl- but not Na+ and was
inhibitable by the loop diuretic agent furosemide. The KCC3 genomic localization
was shown to be 15q13 by fluorescence in situ hybridization. Radiation hybrid
analysis placed KCC3 within an area associated with juvenile myoclonic epilepsy.
These results suggest KCC3 is a new member of the KCC family that is under
distinct regulation from KCC1.
PMID- 10187866
TI - Stroke units in their natural habitat: can results of randomized trials be
reproduced in routine clinical practice? Riks-Stroke Collaboration.
AB - BACKGROUND AND PURPOSE: Meta-analyses of randomized controlled trials of acute
stroke care have shown care in stroke units (SUs) to be superior to that in
conventional general medical, neurological, or geriatric wards, with reductions
in early case fatality, functional outcome, and the need for long-term
institutionalization. This study examined whether these results can be reproduced
in clinical practice. METHODS: A multicenter observational study of procedures
and outcomes in acute stroke patients admitted to designated SUs or general
medical or neurological wards (GWs), the study included patients of all ages with
acute stroke excluding those with subarachnoid hemorrhage, who were entered into
the Riks-Stroke (Swedish national quality assessment) database during 1996 (14
308 patients in 80 hospitals). RESULTS: Patients admitted to SUs who had lived
independently and who were fully conscious on admission to the hospital had a
lower case fatality than those cared for in GWs (relative risk [RR] for death,
0.87; 95% confidence interval [CI], 0.79 to 0.96) and at 3 months (RR, 0.91; 95%
CI, 0.85 to 0.98). A greater proportion of patients cared for in an SU could be
discharged home (RR, 1.06; 95% CI, 1.03 to 1.10), and fewer were in long-term
institutional care 3 months after the stroke (RR, 0.94; 95% CI, 0.89 to 0.99). No
difference was seen in outcome in patients cared for in SUs or GWs if they had
impaired consciousness on admission. CONCLUSIONS: The improvement in outcomes
after stroke care in SUs compared with care in GWs can be reproduced in the
routine clinical setting, but the magnitude of the benefit appears smaller than
that reported from meta-analyses.
PMID- 10187867
TI - Sexual functioning among stroke patients and their spouses.
AB - BACKGROUND AND PURPOSE: The aim of this study was to assess effects of stroke on
sexual functioning of stroke patients and their spouses and to study the
associations of clinical and psychosocial factors with poststroke changes in
sexual functions. METHODS: One hundred ninety-two stroke patients and 94 spouses
participating in stroke adjustment courses sponsored by the Finnish Stroke and
Aphasia Federation completed a self-administered questionnaire concerning their
prestroke and poststroke sexual functions and habits. The main outcome measures
were (1) libido, (2) coital frequency, (3) sexual arousal, including erectile and
orgastic ability and vaginal lubrication, and (4) sexual satisfaction. RESULTS: A
majority of the stroke patients reported a marked decline in all the measured
sexual functions, ie, libido, coital frequency, erectile and orgastic ability,
and vaginal lubrication, as well as in their sexual satisfaction. The most
important explanatory factors for these changes were the general attitude toward
sexuality (odds ratio [OR] range, 7.4 to 21.9; logistic regression analysis),
fear of impotence (OR, 6.1), inability to discuss sexuality (OR range, 6.8 to
18.5), unwillingness to participate in sexual activity (OR range, 3.1 to 5. 4),
and the degree of functional disability (OR range, 3.2 to 5.0). The spouses also
reported a significant decline in their libido, sexual activity, and sexual
satisfaction as a consequence of stroke. CONCLUSIONS: Sexual dysfunction and
dissatisfaction with sexual life are common in both male and female stroke
patients and in their spouses. Psychological and social factors seem to exert a
strong impact on sexual functioning and the quality of sexual life after stroke.
PMID- 10187868
TI - Community education for stroke awareness: An efficacy study.
AB - BACKGROUND AND PURPOSE: This study examined the effectiveness of a slide/audio
community education program aimed at increasing knowledge of stroke risk factors,
stroke warning signs, and action needed when stroke warning signs occur. The
program targets audiences at higher risk for stroke, especially individuals who
are black or >50 years of age. METHODS: Subjects were 657 adults living in the
community or in senior independent-living settings. The study examined the
effectiveness of the program when presented alone and when accompanied by
discussion (facilitation) led by a trained individual. Knowledge of stroke risk
factors and warning signs was assessed using parallel pretests and posttests
developed and validated specifically for the study. RESULTS: ANCOVA indicated
that neither pretesting nor facilitation had a significant effect on posttest
measures of knowledge. Paired t tests of groups receiving both the pretest and
posttest demonstrated significant increase in knowledge (mean increase, 10.87%;
P<0.001). ANCOVA indicated that these gains in knowledge were similar across
subjects of different sex, race, age, and educational level. No significant
differences could be ascribed to facilitation. CONCLUSIONS: The data indicate
that the slide/audio program is effective in increasing knowledge of stroke risk
factors, warning signs, and necessary action in subjects of varying ages, races,
and education. Pretesting and facilitation did not significantly affect the short
term acquisition of information. The slide/audio program appears to offer a
short, easily used educational experience for diverse communities, whether as a
stand-alone program or with facilitated discussion.
PMID- 10187869
TI - Predictors of acute hospital costs for treatment of ischemic stroke in an
academic center.
AB - BACKGROUND AND PURPOSE: We sought to determine predictors of acute hospital costs
in patients presenting with acute ischemic stroke to an academic center using a
stroke management team to coordinate care. METHODS: Demographic and clinical data
were prospectively collected on 191 patients consecutively admitted with acute
ischemic stroke. Patients were classified by insurance status, premorbid modified
Rankin scale, stroke location, stroke severity (National Institutes of Health
Stroke Scale score), and presence of comorbidities. Detailed hospital charge data
were converted to cost by application of department-specific cost-to-charge
ratios. Physician's fees were not included. A stepwise multiple regression
analysis was computed to determine the predictors of total hospital cost.
RESULTS: Median length of stay was 6 days (range, 1 to 63 days), and mortality
was 3%. Median hospital cost per discharge was $4408 (range, $1199 to $59 799).
Fifty percent of costs were for room charges, 19% for stroke evaluation, 21% for
medical management, and 7% for acute rehabilitation therapies. Sixteen percent
were admitted to an intensive care unit. Length of stay accounted for 43% of the
variance in total cost. Other independent predictors of cost included stroke
severity, heparin treatment, atrial fibrillation, male sex, ischemic cardiac
disease, and premorbid functional status. CONCLUSIONS: We conclude that the major
predictors of acute hospital costs of stroke in this environment are length of
stay, stroke severity, cardiac disease, male sex, and use of heparin. Room
charges accounted for the majority of costs, and attempts to reduce the cost of
stroke evaluation would be of marginal value. Efforts to reduce acute costs
should be monitored for potential cost shifting or a negative impact on quality
of care.
PMID- 10187870
TI - Economic consequences of early inpatient discharge to community-based
rehabilitation for stroke in an inner-London teaching hospital.
AB - BACKGROUND AND PURPOSE: In an inner-London teaching hospital, a randomized trial
of "conventional" care versus early discharge to community-based therapy found no
significant differences in clinical outcomes between patient groups. This report
examines the economic consequences of the alternative strategies. METHODS: One
hundred sixty-seven patients received the early discharge package, and 164
received conventional care. Patient utilization of health and social services was
recorded over a 12-month period, and cost was determined using data from provider
departments and other published sources. RESULTS: Inpatient stay after
randomization was 12 days (intervention group) versus 18 days (controls)
(P=0.0001). Average units of therapy per patient were as follows: physiotherapy,
22.4 (early discharge) versus 15.0 (conventional) (P=0.0006); occupational
therapy, 29.0 versus 23.8 (P=0.002); speech therapy, 13. 7 versus 5.8 (P=0.0001).
The early discharge group had more annual hospital physician contacts (P=0.015)
and general practitioner clinic visits (P=0.019) but fewer incidences of day
hospital attendance (P=0.04). Other differences in utilization were
nonsignificant. Average annual costs per patient were pound sterling 6800 (early
discharge) and pound sterling 7432 (conventional). The early discharge group had
lower inpatient costs per patient (pound sterling 4862 [71% of total cost] versus
pound sterling 6343 [85%] for controls) but higher non-inpatient costs (pound
sterling 1938 [29%] versus pound sterling 1089 [15%]). Further analysis
demonstrated that early discharge is unlikely to lead to financial savings; its
main benefit is to release capacity for an expansion in stroke caseload.
CONCLUSIONS: Overall results of this trial indicate that early discharge to
community rehabilitation for stroke is cost-effective. It may provide a means of
addressing the predicted increase in need for stroke care within existing
hospital capacity.
PMID- 10187871
TI - Stroke incidence and survival among middle-aged adults: 9-year follow-up of the
Atherosclerosis Risk in Communities (ARIC) cohort.
AB - BACKGROUND AND PURPOSE: Although stroke mortality rates in the United States are
well documented, assessment of incidence rates and case fatality are less well
studied. METHODS: A cohort of 15 792 men and women aged 45 to 64 years from a
population sample of households in 4 US communities was followed from 1987 to
1995, an average of 7. 2 years. Incident strokes were identified through annual
phone contacts and hospital record searching and were then validated. RESULTS: Of
the 267 incident definite or probable strokes, 83% (n=221) were categorized as
ischemic strokes, 10% (n=27) were intracerebral hemorrhages, and 7% (n=19) were
subarachnoid hemorrhages. The age-adjusted incidence rate (per 1000 person-years)
of total strokes was highest among black men (4.44), followed by black women
(3.10), white men (1.78), and white women (1.24). The black versus white age
adjusted rate ratio (RR) for ischemic stroke was 2.41 (95% CI, 1.85 to 3.15),
which was attenuated to 1.38 (95% CI, 1.01 to 1.89) after adjustment for baseline
hypertension, diabetes, education level, smoking status, and prevalent coronary
heart disease. There was a tendency for the adjusted case fatality rates to be
higher among blacks and men, although none of the case fatality comparisons
across sex or race was statistically significant. CONCLUSIONS: After accounting
for established baseline risk factors, blacks still had a 38% greater risk of
incident ischemic stroke compared with whites. Identification of new individual
and community-level risk factors accounting for the elevated incidence of stroke
requires further investigation and incorporation into intervention planning.
PMID- 10187872
TI - Swallowing function after stroke: prognosis and prognostic factors at 6 months.
AB - BACKGROUND AND PURPOSE: Swallowing dysfunction (dysphagia) is common and
disabling after acute stroke, but its impact on long-term prognosis for potential
complications and the recovery from swallowing dysfunction remain uncertain. We
aimed to prospectively study the prognosis of swallowing function over the first
6 months after acute stroke and to identify the important independent clinical
and videofluoroscopic prognostic factors at baseline that are associated with an
increased risk of swallowing dysfunction and complications. METHODS: We
prospectively assembled an inception cohort of 128 hospital-referred patients
with acute first stroke. We assessed swallowing function clinically and
videofluoroscopically, within a median of 3 and 10 days, respectively, of stroke
onset, using standardized methods and diagnostic criteria. All patients were
followed up prospectively for 6 months for the occurrence of death, recurrent
stroke, chest infection, recovery of swallowing function, and return to normal
diet. RESULTS: At presentation, a swallowing abnormality was detected clinically
in 65 patients (51%; 95% CI, 42% to 60%) and videofluoroscopically in 82 patients
(64%; 95% CI, 55% to 72%). During the subsequent 6 months, 26 patients (20%; 95%
CI, 14% to 28%) suffered a chest infection. At 6 months after stroke, 97 of the
112 survivors (87%; 95% CI, 79% to 92%) had returned to their prestroke diet.
Clinical evidence of a swallowing abnormality was present in 56 patients (50%;
95% CI, 40% to 60%). Videofluoroscopy was performed at 6 months in 67 patients
who had a swallowing abnormality at baseline; it showed penetration of the false
cords in 34 patients and aspiration in another 17. The single independent
baseline predictor of chest infection during the 6-month follow-up period was a
delayed or absent swallowing reflex (detected by videofluoroscopy). The single
independent predictor of failure to return to normal diet was delayed oral
transit (detected by videofluoroscopy). Independent predictors of the combined
outcome event of swallowing impairment, chest infection, or aspiration at 6
months were videofluoroscopic evidence of delayed oral transit and penetration of
contrast into the laryngeal vestibule, age >70 years, and male sex. CONCLUSIONS:
Swallowing function should be assessed in all acute stroke patients because
swallowing dysfunction is common, it persists in many patients, and complications
frequently arise. The assessment of swallowing function should be both clinical
and videofluoroscopic. The clinical and videofluoroscopic features at
presentation that are important predictors of subsequent swallowing abnormalities
and complications are videofluoroscopic evidence of delayed oral transit, a
delayed or absent swallow reflex, and penetration. These findings require
validation in other studies.
PMID- 10187873
TI - Plasticity of language-related brain function during recovery from stroke.
AB - BACKGROUND AND PURPOSE: This study was undertaken to correlate functional
recovery from aphasia after acute stroke with the temporal evolution of the
anatomic, physiological, and functional changes as measured by MRI. METHODS:
Blood oxygenation level-dependent contrast and echo-planar MRI were used to map
language comprehension in 6 normal adults and in 2 adult patients during recovery
from acute stroke presenting with aphasia. Perfusion, diffusion, sodium, and
conventional anatomic MRI were used to follow physiological and structural
changes. RESULTS: The normal activation pattern for language comprehension showed
activation predominately in left-sided Wernicke's and Broca's areas, with
laterality ratios of 0.8 and 0.3, respectively. Recovery of the patient confirmed
as having a completed stroke affecting Broca's area occurred rapidly with a shift
of activation to the homologous region in the right hemisphere within 3 days,
with continued rightward lateralization over 6 months. In the second patient, in
whom mapping was performed fortuitously before stroke, recovery of a Wernicke's
aphasia showed a similar increasing rightward shift in activation recruitment
over 9 months after the event. CONCLUSIONS: Recovery of aphasia in adults can
occur rapidly and is concomitant with an activation pattern that changes from
left to a homologous right hemispheric pattern. Such recovery occurs even when
the stroke evolves to completion. Such plasticity must be considered when
evaluating stroke interventions based on behavioral and neurological
measurements.
PMID- 10187874
TI - Hemiosteoporosis after severe stroke, independent of changes in body composition
and weight.
AB - BACKGROUND AND PURPOSE: Fractures are a serious complication after stroke, and
the risk of hip fractures among stroke patients is increased 2 to 4 times versus
a reference population. Fractures after stroke are probably caused by the
development of hemiosteoporosis and the high incidence of accidental falls. The
aim of this study was to investigate the development of hemiosteoporosis in
relation to other changes in body composition during the first year after severe
stroke. METHODS: The study included 24 patients with extensive paresis after
stroke. Bone mineral content (BMC) and fat and lean mass were assessed 1, 4, 7,
and 12 months after stroke onset by a dual-energy x-ray absorptiometer. RESULTS:
The loss of total body BMC was significant during the first year after stroke (
1.6%; P<0.05), but there were no significant changes in total lean or fat mass.
At inclusion, there were no significant differences between sides in lean or fat
mass or BMC, but during follow-up, BMC of the affected side decreased
significantly compared with the same side at inclusion (-7.5%; P<0.01). Side
differences in fat mass became significant between legs (9.3%; P<0.001) and whole
sides (4. 8%; P<0.01). There were only minor side changes in lean mass. Loss of
BMC was independent of weight changes. CONCLUSIONS: During the first year after
severe stroke, patients developed pronounced hemiosteoporosis. This was not
associated with general changes in lean or fat mass. The development of
hemiosteoporosis was independent of weight changes after stroke.
PMID- 10187875
TI - Hemorrhage after an acute ischemic stroke.MAST-I Collaborative Group.
AB - BACKGROUND AND PURPOSE: Hemorrhagic transformation is frequently seen on CT scans
obtained in the subacute phase of ischemic stroke. Its prognostic value is
controversial. METHODS: We analyzed 554 patients with acute ischemic stroke
enrolled in the Multicenter Acute Stroke Trial-Italy (MAST-I) study in whom a
second CT scan was performed on day 5. Presence of 1) intraparenchymal
hemorrhages (hematoma or hemorrhagic infarction), 2) extraparenchymal bleeding
(intraventricular or subarachnoid) and 3) cerebral edema (shift of midline
structure, sulcal effacement or ventricular compression) alone or in association
were evaluated. Death or disability at 6 months were considered as "unfavorable
outcome." RESULTS: Patients who developed intraparenchymal hemorrhages,
extraparenchymal bleeding, or cerebral edema had unfavorable outcome (83%, 100%,
and 80%, respectively), but multivariate analysis demonstrated that only
extraparenchymal bleeding (collinearity) and cerebral edema (OR=6.8; 95% CI, 4.5
to 10.4) were significant independent prognostic findings. Unfavorable outcome
correlated with size of intraparenchymal hemorrhage (chi2 for trend=30.5,
P<0.0001). Nevertheless, when a large hematoma was present the negative effect
was mostly due to concomitant extraparenchymal bleeding (chi2=51.6, P<0.0001),
and when hemorrhagic infarction was detected the negative effect was mostly
explained by the association with cerebral edema (chi2=36.6, P<0.0001).
CONCLUSIONS: Extraparenchymal bleeding and cerebral edema are the main prognostic
CT scan findings in the subacute phase of ischemic stroke. Stroke patients with a
high risk for developing these 2 types of brain damage should be identified.
Measures to prevent and adequately treat their development should be implemented.
PMID- 10187876
TI - A standardized MRI stroke protocol: comparison with CT in hyperacute
intracerebral hemorrhage.
AB - BACKGROUND AND PURPOSE: Diagnostic imaging in hyperacute ischemic stroke has been
revolutionized by the introduction of diffusion- and perfusion-weighted MRI (DWI
and PWI). CT, however, is still needed to exclude intracerebral hemorrhage (ICH).
The purpose of our study was to determine the diagnostic accuracy of a
standardized, multimodal MRI (mMRI) stroke protocol in the qualitative and
quantitative assessment of hyperacute ICH (<6 hours). METHODS: We investigated 9
patients with hyperacute ICH with CT followed immediately by a standardized mMRI
stroke protocol (DWI, PWI [T2*-WI], FLAIR, T2-WI, and MRA). The time interval
between MRI and symptom onset ranged from 3 hours to 5 hours 45 minutes. We
analyzed and compared the size of the hematoma on CT and all mMRI images by
semiautomatic volumetry. RESULTS: ICH was unambiguously identified on the basis
of all mMRI sequences. With increasing susceptibility effect (T2*-WI), the ICH,
appearing as an area of hyperintensity with central signal loss, became
qualitatively most evident. Regarding quantitation, T2*-WI overestimated (median
and mean difference, 18.9%/17.8%; SD final sigma=24.4%) and DWI correlated best
(median and mean difference, 3.97%/-4.36%; SD final sigma=37. 42%) with hematoma
size on CT. CONCLUSIONS: Multimodal stroke MRI is as reliable as CT in the
assessment of hyperacute ICH. Therefore, additional CT is no longer necessary to
rule out ICH in hyperacute stroke. The use of mMRI alone in the diagnostic workup
of a hyperacute stroke patient saves time and costs while rendering all the
critical information needed to initiate an optimal treatment.
PMID- 10187877
TI - Association of hyperdense middle cerebral artery sign with clinical outcome in
patients treated with tissue plasminogen activator.
AB - BACKGROUND AND PURPOSE: The hyperdense middle cerebral artery sign (HMCAS) is a
marker of thrombus in the middle cerebral artery. The aim of our study was to
find out the frequency of the HMCAS, its association with initial neurological
severity and early parenchymal ischemic changes on CT, its relevance to clinical
outcome, and the efficacy of intravenous recombinant tissue plasminogen activator
(rtPA) in patients with the HMCAS. METHODS: Secondary analysis of the data from
620 patients who received either rtPA or placebo in the European Cooperative
Acute Stroke Study I (ECASS I), a double-blind, randomized, multicenter trial.
The baseline CT scans were obtained within 6 hours from the onset of symptoms.
Functional and neurological outcomes were assessed using the modified Rankin
Scale and the Scandinavian Stroke Scale at day 90. RESULTS: We found an HMCAS in
107 patients(17.7%). The initial neurological deficit was more severe in patients
with the HMCAS than in those lacking this sign (P<0.0001). Early cerebral edema
and mass effect were also more common in patients with the HMCAS (P<0.0001). The
HMCAS was related to the risk of poor functional outcome (grade of 3 to 6 on the
modified Rankin Scale) on univariate analysis: 90 patients (84%) with the HMCAS
and 310 patients (62%) lacking this sign were dependent or dead at day 90
(P<0.0001). However, this association was no longer significant in a logistic
model accounting for the effect of age, sex, treatment with rtPA, initial
severity of neurological deficit and early parenchymal ischemic changes on CT.
Patients with the HMCAS who were given rtPA had better neurological recovery than
those who received placebo (P=0.0297). CONCLUSIONS: The HMCAS is associated with
severe brain ischemia and poor functional outcome. However, it has no significant
independent prognostic value when accounting for the effect of initial severity
of neurological deficit and of early parenchymal ischemic changes on CT. Patients
with the HMCAS may benefit from intravenous rtPA.
PMID- 10187878
TI - Confusional state in stroke: relation to preexisting dementia, patient
characteristics, and outcome.
AB - BACKGROUND AND PURPOSE: Acute confusional state (ACS) is frequent in hospitalized
stroke patients. We previously showed that 16% of patients admitted for a stroke
have preexisting dementia. The extent to which preexisting cognitive decline is
associated with a risk of ACS at the acute stage of stroke remains to be
systematically examined. The aim of this study was to evaluate the prevalence of
ACS in acute stroke patients, to study the influence of preexisting cognitive
decline and other patient characteristics, and to evaluate the influence of ACS
on outcome. METHODS: We diagnosed ACS using DSM-IV criteria and the Delirium
Rating Scale with a cutoff of 10 in 202 consecutive stroke patients aged 40 years
or older (median age, 75 years; range, 42 to 101 years). Cognitive functioning
before stroke was assessed with the Informant Questionnaire on Cognitive Decline
in the Elderly. RESULTS: Forty-nine stroke patients (24.3%; 95% CI, 18.3% to
30.2%) had an ACS during hospitalization. Using logistic regression analysis, we
found preexisting cognitive decline (P=0.006) and metabolic or infectious
disorders (P=0.008) to be independent predictors of ACS. Functional, but not
vital, prognosis was worse in patients with ACS at discharge and 6 months after
stroke. CONCLUSIONS: ACS occurs in one fourth of stroke patients older than 40
years. Its occurrence requires inquiry for a preexisting cognitive decline, which
usually remains unrecognized in the absence of a systematic evaluation.
PMID- 10187879
TI - Myocardial injury and left ventricular performance after subarachnoid hemorrhage.
AB - BACKGROUND AND PURPOSE: Electrocardiographic abnormalities and elevations of the
creatine kinase myocardial isoenzyme (CK-MB) occur frequently after subarachnoid
hemorrhage. In some patients, a reversible and presumably neurogenic form of left
ventricular dysfunction is demonstrated by echocardiography. It is not known
whether cardiac injury of this type adversely affects cardiovascular hemodynamic
performance. METHODS: We retrospectively studied 72 patients admitted to our
neuro-ICU for aneurysmal subarachnoid hemorrhage over a 2.5-year period. We
selected patients who met the following criteria: (1) CK-MB levels measured
within 3 days of onset, (2) pulmonary artery catheter placed, (3) echocardiogram
performed, and (4) no history of preexisting cardiac disease. Hemodynamic
profiles were recorded on the day after surgery (n=67) or on the day of
echocardiography (n=5) if surgery was not performed (mean, 3. 3+/-1.7 days after
onset). The severity of cardiac injury was classified as none (peak CK-MB <1%,
n=36), mild (peak CK-MB 1% to 2%, n=21), moderate (peak CK-MB >2%, n=6), or
severe (abnormal left ventricular wall motion, n=9). RESULTS: Abnormal left
ventricular wall motion occurred exclusively in patients with peak CK-MB levels
>2% (P<0.0001), poor neurological grade (P=0.002), and female sex (P=0.02). Left
ventricular stroke volume index and stroke work index were elevated above the
normal range in patients with peak CK-MB levels <1% and fell progressively as the
severity of cardiac injury increased, with mean values for patients with abnormal
wall motion below normal (both P<0.0001 by ANOVA). Cardiac index followed a
similar trend, but the effect was less pronounced (P<0.0001). Using forward
stepwise multiple logistic regression, we found that thick subarachnoid clot on
the admission CT scan (odds ratio, 1.9; 95% confidence interval [95% CI], 1.0 to
3.4; P=0.04) and depressed cardiac index (odds ratio, 2.1; 95% CI, 1.0 to 4.1;
P=0.04) were independent predictors of symptomatic vasospasm. CONCLUSIONS:
Myocardial enzyme release and echocardiographic wall motion abnormalities are
associated with impaired left ventricular performance after subarachnoid
hemorrhage. In severely affected patients, reduction of cardiac output from
normally elevated levels may increase the risk of cerebral ischemia related to
vasospasm.
PMID- 10187880
TI - Extracorporeal rheopheresis in the treatment of acute ischemic stroke: A
randomized pilot study.
AB - BACKGROUND AND PURPOSE: Extracorporeal rheopheresis is a safe method to optimize
hemorheology. Our aim was to determine whether treatment with extracorporeal
rheopheresis in patients with acute ischemic hemispheric stroke improves cerebral
perfusion as assessed with serial 99mTc-ethyl-cysteinate-dimer single-photon
emission CT (99mTc-ECD SPECT). We also investigated how clinical outcome is
associated with treatment and imaging results. METHODS: Thirty-three patients
(mean age, 64+/-10 years) with acute ischemic hemispheric stroke were included in
a prospective, randomized, parallel group pilot study. First treatment with or
without extracorporeal rheopheresis took place within 12 hours after the onset of
symptoms and was repeated 3 times at intervals of 24 hours. Hemorheological
parameters were measured before and after each session. Each patient underwent
99mTc-ECD SPECT immediately before treatment, 6 to 8 hours after treatment, and
after 5 days. A semiquantitative SPECT graded scale was used to measure depth and
extent of activity deficits and thus to quantify the perfusion deficit. RESULTS:
Seventeen patients were actively treated with extracorporeal rheopheresis, and 16
patients did not receive extracorporeal rheopheresis. After 3 months, no
differences were found in the functional or neurological outcome. Despite a
rapid, sustained decrease of plasma viscosity and erythrocyte aggregation in the
rheopheresis group, there was no significant difference in the SPECT graded scale
after therapy between the 2 groups. Patients with early reperfusion (decrease in
the SPECT graded scale >25% 6 to 8 hours after therapy compared with the baseline
examination) experienced a better functional outcome (Modified Rankin Scale)
after 3 months compared with patients without reperfusion (P=0.04). CONCLUSIONS:
Since quantitative flow mapping and clinical follow-up did not reveal any
differences between patients who were treated with extracorporeal rheopheresis
and controls, it appears very unlikely that extracorporeal rheopheresis enhances
reperfusion after acute cerebral ischemia.
PMID- 10187881
TI - Glucose potassium insulin infusions in the treatment of acute stroke patients
with mild to moderate hyperglycemia: the Glucose Insulin in Stroke Trial (GIST).
AB - BACKGROUND AND PURPOSE: Hyperglycemia following acute stroke is strongly
associated with subsequent mortality and impaired neurological recovery, but it
is unknown whether maintenance of euglycemia in the acute phase improves
prognosis. Furthermore, the safety of such intervention is not established.
METHODS: In an explanatory, randomized, controlled trial to test safety, 53 acute
(within 24 hours of ictus) stroke patients with mild to moderate hyperglycemia
(plasma glucose between 7.0 and 17.0 mmol/L) were randomized to receive either a
24-hour infusion of 0.9% (154 mmol/L) saline or a glucose potassium insulin (GKI)
infusion at 100 mL/h. The GKI consisted of 16 U human soluble insulin and 20 mmol
potassium chloride in 500 mL 10% glucose. Blood glucose was measured every 2
hours with Boehringer Mannheim Glycaemie test strips, pulse and blood pressure
were measured every 4 hours, and plasma glucose samples were taken every 8 hours.
Insulin concentration in the GKI was altered according to BM glucose values.
RESULTS: There were no statistically significant differences between the 2 groups
at baseline. Twenty-five patients received GKI, 1 of whom required intravenous
glucose for symptomatic hypoglycemia. Plasma glucose levels were nonsignificantly
lower in the GKI group throughout the infusion period. Four-week mortality in the
GKI group was 7 (28%), compared with 8 (32%) in the control group. CONCLUSIONS:
GKI infusions can be safely administered to acute stroke patients with mild to
moderate hyperglycemia producing a physiological but attenuated glucose response
to acute stroke, the effectiveness of which remains to be elucidated.
PMID- 10187882
TI - Cerebral blood volume in acute brain infarction: A combined study with dynamic
susceptibility contrast MRI and 99mTc-HMPAO-SPECT.
AB - BACKGROUND AND PURPOSE: The aim of this study was to correlate the abnormality in
cerebral blood volume (CBV) measured by dynamic susceptibility contrast-enhanced
MRI with that in cerebral blood flow (CBF) estimated by single-photon emission CT
with [99mTc]hexamethylpropylenamine-oxime in patients with acute ischemic stroke.
METHODS: Nine patients with unilateral occlusion of either the middle cerebral
artery or the internal carotid artery (4 men and 5 women; mean+/-SD age, 74.4+/
11.6 years) were studied within 6 hours after stroke onset. The relative CBV
(relCBV) and CBF (relCBF) in the lesions were defined relative to the
contralateral mirror regions. RESULTS: In the brain regions with mild (relCBF
>/=0.60), moderate (0.40=relCBF<0.60), and severe (relCBF <0.40) hypoperfusion,
the mean relCBV values were 1.29+/-0.31, 0.94+/-0.49, and 0.30+/-0.22,
respectively. The relCBV was significantly elevated in the brain areas with mild
hypoperfusion (P<0.001) and significantly reduced in the brain areas with severe
hypoperfusion (P<0.001). The relCBF was significantly better than the relCBV in
predicting the evolution of infarction (P<0.02). The probability of evolving
infarction for the hypervolemic (relCBV >1.0) regions was significantly lower
than that for hypovolemic (relCBV <1.0) regions in the relCBF range between 0.40
and 0.50 (P<0.02). CONCLUSIONS: In acute ischemic stroke within 6 hours of onset
the CBV can be either increased, normal, or decreased, depending on the severity
of hypoperfusion. The increased CBV has a protective effect on evolving
infarction. Although the CBF is a better predictor of tissue outcome, the CBV
measurement may help detect potentially salvageable brain tissue in the penumbra
with compromised blood flow.
PMID- 10187883
TI - Automatic embolus detection by a neural network.
AB - BACKGROUND AND PURPOSE: Embolus detection using transcranial Doppler ultrasound
is a useful method for the identification of active embolic sources in
cerebrovascular diseases. Automated embolus detection systems have been developed
to reduce the time of evaluation in long-term recordings and to provide more
"objective" criteria. The purpose of this study was to evaluate the critical
conditions of automated embolus detection by means of a trained neural network
(EMBotec V5.1 One, STAC GmbH, Germany). METHODS: In 11 normal volunteers and in
11 patients with arterial or cardiac embolic sources, we performed simultaneous
recordings from both middle or both posterior cerebral arteries. In the normal
subjects, we produced 1342 additional artifacts to use the latter as false
positives. Detection of microembolic signals (MES) was done offline from digital
audiotapes (1) by an experienced blinded investigator used as a reference and (2)
by a trained 3-layer-feed-forward neural network. RESULTS: From the 1342 provoked
artifacts the neural network labeled 216 events as microemboli, yielding an
artifact rejection of 85%. In microembolus-positive patients the neural network
detected 282 events as emboli, among these 122 signals originating from
artifacts; 58 "real" events were not detected. This result revealed a sensitivity
of 73.4% and a positive predictive value of 56.7. The spectral power of the
detected artifact signals was 16.5+/-5 dB above background signal. MES from
patients with artificial heart valves had a spectral power of 6.4+/-2.1 dB;
however, in patients with other sources of emboli, MES had an averaged energy
reflection of 2.7+/-0.9 dB. CONCLUSIONS: The neural network is a promising tool
for automated embolus detection, the formal algorithm for signal identification
is unknown. However, extreme signal qualities, eg, strong artifacts, lead to
misdiagnosis. Similar to other automated embolus detection systems, good signal
quality and verification of MES by an experienced investigator is still
mandatory.
PMID- 10187884
TI - Cerebral vasculopathy in HIV infection revealed by transcranial Doppler: A pilot
study.
AB - BACKGROUND AND PURPOSE: There is growing evidence for affection of cerebral
vessels during human immunodeficiency virus (HIV) infection. We prospectively
evaluated cerebrovascular reserve capacity (CRC) in HIV-seropositive patients by
transcranial Doppler sonography (TCD) after systemic administration of
acetazolamide. We hypothesized that a disturbed vasoreactivity would reflect the
cerebral arteries' involvement in HIV infection. METHODS: We assessed the mean
blood flow velocity (BFV) of the middle cerebral artery and its increase after
intravenous administration of 1 g acetazolamide (CRC) in 31 HIV-infected
individuals without symptoms of cerebrovascular disease (mean+/-SD age, 39+/-11
years). Stenotic or occlusive lesions of the large brain-supplying arteries were
excluded by color-coded duplex and transcranial imaging. BFV and CRC were also
measured in an age-matched group of 10 healthy control subjects. Patients were
classified according to clinical, laboratory, and neurophysiological parameters.
We also performed cerebral MRI (n=25) and rheumatological blood tests (n=26).
RESULTS: Baseline BFV and CRC both were significantly reduced in HIV-infected
patients as compared with control subjects (P<0.05, Student's t test). These
findings did not correlate with duration of seropositivity, helper cell count, or
other clinical, rheumatological, and neuroradiological findings. CONCLUSIONS: Our
findings support the hypothesis of a cerebral vasculopathy etiologically
associated with HIV infection.
PMID- 10187885
TI - Frontal bone windows for transcranial color-coded duplex sonography.
AB - BACKGROUND AND PURPOSE: The use of the conventional temporal bone window for
transcranial color-coded duplex sonography (TCCS) often results in difficulties
in obtaining angle-corrected flow velocity measurements of the A2 segment of the
anterior cerebral artery, the posterior communicating artery, and the midline
venous vasculature because of the unfavorable insonation angle. The same applies
to B-mode imaging of the frontal parenchyma. However, transorbital TCCS raises
problems with the insonation of the orbital lens. To overcome these drawbacks, we
studied the feasibility of frontal bone windows for TCCS examinations. METHODS:
In 75 healthy volunteers (mean age, 45.3+/-17.0 years; age range, 17 to 77
years), the circle of Willis and the venous midline vasculature were insonated
through a lateral and paramedian frontal bone window. Insonation quality of
parenchymal structures (B-mode) was graded on a 3-point scale depending on the
visibility of typical parenchymal landmarks. In a similar manner, the quality of
the color-/Doppler-mode imaging of the arteries of the circle of Willis and the
internal cerebral veins was assessed. In 15 patients (mean age, 62.7+/-13.7
years; age range, 33 to 83 years), the color-/Doppler-mode imaging quality of the
intracranial vessels before and after application of an ultrasound contrast
enhancing agent was compared. RESULTS: B-mode insonation quality was optimal to
fair in 73.3% of cases using the lateral and in 52.0% of cases using the
paramedian frontal bone window, with defined parenchymal structures used as
reference. Insonation quality decreased in those older than 60 years. In those
younger than 60 years, angle-corrected flow velocity measurements of the A2
segment of the anterior cerebral artery and the internal cerebral vein were
possible in 73.6% and 60.0%, respectively. Contrast enhancement resulted in a
highly significant improvement in the imaging quality of the intracranial
vessels. CONCLUSIONS: The transfrontal bone windows offer new possibilities for
TCCS examinations, although the insonation quality is inferior to the
conventional temporal bone window in terms of failure of an acoustic window. This
can be compensated for by application of an ultrasound contrast-enhancing agent.
PMID- 10187886
TI - Duplex scanning exploration of the ophthalmic artery for the detection of the
hemodynamically significant ICA stenosis.
AB - BACKGROUND AND PURPOSE: The North American and the European Carotid
Endarterectomy Trials demonstrated a significant benefit of surgery in preventing
stroke for patients with symptomatic hemodynamically significant internal carotid
artery (ICA) stenosis. Because the 3 angiographic methods of measuring carotid
stenosis provide discrepant results, the indication for surgery depends on the
method used for the evaluation of the angiogram. The goal of this study was to
verify whether color duplex scanning of the ophthalmic artery alone might be
reliable for detection of the extracranial hemodynamically significant ICA
stenosis. METHODS: Three groups of patients (351 total patients) with transient
ischemic attack or minor stroke referred for possible carotid endarterectomy were
examined by means of color duplex scanning of the ICA, transcranial Doppler,
color duplex scanning of the ophthalmic artery, and angiography of the ICA.
RESULTS: In the first group (n=31) the comparison of findings from each method
and the direct measurement of the residual lumen of plaque removed "en bloc"
showed that the findings of the ophthalmic artery color duplex scanning,
subdivided into 5 categories--NP (normal positive), LP (low positive), NF (no
flow), REV (reverse flow), PP (pathological positive)--were associated with the
best overall agreement (96.7%). The accuracy of the various categories of the
ophthalmic artery color duplex scanning signals was studied in the second group
of patients (n=200). The results pointed out that all but low positive categories
were associated with high diagnostic accuracy. Finally, the results obtained in
the third group (n=120) showed that a significant increase in the specificity of
the low positive signal could be obtained by processing this signal in terms of
pulsatility index and of transmission of pulsatility index. CONCLUSIONS: Our
results suggest that the diagnostic capacity of color duplex scanning for the
detection of ICA critical stenosis can be appropriately increased if it is
performed also at the level of the ophthalmic artery and if the Doppler signals
are processed on the basis of criteria we applied.
PMID- 10187887
TI - Mild carotid artery atherosclerosis: assessment by 3-dimensional time-of-flight
magnetic resonance angiography, with reference to intravascular ultrasound
imaging and contrast angiography.
AB - BACKGROUND AND PURPOSE: Our aim was to evaluate the usefulness of 3-dimensional
time-of-flight magnetic resonance angiography (3-D TOF MRA) in detection and
quantification of mild atherosclerotic changes of carotid arteries with reference
to intravascular ultrasound (IVUS) and contrast angiography. METHODS: TOF MRA at
1.5 T, IVUS, and selective digital subtraction angiography were performed on 31
extracranial carotid arteries of 27 patients (mean age, 52 years; age range, 17
to 75 years) undergoing neuroendovascular interventions. The atherosclerotic
lesions were registered, and quantitative measurements of plaque thickness,
luminal diameters, and diameter stenosis were independently performed for the
imaging modalities. RESULTS: Among 170 arterial segments analyzed, IVUS revealed
a total of 48 atherosclerotic lesions (mean diameter stenosis, 17%; range, 4% to
40%), only 25 of which were depicted on digital subtraction angiography. Analysis
of the axial source images of TOF MRA resulted in sensitivity of 77% to 83% and
specificity of 71% to 80% in lesion depiction for the 2 readers with reference to
IVUS. The values of diameter stenosis measured from MRA and IVUS were closely
interrelated (r=0.53 to 0.61, P<0.001). CONCLUSIONS: Three-dimensional TOF MRA is
feasible and moderately accurate for evaluation of mild atherosclerotic changes
of carotid arteries.
PMID- 10187888
TI - Aortic plaque in atrial fibrillation: prevalence, predictors, and thromboembolic
implications.
AB - BACKGROUND AND PURPOSE: Thoracic aortic plaque identified by transesophageal
echocardiography heightens the risk of stroke associated with atrial fibrillation
(AF). We sought to identify the prevalence, predictors, and implications of
aortic plaque in patients with nonvalvular AF. METHODS: Thoracic aortic plaque
was prospectively sought in 770 persons with AF with the use of transesophageal
echocardiography and classified as simple or complex on the basis of thickness
>/=4 mm, ulceration, or mobility. Clinical and echocardiographic features of
thromboembolism were correlated by multivariate analysis. RESULTS: Aortic plaque
was detected in 57% of the cohort, and complex plaque was detected in 25%. Both
were found more frequently in the descending than in the proximal aorta.
Potentially etiologic patient characteristics independently associated with
complex plaque included advanced age, history of hypertension, diabetes, and past
or present tobacco use. Comorbidities associated with aortic plaque were prior
thromboembolism, increased pulse pressure, ischemic heart disease, stenosis or
sclerosis of the aortic valve, mitral annular calcification (>10%), elevated
serum creatinine concentration, spontaneous echo contrast in the left atrium or
appendage, and left atrial appendage thrombus. The prevalence of complex plaque
in patients aged <70 years with <10% mitral annular calcification, without
ischemic heart disease, or without pulse pressure >/=65 mm Hg was 4% (95% CI, 1%
to 6%). CONCLUSIONS: Aortic plaque is prevalent in patients with AF and is
associated with atherosclerosis risk factors and with left atrial stasis or
thrombosis, which are themselves independent stroke risk factors. Since the
predominant location of complex plaque was in the descending aorta, the role of
aortic plaque as a source of embolism in AF is uncertain.
PMID- 10187889
TI - Carotid plaque, intima media thickness, cardiovascular risk factors, and
prevalent cardiovascular disease in men and women: the British Regional Heart
Study.
AB - BACKGROUND AND PURPOSE: B-mode ultrasound is a noninvasive method of examining
the walls of peripheral arteries and provides measures of the intima-media
thickness (IMT) at various sites (common carotid artery, bifurcation, internal
carotid artery) and of plaques that may indicate early presymptomatic disease.
The reported associations between cardiovascular risk factors, clinical disease,
IMT, and plaques are inconsistent. We sought to clarify these relationships in a
large, representative sample of men and women living in 2 British towns. METHODS:
The study was performed during 1996 in 2 towns (Dewsbury and Maidstone) of the
British Regional Heart Study that have an approximately 2-fold difference in
coronary heart disease risk. The male participants were drawn from the British
Regional Heart Study and were recruited in 1978-1980 and form part of a national
cohort study of 7735 men. A random sample of women of similar age to the men (55
to 77 years) was also selected from the age-sex register of the general practices
used in the original survey. A wide range of data on social, lifestyle, and
physiological factors, cardiovascular disease symptoms, and diagnoses was
collected. Measures of right and left common carotid IMT (IMTcca) and bifurcation
IMT (IMTbif) were made, and the arteries were examined for plaques 1.5 cm above
and below the flow divider. RESULTS: Totals of 425 men and 375 women were
surveyed (mean age, 66 years; range, 56 to 77 years). The mean (SD) IMTcca
observed were 0. 84 (0.21) and 0.75 (0.16) mm for men and women, respectively.
The mean (SD) IMTbif were 1.69 (0.61) and 1.50 (0.77) mm for men and women,
respectively. The correlation between IMTcca and IMTbif was similar in men
(r=0.36) and women (r=0.38). There were no differences in mean IMTcca or IMTbif
between the 2 towns. Carotid plaques were very common, affecting 57% (n=239) of
men and 58% (n=211) of women. Severe carotid plaques with flow disturbance were
rare, affecting 9 men (2%) and 6 women (1.6%). Plaques increased in prevalence
with age, affecting 49% men and 39% of women aged <60 years and 65% and 75% of
men and women, respectively, aged >70 years. Plaques were most common among men
in Dewsbury (79% affected) and least common among men in Maidstone (34%
affected). IMTcca showed a different pattern of association with cardiovascular
risk factors from IMTbif and was associated with age, SBP, and FEV1 but not with
social, lifestyle, or other physiological risk factors. IMTbif and carotid
plaques were associated with smoking, manual social class, and plasma fibrinogen.
IMTbif and carotid plaques were associated with symptoms and diagnoses of
cardiovascular diseases. IMTbif associations with cardiovascular risk factors and
prevalent cardiovascular disease appeared to be explained by the presence of
plaques in regression models and in analyses stratified by plaque status.
CONCLUSIONS: IMTcca, IMTbif, and plaque are correlated with each other but show
differing patterns of association with risk factors and prevalent disease. IMTcca
is strongly associated with risk factors for stroke and with prevalent stroke,
whereas IMTbif and plaque are more directly associated with ischemic heart
disease risk factors and prevalent ischemic heart disease. Our analyses suggest
that presence of plaque, rather than the thickness of IMTbif, appears to be the
major criterion of high risk of disease, but confirmation of these findings in
other populations and in prospective studies is required. The association of
fibrinogen with plaque appears to be similar to its association with incident
cardiovascular disease. Further work elucidating the composition of plaques using
ultrasound imaging would be helpful, and more data, analyzed to distinguish
plaque from IMTbif and IMTcca, are required to understand the significance of
thicker IMT in the absence of plaque.
PMID- 10187890
TI - Blockade of ATP-sensitive potassium channels in cerebral arterioles inhibits
vasoconstriction from hypocapnic alkalosis in cats.
AB - BACKGROUND AND PURPOSE: Recent studies have shown that the cerebral arteriolar
dilation from hypercapnic acidosis is blocked by agents which inhibit KATP
channels. These findings suggested that this response is due to opening of KATP
channels. Because the repose to CO2 is a continuum, with hypercapnic acidosis
causing vasodilation and hypocapnic alkalosis causing vasoconstriction, it would
be expected that the response to hypocapnic alkalosis would be due to closing of
KATP channels. There are no studies of the effect of inhibition of KATP channels
on the response to hypocapnic alkalosis. METHODS: We investigated the effect of 3
agents that in earlier studies were found to inhibit KATP channels--NG-nitro-L
arginine, hydroxylysine, and glyburide--on the cerebral arteriolar constriction
caused by graded hypocapnia induced by hyperventilation in anesthetized cats
equipped with cranial windows. RESULTS: Hypocapnic alkalosis caused dose
dependent vasoconstriction that was inhibited completely by each of the 3
inhibitors of KATP channels. The blockade induced by these agents was eliminated
in the presence of topical L-lysine (5 micromol/L). CONCLUSIONS: The findings
show that agents which inhibit ATP-sensitive potassium channels in cerebral
arterioles inhibit the vasoconstriction from hypocapnic alkalosis. These and
earlier results showing that inhibition of KATP channels inhibited dilation from
hypercapnic acidosis demonstrate that the response to CO2 in cerebral arterioles
is mediated by the opening and closing of KATP channels.
PMID- 10187891
TI - Thromboembolic events predispose the brain to widespread cerebral infarction
after delayed transient global ischemia in rats.
AB - BACKGROUND AND PURPOSE: Transient distal platelet accumulation after common
carotid artery thrombosis (CCAT) leads to hemodynamic, metabolic, and molecular
events that may influence the response of the postthrombotic brain to secondary
insults. We investigated how a thromboembolic insult would affect
histopathological outcome when combined with an ischemic insult induced 24 hours
later. METHODS: Three groups of rats underwent either (1) CCAT+10 minutes of
normothermic 2-vessel occlusion (n=6), (2) CCAT+sham ischemia procedures (n=6),
or (3) sham CCAT procedures+10 minutes of 2-vessel occlusion (n=6). At 7 days,
rats were perfused for quantitative histopathological and immunocytochemical
analysis. RESULTS: Rats undergoing combined insults (group 1) had significantly
larger areas of ischemic injury (P<0.05) within the cerebral cortex, striatum,
and thalamus compared with the other, single-injury groups. Increased ischemic
damage included selective neuronal necrosis, infarction, and focal hemorrhage. By
means of glial fibrillary acidic protein immunocytochemistry and lectin
histochemistry, reactive astrocytes and microglia were found to be associated
with widespread tissue necrosis. In contrast, infrequent infarction or CA1
hippocampal neuronal necrosis was observed in groups 2 and 3, respectively.
CONCLUSIONS: A prior thromboembolic event is a risk factor for widespread
cerebral infarction and hemorrhage when combined with a delayed ischemic insult.
The understanding of what factors enhance the susceptibility of the
postthrombotic brain to secondary insults may aid in the development of
neuroprotective strategies to be applied after transient ischemic attacks to
prevent the initiation of stroke.
PMID- 10187892
TI - "Tail sign" associated with microembolic signals.
AB - BACKGROUND AND PURPOSE: Transcranial Doppler ultrasound (TCD) can detect
circulating microembolic signals (MES). We focused our attention on tail signs
(TS), a signal associated with MES that appeared as a small reversal signal after
MES on the high time resolution spectral display. We examined MES and artifacts
in an animal study to determine whether TS were specific changes associated with
MES and investigated the characteristics of TS in both animal and clinical
studies. METHODS: In an animal study, adult pigs with venoarterial extracorporeal
membrane oxygenation and minimal anticoagulation therapy were used as a model for
cerebral embolism. After performing TCD monitoring with a multigated approach, we
did an offline analysis to investigate several parameters concerning MES and TS.
We also examined TS in patients in a clinical study. RESULTS: From a total of 362
MES investigated in the animal study, 72.9% were followed by TS. We could not
find any TS associated with artifacts. The time delay between TS and MES was
negatively correlated with the velocity of MES. MES almost always appeared first
in the proximal channel, whereas TS conversely appeared first in the distal
channel. In the clinical study, we were also able to observe TS associated with
MES. CONCLUSIONS: TS may represent emboli passing down a branch vessel or twisted
downstream vessel. TS are specific for MES and can be used as another criterion
for MES identification.
PMID- 10187893
TI - Amelioration of vasospasm after subarachnoid hemorrhage in transgenic mice
overexpressing CuZn-superoxide dismutase.
AB - BACKGROUND AND PURPOSE: To clarify the effect of superoxide dismutase (SOD) on
vasospasm after subarachnoid hemorrhage (SAH), we investigated sequential changes
in arterial diameter after SAH in transgenic mice overexpressing CuZn-SOD (SOD
1). METHODS: SOD-transgenic mice and nontransgenic littermates (35 to 40 g) were
subjected to SAH produced by endovascular perforation of left anterior cerebral
artery. At 4 hours and 1, 3, 7, and 14 days after SAH, the mice were perfused
with 10% formalin and consequently with a mixture of carbon black and 10% gelatin
to cast all vessels. Vasospasm was evaluated by measuring the diameter of the
left middle cerebral artery (MCA) with a microscope. RESULTS: In nontransgenic
mice, the diameter of the MCA on day 3 after SAH (110.5+/-20.5 microm [mean+/
SD]; n=16) was significantly reduced compared with that without SAH (138.5+/-14.5
microm; n=12) (P<0.01). Moreover, on day 3 after SAH, the diameter of the MCA in
SOD-transgenic mice (127. 9+/-20.2 microm; n=20) was significantly larger than
that in nontransgenic mice (110.5+/-20.5 microm; n=16) (P<0.05). CONCLUSIONS:
These results suggest that SOD is effective on the amelioration of vasospasm
after SAH and that oxygen free radicals, particularly superoxide, play an
important role in the pathogenesis of vasospasm after SAH.
PMID- 10187894
TI - Influence of platelet-activating factor on cerebral microcirculation in rats:
part 1. Systemic application.
AB - BACKGROUND AND PURPOSE: Platelet-activating factor (PAF) has been demonstrated to
have a mediator function in shock, with some of its deleterious effects being
attributed to its influence on microcirculation. Systemic PAF concentrations as
found in shock could also compromise the cerebral microcirculation. Our purpose
in the present study was to examine the influence of systemically applied PAF on
microvascular perfusion and leukocyte-endothelium interactions in cerebral
microvessels. METHODS: A closed cranial window technique was used for intravital
fluorescence microscopy of the brain surface. PAF was infused in concentrations
of 10(-12), 10(-9), and 10(-6) mol/L into the carotid artery (5 mL/h for 20 min)
of Sprague-Dawley rats (n=30). The selective PAF receptor antagonist WEB 2170BS
(2 mg/kg body weight) was used to inhibit specific PAF effects. RESULTS: The
number of leukocytes (cells/100 microm. min) rolling along or adhering at the
venular endothelium increased following infusion of PAF 10(-6) mol/L from 7.7+/
2.5 to 24.4+/-8.9 (P<0.05) and from 1.9+/-0.5 to 6.9+/-2.2 (P<0.05),
respectively, within 2 hours. Mean arterial pressure decreased from 92+/-22 mm Hg
to 49+/-17 mm Hg (P<0.05). The lower concentrations of PAF were less effective to
decrease mean arterial pressure but also induced leukocyte-endothelium
interactions. The intravenous administration of WEB 2170BS 15 min before the
infusion of PAF 10(-6) mol/L prevented both systemic hypotension and activation
of leukocyte-endothelium interactions. CONCLUSIONS: Increased systemic blood
levels of PAF as found during shock can not only cause systemic arterial
hypotension but also induce leukocyte-endothelium interactions in cerebral
venules. The activation of leukocytes was found to be independent of PAF-induced
arterial hypotension. The specificity of these results is confirmed by the
findings that WEB 2170BS could inhibit the PAF-induced systemic hypotension as
well as the activation of leukocytes.
PMID- 10187895
TI - Influence of platelet-activating factor on cerebral microcirculation in rats:
part 2. Local application.
AB - BACKGROUND AND PURPOSE: Platelet-activating factor (PAF) is involved in the
development of secondary brain damage after ischemic and traumatic brain injury.
On the basis of data from studies in peripheral organs, we hypothesized that PAF
mediated effects after cerebral injury could be secondary to alterations in
cerebral microcirculation. METHODS: Changes in cerebral microcirculation focusing
on leukocyte-endothelium interactions were quantified with the use of a closed
cranial window model in Sprague-Dawley rats (n=33) by means of intravital
fluorescence microscopy. The brain surface was superfused with PAF in
concentrations from 10(-3) (n=3) to 10(-12) mol/L (n=6) for 20 minutes (5 mL/h).
RESULTS: PAF 10(-4) mol/L (n=4) increased the number of rolling and adherent
leukocytes in venules from 9.7+/-0.4 to 19.7+/-2.3 cells/100 mm. min (P=NS versus
control) and from 2.2+/-0.5 to 4.3+/-0.7 cells/100 mm. min (P<0.05 versus
control), respectively. Lower concentrations did not elicit leukocyte-endothelium
interactions. Vessel diameters remained unchanged except for a transient increase
of arteriolar diameters during superfusion with PAF 10(-4) and 10(-6) mol/L
(n=6). Although only a limited area of the brain surface was exposed to PAF, the
mediator induced a significant dose-dependent transitory arterial hypotension and
caused irreversible circulatory shock at the high concentration (PAF 10(-3)
mol/L). Arterial hypotension after administration of PAF 10(-3) mol/L could be
attenuated by the intravenous pretreatment with the PAF antagonist WEB 2170BS.
CONCLUSIONS: PAF, when locally released after brain injury, can penetrate the
blood-brain barrier and induce systemic effects, including arterial hypotension.
Its role as a mediator in the development of secondary brain damage seems, at
least in the initial phase, not to be associated with disturbances of cerebral
microcirculation or activation of leukocytes.
PMID- 10187896
TI - Antiplatelet therapy in acute cerebral ischemia.
AB - BACKGROUND: Improved recognition of stroke signs and symptoms has paralleled the
development of pharmacological strategies that may be examined to reduce stroke
mortality and morbidity. Presently, tissue plasminogen activator is the only
therapy that significantly improves outcome in acute stroke, with no agent
demonstrating a significant reduction in mortality. SUMMARY OF REVIEW:
Antiplatelet agents are a heterogenous class of drugs that have been successfully
used for more than 2 decades in secondary stroke prevention. These agents include
aspirin, with or without dipyridamole, and more recently, the adenosine
antagonists ticlopidine and clopidogrel. However, studies of the use of
antiplatelet agents within 48 hours of the ictus have examined only aspirin. Only
1 study, the Multicentre Acute Stroke Trial-Italy (MAST-I), entered patients
within 6 hours of the ictus. These data suggest that an improvement in mortality
may be related to the speed of administration. No significant adverse events were
noted with early antiplatelet monotherapy. However, MAST-I did note a significant
increase in early mortality in patients receiving aspirin plus streptokinase, a
finding not adequately explained by an increase in the intracranial hemorrhage
rate. CONCLUSIONS: The use of antiplatelet therapy in acute stroke, clinical or
experimental, has only recently received attention. It is likely that the use of
antiplatelet agents for acute stroke therapy will be less restrictive than that
currently seen for thrombolytics. Future studies should include an examination of
those agents that have previously demonstrated efficacy in secondary stroke
prevention, most notably, aspirin. The recognition that all platelet stimuli
share a final common pathway that is dependent on the surface glycoprotein
IIb/IIIa (fibrinogen) receptor has resulted in the development of various agents
which block this receptor and are currently the focus for clinical trials. The
role of nitric oxide in stroke therapy will depend on minimizing the hypotensive
side effects of this agent. Stroke models are needed to provide preliminary data
on the efficacy of antiplatelet therapy, especially as relates to the interaction
of antiplatelet agents with thrombolytics.
PMID- 10187897
TI - Ischemic stroke in Poland and the United States.
PMID- 10187898
TI - No absolutes in neuromonitoring for carotid endarterectomy.
PMID- 10187899
TI - Advantages of transcranial power duplex imaging after contrast injection to
detect low flow in a moyamoya syndrome.
PMID- 10187900
TI - Abstracts of literature
PMID- 10187901
TI - Guidelines for the management of spontaneous intracerebral hemorrhage: A
statement for healthcare professionals from a special writing group of the Stroke
Council, American Heart Association.
PMID- 10187902
TI - Involvement of proteases in apoptosis.
AB - Genetically programmed (apoptotic) cell death plays a key role in cell and tissue
homeostasis and in pathogenesis of various diseases. However, the mechanisms
involved in apoptotic cell death are poorly understood. At present, the role of
proteases in key events of apoptosis is intensively studied and discussed and the
involvement of various proteolytic enzymes in the induction and development of
the cell death is well-recognized. Proteases of various classes participating in
apoptosis have been identified as well as some substrates of these proteases
whose cleavage is critical to cell viability; specific protease inhibitors which
prevent the cell death have been synthesized. This review summarizes new data on
proteolytic enzymes involved in apoptosis and considers the mechanisms of
activation of proteases upon induction of apoptosis and the pathways of their
involvement in the cell death. The participation of nuclear proteolytic enzymes
in the destabilization of chromatin structure and regulation of DNA fragmentation
by endonucleases in apoptotic cells is discussed.
PMID- 10187903
TI - Efflux of cyclic adenosine monophosphate from cells: mechanisms and physiological
implications.
AB - Although cyclic nucleotides are hydrophilic compounds, extracellular cAMP (cAMPo)
rapidly accumulates during the activation of adenylate cyclase. This review
considers the kinetic characteristics of cAMP transport through the plasma
membrane and its physiological implications. The influx and efflux of cAMP occur
via different carriers. At physiological concentrations of cAMPo, the influx of
cAMP does not significantly contribute to regulation of the intracellular content
of the cyclic nucleotide, but it is responsible for the accumulation of cAMPi in
experiments at [cAMP]o approximately 1 mM. In contrast, the high rate of cAMP
efflux is mainly responsible for normalization of [cAMP]i during long-term
activation of adenylate cyclase. The possible involvement of ATP-binding cassette
proteins (ABC proteins) in the efflux of cAMP from the cell is considered. In
procaryotes cAMPo is a signal molecule during the generation of cell colonies,
acting on special receptors that interact with GTP-binding proteins. Such
receptors have not been found in vertebrates, and in most cases the signal
functions of cAMPo are mediated by its degradation by extracellular enzymes with
subsequent activation of adenosine receptors.
PMID- 10187905
TI - Interaction of peroxynitrite and hydrogen peroxide with dinitrosyl iron complexes
containing thiol ligands in vitro.
AB - The interaction of peroxynitrite with thiolate dinitrosyl iron complexes (DNIC)
has been examined and compared with the interaction with H2O2. Peroxynitrite
oxidized DNIC containing various thiolate ligands--cysteine, glutathione, and
bovine serum albumin. Analysis of the oxidation suggested a two-electron reaction
and gave third-order rate constants of (9.3 +/- 0.5).109 M-2.sec-1 for DNIC with
BSA, (4.0 +/- 0.3).108 M-2.sec-1 for DNIC with cysteine, and (1. 8 +/- 0.3).107 M
2.sec-1 for DNIC with glutathione at 20 degrees C and pH 7.6. Peroxynitrite was
more reactive towards DNIC than towards sulfhydryls. Addition of sodium
dithionite after the reaction led to significant restoration of the EPR signal of
DNIC with cysteine. The reaction of glutathione DNIC with H2O2 was about 600
times slower than with ONOO- and not reversed by sodium dithionite. Thus
peroxynitrite, in contrast to hydrogen peroxide, changes the pool of
nitrosocompounds which can be responsible for interconversion, storage, and
transportation of nitric oxide in vivo.
PMID- 10187904
TI - Catalytic properties of mitochondrial NADH-ubiquinone reductase (Complex I).
AB - Qualitative and quantitative characteristics of the reactions catalyzed by the
most complex and least understood proton translocating unit of the mammalian
respiratory chain (NADH-ubiquinone oxidoreductase, Complex I) are described for
enzyme preparations differing in degree of resolution--from intact mitochondria
to homogeneous small enzyme fragments. Special attention is given to the problems
and pitfalls of reliable interpretation of the kinetic analysis of the enzyme
activities. Detailed analysis of the problems concerning the slow active/inactive
reversible enzyme transition is provided.
PMID- 10187906
TI - Kinetics of the interaction of rabbit skeletal muscle phosphorylase kinase with
glycogen.
AB - The kinetics of the interaction of rabbit skeletal muscle phosphorylase kinase
with glycogen was studied by the turbidimetric method at pH 6.8 and 8.2. Binding
of phosphorylase kinase by glycogen occurs only in the presence of Ca2+ and Mg2+.
The initial rate of complex formation is proportional to the enzyme and
polysaccharide concentration; this suggests the formation of a complex with 1:1
stoichiometry in the initial step of phosphorylase kinase binding by glycogen.
The kinetic data suggest that phosphorylase kinase substrate--glycogen
phosphorylase b--favors the binding of phosphorylase kinase with glycogen. This
conclusion is supported by direct experiments on the influence of phosphorylase b
on the interaction of phosphorylase kinase with glycogen using analytical
sedimentation analysis. The kinetic curves of the formation of the complex of
phosphorylase kinase with glycogen obtained in the presence of ATP are
characterized by a lag period. Preincubation of phosphorylase kinase with ATP in
the presence of Ca2+ and Mg2+ causes the complete disappearance of the lag
period. On changing the pH from 6.8 to 8.2, the rate of phosphorylase kinase
binding by glycogen is appreciably increased, and complex formation becomes
possible even in the absence of Mg2+. A model of phosphorylase kinase and
phosphorylase b adsorption on the surface of the glycogen particle explaining the
increase in the strength of phosphorylase kinase binding with glycogen in the
presence of phosphorylase b is proposed.
PMID- 10187907
TI - Stabilization of the enzyme--substrate complex of the mutant Asp-67Asn inorganic
pyrophosphatase from Escherichia coli by fluoride ions.
AB - Magnesium-supported PPi hydrolysis by the mutant Asp-67Asn E. coli
pyrophosphatase at saturating PPi and metal-activator concentrations in the
presence of NaF is followed by a gradual decrease in the initial rate of PPi
hydrolysis. The reaction occurs in two steps: first a complex containing enzyme,
pyrophosphate, magnesium, and fluoride ions is immediately formed, then its
conformation changes slowly. This enzyme--substrate complex stabilized by
fluoride is partially active and can be isolated by the removal of excess
fluoride by gel-filtration.
PMID- 10187908
TI - Steady-state kinetics of combined oxidation of hydroquinone and o-dianisidine by
hydrogen peroxide in the presence of horseradish peroxidase
AB - The steady-state kinetics of horseradish peroxidase-catalyzed oxidation of
hydroquinone was studied. Hydroquinone was shown to be a rapidly oxidizable
substrate of the peroxidase. Values of kcat and Km for this substrate were
determined in the pH range 4-7. The oxidation of hydroquinone and o-dianisidine
was distinguished when both were present in the reaction mixture. o-Dianisidine
was not oxidized until hydroquinone was completely converted. The rate of
hydroquinone oxidation by peroxidase in the presence of o-dianisidine was 3-10
times higher than the rate of its individual oxidation. The activator decreased
the Km for hydroquinone oxidation.
PMID- 10187909
TI - Mossbauer spectroscopic study of functional thermal destruction of iron--sulfur
proteins in membranes of thermophilic cyanobacteria synechococcus elongatus
AB - A mathematical model of the Mossbauer spectrum (80K) of native membranes of
Synechococcus elongatus was constructed on the basis of values of the quadruple
splitting (Delta) and the isomeric shift (delta) of the iron-containing
components of the photosynthetic apparatus obtained from the literature.
Thermally induced changes in the intensity of the spectral components of
membranes and isolated preparations of photosystem (PS) I were studied using this
model. It was shown that exposure of membranes to 70-80 degrees C causes a
decrease in the intensity of the components related to the FX, FA, and FB centers
and surface-located ferredoxins of PS I, an increase in the intensity of the
doublets of oxidized iron clusters that are nonspecifically absorbed by the
membranes, and formation of a new doublet. Spectral parameters of this doublet
(Delta = 3.10 mm/sec and delta = 1.40 mm/sec) are typical of inorganic hydrated
forms of reduced iron. Heating of PS I preparations also causes a decrease in the
intensity of doublets of the FX, FA, and FB centers and an increase in the
intensity of doublets of nonspecifically bound oxidized iron. However, this does
not cause formation of inorganic reduced iron. Comparison between the intensities
of the Mossbauer spectral components in intact and heated samples suggests that
the main source of reduced iron in membranes is surface-located ferredoxins.
Nonspecifically bound oxidized iron is formed at the expense of the FX, FA, and
FB centers. Disappearance of spectral components associated with ferredoxins and
accumulation of reduced iron in membranes occur within the temperature range
critical for inhibition of electron transport through PS I to oxygen. These
findings suggest that the thermally induced processes of accumulation of reduced
iron and inhibition of electron transport in PS I in membranes of thermophilic
cyanobacteria are interrelated and caused mainly by degradation of the Fe--S
centers of ferredoxins. The possible role of reduced iron accumulation in the
degradation of the photosynthetic apparatus induced by heat and other extreme
physical and chemical factors is discussed.
PMID- 10187910
TI - Site-specific endonuclease NspLKI is an isoschizomer of endonuclease HaeIII.
AB - Site-specific endonuclease NspLKI has been isolated and purified to functionally
pure state from soil bacterium Nocardia species LK by successive chromatography
on columns with phosphocellulose, HTP hydroxyapatite, and heparin-Sepharose. The
isolated enzyme recognizes the 5'-GG downward arrowCC-3' sequence on DNA and
cleaves it as indicated by the arrow, i.e., it is an isoschizomer of HaeIII. The
final enzyme yield is 1.105 units per gram of wet biomass. The enzyme is active
in the temperature range of 25-60 degrees C with an optimum at 48-55 degrees C;
it does not lose activity on storage for three days at room temperature. An
optimal buffer is HRB containing 10 mM Tris-HCl, pH 7.4, 200 microgram/ml
albumin, 10 mM MgCl2, and 100 mM NaCl.
PMID- 10187911
TI - Arachidonic acid regulation of prostanoid synthesis in macrophages.
AB - The dynamics of prostaglandin (PG) E2 synthesis by mouse peritoneal macrophages
during the delivery of the basic substrate, arachidonic acid (AA), from different
sources to the enzyme system of the cells was investigated. The dynamics of PGE2
synthesis in these cells was studied both after addition of exogenous AA and
after stimulating the liberation of AA from intracellular pools with the calcium
ionophore A23187. The kinetics of PGE2 synthesis when AA was supplied from
intracellular and extracellular sources were absolutely different. PGE2
metabolism and the inactivation of the key enzyme of PG synthesis (PGH-synthase)
during the reaction may be the regulating factors in the kinetics of PGE2
synthesis in the cells. For the different sources of AA in the cells, the rate
constants of PGE2 consumption (k2) and PGH-synthase inactivation in the course of
the reaction (kin) were calculated. The experimentally determined value of the
apparent rate constant kin was identical to the theoretically calculated kin
value for the case when AA was provided from an intracellular source. An observed
deceleration in the PGE2 synthesis kinetics from exogenous AA is characterized by
a 10-fold drop in the apparent kin and k2 values. The possibility of prostanoid
synthesis regulation at the level of the traditional, constitutive isoenzyme PGH
synthase-1 is discussed.
PMID- 10187912
TI - DNA-protein cross-links in different organs of mice induced by the combined
action of zinc and gamma-irradiation.
AB - Fractional whole-body gamma-irradiation of mice at total doses of 0. 5-1.5 Gy
induces increased DNA-protein cross-links (DPCs) in thymus, spleen, and brain,
whereas in liver no DPCs are detected. Chronic administration of zinc ions in
drinking water at concentration 10 mg/liter for 20-30 days increased DPCs in
thymus, spleen, brain, and liver of mice. The combined action of zinc ions and
gamma-radiation produced a significantly lower amount of DPCs than was induced by
the separate action of these agents.
PMID- 10187913
TI - DNA-protein cross-links in cells of internal organs of rats after fractional
irradiation at various doses.
AB - The influence of daily fractional irradiation of male Wistar rats for 30 days on
DNA-protein cross-links (DPC) in spleen, thymus, and liver cells was studied. The
level of DPC depended strongly on the daily dose of irradiation and the studied
organ. After irradiation at dose 0.5 Gy per day increased DPC level was detected
in all organs. The highest level was in the lymphoid organs and the lowest in the
liver. After irradiation at dose 0.3 Gy per day DPC formation was detected only
in the thymus. The data suggest the existence of a dose threshold for DPC
formation during fractional irradiation.
PMID- 10187914
TI - DNA-protein interactions between mammalian nuclear proteins and a GCC-element
included in a composite cis-acting element of mouse ribosomal protein L32
promoter.
AB - DNA-protein complex formation between the sequence GC(GCC)4 (GCC-element) of
mouse ribosomal protein L32 (rpL32) promoter and nuclear proteins of mouse and
human cells has been studied using gel retardation and South-Western blotting
methods. The rpL32 promoter fragment (-24.+11) was able to form specific
complexes with mouse and human nuclear proteins mainly due to the presence of the
GCC-element (-19.-6). DNA-protein complex patterns exhibited marked tissue
specificity. Three nuclear polypeptides of approximately 18, 28, and 50 kD that
bind to the rpL32 promoter region (-24.+11) have been detected in HeLa cells by
ligand blotting. At least one of them (18 kD) interacted with the GCC-element
directly. The same fragment of the promoter interacted only with one nuclear
polypeptide (28-31 kD) from human fibroblasts. DNA-protein complex formation
between the investigated rpL32 promoter fragment containing the GCC-element and
human fibroblast nuclear proteins is Zn2+-dependent. The method of functional
titration (in vivo competition in the CAT-test) revealed that the GCC-element
within the rpL32 promoter functions as a positive cis-acting transcriptional
element in NIH 3T3 cells. Thus, our data characterize the sequence GC(GCC)4 as a
functionally active cis-element included as a component in the more complex
(composite) cis-element of mouse rpL32 promoter exhibiting tissue-specific
properties. In various mammalian cell types the GCC-element can interact with
various nuclear proteins, and the mode of these interactions can be determined by
its relative position to other cis-elements in the regulatory sites of the
genome.
PMID- 10187915
TI - Effect of 2,2'-dipyridyl on accumulation of protoporphyrin IX and its derivatives
in yeast mitochondria and plasma membranes.
AB - The iron chelator 2,2'-dipyridyl (0.2 mM) more than fourfold increased the
concentration of protoporphyrin IX and also of its zinc-containing complex in
mitochondria of the yeast Saccharomyces cerevisiae. Protoporphyrin IX and a
chlorine derivative of protoporphyrin IX which fluoresces at 670-675 nm were
found in isolated plasma membranes of the yeast grown in the presence of 0.2 mM
2,2'-dipyridyl. The accumulation of endogenous porphyrins resulted in
intensification of lipid photoperoxidation in mitochondria and plasma membranes
and in a dramatically increased sensitivity of the cells to visible light (400
600 nm). The relative contribution of photodestruction of subcellular structures
to photoinduced cell inactivation is discussed.
PMID- 10187916
TI - Isolation, purification, and properties of aminopeptidase H from skeletal muscle
of the lizard Agama stellio stellio.
AB - Aminopeptidase H was isolated and purified from fresh skeletal muscle of the
lizard Agama stellio stellio by ammonium sulfate fractionation and successive
chromatographies on DEAE-cellulose, Ultrogel AcA-34, activated thiol-Sepharose
4B, phenyl-Sepharose CL-4B, and DEAE-cellulose again. This is the first report of
the isolation of aminopeptidase H from a reptile. The purified enzyme migrated as
a single band on SDS-PAGE. The molecular weight of the enzyme was 48 kD by SDS
PAGE and 384 kD on Ultrogel AcA-34 column chromatography. The optimum pH for
hydrolysis of L-leucine beta-naphthylamide (Leu-Nap) was 7.8. The Km values for
the hydrolysis of Leu-Nap and Nalpha-benzoyl-DL-arginine beta-naphthylamide
(BzArg-Nap) were 0.48 and 0.99 mM, respectively. These activities were strongly
inhibited by iodoacetic acid and leupeptin but were not affected by EDTA,
pepstatin, bestatin, or phenylmethylsulfonyl fluoride. The enzyme has been shown
not to hydrolyze proteins such as hemoglobin, BSA, myofibrillar proteins, and
sarcoplasmic proteins.
PMID- 10187917
TI - Effect of lignin on growth and tyrosinase activity of fungi from the genus
Aspergillus.
AB - The effect of lignin hydrolyzate (a waste product of the pulp and paper industry)
on the growth and tyrosinase activity of several strains of fungi of the genus
Aspergillus was studied. During fungal growth lignin was degraded with the
formation of soluble aromatic products. Accumulation of these products in the
growth medium leads to a 60-100-fold increase in tyrosinase synthesis. The
intensity of tyrosinase synthesis depends on the composition of the growth
medium. The ratio between lignin and glucose concentrations seems to be the main
factor; the activity was maximal at the ratio 2:1.
PMID- 10187918
TI - Non-classical protein Ser/Thr phosphatases: what are they for?
AB - Protein serine/threonine phosphatases are involved in regulation of diverse
cellular functions. This review is devoted to a novel group of protein Ser/Thr
phosphatases, rdgC/PP5, which has been recently discovered in animals, fungi, and
plants. Their structure, location, and possible functions are discussed.
PMID- 10187919
TI - Intracochlear acoustic pressure measurements: transfer functions of the middle
ear and cochlear mechanics.
AB - Direct intracochlear acoustic pressure recordings (from 20 to 20,000 Hz) are used
to measure the middle-ear transfer functions (forward and reverse) and to better
understand the cochlear mechanics in the guinea pig. In the forward direction,
the middle-ear transfer function is strongly dependent on the frequency and
presents a maximum of +30 dB at 1,000 Hz (bulla open). In the reverse direction,
the middle-ear transfer function looks like an ideal reverse middle-ear pressure
transformer with -35 dB gain and 0 degrees phase lag from 20 to 8,000 Hz (bulla
open, closed ear canal). Passive cochlear mechanics is studied with the help of
intracochlear pressure measurements and differential cochlear microphonic
potential recordings in the different turns.
PMID- 10187920
TI - Measurements of middle-ear function in the Mongolian gerbil, a specialized
mammalian ear.
AB - The middle ear of the Mongolian gerbil is thought to be specialized so that it
can hear the 3,000-Hz and lower sounds produced by approaching predators.
Evidence in the literature suggests several specializations: (1) an effect of the
large middle-ear air spaces in the gerbil is to increase the sensitivity of this
ear to sounds of 3, 000 Hz and lower in frequency; (2) the combined action of the
middle-ear cavity and the significant pars flaccida of the tympanic membrane in
the gerbil ear reduces the sensitivity to sounds of frequencies below 500 Hz.
This paper describes anatomical and functional measurements of stapes motion and
suggests that the stiffness of the gerbil ossicular system also acts to reduce
sensitivity to low-frequency sounds. The primary conclusion is that the frequency
dependence of the gerbil middle ear is the result of the interaction of multiple
factors, thereby complicating the relationship between single structural
specializations and overall function.
PMID- 10187921
TI - Mechanical properties of the middle ear system investigated by its pressure
volume relationship. Introduction to methods and selected preliminary clinical
cases.
AB - A new method is presented for the measurement of ear canal pressure changes in
response to tympanic membrane volume displacements, i.e. the pressure-volume
relationship (PVR) of the middle ear system. This method has several advantages
when compared to tympanometry; for example, it avoids phase delay and hysteresis
can be used as a variable thanks to bidirectional recordings. Moreover, dynamic
compliance is registered physically as changes in volume relative to pressure.
Normative data for 39 subjects are summarized along with preliminary data from
patients exhibiting various clinical conditions. The major findings are that
secretory otitis media with middle ear effusion results in significantly
increased hysteresis (leading to large errors when middle ear pressure is
determined by tympanometry), two types of ossicular discontinuity may be
distinguished by this method and that myringoplasty leads to a linear PVR in
contrast to the nonlinearity found in normal subjects.
PMID- 10187922
TI - Measurements of ossicular vibrations in the middle ear.
AB - The vibrations of the ossicles were measured with a laser Doppler vibrometer in
temporal bone specimens. The data contradicted the generally accepted view that
the malleus and incus rotate about a fixed axis. The vibrations of the ossicles
show a more complex pattern and, consequently, a more sophisticated model is
needed to portray the behaviour of the middle ear in a satisfactory manner. But
in turn models with many degrees of freedom make the identification process a
very difficult task. This dilemma can be resolved if the system is divided into
subsystems of less complexity where each subsystem can be studied in an
appropriate manner. The excitation by electrostatic forces, as applied in this
study, seems to be a powerful tool to make possible a study of parts of the
ossicular chain.
PMID- 10187923
TI - Observation of eardrum movements during quasi-static pressure changes by high
speed digital imaging.
AB - Under specific quasi-static pressure conditions during the Valsalva manoeuvre,
high-speed digital video pictures of eardrum displacements were recorded using an
endoscope and a Kodak Image Ektapro 1000 Motion Analyzer. A new type of data
interface enabled the complete videoclip to be saved and processed digitally,
and, with special mathematical algorithms, it is possible to generate three
dimensional computer animations of eardrum movements under quasi-static pressure.
The present study describes patterns of eardrum movements under static pressure
changes (Valsalva manoeuvre). These patterns were consistent with the results of
finite-element simulations of highly similar eardrum displacements reported by
other workers.
PMID- 10187924
TI - Modelling of components of the human middle ear and simulation of their dynamic
behaviour.
AB - In order to get a better insight into the function of the human middle ear it is
necessary to simulate its dynamic behaviour by means of the finite-element
method. Three-dimensional measurements of the surfaces of the tympanic membrane
and of the auditory ossicles malleus, incus and stapes are carried out and
geometrical models are created. On the basis of these data, finite-element models
are constructed and the dynamic behaviour of the combinations tympanic membrane
with malleus in its elastic suspensions and stapes with annular ligament is
simulated. Natural frequencies and mode shapes are computed by modal analysis.
These investigations showed that the ossicles can be treated as rigid bodies only
in a restricted frequency range from 0 to 3.5 kHz.
PMID- 10187925
TI - Identification of parameters for the middle ear model.
AB - This paper presents a method of parameter identification for a finite-element
model of the human middle ear. The parameter values are estimated using a
characterization of the difference in natural frequencies and mode shapes of the
tympanic membrane between the model and the specimens. Experimental results were
obtained from temporal bone specimens under sound excitation (300-3,000 Hz). The
first 3 modes of the tympanic membrane could be observed with a laser scanning
vibrometer and were used to estimate the stiffness parameters for the orthotropic
finite-element model of the eardrum. A further point of discussion is the
parameter sensitivity and its implication for the identification process.
PMID- 10187926
TI - Mechanical modeling and dynamical behavior of the human middle ear.
AB - Very serious injuries may result from impulse noise applied to the human ear. To
assess the hazard of a given impulse, its effects on the displacements and the
velocities of the structures in the middle and inner ear have to be evaluated.
Thus, it is necessary to consider the temporal pattern of applied pressure and
the resulting temporal response of the ossicular displacements and velocities.
These investigations have to be carried out in the time domain because the
relations in the frequency domain known from steady-state motion do not hold.
Mechanical models based on the finite-element approach and the multibody system
method are presented to describe the spatial motions of the eardrum and the
ossicles in the middle ear. The motion of all points of the ossicular chain can
be calculated using these models. The free vibrations as well as the general
solution of the excited system, consisting of a transient and a steady-state
part, are analyzed. Three different sound pressure sources are considered and the
dynamical response of the ossicular chain evaluated. It is not sufficient to
assess a particular impulse only by its peak pressure and a characteristic time
duration since the temporal response of the middle ear is strongly dependent on
the waveform of sound pressure. In particular, it is shown that in most of the
cases the first negative part of the pressure waveform is expected to cause the
worst damage.
PMID- 10187927
TI - Dynamics of middle ear prostheses - simulations and measurements.
AB - The efficient and systematic development of a middle ear prosthesis necessitates
the use of computer models for the prosthesis itself and the reconstructed middle
ear. The structure and parameters of the computer model have to be verified by
specific measurements of the implant and the reconstructed ear. To obtain a
realistic model of a reconstructed ear, three steps of modeling and measurements
have been carried out. To get a first approach of the coupling elements a
mechanical test rig representing a simplified reconstructed middle ear was built.
The velocity of the stapedial footplate was measured with a laser Doppler
vibrometer. The corresponding computer model was formulated, and the respective
parameters were determined using the measured dynamical transfer functions. In
the second step, a prosthesis was implanted into a human temporal bone without
inner ear. Exciting this system with noise, the velocity of the stapes footplate
was measured with the laser Doppler vibrometer. Based on the multibody system
approach, a mechanical computer model was generated to describe the spatial
motions of the reconstructed ossicular chain. Varying some significant
parameters, simulations have been carried out. To describe the dynamical behavior
of the system consisting of middle and inner ear, the computer model used in the
second step has been enlarged by adding a simplified structure of the inner ear.
The results were compared with in situ measurements taken from living humans.
PMID- 10187928
TI - Vibro-acoustic modelling of the outer and middle ear using the finite-element
method.
AB - In this study, a computer-based method called finite-element analysis is used to
predict the forced-frequency response of the ear, with and without an ossicular
replacement prosthesis (PORP 0362, Xomed Surgical Products). The method allows
visualisation of the dynamical behaviour of the tympanic membrane (TM) and of the
ossicles. The finite-element model is fully three-dimensional and includes both
ligaments and muscles, and accounts for damping caused by the TM, ligaments,
incudostapedial joint and the fluids of the inner ear. For validation, comparison
is made with experimental measurements of umbo displacement taken from the
literature. The translation and rotation (both anterior-posterior and inferior
superior) of the stapedial footplate are investigated. It is predicted that the
translatory motion of the footplate decreases with increasing frequency, except
when the frequency of the acoustic signal matches the natural frequencies of the
ossicular chain or outer ear canal. The tilting motion of the stapedial footplate
is also predicted to depend on frequency of excitation. The presence of a
prosthesis changes the dynamical response considerably by shifting the natural
frequencies of the ossicular chain. Ratios of stapes motion with and without the
prostheses are plotted as a function of frequency allowing this effect to be
clearly observed.
PMID- 10187929
TI - Determination of the shape and inertia properties of the human auditory ossicles.
AB - This paper describes a method to accurately determine the shape of the human
middle ear ossicles. If the density and the shape of a body are known, the
inertia properties can be calculated using commercially available software. The
inertia properties have been calculated for the stapes and for the incudomalleal
unit. Different rectangular views of the stapes and the incudomalleal unit are
shown to depict the position of the center of gravity and the position of the
principal axes of inertia.
PMID- 10187930
TI - Cochlear model with three-dimensional fluid, inner sulcus and feed-forward
mechanism.
AB - A three-dimensional model of the guinea pig cochlea using the phase-integral
method is presented. This model incorporates the viscous fluid effects in the
cochlea, dimensional and material property variation along the cochlear duct and
the active feed-forward mechanism of the outer hair cells. Two degrees of freedom
of the basilar membrane are considered, which results in two traveling waves
propagating along the duct for a given frequency. Basilar membrane response with
the active feed-forward mechanism compares favorably with published experimental
measurements.
PMID- 10187931
TI - Surgical outcomes in rhinosinusitis: what we know.
PMID- 10187932
TI - Effect of uvulopalatopharyngoplasty and genial and hyoid advancement on
swallowing in patients with obstructive sleep apnea syndrome.
AB - OBJECTIVE: Uvulopalatopharyngoplasty (UPPP) and genial and hyoid advancement
(GHA) are surgical techniques for the treatment of obstructive sleep apnea. These
techniques enlarge the oropharyngeal and hypopharyngeal airway, reducing collapse
at these levels. This study evaluated the effect of these procedures on
swallowing. METHODS: Fifteen patients who had undergone UPPP and GHA were
evaluated with a modified barium swallow to assess biomechanical changes in
swallowing. Specifically, velopharyngeal insufficiency; changes in tongue-base
movement, laryngeal elevation, and closure; epiglottic movement; and
pharyngoesophageal opening were examined. A brief swallowing questionnaire was
administered to assess for subjective changes in swallowing. RESULTS: Nine of 15
patients demonstrated abnormal objective swallow, of whom 5 reported normal
subjective swallowing. Six of 15 demonstrated normal objective swallowing. Of
these, 5 reported subjective change. CONCLUSION: UPPP with GHA may alter
biomechanical events during deglutition. However, little correlation exists
between subjective symptoms and objective findings. Further studies that include
preoperative and postoperative modified barium swallows are needed to identify a
cause-and-effect relationship.
PMID- 10187933
TI - Fine-needle aspiration biopsy: is anesthesia necessary?
AB - Fine-needle aspiration (FNA) of inflammatory and neoplastic head and neck masses
has become a widely used procedure in otolaryngology-head and neck surgery. Using
both subjective (patient perception) and objective (complication rate, accuracy)
criteria, this prospective study evaluated patients undergoing FNA with and
without anesthesia. Seventy-five patients were enrolled into 1 of 3 study groups:
group I, no anesthesia; group II, ethyl chloride spray; and group III, lidocaine
infiltrative anesthesia. In general, the ease of FNA, complication rates, and
accuracy rates were the same for the 3 groups. Patient perception and
satisfaction rates were improved in groups II and III. Use of topical or
infiltrative anesthesia may enhance the use of FNA in the anxious nervous patient
undergoing FNA of a neck mass.
PMID- 10187934
TI - Comparison of methods of airway evaluation in obstructive sleep apnea syndrome.
AB - OBJECTIVE: Head and neck examination, endoscopy, and cephalometric x-ray films
poorly predict surgical success in obstructive sleep apnea. It is hypothesized
that accurate measures demonstrate agreement and may statistically "cluster."
METHODS: Forty-two white men from a convenience sample of 60 patients had
physical examinations, upper airway endoscopies, and cephalometric x-ray films
reviewed. Clinically important groupings or those with linear correlation (>
0.05) were assessed with linear and logistic regression (P < 0.05). RESULTS:
Apnea hypopnea index was related to body mass index (b = 3.4, p < 0.0001),
posterior wall redundancy (b = 32.8, P = 0.0004), and endoscopic retropalatal
size (b = 29.5, P = 0.0046). Endoscopic retropalatal area was negatively
correlated to the cephalometric posterior airway space (b = 3.4, P < 0.0003).
Muller's maneuver and Malampatti scores were not associated with any measures.
CONCLUSIONS: Few features on airway evaluation associate or cluster in patients
with obstructive sleep apnea syndrome. Supine endoscopy may be promising because
it is associated with both the apnea hypopnea index and posterior airway space.
PMID- 10187935
TI - Current evaluation and treatment of patients with swallowing disorders.
AB - To determine the varied causes of oropharyngeal dysphagia and their respective
pathophysiology, a working understanding of the normal anatomy and function of
the highly integrated mechanism of swallowing is outlined. This information is
presented as the basis for a reasoned and detailed approach to the history,
physical examination, and endoscopic evaluation of normal and altered
oropharyngeal swallowing. The management of swallowing disorders depends on the
nature and magnitude of the responsible clinical condition. Conservative and
surgical approaches are discussed. These modalities and their indications are
described in detail.
PMID- 10187936
TI - Aspiration: cause and implications.
AB - The purpose of this investigation was to determine the overall prevalence of
aspiration in dysphagic individuals referred for a modified barium swallow and
the underlying anatomic and/or physiologic causes. A total of 166 patients were
seen during a 1-month period at 5 participating institutions. Aspiration was
detected in 51.2% of the patients. The most common causes were decreased
laryngeal elevation and delayed triggering of the pharyngeal motor response. A
history of aspiration pneumonia was significantly associated with the presence of
aspiration on modified barium swallow study. The presence of a protective cough
was present in only 53% of patients who aspirated, reinforcing the need for
appropriate radiologic assessment in patients with suspected dysphagia.
PMID- 10187937
TI - Timing of percutaneous endoscopic gastrostomy tube placement in head and neck
cancer patients.
AB - Percutaneous endoscopic gastrostomy (PEG) is an effective method for providing
alimentation in patients with upper aerodigestive tract carcinoma. Multiple
complications of this procedure have been reported, ranging from leakage around
the tube to tumor seeding of the abdominal cavity. This study was undertaken to
determine whether the timing of PEG tube placement with respect to primary tumor
extirpation led to a difference in the number and severity of observed
complications. The medical records of 43 patients with head and neck carcinoma
who had PEG tubes placed from 1995 to 1996 were retrospectively reviewed.
Comparisons of timing of PEG tube placement, complication, location, and stage of
the primary tumor were performed. In addition, the use of adjuvant therapy with
respect to the time of PEG tube placement and complications was evaluated. Of
these, 23% were done before and 30% during surgery at the time of primary tumor
resection (9 of 13 were after primary removal). One patient had an intraabdominal
abscess. Minor complications occurred in 15 of 43 patients (35%) and included
granulation tissue at the PEG site, leakage, and tube displacement. Eight of the
9 patients who underwent intraoperative PEG after tumor resection had no
complications. Patients who underwent PEG during or after surgery had
significantly fewer complications than those who underwent preoperative PEG or
had unresectable tumors (P = 0.038). The largest number of complications occurred
in patients who underwent preoperative PEG (57%) followed by patients whose
tumors were unresectable (31%). There was no statistical difference with regard
to tumor location or postoperative x-ray therapy in PEG complications. This study
demonstrates that PEG tube placement after tumor resection has the lowest
incidence of postoperative complications. Performing PEGs intraoperatively after
tumor resection can prevent the need for additional anesthesia to provide
alimentation in patients with upper aerodigestive tract carcinoma.
PMID- 10187938
TI - Long-term results of dermal grafting for the repair of nasal septal perforations.
AB - The closure of nasal septal perforations is a significant surgical challenge with
a high failure rate. Dermis placed between mucoperichondrial advancement flaps
may be an alternative. The usefulness of dermal grafting for the repair of nasal
septal perforations was initially investigated in an animal model. Four pigs had
1.5 x 2.5 cm perforations surgically created and closed with either temporalis
fascia or dermis placed under a local mucoperichondrial flap. The dermal graft
group had an average closure of 80% with histologically normal mucosal surfaces.
The temporalis fascia group had no closure. Fourteen patients with chronic nasal
septal perforations from iatrogenic causes, trauma, and drug abuse were repaired
with dermal grafting. Nine patients had complete closure, 3 patients had partial
closures, and 1 patient's graft dislodged on the first postoperative day. Dermal
grafts placed between mucoperichondrial flaps are a viable alternative for the
closure of nasal septal perforations.
PMID- 10187939
TI - Stapedectomy in children.
AB - Stapes surgery for correction of conductive hearing loss in adults with
otosclerosis is a well-established procedure. Its effectiveness in children,
however, has received less scrutiny in the literature. Previous studies from our
and other institutions demonstrated similar results in children and adults.
Between 1980 and 1994 stapedectomies were done on 95 ears of 81 patients younger
than 18 years (83 primary and 12 revisions). Data regarding age of onset, family
history, associated anomalies, surgical findings, technique, hearing results, and
complications were reviewed. Two groups were identified: congenital stapedial
fixation and juvenile otosclerosis. Patients with congenital stapedial fixation
had an earlier onset of hearing loss (3 vs 10 years, P < 0.001), a greater
incidence of abnormalities of the malleus and incus (25% vs 3%, P < 0.001), and a
slightly greater preoperative air-bone gap (35.2 +/- 12.9 vs 27.8 +/- 8.9, P =
0.002). Patients with otosclerosis had a greater frequency of a positive family
history of deafness (53% vs 10%, P < 0.001). Overall, 79% of primary cases and
89% of revision cases had an improvement in hearing, with mean postoperative air
bone gaps of 15 dB and 22 dB, respectively. The gap did not widen significantly
during the entire length of follow-up (mean 72 months). In primary cases, 59.1%
obtained a postoperative air-bone gap of 10 dB or less. Eighty-two percent of
children operated on for otosclerosis obtained excellent results (postoperative
air-bone gap < or = 10 dB), compared with only 44% of children with congenital
stapedial ankylosis (P = 0.02). In revision surgery, 29% of children obtained
excellent results. Poorer results in both cases of congenital stapedial fixation
and revision stapedectomy appear to be related to the greater incidence of
associated anomalies of the malleus and incus. Indications, technique,
complications, and considerations pertinent to childhood stapedectomy are
discussed.
PMID- 10187940
TI - Relationship of the posterior cricoarytenoid muscle to the posterior cricoid
lamina.
AB - OBJECTIVE: Early experiments in functional electrical stimulation of the
posterior cricoarytenoid muscle (PCA) in human beings have involved placement of
the electrode along the undersurface of the PCA. The anatomy of the posterior
cricoid lamina (PCL) was examined to obtain a quantitative understanding of this
region. METHODS: Thirty fresh-frozen cadaver larynges were dissected.
Measurements of the cricoid cartilage and PCA were obtained with a caliper or
calibrated probe. RESULTS: Twenty male and 10 female adult larynges were
examined. Sex differences were found for the height of the PCL. All larynges had
approximately 4 mm of exposed cartilage along the inferior surface of the PCL.
The origin of the PCA on the PCL was thinner in the medial-vertical attachment
than in the inferior-horizontal. The average inferolateral to superomedial
diagonal width of the PCA was 4 mm greater in the male than in the female
larynges. Asymmetry between the left and right sides was seen. CONCLUSIONS: The
PCA can be divided into 2 muscle groups based on its origin on the PCL as well as
its insertion into the muscular process of the arytenoid. The quantitative
information obtained has implications for electrode design and placement for
laryngeal stimulation.
PMID- 10187941
TI - Stage grouping reliability: TNM '97 versus TANIS in laryngeal cancer.
AB - PURPOSE: To compare the correlation of TANIS and TNM '97 with the survival rate
in laryngeal cancer. METHODS AND MATERIAL: From 1970 to 1990, 599 patients at the
ENT Clinic, University of Ferrara, had a complete follow-up and met the criteria
of enrollment. Data were analyzed by means of survival analyses (Kaplan-Meler and
Cox algorithms). RESULTS: Both systems showed a significant correlation with the
survival rate. TANIS advanced subcategories were better correlated with the
mortality rate than TNM stages IVa and IVb. Again, in the final statistical
model, TANIS was more highly correlated with survival rate than TNM.
PMID- 10187942
TI - Cystic fibrosis: an update for the otolaryngologist.
AB - Cystic fibrosis (CF) is an autosomal recessive disorder affecting exocrine gland
function. Formerly a deadly disease of infants and children, recent improvements
in antibiotics, nutritional therapy, and supportive care have extended the median
survival to adulthood. Patients with CF commonly go to an otolaryngologist with a
myriad of medical and surgical problems. Fortunately, the treatment and
management of CF have rapidly evolved during the past few years, and changes in
diagnosis, prevention, and treatment are occurring almost daily. As physicians on
the forefront of care for patients with CF, otolaryngologists need to be aware of
the new developments in the management of CF. An overview of CF is presented with
an emphasis on the current treatment strategy and what the next decade brings for
this formerly lethal disease.
PMID- 10187943
TI - Quality-of-life effects of psychosocial intervention in patients with head and
neck cancer.
AB - METHODS: Two studies of psychosocial interventions in head and neck cancer
patients at different stages of their disease were performed. We explored the
feasibility and effectiveness of different approaches, offered for the first time
to this population. The first study concerned long-term group psychological
therapy for patients with newly diagnosed head and neck cancer. Quality of life
was measured longitudinally for 1 year and compared with that of a control group.
The second study comprised a short-term psychoeducational program 1 year after
treatment for head and neck cancer. Quality-of-life assessments were made
repeatedly from diagnosis until 1 month after the intervention. RESULTS: Thirteen
patients started the psychological group therapy, and 8 of them completed both
the intervention and evaluation procedure. The quality of life of the therapy
group improved more than that of a control group in most areas measured during
the study year, in particular psychiatric morbidity, social functioning,
emotional functioning, and global quality of life. The results indicate benefits
from the therapy, although the therapy group scored worse than the control group
at diagnosis. Most of the variables representing functioning and symptoms
improved after the 1-week psychoeducational program, especially items reflecting
"trouble eating" and "problems enjoying your meals." Patients' judgments of the
intervention quality indicated satisfaction with all separate elements, mostly
education, about cancer and the opportunity to socialize with the other guests.
CONCLUSION: These pilot studies suggest that head and neck cancer patients can
benefit from different psychosocial interventions. Quality-of-life questionnaires
were well accepted and sensitive to changes during the studies. Thus our early
findings seem promising and would justify confirmation in larger studies.
PMID- 10187944
TI - Effects of systemic steroid treatment in chronic polypoid rhinosinusitis
evaluated with magnetic resonance imaging.
AB - BACKGROUND: The aim of this prospective study was to evaluate the efficacy of a
combined (local and systemic) steroid therapy on the extent of chronic polypoid
rhinosinusitis and patient symptoms. METHODS AND PATIENTS: Subjects of this study
were 20 patients with severe chronic polypoid rhinosinusitis with total or
subtotal narrowing of the all sinuses. A nasal budesonide spray (2 x 0.1 mg/day)
and an oral fluocortolone medication with a daily reduction during a 12-day
period (total dose: 560 mg = group 1) and a 20-day period (total dose: 715 mg =
group 2), respectively, were administered. Before and after the steroid treatment
we evaluated the extent of the sinusitis with MRI and patient symptoms with
symptom-related questionnaires. RESULTS: A significant reduction (> 30%) of the
chronic polypoid rhinosinusitis was observed in 50% of MRI findings. The steroid
effect on polypoid masses was heterogeneous in different anatomic areas
(maxillary sinus 40%, anterior ethmoid 19%, posterior ethmoid 33%, sphenoidal
sinus 61%, frontal sinus 46%). Most sinusitis-related symptoms were distinctly
diminished in most patients (80%). No major side effects were observed.
CONCLUSIONS: A combined short-term steroid therapy is highly effective in chronic
polypoid rhinosinusitis, reducing the mucosal inflammation mainly in the large
sinuses and reducing the incidence of symptoms significantly. However, this
therapy was insufficient in the anterior ethmoid and cannot replace the current
surgical treatment concept of the osteomeatal complex in CPR. The indication for
such a short-term steroid therapy is the preoperative treatment. It facilitates
functional endoscopic sinus surgery by reducing the extent of surgical
procedures, the time, and thereby the risks of sinus surgery.
PMID- 10187945
TI - Ventilation tubes and persisting tympanic membrane perforations.
AB - Surgical management of otitis media with effusion and recurrent acute otitis
media includes myringotomy and the use of ventilation tubes. Since this procedure
was reintroduced by Armstrong in 1954, it has become one of the most commonly
performed operations in otolaryngology. In most series perforation of the
tympanic membrane in some patients has been reported after spontaneous extrusion
or removal of the tympanostomy tubes. We present a retrospective review designed
to examine the incidence of persisting perforations of the tympanic membrane in
our series of 2604 operated ears. The study also identifies and analyzes the
variables and the contributing risk factors. Perforations occurred in 3.06% of
the ears: with a greater incidence in children younger than 5 years, when the
indication was recurrent purulent otitis media, with the use of long-term Goode T
tubes, in cases with repeated insertions of ventilation tubes, and in cases in
which postoperative otorrhea was frequent.
PMID- 10187946
TI - A unique complication of primary tracheoesophageal puncture: knotting of the
nasogastric tube.
PMID- 10187947
TI - Primary extramedullary plasmacytoma of the palate.
PMID- 10187948
TI - Hemangiopericytoma of the parapharyngeal space.
PMID- 10187949
TI - Type 2 first branchial cleft anomaly.
PMID- 10187950
TI - Vascular compression of the cochlear nerve identified by endoscopy during
acoustic neuroma surgery.
PMID- 10187951
TI - Case study of well-differentiated carcinoid tumor of the larynx and review of
laryngeal neuroendocrine tumors.
PMID- 10187952
TI - Spinal subdural hematoma after resection of an acoustic neuroma.
PMID- 10187953
TI - Subglottic stenosis: a complication of percutaneous tracheotomy.
PMID- 10187954
TI - Vascular lesion of the masseter presenting with phlebolith.
AB - When evaluating an intramuscular soft tissue mass, a large differential diagnosis
including both benign and malignant lesions must be considered. Because the
treatment of these masses can range from simple observation to radical surgical
excision, a minimally invasive but accurate method of diagnosis is desired. The
workup should include radiographic imaging. MRI is the modality of choice for
differentiating soft tissue lesions, although CT may be helpful in identifying
calcifications such as a phlebolith. Although usually unnecessary, a sialogram
can verify that a calcification lies within or outside the salivary ductal
system. In most cases a biopsy specimen is required to confirm the diagnosis.
However, if the imaging studies show characteristics consistent with a vascular
soft tissue mass, the finding of a phlebolith is pathognomonic for a benign
vascular lesion. If such a lesion is not causing significant cosmetic or
functional disability, it can be observed without the need for invasive biopsy or
treatment.
PMID- 10187955
TI - Laryngeal obstruction after inhalation of a penny from a metered-dose inhaler.
PMID- 10187956
TI - Watching aspiration after radiation therapy.
PMID- 10187957
TI - Head and neck manifestations of amyloidosis.
PMID- 10187958
TI - An unusual late reaction to facial injections.
PMID- 10187959
TI - Primary amyloidosis presenting as massive cervical lymphadenopathy with severe
dyspnea: a case report and review of the literature.
AB - Amyloidosis is an end point of several diseases in which the unifying
characteristic is the association and extracellular deposition of the insoluble
protein fibrils within various tissues and organs. We have discussed a variety of
clinical findings of primary amyloidosis with emphasis on its otolaryngologic
manifestations. This case represents the second report in the literature of a
neck mass resulting from a plasma cell dyscrasia and the first report of AL
disease producing such extensive cervical lymphadenopathy as to cause significant
respiratory compromise.
PMID- 10187960
TI - Nasopharyngectomy for recurrent high-grade mucoepidermoid carcinoma after
radiation failure.
PMID- 10187961
TI - Group A streptococcal toxic shock syndrome and associated respiratory distress.
PMID- 10187962
TI - Toxic shock syndrome after closed reduction of a nasal fracture.
PMID- 10187963
TI - Otolaryngologic features of Laurence-Moon-Bardet-Biedl syndrome.
AB - The most common otolaryngologic features associated with LMBBS include SNHL,
speech and language disorders, and oral and dental abnormalities. Early
otolaryngologic, audiologic, speech pathology, and dental evaluation of these
individuals is recommended. This is the first reported case of bifid epiglottis,
a rare congenital laryngeal anomaly, found in association with LMBBS. Most
patients with bifid epiglottis have additional congenital anomalies, most
commonly polysyndactyly. Polysyndactyly is a feature of both LMBBS and bifid
epiglottis and may be an early hallmark for the presence of other congenital
anomalies.
PMID- 10187964
TI - Devastating complications of acute pediatric bacterial sinusitis.
PMID- 10187965
TI - Incidence and management of tension pneumocephalus after anterior craniofacial
resection: case reports and review of the literature.
PMID- 10187966
TI - Management of epistaxis complicated by a previously undiagnosed aortic
coarctation.
PMID- 10187967
TI - Acute upper airway obstruction after recreational inhalation of a
hydrofluorocarbon propellant.
PMID- 10187968
TI - Nodular fasciitis arising in the external auditory canal.
PMID- 10187969
TI - Squamous cell metastasis from the tongue to the myocardium presenting as
pericardial effusion.
AB - Cardiac metastasis from head and neck cancer is rarely encountered. We present a
base-of-tongue squamous cell carcinoma with metastasis to the heart that was
diagnosed antemortem. Autopsy series indicate that tongue cancer may metastasize
more frequently to the heart than from other head and neck sites. However, none
of these studies was controlled. Most importantly, cardiac metastasis should be
suspected in any patient with cancer in whom new cardiac symptoms develop. The
diagnosis is best confirmed with two-dimensional echocardiography or cardiac MRI.
A myocardial or endocardial biopsy specimen can be obtained with angiographic
guidance. Despite the improvement in diagnostic capability, available treatments
are only palliative. All patients eventually die of their metastatic disease.
PMID- 10187970
TI - Granular cell tumor of the trachea.
PMID- 10187971
TI - Laryngopharyngeal reflux: a possible risk factor in laryngeal and hypopharyngeal
carcinoma.
PMID- 10187972
TI - Cancerous seeding of the tracheotomy site in patients with upper aerodigestive
tract squamous cell carcinoma.
PMID- 10187973
TI - Spindle epithelial tumor with thymus-like differentiation: a case report and
review of the literature.
PMID- 10187974
TI - Aneurysmal bone cyst of the temporal bone.
PMID- 10187975
TI - Aggressive cervical lymphoma presenting as airway obstruction.
PMID- 10187976
TI - Free flap reconstruction after near-total glossectomy in the child.
PMID- 10187977
TI - Early postoperative esophageal obstruction caused by enteral feeding concretions
in patients who have undergone laryngectomy.
AB - We report two cases of tube-feeding concretions causing esophageal obstruction in
patients after laryngectomy. The cause of tube-feeding concretions is unknown at
this time but probably involves esophageal stasis caused by esophageal
dysmotility, protein precipitation by acidic gastric contents, tube damage, and
concomitant use of sucralfate and other antacids. Although this is a rare
complication of nasogastric feedings, the diagnosis should be entertained in
cases in which postoperative esophageal obstruction is noted in head and neck
surgical patients.
PMID- 10187978
TI - Comparison of near-infrared spectroscopy and somatosensory evoked potentials for
the detection of cerebral ischemia during carotid endarterectomy.
PMID- 10187979
TI - Epizootic of equine influenza in 1969 in Poland.
AB - Epidemiological observations on the course and spread of equine influenza in
Poland during the 1969 epizootic were carried out. The dynamics of the spread of
the disease in the country are shown graphically by voivodship. The disease
incidence and mortality rates for the entire country are also shown. The highest
incidence of disease and mortality rates were found to be in November 1969.
A/equi-2/Warsaw/69 was identified as the causal virus. It caused the largest
epizootic in the country since 1954.
PMID- 10187981
TI - Thermal changes in cow's mammary gland after experimentally invoked inflammation
(mastitis).
AB - The purpose of the study was the evaluation of the thermal changes within mammary
gland in cows, after experimentally invoked inflammation, developed as a result
of 60 ml of 20% NaCl solution given directly into the udder (A and D quarters).
Three hours after injection, the increased' temperature of teats and their bases
by 2.26 degrees C and 0.58 degree C, respectively, was stated. The temperature
was still increased after 6 hours from NaCl solution injection. It was
accompanied by increase of heat flux from the skin surface by 50.17 mW/cm2 taken
from the teat surface, and by increased values of Burton Index--the tissue blood
supply index.
PMID- 10187980
TI - Studies on liver sufficiency of cows fed on food with unbalanced mineral
composition.
AB - In 90 cows of black white and red white race, aged 3-9 years and of 450 kg mean
body weight fed on food with low level of Ca, P, and Na, several parameters of
protein, carbohydrates and lipid liver metabolism before and after supply of
special mineral mixtures were evaluated. After the supply the increased
concentration of total protein, urea and cholesterol esters and decrease of
AspAT, AlAT, and AP activities were recorded in the blood. Cholesterol esters:
total cholesterol ratio improved and a slight increase of milk yield and content
of fat in milk was observed. Food mineral mixtures favourably influenced the
stabilization of liver metabolism.
PMID- 10187982
TI - Genetic and non-genetic determination of repeatability of blood and milk indices
in black-and-white cows.
AB - A herd of cows of the same age, kept in a stable system under controlled
environmental conditions, was used to estimate the repeatability of diagnostic
blood and milk indices in several stages of the I, II and III lactation.
Attention was paid to genetic and non-genetic sources of phenotypic variation.
Statistically significant values of the regression coefficient were found for the
following milk parameters: fat and protein content, milk density, calcium,
potassium and lysozyme levels, as well as the following blood parameters:
leucocytes' number, lymphocytes and neutrophils number, uric acid content,
leucocytes acid phosphatase activity, lysozyme and blood serum alkaline
phosphatase activity. Examined indices were analysed which proved to be suitable
for prognostic and breeding application.
PMID- 10187983
TI - Further studies on the etiopathology of malabsorption syndrome in broiler
chickens.
AB - The paper presents two cases of malabsorption syndrome in broiler chickens. The
results indicate that the etiological factor appears to be the virus agent which
causes necrosis in extra-excretional parts of the pancreas. During the course of
the disease disorders in the enzymatic activity of gammaglutamyltransferase,
leucylaminopeptidase and alanylaminopeptidase were observed. It consequently
leads to the deterioration of intestines digestion and resorption of feed
components. Application of Selcewet-Polfa to the diseased birds improved the
health of the birds, morphological picture of peripheral blood and mineralisation
of thigh bones. No radical improvement in the compensation of the final body
weight was recorded.
PMID- 10187985
TI - The effect of single administration of aflatoxin B1 and ACTH on the intensity of
acid phosphatase reaction in bursa Fabricii and in periellipsoidal lymphatic
tissue of the spleen of ducklings.
AB - The experiments were carried out with Peking breed female ducklings which on
their second day of life were administered into the crop a single dose of 1.5
micrograms of aflatoxin B1. On the 14th and 15th day from administration of
aflatoxin B1 the ducklings were intravenously injected a single dose of ACTH at 1
i.u. per 100 g bodyweight. Disturbances in the ducklings, initiated by aflatoxin
and then increased by ACTH, manifested themselves by a change in the intensity of
acid phosphatase reaction in the lymphatic organs tested. The occurrence of
differentiated APh reaction (but intensified differently as compared to that in
control ducklings) within bursa Fabricii and in periellipsoidal lymphatic tissue
of the spleen was the expression of unevenly changed reactivity of respective
tissues in those organs due to the action of aflatoxin B1. These results seem to
present an interesting starting point for further multidirectional experiments,
first of all in the range of immunological reactivity in birds.
PMID- 10187984
TI - Microscopic picture of the vesicular glands in young boars with respect to
feeding level.
AB - On 27 German Landrace boars studies were conducted to describe the effect of
feeding level during the growth period on the microscopic picture of vesicular
glands in boars at 5, 6 and 7 months of age. Investigations have shown that
differentiation of feeding level during the growth period affected the
development of internal structures of the parenchyma in the boars' vesicular
glands. The size of the tubules, their number within the field of vision and
height of glandular epithelium lining the tubules were the highest in the group
of animals fed at increased level.
PMID- 10187986
TI - Haematological parameters of the Polish Primitive Horses.
AB - Average values of chosen haematological parameters have been described in a
population of 90 clinically normal Polish Primitive Horses. The comparison of the
results with values given in literature for horses as a whole and for other
breeds enabled us to state that Polish Primitive Horses' blood is characterized
by relatively low values of RBC, PCV, segmented neutrophils and monocytes, and
high percentage of lymphocytes. It was demonstrated that values of some blood
parameters of examined animals are similar to typical results obtained for
primitive and cold-blooded horses. Moreover, it was proved that age, sex, and
season have influence upon many blood parameters' values of the Polish Primitive
Horses. More precise evaluation of results received with that breed will be
possible when that influence is taken into consideration.
PMID- 10187987
TI - The effect of folic acid addition on insulin level and some carbohydrate
metabolism indices in male rats fed with excess of methionine.
AB - Changes in insulin, plasma glucose and tissue glycogen were considerable and
statistically significant when the smaller dose of folic acid was given,
comparing with the bigger one. In both cases the physiological proportions
between examined parameters were not maintained.
PMID- 10187988
TI - Allometric growth of spleen and liver in black-white bovine fetuses (Bos
primigenius f. taurus).
AB - Growth relationships between spleen and liver weights and body weight and CR
length as well as between weights of liver and spleen in fetuses (145 males, 141
females) of black-white cattle. According to their body weights, the fetuses were
divided into 4 growth groups: I, to 1000 g; IIa, 1000-3490 g; IIb, 3500-7990 g;
III, over 8000 g. The relationships were described using appropriate allometric
growth equations (log Y = b log X + A) derived both for individual groups and for
the entire fetal period. Relative weights of the organs studied and the liver
spleen coefficient (L/S) were determined as well. The results are presented in
equations, tables, and graphs.
PMID- 10187989
TI - The ventricles of the brain in the N. American mink (Mustela vison (Brisson,
1756)).
AB - Using anatomical as well as radiographic and tomographic methods, sixty brains of
the N. American mink were examined. It was found that the brain consists of four
ventricles. Also, it was noted that the posterior horn was missing and that there
was the olfactory recess present in the lateral ventricle, a large-size
interthalamic connection present in the third ventricle, and a flat, necklace
like bottom in the fourth ventricle. Only recently, the ins and outs of the
mink's anatomical structure have begun to absorb anatomists. Apparently, it is
related to the fact that furry animals, among them the mink, are being
domesticated as if "before our eyes". For this reason and because of the easy
access to material, examining of the brain ventricles in the mink was taken up.
PMID- 10187990
TI - The effect of oestradiol-17 beta and progesterone on uptake1, uptake2 and on
release of noradrenaline in the uterine artery of ovariectomized pigs.
AB - Influence of oestradiol-17 beta and progesterone on neuronal uptake (U1) and
extraneuronal uptake (U2), and on the spontaneous neuronal and tissue release of
noradrenaline was investigated in isolated uterine artery obtained from an
ovariectomized pigs. It was found that oestradiol decreased U1 by 38.7% (p <
0.05), U2 by 78.2% (p < 0.01) and neuronal release by 55.4-63.0% (p < 0.05).
Progesterone decreased U2 by 80.5% (p < 0.01) and neuronal release by 71.7-76.4%
(p < 0.01). Simultaneous administration of oestradiol and progesterone led to the
inhibition of U2 by 93.9% (p < 0.01) and neuronal release by 69.6-73.8 (p < 0.01)
and to the rise of tissue release by 72.2-87.5% (p < 0.05-p < 0.01). Oestradiol
inhibited noradrenaline uptake and decreased it reserves in uterine artery of
pigs. This consequently decreased vasospastic adrenergic influence in the
oestrous phase of the cycle. Effect of progesterone on the noradrenaline uptake
was similar to that caused by oestradiol. Quantitative differences in the action
of these hormones on noradrenaline uptake were not significant and did not
explain their different influence on the vasotonus of the reproductive tract.
PMID- 10187991
TI - Uptake1, uptake2 and the release of [3H]-noradrenaline in uterine artery of pigs
during the oestrous cycle.
AB - Neuronal uptake (uptake1), extraneuronal uptake (uptake2) and the spontaneous
release of 2H-noradrenaline (NA) in uterine artery of swine on days 0, 1-2, 13-14
and 16-18 of the oestrous cycle were studied. It was found that uptake1 was
lowest on the day of ovulation (day 0) and then it increased by 37.4% (p < 0.05)
and by 93.7% (p < 0.01) on days 1-2 and 13-14, respectively. On days 16-18 of the
oestrous cycle uptake1 was insignificantly higher (9.3%) compared to the day 0.
Also uptake2 was the lowest on day 0 and next it increased to 180.1% (p < 0.01)
on days 1-2. Thereafter this value was still higher compared to day 0 but it had
decreasing tendency: 140.3% (p < 0.05) on days 13-14 and 113.8% on days 16-18 of
the oestrous cycle. Release of neuronal radioactivity was the lowest on day 0 and
then it increased by 40.0-44.2% (p < 0.05), 46.8-49.5% (p < 0.05) and 26.1-28.1%
(p > 0.05) on days 1-2, 13-14 and 16-18 of the oestrous cycle, respectively. The
release of extraneuronal radioactivity was the highest on day 0 (accepted as
100%) and similarly high (88.6-91.8%) on days 13-14 but markedly lower (28.3
36.0%; p < 0.05) on days 1-2 and 16-18 (43.9-50.1%; p < 0.05) compared to the
value on day 0 of the oestrous cycle.
PMID- 10187992
TI - Assay for endogenous heparin in plasma of livestock using a synthetic chromogenic
substrate.
AB - The levels of endogenous heparin in the plasmas of horses, cows, sheep and pigs
were determined with the use of synthetic chromogenic substrate benzoyl-isoleucyl
glutamyl-glycyl-arginyl-p-nitroanilide (S-2222). The lowest heparin
concentrations were stated in cattle plasma, the highest ones in the plasma of
pigs.
PMID- 10187993
TI - The estimation of factor VIII levels in horse, cattle, sheep and pig plasma by
the use of synthetic chromogenic substrate.
AB - Factor VIII level in horse, cattle, sheep and pig plasma was estimated by the use
of synthetic chromogenic substrate S-2222 (benzoyl-isoleucyl-glutamyl-glycyl
arginyl-p-nitronilide). The highest level of this factor was stated in pig, the
lowest one in sheep plasma.
PMID- 10187994
TI - The role of prefrontal cortex in the dopaminergic dysregulation of schizophrenia.
PMID- 10187995
TI - The relationship between dorsolateral prefrontal N-acetylaspartate measures and
striatal dopamine activity in schizophrenia.
AB - BACKGROUND: Pathology of dorsolateral prefrontal cortex and dysregulation of
dopaminergic neurons have been associated with the pathophysiology of
schizophrenia, but how these phenomena relate to each other in patients has not
been known. It has been hypothesized that prefrontal cortical pathology might
induce both diminished steady-state and exaggerated responses of dopaminergic
neurons to certain stimuli (e.g., stress). We examined the relationship between a
measure of prefrontal neuronal pathology and striatal dopamine activity in
patients with schizophrenia and in a nonhuman primate model of abnormal
prefrontal cortical development. METHODS: In the patients, we studied in vivo
markers of cortical neuronal pathology with NMR spectroscopic imaging and of
steady-state striatal dopamine activity with radioreceptor imaging. In the
monkeys, we used the same NMR technique and in vivo microdialysis. RESULTS:
Measures of N-acetyl-aspartate concentrations (NAA) in dorsolateral prefrontal
cortex strongly and selectively predicted D2 receptor availability in the
striatum (n = 14, rho = -.64, p < .01), suggesting that the greater the apparent
dorsolateral prefrontal cortex pathology, the less the steady-state dopamine
activity in these patients. A similar relationship between NAA measures in
dorsolateral prefrontal cortex and steady-state dopamine concentrations in the
striatum was found in the monkeys (n = 5, rho = .70, p < .05). We then tested in
the same monkeys the relationship of prefrontal NAA and striatal dopamine
overflow following amphetamine infusion into dorsolateral prefrontal cortex.
Under these conditions, the relationship was inverted, i.e., the greater the
apparent dorsolateral prefrontal cortex pathology, the greater the dopamine
release. CONCLUSIONS: These data demonstrate direct relationships between
putative neuronal pathology in dorsolateral prefrontal cortex and striatal
dopamine activity in human and nonhuman primates and implicate a mechanism for
dopamine dysregulation in schizophrenia.
PMID- 10187996
TI - A.E. Bennett Research Award. Reversal of phencyclidine-induced effects by glycine
and glycine transport inhibitors.
AB - BACKGROUND: Phencycline (PCP, "angel dust") and other noncompetitive antagonists
of N-methyl-D-aspartate (NMDA)-type glutamatergic neurotransmission induce
psychotic effects in humans that closely resemble positive, negative, and
cognitive symptoms of schizophrenia. Behavioral effects of PCP in rodents are
reversed by glycine (GLY) and other NMDA augmenting agents. In rodents,
behavioral effects of PCP are mediated, in part, by secondary dysregulation of
subcortical dopaminergic neurotransmission. This study evaluates effects of GLY
and GLY transport antagonists on behavioral and neurochemical consequences of PCP
administration in rodents. METHODS: Two separate experiments were performed. In
the first, effects of GLY on PCP-induced stimulation of dopaminergic
neurotransmission in nucleus accumbens were evaluated using in vivo microdialysis
in awake animals. In the second, effects of a series of GLY transport antagonists
were evaluated for potency in inhibiting PCP-induced hyperactivity. RESULTS: In
microdialysis studies, GLY significantly inhibited PCP-induced stimulation of
subcortical DA release in a dose-dependent fashion. In behavioral studies, the
potency of a series of GLY transport antagonists for inhibiting PCP-induced
hyperactivity in vivo correlated significantly with their potency in antagonizing
GLY transport in vitro. CONCLUSIONS: These findings suggest, first, that GLY
reverses not only the behavioral, but also the neurochemical, effects of PCP in
rodents. Second, the findings suggest that GLY transport antagonists may induce
similar effects to GLY, and may therefore represent an appropriate site for
targeted drug development.
PMID- 10187997
TI - Longitudinal assessment of methylphenidate effects on oral word production and
symptoms in first-episode schizophrenia at acute and stabilized phases.
AB - BACKGROUND: Some studies have reported psychotic symptom exacerbation during
"pharmacologic challenge" paradigms using dopamine agonists. Few studies,
however, have examined the effects of these agonists on neurocognitive functions
in patients with schizophrenia. This study assessed the effects of
methylphenidate infusion on an oral word production test with demonstrated
sensitivity to frontal lobe lesions, and on clinical state. METHODS: Patients
were tested at two different phases; at the onset of their first-episode of
schizophrenia (acute phase), and then again after they had responded to treatment
and were clinically stable (stabilization phase). During each phase, patients
were tested prior to and following methylphenidate infusion. Symptom clusters
(i.e., positive, negative, and disorganization) were formed from SANS and SADS-C
(+PD) ratings at each of these four timepoints. RESULTS: Patients produced
significantly more words at preinfusion and while stabilized, suggesting that
overall, decreased dopamine activity was associated with better word production.
Redundant errors (i.e., perseverations of previously mentioned words and
production of multiple words with the same roots) increased significantly
following infusion in the stabilized phase. Disorganization symptoms increased
significantly following infusion, regardless of study phase. CONCLUSIONS: These
findings are consistent with previous theoretical and empirical findings relating
dopamine activity to verbal output, a "redundancy bias" in cognitive control, and
exacerbation of disorganization symptoms.
PMID- 10187998
TI - A 1H-decoupled 31P chemical shift imaging study of medicated schizophrenic
patients and healthy controls.
AB - BACKGROUND: Current 31P spectroscopy research in schizophrenia has examined
phospholipid metabolism by measuring the sum of phosphomonoesters and the sum of
phosphodiester-containing molecules. Proton decoupling was implemented to measure
the individual phosphomonoester and phosphodiester components. This is the first
study employing this technique to examine schizophrenic patients. METHODS:
Multivoxel two-dimensional chemical shift in vivo phosphorous-31 magnetic
resonance spectroscopy with proton decoupling was used to examine a 50-cm3 volume
in prefrontal, motor, and parieto-occipital regions in the brain. Eleven chronic
medicated schizophrenic patients were compared to 11 healthy controls of
comparable gender, education, parental education, and handedness. RESULTS: A
significant increase in the mobile phospholipid peak area and its full width at
half maximum was observed in the medicated schizophrenic patients compared to the
healthy controls in the prefrontal region. Inorganic orthophosphate and
phosphocholine were lower in the schizophrenic group in the prefrontal region.
CONCLUSIONS: The increased sum of phosphodiester [mobile phospholipid + glycerol
3-phosphoethanolamine (GPEth) + glycerol-3-phosphocholine (GPCh)] in
schizophrenic patients, measured in earlier studies, arises from the phospholipid
peak (MP) and not the more mobile phosphodiesters (GPEth, GPCh) as was originally
suspected. A decrease in the phosphocholine component of the phosphomonoesters
was also observed in the schizophrenic patients. These findings are consistent
with an abnormality in membrane metabolism in the prefrontal region in
schizophrenics.
PMID- 10187999
TI - Smooth pursuit performance in families with multiple occurrence of schizophrenia
and nonpsychotic families.
AB - BACKGROUND: Eye tracking dysfunction (ETD) has been put forward as a trait marker
for biological susceptibility to schizophrenia with the hope of identifying a
link to specific cerebral lesions. METHODS: Eye movements were recorded using
infrared oculography in 8 families (67 members) showing multiple occurrence of
schizophrenia and in 9 nonpsychotic families (80 members). Triangle wave stimuli
at 15 degrees/s and 30 degrees/s were used and gains (eye velocity/target
velocity), rates and amplitudes of different saccade categories (catch-up, back
up, anticipatory saccades, and squarewave-jerks) were determined. RESULTS: In the
relatives, the same deficit in maintenance of smooth pursuit performance was
found as was seen in the schizophrenic patients. This deficit, which was not
observed in the nonpsychotic families, consisted of lower gains for leftward as
compared to rightward pursuit. This was emphasized most clearly at 30 degrees/s
and was associated with an excess of catch-up saccades in the schizophrenic
patients, whereas in the relatives a tendency to exhibit more and larger
anticipatory saccades was observed. CONCLUSIONS: The results confirm the
hypothesis that eye-tracking dysfunction is a phenotypic marker for genetic
liability to schizophrenia. Neurophysiologically, a cerebral dysfunction which
includes one or more of the oculomotor centers can be assumed in subjects who
carry a genetic susceptibility to schizophrenia.
PMID- 10188000
TI - Antiretroviral antibodies: implications for schizophrenia, schizophrenia spectrum
disorders, and bipolar disorder.
AB - BACKGROUND: Some retroviral antigens share structural homology within a group of
related retroviruses. It is possible that antibodies directed against one virus
may cross-react with antigens from a different virus in the group. METHODS: Using
this principle, the human immunodeficiency virus 1 (HIV-1) Western blot assay was
used as an available source of human retroviral antigens to screen serum samples
from an archived collection to ascertain whether there was an association between
serum antiretroviral antibodies and mental illnesses. RESULTS: A statistically
significant proportion (28/54, 52%) of patients suffering from psychiatric
disorders had serum antibodies that recognized at least one antigen present on
the blot, culminating in indeterminate HIV-1 tests. The majority of the reactive
samples were directed against the HIV-1 group antigens p24 and p17. These
findings contrast with those of nonpsychiatric patients, who had 4/16 (25%)
indeterminate blots. CONCLUSIONS: The results suggest exposure to retroviral
antigens related to those of HIV-1 in subpopulations of schizophrenic,
schizophrenic spectrum disorder, and bipolar disorder patients.
PMID- 10188001
TI - The current status of tardive dystonia.
AB - Tardive dystonia (TDt), a persistent dystonia associated with exposure to
neuroleptic drugs, is an uncommon disorder. It differs from tardive dyskinesia
(TDk) in epidemiology, clinical features, risk factors, pathophysiology, course,
prognosis, and treatment outcome. TDt seems to develop faster and is more
painful, distressing, and disabling than tardive dyskinesia. In this article,
evidence is reviewed on the face, descriptive, construct, and predictive validity
of this iatrogenic complication of antipsychotic drugs. It is suggested that TDt
should not be lumped together with TDk. It deserves a separate nosological status
as an independent diagnostic category. The subclassification of TDt into various
subtypes based on coexistence of other movement disorders is suggested.
PMID- 10188002
TI - Reductions in brain phosphatidylinositol kinase activities in Alzheimer's
disease.
AB - BACKGROUND: Converging lines of evidence suggest that alterations in the
intracellular trafficking of the amyloid precursor protein, its derivatives, and
other relevant proteins may contribute to the pathophysiology of Alzheimer's
disease (AD). Since phosphatidylinositol (PI) kinase plays a pivotal role in the
sorting and transport of newly synthesized proteins to their final destinations,
we explored the hypothesis that AD is associated with alterations in the specific
activities of these enzymes in postmortem brain tissue. METHODS: The specific
activities of soluble and particulate pools of PI 3-kinase and PI 4-kinase from
the frontal cortex were compared between 11 cases with histopathologically
confirmed AD and 11 nondemented controls matched for sex, race, age at death, and
postmortem interval. Potential associations of these activities with
sociodemographic and clinical features were also explored. RESULTS: AD was
associated with 43-59% reductions in the specific activities of the soluble forms
of both lipid kinases; but no significant change in the specific activities of
the particulate species. Associations of these specific activities with sex, age
at onset or death, duration of illness, postmortem interval, or densities of
morphologic lesions in the frontal cortex were not observed among the 11 AD
cases. CONCLUSIONS: In addition to regulating protein sorting and trafficking, PI
kinases participate in a wide range of cellular processes including protection
from apoptosis, differentiation and cell growth, regulation of the cytoskeleton,
and glucose metabolism. The results of this study suggest that one or more of
these alterations in AD may result from a common abnormality in PI kinase
regulation.
PMID- 10188003
TI - The calcium response of human T lymphocytes is decreased in aging but increased
in Alzheimer's dementia.
AB - BACKGROUND: A significant increase in the [Ca2+]i response of single T
lymphocytes to mitogenic stimulation with phytohemagglutinin is reported for 27
Alzheimer patients compared with 27 healthy gender- and age-matched control
subjects, regardless of gender. METHODS: The [Ca2+]i signals of T lymphocytes
were assessed using the Fura-2-AM method. RESULTS: In Alzheimer's disease (AD)
the reaction pattern is similar to that seen in a group of 27 young healthy
control subjects who exhibited a marked [Ca2+]i rise after stimulation. During
normal aging the reaction pattern of T cells is significantly attenuated in
comparison to that found in young subjects. In healthy control subjects
differences in age-related changes in calcium homeostasis are highly significant
among women, young women showing the most intense cell response. CONCLUSIONS: The
elevation of [Ca2+]i appears to be a prerequisite for apoptosis, which is
suggested to be involved in the neuronal death occurring in AD. An increased
[Ca2+]i in AD is consistent with processes leading to neurodegeneration in AD.
PMID- 10188004
TI - Effects of transcutaneous electrical nerve stimulation on memory and behavior in
Alzheimer's disease may be stage-dependent.
AB - BACKGROUND: In previous studies, transcutaneous electrical nerve stimulation
(TENS) was shown to result in improvements in nonverbal short-term and long-term
memory, verbal long-term memory, and verbal fluency in patients in an early stage
of Alzheimer's disease (AD). In addition, the patients' physical, social, and
affective functioning improved. As AD is a progressive disease, it was examined
in the present study whether TENS would still be effective in the midstage of AD.
METHODS: Sixteen subjects (70-91 years old) met the NINCDS-ADRDA criteria for
probable AD, as well as the criteria for stage 6 of the Global Deterioration
Scale (midstage AD). To evaluate treatment effects, the subjects underwent a
number of neuropsychological tests and two observation scales. RESULTS: Compared
to TENS in an early stage, TENS in the midstage of AD appears to yield less
beneficial effects, i.e., as for cognition only nonverbal short-term memory
improved. No treatment effects were observed for the patients' physical, social,
and affective functioning. CONCLUSIONS: In view of the small number of patients,
the clinical relevance of TENS in patients in a midstage of AD remains to be
confirmed in a larger group, after which more definite conclusions about the
stage-dependency of TENS in AD can be drawn.
PMID- 10188005
TI - Interindividual differences in active and passive behaviors in the forced
swimming test: implications for animal models of psychopathology.
AB - BACKGROUND: In common with other animal models of psychopathology, the forced
swimming test (FST) suffers from the fact that it involves normal animals.
Moreover, powerful antidepressant drugs such as the selective serotonin reuptake
inhibitors have been found to give false negatives in this behavioral test.
METHODS: To circumvent these theoretical and practical difficulties, we studied
the interindividual variability of the behavioral reactivity of rats in the FST.
The effects of fluoxetine treatment or of a stressful experience (repeated
testing in the FST) were analyzed on various behavioral responses. RESULTS: The
following observations were made in replicated experiments: 1) a dimensional
behavioral response from passivity to high reactivity in the FST; 2) an
antidepressant-like effect of fluoxetine only in a subgroup of animals
categorized as low responders on the dimension of passivity-reactivity; and 3) a
switch toward passive responses following a past experience of stress, which was
corrected by fluoxetine treatment. CONCLUSIONS: It is concluded that a
dimensional approach could improve the screening of antidepressant drugs and
could aid the development of new ones by identifying the biobehavioral
characteristics of responder and nonresponder subjects.
PMID- 10188006
TI - Chronic treatment with repetitive transcranial magnetic stimulation inhibits
seizure induction by electroconvulsive shock in rats.
AB - BACKGROUND: Studies in laboratory animals suggest that repetitive transcranial
magnetic stimulation (rTMS) and electroconvulsive shock (ECS) increase seizure
inhibition acutely. This study was designed to explore whether chronic rTMS would
also have seizure inhibition properties. METHODS: To this purpose we administered
rTMS (Magstim Rapid) and sham rTMS twice daily (2.5 T, 4-sec train duration, 20
Hz) to two groups of 10 rats for 16 days. The rTMS coil was a 50-mm figure-8 coil
held directly over the rat's head. Raters were blind to experimental groups. On
days 11, 17, and 21 (5 days after the last rTMS) ECS was administered with a
Siemens convulsator using three electrical charge levels. Variables examined were
the presence or absence of seizures and seizure length (measured from the
initiation of the tonic contraction until the end of the limb movement). RESULTS:
At day 11 rTMS had no effect on seizures, and both rTMS and sham rTMS animals
convulsed equally. At day 17, however, rTMS-treated animals convulsed
significantly less (both at presence/absence of seizures, and at seizure length)
than sham rTMS animals. At day 21 the effects of rTMS had disappeared.
CONCLUSIONS: These findings suggest that rTMS administered chronically leads to
changes in seizure threshold similar to those reported for ECS and ECT; however,
these effects were short-lived.
PMID- 10188007
TI - Psychometric evaluation of daytime sleepiness and nocturnal sleep onset scales in
a representative community sample.
AB - BACKGROUND: The public health importance of daytime sleepiness as a risk factor
for accidents, interpersonal problems, and decreased productivity has been
recognized. However, epidemiologic research on this topic has been limited by the
reliance on laboratory measures (i.e., the Multiple Sleep Latency Test-MSLT). Two
scales, daytime sleepiness and nocturnal sleep onset, have been identified from
the self-report Sleep-Wake Activity Inventory (SWAI) in a clinic sample and
validated against the MSLT. This study evaluates the replicability of the two
scales in a population sample and assesses potential thresholds in scale scores
that distinguish normal from pathologic levels of daytime sleepiness and
difficulty falling asleep. METHODS: The sample consisted of 2181 subjects 18-45
years old in the Detroit metropolitan area. All sleep characteristic information
covered the 2 weeks prior to interview. Split-half sample factor analyses were
conducted to assess replicability of the results. Distribution of scale scores
and their relation to construct validity variables were used to evaluate possible
thresholds. RESULTS: A two-factor model appeared to best account for the
variation among the 12 items from the SWAI. The two factors accounted for 50% of
the variance in both split-half sample analyses. The revised eight-item daytime
sleepiness and two-item nocturnal sleep onset scales showed good and fair
internal consistency respectively across both split-half samples. There appeared
to be a "natural break" in daytime sleepiness scale scores that was associated
with a substantial and consistent change in number of hours slept. No breaks
appeared in nocturnal sleep onset scores. CONCLUSIONS: This study replicated the
results of the clinic-based study and suggested a potentially useful diagnostic
threshold for self-report excessive daytime sleepiness. Epidemiology of sleep
depends on the ability to move from the laboratory to population surveys in
reliable and valid ways. Development of self-report is a step in that direction.
PMID- 10188008
TI - A quantified analysis of sleep electroencephalography in anorectic adolescents.
AB - BACKGROUND: Previous studies on sleep characteristics in anorexia nervosa have
led to controversial results. This may be due to either the heterogeneity of the
samples studied or to an intrinsic inadequacy of the scoring criteria. To obtain
a more detailed analysis we have investigated sleep characteristics in a group of
adolescents affected by anorexia nervosa using spectral analysis techniques.
METHODS: After a baseline night, the sleep-electroencephalograms of 10 adolescent
anorectic girls (age +/- SD = 14 +/- 2 years) and 10 age-matched control subjects
were recorded and processed by a fast Fourier transformation routine. RESULTS:
Anorectics showed an increased number of awakenings and wakefulness after sleep
onset and a reduction of sleep efficiency and slow-wave sleep. Spectral analysis
results revealed a significant reduction in the power spectral values of slow
wave activity (SWA; 0.5-4.5 Hz) band in all NREM-REM cycles of sleep and in the
undisturbed and stable stage 4. Moreover the anorectic group was characterized by
a concentration of SWA in the first NREM-REM cycle with an abrupt decay in the
second part of the night. A positive correlation (r2 = .58, p < .01) between body
mass index and the amount of SWA was found. CONCLUSIONS: Sleep of anorectic
patients seems to be characterized by a weakness of SWA producing mechanisms. The
positive correlation between body mass index and the amount of SWA appears to be
consistent with the neurobiological consequences of the malnutrition state.
PMID- 10188009
TI - Electroencephalographic responses to alcohol challenge in Native American Mission
Indians.
AB - BACKGROUND: Native Americans have some of the highest rates of alcohol abuse and
dependence, yet potential central nervous system risk factors responsible for the
problem drinking seen in some tribes remain relatively unknown. METHODS:
Background electroencephalographic (EEG) variants and response to alcohol were
investigated in 48 Native American Mission Indian men between 18 and 25 years
old. RESULTS: Subjects with 50% or greater Native American heritage had a
significantly higher proportion of low-voltage EEG variants. Within this sample
of Mission Indian men, however, a family history of alcohol dependence was
associated with a greater incidence of high voltage alpha EEGs. Mission Indian
men also evidenced a "less depressant, more stimulating" response to alcohol as
quantified by less alcohol-induced reductions in alpha, greater EEG stability,
and increased alcohol-induced beta activity. CONCLUSIONS: These findings
demonstrate that certain genetically regulated EEG variants that have been
previously associated with risk for alcoholism in Caucasians may also be more
common in these Mission Indian men. Additionally, EEG measures of response to
alcohol do not provide support for the commonly held idea that Indians are more
sensitive to the depressant effects of alcohol.
PMID- 10188010
TI - Serum iron in catatonic and noncatatonic psychotic patients.
AB - BACKGROUND: Since low serum iron has been reported in a variety of
neuropsychiatric motor disorders, this study was conducted to examine serum iron
in patients with a catatonic disorder. METHODS: Forty catatonic and 40
noncatatonic psychotic patients were studied in relation to serum iron levels.
The association of serum iron with other clinical variables was also examined.
RESULTS: Catatonics had significantly lower mean serum iron than noncatatonics.
Ferropenia (serum iron < 50 micrograms/dL) was significantly more prevalent in
the catatonic (35%) than in the noncatatonic (7.5%) group. Severity of catatonic
symptoms was inversely correlated with level of serum iron, this being due to the
negative catatonic symptoms (r = -.34, p = .002). CONCLUSIONS: A subgroup of
catatonic patients had ferropenia. Lower serum iron level was associated with
both the presence of a categorically defined catatonic syndrome and the severity
of the negative catatonic symptoms.
PMID- 10188011
TI - Extrapyramidal symptoms and neuropsychological deficits in schizophrenia.
AB - BACKGROUND: Extrapyramidal (EP) symptoms and neuropsychological (NP) deficits are
both frequently present among schizophrenia patients. EP symptoms, such as motor
slowing, could hinder performance on NP tests, yet little is known about the
relationship between EP symptoms and NP functioning among schizophrenia patients.
METHODS: Using a comprehensive NP test battery and standard ratings of EP
symptoms and other psychiatric characteristics, we conducted a cross-sectional
exploration of the association between EP symptoms and NP functioning among 96
middle-aged and elderly outpatients with schizophrenia. RESULTS: Severity of EP
symptoms was associated with worse NP performance, particularly the areas of
learning and motor skills. Regression analyses indicated that the relationship
between EP symptoms and NP deficits was not accounted for by slowed motor or
mental processing, demographic characteristics, severity of psychopathology,
dyskinesia, or medication status. CONCLUSIONS: The pathophysiological mechanisms
underlying EP symptoms and some NP deficits in schizophrenia may overlap.
PMID- 10188012
TI - Borrelia burgdorferi central nervous system infection presenting as an organic
schizophrenialike disorder.
AB - BACKGROUND: We report on a 42-year-old female patient who presented with a
schizophreniform disorder and complete relief of symptoms after specific therapy.
METHODS: Cerebrospinal fluid and magnetic resonance imaging findings led to the
diagnosis of Lyme disease. RESULTS: To our knowledge this is the first reported
case with an exclusive psychiatric manifestation of Lyme disease. CONCLUSIONS: In
case of first manifestation of psychotic disorder, although neurological symptoms
are lacking, Lyme disease should be considered and be excluded by cerebrospinal
fluid analysis.
PMID- 10188013
TI - Movement of flocks of laying hens in and out of the hen house in four free range
systems.
PMID- 10188014
TI - Behavioural and hormonal changes associated with sexual maturity in layer
pullets.
PMID- 10188015
TI - Effect of leg weakness on behaviour of broiler chickens following food
withdrawal.
PMID- 10188016
TI - Effect of environmental factors on ammonia and dust production and broiler
performance.
PMID- 10188017
TI - Poultry carcase compost for application in the UK.
PMID- 10188018
TI - Effect of photoperiod and daily food-access time on mortality and performance of
male broilers.
PMID- 10188020
TI - An economic analysis of a modified, enriched cage egg production system.
PMID- 10188019
TI - Atmospheric nitrogen losses from poultry excreta.
PMID- 10188021
TI - Feather pecking in adult laying hens: can it be associated with pecking at
inanimate objects?
PMID- 10188023
TI - Feather pecking damage in growing bantams is influenced by dietary tryptophan
concentration but not dietary protein source.
PMID- 10188022
TI - Welfare and productivity of restricted broiler breeder females fed ad libitum or
restricted after the peak of egg production.
PMID- 10188024
TI - Comparison of the reproductive system in turkeys with a high or low
susceptibility to uterine prolapse.
PMID- 10188025
TI - Comparative study of feathering in modern and traditional turkeys.
PMID- 10188026
TI - Expression patterns of candidate genes for tibial dyschondroplasia in chicken
growth plate chondrocytes separated on percoll density gradients.
PMID- 10188027
TI - Genetic mapping of the chicken prolactin receptor gene: a candidate gene for the
control of broodiness.
PMID- 10188028
TI - Effect of whole wheat and heat stress on a coccidial infection in broiler
chickens.
PMID- 10188029
TI - Incidence of skeletal muscle damage in selected and unselected strains of turkey.
PMID- 10188030
TI - Observations on pigmentation, hatchability and ultrastructure in guinea fowl
eggshells.
PMID- 10188031
TI - Determination of the true metabolisable energy of diets based on two wheat
cultivars of established variability in apparent metabolisable energy.
PMID- 10188032
TI - Effects of dietary wood charcoal on performance and fatness of broiler chicks.
PMID- 10188033
TI - Effect of tannin-binding agents, with or without enzyme supplementation, on the
dry matter digestibility and ME of faba beans.
PMID- 10188034
TI - Comparison of body weight responses to dietary lysine concentration in broilers
of two commercial lines and a 'relaxed-selection' line.
PMID- 10188035
TI - Real dry matter and nitrogen digestibility: further correction of true dry matter
and nitrogen digestibility of proteins in tube fed birds, using uric acid
corrected nitrogen values.
PMID- 10188036
TI - Effect of enzyme supplementation of UK-grown lupinus albus on growth performance
in broiler chickens.
PMID- 10188037
TI - Use of rations with up to forty per cent palm kernel meal for egg production.
PMID- 10188038
TI - Fat selection in broiler chickens treated with corticosterone.
PMID- 10188039
TI - Exogenous corticosterone and dietary colour preference in broiler chickens.
PMID- 10188041
TI - Effects of wheat source, heat treatment and enzyme inclusion on diet
metabolisability and broiler performance.
PMID- 10188040
TI - Apparent starch digestibility in near-isogenic wheats for broilers.
PMID- 10188042
TI - Dynamic modelling of Ca and P flows in layers: prospects to reduce dietary
digestible P-levels.
PMID- 10188043
TI - Vitamin E can alleviate the depressed egg production of heat-stressed laying
hens.
PMID- 10188044
TI - Apparent nutrient digestibility of cereal grain-based foods soaked in water for
broiler chickens.
PMID- 10188045
TI - Physiological responses of broiler chickens to the vibrations experienced during
road transportation.
PMID- 10188046
TI - Digitised fluoroscopy (DF) predicts breaking strength in osteoporotic avian bone
in vivo.
PMID- 10188047
TI - Relationship between metabolic rate and organ size in two strains of chicken.
PMID- 10188048
TI - Physiological responses of broilers to pre-slaughter lairage: effects of the
thermal micro-environment?
PMID- 10188049
TI - Correlations between yolk size and age, egg weight or body weight at sexual
maturity.
PMID- 10188050
TI - Lipid peroxidation and the antioxidant system of the brain of developing chicken
embryo.
PMID- 10188051
TI - Lipid peroxidation in avian semen: protective effect of seminal plasma.
PMID- 10188052
TI - Incidence of blood spots in yolks from phosphorus-deficient hens.
PMID- 10188053
TI - Determining broiler bone life history.
PMID- 10188054
TI - Molecular determinants of outcome in bladder cancer.
PMID- 10188055
TI - Cancer-testis antigens: targets for cancer immunotherapy.
PMID- 10188056
TI - Re-resection with brachytherapy for locally recurrent soft tissue sarcoma: is
there a leg to stand on?
PMID- 10188057
TI - NY-ESO-1 may be a potential target for lung cancer immunotherapy.
AB - PURPOSE: To evaluate the frequency of NY-ESO-1 expression in cultured lung cancer
cells and to determine if this cancer-testis antigen can be presented for
recognition by an HLA-restricted cytolytic T-cell clone specific for NY-ESO-1.
METHODS AND RESULTS: Reverse transcriptase and polymerase chain reaction
amplification techniques were utilized to screen a panel of lung and esophageal
cancer cell lines for expression of NY-ESO-1 encoding a recently identified
cancer-testis antigen. NY-ESO-1 expression was detected in 11 of 16 small cell
lung cancer lines, three of seven non-small cell lung cancer lines, and zero of
12 esophageal cancer lines. 5-Aza-2' -deoxycytidine induced expression of NY-ESO
1 in lung cancer cells. Expression of HLA-A31 by plasmid transfection or
retroviral transduction enabled recognition of lung cancer cells by an HLA-A31
restricted cytotoxic T lymphocyte clone specific for NY-ESO-1. CONCLUSIONS: NY
ESO-1 expression may be analogous to MAGE gene expression in lung cancer lines in
terms of frequency and mechanism of transcriptional regulation. Furthermore, NY
ESO-1 can be presented on lung cancer cells for recognition by HLA-restricted
cytotoxic T lymphocytes. Further investigation is warranted to determine if NY
ESO-1 can be exploited for the immunotherapy for lung cancer.
PMID- 10188058
TI - Re-resection with brachytherapy for locally recurrent soft tissue sarcoma arising
in a previously radiated field.
AB - PURPOSE: The use of further radiotherapy among patients with soft tissue sarcoma
that recurs in a previously irradiated area is controversial. Presented is a
review of our 7-year experience with brachytherapy for recurrent soft tissue
sarcoma. METHODS: A retrospective review was performed of 26 patients who
underwent perioperative brachytherapy between 1990 and 1997 for recurrent soft
tissue sarcoma. In all cases, the sarcoma recurred within a previously irradiated
field. After-loading brachytherapy catheters were placed at the time of surgical
extirpation of the sarcoma within a single-plane implant by use of 1-cm
intercatheter spacing. Insertion of the radioactive 192Ir wire was delayed until
the fifth to seventh postoperative day to allow initial wound healing. The
prescribed dose rate for the 192Ir wire ranged between 50 and 80 cGy an hour, and
the dose was specified at 0.5 cm from the plane of the implant. The anatomic
locations treated included lower extremity (N = 10), upper extremity (N = 7),
trunk (N = 7), and head and neck (N = 2). RESULTS: Total tumor extirpation,
confirmed by negative frozen section margins, was accomplished in all cases. The
mean dose of external-beam irradiation received before brachytherapy was 55.6 Gy
+/- 1.8 Gy (range, 30.0 to 70.3 Gy). The mean dose of radiation prescribed at the
implant procedure was 47.2 Gy +/- 1.6 Gy (range, 11.0 to 50.0 Gy). A tissue
transfer flap was placed over the bed of resection in 13 cases. Complications
occurred in five patients including, three with wound breakdown, one with
osteonecrosis, and with neuralgia. Operative intervention was required in four of
the five patients with complications; each of the patients requiring operative
intervention for wound-related complications had undergone primary wound closure
without tissue transfer. Recurrence of disease occurred in 13 patients: nine
local and four distant metastases. The median follow-up was 16 months (range, 2
to 73 months). The 5-year local recurrence-free, distant recurrence-free, disease
free, and overall survival rates after brachytherapy were 52%, 75%, 33%, and 52%,
respectively. CONCLUSION: Re-irradiation of recurrent soft tissue sarcoma by
brachytherapy in conjunction with resection can be performed with acceptable
complication rates. Local control can be achieved for the majority of patients
who would otherwise require more radical surgical procedures.
PMID- 10188059
TI - Increased thymidylate synthase gene expression in liver metastases from
colorectal carcinoma: implications for chemotherapeutic options and survival.
AB - OBJECTIVES: To determine the association of intratumoral thymidylate synthase
(TS) gene expression with resistance to fluoropyrimidines and to study the
association of TS gene expression with outcome in patients with liver metastases
from colorectal cancer. METHODS: Intratumoral TS gene expression was measured by
reverse transcriptase and polymerase chain reaction in 33 patients with liver
metastases from colorectal carcinoma. Fifteen patients underwent resection, and
18 were treated with chemotherapy only. Patients with high levels of TS gene
expression were compared to those with low levels of TS gene expression. RESULTS:
All patients with a high level of TS gene expression were nonresponders to
fluoropyrimidine chemotherapy. Median survival in patients with unresectable
disease was shorter in those who had high levels of TS gene expression (7 months
vs 15 months, P = 0.02). After hepatic resection, median disease-free interval
was shorter in patients with high levels of TS gene expression (5 months vs 18
months; P = 0.004). Similarly, survival was shorter after resection in those with
high TS gene expression (17 months vs 43 months, P = 0.0002). DISCUSSION:
Increased TS gene expression is associated with a poor outcome in patients with
liver metastases from colorectal carcinoma, whether resected or treated by
chemotherapy only. This is related in part to reduced responsiveness to
chemotherapeutic agents, but it also reflects inherently more aggressive behavior
of metastases.
PMID- 10188060
TI - A phase II evaluation of all-trans-retinoic acid plus interferon alfa-2a in stage
IV melanoma: a Southwest Oncology Group study.
AB - BACKGROUND: Interferon alfa has modest but definite activity in the treatment of
metastatic melanoma and is the only agent currently available for adjuvant
therapy of high-risk resected disease. A variety of retinoic acid derivatives
have been shown to be synergistic with interferon alfa in vitro and in vivo, with
nonoverlapping toxicities. If promising combinations of interferon alfa and
retinoids could be developed for melanoma patients, they would have clinical
relevance for the treatment of advanced as well as localized disease. PURPOSE: To
determine the efficacy and toxicity of a combination of interferon alfa-2a and
all-trans-retinoic acid in patients with measurable metastatic melanoma, the
South-west Oncology Group conducted a phase II clinical trial. PATIENTS AND
METHODS: Fifty-seven patients with measurable metastatic melanoma (American Joint
Committee on Cancer stage IV) were entered; five patients were unevaluable.
Treatment consisted of oral all-trans-retinoic acid (37.5 to 75 mg/m2 orally
twice daily for 21 days followed by 7 days' rest) plus subcutaneously
administered interferon alfa-2a (6 MU/m2 three times a week). RESULTS: Two
complete and three partial responses were observed among 52 evaluable patients,
for an objective response rate of 10% (95% confidence interval 3% to 21%).
Responses were seen only in patients with pulmonary, nodal, or subcutaneous
metastases, and lasted from 4 to 23+ months. Median survival for the 52 patients
was 8 months. Side effects were tolerable but significant, with one case of grade
IV anemia and 92% of patients experiencing at least grade II toxicity. Flu-like
symptoms were the most commonly reported side effects. There was one case of
grade III hyperlipidemia. CONCLUSION: The combination of recombinant human
interferon alfa-2a with all-trans-retinoic acid did not result in a greater
percentage of objective responses or a longer overall survival than that
associated with interferon alfa alone. This combination cannot be recommended for
further evaluation in melanoma in either the advanced disease or the adjuvant
settings.
PMID- 10188061
TI - Malignant hypoglycemia associated with a large mesenchymal tumor: case report and
review of the literature.
AB - PURPOSE: To examine hypoglycemia associated with a non-islet-cell tumor caused by
the secretion of abnormal insulinlike growth factors. PATIENT AND METHODS: We
describe a 54-year-old woman with a massive solitary fibrous tumor who
experienced worsening hypoglycemia with suppressed levels of insulin and
insulinlike growth factor I but abnormally "normal" levels of insulinlike growth
factor II. RESULTS: Efforts to control her symptoms with frequent meals,
prednisone, and intravenous dextrose infusions were only partially successful.
Attempts at reducing the tumor size by embolizing its arterial supply and
percutaneous alcohol injections were unsuccessful, and the patient died 24 hours
after surgical debulking. DISCUSSION: Patients with non-islet-cell tumor
hypoglycemia usually have abnormally high levels of an incompletely processed
precursor of insulinlike growth factor II, which is more bioavailable than the
normal molecule. In some patients, treatment with corticosteroids and growth
hormone increases blood sugar levels, but the most effective therapeutic approach
is to resect or debulk the tumor.
PMID- 10188062
TI - Successful treatment of a patient on adrenal steroid replacement therapy with
high-dose bolus interleukin-2 for metastatic renal cell carcinoma.
PMID- 10188063
TI - Evaluating services for children with disabilities and their families.
PMID- 10188064
TI - Models of service support for parents of disabled children. What do we know? What
do we need to know?
AB - Research carried out over a number of years provides a consistent picture of the
experiences and needs of parents of disabled children. Recent studies, based on
models of stress and coping, have identified factors which relate to high or low
levels of parental distress. Whilst this research can provide useful information
for service development, there appears to have been little change over the years
in parents' reports of unmet need. It is clear that parental need covers a wide
range of aspects of family life and holistic models of service support are
required. Although evaluation studies which identify models of services that can
change this situation are few, there are positive examples of models of support.
The paper reviews the findings of such evaluation and identifies a number of
important characteristics of effective service models.
PMID- 10188065
TI - Conceptual frameworks in evaluation of multidisciplinary services for children
with disabilities.
AB - Child disability services are under pressure to evaluate what they provide.
Evaluation encompasses both the procedures they adopt and the outcomes for their
clients, that is, for children and families. This paper presents practical
frameworks for service evaluation, with examples from experience and from
published literature. Individual services cannot carry out evaluation of the
clinical effectiveness of particular interventions, but they can clarify their
goals, institute regular audit projects, develop guidelines for their practice
through participatory evaluation, and sample parents' views of the quality of the
services they provide. Practical suggestions are made for the measurement of
outcomes for individual children and families.
PMID- 10188066
TI - Service evaluation and development: experience of a paediatric disability team.
AB - Classical audit frameworks encourage the use of audit cycles, with performance
being evaluated against predefined quality targets and modified accordingly. This
approach has obvious validity in clinical settings where treatments have very
clear endpoints and outcome measures can be prioritized with ease. The situation
becomes more complex in disability service settings, where the impact of clinical
intervention is often qualitative rather than quantitative, and where management
strategies are dependent on working in partnership with families, purchasers and
other professional colleagues. There is thus a danger of neglecting aspects of
service delivery which are of major importance to one sector of this extensive
network. To ensure that service goals and standards comprehensively reflect the
specific concerns of all parties, it is proposed that measures of service quality
should be defined within the context of a dynamic multi-user framework.
Development of such a framework is dependent on collating information on specific
needs from parents, referrers, purchasers and other involved professionals, and
determining areas of overlap, as well as areas of potential conflict. Audit
techniques for key issues can then be devised, alongside a timetable to revisit
these issues at appropriate intervals. Application of this approach is
illustrated by reference to our own paediatric disability service.
PMID- 10188067
TI - Evaluating child disability programmes: the role of commissioners.
AB - The paper briefly reviews the role of a health care commissioner in planning and
evaluating children's disability services, an area with a strong statutory
framework but a paucity of guidance. It also explores how different aspects of
evaluation apply to commissioning.
PMID- 10188068
TI - Issues to consider in the evaluation of speech and language therapy for preschool
children.
AB - This paper reviews some of the methodological issues involved in the design of a
randomized controlled trial currently underway in Bristol. The trial compares the
progress of preschool children randomly allocated to a 'watching-waiting' control
group with the experimental group who have immediate access to therapy. This
paper reviews a number of relevant studies, which have either followed up
preschool children with early language delays or have investigated the effects of
therapy with this age group. The basic design of the trial is outlined along with
a discussion of the sample, the measurements used and the therapy given.
PMID- 10188069
TI - How do Child Development Teams work? Findings from a UK national survey.
AB - The area of child disability is the 'Cinderella' of community child health
services. It lacks a clear commissioning model, agreed quality standards or
guidance on the level of resources required. In this climate of uncertainty, a
national survey of Child Development Teams was undertaken in order to describe
their basic structure and processes. The paper reports information from 242
multidisciplinary teams providing local services, with statutory funding, to
children with neurodevelopmental disability and their families. The picture
presented is encouraging in part. For example, 79% of teams operate from a Child
Development Centre, which may be expected to enhance team communication. In terms
of the initial assessment process for a developmentally delayed child, most teams
(91%) report that they would hold a case discussion afterwards, although only 74%
would always include parents, and only 70% always give their report(s) to
parents. The impression of management practices is weak, with only 62% giving a
clear answer about who manages the team, and less than half having a written
policy or contract for the team's work. The survey findings provide a sampling
framework from which further evaluative research can be generated.
PMID- 10188071
TI - Bone marrow transplantation for autoimmune diseases.
AB - Autoimmune diseases afflict approximately 2% of the US population and span
virtually every medical specialty. Most patients with autoimmune diseases have a
normal life expectancy and are managed conservatively; however, a subset of
patients have a progressive disease course associated with significant morbidity
and mortality. High-dose cytotoxic therapy followed by autologous stem cell
transplantation has been proposed as a novel treatment for severe autoimmune
diseases. This review will focus on recent advances in the immunopathogenesis of
autoimmunity and will review preliminary results of clinical trials employing
hematopoietic stem cell transplantation for the treatment of autoimmunity.
PMID- 10188072
TI - Reinventing bone marrow transplantation: reducing toxicity using
nonmyeloablative, preparative regimens and induction of graft-versus-malignancy.
AB - Bone marrow transplantation was initially developed as a means to deliver
supralethal doses of chemotherapy and radiation for treatment of malignancies.
Myelosuppression is the dose-limiting toxicity for many chemotherapy drugs and
whole-body radiation. Many malignancies exhibit a steep dose-response
relationship to chemotherapy or radiotherapy. Bone marrow transplantation allows
escalation of doses beyond those levels which produce severe bone marrow
toxicity. Doses of many agents, particularly alkylating agents and whole body
radiation, can be increased three- to fivefold above their conventional maximally
tolerated dose. Marrow transplantation was considered a supportive care modality
to restore hematopoiesis. It has become clear, however, that the high dose
therapy does not eradicate the malignancy in many patients, and that the
therapeutic benefit of allogeneic marrow transplantation is largely related to an
associated immune-mediated graft-versus-malignancy effect.
PMID- 10188073
TI - Lymphoproliferative disorders involving Epstein-Barr virus after hemopoietic stem
cell transplantation.
AB - Lymphoproliferative disorders involving uncontrolled expansion of donor-derived B
cells infected with Epstein-Barr virus (EBV) are a significant problem after
hemopoietic stem cell transplantation. Risk factors, which include T cell
depletion, major histocompatibility complex mismatch, and intensity of
immunosuppression illustrate the importance of T cell immune surveillance. Recent
studies have identified viral and host factors that affect the T-cell response to
EBV. Monitoring EBV load in the blood by polymerase chain reaction allows early
identification of high-risk patients and early institution of therapy. Adoptive
immunotherapy approaches using donor T cells have proven effective and EBV
specific cytotoxic T lymphocytes have also been used successfully for
prophylaxis. The simplest way of preventing EBV lymphoproliferation, however, may
be to deplete B cells from the donor marrow prior to infusion to prevent the
transmission of EBV-infected B cells.
PMID- 10188074
TI - Bone marrow transplantation in multiple myeloma.
AB - Experience from around the world now suggests that high response rates can be
achieved in patients with multiple myeloma treated with high-dose therapy
followed by hematopoietic stem cell transplantation. However, patients are
destined to relapse and few, if any, are cured. Major obstacles to cure are the
excessive toxicity noted after allografting in multiple myeloma, contaminating
tumor cells in multiple myeloma autografts, and most importantly, the persistence
of minimal residual disease after high-dose therapy and either allogeneic or
autologous stem cell transplantation. In this context, strategies are being
developed to decrease the toxicity of allografting and to enhance allogeneic anti
multiple myeloma immunity after transplantation to improve outcome. To improve
autografting, better ablative regimens, more efficacious purging of tumor cells
from autografts, and enhancement of autologous anti-multiple myeloma immunity
post-transplantation are modalities being tested to enhance overall and event
free survival.
PMID- 10188075
TI - Drug resistance in lung cancer.
AB - The major problem in lung cancer chemotherapy is the emergence of inherent and
acquired drug resistance of the cancer cells. Establishment of drug-resistant
sublines and comparative investigations of such cell lines with their parental
cells to determine their molecular, biologic, and biochemical properties are
important research strategies. Genetic changes in tumor cells may induce changes
in their biochemical properties and chemosensitivity. Many mechanisms that render
tumor cells resistant have been identified, and they have provided new molecular
targets for surrogate markers to predict chemosensitivity. The new categories of
anticancer drugs, such as topoisomerase I inhibitors and taxanes, and non
cytotoxic new drugs, have been introduced clinically. It is important to define
the molecular determinants of resistance to these drugs. The development of an
appropriate model for overcoming drug resistance is one of the important issues
that should be solved before carrying out further clinical trials.
PMID- 10188076
TI - Autocrine loops, signal transduction, and cell cycle abnormalities in the
molecular biology of lung cancer.
AB - Lung cancers produce a variety of mitogenic neuropeptides and growth factors and
express receptors for these signaling peptides leading to autocrine and paracrine
loops that stimulate tumor cell proliferation and migration and promote
neovascularization. The effects of these autocrine and paracrine factors are
mediated by a variety of intracellular signal transduction pathways that
ultimately converge on the regulation of cell cycle proteins whose expression and
activity are abnormal in lung cancer cells. During the past year, further
advances have been made in unraveling autocrine loops, signal transduction
pathways, and cell cycle abnormalities in both small cell lung carcinoma (SCLC)
and in non-SCLC. In addition, the hunt for novel tumor suppressor genes has
continued. As our understanding of the fundamental cell and molecular biology of
lung cancer increases, novel possibilities for translational research are
emerging for improving the diagnosis, prognosis, and treatment of the disease.
PMID- 10188077
TI - The role of screening in the management of skin cancer.
AB - The incidence of skin cancer has been rising at an alarming rate for the past
several years. This poses a significant public health problem in the United
States. Detection and treatment of melanoma early in its course is critical for
improved outcome. Of the approaches to cancer control that can reduce mortality
from melanoma and nonmelanoma skin cancer, screening holds the greatest promise
for a rapid and major impact. Prevention and early detection are crucial in
reducing morbidity and mortality from skin cancer. For a number of reasons,
however, the full effect of screening for both melanoma and nonmelanoma skin
cancers has not been achieved. Controversy exists regarding who should perform
screening, who should be screened, and whether screening should be performed at
all. It is clear that melanoma and nonmelanoma skin cancer control programs
combining primary prevention, education, and screening are in developmental
stages. This review will discuss the advantages and disadvantages of screening
for skin cancer.
PMID- 10188078
TI - Pregnancy and exogenous hormones in patients with cutaneous malignant melanoma.
AB - In this article, recent literature is reviewed with regard to possible hormonal
influences on susceptibility to melanoma and prognosis once melanoma is
developed. At the present time, there is little data to suggest that melanoma and
pregnancy interact as far as prognosis is concerned for patients with stage 1 and
stage 2 disease. Recent data have provided further reassurance that oral
contraceptives are safe for patients who have had melanoma, and more data is
required before a definitive statement can be made regarding hormone replacement
therapy for women who have had stage 1 or 2 melanoma adequately treated.
PMID- 10188079
TI - Genetic predisposition to skin cancer.
AB - Here we review recent insights in the genetics of skin cancer susceptibility as
gleaned from studies of three hereditary syndromes: basal cell nevus syndrome,
familial melanoma/dysplastic nevus syndrome, and xeroderma pigmentosum. We
provide a brief synopsis of the recent findings related to these syndromes in an
attempt to illustrate several emerging themes in the genetics of skin cancer.
These themes include 1) the recent identification of multiple cancer
susceptibility genes that occur in a myriad of cellular regulatory pathways; 2)
the relative specificity of certain regulatory pathways to the development of
specific types of cancer; and 3) the important role of DNA damage caused by
ultraviolet radiation and defective DNA repair mechanisms in the development of
skin cancer. We also review the implications of this knowledge to clinical
practice relative to risk assessment, primary prevention, and therapy.
PMID- 10188081
TI - Bibliography. Current world literature. Transplantation.
PMID- 10188080
TI - Cutaneous manifestations of cancer.
AB - The appearance of skin lesions in patients with occult or obvious malignancy may
be of extreme value in the detection and management of cancer because the skin is
readily accessible to examination and biopsy. Examination of the skin of our
patients can provide important insights into underlying malignant processes or
possible complications from cancer treatment. The range of cutaneous
abnormalities is wide, and include cutaneous paraneoplastic syndromes such as
xanthomas, acanthosis nigricans, carcinoid syndrome, unusual erythematous
eruptions such as erythema gyratum repens, and a number of genetic syndromes
associated with malignancies and inherited dermatoses.
PMID- 10188082
TI - Bibliography. Current world literature. Lung and mediastinum.
PMID- 10188083
TI - Bibliography. Current world literature. Melanoma and other skin neoplasms.
PMID- 10188084
TI - [Fine structure of the energy profile of nucleosomal DNA bending rigidity].
PMID- 10188085
TI - [Selection of thyroxin-binding oligodeoxyribonucleotides].
PMID- 10188086
TI - [Mechanism of competitive and noncompetitive inhibition of cholinesterases of
various origin].
PMID- 10188087
TI - [Grey (Halcichoerus grypus) and common (Phoca vitulina) seals in Murman:
adaptation to ice and ecological differentiation in subpopulations].
PMID- 10188088
TI - [The evidence of close phylogenetic relationship between Gliridae and Sciuridae
families based on the study of short retroposon B1-dID].
PMID- 10188089
TI - [Divergent populations od Saccharomyces paradoxus in Hawaii: species in statu
nascendi].
PMID- 10188090
TI - [Ability of a heat-denatured moist globular protein to be renatured upon
dissolution].
PMID- 10188091
TI - [Suppression of the intracellular concentration of ATP by irradiating with a
laser pulse of wavelength lambda=820 nm].
PMID- 10188092
TI - [The process of active dissociation of noncovalently bound substances from DNA in
human cells by flow cytometry].
PMID- 10188093
TI - [Localization of nonproliferating cells in migrating keratinocyte colonies].
PMID- 10188094
TI - [Proliferating effect of cytochrome P-450 inducers in cultured hepatoma cells,
expressing and not expressing cytochrome P-450].
PMID- 10188095
TI - [Effect of heat shock on translation in cell culture].
PMID- 10188096
TI - [A new pathway for regulating purine biosynthesis in Escherichia coli by a
protein-component of the ribose transporter].
PMID- 10188097
TI - [Concentration of mRNA of alpha-2A-adrenergic receptors and the number of
specific binding sites for their agonists in regions of the brain].
PMID- 10188098
TI - [Biogeography and taxonometric diversity of shrews of northeastern Asia].
PMID- 10188099
TI - [Dogs recognize distinctive chromosomal forms of Arvalis and Obscurus common
voles (microtus arvalis Pallas, 1779) and individuals of the same type from
diverse populations by smell].
PMID- 10188100
TI - [Effect of high molecular weight polymers on blood circulation: perfusion
experiments].
PMID- 10188101
TI - [Recognition of visual patterns during musical accompaniment].
PMID- 10188102
TI - [Mauthner neurons of fish as a test system for screening the Arthropod venoms].
PMID- 10188103
TI - [Protein synthesis in blood lymphocytes of patients with rheumatoid arthritis].
PMID- 10188104
TI - [Saltation changes in the structure of ribosomal gene clusters during evolution
of cockroaches of Blattella genus].
PMID- 10188105
TI - Relationship between enzymatic markers of pulmonary cell damage and cellular
profile: a study in bronchoalveolar lavage fluid.
AB - It has been suggested that alterations in bronchoalveolar lavage fluid (BALF)
reflect pathologic changes in the lung. Cytoplasmatic enzymes such as lactate
dehydrogenase (LDH), alkaline phosphatase (ALP), and LDH isoenzymes are
recognized indicators of cell damage or death. The aim of this study was to
determine whether there is a relation between the enzyme activity and the cell
types present in BALF. Therefore, BALF samples obtained from patients with
various pulmonary disorders were studied. Out of these samples a group with
mainly polymorphonuclear neutrophils (PMNs; n = 15; Group I) and another with
mainly alveolar macrophages (AMs; n = 10; Group II) were selected. Additionally,
the value of analysis of lysed cells in BALF for assessment of LDH-isoenzyme
patterns was examined. The cell-free fraction of BALF of Group II showed lower
LDH and ALP activity compared to Group I. The LDH-isoenzyme pattern also
differed, with the LDH3/LDH5 ratios being lower in all BALF samples with
predominantly PMNs than in BALF samples with predominantly AMs. Lysis of the
cells present in the BALF samples by sonication prior to LDH-isoenzyme analysis
provided no additional information beyond that found by analysis of the cell-free
BALF. In conclusion, determination of enzyme activity appears to be useful in
monitoring pulmonary inflammation.
PMID- 10188106
TI - A new methodology for controlled particle inhalation by small rodents.
AB - In order to investigate the deposition, retention, and clearance mechanisms
implicated in particle inhalation under standardized conditions, we developed a
continuous negative-pressure ventilation system, whereby the breathing pattern in
small rodents could be controlled during exposure to aerosols. Using an on-line
open-flow set-up, 19 anesthetized, intubated, and paralyzed Syrian golden
hamsters, individually contained within a whole-body box, were artificially
ventilated under the said continuous negative-pressure conditions, 1 of 5
different combinations of breathing frequency and tidal volume being established.
The animals were then exposed to aerosols containing 6-micron diameter
polystyrene spheres, and the deposition of particles in the conducting airways
was monitored photometrically. During exposure, the level of respiration (mean
lung inflation) was stabilized by means of a negative-pressure vent. Breathing
frequency and tidal volume, as well as the compliance of the system, remained
virtually unchanged during the course of a single experiment, and in each case, a
reproducible deposition of particles was achieved. Our findings indicate that
tidal volume, but not breathing frequency, has a marked influence on the particle
deposition ratio. Breathing frequency exerts opposing and counterbalancing
effects on this latter parameter by enhancing the impaction of particles on the
one hand, and by decreasing sedimentation on the other.
PMID- 10188107
TI - An examination of the different variables affecting surfactant aggregate
conversion in vitro.
AB - Pulmonary surfactant exists in 2 major subtypes, the freshly secreted, surface
active large surfactant aggregates (LA) and their metabolic product, the less
surface active, small aggregates (SA). Conversion of LA into SA can be studied
using an in vitro technique, surface area cycling, which involves the rotation of
a suspension of LA end-over-end so that the surface area of the liquid changes
twice each cycle. In order to further elucidate the mechanisms involved in
aggregate conversion, we have examined the effects of time, temperature, change
in surface area, cycling speed, surfactant concentration, and albumin on
aggregate conversion in vitro. Three different surfactant preparations were used;
rabbit LA, sheep LA, and an exogenous surfactant preparation, bovine lipid
extract surfactant (BLES). Based on our results that showed that these variables
affected aggregate conversion, we concluded that the adsorption of surfactant at
the changing air-liquid interface was an important step in aggregate conversion.
However, the results also indicated that aggregate conversion was not solely due
to the adsorption characteristics of the surfactant. Other surfactant properties,
such as the activity of serine protease or film stability at the air-liquid
interface, may also be important in aggregate conversion.
PMID- 10188108
TI - Plasmacytoid monocytes appear in the bronchoalveolar lavage: differences between
smokers and nonsmokers.
AB - The primary purpose of this study was to describe the expression pattern of the
surface antigens CD68, CD36, 27E10, G16/1, and RM3/1 on bronchoalveolar lavage
(BAL) cells of smokers and nonsmokers. We found a cell type, morphologically
similar to lymphocytes, which showed a strong expression of the monocyte markers
CD68 and CD36. We therefore recognized these cells as plasmacytoid monocytes
(PM). Hereby we report the appearance of PM in the BAL and its dependency of
smoking. The study was conducted in 40 patients with various lung diseases and
normal subjects. Sixteen patients and normal subjects were smokers and 24 were
nonsmokers. There was a significant increase of PM in the BAL of smokers compared
to nonsmokers. However we could not find a disease-related increase of PM in the
BAL. This is the first report demonstrating the occurrence of PM in the BAL. Our
data support the monocytic origin of PM and suggest an involvement in T cell
mediated responses of the lung.
PMID- 10188109
TI - Regulation of human lung fibroblast C1q-receptors by transforming growth factor
beta and tumor necrosis factor-alpha.
AB - Transforming growth factor-beta (TGF-beta) and tumor necrosis factor-alpha (TNF
alpha) are two polypeptide mediators which are believed to play a role in the
evolution of idiopathic pulmonary fibrosis (IPF). We have evaluated the effect of
these two substances on the expression of receptors for collagen (cC1q-R) and
globular (gC1q-R) domains of C1q and on type I collagen in human lung
fibroblasts. Two fibroblast subpopulations differing in C1q receptor expression
were obtained by culturing human lung explants in medium containing fresh human
serum and heated plasma-derived serum and separating them based on C1q binding
[Narayanan, Lurton and Raghu: Am J Resp Cell Mol Biol. 1998; 17:84]. The cells,
referred to as HH and NL cells, respectively, were exposed to TGF-beta and TNF
alpha in serum-free conditions. The levels of mRNA were assessed by in situ
hybridization and Northern analysis, and protein levels compared after SDS
polyacrylamide gel electrophoresis and Western blotting. NL cells exposed to TGF
beta and TNF-alpha contained 1.4 and 1.6 times as much cC1q-R mRNA, respectively,
whereas in HH cells cC1q-R mRNA increased 2.0- and 2.4-fold. The gC1q-R mRNA
levels increased to a lesser extent in both cells. These increases were not
reflected in protein levels of CC1q-R and gC1q-R, which were similar to or less
than controls. Both TGF-beta and TNF-alpha also increased procollagen [I] mRNA
levels in both cells. Overall, TNF-alpha caused a greater increase and the degree
of response by HH fibroblasts to both TGF-beta and TNF-alpha was higher than NL
cells. These results indicated that TGF-beta and TNF-alpha upregulate the mRNA
levels for cC1q-R and collagen and that they do not affect gC1q-R mRNA levels
significantly. They also indicated different subsets of human lung fibroblasts
respond differently to inflammatory mediators.
PMID- 10188111
TI - Incidence of the concrete scalp deformity associated with deep scalp donor sites
and management with the Unna cap.
AB - The scalp has become a popular donor site for split-thickness skin grafts. This
donor site does, however, have complications, including the concrete scalp
deformity, which consists of hairs embedded in a thick, desiccated, exudative
crust. This article presents our burn unit's experience with this complication.
Fifty-six patients underwent scalp skin graft harvesting between 1984 and 1996.
All grafts were quite thick and were used for resurfacing facial burns. Thirty
eight donor sites were treated with medicated gauze, and 18 were treated with the
Unna cap, which is an Unna dressing applied over Aquaphor gauze (Beiersdorf,
Norwalk, Conn). Eighteen of the 38 patients (32%) treated with medicated gauze
developed the concrete scalp deformity. None of the patients treated with the
Unna cap developed the deformity. Although useful, the deep scalp donor site has
complications, including the concrete scalp deformity. However, with use of the
Unna cap dressing, we have had no occurrences of this problem.
PMID- 10188110
TI - Manipulation of injury and repair of the alveolar epithelium using two
pneumotoxicants: 3-methylindole and monocrotaline.
AB - The role of type II epithelial cell proliferation in repair of diffuse alveolar
epithelial injury was examined using two pneumotoxicants, 3-methylindole (3-MI)
and monocrotaline (MCT). It was hypothesized that if MCT inhibits type II
epithelial cell mitosis, then pulmonary fibrosis would result after diffuse 3-MI
induced type I alveolar cell injury in rats preadministered MCT. Four groups of
rats were given vehicle control, MCT, 3-MI, or MCT and 3-MI. Lungs from rats
killed 4 days post-treatment were examined subjectively and quantitatively by
light and electron microscopy. Proliferative stimulus was estimated by
bromodeoxyuridine (BrdU) incorporation. Lungs from rats killed 2 weeks post
treatment were evaluated by light microscopy. At 4 days, the number of type II
cells in the lungs of 3-MI-treated rats was 3 times greater than in the lungs of
the dually (MCT/3-MI) treated rats which was the same as the control rat lungs.
There was no significant difference between the MCT/3-MI-treated rats and the 3
MI-treated rats with regard to the percentage of denuded alveolar basement
membrane. The number of BrdU-labeled type II epithelial cells was increased above
the control in both 3-MI-treated groups, but was greater in the 3-MI-treated rat
lungs than in the lungs of the MCT/3-MI-treated rats. The average type II cell
volume in dually treated rats was 3 times the volume in the control animals and
50% greater than that in 3-MI-treated rats. Transmission electron microscopy of
the lungs of the MCT/3-MI-treated rats demonstrated flattened hypertrophic type
II cells over large portions of the basement membrane. The light microscopic
appearance and collagen staining of the lungs of the dually treated rats were
similar to the negative control rat lungs 2 weeks after dosing with 3-MI. This
suggests that despite a proliferative stimulus, MCT inhibits type II cell
division after diffuse alveolar type I cell injury, but that type II cell
migration and coverage of the basal lamina proceed. Results of this study suggest
that coverage of the denuded basal lamina by any method is sufficient to prevent
interstitial alveolar fibrosis.
PMID- 10188112
TI - Pediatric burn patients with respiratory failure: predictors of outcome with the
use of extracorporeal life support.
AB - Extracorporeal life support (ECLS) for pediatric burn patients is a viable option
for respiratory failure that is unresponsive to maximal conventional therapy. No
criteria have been identified that are predictive of the success of the use of
ECLS for these patients. This article presents a retrospective review of the
pediatric burn patients placed on ECLS at a single pediatric medical center. It
was found that 12 patients (mean age, 30.3 months; range 6 to 69 months) were
placed on ECLS because of profound pulmonary failure that was unresponsive to
aggressive ventilatory support. The mean size of the burns of these patients was
50.2% of the total body surface area (average size of full-thickness burns, 41.8%
total body surface area), with 6 patients having scald burns and 6 having flame
burns. The overall survival was 67% (8 of 12). Nonsurvivors had greater positive
end-expiratory pressure, mean airway pressure, peak inspiratory pressure, and
oxygenation index before ECLS. It is felt that ECLS is a life-saving therapy for
pediatric patients with thermal injury. Greater ventilator requirements before
ECLS are associated with nonsurvival. Early institution of ECLS in pediatric burn
patients with severe respiratory failure may prevent excessive barotrauma and
thus discourage the onset of irreversible lung injury.
PMID- 10188113
TI - Lorazepam given the night before surgery reduces preoperative anxiety in children
undergoing reconstructive burn surgery.
AB - A high level of preoperative anxiety frequently occurs in children undergoing
reconstructive burn surgery. Reduction of this anxiety may have a number of
physiological and psychological benefits. Various pharmaceutical and
nonpharmaceutical regimens to reduce preoperative anxiety have been devised;
however, most regimens are not initiated until the period immediately before
surgery. Many of the children in our institution report high levels of anxiety
beginning the night before surgery. Therefore we hypothesized that sedation the
night before surgery would be beneficial. Oral lorazepam 0.025 mg/kg or placebo
was given the night before surgery to 45 patients in a prospective, randomized,
double-blind fashion; in addition, all patients received preoperative sedation
per protocol on the day of surgery. Immediately before induction of anesthesia,
all patients (mean age 12.5 +/- 0.9 years, range 6 to 18 years) performed an
anxiety self-rating with the use of a validated visual analog scale (VAS).
Patient anxiety and quality of anesthesia induction was also rated by one of the
investigators. Postoperatively, patients rated their recall of anxiety with the
use of the VAS. When queried preoperatively, patients who received lorazepam the
night before surgery self-reported significantly less anxiety than those
receiving placebo. Investigator observations did not detect this difference; this
reinforces the assertion that patient self-rating of anxiety may be the best tool
for rating anxiety.
PMID- 10188114
TI - Topical application of yeast extract accelerates the wound healing of diabetic
mice.
AB - Alcoholic extracts of yeast have been used as the active ingredient in
medications under names such as "tissue or skin respiratory factor," Biodyne
(Sperti Drug Co, Cincinnati, Ohio--now defunct), and live yeast cell derivative
(LYCD). Beneficial clinical results from the use of LYCD have been reported for
the treatment of burns, wounds, and hemorrhoids. The medicinal effects of LYCD
have recently been localized to a protein fraction containing a mixture of
several peptides. The effects of topical application of the peptide mixture on
wounds were examined in diabetic mice, an animal model in which the healing
process is disrupted and delayed. Full-thickness wounds were created on the backs
of diabetic (DB) and nondiabetic (non-DB) mice. Half of the DB and non-DB mice
were treated with 0.05 mL of LYCD after wounding and for 4 successive days. All
other mice received vehicle. Wound areas were measured at Day 0 and at 2-day
intervals. Mice were sacrificed at 3, 7, 10, 21, and 28 days postinjury.
Differences in the extent and quality of healing appeared between DB mice
receiving LYCD and DB mice receiving vehicle by day 10 (P < .0001). By 24 days
postinjury, DB mice receiving LYCD had achieved 100% wound closure, whereas DB
mice receiving vehicle had achieved only 31.4% wound closure. Histologic
examination of wounds reflected improved wound healing in DB mice receiving LYCD
as compared with those receiving vehicle. A topically applied yeast extract
peptide mixture significantly attenuates wound closure and the degree of cellular
reorganization of full-thickness excisional wounds of DB mice.
PMID- 10188115
TI - New assistive technology for passive standing.
AB - The anesthetic skin of patients with spinal cord injuries makes these patients a
high-risk population for burn injuries. Innovations in rehabilitation engineering
can now provide the disabled with mechanical devices that allow for passive
standing. Passive standing has been shown to counteract many of the effects of
chronic immobilization and spinal cord injury, including bone demineralization,
urinary calculi, cardiovascular instability, and reduced joint range of motion
and muscular tone. This article will describe several unique assistive devices
that allow for passive standing and an improvement in daily living for people
with disabilities.
PMID- 10188116
TI - The physical, functional, and developmental outcome of pediatric burn survivors
from 1 to 12 months postinjury.
AB - Fifty-one children with an average age of 27 months and who had sustained a burn
injury were tested at 1, 6, and 12 months postinjury to determine their physical,
functional, and developmental outcomes. Most parents were either African-American
or Hispanic, lived on public assistance, and had a high school education or less.
Most children had normal range of motion and were appropriate for their age in
self-care skills. On the basis of the Home Screening Questionnaire, 48% of the
children came from suspect home environments. Developmental delays were noted in
language acquisition that persisted over the first year postburn. Although the
outcomes of these burn injuries were good in physical and functional areas, the
developmental findings raised concerns. The results alert clinicians to screen
for potential developmental problems during the burned child's recovery phase and
to include appropriate developmental activities and parental guidance in the
treatment plan.
PMID- 10188117
TI - BurnWare: National Tracs/ABA computer use in the burn center. A review of
reviews.
PMID- 10188118
TI - The Unna "cap" as a scalp donor site dressing.
AB - Deep scalp donor sites can be difficult to manage because of the higher incidence
of healing complications that can make daily wound care exquisitely painful. When
faced with this problem, we prospectively studied the Unna "cap" dressing on the
scalp. Group 1 received our standard treatment--Xeroform gauze (Sherwood Medical,
St Louis, Mo) and daily wound care. Group 2 received the Unna cap--Aquaphor gauze
(Beiersdorf, Norwalk, Conn) and Dome Paste gauze (Bayer Corp, West Haven, Conn)
with wound care every 3 days. Pain, healing time, and costs were compared. Twelve
patients between the age of 1 and 54 years were studied. A significant number of
patients in Group 1 developed wound complications after initial healing,
resulting in a longer length of stay and higher costs. Group 2 reported
significantly less procedural pain, comparable healing (11 days +/- 2 SD), and
fewer dressing changes, resulting in an institutional savings of $5.51 to $16.25
per patient up to postoperative day 13. This study supports use of the Unna cap
as a less painful, safe, and cost-effective alternative to our standard deep
scalp donor site dressing.
PMID- 10188119
TI - Self-inflicted burn injuries: an 11-year retrospective study.
AB - The burns unit at the Royal Brisbane Hospital accepted a total of 2275 admissions
from 1986 to 1996. During this 11-year period, 65 cases of self-inflicted burn
injury were treated, which made up 2.9% of the total number of admissions. A
mortality rate of 21.5% (14 patients) is noted, with all patients dying after
admission to the hospital. A common feature of people that self-inflict burn
injuries is a psychiatric history, with many patients having histories of self
harm or suicide attempts. Two distinct groups were identified--those with
suicidal intent and those with intent of self-harm. Those patients with self
inflicted injuries have an increased mean of 31.4% total body surface area burned
as compared with those patients whose injuries are accounted for as accidental,
which have a mean total body surface area burned of 10%. Additionally, the mean
length of stay in the hospital for patients with self-inflicted injuries was 40
days for acute injuries, which is prolonged; the mean length of stay for acute
injuries that were not self-inflicted was 14 days. This investigation discovered
3 cases of repeated self-inflicted burn injury.
PMID- 10188120
TI - The Le Fort I osteotomy as a surgical approach for removal of tumours of the
midface.
AB - Tumours of the midface and maxillary sinuses have been removed via multiple
approaches. The most common approaches are those using incisions in the facial
skin, especially in the case of malignant tumours. The Le Fort I procedure via an
intraoral incision as described by Sailer in 1986 is a versatile alternative.
Combined with a coronal approach and various osteotomies of the upper face it
also allows removal of tumours extending into the orbits, the nasoethmoidal
complex and the skull base. The versatility of the Le Fort I osteotomy as a
surgical approach was analysed in 17 cases. This method is reliable and gives
excellent access. Further advantages are the wide surgical exposure and the clear
visibility of the resection margins, the absence of visible scars, the
feasibility of combining this approach with reconstruction using the buccal fat
pad and the possibility of simultaneous placement of bone grafts, insertion of
endosseous implants or other preprosthetic procedures via the same incision.
PMID- 10188121
TI - Orbital and globe rotation: the role of the periorbita.
AB - We hypothesize that excyclorotation of the globe and extraocular muscle cone
associated with external orbital rotation around each orbital axis in
craniofacial conditions could be at least partially corrected by leaving the
anterior periorbita (periosteum lining the orbit) attached to the surgically
rotated portion of the orbit. This hypothesis was tested by comparing the degree
of rotation of the globe in response to internal rotation of the anterior orbit,
leaving the periorbita attached to the rotated portion of the orbit on one
(study) side, and stripping the periorbita on the opposite (control) side, in
nine fresh cadavers. There was a highly significant difference (P < 0.0001)
between the study and control sides. The possible extrapolations of this finding
to the clinical situation are discussed.
PMID- 10188122
TI - A surgical method for treating anterior skull base injuries.
AB - Skull base surgery was performed on 18 patients with anterior skull base
injuries. The operative technique consisted of opening the operative field in the
anterior skull base via a coronal incision and a frontal craniotomy, debridement
of the anterior skull base including the injured dura mater, performing drainage
from the anterior skull base to the nasal cavity by ethmoidectomy, and
reconstructing the resulting dural and anterior skull base defect using bilateral
temporal musculo-pericranial flaps and a bone graft. Seventeen of the 18 patients
recovered without any complications, although epidural abscesses in the anterior
skull base had been present in four patients at the time of the operation. Only
one patient developed an epidural abscess in the anterior skull base after the
operation. None of the patients developed any other complications including
meningitis, recurrent liquorrhoea or cerebral herniation. Satisfactory aesthetic
results were achieved in 16 of the 18 patients. In one patient, uneven deformity
of the forehead, which was caused by the partial sequestration of the frontal
bone due to postoperative infection, was observed. In another patient, a
depressed deformity of the forehead, which was caused by the partial loss of the
frontalis muscle following the use of the frontal musculo-pericranial flap
instead of a temporal musculo-pericranial flap, was observed. Anterior skull base
reconstruction using bilateral temporal musculo-pericranial flaps provides
excellent results in terms of patient recovery and aesthetics.
PMID- 10188123
TI - Frontal sinus fractures: computed tomography evaluation of sinus obliteration
with lyophilized cartilage.
AB - Allogenic lyophilized cartilage has been proven clinically to be a reliable
material for obliteration of the frontal sinus without the limitations of donor
site morbidity and the prolongation of the operation time produced by autogenic
grafting. The long-term behaviour of the implanted material is of paramount
importance for the success of the obliterative technique. This survey included 51
trauma patients on whom obliteration of the frontal sinus with lyophilized
cartilage was performed. The fate of the lyophilized cartilage graft was
evaluated from computed tomography imaging of the obliterated frontal sinus. No
radiological sign of mucocele formation or inflammatory disease was noted. Bone
density measurement of the obliterated sinus and the adjacent trabecular bone was
calculated. The patient population was distributed into four groups (0-2, 2-4, 4
6, > 6 years) according the postobliterative time. The bone density of the
implanted lyophilized cartilage was accentuated from group 1 to group 4 when
compared with the bone density of the trabecular bone. This shows the long-term
tendency of lyophilized cartilage graft to osseous substitution.
PMID- 10188124
TI - Marcus Gunn Jaw-Winking Phenomenon: management and results of treatment in 19
patients.
AB - From 1980-1995, 19 patients displaying the Marcus Gunn Phenomenon (MGP) were
treated in the Department of Maxillofacial Surgery of the Jagiellonian University
in Krakow, Poland. Sixteen patients were operated on according to the Neuhaus
method, in one case bilaterally. In three patients, the upper eyelid, after
partial transsection of the levator muscle, was suspended from the frontal muscle
on autogenous temporal fascia strips. At postoperative follow-up, the width and
symmetry of the palpebral fissures were evaluated as well as persistent symptoms
of synkinetic eyelid movement. In 13 (68.4%) patients, proper width and symmetry
of the palpebral fissures were obtained, whereas in the remaining six (36.1%)
marked improvement and decreased asymmetry of palpebral fissures were achieved.
Pathological synkinesis disappeared totally in 16 (84.2%) of the patients on
operated.
PMID- 10188125
TI - Stereolithographic biomodelling in cranio-maxillofacial surgery: a prospective
trial.
AB - Stereolithographic (SL) biomodelling is a new technology that allows three
dimensional (3-D) computed tomography (CT) data to be used to manufacture solid
plastic replicas of anatomical structures (biomodels). A prospective trial with
the objective of assessing the utility of biomodelling in complex surgery has
been performed. Forty-five patients with craniofacial, maxillofacial, skull base
cervical spinal pathology were selected. 3-D CT or MR scanning was performed and
the data of interest were edited and converted into a form acceptable to the
rapid prototyping technology SL. The data were used to guide a laser to
selectively polymerize photosensitive resin to manufacture biomodels. The
biomodels were used by surgeons for patient education, diagnosis and operative
planning. An assessment protocol was used to test the hypothesis that 'biomodels
in addition to standard imaging had greater utility in the surgery performed than
the standard imaging alone'. Biomodels significantly improved operative planning
(images 44.09%, images with biomodel 82.21%, P < .01) and diagnosis (images
65.63%, images with biomodel 95.23%, P < .01). Biomodels were found to improve
measurement accuracy significantly (image measurement error 44.14%, biomodel
measurement error 7.91%, P < .05). Surgeons estimated that the use of biomodels
reduced operating time by a mean of 17.63% and were cost effective at a mean
price of $1031 AUS. Patients found the biomodels to be helpful for informed
consent (images 63.53%, biomodels 88.54%, P < .001). Biomodelling is an
intuitive, user-friendly technology that facilitated diagnosis and operative
planning. Biomodels allowed surgeons to rehearse procedures readily and improved
communication between colleagues and patients.
PMID- 10188126
TI - Rehabilitation with dental implants of oral cancer patients.
AB - The aim of this study was to evaluate the risks and complications of
rehabilitation with dental implants after tumour surgery and radiotherapy. After
a disease-free survival of 18 months, 29 patients who had undergone oral cancer
treatment were rehabilitated with dental implants. The complication rate of
implants in irradiated, non-irradiated and grafted bone was analyzed at least 3
years after implant placement. In the healing period, 28.6% of the implants in
irradiated bone and 8.4% in non-irradiated bone showed soft tissue complications.
Of the implants, 26.7% in the irradiated and 14.7% in the non-irradiated
mandibular bone were lost in the first 36 months after placement. Thirty-one
point two percent of implants inserted in non-irradiated bone grafts were
affected and did not osseointegrate. Of 109 inserted implants, 70 were suitable
for prosthetic rehabilitation. There are high complication rates after implant
placement in oral cancer patients. Irradiation adversely affects soft tissue
healing. Osseointegration is frequently disturbed, especially when implants were
placed in non-vascularized bone grafts.
PMID- 10188127
TI - SR-PLLA and SR-PGA miniscrews: biodegradation and tissue reactions in the
calvarium and dura mater.
AB - The biocompatibility and degradation of self-reinforced poly-L-lactide (SR-PLLA)
and polyglycolide (SR-PGA) miniscrews, vs titanium miniscrews, was studied in
frontal bone osteotomies in 20 lambs, where they were used for plate fixation. At
follow-up at 4, 6, 12, 26, 52 and 104 weeks, no clinical foreign body reaction,
infection or other complications had occurred. Histologically, PGA material was
hydrolyzed and fragmented at 4-6 weeks and was resorbed by 12 weeks, whereas the
SR-PLLA miniscrews retained their integrity and holding power for 26 weeks and
were mostly resorbed at 2 years. According to histological and histomorphometric
analyses and plain film radiography, the degradation of PGA miniscrews was
accompanied by a typical non-specific foreign-body reaction and initial transient
osteolysis with decreased osteoid formation around the screw channel, but
compensatory intense osteoid formation and bone remodelling followed after
resorption of the polymer. The foreign body reactions to PLLA and titanium were
considerably milder. All miniscrews were commendably strong and could be
satisfactorily tightened against the plate. SR-PLLA miniscrews offer fixation
stability for half a year, whereas rapidly degrading SR-PGA miniscrews may be
used when short-term fixation is needed.
PMID- 10188128
TI - Biodegradable osteosynthesis material for stabilization of midface fractures:
experimental investigation in sheep.
AB - The most frequently tested biodegradable osteosynthesis materials have up to now
largely consisted of poly-L-lactide (PLLA). The PLLA polymers appear to have
sufficient mechanical strength for fracture treatment in the midface, but their
degradation does not seem to be uniform enough to allow their clinical use.
During the degradation process the disintegration products elicit a foreign body
reaction due to non-uniform degradation rates. The foreign body reaction is
sometimes combined with a fluctuant swelling at the implantation site. Implants
injection-moulded from 90:10 PLLA/PGA (polyglycolic acid) have a more uniform
degradation rate and seem to lead to a milder foreign body reaction. We bridged
Le Fort I osteotomies in sheep using a system of injection-moulded PLLA/PGA 90:10
plates and screws and compared it with 2 mm AO miniplates and mini-screws made
from titanium. Light microscopy evaluation showed that the PLLA/PGA copolymer
system experienced its highest mechanical stress at the transition from screw
head to screw shaft. Nevertheless, the fragments fixed with the copolymers were
on the whole only slightly less stable than those fixed with the titanium system.
The foreign body reaction solely due to co-polymer degradation was not severe,
considering the fibrous tissue response that was found associated with the
titanium components. The study does show that the copolymer investigated is
adequate for clinical use as a biodegradable osteosynthesis material, at least in
low stress bearing areas.
PMID- 10188129
TI - The self adapting washer for lag screw fixation of mandibular fractures: finite
element analysis and preclinical evaluation.
AB - Besides rigid fixation, lag screws have distinct advantages compared with plates
in appropriate indications in mandibular fractures. However, in current lag screw
systems, the relatively small area of the screw head has to transfer the tensile
force which can exceed 1000 N in the symphysis, to the thin cortical bone plate.
Countersinking, which is obligatory in most systems, will weaken the cortical
plate. Finite element analysis (FEA) revealed that load in this situation can
exceed the normal tensile strength of metal and bone. Consequently, a new washer
was constructed which both increased the supporting surface and did not require
countersinking. The washer is self adapting (SAW) to the cortical plate in a
defined position, forming a ball and socket joint with the screw head. Using the
FEA model, a ten-fold reduction in load on bone and metal was observed with the
new washer. In a miniature pig mandibular symphysis fracture model, the clinical
applicability and a favourable histological reaction were demonstrated, compared
with conventional lag screw designs.
PMID- 10188130
TI - Time course of sleep inertia dissipation in human performance and alertness.
AB - Alertness and performance on a wide variety of tasks are impaired immediately
upon waking from sleep due to sleep inertia, which has been found to dissipate in
an asymptotic manner following waketime. It has been suggested that behavioural
or environmental factors, as well as sleep stage at awakening, may affect the
severity of sleep inertia. In order to determine the time course of sleep inertia
dissipation under normal entrained conditions, subjective alertness and cognitive
throughput were measured during the first 4 h after habitual waketime from a full
8-h sleep episode on 3 consecutive days. We investigated whether this time course
was affected by either sleep stage at awakening or behavioural/environmental
factors. Sleep inertia dissipated in an asymptotic manner and took 2-4 h to near
the asymptote. Saturating exponential functions fitted the sleep inertia data
well, with time constants of 0.67 h for subjective alertness and 1.17 h for
cognitive performance. Most awakenings occurred out of stage rapid eye movement
(REM), 2 or 1 sleep, and no effect of sleep stage at awakening on either the
severity of sleep inertia or the time course of its dissipation could be
detected. Subjective alertness and cognitive throughput were significantly
impaired upon awakening regardless of whether subjects got out of bed, ate
breakfast, showered and were exposed to ordinary indoor room light (approximately
150 lux) or whether subjects participated in a constant routine (CR) protocol in
which they remained in bed, ate small hourly snacks and were exposed to very dim
light (10-15 lux). These findings allow for the refinement of models of alertness
and performance, and have important implications for the scheduling of work
immediately upon awakening in many occupational settings.
PMID- 10188131
TI - Simple reaction time, duration of driving and sleep deprivation in young versus
old automobile drivers.
AB - Car accidents are one of the major causes of death in modern society and
sleepiness is identified as one major risk factor. The purposes of the present
study were: (1) to relate the sleep loss and driving time to a performance
indicator and (2) to identify risk factors of performance decrement. We
investigated 294 drivers (age < 30 years, n = 100; age > or = 30 years, n = 194)
who drove into a rest stop area. All were asked to fill out a questionnaire about
the drive and previous sleep/wake pattern, and to carry out a 10 min, simple
reaction time (RT) test. The level of performance is identified by the 10%
slowest RTs. Multiple regression analysis, with the mean of the 10% Slowest RTs
as the dependent variable, showed that age, duration of drive, and duration
(shortness) of previous breaks were the main predictors. Our study suggests that
public awareness may need to be raised with respect excessive length of driving,
especially in young drivers.
PMID- 10188132
TI - Eastward long distance flights, sleep and wake patterns in air crews in
connection with a two-day layover.
AB - The present study describes the spontaneous sleep/wake pattern in connection with
an eastward (Stockholm to Tokyo, +8 h) transmeridian flight and short (51 h)
layovers. To describe all sleep episodes and the recovery process across 4 days,
and to relate adjustment to individual differences, 49 Scandinavian Airlines
System (SAS) air crew were monitored for 9 days with activity monitors and
sleep/wake diary before-during-after flight. The outbound flight involved a
period of wakefulness extended to 21 h, frequently (87% of air crew) terminated
by a long nap in Tokyo which was calm but difficult to wake up from. Then
followed two night oriented sleep periods of normal length but of reduced
efficiency, containing many and long awakenings. Napping was common during the
extended periods of wakefulness, particularly during flights. During the recovery
days, ease of rising from sleep in the mornings was difficult throughout, and
feelings of not being refreshed returned to baseline levels on the third recovery
sleep. Elevated daytime sleepiness (24% of the day) was observed on the first
recovery day. No individual differences related to gender, age or position
(cabin/pilot) was found in sleep strategy. Poor adjusters, subjects with a
perceived lowered capacity on recovery days, showed more premature awakenings
abroad and less refreshing sleep during the last 12 months, suggesting a
decreased ability to cope with air crew scheduling. Comparisons with a westbound
flight showed the eastbound flight layover sleep to be more problematic and
containing more napping.
PMID- 10188133
TI - Modelling and exploring human sleep with event history analysis.
AB - In this paper we propose the use of statistical models of event history analysis
for investigating human sleep. These models provide appropriate tools for
statistical evaluation when sleep data are recorded continuously over time or on
a fine time grid, and are classified into sleep stages such as REM and nonREM as
defined by Rechtschaffen and Kales (1968). In contrast to conventional
statistical procedures, event history analysis makes full use of the information
contained in sleep data, and can therefore provide new insights into non
stationary properties of sleep. Probabilities of or intensities for transitions
between sleep stages are the basic quantities for characterising sleep processes.
The statistical methods of event history analysis aim at modelling and estimating
these intensities as functions of time, taking into account individual sleep
history and assessing the influence of factors of interest, such as hormonal
secretion. In this study we suggest the use of non-parametric approaches to
reveal unknown functional forms of transition intensities and to explore time
varying and non-stationary effects. We then apply these techniques in a study of
30 healthy male volunteers to assess the mean population intensity and the
effects of plasma cortisol concentration on the transition between selected sleep
stages as well as the influence of elapsed time in a current REM period on the
intensity for a transition to nonREM. The most interesting findings are that (a)
the intensity of the nonREM-to-REM transitions after sleep onset in young men
shows a periodicity which is similar to that of nonREM/REM cycles; (b) 30-45 min
after sleep onset, young men reveal a great propensity to pass from light sleep
(stages 1 or 2) into slow-wave sleep (SWS) (stages 3 or 4); (c) high cortisol
levels imposed additional impulses on the transition intensity of (i) wake to
sleep around 2 h after sleep onset, (ii) nonREM to REM around 6 h later, (iii)
stage 1 or stage 2 sleep to SWS around 2, 4 and 6 h later and (iv) SWS to stage 1
or stage 2 sleep about 2 h later. Moreover, high cortisol concentrations at the
beginning of REM periods favoured the change to nonREM sleep, whereas later their
influence on a nonREM change became weak and weaker. As sleep data are also
available as event-oriented data in many studies in sleep research, event history
analysis applied additionally to conventional statistical procedures, such as
regression analysis or analysis of variance, could help to acquire more
information and knowledge about the mechanisms behind the sleep process.
PMID- 10188134
TI - Heart period and heart period variability during sleep on the MIR space station.
AB - The long-term acclimation of cardiac rhythms to microgravity was studied in four
astronauts aboard the Russian space station MIR during wakefulness and sleep.
Sleep polygraphies were obtained between the third and the 30th day in space and,
in addition, prior to mission on the ground. From each of the sleep polygraphies,
beat-to-beat intervals of cardiac rhythms were determined. The response of heart
period and heart period variability to the stimulus microgravity was tested
during sleep across sleep stages and during waking. A lengthening of heart period
by about 100 ms was found in space compared to measurements on the ground. The
slowing of heart rate was more pronounced for non-REM sleep than for REM sleep. A
systematic change in heart period in relation to the duration of the stay in
space could not be detected. An analysis of heart period variability in the high
frequency (respiratory sinus arrhythmia) band supports the hypothesis that the
decrease of heart rate under microgravity is produced by an increase in
parasympathetic activity. Testing the response of cardiac rhythms to microgravity
across distinct behavioural states seems to be a powerful tool to investigate the
cardiovascular system.
PMID- 10188135
TI - Sino-aortic denervation augments the increase in blood pressure seen during
paradoxical sleep in the rat.
AB - Using a computer assisted telemetric system, we have re-examined the effect of
sino-aortic denervation (SAD) on the changes in arterial blood pressure (AP) and
heart rate (HR) during sleep in the rat suitably recovered from the operation.
Eight 1 hourly polygraphic recordings were performed 4 weeks after the initial
SAD surgery. In the SAD rats, the increase in AP during paradoxical sleep (PS)
was much larger than that in sham-operated rats. HR in the SAD rats increased on
going from slow-wave sleep to PS, but it showed no change in sham-operated rats.
The present study suggests that chronic SAD causes the enhanced AP increase
during PS concomitantly with the persistent hypertension and tachycardia across
sleep-wake states.
PMID- 10188137
TI - The relationship between 6-sulphatoxymelatonin and polysomnographic sleep in good
sleeping controls and wake maintenance insomniacs, aged 55-80 years.
AB - The pineal hormone, melatonin, is reported to possess hypnotic properties. This
has led to an investigation of the relationship between the endogenous melatonin
rhythm and sleep. However, this relationship has yet to be fully examined in aged
insomniacs and controls. From media advertisements, 16 good sleeping controls
(11F, 5M) and 16 sleep maintenance insomniacs (11F, 5M), aged over 55 years, were
recruited to participate in a study involving four nights of polysomnographically
(PSG) measured sleep followed by a 26 h constant routine. During the constant
routine, 2 h urine samples were collected and analysed for the melatonin
metabolite, 6-sulphatoxymelatonin (aMT.6S). This was used to determine total
melatonin excretion. As well, the following circadian melatonin parameters were
calculated from fifth order polynomial curve fitting analyses, the goodness of
the polynomial curve fit, peak melatonin concentration, the phase of the
melatonin rhythm, and melatonin and sleep rhythm synchrony. Apart for one
control, all subjects showed significant circadian melatonin rhythms. Although
insomniacs showed a greater amount of wakefulness, less sleep in total, and lower
sleep efficiency, no significant group differences were observed in any of the
melatonin parameters. In addition, while subjects with more reliable melatonin
curve fits showed shorter sleep latencies and higher sleep efficiencies,
correlational analyses revealed no other significant relationships between any
melatonin and PSG sleep parameters. Overall, the present results suggest that
neither melatonin amplitude nor phase are related to sleep quality in the aged.
PMID- 10188136
TI - Prediction of sleep-disordered breathing by unattended overnight oximetry.
AB - Between January 1994 and July 1997, 793 patients suspected of having sleep
disordered breathing had unattended overnight oximetry in their homes followed by
laboratory polysomnography. From the oximetry data we extracted cumulative
percentage time at SaO2 < 90% (CT90) and a saturation variability index (delta
Index, the sum of the differences between successive readings divided by the
number of readings - 1). CT90 was weakly correlated with polysomnographic
apnea/hypopnea index (AHI). (Spearman rho = 0.36, P < 0.0001) and with delta
Index (rho = 0.71, P < 0.0001). delta Index was more closely correlated with AHI
(rho = 0.59, P < 0.0001). In a multivariate model, only delta Index was
significantly related to AHI, the relationship being AHI = 18.8 delta Index +
7.7. The 95% CI for the coefficient were 16.2, 21.4, and for the constant were
5.8, 9.7. The sensitivity of a delta Index cut-off of 0.4 for the detection of
AHI > or = 15 was 88%, for detection of AHI > or = 20 was 90% and for the
detection of AHI > or = 25 was 91%. The specificity of delta Index > or = 0.4 for
AHI > or = 15 was 40%. In 113 further patients, oximetry was performed
simultaneously with laboratory polysomnography. Under these circumstances delta
Index was more closely correlated with AHI (rho = 0.74, P < 0.0001), as was CT90
(rho = 0.58, P < 0.0001). Sensitivity of delta Index > or = 0.4 for detection of
AHI > or = 15 was not improved at 88%, but specificity was better at 70%. We
concluded that oximetry using a saturation variability index is sensitive but
nonspecific for the detection of obstructive sleep apnea, and that few false
negative but a significant proportion of false positive results arise from night
to-night variability.
PMID- 10188138
TI - Sleep-disordered breathing in a predominantly African-American pediatric
population.
AB - The goal of this study was to characterize sleep and respiratory parameters in
children with sleep-disordered breathing (SDB) as compared to children without
SDB. Data are from 198 children and adolescents referred for sleep center
evaluation, 128 of whom were diagnosed with SDB. In children with SDB, obesity (>
95% wgt for age) was more common than being severely underweight (< 5% wgt for
age), but only the older children with SDB were heavier than age-matched normal
sleepers. Children with SDB had increased EEG arousals; sleep architecture was
not otherwise significantly different from the non-SDB group. African-American
children with SDB had significantly greater oxygen desaturation with obstructive
events compared to Caucasian and Latino children. It appears that the role of
obesity as a risk factor for obstructive sleep apnea (OSA) increases in children
above the age of 8-years. Additionally, African-American children with SDB may be
at increased risk for hypoxemia and cardiovascular consequences of SDB.
PMID- 10188139
TI - Cognitive function and treatment of obstructive sleep apnea syndrome.
AB - Among patients with obstructive sleep apnea syndrome (OSAS), impairment of
cognitive function, i.e. deficits in memory, attention, and visuconstructive
abilities are common. We applied different forms of treatment for patients with
newly diagnosed OSAS in a randomized study with a one-year follow-up. Patients
with BMI > 40 kg/m2 were excluded. After the initial diagnostic work-up, male
patients were considered to be candidates for either nasal continuous airway
pressure (nCPAP) (27 patients) or surgical treatment (uvulopalatopharyngoplasty
with or without mandibular osteotomy) (23 patients). Within the groups, the
patients were then randomized to active treatment (nCPAP/surgery) or to
conservative management. Cognitive function and severity of OSAS were assessed
prior to treatment and 3 and 12 months later. At 12 months, all patients on nCPAP
had a normal ODI4 index (< 10), and were significantly less somnolent than their
controls; 3/11 of the surgically treated patients had a normal ODI4 index.
Daytime somnolence was significantly less severe in the surgically treated
patients than in their controls. Cognitive function did not correlate importantly
with daytime sleepiness or severity of OSAS; the best Pearson pairwise
correlation coefficient was between ODI4 and the Bourdon-Wiersma (r = 0.36).
Success in treatment of OSAS did not affect neuropsychological outcome. We
concluded that the standard cognitive test battery is insufficiently sensitive to
identify positive changes in patients with OSAS, especially among those with a
high level of overall mental functioning.
PMID- 10188140
TI - A 50-Hz electromagnetic field impairs sleep.
AB - In view of reports of health problems induced by low frequency (50-60 Hz)
electromagnetic fields (EMF), we carried out a study in 18 healthy subjects,
comparing sleep with and without exposure to a 50 Hz/1 mu Tesla electrical field.
We found that the EMF condition was associated with reduced: total sleep time
(TST), sleep efficiency, stages 3 + 4 slow wave sleep (SWS), and slow wave
activity (SWA). Circulating melatonin, growth hormone, prolactin, testosterone or
cortisol were not affected. The results suggest that commonly occurring low
frequency electromagnetic fields may interfere with sleep.
PMID- 10188141
TI - Concentration of an epidermal growth factor in blood serum of males during
topical treatment of psoriasis.
AB - Epidermal growth factor (EGF) is a mitogen that stimulates cell division of
various cells of epidermal origin. The present study was undertaken to clarify
whether the serum level of EGF is correlated with the disease activity during
local therapy with dithranol in psoriasis. We examined serum EGF concentrations
in acute and chronic psoriasis before and after topical treatment with dithranol
and the correlation with Psoriasis Activity and Severity Index (PASI). Male
patients were divided into two groups: acute psoriasis (AP, 18 cases) and chronic
psoriasis (CP, 17 cases). A control group C consisted of 20 healthy male
volunteers. Radioimmunoassay of EGF was performed using the reagent pack
(Amersham, UK). In the CP group mean EGF was higher before treatment than in the
AP and C groups, but not significantly. EGF concentration after local treatment
was higher in the CP group than the AP group (P < 0.02); the AP group, however,
showed statistically significant decrease of EGF after the treatment (P < 0.04).
No correlation between EGF and PASI was found. Serum EGF concentration increased
in 19/35 treated patients.
PMID- 10188142
TI - Characterization of [3H]substance P binding sites in human skin.
AB - Radioligand binding experiments were performed with crude homogenates from normal
human skin in order to investigate substance P receptor density. Binding of
[3H]substance P ([3H]SP) reached equilibrium after 20 min and was saturable
analysis of saturation curves gave a significantly better fit using two-site
binding compared to the single-site model. Competition studies employing some
selective agonists for NK1, NK2 and NK3 receptors have demonstrated that only the
NK1 selective agonist, [Sar9, Met(O2)11]-SP, was a competitor for [3H]SP binding.
In addition, the non-hydrolyzable guanosine 5'-0-(3-thiotriphosphate) altered the
dissociation of SP from NK1 receptors by increasing the number of low-affinity
sites. These data show that in the skin [3H]SP binds to a single population of
substance P high-affinity sites, which represent NK1-type receptors.
PMID- 10188143
TI - Increased serum IL-6, TNF-alpha and IL-10 levels in patients with bullous
pemphigoid: relationships with disease activity.
AB - AIM: The present report analyzes the serum levels of three cytokines, interleukin
6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) in
15 patients with bullous pemphigoid (BP) (compared with 20 healthy controls) to
evaluate a possible involvement of these biological modulators in the clinical
expression of this disease. BACKGROUND: BP is a rare bullous disease of
autoimmune origin with evidence of inflammatory processes that cause skin lesions
with local increase of various pro-inflammatory mediators. METHODS: Determination
of cytokine concentrations were obtained employing commercially available ELISA
kits. RESULTS: The sera of BP patients showed increased levels of these three
cytokines (P < 0.01). When the number of skin lesions (blisters and/or erosion)
of each patient, employed as a marker of disease activity, was correlated with
the serum levels of IL-6 and TNF-alpha, significant correlations were found (IL
6: P < 0.01 and TNF-alpha: P < 0.01, respectively), suggesting a possible role of
these mediators in the development of BP blisters. The serum levels of IL-6 also
correlated (P = 0.01 with those of serum C reactive protein (CRP), an acute-phase
protein induced by IL-6 in hepatocytes. In addition, serum TNF-alpha and sE
selectin (an adhesion molecule previously reported to be increased by this
cytokine) levels were also correlated (P < 0.05). CONCLUSIONS: On the basis of
these data, it may be indicated that at least IL-6 and TNF-alpha are associated
with the clinical expression of BP and that the endothelial activation (possibly
induced by the TNF-alpha activity), seems to be an important phase of this
dermatosis.
PMID- 10188144
TI - Efficacy and safety of mizolastine 10 mg in a placebo-controlled comparison with
loratadine in chronic idiopathic urticaria: results of the MILOR Study.
AB - BACKGROUND: Mizolastine is a novel histamine H1-antagonist registered in Europe
for the management of allergic rhinitis and urticaria. OBJECTIVES: To compare the
clinical efficacy and safety of mizolastine with loratadine and placebo in
patients with chronic idiopathic urticaria (CIU). METHODS: A multicentre, double
blind, parallel group study was designed in which 247 patients with CIU were
randomised after a 1-week placebo run-in period to 10 mg daily mizolastine (n =
88), 10 mg daily loratadine (n = 79), or placebo (n = 80) for a 4-week treatment
period. RESULTS: Mizolastine and loratadine both relieved symptoms of CIU. After
2 weeks' treatment, the severity of pruritus (visual analogue score (VAS)
assessed by patients) decreased significantly in both the mizolastine and
loratadine groups compared with placebo (mizolastine: -36.7 mm, P = 0.0001;
loratadine: -29.8, P = 0.0071; placebo: -16.3); this improvement with both active
treatments was maintained throughout the treatment period, the difference being
significant only for the mizolastine group (P = 0.0090). Both active treatments
were also associated with reduced weekly episodes of urticaria compared with
placebo, which was significant after 2 weeks' treatment (mizolastine: 7.9
episodes, P = 0.0061; loratadine: 8.3, P = 0.0221; placebo: 13.3). Angioedema was
improved to a clinically significant extent with mizolastine, and loratadine
compared with placebo in those patients who had this symptom before treatment.
Overall tolerability of both treatments was similar to placebo, and there were no
clinically relevant effects on cardiac repolarisation with either mizolastine or
loratadine. CONCLUSION: Mizolastine (10 mg daily) is confirmed as an effective
and well tolerated agent, comparable to loratadine and superior to placebo, for
the management of CIU. Mizolastine acted as rapidly as loratadine in improving
urticarial symptoms from the first day of treatment.
PMID- 10188145
TI - Altered sperm function or sperm antibodies are not associated with chlamydial
antibodies in infertile men with leucocytospermia.
AB - OBJECTIVE: Leucocytospermia, defined as a concentration of more than 10(6)
leucocytes/ml of seminal fluid in patients without clinical symptoms due to an
adnexitis, is seen in about 10% of patients in an infertility department.
Infection with Chlamydia trachomatis is possibly relevant as other pathogenic
bacteria were not cultured from the semen in significant numbers. SETTING:
University Clinic, Department of Andrology. PATIENTS: Two hundred and seven
patients attending the department for male infertility investigation. METHODS:
Analysis on each semen sample included determination of leucocyte count and the
MAR test for the detection of sperm antibodies. Chlamydial antibodies in semen
were determined using an on-slide enzyme immunoassay. RESULTS: No differences
between leucocyte counts in patients with and without chlamydial antibodies were
detected. In addition, no differences in the sperm parameters or results of MAR
tests in these two groups was seen. There were no correlations between the
leucocyte count and sperm parameters, including the MAR-test results.
CONCLUSIONS: We conclude that antibodies to chlamydiae in semen are not
associated with leucocytospermia. Leucocytospermia per se does not appear to be
significant for the sperm functions and immune responses to sperm.
PMID- 10188146
TI - Umbilical endometriosis.
AB - Cutaneous endometriosis is a well known but rare phenomenon. We present a case of
spontaneous umbilical endometriosis. The patient revealed a polypoid, brown-blue
nodule within the umbilical depression with the typical history of monthly
bleeding from the umbilicus. The differential diagnoses are summarized.
PMID- 10188147
TI - Keratosis palmoplantaris varians of Wachters.
AB - We report a case of hereditary palmoplantar keratosis (HPPK) causing a
progressive reduction of the prehension capacity of the fingers due to the
presence of hyperkeratotic lesions which had appeared approximately 25 years
earlier. These lesions, also involving the soles, appeared yellowish in color,
linear or round in shape, symmetrical and often confluent, developed prevalently
at the pressure points displaying a non-transgrediens pattern. The histological
examination, clinical picture and careful analysis of the literature enabled us
to define this form as 'keratosis palmoplantaris varians of Wachters'. As a
contribution to a conclusive HPPK classification we discuss the differential
diagnosis of this disorder most commonly identified through nummular-linear
keratoses also known as Siemens' syndrome.
PMID- 10188148
TI - Two cases of tinea pedis caused by Scytalidium hyalinum.
AB - Two cases of tinea pedis due to Scytalidium hyalinum, the first to be described
in Italy, are reported. The patients were a 41-year-old woman and a 35-year-old
man who had spent periods in the Caribbean. The clinical manifestations were
indistinguishable from those caused by dermatophytes. In the women they were
striking with 'moccasin foot' type lesions, whereas in the man they were less
evident, with minor plantar desquamation and interdigital maceration. Diagnosis
was based on direct mycological microscopic examination and culture. Clinical and
mycological remission were obtained with systemic itraconazole therapy. These
cases are reported because infections caused by Scytalidium hyalinum are rare in
Europe and their clinical and mycological diagnosis, as well as therapy, may be
problematic.
PMID- 10188149
TI - Stress-induced SAPHO syndrome.
AB - We describe the case of a woman with the classic combination of features of
synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome, including
pustulosis palmo-plantaris and anterior chest wall involvement. The varying
symptomology, etiology and pathogenesis of this syndrome and the contribution of
stress are discussed. The authors ascribe the dearth of reported cases to lack of
awareness and recognition of SAPHO, and not to the real incidence of the
syndrome.
PMID- 10188150
TI - Familial primary cryofibrinogenemia.
AB - BACKGROUND: To our best knowledge this is the second case ever described of
familial primary cryofibrinogenemia (CFG). PATIENTS: A 29-year-old Moroccan
female and two of her three children suffered from painful purpura, slow healing
small ulcerations and edema of both feet during the winter season. Laboratory
investigations revealed the presence of cryofibrinogen in their blood plasma. All
three patients were otherwise healthy and no associated disease could be
demonstrated. CONCLUSIONS: The diagnosis of CFG has to be considered in patients
with livedo reticularis, edema, painful purpura and slow healing ulcera after
cold exposure. Cryofibrinogen-precipitates in the blood plasma have to be
determined. Because secondary CFG occurs much more frequently than the primary
form, it is important to rule out associated diseases through extensive physical
examination and laboratory investigations. This communication also stresses the
importance of a through family history of patients with CFG. An autosomal
dominant mode of inheritance is supposed.
PMID- 10188151
TI - Systemic sarcoidosis presenting with multiple tattoo granulomas and an extra
tattoo cutaneous granuloma.
AB - We describe a 29 year old Caucasian man who developed cutaneous sarcoidosis
manifesting itself as a tumour at the left outer canthus clinically mimicking a
basal cell carcinoma and nine tattoo granulomas. Subsequent investigation
revealed that the patient was also suffering from systemic sarcoidosis.
PMID- 10188152
TI - Congenital poikiloderma with unusual hypopigmentation and acral blistering at
birth.
AB - Congenital poikiloderma is an uncommon hereditary disorder. It has been reported
in association with various syndrome. No case has previously been reported from
this environment. We report a case of congenital poikiloderma in a two and a half
year old female Nigerian associated with unusual generalised hypopigmentation and
acral blisters at birth. The child subsequently developed macular
hyperpigmentation on an erythematous background and atrophy of the skin. Although
she had some features which were suggestive of Rothmund-Thomson syndrome (RTS),
the presence of hypopigmentation at birth, along with acral blistering, was noted
to be peculiar to this child. We, therefore, feel that this case presents a
distinct variant of congenital poikiloderma that has not been described
previously.
PMID- 10188153
TI - Penile pyoderma gangrenosum.
AB - Pyoderma gangrenosum is a rare ulcerating inflammatory skin disease. Genital
involvement has been rarely reported. We report a 24-year-old man with penile
pyoderma gangrenosum who was treated with systemic corticosteroids.
PMID- 10188154
TI - Incidence peaks in melanoma and biopsy confirmed benign skin lesions--an effect
of media campaigns?
PMID- 10188155
TI - Distant cutaneous manifestation of Crohn's disease presenting as a granulomatous
erysipelas-like lesion.
PMID- 10188156
TI - The use of amikacin in the treatment of primary cutaneous mycobacteriosis due to
Mycobacterium fortuitum.
PMID- 10188157
TI - Short-term oral cyclosporine for chronic idiopathic urticaria.
PMID- 10188158
TI - Allergic contact dermatitis due to pine wood.
PMID- 10188159
TI - Primary cutaneous B-cell lymphoma: treatment with low dose intralesional
recombinant interferon-alpha 2A.
PMID- 10188160
TI - Sporadic reticulate acropigmentation of Kitamura on pale skin.
PMID- 10188161
TI - Teaching dermatosurgery.
PMID- 10188162
TI - Multiple linear syringocystadenoma papilliferum.
PMID- 10188163
TI - A case of Sjogren-Larsson syndrome.
PMID- 10188165
TI - The utility of histologic examination in benign skin lesions.
PMID- 10188164
TI - Ulcerative sarcoidosis.
PMID- 10188166
TI - Cutaneous symptoms of Gardner's syndrome.
PMID- 10188167
TI - Fish tank granuloma: response to treatment with clarithromycin.
PMID- 10188168
TI - Herpetiform pemphigus.
PMID- 10188169
TI - International symposium on urticaria (allergic? autoimmune? inflammatory?) Bari,
Italy, 29-30 May, 1998.
PMID- 10188170
TI - [A review of the types of parasite-host relations in ixodid ticks].
AB - In the first type of mutual relationships the ixodid ticks expose an evident
pathogenicity to vertebrate hosts (tick toxicoses) and in the second type the
hosts expose a resistance on a base of organism immune system activisation in a
response to blood sucking. In the third type of relationships an interaction
between the ticks and hosts have a dynamic character (tolerability of host). The
first type of relationships leading to a selective elimination of hosts according
to our opinion means a comparatively youth of relationships. The third type
represent ancient and long term relationships. The second type probably having
been widely spread in a historical past occupies an intermediate position.
Depending upon areal the ticks of the same type expose different degree of the
pathogenicity. Even an acquired resistance of the host does exist in natural
conditions, it is a transient phenomenon.
PMID- 10188171
TI - [Transovarial and transphasic transmissions of Borrelia by the taiga tick Ixodes
persulcatus (Ixodidae)].
AB - Three generations of the taiga tick Ixodes persulcatus, the descendants from
naturally infected females, have been examined by means of dark field and phase
contrast microscopies and indirect immunofluorescent reactions with monoclonal
antibodies. Location of borreliae in oocytes was examined by means of electron
microscopy. The examined ticks derived from 9 females collected in the Novgorod
Province, from 6 females of 1st laboratory generation and 5 females of the 2nd
generation. In total, 250 larvae, 178 nymphs, 59 females and 70 males of three
consequent generation have been examined. Almost 100% of descendants of naturally
infected females were infected with Borrelia burgdorferi s. l. and similar
infection rate was observed in unfed tick larvae collected in field conditions.
The borreliae received transovarially to larvae of the 1st generation then were
transmitted to 100% nymphs and imago of this generation and two next generations.
PMID- 10188172
TI - [The relationship of the susceptibility of mosquitoes to the causative agents of
malaria to their taxonomic position and the geographical origin of the
interacting organisms].
AB - The belonging of mosquitos to certain taxonomic group does not show a
susceptibility to certain group of malaria parasites, but point out that this
susceptibility should not be excluded off studies without preliminary checking.
There is no correlation between taxonomic relations of mosquito species and their
susceptibility to malaria parasites. Geographical isolation of microorganisms and
insects does not guarantee an absence of susceptibility. A susceptibility is
possible even in those cases, when a long coevolutionary process between
organisms do not take place. Generally the susceptibility of mosquitos to exotic
species or strains of Plasmodium is lower. Plasmodia are capable to adapt quickly
to new vectors.
PMID- 10188173
TI - [The ultrastructure of Blastocystis galli from chickens].
AB - The ultrastructure stages of Blastocystis galli were studied in chicken's
intestine and in laboratory cultures. There were found morphological structures:
surface coat (cell from chickens' intestine showed a very thick surface coat);
cell membrane--there were some small electron-opaque deepening "pockets" on the
membrane; inner membrane; endoplasmic reticulum with attached ribosomes, which
present in the cytoplasm; all cells contained numerous of small vacuoles and
large glycogen inclusions in cytoplasm; mitochondria with tubular cristae;
nucleus with granules condensed chromatin; central vacuole; Golgi complex was
represented by number of plates grouped in a pite; the cyst-like forms were
surrounded by multilayered wall.
PMID- 10188174
TI - New horizons in health.
PMID- 10188175
TI - Health Promotion and Education.
PMID- 10188176
TI - New horizons in health--from vision to practice.
PMID- 10188177
TI - The power of partnership in health promotion.
PMID- 10188178
TI - Health as a fundamental right for all children.
PMID- 10188179
TI - Bridging from Jakarta.
PMID- 10188180
TI - [HYPP: hyperkalemic periodic paralysis in the horse].
AB - Hyperkalaemic periodic paralysis(HYPP) is characterized by intermittent episodes
of muscular tremor, weakness, and collapse, and is probably caused by abnormal
electrolyte transport in the muscle cell membrane. During an episode of HYPP,
most animals are severely hyperkalaemic. HYPP is a hereditary disease and occurs
only in American Quarter horses or crossbreds. Because these horses are now being
imported into the Netherlands, HYPP should be included in the differential
diagnosis of horses showing signs of muscle tremor, paresis, or paralysis. The
present article reviews the literature on HYPP and describes a case showing
typical signs of the disease.
PMID- 10188182
TI - [The veterinary disciplinary board].
PMID- 10188181
TI - [Epidemiologic aspects of scrapie and BSE including an analysis of risk factors].
AB - After a discussion of the different hypotheses about the causative agent of prion
diseases, various aspects of the two most important animal prion diseases, i.e.
BSE and scrapie are described. This thesis focuses on the search for a
preclinical diagnosis. A major breakthrough was the discovery of a new technique
for detecting the disease-associated protein in tonsillar biopsies from scrapie
infected sheep long before clinical signs appeared. Another essential part of the
studies described in this thesis concerned a risk analysis for BSE in a country
like the Netherlands. Major risk factors were assessed, including an assessment
of the efficacy of Dutch rendering procedures in the inactivation of the agents
of scrapie and BSE.
PMID- 10188183
TI - [The practice, the law, the electronic early advice and delivery system and the
branch code table].
PMID- 10188184
TI - [Part-time-timeshare].
PMID- 10188185
TI - [Risks in treating sport horses].
PMID- 10188186
TI - [Satellite project for animal health fits together very well in pro-active
thinking. Theoretical trial for cattlemen and veterinarians].
PMID- 10188187
TI - Induction and inhibition of pesticide-metabolizing enzymes: roles in synergism of
pesticides and pesticide action.
AB - Synergism of the toxic action of pesticides is discussed with particular emphasis
on the methylenedioxyphenyl (benzodioxole) (MDP) synergists and on how studies of
these compounds may relate to the general significance of pesticide synergism.
MDP compounds function as both inhibitors and inducers of cytochrome P450
isoforms, the two processes proceeding, in vivo, at different rates. Inhibition
is mediated through the formation of metabolite inhibitory complexes, and
induction involves both aryl hydrocarbon (Ah)-dependent and Ah-independent
mechanisms. The significance of this biphasic effect on multienzyme xenobiotic
metabolizing systems is illustrated by considerations of the insecticide phorate.
PMID- 10188188
TI - Low-dose bioactivity of xenoestrogens in animals: fetal exposure to low doses of
methoxychlor and other xenoestrogens increases adult prostate size in mice.
AB - The hormonal activity of natural estrogens is influenced by the degree to which
they bind to serum proteins. In the pregnant female and in the fetus, greater
than 99% of estradiol may be bound by serum binding proteins. Therefore, even
though total serum levels of estradiol appear very high in fetuses, we have found
that in rodent fetuses, there is a very low free concentration of estradiol (0.2
pg/ml). Naturally occurring variation in fetal serum estradiol predicts
differences in numerous postnatal traits, including prostate size. In addition,
when this low level of free estradiol was experimentally increased from 0.2 to
0.3 pg/ml during the last third of fetal life, treated male mice showed an
increase in adult prostate weight. Fetal exposure to low doses of xenobiotic
estrogens by feeding to pregnant females, including the compounds methoxychlor
(20 and 2000 micrograms/kg body weight), DES (0.02 to 2 micrograms/kg body
weight) and bisphenol A (2 and 20 micrograms/kg body weight), also led to
increased prostate weight in adulthood. In contrast, fetal doses of natural
estradiol and DES above the physiological range of estrogenic activity, and
within a toxicological dose range, led to the opposite outcome, a reduction in
subsequent adult prostate weight. This indicates that it may be impossible to
assess endocrine-disrupting activities in response to low doses within a
physiological range of activity by using high, toxic doses of xenoestrogens in
testing procedures. We have developed approaches in vitro to predict the
potential estrogenic bioactivity of compounds in the physiologically relevant
range in animals and humans. We address the following factors in predicting the
final observed endocrine-disrupting effect in the animal: (1) the intrinsic
estrogenic activity of a given molecule, (2) the effective free concentration
determined by how the molecule is carried in serum, (3) partitioning between
aqueous and lipid compartments in body and cell lipids, and (4) absorption and
metabolism relative to the route of exposure. The studies and strategies we
describe are important in developing criteria for a tiered testing system for the
detection of estrogenic chemicals as well as endocrine-disrupting chemicals with
different modes of action.
PMID- 10188189
TI - Neuroendocrine and reproductive effects of contemporary-use pesticides.
AB - Work in our laboratory has focused on the hypothesis that certain environmental
contaminants will interfere with reproductive function because they disrupt the
neuroendocrine regulation of gonadal function. In this article, we review the
evidence that certain classes of contemporary-use pesticides alter gonadotropin
secretion through a disruption of hypothalamic mechanisms. Specifically, we
discuss the effect of formamidine and dithiocarbamate pesticides on the
noradrenergic control of pituitary hormone secretion, ovarian function, and
pregnancy in the rat. This is followed by a review of studies evaluating the
effect of a chlorotriazine herbicide, atrazine, on the hormonal control of
ovulation and lactation. We also discuss the physiological consequences of these
endocrine alterations in the female, how toxicant-induced endocrine alterations
may differ in physiological outcome in the male and female, and the fact that the
reproductive risk assessment of some pesticides that act on the central nervous
system (CNS) may be influenced by the development of tolerance.
PMID- 10188190
TI - The estrogenic and antiandrogenic pesticide methoxychlor alters the reproductive
tract and behavior without affecting pituitary size or LH and prolactin secretion
in male rats.
AB - This study was designed to determine if long-term exposure to high doses of
methoxychlor (M) would alter pituitary or testicular endocrine functions in
either an estrogenic or antiandrogenic manner. Weanling male Long-Evans hooded
rats were dosed daily with M (po) at 0, 200, 300, or 400 mg kg-1 day-1 for 10
months. Methoxychlor treatment delayed puberty by as much as 10 weeks and reduced
fertility and copulatory plug formation in a dose-related manner at the initial
mating. During mating, M-treated males exhibited shorter latencies to mount and
ejaculate versus control males, but the number of intromissions prior to
ejaculation was unaffected, indicating that M enhanced the arousal level in the
males in an estrogen-dependent manner. Most treated males eventually mated but
time-to-pregnancy was lengthened. Very low sperm counts were associated with
infertility, while prolonged delays in puberty reduced fecundity. Methoxychlor
treatment with 200 to 400 mg kg-1 day-1 failed to mimic the chronic effects of a
sustained (8 months) low dose of estradiol-17 beta (3-mm silastic implants) on
pituitary or testicular hormone levels. Estradiol administration increased
pituitary weight 4-fold, serum levels of luteinizing hormone (LH) were reduced by
almost 50%, and serum prolactin was increased 40-fold, while M did not affect any
of these measures. These data demonstrate that M affects the CNS, epididymal
sperm numbers, and the accessory sex glands and delays mating without
significantly affecting the secretion of LH, prolactin, or testosterone. These
data indicate that M did not alter pituitary endocrine function in either an
estrogenic or antiandrogenic manner. To our knowledge, these data provide the
first in vivo example of such a pronounced degree of target tissue selectivity to
an environmental endocrine-disrupting chemical.
PMID- 10188191
TI - Environmental antiandrogens: low doses of the fungicide vinclozolin alter sexual
differentiation of the male rat.
AB - In humans and rodents, exposure to antiandrogenic chemicals during sexual
differentiation can produce malformations of the reproductive tract. Perinatal
administration of 100 or 200 mg vinclozolin (V) kg-1 day-1 during sexual
differentiation in rats induces female-like anogenital distance (AGD), retained
nipples, cleft phallus with hypospadias, suprainguinal ectopic scrota/testes, a
vaginal pouch, epididymal granulomas, and small to absent sex accessory glands in
male offspring. Vinclozolin is metabolized to at least two active forms, M1 and
M2, that display antiandrogenic activity by binding the androgen receptor (AR).
Here, we present information on the reproductive effects of oral treatment with
low dosage levels of V during sexual differentiation of the male rat. Vinclozolin
was administered to the dam at 0, 3.125, 6.25, 12.5, 25, 50, or 100 mg kg-1 day-1
from gestational day 14 to postnatal day 3 (the period of fetal/neonatal
testicular testosterone synthesis and sexual differentiation). At doses of 3.125
mg V kg-1 and above, AGD was significantly reduced in newborn male offspring and
the incidence of areolas was increased. These effects were associated with
permanent alterations in other androgen-dependent tissues. Ventral prostate
weight in one year old male offspring was reduced in all treatment groups
(significant at 6.25, 25, 50, and 100 mg kg-1 day-1), and permanent nipples were
detected in males at 3.125 (1.4%), 6.25 (3.6%), 12.5 (3.9%), 25 (8.5%), 50 (91%),
and 100 (100%) mg V kg-1 day-1. To date, permanent nipples have not been observed
in a control male from any study in our laboratory. Vinclozolin treatment at 50
and 100 mg kg-1 day-1 induced reproductive tract malformations and reduced
ejaculated sperm numbers and fertility. Even though all of the effects of V
likely result from the same initial event (AR binding), the different endpoints
displayed a wide variety of dose-response curves and ED50's. The dose-response
data for several of the functional endpoints failed to display an obvious
threshold. These data demonstrate that V produces subtle alterations in sexual
differentiation of the external genitalia, ventral prostate, and nipple tissue in
male rat offspring at dosage levels below the previously described no-observed
effect-level (NOEL). These effects occur at a dosage level an order of magnitude
below that required to induce malformations and reduce fertility. Hence,
multigenerational reproduction studies of antiandrogenic chemicals that were not
conducted under the Environmental Protection Agency's new Harmonized
Multigenerational Test Guidelines, which include endpoints sensitive to
antiandrogens at low dosage levels, could yield a NOEL that is at least an order
of magnitude too high.
PMID- 10188192
TI - Peripubertal exposure to the antiandrogenic fungicide, vinclozolin, delays
puberty, inhibits the development of androgen-dependent tissues, and alters
androgen receptor function in the male rat.
AB - Vinclozolin is a well-characterized antiandrogenic fungicide. It produces adverse
effects when administered during sexual differentiation, and it alters
reproductive function in adult male rats by acting as an androgen-antagonist. Two
active metabolites of vinclozolin, M1 and M2, compete with natural androgens for
the rat and human androgen receptors (ARs), an effect that blocks androgen
induced gene expression in vivo and in vitro. In addition to their effects during
perinatal life, androgens play a key role in pubertal maturation in young males.
In this regard, the present study was designed to examine the effects of
peripubertal oral administration of vinclozolin (0, 10, 30, or 100 mg kg-1 day-1)
on morphological landmarks of puberty, hormone levels, and sex accessory gland
development in male rats. In addition, as binding of the M1 and M2 to AR alter
the subcellular distribution of AR by inhibiting AR-DNA binding, we examined the
effects of vinclozolin on AR distribution in the target cells after in vivo
treatment. We also examined serum levels of vinclozolin, M1, and M2 in the
treated males so that these could be related to the effects on the reproductive
tract and AR distribution. Vinclozolin treatment delayed pubertal maturation (at
30 and 100 mg kg-1 day-1) and retarded sex accessory gland and epididymal growth.
Serum luteinizing hormone (LH; significant at all dosage levels) and testosterone
and 5 alpha-androstane, 3 alpha, 17 beta-diol (at 100 mg kg-1 day-1) levels were
increased. Testis size and sperm production, however, were unaffected. It was
apparent that these effects were concurrent with subtle alterations in the
subcellular distribution of AR. In control animals, most AR were in the high salt
cell fraction, apparently bound to the natural ligand and DNA. Vinclozolin
treatment reduced the amount of AR in the high salt (bound to DNA) fraction and
it increased AR levels in the low salt (inactive, not bound to DNA) fraction. M1
and M2 were found in the serum of animals from the two highest dosage groups, but
they were present at levels well below their K1 values. In summary, these results
suggest that when the vinclozolin metabolites occupy a small percentage of AR in
the cell, this prevents maximal AR-DNA binding and alters in vivo androgen
dependent gene expression and protein synthesis, which in turn results in obvious
alterations of morphological development and serum hormone levels. It is
noteworthy that similar exposures during prenatal life result in a high incidence
of malformations in male rats.
PMID- 10188193
TI - The fungicide procymidone alters sexual differentiation in the male rat by acting
as an androgen-receptor antagonist in vivo and in vitro.
AB - Procymidone is a dicarboximide fungicide structurally related to the well
characterized fungicide vinclozolin. Vinclozolin metabolites bind to mammalian
androgen receptors (AR) and act as AR antagonists, inhibiting androgen-dependent
gene expression in vivo and in vitro by inhibiting AR-binding to DNA. The current
study was designed to determine if procymidone acted as an AR antagonist in vitro
and to describe the dosage levels of procymidone that alter sexual
differentiation in vivo. In vitro, procymidone inhibited androgen from binding
the human AR (hAR) in COS (monkey kidney) cells transfected with hAR at 3.16
microM. In vitro, procymidone acted as an androgen antagonist, inhibiting
dihydrotestosterone (DHT)-induced transcriptional activation at 0.2 microM in CV
1 cells (cotransfected with the hAR and a MMTV-luciferase reporter gene). In
vivo, maternal procymidone exposure at 0, 25, 50, 100, or 200 mg kg-1 day-1
during gestation and early lactation (gestational day 14 to postnatal day 3)
altered reproductive development of male offspring at all dosage levels tested.
Male offspring exhibited shortened anogenital distance (at 25 mg kg-1 day-1 and
above), permanent nipples, reduced weight of several androgen-dependent tissues
(levator ani and bulbocavernosus muscles, prostate, seminal vesicles, Cowper's
gland and glans penis), and malformations (hypospadias, cleft phallus, exposed os
penis, vaginal pouch, hydronephrosis, occasional hydroureter, epididymal
granulomas, and ectopic, undescended testes). In addition, perinatal procymidone
treatment had a marked effect on the histology of the lateral and ventral
prostatic and seminal vesicular tissues of the offspring (at 50 mg kg-1 day-1 and
above). These effects consisted of fibrosis, cellular infiltration, and
epithelial hyperplasia. This constellation of effects is similar to that produced
by perinatal exposure to vinclozolin. However, procymidone appears to be slightly
less potent in inducing malformations than vinclozolin by a factor of about two.
In summary, the antiandrogenic activity of procymidone was demonstrated in vivo
and in vitro in cell lines transfected with hAR. Since the role of androgens in
mammalian sexual differentiation is highly conserved, it is likely that humans
would be adversely affected by procymidone in a predictable manner if the human
fetus was exposed to sufficient levels during critical stages of intrauterine and
neonatal life.
PMID- 10188194
TI - Administration of potentially antiandrogenic pesticides (procymidone, linuron,
iprodione, chlozolinate, p,p'-DDE, and ketoconazole) and toxic substances
(dibutyl- and diethylhexyl phthalate, PCB 169, and ethane dimethane sulphonate)
during sexual differentiation produces diverse profiles of reproductive
malformations in the male rat.
AB - Antiandrogenic chemicals alter sexual differentiation by a variety of mechanisms,
and as a consequence, they induce different profiles of effects. For example, in
utero treatment with the androgen receptor (AR) antagonist, flutamide, produces
ventral prostate agenesis and testicular nondescent, while in contrast,
finasteride, an inhibitor of 5 alpha-dihydrotestosterone (DHT) synthesis, rarely,
if ever, induces such malformations. In this regard, it was recently proposed
that dibutyl phthalate (DBP) alters reproductive development by a different
mechanism of action than flutamide or vinclozolin (V), which are AR antagonists,
because the male offsprings display an unusually high incidence of testicular and
epididymal alterations--effects rarely seen after in utero flutamide or V
treatment. In this study, we present original data describing the reproductive
effects of 10 known or suspected anti-androgens, including a Leydig cell toxicant
ethane dimethane sulphonate (EDS, 50 mg kg-1 day-1), linuron (L, 100 mg kg-1 day
1), p,p'-DDE (100 mg kg-1 day-1), ketoconazole (12-50 mg kg-1 day-1), procymidone
(P, 100 mg kg-1 day-1), chlozolinate (100 mg kg-1 day-1), iprodione (100 mg kg-1
day-1), DBP (500 mg kg-1 day-1), diethylhexyl phthalate (DEHP, 750 mg kg-1 day
1), and polychlorinated biphenyl (PCB) congener no. 169 (single dose of 1.8 mg kg
1). Our analysis indicates that the chemicals discussed here can be clustered
into three or four separate groups, based on the resulting profiles of
reproductive effects. Vinclozolin, P, and DDE, known AR ligands, produce similar
profiles of toxicity. However, p,p'-DDE is less potent in this regard. DBP and
DEHP produce a profile distinct from the above AR ligands. Male offsprings
display a higher incidence of epididymal and testicular lesions than generally
seen with flutamide, P, or V even at high dosage levels. Linuron treatment
induced a level of external effects consistent with its low affinity for AR
[reduced anogenital distance (AGD), retained nipples, and a low incidence of
hypospadias]. However, L treatment also induced an unanticipated degree of
malformed epididymides and testis atrophy. In fact, the profile of effects
induced by L was similar to that seen with DBP. These results suggest that L may
display several mechanisms of endocrine toxicity, one of which involves AR
binding. Chlozolinate and iprodione did not produce any signs of maternal or
fetal endocrine toxicity at 100 mg kg-1 day-1. EDS produced severe maternal
toxicity and a 45% reduction in size at birth, which resulted in the death of all
neonates by 5 days of age. However, EDS only reduced AGD in male pups by 15%.
Ketoconazole did not demasculinize or feminize males but rather displayed anti
hormonal activities, apparently by inhibiting ovarian hormone synthesis, which
resulted in delayed delivery and whole litter loss. In summary, the above in vivo
data suggest that the chemicals we studied alter male sexual differentiation via
different mechanisms. The anti-androgens V, P, and p,p'-DDE produce flutamide
like profiles that are distinct from those seen with DBP, DEHP, and L. The
effects of PCB 169 bear little resemblance to those of any known anti-androgen.
Only in depth in vitro studies will reveal the degree to which one can rely upon
in vivo studies, like those presented here, to predict the cellular and molecular
mechanisms of developmental toxicity.
PMID- 10188195
TI - Immunotoxicity of pesticides: a review.
AB - The intricate balance that is the hallmark of the immune system shows
vulnerability to any chemical, including pesticides, that can cause structural
and functional alterations to the system. The immunotoxic effects of xenobiotics
include: histopathologic effects in immune tissues and organs; cellular
pathology; altered maturation of immunocompetent cells; changes in B and T cell
subpopulations; and functional alterations of immunocompetent cells. Pesticides,
including fungicides, herbicides, and insecticides, are the only class of
chemicals deliberately released into the environment because of their toxicity.
Around the world, millions of people are exposed to pesticides at work and/or in
their home. This article reviews evidence, from animal and human studies, on the
effects of pesticides on the immune system.
PMID- 10188196
TI - Endocrine, immune, and behavioral effects of aldicarb (carbamate), atrazine
(triazine) and nitrate (fertilizer) mixtures at groundwater concentrations.
AB - This paper describes the results of 5 years of research on interactive effects of
mixtures of aldicarb, atrazine, and nitrate on endocrine, immune, and nervous
system function. The concentrations of chemicals used were the same order of
magnitude as current maximum contaminant levels (MCLs) for all three compounds.
Such levels occur in groundwater across the United States. Dosing was through
voluntary consumption of drinking water. We used fractional and full factorial
designs with center replicates to determine multifactor effects. We used chronic
doses in experiments that varied in duration from 22 to 103 days. We tested for
changes in thyroid hormone levels, ability to make antibodies to foreign
proteins, and aggression in wild deer mice, Peromyscus maniculatus, and white
outbred Swiss Webster mice, Mus musculus, ND4 strain. Endocrine, immune, and
behavior changes occurred due to doses of mixtures, but rarely due to single
compounds at the same concentrations. Immune assay data suggest the possibility
of seasonal effects at low doses. We present a multiple-level model to help
interpret the data in the context of human health and biological conservation
concerns. We discuss six testing deficiencies of currently registered pesticides,
and suggest areas of human health concerns if present trends in pesticide use
continue.
PMID- 10188197
TI - Inadvertent exposure to xenoestrogens in children.
AB - This article reviews previous studies and presents new data on pesticide exposure
in order to provide some indications of the extent and significance of childhood
exposure to xenoestrogens, including pesticides, epoxy resins, and
polycarbonates. After more than four decades of pesticide use, little is known
about their adverse effects on health. There is a need to address the potential
risks associated with the current contamination of water, soils, and foods in
many agricultural areas. In southeastern Spain, along the Mediterranean coast,
extensive areas alongside residential zones are devoted to intensive farming in
plastic greenhouses, with the use of large amounts of pesticides. Human tissue
samples have been investigated for pesticide residues. Samples of fat from
children living in farm areas contained a total of 14 pesticides, including
lindane, HCH, heptachlor, aldrin, dieldrin, endrin, endosulfan, o,p'-DDE, and
o,p'-DDD, among others. Of the 113 samples studied, 43 were positive for one or
more pesticides, some of which have estrogenic activity. The number of new
substances that mimic the action of endogenous estrogens is increasing rapidly.
These endocrine-disrupting chemicals are not restricted to pesticides. Several
different compounds used in the food industry, in plasticizers, and in dental
restorations are also estrogenic. The few studies that have investigated their
effects in humans all indicate that concerns are warranted. If there is indeed an
association between zexposure to substances with hormone-disruptive activity and
certain disorders of sexual maturation, the incidence of such disorders should be
greater in areas where exposure to agents with this activity is high. We used a
spatial ecological design to search for variations in orchidopexy rates and to
analyze relationships between these differences and geographical variations in
exposure to pesticides. Our results are compatible with a hypothetical
association between exposure to hormone-disruptive chemicals and the induction of
cryptorchidism. Several methodological limitations in the study design make it
necessary to evaluate the results with caution. In conclusion, a closer scrutiny
is required to determine whether epoxy resins and polycarbonates contribute,
together with estrogenic pesticides, to the exposure of human consumers,
especially children, to xenoestrogens.
PMID- 10188198
TI - Herbicides and adjuvants: an evolving view.
AB - The present report examines the in vitro genotoxicity (micronucleus assay) of
herbicides and adjuvants and reports on an in vivo human study on potential
endocrine effects of pesticides, including herbicides. Adjuvants are used in
conjunction with 2,4-dichlorophenoxy acetic acid (2,4-D) and other herbicides.
Earlier pesticide applier survey results (n = 709) show that 59% of the
applicators used adjuvants, and the majority of this group used paraffinic oils
and/or surfactant mixtures. As a beginning effort to explore the role of
adjuvants and herbicides in hormonally based reproductive effects, a prospective,
controlled study was performed to analyze blood specimens from three different
exposure groups (applicators using herbicides only; applicators using both
herbicides and insecticides; and applicators using fumigants in addition to
herbicides and insecticides; and a control group composed of other agricultural
workers including organic farmers). The applicators and controls were age- and
smoking-matched. Study subjects (n = 78) were tested before, during, and after
completion of pesticide application season for the effects of pesticide products
on hormone levels in the bloodstream. Of the applicator exposure groups examined,
only the herbicide group showed significant endocrinologic differences from
controls. Free testosterone levels were significantly elevated in post-season
measurements (p = 0.032), and follicle-stimulating hormone (FSH) was
significantly decreased at the height of the season (p = 0.016) and in the post
season (p = 0.010) as compared to controls. These endocrinologic findings are
discussed in terms of their possible relationship to potential endocrine effects
of herbicides, herbicide contaminants, and adjuvants. In vitro genotoxicity
examination compared four different commercially available surfactant mixtures
with 12 different commercial herbicide products, including six different
chlorophenoxy herbicides. Only one herbicide yielded a significant dose-response
curve. All four adjuvants showed positive dose-response effects. These
preliminary data suggest that adjuvants are not inert but are toxicologically
active components added to herbicide mixtures. Whether adjuvant toxicant effects
are additive or are independent of herbicide effects is poorly understood.
PMID- 10188199
TI - Strategies for biological monitoring of exposure for contemporary-use pesticides.
AB - Pesticides are used on a massive scale in the United States. The widespread use
of these pesticides has made it virtually impossible for the average person to
avoid exposure at some level. Generally, it is believed that low-level exposure
to these pesticides does not produce acute toxic effects; however, various
cancers and other noncancer health endpoints have been associated with chronic
exposure to several groups of pesticides. Therefore, it is imperative that well
designed studies investigate the potential relationship between contemporary
pesticide exposure and health effects. For these studies to be accurate, reliable
methods for determining individual exposure must be used. Biological monitoring
is a useful tool for assessing exposure to some contemporary pesticides. As with
any analytical method, biological monitoring entails many difficulties, but, in
many instances, they can be overcome by the logical use of available information
and information acquired in carefully designed studies. At the Centers for
Disease Control and Prevention (CDC), we have acquired extensive experience in
the development and application of specific techniques for biological monitoring
of a variety of toxicants, including many of the contemporary-use pesticides. We
have used these methods to measure the internal dose of pesticides received by
people in acute and chronic incidents resulting from both environmental and
industrial exposure. Additionally, we have established normative values, or
reference ranges, of several pesticides based on measurements of their
metabolites in the urine of randomly selected adults in the US population. These
data have been successfully used to distinguish overt exposures from 'background'
exposure. In this paper, we present several examples of the usefulness of
biological monitoring in urine and blood and describe the difficulties involved
with developing methods in these matrices. We also present a general strategy,
considerations, and recommendations for developing biological monitoring
techniques for measuring the internal dose of contemporary-use pesticides.
PMID- 10188200
TI - The functional and structural observations of the neonatal reproductive system of
alligators exposed in ovo to atrazine, 2,4-D, or estradiol.
AB - Wild alligators exposed to persistent organochlorine contaminants, municipal
waste compounds, and contemporary-use herbicides exhibit reproductive alterations
that are thought to be caused by endocrine disruption. This study tests the
hypothesis that these alterations, at least in part, result from exposure of
alligator embryos to contemporary-use herbicides. Alligator eggs were collected
early in development, exposed to estradiol-17 beta, atrazine, or 2,4-D (at
dosages of 0.14, 1.4, and 14 ppm, plus a dosage of 0.014 ppm for estradiol-17
beta only) before the period of gonadal differentiation, and incubated at a
temperature that would produce either 100% males or 100% females. Analysis of
histology was performed on the gonads and reproductive tracts of hatchlings. In
females, epithelial cell height of the Mullerian duct and medullary regression of
the ovary were assessed, whereas in males, sex-cord diameter was measured. Eggs
incubated at the female-determining temperature produced all female hatchlings,
whereas the estradiol-17 beta treatments caused the production of females at the
male-determining temperature. Neither atrazine nor 2,4-D had this effect. Both
Mullerian duct epithelial cell height and medullary regression were increased in
estradiol-treated animals, but no differences were noted between herbicide
treated alligators and controls. A previous study found that male alligators
exposed to 14 ppm atrazine had elevated gonadal aromatase activity, but there was
no difference in sex-cord diameter in this or any other treatment group.
Additionally, we observed that hepatic aromatase activity was not altered by in
ovo exposure to any of the treatments. These results indicate that these
herbicides alone are not responsible for the gonadal abnormalities previously
reported for juvenile alligators from Lake Apopka and emphasize the importance of
analyzing both the function (i.e., steroidogenic enzyme activity) and the
structure (i.e., histological analysis) of the reproductive system. Structural
assessment alone may be insufficient for detecting subtle endocrine alterations.
PMID- 10188201
TI - Factors influencing estimation of pesticide-related wildlife mortality.
AB - Free-ranging wildlife is regularly exposed to pesticides and can serve as a
sentinel for human and environmental health. Therefore a comprehensive pesticide
hazard assessment must incorporate the effects of actual applications on free
ranging wildlife. Mortality is the most readily reported wildlife effect, and the
significance of these data can be realized only when placed in context with the
factors that affect the gathering of this type of information. This paper reviews
the variables that affect the collection of wildlife mortality data. Data show
that most effects on wildlife are not observed, and much of observed mortality is
not reported. Delays in reporting or in the response to a report and exposure to
multiple stressors distort the exposure-effect relationship and can result in
uncertainty in determining the cause of death. The synthesis of information
strongly indicates that the actual number of affected animals exceeds the number
recovered.
PMID- 10188202
TI - Dieldrin reduces male production and sex ratio in Daphnia galeata mendotae.
AB - We used the sex ratio of neonate Daphnia, as well as the more standard endpoints
of adult survivorship and fecundity and neonatal morphology, as an assay for
detecting the effects of the insecticides endosulfan and dieldrin. Dieldrin
caused a decrease in sex ratio (number of males/number of males plus females); we
observed no endosulfan effect. We estimated (by extrapolation) that the sex ratio
was reduced by dieldrin from concentrations of about 30 ppb and higher, based on
a linear decrease in sex ratio with log dieldrin concentrations from 50 to 600
ppb. Neither insecticide significantly affected adult survival or clutch size.
Because sex ratio changed but total neonate production did not change, the data
suggest that the effect of dieldrin was on the sex-determining system during
embryogenesis. Neither insecticide caused morphological abnormalities. Mixtures
of the two pesticides produced only additive effects.
PMID- 10188203
TI - Assessment of risk reduction strategies for the management of agricultural
nonpoint source pesticide runoff in estuarine ecosystems.
AB - Agricultural nonpoint source (NPS) runoff may result in significant discharges of
pesticides, suspended sediments, and fertilizers into estuarine habitats adjacent
to agricultural areas or downstream from agricultural watersheds. Exposure of
estuarine fin fish and shellfish to toxic levels of pesticides may occur,
resulting in significant declines in field populations. Integrated pest
management (IPM), best management practices (BMP), and retention ponds (RP) are
risk management tools that have been proposed to reduce the contaminant risk from
agricultural NPS runoff into estuarine ecosystems. Field studies were conducted
at three sites within coastal estuarine ecosystems of South Carolina (SC) from
1985 to 1990 that varied in terms of the amount and degree of risk reduction
strategies employed. An intensively managed (IPM, BMP, and RP) agricultural
treatment site (TRT) was studied for pesticide runoff impacts. From 1985 to 1987,
there were minimal (some IPM and BMP) management activities at TRT, but from 1988
to 1990, TRT was managed using an intensive risk reduction strategy. A second
unmanaged agricultural growing area, Kiawah (KWA), was also studied and compared
with TRT in terms of pesticide runoff and the resulting impacts on grass shrimp
(Palaemonetes pugio) and mummichogs (Fundulus heteroclitus). A third, non
agricultural, reference site (CTL) was used for comparing results from the
managed and unmanaged agricultural sites. In situ toxicity tests and field
samples of the grass shrimp populations were conducted at each site and compared
in terms of survival and the effectiveness of current risk reduction strategies.
Significant runoff of insecticides (azinphosmethyl, endosulfan, and fenvalerate)
along with several fish kills were observed at TRT prior to the implementation of
rigorous risk reduction methods. A significant reduction of in stream pesticide
concentrations (up to 90%) was observed at TRT following the implementation of
strict NPS runoff controls, which greatly reduced impacts on estuarine fish and
shellfish. At the unmanaged KWA, continued impacts due to the runoff of these
insecticides were observed, along with several fish kills. Additional monitoring
indicated that gravid female grass shrimp populations from KWA had elevated
levels of P-glycoprotein (P-gp), a multidrug resistance protein, which may
transport various pesticides across cellular membranes. Comparison of field
results with laboratory toxicity tests established that pesticide exposure was
the primary cause of observed field impacts at each site. These findings clearly
indicate the value of an integrated risk reduction strategy (BMP, IPM, and RP)
for minimizing impacts from NPS agricultural pesticide runoff.
PMID- 10188204
TI - Organochlorine compounds in subtropical and tropical marine organisms: a meta
analysis.
AB - A search of the published and unpublished literature was conducted for analytical
data on organochlorine compounds in tissues of subtropical and tropical marine
organisms. The search was limited to reports of analyte concentrations in whole
body or muscle tissue that were minimally determined by chromatographic
procedures. A total of 1564 sample analyses consisting of 4431 analyte
determinations were obtained for hard and soft corals, sponges, benthic
seagrasses and algae, gastropods, fish and shellfish, and 'market-basket'
(processed seafood) samples. For comparative purposes, data that were reported on
a wet- or fresh-weight basis were uniformly converted to a common dry-weight
estimate by dividing the wet-weight values by five (i.e., 80% water, 20% dry
weight tissue). Due to the large variation in analytical procedures, target
analytes, chromatographic interpretations, and reporting units, the data were
pooled by organochlorine-compound class (i.e., chlorinated cyclodienes,
chlorinated aliphatics, chlorinated phenols, and chlorinated terpenes,
hexachlorocyclohexanes, and polychlorinated biphenyls). A meta-analysis of the
resulting database yielded a mean analyte concentration of 1594 +/- 8768 ng g-1
(dry weight), a median concentration of 23 ng g-1 (dry weight), and a mean of
2.89 analytes per sample; the corresponding mean tissue burden is 4608 ng g-1
(dry weight), the equivalent of 922 ng g-1 on a wet-weight basis. It was also
found that the chlorinated aliphatics (i.e., DDT and its metabolites) constituted
40.15% of the reported analyte determinations.
PMID- 10188205
TI - An introduction to ALS-inhibiting herbicides.
AB - Herbicides that inhibit acetolactate synthase (ALS), the enzyme common to the
biosynthesis of the branch-chain amino acids (valine, leucine, and isoleucine),
affect many species of higher plants as well as bacteria, fungi, yeasts, and
algae. The novel mechanism of action attributed to ALS inhibitors, their effect
on the reproduction of some plant species, their potency at extremely low
concentrations, and the rapid evolution of resistance to these herbicides in some
plants and microorganisms are characteristics that set ALS inhibitors apart from
their predecessors. This class of chemicals affects seedling growth. Older plants
exhibit varied signs of malformation, stunting, and reduced seed production.
These herbicides are so potent that they can affect plants at levels that are
undetectable by any standard chemical protocol. Weeds quickly become resistant to
ALS inhibitors, presumably because these herbicides have a single mode of action
and because many have long residual activity. Concern now is directed towards
developing the technology to detect very low concentrations of ALS inhibitors in
the environment and their indirect effects on plant and animal health.
PMID- 10188206
TI - Pesticide use in the U.S. and policy implications: a focus on herbicides.
AB - This article examines herbicide use in the United States, providing estimates of
poundage, land surface covered, distribution, and recent trends based on federal
and state figures. Herbicides are by far the most widely used class of pesticide
in the US, where 556 million lbs of herbicide active ingredients (AIs) were
applied in 1995. Agriculture accounts for the majority of herbicide use, totaling
461 million lbs of AIs in 1995. Over 60% of the poundage of all agricultural
herbicides consist of those that are capable of disrupting the endocrine and/or
reproductive systems of animals. In addition, at least 17 types of 'inert
ingredients,' which can equal 90% or more of a pesticide product, have been
identified as having potential endocrine-disrupting effects. Atrazine is the
predominant herbicide used according to poundage, with 68-73 million lbs of AIs
applied in 1995. However, 2,4-D is the most widespread herbicide, covering 78
million acres for agricultural uses alone. Both of these herbicides are reported
endocrine disruptors. Acetolactate synthase (ALS) inhibitors, namely the
sulfonylureas and imidazolinones, are one of the fastest growing classes of
herbicides. Many of these herbicides are 100 times more toxic to select plant
species than their predecessors, so they can be applied at rates approximately
100 times lower. Consequently, they can affect plant species at concentration
levels so low that no standard chemical protocol can detect them. Due in part to
these more potent herbicides, the poundage of herbicides used in the US has
decreased since the mid-1980s; however, the available data suggest that the
number of treated acres has not significantly declined. A thorough assessment of
potential exposure to herbicides by wildlife and humans is limited due to the
inaccessibility of production and usage data.
PMID- 10188207
TI - [Prion diseases and blood transfusion].
PMID- 10188208
TI - Role of the 37 kDa laminin receptor precursor in the life cycle of prions.
AB - Prions are thought to consist of infectious proteins that cause, in the absence
of detectable nucleic acid, a group of fatal neurodegenerative diseases, called
transmissible spongiform encephalopathies (TSE). Among these diseases are bovine
spongiform encephalopathy (BSE), scrapie of sheep and Creutzfeldt-Jakob disease
(CJD) in humans. They occur as sporadic, infectious or genetic disorders and have
in common the accumulation of an abnormal, pathogenic isoform of the cellular
prion protein PrPc which is converted in a post-translational process into PrPSc
concomitant with conformational changes of the protein. During this process PrPc
acquires a high beta-sheet content and becomes partially resistant to proteases.
The mechanism of this conversion as well as the physiological function of the
cellular prion protein PrPc are poorly understood, but studies employing PrP
knock-out mice demonstrated that PrPc is required for the development of prion
diseases. The involvement of co-factors such as chaperones, receptors or an
unknown protein, designated "protein X" in the conversion process are discussed.
In a yeast two-hybrid screen we have identified the 37 kDa laminin receptor
precursor (LRP) as an interactor of the cellular prion protein and this
interaction could be confirmed by co-infection and co-transfection studies in
mammalian and insect cells. LRP evolved from the ribosomal protein p40 essential
for protein synthesis lacking any laminin binding activity to a cell surface
receptor binding laminin, elastin and carbohydrates. The gene encoding 37 kDa
LRP/p40 has been identified in a variety of species including the sea urchin
Urechis caupo, Chlorohydra viridissima, the archaebacterium Haloarcula
marismortui, the yeast Saccharomyces cerevisiae as well as in mammals where it is
highly conserved. LRP works as a receptor for alphaviruses and is associated with
the metastatic potential of solid tumors where it was first identified. The 37
kDa LRP forms its mature 67 kDa isoform with high laminin binding capacity by an
unknown mechanism involving acylation. The multifunctionality of LRP as a
ribosomal protein and a cell surface receptor for infectious agents such as
viruses and prions might be extended by additional properties.
PMID- 10188209
TI - A crucial role for B cells in neuroinvasive scrapie.
AB - Although prions are most efficiently propagated via intracerebral inoculation,
peripheral administration has caused kuru [Gajdusek et al, 1966], iatrogenic
Creutzfeldt-Jakob disease (CJD) [Gibbs et al, 1997], bovine spongiform
encephalitis (BSE), and new variant CJD [Hill et al, 1997; Bruce et al, 1997].
Neurological disease after peripheral inoculation depends on prion expansion
within cells of the lymphoreticular system (LRS) [Lasmezas et al. 1996; Wilesmith
et al, 1992]. In order to identify the nature of the latter cells, we inoculated
a panel of immune deficient mice with prions intraperitoneally. While defects
affecting only T lymphocytes had no apparent effect, all mutations affecting
differentiation and responses of B lymphocytes prevented development of clinical
scrapie. Since absence of B cells and of antibodies correlates with severe
defects in follicular dendritic cells (FDCs), the lack of any of these three
components may prevent clinical scrapie. Yet, mice expressing immunoglobulins
exclusively of the M subclass without detectable specificity for PrPc, and mice
with differentiated B cells but lacking functional FDCs, developed scrapie after
peripheral inoculation: therefore, differentiated B cells appear to play a
crucial role in neuroinvasion of scrapie regardless of B-cell receptor
specificity.
PMID- 10188210
TI - [Prion diseases and blood transfusion].
AB - Prion diseases are lethal disorders, some of which are transmissible by
infectious route. Experimental data concerning neuroinvasion indicate that there
is a viremia during the migration of the prion agent to the central nervous
system. The possibility of accidental transmission via blood products and
therefore potential transfusion risk thus arises. The analysis of experimental
and epidemiological data available at present contributes to the following
conclusion: the potential and theoretical risk for contamination from blood
products is not null but mathematically very low, there is no indisputable
experimental proof for that risk via systemic route and no case is definite and
the risk is probably linked to leukocytes, and especially B lymphocytes. These
conclusions are reassuring but nevertheless justify strict epidemiological survey
and a reasonable discussion for each transfusion. Some groups of people have to
be excluded from blood donors.
PMID- 10188211
TI - [Vectors and environmental factors in malaria].
AB - Malaria is a major risk for more than two billion human beings on Earth, and is
the cause of 700,000 to 2.5 million deaths per year. The causative factor,
Plasmodium (four species), involves an asexual cycle in man and a sexual one in
anopheline mosquitoes. The four species of Plasmodium are pathogenic for man but
P. falciparum accounts for more than 90% of deaths. Only black Africans are
refractory to P. vivax, a characteristic linked to the lack of Duffy antigen.
Among the 400 species of anophelines so far recorded, less than 50 are recognized
malaria vectors. Every one has its own geographic and ecological characteristics,
which locally induce the epidemiological trends and its biodiversity. In a given
site transmission depends on competent anopheline species, their infective rate
and their biting rate. Inhabitants of endemic areas develop during infancy
immunity which protect them during the rest of their lives. This immunity
(premunition) between parasite and its host is acquired at an heavy price of
infant mortality. It can decrease rapidly when people leave endemic areas.
Because inhabitants of endemic areas continue to harbor asymptomatic parasites
they become good parasite reservoirs. The diversity of epidemiological situations
needs a diversification of malaria control measures. The prognosis of the
evolution of malaria depends on control measures, applied or not, and on the
evolution of climatic and anthropic environment, which are very hard to predict
for the time being.
PMID- 10188212
TI - [Molecular analysis of Plasmodium falciparum infections in man].
AB - Plasmodium falciparum diversity has been analysed in two Senegalese villages with
different transmission conditions and distinct kinetics of immunity acquisition.
A very large allelic polymorphism was observed in both villages, with a similar
number of alleles but quite distinct allelic frequencies, indicating a
substantial micro-geographical heterogeneity of malaria parasite populations. In
addition, the molecular characteristics of the infections differed in both
villages. As in most endemic areas, many infected subjects carry multiple
parasite clones. In Dielmo, the number of distinct clones hosted decreases at the
age of acquisition of an efficient immunity. There was no influence of age on the
number of clones hosted in Ndiop where adults experience clinical attacks. This
indicates that complexity reflects acquired immunity. The precise longitudinal
follow-up of parasitaemia, clinical signs and parasite genetic characteristics
showed a rapid turn over of parasite populations in the peripheral blood during
the transmission season, suggesting that immunity does not prevent infection but
restricts multiplication of numerous genotypes at the erythrocytic stage.
Clinical malaria occurs after a rapid, apparently unrestricted growth of recently
inoculated parasites. The successive clinical attacks experienced by children are
associated with genotypes different for each attack and different from those that
the child carried during preceding asymptomatic phases. These data indicate that
parasite diversity contributes to the pathology of infection and that control of
parasite density, which is at least in part strain-specific, is an essential
element of protection against malaria clinical attacks.
PMID- 10188213
TI - [Creutzfeldt-Jakob disease and transfusional risk: the point in 1998].
AB - As both iatrogenic and experimental transmission of Creutzfeldt-Jakob disease
(CJD) have been demonstrated, potential blood transfusion-related CJD through
blood component contamination is not unlikely. Recent studies also suggest that B
lymphocytes would play a crucial role in the disease pathogenesis. However, to
date, there is no epidemiological evidence suggesting that classical transmission
of CJD would involve B lymphocytes. To reduce the theoretical risk of such
transmission and as no biological marker of the disease is currently available,
at-risk blood donors are excluded and leukocyte depletion has been introduced.
Furthermore, the recent discovery of a new variant of the disease (nwCJD) which
is caused by the bovine agent and has typical tropism for lymphoreticular tissues
should lead to close surveillance.
PMID- 10188214
TI - [From malaria to post-transfusional malaria].
AB - Malaria is still a blood transmissible disease, though its frequency is
continuously decreasing in non endemic countries. In endemic areas, the number of
infected subjects is either stable or increasing, depending on the involved
country. Cases of imported malaria, particularly malaria due to Plasmodium
falciparum, are increasing in France. In regard to prevention in blood donors,
regulations aiming at excluding potentially contaminated donors were implemented
with positive effects. Since 1994, no cases of malaria have been reported by the
French organization of hemovigilance.
PMID- 10188215
TI - [A short lexicon on molecular genetics].
PMID- 10188216
TI - [Apoptotic cell death in rat embryo fibroblasts transformed by EiA + cHa-RAS
oncogenes after gamma irradiation].
AB - A mechanism of apoptotic death of normal rat embryo fibroblasts and of those
transformed by E1A + cHa-Ras oncogenes following gamma irradiation has been
investigated. The E1A + cHa-Ras transformed cells were shown to express wild type
p53 which was able to trans-activate a reporter pG13-luc Plasmid. As a result of
trans-activation, an accumulation of universal inhibitor of cyclin-dependent
kinases--p21/Waf1 protein and an increase in the proportion of p21/Waf1
expressing cells were observed, The accumulated p21/Waf1 was found to bind with
PCNA. The association with PCNA, however, did not lead to suppression of DNA
replication according to the data of iododeoxyuridine (IdUr) incorporation. A
high proportion of S-phase cells, in combination with cell cycle blocking in G2
phase, promoted polyploidization of E1A + cHa-Ras transformed cells after gamma
irradiation. The polyploidic cells with DNA content equal and higher than 8c die
48-72 h following irradiation due to apoptosis. A significant proportion of E1A +
cHa-Ras cells with incorporated IdUr contains labeled micronuclei, the fact being
a morphological evidence of apoptosis of cells in S-phase of the cell cycle.
PMID- 10188217
TI - [Modelling of myocardial hypertrophy in vitro for solving problems of medicinal
correction].
AB - The work has been done on primary heart culture from neonatal rat ventricle.
Cardiomyocyte hypertrophy was modelled using noradrenaline (NA), angiotensin II
(AII) and fetal serum, respectively. Cell hypertrophy of primary heart cultures
was assessed by measuring the surface area, the scope of protein synthesis
estimated by 3H-leucine autoradiography and the contents of nucleic acids in
gallocyanin-chromalum stained cardiomyocytes. The structure of myofibrillar
apparatus was studied by rhodamine-conjugated phalloidin and indirect
immunofluorescence of muscle alpha-actinin. Treatment with 10(-6) M NA increased
3H-leucine incorporation in 9-day old heart culture by 42% without changing cell
size. AII in a dose 1 microM stimulated protein synthesis activity by 1.3 fold
and the surface area by 1.7 fold, both in 2- and 9-day old primary heart
cultures. The maximum stimulation of cell hypertrophy was provided by the medium
supplemented with fetal serum. RNA contents in the cytoplasm of cardiomyocytes
increased by 7.8 fold and the myocardial cell size by 2.9 fold in serum
supplemented culture by 9 days of cultivation. In the medium with fetal serum,
amounts of cardiomyocytes with tetraploid nuclei reached 33%, against 14% in
control. Coculturing of myocardiocytes and fibroblasts rendered effects of fetal
serum on the growth of myocardiocytes. Cultivation in the presence of 1 microM
enalapril, an ACE inhibitor, suppressed the development of cardiac muscle cells
hypertrophy. The effect of enalapril depended on the degree of cellular
hypertrophy. Addition of 10 microM amiloride to the medium lowered the protein
synthesis by 29% independently on the initial cellular hypertrophy.
PMID- 10188218
TI - [Effects of extracellular matrix elements on pseudopodial activity of rat
keratinocytes].
AB - Effects of extracellular matrix elements on the migration activity of
keratinocytes have been studied in the primary culture obtained from newborn
rats. Collagen of type I, matrigel, its fractions and the matrix produced by
fibroblasts were used as substrata for cultivation. A method of migration
activity estimation using latex spheres 0.8 mkm in diameter was first used. We
have revealed that keratinocytes from the primary culture do not migrate on
matrigel and fibroblast matrix, though displaying some pseudopodial activity.
This activity dramatically increases on type I collagen, and a weak migration
ability appears correlating with a particular structure of the actin
cytoskeleton, i.e. with the appearance of special lamellopodia-connected
filopodia.
PMID- 10188219
TI - [Induction of cell adhesion molecules, E-selectin, VCAM-1 and ICAM-1, in a co
culture of human endothelial and smooth muscle cells].
AB - Using immunofluorescence and flow cytometry, we studied the surface expression of
cell adhesion molecules, E-selectin, VCAM-1 and ICAM-1, in human umbilical vein
endothelial cells (HUVEC) co-cultured with human aortic intimal smooth muscle
cells (SMC). It was found that inactivated HUVEC constitutively expressed only
ICAM-1. After 3-4 h of co-culturing with SMC in the Transwell system we observed
the appearance of E-selectin and VCAM-1, and the increase of ICAM-1 content on
the cell surface. In all the cases, the maximum expression of these molecules (85
100% of positively stained cells) was detected within 18-24 h after co-culturing.
Similar effect was exerted by SMC-conditioned culture medium, whose action well
compared with that of a direct addition of interleukin-1 to EC at a concentration
of 5-10 u/ml. The obtained data suggest that the cytokines secreted by SMC may
participate in the regulation of endothelial cell adhesion molecule expression,
and influence cell accumulation in sites of inflammation, immune disorders, etc.
PMID- 10188220
TI - [The stat pathway in intracellular signalling].
AB - This review summarises the main approaches in investigations concerning the
recently characterised signalling pathway, including STAT family proteins. The
perspective strategies to study biological functions of STATs, having a dual
function, as signal molecules and transcription factors, are discussed.
PMID- 10188221
TI - [Proteins of the Stat family: role in cell signalling].
AB - This review is devoted to the participation of STATs in cell signalling. A great
attention is paid to the mechanisms of STATs activation and cross-talking of STAT
pathway of signal transduction with others. The role of STATs in cell
proliferation, differentiation, apoptosis and transformation is discussed.
PMID- 10188222
TI - [Intact microtubule network is necessary for the EGF-induced transport of
transcription factor STAT1 in the nucleus of A-431 cells].
AB - The mechanism by which transcription factor STAT1 is translocated from the
cytoplasm to the cell nucleus is not clear. We put forward a hypothesis
suggesting an important role of the cytoskeleton in signal transduction. The
results of the present work show that the treatment of cells with nocodazole, a
microtubule-disrupting drug, inhibits completely STAT1 import to the nucleus.
However, the treatment of cells with cytochalasin B, which is known to
depolymerize microfilaments, exerted no detectable effect on the transport of
STAT1. The sensitivity to nocodazole treatment suggests that STAT1 may utilize a
transport pathway that involves the tubulin cytoskeleton. These data throw light
on some mechanism of a rapid and effective nonvesicular transport of STAT1.
PMID- 10188223
TI - [The transcription factor STAT3 is associated with elements of the cytoskeleton
in A-431 cells].
AB - The transcription factor STAT3 (signal transducers and activators of
transcription) takes part in cell signaling. Here we show that STAT3 is
associated with the cytoskeleton in A-431 cells. The protein is determined in
cytoskeletal (detergent insoluble) fraction of control cells and of cells after
RGF treatment. STAT3 is diffusely distributed in the cytoplasm of control cells
to be seen relocalized to the nuclei after EGF treatment. Besides, the protein is
observed in cell membrane protrusions. Using double immunofluorescence, co
localization of action and STAT3 was shown in these structures.
PMID- 10188224
TI - [Transcription factors STAT1 and STAT3 are localized in different compartments of
rat embryo fibroblasts transformed by E1A and Ha-Ras oncogenes].
AB - Intracellular distribution of STAT1 and STAT3 transcription factors in normal
fibroblasts (REF) and in E1A + Ha-Ras transformed cells has been studied by means
of indirect immunofluorescence. The obtained data evidence that in REF cells, in
response to the growth factor addition, STAT1 and STAT3 proteins are
redistributed from the cytoplasm to the nucleus. In transformants E1A + Ha-Ras,
however, significantly different pictures can be seen: while STAT1 is found to be
constitutively localized in the cell nuclei, STAT3 is predominantly revealed in
the cytoplasm. The data obtained from fractionation of subcellular structures
confirm in general the immunofluorescence results on the cytoplasmic localization
of STAT3 protein in E1A + Ha-Ras transformants. Thus, transformation of REF cells
with E1A + Ha-Ras oncogenes causes a constitutive activation of STAT1 and STAT3
transcription factors, the proteins, however, being distributed in different cell
compartments.
PMID- 10188231
TI - [Correlation of anticholinesterase activity of reversible peralkylated onium
inhibitors of various acetylcholinesterases and geometric parameters of their
molecules].
PMID- 10188232
TI - [Composition and properties of serum proteins from the Greenland seal Pagophilus
groenlandica pups during adaptation to captivity].
PMID- 10188233
TI - [Functional maturation of the white mouse motor neocortex during early postnatal
ontogenesis].
PMID- 10188234
TI - [Activity of Purkinje cells from the cerebellum of young and adult rats during
hypercalcemia].
PMID- 10188235
TI - [Effect of calcitonin gene-related peptide on lymphatic vessels].
PMID- 10188237
TI - [Effect of acetazolamide on sodium and potassium absorption from the rumen of the
reindeer Rangifer tarandus].
PMID- 10188236
TI - [Interaction between vasopressinergic cells of the hypothalamus neurosecretion
centers and the thyroid gland in rats].
PMID- 10188238
TI - A comparative analysis of the citrate permease P mRNA stability in Lactococcus
lactis biovar diacetylactis and Escherichia coli.
AB - The role of ribonucleases in the control of gene expression remains unknown in
lactic acid bacteria. In the present work, we analysed the expression of the citP
gene, which encodes the lactococcal citrate permease P, through the stability of
the citQRP messenger in both Lactococcus lactis biovar diacetylactis (L.
diacetylactis) and Escherichia coli. The chemical half-life for citQRP mRNA
observed in L. diacetylactis wild-type strain was abnormally long for bacteria.
It was even longer than that detected in E. coli RNase E or RNase III mutant
strains. A model of processing and fate of RNA species containing citP gene is
presented.
PMID- 10188239
TI - Role of intracellular calcium in Pasteurella haemolytica leukotoxin-induced
bovine neutrophil leukotriene B4 production and plasma membrane damage.
AB - Isolated neutrophils were used to study the intracellular calcium ([Ca2+]i)
dependency of Pasteurella haemolytica leukotoxin-induced production of
leukotriene B4 and plasma membrane damage. Exposure of neutrophils to leukotoxin
caused a rapid and concentration-dependent increase in [Ca2+]i, followed by
simultaneous plasma membrane damage and production of leukotriene B4. Removal of
extracellular Ca2+, replacement of Ca2+ with other divalent cations, or exposure
to high concentration of verapamil, an inhibitor of voltage-dependent calcium
channels, inhibited leukotoxin-induced increases in [Ca2+]i, leukotriene B4
production, and membrane damage, thus indicating that influx of extracellular
Ca2+ is necessary to produce these leukotoxin-induced neutrophil responses.
PMID- 10188240
TI - Transformation of a type 4 encapsulated strain of Streptococcus pneumoniae.
AB - Streptococcus pneumoniae strain JNR.7/87 is a highly virulent, type 4
encapsulated Gram-positive bacterium whose transformability has not been tested
previously, and whose genome is currently being sequenced. The strain was
transformed at very low efficiency by addition of exogenous competence
stimulating peptide: However, the efficiency was too low and irreproducible to be
useful in many genetic studies. Therefore, the effects on transformation
efficiency of changing different components of competence-stimulating peptide
induced transformation have been examined. Screening of growth media was followed
by optimization of pre-induction culture acidification, glycine concentration,
and induction time. An optimized protocol was developed whereby S. pneumoniae
strain JNR.7/87 was transformed reproducibly with a streptomycin resistance (SmR)
marker at an efficiency of approximately 10(5) colony forming units per 10(8)
cells.
PMID- 10188241
TI - Analysis, expression and prevalence of the Mycobacterium tuberculosis homolog of
bacterial virulence regulating proteins.
AB - We have previously reported the identification of a gene from Mycobacterium
tuberculosis, H37Rv, which on the basis of its nucleotide sequence encoded a
protein product of 38 kDa. This 38-Kda mycobacterial protein designated as VirS
exhibits homology with the VirF protein of Shigella, the VirFy protein of
Yersinia and the Cfad, Rns and FapR proteins from various enterotoxigenic
Escherichia coli strains. In this communication, we show the close sequence and
structural similarities of the VirS protein with VirF, VirFy, Cfad, Rns and FapR
and describe the results of our studies on the characterization of the virS gene
promoter and its expression in E. coli and mycobacteria. virS was present
exclusively in the species belonging to the M. tuberculosis complex as revealed
by Southern blot and PCR analysis. Our findings suggest the involvement of virS
in the regulation of pathogenesis of M. tuberculosis.
PMID- 10188242
TI - Clonal relationship among invasive and non-invasive strains of enteroinvasive
Escherichia coli serogroups.
AB - The genetic relatedness among 96 invasive Escherichia coli belonging to several
serogroups and 13 non-invasive of several serotypes that share the same O antigen
was investigated by multilocus enzyme electrophoresis analysis. The invasive
strains were isolated in different parts of the world and most of them recovered
from dysentery. Twenty-nine electrophoretic types were distinguished and the most
invasive strains were found to belong to two major lineages. These results
suggested that the invasive ability in these strains has evolved in divergent
chromosomal backgrounds, presumably through the horizontal spread of plasmid
borne invasion genes. The maintenance of invasive phenotypes in separate lineages
suggests that this ability confers a selective advantage to invasive strains.
PMID- 10188243
TI - A new gene, sigG, encoding a putative alternative sigma factor of Streptomyces
coelicolor A3(2).
AB - An oligonucleotide probe encoding a peptide motif conserved in all sigma factors
was used to isolate a new gene, sigG, from a Streptomyces coelicolor A3(2)
genomic library. The deduced protein of 263 amino acids with an M(r) of 29,422
showed the greatest similarity to the previously identified sporulation sigma
factor (sigma F) of Streptomyces coelicolor, and general stress response sigma
factor (sigma B) of Bacillus subtilis, mostly in domains suggested to be involved
in recognition of -10 and -35 promoter regions. Southern-blot hybridization with
DNA from several Streptomyces spp. revealed the presence of a similar gene in all
strains tested. Disruption of the S. coelicolor sigG gene appeared to have no
obvious effect on growth, morphology, differentiation, and production of
pigmented antibiotic actinorhodin and undecylprodigiosin.
PMID- 10188244
TI - Survival of Salmonella enteritidis and Salmonella typhimurium in chicken manure
at different levels of water activity.
AB - Survival of Salmonella enteritidis and Salmonella typhimurium in chicken manure
at different levels of water activity (aw) was determined. The aw was adjusted by
means of saturated salts with defined equilibrium relative humidity and the
manure samples were stored aerobically at 20 degrees C. At aw levels higher than
0.93, a moderate increase in colony-forming units over 8-9 h was found for both
strains; at aw levels of 0.89-0.75, there was a thousand-fold reduction. Extended
storage resulted in a million-fold reduction of Salmonella enteritidis in 8 days
at an aw of 0.89. At higher and lower levels of aw, the reduction was less
extensive.
PMID- 10188245
TI - Localization of DnaK and GroEL in Vibrio cholerae.
AB - Though the GroEL and DnaK heat shock proteins are well characterized in
prokaryotes, only scanty and controversial information exist about their cellular
localization. In the present study, the localization of the heat shock proteins
DnaK and GroEL in normal and heat shocked cells of Vibrio cholerae, was
investigated both by immunogold labeling of ultrathin sections and biochemical
methods. Much of the DnaK was found to be localized at the inner membrane in
unstressed cells, most probably at the Bayer's adhesion sites. Data suggested
that upon heat shock, the DnaK associated with the membrane continued to remain
there, but the newly synthesized DnaK appeared mostly in the cytoplasm. GroEL in
both stressed and unstressed cells was found mainly in the cytoplasm.
PMID- 10188246
TI - Shift-down in growth rate rather than high cell density induces toxic shock
syndrome toxin-1 gene expression in Staphylococcus aureus.
AB - A luciferase-based reporter system for the expression of the toxic shock syndrome
toxin-1 gene (tst) of Staphylococcus aureus FRI 1187 was used in continuous
culture to determine whether high cell density on transient shift-down or shift
up of specific growth rate (mu) induced expression of tst. Little expression
occurred at steady state at a low dilution rate (D) and in a transient period of
increasing mu. However, a rapid and approximately 130-fold increase in expression
occurred during a transient shift-down of mu. These findings suggest reduction of
mu is a key element in the control of tst expression.
PMID- 10188247
TI - Cloning and characterization in Escherichia coli of the gene encoding the
principal sigma factor of an extreme thermophile, Thermus thermophilus.
AB - The nucleotide sequence of the upstream region of the aspartate kinase genes of
Thermus thermophilus HB27 revealed the presence of two open reading frames in the
orientation opposite to that of the aspartate kinase genes. The upstream open
reading frame termed ORF375 encodes a protein composed of 375 amino acid
residues, possessing amino acid sequence motifs for methylases. Another open
reading frame designated as sigA encodes a protein of 423 amino acid residues
which shows significant identity in amino acid sequence to the principal sigma
factor, a component of the DNA-dependent RNA polymerase holoenzyme. The close
proximity of the open reading frames suggested that the two genes are transcribed
in a polycistronic manner. By the use of an Escherichia coli expression system,
SigA was produced in a soluble form. An in vitro transcription assay of purified
SigA reconstituted with the core RNA polymerase of E. coli showed that Thermus
SigA functioned as a sigma factor to initiate specific transcription.
PMID- 10188248
TI - Self-assembly product formation of the Bacillus stearothermophilus PV72/p6 S
layer protein SbsA in the course of autolysis of Bacillus subtilis.
AB - In order to achieve high level expression and to study the release of a protein
capable of self-assembly, the gene encoding the crystalline cell surface (S
layer) protein SbsA of Bacillus stearothermophilus PV72/p6, including its signal
sequence, was cloned and expressed in Bacillus subtilis. To obtain high level
expression, a tightly regulated, xylose-inducible, stably replicating multicopy
plasmid vector was constructed. After induction of expression, the S-layer
protein made up about 15% of the total cellular protein content, which was
comparable to the SbsA content of B. stearothermophilus PV72/p6 cells. During all
growth stages, SbsA was poorly secreted to the ambient cellular environment by B.
subtilis. Extraction of whole cells with guanidine hydrochloride showed that in
late stationary growth phase cells 65% of the synthesised SbsA was retained in
the peptidoglycan-containing layer, indicating that the rigid cell wall layer was
a barrier for efficient SbsA secretion. Electron microscopic investigation
revealed that SbsA release from the peptidoglycan-containing layer started in the
late stationary growth phase at distinct sites at the cell surface leading to the
formation of extracellular self-assembly products which did not adhere to the
cell wall surface. In addition, intracellular sheet-like SbsA self-assembly
products which followed the curvature of the cell became visible in partly lysed
cells. Intracellularly formed self-assembly products remained intact even after
complete lysis of the rigid cell envelope layer.
PMID- 10188249
TI - Ferric-reductase activities in Vibrio vulnificus biotypes 1 and 2.
AB - In this paper, the ferric-reductase activities of Vibrio vulnificus were
investigated. This species comprises two biotypes pathogenic for humans and eels
that are able to express different mechanisms for iron acquisition. All strains
of both biotypes used in this study were able to reduce ferric citrate,
irrespective of the iron levels in the growth medium. Some variation in the
degree of reduction was observed among the strains, with the highest values
corresponding to one acapsulated environmental strain of biotype 1. When cell
fractions were tested, only those from periplasm and cytoplasm showed reductase
activity whereas no activity was detected in membranes. Low temperatures
inhibited these activities in both whole cells and cell fractions. At least six
bands with ferric-reductase activity were identified in all strains using native
polyacrylamide gels. These data demonstrate that the two biotypes of V.
vulnificus produce similar ferric-reductases mainly located in the periplasm and
cytoplasm and these could be involved in iron acquisition.
PMID- 10188250
TI - Arthrospira ('Spirulina') strains from four continents are resolved into only two
clusters, based on amplified ribosomal DNA restriction analysis of the internally
transcribed spacer.
AB - We present the results of a phylogenetic study, based on amplified ribosomal DNA
restriction analysis of the rDNA operon, of 37 Arthrospira ('Spirulina')
cultivated clonal strains from four continents. In addition, duplicates from
different culture collections or markedly different morphotypes of particular
strains established as clonal cultures were treated as separate entries,
resulting in a total of 51 tested cultures. The strain Spirulina laxissima SAG
256.80 was included as outgroup. The 16S rRNA genes appeared too conserved for
discrimination of the strains by amplified ribosomal DNA restriction analysis,
and thus the internally transcribed spacer was selected as molecular taxonomic
marker. The internally transcribed spacer sequences situated between the 16S and
the 23S rRNA were amplified by polymerase chain reaction and yielded amplicons of
about 540 bp. Direct use of cells for polymerase chain reaction seemed to inhibit
the amplification reaction. This was overcome by the design of a crude lysis
protocol and addition of bovine serum albumin in the polymerase chain reaction
mix. The amplicons were digested with four restriction enzymes (EcoRV, Hhal,
Hinfl, Msel) and the banding patterns obtained were analyzed. Cluster analysis
showed the separation of all the strains into two main clusters. No clear
relationships could be observed between this division into two clusters and the
geographic origin of the strains, or their designation in the culture
collections, or their morphology.
PMID- 10188251
TI - Cloning and characterization of a new exo-cellulase gene, cel3, in Irpex lacteus.
AB - A new cellulose-inducible gene (named cel3) was isolated from a strain of the
white rot basidiomycete, Irpex lacteus MC-2. The cel3 open reading frame,
containing two introns, encodes a polypeptide of 526 amino acids residues with a
molecular mass of 55794 Da. Expression of the cel3 gene was induced by various
insoluble celluloses and CM-cellulose. Transcription of cel3 was abolished when
cells were cultivated in media containing the above cellulosic substrates, but
added with glucose, fructose or lactose, while addition of glycerol or mannitol
did not affect the cel3 mRNA level. The amino acid sequence of the catalytic
domain of the Cel3 protein was homologous to that of fungal exo-type cellulases
belonging to family 7 of the glycosyl hydrolases. A phylogenetic study showed
that these exo-type cellulases can be clearly separated from family 7 endo-type
cellulases.
PMID- 10188252
TI - Signature region within the 16S rDNA sequences of Aeromonas popoffii.
AB - To identify a group of eight Aeromonas strains of our collection showing
ribotyping patterns similar to those described for the species Aeromonas
popoffii, 16S rRNA gene sequence analysis was performed. Results were in
agreement with the DNA binding values, and allowed the identification of a
'signature region' differentiating the A. popoffii strains from all other members
of the genus Aeromonas.
PMID- 10188253
TI - Antiseptic susceptibility and distribution of antiseptic-resistance genes in
methicillin-resistant Staphylococcus aureus.
AB - We examined the antiseptic susceptibilities and distribution of antiseptic
resistance genes qacA and smr in 98 isolates of methicillin-resistant
Staphylococcus aureus obtained in 1992. Seventy-one strains were resistant to
antiseptics. The qacA and smr genes were detected in 10 and 20 strains,
respectively. The remaining 41 strains without qacA and smr were divided into two
groups that exhibited low-level (n = 22) and high-level (n = 19) resistance to
acriflavin. DNA cloning and sequencing suggested that norfloxacin-resistance gene
norA was responsible for the high-level resistance to acriflavin. Our results
indicated that four or more antiseptic-resistance genes exist in methicillin
resistant S. aureus and that antiseptic-resistant methicillin-resistant S. aureus
strains without qacA and smr are widely spread in Japan.
PMID- 10188254
TI - Genetic basis of macrolide and lincosamide resistance in Brachyspira (Serpulina)
hyodysenteriae.
AB - Macrolide antibiotic resistance is widespread among Brachyspira hyodysenteriae
(formerly Serpulina hyodysenteriae) isolates. The genetic basis of macrolide and
lincosamide resistance in B. hyodysenteriae was elucidated. Resistance to
tylosin, erythromycin and clindamycin in B. hyodysenteriae was associated with an
A-->T transversion mutation in the nucleotide position homologous with position
2058 of the Escherichia coli 23S rRNA gene. The nucleotide sequences of the
peptidyl transferase region of the 23S rDNA from seven macrolide and lincosamide
resistant and seven susceptible strains of Brachyspira spp. were determined. None
of the susceptible strains were mutated whereas all the resistant strains had a
mutation in position 2058. Susceptible strains became resistant in vitro after
subculturing on agar containing 4 micrograms ml-1 of tylosin. Sequencing of these
strains revealed an A-->G transition mutation in position 2058.
PMID- 10188255
TI - Polar tube proteins of microsporidia of the family encephalitozoonidae.
AB - Encephalitozoonidae are microsporidia associated with human infections including
hepatitis, encephalitis, conjunctivitis, and disseminated disease. Microsporidia
produce a small resistant spore containing a polar tube which serves as a unique
vehicle of infection. Polar tube proteins (PTPs) from Encephalitozoon hellem.
Encephalitozoon (Septata) intestinalis, and Encephalitozoon cuniculi were
purified to homogeneity by HPLC. By SDS-PAGE, the Mr of E. hellem PTP was 55 kDa,
while the Mr of E. intestinalis and E. cuniculi PTP was 45 kDa. Polyclonal rabbit
antiserum to these purified PTPs localized to polar filaments by immunogold
electron microscopy and immunofluorescence, and demonstrated cross-reactivity by
both immunoblotting and immunogold electron microscopy. These PTPs have similar
solubility properties, hydrophobicity, and proline content to a 43-kDa PTP we
have previously purified from Glugea americanus, a fish microsporidium. As the
polar tube is critical in the transmission of this organism, further study of
PTPs may lead to the development of new therapeutic strategies and diagnostic
tests.
PMID- 10188256
TI - Interface-mediated death of unconditioned Tetrahymena cells: effect of the medium
composition.
AB - We have previously shown that the cell death of Tetrahymena thermophila in low
inocula cultures in a chemically-defined medium is not apoptotic. The death is
caused by a cell lysis occurring at the medium-air interface and can be prevented
by the addition of insulin or Pluronic F-68. Here, we report that cell death can
also be caused by the medium. The specific effects of several medium constituents
were tested in the presence and absence of an interface. Four of the 19 amino
acids (arginine, aspartic acid, glutamic acid, and histidine in millimolar
concentration) as well as Ca2+ (68 microM) and Mg2+ (2 mM) and trace metal ions
(micromolar concentrations) are all sufficient to induce the interface-mediated
death. The effect of the amino acids and the salt ions Ca2+ and Mg2+ can be
abolished by the addition of insulin (10(-6) M) or Pluronic F-68 (0.01% w/v),
whereas insulin/Pluronic F-68 only postpones the death induced by trace metal
ions. On the basis of our findings, a new recipe for a chemically-defined medium
has been formulated. Single cells can grow in this medium in the presence of
medium-air interface without any supplements.
PMID- 10188257
TI - Polymorphisms at the topoisomerase II gene locus provide more evidence for the
partition of Trypanosoma cruzi into two major groups.
AB - We have dissected the topoisomerase II gene of members of the two recently
characterized subgroups of Trypanosoma cruzi to obtain further evidence to
support this dichotomy of isolates in this important parasite. Pulsed field gel
electrophoresis showed a striking heterogeneity in the molecular karyotypes of
the strains analyzed. Southern analysis of these chromosome gels also showed
heterogeneity in the size and number of chromosomes containing the topoisomerase
II gene. Analysis of DNA restriction fragment length polymorphisms of the
topoisomerase II gene also showed two principal patterns consistent with the two
previously characterized groups. Finally, the sequences of portions of the
topoisomerase II genes from members of the T. cruzi groups showed two distinct
patterns, again consistent with the previous grouping of this parasite. Thus,
this work clearly supports previous observations suggesting an ancient divergence
of known T. cruzi isolates into two main branches.
PMID- 10188258
TI - Vanadate affects nuclear division and induces aberrantly-shaped cells during
subsequent cytokinesis in Tetrahymena.
AB - Sodium orthovanadate at 0.1-5.0 mM affected cell proliferation of Tetrahymena in
a dose-dependent manner. At 1 h the cell increment was 76-12% of the control
(100%), but after lag periods in 1-5 mM the growth rate remained at 76% of
control in 0.1 mM vanadate and at 64-61% of control in 0.2-5.0 mM vanadate.
Endocytosis was affected in both a time- and dose-dependent manner; an increasing
number of cells did not form vacuoles. Cell motility increased initially in 0.1
mM vanadate but decreased later as it did in 0.5-2.0 mM vanadate where the
proportion of immobile cells increased with time. Cell divisions occurred at all
concentrations but macronuclear elongation was disturbed and subsequent
cytokinesis resulted in daughter cells containing the entire G2 macronucleus, a
large or small portion of it, or no nucleus at all. Moreover, odd cell shapes
appeared with time. The size of the cell and nucleus increased but there was
great variation with disturbed cytoplasm/nucleus ratios. Treated cells had
dilated rough endoplasmic reticulum that included dense material, presumed to be
vanadate, which was not seen in control cells. Scant amounts of dense material
were found in dense granules, small vacuoles, and abundantly in contractile
vacuoles. It is argued that interference with proper microtubular function is the
main effect of vanadate.
PMID- 10188259
TI - Trypanosoma rangeli--in vitro metacyclogenesis and fate of metacyclic
trypomastigotes after infection to mice and fibroblast cultures.
AB - High metacyclogenesis was induced when freshly-isolated Trypanosoma rangeli from
humans were grown in a modified liver-infusion-tryptose medium and transferred
into the medium overlaid on mouse fibroblasts at 27 degrees C in a 5% CO2
atmosphere. Such in vitro-generated metacyclic trypomastigotes could induce a
significantly high and constant parasitemia in both ICR and SCID mice for a
period of about a week but thereafter the parasitemia gradually decreased.
Histological examination could not detect any tissue-forms of T. rangeli in
various organs of SCID mice. On the other hand, two long-maintained stocks of T.
rangeli produced lower metacyclogenesis and only latent parasitemia in both
strains of mice. When these populations were incubated in fibroblast cultures at
37 degrees C in a 5% CO2 atmosphere, only trypomastigotes survived for two to
three weeks without proliferation, while other forms, mainly epimastigotes, soon
began to swell and degenerate. Electron microscopy showed that most surviving
trypomastigotes had the basket-like conformation of the kinetoplasts. This is
characteristic of the non-dividing trypomastigote stage of T. cruzi, and suggests
that T. rangeli trypomastigotes may survive long periods in the blood without
proliferation.
PMID- 10188260
TI - Disturbance of the determination of germinal and somatic nuclei by heat shock in
Paramecium caudatum.
AB - During conjugation of Paramecium caudatum, nuclear determination occurs soon
after the third postzygotic division: one of the four anterior nuclei becomes the
micronucleus and the remaining three degenerate, while four posterior nuclei
differentiate into macronuclear anlagen. Macronuclear differentiation is supposed
to be dependent on a cytoplasmic differentiation factor. In this study,
postzygotic cells were subjected to heat shock for 30 min and nuclear changes
were observed by staining with carbol fuchsin solution. When heat shock was
initiated during the period from metaphase to telophase of the third postzygotic
division, cells showed an excess of macronuclear anlagen and were typically
amicronucleate. Abnormal nuclear localization around the end of the third (last)
postzygotic division may explain the origin of these kinds of cells. A similar
phenomenon appeared after treatment with actinomycin D or emetine. Since heat
shock did not inhibit macronuclear differentiation but destroyed the formation of
micronuclei, some factor(s) probably plays an essential role in nuclear
determination, especially in the protection of the micronuclei.
PMID- 10188261
TI - Transformation of Paramecium tetraurelia by electroporation or particle
bombardment.
AB - Methods for mass transformation of Paramecium tetraurelia were established using
plasmids bearing neomycin-resistance or calmodulin gene fragments. Phenotypic and
molecular analyses showed that, although variable, up to 5% transformation can be
achieved by electroporation. Concentrations of divalent cations Ca2+ and Mg2+ in
the electroporation medium were crucial for efficient transformation. Strong
neomycin-resistance transformation using bioballistic particle bombardment with
gold particles was observed. For both methods, hybridization to transformant DNA
revealed plasmid signals consistent with macronuclear transformation and
correlated with transformed phenotypes. Complementation of a known calmodulin
gene mutation was also achieved by mass transformation. Possible sources of
variation and the general utility of these methods are discussed.
PMID- 10188262
TI - Small subunit ribosomal RNA sequence of Henneguya exilis (class Myxosporea)
identifies the actinosporean stage from an oligochaete host.
AB - Several transmission studies, as well as recent molecular data, have indicated
that the two classes Myxosporea and Actinosporea represent different life cycle
stages of Myxozoa. To evaluate the life cycles of myxozoa in catfish aquaculture
systems, the small subunit (18S) ribosomal RNA gene sequences of Henneguya
exilis, a myxosporean from channel catfish Ictalurus punctatus, and an
actinosporean (previously designated as Aurantiactinomyxon janiszewskai) from the
aquatic oligochaete Dero digitata were determined. The sequences were identical,
indicating that H. exilis and the actinosporean are alternate life stages of a
single species. This is the first report identifying the actinosporean stage of
the genus Henneguya.
PMID- 10188263
TI - Evidence for early signaling events in stomatin-induced differentiation of
Tetrahymena vorax.
AB - The mechanism of stomatin-induced differentiation of Tetrahymena vorax was
investigated by in vivo protease degradation of cell surface proteins, the direct
measurement of products formed from the activation of phospholipase C, and the
use of an array of signal transduction inhibitors/activators. The data indicate
that a surface-exposed protein is required for stomatin to signal the cells to
differentiate and that the cells are committed to the differentiation pathway
within two hours after exposure to stomatin. Analysis of radiolabeled
polyphosphoinositols and inositol lipids from control and stomatin-treated
populations in the presence of 10 mM LiCl were consistent with a rapid activation
of phospholipase C. Within five min following addition of stomatin, this resulted
in an increase in polyphosphoinositols and a concomitant decrease in the relative
amounts of phosphatidylinositol bisphosphate and phosphatidylinositol
trisphosphate.
PMID- 10188264
TI - Pathological and nonpathological dissociation: the relevance of childhood trauma.
AB - Although previous research has implicated a history of childhood trauma in the
development of dissociative tendencies, insufficient cognizance (in this context)
has been taken of the distinction between pathological and nonpathological
dissociation. In this study, the relationship between childhood trauma and both
pathological and nonpathological dissociation was investigated in a sample of 100
Australian adults. Pathological dissociation was positively predicted by
dimensions of childhood trauma, but no such relationship was found for
nonpathological dissociation (psychological absorption). The data are consistent
with the traumagenic model of the dissociative disorders, but factors other than
childhood trauma may also be pertinent.
PMID- 10188266
TI - The influences of behavior valence and actor race on black and white children's
moral and liking judgments.
AB - Preschoolers, 1st graders, and 4th graders were shown line drawings that depicted
2 prosocial and 2 aggressive behaviors. Black actors or White actors were
depicted in the scenarios, and a brief description of each behavior was read to
the child. For each scenario, children rated their liking for the actor and the
morality of the actor's behavior. Findings indicated that children at each age
level significantly differentiated the actors by behavior valence for moral and
liking judgements. However, the moral judgements of White preschoolers were more
differentiated by behavior valence than the judgments of Black preschoolers.
Also, there was more differentiation of actors by behavior valence for liking
judgments as the age levels of the children increased. Black actors received more
negative moral judgments than did White actors only at the preschool level.
PMID- 10188265
TI - Further cross-cultural validation of the theory of mental self-government.
AB - This study was designed to achieve two objectives. The 1st was to investigate the
cross-cultural validity of the Thinking Styles Inventory (TSI; R. J. Sternberg &
R. K. Wagner, 1992), which is based on the theory of mental self-government (R.
J. Sternberg, 1988, 1990, 1997). The 2nd was to examine the relationships between
thinking styles as assessed by the TSI and a number of student characteristics,
including age, gender, college class level, work experience, and travel
experience. One hundred fifty-one students from the University of Hong Kong
participated in the study. Results indicated that the thinking styles evaluated
by the TSI could be identified among the participants. Moreover, there were
significant relationships between certain thinking styles, especially creativity
relevant styles and 3 student characteristics: age, work experience, and travel
experience. Implications of these findings for teaching and learning in and
outside the classroom are discussed.
PMID- 10188267
TI - The relationship between differential inequity, job satisfaction, intention to
turnover, and self-esteem.
AB - This study was an examination of differential inequity or underreward in working
conditions, originating from the discrepancy between individual working
conditions and those of comparative referents. In its exploration of the outcomes
of inequity in working conditions, the study fills a gap in the literature
because most such studies have been primarily devoted to investigations of pay
inequity. Empirically, it is an investigation of elements of differential
inequity as antecedents of job satisfaction and intentions to turnover and of
self-esteem as a moderator of inequity-criteria relationships. Significant
relationships between system and age inequity and job satisfaction and between
company inequity and intention to turnover were found. Self-esteem significantly
moderated the global inequity-job satisfaction and global inequity-intention to
turnover relationships.
PMID- 10188268
TI - Cultural background and coping with loneliness.
AB - The present study is an examination of the influence of cultural background on an
individual's ability to cope with loneliness. Participants were from 3 cultural
backgrounds: North American, South Asian, and West Indian. A total of 679
participants (318 men and 361 women) answered an 18-item loneliness
questionnaire. Results revealed significant differences in the coping strategies
that the participants used. Gender differences were also found across the
cultures and within each culture.
PMID- 10188270
TI - Rhizobium sp. strain NGR234 and R. fredii USDA257 share exceptionally broad,
nested host ranges.
AB - Genetically, Rhizobium sp. strain NGR234 and R. fredii USDA257 are closely
related. Small differences in their nodulation genes result in NGR234 secreting
larger amounts of more diverse lipo-oligosaccharidic Nod factors than USDA257.
What effects these differences have on nodulation were analyzed by inoculating
452 species of legumes, representing all three subfamilies of the Leguminosae, as
well as the nonlegume Parasponia andersonii, with both strains. The two bacteria
nodulated P. andersonii, induced ineffective outgrowths on Delonix regia, and
nodulated Chamaecrista fasciculata, a member of the only nodulating genus of the
Caesalpinieae tested. Both strains nodulated a range of mimosoid legumes,
especially the Australian species of Acacia, and the tribe Ingeae. Highest
compatibilities were found with the papilionoid tribes Phaseoleae and Desmodieae.
On Vigna spp. (Phaseoleae), both bacteria formed more effective symbioses than
rhizobia of the "cowpea" (V. unguiculata) miscellany. USDA257 nodulated an exact
subset (79 genera) of the NGR234 hosts (112 genera). If only one of the bacteria
formed effective, nitrogen-fixing nodules it was usually NGR234. The only
exceptions were with Apios americana, Glycine max, and G. soja. Few correlations
can be drawn between Nod-factor substituents and the ability to nodulate specific
legumes. Relationships between the ability to nodulate and the origin of the host
were not apparent. As both P. andersonii and NGR234 originate from
Indonesia/Malaysia/Papua New Guinea, and NGR234's preferred hosts
(Desmodiinae/Phaseoleae) are largely Asian, we suggest that broad host range
originated in Southeast Asia and spread outward.
PMID- 10188271
TI - Cloning and characterization of an esophageal-gland-specific chorismate mutase
from the phytoparasitic nematode Meloidogyne javanica.
AB - Root-knot nematodes are obligate plant parasites that alter plant cell growth and
development by inducing the formation of giant feeder cells. It is thought that
nematodes inject secretions from their esophageal glands into plant cells while
feeding, and that these secretions cause giant cell formation. To elucidate the
mechanisms underlying the formation of giant cells, a strategy was developed to
clone esophageal gland genes from the root-knot nematode Meloidogyne javanica.
One clone, shown to be expressed in the nematode's esophageal gland, codes for a
potentially secreted chorismate mutase (CM). CM is a key branch-point regulatory
enzyme in the shikimate pathway and converts chorismate to prephenate, a
precursor of phenylalanine and tyrosine. The shikimate pathway is not found in
animals, but in plants, where it produces aromatic amino acids and derivative
compounds that play critical roles in growth and defense. Therefore, we
hypothesize that this CM is involved in allowing nematodes to parasitize plants.
PMID- 10188272
TI - The 5' noncoding region of grapevine chrome mosaic nepovirus RNA-2 triggers a
necrotic response on three Nicotiana spp.
AB - The 5' noncoding region (NCR) of grapevine chrome mosaic nepovirus (GCMV) was
cloned in a viral vector derived from potato virus X (PVX). The recombinant virus
obtained was inoculated to Nicotiana benthamiana, N. clevelandii, and N. tabacum
plants. Infected plants developed necrotic symptoms in place of the vein clearing
and mosaic typically observed after inoculation with PVX. Northern (RNA) blot
analysis showed that the replication of PVX was not specifically altered by the
presence of the GCMV 5' NCR. Inoculation of recombinant PVX harboring deleted
forms of the GCMV 5' NCR showed that the three stem-loop structures at the 3' end
of the 5' NCR (nucleotides 153 to 206) are dispensable for the induction of
necrosis. Further deletion analysis indicated that neither the 5'-most 70
nucleotides of the 5' NCR nor the downstream region (nucleotides 71 to 217) alone
is able to induce the necrotic symptoms. In the presence of both the sequence
encoding the GCMV coat protein and the GCMV 3' NCR, the GCMV 5' NCR failed to
induce necrosis in the PVX background. The mechanisms by which the expression of
the 5' NCR might modify PVX symptoms are discussed.
PMID- 10188273
TI - In situ detection of Escherichia coli cells containing ColE1-related plasmids by
hybridization to regulatory RNA II.
AB - A method is described for the in situ detection of individual whole fixed cells
of Escherichia coli containing ColE1-related plasmids. It makes use of
fluorescence in situ hybridization (FISH) and the regulatory RNA II as a target
molecule for both, Cy3- and HRP-labeled olinucleotide probes. Various methods for
signal amplification were compared. Probes targeting the regulatory RNA I did not
result in the in situ detection of plasmid-bearing cells.
PMID- 10188274
TI - Determination of the nucleotide sequence of the 23S ribosomal RNA and flanking
spacers of an Enterococcus faecium strain, reveals insertion-deletion events in
the ribosomal spacer 1 of enterococci.
AB - The usefulness of 16S-23S (ITS1) and 23S-5S (ITS2) ribosomal spacer nucleotide
sequence determination, as a complementary approach to the biochemical tests
traditionally used for enterococcal species identification, is shown by its
application to the identification of a strain, E27, isolated from a natural
bacteria mixture used for cheese production. Using combined approaches we showed,
unambiguously, that strain E27 belongs to the Enterococcus faecium species.
However, its ITS1 region has an interesting peculiarity. In our previous study of
ITS1s from various enterococcal species (NAIMI et al., 1997, Microbiology 143,
823-834), the ITS1s of the two E. faecium strains studied, were found to contain
an additional 115-nt long stem-loop structure as compared to the ITS1s of other
enterococci, only one out of the 3 ITS1s of E. hirae ATCC 9790, was found to
contain a similar 107-nt long stem-loop structure. The ITS1 of strain E27 is 100%
identical to that of E. faecium ATCC 19434T, except that the 115-nt additional
fragment is absent. This strongly suggests the existence of lateral DNA transfer
or DNA recombination events at a hot spot position of the ITS1s from E. faecium
and E. hirae. Small and large ITS1 nucleotide sequence determination for strain
E27 generalized the notion of two kinds of ITSs in enterococci: one with a
tRNA(Ala) gene, one without tRNA gene. To complete strain E27 characterization,
its 23S rRNA sequence was established. This is the first complete 23S rRNA
nucleotide sequence determined for an enterococcal species.
PMID- 10188275
TI - Characterization of the koala biovar of Chlamydia pneumoniae at four gene loci-
ompAVD4, ompB, 16S rRNA, groESL spacer region.
AB - Koalas are infected with two species of Chlamydia, C. pecorum and C. pneumoniae.
While it is known that significant genetic diversity occurs in the C. pecorum
strains infecting koalas, very little is known about the C. pneumoniae strains
that infect this host. In the current study, 10 isolates of koala C. pneumoniae
were analysed at four gene loci and found to be different to both the human and
horse C. pneumoniae strains at all loci (biovar differences ranging from 0.3% at
groESL up to 9.0% at ompAVD4). All koala biovar isolates studied were found to be
100% identical at ompAVD4 (all 10 isolates) and at ompB (all three isolates)
gene. This lack of allelic polymorphisms at ompAVD4 has now been observed for
koala C. pneumoniae, human C. pneumoniae, guinea pig inclusion conjuctivitis C.
psittaci and feline conjuctivitis C. psittaci and may be correlated to a lack of
antibody response to the chlamydial major outer membrane protein (MOMP) in these
same strain/host combinations. This study also provides the first documented case
of natural C. pneumoniae infection causing a severe and extended respiratory
episode in a captive koala population. This captive episode is in contrast to
most free-range observations in which koala C. pneumoniae is rarely documented as
causing respiratory, ocular or urogenital tract disease.
PMID- 10188276
TI - Phylogeny and diversity of Achromatium oxaliferum.
AB - Achromatium oxaliferum was first described in 1893 by Schewiakoff as an unusually
large bacterium living in freshwater sediments. Up to now no pure culture is
available. Physical enrichments of achromatia collected from the acidic Lake
Fuchskuhle, which houses a peculiar, smaller variety, and the neutral Lake
Stechlin were investigated by the cultivation-independent rRNA approach. PCR in
combination with cloning and sequencing was used for the retrieval of 24 partial
and 4 nearly full-length 16S rRNA sequences that formed two distinct phylogenetic
clusters. Fluorescence-in-situ-hybridization (FISH) with four 16S rRNA-targeted
oligonucleotide probes unambiguously assigned the different sequences to either
regular, large A. oxaliferum cells or to the smaller Lake Fuchskuhle population,
tentatively named "A. minus". The two Achromatium sp. 16S rRNA sequence clusters
form a stable deep branch in the gamma subclass of the class Proteobacteria. The
closest cultivated relatives are Chromatium vinosum, Rhabdochromatium marinum and
Ectothiorhodospira halophila with 16S rRNA similarities of 86.2 to 90.5%.
Profound differences in the population structure of achromatia were revealed in
the two lakes by FISH. In one sample from Lake Stechlin three genotypes could be
visualized, and 49% of the cells were assigned to A. oxaliferum clone AST01, 28%
to Achromatium sp. genotype AFK192/AFK433 and 23% to Achromatium sp. genotype
AFK192/AST433. In contrast, a morphologically and phylogenetically homogeneous
population of "A. minus". was present in Lake Fuchskuhle.
PMID- 10188277
TI - Phylogenetic relationships of a large marine Beggiatoa.
AB - Based upon 16S rRNA sequence and phenotypic similarities, a large, uncultured
Beggiatoa sp. from the Bay of Concepcion (Chile), is very closely related to the
Chilean Thioploca species Thioploca araucae., whose filaments grow as sheathed
bundles. The formation of sheathed filament bundles, the key character to
distinguish the genus Thioploca from Beggiatoa, places closely related
filamentous sulfur-oxidizing bacteria into two different genera, incongruent with
16S rRNA-defined clades.
PMID- 10188278
TI - Taxonomic study of bacteria isolated from natural mineral waters: proposal of
Pseudomonas jessenii sp. nov. and Pseudomonas mandelii sp. nov.
AB - The taxonomic position of 23 strains isolated from mineral waters and previously
grouped in the authentic pseudomonads on the basis of a phenotypic analysis
(cluster IX, subclusters XIIIa and XIIIc of VERHILLE, S., ELOMARI, M., COROLER,
L., IZARD, D., LECLERC, H. (Syst. Appl. Microbiol, 20, 137-149, 1997) has been
genotypically further studied in the present work. On the basis of hybridization
results, these strains were gathered into two new genomic groups for which we
propose the names of Pseudomonas jessenii sp. nov. (Type strain CIP 105274) and
Pseudomonas mandelii sp. nov. (Type strain CIP 105273). Deoxyribonucleic acid
relatedness levels showed homologies ranging from 78 to 100% for Pseudomonas
jessenii and from 77 to 100% for Pseudomonas mandelii. Furthermore, hybrization
rates with 66 representative well characterized species or only partially
characterized species of the genus Pseudomonas were below 53%, with delta Tm
values of 7 degrees C and more. The mol% G + C content ranged from 57 to 58. The
two new species presented basic morphological characteristics common to all
pseudomonads. Various phenotypic features, such as denitrification, growth at 4
degrees C or 41 degrees C, trigonelline assimilation, alpha-L-glutamyl-L
histidine arylarmidase activity, growth on benzoate and meso-tartrate were found
to differentiate Pseudomonas jessenii from Pseudomonas mandelii and from other
Pseudomonas species. Pseudomonas jessenii encompassed a total of 9 strains from
both phenotypic groups IX and XIIIa. Pseudomonas mandelii clustered a total of 13
strains from both phenotypic groups IX and XIIIc. Their clinical significance is
unknown. The 16S rDNA of each type strain was sequenced and compared with the
known sequences of the representative strains of the genus Pseudomonas. A
phylogenetic tree was constructed to determine the intrageneric relationships
within the genus Pseudomonas.
PMID- 10188279
TI - Phylogenetic analysis of proteolytic Acinetobacter strains based on the sequence
of genes encoding aminoglycoside 6'-N-acetyltransferases.
AB - The sequence of seven aac(6')-I genes encoding aminoglycoside 6'-N
acetyltransferases from proteolytic Acinetobacter strains including genomic
species 14, 15, 16, and 17 and from ungrouped proteolytic strains 631, 640, and
BM2722 was determined. Pulsed-field gel electrophoresis of genomic DNA of these
strains and of Acinetobacter sp. 6 CIP A165 digested with SfiI followed by
hybridization with rRNA and aac(6')-I specific probes indicated that these genes
were located in the chromosome. Phylogenetic analysis of the genes indicated that
aac(6')-I of A. baumannii, Acinetobacter ungrouped strain 631, and Acinetobacter
sp. 16 formed a cluster (91.5 to 92.3% identity) whereas aac(6')-I of
Acinetobacter sp. 15, sp. 17, and Acinetobacter ungrouped strain BM2722 formed
another cluster (90.7 to 94.6% identity). A third cluster was constituted by A.
haemolyticus and Acinetobacter sp. 6 (83.6% identity). The phylogeny drawn from
aac(6')-I sequences was consistent with that based on DNA-DNA hybridization and
phenotype comparison. The aac(6')-I genes were all species specific except for
aac(6')-Ih located in a 13.7-kb non conjugative plasmid from A. baumannii BM2686.
We conclude that aac(6')-I genes may be suitable for identification at the
species level and for analysis of the phylogenetic relationships of
Acinetobacter.
PMID- 10188280
TI - Physiological and phylogenetic diversity of bacteria growing on resin acids.
AB - Resin acids are tricyclic diterpenes which are synthesized by trees and are a
major cause of toxicity of pulp mill effluents. Bacterial strains isolated from
three different sources and which grow on resin acids were physiologically
characterized. Eleven strains, representating distinct groups, were further
characterized physiologically and phylogenetically. The isolates had distinct
specificities for use, as growth substrates, of the different resin acids tested.
The isolates also used fatty acids but were generally limited in use of other
diverse substrates tested. According to their 16S rDNA sequences, the
representative isolates are related to members of the genera, Sphingomonas,
Zoogloea, Ralstonia, Burkholderia, Pseudomonas and Mycobacterium. Analysis of
whole-cell fatty acid profiles generally supported those phylogenetic
relationships. However, most of the isolated did not have high similarities to
reference strains in the Microbial Identification System database of fatty acid
profiles or in the Biolog database of substrate oxidation patterns. Described
species of Sphingomonas, Zoolgoea, Burkholderia Pseudomonas, most closely related
to the isolates we characterized, failed to grow on, or degrade, resin acids. We
propose recognition of Zoogloea resiniphila sp. nov., Pseudomonas vancouverensis
sp. nov., P. abietaniphila sp. nov. and P. multiresinivorans sp. nov.
PMID- 10188281
TI - Non-universal usage of the leucine CUG codon and the molecular phylogeny of the
genus Candida.
AB - CUG, a universal leucine codon, was reported to be read as serine in 10 species
of the genus Candida. We used an in vitro cell-free translation system to
identify the amino acid assignment of codon CUG in 78 species and 7 varieties of
galactose-lacking Candida species equipped with Q9 as the major ubiquinone. Of
these, only 11 species used codon CUG as a leucine codon. The remaining species
decoded CUG as serine. Their small subunit ribosomal DNA sequences were also
determined and analyzed using both Neighbor-Joining and Maximum Likelihood
methods. The species decoding CUG as serine and leucine formed distinct clusters
on both molecular phylogenetic trees. Our result suggests that non-universal
decoding is not a rare event, and that it is widely distributed in the genus
Candida.
PMID- 10188282
TI - A polyphasic study on the taxonomic position of industrial sour dough yeasts.
AB - The sour dough bread making process is extensively used to produce wholesome
palatable rye bread. The process is traditionally done using a back-slopping
procedure. Traditional sour doughs in Finland comprise of lactic acid bacteria
and yeasts. The yeasts present in these doughs have been enriched in the doughs
due to their metabolic activities, e.g. acid tolerance. We characterized the
yeasts in five major sour bread bakeries in Finland. We found that most of the
commercial sour doughs contained yeasts which were similar to Candida milleri on
the basis of 18S rDNA and EF-3 PCR-RFLP patterns and metabolic activities. Some
of the bakery yeasts exhibited extensive karyotype polymorphism. The minimum
growth temperature was 8 degrees C for C. milleri and also for most of sour dough
yeasts.
PMID- 10188283
TI - Polyphasic taxonomy of a novel yeast isolated from antarctic environment;
description of Cryptococcus victoriae sp. nov.
AB - In 1992 some samples of mosses, lichens and soils were collected from Botany Bay,
Southern Victoria Land (77 degrees 01' S 162 degrees 32' E) and, as a result of a
routine screening programme some yeasts were isolated. One of them, designated as
strain G5, showed marked differences when compared to other antarctic yeasts.
According to morphological and physiological characteristics, we were able to
identify the strain G5 as a yeast belonging to the genus Cryptococcus. Some
characteristics of this genus are the growth response to myo-inositol, celobiose,
raffinose and D-glucuronate, no-fermentation, the absence of mycelium and
pseudomycelium, asexual reproduction, Diazolium blue B test (DBB) and urea
hydrolisis positive and the growth without vitamines. This strain (G5) formed
cream colonies of slimy appearance with cells of 3 x 2 microns in size, that grew
between 4 degrees C and 20 degrees C. The G + C content of strain G5 was 50.3
mol%. The molecular characterization by whole-cell proteins and RFLP analysis of
the 5.8S rRNA gene and the two ribosomal internal transcribed spacers (5.85-ITS
region), revealed that this strain was different from other antarctic species of
this genus. The phylogenetic tree deduced from the 5.8S rRNA gene sequence showed
the strain G5 as a member of the genus Cryptococcus, clearly separated from other
basidiomycetous yeasts. On the basis of the physiological, genotypical and
phylogenetical data, the new isolate G5 was described as Cryptococcus victoriae,
sp. nov., with the type strain G5 (= CECT 11114).
PMID- 10188285
TI - Evaluation of methods for recognising strains of the Bacillus cereus group with
food poisoning potential among industrial and environmental contaminants.
AB - Toxin production, biochemical properties and ribotypes of Bacillus cereus group
(B. cereus, B. thuringiensis, B. mycoides) strains originating from industrial
and environmental sources (n = 64), from food poisoning incidents (n = 22) and
from reference sources (n = 7) were analysed. Forty ribotypes were found among
the 93 strains. Eleven strains from food poisoning incidents produced emetic
(mitochondrio) toxin, as determined by the boar spermatozoa toxicity test. These
strains possessed closely similar ribotypes which were rare among strains of
other origins. Sperm toxin producing (cereulide positive) strains did not
hydrolyse starch and did not produce haemolysin BL, as determined by the reverse
passive latex agglutination test. Sixteen different ribotypes were found among B.
cereus strains from board machines (n = 16) and from packaging board (n = 16),
indicating many different sources of B. cereus contamination in board mills.
Strains originating from packaging board had predominantly different ribotypes
from those of dairy and dairy product originating strains. Nine (53%) out of 17
strains from a single dairy process shared the same ribotype whereas strains from
milk and milk products from different dairies had different ribotypes indicating
that B. cereus group populations were dairy specific. Twenty-two percent of
strains isolated from the paperboard industry on non-selective medium were
lecithinase negative, including enterotoxin producing strains. This stresses the
importance of other detection methods not based on a positive lecithinase
reaction.
PMID- 10188284
TI - Importance of Xanthobacter autotrophicus in toluene biodegradation within a
contaminated stream.
AB - Toluene-degrading strains T101 and T102 were isolated from rock surface biomass
in a toluene-contaminated freshwater stream. These organisms were present at a
density of 5.5 x 10(6) cells/g of rock surface biomass. Both are aerobic, rod
shaped, Gram-negative, non-motile, catalase-positive, oxidase-positive, with
yellow pigments, and can grow on benzene. Phylogenetic analyses show that strains
T101 and T102 have 16S rDNA sequences identical to Xanthobacter autotrophicus.
Fatty acid analyses indicate that they are different strains of the same species
Xanthobacter autotrophicus, and that they have high levels of cis-11-octadecenoic
acid and cis-9-hexadecenoic acid; 3-hydroxyhexadecanoic acid is the major hydroxy
fatty acid present. Strains T101 and T102 had maximal velocities (Vmax) for
toluene biodegradation of 3.8 +/- 0.5 and 28.3 +/- 2.2 mumoles toluene/mgprotein
hr, and half-saturation constants (Ks) of 0.8 +/- 0.5 and 11.5 +/- 2.4 microM,
respectively. Strain T102 has a higher capacity than strain T101 to degrade
toluene, and kinetic calculations suggest that strain T102 may be a major
contributor to toluene biodegradation in the stream.
PMID- 10188286
TI - Characterization of Saccharomyces cerevisiae CBS 7764 isolated from rainbow trout
intestine.
AB - A wild-type Saccharomyces cerevisiae, strain CBS 7764, isolated from the
intestine of rainbow trout, was analyzed with respect to general growth
parameters and global protein expression. Characterization of this strain was of
interest since previous data show non-typical S. cerevisiae cell surface
properties and because data suggest a probiotic potential of CBS 7764. The heat
production rate (dQ/dt), monitored by microcalorimetry, showed that the typical
growth phases resulting from diauxic growth on glucose were present in the fish
isolate. However, CBS 7764 differentiated from a reference strain by becoming
limited in the respiratory phase as demonstrated by a plateau in the dQ/dt
signal. The global protein expression, as studied by two-dimensional gel
electrophoresis (2D-PAGE), revealed a large degree of resemblance of the fish
isolate to the reference strain, however, also clear qualitative and quantitative
expression differences were detected; e.g. 14% of the proteins differed in
expression level by a factor of at least 2. In addition, the fish isolate
expressed 12 unique proteins. The heat shock proteins, which for other organisms
have been identified as important in mucosal colonization, were generally
expressed to a higher level in CBS 7764.
PMID- 10188287
TI - [Plastic surgery, this is too: 176 French humanitarian missions].
PMID- 10188288
TI - [Humanitarian plastic surgery].
PMID- 10188290
TI - [Humanitarian plastic surgery. Personal experience and reflections].
AB - After analysing their concept of humanitarian plastic surgery, the authors
present their personal experience which started in the 1970s, concerning two
aspects: in the field (Burkina-Faso, Mali, Niger) and in Geneva, Switzerland,
where the more difficult cases are operated. They illustrate their approach by a
clinical case of sequelae of noma. They analyse the problems and/or questions
raised by humanitarian plastic surgery: sufficient training, choice of surgical
techniques, postoperative follow-up, assessment of the results obtained, possible
innovations.
PMID- 10188289
TI - [What are the objectives of a humanitarian reconstructive plastic surgery
mission?].
AB - What is the place of plastic and reconstructive surgery within the field of
general surgery in developing countries? A limited personal experience (15
missions, 220 operated patients), and a more extensive experience of colleagues
working in the field for several years, constitute the starting point for
discussion. General surgery represented 80% of all surgical activity in the
1970s, but has progressively become more specialized. Analysis of the type of
operations shows that the most frequent techniques are simple procedures (skin
grafts, local autoplasties). "Basic" plastic surgery corresponds to local
possibilities and the population's real needs. The authors describe the demands
usually encountered during their missions (Africa, South East Asia). They
emphasize the long-term involvement of the same team, at the same site, with the
same program to pass on knowledge and, for the surgeon, to experience the
richness of another world.
PMID- 10188291
TI - [Plastic surgery training missions in developing countries. A 10-year experience
at missions in Mali].
AB - Humanitarian plastic surgery missions are often a substitute, as plastic surgery
training missions are essential for the development of plastic surgery in
developing countries. This training must be progressive and adapted to the
country's needs. Several simple plastic surgery techniques are sufficient to
treat a large number of patients: split-skin grafts, full-thickness skin grafts,
Z-plasties, latissimus dorsi myocutaneous pedicle flap.
PMID- 10188292
TI - [Surgery of labio-maxillo-palatal clefts during humanitarian mission in the
Philippines].
AB - After describing the Philippines and the Comite de Soutien Enfance Philippines, a
humanitarian association with a three-fold objective: to build, to educate and to
treat, the authors present the organization and practical conduct of their
missions abroad which have enabled them to treat almost 400 patients with cleft
lip and palate between the ages of 3 months and 46 years.
PMID- 10188293
TI - [Leprosy, an "exemplary" humanitarian disease?].
AB - Leprosy still remains a dreaded disease despite the possibilities of permanent
cure, the efficacy of surgical corrections, and its forthcoming disappearance.
The authors conducted several surgical missions in Benin-Africa--over 4 years and
report an interesting rate of control in the survey of patients as the results of
their procedures were reviewed in 84% of them. Leprosy represents the perfect
example of the difficulties of any humanitarian involvement with apparent
contradictions between the aims of the medical wishes and the presence of a
dreaded symbol that--fortunately or not--allow the existence of the many
associations involved in the fight against leprosy.
PMID- 10188294
TI - [Burn sequelae in developing countries].
AB - Based on their experience in the reconstruction of burn sequelae acquired over
the last decade in India and Africa, the authors try to define a number of
elements applicable to every case and in every country: the importance of
preparation of missions in the foreign country and in France, concerning material
and all team personnel; the particular conditions of anaesthesia-intensive care;
surgical criteria of efficacy, rapidity, simplicity and reproducibility. Full
thickness skin grafts and reliable local or regional flaps are the preferred
techniques. The authors consider that there is no place for expansion prostheses
and microsurgical free flaps in this setting.
PMID- 10188295
TI - [Humanitarian surgery of the hand. Our experience in Vietnam].
AB - After a general presentation of the geographical and social aspects of Vietnam,
the authors describe the conditions of their surgical work during short time
humanitarian hand surgery missions. These missions, lasting 7 to 10 days are
dedicated to the care of children, and a half-day of teaching for Vietnamese
corresponding surgeons. The technical and material limits, the constraints for
the patients to travel to the hospital, to pay for care and the difficulties of
follow-up, require the selection of patients in whom the disease can be treated
in a single stage procedure. Three types of diseases were treated: congenital
anomalies, post-burn and post-trauma sequelae. Typical cases of these diseases
are described and shown. Due to the absence of hand rehabilitation,
reconstructive tendon surgery is inadvisable to avoid disappointing poor results
and discredit this part of hand surgery. For reason of complexity and
unreliability of electromyographic examination, brachial plexus injuries cannot
be treated, except the simplest cases needing one or two tendon transfers.
Concerning skin coverage and reconstructive surgery, our experience has shown
that pedicled local and locoregional flaps, and even microsurgical transfers are
adapted and reliable techniques due to the imperative of single stage procedure.
The education and teaching of young surgeons in European teams and regular
relation-ships with corresponding surgeons from developing countries are
certainly the best way to promote humanitarian hand surgery.
PMID- 10188296
TI - [Humanitarian plastic surgery missions. Actions and reflections].
AB - After recalling the various possible objectives of humanitarian missions in
underprivileged countries, the authors describe the context of their plastic
surgery missions, each lasting two to three weeks, with the support of
Interplast. These missions have been conducted in India, Pakistan, Thailand,
Vietnam and Afghanistan. The organization is now classical: on site supply of
anaesthetic and all disposable material, 50 to 100 operations over a fortnight in
a local hospital. The diseases most frequently observed were cleft lip and palate
and post-burn skin retractions. The authors emphasize the fact that the mission
director must be an experienced surgeon in order to select the most reliable and
the simplest procedure. They analyse the meaning of their commitment and the way
in which this humanitarian action is perceived by the recipient country.
PMID- 10188297
TI - [Contribution of computers in reconstructive surgery missions in Third World
countries].
AB - The authors analyse the possible contribution of computers to the management of
patients operated as part of humanitarian reconstructive surgery missions. There
are many advantages: better preparation of missions, better evaluation of follow
up, possibility of exchange of files by Internet, or even remote medical
assistance.
PMID- 10188298
TI - [Falciform anemia and Plasmodium falciparum malaria: a threat to flap survival?].
AB - Plasmodium falciparum malaria, a parasitic disease, and sickle cell anemia, a
hereditary disease, are two diseases affecting erythrocyte cycle, occurring with
a high prevalence in tropical Africa. They may induce microthrombosis inducing
vaso-occlusion, organ dysfunction and flap necrosis. During the acute phase of
Plasmodium falciparum malaria, destruction of parasitized and healthy
erythrocytes, release of parasite and erythrocyte material into the circulation,
and secondary host reaction occur. Plasmodium falciparum infected erythrocytes
also sequester in the microcirculation of vital organs and may interfere with
microcirculatory flow in the flap during the postoperative period. The lower legs
of homozygous sickle cell anemia patients are areas of marginal vascularity where
minor abrasions become foci of inflammation. Inflammation results in decreased
local oxygen tension, sickling of erythrocytes, increased blood viscosity and
thrombosis with consequent ischemia, tissue breakdown and leg ulcer. Tissue
transfer has become the procedure of choice for reconstruction of the lower third
of the leg although flaps may become necrotic. The aim of this study is to
analyse circumstances predisposing to surgical complications and to define
preventive and therapeutic measures. A review of the literature will describe the
current research and the new perspectives to treat sickle cell anemia, for
example hydroxyurea and vasoactive substances (pentoxifylline, naftidrofuryl,
buflomedil).
PMID- 10188299
TI - [The forehead cutaneo-musculo-aponeurotic unit and aging of the forehead. Anatomo
physiological considerations and surgical implications].
AB - The occipitofrontalis muscle, as it is described in classical anatomy text books,
does not exist. The epicranial aponeurosis or galea aponeurotica receives the
occipitalis muscle on its deep surface and the frontalis muscle on its
superficial surface. The frontalis muscle plays a fundamental role not only in
forehead expression, but also in the support and elevation of the eyelids. This
revised and corrected anatomy gives rise to the concept of the forehead
cutaneomusculoaponeurotic unit, composed of skin, galea and frontalis muscle
(forehead CMAU), resulting in a new forehead facelift which corrects forehead
ageing, essentially related to recession of the forehead and relaxation of the
galea.
PMID- 10188300
TI - [Apropos of "Esthetic reconstruction of upper hemilip according to the Abbe
technique modified by Burget"].
PMID- 10188301
TI - Role of audiologists in vestibular and balance rehabilitation: position
statement, guidelines, and technical report. ASHA Ad Hoc Committee on Vestibular
Rehabilitation.
PMID- 10188302
TI - Competencies in auditory evoked potential measurement and clinical applications:
guidelines. ASHA Ad Hoc Committee on Auditory Evoked Potentials.
PMID- 10188304
TI - Learning disabilities: use of paraprofessionals. National Joint Committee on
Learning Disabilities.
PMID- 10188303
TI - Terminology pertaining to fluency and fluency disorders: guidelines. ASHA Special
Interest Division 4: Fluency and Fluency Disorders.
PMID- 10188305
TI - Reference list. Position statements, guidelines, and other relevant papers.
PMID- 10188306
TI - [Benefits and limitations of mass screening. The natural history of breast
cancer].
AB - Most mortalities caused by breast cancers are due to metastases. A breast cancer
gives rise to lymphatic spread, which is at the origin of nodal involvement, and
to distant dissemination, usually through the bloodstream. Nodal involvement,
which generally occurs before metastatic dissemination, appears not to be the
cause of the dissemination but rather an index of the likelihood of a tumor to
metastasize. This likelihood is influenced by the histological grade and the
growth rate of the tumor. Despite the variations in biological characteristics of
breast tumors and the likelihood of metastatic dissemination, the existence of a
relationship between tumor size and the probability of metastatic dissemination
enables the calculation of how many disseminations could be avoided through early
diagnosis and thus the gain in human life that screening could hope to achieve.
However, in reality, the effective gain is lesser because the rate of
participation is lower than 100% and the existence of false negatives (undetected
cancers) reduces the number of detected cancers. Furthermore, a high rate of
false positives increases the anxiety of women because they provoke unnecessary
examinations. Screening is worthwhile only if the increase in human life
outweighs the economic and social costs (anxiety, going to appointments) that it
may produce. It is therefore necessary to improve the benefits (fewer false
negatives) and to decrease the social and psychological costs (fewer false
positives). This can be done by the implementation of rigorous quality assurance,
systematic training of health care personnel, a follow-up of women who have been
screened, and an annual assessment of screening results. Screening in France
since 1994 has shown a marked improvement since the implementation of guidelines
prepared by the national screening committee which emphasize the need for quality
control and ongoing training of staff. However, the results vary greatly from one
county to another and are often below European standards, although some regions
in France are close to achieving these. This shows that the system of screening
in France, despite its organization involving many private and public radiology
departments, can give results equal to those in countries in which screening is
performed by a small number of specialized units. The French system requires
regional structures of orientation and evaluation. To be effective, these
structures must be guided by written legislation and regulations, otherwise they
will be unable to overcome the difficulties currently faced by the implementation
of mass screening.
PMID- 10188307
TI - [History of mammography].
AB - The History of mammography began in 1913, when a Berliner surgeon, A. Salomon
realized a roentgeno-histological study on 3,000 mastectomies. This work is the
basis of mammography. Until 1938, few articles were published but were of little
help to mammography. From 1947 to 1970, the second period brought the results of
roentgenologic and clinical correlation. R. Leborgne was the first accountable
for the wide development of this method. Since 1951, many American and European
radiologists brought their contribution. Ch. Gros is the best known. He gave this
technique an acknowledgment throughout the world for the diagnosis of breast
diseases. Since 1970, the third period emphasizes the value of mammography as a
technique for detection of breast cancer. Some "Screening working groups" are
being set up. The problem is mainly economical.
PMID- 10188308
TI - [Epidemiology of breast cancer].
AB - Breast cancer is the predominant cancer among women in France, accounting for
about 32% of all new cases. Increasing incidence rates are reported by the
regional registries, while the national mortality rates seem to reach a plateau
particularly in the women under 65 years old. During the last 20 years the
survival of patients with positive nodes has been increased. Nulliparity and
increasing age at first birth are well established risk factors as well as age at
menarche and age at menopause (OR approximately equal to 2). The role of other
risk factors such as hormone replacement therapy, oral contraception, lactation
remain controversial (OR approximately equal to 1-1.5). Total calories
consumption, obesity after menopause, and alcohol are possible risk factors (OR
approximately equal to 2-3). Previous irradiation of thorax, proliferative benign
mastopathy are increasing the risk of breast cancer (OR approximately equal to 3
5). Consumption of fruits and vegetables, as well as physical exercise could
decrease the risk (OR approximately equal to 0.6). There is a strong heredity
component for about 10-15% of the cases. Approximately in half of these cases a
mutated gene (Brca1, Brca2 ...) have been identified.
PMID- 10188309
TI - [Breast cancer screening: ethical problems. The Strasbourg experiment.
Deontological issues raised by breast cancer screening: quality assurance and
accreditation of structures].
AB - Cancer of the breast is so widespread that it has become a genuine problem of
public health, with around one woman in twelve developing it in her lifetime.
Mass breast-cancer screening campaigns began some 30 years, first in the United
States and then in Sweden. Results showed a lowering of the breast-cancer-related
death-rate. French doctors experienced considerable difficulties in changing over
from an individually-focused organization to the kind of public healthcare
service that exists in Nordic and Anglo-saxon countries. However, the first
departmental-level breast-cancer screening program, launched in Strasbourg,
France, in 1989 proved successful inasmuch as it obtained the involvement of the
vast majority of radiologists and general practitioners. Results of the campaign
were broadly in line with those obtained elsewhere in Europe. It is only possible
to bring this sort of campaign into wider use through intensive groundwork and by
providing suitable training for general practitioners, radiologists and
gynecologists alike.
PMID- 10188310
TI - [Prospective view concerning organization of breast cancer screening in France].
AB - Development of an organized cancer screening is today an essential axis of Public
Health. Successive sequences are the test, the experience and the generalization.
There are three principles for this generalization: 1. transparence with a
specific act coding; 2. selectivity to assure the quality at each stage of this
process; 3. responsibility on both professionals and policy holder levels. A such
organization can only find its reasons in: 1. a legislative text who sets a very
strict frame in accordance with regulations with a specific list and therefore
differed for the act itself; 2. professionals and structures approved for
organized screening acts, covered at 100%. The regional level will certainly be
at the center of this system. Three authorities are marked out for playing
significant role: the Regional Direction of Sanitary and Social Action, the
Regional Union of Sickness Insurance Funds and the Regional Union of Liberal
Physicians. If those measures and this organization might improve the quality of
screening acts, they would be for the major part ineffective if they don't allow
to get back to women who today escape, for the major part, this prevention
process. They are essentially persons aged of 55 years old and over and the most
deprived public. In this prospect, the general practitioner must play an
essential role in a same time to go back to those public and ease an open to a
dialogue around screening.
PMID- 10188311
TI - [Breast cancer screening. From the experimental phase to generalization].
PMID- 10188312
TI - [Organized breast cancer screening: experience at Bouches-du-Rhone].
PMID- 10188313
TI - [Breast cancer screening. Objectives of a professional structure].
PMID- 10188314
TI - [Breast cancer screening. Allocution].
PMID- 10188315
TI - [Definition and evaluation of therapeutic food for severely malnourished children
in situations of humanitarian emergencies].
AB - Nowadays, median case fatality rate of severely malnourished children treated in
hospitals is 23.5%, a rate which has not changed for the last 50 years. This is
probably related to the use of inappropriate or even unsafe treatment protocols.
This work aimed at reducing case fatality rates of severe malnutrition by
developing a treatment protocol and assessing its effectiveness during
humanitarian crises. A therapeutic food was designed from pathophysiologic
studies and its use adapted to therapeutic feeding centres. This food (F100)
contains 100 Kcal/100 ml, with 10% of its energy derived from proteins; it has a
low sodium and iron content but is fortified with vitamins and minerals. It can
be prepared either at the treatment centre or at an industrial level. Industrial
production, which started in 1993 reached 1,500 MT in 1997. In refugee camps,
F100 was used according to a strict protocol adapted to local conditions. Intakes
started at 100 Kcal/kg/day and reached 200 kcal/kg/day once appetite was
restored. A model to assess the risk of death according to weight, height and
oedema was developed. First results show that mortality was often below 5%.
Hence, it is possible to standardise and evaluate a nutritional treatment in such
unfavourable conditions as a refugee camp. Standardised use of F100 can markedly
reduce mortality of severely malnourished children.
PMID- 10188316
TI - [Circannual rhythm of the risk of IgE-dependent sensitization to acari depending
on the birth date. Interpretation and practical consequences in prevention].
AB - The role of allergenic environment during the first weeks of life for the future
development of IgE-dependent allergy is well documented for cyclic allergens.
That is less evident for permanent antigens as house dust mites. The aim of this
work was to find a possible relation between the birth date and house dust mite
hypersensitivity to have a better prevention. The result of Rast d1 which show an
IgE-dependent allergy to Dermatophagoides pteronyssinus was correlated to the
month of birth of 5, 747 children and adolescents with a suspected allergic
respiratory disease. Possible bias induced by sex and personal/family history
were mathematically corrected. A correlation curve between the month of birth and
the frequency of positive Rast d1 was deduced. There is a circannual rhythm risk
for house dust mite allergy according to the month of birth. It draw a sinusoid
curve with a peak at 104 percent in october and a minimum at 96 percent in april.
These data were discussed. The minimum of risk was possibly due to better early
ecologic way of life for infants born during the spring. Preventive methods were
available against house dust mites. They could be organized for infants. We hope
that more pediatricians were concerned by primary prevention of house dust mite
allergy.
PMID- 10188317
TI - [Infection on foreign material: bacterial colonization of ureteral
endoprostheses].
AB - Infection on foreign body: bacterial colonization of ureteric stents. The most
frequent cause of the early removal of ureteric endoprostheses (double J) is
generally due to bacterial colonization. In order to prevent or to restrict the
prosthesis colonization, it is necessary to understand the major steps and the
factors influencing the colonization. This is the reason why we aimed to extract
the most relevant parameters influencing the bacterial colonization from the
observations made in vivo thanks to in vitro analyses. We have studied in vivo
the relationship between the bacterial colonization of the endoprostheses, the
urinary infections and the antibiotherapy. In vitro, we have defined the
conditions promoting the primary adhesion of the most frequently isolated
bacteria on endoprostheses. Surface properties of bacteria and materials have
been compared to:--the bacterial count of infected double J samples with respect
to bacterial species,--the bacterial count of the infected samples with respect
to pH and Ca2+, Mg2+ concentration. The results show a great variability of the
biomaterial surface properties which could be optimized, the fact that the
urinary medium acidification could lower the bacterial adhesion and the ambiguous
role of Ca2+ and Mg2+ ions which is discussed in this paper. In the case of in
vivo analyses, the conflicting results between leukocyturia and bacteriuria lead
to the detection of the bacterial colonization under antibiotic treatment. The
characterized urinary infection must warn the risk of pyelonephritis.
PMID- 10188318
TI - [Role of antineuraminidase antibodies in protection against influenza].
AB - For improving the anti-influenza vaccination efficacy, the choice of strains
carrying up dated neuraminidase antigen (NA) and the introduction of the optimal
amount of NA antigen in the vaccine are critical. Monoclonal antibodies prepared
against the neuraminidase N2 of A/Beijing/32/92 showed NA inhibition (NI) and
neutralized (Nt) the cells infection by influenza virus either at an early stage
(group 2 antibodies inhibit virus binding to cells) or at a late stage of
infection (group 1 antibodies inhibit virus release). The specificity of the
neutralization test is restricted to the homologous variant whereas the NI
specificity is much broader. When both group 1 and group 2 antibodies are tested
together, their neutralizing activity is significantly increased. The emergence
in 1997 of an avian strain H5N1 in humans influenza infections at Hong Kong
(Strain A/Hong-Kong/156/97) rose the threat of pandemic. The H5N1 strain carried
H5 HA which is not recognized by the human immune system, but N1 might be related
to other N1 antigens belonging to avian, swine and human strains. So we 1)
characterized the N1 antigen from H5N1 in comparison with other known antigens,
2) we looked for anti N1 (H5N1) antibodies in humans according to the age and the
vaccination status, 3) we checked the neutralizing activity of anti N1
antibodies. The N1 antigen (H5N1) appeared closely related to N1 from swine
strains: Sw/31 correlated itself to the pandemic spanish virus (1918-19), and
more recent swine isolates from 1982 and 1989. The anti N1 (H5N1) antibodies were
present in sera collected from 75+ years old persons and these N1 antibodies were
neutralizing H5N1 cells infection. Consequently, 75+ years old persons do not
represent a priority group for vaccination in the case of H5N1 pandemic
conditions.
PMID- 10188319
TI - [Anatomical repair in transposition of great vessels].
AB - Transposition of the great arteries (TGA) covers a wide range of anatomic
variants involving not only the origin of the great arteries, but the
intracardiac structures and the aortic arch. TGA can now benefit from complete
anatomic repair, namely switch operation, performed in simple forms during the
neonatal period. Accurate pre and intraoperative assessment must take into
account the main anatomic features: relationship between the aorta and the
pulmonary artery and coronary arteries distribution. Over the last sixteen years,
1,063 patients with TGA underwent anatomic repair in our institution. Among 728
patients with simple TGA, 92% were operated on within the first 2 weeks of life.
Among 335 patients with complex TGA, all had a large VSD and 154 had additional
anomalies. Among these 335 patients, 264 had one-stage complete repair and 71 had
two-stage repair, at the beginning of our experience. In complex forms the main
associated anomalies involved the ventricles (right ventricle hypoplasia (11),
malaligned VSD (90), restrictive VSD (3), multiple VSD (43), the atrioventricular
valves (straddling of the mitral or tricuspid valve (15), mitral valve anomalies
(cleft or tissue tag, 4) and the aortic arch (coarctation [88], interrupted
aortic arch (8)). The hospital mortality was 6.9% for simple TGA, 14.6% for
complex TGA. Main causes of early death were failure in coronary artery
relocation and pulmonary hypertensive crisis. Mean follow-up (95.5% of patients)
was 49 months. Overall 16-year survival was 87.9%, 91.5% for simple forms and
80.4% for complex forms. Anatomic repair is nowadays the treatment of choice for
TGA. Long-term results will depend on the evolution of the relocated coronary
arteries and of the neo-aortic valve.
PMID- 10188320
TI - Malaria deaths in Canadian travellers.
PMID- 10188321
TI - Transfusion-transmitted malaria in Canada.
PMID- 10188322
TI - Respiratory virus surveillance. FluWatch project.
PMID- 10188323
TI - [The New Year: it's a time of change].
PMID- 10188324
TI - [Vascular gene therapy--the choice of procedures as a function of strategies].
PMID- 10188325
TI - [The role of echocardiography in the first hours of a suspected or certain acute
myocardial infarct].
PMID- 10188326
TI - [Fibrinolysis in ischemic cardiopathy: the role of plasminogen activator
inhibitor 1].
PMID- 10188327
TI - [The antibiotic prophylaxis of endocarditis in the dental patient at risk].
PMID- 10188328
TI - [The genetic component of coronary risk--I].
PMID- 10188329
TI - The ranking of Italy's publications in the biomedical field: an objective
evaluation.
AB - To evaluate the scientific output of Italy compared to other countries in
clinical and basic research, the twelve top ranking journals according to the
impact factor in each group were considered. A total impact factor score of one
country was the sum of the impact factor of all articles attributed to a certain
country in all journals. Italy ranked sixth in clinical research but only ninth
in basic research. According to our analysis, the Italian scientific output in
the biomedical field is comparable to that of other countries. Further financial
analysis of the correlation between research funding and scientific output could
allow a more productive allocation of resources.
PMID- 10188331
TI - Minimally invasive direct coronary artery bypass and the limit between clinical
research and practice.
PMID- 10188330
TI - [The early angiographic follow-up of myocardial revascularization in a
minithoracotomy: the results of the first 100 consecutive cases].
AB - The use of the left internal thoracic artery anastomized to the left anterior
descending coronary artery via a small left thoracotomy to revascularize the
anterior wall of the left ventricle has gained wide acceptance since its
introduction into clinical practice a few years ago. A mandatory, postoperative
angiographic control was suggested in order to check the surgical results of this
new method of revascularization. We herein analyze the results of the in-hospital
angiographic control of a series of 100 consecutive patients who underwent
minimally invasive coronary artery bypass. In all 100 patients the thoracic
graft, the anastomosis and the target vessel were patent, with no anomalies in 90
subjects. In 4 patients, a sharp angulation of the thoracic artery in the last
third before the anastomosis to the native vessel was observed; in 3 subjects,
the arterial graft had been anastomized to a diseased tract of the target vessel
and in 3 cases a significant stenosis of the target vessel beyond the anastomosis
was documented; in 2 cases the persistence of a thoracic artery branch was
discovered. Since 1) neither in-hospital total occlusion of the thoracic graft to
the left anterior descending coronary artery via a small thoracotomy was
documented nor a significant incidence of major anomalies was observed; 2) the
anomalies documented seem to be clinically negligible and may regress in the
midterm postoperative period; 3) Doppler flow analysis is able to detect not only
the patency but also the presence of significant stenosis in the arterial graft;
the in-hospital angiographic control of this surgical technique should be limited
to patients with abnormal ultrasonic data or with reappearance of myocardial
ischemia in the anterior wall of the left ventricle, thus not reducing the
advantages in terms of speed and cost-control of this type of myocardial
revascularization.
PMID- 10188332
TI - A typical pattern of activation in the right atrium during paroxysmal atrial
fibrillation: the washing-machine phenomenon.
AB - Atrial fibrillation affects a large population of patients. The
electrophysiological mechanisms that initiate and maintain atrial fibrillation
may be multiple. Even if some studies exploring right atrial activation have been
recently published, data concerning atrial fibrillation activation patterns and
its mechanisms are still scarce and controversial. This study supplies
information on right atrial activation during atrial fibrillation. Twenty-four
patients with recurrent, drug-refractory, lone paroxysmal atrial fibrillation
underwent an extensive mapping of the right atrium. A pattern of organized atrial
fibrillation (type 1) was noted in the trabeculated right atrium and atrial roof,
characterized by discrete atrial electrograms, separated by an isoelectric
baseline, with a continuous switching between clockwise and counterclockwise
activation that we called washing-machine phenomenon. In the majority of
patients, recordings from the anterior and medial areas of the atrial septum,
showed fractionated electrograms consistent with a more disorganized activation
pattern. Atrial activation in the inferior septum and coronary sinus was rather
disorganized, neither synchronized with the activation sequence of the
trabeculated right atrium nor with that of the anterior septum. Furthermore, the
activation pattern showed fractionated electrograms and a variability of the
isoelectric baseline similar to that recorded in the septum. No significant
complications were reported during the procedure. In conclusion, mapping of the
right atrium during induced atrial fibrillation shows a very typical pattern of
activation in the trabeculated right atrium that we called the washing-machine
phenomenon. Whether this sequence of activation represents a bystander situation
or an active conditioning factor needs further investigations.
PMID- 10188333
TI - [Simvastatin and ischemia-reperfusion damage: its effects on apoptotic myocyte
death and on the endothelial expression of nitric-oxide synthetase in an
experimental model of the isolated rat heart].
AB - Recent studies have suggested that simvastatin may exert endothelial-protective
and anti-ischemic effects via nitric oxide (NO) mechanisms. The aim of this study
was to evaluate, in isolated working rat hearts, the effect of acute simvastatin
administration on endothelial and inducible NO-synthase (eNOS and iNOS) mRNA and
on myocytic apoptosis after ischemia-reperfusion. We used isolated working rat
hearts submitted to 15 min global, no-flow, normothermic ischemia and 180 min
reperfusion. To detect myocytic apoptosis we used DNA agarose gel electrophoresis
and Tunel technique; eNOS and iNOS expression were evaluated by multiplex reverse
transcriptase-polymerase chain reaction; glyceraldehyde-3-phosphate dehydrogenase
(G3PDH) was used as standard. The eNOS and iNOS mRNAs were expressed as
G3PDH/eNOS and G3PDH/iNOS densitometric ratio (BioRad Gel Doc 1000). Hearts were
divided into four groups: A) hearts excised and used as histological controls; B)
untreated hearts submitted to ischemia and reperfusion; C) actinomicin D-treated
(1.5 mg/kg) hearts, perfused with 25 microM simvastatin, subjected to ischemia
and reperfusion; D) hearts treated with simvastatin 25 microM and submitted to
ischemia and reperfusion. In Group B we evidenced a significant myocytic
apoptotic damage, reduced in groups C and D. In Group B an increase in G3PDH/eNOS
ratio vs Group A was detected; in Group D a reduction in G3PDH/eNOS ratio vs
Group B occurred; no significant changes were observed between groups C and D. As
for G3PDH/iNOS ratio, it was significantly increased in Group D with respect to
groups A and B. Our data suggest that simvastatin in acute may modulate NO
synthase mRNA expression (induction of eNOS mRNA by means of post-transcriptional
mechanisms and inhibition of iNOS postischemic overexpression) and reduce
myocytic apoptosis.
PMID- 10188334
TI - [A hyperhomocysteinemia study in a population with a familial factor for acute
myocardial infarct and sudden cardiac death at a young age].
AB - The alterations of the metabolism of methionine determining an accumulation of
homocysteine in blood (hyperhomocysteinemia) recognize a multifactorial etiology,
hereditary as well as acquired. To date several case-control studies have
documented that the condition of hyperhomocysteinemia can be considered an
independent risk factor of coronary disease and its noxious effects are dose
dependent. It exerts its effect by different mechanisms both prothrombotic and
endothelial. In our study we started from an initial cohort of 2227 subjects
(1210 males, 1017 females) aged between 45 and 64 years among which we selected
22 persons with at least 2 first-degree relatives below age 50 who had had either
a major cardiovascular event (acute myocardial infarction or sudden death) or
angiographically documented cardiac disease. We reconstructed the proper
pedigrees obtaining 22 families in whom we identified four main subgroups to
carry out analyses and comparisons: case-control, composed respectively of all
the subjects who survived a major cardiovascular event or a coronary disease
documented angiographically and clinically healthy subjects; affected line and
non affected line, composed respectively of members belonging to the family line
of the proband and members of collateral family line. Each of the subjects
involved in the study underwent a complete history regarding job and sports
activities, a standardized physical examination, 12-lead digital ECG according to
the European Standard Communication Protocol. A blood sample was taken in fasting
conditions to determine total cholesterol, HDL and LDL cholesterol,
triglycerides, glycemia, fibrinogen, plasma homocysteine. The results indicate
how among the cases there were more subjects with homocysteine higher than the 95
degrees percentile in males alone (p = 0.03), the estimated odds ratio calculated
from Fisher's test was 8.34 (95% confidence interval 1.32-52.7). Despite the fact
that mean age was significantly lower (p = 0.01) in males of the affected line
compared to those of the non affected line, the results show much higher
homocysteine values in the affected family line in both males and females: a
difference quite evident in the distribution especially as regards the 95 degrees
percentile. These results obtained in the subjects belonging to the same families
emphasize that familial aggregation, which influences the sharing of the genetic
patrimony, socio-cultural environment and food habits can induce a differential
risk for homocysteinemia. The study of mutations of genes coding for the key
enzymes of the metabolism of homocysteine, methylenetetrahydrofolate reductase
and cystathionine beta-synthase, which we prepared, will enable use to evaluate
the relative influence feeding habits and genetic factors have in the development
of hyperhomocysteinemia.
PMID- 10188335
TI - [Intracardiac ectopic thyroid: a report of a clinical case with a long-term
follow-up].
AB - We describe the prolonged follow-up of a 64-year-old female patient, with an
ectopic intracardiac thyroid gland. The mass was first detected 14 years ago,
during a routine echocardiographic examination. The patient suffered from
episodes of palpitation and cardiac auscultation revealed a systolic murmur. At
cardiac surgery a right ventricular mass penetrating most of the interventricular
septum was found. The mass was also prolapsing into the pulmonary infundibulum
and could not be removed. On histopathology examination, the presence of a normal
tissue was demonstrated. Two main clinical events characterized the prolonged
follow-up: the gradual development of a massive tricuspid insufficiency, probably
due to the strict anatomic relationship between the septal tricuspid papillary
muscle and the mass itself; frequent supraventricular arrhythmias, partially
refractory to different pharmacologic regimens, which could be ascribed to the
chronic overload of the right atrium. The mass size has been stable over the
years, and no thyroid hormone derangement was ever found.
PMID- 10188336
TI - [Radiofrequency transcatheter ablation of a bidirectional decremental accessory
atrioventricular pathway in the coronary sinus].
AB - We report the case of a 63-year-old patient who underwent radiofrequency catheter
ablation of an atrioventricular accessory pathway with bidirectional decremental
conduction properties. The successful ablation site was the distal end of a wedge
shaped dilation of the first tract of the coronary sinus. Atrioventricular
accessory pathways with anterograde decremental conduction properties was thought
to belong to fibers with Mahaim type electrophysiological properties. They rarely
show decremental retrograde conduction properties. Most Mahaim type
atrioventricular pathways are right-sided with atrial insertion points at various
sites along the tricuspid ring. On the other hand, left-sided decrementally
conducting accessory pathways are very rare. Mahaim type atrioventricular
pathways were never found in the coronary sinus. The bidirectional decremental
conduction properties and in particular the anatomic site of the atrioventricular
accessory pathway we describe in the present report are both very interesting
findings.
PMID- 10188337
TI - Elevated serum creatine kinase and MB isoenzyme levels in hypothermia--a brief
case report.
PMID- 10188338
TI - Femoral neuropathy following anticoagulant therapy: a case report and discussion.
PMID- 10188339
TI - Optimizing the use of ACE inhibitors in patients with congestive heart failure.
PMID- 10188340
TI - The HUSKY program: an opportunity to insure Connecticut's children.
AB - Uninsured children in Connecticut represent a diverse group, and insuring them is
a monumental task. In August 1997, President Clinton signed into law the
Children's Health Insurance Program, which provides $47 billion in funds to
states over the next 10 years to insure the nation's low-income children.
Connecticut has been a leader in modeling the federal Children's Health Insurance
Program into action. Connecticut's version of the program, Healthcare for
UninSured Kids and Youth, (HUSKY), was enacted over the summer, and, to date, has
enrolled over 4,000 children in the program. Connecticut's HUSKY program provides
a timely opportunity for the state, as well as community health centers and other
primary-care facilities, to reach those uninsured children in Connecticut's
communities and move the children into the HUSKY program. In order to achieve
this goal, innovative outreach strategies need to be designed that utilize
cultural and community resources to locate and insure these children.
PMID- 10188341
TI - The plaintiff's expert.
PMID- 10188343
TI - Regarding a new procedure and an old concern.
PMID- 10188345
TI - Allergy testing alert.
PMID- 10188346
TI - Bilateral acute suppurative otitis media: the stage of hyperemia.
PMID- 10188347
TI - Fungus ball sinusitis.
PMID- 10188349
TI - Tolosa-Hunt syndrome.
PMID- 10188348
TI - Vocal fold cancer presenting as sudden dysphonia in the absence of risk factors.
PMID- 10188350
TI - Alternate binaural bithermal reduced vestibular response.
PMID- 10188351
TI - A role for tonsillectomy in the treatment of psoriasis?
AB - Our objective was to determine whether tonsillectomy is beneficial in the
treatment of recurrent childhood guttate psoriasis that is associated with
recurrent streptococcal pharyngitis and tonsillitis. We retrospectively reviewed
the cases of two children who were referred to our facility for treatment of
repeated exacerbations of psoriasis and recurrent streptococcal
pharyngotonsillitis. Both patients experienced a significant improvement in their
psoriasis after undergoing adenotonsillectomy, and both were completely free of
psoriatic outbreaks after 16 months of follow-up. We conclude that tonsillectomy
appears to be of benefit in the treatment of children with recurrent guttate
psoriasis and recurrent streptococcal pharyngotonsillitis, and we hope that
further investigation will be undertaken.
PMID- 10188352
TI - The distribution of nasal erectile mucosa as visualized by magnetic resonance
imaging.
AB - We analyzed the distribution of nasal erectile tissue by reviewing five sets of
magnetic resonance imaging scans that were obtained pre- and post-decongestion.
We found that cavernous tissues were located at three sites: the inferior
turbinate, the middle turbinate, and the nasal septum. This study reaffirms the
findings of previous studies that were performed with other modalities such as
computed tomography scanning and cadaver dissections.
PMID- 10188353
TI - Spontaneous cervical hematoma: a report of two cases.
AB - Cervical hematomas are generally associated with trauma, surgery, and tumors.
Although they are rare, they can be life-threatening because they put the patient
at risk for great-vessel compression and upper airway obstruction. We describe
two cases of spontaneous cervical hematoma--one in an 81-year-old man and the
other in a 30-year-old woman. The man reported dysphonia, dysphagia, and neck
swelling of 5 hours' duration. He had been taking 100 mg/day of aspirin for a
cardiovascular condition. Examination revealed that the man had polycythemia
vera. The woman was found to have neck ache, odynophagia, and cervical
ecchymosis; portal hypertension, schistosomiasis, and blood dyscrasia were also
found. Both patients denied trauma. A suspected diagnosis of cervical hematoma
was confirmed by computed tomography, and treatment was instituted. The hematomas
resolved in about 2 weeks. The treatment of cervical hematoma is controversial,
although it is agreed that the evaluation of upper airway obstruction and its
permeability is mandatory. Surgical treatment is generally reserved for
complicated cases because of the risk of infection or bleeding.
PMID- 10188354
TI - Vocal fold granuloma induced by rigid bronchoscopy.
AB - Vocal fold granulomas secondary to endotracheal intubation, vocal abuse, and
laryngopharyngeal reflux are a well-described cause of hoarseness, generally in
the adult population. The mean age of onset is usually in the fourth or fifth
decade, and the position is most commonly on the vocal process or one of the
arytenoids. We present an atypical case involving a pediatric patient with a
large, anterior, true vocal fold granuloma following rigid endoscopy of the upper
conductive airway.
PMID- 10188355
TI - Inner ear barotrauma from scuba diving.
AB - Inner ear barotrauma among scuba divers is believed to be caused by any of three
conditions: a hemorrhage in the inner ear, a tear of the labyrinthine membrane,
or a perilymphatic fistula. These injuries may occur concurrently or separately.
Hemorrhage and membrane rupture are managed conservatively, while fistula
requires surgical repair. In this report, we describe three cases of inner ear
barotrauma in scuba divers. We also discuss the proposed etiologies of this
injury and the controversy over whether or not divers who have suffered an inner
ear trauma can safely resume scuba diving. Although the older literature clearly
suggests otherwise, we believe that scuba divers who completely recover from
inner (or middle) ear barotrauma may return to diving as long as they exercise
caution and care.
PMID- 10188356
TI - The effects of kanamycin injection into the fetal lamb cochlea.
AB - Mammalian auditory hair cells have minimal capacity for repair or regeneration
after a variety of insults, including acoustic trauma and aminoglycoside
exposure. Although fetal tissues have a greater potential for repair and
regeneration than adult tissues, there have been no reported studies on fetal
hair cell response to injury in mammals. The purpose of this research was to
investigate the effects of local application of kanamycin on fetal lamb cochlear
hair cells. Eleven fetal lambs in the early third trimester underwent kanamycin
injection through the left round-window membrane. The right ear served as a
control. Click-evoked compound action potentials (CAPs) were serially recorded in
8 fetuses. CAPs were observed in all control ears. None of the 8 kanamycin
injected ears had measurable CAPs on postoperative day 1. One kanamycin-injected
ear demonstrated definite CAPs, beginning on postoperative day 6. Hair cells were
found to be intact in 6 of 9 kanamycin-treated ears. Hair cells were missing only
in animals that went into premature labor. The presence of intact hair cells
despite the loss of measurable CAPs in kanamycin-perfused lamb cochleae was
striking. This finding may indicate that the fetal auditory epithelium is
relatively resistant to aminoglycoside injury or may be capable of prompt repair
or regeneration. Further studies on the effects of aminoglycoside injury in the
fetal cochleae seem to be warranted.
PMID- 10188357
TI - Making copies ... what is a fair charge?
PMID- 10188358
TI - Public health plague.
PMID- 10188359
TI - Claim editing abuses.
PMID- 10188360
TI - Y2K and your investments.
PMID- 10188361
TI - [Cytotoxic effect of energy supply system inhibitors on cells from Ehrlich ascite
carcinoma].
AB - It was shown that inhibitors of oxidative phosphorylation (cyanide, rotenone, and
oligomycin) and very low concentrations of exogenous prooxidants exerted a
pronounced cytotoxic effect on Ehrlich ascites carcinoma cells. We propose that
cell injury by reactive oxygen forms is the cause of the cytotoxic effect of the
studied inhibitors. It was shown via flow cytometry that inhibitors of oxidative
phosphorylation and exogenous prooxidants block cell progress in the cell cycle
and induce appearance of cells with reduced DNA content.
PMID- 10188362
TI - [Genetic structure of mobile elements of the "Penelope" family in closely related
Drosophila species].
AB - Genomic libraries were obtained from species belonging to the "virilis" group of
Drosophila. Several copies of Penelope elements were isolated from these
libraries by using a D. virilis Penelope clone as a probe. The elements were
sequenced, and their structure was determined. The geographical distribution of
this family of mobile elements in closely related species of the group was
studied in detail. Cytological localization of the elements was also carried out.
The high variability observed between different copies of Penelope is probably
due to recombination between individual copies. The role of these elements in the
evolution of closely related species is discussed.
PMID- 10188363
TI - [Systemic variations of social relationships in the two groups of Java macacas].
AB - Complex systemic variation of the style of species-specific intragroup relations
between animals was examined in two groups of stumptail macaques, comprising high
and low-status individuals. A component analysis for 17 indices of social
behavior in the studied groups showed that irrespective of the actual rank, high
status animals differed reliably from those of low status by a complex of
aggressive, affiliative, and cooperative behavioral features. The features varied
in the group in a related, rather than a random, fashion. Generally, the behavior
of the high-status females can be characterized as more "masculine," these
individuals were self-assured, oriented to dominance, showed more individual
independence and were less in need of cooperation with the other group members.
Our data confirm the hypothesis of systemic variation of social relationships at
the intraspecific level.
PMID- 10188364
TI - [Mathematical models in hemostasis physiology].
AB - A mathematical model of spatial propagation of blood coagulation is proposed. The
control mechanism of advancement of the activation zone is established. The
intrinsic and extrinsic pathways of blood coagulation are considered. Blood flow
transfer of the activated factors is shown to play a significant role in stopping
advancement of the activation zone. This effect is amplified by the coagulation
cascade. Propagation of the concentration wave is related to the model indices.
PMID- 10188365
TI - [Radionuclides 90Sr and 137Cs in the benthos near the nuclear submarine
"Komsomolets"].
AB - We have analyzed the content of radionuclides 90Sr and 137Cs in the benthofauna
and deposits near the nuclear submarine "Komsomolets." Analysis was performed on
the basis of the materials of the 31st (1993) and 36th (1995) voyages of R/V
"Akademik Mstislav Keldysh" in correspondence with the system of monitoring the
state of the abiotic and biotic situation near the nuclear submarine
"Komsomolets" (Norwegian Sea). Whereas during the 33rd voyage of this vessel
(1994) the content of these elements in the benthic animals at stations located
close to the submarine somewhat exceeded the background level of radioactivity
(Kuznetsov et al., 1996), no such excess was found during the 31st and 36th
voyages. Meanwhile, radioactive cobalt (60Co) was found in representatives of
three groups of animals during the 31st voyage at two stations located near the
submarine.
PMID- 10188366
TI - Iron-induced cytotoxicity in cultured rat retinal neurons.
AB - Oxidative stress has been proposed as a major injury mechanism in the central
nervous system including the retina. In this study, as an initial attempt to
study the mechanism of oxidative injury in the retina, we developed a cell
culture model by utilizing the iron exposure paradigm. Exposure of rat retinal
cultures for 24 hours to 10-40 MicroM ferrous or ferric chloride induced a
concentration-dependent death of retinal neurons but not of photoreceptors or
astrocytes. An antioxidant, trolox effectively attenuated the iron-induced death
of neurons and photoreceptors in a dose-dependent manner whereas neither
glutamate receptor antagonists nor cycloheximide were protective. Of retinal
interneurons, GABAergic neurons were more vulnerable to the iron toxicity than
calbindin (+) horizontal neurons. These findings show that iron exposure induces
anti-oxidant-sensitive neuronal injury in retinal culture, independent of the
excitotoxic or the apoptotic mechanisms. Of retinal neurons, different cell types
exhibit differential vulnerabilities to the iron-induced oxidative injury. This
simplified culture model system may be useful in elucidating mechanisms of
oxidative injury in the retina.
PMID- 10188367
TI - Melanosomes of retinal pigment epithelium--distribution, shape, and acid
phosphatase activity.
AB - The distribution and shape of melanosomes of the retinal pigment epithelium
(RPE), and acid phosphatase activity in melanosomes were studied in rabbits. The
rabbit eyes were observed using electron microscopy and enzyme cytochemical
electron microscopy. The majority of melanosomes were located near the apical
region of the RPE. Melanosomes in the RPE were classified as two shapes,
elliptical and spherical or oval. Elliptical melanosomes were located parallel to
the apical process and spherical or oval melanosomes were arranged vertically or
obliquely to the apical process. We think that the distribution and shape of
melanosomes contributes to the effective absorption and blocking of light coming
from all directions. Almost all of the mature and immature melanosomes we
identified showed positive in acid phosphatase reaction, indicating that
melanosomes are commonly incorporated into the lysosomal system of the RPE.
However, a few melanosomes showed negative in acid phosphatase reaction,
suggesting that some melanosomes are stable and inert. The observed premelanosome
showed negative reaction. Two types of melanosome-related complex granules were
identified; melanosomes with a cortex of enzyme-reactive material
(melanolysosome) and melanosomes with a cortex of lipofuscin (melanolipofuscin).
These findings indicate tha a relationship between melanosomes and the lysosomal
system of the RPE exists, and suggest that melanosomes may undergo modification
or degradation in the cytoplasm. Also, the observation of a premelanosome and the
positive acid phosphatase activity in mature and immature melanosomes indicates
that melanosomes of the RPE may continue to be synthesized at a low rate in adult
eyes.
PMID- 10188368
TI - The use of internal limiting membrane maculorrhexis in treatment of idiopathic
macular holes.
AB - The purpose of this study was to assess surgical results of internal limiting
membrane (ILM) maculorrhexis in macular hole surgery. This study is a part of
continuing prospective clinical trial of our team of researchers. Thirteen eyes
of 13 patients with idiopathic macular hole underwent vitrectomy with the removal
of posterior cortical vitreous, peeling of the macular ILM, and intraocular gas
tamponade, followed by postoperative face-down positioning. The excised specimens
were evaluated with transmission electron microscopy. Complete closure of the
hole was observed in all 13 eyes (100% anatomic success rate). Visual improvement
of 2 or more lines on ETDRS visual acuity chart was achieved in 11 (85%) of the
13 eyes. Six (54.5%) eyes attained visual acuity of 20/50 or better. Electron
microscopy showed ILM in the removed specimens. ILM maculorrhexis is a promising
new surgical approach to close idiopathic macular holes but requires further
investigation and long-term evaluation.
PMID- 10188369
TI - Retinopathy of prematurity-mimicking retinopathy in full-term babies.
AB - The purpose of this study was to analyze the fundus findings and associated
abnormalities in full-term babies with retinopathy of prematurity (ROP)-mimicking
retinopathy. In twenty-seven such babies suffering from this condition, retinal
findings were retrospectively analyzed. These babies were not premature and had
not required supplementary oxygen; there was no family history of the disease,
and no known causes. Bilaterality and severity of retinopathy were compared
between groups with associated systemic abnormalities and those without. Forty
eyes in twenty-seven full-term babies had abnormal retinal findings; dragged
retina accounted for 42.5%, and falciform retinal fold for 47.5%, and retrolental
membrane for 10%. Nine babies had associated brain abnormalities, and in these,
severe bilateral retinopathy was more likely to occur than in those without
abnormalities. These results suggest that if full-term babies have associated
abnormalities of the brain, the presence of retinopathy should be ascertained
postnatally by cautious examination of the retina.
PMID- 10188370
TI - The ultrastructure of corneal epithelium after co-cultivation with herpes simplex
virus.
AB - To elucidate the ultrastructural change of corneal epithelium co-cultured with
herpes simplex virus (HSV), the corneal epithelium of 3 rabbits was excised and
cultivated in culture media. After 7 days, the Kos strain of herpes simplex virus
was inoculated in the cultured cornea epithelium until cytopathic effect was
occurred. It was fixed in the solution of 3% glutaraldehyde and examined with
electronmicroscope. In co-cultured cells, the intercellular spaces had increased
and microvilli were seen prominently. The virus particles that initiated the
infection by fusing the viral envelope with the plasma membrane were also seen.
The nuclear degeneration in an infected cell was prominent. The nuclear membrane
was folded markedly, and the chromatin was degraded, condensed and displaced
toward the nuclear membrane. Numerous viral particles and inclusion bodies were
present in the nuclei. These findings suggest that the infectious process of
herpes simplex virus in the human corneal epithelium may occur in a similar way.
This result would be helpful in understanding the pathogenesis of herpes simplex
epithelial keratitis.
PMID- 10188371
TI - Streptococcal keratitis after myopic laser in situ keratomileusis.
AB - A 24-year-old healthy male underwent uncomplicated laser in situ keratomileusis
(LASIK) in left eye. One day after the surgery, he complained of ocular pain and
multiple corneal stromal infiltrates had developed in left eye. Immediately, the
corneal interface and stromal bed were cleared, and maximal antibiotic treatments
with fortified tobramycin (1.2%) and cefazolin (5%) were given topically. The
causative organism was identified as 'Streptococcus viridans' both on smear and
culture. Two days after antibiotic therapy was initiated, the ocular inflammation
and corneal infiltrates had regressed and ocular pain was relieved. One month
later, the patient's best corrected visual acuity had returned to 20/20 with
0.75 -1.00 x 10 degrees, however minimal stromal scarring still remained. This
case demonstrates that microbial keratitis after LASIK, if treated promptly, does
not lead to a permanent reduction in visual acuity.
PMID- 10188372
TI - In vivo tandem scanning confocal microscopy in acanthamoeba keratitis.
AB - The in vivo confocal microscopy technique provides us with a real-time, non
invasive way of examining the human cornea. The most important advantage of this
type of microscopy is to reveal the etiologic agents in infectious keratitis such
as Acanthamoeba keratitis. We present several representative cases of
Acanthamoeba keratitis, which were diagnosed in their early stages using in vivo
confocal microscopy and managed based on that diagnosis. In our Acanthamoeba
keratitis cases, highly-reflective round or ovoid organisms with a diameter of
about 10-25 um were visualized distinctly against relatively-dark normal
parenchymal structures, such as epithelial cells or keratocyte nuclei. Double
walled structures of Acanthamoeba cysts were clearly demonstrated in some cases.
We can confirm that in vivo tandem scanning confocal microscopy is a powerful
diagnostic tool for identifying the infecting organisms in Acanthamoeba
keratitis.
PMID- 10188373
TI - Epithelial ingrowth of anterior chamber and anterior surface of vitreous.
AB - This study is a case report of the histopathologic findings of the anterior
chamber epithelial ingrowth in a patient who had penetrating injury in the right
eye from an arrow approximately 20 years ago. The patient underwent the
enucleation in the right eye due to pthisis bulbi and was fitted with a
prosthetic eye. Specimens were prepared from the enucleated right eye for
histopathologic observation using hematoxyllin-eosin to be observed under light
microscopy. Epithelial ingrowth in the anterior chamber was noted in one layer or
multi-layered epithelial cell growth. The ingrowth had spread to the posterior
surface of the cornea to the anterior chamber angle, to the iris surface, and to
the anterior surface of the vitreous. The finding suggests that epithelial
ingrowth could invade even through a perforation site and spread wherever the
cells could reach.
PMID- 10188374
TI - Factors associated with the poor final visual outcome after traumatic hyphema.
AB - In order to determine the factors related to the worse final visual outcome
following nonperforating traumatic hyphema, the clinical characteristics of 18
patients with visual outcome of 0.1 or worse were compared with those of 166
patients with visual outcome of 0.15 or better. The presence of posterior segment
injuries such as macula edema, retinal hemorrhage, epiretinal membrane, and
choroidal rupture were significant factors of a poor final visual outcome (P <
0.01). The presence of anterior segment injuries such as corneal blood staining,
traumatic mydriasis, iridodialysis, cataract, and lens subluxation had
significant predictive factors on a poor final visual outcome and the concurrent
posterior segment injuries were more frequent in these patients. Initial visual
acuity of 0.1 or worse, glaucoma, vitreous hemorrhage, and eyelid laceration were
also significant associations of a poor final visual outcome (P < 0.05). Patients
with initially larger hyphema (grade I or more vs microscopic) and older age
group (16 years or more vs 15 years or less) tended to have poor final visual
acuities. Rebleeding was not associated with significant deterioration in visual
prognosis. We conclude that the posterior segment injuries seem to be directly
related to a poor visual outcome rather than the occurrence of secondary
hemorrhage.
PMID- 10188375
TI - Clinical characteristics of CHARGE syndrome.
AB - CHARGE syndrome, first described by Pagon, was named for its six major clinical
features. They are: coloboma of the eye, heart defects, atresia of the choanae,
retarded growth and development including CNS anomalies, genital hypoplasia
and/or urinary tract anomalies, and ear anomalies and/or hearing loss. We
experienced three cases of CHARGE syndrome who displayed ocular coloboma, heart
defects, retarded growth and development, and external ear anomalies, and we also
review the previously reported literature concerning CHARGE syndrome.
PMID- 10188376
TI - Eimeria pipistrellus n. sp. from Pipistrellus kuhlii (Chiroptera:
Vespertilionidae) in Saudi Arabia.
AB - Fecal samples from 12 Pipistrellus kuhlii captured at Shagrah, Saudi Arabia, were
examined for coccidia and three (25%) found to harbor a undescribed eimerian,
herein described as Eimeria pipistrellus n. sp. Sporulated oocysts were
subspherical, 24.8 x 23.2 (22-27 x 20-25) microns, with a bilayered and smooth
wall. The micropyle was absent, but a large oocyst residuum and a single polar
granule were present. Sporocysts were ovoid, 11.6 x 8.3 (10.5-13 x 7.5-9)
microns, with a prominent Stieda body, but without a substiedal body; sporozoites
lay head to tail in sporocysts and contained one large posterior refractile body.
Eimeria pipistrellus n. sp. is the 3rd species of the genus Eimeria found from
bats of the genus Pipistrellus.
PMID- 10188377
TI - Karyotypes on three species of Chinese mesogastropod snails, Semisulcospira
libertina, S. dolichostoma and Viviparus rivularis.
AB - Three species of the families Viviparidae and Pleuroceridae, the first
intermediate host of paragonimiasis, metagonimiasis and echinostomiasis were
studied cytologically. The observed diploid chromosome number was as follows:
Semisulcospira libertina 36, S. dolichostoma 34, and Viviparus rivularis 64. The
mitotic chromosome complement of S. libertina has nine metacentric pairs and nine
submetacentric pairs, and S. dolichostoma has three metacentric pairs and 14
submetacentric pairs of chromosomes. Viviparus rivularis showed two metacentric
pairs and 30 submetacentric pairs of chromosomes.
PMID- 10188378
TI - Effects of in vitro culture methods on morphological development and infectivity
of Strongyloides venezuelensis filariform larvae.
AB - The effects of in vitro culture methods on morphological development and
infectivity of Strongyloides venezuelensis filariform larvae (L3) to rats were
investigated. A significantly higher body length was observed in L3 from filter
paper culture (597.3 +/- 32.2 microns) than those in fecal (509.9 +/- 35.0
microns) and nutrient broth culture (503.3 +/- 31.0 microns) (P < 0.05). Larval
infectivity was assessed by exposing rats to 1,000 L3 from each culture and worms
were recovered from the lungs and small intestines. Recovery rate of these worms
did not show any significant difference. A significantly greater body length of
adults was recorded in those corresponding to the L3 harvested from filter paper
(2,777.5 +/- 204.4 microns) and nutrient broth culture (2,732.5 +/- 169.8
microns) than those corresponding to the L3 obtained from fecal culture (2,600.5
+/- 172.4 microns) (P < 0.05). Although worm fecundity and EPG counts differed
among culture methods but worm burdens and course of infection did not. These
findings suggest that the methods of cultures have a significant effect on the
morphological development of the larvae to the L3 stage, but do not influence the
infectivity to rats.
PMID- 10188379
TI - Growth and development of Gymnophalloides seoi in immunocompetent and
immunosuppressed C3H/HeN mice.
AB - The growth and development of Gymnophalloides seoi were studied in C3H/HeN mice
and effects of immunosuppression of the host on the worm development were
observed. Two hundred metacercariae of G. seoi were orally administered to each
mouse, and worms were recovered on days 1, 3, 5, 7, 14 and 21 post-infection
(PI). The worm recovery rate was significantly higher in immunosuppressed (ImSP)
mice than in immunocompetent (ImCT) mice except on days 1 and 3 PI. The worms
attained sexual maturity by day 3 PI with eggs in the uterus, and worm dimensions
and the number of uterine eggs continuously increased until day 14 PI in ImSP
mice. Worms recovered from ImSP mice were significantly larger in size than those
from ImCT mice on days 1 and 3 PI, and the number of uterine eggs was
significantly larger in ImSP mice on days 5 and 7 PI. Genital organs such as the
ovary, testes, and vitellaria, that were already developed in the metacercarial
stage, grew a little in size until day 14 PI. The results show that the C3H/HeN
mouse is, though not excellent, a suitable laboratory host for G. seoi.
PMID- 10188380
TI - Toxoplasma gondii antibody titers in sera of children admitted to the Seoul
National University Children's Hospital.
AB - A total of 542 children under 10 years of age, admitted to the Seoul National
University Children's Hospital, was examined for antibody titers of Toxoplasma
gondii using indirect latex agglutination (ILA) test. Among them, 7.7% showed
positive titers higher than 1:32, without significant difference between males
(7.3%) and females (8.5%). The seropositive rate increased with age although the
statistical significance was negligible (0.05 < P < 0.1). By residential areas,
the prevalence appeared higher among children from southern provinces (Kyongsang
do and Cholla do) than those from other areas, but the statistical significance
was also very low (0.05 < P < 0.1). When the seropositive cases were analyzed by
coincidental diseases, the prevalence was significantly higher in patients with
congenital diseases than in patients with non-congenital diseases (P < 0.05). The
results showed that the seropositive rate of toxoplasmosis in children examined
was not high compared with other endemic countries. Some correlations are
suggested between toxoplasmosis and congenital anomalies in Korea.
PMID- 10188381
TI - Age-dependent resistance to Cryptosporidium muris (strain MCR) infection in
golden hamsters and mice.
AB - An age-dependent aspect of resistance to Cryptosporidium muris (strain MCR)
infection was monitored in Syrian golden hamsters, Mesocricetus auratus, at 1-, 5
and 10-week of age and in ICR mice. Mus musculus, at 3-, 12-, and 15-week of age
orally inoculated with a single dose of 2 x 10(6) oocysts, respectively. The
prepatent periods for both animals were similar, independent of age, but the
patency was significantly longer in younger hamsters (P < 0.001) and a long
tendency in younger mice. Hamsters infected at 1-week of age excreted about 10
times higher oocysts than those at 5- and 10-week of age. However, the total
oocyst output was similar among mice of different ages. There was a good
correlation between the length of the patency and the total oocyst output in
hamsters (R = 0.9646), but not in mice (R = 0.4561). The immunogenicity of the
parasite to homologous challenge infections was very strong in hamsters and
relatively strong in mice. These results indicate that acquired resistance to C.
muris infection is age-related and the innate resistance is independent of age of
hamsters, and that both innate and acquired resistance, on the contrary, are
irrespective of age of mice.
PMID- 10188382
TI - A 54 kDa cysteine protease purified from the crude extract of Neodiplostomum
seoulense adult worms.
AB - As a preliminary study for the explanation of pathobiology of Neodiplostomum
seoulense infection, a 54 kDa protease was purified from the crude extract of
adult worms by sequential chromatographic methods. The crude extract was
subjected to DEAE-Sepharose Fast Flow column, and protein was eluted using 25 mM
Tris-HCl (pH 7.4) containing 0.05, 0.1, 0.2 and 0.4 M NaCl in stepwise elution.
The 0.2 M NaCl fraction was further purified by Q-Sepharose chromatography and
protein was eluted using 20 mM sodium acetate (pH 6.4) containing 0.05, 0.1, 0.2
and 0.3 M NaCl, respectively. The 0.1M NaCl fraction showed a single protein band
on SDS-PAGE carried out on a 7.5-15% gradient gel. The proteolytic activities of
the purified enzyme were specifically inhibited by L-trans-epoxy
succinylleucylamide (4-guanidino) butane (E-64) and iodoacetic acid. The enzyme,
cysteine protease, showed the maximum proteolytic activity at pH 6.0 in 0.1 M
buffer, and degraded extracellular matrix proteins such as collagen and
fibronectin with different activities. It is suggested that the cysteine protease
may play a role in the nutrient uptake of N. seoulense from the host intestine.
PMID- 10188383
TI - A case of gastric pseudoterranoviasis in a 43-year-old man in Korea.
AB - A case of Pseudoterranova decipiens infection was found in a 43-year-old man by
gastroendoscopic examination on August 20, 1996. On August 6, 1996, he visited a
local clinic, complaining of epigastric pain two days after eating raw marine
fishes. Although the symptoms were relieved soon, endoscopic examination was done
for differential diagnosis. A white, live nematode larva was removed from the
fundus of the stomach. The larva was 38.3 x 1.0 mm in size and had a cecum
reaching to the mid-level of the ventriculus. A lot of transverse striations were
regularly arranged on the cuticle of its body surface, but the boring tooth and
mucron were not observed at both ends of the worm. The worm was identified as the
4th stage larva of P. decipiens.
PMID- 10188384
TI - An aural myiasis case in a 54-year-old male farmer in Korea.
AB - A 54-year-old male farmer residing in Chunchon, Korea, complaining of blood
tinged discharge and tinnitus in the left ear for two days, was examined in
August 16, 1996. Otoscopic examination revealed live maggots from the ear canal.
The patient did not complain of any symptoms after removal of maggots. Five
maggots recovered were identified as the third stage larvae of Lucilia sericata
(Diptera: Calliphoridae). This is the first record of aural myiasis in Korea.
PMID- 10188385
TI - Infection status of Paragonimus westermani metacercariae in crayfish (Cambaroides
similis) collected from Bogildo (Islet), Wando-gun, Chollanam-do, Korea.
AB - During the period from October 1996 to November 1998, the infection status of
Paragonimus westermani metacercariae in freshwater crayfish (Cambaroides similis)
collected from Bogildo (islet). Wando-gun, Chollanam-do, which is known for an
endemic area of P. westermani in Korea, were examined. The average infection rate
of Paragonimus metacercariae in crayfish was 88.6%, and mean number of
metacercariae per infected crayfish was 30.2. This metacercarial density was the
highest in the group of weight in 7.1-9.0 g. These results suggest that the
natural life cycle of P. westermani is still well-preserved in Bogildo.
PMID- 10188386
TI - Characterization of YS-27, an axenic Korean strain of Entamoeba histolytica.
AB - Characterization of YS-27, an axenic Entamoeba strain, was performed by three
different laboratory methods. Zymodeme analysis using starch gel electrophoresis
and PCR with species-specific primers showed that YS-27 is a pathogenic Entamoeba
which belongs to the group II zymodeme. Pathogenicity of YS-27 was further
confirmed by observing the formation of liver abscess in Mongolian gerbils. These
results showed that YS-27 is E. hisolytica.
PMID- 10188387
TI - End-of-life issues affect nephrology nursing practice daily.
PMID- 10188388
TI - The many facets of loss: strategies for nurses.
PMID- 10188389
TI - Nephrology community initiatives to develop guidelines for end-of-life care.
PMID- 10188390
TI - When a chronic illness becomes terminal.
AB - Patients with ESRD and their families experience a variety of transitions across
the trajectory of this chronic illness. A major transition occurs when patients
who have been perceived as chronically ill become terminally ill, as changes and
complications limit options for treatment. These changes are very disruptive,
characterized by uncertainty and disturbances in the patients' prior view of
themselves. In order to restructure a new reality, patients must acknowledge the
losses and changes that have occurred. Several kinds of trigger events may
facilitate this process. Patient responses to the transition include a variety of
strategies such as seeking information, normalizing, comparing themselves to
others, and finding their identity in continuing activities or substitutes that
make them feel competent. Nephrology nurses knowledgeable about this transition
process, because of their longstanding relationships with ESRD patients and their
families, are in an excellent position to take advantage of opportunities to
provide presence, understanding, and guidance in negotiating this difficult
transition.
PMID- 10188391
TI - The final story: events at the bedside of dying patients as told by survivors.
AB - Events at the bedside of a dying patient form lasting memories for families and
friends. What is said, who is there, and how care is delivered prevail when
individuals are recalling the dying event. The La Crosse Advance Directive Study
(LADS) (Hammes & Rooney, 1998) was conducted to examine end-of-life planning in a
Midwestern community where an extensive advance directive education program
exists. The results indicated that families and friends wanted to be present at
death; wanted to give their loved one permission to die; and wanted to have
consistent, thorough, and honest communications with their providers. Families
also felt compelled to keep the promises they made to their dying loved ones.
This study provides an opportunity for families and friends to tell their stories
of the events at the bedside of dying patients. Their stories identify a need for
more medical, nursing, patient, and family education in end-of-life care.
PMID- 10188392
TI - Death with dignity.
PMID- 10188394
TI - Death and dying resources.
PMID- 10188393
TI - Legal considerations at the end of life.
AB - Patients with end stage renal disease (ESRD) and their families face questions
related to dying that are touched by legal mandates. This article addresses
patients' legal rights and the nurse's role in advocating for these rights.
Advance directives, competency to make health care decisions, assisted suicide,
disability law, and the duty to provide reasonable and safe care are specific
areas discussed in the article. Nurses must become familiar with legal
requirements; communicate effectively with patients, families, and other
caregivers; provide care that falls within the standard of care expected of
nephrology nurses; and advocate for policies that enhance ESRD patient care.
PMID- 10188396
TI - Management of the patient with ESRD after withdrawal from dialysis.
AB - When dialysis no longer achieves the goal of prolonging quality life for the ESRD
patient, withdrawal from dialysis is an option. Many patients, their families,
and caregivers cannot make an informed decision to withdraw because they do not
have sufficient information or, worse, are misinformed about what the patient
might experience. This paper reviews the clinical circumstances in which dialysis
is discontinued as well as the physiological signs and symptoms of the uremic
related death. Palliative management of those symptoms is from one nephrologist's
model and provides a starting point for dialogue about this necessary care.
PMID- 10188395
TI - Ethical decision making in nephrology nursing for end-of-life care: a
responsibility and opportunity.
AB - This article describes the ethical significance of working with ESRD patients
with a focus on end-of-life decision making. The ethical aspects of patient
advocacy are explored and suggestions are offered for helping patients make
ethically sound and caring end-of-life decisions. A model for ethical decision
making is outlined, along with guidance from the ANA Code of Ethics and
suggestions from the ANA Position Statements on Care and Comfort in Dying
Patients, Euthanasia, and Assisted Suicide.
PMID- 10188397
TI - Collaborative end-of-life decision making in end stage renal disease.
AB - Patients newly diagnosed with end stage renal disease are faced with many
treatment decisions. The decision-making process should follow some well-defined
steps. These start with the decision to initiate dialysis and may end with a 'do
not resuscitate' request or even a withdrawal from dialysis. The nephrology team
can lead the patient and family through this process by providing timely,
realistic information to help them make the best decisions. End-of-life decision
making should be a part of the initial long-term care planning done with every
patient and family.
PMID- 10188399
TI - Parenteral iron supplementation in patients with end stage renal disease.
AB - At Winthrop-University Hospital, implementation of the National Kidney
Foundation's Dialysis Outcome Quality Initiative (NKF-DOQI) is guided by the
principles of reengineering. On the basis of this model, anemia management is
entrusted to a process owner. This advanced practice nurse is empowered with the
responsibility of managing anemia and evaluated on his/her success in attaining
predetermined quality standards-including ongoing patient satisfaction. This
article examines use of the process owner position to evaluate, implement, and
proactively manage anemia-related outcomes.
PMID- 10188398
TI - Why hospice? The case for ESRD patients and their families.
AB - This article defines hospice by giving its historical context, its development
over time, and its relevancy for the end stage renal disease (ESRD) patient. A
literature review and explication of hospice usage statistics show the lack of
utilization by the ESRD community. Comparison of hospice and traditional medical
care highlights the philosophy of care over cure and hospice standards of
practice are given. Medicare rules and two case studies support the
appropriateness of hospice for ESRD patients and their families.
PMID- 10188400
TI - Collaborative care with hospice to help Richard and Irene: a case study.
AB - Pain management has been shown to be an area that has been neglected in health
care. Health care professionals need to become educated in the importance of
addressing and managing pain. Narcotic pain relievers carry many negative
connotations to both patients and health care staff. While there are many non
pharmacologic methods of pain management that should be incorporated into patient
care, medication management is an area with which we must be comfortable.
PMID- 10188401
TI - Process owners: empowering nurses to manage anemia. Case study of the anemic
patient.
AB - At Winthrop-University Hospital, implementation of the National Kidney
Foundation's Dialysis Outcome Quality Initiative (NKF-DOQI) is guided by the
principles of reengineering. On the basis of this model, anemia management is
entrusted to a process owner. This advanced practice nurse is empowered with the
responsibility of managing anemia and evaluated on his/her success in attaining
predetermined quality standards--including ongoing patient satisfaction. This
article examines use of the process owner position to evaluate, implement, and
proactively manage anemia-related outcomes.
PMID- 10188402
TI - The dilemma of "the last access site".
PMID- 10188403
TI - Agonist narcotics.
AB - Pain management has been shown to be an area that has been neglected in health
care. Health care professionals need to become educated in the importance of
addressing and managing pain. Narcotic pain relievers carry many negative
connotations to both patients and health care staff. While there are many non
pharmacologic methods of pain management that should be incorporated into patient
care, medication management is an area with which we must be comfortable.
PMID- 10188404
TI - A practical guide to funeral planning.
PMID- 10188405
TI - Whose life is it anyway?
PMID- 10188406
TI - Discussion paper--proposed national organisation for critical care nurses in
Australia.
AB - The following discussion outlines the various issues considered in the process of
working towards establishing a single, national professional organisation for
critical care nurses throughout Australia. This paper outlines the background and
results of the previous survey and summarises the salient features of the draft
constitution. The proposed structure of CACCN Inc. under the new national
organisation is diagrammatically represented in Appendix 1, with the full draft
constitution available on the CACCN Web site at or by
contacting the national office.
PMID- 10188407
TI - Pioneering the 12-hour shift in Australia--implementation and limitations.
AB - Twelve-hour shift rostering offers an alternative to the traditional 8- and 10
hour shifts usually worked in Australian nursing practice. This paper outlines
the implementation process involved in introducing 12-hour shifts in a Melbourne
hospital intensive care unit. The process was instigated by the nursing staff.
After extensive consultation with the union and hospital management, a roster
pattern of two 12-hour days, followed by 12-hour night shifts then days off, was
introduced. Independent researchers were engaged to evaluate the impact of the 12
hour shifts on staff well-being and work performance. Effects on staff retention,
sick leave and inservice education were examined. The researchers found that well
being and work performance were minimally affected by the 12-hour shift roster,
while staff retention and sick leave were unaffected. Further, the pattern of 12
hour shifts, which was democratically implemented, was preferred by the nursing
staff and did not diminish their well-being and work performance.
PMID- 10188408
TI - Withdrawal of life-support treatment: the experience of critical care nurses.
AB - Technological advances in health care have made it possible to restore and
prolong life for patients who would have died in the past. Unfortunately, one
consequence of this is that some patients linger in intensive care units (ICUs),
dependent on the technologies but with no hope of recovery. Therefore, decisions
regarding withdrawal of life-support treatment are increasingly being faced by
the health-care team. This study aimed to explore the lived experience of
critical care nurses who had cared for patients during withdrawal of life
support. The methodology employed was interpretive phenomenology. Interviews were
conducted with seven critical care nurses, with the meanings of the experience of
withdrawal of life-support treatment for these nurses extrapolated from the
narratives and clustered into themes. The study highlighted the importance of
honest communication during the processes of decision-making and withdrawal of
treatment. It was important for these nurses to be sure that family members were
well-informed regarding the process of withdrawal of life-support treatment and
that they could provide support and ensure that the patient's comfort and dignity
were maintained during the process. The need to debrief after the event became
evident but formal debriefing processes were rarely undertaken.
PMID- 10188409
TI - The critical care nurse's role in preventing secondary brain injury in severe
head trauma: achieving the balance.
AB - Secondary brain injury is associated with a reduction in cerebral blood flow,
oxygenation and perfusion related to hypotension, hypoxemia and raised
intracranial pressure. This has been confirmed on autopsy and is associated with
a higher mortality rate, as supported by many studies. The primary goal of
nursing management in severe head trauma is to maintain adequate cerebral
perfusion and improve cerebral blood flow in order to prevent cerebral ischaemia
and secondary injury to the brain. This literature review included a Medline and
CINAHL search for published and unpublished research, a manual search of recent
literature, a citation review of relevant primary and review articles, contact
with primary investigators and clinical observation of case studies using the
latest cerebral perfusion research technology. Expert critical care nurses were
observed and their practice noted as they cared for severely head-injured
patients. The majority of the evidence was derived from class II and class III
classifications, which provide guidelines and options for practice. Nursing and
medical management were found to overlap, with the focus for the nurse being an
integrated balance of scientific, technical and humanistic management. The
nurse's role is extremely important because the expert nurse cognitively
manipulates many variables over a continuum of care and, if such tasks are
skillfully and successfully performed, the incidence of secondary brain injury is
reduced.
PMID- 10188410
TI - Nurses' responses to acute severe illness.
AB - The medical emergency team (MET) at Liverpool Hospital superseded the cardiac
arrest team in 1990 and can be summoned by any staff member who identifies a
patient at risk according to preset criteria; for example, severe hypotension.
Weekly reviews of MET calls have identified clinical antecedents present prior to
the patient's condition deteriorating to a critical level. This study assessed
the responses of nurses in the presence of these warning signs. Medical records
of 178 patients who required MET assistance during 1994 were retrospectively
reviewed. A data collection form designed for the study sought demographic
information, time and location off the MET call and documented patient complaints
for the 24 hours preceding the MET call. Also collected was information on who
was contacted as a result of the critical observation. Analysis included
frequencies, percentages, means and standard deviations, including location, type
and timing of the MET call. MET calls occurred in the general wards (50 per
cent), emergency department (42.3 per cent) and other areas (7.7 per cent). The
four main categories of emergency comprised cardiac arrest (25.6 per cent),
airway/breathing problems (22 per cent), decreased level of consciousness (20.8
per cent) and 'other', including prolonged chest pain, fitting and hypotension
(31.6 per cent). The predominant response to a clinical antecedent was to call
the MET (68.4 per cent). Other responses resulted in delays of 1 hour (18 per
cent) and up to 3 hours (8 per cent) on some wards before treatment specific to
the clinical antecedent commenced. A need to educate health professionals
regarding the warning signs of acute severe illness and when to summon assistance
has been identified.
PMID- 10188411
TI - Carpe diem! "Seize the day"
PMID- 10188412
TI - Transient osteoporosis during pregnancy: the perioperative nurse's role.
AB - Perioperative nurses are confronted with ever changing demands in their daily
practice. Perhaps the greatest challenge, however, is in the care of patients
with multi-faceted health problems. These patients require the coordination of
many multi-disciplinary team members in attempting to achieve optimum health.
This paper will describe the case study of a 28 year old, 26 week primip, who
presented to a tertiary care centre with spontaneous bilateral hip fractures of
unknown origin. It will further discuss the disease process known as Transient
Osteoporosis during Pregnancy, the surgical approach, and finally, the role of
the perioperative nurse in coordinating the patient's perioperative care.
PMID- 10188413
TI - Predicting difficult airway access in the preoperative clinic.
PMID- 10188414
TI - Lymphatic mapping and sentinel node biopsy. New technology for women's health.
AB - The current surgical standard of care for the management of invasive breast
cancer is the complete removal of the cancer with documented negative margins by
either mastectomy or lumpectomy followed by complete axillary lymph node
dissection. These procedures can be associated with significant morbidity which
leads to increased hospitalizations, increased overall costs and considerable
discomfort and life-style changes for the patients. With sentinel node
identification and biopsy, patients with probable negative lymph nodes may avoid
axillary dissection, and easily be treated as outpatients.
PMID- 10188415
TI - Professional practice issues.
AB - The value in exploring nursing issues was publicly demonstrated in 1997 when
Winnipeg perioperative nurses told of their struggle with the personal impact of
professional practice issues in their workplace. Nursing issues are matters of
dispute within and affecting the nursing profession. Issues evolve because of
value differences which emerge as part of one's socialization process or develop
as a by-product of one's life experience. The author revisits a personally
experienced nursing issue and explores it according to Bowman's plan.
PMID- 10188416
TI - Multiple organ retrieval and exchange program.
PMID- 10188417
TI - As boundaries soften...
PMID- 10188418
TI - Snoezelen and chronic pain: developing a study to evaluate its use (Part I).
AB - Chronic pain can be devastating, it impinges upon the life of the sufferer,
causing psychological, physical, social and financial problems, leaving the
individual searching for an explanation and a cure. Although there are no major
epidemiological studies to date, it has been suggested that the impact of chronic
pain, not only to the patient, but also to society and the NHS is phenomenal,
with loss of production and costs of treatments (Fordyce 1995). Specialists
within the field of chronic pain have advocated the use of the multidisciplinary
approach to deal with the problems and thus suggest the use of the pain
management programme, which is designed to teach the patient coping strategies.
Recently, however, there has been a call within the literature to identify the
effectiveness of singular strategies, which may be equally as effective and less
expensive (Keefe et al 1992). The purpose of these papers is to introduce one
such strategy, which has been evaluated over the past four years in order to
investigate the use of the sensory environment (Snoezelen) for the management of
chronic pain. In part II of this paper, an evaluation of Snoezelen and chronic
pain will be presented, along with the findings of an investigation into its use.
PMID- 10188419
TI - Rituals: the 'soul' purpose.
AB - Nursing has, perhaps unknowingly, given recognition to the importance of
maintaining the client's normal rituals and patterns of day-to-day activity on
admission to hospital. To make the client feel more at ease, comfortable and
relaxed, care is aimed at adhering to their usual routine. To this end, the
client's bedtime rituals, toileting habits and many other of their daily routines
are explored during the hospital admission process or initiation ceremony to the
ward. As nurses, we place great meaning on trying to maintain these rituals and
routines for the client, recognizing that keeping a sense of normality may be of
great importance. It seems almost paradoxical then, that it is we nurses who
criticize ourselves for compulsively adhering to what are described as
ritualistic ways of working; which it has been said, are of seemingly little
value both to the client's own healing process and nursing itself. In a recent
paper the notion that ritualized practice had no place in nursing and made a case
for the defence of rituals was challenged. This paper expands this theme further,
exploring the symbolic and ancestral necessity for rituals, drawing upon
archetypal psychology to help illustrate the potential hazards for the nursing
milieu of dismissing rituals without fully understanding their latent purpose.
PMID- 10188421
TI - Complementary therapies on the NHS: current practice, future developments (Part
I).
AB - Three major reports have been published within the past year on the status, use
and development of complementary medicine within the UK. The NHS Confederation
has undertaken a survey of usage within NHS services in Leicestershire, the
Foundation for Integrated Medicine has explored how such services might be
improved, and the University of Exeter was commissioned by the Department of
Health to survey complementary medicine organisations. In Europe, complementary
medicine has been the focus of considerable discussion, little of it very
positive. This paper examines what we now know about the use of complementary
medicine within the NHS, and explores the notion of 'integrated medicine'. A
second paper, to be published in August, will look at the status of complementary
medicine in the UK and Europe, and important developments regarding the future of
practitioner training.
PMID- 10188420
TI - Complementary therapies: making a difference in palliative care.
AB - Palliative care is concerned with people who have a life-threatening illness and
has been at the forefront of incorporating complementary therapies into orthodox
care. The reasons why such people are likely to seek out complementary therapies
and recent research that links the two movements are discussed. The main focus is
on the innovative programme of complementary therapies offered to both patients
and carers by North Devon Hospice. Thirty-eight patients and carers discussed the
provision of complementary therapies in focus groups. The therapies were seen as
being an integral part of the Hospice's provision and valuable as a means of
introducing people to other services offered by the Hospice. Both potential
benefits and possible problems are also discussed. Suggestions are made for
expanding the provision of the therapies and to improve access to them.
PMID- 10188422
TI - Nurses' assessments and management of pain in children having orthopedic surgery.
AB - The specific aims of this research project were to (a) describe selected verbal,
nonverbal, and physiological arousal indicators of the child's pain; (b) describe
which pain indicators were most influential to nurses in decision-making about
interventions for managing the child's pain; (c) describe pain interventions used
by nurses; (d) compare postoperative analgesic orders to recommended dosages for
the children; and (e) explore relationships between the child's self-report of
pain and medication dosages administered. Subjects included 19 children aged 5-17
years who experienced 20 orthopedic surgical procedures (one child had two
surgeries one week apart). Data were collected by staff nurses for the first five
days after surgery. Pain levels were reported using the Oucher Scale.
Postoperative pain was reported at moderate levels and showed only a gradual
decrease throughout the hospital stay. Nonverbal pain indicators included crying
and tense face. The child's complaint of pain and reported Oucher scores were
most influential in influencing nurses to intervene in the child's pain.
Nonpharmacological comfort measures included positioning and reassurance. All
children received medications for pain; 49% of the orders were within the
recommended therapeutic dosage range. A small but significant correlation was
found between the child's reported pain level and the morphine equivalents of
pain medication received. Recommendations included development of nursing flow
charts that provide space to record pain levels and nursing interventions, in
service education for nurses on nonpharmacological interventions, and further
research with a larger sample and a single pain rating scale.
PMID- 10188423
TI - Factors perceived to influence parental decision-making regarding presymptomatic
testing of children at risk for treatable adult-onset genetic disorders.
AB - The purpose of this study was to identify those critical factors that genetic
nurse experts perceived could influence parental decision-making to seek or to
reject presymptomatic testing of their children at risk for treatable adult-onset
genetic disorders (neurofibromatosis 2, familial adenomatous polyposis, and von
Hippel Lindeau disorder). Perceptions of ISONG genetic nurse specialists were
surveyed through a modified Delphi technique and four major themes emerged:
personal experience with severity of genetic disorder, receiving accurate
information from credible sources, availability of quality treatment, and risk
perception. Currently, there is a paucity of extant research that identifies
critical factors influencing parental decision-making about this relatively new
testing alternative for children. Thus, these experts are an important source of
valuable information needed to identify such factors. Findings may be useful to
design a qualitative study with parents to investigate this issue.
PMID- 10188424
TI - Heart healthy eating behaviors of children following a school-based intervention:
a meta-analysis.
AB - The purpose of this meta-analysis was to estimate the effects of school-based
interventions on heart healthy eating behaviors of fourth and fifth grade
students. The overall effect size (d value) across 12 studies was .24. The 95%
confidence interval ranged from .174 to .301. It can be concluded that the school
based cardiovascular health promotion programs had a significant effect on the
heart healthy eating behaviors of student participants. Recommendations include
identification of reliable measures and inclusion of culturally diverse
populations in future studies.
PMID- 10188426
TI - A personal philosophy and model of nursing.
AB - Understanding the relationships and conflicts between nursing professionals,
their health care clients, wellness, and the environment is a major component of
any nursing philosophy. This understanding is a fundamental element in The Brown
Human Cell Model, a personal philosophy of nursing. The objectives of this model
are to assist in obtaining a clearer understanding of the conflicts the nursing
professional will encounter with the health care clients, their wellness, and
environment. Nursing, client, wellness, and environment are defined according to
the personal attitudes, behavior, beliefs, and values of the author. Many factors
and essential components were borrowed from other nursing theories in forming
this philosophy and model. The model is a replica of a human cell, significant in
defining how nursing, client, wellness, and environment relate to a continuum of
health.
PMID- 10188425
TI - Spasticity in children with cerebral palsy: a retrospective review of the effects
of intrathecal baclofen.
AB - The administration of baclofen by intrathecal pump is a new technique used to
reduce spasticity for individuals with upper motor neuron system injuries.
Children with cerebral palsy often have difficulty in mobility because of this
form of spasticity. The purpose of this study was to assess the functional
outcomes of intrathecal baclofen pump therapy with spasticity in children with
cerebral palsy. A retrospective review of medical records for pediatric cerebral
palsy patients receiving intrathecal baclofen for intractable spasticity was
performed. Of 23 sequential medical records meeting requirements for inclusion in
the study, 17 subjects had sufficient recorded data to be included in the study.
Data from the medical records included Ashworth scores, therapy complications,
and changes in mobility and independence. Although no significant changes in the
upper extremities with intrathecal baclofen occurred at one and three months, the
trial bolus showed statistically significant changes in mean Ashworth scores. The
pre- and posttrial bolus Ashworth scores for the lower extremities showed
statistically significant decreases in the posttrial scores and at one and three
months when compared with the pretrial scores (p < .001). Complications were
resolved with conservative management without long-term sequelae. No infections,
respiratory depressions, or deaths occurred as a result of intrathecal baclofen
therapy in this study. Although intrathecal baclofen had a significant effect in
reducing lower extremity spasticity in children with cerebral palsy, further
prospective studies are needed to determine the effects of intrathecal baclofen
on such indicators as activities of daily living.
PMID- 10188427
TI - African American women's health self-assessment: health status and the sense of
coherence.
AB - This descriptive study examines the relationship between health self-assessment,
health status, and the sense of coherence (SOC) in a random sample of 48 African
American women. Sense of coherence and health status were measured by
Antonovsky's Orientation to Life Questionnaire and the Perception of Health
Status Scale, respectively; health self-assessment was determined by placement on
a rung of the Cantril ladder. Women who viewed their current health status as
devoid of acute, chronic, or serious health problems had a significantly stronger
SOC than those with serious, chronic, and degenerating health problems.
Generally, women did not differ on the meaningfulness they attached to their
lives based on their health status; however, women with no acute health concerns
and those with serious health problems differed significantly on this subscale.
The women's SOC was significantly different based on the amount of pain being
experienced, particularly on the manageability scale, indicating their inability
to handle pain. The women's overall health self-assessment was negatively related
to their SOC. A strong SOC was negatively related to two dimensions of health
status: perception of pain and current health status. A strong SOC was negatively
related to overall health status. Implications to promote the health of African
American women are discussed.
PMID- 10188428
TI - Biological and environmental influences in mental health care.
AB - Principles of Preventive Psychiatry offer a logical and economical approach to
mental health care delivery. This article describes two perspectives on mental
health care, biological and environmental. If mental illness and related distress
are perceived as biologically based, the problems are thought to be under the
skin. They can then be treated with chemicals and other scientific technologies.
On the other hand, if mental illness and related distress are perceived as
developing from environmental factors, the problems are thought to be linked to
forces external to the individual. Treatment is addressed by a modification in
the environment. This approach requires changes to public policy and legislative
mandates. Mental health issues including, suicide, runaway youths, homicide, the
elderly and other disenfranchised groups prevalent in American society are
highlighted. An integration of the biological and environmental perspectives is
delineated as an approach to early diagnosis, effective treatment, and
rehabilitation. Recommendations are presented that focus on population-specific
interventions necessary to effectively address these conditions.
PMID- 10188429
TI - AIDS: risk behaviors and situations as perceived by adolescents in Gaborone,
Botswana.
AB - While AIDS continues to escalate in Botswana, no systematic investigation has
been done of the contextual (behavioral and situational) variables important to
the tailoring of AIDS educational prevention program for adolescents. A cross
sectional descriptive study identified the specific behaviors and situations
placing adolescents at risk for AIDS as perceived by a convenience sample of 48
adolescents. Adolescents attended gender-specific focus groups and completed a
demographic questionnaire. Content analysis revealed that gender and age could
categorize the adolescents' perceptions of contextual variables. For younger
adolescents AIDS-related behaviors involved sex and intravenous drug use; for
older adolescents AIDS-related behaviors involved multiple sexual partners and
sexual relationships between older men and adolescent girls. Though a consensus
existed regarding the situational variables, gender and age influenced the
situation that was most challenging to these adolescents. The data support that
AIDS educational prevention programs must be tailored to the adolescents' gender
and age.
PMID- 10188430
TI - Breast cancer screening among African American women: addressing the needs of
African American women with known and no known risk factors.
AB - Breast cancer is the single most common form of cancer observed in African
American women. Yet, in spite of the advances that have been made in the area of
breast cancer detection and treatment, breast cancer continues to be their
leading cause of cancer death. Many experts believe that breast cancer mortality
among African American women could be significantly reduced if breast cancer
screening recommendations were more effectively used. However, little is known
about the breast cancer screening behaviors of women with known and no known risk
factors. An exploratory study was therefore undertaken to gain a broader
understanding of the breast cancer screening behaviors of African American women.
Attempts were also made to determine if age, type of medical services used,
breast cancer risk factors, or provider discussions influenced compliance with
screening guidelines. Breast cancer screening procedures were found to be
markedly under-used by the African American women in the study sample. However,
the data suggested that if health care providers provide women with information
regarding their personal breast cancer risk and make a personalized
recommendation for their breast cancer screening, greater compliance with
screening guidelines would occur.
PMID- 10188431
TI - Nursing students' perceptions regarding differences in the clinical learning
experience that relate to minority-racial status.
AB - The need to obtain information about students' perceptions regarding differences
in clinical learning that relate to minority-racial status was part of the
impetus for a larger study (Anfinson, 1993). A naturalistic inquiry paradigm was
used for this study. The analysis of the qualitative data was completed by using
the constant comparative/grounded theory approach of Stauss and Corbin (1990).
One NLN accredited associate degree nursing program, eight first-level student
nurses and four staff nurses were participants in the study. From the field notes
of student observations in the clinical setting, tape recordings of the student
interviews and other artifacts, the analysis demonstrates differences in
students' perceptions. The differences in students' perceptions related to
minority-racial status can be attributed to how it was viewed, e.g., as a
previously acquired attitude, or related to the evaluation process. Discussions
of ways to assure that race and ethnicity do not play a role in evaluation of
minority students are presented. Based on the literature and personal
experiences, the author maintains that commitment of faculty and clear
communications are primary factors in promoting minority student success.
PMID- 10188432
TI - Expanding opportunities in graduate education for minority nurses.
AB - Unique opportunities exist in education for minority nurses in graduate and
doctoral programs. Graduate enrollment statistics reported by the American
Colleges of Nursing (1996) showed that from 1991 to 1995 minority nursing
enrollment in masters degree programs averaged 11% of total graduate nursing
enrollment, with a mean of 3,392 students, compared to an average of 83% non
Hispanic White masters in nursing degree graduate enrollees, with a mean of
24,941 students. During this same period, minority doctoral nursing student
enrollment showed an average figure of 33 enrollees or 9% of the enrolled nursing
doctoral population, while non-Hispanic White doctoral nursing student enrollment
figures showed enrollment averaging 2,333 student or 81% of the enrolled nursing
doctoral population. These figures represent over 70% enrollment differences in
minority and non-Hispanic White graduate and doctoral student enrollment. This
article addresses the disparity in graduate nursing education and outlines
strategies to provide an equitable approach to the educational dilemma faced by
minority nurses.
PMID- 10188433
TI - Nursing careers for the homeless: a curriculum for success.
AB - The Nursing Careers for Homeless People Project (NCHPP) is a comprehensive multi
dimensional academic and social strategy designed to assist homeless individuals
who have an interest and aptitude for nursing to achieve career mobility in
nursing. NCHPP is a 2-phase project: (1) a Pre-Admission Readiness Program (PRP)
and (2) the Collegiate Phase. The 3-month PRP focuses on socialization to
nursing, building self-concept, academic enhancement, and career exploration. The
Collegiate Phase includes academic, social, and financial support, as well as
assistance with job placement and follow-up. NCHPP has enrolled 96 students to
the PRP since 1994 and graduated 70 students or 73%. Fifty-three percent of the
PRP graduates were admitted to a Bachelor of Science (BS) or Associate of Science
(AS) program in nursing, and 54% of the PRP graduates are employed in health
oriented positions. Two students from the first group of PRP graduates are
scheduled to receive the degree of Bachelor of Science in Nursing in May 1999.
There have not been any graduates from associate degree programs due to part-time
attendance, long waiting lists for entry into the nursing program, and transfer
of students from the AS program to the BS program. Although there are many
challenges and obstacles faced by homeless people, the NCHPP has succeeded in
decreasing welfare rolls, unemployment, and poverty.
PMID- 10188434
TI - Pediatric sledding injuries in Pennsylvania.
AB - OBJECTIVE: To describe the frequency, characteristics, and circumstances of
pediatric sledding-associated injuries and to assess the validity of published
risk factors and prevention measures for these injuries. METHODS: A
retrospective, descriptive study of patients admitted to the 25 accredited trauma
centers in Pennsylvania. RESULTS: Two hundred twenty-six patients were admitted
for sledding-related injuries. Sixty-nine percent were male. The mean ICU LOS was
1.2 days (SD = 3), and the mean hospital LOS was 7 days (SD = 7.2). Ninety-eight
percent were discharged alive. Forty-seven percent of the ISS scores were
classified as moderate (ISS 7-15). There was almost no correlation between age
and ISS (r = 0.06), but there was moderate correlation between ISS and length of
ICU stay (r = 0.47). Hitting trees and stationary objects (n = 121) was the most
common circumstance of injury. Patients struck by moving vehicles (n = 16) had
the highest proportion of head (30%) and chest (15%) injuries, the highest
mortality rate (33%), the highest median ISS score (20) and the highest mean ICU
LOS (6.4 days) compared to patients who hit stationary objects or fell.
CONCLUSIONS: Among children admitted to Pennsylvania trauma centers, most
sledding injuries were of a mild and moderate severity and required an average of
a week's hospitalization. Most children were injured from collision with
stationary objects, supporting the precaution against sledding in areas with
obstacles. The high mortality rate from motor vehicle/sled collisions justifies
the prohibition against sledding in areas with moving vehicles.
PMID- 10188435
TI - The effects of familial voice interventions on comatose head-injured patients.
AB - PURPOSE: Opportunities for family interaction with comatose patients are often
strictly limited. Some studies have indicated that family visits to the ICU have
detrimental effects on physiologic parameters such as blood pressure and heart
rate. This study was undertaken to investigate the effects of taped messages by a
family member on key measures of physiological functioning in comatose head
injured patients in intensive care units. METHODS: A convenience sample of 10
comatose patients was used. Paired t-tests were performed to determine changes in
physiologic measures with the introduction of family member taped messages.
FINDINGS: None of the subjects exhibited any statistically significant variables
in physiologic criteria after introduction of the tapes. CONCLUSIONS: Research to
date represents conflicting results. This study demonstrated no untoward effects
with exposure to taped familial messages, including no changes in intracranial
pressure (ICP), blood pressure, pulse, respiratory rate, mean arterial pressure,
oxygen saturation level, or level of restlessness. The findings support allowing
family interactions with comatose head-injured patients in the ICU.
PMID- 10188436
TI - The top 10 pressure-ulcer prevention and skin-care strategies for trauma
patients.
PMID- 10188437
TI - Tools for quantifying trauma resuscitation videotapes for performance
improvement.
PMID- 10188438
TI - President Clinton endorses Consumer Bill of Rights.
PMID- 10188439
TI - Trauma coordinator: full-time or part-time?
PMID- 10188440
TI - Comparative study of risk factors for skin breakdown with cervical orthotic
devices: Philadelphia and Aspen.
AB - PURPOSE: To compare risk factors for skin breakdown between Philadelphia and
Aspen cervical collars. METHODS: Crossover design. Twenty healthy volunteers wore
Philadelphia and Aspen cervical collars in random order. Occipital pressure,
relative skin humidity, and skin temperature measured at 0 and 30 minutes. Paired
t-tests compared changes between collars from 0 to 30 minutes. FINDINGS:
Occipital pressure and skin temperature were not statistically different between
collars. Relative skin humidity increased more in Philadelphia (29% +/- 17%) than
Aspen (8% +/- 9%), p < 0.001. CONCLUSIONS: Aspen resulted in lower relative skin
humidity.
PMID- 10188441
TI - Ultrasound evaluation of abdominal trauma in the emergency department.
AB - To review the use of ultrasound for assessment of abdominal trauma during the
secondary assessment. Three current methods for evaluation of abdominal trauma
will be outlined. The use of ultrasound in evaluation of patients with blunt
abdominal trauma will be highlighted, including performance of test, time to test
completion, strengths, and limitations. The use of serial examination utilizing
focused abdominal sonography for blunt trauma (FAST) to evaluate hemoperitoneum
will be presented.
PMID- 10188443
TI - Mohs wounds of the forehead: healing by secondary intention.
AB - Accurate prediction of the course of wound healing allows patients with Mohs
surgical wounds on the face to be objectively selected either for surgical repair
or for spontaneous healing. Parameters affecting wound healing--location, depth
and size of wound--were documented at intervals for 135 patients who had full
thickness defects in the forehead after Mohs surgery, which were left to heal by
secondary intention. Quality of cosmesis was determined at least four months
after surgery. Final cosmetic result was predictable on the basis of wound
location, size and depth. Allowing selected Mohs surgical wounds to heal
spontaneously offers optimal cancer surveillance, simplified wound care and
elimination of reconstructive procedures along with their associated costs and
potential complications.
PMID- 10188442
TI - The nonoperative injury pathway.
PMID- 10188444
TI - The role of moist wound healing in the management of meningococcal skin lesions.
AB - This report describes the management of haemorrhagic skin lesions in a patient
with meningococcal meningitis.
PMID- 10188445
TI - The characteristics and formation of granulation tissue.
AB - An overview of the processes involved in the formation of healthy granulation
tissue in a wound and factors affecting its management.
PMID- 10188446
TI - Management of venous leg ulcers.
PMID- 10188447
TI - The use of larval therapy in wound management.
AB - An update and detailed guide on the use of sterile larvae in chronic or infected
wounds.
PMID- 10188448
TI - Effect of chronic wound fluid on fibroblasts.
AB - This study examines how the microenvironment created by fluid in chronic wounds
influences the growth of dermal fibroblasts. Newborn fibroblasts, which are known
to grow rapidly, were used as a model system to explore how chronic wound fluid
affects the growth of regenerative fibroblasts. Wound fluid was collected from
patients with chronic venous leg ulcers (duration longer than two months). The
biological properties of this fluid were then further characterised to elucidate
its molecular effects on cell growth. Results indicate that chronic wound fluid
dramatically inhibited the growth of newborn dermal fibroblasts. This growth
inhibitory effect was variable among donors, reversible and heat-sensitive. The
inhibitory effect was due not to cytotoxicity or impaired plating efficiency of
these cells, but to specific interference with the cell cycle. Chronic wound
fluid arrested newborn fibroblast growth by preventing entry into the S-phase, or
DNA synthesis-phase, of the cell cycle. In contrast to its effects on newborn
fibroblasts, chronic wound fluid either stimulated or had a minimal effect on
fibroblasts which had been cultured from the edge of chronic venous leg ulcers
and healthy tissue on the upper thigh in the same patient. This may partially
account for the impaired healing seen in chronic venous leg ulcers.
PMID- 10188449
TI - The use of growth factors in clinical practice.
AB - The second in a two-part article reviewing the current and potential role of
growth factors.
PMID- 10188450
TI - Using photoplethysmography as part of nursing assessment.
AB - A review of the literature on the use of photoplethysmography as an assessment
tool to identify the presence of venous insufficiency.
PMID- 10188451
TI - [Taking charge of a child from the operating room according to department
standards].
PMID- 10188452
TI - [Relevance and acceptance of nursing standards--shown in a pediatric intensive
care unit].
PMID- 10188453
TI - [New fixation methods for orogastric feeding catheters in newborns and premature
infants].
PMID- 10188454
TI - [Care planning and report in incurable metabolic disease (Gaucher's disease)].
PMID- 10188455
TI - [Report from a children's home in Roumania].
PMID- 10188456
TI - [Health risks in standing occupations].
PMID- 10188457
TI - [Is pediatric home care an alternative to the pediatric hospital?].
PMID- 10188458
TI - [Sleep disorders in children].
PMID- 10188459
TI - [At last, here they are! Leaflets on accidents in children--early diagnoses].
PMID- 10188460
TI - [Toxic and less toxic plants. 41].
PMID- 10188461
TI - [Protection of mothers is a constitutional law and a nucleus of labor protection
rights of women].
PMID- 10188462
TI - Statistics or not statistics? That is the question.
PMID- 10188463
TI - Assessment of clinical skills: a new approach to an old problem.
AB - The changed nature of clinical placements, with shorter in-patient episodes and
staff in clinical areas carrying increasingly high workloads, has prompted
changes in the teaching learning and assessment of clinical skills. The 'Bart's
Nursing OSCE' is an innovative approach to the assessment of clinical skills,
through the medium of simulated professional practice. The antecedents of this
educational development are discussed before detailed description of the Bart's
Nursing OSCE. Discussion focuses upon: the rationale, authenticity, validity and
reliability of the assessment; the roles of assessors and simulated patients;
feedback to and from students and other stakeholders; the educational impact of
the innovation; and management issues.
PMID- 10188464
TI - Community nurses' experiences of distance learning: implications for autonomy and
dependence.
AB - This study examines the experience of a group of students studying a range of
health modules by distance learning. The sample included qualified community
nurses who were studying a distance-learning research-awareness course in order
to convert their community qualification to diploma level and nurses who were
studying a range of distance-learning courses as access to a BSc(Hons) in
Community Health. Modules studied included a range of 15 credit diploma-level
modules in health subjects and a 30-credit research-awareness module. One hundred
and twenty questionnaires were distributed generating an 80% response rate.
Results revealed a preference for flexible but highly structured materials with
clear assignment guidance and support. The results raise important issues in
relation to autonomy and dependence and how this may interact with learning style
and approaches to study.
PMID- 10188465
TI - Evaluation of the use of a skills acquisition manual within the common foundation
programme for pre-registration nursing.
AB - A skills acquisition manual had been developed for use in the common foundation
programme. This article describes an evaluative study of the use of this manual
by two cohorts within the pre-registration programme. Information was gained by
analysis of the skills acquisition manual and interviewing a sample of
participants from both the student cohorts, clinical staff and lecturers involved
with the programme. Findings identify a number of issues of interest and
demonstrate that the range of clinical opportunities within the common foundation
programme enable students to achieve a wide range of transferable skills within a
programme that reflects all aspects of nursing.
PMID- 10188466
TI - Learning on clinical placement: the experience of six Australian student nurses.
AB - Concerns about the adequacy of clinical education in nursing courses in Australia
have escalated since the transfer of pre-registration nursing education into the
tertiary sector. This descriptive, interpretative study, informed by the
tradition of critical social science, sought to understand the clinical learning
experiences of undergraduate nursing students. At the same time, it fostered an
active participation of students in their own learning. Daily post-clinical
conferences with the students were taped and transcribed verbatim to provide data
for the study. Additional data was collected from informal discussions and
observations of the students during the placement. Analysis revealed three main
categories, which reflected the students' experiences. These included: (1) I
don't belong; (2) doing and practising: progress at last; and (3) transitions in
thinking. Feeling part of the team was closely linked to the opportunity to
learn, emphasizing the important role not only of educators but also clinicians
in undergraduate learning on clinical placement. Though the findings reflect age
long problems associated with student learning in the clinical field, it serves
to remind all nurses of the importance they play in the learning process. This
study reflects the importance of effective communication between the health and
education sectors and the need to concentrate on strategies which will strengthen
this bond.
PMID- 10188467
TI - Working to learn and learning to work: placement experience of Project 2000
nursing students in Scotland.
AB - It is evident that the Scottish colleges have designed and provided very
different curricular arrangements to support students' learning to practise in
placements. Evaluation has demonstrated that some of these arrangements are of
fundamental importance in facilitating or constraining the educational experience
of students, including opportunities for reflection on experience, students'
preparation for placements, the role of tutors in students' placement learning,
the preparation of mentors and the utility of instruments for the assessment of
students' practice-based learning. In addition to the formal provision in support
of students' learning to work, students have developed their own informal
strategies in order to meet their (sometimes conflicting) needs to maximize
practical learning opportunities, ease entry into the nursing team and achieve
favourable assessment of learning. Some of these involve working in order to
learn. This paper is based on the work of the National Board-funded Evaluation of
Project 2000 in Scotland (1992-96). The remit of the evaluation was to examine
the teaching/learning processes of the Project 2000 nursing programmes and the
new midwifery programmes, and their relationship to the educational outcomes for
individual students, giving particular emphasis to the experience of students.
PMID- 10188468
TI - Psychology as a theoretical foundation for health education in nursing:
empowerment or social control?
AB - This article explores the relationship between psychology and health education
and illustrates how ostensibly 'neutral' models and theories of psychology can be
used by conflicting health education philosophies and ideologies. We contend both
that health education is an intrinsic element of nursing (which, for the purpose
of this article, also includes health visiting and midwifery) and that psychology
legitimately underpins practice. Our concern in this article is in the potential
application of models and theories of health-related behaviour such as the health
belief model (Rosenstock et al 1988), the theory of reasoned action (Fishbein &
Ajzen 1985) and the stages of change model (Prochaska & DiClemente 1982) to the
health education elements of nursing practice without an awareness and scrutiny
of their particular ideological standpoint, and contrasting relationships to
power, and thus an understanding of the potential ambiguity regarding their role
and function.
PMID- 10188469
TI - Developing a nursing research culture in the university and health sectors in
Western Sydney, Australia.
AB - The context for the development of a research culture in both the health and
education sectors in Australia is similar to that in other developed countries.
Contextual factors, especially those resulting from increasing fiscal constraint,
militate against improved research productivity for nurses in both university and
health sectors. Despite this, however, an impressive range of initiatives have
been designed and introduced, both unisectorally and intersectorally, in the last
14 months to expedite the development of a nursing research culture in Western
Sydney. The former include, in the University of Western Sydney (UWS), reward
systems for research productivity and development, the funding of Designated
Research Groups and Faculty Research Support Units. In the health service they
include the funding of a Clinical Development Unit (Nursing)--CDU(N)--leadership
program and the provision in 1997-98 of seed funds for research projects to be
undertaken in the CDU(N)s. Intersectoral initiatives include the joint funding of
four 'clinical' nursing Chairs, other sub-professorial positions and a 'flagship'
series of nursing research seminars. All these initiatives will be described,
together with an assessment of their impact to date, in terms of (1) research
productivity, (2) improved intersectoral relationships and (3) heightened
visibility and appreciation of nursing and nursing research.
PMID- 10188470
TI - Personal qualities or skills? A report of a study of nursing students' views of
the characteristics of counsellors.
AB - The personal qualities associated with effective counselling have been discussed
in the research and counselling literature. Counselling skills have been proposed
as tools to be learned by student nurses. In this study of 162 students of
nursing, respondents were asked to identify what they felt to be the important
personal qualities of a counsellor. They were asked not to identify their own
skills or qualifications. The findings were broadly in line with those of other
studies in that students felt that qualities such as being non-judgemental,
empathic and understanding were important. A notable finding was that 73% of
respondents identified 'being a good listener' as a personal quality in contrast
to the literature which usually describes listening as a skill. This paper
describes the study, reports the findings, and offers a discussion of the
question of the implications of identifying listening as a personal quality as
well as--or instead of--a skill. The study has implications for the way in which
counselling skills may be taught and how nurse educators might consider the
qualities associated with counselling.
PMID- 10188471
TI - Some thoughts on nurse-education/service partnerships.
AB - This paper discusses some of the issues involved in the design of the processes
for developing effective partnerships between faculties of nursing and nursing
provider organizations. After defining the term 'partnership' it considers,
first, the advantages which can be realized from effective nurse
education/service partnerships. Secondly, it briefly explores how effective
partnerships can be formed while suggesting that these prescriptions do not
guarantee success. Finally, it argues that effective partnerships between nurse
education and service are most likely to be realized when their development is
stated explicitly in the developmental strategy of the organizations involved.
PMID- 10188472
TI - Humour: a phenomenological study within the context of clinical education.
AB - On reflection after a busy day in the ward, undergraduate nursing students
concluded that having a clinical teacher who used humour helped them cope with
their clinical experiences. This encouraged the author to look deeper into what
humour is and describe the lived experiences of nursing students with teachers
who used humour. A phenomenological study was undertaken to explore 48 Australian
undergraduate nursing students' lived experiences of humour as used by their
clinical teachers during clinical education. The data were collected by
interviews. Colaizzi's phenomenological methodology was used to analyse the data.
The results showed that humour makes it easier for the nursing students to cope
with the anxiety-producing situations encountered during their clinical
experiences. According to the results, the majority of nursing students preferred
to be with a clinical teacher with sense of humour to facilitate/supervise them
in the clinical area. However, a word of caution in using humour was revealed in
this study because of the personal nature of this phenomenon. Therefore, this
study is significant in that it provides a deeper understanding of humour as part
of the teaching-learning process within the context of clinical education. The
clinical teacher's use of humour during their encounters with the nursing
students during clinical education is described and implications for nursing
education is discussed.
PMID- 10188473
TI - A clinical career ladder for nursing and more on consultant nurses.
PMID- 10188474
TI - Pressure area risk assessment in intensive care.
AB - Risk assessment tools have been in use for many years now but debate still exists
about their effectiveness Several tools exist that try to meet the specific needs
of intensive care patients Differences can be highlighted between the use of a
general tool (Waterlow, 1995) and an ITU-specific one (Sunderland (Lowery, 1995))
Not all risk assessment tools are suitable for all areas of practice: the most
appropriate one must be selected for each area
PMID- 10188475
TI - A critical reflective analysis of issues surrounding the admission of a patient
to ITU.
AB - John's (1995) Model of Structured Reflection was used to explore and develop
personal and professional knowledge The situation explored acknowledges the
complexities surrounding nursing judgements and decisions Benefits of reflection
are highlighted
PMID- 10188476
TI - Unravelling the ethics of a good decision.
PMID- 10188477
TI - Rhabdomyolysis and acute renal failure in intensive care.
AB - The aetiology and pathophysiology of the complex clinical condition
rhabdomyolysis are outlined here Rhabdomyolysis can be caused by a number of
factors including excessive muscle activity, direct muscle injury, ischaemia and
excesses of temperature Specific nursing care strategies, focusing on the
pathophysiology of the condition, are proposed The priorities of care should
centre on maintaining patient safety with monitoring of cardiovascular and
respiratory systems and assessment of renal function
PMID- 10188478
TI - Sedation scoring in a general ICU--comparative trial of two assessment tools in
clinical practice.
AB - The literature surrounding sedation and assessment tools is reviewed Action
research is used to assess the transferability of two published assessment tools
Recommendations for improving this aspect of patient care are given Areas for
future research are highlighted
PMID- 10188480
TI - Nursing and the virtual world of the next era.
PMID- 10188479
TI - The implications of pulmonary vascular resistance on the nursing care of an
infant with hypoplastic left heart syndrome.
AB - The pathophysiology of pulmonary vascular resistance is described Specific
nursing interventions required to maintain stable haemodynamics are explored The
major implications involved in suctioning infants post Norwood operation for
hypoplastic left heart syndrome are discussed.
PMID- 10188481
TI - The power of care: the Women's Hospital 1884-1914.
AB - The effectiveness of late-nineteenth-century nursing care should not be
underestimated. The archive of patient records at Melbourne's Women's Hospital
reveals a commitment to patient care that more often than not made the difference
between life and death in the recovery from major surgery or post-partum
infection. These records suggest the need to reassess the role of medical care in
the mortality transition after 1850.
PMID- 10188483
TI - An ethic of the fitting: a conceptual framework for nursing practice.
AB - Nurses are expected to act within an ethos of care cognisant of duty, the right,
and the good. Concepts of virtue theory, utilitarianism and deontology are used
to outline a conceptual ethical framework for nurses in practice. This 'Moebius'
framework aims to locate the virtues in a symbiotic relationship with the
principles of utilitarianism and deontology. Under this framework, fitting
ethical responses are sought. Within an ethic of the fitting, rules and
principles do not guarantee the most ethically justifiable outcomes. Within the
Moebius approach, the nurse ought to respond with a sense of compassion that
befits the moment rather than adhere to a rule at all costs.
PMID- 10188482
TI - The human dimension of nosocomial wound infection: a study in liminality.
AB - Nosocomial wound infection is a disease that has to date been primarily
understood through the language of science and biomedicine. This paper reports on
findings from a sociological, interpretive study that focused on the experiential
dimension of this phenomenon. The illness experience of a nosocomial wound
infection is examined within a cultural milieu that values the smooth, untroubled
body and alternatively ascribes cultural meaning to a body that has a definable
illness. Within this context the person with a chronic wound from nosocomial
infection defies normative categorisation and is thus situated outside the
patterning of society. The human dimension of nosocomial wound infection includes
the private, existential and embodied aspects of living with a chronic, infected
wound. This report indicates that the experiential dimension is characterised by
an embodied state of liminality. People with this illness live an indeterminate
existence that is in-between health and illness, cure and disease. As such they
have no recognised place in the medical or social world.
PMID- 10188484
TI - Skin as cover: the discursive effects of 'covering' metaphors on wound care
practices.
AB - This paper outlines a Foucauldian analysis of interactions between nurses and
patients during wound care procedures in a burns unit. It explores the use of
Kristeva's psychoanalytic concepts of abjection and the abject body to illuminate
the emotional affects of wounds on nurse and patient. In this process, I identify
how cultural metaphoric understandings about skin influence and organise the care
of burns patients. Such analysis suggests the import of the complete skin, the
medical scientific control over the definition of this work, and the emotional
forces that resist such control.
PMID- 10188485
TI - Hermeneutic philosophy. Part II: A nursing research example of the hermeneutic
imperative to address forestructures/pre-understandings.
AB - Hermeneutic research requires that pre-understandings are brought to
consciousness in order to provide the phenomenon under investigation with the
greatest opportunity to reveal itself. This hermeneutic imperative is dealt with
in the present study. My research involved explicating the practice knowledge of
nursing on residential adolescent mental health units, and as I had worked on
such units I held pre-understandings that would influence the research. I
addressed pre-understandings in three ways: (i) by developing understandings of
practice knowledge through a hermeneutic conceptualisation of it; (ii) by working
out forestructures of the phenomenon under investigation. Using Heidegger's
writing on forestructures, 20 statements were generated, interpreted and
reconceptualised as my forestructures of residential adolescent mental health
nursing. I used this work to review participant interviews in an effort to
prevent myself from only finding what I already assumed I would find in relation
to practice knowledge; and (iii) by formulating pre-understandings of the
phenomenon of interest. Using Gadamer's writing on reflection, seven stories were
written and interpreted as my pre-understandings of adolescent mental health
nursing practice. I used this work to consider the presence of pre-understandings
during textual interpretation in an attempt to prevent premature interpretive
closure. In these ways, I brought my forestructures/pre-understandings to
consciousness, reflected on them, questioned their origins, adequacy and
legitimacy and thereby took account of their influence on myself and the
research.
PMID- 10188486
TI - The sexual embodiment of the cancer patient.
AB - This paper draws upon data from my doctoral studies and uses poststructuralism as
a methodology to provide a way of seeing and understanding cancer patients'
complex experience of their bodies. Cancer patients were massaged for the purpose
of this study and the themes addressed in this article are linked to the
sexuality of the person being massaged and the masseuse (PVDR). In order to
capture the richness of the cancer patients' experience, the data are presented
in an unconventional way--in the form of poetry. The poems show that the damaged
bodies of cancer patients are still sexual in nature. In this research, the body
of the cancer patient is a discursive one inscribed with power, culture, society
and history. There are also themes of managing the body, altered embodiments of
femininity, altered embodiments of masculinity, intimacy, and speaking the
unspeakable.
PMID- 10188487
TI - Reform in public health: where does it take nursing?
AB - The Australian healthcare system is undergoing changes that are impacting
tangibly on professional nursing practice. While the evidence is clear that the
changes pose a challenge to maintaining standards amidst resource cuts and
restructuring, the processes through which these changes occur and the decisions
which drive the reforms remain complex and largely obscure. This paper intends to
stimulate further thinking and debate among nurses about the effects of these
reforms on the conduct of practice, both in terms of our emerging discipline and
our ability to conduct clinical nursing practice. It offers a way of
understanding the policy 'reform' process through an application of policy
analysis grounded in critical social theory. The discussion sets out to apply
these analytical propositions to specific events that constitute examples of
change in the nursing workplace, and to focus on the implications for nurses and
health service clientele.
PMID- 10188488
TI - 'It comes together at the end': the impact of a one-year subject in Nursing
Inquiry on philosophies of nursing.
AB - This paper reframes an interpretive study as critical inquiry as the researchers
interrogate their roles and authority in the 'reading' of what is valued as
reflective. Working from data collected in written philosophies and interviews
within the context of a one-year subject aimed at developing reflective practice
and an appreciation of ways of knowing, this paper examines the change in
philosophies of nursing perceived by three university-based educators and their
students. The study reveals a growing appreciation of the complexity of nursing
but a limited consideration of the dialectic of critical theorising and everyday
engagement necessary to critical reflection and reconstruction of action. More
importantly, the process of research collaboration raises questions of the soul
searching necessary for university educators to act against the institutionalised
political context that determines what is seen to be of value in student
learning.
PMID- 10188490
TI - Response to marie-francoise colliere: using anthropology to analyse healthcare
situations
PMID- 10188489
TI - Response to Marie-Francoise Colliere: using anthropology to analyse healthcare
situations.
PMID- 10188491
TI - 'Mission impossible': musings on a postgraduate research project.
PMID- 10188492
TI - Logging on to the Net.
PMID- 10188493
TI - Women's health osteopathy: an alternative view.
PMID- 10188494
TI - Quality and standards.
PMID- 10188495
TI - A model service.
PMID- 10188496
TI - NVQs for managers.
PMID- 10188497
TI - Quality of care in nursing homes.
PMID- 10188498
TI - Reforming Scotland. Interview by Tom Keighley.
PMID- 10188499
TI - How to motivate your staff.
PMID- 10188500
TI - Missed opportunities.
PMID- 10188501
TI - Regaining public confidence.
PMID- 10188502
TI - Appropriate staffing: our right, our responsibility.
PMID- 10188503
TI - Uniform patient care: one level or two?
AB - The author clarifies what constitutes the "comparable care," "uniform care," and
"one level/same level care" that the Joint Commission uses to describe uniform
performance of patient-care processes.
PMID- 10188504
TI - Medicare increases managed care's accountability, Part 2.
AB - In Part 1, the author explained Medicare's Quality Improvement System for Managed
Care, Medicare's first consistent set of standards to monitor and evaluate the
quality of managed care for its members. This month, read about the plans' need
to meet certain patient-focused standards and the strain this places on plans'
administrations.
PMID- 10188505
TI - Nursing malpractice: cause for consideration.
AB - Because so many factors influence a patient's health, it's difficult to know with
certainty that a nurse's error actually caused the negative outcome. In nursing
malpractice cases, causation can be a successful defense strategy.
PMID- 10188507
TI - What else can I do to show them they're valuable?
PMID- 10188506
TI - Let's talk telemetry.
AB - As telemetry becomes more prevalent, the lines between medical device and
clinical information system begins to blur. The author explains why telemetry is
growing and merging with traditional information systems and the issues this
creates.
PMID- 10188508
TI - It's a match!
AB - When interviewing a candidate for employment, nurse managers must analyze a
unit's strengths and weaknesses to find someone who not only fits the job
description, but will be an asset to the unit.
PMID- 10188510
TI - Cyber-savvy recruitment.
PMID- 10188509
TI - Become architects of your future.
AB - Here, learn to be stewards of a vision and design the health care infrastructure
so it works for you.
PMID- 10188511
TI - Time to try travel nurses?
PMID- 10188512
TI - Recognize, reward, retain.
AB - Staff recognition plans can be tools for retention or points of contention. The
author shows the do's and don'ts for implementing a successful program on your
unit.
PMID- 10188514
TI - Follow family-focused care principles.
AB - Making the transition from traditional obstetrics care to single-room maternity
care involves changes in the physical facility, cross-education, and new roles.
The most important success factor is the staff's response to the change.
PMID- 10188513
TI - The "new team" triad.
AB - Nurse managers develop new staffing patterns to increase the quality and cost
effectiveness of care. Ongoing evaluation and adjustments to the new patient-care
delivery system are key.
PMID- 10188515
TI - Meeting the challenge of unscheduled outpatient visits.
AB - Cancer patients receive multimodal therapy and treatments on an ongoing basis in
free-standing cancer centers, infusion centers, and oncology offices and at home.
To serve those who require unscheduled evaluation for treatment effects, one
hospital developed a program to receive those visits on an inpatient cancer unit.
PMID- 10188516
TI - Is a nursing shortage on the way?
AB - Managed care, new technology, and treating more patients outside the hospital are
among the factors that can induce a future nursing shortage.
PMID- 10188517
TI - Is cross-training medical/surgical RNs to ICU the answer?
AB - Two nursing units band together to provide ICU support staff by capitalizing on
the education and experience of a core group of medical/surgical RNs.
PMID- 10188518
TI - Custom competencies: developing a unit-specific program.
PMID- 10188519
TI - Hiring official loses top candidates.
PMID- 10188520
TI - Parameters for vital signs monitors.
AB - To purchase the best vital signs monitors for your unit, follow the five steps of
technology assessment--need, safety, effectiveness, economics, and social impact.
PMID- 10188521
TI - About getting the community involved in care management.
AB - Here, two nurse executives explain how to involve community members in care
management.
PMID- 10188522
TI - Making the case for nursing.
PMID- 10188523
TI - Denying care versus denying payment.
AB - Learn how to handle the issues that surround managing the risks of denying care
versus managing the risks of denying payment according to the Consolidated
Omnibus Budget Reconciliation Act of 1986 and its provisions.
PMID- 10188524
TI - Pacemaker interference.
AB - Dispelling myths for patients with pacemakers begins with educating employees
about electromagnetic interference.
PMID- 10188525
TI - How can I create a more collaborative practice environment in the unit?
PMID- 10188526
TI - Questions & answers from the JCAHO. Patient assessment by the book.
AB - The author clarifies requirements for performing, documenting, and authenticating
patients' history and physical.
PMID- 10188527
TI - Examining the dollars and cents of care.
AB - Frontline nurses and nurse managers must understand the economic realities of
their product--care--to manage costs and boost net revenues.
PMID- 10188528
TI - Motivate!
AB - Nurse managers must create a work environment that supports and develops their
staff's and organization's interdependent goals and needs. Fostering effective
communication, accountability, and recognition are necessary to motivate staff.
PMID- 10188529
TI - Ethics of assisted suicide and euthanasia.
AB - Nursing's social contract includes respecting and protecting human life. Issues
surrounding assisted suicide challenge these ethics, not to mention the legal
system.
PMID- 10188530
TI - Testing the limits: shift rotation and the ADA.
AB - A Massachusetts case brought under the Americans with Disabilities Act tests the
validity of shift rotation as an essential job function.
PMID- 10188531
TI - Merge right: market forces and antitrust.
AB - As providers, insurers, and physicians partner for market share, nurse leaders'
responsibilities change. To ensure nursing's bright future, leaders must
understand the corporate, consumer, and legal trends affecting the marketplace.
PMID- 10188532
TI - Putting it together: a clinical documentation system that works.
AB - To save caregivers' time and institutional dollars, designs a clinical
documentation system that integrates data from initial assessment, care planning,
charting, and clinical pathways.
PMID- 10188533
TI - "Closet" incidents.
AB - Learn what constitutes a sentinel event and how to identify possible system
failures.
PMID- 10188534
TI - Improve communication in a shared governance system.
PMID- 10188535
TI - Forging partnerships in care.
PMID- 10188537
TI - When trouble knocks, CIRCLE the wagons.
PMID- 10188536
TI - Six pointers for addressing employee performance concerns.
PMID- 10188538
TI - How to defuse a walking time bomb.
AB - Violence in health care institutions throughout the country is increasing at an
alarming rate. This article will help you and your staff identify the potential
of patients, family, and visitors for becoming violent while they're in your
unit.
PMID- 10188539
TI - Choose a successful clinical information system. A three-step, multidisciplinary
approach.
AB - With so many choices, the process of selecting a successful clinical information
system is complex. Here, review key questions and considerations that can help
your organization make the right choice.
PMID- 10188540
TI - Ask AONE's experts ... about how to negotiate your position after a merger.
PMID- 10188541
TI - [He who smiles, shows dignity].
PMID- 10188542
TI - [Humor and cynicism].
PMID- 10188543
TI - [Friederike Dittrich, 1918-1998].
PMID- 10188544
TI - [The role of the nurses' aide in the team].
PMID- 10188545
TI - [In Carinthia nursing is turning academic--at universities and vocational
schools].
PMID- 10188546
TI - [Vorarlberg: from association to "Institute for Health Care and Nursing"] [In
Process Citation]
PMID- 10188547
TI - [Dialog: physician and nurse on the topic of Bach Flower therapy. Interview by
Wolfgang Fuchs].
PMID- 10188548
TI - [Hedwig Birkner, a pioneer in Austrian nursing].
PMID- 10188549
TI - [International Council of Nurses: cooperation between nursing personnel and
physicians].
PMID- 10188550
TI - [Five theses about humor in nursing].
PMID- 10188552
TI - [Analysis of the situation--conditions for teaching].
PMID- 10188551
TI - [Topic: Healthy work times. A model of work time by Erika Lechner, Director of
Nursing Services at the Kaiserin Elisabeth Hospital].
PMID- 10188553
TI - [Caring for patients with Hickman-Broviac catheters: a case study].
AB - Caring the patient with Hickman-Broviac catheter: a case study. The authors make
a short literature review about the Hickman-Broviac catheter and after they
analyse and comment about the nursing staff's knowledge and patient's self care
related to this catheter.
PMID- 10188554
TI - [Identification of the types of touching during nursing care in an outpatient
service].
AB - This study was realized in the outpatient ward of bone marrow transplantation.
The sample consisted of 17 adult patients and six workers. The data was collected
from October to December, 1996, being obtained through filming, decodification of
the films, a questionnaire and interview with the workers. The purposes were to
identify in what situations the different types occurred, and which regions of
the body were involved. It was found that most of the touching was of the
instrumental type. The regions touched were the thorax and upper limbs.
PMID- 10188555
TI - [Identification of psychosocial problems in patients with Hansen's disease by
analysis of computerized resources].
AB - The purpose of this study was to identify leprosy patients' psychosocial problems
experienced after they were informed about their diagnosis. We focused attention
upon concerns and behavioral changes related to their families, friends, jobs and
to themselves. Data were obtained by a two opened questions interview and they
were analysed with the aid of artificial intelligence techniques. These
intelligence tools were used to discover the most frequent words, phrases and
concepts existing in the interview reports. The results showed that after being
informed about their diagnosis, the majority of the patients referred some
concerns and behavioral changes related to their families, friends, jobs and to
themselves. The main concerns of the population were related to the disease
(transmission, the treatment extension, the possibility of hospitalization, the
uncertainty about the cure). These facts induced some of the patients to avoid
telling people about the disease they have.
PMID- 10188556
TI - [Basic orientation of nurses for the administration of psychotropic drugs].
AB - With this study the authors want to furnish the nurses with one more reference
source to guide their actions in caring for the patient that use psychopharmaco.
It is described the pharmacological groups and considerations are made about the
care with patients that are using them.
PMID- 10188557
TI - [Public health service: what women say].
AB - The way poor women, who live in a given reality, perceive institutional policies
of the health sector and face them is the object of reflection presented in this
study. As category of analysis, the authors make use of social representation,
understood as share of the contradictory social relations and of the individual
and collective history of the groups, Authors discuss the inequities in public
health care, focusing the way popular segments reaffirm and deny dominant
knowledge and practices. Their speech about in the health attention showed, at
the same time, absorption/reproduction of the rules spread by "official" medical
system and the incorporation/translation of their necessities, experiences and
specifics interests.
PMID- 10188558
TI - [Metal worker's perception of health problems and environmental risks at the work
place].
AB - Research was carried out in Osasco, Greater Sao Paulo, to know the main health
problems perceived by metalworkers' at their workplace and the need actions to
prevent it or minimize them. With this objective in mind, 452 workers were
interviewed at a metallurgic industry by means of a questionnaire in which they
were asked first to mention five health problems perceived at the workplace, and
then to select the most important one. They were also asked what they thought
managers, supervisors and workers could do to avoid or minimize the main risk
each worker had selected. According to their answer, although the chemical risk
was the most frequently mentioned, the suggestions to actions to be implemented
by supervisors and managers were related to psycho-social factors, that is, human
problems of administration and organizational behavior.
PMID- 10188559
TI - [Project of integral rehabilitation of undernourished children. A proposal for
nursing. Case report].
AB - The authors present a case report of nutrition recuperation in an undernourished
child involved in the Integral Recuperation of Undernourished Children Project at
the University Hospital in Campo Grande, Mato Grosso do Sul, Brazil. They show
the importance of nursing assistance as a member of multiprofessional team in
projects of this matter.
PMID- 10188560
TI - [Perception of reality within a hospital situation and its effect on
interpersonal communication].
AB - The present study focuses on perception as na integral part of the communication
process and emphasizes, when consciously accomplished, its occurrence as an
interactive facilitator agent likely to widen the understanding of interpersonal
relationships.
PMID- 10188561
TI - [The nursing team and occupational accidents with potentially contaminated
material in the era of HIV].
AB - This investigation was carried out in order to: identify the occurrence of
professional accidents with perforate cutting potentially contaminated material
among nurses and nursing auxiliaries that work in a general teaching hospital in
the interior of the state of Sao Paulo. The other objectives were: to associate
the occurrence of accident with the professional category and period of work; to
identify the type of perforate cutting material most involved in accidents, to
identify the attitudes taken by the person accidented. The data were collected on
individual interview based on a structured formulary in which the following
information was registered: the probable reason of accident, how long the
professional has been working on such function, the material involved in the
accident, the actions taken after the accident. It was evidenced that the
Standard Precautions or the Universal Precautions as they used used to be
nominated are not being used as they should be. Such attitude brings risks to the
nursing team. We think that this team needs specific orientations through
continuing education concerning the theme.
PMID- 10188562
TI - [The planning process in nursing in a teaching hospital].
AB - The aim of this research was to identify the theoretical methodological model
that are basing the development of the management function in planning, according
the nursing practices, in the School Hospital of the University of Sao Paulo.
Based on the results the nurses emphasized the importance of introducing the
reference of planning strategies in the practice in order to make changes.
PMID- 10188563
TI - [League against pain: an experiment in extracurricular teaching].
AB - Although anatomical and physiological base of pain are subject of the basic
sciences in health undergraduate curriculum, it is not usually to have pain
concepts and therapy into undergraduate programs. Describing the League Against
Pain objectives and organization and the students' opinions about their
participation in this league were the aim of this study. The League Against Pain
Statute was consulted to describe its objectives and organization. The opinions
of all of the students that attended the League Against Pain program in 1995 and
1996 were investigated. The League Against Pain was organized at an university
hospital in 1995. It is composed by nurses and medical students and professionals
(physicians in varied specialties and nurses). All the activities are voluntary
and the students are the managers of the League. The objectives of the League
are: improving the quality of teaching of pain subjects in nursing and medical
schools; developing research in epidemiological, clinical and therapeutics
aspects of pain and to promote a model of multidisciplinary and multiprofessional
assistance. The most frequent students' opinions about their participation in the
League were: their abilities in pain control and in professional and client
relationship were improved; they achieved their objectives; that pain should be
included into undergraduate courses; and they would recommend the League for
other students. The results are promising. The students' opinions about their
experience in the League Against Pain have showed that the League Against Pain
could be an usefull model to introduce pain subjects to undergraduate nursing and
medical students.
PMID- 10188564
TI - [Young and old ... the same fight].
PMID- 10188565
TI - [Diabetes in the elderly].
PMID- 10188566
TI - [How to treat agitation in the elderly].
PMID- 10188567
TI - [The right thing to do in case of an ophthalmological problem].
PMID- 10188568
TI - [Vitamins B, C and beta carotene].
PMID- 10188569
TI - [A form for the contact between old age home and emergency unit. An instrument
for the improvement of elderly care].
PMID- 10188570
TI - [Music and the elderly].
PMID- 10188571
TI - [Ethics and the elderly].
PMID- 10188572
TI - [Walking at home. How to limit the risk of a fall].
PMID- 10188573
TI - [Hospital infections. How to improve permanently the level of hygiene in
geriatric units].
PMID- 10188574
TI - [Social malaise, discomfort of adolescents].
PMID- 10188575
TI - [A consultation for adolescents. Between body and mind].
PMID- 10188576
TI - [The older adolescent and the hospital. Inexistent legal regulations for an
everyday hospital reality].
PMID- 10188577
TI - [Adolescents in follow-up care and in rehabilitation centers. Social services].
PMID- 10188578
TI - [Adolescent clothing].
PMID- 10188579
TI - [A place for health for adolescents. Listening in order to prevent].
PMID- 10188580
TI - [Children, health, and us...].
PMID- 10188581
TI - [When the child appears ... abnormal].
PMID- 10188582
TI - Light perception in higher plants.
AB - Photosynthetic plants depend on sunlight as their energy source. Thus, they need
to detect the intensity, quality and direction of this critical environmental
factor and to respond properly by optimizing their growth and development.
Perception of light is accomplished by several photoreceptors including
phytochromes, blue/ultraviolet (UV)-A and UV-B light photoreceptors. In recent
years, genetic, molecular genetic and cell biological approaches have
significantly increased our knowledge about the structure and function of the
photoreceptors, and allowed the identification of several light signal
transduction components. Furthermore, this research led to fruitful interaction
between different disciplines, such as molecular biology and ecology. It is safe
to assume that we can expect more milestones in this research field in the
upcoming years.
PMID- 10188583
TI - MAP kinases in plant signal transduction.
AB - Mitogen-activated protein kinase (MAPK) pathways are modules involved in the
transduction of extracellular signals to intracellular targets in all eukaryotes.
Distinct MAPK pathways are regulated by different extracellular stimuli and are
implicated in a wide variety of biological processes. In plants there is evidence
for MAPKs playing a role in the signaling of abiotic stresses, pathogens and
plant hormones. The large number and divergence of plant MAPKs indicates that
this ancient mechanism of bioinformatics is extensively used in plants and may
provide a new molecular handle on old questions.
PMID- 10188584
TI - GTP-binding proteins in plants.
AB - GTP-binding proteins are found in all organisms. They are important switches that
cycle between an active and an inactive state, ensuring vectorial flow of
information on the expense of guanosine triphosphate (GTP). In this review, we
discuss current progress in the molecular characterization and functional
analysis of plant genes encoding heterotrimeric and small GTPases. An up-to-date
list including all cloned plant GTPase genes is given and a systematic
classification is proposed.
PMID- 10188585
TI - G proteins as drug targets.
AB - The structure and function of heterotrimeric G protein subunits is known in
considerable detail. Upon stimulation of a heptahelical receptor by the
appropriate agonists, the cognate G proteins undergo a cycle of activation and
deactivation; the alpha-subunits and the beta gamma-dimers interact sequentially
with several reaction partners (receptor, guanine nucleotides and effectors as
well as regulatory proteins) by exposing appropriate binding sites. For most of
these domains, low molecular weight ligands have been identified that either
activate or inhibit signal transduction. These ligands include short peptides
derived from receptors, G protein subunits and effectors, mastoparan and related
insect venoms, modified guanine nucleotides, suramin analogues and amphiphilic
cations. Because compounds that act on G proteins may be endowed with new forms
of selectivity, we propose that G protein subunits may therefore be considered as
potential drug targets.
PMID- 10188586
TI - Structure, function and evolution of antifreeze proteins.
AB - Antifreeze proteins bind to ice crystals and modify their growth. These proteins
show great diversity in structure, and they have been found in a variety of
organisms. The ice-binding mechanisms of antifreeze proteins are not completely
understood. Recent findings on the evolution of antifreeze proteins and on their
structures and mechanisms of action have provided new understanding of these
proteins in different contexts. The purpose of this review is to present the
developments in contrasting research areas and unite them in order to gain
further insight into the structure and function of the antifreeze proteins.
PMID- 10188587
TI - The cdk-activating kinase (CAK): from yeast to mammals.
AB - Cell cycle progression is regulated by cyclin-dependent kinases (cdks). The
activity of cdks is tightly controlled by several mechanisms, including binding
of subunits to cdks (cyclins and inhibitors), and phosphorylation events. This
review focuses on the activating phosphorylation of cdks by an enzyme termed cdk
activating kinase (CAK). Two classes of CAKs have been identified: monomeric
Cak1p from budding yeast and the p40MO15 (cdk7)/cyclin H/MAT1 complex from
vertebrates. Cak1p is the physiological CAK in budding yeast and localizes to the
cytoplasm. p40MO15(cdk7)/cyclin H/MAT1 localizes to the nucleus, is a subunit of
the general transcription factor IIH and activates cdks as well as phosphorylates
several components of the transcriptional machinery. Functions, substrate
specificities, regulation, localization, effects on cdk structure and involvement
in transcription are compared for Cak1p and p40MO15(cdk7).
PMID- 10188588
TI - Nuclear translocation of Fos is stimulated by interaction with Jun through the
leucine zipper.
AB - Jun and Fos, b-ZIP transcription factors, form a heterodimer and bind to DNA
enhancer elements, thereby regulating the expression of target genes. The present
study was undertaken to investigate the molecular mechanism underlying nuclear
translocation of the Jun/Fos complex. For this purpose, normal rat kidney cells
were microinjected with a DNA expression vector containing wild-type or mutant c-
or v-jun together with c- or v-fos, followed by detection of the subcellular
localization of Jun or Fos by immunofluorescence staining. The nuclear
accumulation of Fos was markedly enhanced by the presence of wildtype Jun, but
not by Jun mutants lacking nuclear targeting or zipper dimerization functions,
implying that Jun and Fos mutually interact via their leucine zippers and
translocate from the cytoplasm to the nucleus using the markedly stronger nuclear
localization signal of Jun.
PMID- 10188589
TI - Long-term changes in tyrosine phosphorylation of the abundant nuclear proteins
during granulocytic differentiation of HL-60 cells.
AB - The two-dimensional electrophoretic patterns of nuclear proteins and their
tyrosine phosphorylation were compared for HL-60 cells before and after
differentiation induction to granulocytes by dimethyl sulfoxide, all-trans
retinoic acid and N6,O2-dibutyryl adenosine 3':5'-cyclic monophosphate.
Regardless of the inducer used, some nuclear proteins, which are tyrosine
phosphorylated in proliferating HL-60 cells, undergo gradual dephosphorylation 12
72 h after induction of differentiation, followed by drastic dephosphorylation
during maturation to granulocytes. At least 13 nuclear proteins with a molecular
mass of 35-110 kDa are dephosphorylated, and 6 nuclear proteins undergo tyrosine
phosphorylation. Analysis of the nuclear proteins differentially extracted by
salt and detergents indicates that changes in their tyrosine phosphorylation
during the maturation stage of differentiating granulocytes occur mainly in
proteins which are abundant in nucleoplasm, chromatin and residual nuclear
structures. The abundance of these proteins, residing in the nuclear structures,
and their long-term modification in phosphorylation during the maturation stages
of differentiation strongly suggest that tyrosine phosphorylation of these
proteins is involved in reorganization of the differentiating cell nucleus.
PMID- 10188590
TI - Sex- and age-related differences in ceramide dihexosides of primary human brain
tumors.
AB - Neutral glycolipids (NGL) are promising diagnostic markers of human gliomas, but
differences in NGL with age and sex have not been examined. Previous work
demonstrated that ceramide dihexosides (CDH) levels in mouse kidney are age- and
sex-dependent, probably due to levels of sex hormones. We quantitated CDH in 181
human gliomas and found significant differences with sex and age, particularly
menopause and male puberty. This emphasizes the importance of assessing results
of studies on glycolipids in disease states with respect to age and sex in order
to avoid erroneous conclusions concerning the relationship of glycolipid
composition with diagnosis and pathogenesis.
PMID- 10188592
TI - Abnormal serum lysophospholipids in multiple myeloma patients.
AB - Lysophosphatidylcholine (LPC) and lysophosphatidic acid (LPA) mediate various
kinds of biological activities and play an important role in cellular signal
transduction. We analyzed serum phospholipids obtained from 16 multiple myeloma
(MM) patients and observed that serum LPA level was significantly higher in MM
patients (5.3 +/- 0.5 nmol/mL) than in normal controls (1.7 +/- 0.3 nmol/mL). LPC
level was also higher than that in normal controls, and it correlated
significantly with the concentration of LPA (r = 0.678, P < 0.01). In MM
patients, palmitic acid/linoleic acid ratios in phosphatidylcholine and LPC were
higher than those in normal controls. In the 12-mon follow-up study of two
patients with the immune globulin G type, we recognized that the increase of LPC,
LPA, and arachidonic acid/linoleic acid ratio in phosphatidylinositol
corresponded with a decline in the serum albumin level and choline esterase
activity.
PMID- 10188593
TI - Differential effect of N-ethyl maleimide on delta6-desaturase activity in human
fetal liver toward fatty acids of the n-6 and n-3 series.
AB - The effect of N-ethyl-maleimide (NEM) on delta5- and delta6-desaturase activities
and the incorporation of substrates and products into different microsomal lipid
classes and phospholipid (PL) subclasses were studied in human fetal liver
microsomes, obtained after legally approved therapeutic abortion. Desaturase
activities were measured by a radiochemical method using reversed-phase high
performance liquid chromatography (HPLC). After nonphospholipid (NPL) and PL
separation on silica cartridges, the radioactivity in different lipids of the NPL
group was assessed by two-dimensional thin-layer chromatography, and their fatty
acid (FA) composition by gas-liquid chromatography. The PL subclasses were
separated, and the distribution of radioactivity between products and substrates
was determined in PL subclasses. NEM inhibited the delta5- and delta6-desaturase
activities in the n-6 series of FA but not the delta6-desaturase activity in the
n-3 series, which suggests the existence of two distinct delta6-desaturases, one
for the n-6 series and another for the n-3 series. Whether NEM was present or
absent, most of the radioactivity was recovered in the free FA form (about 80%).
The desaturation products, obtained in the presence or absence of NEM, were
preferentially incorporated into PL, suggesting a channeling of the newly
synthesized FA toward microsomal PL. The comparison of the distribution of
substrates and products incorporated into the different PL classes showed that
most of the labeled FA were incorporated into phosphatidylcholine and to a lesser
degree into phosphatidylethanolamine.
PMID- 10188591
TI - n-3 and n-6 fatty acid enrichment by dietary fish oil and phospholipid sources in
brain cortical areas and nonneural tissues of formula-fed piglets.
AB - Sufficient availability of both n-3 and n-6 long-chain polyunsaturated fatty
acids (LCPUFA) is required for optimal structural and functional development in
infancy. The question has been raised as to whether infant formulae would benefit
from enrichment with 20 and 22 carbon fatty acids. To address this issue, we
determined the effect of fish oil and phospholipid (LCPUFA) sources on the fatty
acid composition of brain cortical areas and nonneural tissues of newborn piglets
fed artificially for 2 wk. They were fed sow milk, a control formula, or the
formula enriched with n-3 fatty acids from a low-20:5n-3 fish oil added at a high
or a low concentration, or the formula enriched with n-3 and n-6 fatty acids from
either egg yolk- or pig brain-phospholipids. Both the fish oil- and the
phospholipid-enriched formula produced significantly higher plasma phospholipid
22:6n-3 concentrations than did the control formula. The 22:6n-3 levels in the
brain, hepatic, and intestinal phospholipids were significantly correlated with
plasma values, whereas cardiac 22:6n-3 content appeared to follow a saturable
dose-response. Feeding sow milk resulted in a much higher 20:4n-6 content in
nonneural tissues than did feeding formula. Supplementation with egg phospholipid
increased the 20:4n-6 content in the heart, red blood cells, plasma, and
intestine in comparison to the control formula, while pig brain phospholipids
exerted this effect in the heart only. The addition of 4.5% fish oil in the
formula was associated with a decline in 20:4n-6 in the cortex, cerebellum,
heart, liver, and plasma phospholipids, whereas using this source at 1.5% limited
the decline to the cerebellum, liver, and plasma. Whatever the dietary treatment,
the phosphatidylethanolamine 20:4n-6 level was 10-20% higher in the brain
temporal lobe than in the parietal, frontal, and occipital lobes in the temporal
lobe by administering the formula enriched with egg or brain phospholipids. In
conclusion, feeding egg phospholipids to neonatal pigs increased both the 22:6n-3
content in the brain and the 20:4n-6 content in the temporal lobe cortex. This
source also increased the 22:6n-3 levels in nonneural tissues with only minor
alterations of 20:4n-6. These data support the notion that infant formulae should
be supplemented with both 22:6n-3 and 20:4n-6 rather than with 22:6n-3 alone.
PMID- 10188594
TI - Dietary alpha-linolenate suppresses endotoxin-induced platelet-activating factor
production in rat kidney.
AB - In comparison with dietary high-linoleate safflower oil, high alpha-linolenate
perilla oil decreased alkylacyl- and alkenylacyl-glycerophosphocholine (GPC)
content in rat kidney by roughly 30 and 25%, respectively. The fatty acid
composition was also modified by high alpha-linolenate oil; arachidonic acid (AA)
level in alkylacyl-GPC, a platelet-activating factor (PAF) precursor, decreased
by 30% along with concomitant increases in the n-3 fatty acid levels. PAF
contents under resting conditions were similarly low in the two dietary groups.
Fifteen minutes after endotoxin administration, PAF and lyso-PAF contents
increased significantly, and the PAF content in the high alpha-linolenate group
was 60% lower than in the high linoleate group; the lyso-PAF contents also tended
to be lower. Lyso-PAF acetyltransferase and CoA-independent transacylase
activities in kidney microsomes increased significantly after endotoxin
administration, while PAF acetylhydrolase activity in the cytosol was relatively
unchanged. The lyso-PAF acetyltransferase and PAF acetylhydrolase activities did
not differ between the two dietary groups, but the CoA-independent transacylase
activity was roughly 30% lower in the high alpha-linolenate group. In agreement
with in vitro study, our present study demonstrates that dietary high alpha
linolenate suppresses PAF production in rat kidney during systemic endotoxemia,
and which is mainly due to the decrease in alkylacyl-GPC content, altered fatty
acid compositions of the precursor lipids and lower CoA-independent transacylase
activity.
PMID- 10188595
TI - Effects of Pinus pinaster and Pinus koraiensis seed oil supplementation on
lipoprotein metabolism in the rat.
AB - The aim of the present study was to assess the effect of vegetal oils obtained
from Pinus pinaster and P. koraiensis seeds on plasma lipoprotein levels and
apolipoprotein (apo) gene expression in rats. These oils contain two particular
fatty acids of the delta5-unsaturated polymethylene-interrupted fatty acid
(delta5-UPIFA) family: all-cis-5,9,12-1 8:3 (pinolenic) and/or all-cis-5,11,14
20:3 (sciadonic) acids. Rats were fed for 28 d a diet containing 5% (w/w) oil
supplement. Two control diets were prepared to match the fatty acid composition
of P. pinaster or P. koraiensis oils with the exception of delta5-UPIFA, which
were replaced by oleic acid. Pinus pinaster seed oil decreased serum
triglycerides by 30% (P < 0.02), very low density lipoprotein (VLDL)
triglycerides by 40% (P < 0.01), and VLDL-cholesterol by 33% (P < 0.03). Pinus
koraiensis seed oil decreased serum triglycerides by 16% [not statistically
significant (ns)] and VLDL-triglycerides by 21% (ns). Gel permeation
chromatography and nondenaturating polyacrylamide gel electrophoresis showed a
tendency of high density lipoprotein to shift toward larger particles in pine
seed oil-supplemented rats. Finally, P. pinaster seed oil treatment was
associated with a small decrease of liver apoC-III (P < 0.02) but not in apoE,
apoA-I, or apoA-II mRNA levels. The levels of circulating apo were not affected
by pine seed oil supplementation. In conclusion, P. pinaster seed oil has a
triglyceride-lowering effect in rats, an effect that is due to a reduction in
circulating VLDL.
PMID- 10188596
TI - Differences in the sterol composition of dominant Antarctic zooplankton.
AB - The composition of free sterols was determined in Antarctic zooplankton species
with various feeding behaviors. In the Southern Ocean, the dominant calanoid
copepods Calanoides acutus, Calanus propinquus, Metridia gerlachei, and Euchaeta
antarctica were investigated during different seasons and compared with the
euphausiids Euphausia superba, E. crystallorophias, and Thysanoessa macrura. In
addition, the Arctic copepods Calanus hyperboreus, C. glacialis, and C.
finmarchicus were studied for comparison. Analyses were performed using gas
chromatography and mass spectrometry. The zooplankton species exhibited a simple
sterol content of up to six sterols. In the copepods, cholest-5-en-3beta-ol (22.1
to 60.5%, range of sample means), cholesta-5,24-dien-3beta-ol (22.3 to 45.2%),
and cholesta-5,22E-dien-3beta-ol (4.3 to 33.4%) contributed most, while in
euphausiids the sterol composition was less complex with cholest-5-en-3beta-ol
always accounting for more than 75% of the total. Although sterols are membrane
constituents and are expected not to vary considerably, differences in the
abundance of sterols were observed between the species and the seasons. In
herbivorous copepods, cholesta-5,24-dien-3beta-ol increased by a factor of 1.5 to
about 45% during the main feeding period in summer; this sterol is a metabolic
precursor of cholest-5-en-3beta-ol in the process of the dealkylation of dietary
C-24 alkylated phytosterols. Cholest-5-en-3beta-ol decreased by the same
proportion. Omnivorous and carnivorous copepods showed average levels of cholesta
5,24-dien-3beta-ol below 25%. These changes in sterol composition between copepod
species seem to reflect their different feeding modes.
PMID- 10188597
TI - Mitochondrial membrane composition of two Arctic marine bivalve mollusks,
Serripes groenlandicus and Mya truncata.
AB - The phospholipid and fatty acid composition of gill mitochondria membranes from
two Arctic marine bivalve mollusks, Mya truncata and Serripes groenlandicus, were
examined. These animals were collected from the Arctic Ocean, where waters remain
below 0 degrees C throughout the year. In both species, the primary membrane
phospholipids were phosphatidylcholine, and phosphatidylethanolamine. Although a
low ratio of bilayer-stabilizing phospholipids to bilayer-destabilizing
phospholipids is frequently associated with cold acclimation in temperate
species, this ratio is very different between the two species. The
monounsaturated fatty acid 20:1 was abundant in the membranes of both Arctic
species equaling 13.0% of the fatty acid composition in S. groenlandicus, and
17.7% in M. truncata. Polyunsaturated fatty acids were relatively low in the
Arctic species, equaling 35.9% of total membrane fatty acids compared to that of
temperate zone mollusks. It is suggested that monoenes are common in the tissues
of Arctic species since they play a role in maintaining membrane function at
subzero temperatures.
PMID- 10188598
TI - Influences of subzero thermal acclimation on mitochondrial membrane composition
of temperate zone marine bivalve mollusks.
AB - The phospholipid and phospholipid fatty acid composition of gill mitochondrial
membranes from two temperate zone marine bivalve mollusks, the quahog, Mercenaria
mercenaria, and the American oyster, Crassostrea virginica, were examined after
acclimation to 12 and -1 degree C. Cardiolipin (CL) was the only phospholipid
with proportions altered upon acclimation to -1 degree C, increasing 188% in the
mitochondrial membranes of M. mercenaria. Although the ratio of bilayer
stabilizing to destabilizing lipids is frequently associated with cold
acclimation in ectothermic species, no change was found in this ratio in either
of the species. Polyunsaturated fatty acids (PUFA) were found only to increase in
C. virginica with cold acclimation, with total n-3 PUFA increasing in the
phospholipid phosphatidylethanolamine, total n-6 PUFA increasing in CL, and total
PUFA increasing in phosphatidylinositol. Monounsaturated fatty acids, not PUFA,
were found to have increased in M. mercenaria, with 18:1 n-9 increasing by 150%
in CL, and 20:1 increasing in both CL and phosphatidylcholine, by 146 and 192%,
respectively. These manipulations of membrane phospholipid and fatty acid
composition may represent an attempt by these species to help maintain membrane
function at low temperatures.
PMID- 10188599
TI - Biosynthesis and localization of phosphatidyl-scyllo-inositol in barley aleurone
cells.
AB - A novel isomer of phosphatidylinositol (PI), phosphatidyl-scyllo-inositol, was
characterized in the aleurone cells of barley seeds. In this investigation, the
subcellular localization of scyllo-PI and the relative rates of biosynthesis and
accumulation of [32P]phosphoric acid ([32Pi])-labeled scyllo- and myo
phosphoinositides in the plasma membrane and intracellular membrane pools were
investigated. About 25% of the [32Pi]-labeled phospholipids were present in
plasma membrane and 75% in intracellular membranes. Incorporation of [32Pi] into
scyllo-PI was greater than into myo-PI in both the plasma membranes and
intracellular membranes at all time points investigated, thus suggesting a higher
rate of biosynthesis; however, the data do not preclude reduced breakdown of
labeled scyllo-PI as a contributing factor. In vitro studies were conducted to
investigate the presence of cytidinediphosphate diacylglycerol (CDP-DG):scyllo
inositol 3-phosphatidyltransferase (scyllo-PI synthase) and to optimize enzymatic
activity. The inclusion of nonionic detergents (Brij 58 and Triton X-100)
effected significant enhancement in the biosynthesis of scyllo-PI, whereas
anionic, cationic, and zwitterionic detergents had little or no effect. This is
the first evidence for CDP-DG:scyllo-inositol 3-phosphatidyltransferase activity.
PMID- 10188600
TI - The isolation and characterization of right-side-out plasma membrane vesicles
from barley aleurone cells.
AB - Examination of organelle- and membrane-specific processes such as signal
transduction necessitates the use of plasma membrane vesicles with cytoplasmic
side-in orientation. We are interested in the structural identity and subcellular
localization of in vivo [32P]phosphoric acid ([32Pi])-labeled phosphoinositides,
including the recently discovered phosphatidyl-scyllo-inositol, for signal
transduction studies. In the first part of this investigation, plasma membrane
vesicles from barley aleurone cells were isolated employing the aqueous polymer
(Dextran and polyethylene glycol) two-phase partition method. The membrane
vesicles that partitioned into the upper and lower phases of the aqueous polymer
two-phase system were characterized and the purity of the vesicles ascertained by
assaying for two marker enzymes, K+-stimulated, Mg2+-dependent adenosine
triphosphatase (EC 3.6.1.3, ATPase), localized in the plasma membranes, and
cytochrome c oxidase, localized in the mitochondria. Inhibitors for ATPases such
as azide, molybdate, and vanadate were used to distinguish between plasma
membrane-associated and intracellular membrane-associated ATPases. These
inhibitor studies suggest that the plasma membrane preparation contained about 7%
of intracellular membrane vesicles and the intracellular membrane fraction
contained about 6% of plasma membrane vesicles. Orientation of the plasma
membrane vesicles was ascertained by measuring the latent ATPase activity. These
latency studies suggest that about 95% of the plasma membrane vesicles were of
cytoplasmic side-in orientation. In the second part of this investigation,
intracellular distribution and in vivo [32Pi] labeling of phosphoinositides in
the plasma membranes and intracellular membranes were investigated. Preferential
accumulation of [32Pi]-labeled phosphatidyl-myo-inositol monophosphate (myo-PIP)
and phosphatidyl-myo-inositol bisphosphate (myo-PIP2) was observed in the plasma
membrane. However, scyllo-phosphatidylinositol (scyllo-PI) was detected in both
the plasma membrane and the intracellular membranes. The cellular concentration
of myo-phosphoinositides was determined, and, after 24 h of labeling with [32Pi],
the ratio of radiolabel in myo-PI, PIP, and PIP2 paralleled the relative
concentrations in aleurone cells.
PMID- 10188601
TI - Principal component analysis of measured quantities during degradation of
hydroperoxides in oxidized vegetable oils.
AB - Decomposition of hydroperoxides in sunflower oil under strictly oxygen-free
conditions was followed by measuring peroxide values against time, absorbance
values at 232 and 268 nm, para-anisidine values, and by quantitative analyses of
volatile products using various additives. The results were arranged in a matrix
form and subjected to principal component analysis. Three principal components
explained 89-97% of the total variance in the data. The measured quantities and
the effect of additives were closely related. Characteristic plots showed
similarities among the measured quantities (loading plots) and among the
additives (score plots). Initial decomposition rate of hydroperoxides and the
amount of volatile products formed were similar to each other. The outliers, the
absorbance values, were similar to each other but carried independent information
from the other quantities. Para-anisidine value (PAV) was a unique parameter.
Since PAV behaved differently during the course of hydroperoxide degradation, it
served as a kinetic indicator. Most additives were similar in their effects on
the mentioned quantities, but two outliers were also observed. Rotation of the
principal component axes did not change the dominant patterns observed. The
investigations clearly showed which variables were worth measuring to evaluate
different additives.
PMID- 10188602
TI - Guidance-based quantification of arm impairment following brain injury: a pilot
study.
AB - This paper reports the design and preliminary testing of a device for evaluating
arm impairment after brain injury. The assisted rehabilitation and measurement
(ARM) Guide is capable of mechanically guiding reaching and retrieval movements
across the workspace and of measuring constraint forces and range of motion
during guidance. We tested the device on four hemiplegic brain-injured
individuals and four unimpaired control subjects. During guided movement, the
brain-injured subjects generated distinct spatial patterns of constraint force
with their impaired arms that were consistent with the standard flexion and
extension "synergies" described in the clinical literature. In addition, the
impaired arms exhibited well-defined workspace deficits as measured by the ARM
Guide. These results suggest that constraint force and range of motion
measurements during mechanically guided movement may prove useful for precise
monitoring of arm impairment and of the effects of treatment techniques targeted
at abnormal synergies and workspace deficits.
PMID- 10188603
TI - An approach to a muscle model with a stimulus frequency-force relationship for
FES applications.
AB - A simplified model of electrically stimulated muscle for use in applications of
functional electrical stimulation (FES) is discussed in this paper. The muscle
model was required to have both stimulus frequency and stimulus intensity
(amplitude/width) inputs. The stimulus frequency versus force relationship of
rabbit muscle was modeled first with a small number of model parameters that
could be identified by simple experiments in a short time. The model identified
was found to be applicable to human muscles. The frequency-force relationships of
electrically stimulated fast and slow type muscles were also predicted by the
model. The frequency-force model and a simplified model of muscle activation
dynamics were used to construct a muscle model that described the summation of
muscle contraction. The use of this model decreased the time burden on patients
during parameter identification at the clinical site. The clinical applicability
of these new model descriptions was suggested through computer simulations.
PMID- 10188604
TI - The function of the finger intrinsic muscles in response to electrical
stimulation.
AB - The actions of the dorsal interosseous, volar interosseous, and lumbrical muscles
were investigated using applied electrical stimulation and recording the moments
that were generated across the metacarpophalangeal joint in flexion/extension and
abduction/adduction, the proximal interphalangeal joint in flexion/extension, and
the distal interphalangeal joint in flexion/extension. These measurements were
made isometrically at various joint angles and levels of stimulation with both
able bodied subjects and persons who had sustained tetraplegia. It was determined
that the dorsal interossei, including the first, were strong abductors of the
fingers and generated a significant moment in metacarpophalangeal (MP) joint
flexion and interphalangeal (IP) joint extension. The volar interossei were the
primary adductors of the fingers, as well as providing a significant moment in MP
joint flexion and IP joint extension. The lumbrical muscles were found to be MP
joint flexors and IP joint extensors, although the moments that were generated
were on average 70% lower than the interossei. The role of the lumbricals as
finger abductors or adductors could not be determined from the data. This
information on the actions and moment generating capabilities of the intrinsic
muscles led to the incorporation of the interossei into electrically induced hand
grasp provided by an implanted neuroprosthesis. The evaluation of the intrinsic
muscles in the neuroprosthesis was accomplished by recording the moment
generating capabilities of these muscles across each of the joints of the finger.
These muscles were capable of generating moments that were 80-90% of the average
attained by the able bodied subjects, and have provided a substantial improvement
to the electrically induced hand grasp.
PMID- 10188605
TI - A study of shoulder motions as a control source for adolescents with C4 level
SCI.
AB - This study quantitatively examined and compared the shoulder motions of C4 level
spinal cord injury (SCI), C5 level SCI, and able-bodied persons as a command
source. The study was motivated by both the success of shoulder control in
functional electrical stimulation (FES) systems designed for C5 level SCI people
and the lack of quantitative information on the shoulder motion of persons with
C4 level SCI. A dual-axis transducer was used to monitor the elevation/depression
and protraction/retraction angles of each subject's shoulder while they performed
three experimental sections which examined: the range of active shoulder motion;
the ability to move incrementally to discrete positions with the aid of visual
feedback; and the ability to hold discrete shoulder positions for an extended
period without visual feedback. Results indicated that each group had the largest
average shoulder displacements (abled = 23 degrees +/- 4 degrees, C5's = 14
degrees +/- 3 degrees, and C4's = 9 degrees +/- 3 degrees) while attempting to
elevate and that on average the C4 group had the smallest range of active
shoulder motion. No statistically significant differences between the groups were
found in either the accuracy or stability of reaching discrete positions with the
aid of visual feedback or in the accuracy of holding discrete shoulder positions
for an extended period without visual feedback. The results suggest that within
their limited range of motion the individuals with C4 level SCI retained shoulder
control sufficient for use as an neuroprosthetic command interface.
PMID- 10188606
TI - Implantable electrode lead in a growing limb.
AB - An implantable electrode leadwire system used to provide limb function for
individuals with spinal cord injuries (SCI's) was evaluated in a series of
growing dogs to determine whether it could maintain its performance in the
presence of growth. Thirty implantable electrodes (15 epimysial and 15
intramuscular) were implanted in the forelimb muscles of six young dogs. The
electrodes' leads were tunneled subcutaneously and anchored proximally in the
shoulder with excess lead incorporated into the subcutaneous space to accommodate
growth. Six of the leads had some of this excess placed in pouches made from
surgical membrane while the other 24 leads had excess placed freely within the
subcutaneous space. Motor responses to the electrodes were tested before and
after growth with tendon force transducers and were compared to the performance
of new electrodes implanted to the same muscles of the mature dog during the
explant procedure. Measured were the pulse duration at which a measurable force
is first produced (threshold) and the percentage of the maximum force that could
be attained from the target muscle before activation of adjacent muscles (usable
force range). An analysis of variance indicated that there was no difference in
the usable force range (p = 0.62) of the original electrodes before and after
growth and that of the new electrodes placed at maturity. There was a difference
in the threshold (p = 0.001) which can be attributed to an increase in the values
measured from the original electrodes after growth. However, the increase in
threshold with growth averaged 6 micros which is not clinically significant and
can be accommodated through stimulation programming. Growth of the limb and
unwinding of excess lead were quantified by radiograph. Extension of the freely
placed excess lead was comparable to growth so that the pouch enclosures were
found to be unnecessary for facilitating lead expansion. By radiograph and
surgical observations, only two of 30 electrodes (both intramuscular) appeared to
have been subjected to lead tension, although they continued to provide adequate
motor responses. Insufficient excess lead was judged to be the cause of
dislodgment for one of these electrodes. Results of this study suggest that for
this implantable leadwire system, excess lead placed in the subcutaneous space
can unwind on demand with limb growth such that an electrode will remain in
position and provide a stable motor response.
PMID- 10188607
TI - Isometric torque about the knee joint generated by microstimulation of the cat L6
spinal cord.
AB - Isometric torque was generated about the knee joint by microstimulation of the
cat L6 spinal cord using a single microelectrode. The torque responses varied
with microstimulation location. Appreciable extension torque was generated by
microstimulation in ventrolateral locations of the L6 spinal cord. Stimulation
parameters (intensity, frequency and pulse-width) also influenced the extension
torque. Specific stimulation parameters (100 microA intensity, 40 Hz frequency
and 0.20 ms pulse-width) appear best suited for mapping the spinal cord based on
knee joint torque responses. Low levels of cocontraction of the extensor and
flexor could be achieved when extension torque was produced, but also varied with
the stimulation locations. There are locations in the L6 ventral horn where
microstimulation could evoke sustained extension for at least 4 min with only a
slight change in torque. This study suggests the possibility of restoring lower
limb function in patients with spinal cord injury above the lumbar level.
PMID- 10188608
TI - Chronic intracortical microstimulation (ICMS) of cat sensory cortex using the
Utah Intracortical Electrode Array.
AB - In an effort to assess the safety and efficacy of focal intracortical
microstimulation (ICMS) of cerebral cortex with an array of penetrating
electrodes as might be applied to a neuroprosthetic device to aid the deaf or
blind, we have chronically implanted three trained cats in primary auditory
cortex with the 100-electrode Utah Intracortical Electrode Array (UIEA). Eleven
of the 100 electrodes were hard-wired to a percutaneous connector for chronic
access. Prior to implant, cats were trained to "lever-press" in response to pure
tone auditory stimulation. After implant, this behavior was transferred to "lever
presses" in response to current injections via single electrodes of the implanted
arrays. Psychometric function curves relating injected charge level to the
probability of response were obtained for stimulation of 22 separate electrodes
in the three implanted cats. The average threshold charge/phase required for
electrical stimulus detection in each cat was, 8.5, 8.6, and 11.6 nC/phase
respectively, with a maximum charge/phase of 26 nC/phase and a minimum of 1.5
nC/phase thresholds were tracked for varying time intervals, and seven electrodes
from two cats were tracked for up to 100 days. Electrodes were stimulated for no
more than a few minutes each day. Neural recordings taken from the same
electrodes before and after multiple electrical stimulation sessions were very
similar in signal/noise ratio and in the number of recordable units, suggesting
that the range of electrical stimulation levels used did not damage neurons in
the vicinity of the electrodes. Although a few early implants failed, we conclude
that ICMS of cerebral cortex to evoke a behavioral response can be achieved with
the penetrating UIEA. Further experiments in support of a sensory cortical
prosthesis based on ICMS are warranted.
PMID- 10188609
TI - Optimal control of walking with functional electrical stimulation: a computer
simulation study.
AB - Bipedal locomotion was simulated to generate a pattern of activating muscles for
walking using electrical stimulation in persons with spinal cord injury (SCI) or
stroke. The simulation presented in this study starts from a model of the body
determined with user-specific parameters, individualized with respect to the
lengths, masses, inertia, muscle and joint properties. The trajectory used for
simulation was recorded from an able-bodied subject while walking with ankle-foot
orthoses. A discrete mathematical model and dynamic programming were used to
determine the optimal control. A cost function was selected as the sum of the
squares of the tracking errors from the desired trajectories, and the weighted
sum of the squares of agonist and antagonist activations of the muscle groups
acting around the hip and knee joints. The aim of the simulation was to study
plausible trajectories keeping in mind the limitations imposed by the spinal cord
injury or stroke (e.g., spasticity, decreased range of movements in some joints,
limited strength of paralyzed, externally activated muscles). If the muscles were
capable of generating the movements required and the trajectory was achieved,
then the simulation provided two kinds of information: 1) timing of the onset and
offset of muscle activations with respect to the various gait events and 2)
patterns of activation with respect to the maximum activation. These results are
important for synthesizing a rule-based controller.
PMID- 10188610
TI - The control of foot placement during compensatory stepping reactions: does speed
of response take precedence over stability?
AB - Rapid, reflex-like stepping movements are a prevalent and functional compensatory
reaction to destabilization, however, little is known about the underlying
control. In this paper, a model is developed to examine how speed and stability
demands affect control of foot placement during forward and backward compensatory
stepping reactions. The concept of the velocity stability margin (VSM) is
introduced to characterize the degree to which the horizontal velocity of the
falling body approaches biomechanical limits on the capacity to decelerate the
center of mass; analogous limits on center-of-mass displacement are quantified in
terms of the displacement stability margin (DSM). The model is used to predict,
for any initial step characteristics, the variation in DSM and VSM that would
occur as a function of changes in timing of foot placement. The VSM was found to
prevail over the DSM in establishing limits of stability. Model simulations
demonstrated that there typically exists a minimum swing duration that maximizes
speed of response while meeting minimum requirements for stability (VSM > or =
0), as well as a slower speed of response (longer swing duration) at which
stability (VSM) is maximized. Experimental data from platform-perturbation tests
in 20 healthy young (22-28) and older (65-81) adults were used, in conjunction
with the model, to investigate whether speed or stability takes precedence during
natural behavior. Control of single-step reactions appeared to favor stability;
although the model predicted that a minimally stable step (VSM = 0) could be
attained by swing durations as short as 30 ms, the observed swing durations were,
on average, 135 ms longer than this, and the average VSM was nearly as large
(80%) as the optimally stable value predicted by the model. Control of the
initial step of multiple-step reactions was distinctly different. The average
swing duration was only 55 ms greater than the minimally stable value and the
average VSM was 81% smaller than in the single-step reactions. This reduction in
VSM is consistent with a need to execute additional steps and appears to support
the validity of the model. This model may help to provide insight into the
biomechanical factors that govern the neural control of compensatory stepping
reactions.
PMID- 10188611
TI - Assessment of geometric and mechanical parameters in wheelchair seating: a
variability study.
AB - A measurement method has been developed to quantify the posture of able-bodied
subjects seated in their wheelchair. Fourteen geometric parameters were measured
in order to represent the pelvis, trunk and lower limbs orientations. They were
defined by digitizing the three-dimensional (3-D) position of 23 anatomical
landmarks using a mechanical articulated arm (Microscribe3D, Immersion
Corporation). Mechanical parameters were used to measure the maximum pressure,
mean pressure and peak pressure gradient on the seat and the back of the
wheelchair using a force sensing array (Vista Medical, Inc.). A third set of
parameters combining mechanical and geometric measurements were defined to
represent pelvic tilt and ischial pressure orientations. However, different types
of errors are associated to the measurement of these geometric and mechanical
parameters. The purpose of this study was to evaluate these errors and their
impact on the precision of the various parameters on a sample group of five able
bodied subjects. Results showed that variability of most of the geometric
parameters is below 2 degrees with the sagittal rotation of the pelvis presenting
the highest variability (3.8 degrees) and the thigh angle the lowest one (0.5
degrees). The variability of the mechanical parameters were respectively equal to
4.9% for the mean pressure, 9.3% for the peak pressure gradient and 16.9% for the
maximum pressure under ischial tuberosities. It is suggested that the method
proposed in this paper could be used as an accurate procedure to characterize the
posture of subjects sitting in a wheelchair.
PMID- 10188612
TI - A method for custom-contoured cushion design using interface pressure
measurements.
AB - The interface pressure distributions between flat foam cushions and the buttocks
of seated test subjects were compared to custom-contoured cushion surface shapes
generated with a seated-buttock contour gauge. Our hypothesis was that pressure
measurements could be used to generate a contour equivalent to that obtained with
a force-deflection contour gauge. The study was performed in a university medical
center using spinal cord injured (SCI) (12) and elderly (30) test subjects.
Interface pressure was measured using a pressure mapping pad. Contour shape was
measured using an electronic force-deflection contour gauge. Pressure and contour
information were reduced prior to analysis using singular value decomposition.
Polynomial regressions were performed on the values in the first singular vectors
of the corresponding pressure and contour decompositions. Relationships best
described by cubic polynomials were detected between pressure and contour shape
suggesting that interface pressure predicts optimal contour shape.
PMID- 10188613
TI - The effect of wrist angle on electrically evoked hand opening in patients with
spastic hemiplegia.
AB - This paper studied the effect of wrist angle on the amount of hand opening
achieved by electrical stimulation in people with spastic hemiplegia. With their
forearm in pronation, subjects were asked to relax while their affected wrist was
passively moved in steps of about 15 degrees from full flexion into extension.
Trains of stimuli were applied to the long finger extensor muscles through
surface electrodes on the forearm. At each wrist position stimulation was turned
on for a few seconds until hand opening equilibrated. Wrist angle and fingertip
positions were recorded using a three-dimensional (3-D) motion analysis system.
Maximal displacements between thumbtip and each fingertip occurred when the wrist
was fully flexed. As the wrist was extended, hand aperture achieved by electrical
stimulation progressively declined, reaching zero at 40 degrees of wrist
extension. We conclude that electrical stimulation can significantly increase the
grasp aperture of the hemiplegic hand, but this is strongly dependent on wrist
posture and accompanying voluntary effort.
PMID- 10188614
TI - Knee elasticity influenced by joint angle and perturbation intensity.
AB - The responses of the human knee joint system to small rotational displacements
were studied in the horizontal plane to eliminate the effect of gravity. Band
limited noise was used to produce up to +/-3 degrees angular perturbations to the
knee joint. Under these restricted conditions, the knee joint system could be
described by a linear, second-order model with the assumption that the mechanical
properties of the knee were constant over these small displacements. The
elasticity about the knee was influenced not only by the static joint angle but
also by the perturbation intensity. Realistic models of the knee joint system
should be modeled by a position-dependent, nonlinear system to remain valid over
a large range of rotation.
PMID- 10188615
TI - Evidence suggesting that the angiotensin II-sensitive intracellular Ca2+ pool is
reloaded from the external space in adrenal glomerulosa cells.
AB - Adrenal glomerulosa cells prelabeled with 45Ca2+ and perifused for 10 min with 10
nM angiotensin II (AII) in a dynamic perifusion system show a biphasic response
with an initial transient increase in 45Ca2+ efflux, followed by a sustained
phase of increased 45Ca2+ efflux. When labeled adrenal golmerulosa cells were
treated with 10 nM AII for three consecutive periods of 5 min, the transient
increase in 45Ca2+ efflux was observed only in the first period. However, when
40Ca2+ was measured in the perifusate using a Ca2+-sensitive electrode coupled to
the perifusion system, a transient increase in 40Ca2+ efflux was observed in each
period of AII treatment. Exposing the cells to AII for 1 min, the amount of
40Ca2+ effluxed out of the cells was 58.3 +/- 8.4 nmol/10(8) cells. In contrast,
when the cells were exposed to an increase in the external potassium (K+)
concentration of 4 to 12 mM during 1 min of perifusion, the amount of 40Ca2+
effluxed was 16 +/- 5 nmol/10(8) cells. These results indicate that AII induces
an increase in the Ca2+ concentration in a local domain outside of the plasma
membrane. This Ca2+ comes from AII-induced intracellular Ca2+ depletion and may
play a role in refilling intracellular Ca2+ stores.
PMID- 10188616
TI - Effects of a vasorelaxing factor liberated by the rat isolated atria on rat
aortic rings with and without endothelium.
AB - In 1993, Illanes et al. described a vasoactive factor, the auricular vasorelaxing
factor (AVF), by controlled distension of rat isolated atria. This factor
produces vasodilation, antagonizing the vasoconstrictor action of phenylephrine.
We now report assays by using isolated rat aortic rings and norepinephrine as a
vasoconstrictor. Isolated thoraxic aortic rings were mechanically deprived of
endothelium and subjected to the effects of increasing, cumulative concentrations
of 6.6 x 10(-11) M to 6.6 x 10(-7) M norepinephrine. AVF significantly decreases
the constrictor effect of norepinephrine assayed afterward, shifting the
vasoconstrictor dose-response relation to the right. The effect was the same in
rat aortic rings with or without endothelium. Subjecting aortic rings to control
vehicle samples did not alter the dose-response curve to norepinephrine. We
conclude that AVF antagonizes the norepinephrine vasoconstrictor effect in rat
isolated aortic rings and that the mechanism of this vasorelaxing effect is
independent of any contribution from the endothelial cells.
PMID- 10188617
TI - Anticancer drugs inhibit induction of NO synthase in rat in vivo.
AB - Nitric oxide (NO), synthesized by inducible NO synthase (iNOS) in immunoreactive
cells, plays important roles in their activities such as bactericidal and
tumoricidal functions. We examined the distribution of iNOS and evaluated the
effects of anticancer drugs, 4'-epi-doxorubicin (EPI-DXR) and mitomycin C (MMC),
on iNOS induction by lipopolysaccharide in rats. Ascites cells and bone marrow
showed the highest induction of iNOS in the tested organs. Administration of EPI
DXR to rats strongly inhibited iNOS induction in lung, ascites, and bone marrow,
but only slightly in liver and spleen. MMC administration inhibited the induction
in the most immune reactive organs.
PMID- 10188619
TI - Effects of vitamin C supplementation on plasma antioxidant status in unfed
periods.
AB - In this study, the antioxidant protection of ascorbic acid (AA) supplementation
during different unfed periods (24, 48, 120 h) was determined with blood lipid
peroxidation level (thiobarbituric acid reactive substances, TBARS) and compared
with plasma antioxidant sulfydryl group (RSH) content. Weight loss was induced by
increasing the unfed period together with vitamin C supplementation. Blood AA
levels decreased by starvation but increased by vitamin C supplementation. RSH
content in plasma also decreased with the unfed period; these decreases became
apparent by vitamin C supplementation. TBARS formation increased significantly by
AA supplementation in the 120-h starvation period.
PMID- 10188618
TI - Superior cervical ganglionectomy-induced lowering of intraocular pressure in
rabbits: role of prostaglandins and neuropeptide Y.
AB - At 22-24 h after unilateral ganglionectomy (SX), intraocular pressure (IOP) was
significantly (p < 0.001) reduced in SX eyes compared either with the
contralateral, normally innervated eyes or with baseline measurements. SX raised
prostaglandin E2 (PGE2), PGF2alpha, and neuropeptide Y (NPY) concentrations in
the aqueous humor but reduced these levels in the iris-ciliary body. At 22-24 h
after bilateral SX, flurbiprofen (0.03%) significantly (p < 0.001) inhibited the
reduction of IOP and the elevation of PGE2 and PGF2alpha levels in the aqueous
humor. We conclude that PGs mediate the reduction of IOP at 22-24 h after SX.
PMID- 10188620
TI - The effect of topical diltiazem on ocular hypertension induced by water loading
in rabbits.
AB - The aim of this work was to assess the effect of topical diltiazem on the ocular
hypertension induced by water loading in rabbits. The effect of three different
concentrations of diltiazem on the intraocular pressure rise produced by oral
administration of tap water (60 ml/kg) was tested in groups of nine or ten
rabbits each. When applied at the lowest concentration studied, topical diltiazem
was found to enhance the intraocular pressure rise after water loading. In
contrast, when applied at the highest concentration, diltiazem counteracted the
ocular hypertension caused by water loading. Although diltiazem, and probably
other calcium channel blockers, may be useful in the management of ocular
hypertension, the data obtained suggest that these drugs may have complex actions
on aqueous humor dynamics; therefore further studies in animal models for
glaucoma should be carried out before their clinical evaluation in humans.
PMID- 10188621
TI - Ethanol abolishes clonidine-induced impairment of baroreflex control of heart
rate in conscious rats.
AB - Our previous studies showed that the ability of ethanol or clonidine to alter the
baroreflex control of heart rate (baroreflex sensitivity, BRS) depends on the
functional activity of aortic baroreflexes. In this study, we investigated the
interaction between the two drugs on BRS in conscious rats with intact
baroreflexes (shamoperated, SO) and after aortic baroreceptor denervation (ABD).
The slope of the curve relating increments in mean arterial pressure induced by
phenylephrine to corresponding reflex bradycardic responses was taken as an index
of BRS. Ethanol (1 g/kg i.v.) significantly (p < 0.05) attenuated BRS in SO rats
(-1.7 +/- 0.13 versus -1.04 +/- 0.15 beats/min/mm Hg) but not in ABD rats.
Clonidine (30 microg/kg, i.v.) elicited significantly (p < 0.05) greater
hypotensive responses in conscious ABD compared with SO rats. The BRS was not
affected by clonidine administration in SO rats but showed significant (p < 0.05)
reductions in ABD rats. Ethanol (1 g/kg, i.v.) had no effect on the hypotensive
response to subsequently administered clonidine in ABD and SO rats; however, the
effect of the two drugs on BRS was variable. In ABD rats, the BRS values before
and after administration of ethanol and clonidine were similar, suggesting that
pretreatment with ethanol counteracted clonidine-evoked attenuation of BRS in
this rat preparation. In SO rats, the ethanol-clonidine combination produced a
significant (p < 0.05) decrease in BRS, similar to the effect of ethanol when
administered alone. These data confirm earlier findings that the aortic
baroreflex arc modulates the interaction of ethanol and clonidine with baroreflex
function. Further, the ability of ethanol to abolish clonidine-induced
attenuation of BRS in ABD rats may relate to the compound effects of the two
drugs on neuronal pathways participating in the central processing of
baroreflexes in these rats.
PMID- 10188622
TI - Intermediate dose of methotrexate toxicity in non-Hodgkin lymphoma.
AB - Methotrexate (MTX) is the chemotherapeutic for which the serum levels can be
detected. If the MTX level is detected in time, high toxicity risk can be
decreased. In this study, intermediate doses of MTX (1 g/m2) infusions are
administered to B-cell non-Hodgkin lymphoma patients between 3 and 13 years old.
The toxicity of MTX in accordance with serum levels and the toxicity of other
combined drugs are investigated. Blood samples were collected consecutively, and
MTX levels were detected by high-performance liquid chromatography. When
hematological, gastrointestinal, and renal toxicity scores were compared with the
24-h serum levels of MTX, they showed a significant positive correlation.
Hematological toxicity scores increased by Ifosfamide, Etoposide, and Cytarabine
combined with MTX without altering the serum levels. Antibiotic combination with
MTX has no effect on the toxicity scores. In conclusion, if MTX is combined with
other myelosuppressive, hepatotoxic, and nephrotoxic drugs, the measurement of
MTX serum levels alone is not a sufficient parameter to show the toxicity.
PMID- 10188623
TI - Effect of pineal indoles on the chick embryo.
AB - In a study on the embryotoxicity of pineal indoles on developing chick embryos in
vivo, the pineal indoles--namely, melatonin (MEL), methoxytryptamine (MTA) and
methoxytryptophol (MTP)--were injected into the yolk sacs of the chick embryos
through the air chambers of the eggs on the 4th day of incubation. The eggs were
opened and the embryos examined after 6, 10 or 14/15 days of incubation.
Abnormalities were found to occur mainly in the 6- and 10-day-old embryos, which
exhibited external malformations such as twisted vertebral column, abdominal
hernia, exteriorization of heart and viscera, defects of eye, beak and limb. From
the results obtained from embryos on the 14th or 15th day of incubation, MEL was
found to be the most toxic indole in regard to the mortality induced, whereas MTA
had the highest teratogenicity because of the frequent incidence of abnormal
embryos. Effect of MTP treatment on the development of chick embryos varied
greatly between doses, and there were no abnormal embryos found on the 14th or
15th day of incubation.
PMID- 10188624
TI - Screening of antioxidant action of various molds and protection of Monascus anka
against experimentally induced liver injuries of rats.
AB - Antioxidant action of various molds, which are traditionally used for the
production of foods or alcoholic beverages in Japan, was studied in vitro and in
vivo. Antioxidant action was evaluated by scavenging stable free radical 1,1
diphenyl-2-picrylhydrazyl (DPPH) and lipid peroxidation of rat liver microsomes.
Among 40 molds, 16 species showed the DPPH scavenging action, and the molds that
can scavenge the DPPH radical inhibited lipid peroxidation. The mold with the
strongest action, Monascus anka, was chosen for the investigation of a protective
action against liver injury of rats. When galactosamine (GalN, 400 mg/kg) or GalN
plus lipopolysaccharide (LPS, 0.5 microg/kg) was given intraperitoneally to rats
(Sprague-Dawley), aspartate aminotransferase (AST) and glutathione (GSH) S
transferase (GST) activities in serum were significantly increased. However, such
hepatotoxicities seen in the increase in serum enzyme levels were depressed when
the extract prepared from M. anka was given 1 and 15 h before the toxic
insultant. Liver microsomal GST activity, which is known to be activated by
oxidative stress, was increased by GalN or GaIN plus LPS treatment and the
increase was also inhibited by pretreatment with the extract. Pathomorphological
changes in the liver caused by GalN treatment also were prevented by the mold
extract. These results indicate that the extract of M. anka has radical
scavenging action and ameliorates chemically induced hepatotoxicity.
PMID- 10188625
TI - Modulation of insulin secretion by leptin.
AB - The present study examines the acute effect of leptin (50 nM) on insulin
secretion and on the fractional outflow rates of 45Ca2+ and 86Rb+ from pancreatic
islets isolated from male lean albino rats. Under a constant physiological
glucose concentration (5.6 mM), the addition of leptin to the perifusion medium
led to an increment in 45Ca2+ fractional outflow rate followed by a significant
(p < 0.05) increase (26%) in the insulin release. At low glucose concentration
(2.8 mM), leptin also elicited a significant (p < 0.05; 50-60%) increase in
insulin secretion. However, under supraphysiological (16.7 mM) glucose
concentration, the rapid first-phase insulin secretion response was abolished. At
low glucose levels, islets perifused in the presence of leptin presented a lower
86Rb+ fractional outflow rate compared with perifused controls. In contrast, when
glucose was switched to 16.7 mM, compared with controls, a slight increase in the
86Rb+ fractional outflow rate was observed instead. These in vitro data provide
evidence that, by changing K+ fluxes, leptin might modulate insulin secretion
from pancreatic islets.
PMID- 10188626
TI - Two B1 and B2 bradykinin receptor antagonists fail to inhibit the Ca2+ response
elicited by bradykinin in human skin fibroblasts.
AB - The elevation of intracellular [Ca2+] induced by bradykinin (Bk) was monitored
with fura-2 fluorescence in human skin fibroblasts. Neither [des
Arg10][Leu9]kallidin nor D-Arg[Hyp3,Thi5,D-Tic7,Oic8]bradykinin (HOE140)
inhibited the Ca2+ response stimulated by Bk. Moreover, each behaved as a partial
agonist causing the elevation of intracellular [Ca2+].
PMID- 10188627
TI - Effects of low ozone-oxygen concentrations on the acetylcholine release at the
mouse neuromuscular junction.
AB - The use of a mixture of low concentrations of ozone (O3) with oxygen (O2) have
been proved to be useful in different human pathological conditions. Owing to a
lack of both pharmacological and epidemiological basic studies, the scientific
consideration of this therapeutic potential is still inappropriate. Here, we
started, from an electrophysiological point of view, a study on the possible
effects of low O3 doses on the acetylcholine (ACh) release at the neuromuscular
junction. Indeed, some experimental conditions indicate a positive effect either
in maintaining cytosolic calcium (Ca2+) homeostasis or in increasing the efficacy
of the intracellular antioxidant systems. Furthermore, a positive action on the
kinetics of some antioxidant enzymes must be taken into account as a possible
molecular mechanism in the regulation of the function of cellular homeostasis.
Our data demonstrate a reduction of evoked ACh release in the mouse neuromuscular
junction. O3 affects neither the spontaneous ACh release nor the kinetics of the
ACh-receptor-channel complex. The results are compatible with a reduction of
intracellular Ca2+ and proved a molecular action of O3.
PMID- 10188628
TI - Suppression of gastric mucosal inflammatory responses to Helicobacter pylori
lipopolysaccharide by sulglycotide.
AB - The effect of the antiulcer agent sulglycotide on gastric epithelial cell
apoptosis and the expression of tumor necrosis factor-alpha (TNF-alpha) and
interleukin-4 (IL-4) during Helicobacter pylori lipopolysaccharide-induced acute
gastritis was investigated. Rats, pretreated twice daily for 3 consecutive days
with sulglycotide at 200 mg/kg or vehicle, were subjected to surface epithelial
application of H. pylori lipopolysaccharide (50 microg/animal), and, after 4
additional days on the drug or vehicle regimen, their mucosal tissue was used for
histologic assessment, quantitation of TNF-alpha and IL-4, and the assay of
epithelial cell apoptosis. In the absence of sulglycotide, H. pylori
lipopolysaccharide caused acute mucosal responses manifested by the inflammatory
infiltration of the lamina propria with lymphocytes and plasma cells, edema,
hyperemia, and epithelial hemorrhage. These responses were accompanied by an 11
fold increase in epithelial cell apoptosis and a 9-fold enhancement of the
mucosal expression of proinflammatory cytokine TNF-alpha. However, the mucosal
expression of regulatory cytokine IL-4 decreased by 15%. Treatment with
sulglycotide produced significant (56.6%) reduction in the extent of acute
mucosal inflammatory changes caused by H. pylori lipopolysaccharide. Moreover,
the effect of sulglycotide was manifested in an 88.3% reduction in the epithelial
cell apoptosis and a 69.1% decrease in the mucosal expression of TNF-alpha,
whereas the expression of IL-4 showed only marginal (6%) enhancement. The results
suggest that the cytoprotective agent sulglycotide suppresses the inflammatory
and apoptotic events elicited in gastric mucosa by H. pylori lipopolysaccharide
through stimulation of TNF-alpha expression.
PMID- 10188629
TI - Amiodarone is a pharmacologically safe drug for porphyrias.
AB - Amiodarone (AD) is an effective antidysrythmic drug, however, there can be
serious side effects, such as hepatic and neurological alterations, as well as
skin photosensitization, as seen in porphyrias. Clinical signs in porphyrias
might be triggered by the so-called porphyrinogenic drugs. Without sound basis,
Amiodarone has been classified as an unsafe drug for porphyric patients. The aim
of this work has been to study the effect of AD, both in vivo and in vitro, on
heme metabolism. In the in vivo assays, the activities of 5-aminolevulinate
synthetase (ALA-S), ALA dehydratase (ALA-D), porphobilinogenase (PBGase) and PBG
deaminase (PBG-D) in blood, liver, and kidney; hepatic and fecal porphyrins,
urinary ALA, PBG and porphyrins in male mice strain CF1 treated with AD (100 mg
i.p. daily) for 1 week and 1 month, were measured. No significanat differences
were found for any of these parameters in the AD treated animals as compared to
controls. In the in vitro experiments human blood, and mice blood, liver, and
kidney, were used to measure the activities of ALA-S, ALA-D, PBGase, PBG-D and
uroporphyrinogen decarboxylase, in the presence of varying concentrations of AD
(0.0172-4.304 mM). AD did not modify any of the enzyme activities. All of the
above biochemical parameters were studied in 17 cardiac patients under AD
treatment for 3 to 20 years. Neither the activities of the heme enzymes, nor the
levels of precursors and porphyrins in urine and plasma were altered. These
findings clearly demonstrate that AD is a pharmacologically safe drug and can be
used for the treatment of associated pathologies in porphyrias.
PMID- 10188630
TI - Kinetic analysis of GM1 effects on haloperidol-induced dopaminergic
supersensitivity.
AB - The relative affinity of metoclopramide as indicated by K(B) values was
calculated in control and in haloperidol-withdrawn rats treated or not with
monosialoganglioside-1 (GM1) by using dose-response curves constructed for
apomorphine-induced stereotyped behavior. Haloperidol withdrawal decreased K(B)
data--that is, increased the D2-receptor affinity for metoclopramide. GM1
treatment per se did not modify K(B) values but, when given in combination with
haloperidol, GM1 induced a decrease in K(B) values. No differences were found in
K(B) data when GM1 was administered after withdrawal from haloperidol.
PMID- 10188631
TI - Different actions in the rat prostatic and epididymal vas deferens of
cyclopiazonic acid or ryanodine on noradrenaline-induced contractions.
AB - The effects of ryanodine, cyclopiazonic acid (CPA), and nifedipine on
noradrenaline (NA)-induced contractions were investigated to characterize the
role of the sarcoplasmic reticulum (SR) in the epididymal and prostatic parts of
the rat vas deferens. In the epididymal part, NA (0.1, 1, and 100 microM) evoked
marked rhythmic contractions superimposed on a tonic response. NA (100 microM)
evoked biphasic tonic contractions consisting of a fast (initial) component and
delayed secondary components. Nifedipine (1 microM) suppressed the rhythmic
activity and the contractions to low NA concentrations and markedly reduced the
components of the response to NA (100 microM). Contractions of the epididymal
part to NA (0.1, 1, and 100 microM) were not blocked by ryanodine (1-30 microM)
or CPA (1-30 microM). The secondary component in the response to NA (100 microM)
was enhanced by CPA (> or =10 microM). Thus in the epididymal part, NA stimulates
contraction predominantly by mobilizing extracellular calcium. However, a
residual nifedipine-insensitive contraction to NA (100 microM) was observed and
was not blocked by ryanodine (30 microM) or CPA (30 microM). In the prostatic
part, NA evoked mainly tonic contractions. The response to NA (100 microM)
consisted of three distinct components. Nifedipine (1 microM) reduced the
contractions to low concentrations of NA (0.1 and 1 microM) and all three
components of the response to NA (100 microM). Contractions of the prostatic part
to low concentrations of NA (0.1 and 1 microM) were not blocked by CPA (30
microM) or ryanodine (30 microM). The components of the response to NA (100
microM) were affected differently by the drugs. Ryanodine (17-30 microM) or CPA
(1-30 microM) suppressed the initial component and reduced the second component.
The third component was largely unaffected by CPA but reduced by ryanodine. In
the additional presence of nifedipine (1 microM), the residual components of NA
(100 microM) response were markedly reduced and the contractions to low
concentrations of the agonist virtually abolished. These results suggest that NA
contracts the prostatic part by mobilizing both extra- and intracellular calcium.
These results show that NA-induced contractions of the epididymal and prostatic
parts of the rat vas deferens differ in sensitivity to ryanodine or CPA. The
results suggest that, during stimulation of the epididymal part, the SR functions
mainly to buffer calcium entering through nifedipine-sensitive voltage-gated
calcium channels. In contrast, in the prostatic part, the SR serves mainly as a
source of calcium and contributes more to contractions evoked by higher
concentrations of the agonist.
PMID- 10188632
TI - Widespread expression of olfactory cyclic nucleotide-gated channel genes in rat
brain: implications for neuronal signalling.
AB - The cyclic nucleotides cAMP and cGMP are important intracellular messengers
involved in a wide variety of signal transduction events in the nervous system.
It has been proposed that cAMP/cGMP elicit some of their effects through direct
gating of a novel class of Ca2+ -permeable ion channels that are termed cyclic
nucleotide-gated (CNG) channels. Previous studies have identified the expression
of a gene encoding one major CNG channel subtype, the olfactory receptor neuron
alpha subunit, in the brain [El-Husseini et al. (1995) NeuroReport 6:1331-1335;
Kingston et al. (1996a) Proc. Natl. Acad. Sci. U.S.A. 93:10440-10445; Bradley et
al. (1997) J. Neurosci. 17:1993-2085]. We, therefore, proposed that the actions
of cAMP/cGMP on neurons in the brain might occur through the activation of these
CNG channels. To determine how widespread such a function might be, the regional
and cellular distribution of the olfactory CNG channel alpha subunit has been
examined in detail. Primers for multiple portions of the olfactory CNG channel
were used in polymerase chain reaction (PCR) to amplify cDNA reverse-transcribed
from several brain regions. The identities of PCR products were confirmed with
Southern blots and by sequencing. In situ hybridization experiments demonstrated
localization of CNG channel mRNA in discrete neuronal populations throughout the
brain. In agreement with previous work, relatively strong hybridization signals
are present in neuronal cell bodies of the cerebellum, olfactory bulb, cerebral
cortex, and brainstem. Additionally, somewhat lesser signals are found in
thalamus, hypothalamus, midbrain, and spinal cord while no hybridization signal
was detectable in the caudate nucleus. This surprisingly wide distribution
throughout the rat brain strengthens the hypothesis that CNG channels may
influence numerous processes as downstream effectors of cyclic nucleotide
cascades. Interestingly, the distribution of CNG channels is very similar to that
of the nitric oxide/cGMP system, suggesting that one function of CNG channels in
the brain could be to link diffusible messengers to elevated Ca2+ entry into
neurons.
PMID- 10188633
TI - Stress induces Fos expression in neurons of the thalamic paraventricular nucleus
that innervate limbic forebrain sites.
AB - The paraventricular nucleus of the thalamus (PVT) is a midline thalamic nucleus
that responds strongly to exposure to various stressors. Many of the projection
targets of PVT neurons, including the medial prefrontal cortex, nucleus
accumbens, and central/basolateral nuclei of the amygdala, are also activated by
stress. We sought to determine if PVT neurons that respond to stress are those
that project to one or more of these forebrain sites. Retrograde tract tracing
combined with immunohistochemical detection of Fos protein-like immunoreactivity
was used to assess the activation of target-specific populations of PVT
projection neurons by mild footshock stress in the rat. Stress markedly increased
Fos protein-like immunoreactivity in PVT neurons, but without regard to the
projection target of the thalamic neurons. Thus, the percentage of PVT cells that
were retrogradely labeled from either the prefrontal cortex, nucleus accumbens,
or amygdala, and that expressed Fos-like immunoreactivity did not differ
substantially across the three forebrain sites. These data suggest that the PVT
may have a role as a generalized relay for information relating to stress, and
may serve an important role in the stress-induced activation of limbic forebrain
areas.
PMID- 10188634
TI - Opioid peptide receptor studies, 11: involvement of Tyr148, Trp318 and His319 of
the rat mu-opioid receptor in binding of mu-selective ligands.
AB - Previous data obtained with the cloned rat mu opioid receptor demonstrated that
the "super-potent" opiates, ohmefentanyl (RTI-4614-4) and its four enantiomers,
differ in binding affinity, potency, efficacy, and intrinsic efficacy. Molecular
modeling (Tang et al., 1996) of fentanyl derivatives binding to the mu receptor
suggests that Asp147, Tyr148, Trp318, and His319 are important residues for
binding. According to this model, Asp147 interacts with the positively charged
opiate agonist to form potent electrostatic and hydrogen-bonding interactions. In
this study, the role of weak electrostatic and hydrogen-bonding "pi-pi"
interactions of the O atom of the carbonyl group and the phenyl ring structures
of RTI-4614-4 and its four enantiomers with residues Tyr148, Trp318, and His319
were explored via site-directed mutagenesis. Tyr148 (in transmembrane helix 3
{TMH3}), Trp318 (TMH7), and His319 (TMH7) were individually replaced with
phenylalanine or alanine. Receptors transiently expressed in COS-7 cells were
labeled with [125I]IOXY according to published procedures. Mutation of Tyr148 to
phenylalanine reduced the binding affinities of some mu-selective agonists (2-7
fold) but did not alter the affinities of DAMGO, naloxone, and the non-selective
opiates etorphine and buprenorphine. In contrast, this mutation significantly
increased the binding affinities (decreased the Kd values) of [D-Ala2,D
Leu5]enkephalin, IOXY, and dermorphin. Mutation of Trp318 decreased opioid
receptor binding to almost undetectable levels. Substitution of alanine for
His319 significantly reduced binding affinities for the opioid ligands tested
(1.3- to 48-fold), but did not alter the affinities of naloxone and bremazocine.
These results indicate the importance of Tyrl48 and His319 for the binding of
fentanyl derivatives to the mu receptor. Functional studies using the mutant
receptors will provide additional insight into the mechanism of action of RTI
4614-4 and its four enantiomers.
PMID- 10188635
TI - Modulation of GABA release by dopamine in the substantia nigra.
AB - The role of specific dopamine receptor subtypes in the regulation of GABA release
in the substantia nigra was investigated using microdialysis in the awake rat.
Both basal and potassium-stimulated changes in the extracellular concentrations
of GABA were examined in response to the local perfusion of tetrodotoxin (TTX),
the D1 agonist SKF 38393, or the D2 agonist LY 171555 through the microdialysis
probe in the substantia nigra. Although TTX (1 microM) did not alter the basal
extracellular concentrations of GABA in the substantia nigra, it attenuated the
potassium-stimulated (80 mM K+) release of GABA. SKF 38393 had no effect on basal
extracellular concentrations of GABA, but did potentiate K+ -stimulated release
of GABA in a concentration-dependent manner. The potentiated response at the
highest concentration of SKF 38393 (100 microM) was blocked by the D1 antagonist
SCH 23390. In contrast to the effect of the D1 agonist, the D2 agonist LY 171555
attenuated the stimulated release of GABA. These data indicate that although
basal extracellular concentrations of GABA in the substantia nigra may not be
derived from neuronal pools, K+ -stimulated release of GABA is impulse-mediated
and is modulated by the D1 and the D2 receptors. Local interactions between
dopamine and GABA in the substantia nigra may have important implications for the
direct regulation of basal ganglia efferent activity and motor behavior.
PMID- 10188636
TI - Maternal deprivation of neonatal rats produces enduring changes in dopamine
function.
AB - Isolation-rearing of weanling rats produces a syndrome of behavioral and
neurochemical effects that are indicative of enhanced ventrostriatal dopamine
function observed in adulthood. By contrast, maternal deprivation of neonatal
rats decreases behavioral responses to dopamine agonists when tested in adults,
which may indicate the opposite situation. However, in the present study it is
reported that in vivo microdialysis of the nucleus accumbens (NAC) revealed
enhanced release of dopamine (DA) in response to both d-amphetamine and high K+
perfusate in maternally deprived subjects. Thus, behavioral responses to d
amphetamine are diminished in maternally deprived rats despite apparent increases
in presynaptic dopaminergic function in the NAC.
PMID- 10188637
TI - Doses of GBR12909 that suppress cocaine self-administration in non-human primates
substantially occupy dopamine transporters as measured by [11C] WIN35,428 PET
scans.
AB - GBR12909 (GBR) is a high-affinity, selective, and long-acting inhibitor of
dopamine (DA) uptake that produces a persistent and noncompetitive blockade of DA
transporters and substantially reduces cocaine-induced increases in extracellular
DA in the nucleus accumbens of rats. Prior studies showed that intravenous
infusion of GBR to Rhesus monkeys selectively reduced (1 mg/kg) and eliminated (3
mg/kg) cocaine self-administration. This study tested the hypothesis that doses
of GBR that reduce cocaine self-administration in nonhuman primates produce
significant occupation of DA transporters. DA transporters were quantitated in
two baboons using [11C]WIN35,428 and positron emission tomography (PET). Each
baboon underwent paired control/blocked PET scans (performed on three separate
study days, 3-4 weeks apart). On the first scan the baboon received saline (3
ml/kg) 90 minutes before the injection of the radiotracer. GBR (1 mg/kg i.v.) was
infused 90 minutes before the second [11C]WIN 35,428 study. The same experimental
design was repeated with GBR doses of 3 and 10 mg/kg, respectively. Doses of 1 (n
= 2), 3 mg/kg (n = 2), and 10 mg/kg (n = 2) reduced binding potential by 26, 53,
and 72%, respectively. GBR was well tolerated in all baboons. These results
demonstrate that doses of GBR that suppress cocaine self-administration in
nonhuman primates also produce high occupancy of the DA transporter. These data
strongly suggest that occupancy for the DA transporter by GBR explains its
ability to attenuate cocaine-induced increases in extracellular DA and to
suppress cocaine self-administration. Moreover, these data suggest that
experimental human studies of orally administered GBR to test the DA hypothesis
of cocaine addiction should use doses that produce at least 70% occupancy of the
DA transporter.
PMID- 10188638
TI - Dopamine D3 receptor antisense administration reduces basal c-fos and NGFI-B mRNA
levels in the rat forebrain.
AB - The physiological role of the dopamine D3 receptor is still unclear. The absence
of selective pharmacological tools that can discriminate D3 over D2 receptor
subtype activity is a major drawback in the elucidation of D3-mediated functions.
In order to study D3 receptor actions in rat brain, we have developed an
antisense strategy, using oligodeoxynucleotide (ODN) directed against the mRNA of
the D3 receptor. Dopamine D2-like agents induce a cascade of events that affect
numerous genes in the CNS. Transcription factors are among the most dramatically
affected. Using the antisense strategy, we explored the involvement of the D3
receptor on the expression of two classes of transcription factors, the c-fos and
NGFI-B. Intracerebroventricular injections of ODNs were made into the lateral
ventricle (8 microg/hour, for 5 days). The effect of antisense administration on
dopamine D1, D2, and D3 receptor binding was measured by means of receptor
autoradiography, whereas transcription factor mRNA levels (c-fos and NGFI-B) were
evaluated by in situ hybridization using specific complementary RNA probes.
Dopamine D3 receptor levels were significantly decreased in the shell of nucleus
accumbens of rats that received the D3 antisense ODN, whereas dopamine D1 and D2
receptor levels were not affected. Basal c-fos mRNA levels were concomitantly
reduced in both cingulate and medial prefrontal cortices. Basal NGFI-B mRNA
levels were also reduced in the cingulate cortex, shell of nucleus accumbens, and
in the dorsomedial striatum, whereas the core of nucleus accumbens and the
dorsolateral striatum were not affected after D3 antisense ODN treatments. Our
results suggest that D3 receptors may tonically regulate transcription factor
expression in rat forebrain. This supports the hypothesis of a constitutive
activity of the D3 receptor in vivo.
PMID- 10188639
TI - Corticosterone regulation of serotonin transporter and 5-HT1A receptor expression
in the aging brain.
AB - Hypercortisolemia is often observed in patients suffering from major depression.
As the serotonergic (5-hydroxytryptamine; 5-HT) system plays a major role in the
etiology of depression, a loss of endocrine and neurotransmitter system
interactions, including corticosterone regulation of 5-HT transporter (5-HTT) and
5-HT receptor expression, may underlie age-related deficits in the regulation of
the hypothalamic-pituitary-adrenal (HPA) axis and correlate with an increased
incidence of depression with advancing age. In this study, female Fischer 344
rats, ages 3, 13, and 18 months, were bilaterally adrenalectomized and
supplemented for 3 weeks with corticosterone (0, 200, or 600 mg; LC, MC, or HC,
respectively) containing 21 day sustained-release pellets implanted
subcutaneously. Quantitative autoradiography of hippocampal and cortical regions
using [3H]citalopram revealed a significant decrease in hippocampal 5-HTT binding
in the 3-month HC treatment group compared to age-matched MC and LC groups; this
loss was not present in the 13- or 18-month groups. Similarly, quantitative
autoradiography using the radiolabeled 5-HT(1A) receptor agonist 8-hydroxy-2-(di
N-propylamino) tetralin demonstrated a significant decline in receptor density in
3- and 13-month MC and HC groups as compared to age-matched LC groups in the
hippocampus. These hormone treatments (MC or HC), however, failed to alter
hippocampal 5-HT(1A) binding site density in the 18-month groups as compared to
the age-matched LC group. The 5-HT(2A) receptor was also evaluated using
[3H]ketanserin and showed no age- or corticosterone-related changes in the
cortex. Overall, an age-associated deficit in the regulation of the hippocampal
serotonergic system by varied corticosterone treatment was revealed in the
present study, which may underlie the increased incidence of depression and
hypercortisolemia found with advancing age.
PMID- 10188640
TI - Decreased hippocampal (CA3) NMDA receptors in schizophrenia.
PMID- 10188641
TI - A piece of my mind. A mother's voice.
PMID- 10188642
TI - Technical and clinical progress in telemedicine.
PMID- 10188643
TI - AIDS researchers target poor adherence.
PMID- 10188644
TI - Weaving webs for physicians.
PMID- 10188645
TI - Scary scenarios spark action at bioterrorism symposium.
PMID- 10188646
TI - Applying the evidence in Australia.
PMID- 10188647
TI - From the Centers for Disease Control and Prevention. Hemolysis associated with
25% human albumin diluted with sterile water--United States, 1994-1998.
PMID- 10188648
TI - From the Centers for Disease Control and Prevention. Nosocomial group A
streptococcal infections associated with asymptomatic health-care workers-
Maryland and California, 1997.
PMID- 10188649
TI - Control of outbreaks due to organisms producing extended-spectrum beta
lactamases.
PMID- 10188651
TI - Marginal medicine.
PMID- 10188650
TI - Combating antimicrobial resistance in India.
PMID- 10188652
TI - Marginal medicine.
PMID- 10188653
TI - Marginal medicine.
PMID- 10188654
TI - Respiratory effects of secondhand smoke.
PMID- 10188655
TI - Doctoring doctors.
PMID- 10188656
TI - Effect of immediate-release glipizide on hypoglycemic vulnerability in fasted,
elderly patients with type 2 diabetes.
PMID- 10188657
TI - Genotypic analysis of HIV-1 isolates to identify antiretroviral resistance
mutations from source patients involved in health care worker occupational
exposures.
PMID- 10188658
TI - Managed care and physicians' provision of charity care.
AB - CONTEXT: Health system changes may be affecting the ability of physicians to
provide care with little or no compensation from patients who are uninsured and
under-insured and may result in decreased access to physicians for uninsured
persons. OBJECTIVE: To examine the association between managed care and
physicians' provision of charity care. DESIGN: The 1996-1997 Community Tracking
Study physician survey. SETTING AND PARTICIPANTS: A nationally representative
sample of 10881 physicians from 60 randomly selected communities. MAIN OUTCOME
MEASURE: The number of hours in the month prior to the interview that the
physician provided care for free or at reduced fees because of the financial need
of the patient. RESULTS: Overall, 77.3% of respondents provided an average of
10.3 hours of charity care per month [corrected]. Physicians who derive at least
85% of their practice revenue from managed care plans were considerably less
likely to provide charity care and spend fewer hours providing charity care than
physicians with little involvement in managed care plans (P = .01). In addition,
physicians who practice in areas with high managed care penetration provided
fewer hours of charity care than physicians in other areas, regardless of their
own level of involvement with managed care (P<.01). Differences in charity care
provision were also shown for other important factors, including ownership of the
practice and practice arrangements (more charity care occurred in solo and 2
physician practices; P<.01). CONCLUSION: Physicians involved with managed care
plans and those who practice in areas with high managed care penetration tend to
provide less charity care.
PMID- 10188659
TI - Market forces and unsponsored research in academic health centers.
AB - CONTEXT: Increased competitive pressures on academic health centers may result in
reduced discretionary funds from patient care revenues to support the performance
of unsponsored research, including institutionally funded and faculty-supported
activities. OBJECTIVE: To measure the amount and distribution of unsponsored
research activities and their outcomes. DESIGN AND SETTING: Survey conducted in
academic year 1996-1997 of 2336 research faculty in 117 medical schools.
Responses were weighted to provide national estimates. MAIN OUTCOME MEASURES:
Institutionally funded research as a proportion of total direct costs of research
was compared across stages of market competition. Logistic regression was used to
assess the relationship of performing unsponsored research to faculty
characteristics and market stage. RESULTS: Overall, 43% of faculty received
institutional funding for research. Young faculty were more likely than others to
receive institutional support (adjusted odds ratio [OR], 1.4; 95% confidence
interval [CI], 1.1-1.9; P = .004). The amount of institutional support as a
proportion of total funding was more than twice as high in less competitive
markets (6.1%) compared with the most competitive markets (2.5%; P = .05). Most
faculty (55%) performed faculty-supported research. Clinical researchers (OR,
1.6; 95% CI, 1.1-2.3), principal investigators (OR, 4.3; 95% CI, 2.8-7.0),
faculty with high levels of research effort (OR, 6.2; 95% CI, 4.0-9.5) or
institutional funding (OR, 1.9; 95% CI, 1.4-2.6), and faculty in the most
competitive markets (OR, 1.9; 95% CI, 1.4-2.5) were more likely than others to
conduct faculty-supported research. When undertaken by clinical researchers,
these activities were supported by clinical income, extra hours worked, and
discretionary funds, and often led to publications (76%) or grant awards (51%).
CONCLUSIONS: Many academic health center faculty receive institutional support to
conduct their research or fund the research themselves. Market pressures may be
affecting the level of institutional funding available to faculty.
PMID- 10188660
TI - Risk factors for parvovirus B19 infection in pregnancy.
AB - CONTEXT: Parvovirus B19 infection during pregnancy has been associated with fetal
death. However, the incidence of and risk factors for infection in pregnant women
have not been well studied. OBJECTIVES: To estimate a pregnant woman's risk of
infection with parvovirus B19 in epidemic and endemic situations and to study
risk factors for infection. DESIGN: Population-based cohort study conducted
between November 1992 and June 1994. SETTING: Three regions in Denmark.
PARTICIPANTS: A total of 30946 pregnant women from a consecutive and population
based screening. MAIN OUTCOME MEASURES: Specific IgG antibodies in serum samples
obtained in the first trimester of pregnancy and from the newborn infant to
assess past infection and seroconversion. Information on family structure,
educational background, socioeconomic status, and pregnancy outcome was obtained
from national registers. RESULTS: Based on 30 946 serum samples, 65.0% of
pregnant women had evidence of past infection. Annual seroconversion rates among
susceptible women during endemic and epidemic periods were 1.5% (95% confidence
interval [CI], 0.2%-1.9%) and 13.0% (95% CI, 8.7%-23.1 %), respectively. Baseline
seropositivity was significantly correlated with increasing number of siblings,
having a sibling of the same age, number of own children, and occupational
exposure to children. Risk of acute infection increased with the number of
children in the household as follows: 0 children odds ratio (OR), 1 (reference);
1 child OR, 3.17 (95% CI, 2.24-4.49); 2 children OR, 5.47 (95% CI, 3.55-8.45); 3
or more children OR, 7.54 (95% CI, 3.80-14.94). Having children aged 6 to 7 years
resulted in the highest rate of seroconversion among mothers (6.8%; OR, 4.07; 95%
CI, 1.89-8.73). Compared with other pregnant women, nursery school teachers had a
3-fold increased risk of acute infection (OR, 3.09; 95% CI, 1.62-5.89).
Population-attributable risk of seroconversion was 55.4% for number of own
children and 6.0% for occupational exposure. CONCLUSIONS: The risk of infection
is high for susceptible pregnant women during epidemics and associated with the
level of contact with children. Nursery school teachers have the highest
occupational risk, but most infections seem to be the result of exposure to the
woman's own children.
PMID- 10188661
TI - Pregnancy outcome following gestational exposure to organic solvents: a
prospective controlled study.
AB - CONTEXT: Numerous women of childbearing age are exposed occupationally to organic
solvents. Previous retrospective studies have reported conflicting results
regarding teratogenic risk. OBJECTIVE: To evaluate pregnancy and fetal outcome
following maternal occupational exposure to organic solvents. DESIGN: A
prospective, observational, controlled study. SETTING: An antenatal counseling
service in Toronto, Ontario. PATIENTS: One hundred twenty-five pregnant-women who
were exposed occupationally to organic solvents and seen during the first
trimester between 1987 and 1996. Each pregnant woman who was exposed to organic
solvents was matched to a pregnant woman who was exposed to a nonteratogenic
agent on age (+/-4 years), gravidity (+/-1), and smoking and drinking status.
MAIN OUTCOME MEASURE: Occurrence of major congenital malformations. RESULTS:
Significantly more major malformations occurred among fetuses of women exposed to
organic solvents than controls (13 vs 1; relative risk, 13.0; 95% confidence
interval, 1.8-99.5). Twelve malformations occurred among the 75 women who had
symptoms temporally associated with their exposure, while none occurred among 43
asymptomatic exposed women (P<.001). (One malformation occurred in a woman for
whom such information was missing.) More of these exposed women had previous
miscarriage while working with organic solvents than controls (54/117 [46.2%] vs
24/125 [19.2%]; P<.001). However, exposed women who had a previous miscarriage
had rates of major malformation that were similar to exposed women who had no
previous miscarriage. CONCLUSIONS: Occupational exposure to organic solvents
during pregnancy is associated with an increased risk of major fetal
malformations. This risk appears to be increased among women who report symptoms
associated with organic solvent exposure. Women's exposure to organic solvents
should be minimized during pregnancy. Symptomatic exposure appears to predict
higher fetal risk for malformations.
PMID- 10188662
TI - Accuracy of data in abstracts of published research articles.
AB - CONTEXT: The section of a research article most likely to be read is the
abstract, and therefore it is particularly important that the abstract reflect
the article faithfully. OBJECTIVE: To assess abstracts accompanying research
articles published in 6 medical journals with respect to whether data in the
abstract could be verified in the article itself. DESIGN: Analysis of simple
random samples of 44 articles and their accompanying abstracts published during 1
year(July 1, 1996-June 30, 1997) in each of 5 major general medical journals
(Annals of Internal Medicine, BMJ, JAMA, Lancet, and New England Journal of
Medicine) and a consecutive sample of 44 articles published during 15 months
(July 1, 1996-August 15, 1997) in the CMAJ. MAIN OUTCOME MEASURE: Abstracts were
considered deficient if they contained data that were either inconsistent with
corresponding data in the article's body (including tables and figures) or not
found in the body at all. RESULTS: The proportion of deficient abstracts varied
widely (18%-68%) and to a statistically significant degree (P<.001) among the 6
journals studied. CONCLUSIONS: Data in the abstract that are inconsistent with or
absent from the article's body are common, even in large-circulation general
medical journals.
PMID- 10188663
TI - Prevention of a first stroke: a review of guidelines and a multidisciplinary
consensus statement from the National Stroke Association.
AB - OBJECTIVE: To establish, in a single resource, up-to-date recommendations for
primary care physicians regarding prevention strategies for a first stroke.
PARTICIPANTS: Members of the National Stroke Association's (NSA's) Stroke
Prevention Advisory Board and Cedars-Sinai Health System Department of Health
Services Research convened on April 9, 1998, in an open meeting. The conference
attendees, selected to participate by the NSA, were recognized experts in
neurology (9), cardiology (2), family practice (1), nursing (1), physician
assistant practices (1), and health services research (2). EVIDENCE: A literature
review was carried out by the Department of Health Services Research, Cedars
Sinai Health System, Los Angeles, Calif, using the MEDLINE database search for
1990 through April 1998 and updated in November 1998. English-language
guidelines, statements, meta-analyses, and overviews on prevention of a first
stroke were reviewed. CONSENSUS PROCESS: At the meeting, members of the advisory
board identified 6 important stroke risk factors (hypertension, myocardial
infarction [MI], atrial fibrillation, diabetes mellitus, blood lipids,
asymptomatic carotid artery stenosis), and 4 lifestyle factors (cigarette
smoking, alcohol use, physical activity, diet). CONCLUSIONS: Several
interventions that modify well-documented and treatable cardiovascular and
cerebrovascular risk factors can reduce the risk of a first stroke. Good evidence
for direct stroke reduction exists for hypertension treatment; using warfarin for
patients after MI who have atrial fibrillation, decreased left ventricular
ejection fraction, or left ventricular thrombus; using 3-hydroxy-3 methylglutaryl
coenzyme A (HMG-CoA) reductase inhibitors for patients after MI; using warfarin
for patients with atrial fibrillation and specific risk factors; and performing
carotid endarterectomy for patients with stenosis of at least 60%. Observational
studies support the role of modifying lifestyle-related risk factors (eg,
smoking, alcohol use, physical activity, diet) in stroke prevention. Measures to
help patients improve adherence are an important component of a stroke prevention
plan.
PMID- 10188665
TI - A 24-year-old woman with anorexia nervosa, 1 year later.
PMID- 10188664
TI - An 87-year-old woman taking a benzodiazepine.
PMID- 10188666
TI - Who is responsible for the common good in a competitive market?
PMID- 10188667
TI - The need for concrete improvement in abstract quality.
PMID- 10188668
TI - Tobacco and alcohol use in G-rated children's animated films.
AB - CONTEXT: Tobacco and alcohol use among youth are major public health problems,
but the extent to which children are routinely exposed to tobacco and alcohol
products in children's films is unknown. OBJECTIVE: To identify the prevalence
and characteristics associated with tobacco and alcohol use portrayed in G-rated,
animated feature films. Design All G-rated, animated feature films released
between 1937 and 1997 by 5 major production companies (Walt Disney Co, MGM/United
Artists, Warner Brothers Studios, Universal Studios, and 20th Century Fox) that
were available on videotape were reviewed for episodes of tobacco and alcohol
use. MAIN OUTCOME MEASURES: Presence of tobacco and alcohol use in each film,
type of tobacco or alcohol used, duration of use, type of character using
substance (bad, neutral, or good), and any associated effects. RESULTS: Of 50
films reviewed, 34 (68%) displayed at least 1 episode of tobacco or alcohol use.
Twenty-eight (56%) portrayed 1 or more incidences of tobacco use, including all 7
films released in 1996 and 1997. Twenty-five films (50%) included alcohol use.
Smoking was portrayed on screen by 76 characters for more than 45 minutes in
duration; alcohol use was portrayed by 63 characters for 27 minutes. Good
characters use tobacco and alcohol as frequently as bad characters. Cigars and
wine are shown in these films more often than other tobacco or alcohol
substances. CONCLUSIONS: More than two thirds of animated children's films
feature tobacco or alcohol use in story plots without clear verbal messages of
any negative long-term health effects associated with use of either substance.
PMID- 10188669
TI - JAMA patient page: stroke.
PMID- 10188670
TI - Monoclonal gammopathies and associated skin disorders.
AB - The monoclonal gammopathies are characterized by clonal proliferation of plasma
cells and other clonally related cells in the B-cell lineage. These disorders
include monoclonal gammopathy of undetermined significance, multiple myeloma,
Waldenstrom macroglobulinemia, heavy chain diseases, plasmacytoma, and primary
amyloidosis. Many skin disorders have been described in association with
monoclonal gammopathies. This article provides an introduction to the definition,
detection, natural course, and spectrum of monoclonal gammopathies and a brief
discussion of pathogenesis. The article also reviews the skin disorders
associated with monoclonal gammopathies, categorizes the association, and
evaluates the strength of the association.
PMID- 10188671
TI - The misdiagnosis of malignant melanoma.
AB - Despite the increasing awareness of malignant melanoma over the last 40 years,
clinical diagnostic accuracy remains disappointing. Malignant melanoma can
masquerade clinically as benign lesions (false negatives), and benign pigmented
lesions can clinically simulate malignant melanoma (false positives). Histologic
examination of pigmented lesions is therefore important to ensure proper
diagnosis and treatment. We review many of the published reports of benign
lesions mimicking melanoma and melanoma masquerading as other entities as well as
present additional cases of clinical misdiagnoses of melanoma.
PMID- 10188672
TI - Cutaneous melanoma histologically associated with a nevus and melanoma de novo
have a different profile of risk: results from a case-control study.
AB - BACKGROUND: Histopathologic association between melanocytic nevus and melanoma
has been reported in approximately 10% to more than 50% of melanoma cases.
Whether melanomas in contiguity with a nevus have a different natural history and
pathogenesis from melanomas without a nevus is still to be determined. OBJECTIVE:
The present study was undertaken to clarify whether melanocytic nevus-associated
melanomas (MN[+]) have a different risk factor profile from cases without
histopathologic evidence of melanocytic nevus association (MN[-]). METHODS: The
study population consisted of 131 invasive melanoma cases with a thickness of
4.00 mm or less and 174 control cases without melanomas. The whole series was
evaluated for the following risk factors: phenotypic traits; the number of
common, atypical, and congenital nevus-like nevi; and freckling and history of
sunburns. Melanoma cases were revised for the presence of associated melanocytic
nevi. The analysis of risk factors was performed by a case-control approach
comparing cases, classified by histologic association with nevus, to the group of
controls. Possible differences in risk factor distribution between MN(+) cases
and MN(-) cases were evaluated with a polychotomous logistic regression model and
a likelihood ratio test for heterogeneity. RESULTS: Histopathologic association
between melanocytic nevus and melanoma was found in 27 cases (20.6%). Phenotypic
traits were shown to be more powerful predictors of risk for MN(-) than for MN(+)
cases (blond/red hair; odds ratio, 7.4 and 1.2, respectively; likelihood ratio
test for heterogeneity, 4.13; P < .05). Conversely, history of frequent sunburn
was a risk factor only in MN(+) cases (more than 5 sunburns; odds ratio, 6.7; 95%
confidence interval, 1.3-33.7), but not in MN(-) cases (odds ratio, 1.2; 95%
confidence interval, 0.3-4.0; likelihood ratio test for heterogeneity, 4.2; P <
.05). Where melanocytic nevi are concerned, an increased number of common nevi
was a predictor of melanoma risk in both MN(+) and MN(-) cases, but with a
different magnitude of risk, higher for MN(+) cases (number of common nevi, 10
30; odds ratio, 14.4 and 4.7, respectively; likelihood ratio test for
heterogeneity, 3.7; P = .055). CONCLUSION: This study showed that, although MN(+)
and MN(-) melanomas share many risk factors, there is a different strength of
association between the 2 groups. The effect of a history of sunburn as a
predictor of risk was found only for nevus-associated melanomas, suggesting a
possible role of sunburns in the neoplastic transformation of nevi.
PMID- 10188673
TI - Morphologic changes of pigmented skin lesions: a useful extension of the ABCD
rule for dermatoscopy.
AB - BACKGROUND: Epiluminescence microscopy (ELM) significantly increases the early
diagnosis of pigmented skin lesions (PSL) using established criteria and pattern
analysis. The ABCD rule for dermatoscopy (ie, ELM) provides a simplified approach
to the interpretation of ELM images on the basis of asymmetry (A), border (B),
color (C), and dermatoscopic structure (D). OBJECTIVE: We set out to determine
whether the diagnostic accuracy of the ABCD scoring algorithm can be
significantly improved by incorporating information about morphologic changes of
the lesion observed and provided by the patient. METHODS: We prospectively
collected 356 small pigmented skin lesions (< 1 cm) including 73 (20.5%)
melanomas. Before excision all patients were asked whether the lesion had changed
in size, color, or shape within the last year or whether they experienced any
sign of ulceration or spontaneous bleeding. ELM images of the lesions were
evaluated according to the ABCD rule for dermatoscopy to yield a semiquantitative
score. Accuracy of diagnosis was evaluated in terms of sensitivity, specificity,
and area under receiver operating characteristic curves (AUC). RESULTS: The
frequency of reported changes was significantly higher for melanomas than benign
PSL (65.8% vs 29.7%, P < .001). In a multivariate model morphologic change was a
significant independent predictor of malignancy (odds ratio = 3.17, 95%
confidence interval [CI]: 1.96 to 5.14, P < .001). The mean final score achieved
when using the enhanced ABCD-E criteria including morphologic change (E) was
significantly higher for melanomas (5.7, 95% CI: 5.3 to 6.0) than benign PSL
(2.9, 95% CI: 2.8 to 3.1, P < .001). Diagnostic accuracy was significantly higher
when the lesions were evaluated by the enhanced ABCD-E criteria as compared with
the standard ABCD score (AUC(ABCD) = 0.87 vs AUC(ABCD-E) = 0.90; P = .006).
CONCLUSION: Information about morphologic changes of PSL as reported by the
patient is a useful extension of the ABCD rule for dermatoscopy.
PMID- 10188674
TI - Participant satisfaction and value in American Academy of Dermatology and
American Cancer Society skin cancer screening programs in Massachusetts.
AB - BACKGROUND: More than 1 million Americans have attended the American Academy of
Dermatology's Melanoma/Skin Cancer Screening Programs since 1985. However, there
have been no reports of the participants' perceived value, satisfaction, and
benefits of skin cancer screening. OBJECTIVE: We attempted to measure the
benefits and subsequent screening practices of persons with presumptive positive
screening diagnoses. METHODS: A self-administered questionnaire was sent to
participants with positive screening diagnoses in Massachusetts. RESULTS: Of the
643 respondents, 81% rated their satisfaction as high and 84% had similar ratings
for the value of the screening. Screenings apparently led to an increase in self
screening (60% before screening compared with 84% after screening). CONCLUSION:
Although screening appears to have relatively strong benefits, further studies
should be conducted nationally.
PMID- 10188675
TI - The diagnostic yield in submitting nevi for histologic examination.
AB - BACKGROUND: Dermatologists have expertise in the clinical diagnosis of benign
melanocytic nevi. However, there are no data to confirm the accuracy of
diagnosis. Differences in the diagnostic accuracy between dermatologists and
nondermatologists with regard to cutaneous tumors has been infrequently studied.
OBJECTIVE: We examined the rate of malignant tumors occurring in lesions
submitted for routine microscopic examination that were clinically diagnosed as
benign melanocytic nevi. METHODS: We conducted a study at a regional, non
hospital-based dermatopathology laboratory using specimens submitted by
physicians of various specialties who were practicing in a 5-state Midwest region
of the United States. The preoperative and postoperative diagnoses were examined
on the basis of information provided by the clinician and of the subsequent
histopathologic diagnosis. A total of 7734 cutaneous pathology reports were
reviewed. Specimens submitted with a preoperative clinical diagnosis of mole or
nevus, with or without a modifier, were examined and compared with postoperative
microscopic diagnoses. RESULTS: Of 1946 specimens clinically diagnosed and
submitted as benign nevi, 45 (2.3%) were histologically diagnosed as malignant
tumors. This included 12 melanomas, 30 basal cell carcinomas, and 3 squamous cell
carcinomas. For specimens submitted by dermatologists, the rate of malignant
tumors increased when clinical information suggested findings beyond the classic
benign clinical presentation with the addition of modifiers such as irritated or
atypical, or if a malignancy was considered in the differential diagnosis (trend
for increasing clinical suspicion: P = .00002). Fewer dermatologists than
nondermatologists mistook a malignant tumor for a benign nevus (1.3% vs 3.8%, P =
.003). CONCLUSION: Our data document that 2.3% of clinically diagnosed benign
nevi were microscopically diagnosed as malignant tumors. Whether this malignancy
rate in clinically diagnosed, benign, melanocytic nevi is above or below the
threshold to establish a policy for submission for histopathologic examination
remains to be determined as a collective societal and medical professional
responsibility.
PMID- 10188676
TI - A population-based survey on the use of artificial tanning devices in the
Province of Quebec, Canada.
AB - BACKGROUND: The suntanning industry has grown up over the last decade in North
America, mainly because tanned skin is socially desirable and artificial tanning
is perceived as a "safe tan." However, exposure to UV radiation is known to cause
adverse health effects. OBJECTIVE: The purpose of this study was to estimate the
prevalence of use of tanning equipment in the Province of Quebec and to
characterize people who reported using these devices. METHODS: In 1996, a
telephone survey was carried out among adults from the two most densely populated
regions (Montreal, Quebec) of the Province of Quebec. The final sample included
1003 white persons 18 to 60 years old. Interviewers used a standardized
questionnaire to document the characteristics of the participant, skin phototype,
and exposure habits to artificial UV radiation sources. RESULTS: During the last
5 years before the survey, 20.2% of the respondents reported they had used, at
least once, a tanning device in a commercial tanning salon. The rate of use
during the last 12 months before the study was 11.1%. A significantly higher
proportion of female, young people (18 to 34 years old) and single persons was
found among tanning bed users. Twenty-six percent of users experienced one or
more acute adverse health effects from the artificial UV irradiation. Most of
these were cases of skin burns. A high proportion (77.5%) of those who used
tanning equipment during the last year before the study said they would return to
tanning salons. The intention of returning to a tanning salon was not influenced
by the occurrence of the acute adverse health effects. The most prevalent reason
given for using tanning equipment was "to improve their appearance by a tan."
Most people (60.4%) who used a tanning bed during the last 5 years before the
study believe that tanning salons are not dangerous. CONCLUSION: This survey
indicates that tanning bed use is very prevalent in the Province of Quebec,
mainly among young women. The high rate of acute adverse health effects related
to artificial tanning, particularly skin burns, is of concern. Finally, our
results underline the importance of changing attitudes and beliefs in the
population regarding artificial tanning.
PMID- 10188677
TI - Long-term application of extracorporeal photochemotherapy in severe atopic
dermatitis.
AB - BACKGROUND: Extracorporeal photochemotherapy (ECP) using UVA irradiation of
enriched leukocytes in the presence of methoxsalen as a photoactivatable
substrate has been employed for the treatment of several immunologically mediated
disorders. OBJECTIVE: Our purpose was to determine the efficacy and safety of
long-term ECP in the treatment of severe atopic dermatitis. METHODS: Fourteen
patients with severe recalcitrant atopic dermatitis were treated with ECP in an
open clinical trial at 2-week intervals. Disease activity was scored before each
ECP cycle by means of a standardized protocol. RESULTS: A complete clinical
remission was achieved in 4 patients (29%). Five patients (36%) experienced a
substantial response with reduction of skin inflammation by at least 75%, whereas
in one patient (7%) disease activity was reduced by more than 50%. Four patients
were withdrawn from the study for unresponsiveness. No clinical signs of
immunosuppression or other severe adverse events became evident. CONCLUSION: Long
term ECP may have significant beneficial effects on the course of atopic
dermatitis and should therefore be considered as a treatment modality for
patients suffering from severe and otherwise refractory atopic skin disease.
PMID- 10188678
TI - Contact leukomelanosis induced by the leaves of Piper betle L. (Piperaceae): a
clinical and histopathologic survey.
AB - BACKGROUND: In April 1997, an unusual pigmentary disorder was noticed by
dermatologists in Taiwan. All patients had a history of using facial dressings
with steamed leaves of Piper betle L. (Piperaceae). OBJECTIVE: Our purpose was to
clarify the evolution and the origin of this unique leukomelanosis. METHODS:
Fifteen patients with an unusual pigmentary disorder, who visited our clinic in
September and October 1997, were asked to complete a questionnaire designed to
elicit the history related to the disorder. Eight of these 15 patients underwent
skin biopsies: 6 on the mottled hyperpigmented area (group A) and 2 on the
hypopigmented area (group B). All 8 specimens were prepared with hematoxylin
eosin, Masson-Fontana, and S-100 stains. RESULTS: The results of the
questionnaire revealed that these patients had all experienced a temporary
erythematous reaction in the first few days of the use of the facial dressing,
and 9 of them also complained of an accompanying stinging sensation. A bleaching
effect became noticeable approximately 1 week to 1 month later. Eight patients
reported that the hyperpigmentation and confetti-like hypopigmentation occurred
after overexposure to the sun. In both groups, histopathologic examination
revealed some melanophages in the dermis. Masson-Fontana staining of specimens
from group A showed local interspersed depigmentation and hyperpigmentation in
the basal epidermis and pigmentary incontinence in the dermis. This picture was
different from the homogeneous depigmentation within basal epidermis in specimens
from group B. In both groups, S-100 staining was negative for melanocytes in the
depigmented area. CONCLUSION: The clinical course and histopathologic findings
suggest that the evolution of this pigmentary disorder can be divided into 3
stages. The first stage is the immediate bleaching stage, when an irritant
reaction is usually conspicuous. The second stage consists of prominent
hyperpigmentation visible both grossly and microscopically. The final stage is
characterized by confetti-like depigmentation. It may be induced by chemicals in
the betel leaves such as phenol, catechol, and benzene derivatives, perhaps
through inhibition of melanin synthesis or melanocytotoxicity.
PMID- 10188679
TI - Experimentally induced chronic irritant contact dermatitis to evaluate the
efficacy of protective creams in vivo.
AB - BACKGROUND: Widely accepted in vivo models to evaluate the efficacy of protective
creams (PCs) are still missing. OBJECTIVE: The effect of petrolatum's ability to
protect against irritation was tested in a repetitive irritation test to optimize
the concentration of irritants against which PCs are tested and to evaluate the
necessary cumulative application time. METHODS: On 20 healthy volunteers, the
irritants (sodium lauryl sulfate 5% vs 10%, sodium hydroxide 0.5% vs 1%, lactic
acid 20% vs 30%, and toluene undiluted) were applied daily for 2 weeks on the
ventral forearms after 30 minutes of pretreatment with petrolatum. The irritant
cutaneous reactions were quantified by erythema score, transepidermal water loss,
and chromametry. RESULTS: For petrolatum, a significant protective effect was
obtained against irritation by sodium lauryl sulfate, sodium hydroxide, and
toluene in different degrees. Less efficacy was observed against lactic acid.
CONCLUSION: It was concluded that a 1-week period of cumulative irritation is
enough to evaluate the efficacy of PCs against most irritants, even if lower
concentrations of irritants are used.
PMID- 10188680
TI - The cumulative incidence of atopic dermatitis in the first 12 months among
Chinese, Vietnamese, and Caucasian infants born in Melbourne, Australia.
AB - BACKGROUND: Atopic dermatitis (AD), a disease with both inherited and
environmental components determining its clinical expression, has been reported
to be more frequent in people of Asian origin. OBJECTIVE: Our purpose was to
compare the 12-month cumulative incidence of AD in Caucasian, Chinese, and
Vietnamese babies born in Australia. METHODS: Sixty-two Caucasian, 61 Chinese,
and 59 Vietnamese babies born in Melbourne, Australia were examined soon after
birth and then followed up for 12 months to assess the frequency of AD. Parental
education, employment history, and housing conditions were also recorded.
RESULTS: AD developed in 21% of Caucasians, 44% of Chinese, and 17% of Vietnamese
infants. Parents of the Chinese and Caucasian infants had similar socioeconomic
and housing conditions compared with the parents of the Vietnamese infants, who
tended to be of lower socioeconomic status with communal housing and lack of
plush-pile carpeting. CONCLUSION: The high incidence of AD in Chinese compared
with Caucasian infants tends to reflect genetic differences between the two
populations, whereas the difference in incidence between the Chinese and
Vietnamese infants possibly reflects more the environmental contribution to
disease expression.
PMID- 10188681
TI - A clinical and histologic prospective controlled comparative study of the
picosecond titanium:sapphire (795 nm) laser versus the Q-switched alexandrite
(752 nm) laser for removing tattoo pigment.
AB - BACKGROUND: Theory predicts that picosecond lasers should be more effective than
the currently available nanosecond lasers in removing tattoo ink. In addition to
thermal confinement, such pulse widths cause optimal photomechanical disruption
of the target. OBJECTIVE: This study compared the efficacy of the picosecond
titanium:sapphire (795 nm, 500 psec) laser and the Q-switched alexandrite (752
nm, 50 nsec) laser in the treatment of tattooed guinea pigs. METHODS: Six albino
guinea pigs, each with 6 uniformly 1 cm circular black tattoos, were treated.
Three of the tattoos were divided into 2; one half was treated with the
titanium:sapphire laser and the other half with the alexandrite laser. Fluences
used for both lasers were 6.11, 4.24, and 2.39 J/cm2 with spot sizes of 1.25,
1.5, and 2 mm, respectively. The remaining spots served as control. Clinical
evaluation and biopsies were performed at baseline and at 11 and 16 weeks after a
single laser treatment. RESULTS: Greater clearance of tattoo was observed in
titanium:sapphire laser-treated areas in 2 of the 4 surviving guinea pigs. In
some areas total clearing was observed after the single titanium:sapphire laser
treatment. Clearing improved with higher fluences. No scarring was present.
Histologic results showed similar findings. CONCLUSION: Our findings suggest that
the picosecond titanium:sapphire laser is more effective than the Q-switched
alexandrite laser in removing tattoo pigment and may be of significant clinical
utility.
PMID- 10188682
TI - An open study of tissue adhesive in full-thickness skin grafting.
AB - BACKGROUND: Securing full-thickness skin grafts (FTSG) by suturing is a time
consuming procedure, even in experienced hands. The advent of tissue adhesives
has led to their use in a variety of surgical procedures, providing an acceptable
alternative to conventional suturing. OBJECTIVE: Our purpose was to identify
whether the tissue adhesive n-butyl-2-cyanoacrylate (NBCA) can be used to secure
FTSG and to compare the outcome with conventional suturing. METHODS: Twenty-one
patients with defects after Mohs micrographic surgery were enrolled into the
study. An initial pilot study of 8 patients compared NBCA and sutures within
individual grafts; the subsequent 13 patients had grafts secured with between 4
and 8 cardinal sutures and NBCA alone. RESULTS: No differences in healing,
complications, or cosmetic appearance were observed between the sides secured
with NBCA and with sutures in the pilot study. Of the grafts in the subsequent 13
patients, 2 patients experienced superficial necrosis with subsequent healing and
a good cosmetic outcome, the remainder healed in place without complications,
with excellent cosmetic outcome. CONCLUSION: NBCA is suitable for securing
selected FTSG and provides a significant time-saving over the traditional
approach of suturing such grafts into place.
PMID- 10188683
TI - Low-dose oral methotrexate treatment for recalcitrant palmoplantar pompholyx.
AB - We describe 5 patients with severe pompholyx who did not respond to conventional
therapy or who had debilitating side effects from corticosteroids. Low-dose
methotrexate was added to their treatment regimens and led to significant
improvement or clearing with a favorable side-effect profile. In all 5 patients
the need for oral corticosteroid therapy was substantially decreased or
eliminated, thus decreasing potential corticosteroid-induced morbidity. In this
uncontrolled series of patients with recalcitrant palmoplantar pompholyx,
methotrexate was an effective treatment and acted as a steroid-sparing agent.
PMID- 10188684
TI - Depth of vaporization and the effect of pulse stacking with a high-energy, pulsed
carbon dioxide laser.
AB - BACKGROUND: Laser resurfacing of photodamaged skin has become popular, but
questions regarding its safety with regard to the risks of scarring have arisen.
OBJECTIVE: This study was designed to investigate the depth of vaporization and
residual thermal necrosis of single-pulse vaporization and multiple passes versus
pulse-stacking and multiple passes. The potential significance of operator
technique and laser parameters is considered. METHODS: Skin samples from surgical
excisions were treated by means of a Coherent Ultrapulse carbon dioxide laser at
250 mJ per pulse and 500 mJ per pulse with a 3 mm collimated beam and a
repetition rate of 10 Hz. A total of 70 treatment areas were performed. Blinded
analysis of the histologic effects of single-pulse, double-pulse, and triple
pulse vaporization after 1 through 10 passes was undertaken. RESULTS: A plateau
of vaporization was observed after 3 passes at both 250 and 500 mJ whether single
, double-, or triple-pulse vaporization was used. This plateau occurs at
approximately 100 to 250 microm from the skin surface. Thermal necrosis is well
controlled only with single-pulse vaporization. There is a direct linear increase
in the depth of thermal necrosis both with the number of pulses stacked and the
number of passes. CONCLUSION: Pulsed carbon dioxide laser resurfacing is a safe
and self-limited procedure if a pulse width of less than 1 msec is used with
single-pulse vaporization and fluences of 3.5 J/cm2 and 7.0 J/cm2. There appears
to be little justification for performing more than 3 or 4 passes. Pulse stacking
may significantly increase residual thermal necrosis, thereby increasing the risk
of scarring. Operator technique may be significant in avoidance of this
occurrence.
PMID- 10188686
TI - Dermatologic(al) sesquipedalianism.
PMID- 10188685
TI - The power of prevention.
PMID- 10188688
TI - HPV 18-induced pigmented bowenoid papulosis of the neck.
AB - We describe the case of a 53-year-old man in whom pigmented bowenoid papulosis
developed on the skin of the neck. By polymerase chain reaction with general
primers for genital human papillomaviruses (HPV) and subsequent restriction
enzyme cleavage we could demonstrate HPV 18-related DNA in two biopsy specimens
of the pigmented papules. To our knowledge, this report represents the first case
of HPV 18-induced extragenital bowenoid papulosis of the neck.
PMID- 10188691
TI - Primary adenoid cystic carcinoma of skin with lung metastasis.
AB - Primary cutaneous adenoid cystic carcinoma was first reported in 1975. We report
a case of this malignancy with pulmonary metastases in a 70-year-old man and
offer a brief review of the literature.
PMID- 10188690
TI - Anti-epiligrin cicatricial pemphigoid with IgG autoantibodies to the beta and
gamma subunits of laminin 5.
AB - Anti-epiligrin cicatricial pemphigoid is an autoimmune subepithelial blistering
disorder of mucous membranes and skin. By immunoblot analyses, sera of most
patients with antiepiligrin cicatricial pemphigoid have been shown to react
specifically with the alpha3 chain of laminin 5. We describe the first patient
with anti-epiligrin cicatricial pemphigoid in whom circulating IgG autoantibodies
directed against the beta3 and gamma2-chains of laminin 5 were detected.
Treatment with oral prednisolone was beneficial in controlling the disease.
PMID- 10188687
TI - Clinical pearl: accentuated transverse hallucal skin crease--a cutaneous skin
marker for hallux rigidus (osteoarthritis of the big toe joint).
PMID- 10188693
TI - Vitiligo: phototherapeutic options.
PMID- 10188692
TI - Chemotherapy-induced inflammation in seborrheic keratoses mimicking disseminated
herpes zoster.
AB - We report a rare instance of chemotherapy-induced seborrheic keratoses of Leser
Trelat in a patient with acute leukemia. In addition, this is the first known
case to mimic disseminated herpes zoster.
PMID- 10188694
TI - Pyrazinamide-induced lichenoid photodermatitis.
PMID- 10188689
TI - Protease inhibitor-induced lipodystrophy.
AB - The development of lipodystrophy as evidenced by central obesity, "moon facies,"
and a "buffalo hump" is a classical feature of Cushing's disease. Recently an
association of "lipodystrophy" with the use of protease inhibitors has been
reported. We describe a patient with lipodystrophy secondary to protease
inhibitor therapy for HIV infection.
PMID- 10188700
TI - The Emanuel Miller Memorial Lecture 1998. Autism: two-way interplay between
research and clinical work.
AB - The two-way interplay between research and clinical practice in relation to
autism is reviewed with respect to: (1) diagnosis and syndrome delineation; (2)
the nature of the disorder: (3) intervention studies; and (4) aetiology, as
manifest during four time periods; (a) the 1950s and 1960s; (b) the 1970s into
the mid 1980s; (c) the late 1980s and early 1990s; and (d) the late 1990s. It is
concluded that clinical practice has changed out of all recognition during the
last 50 years and that research findings have been crucial in bringing about that
change. It has not, however, been a one-way traffic. Many key advances were
prompted by astute clinical observations and some extravagant research claims
were given a more balanced perspective through the light of clinical experience.
Crucial research and clinical tasks remain but the means to meet them are there
if the opportunities are taken and attention is paid to the lessons of the past.
PMID- 10188697
TI - Lichen nitidus and dinitrochlorabenzene.
PMID- 10188695
TI - Eruptive melanocytic nevi and cherry angiomas secondary to exposure to sulfur
mustard gas.
PMID- 10188699
TI - The assessment and treatment of deaf children with psychiatric disorders.
AB - The assessment and treatment of deaf children with psychiatric disorder is
intimately related to the individual child's communication, which in turn is
affected by a number of factors, medical, social, and cultural. The deafness can
be aetiologically related to the psychiatric disorder or can be incidental.
Treatment strategies should be adapted to meet the individual child and family's
needs. Deaf professionals have a vital role in mental health services for this
population. The use of an interpreter can clarify communication and cultural
issues for deaf and hearing children, families, and professionals.
PMID- 10188696
TI - Zosteriform distribution of acantholytic dyskeratotic epidermal nevus?
PMID- 10188698
TI - Children's reading levels.
PMID- 10188701
TI - Generating novel ideas: fluency performance in high-functioning and learning
disabled individuals with autism.
AB - Tasks of fluency tap the ability to generate multiple responses spontaneously
following a single cue or instruction. The present study compared the fluency
performance of subjects with autism and clinical control subjects at two
different levels of ability (high-functioning subjects with a verbal IQ of 76 or
greater, and globally learning disabled subjects with a verbal IQ of 74 or
below). A battery of tasks was employed to assess subjects' word fluency (for
letters and semantic categories), ideational fluency (for uses of objects and
interpretations of meaningless line drawings), and design fluency (for abstract
meaningless designs). Subjects with autism showed reduced fluency for both the
word and ideational fluency tasks, generating significantly fewer responses than
the clinical control subjects. Results were particularly striking for the
ideational fluency tasks. On these tasks, autistic subjects produced very low
response totals, with the performance of the high-functioning subjects with
autism equivalent to that of the learning disabled subjects with autism and
significantly inferior to that of the learning disabled control individuals. In
contrast, the results of the design fluency paradigm paint a different picture.
This paradigm revealed no significant difference in the quantity of designs
generated by the subjects with autism and the control subjects but a clear
qualitative difference, with the autistic group producing significantly higher
rates of disallowed and perseverative responses. Whilst the results of the word
and ideational fluency tasks are suggested to support the hypothesis that
individuals with autism are impaired in the generation of novel responses and
behaviour, the results of the design fluency task are equally consistent with an
impairment in the regulation of behaviour through inhibition and/or monitoring.
The implications of these findings for the study of executive function abilities
in autism are discussed.
PMID- 10188702
TI - Perceptual processing among high-functioning persons with autism.
AB - Two tasks were used to assess the processing of whole versus parts of objects in
a group of high-functioning children and adolescents with autism (N = 11) and a
comparison group of typically developing peers (N = 11) matched for chronological
age and IQ. In the first task, only the children with autism showed a global
advantage, and the two groups showed similar interference between levels. In the
second task, the children with autism, despite longer RTs, showed similar
performance to the comparison group with regard to the effect of goodness on
visual parsing. Contrary to expectations based on the central coherence and
hierarchisation deficit theories, these findings indicate intact holistic
processing among persons with autism. The implications of these findings are
discussed in relation to apparently discrepant evidence from other studies.
PMID- 10188703
TI - The prevalence of Gilles de la Tourette's syndrome in children and adolescents
with autism.
AB - Thirty-seven pupils attending a special school for children and adolescents with
autism were observed for the presence of motor and vocal tics. Subsequent family
interviews confirmed the diagnosis of comorbid Gilles de la Tourette's Syndrome
(GTS) in three children with autism, giving a minimum prevalence rate of 8.1 %.
Family history data also suggested this was heritable. The presence of GTS was
not associated with superior intellectual, language, or social development.
Results suggest that the rate of GTS in autism may exceed that expected by
chance. The limited sample size constrains this conclusion. A large-scale
epidemiological study testing this association study would appear merited.
PMID- 10188704
TI - Can autism be diagnosed accurately in children under 3 years?
AB - This study investigated the reliability and stability of an autism diagnosis in
children under 3 years of age who received independent diagnostic evaluations
from two clinicians during two consecutive yearly evaluations. Strong evidence
for the reliability and stability of the diagnosis was obtained. Diagnostic
agreement between clinicians was higher for the broader discrimination of autism
spectrum vs. no autism spectrum than for the more specific discrimination of
autism vs. PDD-NOS. The diagnosis of autism at age 2 was more stable than the
diagnosis of PDD-NOS at the same age. Social deficits and delays in spoken
language were the most prominent DSM-IV characteristics evidenced by very young
children with autism.
PMID- 10188705
TI - Adolescent depression: social network and family climate--a case-control study.
AB - In a study of a total high-school population, 2300 students aged 16-17 years were
screened for depression (BDI, CES-DC). Those with a self-evaluation indicating
depression, together with controls matched for sex, age, and class were
interviewed (DICA-R-A). The 177 pairs, where both individuals were interviewed
and the control had no lifetime diagnosis of depression, were analysed in the
form of paired differences for psychosocial factors and compared within
diagnostic groups. The psychosocial factors were measured with the ISSI subscales
and six attitude questions about family climate (KSP). Adolescents with an
episode of major depression during part of the last year did not differ from
their controls. Those with long-lasting depressive symptoms, i.e. dysthymia with
or without episodes of major depression, had a more limited social interaction
and were not satisfied with it. They also evaluated their family climate and
attachment network as being more inadequate than did their controls. Depressed
adolescents with comorbid conduct disorder had a more negative evaluation of
availability and adequacy of both social interaction and attachment network than
their controls. This group had a very negative view of their family climate.
Since this is a case-control study conclusions cannot be drawn about cause and
effect.
PMID- 10188707
TI - The role of maternal cognitions in infant sleep problems as assessed by a new
instrument, the maternal cognitions about infant sleep questionnaire.
AB - Sleeping problems in young children are very common, affecting up to 20% of 1
year-olds. Behaviour therapy is the most widely recognised treatment but a
significant proportion of parents find it aversive. This suggests that parental
cognitions may be important and underevaluated. The aims of this study were
therefore fourfold: (1) to describe the development of a new tool to measure
maternal cognitions in relation to infant sleeping problems, the Maternal
Cognitions about Infant Sleep Questionnaire (MCISQ): (2) to assess the
psychometric properties of the MCISQ; (3) to test the hypothesis that maternal
cognitions will be associated with, and specific to, infant sleep problems; and
(4) to discuss the implications of the findings with respect to aetiological
models of infant sleep problems, treatment, and future research. Results showed
that maternal cognitions about setting limits, anger at the infant's demands, and
doubts about parenting competence were significantly associated with infant sleep
problems, whereas cognitions about infant hunger or cot death were not. It is
hypothesised that these cognitive responses, if extreme, may disrupt sensitive
parent-child interactions, which over time could lead to impairments in the
development of infant self-regulation.
PMID- 10188706
TI - Intrusive and withdrawn behaviours of mothers interacting with their infants and
boyfriends.
AB - Investigated stability and change in intrusive and withdrawn interaction
behaviours of 23 mothers in Study 1 and 31 mothers in Study 2. Comparisons
between mother-infant and mother-boyfriend interactions revealed that mothers who
had been withdrawn with their infants were quiet, bored-looking, physically
distant, and underinvolved with their boyfriends. Mothers who had been intrusive
with their infants were verbally sharp and controlling with their boyfriends.
These findings suggested stability across social contexts. Comparing maternal
responding to instructions to think about themselves (self-focus) or their
infants (infant-focus) revealed that infant-focusing attenuated intrusive
behavior among intrusive mothers and self-focusing attenuated negative affect
among withdrawn mothers. These findings suggested that cognitive focusing
ameliorates nonoptimal maternal behaviours and has differential effects on
intrusive and withdrawn mothers.
PMID- 10188708
TI - Psychosocial adversities underestimated in hyperkinetic children.
AB - Abnormal psychosocial factors, assessed both clinically and by raters blind to
clinical presentation, were examined in 21 hyperkinetic and 26 conduct disordered
children. Blind raters found the frequency of psychosocial adversities to be
similar in the two disorders. By contrast the clinical rater, who did know the
diagnosis of patients, rated adverse psychosocial situations as much lower in
hyperkinetic children than in children with conduct disorder. Logistic regression
showed, particularly in the category of abnormal intrafamilial relationships
(Lack of warmth in parent child relationship, Hostility or scapegoating of the
child, Intrafamilial discord among adults), effects of the interaction between
rater and knowledge of diagnosis. Clinical raters should be aware of abnormal
psychosocial situations in hyperkinetic children and assess possible adverse
effects on parents and children. Researchers should be aware of a possible bias
in research interviews.
PMID- 10188709
TI - DSM-IV AD/HD: confirmatory factor models, prevalence, and gender and age
differences based on parent and teacher ratings of Australian primary school
children.
AB - Based on parent and teacher ratings of primary school children on a scale
comprising the 18 DSM-IV AD/HD symptoms, this study used confirmatory factor
analysis to compare three models: all items in one factor; inattention in one and
hyperactivity and impulsivity items in a separate factor; and inattention,
hyperactivity, and impulsivity items in three separate factors. It also examined
the prevalence rates of the three AD/HD Types, and gender and age differences.
Results supported both the two- and three-factor models, with the three-factor
model only slightly better than the two-factor model. Based on parent-teacher
agreement, the prevalence rates were 1.6, 0.2 and 0.6% for the Inattentive,
Hyperactive-Impulsive, and Combined Types, respectively. Overall, the male to
female ratio was 5: 1, and boys were rated higher than girls by both parents and
teachers. Age differences were minimal. The implications of the findings in
relation to some of the assumptions made in DSM-IV for AD/HD are discussed.
PMID- 10188710
TI - Effortful and automatic information processing in boys with ADHD and specific
learning disorders.
AB - Boys with Attention Deficit Hyperactivity Disorder (ADHD, N = 50), Specific
Learning Disorder (LD, N = 45), combined Specific Learning Disorder and ADHD
(LD/ADHD, N = 25), and controls (N = 51) completed effortful and automatic
information processing tasks based on Treisman and Gelade's (1980) "information
integration theory". ADHD and LD/ADHD subjects did not differ from controls at
baseline or under feedback and reward conditions, suggesting that they were
investing similar levels of mental effort in the tasks. The LD group had a
superior performance in the effortful task and an inferior performance in the
automatic task compared with the other groups at baseline. The data suggest a
potential method of distinguishing primary LD from learning difficulties that
occur secondary to ADHD.
PMID- 10188711
TI - On diagnosing rare disorders rarely: appropriate use of screening instruments.
AB - The main aim of this study was to determine whether child mental health
professionals who regularly use questionnaires to screen for mental disorders
know that these questionnaires have a low predictive value when the base rate of
a disorder is low. The study was based on a representative sample of
professionals who used questionnaires regularly to screen for mental disorders.
They were set a problem in which a clinic sample was screened with a
questionnaire that, at a certain cut-point, had 80 % sensitivity and 80 %
specificity, and in which the true base rate of disorder was 10%. Only 10% (5/48)
of respondents answered correctly that just 30 % of individuals who scored above
this cut-point would actually have the disorder and more than half of respondents
believed that 80 % would have the disorder. Both users and designers of
questionnaires need to be more aware of and explicit about their drawbacks as
screens for mental disorders.
PMID- 10188712
TI - The effect of methylphenidate and clonidine on response inhibition and state
regulation in children with ADHD.
AB - The goal of this study was to evaluate the effect of methylphenidate (MPH) and
clonidine in comparison with placebo on response inhibition and state regulation
in children with Attention Deficit Hyperactivity Disorder (ADHD). The study
utilised a double-blind cross-over design in which children were randomly
assigned without replacement to placebo, MPH, and clonidine following baseline
assessment. The primary dependent measures were derived from children's
performance (reaction time and errors) on a GO-NO GO task under three conditions
that altered the inter-stimulus interval (ISI) for presented GO-NO GO stimuli:
ISI of 1 sec (fast condition), 4 sec (medium condition), and 8 sec (slow
condition). Findings indicated no difference in task performance between groups
treated for 7 weeks with placebo, MPH, and clonidine. We concluded that the state
regulation problem in ADHD is resistant to MPH and clonidine.
PMID- 10188713
TI - The psychological development of children from Belarus exposed in the prenatal
period to radiation from the Chernobyl atomic power plant.
AB - This study examined psychological development in 138 children at the age of 6-7
and 10-11 years, who had suffered prenatal radiation exposure at the time of the
Chernobyl accident in 1986. These children were compared to a control group of
122 children of the same age from noncontaminated areas of Belarus. The
examination included neurological and psychiatric examination, intellectual
assessment, and clinical psychological investigation of parents as well as the
estimation of thyroid exposure in utero. The exposed group manifested a relative
increase in psychological impairment compared with the control group, with
increased prevalence in cases of specific developmental speech-language disorders
(18.1% vs. 8.2% at 6-7 years; 10.1% vs. 3.3% at 10-11 years) and emotional
disorders (20.3% vs. 7.4% at 6-7 years; 18.1 vs. 7.4% at 10-11 years). The mean
IQ of the exposed group was lower than that of the control group, and there were
more cases of borderline IQ (IQ = 70-79) (15.9% vs. 5.7% at 6-7 years; and 10.1%
vs. 3.3% at 10-11 years). The mean value of thyroid doses from 131I 0.4 Gy was
estimated for children exposed in utero. No correlation was found between
individual thyroid doses and IQ at age 6-7 years or 10-11 years. We notice a
positive moderate correlation between IQ of children and the educational level of
their parents. There was a moderate correlation between high personal anxiety in
parents and emotional disorders in children. We conclude that a significant role
in the genesis of borderline intellectual functioning, specific developmental
disorders of speech, language and scholastic skills, as well as emotional
disorders in the exposed group of children was played by unfavourable social
psychological and social-cultural factors such as a low educational level of
parents, the break of microsocial contacts, and adaptational difficulties, which
appear following the evacuation and relocation from the contaminated areas.
PMID- 10188714
TI - Vasoactive intestinal peptide (VIP) and VIP receptors: gene expression and growth
modulation in medulloblastoma and other central primitive neuroectodermal tumors
of childhood.
AB - Vasoactive intestinal peptide (VIP) is a neuromodulator and growth regulator in
the developing nervous system. We analyzed 10 primitive neuroectodermal tumor
(PNET) cell lines, 29 central PNET (cPNET) and 17 tumors of the Ewing's
sarcoma/peripheral PNET family (ESFT) using reverse transcriptase-polymerase
chain reaction (RT-PCR) and Southern hybridization. Each of the 10 cell lines and
86.2% of cPNET expressed mRNA for VIP receptor 1 (VIPR1) compared to 52.9% of
ESFT. VIPR2 was expressed in 75.8% of cPNET, in 28.6% of ESFT and in all 10 cell
lines. cPNET demonstrated high-affinity binding of 125I-VIP on quantitative
autoradiography and in competitive binding assays. VIP inhibited tumor cell
proliferation in a dose-dependent manner in 5 of 7 PNET cell lines. We conclude
that VIPR1 and VIPR2 are highly expressed in cPNET and demonstrate that VIP is a
growth modulator in these tumors.
PMID- 10188715
TI - Dietary fiber and plant foods in relation to colorectal cancer mortality: the
Seven Countries Study.
AB - Many observational studies have found that higher consumption of vegetables, and
to a lesser extent of fruits, was associated with lower risk of colorectal
cancer. In particular, fiber or foods high in fiber have received attention in
the potential prevention of colorectal cancer. We performed an ecological
analysis with data of the Seven Countries Study, to investigate whether intake of
fiber and plant foods contributes to cross-cultural differences in 25-year
colorectal-cancer mortality in men. In the Seven Countries Study, around 1960
12,763 men aged 40 to 59 were enrolled in 16 cohorts in 7 countries. Baseline
dietary information was gathered in small random samples per cohort, and nutrient
intakes were based on chemical analyses of the average diets per cohort. Crude
and energy-adjusted mortality-rate ratios were calculated for a change of 10% of
the mean intake of fiber and plant foods, i.e., total plant foods, fruits,
vegetables, potatoes, grains, and related sub-groups. Fiber intake was inversely
associated with colorectal-cancer mortality with an energy-adjusted rate ratio of
0.89 (95% confidence interval 0.80-0.97). An increase of 10 gram of daily intake
of fiber was associated with a 33% lower 25-year colorectal-cancer mortality
risk. Intakes of vitamin B6 [0.84 (0.71-0.99)] and alpha-tocopherol [0.94 (0.89
0.99)] were also inversely associated with risk. Consumption of plant foods and
related sub-groups was not related to colorectal cancer. It appears that fiber
intake best indicates the part of plant food consumption, including whole grains,
that is relevant for lowering colorectal cancer risk.
PMID- 10188716
TI - Constitutive and conditional cadherin expression in cultured human ovarian
surface epithelium: influence of family history of ovarian cancer.
AB - Epithelial ovarian carcinomas arise in a simple mesothelium (ovarian surface
epithelium, OSE) but exhibit properties of oviductal and endometrial epithelia.
Thus, during malignant progression, their differentiation proceeds from simple to
complex, in contrast to carcinomas in other tissues. Related changes in OSE of
women with a history of familial ovarian cancer indicate that this aberrant
differentiation is initiated very early in neoplastic progression. The mechanisms
underlying this process are not understood. Because cadherins are known
regulators of differentiation, we investigated the relationship of the cadherins
E, N and P to OSE morphology, growth patterns and differentiation in cultures of
normal and metaplastic OSE from women with (FH-OSE) and without (NFH-OSE) a
family history of ovarian cancer and in the ovarian carcinoma lines OVCAR-3 and
CaOV3. We used immunofluorescence, RT-PCR, in situ hybridization and Western
blotting. Our results define N-cadherin as the constitutively expressed cadherin
of normal and metaplastic OSE and indicate that P-cadherin is undetectable while
E-cadherin expression is conditional and related to genotype, stage of neoplastic
progression and growth pattern. The altered expression of E-cadherin in
apparently normal OSE of women with hereditary ovarian cancer syndromes in
conjunction with the known capacity of E-cadherin to induce epithelial
characteristics implicates this adhesion molecule as a possible inducer of the
aberrant Mullerian differentiation which characterizes epithelial ovarian
carcinomas. Abnormal differentiation in such (pre)-neoplastic tissues may
represent an early, irreversible, non-mutational step in ovarian epithelial
neoplastic progression.
PMID- 10188717
TI - Human herpesvirus 8 primary infection occurs during childhood in Cameroon,
Central Africa.
AB - While in the United States and northern Europe, human herpesvirus 8 (HHV-8)
appears to be mainly sexually transmitted with primary infection occurring in
adulthood, the modes of transmission remain unknown in East and Central Africa,
where Kaposi's sarcoma (KS) is a long-standing endemic disease, occurring not
only in adults but also in children. The aim of our present study was to
determine the prevalence of HHV-8 infection in children from Yaounde, Cameroon,
Central Africa. Specific antibodies directed against both latent and lytic HHV-8
antigens were detected and titrated, with an immunofluorescence assay using the
KS-1 cell line, in the plasma of 258 children and adolescents, of 32 mother and
child pairs and of 189 pregnant women. Two different HHV-8 DNA-specific sequences
were searched in the buffy coat by PCR assays. The overall HHV-8 seroprevalence
was 27.5% among these children and adolescents. In newborns, seroprevalence
reached 46%, reflecting passive transmission of maternal IgG. This was followed
by a marked drop. Then, beginning around 4 years of age, a regular increase of
HHV-8 antibodies took place, reaching 39% in the 12- to 14-year age group and 48%
above 15 years, a rate similar (54.5%) to that observed in pregnant women. PCR
detection of HHV-8 sequences was negative in seronegative children and positive
in the buffy coat in 17% of HHV-8-seropositive children, reflecting a low viral
load in the peripheral blood. Our results establish that in Central Africa HHV-8
infection takes place during childhood by casual routes, in contrast to the
sexual transmission observed in adults in northern Europe and the United States.
We hypothesize that the lymphadenopathic form of KS seen in African children is
related to an early and massive infection by HHV-8 in susceptible individuals.
PMID- 10188718
TI - Selection of carbohydrate antigens in human epithelial ovarian cancers as targets
for immunotherapy: serous and mucinous tumors exhibit distinctive patterns of
expression.
AB - Expression of blood group-related carbohydrate antigens was examined in frozen
sections from a series of ovarian carcinomas of different histological types
using an indirect immunoperoxidase technique. Antigenic specificities belonging
to the O(H) and Lewis blood group families (H-1, H-2, Le(a), sLe(a), Le(x),
sLe(x), Le(b) and Le(y)) or the mucin-core family (Tn, sTn and TF) were studied.
A distinct difference in antigen expression between mucinous and other ovarian
carcinomas (serous and endometrioid) was observed. Specifically, mucinous tumors
tended to express sTn, Le(a) and sLe(a) strongly and homogeneously, whereas
serous and endometrioid tumors rarely expressed these specificities and, in
contrast, expressed Le(y) and H type 2 antigen strongly. When expressed in serous
tumors, sTn was usually distributed in a heterogeneous pattern, whereas sTn
expression in mucinous tumors was much more homogeneous. The distribution of
Le(y) in serous tumors was noticeably homogeneous. H-1, Le(x), sLe(x), Le(b), TF
and Tn specificities were rarely expressed in any type of ovarian carcinoma. Our
results provide further support for the different histogenesis of mucinous and
non-mucinous tumors and indicate alternative differentiation pathways for the 3
pathological subtypes of ovarian tumor. They also provide the basis for the
choice of carbohydrate antigens for active and passive immunotherapy of ovarian
carcinomas.
PMID- 10188719
TI - Intake of fluids and methylxanthine-containing beverages: association with colon
cancer.
AB - Although diet and its constituents have been studied extensively as risk factors
for colon cancer, much less is known about how specific types of fluid influence
colon cancer risk. In this study, we explored associations between colon cancer
and total fluids, water and methylxanthine-containing beverages such as coffee,
tea and cola; data were obtained from 1,993 incident cases of colon cancer and
2,410 population-based controls living in California, Utah and Minnesota. Our
primary objective was to determine the influence on associations of amount
consumed, confounding and effect modification. We observed few important
differences between colon cancer and fluid consumption for all subjects combined.
Among men, low levels of coffee intake were associated with an increased risk of
colon cancer relative to non-consumers of coffee (OR 1.32, 95% CI 1.02-1.67),
while at high levels of consumption, an inverse association was observed (OR
0.81, 95% CI 0.58-1.12). The observed associations were only slightly influenced
by consumption of water or other potential confounding factors, but changing the
referent group to those consuming one cup of coffee per day or less resulted in a
stronger association and a more significant inverse linear trend (OR 0.71, 95% CI
0.53-0.96). The associations with coffee and caffeine- and methylxanthine
containing beverages were strongest for proximal tumors in men. High levels of
water intake, however, were protective for distal tumors (OR for men 0.68, 95% CI
0.49-0.96). Assessment of the impact of smoking on associations between colon
cancer and coffee showed a significant interaction between smoking and coffee for
both men and women.
PMID- 10188720
TI - Analysis of T-cell-receptor beta-chain-gene usage in peripheral-blood and tumor
infiltrating lymphocytes from human non-small-cell lung carcinomas.
AB - Non-small-cell lung cancers (NSCLC) are often infiltrated by T lymphocytes. It is
postulated that the presence of tumor-infiltrating lymphocytes (TIL) reflects a
local host immune response against autologous tumors. To identify the nature of
NSCLC TIL, we have characterized the molecular structure of the TCRbeta chain
expressed by infiltrating T cells and paired PBL from 9 untreated patients (4
LLC, 3 ADC and 2 SCC). For this purpose, we have used a high-resolution PCR-based
method that determines CDR3 size patterns in TCRVbeta sub-families in fresh
tumors and their corresponding autologous PBL samples. Oligoclonality in T-cell
populations was observed in 3 (Hor, Bla and Pub) out of 9 tumor biopsies
analyzed. In contrast, the TCR repertoire of the 6 following patients as well as
of all the autologous PBL was diverse, with virtually all Vbeta specificities
expressed. Among the 3 tumors with dominant T-cell clonotypes, relative expansion
of some T-cell sub-populations was observed. One patient (Hor) with significant
TCRVbeta21 expansion in tumor compared with autologous PBL, showed over
expression of a particular TCRVbeta chain with unique Vbeta21-D-Jbeta2.7
junctional region not detected in autologous PBL. TCRVbeta21/Jbeta2.7 expansion
was also observed in IL-2-stimulated TIL cell lines and was confirmed by
sequencing analysis of the V-D-J junctional region. These results strengthen the
view that local antigen-driven selection may occur, and support the hypothesis
that anti-tumor immune response may take place in some NSCLC.
PMID- 10188721
TI - Cancer risk in mutation carriers of DNA-mismatch-repair genes.
AB - Excessive incidence of various cancers is a challenging feature of the hereditary
non-polyposis-colorectal-cancer (HNPCC) syndrome. This study estimated the cancer
incidences in HNPCC compared with the general population. Individuals in a cohort
of 1763 members of 50 genetically diagnosed families were categorized according
to their genetic status as mutation carriers, non-carriers, or individuals at 50
or 25% risk of being a carrier. Incidences of cancers in these groups were
compared with those in the Finnish population overall. In 360 mutation carriers,
standardized incidence ratios (SIR) were significantly increased for colorectal
[68; 95% confidence intervals (CI), 56 to 81], endometrial (62; 95% CI, 44 to
86), ovarian (13; 95% CI, 5.3 to 25), gastric (6.9; 95% CI, 3.6 to 12), biliary
tract (9.1; 95% CI, 1.1 to 33), uro-epithelial (7.6; 95% CI, 2.5 to 18) and
kidney (4.7; 95% CI, 1 to 14) cancers and for central-nervous-system tumours
(4.5; 95% CI, 1.2 to 12). The SIR increased with increasing likelihood of being a
mutation carrier. The cumulative cancer incidences were 82, 60, 13 and 12% for
colorectal, endometrial, gastric and ovarian cancers respectively. For other
tumours associated with increased risk, corresponding incidences were below 4%.
Interestingly, the incidence of endometrial cancer (60%) exceeded that for
colorectal cancer in women (54%). The tumour spectrum associated with germline
mutations of DNA-mismatch-repair genes involves 8 or more organ sites, suggesting
a need to develop methods to screen for extra-colonic cancer also.
PMID- 10188722
TI - Genetic pattern of prostate cancer progression.
AB - Genetic alterations in primary prostate cancer (CaP) have been extensively
studied, yet little is known about the genetic mechanisms underlying progression
of primary CaP to metastatic prostate cancer. As a result, it is not possible to
distinguish clinically indolent localized disease from potentially life
threatening tumors with high metastatic potential. To address this question, we
collected tissue from 34 autopsy-derived metastases, samples rarely analyzed in
previous studies. These were compared to a separate set of 17 prostatectomy
specimens containing 22 foci of CaP associated with 49 examples of high-grade
prostatic intraepithelial neoplasia (PIN), a histological precursor of CaP. We
compared the loss of heterozygosity (LOH) profiles of high-grade PIN, primary CaP
and metastases by analyzing 33 microsatellite markers previously found to have
high frequencies of LOH in primary CaP. These markers were on chromosomes 5q, 6q,
7q, 8p, 9p, 10q, 11p, 13q, 16q, 17, 18q and 21q. In addition, markers on
chromosomes 4p, 11q, 14q and 20q with no reported LOH in primary CaP were
analyzed to determine the frequency of background LOH. In PIN lesions, the rate
of LOH was significant only at D5S806 (20%) and D16S422 (29%). In addition,
different PIN lesions within the same prostate gland were genetically diverse,
indicating divergent evolution of synchronous neoplastic precursor lesions. LOH
frequency was progressively higher in primary CaP and metastatic lesions. In
primary CaP, significant losses occurred at the 8p, 10q, 11p, 16q, 17p, 18q and
21q loci (range 17-43%). Distinct patterns of LOH frequencies were observed in
primary CaP compared with metastases. Although some loci (D16S422, D17S960,
D21S156) showed similar frequencies of LOH in primary CaP and metastatic CaP,
most other loci showed up to 7-fold metastasis-related increases. The metastatic
samples revealed previously unrecognized prostate cancer LOH at D5S806, D6S262,
D9S157, D13S133 and D13S227. These significant stage-specific differences in LOH
frequency specify genetic loci that may play key roles in CaP progression and
could represent clinically useful biomarkers for CaP aggressiveness.
PMID- 10188723
TI - An interlaboratory study to determine the presence of human papillomavirus DNA in
esophageal carcinoma from China.
AB - Esophageal-carcinoma samples originating from the high-incidence area of China
were tested in 2 different laboratories, each using a different degenerate PCR
approach. Results confirmed the notion that none of the PCR approaches available
for HPV-DNA detection today, is optimal for detecting all known HPV types at
equal sensitivity and specificity. In combining results obtained in both
laboratories, HPV DNA was demonstrated in 20/117 (17.1%) esophageal-carcinoma
samples analyzed. HPV DNA was detected in 3/70 (4.3%) diagnostic biopsies, 7/23
(30.4%) surgical specimen and 10/24 (41.6%) cytological scrapings originating
from the entire surface of the esophagus. Mucosotropic HPV types were present in
7/117 (6%) samples, only 3 being of the high-risk types (HPV 16, 18, 33). Other
mucosal types found were HPV 6, 11, 13, 53 and 54. Cutaneous HPV types were
present in 14/117 (12.0%) samples. HPVs 20 and 38 were present in 3 (2.6%) of the
total samples and, in each case, together with another HPV type within one
lesion. Two putative new HPV types, DL347 and DL 369, were identified.
PMID- 10188724
TI - Mitogenic autoantibodies in Helicobacter pylori-associated stomach
cancerogenesis.
AB - Colonization of the bacterium Helicobacter pylori of gastric mucosa plays an
important role in stomach carcinogenesis, while the gastric mucosa and nearby
lymphoid tissue are active sites of humoral immunity against both bacteria and
tumor. In a broad study on the humoral immunity of stomach-cancer patients (5
patients with diffuse- and intestinal-type stomach carcinoma), we immortalized
spleen cells by using human hybridoma technology and isolated 11 hybrid clones (9
IgM, 1 IgG and 1 IgA) which react with defined proteins on different stomach
cancer cells and, interestingly, also with distinct proteins on H. pylori; 4 of
these antibodies are mitogenic and stimulate the proliferation of stomach-cancer
cells in vitro. Furthermore, immunohistochemical studies define these 4 clearly
as autoantibodies, in view of their reactivity to normal epithelial cells.
Sequence analysis of the genes for the immunoglobulin heavy (V(H)) and light
(V(L)) chain variable regions revealed that most of the human antibodies belong
to the V(H)3, Vlambda I and III gene families (DP-49, DPL-5 and DPL-23) and are
germ-line configured.
PMID- 10188725
TI - Differential regulation of IL-6 promoter activity in a human ovarian-tumor cell
line transfected with various p53 mutants: involvement of AP-1.
AB - In human ovarian carcinomas, the p53 tumor-suppressor gene is frequently mutated.
Interleukin-6 (IL-6) in these tumors is known to stimulate tumor-cell
proliferation. In order to evaluate the effect of several p53 phenotypes on the
IL-6 promoter activity, the human ovarian wild-type (wt)-p53 cell line A2780 was
stably transfected with an empty plasmid (CMV) or (m)-175-, m-248- or m-273-p53.
Electrophoretic mobility-shift assays revealed differences in activator protein-1
(AP-1) DNA-binding activity in the various clones. The CMV and m-273 clone had
comparable amounts of AP-1. The m-175 clone displayed the least and m-248 the
most pronounced AP-1 binding. Supershift analysis of AP-1/DNA complexes with
antibodies against the AP-1 sub-units, c-Fos, FosB, Fra-1, Fra-2, c-Jun, JunB,
and JunD, revealed that the AP-1/DNA complexes in the various clones had
different compositions. Fra proteins were basically present only in m-175 and m
248 AP-1. IL-6-promoter activity was evaluated in the presence and absence of the
AP-1 binding site which showed that the m-175-transfected clone has a
transcriptional suppressing AP-1, whereas the CMV and the m-273 clones have an
activating AP-1. Exposure of the p53 clones to tumor-necrosis factor-alpha (TNF
alpha) clearly altered the AP-1/DNA complex composition. IL-6-promoter activity
was enhanced by TNF-alpha irrespective of the presence of an AP-1 binding site,
while the degree of activation differed in the various clones, being most
pronounced in the m-175 and m-248 clones. The results demonstrate that the basic
and activated IL-6-promoter activity is differently regulated in the various p53
clones, possibly due to alterations in the AP-1 composition.
PMID- 10188726
TI - Differential expression of the hepatic transcript of beta-galactoside alpha2,6
sialyltransferase in human colon cancer cell lines.
AB - The activity of beta-galactoside alpha2,6-sialyltransferase (ST6Gal.1), the
enzyme responsible for the addition of sialic acid in alpha2,6-linkage to N
acetyllactosaminic (Gal beta1,4GlcNAc) units of glycoconjugates, is increased in
the vast majority of colon cancer specimens, and a positive correlation with an
invasive phenotype has been suggested by several studies. In many tissues,
ST6Gal.1 is regulated mainly at the transcriptional level through the use of
different cell-specific promoters which generate transcripts differing in their
5'-untranslated regions. With the aim of understanding the molecular bases of the
increased ST6Gal.1 expression in colon cancer, we investigated the expression of
mRNA species in colon cancer cell lines and the relationship with enzyme activity
and extent of alpha2,6-sialylation of cell glycoproteins. All cell lines examined
express the form containing the 5'-untranslated exons Y and Z, typical of the
"basal" expression of the gene, while others express also the liver transcript.
This indicates that colon cancer cell lines can be grouped according to
expression of the liver transcript of ST6Gal.1. The cell lines expressing only
the Y+Z form display, in general, a lower activity:mRNA ratio, which might
indicate reduced translational efficiency. The level of alpha2,6-sialylation of
cell glycoproteins, as determined by reactivity with the Sambucus nigra lectin,
is closely associated with the level of enzyme activity.
PMID- 10188727
TI - A comparison of an anti-gastrin antibody and cytotoxic drugs in the therapy of
human gastric ascites in SCID mice.
AB - The therapeutic effect of antibodies raised by the immunogen Gastrimmune was
compared with both a CCKB/gastrin receptor antagonist, CI-988, and 5
Fluorouracil/leucovorin in a gastric cancer model. The human gastric ascites cell
line, MGLVA1asc, produced and secreted progastrin and glycine-extended gastrin as
determined by radioimmunoassay and immunocytochemistry. Cells were also stained
with an antiserum directed against the human CCKB/gastrin receptor. MGLVAI asc
cells were injected i.p. into SCID mice. Antibodies raised by Gastrimmune
immunization of rabbits (affinity for G17 of 0.15 nM and GlyG17 of 0.47 nM) were
passively infused i.p. and significantly enhanced survival by up to 5 days
(p=0.0024 from vehicle controls). The enhancement in survival was not
significantly different from that achieved by treatment with 5-Fluorouracil and
leucovorin. A CCKB/gastrin receptor antagonist, CI-988, did not affect survival
with cells injected at 7.5 x 10(5) cells/mouse but significantly increased the
survival of mice injected with a lower cell innoculum of 5 x 10(5) cells/mouse
from 30 to 35 days (p=0.0186). At this lower innoculum antibodies raised by
Gastrimmune induced complete survival in 2 animals with the remaining dead by day
36 (p=0.0022). Thus, both endocrine and autocrine pathways mediated by precursor
and mature gastrin molecules may be jointly operational in the gastric cancer
scenario and may be important targets for therapeutic agents.
PMID- 10188728
TI - Role of protein kinase C isoforms in locomotion of Walker 256 carcinosarcoma
cells.
AB - Treatment with low (nanomolar) concentrations of phorbol-12-myristate-13-acetate
(PMA) for 5 to 30 min suppresses locomotion of Walker 256 carcinosarcoma cells,
suggesting that activation of protein kinase C (PKC) is a stop signal for tumor
cell locomotion. We have compared the effects of PMA on cell shape and motility
with down-regulation of specific PKC isoforms. Using specific antibodies, we show
that Walker carcinosarcoma cells express PKC isoforms alpha, betaI, betaII,
gamma, lambda, mu, eta and zeta. Short-term incubation with PMA induced a marked
shift of isoforms alpha, betaI, betaII, gamma and eta to the particulate
fraction. Long-term incubation with PMA (0.1 microM, 6 hr) resulted in
significant reduction of expression of conventional PKCs alpha, betaI, betaII and
gamma and of the novel PKC eta to 10% to 26% of controls. Down-regulation of PKC
alpha, betaI and betaII by long-term incubation with PMA was reversible after
removal of PMA, whereas that of isoforms gamma and eta was not. The motile
properties of cells after down-regulation of PKC isoforms were investigated.
Concomitant with down-regulation of PKC isoforms, long-term incubation of cells
with PMA resulted in recovery of the polar shape and the ability to migrate.
Motility and polarized shape of the down-regulated cells were no longer
susceptible to short-term treatment with PMA, showing that active PKC is indeed
responsible for the inhibitory effects of PMA. Effects of long-term incubation
with PMA on cell shape and motility were reversible. Our findings strongly
suggest that PKCs alpha, betaI and betaII activated by PMA are involved in
stopping Walker carcinosarcoma cell locomotion.
PMID- 10188729
TI - N-(4-hydroxyphenyl) retinamide is cytotoxic to melanoma cells in vitro through
induction of programmed cell death.
AB - Melanoma is a highly malignant and increasingly common tumour. Since metastatic
melanoma remains incurable, new treatment approaches are needed. Previously, we
reported that the synthetic retinoid N-(4-hydroxyphenyl)retinamide (fenretinide,
HPR) induces apoptosis in neuroblastoma cells, sharing a neuroectodermal origin
with melanoma cells. Since no data exist thus far on the effects of HPR on human
melanoma tumours, our purpose was to investigate the in vitro modulation of cell
growth and apoptosis by HPR in melanoma cells. Ten human melanoma cell lines were
exposed in vitro to increasing concentrations of HPR. Dose-dependent growth
inhibition and cytotoxicity were observed. According to cytofluorimetric
analysis, propidium iodide staining and TUNEL assay, HPR-treated melanoma cells
were shown to undergo apoptosis. However, IC50 values ranged from 5 to 28 microM,
while IC90 values were between 10 and 45 microM. These last concentrations are
approximately 10-fold higher than those achievable in patients given oral HPR. To
explore the potential of new delivery strategies, HPR was loaded at high
concentrations into immunoliposomes directed to disialoganglioside GD2, a tumour
specific antigen extensively expressed by neuroectoderma-derived tumours.
Treatment of melanoma cells for a short time (2 hr) with HPR-containing
immunoliposomes followed by culture in drug-free medium gave rise to apoptosis of
target cells, whereas cells treated for 2 hr with equivalent concentrations of
the free drug survived. The efficacy of immunoliposomal HPR was strongly
dependent on the density of GD2 expression in the different cell lines.
PMID- 10188730
TI - GD2-mediated melanoma cell targeting and cytotoxicity of liposome-entrapped
fenretinide.
AB - Melanoma is a highly malignant and increasingly common neoplasm. Because
metastatic melanoma remains incurable, new treatment approaches are needed.
Immunoliposomes have been previously shown to enhance the selective localization
of immunoliposome-entrapped drugs to solid tumors with improvements in the
therapeutic index of the drugs. Previously, we reported that the synthetic
retinoid fenretinide (HPR) is an inducer of apoptosis in neuroblastoma (NB)
cells, sharing the neuroectodermal origin with melanoma cells. HPR is a strong
inducer of apoptosis also in melanoma cells, although at doses 10-fold higher
than those achievable clinically. Thus, our purpose was to investigate the in
vitro potentiation of its cytotoxic effect on melanoma cells in combination with
long-circulating GD2-targeted immunoliposomes. GD2 is a disialoganglioside
extensively expressed on tumors of neuroectodermal origin, including melanoma.
Murine anti-GD2 antibody (Ab) 14.G2a and its human/mouse chimeric variant ch14.18
have been ligated to sterically stabilized liposomes by covalent coupling of Ab
to the polyethylene glycol (PEG) terminus. Ab-bearing liposomes showed specific,
competitive binding to and uptake by various melanoma cell lines compared with
liposomes bearing non-specific isotype-matched Abs or Ab-free liposomes.
Cytotoxicity was evaluated after 2 hr treatment, followed by extensive washing
and 72 hr incubation. This treatment protocol was designed to minimize non
specific adsorption of liposomes to the cells, while allowing for maximum Ab
mediated binding. When melanoma cells were incubated with 30 microM HPR entrapped
in anti-GD2 liposomes, a significant reduction in cellular growth was observed
compared to free HPR, entrapped HPR in Ab-free liposomes or empty liposomes.
Cytotoxicity was not evident in tumor cell lines of other origins that did not
express GD2. Growth of NB cells was also inhibited by immunoliposomes with
entrapped HPR.
PMID- 10188731
TI - EB/RP gene family encodes tubulin binding proteins.
AB - Mutations in the adenomatous polyposis coli (APC) gene are linked to the
dysplastic transformation of colorectal polyps and represent an early step in the
development of colorectal tumors. Ninety-four percent of all mutations result in
the expression of a truncated APC protein lacking the C-terminal region. The C
terminal region of the APC protein may have a tumor suppressor function as its
absence appears to be linked to the development of dysplastic lesions. Recently,
we discovered and characterized a protein called RP1 which binds specifically to
the C-terminal region of the APC protein. We show now that RP1 and the other
known members of the EB/RP family (EB1 and RP3) also bind directly to tubulin,
both in vitro and in vivo. Immunohistochemical analyses reveal a distinct
staining pattern during interphase as well as an association of RP1/EB1 with
mitotic microtubule structures. The previously described puncta of the APC
protein at the leading edge of membrane protrusions contact microtubule fibers
that contain RP1 or EB1.
PMID- 10188732
TI - Tumor targeting with newly designed biparatopic antibodies directed against two
different epitopes of the carcinoembryonic antigen (CEA).
AB - In an attempt to improve tumor targeting and tumor retention time of monoclonal
antibodies (MAbs), we prepared biparatopic antibodies (BpAbs) having the
capability of binding 2 different non-overlapping epitopes on the same target
antigen molecule, namely, the carcinoembryonic antigen (CEA). Six BpAbs were
constructed by coupling 2 different Fab' fragments from 4 different specific anti
CEA MAbs recognizing 4 CEA epitopes (Gold 1-4). Demonstration of the double
paratopic binding of these antibodies for CEA was confirmed in vitro by
inhibition radioimmunoassay and cross-inhibition analysis by surface plasmon
resonance (SPR; BIACORE) technology. Using the latter technique, the affinity
constants for CEA immobilized onto the sensor chip were found to range from 0.37
to 1.54 x 10(9) M(-1) for the 4 parental F(ab')2 fragments and from 1.88 to 10.14
x 10(9) M(-1) for the BpAbs, demonstrating the advantage of biparatopic binding
over conventional F(ab')2 binding. The Ka improvement was particularly high for
BpAb F6/35A7 and BpAb F6/B17 with a 9.5- and 8.1-fold increase, respectively, as
compared with the parental F(ab')2. In vivo, the 6 BpAbs were compared with their
2 respective parental F(ab')2 by injection of 131I-BpAb/125I-F(ab')2 parental
fragments into nude mice xenografted with the human colon carcinoma T380.
Dissection 72 hr post-injection demonstrated that BpAb B17/CE25 and BpAb F6/B17
gave higher tumor uptake than that of their parental F(ab')2. This finding is
particularly interesting for BpAb F6/B17, which compared favorably with the F6
F(ab')2, one of the best parental F(ab')2 fragments used in our study.
PMID- 10188733
TI - Expression of MDM2 during mammary tumorigenesis.
AB - The MDM2 oncoprotein encodes a 90 kDa nuclear phosphoprotein capable of
abrogating the growth suppressive functions of p53 and pRb tumor suppressor
proteins by direct interaction. Alternative splicing of MDM2 protein coding
sequences has been documented during tumor progression in human ovarian and
bladder carcinomas. The aim of this study was to determine whether alternative
splicing of MDM2 occurs during breast tumorigenesis in mice and humans and
whether protein coding sequences were affected. Specimens representing normal and
malignant breast tissues from the murine D2 mammary tumor model system and human
breast carcinomas were examined. Three distinct mdm2 mRNA transcripts of 3.3, 1.6
and 1.5 kb were detected in normal and malignant murine mammary tissues by
Northern blot analysis using a full-length mdm2 cDNA probe. Additional Northern
blot analysis using a probe derived from exon 12 of murine mdm2 demonstrated that
the 1.5 and 1.6 kb transcripts lack sequences encoding the C-terminus of the
protein. No evidence of internal deletions of protein coding sequences of mdm2
was detected in any of the normal mammary tissues or D2 murine mammary tumors
examined by reverse transcription PCR (RT-PCR). Three distinct MDM2 transcripts
of 6.7, 4.7 and 1.9 kb were detected in malignant human breast tissue by Northern
blot analysis using a cDNA probe specific for the complete open reading frame of
human MDM2. However, a cDNA probe specific for the last exon of human MDM2
hybridized only to the 6.7 and 4.7 kb transcripts, demonstrating that the 1.9 kb
transcript lacked protein coding sequences contained in exon 12. Similarly, no
internal deletions were detected in a panel of malignant human breast tissues
using RT-PCR and analogous primers within human MDM2. Therefore, breast tumors
differ from other solid tumors reported previously in that no internal deletions
of MDM2 protein coding sequences were observed. However, the data document the
presence of multiple MDM2 mRNA transcripts in both normal and malignant breast
tissues. A subset of MDM2 transcripts were shown to lack the last exon which
contains sequences coding for the RING and zinc fingers and domains which are
targets for caspase-3 mediated proteolytic degradation and are required to target
p53 for proteosomal degradation.
PMID- 10188734
TI - Insulin receptor substrate 1 is a target for the pure antiestrogen ICI 182,780 in
breast cancer cells.
AB - The pure antiestrogen ICI 182,780 inhibits insulin-like growth factor (IGF)
dependent proliferation in hormone-responsive breast cancer cells. However, the
interactions of ICI 182,780 with IGF-I receptor (IGF-IR) intracellular signaling
have not been characterized. Here, we studied the effects of ICI 182,780 on IGF
IR signal transduction in MCF-7 breast cancer cells and in MCF-7-derived clones
overexpressing either the IGF-IR or its 2 major substrates, insulin receptor
substrate 1 (IRS-1) or src/collagen homology proteins (SHC). ICI 182,780 blocked
the basal and IGF-I-induced growth in all studied cells in a dose-dependent
manner; however, the clones with the greatest IRS-1 overexpression were clearly
least sensitive to the drug. Pursuing ICI 182,780 interaction with IRS-1, we
found that the antiestrogen reduced IRS-1 expression and tyrosine phosphorylation
in several cell lines in the presence or absence of IGF-I. Moreover, in IRS-1
overexpressing cells, ICI 182,780 decreased IRS-1/p85 and IRS-1/GRB2 binding. The
effects of ICI 182,780 on IGF-IR protein expression were not significant;
however, the drug suppressed IGF-I-induced (but not basal) IGF-IR tyrosine
phosphorylation. The expression and tyrosine phosphorylation of SHC as well as
SHC/GRB binding were not influenced by ICI 182,780. In summary, downregulation of
IRS-1 may represent one of the mechanisms by which ICI 182,780 inhibits the
growth of breast cancer cells. Thus, overexpression of IRS-1 in breast tumors
could contribute to the development of antiestrogen resistance.
PMID- 10188735
TI - Establishment of a human hemangiosarcoma cell line (ISO-HAS).
AB - A cell line (ISO-HAS) has been established from tumor tissue of a human
hemangiosarcoma arising on the scalp by the use of conditioned medium from a
murine-phenotypic angiosarcoma cell line (ISOS-1). Cells have been cultured for
more than 2 years with up to 100 passages. The cells retained endothelial-cell
properties, such as a characteristic cobblestone appearance at confluency,
contact-inhibited growth, active uptake of acetylated low-density lipoprotein
labeled with 1,1-dioctadecyl 1,3,3,3,3-tetramethyl-indocarbocyanine perchlorate
(DiI-Ac-LDL) and CD31 expression. However, they were weakly positive for von
Willebrand-factor (vWf) antigen and for binding of Ulex europaeus agglutinin-I
(UEA-I) lectin, and lacked tube-formation activity. These findings indicate that
ISO-HAS is a poorly differentiated endothelial cell line. ISO-HAS cells showed
accumulation of p53 protein in the nuclei, and a new-typed p53-gene point
mutation was found in exon 7 at codon 240. When inoculated s.c. into severe
combined-immunodeficiency (SCID) mice, the cells showed solid-tumor growth that
caused death. These properties suggest that ISO-HAS is a malignant endothelial
cell line with high tumorigenicity.
PMID- 10188736
TI - Time-related effects of estrogen withdrawal on proliferation- and cell death
related events in MCF-7 xenografts.
AB - Endocrine treatments for human breast cancer have been based largely upon the
removal of estrogenic stimuli. The regression of tumors after estrogen
deprivation has generally been characterized as being due to reduced
proliferation but more recently has been recognized to also involve increased
apoptosis. The aim of our experiments was to define the associated changes in
certain proliferation- and cell death-related biological parameters after hormone
withdrawal from estrogen-dependent MCF-7 xenografts in athymic nude mice using
immunohistochemical techniques. The baseline estrogen receptor (ER) level of this
MCF-7 xenograft was relatively low (average H score 23) but it was strongly Bcl-2
, PgR- and pS2-positive, indicating the functional integrity of estrogen
signaling. Changes in proliferation (Ki-67), apoptosis, ER, progesterone receptor
(PgR), cyclin D1, p27kip1, Bcl-2 and Bax expression were assessed during the 2
weeks after estrogen deprivation. ER levels rose markedly after estrogen
ablation, whereas PgR levels fell to about 10% of baseline and pS2 levels halved.
The proportion of Ki-67-positive cells was unchanged after 24 hr but by day 14
had reduced by about 80%. The normal levels of cyclin D1 also reduced after
estrogen withdrawal in contrast to the rapid increase in levels of cyclin
dependent kinase inhibitor p27kip1. This latter increase appeared to occur in
advance of the changes in Ki-67. The proportion of apoptotic cells increased from
a mean 1.5% at baseline to 2.9% after 3 days and 4.7% after 14 days. There were
reductions in both Bcl-2 and Bax staining but these appeared to be greater for
Bcl-2, effectively decreasing the Bcl-2/Bax ratio. Our results provide a
framework for the use of these parameters as intermediate markers in comparisons
of hormonal agents for human breast cancer treatment.
PMID- 10188737
TI - Lack of correlation between ventricular late potentials and left ventricular mass
in top-level male athletes.
AB - PURPOSE: The aim of this study was to establish: 1) the prevalence of abnormal
signal-averaged electrocardiogram (SAECG) in a large population of top-level
athletes and 2) the relationship between SAECG parameters and left ventricular
mass. One-hundred and fifty-three elite male athletes without apparent heart
disease, symptoms, or arrhythmias were studied. METHODS: Fifty-six athletes (37%)
had increased left ventricular mass (> 134 g.m(-2)). All athletes underwent time
domain SAECG on 300-400 heart beats recorded at rest from three bipolar
orthogonal tests with a filter setting of 40-250 Hz. Criteria for abnormality
were 1) filtered QRS duration > 114 ms, 2) duration of low-amplitude signals > 38
ms, or 3) root mean square voltage of the last 40 ms of the filtered QRS < 20
microV. RESULTS: The prevalence of abnormal SAECG was 7.2% (abnormality of one
parameter), 6.5% (abnormality of two parameters), and 5.8%(abnormality of three
parameters). The prevalence of abnormal SAECG was similar in athletes with or
without increased left ventricular mass. CONCLUSIONS: In conclusion, this study
showed: 1) the low rate of positive results of SAECG parameters in top-level male
athletes, similar to that found in healthy sedentary subjects; and 2) the lack of
correlation between left ventricular mass and overall SAECG parameters.
PMID- 10188738
TI - Regulation of MAC-1 (CD11b/CD18) expression on circulating granulocytes in
endurance runners.
AB - PURPOSE: We tested the hypothesis that degranulation of granulocytes and
upregulation of the granulocyte integrin MA-1 (CD11b/CD18) are related to
exercise duration and/or intensity. We also investigated whether or not the
expression of MAC-1 would be influenced by body temperature or dehydration.
Moreover, we tested the hypothesis that changes in leukocyte counts and changes
in MAC1 expression with endurance exercise are independently regulated. METHODS:
In eight amateur runners, MAC-1 (CD11b/CD18) surface expression on granulocytes
was determined by fluorescent antibody cell sorting, before and after an
incremental maximal treadmill test, a moderate 3-h run, and a competitive
marathon race. RESULTS: Expression CD11b on granulocytes was increased by 10+/
9.6% (P < 0.05) after the maximal treadmill test and by 84+/-76% (P < 0.01) after
the marathon run. There was no change in CD11b expression after the moderate 3-h
run. CD18 expression was not significantly changed after any of the exercise
protocols. CONCLUSION: Expression of CD11b on granulocytes is increased with
intense endurance exercise, either incremental maximal treadmill testing or
competitive marathon running, but not in moderate endurance training. Thus,
exhaustive exercise may be one mechanism for the upregulation of integrin
adhesive receptors on granulocytes. This phenomenon could be in part responsible
for increased adhesion of granulocytes to endothelial cells and could facilitate
tissue infiltration after endurance exercise.
PMID- 10188739
TI - The benefits of wearing a compression sleeve after ACL reconstruction.
AB - PURPOSE: It was the purpose of the present study to examine the possibility of
increased muscle coordination after anterior cruciate ligament (ACL)
reconstruction through the wearing of a compression sleeve. METHODS: Thirty-six
patients were studied who had undergone unilateral ACL reconstruction at least 12
months previously. All subjects were required to perform a 10-cm standing drop
jump from an elevated platform onto a force plate, to land on one leg, and
thereafter maintain a one-legged balance for 25 s. This task was repeated three
times without and three times with an elastic compression sleeve worn on the
reconstructed limb. For analysis, the task was partitioned into a landing phase
(150 ms), an adjusting phase (10s), and a balancing phase (10s). The peak impact
loadings were measured in each direction (Fx, Fy, and Fz) during landing, while
force-time integrals (intFz, intFy, and intFz) and root mean square (RMS) error
of these forces were calculated for the adjusting and balancing phases. The path
length and RMS of the center of pressure coordinates (Ax and Ay) were obtained
for the adjusting and balancing phases combined. RESULTS: Drop landings with the
bandage produced significantly larger (P < 0.001) peak ground reaction forces in
the vertical and anteroposterior direction, suggesting increased subject
confidence in their knee. Wearing the knee bandage also enabled the patients to
reduce all measured parameters in the anteroposterior direction (rmsFx, intFx,
rmsAx) during both the adjusting and balancing phases (P < 0.001 ). A significant
reduction in the center of pressure path length further indicated an enhanced
steadiness during the one-legged stance. CONCLUSIONS: It was concluded that a
compression sleeve improved the total integration of the balance control system
and muscle coordination.
PMID- 10188740
TI - Hematocrits of triathletes: is monitoring useful?
AB - PURPOSE: The purpose of this manuscript was to provide a basis for establishing
safety cutoffs for hematocrit levels in triathletes and background data for
possible future medical control regulations. METHODS: Competitors from three
different distance triathlons participated: Olympic (N = 118), half-Ironman (N =
87), and Ironman (N = 207). Blood samples were drawn within 24-36 h prerace (N =
412) and within minutes of race finish (N = 296). Prerace hematocrits
approximated a normal distribution for men (X = 43.2 +/- 2.9) and women (X =
40.2+/-2.6). Prerace hematocrits decreased as competitive distance increased for
men (X = 45.0, 43.4, 42.5; respectively; P < 0.01) but not for women (P > 0.05).
RESULTS: Mean race day changes were small but statistically significant for
Olympic and Ironman men and for half-Ironman women. Individual responses were
more variable with hemoconcentration occurring in 57%, hemodilution in 43%, and
no change in 2% of participants. The magnitude of individual responses was also
variable with hematocrit changes ranging from -7.1 to + 10%. No athlete in this
sample had a hematocrit that would place him/her in the "danger zone" (Hct >
55%). CONCLUSIONS: Cutoff values (3 SD above the means) of 52% for men and 48%
for women are suggested by these data. However, the relationship of these cutoffs
to either athlete safety or the ability to detect rules violations remains
unknown.
PMID- 10188741
TI - Effects of exercise combined with diet therapy on protein utilization in obese
children.
AB - PURPOSE: Hypocaloric therapy may adversely affect protein utilization in obese
children given that metabolic reactions involving protein, a nutrient essential
for growth, are energy-dependent. Because physical activity influences nutrient
utilization and may modulate the effects of reduced energy intake, exercise
combined with diet therapy may be beneficial with regard to protein metabolism.
The primary purpose of this study was to evaluate changes in protein utilization
in response to sequential addition of an exercise program to dietary intervention
in obese children. METHODS: After a 2-wk baseline period, five subjects aged 8-10
yr reduced energy intake [-2092 to -2510 kJ.d(-1)(-500 to -600 kcal.d(-1))] for
12 wk. A walking program [5 d.wk(-1), 3.2-4.8 km.d(-1) (2-3 miles.d(-1))] was
implemented during the final 6 wk of diet therapy. At baseline and after phases I
(diet only) and II (exercise and diet) of intervention, 15N-glycine was used to
assess protein synthesis (PS), protein breakdown (PB), net turnover (NET = PS -
PB), and nitrogen flux (Q). RESULTS: Subjects lost 4.2+/-0.4 kg during the 12-wk
intervention period (P < or = 0.05). With diet only, NET decreased (P < or =
0.05) due to a reduction in PS (P < or = 0.05) accompanied by no change in PB.
Although PS increased with walking (P < or = 0.05), NET did not return to
baseline levels due to a concurrent increase in PB (P < or = 0.05). Changes in PS
and PB yielded an increase in Q (P < or = 0.05), a measure of amino acid cycling
between protein and free amino acid pools. CONCLUSIONS: These results suggest
that exercise offers metabolic benefits for obese children during diet-induced
weight loss. Longitudinal studies are needed to assess long-term health outcomes
associated with the observed changes in protein utilization.
PMID- 10188742
TI - Fluid ingestion does not influence intense 1-h exercise performance in a mild
environment.
AB - PURPOSE: It is generally recommended that fluid be ingested during exercise at a
rate that prevents body mass loss and prevents dehydration. It is, however, not
known whether these recommendations are valid during intense endurance exercise
in a mild environment. The purpose of this study was to examine the effect of
fluid ingestion volume on heart rate (HR), rectal temperature, plasma
electrolytes, and performance during intense endurance exercise at 21 degrees C.
METHODS: Eight well-trained men (26+/-1 yr; 79.6+/-3.5 kg; VO2peak = 5.05+/-0.17
L.min(-1) ; mean+/-SEM) cycled for 45 min at 80+/-1% VO2peak while receiving
either no fluid replacement (NF), a volume of water that prevented body mass loss
(FR-100 = 1.47+/-0.05 L), or 50% of this volume (FR-50 = 0.72+/-0.03 L). The 45
min exercise bout was followed immediately by a 15-min "all-out" performance
ride. RESULTS: NF was associated with a 1.9+/-0.0% body mass loss, while FR-50
and FR-100 resulted in losses of 1.0 = 0.1% and 0.0+/-0.1%, respectively.
Although values tended to be higher in NF, fluid ingestion had no significant
effect on HR or rectal temperature during exercise. Reductions in plasma volume
and increases in plasma sodium and potassium concentrations during exercise were
largely unaffected by fluid ingestion. RPE increased to a similar extent during
exercise in the three trials while a mild increase in the degree of stomach
bloating/fullness was evident in FR-100. Work completed during the 15-min
performance ride was similar in the three trials (NF: 273+/-8, FR-50: 267+/-8, FR
100: 269+/-9 kJ). CONCLUSIONS: There appears to be little benefit from ingesting
water during intense 1-h cycling exercise in mild environmental conditions since
such ingestion has no significant effect on HR, body temperature, plasma volume,
plasma electrolytes, or performance.
PMID- 10188743
TI - Influence of high and low glycemic index meals on endurance running capacity.
AB - PURPOSE: The purpose of this study was to examine the effect of high and low
glycemic index (GI) carbohydrate (CHO) pre-exercise meals on endurance running
capacity. METHODS: Eight active subjects (five male and three female) ran on a
treadmill at approximately 70% VO2max to exhaustion on two occasions separated by
7 d. Three hours before the run after an overnight fast, each subject was given
in a single-blind, random order, isoenergetic meal of 850+/-21 kcal (mean+/-SEM;
67% carbohydrate, 30% protein, and 3% fat) containing either high (HGI) or low
(LGI) GI carbohydrate foods providing 2.0 g CHO.kg(-1) body weight. RESULTS:
Ingestion of the HGI meal resulted in a 580% and 330% greater incremental area
under the 3-h blood glucose and serum insulin response curves, respectively.
Performance times were not different between the HGI and LGI trials (113+/-4 min
and 111+/-5 min, respectively). During the first 80 min of exercise in the LGI
trial, CHO oxidation was 12% lower and fat oxidation was 118% higher than in the
HGI trial. Although serum insulin concentrations did not differ between trials,
blood glucose at 20 min into exercise in the HGI trial was lower than that during
the LGI trial at the same time (3.6+/-0.3 mmol.L(-1) vs 4.3+/-0.3 mmol.L(-1); P <
0.05). During exercise, plasma glycerol and serum free fatty acid concentrations
were lower in the HGI trial than in the LGI trial. CONCLUSIONS: This results
demonstrate that although there is a relative shift in substrate utilization from
CHO to fat when a low GI meal is ingested before exercise compared with that for
a high GI meal, there is no difference in endurance running capacity.
PMID- 10188745
TI - Effect of exercise during the follicular and luteal phases on indices of
oxidative stress in healthy women.
AB - PURPOSE: Eleven healthy nonsmoking women (24+/-1.1 yr) exercised for 30 min at 75
80% VO2max during the follicular (F) and luteal (L) phases of their menstrual
cycle to determine whether menstrual phase influenced indices of oxidative
stress. METHODS: Subjects completed the exercise in a randomized order. Subjects
reported between 0800 and 0900 in a postabsorptive state, rested for 15-30 min,
and had a venous blood sample obtained by Vacutainer before and after exercise.
RESULTS: Resting estradiol was 54.4+/-12.0 pg.mL(-1) for F phase and was
significantly higher in L phase (147.2+/-25.5 pg.mL(-1)). Plasma malondialdehyde
and thiobarbituric acid substances were no different before and after exercise
independent of menstrual cycle phase. No differences in resting blood total
glutathione (TGSH), oxidized glutathione (GSSG), and reduced glutathione (GSH)
were evident comparing the F and L phases. After exercise, TGSH decreased (P =
0.03) but reached significance only in the F phase = 8.1 %(P = 0.04), L phase =
2.5% (P = 0. 15). Exercise increased GSSG 10.5% in F (P = 0.15) and 27.8% in L
phases(P = 0.01). GSH decreased after exercise independent of menstrual phase (F
= 17%, L = 16%, P = 0.01). CONCLUSION: These data suggest that 30 min of moderate
intensity exercise in female subjects can result in mild oxidative stress as
indicated by blood glutathione status and that menstrual cycle phase has minimal
influences on these exercise responses.
PMID- 10188744
TI - Effect of vitamin B-6 supplementation on fuels, catecholamines, and amino acids
during exercise in men.
AB - PURPOSE: In two separate but identical studies, the effect of vitamin B-6
supplementation was examined on plasma energy substrates, catecholamines, and 13
amino acid concentrations during exercise. METHODS: Eleven trained men performed
two separate exhaustive exercise tests at 71.0+/-4.6% VO2max during two separate
9-d controlled diet periods. Exercise test 1 (T1C) occurred following a control
diet, and test 2 (T2B6) occurred following a vitamin B-6 supplemented diet (20 mg
PN.d(-1)). Blood was drawn pre, during (60 min), post, and post-60 min of
exercise, and plasma was analyzed for glucose, lactate, glycerol, free fatty
acids (FFA), catecholamines (N = 5), and amino acids (N = 5). RESULTS: Mean FFA
concentrations changed over time in both tests (P < 0.001) and were lower in T2B6
compared to T1C at pre (P = 0.03), during (P = 0.05), and post-60 min (P = 0.04)
of exercise. Mean lactate, glycerol, and catecholamine concentrations only
changed over time (P < 0.0001). The only significant changes in amino acid
concentrations were for lower tyrosine (P = 0.007) and methionine (P = 0.03)
concentrations in T2B6 relative to TIC at post-60 min of exercise and
postexercise, respectively. No differences were observed in exercise times to
exhaustion between TIC (108+32.6 min) and T2B6 (109+51.2 min). CONCLUSIONS: These
results indicate that vitamin B-6 supplementation can alter plasma FFA and amino
acid concentrations during exhaustive endurance exercise without affecting
endurance.
PMID- 10188746
TI - Effects of dietary protein on enzyme activity following exercise-induced muscle
injury.
AB - PURPOSE: The objective of this investigation was to determine the effects of
varying levels of dietary protein on the postexercise increase in serum and
muscle enzyme activity normally observed following exercise-induced muscle
injury. METHODS: Serum creatine kinase (CK), serum aspartate aminotransferase
(AST), and muscle glucose-6-phosphate dehydrogenase (G-6-PD) activities were
measured in rats fed for 10 d on high (50%), normal (12%), or low (4%) protein
diets following a single bout of eccentric exercise (treadmill running at 16
m.min(-1), -16 degrees incline, 90 min). RESULTS: The exercise intervention
resulted in significant increases in serum CK and AST activities in all diet
groups. Serum CK demonstrated peak activity immediately postexercise with
increases reaching 910+/-94, 594+/-53, and 283+/-52 IU.L(-1) for animals on high,
normal, and low protein diets, respectively. Similarly, peak postexercise AST
activity for high, normal, and low protein diets reached 193+/-10, 147+/-3, and
162+/-9 IU.L(-1), respectively. The exercise intervention resulted in increases
in muscle G-6-PD activity for all diet groups; however, LP rats demonstrated
significantly lower values than NP or HP rats. CONCLUSIONS: These data show that
dietary protein intake can significantly effect both serum and muscle enzyme
activity following acute exercise-induced muscle injury.
PMID- 10188747
TI - Comparison of four habitual physical activity questionnaires in girls aged 7-15
yr.
AB - PURPOSE: Questionnaires provide a practical approach to measuring physical
activity in children and adolescents, particularly for large-scale
epidemiological studies. The purpose of the present study was to compare four
habitual physical activity questionnaires and to assess their long-term
reliabilities. METHODS: Subjects were female, aged 7-15 yr (and their parents),
who participated in a cohort study in which predictors of the onset of menarche
were being investigated. Questionnaires consisted of three single-item and one
multi-item habitual physical activity questions and were sent to the 640
participants. Test-retest reliability of the questionnaires was assessed on 100
randomly selected participants 11 months later. RESULTS: The Spearman's
correlation coefficient was highest (r = 0.40) between the Godin-Shephard Score
and the Perspiration Score and was lowest (r = 0.10) between the Stairs Score and
the Specific Activity Score. The correlation coefficients were higher when the
questionnaires were reported to have been completed by the parents alone, rather
than by parents with the assistance of their daughters. The test-retest
reliabilities were r = 0.44 for the Perspiration Score, r = 0.59 for the Stairs
Score, r = 0.48 for the Godin-Shephard Score, and r = 0.53 for the Specific
Activity Score. The reliabilities were higher when the retest was reported to
have been completed by the parents alone. CONCLUSIONS: This study suggests that
the Perspiration Score, the Godin-Shephard Score, and the Specific Activity Score
may provide simple and practical measures of habitual physical activity for
children and adolescents.
PMID- 10188748
TI - Stance width and bar load effects on leg muscle activity during the parallel
squat.
AB - PURPOSE: Altering foot stance is often prescribed as a method of isolating
muscles during the parallel squat. The purpose of this study was to compare
activity in six muscles crossing the hip and/or knee joints when the parallel
squat is performed with different stances and bar loads. METHODS: Nine male
lifters served as subjects. Within 7 d of determining IRM on the squat with
shoulder width stance, surface EMG data were collected (800 Hz) from the rectus
femoris, vastus medialis, vastus lateralis, adductor longus, gluteus maximus, and
biceps femoris while subjects completed five nonconsecutive reps of the squat
using shoulder width, narrow (75% shoulder width), and wide (140% shoulder width)
stances with low and high loads (60% and 75% 1RM, respectively). Rep time was
controlled. A goniometer on the right knee was used to identify descent and
ascent phases. Integrated EMG values were calculated for each muscle during
phases of each rep, and the 5-rep means for each subject were used in a repeated
measures ANOVA (phase x load x stance, alpha = 0.05). RESULTS: For rectus
femoris, vastus medialis, and vastus lateralis, only the load effect was
significant. Adductor longus exhibited a stance by phase interaction and a load
effect. Gluteus maximus exhibited a load by stance interaction and a phase
effect. Biceps femoris activity was highest during the ascent phase. CONCLUSION:
The results suggest that stance width does not cause isolation within the
quadriceps but does influence muscle activity on the medial thigh and buttocks.
PMID- 10188749
TI - A comparison of methods for analyzing drop jump performance.
AB - PURPOSE: Drop jumping is a popular form of plyometric training. Different
techniques are applied to determine parameter values quantifying drop jumps, such
as the jump height or the durations of the phases of downward and upward
movements of the center of mass (CM) during foot contact with the ground after
dropping. The flight-time method estimates the jump height from the time between
the instant of leaving the ground and the instant of landing. In video-based
methods, markers are placed on the skin of the subject to define the positions of
the body segments. The time-dependent positions of the CM and parameter values
are then calculated utilizing models of the human body. If the vertical velocity
of the CM can be estimated at one instant, the parameter values can be calculated
from the vertical ground reaction forces. METHODS: The purpose of this study was
to find out which technique yields the lowest errors compared with the results
obtained by the double force plate technique. In this investigation, two force
plates were used, one located under the drop platform. Twenty-five drop jumps
were analyzed with eight different methods. There were large differences between
the reference method and other methods. Using the height of the drop platform
(0.39 m) to estimate the velocity at the end of the free fall, in conjunction
with data from one force plate, resulted in a mean difference of 4.2% (SD: 9.6%)
in the calculated jump height. Using video information to estimate the time that
the velocity of the CM fell to zero after the drop phase, in conjunction with
data from one force plate, resulted in differences in the jump height of up to
17%. RESULTS: Differences between the reference method and video based methods
were comparatively small (mean value of differences in jump height: -0.007 m, SD:
0.013 m for the best of these methods) but not negligible. CONCLUSIONS:
Nevertheless, video based methods turned out to be the most promising alternative
to the reference method to determine accurate variables concerning drop jump
performance.
PMID- 10188750
TI - Use of EMG analysis in challenging kinetic chain terminology.
AB - PURPOSE: The purpose of this study was to compare mean integrated
electromyographic values (EMG(int)) during biomechanically comparable closed
kinetic chain/fixed external load, open kinetic chain/moveable no load, and
moveable external load exercises. METHODS: EMG(int) were obtained for the
pectoralis major (PM) and the long head of the triceps (T) during absorption and
force phases of three biomechanically comparable exercises: the push-up (PU); the
bench press-load (BP-L); and the bench press-no load (BP-NL) equated to the
closed kinetic chain/fixed external load; moveable external load; and open
kinetic chain/moveable no load conditions respectively. A force plate was used to
equate load for the PU and BP-L exercises. Ten males (24+/-4.4 yr) participated
in the three randomly ordered exercises. A pronated, closed grip was used for all
exercises. The mean integrated EMG values from three isometric maximal voluntary
contractions were used to determine a reference EMG (EMG(MVC)) for each muscle.
Normalized EMG values (NEMG) were determined by EMG(int)/EMG(Mvc) and analyzed by
one-factor repeated measures ANOVA for each muscle (PM and T) during each phase
(absorption and force). RESULTS: There was no significant difference (P > 0.05)
between the equivalently loaded, different boundary exercises (PU and BP).
Statistical significance (P < 0.05) was determined between the differently
loaded, equivalent boundary exercises (BP and BP-NL) as well as the differently
loaded, different boundary exercises (PU and BP-NL). CONCLUSIONS: Results from
this study support the theory that activities of similar biomechanical motions
and mass of loading, regardless of the boundary condition, have comparable EMG
values of primary muscle groups. In addition, this study suggests external load
is more important than boundary condition in describing human activity.
PMID- 10188751
TI - Electromyographic timing analysis of forward and backward cycling.
AB - PURPOSE: Backward walking to running progressions are becoming a popular,
nontraditional component of functional knee rehabilitation programs. The purpose
of this electromyographic (EMG) and motion analysis study was to compare the
activation duration of the vastus medialis, vastus lateralis, rectus femoris,
medial hamstrings, lateral hamstring, tibialis anterior, and gastrocnemius
muscles during forward and backward cycling. We hypothesized that the hamstrings
would demonstrate greater activation duration during backward cycling. METHODS:
The right lower extremity of 12 healthy subjects (6 male and 6 female) was
instrumented with surface EMG electrodes and retroreflective markers to confirm
lower extremity kinematic consistency between conditions. RESULTS: Statistical
analysis of hip, knee, and ankle kinematics (200 Hz sampling rate) and gender
failed to reveal significant differences between conditions (P > 0.05). Quadrant
analysis of muscle activation duration with Bonferroni corrections for multiple
comparisons revealed that medial and lateral hamstring activation duration was
greater during the early recovery phase (quadrant III) of backward cycling than
forward cycling (P < 0.00156). Rectus femoris activation duration was greater in
the early propulsive phase of backward cycling (quadrant 1) (P < 0.00156) and in
the early recovery phase of forward cycling (quadrant III) (P < 0.00156).
CONCLUSIONS: These findings lend support for the use of backward cycling during
the early recovery phase (quadrant III) to achieve a selective hamstring muscle
response of relatively decreased patellofemoral stress and anterior cruciate
ligament strain.
PMID- 10188752
TI - Influence of resistance exercise of different intensities on state anxiety and
blood pressure.
AB - PURPOSE: The purpose of this investigation was to examine selected
psychobiological responses to acute bouts of resistance exercise (RE) of
different intensities. METHODS: Eighty-four participants were classified as
experienced or inexperienced and then randomly assigned to three conditions: 1)
50% of one repetition maximum(1RM), 2) 80% 1RM, or 3) control condition. RE
consisted of performing three sets of four exercises between 12 to 20 reps in the
50% 1RM condition and four to eight reps in the 80% 1RM condition. Dependent
variables consisted of state anxiety (SA), mood states (POMS), systolic BP (SBP),
diastolic BP (DBP), and heart rate (HR). These variables were assessed before as
well as 1, 20, 60, 120, and 180-min following the conditions. Data were analyzed
with a 2 (experience) x 3 (conditions) x 6 (trials) mixed model ANOVA and Tukey
post-hoc tests. RESULTS: Results indicated that SA decreased significantly (P <
0.05) 180 min following the 50% 1RM condition. A significant decrease (P < 0.05)
in vigor occurred immediately following the 50% IRM condition and persisted for
20 min. SBP increased significantly (P < 0.05) immediately following the 80% 1RM
condition. HR increased significantly (P < 0.05) following both RE conditions. No
significant differences were found between the experienced or inexperienced
participants. CONCLUSIONS: An acute bout of RE at 50% 1RM is associated with an
immediate reduction in vigor followed by a significant decrease in SA that
emerged 180 min following exercise.
PMID- 10188753
TI - The effect of a preexercise meal on time to fatigue during prolonged cycling
exercise.
AB - PURPOSE AND METHODS: Seven subjects exercised to exhaustion on a bicycle
ergometer at a workload corresponding to an intensity of 70% maximal oxygen
uptake (VO2max). On one occasion (FED), subjects consumed a preexercise
carbohydrate (CHO) containing breakfast (100 g CHO) 3 h before exercise. On the
other occasion (FASTED), subjects exercised after an overnight fast. Exercise
time to fatigue was significantly longer (P < 0.05) when subjects consumed the
breakfast (136+/-14 min) compared with when they exercised in the fasted state
(109+/-12 min). RESULTS: Pre- and post-exercise muscle glycogen concentrations,
respiratory exchange ratio, carbohydrate and fat oxidation, and lactate and
insulin concentrations were not significantly different between the two trials.
Insulin concentrations decreased significantly (P < 0.05) from 4.7+/-0.05
microIU.mL(-1) to 2.8+/-0.4 microIU.mL(-1) in FED and from 6.6+/-0.6 microIU.mL(
1) to 3.7+/-0.6 microIU.mL(-1) in FASTED subjects and free fatty acid
concentrations (FFA) increased significantly (P < 0.05) from 0.09+/-0.02 mmol.L(
1) to 1.4+/-0.6 mmol.L(-1) in FED and from 0.17+/-0.02 mmol.L(-) to 0.74+/-0.27
mmol.L(-1) in FASTED subjects over the duration of the trials. CONCLUSIONS: In
conclusion, the important finding of this study is the increased time to fatigue
when subjects ingested the CHO meal with no negative effects ascribed to
increased insulin concentrations and decreased FFA concentrations after CHO
ingestion.
PMID- 10188754
TI - Design and analysis of research on sport performance enhancement.
AB - PURPOSE: The purpose of this study was to assess research aimed at measuring
performance enhancements that affect success of individual elite athletes in
competitive events. ANALYSIS: Simulations show that the smallest worthwhile
enhancement of performance for an athlete in an international event is 0.7-0.4 of
the typical within-athlete random variation in performance between events. Using
change in performance in events as the outcome measure in a crossover study,
researchers could delimit such enhancements with a sample of 16-65 athletes, or
with 65-260 in a fully controlled study. Sample size for a study using a valid
laboratory or field test is proportional to the square of the within-athlete
variation in performance in the test relative to the event; estimates of these
variations are therefore crucial and should be determined by repeated-measures
analysis of data from reliability studies for the test and event. Enhancements in
test and event may differ when factors that affect performance differ between
test and event; overall effects of these factors can be determined with a
validity study that combines reliability data for test and event. A test should
be used only if it is valid, more reliable than the event, allows estimation of
performance enhancement in the event, and if the subjects replicate their usual
training and dietary practices for the study; otherwise the event itself provides
the only dependable estimate of performance enhancement. Publication of
enhancement as a percent change with confidence limits along with an analysis for
individual differences will make the study more applicable to athletes. Outcomes
can be generalized only to athletes with abilities and practices represented in
the study. CONCLUSION: estimates of enhancement of performance in laboratory or
field tests in most previous studies may not apply to elite athletes in
competitive events.
PMID- 10188755
TI - Classification of cardiorespiratory fitness without exercise testing.
AB - PURPOSE: We examined the ability of a nonexercise based VO2max, prediction model
to classify cardiorespiratory fitness (CRF) in a population of men and women aged
19-79 yr of age (N = 799). METHODS: A VO2max (mL.kg(-1).min(-1)) prediction model
was developed in the study group using multiple linear regression from the
independent variables age, age2, gender, physical activity status, height, and
body mass. The classification accuracy of this model was examined by cross
tabulating age and gender specific quintiles of measured and predicted CRF.
RESULTS: Overall classification accuracy of the model was modest (36%); however,
83% of all subjects were either classified correctly or within one quintile of
measured CRF. Extreme misclassification (e.g., misclassifying a low fit
individual as high fit) was only rarely observed (0.13%). CONCLUSIONS: The
present results support the concept that CRF prediction models can be used to
reasonably characterize the fitness level of a cohort using data that can be
obtained from a questionnaire. Accordingly, predicted CRF values may be useful as
an exposure variable in large epidemiologic studies in which exercise testing is
not feasible.
PMID- 10188756
TI - Treatment of sepsis: past and future avenues.
AB - In recent years, the concept has emerged that the host's inflammatory response
contributes substantially to the development of septic shock and organ failure.
Experimental observations prompted large scale randomised clinical trials with a
variety of agents such as glucocorticoids, ibuprofen, antiendotoxin monoclonal
antibodies, antagonists of platelet-activating factor, of bradykinin or of
interleukin-1 receptor, and monoclonal anti-tumour necrosis factor (TNF)
antibodies or soluble dimeric TNF receptor fusion proteins. All these major
studies of immunomodulators in sepsis have yielded disappointing results despite
showing promise during preliminary clinical studies. However, these recent
failures do not mean that septic shock will forever remain an insurmountable
medical challenge. Many lessons have been learned from these studies. and certain
mistakes in their study design will be avoided in the future. Our understanding
of the pathophysiology of sepsis and septic shock is increasing markedly;
potential new treatment strategies are available and could be explored to improve
the outcome of patients with sepsis.
PMID- 10188757
TI - Clinical and preclinical modulation of chemotherapy-induced toxicity in patients
with cancer.
AB - Anticancer treatment is generally associated with toxicity to health issues. One
of the reasons for this unpleasant association is that anticancer agents have
been mostly selected on the basis of an empirically established toxicity towards
cancer cell lines and rapidly growing tumours in animal models, and not on the
basis of a sophisticated intervention in tumour-specific biology. This strategy
of drug development unavoidably produces drugs with toxicity towards normal cells
and tissues which also have a high cell turnover and share many characteristics
with tumour cells. Therefore it is a continuing challenge to design therapy which
is both effective and also has high specificity for the biology of cancer and/or
is efficiently targeted to tumour tissue. This article describes the mechanisms
of cytotoxicity of standard chemo- and radiotherapy and discussed the
possibilities of currently available cytoprotective agents to reduce or prevent
these toxicities. These agents should ideally be selective for normal cells
versus cancer cells, be effective in reducing or preventing toxicity, have no
negative impact on anticancer therapy and have minimal adverse effects. None of
the agents described in this article fulfils these criteria completely and
therefore we cannot recommend these agents for standard use in daily anticancer
practice. Nevertheless, there are encouraging data concerning the beneficial
effects of dexrazoxane for anthracycline-induced cardiomyopathy and amifostine
for platinum- and radiotherapy-induced toxicity. These date warrant further
studies.
PMID- 10188758
TI - Systematic review of the treatment of early Lyme disease.
AB - Lyme disease is a rapidly emerging infectious disease and there are still many
unanswered questions with respect to appropriate laboratory tests required for
diagnosis of early Lyme disease, types of antimicrobials required for treatment
and duration of therapy. A qualitative systematic review was used to summarise
the existing data for the treatment of early Lyme disease. Eleven antibacterial
therapy trials and 3 cost-effectiveness analyses met the inclusion criteria for
this review. Antibacterial regimens that have been studied include
phenoxymethylpenicillin (penicillin V), amoxicillin, amoxicillin/probenecid,
tetracycline, doxycycline, cefuroxime axetil, erythromycin, roxithromycin,
azithromycin and ceftriaxone. The data support the use of oral beta-lactam
antibacterials [phenoxymethylpenicillin (penicillin V), amoxicillin, cefuroxime
axetil] and oral tetracyclines as effective first-line treatment modalities for
early Lyme disease. Oral macrolides are considered second-line agents as their
clinical efficacy has been less than that of the beta-lactams and tetracyclines.
Courses of therapy ranging from 10 to 21 days are supported by the available
evidence, although the optimal duration of therapy is unknown.
PMID- 10188759
TI - Preventing postoperative infections: current treatment recommendations.
AB - Surgical site infections (SSI) remain a major source of postoperative morbidity.
The preventive effect of antimicrobial drugs on postoperative infections is
without debate. The common basis of accepted indications for prophylaxis is
available evidence of effect. Valid reasons to administer antimicrobial
prophylaxis include a significant reduction of SSI or reducing the risk of SSI in
procedures where the consequences of infection are serious or even disastrous.
The antimicrobial drug must be effective against pathogens associated with
infection after a given procedure. The first generation cephalosporin, cefazolin,
has been considered one of the prophylactic drugs of choice in many authoritative
guidelines. The optimal timing of intravenous antimicrobial prophylaxis in
surgery is considered to be about 30 minutes before incision, i.e. at induction
of anaesthesia. A single dose of antimicrobial drugs before the operation is
sufficient prophylaxis for most surgical procedures. The development of bacterial
resistance is associated with antimicrobial use, and therefore prophylactic
antibiotics should be used as little as possible; in addition, the spectrum of
activity of drugs used should be as narrow as possible. Although the principles
of antimicrobial prophylaxis in surgery have been clearly established, many
reports continue to describe inappropriate drug use. Overconsumption in terms of
invalid indications or use of drugs with too broad a spectrum of activity should
be eliminated by adhering to accepted guidelines. Practical suggestions are given
to optimise timing, such as simple reminders on the daily operating programme,
the display of prophylaxis regimens according to type of surgery in table format
in the operating room and having the anaesthetist note the complete drug regimen
on the patient's anaesthesia record. Such measures will help to optimise
antibiotic prophylaxis and restrict if to the operating room where it belongs.
PMID- 10188761
TI - Basiliximab.
AB - The chimaeric monoclonal antibody basiliximab specifically binds the alpha
subunit of the interleukin-2 (IL-2) receptor on activated T lymphocytes. Through
competitive antagonism of IL-2, basiliximab supplements standard
immunosuppressive therapy after renal transplantation. < or =24 Hours after a
single intravenous dose of basiliximab 2.5 to 25 mg, approximately 90% of
available IL-2 receptors on T lymphocytes were complexed with the drug. This
level of basiliximab binding was maintained for 4 to 6 weeks when renal
transplant patients received basiliximab 20 mg 2 hours before and then 4 days
after transplantation surgery. In 2 large, well-designed trials, the percentage
of patients with biopsy-confirmed acute rejection episodes after renal
transplantation was significantly lower with basiliximab 20 mg (administered 2
hours before and then 4 days after transplantation surgery; 30 or 33%,
respectively) than placebo (44 or 46%) at 6 months after surgery. Basiliximab was
well tolerated during clinical trials. The incidence of infections (including
active cytomegalovirus infection) and post-transplant lymphoproliferative
disorders was similar with basiliximab and placebo. Cytokine release syndrome was
not observed in patients who received basiliximab.
PMID- 10188762
TI - Lamifiban.
AB - Lamifiban is an intravenously administered, selective, reversible, nonpeptide
glycoprotein IIb/IIIa receptor antagonist which inhibits platelet aggregation and
thrombus formation by preventing the binding of fibrinogen to platelets. In
trials in patients with non-Q wave myocardial infarction (MI) or unstable angina
pectoris (PARAGON A and the Canadian Lamifiban Study), the incidence of clinical
events at 30 days in patients receiving lamifiban (1 to 5 microg/min) was not
significantly different from that in patients receiving aspirin plus heparin or
aspirin alone. In PARAGON A, the incidence of clinical events at 6 months was
significantly lower after lamifiban (with or without heparin) and aspirin therapy
than after standard heparin and aspirin therapy. A large phase III trial (PARAGON
B) is under way comparing lamifiban plus aspirin and heparin with standard
aspirin and heparin therapy in patients with non-Q wave MI or unstable angina
pectoris. In clinical trials, the most common adverse events associated with
lamifiban were bleeding complications which were increased by the concomitant
administration of heparin.
PMID- 10188763
TI - Sibrafiban.
AB - Sibrafiban is the orally administered, nonpeptide, double-prodrug of Ro 44-3888
which is a selective glycoprotein IIb/IIIa receptor antagonist. It is currently
undergoing clinical trials for secondary prevention of cardiac events in patients
stabilised after acute coronary syndromes. In a phase II dose-finding study (TIMI
12) in patients stabilised after a myocardial infarction (MI) or an episode of
unstable angina, there was a dose-dependent inhibition of platelet aggregation
which correlated closely with the plasma concentration of the total active drug.
An ongoing phase III study (SYMPHONY) compares the effects of sibrafiban on
cardiac events with that of aspirin in patients stabilised after a Q wave MI or
an episode of unstable angina. This large trial uses twice daily dosage regimens
to produce the plasma concentrations which were associated with less bleeding in
the earlier dose-ranging trial. A long term (minimum duration 12 months) phase
III study (2nd SYMPHONY) is under way to compare the effects of sibrafiban on
cardiac events with those of aspirin in patients stabilised after an MI or an
episode of unstable angina. The most common adverse events associated with
sibrafiban include bleeding, with minor haemorrhages occurring more often than
with aspirin.
PMID- 10188760
TI - Current pharmacological approaches to the therapy of varicella zoster virus
infections: a guide to treatment.
AB - Varicella zoster virus (VZV), a member of the herpesvirus family, is responsible
for both primary (varicella, chickenpox) as well as reactivation (zoster,
shingles) infections. In immunocompetent patients, the course of varicella is
generally benign. For varicella zoster, post-herpetic neuralgia is the most
common complication. In immunocompromised patients (particularly those with
AIDS), transplant recipients and cancer patients, VZV infections can be life
threatening. For these patients and also for immunocompetent patients at risk
such as pregnant women or premature infants, the current treatment of choice is
based on either intravenous or oral aciclovir (acyclovir). The low oral
bioavailability of aciclovir, as well as the emergence of drug-resistant virus
strains, have stimulated efforts towards the development of new compounds for the
treatment of individuals with VZV infections. Among these new compounds,
penciclovir, its oral prodrug form famciclovir and the oral pro-drug form of
aciclovir (valaciclovir), rank among the most promising. As with aciclovir
itself, all of these drugs are dependent on the virus-encoded thymidine kinase
(TK) for their intracellular activation (phosphorylation), and, upon conversion
to their triphosphate form, they act as inhibitors/alternative substrate of the
viral DNA polymerase. Therefore, cross-resistance to these drugs may be expected
for those virus mutants that are TK-deficient and thus resistant to aciclovir.
Other classes of nucleoside analogues dependent for their phosphorylation on the
viral TK that have been pursued for the treatment of VZV infections include
sorivudine, brivudine, fialuridine, fiacitabine and netivudine. Among
oxetanocins, which are partially dependent on viral TK, lobucavir is now under
clinical evaluation. Foscarnet, which does not require any previous metabolism to
interact with the viral DNA polymerase, is used in the clinic when TK-deficient
VZV mutants emerge during aciclovir treatment. TK-deficient mutants are also
sensitive to the acyclic nucleoside phosphonates (i.e. [s]-1-[3-hydroxy-2
phosphonylmethoxypropyl]cytosine; HPMPC); these agents do not depend on the virus
encoded TK for their phosphorylation but depend on cellular enzymes for
conversion to their diphosphoryl derivatives which then inhibit viral DNA
synthesis. Vaccination for VZV has now come of age. It is recommended for healthy
children, patients with leukaemia, and patients receiving immunosuppressive
therapy or those with chronic diseases. The protection induced by the vaccine
seems, to some extent, to include zoster and associated neuralgia. Passive
immuniatin based on specific immunoglobulins does not effectively prevent VZV
infection and is therefore restricted to high risk individuals (i.e.
immunocompromised children and pregnant women).
PMID- 10188765
TI - Isosorbide 5-mononitrate: a review of a sustained-release formulation (Imdur) in
stable angina pectoris.
AB - Imdur (IMD) is a sustained-release isosorbide 5-mononitrate preparation for the
treatment of chronic stable angina pectoris. Controlled medication release is
achieved using the Durules principle of insoluble matrix embedding. Data from
randomised double-blind trials show that IMD 60 mg once daily (the most widely
studied dosage) has significant antianginal and anti-ischaemic effects compared
with placebo after 2 weeks' treatment. Efficacy was generally observed
approximately 1 to 12 hours after administration, indicating that once-daily
administration in the morning will provide effective prophylaxis of symptoms
throughout the day. Improvements from baseline are generally maintained during
IMD repeated treatment. There was no evidence of classical tolerance to IMD 30 to
240 mg/day in a large well designed study. Although improvements from baseline
were maintained over 6 weeks with IMD 30 or 60 mg/day, statistical significance
versus placebo was eventually lost because of improved performance in the placebo
group. IMD 120 or 240 mg/day were more effective than placebo after 6 weeks.
Studies lasting up to 2 weeks found no evidence of tolerance to IMD 60 mg/day. In
comparative trials lasting approximately 2 weeks, IMD 60 mg once daily was more
effective than isosorbide dinitrate 30 mg 4 times daily and similar to or better
than isosorbide dinitrate 20 mg 3 times daily. Preliminary data show that IMD 60
mg once daily has similar efficacy to diltiazem 60 mg 3 times daily and is at
least as effective as certain other sustained-release isosorbide 5-mononitrate
preparations. There is no evidence for rebound worsening of ischaemia 24 hours
after IMD administration. Abrupt discontinuation during long term IMD treatment
may exacerbate anginal symptoms. In general, IMD is well tolerated. The most
frequently reported adverse event, headache, is usually mild to moderate,
improves with long term therapy and rarely leads to treatment withdrawal. Patient
compliance is better with once-daily administration of IMD than with twice-daily
administration of conventional isosorbide 5-mononitrate. CONCLUSIONS: In patients
with chronic stable angina, IMD provides effective antianginal prophylaxis for up
to 12 hours and does not seem to be associated with rebound phenomena at the end
of the dosage interval. Improvements from baseline are maintained during repeated
administration, although loss of statistically significant superiority over
placebo was evident during 6 weeks' treatment with IMD < or =60 mg/day in 1
study. Further evaluation of comparative efficacy (particularly with respect to
other sustained-release preparations) and long term effects would be beneficial.
Nevertheless, the available data suggest that IMD is a useful and convenient
agent for the treatment of patients with chronic stable angina pectoris.
PMID- 10188766
TI - The effects of injury on the adaptive immune response.
AB - For more than thirty years it has been apparent that serious injury in humans and
experimental animals is associated with a decrease in immune functions dependent
upon T cells, the principal cells involved in initiating adaptive immune
responses. This review focuses on more recent evidence that T helper cell
function is altered after serious injury with loss of T helper 1 function and
cytokine production and with preservation of T helper 2 function and an increased
production of T helper 2 cytokines. Emphasis is placed on the importance of
interactions between the innate and adaptive immune systems in the perturbed
immune responses seen following injury. Immunomodulatory strategies are mentioned
that have had success in animal models in ameliorating the diminished resistance
to infection commonly seen after major traumatic or thermal injury. Finally, it
is emphasized that immunomodulatory treatments that are successful in preventing
infection may be contraindicated once infection is manifest.
PMID- 10188764
TI - Aprotinin: an update of its pharmacology and therapeutic use in open heart
surgery and coronary artery bypass surgery.
AB - Cardiopulmonary bypass (CPB) is associated with defective haemostasis which
results in bleeding and the requirement for allogenic blood product transfusions
in many patients undergoing open heart surgery (OHS) and/or coronary artery
bypass graft surgery (CABG) with CPB. Conservation of blood has become a priority
during surgery because of shortages of donor blood, the risks associated with the
use of allogenic blood products and the costs of these products. Aprotinin is a
serine protease inhibitor isolated from bovine lung tissue which acts in a number
of interrelated ways to provide an antifibrinolytic effect, inhibit contact
activation, reduce platelet dysfunction and attenuate the inflammatory response
to CPB. It is used to reduce blood loss and transfusion requirements in patients
with a risk of haemorrhage and has clear advantages over placebo or no treatment.
High dose aprotinin significantly reduces postoperative blood loss compared with
aminocaproic acid and desmopressin, and decreases transfusion requirements
compared with desmopressin. Results are less consistent with tranexamic acid:
high dose aprotinin either reduces blood loss significantly more than, or to an
equivalent level to, tranexamic acid. A variety of other lower aprotinin dosage
regimens consistently result in similar reductions in blood loss to aminocaproic
acid or tranexamic acid. Data from clinical trials indicate that aprotinin is
generally well tolerated, and the adverse events seen are those expected in
patients undergoing OHS and/or CABG with CPB. Hypersensitivity reactions occur in
<0.1 to 0.6% of patients receiving aprotinin for the first time. The results of
original reports indicating that aprotinin therapy may increase myocardial
infarction rates or mortality have not been supported by more recent studies
specifically designed to investigate this outcome. However, a tendency to early
vein graft occlusion with aprotinin has been shown and care with anticoagulation
and vessel grafts is required. No comparative tolerability data between aprotinin
and the lysine analogues, aminocaproic acid and tranexamic acid, are available.
CONCLUSION: Comparative tolerability and cost-effectiveness data for aprotinin
and the lysine analogues are required to more fully assess their individual roles
in reducing blood loss and transfusion requirements in patients undergoing CPB
during OHS and/or CABG. However, clinical evidence to date supports the use of
aprotinin over its competitors in patients at high risk of haemorrhage, in those
for whom transfusion is unavailable or in patients who refuse allogenic
transfusions.
PMID- 10188767
TI - Circulating endothelin and nitrate-nitrite relate to hemodynamic and metabolic
variables in human septic shock.
AB - Activation of the nitric oxide (NO) pathway over that of endothelin in the vessel
wall, as judged from circulating endothelin and nitrate-nitrite (NN) levels, may
partly account for the hypotension associated with vasodilation, diminished
catecholamine sensitiveness and O2 extraction, and lactic acidemia in human
septic shock. In a prospective study, 14 consecutive patients with septic shock
and a pulmonary artery catheter in place were included. For 3 days after
admission, serial measurements of hemodynamic variables and plasma levels of
endothelin and NN were done. The patients had a hyperdynamic circulation. Except
for a higher final blood lactate level and more treatment with vasoconstricting
catecholamines in nonsurvivors, global hemodynamic and O2-related variables did
not differ between outcome groups. On the day of admission, circulating
endothelin and NN levels were elevated and related to elevated levels of tumor
necrosis factor-alpha and interleukin-6. The levels of endothelin increased in
time in nonsurvivors as compared with survivors. The NN levels declined in
survivors but not in nonsurvivors. The systemic vascular resistance indices
(SVRI), global O2 extraction ratios, and blood lactate levels directly related to
the endothelin levels. SVRI and global O2 extraction ratios inversely, and the
lactate blood levels directly, related to NN levels, and the hemodynamic and
metabolic parameters related directly to the ratio between endothelin and NN
plasma levels on the days of the study. The vessel wall factors did not relate to
the creatinine levels. The results suggest that the hemodynamic and metabolic
peripheral abnormalities of human septic shock are mediated in part by cytokine
activated endothelin and NO systems in the vessel wall. They also suggest that
increased production rather than diminished renal clearance accounts for elevated
levels of NN and endothelin and that the latter are associated with a poor
outcome.
PMID- 10188768
TI - Circulating granulocyte macrophage colony-stimulating factor in plasma of
patients with the systemic inflammatory response syndrome delays neutrophil
apoptosis through inhibition of spontaneous reactive oxygen species generation.
AB - In the normal resolution of an acute inflammatory response apoptosis of
neutrophils is essential to maintain immune homeostasis and limit inappropriate
host tissue damage by decreasing neutrophil tissue load, function, and release of
phlogistic reactive oxygen species and proteases. The systemic inflammatory
response syndrome (SIRS), a massive pro-inflammatory immune state, is associated
with delayed neutrophil apoptosis, however, the systemic circulating factors and
intracellular signal transduction pathways important in regulating neutrophil
apoptosis in SIRS are poorly described. Neutrophils isolated from patients with
SIRS on admission to the intensive care unit showed significantly (p<.01) delayed
spontaneous neutrophil apoptosis compared with healthy neutrophils as quantified
using annexin V-FITC and terminal deoxyuridine triphosphate (dUTD) nick end
labeling (TUNEL) flow cytometry methods. Plasma from SIRS patients markedly
(41.5+/-7.2%, p<.01) inhibited apoptosis of healthy neutrophils compared with
controls (69.7+/-4.8%) indicating the presence of soluble circulating factors
that can modify the expression of neutrophil apoptosis. Various pro-inflammatory
(IL-6, granulocyte macrophage colony-simulating factor, interleukin (IL)-1beta,
tumor necrosis factor-alpha) mediators, known to modulate neutrophil apoptosis in
vitro, were elevated in the plasma of our cohort of SIRS patients compared with
controls. However, the anti-apoptotic effect of SIRS plasma was specifically
attenuated (75.5%, p<.01) by neutralizing SIRS plasma of granulocyte macrophage
colony-stimulating factor, but not IL-6, IL-1beta, tumor necrosis factor-alpha.
Although the anti-inflammatory cytokine IL-10 was elevated in SIRS plasma (median
level 7.2 pg/mL), further boosting SIRS plasma with recombinant human IL-10 (10
ng/mL, levels found in septic shock patients) significantly countered (63.8%,
p<.01) the inhibitory effect of SIRS plasma on neutrophil apoptosis. Suppression
of neutrophil apoptosis was concomitant with delayed spontaneous elevation of
reactive oxygen species, quantified as peroxide production, and reversed by
addition of neutralizing antibodies to GM-CSF, and recombinant human IL-10 to
SIRS plasma. These results identify circulating GM-CSF as a significant inhibitor
of neutrophil apoptosis in patients with SIRS, and that this effect can be
countered by boosting SIRS plasma with IL-10. GM-CSF and IL-10 appear to modulate
neutrophil apoptosis by altering reactive oxygen species generation in
neutrophils.
PMID- 10188769
TI - Patterns of vasoregulatory gene expression in the liver response to
ischemia/reperfusion and endotoxemia.
AB - Oxidative stress and inflammatory reactions associated with stresses that may
lead to shock promote hepatic microcirculatory dysfunction, which may lead to
hepatic injury. Because altered liver microcirculation may result from an
imbalance in the expression of stress-induced vasoactive mediators, our study was
conducted to investigate changes in the expression of genes encoding endothelin-1
(ET-1), its receptors, ET(A) and ET(B), heme-oxygenase 1 (HO-1), and inducible
nitric oxide synthase (iNOS), using two different rat models of liver stress:
ischemia/reperfusion of the liver and lipopolysaccharide (LPS)-induced
endotoxemia. In ischemia/reperfusion experiments, rats were subjected to 1 h
hepatic ischemia, followed by 6 h of reperfusion. Endotoxemia was induced by i.p.
injection of LPS (1 mg/mL/kg body weight); rats were studied after 6 h. mRNA
levels were estimated using semiquantitative reverse transcriptase-polymerase
chain reaction (RT-PCR) on total RNA samples prepared from experimental and sham
control rat livers. In the ischemic reperfused livers the levels of mRNA for ET
1, ET(B), HO-1, and iNOS were significantly elevated. The fold increase versus
sham was 2.5+/-1.1 (ET-1), 2.1+/-1.3 (ET(B)), 2.1+/-.8 (HO-1), and 6.4+/-3.9
(iNOS). In contrast, the expression of ET(A) receptor gene was reduced after
ischemia/reperfusion (to 73+/-1% of sham). In the separate experiments we
analyzed the same mRNAs levels after 1 h of ischemia (no reperfusion), and did
not detect any changes. During endotoxemia we observed a marked increase in iNOS
mRNA level (>24-fold), as well as a marked elevation of the other four mRNAs. The
fold increase versus sham was 6.1+/-1.7, ET-1); 1.5+/-.3 (ET(A)); 1.6+/-.4
(ET(B)); and 2.4+/-.34 (HO-1). These results show that liver stress, induced by
ischemia/reperfusion or LPS injection have characteristic patterns of
vasoregulatory genes expression indicating that, although both stresses result in
an increase in specific vascular reactivity, different pathways are involved in
inducing the hepatic vascular stress response.
PMID- 10188770
TI - Escherichia coli lipopolysaccharide potentiation and inhibition of rat neonatal
microglia superoxide anion generation: correlation with prior lactic
dehydrogenase, nitric oxide, tumor necrosis factor-alpha, thromboxane B2, and
metalloprotease release.
AB - The effects of lipopolysaccharide (LPS) on the central nervous system, one of the
first organs to be affected by sepsis, are still incompletely understood. Rat
microglia (BMphi) constitute the main leukocyte-dependent source of reactive
oxygen species in the central nervous system. The in vitro effect of LPS on
agonist-stimulated superoxide (O2-) generation from BMphi appears controversial.
Our purpose was to determine the time- and concentration-dependent effect of
Escherichia coil LPS on phorbol-12 myristate 13-acetate-stimulated O2- generation
from BMphi. Our results demonstrate that BMphi O2- generation in vitro peaked 17
h after stimulation of with .3 ng/mL LPS. Furthermore, stimulation of BMphi with
LPS for 17 h resulted in the following concentration-dependent responses: .1-1
ng/mL LPS induced no prior mediator generation but potently enhanced subsequent
phorbol-12 myristate 13-acetate-stimulated O2- generation; 3-10 ng/mL LPS caused
nitric oxide, tumor necrosis factor-alpha (TNF-alpha), thromboxane B2 and matrix
metalloproteinase-9 release although partially inhibiting ensuing phorbol-12
myristate 13-acetate-stimulated O2- generation; 30-100 ng/mL LPS, maximized
nitric oxide, TNF-alpha, thromboxane B2, matrix metalloproteinase-9 generation
with concomitant lactic dehydrogenase release although strongly deactivating
successive phorbol-12 myristate 13-acetate-stimulated O2 production. Our in vitro
studies suggest that enhanced release of these four mediators (nitric oxide, TNF
alpha, thromboxane B2, and matrix metalloproteinase-9) during stimulation of
BMphi with LPS might play a critical role in the subsequent ability of BMphi to
generate O2- in vivo. Potential clinical implications of our findings are
suggested by the fact that LPS levels similar to the ones used in this study have
been observed in cerebrospinal fluid both in Gram-negative meningitis and sepsis.
PMID- 10188771
TI - Power spectral analysis of arterial and central venous pressure signals during
graded hemorrhage in anesthetized rats.
AB - Based on simultaneous power spectral analysis of systemic arterial pressure (SAP)
and central venous pressure (CVP) signals in rats anesthetized with pentobarbital
sodium, we assessed the hypotheses that subtle changes in the SAP spectrum exist
during hemorrhagic shock, and that the CVP spectrum is a feasible index for
central blood volume during acute graded blood loss. During Stage I hemorrhagic
shock seen after reduction in 10% of total blood volume (TBV), there was a
significant increase in the power of both the very low frequency (VLF, 0-.25 Hz)
and low frequency (LF, .25-.8 Hz) components, along with a moderate decrease in
the very high frequency (VHF, 5-9 Hz) component, of SAP signals. Substantial
reduction in VLF, LF, and VHF components in the SAP spectrum occurred after a
blood loss of 25% of TBV (Stage II), which persisted during Stage III hemorrhagic
shock when the withdrawn blood reached 50% of TBV and the mean SAP maintained at
40 mm Hg. The depressed SAP-VLF and SAP-LF components sustained the period of
spontaneous recovery and subsequent retransfusion of shed blood, although the
power of SAP-VHF component gradually elevated during these two periods. The power
of the high-frequency (HF, .8-2.4 Hz) component of SAP signals increased
discernibly only during Stage III, became significant on spontaneous recovery,
and declined during retransfusion. Although CVP and CVP-VHF component
progressively declined, the power of the CVP-HF component manifested a gradual
increase that was significantly and reversely correlated with the reduction in
TBV. We conclude that differential changes in individual components of the SAP
spectrum occur during hemorrhagic shock, and that the CVP-HF component may be a
reliable indicator for central blood volume during acute graded blood loss.
PMID- 10188772
TI - Oxyradical-mediated hepatocellular Ca2+ alterations during hemorrhagic shock and
resuscitation.
AB - Both altered Ca2+ homeostasis and injury by oxygen-free radicals (OFR) are
pivotal mechanisms of cellular dysfunction. The purpose of this study was to
evaluate the role of OFR and xanthine oxidase in hepatocellular Ca2+
dysregulation following hemorrhagic shock and resuscitation. Anesthetized rats
were bled to a mean arterial blood pressure of 40 mm Hg for 60 min and then
resuscitated with 60% of shed blood and 3-fold the shed blood volume as lactated
Ringer's for another 60 min. Total Ca2+ uptake (Ca2+(up)), rate of Ca2+ influx
(Ca2+(in)), and membrane Ca2+(flux) (Ca2+(flux)) were determined in isolated
hepatocytes using 45Ca2+ incubation techniques. Hepatocyte oxidant injury was
fluorometrically determined by thiobarbituric acid-reactive substances, oxidized,
and reduced glutathione. Hemorrhage/resuscitation significantly increased
Ca2+(up), Ca2+(in), and Ca2+(flux) compared with sham-operated rats. Continuous
administration of superoxide dismutase or catalase (60,000 IU/kg body weight)
during resuscitation substantially decreased Ca2+(up), Ca2+(in), Ca2+(flux), and
oxidant injury. Pretreatment with allopurinol (50 mg/kg/day for 2 days)
significantly inhibited enhanced plasma xanthine oxidase activity and hepatocyte
glutathione oxidation, however, it did not prevent hepatocellular Ca2+
dysregulation. These data suggested a significant role of oxyradicals in
ischemia/reperfusion-induced Ca2+ overload, however, xanthine oxidase activation
seemed not to be a main source of these radicals.
PMID- 10188773
TI - Reduced arginine plasma levels are the drive for arginine production by the
kidney in the rat.
AB - In bile duct ligated rats, arginase (ASE) release from damaged hepatocytes
results in low arginine (ARG) levels despite maximal renal ARG production. Plasma
ARG levels were restored by reducing gut-derived endotoxemia that lowered
circulating ASE activity although maintaining increased renal production. From
this it was not clear if the higher renal ARG production was induced by the low
grade endotoxemia or the low arginine plasma levels. The separate and combined
influence of both factors on ARG metabolism was studied in the rat. Male Wistar
rats received either bovine liver ASE, to lower ARG levels, or saline (SAL).
Following the ASE or SAL infusion, rats were randomized to receive a low dose
endotoxin (LPS) or SAL infusion. In ASE/SAL- and ASE/LPS-treated rats, ARG levels
were lower compared with SAL/SAL (p<.005) and SAL/LPS (p<.005). The increased ARG
production by the kidneys and gut proved to be independent of LPS but related to
reduced ARG plasma levels (both p<.05 when compared with SAL/SAL and SAL/LPS).
Metabolism of related amino acids was not explanatory. The study concluded that a
low grade endotoxemia did not influence the metabolism of ARG by the gut, kidney,
and liver. Reductions in ARG plasma by ASE treatment, irrespective a low dose
endotoxin, were the drive for ARG production by the gut and the kidney.
PMID- 10188774
TI - Intrinsic myocardial function in hemorrhagic shock.
AB - Hemorrhage is a stress on the cardiovascular system that results in decreased
loading of the heart but also decreased blood pressure and thus decreased
perfusion pressure for tissue blood flow. The heart's response to hemorrhage is
governed by both an increase in sympathetic nervous system activation of the
heart and decreased preload and afterload for the heart. Whether the heart can
maintain normal contractile function and reserves under conditions of prolonged
hemorrhagic shock is not clear. To assess the effects of hemorrhagic shock of
different lengths on intrinsic cardiac contractile function, guinea pigs were
surgically prepared for the measurement of blood pressure, heart rate, and
cardiac output and blood samples were taken for the measurement of metabolic
indices of cardiovascular stress. Fifty percent of the animals' blood volume was
removed and then animals were followed for 1, 2, or 3 h of hemorrhagic shock.
Hearts were then removed for measurement of intrinsic contractile function.
Hearts from animals exposed to 1 or 2 h of shock exhibited normal ventricular
function although hearts removed after 3 h exhibited changes in ventricular
function. Maintenance of normal cardiac function through at least 2 h of shock
must represent adequate physiologic modulation of coronary blood flow to deliver
adequate oxygen to match the myocardial oxygen demands under conditions of severe
blood loss. This balance may be disrupted by 3 h of shock thus resulting in loss
of contractile reserve.
PMID- 10188775
TI - Does Fas ligand or endotoxin contribute to thymic apoptosis during polymicrobial
sepsis?
AB - Recent studies have shown that with the onset of sepsis there is an increase in
apoptosis (Ao) in the thymus, mediated in part by steroids, which may contribute
to a loss of T-cell progenitors, thereby, reducing immune functions. However,
reports also suggest that these steroid effects could be mediated by Fas ligand
(FasL) and/or by endotoxin (ETX). Thus, our study was to determine: 1) if
polymicrobial sepsis (cecal ligation and puncture; CLP) alters thymocyte Fas
antigen/receptor (Fas+) expression and 2) if the increase in Ao in septic ETX
sensitive C3H/HeN mice is seen in thymocytes from ETX-tolerant, C3H/HeJ, or the
FasL-deficient/ETX-tolerant, C3H/HeJ-FasL(gld), male mouse strains subjected to
CLP or sham-CLP (Sham) 12 or 24 h before they were killed. The results of flow
cytometric analysis indicated that increased %Ao+ seen in thymocytes of CLP
C3H/HeN mice was associated with either no change (12 h) or a decrease in %Fas+
expression at 24 h, although the %Bcl-2+ (an antiapoptotic protein) cells was
depressed at both times. Additional studies examining C3H/HeJ or C3H/HeJ
FasL(gld) mice subjected to CLP show that as with the ETX-sensitive mouse,
thymocyte Fas and Bcl-2 antigen expression as well as Bcl-2/Bcl-X(L/S) mRNA
levels decreased although the %Ao+ increased after CLP in both ETX-tolerant and
ETX-tolerant/FasL-deficient mice. Furthermore, if ETX-tolerant/FasL-deficient CLP
animals were administered the steroid receptor antagonist RU-38486 (s.c.,
immediately after CLP) the increase in Ao was markedly attenuated, along with
restoration of the percentage of cells expressing Bcl-2 and Fas antigen as well
as Bcl-2/Bcl-X(L/S) mRNA levels. Thus, we concluded that increased septic
thymocyte Ao is not regulated through either Fas mediated pathway or ETX, but is
a result of the release of endogenous steroids possibly acting directly or
indirectly on Bcl-2 expression.
PMID- 10188776
TI - Effect of amiloride on age-dependent cardiac dysfunction after
ischemia/reperfusion in the isolated, perfused rat heart.
AB - This study was intended to compare the cardiac consequences of
ischemia/reperfusion and amiloride treatment in immature (2-3 wk), juvenile (4-6
wk), and adult (3-5 mo) rats using an isolated, perfused heart model. Male
immature, juvenile, and adult rats were anticoagulated and anesthetized. Hearts
were harvested and coronary arteries were perfused on a Langendorff apparatus via
retrograde perfusion of the aorta at a constant coronary flow (initially
determined by perfusing the heart at 50 mm Hg perfusion pressure) with oxygenated
Krebs-Henseleit-Bicarbonate (KHB) solution. Left ventricular peak systolic
(LVPSP) and end diastolic (LVEDP) pressures were measured via a balloon-tipped
catheter placed in the left ventricle through the mitral valve. Following a 20-30
min stabilization period, hearts underwent 30 min of normothermic ischemia and
were then reperfused with Krebs-Henseleit-Bicarbonate alone for 30 min, or Krebs
Henseleit-Bicarbonate containing 500 microM amiloride for 5 min followed by Krebs
Henseleit-Bicarbonate alone for 25 min (n = 6/age group). Left ventricular
generated pressure was calculated (left ventricular peak systolic-left
ventricular end diastolic) and used as a measure of ventricular function. All
hearts demonstrated a decrease in generated pressure, respectively, from
preischemic levels at 15 and 30 min of reperfusion, although this decrease was
significantly less for the immature hearts. Ischemia/reperfusion injury was
attenuated by amiloride in adult and juvenile hearts, whereas
ischemia/reperfusion injury was worsened by amiloride in immature hearts.
Although immature hearts were relatively resistant to ischemia/reperfusion injury
compared with adult and juvenile hearts, the presence of amiloride during
reperfusion resulted in more severe ventricular dysfunction in immature hearts.
These data suggest a differential age-dependent mechanism of sarcolemmal ion
exchange in response to ischemia/reperfusion.
PMID- 10188777
TI - From mouse to man: or what have we learned about cytokine-based anti-inflammatory
therapies?
PMID- 10188778
TI - The background of the muscarinic system.
PMID- 10188779
TI - Muscarinic agonists as analgesics. Antinociceptive activity versus M1 activity:
SAR of alkylthio-TZTP's and related 1,2,5-thiadiazole analogs.
AB - Alkylthio-TZTPs (3-(3-alkylthio-1,2,5-thiadiazol-4-yl)-1,2,5,6-tetrahydro-1-met
hylpyridines) and corresponding azabicyclic analogs were tested for m1 efficacy
in cloned human m1 receptors and for antinociceptive activity in the mouse grid
shock assay. The m1 (%PI) SAR were distinctly different from the analgesia and
the salivation SAR, suggesting that analgesia is mediated by neither m1 nor M3
muscarinic receptors.
PMID- 10188780
TI - The design and pharmacology of novel selective muscarinic agonists and
antagonists.
AB - The muscarinic pharmacology of C1-methyl-substituted chiral compounds related to
McN-A-343 and of (R)- and (S)-dimethindene has been studied. Among the McN-A-343
analogues, the (S)-enantiomers were more potent and had higher affinity than the
(R)-isomers. The quaternary compound (S)-BN 228 was found to be the most potent
M1-selective agonist known today (pEC50: M1/rabbit vas deferens = 7.83; M2/guinea
pig atria = 6.35; M3/guinea-pig ileum = 6.29). In both the atria and ileum the
tertiary carbamate, (S)-4-F-MePyMcN, was a competitive antagonist (pA2 value =
7.39 and 6.82, respectively). In contrast, in rabbit vas deferens (S)-4-F-MePyMcN
was a potent partial agonist (pEC50 = 7.22; apparent efficacy = 0.83). These
results indicate that (S)-4-F-MePyMcN might be a useful tool to study M1 receptor
mediated effects involved in central cholinergic function. (S)-Dimethindene was a
potent M2-selective antagonist (pA2 = 7.86/atria; pKi = 7.8/rat heart) with lower
affinities for the M1 (pA2 = 6.36/rat duodenum; pKi = 7.1/NB-OK 1 cells), M3 (pA2
= 6.92/guinea-pig ileum; pKi = 6.7/rat pancreas) and M4 receptors (pKi = 7.0/rat
striatum). It was more potent (up to 41-fold) than the (R)-isomer. In contrast,
the stereoselectivity was inverse at ileal H1 receptors (pA2: (R)-isomer = 9.42;
(S)-isomer = 7.48). Thus, (S)-dimethindene could be a valuable agent to test the
hypothesis that M2 antagonists show beneficial effects in the treatment of
cognitive disorders. It might also become the starting point for the development
of diagnostic tools for quantifying M2 receptors in the CNS with PET imaging.
PMID- 10188782
TI - Quinuclidin-2-ene-based muscarinic antagonists.
AB - A series of achiral 3-heteroaryl substituted quinuclidin-2-ene derivatives and
related compounds have been synthesized by facile methods. The compounds were
evaluated for muscarinic and antimuscarinic properties in receptor binding
studies using (-)-[3H]-QNB as the radioligand and in a functional assay using
isolated guinea pig urinary bladder. 3-(2-Benzofuranyl)-quinuclidin-2-ene (15)
displayed the highest M1-receptor affinity in the present series (Ki = 9.6 nM).
PMID- 10188781
TI - Molecular probes for muscarinic receptors: functionalized congeners of selective
muscarinic antagonists.
AB - The muscarinic agonist oxotremorine and the tricyclic muscarinic antagonists
pirenzepine and telenzepine have been derivatized using a functionalized congener
approach for the purpose of synthesizing high affinity ligand probes that are
suitable for conjugation with prosthetic groups, for receptor cross-linking,
fluorescent and radioactive detection, etc. A novel fluorescent conjugate of TAC
(telenzepine amine congener), an n-decylamino derivative of the m1-selective
antagonist, with the fluorescent trisulfonated pyrene dye Cascade Blue may be
useful for assaying the receptor as an alternative to radiotracers. In a rat m3
receptor mutant containing a single amino acid substitution in the sixth
transmembrane domain (Asn507 to Ala) the parent telenzepine lost 636-fold in
affinity, while TAC lost only 27-fold. Thus, the decylamino group of TAC
stabilizes the bound state and thus enhances potency by acting as a distal anchor
in the receptor binding site. We have built a computer-assisted molecular model
of the transmembrane regions of muscarinic receptors based on homology with the G
protein coupled receptor rhodopsin, for which a low resolution structure is
known. We have coordinated the antagonist pharmacophore (tricyclic and piperazine
moieties) with residues of the third and seventh helices of the rat m3 receptor.
Although the decylamino chain of TAC is likely to be highly flexible and may
adopt many conformations, we located one possible site for a salt bridge
formation with the positively charged -NH3+ group, i.e. Asp113 in helix II.
PMID- 10188783
TI - The design of novel methoctramine-related tetraamines as muscarinic receptor
subtype selective antagonists.
AB - Several novel methoctramine-related tetraamines were designed, and their
biological profiles at muscarinic receptor subtypes were assessed by functional
experiments in isolated guinea pig and rat atria (M2) and smooth muscle (ileum
and trachea, M3) and by binding assays in rat cortex (M1), heart (M2), and
submaxillary gland (M3) homogenates and NG 108-15 cells (M4). Tripitramine, a
nonsymmetrical tetraamine, resulted in the most potent and the most selective
muscarinic M2 receptor antagonist of the series (pA2 = 9.14-9.85; pKi = 9.54).
Spirotramine (FC 15-94), a symmetrical tetraamine, was able to differentiate
between muscarinic M1 receptors (pKi = 7.88) and the other subtypes (M2, pKi =
6.20; M3, pKi = 5.81; M4, pKi = 6.27). Thus, tripitramine and spirotramine could
be valuable tools for the pharmacological classification and characterization of
muscarinic receptor subtypes.
PMID- 10188784
TI - In vitro and in vivo evaluation of the subtype-selective muscarinic agonist PD
151832.
AB - PD 151832 is a potent partial muscarinic agonist that displays a high level of
functional selectivity for the muscarinic m1 receptor subtype, as evidenced by
its selective stimulation of PI turnover and cellular metabolic activity in
transfected Hm1-CHO cells at concentrations that produce minimal stimulation of
other cloned human muscarinic receptors. PD 151832 enhanced the amplification of
Hm1-transfected NIH-3T3 cells at concentrations lower than those required to
produce similar effects in Hm2 or Hm3-transfected cells. The functional m1
selectivity of PD 151832 is consistent with its improvement of mouse water maze
performance at doses far lower than those required to produce peripheral
parasympathetic side effects.
PMID- 10188785
TI - Tiotropium bromide (Ba 679 BR), a novel long-acting muscarinic antagonist for the
treatment of obstructive airways disease.
AB - Tiotropium bromide (Ba 679 BR) is a novel potent and long-lasting muscarinic
antagonist that has been developed for the treatment of chronic obstructive
airways disease (COPD). Binding studies with [3H]tiotropium bromide in human lung
have confirmed that this is a potent muscarinic antagonist with equal affinity
for M1-, M2- and M3-receptors and is approximately 10-fold more potent than
ipratropium bromide. Tiotropium bromide dissociates very slowly from lung
muscarinic receptors compared with ipratropium bromide. In vitro tiotropium
bromide has a potent inhibitory effect against cholinergic nerve-induced
contraction of guinea-pig and human airways, that has a slower onset than
atropine or ipratropium bromide. After washout, however, tiotropium bromide
dissociates extremely slowly compared with the dissociation of atropine and
ipratropium bromide. Measurement of acetylcholine (ACh) release from guinea-pig
trachea shows that tiotropium bromide, ipratropium bromide and atropine all
increase ACh release on neural stimulation and that this effect is washed out
equally quickly for the three antagonists. This confirms binding studies to
transfected human muscarinic receptors which suggested that tiotropium bromide
dissociates slowly from M3-receptors (on airway smooth muscle) but rapidly from
M2 autoreceptors (on cholinergic nerve terminals). Clinical studies with inhaled
tiotropium bromide confirm that it is a potent and long-lasting bronchodilator in
COPD and asthma. Furthermore, it protects against cholinergic bronchoconstriction
for > 24 h. This suggests that tiotropium bromide will be a useful
bronchodilator, particularly in patients with COPD, and may be suitable for daily
dosing. The selectivity for M3- over M2-receptors may also confer a clinical
advantage.
PMID- 10188786
TI - Pre-clinical and clinical pharmacology of selective muscarinic M3 receptor
antagonists.
AB - Muscarinic M3 receptor antagonists have therapeutic potential for the treatment
of disorders associated with altered smooth muscle contractility or tone. These
include irritable bowel syndrome (IBS), chronic obstructive airways disease
(COAD) and urinary incontinence. Zamifenacin is a potent muscarinic receptor
antagonist on the guinea pig ileum (pA2 value 9.27) with selectivity over M2
receptors in the atria (135-fold) and M1/M4 receptors in the rabbit vas deferens
(78-fold). In addition, zamifenacin had lower affinity for the M3 receptor in the
salivary gland (pKi 7.97). In animals, zamifenacin potently inhibited gut
motility in the absence of cardiovascular effects and with selectivity over
inhibition of salivary secretion. In healthy volunteers, zamifenacin inhibited
small and large bowel motility and increased the rate of gastric emptying over a
dose range which was associated with minimal anticholinergic side effects. These
data show that zamifenacin, a selective muscarinic M3 receptor antagonist, was
well tolerated in man and was efficacious as an inhibitor of gut motility.
Further studies in patients are required with muscarinic M3 receptor antagonists
to confirm efficacy against symptoms in diseases associated with altered smooth
muscle contractility.
PMID- 10188787
TI - Differential alterations in muscarinic receptor subtypes in Alzheimer's disease:
implications for cholinergic-based therapies.
AB - Molecular subtypes of muscarinic receptors (m1-m5) are novel targets for
cholinergic replacement therapies in Alzheimer's disease (AD). However, knowledge
concerning the relative distribution, abundance and functional status of these
receptors in human brain and AD is incomplete. Recent data from our laboratory
have demonstrated a defect in the ability of the M1 receptor subtype to form a
high affinity agonist-receptor-G protein complex in AD frontal cortex. This
defect is manifested by decreased M1 receptor-stimulated GTPgammaS binding and
GTPase activity and by a loss in receptor-stimulated phospholipase C activity.
Normal levels of G proteins suggest that the aberrant receptor-G protein
interaction may result from an altered form of the m1 receptor in AD. The
combined use of radioligand binding and receptor-domain specific antibodies has
permitted the re-examination of the status of muscarinic receptor subtypes in the
human brain. In AD, normal levels of m1 receptor [3H]-pirenzepine binding
contrasted with diminished m1 immunoreactivity, further suggesting that there is
an altered form of the m1 receptor in the disease. Reduced m2 immunoreactivity
was consistent with decreased numbers of m2 binding sites. Increased levels of m4
receptors were observed in both binding and immunoreactivity measurements. These
findings suggest one possible explanation for the relative ineffectiveness of
cholinergic replacement therapies used to date and suggest potential new
directions for development of effective therapeutic strategies for AD.
PMID- 10188788
TI - Preclinical and phase 1 clinical characterization of CI-979/RU35926, a novel
muscarinic agonist for the treatment of Alzheimer's disease.
AB - In vitro and in vivo characterization in rodents and monkeys shows that CI
979/RU35926 is a partial muscarinic agonist with equal affinity for the five
subtypes of muscarinic receptors. It activates central cholinergic receptors as
shown by its ability to decrease body temperature, enhance local cortical blood
flow and increase cortical arousal measured by QEEG. Further, it reverses spatial
memory deficits in rats with ibotenic acid-induced lesions of forebrain
cholinergic neurons. Signs of peripheral cholinergic stimulation appear at doses
higher or equal to those necessary to produce central activity. In a single-dose
tolerance study in young, healthy human volunteers, CI-979/RU35926 was well
tolerated at doses of 0.002-1.0 mg with cholinergic symptoms such as
hypersalivation and sweating, observed at 2-4 mg. It demonstrated linear
pharmacokinetic behavior over a dose range of 0.1 to 4 mg and elimination half
life varied from 2-5 hours. Measurement of unchanged drug in urine suggests that
the drug was extensively metabolized. Thus, the safety profile supported further
clinical evaluation and CI-979/RU35926 is currently in Phase II clinical trials.
PMID- 10188789
TI - Phase I clinical trials with WAL 2014, a new muscarinic agonist for the treatment
of Alzheimer's disease.
AB - The safety, tolerability and pharmacological activity of WAL 2014, a new
centrally-acting M1 agonist were examined in two clinical studies (0.5-80 mg and
100-160 mg). Single increasing p.o. doses were administered to groups of 8
volunteers (6 verum, 2 placebo) each. Both studies were placebo controlled with
single-blind observation within the respective dose groups. Vital functions (BP,
HR, resp. rate) did not reveal any clinically significant substance-induced
changes up to a dose level of 60 mg. A slight, but obvious increase in HR was
measured with a dose of 80 mg and higher; a slight increase in systolic BP was
registered at the dose levels of 120 and 160 mg. No substance-related alterations
were observed in the laboratory tests (exception: a significant, reversible
increase of the salivary fraction of alpha-amylase in 3 volunteers at the dose
levels 100 mg-140 mg). The majority of volunteers reported an increased salivary
secretion with doses of 40 mg and higher; this was confirmed by the greater
volume of measured saliva. Furthermore, with doses of 100 mg upwards there were
isolated reports of side effects such as a desire to urinate, a burning sensation
on urination, increased lacrimation and nasal secretion, disturbances of
accommodation, heartburn, rumbling of the stomach as well as cramps, nausea,
diarrhoea, excessive sweating and palpitation. WAL 2014 did not cause any
abnormal changes in the EEG. Dose dependent central effects were observed with
40, 60, 80, 100 and 140 mg treatments. Pharmacokinetic data indicate a rapid and
good absorption and an absolute bioavailabitlity > or = 70%. The pharmacodynamic
and side effects observed in both studies are regarded as being drug-dependent
and might be due to the cholinergic activity of the compound and a weak
sympathetic activation via M1 receptors. In summary, the substance did not
produce any effects in the dose range tested to suggest further use in man might
be inadvisable.
PMID- 10188791
TI - Regulation of muscarinic receptor expression by changes in mRNA stability.
AB - Regulation of muscarinic acetylcholine receptor (mAChR) subtype mRNAs was
investigated in the human neuroblastoma cell line IMR-32 and in transfected CHO
cells. IMR-32 cells express both m1 and m3 subtypes of mAChR. Exposure of IMR-32
cells to the muscarinic agonist, carbamylcholine (CBC) leads to a time dependent
down-regulation of mAChRs which was maximal by 9 hours. mAChR activation resulted
in a differential regulation of mAChR subtype mRNAs. m1 mAChR mRNA was down
regulated following 12 hours of agonist treatment and was associated with a
decreased stability of the receptor transcript. In contrast, the m3 mAChR mRNA
was resistant to agonist treatment for up to 24 hours. Using transfected CHO
cells, we identified sequence elements within the 3'-untranslated region (3'-UTR)
of the m1 mAChR gene which dictate agonist-induced destabilization of the m1
mAChR mRNA. Removal of these sequences abolished the ability of chronic agonist
exposure to destabilize m1 mAChR mRNA. These findings suggest that sequence
specific differences between m1 and m3 mAChR subtypes, which both preferentially
couple to hydrolysis of phosphoinositides, may be responsible for differences in
the regulation of mAChR gene expression.
PMID- 10188790
TI - The role of charge interactions in muscarinic agonist binding, and receptor
response coupling.
AB - Site-directed mutagenesis has been used to evaluate the roles of the key
aspartate and arginine residues in transmembrane domain three of the muscarinic
receptors. The results suggest that the formation of an ionic bond between the
Asp carboxylate group and the onium headgroup is essential to anchor
acetylcholine in its active, bound conformation in both binary agonist-receptor
and ternary agonist-receptor-G-protein complexes, but that secondary, non
productive binding modes, promoted by non-polar forces, may contribute to binary
complex formation by other ligands. The positive charge of the arginyl side-chain
is central to the recognition, and subsequent activation of G-proteins by the
agonist-M1 mAChR complex.
PMID- 10188793
TI - Muscarinic acetylcholine receptors: structural basis of ligand binding and G
protein coupling.
AB - Muscarinic acetylcholine receptors (m1-m5) were studied by a combined molecular
genetic/pharmacologic approach to elucidate the molecular characteristics of the
ligand binding site and of the receptor domains involved in G protein coupling.
Site-directed mutagenesis studies of the rat m3 muscarinic receptor suggest that
the acetylcholine binding domain is formed by a series of hydrophilic amino acids
located in the "upper" half of transmembrane domains (TM) III, V, VI, and VII.
Moreover, we showed that mutational modification of a TM VI Asn residue (Asn507
in the rat m3 receptor sequence) which is characteristic for the muscarinic
receptor family has little effect on high-affinity acetylcholine binding and
receptor activation, but results in dramatic reductions in binding affinities for
certain subclasses of muscarinic antagonists. The N-terminal portion of the third
intracellular loop (i3) of muscarinic and other G protein-coupled receptors has
been shown to play a central role in determining the G protein coupling profile
of a given receptor subtype. Insertion mutagenesis studies with the rat m3
muscarinic receptor suggest that this region forms an amphiphilic alpha-helix and
that the hydrophobic side of this helix represents an important G protein
recognition surface. Further mutational analysis of this receptor segment showed
that Tyr254 located at the N-terminus of the i3 loop of the m3 muscarinic
receptor plays a key role in muscarinic receptor-induced Gq activation. The
studies described here, complemented by biochemical and biophysical approaches,
should eventually lead to a detailed structural model of the ligand-receptor-G
protein complex.
PMID- 10188792
TI - Kinetic and biophysical analysis of the m2 muscarinic receptor.
AB - The recombinant Pm2 muscarinic receptor expressed in Chinese hamster ovary (CHO)
cells was used as a model system to examine receptor-effector coupling and ligand
binding. In CHO cells, equilibrium binding studies and the dependence on receptor
number per cell of the maximum response and EC50 values for agonist stimulation
of phosphatidylinositol metabolism and inhibition of cAMP formation were
consistent with a modified ternary complex model of signal transduction that
included a physiologically noncompetent receptor state. Detailed kinetic studies
of oxotremorine M (Oxo-M) binding to CHO cell membranes suggested that agonist
interactions at the high affinity class of binding sites are complicated and
depend on receptor expression levels. At low levels of expression, kinetic data
were consistent with a special case of a mechanism in which Oxo-M shifts the
equilibrium between two receptor conformations while at high levels of
expression, it was necessary to evoke receptor-receptor interactions to explain
the kinetic data. Far ultraviolet circular dichroism studies of the purified
recombinant receptor showed a high content of alpha-helical secondary structure
and small changes in secondary structure upon antagonist, but not agonist,
binding.
PMID- 10188794
TI - Mutations of aspartate 103 in the Hm2 receptor and alterations in receptor
binding properties of muscarinic agonists.
AB - Aspartate 103 (D103) in the third transmembrane domain of the Hm2 receptor was
mutated to glutamate (D103E), asparagine (D103N), or alanine (D103A). As measured
by [3H]-NMS, no significant binding was observed in D103A, while a 2-fold
decrease in ligand affinity was seen in D103E and a 32-fold decrease in affinity
was found in the D103N mutant. Examination of reference agonists showed greater
loss of affinity in D103N than in D103E with the rank order of change being: L
607,207>carbachol>arecoline>pilocarpine>oxotremorine>McN-A-343. Of the novel 1
azabicyclo[2.2.1]-heptan-3-one oxime agonists examined, arylacetylene oximes
showed little alteration in binding in either the D103E or D103N mutants, while
the geometric isomers of several bicyclic aryl-ene-yne oximes showed significant
changes in affinity, especially in the D103N mutant. Thus, overall size of the
agonist and/or spatial orientation of the molecule within the binding pocket
contribute to changes measured in binding.
PMID- 10188795
TI - Diverse pre- and post-synaptic expression of m1-m4 muscarinic receptor proteins
in neurons and afferents in the rat neostriatum.
AB - We have utilized subtype specific antibodies to determine the cellular and
subcellular distributions of the muscarinic acetylcholine receptor subtypes that
are highly expressed in the rat striatum (m1-m4). Each receptor is expressed in
distinct populations of striatal neurons in the relative proportions predicted by
their mRNAs. They concentrate at post-synaptic sites and each of the four
subtypes are also transported to pre-synaptic sites. m2 appears to be the only
presynaptic autoreceptor in the striatum, but it is also localized in non
cholinergic terminals. These distinct pre- and post-synaptic localizations
suggest that muscarinic receptor subtype diversity evolved to enable increasingly
complex responses to acetylcholine release.
PMID- 10188796
TI - Molecular analysis of the regulation of muscarinic receptor expression and
function.
AB - Several systems are being used to determine the molecular and cellular basis for
the regulation of expression and function of the muscarinic receptors. Treatment
of chick heart cells in culture results in decreased levels of mRNA encoding the
cm2 and cm4 receptors. This probably results from decreased gene transcription
which requires concomitant mAChR-mediated inhibition of adenylyl cyclase and
mAChR-mediated stimulation of phospholipase C. Site-directed mutagenesis was used
to demonstrate that the single tyrosine residue in the carboxyl-terminal
cytoplasmic tail of the m2 receptor is involved in agonist-induced down
regulation but not sequestration. Activation of heterologous receptors in chick
heart cells can also regulate mAChR mRNA levels. A cAMP-regulated luciferase
reporter gene, has been used to demonstrate that the m4 receptor preferentially
couples to Gi alpha-2 or Go alpha over Gi alpha-1 or Gi alpha-3 to mediate
inhibition of adenylyl cyclase activity. Finally, in order to determine the role
of individual receptor subtypes in muscarinic-mediated responses in vivo, we are
beginning to use the method of targeted gene disruption by homologous
recombination to generate mice deficient in specific receptor subtypes.
PMID- 10188797
TI - Acetylcholine muscarinic receptor regulation of the Ras/Raf/MAP kinase pathway.
AB - Acetylcholine muscarinic m1 receptors and m2 receptors are predominantly coupled
to the heterotrimeric G proteins Gq, 11 and Gi, respectively. Stimulation of the
m1 and m2 receptors in different cell types activate the Ras/Raf/MAP kinase
pathway. The ability of the m1 receptor to activate the MAP kinase pathway is
dependent on the isoforms of adenylyl cyclase expressed in specific cell types.
Specific adenylyl cyclases respond to different signals, including calcium and
protein kinase C, with increased cAMP synthesis resulting in protein kinase A
activation. Stimulation of protein kinase A inhibits Raf and subsequent MAP
kinase activation by G protein-coupled receptors and growth factor receptor
tyrosine kinases. G protein-coupled receptors can positively and negatively
regulate the responsiveness of tyrosine kinase-stimulated response pathways.
PMID- 10188798
TI - Multiple mechanisms involving protein phosphorylation are linked to
desensitization of muscarinic receptors.
AB - Agonists induce phosphorylation of m2 muscarinic receptors (mAChR) in several
cell types. This phosphorylation correlates with desensitization. The mechanisms
underlying mAChR phosphorylation have been investigated using several in vitro
approaches. Protein kinase C phosphorylated the purified and reconstituted m2
mAChR to a stoichiometry of approximately 5 mols P/mol receptor; this
phosphorylation resulted in the decreased ability of receptors to activate G
proteins. Although the phosphorylation by PKC was not modulated by agonist
binding to the mAChR, heterotrimeric G-proteins were able to completely block the
PKC-mediated effects. If significant receptor/G-protein coupling occurs in vivo,
agonists would be required to promote dissociation of the G-proteins from the
receptors and reveal the phosphorylation sites for PKC. Members of the G-protein
coupled receptor kinase (GRK) family also phosphorylated the purified and
reconstituted m2 mAChR. In contrast to PKC, the GRKs phosphorylated the m2 mAChR
strictly in an agonist-dependent manner. GRK mediated phosphorylation perturbed
receptor/G-protein coupling. In addition, phosphorylation allowed for arrestin
binding to the m2 mAChR which should further contribute to desensitization. Using
a new strategy that does not require purification and reconstitution of receptors
for GRK studies, the m3 mAChR were revealed as substrates for the GRKs. For both
the m2 and m3 receptor subtypes, the most effective kinases were GRK 2 and 3.
Phosphorylation of the receptors by these enzymes was stimulated by low
concentrations of G-proteins and by membrane phospholipids. Thus, multiple
mechanisms involving protein phosphorylation appear to contribute to the overall
process of mAChR desensitization.
PMID- 10188799
TI - Dual modulation of a potassium channel by the m1 muscarinic and beta2-adrenergic
receptors.
AB - Neurotransmitter receptors alter membrane excitability and synaptic efficacy by
generating intracellular signals that ultimately change the properties of ion
channels. Given their critical role in controlling cell membrane potential,
potassium channels are frequently the targets of modulatory signals from many
different G protein-coupled receptors. However, due to the heterogeneity of
potassium channel expression in vivo, it has been difficult to determine the
molecular mechanisms governing the regulation of molecularly defined potassium
channels. Through expression studies in Xenopus oocytes and mammalian cells, we
found that the m1 muscarinic acetylcholine receptor (mAChR) potently suppresses a
cloned delayed rectifier potassium channel, termed RAK, through a pathway
involving phospholipase C activation and direct tyrosine phosphorylation of the
RAK protein. In contrast, we found that RAK channel activity is strongly enhanced
following agonist activation of beta2-adrenergic receptors; this effect requires
a single PKA consensus phosphorylation site located near the amino terminus of
the channel protein. These results demonstrate that a specific type of potassium
channel that is widely expressed in the mammalian brain and heart is subject to
both positive and negative regulation by G protein-dependent pathways.
PMID- 10188801
TI - Bimodal regulation of cyclic AMP by muscarinic receptors. Involvement of multiple
G proteins and different forms of adenylyl cyclase.
AB - In membranes of rat olfactory bulb, muscarinic receptor agonists stimulate basal
adenylyl cyclase activity . This response is inhibited by a number of muscarinic
receptor antagonists with a rank order of potency suggesting the involvement of
the M4 muscarinic receptor subtype. The stimulatory effect does not require Ca2+
and occurs independently of activation of phosphoinositide hydrolysis.
Pretreatment with pertussis toxin completely prevents the muscarinic stimulation
of adenylyl cyclase, indicating the participation of G proteins of the Gi/Go
family. Immunological impairment of the G protein, Gs, also reduces the
muscarinic response, whereas concomitant activation of Gs-coupled receptors by
CRH or VIP results in a synergistic stimulation of adenylyl cyclase activity.
Although these data suggest a role for Gs, a body of evidence indicates that the
muscarinic receptors do not interact directly with this G protein. Moreover, the
Ca2+/calmodulin (Ca2+/CaM)- and forskolin-stimulated enzyme activities are
inhibited by muscarinic receptor activation in a pertussis toxin-sensitive manner
and with a pharmacological profile similar to that observed for the stimulatory
response. These data indicate that in rat olfactory bulb M4 muscarinic receptors
exert a bimodal control on cyclic AMP formation through a sequence of events that
may involve activation of Gi/Go proteins, synergistic interaction with Gs and
differential modulation of Ca2+/CaM-independent and -dependent forms of adenylyl
cyclase.
PMID- 10188800
TI - Functional role of M2 muscarinic receptors in the guinea pig ileum.
AB - Muscarinic agonists elicit contraction in the standard guinea pig ileum bioassay
through activation of M3 muscarinic receptors that are also linked to
phosphoinositide hydrolysis. Surprisingly, the most abundant muscarinic receptor
in the ileum is the M2 which causes a specific inhibition of cyclic AMP
accumulation elicited by the beta-adrenergic receptor. After most of the M3
receptors are inactivated, the ileum still retains high sensitivity to muscarinic
agonists provided that the contractile responses are measured in the presence of
histamine and forskolin, which together, have no effect on contraction. Under
these conditions, the potencies of antagonists for blocking the contractile
response are consistent with those expected for an M2 response. Moreover, the
muscarinic contractile response measured in the presence of histamine and
forskolin after inactivation of M3 receptors is pertussis toxin sensitive. In
contrast, muscarinic contractions in the standard bioassay are pertussis toxin
insensitive. These results demonstrate that the M2 muscarinic receptor can cause
an indirect contraction of the guinea pig ileum by preventing the relaxing effect
of agents that increase cAMP.
PMID- 10188802
TI - Prejunctional muscarinic receptors regulating neurotransmitter release in
airways.
AB - Prejunctional pA2 values of five muscarinic antagonists were determined in the
guinea-pig trachea under stimulation conditions in which the antagonists alone
did not enhance acetylcholine release. The antagonists were partly selective at
M1 (pirenzepine), M2 (AQ-RA 741, himbacine) and M3 receptors
(hexahydrosiladifenidol, dicyclomine). The profile of the antagonist affinities
was different from that obtained at cardiac M2 receptors but resembled the
profile reported in the literature for the cloned m4 receptor. This suggests that
autoinhibition of acetylcholine release in the trachea is mediated via M4
receptors.
PMID- 10188803
TI - Multiple G-protein-coupled pathways inhibit N-type Ca channels of neurons.
AB - Muscarinic receptors depress Ca2+ currents in superior cervical ganglion neurons
by two signaling pathways. One is sensitive to pertussis toxin and acts rapidly
by a membrane-delimited pathway on the channels. The other is not sensitive to
pertussis toxin and acts more slowly through an unknown second messenger. These
pathways are shared with several other agonists.
PMID- 10188804
TI - Sixth International Symposium on Subtypes of Muscarinic Receptors. Summary and
closing comments.
PMID- 10188805
TI - The Otto Loewi New Investigator Awards for 1995.
PMID- 10188806
TI - Possible inconsistencies in study on cyclooxygenase.
PMID- 10188807
TI - Systemic and tissue chamber fluid platinum concentrations released from cis
diamminedichloroplatinum II-impregnated polymethylmethacrylate in healthy dogs.
AB - OBJECTIVES: To determine systemic and local platinum concentrations released from
subcutaneously implanted cis-diamminedichloroplatinum (cisplatin) -impregnated
polymethylmethacrylate (PMMA) and to evaluate systemic or local adverse
reactions. ANIMALS: 6 healthy dogs. PROCEDURE: Cisplatin (20 mg) was inserted
into PMMA that was fashioned into cylinders and placed into subcutaneous tissue
chambers overlying the thorax (treated site). An empty tissue chamber was placed
over the opposite side (control site). Plasma samples were obtained for platinum
determination before implantation, at 3, 6, and 12 hours after implantation on
day 0, and once daily on days 1, 2, 3, 7, 14, 21, and 29. At similar times on
similar days, tissue chamber fluid samples also were obtained for platinum
determination. Complete blood count, serum urea nitrogen and creatinine
concentration determinations, and urinalyses were performed on days 1, 2, 3, 7,
14, 21, and 29. Complete necropsy was performed at conclusion of the study.
RESULTS: Tissue chamber platinum concentrations at the treated site were
significantly greater than plasma and control site tissue chamber concentrations
on days 2, 3, 7, 10. Mean plasma platinum concentration at 3 (0.735 microg/ml), 6
(0.691 microg/ml), 12 (0.534 microg/ml), 24 (0.131 microg/ml), 48 (0.2
microg/ml), 72 (0.1 microg/ml), and 158 (0.014 microg/ml) hours was significantly
greater than pretreatment values (0.0 microg/ml). Plasma platinum concentration
10 days after treatment (0.011 microg/ml) did not significantly differ from
pretreatment values. Local or systemic adverse reactions were not apparent.
CONCLUSIONS: The route of cisplatin administration was safe. Greater
concentration of platinum was released locally relative to plasma concentration
for an extended period.
PMID- 10188808
TI - Evaluation of temporal and spatial clustering of horses with Corynebacterium
pseudotuberculosis infection.
AB - OBJECTIVE: To determine whether horses with Corynebacterium pseudotuberculosis
infections that were examined at a veterinary medical teaching hospital between
July 1, 1992, and June 30, 1994 had patterns of temporal or spatial clustering.
ANIMALS: 134 case and 800 control horses randomly selected from all non-case
horses admitted during the study period. PROCEDURES: Admission date and
geographic location were determined. Scan, Cuzick & Edwards', and Knox tests were
applied to determine whether case horses had patterns of temporal or spatial
clustering. RESULTS: For all windows > or = 3 days (134 case horses) and > or = 7
days (subset of 69 case horses), results of the Scan test were significant.
Results of Cuzick & Edwards' test were significant for all data sets. A
significant spatial cluster of case horses was observed for October, November,
and December 1992. Results of the Knox test were significant for temporal
intervals between 7 and 56 days and spatial intervals between 4.3 and 6.5 km.
Higher Knox(x) proportions were observed for temporal intervals of 0 to 7, 8 to
14, 22 to 28, and 29 to 35 days. CONCLUSIONS: Significant spatial and temporal
clustering of horses with C pseudotuberculosis infection was detected. CLINICAL
RELEVANCE: Analysis of the results strongly indicates that this disease is
directly or indirectly (ie, short distance and time) transmitted. In addition,
data analyses indicated an incubation period of 3 to 4 weeks. The disease could
be transmitted through horse-to-horse contact or from infected to susceptible
horses via insects, other vectors, or contaminated soil.
PMID- 10188809
TI - Breakage and deformation characteristics of hypodermic devices under static and
dynamic loading.
AB - OBJECTIVE: To characterize the strength and limitations of hypodermic needles to
reduce the risk of leaving broken needles in the flesh of animals. SAMPLE
POPULATION: Skin of porcine cadavers. Procedure-Stainless steel needles of
various gauges combined with aluminum and plastic hubs were subjected to standard
test-stand conditions to compare strength under various loading regimens. A
device that simulated animal motion was constructed to test breakage
characteristics during animal movement. RESULTS: Needles and needle/hub
assemblies were resilient to needle breakage, except when bent needles were
straightened and a load reapplied. Needle gauge and length drastically affected
strength. For 16-and 20-gauge needles, a 1.0-in needle was 1.6 times stronger
than a 1.5-in needle. Adding animal movement for 20-gauge, 1.5-in needles
resulted in a 40% increase in hub failures for plastic, compared to aluminum hub
needles. CONCLUSIONS AND CLINICAL RELEVANCE: Findings of this study are important
considerations for meat packers to address in their Hazard Analysis and Critical
Control Points plans.
PMID- 10188810
TI - Evaluation of washing with cold water to facilitate heat dissipation in horses
exercised in hot, humid conditions.
AB - OBJECTIVE: To determine whether body temperature of horses exercised in hot,
humid conditions and then repetitively washed with cold water will decrease more
rapidly than that of horses that are not washed, and to determine whether washing
with cold water has deleterious effects on horses. ANIMALS: 5 physically fit
Thoroughbred mares, 3 to 10 years old. PROCEDURES: Horses were exercised on a
high-speed treadmill in hot (31.1+/-0.3 C), humid (relative humidity, 77.7+/-2%)
conditions. Exercise was terminated when pulmonary artery temperature reached
41.5 C. Values for pulmonary artery, rectal, and left gluteal muscle temperatures
were compared throughout a 30-minute recovery period after exercise during which
horses stood quietly (passive cooling) or were cooled (active cooling) by
repeated applications of cold (1 5.6+/-0.6 C) water. RESULTS: Pulmonary artery
temperature was significantly less for actively cooled horses, compared with
passively cooled horses 4 minutes into the recovery period. Left gluteal muscle
temperature decreased significantly in actively cooled, but not passively cooled,
horses during the recovery period. Heart rate and rectal temperature were
significantly less for actively cooled horses by 15 minutes of the recovery
period. Cooling technique did not effect hydration status, muscle health, or
serum electrolyte concentrations. Active cooling did not cause obvious adverse
effects. CONCLUSION AND CLINICAL RELEVANCE: Active cooling by washing with cold
water is a safe, effective means for facilitating heat dissipation of horses
after exercise in a hot, humid environment.
PMID- 10188811
TI - Measurement of synovial fluid and serum concentrations of the 846 epitope of
chondroitin sulfate and of carboxy propeptides of type II procollagen for
diagnosis of osteochondral fragmentation in horses.
AB - OBJECTIVE: To determine whether serum or synovial fluid concentrations of
chondroitin sulfate epitope 846 and carboxy propeptides of type II collagen
(CPII) can be used to diagnose osteochondral fragmentation (OC) in horses.
ANIMALS: 38 horses with unilateral OC of the radiocarpal (n = 31) or intercarpal
(33) joints and 8 clinically and radiographically normal horses. Procedures-For
horses with OC, serum and synovial fluid concentrations of epitope 846, CPII, and
keratan sulfate (KS) were determined, along with synovial fluid WBC counts and
total protein concentrations. Serum epitope 846, CPII, and KS concentrations were
measured in control horses. RESULTS: Synovial fluid epitope 846 and total protein
concentrations were significantly higher in the joints with OC than in unaffected
joints, but CPII and KS concentrations and WBC counts were not. Synovial fluid
total protein and 846 epitope concentrations were linearly related to grade of
OC. Serum epitope 846 and CPII concentrations were significantly higher in horses
with OC than in control horses. Discriminant analysis allowed 27 of 34 (79%)
horses to be correctly classified as having or not having OC on the basis of
serum epitope 846 and CPII concentrations. CONCLUSIONS: Results suggest that
serum and synovial fluid concentrations of epitope 846 and CPII are associated
with OC. Increases in concentrations of epitope 846 and CPII suggest that
increased synthesis of cartilage aggrecan and type II procollagen may be
associated with OC. CLINICAL RELEVANCE: Measurement of serum epitope 846 and CPII
concentrations may be useful in the diagnosis of OC in horses.
PMID- 10188812
TI - Granuloma development in cattle after intratonsilar inoculation with
Mycobacterium bovis.
AB - OBJECTIVE: To examine the temporal development of tuberculous lesions in cattle
inoculated with Mycobacterium bovis. ANIMALS: 15 mature crossbred cows obtained
from a herd with no history of M bovis infection. PROCEDURE: Inoculation of
cattle was done by intratonsilar instillation of 1.48 X 10(5) to 5.4 X 10(7)
colony-forming units of M bovis strain 2045T. At 3 to 4 hours, 4 weeks, 6 weeks,
and 8 weeks after inoculation, tissues were examined for gross and microscopic
lesions and processed for isolation of M bovis. RESULTS: Retropharyngeal lymph
nodes from cattle examined 4 weeks after inoculation contained microgranulomas
consisting of aggregates of macrophages with few neutrophils. Retropharyngeal
lymph nodes from all cattle examined 6 and 8 weeks after inoculation contained
multiple, large, coalescing granulomas consisting of central areas of necrosis
with mild fibrosis, numerous macrophages, lymphocytes, plasma cells,
multinucleated giant cells, and neutrophils. Three of 8 cattle examined 6 or 8
weeks after inoculation had lesions in nonretropharyngeal sites with morphologic
characteristics similar to that seen in retropharyngeal lymph node granulomas
from cattle examined 4 weeks after inoculation. CONCLUSION: Granulomas can
develop in draining lymph nodes of cattle in as little as 4 weeks after
inoculation via intratonsilar instillation of M bovis. Intralesional morphologic
changes between 4 and 6 weeks after inoculation indicate an increase in cellular
chemotaxis and differentiation. Dissemination of bacteria to distant sites most
likely was by lymphatic and hematogenous routes after establishment of the
primary infection in retropharyngeal lymph nodes.
PMID- 10188813
TI - Evaluation of activity of selected ophthalmic antimicrobial agents in combination
against common ocular microorganisms.
AB - OBJECTIVE: To determine in vitro efficacy of gentamicin, tobramycin, and
miconazole when used in combination, with or without atropine, against
Pseudomonas or Aspergillus sp. PROCEDURE: Selected ophthalmic agents were
combined for predetermined times. Sterile disks impregnated with the combined
solutions were prepared and placed on Mueller-Hinton plates that were seeded with
Pseudomonas or Aspergillus sp. Zones of growth inhibition were measured at
postincubation hours 24 and 48. RESULTS: Tobramycin alone inhibited growth of
Pseudomonas sp, whereas miconazole inhibited growth of Aspergillus sp.
Significant differences in zones of growth inhibition when atropine was combined
with tobramycin, when gentamicin was combined with miconazole, or when atropine
was combined with miconazole and gentamicin, were not detected. CLINICAL
RELEVANCE: Combining selected ophthalmic therapeutic agents for as long as 6
hours does not appear to alter the in vitro efficacy of the agents against
microorganisms used in this study.
PMID- 10188814
TI - Effect of dietary n-6-to-n-3 fatty acid ratio on complete blood and total white
blood cell counts, and T-cell subpopulations in aged dogs.
AB - OBJECTIVE: To determine effect of diets with variable n-6-to-n-3 fatty acid (FA)
ratio on CD4+ and CD8+ T-lymphocyte subpopulations, and on results of routine
laboratory analyses (CBC and total WBC count, serum biochemical analyses, and
urinalysis). ANIMALS: 20 healthy, aged (9.5 to 11.5 years old) female Beagles.
PROCEDURE: Dogs were fed 1 of 3 diets that contained 6% fat by weight but
differed in amounts of n-6 and n-3 FA. For 11 weeks, 6 dogs were fed a low
concentration of n-3 FA (ratio, 31:1), 7 were fed a medium concentration (5.4:1),
and 7 were fed a high concentration (1.4:1). Preprandial blood and urine samples
were collected before beginning the study and at 8 weeks for evaluation of
laboratory variables. Before and at 3, 6, and 8 weeks during the study, blood was
drawn for total WBC and lymphocyte counts and for characterization of T-cell
subpopulations. At 8 and 10 weeks, dogs were vaccinated with keyhole limpet
hemocyanin suspension. Blood was drawn 4 days after each vaccination, and
lymphocytes were isolated for flow cytometry. Effects of diet and vaccination on
each variable were determined. RESULTS: After vaccination, total lymphocyte count
increased and CD4+ T lymphocyte count and the CD4(+)-to-CD8+ ratio decreased in
dogs consuming the diet with n-6-to-n-3 FA ratio of 1.4:1. CONCLUSION: Feeding a
diet with n-6-to-n-3 FA ratio of 1.4:1 had significant effects on CD4+ T
lymphocytes in healthy, aged Beagles after vaccination.
PMID- 10188815
TI - Effects of dietary cysteine on blood sulfur amino acid, glutathione, and
malondialdehyde concentrations in cats.
AB - OBJECTIVE: To determine effects of dietary cysteine on blood sulfur amino acids
(SAA), reduced glutathione (GSH), oxidized glutathione (GSSG), and
malondialdehyde (MDA) concentrations in cats. ANIMALS: 12 healthy adult cats.
PROCEDURE: Cats were fed diets with a nominal (0.50 g/100 g dry matter [DM]),
moderate (1.00 g/100 g DM), or high (1.50 g/100 g DM) cysteine content in a 3 X 3
Latin square design with blocks of 8 weeks' duration. Venous blood samples were
collected after each diet had been fed for 4 and 8 weeks, and a CBC and serum
biochemical analyses were performed; poikilocyte, reticulocyte, and Heinz body
counts were determined; and MDA, GSH, GSSG, and SAA concentrations were measured.
RESULTS: Blood cysteine and MDA concentrations were not significantly affected by
dietary cysteine content. Blood methionine, homocysteine, and GSSG concentrations
were significantly increased when cats consumed the high cysteine content diet
but not when they consumed the moderate cysteine content diet, compared with
concentrations obtained when cats consumed the nominal cysteine content diet.
Blood GSH concentrations were significantly increased when cats consumed the
moderate or high cysteine content diet. CONCLUSIONS: Increased dietary cysteine
content promotes higher blood methionine, homocysteine, GSH, and GSSG
concentrations in healthy cats. CLINICAL RELEVANCE: Supplemental dietary cysteine
may be indicated to promote glutathione synthesis and ameliorate adverse effects
of oxidative damage induced by disease or drugs.
PMID- 10188816
TI - Identification and clinical assessment of suspected vaccine-related field strains
of porcine reproductive and respiratory syndrome virus.
AB - OBJECTIVE: To determine the origin and clinical relevance of selected strains of
porcine reproductive and respiratory syndrome (PRRS) virus (PRRSV). ANIMALS: 38
pigs without antibodies for PRRSV. PROCEDURE: A seemingly uncommon restriction
endonuclease digestion site in a commercially available vaccine strain of
attenuated PRRSV was tested for its stability and prevalence under defined
conditions. Selected field strains of PRRSV, with or without the restriction-site
marker, were subsequently tested in pigs for virulence and for their ability to
replicate competitively in pigs simultaneously given the vaccine. RESULTS: Under
experimental conditions, the restriction-site marker was stable during long-term
infection of pigs. It was not detected in any of the 25 field strains of PRRSV
that were isolated before use of the vaccine or 21 of 25 field strains that were
isolated after use of the vaccine but that, on the basis of previous testing,
were believed unrelated to the vaccine strain. Conversely, it was detected in 24
of 25 field strains that were isolated after use of the vaccine and that, on the
basis of previous testing, were believed to be direct-line descendants of the
vaccine strain. Putative vaccine-related strains caused more pronounced
pathologic changes than did the vaccine strain alone, and they predominated
during replication in pigs also given the vaccine strain. CONCLUSIONS: In some
swine herds, the vaccine strain may have persisted and mutated to a less
attenuated form. CLINICAL RELEVANCE: The potential for persistence and mutation
of specific strains of virus should be an important consideration when designing
vaccination programs involving attenuated PRRSV.
PMID- 10188817
TI - Influence of site and age on biochemical characteristics of the collagen network
of equine articular cartilage.
AB - OBJECTIVE: To determine variations in biochemical characteristics of equine
articular cartilage in relation to age and the degree of predisposition for
osteochondral disease at a specific site. SAMPLE POPULATION: Articular cartilage
specimens from 53 horses 4 to 30 years old. PROCEDURE: Healthy specimens were
obtained from 2 locations on the proximal articular surface of the first phalanx
that had different disease prevalences (site 1 at the mediodorsal margin and site
2 at the center of the medial cavity). Water, total collagen, and hydroxylysine
contents and enzymatic (hydroxylysylpyridinoline [HP]) and nonenzymatic
(pentosidine) crosslinking were determined at both sites. Differences between
sites were analyzed by ANOVA (factors, site, and age), and age correlation was
tested by Pearson's product-moment correlation analysis. Significance was set at
P< 0.01. RESULTS: Correlation with age was not found for water, collagen,
hydroxylysine contents, and enzymatic cross-linking. Nonenzymatic crosslinking
was higher in older horses and was linearly related to age (r = 0.94). Water and
collagen contents and HP and pentosidine crosslinks were significantly higher at
site 1. Hydroxylysine content was significantly lower at site 1. CONCLUSIONS:
Except for nonenzymatic glycation, the composition of articular cartilage
collagen does not change significantly in adult horses. A significant topographic
variation exists in biochemical characteristics of the articular cartilage
collagen network in equine metacarpophalangeal joints. These differences may
influence local biomechanical properties and, hence, susceptibility to
osteochondral disease, as will greater pentosidine crosslinks in older horses
that are likely to cause stiffer and more brittle cartilage.
PMID- 10188818
TI - Flow cytometric analysis of canine colonic mucosal lymphocytes from
endoscopically obtained biopsy specimens.
AB - OBJECTIVE: To validate use of canine colonic biopsy specimens obtained via
endoscopy as a source of mucosal lymphocytes (ML) for flow cytometric analysis.
SAMPLE POPULATION: Mucosal biopsy specimens from 10 adult dogs. PROCEDURE:
Mucosal lymphocyte subsets obtained from excised colon were compared with ML
subsets obtained from biopsy specimens obtained by use of an endoscopic forceps
(6 dogs). Endoscopic colonic biopsy specimens from 4 other dogs were used to
define whether obtained ML were predominantly of intraepithelial or lamina
propria origin. Mucosal lymphocytes were isolated and labeled, using commercially
available monoclonal antibodies directed against canine cell surface antigens.
Lymphocyte subsets (cytotoxic or helper T cells; B cells) were determined by use
of flow cytometric analysis. RESULTS: A large number of viable ML was obtained
after dissociation of the colonic epithelium from excised colon (45.5 + 21.5 X
10(6)) and endoscopic (7.2+/-3.4 X 10(6)) biopsy specimens. Lymphocyte subsets
obtained with both methods were identical for each dog and consisted
predominantly of intraepithelial lymphocytes, with some lymphocytes from the
lamina propria. Collagenase digestion of excised colon also yielded a large
number of viable lymphocytes from the lamina propria (56.7+/-20.4 X 10(6)), but
collagenase digestion of endoscopic biopsy specimens was less rewarding.
CONCLUSION AND CLINICAL RELEVANCE: A representative sample of viable
intraepithelial ML is obtainable from endoscopic biopsy specimens. Flow
cytometric analysis, a minimally invasive technique, can be used to study ML of
client-owned animals.
PMID- 10188819
TI - Influence of fermentable fiber on small intestinal dimensions and transport of
glucose and proline in dogs.
AB - OBJECTIVE: To determine whether intestinal dimensions and nutrient absorption are
influenced by different types of dietary fiber. ANIMALS: 10 adult Beagles of both
sexes. PROCEDURE: Dogs were randomly assigned to 2 groups and fed a diet with
fermentable fibers (beet pulp and oligofructose) or a nonfermentable fiber
(cellulose) for 6 weeks. Effects of the diets on small intestinal dimensions were
measured, and transport rates for glucose and proline were determined. Kinetics
of glucose and proline uptake were defined in the proximal and middle regions of
the small intestine, respectively. RESULTS: Small intestines of dogs fed
fermentable fiber had 28% more nominal surface area and 37% more mucosal mass,
were 35% heavier, and had 95% higher capacity for carrier-mediated glucose uptake
than those of dogs fed a diet with cellulose. Differences were more pronounced in
the proximal portion of the intestine. CONCLUSIONS AND CLINICAL RELEVANCE: Diets
containing fermentable fibers increase small intestinal dimensions and the
capacity for nutrient absorption in dogs. These changes may reduce the risk of
enteric infections or aid in treatment of intestinal diseases, particularly those
involving reduced nutrient absorption.
PMID- 10188820
TI - Effects of sample storage and delayed secondary enrichment on detection of
Salmonella spp in swine feces.
AB - OBJECTIVE: To determine effects of fecal sample storage and delayed secondary
enrichment (DSE) on detection of Salmonella spp in swine feces. Sample Population
Fecal samples obtained from 84 pigs in a commercial herd. PROCEDURE: Each fecal
sample underwent 3 storage treatments: no storage (ie, processed on the day of
collection), storage at 4 C for 6 days, and storage at -15 C for 14 days. After
assigned storage treatments, all samples were enriched in Rappaport-Vassiladias
(RV) broth (single enrichment) and plated on XLT4 agar. Delayed secondary
enrichment was performed, using single enrichment broths that were stored for 4
days at room temperature. RESULTS: Of 504 cultures, 186 (36.9%) were Salmonella
positive. A difference in proportions of samples with positive results was not
found between same-day processing and storage at 4 C for 6 days. Compared with
use of single enrichment for 24 hours (34% positive), use of DSE resulted in a
greater proportion (40%; P < 0.001) of samples with positive results. Estimated
relative sensitivities for the storage methods were 0.90, 0.85, and 0.71 for same
day processing, storage at 4 C for 6 days, and storage at -15 C for 14 days,
respectively. CONCLUSIONS: Where practical, processing of fecal samples on the
day of collection is recommended, although storage at 4 C for several days does
not result in marked loss of sensitivity. Improved detection associated with DSE
warrants further investigation and optimization.
PMID- 10188821
TI - Effects of bovine serum albumin on function of cryopreserved stallion spermatozoa
during medium culture and uterine tube epithelial cell coculture.
AB - OBJECTIVE: To compare function of cultured cryopreserved stallion spermatozoa in
a modified Tyrode's medium (TM), with or without bovine serum albumin (BSA), or
in uterine tube (oviduct) epithelial cell (OEC) coculture in TM, with or without
BSA. SAMPLE POPULATION: Cryopreserved spermatozoa from 6 proven stallions and OEC
from bovine reproductive tracts in follicular phase. PROCEDURE: Thawed
spermatozoa were cultured in TM, with or without BSA, or cocultured with OEC
monolayers in TM, with or without BSA. Percentages of capacitated and acrosome
reacted spermatozoa were measured at 5 hours for TM cultures. Spermatozoal
survival and motility characteristics were observed over time for all culture
methods. Number of spermatozoa attaching to OEC were compared for cocultures.
RESULTS: Use of TM without BSA altered spermatozoal function in cell-free medium
culture and OEC coculture. A higher percentage of spermatozoa were acrosome
reacted in TM with BSA, although percentages of capacitated spermatozoa did not
differ. Spermatozoa survived longer and maintained superior motion in TM culture
without BSA and in OEC cocultures. More spermatozoa were able to attach to OEC in
TM without BSA. CONCLUSIONS: Incubation of cryopreserved spermatozoa in media
with BSA resulted in rapid decrease in percentage of intact, motile spermatozoa
and limited their ability to interact with OEC. CLINICAL RELEVANCE: Current
culture media used for assisted reproduction techniques in horses do not provide
functionally capacitated spermatozoa. Removal of BSA from such media improves
spermatozoal quality and survival.
PMID- 10188822
TI - Purification and biochemical characterization of equine pulmonary surfactant
protein D.
AB - OBJECTIVE: To characterize surfactant protein D (SP-D) isolated from
bronchoalveolar lavage fluid (BALF) of healthy horses. SAMPLE POPULATION: BALF
from 10 Thoroughbreds (5 males, 5 females; 26 to 40 months old) without history
or clinical signs of respiratory tract disease. PROCEDURE: BALF was obtained and
centrifuged at 33,000 X g. The supernatant was applied to a mannose-Sepharose 6B
affinity column in the presence of calcium, and the bound protein fraction was
analyzed by use of sodium dodecyl sulfate-polyacrylamide gel electrophoresis,
immunoblot analysis; amino acid composition was determined and partial sequencing
was done. Phospholipid binding and liposome aggregation assay were performed,
using purified proteins. RESULTS: The protein isolated by use of mannose affinity
matrices was SP-D. It bound carbohydrates and phosphatidylinositol, which are the
characteristic features of SP-D isolated from other animal species. Amino acid
analysis and partial primary sequence of the isolated protein indicated high
homology with rat and human SP-D. Furthermore, immunoblot analysis indicated that
equine SP-D reacted with human and rat SP-D-specific antibodies. CONCLUSION AND
CLINICAL RELEVANCE: SP-D exists in equine lungs; its measurement may be useful in
evaluating equine lung disease.
PMID- 10188824
TI - Rat and mouse organ transplantation. Introduction.
PMID- 10188823
TI - New form of X-linked dominant hereditary nephritis in dogs.
AB - OBJECTIVE: To determine features of a new form of hereditary nephritis (HN) in
dogs. ANIMALS: Parents and 16 first-generation offspring (8 males, 8 females).
PROCEDURE: Adolescent dogs that developed renal failure were euthanatized and
necropsied. Unaffected dogs were monitored until they were at least 2 years old.
Studies included light and electron microscopy of kidneys obtained from affected
and unaffected dogs and immunolabeling for collagen-IV chains in renal and
epidermal basement membranes (BM). The nucleotide sequence of a portion of exon
35 of the COL4A5 gene was determined in genomic DNA isolated from affected and
unaffected males. RESULTS: 7 of 8 male and 2 of 8 female offspring had
proteinuria and juvenile-onset chronic renal failure, which progressed more
rapidly in the males. Labeling for alpha3-alpha6(IV) chains was completely absent
in renal BM of affected males and segmentally absent in affected females.
Expression of alpha1-alpha2(IV) chains in glomerular BM (GBM) of affected dogs
was increased. Labeling for alpha5-alpha6(IV) chains in epidermal BM was absent
in affected males and segmental in affected females. Ultrastructural changes
characteristic of HN were observed in GBM of affected dogs. The sequence of exon
35 of COL4A5 was normal in affected dogs. CONCLUSIONS: This renal disease is an
example of X-linked dominant HN, with typical abnormalities of GBM ultrastructure
and alpha(IV) chain expression. CLINICAL RELEVANCE AND IMPLICATIONS FOR HUMAN
MEDICINE: Dogs with this naturally acquired progressive renal disease can be used
to investigate the pathogenesis and treatment of similar disorders in human
beings and dogs.
PMID- 10188825
TI - Organ transplantation in mice: current status and future prospects.
AB - With the development of microsurgery and molecular biology in the 1990s, the
mouse model for organ transplants has become increasingly popular. In the past 10
years, the number of studies using the mouse model has increased three-fold. All
the organ transplants, originally done in the rat model, can now be performed in
mice with high success rates. This article reviews the development, advantages,
limitations, and unique immunology of the mouse model as well as future
prospects.
PMID- 10188826
TI - Surgical technique for vascularized thymus transplantation in mice.
AB - Traditionally, mouse nonvascularized thymus implants have been used to
investigate various aspects of thymus function. However, these grafts are easily
damaged by ischemia and fail to reproduce the normal anatomy of the thymus. In
addition, the function of these grafts has not been fully examined. We have
recently developed a vascularized thymus transplant model in mice. The donor
operation consists of isolating the right lobe of the thymus and creating a
single vascular pathway. In the recipient surgery, end-to-side anastomoses
between donor brachycephalic artery and recipient right common carotid artery,
and between donor superior caval vein and recipient right external jugular vein,
were performed. We performed 10 consecutive isografts in BALB/c mice with a
success rate of 90%. The thymus grafts had a normal histology and function. This
study illustrates that it is technically possible to transplant a mouse vascular
thymus graft. This model has several advantages that make it a useful tool to
study many aspects of thymus function. We plan to use this model further to study
the potential for induction of tolerance by thymus grafts.
PMID- 10188827
TI - Model of mouse pancreaticoduodenal transplantation.
AB - Our technical procedure for mouse pancreaticoduodenal transplantation is
described. A number of methods were attempted. Among them, a modification of S.
Lee's method was thought to be the most successful procedure, which was performed
with end-to-side anastomosis of the donor portal vein to the inferior vena cava
and that of the donor aortic patch to the aorta. Even with this method, however,
arterial thrombosis or venous stenosis of the anastomoses was inevitable without
the use of some devices as well as special skills in microsurgery.
PMID- 10188828
TI - Mouse-to-rat testicle transplantation.
AB - This report details mouse-to-rat testicular transplantation with immediate
revascularization. Donor preparation involved grafting a long segment of aorta
and inferior vena cava (IVC) containing the testicular artery and vein. The graft
aorta and IVC were anastomosed to the rat aorta and IVC, respectively.
Vasovasostomy was completed and the scrotal epithelia were anastomosed to draw
the graft toward the host scrotal sac. Twenty-nine of 53 transplants were
determined to be viable. Histologically, 6- to 18-hr-old grafts displayed
moderate to minimal polymorphonuclear neutrophil (PMN) infiltrates. Ischemia set
in somewhere between 18-24 hr postoperatively. Beyond 24 hr the grafts displayed
progressive infiltration of PMN and perivascular and intertubular lymphocytes,
disorganization of the germinal epithelium, and cessation of spermatogenesis.
PMID- 10188829
TI - Review of significant microvascular surgical breakthroughs involving the heart
and lungs in rats.
AB - Models of transplantation of the heart and lung in the rat have been important in
determining the mechanisms of rejection and their treatment. Reviewed here are
several important milestones contributing to the current state of the art of
clinical heart and lung transplantation.
PMID- 10188830
TI - Long-term fate of heterotopic liver transplants in rats with portal vein inflow
only.
AB - Previous studies have suggested that hepatic arterial flow in heterotopic partial
liver transplants is necessary to ensure graft survival and regenerative
capacity. This report presents findings in a syngeneic rat strain (Lewis) that
partial liver transplants can be successfully heterotopically transplanted in the
long term with the only inflow coming from the portal vein. When the host liver
undergoes a nearly complete resection at 3-4 weeks, the transplanted liver
regenerates to maintain the health of the host. Moderate to massive
hepatocellular necrosis occurs in the first 3 months postoperatively, with
recovery by 4-5 months. Liver transplants 8-10 months postoperatively appear
architecturally normal. No host liver tissues were found to be regenerating after
subtotal host liver resection. We conclude that portal vein reconstruction
without hepatic arterial inflow can sustain a partial liver transplant in the
long term, replacing the function of the host liver.
PMID- 10188831
TI - Update on sequential isologous rat organ transplantation: pancreaticoduodenal and
kidney transplantations.
AB - This periodic report includes intermittent results of consecutive
pancreaticoduodenal (Pd) and kidney (Kt) transplants in inbred rats and results
on double kidney transplants that did not follow sequential transplant protocol.
Eight 24-month-old Lewis pancreas, kidney, and aorta served histological controls
showing normal histological architecture with no atherosclerosis developed in the
aorta. Thirty-four month old pancreas and thirty-two month old kidneys, which
resided in young hosts for at least three occasions, appeared as youthful Pd and
Kt grafts. They show normal histological appearance for more than the expected
life span of a Lewis rat. The fact that not only pancreases but also kidneys
outlived their host leads to the study of other different organs' viability as
aged valuable grafts. Nevertheless, the threats by the development of
atherosclerosis in graft-associated aortas resulted in slow progression of the
follow-ups.
PMID- 10188832
TI - Noninvasive videomicroscopic monitoring of rat small-bowel rejection.
AB - Successful small-bowel transplantation requires an early diagnosis of graft
rejection. To date, little is known about macroscopic mucosal alterations during
rejection. In the present study, these changes were analyzed in detail.
Videomicroscopic monitoring of an enterostoma was performed after allogeneic
heterotopic small-bowel transplantation in the rat (BN to LEW). Up to
postoperative day (POD) 3 a mucosal edema was noticed (stage I of
videomicroscopical alterations). The earliest changes related to rejection
appeared on POD 6. The mucosa of the grafted intestine developed patchy paleness
and interruptions in mucosal architecture. Crypts were slightly widened and their
color turned to dark red (stage IIa). Progressively, these alterations spread
over the mucosa on POD 7 (stage IIb). On POD 9, the mucosa appeared pale, villi
were shortened, and crypts appeared wide and rounded. The mucosal surface was
coated with fibrinous membranes (stage III). The videomicroscopic findings were
closely related to the histological grading of rejection. We regard this
technique of mucosal monitoring a simple and noninvasive method of detecting
allograft rejection.
PMID- 10188833
TI - One-stage total hepatectomy in the rat using microvascular anastomoses.
AB - A method is described for one-stage total hepatectomy in the rat using
microvascular techniques. The operation consists of creation of a side-to-side
mesocaval shunt performed just distal to the renal veins, total removal of the
liver with ligation of the portal vein, hepatic arteries, and the bile duct. The
vena cava is reconstructed with a segment of vena cava taken from a donor animal.
The procedure takes 32 +/- 5 min to complete. Blood glucose concentration was
maintained by infusions of balanced salt solution containing from 0.625% to 2.5%
dextrose. Mean survival time was 10.5 hr (range, 5.5 to 21.5 hr).
PMID- 10188834
TI - Immunosuppressive effect of combination schedules of brequinar with leflunomide
or tacrolimus on rat cardiac allotransplantation.
AB - Drug toxicity is one of the major problems in clinical immunosuppression.
Combining two immunosuppressants in low or ineffective doses is an attractive
strategy if it helps to reduce drug-related toxicity. We examined the
immunosuppressive efficacy of brequinar (BQR) in combination with leflunomide
(Lef) or tacrolimus (FK) in a heterotopic rat cardiac allotransplantation model.
Abdominal heterotopic heart grafts (DA x LEW) were immunosuppressed from the time
of transplantation and continued until the ninth posttransplant day (POD) in
experiments examining prophylaxis of rejection treatment (PRT). In a separate
series of experiments designed to test rescue treatment (RT), immunosuppression
was begun on POD 4 and continued for 10 days; transplanted rats were sacrificed
the following day intentionally. Cardiac rejection was monitored by palpation and
documented by light microscopy. Immunosuppressive drugs (BQR 3 mg/kg and 12
mg/kg; BQR 3 mg/kg + Lef 5 mg/kg; BQR 3 mg/kg + FK 0.5 mg/kg) were given orally
by gavage; thrice weekly according to the monotherapy or dual-therapy dosing
protocol. Median survival time of the cardiac graft for controls (no treatment)
was 5 days. BQR monotherapy 3 mg/kg (low dose) improved graft survival (P =
0.003); graft histology showed moderate acute rejection. BQR monotherapy 12 mg/kg
(therapeutic dose) application in the PRT or RT treatment arms of the study
design resulted in aortic-graft ruptures and clinical toxicity in each treatment
arm due to overimmunosuppression; normal graft morphology was maintained.
Successful rescue of rejecting grafts was histologically documented. Combining
BQR with Lef or FK in the PRT protocol showed prolonged graft survival in both
drug combination groups (median survival time, 14 days; P = 0.009 and 0.014,
respectively). Using an identical combination protocol for RT, all grafts
achieved a 14-day graft survival; cardiac histology showed reversible moderate
acute rejection. BQR given in the presence of Lef or FK not only prevented acute
rejection but intercepted it so long as it was administered; grafts were rejected
within 4 days of stopping immunosuppression in the PRT study. These combinations
using low or subtherapeutic doses may be important for controlling transplant
rejection and rescuing ongoing graft rejection. The need for continuing treatment
in this strongly allogeneic model is highlighted.
PMID- 10188835
TI - Supplement of liver enzyme by intestinal and kidney transplants in congenitally
enzyme-deficient rat.
AB - Gunn rats have a congenital deficiency of bilirubin-uridine diphosphate
glucuronyltransferase (B-UDP-GT) activity and are unable to glucuronidate
bilirubin in the bile, resulting in unconjugated hyperbilirubinemia. Other than
the liver, several organs, including small bowel and kidneys, are known to have B
UDP-GT activity in normal rats. We performed total- or partial-small-bowel
transplantation as well as kidney transplantation for Gunn rats in congenic
combination and compared the effects of these procedures. Serum total bilirubin
(TBil) levels significantly decreased from 7.84 +/- 0.24 mg/dl to 2.19 +/- 0.43
mg/dl 2 weeks after total-small-bowel transplantation (n = 12). Correlation of
hyperbilirubinemia was roughly proportional to the length of the transplanted
small bowel. There were no difference in metabolic correction between jejunal and
ileal transplantation. Serum TBil levels significantly decreased from 7.83 +/-
0.21 mg/dl to 2.24 +/- 0.98 mg/dl 2 weeks after kidney transplantation (n = 5).
In conclusion, small-bowel and kidney transplantation were effective in
correcting metabolic abnormality in Gunn rats for the period of 4-6 months.
Estimated total B-UDP-GT activity supplemented by small-bowel or kidney
transplantation was about 1/5-1/4 of the minimal requirement for the complete
normalization of serum total bilirubin levels.
PMID- 10188836
TI - Technical experiences with a microsurgical model of lymphatic reconstruction
after intestinal transplantation in rats.
AB - The surgical procedure of intestinal transplantation disrupts the graft's
lymphatic drainage. Despite morphological regeneration, the functional impairment
of the lymphatic system may contribute to many pathophysiological changes after
transplant. We describe the technical details and results of a microsurgical
model of lymphatic reconstruction (LR), which immediately reconstitutes lymphatic
drainage of the intestinal graft in rats. A total of 42 orthotopic intestinal
transplants with LR was performed. The patency of the LR was assessed between
postoperative days 2 and 100 using either methylene-blue staining of the
lymphatic vessels or mesenteric lymphoradiography. A total patency rate of 88%
was achieved. Genetic background, occurrence of rejection, and immunosuppressive
treatment with cyclosporine did not affect the patency rate. Technical aspects
and potential applications of this model are discussed.
PMID- 10188837
TI - Incipient intraepidermal cutaneous squamous cell carcinoma: a proposal for
reclassifying and grading solar (actinic) keratoses.
AB - Actinic keratoses (AKs) are primarily induced by ultraviolet (UV) radiation and
are often identified as premalignant lesions. In our opinion, AKs are
proliferations of transformed, neoplastic keratinocytes confined to the epidermis
that may eventually extend into the dermis, at which point they are termed
squamous cell carcinoma (SCC). In contrast to AKs, SCCs have the potential to
metastasize and kill. This process is analogous to that of evolving carcinoma of
the uterine cervix that has been termed cervical intraepithelial neoplasia (CIN),
a time-tested and reliable classification that provides clinicians with accurate
information on which to base treatment decisions regarding cervical neoplasms
following biopsy testing. A similar classification scheme could provide guidance
to clinicians for the diagnosis and treatment of evolving SCC of the skin and as
such, we propose a similar classification using the terminology keratinocytic
intraepidermal neoplasia (KIN). This system is more reflective of the histology
and natural history of SCC and eliminates ambiguity in the terminology of lesions
currently referred to as AKs. The KIN classification defines features by which
individual specimens can be objectively graded and specific treatment
recommendations are made based on the grade of the lesion. We propose that the
term keratinocytic intraepidermal neoplasia (KIN) be used to define and describe
evolving SCC of the skin and that the term actinic (solar) keratosis be
eliminated.
PMID- 10188838
TI - Basal cell carcinoma or not? Histological variants and mimics of the most common
cutaneous malignancy.
AB - Basal cell carcinomas are the most common cutaneous malignancy encountered by
dermatologists. Although most basal cell carcinomas have typical features and are
easily diagnosed histologically, some basal cell carcinomas are problematic.
Because the best evidence suggests that basal cell carcinomas arise from
primitive stem cells that differentiate along follicular lines, it is not
uncommon that this tumor may resemble and be confused with a variety of benign
and malignant follicular and sweat gland tumors. This article will focus on some
common and rare histological variants that may produce confusion, as well as
salient features that will allow the correct diagnosis to be made.
PMID- 10188839
TI - Diagnosis: psoriasis or not? What are the clues?
AB - Psoriasis is a common inflammatory, hyperproliferative skin disorder that affects
1% to 2% of the population of Western Europe and the United States. Because the
clinical presentation of psoriasis is varied, many times the definitive diagnosis
depends on the histological examination. However, the histological changes of
psoriasis are as varied as the clinical presentations. Therefore, a combination
of histopathologic features must be present for the diagnosis of psoriasis to be
made. In this article, we review the clues for the histopathologic diagnosis of
each type and stage of psoriasis, such as psoriasis vulgaris, pustular psoriasis,
and erythrodermic psoriasis, as well as the histopathologic differential
diagnosis of these entities.
PMID- 10188840
TI - When to request immunofluorescence: practical hints.
AB - This review highlights important considerations in obtaining good skin biopsy
specimens to optimize results of direct immunofluorescence (IF) studies and also
summarizes the various patterns of cutaneous IF deposition and their associated
diagnoses. IF findings of immunobullous diseases, lupus erythematosus,
vasculitis, lichen planus, and erythema multiforme are included. The uses of
indirect IF studies are also reviewed including newer modifications that are
valuable in helping to diagnose epidermolysis bullosa acquisita and
paraneoplastic pemphigus.
PMID- 10188841
TI - Clark's nevus.
AB - "Clark's nevi" is the name we apply to lesions that have been referred to in the
past as dysplastic nevi or nevi with architectural and/or cytologic atypia. Our
criteria for this histopathologic diagnosis include such architectural features
as: (1) uneven distribution of melanocytes along the dermoepidermal junction; (2)
irregularly spaced junctional nests that sometimes bridge between rete; and (3)
ill-defined margins often characterized by a lentiginous growth pattern. If
dermal nests are present, the junctional component usually extends laterally for
some distance beyond the dermal nests. When there is cytologic atypia, it
involves scattered melanocytes. Clark's nevi are of doubtful significance if few
in number and occurring in a young patient in whom there is no family history of
melanoma. When many are found in a patient with a family history of melanoma,
their presence serves as a marker for dysplastic nevus syndrome (familial
atypical mole-melanoma syndrome). When Clark's nevi develop in patients older
than 40 or 50 years of age who have no family history of melanoma, their
significance is less clear. However, they might signify a defect in those
mechanisms that normally control formation and growth of melanocytic neoplasms.
PMID- 10188842
TI - Diagnosis: erythema nodosum or not?
AB - Erythema nodosum is the final common pathway to a myriad of insults and is
thought to be a hypersensitivity reaction centered in the subcutis. To recognize
the histological spectrum of erythema nodosum, one must be aware of the
morphologic chronology of the disease (early, fully developed, late) and its
clinical variants (erythema nodosum migrans). This article reviews the range of
changes that can be seen in this prototype of a septal panniculitis and describes
the diversity that may be accepted in the diagnosis. Differential diagnoses at
each stage of disease development are discussed. The criteria elaborated should
assist the pathologist in answering the clinician's query, "Erythema nodosum, or
not?"
PMID- 10188843
TI - Spitz nevus or melanoma?
AB - Spitz nevi are benign melanocytic neoplasms of children and young adults that can
be exceedingly difficult to distinguish from malignant melanomas. Although a
nearly definite diagnosis can be made in most cases, the histological distinction
between Spitz nevi and melanomas is equivocal in about 6% to 8% of cases. In
those cases, and perhaps even with presumed benign Spitz nevi, clear surgical
margins are desirable. The most helpful differentiating features of Spitz nevi
are patient age, sharp demarcation, symmetry, maturation of melanocytes at the
base, and epithelial hyperplasia. None of these criteria are completely reliable,
and multiple other criteria must be considered as well.
PMID- 10188844
TI - Diagnostic immunohistology: cutaneous lymphomas and pseudolymphomas.
AB - Differential diagnosis of cutaneous lymphoproliferative disorders represents one
of the most vexing problems in dermatology and dermatopathology.
Immunohistochemical and molecular techniques developed during the last 3 decades
have added new criteria for the differentiation of these diseases. In this
review, the main criteria for differential diagnosis of lymphoproliferative
disorders of the skin, with special emphasis on immunohistochemical features
detectable in routinely fixed paraffin-embedded tissue sections, are summarized.
When classifying cutaneous lymphoproliferative disorders, it is crucial to
remember that a correct diagnosis can only be reached when clinical data is
integrated with histopathologic, immunohistochemical, and molecular features.
PMID- 10188845
TI - Juvenile xanthogranuloma versus Langerhans cell histiocytosis (histiocytosis X).
PMID- 10188846
TI - Diagnosis: atypical fibroxanthoma or not? Evaluating spindle cell malignancies on
sun damaged skin: a practical approach.
AB - Poorly differentiated spindle cell malignancies on sun damaged skin frequently
pose a diagnostic challenge for dermatopathologists. The vast majority of these
neoplasms ultimately are diagnosed as either atypical fibroxanthoma (AFX),
spindle cell squamous cell carcinoma (SCSCC), or spindle cell melanoma (SCM), and
rarely leiomyosarcoma or angiosarcoma. Light microscopic clues may suggest one of
these neoplasms, but subtle and overlapping characteristics often render precise
diagnosis impossible based on morphological features alone. Immunohistochemistry
therefore is necessary to firmly and accurately diagnose the majority of spindle
cell malignancies on sun damaged skin. We summarize typical clinical and
histological findings associated with this group of malignancies and offer a
practical immunohistochemical approach to use in their diagnosis.
PMID- 10188847
TI - Diagnosis: alopecia areata or not?
AB - Alopecia areata is a common cause of hair loss in children and adults. In most
cases, the diagnosis is straight forward and is easily made based on the
patient's history and clinical presentation. However, in two specific scenarios,
the diagnosis can be difficult and may require a scalp biopsy. We present four
cases that illustrate these two problematic differentials: alopecia areata versus
trichotillomania in adolescent females; and diffuse alopecia areata versus
telogen effluvium versus androgenetic alopecia in adult women. Tables compare and
contrast the clinical and histopathologic features of these nonscarring localized
and diffuse alopecias.
PMID- 10188848
TI - The pathological distinction between "deep penetrating" dermatofibroma and
dermatofibrosarcoma protuberans.
AB - In selected cases, the clinicopathological distinction between deep penetrating
dermatofibroma (DPDF), which involves the subcutis, and dermatofibrosarcoma
protuberans (DFSPs) may be challenging. In most instances, attention to the
cytological constituency of the lesions and the overall architecture is
sufficient to make this separation. DPDF is typified by cellular heterogeneity,
including giant cells and lipidized histiocytes; when it extends into the
hypodermis, it does so either using the interlobular subcuticular fibrous septa
as scaffolds or in the form of broad pushing fronts of tumor. In contrast, DFSP
is a cytologically monotypical tumor, which entraps subcutaneous adipocytes
diffusely or grows in stratified horizontal plates in the hypodermis. In the
minority of cases where conventional morphological analysis of optimal biopsy
specimens is diagnostically indeterminate, immunostaining for CD34 and factor
XIIIa (FXIIIa) is helpful; it is also often necessary when a poorly
representative sample of the lesion has been obtained by the clinician.
Characteristically, DF is diffusely FXIIIa-reactive and CD34-negative, whereas
DFSP manifests the converse of those findings. Other markers such as Ki-M1p,
mutant p53 protein, and metallothionein may also provide adjuvant diagnostic
information in this context, as may the observation of abnormalities in
chromosomes 17 and 22 by direct karyotypic analysis.
PMID- 10188849
TI - British Association of Surgical Oncology Guidelines. The management of metastatic
bone disease in the United Kingdom. The Breast Specialty Group of the British
Association of Surgical Oncology.
AB - Bone metastases can present to a number of different specialties and their
successful management requires a coordinated approach with good liaison between
the specialists. Patients who respond to systemic therapy for their metastases
have a good chance of being alive at 3 years, and 20% will be alive at 5 years.
This means that it is worth palliating these patients properly. With this in
mind, the intention of this document is to try and improve the process of care
for women with metastatic bone disease from breast cancer. These guidelines
consider all aspects of care from diagnosis to assessment of response to
treatment, and describe the Quality Objectives that should be addressed at each
stage. The level of available evidence is indicated throughout the document where
possible. In considering diagnosis, the guidelines emphasize the value of having
a dedicated orthopaedic surgeon specifically linked to each Cancer Unit. The
attachment of a dedicated orthopaedic surgeon will ensure that mechanical
problems are correctly identified, and that actual or imminent fracture is
correctly managed. The latter is particularly important as the management of
pathological fractures is not the same as that of traumatic fractures. The
orthopaedic surgeon should also act as the liaison between his/her own Unit and
the tertiary spinal or neurosurgical centres as necessary. In addition,
empowering the radiologist means that the diagnostic process can be accelerated
and refined. The place of different investigations in diagnosis, including tumour
markers, is discussed. The guidelines emphasize the need for a definitive
diagnosis before treatment in the (rare) case of a solitary metastasis. The
treatment section discusses orthopaedic management, radiotherapy and systemic
treatments (endocrine therapy, chemotherapy and bisphosphonates). The guidelines
emphasize the emergency nature of spinal cord compression, describing the need
for fast access to assessment and for good liaison between specialists. It is
essential that these are available and widely publicized to ensure effective
management. The role of radiotherapy in both local pain relief and spinal cord
compression is discussed, and various techniques are described. Endocrine therapy
and chemotherapy are discussed in relation to the disease-free interval,
performance status, extent and site of metastatic disease, and oestrogen receptor
status. Specific chemotherapy regimes are not discussed as these are subject to
change and local protocols should be followed. The increasing evidence behind the
role of bisphosphonates is reviewed. With many unanswered questions about the
long-term use of this group of drugs, the guidelines offer a scoring system for
deciding which patients might benefit most from long-term bisphosphonate therapy.
The guidelines describe the possible ways of assessing response to treatment and
the difficulties that may be encountered, including a discussion of the role of
tumour markers in assessment of response. A final section looks at palliative
care principles in bone pain management, acknowledging the need for continuation
of good care throughout the patient's journey, from diagnosis onwards. We very
much hope these guidelines will stimulate individuals and institutions to improve
the process of delivering care to this group of patients.
PMID- 10188850
TI - Sentinel node biopsy in 70 unselected patients with breast cancer: increased
feasibility by using 10 mCi radiocolloid in combination with a blue dye tracer.
AB - AIMS: Lymphatic mapping and sentinel node (SN) biopsy in breast cancer contribute
to more accurate staging, while using less invasive techniques. The aim of this
study is to improve the accuracy and feasibility of this concept, increasing the
identification rate of the SN, by using an alternative technique. METHODS: In 70
unselected patients with primary breast cancer, of whom 51% had undergone
previous excisional biopsy, lymphatic mapping was performed using 10 mCi (370
MBq) 99mTc-nanocolloid peritumorally, combined with an intradermal blue dye
tracer. RESULTS: Lymphoscintigraphy showed one or more SN in 97% and harvest of
the SN was possible in all patients (identification rate 100%). Axillary
metastases were found in 39%. Sensitivity of the SN biopsy was high, both after
primary surgery (93%) and after previous surgery (100%). Internal mammary lymph
node biopsy following lymphatic mapping was attempted in all 24 patients (34%)
with parasternal SN visible on the scan and was successful in 15 patients,
revealing metastatic involvement in five patients. CONCLUSIONS: We conclude that
SN biopsy, using a higher dose of peritumoral radiocolloid tracer, combined with
intradermal blue dye tracer, increases feasibility in breast cancer, making this
concept applicable for all patients with primary breast cancer.
PMID- 10188851
TI - The effect of needle gauge and local anaesthetic on the diagnostic accuracy of
breast fine-needle aspiration cytology.
AB - AIMS: The value of breast fine needle aspiration cytology (FNAC) is well
established. This prospective study evaluates the effects of local anaesthetic
(LA) and different gauge needles on the diagnostic accuracy of breast FNAC.
METHODS: Aspirates were obtained from 59 consecutive excised breast tumours (51
malignant, eight benign) using green (21-G) and blue-hub (23-G) needles, both
before and after infiltration of LA at the aspiration site. RESULTS: There was
good agreement for the cytological diagnosis of each tumour when compared by
needle size (kappa = 0.85) and the presence of LA (kappa = 0.77). Diagnostic
sensitivity ranged from 88 to 92%. None of the differences were statistically
significant. In addition LA appeared to have no effect upon the cytological
grading of breast carcinomas (chi2 = 1.98, (df 3, P = 0.58). DISCUSSION: The use
of the smaller gauge blue-hub needle or LA does not appear to affect adversely
the diagnostic accuracy of breast FNAC. Whether using LA or the blue needle
routinely in the breast clinic will have an effect upon the discomfort
experienced during FNAC remains to be proven.
PMID- 10188852
TI - A tumour in the breast: vaccination granuloma as a differential diagnosis.
AB - AIMS: Breast cancer is the most frequent type of cancer in women; special
attention is therefore paid to tumours in the breast region. Vaccination
granuloma is a differential diagnosis of tumours in the upper part of the breast.
METHODS: All granulomatous lesions in the breast region since 1970 were retrieved
from the files of the Departments of Pathology at Odense University Hospital and
Svendborg Hospital. RESULTS: Fourteen cases with a histology compatible with
vaccination granuloma were found. Eight patients had a known history of tetanus
vaccination. The tumours were ovoid, or even rod-shaped, and measured between 8x3
mm and 12x10 mm. Histologically, there were necrotic foci surrounded by
histiocytes, lymphocytes, and plasma cells. Aluminium was detected by staining
with solochrome azurine. CONCLUSIONS: The possibility of a vaccination granuloma
should be kept in mind in patients with a palpable tumour in the upper part of
the breast, as well as in mammography screening conditions and in follow-up
patients after previous treatment for breast cancer.
PMID- 10188853
TI - Chronic post-treatment symptoms in patients with breast cancer operated in
different surgical units.
AB - AIMS: This study was designed to find out whether women operated in high volume
surgical units have less chronic symptoms than women operated in smaller volume
units. METHODS: A questionnaire was sent to 265 consecutive women treated at the
Department of Oncology, Helsinki University Central Hospital, from January to
June 1996. Of the patients, 129 were operated in hospitals experienced in breast
cancer surgery (high volume units = HVU) and 92 patients in district hospitals
with less experience in breast surgery (low volume units = LVU). RESULTS: Chronic
symptoms were less common in HVU than in LVU: chronic pain (56 vs. 43%, P<0.05)
or strange sensations (45 vs. 26%, P<0.01) in the ipsilateral arm or phantom
sensations in the removed breast (66 vs. 26%, P<0.001). The risk factors included
in the multivariate model for chronic pain in the breast area were: intensity of
acute post-operative pain, radiotherapy and depression and for the chronic arm
pain: low volume unit and depression. CONCLUSIONS: More careful surgical
technique seems to reduce the risk of chronic pain following treatment of breast
cancer. Chronic pain is associated with more intense post-operative pain and
depression.
PMID- 10188854
TI - Surgical treatment of malignant tumours of the sacrum.
AB - AIMS: We assessed the results of surgical treatment of malignant sacral tumours
and aimed to supply information on incidence and distribution of these lesions.
METHODS: Forty-six malignant cases out of 65 tumours of the sacrum were assessed
retrospectively. Three of the patients did not accept treatment. Surgical
treatment was applied to 23 (65.2%) of the remaining 43 patients. Surgical
techniques used were resection and PMMA (polymethylmethacrylate) application
through a posterior approach, sacral reconstruction, and resection through a
combined posterior and anterior approach. RESULTS: Twelve of the lesions were
primary while 34 were secondary. Among the primary sacrum tumours, the most
common was chordoma (six cases, forming 9.2% of all the sacral lesions). Of a
secondary sacral lesions, nine cases of breast carcinoma were found, forming the
most common group. The recurrence rate was 23.3%. CONCLUSIONS: Chordoma was the
most common primary sacral tumour, but found no incidence of giant cell tumour
which has been previously reported as the second most common primary sacral
tumour. We believe the posterior approach for resection of the tumour is
sufficient in most instances and lumbopelvic instability must be prevented by
reconstructive procedures.
PMID- 10188855
TI - The use of neoadjuvant CMF to avoid mastectomy.
AB - AIMS: Large operable cancers have traditionally been treated surgically by
mastectomy. More recently centres have investigated the use of neoadjuvant
chemotherapy to allow breast-conserving surgery. Between 1991 and 1995, a
prospective study into the response of large operable breast cancers to CMF
neoadjuvant chemotherapy was performed. METHODS: Patients with cancers requiring
mastectomy, and with or without clinically involved non-fixed lymph nodes, were
offered neoadjuvant CMF chemotherapy. Patients declining neoadjuvant treatment
underwent mastectomy and appropriate axillary surgery. Clinical response was
assessed after two cycles in the neoadjuvant group. Subsequent surgical or non
surgical management was planned after this. RESULTS: Thirty-eight patients were
suitable for neoadjuvant treatment. Twenty-two underwent two cycles of CMF and
were then reassessed. Seventy-three per cent achieved a response [three (14%)
complete remission, 13 (60%) partial remission]. Fifteen (68%) patients avoided
mastectomy, with six (27%) requiring no surgery at all with no clinically
detectable residual disease. Sixteen (42%) declined neoadjuvant chemotherapy and
opted for immediate mastectomy, seven of whom accepted chemotherapy post
operatively. After 3 years' follow-up there is no statistical difference in local
recurrence, distant recurrence or overall survival. CONCLUSION: Approximately 40%
of patients offered neoadjuvant chemotherapy will demand prompt surgical
treatment but will consider the use of adjuvant chemotherapy post-operatively.
Sixty-eight per cent of patients receiving neoadjuvant CMF will successfully
avoid mastectomy.
PMID- 10188856
TI - Occurrence of malignant non-germ cell components in primary mediastinal germ cell
tumours.
AB - METHODS: Thirty-five patients with primary mediastinal germ cell tumours (PMGCT)
underwent primary thoracotomy in a 30-year period (1965-1994). Of the 35
patients, 12 had benign teratomas, five pure seminomas and 18 non-seminomatous
germ cell tumours. RESULTS: Out of 18 non-seminomatous germ cell tumours, 14
comprised more than one malignant component. In two cases malignant teratomas had
an additional malignant non-germ cell component: one a mixed sarcomatous
component and the other a neuroendocrinal component. There were different methods
of treatment between 1965 and 1994. All but one of patients with seminomas
survived for 5 years. Among 18 patients with malignant PMGCT, all but two died
within 5 years (mean survival rate was 15 months). CONCLUSIONS: When planning
treatment of patients with malignant PMGCT we have to take into account the fact
that malignant non-germ-cell components may occur. In this circumstances,
surgical resection after initial chemotherapy is recommended.
PMID- 10188857
TI - Can p53 nuclear over-expression, Bcl-2 accumulation and PCNA status be of
prognostic significance in high-risk superficial and invasive bladder tumours?
AB - AIMS: To evaluate p53 and Bcl-2 expression and proliferating status (PCNA) in
subgroups of patients with high-risk superficial and invasive bladder cancer,
with relation to cancer progression and death, and to correlate the results with
established clinical prognostic factors. METHODS: Paraffin-embedded sections from
42 high-risk superficial (T1G2,T1G3) and 33 invasive (T2-T4aG3 N0M0) tumours were
investigated immunohistochemically for p53, Bcl-2 and PCNA. The median follow-up
was 52 months. RESULTS: In the cohort of superficial tumours, statistical
analysis showed that p53 and PCNA positivity were significant prognostic factors
(P-values: 0.008 and 0.006, respectively) for disease-specific death (DSD). When
life expectancy was evaluated (log-rank test), p53(+) (P = 0.015) and PCNA(+) (P
= 0.017) offered the most accurate prognosis compared to grade, tumour size and
multiplicity. Bcl-2 status had no significant effect on patient survival. In the
subset of muscle-invasive tumours we failed to demonstrate any important role of
p53, Bcl-2 or PCNA positivity. CONCLUSIONS: p53 and PCNA over-expression may
offer valuable additional prognostic information in high-risk subgroups of
superficial bladder tumours. From our results, Bcl-2 does not appear to
contribute significantly to the prognosis of these patients. None of the studied
markers offered prognostic information in muscle-invading disease.
PMID- 10188858
TI - Survival after radical treatment for transitional cell carcinoma of the bladder.
AB - AIMS: To investigate survival after radical treatment for transitional cell
carcinomas of the bladder. METHODS: This retrospective study included 135
patients with transitional cell carcinoma of the bladder undergoing radical
cystectomy or radiotherapy at Haukeland Hospital, Bergen, Norway, during the
period 1981-1986. Forty-five patients had cystectomy and 90 underwent external
high-dose radiotherapy. RESULTS: The overall 5- and 10-year survival rates were
39 and 23%, respectively. After cystectomy 10-year overall survival rates for
superficial and muscle-infiltrating tumours were 67 and 26%; after radiotherapy,
the corresponding survival rates for superficial and muscle-infiltrating tumours
were 26 and 5%, respectively. CONCLUSIONS: Long-term survival and cure can be
achieved after cystectomy in many patients with aggressive superficial or muscle
infiltrating bladder carcinoma. The introduction of orthotopic neobladder
reconstruction should encourage the use of cystectomy in patients with aggressive
superficial tumour.
PMID- 10188859
TI - Surgical treatment of renal cell carcinoma associated with Budd-Chiari syndrome:
report of four cases and review of the literature.
AB - AIMS: Renal cell carcinoma is sometimes associated with inferior vena caval
tumour thrombus, but occlusion of hepatic veins by the tumour thrombus causing
liver dysfunction, the so-called Budd Chiari syndrome, is relatively uncommon.
There are only a few reports in the literature which discuss this condition.
METHODS: Four cases admitted to our hospital over a 7-year period and eight cases
reported in detail in the English and the Japanese literature were included in
this study. They are classified into two groups: mild/silent, without liver
failure, and severe, with liver failure. RESULTS: Five patients were classified
as mild/silent and seven as severe. Clinical manifestations were mild in the
former cases and acute in the latter. Surgery was performed in four of the former
cases but only in one case of the latter cases. CONCLUSIONS: In mild cases,
surgical treatment seems to avoid imminent hepatic failure effectively and should
be performed as soon as possible. In such cases Budd Chiari syndrome in itself
does not affect the prognosis. In severe cases, however, surgical treatment is
very difficult and risky due to the existing hepatic failure.
PMID- 10188860
TI - Anal submucosal injection: a novel modality for the treatment of advanced rectal
cancer.
AB - AIMS: To investigate the efficacy of methotrexate (MTX) submucosal anal injection
in the treatment of advanced rectal cancer. METHODS: Thirty-six patients (age 36
66 years; 21 men, 15 women; 20 patients with stage T3N1M0 and 16 with T4N1M1
rectal cancer) were injected with MTX in the anal submucosa. A comparative group
of eight patients (age 38-62 years: five men, three women; four with T3N1M0 and
four with T4N1M1 rectal cancer) was injected with MTX intravenously. The dose in
both groups was 100 mg every 5 days for five consecutive doses and the course was
repeated at 3-week intervals. MTX serum and tumour concentrations were estimated
30 and 60 min after MTX injection. The patients received MTX as outpatients.
RESULTS: In the anal group, six of 20 patients with T3 tumour showed complete
tumour regression and were alive 28-46 months after the start of the treatment.
Partial response occurred in 25 patients: 14 of stage T3 and 11 of T4. The 14 T3
patients underwent combined excision operation and 9/14 were alive 26-68 months
from the time of operation. Five of the 16 T4 patients showed tumour and
metastatic progression. Mild toxicity occurred in six of 36 patients while the
haematological reserve was unchanged in all the patients. All eight patients in
the parenteral group showed progress of the malignant lesions under treatment and
toxic manifestations were so severe that the treatment had to be interrupted. The
MTX concentration in serum was significantly higher after parenteral than after
anal injection, while in tumour tissue it was higher after anal administration.
CONCLUSIONS: The results show that MTX submucosal anal injection is effective in
treatment of T3 rectal cancer due to high MTX concentration in the tumour.
Toxicity was mild owing to low level of serum MTX. The anal route of
administration is safe, well tolerated and can be used on an outpatient basis.
PMID- 10188861
TI - Complications following gastric transposition after total laryngo-pharyngectomy.
AB - AIMS: To investigate restoration of the pharynx after total laryngo-pharyngectomy
(TLP), one of the major problems in head and neck surgery. METHODS: A
retrospective analysis of 60 patients undergoing total laryngo-pharyngectomy with
gastric transposition was performed between June 1991 and June 1996. The analysis
focused on morbidity, mortality and long-term function following gastric
transposition. RESULTS: The post-operative mortality was 8.3% and the peri
operative morbidity 31.2%. The average hospital stay was 15 days. Immediate
restoration of swallowing was achieved in 83% of patients. CONCLUSIONS: Gastric
transposition after total laryngo-pharyngectomy is a safe procedure and can be
performed with low mortality, acceptable morbidity and good long-term function.
PMID- 10188862
TI - Tumour biology, chaos and non-linear dynamics.
PMID- 10188863
TI - Local excision of periampullary villous tumours of the duodenum.
AB - AIMS: Our goal was to describe our technical approach to transduodenal submucosal
resection of periampullary villous tumours of the duodenum. METHODS: We address
technical tips to aid in exposure and reconstruction of pancreaticobiliary
continuity with special reference to the indications for adding biliary
sphincteroplasty, pancreatic septectomy, and local resection of neoplasms
extending past the immediate ampullary mucosa into the bile and/or pancreatic
ducts. CONCLUSIONS: This approach has proven safe, easy and without significant
morbidity.
PMID- 10188864
TI - Congenital infantile fibrosarcoma.
AB - Infantile fibrosarcoma is a rare tumour in the paediatric age group. It occurs
mainly in children below the age of 5 years. About 200 cases have been reported
in the literature so far, very few of them in new-borns. We present here a case
of infantile fibrosarcoma in a 27-day-old baby.
PMID- 10188865
TI - A rare case of benign mesenchymoma of the breast in a man.
AB - The term 'benign mesenchymoma' was first used by Stout in 1948 and has since been
widely adopted to describe benign tumours made up of a mixture of mesenchymal
tissues which had previously been called by many names, such as hamartoma and
angiolipoma. This tumour is most commonly found in the renal and perirenal
tissue. Benign mesenchymomas arising in the breast are extremely rare. We
present, to our knowledge, the first reported case of benign mesenchymoma in a
male breast. The clinical presentation, course and treatment of the patient are
discussed.
PMID- 10188866
TI - Secretory breast carcinoma in a boy.
AB - Secretory breast carcinoma is a very rare condition in boys. An 11-year-old boy
with secretory breast carcinoma is presented here. Modified radical mastectomy
was performed by irradiation and chemotherapy because of axillary metastasis.
There was no local recurrence or distant metastases in the follow-up period of 14
months.
PMID- 10188867
TI - Parathyroid carcinoma secondary to prolonged hyperplasia in chronic renal failure
and in coeliac disease.
AB - The presentation of parathyroid carcinoma in patients with chronic renal failure
is rare, although with improvements in life expectancy associated with this
condition there have now been 12 reported cases, including the first case we
report here. It has been proposed that in these cases there has been a malignant
transformation of benign parathyroid hyperplastic tissue. We also report the
first case of parathyroid carcinoma associated with coeliac disease and suggest
that the same mechanism may be responsible. We review the presentation,
diagnosis, treatment and natural history of the disease.
PMID- 10188868
TI - Possible branchiogenic carcinoma coinciding with metastatic papillary thyroid
carcinoma.
AB - We report the discovery of a cystic lesion of flat lining epithelium with areas
of squamous carcinoma, associated with metastatic cervical nodes of a papillary
thyroid cancer, and discuss the diagnostic possibilities.
PMID- 10188869
TI - Long-term survival after extended surgical resection of melanoma metastasis and
immunotherapy.
AB - A patient with a huge melanoma metastasis to the left adrenal gland was treated
by multivisceral surgical resection. Progression of disease could be controlled
by systemic immunotherapy resulting in long-term survival. In selected cases,
above all with late manifestation of distant melanoma metastases, even major
surgical resection of such lesions can be worthwhile.
PMID- 10188870
TI - Enteric epithelium progressing through dysplasia to adenocarcinoma within the
vagina.
PMID- 10188871
TI - Biological effects of naturally occurring and man-made fibres: in vitro
cytotoxicity and mutagenesis in mammalian cells.
AB - Cytotoxicity and mutagenicity of tremolite, erionite and the man-made ceramic
(RCF-1) fibre were studied using the human-hamster hybrid A(L) cells. Results
from these fibres were compared with those of UICC Rhodesian chrysotile fibres.
The A(L) cell mutation assay, based on the S1 gene marker located on human
chromosome 11, the only human chromosome contained in the hybrid cell, has been
shown to be more sensitive than conventional assays in detecting deletion
mutations. Tremolite, erionite and RCF-1 fibres were significantly less cytotoxic
to A(L) cells than chrysotile. Mutagenesis studies at the HPRT locus revealed no
significant mutant yield with any of these fibres. In contrast, both erionite and
tremolite induced dose-dependent S1- mutations in fibre-exposed cells, with the
former inducing a significantly higher mutant yield than the latter fibre type.
On the other hand, RCF-1 fibres were largely non-mutagenic. At equitoxic doses
(cell survival at approximately 0.7), erionite was found to be the most potent
mutagen among the three fibres tested and at a level comparable to that of
chrysotile fibres. These results indicate that RCF-1 fibres are non-genotoxic
under the conditions used in the studies and suggest that the high mesothelioma
incidence previously observed in hamster may either be a result of selective
sensitivity of hamster pleura to fibre-induced chronic irritation or as a result
of prolonged fibre treatment. Furthermore, the relatively high mutagenic
potential for erionite is consistent with its documented carcinogenicity.
PMID- 10188872
TI - Induction of apoptosis in myeloid leukaemic cells by ribozymes targeted against
AML1/MTG8.
AB - The translocation (8;21)(q22;q22) is a karyotypic abnormality detected in acute
myeloid leukaemia (AML) M2 and results in the formation of the chimeric fusion
gene AML1/MTG8. We previously reported that two hammerhead ribozymes against
AML1/MTG8 cleave this fusion transcript and also inhibit the proliferation of
myeloid leukaemia cell line Kasumi-1 which possesses t(8;21)(q22;q22). In this
study, we investigated the mechanisms of inhibition of proliferation in myeloid
leukaemic cells with t(8;21)(q22;q22) by ribozymes. These ribozymes specifically
inhibited the growth of Kasumi-1 cells, but did not affect the leukaemic cells
without t(8;21)(q22;q22). We observed the morphological changes including
chromatin condensation, fragmentation and the formation of apoptotic bodies in
Kasumi-1 cells incubated with ribozymes for 7 days. In addition, DNA ladder
formation was also detected after incubation with ribozymes which suggested the
induction of apoptosis in Kasumi-1 cells by the AML1/MTG8 ribozymes. However, the
ribozymes did not induce the expression of CD11b and CD14 antigens in Kasumi-1
cells. The above data suggest that these ribozymes therefore inhibit the growth
of myeloid leukaemic cells with t(8;21)(q22;q22) by the induction of apoptosis,
but not differentiation. We conclude therefore that the ribozymes targeted
against AML1/MTG8 may have therapeutic potential for patients with AML carrying
t(8;21)(q22;q22) while, in addition, the product of the chimeric gene is
responsible for the pathogenesis of myeloid leukaemia.
PMID- 10188873
TI - Influence of O6-benzylguanine on the anti-tumour activity and normal tissue
toxicity of 1,3-bis(2-chloroethyl)-1-nitrosourea and molecular combinations of 5
fluorouracil and 2-chloroethyl-1-nitrosourea in mice.
AB - Previous studies have demonstrated that novel molecular combinations of 5
fluorouracil (5FU) and 2-chloroethyl-1-nitrosourea (CNU) have good preclinical
activity and may exert less myelotoxicity than the clinically used nitrosoureas
such as 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). This study examined the
effect of O6-alkylguanine-DNA-alkyltransferase (ATase) depletion by the
pseudosubstrate O6-benzylguanine (BG) on the anti-tumour activity and normal
tissue toxicity in mice of three such molecular combinations, in comparison with
BCNU. When used as single agents at their maximum tolerated dose, all three novel
compounds produced a significant growth retardation of BCNU-resistant murine
colon and human breast xenografts. This in vivo anti-tumour effect was
potentiated by BG, but was accompanied by severe myelotoxicity as judged by
spleen colony forming assays. However, while tumour resistance to BCNU was
overcome using BG, this was at the expense of enhanced bone marrow, gut and liver
toxicity. Therefore, although this ATase-depletion approach resulted in improved
anti-tumour activity for all three 5-FU:CNU molecular combinations, the
potentiated toxicities in already dose-limiting tissues indicate that these types
of agents offer no therapeutic advantage over BCNU when they are used together
with BG.
PMID- 10188874
TI - The flavonoid galangin is an inhibitor of CYP1A1 activity and an
agonist/antagonist of the aryl hydrocarbon receptor.
AB - The effect of the dietary flavonoid galangin on the metabolism of 7,12
dimethylbenz[a]anthracene (DMBA), the activity of cytochrome P450 1A1 (CYP1A1),
and the expression of CYP1A1 in MCF-7 human breast carcinoma cells was
investigated. Galangin inhibited the catabolic breakdown of DMBA, as measured by
thin-layer chromatography, in a dose-dependent manner. Galangin also inhibited
the formation of DMBA-DNA adducts, and prevented DMBA-induced inhibition of cell
growth. Galangin caused a potent, dose-dependent inhibition of CYP1A1 activity,
as measured by ethoxyresorufin-O-deethylase activity, in intact cells and in
microsomes isolated from DMBA-treated cells. Analysis of the inhibition kinetics
by double-reciprocal plot demonstrated that galangin inhibited CYP1A1 activity in
a noncompetitive manner. Galangin caused an increase in the level of CYP1A1 mRNA,
indicating that it may be an agonist of the aryl hydrocarbon receptor, but it
inhibited the induction of CYP1A1 mRNA by DMBA or by 2,3,5,7-tetrachlorodibenzo-p
dioxin (TCDD). Galangin also inhibited the DMBA- or TCDD-induced transcription of
a reporter vector containing the CYP1A1 promoter. Thus, galangin is a potent
inhibitor of DMBA metabolism and an agonist/antagonist of the AhR, and may prove
to be an effective chemopreventive agent.
PMID- 10188875
TI - Inhibition of invasion and induction of apoptotic cell death of cancer cell lines
by overexpression of TIMP-3.
AB - Dysregulation of matrix degrading metalloproteinase enzymes (MMPs) leads to
increased extracellular matrix turnover, a key event in the local invasion and
metastasis of many tumours. The tissue inhibitors of metalloproteinases (TIMPs)
limit the activity of MMPs, which suggests their use in gene therapy. We have
previously shown that overexpression of TIMP-1, -2 or -3 inhibits vascular smooth
muscle and melanoma cell invasion, while TIMP-3 uniquely promotes apoptosis. We
have therefore sought to determine whether TIMP-3 can inhibit invasion and
promote apoptosis in other cancer cell types. Adenoviral-mediated overexpression
of TIMP-3 inhibited invasion of HeLa and HT1080 cells through artificial basement
membrane to similar levels as that achieved by TIMP-1 and -2. However, TIMP-3
uniquely promoted cell cycle entry and subsequent death by apoptosis. Apoptosis
was confirmed by morphological analysis, terminal dUTP nick end labelling (TUNEL)
and flow cytometry. The apoptotic phenotype was mimicked by addition of exogenous
recombinant TIMP-3 to uninfected cultures demonstrating that the death signal is
initiated extracellularly and that a bystander effect exists. These results show
that TIMP-3 inhibits invasion in vitro and promotes apoptosis in cancer cell type
of differing origin. This clearly identifies the potential of TIMP-3 for gene
therapy of multiple cancer types.
PMID- 10188876
TI - New semisynthetic vinca alkaloids: chemical, biochemical and cellular studies.
AB - A new semisynthetic anti-tumour bis-indol compound, KAR-2 [3'-(beta-chloroethyl)
2',4'-dioxo-3,5'-spiro-oxazolidino-4-dea cetoxy-vinblastine] with lower toxicity
than vinca alkaloids used in chemotherapy binds to calmodulin but, in contrast to
vinblastine, does not exhibit anti-calmodulin activity. To investigate whether
the modest chemical modification of bis-indol structure is responsible for the
lack of anti-calmodulin potency and for the different pharmacological effects,
new derivatives have been synthesized for comparative studies. The synthesis of
the KAR derivatives are presented. The comparative studies showed that the spiro
oxazolidino ring and the substitution of a formyl group to a methyl one were
responsible for the lack of anti-calmodulin activities. The new derivatives,
similar to the mother compounds, inhibited the tubulin assembly in polymerization
tests in vitro, however their inhibitory effect was highly dependent on the
organization state of microtubules; bundled microtubules appeared to be resistant
against the drugs. The maximal cytotoxic activities of KAR derivatives in in vivo
mice hosting leukaemia P388 or Ehrlich ascites tumour cells appeared similar to
that of vinblastine or vincristine, however significant prolongation of life span
could be reached with KAR derivatives only after the administration of a single
dose. These studies plus data obtained using a cultured human neuroblastoma cell
line showed that KAR compounds displayed their cytotoxic activities at
significantly higher concentrations than the mother compounds, although their
antimicrotubular activities were similar in vitro. These data suggest that
vinblastine/vincristine damage additional crucial cell functions, one of which
could be related to calmodulin-mediated processes.
PMID- 10188877
TI - Fibroblast radiosensitivity measured using the comet DNA-damage assay correlates
with clonogenic survival parameters.
AB - A study was made of the neutral comet assay as a potential method for measuring
normal cell radiosensitivity. Eleven fibroblast strains were studied comprising
nine derived from vaginal biopsies from pretreatment cervical cancer patients and
two strains from radiosensitive individuals. DNA double strand break (dsbs) dose
response curves for both initial and residual (20-h repair time) damage were
obtained over the dose range 0-240 Gy, with slopes varying 3.2 and 8-fold
respectively. Clonogenic cell survival parameters were available for all the cell
strains following both high- and low-dose rate irradiation. There were no
correlations between the dose-response slope of the initial level of DNA dsbs and
parameters that mainly describe the initial portion of clonogenic radiation
survival curves (SF2, alpha, D). A significant correlation (r = -0.63, P = 0.04)
was found between the extent of residual DNA dsbs and clonogenicity for all 11
fibroblast strains. The parameter showing the highest correlation with fibroblast
cell killing (D) for the nine normal fibroblasts alone was the ratio of
initial/residual DNA dsb dose-response slope (r = 0.80, P = < 0.01). A
significant correlation (r = -0.67, P = 0.03) with clonogenic radiosensitivity
was also found for all 11 cell strains when using the ratio of initial/residual
DNA dsb damage at a single dose of 180 Gy. This study shows that fibroblast
radiosensitivity measured using the neutral comet assay correlates with
clonogenic radiation survival parameters, and therefore may have potential value
in predictive testing of normal tissue radiosensitivity.
PMID- 10188878
TI - Hypoxia significantly reduces aminolaevulinic acid-induced protoporphyrin IX
synthesis in EMT6 cells.
AB - We have studied the effects of hypoxia on aminolaevulinic acid (ALA)-induced
protoporphyrin IX (PpIX) synthesis in EMT6 monolayer cultures characterized by
different cell densities and proliferation rates. Specifically, after ALA
incubation under hypoxic or normoxic conditions, we detected
spectrofluorometrically the PpIX content of the following populations: (a) low
density exponentially growing cells; (b) high-density fed-plateau cells; and (c)
high-density unfed-plateau cells. These populations were selected either for the
purpose of comparison with other in vitro studies (low-density exponentially
growing cells) or as representatives of tumour regions adjacent to (high-density
fed-plateau cells) and further away from (high-density unfed-plateau cells)
capillaries. The amount of PpIX per cell produced by each one of these
populations was higher after normoxic ALA incubation. The magnitude of the effect
of hypoxia on PpIX synthesis was dependent on cell density and proliferation
rate. A 42-fold decrease in PpIX fluorescence was observed for the high-density
unfed-plateau cells. PpIX production by the low-density exponential cells was
affected the least by ALA incubation under hypoxic conditions (1.4-fold
decrease), whereas the effect on the high-density fed-plateau population was
intermediate (20-fold decrease).
PMID- 10188879
TI - Bystander killing of tumour cells by antibody-targeted enzymatic activation of a
glucuronide prodrug.
AB - RHI-betaG-PEG, formed by linking poly(ethylene glycol)-modified beta
glucuronidase to Mab RH1, was employed to examine bystander killing of antigen
negative N1S1 rat hepatoma cells by activation of a glucuronide prodrug (BHAMG)
of p-hydroxyaniline mustard (pHAM) at antigen-positive AS-30D rat hepatoma cells.
Sequential treatment of cells with 10 microg ml(-1) RH1-betaG-PEG and 20 microM
BHAMG was not toxic to N1S1 cells but killed 99% of AS-30D cells. Over 98% of
N1S1 cells, however, were killed in mixed populations containing as few as 2% AS
30D cells after identical treatment, demonstrating an in vitro bystander effect.
Subcutaneous injection of AS-30D and N1S1 cells in BALB/c nu/nu mice produced
solid tumours containing both cells. Uptake of radiolabelled RH1-betaG-PEG in
solid AS-30D and mixed AS-30D/N1S1 tumours was 11.6 and 9.3 times greater than a
control antibody conjugate 120 h after i.v. injection. Intravenous treatment with
RH1-betaG-PEG and BHAMG cured seven of seven nude mice bearing solid s.c. AS-30D
tumours and significantly delayed, compared with control conjugate and prodrug
treatment, the growth of mixed N1S1/AS-30D tumours with one cure, showing that
targeted activation of BHAMG kills bystander tumour cells in vivo.
PMID- 10188880
TI - Increased platinum accumulation in SA-1 tumour cells after in vivo
electrochemotherapy with cisplatin.
AB - Electrochemotherapy is an anti-tumour treatment that utilizes locally delivered
electric pulses to increase cytotoxicity of chemotherapeutic drugs. The aim of
our study was to determine whether anti-tumour effectiveness of
electrochemotherapy with cisplatin is a consequence of increased plasma membrane
permeability caused by electroporation that enables cisplatin binding to DNA. For
this purpose, anti-tumour effectiveness of electrochemotherapy was evaluated on
SA-1 tumours treated with electric pulses 3 min after intravenous injection of
cisplatin (4 mg kg(-1)). Anti-tumour effectiveness was correlated with platinum
accumulation in tumours and the amount of platinum bound to DNA, as determined by
atomic absorption spectrometry. In tumours treated with electrochemotherapy, cell
kill was increased by a factor of 20 compared with treatment with cisplatin only,
as determined from tumour growth curves. The amount of platinum bound to DNA and
platinum content in the tumours treated by electrochemotherapy was approximately
two times higher than in cisplatin-treated tumours. Based on our results, we
conclude that in vivo application of electric pulses potentiates anti-tumour
effectiveness of cisplatin by electroporation that consequently results in
cisplatin increased delivery into the cells. In addition, besides
electroporation, immune system and tumour blood flow changes could be involved in
the observed anti-tumour effectiveness of electrochemotherapy.
PMID- 10188881
TI - Stimulation of tumour growth by wound-derived growth factors.
AB - The goal of this work was to determine the molecular basis for the induction of
tumour vascularization and progression by injury. Magnetic resonance imaging
(MRI) studies demonstrated that administration of wound fluid derived from
cutaneous injuries in pigs reduced the lag for vascularization and initiation of
growth of C6 glioma spheroids, implanted in nude mice, and accelerated tumour
doubling time. The former effect can be attributed to the angiogenic capacity of
wound fluid as detected in vivo by MRI, and in vitro in promoting endothelial
cell proliferation. The latter effect, namely the induced rate of tumour growth,
is consistent with the angiogenic activity of wound fluid as well as with the
finding that wound fluid was directly mitogenic to the tumour cells, and
accelerated growth of C6 glioma in spheroid culture. Of the multiple growth
factors present in wound fluid, two key factors, heparin-binding epidermal growth
factor (EGF)-like growth factor (HB-EGF) and platelet-derived growth factor
(PDGF), were identified as the dominant mitogens for C6 glioma, and inhibition of
their activity using specific neutralizing antibodies suppressed the mitogenic
effect of wound fluid on DNA synthesis in C6 glioma. This study suggests that the
stimulatory effect of injury on tumour progression can possibly be attenuated by
therapeutic targeting directed against a limited number of specific growth
factors.
PMID- 10188882
TI - Cyclooxygenase 2 is up-regulated and localized to macrophages in the intestine of
Min mice.
AB - Expression of cyclooxygenase 2 (COX-2) is believed to play an important role in
adenoma formation in murine polyposis models, and inhibition of COX-2 activity
may, at least, partly explain the chemopreventative activity of non-steroidal
anti-inflammatory drugs against colorectal cancer in humans. However, the
mechanism by which COX-2 acts in intestinal tumorigenesis remains unresolved
because of conflicting data on the cellular localization of COX-2 in intestinal
mucosa. Using immunohistochemistry with specific COX-2 antiserum, we have shown
that COX-2 protein is localized to interstitial cells at the base of and within
adenomas of the small and large intestine of multiple intestinal neoplasia (Min)
mice. No COX-2 staining was observed in dysplastic epithelial cells within
adenomas or in histologically normal epithelium. Moreover, COX-2 staining was
observed in lamina propria cells of histologically normal intestine of Min mice.
No staining was demonstrated in wild-type littermates. The rat monoclonal
antibody F4/80 was used to show that COX-2-positive cells represented a subset of
the macrophage population present in the intestine of Min mice. Localization of
COX-2 to macrophages implies a paracrine effect of COX-2 function on epithelial
cells in adenomas and also on histologically normal epithelium. Up-regulation of
COX-2 expression in lamina propria macrophages may precede loss of the second
functional Apc allele in epithelial cells before adenoma formation in the Min
mouse model of intestinal tumorigenesis.
PMID- 10188883
TI - Effects of bryostatin-1 on chronic myeloid leukaemia-derived haematopoietic
progenitors.
AB - Bryostatin-1 belongs to the family of macrocyclic lactones isolated from the
marine bryozoan Bugula neritina and is a potent activator of protein kinase C
(PKC). Bryostatin has been demonstrated to possess both in vivo and in vitro anti
leukaemic potential. In samples derived from chronic myeloid leukaemia (CML)
patients, it has been demonstrated that bryostatin-1 induces a macrophage
differentiation, suppresses colony growth in vitro and promotes cytokine
secretion from accessory cells. We investigated the effect of bryostatin-1
treatment on colony-forming unit-granulocyte macrophage (CFU-GM) capacity in the
presence of accessory cells, using mononuclear cells, as well as in the absence
of accessory cells using purified CD34-positive cells. Cells were obtained from
14 CML patients as well as from nine controls. Moreover, CD34-positive cells
derived from CML samples and controls were analysed for stem cell frequency and
ability using the long-term culture initiating cell (LTCIC) assay at limiting
dilution. Individual colonies derived from both the CFU-GM and LTCIC assays were
analysed for the presence of the bcr-abl gene with fluorescence in situ
hybridization (FISH) to evaluate inhibition of malignant colony growth. The
results show that at the CFU-GM level bryostatin-1 treatment resulted in only a
1.4-fold higher reduction of CML colony growth as compared to the control
samples, both in the presence and in the absence of accessory cells. However, at
the LTCIC level a sixfold higher reduction of CML growth was observed as compared
to the control samples. Analysis of the LTCICs at limiting dilution indicates
that this purging effect is caused by a decrease in output per malignant LTCIC
combined with an increase in the normal stem cell frequency. It is concluded that
bryostatin-1 selectively inhibits CML growth at the LTCIC level and should be
explored as a purging modality in CML.
PMID- 10188884
TI - Phase II study of RC-160 (vapreotide), an octapeptide analogue of somatostatin,
in the treatment of metastatic breast cancer.
AB - RC-160 (octastatin/vapreotide) is a potent octapeptide analogue of somatostatin
with growth inhibitory activity in experimental tumours in vitro and in vivo,
including breast cancer. We evaluated the efficacy and tolerability of high-dose
RC-160, 3 mg day(-1) on week 1 increased to 4.5 mg day(-1) for weeks 2-4 and
subsequently 6 mg day(-1) until the end of treatment, administered by continuous
subcutaneous infusion in the management of 14 women with previously treated
metastatic breast cancer. The age range was 37-80 years (median 58.5 years) and
performance status 0-2. The treatment was well tolerated with no dose reductions
being required. No grade 3 or 4 toxicities were seen. Abscess formation developed
at the infusion site in eight patients and erythema and discomfort was seen in a
further three patients. A significant reduction in IGF-I levels occurred by day 7
and was maintained throughout the treatment. The lowest dose of RC-160 produced
the maximal IGF-I response. Although there was no reduction in prolactin levels
in patients whose baseline levels were normal, elevated prolactin levels found in
three patients fell to within the normal range 7 days after commencing RC-160
treatment. A small but significant rise in fasting blood glucose levels was also
recorded, the highest level on treatment being 7.6 mmol l(-1). No objective
tumour responses were observed, all patients showing disease progression within 3
months of commencing treatment. These findings demonstrate that high-dose RC-160,
administered as a continuous subcutaneous infusion, can reduce serum levels of
the breast growth factors IGF-I and prolactin but is ineffective in the
management of metastatic breast cancer. Encouraging preclinical anti-tumour
activity and the favourable toxicity profile in patients suggest the merit of
future studies combining RC-160 with anti-oestrogen, cytotoxic and anti
angiogenic agents.
PMID- 10188885
TI - Markov model and markers of small cell lung cancer: assessing the influence of
reversible serum NSE, CYFRA 21-1 and TPS levels on prognosis.
AB - High serum NSE and advanced tumour stage are well-known negative prognostic
determinants of small cell lung cancer (SCLC) when observed at presentation.
However, such variables are reversible disease indicators as they can change
during the course of therapy. The relationship between risk of death and marker
level and disease state during treatment of SCLC chemotherapy is not known. A
total of 52 patients with SCLC were followed during cisplatin-based chemotherapy
(the median number of tumour status and marker level assessments was 4). The time
homogeneous Markov model was used in order to analyse separately the prognostic
significance of change in the state of the serum marker level (NSE, CYFRA 21-1,
TPS) or the change in tumour status. In this model, transition rate intensities
were analysed according to three different states: alive with low marker level
(state 0), alive with high marker level (state 1) and dead (absorbing state). The
model analysing NSE levels showed that the mean time to move out of state 'high
marker level' was short (123 days). There was a 44% probability of the opposite
reversible state 'low marker level' being reached, which demonstrated the
reversible property of the state 'high marker level'. The relative risk of death
from this state 'high marker level' was about 2.24 times greater in comparison
with that of state 0 'low marker level' (Wald's test; P < 0.01). For patients in
state 'high marker level' at time of sampling, the probability of death increased
dramatically, a transition explaining the rapid decrease in the probability of
remaining stationary at this state. However, a non-nil probability to change from
state 1 'high marker level' to the opposite transient level, state 0 'low marker
level', was observed suggesting that, however infrequently, patients in state 1
'high marker level' might still return to state 0 'low marker level'. Almost
similar conclusions can be drawn regarding the three-state model constructed
using the tumour response status. For the two cytokeratin markers, the Markov
model suggests the lack of a true reversible property of these variables as there
was only a very weak probability of a patient returning to state 'low marker
level' once having entered state 'high marker level'. In conclusion, The Markov
model suggests that the observation of an increase in serum NSE level or a lack
of response of the disease at any time during follow-up (according to the
homogeneous assumption) was strongly associated with a worse prognosis but that
the reversion to a low mortality risk state remains possible.
PMID- 10188886
TI - Diagnostic and therapeutic approaches for nonmetastatic breast cancer in Canada,
and their associated costs.
AB - In an era of fiscal restraint, it is important to evaluate the resources required
to diagnose and treat serious illnesses. As breast cancer is the major malignancy
affecting Canadian women, Statistics Canada has analysed the resources required
to manage this disease in Canada, and the associated costs. Here we report the
cost of initial diagnosis and treatment of nonmetastatic breast cancer, including
adjuvant therapies. Treatment algorithms for Stages I, II, and III of the disease
were derived by age group (< 50 or > or = 50 years old), principally from
Canadian cancer registry data, supplemented, where necessary, by the results of
surveys of Canadian oncologists. Data were obtained on breast cancer incidence by
age, diagnostic work-up, stage at diagnosis, initial treatment, follow-up
practice, duration of hospitalization and direct care costs. The direct health
care costs associated with 'standard' diagnostic and therapeutic approaches were
calculated for a cohort of 17,700 Canadian women diagnosed in 1995. Early stage
(Stages I and II) breast cancer represented 87% of all incident cases, with 77%
of cases occurring in women > or = 50 years. Variations were noted in the rate of
partial vs total mastectomy, according to stage and age group. Direct costs for
diagnosis and initial treatment ranged from $8014 for Stage II women > or = 50
years old, to $10,897 for Stage III women < 50 years old. Except for Stage III
women < 50 years old, the largest expenditure was for hospitalization for
surgery, followed by radiotherapy costs. Chemotherapy was the largest cost
component for Stage III women < 50 years old. This report describes the cost of
diagnosis and initial treatment of nonmetastatic breast cancer in Canada,
assuming current practice patterns. A second report will describe the lifetime
costs of treating all stages of breast cancer. These data will then be
incorporated into Statistics Canada's Population Health Model (POHEM) to perform
cost-effectiveness studies of new therapeutic interventions for breast cancer,
such as the cost-effectiveness of day surgery, or of radiotherapy to all breast
cancer patients undergoing breast surgery.
PMID- 10188887
TI - Cystic lymph node metastases of squamous cell carcinoma of Waldeyer's ring
origin.
AB - We analysed in a retrospective study the frequency of cystic lymph node (LN)
metastases in neck dissection specimens of 123 patients with primary squamous
cell carcinoma (SCC) arising in the palatine tonsils (62 M/14 F), the base of the
tongue (38 M/5 F) and the nasopharynx (2 M/2 F). Eighty-two per cent of patients
had metastases (64 tonsillar SCC, 33 base of tongue SCC and all four nasopharynx
SCC) in 368 LN of a total 2298 sampled LN. Thirty-nine per cent of patients had
exclusively solid metastases and 37% of patients had exclusively cystic
metastases. A total of 62 patients had some signs of cyst formation in one or
more metastatically affected LN (27 with only histological evidence of cyst
formation with luminal diameters < 5 mm, 35 with clinically detectable cyst with
luminal diameter > 5 mm). Cystic metastases were more common in patients with SCC
of the base of the tongue (P = 0.005), while solitary clinically evident cystic
metastasis with lumina > 5 mm were found exclusively in tonsillar carcinoma (P =
0.024). In comparison with solid metastases, cyst formation was associated with N
categories (N2b and N3, P = 0.005) in SCC of the base of the tongue origin. No
such association was observed for tonsillar SCC (P = 0.65). The primary mechanism
of cyst formation was cystic degeneration.
PMID- 10188888
TI - The role of tumour markers in predicting skeletal metastases in breast cancer
patients with equivocal bone scintigraphy.
AB - Bone scintigraphy (BS) is commonly performed in the staging and postoperative
monitoring of breast cancer. Nevertheless, due to low specificity it often
demonstrates hot spots with equivocal interpretation, which may be misleading in
the management of these patients. The aim of this study was to assess the value
of a serum tumour marker panel in selecting among the patients with equivocal BS
those with bone metastases. Between January 1986 and December 1995, 297 breast
cancer patients were followed-up after mastectomy with serial determinations of a
CEA-TPA-CA15.3 tumour marker panel, BS and liver echography. The tumour marker
panel was used to select patients with equivocal BS for examination of suspicious
bone areas by further imaging techniques. Up to December 1995, 158 (53%) patients
showed an equivocal BS and 47 patients developed bone metastases. In the 158
patients with equivocal BS, prolonged clinical and imaging follow-up over 45
months (mean; range 12-120) was used to ascertain the presence or absence of bone
metastases. In these 158 patients the negative predictive value and positive
predictive value of the tumour marker panel to predict bone metastases was 97%
and 75% respectively. This study shows that in breast cancer patients the CEA-TPA
CA15.3 tumour marker panel has a high value in selecting those patients with bone
metastases, or at high risk of developing clinically-evident bone metastases,
among the large number of subjects with equivocal BS.
PMID- 10188889
TI - Randomized double-blind trial of beta-carotene and vitamin C in women with minor
cervical abnormalities.
AB - A double-blind, placebo-controlled, randomized, factorial study using a daily
oral administration of 30 mg beta-carotene and/or 500 mg vitamin C was conducted
in 141 women with colposcopically and histologically confirmed minor squamous
atypia or cervical intra-epithelial neoplasia (CIN) I. Over approximately 2 years
of follow-up, 43 lesions regressed to normal and 13 progressed to CIN II. The
regression rate was slightly higher, but not significantly so, in those
randomized to beta-carotene compared to no beta-carotene (hazard ratio = 1.58,
95% CI: 0.86-2.93, P = 0.14) and slightly lower, but not statistically
significant, for those randomized to vitamin C compared to no vitamin C (hazard
ratio = 0.65, 95% CI: 0.35-1.21, P = 0.17). In a model with no interaction, the
progression rate was slightly higher in those randomized to beta-carotene (hazard
ratio = 1.75, 95% CI: 0.57-5.36, P = 0.32) and also in those randomized to
vitamin C (hazard ratio = 2.40, 95% CI: 0.74-7.80, P = 0.13). Neither of these
were statistically significant. However, there was some evidence of an
interaction effect of the two compounds on the progression rate (P = 0.052), with
seven of the progressed lesions occurring in those randomized to both vitamins
compared to a total of six in the three other groups. The currently available
evidence from this and other trials suggests that high doses of these compounds
are unlikely to increase the regression or decrease the progression of minor
atypia and CIN I.
PMID- 10188890
TI - Phase I study of Carzelesin (U-80,244) given (4-weekly) by intravenous bolus
schedule.
AB - Carzelesin is a cyclopropylpyrroloindole analogue which acts as a DNA-sequence
specific alkylating agent. In this phase I study, Carzelesin was given as a 4
weekly 10 min i.v. infusion to 51 patients with advanced solid tumours. Patients
received a median of two courses (range 1-5) at one of nine dose levels: 24, 48,
96, 130, 150, 170, 210, 250 and 300 microg m(-2). According to NCI-CTC criteria,
non-haematological toxicities (grade 1/2) included fever, nausea and vomiting,
mucositis and anorexia, none of which was clearly dose related. The dose-limiting
toxicity was haematological and consisted mainly of neutropenia and to a lesser
extent thrombocytopenia. From the dose level 150 microg m(-2), the haematological
toxicity (particularly thrombocytopenia) was delayed in onset, prolonged and
cumulative in some patients. In several courses, double WBC nadirs occurred. The
maximum tolerated dose for a single course was 300 microg m(-2). From the dose
level 170 microg m(-2), the intended dose intensity could not be delivered to
most patients receiving > 2 courses owing to cumulative haematological toxicity.
The dose level with the best dose intensity for multiple courses was 150 microg
m(-2). The pharmacokinetics of Carzelesin and its metabolites (U-76,073; U
76,074) have been established in 31 patients during the first course of treatment
using a HPLC method. Carzelesin exhibited linear pharmacokinetics. The
concentration of U-76,074 (active metabolite) extended above the lower limit of
quantitation (1 ng ml(-1)) for short periods of time and only at the higher dose
levels. There was no relationship between neutropenia and the AUC of the prodrug
Carzelesin, but the presence of detectable plasma levels of the active metabolite
U-76,074 was usually associated with a substantial decrease in ANC values.
PMID- 10188891
TI - Phase I/II study of weekly irinotecan and concurrent radiation therapy for
locally advanced non-small cell lung cancer.
AB - A study was undertaken to determine the maximum tolerated dose, the dose-limiting
toxicities, and the response rate of irinotecan administered weekly with
concurrent thoracic radiation therapy in patients with locally advanced non-small
cell lung cancer. In a phase I/II clinical trial, patients with histologically
documented, surgically unresectable stage IIIA or IIIB non-small cell lung cancer
(NSCLC) were enrolled. Irinotecan was administered as a 90 min intravenous
infusion once weekly for 6 weeks. The starting dose was 30 mg m(-2) and dose
escalation was done in 15 mg m(-2) increments. Dose-limiting toxicity was defined
as grade 3 nonhaematologic toxicity (excluding nausea, vomiting and alopecia) or
grade 4 haematologic toxicity according to the WHO criteria. Radiation was
delivered to the primary tumour and regional lymph nodes (40 Gy), followed by a
boost to the primary tumour (20 Gy). Twenty-seven patients were entered into this
study at three irinotecan dose levels (30, 45 and 60 mg m(-2)). Twenty-six
eligible patients were evaluated for toxic effects and clinical outcome. Severe
oesophagitis, pneumonitis, and diarrhoea occurred at 45 and 60 mg m(-2). Three of
the five patients given 60 mg m(-2) developed grade 3 or 4 oesophagitis and
pneumonitis. In addition, one patient died of pneumonitis after completing
therapy at 45 mg m(-2) in the phase II study. The objective response rate was
76.9% (95% CI, 53.0-88.9%). Oesophagitis, pneumonitis, and diarrhoea are the dose
limiting toxicities of weekly irinotecan combined with thoracic irradiation. The
maximum tolerated dose and the dose for the phase II study were 60 and 45 mg m(
2) wk(-1), respectively. This combined therapy for locally advanced non-small
cell lung cancer is promising and shows acceptable toxicity.
PMID- 10188892
TI - Loss of heterozygosity at chromosome 1p in different solid human tumours:
association with survival.
AB - The distal half of chromosome 1p was analysed with 15 polymorphic microsatellite
markers in 683 human solid tumours at different locations. Loss of heterozygosity
(LOH) was observed at least at one site in 369 cases or 54% of the tumours. LOHs
detected ranged from 30-64%, depending on tumour location. The major results
regarding LOH at different tumour locations were as follows: stomach, 20/38
(53%); colon and rectum, 60/109 (55%); lung, 38/63 (60%); breast, 145/238 (61%);
endometrium, 18/25 (72%); ovary, 17/31 (55%); testis, 11/30 (37%); kidney, 22/73
(30%); thyroid, 4/14 (29%); and sarcomas, 9/14 (64%). High percentages of LOH
were seen in the 1p36.3, 1p36.1, 1p35-p34.3, 1p32 and 1p31 regions, suggesting
the presence of tumour-suppressor genes. All these regions on chromosome 1p show
high LOH in more than one tumour type. However, distinct patterns of LOH were
detected at different tumour locations. There was a significant separation of
survival curves, with and without LOH at chromosome 1p, in the breast cancer
patients. Multivariate analysis showed that LOH at 1p in breast tumours is a
better indicator for prognosis than the other variables tested in our model,
including nodal metastasis.
PMID- 10188893
TI - Characteristics of small breast and/or ovarian cancer families with germline
mutations in BRCA1 and BRCA2.
AB - For families with a small number of cases of breast and/or ovarian cancer,
limited data are available to predict the likelihood of genetic predisposition
due to mutations in BRCA1 or BRCA2. In 104 families with three or more affected
individuals (average 3.8) seeking counselling at family cancer clinics, mutation
analysis was performed in the open reading frame of BRCA1 and BRCA2 by the
protein truncation test and mutation-specific assays. In 31 of the 104 families
tested, mutations were detected (30%). The majority of these mutations (25)
occurred in BRCA1. Mutations were detected in 15 out of 25 families (60%) with
both breast and ovarian cancer and in 16 out of 79 families (20%) with
exclusively cases of breast cancer. Thus, an ovarian cancer case strongly
predicted finding a mutation (P < 0.001). Within the group of small breast-cancer
only families, a bilateral breast cancer case or a unilateral breast cancer case
diagnosed before age 40 independently predicted finding a BRCA1 or BRCA2 mutation
(P = 0.005 and P = 0.02, respectively). Therefore, even small breast/ovarian
cancer families with at least one case of ovarian cancer, bilateral breast
cancer, or a case of breast cancer diagnosed before age 40, should be referred
for mutation screening.
PMID- 10188894
TI - Fatigue in advanced cancer: a prospective controlled cross-sectional study.
AB - Uncontrolled studies have reported that fatigue is a common symptom among
patients with advanced cancer. It is also a frequent complaint among the general
population. Simply asking cancer patients whether or not they feel fatigued does
not distinguish between the 'background' level of this symptom in the community
and any 'excess' arising as a result of illness. The aim of this study was to
determine the prevalence of fatigue among palliative care inpatients in
comparison with a control group of age and sex-matched volunteers without cancer.
In addition, the correlates of fatigue were investigated. The prevalence of
'severe subjective fatigue' (defined as fatigue greater than that experienced by
95% of the control group) was found to be 75%. Patients were malnourished, had
diminished muscle function and were suffering from a number of physical and
mental symptoms. The severity of fatigue was unrelated to age, sex, diagnosis,
presence or site of metastases, anaemia, dose of opioid or steroid, any of the
haematological or biochemical indices (except urea), nutritional status,
voluntary muscle function, or mood. A multivariate analysis found that fatigue
severity was significantly associated with pain and dypnoea scores in the
patients, and with the symptoms of anxiety and depression in the controls. The
authors conclude that subjective fatigue is both prevalent and severe among
patients with advanced cancer. The causes of this symptom remain obscure. Further
work is required in order to determine if the associations reported between
fatigue and pain and between fatigue and dyspnoea are causal or coincidental.
PMID- 10188895
TI - Combination chemotherapy for choroidal melanoma: ex vivo sensitivity to
treosulfan with gemcitabine or cytosine arabinoside.
AB - Treatment of choroidal melanoma by chemotherapy is usually unsuccessful, with
response rates of less than 1% reported for dacarbazine (DTIC)-containing
regimens which show 20% or more response rates in skin melanoma. Recently, we
reported the activity of several cytotoxic agents against primary choroidal
melanoma in an ATP-based tumour chemosensitivity assay (ATP-TCA). In this study,
we have used the same method to examine the sensitivity of choroidal melanoma to
combinations suggested by our earlier study. Tumour material from 36 enucleated
eyes was tested against a battery of single agents and combinations which showed
some activity in the previous study. The combination of treosulfan with
gemcitabine or cytosine arabinoside showed consistent activity in 70% and 86% of
cases, respectively. Paclitaxel was also active, particularly in combination with
treosulfan (47%) or mitoxantrone (33%). Addition of paclitaxel to the combination
of treosulfan + cytosine analogue added little increased sensitivity. For
treosulfan + cytosine arabinoside, further sequence and timing experiments showed
that simultaneous administration gave the greatest suppression, with minor loss
of inhibition if the cytosine analogue was given 24 h after the treosulfan.
Administration of cytosine analogue 24 h before treosulfan produced considerably
less inhibition at any concentration. While we have so far been unable to study
metastatic tumour from choroidal melanoma patients, the combination of treosulfan
with gemcitabine or cytosine arabinoside shows activity ex vivo against primary
tumour tissue. Clinical trials are in progress.
PMID- 10188896
TI - Serum YKL-40 and colorectal cancer.
AB - YKL-40 is a mammalian member of the chitinase protein family. Although the
function of YKL-40 is unknown, the pattern of its expression suggests a function
in remodelling or degradation of extracellular matrix. High serum YKL-40 has been
found in patients with recurrent breast cancer and has been related to short
survival. In the present study we analysed YKL-40 in preoperative sera from
patients with colorectal cancer and evaluated its relation to survival. Serum YKL
40 was determined by RIA in 603 patients. Survival after operation was
registered, and median follow-up time was 61 months. Three hundred and forty
patients died. Sixteen per cent of the patients with Dukes' A, 26% with Dukes' B,
19% with Dukes' C and 39% with Dukes' D had high serum YKL-40 levels (adjusted
for age). Analysis of serum YKL-40 as a continuous variable showed an association
between increased serum YKL-40 and short survival (P < 0.0001). Patients with
high preoperative serum YKL-40 concentration had significantly shorter survival
than patients with normal YKL-40 (HR = 1.7; 95% CI: 1.3-2.1, P < 0.0001).
Multivariate Cox analysis including serum YKL-40, serum CEA, Dukes' stage, age
and gender showed that high YKL-40 was an independent prognostic variable for
short survival (HR = 1.4; 95% CI: 1.1-1.8, P = 0.007). These results suggest that
YKL-40 may play an important role in tumour invasion.
PMID- 10188898
TI - Competing risks analyses for recurrence from primary breast cancer.
AB - The effects of prognostic factors on local, regional or distant metastasis are
standardly assessed separately. Competing risks analyses may be used to assess
simultaneously the effects of factors on different types of first recurrence.
Data for a cohort of 678 primary invasive breast cancer patients accrued between
1971 and 1990, updated to 1995, included type of first recurrence (local,
regional, distant). We investigated the effects of the traditional factors of
age, tumour size, nodal status, ER, PgR, adjuvant therapy (hormones,
chemotherapy, radiotherapy) on type of recurrence and time to recurrence for all
patients and for those aged > or = 65. For all ages of patients, there were five
factors with significant associations with type or time to first recurrence.
Adjuvant radiation was the only factor which had an effect (P < or = 0.05) on the
type of first recurrence: being associated with a reduction in local recurrence.
Age, nodal status, tumour size and adjuvant chemotherapy all had significant
associations across all types of first recurrence, and in particular with time to
recurrence for both local and distant metastasis. This indicates a potential lack
of independence in these end-points. For patients > or = 65 years of age, there
were no factors which differentially affected type of recurrence, while only
nodal status and tumour size had significant associations with time to
recurrence. Analyses were used to assess simultaneously the effects of
traditional prognostic factors and treatment options on type of first recurrence
and time to first recurrence. The extension to evaluations with newer prognostic
factors would expedite the determination and mode of biologic activity for such
factors.
PMID- 10188897
TI - Stage III and oestrogen receptor negativity are associated with poor prognosis
after adjuvant high-dose therapy in high-risk breast cancer.
AB - We report on the efficacy and toxicity of a sequential high-dose therapy with
peripheral blood stem cell (PBSC) support in 85 patients with high-risk stage
II/III breast cancer. There were 71 patients with more than nine tumour-positive
axillary lymph nodes. An induction therapy of two cycles of ifosfamide (total
dose, 7.5 g m(-2)) and epirubicin (120 mg m(-2)) was given, and PBSC were
harvested during G-CSF-supported leucocyte recovery following the second cycle.
The PBSC-supported high-dose chemotherapy consisted of two cycles of ifosfamide
(total dose, 12,000 mg m(-2)), carboplatin (900 mg m(-2)) and epirubicin (180 mg
m(-2)). Patients were autografted with a median number of 3.7 x 10(6) CD34+ cells
kg(-1) (range, 1.9-26.5 x 10(6)) resulting in haematological reconstitution
within approximately 2 weeks following high-dose therapy. The toxicity was
moderate in general, and there was no treatment-related toxic death. Twenty-one
patients relapsed between 3 and 30 months following the last cycle of high-dose
therapy (median, 11 months). The probability of disease-free and overall survival
at 4 years were 60% and 83%, respectively. According to a multivariate analysis,
patients with stage II disease had a significantly better probability of disease
free survival (74%) in comparison to patients with stage III disease (36%). The
probability of disease-free survival was also significantly better for patients
with oestrogen receptor-positive tumours (70%) compared to patients with receptor
negative ones (40%). Bone marrow samples collected from 52 patients after high
dose therapy were examined to evaluate the prognostic relevance of isolated
tumour cells. The proportion of patients presenting with tumour cell-positive
samples did not change in comparison to that observed before high-dose therapy
(65% vs 71%), but a decrease in the incidence and concentration of tumour cells
was observed over time after high-dose therapy. This finding was true for
patients with relapse and for those in remission, which argues against a
prognostic significance of isolated tumour cells in bone marrow. In conclusion,
sequential high-dose chemotherapy with PBSC support can be safely administered to
patients with high-risk stage II/III breast cancer. Further intensification of
the therapy, including the addition of non-cross resistant drugs or immunological
approaches such as the use of antibodies against HER-2/NEU, may be envisaged for
patients with stage III disease and hormone receptor-negative tumours.
PMID- 10188899
TI - Pre-operative chemotherapy in early stage resectable non-small-cell lung cancer:
a randomized feasibility study justifying a multicentre phase III trial.
AB - Surgical resection offers the best chance for cure for early stage non-small-cell
lung cancer (NSCLC, stage I, II, IIIA), but the 5-year survival rates are only
moderate, with systemic relapse being the major cause of death. Pre-operative
(neo-adjuvant) chemotherapy has shown promise in small trials restricted to stage
IIIA patients. We believe similar trials are now appropriate in all stages of
operable lung cancer. A feasibility study was performed in 22 patients with early
stage (IB, II, IIIA) resectable NSCLC; randomized to either three cycles of
chemotherapy [mitomycin-C 8 mg m(-2), vinblastine 6 mg m(-2) and cisplatin 50 mg
m(-2) (MVP)] followed by surgery (n = 11), or to surgery alone. Of 40 eligible
patients, 22 agreed to participate (feasibility 55%) and all complied with the
full treatment schedule. All symptomatic patients achieved either complete (50%)
or partial (50%) relief of tumour-related symptoms with pre-operative
chemotherapy. Fifty-five per cent achieved objective tumour response, and a
further 27% minor tumour shrinkage; none had progressive disease. Partial
pathological response was seen in 50%. No severe (WHO grade III-IV) toxicities
occurred. No significant deterioration in quality of life was detected during
chemotherapy. Pre-operative MVP chemotherapy is feasible in early stage NSCLC,
and this study has now been initiated as a UK-wide Medical Research Council phase
III trial.
PMID- 10188900
TI - Elevated reticulocyte count--a clue to the diagnosis of haemolytic-uraemic
syndrome (HUS) associated with gemcitabine therapy for metastatic duodenal
papillary carcinoma: a case report.
AB - In adults, the haemolytic-uraemic syndrome (HUS) is associated with probable
causative factors in the minority of all cases. Cytotoxic drugs are one of these
potential causative agents. Although metastatic cancer by itself is a recognized
risk-factor for the development of HUS, therapy with mitomycin-C, with cis
platinum, and with bleomycin carries a significant, albeit extremely small, risk
for the development of HUS, compared with all other cytotoxic drugs. Gemcitabine
is a novel cytotoxic drug with promising activity against pancreatic
adenocarcinoma. We are reporting on one patient with metastatic duodenal
papillary carcinoma developing HUS while on weekly gemcitabine therapy. The
presenting features in this patient were non-cardiac pulmonary oedema, renal
failure, thrombocytopenia and haemolytic anaemia. The diagnosis of HUS was made
on the day of admission of the patient to this institution. Upon aggressive
therapy, including one single haemodialysis and five plasmaphereses, the patient
recovered uneventfully, with modestly elevated creatinine-values as a remnant of
the acute illness. Re-exposure to gemcitabine 6 months after the episode of HUS
instituted for progressive carcinoma, thus far has not caused another episode of
HUS.
PMID- 10188901
TI - Patient survival after D1 and D2 resections for gastric cancer: long-term results
of the MRC randomized surgical trial. Surgical Co-operative Group.
AB - Controversy still exists on the optimal surgical resection for potentially
curable gastric cancer. Much better long-term survival has been reported in
retrospective/non-randomized studies with D2 resections that involve a radical
extended regional lymphadenectomy than with the standard D1 resections. In this
paper we report the long-term survival of patients entered into a randomized
study, with follow-up to death or 3 years in 96% of patients and a median follow
up of 6.5 years. In this prospective trial D1 resection (removal of regional
perigastric nodes) was compared with D2 resection (extended lymphadenectomy to
include level 1 and 2 regional nodes). Central randomization followed a staging
laparotomy. Out of 737 patients with histologically proven gastric adenocarcinoma
registered, 337 patients were ineligible by staging laparotomy because of
advanced disease and 400 were randomized. The 5-year survival rates were 35% for
D1 resection and 33% for D2 resection (difference -2%, 95% CI = -12%-8%). There
was no difference in the overall 5-year survival between the two arms (HR = 1.10,
95% CI 0.87-1.39, where HR > 1 implies a survival benefit to D1 surgery).
Survival based on death from gastric cancer as the event was similar in the D1
and D2 groups (HR = 1.05, 95% CI 0.79-1.39) as was recurrence-free survival (HR =
1.03, 95% CI 0.82-1.29). In a multivariate analysis, clinical stages II and III,
old age, male sex and removal of spleen and pancreas were independently
associated with poor survival. These findings indicate that the classical
Japanese D2 resection offers no survival advantage over D1 surgery. However, the
possibility that D2 resection without pancreatico-splenectomy may be better than
standard D1 resection cannot be dismissed by the results of this trial.
PMID- 10188902
TI - The presentation and management of post-partum choriocarcinoma.
AB - Post-partum choriocarcinoma is a rare complication of pregnancy. We have analysed
a series of nine consecutive patients presenting with choriocarcinoma after a
full-term non-molar pregnancy. All patients were managed at the Supraregional
Trophoblastic Disease Screening and Treatment Centre at Weston Park Hospital,
Sheffield between 1987 and 1996. All presented with persistent primary or
secondary post-partum haemorrhage. Treatment with multiagent chemotherapy
(initially methotrexate, dactinomycin and etoposide) was successful in all cases.
Early diagnosis is important because this rare condition is potentially curable
with appropriate chemotherapy.
PMID- 10188903
TI - Comparison of immunohistochemistry with immunoassay (ELISA) for the detection of
components of the plasminogen activation system in human tumour tissue.
AB - Enzyme-linked immunosorbent assay (ELISA) methods and immunohistochemistry (IHC)
are techniques that provide information on protein expression in tissue samples.
Both methods have been used to investigate the impact of the plasminogen
activation (PA) system in cancer. In the present paper we first compared the
expression levels of uPA, tPA, PAI-1 and uPAR in a compound group consisting of
33 cancer lesions of various origin (breast, lung, colon, cervix and melanoma) as
quantitated by ELISA and semi-quantitated by IHC. Secondly, the same kind of
comparison was performed on a group of 23 melanoma lesions and a group of 28
breast carcinoma lesions. The two techniques were applied to adjacent parts of
the same frozen tissue sample, enabling the comparison of results obtained on
material of almost identical composition. Spearman correlation coefficients
between IHC results and ELISA results for uPA, tPA, PAI-1 and uPAR varied between
0.41 and 0.78, and were higher for the compound group and the breast cancer group
than for the melanoma group. Although a higher IHC score category was always
associated with an increased median ELISA value, there was an overlap of ELISA
values from different scoring classes. Hence, for the individual tumour cases the
relation between ELISA and IHC is ambiguous. This indicates that the two
techniques are not directly interchangeable and that their value for clinical
purposes may be different.
PMID- 10188904
TI - Mutation in the PTEN/MMAC1 gene in archival low grade and high grade gliomas.
AB - The PTEN gene, located on 10q23.3, has recently been described as a candidate
tumour suppressor gene that may be important in the development of advanced
cancers, including gliomas. We have investigated mutation in the PTEN gene by
direct sequence analysis of PCR products amplified from samples microdissected
from 19 low grade (WHO Grade I and II) and 27 high grade (WHO grade III and IV)
archival, formalin-fixed, paraffin-embedded gliomas. Eleven genetic variants in
ten tumours have been identified. Eight of these are DNA sequence changes that
could affect the encoded protein and were present in 0/2 pilocytic astrocytomas,
0/2 oligoastrocytomas, 0/1 oligodendroglioma, 0/14 astrocytomas, 3/13 (23%)
anaplastic astrocytomas and 5/14 (36%) glioblastomas. PTEN mutations were found
exclusively in high grade gliomas; this finding was statistically significant.
Only two of the PTEN genetic variants have been reported in other studies; two of
the genetic changes are in codons in which mutations have not been found
previously. The results of this study indicate that mutation in the PTEN gene is
present only in histologically more aggressive gliomas, may be associated with
the transition from low histological grade to anaplasia, but is absent from the
majority of high grade gliomas.
PMID- 10188905
TI - Discrimination of double primary lung cancer from intrapulmonary metastasis by
p53 gene mutation.
AB - When multiple synchronous lung tumours are identified, discrimination of
multicentric lung cancers from intrapulmonary metastases by clinical findings is
often difficult. We used genetic alterations in p53 gene as a discrimination
marker of double primary lung cancers from single lung cancer with intrapulmonary
metastasis. Twenty of 861 patients with primary lung cancer who underwent lung
resection were selected as subjects because they showed synchronous double solid
tumours of the same histological type in the unilateral lung without distant
metastases. In addition, they had been diagnosed as lung carcinoma with
intrapulmonary metastasis by clinical and histological findings. DNAs were
extracted from paraffin-embedded tissue of paired tumours from these 20 patients.
Exons 5-9 of the p53 gene were examined for genetic alterations in the tumours by
polymerase chain reaction, single-strand conformation polymorphism analysis and
subsequent DNA sequencing analysis. Three different patterns in the distribution
of p53 mutations in double lung tumours were observed: [A] mutation in only one
of the tumours (four cases), [B] different mutations in the tumours (two cases),
and [C] same mutation in both tumours (one case). The cases of [A] or [B]
patterns could be classified as double primary lung cancers, while the case of
the [C] pattern was suggested to be lung cancer with intrapulmonary metastasis.
These results suggested that the multicentric cancers were more frequent than the
intrapulmonary metastatic cancers in double cancer cases.
PMID- 10188906
TI - Prognostic significance of angiogenesis in human pancreatic cancer.
AB - To evaluate whether angiogenic factors are of clinical relevance to actual human
pancreatic cancers, we studied the intratumoral microvessel density (IMD), and PD
ECGF, VEGF protein expression in 40 pancreatic cancers using
immunohistochemistry. We also investigated PD-ECGF and VEGF gene expression using
reverse transcriptase-PCR (RT-PCR). Of the 40 pancreatic cancers studied, 30
carcinomas (75.0%) were evaluated to be PD-ECGF-positive and 10 carcinomas
(25.0%) were determined to be PD-ECGF-negative. In contrast, 27 carcinomas
(67.5%) were evaluated to be VEGF-positive, whereas 13 carcinomas (32.5%) were
VEGF-negative. VEGF gene expression was moderately associated with an increase in
the IMD (r2 = 0.181, P = 0.006), but no significant relationship was found
between PD-ECGF gene expression and the IMD (r2 = 0.093, P = 0.059). However,
tumours with positive expression for both PD-ECGF and VEGF had a higher IMD (P =
0.027). The results of the immunohistochemistry agreed well with the results of
the quantitative RT-PCR. The median survival time of the hypervascular group was
significantly shorter than that of the hypovascular group (P < 0.0001). In
comparing the survival according to PD-ECGF and VEGF gene expression, the median
survival time of the patients with positive PD-ECGF expression was significantly
shorter than those with negative PD-ECGF expression (P = 0.040). Furthermore, the
median survival time of the patients with positive VEGF expression was
significantly shorter than those with negative VEGF expression (P = 0.048).
However, the Cox multivariate analysis indicated that the IMD and VEGF expression
were independent prognostic factors of the various clinicopathologic variables in
pancreatic cancer patients (P = 0.0021 and P = 0.0443, respectively).
PMID- 10188907
TI - Absence of progesterone receptor associated with secondary breast cancer in
postmenopausal women.
AB - The relationship between expression of receptors for oestrogen and progesterone
(ER and PR) and disease progression in breast cancer was investigated by
comparing immunocytochemical determinations of ER and PR in fine needle aspirates
from primary and secondary breast tumours. Rates of receptor expression were
significantly higher in primary than in secondary lesions: for ER 63.3% (n = 689)
compared with 45.3% (n = 223), and for PR 53.7% (n = 443) compared with 33.1% (n
= 121). The effect of menopausal status was examined by subdividing the patient
cohort into those over or under the age of 50 years. In both instances, ER
expression in secondary tumours was relatively low; however, only postmenopausal
patients had significantly lower rates of PR expression in secondary tumours.
Consistent with this, an increase in the ER+PR- profile in secondary tumours
compared with primary cases from postmenopausal patients was seen, and in a
multivariate analysis, a specific absence of PR expression in secondary tumours
was revealed. Comparison of ER and PR expression in simultaneously sampled
primary tumours and lymph node metastases from the same patient showed that
receptor expression was stable with progression to a metastatic site as results
were concordant for ER in 92% (n = 88) and PR in 93.8% of cases (n = 65). These
results suggest that absence of PR expression in primary breast cancer is
associated with disease progression and may be a marker of an aggressive tumour
phenotype.
PMID- 10188908
TI - Prognostic role of p27Kip1 and apoptosis in human breast cancer.
AB - Human breast carcinoma is biologically heterogeneous, and its clinical course may
vary from an indolent slowly progressive one to a course associated with rapid
progression and metastatic spread. It is important to establish prognostic
factors which will define subgroups of patients with low vs high risk of
recurrence so as to better define the need for additional therapy. Additional
characterization of the molecular make-up of breast cancer phenotypes should
provide important insights into the biology of breast cancer. In the present
study, we investigated apoptosis, expression of p27Kip1 and p53 retrospectively
in 181 human breast cancer specimens. In addition, their relevance to the
biological behaviour of breast cancer was examined. Our studies found a
significant association among high histological grade, high p53, low apoptosis
and low p27. Our results also demonstrated that, in human breast cancer, low
levels of p27 and apoptotic index (AI) strongly correlated with the presence of
lymph node metastasis and decreased patient survival. In node-negative patients,
however, p27 also had prognostic value for relapse-free and overall survival in
multivariate analysis. Furthermore p27 and AI had predictive value for the
benefits of chemotherapy. These latter observations should prompt prospective
randomized studies designed to investigate the predictive role of p27 and AI in
determining who should receive chemotherapy in node-negative patients.
PMID- 10188909
TI - Expression of somatostatin receptors in oncocytic (Hurthle cell) neoplasia of the
thyroid.
AB - Ten consecutive patients with Hurthle cell lesions of the thyroid
(nodule/adenoma/carcinoma) were studied by (111)In-DTPA-D-Phe1-octreotide
scintigraphy. Octreotide scintigraphy localized the primary Hurthle cell tumour
in eight patients as distinct areas of increased uptake of radionuclide. Two
patients with Hurthle cell carcinoma, previously thyroidectomized, had their
metastases visualized by octreotide scintigraphy. Northern analyses showed
expression of multiple somatostain receptor subtypes. Visualization of the
Hurthle cell tumour may be due to a higher expression of somatostatin receptors
in the lesions than in surrounding normal thyroid tissue. The tissue/blood
(111)In concentration ratios for tumour samples from five patients showed clearly
higher values than observed for normal connective tissue, muscle or lymph nodes.
A relatively high uptake of (111)In was also observed in goiter tissue, which may
lead to misinterpretations. The main indication for octreotide scintigraphy in
patients with Hurthle cell carcinoma is suspicion of metastatic disease.
PMID- 10188910
TI - Measurement of prostate-specific antigen in detection of benign or malignant
breast disease in women.
AB - Using a highly sensitive chemiluminescent enzyme immunoassay, we have evaluated
the measurement of serum prostate-specific antigen (PSA) as a potential
diagnostic test for differentiation between women with breast cancer and those
with benign breast disease. In a controlled study consisting of 284 women with
well-documented patient files and matched for age and long-term place of
residence, serum samples collected from 90 women with histologically confirmed
breast cancer, 94 women with benign breast disease and 100 controls were
analysed. Serum total PSA levels in benign breast disease and cancer patients are
not statistically different from those of healthy controls. Total PSA levels
decrease with age in normal controls and breast cancer patients but not in those
with benign breast disease. The total PSA concentration decreases after menopause
in healthy women, though not in patients with breast cancer or benign breast
disease. Total PSA bore no relation to the histological type or grade of the
tumour or the disease stage of the breast cancer patients. In benign breast
disease, all mastopathy patients had normal total PSA, whereas elevation of the
values was observed in 7% of fibroadenoma patients. Our results show that serum
total PSA cannot be used to distinguish between healthy women and/or women with
breast cancer or benign breast disease.
PMID- 10188911
TI - Increased transcriptional activity of prostate-specific antigen in the presence
of TNP-470, an angiogenesis inhibitor.
AB - Prostate-specific antigen, PSA, is regarded as a reliable surrogate marker for
androgen-independent prostate cancer (AIPC). Concern has been raised that
investigational agents may affect PSA secretion without altering tumour growth or
volume. In a phase I trial, several patients with AIPC had elevated serum PSA
levels while receiving TNP-470 that reversed upon discontinuation. TNP-470
inhibits capillary growth in several angiogenesis models. These observations
prompted us to determine if TNP-470, or its metabolite, AGM-1883, altered PSA
secretion. Intracellular protein and transcriptional levels of PSA and androgen
receptor were also determined. The highest TNP-470 concentration produced a 40.6%
decrease in cell number; AGM-1883 had minimal effects on cell viability. PSA
secretion per cell was induced 1.1- to 1.5-fold following TNP-470 exposure. The
same trend was observed for AGM-1883. PSA and AR were transcriptionally up
regulated within 30 min after exposure to TNP-470. PSA transcription was
increased 1.4-fold, while androgen receptor (AR) transcription was induced 1.2
fold. The increased PSA transcriptional activity accounts for the increased PSA
secretion. Increased AR transcription was also reflected at the protein level. In
conclusion, TNP-470 and AGM-1883 both up-regulated PSA making clinical
utilization of this surrogate marker problematic.
PMID- 10188912
TI - The promoter and the enhancer region of the KLK 3 (prostate specific antigen)
gene is frequently mutated in breast tumours and in breast carcinoma cell lines.
AB - KLK3 or prostate specific antigen (PSA) is a serine protease, which is an
established tumour marker of prostatic adenocarcinoma. PSA is now used widely for
the diagnosis and monitoring of patients with prostate cancer. Recent studies
have demonstrated that about 70% of breast cancers produce PSA. In this study, we
examined the molecular mechanism underlying the expression of the PSA gene in
breast cancer and breast cancer cell lines. We analysed nine breast tumours
categorized on the basis of high- or low-PSA expression in tumour cytosols and
four breast cancer cell lines. To determine abnormalities associated with PSA
expression in breast tumours, genomic DNA was extracted and all five exons of the
PSA gene were polymerase chain reaction (PCR) amplified and sequenced on both
strands. PCR amplification was also performed for the promoter and enhancer
elements of the PSA gene. No mutations were observed in the coding portion of the
gene. A polymorphism was observed in exon 2 from three breast tumours. However,
sequencing of the promoter and the enhancer elements of the PSA gene reveals
several point mutations. Within a 5.8-kb promoter/enhancer region of the PSA
gene, we detected 16 different mutational hotspots (appearing more than once in
the nine tumours). Among these hotspots, two appeared in seven out of nine
tumours. Most importantly, the androgen response element (ARE I) in the proximal
promoter was found mutated in four tumours and in the breast carcinoma cell line
MCF-7. Mutations associated with the ARE I have been shown previously to result
in an 80% decrease in PSA gene expression. The mutations in the core enhancer and
promoter region probably contribute to the aberrant expression of the PSA gene in
breast tumours, possibly by altering the regulation of the gene by steroid
hormones.
PMID- 10188913
TI - Optimum porphyrin accumulation in epithelial skin tumours and psoriatic lesions
after topical application of delta-aminolaevulinic acid.
AB - Photodynamic therapy with topically applied delta-aminolaevulinic acid is used to
treat skin tumours by employing endogenously formed porphyrins as
photosensitizers. This study examines the time course of porphyrin metabolite
formation after topical application of delta-aminolaevulinic acid. Porphyrin
biosynthesis in human skin tumours (basal cell carcinoma, squamous cell
carcinoma), in psoriatic lesions, and in normal skin was investigated. Skin areas
were treated with delta-aminolaevulinic acid, and levels of total porphyrins,
porphyrin metabolites and proteins were measured in samples excised after 1, 2,
4, 6, 9, 12 and 24 h. There was an increase in porphyrin biosynthesis in all
tissues with maximum porphyrin levels in tumours between 2 and 6 h and in
psoriatic lesions 6 h after treatment. The pattern of porphyrins showed no
significant difference between normal and neoplastic skin, protoporphyrin being
the predominant metabolite. The results suggest that optimum irradiation time for
superficial epithelial skin tumours may be as soon as 2 h after application of
delta-aminolaevulinic acid, whereas for treatment of psoriatic lesions an
application time of 6 h is more suitable.
PMID- 10188914
TI - Inducible nitric oxide synthase (iNOS) expression may predict distant metastasis
in human melanoma.
AB - Expression of inducible nitric oxide synthase (iNOS) and its cellular
localization was investigated in subcutaneous or lymph node metastases of human
melanoma. Immunohistochemistry revealed that iNOS expression was limited to
melanoma cells. In samples of patients without distant metastases, the number of
iNOS+ tumour cells/total tumour cells was 55% +/- 17% (n = 12) compared with 9%
+/- 8% when distant metastases of lung, liver or brain occurred within an
observation period of 3 years (n = 10) (P < 0.001). Western blotting confirmed
the expression of iNOS protein in select cases. Notably, iNOS is expressed in
regional melanoma metastases and its expression is inversely related to the
tumour's metastatic potential. Thus, iNOS expression may have predictive value
for the development of distant metastases of human melanoma.
PMID- 10188916
TI - Induction of cachexia in mice.
PMID- 10188915
TI - Spectral morphometric characterization of breast carcinoma cells.
AB - The spectral morphometric characteristics of standard haematoxylin and eosin
breast carcinoma specimens were evaluated by light microscopy combined with a
spectral imaging system. Light intensity at each wavelength in the range of 450
800 nm was recorded for 10(4) pixels from each field and represented as
transmitted light spectra. A library of six characteristic spectra served to scan
the cells and reconstruct new images depicting the nuclear area occupied by each
spectrum. Fifteen cases of infiltrating ductal carcinoma and six cases of lobular
carcinoma were examined; nine of the infiltrating ductal carcinoma and three of
the lobular carcinoma showed an in situ component. The spectral morphometric
analysis revealed a correlation between specific patterns of spectra and
different groups of breast carcinoma cells. The most consistent result was that
lobular carcinoma cells of in situ and infiltrating components from all patients
showed a similar spectral pattern, whereas ductal carcinoma cells displayed
spectral variety. Comparison of the in situ and the infiltrating ductal solid,
cribriform and comedo carcinoma cells from the same patient revealed a strong
similarity of the spectral elements and their relative distribution in the
nucleus. The spectrum designated as number 5 in the library incorporated more
than 40% of the nuclear area in 74.08% of the infiltrating lobular cells and in
13.64% of the infiltrating ductal carcinoma cells (P < 0.001). Spectrum number 2
appeared in all infiltrating ductal cells examined and in none of the lobular
cells. These results indicate that spectrum number 5 is related to infiltrating
lobular carcinoma, whereas spectrum number 2 is characteristic for infiltrating
ductal carcinoma cells. Spectral similarity mapping of central necrotic regions
of comedo type in situ carcinoma revealed nuclear fragmentation into defined
segments composed of highly condensed chromatin. We conclude that the spectral
morphometric features found for lobular and ductal cell populations may serve
future automated histological diagnostics.
PMID- 10188917
TI - The effect of three week tamoxifen treatment on oestrogen receptor levels in
primary breast tumours: a flow cytometric study.
PMID- 10188918
TI - Involvement of radon levels in lung cancer.
PMID- 10188919
TI - Measurement of extravascular drug diffusion in multicellular layers.
PMID- 10188920
TI - Seasonal variations in the presentation and growth of thyroid cancer.
PMID- 10188921
TI - Live cell imaging.
PMID- 10188922
TI - Fluorescent probes for living cells.
AB - The functional characteristics of fluorescent probes used for imaging and
measuring dynamic processes in living cells are reviewed. Initial consideration
is given to general design requirements for delivery, targeting, detectability
and fluorescence readout, and current technologies for attaining them. Discussion
then proceeds to the more application-specific properties of intracellular ion
indicators, membrane potential sensors, probes for proteins and lipids, and cell
viability markers.
PMID- 10188923
TI - Visualization of neuronal form and function in brain slices by infrared
videomicroscopy.
AB - As a standard preparation for neurophysiological experiments, brain slices were
introduced some 20 years ago. Although this technique has greatly advanced our
understanding of brain physiology, the utility of this preparation has been
limited to some extent by the difficulty of visualizing individual neurons in
standard thick slices. The use of infrared videomicroscopy has solved this
problem. It is now possible to visualize neurons in slices in great detail, and
neuronal processes can be patch-clamped under visual control. Infrared
videomicroscopy has also been applied successfully to other fields of
neuroscience, such as neuronal development and neurotoxicity. A further
development of infrared videomicroscopy allows the visualization of the spread of
excitation in slices, making the technique a tool for investigating neuronal
function and the pharmacology of synaptic transmission.
PMID- 10188924
TI - Monitoring activity in neuronal populations with single-cell resolution in a
behaving vertebrate.
AB - Vertebrate behaviours are produced by activity in populations of neurons, but the
techniques typically used to study activity allow only one or very few nerve
cells to be monitored at a time. This limitation has prompted the development of
methods of imaging activity in the nervous system. The overall goal of these
methods is to image neural activity non-invasively in populations of neurons,
ideally with high spatial and temporal resolution. We have moved closer to this
goal by using confocal calcium imaging to monitor neural activity in the
transparent larvae of zebrafish. Neurons were labelled either by backfilling from
injections of the calcium indicator (Calcium Green dextran) into muscle or spinal
cord of larvae or by injections into blastomeres early in development. The
labelled neurons were bright enough at resting calcium levels to allow the
identification of individual neurons in the live, intact fish, based upon their
dendritic and axonal morphology. The neurons from the live animal could also be
reconstructed in three dimensions for morphometric study. Neurons increased their
fluorescence during activity produced by direct electrical stimulation and during
escape behaviours elicited by an abrupt touch to the head or tail of the fish.
The rise in calcium associated with a single action potential could be detected
as an increase in fluorescence of at least 7-10%, but neurons typically showed
much larger increases during behaviour. Calcium signals in the dendrites, soma
and nucleus could be resolved, especially when using the line-scanning mode,
which provides 2-ms temporal resolution. The imaging was used to study activity
in populations of motoneurons and hindbrain neurons during the escape behaviour
fish use to avoid predators. We found a massive activation of the motoneuron pool
and a differential activation of populations of hindbrain neurons during escapes.
The latter finding confirms predictions that the activity pattern of hindbrain
neurons may help to determine the directionality of the escape. This approach
should prove useful for studying the activity of populations of neurons
throughout the nervous system in both normal and mutant lines of fish.
PMID- 10188925
TI - Voltage-sensitive dyes for monitoring multineuronal activity in the intact
central nervous system.
AB - Optical monitoring of activity provides new kinds of information about brain
function. Two examples are discussed in this article. First, the spike activity
of many individual neurons in small ganglia can be determined. Second, the
spatiotemporal characteristics of coherent activity in the brain can be directly
measured. This article discusses both general characteristics of optical
measurements (sources of noise) as well as more methodological aspects related to
voltage-sensitive dye measurements from the nervous system.
PMID- 10188926
TI - Fluorescence microscopy of calcium and synaptic vesicle dynamics during synapse
formation in tissue culture.
AB - The signal transduction process involved in the development of the nerve terminal
is an intriguing question in developmental neurobiology. During the formation of
the neuromuscular junction, presynaptic development is induced by growth cone's
contact with the target muscle cell. Fluorescence microscopy with specific
markers has made it possible to follow signalling events during this process. By
using fluorescent calcium indicators, such as fura-2 and fluo-3, we found that a
rise in intracellular calcium is elicited in the growth cone upon its contact
with a target, and this calcium signal can also be elicited by local application
of basic fibroblast growth factor. To monitor the clustering of synaptic vesicles
in response to target contact, the fluorescent vesicular probe FMl-43 was used.
With this probe, we observed that packets of synaptic vesicle are already present
along the length of naive neurite, which has not encountered its synaptic target.
The activity-dependent loading of FMl-43 indicates that these packets can undergo
exocytosis and endocytosis upon depolarization. Time-lapse recording showed that
these packets are quite mobile. Upon target contact, synaptic vesicles become
clustered and immobilized at the contact site. The methodology and
instrumentation used in these studies are described in this article.
PMID- 10188927
TI - Fast optical measurement of membrane potential changes at multiple sites on an
individual nerve cell.
AB - In the past 15 years, there has been renewed interest in the detailed spatial
analyses of signalling in individual neurons. The behaviour of many nerve cells
is difficult to understand on the basis of microelectrode measurements from the
soma. Regional electrical properties of neurons have been studied using sharp
microelectrode and patch-electrode recordings from neuronal processes, high
resolution multisite optical recordings of Ca2+ concentration changes and by
using models to predict the distribution of membrane potential in the entire
neuronal arborization. Additional, direct evidence about electrical signalling in
neuronal processes of individual cells in situ can now be obtained by recording
of membrane potential changes using voltage-sensitive dyes. A number of recent
studies have shown that active regional electrical properties of individual
neurons are extraordinarily complex, dynamic and, in the general case, impossible
to predict by present models. This places a great significance on measuring
capabilities in experiments studying the detailed functional organization of
individual neurons. The main difficulty in obtaining a more accurate description
was that experimental techniques for studying regional electrical properties of
neurons were not available. With this motivation, we worked on the development of
multisite voltage-sensitive dye recording as a potentially powerful approach. The
results described here demonstrate that the sensitivity of voltage-sensitive dye
recording from branches of individual neurons was brought to a level at which it
can be used routinely in physiologically relevant experiments. The crucial figure
of-merit in this approach, the signal-to-noise ratio from neuronal processes in
intact ganglia, has been improved by a factor of roughly 150 over previously
available signals. The improvement in the sensitivity allowed, for the first
time, direct investigation of several important aspects of the functional
organization of an individual neuron: (1) the direction and the velocity of
action potential propagation in different neuronal processes in the neuropile was
determined; and (2) the interaction of two independent action potentials (spike
collision) was monitored directly in a neurite in the neuropile; (3) it was
demonstrated that several action potentials are initiated in the same neuron at
different sites (multiple spike trigger zones) by a single stimulus; (4) the
exact location and the size of one of the remote spike trigger zones was
determined; (5) the spread of passive subthreshold signals was followed in the
neurites in the neuropile. This kind of information was not previously available.
Preliminary experiments on vertebrate neurons indicate partial success in the
effort to use intracellularly applied voltage-sensitive dyes to record from
neurons in a mammalian brain slice preparation. The results suggest that, with
further improvements, it may be possible to follow optically synaptic integration
and spike conduction in the dendrites of vertebrate nerve cells. The main impact
of these results is a demonstration of a new way of analysing how individual
neurons are functionally organized. Limitations and prospects for the further
refinement of the technique are discussed mostly in terms of the signal-to-noise
ratio; both improvements in the apparatus and design of more sensitive dyes are
addressed.
PMID- 10188928
TI - Calcium imaging and multielectrode recordings of global patterns of activity in
the developing nervous system.
AB - Complex but coordinated interactions involving ensembles of neuronal cells result
in the accurate processing of information in the adult central nervous system.
However, recent studies monitoring the global patterns of activity of neuronal
populations have demonstrated that immature neurons also interact to produce
coordinated patterns of activity during the early stages of development. In
particular, these patterns of coordinated activity occur during the period when
neuronal connections are established, thus leading us to believe that such
activity patterns might underlie the precision to which many neural pathways are
wired up. Multielectrode recording and calcium imaging are two of the techniques
that have been instrumental in revealing the spatial and temporal properties of
the coordinated activity of developing neural networks in vitro. While
multielectrode arrays measure the action potential activity of the cells, calcium
imaging permits changes in intracellular calcium levels to be monitored over
time. Both techniques have been used successfully to monitor the activity of
cellular networks in culture, but they have also been applied in assessing the
patterns of activity in intact or semi-intact pieces of neural tissues, such as
the developing retina, neocortex and spinal cord. More recently, it has also been
possible to correlate the structure and function of the cellular components of
the networks by combining intracellular dye filling with the multineuronal
recordings. In this review, brief descriptions and the applications of the two
techniques will be presented, and the advantages and limitations of
multielectrode array will be compared with that of calcium imaging using
recordings of the developing mammalian retina as the primary example.
PMID- 10188929
TI - Age-related cognitive deficits, impaired long-term potentiation and reduction in
synaptic marker density in mice lacking the beta-amyloid precursor protein.
AB - Mutations in the beta-amyloid precursor protein are strongly associated with some
cases of familial Alzheimer's disease. The normal physiological role of beta
amyloid precursor protein in the brain was evaluated in a cross-sectional
analysis of mice deficient in beta-amyloid precursor protein. Compared with wild
type control mice the beta-amyloid precursor protein-null mice developed age
dependent deficits in cognitive function and also had impairments in long-term
potentiation. In addition, the brains of the beta-amyloid precursor protein-null
mice had marked reactive gliosis in many areas, especially in the cortex and
hippocampus. A subpopulation of mice (n = 15) died prematurely (between three and
18 months of age). Analysis of another six mice from the same population that
were showing weight loss and hypolocomotor activity exhibited a marked reactive
gliosis as detected by immunoreactivity for glial fibrillary acidic protein and a
profound loss of immunoreactivities for the presynaptic terminal vesicle marker
proteins synaptophysin and synapsin and the dendritic marker microtubule
associated protein-2 in many brain areas, but most predominantly in the cortex
and hippocampus. These results suggest that normal beta-amyloid precursor protein
may serve an essential role in the maintenance of synaptic function during
ageing. A compromise of this function of the beta-amyloid precursor protein may
contribute to the progression of the memory decline and the neurodegenerative
changes seen in Alzheimer's disease.
PMID- 10188930
TI - The role of the protein glycosylation state in the control of cellular transport
of the amyloid beta precursor protein.
AB - The amyloid beta precursor protein can exist as both a membrane-bound and a
secreted protein, with the former having the potential to generate the amyloid
beta peptide present in the neuritic plaques which are characteristic of
Alzheimer's disease. In this study, we have used a clone of the AtT20 mouse
pituitary cell line which expresses high levels of the amyloid beta precursor
protein to characterize the glycosylation state of the secreted and membrane
bound forms of the protein and to examine the role of post-translational
modifications in protein processing. Lectin blot analysis of immunoprecipitated
amyloid beta precursor protein demonstrated that the soluble form of the protein
contains significant amounts of sialic acid, with the lectin staining being
reduced in the particulate cellular fractions. Treatment of the cells with
mannosidase inhibitors to interfere with the formation of complex-type N-linked
glycans resulted in a decrease in secreted amyloid beta precursor protein and an
increase in the level of the cellular form of the protein. The increase in
amyloid beta precursor protein levels in the cellular fraction was accompanied by
an increase in perinuclear staining. Furthermore, cells overexpressing the
alpha2,6(N)-sialyltransferase enzyme also demonstrated an increase in amyloid
beta precursor protein secretion. These results suggest that the presence of
terminal sialic acid residues on complex-type N-glycans may be required for the
optimal transport of the amyloid beta precursor protein from the Golgi to the
cell membrane with the subsequent cleavage to generate the secreted form of the
protein.
PMID- 10188931
TI - Regional distribution of presenilin-1 messenger RNA in the embryonic rat brain:
comparison with beta-amyloid precursor protein messenger RNA localization.
AB - The messenger RNA expression of presenilin-1, an important gene responsible for
early-onset familial Alzheimer's disease, was investigated in the embryonic rat
brain with in situ hybridization histochemistry using an oligonucleotide probe
specific to the messenger RNA. It was also compared with that of beta-amyloid
precursor protein messenger RNA. Presenilin-1 and beta-amyloid precursor protein
messenger RNA were abundantly expressed throughout the central nervous system in
the embryonic day 13, 17 and 20 rat brain. Presenilin-1 messenger RNA was
strongly expressed in both neuroepithelium and differentiating fields. In
contrast, beta-amyloid precursor protein messenger RNA was preferentially
expressed in differentiating fields, while low expression of beta-amyloid
precursor protein messenger RNA was seen in neuroepithelium. Although the
expression patterns of these two messenger RNAs were basically similar, there
seemed to be a tendency that presenilin-1 messenger RNA was preferentially
expressed in immature neurons, while beta-amyloid precursor protein messenger RNA
was preferentially expressed in mature neurons, suggesting that presenilin-1 is
expressed earlier than beta-amyloid precursor protein and that presenilin-1 is
involved in beta-amyloid precursor protein processing. These data raise the
possibility that presenilin-1 and beta-amyloid precursor protein co-operatively
play pivotal roles in rat neurogenesis.
PMID- 10188932
TI - Differential induction of c-Fos, c-Jun and Jun B in the rat central nervous
system following unilateral entorhinal cortex lesion.
AB - In order to identify some of the molecular mechanisms that occur after a central
nervous system trauma, the immediate early gene encoded proteins c-Fos, c-Jun and
Jun B were analysed by immunocytochemistry following unilateral entorhinal cortex
lesion (controls, 30 min, 2, 5, 12 and 24 h, two, six, 10 and 14 days, four weeks
and six months postlesion). In the dentate gyrus, c-Fos was induced in some
supragranular neurons (30 min), massively expressed in granule cells
ipsilaterally to the lesion (2 h), expressed in hilar neurons (5 h and two days)
and was absent at all later stages. A basal expression of c-Jun was found in
dentate granule cells of controls, which was strongly increased on the lesion
side (2 h) and on the side contralateral to the lesion (12 h). c-Jun expression
returned to control levels by 24 h. Jun B was induced in granule cells
ipsilateral to the lesion within 2 h and was back to control levels by 5 h. In
the lateral septal area, c-Fos and c-Jun were induced 30 min postlesion and
decreased rapidly thereafter. In the cerebral cortex, a widespread induction of c
Fos and c-Jun occurred within 30 min after entorhinal cortex lesion and this up
regulation lasted until two days postlesion. These data indicate that
electrolytic lesion of the entorhinal cortex leads to a rapid and widespread
induction of c-Fos, c-Jun and Jun B. Within the denervated fascia dentata, some
of these changes may be linked to the reorganization processes following the
lesion. Alternatively, the alterations in immediate early gene expression
reported here may be due to changes in synaptic activity or postlesional seizures
which occur in this lesioning paradigm.
PMID- 10188933
TI - Two modes of corticospinal reinnervation occur close to spinal targets following
unilateral lesion of the motor cortex in neonatal hamsters.
AB - Although it has been shown that unilateral neonatal cortical ablation induces
bilateral corticospinal projections, the explanation for the pathways responsible
for this bilateral innervation remains controversial. We hypothesized that such
reinnervation may be supplied from newly formed fibers sprouting at the level
rostral to, or at, or caudal to the pyramidal decussation. In order to test our
hypothesis, we examined the brain and spinal cord of young hamsters which had a
unilateral ablation of the right motor cortex at six days postnatally, and then
received an injection of an anterograde neuronal lectin tracer, Phaseolus
vulgaris-leucoagglutinin, into the hindlimb area of the left motor cortex at 21
days postnatally. For the identification of motoneurons in the lumbar spinal
cord, some of these animals also received an injection of cholera toxin subunit
B, a retrograde tracer, into the gastrocnemius muscle. A quantitative analysis in
the left gray matter of the lumbar spinal cord indicated that the lectin labeling
was two to eight times higher in cortically ablated animals than in intact
animals. Immunohistochemical detection of the lectin revealed that innervation of
the left spinal cord occurred close to targets at lower levels in the spinal
cord. Two modes of reinnervation (types I and II) by the intact corticospinal
tract were recognized. The type I fibers consisted of recrossing axon collaterals
sprouted from the intact dorsal funiculus near their targets, while the type II
fibers were recrossing parent axons which entered the intact, right gray matter
several levels rostral to their targets, and then changed direction toward the
targets. The recrossing at lower spinal levels yielded a large number of
ipsilaterally labeled axons and their terminals in the gray matter of the
denervated lumbar cord, with a distribution pattern similar to that seen on the
intact side. The present results indicate that such ipsilateral innervation may
play an important role in the sparing and recovery of function following neonatal
hemicortical injury.
PMID- 10188934
TI - Dopamine receptor coupling to adenylyl cyclase in rat olfactory pathway: a
combined pharmacological-radioautographic approach.
AB - Dopamine binding sites of D1 and D2/D3 subtypes had been detected in the rat
peripheral olfactory system and postulated to account for dopamine-dependent
enhancement of olfactory memory and retro-inhibition of olfactory input within
the olfactory bulb, respectively. We further assessed, in the present study, the
mechanisms of these dopamine actions by using adenylyl cyclase activity assay and
[35S]GTP radioautography in rat olfactory bulb and mucosa. The D1 agonist SKF
38393 increased adenylyl cyclase activity on membranes of the olfactory bulb, but
not on those of the olfactory mucosa. Stimulation of adenylyl cyclase by SKF
38393 in the olfactory bulb was dose dependent, with a half-maximal effect (EC50)
at 0.16 microM SKF 38393, reaching 40% over basal adenylyl cyclase activity, and
was blocked by the D1 antagonist SCH 23390. The D2 agonists bromocriptine and
quinpirole inhibited both basal and forskolin-stimulated adenylyl cyclase
activities in the olfactory bulb and mucosa. These adenylyl cyclase inhibitions
were dose dependent, with EC50 values of 0.1-0.3 microM for bromocriptine and 1-3
microM for quinpirole, equal to 25% of basal enzyme activity at concentrations of
1-10 microM, and were blocked by the D2 antagonist eticlopride. The D2 antagonist
was devoid of any effect on basal and forskolin-stimulated adenylyl cyclase
activities in the olfactory bulb and mucosa. Odorant-induced stimulation of
adenylyl cyclase was blocked by D2 agonist in olfactory mucosa membranes, which
suggests dopaminergic regulation of odor detection in the olfactory mucosa. By
using microdissected fractions of the olfactory mucosa, D2 agonist-induced
inhibition of adenylyl cyclase was shown to occur only in lamina propria, thus co
localizing with D2 binding sites. [35S]GTP radioautography on tissue sections
revealed D2 agonist-induced G-protein activation in olfactory nerve and
glomerular layers of the olfactory bulb, and in the chorion of the olfactory
mucosa. Taken together, these data demonstrate functional coupling of the
dopamine receptors with adenylyl cyclase in both the olfactory bulb and mucosa,
and document novel aspects of dopamine's physiological involvement in olfaction
and of D2-mediated signal transduction.
PMID- 10188935
TI - Dizocilpine maleate, MK-801, but not 2,3-dihydroxy-6-nitro-7-sulfamoyl
benzo(f)quinoxaline, NBQX, prevents transneuronal degeneration of nigral neurons
after neurotoxic striatal-pallidal lesion.
AB - Unilateral neurotoxin lesion of rat caudate-putamen and globus pallidus resulted
in delayed, transneuronal degeneration of GABAergic substantia nigra pars
reticulata neurons. To explore whether the disinhibition of endogenous glutamate
excitatory input played a role in the degeneration of substantia nigra pars
reticulata neurons, animals with unilateral striatal-pallidal lesions received
three daily intraperitoneal injections of either dizocilpine maleate (MK-801, 1
or 10 mg/kg), an N-methyl-D-aspartate glutamate receptor blocker, or 2,3
dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX, 30 mg/kg), an alpha
amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor blocker, that began 24 h
after the striatal-pallidal neurotoxin lesion. Drug treatment affected neither
the volume of the initial lesion nor the volume of striatal-pallidal glial
fibrillary acidic protein immunoreactivity. Neuron number in the substantia nigra
pars reticulata ipsilateral to the lesioned striatopallidum was reduced on
average by 37% in untreated control rats, in low dose MK-801, and NBQX-treated
rats (P<0.0001). However, in animals treated with high doses of MK-801 there was
no difference in the number of neurons in the substantia nigra pars reticulata
ipsilateral or contralateral to the neurotoxin lesion. These data demonstrate
that dose-related treatment with N-methyl-D-aspartate glutamate receptor blockers
protects substantia nigra pars reticulata neurons, and suggests that
glutamatergic mechanisms play a role in delayed transneuronal degeneration.
PMID- 10188936
TI - The effects of temperature and scopolamine on N-methyl-D-aspartate antagonist
induced neuronal necrosis in the rat.
AB - The effects of temperature and scopolamine on dizocilpine maleate-induced
neuronal necrosis in the rat cingulate/retrosplenial cortex, entorhinal/olfactory
cortices and the dentate gyrus were studied. Mild, protracted hypothermia (48 h
at a brain temperature of 34 degrees C), induced by a servo-controlled "exposure
technique" in the awake female rat, significantly reduced dizocilpine maleate
(5.0 mg/kg, i.p.)-induced neuronal death in the cingulate/retrosplenial and
entorhinal/olfactory cortices seven days following drug administration.
Scopolamine (0.25 mg/kg, i.p.), putatively neuroprotective [Olney J. W. et al.
(1991) Science 254, 1515-1518], did not reduce injury in the
cingulate/retrosplenial cortex of female rats following one injection, but did
following two and three doses. Scopolamine had no significant effect in the other
brain regions. A temperature elevation of only 1 degree C above baseline for 48 h
in awake female rats increased dizocilpine maleate-induced damage. Finally, the
sex differences in N-methyl-D-aspartate antagonist toxicity were replicated and
extended to other structures, and found not to be due to temperature differences.
Our data show that dizocilpine maleate neurotoxicity is temperature sensitive.
Scopolamine treatment needed to be prolonged in order to reduce injury, and even
then was only efficacious in one of three brain regions. The results underscore
the importance of using neuronal necrosis in several brain regions as the
endpoint and for the use of prolonged therapeutic interventions. Furthermore,
given the potential hypothermic action of other putative neuroprotective drugs, a
mechanistic re-evaluation of N-methyl-D-aspartate antagonist-induced injury is
needed, with precise brain temperature measurement.
PMID- 10188937
TI - Activation of muscarinic M3-like receptors and beta-adrenoceptors, but not M2
like muscarinic receptors or alpha-adrenoceptors, directly modulates
corticostriatal neurotransmission in vitro.
AB - The aim of this study was to characterize the modulation of synaptic transmission
in the glutamatergic corticostriatal pathway by cholinergic and adrenergic
receptors. In coronal slices of mouse brain, negative-going field potentials were
recorded in the dorsal striatum in response to stimulation of the overlying white
matter, and their susceptibility to various pharmacological manipulations was
studied. The responses were mediated by alpha-amino-3-hydroxy-5-methyl-4
isoxazolepropionic acid (AMPA)-type glutamate receptors, since they were
augmented by aniracetam (0.5-1.5 mM), a positive modulator of AMPA-type glutamate
receptors, and blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (> or = 10
microM), a selective antagonist of AMPA receptors. Carbachol (10 microM), a
muscarinic agonist, reduced the size of responses and abolished paired-pulse
depression; these effects being consistent with previous studies indicating that
muscarinic activation inhibits release of glutamate in the corticostriatal
pathway. Muscarinic antagonists could block the effect of carbachol. Their rank
order was: 10 microM scopolamine (a non-selective muscarinic antagonist) > or = 1
microM 4-diphenylacetoxy-N-methyl-piperidine (M3/M1 antagonist)>1 microM
pirenzepine (M1 antagonist)>10 microM methoctramine (M2 antagonist). McN-A-343 (1
10 microM), an M1 muscarinic agonist, was ineffective in this preparation. In
contrast, isoproterenol (10-30 microM), a beta-adrenergic agonist, slightly
increased the synaptic responses, but it did not affect paired-pulse depression.
None of alpha-adrenergic agents (30 nM-1.0 microM dexmedetomidine, an alpha2
adrenergic agonist, 0.3 microM atipamezole, an alpha2-adrenergic antagonist or 30
microM phenylephrine, an alpha1-adrenergic agonist) influenced the size of the
responses; neither did these drugs alter paired-pulse depression. These results
indicate that the activation of striatal M3-like muscarinic receptors and beta
adrenoceptors, but not M2-like muscarinic receptors and alpha-adrenoceptors,
modulates directly corticostriatal glutamatergic neurotransmission.
PMID- 10188938
TI - N-methyl-D-aspartate receptor 1 in the caudate-putamen nucleus: ultrastructural
localization and co-expression with sorcin, a 22,000 mol. wt calcium binding
protein.
AB - Entry of calcium through N-methyl-D-aspartate-type glutamate receptors in the
caudate-putamen nucleus is essential for normal motor activity, but can produce
cytotoxicity with continued stimulation and subsequent release of intracellular
calcium. To determine potential functional sites for N-methyl-D-aspartate
receptor activation in this region, we examined the ultrastructural localization
of the R1 subunit of the N-methyl-D-aspartate receptor (NMDAR1) in rat brain. In
addition, we comparatively examined the localization of NMDAR1 and sorcin, a
22,000 mol. wt calcium binding protein present in certain striatal neurons and
involved in calcium-induced calcium release. NMDAR1-like immunoreactivity was
seen at synaptic and non-synaptic sites on neuronal plasma membranes. Of 1514
NMDAR1-labeled profiles, 62% were dendrites and dendritic spines and the
remainder were mainly unmyelinated axons and axon terminals. Sorcin-like
immunoreactivity was present in 39% of the profiles that contained NMDAR1
labeling, most (533/595) of which were dendrites and dendritic spines. Of 1807
sorcin-labeled profiles, 42% were identified, however, as small processes
including spine necks and unmyelinated axons or axon terminals. These profiles
also occasionally contained NMDAR1 or showed synaptic or appositional contacts
with other NMDAR1-immunoreactive neurons. The results of this study suggest that
in the caudate-putamen nucleus, activation of NMDA receptors permits calcium
influx at plasmalemmal sites mainly on dendrites where sorcin may play a role in
calcium-induced calcium release. The presence of sorcin in some, but not all NMDA
containing neurons in the caudate-putamen nucleus has potential implications for
the known differential vulnerability of certain striatal neurons to excitotoxins.
PMID- 10188939
TI - Enhanced dopamine efflux in the amygdala by a predictive, but not a non
predictive, stimulus: facilitation by prior repeated D-amphetamine.
AB - Extracellular levels of dopamine within the amygdala were monitored using in vivo
microdialysis during performance of an appetitive Pavlovian conditioning task in
sensitized rats and unsensitized controls. Animals received exposure either to D
amphetamine or to vehicle for seven consecutive days (2 mg/kg/day, i.p.) in the
home cage. Training began following a further seven injection-free days. Animals
were exposed to two session types: during conditioning sessions, a stimulus (tone
or light) immediately preceded sucrose pellet delivery. During control sessions,
the alternative stimulus was also presented, but not in temporal proximity to an
otherwise identical schedule of pellet delivery. There was a total of three
alternating presentations of each session type during training. Sensitization
enhanced Pavlovian conditioned approach behaviour to the stimulus predictive of
imminent pellet delivery, and was without effect upon approach behaviours either
to the food pellets themselves or to the control stimulus. Extracellular levels
of dopamine within the amygdala were assessed during the fourth conditioning and
control sessions. Mesoamygdaloid dopamine efflux increased significantly during
the conditioning test session, but not during the control session, and this
dopaminergic response was more marked in rats with prior repeated D-amphetamine
experience. Hence, these results add to evidence suggesting a role for amygdaloid
dopamine in appetitive Pavlovian conditioning, and in the facilitation of
associative learning following prior experience of D-amphetamine.
PMID- 10188940
TI - Neurochemical evidence of dopamine release by lateral olivocochlear efferents and
its presynaptic modulation in guinea-pig cochlea.
AB - In this study, using an in vitro superfusion technique for the first time, we
provide direct neurochemical evidence of the transmitter role of dopamine at the
level of lateral olivocochlear efferent fibres of the guinea-pig cochlea. Our
results revealed that nerve terminals are able to take up and release dopamine
upon axonal stimulation. Since dopamine is thought to protect the afferent nerve
fibres from damage due to acoustic trauma or ischaemia, enhancement of the
release of dopamine, a potential therapeutic site of these injuries, was
investigated. Positive modulation of dopamine release has been shown by a D1
dopamine receptor agonist, an antagonist and piribedil. Furthermore, negative
feedback on the stimulation-evoked release of dopamine via D2 dopamine receptors
has been excluded. Electrical stimulation of the cochlear tissue produced a
significant and reproducible release of [3H]dopamine, which could be blocked by
tetrodotoxin (1 microM) and cadmium (100 microM), proving that axonal activity
releases dopamine and its dependence on Ca2+ influx verifies its neuronal origin.
Nomifensine, a high-affinity dopamine uptake blocker, prevented the tissue from
taking up [3H]dopamine from the bathing solution, also indicating the neural
origin of dopamine released in response to stimulation. SKF-38393 (a selective D1
agonist) increased both the resting and electrically evoked release of dopamine.
Piribedil (a D3/D2/D1 agonist), a drug under investigation, known to prevent
acoustic trauma or ischaemia-induced hearing loss, had a similar and
concentration-dependent increasing effect on both resting and evoked release of
dopamine. The effect of both drugs on stimulation-evoked release could be
prevented by SKF-83566 (a selective D1 antagonist). However, SKF-83566 alone
enhanced the resting and axonal conduction-associated release of dopamine. D2
agonists and antagonists failed to modulate the release of dopamine, indicating
the lack of negative feedback modulation of dopamine release. Our results suggest
that the release of dopamine was subjected to modulation by a D1 receptor agonist
and an antagonist. In addition, it is concluded that D2 receptors are not
involved in the modulation of dopamine release. This observation may have
clinical relevance in the prevention or therapy of particular types of hearing
loss, because enhanced dopaminergic input into the primary auditory neuron may
inhibit the (over)excitation of this neuron by glutamatergic input from inner
hair cells.
PMID- 10188941
TI - Summation between acoustic and trigeminal stimuli evoking startle.
AB - Electrical stimulation of the spinal trigeminal pathway evokes a short-latency
startle-like response in rats. To explore the relationship between acoustic and
tactile systems mediating startle, we studied temporal summation between pairs of
startle-evoking stimuli in awake rats by varying the interstimulus interval. The
stimuli were: (i) two noise bursts; (ii) two unilateral electrical stimuli near
the principal nucleus of the trigeminal nerve; (iii) electrical stimulation of
the left and right trigeminal nucleus; or (iv) a noise burst and unilateral
stimulation of the trigeminal nucleus. Following two noise bursts, the amplitude
of startle increased as the interval increased from 0 to 4 ms, then declined
smoothly as the interval increased to 15 ms. Unilateral stimulation of the
trigeminal nucleus resulted in a sharper summation effect, with maximal summation
at 2 ms, and refractory periods estimated at 0.4-0.8 ms. Bilateral stimulation of
the trigeminal nucleus resulted in broader summation without a refractory period,
and maximal summation when the stimuli on both sides of the trigeminal nucleus
were presented simultaneously. The combination of acoustic and trigeminal
stimulation was most effective in enhancing startle amplitudes, and summation
peaked when the noise burst preceded the trigeminal stimulation by 5 ms.
Similarly, electromyogram latencies measured in the hindlimb were 3-4 ms shorter
for trigeminal stimulation than for the noise burst. Startle appears to be
optimally activated by simultaneous acoustic and tactile stimuli, as occurs
during head blows.
PMID- 10188942
TI - The sodium channel auxiliary subunits beta1 and beta2 are differentially
expressed in the spinal cord of neuropathic rats.
AB - Neuropathic pain is thought to arise from ectopic discharges at the site of
injury within the peripheral nervous system, and is manifest as a general
increase in the level of neuronal excitability within primary afferent fibres and
their synaptic contacts within the spinal cord. Voltage-activated Na+ channel
blockers such as lamotrigine have been shown to be clinically effective in the
treatment of neuropathic pain. Na+ channels are structurally diverse comprising a
principal a subunit (of which there are variable isoforms) and two auxiliary
subunits termed beta1 and beta2. Both beta subunits affect the rates of channel
activation and inactivation, and can modify alpha subunit density within the
plasma membrane. In addition, these subunits may interact with extracellular
matrix molecules to affect growth and myelination of axons. Using in situ
hybridization histochemistry we have shown that the expression of the beta1 and
beta2 subunits within the dorsal horn of the spinal cord of neuropathic rats is
differentially regulated by a chronic constrictive injury to the sciatic nerve.
At days 12-15 post-neuropathy, beta1 messenger RNA levels had increased, whereas
beta2 messenger RNA levels had decreased significantly within laminae I, II on
the ipsilateral side of the cord relative to the contralateral side. Within
laminae III-IV beta2 messenger RNA levels showed a small but significant decrease
on the ipsilateral side relative to the contralateral side, whilst expression of
beta1 messenger RNA remained unchanged. Thus, differential regulation of the
individual beta subunit types may (through their distinct influences on Na+
channel function) contribute to altered excitability of central neurons after
neuropathic injury.
PMID- 10188943
TI - Antidromic discharges of dorsal root afferents and inhibition of the lumbar
monosynaptic reflex in the neonatal rat.
AB - The in vitro brain stem-spinal cord preparation of neonatal (0- to five-day-old)
rats was used to establish whether pathways descending from the brain stem are
capable of modulating synaptic transmission from primary afferents to lumbar
motoneurons within the first few days after birth. We stimulated the ventral
funiculus of the spinal cord at the cervical (C1-C2) level. Single-pulse
stimulations evoked both excitatory and inhibitory postsynaptic potentials in
ipsilateral lumbar (L2-L5) motoneurons which were recorded intracellularly. Twin
pulse stimulations evoked bursts of action potentials in ventral roots. The
amplitude of the monosynaptic dorsal root-evoked excitatory postsynaptic
potential decreased when a conditioning stimulation was applied to the ventral
funiculus 50-300 ms prior to the stimulation of the ipsilateral dorsal root. A
decreased input resistance of the motoneurons during the early part (25-100 ms
after the artifact) of the ventral funiculus-evoked postsynaptic potentials could
account, at least partly, for the decreased amplitude of the dorsal root-evoked
response. However, the duration of the inhibition of the dorsal root-evoked
excitatory postsynaptic potential was longer than that of the decrease in input
resistance. Ventral funiculus stimulation evoked antidromic discharges in dorsal
roots. Recordings of dorsal root potentials showed that these discharges were
generated by the underlying afferent terminal depolarizations reaching firing
threshold. The dorsal root discharge overlapped with most of the time-course of
the ventral funiculus-evoked inhibition of the response to dorsal root
stimulation, suggesting that part of this inhibition may be exerted at a
presynaptic level. The number of antidromic action potentials evoked in dorsal
roots by ventral funiculus stimulation increased significantly in saline solution
with chloride concentration reduced to 50% of control. Bursts of action
potentials disappeared when chloride was removed completely. Antidromic
discharges were therefore due to chloride conductance. The number of action
potentials evoked in ventral roots was increased in low-chloride saline
solutions. Removing chloride from the bathing solution resulted in an unstable
ventral root activity. Bath application of the GABA(A) receptor antagonist,
bicuculline (5-10 microM), blocked the ventral funiculus-evoked antidromic
discharges in the dorsal roots. The increase in chloride conductance which
generated the depolarizations underlying the dorsal root discharges was therefore
mediated by an activation of GABA(A) receptors. In contrast, bursts of action
potentials in the ventral roots were increased in both amplitude and duration
under bicuculline. Our data demonstrate that pathways running in the ventral
funiculus of the spinal cord exert a control on interneurons mediating
presynaptic inhibition at birth.
PMID- 10188944
TI - Differences in opioidergic inhibition of spinal reflexes and Fos expression
evoked by mechanical and chemical noxious stimuli in the decerebrated rabbit.
AB - Noxious mechanical and chemical stimuli were applied to the toes of the left hind
limb of decerebrated, spinalized rabbits and their effects on a hind limb spinal
withdrawal reflex and expression of Fos-like immunoreactivity in the spinal cord
were measured. The animals were prepared so as to minimize nociceptive inputs
arising from surgery. A single crush stimulus applied with a pair of haemostatic
forceps caused long-lasting (c. 20 min) inhibition of reflexes evoked in medial
gastrocnemius motoneurons by electrical stimulation of the skin at the heel.
Naloxone (0.25 mg/kg i.v.) increased reflexes to more than 1000% of pre-drug
controls and reversed crush-evoked inhibition. Mustard oil applied to the toes
had no consistent effects on the heel-gastrocnemius reflex before or after
naloxone. Both crush and mustard oil stimuli gave rise to unilateral increases in
the number of Fos-immunopositive profiles in the superficial dorsal horn of
spinal segments L7 and S1. There were significantly more Fos-immunoreactive
elements in the central and lateral parts of lamina I of both segments in animals
receiving the crush stimulus than there were in animals receiving the mustard oil
stimulus. Immunochemical localization of enkephalins in rabbit spinal cord showed
a dense network of fibres and terminals in laminae I and II, accompanied by
infrequent but distinctly stained neuronal cell bodies. The same pattern, with
increased numbers of visible cell bodies, was seen after treatment with
colchicine. The present data show that tonic and stimulus-evoked opioidergic
inhibition of the heel-gastrocnemius reflex of the rabbit are not epiphenomena of
surgical preparation of the hindlimb. Opioid-mediated inhibition of the heel
gastrocnemius withdrawal reflex of the rabbit was evoked by noxious mechanical
but not by chemical stimulation of the toes. Of these stimuli, the former gave
rise to greater activation of neurons in central and lateral lamina I of segments
L7 and S1, the region of termination of afferent fibres from the heel and the
location of some enkephalin-positive neuronal cell bodies. Thus, noxious
mechanical stimulation of the toes elicits inhibition of the heel-gastrocnemius
withdrawal reflex, probably via activation of enkephalinergic neurons in the
lateral half of lamina I in the L7 and S1 segments.
PMID- 10188945
TI - Spinal section and opioid receptor blockade induce the appearance of Fos-like
immunoreactivity in the spinal cord of the decerebrated rabbit.
AB - The expression of Fos-like immunoreactivity has been studied in spinal segments
L5-S1 of decerebrated, unanaesthetized, but otherwise unstimulated rabbits. The
aim of the study was to establish baseline levels of Fos in such preparations,
and to examine how these might change after spinalization and opioid receptor
blockade. In animals with an intact spinal cord, approximately 30 Fos-positive
profiles per section were found in the superficial dorsal horns (i.e. laminae I
and II) of each 40-microm section, while about 20 profiles per section were found
immediately adjacent to the central canal (lamina X). Fos-like immunoreactive
profiles were rare elsewhere in the gray matter. When the spinal cord was
sectioned at L1 (after blockade with local anaesthetic), significantly more Fos
like immunoreactivity was found in superficial and central regions of the gray
matter (approximately 90 profiles per section) in animals perfused 4 h after
decerebration, but not when perfusion was performed 2 or 8 h after decerebration.
The opioid antagonist naloxone (0.25 mg/kg/h) had little effect on expression of
Fos-like immunoreactivity in spinalized preparations, but significantly increased
the numbers of Fos-positive profiles in all but the ventral areas of the spinal
gray matter in non-spinalized preparations. The present data show that spinal
section induces a transient increase in expression of Fos in the superficial and
central parts of the spinal gray matter. It appears that spinalization induces
spontaneous activity in some neurons in these regions of the cord, presumably as
a result of relief of descending inhibition. The effects of naloxone indicate
that endogenous opioids exert tonic inhibition over Fos-expressing spinal neurons
in non-spinalized rabbits.
PMID- 10188946
TI - Nociceptive stimulation induces glutamate receptor down-regulation in the
trigeminal nucleus.
AB - The dorsal horn of the subnucleus caudalis of the spinal trigeminal nucleus is a
relay of oro-facial pain transmission; increase in subnucleus caudalis neuronal
activity in response to tissue injury affects the level of chemical mediators
participating in nociceptive processing. We investigated, by means of
immunocytochemistry, the expression of N-methyl-D-aspartate and alpha-amino-3
hydroxy-5-methyl-4-isoxazolepropionate (AMPA) glutamate receptor subunits in this
nucleus in a model of inflammation. Rats injected with formalin in the whisker
pad were compared with saline-injected control rats. One and two days after
formalin injection, the immunostaining of cell bodies and neuropil of the AMPA
receptor subunits GluR1 and GluR2/3 was markedly decreased in the ipsilateral
superficial laminae of the subnucleus caudalis compared to the contralateral
side. Side differences were not evident in the saline-treated animals. The down
regulation of AMPA GluR1 and GluR2/3 was no longer detectable in the subnucleus
caudalis three days after formalin injection. No side difference was detected in
the N-methyl-D-aspartate receptor subunit NR2A/B immunoreactivity of the
subnucleus caudalis at any time-point in the formalin-injected animals. The
modulation of AMPA receptor may be related to the decrease of hyperalgesia
evident 1 h after formalin injection, in spite of the increasing perioral
inflammation evident later on and characteristic of the formalin model. The
present findings point out a selective down-regulation of AMPA receptor subunits
in the transduction of trigeminal pain. These data also support the involvement
of glutamate receptor subunits in the processing of trigeminal inflammation
induced by noxious chemical stimulation.
PMID- 10188947
TI - Mu-opioid agonist-induced activation of G-protein-coupled inwardly rectifying
potassium current in rat periaqueductal gray neurons.
AB - The characteristics of the inwardly rectifying K+ current activated by a mu-type
opioid agonist, D-Ala2,N-MePhe4,Gly5-ol-enkephalin (DAMGO), were examined in the
acutely dissociated rat periaqueductal gray neurons using the nystatin-perforated
and the conventional whole-cell recording modes under voltage-clamp conditions.
DAMGO activated inward currents in a concentration- and voltage-dependent manner.
The DAMGO-induced current was an inwardly rectifying K+ current (I(DAMGO)) which
was sensitive to K+ channel blockers, quinine and Ba2+ but insensitive to Cs+ and
tetraethylammonium. In the conventional whole-cell clamp mode, guanosine 5'-O-(2
thiodiphosphate) trilithium salt (GDPbetas, 0.4 mM) inhibited the amplitude of
I(DAMGO) to 28% of that of the initial current. After the intracellular perfusion
with guanosine 5'-O-(3-thiotriphosphate) tetralithium salt (GTPgammas, 0.4 mM)
for 1 min, the first application of DAMGO irreversibly activated I(DAMGO). By the
extracellular application of N-ethylmaleimide at a concentration of 50 microM for
2 min, I(DAMGO) was completely abolished. When a conventional whole-cell patch
was made with a patch-pipette containing 1 microg/ml of pertussis toxin together
with 1 mM of beta-nicotinamide adenine dinucleotide, I(DAMGO) gradually declined
to about 41% of its initial amplitude. The extracellular application of second
messenger modulators including protein kinase inhibitor (staurosporin), protein
kinase A activators (forskolin, 3-isobutyl-l-methyl-xanthine and
dibutyryladenosine 3'5'-cyclic monophosphate) and protein kinase C activators
(phorbol-12-myristate-13-acetate and 1-oleoyl-2-acetyl-sn-glycerol) had no effect
on I(DAMGO). These results suggest that (i) DAMGO-activated inwardly rectifying
K+ current is mediated by pertussis toxin-sensitive guanine nucleotide binding
proteins (G-proteins); (ii) the types of G protein involved in I(DAMGO) are Gi
and/or Go; and (iii) the G-proteins exert their roles in I(DAMGO) without any
mediation of the second messenger systems.
PMID- 10188948
TI - Tachykinin receptors are involved in the "local efferent" motor response to
capsaicin in the guinea-pig small intestine and oesophagus.
AB - The sensory neuron stimulant drug capsaicin stimulates primary afferent nerve
endings in the guinea-pig small intestine, which in turn activate myenteric
cholinergic neurons by an unknown mechanism. The tachykinins substance P and
neurokinin A are present in primary afferent neurons. This study was performed to
assess the possible involvement of endogenous tachykinins acting via neurokinin
1, neurokinin-2 and neurokinin-3 receptors in the contractile effect of capsaicin
in the isolated guinea-pig ileum and oesophagus by using the receptor-specific
antagonists GR 82334 (3 microM) for neurokinin-1 receptors, MEN 10627 (3 microM;
ileum) or MEN 11420 (1 microM; oesophagus) for neurokinin-2 receptors and SR
142801 (0.1 microM) for neurokinin-3 receptors. In the ileum, the peak
contraction evoked by capsaicin (2 microM) was not reduced when tachykinin
neurokinin-1, neurokinin-2 or neurokinin-3 receptors were blocked separately,
whereas an inhibition of neurokinin-3 receptors diminished the area under the
curve of the capsaicin response. A combined blockade of neurokinin-1 and
neurokinin-3 receptors significantly depressed the effect of capsaicin; the
amplitude of the contractile response was 53.3+/-3.7% of the maximal longitudinal
spasm in control preparations, whereas in the presence of GR 82334 plus SR 142801
it reached only 27.6+/-5% (P<0.001, Kruskal-Wallis test; n=9 and 10,
respectively). Also, the area under the curve of the contractile response to
capsaicin was more than 85% lower in the group of preparations treated with GR
82334 plus SR 142801 than in the control group (P<0.001). Including a neurokinin
2 blocker in the combination did not produce any further inhibition. A
concomitant tachyphylaxis to substance P (natural neurokinin-1 receptor
stimulant) and the neurokinin-3 receptor agonist senktide (5 and 1 microM,
respectively) also reduced the contractile effect of capsaicin. In the
oesophagus, capsaicin (1 microM) induced biphasic contractions which were
strongly inhibited by atropine (1 microM) or capsaicin pretreatment (1 microM for
10 min). Here again, a blockade of tachykinin neurokinin-1, neurokinin-2 or
neurokinin-3 receptors separately failed to inhibit the response to capsaicin,
whereas a combined blockade of any two tachykinin receptors caused a partial
inhibition. The reduction of the contractile effect of capsaicin was strongest
when all three tachykinin receptors were blocked. In seven control preparations,
peaks for the first and second phases of contraction reached 35.3+/-3.7% and 20+/
3.2% of maximal longitudinal spasm; the corresponding values in the presence of a
combination of GR 82334, MEN 11420 and SR 142801 were 7.5+/-0.8% and 9.1+/-2.2%,
respectively (n=6, P<0.001 and 0.05, respectively). Tetrodotoxin (0.5 microM)
practically abolished the contractile effect of capsaicin in both tissues
studied. It is concluded that an interplay of neuronal tachykinin neurokinin-1
and neurokinin-3 receptors (ileum) and neurokinin-1, neurokinin-2 and neurokinin
3 receptors (oesophagus) is involved in the contractile action of capsaicin,
probably in mediating excitation of myenteric neurons by tachykinins released
from primary afferents. In both tissues, there also seems to be a non
tachykininergic component of the capsaicin-induced contraction.
PMID- 10188949
TI - Serotonergic and GABAergic neurons in the medial rostral ventral medulla express
kappa-opioid receptor immunoreactivity.
AB - Activation of kappa-opioid receptors in the rostral ventral medulla has been
reported to attenuate analgesia induced by activation of mu-opioid receptors in
the periaqueductal gray matter. Previous studies have suggested that the cells
associated with this effect might contain serotonin. In the present study, we
investigated the relationship of the cloned kappa-opioid receptor to spinally
projecting neurons immunoreactive for serotonin or GABA. This was done by
employing two-color immunofluorescence in combination with retrograde tract
tracing using Fluoro-Gold. In the rostral ventral medulla, neurons triple-labeled
for the cloned kappa-opioid receptor, serotonin and Fluoro-Gold were observed;
neurons double-labeled for the cloned kappa-opioid receptor and serotonin, or
single-labeled for the cloned kappa-opioid receptor or for serotonin were also
observed. In addition, cloned kappa-opioid receptor immunoreactivity was
expressed in some cell profiles immunoreactive for GABA. The expression of the
cloned kappa-opioid receptor in the spinal cord dorsal horn was not associated
with processes immunoreactive for serotonin. Our findings suggest that kappa
opioid receptors in the rostral ventral medulla are positioned to directly
control the activity of at least some serotonergic neurons projecting to the
dorsal spinal cord. Thus, it appears possible that the anti-analgesic action
resulting from microinjection of kappa-opioid agonists into the rostral ventral
medulla is mediated, at least in part, by these neurons.
PMID- 10188950
TI - Regulation of pituitary adenylate cyclase activating polypeptide and its receptor
type 1 after traumatic brain injury: comparison with brain-derived neurotrophic
factor and the induction of neuronal cell death.
AB - Neurotrophic factors are known to promote neuronal survival during development
and after acute brain injury. Recent data suggest that some neuropeptides also
exhibit neurotrophic activities, as shown for the pituitary adenylate cyclase
activating polypeptide, which increases the survival of various neuronal
populations in culture. Employing in situ hybridization techniques, we have
studied the regulation of messenger RNA for pituitary adenylate cyclase
activating polypeptide and its receptor type 1 after a moderate traumatic brain
injury to rat brain cortex. We have further compared their messenger RNA
expression to that of brain-derived neurotrophic factor and to the amount of cell
death occurring in the brain at various times after the brain injury. Levels of
brain-derived neurotrophic factor messenger RNA increased rapidly within 2 h
after trauma in cortex and hippocampus, and returned to control levels
thereafter. The levels of messenger RNA for pituitary adenylate cyclase
activating polypeptide also increased with time in the injured brains and reached
maximal expression at 72 h, i.e. the end of the observation period. The
alterations in pituitary adenylate cyclase activating polypeptide messenger RNA
levels were particularly pronounced in the perifocal region and in the
ipsilateral dentate gyrus of the brain injury. In contrast, the messenger RNA
levels encoding pituitary adenylate cyclase activating polypeptide receptor type
1 first decreased after trauma and were then normalized in the dentate gyrus.
There was a large increase in the number of cells labelled for DNA breaks at 12 h
post-trauma, indicative of enhanced cell death. The number of labelled cells,
however, decreased at later stages concomitant with an increase in the expression
of pituitary adenylate cyclase activating polypeptide messenger RNA. Pituitary
adenylate cyclase activating polypeptide rescued cortical neurons in cultures
against ionomycin-induced cell death, supporting the concept of a neuroprotective
effect for the peptide. These results demonstrate a differential regulation of
messenger RNA for brain-derived neurotrophic factor and the pituitary adenylate
cyclase activating polypeptide and its receptor after brain trauma. The data also
suggest that pituitary adenylate cyclase activating polypeptide might have a
beneficial effect in brain injury by counteracting neuronal cell death.
PMID- 10188951
TI - Ambiguous respiratory neurons are modulated by GABA(A) receptor-mediated
inhibition.
AB - A group of respiratory neurons in the rostral nucleus ambiguus complex is known
to generate the inspiratory and expiratory drives which enable spontaneous
respiration to be sustained. Since previous studies indicated that mutual
synaptic inhibition is required to produce oscillations between inspiratory and
expiratory neurons, it may implicate GABAergic synaptic transmission between each
group of neurons. In this study we tried to determine whether most ambiguous
respiratory neurons are influenced by GABA(A) receptor-mediated inhibition.
Eighty-eight respiratory interneurons showing rhythmic activity in synchrony with
the spontaneous respiration were recorded in urethane-chloralose anesthetized
Wistar rats. Multibarrel iontophoretic application of GABA(A) antagonist
bicuculline produced a remarkable facilitation in maximum burst discharge rate,
whereas the agonist muscimol reversed this effect completely. Simultaneous
application of GABA and bicuculline increased the discharge rate more than in any
single application or in the simultaneous application of GABA and muscimol. These
results were statistically significant. These findings suggest strongly that
GABA(A) receptors in the ambiguous respiratory neurons may have an inhibitory
role in the synaptic transmission for maintaining the respiratory oscillation in
the nucleus ambiguus.
PMID- 10188953
TI - Antibodies against the beta subunit of voltage-dependent calcium channels in
Lambert-Eaton myasthenic syndrome.
AB - Lambert-Eaton myasthenic syndrome is an autoimmune disease that impairs
neuromuscular transmission. Several studies suggest that neurotransmitter release
is reduced by an immune response directed against the calcium channel complex of
nerve terminals. The immunoglobulin G fractions from Lambert-Eaton myasthenic
syndrome patients immunoprecipitate solubilized neuronal N- and P/Q-type channels
and in certain cases brain, skeletal and cardiac muscle L-type channels [El Far
O. et al. (1995) J. Neurochem. 64, 1696-1702; Lennon V. A. and Lambert E. H.
(1989) Mayo Clin. Proc. 64, 1498-1504; Sher E. et al. (1989) Lancet ii, 640-643;
Suenaga A. et al. (1996) Muscle Nerve 19, 1166-1168]. These channel
immunoprecipitation assays are considered as useful for the diagnosis of this
syndrome. In this study, we demonstrate that two predominant neuronal voltage
dependent calcium channel beta subunits (beta3 and beta4, of mol. wt 58,000) are
general targets of Lambert-Eaton myasthenic syndrome autoantibodies. Of 20
disease sera tested, 55% were able to immunoprecipitate 35S-labeled beta
subunits. All five patients affected with small-cell lung carcinoma were positive
for the beta-subunit immunoprecipitation assay. Interestingly, only a fraction of
the beta-subunit-positive sera was also able to immunoprecipitate N- and P/Q-type
channels, suggesting that several of the beta-subunit epitopes are masked in
native channels. In accordance with this observation, we found that several beta
positive sera were able to prevent the interaction between calcium channel alpha1
and beta subunits in vitro. In cases where sera were able to immunoprecipitate
beta subunits, N- and P/Q-type channels, the immunoprecipitation of both channel
types was either partially or entirely mediated by beta-subunit antibodies. Our
results suggest that assays based on the immunoprecipitation of beta subunits can
be used as an additional test to assist in the diagnosis of Lambert-Eaton
myasthenic syndrome.
PMID- 10188952
TI - A role for p75 receptor in neurotrophin-3 functioning during the development of
limb proprioception.
AB - Neurotrophin-3 is indispensable for the development of limb proprioceptive
neurons and their end organs, muscle spindles. To determine whether the low
affinity p75 receptor potentiates the actions of neurotrophin-3, we examined the
development of the proprioceptive system in p75 null mutant mice that had either
normal or decreased tissue levels of neurotrophin-3. Postnatal mice lacking both
copies of the p75 gene had fewer sensory neurons in dorsal root ganglia, but
normal complements of muscle spindles in fast hindlimb muscles, although the slow
soleus muscle showed a 50% loss of spindles. However, compound mutants lacking
both copies of the p75 gene as well as one copy of the neurotrophin-3 gene
displayed a dystonic/ataxic phenotype similar to that observed previously in
neurotrophin-3 null mutants devoid of proprioception. The compound mutants also
exhibited a commensurate loss of parvalbumin-expressing (proprioceptive) neurons
in dorsal root ganglia. The degree of deficiency of spindles (and presumably
proprioceptive neurons) in the compound mutants exceeded the sum of deficits in
single mutants lacking either both copies of p75 genes or one copy of
neurotrophin-3 gene, suggesting a synergistic interaction between the p75
receptor and neurotrophin-3. Neuronal deficits in the compound mutants were
present prior to embryonic day 14, indicating an early role for the p75 receptor
in sensory neuronogenesis. Collectively, these data indicate that the p75
receptor is not essential for the survival and differentiation of most limb
proprioceptive neurons when neurotrophin-3 is expressed at normal levels.
However, the p75 receptor may act in synergy with neurotrophin-3 to enhance the
survival of proprioceptive neurons when tissue levels of neurotrophin-3 are a
limiting factor.
PMID- 10188954
TI - Long-term effects of synaptic activation at low frequency on excitability of
myenteric AH neurons.
AB - Intracellular microelectrodes were used to record the effects of extended periods
(1-30 min) of synaptic activation on AH neurons in the myenteric ganglia of the
guinea-pig ileum. Low-frequency (1 Hz) stimulation gave rise to a slowly
developing, sustained increase in excitability of the neurons associated with
depolarization and increased input resistance. The increased excitability lasted
for up to 3.5 h following the stimulus period. Successive stimulus trains (1-4
min) elicited successively greater increases in excitability. The neurons went
through stages of excitation. Before stimulation, 500-ms depolarizing pulses
evoked up to three action potentials (phasic response) and anode break action
potentials were not observed. As excitability increased, more action potentials
were evoked by depolarization (the responses became tonic), anode break action
potentials were observed, prolonged after hyperpolarizing potentials that follow
multiple action potentials were diminished and, with substantial depolarization
of the neurons, invasion by antidromic action potentials was suppressed. It is
concluded that a state of elevated excitability is induced in myenteric AH
neurons by synaptic activation at low frequency and that changes in excitability
can outlast stimulation by several hours.
PMID- 10188955
TI - Modulation of cholinergic transmission in the neuronal network of the gill and
siphon withdrawal reflex in Aplysia.
AB - Inhibitory interneurons are important elements of the network underlying the gill
and siphon withdrawal reflex in Aplysia, and a large component of this inhibition
is cholinergic. In this study, we investigated one key identified cholinergic
inhibitory interneuron of the network, neuron L16, and studied some properties of
its synaptic transmission and its modulation. We found that a slow inhibitory
postsynaptic potential evoked in sensory neurons by L16 has two components. An
earlier inhibitory postsynaptic potential component is sensitive to curare (100
microM) and has a reversal potential near the Cl- equilibrium potential (-54.5
mV). A later inhibitory postsynaptic potential component is sensitive to
tetraethylammonium (0.5-1 mM); it is decreased by membrane hyperpolarization and
becomes undetectable near the K+ equilibrium potential (between -80 and -90 mV).
Input to sensory neurons from L16 can be altered by two neuromodulators of the
reflex, the small cardioactive peptide and serotonin. Small cardioactive peptide
(10 microM) facilitates the connections between L16 and the sensory neurons,
while serotonin (5-10 microM) inhibits them. Part of the effect of serotonin on
the transmission between L16 and the sensory neurons is due to a postsynaptic
mechanism, since responses to acetylcholine application in these cells are
decreased by serotonin. These results indicate an additional site of synaptic
plasticity in the withdrawal reflex network, the inhibitory cholinergic
transmission, by two major neuromodulatory transmitters, small cardioactive
peptide and serotonin.
PMID- 10188956
TI - Cloning, expression and electrophysiological characterization of glycine receptor
alpha subunit from zebrafish.
AB - The glycine receptor is a ligand-gated anion channel protein, providing
inhibitory drive within the nervous system. We report here the isolation and
functional characterization of a novel alpha subunit (alphaZ1) of the glycine
receptor from adult zebrafish (Danio rerio) brain. The predicted amino acid
sequence is 86%, 81% and 77% identical to mammalian isoforms alpha1, alpha3 and
alpha2, respectively. AlphaZ1 exhibits many of the molecular features of
mammalian alpha1, but the sequence patterns in the M4 and C-terminal domains are
more similar to alpha2/alpha3. Phylogenetic analysis indicates that alphaZ1 is
more closely related to the mammalian alpha1 subunits, being positioned, however,
on a distinct branch. The alphaZ1 messenger RNA is 9.5 kb, similar to that
described previously for alpha1 messenger RNAs. When expressed in Xenopus oocytes
or a human cell line (BOSC 23), alphaZ1 forms a homomeric receptor which is
activated by glycine and antagonized by strychnine. This receptor demonstrates
unexpectedly high sensitivity to taurine and can also be activated by GABA. These
results are consistent with physiological findings in lamprey and goldfish, and
they suggest that this teleost fish glycine receptor displays a lower selectivity
to neurotransmitters than that reported for glycine mammalian receptors.
PMID- 10188957
TI - Cellular and subcellular expression of monocarboxylate transporters in the
pigment epithelium and retina of the rat.
AB - The cellular and subcellular expression of the monocarboxylate transporters MCT1,
MCT2 and MCT4 [corresponding to MCT3 of Price N. T. et al. (1998) Biochem. J.
329, 321-328] were investigated in the pigment epithelium and outer retina of
rats. Immunofluorescence and postembedding immunogold analyses revealed strong
MCT1 labelling in the apical membrane of the pigment epithelial and no detectable
signal in the basolateral membrane. In contrast, antibodies to the glucose
transporter GLUT1 produced intense labelling in both membranes. Neither MCT1 nor
GLUT1 was enriched in intracellular compartments. The monocarboxylate transporter
MCT4 was very weakly expressed in the retinal pigment epithelium of adult
animals, but occurred at higher concentrations at this site in 14-day-old rats.
However, even at the latter stage, the immunolabelling of MCT4 was weak compared
to that of MCT1. In the neural retina, the data were consistent with a
predominant glial localization of MCT1. Specifically, immunogold particles
signalling MCT1 occurred in Muller cell microvilli and in the velate processes
between the photoreceptors. No labelling was obtained with antibodies to MCT2.
Taken together with previous biochemical analyses, the present findings indicate
that MCT1 is involved in the outward transport of lactate through the retinal
pigment epithelial cells, and in the transfer of lactate between Muller cells and
photoreceptors.
PMID- 10188958
TI - Alterations in expression of the neurotrophic factors glial cell line-derived
neurotrophic factor, ciliary neurotrophic factor and brain-derived neurotrophic
factor, in the target-deprived olfactory neuroepithelium.
AB - Neuronal growth factors play an important role in the development and maintenance
of the nervous system. In the olfactory system, neurogenesis and synapse
formation occur not only during development but throughout life and it would be
expected that growth factors play a significant role in these ongoing processes.
We have examined the expression of three neurotrophic factors, glial cell line
derived neurotrophic factor, ciliary neurotrophic factor and brain-derived
neurotrophic factor in the normal rat olfactory system and following synaptic
target ablation (olfactory bulbectomy). We found that brain-derived neurotrophic
factor immunoreactivity was confined to the horizontal basal cells of the
olfactory neuroepithelium and was unaltered by bulbectomy. Glial cell line
derived neurotrophic factor immunoreactivity was present in the mature olfactory
neurons and also their synaptic target cells in the olfactory bulb. Following
bulbectomy, glial cell line-derived neurotrophic factor immunoreactivity was
abolished from the neuroepithelium. Ciliary neurotrophic factor was present
throughout the olfactory neuronal lineage with strongest immunoreactivity in the
horizontal basal cells and mature olfactory neurons as well as several cell types
in the olfactory bulb. Postbulbectomy, there was loss of strong ciliary
neurotrophic factor immunoreactivity in olfactory neurons, however, low levels
persisted in the remaining neuronal population. Horizontal basal cell
immunoreactivity persisted over three months. Our results would be consistent
with glial cell line-derived neurotrophic factor expression in mature olfactory
neurons being dependent upon functional synaptic contact with the olfactory bulb.
Alternatively, this factor may be acting as target-derived growth factor for
olfactory neurons, a role in keeping with its function in spinal motoneurons and
in the nigrostriatal system. Brain-derived neurotrophic factor is implicated in
the trophic support of immature neurons. Ciliary neurotrophic factor is clearly
important in this unique neuronal system but elucidation of its role awaits
further investigation.
PMID- 10188960
TI - Effects of a new C5a receptor antagonist on C5a- and endotoxin-induced
neutropenia in the rat.
AB - A new C5a receptor antagonist, the cyclic peptide Phe-[Orn-Pro-D
cyclohexylalanine-Trp-Arg], (F-[OPdChaWR]), was tested for its ability to
antagonize the neutropenic effects of both C5a and endotoxin in rats. Human
recombinant C5a (2 microg kg(-1) i.v.) caused rapid neutropenia, characterized by
an 83% decrease in circulating polymorphonuclear leukocytes (PMNs) at 5 min.
Administration of F-[OPdChaWR] (0.3-3 mg kg(-1) i.v.), did not affect the levels
of circulating PMNs but, when given 10 min prior to C5a, it inhibited the C5a
induced neutropenia by up to 70%. Administration of E. Coli lipopolysaccharide
(LPS, 1 mg kg(-1) i.v.) also caused neutropenia with an 88% decrease in
circulating PMNs after 30 min. When rats were pretreated with F-[OPdChaWR] (0.3 -
10 mg kg(-1) i.v.) 10 min prior to LPS, there was a dose-dependent antagonism of
the neutropenia caused by LPS, with up to 69% reversal of neutropenia observed 30
min after LPS administration. These findings suggest that C5a receptor
antagonists may have therapeutic potential in the many diseases known to involve
either endotoxin or C5a.
PMID- 10188959
TI - Leukocyte-endothelial cell adhesion: avenues for therapeutic intervention.
PMID- 10188961
TI - Antagonism by acetyl-RYYRIK-NH2 of G protein activation in rat brain preparations
and of chronotropic effect on rat cardiomyocytes evoked by nociceptin/orphanin
FQ.
AB - For the further elucidation of the central functions of nociceptin/orphanin FQ
(noc/OFQ), the endogenous ligand of the G protein-coupled opioid receptor-like
receptor ORL1, centrally acting specific antagonists will be most helpful. In
this study it was found that the hexapeptide acetyl-RYYRIK-NH2 (Ac-RYYRIK-NH2),
described in literature as partial agonist on ORL1 transfected in CHO cells,
antagonizes the stimulation of [35S]-GTPgammaS binding to G proteins by noc/OFQ
in membranes and sections of rat brain. The antagonism of the peptide was
competitive, of high affinity (Schild constant 6.58 nM), and specific for noc/OFQ
in that the stimulation of GTP binding by agonists for the mu-, delta-, and kappa
opioid receptor was not inhibited. The hexapeptide also fully inhibited the
chronotropic effect of noc/OFQ on neonatal rat cardiomyocytes. It is suggested
that Ac-RYYRIK-NH2 may provide a promising starting point for in vivo tests for
antagonism of the action of noc/OFQ and for the further development of highly
active and specific antagonists.
PMID- 10188962
TI - Deficiency of nitric oxide in polycation-induced airway hyperreactivity.
AB - Using a perfused guinea-pig tracheal tube preparation, we investigated the role
of endogenous nitric oxide (NO) in polycation-induced airway hyperreactivity
(AHR) to methacholine. Intraluminal (IL) administration of the NO synthase
inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME; 100 microM) caused a 1.8
fold increase in the maximal contractile response (Emax) to IL methacholine
compared to control, without an effect on the pEC50 (-log10 EC50). The polycation
poly-L-arginine (100 microg ml(-1), IL) similarly enhanced the Emax for
methacholine; however, the pEC50 value was also increased, by one log10 unit. L
NAME had no effect on the enhanced methacholine response of poly-L-arginine
treated airways, while the enhanced agonist response was completely normalized by
the polyanion heparin (25 u ml(-1), IL). In addition, the effect of L-NAME was
fully restored in the poly-L-arginine plus heparin treated airways. The results
indicate that, in addition to enhanced epithelial permeability, a deficiency of
endogenous NO contributes to polycation-induced AHR. The latter finding may
represent a novel mechanism of AHR induced by eosinophil-derived cationic
proteins in allergic asthma.
PMID- 10188963
TI - Cyclo-oxygenase-2 mediates P2Y receptor-induced reactive astrogliosis.
AB - Excessive cyclo-oxygenase-2 (COX-2) induction may play a role in chronic
neurological diseases characterized by inflammation and astrogliosis. We have
previously identified an astroglial receptor for extracellular nucleotides, a P2Y
receptor, whose stimulation leads to arachidonic acid (AA) release, followed, 3
days later, by morphological changes resembling reactive astrogliosis. Since COX
2 may be upregulated by AA metabolites, we assessed a possible role for COX-2 in
P2Y receptor-mediated astrogliosis. A brief challenge of rat astrocytes with the
ATP analogue alpha,beta-methylene ATP (alpha,beta(me)ATP) resulted, 24 h later,
in significantly increased COX-2 expression. The selective COX-2 inhibitor NS-398
completely abolished alpha,beta(me)ATP-induced astrocytic activation.
Constitutive astroglial COX-1 or COX-2 did not play any role in purine-induced
reactive astrogliosis. PGE2, a main metabolite of COX-2, also induced astrocytic
activation. These data suggest that a P2Y receptor mediates reactive astrogliosis
via induction of COX-2. Antagonists selective for this receptor may counteract
excessive COX-2 activation in both acute and chronic neurological diseases.
PMID- 10188964
TI - Modulation of noradrenergic neuronal firing by selective serotonin reuptake
blockers.
AB - Using in vivo extracellular unitary recording, the effect of short term (2-day)
and long-term (21-day) administration of the selective 5-HT reuptake inhibitor
(SSRI) paroxetine (10 mg kg(-1) day(-1), s.c. using osmotic minipumps) was
examined on the spontaneous firing activity of locus coeruleus noradrenergic
neurons. Long-term but not short-term treatment significantly decreased firing
activity. Thus, it appears that enhancing 5-HT neurotransmission by sustained
SSRI administration leads to a reduction of the firing rate of noradrenergic
neurons. The SSRI paroxetine therefore alters the activity of noradrenergic
neurons with a delay that is consistent with its therapeutic action in depression
and panic disorder.
PMID- 10188965
TI - Attenuation of haloperidol-induced catalepsy by a 5-HT2C receptor antagonist.
AB - Atypical neuroleptics produce fewer extrapyramidal side-effects (EPS) than
typical neuroleptics. The pharmacological profile of atypical neuroleptics is
that they have equivalent or higher antagonist affinity for 5-HT2 than for
dopamine D2 receptors. Our aim was to identify which 5-HT2 receptor contributed
to the atypical profile. Catalepsy was defined as rats remaining immobile over a
horizontal metal bar for at least 30 s, 90 min after dosing. Radioligand binding
assays were carried out with homogenates of human recombinant 5-HT2A, 5-HT2B and
5-HT2C receptors expressed in Human Embryo Kidney (HEK293) cells. Haloperidol
(1.13 mg kg(-1) i.p.) induced catalepsy in all experiments. The selective 5
HT2C/2B receptor antagonist, SB-228357 (0.32-10 mg kg(-1) p.o.) significantly
reversed haloperidol-induced catalepsy whereas the 5-HT2A and 5-HT2B receptor
antagonists, MDL-100907 (0.003-0.1 mg kg(-1) p.o.) and SB-215505 (0.1-3.2 mg kg(
1) p.o.) respectively did not reverse haloperidol-induced catalepsy. The data
suggest a role for 5-HT2C receptors in the anticataleptic action of SB-228357.
PMID- 10188966
TI - Rate-dependent blockade of a potassium current in human atrium by the
antihistamine loratadine.
AB - The antihistamine loratadine is widely prescribed for the treatment of symptoms
associated with allergies. Although generally believed to be free of adverse
cardiac effects, there are a number of recent reports suggesting that loratadine
use may be associated with arrhythmias, in particular atrial arrhythmias. Nothing
is known regarding the potassium channel blocking properties of loratadine in
human cardiac cells. Using the whole-cell patch clamp technique, the effects of
loratadine on the transient outward K current (Ito), sustained current (Isus),
and current measured at -100 mV (IK1 and Ins), the major inward and outward
potassium currents present in human atrial myocytes, were examined in order to
provide a possible molecular mechanism for the observed atrial arrhythmias
reported with loratadine use. Loratadine rate-dependently inhibited Ito at
therapeutic concentrations with 10 nM loratadine reducing Ito amplitude at a
pacing rate of 2 Hz by 34.9+/-6.0%. In contrast, loratadine had no effect on
either Isus or current measured at -100 mV. These results may provide a possible
mechanism for the incidences of supraventricular arrhythmias reported with the
use of loratadine.
PMID- 10188967
TI - The effects of specific antibody fragments on the 'irreversible' neurotoxicity
induced by Brown snake (Pseudonaja) venom.
AB - Brown snake (Pseudonaja) venom has been reported to produce 'irreversible' post
synaptic neurotoxicity (Harris & Maltin, 1981; Barnett et al., 1980). A murine
phrenic nerve/diaphragm preparation was used to study the neurotoxic effects of
this venom and pre- and post-synaptic components were distinguished by varying
the temperature and frequency of nerve stimulation. There were no myotoxic
effects and the neurotoxicity proved irreversible by washing alone. The effects
of a new Fab based ovine antivenom have been investigated and proved able to
produce a complete, rapid (< 1 h) reversal of the neurotoxicity induced by Brown
snake venom. A reversal was also possible when the antivenom addition was delayed
for a further 60 min. We believe that this is the first time such a reversal has
been shown.
PMID- 10188968
TI - Canine external carotid vasoconstriction to methysergide, ergotamine and
dihydroergotamine: role of 5-HT1B/1D receptors and alpha2-adrenoceptors.
AB - The antimigraine drugs methysergide, ergotamine and dihydroergotamine (DHE)
produce selective vasoconstriction in the external carotid bed of
vagosympathectomized dogs anaesthetized with pentobarbital and artificially
respired, but the receptors involved have not yet been completely characterized.
Since the above drugs display affinity for several binding sites, including alpha
adrenoceptors and several 5-HT1 and 5-HT2 receptor subtypes, this study has
analysed the mechanisms involved in the above responses. Intracarotid (i.c.)
infusions during 1 min of methysergide (31-310 microg min(-1)), ergotamine (0.56
5.6 microg min(-1)) or DHE (5.6-31 microg min(-1)) dose-dependently reduced
external carotid blood flow (ECBF) by up to 46+/-4, 37+/-4 and 49+/-5%,
respectively. Blood pressure and heart rate remained unchanged. The reductions in
ECBF by methysergide were abolished and even reversed to increases in animals pre
treated with GR127935 (10 microg kg(-1), i.v.). The reductions in ECBF by
ergotamine and DHE remained unchanged in animals pre-treated (i.v.) with prazosin
(300 microg kg(-1)), but were partly antagonized in animals pre-treated with
either GR127935 (10 or 30 microg kg(-1)) or yohimbine (1000 microg kg(-1)). Pre
treatment with a combination of GR127935 (30 microg kg(-1)) and yohimbine (1000
microg kg(-1)) abolished the responses to both ergotamine and DHE. The above
doses of antagonists were shown to produce selective antagonism at their
respective receptors. These results suggest that the external carotid
vasoconstrictor responses to methysergide primarily involve 5-HT1B/1D receptors,
whereas those to ergotamine and DHE are mediated by 5-HT1B/1D receptors as well
as alpha2-adrenoceptors.
PMID- 10188969
TI - Non-specific action of methoxamine on Ito, and the cloned channels hKv 1.5 and Kv
4.2.
AB - The alpha1-adrenoceptor agonist methoxamine acted independently of receptor
activation to reduce Ito and the sustained outward current in rat ventricular
myocytes, and hKv 1.5 and Kv 4.2 cloned K+ channel currents. Two hundred microM
methoxamine reduced Ito by 36% in the presence of 2 microM prazosin, and by 37
and 38% after preincubation of myocytes with either N-ethylmaleimide or
phenoxybenzamine (n=6). The EC50 values at +60 mV for direct reduction of Ito,
hKv 1.5, and Kv 4.2 by methoxamine were 239, 276, and 363 microM, respectively,
with Hill coefficients of 0.87-1.5. Methoxamine accelerated Ito and Kv 4.2
current inactivation in a concentration- and voltage-dependent manner. Apparent
rate constants for methoxamine binding and unbinding gave Kd values in agreement
with EC50 values measured from dose-response relations. The voltage-dependence of
block supported charged methoxamine binding to a putative intracellular site that
sensed approximately 20% of the transmembrane electrical field. In the presence
of methoxamine, deactivating Kv 4.2 tail currents displayed a distinct rising
phase, and were slowed relative to control, such that tail current crossover was
observed. These observations support a dominant mechanism of open channel block,
although closed channel block could not be ruled out. Single-channel data from
hKv 1.5 patches revealed increased closed times with blank sweeps and decreased
burst duration in the presence of drug, and a reduction of mean channel open time
from 1.8 ms in control to 0.4 ms in 500 microM methoxamine. For this channel,
therefore, both open and closed channel block appeared to be important mechanisms
for the action of methoxamine.
PMID- 10188970
TI - Pharmacological diversity between native human 5-HT1B and 5-HT1D receptors sited
on different neurons and involved in different functions.
AB - The releases of [3H]5-hydroxytryptamine ([3H]5-HT) and of endogenous glutamic
acid and their modulation through presynaptic h5-HT1B autoreceptors and h5-HT1D
heteroreceptors have been investigated in synaptosomal preparations from fresh
neocortical samples obtained from patients undergoing neurosurgery. The
inhibition by 5-HT of the K+ (15 mM)-evoked overflow of [3H]5-HT was antagonized
by the 5-HT1B/5-HT1D receptor ligand GR 127935, which was ineffective on its own;
this drug was previously found to behave as a full agonist at the h5-HT1D
heteroreceptor regulating glutamate release. The recently proposed selective h5
HT1B receptor ligand SB-224289 also prevented the effect of 5-HT at the
autoreceptor, being inactive on its own; in contrast, SB-224289, at 1 microM, was
unable to interact with the h5-HT1D heteroreceptor. The inhibitory effect of 5-HT
on the K+-evoked overflow of glutamate was antagonized by the h5-HT1D receptor
ligand BRL-15572; added in the absence of 5-HT the compound was without effect.
BRL-15572 (1 microM) was unable to modify the effect of 5-HT at the autoreceptor
regulating [3H]5-HT release. The selective 5-HT1A receptor antagonist (+)-WAY
100135, previously found to be an agonist at the h5-HT1D heteroreceptor
regulating glutamate release, could not interact with the h5-HT1B autoreceptor
when added at 1 microM. It is concluded that native h5-HT1B and h5-HT1D receptors
exhibit a hitherto unexpected pharmacological diversity.
PMID- 10188971
TI - Effect of prolonged administration of a urinary kinase inhibitor, ebelactone B on
the development of deoxycorticosterone acetate-salt hypertension in rats.
AB - The effect of prolonged administration of a carboxypeptidase Y-like kininase
inhibitor, ebelactone B (EB) (2-ethyl-3, 11-dihydroxy-4, 6, 8, 10, 12-pentamethyl
9-oxo-6-tetradecenoic 1, 3-lactone), on the development of deoxycorticosterone
acetate (DOCA)-salt hypertension was tested. The systolic blood pressure (SBP) of
non-treated 6-week-old Sprague-Dawley strain rats was gradually increased by DOCA
salt treatment from 137+/-2 mmHg (n=11) to 195+/-7 mmHg at 10 weeks of age. With
daily oral administration of lisinopril (5 mg kg(-1), twice a day), which is an
inhibitor of angiotensin converting enzyme, a major kininase in plasma, the
development of hypertension was not suppressed. By contrast, administration of EB
(5 mg kg(-1), twice a day), completely inhibited the development of hypertension
(SBP: 146+/-1 mmHg, n=5, 10 weeks old). The reduced SBP at 10 weeks of age was
equal to the SBP before any treatment (142+/-1 mmHg, n=5). Direct determination
of mean blood pressure (MBP) in conscious, unrestrained rats confirmed that MBP
elevation was completely inhibited by EB. Continuous subcutaneous infusion (5 mg
kg(-1) day(-1)) of HOE140, a bradykinin B2 receptor antagonist, restored the
elevation of SBP, which was suppressed by EB. The weights of left ventricle of
DOCA-salt treated rats 10-weeks-old (0.36+/-0.02 g 100 g body weight(-1), n=11)
was significantly reduced by EB (0.27+/-0.01, n=5), as were the sodium levels in
serum, cerebrospinal fluid and erythrocyte. These findings suggested that EB is
effective in preventing salt-related hypertension presumably by eliminating
sodium retention.
PMID- 10188972
TI - Assessment of the effects of endothelin-1 and magnesium sulphate on regional
blood flows in conscious rats, by the coloured microsphere reference technique.
AB - There is evidence to suggest that magnesium (Mg2+) is beneficial in the treatment
of a number of conditions, including pre-eclampsia and acute myocardial
infarction. The mode of action of Mg2+ in these conditions is not clear, although
the vasodilator properties of Mg2+ are well documented both in vitro and in vivo.
Previously, we demonstrated that i.v. infusion of magnesium sulphate (MgSO4)
alone, or in the presence of vasoconstrictors, caused increases in flow and
conductance in the common carotid, internal carotid and hindquarters vascular
beds, in conscious rats. Therefore, the objective of the present study was to
investigate the regional and subregional changes in haemodynamics in response to
the vasoconstrictor peptide endothelin-1 (ET-1) and MgSO4 in more detail, using
the coloured microsphere reference technique. Infusion of ET-1 and MgSO4 had
similar effects on heart rate and mean arterial pressure as in our previous
study. Infusion of ET-1 caused a rise in mean arterial pressure and a fall in
heart rate, and infusion of MgSO4 returned mean arterial pressure to control
levels with no effect on heart rate. The responses to MgSO4 in the presence of ET
1 showed considerable regional heterogeneity with blood flow increasing (e.g.
skeletal muscle), decreasing (e.g. stomach) or not changing (e.g. kidney). Of
particular interest was the finding that MgSO4 caused increases in flow in the
cerebral and coronary vascular beds. This, and our previous studies, have shown
that MgSO4 can reverse vasoconstriction in a number of vascular beds, and
indicate that this compound may have therapeutic benefit in conditions associated
with vasospasm.
PMID- 10188973
TI - Electrophysiological examination of the effects of sustained flibanserin
administration on serotonin receptors in rat brain.
AB - 5-HT1A receptor agonists have proven to be effective antidepressant medications,
however they suffer from a significant therapeutic lag before depressive symptoms
abate. Flibanserin is a 5-HT1A receptor agonist and 5-HT2A receptor antagonist
developed to possibly induce a more rapid onset of antidepressant action through
its preferential postsynaptic 5-HT1A receptor agonism. Flibanserin antagonized
the effect of microiontophoretically-applied DOI in the medial prefrontal cortex
(mPFC) following 2 days of administration, indicating antagonism of postsynaptic
5-HT2A receptors. This reduction in the effect of locally-applied DOI was no
longer present following 7-day flibanserin administration. Two-day flibanserin
administration only marginally reduced the firing activity of dorsal raphe (DRN)
5-HT neurons. Following 7 days of administration, 5-HT neuronal firing activity
had returned to normal and the somatodendritic 5-HT1A autoreceptors were
desensitized. The responsiveness of postsynaptic 5-HT1A receptors located on CA3
hippocampus pyramidal neurons and mPFC neurons, examined using
microiontophoretically-applied 5-HT and gepirone, was unchanged following a 7-day
flibanserin treatment. As demonstrated by the ability of the 5-HT1A receptor
antagonist WAY 100635 to selectively increase the firing of hippocampal neurons
in 2- and 7-day treated rats, flibanserin enhanced the tonic activation of
postsynaptic 5-HT1A receptors in this brain region. The results suggest that
flibanserin could be a therapeutically useful compound putatively endowed with a
more rapid onset of antidepressant action.
PMID- 10188974
TI - N-Substituted analogues of S-nitroso-N-acetyl-D,L-penicillamine: chemical
stability and prolonged nitric oxide mediated vasodilatation in isolated rat
femoral arteries.
AB - Previous studies show that linking acetylated glucosamine to S-nitroso-N-acetyl
D,L-penicillamine (SNAP) stabilizes the molecule and causes it to elicit
unusually prolonged vasodilator effects in endothelium-denuded, isolated rat
femoral arteries. Here we studied the propanoyl (SNPP; 3 carbon side-chain),
valeryl (SNVP; 5C) and heptanoyl (SNHP; 7C) N-substituted analogues of SNAP (2C),
to further investigate other molecular characteristics that might influence
chemical stability and duration of vascular action of S-nitrosothiols.
Spectrophotometric analysis revealed that SNVP was the most stable analogue in
solution. Decomposition of all four compounds was accelerated by Cu(II) and
cysteine, and neocuproine, a specific Cu(I) chelator, slowed decomposition of
SNHP. Generation of NO from the compounds was confirmed by electrochemical
detection at 37 degrees C. Bolus injections of SNAP (10 microl; 10(-8)-10(-3) M)
into the perfusate of precontracted, isolated rat femoral arteries taken from
adult male Wistar rats (400-500 g), caused concentration-dependent, transient
vasodilatations irrespective of endothelial integrity. Equivalent vasodilatations
induced by SNVP and SNHP were transient in endothelium-intact vessels but failed
to recover to pre-injection pressures at moderate and high concentrations (10(-6)
10(-3) M) in those denuded of endothelium. This sustained effect (> 1 h) was most
prevalent with SNHP and was largely reversed by the NO scavenger, haemoglobin. We
suggest that increased lipophilicity of SNAP analogues with longer sidechains
facilitates their retention by endothelium-denuded vessels; subsequent slow
decomposition within the tissue generates sufficient NO to cause prolonged
vasodilatation. This is a potentially useful characteristic for targeting NO
delivery to areas of endothelial damage.
PMID- 10188975
TI - Bradykinin B1 and B2 receptors, tumour necrosis factor alpha and inflammatory
hyperalgesia.
AB - The effects of BK agonists and antagonists, and other
hyperalgesic/antihyperalgesic drugs were measured (3 h after injection of
hyperalgesic drugs) in a model of mechanical hyperalgesia (the end-point of which
was indicated by a brief apnoea, the retraction of the head and forepaws, and
muscular tremor). DALBK inhibited responses to carrageenin, bradykinin, DABK, and
kallidin. Responses to kallidin and DABK were inhibited by indomethacin or
atenolol and abolished by the combination of indomethacin + atenolol. DALBK or
HOE 140, given 30 min before, but not 2 h after, carrageenin, BK, DABK and
kallidin reduced hyperalgesic responses to these agents. A small dose of DABK+ a
small dose of BK evoked a response similar to the response to a much larger dose
of DABK or BK, given alone. Responses to BK were antagonized by HOE 140 whereas
DALBK antagonized only responses to larger doses of BK. The combination of a
small dose of DALBK with a small dose of HOE 140 abolished the response to BK.
The hyperalgesic response to LPS (1 microg) was inhibited by DALBK or HOE 140 and
abolished by DALBK + HOE 140. The hyperalgesic response to LPS (5 microg) was not
antagonized by DALBK + HOE 140. These data suggest: (a) a predominant role for B2
receptors in mediating hyperalgesic responses to BK and to drugs that stimulate
BK release, and (b) activation of the hyperalgesic cytokine cascade independently
of both B1 and B2 receptors if the hyperalgesic stimulus is of sufficient
magnitude.
PMID- 10188977
TI - Agonist-inverse agonist characterization at CB1 and CB2 cannabinoid receptors of
L759633, L759656, and AM630.
AB - We have tested our prediction that AM630 is a CB2 cannabinoid receptor ligand and
also investigated whether L759633 and L759656, are CB2 receptor agonists. Binding
assays with membranes from CHO cells stably transfected with human CB1 or CB2
receptors using [3H]-CP55940, confirmed the CB2-selectivity of L759633 and
L759656 (CB2/CB1 affinity ratios = 163 and 414 respectively) and showed AM630 to
have a Ki at CB2 receptors of 31.2 nM and a CB2/CB1 affinity ratio of 165. In CB2
transfected cells, L759633 and L759656 were potent inhibitors of forskolin
stimulated cyclic AMP production, with EC50 values of 8.1 and 3.1 nM respectively
and CB1/CB2 EC50 ratios of > 1000 and > 3000 respectively. AM630 inhibited [35S]
GTPgammaS binding to CB2 receptor membranes (EC50 = 76.6 nM), enhanced forskolin
stimulated cyclic AMP production in CB2-transfected cells (5.2 fold by 1 microM),
and antagonized the inhibition of forskolin-stimulated cyclic AMP production in
this cell line induced by CP55940. In CB1-transfected cells, forskolin-stimulated
cyclic AMP production was significantly inhibited by AM630 (22.6% at 1 microM and
45.9% at 10 microM) and by L759633 at 10 microM (48%) but not 1 microM. L759656
(10 microM) was not inhibitory. AM630 also produced a slight decrease in the mean
inhibitory effect of CP55940 on cyclic AMP production which was not statistically
significant. We conclude that AM630 is a CB2-selective ligand that behaves as an
inverse agonist at CB2 receptors and as a weak partial agonist at CB1 receptors.
L759633 and L759656 are both potent CB2-selective agonists.
PMID- 10188976
TI - GABA(B) receptor-mediated stimulation of adenylyl cyclase activity in membranes
of rat olfactory bulb.
AB - Previous studies have shown that GABA(B) receptors facilitate cyclic AMP
formation in brain slices likely through an indirect mechanism involving
intracellular second messengers. In the present study, we have investigated
whether a positive coupling of GABA(B) receptors to adenylyl cyclase could be
detected in a cell-free preparation of rat olfactory bulb, a brain region where
other Gi/Go-coupled neurotransmitter receptors have been found to stimulate the
cyclase activity. The GABA(B) receptor agonist (-)-baclofen significantly
increased basal adenylyl cyclase activity in membranes of the granule cell and
external plexiform layers, but not in the olfactory nerve-glomerular layer. The
adenylyl cyclase stimulation was therefore examined in granule cell layer
membranes. The (-)-baclofen stimulation (pD2=4.53) was mimicked by 3
aminopropylphosphinic acid (pD2=4.60) and GABA (pD2=3.56), but not by (+)
baclofen, 3-aminopropylphosphonic acid, muscimol and isoguvacine. The stimulatory
effect was counteracted by the GABA(B) receptor antagonists CGP 35348 (pA2=4.31),
CGP 55845 A (pA2=7.0) and 2-hydroxysaclofen (pKi=4.22). Phaclofen (1 mM) was
inactive. The (-)-baclofen stimulation was not affected by quinacrine,
indomethacin, nordihydroguaiaretic acid and staurosporine, but was completely
prevented by pertussis toxin and significantly reduced by the alpha subunit of
transducin, a betagamma scavenger. The betagamma subunits of transducin
stimulated the cyclase activity and this effect was not additive with that
produced by (-)-baclofen. In the external plexiform and granule cell layers, but
not in the olfactory nerve-glomerular layer, (-)-baclofen enhanced the adenylyl
cyclase stimulation elicited by the neuropeptide pituitary adenylate cyclase
activating polypeptide (PACAP) 38. Conversely, the adenylyl cyclase activity
stimulated by either forskolin or Ca2+/calmodulin-(Ca2+/CaM) was inhibited by (-)
baclofen in all the olfactory bulb layers examined. These data demonstrate that
in specific layers of rat olfactory bulb activation of GABA(B) receptors enhances
basal and neurotransmitter-stimulated adenylyl cyclase activities by a mechanism
involving betagamma subunits of Gi/Go. This positive coupling is associated with
a widespread inhibitory effect on forskolin- and Ca2+/CaM-stimulated cyclic AMP
formation.
PMID- 10188978
TI - Suppression of nitric oxide synthase and the down-regulation of the activation of
NFkappaB in macrophages by resveratrol.
AB - Resveratrol, naringenin and naringin are naturally occurring flavonoids in grapes
and grapefruits. The anti-inflammatory effects of these flavonoids have been well
documented, but the mechanism is poorly characterized. High concentration of NO
are produced by inducible NO synthase (iNOS) in inflammation, and the prevention
of the expression of iNOS may be an important anti-inflammatory mechanism. In
this study, the effects of these flavonoids on the induction of NO synthase (NOS)
in RAW 264.7 cells activated with bacterial lipopolysaccharide (LPS, 50 ng ml(
1)) were investigated. Resveratrol was found strongly to inhibit NO generation in
activated macrophages, as measured by the amount of nitrite released into the
culture medium, and resveratrol strongly reduced the amount of cytosolic iNOS
protein and steady state mRNA levels. However, the inhibitory abilities of
naringenin were lower, and the inhibitory abilities of naringin were almost
negligible. In electrophoretic mobility shift assays, the activation of NFkappaB
induced by LPS for 1 h was inhibited by resveratrol (30 microM). Furthermore, in
immunoblotting analysis, cells treated with LPS plus resveratrol showed an
inhibition of phosphorylation as well as degradation of IkappaBalpha, and a
reduced nuclear content of NFkappaB subunits. The flavonoids may be of value for
inhibiting the enhanced expression of iNOS in inflammation through down
regulation of NFkappaB binding activity.
PMID- 10188979
TI - ATP- and glutathione-dependent transport of chemotherapeutic drugs by the
multidrug resistance protein MRP1.
AB - The present study was performed to investigate the ability of the multidrug
resistance protein (MRPI) to transport different cationic substrates in
comparison with MDR1-P-glycoprotein (MDR1). Transport studies were performed with
isolated membrane vesicles from in vitro selected multidrug resistant cell lines
overexpressing MDR1 (A2780AD) or MRP1 (GLC4/Adr) and a MRP1-transfected cell line
(S1(MRP)). As substrates we used 3H-labelled derivatives of the hydrophilic
monoquaternary cation N-(4',4'-azo-in-pentyl)-21-deoxy-ajmalinium (APDA), the
basic drug vincristine and the more hydrophobic basic drug daunorubicin. All
three are known MDR1-substrates. MRP1 did not mediate transport of these
substrates per se. In the presence of reduced glutathione (GSH), there was an ATP
dependent uptake of vincristine and daunorubicin, but not of APDA, into GLC4/Adr
and S1(MRP) membrane vesicles which could be inhibited by the MRP1-inhibitor
MK571. ATP- and GSH-dependent transport of daunorubicin and vincristine into
GLC4/Adr membrane vesicles was inhibited by the MRP1-specific monoclonal antibody
QCRL-3. MRP1-mediated daunorubicin transport rates were dependent on the
concentration of GSH and were maximal at concentrations > or = 10 mM. The
apparent KM value for GSH was 2.7 mM. Transport of daunorubicin in the presence
of 10 mM GSH was inhibited by MK571 with an IC50 of 0.4 microM. In conclusion,
these results demonstrate that MRP1 transports vincristine and daunorubicin in an
ATP- and GSH-dependent manner. APDA is not a substrate for MRP1.
PMID- 10188980
TI - An in vitro electrophysiological study on the effects of phenytoin, lamotrigine
and gabapentin on striatal neurons.
AB - We performed intracellular recordings from a rat corticostriatal slice
preparation in order to compare the electrophysiological effects of the classical
antiepileptic drug (AED) phenytoin (PHT) and the new AEDs lamotrigine (LTG) and
gabapentin (GBP) on striatal neurons. PHT, LTG and GBP affected neither the
resting membrane potential nor the input resistance/membrane conductance of the
recorded cells. In contrast, these agents depressed in a dose-dependent and
reversible manner the current-evoked repetitive firing discharge. These AEDs also
reduced the amplitude of glutamatergic excitatory postsynaptic potentials (EPSPs)
evoked by cortical stimulation. However, substantial pharmacological differences
between these drugs were found. PHT was the most effective and potent agent in
reducing sustained repetitive firing of action potentials, whereas LTG and GBP
preferentially inhibited corticostriatal excitatory transmission. Concentrations
of LTG and GBP effective in reducing EPSPs, in fact, produced only a slight
inhibition of the firing activity of these cells. LTG, but not PHT and GBP,
depressed cortically-evoked EPSPs increasing paired-pulse facilitation (PPF) of
synaptic transmission, suggesting that a presynaptic site of action was
implicated in the effect of this drug. Accordingly, PHT and GBP, but not LTG
reduced the membrane depolarizations induced by exogenously-applied glutamate,
suggesting that these drugs preferentially reduce postsynaptic sensitivity to
glutamate released from corticostriatal terminals. These data indicate that in
the striatum PHT, LTG and GBP decrease neuronal excitability by modulating
multiple sites of action. The preferential modulation of excitatory synaptic
transmission may represent the cellular substrate for the therapeutic effects of
new AEDs whose use may be potentially extended to the therapy of
neurodegenerative diseases involving the basal ganglia.
PMID- 10188981
TI - Effects of angiotensin II receptor blockade on proximal fluid uptake in the rat
kidney.
AB - Angiotensin II has a well described dose-dependent biphasic action on proximal
tubule fluid uptake, although the concentration and effect of endogenous luminal
angiotensin II remain controversial. Shrinking split-droplet micropuncture was
used to examine the fluid uptake in response to the luminal application of three
AT1 antagonists (losartan, EXP3174, candesartan). Addition of losartan at 10(-8)
M decreased fluid uptake rate (Jva) by 17.5+/-2.2% (P<0.05). Luminal addition of
EXP3174 at concentrations between 10(-9)-10(-5) M caused a dose-dependent
decrease in fluid uptake, with a maximum decrease of 41.0+/-9.5% (P<0.01) at 10(
6) M. Candesartan also decreased fluid uptake, by 21.9+/-4.9% (P<0.05) at 10(-8)
M and 23.6+/-5.5% (P<0.05) at 10(-5) M. All three antagonists at a low
concentration (10(-8) M) decreased fluid uptake. EXP3174 and candesartan at a
higher concentration (10(-5) M) also decreased fluid uptake in contrast to the
previously reported effect of losartan. We conclude that the endogenous
concentration of antiotensin II in the proximal luminal fluid is low and exerts a
stimulatory effect on fluid absorption. Losartan at concentrations greater than
10(-6) M may have a non-selective action on fluid uptake.
PMID- 10188982
TI - Pharmacological evidence that inducible nitric oxide synthase is a mediator of
delayed preconditioning.
AB - Brief periods of myocardial ischaemia preceding a subsequent more prolonged
ischaemic period 24-72 h later confer protection against myocardial infarction
('delayed preconditioning' or the 'second window' of preconditioning). In the
present study, we examined the effects of pharmacological modifiers of inducible
nitric oxide synthase (iNOS) induction and activity on delayed protection
conferred by ischaemic preconditioning 48 h later in an anaesthetized rabbit
model of myocardial infarction. Rabbits underwent a myocardial preconditioning
protocol (four 5 min coronary artery occlusions) or were sham-operated. Forty
eight hours later they were subjected to a sustained 30 min coronary occlusion
and 120 min reperfusion. Infarct size was determined with triphenyltetrazolium
staining. In rabbits receiving no pharmacological intervention, the percentage of
myocardium infarcted within the risk zone was 43.9+5.0% in sham-operated animals
and this was significantly reduced 48 h after ischaemic preconditioning with four
5 min coronary occlusions to 18.5+5.6% (P<0.01). Administration of the iNOS
expression inhibitor dexamethasone (4 mg kg(-1) i.v) 60 min before ischaemic
preconditioning completely blocked the infarct-limiting effect of ischaemic
preconditioning (infarct size 48.6+/-6.1%). Furthermore, administration of
aminoguanidine (300 mg kg(-1), s.c.), a relatively selective inhibitor of iNOS
activity, 60 min before sustained ischaemia also abolished the delayed protection
afforded by ischaemic preconditioning (infarct size 40.0+/-6.0%). Neither
aminoguanidine nor dexamethasone per se had significant effect on myocardial
infarct size. Myocardial risk zone volume during coronary ligation, a primary
determinant of infarct size in this non-collateralized species, was not
significantly different between intervention groups. There were no differences in
systolic blood pressure, heart rate, arterial blood pH or rectal temperature
between groups throughout the experimental period. These data provide
pharmacological evidence that the induction of iNOS, following brief periods of
coronary occlusion, is associated with increased myocardial tolerance to
infarction 48 h later.
PMID- 10188983
TI - Endothelium-derived relaxing, contracting and hyperpolarizing factors of
mesenteric arteries of hypertensive and normotensive rats.
AB - Differences in the acetylcholine (ACh)-induced endothelium-dependent relaxation
and hyperpolarization of the mesenteric arteries of Wistar Kyoto rats (WKY) and
stroke-prone spontaneously hypertensive rats (SHRSP) were studied. Relaxation was
impaired in preparations from SHRSP and tendency to reverse the relaxation was
observed at high concentrations of ACh in these preparations. Relaxation was
partly blocked by NG-nitro-L-arginine (L-NOARG, 100 microM) and, in the presence
of L-NOARG, tendency to reverse the relaxation was observed in response to higher
concentrations of ACh, even in preparations from WKY. The relaxation remaining in
the presence of L-NOARG was also smaller in preparations from SHRSP. The tendency
to reverse the relaxation observed at higher concentrations of ACh in
preparations from SHRSP or WKY in the presence of L-NOARG were abolished by
indomethacin (10 microM). Elevating the K+ concentration of the incubation medium
decreased relaxation in the presence of both indomethacin and L-NOARG. Relaxation
in the presence of L-NOARG and indomethacin was reduced by the application of
both apamin (5 microM) and charybdotoxin (0.1 microM). This suggests that the
relaxation induced by ACh is brought about by both endothelium-derived relaxing
factor (EDRF, nitric oxide (NO)) and hyperpolarizing factor (EDHF), which
activates Ca2+-sensitive K+ channels. Electrophysiological measurement revealed
that ACh induced endothelium-dependent hyperpolarization of the smooth muscle of
both preparations in the presence of L-NOARG and indomethacin; the
hyperpolarization being smaller in the preparation from SHRSP than that from WKY.
These results suggest that the release of both NO and EDHF is reduced in
preparations from SHRSP. In addition, indomethacin-sensitive endothelium-derived
contracting factor (EDCF) is released from both preparations; the release being
increased in preparations from SHRSP.
PMID- 10188984
TI - Vasorelaxation and inhibition of the voltage-operated Ca2+ channels by FK506 in
the porcine coronary artery.
AB - Using fura-2 fluorometry, the effects of FK506, an immunosuppressant, on changes
in cytosolic Ca2+ concentrations ([Ca2+]i) and tension were investigated in
porcine coronary arterial strips. The effects of FK506 on the activity of voltage
operated Ca2+ channels were examined by applying a whole cell patch clamp to the
isolated smooth muscle cells of porcine coronary artery. FK506 inhibited the
sustained increases in both [Ca2+]i and tension induced by 118 mM K+
depolarization and 100 nM U46619 in a concentration-dependent manner (1-30
microM). The extent of inhibition of the K+-induced contraction was greater than
that of the U46619-induced contraction. The increases in [Ca2+]i and tension
induced by histamine and endothelin- in the presence of extracellular Ca2+ were
also inhibited by 10 microM FK506. FK506 (10 microM) had no effect on Ca2+
release induced by caffeine or by histamine in the Ca2+-free solution. FK506 (10
microM) had no effect on the [Ca2+]i-tension relationships of the contractions
induced by cumulative increases of extracellular Ca2+ during K+ depolarization or
stimulation with U46619. In the patch clamp experiments, FK506 (30 microM)
partially inhibited the inward current induced by depolarization pulse from -80
mV to 0 mV. In conclusion, FK506 induces arterial relaxation by decreasing
[Ca2+]i mainly due to the inhibition of the L-type Ca2+ channels, with no effect
on the Ca2+ sensitivity of the contractile apparatus.
PMID- 10188985
TI - Effects of vitamin C and of a cell permeable superoxide dismutase mimetic on
acute lipoprotein induced endothelial dysfunction in rabbit aortic rings.
AB - Low density lipoprotein (LDL) inhibits endothelium-dependent relaxation. The
mechanism is uncertain, but increased production of superoxide anion O2- with
inactivation of endothelium-derived NO and formation of toxic free radical
species have been implicated. We investigated effects of the cell permeable
superoxide dismutase mimetic manganese (III) tetrakis (1-methyl-4-pyridyl)
porphyrin (MnTMPyP), the free radical scavenger vitamin C and arginine (which may
reduce O2- formation) on acute LDL-induced endothelial dysfunction in rabbit
aortic rings, using LDL prepared by ultracentrifugation of plasma from healthy
men and aortic rings from New Zealand white rabbits. LDL (150 microg protein ml(
1) for 20 min) markedly inhibited relaxation of aortic rings (in Krebs' solution
at 37 degrees C and pre-constricted to 80% maximum tension with noradrenaline) to
acetylcholine 82+/-10% (mean percentage difference between sum of relaxations
after each concentration of acetylcholine in the presence and absence of LDL, +/
s.e.mean, n=26, P<0.001) but not to the endothelium-independent agonist
nitroprusside. MnTMPyP (10 microM) reduced inhibitory effects of LDL from 124+/
27 to 56+/-17% (n=6, P<0.05). Vitamin C (1 mM) reduced inhibitory effects of LDL
from 59+/-8 to 22+/-5% (n=6, P<0.05). Inhibitory effects of LDL were similar in
the absence or presence of arginine (84+/-12 vs 79+/-16%, n=14, P=0.55). Effects
of L-arginine (10 mM) did not differ significantly from those of D-arginine (10
mM). Acute (20 min) exposure of aortic rings to LDL impairs endothelium-dependent
relaxation which can be partially restored by MnTMPyP and vitamin C. This is
consistent with LDL causing increased O2- generation.
PMID- 10188986
TI - Roles of threonine 192 and asparagine 382 in agonist and antagonist interactions
with M1 muscarinic receptors.
AB - Conserved amino acids, such as Thr in transmembrane domains (TM) V and Asn in TM
VI of muscarinic receptors, may be important in agonist binding and/or receptor
activation. In order to determine the functional roles of Thr192 and Asn382 in
human M1 receptors in ligand binding and receptor activation processes, we
created and characterized mutant receptors with Thr192 or Asn382 substituted by
Ala. HM1 wild-type (WT) and mutant receptors [HM1(Thr192Ala) and HM1(Asn382Ala)]
were stably expressed in A9 L cells. The Kd values for 3H-(R)-QNB and Ki values
for other classical muscarinic antagonists were similar at HM1(WT) and
HM1(Thr192Ala) mutant receptors, yet higher at HM1(Asn382Ala) mutant receptors.
Carbachol exhibited lower potency and efficacy in stimulating PI hydrolysis via
HM1(Thr192Ala) mutant receptors, and intermediate agonist activity at the
HM1(Asn382Ala) mutant receptors. The Asn382 residue in TM VI but not the Thr192
residue in TM V of the human M1 receptor appears to participate directly in
antagonist binding. Both Thr192 and Asn382 residues are involved differentially
in agonist binding and/or receptor activation processes, yet the Asn382 residue
is less important than Thr192 in agonist activation of M1 receptors. Molecular
modelling studies indicate that substitution of Thr192 or Asn382 results in the
loss of hydrogen-bond interactions and changes in the agonist binding mode
associated with an increase in hydrophobic interactions between ligand and
receptor.
PMID- 10188987
TI - Inhibition of inducible nitric oxide synthase by beta-lapachone in rat alveolar
macrophages and aorta.
AB - Beta-lapachone, a plant product, has been shown to be a novel inhibitor of DNA
topoisomerase. In this study, we performed experiments to examine the effects of
beta-lapachone on lipopolysaccharide (LPS)-induced inducible nitric oxide (NO)
synthase (iNOS) in rat alveolar macrophages and aortic rings. In alveolar
macrophages, incubation with LPS (10 microg ml(-1)) for various time intervals
resulted in a significant increase in nitrite production and iNOS protein
synthesis, that was inhibited by coincubation with beta-lapachone (1-4.5 microM)
without any cytotoxic effects. However, addition of beta-lapachone after
induction of NO synthase by LPS failed to affect the nitrite production.
Treatment with LPS (10 microg ml(-1)) for 6 h resulted in significant expression
of mRNA for iNOS which was significantly inhibited in the presence of beta
lapachone (3 microM) in alveolar macrophages. In endothelium-intact rings of
thoracic aorta, beta-lapachone (1 and 3 microM) markedly inhibited the
hypocontractility to phenylephrine in aortic rings treated with LPS (10 microg
ml(-1)) for 4 h. When beta-lapachone was added 3 h after LPS into the medium, the
contractions evoked by phenylephrine were not significantly different in the
presence or absence of beta-lapachone. Treatment with LPS (10 microg ml(-1)) for
4 h resulted in a significant increase in iNOS protein synthesis which was
inhibited in the presence of beta-lapachone (3 microM), but did not affect the
constitutive (endothelial and neuronal) NOS forms in aortic rings. These results
indicate that beta-lapachone is capable of inhibiting expression and function of
iNOS in rat alveolar macrophages and aortic rings. It is considered that beta
lapachone can be developed as a potential anti-inflammatory agent in the future.
PMID- 10188988
TI - Inhibitory effects of aprindine on the delayed rectifier K+ current and the
muscarinic acetylcholine receptor-operated K+ current in guinea-pig atrial cells.
AB - In order to clarify the mechanisms by which the class Ib antiarrhythmic drug
aprindine shows efficacy against atrial fibrillation (AF), we examined the
effects of the drug on the repolarizing K+ currents in guinea-pig atrial cells by
use of patch-clamp techniques. We also evaluated the effects of aprindine on
experimental AF in isolated guinea-pig hearts. Aprindine (3 microM) inhibited the
delayed rectifier K+ current (IK) with little influence on the inward rectifier
K+ current (IK1) or the Ca2+ current. Electrophysiological analyses including the
envelope of tails test revealed that aprindine preferentially inhibits IKr
(rapidly activating component) but not IKs (slowly activating component). The
muscarinic acetylcholine receptor-operated K+ current (IK.ACh) was activated by
the extracellular application of carbachol (1 microM) or by the intracellular
loading of GTPgammaS. Aprindine inhibited the carbachol- and GTPgammaS-induced
IK.ACh with the IC50 values of 0.4 and 2.5 microM, respectively. In atrial cells
stimulated at 0.2 Hz, aprindine (3 microM) per se prolonged the action potential
duration (APD) by 50+/-4%. The drug also reversed the carbachol-induced action
potential shortening in a concentration-dependent manner. In isolated hearts,
perfusion of carbachol (1 microM) shortened monophasic action potential (MAP) and
effective refractory period (ERP), and lowered atrial fibrillation threshold.
Addition of aprindine (3 microM) inhibited the induction of AF by prolonging MAP
and ERP. We conclude the efficacy of aprindine against AF may be at least in part
explained by its inhibitory effects on IKr and IK.ACh.
PMID- 10188989
TI - Modulation of ATP-responses at recombinant rP2X4 receptors by extracellular pH
and zinc.
AB - The modulatory effects of extracellular H+ and Zn2+ were tested against ATP
responses at rat P2X4 (rP2X4) receptors expressed in Xenopus oocytes under
voltage-clamp conditions. ATP (0.1-100 microM, at pH 7.5), evoked inward currents
via rP2X4 receptors (EC50 value, 4.1+/-0.98 microM; nH, 1.2+/-0.1). ATP potency
was reduced 2 fold, at pH 6.5, without altering maximal activity. ATP potency was
reduced by a further 4 fold, at pH 5.5, and the maximal activity of ATP was also
reduced. Alkaline conditions (pH 8.0) had no effect on ATP-responses. Zn2+ (100
nM - 10 microM) potentiated ATP-responses at the rP2X4 receptor by 2 fold,
whereas higher concentrations (30 microM - 1 mM) inhibited ATP-responses. Zn2+
potentiation was due to an increase in ATP potency, whereas its inhibitory action
was due to a reduction in ATP efficacy. Zn2+ modulation of ATP-responses was pH
dependent. At pH 6.5, the bell-shaped curve for Zn2+ was shifted to the right by
1 log unit. At pH 5.5, Zn2+ potentiation was abolished and its inhibitory effect
reduced considerably. Suramin (50 microM) also potentiated ATP-responses at rP2X4
receptors. Neither H+ (pH 6.5 and 5.5), Zn2+ (10-100 microM) or a combination of
both failed to reveal an inhibitory action of suramin at rP2X4 receptors. In
conclusion, H+ and Zn2+ exerted opposite effects on the rP2X4 receptor by
lowering and raising agonist potency, respectively. H+ (> or = 3 microM) and Zn2+
(> or = 30 microM) also reduces agonist efficacy by lowering the number of rP2X4
receptors available for activation. The striking differences between the
modulatory actions of H+ and Zn2+ at rP2X4 and rP2X2 receptors are discussed.
PMID- 10188991
TI - Roles of oxygen radicals and elastase in citric acid-induced airway constriction
of guinea-pigs.
AB - Antioxidants attenuate noncholinergic airway constriction. To further investigate
the relationship between tachykinin-mediated airway constriction and oxygen
radicals, we explored citric acid-induced bronchial constriction in 48 young
Hartley strain guinea-pigs, divided into six groups: control; citric acid;
hexa(sulphobutyl)fullerenes + citric acid; hexa(sulphobutyl)fullerenes +
phosphoramidon + citric acid; dimethylthiourea (DMTU) + citric acid; and DMTU +
phosphoramidon + citric acid. Hexa(sulphobutyl)fullerenes and DMTU are scavengers
of oxygen radicals while phosphoramidon is an inhibitor of the major degradation
enzyme for tachykinins. Animals were anaesthetized, paralyzed, and artificially
ventilated. Each animal was given 50 breaths of 4 ml saline or citric acid
aerosol. We measured dynamic respiratory compliance (Crs), forced expiratory
volume in 0.1 (FEV0.1), and maximal expiratory flow at 30% total lung capacity
(Vmax30) to evaluate the degree of airway constriction. Citric acid, but not
saline, aerosol inhalation caused marked decreases in Crs, FEV0.1 and Vmax30,
indicating marked airway constriction. This constriction was significantly
attenuated by either hexa(sulphobutyl)fullerenes or by DMTU. In addition,
phosphoramidon significantly reversed the attenuating action of
hexa(sulphobutyl)fullerenes, but not that of DMTU. Citric acid aerosol inhalation
caused increases in both lucigenin- and t-butyl hydroperoxide-initiated
chemiluminescence counts, indicating citric acid-induced increase in oxygen
radicals and decrease in antioxidants in bronchoalveolar lavage fluid. These
alterations were significantly suppressed by either hexa(sulphobutyl)fullerenes
or DMTU. An elastase inhibitor eglin-c also significantly attenuated citric acid
induced airway constriction, indicating the contributing role of elastase in this
type of constriction. We conclude that both oxygen radicals and elastase play an
important role in tachykinin-mediated, citric acid-induced airway constriction.
PMID- 10188990
TI - Inhibition of poly(ADP-ribose) synthetase (PARS) and protection against
peroxynitrite-induced cytotoxicity by zinc chelation.
AB - Peroxynitrite, a potent oxidant formed by the reaction of nitric oxide and
superoxide causes thymocyte necrosis, in part, via activation of the nuclear
enzyme poly(ADP-ribose) synthetase (PARS). The cytotoxic PARS pathway initiated
by DNA strand breaks and excessive PARS activation has been shown to deplete
cellular energy pools, leading to cell necrosis. Here we have investigated the
effect of tetrakis-(2-pyridylmethyl)-ethylenediamine (TPEN) a heavy metal
chelator on peroxynitrite-induced cytotoxicity. TPEN (10 microM) abolished cell
death induced by authentic peroxynitrite (25 microM) and the peroxynitrite
generating agent 3-morpholinosidnonimine (SIN-1, 250 microM). Preincubation of
TPEN with equimolar Zn2+ but not Ca2+ or Mg2+ blocked the cytoprotective effect
of the chelator. TPEN (10 microM) markedly reduced the peroxynitrite-induced
decrease of mitochondrial transmembrane potential, secondary superoxide
production and mitochondrial membrane damage, indicating that it acts proximal to
mitochondrial alterations. Although TPEN (1 - 300 microM) did not scavenge
peroxynitrite, it inhibited PARS activation in a dose-dependent manner. The
cytoprotective effect of TPEN is only partly mediated via PARS inhibition, as the
chelator also protected PARS-deficient thymocytes from peroxynitrite-induced
death. While being cytoprotective against peroxynitrite-induced necrotic death,
TPEN (10 microM), similar to other agents that inhibit PARS, enhanced apoptosis
(at 5-6 h after exposure), as characterized by phosphatydilserine exposure,
caspase activation and DNA fragmentation. In conclusion, the current data
demonstrate that TPEN, most likely by zinc chelation, exerts protective effects
against peroxynitrite-induced necrosis. Its effects are, in part, mediated by
inhibition of PARS.
PMID- 10188992
TI - Effects of vasopressin on the sympathetic contraction of rabbit ear artery during
cooling.
AB - In order to analyse the effects of arginine-vasopressin on the vascular
contraction to sympathetic nerve stimulation during cooling, the isometric
response of isolated, 2-mm segments of the rabbit central ear (cutaneous) artery
to electrical field stimulation (1-8 Hz) was recorded at 37 and 30 degrees C.
Electrical stimulation (37 degrees C) produced frequency-dependent arterial
contraction, which was reduced at 30 degrees C and potentiated by vasopressin (10
pM, 100 pM and 1 nM). This potentiation was greater at 30 than at 37 degrees C
and was abolished at both temperatures by the antagonist of vasopressin V1
receptors d(CH2)5 Tyr(Me)AVP (100 nM). Desmopressin (1 microM) did not affect the
response to electrical stimulation. At 37 degrees C, the vasopressin-induced
potentiation was abolished by the purinoceptor antagonist PPADS (30 microM),
increased by phentolamine (1 microM) or prazosin (1 microM) and not modified by
yohimbine (1 microM), whilst at 30 degrees C, the potentiation was reduced by
phentolamine, yohimbine or PPADS, and was not modified by prazosin. The Ca2+
channel blockers, verapamil (10 microM) and NiCl2 (1 mM), abolished the
potentiating effects of vasopressin at 37 degrees C whilst verapamil reduced and
NiCl2 abolished this potentiation at 30 degrees C. The inhibitor of nitric oxide
synthesis, L-NOARG (100 microM), or endothelium removal did not modify the
potentiation by vasopressin at 37 and 30 degrees C. Vasopressin also increased
the arterial contraction to the alpha2-adrenoceptor agonist BHT-920 (10 microM)
and to ATP (2 mM) at 30 and 37 degrees C, but it did not modify the contraction
to noradrenaline (1 microM) at either temperature. These results suggest that in
cutaneous (ear) arteries, vasopressin potentiaties sympathetic vasoconstriction
to a greater extent at 30 than at 37 degrees C by activating vasopressin V1
receptors and Ca2+ channels at both temperatures. At 37 degrees C, the
potentiation appears related to activation of the purinoceptor component and, at
30 degrees C, to activation of both purinoceptor and alpha2-adrenoceptor
components of the sympathetic response.
PMID- 10188994
TI - Mode of action of ICS 205,930, a novel type of potentiator of responses to
glycine in rat spinal neurones.
AB - The effect of a novel potentiator of glycine responses, ICS 205,930, was studied
by whole-cell recordings from spinal neurones, and compared with that of other
known potentiators, in an attempt to differentiate their sites of action. The
ability of ICS 205,930 (0.2 microM) to potentiate glycine responses persisted in
the presence of concentrations of Zn2+ (5-10 microM) that were saturating for the
potentiating effect of this ion. Preincubation with 10 microM Zn2+ before
application of glycine plus Zn2+ had an inhibitory effect, which did not result
from Zn2+ entry into the neurone, since it persisted with either 10 mM internal
EGTA or 10 microM internal Zn2+. To test whether the potentiating effects of ICS
205,930 and Zn2+ interact, both compounds were applied without preincubation. The
potentiating effect of ICS 205,930 was similar for responses to glycine and for
responses to glycine plus Zn2+, provided the concentrations of agonist were
adjusted so as to induce control responses of identical amplitudes. ICS 205,930
remained able to potentiate glycine responses in the presence of ethanol (200
mM). ICS 205,930 also retained its potentiating effect in the presence of the
anaesthetic propofol (30 90 microM), which strongly potentiated glycine responses
but, in contrast with ICS 205,930, also markedly increased the resting
conductance. The anticonvulsant chlormethiazole (50-100 microM) neither
potentiated glycine responses nor prevented the effect of ICS 205,930, even
though it increased the resting conductance and potentiated GABA(A) responses.
The mechanism of action of ICS 205,930 appears to be different from those by
which Zn2+, propofol or ethanol potentiate glycine responses.
PMID- 10188993
TI - Hyperbaric oxygen increases plasma exudation in rat trachea: involvement of
nitric oxide.
AB - This study investigates the microvascular permeability changes in tracheal tissue
of rats exposed to hyperbaric oxygen (HBO). Rats, following exposure to HBO or
ambient air (control animals) for 1.5, 3 and 6 h, were prepared for recording of
nitric oxide exhaled (FENO) in air using a chemiluminescence analyser. The level
of FENO was not statistically different in the two groups. Plasma exudation,
evaluated by measuring the leakage of Evans blue (EB) dye into the tracheal
tissue, was significantly elevated (48, 86 and 105% at 1.5, 3 and 6 h,
respectively) in HBO-treated rats. Plasma exudation in the trachea of control
rats was significantly increased (42%, P<0.05) by NG-nitro-L-arginine methyl
ester (L-NAME), whereas it was significantly reduced (31%, P<0.05) in rats
exposed to HBO for 3 h. N-acetylcysteine (NAC) and flunisolide significantly
prevented the increase in plasma leakage in HBO-treated rats. In contrast,
indomethacin was devoid of anti-exudative activity in these experiments. Western
immunoblot showed a significant increase in the level of inducible nitric oxide
synthase (iNOS) protein in the tracheal homogenates of HBO-treated rats, as
compared to basal levels. These results indicate that nitric oxide (NO) is
involved in the maintenance of microvascular permeability in tracheal tissue of
rats. The protective effect observed with the steroid seems to support this
hypothesis. Furthermore, the beneficial action of NAC underlines that reactive
oxygen species participate in the microvascular permeability changes observed in
tracheal tissue of rats exposed to HBO.
PMID- 10188995
TI - Signalling by CXC-chemokine receptors 1 and 2 expressed in CHO cells: a
comparison of calcium mobilization, inhibition of adenylyl cyclase and
stimulation of GTPgammaS binding induced by IL-8 and GROalpha.
AB - The effect of interleukin-8 (IL-8) and growth-related oncogene alpha (GROalpha)
on [35S]-guanosine 5'-O-(3-thiotriphosphate) ([35S]GTPgammaS) binding, forskolin
stimulated cyclic AMP accumulation and cytosolic calcium concentration were
determined in recombinant CHO cells expressing HA-tagged CXC-chemokine receptors
1 and 2 (CXCR1 and CXCR2). Radioligand binding assays confirmed that the binding
profiles of the recombinant receptors were similar to those of the native
proteins. IL-8 displaced [125I]-IL-8 binding to CXCR1 and CXCR2 with pKi values
of 8.89+/-0.05 and 9.27+/-0.03, respectively. GROalpha, a selective CXCR2 ligand,
had a pKi value of 9.66+/-0.39 at CXCR2 but a pKi>8 at CXCR1. Calcium
mobilization experiments were also consistent with previous reports on native
receptors. Activation of both receptors resulted in stimulation of [35S]GTPgammaS
binding and inhibition of adenylyl cyclase. A comparison of the functional data
at CXCRI showed that a similar potency order (IL-8> >GROalpha) was obtained in
all three assays. However, at CXCR2 whilst the potency orders for calcium
mobilization and inhibition of adenylyl cyclase were similar (IL-8 > or =
GROalpha), the order was reversed for stimulation of [35S]GTPgammaS binding
(GROalpha > IL-8). All of the functional responses at both receptors were
inhibited by pertussis toxin (PTX), suggesting coupling to a Gi/Go protein.
However, the calcium mobilization induced by IL-8 at CXCR1 was not fully
inhibited by PTX, suggesting an interaction with a G-protein of the Gq family.
Our results with pertussis toxin also suggested that, in the [35S]GTPgammaS
binding assay, CXCR1 displays some constitutive activity. Thus, we have
characterized the binding and several functional responses at HA-tagged CXCRs 1
and 2 and have shown that their pharmacology agrees well with that of the native
receptors. We also have preliminary evidence that CXCR1 displays constitutive
activity in our cell line and that CXCR2 may traffic between different PTX
sensitive G-proteins.
PMID- 10188996
TI - Functional and molecular biological evidence for a possible beta3-adrenoceptor in
the human detrusor muscle.
AB - The possible existence of a beta3-adrenergic receptor (beta3-AR) in the human
detrusor muscle was investigated by in vitro functional studies and analysis of
mRNA expression. Isoprenaline, noradrenaline and adrenaline each produced a
concentration-dependent relaxation of the human detrusor. The rank order for
their relaxing potencies was isoprenaline (pD2 6.37+/-0.07) > or = noradrenaline
(pD2 6.07+/-0.12) > or = adrenaline (pD2 5.88< or =0.11). Neither dobutamine
(beta1- and beta2-AR agonist) nor procaterol (beta2-AR agonist) produced any
significant relaxation at concentrations up to 10(-5) M. BRL37344A, CL316243 and
CGP-12177A (beta3-AR agonists), relaxed the preparations significantly at
concentrations higher than 10(-6) M. The pD2 values for BRL37344A, CL316243 and
CGP-12177A were 6.42+/-0.25, 5.53+/-0.09 and 5.74+/-0.14, respectively. CGP
20712A (10(-7) - 10(-5) M), a beta1-AR antagonist, did not affect the
isoprenaline-induced relaxation. On the other hand, ICI-118,551, a beta2-AR
antagonist, produced a rightward parallel shift of the concentration-relaxation
curve for isoprenaline only at the highest concentration used (10(-5) > M) and
its pKB value was 5.71+/-0.19. Moreover, SR58894A (10(-7) - 10(-5) M), a beta3-AR
antagonist, caused a rightward shift of the concentration-relaxation curve for
isoprenaline in a concentration-dependent manner. The pA2 value and slope
obtained from Schild plots were 6.24+/-0.20 and 0.68+/-0.31. The beta1-, beta2-
and beta3-AR mRNAs were all positively expressed in detrusor smooth muscle
preparations in a reverse transcription polymerase chain reaction assay. In
conclusion, the present results provide the first evidence for the existence of
the beta3-AR subtype in the human detrusor. They also suggest that the relaxation
induced by adrenergic stimulation of the human detrusor is mediated mainly
through beta3-AR activation.
PMID- 10188997
TI - The subtype 2 of angiotensin II receptors and pressure-natriuresis in adult rat
kidneys.
AB - The present work examined the effects of the subtype 2 of angiotensin II (AT2)
receptors on the pressure-natriuresis using a new peptide agonist, and the
possible involvement of cyclic guanosine 3', 5' monophosphate (cyclic GMP) in
these effects. In adult anaesthetized rats (Inactin, 100 mg kg(-1), i.p.)
deprived of endogenous angiotensin II by angiotensin converting enzyme inhibition
(quinapril, 10 mg kg(-1), i.v.), T2-(Ang II 4-8)2 (TA), a highly specific AT2
receptor agonist (5, 10 and 30 microg kg(-1) min(-1), i.v.) or its solvent was
infused in four groups. Renal functions were studied at renal perfusion pressures
(RPP) of 90, 110 and 130 mmHg and urinary cyclic GMP excretion when RPP was at
130 mmHg. The effects of TA (10 microg kg(-1) min(-1)) were reassessed in animals
pretreated with PD 123319 (PD, 50 microg kg(-1) min(-1), i.v.), an AT2 receptor
antagonist and the action of the same dose of PD alone was also determined.
Increases in RPP from 90 to 130 mmHg did not change renal blood flow (RBF) but
induced 8 and 15 fold increases in urinary flow and sodium excretion
respectively. The 5 microg kg(-1) min(-1) dose of TA was devoid of action. The 10
and 30 microg kg(-1) min(-1) doses did not alter total RBF and glomerular
filtration rate, but blunted pressure-diuresis and natriuresis relationships.
These effects were abolished by PD. TA decreased urinary cyclic GMP excretion.
After pretreatment with PD, this decrease was reversed to an increase which was
also observed in animals receiving PD alone. In conclusion, renal AT2 receptors
oppose the sodium and water excretion induced by acute increases in blood
pressure and this action cannot be directly explained by changes in cyclic GMP.
PMID- 10188999
TI - Magnesium the forgotten cation.
PMID- 10188998
TI - Beta-adrenoceptor agonist stimulation of pulmonary nitric oxide production in the
rabbit.
AB - Nitric oxide (NO) is continuously produced in the lung and is present in exhaled
air. We examined the effect of beta-adrenoceptor stimulation on the production of
pulmonary NO in rabbits. Exhaled NO was measured by chemiluminescence in
anaesthetized and mechanically ventilated rabbits and in buffer-perfused rabbit
lungs. Intravenous infusions of adrenaline (0.1-10 microg kg(-1) min(-1))
elicited dose-dependent increases in exhaled NO. The increases in exhaled NO
comprised an initial peak followed by a lower plateau level. The increase in
exhaled NO was inhibited by propranolol (1 mg kg(-1)) but not by phentolamine (1
mg kg(-1)). Prenalterol, a beta1-adrenoceptor agonist, and terbutaline, a beta2
adrenoceptor agonist, also caused dose-dependent increases in exhaled NO.
However, prenalterol was >100 times more potent than terbutaline. Infusions of
forskolin (0.01-0.03 micromol kg(-1) min(-1)), an adenylate cyclase stimulator,
elicited dose-dependent decreases in blood pressure and concomitant increases in
heart rate but caused no alterations in exhaled NO. Nimodipine, a L-type calcium
channel blocker, antagonized the increases in exhaled NO in response to
prenalterol infusions. The increases in exhaled NO in response to adrenaline and
prenalterol were also present in blood-free, buffer perfused lungs during
constant-flow conditions. These results demonstrate that pulmonary nitric oxide
production can be enhanced by beta-adrenoceptor stimulation. Furthermore, the
results indicate that the beta-adrenergic stimulation of pulmonary NO production
is not critically dependent on cyclic AMP formation but may require intact
calcium-channels.
PMID- 10189000
TI - Are coronary patients at higher risk with digoxin therapy? An ongoing
controversy.
AB - Previous reports have yielded contradictory conclusions regarding the safety of
digoxin therapy in patients with acute myocardial infarction. The purpose of our
study was to determine whether digoxin therapy is associated with increased
mortality in patients with chronic coronary artery disease. We analyzed data from
8173 patients who were screened for participation in the Bezafibrate Infarction
Prevention (BIP) trial and who survived an acute myocardial infarction at least 6
months prior to the study. Three-year overall mortality of the 451 (15.5%)
patients receiving digoxin (according to the judgement of their treating
physician) at the time of screening for BIP participation, was 22.4% compared to
8.3% in the patients who did not receive digoxin. Cardiac mortality was 16.2% in
the digoxin-treated group, compared to 4.9% in the non-treated patients. The
increased risk associated with digoxin remained statistically significant when
patients were stratified according to sex, age groups, functional capacity and
the presence of hypertension, diabetes or angina. The administration of digoxin
to survivors of an acute myocardial infarction in the chronic phase of their
disease, is statistically associated with a 30-50% increase in the risk of
overall and cardiac mortality during long-term follow-up. A propensity of
increased risk of arrhythmias in ischemic coronary patients may explain this
finding.
PMID- 10189001
TI - Automation of follow-up and data analysis of paediatric heart disease in Malta.
AB - Widely available computer programs have been used to set up a database for
patients with congenital heart disease in Malta. This database is used for
clinical follow-up and research, and has been tailored to provide formatted
output of specified results of follow-up as tables and graphs that are
automatically updated with ongoing changes in the dataset. The system is easy to
use, being menu- and icon driven and can be operated with minimal training. It
has resulted in great saving of time not only in clinical practice, but also in
the production of reports and analysis of data, as spreadsheets need only be
created once and are then updated at will. The system also incorporates a patient
summary generator and a on-screen picture library for patient explanation and
teaching purposes.
PMID- 10189002
TI - Syndromes and malformations associated with congenital heart disease in a
population-based study.
AB - Congenital cardiac malformations are frequently associated with non-cardiac
malformations and chromosomal anomalies. Management is therefore influenced by
interventional needs for all of the various anomalies. We have studied the
association of congenital heart disease with extracardiac anomalies in the
relatively closed population of Malta, where echocardiographic screening of all
syndromic/multiply malformed infants is routinely carried out. Malformations were
classified by using the EUROCAT method, for the first time. During 1990-1994, the
birth prevalence of congenital heart disease was 8.8/1000 live births (n = 231).
Of these, 21 (9%) had recognised chromosomal anomalies (0.80/1000 live births;
95% CI: 0.51-1.25), four (2%) had recognised non-chromosomal syndromes and 14
(6%) had other, major, non-cardiac malformations (0.69/1000 live births; 95% CI:
0.42-1.11). The commonest non-cardiac anomalies were musculoskeletal anomalies.
Down syndrome accounted for 95% of all syndromic congenital heart disease, with a
birth prevalence of 0.73/1000 live births (95% CI: 0.45-1.16). Comparison of
these results with earlier studies showed wide disparities between studies, and
this was attributed to differences in methods. such as differing inclusion
criteria for both congenital heart disease and syndromes and malformations. The
commonest lesion found in association with Down syndrome was isolated ventricular
septal defect, not atrioventricular septal defect, and this was attributed to our
screening process which identifies small lesions which would otherwise have been
clinically missed and/or closed spontaneously.
PMID- 10189003
TI - The ergoreflex in patients with chronic stable heart failure.
AB - BACKGROUND: The main symptoms of chronic heart failure are breathlessness and
fatigue on exertion. Abnormalities of skeletal muscle cause early metabolic
distress on exercise, with resultant ergoreceptor stimulation causing increased
ventilation. The aim of this study is to determine the extent of enhanced
ergoreflex activity in chronic heart failure in the leg. METHODS: Ten patients
with chronic stable heart failure (New York Heart Association class II-III) and
nine healthy age-matched controls performed two bouts of ankle dorsiflexion. On
one occasion a cuff was inflated round the thigh to suprasystolic levels for 3
min immediately post-exercise: regional circulatory occlusion. Recovery with
regional circulatory occlusion was compared to recovery without it. RESULTS:
Systolic and diastolic blood pressure and ventilation were higher after 3 min
post-exercise regional circulatory occlusion than after 3 min control recovery in
the patient group (184+/-13.3 vs. 165+/-12.5 mm Hg, P<0.01, 94+/-4.7 vs. 86+/-3.5
mm Hg, P<0.05, 9.8+/-0.7 vs. 7.9+/-0.36 l/min, P<0.01). Systolic and diastolic
blood pressure were higher after post-exercise regional circulatory occlusion
than after control recovery in the control group (149+/-7.8 vs. 138+/-5.7 mm Hg,
P<0.01, 86+/-3.3 vs. 82+/-2.5 mm Hg, P<0.05), but this was not the case for
ventilation (8.1+/-0.62 vs. 8.1+/-0.62 l/min). Ergoreflex activity was greater in
the patient group than in the controls for systolic blood pressure (91 vs. 48%,
P<0.001), diastolic blood pressure (86 vs. 49%, P<0.05) and ventilation (39 vs.
1%, P<0.05). CONCLUSIONS: Ergoreceptor stimulation contributes to an increased
ventilation and blood pressure response to leg exercise in chronic heart failure
patients, perhaps contributing to dyspnoea and exercise limitation. Peripheral
factors such as skeletal muscle abnormalities contribute to the pathogenesis of
symptoms in chronic heart failure.
PMID- 10189004
TI - Higher heart rate variability of smokers after acute myocardial infarction.
AB - Although cigarette smoking is known to be a strong risk factor for the
development of coronary artery disease, several large clinical studies have
demonstrated that current smokers had a favorable prognosis compared to
nonsmokers after myocardial infarction. This study sought to evaluate the effect
of smoking status on heart rate variability after onset of acute myocardial
infarction. We studied 52 patients (34 smokers, 18 nonsmokers) with a first
myocardial infarction within 24 h of onset. We recorded 24-h ambulatory ECG to
calculate very low frequency power (VLF), low frequency power (LF) and high
frequency power (HF) 14 days after onset. Although smokers had a tendency to be
younger than nonsmokers (mean age 57 versus 62, P = 0.0812), clinical
characteristics were not statistically different between smokers and nonsmokers.
After adjustment for age, left ventricular ejection fraction, history of
diabetes, acute revascularization and use of beta-blockers, VLF (P = 0.0183) of
smokers 14 days after onset was significantly higher than for nonsmokers. In
conclusion, although smoking reduces heart rate variability in the general
population, higher heart rate variability was observed in smokers than nonsmokers
after acute myocardial infarction under the condition of smoking cessation.
PMID- 10189005
TI - Potential risk of beta-blockade withdrawal in congestive heart failure due to
abrupt autonomic changes.
AB - Beta-Blockers reduce mortality in patients with congestive heart failure and a
proposed mechanism has been changes of autonomic tone. Heart rate variability is
a non-invasive tool to estimate cardiac autonomic tone. The aim was to study
changes of heart rate variability in patients with congestive heart failure on
placebo, on the beta1-selective antagonist metoprolol or 24 h after metoprolol
withdrawal. Forty-five patients with congestive heart failure were studied with
Holter recordings. Heart rate variability measurements were performed before,
after 6-12 months of treatment with 150 mg metoprolol/placebo, or 24 h after
discontinued metoprolol. After treatment, patients on beta-blockade had a
significantly longer mean RR interval and changes of heart rate variability,
suggesting elevated vagal tone. Patients monitored in the rebound phase of beta
blocker withdrawal had a significant vagal reduction to the level of the placebo
group. There was also a nonsignificant trend towards increased sympathetic tone
(LF/HF over 24 h), compared with the beta-blockade group. Heart rate variability
indicates an elevated vagal tone during treatment with metoprolol but beta
blockade withdrawal shifts the autonomic balance towards lower vagal and higher
sympathetic tone within 24 h. These results could imply a potential risk when
abruptly discontinuing beta-blockade medication in these patients.
PMID- 10189006
TI - Correlation of fasting serum C-peptide and insulin with markers of metabolic
syndrome-X in a homogenous Chinese population with normal glucose tolerance.
AB - We surveyed 1447 men and 1800 women aged 30 years (mean 46.7 years) with normal
glucose tolerance in Kin-Chen, Kinmen. Correlations of fasting serum insulin and
C-peptide with various clinical and biochemical parameters were analyzed by
multiple linear regression analysis. Women had significantly higher levels of
insulin than men (98+/-43 vs. 91+/-43 pM, p<0.0001), yet they also had a more
favorable cardiovascular risk profile. Insulin was positively associated with the
female sex, height, body mass index, waist-to-hip ratio, serum triglyceride,
total cholesterol, uric acid, and fasting plasma glucose, and was negatively
associated with age, smoking, and high-density lipoprotein cholesterol.
Independent correlates for C-peptide were similar to those of insulin, except for
the addition of mean blood pressure and the exclusion of age and total
cholesterol. Significant interaction of sex-body mass index (coefficient =
0.0051, p = 0.0232) was detected for C-peptide only. In conclusion, both fasting
serum insulin and C-peptide are quantitatively associated with cardiovascular
risk factors in this homogeneous Chinese population with normal glucose
tolerance. The female sex is independently associated with higher insulin and C
peptide levels, and the strength of the positive association between the female
sex and C-peptide reduces when the body mass index increases.
PMID- 10189007
TI - Safety of oral propafenone in the conversion of recent onset atrial fibrillation
to sinus rhythm: a prospective parallel placebo-controlled multicentre study.
AB - AIM: Oral propafenone is effective in restoring sinus rhythm however the
proarrhythmic effects are still unknown. The Safety Antiarrhythmic Therapy
Evaluation (SATE) trial was a prospective randomized placebo-controlled
multicentre study which evaluated the safety of acute oral loading dose of
propafenone in patients with recent onset atrial fibrillation. Secondary end
points were to evaluate the effect of digitalis added to propafenone in
ventricular rate control and the efficacy of propafenone alone or added to
digitalis compared with efficacy of digitalis plus quinidine. METHODS AND
RESULTS: 246 patients (126 male; 58+/-11 years) with atrial fibrillation of <48 h
duration were randomly allocated to one of four groups: digitalis 0.75-1 mg i.v.
plus quinidine 1100 mg (D+Q, 70 patients); propafenone 450-600 mg orally (PNF, 66
patients); propafenone 450-600 mg orally plus digitalis 0.750-1 mg i.v. (PNF+D,
70 patients); placebo (Pl, 40 patients). All patients underwent 24-h ECG Holter
monitoring. Safety was assessed by evaluating the appearance of adverse events
classified as mild, moderate and severe. No severe adverse events were reported.
Short lasting asymptomatic atrial flutter episodes with atrio-ventricular
conduction > or =2:1 were observed in 14% of the D+Q group, 21% PNF, 18% PNF+D
and in 8% Pl. One patient in the D+Q group and four in the PNF+D group showed
asymptomatic runs of 3-4 ventricular ectopic beats. Reversible sinus atrial
blocks (<3 s) were detected in two patients of the D+Q group and in two of the
PNF group. In patients with persistent atrial fibrillation the ventricular rate
was similar in the four study groups. At 3 h the high efficacy of propafenone was
confirmed. At the 24th hour no differences were found between active treatment
and placebo arms. CONCLUSION: Propafenone in a single oral loading dose is safe
and promptly effective in patients with recent onset atrial fibrillation.
PMID- 10189008
TI - Diagnostic and surgical trends, and epidemiology of coarctation of the aorta in a
population-based study.
AB - Birth prevalence, and diagnostic and interventional trends for coarctation of the
aorta were analysed in an Island population for patients born between 1925 and
1994. This lesion was diagnosed in 64 live births. A declining trend for age at
diagnosis and age at surgery was present for the entire period (P<0.0001),
predating the introduction of echocardiography, which caused a further decline.
Mode of diagnosis changed from clinically, with or without preoperative catheter
confirmation, prior to the mid-1980s, to almost exclusively by echocardiogram.
Type of intervention was related to era, with patch aortoplasty and end-to-end
resection in the mid 1960s to the mid-1970s changing to subclavian flap
aortoplasty in the late 1970s and early 1980s followed by a return to end-to-end
resection. The perioperative results showed an increase in mortality associated
with a change towards earlier age at surgery. Prior to intervention, all Maltese
patients are reviewed by a consultant cardiologist from a tertiary referral
centre in the United Kingdom, and intervention is undertaken by a consultant
paediatric cardiothoracic surgeon in the same setting. For this reason, these
trends may be extrapolated to larger European countries. The birth prevalence of
coarctation for all patients born between 1980 and 1994 was 0.32/1000 live births
(n = 26), well within the range obtained from a review of previous studies. In
conclusion, in Malta, coarctation of the aorta has been diagnosed and treated
safely, at progressively younger ages, and this has been attributed to improving
medical services over the period under study.
PMID- 10189009
TI - Cyclosporine A modulates baroreceptor function in kidney transplant recipients.
AB - Cyclosporine has been described to increase the sympathetic tone. Alterations in
sympathetic tone may contribute to baroreceptor dysfunction. Therefore, in this
study baroreceptor function in 20 kidney transplant recipients was investigated
under both low and high cyclosporine whole blood concentrations using the
sequence analysis technique. The sympathetic nerve activity was estimated by
calculating the low frequency oscillation of heart rate and blood pressure
following Fast Fourier Transformation (FFT). Besides cyclosporine, azathioprine
and prednisolone no other drugs were used. The increase in cyclosporine whole
blood levels (from 101+/-13.4 ng/ml to 469+/-52 ng/ml) did not change mean
arterial blood pressure significantly (83.7+/-2.5 vs. 82.2+/-2.0 mm Hg).
Baroreflex sensitivity in +PI/+RR (+pulsinterval/+blood pressure) sequences,
however, increased from 11.2+/-0.4 to 13.0+/-0.5 ms/mm Hg, whereas it was reduced
in -PI/-RR (-pulsinterval/-blood pressure) sequences (14.4+/-0.3 to 12.5+/-1.1
ms/mm Hg). The increase in cyclosporine whole blood concentrations was associated
with an increase in low frequency oscillation of heart rate (430+/-12 to 461+/
13) and blood pressure (452+/-9 to 469+/-12), indicating an enhanced sympathetic
tone. Our results provide evidence that cyclosporine A by itself alters
baroreceptor function. An imbalance between the sympathetic and parasympathetic
nervous system due to an enhanced sympathetic tone may explain the reduction in
PI/-RR and the increase in +PI/+RR sequence baroreflex sensitivity.
PMID- 10189010
TI - Clinical value of parameters derived by the application of the proximal
isovelocity surface area method in the assessment of mitral regurgitation.
AB - To determine the clinical value of several parameters derived by application of
the proximal isovelocity surface area method in the assessment of mitral
regurgitation (MR), 28 consecutive patients with angiographic diagnosis of MR
underwent color Doppler echocardiography within 48 h of cardiac catheterization.
Aliasing velocities (V(N)) were baseline-shifted to 25 cm/s and the maximal
radius (R) was measured from the first aliasing boundary to the tips of the
mitral valve. By continuity, the regurgitant orifice area (ROA) and regurgitant
stroke volume (RSV(PISA)) were obtained. We have related them to the angiographic
grade, and with determination of the regurgitant stroke volume (RSV(DE)) and the
regurgitant fraction (RF), we calculated the volume of the transmitral flow
according to Fisher's method. RESULTS: RSV(DE) correlated well with RSV(PISA) (r
= 0.98). A clear relation existed between the isovelocity radius and the RSV(DE)
and RF (r = 0.95 and 0.88, respectively). A radius of 8 mm or more was identified
well with an RSV(DE) of 40 cm3 or more (sensitivity: 100%, specificity: 95%) and
an RF of 35% or more (sensitivity: 88%, specificity: 94%). The ROA was closely
related to the RSV(DE) and RF, with r = 0.92 and 0.88, respectively. An ROA of 20
mm2 or more identified well patients with RSV(DE) values of 40 cm3 or more and RF
values of 35% or more. The radius, RSV(PISA) and ROA were closely related to the
angiographic grade of MR (r = 0.91, 0.83 and 0.92, respectively). A radius of 7
mm or more identified patients with grade III or IV of regurgitation
(sensitivity: 82%, specificity: 94%), while an ROA of 15 mm2 or more
discriminated well significant regurgitation (sensitivity: 91%, specificity:
94%). CONCLUSIONS: Parameters derived by application of the proximal isovelocity
surface area method provide quantitative information that can be helpful in
predicting the severity of mitral regurgitation noninvasively.
PMID- 10189011
TI - Immediate and delayed effects of successful percutaneous transvenous mitral
commissurotomy on global right ventricular function in patients with isolated
mitral stenosis.
AB - Global right ventricular function of the pressure-overloaded right ventricle in
patients with mitral stenosis and pulmonary hypertension after successful
percutaneous transvenous mitral commissurotomy (PTMC) has not been well-defined.
With the use of a recently developed Doppler method for estimating right
ventricular function in human beings, we studied 25 consecutive patients with
isolated rheumatic mitral stenosis before, immediately after (mean, 40+/-12 h)
and at a mean follow-up of 11.5 months after PTMC. Immediately after percutaneous
mitral commissurotomy, there was a significant increase in mitral valve area (P =
0.000017) along with a decrease in mean pulmonary pressure (P = 0.001). The index
was not affected immediately after successful PTMC (0.70+/-0.25 vs., 0.58+/-0.18;
P = 0.06); however, at follow-up of about one year, the index showed a
significant decrease (0.697+/-0.28 vs. 0.380+/-0.13; P = 0.0008, n = 24). The
change in the index was characterised by a significant prolongation of the right
ventricular ejection time, with a decrease in the isovolumic intervals. The
Doppler index of combined right ventricular function was significantly correlated
to the mean pulmonary artery pressure (r = 0.695, P<0.001) and systolic pulmonary
artery pressure (r = 0.60, P = 0.007) before PTMC and also immediately after the
procedure; however, at follow-up, the index had no correlation with the Doppler
estimated pulmonary artery systolic pressure (r = 0.07). Despite a larger mitral
valve area following PTMC, right ventricular isovolumic indices remain abnormal
on mid-term follow-up, although global function tends to normalise in two-thirds
of the patients.
PMID- 10189012
TI - Magnetic resonance imaging of ductus arteriosus Botalli apertus in adulthood.
AB - Ductus arteriosus Botalli apertus is a congenital cardiovascular malformation
usually diagnosed in childhood by echocardiography and/or cardiac
catheterization. Reports about magnetic resonance imaging of ductus arteriosus
Botalli apertus are rare. We report about three adult female patients and one
adult male patient in whom magnetic resonance imaging was able to demonstrate the
pathology. In all four patients quantitative data about right ventricular
function were calculated. Pulmonary hypertension with Eisenmenger syndrome
detected by cardiac catheterization had developed in three of the four patients
excluding operative closure of the ductus. The patient in whom pulmonary
hypertension had not developed underwent successful operative closure of the
ductus. Magnetic resonance imaging is a non-invasive tool that can be used for
diagnosis of ductus arteriosus Botalli apertus and it allows to quantify right
ventricular function. Magnetic resonance imaging can be used repetitively in
patients with Eisenmenger syndrome which may be helpful for better timing of
combined heart-lung transplantation as ultimate therapeutic strategy because
deterioration of right ventricular function can be monitored.
PMID- 10189013
TI - Regression of ductus arteriosus aneurysm in a neonate demonstrated by three
dimensional computed tomography.
AB - We present a case of ductus arteriosus aneurysm in a neonate in whom the
diagnosis was made by echocardiography, three-dimensional surface rendering
computed tomography (CT) and was subsequently confirmed by angiography.
Regression of aneurysm after indomethacin treatment was clearly demonstrated in a
follow-up CT scan. To our knowledge, this is the first report of ductus
arteriosus aneurysm and its regression detected by 3D surface rendering CT.
PMID- 10189014
TI - Subdivided left atrium mimicking a cardiac tumor.
AB - We describe a 25-year-old man with a subdivided left atrium. The lesion was
misdiagnosed preoperatively as a cardiac tumor because echocardiographic and
magnetic resonance imaging revealed a solid mass arising from the posterior wall
of the left atrium. Cardiac surgery revealed a small accessory chamber draining
the two left pulmonary veins. No membranous structure was evident between the
chamber and the left atrium. The solid mass identified noninvasively was a
hypertrophic muscle which formed a wall of the accessory chamber.
PMID- 10189016
TI - Buerger's disease.
PMID- 10189015
TI - Aorto--bronchial fistula resulting from an accidental fall one year earlier.
AB - A 75-year-old woman presented with massive haemoptysis 12 months after tripping
over her shopping trolley. CT scanning and transoesophageal echocardiography
demonstrated a traumatic false aneurysm which was confirmed at surgery to be
partially ruptured. Aortobronchial fistula is an unusual cause of massive
haemoptysis. It should be considered particularly in patients known to have
abnormalities of the thoracic aorta.
PMID- 10189017
TI - Pericarditis associated with longstanding mesalazine administration in a patient.
AB - An adult male patient was admitted for a pericardial effusion occurring during a
longstanding mesalazine treatment for Crohn's disease. The relation between the
drug's administration, symptoms and ECG changes suggests that the pericardial
injury was caused by mesalazine. Also, the rapid resolution of clinical signs and
ECG changes following the drug withdrawal were in agreement with this hypothesis.
Eight months later, the patient remains well and symptom-free, and ECG and
echocardiographic control were normal.
PMID- 10189018
TI - Three dimensional volume measurement of the cervix during pregnancy compared to
conventional 2D-sonography.
AB - OBJECTIVE: To compare the three dimensional (3D) volume assessment of the cervix
with the conventional two-dimensional cervical length measurement in a low and a
high risk group for cervical incompetence. METHODS: In an observational study, we
investigated a group A of low risk pregnancies (no preterm contractions, no
vaginal bleeding or vaginal infections and no history of preterm delivery) and a
group B of high risk pregnancies (preterm contractions or PROM). All patients
underwent a transvaginal ultrasound investigation with a 7.5 MHz probe using a
three-dimensional ultrasound system (Combison 530, Kretztechnik, Austria). After
measuring the cervical length, the internal os and the funneling with the B-mode,
3D-volume was recorded twice by the same investigator using the same machine.
Since 2D-length measurement of the cervix has been established to be predictive
for spontaneous preterm delivery, we wanted to test whether 3D-volume assessment
has a better discriminative power to differentiate a high-risk from a low-risk
group. Therefore the 2D and 3D measurements (mm, resp. cm3) were compared between
patient groups A and B using the two tailed Student t-test and Fisher's Exact
test. RESULTS: In 2D cervical length measurement the mean cervical length in
group A was significantly longer than in group B: 41.1 +/- 8.61 mm and 27.77 +/-
10.42 mm, P = 0.00000017. In 3D-sonography the mean cervical volume was larger in
group A, but the difference compared to group B was not significant: 47.71 +/-
18.38 mm and 39.90 +/- 12.57 mm, P = 0.07. CONCLUSION: Contrary to our hypothesis
cervical length measurement therefore was superior to cervical volume measurement
assessed by 3D ultrasound for identifying women with increased risk of
spontaneous preterm delivery. This may be due to the larger distribution of
measurement values in the 3D group.
PMID- 10189019
TI - Impaired antioxidant activity in women with pre-eclampsia.
AB - OBJECTIVE: To investigate antioxidant activity of sera and the plasma blood
levels of two potent antioxidant in women with pre-eclampsia and normotensive
pregnancies. STUDY DESIGN: The antioxidant activity of sera and the blood levels
of ascorbic acid and alpha-tocopherol were assayed in women with normal
pregnancies (n = 33), mild pre-eclampsia (n = 8), and severe pre-eclampsia (n =
16) between 20 and 40 weeks' gestation. Ascorbic acid and alpha-tocopherol
concentrations were analyzed by high-performance liquid chromatography.
Antioxidant activity of sera was measured as the percent inhibition of
spontaneous autoxidation of a standard brain homogenate. RESULTS: Plasma levels
of ascorbic acid in women with mild and severe pre-eclampsia were significantly
lower than normal pregnancies (P < 0.05). Sera alpha-tocopherol levels were
significantly decreased only in severe pre-eclampsia (P < 0.05). Sera antioxidant
activity were significantly decreased in mild (73%) and severe (51%) pre
eclampsia compared with normal (86%) pregnancies (P = 0.02, P = 0.000,
respectively). CONCLUSIONS: In women with pre-eclampsia, sera antioxidant
activity and antioxidant level of plasma are decreased when compared with
normotensive pregnancies. Impaired antioxidant activity and the reduction of
antioxidant levels which increase the level of lipid peroxidation products may
cause peroxidative damage of vascular endothelium and result in clinical symptoms
of pre-eclampsia.
PMID- 10189020
TI - Biophysical profile score in late pregnancy and timing of delivery.
AB - OBJECTIVE: To determine if the Biophysical Profile Score (BPS) as a screening
procedure on patients without antenatal care (unbooked patients), seen in late
pregnancy, is of value in providing an insight into the mode of delivery and
fetal outcome. DESIGN: Prospective case study of pregnant mothers, data
collection and analysis over 2 years at Abha Maternity Hospital, Saudi Arabia.
SUBJECTS: Unbooked patients with abnormal BPS (Group I), and patients with normal
BPS (Group II) used as control subjects, delivered in the hospital from January
1996 through December 1997. RESULTS: The number of normal deliveries was
significantly higher (P < 0.01) in the control group than in the study group
patients. Cesarean section rate was significantly higher in the study group than
in the control group (P < 0.01, OR = 4.48). There was a significant increase in
the number of asphyxiated and meconium aspirated babies in the study group than
in the control group. Neonates that needed mechanical ventilation were
significantly higher in the study group than in the control group (P < 0.01, OR =
10.38). CONCLUSION: These findings suggest that abnormal BPS is invaluable in
effecting delivery, particularly in women without antenatal care, who present in
late pregnancy to an obstetric unit. Patients with abnormal BPS are four times
more likely to be delivered by cesarean section than those with normal BPS.
PMID- 10189021
TI - Mathematical relationships between uterine contractions, cervical dilatation,
descent and rotation in spontaneous vertex deliveries.
AB - OBJECTIVE: To determine the mathematical relationships between the strength and
duration of the uterine contractions, the descent and rotation of the fetal head
and the degree of cervical dilatation in 50 multiparous women with spontaneous
vaginal deliveries using a simple device applied to the fetal vertex. METHOD: A
simple device for monitoring the progress of labor was applied to the fetal
vertex. The device allows the continuous monitoring of descent and rotation of
the fetal head. The amount of descent and the degree of rotation were also
determined by repeated vaginal examinations as well as the degree of cervical
dilatation. The frequency of uterine contractions was also recorded on a
partogram. RESULT: A good correlation was found between the amount of descent of
the fetal vertex (r = 0.975) and between the degree of rotation of the fetal head
(0.83) determined by both methods. Multiple regression analysis was then
performed and the degree of cervical dilatation in cm at any given time during
the first stage of labor was found to be equal to 2.859 + 0.583 fetal head
station in (cm) + 0.1983 internal rotation in degrees -0.0493 (station x internal
rotation) + 0.1599 station2 + 0.3622 uterine contractions per 10 min. A nomogram
was constructed allowing the calculation of cervical dilatation for a given
station of the head, degree of rotation and frequency of uterine contractions.
CONCLUSION: There is a defined mathematical relationship between the degree of
descent and rotation of the fetal head, the degree of cervical dilatation and the
frequency of uterine contractions in multiparous women with vertex presentation.
The first three variables can be continuously determined by using the described
device. Incorporation of the device into a reusable fetal scalp electrode allows
the dual mechanical and electronic monitoring during labor with minimal vaginal
examinations.
PMID- 10189022
TI - Management of diabetic pregnant patients in a tertiary center in the developing
world.
AB - OBJECTIVES: To audit our insulin regimen in our antenatal diabetics. METHODS: 170
pregnant diabetic patients were retrospectively analyzed. RESULTS: The perinatal
mortality rate was 37/1000, vs. a perinatal mortality rate of 30/1000 in our
setting. Cesarean section rate was 49%. Strict blood-glucose control reduced the
incidence of macrosomia and polyhydramnios. Routine amniocentesis for fetal-lung
maturity was not practiced. CONCLUSION: Satisfactory results in pregnant diabetic
patients are achievable with an established insulin regimen in a developing
country.
PMID- 10189023
TI - Vulvar vestibulitis treated by modified vestibulectomy.
AB - OBJECTIVE: A prospective study to evaluate the success of a modified
vestibulectomy in treating vulvar vestibulitis. METHODS: Fifty seven consecutive
women with vulvar vestibulitis and suitable for surgery based on the criteria:
superficial dyspareunia, erythematous vestibular region, positive Q-tip test,
symptoms reduced with local anesthetic cream. A modified vestibulectomy with or
without a modified Fentons procedure was performed. Response was based on return
to normal coitus, 3 months after surgery. RESULTS: Most women suffered from
chronic conditions (median duration of symptoms = 18 months). The median age was
28 years (range 18-53). Any infections were treated prior to surgery. All but 4
(7%) had histological abnormalities, mainly non-specific inflammation. In 18% of
women who had cervical cytology some abnormality was detected. Mean follow-up
time was 12 months (range 2-42). Three women were not evaluable. Complete
response to surgery was achieved in 33 (61.1%) of the women, partial response was
achieved in 15 (27.8%). Six (11.1%) had persistent symptoms, four of whom has
psychosexual problems. CONCLUSION: Presently, surgery remains the most successful
intervention for vulvar vestibulitis. Modified surgery which is less destructive
seems to afford acceptable results. The completion of randomized studies are
needed to recognise the optimum surgical procedure.
PMID- 10189024
TI - The Vecchietti procedure for surgical treatment of vaginal agenesis: comparison
of laparoscopy and laparotomy.
AB - OBJECTIVE: Our goal was to describe the outcomes of women with vaginal agenesis
who had surgical creation of a neovagina using the Vecchietti technique over a 20
year period. We also sought to determine whether the laparoscopic approach would
result in similar outcomes as laparotomy. METHOD: Retrospective analysis of 76
women with vaginal agenesis treated at the University of Verona Hospital between
1976 and 1996 with the Vecchietti procedure. Operative and postoperative records
were reviewed, and sexual histories were obtained. Data were analyzed based on
surgical approach and postoperative sexual satisfaction. Continuous data were
analyzed with student's t-test, and categoric data were analyzed using Fisher's
exact test. RESULT: Those who underwent the Vecchietti procedure with a
laparoscopic approach (N = 7) had similar complication rates (0% vs. 13.0%, P =
0.59) and postoperative neovaginal depth (74.9 mm vs. 73.7 mm, P = 0.93) as those
with laparotomy (N = 69). Similar proportions of women reported inadequate
vaginal lubrication (28.6% vs. 17.4%, P = 0.61) and sexual satisfaction (100% vs.
78.3%) in the laparoscopy and laparotomy groups as well. Operative complications,
neovaginal depth, or degree of lubrication were not good predictors of sexual
satisfaction. CONCLUSION: Outcomes in those women who underwent the Vecchietti
technique via the laparoscopic approach are comparable to those who underwent
laparotomy.
PMID- 10189025
TI - Recurrence of gynecologic malignancy at the vaginal vault after hysterectomy.
AB - OBJECTIVE: Vaginal vault recurrences of genital tract malignancy are not
uncommon, and may be the first sign of recurrent disease. This paper reviews the
experience at Columbia Presbyterian Medical Center. METHODS: The tumor lists from
1993 to 1996 of the Division of Ob/Gyn Pathology at Columbia Presbyterian Medical
Center were reviewed, and correlated with retrospective chart review. RESULTS: Of
36 cases, 13 were from uterine primaries, seven were cervical in origin, eight
were ovarian primaries, and in eight cases, the exact primary was not known at
the time of biopsy. For the cases where the primary diagnosis and disease free
interval were known, the time interval from hysterectomy to vault recurrence
ranged from 1.5 months to 84 months, with a mean of 25.6 months. CONCLUSION:
Vaginal vault recurrences are often the site of recurrent female genital tract
malignancies. Patients treated for gynecological cancer must have regular pelvic
examinations including cytologic examination as part of their oncologic
surveillance.
PMID- 10189026
TI - Biochemical markers of bone turnover during hormone replacement therapy.
AB - OBJECTIVE: To assess the clinical usefulness of bone turnover markers, including
serum osteocalcin (OC), urinary pyridinoline (Pyr) and deoxypyridinoline (D-Pyr),
in monitoring and predicting bone response to hormone replacement therapy (HRT).
METHOD: The relationships between baseline levels or changes in markers and
change in lumbar bone mineral density were examined in 21 surgically-induced
postmenopausal women. RESULTS: Levels of OC, Pyr and D-Pyr in the estrogen
effective group (responders) significantly decreased during HRT and baseline
levels of Pyr and D-Pyr in responders were significantly higher than those in
premenopausal women. CONCLUSION: Bone turnover markers were useful in monitoring
the bone effect of HRT and baseline levels of markers reflect subsequent bone
response to HRT.
PMID- 10189027
TI - Quality development in perinatal care -- the OBSQID project. OBStetrical Quality
Indicators and Data.
AB - This special communication describes the objectives and strategies of the
OBStetrical Quality Indicators and Data collection (OBSQID) project, a pan
European network of researchers, healthcare providers, and professional
institutions and associations using agreed key quality indicators and served by a
common database. OBSQID is based on the general concept of continuous assessment,
management and development of quality of care and is geared to perinatal
medicine. It allows contributors to measure, on an on-going basis, the outcomes
of care they provide against those of other facilities within their own region or
country as well as in Europe. It identifies 'best practices' and allows for the
exchange and transfer of knowledge and expertise through 'twinning' or
collaborative partnerships. It also assists in setting general quality standards
as well as specific guidelines aimed at ensuring all patients high quality, cost
effective care.
PMID- 10189028
TI - Endometriosis in the presacral nerve.
AB - OBJECTIVE: The authors report a case of extremely aggressive endometriosis
involving a 32-year-old woman. METHODS: Different types of medication were used
and various surgical procedures applied in order to reduce the clinical signs and
symptoms. Among the surgical procedures employed was presacral neurectomy when
endometriosis was identified in the presacral nerve. RESULTS: Receptor
determination in the surgical piece was negative. CONCLUSIONS: The etiopathogenic
and therapeutic aspects of this process are discussed.
PMID- 10189030
TI - Transvaginal ultrasonography in antepartum bleeding.
PMID- 10189029
TI - Multiple hepatocellular adenomas in a patient with a history of oral
contraception.
AB - We report a previously undescribed association between multiple hepatocellular
adenomas and the use of oral contraceptives in a 29-year-old woman. She underwent
trisegmentectomy, with 90% of the liver resected. Based on the rather large size
of some of the adenomas at the time of diagnosis, most likely, the lesions were
already present years before they were discovered. The liver was fully
regenerated 6 months after surgery. Four years later, multiple adenomas recurred.
During work-up for a liver transplant, she was found to have cryptococcal
meningitis and pneumohydrocephalus which caused her demise.
PMID- 10189031
TI - Nucleated red blood cells in fetuses delivered for early onset severe pre
eclampsia.
PMID- 10189032
TI - Unsuspected chronic ectopic pregnancy in a patient with chronic pelvic pain.
PMID- 10189033
TI - Metastatic hepatocellular carcinoma of the ovary.
PMID- 10189034
TI - Genital tuberculosis and infertility.
PMID- 10189035
TI - ACOG educational bulletin. Adolescent victims of sexual assault. Number 252,
October 1998. American College of Obstetricians and Gynecologists.
AB - Acquaintance rape and date rape are widespread problems among adolescents.
Clinicians are faced with the challenging responsibility of identifying victims
and providing effective interventional and preventive counseling. Recognizing the
behavioral signals exhibited by victims and understanding adolescents' attitudes
toward violence can help the health care provider to screen patients for current
or past assaults. All adolescents need to be empowered with preventive strategies
to avoid future violence in their relationships. Obstetrician-gynecologists must
work with other health care and legal professionals to develop approaches to help
adolescents. The prevalence of adolescent victimization warrants routine
screening and effective counseling strategies by all obstetrician-gynecologists.
PMID- 10189036
TI - ACOG committee opinion. Monitoring during induction of labor with dinoprostone.
Number 209, October 1998. Committee on Obstetric Practice. American College of
Obstetricians and Gynecologists.
PMID- 10189037
TI - ACOG practice bulletin. Vaginal birth after previous cesarean delivery. Number 2,
October 1998. Clinical management guidelines for obstetrician-gynecologists.
American College of Obstetricians and Gynecologists.
AB - A trial of labor after previous cesarean delivery has been accepted as a way to
lower the overall cesarean delivery rate. In 1995, 27.5% of women who had a
previous cesarean delivery attempted vaginal birth; some clinicians believe that
an even higher percentage is possible. Although there is a strong consensus that
trial of labor is appropriate for most women who have had a previous low
transverse cesarean delivery, increased experience with vaginal birth after
cesarean delivery (VBAC) indicates there are several potential problems. This
document will review the current risks and benefits of VBAC in various situations
and provide practical management guidelines.
PMID- 10189038
TI - Diet and prostate cancer risk: the embarrassment of riches.
PMID- 10189039
TI - Case-control study of diet and prostate cancer in China.
AB - INTRODUCTION: A higher incidence of prostate cancer is observed in the Western
world than in Asian countries. Although it is relatively rare in China, an
increased incidence has been reported in recent years. Studies in high-risk
populations have suggested that dietary fat may play a role in enhancing the risk
of developing prostate cancer. However, limited epidemiologic study has never
examined the role of diet in low risk populations. METHODS: A case-control study
was conducted in 12 cities in China to evaluate the relationship between dietary
factors and prostate cancer risk. We conducted personal interviews with 133
histopathologically confirmed prostate cancer cases diagnosed between 1989 to
1992 and 265 neighborhood controls of similar age. RESULTS: Cases were more
likely than controls to consume food with high fat and from animal sources (p <
0.01). The daily fat intake and the percentage of energy from fat were
statistically significantly higher among cases than among controls (p < 0.01).
The adjusted odds ratio for total fat between lowest quartiles and highest
quartiles was OR = 3.6 (95 percent C.I. 1.8-7.2); for saturated fat, OR = 2.9 (95
percent C.I. 1.5-5.7); and for unsaturated fat, OR = 3.3 (95 percent C.I. 1.7
6.3). DISCUSSION: The data suggest that dietary fat, both saturated and
unsaturated, are associated with an increased risk for prostate cancer in a low
risk population.
PMID- 10189040
TI - Does high soy milk intake reduce prostate cancer incidence? The Adventist Health
Study (United States)
AB - OBJECTIVES: Recent experimental studies have suggested that isoflavones (such as
genistein and daidzein) found in some soy products may reduce the risk of cancer.
The purpose of this study was to evaluate the relationship between soy milk, a
beverage containing isoflavones, and prostate cancer incidence. METHODS: A
prospective study with 225 incident cases of prostate cancer in 12,395 California
Seventh-Day Adventist men who in 1976 stated how often they drank soy milk.
RESULTS: Frequent consumption (more than once a day) of soy milk was associated
with 70 per cent reduction of the risk of prostate cancer (relative risk = 0.3,
95 percent confidence interval 0.1-1.0, p-value for linear trend = 0.03). The
association was upheld when extensive adjustments were performed. CONCLUSIONS:
Our study suggests that men with high consumption of soy milk are at reduced risk
of prostate cancer. Possible associations between soy bean products, isoflavones
and prostate cancer risk should be further investigated.
PMID- 10189041
TI - Dairy products, calcium, phosphorous, vitamin D, and risk of prostate cancer
(Sweden)
AB - OBJECTIVES: Dairy products consistently have been associated with an increased
risk of prostate cancer, yet the mechanism of this relationship remains unknown.
Recent hypotheses propose that 1,25 dihydroxyvitamin D (1,25 D) is protective for
prostate cancer. One study in the United States found that calcium consumption,
which can lower circulating 1,25 D, was associated with higher risk of advanced
prostate cancer, and we sought to address this hypothesis in a distinct
population. METHODS: We analyzed data from a population-based case-control study
of prostate cancer conducted in Orebro, Sweden, with 526 cases and 536 controls.
Using unconditional logistic regression models, we examined the relationship of
dairy products, dietary calcium, phosphorous, and vitamin D with risk of total,
extraprostatic, and metastatic prostate cancer. RESULTS: Calcium intake was an
independent predictor of prostate cancer (relative risk (RR) = 1.91, 95 percent
confidence interval (CI) 1.23-2.97 for intake > or = 1183 vs. < 825 mg/day),
especially for metastatic tumors (RR = 2.64, 95 percent CI 1.24-5.61),
controlling for age, family history of prostate cancer, smoking, and total energy
and phosphorous intakes. High consumption of dairy products was associated with a
50 percent increased risk of prostate cancer. CONCLUSIONS: Our results support
the hypothesis that high calcium intake may increase risk of prostate cancer, and
this relation may underlie previously observed associations between dairy
products and prostate cancer.
PMID- 10189042
TI - Dietary influences of 1,25(OH)2 vitamin D in relation to prostate cancer: a
hypothesis.
AB - Diets high in dairy products and meats are related to higher risk of prostate
cancer incidence or mortality in most ecologic, case-control, and prospective
studies. Recent laboratory and epidemiologic evidence indicates that a high
circulating level of 1,25(OH)2 vitamin D [1,25(OH)2D], the biologically active
form of vitamin D, inhibits prostate carcinogenesis. This paper will examine the
hypothesis that these observations may be linked, specifically that high dairy
and meat consumption increase risk of prostate cancer by lowering 1,25(OH)2D.
High intakes of calcium and phosphorus, largely from dairy products, lower
circulating 1,25(OH)2D level, and sulfur-containing amino acids from animal
protein lower blood pH, which also suppresses 1,25(OH)2D production.
Additionally, high fructose consumption produces a transitory hypophosphatemia,
and may adversely affect calcium and phosphate balance, all of which may
stimulate 1,25(OH)2D production. The evidence that 1,25(OH)2D inhibits prostate
carcinogenesis, and that diets that are high in calcium, phosphorus, and sulfur
containing amino acids from animal protein, as well as low in fructose, tend to
decrease circulating 1,25(OH)2D will be presented. The studies examining these
dietary factors in relation to prostate cancer risk will be reviewed.
PMID- 10189043
TI - Cigarette smoking and breast cancer risk among young women (United States).
AB - OBJECTIVES: To evaluate whether heavy cigarette smoking as a teenager or long
term smoking increases breast cancer risk or, alternatively, whether smoking acts
as an anti-estrogen and reduces risk. METHODS: Data from a multi-center,
population-based, case-control study among women under age 55 were analyzed.
RESULTS: Among women under age 45, there was a modest inverse relation with
current (OR = 0.82, 95% CI = 0.67, 1.01) but not past (OR = 0.99, 95% CI = 0.81,
1.21) smoking. Odds ratios were decreased for current smokers who began at an
early age (0.59 for < or = 15, 95% CI = 0.41, 0.85) or continued for long periods
of time (0.70 for >21 years, 95% CI = 0.52, 0.94). In subgroup analyses, reduced
odds ratios were observed among current smokers who were ever users of oral
contraceptives (0.79, 95% CI = 0.63, 0.98), were in the lowest quartile of adult
body size (0.53, 95% CI = 0.34, 0.81), or never or infrequently drank alcohol
(0.68, 95% CI = 0.47, 0.98). Among women ages 45-54, there was little evidence
for an association with smoking. CONCLUSIONS: These results suggest that breast
cancer risk among women under age 45 may be reduced among current smokers who
began smoking at an early age, or long-term smokers, but require confirmation
from other studies.
PMID- 10189044
TI - Cancer occurrence among European mercury miners.
AB - OBJECTIVES: To study the carcinogenicity of inorganic mercury in humans. METHODS:
We studied the mortality from cancer among 6784 male and 265 female workers of
four mercury mines and mills in Spain, Slovenia, Italy and the Ukraine. Workers
were employed between the beginning of the century and 1990; the follow-up period
lasted from the 1950s to the 1990s. We compared the mortality of the workers with
national reference rates. RESULTS: Among men, there was no overall excess cancer
mortality; an increase was observed in mortality from lung cancer (standardized
mortality ratio [SMR] 1.19, 95 percent confidence interval [CI] 1.03-1.38) and
liver cancer (SMR 1.64, CI 1.18-2.22). The increase in lung cancer risk was
restricted to workers from Slovenia and the Ukraine: no relationship was found
with duration of employment or estimated mercu ry exposure. The increase in liver
cancer risk was present both among miners and millers and was stronger in workers
from Italy and Slovenia: there was a trend with estimated cumulative exposure but
not with duration of employment, and the excess was not present in a parallel
analysis of cancer incidence among workers from Slovenia. No increase was
observed for other types of cancer, including brain and kidney tumours. Among
female workers (Ukraine only), three deaths occurred from ovarian cancer, likely
representing an excess. CONCLUSIONS: Exposure to inorganic mercury in mines and
mills does not seem strongly associated with cancer risk, with the possible
exception of liver cancer; the increase in lung cancer may be explained by co
exposure to crystalline silica and radon.
PMID- 10189045
TI - Self-reported physical and emotional health of women in a low-fat, high
carbohydrate dietary trial (Canada).
AB - OBJECTIVES: While decreased intake of dietary fat may have significant positive
effects on women's health by reducing the risk of cancer and other diseases,
little research has been carried out to determine the potential adverse effects
of dietary fat reduction. This study compares the self-reported physical and
emotional health of 402 low fat intervention and control group participants in
the Canadian Diet and Breast Cancer Prevention Trial. METHODS: Subjects who had
been participating in the dietary intervention trial for at least 2 years
completed 3 mailed questionnaires: two designed to assess physical and emotional
health (MOS 36-Item Short-Form Health Survey (SF-36) and the Women's Health
Questionnaire (WHQ)) and a Health Practices Survey. RESULTS: There were no
significant differences between the study groups on total scores or any of the
subscales/health domains for the SF-36 or the WHQ. In premenopausal women only,
intervention group subjects scored significantly lower on the vasomotor symptoms
scale, indicating less symptom experience. Frequency of visits to physicians and
alternative health practitioners were not significantly different between the
study groups. CONCLUSIONS: The results of this study suggest that participation
in a low-fat, high-carbohydrate dietary intervention did not have any detrimental
effects on participants' self-reported physical health or emotional well-being.
PMID- 10189046
TI - The diagnosis of renal cell cancer in relation to hypertension (United States).
AB - OBJECTIVES: Renal cell cancer has been associated with hypertension or with drugs
to treat it in several studies. We assessed whether the association is explained
by more frequent detection of early renal cell cancer among persons being treated
for hypertension. METHODS: The data were collected in our Case-Control
Surveillance Study, in which patients aged 20 to 69 years were interviewed in
hospitals in Baltimore, Boston, New York, and Philadelphia during 1976-1996. We
compared 134 incident cases of renal cell cancer who were being treated with
drugs for hypertension to 193 untreated cases with respect to the route to
diagnosis and the stage. RESULTS: The relative risk estimate for having been
diagnosed incidentally during a routine examination or workup for another
condition, relative to having been diagnosed because of symptoms of renal cell
cancer, was 1.3 (95 percent confidence interval, 0.7-2.5). The estimate for
diagnosis at stage I or II relative to stage III or IV was 1.2 (0.7-2.1).
CONCLUSION: In Case-Control Surveillance Study data, the relative risk estimate
for renal cancer among users of various classes of antihypertensive drugs is 1.8
or 1.9. The present results suggest that this association can, at most, be
explained only partially by the selective diagnosis of renal cell cancer among
persons being treated for hypertension.
PMID- 10189047
TI - Methyl-deficient diets, methylated ER genes and breast cancer: an hypothesized
association.
AB - Recent molecular studies show that ER-negative breast cancer results from the
lack of ER gene transcription due to the methylation of the CpG island 5' to the
gene. Because CpG island methylation is an early event in carcinogenesis and
because methyl-deficient diets could result in CpG island methylation, it is
relevant to postulate that methyl-deficient diets may be a risk factor for breast
cancer with methylated ER genes (as opposed to the disease with unmethylated ER
genes). This molecular-based etiologic hypothesis may facilitate epidemiological
research on the relationship between breast cancer and diet that has been unclear
until now.
PMID- 10189048
TI - Fried, well-done red meat and risk of lung cancer in women (United States).
AB - OBJECTIVE: Some epidemiological studies suggest that diets high in fat, saturated
fat, or cholesterol are associated with increased risk of lung cancer. Since meat
consumption is correlated with the intake of saturated fat and cholesterol, we
investigated the role of meat intake and cooking practices in relation to lung
cancer risk. METHODS: A population-based case-control study of both non-smoking
and smoking women was conducted in Missouri. A 100-item food frequency
questionnaire (FFQ) with detailed questions on meat consumption was completed by
593 cases and 623 frequency matched controls. We estimated quantity of meat eaten
(grams/day) according to cooking method, and doneness level. Odds ratios (ORs)
and 95% confidence intervals (C.I.s) were calculated using logistic regression.
Multivariate models included age, packyears of smoking, body mass index (BMI,
kg/m2), education, and intake of calories, fat, fruit/fruit juices, and
vegetables. RESULTS: When comparing 90th and 10th percentiles, lung cancer risk
increased for total meat consumption (OR = 1.6, C.I. 1.1-2.4), red meat (OR =
1.8, C.I., 1.2-2.7), well-done red meat (OR = 1.5, C.I.s, 1.1-2.1) and fried red
meat (OR = 1.5, C.I., 1.1-2.0). The odds ratios for 5th vs. 1st quintiles using
the categorical variable for well-done red meat and fried red meat were
essentially the same as reported above; however, the increase in risk was
associated mainly with the 5th quintile. The ORs for a 10-gram increase in
consumption were, 1.04 for total meat, 1.06 for red meat, 1.08 for well done red
meat, and 1.09 for fried red meat. CONCLUSIONS: Consumption of red meat,
especially fried and/or well-done red meat, was associated with increased risk of
lung cancer.
PMID- 10189050
TI - Milk consumption, galactose metabolism and ovarian cancer (Australia).
AB - OBJECTIVES: It has been suggested that increased exposure to galactose, due to
high consumption of dairy foods or reduced galactose metabolism, is associated
with the development of ovarian cancer. We have investigated this in a large case
control study conducted in three Australian states between 1990 and 1993.
METHODS: Approximately 800 histologically-confirmed cases, 800 community controls
and 300 controls recruited through breast-screening clinics completed dietary
questionnaires. Approximately 100 cases and all breast-screening controls also
provided a blood sample for analysis of galactose-1-phosphate-uridyltransferase
(GALT). RESULTS: Ovarian cancer risk was positively associated with increasing
consumption of whole milk and other full-fat dairy foods, but was not associated
with consumption of low-fat dairy foods and was inversely related to consumption
of skimmed milk. There was no association between ovarian cancer and GALT except
among women with abnormally low GALT who had a non-significant 2.5-fold increased
risk of ovarian cancer. CONCLUSIONS: These data do not support the hypothesis
that galactose plays a major role in the development of ovarian cancer and
suggest that reported associations between milk consumption and ovarian cancer
are due to the fat content of milk and not to lactose or galactose. An increased
risk of ovarian cancer in women with abnormally low levels of GALT cannot,
however, be ruled out.
PMID- 10189049
TI - Effects of mass screening for neuroblastoma on incidence, mortality, and survival
rates in Osaka, Japan.
AB - OBJECTIVES: To evaluate the effects of mass screening for neuroblastoma, time
trends of incidence, mortality, and survival of neuroblastoma in Osaka Prefecture
were analyzed. METHODS: Data for this analysis was obtained from the population
based Osaka Cancer Registry. Time trends of incidence and mortality rates were
analyzed by calendar year and by birth cohort. Survival was compared between
before and after the introduction of systematic screening. RESULTS: From 1970-94,
457 cases of neuroblastoma and 182 deaths from neuroblastoma were observed in
Osaka. The annual age-standardized incidence rate per million children increased
from 7.5 in 1970-84 to 20.5 in 1985-94, while the mortality rates did not differ
between these two periods. Analysis by birth cohort showed that the incidence
rate at 0 year of age per 100,000 live births increased from 2.30 in 1970-79
(unscreened) to 19.80 in 1988-89 (screening by high-performance liquid
chromatography, HPLC). The incidence rate in children 1 and 2-4 years of age also
increased according to the introduction of HPLC. The mortality rate in children 1
4 years of age per 100,000 live births slightly decreased from 3.87 in 1970-79 to
3.30 in 1988-89, which was presumed to be derived from the improvement in
survival due to the progress in treatment. CONCLUSIONS: It is strongly suggested
that mass screening for neuroblastoma causes harm because of overdiagnosis, and
it has little effect on decreasing the incidence and the mortality of
neuroblastoma at 1-4 years of age.
PMID- 10189051
TI - Infertility and risk of fatal ovarian cancer in a prospective cohort of US women.
AB - OBJECTIVES: It is difficult to separate the possible role of fertility drugs from
underlying infertility as risk factors for ovarian cancer. The present study
examined the relationship between self-reported infertility and death from
ovarian cancer among married women unlikely to have been exposured to fertility
drugs. METHODS: Women were selected for study from the 676,526 female
participants in Cancer Prevention Study II (CPS-II). After twelve years of follow
up, 797 deaths from ovarian cancer were observed among women with no prior
history of cancer or hysterectomy and 40 years of age or older in 1967 when
ovulatory stimulants were approved in the United States. Cox proportional hazards
modeling was used to compute rate ratios (RRs) and to adjust for other potential
risk factors. RESULTS: Overall, self-reported infertility was not significantly
associated with ovarian cancer mortality (adjusted rate ratio (RR) = 1.1, 95
percent confidence interval (CI) = 0.9-1.3). Ovarian cancer death rates among
nulligravid women with self-reported infertility, however, were 40 percent higher
than for nulligravid women who never tried to become pregnant (RR = 1.4, 95
percent CI = 0.9-2.4). Multigravid women who reported infertility problems were
not at increased risk. CONCLUSIONS: These results suggest that infertility
itself, without concomitant exposure to fertility drugs, may increase risk of
fatal ovarian cancer among nulligravid women.
PMID- 10189052
TI - Pregnancy experience in women who later developed oestrogen-related cancers
(Denmark).
AB - OBJECTIVES: There has been speculation that women with oestrogen-related cancers
have been exposed to high levels of oestrogen in earlier life and therefore also
during their pregnancies prior to the disease. For this reason we examined signs
of reproductive outcome related to oestrogen exposure such as twinning, sex
ratio, birth weight and congenital malformation in women who later were diagnosed
with breast cancer, endometrial or ovarian cancer. METHODS: For 5213 children
born to women who later developed breast cancer, 557 children born to women who
later developed ovarian cancer and 173 children born to mothers with endometrial
cancers we selected as a control four times as many newborns of mothers without
these cancers after matching for mothers' parity, age, date of birth and hospital
attended. All data were extracted from existing nationwide files. Most of the
women's reproductive lives fell within the period of the birth registry from 1973
to 1993. RESULTS: No differences in sex ratio, birth weight or malformation were
found between the newborns to cancer or control mothers in any of the cancer
groups studied. The only significant findings were less than expected births of
twins to mothers who later developed cancer of the ovaries and a higher
proportion of newborns with a birth weight over 4000 g in the cancer corpus
uterus group. CONCLUSION: Although the amount of information is limited for
endometrial and ovarian cancers, we found no strong indication of elevated
oestrogen levels during pregnancy.
PMID- 10189053
TI - Galaninergic signalling and adenylate cyclase.
AB - Galanin is a hyperpolarizing, inhibitory neurotransmitter; its recognition by
seven transmembrane spanning G-protein-coupled receptors leads to a change in
accumulation of cAMP (3'5'-cyclic AMP). Different subtypes of galanin receptor
and G-proteins could be manifested in the mode of inhibitory action of galanin
receptor on the production of cAMP by adenylate cyclase. Galanin analogues,
acting at the adenylate cyclase level as subtype-specific galanin antagonists,
can selectively block the inhibitory effect of endogenous galanin and thereby
have potential as therapeutic agents for several endocrine, neuroendocrine and
neuronal disorders. In this review, the latest results in the field of interplay
between galanin-initiated signal transduction and the cAMP pathway are
summarized.
PMID- 10189054
TI - Alcoholism abolishes the effects of melatonin on growth hormone secretion in
humans.
AB - Chronic alcohol consumption profoundly affects hypothalamic-pituitary function.
The present study was performed in order to establish whether alcoholism modifies
the effects of melatonin (MEL) on the neuroendocrine control of growth hormone
(GH) secretion. For this purpose, the effects of oral administration of 12 mg MEL
or placebo on basal and hypoglycemia-stimulated GH secretion were tested in nine
(40-52-year-old) alcoholic men after 10-31 days of abstinence and in nine age-
and weight-matched normal controls. Hypoglycemia was induced with an intravenous
bolus injection of 0.15 IU/kg body weight of insulin. MEL but not placebo
administration induced a small, but significant increase in basal GH secretion in
the normal controls. In contrast, neither MEL nor placebo treatment significantly
changed the basal serum GH levels in alcoholic men. Both groups showed a similar
hypoglycemic pattern after insulin administration. The GH response to insulin
induced hypoglycemia was significantly lower in alcoholic than in normal
subjects. MEL administration significantly reduced hypoglycemia-induced GH rise
in the normal controls, but not in alcoholic patients. These data show that
alcoholism not only reduces the GH response to insulin-induced hypoglycemia, but
also abolishes MEL actions on basal and hypoglycemia-stimulated GH secretion.
PMID- 10189055
TI - Tachykinin receptors on human monocytes: their involvement in rheumatoid
arthritis.
AB - Three types of tachykinin receptors, namely NK1, NK2 and NK3, are known to
preferentially interact with substance P (SP), neurokinin A (NKA) and neurokinin
B (NKB), respectively. Experimental evidence indicates that SP and NKA modulate
the activity of inflammatory and immune cells, including mononuclear ones. This
study evaluated the effects of mammalian tachykinins and selective tachykinin
agonists and antagonists on human monocytes isolated from healthy donors: SP, NKA
and NKB all evoked a dose-dependent superoxide anion (O2-) production and the NK2
selective agonist [beta-Ala8]-NKA(4-10) induced a full response. The NK3
selective agonist senktide was inactive, while the NK1 selective agonists septide
and [Sar9Met(O2)11]SP displayed some effects. These results indicate that NK2 and
also some NK1 receptors are present in monocytes isolated from healthy donors.
The role of tachykinin receptor activation in rheumatoid arthritis was also
investigated, by measuring O2- production and TNF-alpha mRNA expression in
monocytes isolated from rheumatoid patients. Tachykinins enhanced the expression
of this cytokine in both control and rheumatoid monocytes and NK2 receptor
stimulation was shown to trigger an enhanced respiratory burst in monocytes from
rheumatoid patients. In conclusion, these results indicate that NK2 and NK1
receptors are present on human monocytes, the former being preferentially
involved in rheumatoid arthritis.
PMID- 10189056
TI - Modulation of murine lymphocyte functions by sulfated cholecystokinin
octapeptide.
AB - The effects in vitro of the sulfated octapeptide form of cholecystokinin (CCK-8)
at concentrations ranging from 10(-13) M to 10(-6) M on several functions of
murine lymphocytes were studied, i.e. adherence to substrate, mobility
(spontaneous and directed by chemical gradient or chemotaxis) and spontaneous and
phytohemagglutinin (PHA)-mediated proliferation. Lymphocytes were obtained from
peritoneal suspension as well as from axillary nodes, spleen and thymus of BALB/c
mice. CCK-8, at concentrations from 10(-10) M to 10(-8) M, significantly
inhibited the mobility capacity and the PHA-induced proliferation and increased
the adherence and the spontaneous proliferation of lymphocytes. A dose-response
relationship was observed, with a maximum effect on lymphocyte functions at 10(
10) M. In addition, CCK-8 induced a significant decrease in membrane and cytosol
protein kinase C (PKC) activity in murine lymphocytes, as well as an increase of
intracellular cyclic AMP levels. These results suggest that CCK-8 is a negative
modulator of two important lymphocyte functions in the immune response, i.e.
mobility and mitogen-induced proliferation, and that the PKC activity inhibition
and cAMP increase could be the mechanisms through which CCK inhibits these
lymphocyte activities.
PMID- 10189057
TI - Opioid antagonist naloxone potentiates anxiogenic-like action of cholecystokinin
agonists in elevated plus-maze.
AB - This study investigated the interplay of cholecystokinin (CCK) and endogenous
opioid peptides in the regulation of anxiety. The acute administration of non
selective CCK agonist caerulein (1 and 5 microg/kg) and a selective CCK(B)
receptor agonist BOC-CCK-4 (1, 10 and 50 microg/kg) induced a dose-dependent
anxiogenic-like action in the plus-maze model of anxiety. BOC-CCK-4 displayed a
similar efficacy with caerulein, indicating that the described effect was
mediated via CCK(B) receptor subtype. The opioid antagonist naloxone itself (0.5
mg/kg) did not change the exploratory activity of rats in the plus-maze. However,
the combination of naloxone with the sub-effective doses of caerulein (1
microg/kg) and BOC-CCK-4 (1 microg/kg) induced a significant inhibition of
exploratory behaviour in rats. Accordingly, CCK and endogenous opioid peptides
have an antagonistic role in the exploratory model of anxiety in rats.
PMID- 10189058
TI - Visualization of specific angiotensin II binding sites in the rat limbic system.
AB - The present study examined the distribution of angiotensin-binding cells by using
a fluorescence-coupled angiotensin II in fixed horizontal sections that contained
several limbic structures. In normal female rats, dense staining was found in the
CA3 and CA1 regions and the dentate gyrus of the hippocampus--in the subiculum as
well as in the entorhinal cortex and piriform cortex. Moderate staining was found
in the CA2 region, in the central and medial nuclei of the amygdala. Low-level
staining was obtained in the basolateral and lateral nucleus of the amygdala as
well as in the bed nucleus of the stria terminalis. The co-incubation of
fluorescence-coupled angiotensin II together with angiotensin II in excess and
with saralasin, respectively, suppressed the angiotensin staining in structures
investigated.
PMID- 10189059
TI - An antagonistic monoclonal antibody (B-N6) specific for the human neurotensin
receptor-1.
AB - The neuropeptide neurotensin (NT) interacts with two types of human receptors
(hNTR) termed hNTR-1 and hNTR-2. This study describes a monoclonal antibody (MAb)
specific for hNTR-1, B-N6. This MAb binds specifically to hNTR-1, but not to hNTR
2 transfected CHO cells. B-N6 and NT display a reciprocal competition and react
in a similar way to trypsin, suggesting that the B-N6 epitope is at or close to
the NT binding site on the third extracellular loop. Unlike B-N6, NT induces hNTR
1 internalization. Although neither NT-FITC nor B-N6 binding was detected by flow
cytometry on different human cells, specific mRNA expression for hNTR-1 was
detected in these cells. In CHO cells expressing hNTR-1 and a luciferase gene
coupled to the krox24 reporter, B-N6 and the antagonist SR 48692 inhibited NT
induced intracellular activation of krox24 in a dose-dependent manner. From these
results it is concluded that B-N6 is an antagonistic anti-hNTR-1 MAb.
PMID- 10189060
TI - Galanin induced in sympathetic neurons after axotomy is anterogradely transported
toward regenerating nerve endings.
AB - Peripheral neurons begin to express galanin after axotomy. When neurons in the
superior cervical ganglion were axotomized near (about 2 mm) from the ganglion,
galanin-like immunoreactivity (IR) was maximal within 72 h. Axotomy of neurons in
the middle and inferior cervical ganglion complex (MICG), which could be
performed 2 cm from the ganglia, led to an additional galanin increase 7 and 14
days later. This second increase was not accompanied by changes in galanin mRNA
or the number of galanin-immunostained neurons. Galanin-IR was detectable in a
postganglionic trunk of the MICG 2 days after axotomy. At this time,
immunoreactive fibers were only seen near the lesion site, while later they were
found throughout the trunk. The data suggest that galanin is actively transported
toward the site of nerve crush/transection and that the second increase in
galanin-IR found in the MICG may be due to a saturation of the axonal transport
system.
PMID- 10189061
TI - Reduced mRNA expression of neuropeptide Y in the limbic system of tenascin gene
disrupted mouse brain.
AB - Tenascin-C (TN), an extracellular matrix glycoprotein which reveals both neurite
outgrowth-promoting and growth-inhibiting effects, is generated in the central
nervous system. A previous study reported that TN-gene null mutant mice display
hyperlocomotion and do not easily habituate to unfamiliar environments.
Additionally, these mice display poor appetite, abnormal circadian rhythm and low
pregnancy rate. The present study demonstrated that neuropeptide Y (NPY) mRNA
expression is reduced in the limbic area of the TN gene-deficient mouse brain as
compared to wild-type mice. NPY has been shown to affect emotion, circadian
rhythm and food intake, and the present results suggest that the some behavioural
abnormalities exhibited by TN-mutant mice may be in part due to the low level of
expression of NPY mRNA in the limbic system.
PMID- 10189062
TI - Calcitonin gene-related peptide improves skin flap survival and tissue
inflammation.
AB - The effects of systemic administration of calcitonin gene-related peptide (CGRP)
on survival and inflammation of experimental skin flaps subjected to prolonged
arterial ischemia were studied. An island groin flap was elevated in the rat. The
femoral artery was occluded for 8, 10, 12 or 14 h in four groups of 10 rats. In a
group of 10 sham-operated control animals, the femoral artery was not occluded.
After ischemia, blood flow was restored and flap survival evaluated at day 7.
Following 12 h of ischemia, three flaps (30%) survived, compared with 100%
survival of the control group. In the second part of the study the effects of
CGRP on flap survival were assessed. Eighty flaps were rendered ischemic for 12
h, and received systemic CGRP (10(-7), 10(-8), 10(-9), 10(-10) M) or saline
(control) at the end of the ischemia period. Administration of CGRP (10(-7) M)
significantly increased the number of flaps surviving compared with the control.
The effect of systemic pretreatment of the animals with the CGRP receptor
antagonist CGRP8(-37), followed by CGRP (10(-7) M) treatment was also evaluated
in 10 flaps. Flap survival in this group was 10%. In the third part of the study
the anti-inflammatory effects of CGRP were evaluated. Forty rats were subjected
to arterial ischemia for 12 h, and received systemic CGRP (10(-7) M), or saline
at the end of the period of ischemia. The animals were sacrificed at 24 h and
flap tissue samples were obtained. Myeloperoxidase (MPO) analysis was used as
marker of neutrophil accumulation. CGRP (10(-7) M) significantly reduced the 24 h
MPO accumulation in the flap, compared with saline treatment. A group of animals
was pretreated with CGRP8(-37), followed by CGRP (10(-7) M), and a significant
increase of MPO accumulation was seen, compared with the group treated only with
CGRP. This study suggests that CGRP has a beneficial effect on survival of the
rat ischemic groin flap, and diminishes the inflammatory response to the ischemic
insult.
PMID- 10189063
TI - Modulation of motor functions involving the dopaminergic system by AT1 receptor
antagonist, losartan.
AB - Growing evidence has indicated the existence of a brain renin angiotensin system
and its possible interaction with other putative neurotransmitters and their
receptors. In the present study, the effect of losartan, an AT1 receptor
antagonist, was studied on the motor functions involving the dopaminergic system.
Losartan (5-30 mg/kg) per se decreased locomotor activity without producing motor
toxicity. It partially reversed the apomorphine-induced hyperlocomotion and
stereotypy in mice, and potentiated neuroleptic-induced catalepsy in rats. On
chronic administration (once daily for 21 days) losartan failed to block
apomorphine-induced hyperlocomotion, but the inhibition of stereotypic response
and potentiation of neuroleptic-induced catalepsy remained unaltered. These
observations suggest that losartan inhibited the release of dopamine through AT1
receptor and also suggest the existence of a compensatory mechanism in certain
brain region concerned with dopamine motor function.
PMID- 10189064
TI - Characterization of vasopressin receptor in rat lung.
AB - This study characterized rat lung membrane arginine vasopressin (AVP) receptors
in detail. Specific binding of [3H]AVP to rat lung membranes was dependent upon
time, temperature and membrane protein concentration. Scatchard plot analysis of
equilibrium binding data revealed the existence of a single class of high
affinity binding sites with a Kd of 0.45 nM and a Bmax of 76.6 fmol/mg protein.
Competitive inhibition of [3H]AVP binding showed that neurohypophysial hormones
as well as their synthetic analogues displaced [3H]AVP in a concentration
dependent manner. The order of potencies for the native peptides was: AVP >
lysine vasopressin = arginine vasotocin > oxytocin. Furthermore, potent V1A
receptor antagonists, d(CH2)5Tyr(Me)AVP and dPTyr(Me)AVP, showed high affinity
for lung membranes. In contrast, the V2 receptor agonist, dDAVP, and the specific
oxytocin receptor agonist, [Thr4,Gly7]oxytocin, did not affect AVP binding. These
results suggest that the lung contains the V1A receptor subtype. The lung
membrane AVP receptor characterized in this study may play an important role in
mediating the physiological effects of AVP in the lung.
PMID- 10189065
TI - Augmenting effect of opioids on nitrite production by stimulated murine
macrophages.
AB - The effects of methionine-enkephalin and the selective agonists of mu-, delta-
and kappa-opioid receptor subtypes [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin, [D
Pen(2,5)]enkephalin U-50488 on the production of nitrite by activated peritoneal
murine macrophages were studied. Macrophages were activated with interferon-gamma
plus lipopolysaccharide in the presence or absence of graded concentrations of
opioids. Methionine-enkephalin and mu-; delta- and kappa-agonists combined with
interferon-gamma plus lipopolysaccharide caused an increase in nitrite release
from cultured macrophages. Only 10 mM U-50488 led to a decrease in nitrite
release from interferon-gamma and LPS-stimulated macrophages. This effect was not
produced in a naloxone-sensitive manner. The opioids added to the fresh culture 8
h after the stimulation of macrophages by interferon-gamma plus
lipopolysaccharide--when an inducible form of nitric oxide synthase activity is
presumably expressed--did not alter the rate of nitrite production. This suggests
that the effect of opioids on nitric oxide synthase is produced at the
transcriptional level. The opioid receptor antagonist naloxone reduced the
stimulatory effect of opioids on nitrite production by stimulated macrophages.
Opioids added to the culture of resting macrophages did not change nitrite
release from macrophages which were later induced with interferon-gamma plus
lipopolysaccharide. The results of this study suggest that methionine-enkephalin
can modulate the immune response by controlling, via opioid receptors, the
production of nitric oxide.
PMID- 10189066
TI - Diurnal variations of opioid peptides and synenkephalin in vitro release in the
amygdala of kindled rats.
AB - Pentylenetetrazol (PTZ) kindling was induced in male Wistar rats (250-300 g) by
daily intraperitoneal injections of 35 mg/kg of the convulsant agent.
Immunoreactive (IR)-Met-enkephalin (IR-ME), IR-Leu-enkephalin (IR-LE), IR
heptapeptide (IR-HE), IR-octapeptide (IR-OC) and IR-synenkephalin (IR-Syn) in
vitro release was measured from amygdala slices 24 h after the last stimulus, in
groups of eight rats, every 4 h beginning at 08:00 h. Opioid peptides in vitro
release displayed diurnal variations. IR-ME and IR-Syn showed maximal levels
before the onset of darkness (16:00 h). IR-LE and IR-OC release was enhanced 4 h
later (20:00 h), no changes were detected for IR-HE. These results show that
endogenous opioid system (EOS) release displays diurnal variations. The peak for
the analysed peptides was reached before and during the dark phase. It is
suggested that EOS release enhancement in PTZ-kindled rats, seems to be due to a
compensatory mechanism against the excitation induced by the blockade of the
GABAergic transmission.
PMID- 10189068
TI - Changes of arterial arachidonic acid metabolites in hypertensive patients during
haemodialysis.
AB - It is well known that in haemodialysis patients suffering from oligoanuria,
extracellular hypervolaemia develops and this hypervolaemia is the main reason
for hypertension occurring in some of the patients. The absence of vasorelaxation
during hypervolaemia may be secondary to an increased activity of vasoconstrictor
systems and/or a decreased formation of vasodilator agents like prostaglandin
E2(PGE2) and prostaglandin I2(PGI2). In the present study, arterial PGE2 and
leukotriene C4(LTC4)-like activities and the effect of fluid removal on these
arachidonic acid metabolites during haemodialysis were measured in normotensive
and hypertensive patients. Plasma PGE2 and LTC4-like activities were
significantly different between hypertensive and normotensive patients. PGE2/LTC4
ratio did not change in normotensive patients while it was increased in
hypertensive patients after haemodialysis. These results indicate that
haemodialysis alters the synthesis of arachidonic acid metabolites especially in
hypertensive patients.
PMID- 10189067
TI - High glucose levels modulate eicosanoid production in uterine and placental
tissue from non-insulin-dependent diabetic rats during late pregnancy.
AB - Severe uterine and placental disturbances have been described in diabetes
pathology. The relative severity of these changes appears to correlate with high
glucose levels in the plasma and incubating environment. In order to characterize
changes in eicosanoid production we compared uterine and placental arachidonic
acid conversion from control and non-insulin-dependent diabetes mellitus (NIDDM)
rats on day 21 of pregnancy, into different prostanoids, namely PGE2, PGF22alpha,
TXB2 (indicating the production of TXA2) and 6-keto-PGF1 (indicating the
generation of PGI2). PGE2, PGF2alpha and TXB2 production was higher and 6-keto
PGF1alpha was similar in diabetic compared to control uteri. PLA2 activity was
found diminished in the NIDDM uteri in comparison to control. A role for PLA2
diminution as a protective mechanism to avoid prostaglandin overproduction in
uterine tissue from NIDDM rats is discussed. Placental tissues showed an
increment in TXB2 generation and a decrease in 6-keto PGF1alpha level in diabetic
rats when compared to control animals. Moreover, when control uterine tissue was
incubated in the presence of elevated glucose concentrations (22 mM), similar
generation of 6-keto PGF1alpha and elevated production of PGE2, PGF2alpha and
TXB2 were found when compared to those incubated with glucose 11 mM. Placental
TXB2 production was higher and 6-keto PGF1alpha was lower when control tissues
were incubated in the presence of high glucose concentrations. However, high
glucose was unable to modify uterine or placental prostanoid production in
diabetic rats. We conclude that elevated glucose levels induced an abnormal
prostanoid profile in control uteri and placenta, similar to those observed in
non-insulin-dependent diabetic tissues.
PMID- 10189069
TI - Expression and cellular distribution of cytosolic phospholipase A2 in the rat
ovary.
AB - Cellular expression of cytosolic phospholipase A2 (cPLA2) was investigated in the
rat ovary in different endocrine states. Its mRNA expression was detected by RT
PCR. The immunohistochemistry identified an intense signal for cPLA2 in oocytes.
Granulosa and thecal cells in growing follicles were negative, but turned
positive during the periovulatory period, whereas those in atretic follicles were
highly immunoreactive. The immunoreactive signal was modest in newly formed
corpora lutea (CL) but intensified in functionally and morphologically regressing
CL. These results show a broad but specific distribution of cPLA2 in ovarian cell
types, and suggest its role in ovulation, CL regulation and apoptotic processes.
PMID- 10189070
TI - Involvement of cytosolic phospholipase A2 in the ovulatory process in
gonadotropin-primed immature rats.
AB - The preovulatory LH surge induces a remarkable increase in ovarian prostaglandins
(PGs) which help to mediate the ovulatory process. We investigated whether
cytosolic phospholipase A2 (cPLA2) has a role in this PG production in PMSG/hCG
primed immature rats. The immunoreactive signal for cPLA2 was localized in both
thecal and granulosa layers of mature follicles and became evident in response to
gonadotropins. The PLA2 activity in the whole ovarian cytosol rose slightly after
PMSG stimulation, persisted relatively constant until 24 h after hCG injection
and thereafter increased gradually. Intra-ovarian bursal injection of arachidonyl
trifluoromethyl ketone, a specific inhibitor for cPLA2 ( 1.0-3.0 mg/ovary),
significantly reduced ovarian PGE2 content and the ovulation rate. These results
suggest that cPLA2 exists in periovulatory follicles and functions in PG
production related to the ovulation process.
PMID- 10189071
TI - Effect of IL-1alpha on prostaglandin synthesis of oestrogenized rat uterus is
mediated by nitric oxide.
AB - We examined the possible relationship between cytokines, nitric oxide (NO) and
prostaglandins in the oestrogenized rat uterus. Results indicate that: IL-1alpha
but not IL-2 enhances the synthesis of prostaglandins in oestrogenized rat uteri;
IL-1alpha but not IL-2 induced an augmention of NO production in this tissue; the
effect of IL-1alpha on prostaglandin synthesis is abolished by NMMA, an NO
antagonist; NS-398, a COX-2 inhibitor, prevents the augmention of prostaglandins
produced by IL-1alpha. These results suggest that there is an interaction between
IL-1alpha, NO and prostaglandins and that this interrelationship involves COX-2.
This mechanism might be important during implantation and labor.
PMID- 10189072
TI - Dual influence of aging and vitamin B6 deficiency on delta-6-desaturation of
essential fatty acids in rat liver microsomes.
AB - Delta-6-desaturase (D6D) activity is influenced by many nutritional and non
nutritional factors, among which one of the most important is aging. D6D activity
could be susceptible to the dual influence of aging itself and of nutritional
deficiencies, due to the reduced intake and/or absorption of essential nutrients.
Particularly, vitamin B6 deficiency might be a crucial factor for D6D activity in
aged people. Using 20 month old Sprague-Dawley rats fed a diet with a subnormal
level of vitamin B6, we evaluated D6D activity for linoleic acid (LA) and alpha
linolenic acid (ALA) in liver microsomes, and the fatty acid composition of
microsomal total lipids. We observed a diminished D6D activity for LA and also
for ALA in vitamin B6-deficient animals, being approximately 63% and 81%
respectively of the corresponding activity in control rats. As a consequence,
significant modifications in the relative molar content of microsomal fatty acids
were observed. The content of arachidonic and docosahexaenoic acid, the main
products of the conversion of LA and ALA respectively, decreased, LA content
increased and a decrease in the unsaturation index was observed in liver
microsomes of B6-deficient rats. The foregoing results suggest that the
impairment of D6D activity by vitamin B6 deficiency might be an important factor
in decreasing the synthesis of n-6 and n-3 PUFAs. This may be particularly
important in aging, where D6D activity is already impaired.
PMID- 10189073
TI - Effects of lysine clonixinate on cyclooxygenase I and II in rat lung and stomach
preparations.
AB - Lysine clonixinate (LC) is a drug of antiinflammatory antipyretic and analgesic
activity that produces minor digestive side-effects. This fact induced us to
think that LC is possibly a weak COX-1 inhibitor. In order to investigate our
hypothesis we inhibited cyclooxygenase activity with LC or indomethacin (INDO) in
rat lung and stomach obtained from rats treated with lipopolysacharide (LPS) and
control rats. Rat lung preparations incubated with 14C-arachidonic acid
synthesise mainly PGE2. LC at 2.5 and 4.1 x 10(-5) M does not modify the basal
production of PGE2 (probably COX-1) but at 6.8 x 10(-5) M significantly inhibited
PGE2 production (approximately 48.5% inhibition, P<0.001). On the other hand,
INDO at 10(-6) inhibited the basal production of PGE2 by around 73%. In LPS
treated rats, the production of PGE2 was significantly higher than in the lungs
of control rats, probably due to the induction of COX-2. The addition of LC at
2.7 and 4.1 x 10(-5) M recovered the control values of PGE2 inhibiting, probably
only from COX-2 activity. LC at higher concentrations (6.8 x 10(-5) M) and INDO
10(-6) M inhibited PGE2 formed by COX-2 and also partly by COX-1 activity.
PMID- 10189074
TI - Identifying and developing rugby talent among 10-year-old boys: a practical
model.
AB - The re-entry of South Africa into the international sporting arena and the
resultant need for the identification and development of talent, especially among
formerly deprived groups of people, provided the incentive for this study. Its
aim was to identify the physical, motor and anthropometric variables that will
enable coaches to identify 10-year-old boys, based on their abilities, who could
become successful rugby players. Altogether, 173 ten-year-old boys with no rugby
experience from a cross-section of the population were selected at random and
subjected to 14 physical and motor tests and 14 anthropometric measurements. From
22 schools which participated in the Western Transvaal primary schools under-11
rugby league, the three top teams (n = 45 individuals) were selected and also
tested. The results from these three teams were used as the criteria for rugby
talent among 10-year-old boys. To establish the best predictors of talent, a
stepwise discriminant analysis was conducted: this indicated eight variables
(four motor and four anthropometric) that discriminated maximally between the
talented and the rest of the players of this age. With classification functions
based on these eight variables, 93.8% of all the subjects were classified
correctly, indicating good validity. A canonical analysis, based on the selected
variables, was then conducted on all the under-11 teams that played in the league
in the region (n = 330), and they were ranked according to the scores of the
first canonical variable from the most to the least talented. By comparing these
results with the players who were chosen for the region's primary schools team, a
success rate of 88% in prediction of talent was established. We conclude that
this is a successful and practical method to aid the teacher and the coach in
selecting and developing talent among 10-year-old rugby players in South Africa.
PMID- 10189076
TI - Kinematics and kinetics of the drive off the front foot in cricket batting.
AB - A cinematographic analysis of the drive off the front foot (D) and the forward
defensive stroke (FD) was undertaken to establish the kinematic and kinetic
factors involved in playing these strokes against medium-fast bowling. Fourteen
provincial cricket batsmen were filmed at 100 Hz while batting on a turf pitch
with a specially instrumented bat. Results for the drive off the front foot
revealed that the movement and stroke pattern were generally supportive of the
coaching literature, with the forward defensive stroke forming the basis of the
drive. Certain mechanical differences, although non-significant, were evident to
facilitate the attacking nature of the front foot drive and included a higher
backlift (FD = 0.65 m; D = 0.74 m), later commencement of the stride (FD = 0.64 s
pre-impact; D = 0.58 s pre-impact) and downswing of the bat (FD = 0.38 s pre
impact; D = 0.36 s pre-impact), a shorter front foot stride (FD = 0.72 m; D =
0.68 m) with the front foot placement taking place later (FD = 0.14 s pre-impact;
D = 0.06 s pre-impact), and the back foot dragging further forward at impact (FD
= 0.05 m; D = 0.10 m). The front upper limb moved as a multi-segmental series of
levers, which resulted in the drive showing significantly greater (P< 0.05) peak
bat horizontal velocity at 0.02 s pre-impact (FD = 3.53 +/- 3.44 m s(-1); D =
11.8 +/- 4.61 m x s(-1)) and 0.02 s post-impact (FD = 2.73 +/- 2.88 m x s(-1); D
= 11.3 +/- 4.21 m x s(-1)). The drive showed a significantly greater (P < 0.05)
bat-ball closing horizontal velocity (FD = 24.2 +/- 4.65 m x s(-1); D = 32.3 +/-
5.06 m x s(-1)) and post-impact ball horizontal velocity (FD = 6.85 +/- 5.12 m x
s(-1); D = 19.5 +/- 2.13 m x s(-1)) than for the forward defensive stroke. The
point of bat-ball contact showed nonsignificant differences, but occurred further
behind the front ankle (FD = 0.09 +/- 0.17 m; D = 0.20 +/- 0.13 m), with the bat
more vertical at impact (FD = 62.6 +/- 6.53 degrees ; D = 77.8 +/- 7.05 degrees).
Significant differences (P< 0.01) occurred between the grip forces of the top and
bottom hands for the two strokes, with the principal kinetic finding that the top
hand plays the dominant role during the execution of the drive with the bottom
hand reinforcing it at impact. Similar grip force patterns for the two strokes
occurred during the initial part of the stroke, with the drive recording
significantly greater (P < 0.05) forces at 0.02 s pre-impact (top hand: FD = 129
+/- 41.6 N; D = 199 +/- 40.9 N; bottom hand: FD = 52.2 +/- 16.9 N; D = 91.8 +/-
41.1 N), at impact (top hand: FD = 124 +/- 29.3 N; D = 158 +/- 56.2 N; bottom
hand: FD = 67.1 +/- 21.5 N; D = 86.2 +/- 58.2 N) and 0.02 s post-impact (top
hand: FD = 111 +/- 22.2 N; D = 126 +/- 28.5 N; bottom hand: FD = 65.5 +/- 26.9 N;
D = 82.4 +/- 28.6 N).
PMID- 10189075
TI - The effect of two different 18-week walking programmes on aerobic fitness,
selected blood lipids and factor XIIa.
AB - Forty-nine previously sedentary or low active individuals aged 40-71 years were
allocated to three groups. The long walking group participated in an 18-week
walking programme which consisted of walks lasting 20-40 min; the repetitive
short walking group completed walks of between 10 and 15 min, up to three times a
day, with no less than 120 min between each walk; and the control group
maintained their low level of activity. Both walking programmes began at a
prescribed 60 min x week(-1), which increased steadily up to 200 min x week(-1)
by week 12. During the study, the long walking group walked for an estimated 2514
min (139 min x week(-1)), expending an estimated 67.5 MJ (3.72 MJ x week(-1)) at
an estimated 73% of their age-predicted maximum heart rate and 68% of their
estimated VO2max. The repetitive short walking group walked for an estimated 2476
min (135 min x week(-1)), expending an estimated 58.5 MJ (3.17 MJ x week(-1)) at
an estimated 71% of their age-predicted maximum heart rate and 65% of their
estimated VO2max. The results showed a statistically significant reduction in
heart rate during a standardized step test (pre- vs post-intervention) in both
walking groups, indicating an improvement in aerobic fitness, although the
control group showed a higher average heart rate during the post-intervention
test, indicating reduced fitness. When compared with the male subjects pre
intervention, the females possessed more favourable levels of high-density
lipoprotein (HDL) cholesterol (P< 0.001), apolipoprotein (apo) AI (P < 0.001) and
ratios of total cholesterol:HDL cholesterol (P< 0.02) and low-density lipoprotein
(LDL) cholesterol: HDL cholesterol (P< 0.02). Compared with the controls post
intervention, the walking groups showed no statistically significant changes in
total cholesterol, LDL cholesterol, HDL cholesterol, apo AI, apo AII, apo B, or
the ratios of total cholesterol: HDL cholesterol, LDL cholesterol: HDL
cholesterol, apo AI: apo B or apo AI: apo AII (P > 0.05). Relative to the walking
groups, factor XIIa increased in the control group (P < 0.05). We conclude that,
although both walking programmes appeared to improve aerobic fitness, there was
no evidence of improvements in the blood lipids or associated apolipoproteins of
the walking groups. Further analysis indicated that this apparent lack of change
may have been related to the subjects' relatively good pre-intervention blood
lipid profiles, which restricted the potential for change. The implications of
the observed changes in the coagulation/fibrinolytic factors remain unclear.
PMID- 10189077
TI - Bow-arrow interaction in archery.
AB - A mathematical model of the flight of the arrow during its discharge from a bow
was proposed by Pekalski (1990). His description of the model was incomplete. In
this paper, I give a full description of the model. Furthermore, I propose some
improvements that make his model more consistent with reality. One achievement is
the modelling of contact of the arrow and grip; the pressure button is modelled
as a unilateral elastic support. The acceleration force acting upon the arrow
during the launch is predicted by an advanced mathematical model of bow dynamics.
There is a satisfactory conformity of the simulation and experimental results.
The new model predicts that the arrow leaves the pressure button before it leaves
the string, as reported previously. The ability to model arrow dynamics can be
used to improve the adjustment of the bow-arrow system for optimal performance.
PMID- 10189078
TI - Effects of endurance training on transient oxygen uptake responses in cyclists.
AB - The aim of this study was to determine the alterations in oxygen uptake kinetics
following endurance training in previously trained athletes. Sixteen competitive
cyclists completed 8 weeks of supervised endurance cycle training. Ventilatory
threshold, maximal oxygen uptake (VO2max), oxygen uptake kinetics and simulated
40-km time-trial tests were performed three times over a 4-week period before
training, and then after 4 and 8 weeks of training. The protocol for measuring
oxygen uptake kinetics consisted of three square-wave increments from unloaded
cycling to a power output of 78 W followed by a single increment from 78 to 156
W. No significant differences in any variables were observed over the pre
training period. The ventilatory threshold and VO2max increased, and the time for
40 km decreased (P < 0.05) with training. Shorter VO2 time constants and lower
heart rates were observed during the protocol for measuring oxygen uptake
kinetics (same absolute power output) post-training. These results indicate that
oxygen uptake kinetics may be improved with endurance training in previously
trained athletes.
PMID- 10189079
TI - Exercise intensity and metabolic response in singles tennis.
AB - The aim of this study was to determine exercise intensity and metabolic response
during singles tennis play. Techniques for assessment of exercise intensity were
studied on-court and in the laboratory. The on-court study required eight State
level tennis players to complete a competitive singles tennis match. During the
laboratory study, a separate group of seven male subjects performed an
intermittent and a continuous treadmill run. During tennis play, heart rate (HR)
and relative exercise intensity (72 +/- 1.9% VO2max; estimated from measurement
of heart rate) remained constant (83.4 +/- 0.9% HRmax; mean +/- s(x)) after the
second change of end. The peak value for estimated play intensity (1.25 +/- 0.11
steps x s(-1); from video analysis) occurred after the fourth change of end (P<
0.005). Plasma lactate concentration, measured at rest and at the change of ends,
increased 175% from 2.13 +/- 0.32 mmol x l(-1) at rest to a peak 5.86 +/- 1.33
mmol x l(-1) after the sixth change of end (P < 0.001). A linear regression
model, which included significant terms for %HRmax (P< 0.001), estimated play
intensity (P < 0.001) and subject (P < 0.00), as well as a %HRmax subject
interaction (P < 0.05), accounted for 82% of the variation in plasma lactate
concentration. During intermittent laboratory treadmill running, % VO2peak
estimated from heart rate was 17% higher than the value derived from the measured
VO2 (79.7 +/- 2.2% and 69.0 +/- 2.5% VO2peak respectively; P< 0.001). The
%VO2peak was estimated with reasonable accuracy during continuous treadmill
running (5% error). We conclude that changes in exercise intensity based on
measurements of heart rate and a time-motion analysis of court movement patterns
explain the variation in lactate concentration observed during singles tennis,
and that measuring heart rate during play, in association with preliminary
fitness tests to estimate VO2, will overestimate the aerobic response.
PMID- 10189080
TI - Prediction of elite schoolboy 2000m rowing ergometer performance from metabolic,
anthropometric and strength variables.
AB - In 19 elite schoolboy rowers, the relationships between anthropometric
characteristics, metabolic parameters, strength variables and 2000-m rowing
ergometer performance time were analysed to test the hypothesis that a
combination of these variables would predict performance better than either
individual variables or one category of variables. Anthropometric
characteristics, maximal oxygen uptake (VO2max), accumulated oxygen deficit, net
efficiency, leg strength and 2000-m rowing ergometer time were measured. Body
mass, VO2max and knee extension correlated with 2000-m performance time (r=
0.41, -0.43 and -0.40, respectively; P< 0.05), while net efficiency and
accumulated oxygen deficit did not. Multiple-regression analyses indicated that
the prediction model using anthropometric variables alone best predicts
performance (R = 0.82), followed by the equation comprising body mass, VO2max and
skinfolds (R = 0.80). Although the regression equations increased the predictive
power from that obtained using single variables, the hypothesis that a prediction
model consisting of variables from different physiological categories would
predict performance better than variables from one physiological category was not
supported.
PMID- 10189081
TI - Resilience of anthropometric data assembly strategies to imposed error.
AB - The aim of this study was to examine strategies for selecting a criterion value
during anthropometric data assembly and their resilience to imposed error. Sixty
seven women aged 16-60 years were subjected to three separate series of
measurements, which included six skinfolds and three girths. A random error term
was added to the first of the three series of measurements to produce a pseudo
series containing error, termed the 'erroneous replicated series'. Five
strategies were then used to determine the criterion value of each of the
replication series: the first measurement, the mean of the first two
measurements, the mean of all three measurements, the mean of the closest two
measurements and the median of the three measurements. The technical error
between the criterion values of the true and the flawed replication series for
each of the selection strategies was calculated. We found that, for five of the
skinfolds and all of the girths, the median value provided the smallest technical
error of measurement between the criterion values for the true and erroneous
replication series. We conclude that the strategy of selecting the median of
three measurements is the most resilient to imposed error.
PMID- 10189082
TI - Muscular development motives for exercise participation: the missing variable in
current questionnaire analysis?
AB - Motivation questionnaires that are currently validated do not account for
muscular development motives in exercise populations, and have rarely been used
to examine resistance training populations. Resistance training is a popular and
widely available exercise, so the lack of such motivational information is a
cause for concern. The aim of this study was to assess the need for considering
motives for muscular development. This was achieved by the development of a
simple scale that matched the format and style of the Exercise Motivations
Inventory. The muscular development scale was combined with the 'weight
management' and 'appearance' items of the Exercise Motivations Inventory to form
a 13-item test questionnaire. This was administered to four groups of experienced
exercisers: resistance training males (n = 40), resistance training females (n =
36), males training in a variety of sports (n = 27) and aerobic training females
(n = 40). Factor analysis with varimax rotation revealed a relatively distinct
muscular development factor, but with cross-loading on weight management.
Muscular development was shown to be the most effective discriminator for the
four groups. A multivariate analysis of variance and additional discriminant
analysis revealed a series of significant differences between groups, which
suggests that motive-based differences are more powerful than sex factors in
determining choice of exercise modality. Although the interrelated nature of
muscular development and weight management needs to be recognized and accounted
for, there is a clear need for considering muscular development motives in future
investigations, especially those that intend to examine motives for 'ideal'
physical appearance.
PMID- 10189083
TI - Glaucoma genetics, present and future.
PMID- 10189084
TI - Genetic landmarks through philately--porphyria and its effect on world history.
PMID- 10189085
TI - Evaluation of the facioscapulohumeral muscular dystrophy (FSHD1) phenotype in
correlation to the concurrence of 4q35 and 10q26 fragments.
AB - Probe p13E-11 (locus D4F104S1) detects two highly homologous polymorphic loci on
chromosomes 4q35 and 10q26. Previous reports in the literature have described a
correlation of shortened 4q35-specific fragments and facioscapulohumeral muscular
dystrophy (FSHD1). We have identified 30 FSHDI families (46 patients) carrying
one short 4q35 and one short 10q26 fragment. The clinical data of these patients
were compared with those of 47 families (131 patients) showing a single short
4q35 fragment, in order to evaluate a potentially modifying influence of
shortened 10q26 fragments on the phenotype. According to our results, the
polymorphic locus on 10q26 does not modify the FSHDI phenotype. The normal
population (14%) and our FSHDI population (13%) did not significantly differ in
the overall frequency of short polymorphic 10q26 fragments. The specificity of
the p13E-11/EcoRI-BlnI test for FSHD1 was 100%.
PMID- 10189086
TI - Pattern of central nervous system anomalies in a population with a high rate of
consanguineous marriages.
AB - Nine thousand six hundred and ten births were prospectively studied in the three
major hospitals in Al-Ain, United Arab Emirates (UAE) between October 1995 and
January 1997. Babies suspected of, or diagnosed, as having central nervous system
(CNS) abnormalities were evaluated by a neonatologist, a clinical geneticist and
a pediatric neurologist. Brain computerized tomography/magnetic resonance imaging
(CT/MRI) was performed on all babies suspected of having CNS abnormalities. In
addition, metabolic screening and chromosome analysis were also performed when
indicated. Of the 225 babies with congenital anomalies identified, 31 had CNS
abnormalities (3.2/1000). Syndromic abnormalities of the CNS were present in 13
cases (42%), chromosomal abnormalities in one case (3.2%) and the rest included:
neural tube defect (NTD) in 11 cases (36%), holoprosencephaly in two cases (6.4%)
and hydrocephalus in four cases (12.9%). Detailed analysis of the syndromic types
revealed that out of the 13 cases, 12 were inherited as autosomal recessive (AR)
and in one case the inheritance was undetermined. Consanguinity with high level
of inbreeding was present in 12 cases and the majority of the syndromes
identified were extremely rare. The study indicates that CNS anomalies are fairly
common in the UAE, particularly, the recessive syndromic types. Careful and
detailed analysis of such anomalies is required so that accurate genetic advice
can be given.
PMID- 10189087
TI - Antibody deficiency, growth retardation, spondyloepiphyseal dysplasia and retinal
dystrophy: a novel syndrome.
AB - The clinical and laboratory combination of recurrent infections due to antibody
deficiency, spondyloepiphyseal dysplasia, growth retardation and retinal
dystrophy is novel. Four patients with strikingly similar phenotypes from three
different families of diverse genetic backgrounds are described, suggesting a
similar underlying genotype. Increased awareness of this syndrome will hopefully
lead to the description of a larger number of affected individuals, which
ultimately might be critical for its genetic characterization.
PMID- 10189088
TI - Novel exon skipping mutation in the fibrillin-1 gene: two 'hot spots' for the
neonatal Marfan syndrome.
AB - The Marfan syndrome is an autosomal dominant heritable disorder of connective
tissue that involves principally the skeletal, ocular, and cardiovascular
systems. The most severe end of the phenotypic spectrum, the neonatal Marfan
syndrome (nMFS), is characterized by pronounced atrioventricular valve
dysfunction, and death often occurs within the first year of life due to
congestive heart failure. Mutations in the gene coding for fibrillin-1, FBN1, are
known to cause Marfan syndrome, and have been identified in almost all exons of
FBN1. Here, we describe a novel mutation affecting the invariant + 1 position of
the splice donor site in intron 31, associated with skipping of exon 31, in a
patient with nMFS. Published reports of nMFS are reviewed and a strict definition
for nMFS is suggested. If this definition is used, all nMFS mutations reported to
date lie in one of two hot spots, comprising mainly missense mutations in FBN1
exons 24-27 and mutations causing skipping of exon 31 or 32.
PMID- 10189089
TI - Alternative splicing of exon 37 of FBN1 deletes part of an 'eight-cysteine'
domain resulting in the Marfan syndrome.
AB - A child and his father had the skeletal and cardiovascular manifestations of
Marfan syndrome due to a heterozygous G+5 --> T transversion in intron 37 of the
FBN1 gene. Cultured dermal fibroblasts preferentially used an alternative splice
site in exon 37 that resulted in the loss of the 3' 48 nucleotides of this exon.
The translational reading frame was maintained with deletion of lysine 1568 to
threonine 1582 and splitting of the codons for glycine 1567 and serine 1583 to
yield GCC for alanine. The deletion removed two cysteine residues as well as a
potential N-linked oligosaccharide attachment site from the '8-cysteine' domain
encoded by exons 37 and 38.
PMID- 10189090
TI - Centromere-telomere (12;8p) fusion, telomeric 12q translocation, and i(12p)
trisomy.
AB - The concurrence of a short arm isochromosome and a translocation of the entire
long arm of the same chromosome to a telomere of another chromosome, implying
trisomy for 4p, 5p, 7p, 9p, 10p or 12p, has been described in 13 patients. We
have now used fluorescence in situ hybrization (FISH) to better characterize one
of these rearrangements in which 12q was translocated to 8pter, whereas 12p was
converted into an isochromosome. An alphoid centromere-12 repeat gave a strong
signal on the i( 2p) and a weak but distinct signal at the breakpoint junction of
the der(8), whereas the pantelomeric probe revealed three clear hybridization
sites on the der(8): one at each end and another at the breakpoint junction.
These findings suggest that the prime event was a post-fertilization centric
fission of chromosome 12 leading to the 12q translocation via a real centromere
telomere fusion and the i(12p). Alternatively, the crucial event may have been a
centromere telomere recombination. An interstitial telomere has been documented
by means of FISH at the breakpoint junction of the sole derivative usually
present in 20 constitutional translocations including eight with a jumping
behavior. In addition, six other telomeric translocations defined by banding
methods, including another case of 12q translocation/i(12p), have also been
jumping ones. These telomeric translocations have been de noro events and their
proneness to exhibit a jumping behavior appears to be independent of the involved
chromosomes, size of the translocated segments, and concomitant abnormalities.
PMID- 10189091
TI - Deletion of chromosome 4p detected by FISH in a girl with normal high resolution
karyotype.
PMID- 10189092
TI - Mutations associated with very late-onset metachromatic leukodystrophy.
PMID- 10189093
TI - Preaxial polydactyly in an infant with Down's syndrome.
PMID- 10189094
TI - Gene-gene interactions and neural tube defects.
PMID- 10189095
TI - Novel polyisobutylene/polydimethylsiloxane bicomponent networks: III. Tissue
compatibility.
AB - The tissue biocompatibility of a series of novel rubbery polyisobutylene
(PIB)/polydimethylsiloxane (PDMS) bicomponent networks was investigated by in
vivo implantation into rats. Bicomponent networks of varying composition (PIB
wt%/PDMS wt% = 70/30, 50/50, 35/65) as well as a standard polyethylene control
were implanted intraperitoneally. After eight weeks the implants and surrounding
tissue were removed for histological evaluation. In all scoring categories (i.e.
collagen thickness, fibrous tissue orientation, collagen deposition in muscle
tissue, lymphocyte infiltration, angiogenesis) the PIB/PDMS bicomponent network
implants elicited either less or similar tissue and cellular response than
polyethylene. To determine which implant elicited the least tissue and cellular
response overall, a weighted score including collagen thickness, lymphocyte
infiltration, and angiogenesis was calculated for each implant. According to
these preliminary investigations, PIB/PDMS bicomponent networks are suitable for
implant applications.
PMID- 10189096
TI - Improvement of blood compatibility on cellulose hemodialysis membrane: IV.
Phospholipid polymer bonded to the membrane surface.
AB - To improve the surface blood compatibility on a cellulose hemodialysis membrane,
2-methacryloyloxyethyl phosphorylcholine (MPC) polymers with a phospholipid polar
group were immobilized on the surface through covalent bonding. The MPC polymers
had a carboxylic group, which can react with hydroxyl groups on the cellulose
membrane, and were synthesized by conventional radical polymerization. The
reaction between the MPC polymers and the cellulose membrane was carried out in a
heterogeneous system using a condensation reagent. Surface analysis of the
modified membrane by X-ray photoelectron spectroscopy revealed the immobilization
of the MPC polymer on the surface. The mechanical strength and permeability for a
solute of the membrane did not change even after the modification. The modified
cellulose membrane was blood-compatible, as determined by the prevention of
adhesion, deformation, and aggregation of platelets after contact with platelet
rich plasma. Based on these results, it is concluded that the MPC polymers may be
a useful material for improving the blood compatibility of cellulose hemodialysis
membranes.
PMID- 10189097
TI - Interaction of fibroblasts on polycarbonate membrane surfaces with different
micropore sizes and hydrophilicity.
AB - Surface topography appears to be an important but often neglected factor in
implant performance. In this study, fibroblasts were cultured on a range of
porous polycarbonate (PC) membranes with well defined surface topography (track
etched micropores, 0.2-8.0 microm in diameter) and wettability gradients. The
wettability gradient on the PC membrane surfaces was produced by treating the
surfaces with corona from a knife-type electrode whose power increased gradually
along the sample length. The PC membrane surfaces were characterized by scanning
electron microscopy (SEM) and the water contact angle measurement. Fibroblasts
were cultured on the corona-treated PC membrane surfaces with different micropore
sizes for 1 and 2 days. The cells attached on the membrane surfaces were examined
by SEM and the cell density on the surfaces was estimated by counting the number
of attached cells along the wettability gradient. It was observed that the cells
were adhered and grew more on the hydrophilic positions of the membrane surfaces
than the more hydrophobic ones, regardless of micropore size. It was also
observed that cell adhesion and growth decreased gradually with increasing
micropore size of the membrane surfaces. It seems that the cell adhesion and
growth were progressively inhibited as the membrane surfaces had micropores with
increasing size, probably due to surface discontinuities produced by tract-etched
pores. On the membrane surfaces with smaller micropore sizes, the cells seemed to
override these surface discontinuities.
PMID- 10189098
TI - Langmuir-Blodgett films of antibodies as mediators of endothelial cell adhesion
on polyurethanes.
AB - The effect of endothelial cell adhesion on polyurethanes coated with Langmuir
Blodgett antibody films has been examined. The films were cross-linked with
glutaraldehyde with the aim of providing a densely packed and covalently linked
two-dimensional antibody network on the polyurethane surfaces. Our results
demonstrate that although neither of the two polyurethanes examined were entirely
suited to cellular adhesion, Langmuir-Blodgett antibody films, cross-linked with
small concentrations of glutaraldehyde, are more suitable for endothelial cell
adhesion than surfaces free of antibody.
PMID- 10189099
TI - Diamine-plasma treated and Cu(II)-incorporated poly(hydroxyethylmethacrylate)
microbeads for albumin adsorption.
AB - Poly(2-hydroxyethylmethacrylate) (PHEMA) microbeads prepared by suspension
polymerization were treated with diamine-plasmas (i.e. ethylene-diamine (EDA) and
hexamethylene diamine (HMDA)) in a glow-discharge reactor in which the exposure
time and glow-discharge power were changed between 5 and 30 min and 5 and 20 W,
respectively. The amount of nitrogen deposition increased both with increase in
exposure time and glow-discharge power. The maximum amounts of nitrogen
deposition on the microbeads were 22.3 and 23.4 micromol g(-1) with the EDA- and
HMDA-plasmas. Then, Cu(II) ions were incorporated onto the PHEMA microbeads by
chelating with the nitrogen-carrying functional groups. Different amounts of
Cu(II) ions (2.4-6.8 mg g(-1)) were incorporated on the PHEMA microbeads by
changing the initial concentration of Cu(II) ions. Bovine serum albumin (BSA)
adsorption onto the unmodified PHEMA, diamine-plasma treated PHEMA, and diamine
plasma treated Cu(II)-incorporated PHEMA microbeads was investigated. The non
specific adsorption of BSA on the unmodified microbeads was very low (0.22 mg BSA
g(-1)). Deposition of nitrogen increased the BSA adsorption (9.3 mg g(-1) for EDA
plasma and 12.7 mg g(-1) for HMDA-plasma). Cu(II)-incorporation significantly
increased the BSA adsorption (154 mg g(-1) for EDA-plasma and 178 mg g(-1) for
HMDA-plasma). Further increases in the albumin adsorption capacities of the
polymer microbeads (185 mg g(-1) for EDA-plasma and 208 mg g(-1) for HMDA-plasma)
were observed when human plasma was used. More than 92% of the adsorbed albumin
molecules was desorbed in 1 h in the desorption medium containing 0.5 M NaSCN at
pH 8.0. Repeated adsorption-desorption cycles showed the feasibility of these
plasma-modified polymer microbeads.
PMID- 10189100
TI - Denucleation promotes neovascularization of ePTFE in vivo.
AB - Expanded polytetrafluoroethylene (ePTFE) implants are being increasingly used as
vascular prostheses and other devices. However the tissue response associated
with this and other polymer implants continues to limit any long-term function.
One of the major approaches currently being investigated to improve
biocompatibility involves surface modification of the base polymer. In this
report, we attempted to alter the healing characteristics of ePTFE by
denucleation, a process which removes air trapped within the interstices of the
material. Additionally, adsorption of extracellular proteins on the denucleated
polymer was also tested. After 5 weeks implanted in subcutaneous and epididymal
fat sites of rats, the material was explanted and the healing around the implant
evaluated histologically. We found that in skin implants, denucleation alone
resulted in a substantial reduction in the fibrous capsule which has been
previously reported for untreated ePTFE, and an increase in blood vessel
development around and within the polymer. Absorption of extracellular matrix
proteins prior to implantation resulted in a reduced vascularity of the implants
compared with denucleation-only implants. Implants in fat tissue, regardless of
treatment, showed very little tissue reaction, either in the number of
inflammatory cells, development of a fibrous capsule or neovascularization. These
results suggest that the presence of air nuclei within porous material may
contribute to the inappropriate healing response associated with these polymers.
In addition, they confirm earlier reports that healing around implanted polymers
is tissue-specific.
PMID- 10189101
TI - Apatite formation on/in hydrogel matrices using an alternate soaking process: II.
Effect of swelling ratios of poly(vinyl alcohol) hydrogel matrices on apatite
formation.
AB - In our previous study, we reported a novel method of apatite formation on/in a
three-dimensional hydrogel matrix. Using this method, bone-like apatite could be
formed on/in the hydrogel matrix under normal conditions in vitro. A poly(vinyl
alcohol) (PVA) gel was used as a model matrix. The method consists of two steps:
first, water is transformed in a PVA gel with a CaCl2/Tris-HCl aqueous solution
(pH 7.4) and second, the gel is soaked in a Na2HPO4 aqueous solution. In the
present study, we report a detailed study of the effects of the swelling ratios
of PVA gels on apatite formation. Cross-sectional observations and gravimetric
measurements of PVA gels with various swelling ratios were done. The amount of
apatite formed on/in PVA gels increased almost linearly with an increase in the
reaction cycles. The rates of apatite formation on/in PVA gels largely depended
on the swelling ratios, which were approximately 0.48, 0.61, 1.28, and 1.55 mg
per cycle for swelling ratios of 4.1, 10.4, 16.8, and 30.1, respectively. The
apatite content in PVA-apatite composites that was obtained by this method also
increased with an increase of the reaction cycles. After six reaction cycles, a
PVA gel with a high swelling ratio contains approximately 70 wt% of formed
apatite in the composite. On the other hand, a gel with a low swelling ratio
contains about 15 wt% of formed apatite in the composite. Cross-sectional views
of the PVA gels after each cycle showed that apatite crystals were formed, not
only on the surface of the gel but also within it after fifteen reaction cycles.
The hydrogel-apatite composites that were obtained using an alternative soaking
process will be useful as not only bone substitute materials but also as soft
tissue adhesive materials.
PMID- 10189102
TI - Preparation of DNA-immobilized immunoadsorbent for treatment of systemic lupus
erythematosus.
AB - A new DNA-immobilized immunoadsorbent was prepared to remove the pathogenic anti
DNA antibody from the serum of systemic lupus erythematosus (SLE) patients. A non
woven poly(ethylene terephthalate) (PET) fabric made of 3.5-microm diameter
fibers was used as the support of the immunoadsorbent. A cationic monomer, N,N
dimethylaminoethyl methacrylate (DAM), was graft polymerized onto the PET fiber
surface by UV irradiation or with a chemical initiator. Polyion complexation
between the cationic groups of the graft chains and DNA molecules was employed to
immobilize DNA onto the fiber surface. No DNA leaching was observed when the DNA
immobilized fabrics were placed in 0.9 and 2.0 wt% NaCl solution at 37 degrees C
overnight. In vitro evaluation of this DNA-immobilized immunoadsorbent
demonstrated that this adsorbent could selectively adsorb anti-DNA antibody from
the serum of SLE patients.
PMID- 10189103
TI - Adhesion of macrophages on collagen irradiated with ultraviolet light.
AB - Properties of collagen irradiated with ultraviolet (UV) light were examined using
the techniques of sodium dodecyl sulfate-polyacrylamide gel electrophoresis,
spectroscopic measurements, and cell adhesion assay. Both photopolymerization and
photodegradation of the collagen appeared to occur with UV irradiation because
the aggregation of collagen and disintegration of the triple-helical structure
were observed. The formation of the cross-links between the tyrosine residues in
collagen by photoreaction was presumed. The adhesion of macrophages (Mphis) on a
polystyrene plate was suppressed by coating the plate surface with collagen. Anti
adhesive activity of collagen on Mphi cells decreased with UV irradiation.
However, appreciable anti-adhesive activity remained in the modified collagen
even when collagen was irradiated with UV light for 24 h.
PMID- 10189104
TI - Synthesis of poly(propylene fumarate) by acylation of propylene glycol in the
presence of a proton scavenger.
AB - To synthesize high molecular weight poly(propylene fumarate) (PPF), fumaryl
chloride and propylene glycol were reacted in the presence of potassium
carbonate, which serves as a proton scavenger. Transesterification of the
resulting low molecular weight oligomer led to a polymer with greater molecular
weight than those from previous reaction methods without requiring the use of a
catalyst. According to two-dimensional NMR, the backbone structure of this
polymer was as expected and contained no byproducts formed by acid catalyzed
addition across the fumarate double bond. Kinetic studies of the
transesterification showed that the molecular weight reached a final Mn of 4900
(+/-700) and Mw of 9100 (+/-1300) after 16 h, while the polydispersity index
remained below 1.8 throughout the reaction. Thus the PPF synthesized by the new
method is of higher molecular weight and greater purity than our previously
prepared material.
PMID- 10189105
TI - Synthesis and characterization of self-catalyzed poly(ortho-esters) based on
decanediol and decanediol-lactate.
AB - The synthesis of poly(ortho-esters) (POEs) containing lactic acid dimers in the
polymer backbone for possible use in controlled drug release applications is
described. These autocatalyzed POEs are prepared by the acid catalyzed
condensation of 3,9-diethylidene-2,4,8,10-tetraoxaspiro(5,5)undecane with diols
to produce linear polymers. The diols used were a mixture of decanediol-lactate
and decanediol in various molar ratio to produce polymers with different lactic
acid contents. Polymer structures were confirmed by 13C NMR, 1H NMR, and FT-IR
and physico-chemical properties, such as molecular weights, glass transition
temperatures and viscoelastic behavior, were also determined.
PMID- 10189106
TI - Synthesis of polystyrene nanospheres having lactose-conjugated hydrophilic
polymers on their surfaces and carbohydrate recognition by proteins.
AB - We prepared a poly(vinylamine)-grafted polystyrene nanosphere by the free radical
polymerization of poly(N-vinylacetamide) macromonomer and styrene with AIBN in
ethanol and subsequent acid hydrolysis. We conjugated lactose on the nanosphere
by an amide linkage and found that the lactose was recognized by a galactose
specific lectin RCA120, which was analyzed by enzyme-linked lectin assay (ELLA).
The binding ability of the lectin to lactose on the nanosphere was at least 10(2)
times larger than that to a monomeric lactose. Binding ability was clearly
affected by the lactose density on the nanosphere and showed a maximum value at
the suitable surface density of lactose. We found that the carbohydrate
conjugated nanosphere would be a useful biomaterial for a site specific drug
carrier.
PMID- 10189107
TI - The effect of electro-acupuncture stimulation on the muscle blood flow of the
hindlimb in anesthetized rats.
AB - The effect of electro-acupuncture stimulation (EAS) on blood flow in the muscle
biceps femoris (MBF) and on mean arterial pressure (MAP) was investigated in
anesthetized, artificially ventilated rats. EAS was applied to a hindpaw for 30 s
at intensities of 0.1-10.0 mA and at frequencies of 1-20 Hz, and MBF was measured
by laser Doppler flowmetry. EAS at less than 1.0 mA, which excited group II
fibers maximally and III fibers partially in a saphenous nerve, had no
significant effect on MBF or MAP, although both revealed variable responses. EAS
at 1.5 mA, which additionally excited group III fibers almost maximally and was
subthreshold for group IV fibers, produced a small but significant increase in
MBF and MAP. These responses were further increased at 2.0 mA or more, which was
suprathreshold for group IV fibers. The increased response of MBF at 10.0 mA was
followed by a small decrease in MBF. EAS at 1.5 mA or more also elicited a
decrease in renal blood flow (RBF) and an arterial pressor response. Following
severance of the bilateral splanchnic nerves, EAS at 10.0 mA induced only a
slight increase in MAP and a decrease in MBF. The decrease in MBF was abolished
following further severance of the bilateral lumbar sympathetic trunks (LSTs). In
conclusion, EAS to a hindpaw at a stimulus strength sufficient to excite group
III and IV afferent fibers, particularly group IV afferent fibers, can produce a
reflex decrease in MBF via a reflex activation of muscle sympathetic activity,
although this decrease in MBF is overridden by an increase in MBF caused
passively by a reflex MAP pressor response elicited by a reflex increase, at
least in splanchnic sympathetic activity.
PMID- 10189108
TI - Dilatation of subcutaneous perforating blood vessels associated with capsaicin
induced cutaneous axon reflex: demonstration with subtraction thermography.
AB - The axon reflex induced by intracutaneous application of capsaicin to the forearm
of human subjects and the back of anesthetized rats pretreated with intravenous
injection of Evans blue was investigated using sequential subtraction
thermography. In the human experiment, thermograms showed an immediate and
general temperature decrease after capsaicin injection. Four min after
application, several spotty areas with a temperature increase ('hot spots')
appeared within and outside of the flare caused by capsaicin-induced axon reflex.
A vascular murmur was observed on ultrasonic Doppler flowscopy at the hot spots.
In the rat experiment, two hot spots appeared, one cranial to and one caudal to
the site of injection, within different dermatomes. Hot spots appeared in rats
with the pretreatment of intravenous hexamethonium and surgical removal of the
bilateral lumbar paravertebral sympathetic trunks. Postmortem examination of the
rats revealed that these hot spots coincided with perforating blood vessels. It
was suggested that hot spots in the axon reflex identified by subtraction
thermograms are induced by a passive dilatation of perforating vessels which
supply blood to the flare.
PMID- 10189109
TI - Immunohistochemical distribution of c-Kit-positive cells and nitric oxide
synthase-positive nerves in the guinea-pig small intestine.
AB - Anatomical relationships between c-Kit-positive cells and nitric oxide synthase
positive nerves in the small intestine were examined by double-labeling
immunohistochemistry. Cryosections and whole mount preparations of the guinea-pig
small intestine were double-immunolabeled using anti-c-Kit and neuronal nitric
oxide synthase antibodies, and were observed using confocal laser scanning
microscopy. The c-Kit-like immunoreactivity constituted dense reticular networks
in the deep muscular plexus and myenteric plexus of the intestinal wall. The
nitric oxide synthase-like immunoreactivity occurred in the circular muscle
layer, most densely at the deep muscular plexus, as well as within the ganglion
strands or connecting strands of the myenteric plexus. Close association between
c-Kit-like immunoreactivity and nitric oxide synthase-like immunoreactivity was
evident in the deep muscular plexus. Specimens immunolabeled with the anti-nitric
oxide synthase antibody were further examined under transmission electron
microscopy. Axon profiles with nitric oxide synthase-like immunoreactivity lay
closely adjacent to the interstitial cells in the deep muscular plexus as well as
to smooth muscle cells of the circular muscle layer, whereas there was a
considerable distance (> 500 nm) between interstitial cells and axon profiles
with nitric oxide synthase-like immunoreactivity in the myenteric plexus. These
results suggest that the interstitial cells in the deep muscular plexus serve as
mediators of the nitrergic neurotransmission to the musculature in the small
intestine, playing a role in the regulation of intestinal movement.
PMID- 10189111
TI - Arterial tonometry in the measurement of the effects of innocuous mechanical
stimulation of the neck on heart rate and blood pressure.
AB - Arterial tonometry was used to continuously monitor the effects on heart rate and
blood pressure of a series of innocuous mechanical stimuli applied to the neck in
conscious humans. The stimuli used were derived from procedures commonly employed
in clinical examination and physical therapy of the neck. In alert subjects, the
stimuli used generally caused small and sometimes statistically significant
decreases in heart rate, systolic pressure and diastolic pressure. In alert
subjects, statistically significant decreases in systolic and diastolic pressure
were particularly associated with stimuli which involved full rotation of the
neck. In the course of the prolonged series of stimuli, some subjects slept or
reported being on the verge of sleep. In these subjects, the same stimuli
produced mixed effects on heart rate and increases in systolic and diastolic
pressure which were significantly different from the effects obtained in fully
alert subjects.
PMID- 10189110
TI - Nitric oxide inhibits the positive chronotropic and inotropic responses to
sympathetic nerve stimulation in the isolated guinea-pig atria.
AB - This study was designed to determine whether nitric oxide (NO) modulates the
positive chronotropic and inotropic (in paced atria) responses to cardiac
sympathetic nerve stimulation (SNS) in the isolated guinea-pig double
atrial/right stellate ganglion preparation. The ganglion was stimulated at 1, 2,
3 and 5 Hz at constant voltage and the changes in heart rate or force of
contraction were measured. The selective neuronal NO synthase (nNOS) inhibitors
TRIM (1-(2-trifluoromethylphenyl) imidazole; 100 microM) and 7-NiNa (Na+ salt of
7-nitroindazole; 100 microM) significantly enhanced the positive chronotropic and
inotropic responses to SNS. Similar results for heart rate were seen with the non
isoform-selective NOS inhibitor N(omega)nitro-L-arginine (L-NA; 100 microM). All
effects were reversed with L-arginine (1 mM). The NO donor sodium nitroprusside
(SNP; 100 microM) increased baseline heart rate and force of contraction, and
attenuated the positive chronotropic and inotropic responses to SNS. SNP also
decreased the positive chronotropic response to bath-applied noradrenaline (NA; 1
microM). In contrast, 7-NiNa did not alter the increase in heart rate with bath
applied NA (0.1 or 1 microM). The guanylyl cyclase inhibitor ODQ (10 microM)
enhanced (mimicking nNOS inhibition) and the cyclic GMP (guanosine 3':5'-cyclic
monophosphate) analogue 8-Br-cGMP (8-bromoguanosine 3':5'-cyclic monophosphate; 1
mM) attenuated (mimicking exogenous NO) the positive inotropic response to SNS.
Taken together, these results are consistent with endogenous NO, synthesized from
nNOS, inhibiting the positive chronotropic and inotropic responses evoked by
cardiac SNS via a cyclic GMP-dependent pathway.
PMID- 10189112
TI - Effects of 7-nitroindazole on renal sympathetic nerve activity during acute
cardiac tamponade in conscious rabbits.
AB - To investigate whether nitric oxide (NO) in the central nervous system is
involved in the decrease in renal sympathetic nerve activity (RSNA) during acute
cardiac tamponade in conscious rabbits, we examined the effect of 7-nitroindazole
(7-NI), a selective inhibitor of neuronal nitric oxide synthase in vivo, on RSNA
during acute cardiac tamponade in chronically installed conscious rabbits.
Cardiac tamponade was produced by intrapericardial infusion of physiological
saline at 2 ml/30 s. Mean arterial pressure (MAP) remained constant initially but
RSNA increased to 218+/-24% when we started injection of physiological saline
into the pericardial space. Concomitantly after MAP fell to 51+/-1 mm Hg by
subsequent injection of the saline into the pericardial space, RSNA decreased to
45+/-6%. If 7-NI (50 mg/kg) was administered intraperitoneally 35 min before the
beginning of cardiac tamponade, the decline in RSNA caused by cardiac tamponade
was markedly counteracted. Brain nitric oxide synthase (NOS) activity in the
cerebral cortex and medulla oblongata, assessed by the conversion of labelled
arginine to citrulline, was inhibited by 48% and 44% after the intraperitoneal
administration of 7-NI. These results indicate that acute cardiac tamponade
elicits a biphasic effect on RSNA, which rises during non-hypotensive period and
then falls during hypotension in conscious rabbits. The decrease in RSNA was
abolished by treatment with 7-NI, suggesting that the abrupt decrease in RSNA
during hypotension induced by acute cardiac tamponade is mediated by NO in the
central nervous system.
PMID- 10189113
TI - Mechanism of cholecystokinin-induced relaxation of the rat stomach.
AB - This study was designed to investigate the mechanism(s) and the site(s) of action
of cholecystokinin (CCK) responsible for the smooth muscle relaxation of the rat
stomach. Under xylazine and ketamine anesthesia, an extraluminal force transducer
was implanted on the serosal surface of the gastric body to monitor the circular
muscle motility. CCK8 (1-100 pmol, i.v.) caused predominantly inhibitory effects
(65%) on gastric motility but sometimes no effect (20%), excitatory effects (10%)
or biphasic effects (5%) were observed in 125 rats tested. CCK8 consistently
caused relaxation in rats pretreated with yohimbine, while CCK8 caused
contraction in rats pretreated with propranolol. CCK8-induced relaxation in the
presence of yohimbine was abolished by pretreatment with guanethidine, 6
hydroxydopamine, celiac ganglionectomy and hexamethonium but not by VIP antiserum
or a nitric oxide (NO) inhibitor. CCK8-induced relaxation was significantly
reduced by perineural capsaicin treatment of the celiac ganglia or vagal trunk.
Subsequent truncal vagotomy had no effect on CCK8-induced relaxation in rats with
perivagal capsaicin treatment, but completely abolished CCK8-induced relaxation
in rats with capsaicin treatment of the celiac ganglia. Our present study
suggests that CCK8 predominantly stimulates vagal and splanchnic afferents,
resulting in vago-splanchnic and splanchno-splanchnic reflexes. Released
catecholamine from splanchnic efferents by CCK8 can induce both excitatory and
inhibitory reflexes via alpha2 and beta adrenergic receptors located on gastric
smooth muscle cells, respectively. These finding may explain some of the variable
results reported for the actions of CCK8 on gastric motility.
PMID- 10189114
TI - Catecholamines in paraganglia associated with the hepatic branch of the vagus
nerve: effects of 6-hydroxydopamine and reserpine.
AB - Paraganglia are clusters of cells containing catecholamines (CA), mainly
norepinephrine (NE) and dopamine (DA). The presence of epinephrine (E), on the
other hand, has only been determined by indirect methods in retroperitoneal
paraganglia of newborn and aged rats. Because their location, paraganglia
associated with the hepatic branch of the vagus nerve may be a possible source of
CA for the liver. The main purposes of the present study were to determine CA
levels and whether E can be found in the omentum minus which includes paraganglia
associated with the hepatic branch of the vagus nerve, and then to study the
effects of 6-hydroxydopamine and reserpine on their CA content. Twenty-four
female Wistar rats were randomly ascribed to three groups receiving two
intraperitoneal injections of either 6-hydroxydopamine, reserpine or saline.
Twenty-four hours after the last administration the rats were anesthetized and a
portion of the omentum minus was obtained. Left adrenal medulla and a liver
fragment were also collected as controls. The samples were processed to be
analyzed by high performance liquid chromatography and catecholamine
histofluorescence. The results confirm previous reports about the presence of
considerable amounts of norepinephrine and dopamine in paraganglia.
Norepinephrine and dopamine in the omentum like the adrenal medulla were
significantly depleted by reserpine but not by 6-hydroxydopamine treatment,
suggesting that some other sources in addition to sympathetic terminals are
responsible for CA in the omentum. On the contrary, both drugs reduced liver NE,
consistent with the localization of this amine mainly to hepatic sympathetic
terminals. Histofluorescence of the omentum revealed 2-4 paraganglia per tissue
fragment. Paraganglia associated with the hepatic branch of the vagus nerve
contain also E. The presence of perihepatic sources of extra-adrenal CA, and more
specifically E, could be of physiological significance.
PMID- 10189115
TI - Neuronal nitric oxide facilitates vagal chronotropic and dromotropic actions on
the heart.
AB - Previous studies, using non-specific nitric oxide synthase (NOS) inhibitors, have
shown that nitric oxide (NO) has a significant facilitatory effect on the actions
of the vagus nerve on several aspects of cardiac function. The present study aims
to identify a potential neuronal site for the action of NO by using the n-NOS
inhibitor, 1-(2-trifluoromethylphenyl) imidazole (TRIM) in the ferret and other
mammals. The effects of TRIM on vagally evoked alterations in heart rate and
atrio-ventricular (a-v) conduction in the anaesthetised ferret, rabbit and guinea
pig are described. In ferrets with both vagi sectioned and repeated infusions of
propranolol, the vagally evoked, frequency-dependent bradycardia was
significantly attenuated by infusion of TRIM (10-30 mg kg(-1)). This effect was
reversed by subsequent infusion of L-arginine (20-6 mg kg(-1)). TRIM also
attenuated to a similar extent the vagally evoked bradycardia in similarly
prepared guinea pigs, but NOS inhibition and the use of the NO donor,
molsidimine, failed to alter the heart rate effects of vagal stimulation in the
rabbit. In studies on a-v conduction (dromotropy) in the ferret, electrical
stimulation of the left cervical vagus increased the a-v conduction time in a
frequency-dependent manner. Administration of TRIM (30 mg kg(-1)) significantly
attenuated this response. Again, L-arginine (60 mg kg(-1)) reversed it. Since an
alteration in heart rate may have a concomitant action on a-v conduction time,
the effects of vagal stimulation on a-v conduction were also carried out in
ferrets with the heart paced at a constant rate electrically. There was no
significant difference between the effects of vagal stimulation obtained from
hearts which were paced and those which were unpaced. This implies that vagal
stimulation had a direct effect on a-v delay and the changes were not secondary
to alterations in cardiac rate. Based on other evidence that TRIM is a powerful
reversible n-NOS inhibitor in vivo, our studies support strongly the hypothesis
that NO liberated from neuronal sources has an important facilitatory action on
the vagal control of the heart. In relation to vagal heart rate control, it has
now been shown that, in line with other studies in the dog and the rat, NO exerts
a powerful facilitatory action in the ferret and the guinea pig but not in the
rabbit. It is to be expected that these effects of NO will also be demonstrable
on other vagal cardiac actions.
PMID- 10189116
TI - P2X (purinergic) receptor distributions in rat blood vessels.
AB - The distribution of purinergic (P2X1 and P2X2) receptors on smooth muscle cells
in relation to autonomic nerve varicosities in rat blood vessels has been
determined using immunofluorescence and confocal microscopy. P2X1 and P2X2
receptors were visualised using rabbit polyclonal antibodies against the
extracellular domain of the receptors and varicosities visualised using a mouse
monoclonal antibody against the ubiquitous synaptic vesicle proteoglycan SV2. Two
size classes of P2X1 receptor clusters were observed on the smooth muscle cells
of mesenteric, renal, and pulmonary arteries as well as in the aorta and in
veins: a large approximately elliptical cluster 1.32+/-0.21 microm long and
0.96+/-0.10 microm in diameter; and a smaller spherical cluster with a diameter
of 0.32+/-0.05 microm. The latter occurred throughout the media of arteries of
all sizes, whereas the former were restricted to the adventitial surface of the
media and to endothelial cells, except for the pulmonary artery, in which large
receptor clusters were found throughout the media of the vessel. At the
adventitial surface, the large clusters are in general located beneath SV2
labelled varicosities. None of the small clusters was associated with
varicosities. Three-dimensional reconstruction of the P2X and SV2 labelling at
individual varicosities showed that the varicosities were immediately apposed to
the P2X receptor clusters. P2X2 receptors were located on nerves and on
endothelial cells. They were also found in low density on the smooth muscle cells
in the media. These observations are discussed in relation to the mechanism of
purinergic transmission to the smooth muscle cells of blood vessels.
PMID- 10189117
TI - Gamma-aminobutyric acid-induced responses in acutely dissociated neurons from the
rat sacral dorsal commissural nucleus.
AB - The electrophysiological and pharmacological properties of GABA-activated Cl-
currents (IGABA) were investigated in enzymatically dissociated rat sacral dorsal
commissural nucleus (SDCN) neurons using the nystatin perforated patch recording
configuration under voltage-clamp conditions. Exogenous application of GABA to
SDCN neurons induced Cl- currents which increased in a concentration-dependent
manner. Bicuculline (BIC) and strychnine (STR) antagonized the IGABA in a
concentration-dependent manner. Zn2+ suppressed the IGABA with an IC50 of 2.8 X
10(-5) M. Muscimol mimicked the IGABA, while baclofen evoked no response.
Pentobarbital (PB) and 5beta-pregnan-3alpha-ol-20-one (pregnanolone, PGN) also
induced GABAA-mimic Cl- currents. Diazepam (DZP), PB and PGN all enhanced the
IGABA by increasing the apparent affinity of the GABAA receptors to GABA.
Moreover, spontaneous GABAergic inhibitory postsynaptic currents (IPSCs) were
observed in mechanically dissociated SDCN neurons attached with synaptic boutons,
so called 'synaptic bouton preparation'. These results indicate that SDCN neurons
express GABAA receptors with relatively low sensitivity to Zn2+ inhibition, and
that GABA may have a functional role as an inhibitory transmitter in the SDCN
regulating nociceptive, analgesic, and autonomic functions.
PMID- 10189118
TI - Non-invasive assessment of human baroreflex during different body positions.
AB - Two techniques for evaluating human baroreflex sensitivity (BRS), i.e. the
sequence technique and the cross-spectral technique, were compared during the
following four different body positions; 6 degrees head-down tilt (HDT), supine
(Sup), 60 degrees head-up tilt (HUT) and upright (Upr). The sequence technique is
based on the slope of linear regression between beat-to-beat RR intervals and
systolic blood pressures. The cross-spectral technique is based on the cross
spectral analysis of RR interval and systolic blood pressure variabilities, and
the estimates of BRS were computed separately for the low-frequency region (0.04
0.15 Hz) and the high-frequency region (0.15-0.5 Hz). The BRS obtained by the
sequence technique had a significant correlation to that obtained by the cross
spectral technique for the low-frequency region in HDT, Sup and HUT, but not in
Upr. There was a significant correlation between the BRS obtained by the sequence
technique and that obtained by the cross-spectral technique for the high
frequency region in every body position. It became clear that the sequence
technique is mutually related to the cross-spectral technique for the high
frequency region, but not necessarily identical to the cross-spectral technique
for the low-frequency region. Moreover, a comparison was also made between the
baroreceptor activating sequence and the deactivating sequence in the sequence
technique during the four different body positions. Although the estimates of BRS
of the activating sequence and the deactivating sequence were similar in every
body position, the numbers of their sequences were progressively separated in the
order of HDT, Sup, HUT and Upr. The numbers of the activating sequence and the
deactivating sequence in the sequence technique were found to be separated in a
sympathetically dominant condition.
PMID- 10189119
TI - Sympathetic-parasympathetic interactions at the heart in the anaesthetised rat.
AB - This study observed the effects of stimulation of the cardiac sympathetic nerve
on vagal slowing of the heart in rats, and compared these with any actions of
exogenous neuropeptide Y (NPY) and galanin (GAL). In rats anaesthetised with
pentobarbitone, stimulation of the cardiac sympathetic nerve for 2 min at 20 Hz
in the rat evoked an attenuation of subsequent cardiac vagal action, which could
be mimicked by exogenous NPY, but not GAL. The galanin antagonist, GAL1-13/NPY24
36, known to block the inhibitory action of galanin on the cardiac vagus in cats,
did not alter the effect of sympathetic stimulation on cardiac vagal activity. We
suggest on the basis of results here that in the rat, NPY released during
stimulation of the cardiac sympathetic nerve, causes inhibition of acetylcholine
release from the vagus nerve.
PMID- 10189120
TI - Basic emotions induced by odorants: a new approach based on autonomic pattern
results.
AB - The aim of this study was to link the effects of odorants with the emotional
process, through autonomic nervous system (ANS) responses. Taking Ekman's data
and our previous results into account, we tried to verify a possible evocation by
odorants of some basic emotions, i.e. anger, fear, sadness, surprise, disgust and
happiness. The question investigated was: would it be possible to associate any
of these emotions with a pattern of autonomic responses? A total of 15 subjects
inhaled five odorants: lavender, ethyl aceto acetate, camphor, acetic acid and
butyric acid acting as olfactory stimuli. After inhaling the odorant, subjects
were requested to fill out an 11-point hedonic scale to rate its 'pleasantness'
vs. 'unpleasantness'. ANS parameters monitored were skin potential and
resistance, skin blood flow and temperature, instantaneous respiratory frequency
and instantaneous heart rate. Simultaneous recording of these six autonomic
parameters permitted the analysis of phasic responses through specific ANS
patterns. An analysis of variance made it possible to differentiate among the
five odorants. Two-by-two odorant comparisons for autonomic responses using
Tukey's HSD multiple comparison test only permitted differentiation between
'pleasant' and 'unpleasant' odors. Camphor was differentiated from both types.
For instance, long duration responses were associated with 'unpleasant' odors
whereas camphor elicited intermediate responses. Taking into account each
subject's preferential channel, it was possible to associate each ANS pattern
with a basic emotion by means of a decision tree. The computation of subjects'
responses made it possible to associate an odorant with a basic emotion, over the
whole group: lavender elicited mostly 'happiness', as did, to a lesser degree
ethyl aceto acetate; camphor induced either 'happiness', 'surprise' or 'sadness'
according to subjects' past histories; butyric and acetic acids mainly induced
negative emotions: 'anger' and 'disgust'. A high correlation was evidenced
between subjects' hedonic evaluation and autonomic estimation of basic emotions.
These results obtained from 15 subjects were compared to those observed in two
similar experiments. These approaches showed comparable results. Thus, more than
60 subjects showed similar autonomic responses which can be transcribed into
basic emotions. Thus, a multiparametric autonomic analysis allows the
identification of the quality of the response, i.e. the type of basic emotion in
addition to the intensity.
PMID- 10189121
TI - Superior mesenteric artery dilatation alone does not account for glucose-induced
hypotension in human sympathetic denervation.
AB - Haemodynamic and hormonal effects of two oral isovolaemic, isoosmotic solutions
of 0.5 g/kg and 1.0 g/kg glucose were studied in 10 humans with sympathetic
denervation due to primary autonomic failure (AF). Measurements were made supine
for 60 min, and also after 5 min 45 head-up tilt, before and 60 min after
glucose. There was a similar fall in blood pressure (BP) after each dose, after
0.5 g/kg from 160+/-12 / 87+/-6 to 143+/-13 / 76+/-6 mm Hg, P < 0.05 and after
1.0 g/kg from 160+/-13 / 90+/-6 to 136+/-9 / 76+/-5 mm Hg, P < 0.05. Heart rate,
cardiac index and forearm muscle blood flow did not change after either dose.
After 0.5 g/kg, superior mesenteric artery blood flow was unchanged but rose
significantly after 1.0 g/kg, from 243 (169-395) to 722 (227-982) ml/min, P <
0.05, 15 min after ingestion. BP fell further on tilt 60 min after each dose, but
there was no difference between doses. Plasma glucose was higher after 1.0 g/kg
but plasma insulin was similar after each dose. Thus, in AF with sympathetic
denervation there was no dose-related effect of glucose on supine or postural
hypotension. Supine hypotension after glucose was not attributable solely to
increased splanchnic blood flow; other factors, including dilatation in other
vascular beds may have contributed.
PMID- 10189122
TI - Orthostatic intolerance in the chronic fatigue syndrome.
AB - This study aims to investigate the prevalence and pathophysiology of orthostatic
intolerance (OI) and its potential contribution to symptoms of a group of
unselected patients with chronic fatigue syndrome (CFS). Seventy five patients
(65 women, 10 men) with CFS were evaluated. During an initial visit, a clinical
suspicion as to the likelihood of observing laboratory evidence of OI was
assigned. Laboratory investigation consisted of beat-to-beat recordings of heart
rate, blood pressure (Finapres), and stroke volume (impedance cardiograph) while
supine and during 80 degrees head-up tilt (HUT), during rhythmic deep breathing
(6 breaths/min) and during the Valsalva maneuver. The responses of 48 age-matched
healthy controls who had no history of OI were used to define the range of normal
responses to these three maneuvers. Forty percent of patients with CFS had OI
during head-up tilt. Sixteen exhibited neurally-mediated syncope alone, seven
tachycardia (> 35 bpm averaged over the whole of the head-up tilt) and six a
mixture of tachycardia and syncope. Eight of 48 controls exhibited neurally
mediated syncope. The responses to the Valsalva maneuver and to deep breathing
were similar in controls and patients. On average, the duration of disease and
patient age were significantly less and the onset of symptoms was more often
subacute in patients with OI than in those without OI. We conclude that there
exists a clinically identifiable subgroup of patients with CFS and OI that
differs from control subjects and from those with CFS without OI for whom
treatment specifically aimed at improving orthostatic tolerance may be indicated.
PMID- 10189123
TI - Comparison of the sympathetic skin response and continuous wave Doppler
sonography of the radial artery.
AB - The value of neurophysiological tests of the autonomic nerve system is limited.
One of the clinically most commonly applied test is the skin sudomotor response,
frequently referred to as 'sympathetic skin response' (SSR). However, the SSR is
a more qualitative than quantitative evaluation technique. Continuous wave (cw)
Doppler sonography of the radial artery may be an alternative quantitative
approach. We studied 41 age matched volunteers (23 female, 18 male; 16-82 years
(mean age 53 years)). The stimulus was a loud and unexpected acoustic signal,
alternatively a cough. SSR evaluation included the latency of onset, the duration
and the amplitude of the response. Doppler evaluation also included flow velocity
and resistance index (RI) changes with adequate stimulation. SSRs were observed
in 36 volunteers (88%), Doppler responses in 35 (85%). The latency between
stimulus and response onset was 1.35 s with SSR and 1.52 s with ultrasound
(n.s.). The mean SSR amplitude was 1.3 mV, systolic velocities decreased by 20%
and diastolic velocities by 124% (flow reversal). RI increased from 0.85 to 1.25
with no correlation between SSR amplitude and flow velocity changes. SSR and cw
Doppler are complementary methods. Doppler sonography offers an additional
approach of autonomic nerve evaluation.
PMID- 10189124
TI - Phase II clinical trial of 13-cis-retinoic acid and interferon-alpha-2a in
patients with advanced esophageal carcinoma.
AB - BACKGROUND: Interferon in combination with 5-fluorouracil has been shown to be
active in squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the esophagus.
13-cis-retinoic acid (CRA) has chemopreventive activity in SCC of the head and
neck, and, in combination with interferon, has antitumor activity in SCC of the
skin and cervix. METHODS: The activity and toxicity of CRA and interferon-alpha
2a (IFN) in patients with advanced esophageal carcinoma was evaluated in a Phase
II single institution trial. Patients had unresectable or metastatic AC or SCC of
the esophagus. One prior chemotherapy regimen was allowed. IFN was given by daily
subcutaneous injection at a dose of 3 million U and CRA was taken orally at a
dose of 1 mg/kg/day in 2 divided doses. Treatment was given in cycles of 4 weeks
and continued until documented disease progression. RESULTS: Of the 19 patients
entered, 15 were evaluable for response and toxicity. One patient was evaluable
for response only and one patient was evaluable for toxicity only. Evaluable
patients were predominantly male (15 patients), and had AC (13 patients). All had
AJCC Stage IV disease and 12 were pretreated. Patients completed an average of
two cycles of therapy (range, one to six cycles) prior to progression of disease.
National Cancer Institute Common Toxicity Criteria Grade 3/4 toxicity was notable
for nausea (25%) and fatigue (31%). No major objective responses were recorded.
Eleven patients with AC and 3 patients with SCC had rapid progression of disease.
One patient with AC was found to have a minor response for 22 weeks and 1 patient
with AC had stable disease for 45 weeks. CONCLUSIONS: This regimen had no
significant activity in patients with advanced AC of the esophagus. Further
evaluation of IFN plus CRA, using this dose and schedule, is not recommended. In
comparison with prior trials of this therapy, a surprising amount of severe
nausea and fatigue was observed in this trial.
PMID- 10189125
TI - Iodine-125 brachytherapy in the treatment of colorectal adenocarcinoma metastatic
to the liver.
AB - BACKGROUND: The liver is the site of distant failure in > 33% of patients with
colorectal adenocarcinoma. Liver resection is the only potentially curative
option in these patients. Patients with incompletely resected liver lesions (due
to the proximity to critical vascular structures) are at high risk of dying of
progressive disease in the liver. This pilot study was performed to determine
whether the intraoperative implantation of iodine-125 (I-125) seeds could reduce
the recurrence and improve the survival of patients with incompletely resected
liver metastases. METHODS: Fifty-six patients with unresectable or residual
disease after surgical resection of liver metastases from colorectal carcinoma
underwent permanent implantation with I-125 seeds to deliver 160 gray to the
periphery of the target volume. RESULTS: The 1-, 3-, and 5-year actuarial control
rates of liver disease were 41%, 23%, and 23%, respectively. The 5-year actuarial
control of liver disease was better for patients with a solitary metastasis (39%)
than for those with multiple metastases (9%) (P = 0.04). The 1-, 3-, and 5-year
actuarial overall survival rates were 71%, 25%, and 8%, respectively (median, 20
months; 95% confidence interval, 17-23). The radiation-related complications were
minimal. CONCLUSIONS: I-125 liver brachytherapy is feasible with minimal
radiation-related morbidity. Good prognostic factors for long term liver control
and survival are the presence of a solitary metastasis, postresection minimal
residual disease requiring smaller volume implants, and no prior liver
resections. Future prospective trials should be directed toward this patient
population, which has the highest probability of obtaining improved results from
the local dose escalation provided by brachytherapy. Adjuvant regional
chemotherapy clearly is needed due to the high rate of liver recurrence and
ultimate death from liver failure observed in spite of liver resection and
brachytherapy.
PMID- 10189126
TI - Overexpression of p53 protein and outcome of patients treated with chemoradiation
for carcinoma of the anal canal: a report of randomized trial RTOG 87-04.
Radiation Therapy Oncology Group.
AB - BACKGROUND: Despite encouraging results with chemoradiation as the primary means
of managing carcinoma of the anal canal, approximately 20% of patients will
develop a local recurrence. This study examined the prognostic significance of
p53 nuclear protein overexpression in the pretreatment biopsies of patients
treated with chemoradiation for epidermoid carcinoma of the anal canal. METHODS:
All patients were treated in a prospective, randomized Radiation Therapy Oncology
Group trial (RTOG 87-04) in which radiotherapy to the pelvis was compared with
concurrent 5-fluorouracil (5-FU) or 5-FU and mitomycin-C. Formalin fixed,
paraffin embedded blocks or unstained slides from the pretreatment biopsies of 64
patients were obtained from referring institutions and evaluated
immunohistochemically with the polyclonal p53 antibody CM-1. A multivariate
analysis was conducted to analyze overexpression of p53 in terms of locoregional
control, no evidence of disease (NED), and overall survival. RESULTS: p53 protein
was overexpressed in 48.4% of the cases. Although not statistically significant,
there was a trend for patients whose tumors overexpressed p53 to have inferior
locoregional control (52% vs. 72%, P = 0.13), NED survival (52% vs. 68%, P =
0.27), and absolute survival (58% vs. 78%, P = 0.14). Of all the pretreatment
factors analyzed, only International Union Against Cancer stage was predictive of
outcome in multivariate analysis. Among those patients whose tumors overexpressed
p53, there was a trend toward improved outcome in the arm that received 5-FU and
mitomycin-C compared with the arm that received 5-FU only. CONCLUSIONS:
Overexpression of the p53 protein may be associated with inferior outcome for
patients managed with definitive chemoradiation for epidermoid carcinoma of the
anal canal.
PMID- 10189127
TI - Expression of the MAGE gene family in human hepatocellular carcinoma.
AB - BACKGROUND: The 12 members of the MAGE gene family encode tumor specific antigens
that are recognized by autologous cytotoxic T lymphocytes (CTL). The MAGE genes
are expressed not only in melanoma but in the other malignant tumors as well.
There is, however, little information on their expression in hepatocellular
carcinoma (HCC). The authors thus studied the expression of the MAGE gene family
in human HCC and discuss the possibility of specific immunotherapy using MAGE
peptides. METHODS: Tumor tissue samples of HCC and paired nontumor tissues of the
liver were obtained from 22 HCC patients. Total RNA was extracted and cDNA was
synthesized. Polymerase chain reaction amplification using each MAGE gene
specific primer was then performed to detect the expression of each MAGE gene.
Immunoblotting and immunohistochemical analysis were performed to confirm the
expression of MAGE-3 gene product in HCC. RESULTS: The expression rate of each
MAGE gene was as follows: MAGE-1 and -3 were expressed in approximately 68% of
the tumors; MAGE-8 was expressed in 46%; and MAGE-2, -6, -10, -11, and -12 were
expressed in approximately 30%. Nineteen (86%) of 22 tumors expressed at least 1
MAGE gene. On the other hand, no expression was detected in the noncarcinomatous
liver tissue specimens. Actual expression of the gene product of MAGE-3 was
detected in 50% of tumors. Clinicopathologic data on the MAGE positive and
negative cases were compared. Significant differences were observed between MAGE
expression status and a few clinicopathologic factors; however, further
investigation is required to elucidate these correlations completely.
CONCLUSIONS: These findings demonstrated that MAGE gene expression is frequent in
HCC, thus suggesting that HCC patients may be good candidates for specific
immunotherapy using MAGE peptides.
PMID- 10189128
TI - Carcinoid tumors of the ampulla of Vater: a comparison with duodenal carcinoid
tumors.
AB - BACKGROUND: Although ampullary carcinoid tumors (ACs) are often categorized
clinically as duodenal carcinoid tumors (DCs), there are distinct clinical and
pathologic differences. METHODS: Clinical, histopathologic, and
immunohistochemical features of 12 ACs were compared with those of 53 DCs that
did not involve the ampulla. RESULTS: Patients with AC were ages 28-74 years
(mean, 54.9 years); 8 were males and 4 were females. Five were white and three
were black; the race of four patients was not known. The size of ACs ranged from
0.2 to 5.0 cm in greatest dimension. There were no significant differences
between AC patients and DC patients with respect to male predominance, race,
tumor size, and mitotic rate. The insular growth pattern was more common in AC;
the cribriform type was more common in DC. Four of 12 ACs contained psammoma
bodies, versus none of 53 DCs (P = 0.001). The rate of metastasis was similar in
patients with AC (4 of 12, 33%) compared with DC patients (14 of 53, 26%). In DC
patients, involvement of the muscularis propria, a size greater than 2 cm, and
mitotic activity were significantly correlated with metastatic risk. In AC
patients, tumor size and mitotic activity had no correlation with metastatic
potential. One AC had features of an atypical carcinoid tumor; there were none in
the duodenal group. One-half of patients with AC presented with jaundice versus
7% of patients with DC (P = 0.005). Three patients (25%) with AC had von
Recklinghausen disease versus 0 of 53 patients with DC (P = 0.003).
Immunohistochemically, tumor cells expressed somatostatin in 67%, serotonin and
cholecystokinin in 17%, insulin in 25%, and glucagon and gastrin in 0% of ACs. In
contrast, 56% of DCs expressed gastrin (P < 0.001). CONCLUSIONS: Carcinoid tumors
of the ampulla differ clinically, histologically, and immunohistochemically from
carcinoid tumors elsewhere in the duodenum.
PMID- 10189130
TI - An investigational new drug treatment program for patients with gemcitabine:
results for over 3000 patients with pancreatic carcinoma.
AB - BACKGROUND: An Investigational New Drug (IND) treatment program allows patients
access to a drug that has shown activity against a serious or life-threatening
disease prior to full Food and Drug Administration (FDA) review and approval.
This treatment IND program, in which patients with locally advanced or metastatic
pancreatic carcinoma were treated with gemcitabine, began in 1995. METHODS:
Eligibility criteria were < or =1 prior chemotherapy regimen; a Karnofsky
performance status (KPS) of > or =50; and adequate bone marrow, liver, and renal
function. Gemcitabine was given at a dose of 1000 mg/m2 weekly x 7 followed by a
week of rest, then weekly x 3 every 4 weeks thereafter. In this program, disease
related symptom improvement (DRSI) was defined retrospectively as 1) improvement
in pain (on a 7-point scale) and/or analgesic class (e.g., morphine improving to
codeine) and/or KPS (> or =20 points), or 2) stability of these three parameters
with a 7% increase in weight from baseline. RESULTS: A total of 3023 patients
enrolled. At baseline, 80% of them had Stage IV disease, and 84% had a baseline
KPS > or = 70. The median age was 65 years, and 56% of the patients were male.
The cumulative DRSI response rate after the fourth cycle was 18.4%. Of 982
patients with tumor response data, there were 14 with complete response and 104
with partial response, for an overall response rate of 12.0% (95% confidence
interval [CI], 10.0-14.0%). For 2380 patients with survival data, the median
survival was 4.8 months (95% CI, 4.5-5.1 months) and the 12-month survival was
15%. Gemcitabine was well tolerated; only 4.6% of discontinuations were due to
adverse events. CONCLUSIONS: Notable disease-related symptom improvement and
survival were seen with gemcitabine in this large, compassionate-use setting, and
these findings were in agreement with those of earlier registration trials.
PMID- 10189129
TI - Loss of p27Kip1 expression independently predicts poor prognosis for patients
with resectable pancreatic adenocarcinoma.
AB - BACKGROUND: As a universal inhibitor of cyclin-dependent kinases in mammalian
cells, p27Kip1 expression has been implicated in tumor progression and has proved
to be a prognostic predictor for several human cancers. In this study, the
authors investigated the expression of p27Kip1 and its potential prognostic
significance in patients with resectable pancreatic adenocarcinoma. METHODS: The
correlation between p27Kip1 expression and prognosis was investigated
retrospectively in 38 patients who had undergone resection of pancreatic
adenocarcinoma including 2 cystadenocarcinomas and 4 mucin-producing tumors.
Immunohistochemical staining using an anti-p27Kip1 antibody, along with an
assessment of tumor cell Ki-67 labeling index, was performed on resected
specimens. RESULTS: p27Kip1 expression in pancreatic adenocarcinoma was decreased
dramatically when compared with that in normal pancreatic tissue. Based on 35
cases available for survival analysis, loss of p27Kip1 expression in 16 cases
defined as having no or <1% p27Kip1 positive tumor cells showed 1-, 1.5-, and 2
year survival rates of 37.5%, 15.6%, and 0%, respectively, in comparison with 1-,
2-, and 3-year survival rates of 68.4%, 62.2%, and 49.8%, respectively, in the
other cases (P = 0.001). After excluding cases of cystadenocarcinoma and mucin
producing tumors, the survival advantage for patients with p27Kip1 positive
tumors remained apparent (P = 0.024). In each Cox regression model, both those
including cystadenocarcinoma and mucin-producing tumors and those that did not,
p27Kip1 expression proved to be an independent predictor for overall survival by
multivariate analysis. CONCLUSIONS: These results reveal the significance of
p27Kip1 immunostaining in predicting the outcome of patients with resectable
pancreatic adenocarcinoma, adding a novel predictor in the evaluation of
prognosis for this lethal disease.
PMID- 10189132
TI - Estrogen replacement therapy in women with a history of proliferative breast
disease.
AB - BACKGROUND: Little information is available regarding the invasive breast
carcinoma risk associated with estrogen replacement therapy (ERT) in women with
histories of histologically defined breast lesions. METHODS: A retrospective
cohort study of a consecutive series of women who underwent breast biopsies that
proved to be benign between 1952-1978 was conducted. Follow-up data were obtained
for 9494 women (87.6% of women eligible for follow-up). To investigate the effect
of ERT on invasive breast carcinoma risk, the analysis was restricted to women
with premenopausal breast disease whose follow-up extended through menopause and
who did not develop premenopausal breast carcinoma. Relative risks were
calculated with respect to women who took ERT but whose benign breast biopsies
had neither atypical hyperplasia (AH), complex fibroadenoma (CFA), nor
proliferative disease without atypia (PDWA). RESULTS: During 190,845 woman-years
of follow-up there were 444 confirmed cases of invasive breast carcinoma in the
entire cohort. Women with a history of AH had relative risks of invasive breast
carcinoma of 2.87 (95% confidence interval [95% CI], 1.3-6.3) and 2.53 (95% CI,
1.0-6.3) if they did or did not take ERT, respectively. For women with a history
of CFA these risks were 1.57 (95% CI, 0.72-3.4) and 1.46 (95% CI, 0.53-4.0),
respectively, whereas for women with a history of PDWA they were 1.37 (95% CI,
0.88-2.1) and 1.13 (95% CI, 0.69-1.9), respectively. CONCLUSIONS: ERT does not
significantly elevate the risk of invasive breast carcinoma in women with
previous histologically defined benign breast disease. Therefore, ERT is not
contraindicated in these women.
PMID- 10189131
TI - Phase I/II trial of paclitaxel by 1-hour infusion, carboplatin, and gemcitabine
in the treatment of patients with advanced nonsmall cell lung carcinoma.
AB - BACKGROUND: The combination of paclitaxel and carboplatin is widely used in the
treatment of patients with advanced nonsmall cell lung carcinoma. In this Phase
I/II study the authors evaluated the feasibility, toxicity, and efficacy of
adding a third active antineoplastic agent, gemcitabine, to the
paclitaxel/carboplatin combination for the treatment of patients with advanced
nonsmall cell lung carcinoma. METHODS: Patients with advanced (AJCC Stage IIIB or
IV) nonsmall cell lung carcinoma previously untreated with chemotherapy were
eligible for this trial. The maximum tolerated doses, determined in the Phase I
trial and subsequently used in the Phase II trial, were: paclitaxel, 200 mg/m2,
as a 1-hour infusion on Day 1; carboplatin, at area under the curve dose of 5.0
intravenously (i.v.), on Day 1; and gemcitabine, 1000 mg/m2 i.v., on Days 1 and
8. Treatment courses were repeated every 21 days. The Phase II study was
conducted in 13 community-based practices in the Minnie Pearl Cancer Research
Network; 77 patients were treated between December 1996 and September 1997.
RESULTS: Thirty-four of 77 patients (44%) in the Phase II trial had major
responses (partial responses, 32 patients and complete responses, 2 patients). An
additional 25 patients (33%) had stable disease or minor response; only 23% of
patients progressed or were removed from study at or prior to first reevaluation.
The median survival was 9.4 months, with a 45% actuarial 1-year survival rate.
Myelosuppression was the most common toxicity, with Grade 3/4 NCI Common Toxicity
Criteria leukopenia and thrombocytopenia in 49% and 45% of patients,
respectively. However, only 11 patients (14%) required hospitalization for
neutropenia/ fever, and none had bleeding complications. Grade 3/4 nonhematologic
toxicities included fatigue (41%), arthralgias/myalgias (26%), peripheral
neuropathy (8%), nausea/emesis (6%), and hypersensitivity reactions (4%). There
was one treatment-related death due to sepsis. CONCLUSIONS: This three-drug
regimen is active and has acceptable toxicity in patients with advanced nonsmall
cell lung carcinoma. Myelosuppression, particularly thrombocytopenia, is
increased in comparison to the paclitaxel/carboplatin regimen. Fatigue also may
be increased, but other nonhematologic toxicities are not altered substantially
by adding gemcitabine. Although the response rate and median survival are
improved modestly compared with our previous experience with
paclitaxel/carboplatin, definitive conclusions regarding the efficacy of this
regimen await the completion of randomized trials.
PMID- 10189133
TI - A randomized trial of tamoxifen alone or combined with octreotide in the
treatment of women with metastatic breast carcinoma.
AB - BACKGROUND: Tamoxifen (TAM) is generally considered the hormonal agent of choice
for postmenopausal women with hormone receptor positive breast carcinoma. The
somatostatin analogues, including octreotide, have demonstrated inhibition of
breast carcinoma cell lines and multiple endocrinologic actions, including
reduction of insulin-like growth factor I (IGF-I), a potent mitogen for breast
carcinoma cells. In an attempt to improve the efficacy of TAM, this randomized
trial was performed. METHODS: One hundred thirty-five eligible postmenopausal
women with metastatic breast carcinoma were randomized to TAM (10 mg twice daily)
alone or combined with octreotide 150 microg (administered subcutaneously thrice
daily). The two groups were well balanced, except the TAM group had higher
proportions of patients with visceral disease (50% vs. 37%) and a disease free
interval longer than 5 years (47% vs. 34%). A cohort of 18 patients was evaluated
for the impact of treatment on serum IGF-I, free IGF-I, IGF binding protein 3
levels, and total IGF binding capacity. RESULTS: The median time to progression
was estimated to be 14.2 months with TAM and 10.3 months with TAM plus
octreotide. The distribution of progression free survival times revealed no
significant difference (P = 0.26), and the progression hazard ratio (TAM/TAM +
octreotide) was 0.81 (95% confidence interval [CI], 0.56-1.17). The distribution
of survival times revealed no significant difference (P = 0.92), and the death
hazard ratio was 0.98 (95% CI, 0.62-1.55). When the 106 patients with measurable
or evaluable disease were considered, the objective response rate was 49% with
TAM alone and 43% with TAM plus octreotide (P = 0.70). Patients who received TAM
plus octreotide had higher incidences of nausea, diarrhea, and steatorrhea. The
percentage of decline in serum IGF-I, from pretreatment levels to those following
3-6 weeks of treatment, was significantly greater (P < 0.01) with TAM plus
octreotide than with TAM alone. CONCLUSIONS: There is no indication that the
combination of TAM plus octreotide as administered in this study is substantially
more efficacious than TAM alone in the treatment of postmenopausal women with
metastatic breast carcinoma. The limited cohort included in IGF-I studies
suggests that TAM plus octreotide produces a significantly greater reduction in
serum IGF-I levels.
PMID- 10189135
TI - Predictors of cancer progression in T1a prostate adenocarcinoma.
AB - BACKGROUND: The biologic behavior of T1a prostate adenocarcinoma is variable. A
critical issue in the management of patients with T1a prostate adenocarcinoma is
to distinguish those who will develop cancer progression from those who will not.
Predictive factors that identify those at high risk of cancer progression are
needed to stratify patients for treatment. In the current study the authors
attempted to identify such predictors of cancer progression in a large series of
untreated patients with lengthy follow-up. METHODS: The authors studied 102
patients who were diagnosed with T1a prostate adenocarcinoma (incidental tumor
involving < or = 5% of the resected prostatic tissue) at the time they underwent
transurethral resection of the prostate (TURP) at the Mayo Clinic between 1960
1970. None of these patients were treated. Patient ages ranged from 48-91 years
(mean +/- standard deviation, 69 +/- 7 years). The average weight of the resected
prostate tissue was 24 +/- 18 g (range, 3-115 g; median, 18 g). Tumor volume was
measured by the grid method. Cox proportional hazards models were used to
identify factors associated with cancer progression. Survival curves were
estimated using the Kaplan-Meier method. RESULTS: Five-year and 10-year
progression free survival rates were 93% and 87%, respectively. During the mean
follow-up of 9.5 +/- 6.8 years (range, 0.3-31 years; median, 9.0 years), 14
patients developed clinical cancer progression, including 5 patients with
systemic progression (1 with distant metastases and 4 who died of prostate
adenocarcinoma). The interval from diagnosis to clinical cancer progression
ranged from 1-23 years (mean, 7.3 years). The amount of resected prostate tissue
(TURP weight) was associated with progression (P = 0.04). Patients with a TURP
weight > or = 30 g had 100% progression free survival at 10 years compared with a
progression free survival rate of 73% in patients with a TURP weight < 12 g.
Gleason score, tumor volume, number of chips involved by tumor, number of tumor
foci, and the presence of high grade prostatic intraepithelial neoplasia were not
significant in predicting cancer progression. There was a trend toward a worse
prognosis with the increasing number of chips involved by cancer (P = 0.16).
Patients with < 3 chips involved by cancer had a 88% 10-year progression free
survival rate compared with 73% in patients with > or = 3 chips involved by
cancer. CONCLUSIONS: The clinical course of T1a prostate adenocarcinoma is
variable. If left untreated, a small but significant proportion of patients are
at risk for disease progression and death. However, the current study found that
patients with a TURP weight > or = 30 g have an excellent prognosis and can be
managed conservatively.
PMID- 10189134
TI - p53 protein overexpression is associated with increased cell proliferation in
patients with locally recurrent prostate carcinoma after radiation therapy.
AB - BACKGROUND: The biologic changes in recurrent prostate carcinoma following
radiation therapy are not fully understood. The authors sought to determine the
level of p53 protein overexpression and its association with cellular
proliferation (Ki-67 labeling index), glutathione S-transferase-pi (GST-pi)
expression, and other clinical pathologic findings in patients with locally
persistent prostate carcinoma after radiation therapy. METHODS: The authors
investigated p53 nuclear accumulation, cellular proliferation activity (Ki-67
labeling index by digital image analysis), and GST-pi expression in 55 patients
with persistent or recurrent prostate carcinoma after radiation therapy. All
patients underwent salvage radical prostatectomy and bilateral pelvic
lymphadenectomy following irradiation failure. The interval from radiation
therapy to cancer recurrence ranged from 6 months to 17 years (mean, 3.8 years).
Age at surgery ranged from 51 to 78 years (mean, 65 years). Mean follow-up after
surgery was 5.7 years (range, 1-13 years). RESULTS: p53 protein overexpression
was associated with increased cell proliferation (Spearman rank correlation
coefficient = 0.29, P = 0.03). A substantial proportion (62%) of recurrent cancer
also showed GST-pi immunoreactivity. No apparent correlation was observed between
p53 protein overexpression, cellular proliferation (Ki-67 labeling index), or GST
pi expression and Gleason score, pathologic stage, DNA ploidy, or patient
outcome. There was an inverse correlation between GST-pi expression and Gleason
score (P = 0.06). The majority of prostate carcinomas (95%) were proliferative
(mean Ki-67 labeling index, 7.0; range, 0-20), whereas concurrent prostatic
intraepithelial neoplasia (PIN) had a lower Ki-67 labeling index (mean, 3.1;
range, 0-11.5). Nineteen of 28 (68%) concurrent PIN demonstrated p53
immunoreactivity. A trend toward adverse clinical outcome was observed in
patients with a higher Ki-67 labeling index in recurrent cancer. CONCLUSIONS: In
this study cohort selected for salvage prostatectomy, recurrent cancers were
biologically aggressive following radiation therapy. Whether this represents
selective persistence and regrowth of prognostically unfavorable tumor clonogens
or stepwise clonogenic progression is uncertain. Further investigation is needed
to elucidate the correlation between p53 overexpression and the presence of other
biologic changes after radiation therapy.
PMID- 10189136
TI - Demographics, family histories, and psychological characteristics of prostate
carcinoma screening participants.
AB - BACKGROUND: The goals of this study were to 1) understand the reasons that men
seek prostate carcinoma screening, in light of the ongoing medical controversy
surrounding screening; and 2) assess the level of psychological distress and
perceived risk among men seeking screening, and whether or not these variables
were dependent on a man's family history of prostate carcinoma. METHODS: The
subjects were 126 men (40% had a family history of prostate carcinoma) who
participated in a free prostate carcinoma detection program. Questionnaires,
which were completed prior to prostate carcinoma screening, included demographic
and medical information, reasons for screening participation, general and cancer
related psychological distress, and perceived risk for prostate carcinoma.
RESULTS: Among both family history groups, self-referral was the most common
reason for attending the screening, compared with receiving a recommendation from
a health professional or from a friend or family member. Men with a positive
family history were not more distressed than those without a family history; but
as the authors predicted, men with a positive family history of prostate
carcinoma did report higher levels of perceived risk relative to those without a
family history. In addition, an interaction revealed that psychological distress
was greater among men with a family history only among those who also reported
elevated perceived risk. CONCLUSIONS: Similar to other prostate carcinoma
screening programs, men in the current sample largely elected to attend the
screening on their own. Furthermore, although perceived risk was higher among men
with a family history compared with those without a family history, psychological
distress was greater among men with a family history only among those who also
reported elevated perceived risk. Thus, among men with a family history of the
disease, perceived risk may be a marker of elevated psychological distress.
Screening programs should assess family history and perceived risk because of the
potential psychological implications for screening participants.
PMID- 10189137
TI - Short term pretreatment with medroxyprogesterone and testosterone may potentiate
irradiation damage to spermatogenesis in rats.
AB - BACKGROUND: Hormonal treatments lasting 2-6 months inhibit spermatogenesis in men
and have been proposed as germ cell protection against anticancer therapy.
Because it is unthinkable to delay anticancer treatments, the authors
investigated the protection afforded against irradiation of rats by 22 days of
hormonal pretreatment. METHODS: Adult Sprague-Dawley rats were assigned to an
untreated control group (C) or to one of 5 treatments: medroxyprogesterone
acetate plus testosterone only (M), 3 or 5 gray of irradiation (R3 and R5), or
hormonal treatment prior to 3 or 5 gray of irradiation (MR3 and MR5). Mating
trials were conducted 1, 24, 45, 65, 86, and 109 days after treatment. At 122
days, genital organ weights, testis histology, and epididymal spermatozoa were
evaluated. RESULTS: Irradiation reduced sperm production and had a clastogenic
effect on postmeiotic germ cells. No protective effect of steroid treatment was
observed. Moreover, testis weight, tubule diameter, the repopulating index, and
the sperm head count decreased more in the MR5 group than in the R5 group. Mating
tests showed decreases in positive vaginal smears and fertility at both 45 and 65
days, and an increase in resorption at 109 days. CONCLUSIONS: These results
indicate that hormonal pretreatment potentiates irradiation damage to germ cells,
especially stem cells, as regards survival and genomic alterations, probably
because of increased lipoperoxidation of late spermatids.
PMID- 10189139
TI - Resection of small, residual retroperitoneal masses after chemotherapy for
nonseminomatous testicular cancer: a decision analysis.
AB - BACKGROUND: After chemotherapy for metastatic, nonseminomatous testicular cancer,
small, retroperitoneal lymph nodes still harbor mature teratoma or viable cancer
cells in less than half of patients with normal tumor markers. Surgical resection
is an effective treatment to remove residual masses, but observation may also be
considered. METHODS: Using a decision analysis model, the authors estimated the
survival achieved with either resection or observation for patients with residual
masses measuring 0-20 mm. Prognostic estimates were obtained from an
international data set containing 362 patients with masses < or =20 mm and from
10 clinical experts. RESULTS: According to the model, resection prolonged life
expectancy by more than 2 years for masses 11-20 mm and by more than 1 year for
masses 0-10 mm. The estimated gains in 5-year survival were 4.3% and 2.7%,
respectively. In a sensitivity analysis, these results appeared rather robust for
changes in the estimates of the experts. The magnitude of the gain in survival,
however, depended on the probabilities of the residual histologies, which could
be estimated with several well-known predictors, and the assumed benefit of
resection for residual mature teratoma or cancer. CONCLUSIONS: Resection may on
average be beneficial for patients with small, residual masses. The expected
benefit depends on the probability and risks of residual malignancy, regarding
which further research is required. For decision-making regarding individual
patients, the morbidity and costs of resection and a patient's individual
preferences should be considered in addition to any assumed gain in survival.
PMID- 10189138
TI - Expression of vascular endothelial growth factor in patients with testicular germ
cell tumors as an indicator of metastatic disease.
AB - BACKGROUND: Angiogenesis is essential for tumor growth and metastasis. Vascular
endothelial growth factor (VEGF) and thymidine phosphorylase (TP)/platelet
derived endothelial cell growth factor (PD-ECGF) are involved in increased
angiogenic activity and disease progression in solid tumors. However, there is no
information regarding the association of these angiogenic factors with
clinicopathologic findings in testicular germ cell tumors (GCTs). METHODS: The
authors examined the expression of VEGF and TP as well as microvessel density in
GCTs and their association with clinicopathologic findings. Expression of VEGF
and TP and microvessel density were examined immunohistochemically in 80 GCTs,
including 33 seminomas (25 tumors with organ-confined disease and 8 with
metastasis) and 47 nonseminomatous testicular GCTs (NSGCTs) (20 tumors with organ
confined disease and 27 with metastasis). Expression of VEGF also was examined in
four GCTs and one nonneoplastic testis by immunoblotting. RESULTS: VEGF protein
was expressed more highly in GCTs compared with nonneoplastic testes. VEGF
expression in GCTs was correlated significantly with microvessel count (P <
0.001). Both VEGF expression and microvessel count were correlated with
metastasis in seminoma (P = 0.008 and P < 0.001, respectively), but only VEGF
expression was identified as statistically significant by multiple regression
analysis (P = 0.006). Conversely, four variables (VEGF expression, microvessel
count, the presence of venous invasion, and the presence of embryonal carcinoma
elements in the primary tumor) were correlated with metastasis in NSGCT (P <
0.001, P < 0.001, P = 0.004, and P = 0.029, respectively). However, multiple
regression analysis revealed that only VEGF expression and microvessel count were
significant factors for metastasis (P < 0.007 and P < 0.001, respectively). In
contrast, high levels of TP were observed in infiltrating cells, but not in the
majority of cancer cells. CONCLUSIONS: The findings of the current study suggest
that VEGF expression is involved in tumor development, angiogenesis, and
metastasis in GCT.
PMID- 10189140
TI - Unusual clinical presentation of upper urothelial carcinoma in Taiwan.
AB - BACKGROUND: The unusual clinical picture of transitional cell carcinoma (TCC) in
Taiwan appears to be different from that reported elsewhere. METHODS: The authors
reviewed their experience of 135 cases of pathologically proven TCC of the upper
urinary tract. Data regarding the gender ratio and clinical presentation were
analyzed. RESULTS: The male to female ratio was found to be 1 to 1.3, showing a
slight female predominance. The ratio of TCC of the renal pelvis to TCC of the
ureter to TCC of the bladder was noted to be approximately 1.1:0.9:8.0. TCC of
the renal pelvis accounted for 10.7% of all urothelial TCC, and for approximately
40% of all renal carcinomas. CONCLUSIONS: The results of the current study found
that the gender incidence and ratio of renal pelvis TCC to all renal carcinomas
are different in Taiwan compared with data presented in the majority of other
studies.
PMID- 10189141
TI - Unusual features of thyroid carcinomas in Japanese patients with Werner syndrome
and possible genotype-phenotype relations to cell type and race.
AB - BACKGROUND: Werner syndrome (WS), an autosomal recessive disease characterized by
premature aging, has a high frequency of association with six rare neoplasms in
Japanese patients, and only four of these neoplasms also occur excessively in
whites. Several differ from what is usual in their epidemiology and/or histology.
Described in this article are peculiarities in the occurrences of follicular and
papillary thyroid carcinomas among Japanese patients and the possible genotype
phenotype relations pertaining to cell types and the absence of excess thyroid
carcinoma occurrence in whites with WS. METHODS: Epidemiologic features of 23
histologically diagnosed thyroid carcinomas from a series of 150 cancers in 845
Japanese patients with WS were compared with those of 19,446 tumors in a Japanese
national registry of thyroid carcinomas from 1977-1991. Germline mutations had
been determined by molecular studies of peripheral blood. RESULTS: The average
age of patients with thyroid carcinoma was 39 years for those with WS and 49
years for the registry patients. The female-to-male ratios were 2.3:1 and 6.6:1,
respectively. The rates of occurrence of papillary, follicular, and anaplastic
carcinomas were 35%, 48%, and 13% for Japanese patients with WS and 78%, 14%, and
2% in the general Japanese population. All four cases of follicular carcinoma had
germline mutations of the WS gene in the C-terminal region, and the germline
mutation for the only papillary carcinoma was in the N-terminal region.
CONCLUSIONS: This study suggests two possible WS genotype-phenotype relations.
One concerns thyroid carcinoma histology; the other concerns frequent mutations
that occur in the C-terminal region in Japanese patients, but not in white
patients, with WS. These may account for the excess thyroid carcinoma occurrence
among Japanese.
PMID- 10189142
TI - A case-control study of non-Hodgkin lymphoma and exposure to pesticides.
AB - BACKGROUND: The incidence of non-Hodgkin lymphoma (NHL) has increased in most
Western countries during the last few decades. Immunodefective conditions are
established risk factors. In 1981, the authors reported an increased risk for NHL
following exposure to certain pesticides. The current study was designed to
further elucidate the importance of phenoxyacetic acids and other pesticides in
the etiology of NHL. METHODS: A population-based case-control study in northern
and middle Sweden encompassing 442 cases and twice as many controls was
performed. Exposure data were ascertained by comprehensive questionnaires, and
the questionnaires were supplemented by telephone interviews. In total, 404 cases
and 741 controls answered the questionnaire. Univariate and multivariate analyses
were performed with the SAS statistical data program. RESULTS: Increased risk for
NHL was found for subjects exposed to herbicides (odds ratio [OR], 1.6; 95%
confidence interval [CI], 1.0-2.5) and fungicides (OR, 3.7; 95% CI, 1.1-13.0).
Among herbicides, the phenoxyacetic acids dominated (OR, 1.5; 95% CI, 0.9-2.4);
and, when subclassified, one of these, 4-chloro-2-methyl phenoxyacetic acid
(MCPA), turned out to be significantly associated with NHL (OR, 2.7; 95% CI, 1.0
6.9). For several categories of herbicides, it was noted that only exposure
during the most recent decades before diagnosis of NHL was associated with an
increased risk of NHL. Exposure to impregnating agents and insecticides was, at
most, only weakly related to NHL. CONCLUSIONS: Exposure to herbicides in total,
including phenoxyacetic acids, during the decades before NHL diagnosis resulted
in increased risk for NHL. Thus, the risk following exposure was related to the
latency period. Fungicides also increased the risk for NHL when combined, but
this group consisted of several different agents, and few subjects were exposed
to each type of fungicide.
PMID- 10189143
TI - Outcome of advanced stage low grade follicular lymphomas in a population-based
retrospective cohort.
AB - BACKGROUND: To the authors' knowledge previous reports of patient outcome for
advanced stage low grade follicular lymphomas (LGFL) have not been population
based. This is the first report describing the outcome of these patients based on
a population-based cohort. METHODS: A retrospective chart review was performed
for all patients diagnosed with advanced stage LGFL between 1987-1995 for the
adult population of central and northern Alberta, Canada. RESULTS: One hundred
and fifty-seven patients were diagnosed with advanced stage LGFL. Approximately
45% of patients had died at last follow-up. Treatment was initiated at the time
of diagnosis in 87 patients (55%), with alkylating agents used in 66% of them. Of
the 70 patients not treated at the initial diagnosis, 69% had been treated at a
median of 16.3 months. The overall median survival was 5.9 years. On univariate
analysis, significant variables (P < 0.20) included age, B symptoms, symptomatic
lymphadenopathy, symptomatic splenomegaly, splenomegaly, Eastern Cooperative
Oncology Group performance status, baseline lactate dehydrogenase (LDH), diffuse
component on histology, and treatment at the time of diagnosis. By multivariate
analysis, the only factors that influenced survival significantly and
independently were baseline LDH and B symptoms. An elevated baseline LDH had a
hazard ratio of 2.80 (95% confidence interval [CI], 1.65, 4.74) and a median
survival of 8.0 years versus 3.6 years (P < 0.0001). B symptoms had a hazard
ratio of 2.30 (95% CI, 1.23, 4.30) and a median survival of 6.5 years versus 3.1
years (P < 0.0067). CONCLUSIONS: Although some patients with advanced stage LGFL
enjoy a prolonged survival, 80% of deaths in this cohort were attributable to
lymphoma. The median overall survival of 5.9 years offers a less positive
perspective on the outcome of these patients than in previous nonpopulation-based
reports. This emphasizes the need for further population-based studies as well as
new therapeutic approaches, especially those directed toward patients with poor
prognostic features such as elevated baseline LDH and B symptoms.
PMID- 10189144
TI - Incidence of cancer in postmyocardial infarction patients treated with short
acting nifedipine and diltiazem. Secondary Prevention Group.
AB - BACKGROUND: Recent reports suggest a possible link between nifedipine (but not
diltiazem) and an increased risk of cancer in patients being treated with calcium
antagonists. METHODS: A total of 1054 postmyocardial infarction patients were
divided randomly into those being treated with calcium antagonists (n = 566
[nifedipine, 425 patients and diltiazem, 141 patients]) and controls (no calcium
antagonist; n = 488). The patients were followed for 26.3 months, and the
incidences of cardiac events as well as cancer were compared among the 3 groups.
RESULTS: Thirteen patients (2.7%) in the control group developed cancer, whereas
15 patients in the nifedipine group (3.5%; odds ratio, 1.34; 95% confidence
interval [95% CI], 0.63-2.85) and 3 patients in the diltiazem group (2.1%; odds
ratio, 0.89; 95% CI, 0.27-2.93) developed cancer. CONCLUSIONS: Diltiazem appears
to present no increased risk of cancer. The incidence of cancer was slightly
higher in the patients receiving nifedipine than in those not being treated with
a calcium antagonist, which is consistent with earlier reports; however, this
increase was not statistically significant.
PMID- 10189145
TI - The effect of interferon on mouse myocardial capillaries: an ultrastructural
study.
AB - BACKGROUND: Cardiotoxicity, including ischemia and myocardial infarction, is one
of the complications observed after treatment with interferon (IFN). Therefore,
the question has been raised whether IFN may cause damage to the small myocardial
blood vessels. METHODS: In this study, 400 U of IFN-alpha-2b per g of body weight
were injected intraperitoneally into 2 groups of C57 B1 mice, 5 days a week for 3
and 5 months, respectively. Thin sections of the myocardium were examined with a
transmission electron microscope and the ultrastructure of the capillaries was
compared with that of control animals. RESULTS: The results showed a
statistically significant increase in the thickness of the endothelial processes
of the myocardial capillary walls in the mice treated with IFN, with a subsequent
decrease in the size of the capillary lumen. The entire capillary area was not
affected. CONCLUSIONS: These findings may serve as an additional explanation for
the cardiac complications observed in patients treated with IFN.
PMID- 10189146
TI - Parental cigarette smoking and the risk of acute leukemia in children.
AB - BACKGROUND: Studies of the relation between parental smoking and childhood
leukemia have produced inconsistent results. In the largest case-control studies
of childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML)
conducted to date, the authors evaluated leukemia risk relative to parental self
report of cigarette smoking. METHODS: In telephone interviews in which a
structured questionnaire was used, parents of 1842 ALL patients, 517 AML
patients, and their matched controls were asked about their cigarette smoking
habits before, during, and after the pregnancy with the index child. Risk of
leukemia was examined by histologic type, age of the child at diagnosis,
immunophenotype (for ALL), and French-American-British morphology group (for
AML). RESULTS: The risk of ALL was not associated with the father's ever having
smoked (odds ratio [OR] = 1.04, 95% confidence interval [CI] 0.90-1.20) or the
mother's ever having smoked (OR = 1.04, 95% CI 0.91-1.19). Similarly, no
significant risk of AML was observed for paternal (OR = 0.88, 95% CI 0.67-1.16)
or maternal smoking (OR = 0.95, 95% CI 0.74-1.22). The relative risk of leukemia
was not significantly different from the null for parental smoking in any time
period during or around the index pregnancy, nor was it related to the number of
cigarettes, the number of years of smoking, or the number of pack-years. A small
number of sporadic, statistically significant associations were found, but
overall there appeared to be no association between parental cigarette smoking
and ALL or AML, or any subgroup of leukemia. CONCLUSIONS: Parental smoking while
pregnant or exposure to cigarette smoke shortly after birth is unlikely to
contribute substantially to the risk of childhood leukemia in North America.
PMID- 10189147
TI - Genomic imprinting of H19 and insulin-like growth factor-2 in pediatric germ cell
tumors.
AB - BACKGROUND: Insulin-like growth factor-2 (IGF2) and H19 are reciprocally
imprinted genes on chromosome 11; IGF2 is expressed paternally and H19 is
expressed maternally. Loss of imprinting (LOI) at both H19 and IGF2 has been
reported in seven fully informative adult testicular germ cell tumors (GCTs) and
may contribute to germ cell carcinogenesis. METHODS: Genomic DNA from 61
pediatric GCTs was amplified by polymerase chain reaction (PCR) and screened for
heterozygosity at both IGF2 and H19 using either ApaI or RsaI, respectively. If
heterozygous, polyadenylated RNA was isolated and reversed-transcribed into cDNA.
cDNA then was amplified by PCR and the products were digested with restriction
enzymes to evaluate GCT expression of IGF2 and H19. RESULTS: Eleven pediatric
GCTs were fully informative for H19 and IGF2, including 5 ovarian GCTs, 2
testicular GCTs, and 4 extragonadal GCTs. Consistent with prior studies, both
testicular GCTs showed LOI at both H19 and IGF2. In contrast, three of the five
ovarian GCTs had LOI at both IGF2 and H19; one had LOI at IGF2 only, and one
retained imprinting at both loci. Only one of the four extragonadal GCTs had LOI
at IGF2 whereas three of the four had LOI at H19. CONCLUSIONS: These data suggest
that LOI at H19 and IGF2 also may be common in pediatric testicular GCTs.
However, ovarian and extragonadal pediatric GCTs showed variable patterns of LOI
that may indicate differences in the timing of carcinogenesis in germ cells at
these sites.
PMID- 10189148
TI - Induction failure in acute lymphoblastic leukemia of childhood.
AB - BACKGROUND: Although it is widely accepted that failure to achieve complete
remission (CR) portends a poor prognosis in childhood acute lymphoblastic
leukemia (ALL), there is variability in the precise definition of induction
failure and, to the authors' knowledge, few published data exist regarding the
outcome of patients who are slow to achieve CR. METHODS: Between 1987-1995, 774
children with ALL were treated on 2 consecutive protocols and were evaluable to
assess the time required to attain CR. The authors compared presenting
characteristics and outcomes of patients based on their remission status after 1
month of induction chemotherapy: CR (n = 656), protracted hypoplasia (low
peripheral blood counts and/or hypocellular marrow) (n = 95), and persistent
leukemia (M2 or M3 bone marrow and/or evidence of extramedullary leukemia) (n =
23). The median follow-up was 5.2 years. RESULTS: Presenting features that
predicted persistent leukemia included a leukocyte count > 100,000/mm3 and T-cell
phenotype. Approximately 91% of patients with persistent leukemia and 100% with
protracted hypoplasia eventually achieved CR. The 5-year event free survival
(EFS) (95% confidence intervals [95% CI] in parentheses) for patients with
persistent leukemia after 1 month was 16% (95% CI, 0%, 31%), which was
significantly worse (P < 0.001) than that for those who achieved CR within 1
month (5-year EFS, 82%; 95% CI, 79%, 86%) and that for those with protracted
hypoplasia (5-year EFS, 79%; 95% CI, 70%, 87%). For patients with persistent
leukemia, there was no significant difference in survival based on bone marrow
status (M2 or M3) after 1 month or on the number of induction cycles received
before achieving CR. CONCLUSIONS: Patients with persistent leukemia at the end of
1 month of therapy have a dismal prognosis, regardless of when they subsequently
achieve CR. More intensive and/or novel therapies should be considered for this
subset of patients.
PMID- 10189149
TI - Frequently asked questions regarding the application of the TNM classification.
TNM/Prognostic Factors Project (International Union Against Cancer [UICC]).
PMID- 10189150
TI - The vibroacoustic disease--an emerging pathology.
AB - Vibroacoustic disease (VAD) is the clinical manifestation of a systemic disease
that develops after long-term exposure to noise (> or = 10 yr) which is
characterized by large pressure amplitude (> or = 90 dB SPL) within the lower
frequency bands (< or = 500 Hz). Noisy environments produce more widespread
systemic effects than initially suspected. This paper describes the chronology,
population studied, and the statistical treatment used in our studies of VAD over
the past 20 yr. We also describe the motivation that led to the evaluation and
assessment of the exposed employees. Future research aims are also discussed.
PMID- 10189151
TI - Noise-induced extra-aural pathology: a review and commentary.
AB - The focus of this review paper will be the effects of acoustic phenomenon
(noise), characterized by large pressure amplitude (> or =90 dB) and low
frequency (< or =500 Hz) (LPALF) on humans and animal models. Current concepts
imply the assumption that such LPALF noise impinges only on, or through, the
somatic medium of the auditory system. As a consequence of this assumption, the
effect of noise on humans is only regulated for purposes of hearing conservation.
Guidelines and regulations governing occupational noise assessments are biased
toward the subjective human perception of sound. The author will not make the
assumption that airborne acoustic phenomena impacts only on the auditory system,
and will present a literature review providing evidence for such position. The
purpose of this review paper is to defend the existence of extra-aural, noise
induced pathology, particularly the vibroacoustic disease; and to advance the
recognition that the respiratory tract could very well be a target organ of this
environmental stressor.
PMID- 10189152
TI - Noise assessment during aircraft run-up procedures.
AB - BACKGROUND: A comprehensive noise survey was conducted at Oficinas Gerais de
Material Aeronautico (OGMA), Alverca, Portugal, and at several Portuguese Air
Force (PoAF) bases, as part of an ongoing occupational noise assessment program.
The major objectives consisted of measuring and analyzing noise radiated by
various types of military aircraft while undergoing maintenance, repair, or
testing. METHODS: Amplitude, frequency, time history and statistical analysis
were conducted on noise emitted by aircraft during run-up procedures. Analysis
and evaluation used various noise indexes (Leq and Lmax), frequency spectra, and
sound pressure time histories for the assessment of noise exposure on the
employees during their working life span. RESULTS: The results show a
predominance of large pressure amplitudes within the lower frequency bands. This
was correlated with long-term clinical observations in these workers. This study
corroborates the definition of vibroacoustic disease as a systemic, noise-induced
occupational pathology caused by long-term (>10 yr) exposure to large pressure
amplitude (> or = 90 dB SPL) and low frequency (< or = 500 Hz) noise.
PMID- 10189153
TI - A unique case of vibroacoustic disease: a tribute to an extraordinary patient.
AB - This paper describes the case of a patient, Mr. A, who died in 1987. The
information provided by Mr. A in life, and his insistence on making a will
demanding an autopsy on his death, has given us invaluable data on Vibroacoustic
Disease (VAD). Mr. A was an intellectually curious man who researched the medical
literature related to his condition, and compared it to his own experience. He
would describe all his sensations during his many epileptic seizures. Solely
because of the results of Mr. A's autopsy, new avenues of research were
initiated. These have led to new concepts and exciting new perspectives on noise
induced extraaural pathology. VAD is today a well-established and easily
diagnosed entity. This paper is a tribute to Mr. A, in whose honor we have an on
going commitment to establish VAD as an occupational disease, reimbursable by
Worker's Compensation.
PMID- 10189154
TI - The clinical stages of vibroacoustic disease.
AB - BACKGROUND: Vibroacoustic disease (VAD) is an occupational disease occurring in
susceptible workers who have had long-term exposure (> or = 10 yr) to large
pressure amplitude (> or =90 dB SPL) and low frequency noise (< or = 500 Hz). The
clinical progression is insidious, and lesions are found in many systems
throughout the body. Some of the findings, such as extracellular matrix changes,
appear to be specific to this disease. Others, such as cognitive impairment, seem
to be common in different types of stress-induced pathology. In 1956, Professor
Eugenia Andreeva-Galanina developed a classification of hand-arm vibration
induced pathology. This has been further refined and has become an important tool
in occupational medicine. Thus, it is also important now to define the clinical
stages of VAD in accordance with the appearance of the most common signs and
symptoms. METHODS: We analyzed the files of 140 patients with VAD, paying close
attention to the chronology of the clinical findings, the registry of eventual
and on-the-job accidents, and the evaluation of disabilities. RESULTS: We have
classified VAD in function of the time it took for 50% of the population to
acquire the relevant sign or symptom. Stage I, mild signs (behavioral and mood
associated with repeated infections of the respiratory tract, e.g., bronchitis);
Stage II, moderate signs (depression and aggressiveness, pericardial thickening
and other extracellular matrix changes, light to moderate hearing impairment, and
discrete neurovascular disorders); Stage III, severe signs (myocardial
infarction, stroke, malignancy, epilepsy, and suicide). CONCLUSION: This
classification should be capable of assessing work fitness, and is a primary
approach to a complex and multidisciplinary problem with implications in
diagnosis, prevention and disability compensation within VAD.
PMID- 10189155
TI - Sister chromatid exchange analysis in workers exposed to noise and vibration.
AB - BACKGROUND: There has been a growing interest in the combined effects of noise
and vibration. In a population of aeronautical workers diagnosed with
vibroacoustic disease (VAD), a large incidence of malignancy was detected. These
workers were exposed to large pressure amplitude (LPA) (> or = 90 dB SPL) noise,
with energy content concentrated within the low frequency (LF) bands (< or = 500
Hz) and whole-body vibration (WBV). To our knowledge, there are no studies
conducted in humans or animals that address the issue of the potential genotoxic
effects of vibration combined with noise. In the present study, the levels of
sister chromatid exchanges (SCE) and of cells with high frequencies of SCE (HFC)
were analyzed in peripheral blood lymphocytes of workers employed in various
occupations within the aeronautical industry. METHODS: SCE and HFC were analyzed
in lymphocytes of 50 workers occupationally exposed to noise and vibration and of
34 office-worker controls (G0). The exposed group included: 10 hand-vibrating
tool operators (G1), 15 engine test cell technicians (G2), 12 aircraft run-up
technicians (G3) and 13 Portuguese Air Force helicopter pilots (G4). Groups 2-4
were exposed to WBV and LPALF noise; group 1 was exposed to LPA high frequency
noise and local vibration. Statistical analysis of the mean SCE count per cell
was carried out by multiple regression analysis comparing various predictor
variables: type of exposure, duration of exposure, age, and cigarette
consumption. RESULTS: Only cigarette consumption and type of exposure were found
to be significantly correlated with the mean SCE frequency. After allowing for
the effects of smoking, the analysis indicates that: 1) there was no significant
difference between G1 and G0 (p > 0.05); 2) the differences between G2 and G0, G3
and G0, G4 and G0 were all highly significant (p < 0.001); 3) there was no
significant difference between G2 and G3 (p > 0.05), nor between G2 and G3
combined and G4 (p > 0.05); and 4) G2 and G4 combined had a significantly
elevated mean SCE frequency compared G0 (p < 0.001). Statistical analysis of the
proportion of HFC was consistent with these results. CONCLUSION: Our data suggest
that occupational exposure to LPALF noise and WBV may lead to increased levels of
SCE in men. These results also suggest a reason for the high incidence of
malignancy in VAD patients. The observed effects may not reflect a direct action
of these physical agents on DNA. Alternative explanations may lie in the noise-,
vibration-, and/or stress-induced pathophysiological changes.
PMID- 10189156
TI - Echocardiographic evaluation in 485 aeronautical workers exposed to different
noise environments.
AB - INTRODUCTION: Vibroacoustic disease (VAD) is a heterogeneous and systemic entity,
caused by long term (> or =10 yr) exposure to noise environments characterized by
large pressure amplitude and low frequency (LPALF) (> or =90 dB SPL, < or = 500
Hz), and not explained by other possible etiologic agents. The goal of this study
was to identify possible structural changes in hearts of men with suspected VAD.
METHODS: A total of 485 men were divided into 3 noise groups: no noise exposure
(< or =70 dB), n = 48 (Group I); moderate noise exposure, (>70dB and < 90 dB), n
= 113 (Group II); and intense noise exposure (> or =90 dB), n = 324 (Group III).
Echo-Doppler studies were performed (HP SONOS 1500) and recorded on coded
videotapes. Three observers performed blinded evaluations of 26 echo-Doppler
parameters. For the purpose of the present study only 12 morphological parameters
were compared among the groups: thickening of the mitral, aortic, tricuspid, and
pulmonary valves, pericardium and endocardium; mitral valve regurgitation,
prolapse and ruptured chordae tendinae; and inflow velocities. Thickness and
severity of the applicable parameters were scored in seven-grade scale (0,0.5,1,
...,3). RESULTS: All evaluated parameters were statistically significantly
different in Group I vs. Group III, except flow velocity E. Comparison of Group I
vs. Group II revealed statistically significant differences in mitral, aortic,
tricuspid and pericardial thickening, with the strongest evidence for mitral and
pericardial structures. CONCLUSIONS: This confirms the results of previous
studies. Occupational exposure to noise environments characterized by LPALF noise
causes structural changes in the heart. Mitral valve and pericardial thickening
constitute the first signs of VAD.
PMID- 10189157
TI - The human pericardium in vibroacoustic disease.
AB - INTRODUCTION: One of the main features of vibroacoustic disease (VAD) is the
proliferation of the extra-cellular matrix which induces cardiovascular
morphological and dynamic changes, and has been evaluated through echo-Doppler.
While all subjects exposed to large pressure amplitude (> or =90 dB SPL) and low
frequency (< or =500 Hz) (LPALF) for at least 15 yr have thickening of some
cardiac structure, most frequently the pericardium, no significant diastolic
changes accompany these observations. Echocardiography has become the diagnostic
method of choice for the VAD. However, there have been no studies relating the
echo-images of pericardial thickening to gross anatomy. METHODS: We present the
histology and ultrastructure of the pericardia of four patients who underwent
cardiac surgery. RESULTS: The most important findings concern the real thickening
of the pericardium (values: 1.11, 1.35, 2.19, and 2.33 mm vs. norm: < or = 0.5
mm), the dynamic arrangements of mesothelial cells in the serosa layer, and the
plasticity of the cells found among the multifascicular waveform collagen fibers.
We found that the fibrosa of VAD patients has three layers: sandwiched between
two thickened layers of normal fibrosa there is a loose tissue layer with
vascular, nervous, and adipose structures. CONCLUSION: These features may
partially explain why no important diastolic changes are observed in VAD patients
in spite of the pericardium thickening.
PMID- 10189158
TI - Airway flow limitation in patients with vibroacoustic disease.
AB - INTRODUCTION: Vibroacoustic disease (VAD) is a pathology caused by occupational
exposure to large pressure amplitude and low frequency (LPALF) noise (> or =90 dB
SPL, < or =500 Hz), and has been the object of study by this group for the past
20 yr. In a group of 140 VAD-diagnosed patients, 7 non-smoker aircraft
technicians developed clinical signs of respiratory insufficiency at an early
age. Previously, multi-focal fibrosis had been observed in the lung of Wistar
rats exposed to occupationally simulated LPALF noise and with no possibility of
contamination by fumes, dust or other chemical agents. The goal of this study is
to compare pulmonary imaging and/or functional changes in two age- and exposure
time matched groups of VAD-diagnosed aircraft technicians, with and without
airflow limitation symptoms. METHODS: In a population of 140 individuals
occupationally exposed to LPALF noise and diagnosed with VAD, we excluded the
smokers (45 cases) and selected 7 individuals with complaints of airway flow
limitations, average age 42.3 yr (SD = 2.3). From the remaining non-smokers
without respiratory complaints, we selected a group of 15, age-matched patients
(average age 36 yr, SD = 6.5). All subjects received a high-resolution CT scan of
the chest and respiratory function tests consisting of body plethysmography,
spirometry and metacholine airway provocation. RESULTS: There is a significant
relationship between the presence of symptoms and imaging of lung fibrosis
through high-resolution CT scan (p = 0.03624). There are no significant
differences when both groups are compared with respect to the percentage of
predicted values of lung function: Vital Capacity (VC), Total Lung Capacity,
Forced Expiratory Volume during the first second of expiration, Maximal
Expiratory Flow at 50% VC, Total Airway Resistance, and Airway Reactivity after
25 mg of metacholine. CONCLUSION: High resolution CT scan is a valuable tool for
diagnosis of lung fibrosis in VAD patients who have symptoms of airway flow
limitations. The fact that lung ventilation tests did not present significant
changes between both groups is in agreement with findings in Wistar rats. This
strongly suggests that a process of focal pulmonary fibrosis may be induced by
occupational noise exposure, and is a feature of VAD.
PMID- 10189159
TI - Morphological changes in rat lung parenchyma exposed to low frequency noise.
AB - BACKGROUND: Airway flow limitation is has been identified in nonsmoker
aeronautical technicians who are exposed to long term (> or =10 yr) large
pressure amplitude and low frequency (LPALF) noise (> or =90 dB, < or =500 Hz).
Considering this work environment, some kind of pulmonary impairment would be
expected, given the probable, but not de facto, existence of fuel exhausts and
vapors. In the course of morphofunctional studies of rat pleura exposed to LPALF
noise environments, intense subpleural fibrosis was identified. Thus, we decided
to study the deep lung parenchyma of these noise-exposed rodents. METHODS: One
group of five Wistar rats was exposed to LPALF noise for a cumulative 4000 h, and
another of five rats were exposed for a cumulative of 5000 h. The control group
consisted of 10, age-matched, Wistar rats that were kept in the same conditions,
but in silence. Fragments of lung parenchyma were extracted after sacrifice, and
processed for light microscopy, and for scanning and transmission electron
microscopy. RESULTS: Focal interstitial fibrosis of the deep lung parenchyma were
identified as well as changes in the small bronchial cilia. The amount of brush
cells was increased in the locations where microvilli were abnormal. An obvious
increase of alveolar type II pneumocyte cells was observed with numerous, large
and confluent lamellar bodies. DISCUSSION: In contrast with the normal lung
morphology observed in the control group, changes in the extra-cellular matrix
and epithelial cells were identified in the exposed rats. No fuel exhaust, vapors
or dust were present in the environment of the noise-exposed rats. These results,
linked with the respiratory disorders identified in noise-exposed humans,
strongly suggest that LPALF noise is an agent of pulmonary fibrosis.
PMID- 10189160
TI - Morphofunctional study of rat pleural mesothelial cells exposed to low frequency
noise.
AB - BACKGROUND: Vibroacoustic disease (VAD) is a noise-induced pathology occurring in
workers occupationally exposed to large pressure amplitude (> or =90 dB SPL) and
low frequency (< or = 500 Hz) (LPALF) noise, over long periods of time (> or = 10
yr). Patient complaints frequently involve the respiratory tract. There have been
three cases of pleural effusion of unknown etiology and with unusually long
recovery times. To better understand what may be occurring we studied the effects
of LPALF noise on the morphological and functional characteristics of pleural
mesothelial cells of Wistar rats. METHODS: The animals were exposed to LPALF
noise for periods ranging from 24-600 h. An intrapleural instillation of calcium
tungstate was performed, and after sacrifice the pleural visceral and parietal
leaflets were studied by scanning electron microscopy. RESULTS: Acute exposure to
LPALF noise caused a temporary decrease in the number of mesothelial microvilli,
and prolonged exposure resulted in a definite decrease in their number as well as
an impairment of their capacity to absorb particles within in the pleural space.
CONCLUSION: These results explain the pleural pathology found in human patients
with VAD and confirm the deleterious effect of LPALF noise on the respiratory
system.
PMID- 10189161
TI - The effect of chronic exposure to low frequency noise on rat tracheal epithelia.
AB - INTRODUCTION: Vibroacoustic Disease (VAD) is a multi-systemic entity caused by
occupational or chronic exposure to large pressure amplitude and low frequency
(LPALF) noise (> or = 90 dB SPL, < or = 500 Hz). The clinical picture involves
extra-auditory pathology, such as neurological disturbances, respiratory
disorders and cardiovascular problems. Among the first complaints of VAD patients
are coughing, bronchitis, and inflammation or infection of the oral cavity and
the upper respiratory pathways. The goal of ths study was to investigate the
effects of occupationally simulated LPALF noise exposure on rat tracheal
epithelium to determine if they could explain the symptoms found in VAD patients.
METHODS: We exposed 20 Wistar rats to occupationally simulated (8 h x d(-1), 5d x
wk(-1)) LPALF noise for an accumulated total of 1236 h. The control group
consisted of 10 age-matched rats, kept in equal conditions but in silence.
Histological and ultrastructural studies were performed on the tracheal epithelia
of both populations. RESULTS: The most dramatic changes were identified in the
ciliated cells of the exposed rats. There were frequent images of shaggy or
necrotic cilia as well as regularly to partially sheared cilia. Also, there were
frequent images of different stages of cilia recovery. CONCLUSION: Occupationally
simulated exposure to LPALF noise can cause important changes in ciliated cells
rat tracheal epithelia. This may partially explain the clinical findings observed
in VAD patients.
PMID- 10189162
TI - Neurological aspects of vibroacoustic disease.
AB - INTRODUCTION: Mood and behavioral abnormalities are the most common early
findings related to vibroacoustic disease (VAD). Other signs and symptoms have
been observed in VAD patients. Brain MRI discloses small multifocal lesions in
about 50% of subjects with more than 10 yr of occupational exposure to large
pressure amplitude (> or = 90 dB SPL) and low frequency (< or = 500 Hz) (LPALF)
noise. However, to date, there have been no studies globally integrating all the
neurological, imaging and neurophysiological data of VAD patients. This is the
main goal of this study. METHODS: The 60 male Caucasians diagnosed with VAD were
neurologically evaluated in extreme detail in order to systematically identify
the most common and significant neurological disturbances in VAD. RESULTS: This
population demonstrates cognitive changes (identified through psychological and
neurophysiological studies (ERP P300)), vertigo and auditory changes, visual
impairment, epilepsy, and cerebrovascular diseases. Neurological examination
reveals pathological signs and reflexes, most commonly the palmo-mental reflex.
CONCLUSIONS: A vascular pattern underlying the multifocal hyperintensities in T2
MR imaging, with predominant involvement of the small arteries of the white
matter, is probably the visible organic substratum of the neurological picture.
However, other pathophyisological mechanisms are involved in epileptic
symptomatology.
PMID- 10189163
TI - Balance disturbances in individuals with vibroacoustic disease.
AB - INTRODUCTION: In previous studies, patients with vibroacoustic disease (VAD)
presented hyperintense foci in T2 of the cerebral white matter, brainstem and
basal nuclei. The most probable etiology is ischemia. One of the most frequent
complaints of these patients is balance disturbances which, in two cases, has
threatened the patients' ability to maintain their jobs. The purpose of this
study was to compare two methods, one neurophysiological (auditory evoked
potentials - AEP) and the other structural imaging (brain MRI), in order to
determine to what extent the changes detected with these methods may be related
to each other in this pathology. METHODS: Twenty individuals occupationally
exposed to large pressure amplitude (> or = 90 dB SPL) and low frequency (< or =
500 Hz) noise, received neurological and otorhinolaryngological examinations. All
of them had previously received audiograms, tympanograms and
electronystagmograms. All 20 patients also received brain MRI and AEP studies.
RESULTS: The individuals with vertigo and changes of the AEP present the greater
number of changes in the brain MRI. CONCLUSION: This could be an indication that
in many VAD cases vertigo may have a central origin.
PMID- 10189164
TI - The palmo-mental reflex in vibroacoustic disease.
AB - BACKGROUND: Vibroacoustic disease (VAD), is a multisystemic nosological entity,
caused by occupational exposure to large pressure amplitude (> or = 90 dB SPL)
and low frequency (< or = 500 Hz) (LPALF) noise. The most common neurological
finding in patients with VAD is the palmomental reflex (PMR). The aim of this
study is to evaluate the frequency and characteristics of this primitive reflex
in a population of VAD patients. METHODS: Sixty individuals, occupationally
exposed to LPALF noise underwent a neurological examination. In each one,
unilateral contraction of the chin muscles was triggered through the stimulation
of the thenar eminence. When a response habituation was observed, or when there
was no response except previously existing skin retraction and small dimples, an
EMG was performed. All these subjects also received brain MRI and measurement of
endogenous evoked potentials. RESULTS: Thirty individuals presented unilateral or
bilateral PMR; 26 of these presented changes in the brain MRI. EMG measurement
evidenced continuous contraction of the chin muscles, without visible PMR,
triggered by the stimulation of the thenar eminence. CONCLUSION: PMR is present
in 50% of the patients with VAD. In the VAD patients, the frequency of abnormal
chin muscle activity is higher than the frequency of PMR and represents a loss of
the cortical control over the brainstem structures.
PMID- 10189165
TI - ERP P300 and brain magnetic resonance imaging in patients with vibroacoustic
disease.
AB - INTRODUCTION: Subjects occupationally exposed to large pressure amplitude (> or =
90 dB SPL) and low frequency (< or = 500 Hz) (LPALF) noise for long term periods
(>10 yr) can develop vibroacoustic disease (VAD). One of the earliest complaints
of VAD patients deals with memory and attention disturbances. On the other hand,
in over 50% of these patients, magnetic resonance imaging (MRI) of the CNS
revealed cortical atrophy and dilation of the perivascular spaces, and small
hyperintense lesions in T2 of the cerebral white matter, basal ganglia, and
brainstem. The purpose of this study is to investigate whether there is any
relationship between these morphological changes and the event-related potentials
(ERP) P300 parameters. METHODS: Sixty aeronautical workers with more than 10 yr
of LPALF noise exposure were studied using brain MRI and ERP P300. A careful
neurological examination had been previously performed on all of them. RESULTS:
The neurological examination revealed abnormalities in 80%, the most common
finding being the archaic palmo-mental reflex. Some 37 subjects had hyperintense
foci in T2 of the subcortical and periventricular white matter, the basal ganglia
and the brainstem. Comparing the ERP P300 amplitude and latency values,
morphology and topography, obtained in these 37 subjects with the data from the
23 who did not have any morphological changes in CNS, we found a strong
correlation between the brain MRI lesions and the neurophysiological changes (p <
0.01). CONCLUSIONS: These results are important for understanding the
pathophysiology of the cognitive impairment found in VAD patients.
PMID- 10189166
TI - Effects of occupational exposure to low frequency noise on cognition.
AB - INTRODUCTION: Previous studies performed on groups of workers employed in the
aeronautical industry revealed morphological vascular changes of the central
nervous system (CNS) and some difficulty in attention and memory retention. The
goal of this study is, therefore, to determine whether prolonged occupational
exposure to large pressure amplitude (> or = 90 dB SPL) and low frequency (< or =
500 Hz) (LPALF) noise leads to cognitive deterioration. METHODS: We observed 40
male workers employed as aircraft technicians, with average age of 43.3 yr (range
35-56, SD = 4.82) occupationally exposed to LPALF noise for a long period of
time, average 22 yr (range 13-30, SD = 4.90), and 30 educationally- and age
matched male controls. None of the subjects had a history of alcoholism, and all
were drug-free. The P300 event-related brain potential elicited with an auditory
discrimination task was recorded and psychological tests (the Wechsler memory
scale and the Toulouse-Pieron test) were performed. RESULTS: The P300 latency was
significantly longer (328.5 vs. 307.5 ms, F = 11.7, deg. signif.=0.001) and the
amplitude significantly smaller (10.9 vs. 12.6, F = 4.3, deg. signif.=0.04) in
the exposed group than in the controls. No significant differences were found in
the results of the Toulouse-Pieron test. The different subscales of the Wechsler
memory scale did not show any significant difference except in the immediate
verbal memory, where the exposed workers were found to have poorer results than
the controls (10.0 vs. 11.3, F = 5.6, deg. signif.=0.02). However, the memory
quotient obtained from the Wechsler memory scale indicated a significant
difference between both groups (101.8 vs. 108.3, F = 10.1, deg. signif.=0.002);
exposed subjects presented lower results. CONCLUSION: These findings suggest that
prolonged exposure to LPALF noise might contribute to cognitive impairment and
that the P300 event-related brain potential recording may be a valuable
diagnostic tool.
PMID- 10189167
TI - Facial dyskinesia induced by auditory stimulation: a report of four cases.
AB - INTRODUCTION: The Vibroacoustic Disease (VAD) is an occupational pathology
induced by long-term (>10 yr) exposure to large pressure amplitude (> or = 90 dB
SPL) and low frequency (< or = 500 Hz) noise. During studies contributing to the
characterization of VAD, abnormal facial movements induced by repetitive auditory
stimuli were observed in one individual employed as an aeronautical mechanic. The
goal of this study was to investigate the existence of movement disorders
triggered by auditory stimuli in a group of VAD-diagnosed patients. METHODS:
Sixty VAD patients received auditory and median nerve stimulation.
Simultaneously, EEG monitoring was performed. RESULTS: Abnormal myoclonus
movements were triggered by auditory stimuli in four patients. EEG recordings
were normal in all 60 patients. Stimulation of the median nerves did not trigger
any abnormal movements. CONCLUSION: These data suggest that this facial
dyskinesia has a subcortical origin.
PMID- 10189168
TI - Epilepsy in the vibroacoustic disease: a case report.
AB - INTRODUCTION: Late-onset epilepsy was one of the first neurological problems
identified in patients diagnosed with vibroacoustic disease. Other clinical
situations, such as automatisms and rage-like reaction crises were also observed.
Some cases of epileptic seizures were triggered by different types of stimuli.
CASE REPORT: This study describes the clinical case of a 30-yr-old male metal
worker who had epileptic seizures when he used vibratory tools common to his
profession, such as drills and sanders. We performed a 21-channel EEG during a
seizure induced in the laboratory by direct contact of a vibratory tool with his
right hand. This allowed us to view the electrical discharge of his left
hemisphere. The entire procedure was simultaneously videotaped while a partial
motor crisis was observed. Brain MRI of this subject revealed multiple
hyperintense focal lesions in the sub-cortical white matter. Echocardiography
revealed thickening of the pericardium and valve structures. COMMENTARY: To the
authors' knowledge, this is the first documented case of reflex epilepsy due to
vibratory stimuli. We briefly discuss the possible pathophysiological mechanisms
of this clinical event.
PMID- 10189169
TI - Effect low frequency noise exposure on BALB/c mice splenic lymphocytes.
AB - INTRODUCTION: Vibroacoustic disease (VAD) occurs in workers exposed for more 10
yr to large pressure amplitude and low frequency (LPALF) noise (> or = 90dB, < or
= 500 Hz). In its initial stages (2 yr exposure), VAD is associated with an
increase in infections of the respiratory tract. The purpose of this study is to
investigate whether exposure of mice to LPALF noise leads to immunological
changes as expressed by the number of different lymphocyte subpopulations in the
animals' spleen. METHODS: Flow cytometry analysis of spleen lymphocytes was
performed in BALB/c mice that had been exposed to occupationally simulated LPALF
noise (8 h x d(-1), 5 d x wk(-1)) for a total of 1272 h (approximately 8 mo). The
following surface phenotypes of splenic lymphocytes were quantified: IgM, CD4,
CD8. Quantification of splenic lymphocytes from non-exposed, age-matched, control
BALB/c mice was also performed. RESULTS: Noise-exposed BALB/c mice had decreased
T cells, involving both helper (CD4+) and cytotoxic (CD8+) lymphocytes, and also
of IgM+ B lymphocytes. CONCLUSION: The data indicate that relatively short term
exposure (3 mo) to LPALF noise induces a decrease in spleen lymphocytes in mice
which is particularly significant (p < 0.003) in CD8+ T lymphocytes. The data
suggest that exposure to LPALF noise causes changes in the immune system of mice.
This is in agreement with previous human studies where VAD patients presented an
enhancement in the number of circulating CD8+ lymphocytes.
PMID- 10189171
TI - Effects of low frequency noise upon the reaction of pleural milky spots to
mycobacterial infection.
AB - INTRODUCTION: Milky Spots (m.s.), also known as Kampmeier's foci, are confined to
the parietal leaflet and act as a barrier to mediastinum infections, having very
important phagocytic functions. Previous studies have made clear that large
pressure amplitude and low frequency (LPALF) noise (> or = 90 dB, < or = 500 Hz)
induces morphofunctional changes on the pleural mesothelium. The purpose of this
study was to investigate the dynamics of m.s., namely the response to infectious
agents reaching the pleural space under noise stress. METHODS: Wistar rats (n =
20) were used; 5 as control and sham operated, 5 exposed to infection but not to
noise, 5 exposed to 1696 cumulative hours of LPALF noise, and 5 exposed to 2184
cumulative hours. Following noise exposures, all rats except the 5 controls were
injected with 0.2 ml of saline solution containing 2 x 10(8) viable mycobacterium
avium bacilli (ATCC-25291 strain, sereotype 2). The rats were sacrificed 21 d
after infection and sections of the retrocardiac pleural leaflets were observed
with a light microscope using the Ziehl-Neelsen staining method. RESULTS: There
was an increase in the number and diameter of the m.s. due to hypercellularity,
mainly caused by the increase of mononuclear cells, and there was formation of
large granulomas containing many mycobacteria. Rats submitted to noise also
presented alterations of the standard morphological changes, namely partial
necrosis of the m.s. CONCLUSION: The data suggest that exposure to LPALF noise
can interfere with the normal immune response to bacterial infection in rats.
This can be an important contribution to the understanding of the disorders in
the pleural space of vibroacoustic disease patients.
PMID- 10189170
TI - Acceleration of lupus erythematosus-like processes by low frequency noise in the
hybrid NZB/W mouse model.
AB - INTRODUCTION: We investigated the effect of low frequency noise on the natural
history of autoimmune diseases using hybrid New Zealand Black (NZB) and White
(NZW) male mice that are prone to spontaneously develop systemic lupus
erythematosus after 6 mo of age. METHODS: We exposed 3-mo-old mice to periods of
low frequency noise (> or = 90 dB SPL, < or = 500 Hz) for a total of 216 h; the
animals were studied up to 12 mo of age and data were compared with results
obtained with age-matched controls. RESULTS: We found that noise exposure caused
an earlier expression of proteinuria, a change that was associated with
acceleration of kidney lesions and increased mortality. At 8 mo of age, after 3
mo of chronic exposure to noise, the exposed mice presented significantly higher
numbers of splenic IgM+ lymphocytes and CD8+ T cells than the age-matched
controls. CONCLUSION: Exposure of lupus-prone mice to low frequency noise
accelerates the expression of the autoimmune disease and it affects the immune
system by raising the number of splenic IgM+ B lymphocytes and CD8+ T cells.
PMID- 10189172
TI - Increase in CD8+ and CD4+ T lymphocytes in patients with vibroacoustic disease.
AB - INTRODUCTION: Some workers employed by the aviation industry are exposed to large
pressure amplitude and low frequency (LPALF) noise (> or =90 dB SPL, < or = 500
Hz) and have developed vibroacoustic disease (VAD), a whole-body noise-induced
pathology. Since VAD patients have an increased prevalence of respiratory and
skin infections, we investigated whether these individuals had any quantitative
changes in the number of peripheral blood cell populations. Also, we investigated
whether different types of noise environments are related to cell quantification.
METHODS: Quantification of peripheral blood cell populations was performed in
venous blood samples of 34 VAD-diagnosed patients, and 41 controls. Leukocytes,
monocytes, granulocytes, and surface phenotypes of CD8+ and CD4+ T lymphocytes
were considered. RESULTS: We found that VAD patients showed a statistically
significant elevation in the number of circulating CD8+ and CD4+ T lymphocytes
when compared with the control population, but not when compared among different
noise-environments. Monocyte and granulocyte populations did not register
significant differences. CONCLUSION: VAD patients present enhancement in the
number of circulating cytotoxic T lymphocytes (CD8+ and CD4+ T cells) thus
indicating that this environmental disease is associated with quantitative
changes in immune cells.
PMID- 10189174
TI - Afterword: the cost of surrender.
PMID- 10189173
TI - Vibroacoustic disease: some forensic aspects.
AB - BACKGROUND: Vibroacoustic disease (VAD) is an insidious environmental entity
caused by occupational exposure to large pressure amplitude and low frequency
(LPALF) noise (> or = 90 dB SPL, < or = 500 Hz). Significant disabilities may
result, and issues of worker's compensation should be openly discussed and
settled. Toward this goal, a rigorous review of all available information on this
disease was undertaken in order to document the need to define industrial
exposure standards, and to settle on the diagnostic procedures that will help
distinguish the VAD from other, similar conditions. METHODS: We reviewed the
medical files of 236 male Caucasians employed as aircraft technicians who had
been diagnosed with VAD and monitored for at least 15 yr. The natural history of
the disorder was studied in detail, emphasizing the clinical diagnostic criteria
and the outcome of disabilities. RESULTS: Among the 236 cases, 172 (73%) were
disabled after an average of 24 yr (SD = 6.9) of occupational exposure. The
primary categories of disabilities were neurological (81, 34%), malignant (28,
11.9%), psychiatric (23, 9.7%), cardiovascular (16, 6.8%), and osteoarticular
(14, 5.9%). After the onset of industrial exposure to LPALF noise, the minimum
time for these disabilities to manifest themselves was 16 yr. The most serious
complication was multiple attempted suicide. Such attempts were fortunately rare
(5, 2.1%) and successful only once. Echocardiograms showed characteristic changes
in pericardial structures, involving proliferation of the extracellular matrix,
lack of cilia and five pericardial layers instead of three. This has been studied
in pericardial biopsy material obtained during coronary bypass surgery for
coronary insufficiency (six cases), and by autopsy (four cases). DISCUSSION:
These findings appear to be pathognomonic for the VAD, and the echocardiogram has
been confirmed as a fundamental diagnostic tool. The degree of disability due to
VAD can be determined from Portuguese national disability tables, which cover
almost all of the VAD-induced disabilities. However, these tables do not specify
LPALF noise as an occupational hazard, rendering them inapplicable to VAD
patients. Also, suicide, a most serious psychiatric consequence, is not covered
by these tables. Such situations highlight the absolute necessity to recognize
LPALF noise as the cause of VAD, and as an industrial hazard.
PMID- 10189175
TI - Solid-supported reagents in organic synthesis.
AB - The current interest in solid-phase organic synthesis has led to a renewed
interest in a complementary technique in which solid supported reagents are used
in solution phase chemistry. This technique obviates the need for attachment of
the substrate to a solid-support, and enables the chemist to monitor the
reactions using familiar analytical techniques. The purpose of this review is to
increase awareness of the wide range of useful transformations which can be
accomplished using solid-supported reagents.
PMID- 10189176
TI - 3-substituted GABA analogs with central nervous system activity: a review.
AB - Gabapentin and Pregabalin are both 3-alkylated gamma-amino butyric acid (GABA)
analogs. Gabapentin was designed as a lipophilic GABA analog and was first
synthesized as a potential anticonvulsant and was launched in 1994 as add-on
therapy for the treatment of epilepsy. In this review the discovery and
development of gabapentin as an anticonvulsant are discussed. During human trials
and while in clinical use, it became apparent that gabapentin induced some other
potentially useful therapeutic effects in chronic pain states and behavioral
disorders. A review of animal and clinical data relating to these other potential
therapeutic utilities is presented. Pregabalin was identified after an
investigation into other 3-substituted GABA analogs. It has since been shown to
have a similar pharmacological profile to gabapentin with greater potency in
preclinical models of pain and epilepsy. Studies of the mechanism(s) of action of
these compounds are discussed. Work towards identifying new analogs of both
gabapentin and pregabalin is also reviewed.
PMID- 10189177
TI - Small, noncovalent serine protease inhibitors.
AB - Thrombin and factor Xa (fXa) are the only serine proteases for which small,
potent, selective, noncovalent inhibitors have been developed, which are
ultimately intended as drug development candidates (in this case as
anticoagulants). Noncovalent inhibitors may be more selective and chemically and
metabolically less reactive than covalent inhibitors. In addition, noncovalent
inhibitors are more likely to have fast-binding kinetics which is particularly
important in the development of thrombin inhibitors. TAME derived noncovalent
thrombin inhibitors argatroban, napsagatran, and UK 156,406 have entered clinical
trials as anticoagulants, the latter as an orally active agent. Serine trap
deletion from substrate-like peptides led to the development of inogatran and
melagatran, both of which have entered clinical trials as intravenous agents. The
use of 3-aminopyridinone and pyrazinone acetamide peptidomimetic templates has
resulted in the development of L-375,378 which has been chosen for clinical
development as an orally active anticoagulant. Recently, compounds which do not
have the conventional hydrogen bonding capabilities of peptides have begun to
appear in the thrombin literature. Publications on noncovalent fXa inhibitors
cover this type of peptidomimetic almost exclusively.
PMID- 10189178
TI - Guidelines for calibration of stimulus and recording parameters used in clinical
electrophysiology of vision. Calibration Standard Committee of the International
Society for Clinical Electrophysiology of Vision (ISCEV).
AB - In order to perform a technically adequate clinical electrophysiological
procedure it is necessary to calibrate the stimulating and recording equipment.
Published standards for the electroretinogram (ERG), electro-oculogram (EOG),
visual evoked potential (VEP), and guidelines for the Pattern ERG (PERG) specify
stimulus and recording parameters. Yet, most commercial instruments do not
provide the means for calibration of these parameters. The goal of this document
is to provide guidelines for proper calibration of stimulus and recording
equipment. The need for such guidelines is clear on both clinical and scientific
grounds. Stimulus and amplifier characteristics have substantial effects on the
peak latency and amplitude measurements that are commonly used in clinical
electrophysiology. Many review articles on clinical electrophysiology emphasize
the need for establishing norms for each laboratory as a function of age and
gender rather than relying on published norms. However, if stimulus and recording
parameters are not calibrated periodically, then these norms may actually be
misleading due to changes in stimulus or recording conditions induced by aging of
equipment or inadvertent change in settings. This document is divided into two
major sections. The first is concerned with calibration of the visual stimulus.
It begins with background technical information on the physics of light and its
measurement. This is followed by protocols for measurement of the luminous
intensity of flash stimuli and the mean luminance, contrast, and visual angle of
pattern stimuli. The second section is concerned with calibration of
electrophysiologic recording systems. It begins with a description of the
characteristics of bioelectrical signals and their measurement. This is followed
by protocols for measurement of electrode impedance and amplifier calibration.
Although this document was prepared as guidelines for clinical
electrophysiological testing, it should be noted that the techniques described
are more generally applicable to studies which are dependent upon accurate
measurement of luminance or electrophysiological signals.
PMID- 10189179
TI - Comparison of guinea pig electroretinograms measured with bipolar corneal and
unipolar intravitreal electrodes.
AB - This study considers the precision and accuracy of bipolar corneal electrodes
compared with unipolar intravitreal methods in collecting electroretinographic
(ERG) recordings from a small animal. Flash ERGs were obtained from 9 adult
guinea pigs on three occasions. Corneal bipolar (Burian-Allen) electrodes were
used to collect data on the first two occasions whereas unipolar intravitreal
electrodes were used on the last. We identified the a-wave, b-wave, oscillatory
potentials, PIII and PII responses. Intensity-response functions were fit using a
Naka-Rushton relationship with a bootstrap estimating the 95% confidence limits.
Discrepancy analysis was applied to determine the coefficient of agreement. We
found significantly larger amplitudes with unipolar intravitreal electrodes
(ANOVA; a-wave, p<0.002; b-wave, p<0.001; Oscillatory potentials (OPs), p<0.005)
especially at high intensities. Implicit times showed little differences between
electrodes for the a-wave, significantly faster (p<0.03) b-waves at some
intensities, and significantly slower (p<0.005) OP implicit times across all
intensities. The PIlI amplitude (log microV), sensitivity and timing were not
significantly different (p>O.05) if expressed in logarithmic units but PII
amplitude (log microV) was significantly smaller with corneal electrodes. We
suggest that a conversion factor (x1.35) should be applied to data collected with
bipolar corneal electrodes to estimate the amplitudes of the modelled parameters
accurately. The corneal electrode gave a precision of +/-39 microV which yields a
statistical power of 0.90 for a sample size of 7 subjects. We conclude that
bipolar corneal electrodes provide smaller electroretinogram amplitudes due to
their location and reduced span of the retinal generators.
PMID- 10189180
TI - Evidence supportive of a functional discrimination between photopic oscillatory
potentials as revealed with cone and rod mediated retinopathies.
AB - We report on a family where four of the eleven children presented with reduced
visual acuities, a red-green deficit at the Farnsworth-Munsel FM 100-hue test,
normal appearing fundi and unexpected electroretinographic findings. Light-
(photopic) and dark- (scotopic) adapted electroretinograms (ERG) and oscillatory
potentials (OPs) were obtained following an accepted standard protocol. The b
wave of their photopic ERG was significantly more attenuated than the a-wave due
to the specific abolition of OP4, while the amplitudes of OP2 and OP3 were within
the normal range, giving to the b-wave a truncated appearance reminiscent of that
seen in congenital stationary night blindness (CSNB) with myopia. Interestingly
in the latter condition, which is believed to result from an ON-retinal pathway
anomaly, it is OP2 and OP3 which are specifically abolished while OP4 is of
normal amplitude thus resulting in an OP response pattern which complements that
seen with our patients. Also of interest is the fact that, in our patients, the
amplitude of the dark-adapted OP2 was, on average, 240% larger than that measured
in light-adaptation while, in normal, a non-significant 14% increase is noted; a
finding which is in keeping with other studies reporting supernormal scotopic
ERGs in some forms of cone dystrophies. Based on the photopic OP response
pattern, our patients represent the electrophysiological complement of patients
affected with CSNB. Interestingly their symptoms are also complementary, a
finding which could support a functional discrimination between the photopic OPs.
PMID- 10189181
TI - A simple and stable d.c.electrode for ocular electrophysiology.
AB - We describe the fabrication of a simple silver-silk electrode which permits
remarkably stable d.c.recording of the electroretinogram (ERG) and the optic
nerve response (ONR). A saline soaked wick of surgical silk, guided into a
polyethylene tube connects the tissue to a coil of Ag/AgCl wire placed in a small
glass vial, which is filled with 0.9% NaCl. The vial that holds the tube and the
wire is closed with a rubber cap allowing easy refilling with NaCl. Examples of
the usefulness of the new silver-silk electrode are shown. We applied it in
experimental work in the isolated arterially perfused cat eye for d.c.recordings
of the ERG and the optic nerve response (ONR), and also in vivo, in anesthetized
mice to record c-waves.
PMID- 10189182
TI - The VEP and ERG in a young infant with cystic fibrosis. A case report.
AB - We report a case of an infant with cystic fibrosis in whom VEP and scotopic ERG
abnormalities were found. The underlying cause of these findings, which could not
be determined within the limitations of this study, may be related to dietary
deficiencies.
PMID- 10189183
TI - Topography of the multifocal electroretinogram.
AB - The functional topography of the human retina was characterized using the
multifocal electroretinogram (ERG), with particular attention to the form of the
decline in response with retinal eccentricity. Population response variability
was examined and compared to standard full field ERG variability. Burian-Allen
contact lens electrodes were used to record the cone multifocal ERG from 50 young
eyes (28.3 years +/-5.9 years). Responses were recorded in 8 min from 103 retinal
locations within the central +/-22 degrees. The spatial distribution of local
responses showed an exponential fall-off with eccentricity. The exponential slope
parameter was highly similar across individuals. Excluding responses to the
central element, the fall off with eccentricity approximated a power function
with an exponent of -0.6, which compares to the -0.74 exponent for the human cone
density profile. The inter-individual variance in response density is greatest at
the central fovea, reducing towards more peripheral locations. The logarithm of
response density, however, shows approximately equal variance across
eccentricity, making log density a more appropriate way to view response
topography. The population range (+/-2 S.D.) of response density is 0.42 log
unit, similar to that of standardized ganzfeld electroretinography. The response
exponential decay provides a potentially useful addition to element-by-element
comparison, in deciding whether an eye's response is within normal limits.
PMID- 10189184
TI - Standardization notice: EOG standard reapproved. Electro-oculogram.
PMID- 10189185
TI - Cytotoxic T-lymphocyte responses to HIV-1 reverse transcriptase (review).
AB - Cytotoxic T lymphocytes (CTL) play an important role in the control of human
immunodeficiency virus (HIV) infection. CTL responses have been demonstrated for
most of the HIV gene products, predominantly gag, pol, and env-encoded proteins,
and also for the regulatory proteins Nef, Tat, Vif, or Rev. The HIV-1 reverse
transcriptase (RT), which derives from expression of the pol gene, is an
important target of cellular immune responses in infected individuals. More than
40 different peptides containing RT-specific CTL epitopes have been identified.
The most conserved and frequently detected are located in the 'fingers' and
'palm' subdomains of the enzyme, but other epitopes have been found in the
'thumb' and 'connection' subdomains as well as in the RNase H domain. Studies on
the sequence variability and functional role of amino acids forming CTL epitopes
are relevant for addressing important questions relative to viral escape from
immmune control and the future design of anti-AIDS vaccines.
PMID- 10189186
TI - Loss of antiviral cytotoxic T-lymphocyte activity during high-level antigen
stimulation.
AB - High levels of antigenic stimulation can result in deactivation of CD8+ T cells
through a variety of mechanisms, including insufficient T-cell help. In the
present study, an adoptive transfer system was established in which ovalbumin
(OVA)-specific CD8+ T cells were transferred to irradiated mice infected with a
recombinant vaccinia virus encoding OVA (VV-OVA). Prolonged activation of OVA
specific CD8+ T cells resulted in a proliferative block in these cells, although
cytotoxic function was maintained. Unlike naive and recently activated OVA
specific T cells, these nonproliferative cytotoxic CD8+ T cells did not have
antiviral activity following further transfer to mice infected with VV-OVA.
Provision of interleukin-2 (IL-2) at the site of virus infection using a
recombinant virus encoding antigen and IL-2, as well as the addition of helper T
cells, had no effect on the generation of these dysfunctional T cells. Thus,
there was no evidence that lack of T-cell help was responsible for CD8+ T-cell
deactivation in this model.
PMID- 10189187
TI - A single amino acid variation within an immunodominant AKR/Gross MuLV cytotoxic T
lymphocyte epitope leads to a loss in immunogenicity.
AB - C57BL/6 mice characteristically generate vigorous H-2K(b)-restricted cytotoxic T
lymphocytes (CTL) directed against an immunodominant CTL epitope (KSPWFTTL)
expressed by endogenous AKR/Gross murine leukemia viruses (MuLV). These AKR/Gross
MuLV-specific CTL do not efficiently recognize tumor cells induced by
Friend/Moloney/Rauscher (FMR) MuLV, which express the highly homologous peptide
RSPWFTTL. In this report, we not only confirm the inefficient recognition of FMR
tumors by AKR/Gross MuLV-specific CTL, but also demonstrate that RSPWFTTL is
poorly immunogenic in C57BL/6 mice. To gain insight into the mechanism(s)
contributing to the inefficient recognition of FMR MuLV-induced tumors, we
examined the RSPWFTTL dissociation rate from H-2K(b) as well as the ability for
RSPWFTTL to diminish CTL effector functions by T-cell antagonism. In contrast to
immunogenic peptides, which form stable MHC class I-peptide complexes having slow
dissociation rates, poorly immunogenic peptides characteristically have faster
dissociation rates. On the basis of a cell-surface MHC class I peptide
stabilization assay, the dissociation rate of RSP-WFTTL from H-2K(b) is
characterized by a half-life that is nearly identical to the half-life of
KSPWFTTL. In addition, we could find no evidence for antagonistic inhibition of
AKR/Gross MuLV-specific CTL over a wide concentration range of RSPWFTTL. Analysis
of the role of the transporter associated with antigen processing (TAP), by use
of recombinant vaccinia and Sindbis viruses expressing a hydrophobic amino
terminal endoplasmic reticulum (ER) targeting sequence coupled to RSPWFTTL,
indicated that RSPWFTTL cell-surface presentation can be dramatically enhanced
when directly targeted into the ER.
PMID- 10189188
TI - Distinct serum cytokines in AIDS-related skin diseases.
AB - To determine whether common skin diseases associated with human immunodeficiency
virus (HIV) were distinguishable based on the pattern of serum cytokine
expression, we studied patients with psoriasis, pruritus, and Kaposi's sarcoma
(KS) for levels of tumor necrosis factor (TNF)-alpha, interferon-gamma (IFN-y),
interleukin (IL)-10, and IL-4. Thirty-two HIV-positive (HIV+) patients including
8 with KS, 11 with psoriasis, and 13 with pruritus along with 16 HIV-negative
subjects with psoriasis were studied. IFN-gamma levels were highest in sera of
HIV+ patients with psoriasis (p = 0.040). By contrast, TNF-alpha and IL-10 levels
were highest in sera of HIV+ patients with pruritus (p = 0.012). Detectable
levels of all cytokines in these patients were remarkably higher than for healthy
adults. These results suggest that common skin diseases associated with HIV
infection and AIDS can be distinguished by the production of unique cytokines.
PMID- 10189189
TI - Induction of interleukin-10 on activation of Epstein-Barr virus in EBV-infected B
cell lines.
AB - Human (h) interleukin-10 (IL-10) exhibits a strong DNA and amino acid sequence
homology to the Epstein-Barr virus (EBV) BCRF1 genome, viral (v) IL-10. We
analyzed the production of IL-10 for EBV activation in B-cell lines. The latent
EBV in Akata cells was activated by the cross-linking of surface immunoglobulin G
(IgG) with anti-human IgG. The levels of IL-10(h+v) and vIL-10 in the culture
fluids were measured by a specific enzyme-linked immunosorbent assay (ELISA). IL
10(h+v) was detected at the same time for EBV immediate early gene BZLF1 product
ZEBRA and early gene BMRF1 product EA-D. This was more than 4 hours prior to the
appearance of vIL-10, and late gene products gp 350/220 and viral capsid antigen.
The induction of hIL-10 and vIL-10 mRNAs were detected in anti-IgG-treated Akata
cells by reverse transcription-polymerase chain reaction. The induction of IL
10(h+v) and vIL-10 was inhibited with a tyrosine kinase inhibitor, herbimycin, or
with an inhibitor of herpesvirus DNA polymerase, phosphonoacetic acid, or
acyclovir. IL-10(h+v) and vIL-10 were also detected in the supernatants of Akata
and Daudi but not Ramos cells infected with P3HR-1 EBV. These results show the IL
10 induction on EBV activation in EBV-carrying B-cell lines.
PMID- 10189190
TI - The effect of different bovine viral diarrhea virus genotypes and biotypes on the
metabolic activity and activation status of bovine peripheral blood mononuclear
cells.
AB - The effects of cytopathic (cp) and non-cytopathic (ncp) bovine viral diarrhea
virus (BVDV) on the cellular metabolic activity and activation status of bovine
peripheral blood mononuclear cells (PBMC) were investigated. Cellular DNA and
protein synthesis was determined by [3H]thymidine and [3H]valine incorporation,
respectively, in phytohemagglutinin (PHA)-stimulated PBMC. All cp strains and
most ncp BVDV strains significantly inhibited DNA synthesis in PHA-stimulated
PBMC; however, only cp BVDV strains inhibited protein synthesis. A plaque assay
and immunofluorescence test confirmed productive BVDV infection of PBMC. In
addition, viral RNA synthesis was demonstrated in BVDV-infected PBMC by RT-PCR.
The interleukin-2 receptor (IL-2R) was used as a marker for the activation status
of BVDV-infected PBMC. The expression of IL-2R was preserved in virus-infected
cells, even though DNA and protein synthesis was suppressed. These findings
suggest a novel mechanism of virus-induced immune suppression in which BVDV
inhibits basic metabolic activities of bovine PBMC. The activation signals,
however, are maintained.
PMID- 10189191
TI - Immunization against hepatitis B virus by mucosal administration of antigen
antibody complexes.
AB - Antigen-antibody complexes have been shown to enhance immune responses against
several antigens given by parenteral immunization. Herein, we have evaluated the
potential of administering such immunostimulatory complexes by a mucosal route.
Hepatitis B surface antigen (HBsAg) complexed with antibodies against HBsAg (anti
HBs) (HBsAg/Ab) was administered to BALB/c mice by intranasal inhalation. HBsAg
by itself did not induce immune responses, whereas with HBsAg/Ab complexes, both
systemic and mucosal immune responses were observed and these could be modulated
by adjuvants. With HBsAg/Ab (1 or 10 microg), anti-HBs antibodies induced were
predominantly of the IgG1 isotype (Th2-like). In contrast, anti-HBs induced by
HBsAg/Ab plus cholera toxin (CT) or oligodeoxynucleotides (ODN) containing
immunostimulatory CpG motifs (CpG) (1 microg each) were predominantly IgG2a (Th1
like). Results from this study indicate that HBsAg/Ab complexes can induce strong
humoral immune responses when delivered by a noninvasive route, whether used
alone or in combination with other mucosal adjuvants.
PMID- 10189193
TI - Preliminary studies on the prevalence of Mycoplasma bovis mastitis in dairy in
cattle in Australia.
AB - A highly sensitive and specific PCR (MB-PCR) was used in preliminary studies to
detect M. bovis in milk samples to investigate its association with high somatic
cell count (SCC), an indicator of subclinical mastitis and one of the factors in
down grading the quality of milk. A total of 186 and 167 herds were tested with
43% and 62% of herds positive for M. bovis in Victoria and North Queensland,
respectively. The quarter milks from 52 cows with persistently high SCC were
tested by MB-PCR and culture to investigate the association of M. bovis with
major mastitis pathogens (MMP). M. Bovis was detected in 77% of cows of which 19%
alone had M. bovis without any other bacteria, 17% had M. bovis in combination
with major mastitis pathogens and 40% had M. bovis in combination with non-major
mastitis pathogens. We believe that M. bovis is widespread in dairy cattle and
has the potential to produce disease alone or to predispose the udder to disease
caused by major mastitis and environmental pathogens. These studies have revealed
a hitherto unrecognised high prevalence of M. bovis in dairy cattle in North
Queensland and Victoria in Australia. These initial studies also give a clear
association between M. bovis and elevated somatic cell counts.
PMID- 10189192
TI - Oxidative activity of turkey monocytes, following the inoculation with Chlamydia
psittaci.
AB - Chemiluminescence (CL) was used to investigate the competence of turkey monocytes
to mount a respiratory burst response upon interaction with Chlamydia psittaci.
The oxidative activity of purified turkey monocytes, following inoculation with
the avian C. psittaci serovar D strain 92/1293, was studied using luminol- and
lucigenin-enhanced CL. Purified turkey monocytes were inoculated with C. psittaci
at multiplicity of infection (MOI) of approximately 100, 10 and 1. In the
presence of luminol, no detectable CL or only a weak CL response was obtained,
and if present it increased with increasing MOI. Either sham inoculated
monocytes, or monocyte-free control assays supplemented with C. psittaci, gave no
detectable luminol-enhanced CL responses. In the lucigenin-enhanced assays,
monocytes inoculated with C. psittaci demonstrated an immediate CL peak, the
height of which was proportional to the MOI used. Following inoculations at a MOI
1, a faint second peak was observed, when applying high concentrations of
lucigenin. Sham inoculated monocytes gave no detectable lucigenin-enhanced CL
responses. However, in the presence of lucigenin, the addition of C psittaci to
monocyte-free controls also resulted in an immediate CL peak, though no second
peak was detected. This immediate lucigenin-dependent CL peak induced by C.
psittaci was similar to the one observed in the presence of monocytes, and was
not inhibited by superoxide dismutase. We demonstrated that this avian C.
psittaci strain induces only a very weak respiratory burst response in turkey
monocytes. In contrast, C. psittaci itself elicited an intense non-superoxide
mediated lucigenin-dependent CL, indicating that in chlamydial research the
detection of superoxide, using lucigenin, should be confirmed with a specific
superoxide inhibitor.
PMID- 10189194
TI - Associations amongst three feline Porphyromonas species from the gingival margin
of cats during periodontal health and disease.
AB - Digoxigenin labelled whole chromosomal DNA probes directed against three feline
members of the genus Porphyromonas (P. gingivalis VPB 3492, P. circumdentaria
NCTC 12469T and P. salivosa VPB 3313) were used to identify and quantify
organisms in samples taken from the gingival margins of 40 domestic cats with
different grades of periodontal disease. At the right upper canine tooth, the
grade of periodontal disease ranged from 0 to 5 and the cfu of
facultative/obligate anaerobes ranged from 5.5 x 10(4) to 2.0 x 10(6)). In 38 of
the 40 cats, at least one of the three Porphyromonas species was isolated and
regression analysis showed that the cfu of total Porphyromonas sp. was a highly
significant indicator of the grade of periodontal disease (p < 0.001, R2 0.510).
Feline P. gingivalis was isolated from 37 of the 40 cats and regression analysis
showed that it was a highly significant predictor of the grade of periodontal
disease (p < 0.001, R2 0.561). The cfu of P. salivosa was a significant predictor
of the grade of periodontal disease (p < 0.001, R2 0.286) and regression analysis
showed that there was a significant positive relationship between cfu of P.
circumdentaria and grade of periodontal disease (p = 0.018, R2 0.116). The
periodontal grades at the right upper third premolar tooth ranged from 0 to 6.
The cfu of facultative/obligate anaerobes isolated ranged from 1.2 x 10(5) to 7.9
x 10(6), and regression analysis showed that cfu was a significant predictor of
periodontal grade (p < 0.001, R2 0.378). The cfu of total Porphyromonas species
ranged from 1.2 x 10(4) to 1.7 x 10(6) and regression analysis of the cfu against
the grade of periodontal disease showed a highly significant association (p <
0.001, R2 0.633). The cfu of P. gingivalis ranged from 0 to 1.1 x 10(6) and
regression analysis of the cfu of P. gingivalis against the grade of periodontal
disease showed a highly significant association (p < 0.001, R2 0.439). The cfu of
P. salivosa was a significant predictor of the grade of periodontal disease (p <
0.001, R2 0.479) and the same association was found between cfu of P.
circumdentaria and grade of periodontal disease (p = 0.002, R2 0.204). This study
has established Porphyromonas as anumerically significant and highly prevalent
genus in feline periodontal disease.
PMID- 10189195
TI - HPLC does not differentiate Mycobacterium paratuberculosis from Mycobacterium
avium.
AB - HPLC, which is gaining its place as identification tool in mycobacteriology
laboratories, has been proposed to distinguish Mycobacterium paratuberculosis
from Mycobacterium avium. We had reported no significant difference between M.
avium and M. paratuberculosis reference strain ATCC 19698. Because of the
advantages offered by such a method, we enlarged our observations to include more
isolates of M. paratuberculosis. Within the double cluster of peaks obtained by
both M. avium and M. paratuberculosis, we could not find a consistent difference
typical of M. paratuberculosis. Therefore, the present study confirmed that M.
avium and M. paratuberculosis could not be distinguished by HPLC, raising doubts
of a straightforward use of HPLC to identify M. paratuberculosis.
PMID- 10189196
TI - Identification of immunogenic, surface-exposed outer membrane proteins of
Pasteurella haemolytica serotype 1.
AB - Pasteurella haemolytica serotype 1 (S1) is the bacterium most frequently
recovered from the lungs of cattle that have succumbed to shipping fever
pneumonia. P. haemolytica outer membrane proteins (OMPs) are important immunogens
in the development of resistance to pneumonic pasteurellosis. The purpose of this
study was to identify the repertoire of immunogenic, surface-exposed P.
haemolytica (S1) OMPs, that could be important in the development of protective
immunity. We determined surface exposure of OMPs by (1) their susceptibility to
protease treatment and (2) their ability to adsorb out antibodies from bovine
immune sera. For a comprehensive identification of immunogenic, surface-exposed
OMPs, we used bovine antisera from calves that were resistant to experimental P.
haemolytica challenge after (1) natural exposure to P. haemolytica, (2)
vaccination with live P. haemolytica, or (3) vaccination with P. haemolytica
OMPs. We identified 21 immunogenic, surface-exposed P. haemolytica OMPs. Most
were recognized by all three immune sera. However, some were recognized by one or
two of the three antisera. Our analyses identified surface-exposed, immunogenic
proteins that were not identified in previous studies.
PMID- 10189197
TI - Monophasic group B Salmonella species infecting harbour porpoises (Phocoena
phocoena) inhabiting Scottish coastal waters.
AB - A monophasic strain of Salmonella group B having the antigenic structure 4, 12:
a: - was isolated in culture from various tissues of 39 harbour porpoises
(Phocoena phocoena). The tissue from which the organism was recovered most
frequently was lung in 33 animals and intestine in 16 animals, but it was also
isolated from heart valve, liver, kidney, spleen, mesenteric lymph node,
pulmonary lymph node, hepatic lymph node, urethra, sheath and epididymis. As far
as we are aware this is the first record of this strain from an animal source,
raising the possibility that it may be host-adapted to harbour porpoises. The
possible modes of transmission of monophasic group B Salmonella between porpoises
are discussed.
PMID- 10189198
TI - Cellular and humoral responses in the respiratory tract of goats following
intranasal stimulation using formalin-killed Pasteurella haemolytica A2.
AB - A study to determine the immunoglobulin and cellular responses in the respiratory
tract of goats following intranasal exposures to formalin-killed Pasteurella
haemolytica A2 was carried out. Forty-two goats were divided into two groups.
Goats in Group 1 were subjected to double intranasal exposures to formalin-killed
P. haemolytica A2 while goats in Group 2 were the unexposed control. Prior to and
at weekly intervals post-exposure, three goats from each group were killed, serum
samples were collected while the lungs were flushed with 50 ml normal saline
before the right apical lobes were fixed in 10% buffered formalin. Both serum and
lung lavage fluid were subjected to enzyme-linked immunosorbent assay (ELISA) to
determine the levels of IgA, IgM and IgG while the formalin-fixed tissues were
examined histologically. IgA levels in the lung lavage fluid increased rapidly to
reach a significantly (p < 0.05) high level as early as Week 2 post-exposure and
remained significantly (p < 0.05) high throughout the study period. The IgM
levels increased at an intermediate rate to reach a significantly (p < 0.05) high
level at Week 3 post-exposure before they decreased to an insignificant (p >
0.05) level the following week and the weeks thereafter. IgG levels increased
gradually and only reached a significantly (p < 0.01) high level at Weeks 5 and 6
of the study. The size of the bronchus-associated lymphoid tissue (BALT) and the
number of lymphocytes in BALT increased significantly from Week 2 and remained
high thereafter. However, differences in the numbers of BALT were insignificant
(p > 0.05) initially before becoming significantly (p < 0.05) high at Weeks 5 and
6. The BALT responses were parallel to those of imunoglobulins in the lung lavage
fluid.
PMID- 10189199
TI - Influence of age and plasma treatment on neutrophil phagocytosis and CD18
expression in foals.
AB - The aim of this study was to evaluate the influence of age and plasma treatment
on neutrophil phagocytosis, CD18 expression and serum opsonic capacity in foals
in field settings. Microbial infections constitute a large threat in young foals
and neutrophil functions are crucial for the defense. Blood samples were obtained
from 13 foals at seven time points between the ages of 2 and 56 days and once
from 16 adult horses. Six of the foals were treated with adult plasma at the age
of 1 week. Neutrophil phagocytosis of yeast after various opsonizations and the
expression of complement adhesion receptor CD18 were analysed by flow cytometry.
Autologous serum opsonization resulted in 52+/-6.1% phagocytic neutrophils in 2
day-old foals (n = 12), a significantly lower rate than in adult horses (mean
84+/-3.1%; n = 16). In foals, yeast ingestion per neutrophil was also lower than
in adults. Opsonic capacity increased with age (p < 0.05), reaching adult levels
at 3-4 weeks. An increase in serum opsonic capacity followed plasma treatment (p
< 0.05). The phagocytic capacity of foal neutrophils at the time-points studied
was equal to or higher than that in the adults, when pooled adult horse serum or
anti-yeast IgG was used as opsonin. In foals, serum IgG concentration was
negatively correlated to serum opsonic capacity. CD18 receptor expression was
higher in neutrophils from foals (<21 days old) than in those from adult horses
(p < 0.05). The results indicate that foals are transiently deficient in serum
opsonic capacity, which negatively affects their capacity for neutrophil
phagocytosis. These changes in serum opsonins, unrelated to IgG, may be important
factors in susceptibility to infections in foals.
PMID- 10189200
TI - [Influence of exposure to mercury, arsenic and antimony on body burden--a
biomonitoring study].
AB - Part of the northern Palatinate region in Germany is characterized by elevated
levels of mercury, arsenic and antimony in the soil due to the presence of ore
sources and former mercury mining activities. Today, the region is characterized
by housing and agriculture. In a biomonitoring study, 218 residents (age 1-89
years) were investigated for a putatively increased absorption of these elements
from the environment. 76 non-exposed subjects (age 2-84 years) of a region in
south lower Saxony (Germany) were chosen as a reference group. Urine and scalp
hair samples were obtained as surrogates to determine the internal exposures to
mercury, arsenic and antimony. In the northern Palatinate subjects slightly, yet
presumably not hazardous, elevated arsenic contents in urine and scalp hair could
be correlated to an increased arsenic content in the soil. On the other hand, the
results did not show a correlation between the mercury and antimony contents in
the soil of the housing area and those in urine and hair. Urinary mercury
contents were correlated with the total amalgam area in both study groups.
Mercury contents in scalp hair and arsenic contents in urine were correlated with
the consumption of seafood. Surprisingly, the geogenically non-exposed reference
subjects showed significantly higher internal exposures to arsenic and antimony
in urine and scalp hair. However, data of both groups correspond to normal range
reference data described by others.
PMID- 10189202
TI - Dynamic association of moesin with the membrane skeleton of thrombin- activated
platelets.
PMID- 10189201
TI - Mechanistic aspects of molybdenum-containing enzymes.
PMID- 10189204
TI - Hereditary spherocytosis due to a novel frameshift mutation in AE1 cytoplasmic
COOH terminal tail: band 3 Vesuvio.
PMID- 10189203
TI - Ex vivo factors affecting contact phase activation in negatively charged medical
devices.
PMID- 10189205
TI - Splenectomy in agnogenic myeloid metaplasia.
PMID- 10189206
TI - Dehydrated hereditary stomatocytosis is not linked to the hlK1 locus, a Gardos
channel candidate, on chromosome 19q13.2.
PMID- 10189207
TI - C282Y hemochromatosis mutation does not contribute to hypercoagulability in a
factor V Leiden population referred to venous thrombosis.
PMID- 10189208
TI - Comparative analysis of autografting in chronic myelogenous leukemia: effect of
priming regimen and marrow or blood origin of stem cells.
PMID- 10189209
TI - Routine screening of children returning home from the tropics: retrospective
study.
PMID- 10189210
TI - Call to needle times after acute myocardial infarction. Acute myocardial
infarction at sea can be treated promptly.
PMID- 10189211
TI - Call to needle times after acute myocardial infarction. In Sandwell, patients are
advised to dial 999 rather than call their GP.
PMID- 10189212
TI - Sentinel node biopsy in breast cancer. Arguments for node biopsy are weak.
PMID- 10189213
TI - Sentinel node biopsy in breast cancer. Value is already proved.
PMID- 10189214
TI - Avoiding the consequences of deep vein thrombosis. Patients can participate in
management.
PMID- 10189215
TI - Communicating risk reductions. One example is not enough.
PMID- 10189216
TI - Communicating risk reductions. Researchers should present results with both
relative and absolute risks.
PMID- 10189217
TI - Communicating risk reductions. Modifying risk is different to treating illness.
PMID- 10189218
TI - Perinatal death associated with planned home birth in Australia. Study prompts
several questions.
PMID- 10189219
TI - Severe autosomal dominant retinitis pigmentosa caused by a novel rhodopsin
mutation (Ter349Glu). Mutations in brief no. 208. Online.
AB - Mutations in the rhodopsin gene are reported to be responsible for approximately
25% of all cases of autosomal dominant Retinitis pigmentosa (adRP). Affected
individuals from a large family with an unusually severe form of adRP were
screened for mutations in the rhodopsin gene. Direct sequencing of exon 5
revealed a TAA to GAA transversion at nucleotide 5276/codon 349, which was
confirmed by Dde1 restriction digest analysis. This change would replace the
normal termination codon with a glutamic acid residue (Ter-349-Glu, or X349E).
The next predicted termination codon (TAA) lies 153bp downstream at nucleotides
5429 to 5431. Termination of transcription at this point would add an additional
51 amino-acid residues to the carboxy terminus of the rhodopsin molecule. This
mutation is unique in producing a mutant rhodopsin in which all of the normal 348
amino-acid residues remain intact. It produces one of the most severe adRP
phenotypes ever observed in a family with a rhodopsin mutation. In view of this
the Ter-349-Glu mutation is worthy of further investigation to determine how the
presence of this particular mutant opsin leads to rod photoreceptor degeneration.
PMID- 10189220
TI - Novel mutations in African American patients with glycogen storage disease Type
II. Mutations in brief no. 209. Online.
AB - The infantile form of GSD II (an inherited deficiency of the lysosomal enzyme,
acid alpha-glucosidase, Pompe disease) is a severe and invariably fatal disease
characterized by a rapidly progressive generalized hypotonia, hepatomegaly, and
cardiomegaly. We have recently demonstrated that African American patients share
a common nonsense R854X mutation in exon 18 (Becker et al., 1998). Two other
mutations, D645E and M519V, have been identified in individual African American
patients (Hermans et al., 1993a; Huie et al., 1994a). We describe here three
novel mutations in this population group: a missense W481R in exon 10, a deletion
of a T1441 in exon 10, and a splicing defect at the 5' donor site of intron 8
(IVS g+la) . The splicing defect is shared by two unrelated patients and it is
linked to intragenic polymorphic sites identical to those found in patients
bearing the common R854X mutation.
PMID- 10189221
TI - Expansion of CTG repeat in myotonin protein kinase gene on Alu(ins)-HinfI-I
background in a myotonic dystrophy patient from India. Mutations in brief no.
210. Online.
AB - To determine the founder of Indian myotonic dystrophy mutation, we have studied
the expansion of CTG repeats in myotonin protein kinase gene and two intragenic
linked loci Alu(ins) / Alu(del) and G/T intron 9 HinfI polymorphism in ten
unrelated DM patients from eastern India. Out of these ten patients,
reconstruction of haplotype was possible for five patients unambiguously. In the
other five cases, haplotype for the normal allele was assumed to be the most
common haplotype found in normal individuals from Indian populations. Such
analysis showed that in nine cases, the expansion of CTG repeats took place on
Alu(ins)-HinfI-2 background indicating common founder with other DM mutation
published. However, in one case we observed a different haplotype [Alu(ins)-HinfI
1] which could be a new mutation or due to admixture.
PMID- 10189222
TI - Identification of 8 new mutations in Brazilian families with Marfan syndrome.
Mutations in brief no. 211. Online.
AB - Marfan Syndrome (MFS) is a connective tissue disease caused by mutations in the
fibrillin-1 FBN1) gene. Screening for mutations in all the 65 exons of the FBN1
gene in 34 unrelated patients were performed to compare the efficiency of SSCP
versus Heteroduplex analysis and to verify if the spectrum of mutations in
Brazilian patients is similar to the one previously reported. Fourteen different
band shifts were detected by SSCP analysis; among these only 6 were also were
also detected through Heteroduplex analysis, suggesting that SSCP analysis was a
more efficient method. Except for one, the molecular alteration was confirmed in
the remaining 13 cases by sequencing; five of them were neutral polymorphisms and
the eight others are new pathogenic mutations, as follows: 5 missense, one
nonsense and two deletions leading to a premature termination codon (PTC). All of
them are located in EGF-like-calcium binding motifs (EGF-like-cb). Our findings
reinforce that cysteine substitutions and PTC mutations in the region between
exons 24-32 are more likely not to be associated with the neonatal phenotypes.
PMID- 10189223
TI - Hydrophobicity.
PMID- 10189224
TI - Mycobacterium avium subsp. paratuberculosis in Crohn's disease is serologically
positive.
PMID- 10189226
TI - Molecular studies of diabetes reported at the Fourth European Congress of
endocrinology.
AB - In his lecture at the Fourth European Congress of Endocrinology, C.R. Kahn
considered the effects of knock-out of genes encoding the proteins involved into
insulin signal transduction on the development of insulin-resistance and non
insulin-dependent diabetes mellitus. The latter were induced in animals by
knockout of genes encoding insulin receptors and intracellular substrate proteins
of the insulin receptor. Using special technology, the authors achieved selective
knock-out of the insulin receptor gene in muscles and pancreatic beta-cells of
mice. Non-insulin-dependent diabetes mellitus developed only after the knock-out
of the insulin receptor gene in beta-cells and resulted from the inability of
glucose to penetrate into beta-cells and stimulate insulin secretion. The
insensitivity of muscles to insulin due to the lack of its receptor did not
result in diabetes. In these animals insulin and glucose blood level did not
differ from the control values, but blood lipid concentration was increased. For
the cases of the reduction in the insulin-dependent penetration of glucose into
muscles, these data may indirectly indicate a transition of energy metabolism in
muscles from carbohydrate utilization to increased fat consumption as an energy
source.
PMID- 10189225
TI - Microsatellite polymorphisms in Bolivian squirrel monkeys (Saimiri boliviensis).
AB - Two different approaches were used to identify new microsatellite polymorphisms
among captive Bolivian squirrel monkeys (Saimiri boliviensis). In the first case,
PCR primers for published human microsatellite loci were screened using genomic
DNA from squirrel monkeys. Six polymorphic loci were identified using DNA samples
from 19 unrelated individuals. The average heterozygosity among these six loci is
0.73. In the second set of experiments, a DNA library was created from Saimiri
genomic DNA, and clones were selected from that library by screening with probes
containing di-, tri-, and tetranucleotide repeats. Six novel microsatellites were
identified this way, with an average heterozygosity of 0.59. Primer pairs for
these six cloned microsatellites were also screened using a series of DNA samples
from ten other platyrrhine species to assess the potential utility of these loci
in other taxa. This study provides 12 new DNA polymorphisms that will be useful
for various studies of this genus and demonstrates that both approaches can be
used to develop new DNA polymorphisms in platyrrhine species.
PMID- 10189227
TI - 1998 Nobel prize winners for physiology or medicine.
PMID- 10189228
TI - Utilization of ELISA technology to measure biological activities of carbohydrates
relevant in disease status.
AB - Since its discovery in 1960, ELISA technology has been utilized in an increasing
number of biological and biochemical investigations. It has proven to be one of
the most powerful tools available for probing recognition processes involving
protein/protein, protein/glycoprotein, protein/glycolipid and
glycoprotein/glycolipid interactions. This review begins with an introduction
that provides an historical perspective on the development of ELISA followed by a
description of the different classifications of this assay. One of the
fundamental elements of ELISA is the adhesion of a molecule of interest to a
solid support, generally a microtiter plate. Recent developments in the area of
adhesion and adsorption are also presented. Although ELISA has been used most
extensively in studying protein/protein interactions, in the past 10 years there
have been a number of advances in ELISA technology that have allowed recognition
processes involving carbohydrates to be studied. This review focuses on the use
of ELISA in investigating diseases where carbohydrate recognition processes are
implicated. Since studies related to the HIV virus have provided a major impetus
for the advancement of ELISA technology, this area of research is highlighted.
PMID- 10189229
TI - Alpha-Gal oligosaccharides: chemistry and potential biomedical application.
AB - This article focuses on the most recent research efforts by the Wang group in the
field of alpha-Gal oligosaccharides. alpha-Gal oligosaccharides are carbohydrate
structures bearing a Gal( alpha)1-3Gal(beta) terminus. This class of compounds
are believed to act as xenoactive antigens that instigate the hyperacute
rejection in xenotransplantation. Enzymatic methods using recombinant (alpha)1-3
galactosyltransferase were employed to synthesize several alpha-Gal
oligosaccharides. In addition, a chemical synthetic scheme was devised in order
to produce readily accessible amounts of alpha-Gal. Conformational analysis was
done using both NMR techniques and molecular modeling protocols. These studies
provide important information in the structure-function relationship of alpha-Gal
and anti- alpha-Gal antibodies.
PMID- 10189230
TI - Thio sugars: biological relevance as potential new therapeutics.
AB - The biological relevance of sulfur containing carbohydrates is gaining
substantial attention. Thus the new developments, especially in the synthetic and
medicinal chemistry of thio-sugars are critically important for carbohydrate drug
design. New studies of biological processes including biosynthetic reactions and
enzyme control mechanisms, discovered during the last few years clearly
contributed to an understanding of their biological roles. These roles of
carbohydrates and thio-sugars in particular through biological processes and
diseases are becoming better understood now. These new trends will provide
tremendous opportunities for the development of carbohydrates as new potential
drugs. The main objective of this article is to address these new promising
advances
PMID- 10189231
TI - Antibacterial effect of some 2,6-disubstituted 4-anilinoquinazolines.
AB - Two synthetic 2,6-disubstituted 4-anilinoquinazolines exerted a significant
effect on the G+ bacteria Bacillus subtilis and staphylococcus aureus. None of 12
tested derivatives influenced Escherichia coli, Proteus mirabilis and Pseudomonas
aeruginosa. Derivatives having the aromatic ring non-substituted or substituted
by bromine, the pyrimidine ring by phenyl, morpholine or piperidine and the
aniline skeleton non-substituted or substituted by methyl or amino group exerted
a considerable antibacterial activity.
PMID- 10189232
TI - Genotype distributions of hepatitis C virus in Sao Paulo, Brazil: rare subtype
found.
PMID- 10189233
TI - Liver failure in protoporphyria: long-term treatment with oral charcoal.
PMID- 10189234
TI - Resistance of hepatitis B to antiviral agents.
PMID- 10189235
TI - Quantification of serum hepatitis C virus RNA.
PMID- 10189236
TI - Low frequency of CYP2B deletions in Brazilian patients with congenital adrenal
hyperplasia due to 21-hydroxylas deficiency.
AB - The frequency of large mutations was determined in 131 Brazilian patients with
different clinical forms of 21-hydroxylase deficiency, belonging to 116 families.
DNA samples were examined by Southern blotting hybridization with genomic CYP21
and C4cDNA probes after Taql and Bg/II restriction. Large gene conversions were
found in 6.6% and CYP21B deletions in 4.4% of the alleles. The breakpoint in
these hybrid genes occurred after exon 3 in 92% of the alleles. All
rearrangements involving CYP21B gene occurred in the heterozygous form, except in
a patient with simple virilizing form who presented homozygous CYP21B deletion.
Our data showed that in these Brazilian patients, CYP21B deletions were less
frequent than in most of the large series previously reported.
PMID- 10189237
TI - [Local anesthesia in endonasal paranasal sinus operations].
PMID- 10189238
TI - Specific skin manifestations in CD56 positive acute myeloid leukemia.
AB - We found 16 CD56+ cases (29.6%) among 54 acute myeloid leukemia (AML) patients;
they showed significantly frequent cutaneous involvement compared to CD56- cases
(43.8% vs. 15.8%, p<0.05). Four of the CD56+ AML cases with specific skin
manifestations were reviewed histologically. In all cases, cutaneous leukemic
cells were seen in the dermis and subcutaneous tissue with accentuation around
the adnexa/nerve, but sparing the epidermis. In addition, angiocentric/
angiodestructive and prominent cohesive tumor cell growth were seen in two cases,
respectively. These findings suggest that the expression of CD56 may often be
associated with the cutaneous involvement in AML, and that the above histological
findings should remind us of the possibility of specific skin manifestations in
CD56+ AML.
PMID- 10189239
TI - Quantitative study of mast cells in Kimura's disease.
AB - The association of mast cells with typical lesions of Kimura's disease was
investigated by quantitative methods after immunohistochemical staining for
Factor VIII-related antigen and counterstaining with toluidine blue. Formalin
fixed, paraffin-embedded, tissue sections from 9 confirmed cases of Kimura's
disease were examined after staining to estimate mast cell and blood vessel
densities by counting 100 random fields under oil immersion. There was a
statistically significant increase of both mast cells and blood vessels in
Kimura's disease (p<0.01) compared with normal skin and reactive lymph node
controls. However, as far as the individual Kimura's disease lesion is concerned,
there was generally no correlation between areas with mast cell increase and the
degree of vascularity. Moreover, when lesions of less than 1 year's duration were
compared with older lesions, there appeared to be a relative decrease in mast
cells and a concomitant increase in vascularity in the latter. These results
confirmed that mast cells are associated with Kimura's disease, and suggest that
they may be involved in its early pathogenesis, although its possible role in
angiogenesis may not be direct.
PMID- 10189240
TI - ICAM-3 and E-selectin endothelial cell expression differentiate two phases of
angiogenesis in infantile hemangiomas.
AB - Cellular adhesion molecules are newly identified mediators of angiogenesis.
Infantile hemangiomas, characterized in the early stages by a proliferation of
poorly differentiated vessels followed in the late stages by a vascular
differentiation and regression of the tumor, represent an interesting model to
study angiogenesis. We studied by immunohistochemistry the distribution of HLA-DR
and three adhesion molecules ICAM-3, E-selectin and VCAM-1 on endothelial cells
in different stages of vessel differentiation in infantile hemangiomas. We found
high levels of ICAM-3 expression on proliferating vessels, while its expression
was low or undetectable on well differentiated vessels. A different set of E
selectin antibodies showed a more heterogenous pattern of distribution and VCAM-1
antigens were found in both proliferating and differentiated vessels. HLA-DR
expression on endothelial cells was inversely correlated to the vascular
differentiation. Our results are consistent with the hypothesis that ICAM-3 plays
a role in the early stages of vessel formation. Our results also suggest that
variation of E-selectin and HLA-DR expression may be related either to vessel
differentiation or may reflect the acquisition of an activated endothelial cell
status.
PMID- 10189241
TI - Spiny keratoderma--a demonstration of hair keratin and hair type keratinization.
AB - Six cases of spiny keratoderma were analyzed with hair specific antikeratin
antibodies (AE13, AE14) and by electron microscopy. The keratotic column
exhibited a different keratin birefringence and the underlying viable epidermis
was less eosinophilic than the surrounding epidermis. AE13, which is specific for
hair cortex, was positive in the lower column and variably positive in the viable
epidermis, often beyond the columnar lesion. AE14 was negative in the lesion.
Electron microscopy demonstrated features of keratinization of normal hair
cortex, i.e. by the accretion of keratin filaments without production of
keratohyalin or trichohyalin granules. Cementsomes (lamellar granules) and
marginal bands were not produced as they are not formed in normal cortical
keratinization. It was suggested that spiny keratoderma represents an ectopic
hair formation of palms and soles.
PMID- 10189242
TI - Neural spectrum: palisaded encapsulated neuroma and verocay body poor dermal
schwannoma.
AB - We examined 25 palisaded encapsulated neuromas (PEN) of the skin and used
peripherin antibody as an immunohistochemical label for axons. Quantitative
analysis of the axon to schwann cell nuclear ratio for each PEN was determined by
examining cross-sectioned neuroid fascicles. This revealed that 120 of the 253
cross-sectioned fascicles in PEN lacked axon and only 5% of the fascicles had an
axon to schwann cell nuclear ratio greater than 1:2. In contrast, all fascicles
in 40 dermal nerves adjacent to PENs as well as 35 traumatic neuromas in surgical
scars had an axon to schwann cell nuclear ratio of at least 1:2 and the majority
a ratio of 1:1 or higher. These results suggest that there is a spectrum between
PENs which are axon rich to a form of schwannoma with an identical histopathology
which lacks significant axonal content and that not all PENs are true neuromas.
PMID- 10189243
TI - Repeat direct immunofluorescence (DIF) test, using, 1 M NaCl treated skin, in the
subepidermal autoimmune bullous diseases that contain IgG at the dermal epidermal
junction.
AB - Knowledge of autoimmune bullous diseases has greatly increased with the
recognition of new entities, and the use of the direct immunofluorescence (DIF)
using 1 molar per liter of sodium chloride (1 M NaCl) treated skin has been
proposed. To estimate the frequency with which the different DIF patterns are
present, we performed a systematic study of the skin or oral mucosa samples in
which linear deposits of IgG at the basement membrane zone were detected by
routine DIF in the last 6 years. The DIF tests were done on 56 samples before and
after splitting the epidermis from the dermis with 1M NaCl. In 40 biopsies (72%)
IgG was found on either the epidermal side or on both sides after 1M NaCl split.
These cases corresponded to bullous pemphigoid (n=33), herpes gestationis (n=5)
and cicatricial pemphigoid (n=2). In 6 cases (10.7%), IgG deposits were observed
only on the floor, five corresponding to bullous pemphigoid and one to bullous
pemphigoid-like eruption induced by amoxicillin. Repeat direct immunofluorescence
using 1M NaCl split skin indicates that at least 12% of patients who were
initially diagnosed as bullous pemphigoid, may in fact suffer a different entity,
requiring other techniques to achieve the right diagnosis. This test can be a
useful routine screening for autoimmune bullous diseases.
PMID- 10189244
TI - Pseudoporphyria associated with Relafen therapy.
AB - Various oral medications including nonsteroidal anti-inflammatory drugs (NSAIDs)
have been associated with pseudoporphyria, although the pathogenetic basis has
not been elucidated. A novel NSAID nabumetone (Relafen) has become popular
because of its minimal gastrointestinal side effects. Its association with
pseudoporphyria is not reported save for its listing in the Physician's Desk
Reference (PDR) as a possible side effect. Biopsies of lesional skin from 4
patients manifesting blisters and erosions on the hands and face within 4 months
of starting nabumetone were submitted for light microscopic and immunofluorescent
(IF) studies. Histories and serology were obtained. Two patients had rheumatoid
arthritis (RA), 1 had mixed connective tissue disease (MCTD), and 1 received
diltiazem. All 4 had antinuclear antibodies. Characteristic clinical, light
microscopic and IF features in the absence of elevated urine porphyrin levels
confirmed a diagnosis of pseudoporphyria in all 4 patients. Biopsies in three
patients showed features attributed to underlying connective tissue disease
(CTD), including ectasia of the superficial vascular plexus, mild
leukocytoclastic vasculitis, superficial and deep perivascular lymphocytic
infiltrates with dermal mucinosis, granular deposition of IgM along the
dermoepidermal junction indicative of a positive lupus band test, and of IgG and
C5b-9 within keratinocytes. Nabumetone (Relafen) can provoke pseudoporphyria; an
underlying CTD diathesis may be a predisposing factor.
PMID- 10189245
TI - Microcystic adnexal carcinoma arising in the setting of previous radiation
therapy.
AB - While there are several reports of microcystic adnexal carcinoma developing in
patients within sites of previous therapeutic irradiation, this relationship is
not well described in the dermatologic literature. We report a case of a 42-year
old man with a remote history of therapeutic irradiation following surgical
resection of periorbital rhabdomyosarcoma. Subsequently, he developed multiple
basal cell carcinomas and a microcystic adnexal carcinoma within the field of
irradiation. The histologic features were those of a classic microcystic adnexal
carcinoma, with well differentiated nests and cords of keratinocytes displaying
follicular and ductular differentiation infiltrating diffusely into the reticular
dermis. Dense fibrosis was present surrounding the neoplastic keratinocytes.
Nuclear atypia and mitotic figures were not identified. A carcinoembryonic
antigen (CEA) stain demonstrated glandular differentiation. It is important for
dermatologists to be aware of the apparent relationship between the rare
microcystic adnexal carcinoma with its innocuous scar-like clinical appearance
and prior local radiation therapy.
PMID- 10189246
TI - Syphilis in an HIV infected patient misdiagnosed as leprosy.
AB - A 42-year-old man with uveitis and a widespread cutaneous eruption,
histopathologically characterized by dermal granulomatous infiltrates with
perineurial invasion, was incorrectly diagnosed and treated as having borderline
leprosy. Further studies demonstrated secondary syphilis and human
immunodeficiency virus (HIV) infection. Standard penicillin therapy resolved his
cutaneous and ocular lesions. Reports on clinical and pathological findings of
active syphilis in HIV infected patients are scarce but this case and isolated
previous case reports suggest that granulomatous infiltrates might be a common
feature in secondary syphilis with short evolution in HIV infected patients.
PMID- 10189247
TI - Birt-Hogg-Dube syndrome and Hornstein-Knickenberg syndrome are the same.
Different sectioning technique as the cause of different histology.
AB - The autosomal dominant inherited syndromes of Hornstein and Knickenberg (HKS),
and Birt, Hogg and Dube (BHDS) are both characterized clinically by the overall
spread of multiple flesh coloured papules of the skin. However, it is a matter of
debate if colonic neoplasms (adenomas as well as adenocarcinomas) are associated
findings in the HKS or rather in the BHDS. Furthermore, histological differences
are said to exist between the skin lesions in the two syndromes: whereas
perifollicular fibromas were described in the HKS, fibrofolliculomas and
trichodiscomas were found in the BHDS. In the present study, we report on a
father and his daughter in whom we initially diagnosed a BHDS. We then examined a
greater number of the papular lesions in histologic sections cut vertically as
well as horizontally to the epidermis. Our results indicate that the histologic
differences between the skin lesions in the two syndromes are artificial ones,
caused by interpretation of different sectioning planes, and that consequently
HKS and BHDS are the same. Therefore, it is necessary to look for colonic polyps
in the syndrome in question, regardless if one prefers the name HKS or BHDS for
it.
PMID- 10189249
TI - In memoriam: Emmanuel van der Schueren.
PMID- 10189248
TI - Mainly unmutated V(H) genes rearranged in B cells forming germinal centers in a
cutaneous pleomorphic T-cell lymphoma.
AB - B cells in skin lesions of a pleomorphic cutaneous T-cell lymphoma with reactive
germinal center hyperplasia were analyzed for their immunoglobulin V(H)DJ(H) gene
rearrangements by micromanipulation and single cell polymerase chain reaction
(PCR) analysis. In B lymphocytes located in germinal center-like structures, we
found in 11/16 different V(H)DJ(H) rearrangements completely unmutated VH genes,
suggesting that those cells did not undergo antigen-driven selection. Two V(H)
genes showed more than 98% germ-line identity. In only three cells V(H) segments
were somatically mutated to a higher extent, but two of these rearrangements were
non-productive. These results differ markedly from what we have previously
detected in B cells present in mycosis fungoides, another entity of cutaneous T
cell lymphomas where the Ig gene repertoire resembles the situation in peripheral
blood with a significantly higher proportion of mutated V(H) genes. When
investigating the large atypical B cells strongly expressing CD30 which were
detected within the T-cell zone outside the germinal centers, we found again, in
most cases, that the rearranged VH genes were completely unmutated. The B cells
were of polyclonal origin. Due to this comparable Ig gene repertoire and
mutational pattern, we suggest that these cells descend from the germinal center
centroblasts which migrated into the T-cell zone and obviously became stimulated
to express the CD30 marker. The micromanipulation technique and molecular
analysis on the single cell level may provide an important input into our
understanding of the mechanisms of immune regulation in cutaneous lymphomas.
PMID- 10189250
TI - End-of-life decision making.
PMID- 10189251
TI - Dietary supplements: an important component of alternative medicine curricula.
PMID- 10189252
TI - Use of immobilized artificial membrane chromatography for drug transport
applications.
PMID- 10189253
TI - Permeability of cornea, sclera, and conjunctiva: a literature analysis for drug
delivery to the eye.
AB - The objective of this study was to collect a comprehensive database of ocular
tissue permeability measurements found in a review of the literature to guide
models for drug transport in the eye. Well over 300 permeability measurements of
cornea, sclera, and conjunctiva, as well as corneal epithelium, stroma, and
endothelium, were obtained for almost 150 different compounds from more than 40
different studies. In agreement with previous work, the corneal epithelium was
shown generally to control transcorneal transport, where corneal stroma and
endothelium contribute significantly only to the barrier for small, lipophilic
compounds. In addition, other quantitative comparisons between ocular tissues are
presented. This study provides an extensive database of ocular tissue
permeabilities, which should be useful for future development and validation of
models to predict rates of drug delivery to the eye.
PMID- 10189254
TI - Development of a single-shot subunit vaccine for HIV-1. 5. programmable in vivo
autoboost and long lasting neutralizing response.
AB - The subunit vaccine for HIV-1, recombinant glycoprotein 120 (rgp120), was used as
a model antigen to evaluate the potential for a pulsatile single immunization
vaccine formulation consisting of poly(lactic-co-glycolic) acid (PLGA)
microspheres. We designed rgp120 PLGA microsphere formulations that provide a
pulse of rgp120 at 1 to 6 months (depending on the polymer) after administration,
mimicking another immunization. In these studies, the in vitro pulse of rgp120
correlated well with the observed in vivo autoboost as measured by an increase in
anti-gp120 antibodies in guinea pigs. The immune response to the rgp120 PLGA
microsphere formulations was increased by adding the soluble form of the saponin
derived adjuvant, QS-21. The use of small microspheres, however, did not increase
the humoral response to rgp120. A single immunization with rgp120 PLGA
microspheres resuspended in soluble rgp120 and QS-21 elicited neutralizing
antibody titers that were comparable to titers obtained from two immunizations of
rgp120 and QS-21 at the same total dose. Administration of rgp120 PLGA
microspheres in baboons resulted in high, long-lasting neutralizing antibody
titers that were greater than repeated immunizations with soluble rgp120 and QS
21. These studies also indicated that a continuous release of QS-21 at the
injection site may provide a greater immune response than a bolus injection.
Overall, this work demonstrated that PLGA microsphere formulations may be
designed to provide in vivo pulses of an antigen eliminating the need for
repeated immunizations.
PMID- 10189255
TI - A crystallographic and molecular modeling study of butyrophenones.
AB - The X-ray crystal structures of four butyrophenone analogues have been completed
and are reported herein. These include spiperone hydrochloride (I), N
methylspiperone hydrochloride (II), pimozide (III), and fluspirilene (IV). These
structures were compared to other structurally similar molecules with similar
pharmacological activity. In addition, a molecular modeling study was done in
order to determine the low energy conformations of these molecules. It was found
that calculations of parameters that describe the molecular conformations showed
that all four molecules were structurally similar. Crystallographic data: [see
text]
PMID- 10189256
TI - Human cytochromes P450 mediating phenacetin O-deethylation in vitro: validation
of the high affinity component as an index of CYP1A2 activity.
AB - Phenacetin O-deethylation, widely used as an index reaction for cytochrome P450
1A2 (CYP1A2) activity, displays biphasic kinetics in human liver microsomes.
CYP1A2 has been identified as contributing to the high affinity component, but is
not verified as the sole contributor to the high affinity phase. In addition, the
human CYP isoforms accounting for the low affinity phase have not been
identified. We have used heterologously expressed human CYP isoforms to identify,
kinetically characterize, and predict the relative contribution of the major
human liver CYP isoforms mediating phenacetin O-deethylation. CYP1A2 (Km 31
microM) is the only high affinity phenacetin O-deethylase in human liver
microsomes, while CYPs 2A6 (Km 4098 microM), 2C9 (Km 566 microM), 2C19 (Km 656
microM), 2D6 (Km 1021 microM), and 2E1 (Km 1257 microM) all contribute to the low
affinity phase of the reaction. Considering the relative abundance of the various
CYPs in human liver, CYP1A2 accounts for 86% of net reaction velocity at a
substrate concentration of 100 microM, while CYP2C9 becomes the primary
phenacetin O-deethylase at substrate concentrations of 865 microM and higher and
accounts for 31% of the net Vmax of the reaction. Predictions from kinetic
studies on heterologously expressed CYPs are consistent with chemical inhibition
studies on human liver microsomes with sulfaphenazole and alpha-naphthoflavone
that suggest a greater role for CYP2C9, and a smaller role for CYP1A2, at higher
substrate concentrations. Thus CYP1A2 is the only high affinity human liver
phenacetin O-deethylase, thereby validating the use of the high affinity
component as an index of CYP1A2 activity in human liver microsomes.
PMID- 10189257
TI - Ion mobility across human stratum corneum in vivo.
AB - The aim of this study was to develop methods to determine ionic transport
parameters, in particular ionic mobilities across human stratum corneum (SC) in
vivo. It has been shown previously that the SC, a structurally heterogeneous
biomembrane, behaves as a homogeneous barrier to water transport; that is, water
diffusivity does not vary as a function of position within the SC; in this work,
therefore, the question posed was whether ion motion behaved similarly. Low
frequency impedance measurements (1.61 Hz) reported on the decrease of SC
impedance as the barrier was progressively removed by serial adhesive tape
stripping. This corresponded to an increase in ion mobility of approximately 2
orders of magnitude across the SC (from the external surface to the interior).
Therefore, an algorithm was developed from the absolute impedance data to
calculate ion mobility as a function of position within (i.e., depth into) the
SC. The mobilities deduced from the algorithm correlated well with water
permeability across the SC. The data presented here are thought to be the first
measurements of ionic mobility across human skin in vivo.
PMID- 10189258
TI - A novel thermogravimetric method for estimating the saturated vapor pressure of
low-volatility compounds.
AB - Thermogravimetric analysis is used to measure accelerated vaporization rates at
elevated temperatures and reduced pressures for several compounds. Multiple
linear regression is used to generate empirical coefficients of an equation that
relates these parameters. The vaporization rates of the compounds at standard
ambient temperature and pressure (SATP) are estimated by extrapolation to 10(5)
Pa (1 atm) and 298 K. The estimated vaporization rates are then correlated with
literature values of saturated vapor pressure (Psat). The results of twenty four
compounds with vapor pressures that span 10 orders of magnitude indicate that p25
degrees C (sat) is directly proportional to the rate of vaporization at SATP. The
average error of an estimate of p25 degrees C (sat) based on this relationship is
less than a factor of 2.1.
PMID- 10189259
TI - In vivo fate of folate-BSA in non-tumor- and tumor-bearing mice.
AB - KB tumor cells exhibit an increased number of folate receptors on their membrane.
This receptor has been proposed as a promising target for tumor drug targeting.
Therefore, the disposition of folate-conjugated bovine serum albumin (folate-BSA)
was examined as a model system for drug targeting. Nude mice which had received
KB tumor cell transplants were given bolus intravenous administration of either
111In-labeled folate-BSA (111In-folate-BSA; 1 mg/kg) or unmodified 111In-BSA
(111In-BSA; 1 mg/kg). The disposition characteristics and pharmacokinetics of
111In-folate-BSA were compared with those of the 111In-BSA as a control. The half
life of the beta-phase of 111ln-folate-BSA in plasma was 140 min. The tumor
uptake rate index for 111In-folate-BSA was 0.46 microL/min/g, and that for 111In
BSA was 0.32 microL/min/g. This index of 111In-folate-BSA was slightly higher
than that of 111In-BSA in vivo, by a factor of 1.4. In vivo experiments showed
folate-BSA has a relatively long plasma duration. 111In-folate-BSA also showed
selective distribution to tumors, but not as great as recent results from in
vitro experiments. Therefore, the low vascular permeability of BSA into solid
tumor tissue and inhibition of folate-mediated 111In-folate-BSA uptake by tumor
cells from the blood may be the rate-limiting factor of distribution.
PMID- 10189260
TI - Drug compatibility with the sponge phases formed in monoolein, water, and
propylene glycol or poly(ethylene glycol).
AB - The liquid sponge phase, a bicontinuous lipid-water system, formed in solvent
monoolein-water systems was investigated with respect to drug compatibility. The
solvents propylene glycol and poly(ethylene glycol) swell the bicontinuous cubic
phase of the monoolein-water system and form the sponge phase at constant water
contents, 40 and 30% w/w, respectively. Amphiphilic drugs such as lidocaine
participate in the bilayer and act on the interfacial curvature according to the
amphiphilic packing concept. The interfacial curvatures increase/decrease
depending on the salt/base forms of the molecules. The quantity of lidocaine that
can be incorporated into the sponge phase depends not only on the form of
lidocaine but also on the lipid content and the solvent used in the sponge phase.
Addition of the water-insoluble gramicidin S to the sponge phase resulted in a
stiff isotropic phase, possibly a cubic phase, indicating interaction of
gramicidin S with the lipid bilayer. The in vitro release of lidocaine was
significantly faster from the sponge phase in the propylene glycol system than
from the corresponding cubic phase without solvent.
PMID- 10189261
TI - Controlled, multidose, pharmacokinetic evaluation of two extended-release
carbamazepine formulations (Carbatrol and Tegretol-XR).
AB - A major limitation of conventional carbamazepine (CBZ) formulations is their
pharmacokinetics, which typically require q.i.d. dosing. Two extended-release
formulations of CBZ have been developed recently to support b.i.d. dosing. One,
Carbatrol (CBTL) uses immediate-, extended-, and enteric-release beads in a
capsule. The other, Tegretol-XR (TXR), uses an osmotic pump (Oros tablet). To our
knowledge, this is the first head-to-head comparison of the multidose
pharmacokinetics of these two new formulations. The objective of the study was to
evaluate the pharmacokinetics of carbamazepine (CBZ) and CBZ-10,11-expoxide (CBZ
E) after multidose b.i.d. dosing with CBTL or TXR. In this randomized, crossover
study, 15 normal healthy adults received 400 mg of each formulation b.i.d. for 5
days. Blood samples for CBZ and CBZ-E analysis were obtained prior to morning
doses on all days and hourly for 12 h after the Day 5 dose. There was a minimum
interperiod washout of 9 days. For CBTL and TXR, the key CBZ pharmacokinetic
measures of area under the curve of concentration versus time (AUC(0-tau)),
maximum concentration (Cmax), and minimum concentration (Cmin) were
bioequivalent. The ratio for CBTL-to-TXR was 98% (90% confidence intervals, 92
104%), 107% (96-118%), and 96% (89-104%), respectively. Similar ratios were also
observed for CBZ-E: 102% (97-107%), 99% (92-107%), and 93% (83-109%),
respectively. In conclusion, CBTL b.i.d. and TXR b.i.d. were bioequivalent in
their pharmacokinetic parameters for CBZ and CBZ-E after 5 days of dosing.
PMID- 10189262
TI - Combined effect of complexation and pH on solubilization.
AB - Both pH control and complexation are widely used as solubilization techniques in
drug formulation studies. Although these two techniques are often utilized in
combination, few theoretical studies have shown why the combined approach would
work better than either one alone. This study constructs a background in which
both the pH effect and complexation constants are used to explain the synergism
between these techniques. The total solubility is determined by the addition of
the concentrations of the four components present in the solution: free un
ionized drug [Du], free ionized drug [Di], un-ionized drug complex [DuL], and
ionized drug complex [DiL]. A detailed description of [Di] and [DiL] reveals that
the complexation constants and the pH at which the drug may ionize are both
critical. The weakly basic drug flavopiridol is used as a test compound to
examine the validity of the equation. Although the complexation constant for
ionized flavopiridol (Ki = 124 M(-1)) is less than one-third of that of the un
ionized species (Ku = 445 M(-1)), the solubility of the ionized drug complex
[DiL] is 6-fold greater than that of the un-ionized drug complex [DuL]. This
unexpected result is due to the 25-fold greater solubility of the ionized drug
[Di] at pH 4.3 over that of the free un-ionized species [Du] at pH 8.4. The
results of this and other complexation studies of several drugs taken from the
literature lend the support to the following: If [Di]/[Du] >Ku/Ki, then [DiL]
>[DuL].
PMID- 10189263
TI - Metabolism of halofantrine to its equipotent metabolite, desbutylhalofantrine, is
decreased when orally administered with ketoconazole.
AB - Halofantrine (Hf) is a highly lipophilic antimalarial with poor and erratic
absorption. Published data indicates that the oral bioavailability of Hf was
increased 3-fold in humans and 12-fold in dogs when administered postprandially;
however, the proportional formation of the active desbutyl metabolite
(desbutylhalofantrine, Hfm) decreased 2.4-fold in humans and 6.8-fold in dogs
(Milton et al., Br. J. Clin. Pharmacol. 1989, 28, 71-77; Humberstone et al., J.
Pharm. Sci. 1996, 85, 525-529). The current study was undertaken to confirm the
putative involvement of CYP3A4 in the N-dealkylation of Hf to Hfm by
administering Hf with and without ketoconazole (KC), a specific CYP3A4 inhibitor,
and measuring the resulting plasma concentration profiles of Hf and Hfm. The
plasma Hfm/Hf AUC(0-72 h) ratio after fasted oral administration of Hf without KC
was 0.56, whereas the ratio after fasted oral administration with KC was less
than 0.05. It is likely that both hepatic and prehepatic (enterocyte-based)
CYP3A4 contributed to metabolism of Hf to Hfm after oral administration.
Interestingly, the low plasma Hfm/Hf AUC ratios observed after fasted
administration of Hf with KC were similar to the low values previously observed
when Hf was administered postprandially (despite increased Hf absorption). The
mechanism(s) by which postprandial administration of Hf led to a decrease in its
metabolism are unknown, but based on the current data, could include inhibition
of CYP3A4-mediated metabolism by components of the ingested meal. Other
possibilities include a lipid-induced postprandial recruitment of intestinal
lymphatic transport or avoidance of metabolism during transport through the
enterocyte into the portal blood. Further studies are required to determine the
relative contributions by which these different processes may decrease the
presystemic metabolism of Hf.
PMID- 10189265
TI - Ephedrine-type alkaloid content of nutritional supplements containing Ephedra
sinica (Ma-huang) as determined by high performance liquid chromatography.
AB - Nutritional supplements containing Ephedra sinica (ma-huang), a botanical source
of ephedrine-type alkaloids, have been linked to numerous episodes of ephedrine
(EPH) toxicity. With passage of the 1994 Dietary Supplement Health and Education
Act, nutritional supplements are no longer subject to the same FDA preapproval
requirements as food additives, prescription, or nonprescription medications. As
a consequence, EPH content is not a label requirement for Ephedra-containing
supplements. Less stringent labeling requirements, therefore, may contribute to
toxicity associated with these products. A validated HPLC method for the
determination of ephedrine-type alkaloids, commonly found in Ephedra supplements,
is presented. Nine commercially available supplements exhibited considerable
variability in alkaloid content (EPH range: 1.08-13.54 mg). Only three products
listed EPH content on the label while one exhibited lot to lot variations in EPH
of 137%.
PMID- 10189264
TI - Improvement of L-dopa absorption by dipeptidyl derivation, utilizing peptide
transporter PepT1.
AB - In the present study, possible enhancement of intestinal absorption of L-dopa by
utilizing intestinal peptide transporter was examined using Caco-2 cells and
Xenopus oocytes expressing human peptide transporter (hPepT1). To see whether
this peptide transporter could be utilized for the improvement of L-dopa
absorption, we employed a dipeptide-mimetic derivative of L-dopa, L-dopa-L-Phe. L
Dopa-L-Phe inhibited the uptake of [14C]Gly-Sar, but not that of L-[3H]-dopa by
Caco-2 cells. Uptake of L-dopa-L-Phe was increased by expression of hPepT1 in
Xenopus oocytes. The appearance of L-dopa and its metabolite, dopamine, on the
basolateral side of Caco-2 cells was significantly higher after addition of L
dopa-L-Phe than after that of L-dopa and was reduced by the presence of Gly-Sar
on the apical side. These results indicate that the L-dopa-L-Phe is absorbed more
efficiently than L-dopa and is taken up via the peptide transporter, but not via
the amino acid transporter, demonstrating the possibility of targeting the
peptide transporter as a means for improving intestinal absorption of peptide
like drugs.
PMID- 10189266
TI - Tween protects recombinant human growth hormone against agitation-induced damage
via hydrophobic interactions.
AB - In the absence of surfactants, recombinant human growth hormone (rhGH) rapidly
forms insoluble aggregates during agitation. The nonionic surfactant Tween 20,
when present at Tween:protein molar ratios >4, effectively inhibits this
aggregation. Differential scanning calorimetry (DSC) of rhGH solutions showed
melting transitions that decreased by ca. 2 degrees C in the presence of Tween.
Circular dichroism (CD) studies of the same thermal transition showed that the
decrease is specific to the relatively high protein concentrations required for
DSC. CD studies showed melting transitions that decreased with lower protein
concentrations. Tween has an insignificant effect on the melting transition of
rhGH at lower protein concentrations (0.18 mg/mL). Injection titration
microcalorimetry showed that the interaction of Tween with rhGH is characterized
by a weak enthalpy of binding. For comparison, interferon-g, another protein
which has been shown to bind Tween, also shows weak enthalpy of binding.
Fluorescent probe binding studies and infrared spectroscopic investigations of
rhGH secondary structure support suggestions in the literature (Bam, N. B.;
Cleland, J. L., Randolph, T. W. Molten globule intermediate of recombinant human
growth hormone: stabilization with surfactants. Biotechnol. Prog. 1996. 12, 801
809) that Tween binding is driven by hydrophobic interactions, with little
perturbation of protein secondary structure.
PMID- 10189268
TI - Origins of the unusual hygroscopicity observed in LY297802 tartrate.
AB - Hygroscopicity is an important physical property of drug materials, which can
significantly impact physicochemical stability and bulk processing and handling
characteristics. Although moisture sorption behavior is routinely investigated
for pharmaceutical compounds, the nature of water-solid interactions is generally
not well-understood at the molecular level for nonstoichiometric or variable
hydrates. The unusual hygroscopic behavior of the muscarinic agonist, LY297802
tartrate, has been investigated using moisture sorption analysis, solid-state NMR
(SSNMR) spectroscopy, and X-ray crystallography. LY297802 tartrate shows a unique
tendency to form nonstoichiometric hydrates of variable, but specific,
composition, with water content varying continuously from 0 to 0.5 mol
(hemihydrate). The propensity of this crystal form to rapidly equilibrate with
the humidity in the environment may be rationalized in terms of a sequential
migration of the weakly bound water of hydration in to and out of readily
accessible hydrogen-bonding sites in the lattice.
PMID- 10189267
TI - Inclusion complexation of ziprasidone mesylate with beta-cyclodextrin sulfobutyl
ether.
AB - Ziprasidone is an antipsychotic agent indicated primarily for the treatment of
schizophrenia. An intramuscular dosage form of ziprasidone was developed using
beta-cyclodextrin sulfobutyl ether (SBECD) to solubilize the drug by
complexation. Inclusion complexation of ziprasidone mesylate (ZM) with SBECD was
studied by circular dichroism (CD) spectroscopy, proton nuclear magnetic
resonance (1H NMR) spectroscopy, Monte Carlo simulations, phase-solubility
studies, and counterion titration. The results of the studies indicate that ZM,
of which the counterion is not fully dissociated from the drug, forms a 1:1
inclusion complex with SBECD with the benzisothiazole group positioned in the
cavity. A mathematical model was developed to calculate stability constants of
inclusion complexes for the ion pair (Z+M-:SBECD) and the dissociated ionic form
(Z+:SBECD) of ZM; the values were 7892 and 957 M(-1), respectively. The model
also allowed the dissociation constants of noncomplexed and complexed ZM to be
calculated; the value of the former is 8-fold greater than the value of the
latter. These results indicate that the inclusion complex formation of the ion
pair is favored over that of the dissociated ionic form of ZM, and that the
dissociation of ZM is suppressed by inclusion complexation with SBECD.
PMID- 10189269
TI - Influence of pH, temperature and buffers on cefepime degradation kinetics and
stability predictions in aqueous solutions.
AB - First-order rate constants (k) were determined for cefepime degradation at 45,
55, 65, and 75 degrees C, pH 0.5 to 8.6, using an HPLC assay. Each pH-rate
profile exhibited an inflection between pH 1 and 2. The pH-rate expression was
k(pH) = kH1 f1(aH+) + kH2 f2(aH+) + ks + kOH(aOH-), where kH1 and kH2 are the
catalytic constants (M(-1) h(-1)) for hydrogen ion activity (aH+), kOH is the
catalytic constant for hydroxyl ion activity (aOH-), and ks is the first-order
rate constant (h(-1)) for spontaneous degradation. The protonated (f1) and
unprotonated (f2) fractions were calculated from the dissociation constant, Ka =
(8.32x10(-6))e(5295)/RT where T was absolute temperature (T). Accelerated loss
due to formate, acetate, phosphate, and borate buffer catalysis was
quantitatively described with the catalytic constant, kGA (M(-1) h(-1)) for the
acidic component, [GA], and kGB (M(-1) h(-1) for the basic component, [GB], of
each buffer. The temperature dependency for each rate constant was defined with
experimentally determined values for A and E and the Arrhenius expression, kT =
Ae-E/RT, where kT represented kH1, kH2 , kS, kOH, kGA, or kGB. Degradation rate
constants were calculated for all experimental pH, temperature, and buffer
conditions by combining the contributions from pH and buffer effects to yield, k
= k(pH) + kGA[GA] + kGB[GB]. The calculated k values had <10% error for 103 of
the 106 experimentally determined values. Maximum stability was observed in the
pH-independent region, 4 to 6. Degradation rate constants were predicted and
experimentally verified for cefepime solutions stored at 30 degrees C, pH 4.6 and
5.6. These solutions maintained 90% of their initial concentration (T90) for
approximately 2 days.
PMID- 10189270
TI - Precursor-dependent indirect pharmacodynamic response model for tolerance and
rebound phenomena.
AB - A precursor-dependent model of indirect pharmacodynamic response which can
describe tolerance and rebound was characterized in terms of the effects of
changes in the fundamental properties of the drug on its response profiles. The
model extends previous models by considering inhibition or stimulation of
production of the response variable dependent on the amount of precursor which
may accumulate or deplete after administration of some drugs. Standardized
pharmacokinetic and pharmacodynamic parameters were used for generating dose,
plasma concentration, and response-time profiles using computer simulations. The
peak response (Rmax) and the time of its occurrence (TRmax) were dependent on the
dose, degree of maximum inhibition (Imax) or stimulation (Smax), and drug
concentrations causing 50% inhibition (IC50) or stimulation (SC50). The maximum
rebound (RBmax) and the time of its occurrence (TRBmax) after a single bolus dose
were also dependent on these factors, but were of lesser magnitude and showed
relatively later occurrence. Interestingly, values of area between the baseline
and effect curve (ABEC) and area between the baseline and rebound curve (ABRC)
were equal for each set of conditions for each model, but the latter is reduced
when there is a second pathway for loss of precursor. Tolerance occurs because of
diverse mechanisms, and the response patterns demonstrated may be helpful in
describing tolerance and rebound phenomena for drugs which affect precursor
pools.
PMID- 10189271
TI - Solubility enhancement of phenol and phenol derivatives in perfluorooctyl
bromide.
AB - Perfluorinated solvents are gaining popularity as pulmonary ventilation fluids,
but they suffer from poor solvent quality in concurrent drug delivery
applications. The present study examines the use of a hydrophobic solubilizing
agent capable of interacting with model drug solutes by hydrogen bonding with the
purpose of enhancing solubility in perfluorooctyl bromide (PFOB). A series of
solubilizing agents containing a ketone carbonyl to act as a hydrogen bond
acceptor and a perfluoroalkyl chain to maintain the solubility of the putative
complex in PFOB are investigated. The solubility of phenol in PFOB is enhanced to
the greatest extent by 1-(4-perfluorobutyl phenyl)-1-hexanone (III) where the
ketone carbonyl is protected from the electron withdrawing effects of the
perfluorobutyl chain by a phenyl ring. Experiments with solubilizers lacking the
ketone group suggest that pi-pi bond interactions of III with phenol do not
significantly enhance solubility. For a series of phenol derivatives, a rank
order correlation exists between the magnitude of solubility enhancement by III,
as reflected by the calculated association constants, and the Hammett sigma
parameter of the phenols. Because the O-methyl-substituted phenols do not have
the ability to hydrogen bond, their solubility is not enhanced by the presence of
III. The results of the present study indicate that solubility of model drug
hydrogen bond donating compounds can be enhanced in PFOB by the presence of
fluorocarbon-soluble hydrogen bond acceptors.
PMID- 10189272
TI - Enthalpy-entropy compensation for the solubility of drugs in solvent mixtures:
paracetamol, acetanilide, and nalidixic acid in dioxane-water.
AB - In earlier work, a nonlinear enthalpy-entropy compensation was observed for the
solubility of phenacetin in dioxane-water mixtures. This effect had not been
earlier reported for the solubility of drugs in solvent mixtures. To gain insight
into the compensation effect, the behavior of the apparent thermodynamic
magnitudes for the solubility of paracetamol, acetanilide, and nalidixic acid is
studied in this work. The solubility of these drugs was measured at several
temperatures in dioxane-water mixtures. DSC analysis was performed on the
original powders and on the solid phases after equilibration with the solvent
mixture. The thermal properties of the solid phases did not show significant
changes. The three drugs display a solubility maximum against the cosolvent
ratio. The solubility peaks of acetanilide and nalidixic acid shift to a more
polar region at the higher temperatures. Nonlinear van't Hoff plots were observed
for nalidixic acid whereas acetanilide and paracetamol show linear behavior at
the temperature range studied. The apparent enthalpies of solution are
endothermic going through a maximum at 50% dioxane. Two different mechanisms,
entropy and enthalpy, are suggested to be the driving forces that increase the
solubility of the three drugs. Solubility is entropy controlled at the water-rich
region (0-50% dioxane) and enthalpy controlled at the dioxane-rich region (50
100% dioxane). The enthalpy-entropy compensation analysis also suggests that two
different mechanisms, dependent on cosolvent ratio, are involved in the
solubility enhancement of the three drugs. The plots of deltaH versus deltaG are
nonlinear, and the slope changes from positive to negative above 50% dioxane. The
compensation effect for the thermodynamic magnitudes of transfer from water to
the aqueous mixtures can be described by a common empirical nonlinear
relationship, with the exception of paracetamol, which follows a separate linear
relationship at dioxane ratios above 50%. The results corroborate earlier
findings with phenacetin. The similar pattern shown by the drugs studied suggests
that the nonlinear enthalpy-entropy compensation effect may be characteristic of
the solubility of semipolar drugs in dioxane-water mixtures.
PMID- 10189273
TI - Effect of Tween 20 on freeze-thawing- and agitation-induced aggregation of
recombinant human factor XIII.
AB - Agitation- and freeze-thawing-induced aggregation of recombinant human factor
XIII (rFXIII) is due to interfacial adsorption and denaturation at the air-liquid
and ice-liquid interfaces. The aggregation pathway proceeds through soluble
aggregates to formation of insoluble aggregates regardless of the denaturing
stimuli. A nonionic surfactant, polyoxyethylene sorbitan monolaurate (Tween 20),
greatly reduces the rate of formation of insoluble aggregates as a function of
surfactant concentration, thereby stabilizing native rFXIII. Maximum protection
occurs at concentrations close to the critical micelle concentration (cmc),
independent of initial protein concentration. To study the mechanistic aspects of
the surfactant-induced stabilization, a series of spectroscopic studies were
conducted. Electron paramagnetic resonance spectroscopy indicates that binding is
not occurring between Tween 20 and either the native state or a folding
intermediate state of rFXIII. Further, circular dichroism spectroscopy suggests
that Tween 20 does not prevent the secondary structural changes induced upon
guanidinium hydrochloride-induced unfolding. Taken together, these results imply
that Tween 20 protects rFXIII against freeze-thawing- and agitation-induced
aggregation primarily by competing with stress-induced soluble aggregates for
interfaces, inhibiting subsequent transition to insoluble aggregates.
PMID- 10189274
TI - Link between drug absorption solubility and permeability measurements in Caco-2
cells.
AB - The objective of this investigation was to establish a relationship between drug
permeability and solubility in vitro and the extent of drug absorption in humans.
We selected drugs with varying permeabilities and solubilities with the aim of
establishing a relationship between permeability and solubility measurements in
vitro and the extent of absorption in vivo. Effective permeability coefficients
of the model drugs (naproxen, phenytoin, propranolol, diltiazem, salicylic acid,
ephedrine, cimetidine, chlorothiazide, and furosemide) at 37 degrees C and pH 7.2
were estimated using the Caco-2 cell line. Saturation solubilities of the model
drugs were estimated at pH 7.2 and at 37 degrees C. Data obtained from the
permeability and solubility experiments were employed in classifying the drugs
into high and low permeability-solubility groups. The permeability coefficients
ranged from 1x10(-7) to 4x10(-5) cm/s, and a good correlation was observed
between the permeability coefficients in Caco-2 cells and percent absorbed in
humans. Drugs in the high permeability, high solubility class are completely
absorbed (90% or higher). The study results indicate that there is a strong link
between permeability measured in Caco-2 cells, solubility, and fraction of drug
absorbed in humans.
PMID- 10189275
TI - Structural characterization of two polymorphic forms of piroxicam pivalate.
AB - The crystal and molecular structures of two polymorphs of piroxicam pivalate are
presented and discussed. A peculiarity of the high melting (154 degrees C)
polymorph is the association of piroxicam pivalate molecules as centrosymmetric
dimers by hydrogen bonding. Two centrosymmetrically related N-H...N hydrogen
bonds maintain the dimer structure involving the amido nitrogen atom as donor and
the pyridine nitrogen atom as acceptor. Molecular association of this type does
not occur in the crystal structures of drugs belonging to the oxicam class of
nonsteroidal antiinflammatory drugs. Two distinct conformations coexist in the
crystal of the low melting polymorph (136 degrees C) with differing hydrogen
bonding arrangements within domains of the crystallographically independent
molecules. The occurrence of different molecular conformations (conformational
polymorphism) associated with different hydrogen bonding schemes in discrete
domains is an unusual structural feature. Structural data for the two polymorphs
are also correlated with the relevant infrared spectra. Computer-generated X-ray
powder diffraction patterns for the two polymorphs of piroxicam pivalate are in
very good agreement with the experimental ones, thus confirming the validity of
the single-crystal X-ray models.
PMID- 10189276
TI - Sugar-polymer hydrogen bond interactions in lyophilized amorphous mixtures.
AB - The objective of this work was to investigate hydrogen bonding interactions
between a variety of glass-forming sugars and a model polymer,
poly(vinylpyrrolidone) (PVP), in binary amorphous solid solutions, produced by
lyophilization. The glass transition temperatures of the sugars and sugar-PVP
colyophilized mixtures were assessed using differential scanning calorimetry. The
hydrogen bonding interactions between each sugar and PVP were monitored using FT
Raman spectroscopy. Sucrose was found to hydrogen bond to a greater extent with
PVP at a particular sugar:polymer ratio than the other disaccharides studied
including trehalose and the trisaccharide raffinose. Maltodextrins showed a
decreased tendency to hydrogen bond with the polymer compared to the lower
molecular weight sugars. The extent of hydrogen bonding was found to correlate
inversely with the glass transition temperature of the sugar, with the tendency
to hydrogen bond decreasing as the Tg increased. The importance of hydrogen
bonding interactions to the thermodynamics of mixing in amorphous solids is
discussed.
PMID- 10189277
TI - In vitro evaluation of acyloxyalkyl esters as dermal prodrugs of ketoprofen and
naproxen.
AB - A series of acyloxyalkyl esters of ketoprofen and naproxen were synthesized and
investigated as topical prodrugs with the aim of improving the dermal delivery of
the drugs. In addition, some hydroxyalkyl esters of ketoprofen and naproxen were
synthesized as possible intermediates of acyloxyalkyl prodrugs. All of the
prodrugs were more lipophilic than their parent molecules, as evaluated by drug
partitioning between 1-octanol and phosphate buffer at pH 7.4 (log Papp).
However, their solubilities in aqueous solutions decreased markedly compared with
the parent molecules. The prodrugs were stable toward chemical hydrolysis in
aqueous solutions (pH 7.4), but were hydrolyzed to the parent drug both in 80%
human serum and in human skin homogenate, with half-lives ranging from 4 to 137
min and from 13 to 403 min, respectively. The abilities of the selected naproxen
acyloxyalkyl prodrugs to deliver naproxen through excised human skin were
evaluated. Generally, the prodrugs showed similar dermal delivery as the parent
drug through cadaver skin. In the present series of lipophilic prodrugs of
naproxen, the prodrug with the highest aqueous solubility was the most effective
prodrug to deliver naproxen through the skin.
PMID- 10189278
TI - Modeling of sertindole pharmacokinetic disposition in healthy volunteers in short
term dose-escalation studies.
AB - The pharmacokinetics of sertindole were studied in young, healthy volunteers
after single and multiple oral dose administered under an escalating manner. In a
low-dose study (study 1), subjects received 4-8 mg with a maintenance dose period
of 7 days. In a high-dose study (study 2), subjects received 4 mg daily for 2
days, and the dose was increased by 4 mg increments every third day until
reaching 20 mg daily. The mean terminal t 1,2 was 73 h after the final 8 mg dose
in study 1 and 60 h after the 20 mg dose in study 2. The terminal elimination
phase appeared to be monophasic in all the study subjects, suggesting that
Michaelis-Menten saturable metabolism was not involved in the elimination of
sertindole. Compartmental analyses suggested that the disproportional increase of
the Cmax and AUC values from 4 mg to 20 mg during multiple dosing may be
explained by saturable presystemic elimination of sertindole, leading to a higher
fraction of sertindole available for absorption at higher doses.
PMID- 10189279
TI - Deaggregation during the dissolution of benzodiazepines in interactive mixtures.
AB - The purpose of this research was to investigate the influence of surfactants on
the dissolution of benzodiazepines in interactive mixtures. The dissolution of
ternary interactive mixtures consisting of micronized drugs (oxazepam,
nitrazepam, and flunitrazepam) and micronized surfactants (sodium lauryl sulfate
and cetrimide) adhered onto the surface of a lactose carrier (250-355 microm) was
studied using the USP/NF paddle method. Dissolution was considered to occur from
dispersed particle and aggregate fractions of the drugs, and data were modeled
using multiexponential equations. The initial concentrations of the aggregates
and dissolution rate constants were estimated using a Marquardt-Levenberg
nonlinear least squares algorithm. The marked increase in dissolution rate which
occurred with increasing concentrations of sodium lauryl sulfate and cetrimide
resulted both from deaggregation of the benzodiazepine particles and from
increases in the dissolution rate constants of the dispersed particle and
aggregate fractions probably associated with an increased intrinsic dissolution
rate. The presence of 5% sodium lauryl sulfate in the interactive mixture reduced
the initial percent of aggregates from about 85% in a binary mixture to less than
10% and about doubled the dispersed particle dissolution rate constant. The
presence of the surfactant in the surface particulate matrix of the interactive
mixture was essential for its deaggregation effect. Sodium lauryl sulfate was
more effective than cetrimide in achieving drug deaggregation.
PMID- 10189280
TI - Effect of hydroxypropyl-beta-cyclodextrin and pH on the solubility of levemopamil
HCl.
AB - Levemopamil was solubilized by varying the concentration of hydroxypropyl-beta
cyclodextrin (HPbetaCD) and by the alteration of pH. The drug molecule has two
sites for possible complexation with HPbetaCD, creating the possibility of either
1:1 or 1:2 complexation. The solubility as a function of HPbetaCD concentration
of the charged and uncharged forms of the drug follows the A(L) and Ap
complexation models, respectively. This suggests that the charged drug forms a
1:1 complex, whereas the neutral drug forms both 1:1 and 1:2 complexes.
PMID- 10189281
TI - Short courses of zidovudine and perinatal transmission of HIV.
PMID- 10189282
TI - Short courses of zidovudine and perinatal transmission of HIV.
PMID- 10189283
TI - Short courses of zidovudine and perinatal transmission of HIV.
PMID- 10189284
TI - Short courses of zidovudine and perinatal transmission of HIV.
PMID- 10189285
TI - Treatment of acute promyelocytic leukemia with arsenic trioxide.
PMID- 10189286
TI - Treatment of acute promyelocytic leukemia with arsenic trioxide.
PMID- 10189287
TI - Human herpesvirus 8 and renal transplantation.
PMID- 10189288
TI - Human herpesvirus 8 and renal transplantation.
PMID- 10189289
TI - Prevention of second primary tumors by an acyclic retinoid in patients with
hepatocellular carcinoma.
PMID- 10189290
TI - Clinical problem-solving: diagnosis of tuberculous meningitis.
PMID- 10189291
TI - Clinical problem-solving: diagnosis of tuberculous meningitis.
PMID- 10189292
TI - Clinical problem-solving: diagnosis of tuberculous meningitis.
PMID- 10189293
TI - Clinical problem-solving: diagnosis of tuberculous meningitis.
PMID- 10189294
TI - Case 27-1998: eosinophilic cystitis.
PMID- 10189295
TI - Prenatal screening for open neural-tube defects in Maine.
PMID- 10189296
TI - Publication rate for articles presented at the Society for Pediatric Radiology.
PMID- 10189297
TI - Potential infections related to anabolic steroid injection in young adolescents.
PMID- 10189298
TI - Polio vaccine and polio.
PMID- 10189299
TI - Polio vaccine and polio.
PMID- 10189300
TI - To spank or not to spank.
PMID- 10189301
TI - To spank or not to spank.
PMID- 10189302
TI - Effectiveness of RSV-IVIG in premature infants: success in the home.
PMID- 10189303
TI - Length of stay, jaundice, and the hospital readmission.
PMID- 10189304
TI - Circulating thrombopoietin levels in a neonate with osteopetrosis.
PMID- 10189305
TI - 1997 AAP guidelines for prevention of early-onset group B streptococcal disease.
PMID- 10189306
TI - [Synthesis of lipophilic keto acids by acylation of alkylbenzenes as potential
inhibitors of phospholipase A2].
PMID- 10189307
TI - Swimming against the tide.
PMID- 10189308
TI - [Misoprostol: the solution is not so easy].
PMID- 10189309
TI - NIH weighs bold plan for online preprint publishing.
PMID- 10189310
TI - Bioprospecting. Model Indian deal generates payments.
PMID- 10189312
TI - Memory for order found in the motor cortex.
PMID- 10189311
TI - New findings reveal how legs take wing.
PMID- 10189313
TI - Engineering metabolism for commercial gains.
PMID- 10189314
TI - DNA: uncooked, al dente, or scotti?
PMID- 10189315
TI - Journal prices.
PMID- 10189316
TI - Breast implant safety.
PMID- 10189317
TI - IRB review and consent in human tissue research.
PMID- 10189318
TI - Unmasking a cheating gene.
PMID- 10189319
TI - Martin Rodbell (1925-1998).
PMID- 10189320
TI - Watching DNA at work.
PMID- 10189321
TI - Ultrastructural changes in fish gills as biomarker to assess small stream
pollution.
AB - In order to verify the principal suitability of gill ultrastructure as a
biomarker, semi-field studies with two endigoneous fish, trout (Salmo trutta f.
fario) and loach (Barbatula barbatula), were performed. The fish were exposed in
flow-through systems to one heavily polluted (Korsch) and one lightly polluted
small stream (Krahenbach) in South-West Germany. Ultrastructural responses in
gills were correlated with limnological and chemical data recorded over a 2 year
period in each stream. After 8 weeks of exposure to the heavily polluted stream,
fish showed ultrastructural changes in the gills, such as cell proliferation,
dilation of the endoplasmic reticulum, hyperplasia, hypersecretion, and
epithelial lifting in chloride, epithelial, and mucus cells. The results of the
study demonstrate that ultrastructural reactions in the gills of fish kept under
semi-field conditions are potentially useful biomarkers indicating small stream
pollution.
PMID- 10189322
TI - 3T3 cells have nuclear invaginations containing F-actin.
AB - Nuclear envelope invaginations occur in many kinds of cell. Double-labeling of
3T3 cells with Hoechst 33342 strain for DNA and phalloidin-rhodamine for F-actin,
show that some nuclei appear to contain tangled knots of F-actin. Concanavalin A
fluorescein staining for membranes shows that the knots are continuations of the
nuclear envelope. Although they contain F-actin, the knots appear by electron
microscopy to be cytoplasmic invaginations lacking microfilaments. Since we have
shown previously that nuclear-membrane associated actin forms perinuclear shells
in 3T3 cells, we propose that nuclear knots also are composed of actin associated
with the nuclear membrane. 3T3 nuclei also contain nuclear invaginations of a
second kind. These invaginations lie perpendicular to the first type and lack F
actin.
PMID- 10189323
TI - Use of hormone replacement therapy by postmenopausal women in the United States.
AB - BACKGROUND: The benefits and risks of hormone replacement therapy (HRT) in
postmenopausal women are not fully defined, and individual characteristics and
preferences may influence decisions to use this therapy. Previous studies of
postmenopausal women who use HRT have been conducted in local or highly selected
cohorts or have not focused on current use. OBJECTIVE: To examine
sociodemographic, clinical, and psychological factors associated with current use
of HRT in a national population-based cohort. DESIGN: Random-digit telephone
survey. SETTING: Probability sample of U.S. households with a telephone.
PARTICIPANTS: 495 postmenopausal women 50 to 74 years of age in 1995.
MEASUREMENTS: Current use of HRT. RESULTS: Current use of HRT was reported by
37.6% of women (58.7% of those who underwent hysterectomy and 19.6% of those who
did not undergo hysterectomy; P = 0.001). In multivariable analyses, use of HRT
was more common among women in the South (adjusted odds ratio, 2.67 [95% CI, 1.08
to 6.59]) and West (odds ratio, 2.76 [CI, 1.01 to 7.53]) than the Northeast. Use
was more common among college graduates (odds ratio, 3.72 [CI, 1.29 to 10.71])
and less common among women with diabetes mellitus (odds ratio, 0.17 [CI, 0.05 to
0.51]). Other cardiac risk factors and most psychological characteristics were
not associated with HRT use. CONCLUSIONS: Sociodemographic factors, such as
region and education, may be more strongly associated with use of HRT than
clinical factors, such as risk for cardiovascular disease. Future efforts should
focus on understanding sociodemographic variations, defining which women are most
likely to benefit, and targeting therapy to them.
PMID- 10189324
TI - The effect of dietary omega-3 fatty acids on coronary atherosclerosis. A
randomized, double-blind, placebo-controlled trial.
AB - BACKGROUND: Epidemiologic studies, studies of mechanisms of action, and many
animal studies indicate that dietary intake of omega-3 fatty acids has
antiatherosclerotic potential. Few trials in humans have examined this potential.
OBJECTIVE: To determine the effect of dietary intake of omega-3 fatty acids on
the course of coronary artery atherosclerosis in humans. DESIGN: Randomized,
double-blind, placebo-controlled, clinically controlled trial. SETTING:
University preventive cardiology unit. PATIENTS: 223 patients with
angiographically proven coronary artery disease. INTERVENTION: Fish oil
concentrate (55% eicosapentaenoic and docosahexaenoic acids) or a placebo with a
fatty acid composition resembling that of the average European diet, 6 g/d for 3
months and then 3 g/d for 21 months. MEASUREMENTS: The results of standardized
coronary angiography, done before and after 2 years of treatment, were evaluated
by an expert panel (primary end point) and by quantitative coronary angiography.
Patients were followed for clinical and laboratory status. RESULTS: Pairs of
angiograms (one taken at baseline and one taken at 2 years) were evaluated for 80
of 112 placebo recipients and 82 of 111 fish oil recipients. At the end of
treatment, 48 coronary segments in the placebo group showed changes (36 showed
mild progression, 5 showed moderate progression, and 7 showed mild regression)
and 55 coronary segments in the fish oil group showed changes (35 showed mild
progression, 4 showed moderate progression, 14 showed mild regression, and 2
showed moderate regression) (P = 0.041). Loss in minimal luminal diameter, as
assessed by quantitative coronary angiography, was somewhat less in the fish oil
group (P > 0.1). Fish oil recipients had fewer cardiovascular events (P = 0.10);
other clinical variables did not differ between the study groups. Low-density
lipoprotein cholesterol levels tended to be greater in the fish oil group.
CONCLUSION: Dietary intake of omega-3 fatty acids modestly mitigates the course
of coronary atherosclerosis in humans.
PMID- 10189325
TI - Depressive symptoms and 3-year mortality in older hospitalized medical patients.
AB - BACKGROUND: Depressive symptoms are common in hospitalized older persons.
However, their relation to long-term mortality is unclear because few studies
have rigorously considered potential confounders of the relation between
depression and mortality, such as comorbid illness, functional impairment, and
cognitive impairment. OBJECTIVE: To measure the association between depressive
symptoms and long-term mortality in hospitalized older persons. DESIGN:
Prospective cohort study. SETTING: General medical service of a teaching
hospital. PATIENTS: 573 patients 70 years of age or older. MEASUREMENTS:
Depressive symptoms (Geriatric Depression Scale score), severity of acute illness
(Acute Physiology and Chronic Health Evaluation II score), burden of comorbid
illness (Charlson comorbidity index score), physical function (a nurse assessed
dependence in six activities of daily living), and cognitive function (modified
Mini-Mental State Examination) were measured at hospital admission. Mortality
over the 3 years after admission was determined from the National Death Index.
Mortality rates among patients with six or more depressive symptoms were compared
with those among patients with five or fewer symptoms. RESULTS: The mean age of
the patients was 80 years; 68% of patients were women. Patients with six or more
depressive symptoms had greater comorbid illness, functional impairment, and
cognitive impairment at admission than patients with fewer depressive symptoms.
Three-year mortality was higher in patients with six or more depressive symptoms
(56% compared with 40%; hazard ratio, 1.56 [95% CI, 1.22 to 2.00]; P < 0.001).
After adjustment for age, acute illness severity, comorbid illness, functional
impairment, and cognitive impairment at the time of admission, patients with six
or more depressive symptoms continued to have a higher mortality rate during the
3 years after admission (hazard ratio, 1.34 [CI, 1.03 to 1.73]). Although
depressive symptoms contributed less to the mortality rate than did the total
burden of comorbid medical illnesses, the excess mortality rate associated with
depressive symptoms was greater than that conferred by one additional comorbid
medical condition. CONCLUSIONS: Depressive symptoms are associated with long-term
mortality in older patients hospitalized with medical illnesses. This association
is not fully explained by greater levels of comorbid illness, functional
impairment, and cognitive impairment in patients with more depressive symptoms.
PMID- 10189326
TI - Relations among CD4 lymphocyte count nadir, antiretroviral therapy, and HIV-1
disease progression: results from the EuroSIDA study.
AB - BACKGROUND: The effect of previous CD4 cell count nadir on clinical progression
in patients with increases in CD4 cell counts has not been investigated.
OBJECTIVE: To assess risk for progression of HIV disease in patients with CD4
counts of at least 200 cells/mm3 (stratified by the lowest previous CD4 count)
and compare the rate of progression in patients with CD4 counts less than 50
cells/mm3 with that in patients whose CD4 counts rebounded from less than 50
cells/mm3 to at least 200 cells/mm3. DESIGN: Prospective, observational
multicenter study. SETTING: 52 HIV outpatient clinics in Europe. PATIENTS: Two
groups were identified: those with CD4 counts of at least 200 cells/mm3 (group A)
and those with CD4 counts less than 50 cells/mm3 (group B). Group A was
stratified according to the lowest previous CD4 count: at least 150 cells/mm3
(stratum 1), 100 to 149 cells/mm3 (stratum 2), 50 to 99 cells/mm3 (stratum 3),
and 1 to 50 cells/mm3 (stratum 4). MEASUREMENTS: Patients were followed until a
progression event occurred (first AIDS-defining event, new AIDS-defining event,
or death) or until the CD4 count decreased to less than 200 cells/mm3 (group A)
or increased to more than 50 cells/mm3 (group B). Incidence rates were based on a
patient-years analysis and reported as events per 100 patient-years of follow-up;
the relative hazards for progression were based on Cox proportional hazards
models. RESULTS: The overall rate of disease progression in group A was 3.9 per
100 patient-years (95% CI, 3.5 to 4.3 per 100 patient-years), whereas in group B
it was much higher (72.9 per 100 patient-years [CI, 69.0 to 76.8 per 100 patient
years]). In group A, the rate increased in patients with previous low CD4 cell
count nadirs, resulting in a significant increase in the relative hazard for
progression. The relative hazards for strata 2, 3, and 4 were 2.29 (CI, 1.30 to
4.03), 3.65 (CI, 1.94 to 6.85), and 2.94 (CI, 1.44 to 6.00), respectively.
CONCLUSIONS: Increases in CD4 counts from very low levels to at least 200
cells/mm3 are associated with a much reduced rate of disease progression.
However, a previously low CD4 cell count nadir remains associated with a
moderately higher risk for disease progression among patients with CD4 counts of
at least 200 cells/mm3.
PMID- 10189327
TI - Arterial endothelial dysfunction related to passive smoking is potentially
reversible in healthy young adults.
AB - BACKGROUND: Passive smoking is associated with early arterial damage, but the
potential for reversibility of this damage is unknown. OBJECTIVE: To assess the
reversibility of arterial endothelial dysfunction, a key marker of early
atherosclerosis. DESIGN: Cross-sectional study. SETTING: Academic medical center.
PARTICIPANTS: 60 healthy persons 15 to 39 years of age: 20 with no exposure to
active or passive smoking, 20 nonsmoking passive smokers (exposure to
environmental tobacco smoke for > or = 1 hour per day for > or = 2 years), and 20
former passive smokers. MEASUREMENTS: Arterial endothelial function measured by
noninvasive ultrasonography. RESULTS: Endothelium-dependent dilatation was
significantly better in former passive smokers (5.1% +/- 4.1% [range, -1.2% to
15.6%]) than in current passive smokers (2.3% +/- 2.1% [range, -0.2% to 6.7%]) (P
= 0.01), although both groups were significantly impaired compared with
nonsmoking controls (8.9% +/- 3.2% [range, 2.1% to 16.7%]) (P < or = 0.01 for
both comparisons). CONCLUSIONS: In healthy young adults, arterial endothelial
dysfunction related to passive smoking seems to be partially reversible.
PMID- 10189328
TI - Cardiac asystole and bradycardia as a manifestation of left temporal lobe complex
partial seizure.
PMID- 10189329
TI - Acute heroin overdose.
AB - Acute heroin overdose is a common daily experience in the urban and suburban
United States and accounts for many preventable deaths. Heroin acts as a pro-drug
that allows rapid and complete central nervous system absorption; this accounts
for the drug's euphoric and toxic effects. The heroin overdose syndrome
(sensitivity for diagnosing heroin overdose, 92%; specificity, 76%) consists of
abnormal mental status, substantially decreased respiration, and miotic pupils.
The response of naloxone does not improve the sensitivity of this diagnosis. Most
overdoses occur at home in the company of others and are more common in the
setting of other drugs. Heroin-related deaths are strongly associated with use of
alcohol or other drugs. Patients with clinically significant respiratory
compromise need treatment, which includes airway management and intravenous or
subcutaneous naloxone. Hospital observation for several hours is necessary for
recurrence of hypoventilation or other complications. About 3% to 7% of treated
patients require hospital admission for pneumonia, noncardiogenic pulmonary
edema, or other complications. Methadone maintenance is an effective preventive
measure, and others strategies should be studied.
PMID- 10189330
TI - An inherited disorder of lymphocyte apoptosis: the autoimmune lymphoproliferative
syndrome.
AB - The autoimmune lymphoproliferative syndrome (ALPS) affords novel insights into
the mechanisms that regulate lymphocyte homeostasis and underlie the development
of autoimmunity. This syndrome arises early in childhood in persons who inherit
mutations in genes that mediate apoptosis, or programmed cell death. The timely
deletion of lymphocytes is a way to prevent their accumulation and the
persistence of cells that can react against the body's own antigens. In ALPS,
defective lymphocyte apoptosis permits chronic, nonmalignant adenopathy and
splenomegaly; the survival of normally uncommon "double-negative" CD3+ CD4- CD8-
T cells; and the development of autoimmune disease. Most cases of ALPS involve
heterozygous mutations in the lymphocyte surface protein Fas that impair a major
apoptotic pathway. Detailed immunologic investigations of the cellular and
cytokine profiles in ALPS show a prominent skewing toward a T-helper 2 phenotype;
this provides a rational explanation for the humoral autoimmunity typical of
patients with ALPS. Prospective evaluations of 26 patients and their families
show an ever-expanding spectrum of ALPS and its major complications:
hypersplenism, autoimmune hemolytic anemia, thrombocytopenia, and neutropenia.
Defective apoptosis may also contribute to a heightened risk for lymphoma.
PMID- 10189331
TI - Medical uncertainty and practice variation get personal: what should I do about
hormone replacement therapy?
PMID- 10189332
TI - Probability at the bedside: the knowing of chances or the chances of knowing?
PMID- 10189333
TI - Increasing organ donation in the African-American community: altruism in the face
of an untrustworthy system.
PMID- 10189334
TI - A good pair of hands.
PMID- 10189335
TI - Features and outcomes of classic heat stroke.
PMID- 10189336
TI - Features and outcomes of classic heat stroke.
PMID- 10189337
TI - Features and outcomes of classic heat stroke.
PMID- 10189338
TI - Features and outcomes of classic heat stroke.
PMID- 10189339
TI - Flock worker's lung.
PMID- 10189340
TI - Flock worker's lung.
PMID- 10189341
TI - Flock worker's lung.
PMID- 10189342
TI - Secrecy in science: the flock worker's lung investigation.
PMID- 10189343
TI - Increasing stair use.
PMID- 10189344
TI - Skin biopsies, cutaneous disease, and primary care.
PMID- 10189345
TI - Talking about treatment: the language of populations and the language of
individuals.
PMID- 10189346
TI - Your curriculum vitae is a snapshot of you.
PMID- 10189347
TI - Recommended practices for standard and the transmission-based precautions in the
perioperative practice setting. Association of Operating Room Nurses.
PMID- 10189348
TI - Searching for volunteer opportunities; hints for group e-mail.
PMID- 10189349
TI - Using secondary data analysis for nursing research.
PMID- 10189350
TI - Prevention of cardiac hypertrophy by calcineurin inhibition: hope or hype?
PMID- 10189351
TI - Signaling in myocardial hypertrophy: life after calcineurin?
PMID- 10189352
TI - Reversal of GATA-6 downregulation promotes smooth muscle differentiation and
inhibits intimal hyperplasia in balloon-injured rat carotid artery.
AB - The GATA-6 transcription factor is expressed in quiescent vascular smooth muscle
cells (VSMCs) in culture, and levels of its transcript are rapidly downregulated
on mitogen stimulation. In this study, we demonstrate that the GATA-6 transcript,
protein, and DNA-binding activity are downregulated in rat carotid arteries on
balloon injury. Downregulation was detected at 1 and 3 days after injury and
recovered by 7 days. To assess the role of GATA-6 downregulation in injury
induced vascular lesion formation, adenoviral vectors were used to express wild
type human GATA-6 cDNA (Ad-GATA6) or an inactive mutant cDNA that lacks a portion
of the zinc-finger domain (Ad-GATA6DeltaZF). Adenovirus-mediated GATA-6 gene
transfer to the vessel wall after balloon injury partially restored the levels of
GATA-6 protein and DNA-binding activity to before injury levels. The local
delivery of Ad-GATA6 but not Ad-GATA6DeltaZF inhibited lesion formation by 46%
relative to saline control and 50% relative to a control adenovirus that
expressed lacZ. Local delivery of Ad-GATA6 also reversed changes in the
expression patterns of smooth muscle myosin heavy chain, smooth muscle alpha
actin, calponin, vinculin, metavinculin, and proliferating cell nuclear antigen
that are associated with injury-induced VSMC phenotypic modulation. These data
indicate that the injury-induced downregulation of GATA-6 is an essential feature
of VSMC phenotypic modulation that contributes to vessel lesion formation.
PMID- 10189353
TI - Nitric oxide and C-type atrial natriuretic peptide stimulate primary aortic
smooth muscle cell migration via a cGMP-dependent mechanism: relationship to
microfilament dissociation and altered cell morphology.
AB - Migration of aortic smooth muscle cells is thought to be of essential importance
in vascular restenosis, remodeling, and angiogenesis. Recent studies have shown
that NO donors inhibit the migration of subcultured aortic smooth muscle cells.
However, there is evidence that NO elicits opposite effects on cell proliferation
in primary versus subcultured cells, indicating fundamental differences among
different models of aortic smooth muscle cell cultures. The purpose of the
current study was to investigate the effect of NO donors on migration of primary
cultures of rat aortic smooth muscle cells and to compare and contrast their
response with those in subcultured cells. A second purpose was to investigate
some of the underlying mechanisms associated with NO-induced effects on cell
migration. We report that 2 NO donors, S-nitroso-N-acetylpenicillamine (SNAP) and
2, 2-(hydroxynitrosohydrazino)bis-ethanamine, stimulated the migration of primary
cells in a wounded-culture model as well as in a transwell migration model. The
effect of NO donors was mimicked by 2 cGMP analogues and C-type natriuretic
peptide and blocked by a specific inhibitor of guanyl cyclase, 1H
(1,2,4)oxadiazolo[4,3, -a]quinoxalin-1-one, indicating the involvement of cGMP as
second messenger. Moreover, neither NO donors nor cGMP analogues altered
migration of primary cultures stimulated by either FBS or angiotensin II. In
contrast to its effect in primary cultures, SNAP did not alter basal or
stimulated migration of subcultured cells, except at a relatively high
concentration of 1 mmol/L, at which migration was inhibited. The migration
stimulatory effect of NO donors and cGMP was associated with altered cell
morphology and dissociation of actin filaments, consistent with recent studies
indicating that cell morphology and cytoskeletal organization influence cell
migration. The results suggest the possible involvement of NO-induced cell
migration in vascular injury or remodeling, representing conditions in which
vascular NO levels would be expected to be elevated.
PMID- 10189354
TI - Nuclear factor-kappa B regulates induction of apoptosis and inhibitor of
apoptosis protein-1 expression in vascular smooth muscle cells.
AB - Apoptosis is important in normal development as well as in diseases such as
atherosclerosis. However, the regulation of apoptosis is still not completely
understood. We now show that the transcription factor nuclear factor-kappaB (NF
kappaB) controls the induction of apoptosis in human and rat vascular smooth
muscle cells (SMCs). SMCs in high-density culture exhibited a high NF-kappaB
activity and were insensitive to induction of apoptosis. Inhibition of NF-kappaB
by adenovirus-mediated overexpression of its inhibitor IkappaBalpha caused a
marked increase in cell death at low but not high cell density. Elevating
endogenous IkappaBalpha levels by inhibiting its degradation with proteasomal
inhibitors resulted in induction of apoptosis in low-density SMCs, as detected by
increased binding of annexin V, reduced mitochondrial membrane potential, and
increased hypodiploid DNA. In high-density cultures, protection against apoptosis
was associated with the expression of inhibitor of apoptosis protein-1 (IAP-1).
Transfer of IkappaBalpha reduced human IAP-1 mRNA levels, which suggested that
IAP-1 is transcriptionally regulated by NF-kappaB. This was confirmed through
identification of a motif with NF-kappaB-like binding activity in the human IAP-1
promoter region. Moreover, antisense inhibition of IAP-1 sensitized high-density
SMCs to the induction of cell death. Together, our data imply that SMCs at high
density are protected by an antiapoptotic mechanism that involves increased
expression of NF-kappaB and IAP-1. Interference with pathways that control the
susceptibility to programmed cell death may be helpful in the treatment of
diseases where dysregulation of apoptosis is involved, eg, atherosclerosis and
restenosis.
PMID- 10189355
TI - Rapid induction and translocation of Egr-1 in response to mechanical strain in
vascular smooth muscle cells.
AB - The effect of mechanical strain on transcription and expression of the immediate
early genes, early growth response gene-1 (Egr-1), c-jun, and c-fos, was
investigated in neonatal rat aortic vascular smooth muscle (VSM) cells. Cells
grown on silicone elastomer plates were subjected to cyclic mechanical strain (1
Hz) at various durations and magnitudes. Egr-1 mRNA increased rapidly in response
to cyclic strain, reached a maximum of 10-fold after 30 minutes, and returned to
baseline after 4 hours. c-jun exhibited a similar pattern, whereas c-fos mRNA
expression was unaffected by strain. Cycloheximide prolonged the increase in Egr
1 and c-jun mRNA and caused superinduction of both. The threshold level of
continuous cyclic strain needed to induce expression was 5% for Egr-1 and c-jun.
Even a single cycle of mechanical strain that lasted 1 second was sufficient to
induce Egr-1 and c-jun mRNA. Strain also increased expression of a transiently
transfected Egr-1 promoter-reporter construct. The effect of varying
extracellular matrices on strain-induced Egr-1 and c-jun mRNA was examined. In
contrast to collagen type 1- and pronectin-coated plates, strain did not
significantly alter expression of Egr-1 and c-jun was less induced on laminin
coated plates. On collagen type 1, strain increased Egr-1 protein levels by 2.1
fold at 60 minutes. Immunofluorescence microscopy revealed translocation of Egr-1
to the nucleus in response to strain. These observations indicate that Egr-1
expression and translocation are sensitive to mechanical perturbation of the
cell. c-jun is also induced by strain, but c-fos is not. The signal for this
induction may involve specific cell-matrix interactions.
PMID- 10189356
TI - Identification of endothelial cell binding sites on the laminin gamma 1 chain.
AB - The laminins belong to a family of trimeric basement membrane glycoproteins with
multiple domains, structures, and functions. Endothelial cells bind laminin-1 and
form capillary-like structures when plated on a laminin-1-rich basement membrane
matrix, Matrigel. Laminin-1 is composed of 3 chains, alpha1, beta1, and gamma1.
Because laminin-1 is known to contain multiple biologically active sites, we have
screened 156 synthetic overlapping peptides spanning the entire laminin gamma1
chain for potential angiogenic sequences. Only 7 of these peptides, designated as
C16, C25, C30, C38, C64, C75, and C102, disrupted the formation of capillary-like
structures by human umbilical vein endothelial cells on Matrigel. Dose-response
experiments in the presence of 50 to 200 microg/mL showed that tube formation was
prevented by most peptides at 150 and 200 microg/mL, except for C16, which showed
strong activity at all concentrations. Active peptides promoted vessel sprouting
from aorta rings and angiogenesis in the chick chorioallantoic membrane assay. In
addition, the active peptides also promoted endothelial cell adhesion to dishes
coated with 0.1 microg of peptide and inhibited attachment to laminin-1 but not
to plastic or fibronectin. Four of the active peptides, C25, C38, C75, and C102,
may have cell-type specificity with endothelial cells, since they did not promote
PC12 neurite outgrowth or adhesion of B16-F10 melanoma and human submandibular
gland cells. These results suggest that specific laminin gamma1-chain peptides
have angiogenic activity with potential therapeutic applications.
PMID- 10189357
TI - Angiotensin II induces interleukin-6 transcription in vascular smooth muscle
cells through pleiotropic activation of nuclear factor-kappa B transcription
factors.
AB - Interleukin-6 (IL-6) is a multifunctional cytokine expressed by angiotensin II
(Ang II)-stimulated vascular smooth muscle cells (VSMCs) that functions as an
autocrine growth factor. In this study, we analyze the mechanism for Ang II
inducible IL-6 expression in quiescent rat VSMCs. Stimulation with the Ang II
agonist Sar1 Ang II (100 nmol/L) induced transcriptional expression of IL-6 mRNA
transcripts of 1.8 and 2.4 kb. In transient transfection assays of IL-6
promoter/luciferase reporter plasmids, Sar1 Ang II treatment induced IL-6
transcription in a manner completely dependent on the nuclear factor-kappaB (NF
kappaB) motif. Sar1 Ang II induced cytoplasmic-to-nuclear translocation of the NF
kappaB subunits Rel A and NF-kappaB1 with parallel changes in DNA-binding
activity in a biphasic manner, which produced an early peak at 15 minutes
followed by a nadir 1 to 6 hours later and a later peak at 24 hours. The early
phase of NF-kappaB translocation was dependent on weak simultaneous proteolysis
of the IkappaBalpha and beta inhibitors, whereas later translocation was
associated with enhanced processing of the p105 precursor into the mature 50-kDa
NF-kappaB1 form. Pretreatment with a potent inhibitor of IkappaBalpha
proteolysis, TPCK, completely blocked Sar1 Ang IIAng II-induced NF-kappaB
activation and induction of endogenous IL-6 gene expression, which indicated the
essential role of NF-kappaB in mediating IL-6 expression. We conclude that Ang II
is a pleiotropic regulator of the NF-kappaB transcription factor family and may
be responsible for activating the expression of cytokine gene networks in VSMCs.
PMID- 10189358
TI - Viral myocarditis: identification of five differentially expressed genes in
coxsackievirus B3-infected mouse heart.
AB - Differences in host susceptibility to viral myocarditis caused by a given strain
of coxsackievirus B3 (CVB3) are known to be largely related to host genetic
factors. Little is known, however, about the key genes that encode determinants
(mediators) of myocarditis development or the nature of injury. To identify these
genes and further understand the molecular mechanisms of the disease process, we
have used a murine model and the differential display technique to fingerprint
mRNAs from CVB3-infected mouse hearts. Total RNA was extracted from hearts of 4-
and 10-week-old A/J(H-2(a)) mice at day 4 after CVB3 infection, and mRNAs were
detected by reverse transcriptase-polymerase chain reaction and subsequently
analyzed on polyacrylamide DNA sequencing gels. The differentially displayed
bands were confirmed by Northern hybridization using the bands as cDNA probes.
Twenty-eight upregulated or downregulated bands were selected from the sequencing
gels; among these, 2 upregulated and 3 downregulated cDNA fragments were
confirmed by Northern hybridization. DNA sequence analysis and GenBank searching
have determined that 4 of the 5 candidate genes are homologous to genes encoding
Mus musculus inducible GTPase, mouse mitochondrial hydrophobic peptide (a subunit
of NADH dehydrogenase), mouse beta-globin, and Homo sapiens cAMP-regulated
response element binding protein (CREB) binding protein (CBP), respectively. The
remaining candidate gene matches an unpublished cDNA clone, M musculus Nip21 mRNA
(GenBank accession number, AF035207), which is homologous to human Nip2, a Bcl-2
binding protein. Our data suggest preliminarily that both structural and
nonstructural genes are involved in myocarditis development. For the structural
gene, beta-globin, we further confirmed its downregulation at the protein level
by measuring the mean cell volume of red blood cells and found it was marginally
reduced in the CVB3-infected group (P<0.06), with no change in hemoglobin
concentration. Cardiac myoglobin concentration was also measured and found to be
decreased (P<0.005), with a parallel decrease in total soluble protein in the
CVB3-infected mouse myocardium (P<0.01). We also noted that the ratio of
myoglobin to total protein was not significantly changed; this may be due to the
downregulation of additional genes in the host heart, a number being observed on
the differential display gels. The significant downregulation of beta-globin
major gene expression in the heart may be relevant to impaired cardiac function
in both the early and late postinfection period. The other identified
nonstructural genes are known to be involved in regulation of gene expression,
signal transduction pathways, and apoptotic cell death. The altered expression of
structural and nonstructural genes may play important roles in the mediation of
myocarditis development and perhaps other pathological processes in the heart.
PMID- 10189359
TI - Identification and expression of delta-isoforms of the multifunctional
Ca2+/calmodulin-dependent protein kinase in failing and nonfailing human
myocardium.
AB - Despite its importance for the regulation of heart function, little is known
about the isoform expression of the multifunctional Ca2+/calmodulin-dependent
protein kinase (CaMKII) in human myocardium. In this study, we investigated the
spectrum of CaMKII isoforms delta2, delta3, delta4, delta8, and delta9 in human
striated muscle tissue. Isoform delta3 is characteristically expressed in cardiac
muscle. In skeletal muscle, specific expression of a new isoform termed delta11
is demonstrated. Complete sequencing of human delta2 cDNA, representing all
common features of the investigated CaMKII subclass, revealed its high homology
to the corresponding rat cDNA. Comparative semiquantitative reverse transcription
polymerase chain reaction analyses from left ventricular tissues of normal hearts
and from patients suffering from dilated cardiomyopathy showed a significant
increase in transcript levels of isoform delta3 relative to the expression of
glyceraldehyde-3-phosphate dehydrogenase in diseased hearts (101. 6+/-11.0%
versus 64.9+/-9.9% in the nonfailing group; P<0.05, n=6). Transcript levels of
the other investigated cardiac CaMKII isoforms remained unchanged. At the protein
level, by using a subclass-specific antibody, we observed a similar increase of a
delta-CaMKII-specific signal (7.2+/-1.0 versus 3.8+/-0.7 optical density units in
the nonfailing group; P<0.05, n=4 through 6). The diseased state of the failing
hearts was confirmed by a significant increase in transcript levels for atrial
natriuretic peptide (292. 9+/-76.4% versus 40.1+/-3.2% in the nonfailing group;
P<0.05, n=3 through 6). Our data characterize for the first time the delta-CaMKII
isoform expression pattern in human hearts and demonstrate changes in this
expression pattern in heart failure.
PMID- 10189360
TI - Failure of calcineurin inhibitors to prevent pressure-overload left ventricular
hypertrophy in rats.
AB - A rapidly emerging body of literature implicates a pivotal role for the Ca2+
calmodulin-dependent phosphatase calcineurin as a cellular target for a variety
of Ca2+-dependent signaling pathways culminating in left ventricular hypertrophy
(LVH). Most of the recent experimental support for this hypothesis is derived
from in vitro studies or in vivo studies in transgenic mice expressing activated
calcineurin or mutant sarcomeric proteins. The aim of the present study was to
test whether calcineurin inhibitors, cyclosporin A (CsA) and FK 506, prevent
pressure-overload LVH using 2 standard rat models: (1) the spontaneously
hypertensive rat (SHR) and (2) aortic banding. The major new findings are 2-fold.
First, in SHR, LVH (left ventricular weight to body weight ratio) was unaffected
by a dose of CsA (5 mg. kg-1. d-1) that was sufficient to raise blood pressure
and to inhibit calcineurin-mediated transcriptional activation in skeletal
muscle. Second, in rats with aortic banding, LVH was unaffected by FK 506 (0.3
mg. kg-1. d-1) or even higher doses of CsA (10 and 20 mg. kg-1. d-1) that were
sufficient to inhibit 90% of total calcineurin phosphatase activity in the
hypertrophied myocardium. In the latter experiments, CsA blocked neither the
elevated left ventricular end-diastolic pressures, a measure of diastolic
function, nor the induction in atrial natriuretic peptide mRNA in the
hypertrophic ventricles. Thus, in numerous experiments, systemic administration
of potent calcineurin inhibitors did not prevent the development of LVH in 2
classic models of pressure-overload hypertrophy. These results demonstrate that
pressure-overload hypertrophy can arise through calcineurin-independent pathways.
PMID- 10189361
TI - Pressure overload induces severe hypertrophy in mice treated with cyclosporine,
an inhibitor of calcineurin.
AB - Cardiac hypertrophy is the fundamental adaptation of the adult heart to
mechanical load. Recent work has shown that inhibition of calcineurin activity
with cyclosporine suppresses the development of hypertrophy in calcineurin
transgenic mice and in in vitro systems of neonatal rat cardiocytes stimulated
with peptide growth factors. To test the hypothesis that the calcineurin
signaling pathway is critical for load-induced hypertrophy in vivo, we examined
the effects of cyclosporine treatment on left ventricular hypertrophy induced by
experimental ascending aortic stenosis for 4 weeks in mice. Left ventricular
systolic pressure was elevated to a similar level in aortic stenosis mice that
were treated with cyclosporine versus no drug. Left ventricular mass and myocyte
size were similar in treated and untreated aortic stenosis animals and
significantly greater than control animals, showing that cyclosporine treatment
does not suppress hypertrophic growth. Both treated and untreated animals showed
increased left ventricular expression of the load-sensitive gene atrial
natriuretic factor. Calcineurin activity was measured in the left ventricle and
the spleen from control mice and aortic stenosis mice treated with cyclosporine
versus no drug. Levels of calcineurin activity were similar in the spleens of
control and untreated aortic stenosis mice. However, calcineurin activity was
severely depressed in left ventricular tissue of untreated aortic stenosis mice
compared with control mice and was further reduced by cyclosporine treatment.
Thus, pathological hypertrophy and cardiac-restricted gene expression induced by
pressure overload in vivo are not suppressed by treatment with cyclosporine and
do not appear to depend on the elevation of left ventricular calcineurin
activity.
PMID- 10189362
TI - Cyclosporine attenuates pressure-overload hypertrophy in mice while enhancing
susceptibility to decompensation and heart failure.
AB - Left ventricular hypertrophy (LVH) is a compensatory mechanism to cope with
pressure overload. Recently, a calcineurin pathway mediating LVH and its
prevention by cyclosporine was reported. We examined whether calcineurin mediates
LVH due to pressure overload in mice. Pressure overload was induced by aortic
banding in 53 mice (32 treated with cyclosporine [25 mg. kg-1. d-1], 21 treated
with vehicle). There were 17 sham-operated mice (9 treated with vehicle, 8
treated with cyclosporine). At 3 weeks after surgery, LV weight to body weight
was greater in the nontreatment banded group (4.39+/-0. 16 mg/g) than in the
cyclosporine-treated banded group (3.95+/-0.14 mg/g, P<0.05), with both groups
being greater compared with the entire group of sham-operated mice (3.02+/-0.04
mg/g). The pressure gradient between the ascending and abdominal aorta was not
different between the cyclosporine-treated (49.6+/-6.1 mm Hg) and nontreatment
groups (48.7+/-4.6 mm Hg). Although LV systolic pressure was lower in the
cyclosporine-treated banded animals, LV systolic wall stress was similar in the
nontreatment banded group and in the cyclosporine-treated group. However, LV
dP/dt was lower (P=0.05) in the cyclosporine-treated banded group (4774+/-656 mm
Hg/s) than in the nontreatment banded group (6604+/-516 mm Hg/s). During the
protocol, 23 of 32 mice in the cyclosporine-treated group and 9 of 21 mice in the
nontreatment group died. All deaths occurred within 10 days after surgery. Deaths
caused by heart failure were 7.2-fold higher (P<0.05) in the cyclosporine-treated
group, whereas deaths due to other causes were not different between the 2
groups. In addition, LV function of mice was assessed at 48 hours after banding;
LV ejection fraction measured with echocardiography was lower (P<0.05) in the
cyclosporine-treated banded group (66+/-3.0%) than in the nontreatment banded
group (79+/-1.5%), whereas LV systolic wall stresses were similar. Calcineurin
phosphatase activity was depressed similarly in both cyclosporine-treated groups
compared with both nontreatment groups. Thus, cyclosporine could attenuate, but
not prevent, LVH at the expense of inhibiting an important compensatory mechanism
in response to pressure overload, resulting in reduced LV wall stress and
function and increased susceptibility to decompensation and heart failure.
PMID- 10189363
TI - Calcineurin inhibition as therapy for cardiac hypertrophy and heart failure:
requiescat in pace?
PMID- 10189364
TI - Evidence for a relatively random array of human chromosomes on the mitotic ring.
AB - We used fluorescence in situ hybridization (FISH) to study the positions of human
chromosomes on the mitotic rings of cultured human lymphocytes, MRC-5
fibroblasts, and CCD-34Lu fibroblasts. The homologous chromosomes of all three
cell types had relatively random positions with respect to each other on the
mitotic rings of prometaphase rosettes and anaphase cells. Also, the positions of
the X and Y chromosomes, colocalized with the somatic homologues in male cells,
were highly variable from one mitotic ring to another. Although random
chromosomal positions were found in different pairs of CCD-34Lu and MRC-5 late
anaphases, the separations between the same homologous chromosomes in paired late
anaphase and telophase chromosomal masses were highly correlated. Thus, although
some loose spatial associations of chromosomes secondary to interphase
positioning may exist on the mitotic rings of some cells, a fixed order of human
chromosomes and/or a rigorous separation of homologous chromosomes on the mitotic
ring are not necessary for normal mitosis. Furthermore, the relative chromosomal
positions on each individual metaphase plate are most likely carried through
anaphase into telophase.
PMID- 10189365
TI - Ctf19p: A novel kinetochore protein in Saccharomyces cerevisiae and a potential
link between the kinetochore and mitotic spindle.
AB - A genetic synthetic dosage lethality (SDL) screen using CTF13 encoding a known
kinetochore protein as the overexpressed reference gene identified two chromosome
transmission fidelity (ctf) mutants, YCTF58 and YCTF26. These mutant strains
carry independent alleles of a novel gene, which we have designated CTF19. In
light of its potential role in kinetochore function, we have cloned and
characterized the CTF19 gene in detail. CTF19 encodes a nonessential 369-amino
acid protein. ctf19 mutant strains display a severe chromosome missegregation
phenotype, are hypersensitive to benomyl, and accumulate at G2/M in cycling
cells. CTF19 genetically interacts with kinetochore structural mutants and
mitotic checkpoint mutants. In addition, ctf19 mutants show a defect in the
ability of centromeres on minichromosomes to bind microtubules in an in vitro
assay. In vivo cross-linking and chromatin immunoprecipitation demonstrates that
Ctf19p specifically interacts with CEN DNA. Furthermore, Ctf19-HAp localizes to
the nuclear face of the spindle pole body and genetically interacts with a
spindle-associated protein. We propose that Ctf19p is part of a macromolecular
kinetochore complex, which may function as a link between the kinetochore and the
mitotic spindle.
PMID- 10189366
TI - A nonerythroid isoform of protein 4.1R interacts with the nuclear mitotic
apparatus (NuMA) protein.
AB - Red blood cell protein 4.1 (4.1R) is an 80- kD erythrocyte phosphoprotein that
stabilizes the spectrin/actin cytoskeleton. In nonerythroid cells, multiple 4.1R
isoforms arise from a single gene by alternative splicing and predominantly code
for a 135-kD isoform. This isoform contains a 209 amino acid extension at its NH2
terminus (head piece; HP). Immunoreactive epitopes specific for HP have been
detected within the cell nucleus, nuclear matrix, centrosomes, and parts of the
mitotic apparatus in dividing cells. Using a yeast two-hybrid system, in vitro
binding assays, coimmunolocalization, and coimmunoprecipitation studies, we show
that a 135-kD 4.1R isoform specifically interacts with the nuclear mitotic
apparatus (NuMA) protein. NuMA and 4.1R partially colocalize in the interphase
nucleus of MDCK cells and redistribute to the spindle poles early in mitosis.
Protein 4.1R associates with NuMA in the interphase nucleus and forms a complex
with spindle pole organizing proteins, NuMA, dynein, and dynactin during cell
division. Overexpression of a 135-kD isoform of 4.1R alters the normal
distribution of NuMA in the interphase nucleus. The minimal sequence sufficient
for this interaction has been mapped to the amino acids encoded by exons 20 and
21 of 4.1R and residues 1788-1810 of NuMA. Our results not only suggest that 4.1R
could, possibly, play an important role in organizing the nuclear architecture,
mitotic spindle, and spindle poles, but also could define a novel role for its 22
24-kD domain.
PMID- 10189367
TI - Phosphorylation-dependent binding of hepatitis B virus core particles to the
nuclear pore complex.
AB - Although many viruses replicate in the nucleus, little is known about the
processes involved in the nuclear import of viral genomes. We show here that in
vitro generated core particles of human hepatitis B virus bind to nuclear pore
complexes (NPCs) in digitonin-permeabilized mammalian cells. This only occurred
if the cores contained phosphorylated core proteins. Binding was inhibited by
wheat germ agglutinin, by antinuclear pore complex antibodies, and by peptides
corresponding either to classical nuclear localization signals (NLS) or to COOH
terminal sequences of the core protein. Binding was dependent on the nuclear
transport factors importins (karyopherins) alpha and beta. The results suggested
that phosphorylation induces exposure of NLS in the COOH-terminal portion of the
core protein that allows core binding to the NPCs by the importin- (karyopherin-)
mediated pathway. Thus, phosphorylation of the core protein emerged as an
important step in the viral replication cycle necessary for transport of the
viral genome to the nucleus.
PMID- 10189368
TI - Early assembly step of a retroviral envelope glycoprotein: analysis using a
dominant negative assay.
AB - As for most integral membrane proteins, the intracellular transport of retroviral
envelope glycoproteins depends on proper folding and oligomeric assembly in the
ER. In this study, we considered the hypothesis that a panel of 22 transport
defective mutants of the human T cell leukemia virus type 1 envelope glycoprotein
might be defective in ER assembly. Upon cell cotransfection with wild-type
envelope, however, the vast majority of these transport-defective mutants (21 of
22) exerted a specific trans-dominant negative effect. This effect was due to
random dimerization of the mutated and wild-type glycoproteins that prevented the
intracellular transport of the latter. This unexpected result suggests that
association of glycoprotein monomers precedes the completion of folding. The only
mutation that impaired this early assembly was located at the NH2 terminus of the
protein. COOH-terminally truncated, soluble forms of the glycoprotein were also
trans-dominant negative provided that their NH2 terminus was intact. The leucine
zipper-like domain, although involved in oligomerization of the envelope
glycoproteins at the cell surface, did not contribute to their intracellular
assembly. We propose that, at a step subsequent to translation, but preceding
complete folding of the monomers, glycoproteins assemble via their NH2-terminal
domains, which, in turn, permits their cooperative folding.
PMID- 10189370
TI - GMAP-210, A cis-Golgi network-associated protein, is a minus end microtubule
binding protein.
AB - We report that a peripheral Golgi protein with a molecular mass of 210 kD
localized at the cis-Golgi network (Rios, R.M., A.M. Tassin, C. Celati, C.
Antony, M.C. Boissier, J.C. Homberg, and M. Bornens. 1994. J. Cell Biol. 125:997
1013) is a microtubule-binding protein that associates in situ with a
subpopulation of stable microtubules. Interaction of this protein, now called
GMAP-210, for Golgi microtubule-associated protein 210, with microtubules in
vitro is direct, tight and nucleotide-independent. Biochemical analysis further
suggests that GMAP-210 specifically binds to microtubule ends. The full-length
cDNA encoding GMAP-210 predicts a protein of 1, 979 amino acids with a very long
central coiled-coil domain. Deletion analyses in vitro show that the COOH
terminus of GMAP-210 binds to microtubules whereas the NH2 terminus binds to
Golgi membranes. Overexpression of GMAP-210-encoding cDNA induced a dramatic
enlargement of the Golgi apparatus and perturbations in the microtubule network.
These effects did not occur when a mutant lacking the COOH-terminal domain was
expressed. When transfected in fusion with the green fluorescent protein, the NH2
terminal domain associated with the cis-Golgi network whereas the COOH-terminal
microtubule-binding domain localized at the centrosome. Altogether these data
support the view that GMAP-210 serves to link the cis-Golgi network to the minus
ends of centrosome-nucleated microtubules. In addition, this interaction appears
essential for ensuring the proper morphology and size of the Golgi apparatus.
PMID- 10189371
TI - Inhibition of caspases inhibits the release of apoptotic bodies: Bcl-2 inhibits
the initiation of formation of apoptotic bodies in chemotherapeutic agent-induced
apoptosis.
AB - During apoptosis, the cell actively dismantles itself and reduces cell size by
the formation and pinching off of portions of cytoplasm and nucleus as "apoptotic
bodies." We have combined our previously established quantitative assay relating
the amount of release of [3H]-membrane lipid to the degree of apoptosis with
electron microscopy (EM) at a series of timepoints to study apoptosis of lymphoid
cells exposed to vincristine or etoposide. We find that the [3H]-membrane lipid
release assay correlates well with EM studies showing the formation and release
of apoptotic bodies and cell death, and both processes are regulated in parallel
by inducers or inhibitors of apoptosis. Overexpression of Bcl-2 or inhibition of
caspases by DEVD inhibited equally well the activation of caspases as indicated
by PARP cleavage. They also inhibited [3H]-membrane lipid release and release of
apoptotic bodies. EM showed that cells overexpressing Bcl-2 displayed near-normal
morphology and viability in response to vincristine or etoposide. In contrast,
DEVD did not prevent cell death. Although DEVD inhibited the chromatin
condensation, PARP cleavage, release of apoptotic bodies, and release of labeled
lipid, DEVD-treated cells showed accumulation of heterogeneous vesicles trapped
in the condensed cytoplasm. These results suggest that inhibition of caspases
arrested the maturation and release of apoptotic bodies. Our results also imply
that Bcl-2 regulates processes in addition to caspase activation.
PMID- 10189369
TI - Golgi structure correlates with transitional endoplasmic reticulum organization
in Pichia pastoris and Saccharomyces cerevisiae.
AB - Golgi stacks are often located near sites of "transitional ER" (tER), where COPII
transport vesicles are produced. This juxtaposition may indicate that Golgi
cisternae form at tER sites. To explore this idea, we examined two budding
yeasts: Pichia pastoris, which has coherent Golgi stacks, and Saccharomyces
cerevisiae, which has a dispersed Golgi. tER structures in the two yeasts were
visualized using fusions between green fluorescent protein and COPII coat
proteins. We also determined the localization of Sec12p, an ER membrane protein
that initiates the COPII vesicle assembly pathway. In P. pastoris, Golgi stacks
are adjacent to discrete tER sites that contain COPII coat proteins as well as
Sec12p. This arrangement of the tER-Golgi system is independent of microtubules.
In S. cerevisiae, COPII vesicles appear to be present throughout the cytoplasm
and Sec12p is distributed throughout the ER, indicating that COPII vesicles bud
from the entire ER network. We propose that P. pastoris has discrete tER sites
and therefore generates coherent Golgi stacks, whereas S. cerevisiae has a
delocalized tER and therefore generates a dispersed Golgi. These findings open
the way for a molecular genetic analysis of tER sites.
PMID- 10189372
TI - Direct observations of the mechanical behaviors of the cytoskeleton in living
fibroblasts.
AB - Cytoskeletal proteins tagged with green fluorescent protein were used to directly
visualize the mechanical role of the cytoskeleton in determining cell shape. Rat
embryo (REF 52) fibroblasts were deformed using glass needles either uncoated for
purely physical manipulations, or coated with laminin to induce attachment to the
cell surface. Cells responded to uncoated probes in accordance with a three-layer
model in which a highly elastic nucleus is surrounded by cytoplasmic microtubules
that behave as a jelly-like viscoelastic fluid. The third, outermost cortical
layer is an elastic shell under sustained tension. Adhesive, laminin-coated
needles caused focal recruitment of actin filaments to the contacted surface
region and increased the cortical layer stiffness. This direct visualization of
actin recruitment confirms a widely postulated model for mechanical connections
between extracellular matrix proteins and the actin cytoskeleton. Cells tethered
to laminin-treated needles strongly resisted elongation by actively contracting.
Whether using uncoated probes to apply simple deformations or laminin-coated
probes to induce surface-to-cytoskeleton interaction we observed that
experimentally applied forces produced exclusively local responses by both the
actin and microtubule cytoskeleton. This local accomodation and dissipation of
force is inconsistent with the proposal that cellular tensegrity determines cell
shape.
PMID- 10189373
TI - The receptor recycling pathway contains two distinct populations of early
endosomes with different sorting functions.
AB - Receptor recycling involves two endosome populations, peripheral early endosomes
and perinuclear recycling endosomes. In polarized epithelial cells, either or
both populations must be able to sort apical from basolateral proteins, returning
each to its appropriate plasma membrane domain. However, neither the roles of
early versus recycling endosomes in polarity nor their relationship to each other
has been quantitatively evaluated. Using a combined morphological, biochemical,
and kinetic approach, we found these two endosome populations to represent
physically and functionally distinct compartments. Early and recycling endosomes
were resolved on Optiprep gradients and shown to be differentially associated
with rab4, rab11, and transferrin receptor; rab4 was enriched on early endosomes
and at least partially depleted from recycling endosomes, with the opposite being
true for rab11 and transferrin receptor. The two populations were also
pharmacologically distinct, with AlF4 selectively blocking export of transferrin
receptor from recycling endosomes to the basolateral plasma membrane. We applied
these observations to a detailed kinetic analysis of transferrin and dimeric IgA
recycling and transcytosis. The data from these experiments permitted the
construction of a testable, mathematical model which enabled a dissection of the
roles of early and recycling endosomes in polarized receptor transport. Contrary
to expectations, the majority (>65%) of recycling to the basolateral surface is
likely to occur from early endosomes, but with relatively little sorting of
apical from basolateral proteins. Instead, more complete segregation of
basolateral receptors from receptors intended for transcytosis occurred upon
delivery to recycling endosomes.
PMID- 10189374
TI - The MAL proteolipid is necessary for normal apical transport and accurate sorting
of the influenza virus hemagglutinin in Madin-Darby canine kidney cells.
AB - The MAL (MAL/VIP17) proteolipid is a nonglycosylated integral membrane protein
expressed in a restricted pattern of cell types, including T lymphocytes, myelin
forming cells, and polarized epithelial cells. Transport of the influenza virus
hemagglutinin (HA) to the apical surface of epithelial Madin-Darby canine kidney
(MDCK) cells appears to be mediated by a pathway involving glycolipid- and
cholesterol- enriched membranes (GEMs). In MDCK cells, MAL has been proposed
previously as being an element of the protein machinery for the GEM-dependent
apical transport pathway. Using an antisense oligonucleotide-based strategy and a
newly generated monoclonal antibody to canine MAL, herein we have approached the
effect of MAL depletion on HA transport in MDCK cells. We have found that MAL
depletion diminishes the presence of HA in GEMs, reduces the rate of HA transport
to the cell surface, inhibits the delivery of HA to the apical surface, and
produces partial missorting of HA to the basolateral membrane. These effects were
corrected by ectopic expression of MAL in MDCK cells whose endogenous MAL protein
was depleted. Our results indicate that MAL is necessary for both normal apical
transport and accurate sorting of HA.
PMID- 10189375
TI - Membrane targeting and stabilization of sarcospan is mediated by the sarcoglycan
subcomplex.
AB - The dystrophin-glycoprotein complex (DGC) is a multisubunit complex that spans
the muscle plasma membrane and forms a link between the F-actin cytoskeleton and
the extracellular matrix. The proteins of the DGC are structurally organized into
distinct subcomplexes, and genetic mutations in many individual components are
manifested as muscular dystrophy. We recently identified a unique tetraspan-like
dystrophin-associated protein, which we have named sarcospan (SPN) for its
multiple sarcolemma spanning domains (Crosbie, R.H., J. Heighway, D.P. Venzke,
J.C. Lee, and K.P. Campbell. 1997. J. Biol. Chem. 272:31221-31224). To probe
molecular associations of SPN within the DGC, we investigated SPN expression in
normal muscle as a baseline for comparison to SPN's expression in animal models
of muscular dystrophy. We show that, in addition to its sarcolemma localization,
SPN is enriched at the myotendinous junction (MTJ) and neuromuscular junction
(NMJ), where it is a component of both the dystrophin- and utrophin-glycoprotein
complexes. We demonstrate that SPN is preferentially associated with the
sarcoglycan (SG) subcomplex, and this interaction is critical for stable
localization of SPN to the sarcolemma, NMJ, and MTJ. Our experiments indicate
that assembly of the SG subcomplex is a prerequisite for targeting SPN to the
sarcolemma. In addition, the SG- SPN subcomplex functions to stabilize alpha
dystroglycan to the muscle plasma membrane. Taken together, our data provide
important information about assembly and function of the SG-SPN subcomplex.
PMID- 10189377
TI - Integrin-regulated secretion of interleukin 4: A novel pathway of
mechanotransduction in human articular chondrocytes.
AB - Chondrocyte function is regulated partly by mechanical stimulation. Optimal
mechanical stimulation maintains articular cartilage integrity, whereas abnormal
mechanical stimulation results in development and progression of osteoarthritis
(OA). The responses of signal transduction pathways in human articular
chondrocytes (HAC) to mechanical stimuli remain unclear. Previous work has shown
the involvement of integrins and integrin-associated signaling pathways in
activation of plasma membrane apamin-sensitive Ca2+-activated K+ channels that
results in membrane hyperpolarization of HAC after 0. 33 Hz cyclical mechanical
stimulation. To further investigate mechanotransduction pathways in HAC and show
that the hyperpolarization response to mechanical stimulation is a result of an
integrin-dependent release of a transferable secreted factor, we used this
response. Neutralizing antibodies to interleukin 4 (IL-4) and IL-4 receptor alpha
inhibit mechanically induced membrane hyperpolarization and anti-IL-4 antibodies
neutralize the hyperpolarizing activity of medium from mechanically stimulated
cells. Antibodies to interleukin 1beta (IL-1beta) and cytokine receptors,
interleukin 1 receptor type I and the common gamma chain/CD132 (gamma) have no
effect on me- chanically induced membrane hyperpolarization. Chondrocytes from IL
4 knockout mice fail to show a membrane hyperpolarization response to cyclical
mechanical stimulation. Mechanically induced release of the chondroprotective
cytokine IL-4 from HAC with subsequent autocrine/paracrine activity is likely to
be an important regulatory pathway in the maintenance of articular cartilage
structure and function. Finally, dysfunction of this pathway may be implicated in
OA.
PMID- 10189378
TI - wing blister, a new Drosophila laminin alpha chain required for cell adhesion and
migration during embryonic and imaginal development.
AB - We report the molecular and functional characterization of a new alpha chain of
laminin in Drosophila. The new laminin chain appears to be the Drosophila
counterpart of both vertebrate alpha2 (also called merosin) and alpha1 chains,
with a slightly higher degree of homology to alpha2, suggesting that this chain
is an ancestral version of both alpha1 and alpha2 chains. During embryogenesis,
the protein is associated with basement membranes of the digestive system and
muscle attachment sites, and during larval stage it is found in a specific
pattern in wing and eye discs. The gene is assigned to a locus called wing
blister (wb), which is essential for embryonic viability. Embryonic phenotypes
include twisted germbands and fewer pericardial cells, resulting in gaps in the
presumptive heart and tracheal trunks, and myotubes detached from their target
muscle attachment sites. Most phenotypes are in common with those observed in
Drosophila laminin alpha3, 5 mutant embryos and many are in common with those
observed in integrin mutations. Adult phenotypes show blisters in the wings in
viable allelic combinations, similar to phenotypes observed in integrin genes.
Mutation analysis in the eye demonstrates a function in rhabdomere organization.
In summary, this new laminin alpha chain is essential for embryonic viability and
is involved in processes requiring cell migration and cell adhesion.
PMID- 10189379
TI - Targeted deletions created in yeast vectors by recombinational excision.
AB - We have developed a simple method for creating defined deletions in yeast vectors
by utilizing the ability of Saccharomyces cerevisiae to perform homologous
recombination. Two complementary single-stranded oligonucleotides are designed so
that the 5' and 3' halves of the resulting double-stranded oligonucleotide are
homologous to the 5' and 3' side of a desired deletion junction, respectively.
The sequence to be deleted is cleaved by restriction endonuclease digestion,
followed by co-transformation of the linearized plasmid and the oligonucleotide
into yeast. By homologous recombination in vivo, a subset of the plasmids will
recircularize and simultaneously acquire the deletion as defined by the
oligonucleotide.
PMID- 10189376
TI - Identification of a suppressor of the Dictyostelium profilin-minus phenotype as a
CD36/LIMP-II homologue.
AB - Profilin is an ubiquitous G-actin binding protein in eukaryotic cells. Lack of
both profilin isoforms in Dictyostelium discoideum resulted in impaired
cytokinesis and an arrest in development. A restriction enzyme-mediated
integration approach was applied to profilin-minus cells to identify suppressor
mutants for the developmental phenotype. A mutant with wild-type-like development
and restored cytokinesis was isolated. The gene affected was found to code for an
integral membrane glycoprotein of a predicted size of 88 kD containing two
transmembrane domains, one at the NH2 terminus and the other at the COOH
terminus. It is homologous to mammalian CD36/LIMP-II and represents the first
member of this family in D. discoideum, therefore the name DdLIMP is proposed.
Targeted disruption of the lmpA gene in the profilin-minus background also
rescued the mutant phenotype. Immunofluorescence revealed a localization in
vesicles and ringlike structures on the cell surface. Partially purified DdLIMP
bound specifically to PIP2 in sedimentation and gel filtration assays. A direct
interaction between DdLIMP and profilin could not be detected, and it is unclear
how far upstream in a regulatory cascade DdLIMP might be positioned. However, the
PIP2 binding of DdLIMP points towards a function via the phosphatidylinositol
pathway, a major regulator of profilin.
PMID- 10189380
TI - Hematology in china
PMID- 10189381
TI - Expression of the nlsLacz gene in dendritic cells derived from retrovirally
transduced peripheral blood CD34+ cells.
AB - BACKGROUND AND OBJECTIVE: Gene transfer and expression of exogenous genetic
information coding for an immunogenic protein in antigen presenting cells (APCs)
can promote an immune response. This was investigated by retroviral transfer of a
marker gene into CD34+ derived APCs. DESIGN AND METHODS: To achieve long term
expression of a specific transgene in APCs, G-CSF mobilized peripheral blood
CD34+ cell populations were retrovirally transduced with the bacterial nlsLacZ, a
marker gene used here as a model, in the presence of IL-3, IL-6, GM-CSF and SCF
prior to being induced to differentiate into dendritic and macrophage cells by GM
CSF and TNF-a. RESULTS: Addition of IL-4 was found to induce dendritic
differentiation preferentially by inhibiting proliferation and differentiation of
the macrophage lineage. As assessed by X-Gal staining, LacZ gene expression was
observed in cells from both the dendritic lineage (CD1a+/CD14-) which still
exhibits the highest immunostimulatory activity in mixed lymphocyte reaction and
from the macrophage lineage (CD1a-/ CD14+). INTERPRETATION AND CONCLUSIONS: This
study sets out the possibility of transducing dendritic and macrophage
progenitors present in the CD34+ cell population and in using a marker gene such
as nlsLacZ to study gene expression in antigen presenting cell compartments.
PMID- 10189382
TI - Simultaneous detection of FV Q506 and prothrombin 20210 A variation by allele
specific PCR.
AB - BACKGROUND AND OBJECTIVE: Factor V Leiden is the most important risk factor for
hereditary thromboembolism, whereas the mutation in the 3'-untranslated region of
the prothrombin gene seems to be only a mild risk factor for thrombotic events.
On the other hand the factor V mutation (Arg 506) is frequently coinherited with
the prothrombin 3'-untranslated region G20210A variant and there is increasing
evidence that the co-segregated prothrombin variant is an additional risk factor
for venous thromboembolism, contributing to thrombotic manifestations. A rapid,
simple and cost-effective screening method is, therefore, required for the
detection of both factor V Leiden and the prothrombin variant A20210G. DESIGN AND
METHODS: Eighty-eight patients were enrolled in this study. Forty-four had a
previously identified factor V and/or prothrombin mutation, the remaining 44
patients served as negative controls. A multiplex allele specific oligonucleotide
PCR was established for the simultaneous detection of the two genetic risk
factors for thrombophilia. To test the specificity of the simultaneous ASO PCR
approach, the mutated and physiological factor V and prothrombin amplification
products were sequenced. RESULTS: The factor V Leiden mutation and the
prothrombin variant were correctly identified in all of 44 patients with known
mutations. Furthermore the test was able to detect the mutated factor V and the
II variant alone, as well as in the cosegregated pattern. Five patients with a
homozygous pattern of factor V Leiden or prothrombin variant were also correctly
identified. The sensitivity of the test is therefore 100%. In none of the 44
control cases were false positive results seen. INTERPRETATION AND CONCLUSIONS:
The ASO PCR test is a rapid, simple and cost-effective screening test for
thrombophilia.
PMID- 10189383
TI - Clinico-biological implications of increased serum levels of interleukin-8 in B
cell chronic lymphocytic leukemia.
AB - BACKGROUND AND OBJECTIVE: Constitutive cellular expression and serum release of
biologically active interleukin-8 (IL-8) has been reported in B-cell chronic
lymphocytic leukemia (CLL). Given the autocrine role played by IL-8 in the
process of cell accumulation characteristic of this disease we tried to
investigate clinico-biological implications of increased serum levels of this
cytokine in an unselected series of B-cell CLL patients. DESIGN AND METHODS:
Serum levels of IL-8 were determined at the time of diagnosis in 58 previously
untreated B-CLL patients using an immunoenzyme assay. Results were correlated
with main clinico-hematologic features as well as with the risk of disease
progression. Finally, we looked for associations between IL-8 and molecules
directly involved in apoptosis, such as intracellular bcl-2 and soluble APO
1/Fas. RESULTS: Increased serum levels of IL-8 were found in 15 out of 58 (25.8%)
B-cell CLL patients. Serum levels of IL-8 did not reflect clinico-biological
features representative of tumor mass such as clinical stage, histopathologic
pattern of bone marrow (BM) involvement, b2-microglobulin, sCD23 and sCD27
titers. Interestingly, circulating levels of IL-8 paralleled those of
intracellular bcl-2 (r = 0.522; p = 0.01), thus confirming that the antiapoptotic
effect of IL-8 can be exerted through a bcl-2 dependent pathway. Levels of IL-8
did not match those of soluble Apo-1/Fas (r = -0.013; p = 0.943). Finally, stage
A patients with levels of IL-8 above the median value (i.e. 4.5 pg/mL) were more
likely to progress to a more advanced clinical stage than those with levels below
the median value (p < 0.05). INTERPRETATION AND CONCLUSIONS: IL-8 is an
interesting marker in B-cell CLL, closely involved in the pathogenesis of
disease. Furthermore, it is useful for predicting the pace of disease progression
in early clinical stages.
PMID- 10189384
TI - Evaluation of trisomy 12 by fluorescence in situ hybridization in peripheral
blood, bone marrow and lymph nodes of patients with B-cell chronic lymphocytic
leukemia.
AB - BACKGROUND AND OBJECTIVE: Trisomy 12 is the most common numerical chromosomal
aberration in patients with B-cell chronic lymphocytic leukemia (B-CLL).
Fluorescence in situ hybridization (FISH) has improved the detection of this
cytogenetic abnormality and has made detection possible in all phases of the cell
cycle. The presence of the trisomy 12 positive (+12) cell population has
generally been investigated in leukemic cells obtained from the peripheral blood
of CLL patients. To ascertain whether trisomy 12 is expressed homogeneously in
cells of different hemopoietic tissues, we applied FISH to lymph node, peripheral
blood and bone marrow samples obtained simultaneously from 23 untreated B-CLL
patients. DESIGN AND METHODS: Twenty-three newly diagnosed patients with B-CLL,
15 in stage B and 8 in stage C, were included in the present study. Peripheral
blood smears, bone marrow aspirate smears and lymph node touch imprints were
collected from each patient at diagnosis. Cytologic preparations were examined by
light microscopy in order to assess the lymphocyte morphology. Immunophenotyping
was performed by cytofluorimetric analysis of the peripheral blood, bone marrow
and lymph node mononuclear cell suspensions. The diagnosis was supported in all
cases by histologic findings in bone marrow biopsy and lymph node biopsy
specimens. Fluorescence in situ hybridization was performed on smears of blood
and aspirated bone-marrow and lymph node touch imprints obtained by fresh tissue
apposition. RESULTS: In 6 of the 23 cases (26%) trisomy 12 was clearly present in
all tissues examined. A comparative analysis of the three different hemopoietic
tissues was performed. A higher percentage of leukemic CD5+CD23+ cells was
detected in lymph nodes than in peripheral blood and bone marrow. A significantly
higher proportion of trisomic cells was observed in lymph nodes samples than in
peripheral blood or bone marrow smears of trisomy 12 positive CLL patients.
INTERPRETATION AND CONCLUSIONS: Several previous reports show that only a
proportion of malignant B-CLL cells carry trisomy 12 when analyzed by interphase
FISH. The higher proportion of +12 cells in lymph nodes than in peripheral blood
or bone marrow of CLL patients with trisomy 12 could reflect different cell
distributions in different tissues, or lymph node specific tropism, or
proliferative advantage in selected tissue. At present, the role of trisomy 12 in
the pathogenesis of lymphoproliferative disorders is unclear.
PMID- 10189385
TI - The degrees of plasma cell clonality and marrow infiltration adversely influence
the prognosis of AL amyloidosis patients.
AB - BACKGROUND AND OBJECTIVE: Primary amyloidosis is a lethal form of plasma cell
(PC) dyscrasia characterized by deposits of monoclonal immunoglobulin light
chains that cause organ dysfunction. In contrast to multiple myeloma, the amyloid
clone is typically indolent and of small size, and marrow PC clonality is not
always apparent. This is generally investigated by analyzing the light chain
isotype ratio in bone marrow PC. We investigated whether the degree of PC
infiltration (PC%) and clonality (PC isotype ratio) affected survival in 56
consecutive patients with primary amyloidosis. DESIGN AND METHODS: PC% was
determined by morphologic examination. Immunofluorescence microscopy was used to
determine the PC light chain isotype ratio. Statistical analysis was carried out
using Cox regression models. RESULTS: The degrees of PC clonality and
infiltration were inversely correlated with survival (PC isotype ratio, p =
0.001; PC%, p = 0.008). The two variables were weakly correlated (p = 0.02; r =
0.3). Bone marrow PC isotype ratio demonstrated a powerful independent prognostic
value at multivariate analysis when analyzed together with congestive heart
failure (the major known negative prognostic factor) and PC%. k/l ratio cut-off
values of 0.2 (l patients, p = 0.022) and 16 (k patients, p = 0.03) discriminated
two groups with a similar number of patients and significantly different
survivals. INTERPRETATION AND CONCLUSIONS: PC clonality and marrow infiltration
are important parameters that influence prognosis, presumably because they
reflect the amount of pathogenic light chain synthesis.
PMID- 10189386
TI - Early detection by ultrasound scan of severe post-chemotherapy gut complications
in patients with acute leukemia.
AB - BACKGROUND AND OBJECTIVE: Acute leukemia patients may develop life-threatening
gut complications after intensive chemotherapy. We evaluated the role of
abdominal and pelvic ultrasound (US) examination in early detection of these
complications. DESIGN AND METHODS: A cohort of twenty adult acute leukemia
patients undergoing intensive chemotherapy for remission induction entered the
study. All chemotherapy regimens included cytarabine by continuous i.v. infusion
for several days. RESULTS: Three patients had severe gut complications: 2 cases
of enterocolitis and 1 case of gall bladder overdistension in the absence of
calculi. In all cases the abnormality was documented by US examination: US scan
showed thickening of the intestinal wall (two cases), and gall bladder
overdistension with biliary sludge (one case). Immediate medical care included
bowel rest, a broad-spectrum antibiotic, antimycotic treatment, and granulocyte
colony-stimulating factor. All patients recovered from the complication.
INTERPRETATION AND CONCLUSIONS: We believe that the favorable outcome obtained in
our small series can be attributed to early diagnosis followed by appropriate
treatment. Early recognition by US and immediate medical management can lead to
complete recovery of severe intestinal complications in patients with acute
leukemia undergoing intensive chemotherapy.
PMID- 10189387
TI - Time sequential chemotherapy for primary refractory or relapsed adult acute
myeloid leukemia: results of the phase II Gemia protocol.
AB - BACKGROUND AND OBJECTIVE: High-dose cytarabine (HDAra-C), mitoxantrone and
etoposide are the mainstay of several active regimens against relapsed or
refractory acute myelogenous leukemia (AML). We designed a phase II study to
assess the efficacy and side effects of a time sequential application of
mitoxantrone plus intermediate-dose Ara-C followed by HDAra-C plus etoposide
(GEMIA) in adult patients with refractory or relapsed AML. DESIGN AND METHODS:
Patients with refractory or relapsed AML were eligible for GEMIA salvage therapy,
which comprised mitoxantrone 12 mg/m2/day on days 1-3, Ara-C 500 mg/m2/day as a
24-hour continuous infusion on days 1-3, followed by HDAra-C 2 g/m2/12-hourly on
days 6-8 and etoposide 100 mg/m2/12-hourly on days 6-8. Granulocyte colony
stimulating factor was started on day 14. In patients above the age of 55 the
dose of Ara-C in the first sequence (days 1-3) was reduced to 250 mg/m2. RESULTS:
Twenty patients were included, of whom 12 achieved complete remission after GEMIA
(60%, 95% CI 40-80%), one was refractory and five died early from infection. Two
additional patients achieved partial remission after GEMIA and complete remission
after consolidation chemotherapy, for a final CR rate of 70% (95% CI 48-88%).
Neutrophils recovered at a median of 27 days (range, 22-43) and platelets 46 days
(range, 25-59) after the start of treatment. The median duration of remission was
133 days (range, 36-417+) whereas overall survival time lasted for a median of
153 days (range, 13-554+). Treatment-associated toxicity was comprised
predominantly of infection, mucositis and diarrhea that reached World Health
Organization grades III-V in 40%, 40% and 30% of patients, respectively. Despite
the intention to rapidly proceed to a hematopoietic stem cell transplant in
patients in remission, only five patients reached the transplant. INTERPRETATION
AND CONCLUSIONS: The GEMIA time sequential chemotherapy regimen appears effective
in obtaining remissions in refractory and relapsed adult AML. The high toxicity
seen, however, suggests that its design is amenable to further improvements,
especially in more elderly patients. Since remissions are short-lived, more
innovative post-remission strategies are needed.
PMID- 10189388
TI - Randomized prospective study comparing cost-effectiveness of teicoplanin and
vancomycin as second-line empiric therapy for infection in neutropenic patients.
AB - BACKGROUND AND OBJECTIVE: The current health-care philosophy dictates that new
therapies should always be evaluated for their economic impact. Along with
acquisition cost, the cost of delivery, monitoring, adverse effects and treatment
failure must also be considered when determining the total cost of therapy. These
auxiliary costs can be significant and greatly alter the overall cost of a drug
treatment. We conducted a prospective randomized study to evaluate the efficacy,
safety and cost of vancomycin and teicoplanin therapy in patients with
neutropenia, after the failure of empirical treatment with a combination of
piperacillin/tazobactam and amikacin. DESIGN AND METHODS: Seventy-six febrile
episodes from 66 patients with hematologic malignancies under treatment,
neutropenia (neutrophils <500/mm3) and fever (38 degrees C twice or 38.5 degrees
C once) resistant to the combination piperacillin/tazobactam and amikacin were
included in the study. RESULTS: Primary success of second-line therapy was
obtained in 35 cases (46%) with no significant difference between vancomycin
(17/38) and teicoplanin arms (18/38). No difference in renal or hepatic toxicity
related to the antibiotic therapy was observed. The average cost per patient
according to glycopeptide used was $450+/-180 for the teicoplanin group and
$473+/-347 for the vancomycin group. Interestingly, in the teicoplanin arm, drug
acquisition accounted for 97% of the total cost, while in the vancomycin arm
administration and monitoring play an important role in overall costs.
INTERPRETATION AND CONCLUSIONS: In conclusion, our pharmacoeconomic analysis
demonstrates that teicoplanin and vancomycin can be administered in neutropenic
hematologic patients with similar efficacy and direct costs.
PMID- 10189389
TI - Feasibility and safety of a new technique of extracorporeal photochemotherapy:
experience of 240 procedures.
AB - BACKGROUND AND OBJECTIVE: Extracorporeal photochemotherapy (ECP) is a therapeutic
approach based on the biological effects of ultraviolet light (UV) - A and
psoralens on mononuclear cells collected by apheresis. Recently, ECP has been
under investigation as an alternative treatment for various immune and autoimmune
diseases. The aim of this study was to evaluate the safety and feasibility of a
new three-step ECP technique, in terms of reproducibility, acceptance,
tolerability, and short and long term side effects. DESIGN AND METHODS: Seventeen
patients affected by acute or chronic graft-versus-host disease (GvHD), pemphigus
vulgaris, or interferon-resistant chronic hepatitis C and one patient being
treated for prevention of heart transplant rejection underwent 240 ECP
procedures. MNC collection and processing parameters were recorded, biological
effects of UV-A/8 methoxy-psoralen (8-MOP) were evaluated, and short and long
term side effects were monitored. RESULTS: At a mean follow up of 7 months (range
2-19) 240 ECP had been completed, a mean of 7,136 mL (range 1,998-10,591) of
whole blood having beenprocessed per procedure. The mean of total nucleated cells
collected per procedure was 6.5x109 (range 0.65-23.8), with a mean MNC percentage
of 85% (41. 4-98%) in a mean final volume of 115.5 mL (37-160). No severe side
effects were documented and no infectious episodes occurred throughout the course
of the treatment. INTERPRETATION AND CONCLUSIONS: The new ECP technique was
highly reproducible as regards the collection and each processing step. Short and
long term side effects were mild. No increase in infectious episodes was
recorded. All patients willingly underwent ECP, demonstrating an excellent
tolerability for the procedure even after several courses.
PMID- 10189390
TI - Diagnostic approach to lymph node enlargement.
AB - BACKGROUND AND OBJECTIVE: How to reach the correct diagnosis of a lymph node
enlargement is still a problem which strongly challenges the knowledge and
experience of the clinician. Organized and specifically oriented literature on
the right sequential steps and the logical criteria that should guide this
diagnostic approach is still lacking. METHODS: The authors have tried to exploit
available knowledge and their personal experience by correlating a large body of
information regarding size, physical characteristics, anatomical location of
enlarged lymph nodes, and the possible epidemiological, environmental,
occupational and clinical categorization of this condition. RESULTS AND
CONCLUSIONS: It was intended that such material would have constituted the basis
of a hypothetic decision-making tree, but this was impossible because of the lack
of epidemiological investigation and registry data. Nevertheless, we present this
preparatory work here in order to stimulate the interest of concerned readers and
because of its possible direct usefulness in hematologic practice.
PMID- 10189391
TI - Iron overload in porphyria cutanea tarda.
AB - BACKGROUND AND OBJECTIVE: Porphyria cutanea tarda (PCT) is a disorder of
porphyrin metabolism associated with decreased activity of uroporphyrinogen
decarboxylase (URO-D) in the liver. The relevance of iron in the pathogenesis of
PCT is well established: iron overload is one of the factors that trigger the
clinical manifestations of the disease and iron depletion remains the cornerstone
of therapy for PCT. A role for genetic hemochromatosis in the pathogenesis of
iron overload in PCT has been hypothesized in the past but only after the recent
identification of the genetic defect causing hemochromatosis has the nature of
this association been partially elucidated. This review will outline current
concepts of the pathophysiology of iron overload in PCT as well as recent
contributions to the molecular epidemiology of hemochromatosis defects in PCT.
EVIDENCE AND INFORMATION SOURCES: The authors of the present review have a long
standing interest in the pathogenesis, etiology and epidemiology of iron overload
syndromes. Evidence from journal articles covered by the Science Citation
Index(R) and Medline(R) has been reviewed and collated with personal data and
experience. STATE OF THE ART AND PERPECTIVES: Mild to moderate iron overload
plays a key role in the pathogenesis of PCT. The recent identification of genetic
mutations of the hemochromatosis gene (HFE) in the majority of patients with PCT
confirms previous hypotheses on the association between PCT and hemochromatosis,
allows a step forward in the understanding of the pathophysiology of the
disturbance of iron metabolism in the liver of PCT patients, and provides an
easily detectable genetic marker which could have a useful clinical application.
Besides the epidemiological relevance of the association between PCT and
hemochromatosis, however, it remains to be fully understood how iron overload,
and in particular the cellular modifications of the iron status secondary to
hemochromatosis mutations, affect the activity of URO-D, and how the altered iron
metabolism interacts with the other two common triggers for PCT and etiological
agents for the associated liver disease: alcohol and hepatitis viruses. The
availability of a genetic marker for hemochromatosis will allow some of these
issues to be addressed by studying aspects of porphyrins and iron metabolism in
liver samples obtained from patients with PCT, liver disease of different
etiology and different HFE genotypes, and by in vitro studies on genotyped cells
and tissues.
PMID- 10189392
TI - Inflammation, sepsis, and coagulation.
AB - The molecular links between inflammation and coagulation are unquestioned.
Inflammation promotes coagulation by leading to intravascular tissue factor
expression, eliciting the expression of leukocyte adhesion molecules on the
intravascular cell surfaces, and down regulating the fibrinolytic and protein C
anticoagulant pathways. Thrombin, in turn, can promote inflammatory responses.
This creates a cycle that logically progresses to vascular injury as occurs in
septic shock. Most complex systems are regulated by product inhibition. This
inflammation-coagulation cycle seems to follow this same principle with the
protein C pathway serving as the regulatory mechanism. The molecular basis by
which the protein C pathway functions as an anticoagulant is relatively well
established compared to the mechanisms involved in regulating inflammation. As
one approach to identifying the mechanisms involved in regulating inflammation,
we set out to identify novel receptors that could modulate the specificity of APC
in a manner analogous to the mechanisms by which thrombomodulin modulates
thrombin specificity. This approach led to the identification of an endothelial
cell protein C receptor (EPCR). To understand the mechanism, we obtained a
crystal structure of APC (lacking the Gla domain). The crystal structure reveals
a deep groove in a location analogous to anion binding exosite 1 of thrombin, the
location of interaction for thrombomodulin, platelet thrombin receptor and
fibrinogen. Thrombomodulin blocks the activation of platelets and fibrinogen
without blocking reactivity with chromogenic substrates or inhibitors. Similarly,
in solution, EPCR blocks factor Va inactivation without modulating reactivity
with protease inhibitors. Thus, these endothelial cell receptors for the protein
C system share many properties in common including the ability to be modulated by
inflammatory cytokines. Current studies seek to identify the substrate for the
APC-EPCR complex as the next step in elucidating the mechanisms by which the
protein C pathway modulates the response to injury and inflammation.
PMID- 10189394
TI - Acute hemorrhagic leukoencephalitis in patients with acute myeloid leukemia in
hematologic complete remission.
AB - The authors describe the cases of three patients affected by acute myeloid
leukemia, in complete remission, who rapidly developed neurologic symptoms
leading to death. Neither clinical characteristics, nor radiological or
microbiological procedures, allowed an etiological diagnosis of the neurologic
syndrome. Post-mortem examination of the brain showed both macroscopic and
microscopic findings compatible with acute hemorrhagic leukoencephalitis. The
difficulty in distinguishing this entity from other CNS disease-related
complications (e.g. leukemia infiltration, drug toxicity, hemorrhages) should not
lead to an underestimation of the true incidence of this complication. We believe
that with more attention to the possibility of this complication there would
probably be both a greater possibility of collecting clinical informations about
the real impact of this dramatic disease and a stronger hope of finding the right
treatment for it.
PMID- 10189393
TI - Thrombotic thrombocytopenic purpura and autoimmunity: a tale of shadows and
suspects.
AB - BACKGROUND AND OBJECTIVE: The key pathogenic feature of TTP is the formation of
platelet aggregates within the microcirculation; however, the etiology of such
aggregates has been elusive for years. A large amount of evidence points to an
abnormal interaction between damaged vascular endothelium and platelets, although
the cause of the primary microvascular endothelial cell injury is seldom clear.
The autoimmune hypothesis often recurs, and this is based on a number of
observations: the claimed superiority of plasma-exchange over plasma infusion,
the anecdotal report of the presence of immunocomplexes and autoantibodies in TTP
patients, the efficacy of the administration of corticosteroids and other
immunosuppressant agents, and the concomitant occurrence of TTP in association
with autoimmune diseases, especially systemic lupus erythematosus (SLE). This
review will focus on the complex relationships between TTP and humoral
autoimmunity; in particular, similarities and differences between TTP, SLE and
antiphospholipid (aPL) antibodies syndrome, as well as the putative role of
several other antibodies directed towards endothelial cells and/or platelets,
including the recently discovered anti-CD36 antibodies and antivWF-cleaving
metalloprotease, will be discussed. DESIGN AND METHODS: The authors have been
involved in the study and treatment of TTP and autoimmune diseases for years;
furthermore, the PubMed data base of the National Library of Congress has been
extensively searched using the Internet. CONCLUSIONS: Although over the years
evidence has increased in favor of the autoimmune hypothesis for TTP
etiopathogenesis, TTP should not yet be considered an autoimmune disease.
Autoantibodies should be regarded as only one of the many different insults which
can trigger microvascular thrombosis even though the autoimmune theory of the
pathogenesis of TTP is gaining more and more strength. As far as concerns the
relationship between TTP, SLE and aPL antibodies-related disorders, these
diseases should be distinguished on the basis of both different clinical
presentations and accurate antibody screening, although this approach should
definitely not delay the prompt start of treatment.
PMID- 10189395
TI - A case of pseudothrombocytosis.
PMID- 10189396
TI - Clinical spectrum of porphyria cutanea tarda.
PMID- 10189398
TI - Preleukapheresis peripheral blood CD34+ cells predict progenitor cell collection
yield and the necessary number of procedures to undergo.
PMID- 10189397
TI - Detection of non-Hodgkin's lymphoma liver disease in cirrhotic patients.
PMID- 10189399
TI - Phenotypic changes in neutrophils after rhG-CSF administration in non-Hodgkin's
lymphoma patients undergoing PBSC transplantation or conventional chemotherapy.
PMID- 10189400
TI - Resolution of thrombocytopenia after treatment for Helicobacter pylori: a case
report.
PMID- 10189401
TI - HFE mutation analysis in patients with hepatitis C virus with positive screening
for iron overload.
PMID- 10189402
TI - Relevance of donor source to T-cell regeneration after bone marrow
transplantation for severe combined immunodeficiency.
PMID- 10189403
TI - Abnormalities of plasma von Willebrand factor multimeric structure induced by
extracorporeal circulation.
PMID- 10189404
TI - Acute myeloid leukemia M2b.
PMID- 10189405
TI - Soft tissue sarcoma of the extremities. A multimodality diagnostic and
therapeutic approach.
PMID- 10189406
TI - Effects of adjuvant chemotherapy on the natural history and likelihood of
therapeutic efficacy in advanced breast cancer patients: a critical literature
review.
PMID- 10189407
TI - Application of the area under the curve of carboplatin in predicting toxicity and
efficacy.
PMID- 10189408
TI - The systemic treatment of AIDS-related Kaposi's sarcoma.
PMID- 10189409
TI - Breakthrough pain in cancer patients: pathophysiology and treatment.
PMID- 10189410
TI - Mounting a defence against Alzheimer's disease.
PMID- 10189411
TI - Funding Medicare.
PMID- 10189412
TI - Funding Medicare.
PMID- 10189413
TI - Emergency stroke care.
PMID- 10189414
TI - Psychobiology of stroke: a neglected area.
PMID- 10189415
TI - Psychobiology of stroke: a neglected area.
PMID- 10189416
TI - Does the CMA's privacy code go too far? Or far enough?
PMID- 10189417
TI - Does the CMA's privacy code go too far? Or far enough?
PMID- 10189418
TI - The myth of freedom from conflict of interest.
PMID- 10189419
TI - Rehabilitation and stroke.
PMID- 10189420
TI - Signs of physical abuse or evidence of moxibustion, cupping or coining?
PMID- 10189421
TI - Contact tracing for pertussis.
PMID- 10189422
TI - Outcome of pulmonary tuberculosis treatment in the tertiary care setting--Toronto
1992/93. Tuberculosis Treatment Completion Study Group.
AB - BACKGROUND: Completion of treatment of active cases of tuberculosis (TB) is the
most important priority of TB control programs. This study was carried out to
assess treatment completion for active cases of pulmonary TB in Toronto. METHODS:
Consecutive cases of culture-proven pulmonary TB were obtained from the
microbiology laboratories of 5 university-affiliated tertiary care centres in
Toronto in 1992/93. A standard data-collection tool was used to abstract
information from inpatient and outpatient charts. For patients who were
transferred to other treatment centres or lost to follow-up, the local health
unit was contacted for information about treatment completion. If incomplete
information was obtained from these sources, data from the provincial Reportable
Disease Information System were also reviewed. The main outcome analysed was
treatment outcome, with cases classified as completed (record of treatment
completion noted), transferred (patient transferred to another centre but no
treatment results available), defaulted (record of defaulting in patient chart
but no record of treatment completion elsewhere, or patient still receiving
treatment more than 15 months after diagnosis) or dead (patient died before
treatment completion). RESULTS: Of the 145 patients 84 (58%) completed treatment,
25 (17%) died, 22 (15%) defaulted and 14 (10%) were transferred. The
corresponding values for the 22 patients with HIV coinfection were 6 (27%), 5
(23%), 8 (36%) and 3 (14%). Independent predictors of failure to complete
treatment were injection drug use (adjusted odds ratio [OR] 5.7, 95% confidence
interval [CI] 1.5 to 22.0), HIV infection (adjusted OR 4.6, 95% CI 1.4 to 14.7)
and adverse drug reaction (adjusted OR 2.9, 95% CI 1.1 to 7.9). Independent
predictors of death included age more than 50 years (adjusted OR 16.7, 95% CI 2.6
to 105.1), HIV infection (adjusted OR 16.1, 95% CI 3.9 to 66.4),
immunosuppressive therapy (adjusted OR 8.0, 95% CI 1.9 to 34.4) and infection
with a multidrug-resistant organism (adjusted OR 30.7, 95% CI 1.5 to 623.0).
INTERPRETATION: Treatment completion rates in tertiary care hospitals in Toronto
in 1992/93 were below the rate recommended by the World Health Organization.
Careful surveillance of treatment completion is necessary for the management of
TB in metropolitan centres in Canada.
PMID- 10189423
TI - Prevalence of Mycobacterium tuberculosis infection among injection drug users in
Toronto.
AB - BACKGROUND: Injection drug users are at increased risk of Mycobacterium
tuberculosis infection and active tuberculosis (TB). The primary objective of
this study was to determine the prevalence of M. tuberculosis infection among
injection drug users in Toronto, as indicated by a positive tuberculin skin test
result. An additional objective was to identify predictors of a positive skin
test result in this population. METHODS: A cross-sectional study was carried out
involving self-selected injection drug users in the city of Toronto. A total of
171 participants were recruited through a downtown Toronto needle-exchange
program from June 1 to Oct. 31, 1996. RESULTS: Of 167 subjects tested, 155
(92.8%) returned for interpretation of their skin test result within the
designated timeframe (48 to 72 hours). Using a 5-mm cut-off, the prevalence rate
of positive tuberculin skin test results was 31.0% (95% confidence interval 23.8%
to 38.9%). Birth outside of Canada and increasing age were both predictive of a
positive result. INTERPRETATION: There is a high burden of M. tuberculosis
infection in this population of injection drug users. The compliance observed
with returning for interpretation of skin test results indicates that successful
TB screening is possible among injection drug users.
PMID- 10189425
TI - Provision of intrapartum care by GP/FPs in Canada: an update.
PMID- 10189424
TI - Direct costs of coronary artery bypass grafting in patients aged 65 years or more
and those under age 65.
AB - BACKGROUND: Over the past 20 years, there have been marked increases in rates of
coronary artery bypass grafting (CABG) among older people in Canada. The
objectives of this study were to accurately estimate the direct medical costs of
CABG in older patients (age 65 years or more) and to compare CABG costs for this
age group with those for patients less than 65 years of age. METHODS: Direct
medical costs were estimated from a sample of 205 older and 202 younger patients
with triple-vessel or left main coronary artery disease who underwent isolated
CABG at The Toronto Hospital, a tertiary care university-affiliated hospital,
between Apr. 1, 1991, and Mar. 31, 1992. Costs are expressed in 1992 Canadian
dollars from a third-party payer perspective. RESULTS: The mean costs of CABG in
older and younger patients respectively were $16,500 and $15,600 for elective,
uncomplicated cases, $23,200 and $19,200 for nonelective, uncomplicated cases,
$29,200 and $20,300 for elective, complicated cases, and $33,600 and $23,700 for
nonelective, complicated cases. Age remained a significant determinant of costs
after adjustment for severity of heart disease and for comorbidity. Between 59%
and 91% of the cost difference between older and younger patients was accounted
for by higher intensive care unit and ward costs. INTERPRETATION: CABG was more
costly in older people, especially in complicated cases, even after an attempt to
adjust for severity of disease and comorbidity. Future studies should attempt to
identify modifiable factors that contribute to longer intensive care and ward
stays for older patients.
PMID- 10189426
TI - Alternative and complementary medicine in Canadian medical schools: a survey.
PMID- 10189427
TI - Body size, not sex, is responsible for differences in type of dialysis.
PMID- 10189428
TI - Optimizing tuberculosis control in the inner city.
PMID- 10189429
TI - Coronary artery bypass grafting in elderly patients: the price of success.
PMID- 10189430
TI - Improving outcomes for patients with schizophrenia: new hope for an old illness.
PMID- 10189431
TI - Sex or body size? Selection of dialysis type revisited.
PMID- 10189432
TI - Prostate cancer: 13. Whose prostate is it anyway? The view from the other side of
the examining table.
PMID- 10189433
TI - Tuberculosis: 1. Introduction.
PMID- 10189435
TI - An appreciation of A.E. Malloch, MB, MD (1844-1919): a forgotten surgical
pioneer.
AB - Dr. Archibald Edward Malloch was a surgeon whose life and work were greatly
influenced by Joseph Lister and his revolutionary system of antiseptic surgery.
This paper describes how a young Canadian medical man came to introduce Lister's
system to North America in 1869 and studies his career in the light of Lister's
surgical epoch.
PMID- 10189436
TI - Active and passive euthanasia: the cases of Drs. Claudio Alberto de la Rocha and
Nancy Morrison.
PMID- 10189434
TI - Improving outcome in schizophrenia: the case for early intervention.
PMID- 10189437
TI - Mumps in the era of vaccines.
PMID- 10189438
TI - OSLER marks first birthday with contest.
PMID- 10189439
TI - Huge court fight may be in offing as Ontario college considers penalty for
maverick MD.
AB - Physicians who practise alternative medicine are paying close attention to the
case of an Ontario physician who was found guilty of professional misconduct. The
College of Physicians and Surgeons of Ontario says it is simply doing its job.
PMID- 10189440
TI - Antivaccine advocates line up to support airman.
PMID- 10189441
TI - How many concussions are too many?
PMID- 10189442
TI - Military set to offer large signing bonuses, higher pay in face of unprecedented
MD staffing crisis.
PMID- 10189443
TI - Lack of time for communication creating "cycles of misinformation" about use of
antibiotics.
PMID- 10189444
TI - Protease inhibitors raising quality-of-life issues for HIV patients.
PMID- 10189445
TI - Calgary home to country's first comprehensive vascular birthmark clinic.
PMID- 10189446
TI - Visual expertise.
PMID- 10189447
TI - Differentiating benign from malignant enhancing lesions identified at MR imaging
of the breast: are time-signal intensity curves an accurate predictor?
PMID- 10189448
TI - Deep venous thrombosis: recent advances and optimal investigation with US.
AB - Compression US is the imaging procedure of choice for patients with clinically
suspected DVT of the lower and upper extremities. Clinical trials have validated
the safety of the approach of relying on two negative US studies obtained 1 week
apart to safely exclude the diagnosis of DVT. In selected low-risk patients, the
diagnosis of DVT may be excluded by a single negative US study. US has a role to
play in the management of patients with suspected pulmonary embolism who have
nondiagnostic pulmonary imaging studies.
PMID- 10189449
TI - Clinically important pulmonary emboli: does calf vein US alter outcomes?
AB - PURPOSE: To assess whether calf imaging is necessary to identify patients at risk
for developing clinically important pulmonary emboli (PE) or propagation of calf
deep venous thrombosis (DVT) when the initial thigh ultrasonographic (US) scan is
negative for DVT. MATERIALS AND METHODS: The authors retrospectively evaluated
the radiology reports from 283 patients (168 female and 115 male patients; mean
age, 55.7 years; age range, 1-93 years) in whom US was performed to rule out
lower extremity DVT. In all patients, the initial thigh examination was negative
for DVT. All patients were classified as to the reason for the examination, risk
factors for DVT (including recent surgery), whether they received anticoagulation
therapy, and findings on calf US scans. Adverse outcomes were considered a
clinically important PE or DVT in the thigh. RESULTS: Only 1.1% of patients (95%
CI = 0.2%, 3.1%) had adverse outcomes. Adverse outcomes occurred only in
postsurgical patients (P = .028) and were not related to the presence or absence
of calf DVT or method of treatment. CONCLUSION: US of the calf is unnecessary at
initial evaluation to identify patients at risk of clinically important PE or
propagation of DVT into the thigh.
PMID- 10189450
TI - Staging of rectal cancer after polypectomy: usefulness of endorectal US.
AB - PURPOSE: To determine the usefulness of endorectal ultrasonography (US) in
staging rectal cancer discovered at polypectomy. MATERIALS AND METHODS: Before
surgical resection, endorectal US was performed in 18 consecutive patients with
adenocarcinoma discovered in polypectomy specimens. A rotating 7-10-MHz endoprobe
with an inflatable balloon was used in all cases. The precise depth of
penetration (T stage) was determined with endorectal US and correlated with the
histopathologic findings. RESULTS: For detection of residual tumor after
polypectomy, endorectal US had a sensitivity of 100%, specificity of 44%,
positive predictive value of 64%, and negative predictive value of 100%. Although
the precise T stage was correctly predicted with endorectal US in only eight
patients (44%), endorectal US was able to demonstrate whether the tumor was
limited to the bowel wall in 16 patients (89%). CONCLUSION: Endorectal US is an
accurate technique for localizing tumors to or beyond the rectal wall in patients
who have undergone diagnostic polypectomy. Although inaccuracies in determining
the specific T stage may occur, endorectal US facilitates surgical planning in
the vast majority of patients and should therefore remain the local staging
technique of choice in this specific patient population.
PMID- 10189451
TI - The hyperattenuating crescent sign.
PMID- 10189452
TI - Catheter-directed thrombolysis for lower extremity deep venous thrombosis: report
of a national multicenter registry.
AB - PURPOSE: To evaluate catheter-directed thrombolysis for treatment of symptomatic
lower extremity deep venous thrombosis (DVT). MATERIALS AND METHODS: From a
registry of patients (n = 473) with symptomatic lower limb DVT, results of 312
urokinase infusions in 303 limbs of 287 patients (137 male and 150 female
patients; mean age, 47.5 years) were analyzed. DVT symptoms were acute (< or = 10
days) in 188 (66%) patients, chronic (> 10 days) in 45 (16%), and acute and
chronic in 54 (19%). A history of DVT existed in 90 (31%). Lysis grades were
calculated by using venographic results. RESULTS: Iliofemoral DVT (n = 221 [71%])
and femoral-popliteal DVT (n = 79 [25%]) were treated with urokinase infusions
(mean, 7.8 million i.u.) for a mean of 53.4 hours. After thrombolysis, 99 iliac
and five femoral vein lesions were treated with stents. Grade III (complete)
lysis was achieved in 96 (31%) infusions; grade II (50%-99% lysis), in 162 (52%);
and grade I (< 50% lysis), in 54 (17%). For acute thrombosis, grade III lysis
occurred in 34% of cases of acute and in 19% of cases of chronic DVT (P < .01).
Major bleeding complications occurred in 54 (11%) patients, most often at the
puncture site. Six patients (1%) developed pulmonary emboli. Two deaths (< 1%)
were attributed to pulmonary embolism and intracranial hemorrhage. At 1 year, the
primary patency rate was 60%. Lysis grade was predictive of 1-year patency rate
(grade III, 79%; grade II, 58%; grade I, 32%; P < .001). CONCLUSION: Catheter
directed thrombolysis is safe and effective. These data can guide patient
selection for this therapeutic technique.
PMID- 10189453
TI - Hepatic blood supply: comparison of optimized dual phase contrast-enhanced three
dimensional MR angiography and digital subtraction angiography.
AB - PURPOSE: To optimize and determine the value of dual-phase contrast material
enhanced three-dimensional (3D) magnetic resonance (MR) angiography for
preoperative evaluation of the blood supply to the liver. MATERIALS AND METHODS:
Dual phase 3D MR angiography of the hepatic arteries and portal vein was
performed in 140 patients. In 80 patients, the value of fat saturation, digital
image subtraction, an anticholinergic agent, and a high-caloric meal were
evaluated. In the next 60 patients, MR angiographic and digital subtraction
angiographic (DSA) image quality and diagnostic value were compared. RESULTS: Fat
saturated images were of significantly better quality (P < .01) than non-fat
saturated images. Digital image subtraction was useful in only 23 of 40 patients.
The injection of an anticholinergic agent was superfluous, whereas administration
of a high-caloric meal helped in demonstration of the superior mesenteric artery
and portal vein. Classification on MR angiograms of the arterial blood supply was
correct in 57 of 60 patients. All arterial and portal venous lesions were seen on
MR angiograms, and MR angiograms had a significantly higher subjective image
quality ranking than did DSA images in the evaluation of the portal vein (P <
.05). CONCLUSION: Fat saturation and use of a high-caloric meal improve the
results of MR angiography of hepatic vessels. MR angiography was comparable to
DSA for evaluation of the arterial system and was superior for demonstration of
the portal vein; therefore, MR angiography could replace intraarterial DSA.
PMID- 10189454
TI - Stepping-table gadolinium-enhanced digital subtraction MR angiography of the
aorta and lower extremity arteries: preliminary experience.
AB - PURPOSE: To compare stepping-table digital subtraction gadolinium-enhanced
magnetic resonance (MR) angiography of the distal aorta and lower extremity
arteries with conventional catheter digital subtraction x-ray angiography in
patients with arterio-occlusive disease. MATERIALS AND METHODS: Twenty patients
underwent both conventional catheter angiography and fast three-dimensional
gadolinium-enhanced MR angiography of the aorta and outflow vessels at 1.5 T; the
images were acquired in three consecutive imaging locations during a single
infusion of a gadolinium chelate. RESULTS: Compared with catheter angiography,
according to the findings of two blinded independent reviewers, MR angiography
had sensitivities of 81% and 89% and specificities of 91% and 95%, respectively,
for demonstration of insignificant (< or = 50%) stenosis versus significant (51%
100%) stenosis. For demonstration of occlusion, the sensitivity and specificity
were 94% and 97%, respectively, by consensus. There was good interobserver
correlation between the two readers overall (kappa = 0.65 for reporting the
degree of narrowing in all lesions; 0.86, for reporting of insignificant versus
significant stenoses; and 0.928, for reporting of occluded versus patient
segments). CONCLUSION: Stepping-table digital subtraction contrast material
enhanced MR angiography has high accuracy compared with catheter angiography in
patients with arterio-occlusive disease of the aorta and outflow vessels. These
preliminary study results suggest that this technique may ultimately provide a
safe, noninvasive, and cost-effective alternative to catheter angiography.
PMID- 10189455
TI - Single-dose breath-hold gadolinium-enhanced three-dimensional MR angiography of
the renal arteries.
AB - PURPOSE: To evaluate the quality of single-dose breath-hold three-dimensional
(3D) magnetic resonance (MR) angiography of the renal arteries optimized with a 1
mL test bolus timing examination. MATERIALS AND METHODS: Three-dimensional
spoiled gradient-echo imaging (3.8-4.2/1.3-1.7 [repetition time msec/echo time
msec], 25 degrees-40 degrees flip angle) was performed in 60 patients after
administration of gadopentetate dimeglumine (average dose, 0.11 mmol/kg).
Synchronization of contrast material administration with data acquisition was
achieved with a 1-mL test dose of contrast material to estimate patient
circulation parameters. Image quality was assessed by using contrast-to-noise
(CNR), relative vascular enhancement, and venous-to-arterial enhancement ratios
and subjective scoring of arterial and venous enhancement. The effect of the
contrast material injection rate and the influence of breath holding during the
timing examination also were examined. RESULTS: Overall, of 60 studies, 58 were
diagnostic and 56 demonstrated excellent arterial enhancement. Venous enhancement
was seen in eight studies. The average aortic relative vascular enhancement (+/-
SD) was 14.6 +/- 5.9, with an aorta-to-inferior vena cava (IVC) CNR of 69.7 +/-
43.9. The IVC-to-aorta venous-to-arterial enhancement ratio averaged 0.08 +/-
0.16. There was no significant difference in image quality based on injection
rates or the performance of breath holding during the timing examination (P >
.1). CONCLUSION: Breath-hold gadolinium-enhanced renal MR angiography free of
venous enhancement can be performed consistently and reliably with 20 mL of
contrast material when studies are synchronized to patient circulation time by
using a timing examination.
PMID- 10189456
TI - Diagnosis please. Case 9: mycotic pseudoaneurysm of the abdominal aorta in
association with mycobacterial psoas abscess--a complication of BCG therapy.
PMID- 10189457
TI - Assessment of a bolus-tracking technique in helical renal CT to optimize
nephrographic phase imaging.
AB - PURPOSE: To evaluate a bolus-tracking technique in helical computed tomography
(CT) for identifying the onset of the nephrographic phase and to determine the
effect of varying the volume and injection rate of contrast material on
nephrographic phase onset. MATERIALS AND METHODS: Seventy-five patients underwent
bolus tracking of contrast material followed by helical renal CT. In 50 patients,
150 mL of 60% iodinated contrast material (iohexol or iothalamate meglumine) was
injected at either 2 mL/sec (25 patients [group 1]) or 3 mL/sec (25 patients
[group 2]). In 25 patients who had previously undergone nephrectomy, 100 mL of
60% iodinated contrast material was injected at 3 mL/sec (group 3). Nephrographic
phase onset was determined by visually assessing the transition to a homogeneous
nephrogram during a monitoring scan series starting 40 seconds after injection.
RESULTS: Nephrographic phase onset ranged from 60 to 136 seconds (mean, 89
seconds +/- 17 [+/- SD]). Statistically significant differences in mean onset
times were observed among groups 1 (103 seconds +/- 12), 2 (91 seconds +/- 16),
and 3 (75 seconds +/- 9) (P < .001). Multiple regression analysis showed patient
age, contrast material volume, and injection rate to be independent predictors of
nephrographic phase onset. Contrast material volume, patient age, and patient
weight were independent predictors of the degree of renal enhancement.
CONCLUSION: Nephrographic phase onset is highly dependent on methods of contrast
material administration and patient characteristics.
PMID- 10189458
TI - Complex posttransplantation abnormalities of renal allografts: evaluation with MR
imaging.
AB - PURPOSE: To assess the efficacy of magnetic resonance (MR) imaging in the
evaluation of complex abnormalities of renal allografts. MATERIALS AND METHODS:
Clinical and radiologic findings were retrospectively reviewed in 24 patients who
underwent MR imaging of a renal allograft because ultrasonographic (US) findings
were inconclusive or discordant with clinical findings. The final diagnoses were
established with histopathologic analysis (n = 16) or clinical and imaging follow
up (n = 8). RESULTS: MR imaging diagnoses were correct in 16 patients (67%),
whereas US diagnoses were correct in six patients (25%) (P < .05). Five cases of
allograft involvement by posttransplantation lymphoproliferative disorder (PTLD)
were found at histopathologic analysis; at MR imaging, PTLD appeared as
hypointense masses on T1-and T2-weighted images with minimal enhancement. In four
of the five cases of PTLD, the masses occurred at the renal hilum and encased
hilar vessels. Normal morphology was correctly diagnosed with MR imaging in five
patients in whom a mass was suspected at US. CONCLUSION: MR imaging results are
often diagnostic in cases of complex abnormalities of renal allografts. Renal
allograft involvement by PTLD appears to have a relatively characteristic MR
imaging appearance. Normal MR imaging findings in cases of suspected masses at US
may obviate biopsy.
PMID- 10189459
TI - Dynamic breast MR imaging: are signal intensity time course data useful for
differential diagnosis of enhancing lesions?
AB - PURPOSE: To assess the relevance of the signal intensity time course for the
differential diagnosis of enhancing lesions in dynamic magnetic resonance (MR)
imaging of the breast. MATERIALS AND METHODS: Two hundred sixty-six breast
lesions were examined with a two-dimensional dynamic MR imaging series and
subtraction postprocessing. Time-signal intensity curves of the lesions were
obtained and classified according to their shapes as type I, which was steady
enhancement; type II, plateau of signal intensity; or type III, washout of signal
intensity. Enhancement rates and curve types of benign and malignant lesions were
compared. RESULTS: There were 101 malignant and 165 benign lesions. The
distribution of curve types for breast cancers was type I, 8.9%; type II, 33.6%;
and type III, 57.4%. The distribution of curve types for benign lesions was type
I, 83.0%; type II, 11.5%; and type III, 5.5%. The distributions proved
significantly different (chi 2 = 139.6; P < .001). The diagnostic indices for
signal intensity time course were sensitivity, 91%; specificity, 83%; and
diagnostic accuracy, 86%. The diagnostic indices for the enhancement rate were
sensitivity, 91%; specificity, 37%; and diagnostic accuracy, 58%. CONCLUSION: The
shape of the time-signal intensity curve is an important criterion in
differentiating benign and malignant enhancing lesions in dynamic breast MR
imaging. A type III time course is a strong indicator of malignancy and is
independent of other criteria.
PMID- 10189460
TI - Developing asymmetric breast tissue.
AB - PURPOSE: To show that benign asymmetric breast tissue detected mammographically
may increase over time. MATERIALS AND METHODS: Serial mammograms obtained in 21
women with negative physical examination results and mammographically detected
developing asymmetric breast tissue were reviewed, and findings were correlated
with results of biopsy (n = 16), ultrasonography (US) (n = 8), and contrast
material-enhanced magnetic resonance (MR) imaging (n = 3). Five patients who did
not undergo biopsy were followed up for 13-84 months. Thirteen of 16 biopsy
specimens were reviewed. RESULTS: At the time of mammographic change, 12 patients
without baseline asymmetric tissue had a mean age of 41.7 years and a mean size
of asymmetric tissue of 2.4 cm. The mean age of nine patients with baseline
asymmetric tissue was 46.9 years. In eight patients, the mean size increase was
2.5 cm. One patient showed increased tissue density but stable size. All US and
MR images were negative. Pseudoangiomatous stromal hyperplasia was present in all
13 biopsy specimens reviewed and extensive in 12. No malignancies have been
reported in five of the followed-up patients, and two have had continued
enlargement of asymmetric tissue. CONCLUSION: Pseudoangiomatous stromal
hyperplasia is a common histopathologic finding in developing asymmetric breast
tissue. Follow-up, rather than biopsy, is a management option if benign imaging
and clinical criteria are met.
PMID- 10189461
TI - Total-body echo-planar MR imaging in the staging of breast cancer: comparison
with conventional methods--early experience.
AB - PURPOSE: To test breast cancer staging with total-body echo-planar magnetic
resonance (MR) imaging. MATERIALS AND METHODS: Nineteen patients with newly
diagnosed breast cancer were imaged by using a 1.5-T echo-planar MR system. By
using a table sweep method, 180 contiguous axial images were obtained from the
cranial vertex through the feet with T2-weighted spin-echo and inversion-recovery
sequences. Results were compared with those of conventional imaging. Therapeutic
decisions based on echo-planar MR imaging and conventional imaging results were
compared. Diagnostic truth was determined by means of tissue diagnosis, further
imaging findings, and follow-up findings (median, 18 months). RESULTS: Staging
with total-body echo-planar MR imaging was correct in 18 patients (95%)--eight
with metastases and 10 without--while staging with conventional imaging was
correct in 15 patients (79%). In one patient, both echo-planar MR imaging and
conventional imaging findings incorrectly indicated probable metastases. In one
patient thought to have bone metastases at conventional imaging, echo-planar MR
imaging findings were normal, which was correct. Two patients with stage IV
disease were not suspected to have disease at conventional imaging: One had liver
involvement and the other had skeletal metastases. The therapeutic decisions in
these two patients were altered by the echo-planar MR imaging results.
CONCLUSION: Total-body echo-planar MR imaging was at least as accurate as
conventional imaging for staging newly diagnosed breast cancer and was faster,
simpler, and completely noninvasive.
PMID- 10189462
TI - Hypertrophic cardiomyopathy: MR measurement of coronary blood flow and
vasodilator flow reserve in patients and healthy subjects.
AB - PURPOSE: To evaluate coronary blood flow per gram of myocardial mass and
vasodilator flow reserve in patients with hypertrophic cardiomyopathy (HCM) and
in healthy subjects by using breath-hold velocity-encoded cine (VEC) magnetic
resonance (MR) imaging. MATERIALS AND METHODS: Twenty-nine patients with HCM and
nine healthy volunteers were examined. Fast VEC MR images were obtained in an
oblique imaging plane perpendicular to the coronary sinus before and after
intravenous injection of dipyridamole (0.56 mg/kg). The products of mean velocity
and cross-sectional area of the vessel were integrated to measure blood flow.
Breath-hold cine MR images encompassing the entire left ventricle were acquired
to quantify the left ventricular mass. RESULTS: In the basal state, the coronary
blood flow per gram of myocardial mass was 0.74 mL/min/g +/- 0.23 in healthy
subjects and 0.62 mL/min/g +/- 0.27 in patients with HCM. After administration of
dipyridamole, coronary blood flow in patients with HCM increased to a level
significantly less than that in healthy subjects (1.03 mL/min/g +/- 0.40 vs 2.14
mL/min/g +/- 0.51; P < .01), resulting in a severely depressed flow reserve ratio
in patients with HCM compared with that in healthy subjects (1.72 +/- 0.49 vs
3.01 +/- 0.75; P < .01). CONCLUSION: Breath-hold VEC MR imaging is a noninvasive
technique for evaluating coronary flow per gram of myocardial mass and coronary
flow reserve.
PMID- 10189463
TI - Suspected non-small cell lung cancer: incidence of occult brain and skeletal
metastases and effectiveness of imaging for detection--pilot study.
AB - PURPOSE: To estimate the incidence of occult metastases to the brain and skeleton
in patients suspected of having non-small cell lung cancer (NSCLC) (stage higher
than T1Nomo) with surgically resectable disease, to assess the accuracy of
screening magnetic resonance (MR) imaging and radionuclide bone scanning for help
in identifying occult metastases, and to determine the effectiveness of a high
dose of MR contrast material. MATERIALS AND METHODS: Twenty-nine patients
suspected of having NSCLC localized to the lung or to the lung and regional nodes
underwent preoperative MR imaging with contrast material enhancement and
radionuclide bone scanning for detection of brain or skeletal metastases.
Patients were followed up for 12 months to determine the incidence of clinical
metastatic disease. RESULTS: Eight (28%) patients had occult metastatic disease
to the brain or skeleton. Brain metastases were identified on MR images in five
of six patients. Bone metastases were identified on MR images in four of five
patients and on bone scans in three of five patients. MR imaging was no more
accurate than bone scanning for skeletal evaluation. A high dose of MR contrast
material allowed detection of more metastases and of small lesions. CONCLUSION:
Contrast-enhanced MR imaging of the brain is indicated for the exclusion of brain
metastases in patients with clinically operable known or possible NSCLC and a
large (> 3-cm) lung mass. Skeletal imaging may be indicated if an isolated brain
metastasis is detected.
PMID- 10189464
TI - Parenchymal and pleural findings in patients with and patients without acute
pulmonary embolism detected at spiral CT.
AB - PURPOSE: To compare the frequencies of parenchymal abnormalities and pleural
effusions in patients with and patients without acute pulmonary embolism (PE)
detected at spiral computed tomography (CT). MATERIALS AND METHODS: Contrast
material-enhanced spiral CT scans obtained in 92 patients clinically suspected of
having acute PE were retrospectively reviewed. The presence or absence of
parenchymal abnormalities and pleural effusions was noted. The presence of
filling defects consistent with central or peripheral PE was recorded. RESULTS:
Twenty-eight patients had CT evidence of PE. Central emboli were evident in 27
(96%) of these patients; 23 (82%) had concomitant central and peripheral emboli,
and four (14%) had only central emboli. One patient had an isolated subsegmental
clot. Parenchymal abnormalities were seen in 24 (86%) patients with PE and 56
(88%) patients without PE. Atelectasis, the most common finding, was present in
20 (71%) patients with PE and 41 (64%) patients without PE. The only parenchymal
abnormality significantly associated with PE was peripheral wedge-shaped opacity,
which was seen in seven (25%) patients with PE and three (5%) patients without PE
(odds ratio, 6.78; 95% CI = 1.60, 28.62). Pleural effusions were seen in 16 (57%)
patients with PE and 36 (56%) patients without PE. In 25 (39%) patients without
PE, there were additional CT findings that might suggest an alternative
explanation for the acute clinical presentation. CONCLUSION: Parenchymal and
pleural findings at CT are of limited value for differentiating patients with PE
from those without PE.
PMID- 10189465
TI - Crazy-paving appearance at thin-section CT: spectrum of disease and pathologic
findings.
AB - PURPOSE: To determine the spectrum of disease associated with a fine reticular
pattern superimposed on areas of ground-glass opacity (i.e., "crazy-paving"
appearance) at thin-section computed tomography (CT) and to determine the
underlying pathologic features. MATERIALS AND METHODS: In the in vivo study, the
cases of 46 patients (21 male, 25 female; age range, 13-82 years) were
retrospectively reviewed, with special attention paid to the size and extent of
the reticular network. In the in vitro study, the thin-section CT findings in 20
inflated and fixed lungs were precisely correlated with the gross appearance,
contact radiograph findings, stereomicroscopic views, and histologic findings.
RESULTS: In the in vivo study, 15 different diseases were identified, including
alveolar proteinosis, adult respiratory distress syndrome, acute interstitial
pneumonia, diffuse alveolar damage superimposed on usual interstitial pneumonia,
and drug-induced pneumonitis. In the in vitro study, the fine networks at
pathologic analysis were due to an alveolar filling process (n = 10), an
interstitial fibrotic process (n = 7), or a combination of interstitial and
intraalveolar processes (n = 3). Twelve (60%) cases did not have thickening of
the interlobular septa within the areas of the crazy-paving appearance.
CONCLUSION: The crazy-paving appearance is a nonspecific finding seen in a
variety of interstitial and airspace lung diseases.
PMID- 10189466
TI - Hydrostatic pulmonary edema: evaluation with thin-section CT in dogs.
AB - PURPOSE: To identify the hemodynamic determinants of ground-glass opacification
on thin-section computed tomographic (CT) scans of hydrostatic pulmonary edema
and to compare attenuation and subjective assessments of ground-glass
opacification with extravascular lung water. MATERIALS AND METHODS: Left atrial
pressure, pulmonary arterial pressure, effective pulmonary capillary pressure,
and extravascular lung water were measured in six dogs before and during
progressive increase of effective pulmonary capillary pressure. A thin-section CT
scan was obtained at each step. Lung attenuation and subjective assessments of
ground-glass opacification were compared with hemodynamic variables and
extravascular lung water. RESULTS: Ground-glass opacification was identified when
effective pulmonary capillary pressure equaled critical pulmonary capillary
pressure. Extravascular lung water increased, and the distribution curve of lung
attenuation coefficients shifted to higher attenuation from the second
measurement at an effective pulmonary capillary pressure greater than the
critical pulmonary capillary pressure. Attenuation was highly correlated (r =
0.98, P < .001) with extravascular lung water; ground-glass opacification was
detected before a significant (P = .615, analysis of variance) increase in
extravascular lung water. CONCLUSION: Thin-section CT depicts ground-glass
opacification when effective pulmonary capillary pressure equals critical
pulmonary capillary pressure and before a detectable increase in extravascular
lung water. Attenuation reflects extravascular lung water.
PMID- 10189467
TI - Polyethylene terephthalate and polyurethane coatings for endovascular stents:
preliminary results in canine experimental arteriovenous fistulas.
AB - PURPOSE: To evaluate polyethylene terephthalate and polyurethane as coatings of
vascular endoprostheses in the treatment of experimental arteriovenous fistulas
(AVFs). MATERIALS AND METHODS: Nineteen bilateral carotid artery-to-external
jugular vein AVFs were created in 10 adult dogs. Fourteen polyethylene
terephthalate-coated and five polyurethane-coated self-expandable nitinol stents
were placed with a transfemoral approach. Angiography was performed immediately
after placement, after 1 and 3 weeks, and at months 3, 6, 9, and 12. All grafts
were examined histopathologically. RESULTS: The AVF was successfully occluded
with all but one of the polyethylene terephthalate-coated stents. Graft patency
was seen with 12 polyethylene terephthalate-coated stents, while acute vessel
occlusion was evident with two polyethylene terephthalate-coated stents following
percutaneous transluminal angioplasty immediately after implantation. In the
group with polyurethane-coated stents, three graft dislocations and two delayed
vessel occlusions were observed. In both groups, histologic examination disclosed
a mild foreign body reaction with a few macro-phages. No inflammatory reactions
were seen. An unorganized fibrin layer was found adjacent to the polyurethane
coating. CONCLUSION: Polyethylene terephthalate-coated nitinol stents showed good
biocompatibility and a high rate of occlusion of experimental AVFs. The
mechanical properties of the polyethylene terephthalate coating were similar to
those of the nitinol stents, which facilitated handling. Polyurethane-coated
stents showed frequent dislocation.
PMID- 10189468
TI - Changes in rat liver microcirculation after experimental hepatic arterial
embolization: comparison of different embolic agents.
AB - PURPOSE: To evaluate the effects of hepatic arterial embolization on hepatic
microcirculation in the rat liver by using different particulate agents.
MATERIALS AND METHODS: Polylactic acid microspheres, polyvinyl alcohol particles,
and absorbable gelatin powder were injected into the hepatic artery of 50 rats.
Saline was used as the control agent. Flow characteristics of hepatic
microcirculation were qualitatively assessed on days 0 and 7 after embolization
by using in vivo microscopy. Histologic specimens of the rat liver were analyzed.
RESULTS: The polylactic acid (1-5 microns) injected into the hepatic artery was
seen circulating through the sinusoids into the central venules. The slowing of
flow observed with the injection of larger (50-200-micron) particles reflected
the arterial occlusion occurring more proximally. After 7 days, all embolic
agents caused vascular occlusion that led to necrosis and fibrosis. Networks of
irregular, high-speed vessels that resembled arterioles and bypassed the normal
sinusoids were observed. CONCLUSION: The necrotic areas observed after
experimental distal occlusion of the hepatic arteries in the rats were bypassed
by vessels similar to the capillarized sinusoids observed in the cirrhotic liver
in humans. These vessels acted as sinusoidal shunts in the embolized territories.
PMID- 10189469
TI - Primary non-Hodgkin lymphoma of the small bowel.
AB - PURPOSE: To clarify the natural history of primary lymphoma of the small bowel
and identify preferred treatments for it. MATERIALS AND METHODS: A retrospective
analysis of 61 patients with primary lymphoma of the small bowel was performed.
The Ann Arbor stages were I in 20 patients, II in 28, and IV in 13. After
resection or biopsy, 15 patients were treated with radiation therapy, 26 with
chemotherapy, and 16 with combined-modality therapy. Four patients underwent no
adjuvant treatment after resection. RESULTS: The actuarial 10-year overall
survival and relapse-free survival for the patients with intermediate- and high
grade lymphoma were 47% and 53%, respectively. For the patients with low-grade
lymphoma, these rates were 81% and 62%. For patients who underwent radiation
therapy, combined-modality therapy, or chemotherapy, the recurrence rates inside
the abdomen or pelvis were one of 12, two of 15, and five of 20, respectively,
and those outside the abdomen or pelvis were four of 12, one of 15, and zero of
20, respectively. Four of the five abdominopelvic recurrences of disease in the
chemotherapy group were among the nine patients who had Ann Arbor stage II
disease. CONCLUSION: Chemotherapy lowered the recurrence rate outside the abdomen
or pelvis. Patients with stage II disease may benefit most from radiation
therapy.
PMID- 10189470
TI - Evaluation of a 10-minute comprehensive MR imaging examination of the upper
abdomen.
AB - PURPOSE: To determine whether a 10-minute magnetic resonance (MR) imaging
examination of the upper abdomen provides sufficiently comprehensive information
to replace a longer MR protocol. MATERIALS AND METHODS: Images obtained with
selected breathing-independent and breath hold MR sequences, with 2 minutes of
total acquisition time and an estimated 10 minutes of total study time, in
consecutive MR examinations of the upper abdomen in 72 patients (age range, 23-87
years) were retrospectively reviewed in a blinded fashion by two separate
interpreters. Determination was made of major and minor findings, and the two
separate retrospective interpretations and the prospective clinical
interpretation were correlated by using kappa statistics. Surgical and clinical
findings were also correlated with imaging findings. RESULTS: In 61 patients, all
major and minor findings were identical in the original clinical interpretation
and the two retrospective readings. In 66 patients, the major findings were
identical in these three readings. Close agreement was present between the two
separate retrospective readings and the prospective clinical interpretation
(kappa = 0.49-1.00). CONCLUSION: The findings suggest that the diagnostic
information provided by a shortened MR imaging protocol that includes breath-hold
and breathing-independent sequences is in close agreement with lengthier MR
protocols. The advantages of a shortened protocol include increased patient
throughput and decreased study cost.
PMID- 10189471
TI - Modified small-bowel follow-through: use of methylcellulose to improve bowel
transradiance and prepare barium suspension.
AB - PURPOSE: To evaluate the efficacy of barium suspension prepared in
methylcellulose (MC) in modified small-bowel follow-through (SBFT). MATERIALS AND
METHODS: The authors evaluated 155 patients who underwent modified SBFT with oral
administration of MC after ingesting barium suspension. Of these patients, 52
received 40% suspension in MC, 46 received 40% suspension in water, and 57
received 70% suspension in water. Patients were divided into normal (n = 74) and
abnormal (n = 81) groups according to the final results. The image quality,
transit time to the cecum, and time to and frequency of flocculation were
compared for both groups. RESULTS: In the normal group, the quality of the images
in patients receiving 40% suspension in MC or 70% suspension in water was
superior to that of images in patients receiving 40% suspension in water. In the
abnormal group, the best image quality was achieved for the patients who received
40% suspension in MC. In the normal group, the difference in transit time between
the three preparations was not substantial. In the abnormal group, however, the
40% suspension in MC showed the fastest transit time. Use of the 40% suspension
in MC helped lower the frequency of flocculation in the normal group. CONCLUSION:
Use of 40% barium suspension in MC is effective for improving the image quality
in modified SBFT.
PMID- 10189472
TI - CT features of systemic lupus erythematosus in patients with acute abdominal
pain: emphasis on ischemic bowel disease.
AB - PURPOSE: To evaluate the computed tomographic (CT) features of systemic lupus
erythematosus (SLE) in patients with acute abdominal pain. Special emphasis was
placed on the analysis of ischemic bowel disease. MATERIALS AND METHODS: The
authors retrospectively reviewed the images from 39 abdominal CT examinations
performed in 33 patients with SLE and acute abdominal pain. Images were evaluated
for bowel wall changes, mesenteric changes, fluid collection, retroperitoneal
lymphadenopathy, peritoneal enhancement, and hepatomegaly as well as for changes
in other abdominal organs. Ischemic bowel disease was diagnosed if at least three
of the following signs were seen: bowel wall thickening, target sign, dilatation
of intestinal segments, engorgement of mesenteric vessels, and increased
attenuation of mesenteric fat. RESULTS: Thirty-one (79%) of the 39 examinations
had CT findings diagnostic of ischemic bowel disease, including symmetric bowel
wall thickening (n = 29), target sign (n = 26), and mesenteric vascular
engorgement and haziness (n = 31). In 24 cases, bowel wall thickening was
multifocal, with variable length, and did not appear to be confined to a single
vascular territory. CONCLUSION: The most common CT finding in patients with SLE
and acute abdominal pain is ischemic bowel disease. CT is useful for detecting
the primary cause of gastrointestinal symptoms, planning treatment, and
monitoring for infarction or perforation.
PMID- 10189473
TI - Colon cancer at barium enema examination and colonoscopy: a study from the county
of Hordaland, Norway.
AB - PURPOSE: To evaluate the efficacy of barium enema examination as routinely
performed in the detection of colon cancer in the inhabitants of a well-defined
and circumscribed geographic region. MATERIALS AND METHODS: The study comprised
571 patients with histopathologically verified colon cancer during 1990-1993 from
the county of Hordaland. The barium enema examination results were reviewed
retrospectively. RESULTS: The correct diagnosis was reached in 351 cases
(sensitivity, 90.9%) in 386 tumor locations on the basis of the results of 381
barium enema examinations. Cancer or an important precancerous lesion was
overlooked in 26 cases (6.7%), and the examination was not feasible in nine cases
(2.3%). The correct diagnosis was reached in 172 cases (sensitivity, 80.0%) in
patients with 215 tumor locations on the basis of the results of 213
colonoscopies. Cancer or an important precancerous lesion was overlooked in 13
cases (6.0%). The examination was technically not successful (i.e., the affected
area was not reached with the scope) in 30 cases (13.9%). CONCLUSION: Barium
enema examination is valuable in the diagnosis of colon cancer and compares
favorably with colonoscopy. The main reason for missed radiologic diagnosis is
failure to observe important lesions visible on the radiographs.
PMID- 10189474
TI - Rectal carcinoma: thin-section MR imaging for staging in 28 patients.
AB - PURPOSE: To evaluate the accuracy of thin-section magnetic resonance (MR) imaging
(in-plane resolution, 0.6 x 0.6 mm) in the preoperative assessment of the depth
of extramural tumor infiltration, which is a major prognostic indicator in rectal
cancer. MATERIALS AND METHODS: In a prospective study of 28 consecutive patients,
preoperative MR imaging was performed. The tumor stage according to the TNM
classification system and the measured depth of extramural tumor invasion in
matched MR images and histopathologic slices were compared. RESULTS: Preoperative
MR imaging correctly indicated the histopathologic tumor stage in all 25 patients
in whom comparisons were possible. The difference between the depth of extramural
tumor measured on preoperative MR images and corresponding measurements on
histopathologic slices of the resection specimen ranged from -5.0 mm to +5.5 mm
(mean difference, +0.13 mm; 95% CI: -2.72, +2.98 mm), indicating good agreement.
The mesorectal fascia, and the relation of the tumor to it, could be visualized
in every case. In all five patients with involvement of the circumferential
excision margins of resection specimens, extensive extramural invasion was
identified on preoperative MR images. CONCLUSION: Preoperative thin-section MR
imaging accurately indicates the tumor stage of rectal cancer and depth of
extramural tumor infiltration. It provides valuable information for identifying
T3 tumors for preoperative adjuvant therapy in patients who are at high risk of
failure of complete excision.
PMID- 10189475
TI - Evacuation proctography: a prospective study of diagnostic and therapeutic
effects.
AB - PURPOSE: To determine the diagnostic and therapeutic effects of evacuation
proctography. MATERIALS AND METHODS: Forty-seven referring clinicians completed
preevacuation proctography questionnaires for 50 patients, detailing diagnoses,
confidence in these, intended management, and what they hoped to learn. After
evacuation proctography, the radiology report was returned with a second
questionnaire asking the diagnosis in the light of evacuation proctographic
findings, their confidence, and what they had learned. Clinicians quantified
management contribution and indicated how useful they found evacuation
proctography in general. Results from pre- and post-evacuation proctography
questionnaires were compared to determine the diagnostic and therapeutic effects.
RESULTS: Diagnostic confidence rose significantly after evacuation proctography
(mean, 7.0 before evacuation proctography vs 8.4 after evacuation proctography; P
< .001). Lead diagnosis changed in nine (18%) patients. Intended surgical
management became nonsurgical after evacuation proctography in seven (14%)
patients, and intended nonsurgical therapy became surgical in two (4%). Surgery
remained likely in 15 patients, but its nature changed in five (10%). Five (10%)
clinicians stated that evacuation proctographic findings resolved diagnostic
conflict, and nine (18%) found that evacuation proctographic findings revealed
unsuspected diagnoses. Clinicians found evacuation proctography of major benefit
in 20 (40%) cases studied and of moderate benefit in 20 (40%). In general, 20
(43%) clinicians found evacuation proctography very useful and 24 (51%) found it
moderately useful. CONCLUSION: Evacuation proctography has a substantial
diagnostic and therapeutic effect and is of considerable benefit to referring
clinicians.
PMID- 10189476
TI - Liver disease in children with cystic fibrosis: US-biochemical comparison in 195
patients.
AB - PURPOSE: To determine if abnormal liver architecture at ultrasonography (US) is
related to abnormal function in children with cystic fibrosis (CF). MATERIALS AND
METHODS: For 1 year, all 195 children (112 boys, 83 girls; mean age, 8.5 years)
attending a CF clinic underwent abdominal US and a standard set of liver function
tests. Aspartate aminotransferase, alanine aminotransferase, and gamma
glutamyltransferase levels were analyzed. US signs were interpreted as follows:
hypoechogenicity with prominent portal tracks as edema, hyperechogenicity as
steatosis, and increased attenuation and nodules within or at the edge of the
liver as cirrhosis. Signs of portal hypertension also were sought. US signs were
compared with liver function test results. RESULTS: Liver sonograms were abnormal
in 38 children (19%); of these, 24 (63%) had abnormal test results. The 157
children with normal liver architecture had a much lower prevalence of
biochemical abnormality (33 patients [21%]; P < or = .001). All eight children
with signs of portal hypertension had abnormal test results. Fourteen (82%) of 17
children with signs of cirrhosis had abnormal liver function. Eight (57%) of 14
patients with signs of steatosis had abnormal function. Diffuse hypoechogenicity
of the liver with prominent portal tracks in 16 patients was associated with
abnormal function in only five patients. CONCLUSION: The relation between
abnormal liver architecture at US and results of three liver function tests in
children with CF was significant. The most specific US abnormalities related to
abnormal function are signs suggestive of portal hypertension and cirrhosis.
PMID- 10189477
TI - Chronic avulsive injury of the deltoid insertion in adolescents: imaging findings
in three cases.
AB - The clinical and imaging (magnetic resonance [MR] imaging, radiography, and bone
scintigraphy) findings in three adolescent boys with chronic avulsive injury at
the deltoid insertion are presented. MR imaging enabled the exclusion of findings
suggestive of malignancy and the localization of abnormalities to the deltoid
insertion site. Findings included cortical thickening and irregularity of the
deltoid tubercle, with or without adjacent soft-tissue edema.
PMID- 10189478
TI - Incomplete intertrochanteric fractures: imaging features and clinical management.
AB - PURPOSE: To present the imaging findings and treatment options for incomplete
intertrochanteric fractures. MATERIALS AND METHODS: Among 31 patients with the
magnetic resonance (MR) imaging diagnosis of incomplete intertrochanteric
fracture, 30 also underwent radiography. MR and radiographic findings were
compared. Note was made of fracture length and extent as depicted on the coronal
and axial MR images, treatment (surgical vs conservative), and follow-up.
RESULTS: Correlation between radiographic and MR findings was poor. Incomplete
intertrochanteric fracture was the prospective radiographic diagnosis in only one
case. Fracture in 18 patients was treated surgically and in 13 was managed
conservatively. In both groups, the average age of the patients and length of the
fractures and the percentage of separate fractures involving the greater
trochanter and crossing the midline of the femur in the axial plane were the
same. Fractures crossed the midline in the coronal plane in 50% of the surgical
group but in only 23% of the nonsurgical group. Average time from injury to
ambulation was 2 days less in the surgical group, but no difference in functional
status was found subjectively between the two groups at clinical follow-up.
CONCLUSION: Incomplete intertrochanteric fractures are a previously unrecognized
subset of intertrochanteric fractures that are diagnosed unequivocally only with
MR imaging.
PMID- 10189479
TI - Muscle infarction in patients with diabetes mellitus: MR imaging findings.
AB - PURPOSE: To describe the magnetic resonance (MR) imaging findings in diabetic
patients with muscle infarction and to describe commonly associated clinical
features. MATERIALS AND METHODS: The MR imaging studies of 21 patients with
diabetic muscle infarction were reviewed retrospectively. Of the 21 patients, 12
were women, and nine were men; the mean age was 48 years (range, 30-77 years).
RESULTS: Eight patients had bilateral lower-extremity involvement; six had
involvement confined to the right lower extremity and seven to the left. The
thigh was involved in 17 patients (81%). One or more of the musculi vastus, the
most frequently affected muscle group, were affected in 16 patients (76%). Four
patients (19%) had isolated calf involvement. MR imaging studies showed diffuse
enlargement of involved muscle groups and partial loss of normal fatty
intermuscular septa. MR imaging also allowed identification of areas of
subfascial fluid in 16 patients (76%) and subcutaneous edema in 19 patients
(90%). MR imaging showed involved muscle groups best with T2-weighted, inversion
recovery, and gadolinium-enhanced sequences, where the infarcted muscles appeared
diffusely hyperintense compared with adjacent muscles. Comparison of T2-weighted
and gadolinium-enhanced MR images of nine patients showed enlarged, enhancing
muscles in all patients and small, focal, rim-enhancing fluid collections in six
of nine patients (66%). CONCLUSION: Diabetic muscle infarction is suggested in
diabetic patients with sudden onset of severe pain in the thigh or calf muscles
who have MR imaging findings of diffuse edema and swelling of multiple thigh and
calf muscles (often in more than one compartment).
PMID- 10189480
TI - Germ cell tumor: differentiation of viable tumor, mature teratoma, and necrotic
tissue with FDG PET and kinetic modeling.
AB - PURPOSE: To evaluate the feasibility of positron emission tomography (PET) with 2
[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) in patients with germ cell tumor
(GCT) to monitor treatment and differentiate residual masses after chemotherapy.
MATERIALS AND METHODS: Twenty-six FDG PET studies were performed in 21 patients
with GCT, FDG uptake of tumors was interpreted visually, and the lean
standardized uptake value (SUVlean) was determined. Tumor kinetic rate constants
(K1, k2, k3) and net rate of FDG phosphorylation (K = [K1.k3]/[k2 + k3]) in
tumors were calculated from the dynamic data by means of a three-compartment
model, assuming k4 = 0. RESULTS: Viable tumors (n = 10) showed intense FDG uptake
and could easily be differentiated visually from mature teratoma (n = 6) and
necrosis or scar (n = 10). The SUVlean of residual viable tumors (4.51 +/- 1.34
[mean +/- SD]) was higher than that of mature teratoma (1.38 +/- 0.71) and
necrosis or scar (1.05 +/- 0.29) (P < .05). Although neither the visual
interpretation nor SUVlean differentiated mature teratoma from necrosis or scar,
there were statistically significant differences in the kinetic rate constants K1
and K between mature teratoma and necrosis or scar as follows: K1, 0.113 mL/min/g
+/- 0.026 versus 0.036 mL/min/g +/- 0.005 (P < .05); K, 0.005 mL/min/g +/- 0.003
versus 0.0008 mL/min/g +/- 0.0001 (P < .05). CONCLUSION: FDG PET with kinetic
analysis appears to be a promising method for management of disease in patients
with GCT after treatment.
PMID- 10189481
TI - Brain: gadolinium-enhanced fast fluid-attenuated inversion-recovery MR imaging.
AB - PURPOSE: To determine the clinical utility of gadolinium-enhanced fluid
attenuated inversion-recovery (FLAIR) magnetic resonance (MR) imaging of the
brain by comparing results with those at gadolinium-enhanced T1-weighted MR
imaging with magnetization transfer (MT) saturation. MATERIALS AND METHODS: In
105 consecutive patients referred for gadolinium-enhanced brain imaging, FLAIR
and T1-weighted MR imaging with MT saturation were performed before and after
administration of gadopentetate dimeglumine (0.1 mmol per kilogram of body
weight). Pre- and postcontrast images were evaluated to determine the presence of
abnormal contrast enhancement and whether enhancement was more conspicuous with
the FLAIR or T1-weighted sequences. RESULTS: Thirty-nine studies showed
intracranial contrast enhancement. Postcontrast T1-weighted images with MT
saturation showed superior enhancement in 14 studies, whereas postcontrast fast
FLAIR images showed superior enhancement in 15 studies. Four cases demonstrated
approximately equal contrast enhancement with both sequences. Six cases showed
some areas of enhancement better with T1-weighted imaging with MT saturation and
other areas better with postcontrast fast FLAIR imaging. Superficial enhancement
was typically better seen with postcontrast fast FLAIR imaging. CONCLUSION: Fast
FLAIR images have noticeable T1 contrast making gadolinium-induced enhancement
visible. Gadolinium enhancement in lesions that are hyperintense on precontrast
FLAIR images, such as intraparenchymal tumors, may be better seen on T1-weighted
images than on postcontrast fast FLAIR images. However, postcontrast fast FLAIR
images may be useful for detecting superficial abnormalities, such as meningeal
disease, because they do not demonstrate contrast enhancement of vessels with
slow flow as do T1-weighted images.
PMID- 10189482
TI - Carotid arteries: maximizing arterial to venous contrast in fluoroscopically
triggered contrast-enhanced MR angiography with elliptic centric view ordering.
AB - PURPOSE: To obtain high-spatial-resolution, venous-suppressed, contrast material
enhanced, three-dimensional (3D) magnetic resonance (MR) angiograms of the
carotid arteries and aortic arch by using an elliptic centric view ordering with
MR fluoroscopic triggering. MATERIALS AND METHODS: Forty consecutive patients
with cerebrovascular disease in the differential diagnosis were evaluated with
fluoroscopically triggered 3D MR angiography (gadoteridol dose range, 0.1-0.3
mmol per kilogram of body weight; mean acquisition time, 40 second +/- 8 [SD]).
The contrast-enhanced 3D MR angiograms were evaluated for overall quality,
vascular signal intensity, venous suppression, and motion artifact. Twenty
patients also underwent two-dimensional (2D) time-of-flight (TOF) MR angiography.
The overall quality of the 2D TOF MR angiograms and comparative quality between
the 2D TOF and contrast-enhanced 3D MR angiograms were determined. RESULTS: The
contrast-enhanced 3D MR angiograms were of excellent or more than adequate
quality for diagnosis in 36 of the 40 studies (90%). In 35 of the 38 contrast
enhanced 3D studies in which the contrast material bolus was detected
fluoroscopically, the internal jugular vein signal intensity was either not
detectable or barely visible. In 18 of the 20 patients who also underwent 2D TOF
MR angiography, the quality of the contrast-enhanced 3D MR angiograms was graded
as markedly superior or superior. CONCLUSION: Contrast-enhanced, elliptic centric
3D MR angiography with real-time MR fluoroscopic triggering offers high-spatial
resolution images of the carotid arteries and aortic arch with reliable venous
suppression.
PMID- 10189483
TI - Thermoacoustic CT with radio waves: a medical imaging paradigm.
AB - The authors evaluated images obtained with a prototypic thermoacoustic computed
tomographic (CT) scanner constructed for use at 434 MHz, a promising radio
frequency for detecting breast cancer. In one excised porcine kidney, acoustic
energy emanating from the kidney was detected with transducers. The resultant
electric signals were used to create a three-dimensional data set. Two
dimensional images reconstructed in multiple planes were compared with state-of
the-art T1- and T2-weighted magnetic resonance images. The renal outline,
parenchyma, and collecting system were clearly delineated on the thermoacoustic
CT images.
PMID- 10189484
TI - Test object for measurement of section thickness at US.
AB - A simple phantom was used to test the ultrasound beam profile in the elevation
direction (perpendicular to the scanning plane). Based on the inclined plane
method, the phantom allowed direct clear display of the section thickness over
the whole exploration depth on a single standard ultrasonographic image. This was
demonstrated with one- and one and one-half-dimensional arrays. The results
showed the efficiency of electronic focusing in the elevation plane associated
with one and one-half-dimensional arrays.
PMID- 10189485
TI - Abdominal fat: standardized technique for measurement at CT.
AB - The authors estimated abdominal fat distribution on the basis of measurements at
computed tomography (CT). The attenuation range for fat tissue was defined as the
interval within the mean plus or minus 2 SDs considered to be individual
variation. Fat areas found with this method were closely correlated with those
obtained by means of the computed planimetric method or with a fixed attenuation
range from -190 to -30 HU as the standard of reference. Although the average CT
numbers obtained with different scanners were distributed widely, the calculated
fat areas were almost identical. This method might be a practical and
standardized method at CT.
PMID- 10189486
TI - Why not optimism?
PMID- 10189487
TI - Coronary artery calcium.
PMID- 10189488
TI - Chest US in the diagnosis of acute pulmonary embolism.
PMID- 10189489
TI - MR imaging in Guillain-Barre syndrome.
PMID- 10189490
TI - Whose Aunt Minnie?
PMID- 10189491
TI - The extent of drilling in lateral approaches to the cranio-cervical junction area
from a series of 125 cases.
AB - The trans-condylar approach to the craniocervical junction area (CCJA) requires a
more or less extensive drilling of the two first cervical joints (C0-C1 and C1
C2). The extent of drilling necessary to resect a lesion at the CCJA was analyzed
from a series of 125 cases including 114 tumours and 11 non-tumoural processes
treated using a lateral approach (postero-lateral or antero-lateral) over a 15
year period (1980-1995). The extent of drilling was estimated on CT scanner axial
views from the reduction of the joints surface and three groups were determined:
A/less than one third B/between one third and one half, and C/more than one half.
The extent of drilling was compared with the lesion location in relation to the
bone limits of the CCJA: within these limits, outside them and into the bony
structures. It was also analyzed with regard to pathology when separated into
three groups non-osseous tumours, osseous tumours and chordomas, and non tumoural
processes. Only 26 cases had a significant drilling, i.e., more than one third of
the joint surfaces and of these, 14 were more than one half. In all these 14
cases, the bone structures were already invaded and 13 of them were, to some
extent, beyond the bone limits of the CCJA. Of the 12 cases with drilling between
one third and one half, 11 involved the bone structures and 1 was located inside
the CCJA bone limits. Drilling of more than one third was required only in the
case of bone lesions: 10 out of 23 bone tumours, all the 14 cases of chordomas,
one case of rheumatoid arthritis and one case of C1-C2 joint spondylosis. In the
other cases including mostly non-osseous tumours, drilling was limited to less
than one third, though a high rate of complete removal was achieved (98%).
Stabilization by arthrodesis with posterior grafting (N = 10) or by lateral bone
grafting (N = 5) was achieved in all cases involving more than one half drilling,
and in one case of tuberculosis. By adequately choosing the surgical approach,
the extent of drilling can always be minimal. Extensive bone resection is only
necessary when the tumour has already destroyed the joints. In that case, lateral
or posterior fusion is an efficient technique.
PMID- 10189492
TI - High cervical disc lesions in elderly patients--presentation and surgical
approach.
AB - The incidence of high cervical disc lesions is extremely rare, and the mechanism
of their development is unclear. We report these three cases, and discuss the
possible mechanisms. We also describe surgical strategies for these lesions. The
first and second cases were an 82-year-old male and an 84-year-old male with
retro-odontoid disc hernia. The third was an 83-year-old female with a herniated
disc at C2/C3. To investigate Aetiological mechanisms of these lesions, we
examined the findings on cervical images in extension and flexion, and compared
the results in a younger than 80-year-old group and an older than 80-year-old
group. The patients underwent surgery via a posterolateral intradural approach.
Wide laminectomy and incision of the dentate ligaments enabled access to the
ventral space of the upper cervical spinal canal and sufficient decompression.
All patients became ambulatory postoperatively without special fixation of the
cervical spine. In the younger group, the level mostly loaded during cervical
movement was C5/6, however, the levels in the older group were C2/3 and C3/4. In
elderly patients, less mobilization of the middle and/or lower cervical spine due
to spondylotic change causes overloading at higher levels resulting in high
cervical disc lesions. Retro-odontoid disc lesions can be caused by a herniated
disc at C2/C3, which migrates upward. Regarding surgical strategy, the
posterolateral intradural approach is less invasive and more advantageous for
these lesions.
PMID- 10189493
TI - Intracavity fractionated balloon brachytherapy in glioblastoma.
AB - In order to reduce hospitalisation time for patients receiving postoperative
radiotherapy a phase I-II study of intracavity balloon brachytherapy was
instituted. An indwelling balloon catheter was implanted during the closing phase
of the initial operation. Starting on the second or third postoperative day the
catheter was afterloaded with a high dose rate isotope via a remotely controlled
afterloading system. The treatment consisted of 10-12 fractions over a period of
5-6 days, with each treatment session requiring approximately 15 minutes. No
external beam radiation was given. Forty-four newly diagnosed patients were
treated. A total dose of either 60 Gy (33 patients) or 72 Gy (11 patients) was
given. The overall median survival was 11.7 months, (range 2.7-50.9). The
treatment was well tolerated and none of the applicators were removed
prematurely. The total median hospital stay for this group of patients was
significantly reduced compared to more conventional protocols. This study
indicates that intracavity high dose rate balloon brachytherapy can achieve
survival rates equivalent to those of conventional radiotherapy and is both cost
and time efficient.
PMID- 10189494
TI - Cerebral gangliogliomas: clinical characteristics, CT and MRI.
AB - Eight patients with ganglioglioma who received surgical treatment at our
institute between January 1989 and January 1997 were reviewed to determine their
clinical, CT and MRI characteristics. Tumours were located in the temporal lobe
(four patients), trigone of the lateral ventricle (two patients), basal ganglia
(one patient) and fronto-temporal lobe (one patient). On imaging, two types of
tumours were seen, a solid mass in 5 patients (62.5%) and a cystic mass in three
patients (37.5%). Six complete tumours (75%) and all of the solid components of
the cystic tumours were enhanced by contrast medium. Seven tumours (88%) had no
peripheral oedema. On CT, the tumours being studied appeared as iso-(62.5%) or
low density (37.5%) intra-axial tumours. Four tumours (50%) contained
calcification. On MRI, the tumours appeared as well-circumscribed, iso-(62.5%) or
low intensity (37.5%) intra-axial tumours on T1 weighted images, and as high
(75%) on T2 weighted images. Three underwent total resection, 2 subtotal
resection and 3 partial resection. No patients had have any further treatment
such as radiation therapy or chemotherapy. Postoperative studies were conducted
on all patients with an average follow-up period 56 months (range 4-147 months)
after surgery. There was no evidence of recurrence of tumours or of growth of
residual tumours. We observed gangliogliomas which were located in unusual
regions such as the trigone in two of the patients. To our knowledge, our series
is the first report to describe trigonal gangliogliomas. We conclude, therefore,
that ganglioglioma should be included as a possibility in the differential
diagnosis of intracranial masses, even when they are located in the trigone.
PMID- 10189496
TI - Bleeding risk in unruptured and residual cerebral aneurysms--angiographic annual
growth rate in nineteen patients.
AB - Whether and when unruptured aneurysms or aneurysmal rests following incomplete
surgery result in subsequent bleeding are major concerns for neurosurgeons. By
calculating the annual growth rate of aneurysms in long-term follow-up
angiography (partly supplemented with MR-imaging and/or MR-angiography), we
attempted to determine the surgical indications for these aneurysms. Long-term
follow-up angiography ranging from one to 20 years was carried out on five
patients whose ruptured aneurysms had been incompletely occluded, six patients
with multiple aneurysms, of which the ruptured ones had been completely
obliterated at operation and the small unruptured aneurysms, missed or
misdiagnosed, and eight patients with unruptured aneurysms which were
asymptomatic or symptomatic. The correlation of annual aneurysm growth rate to
subsequent bleeding was investigated. Four out of six fast-growing aneurysms with
high annual growth rates (more than 8% increase per year) resulted in subsequent
bleeding whereas none of the fourteen slow-growing aneurysms with low annual
growth rates (less than 8% increase per year) led to bleeding (Fisher's exact
test; p < 0.01). Hypertension, patient age and aneurysmal location showed no
significant correlation to the annual growth rate (Fisher's exact test; p >
0.05). This study suggests that aneurysmal rests after incomplete surgery and
missed or misdiagnosed multiple or incidental aneurysms which are fast growing
have a high possibility of subsequent bleeding and should be operated on as soon
as possible.
PMID- 10189495
TI - Localization and characterization of intracerebral cavernous angiomas by intra
operative high-resolution colour-duplex-sonography.
AB - The aim of this prospective study was to evaluate the reliability of high
resolution Colour-Duplex-Sonography (= CDS) in intra-operative localization,
guiding and characterization of intracerebral cavernous angiomas (= CA). During a
time period from 5/93 to 12/96 a total of 26 patients with 21 supratentorial and
5 infratentorial CA (15 of them deep-seated) were examined intra-operatively by
CDS. The study focussed on 1. sonographic characterization, 2. localization in
relationship to anatomical landmarks, 3. navigation, 4. correlation of
sonographic to magnetic resonance imaging (= MRI), intra-arterial angiography (=
DSA) and histological results and 5. control of complete resection. All CA
appeared sonographically as hyperechoic lesions without flow-signals in Colour
mode. Imaging of anatomical landmarks as cerebral sulci, brain stem, insular
cistern, falx, ventricles and vessels could be used for precise localization and
successful guiding to 15 deep-seated lesions. The correlation of the size between
MRI and CDS was excellent (1.4 mm mean difference, range from 0 to 5 mm). All 4
associated venous anomalies, as verified by pre-operative DSA, could be
visualized and identified by CDS. The completeness of exstirpation was controlled
sonographically in 14 cases and confirmed by MRI (= 10) and CT (= 4). This study
provides the first comprehensive intra-operative characterization of CAs by CDS
and correlation to MRI and DSA. Furthermore it demonstrates the reliability of
CDS for intra-operative localization and guiding as well as its potential to
control the complete exstirpation.
PMID- 10189497
TI - Advantage of intravenous anaesthesia for acute stage surgery of aneurysmal
subarachnoid haemorrhage.
AB - To investigate the clinical effects of intravenous anaesthesia on surgical
procedure and the outcome in acute stage surgery for aneurysmal subarachnoid
haemorrhage (SAH), pre-, intra-, and post-operative factors were analyzed to
compare between inhalational (IA, n = 38) and intravenous (IVA, n = 37)
anaesthesia. IVA significantly shortened the duration of surgery (p < 0.05) and
the duration of hospital stay (p < 0.01). These results suggest that IVA may be
more suitable than IA for acute stage surgery of aneurysmal SAH. These effects
may be mainly caused by IVA's pharmakokinetics, by effects on intracranial
homeostasis and metabolism, and neuroprotective properties.
PMID- 10189498
TI - Delayed postoperative CSF rhinorrhea of intrasellar arachnoid cyst.
AB - CSF rhinorrhea due to a transsphenoidal approach usually follows accidental or
intentional arachnoid opening. We report a patient with an intrasellar arachnoid
cyst, who developed delayed onset of CSF rhinorrhea. A sixty-two-year-old man
presented with bitemporal type visual field defect for the last 3 years. With the
diagnosis of arachnoid cyst or Rathke's cleft cyst, based on MRI findings of
intra-and supra-sellar cyst with CSF intensity, he successfully underwent
transsphenoidal surgery without evidence of intra-operative CSF leakage. He
developed CSF rhinorrhea one week later. This needed another operation for sellar
floor repair. The pathomechanism of this delayed onset is explained as follows.
Incomplete or oneway communication of subarachnoid space to cyst cavity,
unrecognized during surgery, might cause delayed onset of CSF rhinorrhea. By
using MRI, identification of the residual gland, which was compressed
posteriorly, is useful for differentiating an arachnoid cyst from other cystic
lesions. In highly suspect cases, even without evidence of intra-operative CSF
leakage, peri-operative measures to prevent occurrence of postoperative CSF
rhinorrhea are required.
PMID- 10189499
TI - Burr hole evacuation of chronic subdural haematomas followed by continuous inflow
and outflow irrigation.
AB - Chronic subdural haematomas are prone to recollect, increasing the risk of
further complications and death. Burr hole evacuation followed by continuous
irrigation of a Ringer solution into the remaining subdural cavity, allows
remaining blood to be washed out and the brain to re-expand. This technique was
compared with burr hole evacuation either without or with a passive drainage and
craniotomy, respectively. Reformation of haematomas after continuous irrigation
occurred in 2.6% (2/77); more than a twelve (32.6%; 15/46) and a nine (23.8%;
5/21) times rate reduction compared to burr hole evacuation without and with
passive drainage, respectively. Compared to the craniotomy results, the rate
dropped seventeen times (44.4%; 4/9). Expect from the two rebleedings in 77
haematomas operated on through burr holes followed by irrigation, all patients
recovered including nine recurrent haematomas re-operated on by this method.
Recurrent haematomas operated on through burr hole evacuation alone or with
insertion of a passive drainage, recollected in 50% (2/4) and 33.3% (2/6).
Similar rate after craniotomies was 11.1% (1/9). Neither infections nor deaths
followed burr hole evacuation combined with continuous irrigation, whereas 5.3%
(2/38) and 5.9% (1/17) suffered from empyema after burr hole evacuation alone or
combined with a passive drainage, respectively. Five (9.1%) of these 55 patients
died either from empyemas (three) or rebleedings (two). Recurrent haematomas
evacuated through a craniotomy had no complications from infections. Compared to
other methods, continuous irrigation reduces the need for re-operation
significantly by preventing haematoma recurrence and empyema formation. Contrary
to other surgical techniques, haematoma recurrence after second time surgery did
not occur.
PMID- 10189500
TI - Local coagulofibrinolysis in the postsurgical recovery of patients with chronic
subdural haematoma.
AB - Postoperative recovery of patients with chronic subdural haematoma (CSH) was
investigated by comparing pre- and postoperative coagulant and fibrinolytic
activity in the haematoma contents of 15 patients with SCH. Patients in this
study were treated draining the haematoma cavity without irrigation, a procedure
dubbed the closed drainage. Haematomas were collected during, and 24 hrs after,
surgery. Postoperative fibrinolytic activity was lower than that observed pre
operatively. In particular, levels of tissue plasminogen activator activity
(TPA), and fibrin and fibrinogen degradation products (FDP) all decreased. In
contrast, coagulant activity increased postoperatively. This paper will discuss
the role of local coagulofibrinolysis in the postoperative recovery of CSH
patients.
PMID- 10189501
TI - A new bone dust packer for use in neurosurgery.
AB - A new tool for the packing of bone dust has been developed. The instrument
compresses a mixture of bone dust and saline into suitable cylindrical plugs,
fitting neatly into craniotomy burrholes. The skullbone at the craniotomy area
will heal neatly also assuring the best healing possibilities for the overlying
skin. The cosmetic results are excellent as no skin dents or cavities will be
formed over the burrholes.
PMID- 10189502
TI - Expression of P27kip1 and Ki-67 in pituitary adenomas: an investigation of marker
of adenoma invasiveness.
AB - Mirroring the ambiguities noted with other endocrine tumours, histology is a poor
predictor of the invasiveness of pituitary adenomas. Accordingly, the proteins
p27Kip1 (p27) and Ki-67, which respectively block cell-cycle progression and
reflect proliferative activity of cells, were studied immunohistochemically in
123 specimens of pituitary adenomas including 57 clinically verified invasive
cases. Only Ki-67 had a significant association with invasiveness; only p27
differed significantly between functioning and nonfunctioning adenomas, with a
higher frequency of cell labelling in the former. No relationship between Ki-67
and p27 was obtained. Ki-67 detected by MIB-1 is thus an important marker related
to the invasive potential of adenomas, and thereby may be helpful in planning
postoperative management of patients with pituitary adenomas.
PMID- 10189503
TI - Behavioural and morphological outcome of mild cortical contusion trauma of the
rat brain: influence of NMDA-receptor blockade.
AB - The authors studied the effect of a mild cortical contusion to the rat brain on
behavioural and morphological outcome and the influence of NMDA-receptor blockade
(MK-801, 0.5 mg/kg i.v. 30 min prior to trauma). Spontaneous motor activity was
assessed 16-18 days post trauma. Saline treated traumatised rats showed a
significant (p < 0.01) hyperactive behaviour compared to animals without injury.
MK-801 treated rats performed significantly better than the saline treated
animals (p < 0.05). For histopathological evaluation hippocampal hilar neurons
were counted, cortical thickness under the impact was measured and microtubule
associated protein 2 (MAP2) immunoreactivity in the dentate hilus was quantified
1, 3 and 21 days post trauma. In traumatised rats scattered loss of nerve cells,
oedema and minute haemorrhages were present at the site of the impact one and
three days after injury. At day 21 there was a significant reduction of cortical
thickness at the site of impact. One day after trauma there was a bilateral,
significant loss of neurons and MAP2 immunostaining in the dentate hilus of the
hippocampus. MK-801 pretreated rats showed similar morphological changes. The
disturbed spontaneous motor behaviour may be caused by hippocampal damage and a
reduction of somatosensory cortical neurons. NMDA-receptor blockade improved the
outcome assessed by the functional tests but failed to influence the
morphological changes, suggesting that this behavioural test is a more sensitive
indicator of outcome after mild traumatic brain injury (TBI).
PMID- 10189504
TI - Polyostotic fibrous dysplasia with craniofacial localization presenting with
frontal lobe compression in a 14-year-old girl.
AB - We describe a rare case of polyostotic fibrous dysplasia with craniofacial
localization associated with involvement of the spine and extremities. A 14-year
old girl presented with progressive headache, left frontal swelling, exophthalmos
of the left eye, deformity and palpable mass in the left frontal area. Cranial
computerized tomography revealed extensive involvement of all cranial bones
except right frontal and right parietal bones. Most of the facial bones were
invaded. Especially, there was the involvement of ethmoidal air sinuses and
frontal sinus also. Computerized tomography showed left frontal lobe compression.
In addition, the spine and bones of the extremities were involved in the patient.
Craniofacial approach was planned. Cranial surgery was performed by an extradural
frontal approach. Firstly, the frontal cyst was excised. For left frontal lobe
decompression, we removed successfully all the abnormal bones causing mass effect
and frontal deformity. Secondly, facial surgery was performed with external
approach. An attempt to remove all of the involved bone is necessary, as the
lesion may recur and grow if a portion of dysplastic bone is left in place.
However, the present case suggests that removal of all the involved bones in the
polyostotic fibrous dysplasia may be possible in spite of extensive involvement.
In this situation, it may be removal of only abnormal bones responsible for
compression of affected neural elements is indicated.
PMID- 10189505
TI - Transient mutism resolving into cerebellar speech after brain stem infarction
following a traumatic injury of the vertebral artery in a child.
AB - A 3.7-year-old girl presented with an anterior neck injury followed by
progressive subcutaneous emphysema and loss of consciousness. After
resuscitation, a laceration on the first tracheal cartilage was closed
surgically. As she was extubated one week later, she was found to have right
hemiplegia and muteness. MRI showed a T2-bright lesion on the tegmentum of the
left midbrain down to the upper pons. Right vertebral angiography disclosed an
intimal flap with stenosis at the C3 vertebral level presumably caused by a
fracture of the right C3 transverse process later confirmed in a cervical 3D-CT
scan. Her muteness lasted for 10 days, after which she began to utter some
comprehensible words in a dysarthric fashion. Her neurological deficits showed
improvement within 3 months of her admission. Transient mutism after brain stem
infarction has not been reported previously. We discuss the anatomical bases for
this unusual reversible disorder in the light of previous observations and
conclude that bilateral damage to the dentatothalamocortical fibers at the
decussation of the superior cerebellar peduncle may have been responsible for her
transient mutism.
PMID- 10189506
TI - Spinal cord compression by a metastasizing thymoma.
PMID- 10189507
TI - Cerebellar abscess due to Nocardia asteroids.
PMID- 10189508
TI - Solitary plasmacytoma of the pituitary area.
PMID- 10189509
TI - Substance abuse history predicts depression and relapse status among cocaine
abusers.
AB - This study examined the relationships between lifetime years of cocaine, alcohol,
and marijuana use prior to entry into residential treatment for primary cocaine
dependence and (a) intake depression levels, and (b) levels of cocaine use in the
six months after completing treatment. Years of education, age, and lifetime
years of cocaine and alcohol use contributed significantly to predicting
depression levels. Lifetime years of alcohol use alone predicted cocaine use
during the six months post-treatment.
PMID- 10189510
TI - Alcohol use in adolescent females: correlates with estradiol and testosterone.
AB - This study investigated if self-reports of alcohol use correlated with estradiol
and testosterone levels in adolescent females. Ninety-four female senior high
school student volunteers from 2 schools completed a questionnaire regarding
alcohol use. Twenty cc of blood was assayed for estradiol, testosterone,
progesterone, and FSH. Total estradiol levels were higher in females who reported
current alcohol use (p < or = 0.05), and females with higher levels of both
testosterone and estradiol were more likely to be using alcohol currently (p < or
= 0.05). Hormonal relationships associated with adolescent alcohol use may be
related to future health risks of alcohol use and/or increased risk of alcohol
use.
PMID- 10189511
TI - The relationship between parental history and substance use severity in drug
treatment patients.
AB - The authors explored the relationship between the history of parental problematic
alcohol and drug use and their adult children's alcohol and drug use disorders.
Subjects were 347 admissions to an outpatient substance abuse program. There was
a positive relationship between the number of parents affected by alcohol and/or
drug problems and the percentage of probands with co-existing alcohol and drug
use disorders for probands with alcohol use disorders but not for those with only
drug abuse. Probands with two affected parents had significantly higher alcohol
abuse scores and drug, family, and psychiatric composite test scores than those
with a negative family history. This preliminary study indicates that the
severity of a proband's substance use disorder may be influenced by parental
substance use history.
PMID- 10189512
TI - Antisocial alcoholic patients show as much improvement at 14-month follow-up as
non-antisocial alcoholic patients.
AB - The authors investigated the impact of DSM-III-R adult criteria for antisocial
personality disorder (and co-occurrence of childhood conduct or mood disorder) on
one-year changes of multi-domain problem severity in 309 alcoholic patients.
Adult antisocial traits were associated with more drug, legal, and psychiatric
problems at baseline and with more drug problems at follow-up. However, patients
with antisocial traits showed at least as much improvement from baseline through
follow-up as their non-antisocial counterparts. Furthermore, the co-occurrence of
childhood conduct disorder or mood disorder among the antisocial alcoholics did
not define prognostically relevant subgroups. These findings suggest that
antisocial alcoholics benefit from treatment at least as much as non-antisocial
alcoholics.
PMID- 10189513
TI - Residential treatment for dually diagnosed homeless veterans: a comparison of
program types.
AB - This study compared two types of residential programs that treat dually diagnosed
homeless veterans. Programs specializing in the treatment of substance abuse
disorders (SA) and those programs addressing both psychiatric disorders and
substance abuse problems within the same setting (DDX) were compared on (1)
program characteristics, (2) clients' perceived environment, and (3) outcomes of
treatment. The study was based on surveys and discharge reports from residential
treatment facilities that were under contract to the Department of Veterans
Affairs Health Care for Homeless Veterans program, a national outreach and case
management program operating at 71 sites across the nation. Program
characteristics surveys were completed by program administrators, perceived
environment surveys were completed by veterans in treatment, and discharge
reports were completed by VA case managers. DDX programs were characterized by
lower expectations for functioning, more acceptance of problem behavior, and more
accommodation for choice and privacy, relative to SA programs after adjusting for
baseline differences. Dually diagnosed veterans in DDX programs perceived these
programs as less controlling than SA programs, but also as having lower
involvement and less practical and personal problem orientations. At discharge, a
lower percentage of veterans from DDX than SA programs left without staff
consultation. A higher percentage of veterans from DDX than SA programs were
discharged to community housing rather than to further institutional treatment.
Program effects were not different for psychotic and non-psychotic veterans.
Although differences were modest, integration of substance abuse and psychiatric
treatment may promote a faster return to community living for dually diagnosed
homeless veterans. Such integration did not differentially benefit dually
diagnosed veterans whose psychiatric problems included a psychotic disorder.
PMID- 10189514
TI - Effect of gender, treatment site and psychiatric comorbidity on quality of life
outcome in substance dependence.
AB - Patients receiving treatment for substance dependence frequently endorse high
rates of psychological impairment and other measures of reduced quality of life.
We conducted a baseline and six-month follow-up study of a series of one hundred
and three unselected patients receiving treatment for a substance abuse or
dependence problem. Women and patients requiring in-patient detoxification
demonstrated the most psychological impairment at baseline, as measured by the
mental component summary of the SF-36. Inpatient site of treatment was associated
with continued psychological impairment six months following treatment. More
aggressive psychiatric and psychological interventions may be indicated for women
and for inpatient substance dependence populations.
PMID- 10189515
TI - Course of substance abuse in patients with and without schizophrenia.
AB - The authors compared the course of Substance Use Disorders (SUD) in patients with
SUD plus schizophrenia (SCZ) with those having SUD only. Data were obtained
through diagnostic interviews and questionnaires on consecutive out-patients and
in-patients referred for SUD to two university medical centers with alcohol-drug
programs. This study revealed the SCZ-SUD patients (n = 29) had demographic
characteristics, onset of their substance use, course of use/abuse, and lifetime
SUD diagnoses that closely resembled those with SUD-only (n = 296). The marked
similarities argue for a course of SUD in schizophrenic patients that is fully as
morbid as that in SUD-only patients. The few differences in course appear linked
to the following: (1) patients with SCZ using caffeine early, perhaps to relieve
prodromal manifestations of schizophrenia, (2) patients with SCZ-SUD later using
less or avoiding use of substances that exacerbate symptoms of schizophrenia
(e.g., caffeine, cocaine, opiates), and (3) using tobacco more often to
ameliorate the symptoms of schizophrenia or the side effects of medications used
to treat schizophrenia. Contrary to expectation, those with comorbid SCZ-SUD
employed self-help to deal with SUD as often as did the SUD-only patients.
PMID- 10189516
TI - Changing patterns of illicit substance use among schizophrenic patients: 1984
1996.
AB - Over 1,700 psychiatric emergency room visits of schizophrenic and schizoaffective
patients between 1984 and 1996 were reviewed, and urine drug screens (UDS) were
recorded. Illicit drug use increased significantly over the 12-year period, with
a large increase for cocaine (0% to 73% of positive UDS), a decline for
amphetamines (60% to 0%), and a small increase for marijuana (0% to 27%). Opiate
and sedative use remained unchanged. The results support the impression that
cocaine use increased dramatically among urban schizophrenic patients beginning
in 1988 and continuing to the present. Furthermore, cocaine seems to have
replaced amphetamines as the preferred drug of abuse among schizophrenic persons
following the crack epidemic.
PMID- 10189517
TI - Perceived effects of exercise and sport in a population defined by their
injection drug use.
AB - The role of exercise and sport in the lives of intravenous drug users (n = 45)
was assessed, using an interviewer-administered open-ended questionnaire. Results
demonstrated a high level of exercise and sport interest in this population
(64%). Being a sports fan was also found in most of the responses (72%). This
study on the role of exercise and sport in an intravenous drug-using population
could be considered when developing rehabilitation measures or as an addition to
present therapeutic interventions.
PMID- 10189518
TI - Interactions of cocaine with nimodipine: a brief report.
AB - This double blind, placebo controlled study of acute calcium channel antagonist
use during cocaine administration in five patients found that 60 mg of nimodipine
treatment attenuated the systolic, but not diastolic, blood pressure effects of
cocaine. In three subjects, a 90 mg dose of nimodipine showed a greater
attenuation than that of 60 mg. Subjective effects of cocaine were not altered by
either dose of nimodipine.
PMID- 10189519
TI - [Cellular mechanisms of anesthesia--from unitary theory to nitric oxide mediated
signal transduction].
PMID- 10189520
TI - [The NO/cGMP signal transduction system: a central target for anesthetics?].
AB - The identity and physiologic function of nitric oxide (NO) as an intra- and
intercellular transmitter substance have only been recognized during the last
years. A variety of tissues including neuronal tissue is able to synthesize NO
catalysed by the enzyme NO-synthase. Three isoforms of this enzyme have been
described: the endothelial NO-synthase, the immunologic NO-synthase, and the
neuronal NO-synthase. Within the cell NO binds to a haeme-moiety of the enzyme
guanylyl cyclase thus increasing concentrations of cyclic guanosine monophosphate
(cGMP). The NO metabolism is influenced by volatile as well as intravenous
anaesthetics. The action of inhalational and intravenous anesthetics as well as
other substances with hypnotic properties such as alpha 2-adrenoceptor agonists
has been demonstrated to be increased after disruption of NO-synthase activity by
NO-synthase inhibitors. Different mechanisms of interaction of anaesthetics with
the NO/cGMP signal transduction pathway are conceivable: at the receptor level,
at the NO-synthase, or at the guanylyl cyclase. Common denominator of the NO/cGMP
pathway is the control of cGMP. This second messenger regulates the activity of
protein kinases, phosphodiesterases, and ion channels. However, the relevance of
these structures for the hypnotic-anaesthetic action of general anaesthetics is
currently unclear. Recent findings in mice deficient of neuronal NO-synthase
activity and in animals chronically treated with NO-synthase inhibitors suggest
that in addition to the NO/cGMP-metabolism other signal transduction pathways
exist that are necessary for the action of general anaesthetics.
PMID- 10189521
TI - [Controlling in clinical management].
AB - Managers of industrial enterprises strive continually to improve the efficiency
of production, distribution and service for their customers in order to be able
to compete on the market. In socially orientated non-profit-organisations this is
not universe practice. Relating to section 17 Abs. 1 KHG and section 13 BPfIV of
German social legislation hospital charges are refunded only, if the hospital is
working efficiently and economically. Controlling is a tool to achieve these
goals. Controlling coordinates the flow of information for planning and
evaluation. Strategic and operative controlling are closely interrelated:
Strategic controlling is directed towards new and promising activities, operative
controlling supports decision--making--including future-oriented aspects-by
providing and condensing information. Controlling is definitely not intended to
dictate or "command" any action. Its object is to serve as an instrument or tool
supporting result-oriented planning, regulating and evaluation.
PMID- 10189522
TI - [Visceral resorption of intra-abdominal insufflated carbon dioxide in swine].
AB - OBJECTIVES: Total intraperitoneal carbon dioxide (CO2) resorption from CO2
pneumoperitoneum increases in relation to intraabdominal pressure (IAP) up to an
upper limit of 10 to 15 mmHg. The purpose of this prospective study was to
evaluate the visceral fraction of CO2 resorption in comparison to total
intraperitoneal CO2 resorption in pigs to address possible reasons for this upper
limit. METHODS: 16 pigs were chronically instrumented. Via midline laparotomy, a
transit-time ultrasound flow probe was placed around the portal vein for
continuous recording of the portal venous blood flow and a catheter was inserted
into the portal vein via lienal vein. After complete recovery (7-10 days),
animals were anesthetized with propofol and fentanyl and a pulmonary artery, a
hepatic venous, an arterial, and an intraabdominal insufflation catheter were
inserted. Mechanical ventilation (O2/air; FiO2 = 0.4) was adjusted to maintain
endtidal CO2 at 34 to 36 mmHg using an Engstrom Elvira ventilator. After an
equilibration period of 3h, CO2, (n = 8) or air (n = 8) was insufflated. IAP was
increased in steps of 4 mmHg and maintained constant at each respective IAP-level
for 20 min. Blood gas analyses were assessed from portal venous, hepatic venous,
central venous, and arterial probes at each IAP-level. Total intraperitoneal CO2
resorption was calculated from parameters derived from indirect calorimetry, the
portal venous fraction from blood gas values and the portal venous blood flow
following Fick's principle. Data were analyzed using Friedman's test. RESULTS:
Total CO2 resorption increased continuously with rising IAP. Highest values were
measured at IAP = 16 mmHg with 84 (74-93) ml/min. A further increase of IAP
resulted in a significant decrease of total CO2 resorption. The visceral fraction
of intraperitoneal CO2 resorption increased up to 28 (17-36) ml/min at IAP = 12
mmHg. Portal venous blood flow was also elevated or unchanged up to this IAP. At
IAP = 20 mmHg or IAP = 24 mmHg portal venous blood flow decreased (79% of
baseline) and in consequence portal venous calculated fraction of intraperitoneal
carbon dioxide resorption decreased to 14 (8-20) ml/min. 20 min after
desufflation, intraabdominal CO2 resorption was completed. With air insufflation,
all parameters of CO2 balance were unchanged. DISCUSSION: The IAP dependent
increase in CO2 resorption is limited due to an IAP related occlusion of the
peritoneal capillaries and the limited expansion of peritoneal diffusion area. In
this model, it was possible to show that visceral fraction is about one third of
the total intraperitoneal carbon dioxide resorption and that this fraction
depends on portal venous blood flow. Thus, a decrease in total CO2 resorption may
indicate a reduction in portal venous blood flow.
PMID- 10189523
TI - [Con: patient-controlled analgesia (PCA)].
PMID- 10189524
TI - [Pro: patient-controlled analgesia (PCA)].
PMID- 10189525
TI - [Horizontal deceleration trauma with diffuse decollement bleeding--a casuistry].
AB - Treatment of severe haemorrhage caused by multiple trauma is a serious challenge
to preclinical as well as clinical management. This is a case report of a
motorcycle accident in which a patient sustained total amputation of both legs.
Following adequate preclinical care, vital indication led to the patient's
immediate surgical treatment. After initially successful haemodynamic
stabilisation, the patient developed a horizontal deceleration trauma which
resulted in an extended decollement of the muscles of the back and buttock.
During the further clinical course, soft tissue bleeding occurred that affected
the whole torso. Due to its extent, the bleeding could not be treated surgically,
nor did it allow of haemodynamic stabilisation despite continuous massive
transfusion. Retrospectively, the impressing amputation injury was treated
successfully. In spite of all available surgical and intensive care efforts,
however, the slowly demasking monstrous decollement with diffuse tissue bleeding
proved to be an injury pattern leading to the patient's death.
PMID- 10189526
TI - [Concepts for stroke therapy].
AB - Thrombolytic therapy and "stroke units" are the main new concepts of stroke
therapy that have been recently introduced into clinical practice. Although
thrombolysis decreases the likelihood of disability by about 12% with regard to
increased mortality and a tenfold increase of bleeding complications, debate over
the value of thrombolytic therapy in acute ischaemic stroke continues. Local
intra-arterial application of thrombolytic substances, however, is recommended
for embolic occlusion of the basilar artery, since thrombolytic therapy reduces
mortality in these patients from about 90% to less than 50%. "Stroke units" have
been developed to enable rapid evaluation of stroke patients and to improve
medical care of the patients. Several studies have shown that stroke unit care of
the patients indeed improves outcome with decreased mortality, a better chance of
the patient being discharged to home after hospital stay, shorter length of
hospital stay, as well as fewer medical complications.
PMID- 10189527
TI - [Anesthesia for Cesarean section in Germany in 1997].
PMID- 10189529
TI - The diabetes prevention program.
PMID- 10189528
TI - Insulitis in an autoimmune-mediated patient originally classified as having type
2 diabetes.
PMID- 10189530
TI - Effect of moderate improvement in metabolic control on magnesium and lipid
concentrations in patients with type 1 diabetes.
AB - OBJECTIVE: To evaluate the effect of clinically obtainable improvements in
metabolic control in patients with type 1 diabetes on biochemical cardiovascular
risk factors. RESEARCH DESIGN AND METHODS: Blood and 24-h urinary samples were
obtained from 49 patients with type 1 diabetes before and after a run-in period
and after 3 months of intervention, with frequent adjustment of insulin dosage
according to measured blood glucose concentrations. RESULTS: The intervention
caused a mean insulin dosage increment of 10%, a 20% decrease in fasting plasma
glucose concentration, a 10% decrease in albumin corrected serum fructosamine,
and a somewhat lesser decrease in HbAlc.A 14% decrease in the renal excretion of
magnesium (Mg) was observed, but without a change in average serum Mg
concentration. Serum HDL cholesterol increased 4%, and serum triglycerides
decreased 10% as an average. Looking at individual patients, the decrease in
serum triglycerides correlated with both the change in serum total Mg
concentration and with the increase in insulin dosage. Using the change in serum
total Mg concentration and in insulin dosage as independent variables in a
multiple regression analysis, the coefficient of correlation with the decrease in
serum triglycerides was 0.52. CONCLUSIONS: Moderate but clinically obtainable
improvement of metabolic control in patients with type 1 diabetes seems to reduce
the loss of Mg, increase serum HDL cholesterol, and decrease serum triglycerides.
The decrease in serum triglycerides was associated with the change in serum total
Mg concentration. These reductions in Mg loss and serum triglycerides might
reduce the risk of developing cardiovascular disease in patients with type 1
diabetes.
PMID- 10189531
TI - Effects of regular walking on cardiovascular risk factors and body composition in
normoglycemic women and women with type 2 diabetes.
AB - OBJECTIVE: To examine the impact of a 12-week walking program on body composition
and risk factors for cardiovascular disease in women with type 2 diabetes and in
normoglycemic women with first-degree diabetic relatives. RESEARCH DESIGN AND
METHODS: There were 11 postmenopausal women with type 2 diabetes and 20
normoglycemic women of similar age and BMI who were asked to walk 1 h per day on
5 days each week for 12 weeks. Fitness (estimated VO2max) was assessed with a 1.6
km walking test; body composition was measured by dual-energy X-ray
absorptiometry; and sex hormone, metabolic, and lipid concentrations were
measured in serum. RESULTS: After 12 weeks, estimated VO2max improved in both
groups (P < 0.005). In the diabetic women, BMI and fat content of the upper body
and android waist region decreased (P < 0.05). Concentrations of fasting blood
glucose (P < 0.05) HbAlc (P < 0.05), total cholesterol (P < 0.005), and LDL
cholesterol (P < 0.05) decreased, while HDL cholesterol and sex hormones were
unchanged. In contrast, normoglycemic women failed to lose body fat after 12
weeks of exercise in a walking program. However, their HbAlc, total cholesterol,
LDL cholesterol, sex hormone-binding globulin, and total testosterone
concentrations decreased (P < 0.05). On pooling the data and including diabetes
as a categorical grouping variable, stepwise multiple regression analysis
indicated that the change in centralized body fat, but not the change in VO2max,
was related to change in fasting blood glucose. CONCLUSIONS: Twelve weeks of
walking increased the fitness of diabetic and normoglycemic women. Improvement of
fasting blood glucose was related to the loss of centralized body fat rather than
to improved fitness.
PMID- 10189533
TI - Impact of the work environment on glycemic control and adaptation to diabetes.
AB - OBJECTIVE: To evaluate quantitatively whether the work environments of adults
with diabetes relate to the adequacy of metabolic control and/or to the
individual's adaptation to diabetes and to explore qualitatively the interactions
between an individual's life at work and ways of coping with diabetes. RESEARCH
DESIGN AND METHODS: A total of 129 insulin-requiring adults who were employed
outside of the home were assessed on a single occasion. They completed two work
system measures (The Work Environment Scale and The Work Apgar Scale) and two
quality-of-life measures (The Diabetes Quality of Life Scale and The Appraisal of
Diabetes Scale). Subjects also participated in a semi-structured interview
concerning the interaction of work and diabetes. Glycemic control was assessed by
using HbAlc results. Demographic data (age, sex, diabetes type, duration of
diabetes, number of diabetes-related medical complications) were gathered from
the charts. RESULTS: Concerning glycemic control, neither of the work system
measures was a significant predictor of HbAlc. Concerning psychosocial
adaptation, supervisor support was found to be a significant predictor of
positive appraisal and diabetes-related satisfaction. Involvement and coworker
cohesion also predicted aspects of diabetes-related quality of life. Interview
themes showed that for a minority (18%), diabetes affected choice of work and
that for a majority (60%), diabetes affected relationships at work and raised
financial/job concerns (49%). Most adjust their diet, blood glucose testing, and
exercise regimen through work-related modifications. CONCLUSIONS: For insulin
treated adults with diabetes, work system variables do not directly relate to
glycemic control, but they do relate to psychosocial adaptation. Future work
should examine further the specific aspects of the workplace that might affect
adaptation, with the goal being to develop worksite interventions that target not
only the employee with diabetes but also their supervisors and coworkers.
PMID- 10189532
TI - Insulin sensitivity in subjects with type 2 diabetes. Relationship to
cardiovascular risk factors: the Insulin Resistance Atherosclerosis Study.
AB - OBJECTIVE: Among nondiabetic subjects, insulin resistance has been associated
with increased cardiovascular risk factors, including dyslipidemia, hypertension,
impaired fibrinolysis, and coagulation. Less is known about the relationship
between insulin resistance and cardiovascular risk factors in subjects with type
2 diabetes. RESEARCH DESIGN AND METHODS: To examine this issue, we determined
insulin sensitivity (SI) in 479 type 2 diabetic subjects by minimal model
analyses of frequently sampled intravenous glucose tolerance tests in the Insulin
Resistance Atherosclerosis Study (IRAS), a large multicenter study of insulin
sensitivity and cardiovascular disease in African-Americans, Hispanics, and non
Hispanic whites. We defined insulin-sensitive subjects as having SI > or = 1.61 x
10(-4) min-1.microU-1.ml-1 (above median in nondiabetic subjects of all ethnic
groups in the IRAS). Using this definition, only 37 type 2 diabetic subjects were
insulin sensitive, and the remaining 442 were insulin resistant. RESULTS: After
adjustment for age, sex, ethnicity, and clinic, insulin resistance was
significantly correlated with total triglycerides, VLDL cholesterol, VLDL
triglyceride, fibrinogen, PAI-1, and fasting glucose, and was inversely
correlated with HDL cholesterol level and LDL size. Carotid intimal-medial
thickness was greater in insulin-resistant than in insulin-sensitive subjects,
but this difference was not statistically significant. After further adjustment
for waist circumference (marker of visceral adiposity), insulin-resistant
subjects continued to have higher plasminogen activator inhibitor 1 and VLDL
triglyceride levels, lower HDL cholesterol levels, and smaller LDL particle size
than did insulin-sensitive subjects. After further adjustment for fasting glucose
levels, these results were very similar. CONCLUSIONS: We conclude that insulin
resistant type 2 diabetic subjects have more atherogenic cardiovascular risk
factor profiles than insulin-sensitive type 2 diabetic subjects and that this is
only partially related to increased obesity and an adverse body fat distribution.
PMID- 10189534
TI - Glycemic control in patients with diabetes in Finland.
AB - OBJECTIVE: To evaluate the quality of diabetes care at a national level in
Finland, using level of glycemia as a determinant of success in treatment.
RESEARCH DESIGN AND METHODS: Physicians and diabetes nurses in 76 randomly
selected clinics (59 primary care units and 17 hospitals) evenly covering the
whole of Finland were asked to fill in a questionnaire asking for data based on
the 1993 medical records of a random sample of 50 diabetic patients from each
center (total n = 3,800). HbAlc was used as an index of glycemic control.
RESULTS: Information on 3,195 (84%) diabetic patients was received. HbAlc was
measured in 67% of the patients in 1993. The mean HbAlc in the whole population
was 8.6 +/- 1.9% (normal range 4-6%). Some 25% of patients had HbAlc < or = 7.3%,
while 25% had HbAlc > or = 9.7%. The mean HbAlc was 8.8 +/- 1.9% in type 1 and
8.5 +/- 1.9% in type 2 diabetic patients. There was no sex difference in the
HbAlc level in type 1 diabetic patients. However, male type 2 diabetic patients
had better glycemic control than female patients (8.3 +/- 1.9 vs. 8.8 +/- 1.9%, P
< 0.0001). The sex difference was independent of the type of therapy. The mean
level of glycemic control was lowest among individuals with the shortest duration
of diabetes. After 7-9 years after the diagnosis, there was no change in the mean
level of glycemia. CONCLUSIONS: Average glycemic control is poor in a majority of
the diabetic patients in Finland. Better treatment strategies and methods should
be used to improve glycemic control and to reduce long-term complications.
PMID- 10189535
TI - Biopsychobehavioral model of risk of severe hypoglycemia. Self-management
behaviors.
AB - OBJECTIVE: To identify self-management antecedents of low blood glucose (BG) (<
3.9 mmol/l) that might be easily recognized, treated, or avoided altogether.
RESEARCH DESIGN AND METHODS: Ninety-three adults with type 1 diabetes (age, 35.8
+/- 8 years [mean +/- SD]; duration of diabetes, 17.0 +/- 11 years; daily insulin
dose, 0.58 +/- 0.18 U/kg; and HbAlc, 8.6 +/- 1.8%) were recruited to participate
in the study. Of the 93 subjects, 42 had a history of severe hypoglycemia (SH),
defined as two or more hypoglycemic episodes in the preceding 12 months, and 51
subjects had no history of SH (No-SH) in the same time period. Before each of 70
BG measurements obtained over a 3-week period, subjects used a handheld computer
to record whether their most recent insulin, food, and exercise was more than,
less than, or the same as usual. Associations among self-management behaviors
preceding BG readings < 3.9 mmol/l versus those preceding BG readings of 5.6-7.8
mmol/l were determined using chi 2 tests, analyses of variance, and logistic
regression analyses. RESULTS: Analysis of 6,425 self-management/self-monitoring
of BG events revealed that the usual amounts of insulin, food, and exercise
preceded the events 58.3% of the time. No significant differences were observed
for changes in insulin before readings of BG < 3.9 mmol/l versus 7.8 < BG > 5.6
mmol/l, but significantly less food (P < 0.01) was eaten and more exercise (P <
0.001) was performed before the low BG measurement. No interactions between SH
and No-SH groups and management behaviors were observed. However, each of the
three management variables entered significantly in a logistic model that
predicted 61% of all readings of BG < 3.9 mmol/l. CONCLUSIONS: Subjects with a
history of SH did not report managing their diabetes differently from those with
no such history. Specifically, when low BG occurred, the preceding management
behaviors, although predictive of low BG, were not different in SH and No-SH
subjects. Overall, self-management behaviors did not distinguish SH from No-SH
subjects. Thus, even though it might be beneficial for all patients to review
their food and exercise management decisions to reduce their frequency of low BG,
an educational intervention whose content stresses insulin, food, and exercise
would be unlikely by itself to be sufficient to reduce the frequency of SH.
PMID- 10189536
TI - Cotherapy with recombinant human insulin-like growth factor I and insulin
improves glycemic control in type 1 diabetes. RhIGF-I in IDDM Study Group.
AB - OBJECTIVE: To study the effects of 12 weeks of cotherapy with recombinant human
IGF-I (rhIGF-I) and insulin on glycemic control in patients with type 1 diabetes.
RESEARCH DESIGN AND METHODS: The study population consisted of 223 patients who
ranged in age from 11-66 years and were randomized in a double-blind study to
receive 12 weeks of treatment with twice-daily subcutaneous injections of placebo
(n = 54), or rhIGF-I at a dose (A.M/P.M) of 40/40 micrograms/kg (n = 56), 80/40
micrograms/kg (n = 57), or 80/60 micrograms/kg (n = 56), while continuing to
receive standard insulin therapy. Patients were instructed to test blood glucose
levels four times daily and adjust insulin doses to optimize blood glucose
control. HbAlc, insulin requirements, body weight, and parameters of the IGF-IGF
binding protein axis were assessed before and during treatment. RESULTS: All
groups were comparable at baseline with respect to mean age, gender distribution,
duration of diabetes, HbAlc, and BMI. Cotherapy with rhIGF-I/insulin produced a
mean decrease in HbAlc of 1.2%, compared with a 0.7% decrease in HbAlc for
patients receiving intensified insulin therapy alone (P < or = 0.01). Subjects
receiving rhIGF-I/insulin cotherapy also decreased their daily insulin usage by
11-19%, compared with a 7% increase in insulin usage reported by the placebo
group. Moreover, the incidence of hypoglycemia was similar in subjects treated
with rhIGF-I/Insulin cotherapy compared with those treated with insulin alone,
despite the better glycemic control of the former group. The 40/40 dose of rhIGF
I was well tolerated. Higher doses of rhIGF-I did not further improve efficacy
yet were associated with unacceptable levels of adverse events, including edema,
jaw pain, and early worsening of retinopathy. CONCLUSIONS: These results
demonstrate that rhIGF/insulin cotherapy improves glycemic control in patients
with type 1 diabetes better than optimized insulin management alone; longer-term
trials would be required to determine an acceptable benefit-risk profile.
PMID- 10189537
TI - Detection of autonomic sympathetic dysfunction in diabetic patients. A study
using laser Doppler imaging.
AB - OBJECTIVE: To study signs of the disturbed reflex autonomic sympathetic nerve
function in type 1 and type 2 diabetic patients. RESEARCH DESIGN AND METHODS:
Measurements were made on 15 type 1 (duration 13-32 years) and on 50 recently
diagnosed type 2 diabetic patients (duration 3-4 years). The vasoconstrictor
responses in the distal phalanx of the middle finger (locally heated to 40
degrees C) to the cooling of the contralateral arm were measured using Laser
Doppler Imaging (LDI). A vasoconstriction index (VAC) was calculated taking age
into account and was compared with reference values obtained in 80 control
subjects. The diabetic patients were also studied with deep-breathing tests
(i.e., the heart-rate variation expressed as the expiration-to-inspiration [E/I]
ratio, a test of parasympathetic nerve function). RESULTS: The vasoconstrictor
responses to indirect cooling (VAC) were significantly reduced in the fingers of
the diabetic patients, both type 2 (0.77 +/- 0.02 V; P < 0.01) and type 1 (0.83
+/- 0.04 V; P < 0.001), compared with the healthy control subjects (0.65 +/-
0.01); the age-corrected VAC (VACz) was slightly more impaired in type 1 than in
type 2 diabetic patients. The frequency of an abnormal VACz corresponded well to
the frequency of an abnormal E/I ratio in type 1 diabetic patients (approximately
50%), whereas the frequency of an abnormal VACz was significantly higher than an
abnormal E/I ratio among type 2 diabetic patients (11/50 vs. 4/50; P < 0.05).
CONCLUSIONS: Both type 1 and type 2 diabetic patients have impaired cutaneous
blood flow regulation. The VAC index seems to be a promising tool for detection
of subclinical changes in autonomic sympathetic function.
PMID- 10189538
TI - Possible sources of discrepancies in the use of the Semmes-Weinstein
monofilament. Impact on prevalence of insensate foot and workload requirements.
AB - OBJECTIVE: The purpose of this study was to evaluate the effects of different
testing sites and buckling strengths on the sensitivity and specificity of using
the Semmes-Weinstein monofilament to detect patients with insensate foot. The
impact on workload required to educate and follow up these high-risk individuals
was estimated by modeling in our patient population with a documented status of
neuropathy. RESEARCH DESIGN AND METHODS: Using the 5.07/10-g monofilament, one
observer tested 132 randomly selected subjects with diabetes at five sites on the
right foot. The sensitivity and specificity of each site and combinations of
sites in detecting vibration perception threshold > 40 was calculated. In
addition, two monofilaments, one with a buckling force of 5 g and the other with
a force of 15 g, were compared by testing 200 randomly selected patients. An
estimate of the prevalence of insensate foot and workload was made by modeling
the findings to the 5,270 patients with neuropathy status registered on our
computerized database. RESULTS: Specificity of the 5.07/10-g monofilament to
detect insensate foot at each of the five sites is high, at approximately 90%,
but there is considerably more variation and lower sensitivity, ranging from 44
71%. Data derived from the use of different combinations of sites showed that
more stringent criteria are associated with lower sensitivity but higher
specificity. If the foot is considered insensate when either of sites 3 and 4
(plantar aspect of the first and fifth metatarsal heads, respectively) cannot
feel the monofilament, there is reasonable sensitivity and specificity (80-86%,
respectively). By modeling on our diabetes center population, it can be
demonstrated that the choice of different methodologies leads to different
conclusions about the prevalence of severe neuropathy, ranging from 3.4 to 29.3%.
CONCLUSIONS: Using a combination of sites 3 and 4 for monofilament testing gives
a reasonable compromise for time, sensitivity, and specificity. Minor changes in
sensitivity and specificity can lead to major changes in the prevalence of
neuropathy, with implications for workload.
PMID- 10189539
TI - Effectiveness of human ultralente versus NPH insulin in providing basal insulin
replacement for an insulin lispro multiple daily injection regimen. A double
blind randomized prospective trial. The Canadian Lispro Study Group.
AB - OBJECTIVE: To compare human ultralente (UL) insulin with human NPH insulin as
basal insulin replacement in patients who use insulin lispro before meals.
RESEARCH DESIGN AND METHODS: There were 178 patients with type 1 diabetes who
were randomized to receive either human NPH or UL insulin once daily at bedtime
in a 1-year double-blind clinical study. Eight-point blood glucose profiles were
collected once monthly in the first 4 months, then every 2 months for the
remainder of the study. Patients were also asked to perform premeal blood glucose
measurements every day throughout the study. If before-supper blood glucose
levels consistently exceeded 8 mmol/l despite optimal postprandial control with
the lunch dose of insulin lispro, a second dose of basal insulin before breakfast
was administered. RESULTS: For the group as a whole, insulin doses before meals
and basal insulin doses were similar at baseline. At study's end, meal doses
remained the same (30 +/- 1 U/day for UL., 29 +/- 1 U/day for NPH), while basal
requirements were somewhat higher for the UL group than the NPH group: 30 +/- 1
U/day vs. 26 +/- 1 U/day, respectively (P < 0.05). The rates of severe
hypoglycemia were similar for patients on NPH (0.05 +/- 0.03 per patient every 30
days) and for UL (0.07 +/- 0.04 per patient every 30 days) insulin. There was no
significant difference for glycemic control between the NPH and UL groups overall
(HbAlc at the end of the study: 7.6 +/- 0.1 vs. 7.7 +/- 0.1%, respectively), and
by study's end a similar number of patients in the NPH and the UL groups needed
to be switched to twice daily basal insulin (21 and 24%, respectively). Patients
requiring twice-daily injections of basal insulin had a longer duration of
diabetes (17.8 +/- 1.5 vs. 14.0 +/- 0.8 years, P < 0.05) and a highest baseline
HbAlc (8.6 +/- 0.1 vs. 8.0 +/- 0.1%, P < 0.002) and were significantly older (38
+/- 2 vs. 34 +/- 1 years, P < 0.007). Patients who were switched to twice-daily
NPH insulin had lower HbAlc levels at study's end compared with those switched to
twice-daily UL insulin (7.7 +/- 0.2 vs. 8.2 +/- 0.3%), but this difference was
not statistically significant. Distribution of hypoglycemia across the day was
also similar in both groups. CONCLUSIONS: UL or NPH insulin, when used as the
basal insulin for multiple injection regimens, results in similar glycemic
control in patients using insulin lispro before meals. However, in patients who
require a second injection of basal insulin, NPH insulin appears to provide lower
prebreakfast and prelunch glucose levels compared with UL insulin.
PMID- 10189540
TI - Intact proinsulin and beta-cell function in lean and obese subjects with and
without type 2 diabetes.
AB - OBJECTIVE: Type 2 diabetes is a heterogeneous disease in which both beta-cell
dysfunction and insulin resistance are pathogenetic factors. Disproportionate
hyperproinsulinemia (elevated proinsulin/insulin) is another abnormality in type
2 diabetes whose mechanism is unknown. Increased demand due to obesity and/or
insulin resistance may result in secretion of immature beta-cell granules with a
higher content of intact proinsulin. RESEARCH DESIGN AND METHODS: We investigated
the impact of obesity on beta-cell secretion in normal subjects and in type 2
diabetic patients by measuring intact proinsulin, total proinsulin
immunoreactivity (PIM), intact insulin, and C-peptide (by radioimmunoassay) by
specific enzyme-linked immunosorbent assays in the fasting state and during a 120
min glucagon (1 mg i.v.) stimulation test. Lean (BMI 23.5 +/- 0.3 kg/m2) (LD) and
obese (30.1 +/- 0.4 kg/m2) (OD) type 2 diabetic patients matched for fasting
glucose (10.2 +/- 0.6 vs. 10.3 +/- 0.4 mmol/l) were compared with age- and BMI
matched lean (22.4 +/- 0.6 kg/m2) (LC) and obese (30.8 +/- 0.9 kg/m2) (OC) normal
control subjects. RESULTS: Diabetic patients (LD vs. LC and OD vs. OC) had
elevated fasting levels of intact proinsulin 6.6 +/- 1.0 vs. 1.6 +/- 0.3 pmol/l
and 7.7 +/- 2.0 vs. 1.2 +/- 0.2 pmol/l; PIM: 19.9 +/- 2.5 vs. 5.4 +/- 1.0 pmol/l
and 29.6 +/- 6.1 vs. 6.1 +/- 0.9 pmol/l; and total PIM/intact insulin: 39 +/- 4
vs. 15 +/- 2% and 35 +/- 5 vs. 13 +/- 2%, all P < 0.01. After glucagon
stimulation, PIM levels were disproportionately elevated (PIM/intact insulin
based on area under the curve analysis) in diabetic patients (LD vs. LC and OD
vs. OC): 32.6 +/- 6.7 vs. 9.2 +/- 1.1% and 22.7 +/- 5.2 vs. 9.1 +/- 1.1%, both P
< 0.05. Intact insulin and C-peptide net responses were significantly reduced in
type 2 diabetic patients, most pronounced in the lean group. The ratio of intact
proinsulin to PIM was higher in diabetic patients after stimulation in both LD
versus LC: 32 +/- 3 vs. 23 +/- 2%, and OD versus OC: 28 +/- 4 vs. 16 +/- 2%, both
P < 0.01. In obese normal subjects, intact proinsulin/PIM was lower both in the
fasting state and after glucagon stimulation: OC versus LC: 22 +/- 3 vs. 33 +/-
3% (fasting) and 16 +/- 2 vs. 23 +/- 2% (stimulated), both P < 0.05. CONCLUSIONS:
Increased secretory demand from obesity-associated insulin resistance cannot
explain elevated intact proinsulin and disproportionate hyperproinsulinemia in
type 2 diabetes. This abnormality may be an integrated part of pancreatic beta
cell dysfunction in this disease.
PMID- 10189541
TI - T-cell insulitis found in anti-GAD65+ diabetes with residual beta-cell function.
A case report.
AB - CASE HISTORY: We recently encountered a 65-year-old anti-GAD+ diabetic woman with
residual beta-cell function who was proved to have T-cell insulitis. The
proportion of CD4+ and CD8+ cells varied among individual islets, although CD4+
cells tended to be the predominant T-cell type in the islets examined. All of the
islets examined still contained insulin, suggesting that beta-cell mass may have
been preserved. DISCUSSION: It is well known that lymphocytic infiltration of
pancreatic islets, a condition referred to as "insulitis," is seen in acute-onset
type 1 diabetes at autopsy and in biopsy specimens. However, there have been no
proven cases of insulitis in type 1 diabetes with residual beta-cell function. We
believe that this is the first type 1 diabetic patient with residual beta-cell
function who was proven to have T-cell insulitis. This novel evidence will
contribute to the proper classification and treatment of diabetes and to a better
understanding of the pathophysiology of type 1 diabetes.
PMID- 10189542
TI - Relationship between glomerular hyperfiltration and ACE insertion/deletion
polymorphism in type 1 diabetic children and adolescents.
AB - OBJECTIVE: Glomerular hyperfiltration may predict diabetic nephropathy in type 1
diabetes, and some studies suggest that the ACE D allele is associated with
diabetic nephropathy. The aim of this study was to examine a possible
relationship between glomerular hyperfiltration and ACE insertion/deletion (I/D)
polymorphism in type 1 diabetic children and adolescents. RESEARCH DESIGN AND
METHODS: A cross-sectional study was conducted to examine the relationship
between glomerular hyperfiltration and ACE (I/D) polymorphism in 76 type 1
diabetic children and adolescents without diabetic nephropathy (mean +/- SD: age
16 +/- 3 years; diabetes duration 7 +/- 4 years; age at diabetes onset 9 +/- 4
years; HbA1c 9.5 +/- 1.9%). Glomerular hyperfiltration (defined as a glomerular
filtration rate [GFR] > or = 135 ml.min-1. 1.73 m-2 and by 51Cr-labeled EDTA
plasma disappearance technique) and ACE I/D genotypes and plasma levels (enzyme
linked immunosorbent assay [ELISA] method) were determined. RESULTS: Of the
patients, 29 (38%) displayed glomerular hyperfiltration. An association between
glomerular hyperfiltration and ACE (I/D) polymorphism was observed (chi 2 = 7.09,
P = 0.029) because of a reduced proportion of DD genotypes among patients with
glomerular hyperfiltration (4 vs. 19; chi 2 = 6.03, P = 0.014) and not because of
an excess of the II genotype (5 vs. 9; chi 2 = 0.04, P = 0.83). Age, diabetes
duration, age at diabetes onset, and HbA1c were not different according to
genotype. Patients with glomerular hyperfiltration had low plasma ACE levels,
compared with those with normal glomerular filtration (457 +/- 157 vs. 553 +/-
186 micrograms/l; P = 0.027). CONCLUSIONS: These results suggest an unexpected
association between glomerular hyperfiltration and ACE (I/D) polymorphism,
characterized by a defect of the DD genotype among type 1 diabetic children and
adolescents with glomerular hyperfiltration.
PMID- 10189544
TI - Beyond "compliance" is "adherence". Improving the prospect of diabetes care.
AB - The purpose of this study is to evaluate existing research in the area of patient
"compliance," to endorse reconceptualizing "compliance" in terms of "adherence,"
and to discuss the benefits of such a change for medical practitioners. This
study critically reviews existing medical, nursing, and social scientific
research in the area of patient "compliance." We assert that the literature
reviewed is flawed in its focus on patient behavior as the source of
"noncompliance," and neglects the roles that practitioners, the American medical
system, and patient-practitioner interaction play in medical definitions of
"compliance." The term "compliance" suggests a restricted medical-centered model
of behavior, while the alternative "adherence" implies that patients have more
autonomy in defining and following their medical treatments. We suggest that
while the change in terminology is minor, it reflects an important paradigmatic
shift for thinking about the delivery of health care. By enabling practitioners
to more accurately identify patients' social and economic constraints and to
provide them with more efficient educational and financial resources, this type
of change will improve patient care. In general, by moving to a more social
paradigm for understanding patient behavior, practitioners can expand the types
of explanations, and therefore the types of solutions, they have for therapeutic
adherence.
PMID- 10189545
TI - American Diabetes Association Annual Meeting, 1998. Nephropathy and retinopathy.
PMID- 10189543
TI - The Diabetes Prevention Program. Design and methods for a clinical trial in the
prevention of type 2 diabetes.
AB - The Diabetes Prevention Program is a randomized clinical trial testing strategies
to prevent or delay the development of type 2 diabetes in high-risk individuals
with elevated fasting plasma glucose concentrations and impaired glucose
tolerance. The 27 clinical centers in the U.S. are recruiting at least 3,000
participants of both sexes, approximately 50% of whom are minority patients and
20% of whom are > or = 65 years old, to be assigned at random to one of three
intervention groups: an intensive lifestyle intervention focusing on a healthy
diet and exercise and two masked medication treatment groups--metformin or
placebo--combined with standard diet and exercise recommendations. Participants
are being recruited during a 2 2/3-year period, and all will be followed for an
additional 3 1/3 to 5 years after the close of recruitment to a common closing
date in 2002. The primary outcome is the development of diabetes, diagnosed by
fasting or post-challenge plasma glucose concentrations meeting the 1997 American
Diabetes Association criteria. The 3,000 participants will provide 90% power to
detect a 33% reduction in an expected diabetes incidence rate of at least 6.5%
per year in the placebo group. Secondary outcomes include cardiovascular disease
and its risk factors; changes in glycemia, beta-cell function, insulin
sensitivity, obesity, diet, physical activity, and health-related quality of
life; and occurrence of adverse events. A fourth treatment group--troglitazone
combined with standard diet and exercise recommendations--was included initially
but discontinued because of the liver toxicity of the drug. This randomized
clinical trial will test the possibility of preventing or delaying the onset of
type 2 diabetes in individuals at high risk.
PMID- 10189546
TI - Marked weight loss in a type 2 diabetic patient treated with acarbose.
PMID- 10189547
TI - RAGE Gly82Ser polymorphism in diabetic microangiopathy.
PMID- 10189548
TI - Blunted erythropoietin response to anemia in type 1 diabetic patients.
PMID- 10189549
TI - Primary angioplasty compared with thrombolysis in acute myocardial infarction in
diabetic patients.
PMID- 10189550
TI - Underdiagnosis of type 2 diabetes by use of American Diabetes Association
criteria.
PMID- 10189551
TI - Burden of diabetes in Malta, 1996-2020.
PMID- 10189552
TI - Significant improvement in HbA1c in a morbidly obese type 2 diabetic patient
after gastric bypass surgery despite relatively small weight loss.
PMID- 10189553
TI - Concordance between American Diabetes Association and World Health Organization
criteria in a northwestern Italian population.
PMID- 10189554
TI - Screening for gestational diabetes.
PMID- 10189555
TI - Natural history of macrovascular disease in type 2 diabetes. Role of insulin
resistance.
PMID- 10189556
TI - Risk factors for macrovascular disease in type 2 diabetes. Classic lipid
abnormalities.
PMID- 10189557
TI - Dyslipidemia of central obesity and insulin resistance.
PMID- 10189558
TI - Diabetes and cardiovascular disease.
PMID- 10189559
TI - Abnormalities of coagulation and fibrinolysis in insulin resistance. Evidence for
a common antecedent?
AB - Insulin resistance is associated not only with the classic cardiovascular risk
factors of hypertension and dyslipidemia, but also with several disorders of
coagulation and fibrinolysis. Elevated concentrations of the fibrinolytic
inhibitor plasminogen activator inhibitor-1 are associated with insulin
resistance. In experimental systems, increased expression and secretion of
plasminogen activator inhibitor-1 by hepatocyte and endothelial cell lines can be
induced by insulin, proinsulin-like molecules, triglyceride-rich lipoproteins and
oxidized LDL, as well as by inducing insulin resistance in isolated hepatocytes.
Concentrations of the endothelial cell protein von Willebrand factor are elevated
in insulin-resistant states, suggesting that abnormalities of capillary
endothelium, as well as those reported for endothelium-dependent vasodilatation,
may play a role in the etiology of insulin resistance. Levels of a third
coagulation factor, fibrinogen, are elevated in insulin-resistant subjects, an
association that suggests a possible role for acute-phase cytokines in the
abnormalities of coagulation and endothelial function. It is proposed that the
recent observations of secretion of interleukin-6 by adipose tissue, combined
with the actions of adipose tissue-expressed tumor necrosis factor-alpha in
obesity-induced insulin resistance, could underlie the associations of insulin
resistance with endothelial dysfunction, coagulopathy, and coronary heart
disease.
PMID- 10189560
TI - Theoretical mechanisms by which hyperglycemia and insulin resistance could cause
cardiovascular diseases in diabetes.
PMID- 10189561
TI - Effects of oral antihyperglycemic agents in modifying macrovascular risk factors
in type 2 diabetes.
AB - Management of patients with type 2 diabetes should focus on decreasing the excess
macrovascular disease with which it is associated as well as preventing or
minimizing microvascular disease. Near-normoglycemic control can reduce
microvascular disease. Reducing macrovascular disease requires concomitant
management of the cardiovascular risk factors (components of the insulin
resistance syndrome) associated with type 2 diabetes. The first phase of such
treatment is to identify the effects that the various drugs to treat the
hyperglycemia are likely to have on these associated cardiovascular risk factors.
Appropriate combinations of antihyperglycemic agents should be selected for
specific patients to help achieve good glycemic control and produce beneficial,
or at least nondetrimental, effects on cardiovascular risk.
PMID- 10189562
TI - Effect of insulin therapy on macrovascular risk factors in type 2 diabetes.
AB - Many patients with type 2 diabetes require insulin therapy for improved glycemic
control after beta-cell failure. However, many physicians are reluctant to
institute insulin therapy in type 2 diabetes for fear of accelerating
atherosclerosis. The epidemiological evidence is reasonably sound that
hyperinsulinism correlates with increased cardiovascular disease in nondiabetic
people and those with early type 2 diabetes. It is much less clear, however, that
insulin concentration plays a negative role when less well controlled diabetes is
considered. The data are more consistent, in fact, with the glucose hypothesis,
i.e., that hyperglycemia is a risk factor, although the magnitude of the glucose
effect is not well defined. Certainly, the dysmetabolism associated with poor
glycemic control could increase the risk of macrovascular events through well
known mechanisms. There is direct evidence that insulin therapy can reduce the
risk of macrovascular events by improving glycemic control and diabetes
associated dyslipidemias, although the beneficial effects may be significantly
compromised by excessive weight gain. Insulin therapy does not appear to induce
hypertension independent of changes in body weight. It is concluded that optimal
glycemic control confers a known benefit and can only be achieved with insulin
therapy in some people with type 2 diabetes. In these circumstances, the use of
insulin has a net benefit on cardiovascular risk, mediated primarily through
improvement in dyslipidemia and glycemia itself.
PMID- 10189563
TI - Epidemiological studies on the effects of hyperglycemia and improvement of
glycemic control on macrovascular events in type 2 diabetes.
AB - The relation of glycemia to coronary heart disease in subjects with type 2
diabetes is controversial. Recent data have suggested a significant relation of
glycemia to cardiovascular disease in both type 2 diabetes and in subjects with
impaired glucose tolerance, although the relation of glycemia to cardiovascular
disease appears to be weaker than the relation of glycemia to microvascular
disease.
PMID- 10189564
TI - Oral agent therapy in the treatment of type 2 diabetes.
PMID- 10189565
TI - Overview of current therapeutic options in type 2 diabetes. Rationale for
combining oral agents with insulin therapy.
PMID- 10189566
TI - Rationale for the use of insulin therapy alone as the pharmacological treatment
of type 2 diabetes.
AB - Before any treatment of type 2 diabetes in accordance with the principles of
evidence-based medicine can be generally recommended, the considerable disease
heterogeneity must be taken into account, and randomized controlled intervention
trials directed to cardiovascular and microangiopathic organ damage end points
must be performed for the various subgroups of patients. Until then, it appears
prudent to treat the typical Caucasian type 2 diabetic patient primarily by
nondrug therapies, and if they fail to achieve the patient's individual treatment
goals, then insulin treatment should be initiated. Treatment of type 2 diabetic
patients with insulin alone, aimed at the patient's individual therapeutic goals,
is effective and safe when conducted as an integral part of specific and
structured treatment and teaching programs. Insulin treatment can be safely used
to achieve near-normal HbA1c levels (< 7.0-7.5%) if prevention of diabetic
microangiopathy is indicated, or to maintain HbA1c levels < 8.5-9.0% if catabolic
symptoms due to insulin deficiency are to be prevented.
PMID- 10189567
TI - Biomarkers in environmental health research & practice.
PMID- 10189568
TI - DOE emergency planning & emergency management using emergency response planning
guidelines (ERPGS) and temporary emergency exposure levels (TEELs).
AB - Facilities within the Department of Energy community perform emergency management
to conform with Federal regulations, internal guidance and good management
practice. Emergency management in this context includes hazard analysis,
consequence assessment, and development of emergency plans including protective
actions for workers, uninvolved workers, and the general public. ERPGs are used
as the action level for decision making with regards to accidental chemical
releases; AEGLs are also being developed for that purpose. DOE actively
participates in the development of ERPGs and AEGLs, however, there is a time gap
inherent in the development of community exposure limits (which can be months or
years) and the need for community exposure limits (which must be implemented
now). In recognition of this problem, the DOE Subcommittee on Consequence
Assessment and Protective Actions (SCAPA) has developed a hierarchy of alternate
exposure limits (Temporary Emergency Exposure Limits, TEELs) to use as temporary
guidance for emergency planning for those chemicals for which an ERPG or an AEGL
does not exist. This presentation will discuss DOE's involvement in development
of ERPGs and AEGLs, including their application, and will discuss the development
and use of TEELs (including advantages and disadvantages).
PMID- 10189569
TI - Applications of an acute assessment methodology used for combustion facilities.
AB - Two approaches for evaluating potential health impact from short-term (1 hour)
inhalation exposure to air emissions from combustion facilities are presented.
This information was included as part of the health risk assessment (HRA)
conducted for each proposed facility in conjunction with regulatory requirements
for obtaining an operating permit. Since the facilities being evaluated have
either not yet been constructed or are not yet operational, air concentrations
(particulate and vapor) must first be estimated using data from similar and
operational facilities. A chemical's modeled air concentration was then compared
to its acute toxicity value (ATV) selected from established Occupational Exposure
Limits (OEL) or acute toxicity databases, if available. Analogous to the current
USEPA approach for estimating noncancer health effects, acute hazard quotients
(AHQs) were summed and compared to a level of one. When the summation of the AHQs
exceeded unity, the chemicals were separated by target organ and health effects
based on acute exposures. The author recognizes that the use of OELs has its
limitations. However, due to the lack of acute toxicity data and the advantage of
the completeness of the databases for OELs, this approach may be the best way to
evaluate for acute health concerns for the more than 70 compounds that may be
emitted from these facilities.
PMID- 10189570
TI - Breathing zone particle size and lead concentration from sanding operations to
remove lead based paints.
AB - The relationship between lead concentration in the dry film of lead based paints
applied to steel bulkheads aboard ship, the lead concentration found in the air
when the paint is removed by mechanical means, and blood lead concentrations of
workers involved in lead based paint removal has not been well characterized.
Intuitively a direct relationship must exist but confounding factors confuse the
issue. Simultaneous sampling procedures from the same paint removal operation may
differ by several orders of magnitude. The process from dried film to aerosol
(airborne dust) exposure, and on to dose can be separated into two major phases;
(1) generation of the dust and its transport through the air to the worker and
(2) uptake and dose related factors within the body. Both phases involve complex
interactions and there are a number of factors within each phase that
significantly affect the potential lead dose for the worker. This study attempts
to clarify the mechanisms involved in the generation and transportation of the
dust to the worker by evaluating the relationship of a number of key factors on
particle size and lead distribution within the aerosol dust generated when lead
based paint is removed by sanding. The study examined the relationship between
particle size in the dust and grit size of the abrasive. It also examined the
distribution of lead within selected particle sizes. The Mass Median Aerodynamic
Diameter (MMAD) was used as an indicator of change in the particle size
distribution. Particle size distributions were evaluated using a TSI Aerodynamic
Particle Sizer, a five stage cyclone and scanning electron microscopy. Lead
distribution was determined using the five stage cyclone, and personal or area
samples analyzed using inductively coupled plasma (ICP). Mass concentrations were
evaluated using a MIE Mass Concentration Analyzer and gravimetric analysis of
filter samples collected in the breathing zone. Student's t-tests were used to
evaluate changes in MMADs, mass concentrations and other indices for inter and
intra-grit size samples. Correlation coefficients (Pearson's r) were used to
determine the relationship between factors. Findings of the research indicated
that the particle size distribution in the dust is directly related to the grit
size of the abrasive (i.e. inversely related to the abrasive grit number).
Particulate mass concentrations of dust varied directly with abrasive grit
number. The distribution of lead did not appear to be affected by grit size of
the abrasive in that the lead distribution within the particle size ranges
remained homogeneous and consistent with the lead concentration in the dried
film. Mass concentrations of lead in air samples varied directly with lead
concentration in the bulk coating. Results of this project, coordinated with
deposition modeling and bioavailability studies will be useful in the development
of a model to characterize lead dose to workers based on known parameters within
the work specifications.
PMID- 10189571
TI - Chemical detection in deployment toxicology using high speed gas chromatography
with a solvating mobile phase and time-of-flight mass spectrometry.
AB - Solvating gas chromatography (SGC) involves a mobile phase that is a
supercritical fluid at the column inlet (typically 100-350 atm) and a gas upon
exiting the column at ambient pressure. SGC has characteristics of both
supercritical fluid chromatography and gas chromatography, and may be adaptable
to a system with characteristics approaching a "universal chromatograph" capable
of analyzing many classes of compounds on one instrument. We have recently found
that using a solvating mobile phase such as CO2, together with small, spherical
particle-packed capillary columns can offer significant advantages for rapid
chemical analysis. A need exists in operational military settings to rapidly
detect a wide range of chemicals with potential adverse health effects for
exposed personnel. A separation step improves analytical capability by reducing
or eliminating chemical background for better detection limits, and purifies or
isolates target analytes and unknowns for improved identification. SGC, coupled
to a high volume vapor/aerosol sampler and a rapid mass spectrometric detector
such as a time-of-flight mass spectrometer could provide rapid, positive
identification of separated compounds, with the resulting chromatographic and
mass spectral data stored in digital format for future retrieval. Such a system
will significantly advance the ability of military commanders to detect airborne
chemical agents rapidly and accurately, protecting the health of military
personnel.
PMID- 10189572
TI - Aerosol deposition modeling using ACSL.
AB - An aerosol deposition model has been written for inclusion into physiologically
based pharmacokinetic (PBPK) models, allowing PBPK model based risk assessments
to be performed for aerosolized materials. Previously, PBPK models could only
treat inhaled gases and vapors. The deposition model employs a semi-empirical
equation to describe extrathoracic deposition and employs data concerning the
geometry of the thoracic conducting airways as well as that of the gas exchange
regions of the lung to compute the deposited aerosol mass based on aerosol
diffusion, sedimentation, and impaction. Provisions are made to allow
calculations for polydisperse aerosols whose size distribution and mass vary with
time. Variations in the model subject's respiration can be accommodated through
selection of respiratory parameters at model startup as well as through
consideration of carbon dioxide stimulation of respiration. The model is compared
with other similar calculations and experimental data to validate the
calculations. An example model application is presented in the form of a
comparison of two inhalation atmospheres, one from an inhalation toxicity study
and one from a similar atmosphere produced for fire extinguishing agent testing.
PMID- 10189573
TI - Acute lung injury, acute respiratory distress syndrome and inhalation injury: an
overview.
AB - Acute Lung Injury (ALI) and the Acute Respiratory Distress Syndrome (ARDS) are
severe respiratory diseases that have a very poor prognosis and have numerous
causes. Despite a great deal of research and investigation since the initial
description of ARDS 30 years ago many questions about the pathogenesis, treatment
and outcome of the disease remain unanswered. Although there is evidence to
suggest that outcome of ALI and ARDS is improving, the reasons why are unknown
and there is not yet a well developed treatment for these diseases. Inhalation
injury resulting from exposure to pyrolysis and combustion atmospheres is among
the causes of ALI/ARDS. Little is known of the mechanisms of fire related
inhalation injury that results in the development of ALI/ARDS. There is a paucity
of information about fire atmosphere exposure response relationships for smoke
induced inhalation injury. Although there is considerable information about the
pulmonary toxicity of many of the more common constituents of fire atmospheres,
little is known about the pulmonary toxicity of mixtures of these constituents.
Fire related pulmonary health risks are of particular concern to the Navy due to
the limited opportunity to escape the inhalation hazards posed by shipboard
fires. Consequently the Naval Medical Research Institute Detachment (Toxicology)
has undertaken a research program to develop research models of combustion
atmosphere induced ALI/ARDS which can be exploited to systematically address some
of the questions surrounding fire related ALI/ARDS. ALI/ARDS has been the topic
of a vast amount of research, numerous symposia, working groups and their
published proceedings, book chapters, and books. Less information is available
regarding experimental models of smoke induced lung damage, however the
literature on the subject is extensive. Consequently this article is intended to
provide the reader with a primer or cursory "overview" of ALI and ARDS from a
toxicological perspective and should not be considered comprehensive.
PMID- 10189574
TI - Mercury. Top of the hit parade for eight years.
AB - The Agency for Toxic Substances and Disease Registry (ATSDR) is the lead agency
within the U.S. Department of Health and Human Services (HHS) for providing
support to the federal response to releases of hazardous substances in the
environment. Since the Comprehensive Environmental Response Compensation and
Liability Act was passed and amended, ATSDR has represented HHS on the National
Response Team (NRT). The NRT role, and the subsequently established National
Response System, are described in the National Contingency Plan for Oil and
Hazardous Substances Releases (Title 40 Code of Federal Regulations, Section
300). As part of the National Response System, ATSDR can be called when a
hazardous substance is released. Consistently, one of the most common substances
ATSDR is called about is mercury, usually elemental mercury. This presentation
will provide some background statistics on these calls and some general response
options. Several specific cases that have occurred in the last few years will be
reviewed. These reviews will deal less with remedial options than with describing
common issues that arose, issues unique to the specific case, and the impact of
that case on the community. A brief discussion of risk communication issues and
ATSDR's response to those issues concludes the presentation.
PMID- 10189575
TI - Refining and blending of aviation turbine fuels.
AB - Aviation turbine fuels (jet fuels) are similar to other petroleum products that
have a boiling range of approximately 300F to 550F. Kerosene and No.1 grades of
fuel oil, diesel fuel, and gas turbine oil share many similar physical and
chemical properties with jet fuel. The similarity among these products should
allow toxicology data on one material to be extrapolated to the others.
Refineries in the USA manufacture jet fuel to meet industry standard
specifications. Civilian aircraft primarily use Jet A or Jet A-1 fuel as defined
by ASTM D 1655. Military aircraft use JP-5 or JP-8 fuel as defined by MIL-T-5624R
or MIL-T-83133D respectively. The freezing point and flash point are the
principle differences between the finished fuels. Common refinery processes that
produce jet fuel include distillation, caustic treatment, hydrotreating, and
hydrocracking. Each of these refining processes may be the final step to produce
jet fuel. Sometimes blending of two or more of these refinery process streams are
needed to produce jet fuel that meets the desired specifications. Chemical
additives allowed for use in jet fuel are also defined in the product
specifications. In many cases, the customer rather than the refinery will put
additives into the fuel to meet their specific storage or flight condition
requirements.
PMID- 10189576
TI - Toxicity of middle distillates from dermal exposure.
AB - This report focuses on recent studies that investigated the effects of kerosine
dermal exposure on neurotoxicity and reproductive/developmental toxicity.
Background toxicity information will also be reviewed for kerosine range mid
distillates. The kerosine range mid distillates have a carbon range of C9-C16 and
have a boiling range of 302-554 degrees F (150-290 degrees C). This category
includes kerosine, aviation fuels (e.g., Jet A, JP-5 and JP-8), no. 1 fuel oil
and diesel fuel oil. In general, the kerosine range mid distillates demonstrate
relatively low acute toxicity by any route of exposure. High inhalation exposures
can induce central nervous system depression characterized by ataxia,
hypoactivity and prostration. Kerosines are known to cause skin irritation and
inflammation under conditions of acute and repeated exposure in animals and
humans, but are only slightly irritating to the eye and are not skin sensitizers.
In addition, the absorption of kerosine range mid distillates through the skin
has been demonstrated to be fairly rapid, but limited to approximately 10-15% of
the applied dose after 24 hours. The kerosine range mid distillates are generally
inactive in genetic toxicity tests although positive studies have been reported.
Positive results, while at times equivocal, have been reported for straight run
kerosine and jet fuel A in the mouse lymphoma assay with metabolic activation,
and hydrodesulfurized kerosine (mouse) and jet fuel A (rat) in the bone marrow
cytogenetic assay. Effects on the nervous and reproductive systems have been
reported in humans and experimental animals under conditions where inhalation and
dermal exposure to specific kerosine type fuels are sometimes difficult to
separate. Recent laboratory studies have addressed this point and examined the
effects of dermal exposure. In these studies, rats were exposed to
hydrodesulfurized kerosine by skin application to determine the potential of
dermal contact to cause reproductive/developmental toxicity (OECD Guideline 421)
or neurotoxicity (TSCA Guidelines on subchronic inhalation and neurotoxicity
studies). These studies demonstrated that the highest dose level of kerosine does
not induce reproductive/developmental or neurotoxicity effects by skin exposure
in rodent studies. The dermal NOEL for HDS kerosine in rats was > or = 494 mg/kg
for both neurotoxicity, and reproductive/developmental toxicity.
PMID- 10189577
TI - A comprehensive evaluation of the carcinogenic potential of middle distillate
fuels.
AB - Middle distillate fuels (MDFs), which include jet fuel, kerosene, and diesel
fuel, are a class of hydrocarbons distilled from crude oil at approximately 350
700 degrees F (176-371 degrees C). Although MDFs generally do not contain
appreciable levels of potentially carcinogenic polycyclic aromatic compounds
(PACs), they have produced weak tumorigenic responses in mouse skin characterized
by low tumor yield and long latency. Recent studies demonstrated that the
tumorigenic effects of these MDFs were dependent upon chronic dermal irritation.
In the absence of skin irritation, tumors did not develop. Mechanistic studies
suggest that straight-run MDFs containing low levels of PACs cause skin tumors
through a nongenotoxic mechanism. MDFs cause chronic skin irritation and injury
with repeated application to the skin. They have been found to have little or no
activity in the modified Ames mutagenicity assay, lack tumor initiating activity,
and are active skin tumor promoters. It has been hypothesized that the
tumorigenic response to MDFs results from the promotion of preexisting,
spontaneously initiated cells. Two recent studies, a one-year tumor promotion
study and a two-year skin painting study, evaluated the role of skin irritation
on the tumorigenic activity of MDFs in mice. MDFs were applied in pure and
diluted forms to assess the effect of equal weekly doses of irritating and
nonirritating test materials. The tumorigenicity of straight-run MDFs correlated
to the level of skin irritation. No significant increase in tumor incidence
occurred under conditions that resulted in minimal skin irritation and injury.
These studies indicate that the tumorigenic activity of MDFs containing low
levels of PACs is secondary to chronic skin irritation. These materials should
not present a carcinogenic hazard in the absence of prolonged skin irritation.
PMID- 10189578
TI - Comparison of internal dose measures of solvents in breath, blood and urine and
genotoxic changes in aircraft maintenance personnel.
AB - Solvents and fuels are in widespread use both in civilian and military
populations. 1,1,1-trichloroethane (TCA), xylene, toluene, methyl ethyl ketone
(MEK) and methylene chloride are found in a variety of compounds including
degreasing agents, paints, coatings, pesticides and paint strippers. Toluene and
xylene are also found in fuels, which are complex mixtures of hundreds of agents.
The purpose of this investigation was twofold. The first was to determine the
optimum medium to measure internal dose of solvents comparing blood, urine and
breath. The second was to determine if low level exposures were associated with
genotoxic changes after a short-term exposure of fifteen or thirty weeks. To
accomplish the first goal a pilot study was initiated involving eight volunteers
who worked in aircraft maintenance including sheet metal, painting and assembly
mechanic jobs. Industrial hygiene measurements were evaluated over 30 working
days. Breath, blood and a 24-hour urine sample were collected twice to compare
internal dose parameters. To achieve the second goal, 58 newly hired subjects
were monitored prior to exposure and over 30 weeks to determine if there were
genotoxic changes as a result of solvent and/or fuel exposure as measured by
sister chromatid exchanges (SCEs) and micronuclei (MN). Exposure groups included
workers involved in sheet metal (fuel cell) activities, painting, fueling
operations and flight line. Results of the pilot study demonstrated that
industrial hygiene air samples and internal breath measures taken on the same day
were highly correlated for measuring TCA (r = 0.93) and toluene (r = 0.90) but
was not as well correlated for the other compounds. Breath measures were more
sensitive for measuring low level exposure than were either analytes in blood or
24-hour urine samples; these latter two measures were usually below the limit of
detection. A small but statistically significant increase in the frequency of
SCEs occurred after 30 weeks of exposure for sheet metal workers (p = 0.003) and
for painters (p = 0.05). The MN frequency in the sheet metal workers initially
showed a significant increase by 15 weeks, but by 30 weeks had decreased. Chance
occurrence of exposures to other occupational or non-occupational agents can not
be eliminated as a cause of the genotoxic results since between 58 and 93 total
analytes could be found in the breath of some aircraft maintenance personnel.
PMID- 10189579
TI - Quantitative posturagraphy as an alternative noninvasive tool for
alcohol/drug/chemical testing--preliminary thoughts.
AB - This article provides preliminary ideas regarding how the quantitative
posturagraphy technique can be used as an alternative noninvasive tool to
currently available blood/urine test for alcohol/drug/chemical exposure. It is
argued that the urine or blood level of any chemical is highly dependent on the
individual's metabolism without providing any insight into individual's task
performance abilities under exposure to neurotoxic chemicals. On the other hand,
the quantitative posturagraphy if carried out as proposed in this article will
provide quantitative data regarding individual's ability to maintain "safe"
upright balance while carrying out certain tasks. The proposed evaluation method
is simple, portable, quick, and noninvasive and has been found to be sensitive to
detecting low level solvent induced modifications in postural stability.
PMID- 10189580
TI - A computer program for conducting incinerator risk assessments.
AB - In 1994, the United States Environmental Protection Agency (USEPA) developed a
screening methodology for conducting indirect exposure risk assessments for
combustion facilities. The United States Army Center for Health Promotion and
Preventive Medicine currently utilizes this methodology in conjunction with other
USEPA guidance documents to perform human health risk assessments (HHRAs). The
HHRAs require the development of complex human health models using spreadsheet
software packages which estimate various media concentrations of contaminants in
the environment. Since the quality assurance/quality control procedures
associated with verifying the model's results are extremely time consuming, a
computer program was developed using Microsoft Excel to minimize the amount of
time needed. This discussion describes the 6 steps taken in developing this
computer program, which are: (1) understanding the problem; (2) establishing the
structure of each table in the spreadsheets; (3) developing an algorithm to solve
the problem; (4) writing code; (5) running the program; and (6) testing the
results. The automated process of having the computer predict health risk and
hazards for each potentially exposed individual saves a tremendous amount of time
because each calculated value is placed in the correct spreadsheet cell location.
In addition to the time needed to develop human health spreadsheets, this program
also minimizes the potential for reducing human error.
PMID- 10189581
TI - Characterization of risks posed by combustor emissions.
AB - Risk characterization is the final step of the risk assessment process as
practiced in the U.S. EPA. In risk characterization, the major scientific
evidence and "bottom-line" results from the other components of the risk
assessment process, hazard identification, dose-response assessment, and exposure
assessment, are evaluated and integrated into an overall conclusion about the
risks posed by a given situation. Risk characterization is also an iterative
process; the results of a specific step may require re-evaluation or additional
information to finalize the risk assessment process. Risks posed by atmospheric
emissions are an example of an involuntary human health risk which typically
receives a great deal of public attention. Characterization of the risks posed by
atmospheric emissions typically requires the use of mathematical models to
evaluate: 1) the environmental fate of emitted pollutants, 2) exposures to these
pollutants, and 3) human dose-response. Integration of these models results in
quantitative risk estimates. The confidence in a quantitative risk estimate is
examined by evaluating uncertainty and variability within individual risk
assessment components. Variability arises from the true heterogeneity in
characteristics within a population or an event; on the other hand, uncertainty
represents lack of knowledge about the true value used in a risk estimate. U.S.
EPA's 1997 Mercury Study will illustrate some aspects of the risk
characterization process as well as the uncertainty and variability encountered
in the risk assessment process.
PMID- 10189582
TI - Incorporation of potential for multimedia exposure into chemical hazard scores
for pollution prevention.
AB - We are reporting a chemical hazard score for pollution prevention, called the
Purdue score. The Purdue score provides a relative quantitative measure combining
a variety of chemical hazards into a single quantitative hazard weighting factor
for the non-expert to use. The main expected uses are to design safer products,
assist in implementing and measuring achievement in pollution prevention, and as
an adjunct for reporting Toxic Release Inventory data to the U.S. Government.
Scoring results are presented for 200 Superfund chemicals, rank ordered by the
worker hazard part of the score, by the environmental hazard part, and by
combined worker and environmental hazard scores. We have reviewed the extent to
which the Purdue score presently incorporates potential for multimedia pathway
and multiroute absorption exposure. Until other possible uses have been carefully
tested, peer-reviewed and published, users are advised to limit use of this
system to planning, implementing and measuring pollution prevention and to
enhancing the interpretation of Toxic Release Inventory data. The objective of
this report is to look at how the structure of this score handles exposure to
chemicals, both via multi-compartment pathways and multi-routes for contact or
absorption health damage, as well as how it handles habitat degradation by
chemicals. For all of these, the approach is built on inherent properties of each
chemical, which are true for all sites and scenarios. The biggest obstacle to
scoring is lack of measured chemical property data needed for scoring. We handle
missing data by regression, quantitative structure activity relationship
estimations, and a missing data default rule. The limitations of chemical hazard
scoring are reviewed. At present, there is no widely accepted single measure of
relative chemical hazard, against which to calibrate this hazard score for
accuracy, except experience from industrial use. However, despite limitations, we
suggest there is a strong value added for industry and society in availability of
a concise, simple-to-use measure of relative chemical hazard. The Purdue score
enables separate or combined consideration of chemical hazard to workers and to
the natural environment. The Purdue score has potential for major cost savings in
relative hazard ranking and business decision making regarding little-studied
organic chemicals, because of the extensive use of advanced property estimation
software. We conclude that there is societal need to warrant advanced development
of this risk management tool, which is now ready for pilot use by industry. The
Purdue score is mainly intended to assist and encourage businesses to implement
and measure pollution prevention-especially small businesses--in a cost-effective
way. The Purdue score relies strongly on sublethal toxicity, and there is
practical potential for it to be used with thousands of chemicals.
PMID- 10189583
TI - Development of toxicity criteria for petroleum hydrocarbon fractions in the
Petroleum Hydrocarbon Criteria Working Group approach for risk-based management
of total petroleum hydrocarbons in soil.
AB - The Total Petroleum Hydrocarbon Criteria Working Croup (TPHCWG) was formed in
1993 based on the observation that widely different clean-up requirements were
being used by states at sites that were contaminated with hydrocarbon materials
such as fuels, lubricating oils, and crude oils. These requirements were usually
presented as concentration of total petroleum hydrocarbon (TPH), and ranged from
10 to over 10,000 mg TPH/kg soil. Members of this multi-disciplinary group,
consisting of representatives from industry, government and academia, jointly
recognized that the numerical standard was not based on a scientific assessment
of human health risk and established the following goal for the effort: To
develop scientifically defensible information for establishing soil cleanup
levels that are protective of human health at hydrocarbon contaminated sites. The
approach developed by the TPHCWG for TPH hazard assessment consisted of dividing
the petroleum hydrocarbon material into multichemical-containing fractions with
similar fate and transport characteristics. These fractions were then assigned
fate and transport properties (volatilization factor, soil leaching factor, etc.)
and toxicity values (RfDs/RfCs) representative of the fraction. The actual site
specific hazard assessment and derivation of cleanup levels is accomplished by
analyzing sites to determine which fraction(s) is present and applying the
appropriate fate, transport and toxicity factors. The method used by this group
to determine TPH Faction specific toxicity criteria is a surrogate approach
intended to supplement the indicator approach. Indicators are single,
carcinogenic hydrocarbon compounds which are evaluated/regulated individually at
either the federal or state level. The TPHCWG surrogate approach utilized all
appropriate fraction specific toxicity data (single compound and
mixture/product), minus the carcinogenic indicator compounds, to derive the
fraction specific RfDs and RfCs. This hazard assessment method for petroleum
contaminated sites would be utilized where indicator compounds are not present or
are below/remediated to regulatory action levels. Derivation of the RfD/RfC
values for the n-hexane containing aliphatic C5-C8 fraction is examined in detail
to illustrate the underlying assumptions and use of existing data employed by the
TPHCWG to develop fraction specific toxicity criteria. Toxicity RfDs/RfCs for all
of the model fate and transport based fractions are also presented.
PMID- 10189584
TI - Calculation of human health risk-based screening levels (RBSLs) for petroleum.
AB - Hazardous waste site managers and regulators can decide easily whether site
contamination requires remediation to protect human health, but defining the
extent of cleanup is often an enormous challenge. When is the site clean enough
for human access and use? Risk assessment tools can be used to help answer this
question. One can calculate chemical-specific risk-based screening levels (RBSLs)
in environmental media (e.g. soil, water, and food) that correspond to
"acceptable" levels of risk. RBSLs can be calculated for individual chemicals and
chemical mixtures, specific to various exposure pathways. In calculating RBSLs,
one must account for the fact that people may be exposed to more than one
chemical by more than one exposure pathway. Fate and transport models may be
needed to predict how people might become exposed to site contamination in the
future. Examples RBSLs for non-cancer effects are calculated to illustrate the
utility and limitations of RBSLs for making risk-based decisions at petroleum
release sites.
PMID- 10189585
TI - Primer for evaluating ecological risk at petroleum release sites.
AB - Increasingly, risk-based approaches are being used to guide decision making at
sites such as service stations and petroleum product terminals, where petroleum
products have been inadvertently released to the soil. For example, the API
Decision Support System software, DSS, evaluates site human health risk along six
different routes of exposure. The American Society for Testing and Materials'
Risk-Based Corrective Action (RBCA) standard, ASTM 1739, establishes a tiered
framework for evaluating petroleum release sites on the basis of human health
risk. Though much of the risk assessment focus has been on human health risk,
regulatory agencies recognize that protection of human health may not fully
protect the environment; and EPA has developed guidance on identifying ecological
resources to be protected through risk-based decision making. Not every service
station or petroleum product terminal site warrants a detailed ecological risk
assessment. In some cases, a simple preliminary assessment will provide
sufficient information for decision making. Accordingly, the American Petroleum
Institute (API) is developing a primer for site managers, to assist them in
conducting this preliminary assessment, and in deciding whether more detailed
ecological risk assessments are warranted. The primer assists the site manager in
identifying relevant ecological receptors and habitats, in identifying chemicals
and exposure pathways of concern, in developing a conceptual model of the site to
guide subsequent actions, and in identifying conditions that may warrant
immediate response.
PMID- 10189586
TI - Field trials of antileprosy vaccines.
PMID- 10189587
TI - Comparative leprosy vaccine trial in south India.
AB - This report provides results from a controlled, double blind, randomized,
prophylactic leprosy vaccine trial conducted in South India. Four vaccines, viz
BCG, BCG+ killed M. leprae, M.w and ICRC were studied in this trial in comparison
with normal saline placebo. From about 3,00,000 people, 2,16,000 were found
eligible for vaccination and among them, 1,71,400 volunteered to participate in
the study. Intake for the study was completed in two and a half years from
January 1991. There was no instance of serious toxicity or side effects
subsequent to vaccination for which premature decoding was required. All the
vaccine candidates were safe for human use. Decoding was done after the
completion of the second resurvey in December 1998. Results for vaccine efficacy
are based on examination of more than 70% of the original "vaccinated" cohort
population, in both the first and the second resurveys. It was possible to assess
the overall protective efficacy of the candidate vaccines against leprosy as
such. Observed incidence rates were not sufficiently high to ascertain the
protective efficacy of the candidate vaccines against progressive and serious
forms of leprosy. BCG+ killed M. leprae provided 64% protection (CI 50.4-73.9),
ICRC provided 65.5% protection (CI 48.0-77.0), M.w gave 25.7% protection (CI 1.9
43.8) and BCG gave 34.1% protection (CI 13.5-49.8). Protection observed with the
ICRC vaccine and the combination vaccine (BCG+ killed M. leprae) meets the
requirement of public health utility and these vaccines deserve further
consideration for their ultimate applicability in leprosy prevention.
PMID- 10189588
TI - Quality control tests for vaccines in leprosy vaccine trial, Avadi.
AB - All the vaccines supplied for the large scale comparative leprosy vaccine trial
of ICRC bacilli, M.w, BCG plus killed M. leprae (candidate vaccines), BCG and
normal saline (control arms) at CJIL Field Unit, Chennai were tested for quality
control by the suppliers following the procedures laid down in the WHO protocol
for killed M. leprae. Quality control for BCG was carried out at BCG vaccine
laboratory as per protocol. Toxicity and sterility tests were done on all the
vaccine batches/lots received. As part of the quality control, bacterial count,
and protein estimation were also done. Studies showed that the bacterial content
and protein concentration were comparable with the original preparations.
Vaccines were free from micro-organisms, toxic materials and safe for human use.
Thus the quality of all vaccine preparations was satisfactory.
PMID- 10189589
TI - Identification of M.leprae in conjunctiva of leprosy patients using the superior
tarsal conjunctiva scrape technique.
AB - The technique of superior tarsal conjunctiva scrape was used for identifying
M.leprae in the conjunctiva in 56 leprosy patients (all of them multibacillary,
some untreated and others treated with multidrug therapy). The technique of
tarsal conjunctiva scrape was shown to be more suitable than conjunctival biopsy
for identifying lepra bacilli. This technique is also easier to perform and has
shown a statistical relation between bacilloscopical index of skin (BIsk) and
bacilloscopical index of tarsal conjunctiva (BIconj) values. Thus, if the bacilli
can be identified at tarsal conjunctiva we can assume greater systemic bacillary
load in the patients.
PMID- 10189590
TI - LDH isozymes with anomalous bands in semen of leprosy patients.
AB - Activity of LDH isozymes was evaluated electrophoretically on 7% acrylamide gel
in semen of 37 leprosy patients (15 with borderline, 12 with borderline
tuberculoid and ten with lepromatous leprosy) and ten fertile men of 30-45 years
of age. Significantly lower activities were recorded of LDH1 in all categories of
leprosy patients. Similarly, lowering of LDH2 activity was noticed in borderline
and lepromatous cases only, lowering of LDH4 activity in lepromatous cases only
and LDH5 activity was lowered in borderline leprosy patients. Lowest activity of
LDH3 and absence of LDHx were found in lepromatous leprosy. However, in
borderline tuberculoid patients, LDH3 and LDHx were significantly higher. This
exceptional increase in activity was found to be due to presence of additional
(anomalous) isozymes bands of LDH3, LDHx and LDH4 in 25% of borderline
tuberculoid patients. Additional bands of LDH3 have also been located in 40% of
the borderline leprosy patients.
PMID- 10189591
TI - Histoid leprosy with episcleral nodule--after MDT-MB.
PMID- 10189592
TI - Leprosy among hotel workers.
PMID- 10189593
TI - Why Mycobacterium leprae invades the eyes?
PMID- 10189594
TI - WHO meeting on the future role of leprosy training and/or research institutions,
Addis Ababa, February 25-26, 1998.
PMID- 10189595
TI - Living better longer through technology.
PMID- 10189596
TI - Towards a science of Alzheimer's disease management: a model based upon current
knowledge of retrogenesis.
AB - BACKGROUND: General relationships between dotage and infancy and childhood have
been acknowledged for more than two millennia. Recent findings indicate precise
relationships between functional, praxic, and feeding changes in the course of
the degenerative dementia of Alzheimer's disease (AD) and inverse corresponding
developmental sequences. Similar inverse relationships between AD and human
development can be described for cognition and language skills; for physiologic
measures of electroencephalographic activity, brain glucose metabolism, and
developmental neurologic reflex changes; and for the neuropathologic and
neuroanatomic progression of these processes. In AD, these processes may be
termed "retrogenesis." The relevance of the retrogenesis model for AD management
is explored. METHOD: The functional stages of AD can be translated into
developmental age equivalents that can be utilized to explicate observed changes
in the disease. RESULTS: The retrogenesis-based developmental age model can
usefully inform an understanding of the general care needs, emotional and
behavioral changes, and activity needs of the AD patient. This model must be
amended by necessary caveats regarding physical differences, variations in age
associated pathology, differences in social and societal reactions, and
differences in background between AD patients and their developmental age
"peers." CONCLUSIONS: Knowledge of retrogenesis and the developmental age of the
AD patient can form a nidus for the development of a nascent science of disease
management. Such a science must ultimately incorporate not only appropriate
caveats but also relevant universal human needs, such as those for dignity, love,
and movement.
PMID- 10189597
TI - Anxiety and its treatment in the elderly.
AB - A search for references relating to the treatment of anxiety disorders in the
elderly was made using the BIDS computerized database back to 1981, the Medline
computerized database back to 1983, and the PsycLIT computerized database back to
1974, together with a search of relevant citations. The profusion of clinical
recommendations was found to contrast with the lack of adequate supporting
controlled clinical trials. There was evidence of a trend away from the
benzodiazepine class of anxiolytics and an upsurge in interest in agents active
at the serotonin receptor, although with the possible exception of buspirone,
there is so far little research evidence for advocating use of the new agents in
the elderly. Psychological therapies may be useful for many types of anxiety in
the elderly, but their efficacy is also as yet unproven. Rational prescribing
recommendations for anxiety in this age group will require controlled clinical
trials incorporating a multiaxial approach to anxiety assessment, quality-of-life
measures, psychological and placebo controls, and adequate follow-up intervals.
PMID- 10189598
TI - Sleep complaints among the elderly: results from a survey in a psychogeriatric
outpatient clinic in Brazil.
AB - BACKGROUND: Sleep complaints are frequent in old age. These difficulties are
often associated with health-related problems, drug consumption, and the presence
of mental disorders. Nonetheless, only sparse information is available on the
clinical characteristics of elderly persons with insomnia. AIMS: (a) To evaluate
the prevalence of sleep problems among the elderly assessed in a psychogeriatric
outpatient clinic; (b) to evaluate the association between the use of sleep
tablets and sleep difficulties in this sample of patients. METHODS: One hundred
eighteen consecutive subjects were recruited from a psychogeriatric outpatient
service in Sao Paulo, Brazil. Their sleep pattern was systematically assessed
with the "sleep inventory," a questionnaire consisting of 31 items that evaluate
a number of sleep-related features. Clinical diagnoses followed the ICD-10
clinical descriptions and diagnostic guidelines. The number of drugs consumed by
patients was also recorded. RESULTS: Sleep complaints were highly prevalent
(59.3%), with early-morning awakening and nightmares being more frequent among
patients with a depressive disorder. The use of sleep tablets was reported by
37.3% of subjects, and was associated with subjective sleep difficulties (odds
ratio [OR] = 7.13, p = .008), difficulties falling asleep (OR = 7.33, p = .021),
and frequent awakening during the night (OR = 7.10, p = .040) in a logistic
regression analysis. CONCLUSION: Sleep dissatisfaction is frequent among
psychogeriatric outpatients. Subjects taking hypnotic drugs have more sleep
related complaints than those who do not. The clinical use of hypnotics may not
be very effective for the treatment of sleep-related problems in the elderly.
There is an urgent need for systematic prospective controlled studies to assess
the efficacy and safety of the various forms of treatment of insomnia in old age.
PMID- 10189599
TI - Suicide among the elderly in Honolulu County: a multiethnic comparative study
(1987-1992).
AB - Suicide rates for the elderly continue to be the highest for any age group.
Although these rates are known to be significant, little study has been given to
the ethnic variability associated with this phenomenon. This retrospective study
was undertaken to explore this issue and involved a review of the coroner's
reports for completed elder suicides (65 years of age or older) for Honolulu
County from 1987 through 1992 inclusive. The results showed a mean age of 75
years, with the highest incidence of completion in the 80+ age group. The
predominant method of suicide completion in this study group was found to be
hanging, followed by jumping, firearms, and poisoning. There were significant
gender and ethnic differences in the method of suicide completion. Almost half of
the sample saw a healthcare provider within the 6 months before their death.
Comparisons with other elder suicide studies are presented.
PMID- 10189600
TI - Depressive symptoms and depressive episodes in recently widowed older men.
AB - Older widowers have high rates of completed suicide but have rarely been the
subject of systematic inquiry. We investigated the prevalence of depressive
symptoms and major depressive episodes (MDEs) in recently widowed older men over
the first 13 months after bereavement. We employed a matched-pair longitudinal
design and recruited subjects from a suburban community population. Fifty-seven
recently widowed older men were identified from official death records and 57
matched married men were identified from the electoral roll. Subjects were
assessed for the presence of current DSM-III-R MDEs using the Composite
International Diagnostic Interview (CIDI), a fully structured psychiatric
interview. Widowers were assessed at 6 weeks after bereavement (T1) and 13 months
after bereavement (T2). Married men were assessed at similar intervals. At T1,
seven widowers (12.3%) and no married men were found to have CIDI cases of
current MDE. At T2, one widower (1.9%) and no married men were found to have CIDI
cases of current MDE. Current MDE was not predicted by a past history of
dysphoria. At T1, 14.0% (8/57) of widowers reported specific suicidal thoughts or
actions. At T2, 15.4% (8/52) of widowers reported suicidal thoughts or actions.
We conclude that health workers should monitor closely the clinical course of
MDEs in recently widowed older men. Routine inquiry about suicidal ideation
should be an essential component of the clinical assessment of recently widowed
older men.
PMID- 10189601
TI - Mnemonic training in older adults: effects of age, length of training, and type
of cognitive pretraining.
AB - OBJECTIVES: To improve performance with mnemonic techniques for remembering words
and proper names. DESIGN: For word recall, a 2 x 2 factorial in which type of
pretraining and length of training were between-subjects manipulations. For
proper name recall, a two-group design in which type of pretraining was
manipulated between subjects. SETTING: Community. PARTICIPANTS: 268 community
dwelling adults over the age of 55 years who wished to improve their memory.
MEASUREMENTS: Recall of words and proper names both before and after training in
mnemonics. INTERVENTION: Participants received a 2-week training course on two
mnemonic techniques, the method of loci for words and a name association
technique for proper names. RESULTS: There was no effect of the pretraining
manipulation on proper name recall. For word recall, however, a multiple
regression that included age indicated that the older-old participants benefited
more from a combination of comprehensive pretraining and extended mnemonic
training than did the younger-old. CONCLUSIONS: Increased training time coupled
with a comprehensive pretraining regimen can improve the performance of the older
old in using mnemonics; this improved performance cannot be attributed solely to
enhanced knowledge of the mnemonic.
PMID- 10189603
TI - Increasing our knowledge of the homebound elderly.
PMID- 10189602
TI - Comparative efficacy and safety of sertraline versus nortriptyline in major
depression in patients 70 and older.
AB - BACKGROUND: Few randomized, double-blind studies that examine antidepressant
treatment in patients 70 years and older are available. To provide additional
data on the safety and efficacy of antidepressants in this rapidly growing
population segment, a subgroup analysis of a larger sertraline vs. nortriptyline
elderly depression treatment study was performed. METHODS: Outpatients (N = 76)
who met DSM-III-R criteria for major depression with a minimum Hamilton
Depression Rating Scale (HAM-D) severity score of 18 were randomized to 12 weeks
of flexible dose treatment with sertraline (50-150 mg) or nortriptyline (25-100
mg). RESULTS: Both treatments significantly improved depression as measured by
the HAM-D and Clinical Global Impression scales. At Weeks 10, 12, and endpoint,
sertraline demonstrated a significantly greater reduction in depression severity
compared to nortriptyline as measured by improvement on the 24-item HAM-D (mean
adjusted change score of 14.8 vs. 7.6, respectively, at Week 12; p = .001). Sixty
five percent of sertraline-treated patients were responders by Week 12 (50% or
greater reduction from baseline in 24-item HAM-D score) compared to 26% of
nortriptyline-treated patients (p < .05). Sertraline treatment had a
significantly more positive effect, when compared to nortriptyline, across almost
all associated measures of cognitive function, energy, anxiety, and quality of
life and was better tolerated than nortriptyline, with a lower attrition
rate/side effect burden. CONCLUSION: The efficacy advantage of sertraline
appeared to be even greater in this subgroup of older patients drawn from a
larger treatment study of depression that included elderly individuals over the
age of 60.
PMID- 10189604
TI - Scholarship and research of allied health deans and directors.
AB - In 1997, a questionnaire was sent to 141 allied health deans or directors to: 1)
determine current research and scholarship, 2) ascertain institutional
expectations regarding scholarly activities, 3) characterize the institution's
research environment, 4) quantitate scholarship productivity by point assessment,
and 5) compare scholarship of administrators from research universities with that
of those at non-research four-year colleges and universities. Seventy-three (52%)
responded. Measures of research productivity included time spent in research,
numbers of publications and presentations, and grantsmanship. While spending two
thirds of their time in administrative duties, many deans and directors were
actively involved in scholarship. Since 1990, they had, as a group, produced 855
publications, made 1,348 presentations, and been awarded $38.3 million in total
funding. They did not differ significantly by employing institution (a research
institution or a non-research institution).
PMID- 10189605
TI - A national survey of current admission practices in selected allied health
educational programs.
AB - This study investigated the admission practices of selected allied health
programs, specifically considering the priorities placed on cognitive and
noncognitive factors. The extents to which diversity and a student's desire to
work in underserved areas are considered in the selection process were also
examined. Of 206 questionnaires mailed to accredited baccalaureate occupational
therapy, physical therapy, health information management, and respiratory therapy
programs, 144 were returned. The results indicate that allied health programs use
combinations of cognitive and noncognitive factors in selecting students for
admission. A higher priority is placed on overall grade-point average (GPA) and
GPA in foundation courses, whereas lower priorities are placed on the need for
diversity and a student's desire to work in underserved areas. The authors
discuss the implications of the findings and urge the rethinking of the
traditional selection method, which places applicants from ethnic/racial minority
backgrounds at a disadvantage.
PMID- 10189606
TI - Allied health professionals and attitudes toward teamwork.
AB - This study was conducted to determine whether allied health disciplines'
attitudes toward preparedness and willingness to participate in interdisciplinary
teams differed. A structured questionnaire was used to measure five factors:
orientation toward team problem solving, problem-solving confidence, preparedness
for interdisciplinary teams, attitudes toward interdisciplinary teams, and self
efficacy in contributing to interdisciplinary teams. There were 410 completed
questionnaires, for an overall return rate of 50%. Analysis of variance and
Scheffe post-hoc statistical tests were applied in analyzing the data. In
general, the respondents were positive for all of the factors. Medical
technologists indicated the least preparation for interdisciplinary teams,
whereas circulation technologists indicated the least confidence in contributing
to the teams. Persons who had participated in interdisciplinary teams were more
positive toward team problem solving and were certain of their abilities to
contribute to a problem-solving team. Implications for educators are discussed.
PMID- 10189607
TI - Multidisciplinary team dynamics in the production of problem-based-learning cases
in issues related to older adults.
AB - Two important goals in allied health education are to prepare future allied
health professionals to function as members of interdisciplinary teams and to
increase their awareness of issues related to the growing older adult population.
The responsibility for achieving these goals rests on the faculty and
administrators of allied health education programs, who may not themselves be
proficient in either of these domains. A multidisciplinary team of health
educators and administrators was brought together to produce six problem-based
learning (PBL) cases related to older adults. Members of the team represented a
variety of disciplines in health care, diverse philosophies of educational
development, a variety of roles in allied health education, and differing levels
of knowledge of issues related to older adults--parameters similar to those found
in the members of an interdisciplinary healthcare team. The methods by which this
multidisciplinary group functioned and the dynamics in attaining the goals of the
project are presented.
PMID- 10189608
TI - Interdisciplinary pilot project in a rehabilitation setting.
AB - This project qualitatively evaluated the planning, implementation, and outcome of
an interdisciplinary model of clinical education. Expectations of physiotherapy
(PT), occupational therapy (OT), and speech-language pathology (SLP) students and
clinicians were assessed to determine whether the model allowed for the
acquisition of the interdisciplinary knowledge and skills needed for current
practice. Students from OT (n = 5), PT (n = 3), and SLP (n = 1) undertook
normally scheduled five-to-eight-week clinical placements, beginning on the same
start date. All students were at intermediate or senior levels in their programs.
Discipline-specific activities were supervised by clinical instructors from the
disciplines. Interdisciplinary sessions during the first five weeks covered cross
disciplinary activities related to clinical reasoning, interviewing techniques,
professionalism, and communication skills for team reporting. Themes related to
the clinical experience were derived from student and supervisor responses to pre
and post-placement questionnaires, post-placement focus group interviews, and
student journals. The response to the model was positive. The students felt they
had gained insights into developing interdisciplinary skills, although they did
feel that some discipline-specific needs were not met. The instructors were less
enthusiastic but, given better planning and communication before the placement,
welcomed the opportunity to try it again.
PMID- 10189609
TI - The promise and pragmatism of interdisciplinary education.
PMID- 10189611
TI - The order of things: alternative medicine.
PMID- 10189610
TI - The multimedia power portfolio: creative strategy for core curriculum.
AB - To address today's rapidly changing health care environment, educational programs
for students in the health professions must also change by exploring new and
innovative ways to better prepare students for their future as members of the
health care team. This demand for change in allied health and nursing educational
programs comes at a time when institutions of higher education are faced with
shrinking funds. Therefore, creative efficient utilization of resources must be a
prime consideration when implementing new educational models.
PMID- 10189612
TI - Downregulation of RNase L inhibitor correlates with upregulation of interferon
induced proteins (2-5A synthetase and RNase L) in patients with chronic fatigue
immune dysfunction syndrome.
AB - Chronic Fatigue Immune Dysfunction Syndrome (CFIDS) is a disorder characterized
by debilitating fatigue associated with immunological abnormalities and cognitive
impairments. The recently cloned RNase L Inhibitor (RLI) gene encodes a specific
protein which is believed to regulate 2-5A synthetase and RNase L activity via
the formation of a latent heterodimeric protein complex. In the present study, we
investigated the levels of 2-5A synthetase, RNase L and RLI in patients with
CFIDS as compared to healthy controls. Quantitative Competitive PCR (Q/C PCR)
analysis showed a statistically significant decrease in RLI mRNA present in the
peripheral blood lymphocytes (PBL) of patients with CFIDS (n = 25, mean = 569,
S.E = 154) as compared to RLI mRNA level present in peripheral blood lymphocytes
(PBL) of healthy controls (n = 15, mean = 2296, S.E = 506; p < 0.0001). The
decrease in RLI mRNA in CFIDS individuals correlated directly with RLI and RLI:
RNase L protein ratio while showing an inverse relationship to the 2-5A
synthetase and RNase L activity. This RLI mRNA and protein deficiency in CFIDS
patients may explain the increase in activity of RNase L found in CFIDS patients.
The unidirectional decrease in RLI message and protein levels in CFIDS
individuals may contribute to the destabilization of the latent RLI:RNase L
heterodimeric protein complex, resulting in the excessive activation of RNase L
shown in this study. The increased activation of RNase L may result in an
increased cellular RNA turnover and subsequent inhibition of protein synthesis;
thus resulting in general fatigue, myalgia muscle weakness and other
symptomatologies shown in CFIDS patients. Furthermore, this data supports the
hypothesis that the antiviral 2-5 oligoadenylate synthetase (2-5OAS)
overexpression in individuals with CFIDS correlates with an increase in RNase L
activity and with a decrease in RNase L inhibitor.
PMID- 10189613
TI - Anti-soluble interleukin-2R alpha combinations measure different epitopes:
comparison between different anti-sIL-2R alpha antibody combinations and a newly
developed in-house sIL-2R alpha sandwich ELISA.
AB - Cytokines are a group of low molecular weight glycoproteins important in cellular
signaling for various responses such as activation and proliferation. They
separate the cellular responses into Th1 and Th2 pathways, where each pathway
releases its own cytokine group. Interleukins are an important section of the
cytokine group and consist of a number of members with their respective receptors
such as interleukin-2 and interleukin-2 receptor (IL-2 and IL-2R, respectively).
In this study, a soluble interleukin-2 receptor alpha (sIL-2R alpha) sandwich
ELISA was developed and tested with different samples. This method was compared
with other mono- and polyclonal antibodies that measure sIL-2R alpha molecule
using the same subjects and recombinant sIL-2R alpha. The results showed that
different antibody combinations measure different epitopes on the receptor
molecule.
PMID- 10189614
TI - An analysis of the value of some antigen-antibody interactions used as diagnostic
indicators in a treponemal Western blot (TWB) test for syphilis.
AB - Densiometric quantitation and spreadsheet normalization were used to refine the
parameters defining a treponemal Western blot (TWB) test for syphilis. Initially
using 84 defined reactive and 105 defined non-reactive sera, we determined that
the immune response to the 17 kDa antigen was the most critical of the following
three candidate test determinants: the 47 kDa, 17 kDa and 15.5 kDa bands. In a
second study using 124 cases of clinically diagnosed syphilis and 354 "normal"
donors, a diluted serum sample was included as a minimal reactive control for the
17-kDa immune response. Reactivity to all three test determinants was obligatory
for a test result to be interpreted as positive. Of the 124 cases of syphilis, 7
were nonreactive by TWB (sensitivity = 94%); of the 354 normal donors, 7 tested
reactive (specificity = 98%). Forty (11%) normal serum samples had detectable but
less than minimal reactivity to the 17 kDa band. Frequencies of immune response
to a larger group of 12 antigens were tallied for the 124 clinically diagnosed
cases of syphilis and an equal subset (124) of the normal group. In the normal
subset, 72% and 52% of the samples had detectable reactivity to the 47 and 15.5
kDa antigens, respectively, while 10%, 5% and 3% reacted with the 17, 24 and 44.5
kDa antigens, respectively. Follow-up TWB testing of the clinically diagnosed
cases revealed that previously untreated patients with primary or secondary
syphilis were more likely to a show decrease in TWB reactivity than patients with
latent symptoms who had been treated previously. As a diagnostic indicator of
syphilis, the 17-kDa antigen was found to have the best combined attributes of
sensitivity and specificity. Although, the highly specific 44.5 kDal and 24 kDal
bands were often redundant as diagnostic indicators they are useful for the
interpretation of borderline results. In addition, absence of the highly
sensitive 47 and 15.5 kDa indicators should be useful in resolving some problem
diagnoses.
PMID- 10189615
TI - The neurobiology of ECT: the road ahead.
PMID- 10189616
TI - The anticonvulsant hypothesis of the mechanisms of action of ECT: current status.
AB - Electroconvulsive therapy exerts a variety of anticonvulsant effects. The linkage
between specific anticonvulsant effects and the efficacy of ECT is examined in
relation to changes in seizure threshold, seizure duration, and seizure
expression, and alterations in cerebral blood flow (CBF) and metabolism, and in
EEG slow-wave activity. New findings are presented that the magnitude of the
change in seizure threshold over the ECT course is associated with therapeutic
outcome, particularly with right unilateral (RUL) ECT. New findings also indicate
that the change in seizure threshold covaries with the magnitude of global
reductions in CBF over the treatment course, is inversely related to some
inhibitory aspects of seizure expression, and is independent of the cumulative
decrease in seizure duration. Considerable evidence has accrued associating the
anticonvulsant and antidepressant effects of ECT. However, critical experiments
should be conducted in which the effects of augmenting and blocking
anticonvulsant actions are studied in relation to efficacy.
PMID- 10189617
TI - EEG correlates of the response to ECT: a possible antidepressant role of brain
derived neurotrophic factor.
AB - Studies on the relationship of electroencephalographic (EEG) data to the
therapeutic response to electroconvulsive therapy (ECT) have been carried out
since the 1940s, but for many years they did not yield any consistent correlates.
Recent studies, however, are providing a growing body of evidence of
relationships between the antidepressant response to ECT and both the ictal
(recorded during ECT seizures) and interictal (recorded during waking) EEG. These
studies appear to be consistent in pointing to the importance of
electrophysiologic changes in the prefrontal cortex as a potential mediator of
the antidepressant response to ECT. The available findings are reviewed and
discussed in light of recent neurophysiologic and neuropsychiatric research,
including that related to neurotrophic factors.
PMID- 10189618
TI - Repetitive transcranial magnetic stimulation as a neuropsychiatric tool: present
status and future potential.
AB - Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising
therapeutic intervention in the treatment of affective disorders. The differences
in the type of electrical stimulation required for therapeutic efficacy by rTMS
and electroconvulsive therapy (ECT) are discussed. In contrast to ECT, rTMS would
not appear to require the generation of a major motor seizure to achieve
therapeutic efficacy. Accordingly, it carries the potentially important clinical
advantages of not requiring anesthesia and of avoiding side effects such as
transient memory loss. Preclinical studies on long-term potentiation (LTP) and
long-term depression (LTD) in hippocampal and amygdala slices, as well as
clinical data from neuroimaging studies, have provided encouraging clues for
potential frequency-dependent effects of rTMS. Preliminary evidence from position
emission tomography (PET) scans suggests that higher frequency (20 Hz)
stimulation may increase brain glucose metabolism in a transsynaptic fashion,
whereas lower frequency (1 Hz) stimulation may decrease it. Therefore, the
ability of rTMS to control the frequency as well as the location of stimulation,
in addition to its other advantages, has opened up new possibilities for clinical
explorations and treatments of neuropsychiatric conditions.
PMID- 10189619
TI - Neuropeptides and electroconvulsive treatment.
AB - Neuropeptides: corticotropin releasing factor (CRF), neuropeptide Y (NPY) and
somatostatin (STS) have been associated with depression and anxiety, while
neurotensin (NT), calcitonin gene-related peptide (CGRP) and tachykinins
[neurokinin A (NKA) and substance P (SP)] are presumed to also play a role in the
function of the dopaminergic system. Moreover, investigations in the past decade
have shown that psychotomimetics and antipsychotic drugs as well as lithium
affect brain synthesis, tissue concentrations, and release of some neuropeptides.
In view of the above, experiments were carried out to explore whether changes in
neuropeptides constitute one of the mechanisms of action of electroconvulsive
treatment (ECT). Human cerebrospinal fluid (CSF) was studied before and after
ECT, and brains from healthy and models of depression rats were investigated in
electroconvulsive stimuli (ECS)-treated and sham-treated animals. The major
findings were that a series of ECTs, in parallel to clinical recovery, increased
CSF concentrations of NPY-like immunoreactivity (-LI), STS-LI, and CRF-LI, and in
one study endothelin-LI. A series of ECS, but not a single treatment,
reproducibly elevated concentrations of NPY-LI, NKA-LI, and STS-LI--but not NT
LI, SP-LI, galanin-LI, or CGRP-LI--in hippocampus, frontal cortex, and occipital
cortex. No changes were measured in other regions, e.g., striatum. NPY and STS
mRNAs were also increased indicating that ECS affects peptide synthesis.
Generalized seizures induced by, e.g., kainic acid or pentylenetetrazole, had
similar effects on neuropeptides. The changes persisted for at least 1 week after
the last treatment. Pretreatment with compounds reducing seizures, such as
benzodiazepines and MK-801; had no effect on magnitude of neuropeptide changes
although the seizure duration was decreased by > 50%. On the basis of these
findings, it is suggested that neuropeptides are involved in ECT's mechanisms of
action. Since ECT is therapeutically efficient in both schizophrenia and
depression and, taking into account that antipsychotic drugs and psychotomimetics
as well as lithium selectively affect some neuropeptides, it is hypothesized that
distinct combinations of neuropeptide and monoamine changes in selected neuronal
populations constitute the underpinnings of ECT's effects on specific disease
symptoms, conceivably independent of diagnosis.
PMID- 10189620
TI - The role of TRH and related peptides in the mechanism of action of ECT.
AB - Thyrotropin-releasing hormone (TRH) has been known anecdotally to produce
antidepressant (AD) effects since the 1970s. Recent clinical reports have shown
that intrathecal administration of TRH can more reliably induce remissions of
major depression that last for 2-3 days. Although clinically impractical, it is
important to note that these remissions are rapid within hours, and they survive
at least 1 night's sleep. This review summarizes and integrates clinical and
preclinical research on TRH and related peptides, which have regulatory effects
in the limbic forebrain. Electroconvulsive shock (ECS) in rats induces synthesis
of TRH in multiple subcortical limbic and frontal cortical regions, which are
known, in humans, to be involved in both depression and in sleep. The increases
in TRH and related peptides are regionally specific. The quantitative TRH
increases in individual limbic regions have been correlated with the amount of
forced swimming done by the individual animal after ECS (forced-swim test of AD
effects). Intraperitoneal TRH also gives a positive response in this test, as do
all effective AD medications. By considering neurobiological phenomena in
depression and sleep, it is possible to outline a role for TRH and related
peptides that may assist in the understanding both of depression and of the
depressogenic effect of sleep in depressively vulnerable people. It is concluded
that TRH and related peptides are likely to play a significant role in the
inhibition of glutamatergic subcortical limbic neurons, which may be hyperactive
in depression. Electroconvulsive therapy is believed to act, in part, by
augmenting this inhibition. AD medications are believed to act indirectly, by
activation of a subset of GABAergic interneurons, which then inhibit the
pathologically hyperactive glutamatergic limbic neurons. Continued exploration of
TRH and related peptides will be essential for further progress toward the
control of these debilitating and often lethal diseases.
PMID- 10189621
TI - Electroconvulsive therapy as an anticonvulsant: a possible role of neuropeptide Y
(NPY).
AB - Seizure threshold increases during a series of electroconvulsive therapy (ECTs).
Based on assumptions that the effect of ECT may be related to its anticonvulsant
effect we were interested in identifying transmitters that are activated by the
treatment and play an anticonvulsant role. Animal studies reveal that
neuropeptide Y (NPY) neurotransmission is increased by repeated electroconvulsive
shock (ECS), and NPY has been found to inhibit glutamate-mediated synaptic
transmission in the rat hippocampus. The increase of NPY gene expression in
highly sensitive areas of the rat hippocampus (dentate gyrus) and piriform cortex
accompanied by a reduction of NPY binding sites in the same regions after ECS
supports this notion. Further studies have shown that NPY exerts a seizure
suppressing activity of NPY after kainic acid injections in vivo. Taken together
the present series of experiments in rats strongly points to the seizure
suppressing properties of NPY and suggests that this peptide may be involved in
the seizure threshold increase during effective ECT in humans.
PMID- 10189622
TI - Looking at environmental justice from an environmental health perspective.
AB - Although scientific evidence is scarce and uneven, there are mounting concerns
that environmental health risks are borne disproportionately by members of the
population who are poor and nonwhite. From an environmental health perspective,
research to reduce critical uncertainties in health risk assessment must
necessarily be at the heart of efforts to evaluate and resolve issues of
environmental justice--helping to define the dimensions of the problem,
understand its causes, and identify effective and efficient solutions. The full
range of environmental health sciences, including exposure analysis,
epidemiology, toxicology, biostatistics, and surveillance monitoring, is needed
to build a strong scientific foundation for informed decision making. This is the
best and surest way to promote health and safety for all members of our society,
regardless of age, ethnicity, gender, health condition, race, or socioeconomic
status.
PMID- 10189623
TI - Science and policy implications of defining environmental justice.
AB - Although 'environmental justice' is an increasingly important issue for policy
makers and researchers, it remains for many a vague and abstract notion that is
hard to define in practical, real-world terms. Part of the problem is that
environmental justice is a complex, multidimensional construct that cannot easily
be defined. Our aim in this article is to identify fundamental dimensions of
environmental justice and highlight the resulting questions that are an inherent
part of putting principles into practice. We argue that to have a constructive
and informed debate about this emotionally charged topic, it is necessary to have
a clear and workable definition of environmental justice. We do not propose our
own definition, but instead point out that there are many possible legitimate
definitions depending on one's beliefs, opinions, and values. The central point
is not that a particular definition is right or wrong, but rather than choosing a
definition has distinct implications for the formulation, implementation, and
evaluation of both policy and science. These critical choices should be made
explicit so that public dialogue can focus on the substance of this important
policy issue.
PMID- 10189624
TI - GIS-based measures of environmental equity: exploring their sensitivity and
significance.
AB - In order to determine whether principles of environmental justice have been
violated, a large number of empirical studies have been carried out to ascertain
whether minority and low-income populations are disproportionately exposed to
industrial pollution. This study provides a comparative evaluation of two
commonly employed proximity measures in GIS-based environmental equity
assessment, examining their influence on the results of the analysis, and
proposes a methodology for evaluating the significance of these results. 1990
census data on population characteristics and data from the 1995 EPA's toxic
release inventory (TRI) for the City of Minneapolis, MN are used. These results
also allow a preliminary assessment of environmental equity/inequity in potential
exposure to airborne toxic chemicals for racial minorities, poor people and
children in Minneapolis. In the third part of the paper we develop and employ a
geographic randomization methodology for assessing the significance of these
results.
PMID- 10189625
TI - An examination of race and poverty for populations living near industrial sources
of air pollution.
AB - This study examines the sociodemographic characteristics of people living near
industrial sources of air pollution in three areas of the United States: (1) the
Kanawha Valley in West Virginia: (2) the Baton Rouge-New Orleans corridor in
Louisiana: and (3) the greater Baltimore metropolitan area in Maryland. Using
data from the 1990 Toxics Release Inventory (TRI) and the 1990 Census, we analyze
relationships between variables assumed to be independent, such as location of
single or multiple industrial emission sources, and the dependent variables of
race (black/white) and poverty status (above/below poverty level). Results from
all three study areas are consistent and indicate that African Americans and
those living in households defined to be below the established poverty level are
more likely, on average, to live closer to the nearest TRI facility and to live
within 2 miles of multiple TRI facilities. Conversely, whites and those living in
households above the poverty level are more likely, on average, to live farther
from the nearest TRI facility and to live within 2 miles of fewer facilities,
compared to African Americans and poor people.
PMID- 10189626
TI - National human exposure assessment survey (NHEXAS): exploratory survey of
exposure among population subgroups in EPA Region V.
AB - The National Human Exposure Assessment Survey (NHEXAS) provides a rich database
of exposure and environmental measurements for persons living in EPA Region V
(Great Lakes). Demographics (e.g., gender, minority status, age, income, and year
home built) between U.S. Census data and the overall Region V sample were
compared and showed good agreement. This representative sample was used to
conduct an exploratory investigation of selected subpopulations that might
exhibit higher exposures, on average, to volatile organic chemicals (VOCs) such
as benzene, chloroform, etc.; inspirable particles; and metals (e.g., lead,
arsenic, etc.) than the general population in Region V. Means and medians were
the metrics of comparison. Personal air exposures for p-dichlorobenzene were
significantly higher in adults (> 21 years old) than in children (1-14 years old)
(median: below detection limit vs. 0.87 microgram/m3, p = 0.0005), while a trend
toward higher levels of arsenic exposure in children than adults was observed
(median: 1.13 vs. 0.8 ng/m3, p = 0.083). A trend towards higher personal air
exposure to lead for minorities vs. nonminorities was evident (median: 26 vs. 12
ng/m3, p = 0.066), but personal exposure to 1,1,1-trichloroethane tended to be
higher in nonminorities (mean: 22 vs. 3.7 micrograms/m3, p = 0.081). Dietary
exposure to arsenic from solid foods was significantly higher in adults than
children (mean: 21 vs. 7.1 micrograms/kg, p = 0.0001; median: 10 vs. 5.6
micrograms/kg, p = < 0.001), and for cadmium it was higher for nonminorities than
minorities (median: 18 vs. 15 micrograms/kg, p = 0.023). In contrast, the dietary
intake for arsenic, which is based on body weight, was significantly higher in
children than adults (mean: 1.72 vs 1.38 micrograms/kg-1 day-1, p = < 0.0001;
median 1.02 vs. 0.83, p = < 0.0001). Dietary exposure to chromium in beverages
tended to be higher in minorities than nonminorities (median: 16 vs. 13
micrograms/kg, p = 0.017). Lead levels in surface dust wipes tended to increase
with the age of the home (mean: 128 micrograms/g in homes built since 1980 to
1075 micrograms/g in homes built before 1940; median: 93 to 236 micrograms/g,
respectively). These findings were consistent with the observation that for
persons living in older homes personal air exposures to lead are elevated
compared to persons living in recently built homes (median: 12 ng/m3 in homes
built since 1980, vs. 24 ng/m3 in homes built before 1940, p = 0.043).
PMID- 10189627
TI - Environmental justice and statistical summaries of differences in exposure
distributions.
AB - Recent regulatory action requires the assessment of environmental justice
(equitable protection from the burdens of environmental hazards across
sociodemographic subpopulations) in the siting of hazardous waste sites, and
prioritization of environmental remediation efforts. Assessments of environmental
justice require linking exposure, demographic, and health data. The geographic
nature of the data makes the use of geographic information systems attractive for
environmental justice assessments. Typical geographic assessments compare the
composition of 'exposed' populations, while typical statistical assessments focus
on differences in health outcomes between population subgroups, possibly adjusted
for exposure. We outline an alternate approach based on summarized differences
between exposure distributions within each population subgroup. We illustrate how
such summaries provide a tool for site evaluation (e.g., defining exposure
inequities resulting from locating a new potential hazard at any of a number of
possible sites). In addition, we describe summaries, based on dose-response
relationships, to describe risk differences imposed by the observed exposure
differences. Reported toxic emissions from Allegheny County, Pennsylvania
illustrate the approach.
PMID- 10189628
TI - Assessing environmental justice using Bayesian hierarchical models: two case
studies.
AB - Sound statistical methodology for assessing environmental justice is clearly
needed, but has been slow to develop. In this paper, we investigate the use of
hierarchical Bayesian methods for combining disparate sources of environmental
data featuring complex correlations over both space and time. After a brief
review of the Bayesian approach and its specific application to disease mapping
problems, we illustrate two case studies. The first to these investigates the
effect of a certain nuclear fuel reprocessing facility in Ohio on the lung cancer
rates in the counties that surround it, while the second concerns the relation
between air quality (especially in terms of ambient ozone levels) and pediatric
emergency room visits due to asthma in the Atlanta metro area. We close by
summarizing the method's implications for environmental justice, as well as
future methodological and applied work.
PMID- 10189629
TI - The development of animal behavior: from Lorenz to neural nets.
AB - In the study of behavioral development both causal and functional approaches have
been used, and they often overlap. The concept of ontogenetic adaptations
suggests that each developmental phase involves unique adaptations to the
environment of the developing animal. The functional concept of optimal
outbreeding has led to further experimental evidence and theoretical models
concerning the role of sexual imprinting in the evolutionary process of sexual
selection. From a causal perspective it has been proposed that behavioral
ontogeny involves the development of various kinds of perceptual, motor, and
central mechanisms and the formation of connections among them. This framework
has been tested for a number of complex behavior systems such as hunger and
dustbathing. Imprinting is often seen as a model system for behavioral
development in general. Recent advances in imprinting research have been the
result of an interdisciplinary effort involving ethology, neuroscience, and
experimental psychology, with a continual interplay between these approaches. The
imprinting results are consistent with Lorenz' early intuitive suggestions and
are also reflected in the architecture of recent neural net models.
PMID- 10189630
TI - Multiple factors in the evolution of animal coloration.
AB - Many of the subjects about which biologists disagree concern the interpretation
of function. Morphological, physiological and behavioral characters can
simultaneously serve several various functions, all of which are subject to
natural selection. These may operate synergistically, but when two produce
opposing effects, the one possessing the greater survival value at the time is
selected. Often a compromise between several different evolutionary functions
results. When the functions under consideration are viewed from a wider angle, a
synthesis between differing opinions can sometimes be achieved and a greater
understanding of the phenomenon obtained. It should be remembered that, even if
an adaptation is invoked for only a brief time during the life of its possessor,
it might well be selected merely because of its transient value then. This
contribution is not a review, nor is it concerned with the biochemistry and
physiology of pigmentation. Rather, it is a discussion of some of the diverse
functions that have been ascribed to animal colours. A few typical examples are
considered, chosen mainly from among tropical animals including human beings.
PMID- 10189631
TI - A plea for preservation of the middle turbinate during dacryocystorhinostomy.
PMID- 10189633
TI - Frontal periosteum as an exposed orbital implant cover.
AB - PURPOSE: To describe the surgical technique of harvesting frontal bone
periosteum, through an eyelid-crease incision, for coverage of orbital implants.
METHODS: A retrospective review of the medical records of 15 patients who
underwent the procedure. RESULTS: Eleven patients had surgery to cover exposed
orbital implants, whereas in 4 patients the periosteal graft was used as an
implant cover during enucleation. Periosteal grafts as large as 25 mm in diameter
can be harvested. Recurrent exposure developed in 2 patients who had complicated
histories of local trauma. One of these patients required a secondary dermis-fat
graft, and the other experienced spontaneous granulation. The remaining 13
patients had excellent results without complications. CONCLUSION: Harvesting
frontal bone periosteum, through an eyelid-crease incision, for orbital implant
coverage is a relatively straightforward surgical technique. The procedure can be
performed in the office under local anesthesia and yields excellent results.
Recurrent exposure occurred only in 2 patients with histories of significant
local trauma.
PMID- 10189632
TI - Exposure of expanded polytetrafluoroethylene-wrapped hydroxyapatite orbital
implant: a report of two patients.
AB - PURPOSE: Hydroxyapatite (HA) spheres used to replace volume after an enucleation
are often wrapped with autologous tissue before orbital implantation. Man-made
materials are less expensive and pose no risk for viral transmission. The use of
expanded polytetrafluoroethylene (ePTFE) to wrap HA spheres was evaluated.
METHODS: The medical records of 2 consecutive patients who underwent
uncomplicated implantation of an HA sphere wrapped in ePTFE were reviewed.
RESULTS: An unusual reaction to the ePTFE material that was nonresponsive to
topical or systemic antibiotic therapy developed in these 2 patients. Eventual
wound erosion and bacterial infection of the implant necessitated its removal.
CONCLUSIONS: Although well tolerated in other surgeries, ePTFE, when used to wrap
HA spheres and placed into the orbit, may cause persistent conjunctival
discharge, pyogenic granuloma formation, and eventual wound erosion. Therefore,
the use of this material to wrap HA spheres is not recommended.
PMID- 10189635
TI - Distribution of adrenergic receptor subtypes in the retractor muscles of the
upper eyelid.
AB - PURPOSE: To identify adrenergic receptor subtypes and their relative distribution
in the retractor muscles of the upper eyelid, the levator palpebrae superioris,
and the Muller muscle. The pattern of distribution of these receptors in the
Muller muscle was further compared in patients with dysthyroid eyelid retraction
and in normal subjects. METHODS: Muller muscle specimens were collected from 19
patients undergoing ptosis correction and from 8 patients undergoing repair of
dysthyroid eyelid retraction. Immunohistochemical staining for alpha 1-, alpha 2
, beta 1-, and beta 2-adrenergic receptors was performed using antihuman rabbit
polyclonal antibodies. RESULTS: alpha 2-Adrenergic receptors were the predominant
subtype in the Muller muscle, and beta 1-adrenergic receptors were the
predominant subtype in the levator muscle. There was no significant difference in
the staining pattern between specimens collected from patients with dysthyroid
eyelid retraction and those from normal subjects. CONCLUSIONS: The interaction
between the alpha 2 and beta 1 receptors in the upper eyelid retractor muscles
may be important in the control of the upper eyelid position and may contribute
to the development of dysthyroid eyelid retraction. Specific alpha 2 antagonists
could be developed and may be effective pharmacologic agents for the treatment of
eyelid retraction.
PMID- 10189634
TI - Clinical factors influencing periocular surgical defects after Mohs micrographic
surgery.
AB - PURPOSE: To determine if the surgical defect after excision of periocular skin
cancers can be predicted preoperatively. METHODS: Review of medical records of
patients who underwent excision of periocular skin cancers between 1990 and 1995.
RESULTS: Two hundred sixty-four patients (157 men, 107 women) with a total of 281
malignant tumors were treated. Basal cell carcinoma accounted for 92.2% of the
tumors, whereas squamous cell carcinoma constituted 6.4% of lesions. The lower
eyelid and medial canthus were the most frequent sites of involvement. Data
analysis was conducted on tumor size, cell type, location, and the Mohs stages
and sections that were required for cure. Morpheaform basal cell carcinomas
required the most Mohs stages and sections and resulted in the largest excisional
defects when compared with clinical tumor dimensions. The lateral canthus had the
fewest tumors, but lesions in this area resulted in the largest excisional
defects (mean, 9.5 cm2) when compared with lesions of the medial eyelid (p =
0.35). The average size of the defect after Mohs excision of basal cell carcinoma
was 4.2 to 4.6 times the original clinical tumor size. For morpheaform basal cell
carcinoma, however, the average excisional defect was 6.1 times larger.
Conversely, the average defect after excision of squamous cell carcinoma was only
2.6 times as large as the original clinical tumor size. CONCLUSIONS: These data
are useful in predicting the size of a defect after Mohs excision of periocular
skin cancer, based on the original clinical tumor size.
PMID- 10189636
TI - Congenital, paradoxical lower eyelid retraction on upgaze.
AB - PURPOSE: Active lower eyelid retraction on upgaze is a rarely described finding.
The purpose of this study is to describe the clinical and operative findings in
two patients with this unique eyelid movement disorder. METHODS: The authors
identified active, unilateral lower eyelid retraction on upgaze in two patients
who had no other ocular or systemic abnormalities. RESULTS: Surgical extirpation
of the lower eyelid retractor complex was carried out in both cases. During one
of the procedures, performed under local anesthesia, the lower eyelid retractors
were observed to retract actively on upgaze. Postoperatively, lower eyelid
retraction on upgaze was not present in either case. CONCLUSIONS: The authors are
aware of only one other case report describing active, paradoxical lower eyelid
retraction on upgaze. The mechanism of eyelid retraction in this previous report
and in the two patients described herein is not known. The authors postulate that
these unique cases may represent a previously unrecognized form of congenital,
aberrant innervation of the oculomotor nerve.
PMID- 10189638
TI - Lacrimal sac diverticula associated with a patent lacrimal system.
AB - PURPOSE: To describe the clinical features of lacrimal sac diverticula. METHODS:
Orbital masses were evaluated in 3 patients. One patient had a large tumor
extending from the medial orbit associated with upward globe displacement, one
had a mass inferior to the medial canthus, and one had an inflamed mass in the
right lower lid. Two of the patients had no history of chronic epiphora, sinus
disease, or nasal trauma. In all patients, irrigation demonstrated lacrimal
drainage system patency. RESULTS: Surgical exploration confirmed the diagnosis of
lacrimal sac diverticulum in all patients. Two diverticula were associated with a
dacryolith. Each patient was successfully managed with excision of the
diverticulum and dacryocystorhinostomy. CONCLUSIONS: Lacrimal sac diverticula
should be considered in the diagnosis of medial orbital tumors, and computed
tomography is useful in the diagnosis of lacrimal sac diverticula.
PMID- 10189637
TI - Follow-up of patients with essential blepharospasm who underwent eyelid
protractor myectomy at the Mayo Clinic from 1980 through 1995.
AB - PURPOSE: To determine the efficacy of eyelid protractor myectomy (subtotal
excision of the orbicularis oculi, the corrugator supercilii, and the procerus
muscles) for the treatment of essential blepharospasm, and to evaluate the need
for and the effectiveness of botulinum toxin (BT) injections in these patients.
METHODS: The medical records of all patients who underwent eyelid protractor
myectomy at the Mayo Clinic (Rochester, MN) from 1980 through 1995 were reviewed.
The Health Status Questionnaire was used to assess overall medical and mental
health, and a questionnaire specific to eyelid spasms was developed. RESULTS:
Fifty-four white patients, of whom 32 (59%) were women, underwent myectomy. The
average age at diagnosis of essential blepharospasm was 64 years (median, 65
years; range, 43 to 84 years), whereas the average age at the time of myectomy
was 66 years (median, 66 years; range, 51 to 85 years). Of the 14 patients who
were treated with BT injections before myectomy, the average interval between the
initial injection and surgery was 21 months (median, 20 months; range, 2 to 51
months). Patients who had been treated with BT injections before myectomy were
more likely to receive injections postoperatively than were those patients who
had not been treated with BT (p < 0.001). Twenty patients were treated with BT
injections after myectomy; the overall probability of receiving BT five years
after surgery was 46%. Time from myectomy to treatment with BT varied
considerably; mean, 880 days; median, 659 days; range, 3 to 4221 days.
Postoperative follow-up for those patients who did not receive BT after myectomy
ranged from 2 to 5935 days (mean, 2354 days; median, 1722 days). Although the
probability of receiving BT injections after myectomy was not associated with age
or sex, there was a significant association with the time interval during which
the myectomy had been performed (related to the availability of BT as an
adjunctive therapy). Of the 41 patients who were alive when the study was
conducted, 32 (78%) completed a follow-up survey. Thirty of those (94%) said
myectomy provided short-term and long-term benefits. Of the 11 patients who
received BT injections before and after myectomy, six (55%) said the toxin was
more effective in ameliorating eyelid spasms after surgery and four (36%)
required injections less frequently after myectomy. Results from the Health
Status Questionnaire showed no significant differences between patients who
underwent myectomy and control subjects. CONCLUSIONS: Eyelid protractor myectomy
provides subjective benefit to patients with essential blepharospasm and
decreases the long-term need for BT injections in approximately 50% of these
patients. Although the probability of receiving postoperative BT paralleled its
availability, patients who received both preoperative and postoperative BT
perceived either increased efficacy of the toxin injections, longer-lasting
effects, or both, after myectomy. Patients with severe disability from
blepharospasm benefited more from myectomy than did patients with relatively mild
symptoms.
PMID- 10189639
TI - Correlation of orbital computed tomographic findings with office probing and
irrigation in 17 patients after successful and failed dacryocystorhinostomy.
AB - PURPOSE: To investigate the role of orbital computed tomography (CT) in the
evaluation of patients after dacryocystorhinostomy (DCR). METHODS: Computed
tomography scans of patients who underwent both successful and failed DCR were
examined to determine the relationship of the soft-tissue changes to the surgical
ostium, and the findings were correlated with postoperative results of office
probing and irrigation. RESULTS: After a successful DCR (n = 7), a patent
fistulous tract was confirmed by office probing and irrigation. A characteristic
"Y-on-its-side" configuration of the soft tissue was noted on a CT scan. Total
occlusion of the osteotomy by soft tissue on probing and irrigation corresponded
to a mucocelelike soft-tissue density with a central lucency and soft-tissue
obstruction (n = 2). Total occlusion of the osteotomy by inadequate excision of
bone and adjacent soft tissue, visualized by CT imaging, was confirmed by
palpation of bone by office probing (n = 1). Partial obstruction on probing and
irrigation was associated on a CT scan with an increased soft-tissue density (n =
4) and bone in the region of the osteotomy (n = 3). CONCLUSIONS: Computed
tomography allows visualization of a patent fistula after successful DCR as well
as soft-tissue or bone obstruction of the surgically created fistula after failed
DCR. When combined with probing and irrigation, CT helps to formulate a surgical
plan after failed DCR.
PMID- 10189640
TI - Direct orbital manometry in healthy patients.
AB - PURPOSE: To determine orbital tissue tension and orbital compartment compliance
in normal patients. METHODS: An orbital manometer was designed to directly
measure orbital tissue tension before, during, and after a 5-ml retrobulbar
injection of anesthetic in patients undergoing ocular surgery. Tissue tension was
recorded for 5 minutes after the injection. Orbital compliance was calculated as
change in volume divided by change in pressure. Data were collected from 18
normal orbits. RESULTS: Resting orbital tissue tension was 4.0 +/- 1.5 mmHg (mean
+/- standard deviation). After retrobulbar injection, orbital tissue tension rose
to 11.6 +/- 2.6 mmHg (p = 0.00000000009 compared with baseline). After 5 minutes,
tissue tension declined to 6.6 +/- 1.9 mmHg (p = 0.00000001 compared with
preinjection and p = 0.00002 compared with postinjection). Orbital compartment
compliance was 0.74 +/- 0.31 ml/mmHg. No adverse events occurred. CONCLUSIONS:
The authors' orbital manometer safely determined orbital tissue tension and
orbital compartment compliance in normal orbits. Retrobulbar injection causes
consistent measurable changes in orbital tissue tension. Directly assessing
orbital dynamics in vivo may prove useful both as an adjunct in the clinical
evaluation of patients with disorders resulting in an orbital compartment
syndrome as well as in assessing the risk of retrobulbar injection in orbits at
greater risk for complications from this procedure.
PMID- 10189641
TI - Pneumatocele of the orbit.
AB - PURPOSE: To describe an uncommon sinus condition that can cause proptosis.
METHODS: Intermittent unilateral proptosis and diplopia developed in a 29-year
old man. Computed tomography showed an enlarged frontal sinus with erosion of the
floor of the sinus and air in the orbit. RESULTS: Endoscopic ethmoidectomy and
frontal sinusotomy corrected an outlet check valve of the nasal frontal duct and
eliminated the proptosis. CONCLUSION: Pneumatocele of the orbit is an uncommon
cause of proptosis and diplopia and can be corrected with endoscopic sinus
surgery.
PMID- 10189642
TI - Low-dose radiotherapy for lymphoid lesions of the orbit and ocular adnexa.
AB - PURPOSE: There is no agreement within the radiation oncology and ophthalmic
communities regarding the treatment of lymphoid lesions of the orbit and ocular
adnexa. The authors report their experience with the use of low-dose radiation
therapy for malignant and benign lymphoid masses of the orbital region in a
series of 54 patients treated between 1985 and 1993. METHODS: All patients
received 2 Gy per day for a total of 24 Gy, except when the lesion was extensive,
in which case the therapy was 1.5 Gy per day for a total of 25.5 Gy. A diagnosis
was established by incisional surgical biopsy in 26 patients and aspiration
cytology in 28 patients. Those with a malignant or an indeterminate diagnosis
were evaluated with a modified Ann Arbor staging system. RESULTS: Low-dose
radiation therapy produced a complete response in 100% of the orbital lymphoid
lesions. This local control was maintained in 52 patients (96%) for the first
year and in 51 patients (95%) for 5 or more years with a mean follow-up of 7
years. One patient died of causes unrelated to the malignant lymphoma after the
first year of observation. The mean age of the 54 patients was 67 years, and the
range was 37 to 90 years. The mean ages of presentation for each location were:
orbit, 67 years; conjunctiva, 68 years; lacrimal gland, 66 years; and eyelids, 72
years. The female-to-male ratio was 1.25:1 (34 women and 20 men). In this series,
9 patients had benign processes, 38 patients had non-Hodgkin's lymphoma, and 7
patients had abnormalities of indeterminate cause. All histologic subtypes of non
Hodgkin's lymphoma involving the orbit responded equally well to therapy. Forty
five patients had clinically staged disease as follows: stage I, 21 patients;
stage II, 4 patients; stage III, 2 patients; and stage IV, 18 patients. Benign
disease, diagnosed in 9 patients, was not staged. CONCLUSION: Low-dose radiation
therapy proved effective in treating lymphoid lesions of the orbital area. No
treatment-limiting complications occurred. The only early side effects were mild
xerophthalmia and chemosis in 50% of patients, and the only chronic side effect
was mild xerophthalmia in 33% of patients. Cataracts, corneal ulcerations, and
retinal injury were not observed.
PMID- 10189643
TI - Desmoplastic spindle-cell melanoma of the eyelid with orbital invasion.
AB - PURPOSE: To describe the clinicopathologic features of a patient with a spindle
cell melanoma of the eyelid that exhibited orbital invasion. METHODS: Case
report. RESULTS: A slowly enlarging mass developed in the eyelid of a 50-year-old
woman. Excision of the mass showed desmoplastic spindle-cell melanoma. The tumor
recurred in the orbit, and an exenteration was performed. A second recurrence 7
months later was treated with radiation therapy. CONCLUSIONS: There is a
continuum of spindle-cell to desmoplastic melanoma. The prognosis of patients
with orbital invasion of melanoma is poor, and adjuvant treatment including
radiation and chemotherapy has little benefit.
PMID- 10189644
TI - Correction of eyelid anomalies in pachydermoperiostosis.
AB - PURPOSE: Pachydermoperiostosis, or primary hypertrophic osteoarthropathy, is a
rare disease, characterized by pachydermia, acropathy, and periostosis. The
authors propose the surgical correction of the eyelid anomalies in one stage.
METHODS: A 30-year-old patient with moderate blepharoptosis (3 mm) and increased
vertical and horizontal dimensions of the upper eyelids underwent fusiform
transverse excision of skin, orbicularis muscle, and tarsus; shortening of the
levator palpebrae superioris apeoneurosis by 13 mm; and 8-mm-wide wedge excision.
RESULTS: Histologic findings included hyperplasia of the tarso-conjunctival
plate, obstructive cystic dilatation of the sebaceous glands, extensive fibrosis,
and granulomatous reaction. Satisfactory functional and aesthetic results were
observed after surgery. CONCLUSION: Upper eyelid anomalies in
pachydermoperiostosis can be corrected in a single stage bilaterally with good
results.
PMID- 10189645
TI - Nodular fasciitis of the lower eyelid in a pediatric patient.
AB - PURPOSE: To describe a 14-year-old boy with a 1-month history of a rapidly
growing, nontender, lower eyelid mass. METHODS: The specimen was studied using
light microscopy. RESULTS: Although magnetic resonance imaging suggested a
chronic vascular lesion, histopathologic analysis after excisional biopsy was
consistent with nodular fasciitis. CONCLUSIONS: Nodular fasciitis is a relatively
common soft-tissue lesion and represents a benign, reactive process. Lesions in
the head and neck develop more frequently in children and adolescents than in
adults, but periorbital lesions are uncommon. This is the first reported case of
nodular fasciitis of the lower eyelid in a pediatric patient.
PMID- 10189646
TI - Comparison of three modified lidocaine solutions for use in eyelid anesthesia.
AB - PURPOSE: To compare pain on injection and the efficacy of anesthesia of three
modified lidocaine solutions for use in eyelid surgery: 1) 2% lidocaine with
1:100,000 epinephrine, 2) 2% lidocaine with 1:100,000 epinephrine buffered 9:1
with 8.4% sodium bicarbonate, and 3) 2% lidocaine with 1:100,000 epinephrine
diluted 1:9 with 0.9% bacteriostatic saline solution (with benzyl alcohol).
METHODS: In this prospective, randomized, double-masked, controlled clinical
trial, 30 consecutive patients undergoing bilateral identical eyelid surgery were
randomized to one of three treatment groups. Group 1 received buffered solution
on one side and stock solution on the other, group 2 received bacteriostatic
saline diluted solution on one side and stock solution on the other, and group 3
received buffered solution on one side and bacteriostatic saline diluted solution
on the other. Patients used a 5-point scale to rate the perceived pain on
injection and the pain felt during the operative procedure. RESULTS: Comparison
of mean injection pain scores showed that buffered solution was significantly
less painful than unmodified solution (2.2 versus 3.1, p < 0.05), bacteriostatic
saline modified solution was significantly less painful than unmodified solution
(0.9 versus 3.3, p < 0.05), bacteriostatic saline modified solution was
significantly less painful than buffered solution (1.2 versus 2.3, p < 0.05).
Comparison of mean intraoperative pain scores demonstrated no significant
difference between the solutions in any of the treatment groups. CONCLUSIONS: For
local anesthesia in eyelid surgery, bacteriostatic saline modified solution
provides more comfort on injection than either buffered or unmodified lidocaine
epinephrine solution and provides an adequate level of anesthesia that does not
differ significantly from either the buffered or unmodified solutions.
PMID- 10189647
TI - Is it time to question the routine use of anticholinergic agents in paediatric
anaesthesia?
PMID- 10189648
TI - Anaesthetic implications of thoracoscopic surgery in children.
AB - As the equipment and technique have improved, minimally invasive surgery is being
applied to younger and younger children. With the advent of this valuable
surgical technique, there are also specific modifications necessary in the
anaesthetic technique. When considering the anaesthetic implications of these
patients, one must account for both the patient's underlying status as well as
physiological derangements induced by the surgical procedure. The following
article attempts to address and review the specific anaesthetic implications of
thoracoscopic procedures in neonates, infants, and children including the
preoperative evaluation, intraoperative care and monitoring, and postoperative
issues including analgesia. The techniques of one-lung anaesthesia, commonly
required for thoracoscopy, are reviewed as well as consideration of the adverse
effects which can occur during thoracoscopy including inadvertent intravascular
CO2 embolism.
PMID- 10189649
TI - Position of the internal jugular vein in children. A study of the anatomy using
ultrasonography.
AB - The relative anatomy of the internal jugular vein (IJV) was studied in 25
patients undergoing cardiac catheterization under general anaesthesia, with the
use of a portable ultrasound probe. In 14 of cases the IJV was anterior, 1
anterolateral and in 10 lateral to the carotid artery between the two heads of
the sternocleidomastoid muscle. At the level of the cricoid cartilage, in six
cases the IJV was anterior, three anterolateral and in 16 of children the IJV was
lateral to the carotid artery. When attempting to cannulate the IJV, because of
the variability in relationship of the IJV to CA the technique used should be
modified depending upon the level at which cannulation is attempted. The position
of the IJV in the child appears to be so variable extra care should be taken when
cannulating the IJV and it should not be assumed that the techniques used in
adults are directly transferable.
PMID- 10189650
TI - Resistance to vecuronium in burned children.
AB - We compared the time-course of action of vecuronium in 16 burned children
undergoing excision and autograft surgery with that of ten unburned children.
Standardized anaesthesia was induced with thiopentone 4-6 mg kg-1 and fentanyl 1
microgram.kg-1 and maintained with endtidal 1-1.5% isoflurane in N2O/O2.
Neuromuscular responses were monitored by acceleromyography (TOF-Guard, Organon
Teknika/Biometer) with supramaximal train-of-four (TOF) stimuli delivered every
15s. Vecuronium 0.1 mg kg-1 was administered intravenously. Onset was recorded as
the time, in seconds, between the initial bolus of vecuronium and a decline in
the first twitch of TOF (T1) to 5% of control. The times for the recovery of T1
25%, 50% and 75% of control, recovery index and the recovery of TOF 25% and 50%
were recorded. Onset of action was found slower in burned patients (189 +/- 70 s)
than in control (98 +/- 20 s) (P < 0.01). Recovery times of T1(25), T1(50),
T1(75), TOF25 and TOF50 were significantly shorter in burned patients indicative
of decreased sensitivity to vecuronium (P < 0.01).
PMID- 10189651
TI - A new modification of anaesthesia mask for fibreoptic intubation in children.
AB - We made a paediatric anaesthesia mask suitable for fibreoptic intubation by
modifying a commercially available disposable mask with a ventilation port (Vent
port) on a side. We added a large fibreoptic port (FO port, 22 mm in ID) in the
middle of the mask to allow the passage of all sizes of paediatric tracheal
tubes. This FO port was covered with an elastic rubber membrane to allow air
tight fibrescopic manipulation Fibreoptic intubation was performed safely through
the FO port under continuous manual ventilation with anaesthetic gases via a Vent
port connected to the breathing circuit. We succeeded in tracheal intubation in
several infants and children with difficult airway in less than ten min, mainly
via the nasotracheal route. This fibreoptic mask provides a safer technique for
fibreoptic intubation in patients with difficult airways, especially in infants
and small children.
PMID- 10189652
TI - Jugular bulb temperature compared with non-invasive temperatures and cerebral
arteriovenous oxygen saturation differences during open heart surgery.
AB - Limited information is available about the correlation between cerebral
temperature and routine temperature measurements during cardiopulmonary bypass in
infants. Nasopharyngeal, tympanic membrane and rectal temperatures were compared
with jugular bulb temperature in ten infants operated on with moderate or deep
hypothermia. The cerebral arteriovenous saturation differences were correlated
with the temperatures at the four measurement sites. The jugular bulb and
nasopharyngeal temperatures showed the most rapid response during cooling and
rewarming. The tympanic temperature response varied in an unpredictable way.
Rectal temperature, which was the target for rewarming, lagged behind during both
cooling and rewarming. Overwarming at the end of cardiopulmonary bypass, seen as
jugular bulb and nasopharyngeal temperatures exceeding 38 degrees C, was common
after deep hypothermia. A high correlation was found between the cerebral
arteriovenous oxygen saturation differences and the jugular bulb temperature (r =
0.81) and the nasopharyngeal and the tympanic temperature (r = 0.79), whereas the
correlation with rectal temperature was weaker (0.66).
PMID- 10189653
TI - Can gastric intramucosal pH (pHi) predict outcome of paediatric cardiac surgery?
AB - In forty-two children undergoing cardiac surgery using hypothermic
cardiopulmonary bypass (CPB), a gastric tonometer was used intraoperatively to
estimate pHi, reflection of splanchnic perfusion. PHi monitoring was used to
predict early postoperative complications. Intramucosal acidosis appeared after
removal of the aortic clamp and remained after weaning of CPB. Fifteen children
(group C) developed early postoperative life-threatening complications. Twenty
seven children (group NC) had no major complications. Retrospective data analysis
showed a decrease of pHi during hypothermic CPB in the two groups but at
completion of surgery, pHi was significantly lower in the group C (7.13 +/- 0.04
vs 7.31 +/- 0.001, P < 0.001). Bypass and aortic clamp times were also longer in
group C and intraoperative core temperature lower. Continuous automated tonometer
gas analysis appeared more accurate for the monitoring of acute haemodynamic and
respiratory changes and should probably improve the predictive value of tonometry
in the future. Tonometry is highly sensitive and represents an interesting and
minimally invasive monitoring for critically ill children.
PMID- 10189654
TI - Comparison of morphine sulphate and codeine phosphate in children undergoing
adenotonsillectomy.
AB - We undertook a double-blind study to evaluate equianalgesic doses of
intramuscular morphine sulphate (0.15 mg.kg-1) and codeine phosphate (1.5 mg.kg
1) in 40 healthy children undergoing adenotonsillectomy. There were no
significant differences in pain scores, analgesic requirements or sedation scores
between the two groups over the following 24 h. More children vomited in the
morphine group (60%) than the codeine group (30%) between one and six h after the
procedure (P < 0.05). Codeine phosphate is associated with less postoperative
vomiting than morphine sulphate while providing comparable postoperative
analgesia for adenotonsillectomy.
PMID- 10189655
TI - Outcomes after single injection caudal epidural versus continuous infusion
epidural via caudal approach for postoperative analgesia in infants and children
undergoing patent ductus arteriosus ligation.
AB - Adequate postoperative analgesia enhances deep breathing and minimizes
respiratory complications after thoracotomy. This study compares postoperative
outcomes after single injection caudal epidural vs continuous infusion epidural
via caudal approach for postoperative analgesia in infants and children
undergoing thoracotomy for patent ductus arteriosus (PDA) ligation. A
retrospective chart review was performed for 27 children who had undergone PDA
ligation. The children were divided into three groups. We compared patient
demographics, surgical duration, anaesthesia duration, length of ICU stay,
incidence of emesis requiring treatment, time required to establish regular oral
intake, requirement for supplemental intravenous opioids during the first
postoperative day, and length of hospital stay. For paediatric patients
undergoing PDA ligation, postoperative analgesia with continuous infusion
epidural via caudal approach produced shorter ICU stay, less occurrence of
postoperative emesis, earlier oral intake, elimination of intravenous opioid
supplementation, and shorter hospital stay compared with single injection caudal
epidural techniques.
PMID- 10189656
TI - Observation of the correlation of postanaesthesia recovery scores with early
postoperative hypoxaemia in children.
AB - To observe the correlation of the postanaesthesia recovery score (PARS) with the
incidence, and severity of early postoperative hypoxaemia in children, 1213
infants and children, ASA physical status I, aged three months to 14 years,
scheduled for elective plastic surgery were included in this study. Arterial
oxygen saturation (Spo2) levels were recorded while children were breathing room
air shortly after arrival in the recovery room (0 min), and 5, 10, 15, 20, 30,
40, 50, 60, 120 and 180 min thereafter. The PARS was also determined on all
patients when Spo2 levels were recorded in the recovery room. On the basis of
different PARS, children were divided into the three groups: Group 1-children
having the PARS of < or = 6; Group 2-children having the PARS of 7-9; and Group 3
children having a PARS of 10. The results showed that during the early
postoperative period, the incidence and severity of hypoxaemia correlated closely
with the PARS. The lower the children's PARS, the higher the incidences of
hypoxaemia (Spo2 = 86-90%) and severe hypoxaemia (Spo2 < or = 85%). The
incidences of hypoxaemia and severe hypoxaemia were 12.9% and 15.8%,
respectively, in Group 1, 20.9% and 2.9% in Group 2, 0.8% and 0% in Group 3.
There were significant differences among the three groups. Of the 91 children who
required O2 supplementation in the recovery room because of low measured Spo2, 69
had the PARS of < or = 6, and 22 had the PARS of 7-8. It is concluded that if a
patient has a PARS of 10, the patient will not need routine oxygen supplement
because hypoxaemia will not occur.
PMID- 10189657
TI - Failure of the laryngeal mask to secure the airway in a patient with Hunter's
syndrome (mucopolysaccharidosis type II).
AB - We present a case-study of a boy with Hunter's syndrome (mucopolysaccharidosis
type II) and stridor in which a laryngeal mask airway (LMA) failed to secure
airway control. A rigid bronchoscopy was performed and a polypoid formation
discovered. We believe that the use of the LMA could explain the laryngeal
obstruction in this child.
PMID- 10189658
TI - Preoperative hypoglycaemia, propranolol and the Jervell and Lange-Nielsen
syndrome.
AB - The Jervell and Lange-Nielsen syndrome is an autosomal recessive trait
characterized by deafness and electrocardiographic changes. These changes include
prolongation of the QT interval and T-wave inversion. Treatment may include the
use of beta-blockers to prevent the development of malignant ventricular
arrhythmias and sudden death. We report a patient with this syndrome, who was
receiving propranolol orally and who became hypoglycaemic during the preoperative
fasting period prior to cochlear implantation.
PMID- 10189659
TI - Skin conductance responses in paediatric Harlequin syndrome.
AB - We report a novel and simple application of skin conductance response (SCR)
testing for diagnosis of a new-onset iatrogenic Harlequin syndrome in an infant.
Isolated ipsilateral facial pallor, complicated by thermally induced systemic
sympathetic vasodilatation, and preferential lateral decubitus positioning,
mimics harlequin colour change. Correct diagnosis as Harlequin syndrome with
facial sympathetic interruption was demonstrated by diminution of SCR.
PMID- 10189660
TI - Management of difficult airways with a laryngeal mask airway under propofol
anaesthesia.
AB - We report four cases of difficult airway managed with a laryngeal mask airway
(LMA) under propofol anaesthesia; this method was chosen to minimize
psychological and physical trauma. Case 1 was a boy with dermatomyositis; Case 2,
a girl wearing a base ring of a stereotactic frame; Case 3, a boy with Treacher
Collins syndrome; Case 4, a boy with Goldenhar syndrome. They were anaesthesized
with propofol and though spontaneous ventilation became shallower, or apnoea
occurred, the stimulus of inserting an LMA awakened the patient and caused more
active spontaneous ventilation while a patent airway was established by the LMA.
All tracheal intubations were performed smoothly and without delay through the
LMA, and we believe that psychological and physical trauma was thus minimized.
PMID- 10189661
TI - Pulmonary artery catheter placement under transoesophageal echocardiography
guidance.
AB - Despite correct positioning pulmonary artery catheters may be displaced
accidentally. Repositioning may prove to be difficult, especially when high
pulmonary artery pressures are present. After failure of usual placement methods,
transoesophageal echocardiography was used to guide repositioning of a displaced
Swan-Ganz catheter in the early postoperative course after cardiac surgery in a
child. This technique proved to be useful in visualizing intracardiac catheter
orientation and facilitating pulmonary artery catheter placement at bedside,
avoiding transportation of a haemodynamically unstable patient.
PMID- 10189662
TI - The management of extreme hypernatraemia secondary to salt poisoning in an
infant.
AB - We describe a five-week-old boy who had seizures and extreme hypernatraemia
secondary to ingesting an improper home-made formula. Initial sodium
concentration was 211 mmol.l-1. Other clinical and biological features were
moderate dehydration and renal insufficiency with generous urine output and high
urinary sodium concentration. Fluid therapy with hypotonic dextrose solution
corrected the volume deficit in 48 h and progressively decreased the serum sodium
concentration. During ICU stay the patient developed recurrent episodes of
seizures and pulmonary oedema requiring mechanical ventilation for five days.
Recovery was complete with no abnormal sequelae after a ten-month follow-up. Salt
poisoning is in unusual cause of extreme hypernatraemia. It can be safely managed
with fluid therapy alone if urine output is preserved, with progressive decrease
of serum sodium as target. If this condition is recognized, outcome should be
favourable.
PMID- 10189663
TI - Electrocardiographic inscription of diaphragmatic contractions during
anaesthesia.
AB - An electrocardiographic artifact was noted on a child under general anaesthesia.
The artifact was caused by rhythmic diaphragmatic contractions. A systematic
approach to distinguish an artifact from a cardiac electrophysiological event is
presented.
PMID- 10189664
TI - Preoxygenation in infants and children.
PMID- 10189665
TI - Airway rescue and drug delivery in an 800 g neonate with the laryngeal mask
airway.
PMID- 10189666
TI - Persistent atrial fibrillation following central venous cannulation.
PMID- 10189667
TI - [HIV post-exposure prophylaxis after sexual risk contact].
PMID- 10189668
TI - [Post-exposure HIV prevention: eligibility of patients recently infected by
sexual exposure].
AB - QUESTION: Post-exposure prophylaxis (PEP) is effective in preventing HIV
infection after professional exposure. PEP is also recommended after inadvertent
sexual exposure if two conditions are met: the source person is known to be HIV
infected, and exposure to this person occurred only once or is accidental. The
objective of this study is to describe the circumstances of sexual exposure and
determine how frequently these conditions were present among patients diagnosed
during primary HIV infection. METHODS: Physicians of 35 patients diagnosed with
primary HIV infection provided detailed information on the circumstances of
infection as well as on the patients and source persons. RESULTS: Most patients
were homosexual (71%), and 91% were male. Only one patient (3%) had a single
exposure with a known HIV-infected person and was therefore eligible for PEP.
Eight patients (23%) who did not know the HIV status of their partner would have
been eligible considering single exposure as a sufficient criterion for PEP. Oro
genital contact appears to account for transmission in four instances. Eleven
persons (31%) were infected after sexual contact with their stable partner, of
whom 7 did not known his/her HIV status. Twelve patients (34%) were infected
after multiple unprotected sexual contact with unknown partners. CONCLUSION: The
direct impact of PEP in terms of HIV infections prevented is likely to be small.
PEP will not make up for the failure of other prevention methods. It may,
however, contribute to the disclosure and the discussion of risk situations and
help physicians provide individual counselling taking into account the precise
context of risk behavior.
PMID- 10189669
TI - [Early diagnosis of primary HIV infections: using a combined screening test (p24
antigen and anti-HIV antibodies)].
AB - Laboratory diagnosis of HIV infection is based on the detection of HIV
antibodies. There is a delay between infection and seroconversion (i.e. the
appearance of specific HIV antibodies) corresponding to a window period which may
last several weeks. Reduction of the length of the window period might be
achieved by using p24 antigen and/or viral nucleic acid detection assays. We have
evaluated a new screening assay (VIDAS HIV DUO) designed for the concurrent
detection of HIV antibodies and p24 antigen, using sequential samples of 34 HIV-1
seroconverting patients and 236 HIV-positive samples confirmed by Western blot.
Results were compared with those obtained with two third-generation anti-HIV
antibody screening assays. The 236 confirmed HIV-positive samples including 3 HIV
1 subtype O and 2 HIV-2 samples were found to be positive by the 3 assays. All
128 sequential samples from 34 seroconverting patients were found to be positive
using the DUO assay, including 20/20 pre-seroconversion samples (p24 antigen
positive and anti-HIV negative). The new screening assay was positive before a
third-generation anti-HIV screening assay gave positive results in 14/34 patients
(41%). Using the DUO assay, the mean reduction of the window period was 4 days.
PMID- 10189670
TI - [Swiss study of chemotherapy of alveolar echinococcosis--review of a 20-year
clinical research project].
AB - Alveolar echinococcosis (A. E.), caused by Echinococcus multilocularis, behaves
biologically like a malignant tumour of the liver which is best treated by
radical surgery. However, radical surgery can be performed only in about 20-30%
of A. E. cases. The efficacy of chemotherapy with benzimidazole derivatives for
inoperable cases is debated. The results of a prospective Swiss chemotherapy
trial, which started in 1976, are reviewed. In the last 20 years a total of 110
patients has been included in our protocol and 74 of these patients had
inoperable or palliatively operated A. E. (average observation time 12.8 years).
The efficacy of long-term chemotherapy was documented by increase of 10-year
survival compared to historical (untreated) A. E. cases (80 vs 6%) and by
reduction or stabilisation of the liver lesions in 83% of cases during long-term
chemotherapy. Several relevant problems remain to be clarified, e.g. optimal
duration of chemotherapy, the controversy as to whether chemotherapy is
parasitostatic or parasitocidal, the establishment of reliable routine methods
for short-term assessment of therapeutic efficacy, and comparative studies
between mebendazole and albendazole. Furthermore, additional studies are
necessary in collaboration with basic science, for example on the impact of the
increasing fox population, with invasion of large agglomerations, on infection
risk in the Swiss population, and the importance of individual immune competence
for susceptibility or resistance to A. E.
PMID- 10189671
TI - [Onychogryphosis].
PMID- 10189672
TI - Medical-ethical guidelines on the definition and determination of death with a
view to organ transplantations. Swiss Academy of Medical Sciences (SAMS).
PMID- 10189673
TI - Effects of preslaughter handling on the behaviour, blood biochemistry and
carcases of farmed red deer.
AB - Eight groups of six red deer (four groups of males and four groups of females)
were held overnight in an unfamiliar paddock, after which they were moved into a
holding pen and slaughtered sequentially by stunning with a captive bolt pistol
in a restraining pen. On entering the restraining pen, half the deer in each
group were stunned immediately, but the other half were stunned after 10 minutes.
Deer spent much of the initial period in the holding pen standing stationary in
'alert' postures, but became less alert over time. A significantly higher
proportion of males than females were observed in alert 'head-up' postures in the
restraining pen. Deer held in the restraining pen for 10 minutes had
significantly higher plasma cortisol concentrations than those which were stunned
immediately. Females had a significantly higher glycogen concentration postmortem
in both the liver and semimembranosus muscle than males, and deer held in the
restraining pen for 10 minutes had a significantly lower liver glycogen
concentration than deer which were slaughtered immediately. Males had
significantly higher semimembranosus muscle pHu values than females, although the
differences were small, and of the 14 deer with pHu values above 6-0, 11 were
males.
PMID- 10189674
TI - Effects of temperature on the survival of Tritrichomonas foetus in transport,
Diamond's and InPouch TF media.
AB - The abilities of two isolates of Tritrichomonas foetus to survive and replicate
in transport and Diamond's medium or in the InPouch TF system (Bio-Med
Diagnostics) when exposed to different temperatures for different periods were
determined in a series of experiments. Tubes containing thioglycollate transport
medium or pouches were inoculated with 4000 to 5000 organisms and kept for up to
seven days at 37 degrees C, 22 degrees C, 4 degrees C, or -20 degrees C. When the
holding time had elapsed, the numbers of motile T foetus were counted. Samples in
transport medium were transferred to Diamond's medium, and both the pouches and
tubes containing Diamond's medium were incubated at 37 degrees C. The cultures
were examined and counted four or five times during the 10 to 14 day culture
period. The sensitivity of the test under the different conditions, expressed as
the number of positive cultures/the total number of samples x 100, varied from
zero to 100 per cent depending upon the combination of variables considered. In
each medium, with both isolates of T foetus, all samples kept for up to four days
at 22 degrees C or 37 degrees C were positive. All cultures of samples kept more
than five days at 4 degrees C were negative. No positive cultures were detected
when samples were kept more than three hours at -20 degrees C. The day on which
the cultures reached mean peak concentration varied with the temperature at which
the samples had been kept before they were cultured.
PMID- 10189675
TI - Analysis of scintigraphical lung images before and after treatment of horses
suffering from chronic pulmonary disease.
AB - Scintigraphical analysis of the ratio of inhalation (I) to perfusion (Q) was
designed to determine whether chronic pulmonary disease in horses induced
mismatches in I/Q and to assess whether medical treatment would restore an I/Q
distribution pattern identical to that of control horses. In addition, the
results of the I/Q analysis were correlated with the alveolar-arterial PO2
difference (AaDO2). The I/Q matching found in a group of control horses was
compared with the I/Q analysis of a group of diseased horses before and after
their clinical signs had been treated. The analysis indicated that there was
mismatching between I and Q before they were treated. The treatment improved the
diseased horses, pulmonary function but there was still heterogeneity in the I/Q
distribution after they had been treated. The I/Q analysis parameters were well
correlated with the ratio of ventilation (VA) and pulmonary blood flow (Q),
evaluated by the determination of AaDO2.
PMID- 10189676
TI - Influence of gonadotrophin supplementation on the in vitro maturation of bitch
oocytes.
PMID- 10189677
TI - Detection of Brucella species DNA in the stomach content of aborted sheep fetuses
by PCR.
PMID- 10189678
TI - Chewing lice, sheep scab and systemic endectocides.
PMID- 10189679
TI - Health of dogs purchased from animal rescue centres.
PMID- 10189680
TI - [Therapies in HIV infection].
PMID- 10189681
TI - [Antiretroviral therapy 1998/1999: what is our current status?--Avoiding therapy
failure instead of expecting it].
AB - The stunning clinical benefit of antiretroviral therapy is associated with long
term viral suppression. Treatment failure has therefore been defined as
incomplete suppression of viral replication, however, in clinical practice
success is also seen in a substantial proportion of patients with ongoing viral
replication, a phenomenon which is not understood at this time. The main reason
for treatment failure is the development of resistance due to the inability of
many patients to comply with the daunting challenge of the complex antiretroviral
therapy. An "era of compliance" is now necessary to sustain and expand the
benefits of these therapies.
PMID- 10189682
TI - [Guidelines for implementing antiretroviral therapy].
AB - The rapid evolution of new information has introduced extraordinary complexity
into the treatment of HIV-infected persons. Therefore it is recommended that care
should be supervised by an expert. With regard to specific recommendations,
treatment should be offered to all patients with the acute HIV syndrome and all
patients with symptoms ascribed to HIV infection. The strength of the
recommendation to treat asymptomatic patients should be based on the patient's
willingness to accept therapy, the probability of adherence with the prescribed
regimen, and the prognosis in term of time to an AIDS-defining disease as
predicted by plasma HIV RNA levels and CD4+ T-cell counts. Once the decision has
been made to initiate antiretroviral therapy, the goal is maximum viral
suppression for as long as possible. Results of therapy are evaluated primarily
with plasma HIV RNA levels: these are expected to show a one-log (10-fold)
decrease at 8 weeks and no detectable virus at 4 to 6 months after initiation of
treatment. Failure of therapy may be ascribed to nonadherence, inadequate potency
of drugs or suboptimal levels of antiretroviral agents, resistance, and other
factors that are poorly understood. Patient education and involvement in
therapeutic decisions is important for all medical conditions but is considered
especially critical for HIV-infection and its treatment.
PMID- 10189683
TI - [Antiretroviral therapy in children].
AB - Former antiretroviral treatment strategies in pediatric HIV-infection were based
on the occurrence of clinical symptoms or loss of CD4-cells. Because of toxicity
and dosing concerns HIV-infected children have often been denied new drugs
routinely prescribed to HIV-infected adults. Over the last few years new insights
into the pathogenesis of HIV disease, the availability of quantitative viral load
measurements and the development of new antiretroviral agents have brought
dramatic changes in our understanding of the disease and the role of
antiretroviral treatment. Similar to adults it was also shown in children that
potent combination regimens applied early in the course of HIV-infection can
achieve long-term control of viral replication and thus preservation of immune
function and reduction of disease progression. However, there are only poor
clinical data regarding dosing, pharmacokinetics, and antiretroviral activity of
new combination therapies in infants and young children, pediatric studies are
urgently needed. Consensus has been growing that children must not be denied
modern therapy because of the lack of pediatric clinical data, and recently
treatment guidelines were developed by specialists in pediatric HIV-care which
recommend early combination antiretroviral therapies in infants and young
children. It is likely that recommendations will change as more data become
available about the effects of different treatment regimens.
PMID- 10189684
TI - [Post-exposure prevention of HIV infection].
AB - The risk of health-care workers to become infected with HIV during professional
activities is low. Prevention of exposures by obeying appropriate precautions is
the most important means to lower this risk further. During the last few years it
has become more and more likely that an immediate antiretroviral postexposure
prophylaxis can prevent at least 80% of possible infections. Thus, each exposure
to HIV-positive blood should be considered an acute medical emergency. Immediate
counseling by qualified experts and possibilities to start postexposure
prophylaxis as soon as possible should be available in all medical settings.
PMID- 10189685
TI - [Reducing perinatal transmission by antiretroviral therapy].
AB - In 1994 the results of Pediatric AIDS Trials Group (PACTG) Protocol 076
documented that AZT chemoprophylaxis could reduce perinatal HIV-transmission by
67%. Epidemiologic data have since confirmed the efficacy of AZT for reduction of
perinatal transmission and have extended this efficacy to children of women with
advanced disease, low CD4 cell count and prior AZT therapy. Additionally
substantial advances have been made in the understanding of the pathogenesis of
the HIV-infection, and in the treatment and monitoring of HIV-disease. These
advances have resulted in changes in standard antiretroviral therapy for HIV
infected adults as well as in children and pregnant women. Antiretroviral therapy
in pregnancy has two goals: optimizing therapy for the mother and prevention of
perinatal transmission. It has to be taken into account that there are only a few
data on short and long term effects on the fetus and newborn.
PMID- 10189686
TI - Resistance--clinical significance and diagnostics.
AB - One of the most important factors, inhibiting the success of antiretroviral
treatment of HIV infections is the development of drug resistant HIV strains in
the patients during therapy. Detection and identification of such resistant virus
strains is therefore becoming increasingly important for the clinical management
of the patients, as well as for the detection of the transmission of already
resistant virus strains. In the following paper different methods for the
genotypic and phenotypic screening for resistant HIV-strains are compared and the
problems of resistance testing are discussed.
PMID- 10189687
TI - [Immunotherapy of HIV infection].
AB - Despite of suppression of HIV-viremia antiretroviral therapy is not able to
achieve a complete reconstitution of the immune system in advanced HIV-1-infected
patients. In addition, drug therapy can be limited over time by side effects and
emergence of drug resistance. This has evoked growing interest in developing
immune based therapies of HIV-1 infection. Current strategies for immune
reconstitution are focusing on cytokines such as interleukin-2 (IL-2) and "Colony
stimulating factors" (CSF). Combinations of IL-2 with antiretroviral drug
combinations can induce a significant increase of CD4-counts. However, it has not
been proven yet, that IL-2 can restore functional immunocompetence and that it
can influence the clinical course of HIV-1-infection. Polyvalent immunoglobulins
have been successfully used for the treatment of recurrent bacterial infections.
Colony stimulating factors (CSF) can improve neutropenia in HIV-1-infection and
there is growing evidence that CSF are useful in the treatment of bacterial
infections in patients even with normal leucocyte counts. A variety of different
therapeutic vaccines are currently tested in clinical trials. These vaccines
could enhance HIV-1-specific immunological effector mechanisms, but so far they
had no effect on HIV-1-viremia or on the course of disease. Further studies are
necessary to test whether new vaccination strategies in combination with potent
antiretroviral drug therapies can contribute to a better long-term control of HIV
1.
PMID- 10189688
TI - [Antiretroviral drugs 1998/1999].
AB - Combination antiretroviral therapy has proven to be the most effective approach
to treat HIV disease. The primary goal of treatment for HIV infection is to
achieve maximal and durable suppression of viral replication. After decrease of
viral load numerical and functional recovery of the immune system is observed and
has been associated with better clinical performance of patients. The number of
antiretroviral drugs has increased over the last years and currently 12 compounds
are available. Wise combinatorial use of these drugs, extensive information and
long-term motivation of patients, regular and correct intake are a prerequisition
rather than a guarantee of therapy success. These drugs exhibit several class-
and substance-specific short-/long-term toxicities, complex pattern of cross
resistance and drug-drug interactions and therefore in depth knowledge of the
pharmacology of antiretroviral drugs is mandatory for primary care providers.
PMID- 10189689
TI - Electrokinetic injection in capillary electrophoresis and its application to the
analysis of inorganic compounds.
AB - In capillary electrophoresis, electrokinetic injection is a highly controversial
sampling technique. It is a simple mode of sample introduction which is suitable
for on-line preconcentration of the analytes, but its precision and accuracy are
more strongly affected by experimental conditions compared to hydrodynamic
injection. In the first part of this paper the features of electrokinetic and
hydrodynamic injections are compared, followed by a detailed discussion on the
different biases of electrokinetic injection and on how to reduce them. Finally,
applications of the electrokinetic injection are reviewed with special emphasis
on the analysis of inorganic compounds.
PMID- 10189690
TI - Chemical modification of analytes in speciation analysis by capillary
electrophoresis, liquid chromatography and gas chromatography.
AB - Chemical modification of target analytes is widely used in modern analytical
methods. This review focuses on the application of chemical modification
techniques is the simultaneous analysis of metallic species by capillary
electrophoresis, liquid chromatography and gas chromatography. Emphasis is placed
on the procedures relating to analyses carried out by capillary electrophoresis.
The development of this topic in the past five years is evaluated for liquid
chromatography and gas chromatography. The advantages, performance and
application in real samples are compared for the three techniques.
PMID- 10189691
TI - Capillary electrophoresis of inorganic anions.
AB - This review deals with the separation mechanisms applied to the separation of
inorganic anions by capillary electrophoresis (CE) techniques. It covers various
CE techniques that are suitable for the separation and/or determination of
inorganic anions in various matrices, including capillary zone electrophoresis,
micellar electrokinetic chromatography, electrochromatography and capillary
isotachophoresis. Detection and sample preparation techniques used in CE
separations are also reviewed. An extensive part of this review deals with
applications of CE techniques in various fields (environmental, food and plant
materials, biological and biomedical, technical materials and industrial
processes). Attention is paid to speciations of anions of arsenic, selenium,
chromium, phosphorus, sulfur and halogen elements by CE.
PMID- 10189692
TI - Determination of platinum (II,IV) and palladium(II) as thiocyanate complexes by
capillary zone electrophoresis analysis of carboplatin and similar drugs.
AB - The thiocyanate complexes of Pd(II), Pt(II) and Pt(IV) were studied by capillary
zone electrophoresis. Pd(II) can be detected in the form of the thiocyanate
complex at 305 nm with higher sensitivity than in the form of its chloro complex
(absorption maximum 214 nm). A detection limit equal to 5 ppb for Pd has been
finally achieved. The possibility of simultaneous determination of Pd(II) and
Pt(IV) in the form of thiocyanate complexes has also been demonstrated. When the
method optimized for the determination of Pt(II) was applied to the drugs
Cykloplatin and Ribocarbo (containing carboplatin) and Platidiam (containing
cisplatin), good agreement of the platinum content with the declared value was
obtained. Samples of vehicle exhaust particulates (National Institute for
Environmental Studies, Japan, No. 8 reference material) were also analyzed.
PMID- 10189693
TI - Antimony speciation in environmental samples by interfacing capillary
electrophoresis on-line to an inductively coupled plasma mass spectrometer.
AB - Antimony is a widely distributed trace element of ecotoxicological interest. A
pathway via bioalkylation of inorganic Sb species is discussed in the literature,
resulting in organically bound Sb species. Therefore, Sb speciation becomes
increasingly a matter of interest for risk assessment in the environment. This
contribution investigates the possibilities of CE on-line hyphenated to ICP-MS
for Sb speciation. Two methods are employed, both highly resolving the species
but only one preserving the species stability. The latter used Na2HPO4/NaH2PO4,
20 mM, pH 5.6 as the background electrolyte and NaOH or acetic acid as stacking
electrolyte 1 or stacking electrolyte 2, respectively. Detection limits of 0.1
microgram/1-0.7 microgram/1, depending on species, were achieved. When analysing
liquid phases from fouling and sewage sludge up to eight antimony species were
detected. Sb (V) as well as methylated Sb species were found.
PMID- 10189694
TI - Application of capillary electrophoresis to the analysis of inorganic ions in
environmental samples.
AB - A comprehensive review is presented of the state-of-the-art of capillary
electrophoresis for application to the analysis of inorganic species, mainly
ions, in environmental samples. This brief review covers the developments
principally in sensitivity and matrix interference for the determination of
inorganic ions in the following samples: drinking, mineral, surface, and ground
waters, rainwater, snow, seawater, brine and waste waters, aerosol, and others.
References published mainly from 1995 to 1997 were summarized in this review.
PMID- 10189695
TI - Analysis of inorganic species in environmental samples by capillary
electrophoresis.
AB - The use of capillary electrophoresis for the determination of inorganic species
in environmental samples is reviewed. Topics covered include the separation of
inorganic anions, inorganic cations, transition metal cations and organometals in
different environmental matrices, such as atmospheric deposition, atmospheric
aerosols, gases, natural waters, waste waters, soil, sediment and marine
biological samples. Cited literature is gathered according to the type of matrix,
so that the focus is on the discussion of matrix effects rather than on the
method development for a single class of compounds. For each matrix, surveyed
methods are tabulated in order to assist the method selection. Innovative
applications of capillary electrophoresis to advanced environmental research are
also emphasised.
PMID- 10189696
TI - Determination of inorganic ions in food and beverages by capillary
electrophoresis.
AB - A review of the applications of electrophoresis to the determination of inorganic
anions (sulphate, sulphite, phosphate, nitrate, nitrite and halides) and
inorganic cations (ammonium, alkali and alkaline metals and trace elements) in
food and beverages is presented.
PMID- 10189697
TI - Application of capillary isotachophoresis and capillary zone electrophoresis to
the determination of inorganic ions in food and feed samples.
AB - The purpose of this review is to summarise critically the possibilities of
capillary isotachophoresis and capillary zone electrophoresis for the
determination of inorganic ions in food and feed samples. This article covers
papers published since 1977.
PMID- 10189698
TI - Phosphate as a limiting factor for the cell division of tobacco BY-2 cells.
AB - The re-addition of phosphate to tobacco BY-2 cells deprived of phosphate for 3 d
induced cells to semi-synchronously re-enter the cell cycle from a static state.
Though the addition of auxin to auxin-starved tobacco BY-2 cells also induced
cell division (Ishida et al. 1993), some major differences were observed between
these two systems. BY-2 cells lost the ability to re-enter the cell cycle after
prolonged periods of auxin deprivation, but in contrast retained this ability
after longer periods in the absence of phosphate. By differential cDNA screening
we identified a phosphate-induced gene phi-1. phi-1 was rapidly induced by the
addition of phosphate with transcript levels starting to decrease by the start of
DNA synthesis. phi-1 does not share any significant homology with any gene with
known functions over its full length. However, the N-terminus shared some
homology with plasma membrane ATPases suggesting that it may be involved in some
process of phosphorylation. Immunolocalization of the phi-1 gene product revealed
that it rapidly accumulated in the cytoplasm prior to the start of plastid and
nuclear DNA synthesis. These results are discussed in relation to the role of
phosphate in inducing plant cell division.
PMID- 10189699
TI - Targeted inactivation of the gene psaK encoding a subunit of photosystem I from
the cyanobacterium Synechocystis sp. PCC 6803.
AB - Mutant strains of the unicellular cyanobacterium Synechocystis sp. PCC 6803, in
which the psaK gene was insertionally inactivated by targeted mutagenesis, were
constructed. The gene is one of the two potential PsaK-coding genes which have
been found as a result of the genome project with this cyanobacterium. One of the
mutants was characterized in detail. A monocistronic, 480-nucleotide mRNA of psaK
was absent in total RNA from the mutant cells. Inactivation of psaK had little
effect on the accumulation of polypeptides in the isolated PSI complexes except
for a polypeptide with an apparent molecular mass of 4.6 kDa which was absent in
the mutant. The amino-terminal amino acid sequence of the 4.6-kDa polypeptide
confirmed that it was the translation product of psaK and further revealed a
presequence of PsaK. Characteristics of photoautotrophic growth at different
temperatures, the amount of chlorophyll per cell, photosynthetic electron
transport rates with rates with various electron acceptors, the kinetics of
charge recombination between P700+ and reduced FA/FB, and the molar ratio of
chlorophyll to P700, of the mutant were not significantly different from those of
the wild type. Furthermore, the trimer to monomer ratio of the PSI complexes
isolated from the mutant was similar to that isolated from the wild type.
PMID- 10189702
TI - Characterization of cytosolic cyclophilin from guard cells of Vicia faba L.
AB - The effect of immunosuppressant cyclosporin A (CsA) on inward-rectifying K(+)
channels and biochemical analysis have indicated the presence of cyclophilin in
guard cells of Vicia faba. In this study, we identified a full-length cDNA
sequence, vcCyP, encoding cyclophilin (CyP), a peptidyl-prolyl cis-trans
isomerase of guard cell protoplasts (GCPs) from Vicia faba L. The deduced amino
acid sequence revealed that vcCyP contained 171 amino acid residues and exhibited
a strong similarity to previously described cytosolic CyP isoforms from other
plants. vcCyP had seven extra amino acid residues, which is a characteristic of
the cytosolic form of plant CyPs. A complex of recombinant vcCyP and CsA
inhibited the phosphatase activity of bovine calcineurin, a type 2B protein
phosphatase, with a half-inhibitory concentration of 0.2 microM. Protein
phosphatase activity was measured in the cytosolic fraction of GCPs using a 32P
labeled myelin basic protein (32P-MBP) and the activity was increased by a
physiological concentration of Ca2+ (1 microM). This Ca(2+)-stimulated
phosphatase activity was inhibited by CsA, suggesting the presence of both
cytosolic CyP and calcineurin-like protein phosphatase in guard cells. Northern
blot analysis showed that the transcription level of vcCyP was much higher in
GCPs than in root and leaf tissues of Vicia.
PMID- 10189703
TI - Semi-automatic laser beam microdissection of the Y chromosome and analysis of Y
chromosome DNA in a dioecious plant, Silene latifolia.
AB - Silene latifolia has heteromorphic sex chromosomes, the X and Y chromosomes. The
Y chromosome, which is thought to carry the male determining gene, was isolated
by UV laser microdissection and amplified by degenerate oligonucleotide-primed
PCR. In situ chromosome suppression of the amplified Y chromosome DNA in the
presence of female genomic DNA as a competitor showed that the microdissected Y
chromosome DNA did not specifically hybridize to the Y chromosome, but hybridized
to all chromosomes. This result suggests that the Y chromosome does not contain Y
chromosome-enriched repetitive sequences. A repetitive sequence in the
microdissected Y chromosome, RMY1, was isolated while screening repetitive
sequences in the amplified Y chromosome. Part of the nucleotide sequence shared a
similarity to that of X-43.1, which was isolated from microdissected X
chromosomes. Since fluorescence in situ hybridization analysis with RMY1
demonstrated that RMY1 was localized at the ends of the chromosome, RMY1 may be a
subtelomeric repetitive sequence. Regarding the sex chromosomes, RMY1 was
detected at both ends of the X chromosome and at one end near the pseudoautosomal
region of the Y chromosome. The different localization of RMY1 on the sex
chromosomes provides a clue to the problem of how the sex chromosomes arose from
autosomes.
PMID- 10189704
TI - Cell-specific expression of genes of the lipid transfer protein family from
Arabidopsis thaliana.
AB - We have characterized three cDNAs from a gene family encoding lipid transfer
proteins, LTP, from Arabidopsis thaliana (Wassilewskija). In addition to the
already characterized Ltp1, our analysis includes Ltp2 and Ltp3, two sequences
previously known as expressed sequence tags (EST) only. The deduced amino acid
sequences of the three cDNAs share 56 to 57% identity and show unique tissue- and
cell-specific expression. Genes Ltp1 and LTp2 are located within approximately
1.4 kb of each other in tandem orientation. RNA hydridizations showed that all
three LTP are expressed in flowering meristems, flowers and developing seeds.
Ltp1 is expressed in leaves in addition. Ltp3, though not Ltp2, is also expressed
in a short segment of the stem close to the flowering meristem. In contrast to
the epidermis-specific Ltp1, both Ltp2 and Ltp3 are not restricted to the
epidermis, but are also expressed in sub-epidermal layers of the organs in which
they are found. In the upper stem segment, Ltp3 is predominantly cortical. It
appears that the expression of these three cDNAs is sufficient to account for the
formation of LTP in all meristematic and expanding cells of the aboveground
plant. Evolutionary analysis allows the conclusion that each Ltp belongs to a
different sub-family of genes. Additionally, parsimony analysis provides evidence
that several copies of Ltp genes already existed in ancestors of the Brassicaceae
family.
PMID- 10189705
TI - Expression of a gene for cyclophilin which contains an amino-terminal endoplasmic
reticulum-targeting signal.
AB - We isolated a novel gene for cyclophilin (CyP) first identified as an
intracellular target of the immunosuppressant cyclosporin A and also known to
have peptidyl-prolyl cis-trans isomerase (PPIase) activity, named ATCYP5 from
Arabidopsis thaliana. ATCYP5 encoded a polypeptide with 201 amino acids with a
putative ER-targeting signal sequence at its N-terminal, but without the typical
ER-retention signal in its C-terminal. In addition, ATCYP5 protein contained a
seven amino-acid long sequence which has been found previously only in cytosolic
CyPs from plants. The synthetic mutant green fluorescent protein (sGFP; S65T) was
fused to the N-terminal part of ATCYP5, and expressed in tobacco BY-2 cells. The
fluorescence derived from the fusion protein was detected mainly around the
nucleus, indicating translocation into ER. ATCYP5 was expressed mainly in young
stems especially in the apical region and weakly in leaves and roots.
PMID- 10189706
TI - Changes in in vivo DNA-protein interactions in pea phenylalanine ammonia-lyase
and chalcone synthase gene promoter induced by fungal signal molecules.
AB - Elicitor-induced protein bindings were detected on the several particular
sequence motifs in two members of the pea PAL and CHS gene promoters by in vivo
footprinting analyses. However, elicitor-induced changes rapidly reverted back to
the uninduced pattern after the subsequent application of suppressor from M.
pinodes.
PMID- 10189707
TI - Differential light regulation of the rbcS gene expression in two cell lines of
the liverwort Marchantia paleacea var. diptera.
AB - A cDNA of the small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase
(RuBisCO) gene (rbcS) was isolated from cells of the liverwort Marchantia
paleacea var. diptera. The rbcS was expressed light-independently in a green
line, but light-dependently in a yellow line. The accumulation of the large
subunit of RuBisCO was regulated cooperatively with that of the small subunit.
PMID- 10189709
TI - Cloning and characterization of a seed-specific omega-3 fatty acid desaturase
cDNA from Perilla frutescens.
AB - A cDNA encoding omega-3 fatty acid desaturase was isolated from developing
perilla seeds and characterized. On the basis of its deduced amino acid sequence
comparison, this cDNA was assumed to be a new isoform of microsomal omega-3 fatty
acid desaturase gene. Accumulation of the mRNA for this cDNA showed seed-specific
expression.
PMID- 10189710
TI - Mapping of 25 drought-inducible genes, RD and ERD, in Arabidopsis thaliana.
AB - We mapped 25 Arabidopsis thaliana drought-inducible genes. Responsive to
Dehydration (RD) and Early Responsive to Dehydration (ERD), to the Arabidopsis
genome and compared map positions with those of mutants that show environmental
stress response. We hybridized CIC yeast artificial chromosome (YAC) library
filters with the cDNAs and determined the map positions of 18 corresponding
genes. We screened the P1 library with 7 other clones and analyzed segregation of
their restriction fragment length polymorphisms (RFLP) in recombinant inbred (RI)
lines. One cDNA could be mapped because it had been sequenced by the Arabidopsis
genome sequencing program.
PMID- 10189712
TI - Evidence for mitochondrial DNA recombination in a human population of island
Melanesia.
AB - Mitochondrial DNA (mtDNA) analysis has proved useful in studies of recent human
evolution and the genetic affinities of human groups of different geographical
regions. As part of an extensive survey of mtDNA diversity in present-day Pacific
populations, we obtained sequence information of the hypervariable mtDNA control
region of 452 individuals from various localities in the western Pacific. The
mtDNA types fell into three major groups which reflect the settlement history of
the area. Interestingly, we detected an extremely rare point mutation at high
frequency in the small island of Nguna in the Melanesian archipelago of Vanuatu.
Phylogenetic analysis of the mtDNA data indicated that the mutation was present
in individuals of separate mtDNA lineages. We propose that the multiple
occurrence of a rare mutation event in one isolated locality is highly
improbable, and that recombination between different mtDNA types is a more likely
explanation for our observation. If correct, this conclusion has important
implications for the use of mtDNA in phylogenetic and evolutionary studies.
PMID- 10189711
TI - How clonal are human mitochondria?
AB - Phylogenetic trees constructed using human mitochondrial sequences contain a
large number of homoplasies. These are due either to repeated mutation or to
recombination between mitochondrial lineages. We show that a tree constructed
using synonymous variation in the protein coding sequences of 29 largely complete
human mitochondrial molecules contains 22 homoplasies at 32 phylogenetically
informative sites. This level of homoplasy is very unlikely if inheritance is
clonal, even if we take into account base composition bias. There must either be
'hypervariable' sites or recombination between mitochondria. We present evidence
which suggests that hypervariable sites do not exist in our data. It therefore
seems likely that recombination has occurred between mitochondrial lineages in
humans.
PMID- 10189713
TI - Lineage selection and the evolution of multistage carcinogenesis.
AB - A wide array of proto-oncogenes and tumour suppressor genes are involved in the
prevention of cancer. Each form of cancer requires mutations in a characteristic
group of genes, but no single group controls all cancers. This lack of generality
shows that the control of cancer is not an ancient, fixed property of cells. By
contrast, it supports a dynamic evolutionary model, whereby genetic controls over
unregulated cell growth are recruited independently through evolutionary time in
different tissues within different taxa. The complexity of this genetic control
can be predicted from a population genetic model of lineage selection driven by
the detrimental fitness effects of cancer. Cancer occurs because the genetic
control of cell growth is vulnerable to somatic mutations (or 'hits'),
particularly in large, continuously dividing tissues. Thus, compared to small
rodents, humans must have evolved more complex genetic controls over cell growth
in at least some of their tissues because of their greater size and longevity; an
expectation relevant to the application of mouse data to humans. Similarly, the
'two-hit' model so successfully applied to retinoblastoma, which originates in a
small embryonic tissue, is unlikely to be generally applicable to other human
cancers; instead, more complex scenarios are expected to dominate, with
complexity depending upon a tissue's size and its pattern of proliferation.
PMID- 10189714
TI - Monocular focal retinal lesions induce short-term topographic plasticity in adult
cat visual cortex.
AB - Electrophysiological recording in primary visual cortex (VI) was performed both
prior to and in the hours immediately following the creation of a discrete
retinal lesion in one eye with an argon laser. Lesion projection zones (LPZs; 21
64 mm2) were defined in the visual cortex by mapping the extent of the lesion
onto the topographic representation in cortex. There was no effect on neuronal
responses to the unlesioned eye or on its topographic representation. However,
within hours of producing the retinal lesion, receptive fields obtained from
stimulation of the lesioned eye were displaced onto areas surrounding the scotoma
and were enlarged compared with the corresponding field obtained through the
normal eye. The proportion of such responsive recording sites increased during
the experiment such that 8-11 hours post-lesion, 56% of recording sites displayed
neurons responsive to the lesioned eye. This is an equivalent proportion to that
previously reported with long-term recovery (three weeks to three months).
Responsive neurons were evident as far as 2.5 mm inside the border of the LPZ.
The reorganization of the lesioned eye representation produced binocular
disparities as great as 15 degrees, suggesting interactions between sites in VI
up to 5.5 mm apart.
PMID- 10189715
TI - Chromatography and electrophoresis on chips: critical elements of future
integrated, microfluidic analytical systems for life science.
AB - Liquid chromatography and electrophoresis played a major role in the life-science
revolution, most strikingly in protein purification, peptide fractionation and
sequencing, amino acid analysis, and DNA sequencing. The objective of this
article is to examine the potential role of separation systems in the continuing
evolution of biochemistry, biotechnology and molecular biology. Very small chip
based systems may change how chemical analyses in biology, medical research and
health care evolve over the next decade.
PMID- 10189716
TI - The selection of intracellular antibodies.
AB - The intracellular expression of antibodies in mammalian cells is a strategy to
inhibit the in vivo function of selected molecules but is limited by the
unpredictable behaviour of antibodies when intracellularly expressed. Recent
advances in the field of antibody expression in Escherichia coli show that the
introduction of mutations can improve the properties of some antibody domains,
but the general applicability of this approach to intracellular antibodies
remains to be proved. As a complement to rational approaches, we describe
selection schemes in which antibodies are selected on the basis of their
performance in vivo as intracellular antibodies.
PMID- 10189717
TI - Proteomics: quantitative and physical mapping of cellular proteins.
AB - Genome sequencing provides a wealth of information on predicted gene products
(mostly proteins), but the majority of these have no known function. Two
dimensional gel electrophoresis and mass spectrometry have, coupled with searches
in protein and EST databases, transformed the protein-identification process. The
proteome is the expressed protein complement of a genome and proteomics is
functional genomics at the protein level. Proteomics can be divided into
expression proteomics, the study of global changes in protein expression, and
cell-map proteomics, the systematic study of protein-protein interactions through
the isolation of protein complexes.
PMID- 10189718
TI - Powerful tools for genetic analysis come of age.
AB - Microscopic arrays of oligonucleotides or cDNA containing up to several hundred
thousand different sequences are starting to influence methodologies and paths to
discovery in genomics. Gene polymorphisms and mutations can be found and gene
expression measured with unprecedented speed and parallelism. The principles of
this modern technology and some of the problems awaiting further study are
discussed.
PMID- 10189719
TI - Antibiotic resistance pattern of foodborne Salmonella isolates in Addis Ababa
(Ethiopia).
AB - A total of 39 Salmonella cultures isolated from raw minced beef and chicken
(gizzard, liver, and heart) samples in Addis Ababa were examined for
susceptibility to a group of 10 selected antimicrobials. 34 isolates (87.2%) were
resistant to one or more antibiotics. The antibiotics to which isolated
Salmonella strains were most often fully resistant included nitrofurantoin
(48.7%), furazolidone (48.7%) and streptomycin (46.2%). Only 4 antimicrobials
(gentamycin, kanamycin, rifampicin and sulphamethoxazole-trimethoprim) were
effective against all Salmonella isolates with the exception of 2 which were
intermediate in resistance to kanamycin (1) and sulphamethoxazole-trimethoprim
(1). 77.8% of the S. Enteritidis strains showed multiple resistance to up to four
antibiotics followed by S. Typhimurium (60.0%) and S. Dublin (33.3%). The high
level of antibiotic resistance of foodborne Salmonella isolates in the study area
is an indication of indiscriminate and continuous use of subtherapeutic doses of
antibiotics in animals.
PMID- 10189720
TI - Case report: umbilical foreign-body granuloma in a lamb.
AB - An unusual case of umbilical foreign-body granuloma in a 3-week old lamb is
described. The most prominent clinical finding was a large fibrous mass which
bulged above the surface, adjacent to the umbilicus. Histologically, plant
material surrounded by histiocytes, plasma cells, giant cells and fibroblasts
were seen.
PMID- 10189721
TI - [Associations between farm characteristics in fattening pigs and occurrence of
lesions at meat inspection].
AB - A revised inspection system for fattening pigs in the EU has been proposed
emphasizing the need for a more detailed documentation of the fattening process.
It is supposed that the availability of such information enables a discrimination
of conspicuous and non-conspicuous lots of fattening pigs delivered to the
abattoir allowing for a modified, only visual inspection of non-conspicuous lots.
This proposal motivated a study performed in 1996 on about 22,000 pigs,
searching, among other things, for first hints on associations between
management/farm conditions for fattening pigs and lesions found at meat
inspection, which can be used for discrimination. Taking the two lesions
'pneumonia' and 'callous affections of the legs' as examples this contribution
demonstrates the use of regression trees to visualize association structures and
to develop hypotheses on relations between lesions and farm characteristics. An
association of 'callous affections of the legs' with flooring systems is clearly
shown in the generated tree. The occurrence of 'pneumonia' seems to be associated
with the application of disinfection measures in this data set. However, this
result should be interpreted with caution as some problems for data analysis
arise because of the low number of farms in this study in relation to the high
number and complexity of farm characteristics considered. A further problem is
the high variability of daily deliveries within farms that cannot be explained
referring to farm characteristics common to all deliveries. As a conclusion data
from this study have been useful to develop hypotheses on associations between
farm characteristics and lesions at meat inspection. However, there is need for
further, more specific studies before such associations can be utilized to
discriminate between conspicuous and non-conspicuous lots of fattening pigs.
PMID- 10189722
TI - [Comparison of laboratory diagnostic methods for the detection of infection with
the virus of classical swine fever in the early inspection phase: an experimental
study].
AB - Virus isolation in the PK-15 cell culture, two commercial antigen ELISAs, reverse
transcriptional-polymerase chain reaction (RT-PCR), and flow cytometry have been
evaluated to detect viremic pigs in the early period of classical swine fever
virus (CSFV) infection. Domestic pigs were experimentally inoculated with the
virulent CSFV strain 'Alfort 187' and two field isolates. CSFV isolation and RT
PCR were found to be the most sensitive methods for the detection of highly
virulent CSFV in the early period of infection which is characterized by the
absence of clinical symptoms. Using antigen ELISAs and flow cytometry CSFV could
be detected in infected animals after the onset of clinical signs. After
infection with a less virulent CSFV field isolate originating from wild boar,
viremic pigs could be identified by direct virus isolation. The reasons for the
negative results of the RT-PCR still remain unknown. In conclusion we recommend
to modify the procedure (antigen ELISA) for the detection of clinically healthy
domestic pigs in accordance with the decision 98/413/EC.
PMID- 10189723
TI - [Utilization of nylon membranes for the specific isolation of Escherichia coli
O157 with DNA probes and checking for relationship to the shiga toxin Escherichia
coli (STEC) group].
AB - A method for specific isolation of Escherichia coli strains of serotype O157 is
given. DNA-hybridization technique by using DIG-labeled specific O157 PCR
amplificates as probes is the basis. These investigations can be used for the
detection and isolation of shigatoxin-producing Escherichia coli (STEC) of this
serotype in combination with other tests for detection of shigatoxin genes (stx).
No background is seen by using 'DIG Easy Hyb' solution and Nylon membranes for
colony-and plaque-hybridization (Roche Diagnostics Boehringer Mannheim). Dark
brown spots (E. coli colonies) are visible on the membranes after staining. After
comparing the membrane with the masterplate it is possible to isolate the
colonies from the masterplate, respectively. It is necessary to make proof that
the isolates possess the rfb-genes (verification of serotype O157) and the stx
genes (test for belonging to the STEC-group). Both tests could be done by using
PCR. In case of positive results other virulence factors of the isolates can be
detected.
PMID- 10189724
TI - [Iodine deficiency, iodine requirement and iodine excess of farm animals-
experiments on growing pigs].
AB - Since insufficient iodine intake is widespread among the German population, farm
animals should if possible receive iodine above requirement, thus concentrating
the trace element in milk, eggs and possibly meat. Experiments with a total of 29
fattening pigs with grain soy-bean meal diets without iodine supplementation or
with increasing supplements up to 1000 micrograms iodine/kg diet did not show any
effect on growth intensity (gain) and feed efficiency. At and above 125
micrograms supplementary iodine/kg diet the thyroid was not or only little
hypertrophied and iodine incorporation into thyroglobulin sufficed to sustain
serum T4 concentration. The glucosinolates of rape feeds increase iodine
requirement. In an experiment with a total of 36 fattening pigs the thyroid
iodine depot was decreased due to rapeseed meal feeding, this in agreement with
antithyroid drugs which had been also tested. A thyroid with emptied iodine depot
is hardly able to synthesize and release hormone, the serum thyroxine
concentration showed a drastic decrease. More iodine may compensate for effects
of glucosinolates, however, only with not too much of these compounds in the
feed. Excessive iodine dosages (10 mg/kg diet) were compared with supplements in
the range of recommendations (100 and 1000 micrograms/kg diet) with a total of
120 pigs in three groups of 40 animals each. The dosage of 10 mg iodine/kg diet
decreased serum T3 concentration. The enlarged thyroid with double weight had a
very high iodine concentration. In comparison with physiological application (100
or 1000 micrograms iodine/kg diet) the thyroid deposited only little iodine in
the group with the excessive iodine intake related to consumed iodine quantity.
In case of sufficient and excessive iodine supply--industry of compounds feed
applies up to 2.5 mg supplementary iodine/kg diet--T4 and iodine of serum but
also thyroid weight cannot serve as markers. This range of usual iodine supply is
better characterized by the iodine depot of the thyroid. As a rule, thyroid
weight increase indicates glucosinolate effects, generally those of dietary
antithyroid compounds, more seldom it shows extreme and longterm iodine
undersupply or iodine excess.
PMID- 10189725
TI - Physicians and the Roman imperial aristocracy: the patronage of therapeutics.
PMID- 10189726
TI - Gabriele Zerbi's De cautelis medicorum and the tradition of medical prudence.
PMID- 10189727
TI - "The Great Arcana of the Deity": menstruation and menstrual disorders in
eighteenth-century British medical thought.
PMID- 10189728
TI - The infirmary of the Glasgow Town's Hospital, 1733-1800: a case for voluntarism?
PMID- 10189729
TI - The Nuremberg doctors' trial in historical context.
PMID- 10189730
TI - The Living City: engineering social and urban change in New York City, 1865 to
1920.
PMID- 10189731
TI - Population health: determinants and interventions.
PMID- 10189732
TI - Public perceptions of the relationship between poverty and health.
AB - The public's view on how poverty and health are related will influence support
for different policies and programs. The purpose of this study was to examine
public perceptions of the relationship between poverty and health and to identify
demographic variables that predict support for the four explanations of the
relationship between poverty and health (artifact, drift, behavioural, and
structural) first identified in the Black Report in the United Kingdom. A
telephone survey of a representative sample of Albertans (N = 1,216) was
conducted. The majority of respondents believed that poverty leads to poor
health. The explanation that health is influenced by the context in which
individuals live (structural) received the most support. Demographic variables
(sex, age, education, occupation, income, residence, conservatism) explained less
than 10% of the variance for each of the four explanations, with conservatism the
most consistent predictor.
PMID- 10189733
TI - Social and cultural vulnerability to sexually transmitted infection: the work of
exotic dancers.
AB - This article examines the social and cultural factors that influence the
vulnerability of female exotic dancers to sexually transmitted infections.
Results are based on a qualitative, exploratory study using observations in 10
clubs and in-depth interviews with 30 dancers in southern Ontario. The social and
cultural context within which exotic dancing takes place contributes to a chronic
state of sexual harassment and sexual assault in the strip clubs. Women are
pressured by economics and by their customers to engage in sex for pay. The
defence mechanisms that some women use to deal with these work conditions also
contribute to women's vulnerability. The social structure of strip clubs and
their policies toward employees and customers can either reduce or exacerbate the
vulnerability of dancers. Workplace policies and health and safety standards
appear to be the most effective ways to decrease the vulnerability of dancers.
Public health units can work with employers and dancers to establish workplace
policies and programmes that contribute to the health and wellbeing of dancers.
PMID- 10189734
TI - [Structuring action from using a model for planning health promotion programs].
AB - The aim of this paper is to present results which illustrate the role of the
PRECEDE-PROCEED model in the program planning process. Based on the results of an
implementation evaluation of the EMPOWER software which supports health
programming efforts, we have developed a metaphor to illustrate the use of the
model. The following four functions of the model were identified: direction,
coordination, articulation and transmission. Analysis of these functions
demonstrated the structuring action of the model on planning. It would be
interesting to further study how these four functions operate with or without the
support of the software, to explore the influence of other health promotion
models in their natural settings and to see in which way the same or other
functions might be identified.
PMID- 10189748
TI - Traumatic experiencing and post traumatic psychological symptoms in South African
University students.
AB - OBJECTIVES: Traumatized and nontraumatized subjects were compared on post
traumatic stress disorder (PTSD) symptoms, depression and anxiety. In addition,
gender differences, socio-economic and family background were studied. DESIGN:
Cross sectional. SETTING: University of the North. SUBJECTS: All first year
African psychology students comprising of 82 (31%) male and 180 (69%) females in
the age range 17 to 25 years (mean age 20.7 years, SD = 2.3). MAIN OUTCOME
MEASURES: The Impact of Event Scale (IES), the 35 item civilian version of the
Mississippi Scale for PTSD, and the 42 item Symptom Rating Scale for Depression
and Anxiety. RESULTS: Results indicated a high life time prevalence of traumatic
events (56% of the students). Males were significantly more likely than females
to be in an accident (26.8% vs 11.7%, p = 0.004). Females were more likely than
males to have experienced an unexpected death of a significant other (27.8% vs
11.0%, p = 0.003) and to have been raped (6.0% vs 0%, p = 0.021). There was a
significant positive relationship between exposure to traumatic events and post
traumatic stress symptoms. Melancholia and anxiety were both significantly
related with PTSD measures indicating comorbidity. Thirty two (12%) fulfilled the
criteria for PTSD according to the Mississippi Scale for PTSD. CONCLUSION: A high
incidence of traumatic events and PTSD symptoms associated with melancholia and
anxiety was found in a nonclinical first year university student population
indicating a need for trauma intervention.
PMID- 10189749
TI - Significance of polymicrobic bacteriuria in a teaching hospital in Trinidad.
AB - OBJECTIVE: To compare microbial prevalence (mixed versus pure), define microbial
combination in mixed urine cultures among inpatients and outpatients and to
identify factors that might allow a more objective interpretation of polymicrobic
urine cultures. DESIGN: Case series. SETTING: The study involved inpatients
(hospitalized) and outpatients (those attending outpatient clinics and the
accident and emergency department) of the San Fernando General Hospital in
southern Trinidad. MAIN OUTCOME MEASURES: Prevalence rates of bacterial isolates
in mixed and pure cultures of urine specimens were determined using standard
techniques and Kirby-Bauer disc diffusion methodology. RESULTS: The results
obtained showed that of 5,089 urine specimens, 1,491 (29.3%) yielded positive
cultures. Of these positive cultures, 524 (35.1%) revealed significant
polymicrobic bacteriuria. Eighty five percent yielded two organisms, 13.2% had
three organisms and 1.8% had four organisms. Repeat cultures in 157 patients
revealed the same organisms in only 57.3% of them. Almost all of the repeat
cultures were from patients with in-dwelling Foley catheters. E. coli was the
most common single isolate (42.8%), while Klebsiella, Enterobacter and Proteus
organisms were most often encountered in mixed cultures. All isolates were
relatively sensitive to routinely used antibiotics for urinary pathogens.
CONCLUSION: The prevalence rate of polymicrobic bacteriuria at our institution
was 10.2%. More than 65% of positive cultures were from patients with Foley
catheters on open drainage (inpatients) and closed drainage (outpatients). Most
were men with out-flow obstruction who either refused surgery, were unfit for
surgery, or had to wait long periods to be booked for surgery. No cases developed
bacteremia secondary to bacteriuria. All urinary isolates were susceptible to
routinely used antimicrobial agents.
PMID- 10189750
TI - Hairy cell leukaemia in the Bloemfontein academic hospitals.
AB - OBJECTIVES: To study the clinical presentation, treatment and outcome of patients
diagnosed with hairy cell leukaemia (HCL) in the Bloemfontein Academic Hospitals
during the past 21 years. DESIGN: Retrospective study. All HCL patients diagnosed
from 1975 to 1996. SETTING: Haematology clinics of the Universitas and Pelonomi
Hospitals in Bloemfontein. SUBJECTS: All HCL patients diagnosed from 1975 to
1996. MAIN OUTCOME MEASURES: To determine the clinical and demographic profile,
as well as response to treatment, of HCL patients in this region. RESULTS: A
total of 16 HCL patients were studied. There were more males (13) than females
and the mean age of the patients was 58 years (35 to 82 year; SD14.8). No Black
patients were diagnosed. The patients mostly presented with a cytopenia and
splenomegaly was present in 12 of the 14 patients for which spleen size was
noted. All of the patients had a splenectomy and six were also treated with 2'
deoxycoformycin (Pentostatin). All six of the patient showed a response to
treatment with this purine analogue. CONCLUSIONS: The presentation of HCL in the
Bloemfontein academic hospitals is similar to what is seen world-wide. However,
to evaluate the durability of the response to treatment with the purine
analogues. Long term follow up is needed.
PMID- 10189751
TI - Paracolic abscesses from spontaneous perforation of granulomatous colitis.
AB - Three cases of spontaneous perforation of granulomatous colitis are presented.
The typical features are those of acute right iliac fossa pathology mimicking
appendicitis. Differential diagnosis is difficult in our locality but includes
essentially Crohn's colitis although tuberculous and other inflammatory colitis
could not be definitively excluded. In the absence of facilities for laparoscopy
or even ultrasound-guided percutaneous drainage the results of open laparotomy
with right hemicolectomy were beneficial. As expected in our community follow up
responses were poor making it difficult to predict long term outcomes. A plea is
made for practitioners to bear unusual pathologies in mind during practice.
PMID- 10189752
TI - Retrosternal thyroid carcinoma metastatic to the sternum: a case report.
AB - A 75 year old female patient presented with a pulsatile sternal mass. The
resected mass was a metastatic follicular carcinoma of thyroid origin. The
primary tumour was found in the retrosternal area. The differential diagnosis of
a sternal tumour is discussed.
PMID- 10189753
TI - Syndromic management of sexually transmitted diseases. Part 4--The management of
lower abdominal pain in women.
AB - The symptom of lower abdominal pain in women is extremely common and does not
always indicate the presence of serious illness. However, women with certain
serious conditions such as pelvic inflammatory disease (PID), acute appendicitis,
ectopic pregnancy and other complications of pregnancy may present initially with
this symptom. Therefore, in managing women with lower abdominal pain care should
be taken to exclude any serious condition before dismissing the patient. PID is a
condition in which there is infection of the reproductive tract of women above
the internal os of the cervix. This usually occurs as a result of an ascending
cervical infection caused by Neisseria gonorrhoeae, Chlamydia trachomatis and
anaerobic bacteria. The immediate and long term effects of PID include
salpingitis, pelvic abscess, peritonitis, infertility and predisposition to tubal
ectopic pregnancy. Women with lower abdominal pain should be assessed carefully
and if PID is the cause they should be treated for gonococcal, chlamydial and
anaerobic bacterial infection. Other gynaecological and surgical causes of lower
abdominal pain and the immediate complications of PID require urgent referral to
a specialist. PID is associated with significant morbidity and mortality.
PMID- 10189754
TI - Zimbabwean people with head noises are offered help.
PMID- 10189770
TI - Use of inhaled nitric oxide for the treatment of persistent pulmonary
hypertension of the newborn (PPHN).
PMID- 10189771
TI - Absorbable fasteners for the fixation of ankle fractures.
AB - Bioabsorbable materials have been used for the treatment of fractures for more
than a century. We reviewed the results of a combined series of 30 ankle
fractures from Bad Hersfeld, Germany, and Louisville, Kentucky, using initially
polyglycolide and more recently poly-L-lactide screws and rods. The results were
comparable to treatment with metal screws. The advantage of bioabsorbable
implants is they do not need operations to take them out. There was a low
incidence of reaction around the screw heads, which was reduced further with the
use of the newer self-reinforced poly-L-lactate screws. The technique for use of
plastics is different than the methods for placement of metal screws.
Bioabsorbables will have an increasing role in fracture fixation in the future.
PMID- 10189772
TI - Population attitudes toward oncology clinical trials.
AB - OBJECTIVE: We examined the attitudes of the Kentucky adult population toward
experimental oncology treatment and randomized clinical oncology trials. DESIGN:
We conducted a health survey of 654 noninstitutionalized adults randomly selected
from Kentucky households. We posed to them a series of questions evaluating
demographics, general health, and personality characteristics. We asked specific
questions to characterize the subjects' experiences with cancer, their desires
for autonomy in medical treatment, their health-related behaviors, and their
preconceived opinions about specific cancer screening examinations. We then asked
the subjects about their willingness to undergo experimental treatment and their
willingness to participate in a randomized clinical oncology trial within the
framework of a defined, specific oncology scenario. RESULTS: Of our subjects, 73%
were willing to consider an experimental form of therapy of indeterminate
benefit; however, only 39% were willing to consider a randomized clinical trial
of two therapies, given the same oncology scenario. The influences of demographic
factors, general health, personality factors, personal experience with cancer,
and desire for autonomy in health care were found to be of minimal importance in
predicting a willingness to participate. CONCLUSIONS: A strong negative bias
toward randomized clinical trials appears to exist within this population.
Continued public education regarding the value of clinical trials to the
individual, as well as their selfless benefit to humanity, is clearly needed.
PMID- 10189773
TI - Art vs science.
PMID- 10189774
TI - Costs of smoking: a focus on maternal, childhood, and other short-run costs.
AB - Estimating the costs attributable to smoking is helpful for evaluating
appropriate tax policy, informing both public and private managers of health
care, and evaluating alternative smoking cessation programs. While the smoking
attributable costs of chronic conditions have been well studied, these costs are
less relevant to health maintenance organizations (HMOs) and employers whose
populations are younger and transient. Costs incurred in the short run, such as
those related to smoking during pregnancy and environmental tobacco smoke
exposure (ETS) of children, are more relevant. In this article, the authors
review studies of these sources of smoking-attributable costs as well as studies
that focus on smoking-attributable outcomes and costs from the employer or HMO
perspective. Subsidies may be necessary to induce employers to recognize the full
social benefits of smoking cessation programs.
PMID- 10189775
TI - Drive-through delivery: where are the "savings"?
AB - Using a natural experiment, this study estimates the effects of Medicaid managed
care on total hospital costs of a birth. The authors study 5,585 vaginal
deliveries from 1993 through 1995. Hospital length of stay for maternity care has
been reduced by 21 percent after the introduction of managed care. The resultant
program saving, however, is $280 in total hospital cost per delivery, 12 percent
of the total hospital costs before managed care. Furthermore, when the full costs
of an earlier discharge, including costs to patients and their families, are
taken into account, the savings associated with a shortened hospital stay may be
even smaller.
PMID- 10189776
TI - Commentary: "efficiency and civility in maternity care" or "how much jello can a
mother eat?".
PMID- 10189777
TI - Children's health insurance coverage and family structure, 1977-1996.
AB - Using data from a series of nationally representative medical expenditure
surveys, the authors document changes in children's health insurance coverage in
a period of two decades. Overall, it is found that the proportion of children
with private coverage declined, while the proportions publicly insured and
uninsured increased. However, when the authors account for differences in family
structure, they find striking disparities in children's insurance experiences.
Contrary to overall trends, children in single-parent households made significant
gains in private health insurance coverage after 1997 and experienced reductions
in public insurance. Coincident with Medicaid expansions in the late 1980s,
children in two-parent households experienced significant increases in public
health insurance. It is found that the rise in the proportion of children who
were uninsured in this period was largely a single-parent family phenomenon, and
that parents' marital status, employment status, and family income are crucial
factors associated with children's insurance status.
PMID- 10189778
TI - Evaluating the effect of usual source of dental care on access to dental
services: comparisons among diverse populations.
AB - Data collected from the International Collaborative Study of Oral Health Outcomes
USA (ICS-II) research locations were used to evaluate the relationship between
having a usual source of dental care (USDC) and access to dental services. The
robustness of the USDC effect after reducing simultaneity bias was tested in the
population-based samples using sensitivity analysis. Logistic regression results
provided evidence that USDC was the strongest and most consistent predictor of a
dental visit in the past 12 months regardless of geographic location, dental care
delivery system, or cultural diversity of the population. Even removing cases
that had a USDC for less than 1 or 2 years, the effect remained. From a policy
perspective, USDC remains critical to understanding and explaining dental are
utilization patterns. The findings suggest the need for designing interventions
to increase the availability of a regular provider among vulnerable populations.
PMID- 10189779
TI - Do market-level hospital and physician resources affect small area variation in
hospital use?
AB - This study evaluates the effect of market-level physician and hospital resources
on hospital use. It is anticipated that higher hospital discharges are associated
with (1) greater hospital and physician resources, (2) more differentiated
hospital and physician resources, and (3) higher levels of teaching intensity in
the community. Data on 14 modified diagnostically related groups (DRGs) and 58
hospital market communities in Michigan are analyzed during a 7-year period.
Findings indicate that physician resources, hospital resources, differentiation
of hospital and physician resources, and teaching intensity contribute only
modestly to discharges, holding constant the socioeconomic attributes of the
community and adjusting for the variation in hospital use over time. With the
inclusion of hospital and physician resource variables, socioeconomic factors
remain important determinants of the variation across market communities.
Findings are discussed in terms of their implications for health care
organizations, managed care programs, and cost control efforts in general.
PMID- 10189780
TI - Generic measures to compare burden of disease.
PMID- 10189781
TI - Impairment of quality of life: rheumatoid arthritis versus sarcoidosis.
AB - BACKGROUND: Quality of life (QOL) has become an important item in health care.
QOL should be a major target of treatment in chronic diseases such as rheumatoid
arthritis (RA) and sarcoidosis. The aim of this study was to compare the impact
of RA and sarcoidosis on patients' QOL. We expected more serious impairment of
QOL in the RA group than in the sarcoidosis group. METHODS: QOL was studied in RA
patients (n = 32), sarcoidosis patients (n = 37), and a healthy control group (n
= 37) employing the World Health Organization Quality of Life assessment
instrument (WHOQOL-100). RESULTS: In both patient groups QOL was impaired with
respect to Physical Health, Level of Independence (P < 0.001), and Overall QOL
and General Health (P < 0.01). Moreover, RA patients appeared to have a lower QOL
with respect to Pain and Discomfort (P < 0.001) and Mobility (P < 0.001).
CONCLUSIONS: In RA and sarcoidosis, fatigue and sleep were major problems. In
contrast to our expectations, with respect to activities of daily living and
working capacity, the two patient groups did not show any difference. Impairment
of QOL was more serious and included more aspects of QOL in RA than in
sarcoidosis.
PMID- 10189782
TI - Diagnostic value of endoscopic signs of gastritis: with special emphasis to
nodular antritis.
AB - BACKGROUND: Antral nodularity in children is described to have a high correlation
with active H. pylori infection. Data on antral nodularity in adults are sparse.
PATIENTS/METHODS: A cross-sectional study was done in order to determine
sensitivity (sens), specificity (spec), positive (PPV) and negative (NPV)
predictive value of macroscopic signs of gastritis (nodularity, erosions,
intramucosal haemorrhage, redness). Antral biopsy specimens for HE, Gram's stain
and culture were taken irrespective of endoscopic diagnosis. The macroscopic
aspect of the antrum was noted explicitely. RESULTS: In 305 consecutive patients
antral biopsy specimens were taken. In 218 (71.4%) the macroscopic appearance of
the antrum was normal, 65 (29.8%) of them were positive for H. pylori. The
remaining 87 patients (28.6%), 58 (67%) of them H. pylori positive, showed antral
abnormalities. The presence of an macroscopically abnormal gastric antrum and
presence of antral nodularity had a sens of 39.8%, a spec of 83.6%, a PPV of
72.4%, a NPV of 56.4% and a sens of 19.6%, a spec of 98.6%, a PPV: 93.9% and a
NPV: 53.3% respectively with respect to histological gastritis. CONCLUSIONS:
Endoscopic signs of gastritis have low sensitivity but relatively high
specificity. Antral nodularity is the only sign with a high positive predictive
value for H. pylori infection.
PMID- 10189783
TI - Hyponatraemia. Comments on two case reports.
PMID- 10189784
TI - Beer drinker's hyponatraemia: a case report.
AB - Beer drinker's hyponatraemia, also called beer potomania, is a syndrome of
hyponatraemia in patients who consume excessive amounts of beer and have a poor
dietary intake. We describe a patient with chronic asymptomatic hyponatraemia due
to beer potomania. The pathophysiology of this syndrome, the treatment and
prevention are reviewed.
PMID- 10189785
TI - Severe hyponatraemia in an amiloride/hydrochlorothiazide-treated patient.
AB - A 85-year-old woman treated with, among other drugs, a thiazide diuretic
presented with a severe hyponatraemia. She met several of the criteria for SIADH
and, besides drugs, no cause for SIADH was found. After stopping the thiazide
diuretic and restricting fluid intake the patient recovered fully. It was later
proved that the thiazide was the cause of the water intoxication by rechallenging
the patient with a single dose of amiloride/hydrochlorothiazide 5/50 mg. This
"thiazide provocation test" showed its usefulness in the differential diagnosis
of suspected SIADH. Moreover, the test demonstrated the paradoxal effect of
thiazide diuretics to cause water retention in susceptible patients.
PMID- 10189787
TI - Ulcerative colitis and acquired demyelinating neuropathy (Guillain-Barre
syndrome)
PMID- 10189786
TI - The pathogenesis of progressive renal failure.
AB - All glomerular kidney disorders with the exception of minimal change disease are
characterized by a progressive decline of renal function in association with
progressive glomerulosclerosis and tubulointerstitial fibrosis of the kidneys
involved. This almost universal association seems to suggest that the progressive
loss of kidney function results from a fibrogenic pathogenetic mechanism that
serves as a final common pathway with the initial insult to the glomerulus
initiating a cascade of events including an early inflammatory phase followed by
a fibrogenic response in the glomerular and the tubulointerstitial compartments
of the kidneys. The present review will address the pathogenesis of this
fibrogenic process covering the interplay between glomerular and
tubulointerstitial events, the roles of recruited and resistant cells, cytokines,
growth factors and the extracellular matrix.
PMID- 10189788
TI - Images in clinical medicine. All-trans-retinoic acid related pulmonary syndrome
in acute promyelocytic leukemia.
PMID- 10189789
TI - [Preoperative radiotherapy of cancer of the rectum. What if Europe is right?].
PMID- 10189790
TI - [The history of the Saint-Jacques de Besancon Hospital].
PMID- 10189791
TI - [Definition, description and classification of endometriosis].
AB - The presence of ectopic endometrial tissue defines endometriosis. External
endometriosis, the real one, can be observed everywhere in the woman body and in
genitourinary tract in man. Macroscopic and histologic features depend on their
duration, on their location and the period of the menstrual cycle. All the
changes of eutopic endometrium can be exhibited by endometriotic foci: response
to hormonal stimuli, decidualization, malignant transformation (neoplasm arising
from endometriosis).... The revised American Fertility Society classification,
most frequently used, establishes scores assigned to ovarian and peritoneal
lesions. Adenomyosis or internal endometriosis involves the myometrium. This
peculiar entity represents a diverticulosis of the endometrium into myometrium
with smooth muscle hyperplasia.
PMID- 10189792
TI - [The mechanisms of endometriosis].
AB - Endometriosis is characterised by the presence in abnormal situation of a tissue
resembling the endometrium with glands and stroma. Several assumptions try to
explain the development of this tissue. The oldest, the theory of the metaplasia,
suggests that under various influences the coelomic tissues would be transformed
into endometrium. Most often agreed, the theory known as the implantation theory,
explains why the endometrial cells and fragment desquamated during menstrual
period transported through the fallopian tubes into the peritoneal cavity
(physiological phenomenon) could under certain conditions implant, proliferate
and develop overcoming the local mechanisms of defence. The peritoneal cavity of
the normal women have the capacity to prevent the evolution towards
endometriosis. The reasons of an evolution towards the endometriosis and its
symptoms (pain, sterility, adherences are probably numerous implying the immune
system, the endometrium, the macrophages, the cells natural killer, the
peritoneum the fallopian tubes. The failure to removes the peritoneal cavity of
the fragments would induce an inflammatory local state with hyperactivation of
the macrophages which secrete many molecules, of which some could lead the
metaplasia of the peritoneum or the development of mullerian residues.
PMID- 10189793
TI - [Clinical presentation and natural history of endometriosis].
AB - Natural history of endometriosis is unpredictable. Some recent data show that
endometriosis is a progressive disease. Minimal lesions are transient and
peritoneal implants are reorganized continuously. So, minimal endometriosis could
be considered like a transient statement close to physiology. In favourable
statement such as the decreased activation of NK cells, the variable secretions
of cytokines, pelvic macrophages and growth factors, the peritoneal implants
evoluted like a progressive disease until severe endometriosis. Endometriosis is
a frequent cause of pelvic pain with dysmenorrhea, dyspareunia, chronic pelvic
pain and infertility. The diagnosis can be suspected by a clinical examination
preferentially during menstruation with fixed uterine retroversion peritoneal
infiltration, retraction of the rectum and retrovaginal endometriosis, and
adnexal cyst.
PMID- 10189794
TI - [Paraclinical studies of endometriosis].
AB - Investigations are performed in women with external endometriosis to confirm the
diagnosis and to evaluate extension of the disease before treatment. Elevated
serum CA 125 level is correlated with the severity of the disease. CA 125 may be
a helpful to assess the efficacy of the treatment or to detect recurrences.
Imaging diagnosis of endometriosis have a good sensitivity to detect cysts and
nodes forms of the disease. Magnetic resonance imaging is more sensitive than
ultrasonography to detect small nodular lesion and is able to made the diagnosis
of deeply infiltrating endometriosis (sometimes not visualised by laparoscopy).
Rectal endosonography, barium enema or excretion urography can be usefull if an
involvement of the rectosigmoid or the bladder is suspected.
Hysterosalpingography is an integral part of the initial fertility survey, but
shows only indirect signs of endometriosis. Laparoscopy is the definitive
diagnosis procedure for endometriosis, and permit to classify the lesions and to
draw-up a therapeutic strategy.
PMID- 10189795
TI - [Medical treatment of endometriosis].
AB - Medical treatment of endometriosis has been applied since 40 years. Its rational
is based upon the hormone-dependency of the endometriotic lesions inducing a
resting status. Adhesions, endometriomas or fibrous sequellae do not respond to
medical treatment. Its use in case of associated infertility is very limited.
Numerous agents are available for clinical use. Progestins are efficient on
pelvic pain, contra-indications, clinical and metabolic tolerance are linked to
the hormonal activity of the molecules. They have a low cost. Newer pills deserve
to be evaluated. Danazol has now few indications in regards to its clinical and
metabolic side-effects. Gn-RH analogs bear a potent efficacy and a very low
intrinsic toxicity. They are preferentially used in severe cases, in association
with surgery and before an IVF. Add back therapy improves the clinical tolerance
and reduces bone mass loss. Many parameters should be taken into account when
selecting a specific modality.
PMID- 10189796
TI - [Surgical treatment of endometriosis].
AB - The treatment of first intention for endometriosis must be surgery. In cases of
infertility the surgical treatment of choice is laparoscopic surgery, maybe in
conjunction with the medical treatment and possibly followed-up by a second-look.
When there is pelvic pain, the treatment relies on complete exeresis of the
endometriotic lesions. In this context, laparoscopic surgery is as efficient as
laparotomy for dealing with ovarian endometriomas, deep endometriosis
infiltrating the uterosacral ligaments, the rectovaginal septum and the bladder.
However, in the majority of cases bowel endometriosis is still an indication to
operate by laparotomy.
PMID- 10189797
TI - [Endometriosis and sterility].
AB - The relation between endometriosis and sterility is still unclear, especially in
minimal and mild forms. When the decision to treat endometriosis is made, the
question about how to treat raises. An hormonal treatment of minimal or mild
endometriosis seems not to improve fertility. However, laparoscopic destruction
of all visible peritoneal lesions seems to be usefull. The different result of
these two treatments is unexplained at this time. A complementary hormonal
treatment after laparotomy for severe endometriosis does not improve fertility.
PMID- 10189798
TI - [Adenomyosis].
AB - Adenomyosis keeps a strange and unknown feature. Indeed, therefore of an unclear
physiopathology, the difficult diagnosis due to the lack of specificity of
symptoms and the absence of effective conservative treatment, adenomyosis is
still tightly bond at hysterectomy. Even so, a recent literature study shows that
the fatality of hysterectomy could go away. The progress in imagery diagnosis and
myometrial biopsy allows the use of less radical treatments. So a group of young
patients with an earlier diagnosis appears, permitting to use with effectiveness
the hormonal therapy or endoscopic surgery. Hysterectomy at once is saved for
more than 40 years old patients, with a considerable uterine volume and deep
lesions. In the others cases, the radical procedure remains the solution for the
failure of conservative treatment.
PMID- 10189799
TI - [The National Health Conference and the financial laws of Social Security].
PMID- 10189800
TI - [Cancer of the prostate. Diagnosis, prognosis, principles of treatment].
PMID- 10189801
TI - [Pregnancy. Diagnosis, clinical surveillance, indications of complementary tests,
strict monitoring].
PMID- 10189802
TI - [Acute pancreatitis. Etiology, diagnosis, prognosis].
PMID- 10189803
TI - [Alcoholic cirrhosis. Pathologic anatomy, diagnosis, complications and their
physiopathology, treatment].
PMID- 10189804
TI - [Torsion of the spermatic cord. Diagnosis, emergency treatment].
PMID- 10189805
TI - [Injuries and open wounds of the abdomen. Diagnosis, management in an emergency
situation].
PMID- 10189806
TI - [Chronic myeloid leukemia. Diagnosis, course, prognosis].
PMID- 10189807
TI - Testing a model: effects of pain on immunity in HIV+ and HIV- participants.
AB - In this study, the cold pressor test (CPT) was used to test a model of the
effects of acute pain on 10 HIV+ and 10 HIV- adults. Participants were exposed to
the CPT for a maximum of 5 minutes. Blood samples were collected immediately
before, immediately after, and 1 hour after the CPT. Variables included immune
measures (CD4+, CD8+, and CD16+ 56+ lymphocyte number, CD4+ CD8+ lymphocyte ratio
and NK cell cytotoxicity), cardiovascular reactivity (heart rate, systolic and
diastolic blood pressure), anxiety, perceived pain intensity and perceived self
efficacy. Effects of pain were generally consistent across HIV+ and HIV- groups,
with no between-group differences across time in immune responses, state anxiety
and diastolic blood pressure. Within-subjects differences across time averaged
over both groups were significant for NK cell cytotoxicity, CD8+ and CD16+ 56+
lymphocyte numbers, anxiety and heart rate. Significant nonlinear trends were
observed for CD16+ 56+ lymphocyte numbers, NK cell cytotoxicity and state anxiety
in both groups and for heart rate in the HIV+ group only. Perceived pain
intensity was significantly associated with state anxiety (r = .65), systolic (r
= -.56) and diastolic (-.52) blood pressure and CD4+ lymphocyte number (r = .48).
Heart rate and trait anxiety were significantly associated with all immune
variables. Associations were positive for CD4+ lymphocyte number and inverse for
all other immune measures. Associations between perceived self-efficacy and both
perceived pain intensity and anxiety were inverse, as predicted, but not
significant. Overall, the direction and strength of observed relationships
provided some support for the theoretical model on which the study was based.
Generally, responses to acute pain were consistent and did not differ by HIV
status.
PMID- 10189808
TI - Wives, husbands, and daughters of dementia patients: predictors of caregivers'
mental and physical health.
AB - The purpose of this study was to investigate differences in and predictors of
mental and physical health among wife, husband, and daughter caregivers of
dementia patients using a stress and coping framework. The sample of 151
caregivers consisted of 55 wives, 43 husbands, and 53 daughters and was recruited
from multiple community-based sources. Variables addressed were caregiver age,
social position, years spent in caregiving, dementia severity, burden, worry,
physical health, and mental health. Analysis of variance demonstrated gender
specific, kinship group differences in burden (F = 8.09, p = .000), worry (F =
6.287, p = .002), and age (F = 55.27, p = .000). Post hoc comparisons indicated
that wives reported worrying most, while husbands were oldest and reported the
least burden. Health predictors differed by group, with wives' mental health
being predicted by severity of dementia, age, and worry (R2 = .16), husbands'
mental health was predicted by burden and worry (R2 = .18); and worry was the
only significant predictor of daughters' mental health (R2 = .33). Wives'
physical health was predicted by years of caregiving and age (R2 = .10);
husbands' physical health was predicted by age and worry (R2 = .24); and
daughters' physical health was predicted by years spent in caregiving and burden
(R2 = .27). Findings suggest that a stress and coping framework is a better
predictive model for daughters' mental and physical health than for health of
wives and husbands. Findings further indicate that different health-related
nursing interventions may be required for different caregiver groups.
PMID- 10189809
TI - Skilled carers' ways of understanding people with Alzheimer's disease.
AB - Five carers in a group dwelling for people with dementia were observed and
interviewed concerning their interactions with five residents with Alzheimer's
disease. The tape-recorded and transcribed data were analyzed as text. The
carers' personal ways of achieving understanding were defined as: affect
attunement; affect attunement and completing a puzzle through explanatory
connections of observation, knowledge about the residents' life histories and
behavior at the group dwelling; and affect attunement within the context of
caring as an intrinsic end. Personal experience from childhood and motherhood,
knowledge about the residents' life history and the nature of the disease, and
personal talent seemed to form these carers' ways of achieving understanding.
PMID- 10189810
TI - Nursing and communication: a reflection.
PMID- 10189811
TI - The influence of social class, strain and social support on symptoms of anxiety
and depression in mothers of toddlers.
AB - BACKGROUND: The aim of the study was to identify risk and protective factors for
anxiety and depression among mothers of toddlers. METHODS: A population-based
sample of 921 Norwegian mothers with 18-month-old children completed a
questionnaire designed to examine the impact of socioeconomic and demographic
factors, somatic health problems, negative life events, chronic strain and social
support on symptoms of anxiety and depression (HSCL-25). RESULTS: There was a
moderate aversive effect of negative life events and chronic strain and a
moderate protective effect of social support on the symptom level, but no
interaction effects were found between the risk and protective factors. Behaviour
problems among the children clearly seemed to affect the mothers' symptom level.
The symptom level varied with background factors like the mothers' education,
employment status and age even after controlling for the effect of strain and
social support. The largest effect of the background factors seemed to be
indirect, however, mediated through their effect on the risk and protective
factors. CONCLUSIONS: Although problems with the children's behaviour and child
care arrangements were observed to have a strong impact on the mothers' symptom
level, the frequencies of such problems appeared to be less dependent on
socioeconomic conditions than did other types of strain.
PMID- 10189812
TI - Significant others of suicide attempters: their views at the time of the acute
psychiatric consultation.
AB - As part of the psychiatric assessment after a suicide attempt contact with a
significant other could be of importance in order to obtain an additional view of
the patient's situation, and thereby possibly broadening the basis of the
assessment. The aims of this study were to investigate whether information from a
significant other would be helpful in the psychiatric assessment of the patient,
and also in assessing the well-being of significant others and their need for
support. For the purposes of the study, the significant other (SO) who had been
recommended by the patient was contacted directly after the suicide attempt.
Almost all the patients (95%) agreed to a social worker contacting an SO, and all
the contacted SOs (n = 81) agreed to take part in the study. A semi-structured
interview was performed by telephone or in person on the same occasion as we
interviewed the patient or as soon as possible afterwards. The study found that
the SOs provided valuable additional information regarding the patient's
situation. When comparing the outcomes of the interviews with the SOs and those
of the patients, problem areas such as loneliness and lack of self-confidence
were mentioned more often by SOs. Also, more patients were reported to be
repeaters by SOs, and suicidal signals from the patient had been apprehended by
41% of them. Fifty-seven percent of the SOs who had given psychological and/or
practical support to the patient stated it was a burden to them, particularly if
the patient had psychiatric disorders other than adjustment disorders. It was
also found that more than half of the SOs wanted individual counselling and/or
counselling together with the patient. This study stresses the value of co
operation with the SOs after a suicide attempt, both in the immediate assessment
of the patient and in the planning of treatment strategies.
PMID- 10189813
TI - Emotional response of participants to a mental health survey.
AB - Following participation in a mental health survey of 2725 adults aged 18-79,
respondents were asked if the questionnaire had made them feel distressed or
depressed, and if it had been an intrusion on privacy or had made them feel good
about themselves. While 5% reported feeling distressed, 3% depressed and 3% were
concerned about privacy, 35% reported feeling good about themselves. The
participants reporting negative feelings were more likely to be younger women, to
be higher on negative personality measures, to report more anxiety and depression
symptoms, and to have had more childhood adversity and lower social support.
Those who reported positive feelings had higher positive personality scores, more
social support and lower anxiety and depression. This group was more likely to be
older women. Despite the sensitive nature of many of the questions, only a small
percentage of respondents reported distress, while many found that the
questionnaire had made them feel good about themselves. This is important
information to present to Institutional Ethics Committees and to future
participants in such studies.
PMID- 10189814
TI - Fatigue as related to anxiety and depression in a community-based sample of twins
aged over 50.
AB - Measures of fatigue, anxiety and depression were administered in self-report
questionnaire format to a community-based sample of 2703 Australian twins aged
over 50. Factor analysis indicated that a two-factor solution was appropriate and
demonstrated a clear separation between fatigue-related items and questionnaire
items relating to anxiety and depression. Highly congruent factor structures were
derived for male and female subjects.
PMID- 10189815
TI - Psychopathology and attrition in the Baltimore ECA 15-year follow-up 1981-1996.
AB - Predictors of non-response were investigated in a 15-year follow-up (1981-1996)
of 3,481 individuals in a probability sample from the household population of
East Baltimore. Demographics (age, sex, race, education, marital status, and
unemployment), household factors (living arrangements, household income,
household size, and number of children), cultural variables (ancestral ethnicity
and foreign language), social variables (social support and networks, committing
felony, carrying a weapon, using an alias, and wandering), health factors
(physical illness, health insurance, medical assistance, Medicare, receiving
disability benefits, social security, and welfare), interviewer's observation,
and psychopathologic variables (mental disorders, suicide behavior, comorbidity,
and drug use) were collected at baseline in 1981 and in 1982, then linked to
follow-up data between 1993 and 1996. A tracing process involving mail, phone,
criss-cross directories, motor vehicle administration records, a commercial
credit bureau, the state criminal justice system, hospital records, the US
National Death Index, and field tracing were used to locate the original sample.
A total of 3,066 respondents of the original sample (88.1%) were traced. Non
response was categorized into Sample Mortality (that part of the original sample
that died during follow-up), Sample Loss (that part of the original sample that
survived but could not be found) and Refusal (that part of the original sample
that survived and was found but refused to participate). Stratified analysis and
adjusted multiple logistic regression modeling found sample mortality and sample
loss were strongly influenced by individual and household variables and by
psychopathology. Sample mortality was influenced by specific mental disorders or
conditions as mania, drug abuse/dependency, antisocial personality, cognitive
impairment, alcohol abuse/dependency, phobia, drug use (except PCP), and
comorbidity. Household factors protective against mortality include higher
household income, not living as extended members in a married couple family, and
living with children in the household. Persons who were unemployed, widowed or
single, without high school education, male, and 65 years of age or older were
more likely to die. Sample loss was influenced by cognitive impairment,
antisocial personality, and cocaine use. Household factors linked to sample loss
include living in female-headed families, or non-family households, and living
alone. Young nonwhite, divorced/separated, without high school education, and
unemployed were also harder to find. Refusal was associated with being white,
with incomplete elementary education, living as a spouse in traditional married
couple families, or as a child in female-headed families. Psychopathology did not
influence refusal.
PMID- 10189817
TI - Psychiatric hospital care among children and adolescents in Finland: a nationwide
register study.
AB - This register study includes all patients under 18 years in Finland discharged
from psychiatric inpatient treatment in 1990 (n = 818) and 1993 (n = 958). The
prevalence of children and adolescents in the population who had previously been
treated was about 7-8 per 10,000. The incidence of new cases of children and
adolescents who had previously been inpatients within the last year was about 5-6
per 10,000 in this age group. The prevalence was lowest in the preschool group
(about 1:10,000) and highest in the adolescent group (about 12-14:10,000). About
two-thirds of inpatients were boys. Adjustment disorders (DSM-III-R) were the
most common diagnosis both in 1990 and 1993 (about 30%). Mood and anxiety
disorders were the second most frequent (19-23%) and disruptive behaviour
disorders the third most frequent (13-15%) diagnostic category. The diagnostic
profiles differed largely according to sex and age.
PMID- 10189816
TI - The Nordic comparative study on sectorized psychiatry: rates of compulsory care
and use of compulsory admissions during a 1-year follow-up.
AB - BACKGROUND: As part of a Nordic comparative study on contact rates of new
patients and use of services in seven catchment areas, rates of compulsory care
and use of compulsory admissions were explored and analyzed. The total cohort
comprised 2834 patients. RESULTS: A total of 219 patients, 7.7%, were subject to
compulsory care during the follow-up. The proportion of compulsorily admitted
patients of all admitted patients ranged from 6% to 58% in the seven psychiatric
services, and the rate of compulsory care per 1,000 inhabitants, from 0.14 to
0.99. The diagnostic subgroup most commonly committed to inpatient care was
functional psychosis, comprising around 50% of all compulsory admissions. The
strongest predictor of being compulsorily admitted was the specific psychiatric
service the patient was in contact with, followed by having a psychosis
diagnosis. High consumption of care was also associated with compulsory care,
while social variables played only a minor role in predicting compulsory care.
CONCLUSIONS: There was a great variation in rates of compulsory care. No
consistent rural-urban pattern in rates of commitment was found. It is discussed
whether a formal referral procedure to the psychiatric service is associated with
higher rates of compulsory care.
PMID- 10189818
TI - The Psychiatric Care Satisfaction Questionnaire: a reliability and validity
study.
AB - Patient satisfaction can be a useful marker in evaluating the quality of
psychiatric care. However, this form of measurement has been hampered by the lack
of attention paid to the psychometric properties of instruments devised. The
Psychiatric Care Satisfaction Questionnaire (PCSQ) was developed and tests of
acceptability, validity and reliability were undertaken using 52 inpatients.
Content validity was assessed by surveying psychiatrists, other mental health
professionals, MIND workers and patient groups. Thirty-six (67.9%) of all mental
health professionals felt that the questionnaire was a useful measure of
patients' satisfaction with their care, and many comments also suggested high
consensual validity. In terms of content validity, responses from patient groups
indicated that the majority (63.6%) felt it to be a useful measure of patient
satisfaction and 70.5% felt all the areas covered were important. Concurrent and
criterion validity were also good, with high correlations with existing scales
and with those on a section being significantly less satisfied on the PCSQ (F =
13.3, P = 0.0004). Test-retest reliability was adequate (Cohen's kappa 0.48-0.80)
and the internal consistency of the PCSQ was good, at 0.82 (Cronbach's alpha).
The PCSQ performed well in all aspects of validity and reliability, indicating
that it has good psychometric properties and can be a useful tool for measuring
patient satisfaction. However, there remains the need to analyse more closely the
concept of satisfaction and its determinants.
PMID- 10189819
TI - Quality of care for women: where are we now and where are we headed?
PMID- 10189820
TI - Women's perceptions of Medicaid managed care.
PMID- 10189821
TI - The vulnerable transition: puberty and the development of eating pathology and
negative mood.
PMID- 10189822
TI - Gynecologic health consequences to victims of interpersonal violence.
PMID- 10189823
TI - Women's primary care in managed care: clinical and provider issues.
PMID- 10189824
TI - Health plans and purchasers: managing women's primary care.
PMID- 10189825
TI - Managed care and unintended pregnancy: testing the limits of prevention.
PMID- 10189826
TI - Confronting STDs: a challenge for managed care.
PMID- 10189827
TI - Managed care and women's mental health: a focus on depression.
PMID- 10189828
TI - Medicaid managed care: the challenge of providing care to low-income women.
PMID- 10189829
TI - Neither prevention nor cure: managed care for women with chronic conditions.
PMID- 10189830
TI - Quality in women's health: taking the measure of managed care.
PMID- 10189831
TI - Scene and object vision in rats.
AB - Dark Agouti rats learned to discriminate large visual displays ("scenes") in a
computer-controlled Y-maze. Each scene comprised several shapes ("objects")
against a contrasting background. The constant-negative paradigm was used; in
each problem, one constant scene was presented on every trial together with a
trial-unique variable scene, and rats were rewarded for approaching the variable
scene. By varying the manner in which variables differed from the constant, we
investigated what aspects of scenes and the objects comprising them were salient.
In Experiment 1, rats discriminated constant scenes more easily if they contained
four objects rather than six, and they showed a slight attentional bias towards
the lower halves of the screens. That bias disappeared in Experiment 2.
Experiments 3 and 4 showed that rats could discriminate scenes even if the
objects that comprised them were closely matched in position, luminance, and
area. Therefore, they encoded the form of individual objects. Rats perceived
shapes of the same class (e.g. two ellipses) as more similar than shapes from
different classes (e.g. ellipse and polygon) regardless of whether they also
differed in area. This paradigm is suitable for studying the neuropsychology of
perceiving spatial relationships in multi-object scenes and of identifying visual
objects.
PMID- 10189832
TI - Bacterial degradation of immunoglobulin A1 in relation to periodontal diseases.
AB - Periodontal diseases affect millions of people world wide. Prevention and
treatment of these diseases require considerable attention from the individual as
well as society and cause great expenses. Understanding disease etiology and
mechanisms of pathogenesis is a prerequisite for optimal treatment strategies.
The highly variable speed of periodontal destruction and in some sites
persistence for years of deep pockets without further periodontal destruction
points to the significance of individual bacterial species in the complex
subgingival microflora for pathogenesis. Destruction of periodontal tissue occurs
when the load of bacterial virulence factors overcomes the local immune defense.
One way of doing this is by bacterially-induced degradation of IgA which is
considered to mediate its protective functions in an anti-inflammatory way and to
down-regulate inflammation through inhibition of IgG- and IgM-mediated
activities. A competent IgA system may be of particular significance in chronic
inflammatory diseases, as periodontal diseases, where the inflammatory reaction
in itself probably is the main cause of destruction. In these cases, degradation
of IgA may serve the purpose of immune evasion for the bacteria and at the same
time may induce a relatively increased activity in the inflammation-stimulating
part of the immune system which may aggravate periodontal destruction. Both gram
positive rods, streptococci, and Veillonella species from the subgingival
microflora induce an altered immunoelectrophoretic mobility of IgA1 indicative of
removal of terminally positioned sialic acid. Quantitative determination of
residual carbohydrate content of IgA1 after incubation with bacterial cells of
Gram-positive rods has confirmed that they remove sialic acid, and in addition to
that, only minor amounts of carbohydrates. Apart from serving a nutritional
purpose, desialylation of IgA may also serve a purpose of immune evasion.
Glycosylation and, in particular sialic acid protects glycoproteins, including
immunoglobulins, against proteolytic enzymes and deglycosylation of antibodies
increase their sensitivity to proteolytic degradation and inhibit the Fc-mediated
effector functions that mediate antigen disposal. Extensive proteolytic
degradation of IgA1 is induced by a number of bacterial species often associated
with periodontal diseases, including P. gingivalis, Pr. intermedia, and Pr.
nigrescens. These species produce enzymes of broad proteolytic activity, that
also may degrade immunoglobulins of other isotopes, complement factors, iron
containing plasma proteins etc. Extensive hydrolysis of immunoglobulins induced
by these bacteria serve a nutritional purpose and is essential for growth of
other bacteria in mixed cultures. It also has an obvious detrimental effect on
the defence potential of the specific humoral immune system. These bacteria seem
to be essential for the transmissibility of experimental infections in animals
with mixtures of oral bacteria and a likely reason is their ability to provide
the other bacteria with amino acids, peptides, and iron for growth and their
ability to inhibit the immune defence. The hinge region of IgA1 is relatively
resistant to proteolysis because of a high proline content and presence of
several oligosaccharide side chains. It is therefore interesting that a number of
taxonomically unrelated bacteria, including both commensals and overt pathogens,
have evolved the capability to specifically cleave human IgA1 in the hinge
region. These so-called IgA1 proteases leave Fab and Fc fragments intact for
which reason a direct nutritional purpose of the enzymes may be excluded. In the
oral cavity, specific IgA1 proteases are produced by the streptococcal species
that constitute a considerable proportion of initial dental plaque and the flora
on buccal and pharyngeal mucosa. In all three cases the flora is sparse and
contact with saliva, including S-IgA1 antibodies is intimate. (ABSTRACT
TRUNCATED)
PMID- 10189833
TI - Moraxella (Branhamella) catarrhalis: clinical, microbiological and immunological
features in lower respiratory tract infections.
PMID- 10189834
TI - Diagnosis of urogenital Chlamydia trachomatis infection by use of DNA
amplification.
AB - Numerous studies on DNA amplification and diagnosis of C. trachomatis infections
have been performed since the first PCR for detection of C. trachomatis in
clinical samples was described in 1990, but optimal sample preparation procedures
are still lacking. The major problem in evaluating the diagnostic performance of
the DNA amplification methods is that there is no clinical or microbiological
reference standard for C. trachomatis infection. The evaluated diagnostic
performance will therefore always be a reflection of of the chosen comparator(s).
Despite this, it seems that the DNA amplification methods are more sensitive than
the cell culture techniques and the techniques based on immunology. Compared with
the tests based on immunology the specificity is also improved, which makes the
DNA amplification methods useful for sample types contaminated with organisms
cross-reacting in the immunologically based methods, i.e. pharyngeal and rectal
swab samples. However, the specificity and thereby the predictive value of a
positive test is not optimal. Since the predictive value of a positive test is
highly influenced by the prevalence in the tested population, evaluation of
applied tests is constantly needed, especially since the prevalence may be
expected to decrease with intensified test activity and due to changes in safe
sex practices after the advent of AIDS. The improved sensitivity of the DNA
amplification methods allows the use of sample material in which the content of
Chlamydia organisms is lower than in conventional swab samples, i.e. urine,
semen, and vaginal secretions can be used as sample material. these samples can
be obtained by the individuals themselves, and since transport conditions seem
less critical for the test performance, samples can also be taken in the privacy
of the home and subsequently mailed by the individual directly to the diagnostic
laboratory. Such strategy for testing has led to improved partner tracing and
universal screening, compared with traditional swab examinations at physicians'
offices. Tests with an optimal diagnostic performance have not yet been reached,
and several sample categories have not been studied sufficiently. The societal
implications of the use of self-collected samples and universal screening have
not been studied in full, but a milestone for new strategies in detection and
preventing urogenital C. trachomatis epidemics has been reached with the
availability of DNA amplification techniques.
PMID- 10189835
TI - Postantibiotic effect in vitro.
PMID- 10189836
TI - Matrix metalloproteinases in gastrointestinal cancer.
PMID- 10189837
TI - Coeliac disease: how much of what is toxic to whom?
PMID- 10189838
TI - Recognition by human gut gamma delta cells of stress inducible major
histocompatibility molecules on enterocytes.
PMID- 10189839
TI - Systemic and local immune responses against Helicobacter pylori urease in
patients with chronic gastritis: distinct IgA and IgG productive sites.
AB - BACKGROUND: Helicobacter pylori urease is a major target for immune responses
among various bacterial components in H pylori infected patients. AIMS: To
analyse the relation between systemic and local humoral immune responses to H
pylori urease and grades of chronic gastritis. PATIENTS: Seventy five patients
with chronic gastritis associated with H pylori infection were classified into
three groups (grade I, superficial gastritis; II, atrophic gastritis, quiescent;
or III, atrophic gastritis, active). METHODS: Anti-H pylori urease specific
antibodies in the serum, gastric juice, and biopsy specimens were determined by
ELISA or western blotting analysis. The sites for H pylori urease and its
specific antibody producing B lymphocytes were confirmed by immunohistochemical
analysis. RESULTS: In the sera of patients with grade I gastritis, weak IgG but
relatively strong IgG responses to H pylori urease were observed; dominant strong
IgG responses were detected in grade II gastritis. In grade III gastritis,
significant IgG and IgA responses were obtained. A similar pattern of IgA and IgG
responses was detected in gastric juice and tissue. H pylori urease specific,
antibody producing B cells were not found in the gastric mucosa of patients with
grade I gastritis despite the presence of such B cells in the duodenal bulb.
Specific B cells were observed in the gastric mucosa of patients with grade II
and III gastritis with atrophy. CONCLUSIONS: Purified H pylori urease, together
with localisation of its specific antibody producing B cells, are useful for
serological testing and histopathological analysis for determining the stage of
chronic gastritis and studying the pathogenesis of H pylori infection.
PMID- 10189840
TI - The histamine H3 receptor agonist N alpha-methylhistamine produced by
Helicobacter pylori does not alter somatostatin release from cultured rabbit
fundic D-cells.
AB - BACKGROUND: The mechanisms underlying the suppression of somatostatin dependent
reflexes in Helicobacter pylori infection are not fully determined. The H pylori
product N alpha-methylhistamine and inflammatory mediators such as tumour
necrosis factor-alpha (TNF-alpha) may be responsible for the alterations in
somatostatin release. AIMS: To examine the effect of N alpha-methylhistamine on
somatostatin release from cultured somatostatin-secreting D-cells. METHODS:
Rabbit fundic D-cells were obtained by collagenase-EDTA digestion and enriched by
centrifugal elutriation and cultured for 40 hours. The effects of N alpha
methylhistamine on somatostatin release soon after stimulation (two hours) and
after more prolonged exposure (24 hours) were assessed. RESULTS: N alpha
Methylhistamine (1 nM-1 microM) had no effect on basal or carbachol or adrenaline
stimulated release over two hours. Similarly with prolonged exposure no effect on
somatostatin cell content or release was identified. In contrast, TNF-alpha (24
hours) led to a dose dependent fall in both somatostatin content and release.
CONCLUSIONS: N alpha-Methylhistamine had no direct inhibitory effects on D-cells,
but TNF-alpha both significantly reduced the cellular content and inhibited
release. Inflammatory cytokines, rather than N alpha-methylhistamine, are
therefore likely to be responsible for directly inhibiting D-cell function in H
pylori infection.
PMID- 10189841
TI - Analysis of Helicobacter pylori vacA and cagA genotypes and serum antibody
profile in benign and malignant gastroduodenal diseases.
AB - BACKGROUND: Helicobacter pylori species comprise different strains, cytotoxic and
non-cytotoxic, which can be identified on the basis of their genomic pattern.
AIMS: (1) To evaluate the polymorphism of the vacA gene and to ascertain whether
the cagA gene is present in patients with gastric adenocarcinoma. (2) To study
the anti-H pylori antibody profile using western blotting. PATIENTS: Twenty one
patients with gastric adenocarcinoma and 71 with H pylori associated benign
disease (nine gastric ulcer, 29 duodenal ulcer, 25 antral gastritis, and eight
duodenitis). METHODS: The polymerase chain reaction was used to verify the
presence or absence of cagA and to study the polymorphism of vacA in gastric
mucosal samples obtained during endoscopy for patients with benign diseases and
at surgery for patients with gastric adenocarcinoma. Fasting sera were used to
assess anti-H pylori antibodies against different H pylori antigens by western
blotting. RESULTS: CagA gene and the allele s1 of vacA were significantly less
frequent in patients with antral gastritis (60% and 60%) compared with patients
with gastric adenocarcinoma (94% and 100%) and with other non-malignant
gastroduodenal diseases (93% and 87%) (chi 2 = 16.01, p < 0.001; and chi 2 =
13.97, p < 0.01). In patients with gastric adenocarcinoma, antibodies against a
74 kDa H pylori antigen were less frequently found than in patients with benign
diseases. CONCLUSIONS: H pylori infection caused by cagA positive/vacA s1 strains
is a frequent finding in patients with gastric adenocarcinoma. Prospective
studies are needed to confirm whether the low incidence of positive serological
response to the 74 kDa H pylori antigen in patients with gastric adenocarcinoma
is important.
PMID- 10189842
TI - CTLA-4 gene polymorphism is associated with predisposition to coeliac disease.
AB - BACKGROUND: Susceptibility to coeliac disease is strongly associated with
particular HLA class II alleles. However, non-HLA genetic factors are likely to
be required for the development of the disease. Among candidate genes is the CTLA
4 (cytotoxic T lymphocyte associated) gene located on chromosome 2q33 in humans,
which encodes a cell surface molecule providing a negative signal for T cell
activation. AIMS: To investigate CTLA-4 exon 1 polymorphism (position 49 A/G) in
patients with coeliac disease. PATIENTS: 101 patients with coeliac disease and
130 healthy controls. METHODS: Allele specific hybridisation and restriction
enzyme digestion of polymerase chain reaction amplified genomic DNA. RESULTS: The
A allele of the CTLA-4 position 49 polymorphism was found on 82.2% of chromosomes
in patients with coeliac disease compared with 65.8% in controls (p < 0.0001),
mostly in the homozygous form (68.3% in patients versus 47.7% in controls; odds
ratio (OR) 2.36, 95% confidence interval (CI) 1.37 to 4.06, p = 0.002). Four
patients only had the G/G genotype compared with 21 controls (OR 0.21, CI 10.07
to 0.64, p = 0.002). These differences were maintained when subjects were
stratified according to the HLA class II phenotype, in particular when patients
and controls were matched for the presence of the predisposing HLA DQB1*02 (DQ2)
allele or HLA-DQA1*0501/DQB1*02 heterodimer. CONCLUSION: The CTLA-4 gene
polymorphism is a non-HLA determinant that predisposes to coeliac disease.
Whether it directly contributes to disease susceptibility or represents a marker
for a locus in linkage disequilibrium with CTLA-4 needs further investigation.
PMID- 10189843
TI - Measurement of gluten using a monoclonal antibody to a coeliac toxic peptide of A
gliadin.
AB - BACKGROUND: Future European Community regulations will require a sensitive and
specific assay for measurement of coeliac toxic gluten proteins in foods marketed
as gluten-free. To avoid spurious cross reactions with non-toxic proteins,
specific antibodies and target antigens are required. A synthetic 19 amino acid
peptide of A gliadin has been shown to cause deterioration in the morphology of
small intestinal biopsy specimens of coeliac patients in remission. AIMS: To
develop an assay for detection of gluten in foods, based on measurement of a
known toxic peptide. METHODS: A monoclonal antibody raised against the toxic A
gliadin peptide, with a polyclonal anti-unfractionated gliadin capture antibody,
was used to develop a double sandwich enzyme linked immunosorbent assay (ELISA)
for the measurement of gluten in foods. RESULTS: Standard curves for gliadin and
for rye, barley, and oat prolamins were produced. The sensitivity of the assay
was 4 ng/ml of gliadin, 500 ng/ml for rye prolamins, and 1000 ng/ml for oat and
barley prolamins. The assay could detect gluten in cooked foods, although at
reduced sensitivity. Prolamins from coeliac non-toxic rice, maize, millet, and
sorghum did not cross react in the assay. A variety of commercially available
gluten-free foods were analysed; small quantities of gluten were detected in some
products. CONCLUSION: The assay may form the basis of a sensitive method for
measurement of gluten in foods for consumption by patients with coeliac disease.
PMID- 10189844
TI - Bromelain protects piglets from diarrhoea caused by oral challenge with K88
positive enterotoxigenic Escherichia coli.
AB - BACKGROUND: K88 positive enterotoxigenic Escherichia coli (K88+ ETEC) is an
important cause of diarrhoea in young piglets. K88+ ETEC pathogenesis relies on
attachment to specific glycoprotein receptors located on the intestinal mucosa.
Proteolytic treatment of these receptors in vitro and in vivo prevents attachment
of K88+ ETEC to piglet small intestines and may be of clinical use to prevent
K88+ ETEC pathogenesis. AIMS: To determine whether bromelain, a proteolytic
extract obtained from pineapple stems, would protect piglets against K88+ ETEC
diarrhoea and to confirm and extend earlier findings on the effects of bromelain
on K88+ ETEC receptors in vivo. METHODS: Bromelain (0, 12.5, or 125 mg) was
orally administered to just weaned piglets for 10 days. One day following
commencement of bromelain treatment, piglets were challenged with K88+ ETEC (5 x
10(10) K88ac:0149) for seven days. Intestinal contents from unchallenged piglets
were obtained via an intestinal fistula, and tested for their ability to bind
K88+ ETEC before and after bromelain treatment. RESULTS: Both doses of bromelain
were successful in reducing the incidence of K88+ ETEC diarrhoea and protected
piglets from life threatening disease. Bromelain treated pigs also had
significantly increased weight gain compared with untreated pigs. Bromelain only
temporarily inhibited K88+ ETEC receptor activity, with receptor activity being
regenerated 30 hours following treatment, consistent with the regeneration of new
enterocytes. CONCLUSION: Results show that bromelain can temporarily inactivate
ETEC receptors in vivo and protect against ETEC induced diarrhoea. Bromelain may
therefore be an effective prophylaxis against ETEC infection.
PMID- 10189845
TI - Secretion imbalance between tumour necrosis factor and its inhibitor in
inflammatory bowel disease.
AB - BACKGROUND: Tumour necrosis factor (TNF) alpha and TNF-beta are soluble ligands
binding to TNF receptors with similar activities; soluble TNF receptors
neutralise TNF activity by acting as inhibitors. Little is known about the
cytokine/soluble receptor role in inflammatory bowel disease (IBD). AIMS: To test
the hypothesis that an imbalance in secretion between TNF and TNF inhibitors
plays a role in gut inflammation in patients with IBD. METHODS: The secretion of
TNF-alpha, TNF-beta, and soluble TNF receptors was compared in the culture
supernatants of colonic biopsy specimens and isolated lamina propria mononuclear
cells from patients with active colonic IBD. RESULTS: Spontaneous secretion of
TNF-alpha in involved IBD mucosa was higher than in normal control and self
limited colitis mucosa. Secretion of TNF-beta was higher in patients with Crohn's
disease than in those with ulcerative colitis. Soluble TNF receptor in IBD mucosa
inhibited TNF activity. Type 2 soluble receptor release from IBD mucosa was
increased in active inflammation; release from lamina propria cells was not
increased. Mucosal TNF-alpha production correlated with severity of disease.
CONCLUSIONS: Results showed enhanced secretion of TNF-alpha but failure to
release enhanced amounts of soluble TNF receptor in lamina propria mononuclear
cells of patients with IBD. An imbalance in secretion between TNF and TNF
inhibitor may be implicated in the pathogenesis of IBD.
PMID- 10189846
TI - Analysis of MHC class II DP, DQ and DR alleles in Crohn's disease.
AB - BACKGROUND: Although inflammation in Crohn's disease is believed to be mediated
by activated T cells, genotyping of all MHC class II alleles in white people with
this disease has not been reported. AIMS: To perform a detailed molecular
analysis of HLA DPB, DQB, and DRB genes in white patients with Crohn's disease
and controls in order to determine if the inheritance of any class II genes
confers susceptibility or resistance to this disease. METHODS: Complete molecular
typing of HLA class II DPB, DQB, and DRB alleles was performed in 58 white
patients with Crohn's disease and 93 healthy controls using a polymerase chain
reaction-sequence specific oligonucleotide based approach. RESULTS: No
significant association with any DPB or DQB alleles was noted in patients with
Crohn's disease. Since our previous studies had shown a strong association of an
HLA DRB3*0301/DRB1*1302 haplotype with Crohn's disease, we re-examined this
association using more stringent genotyping criteria. This haplotype was present
in 20.7% of patients and 5.4% of controls (p = 0.0066; relative risk = 4.59).
CONCLUSIONS: The DRB3*0301/DRB1*1302 haplotype is the only significant MHC class
II association noted in white people with Crohn's disease and represents the
strongest association of any MHC or non-MHC locus with this disease.
PMID- 10189847
TI - Impact of endoscopic biopsy surveillance of Barrett's oesophagus on pathological
stage and clinical outcome of Barrett's carcinoma.
AB - BACKGROUND: The efficacy of endoscopic biopsy surveillance of Barrett's
oesophagus in reducing mortality from oesophageal cancer has not been confirmed.
AIMS: To investigate the impact of endoscopic biopsy surveillance on pathological
stage and clinical outcome of Barrett's carcinoma. METHODS: A clinicopathological
comparison was made between patients who initially presented with oesophageal
adenocarcinoma (n = 54), and those in whom the cancer had been detected during
surveillance of Barrett's oesophagus (n = 16). RESULTS: The surveyed patients
were known to have Barrett's oesophagus for a median period of 42 months (range 6
144 months). Prior to the detection of adenocarcinoma or high grade dysplasia, 13
to 16 patients (81%) were previously found to have low grade dysplasia. Surgical
pathology showed that surveyed patients had significantly earlier stages than non
surveyed patients (p = 0.0001). Only one surveyed patient (6%) versus 34 non
surveyed patients (63%) had nodal involvement (p = 0.0001). Two year survival was
85.9% for surveyed patients and 43.3% for non-surveyed patients (p = 0.0029).
CONCLUSIONS: The temporal course of histological progression in our surveyed
patients supports the theory that adenocarcinoma in Barrett's oesophagus develops
through stages of increasing severity of dysplasia. Endoscopic biopsy
surveillance of Barrett's oesophagus permits detection of malignancy at an early
and curable stage, thereby potentially reducing mortality from oesophageal
adenocarcinoma.
PMID- 10189848
TI - Clinical symptoms, hormone profiles, treatment, and prognosis in patients with
gastric carcinoids.
AB - BACKGROUND: Type 1 gastric carcinoids are associated with hypergastrinaemia and
chronic atrophic gastritis, type 2 occur in patients with multiple endocrine
neoplasia type 1 combined with Zollinger-Ellison syndrome, and type 3 lack any
relation to hypergastrinaemia. Type 1 tumours are usually benign whereas type 3
are highly malignant. AIMS: To identify possible tumour markers in patients with
gastric carcinoids. PATIENTS/METHOD: Nine patients with type 1, one with type 2,
and five with type 3 were evaluated with regard to symptoms, hormone profile, and
prognosis. RESULTS: Plasma chromogranin A was increased in all patients but was
higher (p < 0.01) in those with type 3 than those with type 1 carcinoids. All
patients with type 3 carcinoids died from metastatic disease, but none of the
type 1 patients died as a result of their tumours. One type 1 patient with a
solitary liver metastasis received interferon alpha and octreotide treatment.
Nine months later, the metastasis was no longer detectable. She is still alive
eight years after diagnosis, without recurrent disease. This represents the only
reported case of foregut carcinoid with an unresectable liver metastasis that
seems to be have been cured by biotherapy. CONCLUSIONS: Plasma chromogranin A
appears to be a valuable tumour marker for all types of gastric carcinoid.
Combination therapy with interferon alpha and octreotide may be beneficial in
patients with metastasising type 1 gastric carcinoids.
PMID- 10189849
TI - Flat adenomas exist in asymptomatic people: important implications for colorectal
cancer screening programmes.
AB - BACKGROUND: Flat adenomas are non-exophytic with a flat top or central depression
and histologically the depth of dysplastic tissue is never more than twice the
mucosal thickness. Flat adenomas frequently contain severely dysplastic tissue,
and may progress rapidly through the adenoma-carcinoma sequence. Flat lesions
have never been described in a British asymptomatic population. AIMS: To
determine whether flat adenomas exist in an asymptomatic population participating
in a large randomised controlled trial of flexible sigmoidoscopy screening.
PATIENTS: A total of 3000 subjects (aged 55-64 years) underwent screening by
flexible sigmoidoscopy. METHODS: All polyps were removed and sent for histology.
The number of polyps with endoscopic and histological features of flat adenomas
was recorded. RESULTS: Three subjects had a total of four flat lesions--that is,
one per 1000 people screened. Three contained severely dysplastic tissue, one a
focus of adenocarcinoma. Three of the four lesions were less than 5 mm in size
and the fourth was 15 mm in diameter. CONCLUSIONS: Flat lesions with severe
dysplasia exist in the asymptomatic population. This has major implications for
gastroenterologists who should be trained to identify them. Their existence is of
importance to molecular biologists and epidemiologists investigating the
aetiology of colorectal cancer.
PMID- 10189850
TI - A monoclonal anti-interleukin 8 antibody (WS-4) inhibits cytokine response and
acute lung injury in experimental severe acute necrotising pancreatitis in
rabbits.
AB - BACKGROUND: Interleukin 8 (IL-8) has recently been proposed to have an important
role in mediating the development of the systemic sequelae associated with severe
acute pancreatitis. AIMS: To define the role of IL-8 in acute pancreatitis by
neutralising its effects with a monoclonal anti-IL-8 antibody (WS-4), in a rabbit
model of severe acute pancreatitis. METHODS: Acute pancreatitis was induced by
retrograde injection of 5% chenodeoxycholic acid into the pancreatic duct and
duct ligation. Twenty rabbits were divided equally into two groups: acute
pancreatitis controls received physiological saline and the treated group
received WS-4, 30 minutes before induction of acute pancreatitis. RESULTS:
Pretreatment of animals with WS-4 resulted in significant down regulation of
serum IL-8 and tumour necrosis factor alpha (TNF-alpha) from three to six hours
after induction of acute pancreatitis (p = 0.011 and 0.047 for IL-8 and 0.033 and
0.022 for TNF-alpha, respectively). In addition, a significant reduction in the
CD11b and CD18 positive cells and the amount of interstitial neutrophil
infiltration in the lungs from WS-4 treated animals was seen. In contrast, WS-4
did not alter the amount of pancreatic necrosis and the serum concentrations of
amylase, lipase, calcium, and glucose. CONCLUSION: WS-4 cannot change the amount
of pancreatic necrosis induced by injection of 5% bile acid, but does reduce the
acute lung injury, presumably through inhibition of circulating IL-8 and TNF
alpha, and CD11b/CD18 in lung tissue. Therefore, a role of IL-8 in the
progression of acute pancreatitis and the development of its systemic
complications is suggested.
PMID- 10189851
TI - Distribution and metabolism of intravenously administered trefoil factor
2/porcine spasmolytic polypeptide in the rat.
AB - BACKGROUND: Trefoil peptides are secreted by mucus producing cells in the
gastrointestinal tract and are supposed to be involved in oligomerisation
processes of the mucin glycoproteins in the lumen. Endocrine functions have also
been suggested. AIMS: To target possible binding sites for iodine-125 labelled
porcine spasmolytic polypeptide (pSP) in an in vivo rat model. METHODS: 125I-pSP
was given by intravenous injection to female Sprague-Dawley rats. The
distribution of 125I-pSP was assessed by gamma counting of samples of organs and
by autoradiography of paraffin wax embedded sections. The degradation of 125I-pSP
was studied by trichloroacetic acid precipitation, and the saturability of
binding by administration of excess unlabelled peptide. RESULTS: 125I-pSP was
taken up in the kidneys and the gastrointestinal tract and was excreted almost
unmetabolised in the urine. In the stomach, it could be displaced by unlabelled
pSP in a dose dependent manner. Autoradiography showed grains in mucous neck
cells, parietal cells, the mucus layer, and the pyloric glands of the stomach; in
Brunner's glands and the Paneth cells in the small intestine; and in cells in the
lower part of the crypts in the colon. CONCLUSIONS: 125I-pSP from the circulatory
system is taken up by mucus producing cells in the gastrointestinal tract. The
binding can be displaced by non-radioactive pSP, suggesting the presence of a
receptor.
PMID- 10189852
TI - Evidence for a lipid specific effect in nutrient induced human proximal gastric
relaxation.
AB - BACKGROUND/AIM: The presence of lipid in the upper gut is able to modify
gastrointestinal motor performance, but its influence on the relaxation of the
human stomach, which is known to modify gastric emptying, remains incompletely
understood. The relaxation of the proximal stomach in response to various lipid
concentrations was therefore studied in healthy volunteers. Since the observed
effects could be mediated through osmolality or energy sensitive pathways, the
effects of equicaloric and equiosmolar non-lipid solutions were also determined.
METHODS: The tone of the proximal stomach was measured during stepwise inflation
of a non-compliant bag sited in the proximal stomach, both before and after a
test meal was delivered intragastrically. Iso-osmolar lipid emulsions were
diluted in iso-osmolar saline at concentrations of 1.25, 2.5, 5, 10, and 20%.
NaCl solutions at osmolalities of 300, 600, 1200 and 2400 mmol/kg and glucose
solutions of 836 and 3344 kJ/l were also given. RESULTS: All lipid meals of 2.5%
or greater concentration induced a reduction in gastric tone in a non-dose
dependent manner, responses to 5% lipid (median (range) 74 (62-92)%) being
similar to those to 20% lipid (80 (55-83)%; p > 0.05). No relaxation was elicited
by isocaloric glucose. NaCl only consistently caused relaxation at 2400 mmol/kg.
CONCLUSION: Lipid meals reduce human proximal gastric tone by a lipid specific
mechanism, independently of their energy content or osmolality.
PMID- 10189853
TI - Intraluminal capsaicin does not affect fluid and electrolyte absorption in the
human jejunum but does cause pain.
AB - BACKGROUND: Stimulation of sensory nerves with capsaicin regulates ion transport
in the small intestine in animal experiments. AIM: To investigate whether sensory
nerves that are stimulated by capsaicin administration influence fluid and
electrolyte absorption in the human jejunum in vivo. METHOD: Intestinal perfusion
studies were performed in 12 healthy subjects using a four lumen tube with a
proximal occlusion balloon and a plasma-like electrolyte solution. After an
initial control period, 5 (n = 3), 10 (n = 8), or 50 (n = 1) micrograms/ml
capsaicin was added to the perfusate, and this was followed by a final control
period. Rates of absorption of water, sodium, potassium, chloride, and
bicarbonate were determined in a 30 cm segment of jejunum using a non-absorbable
volume marker. RESULTS: At all three concentrations of capsaicin there were no
significant changes in water and electrolyte absorption as compared with control
periods. Two subjects who received 10 micrograms/ml and the subject receiving 50
micrograms/ml experienced crampy abdominal pain. CONCLUSION: The results do not
support the hypothesis that capsaicin sensitive afferent nerves are involved in
the physiological regulation of net absorption or secretion across the human
jejunal mucosa. Chemical stimulation of these nerves, however, gives rise to
abdominal pain.
PMID- 10189854
TI - Level of chronic life stress predicts clinical outcome in irritable bowel
syndrome.
AB - BACKGROUND: Life stress contributes to symptom onset and exacerbation in the
majority of patients with irritable bowel syndrome (IBS) and functional dyspepsia
(FD); research evidence is conflicting, however, as to the strength of these
effects. AIMS: To test prospectively the relation of chronic life stress threat
to subsequent symptom intensity over time. PATIENTS: One hundred and seventeen
consecutive outpatients satisfying the modified Rome criteria for IBS (66% with
one or more concurrent FD syndromes) participated. METHODS: The life stress and
symptom intensity measures were determined from interview data collected
independently at entry, and at six and 16 months; these measures assessed the
potency of chronic life stress threat during the prior six months or more, and
the severity and frequency of IBS and FD symptoms during the following two weeks.
RESULTS: Chronic life stress threat was a powerful predictor of subsequent
symptom intensity, explaining 97% of the variance on this measure over 16 months.
No patient exposed to even one chronic highly threatening stressor improved
clinically (by 50%) over the 16 months; all patients who improved did so in the
absence of such a stressor. CONCLUSION: The level of chronic life stress threat
predicts the clinical outcome in most patients with IBS/FD.
PMID- 10189855
TI - Heterozygotes for HFE mutations have no increased risk of advanced alcoholic
liver disease.
AB - BACKGROUND: Iron overload is common in the livers of alcoholics and may play a
role in disease pathogenesis. An MHC like gene, HFE, has recently been identified
that is mutated in most patients with hereditary haemochromatosis (C282Y in 90%
and H63D in 45% of the remainder). AIM: To examine the hypothesis that these
mutations determine hepatic iron status in alcoholics and play a role in pre
disposition to advanced alcoholic liver disease. METHODS: The HFE gene was
genotyped in 257 patients with alcoholic liver disease and 117 locally matched
healthy volunteers. In addition, iron staining was scored (0-4) on biopsy
specimens from fibrotic/cirrhotic patients with and without HFE mutations matched
for age and sex. RESULTS: Some 15.7% of fibrotic/cirrhotic patients were C282Y
heterozygotes compared with 13.7% of controls (p = 0.77). One control and three
patients were C282Y homozygotes. Of chromosomes without the C282Y mutation,
68/442 (15.4%) of patients' chromosomes carried the H63D mutation compared with
36/216 (16.6%) of control chromosomes (p = 0.91). Significant (> grade 1)
hepatocyte iron staining was seen in 6/23 C282Y heterozygotes and 4/26 H63D
heterozygotes compared with 4/23 controls. CONCLUSIONS: Possession of a single
copy of either of the two HFE mutations influences neither liver iron content nor
the risk of fibrotic disease in alcoholics.
PMID- 10189856
TI - Thrombelastographic changes and early rebleeding in cirrhotic patients with
variceal bleeding.
AB - BACKGROUND: Routine coagulation tests do not necessarily reflect haemostasis in
vivo in cirrhotic patients, particularly those who have bleeding varices.
Thrombelastography (TEG) can provide a global assessment of haemostatic function
from initial clot formation to clot dissolution. AIM: To evaluate TEG changes in
cirrhotic patients with variceal bleeding and their association with early
rebleeding. PATIENTS/METHODS: Twenty cirrhotic patients with active variceal
bleeding had serial TEG and routine coagulation tests daily for seven days. The
TEG variables before the day of rebleeding (n = 6) were compared with those of
patients without rebleeding (n = 14). RESULTS: Baseline characteristics of the
rebleeding and non-rebleeding groups were comparable apart from a higher
incidence of uncontrolled infection on the day of rebleeding in the rebleeding
group (p = 0.007). The patients in the rebleeding group were more hypocoagulable
before the day of rebleeding as shown by longer r (42 v 24 mm, p < 0.001) and k
(48 v 13 mm, p < 0.001) and smaller a (12 v 38 degrees, p < 0.001) compared with
the mean of daily results of the non-rebleeding group. Routine coagulation tests,
however, showed no significant differences between the two groups. CONCLUSION:
The results of serial TEG measurements suggest that hypocoagulability may be
associated with early rebleeding in cirrhotic patients.
PMID- 10189857
TI - Hepatosplanchnic haemodynamics and renal blood flow and function in rats with
liver failure.
AB - BACKGROUND: Massive liver necrosis, characteristic of acute liver failure, may
affect hepatosplanchnic haemodynamics, and contribute to the alterations in renal
haemodynamics and function. AIMS: To investigate the relation between
hepatosplanchnic haemodynamics, including portal systemic shunting, and renal
blood flow and function in rats with acute liver failure. METHODS: Liver failure
was induced in male Wistar rats by intraperitoneal injection of 1.1 g/kg of D(+)
galactosamine hydrochloride. The parameters assessed included; systemic,
hepatosplanchnic, and renal blood flow (57Co microsphere method); portal-systemic
shunting and intrarenal shunting (consecutive intrasplenic, intraportal, or renal
arterial injections of 99mTc methylene diphosphonate and 99mTc albumin
microspheres); arterial blood pressure and portal pressure; renal function; and
liver function (liver function tests and 14C aminopyrine breath test). RESULTS:
Progressive liver dysfunction was accompanied by the development of a
hyperdynamic circulation, a highly significant decrease in renal blood flow and
function, and an increase in intrarenal shunting 36, 42, and 48 hours after
administration of D-galactosamine. The alterations in renal blood flow and
function were accompanied by significant increases in portal pressure, portal
venous inflow, and intrahepatic portal systemic shunting in galactosamine treated
rats compared with controls. There was a significant correlation between changes
in renal blood flow and changes in portal pressure, intrahepatic portal systemic
shunting, and deterioration in liver function (r = 0.8, p < 0.0001). CONCLUSIONS:
The results of this study suggest that both increased intrahepatic portal
systemic shunting and hepatocyte impairment may contribute to alterations in
renal haemodynamics and function.
PMID- 10189858
TI - Two way push videoenteroscopy in investigation of small bowel disease.
AB - AIMS: To evaluate the diagnostic yield and safety of a new push type
videoenteroscope (PVE) for diagnosis of small bowel disease. METHODS: Three
hundred and thirteen patients were referred for one or two way PVE from December
1993 to June 1996. Indications for PVE were: an unexplained iron deficiency
anaemia with or without clinically evident gastrointestinal bleeding; or a
complementary investigation for suspected small bowel disease, after a small
bowel barium follow through (SBBFT) considered as normal or abnormal, but without
a definite diagnosis. RESULTS: A jejunoscopy and a retrograde ileoscopy were
carried out in 306 and 234 patients, respectively. In patients with isolated
anaemia (n = 131) and those with clinically evident gastrointestinal bleeding
associated anaemia (n = 72), PVE provided a diagnosis in 26 (19.8%) and 22
(30.5%) cases, respectively. Lesions found were located in the jejunoileum in 30
(14.7%) patients and in the gastroduodenum or the colon in 18 (8.8%) patients-
that is, within the reach of the conventional gastroscope/colonoscope. In
patients with normal (n = 54) or abnormal (n = 56) SBBFT, PVE provided a
diagnosis in 17 (31%) and 27 (48%) cases, respectively. In 25% of cases, the
abnormal appearance of SBBFT was not confirmed. The site of the radiological
abnormality was not reached in 27% of cases. Lesions were located at the jejunum
and the ileum in 59 (64%) and 33 (36%) cases, respectively. CONCLUSIONS: PVE is
useful in around 30% of cases of unexplained anaemia or after an SBBFT which
failed to provide an accurate aetiological diagnosis. Use of retrograde
videoenteroscopy increases diagnostic yield by one third.
PMID- 10189859
TI - Ischaemic enterocolitis complicating idiopathic dysautonomia.
AB - A previously fit 23 year old adult male who presented with a sudden onset of
profound autonomic neuropathy, for which no cause could be found, is described.
The patient subsequently developed ischaemic enterocolitis that ultimately
necessitated colectomy and subtotal enterectomy. Potential neural and humoral
mechanisms are discussed.
PMID- 10189860
TI - Gastroenterology research in the United Kingdom: funding sources and impact.
AB - AIMS: To determine the sources of founding for UK gastroenterology research
papers and the relative impact of papers funded by different groups and of
unfunded ones. METHODS: UK gastroenterology papers from 1988-94 were selectively
retrieved from the Science Citation Index by means of a specially constructed
filter based on their title keywords and journal names. They were looked up in
libraries to determine their funding sources and these, together with their
numbers of authors, numbers of addresses, and research category (clinical/basic)
were considered as input parameters to the research. Output parameters analysed
were mean journal impact category, citation counts by papers, and the frequency
of citation by a US patient. RESULTS: Gastroenterology papers comprise about 7%
of all UK biomedical research and 46% of them have no acknowledged funding
source. One quarter of the papers acknowledged government support, and a similar
fraction a private, non-profit source; 11% were funded by the pharmaceutical
industry. The papers acknowledging funding had significantly more impact than the
others on all three measures. The citing patents had six times more UK inventors
than the average for all US Patent and Trademark Office patents in the relevant
classes and were mostly generic in application. CONCLUSION: The variation in
impact of papers funded by different sources can mostly be explained by a simple
model based on the input factors (numbers of funding bodies, numbers of authors,
numbers of addresses, and research type). The national science base in
gastroenterology is important for the underpinning of UK invented patents citing
to it.
PMID- 10189861
TI - Salt and water absorption in the human colon: a modern appraisal.
PMID- 10189862
TI - Co-screening for primary biliary cirrhosis and coeliac disease. Association
between primary biliary cirrhosis and coeliac disease.
PMID- 10189863
TI - Co-screening for primary biliary cirrhosis and coeliac disease. Primary biliary
cirrhosis and coeliac disease: a study of relative prevalences.
PMID- 10189864
TI - Co-screening for primary biliary cirrhosis and coeliac disease. Helicobacter
pylori: the African enigma.
PMID- 10189866
TI - Joint meeting of the European Brain and Behaviour Society and the Israel Center
for Psychobiology. Introductory remarks.
PMID- 10189865
TI - Co-screening for primary biliary cirrhosis and coeliac disease. 6-Mercaptopurine
metabolism in Crohn's disease.
PMID- 10189867
TI - Serotonin: a behaviorally active compound in the caudate nucleus of cats.
PMID- 10189868
TI - Behavioral and biochemical effects of L-DOPA in cats.
PMID- 10189869
TI - Effect of clozapine and some other antipsychotic agents on synthesis and turnover
of dopamine formed from 14C-tyrosine in mouse brain.
PMID- 10189870
TI - Central excitatory effects of delta 1- and delta 6-tetrahydrocannabinol.
PMID- 10189871
TI - Cerebral seizure susceptibility and patterns of paroxysmal activity during
embryonic development in the domestic chicken.
PMID- 10189872
TI - gamma-Hydroxybutyric acid, imidazoleacetic acid, cerebral metabolism and induced
sleep.
PMID- 10189873
TI - Technique for producing an alcohol withdrawal syndrome in rats.
PMID- 10189874
TI - Drugs which can induce earlier roosting in the self-selected circadian rhythm of
the canary.
PMID- 10189875
TI - Split-brain behavior without splitting. Tactile discriminations in monkeys.
PMID- 10189876
TI - Sensory input competition in the visual fields and cerebral dominance.
PMID- 10189877
TI - Absence of effect of caudate lesions on delayed responses acquired after large
frontal ablations in cats.
PMID- 10189878
TI - The prevention of long-term memory formation by the intracisternal administration
of 2,6-diaminopurine, a reversible inhibitor of RNA synthesis.
PMID- 10189879
TI - Effects of corticosteroids on hypothalamic adrenocortical regulation, on
responses to neural stimuli and the pathways involved.
PMID- 10189880
TI - Photoreceptor transduction. A new system.
PMID- 10189881
TI - Retrograde amnesia in normal subjects, amnesic patients and patients with
unilateral cerebral lesions.
PMID- 10189882
TI - Association between smoking and tumor progression in Japanese women with
adenocarcinoma of the lung.
AB - We studied the effect of smoking on tumor progression in 3312 patients with lung
cancer registered at the National Matsudo Hospital and National Cancer Center
Hospital East between 1977 and 1996. The odds ratios of the following variables
for tumor extent (localized versus advanced disease) and hazard ratios for
survival were calculated in both sexes separately using the logistic regression
and Cox proportional hazard models, respectively: smoking history, number of
cigarettes smoked per day, pack-years smoked, age, histological type, and the
year of admission. Of the 943 women, 367 (38.9%) were smokers and 694 (73.6%) had
adenocarcinoma, whereas of the 2369 men, 2255 (95.2%) were smokers and 1010
(42.6%) had adenocarcinoma. In female adenocarcinoma patients, the odds ratio
(95% confidence interval) for advanced disease and the hazard ratio (95%
confidence interval) for survival with an increase of 30 cigarettes smoked per
day were 2.86 (1.49-5.49) and 1.52 (1.13-2.04), respectively, but in those with
non-adenocarcinoma, the odds ratio and hazard ratio were 0.96 (0.41-2.23) and
1.13 (0.75-1.70), respectively. In male patients, smoking history influenced
tumor progression regardless of histological type, but the odds ratios and hazard
ratios were lower than those for women with adenocarcinoma. In conclusion,
smoking habit was closely correlated with progression of adenocarcinoma in women.
This association was not observed in women with non-adenocarcinoma and was weaker
in men, suggesting various effects of smoking on lung cancer development
depending on gender and the histological type of the tumor.
PMID- 10189883
TI - Tea polyphenol intake and changes in serum pepsinogen levels.
AB - Following a phase I study, a phase II study was conducted to evaluate the effects
of two different doses of tea polyphenols on serum pepsinogen levels. Subjects
were patients aged 40 to 69 years who had undergone gastroscopy between 1995 and
1997 at Aichi Cancer Center Hospital, and had been found to have no disease
requiring medication. Those with pepsinogen I < 70 ng/ml and pepsinogen I/II
ratio < 6 were included in this study. Capsules containing 100 mg of tea
polyphenols were administered for 1 year: 1 capsule per day for 101 patients (42
males and 59 females), and 6 capsules (equivalent to 10 cups) per day for 83
patients (30 males and 53 females). The enrollment of the 1 capsule group
preceded that of the 6 capsule group, in which re-participation was allowed.
Blood samples were obtained 1 year after participation from 86 participants of
the 1 capsule group and 77 participants (43 new participants and 34 re
participants) of the 6 capsule group. The compliance in polyphenol capsule intake
ranged from 11.4 to 105.7% (87.6% on average) of the scheduled amount for the 1
capsule group and 3.2 to 112.3% (77.8% on average) for the 6 capsule group. No
serious polyphenol-related adverse effects were reported. The difference in
pepsinogen I between before and after 1 year intake of the polyphenol was 3.1
ng/ml for the 43 participants of the 6 capsule group, but 3.5 ng/ml for the 1
capsule group. The mean pepsinogen I/II ratio for the 43 participants increased
from 2.37 by 0.08. This increase was not larger than that for the 1 capsule group
(from 2.61 by 0.11). Among 34 participants in both interventions, no significant
increase in pepsinogen I and I/II ratio for the 6 capsule intervention was
observed. This result suggests that additional polyphenol intake for 1 year in
Japanese does not improve pepsinogen levels, which are considered to reflect
stomach atrophy, a high-risk condition for stomach cancer.
PMID- 10189885
TI - Inhibition by beta-carotene of upper respiratory tumorigenesis in hamsters
receiving diethylnitrosamine followed by cigarette smoke exposure.
AB - In recent intervention studies, beta-carotene failed to reduce or even increased
the incidence of lung cancers in smokers. In the present investigation, the
modifying effects of beta-carotene at various doses on the development of upper
respiratory tract tumors were investigated in Syrian hamsters treated with
diethylnitrosamine (DEN) and cigarette smoke. A total of 120 male 5-week-old
hamsters were divided into 4 groups, each consisting of 30 animals. After a
single subcutaneous (s.c.) injection of 100 mg/kg DEN, hamsters in groups 1-4
were respectively administered diets supplemented with beta-carotene at doses of
0.5%, 0.05%, 0.005% or 0% during experimental weeks 1 to 13, and simultaneously
exposed to cigarette smoke. The duration of cigarette smoke exposure was 9 min
twice a day, 5 days a week. Because of a marked reduction of body weight in group
1, the highest dose of beta-carotene was changed to 0.25% after 10 days. In all
groups, epithelial hyperplasias and/or papillomas were induced in the larynx and
trachea. However, the incidence and multiplicity of papillomas in group 1 were
significantly (P < 0.05) lower than the group 4 values. Moreover, the beta
carotene treatments significantly (P < 0.05 or 0.01) reduced both the incidence
and multiplicity of hyperplasias in a dose-dependent manner. The levels of
retinol and beta-carotene in the serum, and the retinol level in the liver, were
also elevated with dose dependence. Our results thus indicate that beta-carotene
inhibits tumorigenesis, even at the high dose of 0.25%, under the present
experimental conditions.
PMID- 10189884
TI - Urinary bladder lesions after the Chernobyl accident: immunohistochemical
assessment of p53, proliferating cell nuclear antigen, cyclin D1 and
p21WAF1/Cip1.
AB - During the 11-year period subsequent to the Chernobyl accident, the incidence of
urinary bladder cancer in Ukraine has increased from 26.2 to 36.1 per 100,000
population. Cesium-137 (137Cs) accounts for 80-90% of the incorporated
radioactivity in this population, which has been exposed to long-term, low-dose
ionizing radiation, and 80% of the more labile pool of cesium is excreted via the
urine. The present study was performed to evaluate the histopathological features
and the immunohistochemical status of p53, p21WAF1/Cip1, cyclin D1 and PCNA
(proliferating cell nuclear antigen) in urinary bladder mucosa of 55 males (49-92
years old) with benign prostatic hyperplasia who underwent surgery in Kiev,
Ukraine, in 1995 and 1996. Group I (28 patients) inhabiting radiocontaminated
areas of the country, group II (17 patients) from Kiev city with less
radiocontamination and a control group III (10 patients) living in so-called
"clean" areas of Ukraine were compared. In groups I and II, an increase in
multiple areas of moderate or severe dysplasia or carcinoma in situ was seen in
42 (93%) of 45 cases. In addition, two small transitional cell carcinomas were
found in one patient in each of groups I and II. Nuclear accumulation of p53,
PCNA, cyclin D1, and to a lesser extent p21WAF1/Cip1, was significantly increased
in both groups I and II as compared with the control group III, indicating
possible transformation events or enhancement of repair activities, that may
precede the defect in the regulatory pathway itself, at least in the G1 phase of
the cell cycle. Our results suggest that early malignant transformation is taking
place in the bladder urothelium of people in the radiocontaminated areas of
Ukraine and that this could possibly lead sometime in the future to an increased
incidence of urinary bladder cancer.
PMID- 10189886
TI - Effects of continuous hepatitis with persistent hepatitis C viremia on outcome
after resection of hepatocellular carcinoma.
AB - The effect of persistent hepatitis C viremia on the outcome after resection of
hepatocellular carcinoma (HCC) was investigated in 59 consecutive patients with a
single small HCC (< or = 3.0 cm in diameter). The presence of serum hepatitis C
virus (HCV) RNA was evaluated using a reverse transcription polymerase chain
reaction method as well as a branched DNA probe method. Clinicopathologic
findings were compared between patients with and without viremia and the risk
factors for poor outcome were evaluated. Hepatitis C virus (HCV) RNA was not
detected in the sera from 7 patients (group 1), but was detected in the sera from
the other 52 patients (group 2). Alanine aminotransferase (ALT) activity was
significantly higher in group 2 than in group 1. The proportion of patients with
active hepatitis was significantly higher in group 2. In group 2, new HCC often
developed after the operation and four patients died of liver dysfunction. HCV
viremia, high ALT activity, high concentration of total bilirubin, and liver
cirrhosis were related to recurrence after the operation. Multivariate analysis
indicated that HCV viremia and high ALT activity were independent risk factors
for recurrence of HCC. Continuous hepatitis with persistent HCV viremia worsened
the outcome after the resection of HCC by causing new development of HCC and
deterioration of liver function. In patients with HCV-related HCC, but without
HCV viremia, satisfactory results can be expected after liver resection.
PMID- 10189887
TI - Apoptotic changes precede mitochondrial dysfunction in red cell-type pyruvate
kinase mutant mouse erythroleukemia cell lines.
AB - Two erythroleukemia cell lines have been established from the splenic lesions of
red blood cell-type pyruvate kinase (R-PK) activity-deficient mice of CBA/N
origin infected with a polycythemic strain of Friend leukemia virus complex
(FVp). Ten to 30% of the cells of these cell lines undergo apoptotic changes in
routine passage, as shown by nuclear fragmentation, DNA laddering, DNA content
(propidium iodide (PI) staining), and annexin V binding assay. In these cells,
however, although adenosine 5'-triphosphate (ATP) levels were lower than in the
control cells, the mitochondrial inner transmembrane potential (delta psi m),
detected by rhodamine 123 (R123) and diSC3(5) staining, remained unchanged until
the final stage of apoptosis. No evidence was obtained to relate this finding to
R-PK mutation due to difficulty in cloning stable, conditionally inducible R-PK
gene transfectants. However, low delta psi m in the apoptotic cell population of
the control T3-K-1 (K-1) and T3-CI-2-0 (2-0) Friend erythroleukemia cells
supports a possible relationship, as do results obtained in two Friend
erythroleukemia cells recently isolated from normal CBA/N mice. These cell lines
are expected to be useful for clarifying both the primary apoptotic changes
independent of mitochondrial dysfunction and the PK-isozyme changes during
erythrodifferentiation, for example, the decreased muscle type 2 (M2) PK level.
Modification of growth signals in these cell lines may modulate differentiation
and/or apoptosis and allow further elucidation of the signaling networks.
PMID- 10189888
TI - Activation of caspases in p53-induced transactivation-independent apoptosis.
AB - Though p53-induced apoptosis plays an important role in tumor suppression, the
mechanism(s) by which p53 induces apoptosis is still unclear. To elucidate the
p53-induced apoptotic pathway, we examined the role of p53 transactivation
activity and caspase in J138V5C cells carrying a human temperature-sensitive (ts)
p53 mutant (138Ala-->Val). The results showed that p53-induced apoptosis was not
blocked by cycloheximide, which effectively prevented the expression of p53
target genes, indicating that transactivation was not essential for p53-induced
apoptosis in this system. Western blot analysis showed that PARP, CPP32 and ICH-1
precursors were cleaved during apoptosis. The CPP32-preferential tetrapeptide
inhibitor Ac-DEVD-CHO blocked the cleavage of ICH-1 and PARP precursors,
suggesting that CPP32 or some other DEVD-sensitive caspase(s) is the upstream
activator of ICH-1. We also examined the role of the Fas pathway by using Fas and
Fas ligand-neutralizing antibodies. Both antibodies failed to block p53-induced
apoptosis, suggesting that the Fas pathway was not essential for p53-induced
apoptosis in this system. Taken together, our results indicate that p53-induced,
transactivation-independent apoptosis in Jurkat cells involves sequential
activation of CPP32 or some other DEVD-sensitive caspase(s) and ICH-1, via a Fas
independent pathway.
PMID- 10189889
TI - Detection of apoptotic cells in human colorectal cancer by two different in situ
methods: antibody against single-stranded DNA and terminal deoxynucleotidyl
transferase-mediated dUTP-biotin nick end-labeling (TUNEL) methods.
AB - We comparatively investigated the extent of apoptotic cell loss in human
colorectal cancers evaluated by two methods, namely the conventional terminal
deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)
biotin nick end-labeling (TUNEL) method and immunohistochemistry for single
stranded (ss) DNA. The apoptotic index (AI) obtained with the TUNEL method was
higher than that shown by the immunohistochemistry for ssDNA. However, a
significant correlation in AIs evaluated by these methods was found. The AIs
obtained by both methods were significantly higher in the advanced cancers than
in the early cancers. Cellular proliferation activity was assessed in terms of
positivity rate (PR) for expression of proliferating cell nuclear antigen (PCNA).
The PR of advanced cancers was significantly higher than that of early cancers.
The present results indicate that immunohistochemistry for ssDNA is useful (as is
the TUNEL method) for evaluation of apoptotic tumor cells in colorectal
carcinomas. In addition, it was confirmed that there is a remarkable increase of
not only proliferation activity, but also tumor cell apoptosis in the process of
progression of colon cancer from early to advanced stages of the disease.
PMID- 10189890
TI - Expression of the Wilms' tumor gene WT1 in solid tumors and its involvement in
tumor cell growth.
AB - To determine the role of the Wilms' tumor gene WT1 in tumorigenesis of solid
tumors, expression of the WT1 gene was examined in 34 solid tumor cell lines
(four gastric cancer cell lines, five colon cancer cell lines, 15 lung cancer
cell lines, four breast cancer cell lines, one germ cell tumor cell line, two
ovarian cancer cell lines, one uterine cancer cell line, one thyroid cancer cell
line, and one hepatocellular carcinoma cell line) by means of quantitative
reverse transcriptase-polymerase chain reaction. WT1 gene expression was detected
in three of the four gastric cancer cell lines, all of the five colon cancer cell
lines, 12 of the 15 lung cancer cell lines, two of the four breast cancer cell
lines, the germ cell tumor cell line, the two ovarian cancer cell lines, the
uterine cancer cell line, the thyroid cancer cell line, and the hepatocellular
carcinoma cell line. Therefore, of the 34 solid tumor cell lines examined, 28
(82%) expressed WT1. Three cell lines expressing WT1 (gastric cancer cell line AZ
521, lung cancer cell line OS3, and ovarian cancer cell line TYK-nu) were further
analyzed for mutations and/or deletions in the WT1 gene by means of single-strand
conformation polymorphism analysis. However, no mutations or deletions were
detected in the region of the WT1 gene ranging from the 3' end of exon 1 to exon
10 (the WT1 gene consists of 10 exons) in these three cell lines. Furthermore,
when AZ-521, OS3, and TYK-nu cells were treated with WT1 antisense oligomers, the
growth of these cells was significantly inhibited in association with a reduction
in WT1 protein levels. Furthermore, constitute expression of the transfected WT1
gene in cancer cells inhibited the antisense effect of WT1 antisense oligomer on
cell growth. These results indicated that the WT1 gene plays an essential role in
the growth of solid tumors and performs an oncogenic rather than a tumor
suppressor gene function.
PMID- 10189891
TI - Frequent beta-catenin abnormalities in bone and soft-tissue tumors.
AB - We have screened mutations of the beta-catenin gene by using the polymerase chain
reaction-single strand conformation polymorphism (PCR-SSCP) method in 62
malignant bone and soft-tissue tumors, including malignant fibrous histiocytomas
(MFHs), osteosarcomas, synovial sarcomas, liposarcomas, malignant schwannomas,
and other types of tumors, as well as 11 benign tumors. beta-Catenin-activating
missense mutations were found in two malignant tumors. One found in MFH occurred
at codon 45 and caused an amino acid substitution from serine (one of the GSK3
beta-targeted phosphorylation sites) to phenylalanine. The other, detected in
synovial sarcoma at codon 32, resulted in an amino acid change from aspartic acid
(located adjacent to the phosphorylation target, serine, encoded by codon 33) to
tyrosine. Furthermore, we found accumulation of beta-catenin by western-blotting
analysis in 12 of 19 malignant tumors in which we found no mutation involving
exon 3. Our results suggested the possible involvement of beta-catenin
activation, by beta-catenin gene mutation or alteration of other factor(s), in
the formation and/or progression of various types of bone and soft-tissue tumors.
PMID- 10189892
TI - Overexpression of MDM2 in MCF-7 promotes both growth advantage and p53
accumulation in response to estradiol.
AB - The overexpression of the oncogene product MDM2 is often observed in human breast
cancer cells, especially in estrogen receptor (ER)-positive ones. To study the
role of MDM2 protein in ER-positive breast cancer, we have established cell lines
derived from MCF-7 which stably express increased and decreased levels of MDM2 by
transfection of a mammalian expression vector containing human mdm2 cDNA in sense
and antisense orientations, respectively. Interestingly, MDM2 overexpression in
MCF-7 cells afforded a remarkable growth advantage under estradiol (E2)
supplemented condition. Then, we analyzed the expression of p53, which is an
important regulator of growth and the cell cycle. Unexpectedly, the p53
accumulation induced by E2 was remarkably higher in MCF-7 cells stably
overexpressing MDM2 than in the parent MCF-7 cells. On the other hand, reduction
of MDM2 suppressed the E2-induced increase in p53 protein. Moreover, mdm2
antisense oligonucleotides prevented E2-induced accumulation of p53. In the
steady state, the cellular levels of p53 were also correlated with those of MDM2.
These interactions are not consistent with the well-known role of MDM2, which
acts as a negative regulator for p53 by inhibiting its function and promoting its
rapid degradation. These results suggest that MDM2 may regulate the expression of
p53 in the steady state and in response to E2 in breast cancer cells, and imply a
novel and important role of MDM2 during breast carcinogenesis.
PMID- 10189894
TI - Effective irinotecan (CPT-11)-containing liposomes: intraliposomal conversion to
the active metabolite SN-38.
AB - Irinotecan hydrochloride (CPT-11) is a prodrug of SN-38, which is an active
metabolite with antitumor activity and side toxicity. The activities of CPT-11
and SN-38 depend on the closed lactone ring form of SN-38. We have examined the
tissue distributions of the closed and open forms of CPT-11 and SN-38 in Lewis
lung carcinoma-bearing mice after the administration of liposomal CPT-11 (S-Lip)
and polyethyleneglycol (PEG)-modified S-Lip (S-PEG). The plasma concentrations of
closed CPT-11 and SN-38 were increased by liposomalization, and their blood
circulation was prolonged by the PEG modification. The concentrations of closed
CPT-11 and SN-38 in tumors were elevated by both the liposomalization and PEG
modification. The closed/total ratio of SN-38 in the tumors of the S-PEG group
was greater than that of the CPT-11 solution (Sol) group. Thus, SN-38 was thought
to be generated in intact liposomes containing CPT-11. The bile concentration of
closed SN-38, which is responsible for CPT-11-induced intestinal disorder, was
decreased by liposomalization. In an in vitro experiment, the SN-38/CPT-11 ratio
in the tumor cells of the S-Lip group was found to be higher than that of the Sol
group, and the ratio of the closed form of SN-38 was increased by the
liposomalization. Laser scanning confocal microscopy showed the generation of SN
38 in the liposomal membrane after the incubation of S-Lip with carboxylesterase.
It is therefore considered that a part of CPT-11 is converted to SN-38 in the
intact liposomes.
PMID- 10189893
TI - Differential induction of apoptosis in B16 melanoma and EL-4 lymphoma cells by
cytostatin and bactobolin.
AB - Most solid tumor cells are less sensitive to apoptosis induced by anticancer
drugs than hematopoietic cancer cells. However, the mechanisms of the different
responses to apoptosis in these cell types remain unknown. To explore this
question, we used B16 melanoma and EL-4 lymphoma cells as solid tumor- and
hematopoietic cancer-derived cell lines, and examined the effects of two
apoptosis inducers, cytostatin and bactobolin, on both cell lines. Apoptosis in
B16 cells was induced strongly by bactobolin, but weakly by cytostatin. In
contrast, apoptosis in EL-4 cells was induced strongly by cytostatin, but weakly
by bactobolin. While caspase-3 was activated upon induction of apoptosis in both
cell lines, Ac-DEVD-CHO, a specific inhibitor of caspase-3, suppressed only the
apoptosis in B16 cells. In B16 cells, cyclins E, A, and B1 were decreased by
strongly apoptosis-inducing bactobolin prior to apoptosis commitment, but cyclin
E was not decreased by weakly apoptosis-inducing cytostatin. On the other hand,
in EL-4 cells cyclins D1, E, A, and B1 were decreased by strongly apoptosis
inducing cytostatin prior to apoptosis commitment, but neither cyclin A nor B1
was decreased by weakly apoptosis-inducing bactobolin. These results indicate
that the dependency of apoptosis induction on caspase activity is different
between the two cell lines. Furthermore, there may be an inverse correlation
between specific cyclins and apoptosis induction in the two cell lines.
PMID- 10189895
TI - Prostate-specific membrane antigen-derived primers in a nested reverse
transcription polymerase chain reaction for detecting prostatic cancer cells.
AB - The detection of prostate-specific membrane antigen (PSM) mRNA in the peripheral
blood of prostate cancer patients by a nested reverse transcriptase-polymerase
chain reaction (RT-PCR) assay is a useful and sensitive method for the
identification of small foci of metastatic lesions. In this study, a nested RT
PCR assay was performed using the two different PSM-derived oligonucleotide
primer sets reported by Israeli et al. and Loric et al. (termed PSM primers-1 and
primers-2, respectively, in this report), and the differences in the specificity
and sensitivity of these primer sets for detecting prostate cancer cells in the
blood are discussed. The PCR assay using PSM primers-1 showed DNA bands for 4 of
7 cases of metastatic prostate cancer and amplified the untreated genomic DNA,
while that using PSM primers-2 showed 6 bands without the amplification of the
genomic DNA. In conclusion, PSM primers-2 is superior to PSM primers-1 for the
detection of PSM mRNA in the peripheral blood of prostate cancer patients.
PMID- 10189896
TI - K-ras point mutations in the supernatants of pancreatic juice and bile are
reliable for diagnosis of pancreas and biliary tract carcinomas complementary to
cytologic examination.
AB - In order to clarify whether DNA analysis for K-ras mutation can be used to
diagnose cancers in supernatants of pancreatic juice and bile, samples from 29
cases of pancreatic, biliary tract, gastric, and neuroendocrine carcinomas, 1
malignant lymphoma case, 2 cases of pancreatic adenoma, 9 cases of chronic
pancreatitis and 21 other non-cancer cases were examined. Polymerase chain
reaction (PCR) products for K-ras gene codons 2 to 97 of exons 1 and 2 were
generated with 33/33 (100%) pancreatic juice and 41/41 (100%) bile samples. By
the single strand conformation polymorphism (SSCP) method, point mutations were
detected in the pancreatic juice or bile supernatants of 13/13 (100%) pancreas
cancer cases, 5/14 (35.7%) biliary tract cancer cases, 1/2 (50.0%) pancreatic
adenoma cases and 3/9 (33.3%) chronic pancreatitis cases. Direct sequencing
confirmed identical point mutations in the supernatants, malignant cells of
cytologic smears of pancreatic juice or bile and cancer tissues. The DNA analysis
demonstrated the presence of K-ras point mutations in 3 cases of pancreatic
carcinomas with false-negative cytologic diagnoses. This novel method allows
simultaneous testing for genetic abnormalities in supernatants of pancreatic
juice and bile, after removing cells for cytologic diagnosis and screening for
pancreatic and biliary tract tumors.
PMID- 10189898
TI - [Update on the safety controls for plasma derivatives].
PMID- 10189897
TI - Prognostic factors for short-term survival in patients with stage IV non-small
cell lung cancer.
AB - Prognostic factors which can forecast short-term survival in patients with stage
IV non-small cell lung cancer have not been well evaluated. Characteristics of
such factors may be different from those for overall survival, and would be an
important eligibility criterion for clinical trials of chemotherapy. We
retrospectively analyzed the data of 158 patients with stage IV non-small cell
lung cancer whose performance status was 0, 1 or 2. Univariate and multivariate
logistic regression models revealed demographic variables which significantly
correlated with the survival at 8 or 12 weeks. The univariate model showed the
following significant variables: T factor, N factor, number of organs with
metastases, grade of performance status, weight loss within 6 months, evidence of
metastasis either at bone or lymph node, and lactate dehydrogenase level. The
subsequent multivariate model demonstrated that both grade of performance status
under 2 and number of metastasized organs less than 3 are important factors for 8
or 12-week survival. The survival rate in patients meeting the two criteria
(grade of performance status under 2 and number of metastasized organs less than
3) and in those meeting only one of them was 93% versus 80% at 8 weeks (P =
0.030) and 88% versus 62% at 12 weeks (P < 0.001), respectively. Grade of
performance status and number of organs with metastases appear to be important
prognostic factors for short-term survival in patients with stage IV non-small
cell lung cancer.
PMID- 10189899
TI - [Our experience with the use of ranitidine in the prevention of gastroduodenal
damage caused by antiblastic polychemotherapy].
AB - BACKGROUND AND AIM: Prevention of the adverse effects of antiblastic chemotherapy
on the upper digestive tract through the administration of ranitidine. METHODS: A
heterogeneous group of patients suffering from neoplastic pathologies was
monitored between 1984 and 1998 (204 males and 152 females); patients were aged
between 36 and 80 years old and they were all treated with antineoplastic
polychemotherapy. Preventive therapy with ranitidine at a dose of 300 mg/die per
os in a single evening bolus was continued throughout the entire period of
antiblastic treatment, varying between a minimum of six months and one year or
more. The study was performed at the Outpatient clinic for Surgical Oncology and
Clinical Therapy at the General Surgery Department of Valdichiana Senese, Local
Health Unit 7, Siena. It took the form of a clinical and instrumental follow-up
using esophagogastroduodenoscopy at the time of enrollment and subsequently 3, 6
and 12 months thereafter as required. RESULTS: Ranitidine was found useful as a
means of significantly reducing the gastrolesive effects of antiblastic drugs
which, as has been extensively shown by the literature, can lead to the
suspension of treatment owing to intolerance and even death. In this study
ranitidine reduced the lesive effects on the upper digestive tract in 78% of the
cases studied compared to 22% in non-responders. CONCLUSIONS: The action of
ranitidine made antiblastic treatment more acceptable by mitigating or even
blocking the adverse effects on the stomach and duodenum, thus leading to an
improved quality of life for these cancer patients.
PMID- 10189900
TI - [Muscle fatigue and dyspnea].
AB - Calm breathing requires little effort on the part of the inspiratory muscles to
overcome the elastic and non-elastic resistances of the chest-lung system.
Spontaneous expiration is passive and does not engage the respiratory muscles. In
the event of restriction or obstruction, however, there are changes in these two
types of resistance and their distribution. Extra work is required and the blood
flow through the muscles has a decisive influence on their performance.
Histologically detectable differences in the number of fast or slow, glycolytic
or oxidative fibres in the respiratory muscles correspond to functional
differences. Some muscles are required to supply the force or energy of
contraction, others are concerned with endurance and others with intermediate
situations. The diaphragm is mainly composed of slow-oxidative fibres. It is thus
characterised by its strength, low tension, high repetitive capacity and
incredible endurance. This brief review describes the main concepts of the
physiology of the respiratory muscles. Reference is also made to the mechanisms
of muscle fatigue and dyspnea, two independent or associated clinical situations
that point to the risk of progression to respiratory insufficiency.
PMID- 10189901
TI - [Hepato-splenic and peritoneal tuberculosis. A difficult diagnosis].
AB - Peritoneal tuberculosis is a rare extra-pulmonary location of Mycobacterium
tuberculosis infection arising in the gastrointestinal tract mostly as a
complication of the pulmonary location or seldom as a primary involvement. The
authors report the case of a 18-year old girl admitted in 1996 to the Infectious
Diseases Department of the Umberto I Hospital, "La Sapienza" State University of
Rome for the persistence of fever and dry cough, despite a protracted antibiotic
treatment performed in previous hospital admissions for a suspicious diagnosis of
a "broncho-pneumonia". As the fever didn't decrease and a pain at the right ilium
arose, an anti-tuberculous chemotherapeutic treatment was performed (isoniazid
and rifampicin), that improved the state of the patient. The pain was resolved by
means of a celioscopic operation, showing the evidence of various white nodes on
the peritoneal, hepatic and lienal surfaces; all these pathognomonic signs and
the anti-tuberculous chemotherapy confirmed the diagnosis of "hepatic, lienal and
peritoneal tuberculosis". The patient was subsequently admitted to our institute,
where an anti-tuberculous treatment (isoniazid, rifampicin and pyrazinamide) was
performed, which caused a further resolution of the clinical and radiological
picture.
PMID- 10189902
TI - [A case of idiopathic multiple calcinosis cutis].
AB - A case of calcinosis cutis, appeared since childhood in a woman 73-years-old,
affected by diabetes mellitus with complications, is described. This uncommon
disorder is discussed on the basis of data from recent literature. Calcinosis
cutis is a condition characterized by the deposition of crystals of calcium
phosphate (hydroxyapatite) in the skin. Calcinosis cutis may be idiopathic or
secondary. The idiopathic calcinosis cutis is uncommon, may be solitary or
multiple, sporadic or associated with Down syndrome (MICC or "milialike
idiopathic calcinosis cutis") and appears more often in childhood or adolescence.
Secondary calcinosis cutis may appear in the course of juvenile dermatomyositis
or in the form of systemic scleroderma named CREST syndrome (calcinosis cutis,
Raynaud's phenomenon, esophageal dysfunction, sclerodactyly and telangectasia).
Calcinosis cutis may also be seen later in the course of renal failure,
associated with hyperphosphatemia and secondary hyperparathyroidism. In this case
report, calcinosis cutis appeared early in life and the laboratory data showed
normal erythrocyte sedimentation rate and leukocyte count, negative LE test and
absence of rheumatoid factor and non-organ-specific auto-antibodies, and multiple
localizations. On these grounds, the diagnosis of idiopathic multiple calcinosis
cutis was made. This is a rare and benign syndrome, which does not cause any late
complication and whose prognosis is therefore favourable.
PMID- 10189903
TI - [Strategies for the development of the quality of integrated home care].
AB - Home Health Care (HHC) is a strategy to provide holistic care for elderly,
chronic and terminal patients and for patients early discharged from hospitals.
The aim of this article is to give some advice to ensure social and health
integration, coordination of procedures and family participation in HCC. Moreover
a framework to ensure organization of a HHC service is required and a guideline
to define functions and responsibilities, human and physical resources and
procedures to deliver health care is provided. The first stage of a HHC project
must be an educational programme for the multidisciplinary team involved in home
care. The common education is the strategy to improve Quality of a HHC service,
involving medical and social workers in the definition of their own "criteria and
standards" for organization, resources and procedures.
PMID- 10189904
TI - [Does continuing medical education improve the way physicians conduct their
practice?].
AB - OBJECTIVES: Physicians practicing in France are required to participate in
continuing education programs in accordance with the code of deontology and the
official decree on controlling medical expenditures. We reviewed the literature
to analyze the efficacy of such training on the way physicians conduct their
practice. METHODS: We examined the following educational methodologies: diffusion
of educational documents or guidelines, conferences and presentations,
interventions by opinion leaders, direct visits at the physician's office. The
analysis was based solely on publications issuing from work considered to be
valid in accordance with the Cochrane collaboration: intervention trials,
chronological series, before-after studies with control group. RESULTS: The
diffusion of educational material or more formal continuing education programs do
not appear to have an effect on the way physicians conduct their practice.
Interventions by opinion leaders have a demonstrated impact but are rarely judged
clinically significant. Visits to the physician's office by specially trained
health care workers have an effect but this mode of education is costly.
CONCLUSIONS: The conventional strategies, such as simple information diffusion
and continuing education programs, developed to promote an evolution of clinical
practices appear to be the least effective methodologies.
PMID- 10189907
TI - [Association of Sweet syndrome, sarcoidosis and toxoplasmosis].
PMID- 10189905
TI - [Varicella zoster virus infection area in 39 HIV-infected patients. Therapeutic
management].
AB - OBJECTIVES: The main goal of this study was to assess therapeutic strategies in
HIV-infected patients with varicella-zoster virus infection. PATIENTS AND
METHODS: This retrospective study conducted between 1989 and 1996 concerned 39
HIV-infected patients who had reached the AIDS stage and had at least one episode
of varcella-zoster infection. Epidemiological, clinical and therapeutic data were
recorded. Chi-squared test was used for comparisons. RESULTS: A total of 78
episodes of varicella-zoster infection occurred including 39 primary episodes and
39 recurrences. Aciclovir (ACV) 200 mg per os was given in 27 cases as first
intention therapy (mean dose 4000 mg/day for a mean 10 days), ACV 800 mg per os
in 10 cases (mean dose 4000 mg per day for a mean 10 days), and intravenous ACV
in 23 cases (mean dose 30 mg/kg/day for a mean 7 days). Foscarnet was used 5
times, 90-100 mg per day for 8 to 21 days. We did not observe any difference in
efficacy between the three ACV formulations, probably because of the small number
of patients in the series and the retrospective nature of the study. All of the
failures of the oral treatments occurred in patients with CD4 counts below
100/mm3. CONCLUSION: Aciclovir (800 mg) can be given in HIV-infected patients who
develop non-complicated varicella-zoster virus infection. Intravenous aciclovir
should be reserved for severe disseminated and/or neurological forms and for
highly immunodepressed patients (for example those with a CD4 count below
200/mm3). These findings should be confirmed by prospective studies.
PMID- 10189906
TI - [Distal Miyoshi muscular dystrophy in a Moroccan patient].
AB - BACKGROUND: Muscular dystrophy usually involves a deficiency in the proximal
muscles. We report a case of distal muscular dystrophy in a Moroccan patient.
CASE REPORT: A 21-year-old Moroccan complained of progressive onset weakness of
the lower limbs and frequent falls. The neurological examination demonstrated
amyotrophy involving both legs and almost complete regression of the posterior
muscle compartment. Clinical findings were confirmed by muscle scans. The
electromyogram showed a progressive myogenic process. Creatine kinase was
elevated. The severe dystrophic aspect was evidenced at muscle biopsy and led to
the diagnosis of distal Miyoshi muscular dystrophy. DISCUSSION: Miyoshi muscular
dystrophy, a distal myopathy transmitted by autosomal recessive inheritance, is
usually observed in young adults who present characteristic amyotrophy of the
posterior leg muscles. The proximal muscles of the lower and upper limbs may
become involved during the disease course. Approximately one-third of the
patients require wheel chair assistance after 10 years. Creatine kinase levels
are constantly elevated. The differential diagnosis with other muscular
dystrophies predominating in the distal muscles, particularly Steinert's myotonic
dystrophy and inclusion body myositis, is discussed.
PMID- 10189908
TI - [Ptosis revealing primary infection by Parvovirus B19].
PMID- 10189909
TI - [Primary cytomegalovirus infection with anti-ribosomal P protein antibodies].
PMID- 10189910
TI - [Acupuncture: a certain degree of recognition].
PMID- 10189911
TI - [Management of postoperative pain in adults and children].
PMID- 10189912
TI - [Development of pharmaco-epidemiology in France].
AB - A new scientific discipline: Progress in scientific knowledge, advances in
therapeutic innovation, the development of new drugs and the continuing need for
optimal drug use impose a new approach to the rational assessment of public
health needs and the risks and benefits of therapeutic intervention. In the near
future, a new scientific discipline, pharmaceutical epidemiology, will play a
leading role. France seems to be a bit behind other western countries in this
area. Goal setting: The objectives of industrial firms do not necessarily cover
all aspects of the overall goals of society. If the scientific community leaves
the development and implementation of pharmaceutical epidemiology in the hands of
industrial firms alone, they risk seeing its field of action limited to
industrial objectives. The goals of this new discipline must be defined within an
unbiased framework aimed at meeting the needs of society in general.
Organization: The development of pharmaceutical epidemiology as an integral part
of medical research requires a clear definition of its objectives, methods,
working hypotheses and time and human allocations. In this context,
pharmaceutical epidemiology should be organized within the University and
scientific settings currently contributing to scientific research in France
(INSERM, CNRS, ORSTOM, etc.). Creating favorable conditions: A pharmaceutical
epidemiology network with adequate human and material resources is needed. The
wide range of needs expressed by existing institutions (Drug Agency, Prescription
and Drug Use Observatory, industrial firms, the national health insurance system,
physician and pharmacist associations) pleads for a nationally organized project
working in the public domain.
PMID- 10189913
TI - [New requirements in the primary treatment of arterial hypertension: why do we
need fixed low-dose combination therapy?].
AB - The latest results of studies and therapeutic trials have shown the following:
Present therapeutic strategies for arterial hypertension have a certain efficacy,
but appear to have reached a plateau. Arterial hypertension essentially affects
older subjects who can benefit from the advantages of antihypertensive treatment
as much as, if not more than, younger subjects. A better evaluation of the
cardiovascular risk of the patient is essential: This should include all the
components of arterial hypertension (diastolic and systolic blood pressures and
pulse pressure), risk factors, associated pathologies, and target-organ damage.
Such an evaluation will help fix therapeutic objectives tailored to individual
patientsi needs. The limitations of monotherapy in achieving this objective: They
are demonstrated in clinical practise, as well as in large-scale trials. In this
context, new strategies based on the first-line use of fixed very-low-dose
combination therapies appear to be both useful and promising, as well as being in
line with the latest recommendations.
PMID- 10189914
TI - [Images in medicine. Venous aneurysm].
PMID- 10189915
TI - [The conclusion of the XXXVIII the SIRM National Congress. Milano, 23-27 May,
1998].
PMID- 10189916
TI - [Role of high-definition and high frequency ultrasonography in determining tumor
thickness in cutaneous malignant melanoma].
AB - PURPOSE: We investigated the predictive capabilities of high frequency, high
resolution ultrasound (US) in the preoperative assessment of tumor thickness in
cutaneous malignant melanomas. This evaluation is a valuable help for correct
surgical planning. MATERIAL AND METHODS: December 1997 to August 1998, we studied
with US over 120 pigmented skin lesions and collected the data, including the
final histologic diagnosis, of 78 of them, which make our series. Sixty-six of 78
lesions were histologically defined as cutaneous malignant melanomas with
superficial spread and the other 12 as melanocytic nevi. All examinations were
carried out with an Esaotebiomedica AU 5 Harmonic scanner equipped with a 20-MHz
annular array probe and a linear 13-MHz probe; B-mode, color and power Doppler
images were always acquired. RESULTS: The statistical analysis of the comparative
US and histologic measurements of tumor thickness showed very good agreement,
with a high Pearson's coefficient (R: .93). However, US frequently underestimated
the actual thickness relative to histology, which is in contradiction with
previous literature reports. We could study with US the melanoma in situ, which
has never been described before. Last but not least, low-thickness melanomas had
very few color and power Doppler signals. CONCLUSIONS: US is the correct tool for
the preoperative assessment of the thickness of cutaneous malignant melanomas
because it provides high agreement with histologic data even in lesions thinner
than 1 mm.
PMID- 10189917
TI - [Extracerebral neoplastic manifestations in neurofibromatosis 1: integrated
diagnostic imaging].
AB - PURPOSE: To analyze the extracerebral manifestations of type 1 neurofibromatosis
(NF-1), with special reference to peripheral nerve tumors. MATERIAL AND METHODS:
The findings of 376 NF-1 patients (194 men and 182 women; age range: 0.1-48
years, mean: 8.1) were retrospectively reviewed. The patients had been submitted
to abdominopelvic and superficial US and, in case of abnormal US findings or in
the presence of symptoms, to CT and/or MRI. In addition, we considered 5 more
patients (2 men and 3 women; age range: 50-72 years, mean: 64.4) with incomplete
forms of NF-1 diagnosed after the finding of nerve sheath tumors. Biopsy (12
cases), surgery (10 cases), or clinical-instrumental follow-up were the study
criteria. RESULTS: In the first group of patients we identified 91 cutaneous, 222
subcutaneous, 11 pendulous and 25 internal neurofibromas. Plexiform neurofibromas
were found in the neck (1 case), chest (6 cases), abdomen (16), pelvis (8). We
also found 1 benign and 1 malignant Schwannomas, 2 nerve sheath fibrosarcomas, 1
dopamine-producing sympatoma and 1 spermacytoma. As for the second group of
patients, we had 2 Schwannomas, 1 pulmonary neurofibroma, and 2 multiple
plexiform neurofibromas. The neurofibromas exhibited homogeneous US
hypoechogenicity or slight echogenicity, with little contrast enhancement at CT.
MR showed peripheral hyperintensity and central hypointensity on T2-weighted
sequences and marked contrast enhancement after gadolinium, sometimes with mostly
central uptake. The plexiform neurofibromas, which are typical of NF-1, had
poorly-defined or infiltrating margins, with similar findings to the previous
ones but sometimes with less homogeneous patterns at both US and CT. The
Schwannomas, which are a less common finding in NF-1, exhibited different
features at MRI and CT, namely pseudo-liquid or solid-inhomogeneous patterns with
irregular and inhomogeneous contrast enhancement relative to the Antoni A/B tumor
component. In the malignant lesions we observed infiltrating patterns, with
irregular and inhomogeneous contrast enhancement, arranged asymmetrically
relative to the contralateral lesion. CONCLUSIONS: Extra-axial neoplasms are a
frequent finding in NF-1. Despite the extremely variable appearances of some
lesions (particularly Schwannomas), the typical plexiform neurofibroma exhibits
characteristic patterns. The diagnosis of malignancy often requires bioptic
confirmation.
PMID- 10189918
TI - [Digital rotational angiography in the study of vascular diseases: technical note
and initial clinical applications].
AB - INTRODUCTION: Digital rotational angiography is a technique characterized by a C
arm acquiring images as it rapidly rotates around the patient. We studied the
clinical potentials of this technique in the assessment of vascular diseases of
the abdominal aorta and of the carotid, lower limbs and renal arteries. MATERIAL
AND METHODS: We examined 108 patients (66 men and 42 women; mean age: 54.3 years,
range: 34-69): 42 had vascular diseases in the carotid arteries, 47 in the
abdominal aorta and lower limbs and 19 in the renal arteries. All the patients
underwent digital rotational and non-rotational angiography and we analyzed the
diagnostic yield, amount of contrast agent and the utility of additional views
for each technique. All the examinations were reviewed with(out) subtraction, in
cine-loop mode and frame by frame, as well as with(out) magnification. Finally,
we considered background noise in both rotational and non-rotational images.
RESULTS: The diagnostic quality of the digital rotational technique was always
the same as or superior to that of the non-rotational technique. The former
allows better 3D rendering, especially when viewed in the cine-loop mode; the
examination is shorter and less contrast agent is needed. In contrast, image
noise was increased, especially in lateral and oblique views. Digital rotational
angiography was fairly well tolerated but the long breath-hold required was a
problem especially to elderly patients. CONCLUSIONS: Digital rotational
angiography is a useful tool to study vascular diseases in the carotid arteries
and lower limbs using a lower radiation dose and less contrast agent than non
rotational examinations. As for the abdominal aorta and renal arteries, the
rotational technique can be a valid adjunct to the conventional one.
PMID- 10189919
TI - [Integrated study of fecal incontinence with defecography, anal ultrasonography,
perineography, and manometry].
AB - INTRODUCTION: Imaging methods such as defecography, anal US and perineography,
combined with manometry, now permit to identify a growing number of causes of
anorectal and pelvic floor deficiency. Fecal incontinence patients can thus be
approached correctly relative to both diagnosis and treatment. We investigated
the role of these techniques in the work-up of fecal incontinence. MATERIAL AND
METHODS: Thirty-eight subjects suffering from fecal incontinence were examined.
Defecography was carried out with a special commode and videorecorded on a VHS
cassette. Anal US was performed with a 7-MHz rotating probe (type 1846) with 3-cm
focus length. Perineography was carried out in 15 female patients. RESULTS: The
anorectal angle (ARA) at rest was increased (mean: 106 degrees; normal range: 90
100 degrees) in 34 cases; involuntary barium leakage was seen in 8 patients,
especially on coughing. On squeezing, ARA was normal in 10 cases (mean: 72
degrees; normal range: 60-90 degrees); in 5 cases of puborectal hypotonia there
was no angular excursion between rest and squeezing (mean: 105 degrees). During
evacuation, the average ARA value was 166 degrees in 21 cases and ARA stretched
to verticalization in 8 cases (mean: 179 degrees). Morphofunctional anorectal
changes appeared as rectal mucosal prolapse (12 cases), rectocele (10 cases),
perineal descent syndrome (8 cases) and external rectal prolapse (3 cases). Anal
US identified 15 interruptions in sphincterial rings: 12 patterns were
hypoechoic, 2 mixed and 1 hyperechoic. Atrophic thinning of internal anal
sphincter was seen in 5 idiopathic incontinence patients. Perineography
demonstrated cystocele in 5 cases and cystourethrocele in 1 case. Manometry
showed sphincterial hypotonia at rest in 15 cases, lower values of anorectal
pressure on squeezing in 8 and smaller air volumes inhibiting external
sphincterial tone in 19 cases. CONCLUSIONS: Defecographic studies with evaluation
of ARA and its changes are an important tool with high diagnostic yield. When
combined with other techniques, they provide differential criteria for
sphincterial and puborectal causes and permits to identify associated pelvic
floor dysfunctions. We believe that defecography, anal US (and perineography in
complex disorders) are necessary techniques for the correct clinical approach to
fecal incontinence patients, whose role and diagnostic yield are a valid support
to manometry.
PMID- 10189921
TI - [Post-cholecystectomy syndrome: hepatobiliary scintigraphy and
cholangiopancreatography with magnetic resonance in 5 consecutive patients.
Comparison of results and integrated diagnosis].
AB - PURPOSE: To investigate the clinical effectiveness of combined hepatobiliary
scintigraphy (HBS) and MR-cholangiopancreatography (MRCP) studies in the
postcholecystectomy syndrome. MATERIAL AND METHODS: June 1997, to February 1998,
we examined with HBS and MRCP five women, three of them submitted to surgical and
two to laparoscopic cholecystectomy. All patients had biliary pain but no changes
in cholestasis and liver function blood parameters. After at least 4 hours'
fasting HBS was performed dynamically, for one hour, injecting a 185 MBq 99mTc
mebrofenin bolus i.v. A fatty meal was given at the end of the basal test and
serial static images were acquired till complete biliary washout. RESULTS: MRCP
was normal in one case while in the others it showed biliary tree dilation,
severe stricture of the distal common bile duct (CBD) and marked enlargement of
the remnant cystic duct (RCD), which lodged a 6-mm stone in one patient.
Pancreatic ducts were regular. HBS showed delayed biliary transit in all
patients, which was however completed within 3 hours of injection, favored by the
fatty meal. The RCD was not injected in three cases. Finally, HBS detected an
early liver dysfunction in three cases. DISCUSSION: HBS and MRCP allow to
evaluate the biliary tree function and anatomy, respectively, adding further data
on liver function and pancreatic duct morphology. We detected associated
functional and organic biliary alterations which were the likely cause of
postcholecystectomy pain, such as severe spasm in Oddi's sphincter, nonpatent
enlarged RCD and RCD stones. Moreover, HBS detected an early liver dysfunction in
three cases. In conclusion, combined HBS and MRCP studies make a noninvasive,
simple and accurate diagnostic approach in postcholecystectomy syndrome and for
the screening of patients needing prompt surgical treatment.
PMID- 10189920
TI - [Hepatic focal lesions: role of color Doppler ultrasonography with contrast
media].
AB - INTRODUCTION: The differential diagnosis of focal hepatic lesions is still
studied by diagnostic imaging operators. A big step forward in the field of
ultrasound (US) has come from the color Doppler mode permitting accurate studies
of the vascularization of focal hepatic lesions. Echocontrast agents have further
improved color Doppler sensitivity to slow flows and have permitted to visualize
intralesional vascular signals which were missed at B-mode US. New data have thus
been acquired which can be integrated with flowmetric findings to help make the
correct differential diagnosis with a fair safety margin. We studied the
pathognomonic US pattern for each type of lesion. MATERIAL AND METHODS: We
examined 55 patients with single hepatic lesions which had already been typified:
they were 10 hepatic angiomas, 3 focal nodular hyperplasias (FNH), 2 hepatic
adenomas, 20 hepatocarcinomas and 20 hepatic metastases. Color Doppler
investigations were performed on each patient before and after the intravenous
(i.v.) administration of an echocontrast agent (Levovist, Schering AG, Berlin,
Germany). For each lesion we studied the morphological characteristics, the
resistance index (RI) of intralesional arterial vessels, the hepatic perfusion
index and the maximum speed in intralesional vessels. RESULTS: Contrast-enhanced
US showed no intralesional signals or afferent branches in 8 hepatic angiomas,
which however exhibited some peripheral vascularization; weak intralesional
vascular signals were demonstrated in 2 cavernous angiomas. Intralesional
signals, as well as peripheral vascularization, were detected in the 3 FNH cases,
which also exhibited a centripetal afferent branch; the hepatic perfusion index
in these lesions never exceeded .25. The two hepatic adenomas had similar color
flowmetry to FNH also after i.v. contrast agent administration, except for the
contripetal afferent vessel which was not seen. In the 20 hepatocarcinomas,
contrast-enhanced images showed numerous intralesional signals and afferent
branches which, with the peripheral vascularization, resulted in a basket-like
pattern. Flowmetry of intralesional arterial vessels showed an irregular
systodiastolic range, with RI = .32 +/- .5 in 12 lesions and high in the
remaining 8 lesions (RI = .82 +/- 10). The hepatic perfusion index was .65 +/- 10
in all patients. In 14 of the 20 hepatic metastases, B-mode US showed no
intralesional signals except for 6 metastases from colorectal carcinoma, and
contrast-enhanced findings were about the same. The hepatic perfusion index at
flowmetry ranged .30 to .45 in all patients.
PMID- 10189922
TI - [Gallbladder blunt trauma: comparison between radiologic and anatomo-surgical
findings].
AB - PURPOSE: To assess the diagnostic accuracy and the possible role of
ultrasonography (US) and Computed Tomography (CT) in a small group of patients
who had a blunt abdominal trauma involving the gallbladder. MATERIAL AND METHODS:
We retrospectively reviewed the US and CT findings of five patients with
surgically confirmed post-traumatic gallbladder injury. The whole series
consisted of 196 consecutive patients submitted to laparotomy for blunt abdominal
trauma in the past 7 years. The following US and CT findings were considered at
least suggestive of a possible post-traumatic gallbladder injury: pericholecystic
fluid collection, ill-defined wall margin, collapsed lumen, high intraluminal
density. RESULTS: At surgery, the following findings were observed: gallbladder
hematoma (1 case), acute colecystitis (1 cases), gallbladder tear (3 cases),
gallbladder tear associated with post-traumatic hepatic injuries (2 cases),
duodenal tear (2 cases), hemoperitoneum alone (2 cases), hemoperitoneum
associated with choleperitoneum (1 case), choleperitoneum alone (1 case). The US
and CT findings were pericholecystic fluid collections (4 cases), ill-defined
gallbladder wall margins (3 cases), collapsed lumen with intraluminal high
density (1 case) and free intraperitoneal fluid collections (4 cases). They were
suggestive of a possible post-traumatic gallbladder injury in all the five
patients. CONCLUSIONS: The radiologic findings of our five patients were
suggestive of a gallbladder damage but did not permit to distinguish minor from
major injuries, the latter requiring surgical treatment. US proves to be a useful
screening tool which can also help timing surgery in these patients. CT confirmed
the US suspicions and also permitted accurate assessment of associated post
traumatic injuries to the liver and duodenum. Nevertheless, the clinical
presentation was the most important factor as to the therapeutic management of
these blunt abdominal trauma patients.
PMID- 10189923
TI - [Lymphadenopathy as specific ultrasonography index of subacute thyroiditis.
Preliminary data].
AB - INTRODUCTION: We report the preliminary results of a study on the importance of
juxtajugular and supraisthmian lymph node enlargement at US as a sign of occult
subacute thyroiditis. MATERIAL AND METHODS: We examined patients submitted to
thyroid US for noninflammatory thyroid conditions and for positive familiarity
and studied the presence of supraisthmian and juxtajugular lymph node
enlargement. The patients were then divided into two groups: the clinical
history, antibody titer and symptoms were studied in group A (patients with
enlarged lymph nodes) and the antibody titer, symptoms and US findings were
studied in group B (patients with a history of thyroiditis). RESULTS: Fifty-nine
of 600 patients were allocated to group A and 25 of 600 to group B. Of the former
59 asymptomatic patients (10% of the total), 29% had supraisthmian and 85%
juxtajugular lymph node enlargement, with some patients positive at both sites.
Forty-seven patients (80%) had subacute thyroiditis (33 of them with positive
antibodies and 23 with a clinical history); we had 12 false positives. Twenty-two
of 25 group B patients (91%) had supraisthmian (40%) or juxtajugular (83%) lymph
node enlargement: 3 patients with no enlarged lymph nodes had an over 3-year
history of low antibody titers. DISCUSSION: Forty-seven of 600 (8%) asymptomatic
patients who had been never examined are or were affected with subacute
thyroiditis. Ninety-one per cent of all thyroiditis patients had supraisthmian or
juxtajugular lymph node enlargement, more frequently the latter than the former.
CONCLUSIONS: Supraisthmian and/or juxtajugular lymph node enlargement appears to
be a very useful US sign of subacute thyroiditis, even though these data need
confirmation from larger series of patients.
PMID- 10189924
TI - [Description of an original method of interventional treatment of sialolithiasis
to complement surgery, and report of a case].
PMID- 10189925
TI - [Computerized tomography in the study of jejuno-ileal perforations. Personal case
load].
AB - INTRODUCTION: The most frequent cause of pneumoperitoneum is gastroduodenal
ulcer. Perforations of the small bowel are uncommon compared with perforations of
the rest of the alimentary tract and radiological findings of jejunoileal
perforation have not been frequently reported. The aim of our retrospective study
was to assess the CT findings in 18 patients with jejunoileal perforation.
MATERIAL AND METHODS: We retrospectively reviewed the CT findings in 18 patients
(12 men and 6 women, age ranging 14 to 84 years, mean age 42 years) operated for
jejunoileal perforation at Cardarelli Hospital, Naples. CT examination was
performed in all patients after i.v. injection of contrast medium and in two
cases after oral contrast medium administration. Free intraperitoneal air,
extravasation of ingested contrast media and visualization of a discontinuity in
the bowel wall were considered direct findings of jejunoileal perforation, while
intraperitoneal free fluid, thickened bowel wall and the presence of a streaky
density within the mesentery were considered indirect diagnostic findings.
RESULTS: The site of perforation was the jejunum in 6 cases and the ileum in 12
cases. The following CT findings were retrospectively observed: intraperitoneal
free fluid (61%), free intraperitoneal air (33%), thickened bowel wall (22.2%),
presence of a streaky density within the mesentery (5.5%). Visualization of a
discontinuity in the bowel wall and extravasation of ingested contrast media were
never seen. We observed two findings of perforation in 7 cases, and a single
finding in 8 cases. CT examination was negative in 3 cases. CONCLUSIONS:
Jejunoileal perforations are difficult to identify by CT. In our series, free
intraperitoneal air, as a direct finding of perforation, was observed in 33% of
cases, while free intraperitoneal fluid, as an indirect diagnostic finding, was
the most frequent sign.
PMID- 10189926
TI - [Radiation protection in the use of tracers in radioguided breast surgery].
AB - PURPOSE: Recent techniques in nuclear medicine have permitted to implement new
procedures useful in surgery. Among these, the procedures for locating sentinel
lymph nodes and nonpalpable breast lesions are of great interest. The protocols
for the location of the sentinel lymph node and for the radioguided location of
occult lesions developed at the European Institute of Oncology (IEO, Milan) are
based on the administration of radiopharmaceuticals labelled with Technetium-99m
(99mTc). We evaluated the dosimetric data relative to patients and hospital
personnel to assess whether specific radiation protection procedures are needed.
MATERIAL AND METHODS: Fifty patients with nonpalpable breast lesions and 50
patients with suspected lymph node involvement were enrolled in this study. All
the patients underwent surgery the day after in-loco administration of the
radiopharmaceutical (11 MBq of 99mTc). The absorbed dose to the hospital
personnel was estimated from the air kerma rate measured by ionization chamber at
different distances from the patients at 0 and 16 hours after the
radiopharmaceutical administration. In order to evaluate radiation protection for
patients, absorbed doses were measured positioning thermoluminescent dosimeters
on the patient's skin for about 16 hours. In the operating room, activity was
measured on some excised tissues (lymph nodes and tumors) and on surgical
instruments. RESULTS: Absorbed doses were very low for the clinical staff also in
case of prolonged patient assistance. After 100 cases, the surgeon mean absorbed
dose to the hands and mean effective dose were .45 mGy and .09 mGy, respectively.
These values correspond to 1% of the annual dose limit to the hands and to 10% of
the annual equivalent effective dose recommended for the population (ICRP 60 and
law by decree 230/95). The absorbed dose to healthy tissues of the patients were
lower than 1 mGy (mean values: contralateral breast: .9 mGy; abdomen .45 mGy).
The mean activity detected in the excised tissues was 9 kBq and 900 kBq in the
sentinel lymph nodes and in the tumor lesions (injection site), respectively. The
activity detected on the surgical instruments, higher on gauzes (< 100 kBq), was
negligible. CONCLUSIONS: From the radiation protection point of view, the data
support the validity of our protocols. Absorbed doses to the hospital personnel
are low and require neither a radiation protection control nor a classification
of exposed workers as classes A or B. Special containers for radioactive wastes
are necessary in the administration room but not in the operating room, where the
levels of possible contamination are negligible.
PMID- 10189927
TI - [External exposure of hot cell operators in nuclear medicine].
AB - PURPOSE: The coming into effect of decrees No. 626/94, 242/96 and 230/95 has once
again brought out the problem of the radiation exposure of hot cell operators in
nuclear medicine. MATERIAL AND METHODS: With regard to the activity of the
Division of Nuclear Medicine of the Istituto Nazionale Tumori in Milan, a map has
been produced of the radiation fields in the hot cell in- and outside the working
station by measuring the rate of exposure and evaluating the radiation energy
using film dosimeters in multifilter containers. The individual doses were
measured with film dosimeters for the sternum, the back of the hand and the
wrist, and with thermoluminescent dosimeters for the fingers and forehead. The
thermoluminescent ring was worn with the detector towards the palm and towards
the back of the hand in order to identify the side that was exposed most; the
film dosimeter on the sternum was worn both underneath and above the lead apron
to reveal a possible reduction in overall exposure due to attenuation of the
lower-energy components. RESULTS: The diffuse radiation field in the hot cell
during the usual working activity amounts to 1 microSv/h. Assessment of the
energy of the radiation fields within the working station revealed a higher
energy (90 to 140 keV) in the source storage area than in the area where the
syringes are prepared, the latter being affected by diffuse radiation with
components of approximately 35, 90 and 110 keV. The hand of the operator is
unevenly exposed to the diffuse radiation field and the fingers are more exposed
than the back of the hand and the wrist: when the thermoluminescent ring was worn
with the detector towards the palm of the hand the measured values did not show a
higher exposure than when it was worn with the detector towards the back of the
hand. The equivalent of the overall dose measured underneath the lead apron did
not show any relevant reduction of the exposure due to attenuation of the lower
energy component (approx. 35 keV). We report the dosimetric findings regarding
the total and partial exposure of four different operators during their regular
weekly shift, with the dosimeters for the sternum, ring finger and forehead being
replaced daily. The average equivalent of the dose to the hand for the
manipulation of 37 GBq of 99mTc, measured with a thermoluminescent ring on the
proximal phalanx of the ring finger, ranged 3.9 mSv to 2.0 mSv. Except in one
case, the sternum and forehead proved to be well protected by the shielding of
the working station. DISCUSSION: The operator who stay in the hot cell for 5
hours/week accumulates, due to the presence of diffuse radiation, 5 microSv/week
to the whole body; when his/her hands are inside the working station for 2.5
hours/week in the most unfavorable conditions as regards the presence of
radioactive sources, they will be exposed to 1250 microSv/week, independently of
dose preparation. The exposure of hot cell personnel is highly dependent on the
ergonomics of the operator (build, height, arm spread, hand size, etc.) with
respect to the position of the apertures and the inspection windows of the
working station; as a consequence, the three dosimetric values (exposure of the
sternum, the hands and the forehead) cannot be correlated. The fingers are the
most exposed part of the hand, which confirms the appropriateness of our choice
of the thermoluminescent ring to measure the partial exposure of the hands. Our
results have been compared with those reported in the literature and with
statistical data relative to three years of regular activity (1994-1996), during
which the hot cell operators were monitored according to the same parameters;
female operators proved to be more exposed than males, with average yearly
equivalents of the total dose of 2764 microSv and 860 microSv, respectively, and
average yearly equivalents of the partial dose to the hands of 32,288 microSv and
9460 microSv, respectively. The average total partial dose equivalent rati
PMID- 10189928
TI - [Hemangiomyolipoma of the vastus lateralis. A case report].
PMID- 10189929
TI - [Hyperbaric oxygen therapy in a patient with bilateral Legg-Calve-Perthes
disease].
PMID- 10189930
TI - [Spontaneous rupture of intracranial dermoid cyst. Report of a case].
PMID- 10189931
TI - [Curvilinear lipoma of the corpus callosum associated with lipoma of the choroid
plexus. Report of a case].
PMID- 10189932
TI - [Unusual case of bilateral blow-out fracture of the orbital floor].
PMID- 10189933
TI - [Cervical aortic arch and pseudocoarctation. Report of a case].
PMID- 10189934
TI - [Pseudoaneurysm of the midcolic artery secondary to pancreatitis. Computerized
tomography features after transcatheter embolization].
PMID- 10189935
TI - [Diffuse intestinal lipomatosis associated with pancreatic and adrenal lipomas.
Diagnosis with computerized tomography: the first case?].
PMID- 10189936
TI - [Hepatic artery sectorial enhancement as a sign of acute portal thrombosis.
Report of 3 cases].
PMID- 10189937
TI - [A case of lithiasic gastric obstruction caused by cholecysto-gastric fistula].
PMID- 10189938
TI - [Atypical Bouveret syndrome: gallbladder calculus migrated to the stomach in
biliary ileus. Report of a case].
PMID- 10189939
TI - [Giant adrenal cyst. Report of a case treated with percutaneous aspiration].
PMID- 10189940
TI - [Unusual migratory pneumonitis].
PMID- 10189941
TI - [Vertebral osteolysis: but what kind?].
PMID- 10189942
TI - New drugs from nature--it could be yew.
PMID- 10189943
TI - Effects of the aqueous fraction of the ethanol extract of the leaves of
Cissampelos sympodialis Eichl. in human neutrophils.
AB - An aqueous fraction (10-300 micrograms/mL) of the ethanol extract of the leaves
of Cissampelos sympodialis Eichl inhibited N-formyl-Met-Leu-Phe (fMLP)-induced
release of lysozyme and myeloperoxidase from human neutrophils. Inhibition by the
fraction, as well as by dibutyryl-cAMP and prostaglandin E2, was substantially
greater when the cells were pretreated with the phosphodiesterase (PDE) inhibitor
isobutyl methyl xanthine (IBMX) indicating that the effect may be mediated by
cAMP. Measurement of intracellular cAMP levels showed that the fraction (30-100
micrograms/mL) increased the nucleotide levels in IBMX-pretreated neutrophils
which was unaffected by propranolol. Cyclic AMP dependent protein kinase A
activity was also increased by the fraction (1.5-100 micrograms/mL). Superoxide
anion generation induced by fMLP in cytochalasin B-treated cells primed with PAF
was not inhibited by the aqueous fraction. The results indicate that the aqueous
fraction of Cissampelos sympodialis inhibits neutrophil degranulation by a cAMP
dependent mechanism which may be relevant to the use of the plant as an anti
asthmatic agent in folk medicine.
PMID- 10189944
TI - A Japanese herbal medicine, Chujo-to, has a beneficial effect on osteoporosis in
rats.
AB - The inhibitory effects of a Japanese herbal medicine, Chujo-to, on the progress
of bone loss induced by ovariectomy in rats were investigated. Ovariectomized
rats were administered with Chujo-to during weeks 7-14 after ovariectomy. At 14
weeks, the bone mineral density of the tibia from ovariectomized (OVX) rats had
decreased by 27% compared with those in the sham-operated rats, and by a 18%-21%
and 16% decrease after the administration of Chujo-to and 17 beta-oestradiol,
respectively. The surface of a trabecular bone of the tibia in ovariectomized
rats had a porous and fibrous appearance, while that of the same bone in sham
operated rats was composed of fine particles. After the administration of Chujo
to or 17 beta-oestradiol, the surface of trabecular bone maintained the porous
and fibrous appearance. The uterine weight was not restored by Chujo-to but by 17
beta-oestradiol. These results suggest that Chujo-to has an efficacy on the
osteoporosis of rats similar to 17 beta-oestradiol, but with a different
mechanism.
PMID- 10189945
TI - Analgesic activity of Nepeta italica L.
AB - A screening study was performed on/by essential oils of Nepeta viscida Boiss and
Nepeta italica L. using tail-flick and tail immersion (52.5 degrees C) methods.
N. italica samples were collected from three different localities of Turkey.
Surprisingly, only one of the essential oils showed significant activity, which
was blocked by naloxone, indicating the involvement of opioid receptors. This was
seen only with the mechanical but not the thermal algesic stimulus, suggesting a
specific activity on opioid receptors, excluding mu receptors. The same, active
essential oil also exhibited a non-competitive inhibition of acetylcholine
contractions of isolated rat ileum but it was inactive on the isolated rat aorta.
Furthermore, a correlation between the analgesic activity and the amount of 1,8
cineole was noticed.
PMID- 10189946
TI - Antihepatotoxic activity of Swertia chirata on carbon tetrachloride induced
hepatotoxicity in rats.
AB - The methanol extract of Swertia chirata was evaluated for antihepatotoxic
activity against carbon tetrachloride induced liver toxicity in experimental
rats. The extract was found to be active and on fractionation into butanol
soluble and chloroform soluble fractions, the activity was traced and found more
profound in the chloroform soluble fraction. The butanol soluble bitter rich
fraction showed marginal activity. The results based on biochemical estimations
have been expressed statistically and are additionally supported by
histopathological examination of the liver of experimental rats and
pentobarbitone induced sleep time studies in mice.
PMID- 10189947
TI - Inhibitory effects of Sudanese plant extracts on HIV-1 replication and HIV-1
protease.
AB - Forty-eight methanol and aqueous extracts from Sudanese plants were screened for
their inhibitory activity on viral replication. Nineteen extracts showed
inhibitory effects on HIV-induced cytopathic effects (CPE) on MT-4 cells. The
extracts were further screened against HIV-1 protease (PR) using an HPLC assay
method. Of the tested extracts, the methanol extracts of Acacia nilotica (bark
and pods), Euphorbia granulata (leaves), Maytenus senegalensis (stem-bark) and
aqueous extracts of A. nilotica (pods) and M. senegalensis (stem-bark) showed
considerable inhibitory effects against HIV-1 PR. Inhibitory principles were
isolated from M. senegalensis and their activities were also discussed.
PMID- 10189948
TI - Inhibitory effects of Indonesian medicinal plants on the infection of herpes
simplex virus type 1.
AB - Water and methanol extracts of 30 traditional medicinal plants, collected in
Indonesia, were tested for their anti HSV-1 activity. The extracts of eight plant
species showed potent activity on the plaque assay at a concentration of 100
micrograms/mL. The therapeutic efficacy of seven selected plants was demonstrated
by using a mouse HSV-1 infection assay, both the methanol extracts of the fruit
of Melaleuca leucadendron (Myrtaceae) and the pericarp of Nephelium lappaceum
(Sapindaceae) significantly prolonged the development of skin lesions and reduced
the mortality.
PMID- 10189949
TI - Effects of aqueous extracts from Quercus ilex L. root bark, Punica granatum L.
fruit peel and Artemisia herba-alba Asso leaves on ethanol-induced gastric damage
in rats.
AB - The gastroprotective effect of tannic acid and the aqueous extract of Quercus
ilex L. root bark, Punica granatum L. fruit peel and Artemisia herba-alba Asso
leaves was investigated in the rat against ethanol-induced damage. Tannic acid,
Q. ilex and P. granatum extracts gave 100% precipitation of ovine haemoglobin in
vitro, whereas A. herba-alba extract was devoid of any protein-binding property.
Oral administration of these plant extracts or tannic acid induced a significant
decrease in gastric lesions (47.7%-76%). The observed protection was more
pronounced when the test solution was given at the same time with ethanol, except
for Q. ilex extract. The acid content of the stomach was significantly increased
by P. granatum (368%) and A. herba-alba (251%) extracts prepared in ethanol. It
is suggested that monomeric and polymeric polyphenols can strengthen the gastric
mucosal barrier.
PMID- 10189950
TI - Effects of a purified fraction from Echeveria gibbiflora aqueous crude extract on
guinea-pig spermatozoa.
AB - Guinea-pig spermatozoa in the presence of a purified fraction from Echeveria
gibbiflora aqueous crude extract suffer a hypotonic-like effect. The phenomena
exhibited included a distension of the plasma membrane over the acrosome region,
inducing the formation of a huge 'head-bubble'. The agglutination effect was so
enhanced that instead of inducing sperm clusters, it produced cane-like 'stalk'
structures. The immobilizing activity was induced instantaneously after the
addition of the purified fraction. At electron microscope level it was possible
to observe a heavy amount of electron dense material of the purified fraction
embedded or intercalated along the plasma membrane. It was also possible to
corroborate the dispersion of the acrosomal content and the disappearance of the
external acrosome membrane. The purified fraction induced loosening of the plasma
membrane all along the sperm cell, however, the distension of the membrane was
only produced in the apical portion of the sperm head and not in the post
equatorial region. The results suggest that the plant may yield a compound
suitable for use as a vaginal barrier or male contraceptive agent.
PMID- 10189951
TI - Asiaticoside-induced elevation of antioxidant levels in healing wounds.
AB - Asiaticoside derived from the plant Centella asiatica is known to possess good
wound healing activity. Enhanced healing activity has been attributed to
increased collagen formation and angiogenesis. Since antioxidants have been
reported to play a significant role in the wound healing process we studied the
effect of asiaticoside on the levels of certain antioxidants in the wound so as
to explore the possible involvement of such a mechanism in the asiaticoside
induced wound healing. Asiaticoside application (0.2%, topical) twice daily for 7
days to excision-type cutaneous wounds in rats led to increased enzymatic and non
enzymatic antioxidants, namely superoxide dismutase (35%), catalase (67%),
glutathione peroxidase (49%), vitamin E (77%) and ascorbic acid (36%) in newly
formed tissues. It also resulted in a several fold decrease in lipid peroxide
levels (69%) as measured in terms of thiobarbituric acid reactive substance.
However, continued application for 14 days showed no significant difference in
these antioxidants compared with their values in vehicle treated wound tissue. It
appears from the present study that asiaticosides enhanced induction of
antioxidant levels at an initial stage of healing which may be an important
contributory factor in the healing properties of this substance.
PMID- 10189952
TI - Uterine muscle reactivity to repeated administration and phytochemistry of the
leaf and seed extracts of Piper guineense.
AB - The leaf and seed of Piper guineense were separately extracted and the effects of
repeated treatments on rat uterine contractions and their chemical composition
were investigated. Repeated treatments with the extracts enhanced spontaneous
uterine muscle contractions in a dose related pattern for up to 14 days which was
followed by a marked decrease in uterine response in those treated for 30 days.
Similarly, the pretreatment with the extracts maximally enhanced oxytocin induced
uterine contraction in those rats treated for 3 days, this was followed by a
gradual reversal of the effect when treatment was repeated for up to 14 days.
This enhanced uterine contraction was inhibited following treatment for 30 days.
In a further study, treatment with the extracts induced a significant increase in
the uterine weight similar to that seen with oestradiol. It is therefore
concluded that the leaf and seed extracts of Piper guineense possess oestrogenic
and oxytocic properties which might justify their usage in Nigerian traditional
medicine.
PMID- 10189954
TI - Immunomodulatory effect of Achyrocline satureioides (LAM.) D.C. aqueous extracts.
AB - The immunomodulatory activity of aqueous extract from Achyrocline satureioides,
prepared using heating, was investigated with a mitogen-induced cell
proliferation assay and IL-2 secretion in BALB/c mice. The results showed a
slightly immunosuppressive activity.
PMID- 10189953
TI - Non-ginsenoside nicotinic activity in ginseng species.
AB - Amongst the many different therapeutic applications of ginseng are beneficial
effects on age-related cognitive impairments. Ageing in the brain is associated
with a loss of nicotinic receptor binding and receptor stimulation increases
binding. Stimulation of the CNS (central nervous system) nicotinic receptor is
considered to be beneficial in relation to symptomatic treatment and
neuroprotection in age-associated cognitive disorders which involve a further
receptor loss. We assessed Panax ginseng, Panax quinquefolium and several
chemical constituents of these plants for nicotinic activity based on
displacement of 3H-(-)nicotine from human brain cerebral cortex membranes in
vitro. Dose-dependent displacement was evident in crude ethanol extracts of Panax
ginseng and Panax quinquefolium. Assay of an extract of Panax ginseng showed the
plant to have affinity for both the nicotinic receptor, and to a lesser extent
the muscarinic receptor (IC50 2.12 mg/mL and 5.25 mg/mL respectively). Activity
was largely conserved after the extraction of choline and other water soluble
quaternary ammonium compounds (QAC), indicating that the activity of the plant
extracts was not due to choline. Displacement binding assay of some purified
chemical constituents, including a number of ginsenosides, showed that these were
not primarily responsible for Panax activity. The active chemical constituent has
yet to be identified, but the demonstrated nicotinic activity of ginseng warrants
further investigation with reference to therapeutic activity in age-related
conditions such as dementia.
PMID- 10189955
TI - Antimicrobial spectrum of Alchornea cordifolia leaf extract.
AB - The 50% aqueous ethanol extract of Alchornea cordifolia (Schum and Thonn) Muell.
Arg. leaf was screened for activity against 74 microbial strains representing
aerobic, facultative and anaerobic bacteria as well as fungi. The panel of test
strains included organisms from culture collections as well as clinical and
environmental isolates. A concentration of 5 mg/mL of extract inhibited 36.5% of
the isolates and 95.9% were inhibited by a concentration of 20 mg/mL. Only three
strains, all filamentous fungi, were not susceptible to 40 mg/mL of the extract,
the highest concentration tested. The extract showed the best activity against
gram-positive bacteria and yeasts with inhibitory concentrations against these
organisms being under 5 mg/mL. The results demonstrate that the A. cordifolia
extract has a very broad spectrum of activity and suggests that it may be useful
in the treatment of various microbial infections.
PMID- 10189956
TI - Studies on the antibacterial potential of Cryptostegia grandiflora R. Br.
(Asclepiadaceae) extract.
AB - Different extracts of Cryptostegia grandiflora (Roxb) Rbr. leaves were
investigated for their antibacterial potential against Pseudomonus cepacia NCIM
2106, Bacillus megatorium NCIM-2087, Staphylococcus aureus NCIM-2492, Escherichia
coli NCIM-2345, Bacillus subtilis NCIM-2349 and Bacillus coagulans NCIM 2323.
Almost all the extracts produced significant antibacterial activity against all
the microorganisms being tested and the effect so produced was comparable to the
standard antibiotic, tetracycline hydrochloride. The petroleum ether (60 degrees
80 degrees C) extract showed maximum efficacy.
PMID- 10189957
TI - Antiinflammatory activity of extracts of Biophytum sensitivum in carrageenin
induced rat paw oedema.
AB - The antiinflammatory activity of aqueous and methanol extracts of aerial parts,
an aqueous extract of roots as well as ultrafiltration fractions of a methanol
extract of roots of Biophytum sensitivum were evaluated in the carrageenin
induced rat paw oedema model. All the extracts except the methanol extract of
aerial parts exhibited antiinflammatory activity, but inhibition of oedema was
found to be maximum with aqueous extracts.
PMID- 10189958
TI - Analgesic, antiinflammatory and hypoglycaemic activities of Sida cordifolia.
AB - Sida cordifolia extracts of the aerial and root parts showed good analgesic,
antiinflammatory and hypoglycaemic activities. The ethyl acetate (EA) extract of
root (SCR-E) showed comparable antiinflammatory activity with indomethacin and
possessed significantly higher activity when compared with that of the methanol
extract of the root part (SCR-M). The ethyl acetate extract of both root and
aerial parts of Sida cordifolia (SCR-E and SCA-E) showed very good central and
peripheral analgesic activities at a dose of 600 mg/kg. The methanol extract of
root (SCR-M) was found to possess significant hypoglycaemic activity.
PMID- 10189959
TI - Topical antiinflammatory activity of phytosterols isolated from Eryngium foetidum
on chronic and acute inflammation models.
AB - Eryngium foetidum L. (Apiaceae) is a Caribbean endemic plant, used in folk
medicine for the treatment of several antiinflammatory disorders. A preliminary
phytochemical study showed that the hexane extract is rich in terpenic compounds.
Chromatographic fractionation of this extract yielded: alpha-cholesterol,
brassicasterol, campesterol, stigmasterol (as the main component, 95%)
clerosterol, beta-sitosterol, delta 5-avenasterol, delta (5)24-stigmastadienol
and delta 7-avenasterol. The topical antiinflammatory activity of the hexane
extract and of stigmasterol was evaluated by auricular oedema, induced by 12-0
tetradecanoylphorbol acetate (TPA), in the mouse, using single and multiple
applications of the phlogistic agent. Both reduced the oedema in a similar
proportion in the two model assays (acute and chronic). Meloperoxidase activity
was strongly reduced by both the extract and the compound, in the acute but not
the chronic model. These results indicate that the leaves of Eryngium foetidum L
may be effective against topical inflammation processes. Stigmasterol also exerts
a significant topical antiinflammatory activity although it cannot be considered
to be a major antiinflammatory agent, therefore other bioactive components are
probably involved in the activity of the hexane extract.
PMID- 10189960
TI - Prolonged murine genotoxic effects of crude extracted from neem.
AB - Oral administration of a crude ethanol extract of the leaves of neem (Azadirachta
indica A juss) to adult Swiss albino mice for 7 days at 5 mg, 10 mg or 20 mg/10 g
bw/day significantly increased the incidence of structural and mitosis disruptive
changes in metaphase chromosomes of bone marrow cells on days 8, 15 and 35th of
observation. It is proposed that one or other of the many constituents of the
extract, along with genera free radicals, interfered with DNA to yield chromosome
strand breakage or produced spindle disturbances, inducing belated genotoxic
effects.
PMID- 10189961
TI - Cardiosensor mice and transcriptional subdomains of the vertebrate heart.
AB - Differential regulation of cardiac gene expression in vertebrates has been
extensively documented in the context of atrial and ventricular morphogenesis.
Recent data, largely from the analysis of transgene and endogenous gene
expression patterns, have revealed transcriptional differences between left and
right cardiac chambers which suggest that the heart is composed of a series of
distinct transcriptional domains. Such phenomena provide regional markers
(cardiosensors) for the fine analysis of normal and abnormal heart development.
Regional subdivisions and transcriptional heterogeneity within the myocardium
emerge in response to patterning of the precardiac mesoderm and early heart tube
on the anterior-posterior axis, and to embryonic left-right signals which dictate
the direction of cardiac looping. Several families of transcription factors have
been characterized which may be implicated in the regionalization of myocardial
gene expression.
PMID- 10189962
TI - HAND proteins: molecular mediators of cardiac development and congenital heart
disease.
AB - Congenital heart defects are the clinical manifestation of anomalies in embryonic
cardiac development. Such defects occur in distinct regions or chambers of the
heart. A molecular framework in which to consider cardiac development and
congenital heart disease in a segmental fashion has begun to emerge. dHAND and
eHAND are two related basic helix-loop-helix transcription factors that are
expressed in a complementary fashion in the developing right and left ventricles,
respectively. They are also expressed in the neural crest-derived cardiac outflow
tract and aortic arch arteries. Targeted mutations of dHAND and eHAND in mice
have revealed novel pathways of organogenesis in mesodermal and neural crest
derivatives. dHAND mutants exhibit hypoplasia of the right ventricle, branchial
arches, and aortic arch arteries. The distinct nature of cardiac defects in dHAND
mutants provides an entry into dissecting molecular pathways governing
morphogenesis of specific components of the heart. Congenital heart disease is
considered as a defect in segmental development of the heart and the role of
dHAND and eHAND in regulating such developmental pathways in normal and abnormal
cardiogenesis is examined.
PMID- 10189963
TI - Conducting the embryonic heart: orchestrating development of specialized cardiac
tissues.
AB - The heterogeneous tissues of the pacemaking and conduction system comprise the
"smart components" of the heart, responsible for setting, maintaining, and
coordinating the rhythmic pumping of cardiac muscle. Over the last few years, a
wealth of new information has been collected about the unique genetic and
phenotypic characteristics expressed by these tissues during cardiac
morphogenesis. More recently, genetically modified viruses, mutational analysis,
and targeted transgenesis have enabled even more precise resolution of the
relationships between cell fate, gene expression, and differentiation of
specialized function within developing myocardium. While some information
provided by these newer approaches has supported conventional wisdom, some fresh
and unexpected perspectives have also emerged. In particular, there is mounting
evidence that extracardiac populations of cells migrating into the tubular heart
have important morphogenetic roles in the inductive pattering and functional
integration of the developing conduction system.
PMID- 10189964
TI - Gq signaling in cardiac adaptation and maladaptation.
AB - Accumulating evidence suggests that cardiac responses to a number of circulating
or locally released humoral factors contribute to adaptive responses after
hemodynamic stress or myocardial injury. In particular, hormones such as
angiotensin II, endothelin 1, norepinephrine and prostaglandin F2 alpha which
bind to and activate cardiomyocyte membrane receptors coupled to the Gq class of
GTP binding proteins have been implicated in the development and ultimate
decompensation of cardiac hypertrophy. Herein we summarize recent developments in
cultured cardiomyocyte and transgenic mouse systems which are defining the
phenotypes resulting from Gq signaling events in cardiomyocytes, and which are
elucidating the critical downstream mediators. Postulated roles for protein
kinase C, p38 MAP kinase and jun-N terminal kinase are discussed in relation to
Gq-mediated cardiomyocyte hypertrophy and apoptotic signaling. The evidence to
date suggests that molecular targeting of Gq or its effectors has the potential
to modify cardiac adaptive and maladaptive responses to stress or injury.
PMID- 10189965
TI - Negative regulation of inflammation by Fas ligand expression on the vascular
endothelium.
AB - It is generally believed that the vascular endothelium serves as a barrier to
inflammation by providing a nonadherent surface to leukocytes. Recently, we
reported that vascular endothelial cells (ECs) express Fas ligand, which
functions to actively inhibit inflammation by inducing apoptosis in Fas-bearing
leukocytes. The inflammatory cytokine TNF alpha downregulates Fas ligand
expression with an accompanying decrease in EC cytotoxicity toward Fas-bearing
cells in co-culture. Endothelial Fas ligand expression in arteries is also
downregulated by the local administration of TNF alpha, and this correlates with
robust mononuclear cell infiltration of the subendothelial space. This TNF alpha
induced mononuclear cell infiltration is inhibited by pre-infecting the
endothelium with a replication-defective adenovirus that constitutively expresses
Fas ligand. Under these conditions, adherent leukocytes undergo apoptosis rather
than extravasation. These findings suggest that Fas ligand expression on the
vascular endothelium functions to inhibit inflammatory responses that are often
associated with vascular disorders.
PMID- 10189966
TI - Proteolytically activated receptor-3. A member of an emerging gene family of
protease receptors expressed on vascular endothelial cells and platelets.
AB - Macromolecular assembly and generation of serine proteases on cellular surfaces
is critically involved in regulation of hemostatic, inflammatory, or fibrinolytic
pathways. The concept that a number of these serine proteases may effect cellular
activation and proliferative responses has engendered an emerging paradigm
focusing on the molecular mechanisms regulating cellular/protease interactions.
Previous data suggest that some of these cellular responses are mediated by a
novel class of G protein-coupled proteolytically activated receptors.
Proteolytically activated receptor-3 (PAR-3) is the third member of this rapidly
emerging gene family, all three of which (PAR-1, PAR-2, PAR-3) are known to co
cluster in the human genome, and are expressed on vascular endothelial cells,
cells which critically regulate the hemostatic repertoire. This review will focus
on the genetics of these receptors (emphasizing recent advances in the
identification and characterization of PAR-3), review known structure/function
similarities, and outline potential links in regulation of the hemostatic
response by protease generation on the endothelial cell surface.
PMID- 10189967
TI - Homocysteine and hypomethylation. A novel link to vascular disease.
AB - A mild elevation in serum homocysteine levels is an independent risk factor for
arteriosclerosis and venous thrombosis. Despite the clinical significance of
homocysteine, however, the molecular mechanisms of homocysteine-induced
arteriosclerosis have not been completely elucidated. This lack of understanding
is due in large part to the excessively high concentrations of homocysteine
(greater than 1 mM) used in experiments. Many of homocysteine's effects have been
attributed to its prooxidant activity, which is implicated as the mechanism
through which it inhibits production of endothelium-derived relaxing factor and
activates quiescent vascular smooth muscle cells. We have found that homocysteine
at 10 to 50 microM (but not cysteine) inhibits progression of the vascular
endothelial cell cycle at or before the G1-S junction. This inhibition appears to
be mediated by decreases in the carboxyl methylation, membrane association, and
activity of p21ras--a major G1 regulator. Homocysteine may play an important role
in promoting arteriosclerosis by inducing endothelial dysfunction, by inhibiting
endothelial cell regeneration, and by directly activating quiescent vascular
smooth muscle cells.
PMID- 10189968
TI - Expression of the ryanodine receptor type 3 in skeletal muscle. A new partner in
excitation-contraction coupling?
AB - Mobilization of Ca2+ from the endoplasmic reticulum (ER) is mediated by two
related groups of Ca2+ release channels, the inositol 1,4,5 trisphosphate (InsP3)
receptors and the ryanodine receptors. The InsP3 receptors have been studied in a
large number of cells where they regulate many different activities upon
stimulation with a variety of agonists. Ryanodine receptors have been essentially
studied with respect to their role in regulating muscle contraction in both
cardiac and skeletal muscles. In the recent years, InsP3 receptors and ryanodine
receptors have been found to be co-expressed in neurons and other cell types,
including smooth muscle cells. This emerging picture reveals that within one cell
different combinations of two or more isoforms of Ca2+ release channels (i.e.,
multiple InsP3 receptors and/or ryanodine receptors) can be expressed at the same
time. New data on the expression of two isoforms of ryanodine receptors in
developing skeletal muscles or in specialized adult muscles have provided initial
ground to test the hypothesis that combinations of various Ca2+ release channels
may be relevant to adapt the modality of Ca2+ release to regulation of specific
cellular functions.
PMID- 10189969
TI - Age and the role of symptomatology in readiness to quit smoking.
AB - To develop effective age-appropriate strategies for smoking cessation, it is
important to understand factors associated with readiness to quit smoking. This
article presents results from an analysis of the role of symptomatology in the
decisions to quit smoking among three age groups (18-34, 35-54, and > or = 55
years) from a larger sample of smokers in a managed-care setting. Two measures of
readiness to quit smoking were used: stages of change and intention to stop.
Using ordinal logistic regression, we found that smokers in the middle and oldest
age groups who had experienced at least three of five symptoms in the previous 2
weeks were more likely to be in higher stages of readiness. Regardless of age,
smokers who attributed symptoms to smoking were more motivated to try to quit,
whereas those who attributed symptoms to aging were less likely to intend to stop
smoking. Findings from this study indicate a symptom-based approach to smoking
cessation may be a useful strategy, especially in provider-based interventions.
PMID- 10189970
TI - Optimizing the cost-effectiveness of alcohol treatment: a rationale for extended
case monitoring.
AB - There has been much research on and debate about the appropriate length of acute
treatment for alcohol problems. In the United States, the lengthy and costly
treatment programs of only a few years ago have been supplanted by ever-shorter
and less intensive protocols, with little evidence that this trend will end soon.
In this paper, we argue that, because of the chronic, recurrent nature of alcohol
problems, an optimal system for delivering treatment services to alcoholics needs
to focus on long-term engagement with clients. There is evidence from studies on
research reactivity and telephone follow-up protocols that a low-intensity long
term protocol for maintaining contact with clients over time spans measured in
years may result in better long-term clinical outcomes and reduced long-term
health care utilization and costs. We describe a flexible long-term low-intensity
follow-up protocol for alcohol abusers we call "case monitoring." This protocol
is specifically designed to minimize long-term health-care use. We predict that
such an intervention should be especially efficacious for women, persons with
comorbid Axis I disorders, and persons lower in sociopathy. The design of a study
to determine the clinical and health service effects of this intervention is also
described.
PMID- 10189971
TI - Substance refusal skills in a population of adolescents diagnosed with conduct
disorder and substance abuse.
AB - The present study examined substance refusal skills of 44 conduct-disordered male
adolescents. Fifty percent of these adolescents were dually diagnosed with
substance abuse/dependence. Substance refusal skills were assessed utilizing a
role-play test that consisted of four interpersonal scenarios in which a
confederate prompted youths to engage in illicit drug and alcohol activity. The
test demonstrated adequate interrater agreement and validity. Overall skill in
refusing alcohol was positively related to adolescents' perceptions of belonging
and attention, and overall skill in refusing illicit drugs was positively related
to school performance and social competence. Contrary to expectations, substance
refusal skills of dually diagnosed adolescents were comparable to their non
substance-abusing counterparts. Clinical implications of this study are
discussed.
PMID- 10189972
TI - Modification of the cognitive model for bulimia via path analysis on a Brazilian
adolescent sample.
AB - Eating disturbances in middle-class Brazilian adolescents attending three high
schools (one Military, two Private schools) were investigated. Participants from
both Private schools were similar to U.S. samples on the EAT-26. Path analysis on
the Private schools revealed the following. Higher body weight leads to weight
concerns most strongly through greater discrepancy from the ideal, but it also
leads directly to weight concern. Thus, both the reality of being heavier and the
perception that one is larger than ideal (which could be due to being heavier
and/or having a thin ideal) contribute to weight concern. Greater weight concern
is associated most directly with lower self-esteem, which in turn is associated
with endorsing greater importance of weight and shape. Importance of weight and
shape contributes most powerfully to eating pathology through dieting, but this
variable has a modest direct effect as well. These paths were not significant for
the Military school sample in which participants reported lower levels of weight
concern, dieting, body dissatisfaction, and a larger ideal figure. However, the
Military sample rated importance of weight and shape as high as did Private
school participants. The results provide support for variables identified as
important in the cognitive model of bulimia and suggest the model may be enhanced
by including body weight and one's perceived ideal body shape as additional
variables.
PMID- 10189973
TI - Inhalant use among antisocial youth: prevalence and correlates.
AB - The current (2.9%), annual (19.6%), and lifetime (34.3%) prevalence of inhalant
use among 475 youth (M age = 15.5; SD = 1.5; 87.4% male) on probation in a
western state of the United States was assessed. Inhalant users reported
significantly less family support and cohesiveness and lower self-esteem, and
significantly more lifetime thoughts of suicide and suicide attempts,
neighborhood gang activity, peer and parental substance abuse, intentions to
engage in illegal behavior, substance-related criminality, and substance abuse
than did nonusers. Ethnicity, self-esteem, suicidality, number of substance-using
peers, and extent of substance-related criminality significantly discriminated
inhalant users from nonusers in a logistic regression analysis. Multiple linear
regression analyses indicated that age, perceived school ability, age at
initiation of alcohol use, self-esteem, and substance-related criminality
significantly predicted age at onset of inhalant use (R2 = .30). Age at
initiation of inhalant use, gang membership, truancy, and substance-related
criminality significantly predicted lifetime frequency of inhalant use (R2 =
.20). Study findings indicate that inhalant-using delinquents evidence
significantly greater antisocial attitudes, personal and familial dysfunction,
and substance abuse, than do their non-inhalant-using counterparts.
PMID- 10189974
TI - Weight control smoking among sedentary women.
AB - This study examined characteristics associated with weight control smoking among
281 sedentary women enrolled in a smoking cessation trial. A series of regression
models were developed to identify predictors of weight control smoking as
measured by the Smoking Situations Questionnaire. Predictor variables included
demographic variables, dietary intake, weight gain following previous quit
attempts, dietary restraint, self-efficacy for weight management, smoking
behavior, exercise behavior, negative affect and psychological constructs
relevant to smoking cessation, and exercise adoption. In the final predictor
model, anticipation of weight gain in the current quit attempt, higher dietary
restraint, younger age, greater Fagerstrom scores, greater number of pounds
gained in previous quit attempts, and lower levels of self-efficacy to manage
weight in negative affect situations were associated with smoking for weight
control. Treatment implications for women who smoke for weight control reasons
are discussed.
PMID- 10189975
TI - The relationship among self-efficacy expectancies, severity of alcohol abuse, and
psychological benefits from drinking.
AB - The aim of the study is to examine the relationship among self-efficacy
expectancies and two important clinical aspects of alcohol abuse, namely the
severity of abuse and strength of the perceived psychological benefits from
drinking. The self-efficacy expectancies were measured by the Situational
Confidence Questionnaire (Annis, 1984) in a group of alcoholic men (N = 203). A
systematic and significant relationship was identified between the subjects'
confidence in coping with high-risk factors for heavy drinking and their severity
of abuse. The subjects' level of confidence decreased proportionally with an
increase in their abuse. Furthermore, the subjects' perceived psychological
benefits from drinking covaried with their self-efficacy. A significant
association was found between lower self-efficacy scores and experiencing great
psychological benefits from drinking such as improved social skills, less
depression and tension, and improved cognition. A combination of the two
variables, severity of abuse and strength of perceived benefits, shows a
systematic and differentiated picture among the subgroups. Clinical implications
based on the results are presented.
PMID- 10189976
TI - Prosocial coping and substance use during pregnancy.
AB - In structured interviews of pregnant inner-city residents, 38 substance users
reported more current liking of drugs and polysubstance use, disengagement
coping, depressive symptoms, negative affect, and antisocial behavior than did 45
nonusers. During videotaped interviews, trained observers coded less warmth and
less prosocial information exchange (e.g., self-disclosure, question asking)
among users. Factor analysis of measures of coping and its concomitants yielded a
three-factor (prosocial, antisocial, asocial) solution, with asocial and
antisocial coping predominating among substance users. These results suggest that
coping has emotional, social, and cognitive elements. This study is the first to
demonstrate an association between a substance-using lifestyle and limited
prosocial information exchange.
PMID- 10189978
TI - Smoke constituent exposure and stage of change in black and white women cigarette
smokers.
AB - Differences in smoke constituent exposure by ethnicity and menthol preference and
differences in decisional balance and habit strength by stage of change,
ethnicity, and menthol preference were examined in this 2-factor study design.
Ninety-five women, half of whom were Black and half of who smoked menthol
cigarettes, participated in a cigarette smoking bout in the Clinical Research
Center. Measures of smoking topography, plasma cotinine and nicotine, and expired
carbon monoxide were obtained in addition to self-report of the pros and cons of
smoking, time to first cigarette, and smoking history. Black women smoked
significantly fewer cigarettes per day, but had higher cotinine levels compared
to White women. Menthol smokers (n = 49) had significantly larger puff volumes,
higher cotinine levels, and shorter time to first cigarette compared to
nonmenthol smokers (n = 46). Precontemplators (n = 44) were significantly lower
on beliefs about the negative aspects of smoking compared to contemplators and
those in preparation stage. Black women, all stages combined, had higher negative
beliefs about smoking than did White women. Implications for assessment of
smoking patterns and intervention are discussed.
PMID- 10189977
TI - Fluoxetine versus placebo for the marijuana use of depressed alcoholics.
AB - The aim of this analysis was to evaluate the efficacy of the SSRI antidepressant
fluoxetine versus placebo for the marijuana use of depressed alcoholics. There
are no previous reports involving and SSRI antidepressant for marijuana abuse.
This analysis involved a subsample of 22 depressed alcoholic marijuana users out
of a total of 51 depressed alcoholics. The entire sample was involved in a 12
week double-blind, placebo-controlled study evaluating the efficacy of fluoxetine
versus placebo in depressed alcoholics. During the course of the trial, the
cumulative number of marijuana cigarettes used was almost 20 times as high in the
placebo group as in the fluoxetine group. Also, the number of days of marijuana
use during the study was five times higher in the placebo group than in the
fluoxetine group. These data suggest efficacy for fluoxetine in decreasing
marijuana use of depressed alcoholics.
PMID- 10189979
TI - Familial risk for alcoholism and hangover symptoms.
AB - Previous work suggests sons of alcoholics (SOAs) report greater hangover symptoms
than do sons of nonalcoholics (SONAs) (Newlin & Pretorious, 1990; McCaul,
Turkkan, Svilis, & Bigelow, 1991). This study sought to replicate this work and
examine the relation between personality risk for alcoholism and hangover. Twenty
SOAs and 20 SONAs completed the MacAndrew scale as an index of personality risk
for alcoholism. They also completed the McCaul et al. (1991) and Newlin and
Pretorious (1990) assessments of hangover after consuming a placebo in one
session and alcohol (0.5 g/kg) in two subsequent consecutive sessions. The
MacAndrew scale did not covary with hangover. Data revealed main effects for
familial risk for both hangover questionnaires. SOAs reported significantly
greater hangover symptoms than did SONAs. Individuals at elevated familial risk
for alcoholism reportedly experienced more acute withdrawal and hangover, which
might contribute to the development of problem drinking.
PMID- 10189980
TI - Effects of menstrual phase on reactivity to nicotine.
AB - The possible impact of menstrual phase upon reactivity to nicotine was
investigated in 12 healthy women smokers. Controlled doses of nicotine were
administered via an intranasal aerosol delivery device to overnight-deprived
women smokers in four hormonally verified menstrual phases. Physiological,
biochemical, and subjective measures were collected. Cycle-related symptomatology
differed significantly across phase, with lowest values during the mid-follicular
phase. No significant differences were found for baseline variables, including
withdrawal measures. Nicotine increment was stable across phase, confirming
reliability of the dosing method. No significant menstrual phase differences were
found for physiological, subjective, or biochemical responses to nicotine.
Pending investigations conducted over longer intervals, in a wider variety of
subjects; findings suggest that for this type of study, complex strategies to
control for menstrual-cycle phase effects may be unnecessary.
PMID- 10189981
TI - Situational determinants of alcohol abuse among Caucasian and African-American
college students.
AB - The present study examined gender, race, and binge status differences in alcohol
consumption among Caucasian and African-American college students as well as
situational differences as qualified by the race of binge drinkers. A
confidential questionnaire was voluntarily completed by Caucasians (n = 102) and
African-Americans (n = 81) at a medium-sized regional university. The data
analysis revealed a significant gender effect on alcohol consumption, with men
consuming more alcohol than women. There was no significant main effect of race
on alcohol consumption. In addition, Caucasian binge drinkers had significantly
higher interpersonal problem behavior scores than did binge-drinking African
Americans, and binge-drinking African-Americans had higher intrapersonal problem
behavior scores than did binge-drinking Caucasians.
PMID- 10189982
TI - Depressive symptoms and mentally ill chemical abusers' perception of the
treatment environment in residential settings.
AB - In assessing the socioenvironmental characteristics of psychiatric treatment
programs, researchers typically assume that their measurements are unaffected by
client characteristics. However, our analysis among mentally ill chemical abusers
in a therapeutic community and community residences found significant
associations between subscales of the Community Oriented Program Evaluation Scale
(COPES) and depressive symptoms, as measured by the CES-D, after 2, 6, and 12
months of treatment. Investigators of treatment environments should consider
depressive symptoms as a possible threat to the validity of their findings.
PMID- 10189983
TI - An evaluation of NicCheck I: a dipstick method for analyzing nicotine and its
metabolites.
AB - This study examined the reliability of a test strip for assessing urinary
nicotine and its metabolites. Urine samples from smokers were tested by two
independent raters using the NicCheck I test strips. Each rater compared the test
strip color to a five-color chart. Correlations between the rater's codings and
between the coding and other measures of nicotine consumption were examined.
Significant correlations were found between the two independent ratings of the
test strip color and between the codings and other measures of nicotine
consumption. This preliminary evaluation suggests that NicCheck I is sensitive to
differences in nicotine consumption.
PMID- 10189985
TI - Amphibian metamorphosis as a model for studying the developmental actions of
thyroid hormone.
AB - A salient feature of the thyroid hormones. L-thyroxine (T4) and triiodo-L
thyronine (T3), is the multiplicity of their physiological and biochemical
actions in a wide variety of vertebrates. Important among these is their profound
effects on postembryonic development. Analysis of their developmental action in
mammals is vitiated by the exposure of the developing foetus to a number of
maternal factors which do not allow one to specifically define the role of
thyroid hormone (TH) or that of other hormones and factors that modulate its
action. Amphibian metamorphosis is obligatorily dependent on TH which can
initiate all the diverse physiological manifestations of this postembryonic
developmental process (morphogenesis, cell death, re-structuring, etc.) in free
living embryos and larvae of most anurans. It is therefore an ideal model for
studying the mechanisms underlying the hormonal regulation of postembryonic
development. This article will first summarize the key features of metamorphosis
and its control by TH and other hormones. Emphasis will be laid on the important
role played by TH receptor (TR), in particular the phenomenon of TR gene
autoinduction, in initiating the developmental action of TH. Finally, it will be
argued that the findings on the control of amphibian metamorphosis enhance our
understanding of the regulation of postembryonic development by TH in mammals and
other vertebrate species.
PMID- 10189984
TI - History of alcohol or drug problems, current use of alcohol or marijuana, and
success in quitting smoking.
AB - Previous research suggests higher rates of smoking, and smoking cessation
failure, in alcohol- and drug-abusing populations. The present study examined the
relationship of alcohol/drug treatment history and current alcohol and marijuana
consumption with success in smoking cessation treatment in a smoking clinic
population. Participants were 199 smokers; 23% reported a history of alcohol/drug
problems, 12.6% reported a history of drug treatment, 78.7% reported alcohol use,
and 21.3% reported marijuana use during treatment. Results indicate no
significant differences in abstinence rates based on history of alcohol/drug
problem or treatment. Differences were found for any current alcohol use but not
for marijuana use. Both alcohol use at baseline and any alcohol use during
treatment predicted smoking at all follow-up points. Alcohol users had
significantly lower quit rates than did participants reporting no use. Neither
use of marijuana at baseline nor during treatment predicted outcome. These
findings suggest that even low to moderate levels of alcohol consumption during
smoking cessation may decrease treatment success.
PMID- 10189986
TI - [Clinicogenetic study of MEN1: recent physiopathological data and clinical
applications. Study Group of Multiple Endocrine Neoplasia (GENEM)].
AB - Multiple Endocrine Neoplasia type 1 (MEN1, OMIM 131100, Wermer syndrome) is
characterized by inherited predisposition to primary hyperparathyroidism,
endocrine pancreatic-duodenal, pituitary, adrenal glands tumors and benign and/or
malignant proliferations of diffuse neuroendocrine tumors in thymus and bronchi,
formerly defined as carcinoid tumors. Minor lesions have been observed in MEN1
patients such as cutaneous tumors (angiofibroma, lipoma, lentiginosis), thyroid
epithelioma and tumors of the central nervous system, mainly spinal ependymoma.
The MEN1 gene, a locus encompassing a 9 kb of genomic sequence contains 10 exons,
the first exon being untranslated. The protein encoded by this gene was called
menin and has been shown to contain two nuclear localization signals (NLS),
suggesting a major function in the nucleus. Germline MEN1 mutations have been
described in more than 150 families and are spread throughout the entire coding
sequence. More than 70% of the mutations alter one or both NLS and no genotype
phenotype correlations were found to date. The MEN1 gene seems to be involved in
a 20-30% of sporadic parathyroid and pancreatic/bronchic neuroendocrine tumors,
but less than 1% of pituitary sporadic tumors. Further knowledge on the
intracellular function of menin will be needed to understand the pathogenic
effect of truncating and missense mutations of this gene in the initiation of
endocrine cells tumorigenesis.
PMID- 10189987
TI - [Von Hippel-Lindau disease: recent genetic progress and patient management.
Francophone Study Group of von Hippel-Lindau Disease (GEFVH)].
AB - Von Hippel-Lindau (VHL) disease is an autosomal dominant disorder, predisposing
to the development of central nervous system (CNS) and retinal hemangioblastomas,
endolymphatic sac tumors, renal cell carcinoma and/or renal cysts,
pheochromocytomas, pancreatic cysts and/or tumors. Incidence of the disease is
1/36,000. CNS hemangioblastomas and renal cell carcinoma are the main causes of
death. The VHL gene, located on 3p25-26, is a tumor-suppressor gene which plays a
major role in regulation of VEGF expression. Germline mutations of the VHL gene
are identified in about 70-99% of the patients. Mutations associated with VHL
type 2 (with pheochromocytoma) are mainly missense mutations with hot-spot at
codon 167. Somatic mutations of the VHL gene are found in both sporadic central
nervous system hemangioblastomas and sporadic renal cell carcinoma. For
endocrinologists search for VHL disease (as for MEN) should be imperative in
presence of a patient with pheochromocytoma and neuroendocrine pancreatic tumor.
PMID- 10189988
TI - [Impact of recent oncogenetic progress on the management of high risk breast
cancer patients: the example of BRCA1 and BRCA2 genes].
AB - Evidence is mounting that hereditary breast cancers and sporadic cases harbor
distinct clinical and morphological patterns that are thought to be linked to
different natural histories. BRCA1-associated breast cancers appear as high
grade, poorly differentiated, highly proliferating, and frequently estrogen
receptor negative tumors. Surprisingly, despite these features usually associated
with a poor outlook, no decrease in the overall survival is observed in
hereditary cases. These elements may be of valuable help in the design of
strategies in the medical management of cancer prone individuals.
PMID- 10189989
TI - [Hereditary risks of breast cancer. Interaction of genetic factors and hormonal
factors].
AB - The association between risk of breast cancer and familial risk is well
documented. The first observation was described by Paul Broca around 1850 from
his own family. Germinal mutations have been estimated to account for 5 to 10% of
breast cancer cases. However, some questions remains unclear in this context of a
multifactorial disease. Even if the rise in breast cancer risk associated with
BRCAx mutations is well established, the place of a genetic factor among other
factors risks of breast cancer remains unclear. The interaction between genetic,
environmental and hormonal factors is an important problem. More particularly the
effect of oral contraceptives and hormonal replacement therapy in women with or
without hereditary susceptibility of breast cancer needs to be addressed.
PMID- 10189990
TI - [INSERM-FNCLCC collective expert's report. Recommendations for management of
women having a genetic risk of developing breast and/or ovarian cancer. National
Federation of Centers of the Fight Against Cancer].
AB - BACKGROUND: Almost 10% of breast and ovarian cancer are inherited, and the
majority are linked to BRCA1 and BRCA2 germline mutations. Despite the
uncertainty, consensus guidelines were defined to assist practitioners', and
patients' decisions about the health care decisions to be made. METHODOLOGY: The
Ad Hoc Committee consisted of 14 experts designated by the French National
Institute for Health and Medical Research. They all attended eleven workshops at
which a systematic analytical review of more than 3500 articles was carried out.
Five additional experts critically analyzed the first version of the report.
PROCESS: Two thresholds were defined on a probability scale giving the risk of
developing breast or ovarian cancer, to serve as a means of deciding as whether
an intervention is worthwhile. The first threshold is that above which an
intervention can be envisaged or recommended; the second is that under which an
intervention can be ruled out; between the two, the decision has to be made on a
each by case basis. SCREENING AND PREVENTIVE STRATEGIES ANALYZED: About breast
cancer: 1) hormonal interventions; 2) primary prevention (diet, family planning
and chemoprevention); 3) screening (breast self-examination, clinician breast
examination, tumor markers, imaging); 4) prophylactic mastectomy. About ovarian
cancer: 1) hormonal stimulation; 2) screening (clinical screening, ultrasound and
tumor markers); 3) prophylactic oophorectomy. MAIN CONCLUSIONS: With each
strategy the following points were dealt with: the information to be delivered to
the consultant, the procedure and the indications. The Committee's opinion about
BRCA mutation screening is that population-based or even large scale
implementation are not justified. The Committee feels that specific management is
indispensable and advocates the use of defined and evaluated procedures, and
involvement in clinical trials.
PMID- 10189992
TI - Neuromas and prominent corneal nerves without MEN 2B.
AB - PURPOSE: We studied a family composed of 2 members with the characteristic
phenotype of the MEN 2B and without RET protooncogene mutations in order to
determine whether they had multiple endocrine neoplasia associated with MEN 2B in
the 5-year follow-up. SUBJECTS AND METHODS: The family consisted of a 15 year old
female complaining of burning eyes, examined ophthalmologically in 1992 and her
mother and sister, who were examined later on in 1992. The proband and the mother
were affected with multiple mucosal neuromas and visible corneal nerves.
Pentagastrin-stimulated serum calcitonin levels, catecholamines, serum calcium
and phosphate levels were measured. Molecular genetic studies were performed on
the 2 affected members to look for the specific RET mutation seen in MEN 2B.
RESULTS: Endocrine neoplasia of the syndrome MEN 2B, medullary thyroid carcinoma,
pheochromocytoma and hyperparathyroidism, were ruled out in the first examination
and after 5-year follow-up. In the 2 cases no mutation at codon 918 for the RET
proto-oncogene was found. CONCLUSIONS: We consider that familial multiple mucosal
neuromas are a highly distinctive entity of MEN 2B.
PMID- 10189991
TI - Loss of imprinted genes and paternal SUR1 mutations lead to hyperinsulinism in
focal adenomatous hyperplasia.
AB - Two types of histopathological lesions, a focal adenomatous hyperplasia of islet
cells of the pancreas in about 30% of operated sporadic cases, and a diffuse form
can be observed in congenital hyperinsulinism, or Persistent Hyperinsulinemic
Hypoglycemia of Infancy (PHHI). In sporadic focal forms, specific losses of
maternal alleles (LOH) of the imprinted chromosomal region 11p15, restricted to
the hyperplastic area of the pancreas, were observed. Similar mechanisms are
observed in embryonal tumors and in the Beckwith-Wiedemann syndrome which is also
associated with neonatal but transient hyperinsulinism. However this region also
contains the sulfonylurea receptor (SUR1) gene and the inward rectifying
potassium channel subunit (KIR6.2) gene, involved in recessive familial forms of
PHHI, but not known to be imprinted. We now report somatic reduction to
hemizygosity or homozygosity of a paternal SUR1 constitutional heterozygous
mutation, in five patients with a focal form of PHHI. Thus this somatic event
(LOH) which leads both to b cell proliferation and to hyperinsulinism can be
considered as the somatic equivalent, restricted to a microscopic focal lesion,
of constitutional uniparental disomy associated with unmasking of a heterozygous
parental mutation leading to a somatic recessive disorder.
PMID- 10189993
TI - [The role of agglutination during bacterial infection].
PMID- 10189995
TI - [Vasoconstrictor responses of the tail artery in rats with regional arterial
hypotension].
PMID- 10189994
TI - [The role of guanylate cyclase and arachidonic acid metabolites in the regulation
of epithelium-dependent relaxation in the smooth muscle from the rat trachea].
PMID- 10189996
TI - [Functional characteristics of hematopoietic and stromal cells in various forms
of myelodysplastic syndrome].
PMID- 10189997
TI - [Metabolic and physiological characteristics of the immediate response of the
body to overheating].
PMID- 10189998
TI - [Monoamine level in the rat brain with MPTP-induced depressive syndrome].
PMID- 10189999
TI - [Electroacupuncture effect on the systemic hemodynamics in animals with
postinfarct cardiosclerosis].
PMID- 10190000
TI - [Bioelectrical activity in the sensorimotor cortex in rats with pain syndrome of
the spinal origin].
PMID- 10190001
TI - [Cytostatic-induced cell death in hypoplasia of the hematopoietic tissue].
PMID- 10190002
TI - [Effect of He-Ne laser irradiation on thrombocyte lipids].
PMID- 10190003
TI - [Epidermal growth factor receptors during endometrial adenomatosis].
PMID- 10190004
TI - [Effects of synthetic peptide fragments of beta2-glycoprotein-I on binding
antiphospholipid antibodies with cardiolipin].
PMID- 10190005
TI - [Thermostable hepatocyte growth factor and energy metabolism following partial
hepatectomy in rats].
PMID- 10190006
TI - [Central kappa1-opioid receptors and arrhythmogenesis mechanism].
PMID- 10190007
TI - [Vasopressin: secondary immune response and antigen-specific suppressants].
PMID- 10190008
TI - [Production of mediators enhancing antineoplastic cytostatic activity of bone
marrow cells by activated lymphocytes].
PMID- 10190009
TI - [Xymedon restores T-cell immune response inhibited by gamma-irradiation in vivo:
relation to Ca2+-ATPase and DNA-relaxing activity].
PMID- 10190011
TI - [Properties of microsomal liver membranes from senescence accelerated mice].
PMID- 10190010
TI - [Effects of hydroxysterols on expression of inflammatory cytokine genes and their
level in macrophages tolerant to endotoxin].
PMID- 10190012
TI - [Characteristics Ca2+-induced hyperpolarization in erythrocytes from patients
with tumors of various localization].
PMID- 10190013
TI - [Effects of repeated administration of Ebola virus preparations on dynamics of
immunologic parameters].
PMID- 10190014
TI - [Changes in activation marker expression by lymphocytes in patients with
infectious allergic myocarditis associated with disease progression].
PMID- 10190015
TI - [Effects of biotechnological cytochrome c on early postocclusion and reperfusion
arrhythmias].
PMID- 10190017
TI - [Cardiomyocyte chondriome ultrastructure after clinical death and in the
postresuscitation period in rats].
PMID- 10190016
TI - [Antidiphtheria activity of epidermal growth factor precursor fragment].
PMID- 10190018
TI - [Three-dimensional structure of myocardial filaments during cardiac insufficiency
caused by toxic allergic myocarditis].
PMID- 10190019
TI - [Extracellular and intracellular collagen resorption by smooth muscle cells
during uterine involution in postpartum period].
PMID- 10190020
TI - [Changes in morphology, cytoskeleton, and substrate dependence of proliferation
induced by transfection of the rat immortalized embryonal fibroblasts with human
papilloma E7 viral gene type 16].
PMID- 10190021
TI - [Comparative analysis of radiometric and autoradiographic methods for studies on
DNA-synthesizing cell activity in vitro].
PMID- 10190022
TI - [Evaluation of the thymus lymphocyte transmembrane potential during dexamethasone
induced apoptosis].
PMID- 10190023
TI - A comparative review of the structure and biosynthesis of thyroglobulin.
AB - Thyroglobulin, the major iodoglycoprotein of the thyroid (Mr 669 kDa) has a
sedimentation coefficient of 19 S and an isoelectric point (pI) of 4.4-4.7. The
protein has been isolated and purified from saline extracts of the gland of
several animal species, by methods such as ammonium sulfate fractionation, DEAE
cellulose chromatography and Sepharose 4B/6B gel-filtration. DEAE-cellulose
chromatography of thyroglobulin from many species, by linear gradient, yielded a
complex elution pattern, while camel thyroglobulin showed only a major and minor
peak. As an iodoprotein, the protein has 0.1-2.0% iodine. The amino acid and
iodoamino acid composition of thyroglobulins, in general, is similar. However, a
high thyroxine content (15 mol/mol protein) has been noted for buffalo species.
Asparagine or aspartic acid has been reported as the major N-terminal amino acid
for thyroglobulins of several animal species whereas glutamic acid is the sole N
terminal amino acid for buffalo thyroglobulin. As a glycoprotein, thyroglobulin
contains 8-10% total carbohydrate with galactose, mannose, fucose, N-acetyl
glucosamine and sialic acid residues. The carbohydrate in the protein is
distributed as two distinct units, A and B. In addition, human thyroglobulin has
carbohydrate unit C. The occurrence of sulfate and phosphate as Gal-3-SO4 and Man
6-PO4, respectively, has been reported in few species. The quaternary structure
of native thyroglobulin is comprised of two equal sized subunits of 330 kDa.
However, the protein appears to contain 4-8 non-identical units in few species.
The synthesis of thyroid hormones occurs in the matrix of the protein and is
regulated by pituitary thyrotropin. The role of tyrosine residues 5 and 130 in
thyroxine synthesis has been well documented.
PMID- 10190024
TI - In vitro effects of cadmium and DDVP (dichlorvos) on intestinal carbohydrase and
protease activities in freshwater teleosts.
AB - In vitro effects of cadmium (0.5-50 mg/l) and DDVP (0.2-100 mg/l) on the total
amylolytic, sucrase and protease activities of intestinal mucosa have been
studied for the first time in 11 freshwater teleosts. Total amylolytic activity
in burbot, crucian carp and common carp, sucrase activity in blue bream and total
proteolytic activity in burbot and pike were significantly decreased by cadmium
at 50 mg/l. DDVP (at 0.2 mg/l) caused a significant decrease in total proteolytic
activity in pike but had no effect on either protease or carbohydrase activities
in other fish species.
PMID- 10190025
TI - Effects of some beta-carboline alkaloids on intact Trypanosoma cruzi
epimastigotes.
AB - Several beta-carboline (9H-pyrido-[3,4-b]-indole) alkaloids were evaluated for in
vitro trypanosomicidal activity against Trypanosoma cruzi epimastigotes belonging
to two different strains (Tulahuen and LQ) showing different sensitivity to
nifurtimox. Important differences were observed in the susceptibility of the
parasites to these natural substances, with the relatively nifurtimox-resistant
LQ strain showing greater sensitivity to the beta-carbolines. Respiratory chain
inhibition appears to be a possible determinant of the trypanosomicidal activity
of these compounds.
PMID- 10190026
TI - Effects of inorganic mercury on the respiration and the swimming activity of
shrimp larvae, Pandalus borealis.
AB - In order to test the sensitivity of respiration (physiological and potential) to
mercury (Hg) contamination, larval shrimp Pandalus borealis were exposed to
inorganic Hg (0-160 ppb) for 27 h in the laboratory. Oxygen consumption rates
(RO2), potential respiration (determined by respiratory electron transfer system
activity, ETSA), protein content, and swimming activity for zoeae III and zoeae V
stages were measured. For both zoeae stages, ETSA and protein content remained
constant after 27 h exposure to 160 ppb Hg whereas RO2 and swimming activity
decreased. This study revealed the impact of different Hg levels and different
exposure times on RO2 of shrimp larvae. After 10 h exposure to 160 ppb Hg, the
RO2 decreased by 43 and 49% in zoeae III and zoeae V stages, respectively.
Exposure time of 27 h to 80 ppb Hg and higher, induced paralysis in nearly 100%
larvae. Surprisingly, the paralysed larvae displayed almost 50% of the control's
RO2. The results showed that Hg disturbs a part of the respiration process
without modifying the maximum activity of the enzymes involved in the ETSA assay.
Therefore, the ETSA assay can not be used as a sublethal bioanalytic probe to
detect Hg in short-term exposures. The decline of the RO2/ETSA ratios reported
here, indicates an inability of contaminated larvae to adapt their metabolism to
physiological stress caused by Hg.
PMID- 10190027
TI - Fatty acid alterations caused by PCBs (Aroclor 1242) and copper in adipose tissue
around lymph nodes of mink.
AB - Fatty acid composition was determined in adipose tissue surrounding the
mesenteric lymph nodes of mink (Mustela vison) exposed to polychlorinated
biphenyls (PCBs: 1 mg Aroclor 1242 in food day-1 for 28 days) and/or copper (62
mg kg-1 food). These specific adipose tissues are known to have functional
relationships with lymphocytes, and proliferation of cultured lymphocytes is
influenced by the quality of fatty acids available in media. In six experimental
groups the diet was based on freshwater fish, and in two groups it was based on
marine fish. These basal diets differed in terms of fatty acid composition and
content of fat-soluble vitamins A1 and E. The fatty acid composition of membrane
phospholipids (PL) responded to PCBs more than that of triacylglycerols (TG). The
effects of copper were small. In female minks fed a diet of freshwater fish, the
proportion of highly unsaturated fatty acids in PL decreased by 5 wt.% due to
PCBs, and the acids seemed to be replaced by monounsaturated fatty acids (9 wt.%
increase of total). This decrease of highly unsaturated fatty acids in PL was
milder in minks on the marine fish diet rich in fat-soluble vitamins. In TG of
minks on the marine diet, however, PCBs decreased the proportion of
docosahexaenoic acid (22:6n-3). The possibility that these alterations in the
fatty acid metabolism of adipose tissue supporting the lymph nodes affect immune
function during PCB exposure should be studied further. Interestingly, the
quality of the fish diet affected the magnitude of the alterations. The fatty
acid responses may also differ between males and females.
PMID- 10190028
TI - Effect of thyroid hormone on concentrations of plasma calcitonin in broiler
chicks.
AB - The purpose of these studies was to determine the effect of thyroidectomy (Tx),
and thyroid hormone (T3/T4) treatment on concentrations of plasma CT in chicks.
In addition, the turnover of CT in Tx- and T3/T4-treated chicks was estimated
using a novel nonradioactive salmon CT preparation. One-week-old broiler chicks
(Gallus domesticus) (n = 75) were divided into three groups. Group I was sham
injected daily (i.m. saline), Group II was injected with 50 micrograms/day of
T3/T4 while Group III was injected with the goitrogen, methimazole, (150 mg/kg BW
per day) for 8 weeks. Chicks (8-9 weeks old) were implanted with catheters in the
brachial wing vein and administered ruthenium-labeled salmon CT. Blood samples
were collected at 30 s, 1, 2, 4, 8, 20 min, and 3 h after injection. Results
showed that concentrations of plasma CT were decreased in T3/T4-injected birds.
There was no significant effect of methimazole on circulating concentrations of
plasma CT. The half-life of CT was significantly increased (P < 0.05) in both
T3/T4-injected (n = 6; 1.34 +/- 0.16 min) and goitrogen-treated birds (n = 2;
5.81 +/- 2.83 min) compared to controls (n = 7; 54 +/- 3 s) The results
demonstrate that changes in concentrations of plasma thyroid hormones can
significantly affect concentrations of plasma CT.
PMID- 10190029
TI - Comparison of the biological activities in venoms from three subspecies of the
South American rattlesnake (Crotalus durissus terrificus, C. durissus cascavella
and C. durissus collilineatus)
AB - The subspecies of the South American rattlesnake, Crotalus durissus are
classified according to their external morphological features and geographical
distribution. We have determined some biological activities of C. durissus
cascavella, C. durissus collilineatus and C. durissus terrificus venoms. C.
durissus terrificus had a significantly higher clotting activity on bovine plasma
and fibrinogen, human fibrinogen and rabbit plasma. C. durissus cascavella
presented a statistically higher phospholipase A2 (PLA2) activity in regard to C.
durissus collilineatus. Their myotoxic and proteolytic activity, median lethal
doses, or median platelet aggregating doses (on rabbit and human platelets) could
not differentiate the three subspecies examined. However, the electrophoretic
profile and the dose-response curve for edematogenic activity for C.d. cascavella
venom were different from the others. With regard to the inorganic element
content of the venoms, higher levels of Br, Cl and Mg, and a lower level of Zn,
were found in C.d. cascavella venom. Crotamine-like activity could not be
detected in C.d. cascavella venom. Furthermore, equine antivenom specific for C.
durissus terrificus venom cross-reacted equally with the antigens of the three
venom pools by ELISA and Western blotting. These results indicate that the venoms
from the three studied subspecies of C. durissus were very similar, except for
minor differences in paw edema-inducing activity, electrophoretic profile,
phospholipase A2 activity, crotamine-like activity and inorganic element contents
of C.d. cascavella venom.
PMID- 10190030
TI - Induction of two major isoforms of metallothionein in crucian carp (Carassius
cuvieri) by air-pumping stress, dexamethasone, and metals.
AB - The induction of metallothionein (MT) by physical and chemical stress was
assessed using the fresh-water fish, crucian carp (Carassius cuvieri Temminck et
Schlegel). The fish exposed to violent air-pumping stress for 6 days revealed
time-dependent induction of MT-like metal-binding proteins in both their livers
and kidneys. Their hepatic contents after exposure to stress were elevated to
twice the basal level with 24 h, resulting in more than a 3-fold increase at 144
h, whereas their renal contents gradually increased after 24 h and reached the
same level as that in the liver around 96 h. Two major inducible proteins were
purified from livers of fish exposed to stress and were shown to be MT based upon
their chromatographic behavior, UV absorption spectra and their molecular
weights. Consequently, they were termed ccMT-1 and ccMT-2, according to their
elution sequence upon anion-exchange chromatography. Both proteins mainly bound
zinc in their endogenous forms and showed different immunogenicity to rat and
rabbit MTs. Dexamethasone, a potent inducer for MT synthesis in mammals, induced
the production of both isoforms in crucian carp, whereas cadmium and zinc ions
prominently induced the synthesis of ccMT-2. These results indicate that crucian
carp have the ability to produce MTs in response to various kinds of
environmental stress and that violent air-pumping stress in crucian carp may
induce MT synthesis, in part, via the release of endogenous factor(s), such as
glucocorticoids.
PMID- 10190031
TI - Effects of beauverolide L and cyclosporin A on humoral and cellular immune
response of the greater wax moth, Galleria mellonella.
AB - The effects of beauverolide L and cyclosporin A, cyclic peptidic metabolites,
produced by several genera of entomopathogenic fungi on immune responses of last
instar larvae of the greater wax moth Galleria mellonella have been examined.
Intrahemocoelic injection of either metabolite-coated silica particles or
dissolved metabolites in a concentrations ranging between 10 and 30 micrograms
per larvae caused no mortality but activated humoral responses in G. mellonella
larvae. The challenge induced a significant release of lysozyme and cecropin-like
activity into the hemolymph, suggesting stimulatory activity on humoral immune
responses. Injected metabolite-coated particles were rapidly surrounded by
hemocytes which subsequently accomplished formation of melanized nodules, which
increased in size and number compared with controls. In vitro assays with
dissolved metabolites indicated no adverse effects of beauverolide L or
cyclosporin A on attachment or spreading of isolated plasmatocytes but dose
dependent inhibition of their phagocytic activity. Isolated plasmatocytes
incubated with cyclosporin A or beauverolide L exhibited cytoskeleton alterations
that differed from those observed in plasmatocytes from infected G. mellonella
larvae or reported from other fungal secondary metabolites. The experiments
provided further data to elucidate the role of fungal secondary metabolites in
development of mycoses in insects.
PMID- 10190032
TI - Inhibition of membrane transport ATPases by halenaquinol, a natural cardioactive
pentacyclic hydroquinone from the sponge Petrosia seriata.
AB - Halenaquinol, a natural cardioactive pentacyclic hydroquinone from the sponge
Petrosia seriata, was found to be a powerful inhibitor of the rat brainstem and
of the rat brain cortex Na+, K(+)-ATPases and the rabbit muscle sarcoplasmic
reticulum Ca(2+)-ATPase with I50 values of 7.0 x 10(-7), 1.3 x 10(-6) and 2.5 x
10(-6) M, respectively. Halenaquinol also inhibited K(+)-phosphatase activity of
the rat brain cortex Na+, K(+)-ATPase with an I50 value of 3 x 10(-6) M. Ouabain
insensitive Mg(2+)-ATPase activity of the microsomal fraction of the rat brain
cortex was weakly inhibited by halenaquinol. Inhibition was irreversible, dose-
and time-dependent. Naphthohydroquinone fragment in structures of halenaquinol,
related natural and model compounds was very important for an inhibiting effect.
PMID- 10190033
TI - Two different modes of inhibition of the rat brain Na+, K(+)-ATPase by triterpene
glycosides, psolusosides A and B from the holothurian Psolus fabricii.
AB - Effects of two triterpene glycosides, isolated from the holothurian Psolus
fabricii, on rat brain Na+, K(+)-ATPase (Na, K-pump; EC 3.6.1.3) were
investigated. Psolusosides A and B (PsA and PsB) inhibited rat brain Na+, K(+)
ATPase with I50 values of 1 x 10(-4) M and 3 x 10(-4) M, respectively. PsA
significantly stimulated [3H]ATP binding to Na+, K(+)-ATPase, weakly increased
[3H]ouabain binding to the enzyme, and inhibited K(+)-phosphatase activity to a
smaller degree than the total reaction of ATP hydrolysis. In contrast, PsB
decreased [3H]ATP binding to Na+, K(+)-ATPase, and had no effect on [3H]ouabain
binding to the enzyme. K(+)-Phosphatase activity was inhibited by PsB in parallel
with Na+, K(+)-ATPase activity. The fluorescence intensity of tryptophanyl
residues of Na+, K(+)-ATPase was increased by PsA and decreased by PsB in a dose
dependent manner. The excimer formation of pyrene, a hydrophobic fluorescent
probe, was decreased by PsA only. The different characteristics of inhibition
mode for these substances were explained by peculiarities of their chemical
structures and distinctive affinity to membrane cholesterol.
PMID- 10190034
TI - Differential resistance to calcium-induced bilirubin-dependent hemolysis in
mammalian erythrocytes.
AB - Washed erythrocytes from human, buffalo, sheep and goat preincubated with
different concentrations of calcium chloride (16.7-1830 microM) showed
significantly different rates of hemolysis (up to 62%) after addition of
bilirubin (72 microM). Goat erythrocytes displayed marked resistance to hemolysis
with only 11% hemolysis observed at the highest calcium concentration. Similar
trend in hemolysis was also observed when the concentration of CaCl2 was fixed
(330 microM) and bilirubin concentration varied (0-72 microM). (Ca(2+)-Mg(2+)
ATPase levels were found significantly lower in goat and sheep erythrocyte
membranes compared to human and buffalo erythrocyte membranes. This was
correlated well with the observed hemolysis in various mammalian erythrocytes.
PMID- 10190035
TI - Effects of exposure to diethyl phthalate, 4-(tert)-octylphenol, and 2,4,5
trichlorobiphenyl on activity of chitobiase in the epidermis and hepatopancreas
of the fiddler crab, Uca pugilator.
AB - Seven-day exposure of fiddler crabs, Uca pugilator, to diethyl phthalate at 50.0
mg l-1 significantly inhibited the activity of chitobiase (also known as N-acetyl
beta-glucosaminidase) in the epidermis and hepatopancreas. Epidermal chitobiase
activity of crabs exposed to 10.0 mg l-1 4-(tert)-octylphenol for 7 days
significantly decreased. PCB29 at 0.5 and 2.0 mg l-1 significantly inhibited
chitobiase activity in the epidermis and hepatopancreas of crabs exposed for 3
days. The inhibitory effects rendered by diethyl phthalate and PCB29 can at least
partly account for the delayed molting they cause because chitobiase is needed to
break down the old exoskeleton of crustaceans prior to ecdysis. Since
chitinolytic enzymes are apparently the products of ecdysteroid regulated genes
in arthropods, the decline in chitobiase activity after exposure to diethyl
phthalate, 4-(tert)-octylphenol, and PCB29 along with the delayed molting they
cause strongly suggests that these xenobiotics disturb the Y-organ-ecdysteroid
receptor axis. Such disturbance may involve an interaction between ecdysteroid
receptors and steroid mimics where the steroid mimics act as antagonists of
endogenous steroid molting hormones, and/or arise from the interference with
synthesis and excretion of ecdysteroids by these compounds.
PMID- 10190036
TI - Inhibitory effects of cadmium on carbonic anhydrase activity and ionic regulation
of the estuarine crab Chasmagnathus granulata (Decapoda, Grapsidae).
AB - This work was aimed at evaluating the gill carbonic anhydrase (CA) activity of
the estuarine crab Chasmagnathus granulata exposed in vivo to cadmium, at
different salinities. The in vivo effect of the specific inhibitor acetazolamide
(AZ) was also assayed. Besides, the inhibition of CA activity by different heavy
metals (cadmium, copper, zinc) and AZ were evaluated under in vitro conditions.
For the in vivo assays, adult males were acclimated to salinities of 2.5 or
30/1000. The corresponding 96-h LC50 of cadmium was 2.69 mg l-1 at 2.5/1000, and
> 50 mg l-1 at 30/1000. Cadmium only caused a significant lower CA activity than
control at 2.5/1000. EC50 for CA inhibition was estimated to be 1.59 mg l-1 at
2.5/1000. Statistical differences in Na+ hemolymphatic levels (P < 0.05) were
only detected at 2.5/1000, between 0 and 1.25 mg l-1 of cadmium, but no
statistical differences were observed for Cl- levels at any assayed salinity. As
CA inhibition registered at 2.5/1000 was followed by only changes in Na+
concentration, it is likely that cadmium exposure could differentially affect
ions permeability, among others factors. The concentrations that inhibited in
vitro 50% of enzymatic activity (IC50) were 2.15 x 10(-5), 1.62 x 10(-5), 3.75 x
10(-6) and 4.4 x 10(-10) M for cadmium, copper, zinc and AZ, respectively. The
comparison with IC50 values of other aquatic species, indicates a higher CA
sensitivity for C. granulata to pollutants.
PMID- 10190037
TI - Uptake of arsenic-betaines by the mussel Mytilus edulis.
AB - Mussels (Mytilus edulis) were exposed to trimethyl(carboxymethyl)arsonium bromide
(arsenobetaine, C-1 betaine), trimethyl(2-carboxyethyl)arsonium bromide (C-2
betaine), or trimethyl(3-carboxypropyl)arsonium bromide (C-3 betaine). Arsenic
was accumulated by the mussels in all cases but the efficiency of uptake
decreased with the number of methylene units in the carboxyalkyl group.
Arsenobetaine (C-1 betaine) was the most readily accumulated, followed by the C-2
betaine (70% as efficient as arsenobetaine) and the C-3 betaine (approximately
7%). Chromatographic analysis (HPLC-ICPMS) of extracts of the mussels
demonstrated that the arsenic compounds were accumulated unchanged. A 46-day
depuration period which followed exposure did not significantly reduce the
arsenic concentration in any of the three groups. Comparison with previous data
on accumulation of arsenic compounds by M. edulis indicates that uptake may be
influenced by the presence of a quaternary arsonium group and the zwitterionic
nature of the arsenic-betaines.
PMID- 10190038
TI - Catechol conjugation with hemolymph proteins and their incorporation into the
cuticle of the American cockroach, Periplaneta americana.
AB - Newly ecdysed American cockroaches, Periplaneta americana (sixth to last instar)
were injected with radioactive dopamine (DA) and hemolymph was collected at 10-60
min post-ecdysis. Size-exclusion chromatography established the presence of at
least three proteins that serve as catecholamine carriers. Reinjection of the
smaller radiolabeled phenol-bound proteins into newly ecdysed animals results in
in vivo aggregation, with the radiolabel bound to large MW proteins (30- > 200
kDa). In addition, the reinjection of radiolabeled protein of any size resulted
in the incorporation of the label into the newly sclerotized cuticle. Hemolymph
proteins were synthesized in vivo using [14C]leucine and subsequently double
labeled in vivo with [3H]dopamine. After sclerotization (7 h post-ecdysis) the
cuticle was extirpated, hydrolyzed and counted. An identical ratio of 14C to 3H
was found in cuticle extracts as in the double-labeled hemolymph proteins,
suggesting that the phenol-bound protein was incorporated in the cuticle
unchanged. It appears that the catechol bound to the proteins exists as a beta
glucoside.
PMID- 10190039
TI - Survival in air of Mytilus trossulus following long-term exposure to spilled
Exxon Valdez crude oil in Prince William Sound.
AB - Mussels, Mytilus trossulus, were sampled in 1996 from beaches in Prince William
Sound (PWS) which contained residual oil resulting from the Exxon Valdez oil
spill of March 1989, and from one beach which had been lightly oiled in 1989, but
contained no residual oil in 1996. The latter mussels served as un-oiled
references. Mussels were also collected from Tee Harbor, Southeast Alaska, to be
used as an additional reference group. Where the size of the individuals in the
resident population would permit, two size groups were sampled, 32-35 and 18-20
mm in length. Polynuclear aromatic hydrocarbon (PAH) concentrations in mussel
tissue, and air survival time were determined for each group of mussels. Total
PAH concentrations were significantly greater in tissue of mussels from oiled
beds (0.6-2.0 micrograms g-1) than from references (0.01-0.12 microgram g-1) (P <
0.01). Oil-exposed mussels had significantly lower LT50 values (P < 0.05) for air
survival than reference groups. Tolerance of small mussels to air exposure was
significantly greater (P < 0.01) than large mussels in both the unoiled reference
and oil exposed groups.
PMID- 10190040
TI - Lack of physiological responses to hydrocarbon accumulation by Mytilus trossulus
after 3-4 years chronic exposure to spilled Exxon Valdez crude oil in Prince
William Sound.
AB - Mussels, Mytilus trossulus, were sampled in 1992 and 1993 from beaches in Prince
William Sound that had been oiled by the Exxon Valdez spill of March, 1989. At
some of the oiled beaches, mussels were collected from beds overlying oiled
sediments, and from bedrock adjacent to these beds. Mussels were also collected
from beaches within the Sound that had not been impacted by the spill.
Polynuclear aromatic hydrocarbon (PAH) concentrations in mussel tissue,
physiological responses (byssal thread production, condition index, clearance
rate, and glycogen content), were determined for each group of mussels. Total PAH
concentrations in mussel tissue ranged from 0 to 6 micrograms g-1, and were
significantly greater in mussels from oiled beds than those from reference beds.
No significant differences were noted in byssal thread production, condition
index, clearance rate, or glycogen content between oiled sample sites and
reference sites. The lack of physiological response was surprising because
mussels in this study were chronically exposed to PAH for 3-4 years, and none of
the physiological responses measured appeared to be affected by that exposure.
The lack of a physiological response suggests that chronically exposed mussels
may develop a physiological tolerance to PAH, but we recognize that these
measures may not have been sensitive enough to discriminate response from
background noise.
PMID- 10190041
TI - NANC relaxation of the circular smooth muscle of the oesophagus of the Agama
lizard involves the L-arginine-nitric oxide synthase pathway.
AB - On carbachol (CCh; 10-30 microM) pre-contracted circular muscle strips of the
Agama lizard oesophagus, electrical field stimulation evoked frequency-dependent
relaxations in the presence of guanethidine (1 microM) and indomethacin (1
microM). These non-adrenergic inhibitory responses were concentration-dependently
inhibited by the nitric oxide synthase (NOS) inhibitor N omega-nitro-L-arginine
methyl ester (L-NAME) within a concentration range of 30-300 microM but not D
NAME (up to 300 microM), although a component remained at 4-16 Hz even with 300
microM L-NAME. The inhibition by L-NAME (300 microM) was completely prevented
when L-arginine (L-Arg; 15 mM) but not D-Arg (up to 15 mM) was applied
simultaneously with L-NAME (300 microM). Increasing the L-NAME concentration to 1
mM had no additional inhibitory effect. Sodium nitroprusside (SNP) concentration
dependently relaxed pre-contracted oesophageal strips, L-NAME (up to 300 microM)
had no effect. Neither adenosine 5'-triphosphate (up to 0.1 mM) nor vasoactive
intestinal polypeptide (up to 0.1 microM) caused the pre-contracted oesophagus to
relax. This study has shown that the NANC inhibitory response of the Agama lizard
oesophagus circular muscle largely involves the L-Arg-NOS pathway as seen by the
effect of L-NAME, L-Arg and SNP. The identity of the L-NAME-resistant
component(s) and the lack of effect of tetrodotoxin (up to 3 microM) and omega
conotoxin GVIA (up to 0.1 microM) in relation to the nature of the inhibitory
response are discussed.
PMID- 10190042
TI - The effect of ACTH on the GnRH-induced release of LH and testosterone in male
white-tailed deer.
AB - In order to investigate the possible link between stress and the impairment of
the reproductive system, 12 yearling white-tailed bucks, born to mothers captured
wild in southern Texas, were immobilized every 6 weeks over the period of 1 year.
In half of experiments deer were injected i.m. with 20 i.u. of ACTH; in the
second half, we used saline only. Simultaneously, in each experiment we also
injected all deer i.m. with 100 micrograms of GnRH. Three blood samples were
taken before and seven after treatment and plasma levels of cortisol, LH and
testosterone (T) were later measured by RIA. Half of our yearlings were born to
mothers which were fed high-protein-high-energy (HP-HE) diet during their
pregnancy; the other half ws fed high-protein-low-energy diet (HP-LE). ACTH
increased cortisol levels in both nutritional regimes. Cortisol levels in
controls decreased with time but a more pronounced reduction was observed in HP
HE bucks as compared to HP-LE deer. GnRH significantly increased LH and T levels.
However, only in summer, LH levels were higher in HP-LE fed deer than those fed
HP-HE; in other seasons they were equal. Conversely, only in winter T levels were
elevated in HP-HE fed deer as compared with HP-LE deer. We concluded that the
pronounced suppression of reproductive hormones by ACTH or cortisol reported
previously in domestic ungulates does not occur in white-tailed deer yearlings.
Conversely, the low level of energy provided in food to mothers during their
pregnancies significantly reduced peak levels of testosterone in their male
offspring. This study further proved that white-tailed deer is a highly adaptable
cervid species resistant to environmental stress.
PMID- 10190043
TI - Inhibition kinetics of human serum butyrylcholinesterase by Cd2+, Zn2+ and Al3+:
comparison of the effects of metal ions on cholinesterases.
AB - Butyrylcholinesterase (BChE, EC 3.1.1.8) has been purified about 6600-fold from
human serum with a procedure including ammonium sulfate fractionation (55-70%)
with acid step at pH 4.5 and procainamide-Sepharose 4B affinity chromatography.
The purified enzyme exhibited negative cooperativity with respect to
butyrylthiocholine (BTCh) binding at pH 7.5. Ks was found to be 0.128 +/- 0.012
mM. Inhibition kinetics of the enzyme by Cd2+, Zn2+ and Al3+ were studied in
detail. The 1/v vs 1/[BTCh] plots in the absence (control plot) and in the
presence of different concentrations of cations intersected above 1/[BTCh]-axis.
The data were analyzed by means of a nonlinear curve fitting program. The results
demonstrated that all of the three cations are the linear mixed-type inhibitors
of BChE. Ca2+ and Mg2+ had no effect on the enzyme activity in the experimental
conditions. But when the enzyme was inhibited by 0.5 mM Cd2+ or Zn2+, Ca2+ and
Mg2+ partially reactivated the inhibited allosteric form of BChE. Results were
compared with data obtained from brain BChE purified from sheep.
PMID- 10190044
TI - Responsiveness of the hypothalamo-pituitary-interrenal axis in an amphibian (Bufo
terrestris) exposed to coal combustion wastes.
AB - To assess the responsiveness of the interrenal axis to stress, we injected toads
exposed to coal combustion wastes and toads from an unpolluted reference site
with adrenocorticotropic hormone (ACTH), as well as the vehicle alone (saline).
Initial circulating levels of corticosterone in toads captured at the polluted
area were significantly higher than levels in toads from the reference site.
Corticosterone levels in toads from the polluted site remained high even after 2
weeks of laboratory acclimation and injection with saline. The results may
suggest disruption of hepatic enzymes responsible for the metabolic clearance of
steroid hormones. Injection of toads from the polluted site with ACTH had no
effect on plasma corticosterone levels, whereas a similar treatment of toads from
the reference site stimulated a marked increase in corticosterone. Our study
provides evidence that toads exposed to coal combustion wastes may be less
efficient at responding to additional environmental stressors.
PMID- 10190046
TI - Noncompetitive mixed-type inhibition of rainbow trout CYP1A catalytic activity by
clotrimazole.
AB - Over the past two decades a number of antifungal imidazole derivatives have been
approved for use in agricultural. The purpose of this study was to characterize
the interaction of a model antifungal imidazole compound with a cytochrome P450
isozyme in a species of fish. Clotrimazole inhibited rainbow trout (Oncorhyncus
mykiss) hepatic CYP1A-catalyzed ethoxyresorufin O-deethylase (EROD) activity in
vivo and in vitro. Although clotrimazole inhibited EROD activity in vivo, it did
not effect CYP1A mRNA levels. Addition of clotrimazole to microsomes produced a
type II binding spectrum and clotrimazole was determined to be a noncompetitive
mixed-type inhibitor of EROD activity with an IC50 of 190 nM. Since antifungal
imidazole compounds may be co-applied with other pesticides, inhibition of
cytochrome P450 activity by antifungal imidazole compounds may lead to unexpected
toxicological interactions.
PMID- 10190045
TI - Human, rat and crocodile liver microsomal monooxygenase activities measured using
diazepam and nifedipine: effects of CYP3A inhibitors and relationship to
immunochemically detected CYP3A apoprotein.
AB - Nifedipine oxidase and diazepam C3-hydroxylase were tested as activities for
selectively measuring CYP3A enzymes using liver microsomes from male and female
human organ donors, male and female Wistar rats and male and female estuarine
crocodiles. The association between CYP3A enzymes and these monooxygenations was
confirmed for the human samples. Male rat samples had lower specific contents of
CYP3A apoprotein than the human samples but had equivalent (nifedipine) or higher
(diazepam) monooxygenase specific activities. CYP3A apoprotein was undetectable
in female rat samples which had very low activities towards both substrates.
Enzyme inhibition studies showed that diazepam C3-hydroxylase of male rat liver
was attributable to CYP3A but corresponding results for female rats suggested a
contribution from non-CYP3A enzyme. Western blotting with immunochemical
detection using anti-CYP3A4 IgG suggested the presence of putative CYP3A
apoprotein in male and female crocodile liver samples and inhibition studies with
diazepam as substrate suggested the presence of CYP3A subfamily monooxygenase
activity in these enzyme preparations. Results for nifedipine oxidase with male
and female rat liver and male crocodile liver suggested major contributions to
catalysis from non-CYP3A enzymes. Inhibition studies suggested that a higher
proportion of nifedipine oxidase in female crocodile liver may be attributable to
the putative CYP3A enzyme(s) than in male crocodile liver. These results show the
need for care in the assessment of CYP3A activity of fractionated tissues when
using these substrates in cross-species studies and where gender is a variable.
PMID- 10190047
TI - A phenolic antioxidant from the freshwater orchid, Habenaria repens.
AB - Recently, an unusual compound named habenariol was isolated from the freshwater
orchid, Habenaria repens. Its phenolic structure suggested that habenariol should
have substantial antioxidant activity. This possibility was investigated by
evaluating the capacity of habenariol to inhibit copper-induced lipid
peroxidation of human low density lipoprotein (LDL), a popular experimental
model. LDL was incubated with 5 microM cupric chloride in the presence and
absence of habenariol or a positive control, viz., alpha-tocopherol. Both kinetic
and end-point spectrophotometric assays were used to determine extent of lipid
peroxidation of LDL. In the kinetic assay, the time elapsing before the onset of
rapid formation of conjugated lipid hydroperoxides in LDL (marked by a sharp
increase in UV absorbance) was prolonged by habenariol, indicative of an
antioxidant effect. In the end-point assay, direct colorimetric measurement
confirmed habenariol's ability to inhibit formation of lipid hydroperoxides.
However, in both assays, habenariol was less potent than alpha-tocopherol in
inhibiting lipid peroxidation of LDL.
PMID- 10190048
TI - Effect of C2 ceramide on the inositol phospholipid metabolism (uptake of 32P, 3H
serine and 3H-palmitic acid) and apoptosis-related morphological changes in
Tetrahymena.
AB - Sphingomyelin metabolites have significant role in the regulation of many life
processes of mammalian cells. In the present experiments the influence of
phospholipid turnover and apoptosis related morphologic signs by one of this
metabolite, C2 ceramide was studied, and compared to the control, untreated
cells, in the unicellular Tetrahymena. The incorporation of phospholipid head
group components (serine, phosphorus) show a clear time-dependence; while the
incorporation of fatty acid component (palmitic acid) is very fast: no
significant alterations were found between 5- and 60-min incubations. C2 ceramide
treatment didn't alter 3H-palmitic acid incorporation into phospholipids, however
3H-serine incorporation was mainly inhibited. The amount of total incorporated
32P was also decreased, on the other hand the lover concentration C2 ceramide (10
microM) elevated the synthesis of inositol phospholipids. The higher
concentration of C2 ceramide (50 microM) had inhibitory effect on the synthesis
of each phospholipids examined. This means that in the presence of the C2
ceramide the synthesis, recovery and turnover of phospholipids, participating in
signal transduction, are altered. However these observations were based the
uptake of labeled phospholipid precursors, which gives information on the
dynamics of the process, without using lipid mass measurements. C2 ceramide also
caused the rounding off the cells, DNA degradation and nuclear condensation.
These latter observations point to morphological signs of apoptosis. The results
call attention to the role of sphingomyelin metabolites on signalization of
unicellulars, to the cross-talk between the inositol phospholipids and
sphingomyelin metabolites, and the role of these molecules in the apoptotic
processes at a low evolutionary level.
PMID- 10190049
TI - A novel method to evaluate the relative tannin-binding capacities of salivary
proteins.
AB - Many herbivore species have a diet containing high proportions of polyphenolics,
principally lignins and tannins; the latter reduce the conversion of ingested
nutrients into biomass and exert systemic toxicity at high levels of intake. It
has been proposed that tannin-binding proteins in the saliva might be responsible
for minimizing these tannin-related effects by forming soluble protein-tannin
complexes. We have developed a method that permits evaluation of the relative
tannin-binding properties of salivary proteins at a pH of 8.0-8.5. It is aimed at
facilitating both the identification of tannin-binding proteins and the
investigation of their relative tannin binding. The principle of the assay is the
inhibition of trypsin by tannins and the subsequent reversal of that inhibition
when other tannin-binding proteins are added (indirect assay). The method is
rapid; large sample numbers may be processed by virtue of its microtiterplate
format.
PMID- 10190050
TI - Cytochemical localization of vanadium(III) in blood cells of ascidian Phallusia
mammillata Cuvier, and its relevance to hematic cell lineage determination.
AB - When the blood cells of ascidians Phallusia mammillata are stained with the
ligand 2,2'-bipyridine, those cells which contain vanadium(III), in an easily
sequestered form, take up the stain producing in situ, a purple complex. This
material extracted displays spectral characteristics consistent with the
formation of an oxo-bridge vanadium(III) bipyridine dimer. The staining is
localized in the signet ring cell, a bivacuolated cell, a cell type with numerous
darkly staining compartments, and also by the vacuolated amoebocyte. The possible
ramifications of these observation are discussed in relation to the delineation
of the signet ring cell lineage.
PMID- 10190051
TI - Antigen-induced elevation of immunoreactive endothelin-1 (ET-1) levels in
ovalbumin-sensitized guinea pig airway tissue.
AB - Changes in the immunoreactive ET-1 levels during the anaphylactic reaction of
airway tissue from ovalbumin-sensitized guinea pigs were investigated. ET-1
immunoreactivity (ET-IR) was detected in the epithelial and smooth muscle layers
of tracheal sections from normal guinea pigs and it was enhanced slightly by
phosphoramidon (1 microM) treatment. The ET-IR level of the epithelial layer of
ovalbumin-treated tissue from actively sensitized animals was slightly higher
than that from normal animals, but it was enhanced markedly by phosphoramidon (1
microM) treatment. Furthermore, the mean ET-IR level of homogenates of antigen
treated tracheal tissues from sensitized guinea pigs (22.8 +/- 1.55 fmol mg-1
protein, n = 5) was significantly higher than the corresponding normal level
(12.3 +/- 1.21 fmol mg-1 protein, n = 5). These results suggest that increased
epithelial airway ET-1 levels contribute to the anaphylactic reaction of guinea
pig airways.
PMID- 10190052
TI - Antimitogenic effect of Larrea divaricata Cav.: participation in arachidonate
metabolism.
AB - Aqueous extracts of the leaves of Larrea divaricata Cav. exert antimitogenic
effects on tumor cells (BW 5147 murine immature T-lymphoma) and normal,
stimulated lymphocytes. The effective concentration was four times smaller in the
case of tumor cells than in the case of normal, stimulated lymphocytes. Inhibitor
studies of arachidonate pathway suggest that the proliferative effect of the
extract is due to the activation of lipoxygenase metabolism, while the inhibitory
action could be a direct effect.
PMID- 10190053
TI - Effect of heavy metals (Cu, Cd and Pb) on aspartate and alanine aminotransferase
in Ruditapes philippinarum (Mollusca: Bivalvia).
AB - The accumulation of cadmium, copper and lead and their effects on aspartate and
alanine aminotransferases in digestive gland, gills, foot and soft body in the
clam Ruditapes philippinarum were examined. The animals were exposed to different
concentrations: Cd (200-600 micrograms.l-1), Pb (350-700 micrograms.l-1) and Cu
(10-20 micrograms.l-1) for 7 days. The highest concentrations were found in
digestive gland for cadmium and copper, and in gills for lead, and the lowest
values were observed in the foot. Aspartate aminotransferase activity (AST), in
general, was not inhibited by cadmium, lead or copper during the exposure. Only
in clams exposed to cadmium (600 micrograms.l-1, 7 days) and copper (20
micrograms.l-1, 5 days) were observed significant differences (P < 0.05) in foot
and gills, respectively, with respect to control. In the case of alanine
aminotransferase activity (ALT), significant differences were observed for
cadmium and lead in treated animals with respect to control. With regard to
copper, a decrease in ALT was observed in gills and foot exposed to 20
micrograms.l-1. A significant correlation (P < 0.05) was observed between ALT and
metal accumulation for cadmium, copper and lead in gills. In the case of soft
body, only cadmium and lead showed a significant correlation. In summary, R.
philippinarum can be considered a bioindicator species for cadmium and lead
accumulation and ALT could be useful as biomarker of sublethal stress for these
metals in soft tissues and gills can be considered an adequate target tissue for
copper.
PMID- 10190054
TI - Antioxidant system of Black Sea animals in early development.
AB - Activities of lipoxygenase, catalase, superoxide dismutase, peroxidase,
glutathione reductase and content of low molecular weight antioxidants were
determined in eggs and larvae of some molluscs, crustaceans, elasmobranchs and
teleost fish of the Black Sea. The enzyme activities and concentrations of low
molecular weight antioxidants showed marked interspecies differences, depending
on specific developmental peculiarities. During marine animal embryogenesis the
activities of lipoxygenase and most of the examined antioxidant enzymes tended to
increase in eggs and especially in hatching larvae, while the contents of low
molecular weight antioxidants were decreased. High correlations between
antioxidant enzyme activities (0.52 < r < 0.96), content of low molecular weight
antioxidants (0.58 < r < 0.99) and developmental stages of examined marine
animals were established.
PMID- 10190055
TI - Identification of in vitro cytochrome P450 modulators to detect induction by
prototype inducers in the mallard duckling (Anas platyrhynchos).
AB - Seven modulators of mammalian monooxygenase activity were screened for their
ability to selectively stimulate or inhibit in vitro monooxygenase activities of
hepatic microsomes from mallard ducklings treated with phenobarbital, beta
naphthoflavone, 3,3',4,4',5-pentachlorobiphenyl or vehicle. Microsomes were
assayed fluorometrically for four monooxygenases: benzyloxy-, ethoxy-, methoxy-,
and pentoxyresorufin-O-dealkylase, in combination with each of the seven
modulators. Four combinations: alpha-naphthoflavone and 2-methylbenzimidazole
with benzyloxyresorufin, and Proadifen with methoxy- and ethoxyresorufin,
respectively, were evaluated further. beta-Naphthoflavone-treated groups were
clearly distinguished from the corn oil vehicle control group by all of the
assays and by the effects of the modulators in three of the four assay/modulator
combinations. Enzyme activities of the phenobarbital and saline groups were
statistically similar (P > or = 0.05) when assayed without modulator added, but
each assay/modulator combination distinguished between these groups. The PCB
treated group was distinguished from the corn oil vehicle control group only for
BROD activity, with or without the presence of modulator. Graphing of per cent
modulation of BROD activity versus initial BROD activity provided the clearest
distinction between all of the study groups. Identification of these selective in
vitro modulators may improve detection and measurement of low level cytochrome
P450 induction in avian species. Also, both the monooxygenase activities induced
and the impacts of the modulators indicated differences between mammalian and
avian cytochromes P450.
PMID- 10190056
TI - Insecticidal properties of 3-aminopropyl(methyl)phosphinic acid and its effect on
K(+)-evoked release of acetylcholine from cockroach synaptosomes.
AB - 3-Aminopropyl(methyl)phosphinic acid (APMP), a potent agonist of mammalian GABAB
receptors, caused prostration in houseflies (Musca domestica L.) on injection
into their thoraces, with an ED50 value of 0.42 microgram/fly. The 48-h LD50
values of APMP were estimated to be 0.45 and 5.6 micrograms/fly in the presence
and absence of piperonyl butoxide, a mixed-function oxidase inhibitor,
respectively. Analogues of APMP, bearing a longer or shorter side chain by a CH2
unit, or a phenyl group in the place of the methyl group, were without effects.
In perfusion assays with synaptosomes prepared from the thoracic/abdominal nerve
cords of cockroaches (Periplaneta americana L.), 1 mM APMP reduced K(+)-evoked
acetylcholine release to 10.4% of the control. These findings indicate that the-
physiologically important site of action of APMP, which might be implicated in
neurotransmitter release, is present in insect neurons.
PMID- 10190058
TI - Smoking: an ugly habit.
PMID- 10190057
TI - Cloning and characterization of metallothionein cDNAs in the mussel Mytilus
edulis L. digestive gland.
AB - Metallothioneins are small metal-binding proteins found in all species of animals
and are transcriptionally-induced by heavy metal ions, oxidative stresses, and
inflammation. In the blue sea mussel, Mytilus edulis, several apparent subtypes
of each isoform have been purified and biochemically sequenced. To determine
whether the high number of metallothionein forms present in M. edulis were
specific to the digestive gland, and to understand how these proteins evolved, we
cloned five variants of metallothionein from M. edulis. MT10 and MT20 isoform
fragments were amplified by PCR, and used as radiolabelled probes to screen
digestive gland cDNA libraries. The MT10 transcripts were 321-353 nucleotides
long and the MT20 transcripts, 513-555 nucleotides. Previously identified primary
structures of MT10 subtypes were confirmed and, in addition, a novel subtype was
identified. Expression of MT10 and MT20 isoforms shown by clonal representation
and Northern blot analysis indicated that the MT10 message was more prevalent
than the MT20 message. Only the MT20 II transcript could be identified among the
MT20 clones. The high degree of untranslated region similarity between each
isoform indicates that these additional forms are recent gene duplication events
in the Mytilus lineage. Exposure of 0.4 mg l-1 of cadmium to the mussels resulted
in a marked increase in both mRNAs suggesting that the MT20 isoform represents a
primarily inducible metallothionein not highly expressed under basal conditions.
PMID- 10190059
TI - Sports-related cutaneous reactions: Part I. Dermatoses due to physical agents.
PMID- 10190060
TI - Botanical briefs: Peruvian lily--Alstroemeria (L.) spp.
PMID- 10190061
TI - Waardenburg's syndrome with facial palsy and lingua plicata: is that a new type
of disease?
PMID- 10190062
TI - Tretinoin-induced sticky skin: a case report and review of the literature.
AB - Sticky skin has been reported relatively infrequently in the literature in
association with etretinate and doxorubicin/ketoconazole administration. It has a
poorly understood pathogenesis, and the associated histologic changes have not
been described. We report a case of a patient who experienced sticky skin in
areas treated with tretinoin. These reverted to normal after cessation of
treatment. In comparison to a biopsy taken while the skin was not sticky, the
histologic findings included a thickened, compact stratum corneum and granulosum.
The basal epithelial cells showed proliferation with slight crowding and a tall,
columnar shape. To our knowledge, this is the first report of sticky skin
occurring in response to topical retinoid application. We suggest that the
histologic changes observed could represent a modified keratin maturation
profile.
PMID- 10190063
TI - Multinucleate-cell angiohistiocytoma occurring in a patient with mycosis
fungoides.
AB - Multinucleate-cell angiohistiocytoma (MCAH) is a benign vascular proliferation of
unknown etiology. Clinically, MCAH presents as grouped, erythematous, or
violaceous papules on the extremities in older women. These lesions often
resemble Kaposi's sarcoma. Histologic examination reveals characteristic bizarre
shaped, multinucleate giant cells, some of which contain three to six nuclei
arranged in a ring-like or overlapping pattern, which stain positively for Factor
XIIIa. In addition, there is a proliferation of dermal capillaries and venules
with a mild lymphohistiocytic infiltrate. To our knowledge, this is the first
reported case of MCAH occurring in a patient with mycosis fungoides.
PMID- 10190064
TI - Calciphylaxis: case report and treatment review.
AB - We present the case of a 57-year-old white woman with chronic renal failure as
well as severely painful, firm, indurated plaques on the thighs and lower
extremities. The plaques progressed to involve larger areas with associated local
ulceration and necrosis. Laboratory testing revealed hyperparathyroidism, and
incisional biopsy confirmed calcifying panniculitis.
PMID- 10190065
TI - Allergic contact dermatitis from transdermal clonidine in a patient with mycosis
fungoides.
AB - Although therapy with transdermal clonidine is considered an effective method of
hypertension control, this mode of delivery has been associated with localized
dermal reactions in numerous patients. We present a patient with coexistent
mycosis fungoides and allergic contact dermatitis from transdermal clonidine. The
association of these two dermatologic processes has not been previously reported.
PMID- 10190066
TI - Esophagitis dissecans superficialis associated with pemphigus vulgaris.
AB - The extension of bullous lesions in pemphigus to the esophagus is relatively
uncommon, especially in patients who appear to be in clinical remission. Very
rarely, pemphigus vulgaris may affect the entire esophagus, resulting in complete
sloughing of the mucous membrane. A 20-year-old man with pemphigus vulgaris
presented to the emergency room with acute onset of dysphagia, odynophagia, and
hemoptysis. There were no cutaneous or oral findings of pemphigus on
presentation, since he was being maintained on corticosteroids and azathioprine
with excellent results. During initial evaluation in the emergency room, the
patient was observed to vomit a cast of the mucosal lining of the esophagus. The
morphologic description of such an esophageal cast is termed esophagitis
dissecans superficialis. This is the third case of esophagitis dissecans
superficialis in pemphigus vulgaris recorded in the medical literature.
PMID- 10190067
TI - Subcutaneous nodules caused by Pseudomonas aeruginosa without sepsis.
AB - Pseudomonas aeruginosa infection can cause a wide array of skin manifestations.
While some infections are mild, as are the cases with hot tub folliculitis and
toe web or nail infection, others are a result of sepsis and can be fatal without
prompt treatment. The classic skin finding of P. aeruginosa sepsis is Ecthyma
gangrenosum, but other signs such as papules, petechiae, and hemorrhagic bullae
can also be seen. Suppurative panniculitis can also be caused by P. aeruginosa
sepsis and clinically manifests as solitary or multiple subcutaneous nodules.
Reports in the literature describe these nodules in the setting of clinical
sepsis or with positive blood cultures. We report a case of localized
subcutaneous nodules on the leg caused by P. aeruginosa in a patient without
sepsis or positive blood cultures. The source of the infection was thought to be
from a traumatic inoculation. This raises the possibility that P. aeruginosa can
cause subcutaneous nodules from a localized infection, perhaps via lymphangitic
spread without the manifestations of sepsis.
PMID- 10190068
TI - Metastatic basal cell carcinoma to the lung.
AB - Basal cell carcinoma is a relatively common tumor with an increasing incidence.
Despite this, metastatic disease is an extremely rare event. A review of
metastatic basal cell carcinoma is presented.
PMID- 10190069
TI - Unusual presentation of a salivary pleomorphic adenoma: a case report and review
of the literature.
AB - Although pleomorphic adenomas are the most common neoplasms of salivary gland
origin, our knowledge of the etiology, growth, and recurrence patterns, and
significance of the varying histologic features of these tumors, remains limited.
We present the case of a 66-year-old man with an unusual presentation of a
pleomorphic adenoma, and review the important clinical and pathologic features of
this entity.
PMID- 10190070
TI - Pityriasis amiantacea.
AB - Pityriasis amiantacea is an easily recognizable cutaneous disease that is
characterized by scaling of the scalp and temporary alopecia. The scaling,
described as thick and asbestos-like, binds down tufts of hair. The alopecia may
be temporary or scarring. Despite a well-established clinical description, no
definitive etiology has been uncovered. This disease may represent seborrheic
dermatitis, superficial fungal or pyogenic infections, lichen planus, or
psoriasis. Histologically, the disease is characterized by eczematous features.
We report a case of pityriasis amiantacea in an 11-year-old girl with
simultaneous findings of psoriasis as well as review the literature on the
etiology of this disease.
PMID- 10190071
TI - Acute infection with Trichophyton rubrum associated with flares of atopic
dermatitis.
AB - Trichophyton rubrum has been implicated as a potential trigger in flares of
atopic dermatitis. We describe a patient with atopic dermatitis who presented
with a history of multiple flares and concurrent acute tinea pedis and
onychomycosis. Symptoms of atopic dermatitis and culture-positive acute infection
with T. rubrum resolved during each flare using systemic antifungals. Flares of
atopic dermatitis may be triggered by acute T. rubrum infections. Antifungal
therapy should be considered in these patients.
PMID- 10190072
TI - Lymphocutaneous sporotrichosis: a case report and unconventional source of
infection.
AB - A 32-year-old white man had a 5-month history of a progressively worsening rash
on the dorsal aspect of his left foot. He stated that he engaged in self
tattooing of the left foot prior to the onset of the rash. Further questioning
revealed that he had mowed the lawn wearing only sandals on the same day that he
had tattooed his foot. The rash was diagnosed as lymphocutaneous sporotrichosis
based on clinical appearance, biopsy examination, and fungal culture. Clearing of
the lesions was documented following 4 months of therapy with itraconazole. The
remaining granulomatous lesions were flattened with intralesional corticosteroid
injections.
PMID- 10190073
TI - Nitrofurantoin-associated Sweet's syndrome.
AB - A 53-year-old woman was seen for arthralgias, fever, and a painful rash
developing at the end of a 7-day course of nitrofurantoin for a urinary tract
infection. Her only other medication was naproxen, which was started after the
onset of symptoms. Initial biopsy showed microscopic changes suggestive of a
toxic eruption, but within 3 days the clinical signs and symptoms typical of
Sweet's syndrome evolved. A repeat biopsy showed microscopic features
characteristic of that diagnosis. The patient subsequently cleared with
prednisone therapy. We report this patient as a case consistent with drug-induced
Sweet's syndrome induced by nitrofurantoin.
PMID- 10190074
TI - Tetracycline and niacinamide: treatment alternatives in ocular cicatricial
pemphigoid.
AB - Cicatricial pemphigoid (CP) is one of the subepidermal autoimmune bullous
dermatoses in which pathologic separation occurs between the epidermis and
dermis. Ocular findings characteristic of CP include conjunctival cicatrization,
subepithelial fibrosis, and symblepharon formation, which may progress to
blindness. Ocular CP (OCP) is usually treated with steroids or immunosuppressive
agents, which are problematic in and of themselves within the elderly population,
which is most often afflicted with OCP. We describe the utility and effectiveness
of therapy with tetracycline and niacinamide in elderly patients with OCP.
PMID- 10190075
TI - Disseminated cutaneous protothecosis in an immunocompromised host: a case report
and literature review.
AB - Protothecosis is an infection caused by achloric algae of the genus Prototheca.
These organisms have been isolated from water, sewage, soil, and the slime flux
of trees, and are a known cause of disease in other mammals. Infection in humans
occurs after traumatic inoculation, producing localized olecranon bursal or,
rarely, systemic disease. Only two previous cases of disseminated cutaneous
disease have been reported in patients with defective neutrophil function. We
describe a rare case of widespread cutaneous dissemination occurring after an
arthropod bite in an immunocompromised patient.
PMID- 10190076
TI - Contact hypersensitivity to mercury in amalgam restorations may mimic oral lichen
planus.
AB - Oral lichenoid lesions caused by hypersensitivity to mercury in amalgam fillings
may mimic oral lichen planus on clinical and histologic examination. A positive
patch test reaction to more than one mercurial allergen increases confidence in
the diagnosis and justifies the removal and replacement of all amalgam fillings
with those made of other materials. A complete remission may be expected about 3
months after the last amalgam filling is removed.
PMID- 10190077
TI - Ukrain (NSC-631570) in experimental and clinical studies: a review.
AB - The need to find a safe and highly effective cure for neoplastic disease remains
a major challenge for modern pharmacology. This paper reviews the available
literature on Ukrain (NSC631570), a novel semisynthetic drug obtained from
Chelidonium majus L. alkaloids. Ukrain has been demonstrated to possess
antineoplastic and immunomodulatory properties. Inhibition of the growth of
cancer cell lines in vitro, tumor mass reductions in vivo, and partial and
complete remissions in oncological patients, occur as a result of Ukrain
application. The drug may interfere directly with the metabolism of cancer cells
and it also improves the functioning of the host immune system. Diminished
synthesis of DNA, RNA and proteins, the inhibition of cellular oxygen
consumption, and the induction of programmed cell death in malignant cells have
been described following Ukrain administration. The drug can also modify the
immunological response via an increase in the number of total T-cells and a
normalization of the T-helper/T-suppressor lymphocyte ratio. Ukrain therapy
produces neither toxic consequences nor allergic reactions towards the drug.
Several case reports and clinical trial data indicate that Ukrain may ameliorate
effectively the progress of neoplastic disease and/or induce a total cure.
PMID- 10190078
TI - Comparative evaluation of the complex treatment of rectal cancer patients
(chemotherapy and X-ray therapy, Ukrain monotherapy).
AB - A total of 48 patients suffering from rectum cancer were included in this
randomized study conducted at the Proctology Department of the Donetsk Regional
Anti-Cancer Center. Patients in group I (24 patients) received an intensive
course of high fractional X-ray therapy (cumulative dose up to 25 Gy) with direct
protracted endolymphatic chemotherapy with 5-fluorouracil (5-FU) instilled in 600
mg/m2 each day before operation, up to a cumulative dose of 5 g. The 24 patients
in group II were treated with Ukrain as monotherapy, 10 mg each second day before
operation (up to a cumulative dose of 60 mg) and a total of 40 mg after surgical
intervention. Repeated Ukrain courses (100 mg/per course) were also given 6
months after surgical operation. In each ease preoperative treatment was followed
by routine surgical operation. Prolongation morbi were found to have developed 14
months later in six patients in group I (25.0%), whereas in group II they were
found only in two cases (8.3%). Comparative investigation of objective and
subjective signs, analysis of results of instrument and X-ray data, as well as
dynamic study of the histological structure of rectal tumors, indicate that
Ukrain exerts a more potent malignotoxic and immunomodulating action than other
types of anticancer treatment.
PMID- 10190079
TI - Ukrain therapy of stage T1N0M0 bladder cancer patients.
AB - The aim of the present study was to evaluate the efficacy of Ukrain as a new
treatment modality in 28 patients with stage T1N0M0 bladder cancer. The tumor
dimensions varied from 0.5 x 0.5 cm to 3 x 4 cm. The first group (nine patients)
was treated with a total dose of 100 mg Ukrain, the second group (10 patients)
received 200 mg Ukrain, and the third group (nine patients) was treated with 300
mg Ukrain. In all patients Ukrain was administered i.v. at a dose of 10 mg per
day. In the patients from the second and third group each course of treatment,
consisting of 10 injections, was followed by 14 days of no treatment. Ukrain, at
a total dose from 100-300 mg as neoadjuvant therapy in patients with T1N0M0
bladder cancer, resulted in either complete or partial regression of tumors in
60.7 +/- 9.2% of cases. The best treatment regime included three courses of
Ukrain at 2-week intervals.
PMID- 10190080
TI - Evaluation of the efficacy of Ukrain in the treatment of breast cancer: clinical
and laboratory studies.
AB - The aim of this study was to evaluate the efficacy of different doses of Ukrain
in the treatment of 75 breast cancer patients. Patients were divided into three
groups. Group I (25 patients) and group II (25 patients) were treated with 50 mg
and 100 mg Ukrain, respectively, before surgery. The remaining 25 patients served
as controls (no Ukrain treatment). Both clinical observations and laboratory
parameters indicate that both doses of Ukrain tested had a similar beneficial
effect on patient outcome and may be indicated for presurgical treatment of
patients with breast cancer.
PMID- 10190081
TI - Ukrain and hyperthermia treatment in a patient with Ewing's sarcoma (case
report).
AB - A 10-year old girl with Ewing's sarcoma in the right femur was treated with
Ukrain and hyperthermia. Six weeks after the first therapy series, computer
tomography showed that progress of the disease had been halted. Following two
more therapy series no negative changes could be detected.
PMID- 10190082
TI - Ukrain treatment in a patient with stage IV neuroblastoma. A case report.
AB - A 22-month-old boy with stage IV neuroblastoma underwent laparotomy with tumor
removal and nephrectomy, followed by treatment with Ukrain. Two months later, a
remaining abdominal tumor, a retroperitoneal tumor (approximately 2 x 1 cm), and
lung, brain, pelvis, kidney, and distal femur metastases were found. Growth of
the neuroblastoma around the spinal cord and growth into the spinal canal was
also found. Ukrain was administered in 3-week therapy series with 3-week pauses
between each series. Some tumors disappeared, others were smaller, and growth
stopped in the remaining tumors. Various metastases were no longer detectable.
PMID- 10190083
TI - The influence of glucose, succinate, pH of the medium and higher temperature on
the cytotoxic activity of the preparation Ukrain.
AB - Cells of ascitic forms of Ehrlich's carcinoma and sarcoma 37 transplanted into
C57BI/6 mice were used to study the influence of glucose, succinate, and pH of
the medium on the cytotoxic activity of the preparation Ukrain. Viability of
cells was estimated by the method of intravital staining with tripan blue after
the incubation of cell suspension in the presence of the preparation (1.05 x 10(
5) mol and 1.69 x 10(-4) mol). It was established that glucose (5 mmol) reduces
the cytotoxic activity of Ukrain, while succinate (5 mmol) increases it. The
activity of the preparation was practically absent at pH 6.1-6.7 of the
incubation medium and was at a maximum at pH 7.3-8.0. A temperature of 41.5
degrees C has no influence on the effectiveness of Ukrain.
PMID- 10190084
TI - Macrophage stimulation and antitumor effect of Ukrain.
AB - It has previously been demonstrated that Ukrain administration (0.5 mg in mice of
20 g, five times) to A/Sn mice results in retardation of HA-1 tumor growth in the
liver and a prolongation of lifespan compared with untreated controls. In the
present study Ukrain was tested as a macrophage stimulator in intact mice and
animals with HA-1 hepatoma. There were no changes to the carbon particles
phagocytosis rate in the case of a single administration of Ukrain to intact
mice. Significant secretion of procathepsin B into ascitic fluid was shown in
tumor mice as well as marker enzyme of macrophages beta-hexosaminidase activity,
suggesting an influx of macrophages into ascites. Single Ukrain administration
increased this index, and repeated drug injections were followed by a tendency to
normalization of secretion. The cytolytic effect of Ukrain against tumor cells
(as a result of macrophage stimulation) is the most probable mechanism of its
antitumor action, but this suggestion needs further experimental evidence with
special attention paid to the balance of proteinases and endogenous proteinase
inhibitors.
PMID- 10190085
TI - The influence of Ukrain on the growth of HA-1 tumor in mice: the role of cysteine
proteinases as markers of tumor malignancy.
AB - The influence of Ukrain (exerting a malignotoxic effect in vivo according to
Nowicky J.W. et al [1]) on the growth of Hepatoma A (HA-1) tumors in mice and
cysteine proteinases as markers of tumor growth and malignancy was studied.
Ukrain administration (0.5 mg per mice of 20 g, in each of 5 i.p. injections)
resulted in a reproducible and significant retardation of HA-1 tumor growth in
the liver and a prolongation of lifespan compared with the untreated control.
Repeated Ukrain administration to mice increased the number of macrophages in
ascites, decreased the number of tumor cells, and concomitantly reduced the
increased level of monocytes in peripheral blood. In ascitic cells the specific
activity of cathepsin B was higher than in the intact liver and was not
influenced by Ukrain; activity of cysteine proteinases studied in ascitic fluid
was much higher than that in serum. Tumor growth was followed by a decrease in
cathepsin B activity in the liver and serum at day 10. Ukrain administration has
a tendency to normalize the disturbances of cathepsin B activity during tumor
development. The cathepsin L activity changes in ascitic fluid were more
impressive than those of cathepsin B, indicating the special role of this
cysteine proteinase in HA-1 tumor growth and invasiveness. The role of cysteine
proteinases as markers of tumor malignancy and invasiveness is discussed.
PMID- 10190086
TI - Study of the antitumor effect of Ukrain: the role of macrophage secretion of
alpha-1-proteinase inhibitor.
AB - The positive antitumor effect of Ukrain was shown following i.m. injection of a
mixture of this drug with Krebs-2 carcinoma cells to CBA mice. The protective
effect was suggested to be a result of the influx of macrophages into the site of
Ukrain injection. In contrast, contralateral administration of Ukrain had a
negative effect, confirming our hypothesis that Ukrain attracts cytolytic
macrophages. In the murine HA-1 hepatoma model treated by single or repeated
Ukrain injections, a moderate positive effect of Ukrain was related to increased
macrophage (alpha-1-proteinase inhibitor (PI) secretion. The role of tumor cells
and macrophages in the secretion of PI (the main inhibitor of serine proteinases)
during tumor development is discussed.
PMID- 10190087
TI - Comparative in vitro study of the effects of the new antitumor drug Ukrain and
several cytostatic agents on the thiol groups in the tissue of Guerin carcinoma
and its resistance to cisplatin variant.
AB - A comparative in vitro study between the effects of Ukrain (a new synthetic
thiophosphoric acid derivative of great celandine alkaloids) and alkylating
antitumor drugs cyclophosphamid and cisplatin on total thiol content in Guerin
carcinoma, Guerin/cis-DDP carcinoma, and in animal livers was carried out. It is
shown that Ukrain action on thiol groups in Guerin carcinoma tissue does not
differ from that of cyclophospamid and cisplatin to both of which Guerin
carcinoma is very sensitive. Once tumor resistance to cisplatin has developed,
cisplatin does not react with tumor thiol groups and cyclophosphamid reactions
with tumor thiol groups decrease. Reactions of Ukrain with thiol groups of
cisplatin resistant tumors increase. This indirectly indicates the increase of
tumor sensitivity to this drug. Therefore, the cytotoxicity of Ukrain is similar
to that of known antitumor drugs and can probably overcome the cisplatin
resistance of the tumor.
PMID- 10190088
TI - Morphometric and kinetic analysis of the growth of experimental sarcoma-45 in the
presence of Ukrain.
AB - The effect of the antitumor agent Ukrain on the growth kinetics of the
experimental tumor sarcoma-45 was studied by correlation analysis. Sarcoma-45 was
implanted into 28 Wistar rats in the subcutaneous layer of a lateral site of the
trunk. Fourteen animals received i.v. Ukrain every other day in a dose of 30
mg/kg (0.1 LD50). The other 14 rats served as controls. Macromorphometry of the
tumor nodes of sarcoma-45 was carried out every day in both groups. Statistical
analysis of morphometric data and plotting of histograms were performed.
Regression equations were selected and their parameters determined. A
mathematical model was assessed. The effectiveness of Ukrain treatment was
analyzed using the equivalent exponent method. Ukrain was proved to be an
effective antitumor agent on biological and mathematical models in accordance
with standardized instructions for screening.
PMID- 10190089
TI - Study of acute toxicity of Ukrain in rats after intravenous injection.
AB - The acute toxicity of i.v. Ukrain injection in rats was studied. The
interrelation between toxicity (death of animals) and dosage was determined by
nonlinear regression method. White blood count (WBC) in peripheral blood, weight
of animals, and weight of major organs were determined in animals during all
stages of investigation. Morphological studies of toxic changes in 40 different
organs of rats were performed on macro- and microscopic levels.
PMID- 10190090
TI - Six-week treatment with Ukrain in rabbits. Part I: Morphological parameters.
AB - This study was performed to evaluate the effect of 6-week treatment with Ukrain
in doses of 0.3, 1.5 and 3.0 mg/kg i.v. on the morphological and biochemical
parameters of peripheral blood and morphology of body organs in rabbits. Ukrain
application did not change the body organs and total body weight. The drug did
not affect biochemical parameters of peripheral blood, except for a minor
reduction in the total plasma level and increases in serum uric acid and urea
indicating enhanced catabolism of proteins. The peripheral erythrocyte and
leukocyte counts were not altered, whereas the percentages of lymphocytes,
monocytes, and eozynophils were increased after higher doses of Ukrain. An
increase in rod neutrophils and a decrease in the percentage of segmented
neutrophils were also noted. These observations indicate a lack of organ toxicity
following long-term treatment with Ukrain.
PMID- 10190091
TI - Six-week treatment with Ukrain in rabbits. Part II: Serum levels of gonadal
hormones.
AB - The effect of 6-week treatment with Ukrain at doses of 0.3, 1.5, and 3.0 mg/kg
i.v. on the serum levels of steroid hormones, i.e., estradiol, testosterone, and
progesterone, was studied in rabbits of both sexes. It is demonstrated that
Ukrain treatment exerts minor changes in serum hormone levels. The level of
estradiol was increased in the serum of male rabbits following Ukrain treatment
only at the dose of 1.5 mg/kg i.v. Similarly, the estradiol serum level was
increased after Ukrain given at 1.5 mg/kg i.v. in female rabbits. In male rabbits
Ukrain application at 0.3 mg/kg i.v. increased the serum testosterone level.
Serum testosterone levels were not altered following Ukrain administration up to
3.0 mg/kg i.v. in female rabbits. Ukrain raised the serum progesterone levels in
male rabbits at the doses of 0.3 and 3.0 mg/kg i.v. in females, only the highest
dose of Ukrain produced a significant increase of serum progesterone.
PMID- 10190092
TI - Six-week treatment with Ukrain in rabbits. Part III: Serum levels of thyroid
hormones.
AB - The influence of 6-week treatment with Ukrain at doses of 0.3, 1.5 and 3.0 mg/kg
i.v. on serum levels of thyroid hormones, i.e., thyroxine and triiodothyronine,
was studied in rabbits of both sexes. Ukrain affected the serum levels of both
hormones in males. An increase in the thyroxine level was found after Ukrain used
at a dose of 1.5 and 3.0 mg/kg i.v., whereas increased triiodothyronine was noted
when Ukrain was given at all studied doses. In females the thyroxine level was
not altered by Ukrain administration, whereas the triiodothyronine concentration
was increased following Ukrain at 0.3, 1.5 and 3.0 mg/kg i.v. it is probable the
altered thyroid hormone levels as a result of Ukrain application may contribute
to the drug's potent immunomodulatory action.
PMID- 10190093
TI - Preliminary pharmacokinetic studies of Ukrain in rats.
AB - Ukrain (thiophosphoric acid derivative of Chelidonium majus L. alkaloids) was
administered to rats i.p. at a dose of 28 mg/kg (equivalent to 0.1 LD50). A high
performance liquid chromatography (HPLC) method for rapid determination of Ukrain
in plasma has been described. It was found that Ukrain rapidly penetrated into
the plasma of the rats and the elimination of the drug from the plasma was
slower. The results obtained were as follows: absorption rate constant ka =
0.0432 [min-1]; elimination rate constant K = 0.0113 [min-1]; drug half-life t1/2
= 61.32 min; actual concentration of Ukrain in the plasma C = 33 e-0.0113t - 39 e
0.0432t [microgram/ml]; and delay in drug absorption T0 = 5.23 min.
PMID- 10190094
TI - Effect of intermittent three-month treatment with different doses of Ukrain on
subregional femoral bone mineral density of sexually mature female rats.
AB - Sexually mature but still growing female Wistar rats received i.p. injections of
Ukrain (7, 14 or 28 mg/kg in a volume of 0.5 ml/100g) every other day for 10
days, followed by a 10-day break, and this procedure was performed five times.
The control animals received the same volume of injected water. At the end of the
experiment the rat right femora were harvested and the bone densitometric
parameters of the entire bone, distal metaphyseal and basicervical subregions
were assessed using the dual-energy X-ray absorptiometry (DXA) densitometric
method. No significant changes were observed in the bone mineral density in
experimental groups in comparison with control animals that received the vehicle.
A slight decrease in the bone mineral content value was observed in the distal
metaphyseal region in animals that were treated with the highest dose of Ukrain.
PMID- 10190095
TI - Effect of intermittent three-month treatment with different doses of Ukrain on
subregional bone mineral density of the femur of ovariectomized rats.
AB - Ukrain, thiophosphoric acid alkaloid derivative from Chelidonium majus L., was
administered i.p. to ovariectomized rats in doses of 7, 14 and 28 mg/kg every
other day for 10 days, followed by a 10-day break, and the procedure was
performed five times. At the end of long-term treatment with Ukrain (24 h after
the last dose of the drug) the rats' right femora were harvested and the bone
densitometric parameters of the whole bone and distal metaphyseal and
basicervical subregions were assessed using the dual-energy X-ray absorptiometry
(DXA) densitometric method. The present results show a decrease in bone mineral
density in groups of ovariectomized rats that received 7 mg/kg and 14 mg/kg of
Ukrain versus untreated ovariectomized animals. Administration of Ukrain at a
dose of 28 mg/kg did not significantly alter bone parameters of ovariectomized
rats.
PMID- 10190096
TI - Modification of antinociceptive action of Ukrain by endogenous nitric oxide in
the writhing syndrome test in mice.
AB - The effects of L-arginine, the physiological precursor of nitric oxide (NO), and
inhibitors of NO-synthase on the antinociceptive action of Ukrain (4.75, 9.5, and
19.0 mg/kg i.p.) were investigated using the writhing syndrome test in mice. It
was found that L-arginine (0.1 or 1.0 mg/kg i.p.) significantly decreased or
enhanced the antinociceptive effect of Ukrain, depending on the combination
administered. In addition, the inhibitors of NO-synthase NG-nitro-L-arginine
methyl ester (L-NAME) (1.0 and 10 mg/kg i.p.), 7-nitroindazole (1.0 mg/kg i.p.)
and NG-monomethyl-L-arginine acetate (L-NMMA) (1.0 mg/kg i.p.) significantly
enhanced Ukrain-induced antinociception. These results suggest that endogenous NO
can modify the antinociceptive effect of Ukrain.
PMID- 10190097
TI - Interaction between Ukrain and Naltrexone in the writhing syndrome test in mice.
AB - The interaction between Ukrain and Naltrexone, a nonselective opioid receptor
antagonist, was studied in the 'writhing syndrome' test in mice. Naltrexone (1
mg/kg s.c.) was administered i.p. 30 min before Ukrain (2.375, 4.75, 9.5 and 19
mg/kg). In addition, the antinociceptive properties of Ukrain and Naltrexone in
10-day treatment in mice were studied. The results show that the antinociceptive
effect of both single dose and prolonged administration of Ukrain is completely
antagonized by Naltrexone.
PMID- 10190098
TI - A comparative evaluation of the influence of the complex drug Ukrain and its
components on the effects of radiation.
AB - The development of cancer therapy is associated with an increased application of
therapeutic schedules that combine radiation and different drugs. Ukrain is a
promising drug proved to be efficient in the treatment of different tumors when
used either before, during or after radiation therapy. Therefore, the issue of
the influence of this drug on the effects of radiation is of interest. In
previous studies, the ability of Ukrain to ameliorate the harmful consequences of
irradiation was demonstrated. Ukrain is a semi-synthetic thiophosphoric
derivative of Chelidonium majus L. alkaloids, i.e., it is a complex preparation.
Therefore, it is necessary to elucidate which of its components are the active
agents that mediate its antiradiation effects. The aim of this study was to
compare the radioprotective effects of Ukrain and its components in experiments
with animals irradiated by doses within a broad range (from LD50/30 to LD100/30).
A total of 1,240 outbred male white mice were gamma-irradiated with an IGUR
apparatus using 137Cs as the radiation source. Doses applied ranged from 5.25-7.5
Gy with a 0.75 increment between dosages. Dose rate was 1.41 Gy/min. The
experiments have shown that the radioprotective effects of Ukrain are far
superior to all its components taken separately, both measured by survival of
mice irradiated by different doses, and by the protection coefficient a. These
observations suggest that the influence of Ukrain on radiation effects does not
result from the antiradiation properties of its components but rather from the
concerted action of the specific combination found in Ukrain.
PMID- 10190099
TI - The influence of the novel drug Ukrain on hemo- and immunopoiesis at the time of
its maximum radioprotective effect.
AB - Several studies have demonstrated that when Ukrain, a complex preparation of
great celandine alkaloids, is used as a preventive agent it increases the
survival of animals exposed to whole body gamma-irradiation and enhances the
restoration of hemopoiesis. The aim of this study was to describe qualitative and
quantitative changes in hemopoietic precursor cells and in myelokaryocytes and
leukocytes in the blood caused by Ukrain from its administration to the time the
maximal radioresistance potential of the organism is reached. Ukrain was
administered i.p. at the dose of 0.2 mg/kg, 24 h prior to investigation. Control
animals were injected with saline. Colony-forming units (CFU) were counted in the
spleen and bone marrow of the mice, and myelokaryocyte and leukocyte (lymphocyte
and granulocyte) counts were determined. The results of this study suggest that
Ukrain causes qualitative and quantitative alterations in different pools of
hemopoietic cells (stem cells, proliferating cells, maturing cells, and competent
cells). These alterations affect the size of the stem cell pool, the kinetics of
stem cell proliferation, the direction of their differentiation pathways, the
rate of circulation of stem cells and precursor cells, the efficiency of
recolonization of cell-depleted sites, and other parameters, which in effect
modify standard responses of hemopoiesis and immunogenesis to irradiation so that
the radioresistance of the whole organism increases.
PMID- 10190100
TI - A study of the influence of a novel drug Ukrain on in vivo effects of low-dose
ionizing radiation.
AB - The extrapolation of data obtained with lethal doses of radiation to evaluating
low doses, i.e., those not causing immediate death, seems to be unjustified.
Thus, models have to be developed that are based on integral parameters (such as
the survival of experimental animals), easy to perform, and permit screening
procedures to be carried out within 30 days in order to make screening efficient.
Two hundred and sixty outbred male white mice were irradiated with a 1 Gy dose at
a 0.75 Gy/min. To produce a model of acute infection, the animals were infected
by tularemia (2 x LD50) using Gaiskiy-15 strain of the infectious agent. A viral
disease was produced by infecting mice by the equine encephalomyelitis (EEM)
virus. The animals were infected 24 h after irradiation. The survival of animals
was used as an end point. Such conditions are most prevalent in areas
contaminated by radioactivity. Irradiation prior to infection was found to
decrease the survival rate of experimental animals. Preventive administration of
Ukrain increased the survival rate of experimental animals. On the whole, the
results suggest that Ukrain deserves the attention of experts in radioprotection.
PMID- 10190101
TI - A study of the influence of different types of radioprotectors on the survival of
mice treated with ionizing radiation over a wide dose range.
AB - The subject of this study is the influence of the preventive administration of
cystamine, naphthysin, Ukrain, Lymphokinin, Prodigiosan, and polyribonate on the
30-day survival of mice subject to doses of ionizing radiation ranging from
LD50/30 to LD100/30. Conventional radioprotectors were shown to prevent the death
of experimental animals irradiated with doses ranging from LD70 to LD100/30 but
were inefficient as a means of preventing mortality at doses with a medium lethal
effect. In contrast, the bioregulators Ukrain and Lymphokinin were more potent at
doses ranging from LD50 to LD70/30 (1.5 times more potent than conventional
radioprotectors). Polyribonate and Prodigiosan were the least potent. These
findings are discussed with respect to the appropriateness of developing
pharmacological means which could protect organisms from different degrees of
radiation-induced damage. The need to modify the criteria for the selection of
potential radioprotectors is emphasized.
PMID- 10190102
TI - [Vibrio cholerae temperate phage O139: characteristics and role in changing
expression of chromosomal virulence genes].
AB - Restriction analysis of temperate cholera phage 139 isolated from Vibrio cholerae
P16064, serogroup 0139, showed its DNA to be double-stranded linear with cohesive
terminals. DNA-DNA hybridization on nylon membranes revealed that many V.
cholerae strains of serogroup 0139 isolated in different regions contained a
temperate cholera phage 139 in their genomes. Southern blot hybridization of
chromosomal DNA PST-fragments with phage probe showed that the temperate phage
139 was identical to the temperate phage of serogroup II V. eltor. The phage
integrated in the chromosome near genes encoding motility (mot) and production of
the capsule (cap) and purine (pur). Phage genome is apparently responsible for
instability of cap, pur, and mot genes whose products are important for the
development of an infectious process in cholera.
PMID- 10190103
TI - [Comparative study of various methods for determining Vibrio cholerae
toxigenicity].
AB - Testing of 138 Vibrio cholerae strains for gene determinants responsible for the
production of cholera enterotoxin by the polymerase chain reaction (PCR) and gene
probing using molecular CT-probe showed good correlation of the results of
different methods and correlation of these data with studies of V. cholerae
strain virulence in vivo and in hemolytic activity test. The advantages of PCR in
rapid assessment of the toxigenicity and epidemic significance of V. cholerae
strains are demonstrated.
PMID- 10190104
TI - [Expression of secreted guanyl-specific ribonuclease genes from Bacillus
intermedius and Bacillus pumilus in Bacillus subtilis cells].
AB - Plasmids with whole genes for ribonucleases from B. intermedius (binase) and B.
pumilis (RNase Bp) assembled with the whole gene of barstar, a specific
intracellular inhibitor, are constructed. The resultant plasmids pMZ55 and pMZ56
effectively express binase and RNase Bp genes in B. subtilis cells. A medium for
maximum expression of RNase genes by recombinant strains is developed. The
expression of binase and RNase Bp genes in B. subtilis cells is negatively
regulated by exogenic inorganic phosphate.
PMID- 10190105
TI - [Cloning and expression of a serine proteinase gene from Thermoactinomyces sp. in
Bacillus subtilis cells].
AB - A gene coding for thermostable serine protease from Thermoactinomyces sp. K50 is
cloned and expressed in Bacillus subtilis cells. Restriction map of cloned DNA
fragment is determined. Thermostability and temperature optimum of proteolytic
activity of the cloned gene product are lower than those of the natural
proteinase of Thermoactinomyces sp. K50. Serine protease, a product of cloned
gene, is highly sensitive to proteolysis and its degradation can be prevented by
Ca2+ ions.
PMID- 10190106
TI - [Contribution of determinants, located in Bacillus anthracis chromosomes, in
realizing the pathogenic properties of the pathogen].
AB - Comparative study of virulence of B. anthracis strains harbouring pXO1 and pXO2
plasmids in mice and guinea pigs showed that among six B. anthracis strains,
three were 100-1000 times less virulent for guinea pigs. Genetic construction of
B. anthracis strains using transduction and conjugation transfer of resident
plasmids permitted us to rule out the effects of modified pXO1 and pXO2 replicons
and to prove the existence of nonidentified chromosome locuses responsible for
the development of an infectious process in anthrax, along with plasmid
determinants of virulence.
PMID- 10190107
TI - [Strain differentiation of the Newcastle disease virus by reverse transcriptase
polymerase chain reaction and sequencing population exchange].
AB - A system for detection and strain differentiation of Newcastle disease virus
(NDV) by reverse transcription of polymerase chain reaction (RT-PCR) (isolation
of RNA, choice of primers for nested PCR, and purification of PCR products) and
sequencing is developed and optimized. A nucleotide sequence of gene F site,
coding for the F2/F1 cleavage site of F0 fusion protein and including several
hypervariable regions, is determined for 10 Russian strains and vaccine strains.
The data indicate a replacement of NDV populations in Russia and a rapid
evolution of the virus. The origin of pathogenic NDV strains which have been
circulating up to the present time is still unknown.
PMID- 10190108
TI - [Detection of the hog cholera virus using the polymerase chain reaction].
AB - A rapid and highly sensitive method for detecting hog cholera virus (HCV) based
on a reverse transcription of the polymerase chain reaction (RT-PCR) is
developed. Primers complementary to the most homologous sites of virus genome in
an area coding the precursor for glycoproteins gp44/gp48 are selected. Detection
of the virus in pathological material by the RT-PCR showed that use of these
primers in amplification allows detection of different HCV strains.
PMID- 10190109
TI - [Development of a method for alkaline extraction of DNA from Brucella for
diagnosing brucellosis using the polymerase chain reaction].
AB - Several methods of alkaline extraction of chromosome DNA from Brucella in the
presence of 50 microliters model diagnostic material blood serum are developed
for the diagnosis of brucellosis by the polymerase chain reaction (PCR). These
methods are based on the capacity of NaOH to effectively denature proteins and
destroy Brucella cell wall, thus isolating the genome DNA without exposure to
proteolytic enzymes, detergents, deproteinization, or pH neutralization. The
first method consists in alkaline lysis by 0.2-1.0 M NaOH followed by DNA
precipitation with two ethanol volumes in the presence of 0.1 M NaCl, washing of
the resultant precipitate in 80% ethanol, drying of the precipitate, and
dissolving in distilled water. The second method includes alkaline lysis in the
presence of 0.3 M NaCl with NaOH concentrations of 0.5-4.3 M and the stages of
DNA sedimentation, washing of precipitate, its drying and dissolving similar to
those in alkaline lysis. The third method consists in alkaline lysis
precipitation by 0.2-05 M NaOH in the presence of 0.1 M NaCl and 64% ethanol,
followed by DNA preparation stages similar to those in alkaline lysis. The best
results were achieved by alkaline lysis in the presence of 0.3 M NaCl at NaOH
concentrations of 0.7 and 2.1 M, which meant theoretical levels of sensitivity
140 and 86 Brucella cells, respectively.
PMID- 10190110
TI - [Plasmid pCL1 and antimicrobial activity of a strain of Bacillus sp. 62].
AB - The 60 kb plasmid pCL1 isolated from Bacillus sp. 62 confers antibacterial
activity. Bacteria cured from pCL1 by ethidium bromide treatment loose the sign.
Transformation of cured from by pCL1 restores the initial phenotype, while
plasmid transfer into B. subtilis 168 does not confer antibacterial activity,
which indicates the significance of chromosome locuses in the formation of this
sign.
PMID- 10190111
TI - Evaluation of three different commercial procedures for quantifying human
immunodeficiency virus type-1 RNA levels.
AB - A branched DNA method for the quantification of human immunodeficiency virus type
1 (HIV-1) RNA levels (Quantiplex HIV RNA 2.0) was compared with a reverse
transcriptase-coupled polymerase chain reaction method (Amplicor HIV-1 Monitor)
and a nucleic acid sequence-based assay (Nuclisens HIV-1 QT) in plasma samples
from a group of HIV-1 seropositive patients. We found a high correlation between
Nuclisens and Quantiplex (r = 0.89; p < 0.001) and between Amplicor and
Quantiplex (r = 0.94; p < 0.001), a shift of RNA viral load to higher Nuclisens
and Amplicor values compared with the Quantiplex results and a significant
positive correlation (rS = 0.60; p < 0.001) between the p24 antigen level and the
RNA viral load determined with the Quantiplex assay. We also found higher
sensitivities of the Nuclisens and the Amplicor procedures compared with the
Quantiplex assay. The total sensivity of the Quantiplex assay in our study was
70% whereas that of the p24 antigen was only 29%.
PMID- 10190112
TI - Recurrence of hepatitis C virus infection after orthotopic liver transplantation:
role of genotypes.
AB - In this study, we evaluated the correlation between alanine aminotrasferase
levels and hepatitis C virus genotypes in liver transplant patients. We studied
18 patients who had undergone orthotopic liver transplantation because of end
stage cirrhosis (n = 9) or hepatocellular carcinoma (n = 9) hepatitis C virus
related. Serum HCV-RNA testing was performed monthly on all the 18 series of
serum samples from the first week after liver transplant until the end of the
follow up, this period ranging from 1 to 39 months. After liver transplantation,
serum HCV-RNA was detected in 14 patients (78%). Of the 8 patients infected with
subtype 1b. 1 remained asymptomatic, 2 developed acute liver failure and 5
developed chronic hepatitis. In patients infected with types 1a (Choo et al.,
1989), 2a (Choo et al., 1989), with a mixed infection 1b/3 (Kuo et al., 1989) or
with an undetermined genotype, significant laboratory abnormalities were not
observed. Recurrence of hepatitis C virus infection after liver transplantation
is common, and recurrent hepatitis occurs in 50% of cases. Genotype 1b appears to
be associated with a higher rate of recurrent hepatitis, compared to other
genotypes.
PMID- 10190113
TI - Analysis of antibody response to synthetic peptides derived from the fusion
protein of measles virus.
AB - A computer program combining of hydrophilicity, flexibility, surface probability,
secondary structure and antigenic index parameters of the amino acid sequence of
measles virus (MV) fusion protein was used to select four possible epitopes.
Rabbits were immunized with the synthesized peptides conjugated to purified
protein derivative using the homobifunctional cross-linker bis-sulfosuccinimidyl
suberate. Immune stimulating complexes were prepared with the peptides conjugated
to the purified protein derivative carrier using a dialysis method. All antisera
raised in rabbits against the peptide conjugates had a high titer to the
homologous peptides and reacted well with denatured MV as tested by plate ELISA.
None of the sera had neutralizing antibody. Human sera positive for MV antibody
reacted strongly with the synthesized peptides indicating that the selected
locations function as partial antigenic sites. Antisera against peptide
conjugates reacted weakly in immunofluorescence and none of these antisera
reacted with purified MV proteins in Western blot. The results obtained in this
study indicated that although the computer program could not predict epitopes
important for the neutralization of the MV, the predicted epitopes are useful for
detecting antibodies against MV.
PMID- 10190114
TI - A study of an experimental infection of sheep with Mycoplasma agalactiae.
AB - The results of an experimental infection of sheep with a field strain of
Mycoplasma agalactiae are reported. Six sheep, seronegative to M. agalactiae were
used: three sheep were inoculated by the conjunctival route (group A) and three
sheep intranasally (group B). The clinical signs were observed 20 days after
infection but the shedding of Mycoplasma agalactiae, particularly from the nasal
route and with milk, started a few days post infection (d.p.i.) (1st d.p.i. and
9th d.p.i. respectively). Antibody titers were first detected after 28 d.p.i. in
group B and after 35 d.p.i. in group A.
PMID- 10190115
TI - Granulocyte-macrophage colony stimulating factor modulates the production of TNF
alpha by differentiated U937 cells infected with Leishmania major.
AB - In this work, the production of tumor necrosis factor alpha (TNF alpha) during
interaction of human phagocytes with the intracellular parasite Leishmania major
was further investigated. The human monocytic cell line U937, differentiated with
a combination of 1 alpha, 25 dihydroxyvitamin D3 (VD) and retinoic acid (RA), or
with granulocyte macrophage colony stimulating factor (GM-CSF) was used.
Differentiated U937 cells were infected with Leishmania major promastigotes, and
TNF alpha was assayed in cell culture supernatants. It was found that the
cytokine was produced only by U937 cells differentiated with VD/RA and further
incubated with GM-CSF and LPS or interferon gamma (IFN gamma). L. major induced
TNF alpha production only in the presence of GM-CSF. No direct relationship was
found, however, between production of TNF alpha and resistance of differentiated
U937 cells to infection with L. major.
PMID- 10190116
TI - Molecular typing of Candida spp. by random amplification of polymorphic DNA and
analysis of restriction fragment length polymorphism of ribosomal DNA repeats.
AB - Random amplification of polymorphic DNA (RAPD) using an arbitrary oligonucleotide
primer (5'-CGGTGCGACG) and analysis of restriction fragment length polymorphism
of ribosomal DNA (rDNA-RFLP) after digestion of genomic DNA with restriction
endonuclease EcoRI were investigated as tools for genotypic delineation beyond
the species level of 91 Candida clinical isolates and four reference strains
including 33 Candida albicans, 19 Candida tropicalis, 22 Candida krusei and 21
Candida (Torulopsis) glabrata. Results indicated that both techniques can be
useful for typing isolates of the above species, although showing a variable
discriminative potential with different species. As compared to RAPD
fingerprinting, the discriminative potential of rDNA-RFLP appeared to be highest
for C. albicans and lowest for C. glabrata, being overall similar for C. krusei
and identical for C. tropicalis. A comparative analysis of the results obtained
with the two typing techniques showed that, except for C. tropicalis, they were
able to provide non-redundant information, and that their use in combination
could enhance the discriminative potential for delineation among C. glabrata and
C. krusei isolates.
PMID- 10190117
TI - Use of RAPD-PCR fingerprinting to detect genetic diversity of soil Streptomyces
isolates.
AB - Random amplified polymorphic DNA (RAPD) was used for identification and
assessment of genetic diversity between isolates of Streptomyces from soil.
Genomic DNA from 18 Streptomyces isolates and 2 reference strains were amplified
using four different 10-mer primers. Different DNA fingerprinting patterns were
obtained for all the isolates. Electrophoretic and cluster analysis of the
amplification products revealed incidence of polymorphism among the isolates and
none of them was identical to the reference strains although there were some
common amplification bands. Two highly divergent groups were determined among the
isolates. The results indicate that RAPD is an efficient method for
discriminating and studying genetic diversity of Streptomyces isolates.
PMID- 10190118
TI - An abnormally long HIV-1 env DNA PCR product due to altered sequences of primer
binding sites.
AB - To investigate the generation of an abnormally long HIV-1 env PCR DNA product the
latter was cloned and sequenced followed by sequence analysis of HIV-1 primer
binding sites. We found that the formation of an abnormally long PCR product was
due to HIV-1 env sequence alteration (a) in the reverse primer binding site
resulting in faulty primer binding and (b) downstream from the forward primer
sequence resulting in a new binding site with reverse complementary sequence with
respect to the forward primer at the opposite end of the PCR product. Both
changes led to amplification of a longer PCR product with forward primer alone.
Our results indicate that the HIV-1 genetic diversity in the env gene can lead to
amplification of a specific PCR product of unexpected size which can be
disregarded in the absence of its cross-validation.
PMID- 10190119
TI - Haemagglutination and haemolysis by oral Fusobacterium nucleatum.
AB - Haemagglutination and haemolytic activity of 80 Fusobacterium nucleatum isolates
from human and animal origin, on different human blood types was evaluated. All
the isolates were able to agglutinate erythrocytes and the most were either alpha
haemolytic or beta-haemolytic. No specificity between haemolysin or
haemagglutinin and blood type was observed. Haemagglutination activity was
inhibited when D-galactose, D-lactose or D-raffinose were used. Haemagglutination
and haemolysis may be important factors in the pathogenesis of human and animal
periodontal diseases.
PMID- 10190120
TI - Influence of aminoacid requirement on the growth of Bifidobacterium globosum
strains.
AB - A general procedure has been devised for the determination of amino acid
requirements in Bifidobacterium globosum strains, based upon identification of
individual amino acids singularly deprived of the defined synthetic medium. In
the plasmid-positive and plasmid-negative clones of RU 809 and T 19 strains, we
found a correlation between the presence of plasmid and L-leucine auxotrophy.
This characteristic is not shared by the other 145 strains, 26 of which are
plasmid-positive, of the B. globosum species.
PMID- 10190121
TI - L-leucine auxotrophy in Bifidobacterium globosum.
AB - The enzymes involved in the biosynthetic pathway of L-leucine were studied in
plasmid-negative and plasmid-positive clones derived from the RU 809 strain of
the Bifidobacterium globosum species. The growth of plasmid-positive clones in
synthetic medium required L-leucine. We have shown that no detectable activity of
the beta-isopropylmalate dehydrogenase enzyme was present in plasmid-positive
clones, whereas detectable and significant activity of this enzyme was found in
plasmid-negative clones. The lack of activity of the beta-isopropylmalate
dehydrogenase enzyme is considered responsible for the L-leucine auxotrophy in
the plasmid-positive clones.
PMID- 10190122
TI - Distribution and possible functions of neuropeptides in the nervous system.
AB - Neuropeptides have now been localized throughout the nervous system. This talk
focuses attention on (1) the interplay of peptides and other neurotransmitter
systems in the hypothalamus--median eminence--pituitary gland. The multiplicity
of neurochemicals is perceived to be responsible for the integrated control of
pituitary hormone releasing factors; (2) the role of neuropeptides in the
regulation of cardiovascular function in the hypothalamus-preoptic area. We
investigated the effects of discrete intrahypothalamic injections of a variety of
peptides on blood pressure and heart rate. We concluded that neuropeptides have a
diversity of central cardiovascular actions and that not all areas containing a
given peptide respond with cardiovascular change when the peptide is injected.
Also, peptide specific actions originating within the same nucleus have been
demonstrated, and the same peptide may have different vascular effects in
different segments of the same nucleus; (3) the colocalization of neuropeptides
with other classical neurotransmitters. We have found modulatory behavioral
effects ("boxing") of combinations of transmitters and peptides injected into the
postsynaptic site in the brain.
PMID- 10190123
TI - [Cholinergic neural regulation of regional cerebral blood flow].
AB - Local metabolites have long been considered to play an important physiological
role in regulating regional cerebral blood flow (rCBF). However, the evidence
reviewed here emphasizes that the regulation of rCBF by central cholinergic
nerves is independent of regional metabolism. Activation of the intra cranial
cholinergic fibers originating in the nucleus basalis of Meynert (NBM) and septal
complex releases acetylcholine in the cortex and hippocampus, which results in
vasodilation and an increase in rCBF in the cortex and hippocampus via activation
of both muscarinic and nicotinic acetylcholine receptors. Cutaneous sensory
stimulation activates the cholinergic nerves originating from the NBM to enhance
rCBF. The increase in rCBF at the defuse cortices during walking appears to
include an excitation of this NBM-originating cholinergic vasodilation system.
Other various inputs to the NBM may have a similar effects to enhance rCBF via
activation of that cholinergic system, provided the stimulation is delivered
properly. Thus the combination of pharmacological and nonpharmacological
techniques may provide a balance in our attempts to improve cholinergic
replacement therapy.
PMID- 10190124
TI - [Neuroprotection by neurotrophic factors in apoptosis].
AB - During development, excess neurons are produced about half of which die. The time
of cell death (apoptosis) is limited to the period of formation of synapses with
the target cells, and the neurons which fail to obtain sufficient amounts of
trophic factor(s) released from the target cells are eliminated. This selection
system is considered to be a mechanism to ensure formation of a physiologically
relevant neuronal network. Mature neurons which correctly execute their
functions, however, undergo apoptosis in response to exogenous toxic stimuli.
Such stimuli may be responsible for neurodegenerative diseases. The mechanism
underlying cell death has been analyzed using in vitro model systems. In the
present communication, we used cultured rat cerebellar granule neurons, in which
low potassium concentration (LK+) in the medium induces apoptosis, and this
apoptosis is prevented by high concentration of potassium (HK+), BDNF. One of the
lipid-modifying kinases, phosphatidylinositol 3-kinase (PI3-K), is also activated
by trophic factors including neurotrophins. BDNF and high K+ prevented low K(+)
induced apoptosis via PI3-K. BDNF also promotes the survival of basal forebrain
cholinergic neurons cultured from postnatal 2-week-old (P2w) rats. The mechanism
of neuronal apoptosis induced by oxidative stress using CNS neurons and PC12
cells was investigated, and we found that generation of reactive oxygen species
(ROS) is highly associated with apoptosis. High oxygen induced neuronal
apoptosis, which was blocked by protein or RNA synthesis inhibitors. Neurotrophic
factors and Bcl-2 prevented this apoptotic cell death. Exposure to hydrogen
peroxide, lipid hydroperoxide or serum deprivation triggered apoptosis associated
with increased generation of ROS as determined using a ROS-specific fluorescent
probe. In cultured cerebellar granule neurons from 15-day-old wild-type and p53
deficient mice, we examine the role of p53 in regulating the life and death of
CNS neurons. When exposure of gamma-ray or bleomycin to neurons died in p53
dependent manner. These neuronal deaths were partially prevented by actinomycin D
or cycloheximide. The pycnotic nuclei observed in these dying neurons indicated
that cell death occurs via apoptosis. Although there are many evidences that p53
is involved in apoptosis in proliferating cells, it is interesting that p53 is
also involved in apoptosis in postmitotic neurons as shown in this study.
PMID- 10190125
TI - [Apoptosis and microglia].
AB - Microglia, macrophage-like cells in the central nervous system (CNS), are multi
functional cells; they play an important role in removal of dead cells or their
remnants by phagocytosis in the CNS degeneration and are one of important cells
in the CNS cytokine network to produce and respond to a variety of cytokines.
Although little is known about microglia in the normal CNS, it is obvious that
they are quickly activated in all acute pathological events including apoptosis,
neurodegeneration and inflammation. Activation of microglia in apoptosis is a
double-edged response; under severe apoptotic conditions microglia act as
scavengers removing tissue debris and inducing apoptosis in damaged cells,
whereas in more subtle injury they exert a surveillance function and might play a
protective role. The transformation of resting microglia into full blown
phagocytes is strictly regulated. To understand molecular basis of controlling
mechanisms of microglia in apoptosis, the study will need in vivo models. For
such purpose, we developed the brain-targeting gene delivery system using
immortalized microglia, which can facilitate investigation into the roles of
particular microglial genes in apoptosis and gene therapy of several brain
disorders.
PMID- 10190126
TI - [Oligodendrocyte cell death by caspase family proteases].
AB - Oligodendrocytes are myelin forming cells in mammalian central nervous system.
About 50% of oligodendrocytes (OLGs) undergo cell death in normal development. In
addition, massive OLG cell deaths have been observed in multiple sclerosis (MS).
Tumor necrosis factor (TNF) is thought to be one of the mediators responsible for
the damage of oligodendrocytes (OLGs). The addition of TNF-a to primary cultures
of OLGs significantly decreased the number of live OLGs in 72 h. Chemical
inhibitors Ac-YVAD-CHO (a specific inhibitor of caspase-1-like proteases)
enhanced the survival of OLGs treated with TNF-a, indicating that caspase-1
mediated cell-death pathway are activated in TNF-induced OLG cell death, caspase
11 is involved in activation of caspase-1. Oligodendrocytes from CASP-11
deficient mice are partially resistant to TNF-induced cell death. These results
suggest that the activation of caspases is crucial in TNF-induced OLG cell death
and inhibition of caspase family may be a novel approach to treat
neurodegenerative diseases such as MS.
PMID- 10190127
TI - [Apoptosis of astroglial cells].
AB - Astrocytes, the most abundant glial cell type in the brain, are considered to
have physiological and pathological roles in neuronal activities. We found that
reperfusion of cultured astrocytes after Ca2+ depletion causes delayed cell death
and that the Na(+)-Ca2+ exchanger in the reverse mode is responsible for this
Ca(2+)-mediated cell injury (Ca2+ paradox injury). The Ca2+ paradox injury of
cultured astrocytes is considered to be an in vitro model of ischemia/reperfusion
injury, since a similar paradoxical change in extracellular Ca2+ concentration is
reported in ischemic brain tissue. Furthermore, we demonstrated that heat shock
proteins, glutathione and calcineurin inhibitors protected astrocytes against
Ca2+ paradox-induced cell toxicity. We also observed DNA fragmentation, a typical
apoptotic ladder, 2-3 days after hydrogen peroxide exposure. In addition, laser
microscopic observation showed that reperfusion after the exposure to hydrogen
peroxide caused nuclear condensation of astrocytes. Hydrogen peroxide-induced
cell injury and DNA fragmentation were attenuated by the NF-kappa B inhibitor
ammonium pyrrolidinedithiocarbamate, 1,10-phenanthroline and a caspase 3
inhibitor. These findings suggest that astrocytes are one of the targets for ROS
and the oxidative stress-induced delayed death of astrocytes is at least due to
apoptosis.
PMID- 10190128
TI - [Modulatory mechanisms involved in the parasympathetic excitatory neuro-effector
transmission in the airway and gastrointestinal tracts--perspective for a new
drug creation].
AB - It is generally considered that dominant excitatory control of airway and
gastrointestinal tract is exerted by the parasympathetic nervous system, and the
transmitter output from the nerve terminals, mainly acetylcholine (ACh), is
modulated in many ways for example by ACh itself, prostaglandins E series (PGE)
neuropeptides and nitric oxide (NO). These modulations are probably due to the
suppression of high-voltage-activated calcium channels in the nerve terminals,
since, for example, ACh or prostaglandin E1 & E2 selectively suppressed both the
N- and R-type Ca2+ currents, through M2 muscarinic and EP3-receptors,
respectively in paratracheal ganglion cells. Parasympathetic nervous system also
releases nonadrenergic-noncholinergic (NANC) inhibitory neurotransmitters in
addition to ACh. The threshold level for ACh and NO release, for example, is
almost identical, thereby suggesting the possible interactions between NO and ACh
at the post-junctional cites, in addition to the prejunctional inhibitory action
of NO to suppress ACh release from the nerve terminal. In this context, NO
donors, including SNAP or Cys-NO, reduced the amplitude of carbachol-induced
Ca(2+)-dependent Cl- currents (I infinity h, I alpha(Ca)) dose-dependently (IC50:
about 10 microM) in the cat tracheal myocytes, and similar inhibition was also
exerted by dibutyryl cGMP (db-cGMP). However, two structurally distinct types of
G-kinase inhibitor, H-8 (2.5 microM) and KT5823 (1 microM) failed to counteract
the inhibitory effects of SNAP or db-cGMP. Another G-kinase-specific inhibitor,
(Rp)-8-pCPT-cGMPS, itself caused a marked reduction in I infinity h, thereby
indicating that inhibition of I infinity h by NO donors involves a cGMP-dependent
but G-kinase-independent mechanism. All these experimental facts taken together
indicate that there are pre- and post-junctional "brakings" in the excitatory
parasympathetic neuro-effector transmission. Furthermore, in the gastrointestinal
tract, Z-338, a newly synthetized gastroprokinetic agent, stimulates
gastrointestinal motility through inhibition of the pre-junctional braking system
through inhibition of M1 receptors. Such a drug may be useful to control the
respiratory and gastrointestinal smooth muscles.
PMID- 10190129
TI - [ATP-sensitive K+ channels of the cardiovascular system].
AB - ATP-sensitive K+ (KATP) channels are inhibited by intracellular ATP and activated
by intracellular nucleoside diphosphates, and thus provide a link between
cellular metabolism and excitability. They are widely distributed in various
tissues including heart and vasculature, and thus may play essential regulatory
roles in the cardiovascular system. Furthermore, KATP channels are the targets of
two important classes of drugs, i.e., the antidiabetic sulfonylureas which block
the channels, and a series of vasorelaxants called "K+ channel openers" which
tend to maintain the channels in an open conformation. Recently, the molecular
structure of KATP channels has been clarified in various tissues including
cardiovascular system to be a complex of at least two subunits, i.e. SUR and
Kir6.0. The KATP channels in heart and vascular smooth muscle now appear to be
the complexes of SUR2A/Kir6.2 and SUR2B/Kir6.1, respectively. Further works are
now in progress to understand the molecular mechanisms responsible for the
control of KATP channel function by intracellular nucleotides and drugs.
PMID- 10190130
TI - [Signal transduction through ATP receptors in brain and the development of new
drugs].
AB - The possible involvement of adenosine 5'-triphosphate (ATP) receptors in the
function of the hippocampus and of pain transmission is discussed. Involvement of
these receptors in the function of the hippocampus has been suggested by several
reports. In the paper we presented the data that ATP inhibits the glutamate
release in cultured hippocampal neurons. This and the report revealing that ATP
protected against cell death by glutamate suggest that ATP may be playing a role
in the protection of the hippocampus from over-stimulation. Microglia cells are
activated by the stimulation of ATP and releases plasminogen which is well known
to promote the development of mesencephalic dopaminergic neurons and enhance
neurite outgrowth from explants of neocortical tissue. Therefore, ATP may have a
role in repairing the damaged neuronal networks as well as protection.
PMID- 10190131
TI - [Facilitatory actions of the cognitive enhancer nefiracetam on neuronal Ca2+
channels and nicotinic ACh receptors: their intracellular signal transduction
pathways].
AB - Nootropics are proposed to serve as cognition enhancers. The underlying
mechanism, however, is largely unknown. We have attempted to assess the
intracellular signal transduction pathways mediating the action of nefiracetam, a
nootropic agent, on neuronal Ca2+ channels and nicotinic ACh receptors. In NG108
15 cells, nefiracetam (1 microM) enhanced the activities of N/L-type Ca2+
channels without affecting T-type The nefiracetam action was mimicked by
dibutyryl cAMP (1 mM), or blocked by pertussis toxin (PTX), indicating that PTX
sensitive inhibitory G-proteins and cAMP-dependent pathways mediate the drug
action. Nefiracetam also exerted a dose-dependent biphasic effect on Torpedo
nicotinic acetylcholine (nACh) receptors expressed in Xenopus oocytes, in which
the drug induced a short-term depression of ACh-evoked currents at submicromolar
concentrations (0.01-0.1 microM) and a long-term enhancement of the currents at
micromolar concentrations (1-10 microM). The depression was caused by activation
of PTX-sensitive G-protein-regulated cAMP-dependent protein kinase (PKA) with
subsequent phosphorylation of the ACh receptors; in contrast, the enhancement was
caused by activation of Ca(2+)-dependent protein kinase C (PKC) and the ensuing
PKC phosphorylation of the receptors. It is concluded that nefiracetam interacts
with PKA and PKC pathways, which may explain a cellular mechanism for the action
of cognitive enhancers.
PMID- 10190132
TI - [The effect of NC-1900: its ameliorating effects on impairments of learning and
memory in the CA1 neurons and its intracellular signal transduction pathways].
AB - Effects of arginine vasopressin (AVP(1-9)) and its analogues on the glycine (Gly)
induced Cl- currents (IGly) were examined in acutely dissociated rat hippocampal
CA1 neurons using nystatin perforated and conventional whole-cell patch recording
modes under voltage-clamp conditions. The results suggest that the activation of
V1 receptor induces IP3 production which release Ca2+ from IP3-sensitive Ca2+
storage sites. The Ca2+ binds to CaM, resulting in the activation of Ca2+/CaM
sensitive adenylate cyclases. Consequently, the activation of PKA inhibits IGly.
The inhibitory actions of NC-1900 and its analogues on IGly might be involved in
their ameliorating effects on impairments of learning and memory in the CA1
neurons.
PMID- 10190133
TI - [Functional neuropharmacology in the human brain using positron emission
tomography: PET imaging of impaired cognitive performance induced by sedative
antihistamines].
AB - Antihistamines are the efficacious drugs to be used for the symptomatic relief of
allergic diseases. The safety issue of antihistamines is of central importance
because of their widespread use in current medical practice. Positron emission
tomography (PET) was used to better understand the pharmacological effects of
antihistamines on the central nervous system. The H1 receptor occupancy was
examined in young male volunteers with [11C]-doxepin after the oral or
intravenous administration of antihistamines. In other studies, the cognitive
performance was also measured tachistoscopically before and after taking
antihistamines. The H1 receptor occupancy in the human cortex caused by
antihistamines is significantly correlated with the reported values of incidence
of sleepiness in clinical trials, and the occupancy is well proportional to the
impaired cognitive performance. To understand the brain mechanism of
antihistamine-induced "sleepiness and impaired cognition", the regional cerebral
blood flow (rCBF) during the task was measured using 3D-PET and H2(15)O before
and after administration of d-chlorpheniramine. After its administration, the
rCBF was significantly decreased on the bilateral middle temporal gyrus, midbrain
and anterior cingulate. These findings suggest that H1 receptor blockade would be
affected on the activity of the attention and cognitive system in the brain.
PMID- 10190135
TI - [Superoxide anion radical selectively increases Ca2+ release from cardiac
sarcoplasmic reticulum through ryanodine receptor Ca2+ channel].
AB - Because the net Ca2+ uptake in the sarcoplasmic reticulum (SR) of cardiac muscle
is a result of the activity of Ca(2+)-ATPase and of the SR Ca(2+)-release
channel, an abnormal Ca2+ uptake may be the result of the dysfunction of either
or both structures. The site or sites of action for oxygen-derived free radicals
(OFR) damage are unknown, although previous studies on the SR have focused on
damage to the Ca2+ pump. Direct effects of OFR on SR Ca(2+)-release channels may
be important in understanding their potential contribution to myocardial
ischemia/reperfusion injury. We confirmed that superoxide anion radical (O2.-)
generated from hypoxanthine-xanthine oxidase reaction decreases calmodulin
content and increases 45Ca2+ efflux from the heavy fraction of canine cardiac SR
vesicles. Electron spin resonance study showed that hydroxyl radicals are
generated in addition to O2.- from hypoxanthine-xanthine oxidase reaction, and
data indicate that O2.- is responsible for the observed effect. Current
fluctuations through single Ca(2+)-release channels have been also monitored
after incorporation into planar phospholipid bilayers. We directly demonstrate
that activation of the channel by O2.- stimulates Ca2+ release from heavy SR
vesicles and suggest the importance of accessory proteins such as calmodulin in
modulating the effect of O2.-.
PMID- 10190134
TI - [Expression of angiotensin type-2 receptors in rat brain during the cell injury].
AB - The present study examined changes in angiotensin type-2(AT2) receptor mRNA level
after global brain ischemia or during glutamate neurotoxicity in cultured
cortical cells in rats. The AT2 mRNA level increased by three-fold in both the
cortex and hippocampus, which are known to be sensitive to ischemic injury, 3 hr
after ischemia. The day 10-14 cortical neurons were exposed to glutamate at a
toxic concentration of 100 microM for 15 min. AT2 receptor mRNA was then
increased 2-fold after exposure to glutamate, while the maximum increase was
observed in a dose-dependent manner 3 hr after glutamate stimulation. AT2
receptor binding also increased 3-12 hr after glutamate exposure. The increase in
the mRNA level was antagonized by N-nitro L-arginine methyl-ester, a nitric oxide
synthase inhibitor. The hemoglobin, a nitric oxide trap, also inhibited the
increase in the mRNA level. These results suggest that the increase in the mRNA
level is associated with the nitric oxide synthesis by glutamate exposure. The
viability of cortical cells after glutamate stimulation was partially restored by
the antisense oligonucleotide for the AT2 receptor. The present results thus
suggest the AT2 receptor may in some way be related to one of the processes in
cell injury.
PMID- 10190136
TI - [Long-term effects of growth-activating agents on smooth muscle contraction and
endothelial function in organ-cultured rabbit mesenteric artery].
AB - In the endothelium-denuded arteries cultured in the presence of FBS,
morphological (i.e. smooth muscle disorientation and increase in collagen fiber)
and phenotypic changes in smooth muscle were observed. Correlated with these
changes, contractile force induced by high concentration of KCl and
norepinephrine was significantly decreased. In addition, Ca-induced contraction
in the permeabilized muscle was also significantly reduced. The reduced
contractility in the FBS-treated arteries was partially recovered by the
treatment with L-NMMA. In the endothelium-intact arteries cultured in the
presence of FBS or PDGF, substance P and ionomycin-mediated, endothelium
dependent relaxation (EDR) was significantly decreased compared to the arteries
cultured in serum-free condition. In addition, amounts of NO production and total
recoverable eNOS mRNA was reduced in the FBS and PDGF-treated arteries. In these
arteries, however, cGMP-dependent relaxation in smooth muscle was not impaired.
These results suggest that long-term treatment of vascular tissue with growth
activating agents causes morphological or phenotypic changes nad up-regulation of
NO production in smooth muscle, resulting in a reduced contractility.
Furthermore, longterm treatment with these agents impairs NO-mediated EDR by
decreasing eNOS mRNA and NO production.
PMID- 10190137
TI - [Functional analysis of G protein-coupled receptor kinase (beta ARK1) by
intracellular immunization].
AB - G protein-coupled receptor kinases (GRKs) are believed to involve in
desensitization of the G protein-coupled receptors. So far, cDNAs of six GRKs
were cloned from several species including human and rat. However, it is unknown
whether single GRK phosphorylates various receptors and desensitizes them in the
cells. To determine whether GRK2 (also called beta ARK1) involves desensitization
of the beta 1-adrenergic receptor-mediated response in heart, we tried to apply
monoclonal antibody which could recognize only beta ARK1 and inhibit its
phosphorylating activity to the heart cells. Monoclonal antibody was obtained by
immunization of carboxyl terminus of beta ARK1 as fusion protein of glutathione-S
transferase (GST). The resulting monoclonal antibody specifically reacted with
beta ARK1, and inhibited the binding of purified beta gamma subunit to the
carboxyl terminus. Monoclonal antibody completely inhibited phosphorylation of
the m2 muscarinic acetylcholine receptor as well as phosphorylation of GST
intracellular third loop fusion protein of the m2 receptor. When monoclonal
antibody was applied to myocyte prepared from guinea pig heart, the
desensitization of the beta 1-adrenergic receptor was partially inhibited as
measured by Ca2+ channel activation. Thus intracellular application of monoclonal
antibody is promising approach to analyze function of GRKs.
PMID- 10190138
TI - [Role of superoxide generation and degradation system of mast cells in allergic
inflammation].
AB - Rat peritoneal mast cells are stimulated to generate superoxide anion (O2) by the
addition of compound 48/80 and A23187. Recently, we demonstrated by
immunohistochemical and Western blot analysis that the mast cells contained the
p47phox protein, which was one of cytosolic component of the NADPH oxidase
system. In the present study, it was demonstrated that the mast cells contained
the p47phox mRNA, much similar to that of mouse leukocyte. The permeabilized mast
cells were stimulated to generate O2- by the addition of Ca2+, phospholipase A2
(PLA2) and arachidonic acid. Our data suggest the following:(1) cytosolic PLA2
may be activated by the elevation of [Ca2+]i; (2) the conjugation of membrane
component with cytosolic component may be stimulated by the released arachidonic
acid. The mast cell granules contained superoxide dismutase (SOD)-like enzyme,
which degradated O2-, generated in xanthine-xanthinoxidase system. SOD-like
enzyme was released from the granules by the treatment with Ca2+ and trapped by
the treatment with heparin. In conclusion, our studies suggest that the disorder
of the degradation system of O2- may contribute to the development of allergic
inflammation.
PMID- 10190140
TI - [Amyloidogenic peptides such as beta-amyloid, amylin and calcitonin strongly
enhance the susceptibility of rat hippocampal neurons to excitatory amino acids
in vivo].
AB - We have previously shown that in vivo injection of beta-amyloid (beta 1-40, beta
25-35) with non-toxic amounts of ibotenic acid, an excitatory amino acid, causes
synergistic and drastic neuronal degeneration in rat hippocampus. It was,
however, yet not clear whether the neuronal degeneration in vivo was associated
with their primary amino acid sequences, their secondary beta-structure or their
activities to suppress MTT reduction activity in vitro. In addition to beta
amyloid, other amyloidogenic peptides such as human amylin or calcitonin are
known to deposit extracellularly in systemic and peripheral amyloidosis. In this
study, we measured the activity of amyloidogenic peptides (beta 1-40, human
amylin and calcitonin) to suppress cellular MTT reduction activity in vitro and
their synergistic neurodegeneration with ibotenic acid in vivo. All amyloidogenic
peptides, but not non-amyloidogenic peptides (beta 40-1, BSA), suppressed the MTT
reduction activity in HeLa cells and in the primary cultured neurons in vitro,
and also produced the synergistic neuronal cell loss in rat hippocampal region by
enhancing the toxicity of ibotenic acid in vivo. The deposits of amyloidogenic
peptides at the injection sites were thioflavin S fluorescence positive,
suggesting the fibrillary beta-structures. These results indicate that the
neurodegeneration in vivo by amyloidogenic peptides is strongly associated with
their fibrillary beta-structure and their activity to suppress MTT reduction
activity in vitro.
PMID- 10190141
TI - [Apoptosis in the repeated cerebral ischemia--behavioral & histochemical study].
AB - We have been reported that the repeated cerebral ischemia induced more severe
disruption of spatial cognition than single ischemia without any other motor
disturbance in 8-arm radial maze task in rats. And we have been clarified that it
is corresponding with 60% of selective cell injury of the CA1 pyramidal cells in
the hippocampus. Recently, characteristics of apoptosis such as internucleosomal
DNA fragmentation have been found in excitotoxic neuronal death. In the present
study, we investigated how necrosis and apoptosis following repeated ischemia
involve to the cell death. Repeated cerebral ischemia (10 min x 2, 1 hr interval)
induced significant disruption of spatial cognition not only 24 hrs but also 7
days after reperfusion. The decrease of H.E-positive neurons was found in the
hippocampus CA1 area and frontal cortex within 3 days after reperfusion, while an
DNA fragmentation and TUNNEL-positive neurons in the same areas were found
afterward. Furthermore repeated cerebral ischemia-induced disruption of spatial
cognition and apoptosis in the hippocampal CA1 area were inhibited by YM-90 K(15
mg/kg,i.p.), which is a selective AMPA/KA receptor antagonist, but not by MK-801.
These results suggested that the apoptotic cell death may be occurred via non
NMDA receptor mechanism in relatively late phase of the reperfusion period and it
may relate to the incidence of the disruption of spatial cognition in the rat.
PMID- 10190139
TI - [A molecular mechanism for supersensitization of adenylyl cyclase system in
cloned opioid receptor-transfected cells following sustained opioid treatment].
AB - Chronic opioid treatment has been shown to develop supersensitization of adenylyl
cyclase (AC) system or cAMP overshoot. In this study, we investigated the
molecular mechanism of supersensitization of AC system using CHO cells expressing
one of the cloned mu-, delta- and kappa-opioid receptors. In naive cells, acute
treatment with an opioid agonist, but not antagonist, suppressed forskolin
stimulated cAMP accumulation. In the cells sustainedly (4 hr) treated with the
agonist, the challenge by antagonist induced the cAMP overshoot over the naive
level (supersensitization of AC system), but had no effect on GTPase activity.
This supersensitization of AC system was not affected by pretreatment with
cycloheximide, a protein synthesis inhibitor, or various protein kinase
inhibitors (H7, H8, H89 and staurosporine). On the other hand, pretreatment with
pertussis toxin blocked both inhibition of AC activity by acute agonist treatment
and development of supersensitization of AC system. To examine an involvement of
the interaction between G protein and AC in the supersensitization of AC system,
we used CHO cells coexpressing the opioid receptor and some chimeric G alpha
proteins between G alpha i2 and G alpha q. The results revealed that a specific
region of G alpha i2, which is responsible for the interaction with AC, is
closely related to the supersensitization. In addition, the supersensitization of
AC system was induced by sustained muscarinic agonist treatment in CHO cells
expressing the cloned m2 or m4 muscarinic receptor, suggesting this phenomenon is
common to the members of the Gi-coupled receptor superfamily. In conclusion,
these findings suggest that the development of supersensitization of AC system is
attributed to a continuous inhibition of AC by G alpha i, but not to continuous
activations of the Gi-coupled receptor and G protein themselves.
PMID- 10190142
TI - [Is endogenously released DOPA itself an upstream factor for increase in
glutamate release and delayed neuronal cell death induced by transient ischemia
in rats?].
AB - DOPA itself is a neuromodulator in striata. In rat striata, DOPA by itself
released neuronal glutamate in slices and caused cell death via glutamate release
in cultured fetal neurons, suggesting involvement of DOPA in an upstream process
of mechanisms for in vivo neuronal cell death. We attempted to clarify whether or
not this idea is truly the case in conscious Wistar rats. Four vessels were
occluded for 10 min during microdialysis of striata. DOPA, dopamine and glutamate
in perfusates collected every 10 min were measured by HPLC-ECD and
spectrophotometer. Delayed neuronal cell death in striata and hippocampus was
evaluated 96 hr after ischemia. DOPA was indeed evoked with dopamine and
glutamate during and after ischemia, and peak increases by respective 6-, 210-
and 8-fold of a basal level were seen at the fraction immediately after ischemia.
Delayed neuronal cell death was slight to moderate in striata and severe in
hippocampus. Intrastriatal perfusion of NSD-1015, a central DOPA decarboxylase
inhibitor, at 30 microM 10 min before ischemia, markedly increased DOPA and
glutamate release by ischemia with slight inhibition of dopamine release and
exaggerated delayed neuronal cell death in striata. Meanwhile, intrastriatal
perfusion of DOPA cyclohexyl ester (DOPA CHE) at 10-100 nM, a novel stable potent
competitive DOPA antagonist, antagonized dose-dependently increases in glutamate
release by ischemia without modification of dopamine release. DOPA CHE at 100 nM
protected striatal neurons from delayed cell death. Hippocampal neuronal cell
death was neither affected by NSD-1015 nor by DOPA CHE. Endogenously released
DOPA itself seems to act on its recognition site and to be a causal factor for
increase in glutamate release and resultant delayed neuronal cell death by
transient ischemia in rats.
PMID- 10190144
TI - [Activation of astrocytes and ischemic damage following the transient focal
ischemia].
AB - Astrocytes play vital roles not only in the mechanical support of the central
nervous system but also in the metabolism of neurotransmitters and in the
transfer of nutritive substances to neuron. After ischemic brain injuries, it has
been known that gliosis appears around degenerative regions and repairs these
regions. Recently, accumulating evidence indicates that overexpression of S-100
protein, astrocyte-derived protein, is detrimental to neuronal cells in various
pathological conditions. To confirm the astrocytic activation in cerebral
ischemia, we examined immunohistochemical changes in S-100 protein and glial
fibrillary acidic protein (GFAP) in the transient focal ischemia. Cerebral
infarction determined by hematoxylin-eosin staining was slight on day 1 and
further expanded on day 2 and 3. Thereafter, GFAP immunoreactivity was observed
in boundary zone of the infarct area at 72 hours after the transient focal
ischemia. On the other hand, S-100 protein immunoreactivities were markedly
increased at 9 hours after the transient focal ischemia. After the infarct
formation, the increase of S-100 immunoreactivity was observed in outside
boundary of infarct area. These results suggest that astrocytic activation, which
we would like to be called "pre-mitotic S-100 peak (PSP)", precedes the
neurodegeneration following the transient focal ischemia, and should be
distinguished from so-called gliosis observed in the post-neurodegeneration and
GFAP-dependent astrocytic proliferation.
PMID- 10190143
TI - [Protective effect of neurotrophin against glutamate neurotoxicity in cortical
cultures].
AB - This study was performed to investigate the effects of neurotrophins on glutamate
cytotoxicity by using cultured cortical neurons. Primary cultures obtained from
the cerebral cortex of fetal rats (17-19 days gestation) were used for
experiments. NGF did not elicit tyrosine phosphorylation of Trks whereas BDNF
induced Trk tyrosine phosphorylation within 10 min, followed by time-dependent
decrease. Brief glutamate exposure to the cell induced delayed cytotoxicity.
Similar cytotoxicity was observed with the brief application of a calcium
ionophore, ionomycin, and nitric oxide (NO) generating agents, S-nitrosocysteine
(SNOC) and SIN-1. Exposure of the cultures to NGF and BDNF for 1 or 24 hr prior
to glutamate exposure reduced glutamate-induced cytotoxicity. In contrast,
simultaneous addition of NGF and BDNF with glutamate did not affect glutamate
induced cytotoxicity. Ionomycin-induced cytotoxicity was prevented by exposing
cultures to NGF and BDNF for 24-hr. Moreover, NGF and BDNF ameliorated
cytotoxicity induced by SNOC and SIN-1. These results suggest that neurotrophins
prevent NO mediated glutamate cytotoxicity.
PMID- 10190145
TI - [Role of ryanodine receptors in hydrogen peroxide-induced DNA fragmentation and
thymidine incorporation in cultured rat astrocytes].
AB - In the CNS, reactive oxygen species (ROS) have been implicated in a wide range of
degenerative processes including amyotrophic lateral sclerosis, ischemia
reperfusion injury, Alzheimer disease, Parkinson disease and aging. However, the
exact mechanism is unknown, and there is little information on possible roles of
ROS in cell injury and the process on recovery of astrocytes, the most abundant
glial cells in the brain. We examined hydrogen peroxide (H2O2)-induced DNA
fragmentation and thymidine incorporation into cultured astrocytes as an
indicator of the process of recovery from astrocytic DNA injury. Astrocytes were
isolated from cerebral cortices of 0-day-old rats and treated with 1 mM dibutyryl
cyclic AMP for 4 days. H2O2 of 100 microM stimulated thymidine incorporation into
astrocytes. Caffeine, ryanodine, cyclic ADP-ribose (endogenous ryanodine receptor
agonist) and beta-NAD+ (precursor of cyclic ADP-ribose) suppressed partially the
stimulatory effect of H2O2. Ruthenium red (ryanodine receptor antagonist)
facilitated further the stimulatory effect of H2O2. The facilitated effect of
ruthenium red on H2O2-induced thymidine incorporation was suppressed by caffeine,
ryanodine, cyclic ADP-ribose and beta-NAD+. H2O2-induced DNA fragmentation and
astrocytic death were suppressed by ruthenium red. These findings suggest that
the process of recovery from astrocytic DNA injury by H2O2 may be regulated by
Ca2+ efflux from ryanodine-sensitive intracellular Ca2+ stores.
PMID- 10190146
TI - [Thromboxane A2 receptor-mediated signal transduction in glial cells].
AB - Thromboxane A2 (TXA2) receptor subtypes and their signal transduction were
examined in 1321N1 human astrocytoma cells. Placental and endothelial types of
TXA2 receptor mRNA were found in astrocytoma cells by RT-PCR procedure. Using
immunoaffinity column conjugated with anti-TXA2 receptor antibody, two TXA2
receptors (58 and 55 kDa) were partially purified. The partially purified TXA2
receptor fraction contained Gq/11 and G12. The incubation of the cells with
dibutyryl cyclic AMP (dbcAMP) caused a differentiation of human astrocytoma
cells. DbcAMP treatment resulted in the reduction of Ca2+ elevation and
phosphoinositide hydrolysis induced by TXA2 receptor agonist. Whereas the
responsiveness of Ca2+ signaling was weakened by dbcAMP treatment,
phosphorylation of mitogen-activated protein kinase was increased in dbcAMP
treated cells. These results suggested that human astrocytoma cells express
placental and endothelial TXA2 receptors. The TXA2 receptors were coupled with
Gq/11 and G12. DbcAMP treatment discriminates TXA2 receptor-mediated MAPK
activation from the Ca2+ signaling pathway.
PMID- 10190147
TI - [Possible involvement of caspase activation in nitric oxide-induced neuronal
apoptosis in SH-SY5Y cells].
AB - We here report involvement of caspases in NO-induced neuronal apoptosis. Our
experiments were designed to elucidate how NO induces neuronal cell death using
NOC18, a new type of NO donor that spontaneously releases NO alone, without
enzymatic metabolization. NOC18 induced apoptosis in human neuroblastoma SH-SY5Y
cells in a concentration- and time-dependent manner estimated with DNA
fragmentation assay, FACScan analysis, and nuclear morphology. In this study,
oxyhemoglobin, an NO trapper, suppressed NOC18-triggered DNA fragmentation,
indicating that NO from NOC18 is an apoptosis-inducer. An increase in caspase-3
like protease activity was observed in parallel with the induction of apoptosis,
but no caspase-1-like protease activity was detected. The level of pro-caspase-2
protein, a precursor of caspase-2, was decreased dramatically. In addition, NOC18
also caused the cleavage of PARP, yielding an 85 kDa protein, a typical fragment
of the caspases reaction. Oxyhemoglobin blocked the decrease in pro-caspase-2 and
the cleavage of PARP by NOC18. Moreover, NO elicited the release of cytochrome c
into the cytosol from mitochondria during apoptosis. These results suggest that
activation of caspases by cytochrome c released from mitochondria is involved in
neuronal apoptosis induced by NO.
PMID- 10190148
TI - [Influence of nitric oxide synthetase inhibitor on the blood pressure action of
clonidine in rats].
AB - We are investigating the influence of NO synthetase inhibitor on the clonidine
induced cardiovascular actions in urethane-anesthetized rats. The systemic blood
pressure was measured from right femoral artery, heart rate from the pressure
pulse under inhalation of O2. Nw-nitro-L-arginine-methylester (L-NAME, 5 mg/kg),
NO synthetase inhibitor, administered intravenously increased blood pressure
slightly, although decreased heart rate. The responses to L-NAME were stable
about 10 min after the injection. Clonidine (5 mg/kg) administered intravenously
indicated the transient increase blood pressure and following continuous decrease
of blood pressure. The early transient hypertension of clonidine was potentiated
by pretreatment with L-NAME and later continuous hypotension was markedly
inhibited. While, the early transient hypertension of clonidine was inhibited by
pretreatment with L-arginine and later continuous hypotension was potentiated.
The hypertension and tachycardia of intravenous tyramine was enhanced by L-NAME.
Clonidine administered into the cerebroventricle did not indicate the early
transient hypertension, though produced the later continuous hypotension. These
results suggest that L-NAME modifies the cardiovascular responses to clonidine
and NO may participate in the modulation.
PMID- 10190149
TI - [The involvement of muscarinic M1 receptor in the regulation of action potentials
in mouse isolated right atria].
AB - We investigated the involvement of muscarinic M1 receptors in the regulation of
action potentials, and its modulation by adrenergic signaling and its change by
aging in mouse isolated right atria using a conventional glass microelectrode
technique. In adult mice, acetylcholine (ACh) (3-10 microM) reduced the maximum
upstroke velocity of action potential (Vmax) followed by an increase. In
electrically driven atria, similar effects of ACh on Vmax were observed. McN-A
343 (100-300 microM), a M1 agonist, reduced Vmax, while M2 agonist oxotremorine
(0.1-0.3 microM), increased it. Isoproterenol (3 nM), antagonized ACh- and McN-A
343-induced reduction of Vmax, and potentiated the ACh- and oxotremorine-induced
increase. The effects of isoproterenol were mimicked by cholera toxin, a Gs
protein activator, and forskolin, a direct activator of adenylyl cyclase. H-89, a
selective protein kinase-A inhibitor, abolished the antagonism by isoproterenol
of ACh-induced reduction in Vmax. Calphostin C, a selective protein kinase-C
inhibitor, but not pertussis toxin attenuated ACh-induced reduction in Vmax.
These results show that 1) ACh-induced reduction of Vmax and its subsequent
increase are mediated by the activation of muscarinic M1 and M2 receptors,
respectively, 2) the M1 and M2 subtypes may exert a balancing action on each
other, and 3) the beta-adrenergic activation antagonizes M1-mediated effects, and
enhances M2-mediated effects, on Vmax. In young mice, ACh (5-10 microM) increased
Vmax, which was abolished by AF-DX 116 (0.3 microM), a M2 antagonist. In aged
mice, ACh did not affect Vmax up to a concentration of 10 microM. The present
findings may be of importance in the occurrence of cardiac disfunction in aging.
PMID- 10190150
TI - [Signal transduction of serotonin release from enterochromaffin cells in mouse
ileal crypts].
AB - Although serotonin (5-HT) release from enterochromaffin (EC) cells is considered
to be regulated by multiple receptor-mediated mechanisms, little is known about
the signal transduction in EC cells. We investigated the effects of adrenoceptor
stimulation on 5-HT release from ileal tissue and intracellular calcium dynamics
of epithelial cells in isolated ileal crypts in mice. Ileal tissues placed in
organ bath were perfused with a buffered solution. Released 5-HT was measured
using HPLC-ECD. Ileal crypts were isolated by collagenase digestion followed by
moderate pipetting. Intracellular calcium dynamics were analyzed by digital video
imaging system using fura-2. NE, but not isoprenaline (Iso), induced 5-HT release
from mouse ileal tissue. NE-induced 5-HT release was antagonized by yohimbine and
rauwolscine, but not by prazosin and bunazosin. NE, but not Iso, also elicited a
transient elevation of intracellular calcium in some EC cells. The effect of NE
(1 microM) was slightly suppressed by prazosin and bunazosin, but was remarkably
suppressed by yohimbine and rauwolscine. UK 14,304 and Clonidine at 10 microM
significantly induced an increase in intracellular calcium concentration. NE
induced intracellular calcium dynamics was not significantly affected by timolol,
Ro20-1724, rolipram and 8-bromo-cAMP. These results suggest that NE-induced 5-HT
release from ileal EC cells is mediated predominantly via alpha 2-, but not beta
adrenoceptors, by a mechanism dependent on elevation of intracellular calcium
concentration.
PMID- 10190151
TI - [Anti-migraine effects of lomerizine].
AB - Lomerizine, a novel Ca2+ channel blocker, is under development as an anti
migraine drug. We examined the effects on spreading depression (SD) induced by a
brief period of hypoxia (40 to 60 sec) in rat hippocampal slices, the cortical
hypoperfusion and cortical c-Fos-like immunoreactivity that follow KCl-induced SD
in anesthetized rats as compared with those of flunarizine. Extracellular
recording was made from the CA1 subfield. The latency of initiated SD was
examined. Lomerizine (1 and 10 nM) and flunarizine (1 microM) significantly
prolonged the latency in a concentration-dependent manner. After KCl application
to the cortex, cerebral blood flow monitored by the laser Doppler flowmetry was
approximately 20 to 30% below baseline for at least 60 min. Lomerizine (0.3 and 1
mg/kg, i.v.) and flunarizine (1 and 3 mg/kg, i.v.) administered 5 min before KCl
application inhibited the cortical hypoperfusion that followed KCl application. c
Fos-like immunoreactivity, an indicator of neuronal activation, was detected in
the ipsilateral, but not in the contralateral frontoparietal cortex 2 hr after
KCl application. Lomerizine (3-30 mg/kg, p.o.) and flunarizine (30 mg/kg, p.o.)
significantly attenuated the expression of c-Fos-like immunoreactivity in the
ipsilateral frontoparietal cortex. Lomerizine was 3 to 1000 times more potent
than flunarizine in the above SD models. These findings suggest that the
inhibitory effects of lomerizine and flunarizine on the interval between the
initiated and subsequent spontaneous SDs, the cortical hypoperfusion and
expression of c-Fos-like immunoreactivity induced by SD are mediated via the
effects of Ca2+ entry blockade, which may include an increase in cerebral blood
flow and the prevention of excessive Ca2+ influx into brain cells.
PMID- 10190152
TI - [Identification of protein kinase C phosphorylation sites involved in
desensitization of the histamine H1 receptor].
AB - We studied whether direct phosphorylation plays a key role in protein kinase C
activating phorbol ester-mediated H1 receptor desensitization. Several potential
protein kinase C-mediated phosphorylation sites were located in the third
cytoplasmic loop form our cloning studies of H1 receptors. Ser396 and Ser398 were
determined to be the phosphorylation sites by in vitro phosphorylation studies
using synthetic peptides corresponding to the partial amino acid sequence of the
third cytoplasmic loop. Mutant H1 receptors whose Ser396 or Ser398 were displaced
by alanine were expressed in Chinese hamster ovary cells by site-directed
mutagenesis. Characterization of these receptors revealed that Ser398, but not
Ser396, was primarily responsible for protein kinase C-mediated H1 receptor
desensitization.
PMID- 10190153
TI - [Effects of arginine-vasopressin on neuronal interaction from the area postrema
to the nucleus tractus solitarii in rat brain slices].
AB - The effects of vasopressin (AVP) on area postrema (AP) neurons and the neuronal
connection between the AP and nucleus tractus solitarii (NTS) were investigated
electrophysiologically in slices preparation of the medulla oblongata of rats. In
the AP, 27.9% of 129 neurons were excited by AVP and 20.5% were inhibited. The
excitation was blocked by a V1 receptor antagonist. Synaptic transmission of the
AP to the NTS was mainly mediated by non-NMDA receptors. Local application of AVP
to the AP activated the NTS neurons. This activation was blocked by an NMDA
antagonist. These results suggest that the excitation originating in the AP is
conveyed to the NTS via non-NMDA receptors and modified by NMDA receptor
activation secondly. These processes may be important in regulation of the
arterial baroreceptor reflex.
PMID- 10190155
TI - [Cerebral revascularization surgery for moyamoya disease].
PMID- 10190156
TI - [Transnasal microsurgery using a micro-pressure-suction-irrigation system for
pituitary adenomas].
AB - Micro-pressure-suction-irrigation system (MPSIS), introduced by Luedecke et al,
is an instrumentation for the direct transnasal pituitary procedure. We improved
this system for use in Japan. The irrigation system can effectively clean the
operating field by one-hand manipulation and dissect tumor tissue by its rapid
flow. The pressure of suction and irrigation can be adjusted respectively by a
device in the handpiece. The MPSIS is applicable to different stages of
intervention because it is equipped with separate tips of various diameters,
lengths and angles. This system is especially useful in combination with a
micromirror or an endoscopy for direct inspection of the eccentric tumor sites
such as the cavernous sinus, the upper part of the planum sphenoidale, or the
posterior suprasellar regions. The use of the MPSIS helps to avoid injury to
normal tissue structures, and prevents tiny soft microadenoma from being lost
during preparation. We have proved the suitability and usefulness of the MPSIS in
23 surgical interventions for transnasal microsurgery of pituitary adenomas.
PMID- 10190157
TI - [A case of cerebellar hematoma due to venous angioma presenting trigeminal
dysfunction].
AB - With regard to the natural history of venous angioma, the risk of hemorrhage is
reported to be relatively higher if the lesion exists in the posterior fossa.
However a recent report of 100 cases of venous angioma concluded that the risk of
hemorrhage was low, being only 0.22%/year. Although the true rate of hemorrhage
is uncertain, we have encountered case of cerebellar hematoma due to venous
angioma in the posterior fossa where the patient presented with trigeminal
dysfunction and cerebellar ataxia, without any history of hypertension. We
considered that venous angioma in the posterior fossa might cause cerebellar
hemorrhage. After removal of the hematoma, the patient's symptoms were resolved.
In the posterior fossa, a relatively higher volume of venous blood would cause
venous congestion to occur more easily, leading to damage of the fragile wall of
the angioma.
PMID- 10190158
TI - [Cranio-cervical junction dural arteriovenous malformation presenting with
subarachnoid hemorrhage: report of two cases].
AB - Most spinal dural arteriovenous malformations (AVMs) affect the thoracic and
lumbar regions. The clinical features of dural AVMs are, usually, gradually
progressing myelopathy, while hemorrhage is a rare occurrence. We have recently
encountered two cases of cranio-cervical junction dural AVM which caused
subarachnoid hemorrhage. Both patients, a 61-year-old and a 37-year-old man were
admitted to our hospital due to sudden onset of severe headache. Left vertebral
angiography demonstrated a dural AVM at the cranio-cervical junction. A left
suboccipital craniotomy and left hemilaminectomy of the atlas were performed.
Dural opening disclosed tortuous dilated abnormal vessels. The dural AVM was fed
by multiple small dural branches of the left vertebral artery and drained into an
intracranial pial vein. The dura where the left vertebral artery penetrated was
coagulated and divided from the left vertebral artery. Postoperative courses of
these patients were uneventful. The pathophysiology and surgical treatment of
dural AVMs in the cranio-cervical junction are discussed.
PMID- 10190159
TI - [Intracranial primitive neuroectodermal tumor in an infant: a case report].
AB - A 2-month-old girl with a supratentorial primitive neuroectodermal tumor (PNET),
which extended into the skull, is herein presented. The patient underwent total
removal of the tumor and also received a course of postoperative chemotherapy.
After a follow-up period of 12 months, the infant is alive without recurrence.
Histologically, the tumor was composed of poorly differentiated neuroectodermal
cells, and these neoplastic cells showed a mild immunohistochemical reaction for
GFAP and synaptophysin, and a moderate reactivity for neuron specific enolase and
vimentin. In addition, a moderate level of immunoreactivity for HBA71 antigen
(p30/32M1C2), which is the product of the M1C2 gene and is found in peripheral
PNETs but not in central PNETs, was noted in many neoplastic cells. Although this
tumor was located intracranially, it may be classified as a peripheral PNET.
PMID- 10190160
TI - [Transient cortical blindness and convulsion mimicking a hemorrhagic complication
during embolization of the cerebellar AVM].
AB - We report a case of transient cortical blindness and convulsions during
embolization of the cerebellar AVM. A 29-year-old man was admitted to our
hospital with subarachnoid hemorrhage. Cerebral angiography showed the right
cerebellar AVM fed by the right superior cerebellar artery. Preoperative
embolization of the AVM was performed. During embolization, the patient lost
consciousness suddenly and appeared to be in a decerebrate posture. About 15
minutes later, the patient came around and complained of total blindness.
Cerebral angiography revealed the disappearance of the aneurysm and AVM. There
were no abnormal findings in the vertebrobasilar system. Computed tomography
obtained just after the procedure, showed considerable contrast enhancement of
the occipital lobes. Two hours later, a repeat computed tomography showed
clearance of contrast enhancement. Magnetic resonance imaging obtained 12 hours
after the procedure, showed no evidence of infarction in the occipital lobes. Two
days after, the patient's sight gradually returned. Seven days after the
procedure, the patient recovered completely. We speculated that these clinical
features might be convulsions due to contrast material. In the reported cases,
convulsions and transient cortical blindness due to non-ionic low osmolar
contrast materials is a rare complication. This case suggested disruption of the
blood-brain barrier demonstrated by the computed tomography appearance of
contrast enhancement in the occipital lobes.
PMID- 10190161
TI - [A case of unruptured cerebral aneurysm treated by intra-aneurysmal embolization
during outpatient hemodialysis for chronic renal failure].
AB - A 70-year-old woman, who had been receiving hemodialysis in a local hospital
every other day for 2 years, complained of occasional headaches. Magnetic
resonance imaging showed a large middle cerebral artery (MCA) aneurysm.
Angiography in the midterm day of hemodialysis demonstrated a large aneurysm on
the right MCA bifurcation. Her chronic renal failure made us hesitate to perform
craniotomy. Intra-aneurysmal Guglielmi detachable coil (GDC) embolization was
performed also in the midterm day of hemodialysis. She was admitted to our
hospital after hemodialysis on the day before the embolization. The embolization
was carried out under local anesthesia and systemic heparinization. The aneurysm
was almost completely embolized with five GDCs. She was transferred to the local
hospital to receive the next hemodialysis on the day after the embolization.
Patients with chronic renal failure are not suitable for neurosurgical therapy
because mortality of patients undergoing dialysis is 45-80%, which is mainly due
to disequilibrium syndrome and a hemorrhagic tendency. We propose that some cases
like this case should be treated with an intra-vascular neurosurgical technique.
In conclusion, this report demonstrates that intra-aneurysmal embolization is
less invasive and is a more suitable treatment for patients who are considered to
be at high risk for surgery and general anesthesia.
PMID- 10190162
TI - [A case of recurrent-rupture dermoid cyst].
AB - A 58-year-old man was seen because of general convulsions. The neurological
findings were normal at his first visit, but CT revealed a low density mass in
the right hypothalamus with calcification. T1-weighted image revealed multiple
high intensity lesions in the subarachnoid space. Only anti-epileptic drugs were
prescribed. He was readmitted one year later because of a traffic accident due to
convulsions. CT and MRI revealed other new lesions in the bilateral anterior
horn. After four uneventful years, follow-up CT revealed a dilation of the third
ventricle. MRI using the fat suppression method showed enhancement around the
main tumor and the wall of the lateral ventricles and stenosis of the aqueduct.
Right frontotemporal craniotomy was performed. Thickening of the arachnoids and
floating lipid droplets were seen in the sub-arachnoid space. A yellowish tumor
was found in the suprasellar region, adhering to the internal carotid artery. The
tumor contained soft yellowish tissue and hair. Only partial removal was carried
out because of severe adhesion to perforators. The lamina terminalis was opened
after tumor removal. The postoperative course was uneventful except for transient
diabetes insipidus.
PMID- 10190163
TI - [Extraneural metastasis of pineal germinoma through a ventriculoperitoneal shunt,
following histological change].
AB - Primary germinoma of the central nervous system carries a good prognosis because
of their radiosensitivity. Recurrence is rare and extraneural metastases are even
more unusual. We report a unique case of a primary intracranial germinoma
exhibiting complete response to radiotherapy, but recurring as an intra-abdominal
yolk sac tumor. The presence of a VP shunt is thought to have facilitated
metastatic spread of the intracranial neoplasm. An 21-year-old (corrected) male
was admitted with headache and consciousness disturbance. Computed tomography
(CT) revealed an enhanced tumor of the pineal region and hydrocephalus. A
ventriculo-peritoneal shunt was emplaced immediately. No serum tumor markers such
as alpha-fetoprotein or human chorionic gonadotropin were detectable. A test dose
of radiotherapy (whole brain 20Gy) was given. The tumor size was remarkably
decreased. Clinical diagnosis was germinoma. Additional whole brain radiation
(total 45Gy) and whole spine radiation (20Gy) were given. The tumor and the
hydrocephalus regressed completely and the patient returned to school. Three
years later, he experienced a feeling of abdominal fullness. CT and
echotomography of the abdomen showed a large peritoneal and intra-hepatic tumor.
But MRI revealed no recurrent tumor of the pineal lesion or of the other areas in
the central nervous system. Radiological and clinical findings showed no tumors
in the testis, the retroperitoneal cavity, or the thymus. Laboratory
investigation demonstrated elevated serum AFP (26,550 ng/ml). AFP level regressed
after combined chemotherapy. However, the patient died due to pneumonia and
multiple organ failure. Only needle necropsy was performed. The microscopic
appearance of the peritoneal tumor was confirmed to be an endodermal sinus tumor.
It was suspected to be a metastasis of the pineal tumor through the V-P shunt
system.
PMID- 10190164
TI - [Fibrous dysplasia of the skull presenting interesting neuroradiological
findings].
AB - A case of fibrous dysplasia of the frontal bone in a 51 year-old male is
described. He was admitted to our hospital with a hard, painless growing mass in
the left frontal region. A symmetrical protrusion of his forehead has been
observed since several years before. Neurological examination and laboratory data
revealed no abnormalities. Skull x-rays demonstrated two different lesions. One
showed a ground glass appearance in the supraorbital region, and the other showed
a radiolucent lesion with marginal sclerosis crossing the left coronal suture CT
scan revealed an intradiploic multilocular mass. T1 and T2 MR images showed an
abnormal low-intensity mass, and heterogeneous gadolinium-enhancement was noticed
in both lesions. Selective external carotid angiography showed tumor stain in the
left coronal mass fed by middle meningeal and superficial temporal arteries
mimicking intraosseous meningioma. On the other hand, a supraorbital hyperostotic
lesion showed no apparent vascularity. An operation was performed on the left
coronal lesion to verify the nature of the progressively enlarging mass, which
was histologically confirmed to be a fibrous dysplasia rich in numerous vessels.
Postoperative course was uneventful. Correlation with clinical activity and
enhancement pattern was not known, however, careful observation is required in
hypervascular fibrous dysplasia such as was observed in this case.
PMID- 10190165
TI - [Medulloblastoma originating in the pons].
AB - Medulloblastoma usually originates in the cerebellum. We report here a case of
medulloblastoma originating in the pons. Pontine medulloblastoma is extremely
rare, with only one report in the literature. An 11-year-old girl was admitted to
our hospital with vertigo. Magnetic resonance imaging (MRI) revealed a tumor
originating in the pons. On the 4th day after admission, the tumor bled. Because
the patient's life was in danger from brain herniation, hematoma removal and
tumor resection were carried out. The diagnosis was medulloblastoma. After
surgery, the patient received radiation therapy and chemotherapy. Unlike tumors
originating in the cerebellum, this tumor did not seem to be effectively reduced
by these therapies. Radiation therapy and chemotherapy may not be effective for
medulloblastoma originating in the pons. We considered it necessary to make a
histological diagnosis even though the tumor originated in the pons and resection
was difficult technically.
PMID- 10190166
TI - [Why is "brain" expressed as "brain"].
PMID- 10190167
TI - Comparative sequence analysis of 5.8S rRNA genes and internal transcribed spacer
(ITS) regions of trichomonadid protozoa.
AB - The taxonomic situation in the genus Tritrichomonas is the subject of
controversial discussion: potentially T. foetus and T. suis, the tritrichomonads
from cattle and swine, respectively, could belong to the same species. In order
to shed some light on this question, a molecular biological analysis was
performed. The 5.8S rRNA gene and the flanking internal transcribed spacer
regions (ITS1 and ITS2) of 12 different isolates of 3 Tritrichomonas species T.
foetus, T. suis and T. mobilensis were enzymatically amplified by PCR and
subcloned. Also, the corresponding regions of the trichomonads Trichomonas
vaginalis, T. tenax, T. gallinae and Pentatrichomonas hominis were included in
this study. Sequence analysis of cloned fragments was used to compare the
parasite isolates. The genus Tritrichomonas exhibited an extremely high degree of
homogeneity. All T. foetus and T. suis isolates had identical sequences, and only
1 substitution was found in the ITS2 region of T. mobilensis. In contrast, the
genus Trichomonas shared more diversity. The results obtained in this study
support a possible future revision of the taxonomic classification of
tritrichomonads.
PMID- 10190168
TI - Mixed-genotype infections of the rodent malaria Plasmodium chabaudi are more
infectious to mosquitoes than single-genotype infections.
AB - Interactions between parasite genotypes sharing a host are poorly understood, but
have important consequences for the epidemiology and evolution of the parasite.
In mixed-genotype malaria infections, patterns of asexual replication and
transmission favoured by natural selection may be different from those in single
genotype infections. The infectivity to mosquitoes of mixed-genotype and single
genotype infections were compared using 2 clones of Plasmodium chabaudi
inoculated into mice either together or alone. Mice given mixed-clone infections
received the sum of the inocula given to the single-clone controls. Mosquitoes
were fed on the mice and the numbers of oocysts which developed were counted to
assess transmission intensity. For 3 combinations of starting inocula and feed
days, mixed-clone infections produced more oocysts per mosquito than the sum of
the 2 single-clone infections. This effect was correlated with an increase in
gametocyte density, but was less clearly related to asexual infection parameters.
The results show that interactions between clones in mixed-clone infections can
profoundly affect transmission.
PMID- 10190169
TI - A model for the origins and spread of drug-resistant malaria.
AB - A general method of investigating parasite population genetics is presented and
used to investigate the evolution of drug resistance in Plasmodium. The most
important biological factor is the nature of the control, presumably through host
immunity, of the malarial infection. Two models are examined: a 'generalized
immunity' (GI) model in which immunity regulates the overall level of infection,
and a 'specific immunity' (SI) model in which each clone within the infection is
regulated independently. These models are used to investigate 3 critical factors
in the evolution of resistance: (i) the frequency of resistant alleles in the
population prior to drug use, (ii) the dynamics of resistance following drug
application and (iii) the magnitude of threshold frequencies below which
resistance will not evolve. These analyses also identify the implicit assumptions
made in several previous models, reconcile their differing conclusions and allow
a more informed debate about the practical application of drugs.
PMID- 10190170
TI - The epidemiology of canine leishmaniasis: transmission rates estimated from a
cohort study in Amazonian Brazil.
AB - We estimate the incidence rate, serological conversion rate and basic case
reproduction number (R0) of Leishmania infantum from a cohort study of 126
domestic dogs exposed to natural infection rates over 2 years on Marajo Island,
Para State, Brazil. The analysis includes new methods for (1) determining the
number of seropositives in cross-sectional serological data, (2) identifying
seroconversions in longitudinal studies, based on both the number of antibody
units and their rate of change through time, (3) estimating incidence and
serological pre-patent periods and (4) calculating R0 for a potentially fatal,
vector-borne disease under seasonal transmission. Longitudinal and cross
sectional serological (ELISA) analyses gave similar estimates of the proportion
of dogs positive. However, longitudinal analysis allowed the calculation of pre
patent periods, and hence the more accurate estimation of incidence: an infection
conversion model fitted by maximum likelihood to serological data yielded
seasonally varying per capita incidence rates with a mean of 8.66 x 10(-3)/day
(mean time to infection 115 days, 95% C.L. 107-126 days), and a median pre-patent
period of 94 (95% C.L. 82-111) days. These results were used in conjunction with
theory and dog demographic data to estimate the basic reproduction number, R0, as
5.9 (95% C.L. 4.4-7.4). R0 is a determinant of the scale of the leishmaniasis
control problem, and we comment on the options for control.
PMID- 10190171
TI - Cellular distribution of a feminizing microsporidian parasite: a strategy for
transovarial transmission.
AB - The cellular distribution of a vertically transmitted, feminizing microsporidian
was followed in its host Gammarus duebeni. In adult females the parasite was
restricted to gonadal tissue, in particular primary and secondary follicle cells.
Spores were diplokaryotic with a thin spore wall and a short polar filament,
characteristics typical of 'early' spores involved in autoinfection. The
diplokaryotic life-cycle, absence of spore groupings and of a pansporoblast
membrane typify the genus Nosema. However, the unusual globular polaroplast of
the spore and restriction of this stage to host ovarian tissue have not
previously been described in Nosema. Sporogony occurred only in follicle cells
adjacent to developing oocytes and was in synchrony with the process of
vitellogenesis. Oocytes were infected after formation of intracellular
connections with follicle cells but harboured only vegetative stages of the
parasite. Parasites were associated with the perinuclear cytoplasm and, in
developing embryos, segregated to daughter cells along the axis of the spindle.
In juvenile animals there was no evidence of pathology linked with feminization
and the parasite was found at low density in cells under the cuticle. The
parasite is highly adapted to transovarial transmission with an efficient
mechanism of oocyte infection and no evidence of pathology.
PMID- 10190172
TI - 'Total evidence' refutes the inclusion of Perkinsus species in the phylum
Apicomplexa.
AB - The phylogenetic affinities of the oyster pathogen Perkinsus marinus were
investigated with morphology, 18S-like rDNA data and actin sequence data.
Morphological investigations revealed that Perkinsus species do not have a conoid
and that other criteria which have been used to place them in the Apicomplexa are
general to alveolates. When considered separately, 18S-like rDNA and actin data
sets each support a closer affinity for Perkinsus marinus with the
dinoflagellates. However, each of these separate analyses possess their own
biases and weaknesses. Use of the phylogenetic principle of 'total evidence' in
which data sets are combined in simultaneous analysis yielded a more robust
hypothesis that is stable both to character and taxonomic sampling. The resulting
cladogram strongly corroborates the placement of Perkinsus species with the
Dinoflagellida and not with the Apicomplexa.
PMID- 10190173
TI - Schistosoma mansoni sporocysts contain rhodoquinone and produce succinate by
fumarate reduction.
AB - Although schistosomes were thought to be one of the few parasitic helminths that
do not produce succinate via fumarate reduction, it was recently demonstrated
that sporocysts of Schistosoma mansoni produce, under certain conditions,
succinate in addition to lactate. This succinate production was only observed
when the respiratory chain activity of the sporocysts was inhibited, which
suggested that succinate is produced by fumarate reduction. In this report the
presence of essential components for fumarate reduction was investigated in
various stages of S. mansoni and it was shown that, in contrast to adults,
sporocysts contained a substantial amount of rhodoquinone which is essential for
efficient fumarate reduction in eukaryotes. This rhodoquinone was not made by
modification of ubiquinone obtained from the host, but was synthesized de novo.
Furthermore, it was shown that complex II of the electron-transport chain in
schistosomes has the kinetic properties of a dedicated fumarate reductase instead
of those of a succinate dehydrogenase. The presence of such an enzyme, together
with the substantial amounts of rhodoquinone, shows that in S. mansoni sporocysts
succinate is produced via fumarate reduction. Therefore, the energy metabolism of
schistosomes does not differ in principle from most other parasitic helminths,
which are known to rely heavily on fumarate reduction.
PMID- 10190174
TI - A vesicle preparation for resolving single-channel currents in tegument of male
Schistosoma mansoni.
AB - A tegumental vesicle preparation from adult male Schistosoma mansoni was
developed that allows the resolution of single ion-channel currents. Adult male
schistosomes were exposed to a low pH (3.75) medium for a period of approximately
30 min at 37 degrees C. During this period smooth vesicles formed from the
tegument. Fluorescence microscopy following staining of the tegument with the
dye, 5-N-[octadecanoyl]aminofluorescein (AF-18), transmission electron microscopy
and scanning electron microscopy revealed that the vesicles were produced from
the outer tegumental membrane. The fluorescence studies showed the presence of
the double bilayer structure of the outer membrane in > 41% of the vesicles.
These studies suggested that the preparation is suitable for single-channel
recording with the patch-clamp technique. Cell-attached and isolated inside-out
patch recordings of ion-channel activity were obtained with giga-ohm resistance
seals. Different types of ion-channel were recorded from tegumental vesicles from
male schistosomes, illustrating the potential of the technique. The channels
observed included: a non-selective cation channel (360 pS); a K+ channel (with a
conductance of 115 pS in high bath-K conditions); and a Cl- selective channel (20
pS). The currents of these ion-channels may cross the double bilayer of the outer
tegumental membrane.
PMID- 10190175
TI - The suppressive excretory-secretory product of Trichobilharzia ocellata: a
possible factor for determining compatibility in parasite-host interactions.
AB - Factors which may determine trematode-snail interactions were assessed in the
present study. Compatibility was examined using a bacterial clearance assay to
detect the modulatory effects of both compatible and incompatible trematode
infections on the activity of haemocytes from Lymnaea stagnalis, during the early
stages of infection. Exposure to and injection with Trichobilharzia ocellata, a
compatible trematode, or the incompatible Schistosoma mansoni, resulted in
modulation of haemocyte activity. However, T. ocellata activated haemocytes 1.5 h
post-infection (p.i.) and then suppressed activity 24-72 h p.i. whereas with S.
mansoni no suppression, only activation of haemocytes was observed throughout the
test period (1.5-72 h p.i.). In previous studies, modulation of the haemocyte
clearance activity by T. ocellata was found to be mediated by 2 E-S fractions, an
activating fraction and a suppressing one. Investigations to assess whether the
lack of suppression of haemocyte activity, observed in the S. mansoni-L.
stagnalis incompatible trematode-snail interaction studied, was due to either the
absence or ineffectiveness of the suppressing E-S fraction, were performed on a
second incompatible combination, T. ocellata-Planorbis corneus. Using this
combination it was revealed that only the activating E-S fraction had modulatory
effects on P. corneus haemocytes, indicating that the suppressing E-S fraction,
which actively interferes with the clearance activity of haemocytes from L.
stagnalis, appears to act in a host-specific manner. In conclusion, the
suppressing E-S fraction determines, at least in part, compatibility in the
trematode-snail association studied. This is also probably likely in other
trematode-snail combinations.
PMID- 10190176
TI - Myophilin of Echinococcus granulosus: isoforms and phosphorylation by protein
kinase C.
AB - Myophilin is a muscle-associated antigen of the taeniid cestode Echinococcus
granulosus. This protein shows a high amino acid sequence homology with calponins
and calponin-like proteins, which are proposed to be associated with the
regulation of smooth muscle contraction. In order to provide supportive evidence
for a relationship between these proteins, we characterized myophilin using
electrophoretic, biochemical and molecular biological approaches. Two-dimensional
protein electrophoretic separation of E. granulosus larval proteins defined 4
isoelectric isoforms of myophilin (alpha, beta, gamma and delta), which appeared
to be a consequence of post-translational modification of a single gene product.
It was also demonstrated biochemically that E. granulosus myophilin undergoes
specific phosphorylation in vitro by protein kinase C (PKC). Finally, myophilin
homologues were identified in extracts of Taenia hydatigena and T. ovis by
immunoblot. A partial cDNA of the closely related species, E. multilocularis, was
isolated by cloning procedures and showed 99% homology with the E. granulosus
myophilin gene. The similarities of E. granulosus myophilin with calponins in
their tissue localization, protein isoforms patterns, ability to be
phosphorylated in vitro by PKC, and the relatively conserved nature of the
protein among related parasites suggest that myophilin may be associated with
smooth muscle contraction.
PMID- 10190177
TI - The effects of the peptides AF3 (AVPGVLRFamide) and AF4 (GDVPGVLRFamide) on the
somatic muscle of the parasitic nematodes Ascaris suum and Ascaridia galli.
AB - AF3 (AVPGVLRFamide) and AF4 (GDVPGVLRFamide) are endogenous RFamide-like peptides
isolated from the parasitic nematode Ascaris suum. Here the actions of these
peptides on the somatic musculature of Ascaris have been investigated and
compared to the action of acetylcholine (ACh), the excitatory transmitter at the
neuromuscular junction. ACh, AF3 and AF4 contracted muscle with EC50S of 13 +/- 1
microM, 24 +/- 6 nM and 37 +/- 2 nM, respectively (n = 6). The muscle cells were
depolarized by ACh (3 microM; 5.2 +/- 0.4 mV, n = 42), AF3 (1 microM; 2.6 +/- 0.3
mV, n = 19) and AF4 (1 microM; 3.3 +/- 0.4 mV, n = 19). EC50S were 681 +/- 329 nM
(AF3) and 901 +/- 229 nM (AF4), but an estimate could not be made for ACh due to
muscle contraction at concentrations greater than 10 microM. The depolarization
to 3 microM ACh was abolished by the nicotinic receptor antagonist mecamylamine
(10 microM; n = 5) but the responses to the peptides were not (111 +/- 7% and 108
+/- 17% with respect to control; n = 5). The depolarization elicited by ACh was
reduced to a greater extent by a 50% reduction in extracellular Na+ concentration
than the response to AF3 and AF4 (P < 0.02). Cobalt was more effective at
blocking the AF3 and AF4 depolarizations than those to ACh. These observations
suggest that AF3 and AF4 contract Ascaris muscle without an action at the Ascaris
nicotinic receptor. Furthermore, the ionic mechanism through which AF3 and AF4
depolarize Ascaris muscle is different from that for ACh. ACh, AF3 and AF4 were
also found to contract Ascaridia galli somatic muscle with EC50S of 13 +/- 3
microM, 721 +/- 236 nM and 371 +/- 177 nM, respectively (n = 7). The muscle cells
were depolarized by ACh (EC50 = 14 +/- 5 microM, n = 5), AF3 (EC50 = 5 +/- 3
microM, n = 4) and AF4 (EC50 = 10 +/- 5 microM, n = 4). Therefore the response to
these peptides is not unique to Ascaris and they may subserve a functional role
in the motor nervous system of parasitic nematodes.
PMID- 10190178
TI - Hypoglycaemic activity of four plants used in Chilean popular medicine.
AB - The hypoglycaemic activity of a 20% dried leaf infusion of Bauhinia candicans
Benth. (Leguminosae), Galega officinalis L. (Leguminosae), Morus alba L.
(Moraceae) and Rubus ulmifolius Schott. (Rosaceae), used for diabetes in Chilean
popular medicine, was evaluated in alloxan and streptozotocin induced
hyperglycaemic rats. In normal rats the different infusions did not modify
significantly the glycaemia in the period studied, but in diabetic rats different
results were observed, depending on the diabetogenic drug used. B. candicans and
R. ulmifolius infusions elicited remarkable hypoglycaemic effects in both
experimental models. B. candicans presented a greater decrease of glycaemia in
alloxan diabetic rats (39%) and R. ulmifolius showed a similar activity in both
alloxan and streptozotocin diabetic rats (28% and 29%). Activity-guided
fractionation of R. ulmifolius showed that petroleum ether extracts elicited a
marked hypoglycaemic effect (35%) in the streptozotocin induced model.
PMID- 10190179
TI - Antihepatotoxic activity of Swertia chirata on paracetamol and galactosamine
induced hepatotoxicity in rats.
AB - The extracts of Swertia chirata were evaluated for antihepatotoxic activity using
paracetamol and galactosamine models. The methanol extract of the whole plant was
found active at a dose of 100 mg/kg i.p. On fractionating this extract into
chloroform soluble and butanol soluble fractions, the activity was retained in
the chloroform soluble fraction which was most active at a dose level of 25 mg/kg
i.p. with overall protection of 81% and 78% against paracetamol and
galactosamine, respectively. The butanol soluble fraction, rich in bitter
secoiridoids, was devoid of significant activity. The protective effect observed
against these two hepatotoxins which are different in their mechanisms of
inducing hepatotoxicity, suggests broader and non-specific protection of the
liver against these two toxins by non-bitter components of Swertia chirata.
PMID- 10190180
TI - Antiprotozoal properties of Helianthemum glomeratum.
AB - Structure characterization and biological evaluation of the compounds isolated
from Helianthemum glomeratum, particularly that of the polyphenols, has been the
aim of a series of studies carried out to define the further potential use of
this plant in the treatment of infectious diarrhoea in children. The flavan-3
ols, (-)-epigallocatechin and (-)-epigallocatechin gallate, isolated from
Helianthemum glomeratum roots were tested for their antiamoebic and antigiardial
effects in vitro. Compared with the activity determined with the leaf and the
root methanol extracts, the effect of (-)-epigallocatechin against Entamoeba
histolytica was of a similar potency, nevertheless, it also suppressed the growth
of Giardia lamblia in axenic cultures, a parasite that proved to be resistant to
the crude extracts. It might be assumed that determined biological properties are
due to the presence of (-)-epigallocatechin in the plant, although the
flavonoids, kaempferol and tiliroside isolated from the leaves, could account for
the antiprotozoal properties of this herbal resource, used in Mayan traditional
medicine for the treatment of bloody diarrhoea.
PMID- 10190181
TI - Effects of extracts of seed and leaf of Piper guineense on skeletal muscle
activity in rat and frog.
AB - The pharmacological effects of leaf and seed extracts of Piper guineense were
investigated on phrenic nerve hemidiaphragm activity following electrical
stimulation in vitro. The Leaf and seed extracts (10 micrograms-1 mg/mL) and (50
800 micrograms/mL) respectively produced biphasic effects consisting of an
initial enhancement followed by secondary transient or prolonged depression of
twitch tension in response to electrical stimulation of both muscle and nerve.
These effects were similar to that of decamethonium (2-800 mg/mL). An increased
concentration of extracellular Ca2+ in vitro reversed the twitch contraction
inhibited by the leaf and seed extracts in a dose related pattern following
electrical stimulation. It is concluded that the leaf and seed extracts of Piper
guineense possess among other pharmacological properties, a depolarizing
neuromuscular blocking action.
PMID- 10190182
TI - Modulatory potential of Spirulina fusiformis on carcinogen metabolizing enzymes
in Swiss albino mice.
AB - The modulatory potential of Spirulina fusiformis was observed on the hepatic and
extrahepatic carcinogen metabolizing enzymes in Swiss albino mice at a dose of
800 mg/kg b.w. given orally. A significant reduction in the hepatic cytochrome P
450 content was observed in the group treated with Spirulina in comparison with
the control group. The hepatic glutathione S-transferase activity was induced
significantly by Spirulina treatment. There was no change in the extrahepatic
glutathione S-transferase activity after the animals were fed with Spirulina.
PMID- 10190183
TI - In vitro and in vivo evaluation of betulinic acid as an antimalarial.
AB - The lupane-type triterpene betulinic acid was isolated from an ethanol extract of
the root bark of the Tanzanian tree Uapaca nitida Mull-Arg. (Euphorbiaceae). The
in vitro antiplasmodial IC50 values of betulinic acid against chloroquine
resistant (K1) and sensitive (T9-96) Plasmodium falciparum were found to be 19.6
micrograms/mL and 25.9 micrograms/mL, respectively. The in vitro activities of
several related triterpenes were also evaluated. Betulin was found to be inactive
at 500 micrograms/mL for both K1 and T9-96. Ursolic acid exhibited IC50 values of
36.5 micrograms/mL and 28 micrograms/mL, and oleanolic acid exhibited IC50 values
of 88.8 micrograms/mL and 70.6 micrograms/mL against K1 and T9-96, respectively.
When betulinic acid was tested for in vivo activity in a murine malaria model (P.
berghei) the top dosage employed of 250 mg/kg/day was ineffective at reducing
parasitaemia and exhibited some toxicity. Betulinic acid has not previously been
evaluated for in vivo activity. This is believed to be the first compound to be
isolated from U. nitida.
PMID- 10190184
TI - Effects of Corylus avellana in acetaminophen and CCl4 induced toxicosis.
AB - Our study investigated the effects of Corylus avellana extract on acetaminophen
and carbon tetrachloride intoxicated liver of young rats. Hepatocytolysis was
determined by measuring the level of serum transaminases (GPT and GOT), steatosis
by Sudan black staining, histological structures by hamatoxylineosin staining and
the activity of enzymes such as SDH, GtDH, G-6-Pase and ATPase. Comparatively,
the most serious lesions appeared in CCl4 intoxication. Corylus avellana extract
had some beneficial effects in CCl4 toxicosis: it reduced hepatocytolysis as well
as histological lesions and returned the activity of some enzymes to normal
values.
PMID- 10190185
TI - Antiinflammatory activity of some extracts from plants used in the traditional
medicine of north-African countries (II).
AB - Aqueous, ethanol and chloroform extracts from Corrigiliola telephiifolia,
Echinops spinosus, Kundmannia sicula, Tamarindus indica and Zygophyllum gaetulum
were evaluated for antiinflammatory properties in mice (ear oedema induced by
arachidonic acid) and rats (subplantar oedema induced by carrageenan) after
topical or i.p. administration, respectively. Our results showed that all the
plants exhibit antiinflammatory activity, since at least one extract from each
plant was active in one of the experimental models. Whereas all the extracts of
Corrigiliola telephiifolia and Echinops spinosus were highly active on all the
experimental models assayed (values of inflammation inhibition well above 50%),
poorer activity profiles were recorded in Kundmannia sicula, Tamarindus indica
and Zygophyllum gaetulum. These results support the traditional uses for these
plants but indicate that the active principles in the chloroform extracts are
probably more active and/or are contained in larger concentrations than the
principles in the polar extracts used in the traditional medicine of North
African countries.
PMID- 10190186
TI - The effect of maimendongtang on airway clearance and secretion.
AB - We investigated the effect of Maimendongtang on airway clearance and secretion in
anaesthetized quails. The oral application of 1 g/kg of Maimendongtang
significantly increased tracheal mucociliary transport velocity (MCTV), whereas
100 or 300 mg/kg of Maimendongtang failed to do so. Moreover, 300 mg/kg or 1 g/kg
of Maimendongtang markedly attenuated human neutrophil elastase (HNE) or DNA
induced decrease in MCTV although 100 mg/kg of Maimendongtang had little effect.
Furthermore, we found that Maimendongtang significantly restored HNE-induced
increases in DNA, fucose and protein contents of airway surface fluid (ASF),
whereas only Maimendongtang itself significantly decreased the protein content.
These results indicate that Maimendongtang increases MCTV and the increase may
be, at least in part, ascribed to the amelioration of ASF in the trachea.
PMID- 10190187
TI - Effects of shiitake (Lentinus edodes) extract on human neutrophils and the U937
monocytic cell line.
AB - The aqueous extract of the shiitake mushroom was found to decrease IL-1
production and apoptosis in human neutrophils, as measured by ELISA and flow
cytometry respectively. It was found to increase IL-1 production and apoptosis in
the U937 monocytic cell line. The extract showed no significant effects on the
superoxide production of both neutrophils and U937 cells, as measured by
chemiluminescence. The extract was further separated into high and low molecular
weight components, and it was found that the low molecular weight component
retained the activity of the whole extract. This further suggests that the active
substance is a novel compound distinct from lentinan, a well-studied high
molecular weight anti-tumour agent found in shiitake.
PMID- 10190188
TI - Effect of parsley (Petroselinum crispum) on the skin of STZ induced diabetic
rats.
AB - Parsley (Petroselinum crispum) is one of the medicinal herbs used by diabetics in
Turkey and it has been reported to reduce blood glucose. The purpose of this
study therefore was to investigate the effect of feeding parsley on diabetes
induced impairments in rat skins. Uncontrolled induced diabetes caused
significant increases in nonenzymatic glycosylation of skin proteins, lipid
peroxidation and blood glucose. Administration of parsley extract did not inhibit
these effects except for the increase in blood glucose. SDS-polyacrylamide gel
electrophoresis revealed no significant differences in any protein bands between
any of the groups.
PMID- 10190189
TI - Antiviral activity of some South American medicinal plants.
AB - Folk medicinal plants are potential sources of useful therapeutic compounds
including some with antiviral activities. Extracts prepared from 10 South
American medicinal plants (Baccharis trinervis, Baccharis teindalensis,
Eupatorium articulatum, Eupatorium glutinosum, Tagetes pusilla, Neurolaena
lobata, Conyza floribunda, Phytolacca bogotensis, Phytolacca rivinoides and
Heisteria acuminata) were screened for in vitro antiviral activity against herpes
simplex type I (HSV-1), vesicular stomatitis virus (VSV) and poliovirus type 1.
The most potent inhibition was observed with an aqueous extract of B. trinervis,
which inhibited HSV-1 replication by 100% at 50-200 micrograms/mL, without
showing cytotoxic effects. Good activities were also found with the ethanol
extract of H. acuminata and the aqueous extract of E. articulatum, which
exhibited antiviral effects against both DNA and RNA viruses (HSV-1 and VSV,
respectively) at 125-250 micrograms/mL. The aqueous extracts of T. pusilla (100
250 micrograms/mL), B. teindalensis (50-125 micrograms/mL) and E. glutinosum (50
125 micrograms/mL) also inhibited the replication of VSV, but none of the
extracts tested had any effect on poliovirus replication.
PMID- 10190190
TI - Bioactivity studies of Salvia transsylvanica (Schur ex Griseb) grown in Egypt.
AB - Some pharmacological effects of the ethanol extract of Salvia transsylvanica
(Schur ex Griseb) were experimentally investigated. The tested extract of the
plant proved to be relatively nontoxic (LD50 = 4.437 g/kg b.wt.). The extract
induced significant analgesic, antipyretic, antiepileptic, antiinflammatory,
antiulcerogenic, as well as tranquillizing activities, besides increasing the
bleeding time and exhibiting no central skeletal muscle relaxant effect compared
with control groups and standard drugs.
PMID- 10190191
TI - Antimicrobial triterpenes from Ilex integra and the mechanism of antifungal
action.
AB - Antimicrobial triterpenes were isolated from the fruits of Ilex integra. Their
structures were elucidated by spectral data and identified as rotundic acid (1),
ulsolic acid (2) and peduncloside (3). Triterpene 1 showed significantly broad
antimicrobial activity against bacteria, yeast and filamentous fungi. The
antifungal activity of 1 was reversed by fatty acids. Cellular constituents
leaked from Candida albicans cells incubated with triterpene 1. These results
suggest that the antimicrobial activity of triterpenes in I. integra is due to a
change of membrane permeability arising from membrane lipid alteration.
PMID- 10190192
TI - Effects of 14-deoxyandrographolide and 14-deoxy-11,12-didehydroandrographolide on
nitric oxide production in cultured human endothelial cells.
AB - 14-deoxyandrographolide (DA) and 14-deoxy-11,12-didehydroandrographolide (DDA)
are two diterpenoids isolated from A. paniculata, a popular folk medicine used as
an antihypertensive drug in Malaysia. We have previously reported that DDA
exhibited a greater hypotensive effect in anaesthetized rats and a vasorelaxant
activity in isolated rat aorta, compared with DA. Their vasorelaxant activities
were mediated through the activation of the enzymes, nitric oxide synthase (NOS)
and guanylyl cyclase. The present study demonstrated that both DA and DDA
stimulated nitric oxide (NO) release from human endothelial cells. DDA compared
with DA caused a greater production of NO; this is in line with the finding of
the earlier study that the vasorelaxant effect of DDA was more dependent on
endothelium than DA.
PMID- 10190193
TI - Additional information to the in vitro antioxidant activity of Ginkgo biloba L.
AB - The in vitro antioxidant and free radical scavenging activity of the ethanol
extract from Ginkgo biloba L. was examined in different systems. The extract
showed hydrogen-donating ability, reducing power, copper-binding property, free
radical scavenging activity in a H2O2/.OH-luminol system and it could prevent the
autoxidation of linoleic acid. All these properties are involved in the overall
antioxidant activity of Ginkgo biloba which makes it suitable for the prevention
of human disease in which free radicals play an important role.
PMID- 10190194
TI - Inhibitory effects of isoflavones on lipid peroxidation by reactive oxygen
species.
AB - Possible inhibitory effects were investigated for four isoflavones, biochanin A,
daidzein, formononetin and genistein on lipid peroxidation by reactive oxygen
species. Biochanin A, formononetin and genistein inhibited lecithin peroxidation
which was induced by hydroxy radical generation, by interaction of haemoglobin
and hydrogen peroxide. Daidzein and formononetin inhibited lecithin peroxidation
which was induced by superoxide anion generation by xanthine-xanthine oxidase.
These results demonstrated that the differences in antioxidant activities of
isoflavones are dependent on the relation between their chemical structures and
reactive oxygen species.
PMID- 10190196
TI - Antiovulatory faculty of the flower of Malvaviscus conzattii.
AB - The methanol extract of the flowers of Malvaviscus conzattii was orally
administered in cycling unilaterally ovariectomized (ULO) rats at a dose level of
1 g/kg body wt/day for one or two cycles. The effect of the extract on the length
of the cycle and ULO-induced compensatory ovulation and hypertrophy of the
remaining ovary was assessed on the first oestrus following completion of
treatment. Although no adverse influence was observed on either of the
parameters, the cycle length was significantly prolonged and both the
compensatory phenomena underwent significant inhibition after treatment of the
extract for two consecutive cycles. In another experiment, the extract was found
to be ineffective in preventing exogenous gonadotropin(s)-induced ovulation in
immature and sub-adult rats. It is, therefore, suggested that the extract might
have interfered with the synthesis and/or release of gonadotropin(s) from the
pituitary while the ovarian utilization of gonadotropin(s) remained unaffected.
The LD50 of the extract was found to be 20 g/kg body wt.
PMID- 10190195
TI - Microvascular protective activity of flavonoid glucuronides fraction from Tulipa
gesneriana.
AB - A mixture of flavonoid glucuronides, consisting of 7-O-glucuronides of kaempferol
and quercetin 3-O-rutinosides, 3-O-gentiobiosides and 3-O-glucosides, was
isolated from the perianths of Tulipa gesneriana L. var. 'Paradae'. It showed
protective activity against the increased (both chloroform and histamine) skin
vascular permeability in rabbits. The protective effect, measured as the
reduction in leakage of Evans blue, was 59.8% after peritoneal treatment at a
dose of 25 mg/kg, while that of troxerutin was 45.5%.
PMID- 10190197
TI - Electrophysiological effects of Ageratum conyzoides L. on the guinea-pig heart.
AB - An extract obtained from the leaves of Ageratum conyzoides L. changed the
electrocardiogram, atrial impulse velocity, and coronary vessels resistance on
isolated guinea-pig heart. Electrocardiographic alterations were: (a) PR interval
increased from 80 +/- 1.4 ms to 105 +/- 14 ms (p < 0.01); (b) QT interval
decreased from 170 +/- 2 ms to 154 +/- 7 ms (p < 0.01); (c) heart rate decreased
from 170 +/- 17 bpm to 152 +/- 21 bpm (p < 0.01);(d) atrial impulse velocity
decreased from 51 +/- 2 cm/s to 45 +/- 3 cm/s (p < 0.01);(e) the time spent for
the impulse to be conducted from the atrium to the His bundle increased from 73
+/- 13 ms to 100 +/- 24 ms (p < 0.01). These effects disappeared after a washout.
PMID- 10190198
TI - Antiprotozoal activity of aporphine alkaloids isolated from Unonopsis buchtienii
(Annonaceae).
AB - On a preliminary screening, substantial leishmanicidal activity was observed for
the petroleum ether and alkaloidal extracts of the stem bark of Unonopsis
buchtienii, the alkaloids and sterols isolated from these were studied. Of the
alkaloids, liriodenine exhibited the highest activity against Leishmania major
and L donovani (IC100 = 3.12 micrograms/mL). On the other hand, O
methylmoschatoline and the petroleum ether extract without alkaloids showed an
interesting in vitro activity against Trypanosoma brucei with an IC100 of 6.25
micrograms/mL. The highest cytotoxic activities were found with the petroleum
ether extracts without alkaloids and with all alkaloids isolated (IC50 < 9
micrograms/mL for Vero cell line).
PMID- 10190199
TI - Model framework and principles of emergency management.
AB - If not handled quickly and effectively, animal health emergencies can create
significant problems for governments and industry. Placing strong emphasis on
preventing a disease incursion in the first instance through the judicious use of
quarantine and inspection measures will continue to be the major preventive
strategy. However, the discovery of new and emerging diseases, some of which may
already be present in a country or region, necessitates a rigorous emergency
outbreak response mechanism premised on thorough preparation for an emergency. A
generic approach to emergency management is the contemporary answer to preparing
for, and dealing with, unpredictable events. In essence, generic emergency
management plans encompass a set of core principles and key issues which are
relevant to a particular industry or commodity. These principles and issues are
then reflected in a model emergency management plan which guides participants
through the various stages of preparing for, and responding to, an emergency
situation and which forms the basis of more detailed farm/enterprise manuals and
individual job cards. The authors illustrate the integrated nature of the model
emergency management plan and the interrelationship with the core principles and
key issues of emergency management planning.
PMID- 10190200
TI - Management of animal health emergencies: general principles and legal and
international obligations.
AB - The Eighth Round of the General Agreement on Tariffs and Trade led to the
creation of the World Trade Organization and to the adoption of the Sanitary and
Phytosanitary (SPS) Agreement, thus considerably changing the rules of
international trade in animals and animal products. Animal health measures may
result in trade restrictions, but governments accept that these restrictions may
sometimes be necessary and appropriate to ensure food safety and animal health
protection. The SPS Agreement acknowledges the rights of governments to adopt
measure to protect human, animal and plant health. To ensure effective animal
health protection, without unjustifiable discrimination, the operational
procedures of Veterinary Services must be standardised, especially those
concerning disease notification, epidemiological information, certification for
international trade and management of animal health emergencies. Veterinary
Services must be further supported by a proper legislative framework and adequate
financial resources.
PMID- 10190201
TI - The involvement of the agriculture industry and government in animal disease
emergencies and the funding of compensation in western Europe.
AB - In Western Europe, the control and eradication of contagious animal diseases have
always been subject to government legislation. In the event of an outbreak, the
principal policy is 'stamping-out' (depopulation) of the infected herd. The owner
of the herd is usually awarded financial compensation. The authors provide an
overview of the involvement of the agriculture industry and government in animal
disease emergencies and the funding of compensation in Western Europe. In
particular, developments within the European Union are described, as illustrated
by a case study in the Netherlands. The economic consequences of a widespread
epidemic of classical swine fever (hog cholera) in the Netherlands in 1997 are
described. Evaluation of the epidemic demonstrated that special emphasis needs to
be placed on factors such as the high-risk period, animal movement, the attitude
of farmers towards risk and the structure of compensation. Epidemic disease
insurance schemes are considered to be a possible alternative in alleviating
certain financial losses caused by disease outbreaks.
PMID- 10190202
TI - Managing animal health emergencies through prevention and preparedness in
Oceania.
AB - Most countries in Oceania have adequate quarantine legislation, systems and staff
to prevent the introduction of new animal diseases. Surveillance and preparedness
for dealing with incursions of such diseases are less developed, except in those
countries with larger livestock populations. The degree of preparedness for
animal health emergencies in the different countries of the region reflects the
relative economic importance of exotic diseases to each particular country. For
those countries with significant populations of farm animals, appreciable efforts
and money are expended. However, in the smaller island countries, it can be
assumed that the likelihood of an exotic disease incursion is low and the impact
on the economy would be comparatively small. For these reasons, it would be
unreasonable to expect these countries to commit significant resources to develop
programmes equivalent to those in New Zealand and Australia, for example.
Nevertheless, there is a need for increased co-operation between countries in the
region. An assessment of each country to determine what resources are available
and how they may be used in various aspects of an animal disease emergency,
including co-ordinated information sharing, would enable smaller island countries
to be fully prepared in the case of an emergency.
PMID- 10190203
TI - Animal health emergencies: prevention and preparedness in Asia.
AB - Besides response and recovery, prevention and preparedness are the two critical
components of any contingency plan. The author discusses the various elements
which must be present in the prevention and preparedness plan of countries in
Asia. As the continent has such diverse peoples and veterinary infrastructures,
the actual plan may vary from one country to another, but must incorporate those
elements which are crucial to ensure the success of the preparedness plan.
PMID- 10190204
TI - Preventing and preparing for animal health emergencies in the Far East.
AB - The advantageous geographical location of Member Countries of the Office
International des Epizooties in the Far East (often islands or peninsulas)
provides better isolation than that of countries with terrestrial frontiers.
However, in the light of the explosive foot and mouth disease (FMD) outbreak
which occurred in Taipei China in 1997 after nearly 70 years of freedom from FMD,
countries in the Far East were alerted to the fact that while countries can be
physically far or isolated from the rest of the world, they do not necessarily
remain protected from epidemics and consequently need to be aware of effective
methods of management of animal health emergencies. Countries in the Far East
reviewed national management policies from the viewpoint of organisational
structure, surveillance system, diagnostic service, vaccine stock, funding,
legislation etc., and reconstructed these policies to ensure they were better
organised to prevent and control malignant diseases, such as FMD, in the case of
an emergency. With the accelerating and increasing movement of animals and animal
products internationally, countries in the region met in Tokyo in April 1998 to
discuss preparedness and management of animal health emergencies.
PMID- 10190205
TI - Dealing with animal disease emergencies in Africa: prevention and preparedness.
AB - Emergency preparedness planning for animal diseases is a relatively new concept
that is only now being applied in Africa. Information can be drawn from numerous
recent disease epidemics involving rinderpest, contagious bovine pleuropneumonia
(CBPP) and Rift Valley fever. These examples clearly demonstrate the shortcomings
and value of effective early warning with ensured early reaction in the control
of transboundary animal disease events. In concert, the Food and Agriculture
Organization (FAO), through the Emergency Prevention-System for Transboundary
Animal and Plant Pests and Diseases (EMPRES), and Organisation of African
Unity/Inter-African Bureau for Animal Resources (OAU/IBAR), through the European
Commission-funded Pan-African Rinderpest Campaign (PARC), have been actively
promoting the concepts and application of emergency preparedness planning and
should continue to do so under the proposed successor of PARC, namely: the Pan
African Programme for the Control of Epizootics (PACE). The potential partnership
between the normative function of the FAO in developing and promoting emergency
preparedness and the implementation of improved national and regional disease
surveillance by PACE and other partners could witness the commencement of more
progressive control of epidemic diseases in Africa and greater self-reliance by
African countries in coping with transboundary animal disease emergencies.
PMID- 10190206
TI - Disease prevention and preparedness in cases of animal health emergencies in the
Middle East.
AB - The animal health situation in the Middle East is particularly unfavourable, in
that this area is significantly exposed to many serious animal diseases. Typical
factors which contribute to this situation are illustrated with reference to an
outbreak of Rift Valley fever in Egypt from 1977 to 1980. The Middle East is ill
prepared to institute disease prevention and control measures, due to
deficiencies at both national and regional levels. Early disease detection,
diagnosis and reporting must become a priority, both within these countries and
among them. The author describes several regional animal health programmes which
are supported by international institutions and underlines their respective
importance.
PMID- 10190207
TI - Management of animal health emergencies in North America: prevention,
preparedness, response and recovery.
AB - Animal health emergency management (AHEM) is one of the most important issues
confronting the world today and is the key to both food security (safety,
quality, wholesomeness, affordability and abundance) and economic stability for
many countries. Although the primary objective of emergency management in each of
the countries of North America (Canada, Mexico and the United States of America
[USA]) is implemented through individual AHEM systems, North America shares four
common goals, as follows: preventing the introduction of foreign animal pathogens
into North America being prepared to manage the outbreak of a foreign animal
disease developing appropriate response strategies for control and eradication of
disease taking active measures to recover from the animal health emergency in
question. In the course of this paper, the authors provide an introduction to,
and overview of, AHEM in North America. Furthermore, they outline the general
infrastructure of prevention, preparedness, response and recovery strategies for
Canada, Mexico and the USA. Finally, the authors discuss the future of AHEM in
North America, concluding with a review of some of the joint activities currently
being conducted with regard to AHEM.
PMID- 10190208
TI - [Prevention of and attention to emergencies in South America].
AB - The authors review the policies designed to prevent and deal with animal health
emergencies which have been implemented in countries of South America. They
describe the evolution of the epidemiological situation of the continent, the new
arrangements for international trade in animals and products of animal origin
arising from the creation of the World Trade Organization (WTO), and the
consequences of such developments for livestock production in South America.
Veterinary systems used to prevent and deal with emergencies in the eleven OIE
Member Countries on the continent are described, together with emerging problems
which confront the Veterinary Services of the continent, namely: exotic diseases,
abnormal occurrence of endemic diseases subject to control programmes, faults in
food-safety mechanisms, diseases which have an environmental impact, and problems
connected with animal welfare. The emergencies which present the greatest risk to
South America are foot and mouth diseases, transmissible spongiform
encephalopathies, the porcine reproductive and respiratory syndrome, food
poisoning, Newcastle disease and fowl plague. Other problems are the appearance
of new strains of existing agents, and the presence of resistant individuals
among species of bacteria or harmful arthropods. The authors emphasise the need
to co-ordinate the prevention of emergencies with development work at the
international level, particularly regional and international agreements,
harmonization of procedures, progress in animal health and public health, risk
analysis, etc. These systems and methods of prevention have a contribution to
make in enhancing the potential of animal production in South America, and the
adoption of stricter health and quality standards, according to criteria
established by the WTO Agreement on the Application of Sanitary and Phytosanitary
Measures.
PMID- 10190209
TI - Disease prevention and preparedness: the Food and Agriculture Organization
Emergency Prevention System.
AB - In 1994, the Food and Agriculture Organization undertook to revitalise its
activities in the control of transboundary animal disease by establishing a new
special programme known as the Emergency Prevention System (EMPRES) against
transboundary animal and plant pests and diseases. The emphasis of the EMPRES
livestock component is placed on pre-empting outbreaks and losses experienced by
agriculture through the enhancement of local capacity to detect and react rapidly
to plague events. EMPRES concentrates on the co-ordination of the Global
Rinderpest Eradication Programme--a time-bound eradication programme--whilst
addressing the progressive control of the most serious epidemic diseases within a
broad framework of emergency preparedness. Programme activities are discussed in
relation to early warning, early reaction, facilitating research and co
ordination. In addition to rinderpest, particular attention has been paid to
contagious bovine pleuropneumonia, a re-emerging disease in Africa targeted for
strategic attention, and foot and mouth disease, for which co-ordinated regional
control in Latin America and South-East Asia has been initiated. Tactical
responses to other disease emergencies such as African swine fever, classical
swine fever (hog cholera), Rift Valley fever, peste des petits ruminants and
lumpy skin disease are described.
PMID- 10190210
TI - Bovine spongiform encephalopathy in Switzerland--the past and the present.
AB - The first case of bovine spongiform encephalopathy (BSE) in Switzerland was
diagnosed in November 1990, although the risk factors identified in the United
Kingdom were not all present in Switzerland. At 29 December 1998, a total of 282
BSE cases (all animals born in Switzerland), had been recorded. The number of
cases is declining, with fourteen cases diagnosed in 1998 (at 29 December 1998).
The measures taken are effective. However, the potential weakness in current
activities that allow the disease to exist are being evaluated. Further measures
to avoid even minimal risk for human and animal health will be taken if required.
Experience gained from the past indicates that it is necessary to review the
situation constantly and to inform the public and professionals regularly and in
a transparent manner.
PMID- 10190211
TI - Case studies of emergency management of screwworm.
AB - Screwworm myiasis, caused by infestation of even minor wounds by the obligative
parasitic larval stages of the New World screwworm (NWS) (Cochliomyia
hominivorax) or Old World screwworm (OWS) (Chrysomya bezziana) flies, is a major
cause of livestock morbidity and mortality in tropical and sub-tropical regions
of the world. The two parasites occur in different hemispheres but are remarkably
homologous. Animal health emergencies result from the invasion of new territories
by the parasites or, in the case of NWS, reinfestation of areas from which the
parasite had been eradicated after great effort and expense. The author reviews
the biology of the parasites and the effects of screwworm, in addition to
prevention of infestation upon the introduction of animals. Examples of three
programmes or events are described. The first is the eradication of previously
exotic NWS from an epizootic in Libya before the parasite spread to become
enzootic in the Mediterranean Basin and eventually other areas of the Eastern
Hemisphere. The second example reviews the serious consequences of the extension
of the range of OWS into Iraq where conditions at the time were favourable for
propagation and unfavourable for control. The third example describes the NWS
programme strategy in North and Central America which, for forty years, has been
to progressively achieve eradication and then protection of areas from north to
south on that continent, employing the sterile insect technique (SIT). Outbreaks
in areas where screwworm has already been eradicated divert costly programme
resources and slow progress southwards, and are considered emergencies. Some
problems encountered and the solutions found during the height of the eradication
programme in Mexico are described. Although to date eradication of screwworms has
only been accomplished with the application of SIT, this technique alone will not
eradicate the pest. The author describes other elements which are required to
control or eradicate screwworms. Programmes for this highly mobile parasite
encompass large geographic areas and consequently require active and continuous
international participation.
PMID- 10190212
TI - Rinderpest: a case study of animal health emergency management.
AB - The history of rinderpest and control of the disease in Africa and Asia is
reviewed briefly. The present distribution of rinderpest virus in relation to its
phylogenetic lineages is presented. Rinderpest-free countries bordering
rinderpest-infected countries are considered to be under permanent threat of a
transboundary rinderpest incursion and therefore face continuous and serious
emergency situations. The nature of these emergencies in relation to the
remaining foci of the three lineages is described. It is argued that the Global
Rinderpest Eradication Programme (GREP) eradication strategies now need to focus
on the use of epidemiological studies to define foci of infection and guide
targeted, pulsed vaccination campaigns rather than broad, routine vaccination.
The emergency posed by the re-emergence of African lineage 2 virus in East Africa
and the challenge of mild rinderpest is explored in some detail as a phenomenon
which may be more widespread than has been assumed. Points at which the future of
GREP is threatened are illustrated and means of removing some of the dangers are
suggested. The lessons which need to be learnt from the experience of the Indian
National Project on Rinderpest Eradication and the Pan-African Rinderpest
Campaign are discussed, including the value of strengthening surveillance systems
in accordance with the Office International des Epizooties Pathway and how to
cope with the problem associated with cryptic foci of rinderpest persistence-
perhaps the greatest challenge facing GREP. The value of vaccine buffer zones is
considered in detail and the authors conclude that unless those zones are of
considerable depth and are well maintained, they are unlikely to prevent
dissemination of the virus. The role of emergency preparedness planning in
preventing the spread of rinderpest is discussed, with the understanding that
effective surveillance, as a component of emergency preparedness planning, is
safer than vaccination as a means of ensuring that the disease does not re-enter
or penetrate a population. The swift initiation of a programme for the
eradication of rinderpest from Pakistan is seen as the key issue in dealing with
the Asian lineage rinderpest emergency. Development and implementation of
strategies with the benefit of experience gained in Africa and India could
provide a rapid resolution of the emergency.
PMID- 10190213
TI - The circumstances surrounding the outbreak and spread of equine influenza in
South Africa.
AB - Equine-2 influenza A virus (H3N8) infection first occurred among naive horses in
South Africa in December 1986. The virus was introduced following the importation
of six horses from the United States of America. While the release of in-contact
horses from quarantine three days after the arrival of these six horses played a
role in the rapid spread of the disease in South Africa, other outbreaks of
disease were associated with viral introduction by personnel or contaminated
instruments. The control measures and implications of the introduction of equine
influenza to South Africa are also discussed.
PMID- 10190214
TI - Managing an animal health emergency in Taipei China: foot and mouth disease.
AB - Taipei China had been free from foot and mouth disease (FMD) over 68 years before
the disease occurred in March 1997. The first suspected case was recorded on a
pig farm in the Hsinchu Prefecture on 14 March 1997. Based on clinical signs,
gross histopathological findings, and results of enzyme-linked immunosorbent
assays and reverse-transcriptase polymerase chain reaction tests, diagnosis of
FMD was confirmed by the Taiwan Animal Health Research Institute on 19 March 1997
and was reconfirmed by the FMD World Reference Laboratory in Pirbright (United
Kingdom), on 25 March 1997. By the end of July 1997, 6,147 pig farms (about a
quarter of the pig farms in Taipei China), were affected. The disease was well
under control within two months by means of stamping-out and blanket vaccination.
The Government purchased 21 million doses of inactivated oil-adjuvant FMD
vaccine, which allowed for two injections per pig and one injection of other
cloven-hoofed animals. Before the vaccine was used, the stamping-out policy was
implemented, ensuring that all pigs in the affected farms were destroyed. After
blanket vaccination, a partial stamping-out policy was adopted, i.e. only pigs
showing clinical signs were destroyed.
PMID- 10190215
TI - Dealing with unexpected or unknown emergencies: examples of Australian
approaches.
AB - Emergencies may derive from unknown agents or an unusual incident from a known
exotic or endemic disease agent. Veterinary administrations must be able to deal
rapidly with these occurrences, to allay public fears, media interpretations, and
environmental or political concerns. The emergency approach to deal with such
incidents should be based on well-established disease control principles. In
dealing with the unknown, veterinary authorities must take a comprehensive
approach to managing the problem. Events such as the bovine spongiform
encephalopathy in the United Kingdom and Europe have shown that management
becomes much more complex when animal health events also involve human disease.
The absence of scientific knowledge creates an environment of speculation, fear
and mistrust, which may seriously erode the ability of animal health authorities
to respond as they would wish. An established structure which identifies the
roles and responsibilities of key players and clearly states where accountability
for handling the situation ultimately rests is essential. In addition, emergency
plans which have been tested by training exercises, for example, are critical.
Other operators who could be involved in the management of emergencies must also
be fully aware of their roles in the event of a problem. Over recent years,
Australia has experienced a number of new diseases which have had to be handled
in an environment of uncertainty and in conditions where knowledge was lacking.
The authors briefly outline a number of these incidents as case studies and list
the key factors involved in dealing with each emergency.
PMID- 10190216
TI - Successful aquatic animal disease emergency programmes.
AB - The authors provide examples of emergency programmes which have been successful
in eradicating or controlling certain diseases of aquatic animals. The paper is
divided into four parts. The first part describes the initial isolation of viral
haemorrhagic septicaemia (VHS) virus in North America in the autumn of 1988 from
feral adult chinook (Oncorhynchus tshawytscha) and coho salmon (O. kisutch)
returning for spawning. The fish disease control policies at both State and
Federal levels in the United States of America required quarantine and emergency
eradication measures upon the finding of certain exotic fish pathogens, including
VHS virus. The procedures for emergency plans, destruction of stocks and
disinfection of facilities are described, as well as challenge experiments with
the North American strains of VHS virus and the detection of the virus in marine
fish species (cod [Gadus macrocephalus] and herring [Clupea harengus pallasi]) in
the Pacific Ocean. The second part of the paper outlines the aquatic animal
legislation in Great Britain and within the European Union, in regard to
contingency plans, initial investigations, action on the suspicion of notifiable
disease and action on confirmation of infection. The legal description is
followed by an account of an outbreak of viral haemorrhagic septicaemia in turbot
(Scophthalmus maximus) in Great Britain, including the stamping-out process at
the affected farm and investigations conducted to screen other farms in the
vicinity for possible infection. The third part provides a historical review of
the build-up of infectious salmon anaemia (ISA) in Norway and the attempts to
control the disease using legal measures in the absence of detailed knowledge of
the aetiology, epizootiology, pathogenesis, etc. of the disease. The measures
taken show that the spread of ISA can be controlled using restrictions on the
movement of fish, disinfection procedures, etc. However, acceptance and
understanding of the chosen strategy by the fish farmers is a pre-requisite to
reach that goal. Finally, the paper summarises future needs for national and
international legislation, including the development of standard approaches for
control, the creation of appropriate infrastructures and a better understanding
of the epidemiology of aquatic animal diseases.
PMID- 10190217
TI - Approaches to managing aquatic animal health in Australia.
AB - Despite a rapid and continuous expansion in aquaculture industries, Australia has
not experienced significant disease emergencies in farmed aquatic animal
populations. However, recent events in relation to wild, farmed, native and
introduced aquatic animals have provided warning signals. The development of a
national response mechanism for fisheries and aquaculture emergencies became a
high priority following the pilchard mortality outbreak in 1995. In terms of more
general policy, a special Task Force has provided a framework for managing exotic
pests, weeds and diseases and identifying key principles and issues. This Task
Force also recommended closer consultation between relevant industry
organisations and government agencies. The authors describe the framework of the
comprehensive five-year national strategic plan for aquatic animal health
('AQUAPLAN') developed by Australia, and the aquatic animal disease veterinary
emergency plan developed within this framework ('AQUAVETPLAN').
PMID- 10190218
TI - [The role of the veterinarian during natural disasters].
AB - After a reminder of the main types of natural hazards that can lead to genuine
disasters, the author examines the impact of such disasters on animal health. The
conceptual approach to various groups of animals in a disaster situation is
explained, as well as the direct and indirect effects of such disasters.
Preparatory measures are presented within the general framework of prevention and
forecasting, together with the veterinary measures to be implemented. Training of
veterinarians and planning of activities are described in detail. A traditional
approach to organising large-scale assistance is advocated, based on the
competence of the personnel involved and a predefined hierarchical organisation.
The author then describes veterinary actions to be taken in a disaster situation
where emergency aid is required. Particular reference is made to providing
assistance to save human lives, including search operations by dog teams for
buried victims, and the subsequent phase of restoring human activities, during
which assistance to animals is taken into account. Inter-ministerial co
ordination using crisis units and priority management implying real political
choices are discussed. Finally, based on the example of the operational
organisation of the French Civil Defence, the author describes the support
available to Veterinary Services and the potential involvement of the profession,
in particular veterinary officers attached to the emergency fire service.
PMID- 10190219
TI - Emergency management of disasters involving livestock in developing countries.
AB - Different disasters have similar consequence on the health and welfare of
livestock. Numerous geophysical disasters can exacerbate epizootics, resulting in
the deaths of many animals and the reduction of production efficiency. These
disasters also present a considerable threat of spoilage of processed foods,
endangering public health. Furthermore, large-scale disasters involving animals
can modify the long-term stability of national economies, the environment and
social structures. The authors discuss the vulnerability of the livestock
industry to natural disasters and the impact of floods, droughts and
transboundary diseases and pests on national economies. Examples are given on how
some losses can be avoided, evaluated and compensated. The role of the
veterinarian is presented in relation to work conducted by other relief
organisations in cases of emergency. In developing countries, mitigation
programmes should focus on strengthening global animal health services.
Preparedness needs to be community based, with education provided in a timely
manner. Effective recovery from disasters should be based on mitigation
programmes, including international trade and mutual aid agreements between
neighbouring countries to supply appropriate goods and environmentally and
culturally appropriate breeds of livestock. Disaster relief for the care of
livestock should be recognised as a form of humanitarian assistance, given the
benefits to be derived for public health and the socio-economic implications of
successful intervention.
PMID- 10190220
TI - New antipsychotic drugs: special issues and indications. Symposium proceedings.
Marco Island, Florida, USA. 20-21 February 1998.
PMID- 10190221
TI - Schizoaffective disorder: role of atypical antipsychotics.
AB - The pharmacologic treatment of schizoaffective disorder is one of the least well
studied areas of contemporary pharmacotherapy. The authors review available
literature on the traditional pharmacologic treatment of schizoaffective
disorder, new data on the atypical antipsychotics, and potential pharmacologic
mechanisms by which these new agents may produce thymoleptic activity.
PMID- 10190222
TI - Anxious-depressive symptoms in schizophrenia: a new treatment target for
pharmacotherapy?
AB - Schizophrenia patients frequently manifest concurrent anxiety and depressive
symptoms. Such features exhibit prognostic relevance (i.e. patient morbidity and
mortality). Despite this, they remain relatively unstudied and are not
universally viewed as therapeutic targets. Conventional neuroleptic agents may
not improve these symptoms and may actually worsen them. However, with the
introduction of novel pharmacological agents for the treatment of schizophrenia,
there is reason to believe that a wider spectrum of symptomatology may be
treatment responsive. In this post hoc analysis of the Brief Psychiatric Rating
Scale anxiety-depression cluster, olanzapine therapy was associated with a
significantly greater baseline-to-end-point improvement in the cluster compared
with haloperidol therapy among 1996 randomized, double-blind subjects. Moreover,
the olanzapine treatment-effect advantage included both direct (mood symptoms)
and indirect (positive, negative, and extrapyramidal symptoms) elements. This
study concluded that the novel pharmacology of olanzapine delivered greater
therapeutic activity in anxious and depressive symptoms accompanying
schizophrenia than did the conventional dopamine D2 antagonist haloperidol.
PMID- 10190223
TI - Atypical antipsychotics in the treatment of the persistently aggressive psychotic
patient: methodological concerns.
AB - Aggressive behavior of psychotic patients impacts all aspects of their clinical
care. Better treatments to address this problem are needed, and atypical
antipsychotics, such as clozapine, risperidone, and perhaps quetiapine, have
shown promise. However, studying the psychopharmacology of aggression is
difficult because of the many methodological problems that arise in the design of
appropriate clinical trials. These include imprecise definitions of aggression,
the difficulty of measuring outcome because of the relative rarity of aggressive
events, bias in the selection of patients for study, inadequate and inappropriate
control groups, and inattention to comorbidities and concomitant medications in
analyzing results. Since the usual outcome measure is the aggressive event rate,
a large sample size and lengthy baseline and trial periods are required when this
rate is low. Furthermore, formidable practical and ethical obstacles interfere
with the many sound techniques (e.g. randomization) used in typical designs of
psychopharmacological clinical trials. Current research methods should be
modified and new ones developed in order to progress in assessing the
antiaggressive effects of treatments.
PMID- 10190224
TI - Toward a rational pharmacotherapy of comorbid substance abuse in schizophrenic
patients.
AB - The prevalence of substance abuse is elevated among schizophrenic patients. When
free of illicit substances and sober, substance-abusing schizophrenic patients
may have a better prognosis than other frequently hospitalized schizophrenic
patients. However, the cost of substance abuse is great in terms of
rehospitalization, homelessness, risk of other medical illness, disruption of
social and vocational function, exacerbation of symptoms, suicide, and increased
health care expenses. Important recent developments in medications for reducing
substance abuse in nonschizophrenic populations make it timely to consider
factors that might contribute to substance abuse among schizophrenic patients.
This review will focus on substances most frequently abused by schizophrenic
patients: nicotine, alcohol, cannabis, and psychostimulants. It concentrates on
two conceptual foci: "self-medication hypotheses" and "comorbid addiction
vulnerability hypotheses". The relationship between these hypotheses and possible
pharmacotherapeutic approaches for substance-abusing schizophrenic patients will
be considered.
PMID- 10190225
TI - Cognitive improvement in schizophrenia with novel antipsychotic medications.
AB - The syndrome of schizophrenia often includes negative symptoms and severe
cognitive deficits that are resistant to change with conventional
pharmacotherapy. The efficacy of clozapine in the reduction of the negative
syndrome has prompted a series of studies implicating circumscribed cognitive
improvements. Restrictions on the use of clozapine have encouraged the
development and introduction of novel compounds with a clinical efficacy profile
similar to clozapine that are hoped also to have beneficial cognitive effects.
The present review summarizes studies of the cognitive efficacy of novel
antipsychotic medications, particularly in regard to issues in experiment design
and study implementation that might facilitate additional research. Although
preliminary support exists for relatively circumscribed improvement of cognitive
status with the use of clozapine and risperidone--and more general improvement
with the use of olanzapine--specific inferences relating cognitive change to
particular treatments will remain speculative until more sophisticated
investigations are completed. The present review emphasises the most relevant
design limitations in past studies to provide practical suggestions for the
implementation of subsequent investigations Previous results have established the
possibility of a medication-based change in cognitive status in schizophrenia
Future research will determine the validity of these changes, the cerebral
mechanism involved, and their significance to improved prognosis.
PMID- 10190226
TI - Tardive dyskinesia and atypical antipsychotic drugs.
AB - Typical antipsychotic agents produce central nervous system effects, especially
extrapyramidal symptoms (EPS) and tardive dyskinesia (TD). Nearly every patient
who receives neuroleptic therapy has one or more identifiable risk factors for
TD, among the most significant of which are older age, female gender, presence of
EPS, diabetes mellitus, affective disorders, and certain parameters of
neuroleptic exposure (i.e. dose and duration of therapy). The typical course of
TD is a gradual onset after several years of drug therapy, followed by slow
improvement or remission, but a large number of patients have persistent TD with
irreversible symptoms. In the management of TD, the patient's mental status is of
primary concern. Currently, no uniformly safe and effective therapies for TD
exist, though a variety of therapeutic agents, including some of the atypical
neuroleptics, have been reported to treat TD successfully in some patients.
Because TD liability is so much lower with novel antipsychotic therapy, all
patients who have TD or are at risk for TD, as well as EPS, should be considered
candidates for switching to these new drugs.
PMID- 10190227
TI - Prolactin and antipsychotic medications: mechanism of action.
AB - Until the introduction of the first atypical antipsychotic, clozapine, in 1975,
hyperprolactinemia was assumed to be an inevitable consequence of treatment with
any antipsychotic agent. Now we know that atypical antipsychotics such as
clozapine, olanzapine, quetiapine, sertindole, and ziprasidone are not associated
with significant prolactin increase. These new antipsychotics appear to spare
dopamine blockade within the brain's tubero-infundibular tract, a dopamine
pathway that also controls prolactin secretion. Since the release of prolactin is
tonically inhibited by the hypothalamus, with dopamine acting as the prolactin
release-inhibiting factor, any disruption of the connection between the
hypothalamus and the pituitary gland is associated with hyperprolactinemia. Other
factors that can increase prolactin secretion are also reviewed (e.g. estrogens,
thyroid-releasing factor, vasoactive intestinal peptides, opioids, surgery,
illness such as epilepsy or herpes zoster infection, and psychic or physical
stress). Prolactin levels are at their highest 1-2 hours before waking, and early
waking interrupts its secretion. The major effects of hyperprolactinemia in women
are amenorrhea, cessation of normal cyclic ovarian function, loss of libido,
occasional hirsutism, and increased long-term risk of osteoporosis. The effects
in men are impotence, loss of libido, and hypospermatogenesis. Current data
indicate that conventional antipsychotics, as well as high doses of risperidone
(> 6 mg/day), increase prolactin levels to a range associated with sexual
dysfunction in nonpsychiatric patients. The lack of prolactin elevation reported
with the atypical antipsychotics is believed to be due to their much greater
specificity, which results in less blockade of dopamine receptors in the tubero
infundibular pathway.
PMID- 10190228
TI - Neuroleptic-induced hyperprolactinemia.
AB - Neuroleptic-induced hyperprolactinemia (NIHP) has been a 'cost' of traditional
antipsychotic therapy. Because all of the traditional neuroleptics are capable of
elevating serum prolactin, clinicians have had to accept the implications of NIHP
along with the antipsychotic's efficacy. Accordingly, the clinical consequences
of NIHP have received limited attention. With the introduction of some of the
new, more highly selective mesolimbic and mesocortical dopamine-blocking,
prolactin-sparing antipsychotic drugs, NIHP may now be prevented or minimized.
Given this possibility, it becomes more important than ever that clinicians
understand both the short- and long-term consequences of hyperprolactinemia and
current management approaches.
PMID- 10190229
TI - Antipsychotic drugs and relapse prevention.
AB - Strategies for preventing relapse during the maintenance or stable phase of
schizophrenia are discussed for both conventional and newer antipsychotics. For
conventional agents, strategies focus on finding dosages that minimize
antipsychotic drug side effects and provide adequate protection against psychotic
relapse. Although few studies are available to compare older and newer
antipsychotics for preventing relapse, there are reasons for proposing that newer
drugs will be shown to be superior. Because of their milder side effects,
clinicians can choose drug dosages that provide maximum protection against
relapse. Further, since patients on the newer drugs are likely to experience
fewer discomforting side effects, they may be more likely to take their
medications as directed. Other potential advantages of the newer drugs over the
older drugs include the likelihood that they are more effective against negative
and cognitive symptoms of schizophrenia.
PMID- 10190230
TI - Dual diagnosis of substance abuse in schizophrenia: prevalence and impact on
outcomes.
AB - Comorbid substance abuse disorders have emerged as one of the greatest obstacles
to the effective treatment of persons with schizophrenia. Estimates of the
prevalence of such comorbidity vary, but as many as half of persons with
schizophrenia may suffer from a comorbid drug or alcohol disorder. Younger age,
male gender, and lower educational attainment are associated with greater risk
for addiction. Persons with schizophrenia and comorbid addiction tend to have an
earlier onset of schizophrenia than do those without comorbid addiction. Research
does not support a link between specific symptoms of schizophrenia and choice of
abused drugs. Rather, drug choice is correlated with the pattern of ambient drug
use in the community. Comorbid substance disorders are associated with a variety
of poorer outcomes, including increased psychotic symptoms, poorer treatment
compliance, violence, housing instability and homelessness, medical problems
(including human immunodeficiency virus infection), poor money management, and
greater use of crisis-oriented services that result in higher costs of care.
Considerable progress has been made over the past decade in understanding the
need to integrate substance abuse treatment and mental health treatment to
provide more effective care for this population.
PMID- 10190231
TI - Pharmacoeconomic studies of atypical antipsychotic drugs for the treatment of
schizophrenia.
AB - The pharmacoeconomic evaluation of atypical antipsychotics for patients with
schizophrenia requires focus on both clinical and quality of life effects and
impact on the cost of medical resources. The results of pharmacoeconomic studies
help clinicians and health care decision makers identify treatments that provide
the most benefit to patients at the most acceptable cost. The cost-effectiveness
of antipsychotic drugs has been evaluated using noncontrolled, mirrorimage (i.e.
retrospective/prospective) cohort study designs; clinical decision analysis
models; and randomized clinical trials. The current pharmacoeconomic evidence
suggests that clozapine is a cost-effective therapy for neuroleptic-refractory
schizophrenia and that although olanzapine and risperidone therapy may be cost
neutral, they improve outcome in patients treated for schizophrenia.
PMID- 10190232
TI - [Use of muramyl peptides in viral vaccines].
AB - Discusses the selective activation of HIV replication under the effect of various
muramylpeptides with immunostimulating effect. Emphasizes the significance of
selecting adjuvants inducing no HIV activation, particularly in cases when the
vaccines are intended for seropositive subjects.
PMID- 10190233
TI - [Identification of California serogroup viruses (Bunyaviridae, Bunyavirus) using
monoclonal antibodies to Inkoo virus].
AB - Five types of monoclonal antibodies to inkoo virus were used to detect antigenic
relationships between 12 Inkoo-like strains and the prototype Inkoo virus strain.
Eight strains were found antigenically very close or identical to Inkoo virus,
and the rest 4 are probably original variants (viruses) of California serogroup.
PMID- 10190234
TI - [Preparation of single-chained antibodies to surface glycoprotein E from tick
borne encephalitis virus].
AB - A single-stranded antibody gene scFv was designed on the base of cDNA fragments
of genes coding for variable domains of heavy and light chains of MAb E6B to tick
borne encephalitis glycoprotein E. High production of stable soluble scFv was
reproduced in Escherichia coli cells. Recombinant antibodies bound to
antiidiotypical antibodies to initial MAb E6B and to recombinant virus protein E.
Competitive analysis showed that single-stranded antibodies inhibited reaction
between MAb E6B and protein E. These results confirm the formation of scFv with
the original antigen-binding specificity towards tick-borne encephalitis virus
glycoprotein E.
PMID- 10190235
TI - [Expression of receptors for human alpha- and gamma-interferons on the surface of
peripheral blood mononuclear cells in viral infections].
AB - Expression of receptors on peripheral blood mononuclears of donors and patients
with viral infections during therapy was studied using FITC-labeled monoclonal
antiidiotypical antibodies with the "internal image" of human alpha- and gamma
interferons and monoclonal antibodies to these interferons. Activation of the
immune system caused by infection modifies the expression of interferon receptors
and leads to appearance of membrane-bound interferons, mainly gamma-interferon.
PMID- 10190236
TI - [Frequency of acute cytomegalovirus infections among people of differing age
groups].
AB - The incidence of cytomegalovirus (CMV) infection was assessed from the presence
of anti-CMV IgM in the sera of 1312 children of different age and 250 adults by
the Labsystems enzyme immunoassay kit. CMV-specific IgM are rare in newborns
(1.3%), but their incidence increases to 5% during the first year of life. These
antibodies occur in 5-6% preschool and schoolchildren. The incidence of acute CMV
infection is the highest in adults: 15%.
PMID- 10190237
TI - [Serological and epidemiological features of infections, caused by Epstein-Barr
virus, in the Republic of Belarus].
AB - Incidence and spectrum of antibodies to diagnostically significant Epstein-Barr
virus antigens are studied by enzyme immunoassay and immunodot method in 178
subjects living in areas with different levels of radioactive contamination. A
tendency to earlier infection of children and a more frequent reactivation of
latent infection in adults are observed at contaminated territories in comparison
with the "clean" regions. The authors propose immunoecological monitoring aimed
at timely detection of groups at risk of immunodeficiencies and neoplastic
diseases.
PMID- 10190238
TI - [Stabilization of influenza virus with antioxidants].
AB - Antioxidant stabilizers can be selected by the effects of their components on
biological activity of influenza viruses and their antioxidative effects on
influenza virions and model membranes--liposomes.
PMID- 10190239
TI - [Antitumor activity of cold-adapted strains of influenza virus in a model
transformed murine tumor cells].
AB - Influenza virus suppressed tumor growth after injection to tumor zone in a dose
of 7-8 lg EID50, as was shown for two continuous mouse tumor cell strains,
Ehrlich's carcinoma and L-1210 lymphoma. Influenza virus strains differed by
their antitumor activity which correlated with their interferonogenic activity.
Antitumor activity of influenza virus depended on the site of application, dose
of the virus, and interferonogenic activity. Virus therapy of tumors stimulated
specific cytotoxic activity towards tumor antigens.
PMID- 10190240
TI - [Effect of mutilus hydrolysate in Aleutian disease of minks].
AB - Addition of mutilus hydrolysate MIGI-K to rations of minks with virus
plasmacytosis involving grave immunological disorders led to changes in the ratio
of serum protein fractions and in the differential blood count. Normalization of
the protein spectrum of minks with Aleutian disease apparently inhibits the
development of disorders caused by hypergammaglobullnemia.
PMID- 10190241
TI - [Effect of gentamycin on persistence of tick-borne encephalitis].
AB - Effect of gentamicin, an aminoglycoside antibiotic, on the persistence of tick
borne encephalitis (TBE) virus in Syrian hamsters and Macaca iris in remote
periods (70-434 days) after inoculation is studied. Attempts at virus isolation
from animals treated with gentamicin failed. Unlike other aminoglycosides, e.g.
streptomycin, gentamicin exerted no immunodepressive effect; moreover,
immunocorrection was observed in some experiments on monkeys and hamsters. None
of the 10 previously tested antibiotics elicited such an effect or inhibited the
persisting TBE virus. Morphological study of the central nervous system in
hamsters and monkeys showed that injection of gentamicin did not cause an
exacerbation of chronic encephalitis. The mechanism of immunocorrecting effect of
gentamicin is to be further investigated.
PMID- 10190242
TI - [Immunodepressive effect of measles and parotitis virus in vitro].
AB - Mechanisms of suppressive effect of measles and parotitis virus on lymphocyte
proliferation and cytolytic activity of natural killers are studied in vitro.
Both viruses exert a weak mitogenic effect on human blood lymphocytes and at the
same time suppress their response to phytohemagglutinin stimulation in vitro.
Suppressive effect of measles virus is more expressed than of parotitis virus.
Moreover, measles virus suppresses lysis of human blood killer target cells. The
suppressive effect manifests as early as in 1 h and increases after 3 h of
natural killer cell contact with measles virus.
PMID- 10190243
TI - [Structural changes in the gypsy moth (Ocneria dispar L.) hemogram in
polyhedrosis].
AB - Structural changes in hemogram of Gypsy moth larvae from a population in the
phase of quantity increase are studied morphometrically and cytochemically. The
counts of granulocytes and prohemocytes are increased, as are the counts of
hemocytes possessing phenol oxidase activity and hemocytes reducing nitroblue
tetrazolium. Atypical virus morphogenesis is observed.
PMID- 10190244
TI - [Development of a rapid method, based on the latex agglutination reaction, for
diagnosing carnivore plaque].
AB - A highly effective rapid method for detecting carnivore plague virus antigen in
dogs, based on the latex agglutination test, is developed. Latex conjugate is
synthesized on the base of polystyrene suspension, representing a copolymer of
styrene and methacrylic acid. The immunospecific reagent is gamma-globulin
fraction of rabbit serum containing antibodies specific to carnivore plague
virus. The resultant latex conjugate can be used in practical veterinary as a
diagnostic agent for screening dogs for carnivore plague virus.
PMID- 10190245
TI - Prevalence and clinical importance of Helicobacter pylori infection in patients
after partial gastric resection for peptic ulcer disease. A prospective
evaluation of Helicobacter pylori infection on 50 resected patients compared with
matched nonresected controls.
AB - There have been only a few surveys on the prevalence of persistent Helicobacter
pylori (Hp) infection in patients who have undergone surgery for peptic
ulceration. The aim of the study was to evaluate the prevalence and clinical
importance of Hp infection after partial gastric surgery due to peptic ulcer
disease. METHODS: We examined 50 patients who had partial gastric resection for
peptic ulcer disease and years later underwent upper gastrointestinal (GI)
endoscopy. 50 controls matched with respect to indication for GI endoscopy, age
and gender were also studied. Three specimens from the fundus of gastric remnant
were examined for Hp infection (histology and rapid urease test). The prevalence
of Hp infection and pathology findings were compared between the two groups using
chi-square statistics. RESULTS: 32 men and 18 women were examined (40 x BII, 10 x
BI). The prevalence of Hp infection was 38% in the resected group compared to 60%
in the control group (p = 0.015). We found a significant association (p = 0.0004)
between Hp infection and endoscopic findings in the control group but not in the
group of partially resected patients (p = 0.66). CONCLUSION: The prevalence of Hp
infection in hospitalized patients with partial gastric resection is
significantly lower than in matched controls. Hp infection does not play a
significant pathogenic role in recurrent ulcer after partial gastric resection in
these patients.
PMID- 10190247
TI - [Sonographic detection of perihepatic lymph nodes: technique and clinical value].
AB - Sonographic detection of perihepatic lymphadenopathy by transabdominal ultrasound
is helpful in the diagnosis of acute and chronic liver disease but
differentiation between benign inflammatory and malignant disease is not
possible. The diagnostic value of perihepatic lymphadenopathy has been evaluated
in patients with chronic hepatitis C and primary biliary cirrhosis. In patients
with chronic hepatitis C enlargement of perihepatic lymph nodes is associated
with viremia and is predictive for the presence of severe inflammatory activity
with and without cirrhosis. In retrospective studies it could be shown that
patients with chronic hepatitis C without response to antiviral therapy do not
normalize the size of perihepatic lymph nodes. Future prospective studies have to
evaluate whether successful antiviral therapy together with histological
improvement will be reflected in an decline of perihepatic lymph node size. In
patients with primary biliary cirrhosis the total perihepatic lymph node volume
reflect histological stages, i.e. larger lymph nodes are observed in more
advanced disease. The mechanism of portal lymphadenopathy in patients with acute
and chronic liver disease is unknown. Viral, bacterial infections, and
immunological causes are potential etiopathological factors in periportal
lympadenopathy. Malignant causes of perihepatic lymphadenopathy have also to be
considered.
PMID- 10190246
TI - Lack of association between HLA-DRB1 alleles of the major histocompatibility
complex and p-ANCA status or clinical characteristics in patients with ulcerative
colitis.
AB - INTRODUCTION: An association between different HLA-subtypes and ulcerative
colitis has been described in various study populations of different ethnic and
geographic background. Moreover, a correlation between HLA-DR2 and ulcerative
colitis, in particular p-ANCA-positive ulcerative colitis, was reported. Thus,
the present study aimed on the correlation of HLA-DRB1* alleles with the presence
of p-ANCA and clinical characteristics in individuals of southern german descent.
PATIENTS AND METHODS: The study population comprised 56 patients with ulcerative
colitis and 177 healthy controls. HLA-DRB1* alleles were assessed by use of the
dot blot method. Autoanti-bodies were visualized by indirect immunofluorescence
on ethanol-fixed neutrophils. RESULTS: The allele HLA-DRB1*12 was more frequent
in patients with ulcerative colitis (p = 0.01). After correction for the number
of alleles tested (n = 16) statistical significance was no longer preserved. A
weak association between the presence of HLA-DR5 and the detection of p-ANCA in
ulcerative colitis was found (p = 0.0375). After correction for the number of
comparisons (n = 10) no associations between HLA-DR antigens and the presence of
p-ANCA remained. Furthermore, no significant correlations between clinical
characteristics of ulcerative colitis and HLA-DR antigens were detected.
DISCUSSION: Genes encoding for HLA-DR antigens are unlikely to have an impact on
the heredity and the presence of disease phenotypes of ulcerative colitis in a
study population of southern german descent.
PMID- 10190248
TI - Simultaneous MALT-type lymphoma and early adenocarcinoma of the stomach
associated with Helicobacter pylori gastritis.
AB - We report about two cases of combined gastric lymphoma and gastric carcinoma with
one of them representing a case of early gastric high grade B-cell lymphoma of
mucosa-associated lymphoid tissue (MALT) with co-existing early gastric
adenocarcinoma. In contrast to most previously reported similar cases, in both of
our cases the definitive diagnosis of gastric lymphoma and carcinoma was obtained
preoperatively. This, however, seems to be in future times an essential
prerequisite for employing minimal invasive methods such as eradication therapy
in the case of diagnosed early lymphoma and endoscopic treatment for early
gastric carcinomas. These methods have been proven to be an effective and
beneficial alternative treatment especially with regard to the life quality of
the patients.
PMID- 10190249
TI - [Granulomatous hepatitis and myelitis: an unusual manifestation of extrapulmonary
sarcoidosis].
AB - Sarcoidosis is a chronic multisystem disorder of unknown cause characterized by
the presence of noncaseating epitheloid granulomas and derangement of the normal
skin architecture. Though an array of organs may be affected by the disease the
most common site of affection is the lung. An extrathoratic manifestation is
rare. We describe a 66-year-old patient who was admitted to our hospital because
of weight loss and hepatomegaly. A thorough examination revealed the diagnosis of
a granulomatous hepatitis characterized by a markedly elevated alkaline
phosphatase concentration of 1,490 U/I. A drug-induced hepatitis could be
excluded and no evidence was found for the existence of a bacterial or viral
infection or an autoimmune disorder. An ERCP revealed a normal common bile duct
and normally branching small intrahepatic ducts. The patient was discharged with
the diagnosis of a biliary cirrhosis. Half a year later the patient was
readmitted to the hospital because of severe intestinal bleeding due to
pancytopenia. A bone marrow biopsy showed infiltration of the marrow by
granulomas. A histiocytosis X could be ruled out. The diagnosis of an
extrathoracic sarcoidosis was assumed and a therapy with prednisone was started.
Within six weeks the blood count normalized. After 18 months the serum alkaline
phospatase concentration also normalized and no granulomas were found in the bone
marrow. The case demonstrates that pancytopenia in sarcoidosis is not due to bone
marrow failure.
PMID- 10190250
TI - [Mechanisms and applications of oral tolerance].
AB - The term oral tolerance (OT) describes the antigen-specific suppression of immune
responses following the feeding of the antigen. While some common features with
other forms of induction of systemic tolerance have been disclosed, OT can be
distinguished by certain immunologic characteristics. Thus, work in experimental
animal models revealed the importance of intestinal antigen processing,
especially antigen processing in the Peyer's patches, in inducing OT. It has
become clear that suppressive T cell cytokines derived from mucosal sites play a
major role in mediating OT. The variation of the dose of fed antigen and the
modulation of the cytokine milieu both have influences on the underlying
immunologic mechanisms active suppression, clonal anergy and clonal deletion
following oral antigen uptake. In several animal models of autoimmunity the
disease activity can be suppressed by feeding oral autoantigen. Based on these
results, recent clinical studies have begun to explore OT as a means to treat
autoimmune disorders such as multiple sclerosis, rheumatoid arthritis and
diabetes.
PMID- 10190251
TI - [Helicobacter pylori and gastric acid secretion].
AB - Helicobacter pylori (H. pylori) infection leads to profound changes in gastric
physiology. Several clinical and animal studies have been performed to clarify
the influence of H. pylori on gastric acid secretion. Published data, however,
are not consistent throughout. Infection of the gastric antrum, which can be
observed mainly in duodenal ulcer patients, increases gastrin release and
consecutively acid output. The net effect of corpus and antrum gastritis, such as
in patients with gastric cancer, is to decrease acid secretion. Chronic H. pylori
infection may finally promote gastric atrophy with irreversibly diminished acid
secretion but in earlier stages of this infection eradication of H. pylori
normalizes gastric secretory activity.
PMID- 10190252
TI - [Indirect detection of genetic mutations in colon cancers].
PMID- 10190253
TI - [Progress in the area of hepatocyte transplantation].
PMID- 10190254
TI - A full color system for quantitative assessment of histochemical and
immunohistochemical staining patterns.
AB - Quantitative measures of staining distributions are important to compare the
presence and patterns of cells or macromolecules. Typically, achromatic
thresholding systems are used to compare staining distributions. Achromatic video
signals, however, lack sufficient resolution to identify and compare chromatic
changes. The purpose of this study is to describe a full color system for
analysis of chromatic staining distributions. The hardware system includes a
Leitz Diaplan microscope, video camera, GVP videoboard and Amiga 3000 computer.
Software was developed in "C" to partition the video signal into hue (H),
saturation (S) and value (V). Also, percentage of stained area was determined.
Kodak color filters were used to assess the accuracy and precision of the system.
Craniofacial tissues were stained with varying concentrations of toluidine blue
and primary anti-BrdU antibodies. HSV and the percentage of stained areas were
determined and displayed low coefficients of error. HSV values also performed as
expected for standard filters as well as cellular staining concentrations. This
system is easily implemented and should be useful for comparing chromatic changes
with any color resulting from histochemical or immunohistochemical procedures.
PMID- 10190255
TI - Silver methenamine staining for scanning electron microscopy of bone sections
containing biomaterials.
AB - Sections of tissue containing orthopedic materials are currently used to study
the compatibility of those materials and to perform electron probe microanalysis
at the material-tissue interface. Identification of the cells in contact with the
material by Scanning electron microscopy (SEM) is of interest. We have developed
a method for staining cells and tissue structures embedded in polymethyl
methacrylate with silver methenamine once the sections have been obtained.
Sections were prepared by grinding, and the silver methenamine was applied after
oxidation with periodic acid. The procedure was carried out in a microwave oven.
Backscatter SEM showed staining of the cell nucleus membrane, chromatin, the
nuclear organizers, and the chromosomes of dividing cells. The cytoplasm and the
cytoplasmic membrane were also stained. Collagen fibers of the extracellular
matrix and the mineralized matrix of bone were labeled. Material particles in the
macrophages were easily recognizable and Energy-Dispersive Spectrometer were not
impaired by the presence of silver in the preparation.
PMID- 10190256
TI - Affixing plant sections without protein based adhesives for protease
histochemistry.
AB - To submit a section of plant tissue to histochemical analysis using protease, the
protein based adhesives which keep the slices attached to the slides must be
replaced because they are attacked by the enzyme and the slices are washed off
the slides. We devised a method to keep the slices attached to the slides during
histochemical extractions and subsequent staining. Slides are frosted on two
lateral zones by spreading on them a fluoride paste composed of 15 g barium
sulfate, 15 g ammonium difluoride, 8 g oxalic acid, 40 ml glycerine and 12 ml
deionized water using a thin paint brush. After removing the paste with tap water
and drying the slides, the sections are placed on the central clear zone of the
slide and covered with an ethyl-cellulose film that keeps the slices in place and
allows the reagents to act through it. To do this, the slides are dipped into
0.5% ethyl cellulose (ETC) prepared in a 4:1 mixture of toluene and absolute
ethanol. The ETC coating is layered three times to improve its firmness and its
ability to retain the slices on the slides. To obtain perfect adhesion, the slide
should be oven dried (40-50 C for 10-15 min) to remove any trace of humidity
before applying each layer of ETC. Subsequently the sections can be extracted and
stained without undue loss of material.
PMID- 10190257
TI - Chemical dehydration of specimens with 2,2-dimethoxypropane (DMP) for paraffin
processing of animal tissues: practical and economic advantages over dehydration
in ethanol.
AB - Chemical dehydration can be accomplished using 2,2-dimethoxypropane (DMP). In the
presence of an acid catalyst, this liquid reacts with water generating methanol
and acetone as products. Although DMP is more expensive per milliliter than
ethanol and other solvents used for dehydration, it is an economical alternative
because a much smaller volume is needed. Slow penetration of DMP was previously
thought to restrict its use to tiny specimens, but we now show that pieces of
tissue as thick as 2 cm are dehydrated by overnight immersion in acidified DMP.
We also show that dehydration in acidified DMP does not impair the staining of
RNA or other basophilic components of animal tissues. The temperature and
concentrations of methanol and H+ in the chemical dehydrating agent are too low
to produce histochemically detectable methylation or nucleic acid extraction.
PMID- 10190258
TI - Detection of experimentally produced occult microfractures at the bone-cartilage
interface in decalcified sections.
AB - We compared three histological preparation methods to detect experimentally
produced occult microfractures in decalcified human patellae: a paraffin tape
transfer technique, a paraffin slab-cut method, and a paraffin method with methyl
salicylate as the clearing agent. Microfractures were observed at the bone
cartilage interface and were oriented either parallel or perpendicular to the
tidemark. Both types of microfractures were documented with each preparation
method. The slab-cut method was time-consuming, but the section thickness allowed
detailed analysis of the architecture of microcracks as they passed into the
depth of the section. The methyl salicylate method was efficient and produced
thin, serial sections with good morphological detail and minimal cutting
artifact. Reliable histological data were also derived from the tape-transfer
technique, but this method was inconsistent. The methods summarized here for
processing decalcified human joint tissues provide a basis for future orthopaedic
studies investigating occult microfractures at the bone-cartilage interface.
PMID- 10190259
TI - Transportation and storage of cryosections in PBS-Dulbecco.
AB - Tissue pieces that cannot be fixed and embedded before immunostaining must be
cryosectioned and stained quickly. We describe an easy and reliable technique to
keep cryosections with immune complexes and complement stored for several weeks
until the final immunostaining. The same technique was used for long distance
transportation of cryosections and it was extensively tested for human kidney
biopsies with excellent results.
PMID- 10190260
TI - Improved sensitivity for high resolution in situ hybridization using resin
extraction of methyl methacrylate embedded material.
AB - An in situ hybridization procedure resulting in both high resolution and
sensitivity was established by using the removable methyl methacrylate resin,
Technovit 9100. Young bicellular pollen of tobacco (Nicotiana tabacum L. SR-1)
was embedded in Technovit 9100 resin and sectioned. The resin was extracted with
(2-methoxyethyl)-acetate followed by in situ hybridization with cRNA probes to
detect cytoplasmic 18S/25S rRNA. Signal intensity obtained by this procedure was
approximately twice as great as that obtained by an earlier procedure using
Technovit 7100, a glycol methacrylate resin that cannot be removed from sections.
This improvement in sensitivity made it possible to observe subcellular
localization of small amounts of RNA as revealed by visualization of plastid 23S
rRNA in a generative cell of Plumbago auriculata pollen.
PMID- 10190261
TI - Rapid decalcification using microwaves for in situ hybridization in skeletal
tissues.
AB - In situ hybridization histochemistry is the sole tool available for detecting the
localization and expression of specific RNA on histological sections under
various in vivo conditions. For this paper, we examined the effect of microwave
exposure on the time needed for decalcification of skeletal tissues and on the
preservation of sensitivity for hybridization signals. Our data show that the use
of microwave decalcification reduces the decalcification period while preserving
intense hybridization signals for mouse alpha1 chain of procollagen type I mRNA
in osteogenic cells in bone. The use of microwave treatment to decalcify skeletal
tissues may prevent delay in obtaining experimental results or the loss of
signals during in situ hybridization.
PMID- 10190262
TI - Management of the respiratory complications of neuromuscular diseases in the
pediatric intensive care unit.
AB - Pediatric neuromuscular diseases such as Duchenne muscular dystrophy and spinal
muscular atrophy cause pulmonary compromise. In severely affected patients, upper
respiratory tract infections exacerbate lower respiratory tract secretion
retention, with the potential for pneumonia, pulmonary atelectasis, and
respiratory failure. In the pediatric intensive care unit, effective treatment
includes noninvasive positive pressure ventilation and manual and mechanical
mucus clearance techniques. A practical approach to commonly encountered
respiratory complications in pediatric neuromuscular diseases is presented in
this review.
PMID- 10190263
TI - Neuropsychologic and adaptive functioning in adolescents and young adults shunted
for congenital hydrocephalus.
AB - The major aim of this study was to assess whether the syndrome of nonverbal
learning disabilities described in hydrocephalic children is observed in
adulthood. Eleven adults shunted for congenital hydrocephalus related to spina
bifida and eight adults shunted for hydrocephalus related to aqueductal stenosis
were administered an extensive neuropsychologic battery to investigate
discrepancies between verbal and visuospatial cognition, verbal and visuospatial
long-term memory, and psycho-social adaptive abilities. The results showed no
discrepancies between Wechsler Performance IQ or Verbal IQ in either
hydrocephalic group. Nevertheless, the subjects with spina bifida appeared more
cognitively impaired than the subjects with aqueductal stenosis, who performed
normally on the Wechsler Adult Intelligence Scale-Revised. Memory assessment
using Signoret's Memory Battery revealed no discrepancy between verbal and
visuospatial memory in the hydrocephalic group. Nevertheless, the subjects with
spina bifida had poorer verbal and visuospatial memory performance than the
subjects with aqueductal stenosis. There were no differences on the Vineland
Adaptive Behavioral Scale between subjects with spina bifida and those with
aqueductal stenosis in autonomy, socialization, and daily living skills. These
results suggest that shunted congenital hydrocephalus is not characterized by
nonverbal learning disabilities syndrome in adolescence or in adulthood.
PMID- 10190264
TI - Differing risk factors for cerebral palsy in the presence of mental retardation
and epilepsy.
AB - Whether the combined diagnosis of cerebral palsy with mental retardation or with
mental retardation and epilepsy reflects more severe manifestations of the
spectrum of cerebral palsy, or whether these conditions reflect overlapping
outcomes related to different exposure, remains an open question. At two centers,
in Rome and Conegliano, Italy, 51 children with combined cerebral palsy, mental
retardation, and epilepsy, 31 children with both cerebral palsy and mental
retardation, and 48 with cerebral palsy alone were identified and examined, and
their mothers interviewed. The triple diagnosis group was significantly more
likely than the other two groups to have a history of neonatal convulsions and a
history of epilepsy in first-degree relatives, but less likely to have a mother's
age at delivery greater than 33 years, a birthweight less than 1500 g, or
gestational age less than 32 weeks. The dual diagnosis group was more likely than
the other two groups to have maternal education of less than 8 years. These data
suggest the possibility of different etiopathogenetic pathways for various
presentations of cerebral palsy.
PMID- 10190265
TI - Infantile botulism: pitfalls in electrodiagnosis.
AB - Botulism in infants, unless recognized early, is associated with high mortality
and morbidity. The diagnosis is suspected when infants present with sudden onset
of weakness, respiratory failure, and constipation and is confirmed by
demonstration of botulinum toxin in stool several weeks later. Electrodiagnosis
allows quick and reliable confirmation of botulism. Low-amplitude compound muscle
action potentials, tetanic or post-tetanic facilitation, and the absence of post
tetanic exhaustion support the diagnosis. Two infants with confirmed botulism did
not exhibit the characteristic electrodiagnostic features, demonstrating the
pitfalls in electrodiagnosis of infantile botulism.
PMID- 10190266
TI - Association of the 677C-->T mutation on the methylenetetrahydrofolate reductase
gene in Turkish patients with neural tube defects.
AB - We report the analysis of the 677C-->T mutation on the 5, 10
methylenetetrahydrofolate reductase gene in Turkish controls and cases of neural
tube defects. Mutation analysis of 91 patients with neural tube defects, 72
mothers, 63 fathers, and 93 healthy controls has been made by polymerase chain
reaction and allele specific restriction digestion with Hinf I. We did not find a
significant difference in the 677C-->T allele and genotype distribution among the
patients with neural tube defects, their parents, and the control group. This
result suggests that another mutation in the folate-related enzyme genes could be
responsible for neural tube defects in Turkey. None of the mothers of patients
with neural tube defects was advised to use folic acid as recommended to prevent
neural tube defects. An immediate attempt to establish an education program for
healthcare providers and women of childbearing age is crucial in Turkey.
Furthermore, fortification of foods with folate would be a better approach.
PMID- 10190267
TI - Rett syndrome: randomized controlled trial of L-carnitine.
AB - Rett syndrome is a severe neurodevelopmental disorder of unknown etiology,
occurring almost exclusively in female patients. The etiology and functional
significance of plasma carnitine deficiency seen in some patients with Rett
syndrome is unknown. To investigate whether L-carnitine might be of benefit in
Rett syndrome, a randomized, placebo-controlled, double-blind crossover trial of
L-carnitine has been completed in 35 subjects. Eight-week treatment phases were
completed for both a placebo and L-carnitine. Outcome was measured by
parents/caregivers and at medical follow-up using three established tools: the
Rett Syndrome Motor Behavioral Assessment, the Hand Apraxia Scale, and the
Patient Well-Being Index. Analysis comparing change between baseline and week 8
of treatment for L-carnitine and the placebo showed that both parents/caregivers
and medical follow-up detected improvements in the subjects' well-being. In
addition, medical review showed an improvement on the Hand Apraxia Scale for a
higher proportion of girls on L-carnitine. Identification of predictors of
clinical improvement has been limited by the power of the study. These findings
suggest that L-carnitine is of benefit in some patients with Rett syndrome. While
L-carnitine did not lead to major functional changes in ability, the type of
changes reported could still have a substantial impact on the girls and their
families. Information is still needed, however, to determine if only subgroups of
girls with the disorder are responsive to L-carnitine and the appropriate
duration of therapy.
PMID- 10190268
TI - Molecular studies of Japanese patients with group A xeroderma pigmentosum using
polymerase chain reaction and restriction fragment length polymorphism and
nonradioactive single strand conformation polymorphism analyses.
AB - Xeroderma pigmentosum is an autosomal recessive disease characterized by extreme
sensitivity of the skin to ultraviolet light, which results in a high incidence
of early skin cancer. We report here the molecular analysis of the xeroderma
pigmentosum group A complementing genes of five Japanese patients with group A
xeroderma pigmentosum and their families, by polymerase chain reaction (PCR) and
restriction fragment length polymorphism (RFLP) analysis, and by PCR and non
radioactive single strand conformation polymorphism (SSCP) analysis using the
Pharmacia PhastSystem. Four of the five patients were found to be homozygous for
a known splicing mutation of intron 3. One patient was found to be heterozygous
for the splicing mutation of intron 3 and a known nonsense mutation of exon 6.
This nonradioactive PCR-SSCP technique was as useful for the molecular diagnosis
of patients with group A xeroderma pigmentosum as was PCR-RFLP analysis.
PMID- 10190269
TI - Carrell-Krusen Symposium invited lecture. Clinical trials in motor neuron
diseases.
AB - Although there is no truly effective disease-specific therapy for any of the
motor neuron diseases, rapid progress in our understanding of the pathophysiology
of some of these disorders is being made. In addition to progress in
neuroscience, clinical trials of agents that appear to slow the progress of at
least one of these diseases, amyotrophic lateral sclerosis, are beginning to show
promising results. The first clinical trials in spinal muscular atrophy are
currently underway. A number of other developments have raised the quality of
clinical trials, which should improve their productivity and efficiency in the
future.
PMID- 10190270
TI - Genetic susceptibility to neurodevelopmental disorders.
AB - A large body of evidence suggests that genetic factors influence liability to
many common neurodevelopmental disorders. Examples include Tourette syndrome,
attention-deficit hyperactivity disorder, autism, and dyslexia. Characterization
of the genetic component of susceptibility to these conditions at a molecular
level should improve classification, elucidate fundamental neurobiologic
mechanisms of disease, and suggest novel approaches to treatment. Susceptibility
loci for complex traits could be identified by detecting linkage to a well-mapped
genetic marker or by detecting association with a putative high-risk allele at a
candidate locus. This article reviews the principles underlying these
complementary approaches, and notes recent progress in specific conditions. As
the molecular epidemiology of susceptibility to common neurodevelopmental
disorders emerges, it might be increasingly possible to identify "high-risk" and
"low-risk" genotypes. Clinicians should understand the nature of this kind of
information in order to appreciate its power as well as its limitations.
PMID- 10190271
TI - Vein of Galen malformation and infantile spasms.
AB - Recently, there has been increasing interest in the study, characterization, and
management of infantile spasms. With technological advances, it is now possible
to determine a specific diagnosis on many patients with infantile spasms, thus
broadening the spectrum of conditions associated with this electroclinical
syndrome. We report a child with infantile spasms who also had a vascular
malformation of the vein of Galen. Both clinical and electroencephalographic
findings improved rapidly after endovascular treatment of the vascular anomaly,
suggesting a possible association.
PMID- 10190272
TI - Acute disseminated encephalomyelitis in childhood: report of 10 cases.
AB - We report 10 children with the diagnosis of acute disseminated encephalomyelitis.
Diagnosis was based on clinical and radiologic findings, and after acute
encephalitis was excluded by negative culture and antibody results. The most
common presenting symptom was ataxia, followed by optic neuropathy, cranial nerve
palsy, convulsions, motor dysfunction, and loss of consciousness. Brain magnetic
resonance imaging showing bilateral symmetrical hyper-intense lesions of the same
age in brain stem, subcortical white matter, thalamus, basal ganglia, or
cerebellum was the mainstay of the diagnosis. The presence of a preceding event
(either an infection or vaccination) was present in 8 of 10 patients. Brain
computed tomographic scans were abnormal in 3 of 10, and electroencephalogram was
normal in all patients. High-dose corticosteroids were given to six patients, one
received low-dose steroids, and the other three had symptomatic follow-up. Those
who relapsed were mainly from the symptomatic follow-up group. Only one patient
(the youngest) receiving high-dose methylprednisolone relapsed. Therefore, early
high-dose steroid treatment seems to be the most effective treatment in acute
disseminated encephalomyelitis and can prevent relapses.
PMID- 10190273
TI - Treatment of children with autism with intravenous immunoglobulin.
PMID- 10190274
TI - Endoproteinase-protein inhibitor interactions.
AB - Nature uses protein inhibitors as important tools to regulate the proteolytic
activity of their target proteinases. Most of these inhibitors for which 3D
structures are available are directed towards serine proteinases, interacting
with their active-sites in a substrate-like "canonical" manner via an exposed
reactive-site loop of conserved conformation. More recently, some non-canonically
binding serine proteinase inhibitors, two cysteine proteinase inhibitors, and
three zinc endopeptidase inhibitors have been characterized in the free and
complexed state, displaying novel mechanisms of inhibition with their target
proteinases. These different interaction modes are briefly discussed, with
particular emphasis on the interaction between matrix metalloproteinases (MMPs)
and their endogenous tissue inhibitors of metalloproteinases (TIMPs).
PMID- 10190275
TI - Matrix-degrading proteases and angiogenesis during development and tumor
formation.
AB - Embryonic development and tumor progression both require the exquisite
coordination of programs for extracellular matrix (ECM) formation and remodeling,
and those for angiogenesis and vascular development. Without a vascular supply
the normal tissue or tumor is limited in size and organization. Without ECM
remodeling the alteration of tissue and tumor boundaries and cellular migrations
are limited. Recent insights into the molecular mechanisms regulating the
extracellular environment of the growing embryonic tissue or tumors have
implicated proteases, the matrix metalloproteinases (MMPs) in particular, in both
the process of ECM remodeling and angiogenesis, and in a potential causal
relationship between these processes. This review focuses on the roles that MMPs
play in regulating three processes in which both proteolysis and vascular
development are tightly coordinated: embryo implantation, bone development and
tumor progression.
PMID- 10190276
TI - Meprin B: transcriptional and posttranscriptional regulation of the meprin beta
metalloproteinase subunit in human and mouse cancer cells.
AB - A novel mRNA isoform encoding the cell surface metalloproteinase meprin beta is
expressed in mouse teratocarcinoma cells and in a variety of cultured human
cancer cells. In both mouse and human cells, the cancer cell-specific mRNA
isoform, referred to as beta', has an extended 5' UTR as compared to the meprin
beta mRNA isoform expressed in normal kidney and intestinal epithelium. The work
herein aimed to determine the molecular mechanisms for the expression of meprin
beta and beta' in normal and cancer cells, respectively. Analysis of the 5' end
of the mouse meprin beta gene revealed that the unique sequences in the beta and
beta' mRNA isoforms are encoded by separate exons that are alternately spliced,
and transcribed from independent promoters. By contrast, the human meprin beta
and beta' mRNAs have identical sequences except for 87 additional bases in the 5'
UTR sequence of beta', indicating that a single, mixed usage promoter directs
expression of the isoforms. The region upstream of the human meprin beta'
transcription start site contained elements with homology to the promoters of
intestine-specific genes, interspersed with AP-1 and PEA3 elements; the latter
were essential to meprin beta' promoter activity in cancer cells. Phorbol
myristal acetate increased meprin beta' mRNA levels in cultured human colon
cancer cells, providing further evidence that AP-1/PEA3 sites are actively
involved in meprin beta' expression.
PMID- 10190277
TI - Molecular regulation, membrane association and secretion of tumor cathepsin B.
AB - Upregulation, membrane association and secretion of cathepsin B have been shown
to occur in many types of tumors and to correlate positively with their invasive
and metastatic capabilities. To further understand changes in cathepsin B
activity and localization, we have been examining its regulation at many levels
including transcription and trafficking. Our studies indicate that there may be
three promoter regions in the cathepsin B gene. Of these, continued examination
of the promoter upstream of exon 1 has indicated possible control by several
regulatory factors including E-box and Sp-1 binding elements. Upregulation of
cathepsin B at this level may account for some of the secretion of cathepsin B
found in tumors. We have also gathered evidence that endo- and exocytosis of
cathepsin B may be regulated by ras and ras-related proteins in addition to
previously described trafficking systems. There is also evidence that several
populations of lysosomes may exist and that trafficking to different populations
may determine whether cathepsin B is secreted from the tumor cell or remains
intracellular. Our results indicate that membrane association and secretion of
cathepsin B is not a random process in the tumor cell, but rather part of a
tightly controlled system.
PMID- 10190278
TI - Mechanisms for pro matrix metalloproteinase activation.
AB - The activation of pro matrix metalloproteinases (MMPs) by sequential proteolysis
of the propeptide blocking the active site cleft is regarded as one of the key
levels of regulation of these proteinases. Potential physiological mechanisms
including cell-associated plasmin generation by urokinase-like plasminogen
activator, or the action of cell surface MT1-MMPs appear to be involved in the
initiation of cascades of pro MMP activation. Gelatinase A, collagenase 3 and
gelatinase B may be activated by MT-MMP based mechanisms, as evidenced by both
biochemical and cell based studies. Hence the regulation of MT-MMPs themselves
becomes critical to the determination of MMP activity. This includes activation,
assembly at the cell surfaces as TIMP-2 complexes and subsequent inactivation by
proteolysis or TIMP inhibition.
PMID- 10190279
TI - Expression and regulation of collagenase-3 (MMP-13) in human malignant tumors.
AB - Human collagenase-3 (MMP-13) is a matrix metalloproteinase originally identified
in breast carcinomas. Recent studies have revealed that this enzyme is also
produced by a variety of malignant tumors including head and neck carcinomas,
chondrosarcomas and basal cell carcinomas of the skin. In all cases, the
expression of collagenase-3 is associated with aggressive tumors. Different
cytokines, growth factors and tumor promoters are able to up-regulate collagenase
3 expression in tumor cells or in stromal cells surrounding epithelial tumor
cells. Functional analysis of the collagenase-3 gene promoter has allowed the
identification of AP-1 and OSE-2 elements mediating, at least in part, its
expression in both normal and pathological conditions.
PMID- 10190280
TI - Regulation of cell adhesion by PAI-1.
AB - Type I plasminogen activator inhibitor (PAI-1) is the primary inhibitor of tissue
and urokinase-type plasminogen activators. It circulates in plasma complexed
with vitronectin (VN), the primary PAI-1 binding protein. The somatomedin B (SMB)
domain of VN contains both the high affinity PAI-1 binding site and the specific
site for urokinase plasminogen activator receptor (uPAR). PAI-1 is able to
regulate uPAR-mediated cell adhesion by competing with uPAR for VN binding.
Binding of PAI-1 to SMD may also affect integrin-mediated cell adhesion to VN by
hindering integrin binding to the RGD sequence adjacent to the uPAR binding site.
PMID- 10190281
TI - Human homozygous type I plasminogen deficiency and ligneous conjunctivitis.
AB - On the basis of a questionnaire sent to the ophthalmology departments of
hospitals throughout Germany, 10 patients with ligneous conjunctivitis or
pseudomembranous disease, ranging in age from 1 to 71 years were identified. All
10 patients had severely reduced plasminogen levels. Genetic analysis revealed
homozygous type I plasminogen deficiency (which had not previously been described
in humans) in 7 patients and compound heterozygous plasminogen deficiency in 1
patient. Clear differentiation was not possible in 2 patients. Most of the
parents had heterozygous plasminogen deficiency. None of the patients had
experienced any episodes of thrombosis. Additionally, the following observations
were made: 1) Levels of polymorphonuclear (PMN)-elastase protein were markedly
elevated in 6 of 6 patients and 10 of 11 parents tested, and levels were higher
in homozygotes than in heterozygotes. 2) Hereditary factor XII deficiency was
found in 3 of 6 patients tested. 3) C1-inhibitor was elevated in 2 of 4 patients,
prekallikrein was elevated in 1 of 4 patients, and plasminogen activator
inhibitor type 1 was elevated in 1 of 4 patients. Infusions of lys-plasminogen
concentrate induced pronounced fibrinolytic activity as indicated by high levels
of D-dimer, increases in plasmin-antiplasmin complex and decreases in
polymorphonuclear elastase. C1-inhibitor, prekallikrein and PAI-1 normalized
after repeated infusions of lys-plasminogen. In contrast to dysplasminogenemia,
severe type I plasminogen deficiency might be seen as a problem of extravascular
space, in particular of the mucous membranes, possibly triggered by mechanically
induced or inflammatory lesions of the vessels supplying the tissue.
PMID- 10190282
TI - Programmed cell death and the caspases.
AB - Members of a family of cysteine proteases known as caspases orchestrate the
intracellular biochemical events that enable animal cells to kill themselves by
apoptosis. To counteract the apoptotic response to infection, some viruses have
adapted and evolved proteins that specifically block caspases. More recently, it
has been demonstrated that endogenous proteins belonging to the IAP family can
regulate apoptosis by directly inactivating some of the caspases involved in
initiating and executing programmed cell death.
PMID- 10190283
TI - Proteolytic control of growth factor availability.
AB - Most growth factors are released from cells in a form that does not permit
immediate interaction with their high affinity receptors. An important mechanism
for presentation of these released latent growth factors is activation by the
plasminogen activator-plasmin system. The involvement of this system in the
biology of Transforming Growth Factor-beta (TGF-beta) is reviewed.
PMID- 10190284
TI - Cathepsin D in cancer metastasis: a protease and a ligand.
AB - Cathepsin D (cath-D) overexpression in breast cancer cells is associated with
increased risk of metastasis in patients according to several clinical studies.
No alterations of pro-cath-D structure or activation have been demonstrated in
cancer cells. However, overexpression and dysrouting of pro-cath-D in
illegitimate compartments could have consequences on tumor progression.
Transfection of a human cDNA cath-D expression vector increases the metastatic
potential of 3Y1-Ad12 embryonic rat tumorigenic cells when intravenously injected
into nude mice. The mechanism by which cath-D increases the incidence of clinical
metastasis seems to involve increased cell growth and decreased contact
inhibition rather than escape of cancer cells through the basement membrane.
Different mechanisms are discussed by which cath-D could act as a protease
following its activation or as a ligand of different membrane receptors at a more
neutral pH.
PMID- 10190285
TI - The urokinase receptor. A cell surface, regulated chemokine.
AB - Mice deficient for the urokinase plasminogen activator (uPA) gene are deficient
in the recruitment of T cells and macrophages and succumb to bacterial
infections. High levels of uPA or of its receptor (uPAR, CD87) are produced in
human cancers and are strong prognostic indicators of relapse. Thus uPA and uPAR
have a profound influence on cell migration. This set of molecules is known to
regulate surface proteolysis, cell adhesion and chemotaxis. We have investigated
the mechanism involved in uPAR-dependent chemotaxis. Chemotaxis is induced
through an uPA-dependent conformational change in uPAR which uncovers a very
potent chemotactic epitope acting through a pertussis-toxin sensitive step and
activating intracellular tyrosine kinases. The epitope is located in the linker
region between domain D1 and D2 of uPAR. Binding of uPA transforms uPAR from a
receptor for uPA into a pleiotropic ligand ("activated uPAR") for other still
unidentified surface molecules. Through these "adaptors", uPAR causes
cytoskeletal changes, activation of kinases and directional cell migration. The
conformational change can be substituted by cleavage between domain D1 and D2, in
an area that can be cleaved by uPA itself at high efficiency.
PMID- 10190286
TI - Matrilysin in early stage intestinal tumorigenesis.
AB - The demonstration that matrix metalloproteinases [MMPs] play an active role in
the invasion and metastasis stages of tumor progression has led to the
development of a new class of anti-metastatic chemotherapeutic agent, the matrix
metalloproteinase inhibitors [MMPIs]. We present evidence to suggest that the MMP
matrilysin, in particular, plays an essential role in much earlier stages of
intestinal tumorigenesis. Matrilysin is detected in a high percentage of pre
invasive lesions, in contrast to its absence in most normal tissues, and is
expressed by the epithelial-derived tumor cells. Manipulating levels of this
enzyme in vitro results in cell lines with enhanced tumorigenic potential, while
ablating the gene in vivo leads to a significant reduction in tumor number in two
different animal models of intestinal tumorigenesis. Additionally, regulation of
matrilysin gene expression appears to be under the control of genetic pathways
which are activated very early in the tumor development sequence. Although the
precise mechanism by which matrilysin activity contributes to tumor formation is
not yet clear, we propose that MMPIs may be of benefit as chemopreventative
agents in addition to their therapeutic potential for metastatic disease.
PMID- 10190287
TI - Tissue inhibitors of metalloproteinases (TIMP) in invasion and proliferation.
AB - Tissue inhibitors of matrix metalloproteinases (TIMPs) are a family of natural
inhibitors that control the activity of matrix metalloproteinases (MMPs) in the
extracellular matrix (ECM). Four members of this family have been so far
characterized in a variety of species. These inhibitors share a similar
structural feature characterized by the presence of 12 cysteine residues involved
in disulfide bonds and a similar function by their ability to form inhibitory
complexes with MMPs. The role of TIMPs in cancer has been the subject of
conflicting reports with an antitumor activity reported by some investigators and
a growth stimulation activity reported by others. Here we will discuss a series
of data obtained in our laboratory supporting a role of TIMPs not only as
inhibitors of invasion but also as regulators of cell growth. Using placental
development as an example of a regulated invasive process, we have observed that
the levels of TIMP-2 and TIMP-3 steadily increase between day 14.5 and 17.5 post
coitus. TIMPs are selectively expressed by spongiotrophoblastic cells that
separate the labyrinthine zone, rich in fetal blood vessels and maternal blood
sinuses, from the zone of giant cells forming the border between fetal and
maternal tissues. TIMPs are also potent inhibitors of tumor growth in vivo. In
melanoma cells, we have previously reported that over-expression of TIMP-2
inhibits the growth of tumors implanted in the skin of scid mice. This growth
inhibition seems independent of angiogenesis but dependent on the collagen
matrix. We observed that in the presence of fibrillar type I collagen, melanoma
cells undergo a growth arrest at the G1 to S interphase transition of the cell
cycle. This arrest is specific to the fibrillar structure of collagen because it
is not observed in the presence of non-fibrillar collagen or other ECM
components. It is associated with a specific upregulation of the cyclin inhibitor
p27KIP1. The data therefore indicate that anchorage independent cells remain
sensitive to growth regulatory signals that originate from the ECM and that these
signals can specifically block tumor cell cycle. Thus our concept of the role of
protease inhibitors such as TIMPs in cancer has substantially changed from an
initial focus on inhibition of tumor invasion and metastasis to a broader focus
on being molecules that--via their function as regulators of the ECM homeostasis-
can control tumor cell growth.
PMID- 10190288
TI - Cancer invasion and tissue remodeling--cooperation of protease systems and cell
types.
AB - Proteolytic degradation of the extracellular matrix plays a crucial role in both
cancer invasion and non-neoplastic tissue remodeling processes. In human cancers
the components of matrix degrading protease systems (uPA, uPAR, PAI-1 and MMPs)
can be expressed by either the non-neoplastic stromal cells, the cancer cells or
both. Studies of the prognostic impact of these components in human cancer and
the effect of targeted gene inactivation on cancer metastasis in mice support the
assumption that proteases promote cancer progression, independent of whether they
are expressed by cancer cells or stromal cells. The pattern of expression of
components of protease systems is usually very similar in different cases of the
same type of cancer, while it varies between different types of cancer. There are
intriguing similarities between the cellular expression pattern of components of
protease systems seen in cancer invasion and in certain types of non-neoplastic
tissue remodeling. We propose that cancer invasion can be viewed as tissue
remodeling gone out of control. The stromal cell involvement in cancer invasion
represents a new paradigm with important implications for cancer pathophysiology
and cancer therapy.
PMID- 10190290
TI - Membrane-type matrix metalloproteinases.
AB - Matrix metalloproteinases (MMP) degrade components of extracellular matrix (ECM),
and thereby regulate formation, remodeling and maintenance of tissue. Abnormal
function of cell surface proteases associated with malignant tumors may
contribute directly to the invasive and malignant nature of the cells. Among the
MMP's associated with the tumor cell surface, gelatinase A is believed to be
particularly important, since it degrades type IV collagen, and is activated in a
tumor specific manner, correlating with tumor spread and poor prognosis.
Activation of pro-gelatinase A is uniquely regulated by a cell-mediated
mechanism. This study describes an in vitro model that mimics the cell-surface
activation mechanism. The expression of MT-MMP could not be detected in normal
epithelial cells, but can be seen in transformed epithelial carcinoma cells.
PMID- 10190289
TI - An odyssey from breast to bone: multi-step control of mammary metastases and
osteolysis by matrix metalloproteinases.
AB - Development of metastases distant to the primary site of solid tumors marks late
stages of tumor progression. Almost all malignant mammary tumors are carcinomas
arising from the breast epithelium, but the morphological and molecular
alterations in the mammary stroma surrounding the premalignant and the growing
tumor contribute to its conversion into neoplastic tissue. Two parameters are
critical for initiation of the metastatic process and access of tumor cells to
the circulation. These are the ability of tumor cells to invade the basement
membrane and the stroma, and the neovascularization of breast tumor tissue. A
major site for development of distant metastases is the skeleton. After
colonizing the bone, tumor cells promote a cascade of events leading to
recruitment of osteoclasts and subsequent osteolytic bone destruction. A
ubiquitous theme of neoplastic progression of breast tumors is the overproduction
of matrix metalloproteinases. In this review, we summarize the recent insights
into the functional consequences of matrix metalloproteinase expression and
activation during malignant conversion in the breast, and after bone
colonization. The current literature supports the hypothesis that matrix
metalloproteinases play a key role in the metastatic expansion of most, if not
all, mammary tumors and in the ensuing bone loss.
PMID- 10190291
TI - Plasminogen activation in human leukemia and in normal hematopoietic cells.
AB - The active process of pericellular proteolysis is central in tumor invasion, and
in particular the essential role of the urokinase-type plasminogen activator
(uPA) is well established. uPA-mediated plasminogen activation facilitates cell
migration and invasion through extracellular matrices by dissolving connective
tissue components. uPA, its receptor (uPAR) and plasminogen activator inhibitor-1
(PAI-1) are enriched in several types of tumors. The importance of proteolysis
and especially plasminogen activation is less clear in hematopoietic malignancies
than in solid tumors. However, patients with leukemia have an increased tendency
to bleeding, not always attributable to thrombocytopenia, and tissue infiltration
by leukemic cells, processes in which plasminogen activation may be involved.
Several studies have indicated that plasminogen activators (PAs) are highly
expressed by cultured leukemia cells. Furthermore, differing from adherent tumor
cells, leukemic cells have an enhanced capacity to activate pro-uPA and mainly
the active form of uPA is released to culture medium. Ex vivo studies have shown
that uPAR, uPA and its inhibitors can be found on the surface of normal blood
cells and on the blast cell surfaces from patients with acute leukemia as well as
from plasma samples. Elevated levels of PAs and their inhibitors have been
detected in leukemic cell lysates. Few studies have tried to demonstrate a
correlation between prognosis of leukemia and levels of plasminogen activators.
More in vivo studies are needed to show, if any of the factors of the plasminogen
activation process can be used as tools in subclassification or as markers for
prognosis in leukemia. This review article will focus on the in vivo studies of
plasminogen activation in leukemia and will present several in vitro findings on
PAs in normal leukocytes and leukemic cell lines.
PMID- 10190292
TI - Clinical relevance of the urokinase plasminogen activator system in breast
cancer.
AB - Until recently clinical features and the hormone-receptor status were the only
factors used to select systemic (adjuvant) treatment for breast cancer patients.
Other biological factors are needed as well to predict the probability of relapse
and response with more certainty. The uPA-system is such a prognostic and
predictive factor in breast cancer. In this review, the results of research
groups that have related relapse-free survival to the quantitative levels of uPA
system proteins and/or activities are discussed. Only studies that described the
results from assays on cytosols or triton extracts of breast tumours were
included. The levels of uPA-system proteins help to predict the probability of
relapse and response, and knowledge of the expression levels of the various
components of the uPA-system may lead to new treatment modalities targeted on
specific properties of the uPA-system.
PMID- 10190293
TI - The urokinase plasminogen activator receptor in blood from healthy individuals
and patients with cancer.
AB - The cell surface plasminogen activation system functions in promoting tumor
dissemination, and is facilitated by a glycolipid anchored three domain receptor
for urokinase. This receptor can also be found in a soluble form (suPAR) in
extracts of tumors, as well as in plasma from both healthy individuals and cancer
patients. The suPAR in plasma consists of the intact three domain protein, but
neither the precise mechanism of its release from cell surfaces, nor its
biological function are understood. Increased levels of plasma suPAR have been
found in patients with cancers of the lung, breast, ovary, and colon, and recent
data now indicates that the level of the molecule is related to patient
prognosis.
PMID- 10190294
TI - Urokinase receptor antagonists: discovery and application to in vivo models of
tumor growth.
AB - Urokinase receptor antagonists based on the growth factor domains of both human
and murine urokinase which show sub-nanomolar affinities for their homologous
receptors have been expressed as recombinant proteins. Further modification of
these molecules by preparing fusions with the constant region of human IgG has
led to molecules with high affinities and long in vivo half-lives. Smaller
peptidic inhibitors have been obtained by a combination of bacteriophage display
and peptide analog synthesis. All of these molecules inhibit the binding of the
growth factor domain of uPA to the uPA receptor and enhance binding of the uPA
receptor to vitronectin. Protein uPA receptor antagonists were tested in an in
vivo tumor model using the human breast carcinoma MDAmb231 in immunodeficient
mice. Both human and murine receptor antagonists showed significant inhibition of
primary tumor growth, demonstrating that in vivo, both tumor and stromal cell uPA
receptor dependent plasminogen activation can modulate tumor growth.
PMID- 10190295
TI - Clinical studies with matrix metalloproteinase inhibitors.
AB - Matrix metalloproteinases (MMPs) have been implicated in the invasive growth and
spread of tumours. Potent and selective inhibitors of MMPs have been synthesized.
These inhibitors can prevent tumour invasion in vitro and have suppressed tumour
growth and metastasis in animal cancer models. Several MMP inhibitors have now
reached clinical trials. Phase I studies indicate that the inhibitors can be
given by mouth and that over the short term they are well tolerated. Longer,
randomised studies in cancer patients are now underway.
PMID- 10190296
TI - Recommendations for the reporting of soft tissue sarcoma. Association of
Directors of Anatomic and Surgical Pathology.
AB - The Association of Directors of Anatomic and Surgical Pathology has developed
recommendations for the surgical pathology reporting of common malignant tumors.
The recommendations for soft tissue sarcomas are reported herein.
PMID- 10190297
TI - Sun-exposure- and aging-dependent p53 protein accumulation results in growth
advantage for tumour cells in carcinogenesis of nonmelanocytic skin cancer.
AB - Three hundred and sixteen patients with nonmelanocytic skin cancer, including 46
cases of Bowen's disease (BOD), 134 cases of squamous cell carcinoma (SCC), and
136 cases of basal cell carcinoma (BCC), were examined immunohistochemically
using monoclonal antibody DO-7 to assess p53 protein accumulation related to sun
exposure and ageing, and growth and differentiation of skin cancer and its
precursors. The rates of p53 immunostaining of BOD, SCC and BCC were 80.4%, 76.1%
and 70.6%, respectively. p53-positive cells were present not only in cancer
nests, but also in dysplastic and even morphologically normal epidermis adjoining
cancers. Sun exposure was statistically correlated with the p53 immunostaining
scores in morphologically normal epidermis of the three skin cancers and in
cancer nests of SCC and BCC. The positivity and score of p53 protein often
differed significantly among the three types of cancer, especially in regions of
dysplasia. Interestingly, differentiation of SCC was correlated with individual
p53 scores for dysplasia and cancer nests, especially for dysplasia. BOD, as the
precursor of SCC, demonstrated the strongest p53 expression. Furthermore, 12.3%
cases with p53 negative cancer nests showed p53-positive reaction in dysplasia
and in morphologically normal epidermis. It seems that the accumulation of p53
protein plays a part in precancerous lesions and in the genesis of more highly
differentiated types of skin cancer and affects mainly the growth of tumour cells
rather than their differentiation. For BCC, however, age was significantly
related to p53 expression. Our findings suggest that overexpression of p53 in
normal skin and cancer nests of SCC and BCC is significantly related to sun
exposure, that the expression of p53 in BCC is an age-dependent process, and that
the early accumulation of p53 protein may be a useful predictor for the detection
of nonmelanocytic skin cancer.
PMID- 10190298
TI - Occurrence of ganglioside GD3 in neoplastic astrocytes. An immunocytochemical
study in humans.
AB - GD3 immunocytochemical analysis was performed in 25 human specimens obtained by
autopsy and biopsy from patients with astrocytomas, anaplastic astrocytomas,
cerebellar astrocytomas and glioblastoma multiforme (GM), using the ABC method.
Extraction of the ganglioside fraction from GM was used for thin-layer
chromatography (TLC) analysis to confirm the specificity of anti-GD3 monoclonal
antibody (DSG-1). Normal astrocytes were not immunoreactive for GD3. Neoplastic
astrocytes of low- to high-grade tumours were GD3 immunoreactive. In GM, the
multinucleated giant cells were also immunoreactive. All immunoreactivity present
was within the cytoplasm. In TLC analysis, enzyme immunostaining of gangliosides
from GM with DSG-1 showed only one positive band, which had the same TLC
migration rate as GD3, indicating that GD3 of the ganglioside fraction from GM is
the antigen detected by DSG-1. The presence of GD3 within the cytoplasm of
neoplastic astrocytes showing invasive and proliferative properties, is of
considerable interest. The implications and possible significance of the presence
of GD3 in the cytoplasm in glioma cells are discussed.
PMID- 10190299
TI - Aberrant positioning of trophoblast and lymphocytes in the feto-maternal
interface with pre-eclampsia.
AB - Pregnancy represents the growth of an allograft where fetal trophoblast cells
evade immune rejection and invade maternal tissue. There should be a balance
between fetal trophoblast and maternal immune-responsive cells and alterations in
the proportion of these cells may relate to pregnancy disorders. To test this,
the decidual tissue of placental bed biopsies was examined and trophoblast cells
and lymphocytes were quantified morphometrically; spiral arteries were classified
as unchanged, transformed or affected by acute atherosis. Normal pregnancy (n=19)
was characterized by the transformation of about one half of all spiral arteries
within the placental bed. We found that 40% of all lymphocytes were CD56+ uterine
NK cells and 60%, CD3+ T-lymphocytes; about 30% of these were CD8+ T cells.
Intrauterine growth retardation in the context of preeclampsia (n=15) was
accompanied by reduced trophoblast numbers within smaller and more tortuous
arteries and an increase in the proportion of CD56+ uterine NK cells and CD8+ T
lymphocytes in the decidua (70% of all CD3+ cells). In the case of pre-eclampsia
without fetal growth retardation (n=14) no increase in CD56+ uterine NK cells was
seen, while CD8+ T lymphocytes were significantly increased compared with the
normal level (50% of all CD3+ cells). Fetal growth retardation is associated with
poor transformation of spiral arteries and characterized by an increase of
uterine NK cells. Symptoms of pre-eclampsia are independently associated with an
increase in the cytotoxic T subset of decidual lymphocytes. Pre-eclampsia and
related fetal growth retardation are seemingly caused by an enhancement of the
maternal cytotoxic defence against the fetal allograft.
PMID- 10190300
TI - Expression of pyruvate kinase M2 in preneoplastic hepatic foci of N
nitrosomorpholine-treated rats.
AB - The expression of the pyruvate kinase (PK) isoenzymes L and M2 was analysed in
the livers of rats treated with the hepatocarcinogenic agent N-nitrosomorpholine
(NNM) in the drinking water. In control animals L-PK expression was restricted to
liver parenchymal cells, whereas M2-PK was detected in bile duct epithelial,
blood vessel wall, endothelial and Kupffer cells. In rats treated with NNM
proliferating oval cells were consistently L-PK negative and M2-PK positive,
while the ductal cells of cholangiofibroses were clearly L-PK positive and
coexpressed M2-PK. However, no morphological differentiation of ductal cells into
hepatocyte-like cells was observed. In the clear and acidophilic cell foci
storing glycogen in excess strong staining for L-PK was observed. In glycogen
poor foci induced by NNM a shift from L-PK to M2-PK expression takes place.
PMID- 10190301
TI - Epidermal participation in post-burn hypertrophic scar development.
AB - The reconstruction of epidermal architecture over time in normotrophic and
hypertrophic scars in untransplanted, spontaneously healed partial-thickness
burns has scarcely been studied, unlike the regeneration of epidermal grafts used
to cover burn wounds and the regeneration of the dermis during hypertrophic
scarring. The expression of markers of epidermal proliferation, differentiation
and activation in normotrophic and hypertrophic scars in spontaneously healed
partial-thickness burns was assessed and compared with the expression of these
markers in normal control skin of healthy persons to determine whether
hypertrophic scarring is associated with abnormalities in the phenotype of
keratinocytes. Punch biopsies were taken both of partial-thickness burns after re
epithelialisation and of matched unburned skin. At 4 and 7 months post-burn,
biopsies were taken of normotrophic and hypertrophic scars that had developed in
these wounds. The biopsies were analysed using immunostaining for markers of
keratinocyte proliferation, differentiation and activation (keratins 5, 10, 16
and 17, filaggrin, transglutaminase and CD36). We observed a higher expression of
markers for proliferation, differentiation and activation in the epidermis of
scars at 1 month post-burn than in normal control skin of healthy persons. There
was a striking difference between normotrophic and hypertrophic scars at 4 months
post-burn. Keratinocytes in hypertrophic scars displayed a higher level of
proliferation, differentiation and activation than did normotrophic scars. At 7
months post-burn all keratinocyte proliferation and differentiation markers
showed normal expression, but the activation marker CD36 remained upregulated in
both normotrophic and hypertrophic scars. Surprisingly, in matched unburned skin
of burn patients, a state of hyperactivation was observed at 1 month. Our results
suggest that keratinocytes may be involved in the pathogenesis of hypertrophic
scarring.
PMID- 10190302
TI - Myoepithelial cells and basal lamina in poorly differentiated in situ duct
carcinoma of the breast. An immunocytochemical study.
AB - A retrospective study was made of 38 selected brest tumours with a poorly
differentiated in situ duct component. These were classified on haematoxylin and
eosin (H&E) as ductal carcinoma in situ (DCIS; 10 cases), DCIS with invasion (17
cases) and DCIS with features suggestive of for stromal invasion (11 cases). The
last were these lesions composed of neoplastic ducts with irregular outlines and
a myoepithelial layer that was not clearly evident or large neoplastic ducts
growing close together or surrounded by inflammatory desmoplastic stroma. Cases
of DCIS involving areas of sclerosing adenosis were included in this category.
Consecutive sections obtained from each case were studied with a panel of
antibodies against myoepithelial cells (alpha smooth muscle actin and calponin)
and basal lamina (BL) components (laminin and type IV collagen). It was found
that in situ lesions showed well-formed basal lamina and/or an evident
myoepithelial layer. These features were lacking in the invasive areas. Nine of
the 11 cases with suggestive features of stromal invasion were reclassified as
invasive duct carcinoma (5 cases)and DCIS (4 cases), according to the absence or
presence of a continuous myoepithelial layer and/or basal lamina. In 2 such cases
immunohistochemistry yielded equivocal results and the label "suggestive of
invasion" was therefore pertinent. Immunohistochemistry facilitates the diagnosis
of breast DCIS; myoepithelial and basal lamina markers are useful in
differentiating microinvasive from in situ ductal carcinomas of the breast.
PMID- 10190303
TI - An unusual case of benign thyroid tumour consisting of epithelial and
nonepithelial components.
AB - An encapsulated tumour consisting of follicular epithelial cells, fat-laden round
cells and spindle cells was found in the right lobe of the thyroid gland of a 66
year-old woman. The follicular epithelial cells had oxyphilic cytoplasm in which
numerous mitochondria were densely packed. The fat-laden round cells were
indistinguishable from mature fat cells by light microscopy. However, they were
immunohistochemically negative for S-100 protein and epithelial markers, and
lacked a continuous basement membrane. The spindle cells embedded in the
collagenous matrix possessed well-developed rough endoplasmic reticulum, most of
which contained variably sized, non-membrane-bound lipid droplets. Bundles of
thin filaments were occasionally observed in the cytoplasm. Some spindle cells
were immunoreactive for PCNA and alpha-smooth muscle actin. There was no striking
nuclear atypia of the tumour cells and no capsular or vascular invasion by these
components. The tumour can be classified as a benign mixed tumour.
PMID- 10190304
TI - Parasitic nodule of the thyroid in a patient with Graves' disease.
AB - We report a case of a parasitic nodule of the thyroid in a patient with Graves'
disease, which mimicked a lymph node metastasis from a primary occult thyroid
carcinoma. The patient was a 67-year-old Japanese woman with a past history of
subtotal thyroidectomy for Graves' disease, who was referred to our hospital
because of a right cervical mass. A lymph node-like lesion measuring 1.5 cm in
diameter was palpable, distinct from the remnant of the right thyroid lobe.
Thyroid scintigraphy using 123I-Na revealed a hot lesion at the upper lateral
portion of the right thyroid lobe, and this was resected. Microscopically, the
mass showed thyroid follicles with lymphocytic infiltration and lymphoid
follicles. Clear ground glass nuclei, nuclear grooving and intranuclear
inclusions were not observed. No morphological evidence of the lymph node was
found in the mass by reticulin staining. Parasitic nodules of the thyroid in
patients with Graves' disease may mimic a metastatic carcinoma of the thyroid.
PMID- 10190305
TI - Utility of immunophenotypic and immunogenotypic analysis in the study of necrotic
lymph nodes.
AB - We report a case of complete lymph node necrosis. No specific aetiology could be
determined by morphology, but a B lymphoid population and clonal rearrangement of
the immunoglobulin heavy chain gene were demonstrated in immunophenotypic and
immunogenotypic studies performed using DNA extracted from paraffin embedded
necrotic tissue. In the setting of lymph node necrosis, we suggest that
immunohistochemical and gene rearrangement studies may provide additional
diagnostic information.
PMID- 10190306
TI - Systemic granulomatous arteritis associated with Epstein-Barr virus infection.
AB - A 61-year-old woman initially presented with symptoms and findings reminiscent of
infectious mononucleosis, and her illness then took a rapidly fatal course.
Autopsy revealed widespread granulomatous arteritis, with multinucleated giant
cells but without eosinophils and fibrinoid necrosis, affecting small arteries
and arterioles and infiltration of haemophagocytic histiocytes into many organs.
In situ hybridization with Epstein-Barr virus (EBV)-specific oligonucleotide
probes showed positive signals in the infiltrating immune cells and epithelial
and endothelial cells of the affected organs. EBV-associated haemophagocytic
syndrome (EBV-AHS) with systemic granulomatous arteritis was diagnosed. From the
immunophenotypes of the infiltrating immune cells, a possible role of CD4+ T
cells in the pathogenesis of this haemophagocytic syndrome and granulomatous
vasculitis was suggested.
PMID- 10190307
TI - ABL amplification in a patient with lymphoid blast crisis of chronic myelogenous
leukaemia.
AB - Although chronic phase myelogenous leukaemia (CML) is characterised by the
Philadelphia (Ph) chromosome leading to a fusion of the BCR and ABL genes,
additional genetic alterations involved in blast crisis are poorly understood. We
report an at least 15-fold amplification of the ABL oncogene in a 29-year-old
male patient with a variant Ph-positive t(19;22)(p13;q11.2) CML who presented in
lymphoid blast crisis. Our finding suggests that an amplification of the ABL
oncogene might play a part in the appearance of an aggressive phenotype in some
cases of CML.
PMID- 10190308
TI - Simultaneous occurrence of Hodgkin's disease, nodal Langerhans' cell
histiocytosis and multiple myeloma IgA(kappa).
AB - A 35-year-old man suffered simultaneously from nodular sclerosis Hodgkin's
disease (HD), Langerhans' cell histiocytosis and multiple myeloma (MM). There was
no prior history of irradiation or chemotherapy, and clinically the lymphoma was
confined to cervical lymph nodes. Immunohistochemically, neoplastic lymphoma
cells reacted with CD15 and CD30 markers. The patient's bone marrow exhibited a
diffuse infiltration by rather atypical plasma cells showing kappa immunoglobulin
light-chain restriction. At 14 months after the diagnosis, after autologous bone
marrow transplantation, the clinical evolution is favourable with complete
remission of the diseases. This is the first time that the coexistence of these
three haematological disorders has been discussed, and only the fourth documented
case of simultaneous HD and MM. Speculations about the significance of this
finding are discussed.
PMID- 10190309
TI - Epithelial mesothelioma with deciduoid features.
AB - A rare case of malignant mesothelioma in a 15-year-old girl is described. The
patient presented with secondary amenorrhoea and clinical symptoms resembling
those of an ovarian cyst. One large and multiple small peritoneal nodules were
found at laparoscopy. Histologically the tumour was characterised by an unusual
pattern with a superficial resemblance to decidual reaction, but because of
significant mitotic activity the diagnosis of a malignant tumour, epithelial
mesothelioma with deciduoid features, was made. The patient died 11 months after
diagnosis. Post-mortem examination revealed extensive extraperitoneal spread.
PMID- 10190310
TI - Autonomic nerve tumour with skeinoid fibres: ultrastructure of skeinoid fibres
examined by quick-freezing and deep-etching method.
AB - A case of gastrointestinal autonomic nerve tumour with skeinoid fibres (SFs) of
the jejunum in a 79-year-old Japanese man, was examined by the quick-freezing and
deep-etching (QF-DE) method. The tumour consisted of spindle cells with
immunohistochemical reactions for vimentin, NSE and CD34. Electron
microscopically, features of the neural cells of the myenteric plexus were
observed. The QF-DE method demonstrated intercellular meshwork structures,
consisting of thin filaments (7-15 nm), with granular deposits. Fully developed
parts of the deposits formed nodular aggregates composed of irregularly surfaced
thick fibrils (30-48 nm) with a tendency to linear arrangement (SFs). We detected
many interconnecting thin filaments (ICTFs) between the SFs, which were pre
existing components in the meshwork, avoiding the granular deposits. The focal
thickening formed by the connection between SFs and ICTFs revealed a periodicity
typical of SFs (33-45 nm). We conclude that SFs are formed by decoration of the
granular deposits along pre-existing intercellular meshwork structures.
PMID- 10190311
TI - Amplification and overexpression of the cyclin D1 and epidermal growth factor
receptor genes in non-small-cell lung cancer. Lung Cancer Study Group.
AB - PURPOSE: To study the structure and expression of the cyclin D1 and the epidermal
growth factor receptor (EGFR) genes in a cohort of 298 non-small-cell lung cancer
(NSCLC) specimens. METHODS: Gene structure was studied by Southern analysis, and
gene expression was studied by Northern analysis and immunohistochemical
analysis. RESULTS: Amplification of the cyclin D1 locus was found in 14/298 (5%)
specimens. All 12/12 specimens with amplification of the cyclin D1 gene for which
RNA was available were found to express the cyclin D1 transcript, and 11/12
overexpressed the transcript to levels higher than that of uninvolved lung. The
EGFR gene was amplified in 17/286 samples of NSCLC tested, and was overexpressed
in 22/169 (13%) cases tested, including 12/13 cases with amplification of the
gene for which RNA was available. Cyclin D1 gene amplification was associated
with advanced lymph node involvement (P = 0.043), but not with larger tumor size
or adverse outcome. Cyclin D1 gene amplification and overexpression occurred
independently of retinoblastoma tumor-suppressor gene (RB) inactivation, but
tumors with amplification of the cyclin D1 gene were more likely to have EGFR
gene amplification (P < 0.005). No correlation of EGFR gene amplification or
overexpression with tumor size, lymph node involvement, patient demographic data,
or survival was identified. CONCLUSIONS: These data indicate that the cyclin D1
and EGFR genes are amplified and overexpressed in NSCLC, and amplification of the
cyclin D1 gene occurs frequently in conjunction with amplification of the EGFR
gene.
PMID- 10190312
TI - Differential expression of mucins and trefoil peptides in native epithelium,
Barrett's metaplasia and squamous cell carcinoma of the oesophagus.
AB - BACKGROUND AND AIMS: In humans, trefoil peptides (TFF peptides) and some mucins
have been reported to be expressed in a cell-specific manner at mucosal surfaces
of normal gastrointestinal tissues. Neoplastic conditions cause characteristic
changes of these expression patterns. To study such patterns in Barrett's
metaplasia and squamous cell carcinoma of the oesophagus (SCC), the distribution
of MUC1, MUC2, MUC5AC and the three TFF peptides (TFF1, TFF2 and TFF3) was
investigated. METHODS: In 40 archival samples of SCC and in 21 samples of
Barret's metaplasia, expression of the three mucins and two TFF peptides (TFF1
and TFF2) was assessed by specific antibodies. Reverse transcriptase/polymerase
chain reaction amplification (RT-PCR) was performed on frozen tissue samples from
the 11 biopsies of SCC for the three TFF peptides. RESULTS: Immunohistochemical
tests for MUC2 and TFF2 were negative both in samples of Barret's metaplasia and
in SCC. MUC1 expression was detected in 57.5% of the tumour samples, while TFF1
and MUC5AC were found in 10% and 7.5% of the cases respectively. In Barrett's
metaplasia MUC1 was detected in 90.5% of the cases and TFF1 and MUC5AC in all of
them. RT-PCR analysis revealed a more complex pattern: TFF1 and TFF3 expressed
the corresponding mRNA in all samples investigated; the third member, TFF2, was
active in 45.5% of the carcinoma biopsies and not in the corresponding native
tissue. CONCLUSIONS: This finding in oesophageal carcinoma contrasts with the
situation found in normal and neoplastic stomach epithelium where TFF1 and TFF2
are found co-expressed and TFF3 remains silent. Interestingly, MUC1 is expressed
in a significant proportion of SCC. Both in Barett's metaplasia and in SCC the
expression of MUC5AC mirrors the TFF1 synthesis in intensity and spatial
distribution.
PMID- 10190313
TI - The targeted expression of the human interleukin-2/interferon alpha2b fused gene
in alpha-fetoprotein-expressing hepatocellular carcinoma cells.
AB - This study explores the use of a liver-specific albumin promoter and a tumor
specific alpha-fetoprotein (AFP) enhancer to achieve the regulated expression of
the cytokine interleukin-2/interferon alpha2b (IL-2/IFNalpha2b) fused gene for
treatment of hepatocellular carcinoma (HCC). The human AFP enhancer (E(AFP)) and
albumin promoter (P(ALB)) were amplified from human chromosome DNA by the
polymerase chain reaction. A recombinant retrovirus was constructed including, as
a selectable marker, the neoR gene and the IL-2/IFNalpha2b fused gene controlled
by E(AFP)-P(ALB). The liver-targeted expression pattern of the IL-2/IFNalpha2b
fused gene was observed when this product was tested in the culture medium of the
infected cells (IL-2 activity was 850 IU/10(6) cells, IFNalpha activity was 320
IU/10(6) cells). Moreover, The growth of the IL-2/IFNalpha2b-fused-gene-infected
HCC cells, SMMC7721, was clearly suppressed by the second week after innoculation
of nude mice compared to the control SMMC7721 cells infected with LXSN and
untreated SMMC7721 cells (0.5 +/- 0.1 cm versus 1.4 +/- 0.2 cm and 1.6 +/- 0.2
cm, P < 0.05). The results showed that the combined transcriptional regulatory
sequences of E(AFP)-P(ALB) could control the targeted expression of cytokine
genes in AFP-positive human HCC cells, and the expression level of the IL
2/IFNalpha2b fused gene was positively correlated to the level of AFP expression
in the infected cells. The IL-2/IFNalpha2b fused protein that was expressed has
the functions of both IL-2 and IFNalpha. Therefore, this study illustrates the
superiority of using transcriptionally targeted recombinant retrovirus vectors in
cytokine-based gene therapy.
PMID- 10190315
TI - Reduction of transglutaminase 2 expression is associated with an induction of
drug sensitivity in the PC-14 human lung cancer cell line.
AB - Recently a role for transglutaminase 2 (TGase 2) in the drug resistance of cancer
cells has been suggested, although the mechanism is unclear. In the present
study, we observed that doxorubicin-resistant PC-14/ADR cells showed a ten-fold
higher level of TGase 2 expression than drug-sensitive PC-14 cells. PC-14/ADR
cells exhibited the classical multidrug resistance (MDR) phenotype, which was
cross-resistant to vincristine, but not to cisplatin. The stepwise induction of
resistance to doxorubicin and vincristine in PC-14 cells was accompanied by a
gradual increase of TGase 2 expression, but this expression was not increased
with induction of cisplatin resistance. To confirm the role of TGase 2 protein in
the acquisition of drug resistance in PC-14 cells, the TGase 2 expression in PC
14/ADR cells was reduced by stable transfection with the antisense or ribozyme
construct. In the clones showing reduced expression of TGase 2, lactate
dehydrogenase released from drug-treated cells was increased in the presence of
either MDR-related drugs (doxorubicin and vincristine) or a non-MDR-related drug
(cisplatin). These data suggest that TGase 2 can play a role in the acquisition
of drug resistance in PC-14 cells through a general cellular defense system other
than the MDR-related system.
PMID- 10190314
TI - Decreased expression of the peroxisomal bifunctional enzyme and carbonyl
reductase in human hepatocellular carcinomas.
AB - Human hepatocellular carcinomas (HCC) are known to frequently exhibit clear-cell
or fatty change. The expression of three enzymes related to fatty acid
metabolism, the peroxisomal bifunctional enzyme (enoyl-CoA hydratase/3
hydroxyacyl-CoA dehydrogenase, BE), cytosolic carbonyl reductase (CR) and the
alpha-class glutathione S-transferase (GST) was investigated
immunohistochemically in 45 HCC samples, to examine their relevance to this
phenomenon and to antioxidant cellular defence. The tumour sizes ranged from 3 mm
to 37 mm in diameter (mean 19 mm). Of 8 highly differentiated carcinomas
(Edmondson's grade 1), 5 and 6 showed positive staining for BE and CR
respectively, like the surrounding non-hepatoma tissues. Of 37 Edmondson's grade
II-IV lesions, 31 exhibited negative or only weakly positive staining for both
enzymes, as compared with the surrounding tissues. The combined rates for weakly
positive and negative staining for BE or CR were proportional to the degree of
dedifferentiation. However, 3 of 26 grade III tumours showed enhanced staining.
Intensities of staining for CR were in accordance with those for BE in 40 of the
total of 45 HCC. Immunoblot analysis also demonstrated concerted alteration of
the two enzymes in carcinoma tissues. The staining of the alpha-class GST was
hardly changed in Edmondson's grade I and II cases but was decreased in 24 of 31
grade III and IV lesions. The great majority of the BE-negative carcinomas did
not demonstrate fatty or clear-cell change. These results suggested that BE and
CR might be possible markers for the analysis of multistage hepatocarcinogenesis
but that decrease or loss was not reflected in increased fat storage.
PMID- 10190316
TI - Prognostic significance of c-erbB-2 protein expression in carcinoma of the cervix
treated with radiotherapy.
AB - PURPOSE: The relationship was studied between c-erbB-2 expression and outcome in
107 carcinomas of the cervix treated with radical radiotherapy. METHODS: Formalin
fixed, paraffin-embedded sections were stained by immunohistochemistry for over
expression of the c-erbB-2 protein. A retrospective study of treatment outcome
was made on patients with a median follow-up of 55 months. RESULTS: Patients with
c-erbB-2-positive tumours had a significantly worse overall survival rate than
those with c-crbB-2-negative tumours (P=0.019). Metastasis-free survival (i.e.
recurrence outside the radiotherapy field) was also significantly worse (P <
0.001) but there were no differences in local control (i.e. recurrence within the
radiotherapy field) rates (P=0.24). Bivariate log-rank analyses showed that the
prognostic value of c-erbB-2 expression for metastasis-free survival was
independent of disease stage, histological grade, patient age, tumour size and
tumour radiosensitivity. A combination of two biological parameters yielded a
high discrimination between outcome groups. Women with radiosensitive and c-erbB
2-negative tumours had a 5-year metastasis-free survival level of 70% compared to
33% for women with radioresistant, c-erbB-2-positive tumours. CONCLUSIONS: c-erbB
2 expression is an important prognostic factor for determining tumour recurrence
outside the treatment field in cervix carcinomas treated with radiotherapy.
PMID- 10190317
TI - A phase II trial of dose-intensive interleukin-2 in metastatic renal cell
carcinoma.
AB - PURPOSE: High-dose bolus interleukin-2 (IL-2) is currently the sole agent
approved by the Food and Drug Administration for the treatment of advanced renal
cell carcinoma. This phase II study was designed to evaluate the clinical
activity and toxicity spectrum of a regime consisting of dose-intensive IL-2 in
both previously treated and untreated patients with advanced renal cell
carcinoma. PATIENTS AND METHODS: Twenty eligible, sequential patients received IL
2 at a dose of 24 mlU m(-2) dose(-1) (1.33 mg m(-2) dose(-1)) every 8 h on days 1
5 and 15 19, for a maximum of 28 boluses. Patients achieving stable disease or a
response were treated every 10 weeks for a maximum of five cycles/year. RESULTS:
Out of 20 study participants 8 patients (40%; 95% confidence interval, 18.5%
61.4%) demonstrated a response. Three of these responses were complete (CR; 15%)
while 5 were partial (PR; 25%) and about 75% of the responses occurred in
patients with extensive tumor burdens. All 3 CR continue to respond after 28+ to
30+ months. With a median follow-up time of 26 months, the median overall
survival duration for all patients is 18.0 months (95% confidence interval 12-24
months). Response was observed to correlate significantly with the IL-2 dose
intensity. A dose intensity below 1440 mlU m(-2) year(-1) and at least 1440 mlU
m(-2) year(-1) correlated highly with failure to achieve CR and the successful
achieving of CR respectively (P < 0.01). An analysis of the present study
database in the context of five previous similar trials demonstrated a
significant correlation between IL-2 dose intensity and response rate by
regression analysis (r=0.89; P < 0.019). Finally, all toxicities were reversible
once the dosing had concluded. CONCLUSIONS: IL-2 dose intensity appears to
represent a significant determinant of successful clinical outcomes. This dose
intensive approach led to a high proportion of durable responses. Further
evaluation of this regimen is warranted.
PMID- 10190318
TI - Trends in survival of patients with ovarian cancer in Saarland, Germany, 1976
1995.
AB - PURPOSE: We aimed to monitor recent progress in survival of patients with ovarian
cancer. METHODS: We assessed trends in survival in 1976-1995 among patients
notified to the population-based cancer registry of Saarland, Germany, with a
first diagnosis of ovarian cancer below the age of 80 years. A new statistical
methodology was applied that allows the most timely detection of changes in
survival rates. RESULTS: There was a dramatic, ongoing increase in 5-year
relative survival rates from 36.6% in 1976-1980 to 60.1% in 1991-1995 among
patients whose cancer was detected below the age of 55 years, and from 23.7% to
42.9% in patients aged 55-64 years at the time of diagnosis. No such improvement
was seen among older patients, who continued to have a very poor prognosis.
Therefore, the variation of prognosis with age was strongly increasing over time.
CONCLUSIONS: Improvement of prognosis in younger patients most likely reflects
the benefits of more aggressive surgery and chemotherapy in these age groups.
Efforts should be made to overcome obstacles to more successful therapy for older
patients.
PMID- 10190319
TI - Quality in psychosocial oncology: Third Psychosocial Cancer Conference 1-4 April
1998, Heidelberg, Germany.
PMID- 10190320
TI - Interferon alpha2b differentially affects proliferation of two human renal cell
carcinoma cell lines differing in the P-glycoprotein-associated multidrug
resistant phenotype.
AB - PURPOSE: Interferon alpha (IFNalpha) has been used in the immunotherapy of renal
cell carcinoma (RCC), but the various mechanisms of its antiproliferative effects
are poorly understood. Recent evidence suggests that IFNalpha is involved in the
up-regulation of multidrug resistance (MDR) gene expression, and that the MDR
gene product, P-glycoprotein (Pgp). facilitates the transport of several
cytokines, some of which have been implicated in mediating tumor
antiproliferative effects. We hypothesized that IFNalpha-induced
antiproliferative activity may require Pgp-mediated transport, and that
susceptibility to IFNalpha may thus correlate with Pgp expression. METHODS: Pgp
expression by the human RCC cell lines KTCTL-2 and KTCTL-26 was characterized by
immunofluorescence staining, using the Pgp-specific primary antibodies C219 and
JSB1. KTCTL-2 and KTCTL-26 cell lines were subsequently treated with IFNalpha2b,
and growth kinetics of treated and control cell cultures were determined daily by
cell counting. RESULTS: KTCTL-2 expresses Pgp at low levels, whereas KTCTL-26 is
a highly expressing cell line. IFNalpha2b treatment abrogated cell proliferation
in KTCTL-26, whereas proliferation of KTCTL-2 was only partially inhibited.
CONCLUSIONS: We have identified two RCC cell lines that differ in the MDR
phenotype and exhibit different responses to the antiproliferative activity of
IFNalpha2b. These preliminary findings raise the possibility that susceptibility
to the antiproliferative effects of IFNalpha2b may correlate with Pgp expression,
and further studies are warranted.
PMID- 10190321
TI - Contribution of gene conversion in the evolution of the human beta-like globin
gene family.
AB - Gene conversion is referred to as one of two types of mechanisms known to act on
gene families, mainly to maintain their sequence homogeneity or, in certain
cases, to produce sequence diversity. The concept of gene conversion was
established 20 years ago by researchers working with fungi. A few years later,
gene conversion was also observed in the human genome, i.e. the gamma-globin
locus. The aim of this article is to emphasize the role of genetic recombination,
particularly of gene conversion, in the evolution of the human beta-like globin
genes and further to summarize its contribution to the convergent evolution of
the fetal globin genes. Finally, this article attempts to re-examine the origin
and spread of specific mutations of the beta-globin cluster, such as the sickle
cell or beta-thalassemia mutations, on the basis of repeated gene conversion
events.
PMID- 10190322
TI - World distribution of the T833C/844INS68 CBS in cis double mutation: a reliable
anthropological marker.
AB - Mild hyperhomocysteinemia is associated to mutations either in cystathionine beta
synthase (CBS) or in 5,10-methylenetetrahydrofolate reductase (MTHFR) genes. In
1995, Sebastio et al. characterized a 68 bp insertion in cis with the most common
CBS mutation (T833C) detected in homocystinuric patients. Recently, this double
mutation has been detected in Italian and North-American controls. Compared to a
group of patients affected by coronary artery disease, North-American controls
showed not statistically significant difference. Moreover, Italian controls
displayed a microheterogeneity in the mutant allele frequency distribution
depending on their geographical origin (North or South of Italy). Aim of our
study was to evaluate the prevalence of the double in cis mutation in different
populations. We studied 377 healthy subjects belonging to various human groups.
Genomic DNA, extracted from peripheral blood samples, was amplified using
specific primers; PCR fragments were digested with Bsr I restriction enzyme to
detect the double mutation. Our data show a significant heterogeneity among the
populations studied, therefore this mutation turned out to be a reliable
anthropogenetic marker. The distribution of the double mutation will contribute,
with other DNA polymorphisms, to evaluate the genetic admixture of mixed
populations such as Afro-Americans.
PMID- 10190323
TI - Genomic structure, promoter characterisation and mutational analysis of the
S100A7 gene: exclusion of a candidate for familial psoriasis susceptibility.
AB - We have recently assigned a locus for familial psoriasis (PS) susceptibility to
the region containing the epidermal differentiation complex gene cluster on
chromosome 1q21. Gene S10OA7 maps within this cluster and is reported to be
markedly over-expressed in the skin lesions of psoriatic patients. In order to
analyse S100A7 as a candidate for PS susceptibility, we have determined its
genomic structure regarding exon-intron boundaries and the transcription start
site. The gene is organised in three exons and two introns, spanning 2.7 kb. The
5' flanking region contains AP1- and Sp1-binding motifs and a TATA box. We have
performed functional assays by using the beta-galactosidase gene as a reporter
and have confirmed that this region has strong promoter activity. To search for
nucleotide variation within S100A7, we have designed a set of primers to amplify
each exon and the gene promoter. Polymerase chain reaction products from 15
unrelated PS patients selected from 1q-linked pedigrees and 25 normal controls
have been characterised by single-strand conformation polymorphism and direct
sequencing techniques. These analyses have revealed the presence of two
polymorphisms in the promoter region (-559G/A and -563 A/G), neither of which
shows preferential association with the disease. Our results indicate that S100A7
can be excluded as a candidate for PS susceptibility.
PMID- 10190325
TI - Identification and characterization of mutations in patients with holocarboxylase
synthetase deficiency.
AB - Holocarboxylase synthetase deficiency (HCS) is an autosomal recessive disorder
characterized by metabolic ketoacidosis, abnormal urine organic metabolites, and
dermatitis. These symptoms are improved by pharmacological doses of biotin. In
this study, we have analyzed seven patients with HCS deficiency found in European
and Middle Eastern countries by using reverse transcription/polymerase chain
reaction/single-stranded conformation polymorphism and a sequencing analysis.
Although we had previously reported that two mutations were frequent in Japanese
patients, no frequent mutations were found in the patients analyzed in this
study. Seven novel mutations were identified in the cDNA of the patients; these
included three missense mutations, two single-base deletions that resulted in a
termination codon, a three-base in-frame deletion, and a 68-bp deletion. A new
polymorphism C1121T was also identified in four alleles. A transient expression
study demonstrated that the HCS activities of three missense mutations and one
amino acid deletion were 1%-14% that of wild-type cDNA; in contrast, the
activities of the two single-base deletions followed by a termination codon and
Asp571Asn were nearly undetectable. These data suggest that a variety of
mutations is responsible for decreasing HCS activity and that the aspartate
residue at amino acid position 571 may be crucial for the catalytic activity of
HCS.
PMID- 10190324
TI - Supravalvular aortic stenosis: a splice site mutation within the elastin gene
results in reduced expression of two aberrantly spliced transcripts.
AB - We have screened the elastin gene for mutations responsible for supravalvular
aortic stenosis (SVAS) in two large, independently collected families with
isolated (nonsyndromic) SVAS. By single-strand conformation polymorphism and
heteroduplex analysis, we have identified a C to G transversion within the
acceptor splice site of exon 16 in SVAS patients from both families. This
mutation segregates in both families with high penetrance of SVAS, and all
affected individuals carry the mutation. Haplotype analysis by using closely
linked polymorphisms, including a previously unreported BfaI restriction fragment
length polymorphism within the 3'-UTR of the elastin gene, indicates that the
mutations found in the two apparently non-overlapping kindreds are identical by
descent. To study the effect of the mutation on the expression of the mutant
allele, we have established a primary skin fibroblast culture from one of the
affected individuals. Reverse transcription/polymerase chain reaction analysis of
elastin mRNA species indicates that the mutation results in two abnormal elastin
mRNA species. One mutant elastin mRNA is generated by the activation of a cryptic
splice site that lies within intron 15 and that adds 44 bp of intronic sequence
to the sequence encoded by exon 16. This insertion creates a frame shift that
results in a 59-amino-acid-long abnormal protein sequence and leads to a
termination codon in the mRNA sequence encoded by exon 17. The smaller abnormal
mRNA species arises as a consequence of the skipping of exon 16. This study
demonstrates, for the first time, the expression of mutant alleles of the elastin
gene in patients with isolated SVAS.
PMID- 10190326
TI - Estimating European admixture in African Americans by using microsatellites and a
microsatellite haplotype (CD4/Alu).
AB - We have analyzed 10 unlinked microsatellites and a linked Alu deletion
polymorphism at the CD4 locus in an African American population sample from
Chicago (USA). Heterozygosity estimates at the microsatellite loci range from
0.727+/-0.025 (D3S1358) to 0.873+/-0.017 (D18S51), with an average of 0.794+/
0.016. These values are comparable to or higher than those reported for
Europeans, with only one exception (D3S1358). The CD4/Alu haplotypic diversity
(0.887+/-0.012) is comparable to diversity levels observed in sub-Saharan African
populations and is higher than the diversity levels reported in European
populations. No consistent pattern of within, between, or multi-locus deviations
from Hardy-Weinberg expectations is observed, suggesting a low sub-heterogeneity
within the sampled population. We have applied a maximum likelihood method and
estimated the proportion of European admixture to the African American gene pool
to be 0.26+/-0.02. The narrow confidence interval indicates that allele frequency
data from multiple microsatellite loci, whether analyzed independently or as
haplotypes, are particularly useful for estimating genetic admixture.
PMID- 10190327
TI - Further evidence for a synergistic association between APOE epsilon4 and BCHE-K
in confirmed Alzheimer's disease.
AB - Recent reports on a potential association between the K-variant of the gene for
butyrylcholinesterase (BCHE-K) and Alzheimer's disease (AD) are discordant. An
initial finding of association through a synergistic enhancement of risk of APOE
epsilon4 with late-onset AD has not been confirmed by others. We have conducted a
case-control study of histopathologically confirmed AD (n=135) and non-AD (n=70)
cases (age of death > or =60 years), in which we have genotyped for APOE
epsilon4, BCHE-K, and BCHE-A1914G, a silent polymorphism 299 bp downstream of the
BCHE-K mutation. The allelic frequency of BCHE-K was 0.13 in the controls and
0.23 in the AD cases, giving a carrier odds ratio (OR(c)) of 2.1 (95% C.I. 1.1
4.1) for BCHE-K in confirmed AD. The allelic frequency for the BCHE-1914G variant
was 0.19 and 0.33 in controls and AD cases, respectively (OR(c)=2.4; 95% C.I. 1.3
4.5). In an older sub-sample of 27/70 controls and 89/135 AD patients with ages
of death > or =75 years, the OR(c) was increased to 4.5 (95% C.I. 1.4-15) for
BCHE-K and 2.7 (95% C.I. 1.0-7.2) for BCHE-1914G carriers. The BCHE-K association
with AD became even stronger in carriers of at least one APOE epsilon4 allele.
Only three out of 19 controls compared with 39/81 AD cases carried BCHE-K in
addition to APOE epsilon4, giving an odds ratio of confirmed AD of 5.0 (95% C.I.
1.3-19) for BCHE-K carriers within APOE epsilon4 carriers. Five out of 19
controls and 52/81 AD cases carried BCHE-1914G, giving the same odds ratio of
confirmed AD of 5.0 (95% C.I. 1.6-16) for BCHE-1914G carriers within APOE
epsilon4 carriers. In addition, our results suggest strong linkage disequilibrium
between BCHE-K and BCHE-1914G but no major association of the sole BCHE-1914G
chromosome with AD. We conclude that BCHE through its K-variant, rather than a
nearby marker, is a susceptibility factor for AD and enhances the AD risk defined
by APOE epsilon4 alone in an age-dependent manner.
PMID- 10190328
TI - Amplification of Y-chromosomal STRs from ancient skeletal material.
AB - The adaptation to ancient DNA analysis of a Y-chromosomal STR (short tandem
repeat) multiplex comprising the four STR systems DYS19, DYS390, and DYS389I/II
shows the suitability of Y-chromosomal STR typing on ancient human remains. A new
primer site for the system, DYS389I/II, resulting in products shortened by 94 bp,
was chosen to serve the special needs of amplification of ancient DNA. For the
first time, it was possible to amplify STR loci of the Y chromosome from
historical and prehistorical bones of up to 3000 years old.
PMID- 10190329
TI - Family history characteristics, tumor microsatellite instability and germline
MSH2 and MLH1 mutations in hereditary colorectal cancer.
AB - Recent characterization of the molecular genetic basis of hereditary nonpolyposis
colorectal cancer provides an important opportunity for identification of
individuals and their families with germline mutations in mismatch repair genes.
Cancer family history criteria that accurately define hereditary colorectal
cancer are necessary for cost-effective testing for germline mutations in
mismatch repair genes. The present report describes the results of analysis of 33
colorectal cancer cases/families that satisfy our modified family history
criteria (Mount Sinai criteria) for colorectal cancer. Fourteen of these families
met the more stringent Amsterdam criteria. Germline MSH2 and MLH1 mutations were
identified by the reverse transcription-polymerase chain reaction and the protein
truncation test, and confirmed by sequencing. Microsatellite instability analysis
was performed on available tumors from affected patients. MSH2 or MLH1 mutations
were detected in 8 of 14 Amsterdam criteria families and in 5 of the remaining 19
cases/families that only satisfied the Mount Sinai criteria. Three of the latter
families had features of the Muir-Torre syndrome. A high level of microsatellite
instability (MSI-H) was detected in almost all (16/18) colorectal cancers from
individuals with MSH2 and MLH1 mutations, and infrequently (1/21) in colorectal
cancer specimens from cases without detectable mutations. Families with germline
MSH2 and MLH1 mutations tended to have individuals affected at younger ages and
with multiple tumors. The Amsterdam criteria are useful, but not sufficient, for
detecting hereditary colorectal cancer families with germline MSH2 and MLH1
mutations, since a proportion of cases and families with mutations in mismatch
repair genes will be missed. Further development of cancer family history
criteria are needed, using unbiased prospectively collected cases, to define more
accurately those who will benefit from MSH2 and MLH1 mutation analysis.
PMID- 10190331
TI - Non-syndromic hearing loss associated with enlarged vestibular aqueduct is caused
by PDS mutations.
AB - Enlarged vestibular aqueduct (EVA), known as the most common form of inner ear
abnormality, has recently been of particular genetic interest because this
anomaly is inherited in a recessive manner. The locus for non-syndromic
sensorineural hearing loss with EVA has been mapped to the same chromosomal
region, 7q31, as the Pendred syndrome locus. In the present study, seven
mutations in the PDS gene (PDS), the gene responsible for Pendred syndrome, have
been found in families of non-syndromic sensorineural hearing loss with EVA. One
family is homozygous, three families are compound heterozygotes, and two families
are heterozygous but with no other mutation detected. The present results provide
evidence that mutations in PDS cause both syndromic and non-syndromic hearing
loss.
PMID- 10190330
TI - Nucleotide sequence diversity in non-coding regions of ALDH2 as revealed by
restriction enzyme and SSCP analysis.
AB - The simultaneous analysis of closely linked nucleotide substitutions has recently
become possible. However, it is not known whether the construction of molecular
haplotypes will be a generally useful strategy for nuclear genes. Furthermore,
whereas mobility-shift methods are widely used for the discovery of nucleotide
substitutions, the yield of these methods has rarely been evaluated. This paper
investigates these issues in non-coding regions of ALDH2, the gene that encodes
aldehyde dehydrogenase 2 (ALDH2). Screening 20 Europeans, 20 native Americans,
and 20 Asians by using restriction enzyme and single-strand conformation
polymorphism (SSCP) analysis has revealed 16 variable sites. SSCP yields slightly
fewer than the number of nucleotide substitutions predicted by the restriction
enzyme digests. Estimates of nucleotide diversity are similar to those of other
genes, suggesting that the pattern of polymorphism in ALDH2 offers a preview of
what can be expected in many human nuclear genes. Eight of the variable sites
discovered here and four sites discovered by others have been genotyped in 756
people from 17 populations across five continents. An expectation-maximization
method has used to estimate haplotype states and frequencies. Only three
haplotypes are common worldwide, and a fourth haplotype is common in, but private
to, Asia. Although allele frequencies differ among sites, linkage disequilibrium
is almost maximal across ALDH2. This suggests that haplotype construction at
ALDH2 is particularly successful. The ALDH2 result, in conjunction with linkage
disequilibrium results from other genes, indicates that haplotype construction
will be a generally useful genomic strategy.
PMID- 10190332
TI - 1176C polymorphism in Japanese patients with glycogen storage disease type 1a.
PMID- 10190333
TI - Annotation: mood disorder in suicidal children and adolescents: recent
developments.
PMID- 10190334
TI - Practitioner review: electroconvulsive therapy in adolescents.
AB - There is increasing interest regarding electroconvulsive therapy (ECT) in young
persons but limited information about its optimal use. This paper reviews the
indications, effectiveness, and side effects of the treatment in the teenage
population and their implications for everyday clinical practice. There is
particular reference to factors influencing the clinician to recommend or advise
against convulsive therapy, steps in the assessment of patients, and consent
issues. Practical aspects of ECT administration are also examined, including
treatment locale, anaesthesia, electrode position, stimulus characteristics, EEG
monitoring, and use of psychotropics during and after the ECT course.
PMID- 10190335
TI - Infantile autism and associated autosomal chromosome abnormalities: a register
based study and a literature survey.
AB - Infantile autism is a heterogenous disorder with unknown aetiology. Evidence from
the relatively few family and twin studies suggests a genetic component. Co
occurrence or cosegregation between infantile autism and chromosomal
abnormalities may identify candidate regions, which could be tested in linkage or
association studies. The purpose of this study was to use the Danish Cytogenetic
Central Register in order to detect autosomal chromosome abnormalities associated
with infantile autism, and to review the literature for cases of autism
associated with autosomal chromosome abnormalities to identify candidate
chromosomal regions. The register-based study identified possible candidate
regions on chromosome 7q21 and 10q21.2, which have not previously been reported.
A few interesting candidate regions, 15q11-13, 16q23, and 17p11.2 were found in
the literature survey.
PMID- 10190336
TI - Childhood conduct problems, hyperactivity-impulsivity, and inattention as
predictors of adult criminal activity.
AB - This study reconsiders the relationship of childhood Attention
Deficit/Hyperactivity Disorder (ADHD) and childhood conduct problems with adult
criminal activity by clarifying the role of the cardinal behaviors associated
with the DSM-IV ADHD subtypes (inattention and hyperactivity/impulsivity). Since
their childhood (average age 9 years), 230 male and 75 female subjects have been
followed prospectively and were interviewed as young adults (average age 26 at
follow-up). Early childhood behavior ratings by parents and teachers were
examined to determine the role of conduct problems, hyperactivity-impulsivity,
and inattention in predicting adult criminal involvement as measured by both
official arrest records and self-report. Results show that both hyperactivity
impulsivity and early conduct problems independently, as well as jointly, predict
a greater likelihood of having an arrest record for males, but not for females.
For male subjects with 10 or more self-reported crimes, both early conduct
problems and hyperactivity-impulsivity were significant predictors, both alone
and in combination. Therefore, it appears that predominantly the symptoms of
hyperactivity-impulsivity, but not inattention, contribute to the risk for
criminal involvement over and above the risk associated with early conduct
problems alone.
PMID- 10190337
TI - Everyday memory deficits in children and adolescents with PTSD: performance on
the Rivermead Behavioural Memory Test.
AB - Adult post-traumatic stress disorder (PTSD) patients often report a wide range of
cognitive problems in memory, concentration, attention, planning, and judgement.
Evaluation of these cognitive aspects of PTSD in adults has helped to define the
nature of the disorder. However, there is a paucity of such work in younger
subjects. This study has employed the Rivermead Behavioural Memory Test (RBMT) to
examine cognitive factors in children and adolescents with PTSD. Eighteen child
and adolescent patients with PTSD and 22 control subjects completed the test.
PTSD subjects showed poorer overall memory performance compared with controls.
Specifically, they were worse on the prospective and orientation items of the
RBMT. The results are discussed in the light of research on everyday memory in
adults with PTSD.
PMID- 10190338
TI - Post-traumatic stress responses following liver transplantation in older
children.
AB - Eighteen children aged between 7 and 16 years who had undergone a liver
transplantation were interviewed using the Child Post-Traumatic Stress Reaction
Index (CPTS-RI) to discover if they had post-traumatic stress symptoms. A case
control design was used to define which factors were important for the
development of post-traumatic stress. Results of a one-way analysis of variance
(ANOVA), with post-traumatic stress symptom intensity as measured on the CPTS-RI
as the dependent variable, revealed a significant difference between the liver
transplantation group compared with children who had a chronic life-threatening
illness or had undergone a routine surgical operation. A post hoc (Tukey's HSD
test) statistical analysis was performed and significance at the .05 level was
found between the liver transplantation group and both the chronic illness group
and the routine surgical operation group. Our results indicate that the acute
life-threat involved in the liver transplantation contributed to the development
of post-traumatic stress. It was thought that dissociation may be important in
preventing the resolution of the trauma. Additional investigations are needed
with larger numbers in a longitudinal study beginning before the transplant to
determine the course of the PTSD symptoms and the appropriate timing of
interventions to reduce the harmful effects of these symptoms.
PMID- 10190339
TI - Quebec child mental health survey: prevalence of DSM-III-R mental health
disorders.
AB - The Quebec Child Mental Health Survey (QCMHS) was conducted in 1992 on a
representative sample of 2400 children and adolescents aged 6 to 14 years from
throughout Quebec. Prevalences of nine Axis-I DSM-III-R (American Psychiatric
Association, 1987) mental health disorders were calculated based on each
informant (for 6-11-year-olds: child, parent, and teacher; for 12-14-year-olds:
child and parent). Informant parallelism allows the classification of results of
the demographic variables associated with disorders in the logistic regression
models. This strategy applies to group variables (correlates of disorders)
whereas informant agreement applies to individual diagnoses. Informant
parallelism implies that results for two informants or more are in the same
direction and significant. In the QCMHS, informant parallelism exists for
disruptive disorders, i.e. in two ADHD regression models (child and parent)
higher rates among boys and young children, and in three oppositional/conduct
disorders regression models (child, parent, and teacher) higher rates among boys.
No informant parallelism is observed in the logistic regression models for
internalizing disorders, i.e. the patterns of association of demographic
variables with anxiety and depressive disorders vary across informants. Urban
rural residence does not emerge as a significant variable in any of the logistic
regression models. The overall 6-month prevalences reach 19.9% according to the
parent and 15.8% according to the child. The implications of the results for
policy makers and clinicians are discussed.
PMID- 10190340
TI - Post-traumatic stress reactions in children of war.
AB - The aims of this study were to estimate the rate of post-traumatic stress
reactions in Palestinian children who experienced war traumas, and to investigate
the relationship between trauma-related factors and PTSD reactions. The sample
consisted of 239 children of 6 to 11 years of age. Measures included the Rutter
A2 (parent) and B2 (teacher) scales, the Gaza Traumatic Event Checklist, and the
Child Post-Traumatic Stress Reaction Index. Of the sample, 174 children (72.8%)
reported PTSD reactions of at least mild intensity, while 98 (41%) reported
moderate/severe PTSD reactions. Caseness on the Rutter A2 scale was detected in
64 children (26.8%), which correlated well with detection of PTSD reactions, but
not with teacher-detected caseness. The total number of experienced traumas was
the best predictor of presence and severity of PTSD. Intervention programmes for
post-war children need to be evaluated, taking into account developmental and
cultural aspects, as well as characteristics of the communities involved.
PMID- 10190341
TI - The use of orthographic analogies in learning to read Chinese.
AB - Two studies, comprising training in phonological analogy and semantic analogy
with pre-and post-training assessments, were conducted to investigate whether
young children made orthographic analogies in learning to read a nonalphabetic
script, Chinese, as alphabetic readers do. Twenty Chinese first-graders and 20
third-graders participated in each of the studies. The results showed that not
only the third-graders, but also the first-graders made phonological analogies by
the phonetic (i.e. the orthographic component in a Chinese character that
provides sound cues) and semantic analogies by the radical (i.e. the orthographic
component that provides meaning cues). It was, therefore, suggested that the
roles and functions of the phonetics and radicals could be taught explicitly in
school from an early age to help improve children's reading skills.
PMID- 10190342
TI - Effects on later adjustment of living in a stepfamily during childhood and
adolescence.
AB - This paper examines the effects of living in a stepfamily during childhood and
adolescence on a range of psychosocial outcomes at age 18 years. Data collected
during an 18-year longitudinal study were used to examine a sample of 907
children with respect to: exposure to living in a stepfamily during the period
from age 6 to 16 years; measures of psychosocial outcomes including mental
health, antisocial behaviour, substance use, restricted life opportunities, and
sexual risk-taking at age 18 years; and measures of prospectively collected
confounding factors. The analyses revealed that children exposed to living in a
stepfamily for the first time between ages 6-16 years had elevated risks of a
range of psychosocial outcomes at 18 years. These included elevated risks of: (1)
juvenile offending; (2) nicotine dependence; (3) abuse or dependence on illicit
substances; (4) leaving school without qualifications; (5) early onset of sexual
activity; and (6) multiple sexual partners. However, these risks were reduced
substantially when psychosocial outcomes were adjusted for the confounding
effects of antecedent factors such as: family socioeconomic characteristics:
family history of instability, adversity, and conflict; mother's age,
religiosity, and smoking; child gender; and preexisting child conduct and
attentional problems. After adjustment, the odds ratios between exposure to a
stepfamily and adolescent outcomes were nonsignificant. Additional analysis
revealed that there were no significant differences in outcomes for boys and
girls exposed to stepfamilies. It was concluded that although young people
exposed to living in a stepfamily had increased risks of poor psychosocial
outcomes, much of this association appeared to be spurious, and arose from
confounding social, contextual, and individual factors that were present prior to
the formation of the stepfamily.
PMID- 10190343
TI - Differences between school classes in preschoolers' psychosocial adjustment:
evidence for the importance of children's interpersonal relations.
AB - We examined differences between school classes with respect to three aspects of
psychosocial adjustment at school, namely the extent that children in the class
liked to play with each other, the number of teacher-reported behaviour problems,
and children's feelings of wellbeing at school. The sample consisted of 1282 4-
to 5-year-olds from 94 school classes and 51 schools, but due to nonresponse
actual sample sizes were somewhat smaller for most analyses. Multilevel analyses
showed that on average 87% of the variance was at the child level, 11% at the
class level, and 3% at the school level. This indicated that a non-negligible
amount of variance could not be accounted for by factors at the child level.
Furthermore, this variance was mainly associated with differences between classes
instead of differences between schools. A set of variables that pertained to
sociodemographic characteristics of schools, school facilities, organisational
aspects of classrooms, and the teacher did not provide an adequate explanation
for the differences in adjustment levels. In contrast to these traditional
variables, social network indices yielded substantial correlations, showed
consistent trends across the different adjustment measures, and fulfilled the
necessary requirement that to explain differences between school classes the
predictor variables themselves should differ for classes within the same school.
These results suggested that aspects of the interpersonal relations of children
in the classroom such as proximity, integration, and the amount of contact could
be determinants of differences between school classes in psychosocial adjustment.
PMID- 10190344
TI - The EAS temperament questionnaire--factor structure, age trends, reliability, and
stability in a Norwegian sample.
AB - A population-based sample of Norwegian children aged 18 months (N = 921), 30
months (N = 784), and 50 months (N = 737) was examined with the EAS Temperament
Survey (Buss & Plomin, 1984). The factor structure, psychometric properties, and
stability estimates of the instrument were assessed. A cross-validation of the
temperament factors of Emotionality, Activity, and Shyness show that the
covariance structure conforms with the three scales described by Rowe and Plomin
(1977) and Boer and Westenberg (1994). When items from the experimental scale of
Sociability were included in the analysis, a four-factor solution confirmed the
separate usability of this scale as well. The factor structure does not seem to
vary substantially with the age of the children. The scores on the four
temperament scales show high stability from one time of measurement to the next.
Although no strong gender differences were found, there were significant age
trends. Emotionality and Shyness increased from 18 to 50 months, while Activity
and Sociability decreased. The study confirmed the structure and stability of the
EAS over 3 years among young children, providing support for its use with
children as young as 18 months.
PMID- 10190345
TI - The self-systems of aggressive children: a cluster-analytic investigation.
AB - The purpose of the present study was to identify clinically relevant subtypes of
aggressive children based on measures of children's self-systems and significant
others' perceptions of relationship quality. In a sample of aggressive second-
and third-graders, a cluster analysis of these children's perceptions of support
and significant others' (mother, teacher, and peers) perceptions of relationship
quality revealed one subgroup in which self- and other-ratings were both below
the group mean (concordant-negative), one in which both were above the sample
mean (concordant-positive), and one in which they were discrepant (high child
report and low other-report). All three clusters were rated as more aggressive
than controls. However, children in the discrepant group were rated as
considerably more aggressive and delinquent than those in the two concordant
clusters, who did not differ from each other on measures of internalizing and
externalizing behaviors. Results are discussed from an attachment perspective and
in terms of the clinical significance of this self-other discrepancy.
PMID- 10190346
TI - Individual differences in young children's IQ: a social-developmental
perspective.
AB - From a sample of middle-class mothers and their 3-year-old children, a selected
group of 36 mothers were divided into 2 groups according to the quality of their
responses to the Adult Attachment Interview as a Questionnaire (Crandell,
Fitzgerald, & Whipple, 1997). Twenty mothers provided coherent accounts of their
early parent-child relationships (secure) and 16 mothers provided idealised,
entangled, or otherwise incoherent accounts of their early parent-child
relationships (insecure). The mothers were administered an abbreviated version of
the WAIS-R and the children were given an abbreviated version of the Stanford
Binet Intelligence Scale. The quality of mother-child interactions was assessed
by videotaping a 20-minute play episode and clean-up period, and by rating the
degree of synchrony according to a modified version of the Belsky Parent-Child
Interaction System (Whipple, Denburg, & Davies, 1993). The results were that
children of secure mothers scored 19 points higher on the Stanford-Binet test
compared to children of insecure mothers. (The adjusted mean difference was 12
points when maternal IQ, education, and family SES were taken into account.) The
group difference in the children's IQ remained significant when comparisons were
made between a subgroup of 12 secure and 12 insecure mothers who were matched for
maternal IQ. Finally we examined the subgroup of 16 cases where child IQ scores
were either 10 points higher or lower than maternal IQ. In all 6 cases where
child IQ was at least 10 points below maternal IQ, the child had a mother who was
insecure; in contrast, only 4 of the 10 children who had IQ scores 10 points
higher than maternal IQ had an insecure mother. In terms of parent-child
interaction patterns, there was suggestive evidence that the degree of parent
child synchrony was also related to child IQ. The results suggest important
social-developmental contributions to young children's performance on
standardised tests of intellectual ability.
PMID- 10190347
TI - Avoidant/ambivalent attachment style as a mediator between abusive childhood
experiences and adult relationship difficulties.
AB - The role of attachment style, self-esteem, and relationship attributions as
possible mediators between abusive childhood experiences and difficulties in
establishing supportive love relationships in adulthood were investigated in a
sample of women known to be at risk of experiencing relationship problems.
Measures of child abuse, the quality of love relationships, and the three
potential mediators were made concurrently in adulthood. Participants who had
experienced child abuse were found to be six times more likely to be experiencing
difficulties in the domain of adult love relationships than those who had not.
Self-esteem and relationship attributions were not found to be related to child
abuse. When both child abuse and avoidant/ambivalent attachment style were
considered together avoidant/ambivalent attachment style, but not child abuse,
was found to be related to relationship difficulties. These findings indicate
that avoidant/ambivalent attachment style, but not self-esteem and relationship
attributions, is a mediating factor in the route from child abuse to adult
relationship abilities.
PMID- 10190348
TI - Maternal age and educational and psychosocial outcomes in early adulthood.
AB - The relationships between maternal age (at birth) and educational and
psychosocial outcomes at age 18 were examined in a birth cohort of 1025 New
Zealand children. This analysis indicated the presence of consistent tendencies
for increasing maternal age to be associated with declining risks of educational
underachievement, juvenile crime, substance misuse, and mental health problems.
Children with teenage mothers had risks of later adverse outcomes that were 1.5
to 8.9 times higher than the risks for offspring of mothers aged over 30.
Subsequent analyses revealed that the associations between maternal age and later
educational and psychosocial outcomes were largely, but not wholly, explained by
associations between maternal age and the child-rearing practices and home
environments experienced by children. In general, increasing maternal age tended
to be associated with more nurturant, supportive, and stable home environments.
In turn, these linkages between maternal and childhood environment explained most
of the association between maternal age and later outcomes. The theoretical and
applied implications of these results are considered.
PMID- 10190349
TI - Right-sided colonic diverticular disease as a source of lower gastrointestinal
bleeding.
AB - Right-sided colonic diverticular disease is a distinct disease entity uncommon in
the West. Occasionally, the condition may be complicated by hemorrhage and
present as lower gastrointestinal bleeding. We report a series of 25 cases of
bleeding right colon diverticulosis and discuss its presentation and management.
Patients were selected from the colonoscopic reports of all 190 patients
presented with suspected acute lower gastrointestinal bleeding in National
University Hospital, Singapore, from 1988 to 1994. Fifty-seven patients (30%) had
bleeding diverticulosis in which 25 patients (44%) suffered from right-sided
disease. Sixty-four per cent of patients had a history of hypertension. Patients
presented with either fresh blood in stools or melena. Fifteen patients (60%)
required blood transfusion (median, 2 units). Colonoscopy showed blood clots in
the right colon in 15 cases (60%) and active bleeding from the right colon
diverticula in 3 patients (12%). The bleeding stopped spontaneously in 16
patients (64%). The other 9 patients required surgery because of continuous or
recurrent bleeding. All had a right hemicolectomy performed. The hospital stay
was 13 days in this group, compared with 5 days for those undergoing conservative
treatment (P = 0.0004). There were no deaths. No patients had further bleeding
episodes during a median 7-month follow-up.
PMID- 10190350
TI - What is the paradigm: hospital or home health care for pressure ulcers?
AB - A home health care (HHC) referral should link the patient in a cost-effective
fashion to the physician, home care, and instructions regarding ulcer management.
Twenty-one patients (mean age, 74.6 years) had stage III pressure ulcers (<100
cm2) and an involved family member at home. Risk and contributing factors
included cardiac disease (n = 9), hypertension (n = 14), end-stage renal disease
(n = 7), smoking (n = 11), diabetes (n = 8), chronic brain syndrome (n = 14),
cerebrovascular accident (n = 5), and above-the-knee amputation (n = 2).
Treatment regimens included standard wound care, pressure relief and, where
appropriate, culture-specific antibiotics, as well as a rehabilitation program.
Home care progressively decreased the frequency of the nurse HHC and physician
office visits. Resolution of the pressure ulcer varied from 6 to 32 weeks. Only
two patients had progression of their wound and required hospital readmission.
The billable fees included: 1) an office visit, $30.00 (medicare reimbursement,
$14.00); 2) the HHC nurse visit, $159.00 (medicare reimbursement, $105.00); 3)
supplies, $75.00 to $150.00/week (variable reimbursement); 4) hospitalization,
$400.00 to $900.00/day; and 5) a chronic-care bed, $400.00 to $750.00/day. HHC,
given a responsible support team and an involved family member, was more socially
and financially acceptable than an inpatient facility. Intermittent physician
visits with HHC proved safe and reliable, with 90 per cent successfully healing
their wounds.
PMID- 10190351
TI - Factors affecting the surgical management of infective endocarditis.
AB - Congestive heart failure and septic embolism complicate the clinical course of
patients with infective endocarditis (IE). This study reviews the clinical
records of patients with systemic disease secondary to IE and stratifies their
disease severity according to individual risk factors and medical, and surgical
interventions. The hospital records of all patients presenting to our institution
from 1992 through 1997 with heart valve destruction secondary to IE were
reviewed. Ten patients with hemodynamically significant valve lesions were
included in this study: seven with aortic valve disease and two with mitral valve
disease, and one with combined aortic and mitral valve lesions. All were
diagnosed by echocardiogram. All ten patients experienced systemic septic
arterial emboli: four intracranial lesions, four visceral lesions, and three
extremity arterial occlusive events. Two patients required peripheral arterial
repair. Cultures revealed infection secondary to Staphylococcus aureus in five,
Streptococcus species in three, Coxiella species in one, and an unidentified
organism in one patient. Seven patients underwent valve replacement. Three
patients died from their disease processes. Statistical significance was
established by Wilcoxon rank analysis with a two-tailed P < 0.05. Patients with
IE secondary to staphylococcal infections suffered a more acute and virulent
disease process (P = 0.04), with a 40 per cent mortality rate in the first 48
hours. There was no increased incidence of embolization associated with longer
duration of symptoms (P = 0.32). Surgical repair conferred improved clinical
outcome as compared with no surgical intervention (P = 0.03). Improved patient
outcome was associated with nonstaphylococcal infection (P = 0.02), and a
successful initial antibiotic regimen (P = 0.03). Peripheral arterial repair was
successful in both cases.
PMID- 10190352
TI - Comparison of arcuate-legged clipped versus sutured hepatic artery, portal vein,
and bile duct anastomoses.
AB - Attempts at improving anastomoses have included the development of stapling
techniques. Our purpose was to evaluate arcuate-legged clipped versus standard
sutured anastomoses of the hepatic artery (HA), portal vein (PV), and bile duct
in a porcine liver transplantation model. Two groups of pigs were studied
intraoperatively and 1 day after liver transplantation. A control group underwent
sutured anastomosis of PV and HA with polypropylene and of bile duct with
polydioxanone (n = 8). An experimental group underwent anastomoses with arcuate
legged clips (n = 8). We analyzed the time to perform anastomosis and flows
before and at various time points after anastomosis. In addition, patency and
histology of the anastomoses were evaluated 1 day after operation, including a
fibrin-thrombosis score, medial injury, and inflammation score. Times to complete
HA and PV anastomoses were not different between clipped and sutured groups.
However, the time was shorter to complete bile duct anastomosis with clips than
with sutures (6.3 +/- 1.1 minutes and 13.3 +/- 2.0 minutes, respectively). Flows
through HA anastomoses were not different between groups, but flow through the PV
was higher in clipped compared with sutured anastomosis (P = 0.06). Patency was
100 per cent with no leaks for all three anastomoses in both groups. Histologic
data were similar between vascular anastomotic groups. Sutured bile duct
anastomoses revealed mild smooth muscle injury in 75 per cent whereas clipped
bile duct anastomoses displayed no smooth muscle injury. We conclude that arcuate
legged clipped anastomosis represents a viable option to sutured anastomoses of
the PV, HA, and bile duct anastomoses. Bile duct anastomoses were completed in
less than half the time and with less tissue damage documented histologically.
PMID- 10190353
TI - Atlanto-occipital subluxation/dislocation: a "survivable" injury in children.
AB - Atlanto-occipital dislocation occurs more often in children due to the laxity of
the ligamentous structures anchoring the occiput to the axial skeleton. The
mechanism of action usually involves a sudden acceleration-deceleration force on
the head of the child. The dislocation usually severs the spinal cord at the
foramen magnum, resulting in acute respiratory arrest. We have managed four
patients who sustained this injury and arrived at our trauma center with signs of
life. Two patients were hemodynamically unstable, had positive diagnostic
peritoneal lavage, and underwent splenectomy. Both patients had obvious
separation of the occiput and C1 on lateral cervical spine films. Both remained
very unstable and died soon after celiotomy. The other two patients were
stabilized, and both met criteria for brain death; one family agreed to organ
donation. A 5-year analysis revealed 57 pediatric deaths, with 10 patients
sustaining atlanto-occipital dislocations (17.5%). Nine of 10 patients sustained
other injuries, but in only 2 patients were the injuries immediately life
threatening. With continued improvement in emergency medical systems and
pediatric trauma care, we can expect to see more pediatric patients with this
injury arriving in trauma centers with signs of life. In our experience, 50 per
cent of patients may meet organ donor criteria, and our incidence of this injury
(17.5%) reveals atlanto-occipital dislocation as a major contributor to pediatric
trauma mortality.
PMID- 10190354
TI - Severe anal ulceration secondary to Histoplasma capsulatum in a patient with HIV
disease.
AB - Severe fungal infections have become increasingly common in the immunocompromised
patient, including those infected with human immunodeficiency virus. Histoplasma
capsulatum occurs in about five per cent of acquired immunodeficiency syndrome
patients in the endemic areas of the Mississippi and Ohio River Valley.
Immunocompromised patients who present with severe ulceration and suppuration of
the anus require exam under anesthesia and thorough laboratory evaluation for
opportunistic infections. Thus, surgeons play a critical role in diagnosis and
initiation of treatment. A case of infiltrating H. capsulatum of the anus is
presented, including the natural history, presentation, diagnosis, and treatment.
PMID- 10190355
TI - Nonendarterectomy procedures of the carotid artery: a five-year review.
AB - Although the efficacy of carotid endarterectomy has been well established,
nonendarterectomy procedures of the carotid bifurcation have only sporadically
been reported. Of 334 consecutive nontraumatic carotid procedures performed on
321 patients from July 1992 until May 1997, 306 (91.6%) were carotid
endarterectomies, 14 (4.2%) were carotid-subclavian bypasses/transpositions, and
14 (4.2%) were nonendarterectomy procedures of the carotid artery. These latter
14 cases (nine females and five males; mean age, 63 years) were all symptomatic
(neurological or painful mass) and included carotid kink/coil resection (n = 3;
0.9%), endarterectomy and vertebral transposition (n = 2; 0.6%), carotid aneurysm
resection (n = 2; 0.6%), carotid body tumor resection (n = 2; 0.6%), carotid
stump ligation/external endarterectomy (n = 1; 0.3%), infected/bleeding carotid
patch removal with vein graft replacement (n = 1; 0.3%), saphenous vein graft
replacement (n = 1; 0.3%), carotid dilatation for fibromuscular dysplasia (n = 1;
0.3%), and descending aorta to carotid bypass (n = 1; 0.3%). With 30 day follow
up complete for all 334 carotid operations, 10 perioperative strokes (2.9%) and
five deaths (1.5%) occurred for a combined stroke/death rate of 3.3 per cent. Of
the 14 nonendarterectomy carotid artery operations, there were no strokes or
deaths; with mean follow-up of 13 months, 13 patients (92.9%) are asymptomatic,
patent, and disease-free. Three severe transient cranial nerve (CN) neuropraxias
(21.4%), one myocardial infarction (7.1%), and one late death (mesenteric
ischemia at 2 months), however, occurred. Although no statistical differences in
stroke, death, and stroke/death occurred between the endarterectomy versus the
nonendarterectomy group, transient CN injury was more common in the
nonendarterectomy group (21.4% versus 4.1%; P = 0.027). Although
nonendarterectomy procedures of the carotid bifurcation are infrequently needed,
they seem safe, effective, and indicated in selected patients, despite a higher
incidence of transient CN injury.
PMID- 10190356
TI - The surgical intensive care unit as a cost-efficient substitute for an operating
room at a Level I trauma center.
AB - Critically ill patients in the surgical intensive care unit (SICU) continue to
require operative procedures. Traditionally, this has meant the transport of
these critically ill patients out of the safe, monitored confines of the SICU to
the operating room (OR). This can be hazardous to the patient, as well as
expensive. Performing the procedures in the OR can avoid both the dangers of
transport and the expense of the OR. Herein is a descriptive study of 80
procedures performed on 36 patients in the SICU. We believe that these data show
that the SICU can be a cost-effective alternative to the OR in a trauma center in
critically ill patients. Significant cost savings may be realized without
increasing the iatrogenic or infectious complications.
PMID- 10190357
TI - Management of vascular prosthetic infections: results of long-term follow-up.
AB - An infected vascular prosthesis is a risk to life and limb, with many of the
infections insidious in nature. A retrospective analysis with a minimum 49-month
follow-up identified 18 patients (mean age, 61.3 years) with culture-positive
infections and exposed prosthetic grafts in the infrainguinal region. All
patients were managed with muscle flaps. Mean follow-up was 59 months, with a
long-term salvage of infected prosthetic grafts in 16 of 18 patients; there was
no loss of life or limb. Early, aggressive reconstruction of infected prosthetic
grafts using a muscle flap technique saves graft, leg, and patient.
PMID- 10190358
TI - Acute thermal injury to the canine jejunal free flap: electrocautery versus
ultrasonic dissection.
AB - Electrocautery-induced thermal injury contributes to morbidity and mortality
after laparoscopic surgery. Ultrasonic dissection is an alternative technique
that may produce less thermal injury. We compared the amount of acute thermal
injury caused to jejunal free flaps isolated with laparoscopic electrosurgical
instruments with that caused by ultrasonic dissection (laparoscopic coagulating
shears). Canine jejunal free flaps were isolated by electrocautery or laparosonic
coagulating shears and remained viable on a vascular pedicle. After a period of
ischemia and reperfusion, the flaps were resected to simulate harvesting and
reimplantation. Thermal injury was observed at the site of dissection and was
graded histologically. At the margin of the jejunal free flaps, the laparosonic
coagulating shears produced less thermal injury (score, 2.2 at level 3) than the
electrocautery grasping forceps (score, 3.7 at 35 W and 4.1 at 70 W). The
laparosconic coagulating shears produced less thermal injury to a jejunal free
flap than did electrocautery. Ultrasonic dissection is an alternative to the
complications produced by electrocautery during laparoscopic dissection.
PMID- 10190359
TI - Limited utility of preoperative studies in preparation for colostomy closure.
AB - Numerous diagnostic and therapeutic practices are used in an attempt to reduce
the morbidity of colostomy closures. Our principal aim was to evaluate the role
of preoperative studies, specifically barium enemas and endoscopic examinations,
performed before colostomy closures. Additionally, we wished to identify other
practices involved in the perioperative management of patients undergoing
colostomy closure that influenced morbidity. The records of 100 consecutive
patients who underwent elective colostomy closure at University of Louisville
Hospital between January 1989 and July 1995 were reviewed. Wound infection was
the most common complication (12%). Various bowel preparations were equivalent in
efficacy and did not influence the complication rate. Intermittent wound
irrigation with antibiotics for 3 days postoperatively, via subcutaneous drains,
was associated with a low incidence of incision infection. Preoperative barium
enema or sigmoidoscopy were often performed but rarely useful. Performing these
examinations merely increased hospital cost without a corresponding decline in
morbidity.
PMID- 10190360
TI - Pulmonary embolus after vena cava filter placement.
AB - This report characterizes risk factors in patients who suffer pulmonary embolus
(PE) after insertion of vena caval filter (VCF) and formulates an organized
diagnostic and therapeutic plan of management. Three hundred eighteen patients
were included in a review of patients undergoing insertion of VCF from 1989 to
1995. Ten patients (six men and four women, ages 25-72 years) from this group
(3.1%) experienced PE after VCF insertion. Risk factors for deep venous
thrombosis were documented in these ten patients. Venacavography was performed
after diagnosis of PE. Thrombus length measured from the apex of the filter was
used to determine further therapy. Thrombus 5 cm or greater in length was treated
with a second VCF (VCF-2). Smaller clots were treated with anticoagulation (AC).
All patients treated with AC underwent repeat vena caval study (CT scan or
venacavagram) 10 days to 18 months after treatment. PE occurred from 8 days to
5.5 years after original VCF insertion. Five patients suffered PE longer than 6
months (range, 21-66 months; mean, 39 months) after VCF insertion. Venacavagrams
demonstrated thrombus in all ten patients with PE. Six patients were treated with
VCF-2 and four patients with AC. Dissolution of thrombus was seen on follow-up in
all patients given AC. All 10 patients harbored at least two risk factors for
deep venous thrombosis. Malignancy was found in only two patients. Five patients
were found to have procoagulant states characterized by decreased levels of anti
thrombin III or protein C or S. No postoperative deaths or early recurrent PE
occurred. One patient experienced another PE 5 years after treatment with AC when
she discontinued warfarin. Contraindications to AC appeared to be self-limited,
and all patients were discharged on warfarin. No significant bleeding occurred
during early follow-up. Our findings confirm the reliability and low complication
rate for VCF. Patients experiencing PE after insertion of VCF mandate an
aggressive diagnostic approach that should include venacavography and a search
for identifiable risk factors including procoagulant state. Treatment with AC and
insertion of a second VCF both give favorable results. All patients appear to
benefit from short- or long-term warfarin therapy, and contraindications to AC
frequently are self-limited. Therapy based on clot size warrants further study.
PMID- 10190361
TI - Abdominal surgery in chronic hemodialysis patients.
AB - The number of patients with end-stage renal disease who benefit from chronic
dialysis is steadily increasing. This study was designed to assess abdominal
surgery in chronic hemodialysis (CHD) patients. A 7-year retrospective study was
conducted including all the patients on CHD who underwent abdominal surgery in
our unit. These patients were separated into an elective and an emergency surgery
group. Forty-three patients underwent surgery. In the elective surgery group (18
patients), the most common diseases were colorectal cancer, symptomatic
gallbladder stones, and hernia. There was no death related to surgery in this
group, and only one patient developed a complication (5%). In the emergency
surgery group (25 patients), the most common diseases were mesenteric ischemia
and gastrointestinal bleeding from angiodysplasia. Complications occurred in 10
patients (total morbidity rate, 40%), and 6 of them died (mortality rate, 24%).
Gastrointestinal elective surgery in patients on CHD can be performed with low
morbidity and mortality rates. The emergency group was differentiated by the high
prevalence of bleeding from angiodysplasia and mesenteric infarction, as well as
its high surgical mortality rate.
PMID- 10190362
TI - Palliative surgery for far-advanced gastric cancer: a retrospective study on 305
consecutive patients.
AB - Few reports of the Western countries have investigated the value of palliative
surgery for stomach cancer. The aim of this study was to evaluate the results of
palliative surgery in a large series of patients affected by gastric carcinoma,
consecutively treated by the same surgical team. The hospital records of 305
patients affected by gastric cancer who did not undergo surgical treatment or who
underwent a palliative surgical procedure at our unit between 1981 and 1995 were
reviewed. Univariate and multivariate analyses were used to calculate the 5-year
survival probabilities with respect to the following variables: demographic data,
tumor location and gross appearance, spread of the disease, histological type
according to P. Lauren, and type of treatment. Multivariate logistic regression
analysis showed that resectional surgery and tumor spread limited to local sites
were independently associated with better survival. The study indicates that even
though there are host-related factors that govern survival in far-advanced
stomach cancer, the type of surgery can have a significant effect on prognosis;
resectional surgery should be undertaken whenever possible in such patients.
PMID- 10190363
TI - Hypothermia does not result in more complications after colon surgery.
AB - Our objective was to determine the incidence of complications in postoperative
patients who were either normothermic or hypothermic. A recent, widely publicized
paper concluded that the maintenance of normothermia could reduce the incidence
of infectious complications and shorten hospitalization in patients undergoing
colorectal surgery. However, some controversy arose regarding the methods of this
paper. Patients were deliberately rendered hypothermic, were given more than 3.5
days of prophylactic antibiotics and were transfused significantly more units of
blood. We reviewed the charts of 150 consecutive patients who underwent elective
partial or subtotal colectomy with primary anastomosis. Among the key items
analyzed were intraoperative and postoperative temperature, use of warming
devices, duration of surgery, transfusions, interval to oral intake and bowel
function, length of stay, complications, infections, and laboratory values.
Hypothermia was defined as intraoperative temperature <95.5 degrees F. There were
101 normothermic patients and 49 hypothermic patients. Hypothermic patients had a
mean age of 68.7 years versus 66.8 for the normothermic patients (P = 0.472).
Comorbidities were similar in both groups. Warming devices were used in >90 per
cent of the patients in both groups. The rates of postoperative infections and
complications were similar in both groups. Postoperative lengths of stay were
also not different. Despite finding that one-third of our patients were
hypothermic during elective colon resection, hypothermia had no effect on outcome
variables. In contrast to the previous study, the incidence of infectious
complications was identical in our patients. Before ascribing postoperative
complications and increased resource utilization as adverse effects of
hypothermia, further studies are indicated.
PMID- 10190364
TI - Gunshot wounds below the popliteal fossa: a contemporary review.
AB - The management of extremity injuries above the knee has been well described, but
the evaluation and treatment guidelines for penetrating injuries below the
popliteal crease has received less attention. A 6-year retrospective review of
100 patients who sustained isolated below-knee gunshot wounds. Patients with
proximal extremity, torso, or head wounds were excluded from review so that we
could focus on principles of managing below-knee wounds. All patients were
evaluated with complete physical examination, ankle-brachial index, and plain X
rays. One patient presented with hemodynamic instability. Twenty-four patients
underwent arteriography based on physical examination, an ankle-brachial index
less than 0.9, or both. Twenty-two vascular injuries were identified in 19
patients, and an additional injury was found in a patient who went directly to
surgery for pulsatile bleeding. Six of these 22 vascular injuries required
treatment for bleeding or arteriovenous fistula. Treatment was by embolization in
5 and surgical ligation in 1. Thirteen patients had compartment syndromes. Thirty
five patients had fractures, and ten (29%) of these had an associated vascular
injury. Four patients had peroneal nerve injuries, and three of these had long
term disability. No limb loss or death occurred. We conclude that patients with
low-velocity below-knee gunshot wounds sustain fractures, vascular injuries,
compartment syndromes, and nerve injuries, in decreasing order of frequency.
Arteriography and embolization may be useful to control bleeding; vascular
reconstruction was unnecessary in our experience, and limb loss did not occur.
PMID- 10190365
TI - Acute acalculous cholecystitis in young patients without predisposing factors.
AB - We report the atypical presentation of acute acalculous cholecystitis in four
young, otherwise healthy patients. These cases emphasize the fact that the
traditional concept of this disease as being associated with trauma, major
surgery, or other pathology may no longer be true, and an important number of
cases may appear de novo in patients without any predisposing factors.
PMID- 10190366
TI - The use of delayed computerized tomography in the evaluation of blunt abdominal
trauma: a preliminary report.
AB - This purpose of this study was to analyze the use of abdominal computed
tomography (CT) imaging in patients with possible blunt abdominal trauma. A
retrospective analysis of all trauma patients over a 1-year period (1993-1994)
was conducted, with prospective study protocol in 52 patients using serial
abdominal exam and hematocrits (Hcts) instead of abdominal CT for evaluation of
blunt abdominal trauma. Urgent abdominal CT was used as the initial diagnostic
test for evaluation of blunt abdominal trauma in 813 patients over this 1-year
period. CT was obtained in 379 (46.6%) of these patients who arrived
hemodynamically stable (admission systolic blood pressure > or = 90), had a
Glasgow Coma Scale > 13, and had admission Hct > or = 35 because of distracting
injuries, possible traumatic brain injury, or alcohol/drug use, which might
render the abdominal physical exam unreliable. Only 47 CT scans (12.4%) were
positive, and three patients (0.8%) required laparotomy. In an effort to more
efficiently use abdominal CT, we performed a prospective study in 52 patients
with possible blunt abdominal trauma, admission systolic blood pressure > or =
90, Hct > or = 35, Glasgow Coma Scale > 13, and a normal abdominal exam on
admission. These patients were followed with serial abdominal examinations and
Hcts every 6 hours for 24 hours, and delayed CT, when applicable. CT was obtained
in seven patients (13.5%) for evaluation of fall in Hct or abnormal abdominal
examination; all were negative for abdominal injury. A protocol using serial
abdominal exams, Hcts, and delayed abdominal CT imaging may be useful in select
patients to decrease the high number of negative routine abdominal CTs that are
obtained in the evaluation of blunt abdominal trauma.
PMID- 10190367
TI - Does the length of the interposed segment in the Henley procedure influence
duodenogastric reflux? An experimental study.
AB - This study assesses duodenogastric reflux (DGR) using 99mTechnetium-diisopropyl
iminodiacetic acid in unoperated dogs and in dogs 28 days after a Billroth II
gastrectomy and 28 days after the Henley procedure. Fourteen mongrel dogs were
divided randomly into two groups of seven each, according to the length of the
interposed jejunal segment used (Group A 10 cm; Group B, 20 cm). All dogs were
subjected to a Billroth II gastrectomy, followed by the Henley procedure 30 days
later. In Group A, DGR was significantly lower in the preoperative period
(median, 0.0%; range, 0.0-0.02%) than after gastrectomy (median, 0.13%; range,
0.08-0.70%) and the Henley procedure (median, 0.12%; range, 0.06-0.22%), but did
not differ significantly after gastrectomy and jejunal interposition. In Group B,
DGR was significantly higher after gastrectomy (median, 0.15%; range, 0.10-0.64%)
than in the preoperative period (median, 0.00%; range, 0.00-0.09%) or than after
the Henley procedure (median, 0.00%; range, 0.00-0.7%). DGR did not differ
significantly between the preoperative period and after Henley procedure. After
jejunal interposition, DGR was significantly higher in Group A than in Group B.
The Henley procedure is effective in preventing DGR when the interposed segment
is 20 cm in length.
PMID- 10190368
TI - A clinical comparison of Dacron patch closure of small-caliber carotids compared
with primary closure of large-caliber carotids after endarterectomy.
AB - The objective was to study results of carotid endarterectomies performed between
1975 and 1991, comparing primary closure to Dacron patch closure. This was a
retrospective study. Data from patient follow-up by physical examination, chart
review, and Duplex study were used. Scan data were obtained in 92 of the primary
cases, at a mean of 5 years postoperatively, and in 63 of the patch cases, at a
mean of 4.1 years postoperatively. During this period, 269 endarterectomies were
closed primarily and 101 were closed with a knitted Dacron patch. Twenty patients
in the primary group and nine patients with patch closure were lost to follow-up,
which extended for up to 12.5 years, with a mean of 4.7 +/- 3.6 years. No acute
closures, infections or aneurysms developed in either group. Perioperative stroke
incidence was 4.1 per cent for primary closure and 3.0 per cent for the patch
group (P > 0.05). Late stenosis occurred in 17.3 per cent of the primary group
and 11.1 per cent of the patch closure group (P > 0.05). Five-year survival was
76.2 per cent in the primary group, compared with 79.2 per cent for patch
closure. Late stroke incidence was 2.8 per cent in the primary group and 3.3 per
cent in the patch closure group. Results of smaller (< or = 3.5 mm) carotid
arteries closed with knitted Dacron patches are equivalent to those of larger
carotid arteries closed primarily.
PMID- 10190369
TI - Prevention of adhesions to polypropylene mesh in a rabbit model.
AB - The purpose of this study was to develop a quantitative model for evaluating
adhesion formation and to determine whether Seprafilm (HAL-F) bioresorbable
membrane (Genzyme Corp., Cambridge, MA) is effective in preventing adhesions to
polypropylene mesh (PPM). PPM has been shown to be an effective material for the
repair of abdominal wall defects. One disadvantage of PPM is its tendency to form
dense adhesions when in contact with abdominal viscera. HAL-F, a sodium
hyaluronate/carboxymethylcellulose absorbable membrane, has been shown to prevent
adhesion formation after midline closures. Its efficacy in preventing adhesions
to PPM has not been examined previously. A 5 x 7-cm anterior abdominal wall
defect was created in 24 New Zealand White rabbits. This defect was then repaired
with PPM. In the experimental group, a 5 x 7-cm piece of HAL-F was placed between
the mesh and the abdominal viscera. At 30 days, the animals were killed and
adhesions were categorized and quantified using digital image analysis of inked
specimens. The strength of mesh incorporation into surrounding tissues was also
examined using an Instron tensiometer. The formation of adhesions between the
viscera and mesh repair was significantly reduced by the use of HAL-F. The
surface area involved for bowel adhesions was reduced 94 per cent (P = 0.00132).
The strength of incorporation was not adversely affected. HAL-F is highly
effective in preventing adhesions to PPM, without adversely effecting the
strength of mesh incorporation.
PMID- 10190370
TI - To cut or not to cut: the evolution of exploratory laparotomy for abdominal
gunshot wounds.
PMID- 10190371
TI - Re: The etiology of intestinal obstruction in patients without prior laparotomy
or hernia.
PMID- 10190372
TI - Clinical pathways for general surgeons: acute lower GI bleeding--diverticulosis.
PMID- 10190373
TI - Financing medical student education in departments of internal medicine.
PMID- 10190374
TI - The association between low bone mass at the menopause and cardiovascular
mortality.
AB - BACKGROUND: Low bone mineral density in late postmenopausal women has been
associated with increased nontrauma mortality. We investigated whether bone mass
in women soon after menopause was also associated with the risk of mortality in
later life. METHODS: Between 1977 and 1988, two samples of healthy women were
enrolled; one group soon after the menopause (age 50 +/- 2 years [mean +/- SD], n
= 309) and another later after menopause (age 70 +/- 2 years, n = 754). The
baseline visit included a medical examination and a measurement of bone mineral
content in the distal forearm. In 1994, vital status was checked. All causes of
death were registered, excluding those that were due to trauma or suicide.
Multivariate relative risks (RR) and 95% confidence intervals (CI) were
determined. RESULTS: In the early postmenopausal group, each decrease of one SD
(0.4 g/cm) in bone mineral content was associated with a 43% increase in
mortality (RR = 1.4; 95% CI 1.0 to 2.0; P < 0.05). When only cardiovascular death
was considered, the relative risk of dying within 17 years of the menopause was
increased 2.3-fold (95% CI 1.0 to 5.3; P < 0.05). Correspondingly, a 70-year-old
woman with a bone mineral content 1 SD below the mean for her age had a 1.8-fold
increased risk of dying from cardiovascular disease (95% CI 1.0 to 3.2; P =
0.06). Expressed as quartiles, women with bone mass in the lowest quartile had
twice the risk of cardiovascular death compared with those in the highest
quartile. A prevalent vertebral compression fracture in the late postmenopausal
group was independently associated with cardiovascular death (RR = 2.0; 95% CI
1.4 to 3.3; P = 0.004). CONCLUSION: Low bone mineral content at the menopause is
a risk factor for increased mortality in later life, especially from
cardiovascular disease.
PMID- 10190375
TI - The association of chronic cough with the risk of myocardial infarction: the
Framingham Heart Study.
AB - PURPOSE: A persistent inflammatory response accompanying chronic infections may
contribute to the risk of coronary atherothrombosis. Recent studies have reported
an association between chronic respiratory infections and an increased risk of
coronary heart disease; however, these reports have not accounted for important
confounders such as impaired lung function. METHODS: We considered chronic cough
as an indicator of chronic lung infection or inflammation in the original
Framingham Heart Study participants aged 47 to 89 years. Chronic cough was
defined as a cough present for at least 3 months in the preceding year and was
categorized as either nonproductive or productive. The association of chronic
cough with myocardial infarction was examined for six consecutive examination
cycles (1965 to 1979) among participants free of myocardial infarction at the
baseline examination. In a secondary analysis, plasma fibrinogen levels were
measured during examination cycle 10 (1965 to 1967) in a subgroup of the study
sample (n = 1,288). Multivariable logistic regression analysis was performed
adjusting for age, gender, smoking status, forced vital capacity, and other known
risk factors. RESULTS: The cross-sectional pooling method yielded 15,656 person
examinations in 3,637 subjects. During follow-up, there were 291 incident
myocardial infarctions. Chronic nonproductive cough (odds ratio [OR] 1.8, 95%
confidence interval [CI] 1.1 to 2.8) and chronic productive cough (OR 1.6, CI 1.1
to 2.4) were independent predictors of myocardial infarction. Results were
unchanged when we further adjusted for a history of heart failure. Adjusted
plasma fibrinogen levels (mean +/- SD) were greater in those with chronic
nonproductive cough than among those without cough (3.2 +/- 0.6 g/L versus 2.9 +/
0.6 g/dL, P = 0.001). CONCLUSIONS: These findings provide evidence that chronic
cough, a clinical manifestation of pulmonary infection or chronic inflammation,
is associated with the risk of myocardial infarction. Acute phase reactants such
as plasma fibrinogen may be implicated in this association. Prospective serologic
studies of infections as predictors of coronary heart disease risk are warranted.
PMID- 10190376
TI - Performance and potential impact of a chest pain prediction rule in a large
public hospital.
AB - PURPOSE: To evaluate the performance of a previously validated prediction rule
for patients presenting to the emergency department with chest pain and the
potential impact of the rule on triage decisions. SUBJECTS AND METHODS: In a
prospective cohort study, physician investigators interviewed consecutive
patients admitted for suspected acute ischemic heart disease (n = 207) by
emergency department attending physicians who had not used the prediction rule.
We measured the accuracy of the rule in predicting cardiac complications in these
patients, and compared actual triage decisions with those that might have been
recommended by use of the prediction rule. We also measured comorbid illnesses
among patients stratified as very low risk by the prediction rule, as well as the
effect of standardizing the definition of unstable angina and interpretation of
electrocardiograms (ECG) on the rule's sensitivity and specificity. RESULTS:
Overall, the rate of major cardiac complications (4.3%) was similar to that
reported in the original study (3.6%). The prediction rule performed well in
predicting these complications in our patients (area under receiver operating
characteristic curve 0.84 versus 0.80 in the original study; difference 0.04, 95%
confidence interval [CI] -0.07, 0.14). Standardized definitions of unstable
angina and interpretation of ECGs improved the specificity of the prediction rule
in predicting complications (55% versus 47%; difference 8%, 95% CI 1.5%, 13.7%).
The prediction rule recommended admission to telemetry units in 65 fewer patients
than actually occurred (31% of the entire cohort). None of these patients had
major complications. A substantial minority of "very low risk" patients (27%) had
comorbid illnesses requiring inpatient treatment. CONCLUSIONS: This independent
validation of the prediction rule suggests that it can improve triage decisions
for patients admitted with suspected acute ischemic heart disease. Additional
studies are needed to test prospectively the performance of the prediction rule
in actual decision making, its acceptance by clinicians, and its cost
effectiveness.
PMID- 10190377
TI - A randomized trial of short-course ciprofloxacin, ofloxacin, or
trimethoprim/sulfamethoxazole for the treatment of acute urinary tract infection
in women. Ciprofloxacin Urinary Tract Infection Group.
AB - PURPOSE: Bladder infections are very common in otherwise healthy women, and short
course antimicrobial treatment appears effective for many episodes of cystitis.
This study reports the results of short-course ciprofloxacin, ofloxacin, and
trimethoprim/sulfamethoxazole therapy. PATIENTS AND METHODS: We performed a
randomized, double-blind study of the efficacy and safety of a 3-day course of
oral ciprofloxacin 100 mg twice daily, ofloxacin 200 mg twice daily, or
trimethoprim/sulfamethoxazole 160/800 mg twice daily in women with acute,
uncomplicated, symptomatic lower urinary tract infection. RESULTS: A total of 866
patients were enrolled, of whom 688 (79%) were evaluated for the efficacy of
treatment (229 treated with ciprofloxacin, 228 treated with
trimethoprim/sulfamethoxazole, and 231 treated with ofloxacin). The most frequent
reason for exclusion was the failure to identify a pretreatment pathogen. The
most commonly isolated pathogen was Escherichia coli (81%). Eradication of the
pretreatment pathogen at the end of therapy occurred in 94% of ciprofloxacin, 93%
of trimethoprim/sulfamethoxazole, and 97% of ofloxacin-treated patients. At
follow-up evaluation at 4 to 6 weeks, recurrence rates (relapse or reinfection)
were 11% in the ciprofloxacin, 16% in the trimethoprim/sulfamethoxazole, and 13%
in the ofloxacin treatment group. Clinical success at the end of therapy was 93%
in the ciprofloxacin, 95% in the trimethoprim/sulfamethoxazole, and 96% in the
ofloxacin treatment groups. The frequency of all adverse events was 31% for
ciprofloxacin, 41% for trimethoprim/sulfamethoxazole, and 39% for ofloxacin
treated patients (P = 0.03). Premature discontinuation of study drug due to an
adverse event was more common in trimethoprim/sulfamethoxazole-treated patients
(n = 9) compared with those given ciprofloxacin (n = 2) or ofloxacin (n = 1; P =
0.02). CONCLUSION: Ciprofloxacin, ofloxacin, and trimethoprim/sulfamethoxazole
had similar efficacy when given for 3 days to treat acute, symptomatic,
uncomplicated lower urinary tract infection in women.
PMID- 10190378
TI - Does the survival advantage of nonwhite dialysis patients persist after case mix
adjustment?
AB - PURPOSE: Nonwhite dialysis patients survive longer than white patients; however,
their clinical characteristics differ. We examined whether case mix differences
explain the apparent survival advantage of nonwhite dialysis patients. SUBJECTS
AND METHODS: We performed a prospective cohort study using data from the US Renal
Data System Case Mix Severity Study that included 4,797 randomly selected
dialysis patients 20 years of age and older who were followed up for up to 6
years. Demographic, comorbidity, laboratory, nutritional, and functional status
data were obtained. Multivariable proportional hazards models adjusted for case
mix differences between nonwhite and white dialysis patients. Additional analyses
examined the effects of differences in transplantation rates, withdrawal from
dialysis rates, and treatment modality selection. RESULTS: Unadjusted survival
rates of black, Native American, and Asian or Pacific Islander dialysis patients
were similar, and better than that for white dialysis patients. Relative to
whites, the unadjusted relative risk (RR) for mortality among nonwhite patients
was 0.64 (95% confidence interval [CI]: 0.58 to 0.70). Adjustment for case mix
reduced, but did not eliminate, the survival advantage associated with nonwhite
race (RR = 0.78, CI: 0.71 to 0.86). Adjustment for differences in transplantation
rates (RR = 0.83, CI: 0.75 to 0.91), withdrawal from dialysis rates (RR = 0.81,
CI: 0.73 to 0.90), and initial treatment modality (RR = 0.79, CI: 0.71 to 0.87)
did not explain the lower mortality among nonwhites. CONCLUSIONS: A survival
advantage for nonwhite dialysis patients persists after case mix adjustment.
Future studies should explore additional physiologic and socioeconomic factors
that might explain this difference.
PMID- 10190379
TI - Neuroglycopenic and other symptoms in patients with insulinomas.
AB - PURPOSE: To characterize neuroglycopenic symptoms in the clinical presentation of
patients with insulinomas. SUBJECTS AND METHODS: Patients with histologically
confirmed islet cell adenomas or carcinomas were identified at a single
institution. Patient symptoms and clinical features of the insulinomas were
obtained by retrospective medical record review with special attention to
neuroglycopenic and autonomic symptoms. RESULTS: Of the 59 patients, 51% were
female. Patients' ages ranged from 17 to 79 years (median 55) at the time of
surgery. The interval from the onset of symptoms to diagnosis ranged from 1 month
to 30 years (median 24 months). Most patients were diagnosed within 1 to 5 years
(53%). Prior diagnoses included neurologic disorders (64%), especially seizure
disorders (39%); 7 (12%) patients were treated with antiseizure medications. All
patients had neuroglycopenic symptoms including confusion (83%) and personality
change or bizarre behavior (64%). Amnesia for hypoglycemia was common (41%).
Autonomic symptoms (83%) were usually diaphoresis (69%) or tremulousness (24%).
Food ingestion relieved symptoms in 71% of patients; 39% reported weight gain.
CONCLUSIONS: Despite improving diagnostic techniques, the diagnosis of an
insulinoma is often delayed. Careful inquiry about neuroglycopenic symptoms from
patients and persons who know them well is necessary whenever hypoglycemia due to
endogenous hyperinsulinemia is a clinical consideration. A history of
neuroglycopenic symptoms should suggest the diagnosis of hypoglycemia associated
with a hyperinsulinemic state.
PMID- 10190380
TI - Smoking, smoking cessation, and risk of hip fracture in women.
AB - PURPOSE: To examine the effects of cigarette smoking and smoking cessation on the
risk of hip fracture in women. PATIENTS AND METHODS: We studied 116,229 female
nurses, 34 to 59 years of age at baseline in 1980, who were followed for up to 12
years. Smoking habits and the occurrence of incident hip fractures (n = 377) due
to low or moderate trauma were self-reported on biennial mailed questionnaires.
RESULTS: Compared with women who had never smoked, the age-adjusted relative risk
(RR) of hip fracture among current smokers was 1.3 (95% confidence interval [CI]
1.0 to 1.7). The risk of hip fracture increased linearly (P = 0.09) with greater
cigarette consumption (RR = 1.6, 95% CI 1.1 to 2.3 for 25 or more cigarettes per
day). These associations were somewhat reduced by adjusting for other risk
factors for osteoporosis (menopausal status, use of postmenopausal estrogen,
physical activity, and intakes of calcium, alcohol, and caffeine): RR = 1.2, 95%
CI 0.8 to 1.3 for all current smokers; RR = 1.4, 95% CI 0.9 to 2.1 for 25 or more
cigarettes per day. Relative risks were further reduced when body mass index was
added to the model. There was no apparent benefit from quitting smoking until 10
years after cessation. After 10 years, former smokers had a reduced risk of hip
fracture (adjusted RR = 0.7, 95% CI 0.5 to 0.9) compared with current smokers.
CONCLUSION: Smokers are at increased risk of hip fracture and their risk rises
with greater cigarette consumption. Risk declines among former smokers, but the
benefit is not observed until 10 years after cessation. Both the increased risk
among current smokers and the decline in risk after smoking cessation are in part
accounted for by differences in body weight.
PMID- 10190381
TI - Long-term renal sodium handling in patients with cirrhosis treated with
transjugular intrahepatic portosystemic shunts for refractory ascites.
AB - PURPOSE: The long-term effects of transjugular intrahepatic portosystemic shunts
on renal sodium excretion are not known. We sought to determine these long-term
effects, as well as to measure the effects of a sodium load in patients who are
free of ascites. SUBJECTS AND METHODS: Ten patients with cirrhosis who had been
successfully treated with transjugular intrahepatic portosystemic stent shunt for
refractory ascites were studied before the shunt and again at 6 and 14 months
after the shunt while on a 22 mmol sodium/day diet. At 14 months they were also
studied on a 200 mmol sodium/day diet for 7 days without diuretics. Renal sodium
handling, central blood volume, neurohumoral factors, and hepatic function were
measured. RESULTS: Sodium balance was negative at 6 months (urinary sodium
excretion [mean +/- SD] 51 +/- 11 mmol/day versus 7 +/- 2 mmol/day pre-shunt; P <
0.05), was maintained at 14 months (22 +/- 4 mmol/day; P < 0.05 versus pre
shunt), and was associated with normalization of renin activity and aldosterone
levels, but not norepinephrine levels, as well as significantly improved renal
hemodynamic measurements. Sodium loading with 200 mmol/day resulted in weight
gain associated with increased central blood volume and appropriate renal sodium
handling in most but not all patients (urinary sodium excretion 188 +/- 14
mmol/day), despite persistent nonsuppressibility of sympathetic hyperactivity.
CONCLUSIONS: In cirrhotic patients with refractory ascites treated with a
transjugular intrahepatic portosystemic stent shunt, long-term renal sodium
handling is improved. Adequate intravascular filling in ascites-free cirrhotic
patients with normal portal pressure permits an improved but not normalized renal
response to a sodium load, possibly due to persistently elevated sympathetic
activity. Therefore, these patients should increase their sodium intake
cautiously.
PMID- 10190382
TI - Postexposure prophylaxis for human immunodeficiency virus (HIV) infection
following sexual assault.
AB - Although the 1998 Centers for Disease Control and Prevention's guidelines for
treatment of sexually transmitted diseases recommend offering postexposure
prophylaxis for human immunodeficiency virus (HIV) infection following sexual
assault, there are no detailed protocols on how to provide this treatment.
Postexposure prophylaxis has been shown to lower the risk of seroconversion
following occupational exposure to HIV by 81%, but has not yet been evaluated
following sexual exposure. Though scientific data are limited, victims of sexual
assault should be given the best information available to make an informed
decision regarding postexposure prophylaxis. When the choice is made to take
medications to prevent HIV infection, treatment should be initiated as soon as
possible, but no later than 72 hours following the assault, and should be
continued for 28 days. HIV postexposure prophylaxis should be provided in the
context of a comprehensive treatment and counseling program that recognizes the
physical and psychosocial trauma experienced by victims of sexual assault.
PMID- 10190383
TI - Prostatitis and urinary tract infection in men: what's new; what's true?
AB - Urinary tract and prostatic infections are common in men, and most are treated by
primary providers. Acute bacterial prostatitis is caused by uropathogens,
presents with a tender prostate gland, and responds promptly to antibiotic
therapy. Chronic bacterial prostatitis is a subacute infection, may present with
a variety of pelvic pain and voiding symptoms, and is characterized by recurrent
urinary tract infections. Effective treatment may be difficult and requires
prolonged antibiotic therapy. Nonbacterial prostatitis and chronic pelvic pain
syndrome are more common than bacterial prostatitis, and their etiologies are
largely unknown. Treatment for both nonbacterial disorders is primarily
symptomatic. An underlying anatomic or functional condition usually complicates
urinary tract infections in men, but uncomplicated infections occur, often
related to sexual activity. Gram-negative bacilli cause most urinary tract and
prostate infections. Therapy for prostatic infections requires an agent that
penetrates prostatic tissue and secretions, such as trimethoprim-sulfamethoxazole
or, preferably, a fluoroquinolone. Duration of antibiotic therapy is typically 1
to 2 weeks for cystitis, 4 weeks for acute bacterial prostatitis, and 6 to 12
weeks for chronic bacterial prostatitis. Long-term suppressive antibiotic therapy
and nonspecific measures aimed at palliation may be useful in selected patients
with recurrent bacteriuria or persistent symptoms of chronic bacterial
prostatitis.
PMID- 10190384
TI - The effectiveness of endoscopy in the management of dyspepsia: a qualitative
systematic review.
AB - PURPOSE: Dyspepsia is a common primary care condition, yet its optimal management
is poorly defined. We reviewed the literature to answer the following questions
about patients with dyspepsia: 1) Does endoscopy result in improved patient
outcomes? 2) Does endoscopy result in a reduction in the use of subsequent
medical resources? 3) Does endoscopy result in improved medical decision making?
4) Is endoscopy cost effective? METHODS: We performed a systematic review of
English-language articles in the MEDLINE, HEALTHSTAR, and EMBASE computerized
bibliographic databases from January 1985 to July 1998. We included all studies,
including decision analyses, with information about the effectiveness of
endoscopy, as measured by its impact on patient outcomes, resource utilization,
clinical decision making, or cost effectiveness. Two independent reviewers
abstracted data from each study, and assessed its methodologic quality. RESULTS:
Twenty-one studies met the inclusion criteria. For 3 of the 4 clinical questions,
the weight of evidence does not support the effectiveness of endoscopy. The
largest randomized clinical trial comparing endoscopy with empiric therapy
demonstrates equivalent symptoms and quality of life at 1 year, with increased
patient satisfaction and lower costs for initial endoscopy. Suboptimal study
design, including lack of appropriate comparison groups, limit studies measuring
the impact of endoscopy on resource utilization and decision-making. Decision
analyses indicate that noninvasive H pylori testing followed by anti-H pylori
therapy or empiric antisecretory therapy is more cost effective than initial
endoscopy. CONCLUSIONS: With the exception of one randomized clinical trial, the
preponderance of available data does not support the effectiveness of endoscopy
in the management of dyspepsia. Prospective clinical trials that evaluate patient
outcomes and resource utilization, and take H pylori status into account, are
needed to determine the effectiveness of endoscopy in the management of
dyspepsia.
PMID- 10190385
TI - Renal manifestations of hepatitis C infection.
AB - Hepatitis C is an important cause of renal disease, and renal complications may
be the presenting manifestation of hepatitis C infection. About half of patients
present with evidence of renal insufficiency, and up to one quarter present with
nephrotic syndrome. Others present with proteinuria or evidence of diminished
renal function. The pathogenesis of hepatitis C-associated renal disease remains
incompletely defined, but most evidence suggests that glomerular injury results
from deposition of circulating immune complexes in the subendothelium and
mesangium. Membranoproliferative glomerulonephritis, with or without
cryoglobulinemia, is the most common renal lesion. Interferon alpha-2b is
currently the treatment of choice. However, success is limited, with many
patients failing to respond or suffering relapse upon discontinuation of therapy.
Studies of newer treatment modalities, such as longer courses of interferon or
the use of ribavirin or immunosuppressive agents, are underway. Hepatitis C
associated renal disease may progress to end-stage renal failure requiring
dialysis in about 10% of patients.
PMID- 10190386
TI - Vitamin D resistance.
PMID- 10190387
TI - Systemic inflammatory reaction after starting highly active antiretroviral
therapy in AIDS patients treated for extrapulmonary tuberculosis.
PMID- 10190388
TI - 'dem bones, 'dem bones, 'dem dry bones.
PMID- 10190389
TI - Are associations between infection and coronary disease causal or due to
confounding?
PMID- 10190390
TI - Evaluation of risk in patients with chest pain presenting to the emergency
department.
PMID- 10190391
TI - Duodenal ulcer with bleeding as the sole symptom of relapse in ovarian carcinoma.
PMID- 10190392
TI - Reduction of homocysteine levels in coronary artery disease by low-dose folic
acid combined with vitamins B6 and B12.
AB - An increased plasma homocysteine concentration is a risk factor for
atherosclerosis. Folic acid lowers homocysteine but the optimal dose in patients
with coronary artery disease (CAD) is unclear. This placebo-controlled, single
blind, dose-ranging study evaluates the effect of low-dose folic acid on
homocysteine levels in 95 patients aged 61 +/- 11 years (mean +/- SD) with
documented CAD. Patients in each group were given either placebo or 1 of 3 daily
supplements of folic acid (400 microg, 1 mg, or 5 mg) for 3 months. Each active
treatment arm also received 500 microg vitamin B12 and 12.5 mg vitamin B6. Total
plasma homocysteine levels were measured after 30 and 90 days. Folic acid 400
microg reduced homocysteine levels from 13.8 +/- 8.8 to 9.6 +/- 2.0 micromol/L at
90 days (p = 0.001). On 1- and 5-mg folic acid, levels decreased from 13.0 +/-
6.4 to 9.8 +/- 4.0 micromol/L (p = 0.001) and from 14.8 +/- 6.9 to 9.7 +/- 3.3
micromol/L (p < 0.001), respectively. The decrease was similar in all treatment
groups. There was no significant change with placebo. Although the sample size is
small, these findings suggest that daily administration of 400 microg/day folic
acid combined with vitamin B12 and vitamin B6 may be equivalent to higher doses
in reducing homocysteine levels in patients with CAD.
PMID- 10190393
TI - Combined historical and electrocardiographic timing of acute anterior and
inferior myocardial infarcts for prediction of reperfusion achievable size
limitation.
AB - The historical time of acute symptom onset is not always an accurate indication
of the timing of onset of an acute myocardial infarction (AMI). Consideration of
electrocardiographic (ECG) timing parameters could supplement historical timing
alone as a clinical guide for decisions regarding the use of reperfusion therapy.
Three hundred ninety-five patients from 4 trials of thrombolytic therapy
conducted in the northwestern United States and western Canada are included in
the present study. A total of 316 patients received either streptokinase or
tissue plasminogen activator, and 79 received no reperfusion therapy. Historical
time of symptom onset was acquired by emergency or cardiology department
personnel and recorded on patient report forms. An ECG method for estimating the
timing of the AMI, the Anderson-Wilkins (AW) acuteness score, was calculated from
the initial standard 12-lead recording by investigators blinded to the knowledge
of symptom duration or any other study variables. Tomographic thallium-201
imaging 7 weeks after hospital admission was used to measure final AMI size. The
ECG timing method achieved a relation with final AMI size similar to that
previously reported for historical timing. The AW acuteness score proved most
useful for anterior AMI location when there was a > or = 2 hour delay following
symptom onset, but was most useful for the inferior AMI location when there was a
< 2 hour delay. Despite a longer delay, patients with high AW acuteness scores
had 50% lower final anterior AMI size than those with low scores; and despite a
shorter delay, those with low ECG acuteness scores had 50% greater final inferior
AMI size than those with high scores. The AW acuteness score combined with the
historical estimation of symptom duration should provide a more accurate basis
for predicting the potential for limitation of final AMI size than either method
alone. These results could potentially provide the basis for developing a new
method for noninvasive guidance of clinical decisions regarding administration of
reperfusion therapy in the initial evaluation of patients with AMI.
PMID- 10190394
TI - Relation between the extent of coronary artery disease and tachyarrhythmias
during dobutamine stress echocardiography.
AB - Despite accumulating data regarding the safety of dobutamine stress testing, the
possible induction of tachyarrhythmias during the test remains a major concern
for physicians, particularly in patients with extensive coronary artery disease
(CAD) or left ventricular dysfunction. The aim of this study is to evaluate the
clinical, echocardiographic, and angiographic predictors of arrhythmias during
dobutamine stress testing. Dobutamine (up to 40 microg/kg/min)-atropine (up to 1
mg) stress echocardiography was performed in 286 patients (age 58 +/- 11 years,
200 men) with suspected myocardial ischemia who underwent coronary angiography
within 3 months of the test. Wall motion score index was derived using a 16
segment/4 grade score model where 1 = normal and 4 = dyskinesia. No myocardial
infarction or death occurred during the test. Ventricular and supraventricular
tachycardia occurred in 16 (6%) and 21 (7%) patients, respectively. Systolic
blood pressure decrease > or = 40 mm Hg occurred in 7 patients (2%). Significant
CAD was detected in 220 patients (77%). There was no significant difference
between patients with and without tachyarrhythmias with regard to the prevalence
of CAD (78% vs 77%) or the mean number of diseased coronary arteries (1.51 +/-
0.7 vs 1.45 +/- 0.8). Independent predictors of tachyarrhythmias by multivariate
analysis of clinical, angiographic, and echocardiographic characteristics were a
higher resting wall motion score index (p <0.01) and mole gender (p <0.05).
Independent predictors of systolic blood pressure decrease > or = 40 mm Hg were a
higher baseline systolic blood pressure (p <0.0001), a history of myocardial
infarction (p <0.0001), and a higher resting wall motion score index (p <0.01).
It is concluded that tachyarrhythmias during dobutamine stress testing are
predicted by the extent of left ventricular dysfunction but not by the presence
or the extent of CAD.
PMID- 10190395
TI - Fractal analysis of heart rate dynamics as a predictor of mortality in patients
with depressed left ventricular function after acute myocardial infarction. TRACE
Investigators. TRAndolapril Cardiac Evaluation.
AB - A number of new methods have been recently developed to quantify complex heart
rate (HR) dynamics based on nonlinear and fractal analysis, but their value in
risk stratification has not been evaluated. This study was designed to determine
whether selected new dynamic analysis methods of HR variability predict mortality
in patients with depressed left ventricular (LV) function after acute myocardial
infarction (AMI). Traditional time- and frequency-domain HR variability indexes
along with short-term fractal-like correlation properties of RR intervals
(exponent alpha) and power-law scaling (exponent beta) were studied in 159
patients with depressed LV function (ejection fraction <35%) after an AMI. By the
end of 4-year follow-up, 72 patients (45%) had died and 87 (55%) were still
alive. Short-term scaling exponent alpha (1.07 +/- 0.26 vs 0.90 +/- 0.26, p
<0.001) and power-law slope beta (-1.35 +/- 0.23 vs -1.44 +/- 0.25, p <0.05)
differed between survivors and those who died, but none of the traditional HR
variability measures differed between these groups. Among all analyzed variables,
reduced scaling exponent alpha (<0.85) was the best univariable predictor of
mortality (relative risk 3.17, 95% confidence interval 1.96 to 5.15, p <0.0001),
with positive and negative predictive accuracies of 65% and 86%, respectively. In
the multivariable Cox proportional hazards analysis, mortality was independently
predicted by the reduced exponent alpha (p <0.001) after adjustment for several
clinical variables and LV function. A short-term fractal-like scaling exponent
was the most powerful HR variability index in predicting mortality in patients
with depressed LV function. Reduction in fractal correlation properties implies
more random short-term HR dynamics in patients with increased risk of death after
AMI.
PMID- 10190396
TI - Intravenous three-dimensional coronary angiography using contrast enhanced
electron beam computed tomography.
AB - Coronary angiography remains the diagnostic standard for establishing the
presence, site, and severity of coronary artery disease (CAD). Electron beam
computed tomography (EBCT), with its 3-dimensional capabilities, is an emerging
technology with the potential for obtaining essentially noninvasive coronary
arteriograms. The purpose of this study was to (1) test the accuracy of
intravenous coronary arteriography using the EBCT to conventional coronary
arteriographic images; (2) establish the inter-reader variability of this
procedure; (3) determine the limitations due to location within the coronary
tree; and (4) identify factors that contributed to improved image quality of the
3-dimensional EBCT angiograms. Fifty-two patients underwent both EBCT angiography
and coronary angiography within 2 weeks. The coronary angiogram and the EBCT 3
dimensional images were analyzed by 2 observers blinded to the results of the
other techniques. EBCT correctly identified 43 of 55 significantly stenosed
arteries (sensitivity 78%), and correctly identified 118 of 130 of the
nonobstructed arteries, yielding a specificity of 91% (p <0.001, chi-square
analysis). The overall accuracy for EBCT angiography was 87%. Significantly more
left main and anterior descending coronary arteries were adequately visualized
than the circumflex and right coronary vessels (p = 0.003). Overall, 23 of 208
(11%) major epicardial vessels were noninterpretable by the blinded EBCT readers,
primarily due to motion artifacts caused by cardiac and respiratory motion and
poor electrocardiographic gating. The inter-reader variability was similar to
that of angiography, and its high accuracy makes this a clinically useful test.
This study demonstrates, by using intravenous contrast enhancement, that EBCT can
clearly depict the coronary artery anatomy and can permit identification of
coronary artery stenosis.
PMID- 10190397
TI - Simvastatin decreases aldehyde production derived from lipoprotein oxidation.
AB - Treatment with statins are known to lower plasma and low-density lipoprotein
(LDL) cholesterol levels with resultant prevention and regression of
atherosclerosis. It has been recently suggested that the action of the statins
may also have a direct effect on other mechanisms involved in the atherosclerotic
plaque formation. Thus, we investigated whether simvastatin could have an
antioxidant effect on plasma lipoproteins. The rate of oxidation of LDL and high
density lipoproteins (HDL) was measured by conjugated diene formation with and
without the addition of increasing concentrations of simvastatin (in vitro) and
in patients with and without treatment with simvastatin (in vivo). A strong
correlation was observed between increasing simvastatin concentration and the lag
phase, a negative correlation was observed for maximal rate and maximum diene
production in LDL samples (r2 = +0.97, p <0.0001; r2 = -0.92, p <0.0001; r2 =
0.98, p <0.0001, respectively). For HDL no clear correlation could be established
with the lag phase, but a strong negative correlation was also observed between
simvastatin concentration and maximal rate and maximum diene production (r2 =
0.69, p <0.01; r2 = -0.98, p <0.0001, respectively). After 6 hours of oxidation
the production of aldehydes in LDL and HDL was lower (30% and 5%, respectively)
in samples obtained during simvastatin therapy with respect to those obtained
without treatment. The 2,4-decadienal showed a decrease of 37% and 64% (p <0.05)
in both oxidized-LDL and oxidized-HDL particles, respectively, with simvastatin
treatment. Our findings demonstrate that simvastatin acts as an antioxidant in
lipoprotein particles and, together with its lipid-lowering properties, could
play an important role in preventing atherosclerosis.
PMID- 10190398
TI - Effect of the stromelysin-1 promoter on efficacy of pravastatin in coronary
atherosclerosis and restenosis.
AB - It has proved difficult to identify high-risk patients for atherosclerosis and to
determine how they might respond to medication. Recently, a common promoter
variant of the human stromelysin-1 gene has been reported, which has been shown
to affect the transcription. We investigated whether this polymorphism had any
impact on the risk of events, especially restenosis and progression of coronary
artery disease and whether the effect was modulated by treatment with
pravastatin. The stromelysin-1 genotype was determined for 496 men with coronary
artery disease and cholesterol levels between 4.0 and 8.0 mmol/L, participating
in the Regression Growth Evaluation Statin Study (REGRESS) study, a clinical
trial assessing the effect of the lipid-lowering drug pravastatin on the
progression of atherosclerosis. Patients in the placebo group with 5A6A or 6A6A
genotypes had more clinical events than patients with the 5A5A genotype (26% and
12%, respectively, p = 0.03). In the pravastatin group, the risk of clinical
events in patients with 5A6A or 6A6A genotypes was lower, compared with placebo,
whereas it was unchanged in those with a 5A5A genotype (p value for interaction:
0.038). Also, the incidence of repeat angioplasty in the placebo group was
greater in patients with the 6A6A or 5A6A genotypes, compared with 5A homozygotes
(38% and 40%, respectively, vs 11%, p = 0.09). Again, treatment substantially
reduced the incidence in heterozygotes and 6A homozygotes (0% and 15%,
respectively), whereas it was unchanged in 5A homozygotes (28%, p for
interaction: 0.002). These effects were independent of the effects of pravastatin
on the lipid levels. Thus, this study suggests that the stomelysin-1 promoter
polymorphism confers a genotype-specific response to medication in determining
clinical event-free survival and the risk for symptom-driven repeat angioplasty.
This variant may therefore act as a predictor, not only of disease progression,
but also of response to therapy and risk of restenosis.
PMID- 10190399
TI - Outcome of target sites escaping high-grade (>70%) restenosis after percutaneous
transluminal coronary angioplasty.
AB - This study examined the fate of target sites that escaped high-grade restenosis
(> or = 70% diameter narrowing) after percutaneous transluminal coronary
angioplasty. Although favorable long-term prognosis after successful percutaneous
transluminal coronary angioplasty is well documented, little is known about the
stability of target sites. Long-term follow-up (mean 6.5 years, range 1.0 to
12.0) was performed in 693 patients with 948 narrowings (stenosis <70% in
diameter at follow-up coronary angiography). Among them, 249 patients (36%) with
303 target sites received late follow-up coronary angiography. The relation of
target sites to the culprit lesions for coronary events or newly developed angina
was angiographically reviewed and progression/regression was also examined,
focusing on the target sites. Regression was observed in 16 of 255 target sites
in subjects with <50% stenosis and in 21 of 48 sites in the group with midgrade
stenosis of 50% to 69% luminal narrowing (16 of 255, 6.3% vs 21 of 48, 43.8%, p
<0.001). Progression was observed in 33 and 4 sites (33 of 255, 12.9% vs 4 of 48,
8.3%; p = NS) in each group, respectively. The rest remained within the same
range of stenosis. Culprit lesions for 2 acute myocardial infarctions, 7 unstable
anginas, and 17 newly developed anginas were related to the original target
sites. Three lesions developed in the midgrade stenosis group. Those 26 lesions
were a component of 8.6% of 303 angiographically confirmed sites and 2.7% of
total target sites. Target sites that escape high-grade restenosis frequently
regress and become stable plaques and rarely trigger coronary events.
PMID- 10190400
TI - Clinical and angiographic predictors of recurrent restenosis after percutaneous
transluminal rotational atherectomy for treatment of diffuse in-stent restenosis.
AB - Due to the widespread use of stents in complex coronary lesions, stent restenosis
represents an increasing problem, for which optimal treatment is under debate.
"Debulking" of in-stent neointimal tissue using percutaneous transluminal
rotational atherectomy (PTRA) offers an alternative approach to tissue
compression and extrusion achieved by balloon angioplasty. One hundred patients
(70 men, aged 58 +/- 11 years) with a first in-stent restenosis underwent PTRA
using an incremental burr size approach followed by adjunctive angioplasty. The
average lesion length by quantitative angiography was 21 +/- 8 mm (range 5 to 68)
including 22 patients with a length > or = 40 mm. Twenty-nine patients had
complete stent occlusions with a lesion length of 44 +/- 23 mm. Baseline diameter
stenosis measured 78 +/- 17%, was reduced to 32 +/- 9% after PTRA, and further
reduced to 21 +/- 10% after adjunctive angioplasty. Primary PTRA was successful
in 97 of 100 patients. Clinical success was 97%, whereas 2 patients developed non
Q-wave infarctions without clinical sequelae. Clinical follow-up was available
for all patients at 5 +/- 4 months without any cardiac event. Angiography in 72
patients revealed restenosis in 49%, with necessary target lesion reintervention
in 35%. The incidence of rerestenosis correlated with the length of the primarily
stented segment and the length of a first in-stent restenosis. Thus, PTRA offers
an alternative approach to treat diffuse in-stent restenosis. Neointimal
debulking of stenosed stents can be achieved effectively and safely. PTRA
resulted in an acceptable recurrent restenosis rate in short and modestly diffuse
lesion, whereas the restenosis rate in very long lesions remains high despite
debulking.
PMID- 10190401
TI - Clinical and sequential angiographic follow-up six months and 10 years after
successful percutaneous transluminal coronary angioplasty.
AB - Sequential angiographic follow-up is needed for interpreting coronary events that
occur after successful percutaneous translumial coronary angioplasty (PTCA). One
hundred eight consecutive patients who had undergone successful dilatation were
followed for 10 years, and quantitative sequential angiograms were recorded at 6
months (n = 101) and 10 years (n = 68). The 10-year event rate was: 5.8 +/- 2.4%
for cardiac death, 9.7 +/- 3.3% for Q-wave acute myocardial infarction, 18.3 +/-
4.5% for additional surgery, and 22.4 +/- 4.9% for repeated angioplasty. Using
Cox's proportional-hazards regression, multivessel coronary artery disease (CAD)
(RR 5.6; 95% confidence intervals [CI] 1.2 to 24.7; p = 0.02), restenosis within
6 months (RR 7.8; 95% CI 3.1 to 20.0; p = 0.0001), and CAD progression over 10
years (RR 10.6; 95% CI 1.3 to 87.1; p = 0.004) were the strongest predictors of
all-cause death, repeated PTCA, and additional surgery, respectively, after
controlling for age and coronary risk factors. The minimal luminal diameter of 48
narrowings with complete sequential angiographic follow-up and without restenosis
remained stable from 6 months (2.13 +/- 0.60 mm) to 10 years (2.18 +/- 0.61 mm).
Disease progression was similar in nondilated arteries and dilated arteries (32%
vs 30%). The 10-year risk of coronary events was higher in patients with baseline
multivessel CAD than in those with 1-vessel CAD because of more frequent
progression of CAD (RR 3.8; 95% CI 1.6 to 6.8; p = 0.001). Thus, early cardiac
events after successful PTCA were related to restenosis, and late events to CAD
progression. Nevertheless, after the restenosis period, the target lesion
remained stable for the next 10 years. Coronary disease progression was not
related to the angioplasty procedure.
PMID- 10190402
TI - Reduction of restenosis by vessel size adapted percutaneous transluminal coronary
angioplasty using intravascular ultrasound.
AB - Restenosis following percutaneous transluminal coronary angioplasty (PTCA)
remains a serious problem in interventional cardiology. Recent trials using stent
implantation have proposed a reduction in restenosis, presumably due to a higher
initial luminal gain. This study was conducted to evaluate if the short- and long
term results following conventional PTCA may be favorable, if balloon dilation
was performed according to measurements gained by intravascular ultrasound (IVUS)
(vessel size adapted PTCA). The use of intracoronary stents might be omitted if
comparable long-term results could be achieved by this modified technique of
balloon angioplasty. This unicenter and nonrandomized pilot trial was initiated
in January 1995 with 252 patients who had 271 lesions. IVUS was performed before
and after intervention to determine the external elastic membrane (EEM) diameter
at the lesion site. The balloon catheter was sized according to the EEM diameter
measured by IVUS (EEM 10%). The mean balloon diameter was 4.1 +/- 0.5 mm, the
dilation time 130 +/- 60 seconds with a balloon pressure of 7.0 +/- 2.0 atm.
Clinical acute and 1-year long-term follow-up were obtained for all patients and
follow-up angiography in 71% of patients. Acute events occurred
postinterventionally in 5 patients (2%). The cumulative event rate during long
term follow-up was 14%. The angiographic restenosis rate (diameter stenosis >50%)
after 1 year was 19%. Vessel size adapted PTCA using IVUS led to favorable acute
and long-term results with a low restenosis rate and a low 1-year clinical event
rate. Despite dissections that occur frequently using large balloon sizes, an
increased rate of major complications did not occur, indicating a safe procedure
and substantiating the philosophy of "therapeutic dissections." The results need
to be verified in a randomized trial.
PMID- 10190403
TI - Heart rate dynamics before spontaneous onset of ventricular fibrillation in
patients with healed myocardial infarcts.
AB - The traditional methods of analyzing heart rate (HR) variability have failed to
predict imminent ventricular fibrillation (VF). We sought to determine whether
new methods of analyzing RR interval variability based on nonlinear dynamics and
fractal analysis may help to detect subtle abnormalities in RR interval behavior
before the onset of life-threatening arrhythmias. RR interval dynamics were
analyzed from 24-hour Holter recordings of 15 patients who experienced VF during
electrocardiographic recording. Thirty patients without spontaneous or inducible
arrhythmia events served as a control group in this retrospective case control
study. Conventional time- and frequency-domain measurements, the short-term
fractal scaling exponent (alpha) obtained by detrended fluctuation analysis, and
the slope (beta) of the power-law regression line (log power - log frequency, 10(
4)-10(-2) Hz) of RR interval dynamics were determined. The short-term correlation
exponent alpha of RR intervals (0.64 +/- 0.19 vs 1.05 +/- 0.12; p <0.001) and the
power-law slope beta (-1.63 +/- 0.28 vs -1.31 +/- 0.20, p <0.001) were lower in
the patients before the onset of VF than in the control patients, but the SD and
the low-frequency spectral components of RR intervals did not differ between the
groups. The short-term scaling exponent performed better than any other
measurement of HR variability in differentiating between the patients with VF and
controls. Altered fractal correlation properties of HR behavior precede the
spontaneous onset of VF. Dynamic analysis methods of analyzing RR intervals may
help to identify abnormalities in HR behavior before VF.
PMID- 10190404
TI - Effects of combination antihypertensive therapy on baroreflex sensitivity and
heart rate variability in systemic hypertension.
AB - Earlier studies have shown that cardiovascular autonomic regulation is impaired
in untreated or poorly controlled systemic hypertension. The purpose of this
double-blind, randomized parallel trial was to evaluate whether improved blood
pressure (BP) control can reverse this impairment. The study group consisted of
33 patients (age 45 to 63 years) with poor BP control who received randomized
metoprolol or enalapril monotherapy. Baroreflex sensitivity (BRS) was assessed by
phenylephrine test and time- and frequency-domain measurements of heart rate
variability (HRV) were analyzed from 24-hour ambulatory electrocardiographic
recordings during monotherapy and after 10 weeks of combination therapy with
metoprolol + felodipine or enalaril + hydrochlorothiazide to lower casual BP to <
140/90 mm Hg. Intensified treatment decreased 24-hour systolic and diastolic BP
from 139 +/- 12/86 +/- 8 mm Hg to 126 +/- 8/80 +/- 7 mm Hg (p <0.0001). BRS
improved from 6.2 +/- 3.2 ms/mm Hg to 8.9 +/- 4.1 ms/mm Hg (p <0.0001) and
measurements of HRV (e.g., SD of all RR intervals from 128 +/- 45 ms to 145 +/-
46 ms, p <0.001) improved significantly during the combination therapy. Changes
in BRS and HRV were similar in magnitude in both treatment arms. Mean RR
intervals were comparable before and after intensive antihypertensive therapy
(850 +/- 124 ms vs 937 +/- 279 ms, p = NS). These data indicate that adequate BP
control with modem antihypertensive combination therapy can improve
cardiovascular autonomic function, which may partially explain the reduced
cardiac mortality observed in patients with intensified antihypertensive therapy.
PMID- 10190405
TI - Cost effectiveness of carvedilol for heart failure.
AB - In this study, we examine the cost effectiveness of carvedilol for the treatment
of chronic heart failure (CHF). We use a Markov model to project life expectancy
and lifetime medical care costs for a hypothetical cohort of patients with CHF
who were assumed alternatively to receive carvedilol plus conventional therapy
(digoxin, diuretics, and angiotensin-converting enzyme inhibitors) or
conventional therapy alone. Patients on carvedilol were assumed to experience a
reduced risk of death and hospitalization for CHF, which is consistent with
findings from the US Carvedilol Heart Failure Trials Program. The benefits of
carvedilol were projected under 2 alternative scenarios. In the first ("limited
benefits"), benefits were conservatively assumed to persist for 6 months, the
average duration of follow-up in these clinical trials, and then end abruptly. In
the other ("extended benefits"), they were arbitrarily assumed to persist for 6
months and then decline gradually over time, vanishing by the end of 3 years. We
estimated our model using data from the US Carvedilol Heart Failure Trials
Program and other sources. For patients receiving conventional therapy alone,
estimated life expectancy was 6.67 years; corresponding figures for those also
receiving carvedilol were 6.98 and 7.62 years under the limited and extended
benefits scenarios, respectively. Expected lifetime costs of CHF-related care
were estimated to be $28,756 for conventional therapy, and $36,420 and $38,867
for carvedilol (limited and extended benefits, respectively). Cost per life-year
saved for carvedilol was $29,477 and $12,799 under limited and extended benefits
assumptions, respectively. The cost effectiveness of carvedilol for CHF compares
favorably to that of other generally accepted medical interventions, even under
conservative assumptions regarding the duration of therapeutic benefit.
PMID- 10190406
TI - Prevalence and clinical determinants of mitral, tricuspid, and aortic
regurgitation (the Framingham Heart Study)
AB - Little information is available on the prevalence and determinants of valvular
regurgitation in the general population. This study sought to assess the
prevalence and clinical determinants of mitral (MR), tricuspid (TR), and aortic
(AR) regurgitation in a population-based cohort. Color Doppler echocardiography
was performed in 1,696 men and 1,893 women (aged 54 +/- 10 years) attending a
routine examination at the Framingham Study. After excluding technically poor
echocardiograms, MR, TR, and AR were qualitatively graded from trace to severe.
Multiple logistic regression analysis was used to examine the association of
clinical variables with MR and TR (more than or equal to mild severity) and AR
(more than or equal to trace severity). MR and TR of more than or equal to mild
severity was seen in 19.0% and 14.8% of men and 19.1% and 18.4% of women,
respectively, and AR of more than or equal to trace severity in 13.0% of men and
8.5% of women. The clinical determinants of MR were age (odds ratio [OR] 1.3/9.9
years, 95% confidence interval [CI] 1.2 to 1.5), hypertension (OR 1.6; 95% CI 1.2
to 2.0), and body mass index (OR 0.8/4.3 kg/m2; 95% CI 0.7 to 0.9). The
determinants of TR were age (OR 1.5/9.9 years; 95% CI 1.3 to 1.7), body mass
index (OR 0.7/4.3 kg/m2; 95% CI 0.6 to 0.8), and female gender (OR 1.2; 95% CI
1.0 to 1.6). The determinants of AR were age (OR 2.3/9.9 years; 95% CI 2.0 to
2.7) and male gender (OR 1.6; 95% CI 1.2 to 2.1). A substantial proportion of
healthy men and women had detectable valvular regurgitation by color Doppler
echocardiography. These data provide population-based estimates for comparison
with patients taking anorectic drugs.
PMID- 10190407
TI - Placebo effect of pacemaker implantation in obstructive hypertrophic
cardiomyopathy. PIC Study Group. Pacing In Cardiomyopathy.
AB - This study evaluated a possible placebo effect by pacemaker implantation. The
study design was a 3-month multicenter, double-blind, randomized cross-over study
to compare the effects of atrioventricular (AV) synchronous pacing with an
optimal AV delay to inactive pacing in patients with obstructive hypertrophic
cardiomyopathy (HC). Quality of life and left ventricular (LV) outflow tract
obstruction were evaluated after the first study period in 40 patients assigned
to inactive pacing. Data were compared with the corresponding results among the
41 subjects assigned to a first study period of active pacing. During inactive
pacing, there was a significant improvement in perceived chest pain, dyspnea, and
palpitations. Moreover, LV outflow tract gradient decreased from 71 +/- 32 mm Hg
to 52 +/- 34 mm Hg (p = 0.04). In patients assigned to active pacing the
reduction of the gradient was significantly more pronounced (70 +/- 24 mm Hg to
33 +/- 27 mm Hg; p <0.0001). The difference in gradient reduction between the
groups was highly significant (p <0.00001). In the group assigned to active
pacing there was also significant improvement in perceived symptoms as well as in
alertness, the ability to be self-autonomous, and strenuous physical exercise.
The improvements in the latter were significantly greater in those paced actively
compared with patients paced inactively, whereas the changes in perceived
symptoms did not differ between groups. In conclusion, pacemaker implantation had
a placebo effect on objective and subjective parameters in this group of patients
with obstructive HC.
PMID- 10190408
TI - Diagnostic accuracy of pediatric echocardiograms performed in adult laboratories.
AB - Although cardiologists who treat adults have been evaluating pediatric patients
using echocardiography since the early 1980s, the diagnostic accuracy of such
studies has never been tested. To prospectively assess diagnostic accuracy of
pediatric echocardiograms performed in adult laboratories (adult-lab echos)
compared with evaluations of the same patients in pediatric laboratories
(pediatric-lab echos), we gathered data from 66 patients, ages 1 day to 18 years
(median 19 months), who underwent adult-lab echos in community hospitals or
private offices before evaluation by a pediatric cardiologist; subsequently, 65
underwent pediatric-lab echos in a university hospital laboratory.
Echocardiographic diagnoses were compared with (1) diagnoses proved by
catheterization or surgery (25 patients), and (2) echocardiographic diagnoses
verified by blinded duplicate-observer review (41 patients). Eighteen patients
had no cardiac disease; 42 had simple lesions, 5 had intermediate lesions, and 1
had a complex lesion. In 25 patients with 46 procedure-proven diagnoses, the most
important error per adult-lab echo was major in 11 (44%), moderate in 7 (28%),
and minor in 3 (12%); in pediatric-lab echos it was major in 0 (0%), moderate in
1 (4%), and minor in 1 (4%). In 41 patients with 62 duplicate-observer-verified
diagnoses, the most important error per adult-lab echo was major in 5 (12%),
moderate in 12 (29%), and minor in 5 (12%); pediatric-lab echos had no errors. In
35 of 66 adult-lab echos (53%), the most important error was major or moderate.
Of these, 71% were interpretive, 17% technical, and 11% both. Error incidences
were not related to patient age, study year, use of color Doppler, or complexity
of diagnoses. In 29 of these 35 patients, pediatric-lab echos resulted in altered
clinical management, including 12 surgeries and 2 averted surgeries. In 3 of the
29, delayed diagnoses were associated with fixed pulmonary vascular disease,
hypoxemic spells, and vascular collapse with severe metabolic acidosis. This
study reveals a high incidence of diagnostic errors in pediatric echocardiograms
performed in community-based adult laboratories, despite a preponderance of
patients with simple diagnoses or no heart disease.
PMID- 10190409
TI - Aortic root dilation after the Ross procedure.
AB - This study evaluated changes in neoaortic root geometry in patients who underwent
the Ross procedure. Serial postoperative echocardiographic measurements of the
neoaortic root indexed to the square root of body surface area (centimeters
divided by meters) were obtained from 30 patients (age range 3.1 to 31.4 years)
and compared with paired preoperative and immediate postoperative values. Normal
aortic root diameter Z scores were derived from root dimensions obtained from 217
healthy controls. Compared with preoperative values, an immediate stretch of the
neoaortic versus pulmonary root (annulus and sinuses of valsalva) was observed at
a mean follow-up period of 1 week. Additional aortic annular dilation from
baseline prehospital discharge values was observed at 2 to 12 months (baseline vs
follow-up annulus Z score: 1.4 vs 2.6, p <0.01, n = 16) and at 16 to 33 months
follow-up (0.8 vs 2.0, p <0.05, n = 12). In a similar fashion, there was
additional enlargement of the aortic sinus from its stretched state at hospital
discharge at 2 to 12 months (baseline vs follow-up sinus Z score: 2.0 vs 3.3, p
<0.01, n = 17) and at 16 to 33 months (1.7 vs 3.0, p <0.01, n = 13). There were
no differences in root size between 2 to 12 and 16 to 33 months after surgery.
There was a decrease in left ventricular size with no alteration in blood
pressure or degree of aortic valve regurgitation. Thus, aortic root dilation
occurs up to the first year after the Ross procedure but does not appear to
progress beyond this time.
PMID- 10190410
TI - Use of three-dimensional echocardiography for analysis of outflow obstruction in
congenital heart disease.
AB - To evaluate the feasibility and accuracy of 3-dimensional (3D) echocardiography
in analysis of left and right ventricular outflow tract (LVOT and RVOT)
obstruction, 3D echocardiography was performed in 28 patients (age 4 months to 36
years) with outflow tract pathology. Type of lesion and relation to valves were
assessed. Length and degree of obstruction were measured. Three-D data sets were
adequate for reconstruction in 25 of 28 patients; 47 reconstructions were made.
In 13 patients with LVOT obstruction, 3D echocardiography was used to study
subvalvular details in 8, valvular in 13, and supravalvular in 1. Four of these
13 patients had complex subaortic obstruction. In 12 patients with RVOT lesions,
3D echocardiography was used to study subvalvular details in 11, valvular in 12,
and supravalvular in 2. Three-dimensional reconstructions were suitable for
analysis in 100% of subvalvular LVOT, 77% valvular LVOT, 100% supravalvular LVOT,
100% subvalvular RVOT, 50% valvular RVOT, and 50% supravalvular RVOT. Twenty
patients underwent operation, and surgical findings served as morphologic control
for thirty-four 3D reconstructions (LVOT 17, RVOT 17). Operative findings
revealed an accuracy at subvalvular LVOT of 100%, valvular LVOT 90%,
supravalvular LVOT 100%, subvalvular RVOT 100%, valvular RVOT 100%, and
supravalvular RVOT 100%. Quantitative measurements could adequately be performed.
Three-D echocardiography is feasible and accurate for analyzing both outflow
tracts of the heart. Particularly, generation of nonconventional horizontal cross
sections allows a good definition of extension and severity of lesions.
PMID- 10190411
TI - Functional evaluation of extracardiac ventriculopulmonary conduits and of the
right ventricle with magnetic resonance imaging and velocity mapping.
AB - Extracardiac ventriculopulmonary conduits tend to deteriorate over time,
developing both obstruction and regurgitation. In this prospective study,
magnetic resonance imaging (MRI) was compared with Doppler echocardiography to
determine whether MRI improves the noninvasive evaluation of conduit patients.
Twenty-five patients (median age 10 years, range 2.5 to 32) were investigated 27
times with Doppler echocardiography and an MRI protocol with spin echo sequences
for morphology, velocity mapping, and multislice gradient echo technique for
right ventricular volume measuring. Cardiac catheterization data were available
in 6 patients. Echocardiography could assess the morphology of the conduits in 6
patients, whereas MRI demonstrated all conduits efficiently. Doppler
echocardiography could evaluate the occurrence of regurgitation in 18 patients
and could quantify peak velocity in 20 of the patients. A technically adequate
MRI velocity mapping was obtained in 25 patients. There was good agreement
between MRI and Doppler echocardiography in establishing or not establishing
regurgitation, but Doppler echocardiography was less reliable in evaluating the
degree of regurgitation. The correlation between peak velocity determined with
Doppler and magnetic resonance imaging was r = 0.63 [corrected]. Correlations
between catheterization pressure gradients and noninvasive techniques were r =
0.97 for magnetic resonance imaging [corrected] versus catheterization, and r =
0.86 [corrected] for Doppler versus catheterization. MRI can provide complete
information on the morphology and function of extracardiac ventriculopulmonary
conduits, as well as of the right ventricle. If the results of MRI and
echocardiography with Doppler are in agreement, heart catheterization and
angiography can be avoided, even in patients considered for conduit replacement.
PMID- 10190412
TI - Comparison of the Sideris and Amplatzer septal occlusion devices.
AB - The results of transcatheter atrial septal defect (ASD) occlusion with 2
different devices (Sideris adjustable buttoned device vs Amplatzer Septal
Occluder) were compared in 2 consecutive series of patients. Comparative outcomes
were assessed by whether a device was implanted or not, by complications and
fluoroscopy time of implantation, and by the incidence of residual shunting on
transthoracic echocardiography at follow-up. The patient and defect
characteristics were similar in both groups. Twenty-eight of 33 Sideris devices
and 37 of 39 Amplatzer devices were implanted. The fluoroscopy time for the
Amplatzer implants was 13.4 minutes (range 8 to 41) compared with 23.7 minutes
(range 11 to 60.6) for the Sideris implants (p <0.001). The complete occlusion
rate for the Amplatzer device was 93% compared with 44% for the Sideris device at
1 year (p <0.001). In conclusion, the Amplatzer device produces higher occlusion
rates of ASDs with shorter fluoroscopy times.
PMID- 10190413
TI - Different remodeling of descending thoracic aorta after acute event in aortic
intramural hemorrhage versus aortic dissection.
AB - The natural healing process of medically treated aortic dissection (AD) and
aortic intramural hemorrhage (AIH) developed in the descending thoracic aorta was
compared to test the hypothesis that absence of intimal tear and flow
communication in AIH may have different impact on the remodeling of the affected
aorta after the acute event. In 25 patients with AD and 20 with AIH involving
distal descending thoracic aorta stabilized with medical treatment, follow-up
(mean 9 months) transesophageal echocardiography was performed to measure the
maximal dimensions of aorta, true lumen, false lumen in AD, and abnormal wall
thickening in AIH. The sex ratio, prevalence of hypertension, baseline maximal
dimension, and longitudinal extent of the affected aorta did not show any
significant difference in both groups. Patients with AIH were older than those
with AD (63 +/- 10 vs 50 +/- 9, p <0.01). Disappearance of abnormal wall
thickening with complete restoration of the aorta occurred in 70% (14 of 20)
patients with AIH, which was significantly more frequent than in AD (8%, p
<0.01). In AD, progressive dilatation of the aorta with continuous flow
communication in the false lumen resulted in larger dimension of the aorta than
in AIH (44 +/- 13 vs 35 +/- 7 mm, p <0.01). Absence of persistent flow
communication resulted in a favorable remodeling process in AIH affecting distal
descending aorta. This finding, along with different mean age in AIH and AD, may
suggest that AIH is not just a precursor of overt AD but a distinct disease
entity with different pathophysiology.
PMID- 10190414
TI - Commentary on the use of run-in periods in clinical trials.
AB - Concerns have been raised about the applicability of clinicals trials to the so
called "real world" setting of clinical practice when such trials employ run-in
periods. In fact, run-in periods are an essential part of good medical practice,
and the limited practical applicability of clinical trial results relates more to
their rigid artificial protocol setting.
PMID- 10190415
TI - Comparison of the prognostic value of qualitative versus quantitative stress
tomographic perfusion imaging.
AB - This study compared qualitative assessment of exercise thallium imaging to
quantitative assessment in predicting outcome in 713 patients with 78% prevalence
of coronary artery disease by coronary angiography; during a mean follow-up of 52
months, there were 106 hard cardiac events (death or nonfatal myocardial
infarction). The qualitative method provided important prognostic information;
however, unlike the quantitative technique, less patients were assigned to either
the low- or high-risk group and proportionally more patients into the
intermediate-risk group, which may limit the clinical usefulness of the
technique.
PMID- 10190416
TI - Automated electrocardiographic scores to estimate myocardial injury size during
the course of acute myocardial infarction.
AB - The automated ST-elevation score at admission and maximal QRS score during
hospitalization provide good estimates of biochemical injury size during the
course of first myocardial infarction. Being easily computerized, such scores
could be used routinely to monitor the effect of injury-limiting therapy.
PMID- 10190418
TI - Significance of ST-segment depression with R-wave amplitude decrease on exercise
testing.
AB - A retrospective evaluation was performed of patients who underwent exercise tests
and angiography and 50 ambulatory normal subjects who underwent only exercise
testing. We found that when deltaST depression of 0.5 mm was combined with deltaR
wave decrease of 1 mm, the sensitivity and specificity were improved.
PMID- 10190417
TI - Impairment of serotonin-mediated nitric oxide release across the coronary bed in
patients with coronary spastic angina.
AB - Simultaneous assessment of plasma nitrate/nitrite and serotonin levels revealed
possible impairment of serotonin-mediated nitric oxide release in patients with
coronary spastic angina.
PMID- 10190419
TI - Evaluation of coronary revascularization to prevent tachycardia recurrences in
survivors of ventricular fibrillation.
AB - Long-term follow-up of 29 consecutive survivors of ventricular fibrillation who
underwent revascularization demonstrated that recurrent arrhythmics events were
common. Because revascularization alone does not prevent arrhythmia recurrence,
treatment with an implantable defibrillator should be considered in these
patients.
PMID- 10190420
TI - Angiographic restenosis rate in patients with chronic total occlusions and
subtotal stenoses after initially successful intracoronary stent placement.
AB - The 5-month angiographic in-stent restenosis rate did not differ between patients
with chronic total occlusions (n = 43) and subtotal stenoses (n = 43) equally
matched for diabetes status, exact stent design, final expanded stent diameter,
stent length, and residual percent diameter stenosis after stent placement; it
was 32.5% and 27.9% for those with chronic total occlusions and subtotal
stenoses, respectively (p = 0.638). Furthermore, the stent occlusion rate (4.6%
vs 6.9%, respectively) was low in both patient groups.
PMID- 10190421
TI - Efficacy of transradial primary stenting in patients with acute myocardial
infarction.
AB - We conducted a prospective observational study to assess the effectiveness of
"transradial primary stenting" in 33 patients with acute myocardial infarction,
along with acute risk stratification and accelerated patient care. With use of
adequate inclusion and exclusion criteria, the radial artery can be used as an
access site for catheterization, and transradial primary stenting can be
performed rapidly and successfully by trained coronary interventionalists.
PMID- 10190422
TI - Ramipril reduces QT dispersion in patients with acute myocardial infarction and
heart failure.
AB - In a cohort of 67 patients from the Acute Infarction Ramipril Efficacy study, we
showed that ramipril therapy was associated with a significant reduction in QT
dispersion over a 2-month period after acute myocardial infarction. This
reduction of ventricular repolarization inhomogeneity indicates an antiarrhythmic
effect and may be an important additional mechanism for the reduced all-cause
mortality and sudden death incidence achieved with angiotensin-converting enzyme
inhibition after acute myocardial infarction.
PMID- 10190423
TI - Double external direct-current shocks for refractory atrial fibrillation.
AB - Encouraged by preliminary data using double external direct-current (DC) shocks
in patients with atrial fibrillation refractory to single external DC shocks, we
undertook a prospective study of all patients with atrial fibrillation of > 1
month duration using a shock sequence with (1) 1 shock of 200 J anterior
posterior, (2) 1 shock of 360 J anterior-posterior, (3) 1 shock of 360 J apex
anterior, and (4) double shocks with configurations 2 and 3 delivered almost
simultaneously by 2 defibrillators. The double shocks appeared to be safe and
restored sinus rhythm in approximately 2 of 3 of patients in whom DC
cardioversion failed with single shocks.
PMID- 10190424
TI - Effect of cardiac pacing on peripheral and cerebral hemodynamics in patients with
carotid sinus syndrome.
AB - The effect of dual-chamber detected atrioventricular pacing mode alone and
combined with rate-drop response reduced vasodepression and cerebral
hypoperfusion induced by carotid massage in patients with carotid sinus syndrome.
PMID- 10190425
TI - Age-related changes of cardiac parasympathetic modulation after vasovagal
syncope.
AB - The time-domain analysis of 24-hour electrocardiographic recordings showed that
vagal modulation of heart rate is reduced within 48 hours from vasovagal syncope.
However, patients with recent vasovagal syncope can be differentiated from
healthy subjects only up to the age of 40 years with this analysis, because this
parasympathetic modulation physiologically decreases with increasing age.
PMID- 10190426
TI - Transcatheter coil embolization of abnormal vascular connections using a new type
of delivery catheter for enhanced control.
AB - A new type of delivery catheter, designed with a 0.033-inch distal tip that grips
a 0.038-inch Gianturco coil, was used to occlude 61 abnormal vascular connections
in 44 patients with a complete closure rate of 87%. Withdrawal (n = 6) or
repositioning (n = 2) of an inappropriately positioned coil was necessary in 8 of
44 patients, and was successfully achieved in all by the delivery catheter
without need for additional equipment.
PMID- 10190427
TI - Extrinsic compression of the left main coronary artery by the pulmonary artery in
patients with long-standing pulmonary hypertension.
AB - Left main coronary artery compression by the pulmonary artery may be seen in
patients with pulmonary hypertension who are undergoing cardiac catheterization.
Cardiac magnetic resonance imaging is useful in these patients to document
extrinsic compression, which might otherwise be mistaken for intrinsic
atherosclerotic disease.
PMID- 10190428
TI - Recognition of functional pulmonary atresia by color Doppler echocardiography.
AB - Vigorous crying aids right ventricular ejection into the pulmonary artery. This
phenomenon can differentiate functional pulmonary atresia from anatomic pulmonary
atresia.
PMID- 10190429
TI - Prospective anthropometric analysis of sagittal orbital-globe relationship
following fronto-orbital advancement in childhood.
AB - Fronto-orbital advancement is a common procedure for correction of supraorbital
retrusion in patients with coronal craniosynostosis. The aim of this study was
two-fold: to quantitate change in the sagittal orbital-globe relationship
following fronto-orbital advancement in childhood and to determine the ratio of
skeletal-to-soft tissue movement. Soft-tissue points on the orbital rim, orbitale
superius (os), orbitale laterale (ol), orbitale inferius (oi), and nasion (n),
referenced to apex corneae (ac), were measured preoperatively and postoperatively
by a custom-made anthropometer. Intraoperative bony advancement was measured with
a caliper. Patients were selected with uniform advancement at the fronto-nasal
suture and laterally at the mortise and tenon. Fifteen patients with syndromic
craniosynostosis were included in the study (six male, nine female): Apert (n =
2), Crouzon (n = 5), Pfeiffer (n = 4), Saethre-Chotzen (n = 3), and Boston type
(n = 1). Average age at operation was 8.7 years (range, 4.5 to 10.5 years). Age,
sex, method of fixation, postoperative interval, diagnosis, and skeletal movement
were analyzed for possible effect on the magnitude of soft-tissue advancement.
Average intraoperative skeletal advancement was 12.1 mm, and average
postoperative soft-tissue movement was 10.3 mm (p < 0.001), measured at the
midpoint of the supraorbital rims (os). The soft tissue: skeletal movement ratio
was 0.9:1. Os was the only point at which soft-tissue advancement could be
predicted (Spearman's rank correlation coefficient = 0.67); soft-tissue changes
at ol, oi, and n were unpredictable. Skeletal movement was the only determinant
of soft-tissue advancement of all variables tested, i.e., diagnosis, age, sex,
previous fronto-orbital advancement, and wire versus plate fixation. We make
recommendations for calculating the magnitude of fronto-orbital advancement,
based on preoperative anthropometry and a soft-to-hard tissue advancement factor.
PMID- 10190430
TI - The use of nasal splints in the primary management of unilateral cleft nasal
deformity.
AB - Primary surgical correction of the cleft lip nasal deformity is routinely
performed at the Craniofacial Center at Chang Gung Memorial Hospital. Over time,
however, there is a tendency for the lower lateral cartilage to retain its memory
and, subsequently, recreate the preoperative nasal deformity. Therefore, it is
current practice to use a nostril retainer for a period of at least 6 months to
maintain the corrected position of the nose. The aim of this study was to
qualitatively assess the benefit of postoperative nasal splinting in the primary
management of unilateral cleft nasal deformity. Data from two groups of 30
patients with complete unilateral cleft lips each were retrospectively collected
and analyzed. The first group served as a control (no nasal splints), and the
second group used the nasal retainer compliantly for at least 6 months
postoperatively. All patients had their primary lip repair at 3 months of age. A
photographic evaluation of the results when the patients were between 5 and 8
years of age was conducted. The parameters used to assess the nasal outcome were
nostril symmetry, alar cartilage slump, alar base level, and columella tilt. The
first scores were based on residual nasal deformity, and the second set were
based on overall appearance. It was found that the mean scores of residual nasal
deformity for all four parameters in patients who used the nasal stent were
statistically better than the scores of patients who did not (p values ranged
from 0.0001 to 0.005). The overall appearance scores for the four parameters in
the patients who used the nasal stent after surgery were also statistically
better than the scores for those who did not (p values ranged from 0.0001 to
0.01). The results show that postoperative nasal splinting in the primary
management of the unilateral cleft nasal deformity serves to preserve and
maintain the corrected position of the nose after primary lip and nasal
correction, resulting in a significantly improved aesthetic result. Therefore, it
is recommended that all patients undergoing primary correction of complete
unilateral cleft deformity use the nasal retainer postoperatively for a period of
at least 6 months.
PMID- 10190431
TI - The septal chondromucosal island pedicle flap: anatomic study and clinical
application.
AB - A study was made of the facial regions of 10 fresh cadavers. The vascular anatomy
of the perinasal region and the septum consistently confirmed the existence of a
nasal alar basal artery and a nasal alar basal nerve to the septum. A new septal
chondromucosal flap, supplied by the nasal alar basal artery and nerve, is
proposed in this article. The composite flap can be used safely to restore
partial or entire tarsoconjunctival defects of the upper or lower eyelid or
combined defects of the upper and lower eyelid.
PMID- 10190432
TI - Mandibular growth after distraction in patients under 48 months of age.
AB - Distraction osteogenesis is an effective technique for reconstruction of the
congenitally deficient mandible. However, the age at which it is best performed
remains under discussion. Distraction performed at an early age, while possibly
allowing the face to develop with a more normal functional matrix, may entail a
higher rate of complications. Additionally, it is possible that subsequent
asymmetric growth of the mandible may necessitate serial distraction. To address
this issue, the clinical records and cephalometric radiographs of all patients
less than 48 months of age undergoing mandibular distraction at New York
University Medical Center between August of 1989 and August of 1997 were
examined. There was a total of 14 patients ranging in age from 19 months to 43
months. Nine patients had a diagnosis of unilateral craniofacial microsomia,
three had Treacher Collins syndrome, one had Nager syndrome, and one had
bilateral developmental micrognathia. The average amount of distraction was 27 mm
(range, 23 to 39 mm) in unilateral cases and 24 mm in bilateral cases (range, 15
to 31 mm). The period of clinical follow-up averaged 32.6 months (range, 12 to 92
months). All patients showed significant improvement in craniofacial appearance,
and in four patients, long-term tracheostomy tubes were removed. There were two
major complications. In one patient with craniofacial microsomia, there was a
relapse in the early postretention phase related to the presence of a dentigerous
cyst. This required removal of the cyst and repeat distraction. In the patient
with Nager syndrome, a coronoid ankylosis developed requiring surgical release.
There were no other major complications. The scars required revision in only two
of the patients. Cephalometric analysis of the patients in the study revealed a
differential in the rate of growth between the affected and the unaffected side
in all cases of craniofacial microsomia. The affected side always grew at a
slower rate than the contralateral side after the distraction process was
complete. This led to a progressive asymmetry of the rami, clinically expressed
by some degree of facial asymmetry and an occlusal cant. For this reason,
secondary distraction was required in one patient and is planned in a second.
Initial overcorrection of the patient would seem to minimize the likelihood that
secondary distraction will be necessary. Distraction osteogenesis for
reconstruction of the mandible in this subset of young patients was a safe and
effective technique for improving the craniofacial skeletal form and appearance,
with minimal associated morbidity. Longer follow-up is necessary to assess the
full impact of growth in these cases.
PMID- 10190433
TI - Evaluation of bone height in osseous free flap mandible reconstruction: an
indirect measure of bone mass.
AB - Osseous free flaps have become the preferred method of mandibular reconstruction
after oncologic surgical ablation. To elucidate the long-term effects of free
flap mandibular reconstruction on bone mass, maintenance or reduction in bone
height over time was used as an indirect measure of preservation or loss in bone
mass. Factors potentially influencing bone mass preservation were evaluated;
these included site of reconstruction (central, body, ramus), patient age, length
of follow-up, adjuvant radiotherapy, and the delayed placement of osseointegrated
dental implants. A retrospective analysis of patients undergoing osseous free
flap mandible reconstruction for oncologic surgical defects between 1987 and 1995
was performed. Postoperative Panorex examinations were used to evaluate bone
height and bony union after osteotomy. Fixation hardware was used as a reference
to eliminate magnification as a possible source of error in measurement. There
were 48 patients who qualified for this study by having at least 24 months of
follow-up. There were 27 male and 21 female patients, with a mean age of 45 years
(range, 5 to 75 years). Mandibular defects were anterior (24) and lateral (24).
Osseous donor sites included the fibula (35), radius (6), scapula (4), and ilium
(3). There were between zero and four segmental osteotomies per patient
(excluding the ends of the graft). Nineteen percent of all patients had delayed
placement of osseointegrated dental implants. Initial Panorex examinations were
taken between 1 and 9 months postoperatively (mean, 2 months). Follow-up Panorex
examinations were taken 24 to 104 months postoperatively (mean, 47 months). The
bony union rate after osteotomy was 97 percent. Bone height measurements were
compared by site and type of reconstruction. The mean loss in fibula height by
site of reconstruction was 2 percent in central segments, 7 percent in body
segments, and 5 percent in ramus segments. The mean loss in bone height after
radial free flap mandible reconstruction was 33 percent in central segments and
37 percent in body segments; ramus segments did not lose height. The central and
body segments reconstructed with scapular free flaps did not lose height, but one
ramus segment lost 20 percent of height. There was no loss in bone height in
mandibular body reconstruction with the ilium free flap. Fibula free flaps did
not significantly lose bone height when evaluated with respect to age, follow-up,
radiation therapy, or dental implant placement. The retention in bone height
demonstrated in this study suggests that bone mass is preserved after osseous
free flap mandible reconstruction. The greatest amount of bone loss was seen
after multiply osteotomized radial free flaps were used for central mandibular
reconstruction. The ability of the fibula free flap to maintain mass over time,
coupled with its known advantages, further supports its use as the "work horse"
donor site for mandible reconstruction.
PMID- 10190434
TI - A new extended external oblique musculocutaneous flap for reconstruction of large
chest-wall defects.
AB - A new extended external oblique musculocutaneous flap utilized in the
reconstruction of chest-wall defects is described. The flap is drawn as a V-Y
rotation flap on the ipsilateral abdominal wall. It is laterally based, and its
pedicle coincides with the five lowest costal insertions of the external oblique.
The flap extends above the transiliac line, from the posterior axillary line to
the linea alba, and includes the dynamic territory of the external oblique
muscle. Vascular supply is provided by the musculocutaneous perforating arteries
of the intercostal vessels and their subcutaneous branches. The flap is raised
medially and includes the anterior sheath of the rectus. Undermining continues
between the external and the internal oblique muscles as far as the posterior
axillary line. The donor site on the abdominal wall is reinforced by the
plication of the internal oblique sheath. This flap was used in 13 patients with
major anterior chest-wall excisional defects. The mean chest-wall defect was
about 390 cm2. Marginal necrosis with distal skin loss was observed in one
patient. All other flaps healed without complications. The extended external
oblique musculocutaneous flap differs from other external oblique flaps already
described in several aspects that allow it to obtain better functional and
aesthetic results.
PMID- 10190435
TI - Versatility and reliability of combined flaps of the subscapular system.
AB - One-stage reconstructions of complex or unusually large defects frequently
require composite tissue transfers. The various components of these "chimeric"
flaps facilitate three-dimensional reconstructions or the coverage of large
surface defects. Data from 36 combined flaps from the subscapular arterial system
are demonstrated in this series. Defect locations were evenly distributed between
the upper and lower extremities. Eighty-three percent were two-component flaps,
and 17 percent contained three or more various tissue components. Overall flap
survival was 97 percent. Major complications included vascular revisions in four
patients and seven secondary skin transplantations. Five cases contained osseous
components. The independent mobility of skin, muscle, and bone proved to be a
major advantage in the reconstruction of compound defects. Donor-site morbidity
was acceptable; the most frequent donor-site complication was persistent seroma
in 9 of 36 patients (25 percent). Patient satisfaction was high. Ninety-one
percent were satisfied with the operative result and would undergo the operation
again. Eighty-six percent accepted the aesthetic appearance of the donor site.
The data demonstrate that these complex flap procedures are extremely reliable
and versatile, thus avoiding multiple reconstructive procedures and achieving
excellent reconstructive results with acceptable donor-site morbidity.
PMID- 10190436
TI - Refinement of the central pedicle breast reduction by application of the
ligamentous suspension.
AB - In a previous article, the location of the neurovascular structures inside the
breast were exactly determined using a suspension apparatus, and how to access
these structures was described. The horizontal septum originates at the level of
the fifth rib and curves upward into vertically oriented medial and lateral
ligaments, thereby guiding the main vessels and nerves to the nipple and areola.
This topographical definition is relevant to increase the precision of resection
in breast reductions. In further anatomic dissections of 20 female breasts, it
was found that the horizontal septum constantly divides the breast into regular
sections and, consequently, it can be used as a guide to achieve symmetry in
breast reductions with a central pedicle. Using it provides a more predictable
and reliable method of maintaining sensation and viability within the nipple
areola complex and attaining symmetry in both breasts. Because no dermal pedicle
is necessary, the size of the resulting scar can be reduced. The suspending
function of the ligaments provides improved ability to shape the breast. Using
this understanding of the ligamentous suspension of the breast, it has been
possible to perform safe breast resections with a central pedicle, irrespective
of the amount of resection and risk factors. This new approach has been used on
42 patients.
PMID- 10190437
TI - Reduction mammaplasty and mastopexy with superficial fascial system suspension.
AB - Classic descriptions of breast reduction and mastopexy techniques have relied on
dermal suspension with or without glandular shaping to contour the breast. Dermal
suspension is often an unreliable and inconsistent anchor for high-tension wound
repairs, resulting in unpredictable or poor scarring along with inadequate long
term lifting of the soft tissues. Hypertrophic scarring commonly occurs after
dermal suspension reduction mammaplasty, being noted in 50 to 55 percent of
patients at 6 months. Current studies regarding the anatomy and function of the
superficial fascial system (SFS) have led to multiple applications of suspension
with permanent (nonabsorbable) sutures in high-tension wound repairs of the body.
As in other areas of the body, this system can be used effectively for suspension
of breast-contouring procedures. Suturing the anterior SFS layer with
nonabsorbable sutures (separately from the breast tissue or dermis) provides
minimal tension skin repair. This should result in more predictable scarring with
reduced risk of scar widening and hypertrophy. In addition, using SFS suspension
in mammaplasties may result in longer-lasting contour results. The keyhole
pattern used for dermal suspension techniques must be modified for SFS
suspension. Reduction mammaplasty or mastopexy using these suspension wound
repair techniques was performed in 109 patients (218 breasts) with a 6- to 36
month follow-up. The incidence of hypertrophic scarring was 3 percent at 6 months
in this series. Suspension in mammaplasty procedures improved scar quality and
provided more predictable and stable breast contours over long-term follow-up.
PMID- 10190438
TI - The rectus abdominis free flap as an emergency procedure in extensive upper
extremity soft-tissue defects.
AB - Stable wound coverage after extensive soft-tissue loss of the upper extremity
remains a difficult problem in the management of large defects of the upper limb.
To prevent further tissue loss owing to infection or inadequate cover when
important structures such as vessels, tendons, nerves, joints, and bones are
exposed, various free flaps have been introduced into the therapeutic
armamentarium of acute plastic surgical management options. Emergency or delayed
early reconstruction has been proposed to prevent chronic infection and further
tissue loss. We report a series of 12 emergency and delayed early reconstructions
of the forearm, wrist, carpus, metacarpus, and hand using the free rectus
abdominis muscle flap with split-skin coverage, demonstrating the versatility of
this flap within this special context. Emergency free rectus muscle flap transfer
is safe, technically easy, and expandable.
PMID- 10190439
TI - Replantation of fingertip amputation by using the pocket principle in adults.
AB - There are several treatment modalities for zone 1 or zone 2 fingertip amputations
that cannot be replanted by using microsurgical techniques, such as delayed
secondary healing, stump revision, skin graft, local flaps, distant flaps, and
composite graft. Among these, composite graft of the amputated digit tip is the
only possible means of achieving a full-length digit with a normal nail complex.
The pocket principle can provide an extra blood supply for survival of the
composite graft of the amputated finger by enlarging the area of vascular
contact. The surgery was performed in two stages. The amputated digit was
debrided, deepithelialized, and reattached to the proximal stump. The reattached
finger was inserted into the abdominal pocket. About 3 weeks later, the finger
was removed from the pocket and covered with a skin graft. We have consecutively
replanted 29 fingers in 25 adult patients with fingertip amputations by using the
pocket principle. All were complete amputations with crushing or avulsion
injuries. Average age was 33.64 years, and men were predominant. The right hand,
the dominant one, was more frequently injured, with the middle finger being the
most commonly injured. Of the 29 fingers, 16 (55.2 percent) survived completely
and 10 (34.5 percent) had partial necrosis less than one-quarter of the length of
the amputated part. The results of the above 26 fingers were satisfactory from
both functional and cosmetic aspects. Twenty of the 29 fingers, which had been
followed up for more than 6 months (an average of 16 months), were included in a
sensory evaluation. Fifteen of these 20 fingers (75 percent) were classified as
"good" (static two-point discrimination of less than 8 mm and normal use). From
the overall results and our experience, we suggest that the pocket principle is a
safe and valuable method in replantation of zone 1 or zone 2 fingertip
amputation, an alternative to microvascular replantation, even in adults.
PMID- 10190441
TI - Long-term remodeling of vascularized and nonvascularized onlay bone grafts: a
macroscopic and microscopic analysis.
AB - The present study was performed to compare vascularized and nonvascularized onlay
bone grafts to investigate the potential effect of graft-to-recipient bed
orientation on long-term bone remodeling and changes in thickness and
microarchitectural patterns of remodeling within the bone grafts. In two groups
of 10 rabbits each, bone grafts were raised bilaterally from the supraorbital
processes and placed subperiosteally on the zygomatic arch. The bone grafts were
oriented parallel to the zygomatic arch on one side and perpendicular to the arch
on the contralateral side. In the first group, vascularized bone grafts were
transferred based on the auricularis anterior muscle, and in the second group
nonvascularized bone grafts were transferred. Fluorochrome markers were injected
during the last 3 months of animal survival, and animals were killed either 6 or
12 months postoperatively. The nonvascularized augmented zygoma showed no
significant change in thickness 6 months after bone graft placement and a
significant decrease in thickness 1 year after graft placement (p < 0.01). The
vascularized augmented zygoma showed a slight but statistically significant
decrease in thickness 6 months after graft placement (p < 0.003), with no
significant difference relative to its initial thickness 1 year after graft
placement. In animals killed 6 months after bone graft placement, both the rate
of remodeling and the bone deposition rate measured during the last 3 months of
survival were significantly higher in the vascularized bone grafts compared with
their nonvascularized counterparts (p < 0.02). By 1 year postoperatively, there
were no significant differences in thickness, mineral apposition rate, or osteon
density between bone grafts oriented perpendicular and parallel to the zygomatic
arch. These findings indicate that the vascularity of a bone graft has a
significant effect on long-term thickness and histomorphometric parameters of
bone remodeling, whereas the direction of placement of a subperiosteal graft
relative to the recipient bed has minimal effect on these parameters. In
vascularized bone grafts, both bone remodeling and deposition are accelerated
during the initial period following graft placement. Continued bone deposition
renders vascularized grafts better suited for the long-term maintenance of
thickness and contour relative to nonvascularized grafts.
PMID- 10190440
TI - The vascularized pig fibula bone flap model: effects of multiple segmental
osteotomies on growth and viability.
AB - Previous work by this laboratory introduced the pig fibula bone flap as a model
for the study of the pathophysiology of vascularized bone flaps. Anatomic and
hemodynamic studies demonstrated a significant (p < 0.05) decrease in vascular
perfusion after a series of segmental osteotomies and rigid fixation (lag screws
and miniplates) in the distal end of the flap, suggesting that blood flow to the
distal osteotomized segment of the flap may be impaired. Killing the animals
after blood flow studies precluded assessment of the effect of these hemodynamic
changes on bone healing. Therefore, the aim of this study was to assess the pig
fibula bone flap model with respect to viability, healing, and subsequent growth
after multiple segmental osteotomies and rigid fixation to contribute to the
understanding of vascularized bone flap pathophysiology. Yorkshire pigs (20 to 25
kg) were used for all experiments. Eight pigs underwent unilateral elevation of a
vascularized fibula bone flap, which was osteotomized into three segments and
orthotopically rigidly fixed using a 2.4-mm mandibular reconstruction plate. The
left fibula remained as the control. Fluorochrome labels were injected to assess
bone viability and turnover, and both fibulae were assessed for growth
radiologically. The fibulae were harvested 21 days postoperatively (when the
animals were killed), and bone healing was assessed histologically and
clinically. There were no significant differences in preoperative and
postoperative lengths of the osteotomized fibulae compared with the controls,
suggesting that there was no impairment of growth potential after multiple
segmental osteotomies and rigid fixation. Significant (p < 0.05) bony hypertrophy
of the osteotomized fibulae was noted when compared with controls. Mobility was
observed in 3 of the 32 osteotomies (9 percent), occurring across one proximal
and two distal osteotomies in association with failure of fixation. However,
histologic and fluorochrome assessment confirmed the viability of all bone
segments, as supported by the presence of tetracycline given 2 days
postoperatively. The pig fibula bone flap model is well tolerated by the pig.
Multiple segmental osteotomies and rigid fixation, previously associated with a
significant decrease in blood flow in the distal segment, did not impair either
growth potential, viability, or healing ability. It is suggested that the pig
fibula is a suitable model for the study of bone flap pathophysiology.
PMID- 10190442
TI - Auricular endochondral pseudocysts: diagnosis and management.
AB - The auricle can be the site of a variety of cystic lesions, many of which involve
either potential spaces between the auricular cartilage and the perichondrium or
spaces within the skin and subcutaneous tissues. An auricular endochondral
pseudocyst is a fluid collection located within the cartilaginous structure of
the auricle. The auricular hematoma and the auricular pseudocyst may represent
opposing ends of a continuum of damage and repair of traumatic insults. Whereas
the hematoma represents a significant acute traumatic event resulting in cleavage
between the perichondrium and the cartilage, the pseudocyst could be the outcome
of chronic lower grade trauma. In this instance, the perichondrium not only
separates from the cartilage but may be induced to regenerate an outer
cartilaginous wall exacting the contour of the separated perichondrium, thus
completing a cartilaginous auricular pseudocyst. This firm, cartilaginous outer
cyst wall accounts for the increased difficulty in treating pseudocysts and
clearly requires a different surgical treatment than for the hematoma. Having
reviewed a substantial number of case reports, we recommend incision and drainage
of the cavity followed by obliteration of the cavity by curettage, sclerosing
agent, and pressure dressing. More invasive techniques should be reserved for an
uncommon recurrence after adequate initial treatment.
PMID- 10190443
TI - Langer-Giedion syndrome associated with submucous cleft palate.
AB - We report a 4-year-old girl with characteristic features of the Langer-Giedion
syndrome (trichorhinophalangeal syndrome type II) who also had submucous cleft
palate. When she underwent a palatoplasty, a diagnosis of Langer-Giedion syndrome
was made because of the characteristic facial features, multiple exostoses, and
partial deletion of the long arm of chromosome 8. This is the first case of
trichorhinophalangeal syndrome associated with cleft palate. We review the
clinical alterations of trichorhinophalangeal syndromes and differential
diagnosis of Langer-Giedion syndrome from trichorhinophalangeal syndrome type I
and hereditary multiple exostoses. We also describe the importance of
trichorhinophalangeal syndrome in plastic surgery.
PMID- 10190444
TI - Facial resurfacing in xeroderma pigmentosum with chemical peeling.
AB - We describe our experience with two patients with xeroderma pigmentosum who
underwent multiple trichloroacetic acid chemical peels. Trichloroacetic acid and
phenol were used in one case. Until now numerous treatment modalities have been
reported. Deep chemical peeling has not been reported before in patients with
xeroderma pigmentosum. Chemical peeling is a simple procedure with less
associated morbidity.
PMID- 10190445
TI - Reconstruction of disruption of the abdominal wall in burn patients.
AB - Two patients with extensive destruction of the full thickness of the abdominal
wall and associated intra-abdominal injuries were encountered. One case resulted
from burns to a patient pinned under an automobile in contact with the muffler;
the other was injured as a result of penetration of the abdominal wall by a
railroad coupling and was also burned in an associated welding accident at the
same time. Extensive staged debridement and repair of intra-abdominal injuries in
several procedures were required in case 1. Closure was eventually achieved with
serial applications of mesh and split-thickness autografting. In case 2, an
initial attempt at flap closure failed. Coverage initially was obtained with
silicone mesh followed by split-thickness grafting. We report successful
management of two of these difficult reconstructive challenges.
PMID- 10190446
TI - Management and prevention of lumbar herniation following a latissimus dorsi flap.
AB - Lumbar herniation is a rare complication of flank surgery. We present a case of
lumbar herniation that followed the mobilization of a latissimus dorsi flap for
breast reconstruction. This is an unusual complication, which, to our knowledge,
has only been presented twice in the literature. The roles of computed tomography
for diagnosis and synthetic mesh for repair are discussed. The anatomy of the
lumbar region is reviewed, and preventative measures are discussed.
PMID- 10190447
TI - Modified Antia-Buch repair for full-thickness upper pole auricular defects.
AB - Various reconstructive techniques have been described for repair of full
thickness upper pole auricular defects. The wedge excision commonly used for
treatment of upper pole tumors allows excision and reconstruction in a single
stage. However, this technique suffers from major deficiencies. We apply the
concept of crescentic scaphal excision and the Antia-Buch advancement-rotation
flap principle to repair various full-thickness upper pole auricular defects
resulting from excision of skin lesions in eight consecutive patients. The
technique achieves a natural auricular shape in three dimensions with minimal
disruption of the anatomic landmarks and avoids conspicuous scars. It has several
advantages over the original Antia-Buch repair and other techniques used for
reconstruction of full-thickness upper pole auricular defects.
PMID- 10190448
TI - Purse-string suture for nipple projection.
AB - A simple and useful technique for nipple projection is reported. A buried,
subcutaneous, purse-string suture is placed through prick holes and, when tied,
gives a nipple mound, without the need of skin incisions, flaps, or undermining.
This procedure can be applied to inverted, missing, and/or ill-defined nipples.
PMID- 10190449
TI - Flow-through thin latissimus dorsi perforator flap for repair of soft-tissue
defects in the legs.
AB - Flow-through thin latissimus dorsi perforator flaps were used in six cases with
complicated defects of the legs. This flap has a small amount of latissimus dorsi
muscle with a considerable amount of fatty tissue removed to make a thin flap. In
addition, the flap has several branches of the subscapular vessel, which are
interposed to the recipient vessels of the legs. The advantages of this thin flap
are: (1) flow-through vascular reconstruction can preserve the main vessels of
the damaged legs; (2) the double arterial inflows and venous drainage systems of
the flap ensure safe vascularization of the flap; (3) a flow-through venous
drainage system from the distal extremities can also be established to prevent
congestion of the affected legs; (4) this flap is versatile (it can be either
thin or large); and (5) even in emergent ischemic legs, simultaneous elevation of
the flap is possible with preparation of the legs. This flow-through flap is
indicated for: (1) cases with a large skin defect and obstruction of the main
vessels in the leg; (2) cases with a possibility of tumor recurrence in the legs;
and (3) young women or girls with a large defect in the legs, rather than the
rectus abdominis musculocutaneous flap.
PMID- 10190451
TI - Rhinoplasty: a simplified, three-stitch, open tip suture technique. Part II:
secondary rhinoplasty.
AB - Tip suture techniques have proven effective in managing many secondary tip
deformities. The open approach is used in most cases because it allows analysis
and utilization of the alar remnants. If the alar rim strip is intact and not
deformed, then a three-stitch technique (strut, domal creation, and domal
equalization) is used. If the domes were previously transected, they are repaired
and an attempt is made to shape them with sutures. If sutures are ineffective or
the domes are deformed, judicious excisions and tip-shaping sutures are employed
to achieve an aesthetic "tip shape," as expressed through the overlying skin.
Removal of sutures from previously sutured tips has proven effective in the
columella and infralobular area, ineffective in the supratip midline, and
unpredictable over the domal segment. Overall, tip suture techniques should be
considered in secondary tip deformities whenever the alar cartilage remnants
permit.
PMID- 10190450
TI - Rhinoplasty: a simplified, three-stitch, open tip suture technique. Part I:
primary rhinoplasty.
AB - Tip suture techniques offer a reliable and dramatic method of tip modification
without needing to interrupt the alar rim strip or add tip grafts. The present
simplified three-stitch technique consists of the following: (1) a strut suture
to fix the columella strut between the crura, (2) bilateral domal creation
sutures to create tip definition, and (3) a domal equalization suture to narrow
and align the domes. If required, columella septal sutures can be added; either a
dorsal rotational suture or a transfixion projection suture can be used. This
simplified method represents a refinement based on more than 13 years of
experience with tip suture techniques. It does not require a complex operative
sequence or specialized sutures. Primary indications are moderate tip deformities
of inadequate definition and excessive width and certain specific tip
deformities, including the parenthesis tip and nostril/tip disproportion. The
primary contraindications are for patients with minor tip deformities that are
best done through a closed approach and those with severe tip deformities
requiring an open structure graft. The technique is simple, efficacious, and
easily learned.
PMID- 10190452
TI - A simplified algorithm for the use of Z-plasty.
AB - For the neophyte, the Z-plasty maneuver can be a surgical procedure veiled in
intrigue. The theoretical mechanics of Z-plasty geometry are described,
establishing that the new length of the central limb in a 60-degree Z-plasty is
square root(3) of its original length. Factors such as skin tension, flap
thickness, and flap location can, in application, distort the desired outcome. An
algorithm is established that describes the indications and simplifies the
execution of this technique.
PMID- 10190453
TI - Defining wetting solutions in lipoplasty.
PMID- 10190454
TI - Who's getting old?
PMID- 10190455
TI - A new educational role for plastic surgery in the fourth year of medical school.
AB - At most medical schools, students are offered limited or sporadic experiences in
plastic surgery. This is unfortunate because all physicians need to possess the
knowledge and skills to evaluate skin lesions and participate in wound
management. Also, students who are considering a career in plastic surgery do not
have adequate information to make informed decisions. With the restructuring of
plastic surgery training programs, career decisions of individuals interested in
plastic surgery are being made earlier than ever before in the education
continuum, and the aforementioned problem assumes greater magnitude both for the
students and the faculty. At MCP-Hahnemann School of Medicine, basic plastic
surgery experiences have been integrated into the third-year surgery clerkship as
a requirement for all students, and a Plastic Surgery Pathway has been designed
in conjunction with the school's pathway system for fourth-year students. The
Pathway provides a framework for the student to select a combination of rotations
that will best provide an appropriate broad-based education in preparation for
training in plastic surgery, and it provides extensive guidance by faculty
members in the discipline to assist with career decisions, rotation selection,
and preparations for the residency application process. Students in the Plastic
Surgery Pathway are required to take rotations in medicine, neurology, and
plastic surgery. The remaining rotations are selected from a list of options
based on the student's individual learning needs, interests, and career
aspirations. Early experience with the Plastic Surgery Pathway has shown that it
has been well received by students and faculty, has assisted students with their
career decisions, and has led to an increased student awareness of the importance
and relevance of the specialty.
PMID- 10190456
TI - Coronal incision extending postauricularly.
PMID- 10190457
TI - Tumescent liposuction and median nerve compression.
PMID- 10190458
TI - Treatment of dysesthesias secondary to ultrasonic lipoplasty.
PMID- 10190459
TI - X-chromosome-shaped paired flaps for small and closely located facial defects.
PMID- 10190460
TI - Vermilion border flap.
PMID- 10190461
TI - Commissure-based buccal mucosal flap.
PMID- 10190462
TI - Treatment of cleft palate: more questions than answers.
PMID- 10190463
TI - Bicortical versus monocortical osteosynthesis.
PMID- 10190464
TI - The subperiosteal face lift.
PMID- 10190465
TI - Hypertrophic scars, keloids, and laryngotracheal stenosis.
PMID- 10190466
TI - Keloid after circumcision.
PMID- 10190467
TI - Closure of urethral fistulas with double opposing Z-plasty flaps.
PMID- 10190468
TI - Post breast reduction pain syndrome.
PMID- 10190469
TI - A background material for microvenous anastomosis.
PMID- 10190470
TI - Marjolin's ulcer occurring in hidradenitis suppurativa.
PMID- 10190471
TI - Feminine hygiene sanitary napkins for wound dressings.
PMID- 10190472
TI - Considerations on anesthesia in experiments using rats.
PMID- 10190473
TI - "Dr. Yes, Dr. No, Dr. I'll Say Anything You Want Me To Say".
PMID- 10190474
TI - October of 1998, and still the slides at the convention are unreadable.
PMID- 10190475
TI - The need to improve the quality of our meetings.
PMID- 10190476
TI - Oral-facial-digital syndrome with hypothalamic hamartoma, postaxial ray
hypoplasia of the limbs, and vagino-cystic communication: a new variant?
AB - We report on a 20-month-old girl with hypothalamic hamartoma, left cerebral
atrophy, tongue nodules, oral frenula, micrognathia, hypoplasia of the left ulna,
the fibulae, and right tibia, polysyndactyly of the hands and feet, vagino-cystic
drainage with hydrometrocolpos, megaloureters, and hydronephrosis, agenesis of
urethra, complex partial seizures, and central precocious puberty. The
differential diagnosis is discussed. We conclude that the malformation complex in
this girl is an oral-facial-digital syndrome, but is different from any of the 11
known subtypes.
PMID- 10190477
TI - Microcephaly, colobomatous microphthalmia, short stature, and severe psychomotor
retardation in two male cousins: a new MCA/MR syndrome?
AB - We report on 2 male cousins with minor facial anomalies, microcephaly,
colobomatous microphthalmia, psychomotor retardation, short stature, and skeletal
malformations. The children belong to a highly inbred family. We conclude that
these patients have a previously undescribed autosomal-recessive syndrome.
PMID- 10190478
TI - Metacarpophalangeal pattern profile and bone age in Rett syndrome: further
radiological clues to the diagnosis.
AB - Hand radiographs of 100 girls representing 73% of the known Australian population
of girls with Rett syndrome, age 20 years or less, were available for this study.
Control radiographs were matched for age, sex, and laterality. Bone age was
assessed against standard radiographs in Greulich and Pyle [1959: Radiographic
Atlas of Skeletal Development of the Hands and Wrist, 2nd ed.]. A
metacarpophalangeal pattern (MCPP) profile comparing the relative lengths of the
hand bones with mean population norms by age was produced by converting the
length of each of the 19 metacarpal and phalangeal bones into a Z score. In girls
less than 15 years old, bone age was more advanced in Rett syndrome than in age
matched control girls (left hand P = 0.03, right hand 0.004), but was most
advanced in the younger group and normalized with age. In Rett syndrome, the mean
Z score for the 19 metacarpal and phalangeal bones was 1.0 in children under 5
years, -0.27 in those aged 5-11 years, and -1.7 in those aged 12 years and over.
This variation between age groups was much greater than in the controls. The dips
in the MCPP profile occurred at MC2 and D1, and the peaks at M5, P5, and M4. An
MCPP profile may provide an additional aid to diagnosis in cases of Rett syndrome
where all the criteria are not met, but in children under age 5 years, advanced
bone age may be more helpful as a marker.
PMID- 10190479
TI - Mutchinick syndrome in a Japanese girl.
AB - We report on a 7-year-old Japanese girl with Mutchinick syndrome, a rare
congenital malformation syndrome described in a pair of Argentinean sisters and a
pair of German brothers; both originating from the same geographic region in the
former East Prussia. The girl we describe had most of the clinical manifestations
of the syndrome, including growth and developmental retardation, and craniofacial
anomalies with microcephaly, hypertelorism, a broad straight nose, low-set
malformed ears, and a wide, tented mouth. She also had the following hitherto
undescribed manifestations: ventricular septal defect, palmoplantar
hyperkeratosis, bilateral partial soft-tissue syndactyly of second and third
toes, and megaloureters. The occurrence of the syndrome in a Japanese girl
indicates that the syndrome is not restricted to the descendants of individuals
from a confined region in northeastern Europe.
PMID- 10190480
TI - McCune-Albright syndrome: clinical and molecular evidence of mosaicism in an
unusual giant patient.
AB - Molecular genetics recently uncovered the mystery of the protean picture of
McCune-Albright syndrome by identification of the somatic gain of function
mutations in the GNAS1 gene. Here we present an adult patient with fibrous
dysplasia and an endocrinopathy resulting in unusual giant height. The clinical
diagnosis in the patient could be confirmed by molecular investigations in
tissues involved in the process of fibrous dysplasia.
PMID- 10190482
TI - Congenital malformations in twins: an international study.
AB - Data provided by nine registries based in European and Latin America countries
were analyzed to assess whether there is an excess of malformations in twins
compared to singletons. Specific congenital malformations were coded according to
the ninth revision of the International Classification of Diseases (ICD).
Malformation rates and rate ratios (RR) for twins compared to singletons were
calculated for each registry, and the homogeneity of the RRs was tested using the
test of Breslow and Day. If departure from homogeneity in the different
registries was not significant, registry-adjusted RRs with 95% confidence
intervals were calculated. Overall, among 260,865 twins, 5,572 malformations were
reported. A total of 101 different types of malformations or groups of defects
was identified, and a homogeneous estimate of the RRs among registries was found
for 91.1% of the malformations. Thirty-nine of the 92 malformations with
homogeneous estimates of RRs were more common in twins than in singletons. For
the remaining nine malformations, heterogeneous estimates of RRs were obtained.
This study confirms the majority of already known associations and further
identifies previously unreported malformations associated with twins. In
conclusion, there is an excess of malformations in twins compared with
singletons, and all anatomical sites are involved. The number of specific
malformations associated with twins is higher than that previously reported in
smaller studies.
PMID- 10190481
TI - Acromelic frontonasal dysostosis.
AB - We report on 3 male and 2 female infants with acromelic frontonasal dysostosis.
All 5 had a frontonasal malformation of the face and nasal clefting associated
with striking symmetrical preaxial polysyndactyly of the feet and variable tibial
hypoplasia. In contrast, the upper limbs were normal. This rare variant of
frontonasal dysplasia may represent a distinct autosomal-recessive disorder. We
suggest that the molecular basis of this condition may be a perturbation of the
Sonic Hedgehog (SHH) signalling pathway, which plays an important part in the
development of the midline central nervous system/craniofacial region and the
limbs.
PMID- 10190485
TI - Ascertainment and mutational studies of SRY in nine XY females.
PMID- 10190484
TI - Evidence for a new X-linked mental retardation gene in Xp21-Xp22: clinical and
molecular data in one family.
AB - Linkage analysis was performed in three generations of a French family
segregating a syndromal form of X-linked mental retardation. All affected males
had neonatal hypotonia, seizures, muscular hypodevelopment, and severe mental
deficiency. A peak lod score of 2.90 at a recombination fraction of theta = 0 was
detected for DXS 1052 and DXS 451 (Xp22.13). Recombination between the disease
locus and the polymorphic markers in DXS7163 and DXS1238 suggested a gene mapping
to the Xp22.13-Xp21.2 region. Three candidate genes in this region were
investigated: the cDNA for kinase Rsk-2 involved in Coffin-Lowry syndrome, the
brain-specific exon of a transcript in the DMD locus (DP140 isoform of
dystrophin), and exon 18 of the glycerol kinase gene, which is specific to fetal
brain transcripts. All three sequences were normal.
PMID- 10190483
TI - De novo inverted duplication 9p21pter involving telomeric repeated sequences.
AB - We report on clinical and cytogenetic findings in a boy with partial 9p
duplication, dup(9)(p21pter). Clinical manifestations included facial and hand
anomalies and mental retardation. Fluorescence in situ hybridization (FISH) and
comparative genomic hybridization (CGH) were used to characterize further and
confirm the conventional banding data. Investigation by FISH using whole
chromosome 9 paint probe showed that the additional material was derived from
chromosome 9. Using CGH, a region of gain was found in the chromosome segment
9p21pter. YACs and telomeric probes confirmed the duplicated region. Using the
all-human telomeric sequences probe, intrachromosomal telomeric signal was noted
on the short arm of the abnormal chromosome 9. Mechanism of formation of the
duplication, including intrachromosomal telomeric sequences, is discussed.
PMID- 10190486
TI - Frontal-subcortical hypofunction in the fragile X syndrome.
PMID- 10190487
TI - Decreased proportion of female newborn infants homozygous for the 677 C-->T
mutation in methylenetetrahydrofolate reductase.
PMID- 10190488
TI - Chromosomes participating in translocations typical of malignant hemoblastoses
are also involved in exchange aberrations induced by fast neutrons.
AB - Repeated triple-color fluorescence in situ hybridization was used for the
detection of exchange aberrations among 10 selected chromosomes of human
lymphocytes irradiated with three doses of fast neutrons with a mean energy of 7
MeV. In each hybridization two different pairs of chromosomes were stained.
Defined stage positions of metaphases on a slide were stored on a hard disk and
an automatic scan of images according to these positions was performed after six
successive hybridizations. In this way we obtained six different images of the
same metaphase with differently stained pairs of chromosomes and centromeres. The
comparison of these images enabled the identification of mutual exchanges between
chromosomes 1, 2, 3, 4, 8, 9, 12, 14, 18 and 22. The frequencies of exchanges
were not linearly proportional to the molecular weight of interacting
chromosomes. The most significant were exchanges between chromosomes 14/18, 14/8,
18/8, 8/3, 1/14, 1/8, 3/18, 3/14 and 9/22. The results indicate significant
interactions between chromosomes involved in translocations in B-cell non
Hodgkin's lymphoma and chronic myeloid leukemia. We propose that the reason for
the high frequency of exchanges between these chromosomes is their proximity in
the cell nucleus. It may also be one of the reasons for the induction of specific
translocations leading to malignant transformation of cells.
PMID- 10190489
TI - The effect of functional inactivation of TP53 by HPV-E6 transformation on the
induction of chromosome aberrations by gamma rays in human tumor cells.
AB - The influence of expression of TP53 (formerly known as p53) on the induction of
chromosome aberrations by gamma rays was examined in an isogenic pair of human
tumor cell lines where TP53 expression was normal or inactivated by human
papillomavirus (HPV) type 16 E6 expression. Plateau-phase cultures were exposed
to 0-8 Gy gamma rays and then either immediately released by subculture or held
for 24 h prior to subculture and subsequent cytogenetic analysis. Aberration
frequency was determined only in cells entering their first mitosis after
irradiation, and cells were sampled over a 48-h period to include cells whose
progression into mitosis was delayed. While aberration frequencies were similar
at early harvest times, there was evidence for a subpopulation of more heavily
damaged cells in the E6-transformed cells that cycled into late mitosis. Holding
cells noncycling for 24 h to allow repair of potentially lethal damage eliminated
this subpopulation of more heavily damaged cells. The E6-transformed cells also
had higher levels of chromatid-type aberrations and sister chromatid exchanges,
consistent with an additional defect in kinetics of repair of base damage that is
associated with the E6 transformation. Holding cells noncycling for 24 h
eliminated the elevated levels of chromatid-type aberrations and sister chromatid
exchanges. These studies demonstrate that E6 transformation of human tumor cells
will influence both the frequency and types of chromosome aberrations observed
after radiation exposure, and that these effects are related to the expression of
potentially lethal damage.
PMID- 10190490
TI - Differential antimutagenicity of WR-1065 added after irradiation in L5178Y cell
lines.
AB - The purpose of this study was to determine the antimutagenicity of WR-1065 added
after irradiation of cells of cell lines differing in their ability to rejoin
radiation-induced DNA double-strand breaks (DSBs). The postirradiation
antimutagenicity of WR-1065 at the thymidine kinase locus was demonstrated for
L5178Y (LY)-S1 cells that are deficient in repair of DNA DSBs. Less
postirradiation antimutagenicity of WR-1065 was observed in LY-R16 and LY-SR1
cells, which are relatively efficient in DSB repair. Postirradiation treatment
with WR-1065 had only a small stimulatory effect on DSB rejoining. A 3-h
incubation of irradiated LY cells with WR-1065 caused slight changes in the
distribution of cells in the phases of the cell cycle that differed between LY-S1
and LY-SR1 cells. Both LY-S1 and LY-SR1 cells were protected against the
cytotoxic and mutagenic effects of radiation when WR-1065 was present 30 min
before and during the irradiation. We conclude that the differential
postirradiation effects of WR-1065 in the LY-S1 and LY-SR1 cells are not caused
by differences in cellular uptake of the radioprotector or in its radical
scavenging activity. Possible mechanisms for the postirradiation antimutagenicity
of WR-1065 are discussed.
PMID- 10190491
TI - Rejoining of DNA double-strand breaks in Ku80-deficient mouse fibroblasts.
AB - The role of Ku80 in the repair of DNA double-strand breaks (DSBs) was examined in
fibroblasts derived from a Ku80 knockout mouse model described by Nussenzweig et
al. (Nature 382, 551-555, 1996). Primary fibroblasts from Ku80+/+ and Ku80-/-
mice were immortalized by transfection with plasmids containing either the human
MYC proto-oncogene or the Simian virus 40 (SV40) T antigen and were used to
measure induction and rejoining of DSBs after exposure to ionizing radiation. The
number of DSBs in the cells was quantified by either asymmetric field-inversion
gel electrophoresis (AFIGE) or clamped homogeneous electrical-field gel
electrophoresis (CHEF). The latter method was introduced for a more reliable
quantification of repair even when DNA degradation occurs in a fraction of the
irradiated cell population during the postirradiation incubation time. The
results confirm that Ku80-deficient mouse fibroblasts are sensitive to ionizing
radiation and demonstrate that the increased radiosensitivity may result from a
deficiency in DSB rejoining. The results further indicate that unless techniques
are employed that allow for distinction between DNA degradation and DNA repair,
erroneous conclusions may be drawn regarding the potential of cells to repair
DSBs.
PMID- 10190492
TI - Radiation-induced recombination is dependent on Ku80.
AB - We have recently shown that irradiating cells prior to transfection induces
recombination, as manifested by increased stable transduction of both plasmid and
adenoviral vectors. We hypothesized that Ku proteins, which have previously been
shown to be involved in both recombination and the repair of DNA damage after
irradiation, would likely be important mediators of radiation-induced
recombination. The present work demonstrates that Ku80 is essential for radiation
induced recombination. While human and hamster Ku80 are equally effective at
restoring the transfection efficiency and radiation resistance of xrs-5 cells,
human Ku80 is much more effective at radiation-induced recombination than hamster
Ku80. This difference is not due to differences in Ku80 expression or DNA end
binding activity, but it may be due to structural differences between human and
hamster Ku80.
PMID- 10190493
TI - Protein-DNA complexes containing DNA-dependent protein kinase in crude extracts
from human and rodent cells.
AB - The DNA-dependent protein kinase (DNA-PK) is composed of a large catalytic
subunit (DNA-PKcs) and a DNA-binding protein, Ku. Cells lacking DNA-PK activity
are radiosensitive and are defective in DNA double-strand break repair and V(D)J
recombination. Although much information regarding the interactions of Ku with
DNA ends is available, relatively little is known about the interaction of DNA
PKcs with DNA-bound Ku. Here we show, using electrophoretic mobility shift
assays, that chemical crosslinkers enhance the formation of protein-DNA complexes
containing DNA-PKcs, Ku and other proteins in extracts from cells of normal human
cell lines. Extracts from cells of the radiosensitive human cell line M059J,
which lacks DNA-PKcs, are not competent to form these protein-DNA complexes,
while addition of purified DNA-PKcs protein restores complex formation. This
assay may be useful for screening for DNA-PK function in cells of human cell
lines and for identifying proteins that interact with the DNA-PK-DNA complex. We
also show that Ku protein in rodent cells can interact with human DNA-PKcs;
however, this assay may be less useful for studying Ku/DNA-PKcs interactions in
cells of rodent cell lines due to the low abundance of DNA-PKcs in these cells.
PMID- 10190494
TI - Rejoining kinetics of DNA single- and double-strand breaks in normal and DNA
ligase-deficient cells after exposure to ultraviolet C and gamma radiation: an
evaluation of ligating activities involved in different DNA repair processes.
AB - The repair kinetics for rejoining of DNA single- and double-strand breaks after
exposure to UVC or gamma radiation was measured in cells with deficiencies in DNA
ligase activities and in their normal counterparts. Human 46BR cells were
deficient in DNA ligase I. Hamster EM9 and EM-C11 cells were deficient in DNA
ligase III activity as a consequence of mutations in the XRCC1 gene. Hamster XR-1
cells had mutation in the XRCC4 gene, whose product stimulates DNA ligase IV
activity. DNA single- and double-strand breaks were assessed by the comet assay
in alkaline conditions and by the technique of graded-field gel electrophoresis
in neutral conditions, respectively. 46BR cells, which are known to re-ligate at
a reduced rate the DNA single-strand breaks incurred during processing of damage
induced by UVC but not gamma radiation, were shown to have a normal repair of
radiation-induced DNA double-strand breaks. EM9 cells exhibited a reduced rate of
rejoining of DNA single-strand breaks after exposure to ionizing radiation, as
reported previously, as well as UVC radiation. EM-C11 cells were deficient in the
repair of radiation-induced-DNA single-strand breaks but, in contrast to EM9
cells, demonstrated the same kinetics as the parental cell line in the resealing
of DNA breaks resulting from exposure to UVC radiation. Both EM9 and EM-C11 cells
displayed a significant defect in rejoining of radiation-induced-DNA double
strand breaks. XR-1 cells were confirmed to be highly deficient in the repair of
radiation-induced DNA double-strand breaks but appeared to rejoin DNA single
strand breaks after UVC and gamma irradiation at rates close to normal. Taken
together these results indicate that: (1) DNA ligase I is involved only in
nucleotide excision repair; (2) DNA ligase IV plays an important role only in
repair of DNA double-strand breaks; and (3) DNA ligase III is implicated in base
excision repair and in repair of DNA double-strand breaks, but probably not in
nucleotide excision repair.
PMID- 10190495
TI - Condensed chromatin and cell inactivation by single-hit kinetics.
AB - Mammalian cells are extremely sensitive to gamma rays at mitosis, the time at
which their chromatin is maximally condensed. The radiation-induced killing of
mitotic cells is well described by single-hit inactivation kinetics. To
investigate if radiation hypersensitivity by single-hit inactivation correlated
with chromatin condensation, Chinese hamster ovary (CHO) K1 (wild-type) and xrs-5
(radiosensitive mutant) cells were synchronized by mitotic shake-off procedures
and the densities of their chromatin cross sections and their radiosensitivities
were measured immediately and 2 h into G1 phase. The chromatin of G1-phase CHO K1
cells was dispersed uniformly throughout their nuclei, and its average density
was at least three times less than in the chromosomes of mitotic CHO K1 cells.
The alpha-inactivation co-efficient of mitotic CHO K1 cells was approximately 2.0
Gy(-1) and decreased approximately 10-fold when cells entered G1 phase. The
density of chromatin in CHO xrs-5 cell chromosomes at mitosis was greater than in
CHO K1 cell chromosomes, and the radiosensitivity of mitotic CHO xrs-5 cells was
the greatest with alpha = 5.1 Gy(-1). In G1 phase, CHO xrs-5 cells were slightly
more resistant to radiation than when in mitosis, but a significant proportion of
their chromatin was found to remain in condensed form adjacent to the nuclear
membrane. These studies indicate that in addition to their known defects in DNA
repair and V(D)J recombination, CHO xrs-5 cells may also be defective in some
process associated with the condensation and/or dispersion of chromatin at
mitosis. Their radiation hypersensitivity could result, in part, from their DNA
remaining in compacted form during interphase. The condensation status of DNA in
other mammalian cells could define their intrinsic radiosensitivity by single-hit
inactivation, the mechanism of cell killing which dominates at the dose fraction
size (1.8-2.0 Gy) most commonly used in radiotherapy.
PMID- 10190496
TI - Quantitative assessment of the contribution of clustered damage to DNA double
strand breaks induced by 60Co gamma rays and fission neutrons.
AB - The induction of DNA strand breaks by fission neutrons was studied in aqueous
plasmid (pBR322) DNA under aerobic conditions for a wide range of hydroxyl
radical (*OH) scavenger concentrations and was compared to the induction of
strand breaks by 6OCo gamma rays. Strand breaks were measured using agarose gel
electrophoresis coupled with sensitive 32P-based phosphor imaging. Yields are
reported for DNA single-strand breaks (SSBs) and double-strand breaks formed
linearly with dose (alphaDSBs). The fraction of alphaDSBs that were dependent on
the multiply damaged site (MDS) or clustered damage mechanism was also calculated
using a model. G values for SSBs and alphaDSBs declined with increasing *OH
scavenging capacity. However, with increasing *OH scavenging capacities, the
decrease in yields of strand breaks for fission neutrons was not as pronounced as
for gamma rays. The percentage of alphaDSBs for gamma rays was dependent on *OH
scavenging capacity, appearing negligible at low scavenging capacities but
increasing at higher scavenging capacities. In contrast, fission neutrons induced
high percentages of alphaDSBs that were approximately independent of *OH
scavenging capacity. The levels of alphaDSBs formed by the MDS mechanism after
exposure to fission neutrons are consistent with the expected distinctive
features of high-LET energy deposition events and track structure. The results
also confirm observations made by others that even for low-LET radiation, the MDS
mechanism contributes significantly to DNA damage at cell-like scavenging
conditions.
PMID- 10190497
TI - Pulsed-dose-rate and low-dose-rate brachytherapy: comparison of sparing effects
in cells of a radiosensitive and a radioresistant cell line.
AB - Pulsed-dose-rate regimens are an attractive alternative to continuous low-dose
rate brachytherapy. However, apart from data obtained from modeling, only a few
in vitro results are available for comparing the biological effectiveness of both
modalities. Cells of two human cell lines with survival fractions of 80% (RT112)
and 10% (HX142) after a single dose of 2 Gy and with different halftimes for
split-dose recovery and low-dose recovery were used. The cells were irradiated
with a continuous low dose rate (80 cGy per hour) or with pulsed dose rate. Two
different pulsed dose rates were tested: 4.25 Gy/h and 63 Gy/h. The effects of
dose per pulse and the length of the interval between the pulses were
investigated while keeping the overall treatment time constant. Survival after
low-dose-rate irradiation was indistinguishable from that after pulses of 4.25
Gy/h in cells of both cell lines. Survival decreased with increasing dose per
pulse. When the dose rate during the pulses was increased, survival decreased
even further. This effect was most pronounced for the radiosensitive HX142 cells.
In clinical pulsed-dose-rate brachytherapy, iridium sources move stepwise through
the implant and deliver pulses at a high dose rate locally. These high-dose-rate
pulses produce greater biological effectiveness compared to continuous low dose
rate; this should be taken into account.
PMID- 10190498
TI - Investigation of microvessel density after irradiation.
AB - It is believed that malignant cell populations need the development of
microvessels to grow and metastasize. The aim of our investigation was to find
out whether gamma irradiation can affect proliferation of endothelial cells and
thus can affect microvessel density in vivo. We used fertilized chicken eggs. The
vascularized part of the yolk sac membrane (area vasculosa) of the eggs received
single doses of 2 to 10 Gy. Forty-eight hours after irradiation, the area
vasculosa was photographed in vivo, and prints of known magnification were
evaluated to determine the density of the blood vessels. Microvessel count is the
well-established marker used to determine vascular density. In addition, the
proliferative activity of endothelial cells in the yolk sac membrane was
determined by estimating the expression of proliferating cell nuclear antigen
(PCNA). PCNA immunostaining was assessed immunohistochemically. After a single
dose of 10 Gy, a statistically significant increase in vascular density was found
compared to values determined at 0, 2, 4 and 8 Gy (P < 0.05). Twenty-four hours
after 10 Gy irradiation, 44.8% (mean) of the endothelial cells were PCNA
positive. This was significantly higher (P < 0.05) compared to the results 24 h
after 4.0 Gy (22.7%) and compared to control (19.4%). Twenty-four hours later,
i.e. 48 h after irradiation with 10 Gy, the endothelial cells also showed a
significantly (P < 0.05) higher PCNA positivity with a mean of 34.1% compared to
the nonirradiated area vasculosa (18.1%) and compared to the results after 4.0 Gy
irradiation (12.0%). The prerequisite for blood vessel formation is the
proliferation of endothelial cells. Thus a single-dose irradiation with 10 Gy
induces endothelial cell proliferation and subsequent neovascularization in the
area vasculosa of the fertilized egg.
PMID- 10190499
TI - Radiation-induced impairment of urinary bladder function in mice: fine structure
of the acute response and consequences on late effects.
AB - The time course and dose response of radiation-induced impairment of urinary
bladder function in the mouse were assessed after local irradiation with graded
single doses. Bladder capacity was defined by transurethral cystometry; a
reduction in bladder volume at an intravesical pressure of 10 mmHg by > or =50%
of the individual pretreatment control value was considered a positive radiation
reaction. Reversible effects of radiation on the urinary bladder were found
during the first 30 days postirradiation, followed by a symptom-free latent
period and irreversible late changes. Maximum-likelihood analysis revealed that
the acute response is composed of two distinct waves from days 1-15 and days 16
30, with mean latent times of 7.1 days [95% confidence interval (5.4, 9.0)] and
23.3 days (21.9, 24.5), respectively, which describe the data significantly
better than a single normal distribution (P = 0.0052). The ED50 values (+/- their
standard deviation sigma), i.e. the doses at which 50% of the irradiated animals
show the > or = 50% reduction in bladder capacity during each of the two
intervals, were 21.7 +/- 4.1 and 19.3 +/- 3.9 Gy for the first and the second
acute wave, respectively. The ED50 for the late functional effects was 18.7 +/-
2.4 Gy. Multivariate analysis demonstrated (1) that a response during the first
acute wave correlated significantly with a reaction in the second acute wave (P =
0.0066), and (2) that a response during the second but not the first acute wave
correlated significantly with the development of a late response (P = 0.0008). In
conclusion, the present analysis suggests that the radiation response of the
urinary bladder of the mouse displays a significant consequential component.
However, further studies are required to demonstrate if the frequency of late
sequelae can be decreased by an early intervention in the sequence of pathogenic
processes.
PMID- 10190500
TI - Modified absorptive and secretory processes in the rat distal colon after neutron
irradiation: in vivo and in vitro studies.
AB - Impaired fluid and electrolyte transport in the intestine is a well-recognized
characteristic of radiation-induced pathologies in the gastrointestinal tract.
The aim of this study was to investigate the responsiveness of the epithelium of
the colon of the rat to electrical and pharmacological (serotonin, carbachol)
stimulation concomitantly with in vivo assessment of the absorptive capacity of
the colon at 1, 3, 5 and 7 days after 3.8 Gy whole-body exposure to neutrons. The
responsiveness of rat colon in vitro to electrical stimulation and the number of
mast cells were measured to examine the role of neuroimmune networks in radiation
induced dysfunction. Animals showed an impaired capacity of the colon to absorb
water and sodium from 3 to 5 days after irradiation together with decreased
responsiveness to electrical and pharmacological stimulation. The time course of
decreased responsiveness to neural stimulation was similar to that of impaired
absorption observed in vivo, but it was not correlated with variations in mast
cell numbers. Histological (mast cells) and biochemical analyses (myeloperoxidase
and NO synthase activities) did not find evidence of a marked infiltration and/or
activation of inflammatory cells. Thus the impaired absorptive capacity of the
colon observed after irradiation occurs concomitantly with decreased neural
influence, and is possibly related to reduced epithelial functional capacity but
not to decreased mast cell numbers.
PMID- 10190501
TI - Preoperative treatment of rectal cancer with radiation, chemotherapy and
hyperthermia: analysis of treatment efficacy and heat-shock response.
AB - Preoperative treatment of locally advanced rectal cancer with radiation,
chemotherapy and hyperthermia is analyzed with regard to heat-shock response. In
23 patients with locally advanced rectal cancer (uT3/uT4), hyperthermia was
administered in combination with radiotherapy and chemotherapy. In parallel, the
effect of the treatment on levels of the heat-shock proteins HSP27 and inducible
HSP70 in tumors and surrounding tissues was investigated by Western blotting. The
patients' sera were also examined for autoantibodies against HSPs. HSP27 and
inducible HSP70 were detected in most rectal tumors and surrounding tissues
before and after treatment. HSP27 and inducible HSP70 levels had changed in 10
tumors after treatment. However, prior to treatment, there existed an unexpected
diversity in HSP levels in the tumors and surrounding tissue. Hyperthermia doses
in cumulative minutes for which 90% of the tumor is above the reference
temperature (cum min T90 > or = 15 min) led to increased survival and response
compared to that of a control group of patients treated without or with low-dose
hyperthermia (cum min T90 < 15 min). However, there was no correlation to
different expression of the HSPs. Hyperthermia as used in this setting does not
lead to any sustained expression of HSPs in either the tumor or the surrounding
tissue.
PMID- 10190502
TI - Increase in radiation-induced HPRT gene mutation frequency after nonthermal
exposure to nonionizing 60 Hz electromagnetic fields.
AB - It is widely accepted that moderate levels of nonionizing electric or magnetic
fields, for example 50/60 Hz magnetic fields of about 1 mT, are not mutagenic.
However, it is not known whether such fields can enhance the action of known
mutagens. To explore this question, a stringent experimental protocol, which
included blinding and systematic negative controls, was implemented, minimizing
the possibility of observer bias or experimental artifacts. As a model system, we
chose to measure mutation frequencies induced by 2 Gy gamma rays in the redox
sensitive hypoxanthine-guanine phosphoribosyl transferase (HPRT) gene in Chinese
hamster ovary cells. We tested whether a 12-h exposure to a 60 Hz sinusoidally
oscillating magnetic-flux density (Brms = 0.7 mT) could affect the mutagenic
effects of ionizing radiation on the HPRT gene locus. We determined that the
magnetic-field exposure induced an approximate 1.8-fold increase in HPRT mutation
frequency. Additional experiments at Brms = 0.23 and 0.47 mT revealed that the
effect was reduced at lower flux densities. The field exposure did not enhance
radiation-induced cytotoxicity or mutation frequencies in cells not exposed to
ionizing radiation. These results suggest that moderate-strength, oscillating
magnetic fields may act as an enhancer of mutagenesis in mammalian cells.
PMID- 10190503
TI - Restoration of mutant TP53 to normal TP53 function by glycerol as a chemical
chaperone.
AB - We have previously reported that heat stress induces expression of wild-type TP53
(formerly known as p53) activated factor 1 (CDKN1A, formerly known as WAF1) only
when TP53 protein is wild-type using cells of a human glioblastoma cell line (A
172) and cells of its transformant (A-172/mp53/ 143) with a mutant TP53 (point
mutation at codon 143 from Val to Ala) vector. Transfection of A-172 cells with
the mutant TP53 vector abolished the heat-induced expression of CDKN1A,
demonstrating the dominant negative nature of this TP53 mutant over the
endogenous wild-type TP53. This kind of dominant negative TP53 mutant occurs
frequently in various types of cancer. Overcoming this dominance or restoring the
normal functions to these TP53 mutants is a new strategy for TP53-targeted cancer
therapies. We examined whether glycerol can act as a chemical chaperone to
correct the mutant TP53 conformation. No CDKN1A expression was induced after
heating or treatment with glycerol at concentrations of 0.6 and 1.2 M in these
transformants. In contrast, A-172/mp53/ 143 cells showed CDKN1A expression when
they were heated in the presence of glycerol at 0.6 or 1.2 M, which was similar
to the response of the parental and neo vector-transfected control cells. To test
the generality of the effects of glycerol on mutant TP53, we used human
osteosarcoma Saos-2 cells (lacking TP53) transfected with mutant TP53 and cells
of two other human glioblastoma cell lines carrying mutant TP53. These cells
showed similar CDKN1A expression when heated in the presence of glycerol at 0.6
or 1.2 M. These results suggest that glycerol is effective in restoring several
TP53 mutants to normal TP53 function, leading to normal CDKN1A expression after
heat stress. This observation provides a novel tool for correction of mutant TP53
conformation and may be applicable for TP53-targeted cancer therapy.
PMID- 10190504
TI - Comments on "Enhanced neoplastic transformation in an inhomogeneous radiation
field: an effect of exposure to supralethally damaged cells" by Crompton et al.
(Radiat. Res. 149, 651-653, 1998)
PMID- 10190505
TI - Enhanced transformation: of mice, men and inhomogeneous radiation fields.
PMID- 10190506
TI - Cell communication and the "bystander effect".
PMID- 10190507
TI - Efficacy of invasive strategy for the management of acute myocardial infarction
complicated by cardiogenic shock.
AB - This retrospective study evaluates the influence of an invasive strategy of
urgent coronary revascularization on the in-hospital mortality of patients with
acute myocardial infarction (AMI) complicated early by cardiogenic shock. Among
1,981 patients with AMI admitted to our institution from 1994 to 1997, 162
patients (8.2%) developed cardiogenic shock unrelated to mechanical
complications. The strategy of management was considered invasive if an urgent
coronary angiography was indicated within 24 hours of symptom onset. Every other
strategy was considered conservative. Fifty-seven patients who developed the
shock late or after a revascularization procedure, or who died on admission, were
excluded. The strategy was invasive in 73 patients (70%). Five of them died
before angiography could be performed and 65 underwent angioplasty (success rate
72%). By univariate analysis the invasive strategy was associated with a lower
mortality than conservative strategy (71% vs 91%, p = 0.03), but this association
disappeared after adjustment for baseline characteristics. Older age, nonsmoking,
and previous ischemic heart disease were independent predictors of mortality. In
conclusion, we have failed to demonstrate that a strategy of urgent coronary
revascularization within 24 hours of symptom onset for patients with AMI
complicated by cardiogenic shock is independently associated with a lower in
hospital mortality. This strategy was limited by the high mortality within 1 hour
of admission in patients with cardiogenic shock, the modest success rate of
angioplasty in this setting, and the powerful influence of some adverse baseline
characteristics on prognosis.
PMID- 10190508
TI - Thrombectomy with AngioJet catheter in native coronary arteries for patients with
acute or recent myocardial infarction.
AB - The AngioJet thrombectomy catheter removes thrombi by rheolytic fragmentation and
suction. The purpose of this study was to identify the efficacy and safety of
this new device. Myocardial infarction (MI) is associated with intracoronary
thrombus. Intracoronary thrombus has been identified as a risk factor of
unfavorable outcome after percutaneous transluminal coronary angioplasty. To what
extent the AngioJet is applicable or effective for acute or recent MI in native
coronary artery is not clear. Thrombectomy with the AngioJet was attempted in 31
patients with 31 native coronary arteries selected from 304 patients with acute
or recent MI. Follow-up angiography was performed at 3 to 6 months. Procedure
success was achieved in 29 patients (94%). Adjunctive balloon angioplasty was
performed after AngioJet thrombectomy in 30 patients (97%), and in only 1 patient
(3%) AngioJet thrombectomy was the sole procedure. Subsequent stenting after
balloon angioplasty was attempted successfully in 12 patients (40%) without
thrombotic complications. Thrombolysis In Myocardial Infarction trial flow
grading increased from 0.70 +/- 0.97 before to 2.61 +/- 0.88 after AngioJet
thrombectomy (p <0.0001), to 2.84 +/- 0.64 after adjunctive procedures (p =
0.070). At follow-up angiography restenosis rate was 21% but Thrombolysis In
Myocardial Infarction flow 3 was present in all patients. The restenosis rate of
stented patients was 8%. There were no major events during in-hospital and follow
up. The AngioJet can be used safely and successfully to remove thrombus from the
native coronary artery of patients with MI. Thrombus removal makes subsequent
stenting safe and uncomplicated. The restenosis rate was considered to be
acceptable.
PMID- 10190509
TI - Heart rate variability and occurrence of ventricular arrhythmias during balloon
occlusion of a major coronary artery.
AB - Experimental studies suggest that autonomic mechanisms are important in the
genesis of ischemia-induced malignant ventricular arrhythmias, but the role of
the autonomic nervous system in human arrhythmogenesis is not well known. To
assess whether heart rate variability (HRV) predicts the occurrence of
ventricular arrhythmias during acute coronary artery occlusion, we performed
continuous electrocardiographic, heart rate, and blood pressure recordings before
and during a 2-minute balloon occlusion of a stenotic coronary artery in 252
patients with no baseline ventricular premature complexes (VPCs). The ranges of
nonspecific responses in heart rate and blood pressure were determined by
analyzing a control group of 19 patients with no ischemia during a 2-minute
balloon inflation in a totally occluded coronary artery. Balloon occlusion of a
coronary artery was stopped because of complex, i.e., bigeminal or repetitive,
VPCs in 14 patients, and solitary (<5) VPCs were observed in an additional 19
patients. During coronary occlusion, HRV increased (p <0.001) and heart rate
decreased (p <0.05) in patients with no VPCs, whereas an opposite tendency to
reduction in HRV (p = 0.08) was observed in patients with complex VPCs. Complex
VPCs were observed in 5 (42%) of the 12 patients with a significant coronary
occlusion-induced decrease in HRV, in 7 (3.5%) of 200 patients with no change in
HRV, but in none of the 40 patients with a significant increase in HRV (p
<0.001). Baseline HRV did not predict the occurrence of VPCs during coronary
occlusion. Logistic regression analysis identified the decrease in HRV (p <0.001)
to be the only independent predictor of complex VPCs. In conclusion, coronary
occlusion-induced increase in HRV seems to protect against occurrence of complex
ventricular arrhythmias during the early phase of abrupt coronary occlusion,
suggesting that vagal activation may modify the outcome of acute coronary events
in patients with coronary artery disease.
PMID- 10190510
TI - Timing of coronary stent thrombosis in patients treated with ticlopidine and
aspirin.
AB - In patients receiving coronary stents treated with aspirin and coumadin, the peak
incidence of stent thrombosis occurs on the fifth and sixth days following the
implantation procedure. Little is known about the timing of stent thrombosis in
patients treated with aspirin and ticlopidine. We compared the timing of coronary
stent thrombosis in patients treated with ticlopidine and aspirin with the timing
in those receiving coumadin and aspirin. A retrospective databank analysis was
performed and 39 patients were identified who experienced stent thrombosis after
successful coronary stent implantation. Of these, 21 had been treated with
ticlopidine and aspirin and 18 with coumadin and aspirin therapy. The median time
from stent implantation to stent thrombosis in the ticlopidine and aspirin group
was 12 hours (interquartile range 6 to 72 hours) compared with 4 days in the
coumadin and aspirin group (interquartile range 21 to 68 hours) (p <0.0001).
There was no significant difference between the timing of stent thrombosis in
patients treated with abciximab in addition to ticlopidine and aspirin (median 17
hours, interquartile range 6 to 29) versus ticlopidine and aspirin patients who
did not receive abciximab (median 11 hours, interquartile range 9 to 12, p =
0.57). Thus, in patients who receive coronary stents, stent thrombosis occurs
much earlier after the procedure in patients treated with ticlopidine and aspirin
than in patients treated with anticoagulation therapy.
PMID- 10190511
TI - Does the specific intravascular ultrasound criterion used to optimize stent
expansion have an impact on the probability of stent restenosis?
AB - Intravascular ultrasound (IVUS) imaging has been used to optimize stent
implantation in coronary arteries, but the criteria used were chosen on an
empiric basis. The aim of this study was to determine whether any of these
criteria have an independent role in predicting the probability of freedom from
restenosis. The study population consisted of 425 patients (496 lesions) who
underwent angiographically successful IVUS-guided stenting. Five IVUS criteria
were studied: (1) intrastent minimal lumen cross-sectional area (ISMLCSA) > or =9
mm2; (2) ISMLCSA (> or =9 mm2 and > or =80% of average reference lumen cross
sectional area [CSA]); (3) ISMLCSA > or =90% of average reference lumen CSA; (4)
ISMLCSA > or =90% of distal reference lumen CSA; and (5) ISMLCSA > or =55% of
average reference vessel CSA. These criteria were met in 33%, 29%, 68%, 82%, and
69% of lesions, respectively. Angiographic follow-up was performed in 335 of 421
eligible patients (80%) at 5.3 +/- 2.7 months. An absolute ISMLCSA > or =9 mm2
was associated with the lowest restenosis, but this criterion was primarily
achieved in large vessels. The only criterion that was associated with higher
probability of freedom from restenosis independently from vessel size was an
ISMLCSA > or =55% of average reference vessel CSA. Therefore, when IVUS is used
to guide stent implantation an effort should be made to achieve the largest lumen
safely possible. An ISMLCSA > or =55% of the average reference vessel CSA seems
to be the most appropriate criterion in terms of frequency of achievement and in
terms of increasing the probability of freedom from restenosis.
PMID- 10190512
TI - Angiographic and clinical outcomes following acute infarct angioplasty on
saphenous vein grafts.
AB - Acute infarct angioplasty on aortocoronary saphenous vein grafts (SVGs) poses
significant challenges because of their degenerate morphology and presence of
significant thrombus. Of 370 acute, primary, or rescue myocardial infarct
angioplasties performed over 3 years, 21 (5.7%) were on SVGs in patients who had
undergone previous coronary artery bypass grafting a mean of 7.2 years earlier.
Mean duration of chest pain to start of intervention was 3.9 +/- 3.2 hours; 6
(29%) patients presented with cardiac shock and 4 had failed treatment with
thrombolytic drugs. At intervention, 11 (52%) of the culprit SVGs were totally
occluded. Flow was reestablished or improved in 18 (86%), but classified as
Thrombolysis In Myocardial Infarction trial grade 3 in only 10 patients (48%).
Distal embolization and "no reflow" occurred with a frequency of 57% and 71%,
respectively. In-hospital mortality was 19%. At 6 months, freedom from death,
repeat target vessel revascularization, or recurrent myocardial infarction was
55%. In 349 patients undergoing native vessel intervention, success and
Thrombolysis In Myocardial Infarction trial 3 flow rates were seen in 95% and 73%
of patients, respectively, and in-hospital mortality was 7.9%. This present study
demonstrates that infarct angioplasty on culprit SVGs can be successful but is
associated with higher rates of embolic complications and worse acute and long
term clinical outcomes compared with a parallel experience of acute infarct
angioplasty on native coronary arteries.
PMID- 10190513
TI - Comparison of measurement of left ventricular ejection fraction by Tc-99m
sestamibi first-pass angiography with electron beam computed tomography in
patients with anterior wall acute myocardial infarction.
AB - The goal of this study was to compare measurements of left ventricular (LV)
ejection fraction (EF) by first-pass radionuclide angiography ("first-pass
angiography") using technetium-99m (Tc-99m) sestamibi with those by contrast
enhanced electron beam computed tomography ("electron beam tomography") as a
reference technique in patients with an anterior wall acute myocardial infarction
(AMI). Twenty-five patients with first Q-wave anterior wall AMI underwent paired
electron beam tomographic and first-pass angiographic studies (mean, 1 day
apart). Fourteen patients had 2 sets of measurements of the LVEF obtained by both
methods (separated by at least 6 weeks), for a total of 39 paired measurements.
LVEF by electron beam tomography was calculated from absolute systolic and
diastolic LV chamber volumes. LV volumes by electron beam tomography were 199 +/-
51 ml at end-diastole and 111 +/- 42 ml at end-systole. Mean LVEF was 45 +/- 11%
by first-pass tomography and 46 +/- 9% by electron beam tomography. The linear
correlation coefficient between both methods was 0.82 (p <0.0001), with slope =
1.0, y-intercept = -1.1, and SEE = 6.1. The mean difference between the 2 methods
was -0.7 +/- 6.0 EF units (p = 0.75). The correlation between the differences and
means of both methods was 0.34 (p = 0.04), indicating a trend for first-pass
angiography to overestimate LVEF in the higher range. LVEFs measured by first
pass angiography in patients with abnormal LV geometry and contraction patterns
caused by anterior wall AMI agree well with those measured by electron beam
tomography in the clinically relevant range.
PMID- 10190514
TI - Noninvasive assessment of hemodynamic subsets in patients with acute myocardial
infarction using digital color Doppler velocity profile integration and pulmonary
venous flow analysis.
AB - Four major hemodynamic subsets from cardiac index (CI) and mean pulmonary artery
(PA) wedge pressure with a PA catheter usually reflect clinical status and
prognosis of patients with acute myocardial infarction (AMI). Recently, a new
color Doppler technique has been developed for automated cardiac output
measurements (ACOM). Color Doppler echocardiography also provides noninvasive
estimation of PA wedge pressure from pulmonary venous (PV) flow analysis. This
study evaluates the value of ACOM and PV flow analysis by color Doppler
echocardiography for the assessment of hemodynamic subsets in patients with AMI.
We performed ACOM and PV flow analysis by color Doppler echocardiography in 55
patients with AMI who underwent hemodynamic assessment with a PA catheter. From
both noninvasive and invasive methods, we classified hemodynamic subsets as
follows: subset I: normal hemodynamics (CI >2.2 L/min/m2, PA wedge pressure < or
=18 mm Hg); subset II: pulmonary congestion (CI >2.2 L/min/m2, PA wedge pressure
>18 mm Hg); subset III: peripheral hypoperfusion (CI < or =2.2 L/min/m2, PA wedge
pressure < or =18 mm Hg); and subset IV: pulmonary congestion and peripheral
hypoperfusion (CI < or =2.2 L/min/m2, PA wedge pressure >18 mm Hg). Doppler
assessment of hemodynamic subsets was possible in 50 of 55 patients (91%). CI
from ACOM correlated well with that from the thermodilution method (r = 0.94)
with close agreement. There was a good correlation between the systolic fraction
(systolic velocity-time integral expressed as a fraction of the sum of systolic
and diastolic velocity-time integrals) of PV flow and PA wedge pressure measured
from cardiac catheterization (r = -0.83). When we determined the value of 45% in
the systolic fraction as the cut-off point in predicting >18 mm Hg in PA wedge
pressure, there was 90% (45 of 50 patients) agreement between noninvasive and
invasive hemodynamic subsets. Thus, ACOM and PV flow analysis by color Doppler
echocardiography is useful in the noninvasive assessment of hemodynamic subsets
in patients with AMI.
PMID- 10190515
TI - Lessons learned from a community hospital chest pain center.
AB - The iterative lessons from our studies suggest that creation of a chest pain
center alone will not change the practice of chest pain management by most
physicians. In 1993 we established a chest pain center; in mid-1995 we
established a patient management algorithm directing intermediate-risk patients
to the chest pain center rather than admit them to the hospital. The creation of
a chest pain center did not reduce the rate of chest pain admission by mid-1995.
After the patient management algorithm was created, admittances dropped by a rate
of 21% (p <0.001) and chest pain center usage increased by +1,726% (p <0.001).
Among the 473 patients treated and discharged in the chest pain center after mid
1995, 333 (70%) were considered intermediate risk. No patient died after
discharge from the chest pain center and there was 1 non-Q-wave myocardial
infarction. We conclude that a chest pain management algorithm in a chest pain
center can be safe, yet effective, for identifying high-risk patients for
admission and low-risk patients for discharge.
PMID- 10190516
TI - Long-term prognostic value of preoperative dipyridamole thallium imaging and
clinical indexes in patients with diabetes mellitus undergoing peripheral
vascular surgery.
AB - The objective of this study is to assess the prognostic impact of preoperative
dipyridamole thallium imaging and clinical variables on the long-term outcome of
diabetic patients undergoing peripheral vascular surgery. Complete follow-up was
obtained in 101 consecutive patients with diabetes mellitus undergoing routine
dipyridamole thallium scintigraphy before vascular surgery (mean 4.2 +/- 3.2
years, range 1 month to 11 years). Low risk was defined by diabetes alone with a
normal resting electrocardiogram. High risk was defined as a history of angina,
myocardial infarction, congestive heart failure, or resting electrocardiogram
abnormalities. There were 71 deaths in 98 patients discharged alive from the
hospital (median survival 4.4 years). Age, the presence of resting
electrocardiogram abnormalities, and an abnormal thallium scan were independent
predictors of late death. After adjusting for age >70 years and thallium
abnormalities, high-risk patients had a death rate 4.8 times (95% confidence
interval 1.7 to 13.4, p <0.002) greater than low-risk patients. The presence of
>2 reversible thallium defects was useful in further risk stratification of both
low- and high-risk patients. Low-risk patients with >2 reversible defects had a
median survival of 4.0 years compared with 9.4 years in those with < or =2
reversible defects (p <0.001). Similarly, high-risk patients with < or =2
reversible defects had an intermediate median survival rate of 4.7 years compared
with 1.8 years in the group with >2 reversible defects (p <0.001). Therefore,
advanced age and the presence of resting electrocardiographic or thallium
abnormalities identifies a subset of diabetic patients with a poor long-term
outcome after vascular surgery. Combined clinical and thallium variables may
identify a population in whom intensive medical or surgical interventions may be
warranted to reduce both perioperative and late cardiac events.
PMID- 10190517
TI - Efficacy and safety of simvastatin for high-risk hypercholesterolemia.
AB - Ten years' experience of treatment with the 3-hydroxy-3-methylglutaryl coenzyme A
reductase inhibitor simvastatin in 45 hypercholesterolemic high-risk patients is
reported. All patients started with 20 mg simvastatin/day. The simvastatin dose
was increased to 40 mg in 22 patients. Fourteen patients needed further addition
of cholestyramine. Simvastatin reduced plasma cholesterol by 33% after 1 month
and was further reduced after adjustment of the lipid-lowering treatment. The
mean reduction in plasma cholesterol varied between 30% and 35% in 2 to 10 years.
Low-density lipoprotein cholesterol demonstrated mean reductions of 34% to 42%.
Mean plasma triglycerides were reduced by 26% after 1 month and by 1% to 19% the
following years. High-density lipoprotein (HDL) cholesterol increased initially
by 8% and remained elevated at 7% to 11% during the first 6 years, but then
dropped slightly below baseline. HDL2 cholesterol increased by 9% to 25% the
first 6 years and then decreased. HDL3 cholesterol showed a persistent elevation
during simvastatin treatment. About half of the subjects had minor transient but
clinical insignificant increases in creatine kinase. No cases of myopathy were
seen. Mean serum aspartate aminotransferase and alanine aminotransferase
increased significantly but within the normal ranges during the 10 years. The
tolerability and compliance of simvastatin treatment was excellent as judged from
patients' reports and from analyses of low-density lipoprotein cholesterol. This
10-year study demonstrates that simvastatin is an effective and safe drug with
excellent tolerability with only few minor side effects, and causes a pronounced
and persistent cholesterol-lowering effect during long-term treatment of
hypercholesterolemic patients at risk.
PMID- 10190518
TI - Cycling of inducibility of paroxysmal supraventricular tachycardia in women and
its implications for timing of electrophysiologic procedures.
AB - Arrhythmias in women may be affected by phases of the menstrual cycle. This study
was designed to determine the prevalence of perimenstrual clustering of
spontaneous episodes of paroxysmal supraventricular tachycardia (SVT) in women.
It also tested the hypothesis that women with this temporal pattern of events
have an altered probability of induction of paroxysmal SVT during
electrophysiologic testing at higher estrogen states (midcycle or with estrogen
replacement therapy) than at low estrogen states (perimenstrual or without
estrogen replacement). A structured history of the relation of spontaneous
paroxysmal SVTs to phases of the menstrual cycle was obtained prospectively among
42 women referred during a 3-year period. Patients with cyclical patterns of
spontaneous tachycardias, who had had negative electrophysiologic studies at
midcycle or while receiving estrogen replacement therapy, had repeat procedures
(1) when premenstrual or at the onset of menses, or (2) after stopping estrogen
replacement therapy. Seventeen of 42 consecutive female patients (40%) had
histories of perimenstrual clustering of arrhythmias. Six women (4 with normal
menstrual cycles, 2 on estrogen replacement therapy), who qualified for paired
electrophysiologic studies because of a negative initial electrophysiologic study
that included provocation with isoproterenol, had inducibility into SVTs during
the second study. All 6 had dual atrioventricular (AV) nodal pathway physiology,
4 had AV nodal reentrant tachycardia (AVNRT) induced, 1 had both AVNRT and
reciprocating AV tachycardias, and 1 had nonsustained AVNRT and an atrial
tachycardia induced. Successful ablation procedures were performed in 5 of the 6
patients. Thus, among women with a history of perimenstrual clustering of
paroxysmal SVT and among those receiving estrogen replacement therapy, scheduling
of elective electrophysiologic procedures at times of low estrogen levels
(premenstrual or off estrogen replacement therapy) may facilitate the probability
of a successful procedure.
PMID- 10190519
TI - Effects of age on outcome of tilt-table testing.
AB - Although neurally mediated syncope is thought to be common in the young and rare
in the elderly, there are few data evaluating the effects of age on the outcome
of tilt-table testing (TTT), especially in patients aged > or =80 years. We
examined the results of TTT in 352 subjects with unexplained syncope including
133 patients >65 years of age and 43 patients >80 years of age. The average age
was 54 +/- 20.8 years (range 11 to 99) and 51% were men. The TTT protocol
included at least 45 minutes of upright tilt in the drug-free state with or
without repeat TTT with isoproterenol or 15 minutes of upright tilt in the drug
free state followed by repeat TTT with isoproterenol. One hundred sixty-four
subjects (47%) had a positive TTT. As expected, there was an age-related decline
in positive TTT. A high proportion of elderly patients with unexplained syncope
had a positive TTT (37% of patients aged > or =65, and 23% patients aged > or
=80). Thus, TTT is a useful diagnostic test in patients aged > or =65 years with
unexplained syncope.
PMID- 10190520
TI - Value of sublingual isosorbide dinitrate before isoproterenol tilt test for
diagnosis of neurally mediated syncope.
AB - Head-up tilt-table test is valuable in diagnosing type of syncope. Sensitivity
varies in reports and is mostly poor. Isoproterenol or nitroglycerin is regularly
used to increase head-up tilt-table test sensitivity. The aim of this study was
to assess the value of sublingual isosorbide dinitrate administration before
isoproterenol tilt test as a simple, practical test for diagnosis of neurally
mediated syncope. Ninety-six patients (45 men and 51 women, mean age 42.5 years)
with recurrent (median 4 times) loss of consciousness that remained unexplained
after clinical and noninvasive assessment and 72 healthy volunteers (36 men and
36 women, mean age 40.1 years) were randomly divided into groups: isosorbide
isoproterenol test and isoproterenol test. During isosorbide-isoproterenol test,
a positive response (syncope in association with sudden hypotension or
bradycardia) occurred in 35 patients (72.9%) with unexplained syncope, an
exaggerated response (minor symptoms in association with slowly increasing
hypotension alone) occurred in 7 (14.6%), a negative response in 2 (4.2%), and
drug intolerance in 4 (8.3%). During isoproterenol testing, these percentages
were 52.1%, 16.7%, 25.0%, and 6.2%, respectively. Only 3 control volunteers
(8.3%) had a positive response to isosorbide-isoproterenol test and 2 (5.6%) to
isoproterenol test. The duration of the test and the time for syncope induction
in the isosorbide-isoproterenol test were shorter than those in the isoproterenol
test (24.84 +/- 5.15 vs 35.70 +/- 6.28 minutes [p <0.01]; 4.53 +/- 2.86 vs 6.27
+/- 4.11 minutes [p <0.05]). This study concluded that isosorbide-isoproterenol
test could be valuable in diagnosing unexplained syncope for its high
sensitivity, powerful specificity, and short duration.
PMID- 10190521
TI - New echocardiographic windows for quantitative determination of aortic
regurgitation volume using color Doppler flow convergence and vena contracta.
AB - Color Doppler images of aortic regurgitation (AR) flow acceleration, flow
convergence (FC), and the vena contracta (VC) have been reported to be useful for
evaluating severity of AR. However, clinical application of these methods has
been limited because of the difficulty in clearly imaging the FC and VC. This
study aimed to explore new windows for imaging the FC and VC to evaluate AR
volumes in patients and to validate this in animals with chronic AR. Forty
patients with AR and 17 hemodynamic states in 4 sheep with strictly quantified AR
volumes were evaluated. A Toshiba SSH 380A with a 3.75-MHz transducer was used to
image the FC and VC. After routine echo Doppler imaging, patients were
repositioned in the right lateral decubitus position, and the FC and VC were
imaged from high right parasternal windows. In only 15 of the 40 patients was it
possible to image clearly and measure accurately the FC and VC from conventional
(left decubitus) apical or parasternal views. In contrast, 31 of 40 patients had
clearly imaged FC regions and VCs using the new windows. In patients, AR volumes
derived from the FC and VC methods combined with continuous velocity agreed well
with each other (r = 0.97, mean difference = -7.9 ml +/- 9.9 ml/beat). In chronic
animal model studies, AR volumes derived from both the VC and the FC agreed well
with the electromagnetically derived AR volumes (r = 0.92, mean difference = -1.3
+/- 4.0 ml/beat). By imaging from high right parasternal windows in the right
decubitus position, complementary use of the FC and VC methods can provide
clinically valuable information about AR volumes.
PMID- 10190522
TI - Evaluation of the Sorin bicarbon bileaflet valve in 488 patients (519
prostheses).
AB - The Sorin bicarbon bileaflet prosthesis was introduced in 1990. To evaluate the
clinical performance of this prosthesis, we reviewed 519 prostheses that were
implanted in 488 patients (275 men, 213 women; mean age 59 years; SD 10.8, range
19 to 88) from 1993 to 1997. Preoperatively, 82% of patients were in New York
Heart Association (NYHA) functional class III or IV. There were 263 aortic valve
replacements (AVRs) (54%), 194 mitral valve replacements (MVRs) (40%), and 31
AVRs and MVRs (both) (6%). Concomitant procedures were performed in 82 patients
(17%). Follow-up was complete in 471 (97%) with a total cumulative follow-up of
866 patient-years. The 30-day mortality for patients with AVR was 5.7% (95%
confidence interval [CI] 2.9 to 8.5), MVR 17.5% (CI 9.9 to 19.7), and both 19%
(CI 7.6 to 51.1), with no early valve-related deaths. Patient survival at 55
months was 76% (SE 2.27%), with patients with AVR being 90%, MVR 63%, and both
61%. This was influenced by the following: (1) valve position, which was higher
for MVR (p = 0.0001); (2) poor NYHA functional class (p = 0.0006); (3)
reoperation (p = 0.02); and (4) age >70 years (p = 0.0001). Valve-related
complications (expressed as percentage per patient year and number of events)
were major thromboembolism at 0.9% per year (8), with AVR rates being 1.2% per
year (6) and MVR 0.7% per year (2); major hemorrhage at 2.3% per year (20) with
AVR rates being 2.4% per year (12) and MVR 2.5% per year (7); bacterial
endocarditis at 0.2% per year (2); and nonstructural dysfunction rate of 0.7% per
year (6). The reoperation rate was 0.9% per year (8) with AVR being 0.6% per year
(3) and MVR 1.7% per year (5). At 55 months, actuarial freedom from major
thromboembolism was 97% (SE 1.1%) with AVR being 96% and MVR 98%; major
hemorrhage 89% (SE 3.1%) with AVR being 88.6% and MVR 91%; structural valve
dysfunction 100% (SE 0.0%); and reoperation 97.1% (SE 1.10%) with AVR being 98.5%
and MVR 94.6%. At follow-up, 88% of survivors were in NYHA class I or II. In this
series, hospital mortality and overall survival in patients were influenced by
the patients' clinical characteristics. There were no early valve-related deaths.
Valve-related complications were similar to previously reported series with no
episode of structural failure. Our experience with the Sorin bicarbon bileaflet
prosthesis suggests that it has a satisfactory clinical performance, with low
complication rates.
PMID- 10190523
TI - Clinical course, microbiologic profile, and diagnosis of periannular
complications in prosthetic valve endocarditis.
AB - Whether periannular extension of prosthetic valve endocarditis (abscesses,
pseudoaneurysms, fistulas) is related to the etiologic agent, the clinical course
and the prognosis is still unknown. Likewise, transesophageal echocardiographic
accuracy in detecting periannular complications in prosthetic recipients remains
unsettled. We retrospectively analyzed data from 87 patients with anatomically
proven prosthetic valve endocarditis who underwent a transesophageal
echocardiographic examination. Periannular complications (30 abscesses, 18
pseudoaneurysms, 8 fistulas; 8 with >1) were found in 46 patients; results were
compared with the remaining 41 without complications. Transesophageal
echocardiography correctly identified 27 abscesses (90%) and all pseudoaneurysms
and fistulas. One diagnosis of pseudoaneurysm by echocardiography was not found
at surgery. No statistical differences were found regarding age, sex, type of
prosthesis (mechanical vs biologic), and etiologic agent. Periannular
complications were more frequent in aortic location (70% vs 20% in mitral
position; p <0.001) and in early (within 6 months after surgery) endocarditis
(63% vs 38% in late endocarditis; p = 0.04). The same percentage of patients from
both groups underwent surgery (98% with and 90% without complications). At
discharge, 62% and 67% of patients were alive, respectively. Thus, periannular
complications in prosthetic valve endocarditis are more frequent in aortic
location and within 6 months after surgery. Neither the type of prosthesis nor
the etiologic agent are related to the presence of periannular complications.
Short-term prognosis in patients who underwent surgery is not affected by the
presence of periannular complications.
PMID- 10190524
TI - Arrhythmia and survival in patients >18 years of age after the mustard procedure
for complete transposition of the great arteries.
AB - Increasing numbers of patients who underwent Mustard repair as children are now
adults. Loss of sinus rhythm, supraventricular arrhythmias, and sudden death have
been described in pediatric series. However, little is known about the clinical
course of adult patients. This retrospective cohort study examined 86 consecutive
adults (age >18 years) who had undergone the Mustard procedure and were referred
to an adult congenital cardiac clinic for ongoing follow-up. The incidence and
predictors of arrhythmia, congestive heart failure, and death were determined.
The median follow-up period was 8 years after age 18 or 23 years after Mustard
repair. There were 8 deaths (9%), 2 were sudden. Congestive heart failure (CHF)
requiring hospital admission occurred in 9 patients (10%). Pulmonary hypertension
and systemic ventricular dysfunction were independent risk factors for death or
CHF. Only 29 patients (34%) remained arrhythmia-free. Forty-one patients (48%)
had at least 1 episode of supraventricular tachycardia (SVT), with most patients
(30, 73%) having atrial flutter. SVT after the age of 18 was associated with CHF.
Pulmonary hypertension, systemic ventricular dysfunction, and junctional rhythm
before age 18 were independent risk factors for SVT. Pacemakers were implanted in
19 patients (22%); 13 of those were beyond age 18. Thus, adult survivors of the
Mustard procedure continue to be at risk for premature death, CHF and
supraventricular tachyarrhythmia.
PMID- 10190525
TI - Cardiac troponin T and I, echocardiographic [correction of electrocardiographic]
wall motion analyses, and ejection fractions in athletes participating in the
Hawaii Ironman Triathlon.
AB - Cardiac troponin T (cTnT) and troponin I (cTnI) are highly sensitive and specific
for detecting myocardial damage even in the presence of skeletal muscle injury.
In this study, we assessed whether ultraendurance exercise induced cardiomyocyte
injury using plasma cTnT and cTnI measurements, quantitative echocardiographic
wall-motion analysis, and ejection fraction measurement in athletes who
participated in the Hawaii Ironman Triathlon. Twenty-three athletes (11 men) who
completed the triathlon (3.9 km swim, 180.2 km bike, and 42.2 km run)
participated in this study. Blood samples were obtained 2 days before and
immediately after the triathlon for the determination of cTnT (Enzymun, Roche
Diagnostics) and cTnI (Dade Behring) concentrations. Quantitative
echocardiographic wall motion analysis and ejection fraction were obtained on 12
of the 23 participants before and immediately after the race. No subject had
detectable cTnT or cTnI or abnormal echo score before the race. Following the
race, 2 subjects (9%) had marked increases in both cTnT (0.15 and 0.33 microg/L)
and cTnI (2.09 and 4.44 microg/L). Four additional subjects (17%) had moderate
increases in cTnT (0.04 to 0.05 microg/L) but no detectable cTnI. Race time
correlated inversely with cTnT (r = -0.65, p <0.01). Mean change in the number of
abnormal echo segments after the race was 6.5 in those with a marked increase in
cTnT and cTnI, 2.3 in those with a moderate increase in cTnT, and 1.7 in those
with no increase. Ejection fraction decreased by an average of 24% after the race
(p <0.002). Thus, ultraendurance exercise may cause myocardial damage as
indicated by biochemical cardiac-specific markers and echocardiography. The
cellular nature of this damage and whether it is transient or permanent is
unclear at present.
PMID- 10190526
TI - Does diuretic therapy increase the risk of renal cell carcinoma?
AB - Several studies have suggested that systemic hypertension as a disease or its
therapy could increase the risk for malignancies. Diuretics reduce cardiovascular
morbidity and mortality and constitute a cornerstone in the antihypertensive
arsenal. To analyze the relation between diuretic therapy and the risk of
malignancies, we conducted a comprehensive review of pertinent previous
publications by searching the MEDLINE database for related articles in all
languages published between January 1966 and April 1998. Within the past decade,
we found 9 case control studies and 3 cohort studies in which the relation
between diuretic use and renal cell carcinoma was examined. In the case control
studies, the odds ratio of renal cell carcinoma occurring in patients treated
with diuretics averaged 1.55 with a 95% confidence interval of 1.42 to 1.71 (p
<0.00001) compared with nonusers of diuretics. In the 3 cohort studies of
1,226,229 patients, diuretic therapy was associated with a more than twofold risk
of renal cell carcinoma when compared with patients not on diuretics. In 1 cohort
study, and in the 7 case control studies in which the effects of gender were
reported, women had a higher odds ratio (2.01, confidence interval 1.56 to 2.67)
than men (1.69 confidence interval 1.34 to 2.13). Thus, cumulative evidence,
possibly stronger in women than in men, suggests that the long-term use of
diuretics may be associated with renal cell carcinoma. Although diuretics remain
the best documented drug class to reduce morbidity and mortality in systemic
hypertension, our data suggest a need for continued vigilance to assess the risk
benefit ratio of all drugs used for long-term therapy of cardiovascular
disorders.
PMID- 10190528
TI - I view with alarm (1999)
PMID- 10190527
TI - Diuretics and renal cell carcinoma.
PMID- 10190529
TI - Robert Anthony O'Rourke, MD: a conversation with the editor. Interview by William
Clifford Roberts.
PMID- 10190530
TI - Anti-ischemic effects of amlodipine in patients with stable angina pectoris and
myocardial ischemia during daily life. Amlodipine Study Group.
AB - Ambulatory electrocardiographic monitoring was used to assess the anti-ischemic
effects of amlodipine in a subset of 56 patients enrolled in a 14-week withdrawal
study; amlodipine therapy resulted in a marked decrease in the overall mean
number of ischemic events and the average number of transient ischemic episodes
(p <0.005). Amlodipine substantially reduced the number of ischemic events among
all patients during the single-blind phase, with further significant reductions
recorded among patients who remained on amlodipine during double-blind therapy,
but the number of ischemic events increased almost to baseline levels in patients
switched to placebo during double-blind therapy (p = 0.01 by analysis of
variance).
PMID- 10190531
TI - Attenuation of anti-ischemic efficacy during chronic therapy with nicorandil in
patients with stable angina pectoris.
AB - After 2 weeks of nicorandil therapy, time to ischemia on stress testing was
significantly less than on day 1 and not different from placebo. These data are
consistent with attenuation of the anti-ischemic effects of this drug and suggest
that the potassium channel-opening properties do not compensate for development
of attenuation to the nitrate component of nicorandil.
PMID- 10190532
TI - Effect of balloon material and inflation strategy on arterial trauma and
mechanisms of percutaneous transluminal coronary angioplasty as determined by
intracoronary ultrasound.
AB - Twenty-three patients were randomized to a minimally invasive strategy or to
standard percutaneous transluminal coronary angioplasty followed by intracoronary
ultrasound. There was no difference in intracoronary ultrasound-determined
dissection after the procedure in the 2 groups, and the mechanism of lumen
enlargement by percutaneous transluminal coronary angioplasty in both groups
predominantly was due to vessel stretch.
PMID- 10190533
TI - Long-term prognosis in women with normal dobutamine stress echocardiography.
AB - Although the long-term prognosis for patients with a normal dobutamine stress
echocardiographic result is good, most studies have focused on men. We assessed
the long-term cardiac prognosis for women by reviewing the cases of 100 women who
underwent dobutamine stress echocardiography for suspected coronary artery
disease and found that women with a normal result have an excellent long-term
cardiac prognosis.
PMID- 10190534
TI - Comparison of quality of life after coronary and/or valvular cardiac surgery in
patients > or =75 years of age with younger patients.
AB - Quality of life after cardiac surgery appeared to be comparable in patients aged
> or =75 years and younger patients. Preoperative depression had more impact on
postoperative well-being in the elderly compared with younger patients.
PMID- 10190535
TI - Effect of hormone replacement therapy on left ventricular hypertrophy.
AB - The mechanisms behind the reduction in cardiovascular morbidity and mortality in
postmenopausal women receiving hormone replacement therapy are not fully
understood. In this case-control study, we report a statistically significant
lower left ventricular mass in a group of elderly women who were receiving
hormone replacement therapy for >10 years than in age-matched controls.
PMID- 10190536
TI - Effectiveness and safety of alternate-day simvastatin and fenofibrate on mixed
hyperlipidemia.
AB - This randomized prospective clinical study evaluated the lipid-lowering effects
and safety of a new combination regimen in patients with mixed hyperlipidemia.
The data show that alternate-day simvastatin and fenofibrate therapy was as
effective as the standard daily combination of the same drugs at the same doses,
and it was safer, less expensive, and more tolerable.
PMID- 10190537
TI - Evaluation of left ventricular based pacing in patients with congestive heart
failure and atrial fibrillation.
AB - Acute hemodynamic data of left ventricular based pacing were assessed in 2 groups
of patients with severe cardiac failure: 11 patients with atrial fibrillation and
17 patients with sinus rhythm. Both biventricular and left ventricular pacing
significantly improved acute hemodynamic findings to a similar degree in both
groups, suggesting that left ventricular based pacing may be beneficial in
patients with severe cardiac failure regardless of whether or not they are in
sinus rhythm.
PMID- 10190538
TI - A new mutation in the elastin gene causing supravalvular aortic stenosis.
AB - A large supravalvular aortic stenosis kindred, with a point mutation in exon 18
and a stop codon in exon 22 of the elastin gene, is described. Clinically, the
disease severity appeared to increase in successive generations in this family.
PMID- 10190539
TI - Risk factors for new atherothrombotic brain infarction in older African-American
men and women.
AB - Independent risk factors for new atherothrombotic brain infarction (ABI) in older
African-American men were hypertension (risk ratio 4.381), diabetes mellitus
(risk ratio 2.872), and previous ABI (risk ratio 1.904). Independent risk factors
for new coronary events in older African-American women were cigarette smoking
(risk ratio 2.754), hypertension (risk ratio 5.914), diabetes mellitus (risk
ratio 3.464), serum total cholesterol (risk ratio 1.008), serum high-density
lipoprotein cholesterol (inverse association) (risk ratio 0.958), age (risk ratio
1.026), and previous ABI (risk ratio 2.601).
PMID- 10190540
TI - Rhabdomyolysis and renal failure associated with cerivastatin-gemfibrozil
combination therapy.
PMID- 10190541
TI - Conjugation of isoprene monoepoxides with glutathione, catalyzed by alpha, mu, pi
and theta-class glutathione S-transferases of rat and man.
AB - In the present study, the enzymatic conjugation of the isoprene monoepoxides 3,4
epoxy-3-methyl-1-butene (EPOX-I) and 3,4-epoxy-2-methyl-1-butene (EPOX-II) with
glutathione was investigated, using purified glutathione S-transferases (GSTs) of
the alpha, mu, pi and theta-class of rat and man. HPLC analysis of incubations of
EPOX-I and EPOX-II with [35S]glutathione (GSH) showed the formation of two
radioactive fractions for each isoprene monoepoxide. The structures of the EPOX-I
and EPOX-II GSH conjugates were elucidated with 1H-NMR analysis. As expected, two
sites of conjugation were found for both isoprene epoxides. EPOX-II was
conjugated more efficiently than EPOX-I. In addition, the mu and theta class
glutathione S-transferases were much more efficient than the alpha and pi class
glutathione S-transferases, both for rat and man. Because the mu- and theta-class
glutathione S-transferases are expressed in about 50 and 40-90% of the human
population, respectively, this may have significant consequences for the
detoxification of isoprene monoepoxides in individuals who lack these enzymes.
Rat glutathione S-transferases were more efficient than human glu tathione S
transferases: rat GST T1-1 showed about 2.1-6.5-fold higher activities than human
GST T1-1 for the conjugation of both EPOX-I and EPOX-II, while rat GST M1-1 and
GST M2-2 showed about 5.2-14-fold higher activities than human GST M1a-1a. Most
of the glutathione S-transferases showed first order kinetics at the
concentration range used (50-2000 microM). In addition to differences in
activities between GST-classes, differences between sites of conjugation were
found. EPOX-I was almost exclusively conjugated with glutathione at the C4
position by all glutathione S-transferases, with exception of rat GST M1-1, which
also showed significant conjugation at the C3-position. This selectivity was not
observed for the conjugation of EPOX-II. Incubations with EPOX-I and EPOX-II and
hepatic S9 fractions of mouse, rat and man, showed similar rates of GSH
conjugation for mouse and rat. Compared to mouse and rat, human liver S9 showed a
25-50-fold lower rate of GSH conjugation.
PMID- 10190542
TI - Biological fate of [14C]-1-nitropyrene in rats following intragastric
administration.
AB - 1-Nitropyrene (1-NP), a weak carcinogen associated with diesel exhaust particles,
has previously been detected in workplace atmospheres with in-use diesel engines
and in the general environment. In order to gain insight in its biological fate,
a single dose of [14C]-1-NP (27.6 microCi, 750 mg/kg body weight, b.w.) was
administered intragastrically to rats and the presence of metabolites in blood
and tissue homogenates, and radioactivity associated with blood proteins and
tissue DNA, were studied. Early peak levels of radioactivity observed in blood
and tissue homogenates indicated a rapid absorption of [14C]-1-NP from the
gastrointestinal tract. Metabolite patterns observed in plasma, liver and kidney
homogenates strongly suggested an important role of the intestinal microflora in
the enterohepatic recirculation, but not in nitroreduction of 1-NP prior to
absorption from the gastrointestinal tract. This might explain the low levels of
radioactivity associated with blood proteins, since 1-nitrosopyrene, a product of
nitroreduction of 1-NP, is likely to be involved in protein binding. Levels of
radioactivity associated with plasma proteins were approximately four times
higher than the levels of radioactivity associated with hemoglobin (401.0 and
84.1 pmol/g protein per micromol 1-NP kg b.w., respectively, at 24 h). Maximal
25% of the associated radioactivity was released following mild alkaline
hydrolysis of either hemoglobin or plasma proteins. 1-Aminopyrene was the only
released compound after hydrolysis of hemoglobin. In addition to 1-aminopyrene,
two more polar unidentified metabolites were detected following hydrolysis of
plasma proteins. Association of radioactivity with DNA was highest in the liver
at the first moments of observation (7.4 pmol 14C Eq./mg DNA per micromol 1-NP kg
b.w.), but decreased rapidly to levels lower than observed for kidney DNA (max.
3.0 pmol 14C Eq./mg DNA per micromol 1-NP kg b.w. at 24 h). In lungs 8-50 times
less radioactivity was associated with DNA than observed in the liver and
kidneys. The results of this study show, that 1-NP undergoes an extensive and
complex biotransformation in vivo, resulting in a variety of metabolites present
in blood and tissue homogenates and a diversity of blood protein adducts.
Concentrations of plasma metabolites, blood protein adducts and DNA adducts were
rather low. In addition, previous studies also showed relatively low
concentrations of metabolites present in urine. Therefore, sensitive and
selective methods will be needed in order to evaluate the biological fate of 1
NP, associated with diesel exhaust particles, in humans.
PMID- 10190543
TI - Expression of glutathione transferase isoenzymes in the porcine ovary in
relationship to follicular maturation and luteinization.
AB - The expression of different isoenzymes of glutathione transferase (GST), i.e. the
cytosolic subunits GSTA1/A2, A3, A4, A5, M1/2, M2 and P1, T2, and the microsomal
GST in follicles of different sizes and in corpora lutea from porcine ovary, was
investigated by Western blotting. No immunoreactivity was obtained with anti-rat
GSTT2 or anti-rat microsomal GST polyclonal antibodies. In contrast, GSTA1/A2,
A3, A4, A5, M1/2, M2 and P1 are all expressed in the cytosol from porcine
ovaries. In general, the highest levels of these GST isoenzymes were present in
the cytosol from corpora lutea, in agreement with measurements of activity
towards 1-chloro-2,4-dinitrobenzene. Immunoreactivity with anti-rat GSTP1 was
only obtained with follicles. The cytosolic GSTs from follicles and corpora lutea
were affinity purified on glutathione-Sepharose and separated by reversed-phase
high-performance liquid chromatography in order to quantitate the different
subunits. A peak corresponding to the class pi subunit was present in follicles.
This peak was also seen with corpora lutea, although at very low level. There
were four peaks containing class mu subunits. The remaining peaks were concluded
to contain the class alpha subunits, except for two peaks which are suggested to
contain proteins other than GSTs. The levels of the different subunits were
quantitated on the basis of the areas under the peaks and the relative amounts in
follicles of different sizes and in corpora lutea corresponded well with the
Western blot analysis.
PMID- 10190544
TI - Adducts with haemoglobin and with DNA in epichlorohydrin-exposed rats.
AB - Epichlorohydrin (1-chloro-2,3-epoxypropane; ECH) is an important industrial
chemical and a carcinogen in experimental animals. The main aims of the present
study were to characterize the adduct formation in female Wistar rats and to
identify adducts that could potentially be used in human biomonitoring studies.
The total binding of radioactivity to haemoglobin in rats administered 0, 0. 11,
0.22, 0.43, or 0.97 mmol [3H]ECH/kg body weight by i.p. injection, and sacrificed
24 h after treatment, was linearly related to a dose up to 0.43 mmol/kg body
weight. The binding at the highest dose was higher than predicted by
extrapolation from lower doses, indicating saturation of a metabolic process for
elimination of ECH. Ion-exchange chromatography of a globin hydrolysate showed
one major radioactivity peak corresponding to S-(3-chloro-2
hydroxypropyl)cysteine. The half-life of this adduct was estimated as about 4
days by analysis of globin from rats administered 0.43 mmol/kg body weight and
sacrificed after 1, 2 and 9 days. Crosslinking of the adduct, presumably with
glutathione, appeared to be the predominant secondary reaction. Hydrolysis of N
(3-chloro-2-hydroxypropyl)valine, the primary reaction product of ECH with N
terminal valine, would give N-(2,3-dihydroxypropyl)valine. A sensitive gas
chromatography/mass spectrometry method for the dihydroxypropyl adduct was used
to follow its formation and removal after administration of nonlabelled ECH (0.11
mmol/kg body weight). The level of this adduct reached a maximum of about 20
pmol/g globin after a few weeks, corresponding to about 0.1% of the initial
binding of ECH to globin. N-7-(3-Chloro-2-hydroxypropyl)guanine was detected in
rats administered 0.97 mmol [3H]ECH/kg body weight and sacrificed 6 h after
treatment. The adduct levels in haemoglobin and DNA were compared with previously
reported adduct levels in male Fischer 344 rats exposed to propylene oxide.
Despite its higher chemical reactivity, the capacity of ECH to alkylate
macromolecules in vivo was found to be somewhat lower than that of propylene
oxide.
PMID- 10190545
TI - Interactions of surface-confined DNA with electroreduced mitomycin C comparison
with acid-activated mitomycin C.
AB - The anticancer activity of the antineoplastic drug mitomycin C (MC) was
investigated using transfer stripping cyclic voltammetry (TSCV) with single
stranded DNA-modified hanging mercury drop electrode (HMDE). Reductive activation
of MC is necessary for drug covalent binding to DNA, and we have found that some
potential-controlled interactions of MC with DNA occur at the electrode, i.e. MC
can be activated by electroreduction. Acid and electroreductive MC activations
were compared and different adducts were subsequently generated, suggesting that
the drug can bind to DNA in more than one way. Under conditions of acid activated
MC, a monofunctional adduct between C-1 of MC and N-7 of guanine was formed on
the electrode surface, reduced at - 0.44 V (vs. SCE). However, when the DNA
modified electrode was immersed in a MC solution and potentials corresponding to
the quinone moiety reduction (- 0.3 V or more negative vs. SCE) were applied, an
intrastrand bifunctional adduct between C-1 and C-10 of MC and two N-7 of a pair
of adjacent guanines in ssDNA were formed at the electrode, reduced at - 0.49 V,
i.e. 50 mV more negative than the monoadduct. The results presented in this paper
show for the first time electrochemical detection of DNA-MC adducts at the
hanging mercury drop electrode.
PMID- 10190546
TI - Stability and DNA alkylation rates of the simplest functional analogues of CC
1065, para-hydroxy and para-amino phenethyl bromides.
AB - We have recently synthesised a series of compounds based on the simplest
functional unit of CC-1065 containing a para substituted phenethyl halide moiety.
These compounds alkylate N3 of adenines in a similar fashion to CC-1065, as well
as N7 of guanines to a limited extent. In this work we compared the para amino
substituted derivative (2) with the published hydroxyl compound (1) in terms of
stability, DNA reactivity and pH dependence using gel electrophoresis techniques.
The results show that 2 has a shorter lifetime and is at least 2.5 times more
reactive with DNA than 1. It is completely hydrolysed between 30 and 60 min in
buffer and its reaction with DNA is complete within 5 min. In contrast, only a
fraction of 1 is hydrolysed after 60 min and retains reactivity towards DNA even
after 3 h. The reactivities of both 1 and 2 with DNA are pH dependent and
reaction rates rapidly decrease in the range pH 5.8-8.8. Preliminary molecular
modelling studies suggest that the p-amino group on 2 enables the drug to bind to
the AT-rich minor groove more effectively, thus stabilising the orientation of
the substrate in the groove such that the reactive cyclopropyl ring is located
close to the nucleophilic centre N3 of adenine. A possible mechanism of action of
these drugs is presented based on these findings.
PMID- 10190547
TI - DNA adducts of heterocyclic amine food mutagens: implications for mutagenesis and
carcinogenesis.
AB - The heterocyclic amines (HCAs) are a family of mutagenic/carcinogenic compounds
produced during the pyrolysis of creatine, amino acids and proteins. The major
subclass of HCAs found in the human diet comprise the aminoimidazoazaarenes
(AIAs) 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4
dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethylimidazo[4,5
f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx)
and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). All, except DiMeIQx,
have been shown to be carcinogenic in animals. These compounds are present in
cooked muscle meats at the p.p.b. level. Since the discovery of the HCAs in the
late 1970s, many studies have examined the DNA adducts of these compounds. This
review compiles the literature on AIA-DNA adducts including their identification
and characterization, pathways of formation, mutagenesis in vitro and in vivo,
and their association with carcinogenesis in animal models. It is now known that
metabolic activation leading to the formation of DNA adducts is critical for
mutagenicity and carcinogenicity of these compounds. All of the AIAs studied
adduct to the guanine base, the major adduct being formed at the C8 position. Two
AIAs, IQ and MeIQx, also form minor adducts at the N2 position of guanine. A
growing body of literature has reported on the mutation spectra induced by AIA
guanine adducts. Studies of animal tumors induced by AIAs have begun to relate
AIA-DNA adduct-induced mutagenic events with the mutations found in critical
genes associated with oncogenesis. Several studies have demonstrated the
feasibility of chemoprevention of AIA tumorigenesis. Only a few studies have
reported on the detection of AIA-DNA adducts in human tissues; difficulties
persist in the routine detection of AIA-DNA adducts in humans for the purpose of
biomonitoring of exposure to AIAs. The AIAs are nevertheless regarded as possible
human carcinogens, and future research on AIA-DNA adducts is likely to help
address the role of AIAs in human cancer.
PMID- 10190548
TI - The peroxisome proliferator (PP) response element upstream of the human acyl CoA
oxidase gene is inactive among a sample human population: significance for
species differences in response to PPs.
AB - Peroxisome proliferators (PP) cause peroxisome proliferation, associated with
rodent hepatocyte growth perturbation and hepatocarcinogenesis. However, in
humans this class of non-genotoxic carcinogens does not appear to have the same
adverse effects. The peroxisome proliferator-activated receptor alpha (PPARalpha)
mediates the effects of PPs in rodents via peroxisome proliferator response
elements (PPREs) upstream of PP-responsive genes such as acyl coenzyme A oxidase
(ACO). When the human ACO promoter was cloned previously, it was found to be
active and to contain a consensus PPRE (-1918 AGGTCA C TGGTCA -1906). To confirm
and extend those original findings, we isolated a 2 kb genomic fragment of the
ACO gene promoter from a human liver biopsy and used it to create a beta
galactosidase reporter gene plasmid. The human ACO promoter reporter plasmid was
added to both Hepalclc7 and NIH 3T3 cells together with a plasmid expressing
mPPARa and assessed for its ability to drive PP-mediated gene transcription. The
human ACO promoter fragment was inactive, unlike the equivalent rat ACO promoter
fragment used as a positive control. The PPRE within our cloned fragment of the
human ACO promoter differed at three positions (5'-AGGTCA G CTGTCA-3') from the
previously published active human ACO promoter. Next, we studied the frequency of
the inactive versus the active human PPRE within the human population. Using a
PCR strategy, we isolated and analysed genomic DNA fragments from 22 unrelated
human individuals and from the human hepatoma cell line HepG2. In each case, the
PPRE contained the inactive sequence. These data show that the human ACO gene
promoter found in a sample human population is inactive. This may explain at the
genomic level the lack of response of humans to some of the adverse effects of
the PP class of non-genotoxic hepatocarcinogens.
PMID- 10190549
TI - Effect of hMSH6 cDNA expression on the phenotype of mismatch repair-deficient
colon cancer cell line HCT15.
AB - Mismatch recognition in human cells is mediated primarily by a heterodimer of
hMSH2 and hMSH6. Cells mutated in both alleles of the hMSH6 gene are deficient in
the correction of base/base mispairs and insertion/deletion loops of one
nucleotide and thus exhibit a strong mutator phenotype, evidenced by elevated
mutation rates and microsatellite instability, as well as by tolerance to
methylating agents. The decrease in replication fidelity associated with a loss
of mismatch correction implies that with each division, these cells are likely to
acquire new mutations throughout their genomes. Should such secondary mutations
occur in genes linked to replication fidelity or involved in the maintenance of
genomic stability, they might contribute to the observed mutator phenotype. The
human colon tumour line HCT15 represents one such case. Although it carries
inactivating mutations in both hMSH6 alleles, it has also been shown to contain a
missense mutation in the coding sequence of the proofreading domain of the
polymerase-delta gene. In an attempt to find out whether the phenotype of HCT15
cells was indeed brought about solely by the lack of hMSH6, we stably transfected
them with a vector carrying the wild-type hMSH6 cDNA. Our results show that
although the levels of transgenic hMSH6 were low, expression of the wild-type
protein resulted in a substantial restoration of mismatch binding, mismatch
repair capacity and the stability of mononucleotide repeats, as well as in the
reduction of mutation rates. Although methylation tolerance of the hMSH6
expressing cells was not markedly affected, the G2 cell cycle checkpoint, absent
in N-methyl-N'-nitro-N-nitrosoguanidine-treated control cells, was restored.
PMID- 10190550
TI - Cell proliferation in nasal respiratory epithelium of people exposed to urban
pollution.
AB - The nasal passages are a common portal of entry and are a prime site for toxicant
induced pathology. Sustained increases in regenerative cell proliferation can be
a significant driving force in chemical carcinogenesis. The atmosphere in Mexico
City contains a complex mixture of air pollutants and its residents are exposed
chronically and sequentially to numerous toxicants and potential carcinogens. We
were concerned that exposure to Mexico City's atmosphere might induce
cytotoxicity and increase nasal respiratory epithelial cell proliferation. Nasal
biopsies were obtained for DNA cell cycle analysis from 195 volunteers. The
control population consisted of 16 adults and 27 children that were residents in
a Caribbean island with low pollution. The exposed Mexico City population
consisted of 109 adults and 43 children. Sixty-one of the adult subjects were
newly arrived in Mexico City and were followed for 25 days from their arrival.
Control children, control adult and exposed Mexico City children all had similar
percentages of cells in the replicative DNA synthesis phase (S phase) of the cell
cycle (%S). A significant increase in %S in nasal epithelial cells was seen in
exposed adult residents in Mexico City biopsied at three different dates compared
with control adults. Newly arrived adults exhibited a control level of cell
turnover at day 2 after coming to the city. However, at days 7, 14 and 25 they
exhibited significant increases in %S. These data demonstrate an increased and
sustained nasal cell turnover rate in the adult population observable in as
little as 1 week of residence in Mexico City. This increase in cell proliferation
is in agreement with other reports of induced pathological changes in the nasal
passages of Mexico City dwellers. These observations suggest an increased
potential risk factor of developing nasal neoplasms for residents of large cities
with heavy pollution.
PMID- 10190551
TI - Cytotoxic and mutagenic response of mismatch repair-defective human cancer cells
exposed to a food-associated heterocyclic amine.
AB - The cytotoxic and mutagenic effects of 2-amino-1-methyl-6-phenylimidazo-[4,5-b]
pyridine (PhIP), a food-associated heterocyclic amine, were measured in three
human cancer cell lines possessing different mismatch repair (MMR) defects and in
matched cell lines corrected for the MMR deficiencies by specific chromosome
transfer. Cells deficient in MMR were more resistant to PhIP-induced cytotoxicity
and displayed approximately 3-fold more induced mutations at the hypoxanthine
guanine phosphoribosyl transferase locus. These results suggest that defects in
MMR carried by patients with hereditary nonpolyposis colorectal cancer syndrome
may result in enhanced sensitivity to certain dietary and environmental
carcinogens such as PhIP.
PMID- 10190552
TI - Recovery of RNA synthesis from the DHFR gene following UV-irradiation precedes
the removal of photolesions from the transcribed strand.
AB - It is thought that recovery of RNA synthesis following UV-irradiation is closely
related to the removal of UV-induced lesions from the transcribed strand of
active genes. To test this hypothesis, nascent RNA synthesis from three different
locations within the DHFR gene in CHO cells was assessed following exposure to UV
light (254 nm). Using both in vivo RNA labeling as well as the nuclear run-on
technique, it was found that RNA synthesis from the middle and the 3'-end of the
gene was inhibited within 20 min by approximately 30 and 70%, respectively, while
RNA synthesis from the 5'-end of the DHFR gene was enhanced. RNA synthesis from
the middle portion of the gene fully recovered within 30-45 min of post-UV
incubation, while recovery was slower from the 3'-end of the gene. Compared with
previously published data for the kinetics of removal of UV-induced DNA lesions
from the 5'-half of the DHFR gene in these cells, it is concluded that RNA
synthesis resumed significantly faster in this region than could be accounted for
by the removal of photolesions from the transcribed strand. Thus, although RNA
synthesis was initially inhibited by UV-induced photolesions, the results suggest
that RNA polymerase II was able to bypass these lesions prior to their removal.
PMID- 10190553
TI - Regulation of connexin32 and connexin43 gene expression by DNA methylation in rat
liver cells.
AB - Gap junction proteins (connexins) are expressed in a cell-specific manner and
expression is often reduced in neoplastic cells. We investigated the mechanisms
of connexin32 (Cx32) and connexin43 (Cx43) expression in hepatic cells using
MH1C1 rat hepatoma cells and freshly isolated, adult rat hepatocytes that express
Cx32 but not Cx43 and WB-F344 rat liver epithelial cells that express Cx43 but
not Cx32. Southern blotting after DNA restriction with MspI and HpaII indicated
that two MspI/HpaII restriction sites in the Cx32 promoter (positions -147 and
847) were methylated in WB-F344 cells, but not in MH1C1 cells or hepatocytes. In
contrast, an MspI/HpaII restriction site in the Cx43 promoter (position -38) was
methylated in MH1C1 cells, but not in WB-F344 cells or hepatocytes. Transient
transfection of the cell lines with connexin promoter-luciferase constructs
indicated that the Cx32 promoter was 7-fold more active in MH1C1 cells and the
Cx43 promoter was 5-fold more active in WB-F344 cells. These results suggest that
transcription of Cx32 and Cx43 in hepatic cells is controlled by promoter
methylation and by cell-specific transcription factors. Similar mechanisms may be
involved in the reduced expression of these genes frequently observed in
neoplastic cells.
PMID- 10190554
TI - Reactive oxygen species participate in mdr1b mRNA and P-glycoprotein
overexpression in primary rat hepatocyte cultures.
AB - P-glycoproteins encoded by multidrug resistance type 1 (mdr1) genes mediate ATP
dependent efflux of numerous lipophilic xenobiotics, including several anticancer
drugs, from cells. Overexpression of mdr1-type transporters in tumour cells
contributes to a multidrug resistance phenotype. Several factors shown to induce
mdr1 overexpression (UV irradiation, epidermal growth factor, tumour necrosis
factor alpha, doxorubicin) have been associated with the generation of reactive
oxygen species (ROS). In the present study, primary rat hepatocyte cultures that
exhibit time-dependent overexpression of the mdr1b gene were used as a model
system to investigate whether ROS might participate in the regulation of
intrinsic mdr1b overexpression. Addition of H2O2 to the culture medium resulted
in a significant increase in mdrlb mRNA and P-glycoprotein after 3 days of
culture, with maximal (approximately 2-fold) induction being observed with 0.5-1
mM H2O2. Furthermore, H2O2 led to activation of poly(ADP-ribose) polymerase, a
nuclear enzyme activated by DNA strand breaks, indicating that ROS reached the
nuclear compartment. Thus, extracellularly applied H2O2 elicited intracellular
effects. Treatment of rat hepatocytes with the catalase inhibitor 3-amino-1,2,4
triazole (2-4 mM for 72 h or 10 mM for 1 h following the hepatocyte attachment
period) also led to an up-regulation of mdrlb mRNA and P-glycoprotein expression.
Conversely, antioxidants (1 mM ascorbate, 10 mM mannitol, 2% dimethyl sulphoxide,
10 mM N-acetylcysteine) markedly suppressed intrinsic mdr1b mRNA and P
glycoprotein overexpression. Intracellular steady-state levels of the mdrl
substrate rhodamine 123, determined as parameter of mdr1-type transport activity,
indicated that mdr1-dependent efflux was increased in hepatocytes pretreated with
H2O2 or aminotriazole and decreased in antioxidant-treated cells. The induction
of mdr1b mRNA and of functionally active mdr1-type P-glycoproteins by elevation
in intracellular ROS levels and the repression of intrinsic mdrlb mRNA and P
glycoprotein overexpression by antioxidant compounds support the conclusion that
the expression of the mdr1b P-glycoprotein is regulated in a redox-sensitive
manner.
PMID- 10190555
TI - Overexpression of the human HAP1 protein sensitizes cells to the lethal effect of
bioreductive drugs.
AB - Abasic sites (AP sites) are generated in DNA either directly by DNA-damaging
agents or by DNA glycosylases acting during base excision repair. These sites are
repaired in human cells by the HAP1 protein, which, besides its AP-endonuclease
activity, also possesses a redox function. To investigate the ability of HAP1
protein to modulate cell resistance to DNA-damaging agents, CHO cells were
transfected with HAP1 cDNA, resulting in stable expression of the protein in the
cell nuclei. The sensitivity of the transfected cells to the toxic effect of
various agents, e.g. methylmethane sulfonate, bleomycin and H2O2, was not
modified. However, the transfected cells became more sensitive to killing by
mitomycin C, porfiromycin, daunorubicin and aziridinyl benzoquinone, drugs that
are activated by reduction. To test whether the redox function of HAP1 protein
was involved in this increased cytotoxicity, we have constructed a mutated HAP1
protein endowed with normal AP-endonuclease activity but deleted for redox
function. When this mutated protein was expressed in the cells, elevated AP
endonuclease activity was measured, but sensitization to the lethal effects of
compounds requiring bioreduction was no longer observed. These results suggest
that HAP1 protein, besides its involvement in DNA repair, is able to activate
bioreduction of alkylating drugs used in cancer chemotherapy.
PMID- 10190556
TI - Inhibition of benzo[a]pyrene-induced mutagenesis by (-)-epigallocatechin gallate
in the lung of rpsL transgenic mice.
AB - Epigallocatechin gallate (EGCG) is a major water-soluble component of green tea.
The antimutagenic activity of EGCG against benzo[a]pyrene (B[a]P)-induced
mutations was assessed by using transgenic mice carrying the rpsL gene as a
monitor of mutations. Seven-week-old male mice were given drinking water
containing EGCG for 3 weeks. On day 7, mice were treated with a single i.p.
injection of B[a]P (500 mg/kg body wt). Two weeks after the injection, the
mutations in the rpsL gene were analyzed. B[a]P treatment resulted in an
approximately 4-fold increase of mutation frequency at the rpsL gene in the lung.
An approximately 60% reduction in the B[a]P-induced mutations in the lung was
observed when mice were given EGCG at concentrations >0.005%. B[a]P-induced
mutations mainly occurred at G:C basepairs in the several specific nucleotide
sequences of the rpsL gene. These were AGG, CGG, CGT, TGG, TGC and GGT: all of
them contained a guanine residue. Mutations seen similarly in the human Ki-ras
codon 12 or p53 codons 157, 248, and 273 of lung tumor were also found in the
rpsL gene, and the mutations were suppressed by the EGCG treatment. In
conclusion, the antimutagenic effects of EGCG for B[a]P-induced mutagenesis in
vivo suggest that drinking green tea may reduce the tumor-initiating potency of
B[a]P in the lung.
PMID- 10190557
TI - Prevention by aspirin and its combination with alpha-difluoromethylornithine of
azoxymethane-induced tumors, aberrant crypt foci and prostaglandin E2 levels in
rat colon.
AB - The dose-response relationship in male F344 rats was determined for the ability
of aspirin administered in the diet to prevent azoxymethane (AOM)-induced colon
cancer and aberrant crypt foci (ACF) and to reduce prostaglandin E2 (PGE2)
levels. Starting at either 7 or 22 weeks of age, the rats received aspirin. All
rats received two doses of AOM (15 mg/kg each on days 7 and 14) and were killed
on day 36. The lowest concentrations of aspirin to prevent ACF or reduce PGE2
levels were 600 and 400 mg/kg, respectively. To evaluate the prevention of
tumors, rats received either 0 or 400 mg/kg aspirin for a total of 39 weeks with
AOM (30 mg/kg) administered 7 days after the start of treatment. Aspirin had no
effect on the yield of colon tumors. In a second experiment, rats started to
receive 0, 200, 600 or 1800 mg/kg aspirin or 1000 mg/kg alpha
difluoromethylornithine (DFMO) +/- aspirin. Eight and 15 days later, all the rats
received 15 mg/kg AOM. Eleven weeks later, animals that were receiving the
control diet started to receive 0, 200, 600 or 1800 mg/kg aspirin; 1000 or 3000
mg/kg DFMO; or 1000 mg/kg DFMO + 200 or 600 mg/kg aspirin. The animals were
killed 32 weeks later. DFMO effectively reduced the yield of colon tumors when
administered starting either before or after AOM while aspirin was much weaker.
The combination of aspirin + DFMO administered after AOM was synergistic. Both
aspirin and DFMO decreased the Mitotic Index, while apoptosis was increased only
by DFMO. Our results demonstrated that aspirin and DFMO could prevent colon
cancer when administered after AOM. Furthermore, aspirin reduced ACF, PGE2 levels
and mitosis at concentrations that did not prevent cancer. In contrast, the
ability to enhance apoptosis did correlate with the prevention of cancer.
PMID- 10190558
TI - HPLC/fluorescence determination of anti-BPDE-DNA adducts in mononuclear white
blood cells from PAH-exposed humans.
AB - The aim of this study was to compare (+/-)-r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10
tetrahydrobenzo[a]pyrene (anti-BPDE)-DNA adduct levels in groups of humans
subjected to various levels of polycyclic aromatic hydrocarbon (PAH)
(benzo[a]pyrene) exposure. An HPLC/fluorescence method was applied to detect
specifically anti-BPDE-DNA adducts in mononuclear white blood cells [lymphocyte
plus monocyte fraction (LMF)] from humans exposed to PAHs. A total of 130
subjects comprised the sample population: 26 psoriatic patients (3 days after
clinical coal tar treatment of the skin), 15 coke oven workers, 19 chimney
sweeps, 36 aluminium anode plant workers and 34 non-occupationally PAH-exposed
subjects (controls). PAH exposure was assessed in each group by means of the
urinary excretion of 1-pyrenol (mean group levels: 1.2, 0.7, 0.3, 65.0 and 0.1
micromol/mol creatinine in coke oven workers, chimney sweeps, aluminium plant
anode workers, psoriatic patients and non-occupationally PAH-exposed subjects,
respectively). HPLC/fluorescence analysis of BPDE-DNA adducts showed that the
percentage of subjects with adduct levels exceeding the 95 percentile control
subject value (8.9 adducts/10(8) nucleotides) was significantly high in coke oven
workers (46.7%) and chimney sweeps (21.0%) (chi2 test, P < 0.01 and P < 0.05,
respectively) but not in aluminium plant workers (11.1%) and psoriatic patients
(0%). The increase in BPDE-DNA adduct levels in LMF (Ln values) was significantly
related to chronic inhalatory and high PAH exposure (linear multiple regression
analysis, F = 6.37, P < 0.01; t = 4.2, P < 0.001). Skin acute (or short-term) and
high PAH exposure, charcoal-grilled meat consumption and smoking habit did not
seem to influence BPDE-DNA adduct formation in LMF.
PMID- 10190559
TI - Hprt mutant frequency and aromatic DNA adduct level in non-smoking and smoking
lung cancer patients and population controls.
AB - T cell cloning and 32P-post-labelling methods were used to study the mutant
frequency (MF) at the hypoxanthine-guanine phosphoribosyl transferase (hprt)
locus and the aromatic DNA adduct level (AL) in peripheral lymphocytes of newly
diagnosed lung cancer patients (92 ever-smokers and 87 never-smokers) and matched
population controls (82 ever-smokers and 79 never-smokers). Overall, the MF
(total mean 20.6 x 10(-6)) and AL (4.1 x 10(-8)) were similar in cases and
controls with the same smoking status, indicating that the disease has limited
effect on the two endpoints. When cases and controls were combined, the AL was
significantly higher in current smokers than in former or never-smokers (P =
0.0003) and the MF was significantly higher in ever-smokers than in never-smokers
(P = 0.004). Age affected the MF significantly in ever-smokers (1.6%/year, 95% CI
0.6-2.5, adjusted for pack-years and years since last smoking), especially among
cases (2.1%/year, 95% CI 0.5-3.7). An increase of AL with age was observed in
currently smoking cases only (2.3%/year, 95% CI 0.3-4.2, adjusted for smoking
dose). For currently smoking cases, there was also a more pronounced effect of
smoking dose on both endpoints and a significant correlation between AL and MF (r
= 0.52, P = 0.04) was observed among those with the highest dose. Our data also
provide additional evidence for the different turnover times of smoking-induced
DNA adducts and hprt mutations. The stronger increase of MF and AL with age and
dose in currently smoking patients compared with controls is consistent with an
interaction between smoking and genetic host factors.
PMID- 10190560
TI - Curcumin inhibits cyclooxygenase-2 transcription in bile acid- and phorbol ester
treated human gastrointestinal epithelial cells.
AB - We investigated whether curcumin, a chemopreventive agent, inhibited
chenodeoxycholate (CD)- or phorbol ester (PMA)-mediated induction of
cyclooxygenase-2 (COX-2) in several gastrointestinal cell lines (SK-GT-4, SCC450,
IEC-18 and HCA-7). Treatment with curcumin suppressed CD- and PMA-mediated
induction of COX-2 protein and synthesis of prostaglandin E2. Curcumin also
suppressed the induction of COX-2 mRNA by CD and PMA. Nuclear run-offs revealed
increased rates of COX-2 transcription after treatment with CD or PMA and these
effects were inhibited by curcumin. Treatment with CD or PMA increased binding of
AP-1 to DNA. This effect was also blocked by curcumin. In addition to the above
effects on gene expression, we found that curcumin directly inhibited the
activity of COX-2. These data provide new insights into the anticancer properties
of curcumin.
PMID- 10190561
TI - Potency of dietary indole-3-carbinol as a promoter of aflatoxin B1-initiated
hepatocarcinogenesis: results from a 9000 animal tumor study.
AB - Indole-3-carbinol (I3C), a metabolite of glucobrassicin found in cruciferous
vegetables, is documented as acting as a modulator of carcinogenesis and,
depending on timing and dose of administration, it may promote
hepatocarcinogenesis in some animal models. In this study we demonstrate that,
when given post-initiation, dietary I3C promotes aflatoxin B1 (AFB1)-induced
hepatocarcinogenesis in the rainbow trout model at levels as low as 500 p.p.m.
Trout embryos (approximately 9000) were initiated with 0, 25, 50, 100, 175 or 250
p.p.b. AFB1 by a 30 min immersion. Experimental diets containing 0, 250, 500,
750, 1000 or 1250 p.p.m. I3C were administered starting at 3 months and fish were
sampled for liver tumors at 11-13 months. Promotion at the level of tumor
incidence was statistically significant for all dietary levels, except 250 p.p.m.
Relative potency for promotion markedly increased at dietary levels >750 p.p.m.
We propose that more than one mechanism could be involved in promotion and that
both estrogenic and Ah receptor-mediated pathways could be active. The
estrogenicity of I3C, measured as its ability to induce vitellogenin (an estrogen
biomarker in oviparous vertebrates) was evident at the lowest dietary level (250
p.p.m.), whereas CYPIA (a P450 isozyme induced through the Ah receptor pathway)
was not induced until dietary levels of 1000 p.p.m. Therefore, at lower dietary
levels, promotion by I3C in this model could be explained by estrogenic
activities of I3C acid derivatives, as it is known that estrogens promote
hepatocarcinogenesis in trout. Much stronger promotion was observed at high
dietary I3C levels (1000 and 1250 p.p.m.), at which levels both CYP1A and
vitellogenin were induced.
PMID- 10190562
TI - Analysis of the inhibition of N-nitroso-dimethylamine activation in the liver by
N-nitro-dimethylamine using a new non-linear statistical method.
AB - N-nitro-dimethylamine (NTDMA) is carcinogenic to rats: it induces nasal cavity
tumours. It can be demethylated to N-nitromethylamine and formaldehyde and
reduced to N-nitroso-dimethylamine (NDMA): a potent liver carcinogen and also of
the nasal cavity if activation in the liver is blocked. To explain the mechanism
of NTDMA carcinogenicity we compared its demethylation with that of NDMA in liver
microsomes from female and male rats, untreated, fasted or treated with ethanol
to induce cytochrome P450 2E1 (CYP2E1). Kinetic parameters were analysed by
nonlinear statistical methods, which yielded unbiased parameter estimates for the
calculated Km and Vmax values. Km for both compounds was very similar in females
(24-47 microM) whereas Vmax for NTDMA was consistently higher than for NDMA as
substrate: 1.07-4.70 nmol formaldehyde/mg microsomal protein x min and 0.52-2.76
nmol, respectively. In liver microsomes from induced male rats NTDMA was found to
be a much more effective inhibitor of NDMA activation (KEI 39.6-73.6 microM) than
NDMA of NTDMA demethylation (KEI 224-286 microM). Nasal microsomes can
demethylate both NDMA and NTDMA but the kinetics are vastly different. NTDMA is
demethylated at a linear rate and approximately 10-fold more effectively than
NDMA. The mechanism of carcinogenicity of ingested NTDMA, we propose, is a
partial reduction to NDMA in the liver and inhibition of NDMA activation in the
liver by residual NTDMA, which enables NDMA to reach the nasal mucosa where it is
activated to DNA-alkylating species and the observed tumours are formed.
PMID- 10190563
TI - Overexpression of midkine in lung tumors induced by N-nitrosobis(2
hydroxypropyl)amine in rats and its increase with progression.
AB - The expression of midkine (MK) in lung tumors induced by N-nitrosobis(2
hydroxypropyl)amine (BHP) in rats was examined. The animals were administered
2000 p.p.m. of BHP in their drinking water for 12 weeks, then maintained without
further treatment until being killed 20-28 weeks after the beginning of the
experiment. MK mRNA expression of adenocarcinomas and squamous cell carcinomas
assessed by means of the reverse transcriptase-polymerase chain reaction and
northern blot analysis was significantly higher than in rat embryonic tissues
(positive controls) and contrasted strongly with the lack in normal lungs. MK
protein was detected immunohistochemically in 58.3% of alveolar hyperplasias,
92.3% of adenomas and 100% of adenocarcinomas and squamous cell carcinomas. The
extent of staining significantly increased along with malignant progression in
adenomatous (pre-)neoplastic lesions and tended to become more pronounced with
malignant progression in squamous lesions. The results suggest that MK may play
some essential roles in the development and progression of lung tumors induced by
BHP in rats.
PMID- 10190564
TI - Comparison of the DNA adducts formed by tamoxifen and 4-hydroxytamoxifen in vivo.
AB - Tamoxifen is a liver carcinogen in rats and has been associated with an increased
risk of endometrial cancer in women. Recent reports of DNA adducts in leukocyte
and endometrial samples from women treated with tamoxifen suggest that it may be
genotoxic to humans. One of the proposed pathways for the metabolic activation of
tamoxifen involves oxidation to 4-hydroxytamoxifen, which may be further oxidized
to an electrophilic quinone methide. In the present study, we compared the extent
of DNA adduct formation in female Sprague-Dawley rats treated by gavage with
seven daily doses of 54 micromol/kg tamoxifen or 4-hydroxytamoxifen and killed 24
h after the last dose. Liver weights and microsomal rates of ethoxyresorufin O
deethylation, 4-dimethylaminopyrine N-demethylation and p-nitrophenol oxidation
were not altered by tamoxifen or 4-hydroxytamoxifen treatment. Uterine weights
were decreased significantly and uterine peroxidase activity was decreased
marginally in treated as compared with control rats. DNA adducts were assayed by
32P-post-labeling in combination with HPLC. Two major DNA adducts were detected
in liver DNA from rats administered tamoxifen. These adducts had retention times
comparable with those obtained from in vitro reactions of alpha-acetoxytamoxifen
and 4-hydroxytamoxifen quinone methide with DNA. Hepatic DNA adduct levels in
rats administered 4-hydroxytamoxifen did not differ from those observed in
control rats. Likewise, adduct levels in uterus DNA from rats treated with
tamoxifen or 4-hydroxytamoxifen were not different from those detected in control
rats. These data suggest that a metabolic pathway involving 4-hydroxytamoxifen is
not a major pathway in the activation of tamoxifen to a DNA-binding derivative in
Sprague-Dawley rats.
PMID- 10190565
TI - Downregulation of DNA excision repair by the hepatitis B virus-x protein occurs
in p53-proficient and p53-deficient cells.
AB - Synergism between exposure to chemical carcinogens and infection with the
hepatitis B virus (HBV) has been implicated in the high incidence of
hepatocellular carcinoma. In this study we report that the HBV protein HBx,
inhibits cellular DNA repair capacity in a p53-independent manner. Two
alternative assays were used: the host cell reactivation assay, which measures
the cell's capacity to repair DNA damage in a reporter plasmid, and unscheduled
DNA synthesis, which measures the overall DNA repair capacity in damaged cells.
Two p53-proficient cell lines, the hepatocellular carcinoma cell line HepG2 and
liver epithelial cell line CCL13, were co-transfected with the pCMV-HBx reporter
plasmid and the pCMV-CAT plasmid damaged with UVC radiation. Compared with cells
transfected with control plasmid, the presence of HBx resulted in approximately
50% inhibition of the cell's capacity to reactivate CAT activity of UVC-damaged
plasmid, and approximately 25% inhibition of unscheduled DNA synthesis in cells
treated with either aflatoxin B1 epoxide or UVC radiation. Using the p53
deficient cell line Saos-2, we demonstrated that expression of HBx also resulted
in diminished overall cellular DNA repair of damage induced by both aflatoxin B1
epoxide and UVC radiation, using both the host cell reactivation and unscheduled
DNA synthesis assays. In summary, this study provides evidence for p53
independent regulation of DNA repair by HBx.
PMID- 10190566
TI - Tumor promotion by hydrogen peroxide in rat liver epithelial cells.
AB - Reactive oxygen species, including H2O2, play an important role in the tumor
promotion process. Using an in vitro model of tumor promotion involving the rat
liver epithelial oval cell line T51B, the tumor promoting activity of H2O2 in N
methyl-N'-nitro-N-nitrosoguanidine-initiated cells was studied. In this assay
system, the promoting effect of H2O2 is evidenced by the formation of colonies in
soft agar, appearance of foci in monolayer culture, disruption of gap junction
communication (GJC) in foci areas and growth at higher saturation densities. H2O2
preferentially induced the expression of c-fos, c-jun, c-myc and egr-1, while
JunB and JunD levels remained almost unchanged. H2O2 also induced
hyperphosphorylation of Cx43 and disruption of GJC. The effects of H2O2 on tumor
promotion, induction of immediate early (IE) genes and disruption of GJC are
blocked by antioxidants. These results suggest that H2O2 acts as a tumor promoter
in rat liver non-neoplastic epithelial cells and that the induction of IE genes
and disruption of GJC are two possible targets of H2O2 during the tumor promotion
process.
PMID- 10190567
TI - Promotion of intestinal carcinogenesis by dietary methionine.
AB - The metabolism of the polyamines spermidine and spermine is known to be enhanced
in rapidly proliferating cells. Methionine is a precursor of the aminopropyl
moieties of these amines. Therefore, it was of interest to study the effects of a
methionine supplemented diet on polyamine metabolism and preneoplastic changes
occurring in the intestinal tract of rats treated with the chemical carcinogen
azoxymethane (AOM). Adult Wistar rats received 15 mg AOM/kg body wt (i.p.) once
each week for 2 weeks. Thereafter, the rats were randomly divided into two groups
and received controlled isoenergetic diets containing the same amount of folate,
choline and vitamin B12 during 12 weeks: one group was kept on a standard diet;
the other was fed the same diet, except that 1% L-methionine was added at the
expense of carbohydrates. After 12 weeks, the administration of the methionine
supplemented diet stimulated the turnover rate of ileal epithelial cells,
indicating enhanced crypt cell proliferation. Furthermore, in this group, a 2
fold increase in the number of aberrant hyperproliferative crypts and the
appearance of tumors was observed in the colon. These effects were accompanied by
the increased formation of spermidine and spermine due to the enhancement of S
adenosylmethionine decarboxylase activity and by the upregulation of Cdx-1, a
homeobox gene with oncogenic potentials. The experimental data do not support the
view of a chemopreventive effect of dietary methionine supplementation on
intestinal carcinogenesis in rats, even at an early phase of preneoplastic
development, but rather suggest that methionine promotes intestinal
carcinogenesis.
PMID- 10190568
TI - Frameshift mutations in TGFbetaRII, IGFIIR, BAX, hMSH3 and hMSH6 are absent in
lung cancers.
AB - A genome-wide instability at simple repeat sequences characterizes
gastrointestinal and endometrial cancers of the microsatellite mutator phenotype
(MMP). The genes encoding transforming growth factor-beta receptor type II
(TGFbetaRII), insulin-like growth factor II receptor (IGFIIR), Bcl-2 associated X
protein (BAX), hMSH3 and hMSH6 have simple repeat sequences in their coding
regions. Consequently, mutations in the single repeat sequences in these genes
provide one major route for carcinogenesis in these cancers. We examined 43 non
small cell lung carcinomas and 16 small cell carcinomas for frameshift mutations
in simple repeat sequences of TGFbetaRII, IGFIIR, BAX, hMSH3 and hMSH6. In
addition, MMP was assessed using a primer set for BAT-26. None of 59 lung cancers
exhibited frameshift mutations or MMP. It is concluded that somatic frameshift
mutations in these genes and MMP do not constitute important mechanisms in lung
carcinogenesis. The possibility of some sort of genetic instability undetectable
as a form of MMP cannot be precluded.
PMID- 10190569
TI - SVPD-post-labeling detection of oxidative damage negates the problem of
adventitious oxidative effects during 32P-labeling.
AB - The exploitation of oxidative DNA lesions as biomarkers of oxidative stress in
vivo requires techniques that allow for the precise and valid measurement of
oxidative damage to DNA. Previously, endogenous levels of the oxidative lesion 8
hydroxy-2'-deoxyguanosine (8-HO-dG) in rat tissues determined by a micrococcal
nuclease/calf spleen phosphodiesterase-based 32P-post-labeling protocol were
found to be at least 10-fold higher than those determined by HPLC with
electrochemical detection. This was attributed to the adventitious oxidation of
the normal nucleotides (dGp) occurring during the labeling stage of the
postlabeling protocol, which could only be prevented by the introduction of
additional chromatographic steps to remove the unmodified species prior to
labeling. In the present study we report that an alternative snake venom
phosphodiesterase-based 32P-post-labeling procedure (SVPD-postlabeling) negates
the problem of adventitious oxidative damage during labeling by virtue of a
unique digestion strategy. In SVPD-post-labeling, digestion yields certain
lesions (thymine glycols, phosphoglycolates and abasic sites) as damage
containing dimer species which are ready substrates for labeling. In contrast,
the undamaged DNA is recovered as mononucleoside species (dN) which are not
substrates for labeling and so remain undetected. Furthermore, even if the
mononucleosides are oxidized during labeling, they will not contribute to the
level of damage detected. Indeed, we demonstrate that neither the external gamma
irradiation of the digested DNA samples nor increasing the incubation time of the
labeling reaction alters the levels of damage detected by SVPD-post-labeling. The
negation of adventitious oxidative effects during labeling deems that an
optimized SVPD-post-labeling procedure should be well-suited for the
biomonitoring of endogenous oxidative stress in vivo.
PMID- 10190570
TI - The relationship between 1,2-dimethylhydrazine dose and the induction of colon
tumours: tumour development in female SWR mice does not require a K-ras
mutational event.
AB - In this study we have investigated the relationship between the dose of 1,2
dimethylhydrazine (DMH) and the yield (and location) of tumours in a mouse strain
susceptible to colon tumour induction. Female SWR mice were injected with 6.8
mg/kg DMH i.p. once a week for 1, 5, 10 and 20 weeks and the animals were
followed for almost 2 years. Administration of increasing doses of DMH resulted
in a dose-dependent decrease in survival time. Colon tumours developed in 26, 76
and 87% of mice given a total dose of 34, 68 and 136 mg/kg DMH, respectively: no
tumours were detected in animals treated with a total dose of 6.8 mg/kg. Most
colon tumours (79%) were located in the distal colon with the remainder being
found in the mid colon and none were detected in either the proximal colon or
small intestine. As mutations in the K-ras gene are thought to be key events in
the pathogenesis of human and rodent colon tumours, we determined the frequency
of codon 12 and 13 K-ras mutations in these tumours by restriction site mutation
analysis and/or DNA sequencing. A total of 50 colon tumour samples were analysed
for codon 12 mutations and of these 29 were also screened for codon 13 mutations.
No mutations were detected in either of these codons. The mutational activation
of the K-ras gene is not an essential step in the development of DMH-induced
colon tumours in female SWR mice and if similar considerations apply to humans,
then the aetiological role of alkylating agents may be underestimated from the
prevalence of K-ras GC-->AT transitions in human tumours.
PMID- 10190571
TI - Synthesis, characterization and DNA modification induced by a novel Pt(IV)
bis(monoglutarate) complex which induces apoptosis in glioma cells.
AB - Programmed cell death or apoptosis is a mechanism for the elimination of cells
that occurs not only in physiological processes but also in drug-induced tumor
cell death. Thus, because cisplatin, cis-diamminechloroplatinum (II), produces
important damages on the DNA inducing apoptosis in several cell lines it has
become a widely used antitumor drug. However, cisplatin possesses some dose
limiting toxicities mainly nephrotoxicity. Pt(IV) complexes, such as iproplatin,
ormaplatin, and JM216 are a new class of platinum complexes that exhibits less
toxicity than cisplatin. Some of these complexes have shown significant antitumor
activity and a low cross-resistance to cisplatin. In the present paper, we have
analyzed the DNA binding mode and the cytotoxicity of a novel Pt(IV)-bis
(monoglutarate) complex. The data show that this novel complex produces DNA
interstrand cross-links to a higher extent and with a faster kinetics than
cisplatin. Also the Pt(IV)-bis (monoglutarate) complex kills glioma cells at drug
concentrations significantly lower than those of cisplatin. Interestingly, this
Pt(IV) complex produces in the glioma cells characteristic features of apoptosis
such as 'DNA laddering' and fragmented nuclei. Moreover, the p53 protein
accumulates early in glioma cells as a result of Pt(IV)-bis (monoglutarate)
treatment. These data indicate that the Pt(IV)-bis (monoglutarate) complex
induces apoptosis in glioma cells through a p53-dependent pathway.
PMID- 10190572
TI - Thioureas differentially induce rat hepatic microsomal epoxide hydrolase and
rGSTA2 irrespective of their oxygen radical scavenging effect: effects on
toxicant-induced liver injury.
AB - Thioureas have been employed as potent hydroxyl radical scavengers and also
inhibit production of oxygen free radicals. The in vitro oxygen radical
scavenging effect by N,N'-substituted thioureas including dimethylthiourea (DMT),
diethylthiourea (DET), tetramethylthiourea (TMT) and diphenylthiourea (DPT) was
assessed by the conversion of phi x-174 DNA from supercoiled DNA to the open
circular form or to fragmented DNA. Addition of the N,N'-substituted thioureas to
the incubation mixture significantly prevented a single strand breakage of phi x
174 DNA induced by autooxidation of benzenetriol. These thioureas were also
effective in preventing degradation of phi x-174 DNA induced by autooxidation of
benzenetriol in the presence of ferrous iron. In view of the in vitro radical
scavenging effect by the thioureas and the role of reactive oxygen species in the
induction of phase II detoxifying enzymes, expression of microsomal epoxide
hydrolase (mEH) and rGSTA2 in response to these agents was investigated in the
rat liver. Rats treated with each of the alkylthioureas exhibited marked
increases of mEH and rGSTA2 mRNA levels with TMT being the most effective. DPT an
arylthiourea, however, was minimally active in increasing the mRNAs. Time-course
studies revealed that DMT, DET and TMT increased the mRNA levels to the greatest
extent at 24 h after a single dose of treatment. The levels of mEH and rGSTA2
mRNA were elevated in a dose-dependent manner by the alkylthioureas. Immunoblot
analysis showed that the alkylthioureas induced mEH and rGSTA2 proteins in the
liver (0.6 mmol/kg per day, 3 days), which was consistent with the increases in
the mRNA levels. DMT, DET or TMT enhanced CCl4-induced liver toxicity, as
monitored by plasma aminotransferase activity, although each of the agents alone
caused only slight increase in the alanine aminotransferase activity. In contrast
to the effects of the alkylthioureas, DPT protected the liver against the
toxicant-induced injury. All of the thioureas prevented decreases in the hepatic
glutathione level by CCl4. Expression of cytochrome P450 2E1 and P450 2B1/2,
which are implicated with metabolic activation of CCl4, was assessed after
treatment with the thioureas. P450 2E1 and P450 2B1/2 were differentially induced
by the alkylthioureas with the expression of P450 2E1 being inversely related
with that of P450 2B1/2. These results showed that N,N'-substituted
alkylthioureas were capable of inducing mEH and rGSTA2 in the liver with
elevation of the mRNAs, that induction of mEH and rGSTA2 by these alkylthioureas
might be mediated by production of the reactive oxygens derived from metabolic
activation of the agents irrespective of their radical scavenging effect and that
the agents rather enhanced toxicant-induced liver injury with the induction of
P450 2E1 or P450 2B1/2.
PMID- 10190573
TI - Potency of various polycyclic aromatic hydrocarbons as inducers of CYP1A1 in rat
hepatocyte cultures.
AB - A number of highly toxic environmental pollutants including certain
polychlorinated dibenzo-p-dioxins (PCDD), polychlorinated dibenzofurans (PCDF),
and 'dioxin-like' polychlorinated biphenyls (PCB) are among the most potent
agonists of the aryl hydrocarbon receptor (AHR). Induction of cytochrome P4501A1
(CYP1A1) in mammalian cell culture is widely used as a functional parameter for
AHR activation providing an estimate for 'dioxin-like' inducing equivalents in
extracts from environmental samples. Since a number of polycyclic aromatic
hydrocarbons (PAHs) also act as AHR-agonists, the CYP1A1-inducing potencies,
measured as induction of 7-ethoxyresorufin O-deethylase (EROD) activity in rat
hepatocyte cultures were analyzed for 16 PAHs frequently present in environmental
samples. Among these, seven PAHs including benzo[a]pyrene were relatively potent
inducers allowing the determination of Induction Equivalency Factors (IEF). For
three PAHs including benzo[k]fluoranthene which acted as weak inducers, IEFs were
estimated, while six PAHs including acenaphthylene were classified as inactive.
Based on different efficacies the concentration-response characteristics of
CYP1A1 induction were analyzed in more detail for benzo[a]pyrene,
benzo[k]fluoranthene, and acenaphthylene. Benzo[k]fluoranthene was markedly less
effective than benzo[a]pyrene as inducer of EROD activity but even more effective
than benzo[a]pyrene as inducer of CYP1A1 protein and mRNA. Acenaphthylene was
highly more effective on the level of mRNA than on the levels of protein or EROD
activity. Further analysis revealed that the low efficacy of acenaphthylene as
inducer of CYP1A1 protein and EROD activity is due to its marked cytotoxicity
while no clear-cut explanation was found for the differences in efficacy between
benzo[k]fluoranthene and benzo[a]pyrene. The EROD-inducing potency of a mixture
of 16 PAH was about 2-fold higher than that calculated on the basis of IEFs of
the individual constituents of the mixture.
PMID- 10190574
TI - Urinary excretion of biomarkers for radical-induced damage in rats treated with
NDMA or diquat and the effects of calcium carbimide co-administration.
AB - The urinary excretion of seven aldehydes, acetone, coproporphyrin III and 8
hydroxy-2'-deoxyguanosine (8-OH-dG) as non-invasive biomarkers of oxidative
damage was measured in rats treated with diquat or N-nitrosodimethylamine (NDMA),
two compounds causing hepatic damage by different mechanisms. Furthermore, the
effect of co-administration of the aldehyde dehydrogenase inhibitor, calcium
carbimide (CC) on the urinary excretion of the aldehydes was determined. Slight
hepatotoxicity was found at the end of the experiment after treatment with NDMA
(0.5, 4 and 8 mg/kg at t = 0, 48 and 96 h, respectively) or diquat (6.8 and 13.6
mg/kg at t = 0 and 48 h, respectively). In diquat treated rats slight
nephrotoxicity was also found. Urinary excretion of aldehydes, acetone and
coproporphyrin III remained largely unchanged in rats treated with NDMA. In the
rats treated with diquat, the urinary excretion of several aldehydes was several
fold increased. An increase was also found in the urinary excretion of 8-OH-dG
after the second dose of diquat. Treatment of rats with CC did not significantly
influence the urinary excretion of aldehydes in control and NDMA rats. However,
in rats treated with diquat, CC caused a potentiating effect on the excretion of
acetaldehyde, hexanal and malondialdehyde (MDA), indicating that oxidation of
aldehydes to carbonylic acids by aldehyde dehydrogenases (ALDHs) might be an
important route of metabolism of aldehydes. In conclusion, increased urinary
excretion of various aldehydes, acetone, coproporphyrin III and 8-OH-dG was
observed after administration of diquat, probably reflecting oxidative damage
induced by this compound. No such increases were found after NDMA administration,
which is consistent with a different toxicity mechanism for NDMA. Therefore,
excretion of aldehydes, acetone, coproporphyrin III and 8-OH-dG might be used as
easily accessible urinary biomarkers of free radical damage.
PMID- 10190575
TI - 2,4-toluenediisocyanate and hexamethylene-diisocyanate adducts with blood
proteins: assessment of reactivity of amino acid residues in vitro.
AB - Diisocyanates, reactive compounds used in plastics industry and potent
occupational allergens, readily bind to proteins both in vitro and in vivo,
however, the pattern of adducts with individual amino acids has not been
investigated systematically. In this study, potential of the proteinogenic amino
acid residues for carbamoylation with 2,4-toluenediisocyanate (2,4-TDI) and
hexamethylenediisocyanate (HDI) was evaluated. The diisocyanates were incubated
in an in vitro system (buffer pH 7.4/dioxane 50:50) with: (a) a series of Nalpha
benzyloxycarbonyl amino acids (Z-amino acids) and N-acetylcysteine (Ac-Cys),
model compounds for non-N-terminal amino acids of the protein chain; (b)
dipeptides Val-Phe and Asp-Phe, model compounds for N-termini of globin and
albumin, respectively. Reactivity of the compounds tested, evaluated from their
depletion during incubation with the diisocyanates (measured by HPLC), was in the
order: Ac-Cys = Asp-Phe > Val-Phe = Nalpha-Z-Lys >> Nalpha-Z-His for 2,4-TDI, and
Ac-Cys > Asp-Phe > Val-Phe = Nalpha-Z-Lys > Nalpha-Z-His > N-Z-Tyr for HDI,
however, the adducts with Ac-Cys were unstable. Reactions of other amino acid
residues (e.g. Ser, Thr, Met, Trp, Arg, Asn, Gln) with 2,4-TDI and HDI were not
observed. Thus, N-terminal amino acids and Lys residues are likely to produce
most abundant adducts with diisocyanates in proteins. Further, three amino
compounds with increasing pKa values (Val-Phe, Val and Nalpha-Z-Lys) were
incubated with 2,4-TDI and N-acetyl-S-[4-(2-amino)tolylcarbamoyl]cysteine, a 2,4
TDI-derived thiocarbamate with carbamoylating activity, in media with 10% and no
dioxane, respectively. Here, reactivity of the amino compounds was decreasing in
the order: Val-Phe > Val > Nalpha-Z-Lys, which reflects the mechanism of the
amine-isocyanate reaction. The experiments also demonstrate the effect of a
solvent (organic phase content) on the yield of the carbamoylation reactions.
PMID- 10190576
TI - Deuterium isotope effects on noncovalent interactions between molecules.
AB - The topic of deuterium isotope effects is usually concerned with the effects on
chemical reactions that are caused by the substitution of deuterium atoms for
protium, or hydrogen, atoms in a molecule. These effects include changes in the
rate of cleavage of covalent bonds to deuterium, or to an atom located adjacent
to deuterium, in a reactant molecule. Deuterium isotope effects on other,
noncovalent, interactions between molecules are known to occur, but they are
generally considered to be insignificant, especially in biological experiments
where deuterium substituted molecules are used as tracers. Noncovalent
interactions between molecules include hydrogen bonding, and ionic and van der
Waals interactions. This article reviews evidence for deuterium isotope effects
on noncovalent interactions, with an emphasis on binding interactions between
molecules of biological interest, but also including examples of nonbiological
molecules in order to demonstrate the generality of these effects. The reality of
this effect relies on the assumption that the only difference between the
isotopomers considered is the presence of deuterium or hydrogen; there are no
impurities present. The physical basis of the effect may be due to differences in
the polarities and/or sizes of deuterated versus nondeuterated isomers, and the
extent of a deuterium isotope effect on a noncovalent interaction depends on the
site of deuteration within a biomolecule. The presence of this effect requires
careful interpretation of results obtained in experiments with deuterium labeled
compounds.
PMID- 10190577
TI - Effects of three epoxides--ethylene oxide, propylene oxide and epichlorohydrin-
on cell cycle progression and cell death in human diploid fibroblasts.
AB - Ethylene oxide (EtO), propylene oxide (PO), and epichlorohydrin (ECH) strongly
influenced the G1/S progression in human diploid fibroblasts, VH-10. However,
these epoxides did not affect substantially the G2/M progression. It was found
that G1 arrest is induced by these epoxides 6-18 h after the treatment at doses
above 5, 3, and 0.5 mMh for EtO, PO, and ECH, respectively. An inhibitory effect
on DNA synthesis was also demonstrated at the same doses within the same time
interval. On the contrary, the epoxides transiently stimulated DNA synthesis 3-18
h after the treatment with the lower doses (below 5, 3, and 0.5 mMh for EtO, PO,
and ECH, respectively). This effect was manifested both as an elevated rate of
DNA synthesis and as an increase in the number of cells in S-phase. Among the
three studied epoxides EtO was the most effective one: the increases of the rate
of DNA synthesis and of cells in S-phase were 35 and 55%, respectively. All the
epoxides tested induced significant decrease of intracellular level of reduced
glutathione (GSH) shortly after cell exposure. While low and moderate doses
induced a transient decrease in GSH level the high doses induced its irreversible
depletion. The extensive GSH depletion was related to cell death. Morphological
examination of cell nuclei indicated that epoxide-treated cells die via necrosis.
This conclusion is supported by the lack of such features of the apoptosis as
chromatin condensation and the occurrence of so called 'apoptotic bodies'. The
absence of nucleosomal fragmentation of DNA and an increase of the permeability
of the plasma membrane after the epoxide treatment also indicated a necrotic form
of cell death. ECH is about ten times more toxic than the two other epoxides, and
it causes almost 100% necrosis at dose of 3.0 mMh.
PMID- 10190578
TI - Effect of butylated hydroxyanisole on the toxicity of 2-hydroxy-1,4
naphthoquinone to rats.
AB - It has previously been shown that rats pre-treated with butylated hydroxyanisole
(BHA), a well-known inducer of the enzyme DT-diaphorase, are protected against
the harmful effects of 2-methyl-1,4-naphthoquinone. This is consistent with a
role for diaphorase in the detoxification of this quinone, but it is not known if
increased tissue levels of this enzyme give protection against other
naphthoquinone derivatives. In the present study, rats were dosed with BHA and
then challenged with a toxic dose of 2-hydroxy-1,4-naphthoquinone, a substance
that causes haemolytic anaemia and renal damage in vivo. Pre-treatment with BHA
had no effect upon the nephrotoxicity of 2-hydroxy-1,4-naphthoquinone, but the
severity of the haemolysis induced by this compound was increased in the animals
given BHA. DT-Diaphorase is known to promote the redox cycling of 2-hydroxy-1,4
naphthoquinone in vitro, with concomitant formation of 'active oxygen' species.
The results of the present experiment suggest that activation of 2-hydroxy-1,4
naphthoquinone by DT-diaphorase may also occur in vivo and show that increased
tissue levels of DT-diaphorase are not always associated with naphthoquinone
detoxification.
PMID- 10190579
TI - Carbamazepine induces multiple cytochrome P450 subfamilies in rats.
AB - We compared the effect of three different doses (30, 60, and 100 mg/kg) of
carbamazepine (CBZ) administered intraperitoneally for 1, 3, and 7 days on the
activity and protein content of hepatic cytochrome P450 (CYP) subfamilies in
Sprague-Dawley rats. After 3-day- and 7-day administration with CBZ, the total
CYP content had increased in a dose-dependent fashion. Among six enzyme
activities examined, only aniline hydroxylase activity remained unchanged after 7
day treatment with CBZ. Pentoxyresorufin O-deethylase activity showed the most
significant increase and was induced up to 7 days in a time-dependent fashion.
Pretreatment of rats with cycloheximide significantly suppressed the
pentoxyresorufin O-deethylase induction by one dose of 100 mg/day CBZ. Immunoblot
analysis showed a significant correlation between the protein content of each
isoenzyme examined and its activity except CYP2E1 after 7-day treatment with CBZ.
Similar results were obtained in the mRNA levels of CYP subfamilies. These
results suggested that CBZ may induce multiple CYP subfamilies, except CYP2E1,
and the activity and the protein content of CYP2B showed the greatest increase
with increased CYP2B mRNA.
PMID- 10190580
TI - Structure-function relationships of acid ribonucleases: lysosomal, vacuolar, and
periplasmic enzymes.
AB - It is surprising that only relatively recently has attention been directed to the
characterization of the properties of acid ribonucleases (RNases), leading to
some understanding of their biochemistry and their functional roles. The present
review summarizes current progress in this field under the following general
topics: (1) the wide distribution of acid RNases in organisms from viruses to
animals; (2) recent findings concerning their primary and three-dimensional
structure; (3) the structure-function relationship of acid RNases, with a fungal
RNase from Rhizopus niveus as a model enzyme; (4) the unique localization of acid
RNases in the periplasm of bacteria, vacuoles in plants, and lysosomes of animals
and protozoa; and (5) the diversity of physiological roles, depending on the
organism, such as self-incompatibility factors and defense proteins in some
plants, the surface protein of an animal virus related to pathogenicity, and
possible relationship to human cancer.
PMID- 10190581
TI - An overview of chemotherapeutic targets for antimalarial drug discovery.
AB - The need for new antimalarials comes from the widespread resistance to those in
current use. New antimalarial targets are required to allow the discovery of
chemically diverse, effective drugs. The search for such new targets and new drug
chemotypes will likely be helped by the advent of functional genomics and
structure-based drug design. After validation of the putative targets as those
capable of providing effective and safe drugs, targets can be used as the basis
for screening compounds in order to identify new leads, which, in turn, will
qualify for lead optimization work. The combined use of combinatorial chemistry-
to generate large numbers of structurally diverse compounds--and of high
throughput screening systems--to speed up the testing of compounds--hopefully
will help to optimize the process. Potential chemotherapeutic targets in the
malaria parasite can be broadly classified into three categories: those involved
in processes occurring in the digestive vacuole, enzymes involved in
macromolecular and metabolite synthesis, and those responsible for membrane
processes and signalling. The processes occurring in the digestive vacuole
include haemoglobin digestion, redox processes and free radical formation, and
reactions accompanying haem release followed by its polymerization into
haemozoin. Many enzymes in macromolecular and metabolite synthesis are promising
potential targets, some of which have been established in other microorganisms,
although not yet validated for Plasmodium, with very few exceptions (such as
dihydrofolate reductase). Proteins responsible for membrane processes, including
trafficking and drug transport and signalling, are potentially important also to
identify compounds to be used in combination with antimalarial drugs to combat
resistance.
PMID- 10190582
TI - Impediments to successful immunotherapy.
AB - Over the last decade, there has been a considerable increase in understanding of
immune responses against cancers, the antigenic structures on tumor cells
recognised by the immune system, and the development of more effective vaccines.
There is, however, very limited understanding of why the immune system most often
fails to control tumor growth and progression. In some patients, it is difficult
to demonstrate immune responses to their tumors, and it may be assumed that this
reflects poor recognition of tumor antigens, induction of anergy in lymphocytes,
or suppression of immune responses by tumor-derived factors. In other patients,
tumor progression appears to occur despite the presence of antibody or cell
mediated responses. This may indicate selection of tumor cells that have lost
tumor antigens or HLA antigens by immune responses against the tumor. Tumor cells
may also become resistant to mediators of apoptosis, such as Fas ligand and tumor
necrosis factor-related apoptosis-inducing ligand used by lymphocytes to kill
tumor cells. It is suggested that development of effective immunotherapy will
need to include strategies that take into account these limitations of immune
responses and classification of tumors according to the treatment approach most
likely to succeed.
PMID- 10190583
TI - Cancer vaccines: novel approaches and new promise.
AB - Cancer vaccines are a promising tool in the hands of the clinical oncologist. We
have summarized the most recent findings and achievements in this exciting field.
Tumor-associated antigens, as a basis for the new cancer vaccines, are reviewed.
We emphasize novel approaches for the design of safe and more effective vaccines
for cancer. We also discuss the possible clinical applications and the future
prospects for vaccine development.
PMID- 10190584
TI - Nervous control of blood flow in the orofacial region.
AB - The blood vessels of orofacial tissues are innervated by cranial parasympathetic,
superior cervical sympathetic, and trigeminal nerves, a situation somewhat
different from that seen in body skin. This review summarizes our current
knowledge of the nervous control of blood flow in the orofacial region, and
focuses on what we know of the respective roles of sympathetic, parasympathetic,
and trigeminal sensory nerves in the regulation of blood flow in this region,
with particular attention being paid to the mutual interaction between them.
PMID- 10190585
TI - Endoscopically guided midfacial degloving in infants for removal of congenital
and acquired midfacial masses.
AB - Midface degloving allows excellent exposure for a variety of congenital and
acquired pediatric facial masses. The petite facial skeleton of the infant and
child, however, can limit the utility of this dissection, thereby necessitating
external approaches and altered cosmesis. Endoscopic assistance can aid in safe
and complete removal of these masses without the need for external surgical
approaches. In this series, five infants underwent midfacial degloving for
midface lesions. Those masses that could not be adequately visualized underwent
midfacial degloving with endoscopic assistance. Successful surgical removal was
accomplished without complications, with follow-up ranging from 1 to 5 years. No
surgical nasal deformity, vestibular stenosis, or decrease in midfacial growth
was noted. Midfacial degloving with endoscopic guidance in selected cases is a
cosmetically appealing option for lesions not otherwise resectable by standard
midface degloving.
PMID- 10190586
TI - Acquired subglottic stenosis--depth and not extent of the insult is key.
AB - In contrast to skin, mucosal wound healing has not been extensively studied.
Subglottic stenosis (SGS) is an excellent model for such investigation. The main
objective of this pilot study was to develop a chronic model of SGS in a small
animal (i.e. rabbit). In so doing, a serendipitous observation was made that the
development of SGS is directly related to depth of the injury and is independent
of circumferential extent. Animals with deep injury (i.e. deep to the lamina
propria, reaching the perichondrium), independent of age and circumferential
extent, experienced respiratory obstruction resulting from edema and granulation
tissue formation and died or had to be sacrificed in the acute period. This was
in contrast to no risk of mortality in the more superficially injured group.
Histology was used to characterize this model of SGS. In the mucosal epithelium,
or mucosa, changes of inflammation, squamous metaplasia, basal cell hyperplasia,
necrosis and ulceration were only seen acutely and total regeneration of the
epithelium was achieved by the end of the study period. In contrast, changes
within the lamina propria, including chronic inflammatory cellular infiltrates
and fibroplasia, were lasting and resulted in fibrotic repair, not regeneration.
These findings are quite similar to the healing events in skin and suggest that
SGS is the mucosal equivalent of a 'keloid' or, perhaps more appropriately, a
'hypertrophic scar.' Likewise, cartilage degeneration and deformation were
persistent markers of the chronic phase of healing. Like the lamina propria, the
response to injury was reparative. Therefore, injury to the connective tissue is
a critical component of development of SGS.
PMID- 10190587
TI - Prevention and management of synechia in pediatric endoscopic sinus surgery using
dental wax plates.
AB - Synechia formation is a very common complication of endoscopic sinus surgery
(ESS). Inspite of meticulous post-operative care, synechia do form in quite a
large number of patients. Moreover, frequent post-operative cleaning may not be
possible without general anesthesia in non-compliant patients, especially
children. This study compares the incidence of synechia following pediatric ESS
with or without spacer/tamponade in the operated cavity. The authors have found
dental wax plates to be equally effective and more economical spacers compared to
Merocel tamponade, in prevention and management of synechia in the pediatric age
group.
PMID- 10190588
TI - Sensorineural hearing loss associated with otitis media with effusion in
children.
AB - Sensorineural hearing loss (SNHL) is known to occur in various types of otitis
media. Although the mechanism by which SNHL develops in association with otitis
media with effusion (OME) is unknown, several hypotheses have been advocated up
to now. We reviewed the clinical records of children with otitis media with
effusion (OME) to reveal the association with sensorineural hearing loss. The
material consisted of 71 children (119 ears) who were diagnosed as having OME and
gave reliable audiograms in our clinic during an 11 month period from February
1997 through January 1998. From these cases those which showed bone conduction
loss of 25 dB or higher at any one of the frequencies of 250 through 4 kHz were
selected and considered to be cases of SNHL. Eight cases (9%) which had temporary
threshold shift (TTS) or permanent threshold shift (PTS) were considered to be
etiologically related to OME. The clinical course in each of these cases with
SNHL was reviewed and evaluated in detail. We noted that all children with TTS
improved completely. The result of this study indicates that we have to be aware
of a possible development of SNHL during the course of OME.
PMID- 10190589
TI - Antibodies specific to outer membrane antigens of Moraxella catarrhalis in sera
and middle ear effusions from children with otitis media with effusion.
AB - OBJECTIVE: Recent studies have shown that bacterial DNA is present in a
significant percentage of middle ear effusions, suggesting that persistent
bacterial infection may be more important in pathogenesis and recurrence of
otitis media with effusion (OME) than previously considered. Although Moraxella
(M.) catarrhalis is one of the most common pathogens of otitis media, relatively
little is known about immune response to the organism. The objective of the
present study is to investigate how systemic and local immune activities against
M. catarrhalis may be associated with severity of OME. METHODS: The antibody
levels specific to outer membrane antigens of M. catarrhalis in sera and middle
ear effusions (MEEs) from 59 children with OME were measured by enzyme-linked
immunosorbent assay. Their ages ranged from 1 to 12 years with a median 5.0
years. The children were followed 1 year prospectively and classified into two
groups with or without recurrent/persistent OME according to severity of OME
during the follow-up 1 year. RESULTS: Serum IgG, IgM, and IgA antibodies specific
to outer membrane antigens of M. catarrhalis were detected in all samples and the
median levels were 35, 0.93, and 1.2 microg/ml respectively. The MEE IgG, IgM,
IgA, and secretory IgA antibodies were detected in over 95% samples tested and
the median levels were 371, 158, 20, and 50 ng/mg total protein respectively. A
comparison between acute and subacute/chronic phases revealed that the median
levels of MEE IgG and IgM antibodies were higher at the acute phase (692 vs. 340,
P = 0.06; 35 vs. 10, P = 0.02, respectively); while the MEE secretory IgA
antibody level was increased at the subacute/chronic phase (74 vs. 35, P = 0.02).
Either serum or MEE IgG antibody level was significantly lower in
recurrent/persistent OME group than that in nonrecurrent/non-persistent OME group
(13 vs. 43 ,microg/ml, P = 0.009; 238 vs. 577 ng/mg protein, P = 0.006,
respectively). CONCLUSIONS: These data provide additional information on the
immunologic aspects of children with OME. Decreased serum and MEE IgG antibody
levels specific to outer membrane antigens of M. catarrhalis may lead to failure
to eliminate this organism, resulting in persistent and/or recurrent appearance
of MEE.
PMID- 10190590
TI - Surgical approaches to antrochoanal polyps in children.
AB - Antrochoanal polyps (ACP) represent 4-6% of all nasal polyps in the general
population, but this proportion increases to 33% in the pediatric group. The aim
of this study is to discuss clinical and radiological findings, and some
different surgical approaches with their results in the pediatric patients. This
study consists of eight children with ACP diagnosed by means of clinical
examination, nasal endoscopy and computed tomography. One patient was treated
only with simple polypectomy. In five patients, transcanine sinuscopy (TS) was
added to functional endoscopic sinus surgery. Four of the patients underwent
anterior ethmoidectomy and uncinectomy. Middle meatal antrostomy was applied to
two of them. No recurrence was encountered within 5-30 months. The decision for
the appropriate type of surgery for ACP is influenced by factors such as
patient's age, other accompanying sinus pathologies, recurrence after previous
surgery, and the possibility of total excision. In patients carrying the risk of
recurrence, it is especially important to remove the polyp completely and manage
other sinus pathologies, as well as avoiding an unnecessarily expanded operation.
In selected patients, we believe that TS may be adequate in totally removing ACP.
PMID- 10190591
TI - The outcome after perinatal management of infants with potential airway
obstruction.
AB - Masses in the head and neck are being detected prenatally with increasing
frequency, necessitating the need for management of potential upper airway
obstruction at delivery. Establishment of the airway at delivery and its
maintenance thereafter are critical. This should optimally be performed with the
baby still attached to the placental circulation. The importance of
multidisciplinary team management, including a high risk obstetrician,
neonatologist, pediatric otolaryngologist, pediatric thoracic surgeon, and an
anesthetist, cannot be overemphasized. Endotracheal intubation is attempted
first, if unsuccessful then is followed by insertion of a rigid bronchoscope.
Tracheotomy should be reserved for airway obstructions, which are not amenable to
endotracheal intubation or in babies in whom exchange from a bronchoscope to
endotracheal tube cannot be safely performed. The management of six infants with
prenatally diagnosed potential airway obstruction is presented. Morbidity and
mortality still ultimately depend on the severity of the existent anomalies.
PMID- 10190592
TI - A novel approach to tracheostomal collapse: the use of an endoluminal Palmaz
stent.
AB - There are a number of surgical treatments for tracheostomal collapse of the
pediatric airway. The techniques include tracheoplasty with costal cartilage
graft, the placement of a tracheostomy tube and partial tracheal resection and
primary tracheal anastomosis to name a few. Since each child may possess unique
medical and social factors in additional to the tracheal pathology, the surgical
approach must be individualized. A case history of a 1-year-old Vietnamese child
with a tracheostomal collapse is presented. In this case, an endoluminal Palmaz
stent was placed endoscopically to support the collapsed tracheal segment for 3
months. After 3 months, the stent was removed, and the child has done well
without any airway intervention for 2 years. The indications for this novel
approach, the technique of insertion and removal of the stent are the focus of
this paper.
PMID- 10190593
TI - Facial paralysis: a presenting feature of rhabdomyosarcoma.
AB - The purpose of this paper is to present a child with embryonal rhabdomyosarcoma
involving the left middle ear, who initially presented with unilateral facial
paralysis. A 5-year-old boy presented with a 4-week history of left-sided facial
weakness, associated with persistent otitis media on that side. Examination
revealed complete left lower motor neuron facial weakness and hearing loss. A
myringotomy revealed a soft tissue mass behind the tympanic membrane. Biopsy and
oncologic assessment confirmed a stage II, group III left middle ear embryonal
rhabdomyosarcoma. Despite debulking surgery, local irradiation and multiple
chemotherapeutic courses the child deteriorated quickly. He developed
carcinomatous meningitis and died 9 months after his initial presentation. In
conclusion, middle ear tumors should be considered in the differential diagnosis
of unresolving otitis media, particularly when associated with persistent
ipsilateral facial paralysis. An ear mass, discharge, facial swelling, or
systemic symptoms may be initially absent despite the presence of this aggressive
malignancy. Careful examination of the middle ear is recommended in children with
facial weakness. A myringotomy incision may be necessary including a complete
assessment of the middle ear cavity, particularly when there is no fluid return.
PMID- 10190594
TI - Carpal tunnel topography during endoscopic decompression.
AB - The safety of the endoscopic technique for carpal tunnel release remains a major
concern. Serious complications such as division nerves, tendons or vessels may
occur. In this study the topography of the carpal tunnel was studied in fresh
cadaver hands after the introduction of the blade assembly of a one portal
system. By using a plastination method, it was possible to study the in situ
relationships in detail by serial cross sections. Furthermore a modified
Spalteholz method allowed the position of the blade to be viewed in whole
specimens.
PMID- 10190595
TI - Anthropometry and endoscopic carpal tunnel release.
AB - A prospective study was performed in 100 consecutive endoscopic carpal tunnel
releases (ECTR) to assess the effect of a number of anthropometric measures on
the ease of introduction of the ECTR system into the carpal tunnel. Ease of
access to the carpal tunnel correlated with the wrist circumference, height and
age of patients. Surgeons should be aware that ECTR is likely to be more
difficult in small patients with small wrists and should have a higher threshold
for conversion to the open technique to avoid neurological complications.
PMID- 10190596
TI - Does endoscopic carpal tunnel release have a higher rate of complications than
open carpal tunnel release? An analysis of published series.
AB - The purpose of this study was to evaluate the reported rate of complications
after endoscopic carpal tunnel release by means of an analysis of 54
publications, reporting a total of 9516 endoscopic and 1203 open releases.
Endoscopic release was comparable to open release in the rate of irreversible
nerve damage (0.3% and 0.2% respectively) but case reports may indicate a small
risk of unacceptable complications with endoscopy, such as transection of the
median nerve. Reversible nerve problems were more common after endoscopic
release. Tendon lesions were extremely rare (0.03%) and the rate of other
complications (reflex sympathetic dystrophy, haematoma, wound problems, etc.) was
about the same with endoscopic as with open release.
PMID- 10190597
TI - The usefulness of quantitative evaluation of three-phase scintigraphy in the
diagnosis of post-traumatic reflex sympathetic dystrophy.
AB - Quantitative analysis of three-phase bone scintigrams was done in 70 patients
with reflex sympathetic dystrophy (RSD) and in 30 patients who did not have RSD
after injury to the hand or wrist. Regions of interest were selected and the
uptake ratios (affected/unaffected) were calculated. Significant differences
between affected and unaffected patients were seen in the metacarpal area in
phase 2 of the scintigrams as well as in the metacarpophalangeal joints and
metacarpal bones in phase 3. Combination of these images had the greatest
diagnostic value. Sensitivity and specificity of 80% were achieved in the regions
of interest in phase 3. The duration of RSD and the predisposing injury
significantly affected the results of bone scintigraphy. It was also noted that a
fracture may cause increased fixation of the tracer in each phase of three-phase
bone scintigraphy in asymptomatic patients.
PMID- 10190598
TI - Fat suppression magnetic resonance imaging of the triangular fibrocartilage
complex. Comparison with spin echo, gradient echo pulse sequences and histology.
AB - Magnetic resonance imaging (MRI) of the triangular fibrocartilage complex (TFCC)
of the wrist was performed in ten healthy volunteers using spin echo T1-weighted
(SE-T1), fast spin echo T2-weighted (FSE-T2), gradient echo T2-weighted (GRE-T2)
and fat suppression spin echo T1-weighted (FS-T1) images. The images were
obtained in the coronal plane and were compared to the corresponding histological
coronal sections obtained from five fresh frozen cadavers. In our analysis, the
FS-T1 pulse sequence visualized the details of the TFCC best, followed by the GRE
T2 images. Delineation of the TFCC on the SE-T1 and the FSE-T2 was poor. The
coronal morphology of the TFCC represented on the fat suppression image was
almost identical to the corresponding histological sections. We conclude that the
fat suppression MRI clearly shows the complex structure of the TFCC and is useful
for the morphological evaluation of the TFCC.
PMID- 10190599
TI - Long-term functional results of wrist arthrodesis in rheumatoid arthritis.
AB - The purpose of this study was to evaluate the long-term effectiveness of wrist
fusion on the relief of pain and also the functional capacities of the upper
limbs in patients with rheumatoid arthritis (RA). Eighteen patients were assessed
at a mean of 7 years after wrist arthrodesis and a mean of 17 years after the
onset of RA. Radiological measurements, pain assessment and impairment rating of
the upper limbs were made of the fused and non-fused sides. The average position
of arthrodesis was 8 degrees of extension and 9 degrees of ulnar deviation. All
patients were pleased with the procedure and had satisfactory pain relief.
Impairment ratings did not detect any significant difference in the sensory and
motor function of the hand when the fused and non-fused groups were compared. We
conclude that in patients with rheumatoid arthritis, wrist arthrodesis is a
reliable procedure that provides predictable pain relief and a high degree of
satisfaction without additional functional loss in the upper limb.
PMID- 10190600
TI - Biaxial wrist replacement. Initial results in the rheumatoid patient.
AB - We report a short term review of 26 patients after Biaxial total wrist
replacement. The mean follow up was 33.6 months (range, 24-62). All except one
patient with psoriatic arthropathy had either seropositive or negative rheumatoid
arthritis. A significant improvement in the range of motion was obtained;
however, only 14 of 26 achieved a "functional" range. Eighteen obtained an
excellent or good result when graded using the Hospital for Special Surgery
score. Two radial and three carpal components showed radiolucent lines. Follow
up, however, was too short to determine whether this indicates progressive
loosening.
PMID- 10190601
TI - Hartmann's boutonniere: an anatomical study of digital neural loop penetrations
in the palm.
AB - We found neural loop penetrations by digital arteries in 47 of 51 dissected
palms. They were classified into four types according to morphology. The most
frequent type was observed in the proper digital nerves of the second to fourth
interdigital spaces just after branching from the common digital nerves. If
neural loop penetrations are not carefully identified at operation they may be
damaged and therefore it is important for hand surgeons to recognize the
existence of these structures.
PMID- 10190602
TI - The effect of the immunosuppressant FK 506 on peripheral nerve regeneration
following nerve grafting.
AB - Nerve allografts are highly antigenic and require the continuous use of
immunosuppressive drugs. Neurotoxic complications from immunosuppressant therapy
with FK 506 have been noted in the central and peripheral nervous system although
an increased rate of axonal regeneration has also been noted. Regeneration of
peripheral nerve grafts was assessed in a rat model clinically and
morphometrically after treatment for 2 and 6 weeks with two different doses of FK
506. Good regeneration was noted in all groups at 6 weeks. A significantly higher
axon count was observed in both the FK 506 groups after 2 weeks regeneration
compared with controls. This beneficial effect was not evident after 6 weeks of
regeneration. Whether this is related to a pruning mechanism or to a down
regulation of regenerative processes in the nerve due to possible neurotoxic
effects of FK 506 remains unknown.
PMID- 10190603
TI - Outcome of surgical treatment for forearm pronation deformities in children with
obstetric brachial plexus injuries.
AB - Seven children were operated on for pronation contractures of the forearm due to
obstetric brachial plexus injuries. All underwent extensive preoperative
evaluations to determine the extent of injury, secondary deformities, and
capacity to perform a few basic tasks. Sequential video studies were used to
document these findings. Operative procedures performed included various
combinations of tendon/muscle lengthenings and/or transfers. Postoperative
evaluations focused on function rather than gains in active range of motion and
the patient/parental assessment of the benefit of the procedure by response to a
questionnaire. All patients were followed for a minimum of I year following
surgery. The average gain in active supination was 45 degrees. Each patient
showed significant functional gains with a high degree of satisfaction.
PMID- 10190604
TI - Evaluation of restoration of extensor pollicis function by transfer of the
extensor indicis.
AB - The aim of this study was to assess long-term results of extensor indicis (EI) to
extensor pollicis longus (EPL) transfers and to assess donor site morbidity. A
specific EI-EPL evaluation method (SEEM) was used to measure EPL function after
transfer. The outcomes in 17 patients are presented. Results were assessed by the
Geldmacher score, the SEEM, mobility and strength of thumb and index finger,
pinch and grip strength, and a questionnaire, comparing the operated and non
operated hands. Based on the SEEM, the results were excellent to good in 11 of 17
patients. There was no marked loss of independent extension of the index finger
and only a 38% loss of extension strength.
PMID- 10190605
TI - Transfer of extensor carpi radialis longus or brevis for opponensplasty.
AB - For the restoration of thumb opposition many types of tendon transfer techniques
have been described. The flexor digitorum superficialis (FDS) of the ring finger
is commonly selected as a motor. On occasion, however, the quality of the flexor
muscles of the fingers or wrist is not good enough for tendon transfer and
another available muscle must be selected. In this situation, we have preferred
to use an extensor carpi radialis longus (ECRL) or brevis (ECRB) transfer to
restore opposition of the thumb. Follow-up examination, at an average 5 years and
10 months after operation, showed that the results of ten of 11 transfers were
excellent and the other was good.
PMID- 10190606
TI - Repair of zone 2 flexor pollicis longus lacerations in children.
AB - We reviewed seven thumbs in six children at a mean of 43 months after repair of
the flexor pollicis longus tendon in zone 2. Using the classification of Buck
Gramcko et al. (1976) the results were excellent in six and good in one.
PMID- 10190607
TI - The effect of pulsed electromagnetic fields on flexor tendon healing in chickens.
AB - This study was designed as a pilot investigation of the effect of pulsed
electromagnetic fields (PEMF) stimulation on early flexor tendon healing in a
chicken model using a similar stimulus to that used clinically. The PEMF used
caused a decrease in tensile strength and an increase in peritendinous adhesions.
PMID- 10190608
TI - A new prosthesis for the metacarpophalangeal joint. Study of materials and
biomechanics.
AB - This report discusses the Daphne prosthesis for the metacarpophalangeal joint on
the basis of the mechanical, chemical and biological performance of the materials
employed. The Daphne prosthesis is a mobile device. The main body is made of a
new generation polymethylmetacrylate, while the hinge is made of AISI 316 L
stainless steel. Biocompatibility tests were performed on the materials employed.
Systemic toxicity, cytotoxicity and contact tests have given favourable results.
Mechanical engineering tests have been used to investigate the performances and
reliability of the selected materials. The polymethylmetacrylate used in Daphne
behaves in a ductile fashion. No mechanical failures were encountered in fatigue
tests after 10 million cycles.
PMID- 10190609
TI - The Bone Tie. A new device for interfragmentary fixation.
AB - A new method of bone fixation is described, using a small stainless steel device
to provide compression between fragments with a single drill hole. The Bone Tie
uses an old architectural principle to hold bone fragments together with minimal
surgical dissection for access. The technique has been used in 14 cases, and the
results are presented. In ten cases the outcome was good. Complications were
encountered in four, mostly through technical error, although the final outcomes
were acceptable.
PMID- 10190610
TI - Surgical repair of acute collateral ligament injuries in digits with the Mitek
bone suture anchor.
AB - Eighteen acute grade III collateral ligament injuries were treated by using the
Mitek bone suture anchor. Seven were thumb metacarpophalangeal joint injuries,
and eleven were finger proximal interphalangeal joint injuries. Seventeen
patients were followed more than 12 months after surgery. All patients were able
to use the digits in daily living activities within 5 weeks after surgery, and
return to their original work or sports activities within 12 weeks. Pain was
completely relieved in 15 patients. Loss of joint motion averaged 7 degrees. In
all joints the postoperative lateral stress angle was within 10 degrees of that
of the contralateral digit.
PMID- 10190611
TI - Percutaneous intramedullary fixation of metacarpal shaft fractures.
AB - Twenty-two displaced metacarpal shaft fractures in 19 patients were stabilized
with multiple intramedullary K-wires. These were inserted percutaneously through
a small window in the base of the metacarpal and were buried in the bone. No
external splintage was routinely used postoperatively and all patients were
encouraged to mobilize their fingers immediately: formal physiotherapy was not
usually required. All the fractures that we were able to follow-up united, but
the K-wires bent at the fracture site in two instances, producing 20 degrees
angular deformities. The buried K-wires had to be removed in one instance as a
result of protrusion into the carpometacarpal joint.
PMID- 10190612
TI - Immobilization of the mallet finger. Effects on the extensor tendon.
AB - Since the mallet finger that is treated with isolated splinting of the distal
interphalangeal (DIP) joint can be moved freely proximal to the DIP joint, we
sought to determine whether such motion might cause a tendon gap that could
explain the extensor lag that often follows treatment. Experiments were performed
on 32 cadaveric fingers with open mallet finger lesions, immobilizing either the
DIP joint alone or both the DIP and PIP joints, while repeatedly flexing and
extending the more proximal finger and wrist joints. For each experiment, the gap
in the extensor tendon was measured. Joint motion proximal to the DIP joint and
retraction of the intrinsics did not cause a tendon gap in a finger with a mallet
lesion, supporting the convention that only the DIP joint needs to be
immobilized.
PMID- 10190613
TI - Percutaneous fixation of scaphoid fractures. An anatomical study.
AB - Percutaneous scaphoid fracture fixation has many advantages over the open method
of fixation. We describe the anatomical basis for a safe percutaneous approach.
Cannulated screws were inserted into 32 cadaveric scaphoids through 1 cm palmar
incisions under fluoroscopic control. We then measured the distance between the
entry point in the scaphoid and important local neurovascular structures. We also
measured the angle of entry of the guide wire in two planes. The mean distance of
the entry point from the main radial artery was 14 mm (range, 7-24 mm); from the
radial nerve 19 mm (range, 7-35 mm); from the recurrent branch of the median
nerve 29 mm (range, 14-45 mm); and from the superficial branch of the radial
artery 5 mm (range, 0-8 mm) The mean radial angle of insertion was 34 degrees and
the mean palmar angle of insertion was 58 degrees. Percutaneous fixation of
scaphoid fractures puts the superficial palmar branch of the radial artery at
risk. We recommend a 1 cm incision centred over the scaphotrapezial joint and
dissection under direct vision to the entry point in the scaphoid rather than a
completely percutaneous approach.
PMID- 10190614
TI - Closed reduction versus Kapandji-pinning for extra-articular distal radial
fractures.
AB - In a randomized prospective trial, treatment of extra-articular distal radial
fractures by closed reduction and plaster application was compared with Kapandji
pinning. Closed reduction and plaster cast was used in 50 patients, Kapandji
pinning in 48 patients. According to the Cooney score, good and excellent results
were found in the closed reduction and plaster cast group in 74%, compared with
75% in the Kapandji-pinning group. After measuring the maintenance of reduction
as well as the functional outcome at 1 year follow-up, no statistically
significant differences could be found between the two groups. We conclude that
both techniques can be used in treating extra-articular fractures of the distal
radius.
PMID- 10190615
TI - Radiocarpal fracture-dislocation.
AB - Radiocarpal fracture-dislocation is an uncommon but complex injury that is often
the result of high energy trauma. The combination of ligamentous and osseous
injuries demands meticulous attention to restoration of anatomy, especially of
the radial styloid. Open reduction and internal fixation is often necessary to
restore the relationship of the end of the radius to the carpus and distal ulna.
We present a retrospective review of 12 patients treated over a 10-year period
and review the literature.
PMID- 10190616
TI - The operative treatment of intraarticular Smith fractures.
AB - Twenty-one intraarticular palmar displaced fractures of the distal radius
operated on between 1990 and 1995 were reviewed with a mean follow-up of 27.3
months (range, 8-54). Fifteen fractures were treated with palmar T-plates, two in
combination with an external fixator. Five fractures were treated with external
fixators and K-wires, and one fracture was treated with percutaneous K-wires and
a cast. In six patients cancellous bone graft from the iliac crest was used. The
most satisfactory clinical and radiological results were obtained by anatomical
reconstruction of the articular surface. The favoured method remains
stabilization with palmar T-plates. K-wires with a cast should only be used in
simple articular fractures with a large palmar fragment.
PMID- 10190617
TI - A prospective study of two conservative treatments for ganglia of the wrist.
AB - This randomized prospective study assessed whether multiple puncture of the
ganglion wall improves the results of simple ganglion aspiration. We found that
32% of ganglia resolved after aspiration alone in comparison with 22% after
aspiration and multiple puncture. This difference was not significant. However,
only 18% of patients requested formal surgical excision, suggesting that
aspiration allays fears of malignancy and allows the patient to accept a minor
cosmetic embarrassment.
PMID- 10190618
TI - The effect of dorsal carpal ganglion excision on the scaphoid shift test.
AB - A clinical and radiographic review was performed on 18 patients (19 wrists) with
dorsal carpal ganglia and associated positive scaphoid shift test. All patients
underwent excision of the ganglion followed by 2 weeks of postoperative
immobilization with the wrist in 20 degrees extension. All patients had wrist
pain, a painful clunk on the Watson scaphoid shift test, localized tenderness on
palpation of the scapholunate articulation and normal radiographs. Patients were
assessed postoperatively by questionnaire and physical examination. Improved
functional activity and decreased pain were noted in all patients. In 17 of 19
wrists, the positive preoperative Watson scaphoid shift test become negative. We
believe that dorsal wrist ganglia are frequently associated with a positive
scaphoid shift test and that excision of the ganglion followed by 2 weeks
immobilization may lead to resolution of the signs and symptoms of instability,
at least in the short term.
PMID- 10190619
TI - Sintered bone implantation for the treatment of benign bone tumours in the hand.
AB - We report the results of treatment of benign bone tumours in the hand with
curettage and sintered bone implantation using bovine sintered bone (True Bone
Ceramics). There were 22 patients who underwent sintered bone implantation in our
department in 1984 or later. The follow-up survey period varied from 9 months to
11 years and 2 months (mean, 5.8 years). Recurrence of tumours and complications
such as infection or fracture were not observed, and there were no clinical
symptoms. X-rays revealed new bone formation connecting the implanted blocks to
bone. Sintered bone was not absorbed, and lucent zones around the implants or
other abnormal findings were not observed. Bone union was achieved in all
patients who had pathological fractures before surgery.
PMID- 10190620
TI - Recurrent benign chondroblastoma at the distal end of the radius.
AB - We report a 13-year-old boy with a rapidly recurring benign chondroblastoma in
the epiphysis of the distal end of the radius.
PMID- 10190621
TI - The "plastic bag syndrome". Compression of the digital neurovascular bundles by
commercial plastic bags.
AB - We report a condition we call the "plastic bag syndrome" in which pressure on the
neurovascular bundles causes temporary ischaemia in the distal part of the finger
together with a neuropraxia of the digital nerves. Although in most cases the
discomfort or numbness is fleeting, requires no medical assistance and is readily
forgotten, in some instances the symptoms are such that medical advice is sought.
Since the injury can lead to permanent damage and subsequent limitation in the
use of the finger, we believe that the public should be advised to take simple
precautions to prevent it from happening.
PMID- 10190622
TI - An improved method of ring removal.
AB - A number of techniques exist for the removal of rings from swollen fingers. An
improved method is described using ribbon gauze and a paper clip. It is cheap,
quick and effective and can be used in the presence of minor lacerations and
abrasions.
PMID- 10190623
TI - Onychomatricoma.
AB - We report a case of onychomatricoma, which is a rare benign tumour originating in
the germinal matrix of the nail. The diagnosis can be made on the typical
clinical findings and confirmed by histology. Complete excision is the treatment
of choice.
PMID- 10190624
TI - Granular cell tumour of the ulnar nerve.
AB - Although granular cell tumours have been demonstrated to have a neural origin,
they rarely arise in peripheral nerve trunks. We report a case of granular cell
tumour of the ulnar nerve in a 51-year-old man. Though dissectable from the
nerve, this intraneural tumour showed microscopic involvement of focal nerve
fibres. This tumour tended to infiltrate the nerve in the same manner as a
neurofibroma.
PMID- 10190625
TI - Posterior interosseous nerve syndrome due to pseudogout.
AB - Posterior interosseous nerve palsy associated with pseudogout of the elbow joint
in a 71-year-old woman is described. Local steroid injection and administration
of a nonsteroidal anti-inflammatory drug was effective in treatment.
PMID- 10190626
TI - Myositis ossificans of the hand.
AB - We present a case of myositis ossificans of the hand and review the clinical,
radiological, and histological presentation, as well as the appropriate
therapeutic management.
PMID- 10190627
TI - A glomus tumour with four recurrences.
AB - A case of a glomus tumour of the distal segment of the ring finger, with four
apparent recurrences in an 8-year period, is described. The patient was treated
by two different surgeons (two and three times respectively) and obtained pain
free intervals of between 4 and 11 months before recurrence. Histological
examination confirmed the diagnosis of a glomus tumour in all five procedures.
The location of the glomus tumour was defined preoperatively by high resolution
MR imaging.
PMID- 10190628
TI - Painless osteoid osteoma in a metacarpal.
AB - Osteoid osteoma is a benign primary tumour of bone occurring in the first two
decades of life. It presents with pain and is uncommon in the hand, particularly
so in the metacarpals. We report a painless osteoid osteoma affecting a
metacarpal.
PMID- 10190629
TI - Lymphangiosarcoma in chronic lymphoedema. Stewart-Treves syndrome.
AB - A case of post-mastectomy lymphangiosarcoma is reported. Lymphangiosarcoma is an
extremely rare but highly lethal complication of chronic lymphoedema. Our patient
was treated by amputation and died 6 months later. Treatment of post-mastectomy
lymphangiosarcoma is still unsatisfactory. Early recognition and radical ablative
surgery seem to provide best chance for survival.
PMID- 10190630
TI - Lymphoedema and hand surgery.
AB - We report the case of a woman with a previous history of breast carcinoma,
treated with a left radical mastectomy and axillary clearance, who developed
lymphoedema in the left arm following a carpal tunnel decompression complicated
by a superficial wound infection.
PMID- 10190631
TI - Conservative versus operative treatment for Kienbock's disease. A retrospective
study.
PMID- 10190632
TI - Radial tunnel syndrome.
PMID- 10190633
TI - An introduction to: honoring the life and work of Sol Levine.
PMID- 10190634
TI - Issues in promoting health.
AB - Policymakers in many countries seek to contain health care costs over the long
range by promoting health and more effective health behavior. Such efforts can be
directed at entire populations, at members of a health plan, at defined risk
groups or single individuals at risk. Many health risks are associated with socio
economic status and social inequalities but these are often difficult to address
because of social and political conflicts. Health, also, is often a product of
culture and other social circumstances. Health may be promoted through non-health
interventions or through more targeted health efforts seeking to effect behavior
change. Preventive screening is of growing importance but such efforts often out
pace evidence of efficacy or cost-effectiveness. Many opportunities exist to
build on new clinician-patient partnerships to make patients better informed and
to effect positive health behavior. New technologies, and particularly the
internet, offer new ways to promote health and more constructive illness
behaviors.
PMID- 10190635
TI - Crime: social disorganization and relative deprivation.
AB - Crime is seldom considered as an outcome in public health research. Yet major
theoretical and empirical developments in the field of criminology during the
past 50 years suggest that the same social environmental factors which predict
geographic variation in crime rates may also be relevant for explaining community
variations in health and wellbeing. Understanding the causes of variability in
crime across countries and across regions within a country will help us to solve
one of the enduring puzzles in public health, viz. why some communities are
healthier than others. The purpose of this paper is to present a conceptual
framework for investigating the influence of the social context on community
health, using crime as the indicator of collective wellbeing. We argue that two
sets of societal characteristics influence the level of crime: the degree of
relative deprivation in society (for instance, measured by the extent of income
inequality), and the degree of cohesiveness in social relations among citizens
(measured, for instance, by indicators of 'social capital' and 'collective
efficacy'). We provided a test of our conceptual framework using state-level
ecologic data on violent crimes and property crimes within the USA. Violent
crimes (homicide, assault, robbery) were consistently associated with relative
deprivation (income inequality) and indicators of low social capital. Among
property crimes, burglary was also associated with deprivation and low social
capital. Areas with high crime rates tend also to exhibit higher mortality rates
from all causes, suggesting that crime and population health share the same
social origins. Crime is thus a mirror of the quality of the social environment.
PMID- 10190636
TI - Aggregation and the measurement of income inequality: effects on morbidity.
AB - This is a cross-sectional study using records from the National Health Interview
Survey linked to Census geography. The sample is restricted to white males ages
25-64 in the United States from three years (1989-1991) of the National Health
Interview Survey. Perceived health is used to measure morbidity. Individual
covariates include income-to-needs ratio, education and occupation. Contextual
level measures of income inequality, median household income and percent in
poverty are constructed at the US census county and tract level. The association
between inequality and morbidity is examined using logistic regression models.
Income inequality is found to exert an independent adverse effect on self-rated
health at the county level, controlling for individual socioeconomic status and
median income or percent poverty in the county. This corresponding effect at the
tract level is reduced. Median income or percent poverty and individual
socioeconomic status are the dominant correlates of perceived health status at
the tract level. These results suggest that the level of geographic aggregation
influences the pathways through which income inequality is actualized into an
individuals' morbidity risk. At higher levels of aggregation there are
independent effects of income inequality, while at lower levels of aggregation,
income inequality is mediated by the neighborhood consequences of income
inequality and individual processes.
PMID- 10190637
TI - Gender matters: an integrated model for understanding men's and women's health.
AB - Health research has failed to adequately explore the combination of social and
biological sources of differences in men's and women's health. Consequently,
scientific explanations often proceed from reductionist assumptions that
differences are either purely biological or purely social. Such assumptions and
the models that are built on them have consequences for research, health care and
policy. Although biological factors such as genetics, prenatal hormone exposure
and natural hormonal exposure as adults may contribute to differences in men's
and women's health, a wide range of social processes can create, maintain or
exacerbate underlying biological health differences. Researchers, clinicians and
policy makers would understand and address both sex-specific and non-sex-specific
health problems differently if the social as well as biological sources of
differences in men's and women's health were better understood.
PMID- 10190638
TI - Can we stop children and adolescents from smoking?
PMID- 10190639
TI - The relationship between tobacco access and use among adolescents: a four
community study.
AB - The objective of this study was to examine the effectiveness of a longitudinal
community intervention on the reduction of tobacco sales to minors and subsequent
effects on tobacco consumption by youths. The study was conducted in Monterey
County, CA. Four rural communities were randomized into treatment and comparison
arms of the study and middle and high school students in each of these
communities completed surveys assessing knowledge, attitude, and behavior. The
main outcome measures were retail tobacco sales to minors as measured through
store visits (tobacco purchase surveys) and self-reported consumption of tobacco.
Over a three-year period, a diverse array of community interventions were
implemented in the intervention communities. These included community education,
merchant education, and voluntary policy change. In the treatment communities,
the proportion of stores selling tobacco to minors dropped from 75% at baseline
to 0% at the final post-test. In the comparison communities, the proportions were
64% and 39%, respectively. Although the availability of tobacco through
commercial outlets was reduced substantially in intervention communities, youths
reported still being able to obtain tobacco from other sources. Predicted
treatment effects on reported use of tobacco among youths were observed cross
sectionally and longitudinally for younger students (7th graders). The
intervention did not impact tobacco use among older students (9th and 11th
graders) although the trends were in the predicted direction for 9th graders. A
significant intervention effect was found for sex--females in the intervention
communities were less likely to use tobacco post-intervention than females in the
comparison communities. Tobacco sales to minors can be reduced through a broad
based intervention. To prevent or reduce tobacco use by youths, however, multiple
supply-and demand-focused strategies are needed.
PMID- 10190640
TI - Drug policy in China: pharmaceutical distribution in rural areas.
AB - In 1978, China decided to reform its economy and since then has gradually opened
up to the world. The economy has grown rapidly at an average of 9.8% per year
from 1978 to 1994. Medical expenditure, especially for drugs, has grown even more
rapidly. The increase in medical expenditure can be attributed to changing
disease patterns, a higher proportion of older people in the population and fee
for-service incentives for hospitals. Due to the changing economic system and
higher cost of health care, the Chinese government has reformed its health care
system, including its health and drug policy. The drug policy reform has led to
more comprehensive policy elements, including registration, production,
distribution, utilization and administration. As a part of drug policy reform,
the drug distribution network has also been changed, from a centrally controlled
supply system (push system) to a market-oriented demand system (pull system).
Hospitals can now purchase drugs directly from drug companies, factories and
retailers, leading to increased price competition. Patients have easier access to
drugs as more drugs are available on the market. At the same time, this has also
entailed negative effects. The old drug administrative system is not suitable for
the new drug distribution network. It is easy for people to get drugs on the
market and this can lead to overuse and misuse. Marketing factors have influenced
drug distribution so strongly that there is a risk of fake or low quality drugs
being distributed. The government has taken some measures to fight these negative
effects. This paper describes the drug policy reform in China, particularly the
distribution of drugs to health care facilities.
PMID- 10190641
TI - Marital food interaction and dietary behavior.
AB - The objective of this investigation is to consider the role of family food
interaction in healthful dietary activity. A theoretical model is proposed in
which three sets of determinate variables are specified as leading to interaction
in the family on food issues which, in turn, is predicted to have a positive
effect on four indicators of dietary quality. 155 married couples from a
midwestern US state were randomly selected and interviewed. The findings provide
clear evidence of the importance of family food interaction for the quality of
marital partners' diet. Also differences found between husbands and wives
indicate that wives contribute more to husbands' dietary quality than the
reverse, suggesting again the dominant status of wives in family food selection
and preparation.
PMID- 10190642
TI - Prioritising family health needs: a time--space analysis of women's health
related behaviours.
AB - Much has been made over the years of the view that health-related geographical
research has failed fully to explore the complex and mutually reinforcing impact
of social and spatial relations on individual health-related behaviours. At the
same time, there is a growing awareness elsewhere in the social sciences and in
health services research of the generally inadequate exploration of the role of
place particularly at the scale of the local community--in the social
construction of health, illness and health care use. This paper aims to
contribute to the debate by offering a clear framework within which to analyse
the impact of spatially configured social relations at the micro-level. In-depth
interview evidence from Liverpool shows that, looking at the problem from the
perspective of the opportunity-costs of time-space constraints, is a useful means
to understand the distinct ways in which health services are used, when and why,
across different social groups and geographical areas. Particular attention is
drawn to the different thresholds for decision-making depending upon whose health
related needs are being negotiated within the family. The paper concludes with
the latest policy developments in UK primary care which offer professionals the
clear opportunity to develop much more sophisticated understandings of what
constitutes locally-sensitive health service provision. The argument is that such
developments must be based on a firm sense of how individual time-space
circumstances interact with conditions in the local area if the best possible use
of increasingly scarce and valuable resources is to be achieved--particularly in
communities characterised by poverty and social exclusion such as those in
Liverpool.
PMID- 10190643
TI - Effectiveness of community-directed diabetes prevention and control in a rural
Aboriginal population in British Columbia, Canada.
AB - This report presents the process and summative evaluation results from a
community-based diabetes prevention and control project implemented in response
to the increasing prevalence and impact of non-insulin-dependent diabetes
mellitus (NIDDM) in the Canadian Aboriginal population. The 24-month project
targeted the registered Indian population in British Columbia's rural Okanagan
region. A participatory approach was used to plan strategies by which diabetes
could be addressed in ways acceptable and meaningful to the intervention
community. The strategies emphasised a combination of changing behaviours and
changing environments. The project was quasi-experimental. A single intervention
community was matched to two comparison communities. Workers in the intervention
community conducted interviews of individuals with or at risk for diabetes during
a seven-month pre-intervention phase (n = 59). Qualitative analyses were
conducted to yield strategies for intervention. Implementation began in the
eighth month of the project. Trend measurements of diabetes risk factors were
obtained for 'high-risk' cohorts (persons with or at familial risk for NIDDM) (n
= 105). Cohorts were tracked over a 16-month intervention phase, with
measurements at baseline, the midpoint and completion of the study. Cross
sectional population surveys of diabetes risk factors were conducted at baseline
and the end of the intervention phase (n = 295). Surveys of community systems
were conducted three times. The project yielded few changes in quantifiable
outcomes. Activation of the intervention community was insufficient to enable
individual and collective change through dissemination of quality interventions
for diabetes prevention and control. Theory and previous research were not
sufficiently integrated with information from pre-intervention interviews.
Interacting with these limitations were the short planning and intervention
phases, just 8 and 16 months, respectively. The level of penetration of the
interventions mounted was too limited to be effective. Attention to process is
warranted and to the feasibility of achieving effects within 24 months.
PMID- 10190644
TI - Addressing birth in Gaza: using qualitative methods to improve vital
registration.
AB - The use of anthropological qualitative methods to validate and improve health
surveillance data is demonstrated through an examination of the process of birth
registration in Gaza. Theoretically, the importance of understanding the link
between historical events and microlevel decision-making is emphasized both in
general terms and specifically in the context of the Gaza Strip today. In the
course of interviewing a sample of mother/infant pairs selected from a register
of births in the Gaza Strip it became evident that 100% of the addresses were
incomplete. Using qualitative methods in the form of field visits and interviews
with physicians, clerks and nurses, an understanding of the information pathway
for birth registration data was developed. It was also established that there was
some erroneous recording of birthweight. An intervention was designed which
failed to improve the accuracy of addresses but did improve the recording of
birthweight.
PMID- 10190645
TI - Improving drug use: a case study of events which led to changes in use of
flucloxacillin in Australia.
AB - Policy makers and health professionals charged with implementing policies to
improve medication use require knowledge as to how to integrate and co-ordinate
strategies and interventions which have been shown to be effective. Experimental
methodologies are commonly used to assess the effectiveness of interventions to
improve medication use and while valuable for determining the effectiveness of
particular interventions, they do not add to our understanding of how to co
ordinate and integrate multiple initiatives to improve medication use. We argue
that analyses of the overall system of events which are implemented to improve
medication use are also needed. In this paper, we demonstrate how the case study
analysed within the framework of the Transtheoretical Model of behaviour change
can be used to provide an understanding of the relationship of events which
result in changes in medication use. A case study of the sequence of events which
led to changes in the utilisation of flucloxacillin in Australia is assessed. The
analysis demonstrated that the effectiveness of individual interventions was
dependent upon the initiatives which were implemented concurrently and those that
had been implemented previously. Changes in the utilisation of flucloxacillin
resulted from regulatory interventions and the promotion of appropriate
alternative therapies. The effectiveness of this change was enhanced by previous
interventions which had raised awareness amongst health professionals of the
adverse hepatic reaction associated with the use of flucloxacillin. This
methodology adds to those currently employed to study methods of improving use of
medications. It provides an understanding of the role of each initiative in the
overall system. This is valuable for policy makers, providing them with
information on how to co-ordinate and orchestrate the myriad of activities which
support quality use of medicines.
PMID- 10190646
TI - Regression of left ventricular hypertrophy; what are appropriate therapeutic
objectives?
PMID- 10190647
TI - Therapeutic drug monitoring of antimetabolic cytotoxic drugs.
AB - Therapeutic drug monitoring is not routinely used for cytotoxic agents. There are
several reasons, but one major drawback is the lack of established therapeutic
concentration ranges. Combination chemotherapy makes the establishment of
therapeutic ranges for individual drugs difficult, the concentration-effect
relationship for a single drug may not be the same as that when the drug is used
in a drug combination. Pharmacokinetic optimization protocols for many classes of
cytotoxic compounds exist in specialized centres, and some of these protocols are
now part of large multicentre trials. Nonetheless, methotrexate is the only agent
which is routinely monitored in most treatment centres. An additional factor,
especially in antimetabolite therapy, is the existence of pharmacogenetic enzymes
which play a major role in drug metabolism. Monitoring of therapy could include
assay of phenotypic enzyme activities or genotype in addition to, or instead of,
the more traditional measurement of parent drug or drug metabolites. The
cytotoxic activities of mercaptopurine and fluorouracil are regulated by
thiopurine methyltransferase (TPMT) and dihydropyrimidine dehydrogenase (DPD),
respectively. Lack of TPMT functional activity produces life-threatening
mercaptopurine myelotoxicity. Very low DPD activity reduces fluorouracil
breakdown producing severe cytotoxicity. These pharmacogenetic enzymes can
influence the bioavailability, pharmacokinetics, toxicity and efficacy of their
substrate drugs.
PMID- 10190649
TI - Pharmacokinetics of tolbutamide in ethnic Chinese.
AB - AIMS: Ethnic differences in drug disposition have been described for many drugs.
Despite the widespread use of tolbutamide in Asian populations, the
pharmacokinetics of tolbutamide, a CYP2C9 substrate, have not been described in
ethnic Chinese. METHODS: The pharmacokinetics of tolbutamide (500 mg orally) were
studied in 10 young, healthy volunteers (seven male/three female; age 21-29
years), each of whom had four ethnic Chinese grandparents. Plasma concentrations
of tolbutamide were measured for 32 h post-dose by high performance liquid
chromatography. The concentrations of hydroxytolbutamide and carboxytolbutamide
were also measured in urine for 32 h post-dose. Noncompartmental pharmacokinetic
parameters were calculated using standard equations and compared with those
previously reported in Caucasian subjects using the Mann-Whitney U test. RESULTS:
Pharmacokinetic parameters in Chinese (mean+/-s.d.) including Cmax (63+/-11
microg ml(-1)), tmax (median 3.3 h; range 1.6-6.0 h), V/F (9.1+/-1.7 l) and t1/2,
(9.1 h; harmonic mean) were similar to the values in Caucasians. CL/F (637+/-88
ml h(-1)) was higher in Chinese than Caucasians. The urinary recoveries of
hydroxytolbutamide (13+/-1% of dose) and carboxytolbutamide (68+/-5% of dose) and
the partial apparent metabolic clearance (0.15+/-0.02 ml min(-1) kg(-1)) in
Chinese were comparable with Caucasians. CONCLUSIONS: The pharmacokinetics of
tolbutamide have been described in ethnic Chinese and the disposition is similar
to that reported in Caucasians. This study suggests that there is no substantial
ethnic difference in the tolbutamide hydroxylase activity of CYP2C9.
PMID- 10190648
TI - Tolterodine does not affect the human in vivo metabolism of the probe drugs
caffeine, debrisoquine and omeprazole.
AB - AIM: To investigate the in vivo effect of treatment with tolterodine on
debrisoquine 4-hydroxylation (an index of CYP2D6 activity), omeprazole 5
hydroxylation (CYP2C19), omeprazole sulphoxidation (CYP3A4) and caffeine N3
demethylation (CYP1A2). METHODS: Twelve healthy male volunteers (eight extensive
metabolisers [EMs] and four poor metabolisers [PMs] with respect to CYP2D6)
received 4 mg tolterodine L-tartrate orally twice daily for 6 days. All subjects
were EMs with respect to CYP2C19. The subjects received single oral doses of
debrisoquine (10 mg), omeprazole (20 mg) and caffeine (100 mg) for determination
of the appropriate metabolic ratios (MR). The drugs were given on separate
consecutive days, before, during and after the co-administration of tolterodine.
RESULTS: Mean serum tolterodine concentrations were 5-10 times higher in PMs than
in EMs. Serum concentrations of the active 5-hydroxymethyl metabolite of
tolterodine, 5-HM, were not quantifiable in PMs. The mean MR of debrisoquine (95%
confidence interval) during tolterodine treatment was 0.50 (0.25-0.99) and did
not differ statistically from the values before [0.49 (0.20-1.2)] and after
tolterodine administration [0.46 (0.14-1.6)] in EMs. The mean MR of omeprazole
hydroxylation and sulphoxidation or caffeine metabolism were not changed in the
presence of tolterodine in either EMs or PMs. Debrisoquine and caffeine had no
significant effect on the AUC(1,3 h) of either tolterodine or 5-HM, but during
omeprazole administration small decreases (13-19%) in these parameters were seen.
CONCLUSIONS: Tolterodine, administered at twice the expected therapeutic dosage,
did not change the disposition of the probe drugs debrisoquine, omeprazole and
caffeine and thus had no detectable effect on the activities of CYPs 2D6, 2C19,
3A4 and 1A2. Alteration of the metabolism of substrates of these enzymes by
tolterodine is unlikely to occur.
PMID- 10190650
TI - Evaluation of the effect on heart rate variability of a beta2-adrenoceptor
agonist and antagonist using non-linear scatterplot and sequence methods.
AB - AIMS: To examine the impact on heart rate variability (HRV), of agonism or
antagonism at the cardiac beta2-adrenoceptor in healthy volunteers, using
standard time-domain summary statistics and non-linear methods (scatterplot and
quadrant analysis). METHODS: Under double-blind and randomised conditions (Latin
square design), 17 normal volunteers received placebo, salbutamol (beta2
adrenoceptor partial agonist), ICI 118,551 (specific beta2-adrenoceptor
antagonist), or salbutamol plus ICI 118,551. Single oral doses of medication (at
weekly intervals) were administered at 22.30 h, with HRV assessed from the
sleeping heart rates. RESULTS: Salbutamol reduced the long-term (SDNN: 135 ms
[120, 156], SDANN: 107 ms [89, 124]) time-domain indicators of HRV compared with
placebo (SDNN: 39 [24, 55], SDANN 42 [29, 56], [mean difference [95% confidence
intervals of difference]]). Alone, ICI 118,551 did not effect HRV, but in
combination blocked the actions of salbutamol. Scatterplot length (944 ms [869,
1019]) and area (222*10(3) ms2 [191, 253]) were reduced by salbutamol compared
with placebo; (length difference (164 [98, 230]) and area difference 59 [36,
83]). Scatterplot width (dispersion) was lower at both low (width RR-1 25%
salbutamol 277 ms [261, 293]: salbutamol minus placebo 14 ms [0, 28]) and high
(width 75% salbutamol 417 [391, 443]: salbutamol minus placebo 41 [20, 62]) heart
rates. ICI 118,551 alone did not alter scatterplot parameters but in combination
blocked the effect of salbutamol. Cardiac acceleration episodes (i.e. consecutive
deltaRR and deltaRRn+1 shorten) were increased following salbutamol 7288 [6089,
8486] compared with placebo -1890 [-2600, -1179]; the beat-to beat difference
(deltaRRn+1) was reduced after salbutamol compared with the other treatments. ICI
118,551 did not effect acceleration episodes but reduced the effect of salbutamol
when used in combination. CONCLUSIONS: Agonism at the cardiac beta2-adrenoceptor
in healthy volunteers with salbutamol altered autonomic balance towards
sympathetic dominance; this re-balancing was blocked by ICI 118,551 given in
combination with salbutamol. However antagonism at the beta2-adrenoceptor with
ICI 118,551 alone did not significantly alter the HRV. The beta2-adrenoceptor
modulates HRV in healthy volunteers; the implications of agonism and antagonism
at the beta2-adrenoceptor in cardiovascular disease states warrants further
investigation.
PMID- 10190651
TI - Platelet alpha2-adrenoceptor alterations in patients with essential hypertension.
AB - AIMS: The purpose of this study was to determine whether human platelet alpha2
adrenoceptors were altered in essential hypertension. A systematic analysis was
carried out on 165 normotensives and 124 untreated primary hypertensives.
METHODS: The study was performed at different levels: i) density and affinity of
platelet alpha2-adrenoceptors were determined by receptor binding assays using
the full alpha2-adrenoceptor agonist [3H]-UK 14304 and a thermodynamic analysis
of data was carried out to evaluate if binding mechanisms at the molecular level
were altered during hypertension; ii) the functionality of Gi proteins coupled to
alpha2-adrenoceptors and iii) forskolin-stimulated cAMP levels were measured.
RESULTS: Platelet alpha2-adrenoceptors mean density (Bmax) and affinity (Kd) (+/
s.e.mean) were significantly lower and higher, respectively, in normotensive than
in hypertensive subjects [Bmax=327+/-4 vs 435+/-5 fmol mg(-1) of protein (P<0.01)
and Kd=3.76+/-10.05 vs 6.50+/-0.15 nM (P<0.01), respectively]. The 50%
stimulating concentration of adrenaline on [35S]-GTPgammaS binding to Gi proteins
was significantly (P<0.01) lower in normotensives (12+/-2 nM) than in
hypertensives (110+/-10 nM). The 50% inhibiting concentration of adrenaline on
forskolin-stimulated cAMP levels was significantly (P<0.01) lower in normotensive
(22+/-2 nM) than in hypertensive subjects (200+/-25 nM). CONCLUSIONS: Present
analysis, including receptorial and functional data, provides evidence that
marked alterations occur in platelet alpha2-adrenoceptors of hypertensive
subjects.
PMID- 10190652
TI - Contribution of nitric oxide to beta2-adrenoceptor mediated vasodilatation in
human forearm arterial vasculature.
AB - AIMS: beta2-adrenoceptor agonists are generally considered to produce endothelium
independent vasodilatation through adenylate cyclase. We determined whether
nitric oxide contributes to beta2-adrenoceptor vasodilatation in human arterial
vasculature. METHODS: Forearm blood flow responses to brachial intra-arterial
infusions of ritodrine (2.5-50 microg min(-1)), a selective beta2-adrenoceptor
agonist, were determined in 24 healthy, normotensive subjects (mean age 22 years,
5F) on two occasions with initial and concomitant administration of L-NMMA (800
microg min(-1)), an NO synthase inhibitor, or noradrenaline (5-30 ng min(-1)), a
control constrictor not affecting basal NO activity. Responses to the endothelium
dependent vasodilator scrotonin (n = 6) and an endothelium independent
vasodilator GTN (n = 9) were also determined. RESULTS: Maximal dilatation to
ritodrine during L-NMMA infusion (310+/-32%; mean+/-s.e.mean) was reduced
compared to that during noradrenaline infusion (417+/-41%, P<0.05), as were
summary responses (1023+/-101 vs 1415+/-130; P<0.05). Responses to GTN were
unaffected by L-NMMA compared to noradrenaline; max 177+/-26 vs 169+/-20%, 95% CI
for difference -33,48; P=0.68; summary response 361+/-51 vs 396+/-37, 95% CI
142,71; P=0.46. Dilator responses to serotonin were reduced by L-NMMA; max 64+/
20 vs 163+/-26%, P<0.01; summary response 129+/-36 vs 293+/-60; P<0.05) and to a
greater extent than ritodrine (58+/-7 vs 25+/-14%, P<0.05). CONCLUSIONS: beta2
adrenoceptor mediated vasodilatation in the human forearm has an NO mediated
component. The underlying mechanism for this effect is unclear, but flow mediated
vasodilatation is unlikely to be responsible.
PMID- 10190653
TI - Fosinopril reduces left ventricular mass in untreated hypertensive patients: a
controlled trial.
AB - AIMS: Left ventricular hypertrophy is a powerful predictor of cardiovascular
morbidity and mortality. We tested the hypothesis that fosinopril, an angiotensin
converting enzyme inhibitor, reduces left ventricular mass in hypertensive
patients. METHODS: Thirty-three patients with untreated mild essential
hypertension were randomised to treatment with oral fosinopril (10 mg-20 mg
daily) or placebo for 12 weeks. The primary outcome measure was the change in
left ventricular mass index determined by echocardiography. RESULTS: Diastolic
blood pressure changed from 95.5+/-2.1 mmHg at baseline to 96.6+/-2.8 mmHg at the
final visit in control patients and changed from 96.6+/-2.3 mmHg to 91.5+/-3.0
mmHg in patients treated with fosinopril (P= 0.04). Systolic blood pressure
changed from 147.4+/-3.2 mmHg at baseline to 152.7+/-4.4 mmHg at the final visit
in control patients and changed from 157.6+/-5.1 mmHg to 149.1+/-6.1 mmHg in
patients treated with fosinopril (P=0.02). Fosinopril reduced diastolic pressure
by 6.3 (95%CI 0.3-12.4) mmHg and systolic pressure by 13.3 (95%CI 2.7-23.8) mmHg
compared with placebo. The left ventricular mass index changed from 110.0+/-8.3
gm(-2) to 113.1+/-8.7 g m(-2) in the control patients and changed from 120.8+/
5.8 g m(-2) to 109.0+/-7.5 g m(-2) in patients treated with fosinopril (P=0.02).
Fosinopril reduced left ventricular mass index by 14.9 (95%CI 2.2-27.6) g m(-2)
compared with placebo. There was no significant change in the left ventricular
systolic or diastolic function, nor were there any significant changes in plasma
electrolytes and renal function. CONCLUSIONS: Treatment with fosinopril for 12
weeks reduced left ventricular mass significantly in hypertensive patients.
PMID- 10190654
TI - The haemodynamic effect of the 5HT1 agonist BMS-180048: a class effect of
triptans?
AB - AIMS: To investigate the effects of an intravenous infusion of BMS-180048, a
novel 5HT1-like agonist, on the systemic, pulmonary and coronary circulations in
patients undergoing diagnostic cardiac catheterisation. METHODS: Ten patients
(mean age 55 years (range 41-65)) were studied during diagnostic cardiac
catheterisation. The haemodynamic response to an intravenous (i.v.) infusion for
30 min of BMS-180048 (0.56 mg kg(-1) h(-1) for 10 min and 0.39 mg kg(-1) h(-1)
for 20 min) was assessed via a 7F Swan Ganz catheter and thermodilution cardiac
output system. Quantitative coronary angiography was performed at 10 min
intervals. RESULTS: BMS-180048 caused a significant increase in systemic arterial
systolic blood pressure (rise of 32.5 mmHg, 95% CI 24,44.5) P=0.009), pulmonary
artery systolic (12.2 mmHg, 95% CI 6.8,18.5; P=0.009) and diastolic pressures
(8.5 mmHg, 95% CI 5.0,13.8; P=0.009), right atrial pressure (4 mmHg, 95% CI
1.5,5.2; P=0.013) and pulmonary capillary wedge pressure (9.5 mmHg 95% CI
5.2,14.0; P=0.09). There was no significant change in cardiac output (0.1 l min(
1), 95% CI -0.17,0.57, P>0.05). Mean coronary artery diameter in the proximal
coronary segments decreased by 0.73 mm (95% CI -1.22,-0.15; P=0.03) at 35 min.
The corresponding reduction in middle segments was 0.26 mm (95% CI -0.395,-0.08;
P=0.02). There was a non-significant trend to constriction in the most distal
segments of 0.28 mm (95% CI -0.68,0.015); P=0.06). One patient experienced chest
pain with ECG changes suggestive of ischaemia. CONCLUSIONS: BMS-180048 displayed
a cardiovascular profile similar to that previously reported for sumatriptan.
These changes appear to reflect a class effect of these agents.
PMID- 10190655
TI - The effects of vapreotide, a somatostatin analogue, on gastric acidity,
gallbladder emptying and hormone release after 1 week of continuous subcutaneous
infusion in normal subjects.
AB - AIMS: Somatostatin analogues (e.g. vapreotide) are used for treatment of
acromegaly, endocrine tumours and variceal bleeding. The pharmacodynamic effects
of vapreotide have, however, not been documented in the gastrointestinal tract.
The aim of this study was to investigate the effects of continuous vapreotide
administration on gastric acidity, gallbladder contraction and hormone release.
METHODS: Ten healthy males participated in this randomised, placebo-controlled,
double-blind, crossover trial. A constant vapreotide (or placebo) infusion (1.5
mg day(-1) s.c.) was given for 7 days with a portable pump. Intragastric pH was
monitored on days 2 and 7. Gallbladder volume was sonographically assessed and
the maximal ejection fraction was calculated. In addition basal and postprandial
plasma levels of gastrin and cholecystokinin (CCK) were measured. RESULTS: After
an initial increase in the median 24 h intragastric pH to a value of 2.6 on day
2, vapreotide's effect on pH decreased: (day 7: median pH=1.9; respective placebo
values were 1.7 and 1.5). On the same days with vapreotide treatment, gallbladder
contraction and plasma levels of CCK were reduced; maximal ejection fractions
after meal stimulation were 18% and 20% (respective placebo values were 57% and
62%). Plasma gastrin levels were not changed with vapreotide treatment.
CONCLUSIONS: The short lasting effect of vapreotide on intragastric acidity
suggests a down-regulation of somatostatin receptors during treatment. The lack
of effect on gastrin indicates that the effects on gastric pH are not mediated by
gastrin. Constant vapreotide infusion (but not placebo) reduced gallbladder
contraction suggesting a long-lasting effect on biliary function.
PMID- 10190658
TI - The effect of steady-state ropinirole on plasma concentrations of digoxin in
patients with Parkinson's disease.
AB - AIMS: The aim of this single-blind study was to assess the effect of ropinirole,
a novel treatment for Parkinson's disease, on the steady-state pharmacokinetics
and safety of digoxin in 10 patients with Parkinson's disease. METHODS: There
were three parts to the study: digoxin once daily plus placebo three times daily
for 1 week; digoxin once daily plus ropinirole three times daily for 6 weeks; and
digoxin once daily plus placebo three times daily for 1 week. Serial blood
samples were collected over 24 h at the end of each part of the study for
pharmacokinetic assessment. Pre-dose blood samples were collected on specific
days throughout the study to assess the attainment of steady-state plasma levels
of digoxin. The primary endpoints were AUC(0, tau) and Cmax for digoxin. RESULTS:
There was a mean decrease of 10% in digoxin AUC (0, tau) (90% CI: 0.79, 1.01) and
a 25% decrease in digoxin Cmax (90% CI: 0.58, 0.97) when ropinirole was co
administered, compared with digoxin alone Cmin plasma values for digoxin,
however, were fairly constant throughout the study (point estimates 0.99, 95% CI:
0.85, 1.15). Changes in trough levels of digoxin are believed to be the most
reliable way of assessing steady-state concentrations of digoxin, and therefore
the clinical significance of an interaction. Changes in Cmax are too readily
influenced by other factors. CONCLUSIONS: These results therefore indicate that
on pharmacokinetic grounds no dose adjustment is necessary for digoxin co
administered with ropinirole.
PMID- 10190657
TI - Incidence and risk factors for hyponatraemia following treatment with fluoxetine
or paroxetine in elderly people.
AB - AIMS: To establish the incidence, time course and risk factors of hyponatraemia
complicating treatment with fluoxetine or paroxetine in an elderly population.
METHODS: Retrospective descriptive and case control study in an
inpatient/outpatient assessment and rehabilitation service for people aged 65
years and over. Fourteen elderly patients with hyponatraemia complicating
treatment with fluoxetine or paroxetine, matched with 56 controls drawn from 845
patients treated with fluoxetine or paroxetine over 3.5 years. No other SSRI
antidepressants were used over the study period. RESULTS: The incidence of
hyponatraemia was 4.7/1000 people treated/year (6.3/1000 for fluoxetine and
3.5/1000 for paroxetine). Hyponatraemia was detected at a median 13.5 (mean 18.6,
range 4-64) days after commencing the drug. Mean (95% confidence intervals) body
weights were lower in cases at 53.0 (95% CI 46.5-59.5) kg compared with controls
at 64.5 (95% CI 60.1-68.4) kg (P<0.01). 71% of cases were women compared with 45%
of controls (P=0.07) but the effect of gender was confounded by body weight.
There were trends for cases to be older (odds ratio 1.10: 95% CI 0.99, 1.23) and
lighter (odds ratio 0.92, 95% CI 0.86, 0.99). CONCLUSIONS: Approximately 1 in 200
elderly people treated per year with fluoxetine or paroxetine developed
complicating hyponatraemia. Low body weight was a particular risk factor. Most
cases occurred within 3 weeks of treatment.
PMID- 10190656
TI - Glomerular, tubular and interstitial nephritis associated with non-steroidal
antiinflammatory drugs. Evidence of a common mechanism.
AB - AIMS: To study the mechanisms behind NSAID-associated nephropathy. METHODS:
Analysis of published case reports satisfying strict criteria for NSAID
nephropathy. RESULTS: Ninety-seven cases with acute nephritis (AN; 19 patients),
minimal change nephropathy (MC; 38 patients), membranous glomerulonephritis (MGN;
19 patients), focal sclerosis (FS; 13 patients) and other glomerulonephritis
subgroups (8 patients) were identified. Hypersensitivity reactions were seen in
all groups, most often in AN. Proteinuria was more severe in MC and FS than in
MGN and unrelated to amount of glomerular deposits. The mean NSAID treatment time
was 1.7 months in AN, 8.2 months in MC and 39 months in MGN and associated with
amount of glomerular deposits, fusion of podocytes and proteinuria, and inversely
associated with hypersensitivity, interstitial damage and renal failure.
Rheumatic diseases were common in MGN. At follow-up 68 of 72 patients who had
discontinued NSAID treatment had improved, 57 with normal renal function.
CONCLUSIONS: NSAID nephropathy may be caused by hypersensitivity. The reaction is
milder than in drug-induced acute tubulointerstitial nephritis, probably because
the offending drug inhibits the inflammatory reaction it has started itself.
Heavy proteinuria is probably due to lymphokines produced as a result of the
immunological response. If the allergic reaction is strong, AN is produced
rapidly with severe renal failure but little proteinuria; if it is less violent,
immunocompetent cells may develop to produce lymphokines and proteinuria. Immune
complexes may be formed eventually, secondary to the increased glomerular
permeability, more easily in patients with a hyperactive immune system and with
little consequence for renal function.
PMID- 10190659
TI - Effects of ketoconazole on the erythromycin breath test and the dapsone recovery
ratio.
PMID- 10190660
TI - Potentiation of acenocoumarol during vaginal administration of miconazole.
PMID- 10190661
TI - Visual hallucinations due to radiocontrast media. Report of two cases and review
of the literature.
PMID- 10190662
TI - Adverse effects of herbal remedies and OTC medicines.
PMID- 10190663
TI - Providing patients with written information helps them to be aware of and report
adverse drug reactions?
PMID- 10190664
TI - FIGO staging of gynecologic cancer. 1994-1997 FIGO Committee on Gynecologic
Oncology. International Federation of Gynecology and Obstetrics.
PMID- 10190665
TI - Iatrogenic multiple birth, multiple pregnancy and assisted reproductive
technologies.
PMID- 10190666
TI - Pre-eclampsia associated with increased lipid peroxidation and decreased serum
vitamin E levels.
AB - OBJECTIVE: To evaluate lipid peroxidation and the serum levels of the antioxidant
vitamin E in pre-eclampsia according to the disease severity. METHOD: Serum
malondialdehyde (MDA) and vitamin E levels were measured in 18 pre-eclamptic, 15
eclamptic and 25 normotensive pregnant women in Ondokuz Mayis University
Hospital. The correlation of these levels with the factors indicating disease
severity was tested. Mann-Whitney U-test and correlation coefficients were used
for the statistical analysis. RESULT: Both the pre-eclamptic and the eclamptic
patients had higher MDA and lower vitamin E levels compared with control (P <
0.05); but these values were not significantly different from each other (P >
0.05). MDA levels were significantly correlated with the systolic and diastolic
blood pressure (BP) and with serum uric acid levels. There was significant but
negative correlation with the vitamin E levels. CONCLUSION: There is an imbalance
between lipid peroxidation and serum vitamin E levels in pre-eclampsia and
eclampsia. Increased lipid peroxidation is well correlated with the increase in
systolic and diastolic BP measurements and serum uric acid levels.
PMID- 10190667
TI - Extra-amniotic saline infusion versus extra-amniotic prostaglandin F2alpha for
cervical ripening and induction of labor.
AB - OBJECTIVE: To compare the effectiveness of extra-amniotic saline infusion versus
extra-amniotic prostaglandin F2alpha for cervical ripening, induction of labor
and achievement of vaginal delivery in patients with unfavorable cervices.
METHOD: A randomized trial of extra-amniotic saline infusion versus extra
amniotic prostaglandin F2alpha performed at Harare Central Hospital Maternity
Unit, Zimbabwe. One hundred and sixty-four patients were recruited from those
referred to Harare Central Hospital Maternity Unit who required induction of
labor for either maternal or fetal indications. RESULTS: 162 patients (extra
amniotic PgF2alpha group, N = 81; extra-amniotic saline infusion group, N = 81)
had complete information. Two patients (one from each group) were lost to follow
up. The demographic characteristics of the patients and the indications for
induction were not statistically different. There was a marginally statistically
significant difference in the change of Bishop Score in favor of the extra
amniotic saline infusion (4.0, S.D. = 1.4) as compared to (4.5, S.D. = 1.5) for
extra-amniotic PgF2alpha (P value = 0.047). All other parameters showed no
statistically significant differences. Maternal and fetal complications were
minimal and not significantly different. Extra-amniotic saline infusion was
however almost six times cheaper than PgF2alpha. CONCLUSION: Extra-amniotic
saline infusion is as effective as PgF2alpha, safe, but much cheaper than
PgF2alpha and should be seriously considered as a method of first choice in
resource-poor settings.
PMID- 10190668
TI - Does the station of the fetal head during epidural analgesia affect labor and
delivery?
AB - OBJECTIVE: To assess whether the station of the fetal head when lumbar epidural
analgesia is administered influences the duration or the mode of delivery in low
risk laboring women. METHODS: We prospectively evaluated 131 consecutive cases of
low-risk parturients at term who requested intrapartum epidural analgesia.
Obstetric outcome of 65 parturients who underwent epidural analgesia when the
fetal head was low in the birth canal was compared to 66 patients whose fetal
head station was above the ischial spine. RESULTS: Both groups were similar in
their obstetric characteristics. Cervical dilatation when performing the epidural
analgesia was similar in both groups. The duration of labor and mode of delivery,
as well as percentage of malpositions, were not significantly different in the
two groups. CONCLUSIONS: The station of the fetal head while initiating epidural
analgesia does not influence the duration of labor or the mode of delivery.
Therefore, there is no justification to delay epidural analgesia in labor until
the presenting fetal part is engaged.
PMID- 10190670
TI - Prior third- or fourth-degree perineal tears and recurrence risks.
AB - OBJECTIVE: The objective of the present study is to determine the recurrence risk
of a third-degree (into the anal sphincter) or a fourth-degree (into the rectum)
perineal tear in women with a prior extensive laceration. METHODS: Data were
gathered from our computerized perinatal database between January 1990 and
December 1994. Women who had two consecutive singleton deliveries were chosen as
subjects. RESULTS: The rate of an extensive perineal laceration was greater if a
tear had occurred in a previous pregnancy (19 of 178 cases, 10.7% vs. 56% of 1563
cases, 3.6%, odds ratio 3.4. A 95% confidence interval: 1.8-6.4; p < 0.0001). A
prior tear remained a risk factor after controlling for other variables (epidural
analgesia, episiotomy, oxytocin use, operative vaginal delivery, fetal
macrosomia). CONCLUSION: A prior third-degree or fourth-degree perineal tear is
associated with a 3.4-fold increased risk of a recurrent severe obstetrical
laceration.
PMID- 10190669
TI - Intracervical misoprostol as an effective method of labor induction at term.
AB - OBJECTS: The purpose of this study was to evaluate the safety and effectiveness
of intracervical misoprostol for the induction of labor at term. METHODS: Eighty
nine term pregnancies requiring induction of labor were treated intracervically
with 50 microg of misoprostol. The dose was repeated every 4 h until adequate
uterine contraction and cervical dilatation were achieved. Status of cervical
ripening, uterine contraction, cervical dilatation, labor course and side effects
were recorded and analyzed. RESULTS: Among the 89 patients, 58 had an unfavorable
cervix (Bishop score < or = 4) and 31 had a favorable cervix (Bishop score > 4).
Labor was successfully induced in all cases, most (93.3%) of which required a
single dose of misoprostol. Seventy-two patients (81%) proceeded to spontaneous
vaginal delivery, and 61 (85%) deliveries were achieved within 12 h. The other 17
cases received cesarean delivery with indications of fetopelvic disproportion
(six cases), failure of induction (seven cases) and acute fetal distress (four
cases). The mean duration from induction to regular uterine contraction and to
delivery was 483+/-537 min and 79.2+/-38.2 min, respectively, with no significant
difference between the two groups with differing status of cervical ripening.
Complications of uterine contraction, including tachysystole (15 cases),
hypertonus (one case) and hyperstimulation (10 cases) were more common in the
group of unfavorable cervix (45%) than that of favorable cervix (23%) (P < 0.05).
CONCLUSION: In addition to the oral and intravaginal routes of administration,
intracervical misoprostol at a single dose of 50 microg appears to be an
effective method for induction of labor at term, but caution should be taken with
cases with unfavorable cervix.
PMID- 10190671
TI - Estrogen replacement therapy in breast cancer survivors.
AB - OBJECTIVE: To determine whether estrogen replacement therapy (ERT) adversely
affected outcome of breast cancer survivors. METHOD: A prospective descriptive
study of all breast cancer survivors who requested ERT because of intractable
menopausal symptoms. All patients presented voluntarily as gynecological
outpatients and were all given oral continuous opposed ERT: 20 premarin and
medroxyprogesterone and four tibolone. RESULTS: Twenty-four patients who had
previously been treated for breast cancer 8-91 months prior to their initiating
ERT have been observed for 24-44 months. There were 15 patients with stage 1,
eight with stage 2 and one with stage 4 breast cancer. The mean age of the
patients at commencement of ERT was 48 years (range 42-61). Two patients had a
biopsy of a suspicious breast nodule: both of which were benign. There have not
been any recurrences to date. CONCLUSION: Breast cancer survivors did not have
their outcome adversely affected by ERT during an observation period of 24-44
months.
PMID- 10190672
TI - The Abha septuplets: prepregnancy, pregnancy, and outcome.
PMID- 10190673
TI - Acute myocardial infarction associated with postpartum ergot alkaloid
administration.
PMID- 10190674
TI - Effect of the Cu T380 IUD on hemoglobin and iron stores in Egyptian women.
PMID- 10190675
TI - Skin reactions to transdermal estrogen replacement therapy in a tropical climate.
PMID- 10190676
TI - Severe hyperthermia following use of vaginal misoprostol for pre-operative
cervical priming.
PMID- 10190677
TI - Pyometra complicating cancer of the cervix.
PMID- 10190678
TI - Hysteroscopic treatment of unicornuate uterus associated with a cavitary
rudimentary horn.
PMID- 10190679
TI - Replacement therapy in postmenopausal women and breast cancer risk.
PMID- 10190680
TI - Ethics, justice and women's health.
PMID- 10190681
TI - ACOG educational bulletin. Obstetric aspects of trauma management. Number 251,
September 1998 (replaces Number 151, January 1991, and Number 161, November
1991). American College of Obstetricians and Gynecologists.
PMID- 10190682
TI - ACOG committee opinion. Liability implications of recording procedures or
treatments. Number 207, September 1998. Committee on Professional Liability.
American College of Obstetricians and Gynecologists.
PMID- 10190683
TI - ACOG committee opinion. Delivery by vacuum extraction. Number 208, September
1998. Committee on Obstetric Practice. American College of Obstetricians and
Gynecologists.
PMID- 10190684
TI - Chemokine regulation of inflammatory-mediated nervous system diseases.
PMID- 10190685
TI - Chemokines and chemokine receptors in CNS pathology.
PMID- 10190686
TI - Chemokine and chemokine receptor expression in the central nervous system.
AB - A decade ago several new cytokines were described that orchestrated the
activation and migration of immune cells. These newly described cytokines, of
which interleukin-8 (IL-8) was a representative member, defined a novel group of
molecules called chemokines (chemotactic cytokines). Chemokines are low molecular
weight, 8-12 kDa, basic proteins that have been classified into four distinct
families, CXC, CC, C and CX3C, based on the position of their first two conserved
cysteine residues. The expression and biological function of chemokines along
with their cognate receptors have been well described on various subsets of
leukocytes. Only more recently have these molecules been described on various
cells within the central nervous system. These pro-inflammatory proteins have
been implicated in a variety of diseases within the central nervous system from
Multiple Sclerosis to AIDS dementia. While chemokines are likely to enhance the
evolution of central nervous system inflammatory disorders they also have other
roles in normal brain function and development. This review summarizes the role
of chemokines and their receptors in the normal and pathophysiological brain.
PMID- 10190687
TI - Chemokines and peripheral nerve demyelination.
AB - It has been speculated that beta-chemokines play a pivotal role in the
development of peripheral nervous system (PNS) disorders characterized by
mononuclear cell infiltration. In experimental allergic neuritis (EAN), an animal
model for human Guillain-Barre syndrome (GBS) with mononuclear cell infiltration,
we found by quantitative PCR that beta-chemokine messages were upregulated during
the active stage. Moreover, an increase in the monocyte chemoattractant protein-1
(MCP-1) message was found in the preclinical stage of EAN, suggesting the
critical role of MCP-1 for inducing mononuclear cell infiltrations in this model.
Since many cell lineages other than immune cells can produce chemokines, this
early upregulation of MCP-1 may be mediated by non-immune cells, probably
endothelia or Schwann cells. To date, apart from MCP-1, only RANTES (Regulated on
activation, normal T cell expressed and secreted) and macrophage inflammatory
protein (MIP)-1alpha have been examined in EAN and found to have similar kinetics
of induction. Therefore, understanding the regulation of production of these
chemokines as well as mechanisms of inhibiting chemokine/receptor interactions in
the PNS may ultimately lead to disease-specific therapy for GBS and related
demyelinating disorders.
PMID- 10190688
TI - Chemokines/chemokine receptors in the central nervous system and Alzheimer's
disease.
AB - Alzheimer's disease (AD) is the most common cause of dementia in the elderly, and
the fourth leading cause of death in the United States. Its pathological changes
include amyloid beta deposits, neurofibrillary tangles and a variety of
'inflammatory' phenomenon such as activation of microglia and astrocytes. The
pathological significance of inflammatory responses elicited by resident central
nervous system (CNS) cells has drawn considerable attention in recent years.
Chemokines belongs to a rapidly expanding family of cytokines, the primary
function of which is control of the correct positioning of cells in tissues and
recruitment of leukocytes to the site of inflammation. Study of this very
important class of inflammatory cytokines may greatly help our understanding of
inflammation in the progress of AD, as well as other neurodegenerative diseases.
So far, immunoreactivity for a number of chemokines (including IL-8, IP-10, MIP
1beta, MIPalpha and MCP-1) and chemokine receptors (including CXCR2, CXCR3,
CXCR4, CCR3, CCR5 and Duffy antigen) have been demonstrated in resident cells of
the CNS, and upregulation of some of the chemokines and receptors are found
associated with AD pathological changes. In this review, we summarize findings
regarding the expression of chemokines and their receptors by CNS cells under
physiological and pathological conditions. Although little is known about the
potential pathophysiological roles of chemokines in CNS, we have put forward
hypotheses on how chemokines may be involved in AD.
PMID- 10190689
TI - Chemokines and ocular pathology caused by corneal infection with herpes simplex
virus.
AB - The role played by chemokines in disease process is an active area of research
that continues to uncover new players. In this report we discuss the likely role
of selected chemokines in the disease herpetic stromal keratitis (HSK). This
lesion occurs as a sequel to herpes simplex virus infection and is currently
accepted as an immunopathological process which primarily involves CD4+ T
lymphocytes. In this review we discuss the events involved in HSK, the chemokine
profile associated with this disease, and speculate on cellular activities and
molecular events which characterize HSK as an immunopathological disease.
PMID- 10190690
TI - Inhibition of nitric oxide synthase-2 reduces the severity of mouse hepatitis
virus-induced demyelination: implications for NOS2/NO regulation of chemokine
expression and inflammation.
AB - Infection of C57BL/6 mice with mouse hepatitis virus strain V5A13.1 (MHV-V5A13.1)
results in an acute encephalitis followed by a chronic, progressive demyelinating
disease with clinical and histological similarities to the human demyelinating
disease Multiple Sclerosis (MS). Studies were undertaken to evaluate the
contribution of NOS2 generated NO in demyelination in MHV-infected mice. MHV
infected animals were treated daily with either 8 mg of aminoguanidine (AG), a
selective inhibitor of NOS2 activity, or PBS by intraperitoneal (i.p.) injection.
MHV-infection of mice resulted in 20% mortality in both groups with surviving
mice clearing virus below levels of detection, as measured by plaque assay, by
day 12 postinfection (p.i.). A significant decrease in the severity of clinical
disease was observed in AG-treated animals as compared to mice receiving PBS at
days 7 and 12 p.i. (P< or =0.001 and 0.003, respectively) however, by day 21 p.i.
AG-treated mice exhibited the same severity of clinical disease as control
animals. Examination of brain and spinal cords from infected mice revealed a
pronounced reduction in the severity of inflammation at day 7 p.i. in mice
treated with AG as compared to control mice. By day 12 p.i. there was a
significant decrease (P< or =0.02) in the severity of demyelination in AG-treated
mice as compared to control animals yet both PBS and AG treated mice had a
similar degree of demyelination by day 21 p.i. Analysis of chemokine mRNA
transcripts by RNase protection assay revealed that AG-treated mice had
significantly lower levels (P < or = 0.007) of transcripts for the C-C chemokine
monocyte chemoattractant protein-1 (MCP-1) at day 7 p.i. as compared to control
animals. By day 12 p.i., AG-treated mice and control mice had similar levels of
chemokine transcripts. Together, these data suggest that inhibition of NOS2/NO
slows the progression of MHV-induced demyelination. One potential mechanism by
which this may occur is through controlling inflammation through modulation of
chemokine expression in the CNS.
PMID- 10190691
TI - Differential chemokine induction by the mouse adenovirus type-1 in the central
nervous system of susceptible and resistant strains of mice.
AB - Mouse adenovirus-type 1 (MAV-1) has recently been shown to cause a fatal
hemorrhagic encephalopathy in certain strains of mice whereas other strains are
resistant. Morbidity is associated with a productive infection of cerebrovascular
endothelial cells, resulting in necrosis of the vasculature, infarction,
hemorrhage and death within 4 - 6 days. Previous studies were not able to define
a role for the innate or acquired immune response. In the current study we have
addressed the effect of MAV-1 on chemokine and chemokine receptor expression in
the central nervous system (CNS) and spleen of susceptible (C57BL/6) and
resistant (BALB/c) strains of mice. Intra-peritoneal infection with MAV-1 in
C57BL/6 animals resulted in early and prominent induction of IP-10/crg-2 in the
spleen and CNS. Increased expression of MCP-1, MIP-1alpha, MIP-1beta and RANTES
was also noted in the CNS of MAV-1-infected C57BL/6 animals commencing around 72
h post-infection. In contrast, chemokine expression in BALB/c animals was more
restricted with prominent upregulation only of MIP-2 in the CNS. In situ
hybridization identified the vascular endothelium and CNS glia as the principal
site of IP-10/crg-2 production in the C57BL/6 animals. The chemokine receptors
CCR1-5 were upregulated in the CNS of both strains of mice. These data show that
productive infection of the CNS with MAV-1 leads to the upregulation of a
characteristic pattern of chemokines and their receptors, which may point to a
role for these factors in disease pathogenesis.
PMID- 10190692
TI - Chemokines and the inflammatory response to viral infection in the central
nervous system with a focus on lymphocytic choriomeningitis virus.
AB - Leukocyte migration to the central nervous system (CNS) is a common process with
often devastating consequences that follows infection of this tissue compartment
with a variety of viruses. The mechanisms underlying this process are poorly
defined but, it is hypothesized that chemokines may be important regulatory
signals for the cerebral recruitment and extravasation of leukocytes. Here we
discuss this hypothesis in the context of different viral infections of the CNS
with emphasis on lymphocytic choriomeningitis virus (LCMV). In general, the
pattern of chemokine gene expression in these CNS viral infections is dynamic and
complex with often overlapping expression of a number of different subclasses of
chemokine genes. In the case of CNS infection with LCMV, cerebral chemokine gene
expression was observed in euthymic and to a lesser extent athymic mice and
preceded increases in cytokine gene expression and in euthymic mice, CNS
leukocyte recruitment. These observations together with the finding that CRG-2/IP
10, a prominently expressed chemokine gene in many different CNS viral
infections, was expressed by cells intrinsic to the CNS e.g. astrocytes, suggest
that activation of chemokine gene expression may be a direct, early and localized
host response to viral infection. These findings are consistent with the proposed
involvement of chemokines as key signaling molecules for the migration of
leukocytes to the CNS following virus infection.
PMID- 10190693
TI - Dissemination of C. neoformans to the central nervous system: role of chemokines,
Th1 immunity and leukocyte recruitment.
AB - Cryptococcus neoformans is a fungus that possesses two properties unique for
yeast: (1) production of a polysaccharide capsule and (2) neurotropism. The
natural route of infection by C. neoformans is the respiratory tract; thus,
factors that regulate the development and recruitment of memory Th1 cells and
monocytes into the brain are critical for an effective response against
disseminated C. neoformans infection. Production of TNFalpha prior to day 7 is
required to prevent colonization of the central nervous system (CNS). Th1 type
immunity is required to clear established foci. In contrast, Th2 type immunity is
ineffective at eliminating the infection in the brain and results in decreased
survival. C. neoformans infection of MIP-1alpha and CCR5 knockout mice has
highlighted the complex role that some chemokines may play in different organs.
MIP-1alpha knockout mice have decreased leukocyte recruitment and cryptococcal
clearance from the brain compared to wild-type mice. Thus, the host defence
mechanisms that clear C. neoformans from the CNS appear to be similar to those in
the lungs: via a Th1 cell-mediated inflammatory response that requires chemokines
for the recruitment of effector cells.
PMID- 10190694
TI - Cytokine regulation of CC and CXC chemokine expression by human astrocytes.
AB - Chemokines constitute a large family of secreted proteins that function as
chemoattractants and activators of leukocytes. Astrocytes, the major glial cell
type in the central nervous system (CNS), are a source of chemokine production
within diseased brain. As such, we have examined the production of chemokines by
human astroglioma cell lines and primary human astrocytes treated with a variety
of stimuli, including LPS, TNF-alpha, IFN-gamma and IL-1beta. In addition, IL-6
in conjunction with the soluble IL-6 receptor (sIL-6R), and hybrid IL-6 (H-IL-6),
a highly active fusion protein of sIL-6R and IL-6, were tested for their ability
to induce chemokine expression. The findings presented herein demonstrate that
both human astroglioma cell lines and primary human astrocytes express the CXC
chemokines IP-10 and IL-8 and the CC chemokines MCP-1 and RANTES in response to
TNF-alpha and IL-1beta. IFN-gamma induced the expression of IP-10, but not of IL
8, MCP-1 or RANTES. Surprisingly, IL-6/sIL-6R and H-IL-6 had little or no effect
on chemokine expression in these cells. The effect of TGF-beta on chemokine
expression in human astroglioma cell lines and astrocytes was also examined. TGF
beta alone had little or no effect on RANTES, MCP-1 and IL-8 expression; however,
TGF-beta synergized with TNF-alpha to enhance MCP-1 expression in both
astroglioma cells and primary astrocytes. An inhibitory effect of TGF-beta on TNF
alpha and IL-1beta induced RANTES and IL-8 expression was observed in human
astroglioma cells. In contrast, TGF-beta enhanced TNF-alpha and IL-1beta
induction ofIL-8 production by human astrocytes. These findings document a
complex pattern of chemokine regulation by the pleiotropic cytokine TGF-beta with
both enhancing and inhibitory effects.
PMID- 10190695
TI - Chemokine expression in GKO mice (lacking interferon-gamma) with experimental
autoimmune encephalomyelitis.
AB - Experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease of the
central nervous system (CNS) considered to be an animal model for multiple
sclerosis (MS). The detailed mechanism that specifies accumulation of
inflammatory cells within the CNS in these conditions remains a subject of active
investigation. Chemokines including IP-10, GRO-alpha, MCP-1 are produced in EAE
tissues selectively by parenchymal astrocytes, but the regulatory stimuli that
govern this expression remain undetermined. The unexpected occurrence of
increased EAE susceptibility in Balb/c GKO mice (lacking IFN-gamma) offered an
opportunity to examine the spectrum of chemokine expression during immune
mediated inflammation in the absence of a single regulatory cytokine. We found
that chemokines MCP-1 and GRO-alpha were upregulated in the CNS of mice with EAE
despite the GKO genotype. IP-10, which is highly expressed in the CNS of mice
with an intact IFN-gamma gene and EAE, was strikingly absent. In vitro
experiments confirmed that IFNgamma selectively stimulates astrocytes for IP-10
expression. These results indicate that IP-10 is dependent upon IFN-gamma for its
upregulation during this model disease, and document directly that astrocyte
expression of chemokines during EAE is governed by pro-inflammatory cytokines.
PMID- 10190696
TI - Chemokines in chronic progressive neurological diseases: HTLV-1 associated
myelopathy and multiple sclerosis.
AB - It is hypothesized that in MS and HTLV-1, chemokine and chemokine receptor
expression are important mechanisms by which T cells migrate to sites of
inflammation. Preliminary evidence supports the roles of several chemokines,
including MIP 1beta, in mediating the enhanced migration capacity of MS derived
PBLs. In addition, the ligand CCR-5 seems to be up regulated on PBLs from some MS
patients. Analysis of T cell clones does not reveal a definite correlation
between cytokine phenotype and chemokine receptor profile. The chemokines and
chemokine receptor family are likely to be important molecules in chronic
progressive neurological diseases, in which immune cells invade the central
nervous system.
PMID- 10190697
TI - Symposium on Multiple Sclerosis: new dimensions in basic research and their
clinical applications. November 2, 1998. Philadelphia, Pennsylvania.
PMID- 10190698
TI - The effect of platelet-derived growth factor on tracheal wound healing.
AB - In order to evaluate a new method for the direct application of a polypeptide
growth factor to injured tracheal epithelium and to determine the effect of
topical platelet-derived growth factor (PDGF) on tracheal wound healing, a
controlled animal study was designed using six adult beagle dogs. Four 2x1 cm
mucosal defects were created in the tracheal lumen of each dog for a total of 24
experimental sites. Twelve wounds were treated with PDGF in a collagen-fibrin
composite tissue adhesive (CTA) carrier. Eight sites received CTA alone and four
were left untreated. Healing was assessed by endoscopic exam on post-operative
days 4, 7, 10, 14, 17 and 21. The animals were sacrificed on day 21 and the
tracheas were harvested for histological examination of the experimental sites
and adjacent unwounded trachea. By 21 days, complete healing of all sites was
observed endoscopically. Wounds treated with CTA or PDGF-CTA healed at a faster
rate than control sites. The PDGF-CTA treated wounds demonstrated excessive
granulation tissue formation. Histological examination demonstrated a higher
percentage of wound coverage with ciliated epithelium most similar to normal
trachea in the PDGF treated wounds. CTA is effective as a carrier for the direct
delivery of a growth factor to injured tracheal epithelium. The application of
CTA or PDGF-CTA results in a more rapid rate of tracheal wound healing as
compared with control wounds. PDGF-CTA led to increased acute local inflammatory
changes but was associated with a structurally more normal respiratory epithelium
after healing. Physiological studies are necessary to determine the functional
significance of these findings.
PMID- 10190699
TI - Outpatient management of acute mastoiditis with periosteitis in children.
AB - Children with acute mastoiditis with periosteitis are conventionally hospitalized
for parenteral antibiotics and/or surgical treatment. However, if possible,
effective and safe outpatient treatment is desirable. During a 36-month period,
outpatient parenteral antibiotic therapy (once daily i.m. ceftriaxone) was
evaluated in 32 children with acute mastoiditis, with clinical evidence of
periosteitis. Inclusion criteria included otomicroscopic evidence of acute otitis
media (AOM), displacement of the pinna, retroauricular swelling, erythema and
tenderness. The treatment consisted of wide myringotomy and administration of
i.m. antibiotics. Daily visits, by a combined team of an otolaryngologist and
pediatric infectious disease specialist, were considered essential. Fourteen
children (43%) were treated initially in the hospital (and subsequently as
outpatients) and 18 (57%) children were treated entirely as outpatients. Mean
duration of outpatient treatment was 7 days (range: 4-10). The overall clinical
cure rate was 96.8%. One child underwent simple mastoidectomy. No serious side
effects were observed. Our data suggests that many children with acute
mastoiditis with periosteitis can be managed successfully and safely as
outpatients by a combined team of otolaryngologists and infectious disease
specialists.
PMID- 10190700
TI - Nasal gliomas: main features, management and report of five cases.
AB - Nasal gliomas are neurologic malformations that should be considered in the
presence of a congenital nasal mass. Appropriate pre-operative examination must
be performed to identify a possible connection with CNS, which is present in 15
20% of the cases. This examination should determine whether initial craniotomy is
necessary. Here, we report five cases and review the main characteristics and
management of this pathology.
PMID- 10190701
TI - Laryngomalacia: a proposed classification form.
AB - Laryngomalacia is a common cause of stridor in children. The disorder has a
heterogenous presentation, from the mildest form, which resolves with maturation,
to the most severe form, requiring tracheotomy. While there is a vast literature
on the subject, there is neither stratification nor correlation of clinical
presentation, endoscopic appearance, treatment and outcome. In order to
statistically evaluate the choice of treatment based upon presentation, patients
must first be classified by relevant predictors of disease severity. A form is
proposed to classify the clinical presentation of laryngomalacia by recording
relevant historical and anatomic factors. Historical factors are classified by
(1) severity of stridor; (2) weight gain; (3) age at presentation; and (4)
neurologic status, forming the mnemonic SWAN. The principal anatomic site of
collapse is recorded as: (1) postero-lateral; (2) posterior; or (3) anterior.
Endoscopic findings consistent with gastroesophageal reflux disease (GERD) or
gross aspiration are noted. Photographic and/or video documentation is performed
when possible. A pilot study was undertaken to determine the ease of use of this
instrument. Ten children, four boys and six girls, were classified. Ages ranged
from 1-day-old to 19 months, with a mean of 9 months. Five children were examined
in the clinic and five in the operating room. The form was readily and easily
applied, and allowed the heterogeneity of the disorder to be organized. Wider
application of this form across institutions, with classification of patients
with laryngomalacia by historical and anatomic factors, should allow the
accumulation of sufficient numbers of patients to allow statistical analyses of
treatment and outcome as they relate to the initial presentation of this disorder
of airway dynamics.
PMID- 10190702
TI - Unilateral choanal atresia: initial presentation and endoscopic repair.
AB - The purpose of this study was to investigate the severity of presenting
symptomatology in patients with unilateral choanal atresia and to assess the
surgical results of patients undergoing transnasal endoscopic repair. A
retrospective review of all patients with choanal atresia presenting to the
author between 1990 and 1997 was performed, identifying 13 patients with
unilateral choanal atresia. These patients were analyzed with respect to
presenting symptomatology, preoperative computed tomography scans, appearance,
type of surgical repair, and surgical results for patients undergoing endoscopic
transnasal repair. Eleven patients underwent successful endoscopic transnasal
repair, one patient underwent conversion to transpalatal repair after an
unsuccessful attempt at transnasal endoscopic repair and one patient underwent a
planned transpalatal repair. Eleven patients who underwent repair by transnasal
endoscopic technique have all done well with follow-up ranging from 3 months to 7
years. Although the symptomatology of unilateral choanal atresia is not as
dramatic as bilateral choanal atresia, significant airway symptomatology may be
present, especially in children presenting at a very young age. It appears that
transnasal repair of unilateral choanal atresia is an excellent treatment
modality with excellent postoperative surgical results.
PMID- 10190703
TI - Ear and nose foreign body removal in children.
AB - The removal of foreign bodies in children is very common in the
otolaryngologist's daily routine. We present a prospective series of 187 cases of
ear and nose foreign bodies removed from children aged 0-12 years old in a 6
month period--95 females (50.8%) and 92 males (49.2%); 78 children (41.71%) aged
from 1 to 2 years, 66 (35.29%) from 3 to 5 years. There were 93 cases (49.73%) of
ear foreign bodies, in which a bean was the most common (24.73%), and 94 cases
(50.27%) of nose foreign bodies, in which sponge fragments predominated (36.17%).
In 82 cases (45.85%), the removal was performed within the first 24 h after the
foreign body insertion, and 86 (45.98%) of the patients had previous attempts to
remove it. Thirteen cases with complications (external ear canal lacerations,
tympanic membrane perforation) were observed in patients in whom these previous
attempts had been made, but there were no sequelae. This corresponds to one of
the largest reports of ear and nose foreign body removal in children in the
literature; we conclude that younger children are more prone to insert foreign
bodies, which are objects usually found at home. Complications may occur as a
result of attempts to remove the foreign body without the help of specialised
personnel or proper conditions.
PMID- 10190704
TI - A study of auditory afferent organization in children with dyslalia.
AB - The auditory afferent (AA) control is an important feedback mechanism in the
speech generation. A different organization of AA pathways in children with
speech alterations is suggested. In order to investigate this possibility we
recorded the auditory brainstem responses (ABR) and middle latency responses
(MLR) on monoaural and binaural click stimulation in a group of 17 normal
children with no alteration of the speech (N) and in 16 children with dyslalia
(eight with systematic (S) and eight with non-systematic errors of the speech
(NS)). All of children were normal hearing, with normal ORL and neurological
status, right-handed and with the age approximately 7 years old. A lateralization
effect was found in the S group. Normally, it was only found for wave I. The
efficiency of both AA pathways was the same in NS group, indicating a more
effective right pathway in more rostral areas. A prolonged latency (X = 0.25 ms)
of wave III was registered on the right side in the NS group compared to normals,
as well for wave V (X = 0.175 ms) with increased sweep rate (21 vs. 51 and 71).
The effect of sweep rate augmentation was also studied (21-51-71) on latency
values and inter-wave differences in these groups. A successive latency
prolongation (X = 2.97 ms) of MLR wave Na was registered between the N-S-NS
groups. In the S group a latency binaural interaction (BI) of MLR left wave Na
was prolonged for 3.52 ms and in the NS group for a further 1.32 ms compared to
normals. Only in the NS group was a prolongation of the BI of the right wave Pa
detected (6.76 ms) compared to normals. Results suggest a different AA
organization in children with dyslalia. Possible locations of alterations in
functioning could be pons, and thalamocortical projections. ABR and MLR could
evaluate the auditory-speech capability of children.
PMID- 10190705
TI - Risk factors for recurrent and residual cholesteatoma in children determined by
second stage operation.
AB - OBJECTIVE: To clarify the risk factors for the development of recurrent and
residual cholesteatoma in children. METHODS: We studied 84 ears of 83 children
aged 10 years or younger who underwent a second stage operation 1 year after
primary surgery with a canal wall reconstruction procedure, and analyzed the
clinical risk factors for recurrent and residual cholesteatoma. RESULTS:
Recurrent cholesteatoma was detected in 21 ears (25%) and residual cholesteatoma
was noted in 35 (42%) of 84 ears. With respect to recurrent cholesteatoma,
significant risk factors were determined to be male gender, pars flaccida type of
cholesteatoma and the association of otitis media with effusion either in the
side affected by cholesteatoma or on the opposite side. On the other hand,
congenital type of cholesteatoma was a significant negative risk factor. With
respect to residual cholesteatoma, the only risk factor was a posterosuperior
type of cholesteatoma. Residual cholesteatoma was sometimes found even when the
surgeon had declared complete removal of the cholesteatoma matrix at the time of
primary surgery. CONCLUSIONS: High incidence of recurrent and residual
cholesteatoma was noted at the second stage operation. Occurrence of recurrent
cholesteatoma is closely related to eustachian tube dysfunction. Thin and highly
proliferative cholesteatoma matrix in children may be responsible for high
occurrence of residual cholesteatoma. Therefore, planned staged surgery is
preferable to single stage surgery for the treatment of pediatric cholesteatoma.
PMID- 10190706
TI - DNA ploidy in papillary carcinoma of the thyroid gland in children and
adolescents.
AB - OBJECTIVE: To evaluate DNA ploidy in papillary thyroid carcinoma in children in
correlation to the clinical course of the disease. METHODS: Flow cytometric DNA
ploidy measurements were performed on formalin-fixed, paraffin-embedded tumor
specimens from 14 children and 14 adult patients with papillary carcinoma of the
thyroid gland. Analysis of DNA content was performed blind to patient's age and
clinical presentation. RESULTS: Seven patients presented with cervical
metastasis, one patient had distal metastasis and four patients had local
invasion. All patients underwent total thyroidectomy. Seven children underwent
bilateral modified neck dissection. Twenty-five tumors expressed diploid DNA
content. No statistically significant difference in DNA content was observed
between the tumors from child and adult patients. No correlation was found
between DNA content and aggressive presentation in the pediatric group.
CONCLUSION: Our primary results indicate that diploid DNA content is common in
papillary thyroid carcinoma in children and aggressive clinical presentation is
not associated with DNA aneuploidy. Larger prospective studies and long-term
clinical follow-up is warranted to document the clinical significance of these
observations.
PMID- 10190707
TI - Implications of developmental plasticity for the language acquisition of deaf
children with cochlear implants.
AB - The study of language acquisition in profoundly deaf children with cochlear
implants informs us about the developmental plasticity of the auditory system.
Sensory activity leads to neural development, and the sustained effects of
sensory inactivity can lead to a loss of responsiveness. These effects may be
reversed by the subsequent provision of sensory stimulation, such as that
delivered by cochlear implants. Behavioral and electrophysiological research on
the effects of speech deprivation on language acquisition shows that the age and
modality of language acquisition is an important determinant of adult linguistic
performance. Studies on profoundly deaf children deprived of speech stimulation,
and then provided with a cochlear implant giving them access to the speech
frequencies, shows that congenitally deaf children implanted under the age of
around 5 years are likely to perform better on speech perception and speech
production tasks than children implanted at an older age. Further investigation
is required to understand why these large individual differences exist. In
addition, other key issues for research are the effects of compensatory visual
and somatosensory development prior to implantation, whether there is a
maturational delay that approximates to the period of speech deprivation prior to
implantation, and whether there are a number of sensitive periods that together
describe the cascade of processes that underlies language acquisition.
PMID- 10190708
TI - Hearing screening in at-risk neonate cohort.
AB - OBJECTIVE: This prospective study reports on the prevalence of hearing impairment
in an at-risk neonatal intensive care unit (NICU) population. DESIGN: From 1990
to 1997, 942 neonates were screened with transient evoked otoacoustic emissions
(TEOAE) and brainstem evoked response audiometry (BERA). RESULTS: 835 Infants
passed the primary screen for both ears, 57 for one ear, adding up to 94.7%.
Seventeen infants (1.9%) were lost to follow-up. In thirteen infants (1.4%),
bilateral hearing impairment above 30 dB was confirmed. While all children with
hearing impairment belonged to the group of 820 children receiving
aminoglycosides, only one presented no other risk factors. In 11 of the hearing
impaired children other anamnestic factors, i.e. dysmorphism, prenatal rubella or
cytomegaly, family history of hearing loss or severe peri- and postnatal
complications seem to be more probable causes of the identified hearing loss.
CONCLUSIONS: From our data, aminoglycosides seem not to be an important risk
factor for communication related hearing impairment, when serum levels are
continuously monitored, as occurred in our cohort. After adjustment for other
risk factors, birth weight between 1000 and 1500 g and a gestational age between
29 and 31 weeks were no predictive markers for hearing impairment. It might be
speculated that the improved medical treatment in a Neonatal Intensive Care Unit
(NICU) reduces the probability of hearing impairment for those two groups.
Conductive hearing loss as a possible additional cause for hearing impairment was
not studied in detail, but the high percentage of malformations detected (four
out of 13 hearing impaired infants) demands further monitoring, close follow-up,
counselling and adequate treatment.
PMID- 10190710
TI - Aberrant second branchial cleft fistula.
AB - Second branchial cleft cysts and sinuses rarely present diagnostic problems to
the pediatric otolaryngologist as their course is usually predictable based on
consistent embryologic development. However, we evaluated two fistula tracts that
did not fit the classic description of second branchial tract fistulas. Upon
radiographic and intraoperative evaluation, their eventual course ending in the
tonsillar fossa was identified. Realizing the potential for aberrancy and using
preoperative radiographic evaluation will assist the surgeon in the excision of
these developmental anomalies with little risk to underlying neurovascular
structures.
PMID- 10190709
TI - Topical ofloxacin versus systemic amoxicillin/clavulanate in purulent otorrhea in
children with tympanostomy tubes.
AB - Acute otitis media (AOM) in children with tympanostomy tubes in place typically
presents with otorrhea (draining ear). Because therapy is not standardized,
various topical and systemic antibiotics of unproven efficacy and safety have
been used in this indication. This study compared the safety and efficacy of
ofloxacin otic solution, 0.3% (OFLX) with that of Augmentin oral suspension (AUG)
in pediatric subjects 1-12 years of age with tympanostomy tubes and acute
purulent otorrhea. Subjects were randomized to receive 10d of OFLX, 0.25 ml
topically bid, or of AUG, 40 mg/kg per day. Audiometry was performed in subjects
> or =4 years of age. Overall cure rate for clinically evaluable subjects was 76%
with OFLX (n = 140) and 69% with AUG (n = 146; P = 0.169). Overall eradication
rates for OFLX and AUG were similar for Streptococcus pneumoniae, Haemophilus
influenzae and Moraxella catarrhalis and were superior with OFLX for
Staphylococcus aureus and Pseudomonas aeruginosa (P<0.05 for both). OFLX had a
greater overall pathogen eradication rate (96% vs. 67%; P<0.001). Treatment
related adverse event rates were 31% for AUG and 6% for OFLX (P<0.001). Neither
treatment significantly altered hearing acuity. Topical ofloxacin 0.3% otic
solution 0.25 ml bid was as effective and better tolerated than systemic therapy
with Augmentin oral suspension 40 mg/kg per day in treating AOM in children with
tympanostomy tubes.
PMID- 10190711
TI - Labyrinthine involvement in Langerhans' cell histiocytosis.
AB - BACKGROUND: Langerhans' cell histiocytosis, a rare condition caused by the
proliferation of abnormal Langerhans' cells ('LCH cells') and an accompanying
granulomatous infiltrate, can affect several organs including the ear. External
and middle ear involvement are common with a reported incidence as high as 61%.
The bony labyrinth is resistant to erosion by the granulation tissue, thereby
protecting the cochlea and vestibular structures. Probably for this reason,
involvement of the inner ear is rare, with few case reports in the literature.
PATIENTS: We report two girls, one with bilateral and the other with unilateral
mastoid involvement, in whom there was invasion of the labyrinth. The first girl
had 'single system' LCH affecting only bone and developed an acute hearing loss
due to invasion of the cochlea, while the second had both bone and skin
involvement and labyrinthine involvement was diagnosed on imaging prior to the
onset of labyrinthine symptoms. CONCLUSION: Inner ear involvement can lead to
permanent deafness, which may be prevented by early institution of treatment.
Threatened inner ear involvement requires urgent systemic medical therapy with
steroids, possibly combined with chemotherapy.
PMID- 10190712
TI - Polyotia--a rare external ear anomaly.
AB - A rare case of polyotia in a 7-year old boy associated with first arch syndrome
is reported. The accessory auricle formed a well defined helix and conchal bowl
located anterior to a normal auricle and an atretic external auditory meatus.
Surgical resection and reconstruction resulted in a good cosmetic outcome.
PMID- 10190713
TI - Subdural empyema and blindness due to cavernous sinus thrombosis in acute frontal
sinusitis.
AB - In this era of antibiotics, the complications of acute sinusitis are much less
frequently encountered. Although orbital complications are most common,
intracranial complications carry a high rate of mortality and morbidity. We
describe a case of acute frontal sinusitis with subdural empyema and blindness
due to cavernous sinus thrombosis and carotid artery thrombosis with a discussion
of treatment of these complications and the etiology of blindness in sinusitis.
PMID- 10190714
TI - The presence of high amounts of HBV-DNA in serum is associated with suppressed
costimulatory effects of interleukin 12 on HBV-induced immune response.
AB - BACKGROUND/AIMS: The aim of this study was to examine the influence of the viral
load on costimulatory effects of rhIL-12 on the hepatitis B virus (HBV)-induced
immune response. METHODS: Peripheral blood mononuclear cells of HBsAg positive
patients without cirrhosis were stimulated with HBsAg, HBcAg, preS1Ag and tetanus
toxoid in the absence or presence of IL-12 (0.01, 0.1 and 1 ng/ml). Stimulation
by alpha-CD3+alpha-CD28, pokeweed mitogen (PWM) and lipopolysaccharide (LPS) were
used as controls. Then, proliferation and cytokine production were determined by
3H-thymidine uptake and ELISA after 72 h. The patients were divided into group 1
(n=21): HBV-DNA: not detectable, group 2 (n=13): HBV-DNA: <300 pg/ml, and group 3
(n= 10): HBV-DNA: >300 pg/ml. RESULTS: After stimulation with only HBV antigens,
the highest amounts of IL-10 were found in group 3, while interferon (IFN)-gamma
was rarely detectable. After stimulation with IL-12 and HBV antigens, strong
costimulatory effects on IFN-gamma production, as well as proliferation, were
observed in all patients except individuals from group 3. With regard to antigen
unrelated stimulation, significantly lower amounts of LPS-induced IFN-gamma
production and alpha-CD3+28 induced proliferative responses, but higher amounts
of LPS-induced IL-10 were observed in group 3. CONCLUSIONS: These data suggest
that the presence of high amounts of HBV-DNA in serum is associated with
suppressed co-stimulatory and regulatory effects of IL-12 on the immune response
to HBV antigens. This may be one explanation for the poor response to
immunostimulating therapy in patients with a high viral load.
PMID- 10190715
TI - In situ detection of mutated hepatitis B virus in microdissected, formalin-fixed
liver tissues from patients with chronic hepatitis B.
AB - BACKGROUND/AIMS: Hepatitis B virus (HBV) quasispecies have been detected in
patients with chronic hepatitis B. In order to elucidate the relationship between
HBV mutation and liver cell necrosis in situ, we analyzed sublobule-sized
specimens microdissected from formalin-fixed paraffin-embedded liver biopsy
tissues taken from patients with chronic hepatitis B. METHODS: The subjects were
20 patients with chronic hepatitis B. We extracted HBV-DNA from two sublobular
regions of HBV-infected liver biopsy tissue, those with the most severe and the
mildest hepatitis activity, demonstrated microscopically. The DNA coding sequence
of the precore-core region of HBV was determined by amplifying the DNA by the
polymerase chain reaction, followed by direct sequencing. RESULTS: In all seven
patients with minimal to mild hepatitis activity, but only 4 of 13 with moderate
to severe activity, the amino acid sequence of the precore-core region of HBV
obtained from the region with the most severe hepatitis activity showed over 99%
homology with the corresponding sequence of HBV obtained from region with the
mildest hepatitis activity (p<0.05). CONCLUSION: The differences between
intrahepatic HBVs observed in patients with highly active hepatitis suggest that
exacerbation of hepatitis in vivo is related to the appearance of variants in the
precore-core region of HBV.
PMID- 10190717
TI - Ribavirin polarizes human T cell responses towards a Type 1 cytokine profile.
AB - BACKGROUND/AIMS: The therapeutic benefit of ribavirin, a nucleoside analog, in
the treatment of chronic HCV infection is seen even in the absence of any
apparent direct antiviral effect. We surmised that ribavirin may act by eliciting
altered virus-specific immune responses. Because antiviral immunity is
predominantly mediated by cytotoxic T cells and antiviral cytokines, we sought to
determine whether ribavirin could promote antiviral (Type 1) cytokine expression
in human T cells. METHODS: Isolated human T cells were activated in vitro with
enterotoxin B or with phorbol ester plus ionomycin. Cytokine ELISAs were
performed on culture supernatants, cytokine mRNA was detected following RT
polymerase chain reaction of T cell RNA, and T cell proliferation measured using
MTT assay. RESULTS: Ribavirin enhanced a Type 1 (IL-2, IFNgamma, TNFalpha) while
suppressing a Type 2 cytokine response (IL-4, IL-5 and IL-10), at the level of
both protein and mRNA expression. Ribavirin mediated comparable effects on
cytokine expression both following activation of specific T cell subpopulations
with superantigen and following activation of a larger percentage of T cells via
pharmacologic means. The in vitro effect on cytokine expression following
ribavirin treatment was comparable in both CD4+ or CD8+ T cell subsets and was
observed in a dose range that promoted T cell proliferation. CONCLUSIONS: These
data support the view that ribavirin promotes a Type 1 cytokine-mediated immune
response, a property which may account in part for its ability to enhance the
antiviral activity of interferon-alpha in the treatment of chronic HCV infection.
PMID- 10190716
TI - Epitope mapping of cytochrome P4502D6 autoantigen in patients with chronic
hepatitis C during alpha-interferon treatment.
AB - BACKGROUND/AIMS: Cytochrome P450 2D6 (CYP2D6) has been documented as the major
target antigen of liver kidney microsomal autoantibodies type-1 (anti-LKM-1) in
both autoimmune hepatitis type-2 (AIH-2) and hepatitis C (HCV). In HCV/anti-LKM-1
positive patients, the choice between alpha-interferon (alpha-IFN) or
immunosuppression may be difficult. This study was conducted to evaluate the
course and outcome of alpha-IFN therapy in HCV/anti-LKM-1-positive and -negative
patients and the alterations in these autoantibody titers by the indirect
immunofluorescence and a novel radioligand assay. Epitope mapping was also
performed to screen for a potential shift in anti-LKM-1 binding towards small
linear epitopes, which are more often detected in AIH-2 patients. METHODS: Twenty
one patients with HCV infection received alpha-IFN. Seven patients were anti-LKM
1 positive (study group) and 14 patients were anti-LKM-1 negative (disease
control group). Anti-CYP2D6 detection was based on immunoprecipitation of [35S]
methionine-labeled CYP2D6 recombinant protein (rCYP2D6) produced by in vitro
transcription/translation. RESULTS: Four out of seven (57%) patients in the study
group and 5/14 (36%) in the disease control group initially responded, but
subsequently relapsed. During follow-up, alanine aminotransferase significantly
increased in the study group compared to the disease control group (p<0.01). A
slight increase, followed by a plateau of autoantibody titers was recorded by the
radioligand assay and by indirect immunofluorescence during therapy and follow-up
in most cases. In one patient, however, gamma-globulins and anti-LKM-1 titers
increased, reaching very high levels (1:40 960). alpha-IFN was interrupted and
immunosuppression was started. HCV/anti-CYP2D6 positive sera recognized CYP2D6
expressed in E. coli and two truncated proteins (aa 250-494 and 321-494). Two out
of seven sera, in addition reacted with a small linear epitope of aa 257-269 (one
of which also reacted with a C-terminal domain of aa 350-494). CONCLUSIONS: A
rather mild deterioration in liver disease was observed in only 1/7 HCV/anti-LKM
1-positive patients during alpha-IFN treatment. This patient showed high anti
CYP2D6 titers before the initiation of therapy, a sharp increase in anti-LKM-1
titers during treatment, and reactivities to a small linear epitope and an
infrequently recognized C-terminal domain of CYP2D6. After switching to
immunosuppressive treatment, a complete and sustained response was recorded.
Further prospective studies from many centers are needed to define whether these
features have general, clinical significance or not.
PMID- 10190718
TI - Absence of the negative strand of GBV-C/HGV RNA from the liver.
AB - BACKGROUND/AIMS: The pathogenic role of the human virus GBV-C/HGV remains unclear
as information on tissue specific tropism and sites of replication of GBV-C/HGV
is limited and controversial. The aim of this study was to determine whether the
liver is the site of GBV-C/HGV replication. METHODS: We utilized the strand
specific Tth RT-PCR assay to investigate the presence of the positive- and
negative-strand of GBV-C/HGV RNA in liver and serum samples from 12 patients with
chronic GBV-C/HGV infection; four were infected with GBV-C/HGV alone, six were
coinfected with HCV and two with HBV. A control group of six patients infected
with HCV alone was included. The presence of the positive- and negative-strand of
HCV RNA was also investigated in the same samples. RESULTS: All liver specimens
were negative for the presence of the replicating negative-strand of GBV-C/HGV
RNA. Positive-strand GBV-C/HGV RNA was found in 6 of the 12 liver samples and was
detectable only at low levels, most probably reflecting serum contamination. By
contrast, the negative strand of HCV RNA was detected in high titers in the liver
of all HCV-infected and -coinfected subjects with less than a 100-fold difference
from the positive strand. In serum samples only the positive strands of GBV-C/HGV
and HCV RNA were detected in comparable titers. CONCLUSIONS: The results of this
study suggest that GBV-C/HGV is not replicating in the liver and, taken together
with the bulk of evidence against hepatopathogenicity, they argue against the new
agent being a hepatotropic virus. We suggest that the acronymic term of this
agent GBV-C/HGV is used with the understanding that it is not a hepatitis virus.
PMID- 10190719
TI - TT virus infection among blood donors and patients with non-B, non-C liver
diseases in Korea.
AB - BACKGROUND/AIMS: A novel virus, designated the TT virus (TTV), was isolated from
the serum of a patient with posttransfusion hepatitis of unknown etiology, in
Japan. Subsequently, TTV was suggested to be a causative agent in a proportion of
cases with cryptogenic hepatitis in Japan. This study aimed to elucidate the
significance of TTV infection in cases with cryptogenic liver disease in Korea, a
neighbor of Japan. METHODS: The prevalence of TTV infection was studied in 120
patients with liver diseases, including 85 patients diagnosed as having non-B,
non-C liver diseases. As controls, 220 blood donors were also examined. TTV DNA
was detected by polymerase chain reaction, and the sequence was analyzed by
phylogenetic analysis. RESULTS: Fourteen (14.0%) of 100 accepted blood donors, 23
(19.2%) of 120 rejected blood donors, and 15 (17.6%) of 85 patients with non-B,
non-C liver diseases were positive for TTV DNA. The prevalences of TTV infection
among these groups were not significantly different. Phylogenetic analysis
suggested the existence of four major genotypes of TTV The proportions of each
genotype among patients with non-B, non-C liver diseases were not different from
those among accepted blood donors. CONCLUSIONS: TTV exists in Korea, but the
prevalence among patients with non-B, non-C liver diseases was almost the same as
that among blood donors. TTV may not be the main causative agent of cryptogenic
liver disease in Korea. The relationship between non-B, non-C liver diseases and
TTV genotype remains unclear, although TTV can be classified into four genotypes.
PMID- 10190720
TI - Behavior and significance of autoantibodies in type 1 autoimmune hepatitis.
AB - BACKGROUND/AIM: Smooth muscle antibodies and antinuclear antibodies characterize
type 1 autoimmune hepatitis. Our aim was to correlate the appearance and
disappearance of these autoantibodies with clinical and histological events.
METHODS: One hundred and seven patients were evaluated successively over 128+/-9
months. Autoantibodies were determined by indirect immunofluorescence during
routine follow-up and at key clinical events. RESULTS: Eighty-one patients (76%)
lost one or both of the autoantibodies, and disappearance was associated with
improved laboratory and histological features. Autoantibody status, however, was
not highly predictive of laboratory (69%) or histological activity (72%).
Patients who relapsed were seronegative at the time of drug withdrawal as
commonly as patients who sustained remission (29% versus 25%). Only 27 patients
(25%) lost their autoantibodies long term. Patients who eventually entered a
sustained remission lost their autoantibodies more commonly than those who
required retreatment (76% versus 43%, p=0.03). Disappearance of the
autoantibodies, however, preceded sustained remission in only 38%. Serum titers
at presentation did not distinguish patients with more severe disease or
different treatment outcomes. CONCLUSIONS: Smooth muscle antibodies and
antinuclear antibodies commonly disappear and reappear. Their loss is associated
with improved laboratory tests and biopsy findings, but disappearance does not
predict treatment outcome. Autoantibody titer at presentation and autoantibody
behavior during therapy are not accurate indices of disease severity or
prognosis.
PMID- 10190721
TI - Familial primary biliary cirrhosis reassessed: a geographically-based population
study.
AB - BACKGROUND/AIMS: Development of primary biliary cirrhosis in the close relatives
of patients with the disease has been reported in several series, suggesting a
genetic component to disease susceptibility. In this study we set out to
calculate, as accurately as possible, the prevalence of familial primary biliary
cirrhosis in a geographically-based population. Using local population prevalence
data, we have also calculated the first-degree relative, sibling and offspring
relative risks of overt primary biliary cirrhosis development. METHODS: All
patients with definite or probable primary biliary cirrhosis in the city of
Newcastle-upon-Tyne, England, were identified by an exhaustive case-finding
search and were prospectively interviewed by a single investigator. Full details
of family pedigree and familial primary biliary cirrhosis history were obtained.
RESULTS: One hundred and seventy-three patients were identified, with 160
participating in the study. Thirteen reported a family history of primary biliary
cirrhosis. In three cases, both relative pairs were within the study group. The
prevalence of a positive family history of primary biliary cirrhosis was
therefore 10/157 (6.4% [95% Confidence Interval 2.6-10.2%]), 8/10 cases occurring
in first-degree relatives. The patients had a total of 1118 first-degree
relatives (live or dead) and 468 siblings. The first-degree relative prevalence
of primary biliary cirrhosis was 0.72% [0.2-1.2%] (siblings 0.41% [-0.2-1.0%]).
The offspring prevalence was 1.2% [0.04-2.4%], (2.3% [0.1-4.5%] for daughters).
The sibling relative risk (lambda(s)) was 10.5. CONCLUSIONS: The overall
prevalence of definite or probable primary biliary cirrhosis in the first-degree
relatives of existing patients is <1%. The risk of disease is not, however,
uniform, the highest prevalence being seen in the daughters of patients.
Suspicion of disease should therefore be highest in this relative group. The
calculated lambda(s) for primary biliary cirrhosis in this geographically-based
study is significantly lower than previous estimates from case-note-derived case
series, but similar to values seen in other autoimmune diseases.
PMID- 10190722
TI - Clinical and biochemical expression of the histopathological lesions of primary
biliary cirrhosis. UDCA-PBC Group.
AB - BACKGROUND/AIMS: This study aimed to assess the relationships which may link
elementary histological lesions with symptoms and biochemistries in primary
biliary cirrhosis. METHODS: We studied 103 patients with primary biliary
cirrhosis who participated in a double-blind, placebo-controlled trial of UDCA
treatment and in whom liver biopsy specimens obtained at entry were reassessed.
Relationships between histological features, fatigue, pruritus and biochemistries
were calculated by using exact tests for 2 ordinal variables. RESULTS: The
degrees of severity of fatigue and pruritus were significantly and exclusively
related to the presence of florid interlobular bile duct lesions (p<0.01 and
p<0.02, respectively). The only laboratory parameter associated with the presence
of interlobular bile duct florid lesion was IgM level. The most discriminant
biochemical test for interlobular bile duct paucity was gamma
glutamyltranspeptidase activity. The degree of severity of both lymphocytic
hepatocellular piecemeal necrosis and lobular inflammation and necrosis was
mainly associated with increased gammaglobulin and IgG levels and to a lesser
extent with increased IgM and aspartate aminotransferase levels. The extent of
fibrosis was mainly associated with gammaglobulin levels and to a lesser degree
with serum albumin, bilirubin and IgG levels. CONCLUSIONS: Symptoms and
biochemistries classically used to assess primary biliary cirrhosis reflect in
part the degree of severity of the main elementary histological lesions. We
propose that the picture of primary biliary cirrhosis results from the clinical
and biochemical expression of three distinct processes, e.g., bile duct
inflammation and destruction, parenchymal inflammation and necrosis, and
fibrosis. The various combinations of these processes may explain why the
spectrum of primary biliary cirrhosis varies from typical primary biliary
cirrhosis to mixed type of primary biliary cirrhosis and autoimmune hepatitis and
suggests that the response to therapies may depend on the predominance of each
process in a given patient.
PMID- 10190723
TI - Reversible Kupffer cell suppression in biliary obstruction is caused by
hydrophobic bile acids.
AB - BACKGROUND/AIM: Biliary obstruction is associated with suppressed Kupffer cell
clearance of bacteria and intracellular bactericidal activity of the phagocytes.
We studied the superoxide generation of Kupffer cell in biliary obstruction and
after incubation with bile acids to elucidate the mechanism of impaired
intracellular killing of these phagocytes. METHODS: Kupffer cells were extracted
from rats with common bile duct ligation or sham-operation. The extracted cells
were tested for superoxide production immediately after extraction, 2 h and 24 h
post-extraction. Superoxide generation from Kupffer cells after incubation with
five bile acids (cholic acid, taurocholic acid, deoxycholic acid,
chenodeoxycholic acid and ursodeoxycholic acid) at two different concentrations
(0.1 mM and 1.0 mM) were also studied. Cell viability was monitored by trypan
blue exclusion. RESULTS: Kupffer cells extracted from common duct-ligated animals
had significantly lower superoxide production (-1.37+/-0.24 nmol O2(-)/10(6)
cells) compared to that from sham-operated rats (2.54+/-0.58 nmol O2(-)/10(6)
cells) and non-operated rats (2.15+/-0.76 nmol O2(-)/10(6) cells) (p<0.05). After
2 h of resting in culture medium, these cells recovered significantly in
superoxide production to 2.72+/-0.63 nmol O2(-)/10(6) cells (p<0.01). A dose
related reduction in superoxide production was demonstrated when Kupffer cells
were incubated with bile acids. Hydrophobic bile acids (deoxycholic acid and
chenodeoxycholic acid) caused more significant suppression than with hydrophilic
bile acids (cholic acid, taurocholic acid, ursodeoxycholic acid). The drop in
superoxide production after bile acid treatment was not due to cell death.
Washing in Hank's balanced salt solution resulted in partial recovery of Kupffer
cell superoxide production. CONCLUSION: High blood levels of hydrophobic bile
acids are likely to be the cause of impaired intracellular bactericidal activity
of Kupffer cells in biliary obstruction.
PMID- 10190724
TI - Expression of matrix metalloproteinase-13 and tissue inhibitor of
metalloproteinase-1 in acute liver injury.
AB - BACKGROUND/AIMS: Matrix metalloproteinase-13, one of the principal neutral
proteinases capable of cleaving native fibrillar collagens, is important in the
degradation and remodeling of extracellular matrix. However, its precise
expression in liver injury has not been characterized. We examined the kinetics
of the expression of matrix metalloproteinase-13 and one of its specific
inhibitors, tissue inhibitor of metalloproteinase-1, in acute liver injury in
rats. METHODS: Acute liver injury was induced by administration of carbon
tetrachloride or two different doses of D-galactosamine hydrochloride in Wistar
rats. Hepatic matrix metalloproteinase-13 and tissue inhibitor of
metalloproteinase-1 mRNA levels were then examined by Northern blotting. RESULTS:
All rats survived after liver injury induced by carbon tetrachloride or low doses
of D-galactosamine hydrochloride. However, rats died 5 days after induction of
liver injury by high doses of D-galactosamine hydrochloride. In carbon
tetrachloride-induced liver injury, matrix metalloproteinase-13 mRNA was
transiently increased between 6 h and 1 day after injury. Tissue inhibitor of
metalloproteinase-1 mRNA expression was increased between 6 h and 3 days after
the peak of matrix metalloproteinase-13 expression. Similar patterns of matrix
metalloproteinase-13 and tissue inhibitor of metalloproteinase-1 expression were
observed in low-dose D-galactosamine hydrochloride-induced liver injury. In
contrast, in high-dose D-galactosamine hydrochloride-induced liver injury, tissue
inhibitor of metalloproteinase-1 expression peaked before matrix
metalloproteinase-13 expression, which was increased 2 days after injury. Both
mRNA levels continued to increase until death. CONCLUSIONS: Transient expression
of matrix metalloproteinase-13, followed by that of tissue inhibitor of
metalloproteinase-1, was observed during recovery from acute liver injury induced
by carbon tetrachloride and low-dose D-galactosamine hydrochloride. In contrast,
disordered expression of matrix metalloproteinase-13 was observed in fatal liver
injury caused by high-dose D-galactosamine hydrochloride. These results indicate
that matrix metalloproteinase13 plays an important role in the early phase of
recovery from liver injury.
PMID- 10190725
TI - Spatial distribution of tissue inhibitor of metalloproteinase-1 mRNA in chronic
liver disease.
AB - BACKGROUND/AIMS: Tissue inhibitor of metalloproteinase-1, a specific inhibitor of
matrix metalloproteinases, plays an important role in the pathogenesis of
fibrosis and tumor progression. However, the precise expression of tissue
inhibitor of metalloproteinase-1 messenger RNA in human hepatic fibrosis has not
yet been defined. We investigated the spatial distribution of tissue inhibitor of
metalloproteinase-1 messenger RNA in chronic human liver disease. METHODS:
Northern and in situ hybridization of probes to tissue inhibitor of
metalloproteinase-1 messenger RNA were performed in specimens from 16 surgically
resected human livers. Immunohistochemical staining of sections for tissue
inhibitor of metalloproteinase-1 and immunoelectron microscopy were also
performed. RESULTS: Northern hybridization demonstrated that expression of tissue
inhibitor of metalloproteinase-1 messenger RNA was increased 3.9-fold in mild
chronic hepatitis, 6.8-fold in moderate chronic hepatitis, and 6.4-fold in
cirrhosis, compared with control liver. In situ hybridization showed the
expression of tissue inhibitor of metalloproteinase-1 messenger RNA in spindle
shaped cells in the fibrous septa and lobules in chronic hepatitis and cirrhosis;
these cells were immunohistochemically positive for a-smooth muscle actin.
Immunoelectron microscopy revealed localization of tissue inhibitor of
metalloproteinase-1 in between fibers, to the rough endoplasmic reticula of
stellate cells located in the lobules and periportal areas, and to fibroblasts in
the fibrous septa. These results indicate that tissue inhibitor of
metalloproteinase-1 was produced mainly by stellate cells in the specimens of
chronic liver diseases. CONCLUSIONS: Expression of tissue inhibitor of
metalloproteinase-1 messenger RNA is increased in hepatic fibrosis and stellate
cells are involved primarily in its expression.
PMID- 10190726
TI - Centrilobular and perisinusoidal fibrosis in experimental congestive liver in the
rat.
AB - BACKGROUND/AIMS: The pathogenesis of congestive hepatic fibrosis is known to be a
reaction of hepatic stromal cells following prolonged congestive heart failure or
hepatic outflow obstruction. However, little is known about the fibrotic process
itself. This study documents the hepatic morphology and ultrastructure of the
fibrotic processes in an experimental model of congestive hepatic fibrosis in
rats. METHODS: In this model we ligated the abdominal portion of the inferior
vena cava in the space between the diaphragm and liver, and observed liver
morphology 24 h, 1 week and 6 weeks after the operation. The cytoskeletal
components of the hepatic stellate cells and myofibroblasts were identified by
immunohistochemistry for glial fibrillary acidic protein (GFAP) and a-smooth
muscle actin (a-SM actin). Extracellular matrices of reticulin fibers and
fibronectin were localized using silver impregnation and immunohistochemical
staining. RESULTS: Soon after ligation of the vena cava, foci of cells at
variable stages of necrosis appeared in the centrilobular areas, the
topographical localization of which was highly variable within the liver. The
fibrotic processes were subclassified into three stages. In the first stage (24 h
after ligation), abundant neutrophils, macrophages and GFAP-positive stellate
cells appeared, but a-SM actin-positive cells were not detected in the necrotic
areas. In the second stage (1 week after ligation), the GFAP-positive cells
disappeared, but a-SM actin-positive myofibroblasts appeared. In the third stage
(6 weeks after ligation), a large number of a-SM actin-positive myofibroblasts
were observed, and there was heavy deposition of connective tissue proteins, such
as reticulin fibers and fibronectin, in centrilobular areas. Two interesting
observations were that: (1) the distribution of centrilobular necrosis was highly
variable within the liver, and (2) the fibrosis was confined to focal
centrilobular areas involving the perivenular sinusoidal area without periportal
fibrosis. CONCLUSIONS: These findings suggest that GFAP-positive stellate cells
are transformed into a-SM actin-positive myofibroblasts, and these myofibroblasts
produce extracellular matrix proteins in centrilobular sinusoidal areas under
congestive conditions.
PMID- 10190727
TI - Down-regulation of endothelin receptors by transforming growth factor beta1 in
hepatic stellate cells.
AB - BACKGROUND/AIMS: Hepatic endothelin-1 (ET-1) receptor density as well as the
levels of both ET-1 and transforming growth factor beta1 (TGF-beta1) increase in
liver cirrhosis. Considering their potent contractile (ET-1) and fibrogenic (TGF
beta1) actions on myofibroblastic stellate cells found in the fibrotic/cirrhotic
liver, we aimed to investigate the effects of TGF-beta1 on ET-1 receptors and ET
1 synthesis in these cells. METHODS: Stellate cells isolated from rat liver by
enzymatic digestion were cultured and subjected to TGF-beta1 treatment. Cellular
ET-1 receptors and ET-1 released in the medium were determined. RESULTS: TGF
beta1 treatment produced time- and dose-dependent decrease in ET-1 binding sites,
but did not affect the affinity of the receptors for ET-1. TGF-beta1 also
stimulated the release of ET-1 from stellate cells. The extent of TGF-beta1
induced inhibition of [125I]ET-1 binding was much greater for ETB subtype (73+/
18% inhibition), which comprised a major portion (78+/-12%) of the total ET-1
receptors, than for ETA subtype (35+/-11% inhibition). The mRNA expression of the
ET-1 receptors also was reduced by TGF-beta1 treatment. TGF-beta1-induced
reduction in ET-1 receptor density was coupled to the inhibition of ET-1
stimulated release of [3Hlarachidonic acid from the prelabeled cells. The effects
of TGF-beta1 were inhibited by a TGF-beta1 neutralizing monoclonal antibody.
CONCLUSIONS: These results suggest that the TGF-beta1-induced decrease in ET-1
receptor density may be an important mechanism in limiting the pathologic actions
of ET-1 on stellate cells in chronic liver disease.
PMID- 10190728
TI - Von Willebrand factor could be an index of endothelial dysfunction in patients
with cirrhosis: relationship to degree of liver failure and nitric oxide levels.
AB - BACKGROUND/AIMS: The aim of this study was to evaluate the relationship between
plasma levels of von Willebrand factor (vWF), a marker of endothelial cell
activation, and nitric oxide, a powerful vasodilator synthesized by endothelial
cells, in 27 patients with cirrhosis at different stages of the disease. These
results were compared with those of age-matched normal, healthy subjects (n=10).
METHODS: vWF:antigen was measured by electro-immunodiffusion test and serum
nitrite and nitrate levels, the stable end products of nitric oxide metabolism,
were determined by an enzymatic procedure. RESULTS: vWF:antigen and
nitrite/nitrate levels were significantly higher in cirrhotic patients (367+/
185% and 29.3+/-10.8 micromol/l) than in healthy subjects (92+/-20% and 19.2+/
8.3 micromol/l, p<0.05, respectively). Higher levels of vWF:antigen and
nitrites/nitrates were observed in patients with more advanced degrees of liver
failure, as reflected by quantitative Child-Pugh's score (516+/-154% and 38.3+/
7.8 micromol/l in Child-Pugh > or = 9 vs 227+/-61% and 21.0+/-6.1 micromol/l in
Child-Pugh <9, p<0.001, respectively). Moreover, both endothelial-related factors
were higher in patients with ascites than those without ascites (543+/-158% and
37.8+/-8.9 micromol/l vs 262+/-103% and 24.4+/-8.8 micromol/l, p<0.001,
respectively). In the overall series, a highly significant linear correlation
between nitrites/nitrates and vWF:antigen levels was observed in patients with
cirrhosis (r=0.79, p<0.001). CONCLUSIONS: These results support a cirrhosis
related endothelial dysfunction and suggest that plasma vWF measurement could be
useful as a marker of endothelial disturbance in patients with cirrhosis.
PMID- 10190729
TI - Prolonged bleeding time in experimental cirrhosis: role of nitric oxide.
AB - BACKGROUND/AIMS: Nitric oxide is a powerful in vitro inhibitor of platelet
adhesion and aggregation. Our aim was to investigate whether the in vivo
inhibition of nitric oxide release shortens bleeding time, in rats with cirrhosis
induced by chronic bile duct ligation. METHODS: Mean arterial pressure and
bleeding time were measured under basal conditions and 5, 15 and 30 min after
administration of vehicle (0.9% saline) or an inhibitor of nitric oxide
synthesis, Nw-nitro-L-arginine (5 mg/kg, iv). Mean arterial pressure was measured
with an intra-arterial catheter and bleeding time with a standardized Simplate
device. RESULTS: Cirrhotic rats showed a lower mean arterial pressure (116+/-4
mmHg) and a prolonged bleeding time (177+/-40 s) compared to control animals
(133+/-6 mmHg and 95+/-12 s, respectively, p<0.01). In cirrhotic rats, Nw-nitro-L
arginine significantly increased mean arterial pressure (from 116+/-5 to 141+/-11
mmHg, p<0.05) and completely normalized bleeding time (from 170+/-39 to 103+/-21
s, p<0.05) 15 min after administration. Pretreatment with L-arginine (300 mg/kg,
iv) prevented the hemodynamic and hemostatic changes induced by Nw-nitro-L
arginine. A trend to normalize platelet adhesion was observed in cirrhotic rats
after the inhibition of nitric oxide production. In control animals, Nw-nitro-L
arginine increased mean arterial pressure, while no effect on bleeding time was
observed. CONCLUSIONS: These findings support the concept that nitric oxide may
be a mediator in the bleeding time abnormalities associated with experimental
cirrhosis.
PMID- 10190730
TI - Hepatocyte proliferative activity in human liver cirrhosis.
AB - BACKGROUND/AIMS: The objective of this study was to validate, with an independent
prospective cohort of patients, our previous data indicating that the
proliferating cell nuclear antigen-labeling index (PCNA-LI) reflects the liver
functional reserve in human cirrhosis and might have prognostic significance for
patient survival. We also examined how this proliferative index is related to the
expression of transforming growth factor beta1 (TGFbeta1) as a possible correlate
of hepatocyte proliferative activity. METHODS: The present group (n=70 patients)
was similar in composition to our previous group regarding age, sex and severity
of liver cirrhosis. PCNA and TGFbeta1 immunostaining were analyzed on methanol
fixed, paraffin-embedded liver biopsies. RESULTS: Our data show that PCNA-LI
declined significantly with worsening Child class and was negatively correlated
with the Pugh score. Twenty-five patients died and 10 underwent liver
transplantation during the observation period. Liver function, hepatic venous
pressure gradient and hepatocyte PCNA-LI were significantly different in
survivors and non-survivors. At a mean follow-up of 356 days, the patients with a
PCNA-LI higher than 4.4% (the previously determined best cut-off value) had a
significantly higher probability of survival than those with a PCNA-LI < or =
4.4% (0.87 vs 0.48, p=0.0009). TGFbeta1 expression in liver parenchyma correlated
negatively with PCNA-LI, suggesting that this cytokine could be involved in the
impaired regeneration observed in worsened liver cirrhosis. CONCLUSIONS: This
prospective study strengthens our previous observation that, in cirrhosis,
hepatocyte proliferative activity, as evaluated by the PCNA-LI, provides
information on liver functional reserve as well as on the patient's prognosis.
PMID- 10190731
TI - Ultrasonographic diagnosis of hepatic fibrosis or cirrhosis.
AB - BACKGROUND/AIMS: Evaluation of the degree of hepatic fibrosis is especially
important in patients with chronic liver disease. Our aim was to study the
diagnostic accuracy of abdominal ultrasonography for cirrhosis or fibrosis.
METHODS: Twenty-three clinical (n=12) and Doppler ultrasonic (n=11) variables
were recorded in 243 patients with chronic (alcoholic and viral) liver disease
under conditions close to those of clinical practice. Fibrosis was classified
into six grades by two pathologists. Diagnostic accuracy was evaluated by
discriminant analysis, first globally using all variables, then by stepwise
analysis. RESULTS: A) Diagnosis of cirrhosis: 1) whole group (n=243): diagnostic
accuracy was globally 84%, and 84% with two variables: spleen length, portal
velocity; 2) compensated chronic liver disease (n=191): diagnostic accuracy was
globally 85%, and 82% with two variables: liver surface, liver length (right
kidney); 3) alcoholic compensated chronic liver disease (n=109): diagnostic
accuracy was globally 86%, and 88% with two variables: spleen length, liver
length (middle clavicle); 4) viral compensated chronic liver disease (n= 83):
diagnostic accuracy was globally 86% and 86% with one variable: liver surface. By
subtracting the proportion of patients who could not be investigated due to
anatomical limitations, the highest calculated univariate diagnostic accuracy
decreased by 7%. B) Diagnosis of fibrosis: diagnostic accuracy was globally 84%
for extensive fibrosis. CONCLUSIONS: Cirrhosis can be correctly diagnosed in 82
88% of patients with chronic liver disease using a few ultrasonographic signs.
However, the diagnostic accuracy of ultrasound is decreased by the anatomical
limitations of this technique.
PMID- 10190732
TI - Acute and chronic haemodynamic and renal effects of carvedilol in patients with
cirrhosis.
AB - BACKGROUND/AIMS: Recent reports have suggested that the vasodilating beta-blocker
carvedilol may have beneficial acute haemodynamic effects in cirrhotic portal
hypertension. However, no data exist on chronic use or renal effects in this
patient group. The aim of this study was to assess the acute and chronic
haemodynamic and renal effects of carvedilol in cirrhotic patients. METHODS:
Seventeen cirrhotic patients (mean age 55.2+/-2.8, mean Child-Pugh score 7.4+/
0.5) were studied. Hepatic venous pressure gradient, cardiac output, systemic
vascular resistance, mean arterial pressure, heart rate and hepatic blood flow
were measured before and 1 h after 25 mg carvedilol. After 4 weeks of therapy
with carvedilol 25 mg daily, these measurements were repeated before and after
rechallenge with carvedilol. Urine volume, sodium excretion and creatinine
clearance were also measured before and after 4 weeks of therapy. RESULTS: Seven
patients did not complete the 4-week carvedilol therapy due to hypotension or
poor compliance. Hepatic venous pressure gradient fell by 20.8% acutely (p<0.001)
and by 16.3% after 4 weeks of therapy (p<0.002). Heart rate, mean arterial
pressure and cardiac output fell after acute administration of carvedilol, but
only heart rate fell significantly after 4 weeks of treatment. Hepatic blood
flow, urine volume, sodium excretion and creatinine clearance remained unchanged
after therapy. CONCLUSION: Carvedilol has beneficial effects on splanchnic
haemodynamics following acute and chronic administration in cirrhosis, without
compromising hepatic blood flow or renal function. However, a substantial number
of patients cannot tolerate 25 mg daily.
PMID- 10190733
TI - Differential effects of jaundice and cirrhosis on beta-adrenoceptor signaling in
three rat models of cirrhotic cardiomyopathy.
AB - BACKGROUND/AIMS: Attenuated cardiac function has been reported in cirrhosis as
well as in jaundice, but the mechanisms remain unclear. This study aimed to
explore the differential effects of jaundice and cirrhosis on the heart. METHODS:
Three rat models of cirrhosis were studied: chronic bile duct ligation, bile duct
ligation followed by choledochojejunostomy to relieve jaundice, and a less
jaundiced model induced by thioacetamide administration. Controls underwent a
sham operation. Cardiac function was assessed by measuring isolated ventricular
papillary muscle contractility. Cardiac beta-adrenergic receptor signaling was
studied by measuring cAMP production stimulated at the receptor, G-protein, and
adenylyl cyclase levels in the signaling pathway, using isoproterenol, aluminum
fluoride and forskolin, respectively. RESULTS: Serum bilirubin and bile salt
levels were markedly elevated in the bile duct-ligated group, moderately
increased in the thioacetamide rats, and normal in the choledochojejunostomy and
sham-operated controls. Papillary muscle contractile force after maximal beta
adrenergic receptor stimulation was decreased to a similar extent in all three
cirrhotic models. In the bile duct-ligated and thioacetamide-induced cirrhotic
rats, production of cAMP by all three drugs was significantly attenuated.
However, the cAMP production in the choledochojejunostomy group was blunted only
with isoproterenol and fluoride, and remained intact with forskolin stimulation.
CONCLUSIONS: These results demonstrate that cirrhosis per se impairs cardiac
function by attenuating the portion of the beta-adrenergic receptor signaling
pathway upstream of adenylyl cyclase. Furthermore, significant jaundice and/or
cholemia can inhibit adenylyl cyclase, which may contribute to blunted cardiac
contractility in jaundiced patients.
PMID- 10190734
TI - Altered transmembrane ionic flux in hepatocytes isolated from cirrhotic rats.
AB - BACKGROUND/AIMS: Although cirrhosis is known to be associated with many
hepatocyte abnormalities, there is no well-established model to study the
cellular drug uptake process independent of hemodynamic effects. The purpose of
the present study was to test the following hypothesis: hepatocytes isolated from
cirrhotic animals may be used as a model to study the cellular abnormalities
associated with cirrhosis. Our hypothesis was tested by comparing the membrane
potential (PD) of hepatocytes in anesthetized healthy and cirrhotic animals, and
the PD and [3H]palmitic acid clearance rate of hepatocytes isolated from healthy
and cirrhotic animals. METHODS: Mild to moderate cirrhosis was induced in female
Sprague-Dawley rats by CCl4 administration. PD was recorded in anesthetized
animals using intracellular microelectrodes. Hepatocytes from those livers were
subsequently isolated by collagenase perfusion for further determinations of PD
and [3H]palmitic acid uptake. RESULTS: The mean (+/-SEM) hepatocyte PD from
intact rat livers was 38+/-1 mV (control) and -32+/-1 mV (cirrhosis; n=6/group,
p<0.01). The PD (mean+/-SEM) in isolated hepatocytes was -21+/-1 mV (control) and
-15+/-1 mV (cirrhosis, n=13/group, p<0.01). The clearance rate of [3H]palmitic
acid was lower in hepatocytes isolated from cirrhotic animals (26%) than in those
isolated from healthy control animals (p<0.01). CONCLUSION: The results of this
study indicate that hepatocytes isolated from cirrhotic animals may be used to
study the cellular abnormalities associated with cirrhosis.
PMID- 10190735
TI - Effect of cirrhosis on sulphation by the isolated perfused rat liver.
AB - BACKGROUND/AIMS: There is evidence to suggest that not all pathways of drug
metabolism are similarly affected in cirrhosis. The effect of cirrhosis on drug
oxidation and glucuronidation has been extensively investigated but little is
known of the effect of cirrhosis on drug sulphation. The aim of this study was to
investigate the effect of cirrhosis on sulphation. METHODS: We investigated the
effect of cirrhosis on p-nitrophenol sulphation and compared this with the effect
of cirrhosis on p-nitrophenol glucuronidation as well as on d-propranolol
oxidation simultaneously in the single-pass isolated perfused rat liver. The
perfusate contained added inorganic sulphate to maximise production of p
nitrophenol sulphate. RESULTS: About 77% and 59% of p-nitrophenol was eliminated
as the sulphate conjugate by the healthy (n=6) and cirrhotic (n=7) livers,
respectively. Mean total p-nitrophenol clearance was decreased in cirrhosis
(healthy: 18.5+/-0.2 vs. cirrhotic 15.3+/-4.0 ml/min; p<0.05). The decrease in
total clearance of p-nitrophenol was due solely to the decrease in sulphate
formation clearance, which was significantly decreased (healthy: 14.1+/-1.9 vs.
cirrhotic: 9.27+/-3.33 ml/min; p<0.05). Mean glucuronide formation clearance
(healthy: 5.11+/-0.94 vs cirrhotic: 5.79+/-0.85 ml/ min; p>0.05) was not
significantly altered. Mean total propranolol clearance was decreased in
cirrhosis (healthy: 19.9+/-0.1 vs. cirrhotics: 18.0+/-1.5 ml/min; p<0.05).
CONCLUSIONS: We have shown that in cirrhosis there is significant impairment of
drug oxidation and sulphation, whilst glucuronidation is spared. The decreased
sulphation of p-nitrophenol was most likely due to a decrease in phenol
sulphotransferase and/or decrease in cofactor synthesis.
PMID- 10190736
TI - Splanchnic haemodynamics after intravenous terlipressin in anaesthetised healthy
pigs.
AB - BACKGROUND/AIMS: Terlipressin is used for the treatment of bleeding oesophageal
varices. We evaluated the effects of terlipressin on hepatic haemodynamics, with
special focus on the interactions between portal venous flow and hepatic arterial
flow over time. Secondly, we evaluated the estimated hepatic blood flow by the
ICG clearance method against direct measurements of hepatic blood flow. METHODS:
Eight healthy anaesthetised pigs received terlipressin 1 mg or placebo
intravenously in a randomised, blind, cross-over design. Hepatic arterial flow,
portal venous flow, systemic haemodynamics, and portal vein diameter were
recorded simultaneously. Portal venous flow and hepatic arterial flow were
measured by transit time ultrasound flowmetry. Estimated hepatic blood flows at
baseline and after terlipressin were compared with the sum of the portal venous
flow and hepatic arterial flow. RESULTS: Portal venous flow decreased
significantly 5 min after administration of terlipressin (p<0.05). At 30 min it
had decreased by 34% (p<0.01) and the hepatic arterial flow had increased by 81%
(p<0.01). The estimated hepatic blood flow and the hepatic blood flow decreased
by 23% (p<0.015). At baseline the estimated hepatic blood flow and the hepatic
blood flow correlated significantly (r=0.85, p<0.01), but this correlation
disappeared after administration of terlipressin (r=0.06, p=ns). The hepatic
blood flow was 12% higher than the estimated hepatic blood flow before and after
terlipressin. CONCLUSIONS: Terlipressin decreased the portal venous flow, hepatic
blood flow, and estimated hepatic blood flow significantly and was accompanied by
a substantial increase in hepatic arterial flow. The estimated hepatic blood flow
and hepatic blood flow were strongly correlated at baseline, but after
terlipressin the correlation disappeared.
PMID- 10190737
TI - Direct evidence that hepatocyte growth factor-induced invasion of hepatocellular
carcinoma cells is mediated by urokinase.
AB - BACKGROUND/AIMS: We have shown that hepatocyte growth factor secreted by human
hepatic myofibroblasts increased the in vitro invasion of the hepatocarcinoma
cell line HepG2 through Matrigel. Our aim in this study was to evaluate the role
of urokinase in this process. METHODS: Expression of urokinase in HepG2 cells was
measured by Northern blot and zymography, and plasminogen activation was shown by
a chromogenic substrate assay. Cell invasion was assayed on Matrigel-coated
filters. Urokinase and urokinase receptor transcripts in hepatocarcinoma were
detected by reverse transcription-polymerase chain reaction. Activated hepatocyte
growth factor was detected by Western blot with a hepatocyte growth factor-beta
chain-specific antibody. RESULTS: HepG2 cells expressed urokinase mRNA and
secreted active urokinase. Urokinase expression was enhanced by hepatocyte growth
factor at the protein and mRNA level. Notably, cell-surface-associated urokinase
was increased 22-fold by hepatocyte growth factor. Hepatocyte growth factor also
increased urokinase receptor mRNA expression. B428, a urokinase inhibitor,
decreased by up to 70% HepG2 invasion induced by myofibroblasts and by 90% that
induced by recombinant hepatocyte growth factor. This was not due to a decrease
in the generation of activated hepatocyte growth factor by myofibroblasts.
Finally, all 17 hepatocarcinoma samples tested expressed urokinase and urokinase
receptor transcripts. CONCLUSION: Hepatocyte growth factor-dependent,
myofibroblasts-induced invasion of HepG2 cells is secondary to the induction of
urokinase expression on tumor cells.
PMID- 10190738
TI - Expression and processing of gastrin in hepatocellular carcinoma, fibrolamellar
carcinoma and cholangiocarcinoma.
AB - BACKGROUND/AIMS: Gastrin is a trophic factor within the normal gastrointestinal
tract and is also a mitogen for a number of gastrointestinal and non
gastrointestinal tumours. Precursor forms of gastrin including progastrin (proG)
and glycine-extended gastrin (G-gly) as well as the fully processed amidated
gastrin (G-NH2) are expressed by tumours. There has been little study of the role
of gastrin in either normal liver or liver tumours. The aim of this study was to
identify the expression of CCK-B/gastrin receptor (CCK-BR), proG, G-gly and G-NH2
in normal liver and liver tumours. METHODS: Tissue sections from patients with
hepatocellular carcinoma, fibrolamellar carcinoma, cholangiocarcinoma as well as
normal liver biopsies were assessed for expression of CCK-BR and gastrin
isoforms. RESULTS: Most liver tumours express CCK-BR and are able to process
gastrin as far as proG and G-gly, although not as far as the amidated form. There
appears to be little expression of the receptor and no expression of precursor
forms of gastrin in normal liver. CONCLUSIONS: Liver tumours express the CCK-BR
and precursor forms of gastrin. This expression may be associated with tumour
proliferation.
PMID- 10190739
TI - Acute hepatitis after riluzole administration.
AB - Riluzole is a new drug representing the first active treatment for amyotrophic
lateral sclerosis. We report the cases of two patients who developed acute
hepatitis after taking riluzole at the recommended dose (100 mg daily) for 7 and
4 weeks, respectively. In both cases, liver histology showed hepatocellular
damage with inflammatory infiltration and microvesicular steatosis without
fibrosis. Liver enzymes returned to normal 4 and 8 weeks, respectively, after
riluzole withdrawal. In one case, the readministration of riluzole was followed
by the relapse of hepatitis. These two observations strongly suggest that
riluzole can induce acute hepatitis with associated hepatocellular damage and
microvesicular steatosis. They also suggest that liver enzymes should be
monitored during treatment with riluzole.
PMID- 10190740
TI - Images in hepatology. Steatosis hepatis in celiac disease.
PMID- 10190741
TI - Complications of cirrhosis: is endothelium guilty?
PMID- 10190742
TI - Antiviral chemotherapy for chronic hepatitis B infection: lessons learned from
treating HIV-infected patients.
PMID- 10190743
TI - Lamivudine is safe and effective in fulminant hepatitis B.
PMID- 10190744
TI - Prevalence of transmitted transfusion virus (TTV) in populations at different
risk for hepatitis virus: hemodialysis, chronic hepatitis C and cryptogenetic
hepatitis patients.
PMID- 10190745
TI - Cinnarizine-induced cholestasis.
PMID- 10190746
TI - Sodium, potassium, chloride and calcium concentrations measured in pigeon
perilymph and endolymph.
AB - According to Davis' (1965) model of the inner ear, a potential difference between
the endocochlear potential and the hair cell resting potential drives the
transduction current across the apical hair cell membrane. It is assumed that the
endocochlear potential (EP) consists of two components. The first is a diffusion
potential, which depends on the ionic composition of endolymph and perilymph and
on the permeability of the perilymph-endolymph barrier. The second is an
electrogenic component which is determined by active ion transport across the
perilymph-endolymph barrier. In birds, the EP is between +8 and +20 mV. Little is
known about the underlying mechanisms responsible for the measured EP in birds.
The present paper studies whether ionic compositions of endo- and perilymph might
explain the EP in birds. Concentrations of Na+, K+, Ca2+ and Cl- in pigeon scala
vestibuli, scala tympani and scala media were determined with ion-selective
microelectrodes. Na+, K+, Ca2+ and Cl- were 150.0, 4.2, 1.4 and 117.0 mM in
perilymph (scala tympani and scala vestibuli). In scala media, the concentrations
of K+, Ca2+ and Cl- were 140.6, 0.23 and 142.1 mM.
PMID- 10190747
TI - Organization and connections of the dorsal descending nucleus and other presumed
acoustic areas in the brainstem of the teleost fish, Astronotus ocellatus.
AB - This study provides new information on brainstem areas, assumed to be auditory
based on observations in other species, in the oscar, Astronotus ocellatus. The
primary goal of the study was to explore the morphology of the dorsal descending
octaval nucleus, which contains a population of neurons that receives acoustic
afferents from the inner ear. Using cytoarchitectonic and connectional criteria,
we revised the previously defined dorsal boundary of the descending octaval
nucleus, such that the most dorsomedial neurons in this nucleus are positioned
ventral to the cerebellar crest and medial to nucleus medialis. At some levels,
these dorsomedial cells are continuous with another part of the dorsal descending
nucleus that underlies nucleus medialis. The terminal fields of the saccule and
lagena are located within this latter, more ventral part of the dorsal descending
nucleus. However, the dorsomedial cells that are proximate to the cerebellar
crest have long ventral dendrites that extend into these terminal fields, and
therefore likely receive saccular and lagenar input. In contrast to a previous
report, saccular afferents terminate more medially within the dorsal descending
nucleus than do lagenar inputs. Injections of horseradish peroxidase in nucleus
centralis of the torus semicircularis revealed that many descending nucleus
neurons that lie within the saccular and lagenar terminal fields, including the
dorsomedial neurons proximate to the cerebellar crest, project to this acoustic
midbrain area. These injections also revealed a secondary octaval population like
that described in otophysan fishes.
PMID- 10190748
TI - Some effects of background noise on modulation detection interference.
AB - Modulation thresholds were obtained for a 2000-Hz signal carrier modulated at a
rate of 10 Hz. Thresholds were obtained without a masker carrier and in the
presence of a masker carrier that was either unmodulated or modulated at a rate
of 10 Hz and a depth of 100% (m(m) = 1.0). Of primary interest was whether the
amount of interference caused by the masker was influenced by the frequency
proximity of the masker to the signal, and whether background noise had an
influence on that proximity effect. In general, for masker carriers higher in
frequency than the 2000-Hz signal carrier, there was a tendency for the
interference to decline as the masker was moved farther away from the signal for
masker carriers lower than 2000 Hz, there was little or no proximity effect.
Broadband noise eliminated the proximity effect obtained with an unmodulated
masker, but not that obtained with a modulated masker. Results with a narrowband
noise suggest that the broadband noise has its effect by masking the high
frequency side of the signal's excitation pattern. These results, as well as the
results of an excitation pattern analysis, suggest that the proximity effect with
all unmodulated masker may be mediated via a peripheral, within-channel
interaction, whereas that with a modulated masker may be mediated via a central,
across-channel interaction.
PMID- 10190749
TI - Development of blood-labyrinth barrier in the semicircular canal ampulla of the
rat.
AB - Cationic polyethyleneimine (PEI) administered intravenously was transported to
anionic sites on the capillary and subepithelial basal laminae (BL) in the
vestibular labyrinth. Therefore, changes in the PEI distribution on the BL
reflect changes in the transport system in the vestibular labyrinth. A 0.1% PEI
solution was administered intravenously (7.5 ml/kg) to developing (1, 4, 7, 14
days after birth) and adult rats in order to investigate the development of the
macromolecular transport in the ampulla of the semicircular canal as a function
of age. After 1 h, the bony labyrinth was removed and embedded in Epoxy resin.
Ultrathin sections of the ampulla were then examined with a transmission electron
microscope. In the subepithelial BL in the dark cell area and capillary BL in the
crista ampullaris, the PEI distribution in both 1- and 4-day-old rats was
markedly increased compared to that in either 7-, 14-day or adult rats. In the
sensory cells in 1-, 4-day or 7-day-old rats, PEI density and area was
significantly greater than in the adult rats. These findings suggest that the
macromolecular transport system in the developing rat ampulla becomes mature by
14 days after birth and that the maturation of its transport system in the
ampulla is strongly associated with that in the stria vascularis.
PMID- 10190750
TI - Ultrastructure and immunohistochemical identification of the extracellular matrix
of the chinchilla cochlea.
AB - The molecular composition and three-dimensional organization of the extracellular
matrix (ECM) was studied by immunofluorescent microscopy, transmission and
scanning electron microscopy in three connective tissue structures of the
cochlea: the spiral limbus, basilar membrane and spiral ligament. Type II
collagen, fibronectin, tenascin, chondroitin sulfate proteoglycans, alphav and
beta1 integrins were immunolocalized in the ECM of these connective tissue
structures. Electron micrographs showed a continuum of cross-striated collagen
fibrils having a similar diameter and axial periodicity that spread from the
spiral limbus via the basilar membrane and into the spiral ligament. Some of
collagen fibrils were aggregated laterally into bundles. Bundle images, and their
digital Fourier transformations, showed a major 67-nm axial D-repeat
characteristic for collagen fibrils. Transmission electron microscopy showed
numerous proteoglycans associated with the collagen fibrils. The spiral limbus,
basilar membrane and spiral ligament demonstrated regional differences in
molecular composition and structural organization of their ECM. The glycoproteins
fibronectin, tenascin and alphav integrin were immunolocalized mainly in the
basilar membrane. Collagen fibrils of the spiral limbus and spiral ligament did
not appear to be strongly oriented. However, most of the collagen fibrils in the
basilar membrane were arranged into radially directed bundles. Collagen fibrils
in the basilar membrane were also surrounded by a homogeneous matrix, which was
immunoreactive to fibronectin and tenascin antibodies. A more complete
understanding of the composition and structural organization of the ECM in these
connective tissue structures in the cochlea provides a foundation upon which
micromechanical models of cochlear function can be constructed.
PMID- 10190751
TI - KHRI-3 monoclonal antibody-induced damage to the inner ear: antibody staining of
nascent scars.
AB - Intracochlear infusion of the KHRI-3 monoclonal antibody results in in vivo
binding to guinea pig inner ear supporting cells, loss of hair cells and hearing
loss. To further characterize the basis for KHRI-3-induced hearing loss, antibody
was produced in a bioreactor in serum-free medium, affinity purified, and
compared to conventionally prepared antibody by infusion into the scala tympani
using mini-osmotic pumps. In vivo antibody binding was observed in 10 of 11
guinea pigs. A previously unreported pattern of KHRI-3 antibody binding to cells
involved in scar formation was noted in five guinea pigs. All but one of the KHRI
3-infused animals demonstrated a hearing loss of > 10 dB in the treated ear. In
five of 11 animals the threshold shift was 30 dB or more, and all had hair cell
losses. In one guinea pig infused with 2 mg/ml of antibody, the organ of Corti
was absent in the basal turn of the infused ear. This ear had a 45-50 dB
threshold shift but, curiously, no detectable antibody binding in the residual
organ of Corti. Organ of Corti tissue was fragile in antibody-infused ears.
Breaks within the outer hair cell region occurred in 5/11 infused ears. The
contralateral ears were normal except for one noise-exposed animal that
demonstrated hair cell loss in the uninfused ear. Three animals were exposed to 6
kHz noise (108 dB) for 30 min on day 7. Antibody access to the organ of Corti may
be increased in animals exposed to noise, since the strongest in vivo binding was
observed in noise-exposed animals. Loss of integrity of the organ of Corti seems
to be the primary mechanism of inner ear damage by KHRI-3 antibody. The binding
of KHRI-3 antibody in new scars suggests a role of the antigen in scar formation.
Antibodies with binding properties similar to KHRI-3 have been detected in 51% of
patients diagnosed with autoimmune sensorineural hearing loss; thus, it seems
likely that such autoantibodies also may have pathologic effects resulting in
hearing loss in humans.
PMID- 10190752
TI - The effect of combined administration of cadmium and furosemide on auditory
function in the rat.
AB - A number of heavy metals have been associated with toxic effects to the
peripheral or central auditory system. These include lead, arsenic, mercury,
platinum and organic tin compounds. In addition, the ototoxic effects of some
metals may be potentiated by other factors. However, the auditory effects of
cadmium have not previously been reported. The purpose of the present study was
to investigate the potential ototoxic effects of cadmium from an acute dosage,
and its potentiation by furosemide. Auditory brainstem response (ABR) thresholds
were measured in adult Sprague-Dawley rats. Rats received either cadmium chloride
(5 mg/kg, i.p.) followed by saline (4 ml/kg, i.p.). cadmium chloride followed by
furosemide (200 mg/kg, i.p.), or furosemide alone. Follow-up ABRs were carried
out 7 days post-treatment and threshold changes were compared between each
treatment group. No significant threshold change was seen for the cadmium
chloride plus saline treated or the furosemide treated animals. However,
significant threshold elevations were observed in animals receiving cadmium
chloride plus furosemide. In addition, scanning electron microscopy revealed
extensive hair cell loss in animals treated with cadmium chloride and furosemide.
Although functional auditory changes were not seen after the administration of
cadmium alone, the potentiation of threshold changes by furosemide suggests that
cadmium may be ototoxic under certain conditions.
PMID- 10190753
TI - Auditory midbrain laminar structure appears adapted to f0 extraction: further
evidence and implications of the double critical bandwidth.
AB - The psychoacoustic 'critical bandwidth' (CB), e.g. approximately 2.6 semitones (=
0.22 octave) at 1.5-3 kHz, is known from many spectral integration phenomena. Cat
data suggest that it is represented in the inferior colliculus (IC) (Ehret and
Merzenich, 1985, Science 227, 1245-1247), where it is consistently related to the
fibrodendritic laminae (Schreiner and Langner, 1997, Nature 388, 383-386). The
recent discovery of the CB and the double CB (2CB) in the statistics of frequency
spacing of spontaneous otoacoustic emissions (Braun, 1997. Hear. Res. 114, 197
203) has initiated further investigations of the novel phenomenon of 2CB. Meta
analysis of psychoacoustic valuation studies of pure-tone intervals again
revealed the effects of CB and 2CB. Valuations showed a significant stepwise
change with interval size: 2CB indifferent.
Scrutiny of cat and human data indicated that for both species, at least in the
midspectrum (1-3 kHz in humans), the tonotopic ranges within single IC laminae
and the tonotopic distances between neighboring laminae may equal 1 CB (distances
to second next laminae being 2CB). This unique architecture would provide the
most economical neural convergence of period information from pairs of adjacent
harmonic partials 3-6 of complex sound. The resulting summed postsynaptic
potentials would thus contain a beat frequency equaling f0 of sound input and
being detectable by the known neural behavior of characteristic periodicity
response.
PMID- 10190754
TI - Ultrastructural localization of megalin in the rat cochlear duct.
AB - Megalin is an endocytic receptor predominantly expressed in the kidney proximal
tubule cells. In the present study, localization of megalin was examined using a
post-embedding immunogold method in the rat cochlear duct. Marginal cells of the
stria vascularis were labeled on the apical surface, but not on the basolateral
surface. This localization pattern resembles kidney proximal tubule cells.
Immunoreactivity was also detected on various other cells, including epithelial
cells of the spiral prominence and epithelial cells of Reissner's membrane. In
contrast, virtually no gold particles were seen on intermediate cells and basal
cells of the stria vascularis, mesothelial cells of Reissner's membrane or
fibrocytes in the lateral wall. Also unlabeled were cells in the tympanic wall of
the cochlear duct, including sensory cells and supporting cells of the organ of
Corti. The present findings show the involvement of megalin in endocytosis of
marginal cells and are suggestive of different uptake mechanisms for
aminoglycosides in the kidney proximal tubule cells and in the cochlear sensory
cells.
PMID- 10190755
TI - Forward and backward masking with brief impulsive stimuli.
AB - The forward and backward masking effect of a 20-micros pulse was measured for
delays ranging from 0 to -/+4 ms. Masking is not a monotonic function of delay in
either forward or backward masking. For two of the three observers, the asymmetry
in which forward masking exceeds that of backward masking is small for delays
less than 500 micros. The implications of the data for the contribution of
masking to the precedence effect are considered.
PMID- 10190756
TI - Noise-induced hearing loss in the noise-toughened auditory system.
AB - The auditory system, toughened by an interrupted noise exposure, has been shown
in several reports to be less affected by (or protected from) a subsequent high
level noise exposure. Exposure to 115 dB peak SPL, 1 kHz narrow band (400 Hz)
transients presented l/s, 6 h/day, to four groups of chinchillas produced a 10-28
dB toughening effect across the 0.5-8.0 kHz test frequency range. Following
either a 30 day or an 18 h recovery period the animals were exposed to the same
impulses but presented at 121 or 127 dB peak SPL for five uninterrupted days,
thus producing an asymptotic threshold shift (ATS) condition. Comparisons between
toughened and untoughened control subjects showed: (1) During the 121 dB exposure
there was a statistically significant reduction of 10-25 dB in ATS across the
entire test frequency range. Thirty days following the 121 dB exposure there were
no significant differences in the postexposure permanent effects on thresholds
and sensory cell loss. (2) During the 127 dB exposure only the group with the 30
day interval between the toughening and traumatic exposures showed a small
(approximately 10 dB), statistically significant, frequency-specific (8 kHz),
reduction in ATS. Thirty days following the 127 dB exposure a statistically
significant protective effect on threshold was measured only at 16.0 kHz.
However, both toughened groups showed less inner hair cell loss at and above 1.0
kHz, while only the group with the 18 h interval between the toughening and
traumatic exposures showed less outer hair cell loss at and above 1.0 kHz. There
were no systematic differences in the response of the toughened animals that
could be attributed to the 30 day or 18 h post-toughening interval.
PMID- 10190757
TI - Differentiation of cyst-forming stria vascularis tissues in vitro.
AB - The marginal cells of the stria vascularis possess distinctive morphological
characteristics associated with their role in endolymph production.
Interestingly, when stria-derived epithelial cells are grown in association with
the underlying mesenchyme, the final differentiation of these cell types does not
occur. Beyond the rudimentary polarity that is established, similar to that shown
in epithelial monolayers, cells in culture bear only a slight resemblance to
their marginal cell counterparts in vivo. The ultrastructural features that
typify these epithelia, extensive cytoplasmic invaginations, with an abundance of
mitochondria, and darkly stained cytoplasm, are not evident under standard
culture conditions. In order to determine whether fluid transport, a key function
of the stria vascularis, has an effect on the ultrastructural morphology, we
examined de novo stria vascularis tissues that formed a fluid-filled cyst in
vitro. We found that only cells associated with the luminal structure
demonstrated dark cytoplasmic staining and amplification of the basolateral
membrane of the marginal cells. Additionally, other epithelial features, such as
mitochondria-rich and microvilli-rich cells, were observed in cyst-forming
tissues. The enhancement of the marginal cell specializations was not as robust
as that observed in vivo; however, they were clearly more extensive when compared
to cells in the same culture that were not associated with a fluid-filled lumen.
Thus it appears that fluid transport may be necessary to maximize differentiation
of stria vascularis tissues in vitro.
PMID- 10190758
TI - St. John's wort: a new alternative for depression?
AB - OBJECTIVE: The primary purpose of this article is to review the existing
literature concerning the therapeutic uses, adverse effects, and possible drug
interactions of St. John's wort (Hypericum perforatum) as compared to other
antidepressant medications. METHODS: Reference material was obtained through
database searches with time restrictions of 1985 to the present. Studies selected
were those written in the English language which compared the role of St. John's
wort, tricyclic antidepressants, monoamine oxidase inhibitors, and serotonin
selective reuptake inhibitors in the treatment of depression. Other studies were
selected based on their evaluation of the safety and efficacy of St. John's wort
as an antidepressant for a minimum of four weeks. RESULTS: A review of existing
literature recognized nine clinical trials that reported the efficacy of St.
John's wort as compared to placebo and to other antidepressant medications. Of
these nine, four controlled studies were chosen based upon their large patient
populations and their consistency in brand and dosage of St. John's wort used.
These four studies demonstrated that St. John's wort was as effective as other
antidepressant medications and more effective than placebo, as the clinical
symptoms of depression greatly decreased upon administration of H. perforatum.
The side-effect profile of H. perforatum at this time appears to be superior to
any current U.S.-approved antidepressant medication. CONCLUSIONS: From the
existing literature, St. John's wort appears to be a safe and effective
alternative in the treatment of depression. Tricylic antidepressants and
monoamine oxidase inhibitors can produce serious cardiac side-effects, such as
tachycardia and postural hypotension, and many unwanted anticholinergic side
effects, including dry mouth and constipation. St. John's wort has proven to be
free of any cardiac, as well as anticholinergic, side-effects normally seen with
antidepressant medications. Based upon limited studies, St. John's wort appears
to be an acceptable alternative to traditional antidepressant therapy, although
trials on a larger scale are warranted in this area. Hypericum is available to
the lay public as an over-the-counter preparation and may be misused if not fully
understood.
PMID- 10190759
TI - Bioequivalence evaluation of two sertraline tablet formulations in healthy male
volunteers after a single dose administration.
AB - SUBJECTS, MATERIAL AND METHODS: According to a randomized two-period crossover
design, 12 Chinese male volunteers were treated with 2 sertraline tablet
formulations, one was made in China as test tablet, the other was made in England
as reference tablet. Each volunteer received each sertraline in a single dose of
150 mg. The 2 medications were carried out by a wash-out phase of 23 days. Blood
samples were obtained just before dosing and at 10 time points until 96 hours
after administration, and plasma sertraline concentrations were determined by a
sensitive gas-chromagraphy electron-capture method with a lower limit of
quantification of 0.625 ng/ml. The bioequivalence of 2 formulations was evaluated
by the shortest 90% confidence interval method which corresponds to the two one
sided test method. RESULTS: The point estimate (90% confidence interval) of the
mean ratio (test/reference) for AUC(0-96) was 97.19% (82.66% to 122.33%), for
Cmax 96.27% (83.64% to 121.36%), and for t(l/2) 96.31% (85.43% to 119.57%).
Regarding Tmax (test-reference), the 90% confidence interval ranged from -4 to +4
hours, but the difference between the Tmax values of 2 products is clinically of
minor importance. CONCLUSION: Therefore, it can be concluded that 2 sertraline
tablet formulations are bioequivalent. administration, sertraline is slowly
absorbed with peak plasma concentrations at 6 - 8 h, and has a terminal
elimination half-life of approximately 26 h, indicating once-daily dosing is
available. Clinically, it can be taken either in the morning or in the evening,
with or without food [Ronfeld et al. 1997b]. In addition, it also exhibits higher
plasma protein binding up to 97% and extensive first-pass metabolism. By
demethylation, sertraline is metabolized primarily to N-demethylsertraline, and
then eliminated by hydroxylation arid conjugation [Tremaine et al. 1989]. This
study aimed at assessing of bioequivalence of two sertraline formulations
(produced in China and England, respectively) in healthy male volunteers after a
single dose administration.
PMID- 10190760
TI - Oxidative stress resulting from hemolysis and formation of catalytically active
hemoglobin: protective strategies.
AB - OBJECTIVES: The possible oxidative complications induced by free hemoglobin (Hb)
released during the blood storage are discussed together with therapeutic
strategies using vitamin E and specific inhibitor haptoglobin. Prooxidative
properties of Hb in blood have been examined using LDL as a marker for oxidative
stress, which contribute to toxicity observed in a number of pathologies
aggravated by hemolysis or hemorrhagic lesions as well as after the transfusion
of stored blood. MATERIALS: Experiments were performed using fresh blood or
stored blood that was obtained from a blood bank on the day corresponding to the
identified expiration date. METHODS: Oxidation of LDL was determined by means of
the formation of mildly oxidized LDL (LDL-) using anion exchange chromatography.
Concentrations of Hb were determined spectrophotometrically. RESULTS: Hb-mediated
oxidative processes in cellular membranes have been well documented over the past
decade. We showed that catalytic activity of Hb released during blood storage was
sufficient to increase the proportion of LDL- fraction in blood after 4 h
incubation at 37 degrees C. The intensity of this oxidative process as well as
the release of Hb varied in different donors and may depend on the antioxidant
capacity of blood. Accumulation of Hb during storage was significantly decreased
in range of 15 - 32% in blood supplemented with low concentrations of alpha-,
gamma-tocopherols. Similar effects were observed in the presence of low
concentrations of haptoglobin, which has been reported as a specific inhibitor of
hemoglobin-mediated oxidation. CONCLUSIONS: The specific inhibition of hemoglobin
mediated oxidation in lipoproteins and cellular membranes may improve the quality
of stored blood and help to decrease complications arising from oxidative stress
after transfusions or during hemolytic events. Based on growing evidence for a
role of oxidatively modified LDL in atherosclerosis, hemolytic pathologies should
receive further consideration as risk factors for cardiovascular disease.
PMID- 10190761
TI - Safety and tolerability of naproxen ophthalmic solution in comparison to placebo.
AB - BACKGROUND: Naproxen is a classic non-steroidal anti-inflammatory drug (NSAID)
with established analgesic and anti-inflammatory potency. Its action is related
to cyclooxygenase inhibition and consequent decrease in prostaglandin
concentration in various fluids and tissues. Since prostaglandin release is
involved in several ocular alterations, various NSAID eye drops have come into
use in the clinical setting during the last decade. SUBJECTS, MATERIAL AND
METHODS: A randomized, double-blind, placebo-controlled, three-way crossover
design phase I was performed in 12 healthy volunteers to determine both tolerance
and safety of a new NSAID ophthalmic solution containing sodium naproxen (0.1%
and 0.2%). Both single dose and repeated dose (TID for 6 days) instillation were
performed. Evaluation was entirely based upon tolerance criteria. Subjective and
objective signs of ocular irritation and subject comfort preference were
evaluated. Also medical examination, hematology, blood chemistry and urine
analysis were also assessed to evaluate any possible effect of the test drugs and
control. RESULTS: Neither ophthalmic tolerance parameters nor vital signs or
laboratory parameters were influenced by treatments. A slight hyperemia of the
conjunctiva was the only change observed in the eye during the study, whereas the
only symptom mentioned was burning. CONCLUSION: It is concluded that both
tolerability and safety of 0.1% and 0.2% naproxen solution are acceptable after
single and repeated conjunctival administration.
PMID- 10190762
TI - Effects of benidipine hydrochloride on 24-hour blood pressure and blood pressure
response to mental stress in elderly patients with essential hypertension.
AB - OBJECTIVE: The effects of a new dihydropyridine calcium antagonist, benidipine
hydrochloride, on 24-hour blood pressure and blood pressure response to mental
arithmetic test were investigated. SUBJECTS: Ten elderly patients with essential
hypertension (mean age: 65+/-4 years; 7 male and 3 female). METHOD: After a
control period of 4 weeks, 4 mg benidipine was administered once daily in the
morning for 12 weeks. Ambulatory blood pressure was monitored using a non
invasive automatic portable device with the cuff-oscillometric method at the end
of both the control and treatment periods. RESULTS: Benidipine administration
significantly decreased 24-hour blood pressure, while little change was noted in
heart rate. Daytime blood pressure decreased significantly, from 148.2+/
11.5/90.8+/-8.8 to 133.8+/-9.2/82.5+/-10.8 mmHg. However, no significant decrease
in nighttime diastolic blood pressure was noted, and the decrease in nighttime
systolic blood pressure was small (from 129.8+/-9.9/77.1+/-7.6 to 121.8+/
10.1/74.7+/-9.1 mmHg). No significant changes were observed in diurnal
variability of blood pressure and heart rate. The decrease in systolic blood
pressure by benidipine administration showed a significant positive correlation
with systolic blood pressure before treatment in the 24-hour and daytime periods.
Single cosinor analysis showed that benidipine administration significantly
decreased MESOR of both systolic and diastolic blood pressure, without an
increase in amplitude. Both systolic and diastolic blood pressure during mental
arithmetic test were significantly decreased after treatment with benidipine, and
the increase in systolic blood pressure induced by mental arithmetic test was
also significantly attenuated. CONCLUSIONS: These findings indicate that
administration of benidipine once daily in the morning effectively decreases
blood pressure and attenuates blood pressure response to mental stress. Neither
reflex tachycardia, deterioration of diurnal blood pressure change, nor excessive
lowering of nighttime blood pressure was observed after benidipine
administration. It is suggested that benidipine is a potent and long-lasting
calcium antagonist which may be useful for the treatment of elderly hypertensive
patients with cardiovascular disease.
PMID- 10190763
TI - Bioequivalence of allopurinol-containing tablet preparations.
AB - AIM: The study was undertaken to prove the bioequivalence of two allopurinol
tablet preparations. SUBJECTS, MATERIALS AND METHODS: The relative
bioavailability of allopurinol from two tablet preparations (Uribenz vs. Zyloric
300) was estimated on 18 volunteers of both sexes in an open randomized study by
administering one tablet of each preparation at an interval of 2 weeks. The
plasma concentrations of allopurinol and its active metabolite oxypurinol were
measured over a time-period of 72h by HPLC. RESULTS: While the mean AUC(0-72)
values of allopurinol and oxypurinol after the test and reference preparations
are entirely identical (5.33 vs. 5.21 and 137.95 vs. 137.96 microg h ml(-1),
respectively), the C(max) values of oxypurinol unlike those of allopurinol show
small differences (4.59 vs. 4.78 and 1.91 vs. 193 microg/ml, respectively).
According to the parametric and non-parametric analysis, the quotients
AUC(T)/AUC(R) and C(maxT)/C(maxR) lie within the confidence intervals 0.8 to 1.2
and 0.7 to 1.3 respectively With regard to the t(max) of allopurinol, the
differences of test and reference preparations are between 0.10 to 0.05h and of
oxypurinol between -0.10 to 0.87h (parametric analysis). Both, Uribenz 300 and
Zyloric 300 caused a maximum decrease of the uric acid concentration in the
volunteers by 18% after 10 and 24h, respectively. CONCLUSION: Thus the
bioequivalence of the allopurinol tablet preparations is demonstrated.
PMID- 10190764
TI - Bioequivalence study of two morphine extended release formulations after multiple
dosing in healthy volunteers.
AB - AIM: Two extended release (ER) formulations of morphine sulphate (30 mg each),
Oramorph SR (test) and a marketed reference formulation (MST Mundipharma
Retardtabletten), were investigated for their relative bioavailability at steady
state: METHODS: The study was designed as a single-centre, open-label, two-period
crossover, pharmacokinetic comparison in 28 healthy male volunteers and was
completed in 23 subjects. The determination of morphine and its metabolite
morphine-6-glucuronide in plasma was done by HPLC with electrochemical detection
after solid-phase extraction. RESULTS: Under steady-state conditions in the first
dosing interval, mean maximum plasma concentrations for morphine were 19.1 ng/ml
(CV% 41) for Oramorph SR 30 mg and 19.1 ng/ml (CV% 33) for MST-30 Mundipharma
Retardtabletten. Geometric mean AUC(0-12) values were calculated as 108 ngxh/ml
(CV% 40) for Oramorph SR 30 mg and as 118 ng x h/ml (CV% 30) for the reference
formulation. The plasma concentrations of the major metabolite, morphine-6
glucuronide, were found to be generally in a higher range compared to the parent
compound. The 90% confidence intervals of test to reference ratios calculated for
all relevant parameters (AUC, C(max), PTF) for both the parent compound and
morphine-6-glucuronide were all within the limits of 80 - 125%. The most frequent
adverse events (AE > 10%) during Oramorph SR 30 mg treatment were headache (36%),
dizziness (18%), nausea (21%), vomiting (21%) and pruritus (11%). During
treatment with MST-30 Mundipharma Retardtabletten, the most frequent AEs were
headache (29%), dizziness (13%), nausea (29%) and vomiting (29%). CONCLUSION: The
results demonstrate bioequivalence of Oramorph SR 30 mg and MST-30 Mundipharma
Retardtabletten.
PMID- 10190765
TI - Respiratory ammonia output and blood ammonia concentration during incremental
exercise.
AB - The aim of this study was to investigate whether the increase of ammonia
concentration and lactate concentration in blood was accompanied by an increased
expiration of ammonia during graded exercise. Eleven healthy subjects performed
an incremental cycle ergometer test. Blood ammonia, blood lactate and the amount
of expired ammonia were measured until 30 minutes post exercise. The expired air
was guided through a flow chamber filled with a sulphuric acid solution to trap
the expired ammonia. Blood ammonia, blood lactate increased more than
proportionally and the amount of expired ammonia (in micromol/min) increased
exponentially with the workload. Post-exercise the amount of expired ammonia
decreased within a few minutes back to pre-exercise levels while the
concentrations of lactate and ammonia in blood decreased much more slowly and
were still elevated after 30 minutes of recovery. We conclude that the more than
proportional increase of ammonia and lactate during graded exercise, is
accompanied with an exponential increase of expired ammonia output. Faster and
more accurate ammonia gas detection techniques are necessary to quantify more
precisely the respiratory ammonia output during graded exercise.
PMID- 10190766
TI - Effects of iron supplementation on total body hemoglobin during endurance
training at moderate altitude.
AB - The aim of the study was to test the hypothesis that iron supplementation in well
trained non-iron-depleted athletes leads to an enhanced increase of total body
hemoglobin (TBH) during training at moderate altitude. Therefore, the members of
the national German boxing team were randomly assigned to treatment with ferrous
glycine-sulfate (1335 mg equivalent to 200mg elementary iron daily) or with
placebo during 18 days of endurance training at moderate altitude (1800 m).
Before and after altitude training TBH was determined by CO-rebreathing, measures
of exercise performance were determined with an incremental treadmill test.
Before, during and after the stay at moderate altitude erythropoietin (Epo),
reticulocytes (Retics) and parameters of iron metabolism were measured in venous
blood. The results show that TBH did not change significantly in the placebo
group and even slightly, but significantly decreased in the iron-treated group.
However, there was a significant increase of Epo and Retics in both groups during
training at moderate altitude whereas parameters of iron metabolism remained
unchanged. VO2max did not change either. To test whether a training-induced
hemolysis, an increased urinary iron excretion or gastrointestinal blood loss
could explain the unexpected drop of TBH we tested most of the boxers again
during a similar training camp at low altitude (400-1000 m) to obtain measures of
hemolysis, urinary iron excretion and occult hemoglobin loss with the stools.
Although there were signs of an increased erythrocyte turnover no iron loss could
be observed. We conclude that 18 days of endurance training at an altitude of
1800 m does not lead to an increase of TBH in non-iron-depleted athletes with and
without iron supplementation.
PMID- 10190767
TI - Postural control of ballet dancers: a specific use of visual input for artistic
purposes.
AB - Dance is a specific expression of human motor behaviour. This artistic physical
activity depends upon an effective technical training with important postural
components and necessitates the codification of sensory inputs to build mental
representations of the action to be produced. Proprioception and vision being two
fundamental sensory modalities in classical ballet, this study attempted to
determine the importance of the visual input for postural control during the
practice of this activity. First, this work compared the performances of 18
professional ballet dancers and 46 non-dancers on a platform of forces during
static posturographic tests in open or closed eyes situation. Then, we studied
how professional dancers achieve balance in postures specific of classical
ballet: on demi-pointe and on pointe. The results indicate that visual inputs are
important in classical ballet since dancers only performed better than controls
in eyes open conditions. The similar results obtained on pointe with eyes open or
closed conversely suggest that training in classical ballet develops specific
modalities of balance which are not transferable to posture control in daily life
situations.
PMID- 10190768
TI - Effects of moderate dietary manipulations on swim performance and on blood
lactate-swimming velocity curves.
AB - Blood lactate responses are commonly employed for evaluation and prescription of
training programmes. The purpose of the present studies was to examine the
effects of dietary manipulations on both swim performance and on the relationship
between blood lactate and swimming velocity. The first study engaged 8 subjects
in a regimen to reduce muscle glycogen by a combination of diet and training.
Subjects were monitored under a normal mixed diet comprising 53.6+/-7.8%
carbohydrate (CHO) and under a decreased CHO condition (39.4+/-10.7% CHO) over 3
days. Mean swim performance decreased significantly (P<0.05) over 400 yards as a
result of the carbohydrate reduction regimen. Mean blood lactates were reduced as
a consequence of the glycogen depletion regimen following swims at 85% and 100%
of maximum velocities. The swimming velocity corresponding to 4 mM blood lactate
(V-4 mM) was altered from 0.67+/-0.04 m x s(-1) on a mixed diet to 0.70+/-0.05 m
x s(-1) on a CHO-reduced diet. The second study employed 7 subjects in a regimen
to enhance muscle glycogen stores. Subjects were monitored over 3 days under a
normal diet (52.7+/-4.4% CHO) and on a separate occasion under an increased CHO
intake (59.2+/-3.7% CHO). In contrast to the first study, mean swim performance
improved over 100 yards and 400 yards (P<0.05). Mean blood lactates were
evaluated after the carbohydrate-rich regimen at both 85% and 100% swim
velocities (P<0.05). The mean swim velocity associated with V-4mM was
paradoxically reduced from 0.69+/-0.05 to 0.67+/-0.04 m x s(-1) as a result of
the increased CHO condition. The results indicate that a moderate reduction in
CHO intake alters swimming performance adversely whereas a moderate elevation in
CHO intake above the normal diet improves performance. The dietary manipulations
affected the response of blood lactate to both submaximal and maximal swimming
velocities. The observations highlight the limitations of applying lactate
response curves to swim training.
PMID- 10190769
TI - Anti-inflammatory doses of ibuprofen: effect on neutrophils and exercise-induced
muscle injury.
AB - The purpose of the study was to determine the effect of anti-inflammatory doses
of ibuprofen on neutrophils, neutrophil O2* production, and markers of muscle
injury. Males (n=10) performed 2 bouts of one-arm eccentric exercise on opposite
arms separated by three weeks. Subjects received 2400 mg x d(-1) of ibuprofen or
a placebo 5 d before exercise and during 10 d of recovery. Measurements were made
before the treatments, pre-exercise, at 4 h, and at 1, 2, 3, 4 and 10 d post
exercise. Circulating neutrophil counts were similar between the treatments at
the sampling points. Neutrophil counts were higher (p<0.05) for ibuprofen and
were elevated (p<0.05) at 4h post-exercise relative to pre-exercise in both
treatments. Stimulated neutrophil O2* production was lower for ibuprofen relative
to placebo at pre-exercise and was increased (p<0.05) at 4 h and 4 d of both
treatments. CK activity at 3 d post-exercise was lower (p<0.05) for ibuprofen
relative to placebo. Isometric strength, soreness, tenderness, and arm angles
were similar between the treatments. In conclusion, anti-inflammatory doses of
ibuprofen reduced CK activity but not the neutrophil response or other indirect
markers of muscle injury during recovery from eccentric arm exercise.
PMID- 10190770
TI - Exercise-induced signs of muscle overuse in children.
AB - Signs of overuse after intense muscular exertion are well described in adults,
while little research has been conducted in children. The aim of the study was to
investigate some indirect markers of muscle damage in 13 years old boys following
two different protocols of one-leg stepping exercise to exhaustion. This stepping
exercise was performed by two experimental groups with different contributions of
concentric and eccentric contractions in a 1:1 vs 1:2 ratio of timing. Subjective
soreness perception and maximum voluntary isometric force of the knee extensor
muscles were measured immediately prior to and immediately following the
exercise, and at 1, 3, 24, 48, 72, 96 hours post exercise. Metabolic markers of
exercise stress were taken at similar time intervals and included plasma
glutathione concentrations as a marker for oxidative stress, circulating
leukocyte numbers, and plasma creatine kinase (CK) activity. All parameters
studied demonstrated a higher level of muscular exertion, with more evident signs
of overuse in the group with the more eccentric contribution. Complete recovery
was achieved between 72 and 96 hours after exertion. However, in this group of
boys, the CK activity did not show the typical adult-like increase. Therefore the
wide use of CK as an indicator of intense muscle exertion was not supported in
this group of children. It can be concluded that children, like adults,
experience similar degrees of muscle disturbances following intense exercise and
that they may recover more quickly from such exercise.
PMID- 10190771
TI - Saliva cortisol, testosterone and T/C ratio variations during a wrestling
competition and during the post-competitive recovery period.
AB - This study presents saliva cortisol (C) and testosterone (T) levels in a group of
15 young wrestlers (national and international) during a two-days competition.
Values are compared to references established on a resting day (3 weeks before
the competition). Post-competition recovery was studied by recording evening
hormonal levels (5.30 pm) for 8 days. RESULTS: C levels increased sharply (about
2.5 fold resting levels) throughout the competition with no further changes in T
levels. The rise in C appeared before entering the competition, traducing a
striking phenomenon of anticipation. At the end of the competition, C levels fell
very quickly (within 1.5 h) to basal value when T rose significantly, resulting
in a very high T/C ratio. During the recovery period, C levels corresponded to
basal ones and T remained high, resulting in a high T/C ratio (>30% than basal
one) till the 5th day. CONCLUSION: Competition resulted in a low T/C ratio,
considered as a catabolic phase. The recovery which is associated with a feeling
of tiredness and an incapacity to train strenuously recognized by the trainers,
paradoxically corresponded to a high T/C ratio (so-called anabolic phase).
PMID- 10190772
TI - The ventilatory threshold, heart rate, and endurance performance: relationships
in elite cyclists.
AB - The purpose of this study was to investigate the validity of the ventilatory
response during incremental exercise as indication of endurance performance
during prolonged high-intensity exercise under field test conditions in elite
cyclists. The ventilatory threshold (VT) was assessed in 14 male elite cyclists
(age 22.4+/-3.4 years, height 181+/-6 cm, weight 69.2+/-6.8 kg, VO2max 69+/-7 ml
x min(-1) x kg(-1)) during an incremental exercise test (20 W x min(-1)). Heart
rate and oxygen uptake were assessed at the following ventilatory parameters: 1.
Steeper increase of VCO2 as compared to VO2 (V-slope-method); 2. Respiratory
exchange ratio (RQ)=0.95 and 1.00; 3. VE/VO2 increase without a concomitant
VE/VCO2 (VE/VO2 method). Three weeks following the laboratory tests, the ability
to maintain high-intensity exercise was determined during a 40 km time trial on a
bicycle. During this time trial the mean heart rate (HR(TT)) and the road racing
time (TT) were assessed. The V-slope-method and the VE/VO2 method showed
significant correlations with TT (V-slope: r = -0.82; p<0.001; 90% interval of
confidence = +/-82 sec; VE/VO2: r=-0.81; p<0.01; 90% interval of confidence = +/
81 sec). Heart rate at the ventilatory parameters and at the maximum heart rate
(HRmax) showed significant correlations with HR(TT). The V-slope-method is the
preferred method to predict heart rate during prolonged high-intensity exercise
(r=0.93; p<0.0001; 90% interval of confidence: +/-4.8 beats x min(-1)). For
predicting heart rate during prolonged high-intensity exercise using an
incremental exercise test (20 W x min(-1)), without the knowledge of ventilatory
parameters, we recommend using the regression formula: H(TT)=0.84 x Hmax + 14.3
beats x min(-1) (r=0.85; p<0.001).
PMID- 10190773
TI - Lactate and cardiopulmonary responses to simulated arm-pulling and leg-kicking in
collegiate and recreational swimmers.
AB - Investigations into the changes due to training in the metabolism of the arms or
the legs in swimmers of different training status are limited. The purpose of
this study was to compare the lactate and cardiopulmonary responses to simulated
arm-pulling and leg-kicking in collegiate and recreational swimmers. Sixteen
males (9 collegiate swimmers; SW, 7 recreational swimmers; RSW, mean+/-SD; age
22+/-3 years, body mass 81+/-9 kg, stature 1.84+/-0.06 m), gave written consent
and performed continuous incremental exercise tests using either simulated front
crawl arm-pulling or leg-kicking. Lactate concentration (HLa) and oxygen
consumption (VO2) were determined at 20 W intervals and at exhaustion (HLa(peak);
VO2(peak)). The exercise intensity at a lactate concentration of 4 mM (EI4mM) and
at exhaustion (EI(peak)) for arm-pulling and leg-kicking were also established.
The arm:leg ratios for EI4mM, HLa(peak) and VO2(peak) were computed. The results
showed that for arm-pulling, the SW had higher EI4mM (P=0.02), EI(peak)
(P=0.006), but lower HLa(peak) (P=0.03) compared to the RSW. For leg-kicking,
none of the responses differed significantly. These results suggest that it is
rather the metabolism and local muscle endurance of the arms that are enhanced
with competitive swimming endurance.
PMID- 10190774
TI - Ventilatory, lactate-derived and catecholamine thresholds during incremental
treadmill running: relationship and reproducibility.
AB - Anaerobic threshold as a basic criterion of training recommendation can be
estimated by various parameters. The purpose of this study was to investigate the
relationship and the reproducibility of ventilatory, lactate-derived and
catecholamine thresholds of an incremental treadmill exercise. Therefore, 11 male
subjects underwent two incremental treadmill tests within 7 days. The lactate
threshold (LT) was determined at the lowest value of the lactate-equivalent
(ratio lactate/performance). The individual anaerobic threshold (IAT) was
calculated at LT+1.5 mmol/L lactate. The ventilatory thresholds, using mass
spectrometry, were defined by the V-slope method (AT) and at the deflection point
of end-tidal CO2 (ET-CO2) concentration (RCP). The thresholds of epinephrine (TE)
and norepinephrine (TNE) were calculated in the manner of LT. The running
velocities were highly reproducible at LT (test-retest correlation coefficient
r=0.90), IAT (r=0.97), AT (r=0.88) and RCP (r=0.95). By contrast TE (r=0.49) and
TNE (r=0.46) showed a poor reproducibility. TE and TNE occurred 5-11% below LT
and AT with a low correlation to LT and AT. LT was found 4% below AT, both were
correlated with r=0.70 (p<0.01, test 1) and r=0.95 (p<0.01, test 2). IAT occurred
7-8% above RCP, in both tests a close correlation was found between IAT and RCP
of r=0.97 (p<0.01). In summary, the ventilatory and lactate-derived thresholds
show a high and similar reproducibility, but the catecholamine threshold does
not. In the present exercise protocol, there are systematic differences between
the lactate-derived and ventilatory thresholds, in spite of a close relationship,
and these must be taken into account in recommendations derived for training.
PMID- 10190775
TI - Effects of exercise intensity, duration and recovery on in vitro neutrophil
function in male athletes.
AB - The aim of the present study was to compare the effects of exercise at 80% VO2max
(resulting in fatigue within 1 h) with more prolonged exercise at a lower work
rate (55% VO2max for up to 3 h) on blood neutrophil function and plasma
concentrations of cortisol, glutamine and glucose. Eighteen healthy male subjects
(mean+/-SD age 22.5+/-3.7 yrs, VO2max 60.1+/-6.6 ml x kg(-1) x min(-1)) cycled on
an electrically braked ergometer at 80% VO2max to fatigue (37+/-19 min). On
another occasion, separated by at least one week, subjects performed exercise on
the same ergometer at 55% VO2max for 3 h or to fatigue, whichever was the sooner.
Mean exercise time was 164+/-23 min. The order of the trials was randomised. Both
exercise bouts caused significant (p<0.05) elevations of the blood leucocyte
count and plasma cortisol concentration and reductions in the in vitro neutrophil
degranulation response to bacterial lipopolysaccharide and oxidative burst
activity. After exercise at the lower work rate for a longer duration, plasma
cortisol concentration was higher, blood leucocyte and neutrophil counts were
higher, blood lymphocytes, plasma glucose and indices of neutrophil function were
lower than those observed at 80% VO2max. Plasma glutamine only fell significantly
during recovery after the more prolonged exercise. We conclude that when exercise
is very prolonged, the diminution of innate immune function is greater, or at
least as great as that observed after fatiguing exercise at higher work rates.
Furthermore, reductions in neutrophil function after exercise at 80% VO2max were
not related to changes in the plasma glutamine concentration, although both
plasma glutamine and neutrophil function were decreased at 1 and 2.5 h post
exercise in the long duration exercise trial.
PMID- 10190776
TI - Relation between aerobic fitness level and stress induced alterations in
neuroendocrine and immune function.
AB - Alterations in neuroendocrine and immune function were examined in sedentary
(n=15) (VO2peak; 31.4+/-0.7 ml x kg(-1) x min(-1); 24.4+/-1.2yr), moderately
active (n=15) (VO2peak; 45.4+/-1.1 ml x kg(-1) x min(-1); 24.2+/-1.1 yr) and
aerobically trained (n=15) (VO2peak; 58.8+/-0.9 ml x kg(-1) x min(-1); 24.3+/-1.0
yr) men following exposure to an acute mild psychological stressor. Subjects had
2 min to prepare, and 3 min to deliver a speech in front of 3 observers. Blood
samples were drawn from an indwelling catheter before, during and 30 min
following the speech task (ST). Self-reported measures of anxiety were obtained
prior to and immediately following the stressor. The ST resulted in significant
alterations in the number and function of immune cells, and in self-reported
anxiety scores. Plasma levels of norepinephrine increased during the speech task.
The neuroendocrine and immune response to the chosen stressor were independent of
subject aerobic fitness level.
PMID- 10190777
TI - Moderate and high intensity exercise training in HIV-1 seropositive individuals:
a randomized trial.
AB - HIV-infected individuals are frequently active, but guidelines for exercise in
this population lack scientific support, since studies on the effects of exercise
training on immunologic variables of HIV-1 positive individuals have shown
conflicting results. Exercise capacity, immunologic markers (CD4, CD8 and CD4:CD8
ratio), anthropometric measurements, and depression scores were evaluated to
compare the effects of two intensities of aerobic exercise on HIV-1 seropositive
individuals. Twenty-one healthy subjects (14 men, 7 women), carriers of the HIV-1
virus (CD4>200 cells x mm(-3)), and inactive for at least 6 months, completed a
12 week exercise training program (36 sessions of 1 h, 3 times per week), in a
moderate intensity group (60+/-4% of maximal heart rate) or a high intensity
group (84+/-4% of maximal heart rate). Exercise capacity estimated by treadmill
time was increased significantly in both moderate intensity (680+/-81 s before;
750+/-151 s after) and high intensity (651+/-122 s before; 841+/-158 s after)
groups, but the high intensity group presented a significantly larger increment
(p<0.01). There were no significant changes in the immunologic variables,
anthropometric measurements or depression scores. Thus, HIV-seropositive
individuals that participate in moderate and high intensity exercise programs are
able to increase their functional capacity without any detectable changes in
immunologic variables, anthropometric measurements or depression scores.
PMID- 10190778
TI - The current state of adjuvant therapy for breast cancer: focus on paclitaxel.
AB - Combination chemotherapy may necessitate reduction from optimal doses for many of
the component agents to minimize the risk of additive toxicity. Several
strategies have been investigated to overcome the diminished cell kill resulting
from less than optimal dosing. Key among these are dose-dense therapy (using the
shortest possible intertreatment interval of the reduced doses to increase the
dose intensity and take advantage of tumor cell kinetics) and use of new and
novel anticancer agents. Paclitaxel (Taxol; Bristol-Myers Squibb Company,
Princeton, NJ), the first of the taxane drugs, has come to have a quite
significant role in the new strategies because of its unique mechanism of action
and lack of cross-resistance with other active agents. These two strategies have
been examined alone and in combination in the adjuvant therapy of breast cancer
and the results of many of these studies are presented here. Overall, progress is
being made with dose-dense regimens and with paclitaxel-containing combinations,
and each may play a role in the future of breast cancer management.
PMID- 10190779
TI - Metastatic breast cancer: the role of chemotherapy.
AB - Treatment of metastatic breast cancer remains in flux. A flurry of new
chemotherapeutic agents with activity against this disease has been identified in
recent years, yet breast cancer remains a cause of significant morbidity and
mortality. The taxanes in particular appear to hold promise for improved outcome
and, in fact, are the treatment of choice for salvage therapy. Using the taxanes
in high-dose regimens, with stem cell transplantation, in alternative schedules,
and in combination regimens, including with biologic treatments, is the focus of
future potential advances. Continued investigative energy and the discovery of
novel drugs and therapeutic approaches for addition to established techniques
hopefully will improve outcomes in the next generation of treatment strategies
for metastatic breast cancer.
PMID- 10190780
TI - Kinetic concepts in the systemic drug therapy of breast cancer.
AB - Optimal management of cancer today requires a thorough and up-to-date
understanding of cancer cell kinetics and biochemistry. This report reviews the
history and current standards in these fields and how they affect the
contemporary approach to breast cancer management. Also outlined are recommended
avenues for future research in cytotoxic chemotherapy programs using the
principles of cancer cell kinetics as well as the role of newer approaches,
including biologic agents such as trastuzumab (Herceptin) and antiangiogenesis
agents, in the future therapy of this disease.
PMID- 10190781
TI - Paclitaxel plus nonanthracycline combinations in metastatic breast cancer.
AB - The results of several phase II and some phase III studies are now available in
which the combination of paclitaxel (Taxol; Bristol-Myers Squibb Company,
Princeton, NJ) and nonanthracycline agents are evaluated. The studies demonstrate
the activity and feasibility of these combinations, which achieved response rates
of 40% to 80% and median time to progression that exceeded 6 months. The
potential role of these combinations compared with older non-paclitaxel
containing regimens, in improving quality of life, response rate, and survival in
patients with metastatic breast cancer, however, await the results of
prospective, randomized phase III trials. The next logical step, depending on the
results of planned comparative trials, is to incorporate these combinations in
the neoadjuvant and adjuvant settings.
PMID- 10190782
TI - Concurrent paclitaxel, carboplatin, and radiation therapy for locally advanced
non-small cell lung cancer.
AB - Combination chemotherapy plus radiation therapy for non-small cell lung cancer
has several theoretical advantages: the potential of chemotherapy to
radiosensitize tumors, the possibility of improved local control due to combined
treatment, and the opportunity for spatial cooperation, attacking disease both
locally and systemically and thus potentially increasing response and,
ultimately, survival. The combination of radiotherapy plus standard chemotherapy
(etoposide plus cisplatin) has yielded limited success; therefore, new and novel
chemotherapies have been sought. Paclitaxel (Taxol; Bristol-Myers Squibb Company,
Princeton, NJ), the prototype of a novel class of drugs, the taxanes, has proven
feasible both alone and with other agents in combined-modality regimens with
radiation. Concurrent paclitaxel/carboplatin/radiotherapy appears to offer a
relatively safe and more active regimen to control local and metastatic non-small
cell lung cancer than the current standard. This report reviews the range of
experience with paclitaxel-based combined-modality therapy.
PMID- 10190783
TI - Incorporation of paclitaxel and carboplatin in combined-modality therapy for
locally advanced non-small cell lung cancer.
AB - Combined chemotherapy and thoracic radiation therapy has emerged as a primary
treatment option for locally advanced, unresectable non-small cell lung cancer
(NSCLC). Randomized trials and subsequent metaanalyses have shown a clear
survival benefit with platinum-based combination chemotherapy administered
sequentially or concurrently with hyperfractionated thoracic radiation over
radiation alone. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ)
and carboplatin recently have been evaluated in numerous phase 1/11 trials at
various doses in both sequential and concurrent schedules with thoracic radiation
in patients with locally advanced and unresectable NSCLC. The patterns of failure
in patients treated with concurrent paclitaxel/carboplatin and thoracic radiation
suggest the need for additional chemotherapy either at the front end or after
completion of the concurrent regimen. A large multicenter randomized study
(Locally Advanced Multimodality Protocol) has been initiated to address these
issues of improvement in distant control and to further refine the combined
modality approach for patients with locally advanced NSCLC. Several other
combined-modality regimens incorporating a platinum compound and a novel agent
like gemcitabine, vinorelbine, paclitaxel, or docetaxel have been recently
completed or are in progress. The hope for the immediate future is to define an
"effective" and "optimal" regimen that can be given simultaneously with thoracic
radiation and can result in improved local and systemic control in patients with
regionally advanced NSCLC. Numerous phase II and III trials are currently planned
or under way to further define the efficacy of this novel combination of
paclitaxel/carboplatin in combined-modality programs in an attempt to determine
the optimal administration sequence of chemotherapy and thoracic radiation. These
combined-modality programs are now being integrated into trials for early stage,
potentially resectable disease. Thus, NSCLC is in fact a systemic disease
requiring a multidisciplinary approach for optimal management.
PMID- 10190784
TI - Review of paclitaxel/carboplatin in advanced non-small cell lung cancer.
AB - The management of non-small cell lung cancer (NSCLC) has advanced in the last two
decades. The greatest benefit has been achieved with the development of newer
chemotherapeutic agents with single-agent response rates > or =20%. Recent
research has focused on adding these newer agents to established drugs for NSCLC,
like cisplatin and carboplatin, yielding notable improvement in response and
survival rates. In particular, experience with the combination of carboplatin
plus paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has proved
encouraging. This regimen is effective, tolerable, and easy to administer and has
produced response rates in NSCLC as high as 62%. Phase III trials are under way
to establish the specific role of this regimen in NSCLC. The success of this
combination also is being expanded through studies investigating its combination
in triplets with newer agents, with follow-up therapy via sequential regimens,
and by the addition of biologically based treatments. The results of these trials
will determine the preferred treatment approach to NSCLC for the next decade.
PMID- 10190785
TI - The current role and future prospects of paclitaxel in the treatment of small
cell lung cancer.
AB - When combination regimens containing a platinum compound and etoposide are used,
median survivals in patients with extensive- and limited-stage small cell lung
cancer are 7 to 10 months and 15 to 20 months, respectively. A recent randomized
trial demonstrated equivalent efficacy and decreased toxicity with
carboplatin/etoposide compared with cisplatin/etoposide. Because of excellent
single-agent activity, paclitaxel (Taxol; Bristol-Myers Squibb Company,
Princeton, NJ) has been recently added to various platinum/etoposide
combinations. Phase I/II studies with paclitaxel/cisplatin/etoposide and
paclitaxel/carboplatin/etoposide have demonstrated excellent activity with
acceptable toxicity. Ongoing phase III trials will better define the contribution
of paclitaxel to standard platinum/etoposide regimens. In addition, phase II
trials of novel paclitaxel combinations (e.g., paclitaxel/topotecan,
paclitaxel/carboplatin/topotecan) are ongoing.
PMID- 10190786
TI - Paclitaxel/carboplatin for the initial treatment of advanced ovarian cancer.
AB - In 1996, the combination of cisplatin 75 mg/m2 plus 24-hour infusion of 135 mg/m2
paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) was proved to
prolong survival in comparison with cyclophosphamide/cisplatin in women with
advanced ovarian cancer. As a result, the paclitaxel/cisplatin combination was
recommended to serve as the new standard of care. One year later, a European
Canadian group confirmed the efficacy of paclitaxel/cisplatin in a study in which
the infusion period of paclitaxel was reduced from 24 to 3 hours and the dose of
paclitaxel escalated to 175 mg/m2. These changes resulted in a lower incidence of
myelosuppression but a higher rate of neurotoxicity. Replacing cisplatin with
carboplatin, a platinum analogue without the neurotoxic effects, proved feasible,
and several trials were initiated to compare the safety and efficacy of
paclitaxel/carboplatin with paclitaxel/cisplatin. The results of two of these
studies that have completed accrual and reported preliminary data have shown that
paclitaxel/carboplatin can be administered safely to outpatients, is better
tolerated than paclitaxel/cisplatin, and results in a better quality of life. So
far, the larger study (accrual, 800 patients) has yielded equal durations of
progression-free survival for both the carboplatin and cisplatin combinations. If
future updates of these studies confirm the current results and show similar long
term survival, the combination of carboplatin area under the concentration-time
curve 5 or 6 plus paclitaxel 175 mg/m2 given over 3 hours is an attractive
regimen for the treatment of newly diagnosed epithelial ovarian cancer.
PMID- 10190787
TI - Paclitaxel plus carboplatin in the treatment of ovarian cancer.
AB - Two large, prospective randomized trials by the Gynecologic Oncology Group and
the European Organization for Research and Treatment of Cancer have demonstrated
the superiority of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton,
NJ)/cisplatin compared with cisplatin/cyclophosphamide in previously untreated
patients with advanced ovarian cancer. Patients receiving the paclitaxel
combination had a higher overall response rate, a longer time to disease
progression, and prolonged median survival. In an effort to reduce toxicity,
investigators developed combinations of carboplatin/paclitaxel that were found by
phase I/II trials to have activity comparable to cisplatin/paclitaxel but with
less toxicity. Prospective randomized trials of paclitaxel/cisplatin versus
paclitaxel/carboplatin were completed by the Gynecologic Oncology Group and by
European investigators and preliminary results identify no differences in
efficacy. Clinical trials of new combinations of paclitaxel/carboplatin with oral
etoposide, gemcitabine, or epirubicin have recently begun. Additional studies of
high-dose chemotherapy regimens of paclitaxel/carboplatin in untreated patients
with optimal stage III ovarian cancer also are in progress. The Gynecologic
Oncology Group has completed a randomized comparison of three versus six cycles
of paclitaxel/carboplatin in early stage disease. This study will be followed by
a trial in which all patients with poor-prognosis, early stage ovarian cancer
receive three cycles of paclitaxel/carboplatin followed by randomization to no
further treatment or to weekly paclitaxel. The combination of
paclitaxel/carboplatin is currently the preferred regimen for the treatment of
ovarian cancer.
PMID- 10190788
TI - Carboplatin and paclitaxel, alone and in combination: dose escalation,
measurement of renal function, and role of the p53 tumor suppressor gene.
AB - In this pharmacokinetic and dose-escalation study of the carboplatin/paclitaxel
(Taxol; Bristol-Myers Squibb Company, Princeton, NJ) combination, patients were
randomly assigned to receive paclitaxel either as a 1-hour or a 3-hour infusion.
The 1-hour infusion was feasible, with maximum tolerated doses similar to those
previously reported for a 3-hour infusion. Using patients' age, height, plasma
creatinine, and plasma creatine kinase provided an improved estimate of the
glomerular filtration rate compared with the more traditional creatinine-based
formulas according to population analysis of data derived from glomerular
filtration rate estimates performed by an isotope method. Studies of the p53 gene
sequence of ovarian tumors at diagnosis suggest that p53 mutations are a potent
predictor of response to subsequent treatment with carboplatin.
PMID- 10190789
TI - Paclitaxel-based chemotherapy for recurrent and/or metastatic head and neck
squamous cell carcinoma: current and future directions.
AB - Head and neck squamous cell carcinoma (HNSCC) is a devastating tumor, with
enormous repercussions both for the medical system and for the individual
patient. Functional and cosmetic morbidity are inherent in head and neck cancer
and its treatment, and the economic costs associated with the aggressive therapy
needed to battle the disease are substantial. Even with aggressive standard local
therapy (surgery and/or radiotherapy), the tumor recurs in approximately 60% of
patients with primary disease and the prognosis for those whose disease recurs or
metastasizes is poor. In light of these facts, trials of new therapy for
recurrent and/or metastatic HNSCC must focus on prolonging survival, improving
quality of life, and increasing convenience. The introduction in the 1990s of
newer agents such as ifosfamide and the taxanes (paclitaxel [Taxol; Bristol-Myers
Squibb Company, Princeton, NJ] and docetaxel) offers hope that these goals can be
achieved. All are active against HNSCC and the taxanes, in particular, appear
likely to be the most active single agents yet for treating recurrent and/or
metastatic HNSCC. This report reviews experience with paclitaxel-based treatment
regimens in HNSCC.
PMID- 10190790
TI - Paclitaxel in the treatment of esophageal cancer.
AB - Since its introduction, paclitaxel (Taxol; Bristol-Myers Squibb Company,
Princeton, NJ) has demonstrated significant antitumor activity in epidermoid
carcinomas and adenocarcinomas originating in the esophagus. Paclitaxel is the
most active single agent available to treat metastatic esophageal cancer.
Combinations of paclitaxel and cisplatin enhance response rates, but the addition
of 5-fluorouracil to this combination only increases toxicity without notably
augmenting clinical benefit. Paclitaxel also has been incorporated into numerous
preoperative regimens for patients with potentially resectable esophageal cancer.
While the optimal use of this agent remains undefined in the postoperative
setting, it is clear that paclitaxel will be incorporated into the next
generation of preoperative chemotherapy or combined chemotherapy plus
radiotherapy regimens for operable esophageal cancer.
PMID- 10190791
TI - Paclitaxel in the treatment of hormone-refractory prostate cancer.
AB - Prostate cancer is the most frequently diagnosed cancer and the second leading
cause of cancer death in men in the United States. In 1997 it was estimated that
more than 41,000 men died of this disease. Treatment of metastatic disease
remains palliative, with androgen ablation used as first-line therapy. After
failure of androgen ablation, chemotherapy can now be used to induce a remission
in many men. Treatment regimens that include paclitaxel (Taxol; Bristol-Myers
Squibb Company, Princeton, NJ) have been particularly successful in treating
hormone-refractory prostate cancer in the phase II setting. We have conducted a
trial of estramustine 280 mg orally three times per day for 14 days combined with
etoposide 50 mg/m2/d (in general, one 50-mg tablet twice a day) for 14 days, with
paclitaxel 135 mg/m2 over 1 hour on day 2. This regimen is repeated every 21 days
for a maximum of six cycles. Patients responding to therapy are then given a
break and re-treated at physician discretion. On preliminary analysis, 24 of 38
patients demonstrated a decline in pretreatment prostate-specific antigen of more
than 50% (63%). The regimen was well-tolerated and only seven patients
demonstrated grade 3 or 4 neutropenia. Further analysis is ongoing.
PMID- 10190792
TI - Overcoming bcl-2- and p53-mediated resistance in prostate cancer.
AB - Most prostate cancers eventually develop resistance to hormonal therapy and
chemotherapies. Many mechanisms for resistance to chemotherapy have been
identified. Mutations or inactivation of the p53 suppressor gene and
overexpression of bcl-2 are among such mechanisms. Mutations in the p53 gene can
lead to resistance to certain chemotherapy agents, and such mutations are seen
more often in metastatic than in primary prostate cancers. Thus, agents that are
active in the setting of mutated p53 may have some advantage in prostate cancer.
Overexpression of bcl-2 occurs frequently in prostate cancer and is associated
with both hormonal therapy and chemotherapy resistance. In experimental systems,
bcl-2 overexpression occurs after androgen deprivation and transfection of bcl-2
into sensitive cell lines makes them resistant to chemotherapy and hormonal
therapies. Bcl-2 can be inactivated by phosphorylation as occurs with taxanes.
The retinoids, as a class, can inhibit the growth of resistant cell lines that
overexpress bcl-2, and the combination of interferon (IFN) and cis-retinoic acid
(CRA) demonstrated increased antitumor activity. In our cell line model the
combination of IFN and CRA greatly enhanced the cytotoxicity of paclitaxel
(Taxol; Bristol-Myers Squibb Company, Princeton, NJ). Based on these
observations, we conducted a phase I/II trial of CRA and IFN-alpha in patients
with biochemical recurrence of prostate cancer. Twenty-six percent achieved a
decrease of prostate-specific antigen (PSA), which was correlated to elevated
serum transforming growth factor-beta. We then conducted a phase I trial of 13
CRA, IFN-alpha, and escalating doses of paclitaxel. Eighteen patients were
treated with 1 mg/kg CRA and 1x10(6) unit IFN on days 1 to 4 and paclitaxel at
doses from 100 to 175 mg/m2. Eleven patients received the 175 mg/m2 paclitaxel
dose. Two patients in the phase I study achieved partial responses (one cervix
and one prostate cancer). We subsequently initiated a phase II study of 13-CRA,
IFN-alpha, and paclitaxel in hormone refractory prostate cancer. For entry
patients must show progressive disease after androgen ablation. To test the
mechanism of action, we are assaying peripheral blood monocytes and, when
possible, tumor tissue for bcl-2 expression. As our understanding of the
mechanisms of tumor resistance to chemotherapy improves, we will be able to
design better approaches in treatment targeted to overcome the mechanisms of
resistance.
PMID- 10190793
TI - Review and outlook for the role of paclitaxel in urothelial carcinoma.
AB - Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is an active
agent in the treatment of patients with advanced urothelial carcinoma. The lack
of nephrotoxicity and the ability to administer this agent to select patients
with renal insufficiency provide potential advantages over the standard cisplatin
based regimens in this patient population. Paclitaxel-based combination regimens
have recently been developed and reported. Paclitaxel plus carboplatin is an
active and tolerable outpatient regimen for patients with advanced urothelial
cancer. Ongoing cooperative group trials will help to further define the activity
and toxicity of this regimen in previously untreated patients, patients with
prior treatment, and patients with abnormal renal function. A cooperative group
trial will compare paclitaxel plus carboplatin with the cisplatin-based regimen
cisplatin/ methotrexate/vinblastine/doxorubicin (MVAC). The role of paclitaxel in
the early disease and combined-modality settings in urothelial cancer remains to
be determined.
PMID- 10190794
TI - Paclitaxel-based treatment of lymphoma.
AB - The activity of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ)
recently was evaluated in patients with relapsed and refractory non-Hodgkin's
lymphoma in three phase II clinical trials using different doses and infusion
schedules. The largest trial, conducted at M.D. Anderson Cancer Center, used the
most intensive dose (200 mg/m2 infused over 3 hours every 3 weeks) in 96
patients. As expected, the response rate was low in patients with primary
refractory disease. In contrast, patients with intermediate-grade lymphoma and no
primary refractory disease had a response rate of 50% and those with low-grade
lymphoma had a response rate of 31%. Lower response rates were reported in
clinical trials conducted by the National Cancer Institute, which used paclitaxel
140 mg/m2 infused over 96 hours, and by the Southwest Oncology Group, which used
paclitaxel 175 mg/m2 infused over 24 hours. Paclitaxel-based combination programs
currently are being evaluated at M.D. Anderson Cancer Center and other
institutions in patients with relapsed non-Hodgkin's lymphoma. Early results are
encouraging.
PMID- 10190795
TI - The evolving role of paclitaxel for patients with carcinoma of unknown primary
site.
AB - Patients with carcinoma of unknown primary site represent a very heterogeneous
clinicopathologic group. Progress has been made in defining important clinical
subsets, and specialized pathologic analysis is essential for the poorly
differentiated neoplasms. Paclitaxel (Taxol; Bristol-Myers Squibb Company,
Princeton, NJ) is a broad-spectrum antineoplastic agent with demonstrated
activity in a wide variety of carcinomas. We have combined paclitaxel with
carboplatin and oral etoposide for the therapy of patients with unknown primary
carcinoma. The overall response rate (47%, with 13% complete responders) compares
favorably with any other chemotherapy. Furthermore, the median survival of 13.4
months was notable and encouraging. Toxicity was well-tolerated and no treatment
related deaths occurred. Additional data are needed to more firmly establish the
role of paclitaxel for unknown primary cancer.
PMID- 10190796
TI - Otolaryngologists older than 60 years: results of and reflections on survey
responses from 865 colleagues regarding retirement.
PMID- 10190797
TI - Acupuncture as a treatment for temporomandibular joint dysfunction: a systematic
review of randomized trials.
AB - OBJECTIVE: To summarize the data from randomized controlled trials of acupuncture
for temporomandibular joint dysfunction. METHODS: Four independent computerized
literature searches were performed. Only randomized trials were admitted in which
acupuncture was tested vs sham acupuncture, standard therapy, or no treatment at
all. Data were extracted in a predefined, standardized fashion. RESULTS: Six
reports met the inclusion and exclusion criteria, representing 3 distinct trials.
Overall, their results suggest that acupuncture might be an effective therapy for
temporomandibular joint dysfunction. However, none of the studies was designed to
control for a placebo effect. CONCLUSION: Even though all studies are in
accordance with the notion that acupuncture is effective for temporomandibular
joint dysfunction, this hypothesis requires confirmation through more rigorous
investigations.
PMID- 10190798
TI - IGF-1 gene transfer into denervated rat laryngeal muscle.
AB - OBJECTIVES: To demonstrate gene transfer in rat laryngeal muscle using a reporter
gene, beta-galactosidase, and a muscle-specific expression system containing the
human IGF-1 (hIGF-1) gene sequence and to investigate the myotrophic and
neurotrophic effects of hIGF-1 gene transfer in denervated rat laryngeal muscle.
METHODS: In 8 adult rats, a polyvinyl-based formulation containing beta
galactosidase DNA was injected into denervated thyroarytenoid muscle. Twelve
animals were similarly administered a polyvinyl-based formulation containing a
muscle-specific expression system and hIGF-1 DNA. Twelve animals were injected
with isotonic sodium chloride solution, and all animals survived for 1 month. The
production of beta-galactosidase and hIGF-1 was detected using
immunohistochemical techniques. The effects of hIGF-1 on motor endplates and
nerve sprouting were assessed using cholinesterase or silver staining and
immunostaining for growth-associated protein (GAP-43). mals by immunostaining, X
gal histochemical staining, or both. In frozen section specimens, hIGF-1
immunoreactivity was positive in 3 of 8 animals. In sequential sections, GAP-43
was localized to areas of hIGF-1 expression in 2 of the 3 hIGF-1-positive
specimens. Increased nerve sprouting and motor endplate contact occurred in 2 of
4 animals treated with hIGF-1. CONCLUSIONS: Gene transfer into laryngeal muscle
was demonstrated using a polyvinyl-based formulation containing a muscle-specific
gene expression system. Preliminary findings indicate a positive effect on motor
endplates, nerve sprouting, and the expression of GAP-43 in animals treated with
the hIGF-1 vector. This study establishes a foundation for investigating hIGF-1
gene transfer as a novel treatment of laryngeal paralysis. Further studies are
necessary to quantify myotrophic and neurotrophic effects and to establish
therapeutic benefit.
PMID- 10190799
TI - Recurrent gustatory sweating (Frey syndrome) after intracutaneous injection of
botulinum toxin type A: incidence, management, and outcome.
AB - OBJECTIVE: To evaluate the duration of effectiveness of intracutaneous injection
of botulinum toxin type A for gustatory sweating as well as the incidence,
severity, management, and outcome of recurrent gustatory sweating. DESIGN: An
inception cohort with a minimum of 18 months of follow-up. SETTING: A tertiary
care center and university teaching hospital. PATIENTS: Thirty-three patients
with severe gustatory sweating. INTERVENTION: Intracutaneous injection of 25 to
175 IU (mean, 86 IU) of botulinum toxin type A. MAIN OUTCOME MEASURES: Analysis
of the effectiveness of the intracutaneous injection of botulinum toxin type A
using the Kaplan-Meier actuarial life-table method; completion of the Minor
starch-iodine test in patients without symptomatic recurrent gustatory sweating;
and the patients' self-assessment of the severity of the recurrent gustatory
sweating. RESULTS: The 1-, 2-, and 3-year actuarial estimate for symptomatic
recurrent gustatory sweating was 27%, 63%, and 92%, respectively. In the 7
patients without symptomatic recurrent gustatory sweating, the Minor starch
iodine test revealed persistent gustatory sweating in 6, resulting in an overall
97% rate (32 of 33 patients) for recurrent gustatory sweating. No statistical
relationship could be demonstrated between the duration of effectiveness, the
incidence of recurrent gustatory sweating, the severity of recurrent gustatory
sweating, and the following variables: age, sex, cause of gustatory sweating,
skin surface involved, and dose of botulinum toxin type A injection. Within the
group of 26 patients with symptomatic recurrent gustatory sweating, (1) the
severity of the recurrent gustatory sweating was always reduced when compared
with the severity of the initial gustatory sweating, and (2) the recurrent
gustatory sweating always remained amenable to reinjection of botulinum toxin
type A. CONCLUSIONS: The present series demonstrated a linear regression in the
effectiveness of the intracutaneous injection of botulinum toxin type A in
patients with gustatory sweating, while no factors appeared to be statistically
related to the duration of effectiveness and/or the incidence of recurrent
gustatory sweating. However, because the severity of recurrent gustatory sweating
is reduced when compared with the severity of the initial gustatory sweating and
because recurrent gustatory sweating remains amenable to reinjection of botulinum
toxin type A, we believe that the intracutaneous injection of botulinum toxin
type A should become the first-line treatment option in patients with gustatory
sweating.
PMID- 10190800
TI - The long-term indwelling tracheoesophageal prosthesis for alaryngeal voice
rehabilitation.
AB - OBJECTIVE: To analyze the initial experience at Oregon Health Sciences
University, Portland, with the use of long-term indwelling tracheoesophageal
voice prostheses. DESIGN: Retrospective case series. SETTING: Tertiary referral
academic medical center. PATIENTS: Thirty patients undergoing speech
rehabilitation after laryngectomy during a period of 18 months. INTERVENTION:
Insertion of a long-term indwelling tracheoesophageal voice prosthesis. MAIN
OUTCOME MEASURES: Duration of use, complications. RESULTS: The mean duration of
placement for a single prosthesis was 4.9 months (148 days), with a range of 14
to 330 days. Sixteen of the 30 patients encountered problems with leakage because
of fungal colonization, the majority of which (15 of 16 cases) were solved with
either oral or topical application of nystatin. Size matching in terms of
prosthesis length and tract length was critical, and problems of this nature were
encountered in 11 of 30 patients. The incorporation of a second system of
prostheses that offered an increased number of size options solved these problems
in all of these patients. Ultimately, 27 of 30 patients were able to successfully
wear these prostheses. CONCLUSIONS: The indwelling tracheoesophageal voice
prosthesis offers patients all the advantages of tracheoesophageal speech
rehabilitation after laryngectomy without the inconvenience of frequent
prosthesis changes. With careful attention to the details of fitting and care, it
can be worn by the majority of patients successfully.
PMID- 10190801
TI - Unsurpassed reliability of free flaps for head and neck reconstruction.
AB - OBJECTIVE: To review the outcome and incidence of perioperative complications in
patients undergoing microvascular free flaps for reconstruction of the head and
neck region. DESIGN: A prospective case series. SETTING: An academic tertiary
care otolaryngology-head and neck surgery program. PATIENTS: One hundred fifteen
patients who underwent 119 consecutive free flaps performed by 1 surgeon during a
32-month period. INTERVENTIONS: Reconstruction primarily by means of radial
forearm, fibula, and rectus abdominis flaps (95% of the flaps selected for
reconstruction). MAIN OUTCOME MEASURE: The incidence of perioperative
reconstructive and medical complications. RESULTS: There was 1 perioperative
death (0.8%). Among the surviving patients, there was 1 case of complete flap
failure, resulting in an overall flap survival of 99.2%. There were 2 additional
cases (1.8%) of partial flap necrosis. Perioperative reconstructive complications
occurred during 10.1% of the hospitalizations, half of which required additional
surgical intervention. Notable perioperative medical complications occurred in
17.1% of the patients. CONCLUSIONS: Despite their reliance on small-vessel
anastomoses for survival, free flaps are extremely reliable with regard to the
incidence of flap necrosis, which contributes to a low incidence of perioperative
complications. Selection of flaps that have proven dependability contributes to a
successful outcome. While this technique frequently requires lengthy surgery in
an elderly patient population, the perioperative mortality) and morbidity are
acceptable. Because of their unsurpassed reliability, free flaps have become the
preferred method of reconstruction for most patients with major defects in the
head and neck region.
PMID- 10190802
TI - Predictive factors for neoplasia and malignancy in a neck mass.
AB - OBJECTIVE: To determine clinical factors that are able to predict the likelihood
of neoplasia and malignancy of cervical masses. DESIGN: Retrospective review of
case series. Data were collected for age, sex, a history of alcohol and tobacco
use, mass location, number, bilaterality, size, and duration. Logistic regression
was performed to determine which clinical variables were significant in a
prediction model for neoplasia and malignancy in a cervical mass. SETTING: An
academic general otolaryngology practice. RESULTS: Review of 160 open neck
biopsies yielded 95 complete cases for regression analysis. Thirty cases of
neoplasia (31.6%) and 12 cases of malignancy (12.6%) were noted. For the
prediction of neoplasia, logistic regression analysis identified patient age,
duration, and size of the mass to be statistically significant. The overall model
for neoplasia had positive and negative predictive values of 63.6% and 78.1%,
respectively, and an overall accuracy of 74.7%. For the prediction of malignancy,
only age was found to be significant. The model for malignancy failed to show any
classification utility beyond that of clinical judgment. CONCLUSIONS: On the
basis of clinical factors, a logistic regression model can distinguish patients
who have a low chance for neoplasia in a neck mass, and thereby help avoid
unnecessary biopsy. It is not as useful in selecting patients for early biopsy.
The strict prediction of malignancy on the basis of clinical variables alone is
difficult.
PMID- 10190803
TI - Practice patterns and clinical guidelines for posttreatment follow-up of head and
neck cancers: a comparison of 2 professional societies.
AB - OBJECTIVES: To determine and compare the current follow-up practice patterns of
members of 2 professional societies of head and neck surgeons, and to compare
these with the societies' published clinical practice guidelines. DESIGN: A
survey was mailed to the 640 members of the American Society for Head and Neck
Surgery (ASHNS); results were compared with those of a similar survey of the 824
members of the Society of Head and Neck Surgery (SHNS) and with the clinical
practice guidelines of the consensus committee of both societies. MAIN OUTCOME
MEASURES: Data were collected regarding the frequency of follow-up visits after
potentially curative resection of head and neck epidermoid carcinoma and the
types of diagnostic studies performed at each visit. RESULTS: A total of 318
ASHNS members responded to 1 of the mailings (49.7%), of which 280 responses
(43.8%) were evaluable. Most surgeons relied on directed history, physical
examination, and routine chest radiograph at varying intervals for detection of
recurrences and second primary tumors. Other tests were used sporadically. For
frequency of follow-up testing, the percentage of surgeons who followed the
published guidelines varied from 97% in postoperative year 1 to 62% in
postoperative year 5. A mean of 24% of surgeons varied from the guidelines in
their use of chest radiographs, and 45% varied in their use of liver function
tests. The ASHNS members used significantly more office visits than the SHNS
members during the first 2 postoperative years. CONCLUSIONS: The strategies used
by members of the ASHNS and the SHNS for posttreatment surveillance after
potentially curative resection of malignant neoplasms of the head and neck were
generally similar but showed some important differences. Most surgeons used
directed history and physical examination at regular intervals, and annual chest
radiographs. The follow-up practices of most members of these societies, which
have recently merged, fall within the recommendations of the Clinical Guidelines
Task Force.
PMID- 10190804
TI - Effect of functional endoscopic sinus surgery on bronchial asthma outcomes.
AB - BACKGROUND: For more than 70 years, the coexistence of asthma and paranasal
rhinosinusitis has been noted in the medical literature. Causal relationships
have been proposed but not proved. To date, limited evidence exists suggesting
that asthma improves after surgical correction of rhinosinusitis. OBJECTIVE: To
determine whether asthma control improved after first-time functional endoscopic
sinus surgery (FESS). PATIENTS AND METHODS: A retrospective medical record
analysis was performed on 13 patients with chronic bronchial asthma who underwent
FESS for medically refractory chronic rhinosinusitis. Patients received
comprehensive asthma care before and after FESS (mean, 19.3 and 33.1 months,
respectively). Outcomes analyzed included pre- and post-FESS individual and group
mean asthma symptom scores, medication use scores, pulmonary function test
results, and emergency department visits or hospital admissions for asthma.
Patient medical records were obtained from a private allergy-immunology practice
affiliated with a medical school. The surgical procedure was performed at a
tertiary care teaching hospital by a single ear, nose, and throat surgeon (R.L.).
RESULTS: Following FESS, there was no statistically significant change in group
mean asthma symptom scores, asthma medication use scores, pulmonary function test
results, and the number of emergency department visits or hospital admissions.
Only a few patients demonstrated statistically significant improvement after FESS
in asthma symptom scores (1 patient), medication use scores (1 patient), or
pulmonary function test results (2 patients). CONCLUSIONS: The data do not
support the hypothesis that first-time FESS for medically refractory chronic
rhinosinusitis in adult patients with chronic asthma leads to reduced
postoperative asthma symptoms or asthma medication use or improved pulmonary
function. Based on this limited study, a reexamination of the benefits of sinus
surgery to coexisting asthma is in order.
PMID- 10190806
TI - Management of distal tracheal stenosis.
AB - OBJECTIVE: To evaluate the treatment, perioperative management, and outcome of
infants who underwent repair of congenital tracheal stenosis. We hypothesized
that early resection and tracheoplasty with early weaning of ventilatory support
results in less mucosal injury, and thus better outcome. DESIGN: Retrospective
study from 1986 to 1996. SETTING: Tertiary care children's hospital. PATIENTS:
Seventeen consecutive infants with congenital tracheal stenosis, aged from birth
to 16 months. Fifteen patients had complete tracheal rings, 6 of whom also had a
left pulmonary artery sling. Fourteen patients underwent either tracheoplasty or
resection and reanastomosis of the trachea, both facilitated by cardiopulmonary
bypass. RESULTS: Six patients underwent resection and reanastomosis; 4 patients
were extubated within 2 to 5 days without sequelae. There was 1 unrelated
perioperative death. Two patients required reintubation. Eight patients required
tracheoplasty due to severe tracheal stenosis and had variable postoperative
courses. Seven of 14 patients required 0 to 1 postoperative bronchoscopies. Seven
of 14 patients required 2 to 7 bronchoscopies for granulation tissue formation,
cicatrix, graft collapse, and tracheitis. One patient required numerous
procedures and revision tracheoplasty for cicatrix and stenosis. CONCLUSIONS:
Correction of short-segment (<5 rings) tracheal stenosis by resection and
reanastomosis of the trachea with the aid of cardiopulmonary bypass and early
weaning of ventilatory support is recommended. Tracheoplasty using either the
castellation technique or slide tracheoplasty is recommended in the treatment of
infants with severe (long segment) tracheal stenosis.
PMID- 10190805
TI - Single-stage laryngotracheal reconstruction: the Great Ormond Street experience
and guidelines for patient selection.
AB - OBJECTIVES: To review all patients undergoing single-stage laryngotracheal
reconstruction and to determine guidelines to predict successful outcomes and
prevent the necessity of tracheotomy following laryngotracheal reconstruction.
DESIGN: Chart review. SETTING: Tertiary care children's hospital. PATIENTS: A
retrospective chart review was performed at our institution involving all
patients who underwent single-stage laryngotracheal reconstruction from 1993
through 1996. A total of 28 patients were reviewed. RESULTS: Based on this chart
review, a statistically higher incidence of extubation complications (P = .045),
ie, bleeding, reintubation, or subcutaneous emphysema, occurred in children who
weighed less than 4 kg. Although not statistically significant (P>.99), the
relative risks of failure, defined as tracheotomy dependent or significant airway
compromise following single-stage laryngotracheal reconstruction, were 3.43 if
the child's weight was less than 4 kg at the time of surgery and 2.31 if the
gestational age was less than 30 weeks at the time of surgery. Length of time for
intubation did not appear to have any effect on outcome. CONCLUSIONS: Patients'
gestational age and weight at the time of surgery appear to have the most impact
on successful outcome. Children weighing more than 4 kg and those with
gestational age of greater than 30 weeks appear to have a greater chance at
successful extubation and eventual patent airway. Duration of intubation
following single-stage laryngotracheal reconstruction does not appear to affect
outcome.
PMID- 10190807
TI - Avoidance of primary post-tonsillectomy hemorrhage in a teaching program.
AB - OBJECTIVE: To determine the incidence of primary post-tonsillectomy hemorrhage in
a teaching institution by using a uniform technique, including a 3-minute
relaxation of retraction before case termination and the use of bismuth
subgallate. DESIGN: Case series. SETTING: Tertiary care academic pediatric
center. PATIENTS: A 7-year retrospective study was performed by using the medical
records of 1286 children without a bleeding abnormality who underwent
tonsillectomy (with or without adenoidectomy). A uniform technique, proposed to
reduce hemorrhage, was used for 705 children and was not used for 581 children.
RESULTS: No episodes of primary hemorrhage (onset < or = 24 hours after surgery)
occurred, and the incidence of delayed hemorrhage (onset >24 hours after surgery)
was 1.1% in the study group. The primary hemorrhage rate of the study group was
significantly lower (P = .007) than the rate for the reference group (0.0% vs
1.0%), as was the total hemorrhage rate (1.1% vs 4.1%) and the delayed hemorrhage
rate (1.1% vs 3.1%). CONCLUSION: A uniform technique including the use of bismuth
subgallate and reassessment of the tonsillar fossae after a 3-minute observation
period reduces the incidence of primary tonsillar hemorrhage in a teaching
institution setting.
PMID- 10190808
TI - Ofloxacin otic solution in patients with otitis media: an analysis of drug
concentrations.
AB - OBJECTIVE: To measure the concentration of ofloxacin in otorrhea, serum, and
middle ear mucosa after topical administration of 0.3% ofloxacin otic solution.
DESIGN: Study of 0.3% ofloxacin otic solution administered in a single dose of
0.5 mL in adults or 0.25 mL in children with chronic suppurative otitis media and
perforated tympanic membrane, with serial sampling of otorrhea and serum up to 8
hours after dosing and middle ear mucosa up to 2 hours after dosing. SETTING:
Three hospitals in Kagoshima, Japan. PATIENTS: Thirty-eight patients (age range,
3-81 years) with chronic suppurative otitis media and perforated tympanic
membrane; 20 patients had sampling of otorrhea and serum and 18 patients (who
required middle ear surgery) had middle ear mucosa and serum sampling. RESULTS:
High concentrations of ofloxacin were measured in otorrhea samples taken
immediately after dosing, followed by a rapid, nonlogarithmic decline.
Elimination of the drug through otorrhea was believed to be related to loss from
the application site with ear drainage, rather than to biologic mechanisms.
Maximum concentration of ofloxacin in otorrhea was seen at the initial sampling
time, 30 minutes after dosing, with concentrations measured up to the last
sampling at 8 hours. Very low concentrations of ofloxacin were found in serum
after topical administration of the drug. Concentrations were not detected in
serum samples of most of the patients. The highest concentration measured was 10
ng/mL. Drug concentrations were detected primarily in samples obtained up to 1
hour after the dose was administered. Mucosal drug concentrations were highly
variable, ranging from nondetectable to 602 pg/g. For the 6 bacterial strains
isolated from the middle ear, the highest minimum inhibitory concentration of
ofloxacin was covered by otorrhea drug concentrations measured at up to 8 hours
after dosing in some patients. No adverse events were observed. No clinically
significant adverse changes in laboratory test results or audiometric results
were observed. CONCLUSIONS: Drug concentrations were high in otorrhea, very low
or not detected in serum, and highly variable in middle ear mucosa. Nonbiologic
loss of the drug with the ear drainage through the external auditory canal and
eustachian tube was probably related to the high concentration in otorrhea
samples. Drug concentrations in middle ear mucosa suggest that the drug reaches
the infection site.
PMID- 10190809
TI - Vestibular function in children with the CHARGE association.
AB - BACKGROUND: Histopathological examinations and computed tomographic scans of the
temporal bone in patients with the CHARGE association (a malformative syndrome
that includes coloboma, heart disease, choanal atresia, retarded development,
genital hypoplasia, and ear anomalies, including hypoplasia of the external ear
and hearing loss) have shown an absence of semicircular canals and a Mondini form
of cochlear dysplasia. Until recently, no information was available concerning a
possible loss of vestibular function, which could be a factor in retarded
posturomotor development. To our knowledge, this is the first report of otolith
tests done on patients with the CHARGE association. OBJECTIVE: To test residual
vestibular function in patients with the CHARGE association. STUDY DESIGN: In 7
patients with the CHARGE association, we made electro-oculographic recordings of
vestibulo-ocular responses to earth-vertical and off-vertical axis rotations to
evaluate the function of the canal and the otolith-vestibular systems. RESULTS:
None of the 7 patients had semicircular canals in the computed tomographic scan,
and none had canal vestibulo-ocular responses to earth-vertical axis rotation,
but all had normal otolith vestibulo-ocular responses to the off-vertical axis
rotation test. CONCLUSIONS: These results support the hypothesis of a residual
functional otolith organ in the hypoplastic posterior labyrinth of children with
the CHARGE association. The severe delays in psychomotor development presented by
these children are more likely a consequence of multiple factors: canal
vestibular deficit, visual impairment, and environmental conditions (long
hospital stays and breathing and feeding problems). The remaining sensitivity of
the otolith system to gravity and linear acceleration forces in these children
could be exploited in early education programs to improve their posturomotor
development.
PMID- 10190810
TI - Imaging quiz case 1. Solitary plasmacytoma of the sternum with soft tissue
extension.
PMID- 10190811
TI - Imaging quiz case 2. Osteoma of the mastoid antrum and cholesteatoma.
PMID- 10190812
TI - Evaluation of obstructive sleep apnea by polysomnography prior to pediatric
adenotonsillectomy.
PMID- 10190813
TI - The diagnosis of OSAS and UARS in children: trying to relieve the frustration.
PMID- 10190814
TI - Clinical opinion: preoperative sleep studies.
PMID- 10190815
TI - Mutational analysis and the pathogenesis of variant X-linked adrenoleukodystrophy
phenotypes.
PMID- 10190816
TI - Multiple sclerosis: therapeutic update.
AB - Therapy for multiple sclerosis (MS) is undergoing rapid changes. We discuss
recent developments in the therapy of MS, failures as well as successes, and
consider some newer approaches. Multiple sclerosis, a multifocal, initially
remitting-relapsing, and in some cases primarily progressive, inflammatory
central nervous system immune-mediated demyelinating disease, with some axonal
involvement, is currently the most common disabling neurologic disease of young
people in North America and Europe. Although much is known about the
pathogenesis, there is no cure and the disease must be managed long-term.
Recently, there have been a number of advances in the treatment of MS.
PMID- 10190817
TI - Biomarkers of Alzheimer disease.
AB - A definitive diagnosis of Alzheimer disease (AD) depends on finding widespread
neurofibrillary tangles and plentiful neuritic plaques in the brain of an
individual with a clinical diagnosis of progressive dementia. Using contemporary
diagnostic criteria, the antemortem diagnosis of probable AD in centers
specialized for AD is confirmed 80% to 90% of the time. There is the suspicion,
but no firm data, that diagnostic accuracy is much lower outside of practices
dedicated to patients with dementia. Furthermore, the diagnostic workup is
expensive. In most settings, the evaluation generally includes a careful medical
history and physical examination; neurologic examination (and psychiatric
consultation as indicated); laboratory blood studies to exclude underlying
metabolic and medical illnesses that masquerade as AD; a mental status assessment
and formal cognitive tests; and a computed tomographic scan or magnetic resonance
imaging of the brain. Because these procedures are time-consuming and costly,
there is a need to identify biological tests that can circumvent aspects of this
workup and point the physician to the correct diagnosis. It would be highly
desirable to measure a substance or substances in blood or urine samples or
cerebrospinal fluid (CSF) that would lead to a positive diagnosis of AD without
the need for specialized dementia clinics and the expense and time of standard
diagnostic evaluations. In response to this need, the Reagan Research Institute
of the Alzheimer's Association and the National Institute on Aging convened a
working group in 1997 to examine the status of various antemortem markers for AD.
The consensus statement of this group, entitled "Molecular and Biochemical
Markers of AD," was published in 1998. The consensus statement first defined the
characteristics of an ideal biomarker, and then outlined the steps required for a
proposed biomarker to achieve acceptance by the medical community. Finally, the
statement reviewed the current state of all proposed biological markers. The
workshop participants observed that none of the current biomarkers had yet
achieved universal acceptance and concluded none fully met the consensus criteria
for an ideal marker. Nonetheless, several tests were identified as good markers
for familial AD, and several other tests showed promise as a diagnostic aid for
sporadic AD. The purpose of this review is to put these recommendations into a
practical context. What does the consensus statement tell the practicing
clinician? How do the opinions in the consensus statement affect clinical
practice in diagnosing and treating patients with dementia?
PMID- 10190818
TI - Gene therapy in the central nervous system: the use of recombinant retroviruses.
AB - Only a handful of the hundreds of known vertebrate retroviruses have been
deliberately subverted for use as carriers of recombinant genetic material.
Retroviruses receive their name from the fact that their genome undergoes
conversion from RNA to DNA following infection of a host cell. Also
characteristic of retroviruses and uncommon for most other types of viruses is
that the genome of the retrovirus integrates itself permanently into the DNA of
the host cell. Once integrated into the host genome, the inserted provirus acts
as a factory for producing more retroviral RNA genomes and expressing retroviral
packaging proteins. Both components combine to form viral particles that bud from
the surface of the infected cells.
PMID- 10190819
TI - Mutational analysis and genotype-phenotype correlation of 29 unrelated Japanese
patients with X-linked adrenoleukodystrophy.
AB - BACKGROUND: X-linked adrenoleukodystrophy (ALD) is an inherited disease
characterized by progressive neurologic dysfunction, occasionally associated with
adrenal insufficiency. The classic form of ALD usually has onset in childhood
(childhood cerebral ALD), with rapid neurologic deterioration leading to a
vegetative state. Adult-onset cerebral ALD also presents with rapidly progressive
neurologic dysfunction. Milder phenotypes such as adrenomyeloneuropathy and
Addison disease only also have been recognized. Despite discovery of the
causative gene, a molecular basis for the diverse clinical presentations remains
to be elucidated. OBJECTIVES: To conduct mutational analyses in 29 Japanese
patients with ALD from 29 unrelated families, to obtain knowledge of the spectrum
of mutations in this gene, and to study genotype-phenotype correlations in
Japanese patients. METHODS: The 29 patients comprised 13 patients with childhood
cerebral ALD, 11 patients with adult-onset cerebral ALD, and 5 patients with
adrenomyeloneuropathy. We conducted detailed mutational analyses of 29 unrelated
Japanese patients with ALD by genomic Southern blot analysis and direct
nucleotide sequence analysis of reverse transcriptase-polymerase chain reaction
products derived from total RNA that was extracted from cultured skin
fibroblasts, lymphoblastoid cells, or peripheral blood leukocytes. RESULTS: Three
patients with adult-onset cerebral ALD were identified as having large genomic
rearrangements. The remaining 26 patients were identified as having 21
independent mutations, including 12 novel mutations resulting in small nucleotide
alterations in the ALD gene. Eighteen (69%) of 26 mutations were missense
mutations. Most missense mutations involved amino acids conserved in homologous
gene products, including PMP70, mALDRP, and Pxa1p. The AG dinucleotide deletion
at position 1081-1082, which has been reported previously to be the most common
mutation in white patients (12%-17%), was also identified as the most common
mutation in Japanese patients (12%). All phenotypes were associated with
mutations resulting in protein truncation or subtle amino acid changes. There
were no differences in phenotypic expressions between missense mutations
involving conserved amino acids and those involving nonconserved amino acids.
CONCLUSIONS: There are no obvious correlations between the phenotypes of patients
with ALD and their genotypes, suggesting that other genetic or environmental
factors modify the phenotypic expressions of ALD.
PMID- 10190820
TI - Mild cognitive impairment: clinical characterization and outcome.
AB - BACKGROUND: Subjects with a mild cognitive impairment (MCI) have a memory
impairment beyond that expected for age and education yet are not demented. These
subjects are becoming the focus of many prediction studies and early intervention
trials. OBJECTIVE: To characterize clinically subjects with MCI cross-sectionally
and longitudinally. DESIGN: A prospective, longitudinal inception cohort.
SETTING: General community clinic. PARTICIPANTS: A sample of 76 consecutively
evaluated subjects with MCI were compared with 234 healthy control subjects and
106 patients with mild Alzheimer disease (AD), all from a community setting as
part of the Mayo Clinic Alzheimer's Disease Center/Alzheimer's Disease Patient
Registry, Rochester, Minn. MAIN OUTCOME MEASURES: The 3 groups of individuals
were compared on demographic factors and measures of cognitive function including
the Mini-Mental State Examination, Wechsler Adult Intelligence Scale-Revised,
Wechsler Memory Scale-Revised, Dementia Rating Scale, Free and Cued Selective
Reminding Test, and Auditory Verbal Learning Test. Clinical classifications of
dementia and AD were determined according to the Diagnostic and Statistical
Manual of Mental Disorders, Revised Third Edition and the National Institute of
Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and
Related Disorders Association criteria, respectively. RESULTS: The primary
distinction between control subjects and subjects with MCI was in the area of
memory, while other cognitive functions were comparable. However, when the
subjects with MCI were compared with the patients with very mild AD, memory
performance was similar, but patients with AD were more impaired in other
cognitive domains as well. Longitudinal performance demonstrated that the
subjects with MCI declined at a rate greater than that of the controls but less
rapidly than the patients with mild AD. CONCLUSIONS: Patients who meet the
criteria for MCI can be differentiated from healthy control subjects and those
with very mild AD. They appear to constitute a clinical entity that can be
characterized for treatment interventions.
PMID- 10190821
TI - Elevated levels of antibody to myelin oligodendrocyte glycoprotein is not
specific for patients with multiple sclerosis.
AB - OBJECTIVE: To evaluate the presence and specificity of anti-myelin
oligodendrocyte glycoprotein (MOG) antibody in the cerebrospinal fluid and plasma
of patients with multiple sclerosis (MS). DESIGN: Case-control study of patients
with clinically definite MS compared with patients with other neurologic diseases
(ONDs) of the central nervous system and control subjects. SETTING: Referral
center in the Department of Neurology of Hadassah University Hospital, greater
Jerusalem area, Israel. PARTICIPANTS: Consecutive cerebrospinal fluid samples
from 31 patients with MS, 31 patients with ONDs, and 28 healthy controls; and
plasma samples from 33 patients with MS, 28 patients with ONDs, and 31 healthy
controls were taken from the cerebrospinal fluid and plasma bank of the
Department of Neurology, Hadassah University Hospital. MAIN OUTCOME MEASURES:
Levels and frequencies of anti-MOG antibody in patients with MS, as defined by
enzyme-linked immunosorbent assay. RESULTS: Cerebrospinal fluid levels of
antibodies to MOG and to myelin basic protein were significantly higher in
patients with MS (P<.001 and P = .001, respectively) and patients with ONDs (P =
.005 and P = .03, respectively) compared with controls; frequency of antibodies
to MOG, but not to myelin basic protein, was higher in patients with MS and
patients with ONDs (P = .01 and P = .003, respectively, for the frequency of anti
MOG antibody, and P = .65 and P = .41, respectively, for the frequency of anti
myelin basic protein antibody). Plasma levels of antibodies to MOG and to myelin
basic protein were higher in patients with MS compared with patients with ONDs (P
= .003 for both comparisons) and with controls (P = .03 and P = .04,
respectively); however, the frequency of antibodies to MOG and myelin basic
protein was similar in patients with MS, patients with ONDs (P=.54 and P = .82,
respectively), and controls (P = .50 and P = .14, respectively). CONCLUSIONS: The
elevated presence of anti-MOG antibody is not specific for MS because a similar
appearance was also demonstrated in patients with ONDs. Therefore, it is not
clear whether this antibody is pathogenic in MS or, on the contrary, has a
defensive role against further immune-mediated damage after myelin breakdown.
PMID- 10190822
TI - Neuropsychologic status in multiple sclerosis after treatment with glatiramer.
AB - BACKGROUND: Glatiramer acetate (Copaxone) therapy reduces clinical disease
activity in relapsing-remitting multiple sclerosis (MS). OBJECTIVE: To study the
effect of glatiramer therapy on neuropsychologic function as part of a
randomized, placebo-controlled, multicenter trial. METHODS: Two hundred forty
eight patients with relapsing-remitting MS and mild to moderate disability
(Expanded Disability Status Scale score, <5.0) were tested before and 12 and 24
months after randomization to administration of glatiramer acetate, 20 mg/d, or
matching placebo. Neuropsychologic tests examined 5 cognitive domains most often
disrupted in patients with MS: sustained attention, perceptual processing, verbal
and visuospatial memory, and semantic retrieval. RESULTS: Baseline
neuropsychologic test performance was similar in both treatment groups and was
within normal range, except for impaired semantic retrieval. Mean
neuropsychologic test scores were higher at 12 and 24 months than at baseline,
and no differences were detected between treatment groups over time. No
significant interactions were detected between treatment and either time or
baseline impairment. CONCLUSIONS: Our 2-year longitudinal study showed no effect
of glatiramer therapy on cognitive function in relapsing-remitting MS. Although
it is possible that glatiramer therapy has no effect on cognitive function, the
lack of measurable decline in cognitive function in both patient groups for 2
years limits the opportunity for glatiramer to demonstrate a therapeutic effect
by minimizing such decline. Emerging treatments for MS should continue to be
examined for their effect on cognitive impairment because it can be a critical
determinant of disability. A greater understanding of the natural history of
cognitive decline in MS is essential for a rational design of these drug trials.
PMID- 10190823
TI - Brain proton magnetic resonance spectroscopy and brain atrophy in myotonic
dystrophy.
AB - OBJECTIVES: To evaluate by magnetic resonance spectroscopy the age-related
cerebral alterations present in myotonic dystrophy (MD) and to compare these
results with those obtained by magnetic resonance imaging. DESIGN: Twenty-one
patients (aged 16-63 years) with MD were compared with 16 age-matched healthy
control subjects. RESULTS: In magnetic resonance spectroscopy, the mean (+/- SD)
ratio of N-acetylaspartate to creatine and phosphocreatine in the patients with
MD (1.09 +/- 0.32) was significantly lower than that in the control subjects
(1.93 +/- 0.43) (P<.001). The mean ratio of N-acetylaspartate to choline
containing compounds in the patients with MD (1.70 +/- 0.44) was also
significantly lower than that in the control subjects (2.75 +/- 0.53) (P<.001).
These changes could be observed already in the younger patients. In magnetic
resonance imaging, the mean brain area was significantly decreased and the mean
ventricular space was significantly increased in patients with MD compared with
the control subjects. Although we have confirmed brain atrophy in patients with
MD in previous reports, a regression analysis indicated that the brain shrinks
progressively with age in patients with this disorder and in control subjects,
resulting in overlapping values for younger subjects. CONCLUSION: Magnetic
resonance spectroscopy indicates that the cerebral abnormalities in patients with
MD may be present at an early stage, when the results of magnetic resonance
imaging studies are still equivocal.
PMID- 10190824
TI - Progression of parkinsonian signs in Parkinson disease.
AB - BACKGROUND: Current knowledge about the rate of progression of extrapyramidal
signs (EPSs) in Parkinson disease (PD) is derived largely from cross-sectional
studies comparing subjects at various stages of illness rather than longitudinal
studies in which the subjects were followed up over time. OBJECTIVE: To
longitudinally study the progression of EPSs in PD by quantifying the rate of
change of EPSs and by examining each EPS (rigidity, bradykinesia, tremor, and
postural instability) separately. METHODS: A community-based cohort of 237
patients with PD living in Washington Heights-Inwood in Manhattan, NY, was
evaluated at baseline and at yearly intervals. The EPSs were rated using the
motor portion of the Unified Parkinson's Disease Rating Scale Motor Examination.
Analyses of longitudinal data were performed by applying generalized estimating
equations to regression analyses. RESULTS: The total EPS score increased at an
annual rate of 1.5 points (1.5%), but, among those who died, the total EPS score
increased at an annual rate of 3.6 points (3.6%). Bradykinesia, rigidity, and
gait and balance subscores worsened at similar annual rates of 2.0% to 3.1%,
whereas the tremor subscore did not clearly worsen with time. Patients with a
shorter disease duration (< or =3 years) may have progressed more rapidly than
patients with longer disease duration (annual rate of change, 1.9% vs 1.4%,
respectively), although this did not reach statistical significance. A high total
EPS score was independently associated with dementia, low Activities of Daily
Living score, and long disease duration at baseline. CONCLUSIONS: In this cohort,
the progression of EPSs in PD occurred at a rate of 1.5% per year and at twice
that rate among those who died. Bradykinesia, rigidity, and gait and balance
impairment worsened at similar rates, whereas tremor did not, suggesting that
tremor may be relatively independent of these other cardinal manifestations of
PD.
PMID- 10190825
TI - Prefrontal gray and white matter volumes in healthy aging and Alzheimer disease.
AB - OBJECTIVES: To quantify the contribution of gray and white matter volumes to
total prefrontal volume in healthy aging. To determine if prefrontal tissue
volumes distinguish healthy aging from Alzheimer disease (AD). DESIGN: Volumes of
total prefrontal cortex, prefrontal gray matter, and prefrontal white matter were
compared among young healthy elderly (YHE) (n = 14; mean age, 70 years), old
healthy elderly (OHE) (n = 14; mean age, 90 years), and subjects with AD (n = 14;
mean age, 70 years) by analysis of variance. Additionally, Pearson correlations
were performed between volumes and age. RESULTS: Old healthy elderly and subjects
with AD had significantly less total prefrontal volume (approximately 15% less in
both groups) and prefrontal white matter volume (approximately 30% less and 20%
less in the OHE and AD groups, respectively) than YHE, but there were no
differences between the OHE and AD groups. There was a significant difference in
gray-white matter volume ratio with OHE having a higher ratio than YHE. Subjects
with AD did not differ from YHE or OHE in this ratio. There were significant
negative correlations between age and total prefrontal volume and age and
prefrontal white matter volume in the healthy subjects. CONCLUSIONS: In the very
old, the decline of white matter volume is disproportionately greater than the
decline of gray matter volume. In subjects with AD both gray and white matter
loss contribute to the decline of prefrontal volume. This is demonstrated by the
gray-white matter ratio that does not differ between YHE and subjects with AD.
Thus, it is likely that AD is different from accelerated aging.
PMID- 10190826
TI - Development of hypointense lesions on T1-weighted spin-echo magnetic resonance
images in multiple sclerosis: relation to inflammatory activity.
AB - OBJECTIVE: To evaluate whether degree of inflammatory activity in multiple
sclerosis, expressed by frequency of gadolinium enhancement, has prognostic value
for development of hypointense lesions on T1-weighted spin-echo magnetic
resonance images, a putative marker of tissue destruction. DESIGN: Cohort design
with long-term follow-up. Thirty-eight patients with multiple sclerosis who in
the past had been monitored with monthly gadolinium-enhanced magnetic resonance
imaging for a median period of 10 months (range, 6-12 months) were reexamined
after a median period of 40.5 months (range, 33-80 months). SETTING: Magnetic
Resonance Center for Multiple Sclerosis Research, Amsterdam, the Netherlands,
referral center. MAIN OUTCOME MEASURES: The new enhancing lesion rate (median
number of gadolinium-enhancing lesions per monthly scan) during initial monthly
follow-up; hypointense T1 and hyperintense T2 lesion load at first and last
visit. RESULTS: The number of enhancing lesions on entry scan correlated with the
new enhancing lesions rate (r = 0.64; P<.001, Spearman rank correlation
coefficient). The new enhancing lesion rate correlated with yearly increase in T1
(r = 0.42; P<.01, Spearman rank correlation coefficient) and T2 (r = 0.47; P<.01,
Spearman rank correlation coefficient) lesion load. Initial T1 lesion load
correlated more strongly with yearly increase in T1 lesion load (r = 0.68; P<.01,
Spearman rank correlation coefficient). CONCLUSIONS: Degree of inflammatory
activity only partially predicted increase in T1 (and T2) lesion load at long
term follow-up. Initial T1 lesion load strongly contributed to subsequent
increase in hypointense T1 lesion load, suggesting that there is a subpopulation
of patients with multiple sclerosis who are prone to develop destructive lesions.
PMID- 10190827
TI - The exercise test in Andersen syndrome.
AB - BACKGROUND: Andersen syndrome is a rare form of periodic paralysis (PP)
associated with dysmorphic features and potentially fatal cardiac dysrhythmias.
To date, no electrodiagnostic abnormalities have been reported that can be used
to confirm the presence of PP in this condition. OBJECTIVES: To determine if the
exercise test could be used to confirm the diagnosis of PP in Andersen syndrome.
To evaluate the exercise test as a means to assess neuromuscular status during
treatment. METHODS: We performed the exercise test on 2 patients with Andersen
syndrome. In 1 patient, we used a modified version of the test to document
responsiveness to treatment with tocainide. RESULTS: Studies in both patients
demonstrated a progressive decline in the compound muscle action potential
amplitude after exercise that was characteristic of the phenomenon seen in other
forms of PP. In 1 patient, improvement in interattack strength and a reduction in
the number of attacks of weakness correlated with improvement in the test
results. CONCLUSIONS: Our cases demonstrate that the exercise test can confirm
the diagnosis of PP in Andersen syndrome. A modified version of exercise testing
may also be considered as an objective method for documenting treatment responses
in PP.
PMID- 10190828
TI - Creutzfeldt-Jakob disease with florid-type plaques after cadaveric dura mater
grafting.
AB - BACKGROUND: Many reported cases of iatrogenic Creutzfeldt-Jakob disease (CJD)
developed after grafting cadaveric dura mater contaminated with CJD prions (dura
associated CJD). They are known to be clinicopathologically similar to sporadic
CJD. We report herein 2 autopsy cases of dura-associated CJD with atypical
clinicopathological features. PATIENTS: Two patients presented with progressive
ataxia and mental deterioration 10 or 11 years after neurosurgical treatment with
cadaveric dural grafting, which led to their deaths at 8 and 17 months,
respectively, after onset. RESULTS: The cases were clinically atypical in
exhibiting no or late occurrence of myoclonus and periodic synchronous discharges
on electroencephalographic studies. They were pathologically unique in several
aspects. The most striking feature was the presence of many prion protein (PrP)
plaques in multiple areas in the brain. Some of them were the "florid" type
surrounded by a zone of spongiform changes known to be a hallmark for the new
variant CJD. The distribution of spongiform degeneration was also unique in that
it was intense in the thalamus, basal ganglia, and the dentate nuclei of the
cerebellum but milder in the cerebrum. There were no mutations in the PrP gene of
the patients. There was no major difference in the size and glycoform pattern
between the abnormal isoform of PrP extracted from the brain tissue from the dura
associated cases of CJD and that from a sporadic case of CJD. CONCLUSIONS: These
2 cases are clinicopathologically distinct from typical dura-associated cases of
CJD. They may be a subtype with florid-type plaques in dura-associated CJD.
PMID- 10190829
TI - Neurofibromatosis type 1.
AB - Neurofibromatosis (NF) has perhaps been the most notorious of the neurocutaneous
disorders. Both Quasimoto of Victor Hugo's The Hunchback of Notre Dame and John
Merrick, known as the Elephant Man (who subsequently has been more properly
classified as having Proteus syndrome, a quite different disorder), are 2
infamous examples that have shaped many popular misconceptions about this
disease. Neurofibromatosis is now understood as a hamartomatous disorder on the
basis of molecular genetic studies. Studies on NF have been pivotal to
understanding the functions of oncogenes in tumorigenesis.
PMID- 10190830
TI - 20/20 vision.
PMID- 10190831
TI - Power analysis is emphasized too much in nursing research.
PMID- 10190832
TI - Adult emergency visits for chronic cardiorespiratory disease: does dyspnea
matter?
AB - BACKGROUND: Dyspnea is among the most common reasons for emergency department
(ED) visits, yet little is known about how it is associated with visit
characteristics and disposition or about how such associations differ across
diagnoses. OBJECTIVES: To characterize ED visits for chronic cardiorespiratory
diseases in which dyspnea is a prominent symptom. Visit demographics and
relations among reasons for presenting, visit urgency, medications, and visit
disposition were examined. METHODS: Data for this cross-sectional descriptive
exploratory study came from the 1992 National Hospital Ambulatory Medical Care
Survey. All adult ED visits in the dataset for asthma (n = 395), chronic
obstructive pulmonary disease (COPD; n = 239), and congestive heart failure (CHF;
n = 320), as well as for mixed and restrictive chronic lung diseases (n = 18 and
n = 14, respectively), were analyzed. RESULTS: Dyspnea was the most common reason
for ED visit across diagnoses, and was associated with an approximate twofold
increase in likelihood of admission for patients with COPD (odds ratio [OR] =
1.9, p < .04), and, controlling for age, CHF (OR = 1.7, p = .035). Dyspnea, alone
or controlling for age, did not significantly increase the likelihood of
admission for asthma. However, across all diagnoses, dyspnea was associated with
a two- to threefold increase in the likelihood of receiving intravenous (i.v.)
fluids (p < or = .006), whereas receiving an i.v. markedly increased the
likelihood of admission (OR = 10.0, p < .0001 for COPD; OR = 10.2, p < .0001 for
asthma; and OR = 3.8; p < .0001 for CHF). Age independently predicted admission
for asthma and CHF, but not COPD. The percentage of nonurgent visits resulting in
admission was markedly higher for COPD (19%) and CHF (41%) than for asthma (4%)
or adult visits in general (6%). CONCLUSIONS: Reports of dyspnea increased the
likelihood of admission from the ED either directly or indirectly, depending on
diagnosis. Judgments of nonurgency may be less dependable in ED visits for COPD
and CHF than for asthma or adult visits generally.
PMID- 10190834
TI - Physiological responses of preterm infants to breast-feeding and bottle-feeding
with the orthodontic nipple.
AB - BACKGROUND: Although the orthodontic nipple has been recommended for many years
to supplement breast-feeding infants, it is not known if this nipple is suitable
for hospitalized preterm infants whose mothers wish to breast-feed. OBJECTIVES:
To describe and compare short-term physiologic responses of preterm infants
serving as their own controls for two feeding methods, breast-feeding and bottle
feeding with the orthodontic nipple. METHOD: The sample consisted of eight
preterm infants, mean birth weight of 1,370 grams and mean gestational age at
birth of 30.2 weeks' gestation, who served as their own controls for breast- and
bottle-feeding sessions. The dependent variables, sucking, breathing, and oxygen
saturation, were measured noninvasively throughout breast- and bottle-feeding
sessions and recorded on a polygraph. Data were analyzed quantitatively and
qualitatively for 14 breast-feeding sessions and 15 bottle-feeding sessions.
RESULTS: Statistically significant differences were found in that infants
breathed more during sucking bursts for breast-feeding sessions when compared to
bottle-feeding sessions and had fewer episodes of oxygen desaturation during
breast-feeding. A characteristic sucking waveform associated with organized
breathing was observed for some infants during bottle-feeding with the
orthodontic nipple. CONCLUSIONS: These data suggest that the orthodontic nipple
is appropriate for supplementing breast-feeding for some preterm infants. Further
research is needed to examine long-term outcomes.
PMID- 10190833
TI - The perimenopausal transition of Filipino American midlife women:
biopsychosociocultural dimensions.
AB - OBJECTIVES: To describe the biologic, psychological, social, and cultural
(biopsychosociocultural) dimensions of the perimenopausal transition of Filipino
American midlife women. METHODS: A community-based sample of 165 women (a) self
identified as Filipino American, (b) ages 35 to 56 years, and (c) English
language proficient was recruited from churches and social groups. RESULTS: Women
in the study were born in the Philippines (93.3%), had lived in the United States
an average of 18.4 +/- 8.7 years, were married or partnered (74.6%), had
completed college (62.8%) or a graduate degree (15.9%), worked (full-time, 77.9%;
part-time, 12.9%), had household incomes greater than $50,000 (>58%). Menopause
ages were calculated from reports of last menstrual periods (natural, 48.9 +/-
4.9 years; surgical, 42.2 +/- 5.7 years). Neither the age at menarche nor the
number of pregnancies and children born was significantly related to age at
menopause. Calcium from food sources was generally low, and the Center for
Epidemiological Studies Depression Scale (CES-D) revealed a 24.8% depression
rate. The low prevalence of physical health problems confirms previous research
that foreign-born individuals have better health than those born in the United
States. CONCLUSIONS: The profile of this understudied group identified calcium
intake, osteoporosis morbidity, and prevalence of depression as key areas for
future study.
PMID- 10190835
TI - The effects of prescribed versus ad libitum feedings and formula caloric density
on premature infant dietary intake and weight gain.
AB - BACKGROUND: Although feedings that are organized on an ad lib basis (i.e., in
response to infant cues of hunger and of satiation) could enhance an infant's
self-regulatory capacities for feeding, ad lib feeding of fully nipple-fed
premature infants in a special care nursery has not been examined. OBJECTIVE: To
study whether the caloric and protein intake and weight change of fully nipple
fed preterm infants differed by the feeding regimen (prescribed or ad lib) and by
the caloric density of the formula (20- or 24-kcalories per ounce). METHOD: The
78 infants who participated in the study were randomized to prescribed or ad lib
feeding regimens and, within each regimen, were further randomized to receive
either 20-calorie or 24-kcalorie per ounce formula. Dietary intake (volume/kg,
caloric intake/kg) and weight change (grams/kg gained or lost) were assessed for
each of the 5 study days. Multivariate data analysis was used to examine the
effects of feeding regimen and caloric density on dietary intake and weight
change, controlling biologic variables (infant gender, race, lung disease
diagnosis, treatment with supplemental oxygen, gestational age and weight at
birth, and weight on the day prior to full nipple-feeding). RESULTS: Overall, the
ad lib feeding regimen had a negative effect on volume intake and caloric intake.
Weight gain was influenced by caloric intake, but not by feeding regimen or the
caloric density of the diet. With increased full nipple-feeding experience,
caloric intake of ad lib feeders approached that of the infants fed on the
prescribed regimen. CONCLUSIONS: Development of self-regulatory capacities
through ad lib feeding experience was indicated by infant regulation of the
volume of intake by the caloric density of the formula, an unexpected finding.
Furthermore, the approach of the caloric intake of infants on the ad lib regimen
to that of infants on the prescribed regimen suggests they had gained skill in
regulating intake with experience. Whether or not the trend for similar intakes
would continue beyond 5 days is a question for further study.
PMID- 10190836
TI - Methodologic principles of cost analyses in the nursing, medical, and health
services literature, 1990-1996.
AB - BACKGROUND: Cost analyses are needed to inform resource decisions. Oftentimes,
however cost-benefit analysis (CBA), cost-effectiveness analysis (CEA), cost
minimization analysis (CMA), and cost-utility analysis (CUA) are performed using
untested techniques and adhering to a variety of questionable principles.
OBJECTIVES: To analyze, compare, and present a set of useful principles for the
main types and methods of cost analyses through a synthesis of current
information in the published literature. METHODS: The area of interest included
all reports of cost research published as full articles in professional journals
from January 1990 to August 1996 in the nursing, medical, and health services
fields. In all, 88 sampled articles met the criteria for inclusion. A four-page
data collection guide with 28 items grouped as demographics, cost-analysis types,
methods, and principles was designed for the review. Incremental testing for
interrater reliability using the kappa statistic for two raters was performed.
Sampling, process-oriented, construct, and correlational validity were assessed.
RESULTS: The 88 articles included 4 from nursing, 59 from medical, and 25 from
health services journals. Of these articles, 45 (51%) reported CBA, 36 (41%) CEA,
2 CMA, 4 CUA, and 1 both CBA and CEA. Three nursing studies were authored only by
nurses. Three fourths of the medical and four fifths of the health services
publications had interdisciplinary authorship. Existing databases were the
primary source of data in 61 (69%) publications. Adherence to six main
methodologic principles was apparent in 19 (22%) articles. None of the nursing
studies adhered to all six principles, whereas 16% of the health services and 25%
of the medical studies did. CONCLUSIONS: Funded cost analyses of nursing
interventions that adhere to the six known methodologic principles are needed to
inform policy-level health care decisions. Because of the complexity of cost
analysis methodology, including sensitivity analysis, future interdisciplinary
efforts using existing databases may prove most effective. The six methodologic
principles presented in this article can be useful for future nursing education
and cost-analysis research designed to control cost and increase the quality of
health care.
PMID- 10190837
TI - The effects of crossed leg on blood pressure measurement.
AB - BACKGROUND: It is clear that numerous factors influence an individual's blood
pressure measurement. However, guidelines for accurately measuring blood pressure
inconsistently specify that the patient should keep feet flat on the floor.
OBJECTIVE: To determine if the crossing of a leg at the knee during blood
pressure measurement has an effect on the patient's blood pressure reading.
METHODS: A convenience sample of 100 hypertensive male subjects was selected from
various outpatient clinics in an inner-city acute-care veterans' hospital. The
first 50 subjects positioned their feet flat on the floor while their blood
pressure was measured. After 3 minutes, the blood pressure was measured again
with the subject's leg crossed at the knee. The procedure was reversed for the
second 50 subjects. RESULTS: The results indicated that both systolic and
diastolic blood pressure increased significantly (p < .0001) with the crossed leg
position. CONCLUSION: When blood pressure is measured, patients should be
instructed to have feet flat on the floor to eliminate a potential source of
error.
PMID- 10190838
TI - Impedance cardiography for noninvasive measurement of cardiovascular
hemodynamics.
PMID- 10190839
TI - Managing the informed consent process in large multicenter projects.
PMID- 10190840
TI - Critical care ethics in Asia: global or local?
PMID- 10190841
TI - Critical care in the Philippines: the "Robin Hood Principle" vs. Kagandahang
loob.
AB - Practical medical decisions are closely integrated with ethical and religious
beliefs in the Philippines. This is shown in a survey of Filipino physicians'
attitudes towards severely compromised neonates. This is also the reason why the
ethical analysis of critical care practices must be situated within the context
of local culture. Kagandahang loob and kusang loob are indigenous Filipino
ethical concepts that provide a framework for the analysis of several critical
care practices. The practice of taking-from-the-rich-to-give-to-the-poor in
public hospitals is not compatible with these concepts. The legislated definition
of death and other aspects of the Philippine Law on Organ Transplants also fail
to be compatible with these concepts. Many ethical issues that arise in a
critical care setting have their roots outside the seemingly isolated clinical
setting. Critical care need not apply only to individuals in a serious clinical
condition. Vulnerable populations require critical attention because potent
threats to their lives exist in the water that they drink and the air that they
breathe. We cannot ignore these threats even as we move inevitably towards a
technologically dependent, highly commercialized approach to health management.
PMID- 10190842
TI - Ethical challenges in critical care medicine: a Chinese perspective.
AB - The major ethical challenges for critical care medicine in China include the high
cost of patient care in the ICU, the effect of payment mechanisms on access to
critical care, the fact that much more money is spent on patients who die than on
ones who live, the extent to which an attempt to rescue and save a patient is
made, and the great geographical disparity in distribution of critical care. The
ethical problems surrounding critical care medicine bear much relation to the
culture, public policy and health care system in China. The essay concludes that
China should allocate more resources to ordinary medical services rather than to
critical care medicine.
PMID- 10190843
TI - Serving the emperor without asking: critical care ethics in Japan.
AB - This article is an attempt by Japanese physicians to introduce the practice
patterns and moral justification of Japanese critical care to the world. Japanese
health care is characterized by the fact that the fee schedule does not reward
high technology medicine, such as surgery and critical care. In spite of the low
reimbursement, our critical care practice pattern is characterized by continuing
futile treatment for terminal patients in the intensive care unit (ICU). This
apparently wasteful practice can be explained by fundamental Japanese cultural
values, social factors in Japan, the availability of extensive insurance
coverage, physicians' psychological factors, lack of cost-benefit considerations
and the pragmatic approach the Japanese take to situations. We attempt to make
some brief suggestions regarding the improvement of our critical care practices.
Although we can not fully present quantitative data to support our argument, this
article represents our real-world approaches to the ethical issues in the ICU in
Japan.
PMID- 10190844
TI - Critical care ethics in Hong Kong: cross-cultural conflicts as east meets west.
AB - The practice of critical care medicine has long been a difficult task for most
critical care physicians in the densely populated city of Hong Kong, where we
face limited resources and a limited number of intensive care beds. Our triage
decisions are largely based on the potential of functional reversibility of the
patients. Provision of graded care beds may help to relieve some of the demands
on the intensive care beds. Decisions to forego futile medical treatment are
frequently physician-guided family-based decisions, which is quite contrary to
the Western focus on patient autonomy. However, as people acquire knowledge about
health care and they become more aware of individual rights, our critical care
doctors will be able to narrow the gaps between the different concepts of medical
ethics among our professionals as well as in our society. An open and caring
attitude from our intensivists will be important in minimizing the cross-cultural
conflict on the complex issue of medical futility.
PMID- 10190845
TI - A transcultural, preventive ethics approach to critical-care medicine: restoring
the critical care physician's power and authority.
AB - This article comments on the treatment of critical-care ethics in four preceding
articles about critical-care medicine and its ethical challenges in mainland
China, Hong Kong, Japan, and the Philippines. These articles show how cultural
values can be in both synchrony and conflict in generating these ethical
challenges and in the constraints that they place on the response of critical
care ethics to them. To prevent ethical conflict in critical care the author
proposes a two-step approach to the ethical justification of critical-care
management: (1) the decision to resuscitate and initiate critical-care
management, which is based on the obligation to prevent imminent mortality
without permanent loss of consciousness; and (2) the decision to continue
critical-care management, which is based on the obligation both to prevent
imminent death without permanent loss of consciousness and to avoid unnecessary,
significant iatrogenic costs to the patient and psychosocial costs to the family
when the reduction of mortality risk is marginal. Physicians and hospitals should
restore the critical-care physician's authority and power -- against prevailing
cultural values, if necessary -- to control when critical-care intervention is
offered, when it is recommended to continue, and when it is recommended to be
discontinued and the patient allowed to die.
PMID- 10190846
TI - Critical care: why there is no global bioethics.
AB - The high technology and the costs involved in critical care disclose the
implausibility of applying the American standard version of bioethics in the
developing world. The American standard version of bioethics was framed during
the rapid secularization of the American culture, the emergence of a new image
for the medical profession, the development of high technology medicine, an ever
greater demand in resources, and a shift of focus from families and communities
to individuals. This all brought with it a particular ideology of health care
which promised Americans (1) the best of care, (2) equal care, and (3)
physician/patient choice, without (4) runaway costs. This essay argues that this
moral project is impossible in practice. This impossibility is especially salient
in developing countries. In addition to the fact that it is financially
impossible to provide all in the developing world with the standard of care
accepted by law, policy, and convention in developed countries, different moral
perspectives with different orderings of values will seem more or less plausible
in different cultures. Indeed, such an approach would be harmful. A concrete
bioethics applicable across the world does not appear possible.
PMID- 10190847
TI - The immediate effect of a Boston brace on lung volumes and pulmonary compliance
in mild adolescent idiopathic scoliosis.
AB - Idiopathic scoliosis (IS) is known to result in lung volume and pulmonary
compliance reduction. Boston brace treatment of IS is an additional factor
causing restrictive respiratory syndrome due to external chest wall compression.
Nevertheless, the immediate effect of Boston bracing on the pulmonary compliance
of scoliotic patients has not been studied systematically. Spirometric and
plethysmographic lung volumes, static lung compliance (C(ST)(L)) and specific
lung compliance (C(ST)(L)/functional residual capacity) of 15 scoliotic
adolescents (14 females and 1 male, of mean age 14.1+/-1.67 years, with mean Cobb
angle 24.1 degrees+/-7.88 degrees) were recorded twice, in a random sequence:
once without the Boston brace (nBB) and once immediately after wearing the brace
(BB). Our findings showed that bracing reduced vital capacity, residual volume,
functional residual capacity (FRC), total lung capacity, and forced expiratory
volume in 1s in a proportional and significant way (P < 0.001). C(ST)(L) was also
significantly reduced (P < 0.001), but C(ST)(L)/FRC remained unaltered. All BB
and nBB indices were highly correlated. We concluded that Boston bracing in IS
patients results in an immediate, predictable, and uniform reduction of lung
volumes and pulmonary compliance. The reduction of C(ST)(L) under bracing
conditions was related to the decrease of lung volume; the C(ST)(L)/FRC remained
unaltered.
PMID- 10190848
TI - Cotrel-Dubousset instrumentation for the treatment of severe scoliosis.
AB - In a multicentric study, 36 cases (40 curves) of severe scoliosis were analysed;
19 were idiopathic and 17 neurological, Cobb angles ranged from 70 degrees to 145
degrees, all had undergone three-rod Cotrel-Dubousset (CD) instrumentation. The
correction on the frontal plane achieved more than 50% of the preoperative angle
(53.9% for idiopathic curves and 55.6% for neurological ones). On the sagittal
plane the pathological shape of the spine was reduced and distinctly ameliorated.
In ten patients, the authors successfully applied a technique, alternative to the
original one, which was based on the use of two or three screws in the lumbar
area, one supplementary pedicle transverse claw on the cranial area and two rods
connected by a domino, instead of a single rod (the longer one applied on the
concave side). The main complications were: one case of infection, three of
vascular compression of the duodenum, one of crank-shaft phenomenon and one
laminar hook displacement. The excellent result achieved in both, idiopathic and
neurological severe and stiff scoliosis shows the efficacy, reliability and
versatility of CD three-rod instrumentation.
PMID- 10190849
TI - Long-term three-dimensional changes of the spine after posterior spinal
instrumentation and fusion in adolescent idiopathic scoliosis.
AB - This is a prospective study comparing the short- and long-term three-dimensional
(3D) changes in shape, length and balance of the spine after spinal
instrumentation and fusion in a group of adolescents with idiopathic scoliosis.
The objective of the study was to evaluate the stability over time of the
postoperative changes of the spine after instrumentation with multi rod, hook and
screw instrumentation systems. Thirty adolescents (average age: 14.5+/-1.6 years)
undergoing surgery by a posterior approach had computerized 3D reconstructions of
the spine done at an average of 3 days preoperatively (stage I), and 2 months
(stage II) and 2,5 years (stage III) after surgery, using a digital multi-planar
radiographic technique. Stages I, II and III were compared using various
geometrical parameters of spinal length, curve severity, and orientation.
Significant improvement of curve magnitude between stages I and II was documented
in the frontal plane for thoracic and lumbar curves, as well as in the
orientation of the plane of maximum deformity, which was significantly shifted
towards the sagittal plane in thoracic curves. However, there was a significant
loss of this correction between stages II and III. Slight changes were noted in
apical vertebral rotation, in thoracic kyphosis and in lumbar lordosis. Spinal
length and height were significantly increased at stage II, but at long-term
follow-up spinal length continued to increase while spinal height remained
similar. These results indicate that although a significant 3D correction can be
obtained after posterior instrumentation and fusion, a significant loss of
correction and an increase in spinal length occur in the years following surgery,
suggesting that a crankshaft phenomenon may be an important factor altering the
long-term 3D correction after posterior instrumentation of the spine for
idiopathic scoliosis.
PMID- 10190850
TI - Complications of scoliosis surgery in children with myelomeningocele.
AB - The purpose of the present study was to evaluate whether the high incidence of
complications in scoliosis surgery in myelomeningocele (MMC) could be attributed
to the surgical technique and whether improvements were possible. Between 1984
and 1996, 77 patients with MMC and scoliosis were treated surgically. The
clinical and radiological follow-up ranged from 1 to 10 years with a mean follow
up of 3.6 years. The mean age at time of surgery was 12 years 8 months. The
average preoperative scoliosis measured 90.20 degrees and was corrected by 47%.
The first four patients were stabilized with Harrington rods after anterior
correction with a Zielke device (group 1). Twenty-five patients were operated
only from posterior, using Cotrel-Dubousset (CD) instrumentation (group 2). In 13
patients an anterior release and discectomy was performed prior to CD posterior
instrumentation (group 3). In 26 patients (group 4) this was combined with an
anterior instrumentation. The 9 patients of group 5 had congenital vertebral
malformations which made a special treatment necessary. Complications could be
divided into hardware problems, such as implant failure, dislocation or
pseudarthrosis, infections, anesthetic, and neurologic complications. Hardware
problems were seen in 29% of all patients. More hardware problems were seen with
the Harrington rod (75%) and after solitary posterior instrumentation (30%). The
occurrence of pseudarthrosis was dependent on the surgical technique, the extent
of posterior spondylodesis, and lumbosacral fusion. Patients with hardware
problems had a mean loss of correction of 49% compared to 13% in the other
patients. Depending on the different surgical techniques a loss of more than 30%
was seen in 12-75% of the cases. Early postoperative shunt failure occurred in
four cases; delayed failure - after more than 1 year - in three cases. One
patient died within 1 day due to an acute hydrocephalus, another died after 2 1/2
years because of chronic shunt insufficiency with herniation. Wound problems were
not dependent on the surgical technique, but on the extent of posterior
spondylodesis and the lumbosacral fusion. Based on this analysis we believe our
current practice of instrumented anterior and posterior fusion is justified.
Further, we are very careful to check shunt function prior to acute correction of
spinal deformity.
PMID- 10190851
TI - In vivo and in vitro CT analysis of the occiput.
AB - Arguments concerning the best procedure for occipito-cervical fusion have rarely
been based upon occipital bone thickness or only based on in vitro studies. To
close this gap and to offer an outlook on preoperative evaluation of the patient,
28 patients were analysed in vivo by means of spiral CT. Ten macerated human
skulls were measured by means of CT and directly. Measurements were taken
according to a matrix of 66 points following a grid with 1 cm spacing based upon
McRae's line. Maximum thickness in the patient group was met 4 cm above the
reference plane in the median slice (11.87 mm; SD 3.41 mm) and 5 cm above it in
the skull group (15.85 mm; SD 1.81 mm). Correlation between CT and direct
measurements was good (91.79%). Intra-individual discrepancies from one side to
the respective point on the other side are common (difference > 1 mm in 60%).
Judging areas suitable for operative fixation using the 10% percentile value
(6.68 mm for the maximum value of 11.87 mm) led to the conclusion that screws
should only be inserted along the occipital crest in an area extending from 1.5
cm above the posterior margin of the foramen magnum to the external occipital
protuberance (EOP). At the level of the EOP screws may also be inserted up to 1
cm lateral of the midline. A reduction of screw length to 7 mm (9 mm for the EOP)
is proposed. Preoperative evaluation of the patient should be carried out by
spiral CT with 1 mm slicing and sagittal reconstructions.
PMID- 10190852
TI - Extradural inflammation associated with annular tears: demonstration with
gadolinium-enhanced lumbar spine MRI.
AB - Annular tears are manifest on MRI as the high-intensity zone (HIZ) or as annular
enhancement. Patients with annular tears may experience low back pain with
radiation into the lower limb in the absence of nerve root compression.
Inflammation of nerve roots from leak of degenerative nuclear material through
full-thickness annular tears is a proposed mechanism for such leg pain. The aim
of this study is to illustrate the appearance of extradural enhancement adjacent
to annular tears in patients being investigated for low back pain with radiation
into the lower limb(s). Sagittal T1- and T2-weighted spin echo and axial T1
weighted spin echo sequences were obtained in eight patients being investigated
for low back and leg pain. In all patients, the T1-weighted sequences were
repeated following intravenous gadopentetate dimeglumine (Gd-DTPA). Annular tears
were identified at 12 sites in eight patients. Extradural inflammation appeared
as a region of intermediate signal intensity replacing the fat between the
posterior disc margin and the theca, which enhanced following Gd-DTPA. The
inflammatory change was always associated with an annular tear, and in four cases
directly involved the nerve root. Enhancement of the nerve root was seen in two
cases. The findings may be relevant in the diagnosis of chemical radiculopathy
secondary to inflammation at the site of an annular leak from a degenerating
disc.
PMID- 10190853
TI - Acute systematic and variable postural adaptations induced by an orthopaedic shoe
lift in control subjects.
AB - A small leg length inequality, either true or functional, can be implicated in
the pathogenesis of numerous spinal disorders. The correction of a leg length
inequality with the goal of treating a spinal pathology is often achieved with
the use of a shoe lift. Little research has focused on the impact of this
correction on the three-dimensional (3D) postural organisation. The goal of this
study is to quantify in control subjects the 3D postural changes to the pelvis,
trunk, scapular belt and head, induced by a shoe lift. The postural geometry of
20 female subjects (X = 22, sigma = 1.2) was evaluated using a motion analysis
system for three randomised conditions: control, and right and left shoe lift.
Acute postural adaptations were noted for all subjects, principally manifested
through the tilt of the pelvis, asymmetric version of the left and right iliac
bones, and a lateral shift of the pelvis and scapular belt. The difference in the
version of the right and left iliac bones was positively associated with the
pelvic tilt. Postural adaptations were noted to vary between subjects for
rotation and postero-anterior shift of the pelvis and scapular belt. No notable
differences between conditions were noted in the estimation of kyphosis and
lordosis. The observed systematic and variable postural adaptations noted in the
presence of a shoe lift reflects the unique constraints of the musculoskeletal
system. This suggests that the global impact of a shoe lift on a patient's
posture should also be considered during treatment. This study provides a basis
for comparison of future research involving pathological populations.
PMID- 10190854
TI - A clinico-pathological study of cervical myelopathy in rheumatoid arthritis: post
mortem analysis of two cases.
AB - Two patients who developed cervical myelopathy secondary to rheumatoid arthritis
were analyzed post mortem. One patient had anterior atlanto-axial subluxation
(AAS) combined with subaxial subluxation (SS), and the other had vertical
subluxation (VS) combined with SS. In the patient with AAS, the posterior aspect
of the spinal cord demonstrated severe constriction at the C2 segment, which
arose from dynamic osseous compression by the C1 posterior arch. A histological
cross-section of the spinal cord at the segment was characterized by distinct
necrosis in the posterior white columns and the gray matter. In the patient with
VS, the upper cervical cord and medulla oblongata showed angulation over the
invaginated odontoid process, whereas no significant pathological changes were
observed. At the level of SS, the spinal cord was pinched and compressed between
the upper corner of the vertebral body and the lower edge of the lamina.
Histologically, demyelination and gliosis were observed in the posterior and
lateral white columns.
PMID- 10190855
TI - Can autologous bone culture predict spinal fusion capacity?
AB - The capacity of the individual patient to initiate osteoblast proliferation as a
predictor for successful lumbar spinal fusion has not yet been reported. The
objectives of this study were, first, to analyze the relationship between in
vitro osteoblast proliferation and clinical bony fusion in the individual patient
in order to predict the fusion outcome and, second, to measure the effect of
preoperative tobacco smoking on osteoblast proliferation. Sixty-one patients
(mean age 46 years) underwent posterolateral lumbar fusion in the period 1994
1995. Thirty-eight patients received CD pedicle screw implants and 23 received
posterolateral fusions alone. During surgery, autogenous iliac bone was harvested
and 1 g of trabecular bone without blood or bone marrow was then isolated for
cell culturing. The cultures were classified as excellent (confluence within 4
weeks), good (confluence between 4 and 6 weeks) and poor (no or poor growth).
Spine fusion was evaluated by two independent observers from plain anterior
posterior, lateral, and flexion/extension radiographs taken 1 year
postoperatively, and the functional outcome was measured by the Dallas Pain
Questionnaire (DPQ). Twenty-three patients had excellent, 19 good, and 19 poor in
vitro osteoblast proliferation. Bony fusion was obtained in 77% of patients: 83%
in the CD instrumentation group and 70% in the non-instrumentation group (NS).
There was no significant correlation between osteoblast proliferation and spinal
fusion or functional outcomes when analyzing the CD instrumentation and non
instrumentation groups together or separately. Elderly patients had a
significantly poorer osteoblast proliferation than younger patients (P < 0.008).
Preoperative tobacco consumption had no discernible effect on osteoblast
proliferation, and no correlation between smoking and fusion was found. Further
refinement of autologous osteoblast culturing may provide a biological tool for
selection of patients who require biological enhancement of their bone fusion
capacity. The poorer osteoblast proliferation related to advanced age supports
the important negative biological influence of age on bony fusion. However, with
more sensitive testing and better discrimination, other results are possible - or
can in any event not be excluded.
PMID- 10190856
TI - Characteristics of an extended internal fixation system for polysegmental
transpedicular reduction and stabilization of the thoracic, lumbar, and
lumbosacral spine.
AB - The Kluger internal fixator, with its artificial fulcrum outside the operative
site, had to be extended for multisegmental use. Three different prototypes,
called Central Bar (CB), Double Bar I (DB I) and Double Bar II (DB II) were
designed, which were fully compatible with the existing reduction system. To
evaluate the ability of these newly developed systems to provide primary
stability in a destabilized spine, their stiffness characteristics and
stabilizing effects were investigated in multidirectional biomechanical stability
tests and compared with those of the clinically well-known Cotrel-Dubousset (CD)
system. The investigations were performed on a spine tester using freshly
prepared calf spines. The model tested was that of an intact straight spine
followed by a defined three-column lesion simulating the most destabilizing type
of injury. Pure moments of up to 7.5 Nm were continuously applied to the top of
each specimen in flexion/extension, left/right axial rotation, and left/right
lateral bending. Segmental motion was measured using a three-dimensional
goniometric linkage system. Range of motion and stiffness within the neutral zone
were calculated from obtained load-displacement curves. The DB II attained 112.5%
(P = 0.26) of the absolute stiffness of the CD system in flexion and enhanced its
stability in extension by up to 144.3% (P = 0.004). In axial rotation of the
completely destabilized spine, this system achieved 183.3% of the stiffness of
the CD system (P < 0.001), and in lateral bending no motion was measured in the
most injured specimens stabilized by the DB II. The DB I, which was the first to
be designed and was considered to provide high biomechanical stability, did not
attain the stiffness standard set by the CD system in either flexion/extension or
axial rotation of the most injured spine. The study confirms that it is
worthwhile to evaluate in vitro the biomechanical properties of a newly developed
implant before its use in patients, in order to refine weak construction points
and help to reduce device-related complications and to better evaluate its
efficacy in stabilizing the spine.
PMID- 10190857
TI - Ten- to 15-year outcome of surgery for lumbar disc herniation: radiographic
instability and clinical findings.
AB - The most appropriate treatment for radiculopathy associated with disc pathology
is still controversial. Since 1934, surgical treatment has consisted of
hemilaminectomy and removal of the herniated material. Many authors believe that
these procedures may cause degenerative spondylosis and vertebral instability.
Several surgical methods have been proposed, but the long-term effects are still
being debated. In addition there appear to be few well-designed outcome studies
on the management of this disease. In the present study, 150 patients were
selected for surgery with strict criteria and all treated with the standard
technique. The series was evaluated by subjective analyses (Roland questionnaire;
120 patients), objective examinations (68 patients - 56.6%) and radiographic
studies including dynamic views (analyzed by the Taillard and Boxall methods) to
establish the presence of vertebral instability (50 patients - 41.6%). The
subjective and objective analyses showed a high rate of good results.
Radiographic studies showed vertebral instability in 30 cases, but only 9 were
symptomatic. Recurrences were not observed and only a few patients suffered from
leg pain. The standard procedure for lumbar disc herniation showed good results
at 10- and 15-year follow-up.
PMID- 10190858
TI - Spondyloptosis and multiple-level spondylolysis.
AB - An unusual case of a combination of multiple bilateral spondylolyses (L2, 3 and
4), spondylolisthesis at L3/4, spondyloptosis at L4/5 and sacralization of L5 in
a teenage female is described. The patient had severely increasing lower back
pain radiating to the left lower limb. Radiography identified the abnormalities
and myelography revealed complete obstruction and compression of the thecal sac
at the L4/5 level. The case was treated surgically by posterior decompression,
corpectomy and fusion in a three-stage operation. The follow-up was extended to 2
years with no complications. No similar case has previously been reported.
PMID- 10190859
TI - Hypoglossal nerve injury as a complication of anterior surgery to the upper
cervical spine.
AB - Injury to the hypoglossal nerve is a recognised complication after soft tissue
surgery in the upper part of the anterior aspect of the neck, e.g. branchial cyst
or carotid body tumour excision. However, this complication has been rarely
reported following surgery of the upper cervical spine. We report the case of a
35-year-old woman with tuberculosis of C2-3. She underwent corpectomy and fusion
from C2 to C5 using iliac crest bone graft, through a left anterior oblique
incision. She developed hypoglossal nerve palsy in the immediate postoperative
period, with dysphagia and dysarthria. It was thought to be due to traction
neurapraxia with possible spontaneous recovery. At 18 months' follow-up, she had
a solid fusion and tuberculosis was controlled. The hypoglossal palsy persisted,
although with minimal functional disability. The only other reported case of
hypoglossal lesion after anterior cervical spine surgery in the literature also
failed to recover. It is concluded that hypoglossal nerve palsy following
anterior cervical spine surgery is unlikely to recover spontaneously and it
should be carefully identified.
PMID- 10190860
TI - Epidural/perineural injection.
PMID- 10190861
TI - Immune response against Leishmania antigens in dogs naturally and experimentally
infected with Leishmania infantum.
AB - Cell-mediated and humoral immune response in naturally and experimentally
infected dogs was studied using crude and pure antigens. Both types of infections
induced severe signs of visceral disease, but the symptoms observed in natural
infections were more pronounced than in experimental infections. In addition,
asymptomatic infections were not observed in experimentally infected animals.
Disease evolution in laboratory infections was rapid and an increase in antibody
titer to crude parasite antigen was correlated with the appearance and
aggravation of clinical symptoms. Peripheral blood lymphocyte proliferation to
crude antigen and pure gp63 was observed early following experimental infection,
but was abolished once the infected dogs began to exhibit clinical signs. A
similar pattern was observed in naturally infected dogs. Serum from all patent
dogs showed high antibody titers to rK39 in enzyme-linked immunosorbent assays
(ELISA), and reacted by western blotting with several antigens, 12 to 120 KDa,
including gp63 and gp70. In the case of asymptomatic dogs. antibody titers to
crude antigen were low and only a few antigens were identified by western
blotting. None of the pure proteins examined, gp63, gp70, and rK39 were
recognized by western blotting or ELISA. However, asymptomatic dogs exhibited
specific lymphocyte proliferation to both crude antigen and the potential vaccine
candidate gp63.
PMID- 10190862
TI - Oocysts, IgG levels and immunoblot patterns determined for Cryptosporidium parvum
in bovine examined during a visit to a farm (northeastern Spain).
AB - Single fecal and serum samples were individually collected from 101 bovines
selected at random during a visit to a farm in northeastern Spain (Group I, 26
animals aged 2-36 days; Group II, 34 animals aged 1.5-4.5 months; Group III, 41
animals aged 20-24 months). Testing for the presence of Cryptosporidium parvum
oocysts in feces (Monofluo Kit Cryptosporidium, Diagnostics Pasteur, France)
indicated that 26% animals were infected (81% of Group I, 15% of Group II and 0%
of Group III). Serological testing (ELISA for detection of specific anti-C.
parvum IgG) indicated that 59% animals were seropositive (12% of Group I, 74% of
Group II and 78% of Group III). Immunoblotting results indicate that cattle sera
recognize C. parvum antigens of widely varying molecular weights and that the
number of antigens recognized increases with age. Immunoblots revealed that some
of the sera belonging to the Group I reacted with protein fractions between 15
and 20 kDa but none recognized the 21-23 kDa antigen. Only few sera in the Group
II recognized the protein fraction between 15 and 20 kDa. The recognition of 21
23 kDa fraction was observed by four sera from uninfected and seropositive
animals. Sera from all the seronegative Group II animals recognized few antigens
and always with molecular weight greater than 50 kDa. Serum samples from both
seropositive and seronegative animals belonging to the Group III recognized
antigens with molecular weight ranging 15-20 kDa. Surprisingly, the protein
fractions between 21 and 28 kDa reacted with approximately 30% of the sera from
seropositive animals and only one of the nine sera from seronegative animals. The
recognition of 42-46 kDa antigens increased with the age and only reacted with
the sera from uninfected animals.
PMID- 10190863
TI - Isoenzyme activities of different strains of Cryptosporidium parvum.
AB - Different isoenzyme activities have been assayed in three strains of
Cryptosporidium parvum, C1 (C. parvum from infected calves, UK), C2 (C. parvum
from infected calves, Egypt) and C3 (C. parvum from infected goats, Egypt). The
electrophoretic variations of five enzymes; lactate dehydrogenase (LDH), glucose
phosphate isomerase (GPI), hexokinase (HK), malate dehydrogenase (MDH) and
glutamate dehydrogenase (GLDH) were compared among the three different isolates
using native polyacrylamide gel-electrophoresis. LDH showed an identical pattern
in the three isolates. GPI showed two different bands in C3 and C1, with both
bands present in C2. HK activity showed a weak band in C1 but no reaction was
detected with C2 and C3. Malate dehydrogenase (MDH) showed no reaction in C1, but
similar bands in C2 and C3. Glutamate dehydrogenase (GLDH) showed two different
patterns, C2 and C3 had one pattern and C1 showed additional zones of reaction.
Rat liver homogenate was run at the same time as the parasite extracts as a
positive control. This investigation suggests that GPI, HK and GLDH could be used
to characterise different Cryptosporidium isolates.
PMID- 10190864
TI - Differentiation of porcine Eimeria spp. by morphologic algorithms.
AB - Oocysts of Eimeria spp. were isolated from feces of naturally infected sows by
conventional flotation. Saturated sodium chloride solution was superior to zinc
chloride, zinc chloride/sodium chloride or sugar solution to isolate oocysts.
Seven species, namely Eimeria scabra, E. polita, E. perminuta, E. debliecki, E.
suis, E. porci and E. spinosa, were identified. The dimensions of oocysts (n =
4088) and sporocysts (n = 3594) were measured with an image analysis system;
colour and shape of oocysts were estimated and transformed to numerical values.
Of the 4088 oocysts approximately 99% were allocated to the correct species by
algorithms calculated on the basis of these values. Rough-walled oocysts (E.
scabra, E. polita, E. perminuta, E. spinosa) could be distinguished without
previous sporulation in most cases (>97%). Smooth-walled oocysts require
sporulation for further classification and were accurately allocated to species
in at least 93% of cases.
PMID- 10190865
TI - Comparison of arithmetic and geometric means as measures of a central tendency in
cattle nematode populations.
AB - Efficacy calculations in anthelmintic studies require estimates of the central
tendency for the nematode populations. Confusion exists among practitioners
regarding which measures of central tendency are most appropriate; although the
arithmetic mean is frequently used, there are theoretical reasons for preferring
the geometric mean. To investigate this controversy, arithmetic and geometric
means were compared for their suitability for use in measuring efficacy.
Arithmetic and geometric means were compared as measures of central tendency for
skewed distributions. The following criteria were developed to facilitate the
comparison: (1) probability around the parameter, (2) influence of extreme
values, and (3) proximity to the median. Under log-normality, theoretical results
demonstrated the superiority of the geometric mean. Modified-bootstrap
simulations using empirical data from cattle were used to confirm theoretical
expectations. Simulations on log-normal data supported the geometric mean as the
better indicator of the central tendency. Additionally, for data not confirmed as
log-normal, the superiority of geometric means was demonstrated. In a comparison
of precision, it was shown that mean squared error was always smaller for sample
geometric means than for arithmetic means when n> or =2. Simulation results added
support to that conclusion.
PMID- 10190866
TI - A sensitive polymerase chain reaction based assay for the detection of Setaria
digitata: the causative organism of cerebrospinal nematodiasis in goats, sheep
and horses.
AB - A sensitive PCR assay for the detection of Setaria digitata has been developed.
Two oligonucleotide primers (17 nt) were designed from a previously cloned and
characterized tandemly arranged repetitive sequence of Setaria digitata. Using
these primers, it was possible to amplify small quantities (100 fg) of S.
digitata genomic DNA. A simple procedure, using proteinase K and non-ionic
detergent NP 40, was followed to process the host blood samples and mosquitoes
harbouring L3 larvae. The sensitivity of the polymerase chain reaction based
assay surpasses the microscopic detection and the previously reported
oligonucleotide based chemiluminescent detection of microfilariae in infected
host blood samples and L3 larvae in mosquitoes.
PMID- 10190867
TI - Tsetse challenge, trypanosome and helminth infection in relation to productivity
of village Ndama cattle in Senegal.
AB - Data on tsetse fly, and on village Ndama cattle collected over a 4-year period in
southern Senegal, were analysed. A total of 431 Ndama cattle in four herds of
three villages in the Upper Casamance area of southern Senegal were monitored
monthly. Glossina morsitans submorsitans and Glossina palpalis gambiensis are
present in the study area. Mean tsetse apparent density was 5.4 flies/trap/day.
Trypanosome (Trypanosoma congonlense and Trypanosoma vivax) infection rate in
flies was 2.4 (s.e. 0.37)%. Tsetse challenge index was 17.3 (s.e. 4.18). Mean
monthly trypanosome prevalence in cattle was 2.5 (s.e. 0.51)%. Highest
trypanosome prevalence occurred during the dry season, and animals less than 1
year old were more frequently infected than older animals. The linear
relationship between the log10+1 tsetse challenge and the arcsine of the
trypanosome prevalence was significant only when mean monthly values of these
variables over the 4-year period were used with tsetse challenge preceding
infection rate by 3 months. Mean monthly prevalence of strongyle, Strongyloides
spp., Toxocara spp. and coccidia were 34.4 (s.e. 0.60), 2.1 (s.e. 0.18), 1.2
(s.e. 0.45) and 15.6 (s.e. 0.47)%, respectively. Calf mortality rate at 1,6 and
12 months of age was 2.1 (s.e. 2.1), 5.2 (s.e. 2.8) and 12.2 (s.e. 3.3)%,
respectively. Calving interval (584 s.e. 58 days) was not influenced by
trypanosome status of the cow during lactation. Calving interval was shorter by
167 days when the calf died before 1 year of age in comparison to calving
intervals for which the calf survived beyond one year. Live weight at birth, 6
and 12 months of age were 15.8 (s.e. 0.54), 48.1 (s.e. 2.56) and 71.1 (s.e. 5.44)
kg, respectively. Mean lactation length, total and daily milk offtake were 389
(s.e. 16) days, 231 (s.e. 15) litres and 0.69 (s.e. 0.037) litres, respectively.
Trypanosome infection during lactation did not have a significant effect on the
amount of milk extracted for human consumption nor did trypanosome status affect
calf growth.
PMID- 10190868
TI - The efficacy of simplified eradication strategies against sarcoptic mange mite
infections in swine herds monitored by an ELISA.
AB - Eradication programmes directed against Sarcoptes scabiei var. suis, performed
without any disinfection of the environment, were compared to an eradication
programme including a simultaneous environmental disinfection. The performance of
such programmes would be facilitated considerably if environmental disinfection
could be avoided. The trial was conducted in four conventional piglet-producing
herds designated A-D. All herds suffered from a subclinical but persistent
infection with the sarcoptic mite. Herd A was treated with two injections of
ivermectin and simultaneously disinfection of the environment was done. In the
other herds, the animals were treated twice (B and C) or three times (D) with
acaricides (ivermectin or phoxim) at intervals of 7-12 days without any
simultaneous disinfection of the buildings or environment. The results were
monitored by attempts to demonstrate the mite by skin scrapings, and by
monitoring the levels of serum antibodies to Sarcoptes scabiei by an ELISA.
Samples were taken from all adults and from 20% of the piglets aged 10-12 weeks,
before initiating the control programmes, every third month during the first year
and a final sampling 18 months after the treatments. After treatment, the levels
of antibodies continuously decreased. Presumably dead S. scabiei were
demonstrated in one sow from two of the herds 3 months after initiating
acaricidal treatments. S. scabiei was not demonstrated later, nor from skin
scrapings of the piglets. The results obtained demonstrate that it is possible to
eradicate sarcoptic mange mites in swine herds with the use of simplified
eradication programmes. The success of such programmes may efficiently be
monitored by measuring the levels of serum antibodies to S. scabiei.
PMID- 10190870
TI - Patient protection: health reform on the line.
PMID- 10190869
TI - Antibody response in goats experimentally infected with Toxoplasma gondii.
AB - Serum samples of five goats inoculated with Toxoplasma gondii were analyzed using
the enzyme linked immunosorbent assay (ELISA), indirect hemagglutination (IHA)
and western blotting (WB). Antibodies detected by ELISA peaked between 19 and 62
days after inoculation and persisted throughout the experiment with no
association to parasitaemia. Using WB, the main antigens detected had molecular
weights of approximately 68, 62, 50, 48, 42, 34, 28, 26, 22 and 19 kDa. Antibody
titers of between 1:256 and 1:32000 were observed using IHA, with a significant
drop in activity after treatment with 2-mercapto-ethanol between days 12 and 48.
This coincided with the parasitaemic period that occurs between 5 and 64 days
after inoculation.
PMID- 10190871
TI - Cancer and atherosclerosis: the broad mandate of angiogenesis.
PMID- 10190872
TI - Effects of human cytomegalovirus immediate-early proteins on p53-mediated
apoptosis in coronary artery smooth muscle cells.
AB - BACKGROUND: Restenotic and atherosclerotic lesions often contain smooth muscle
cells (SMCs), which display high rates of proliferation and apoptosis. Human
cytomegalovirus (HCMV) may increase the incidence of restenosis and predispose to
atherosclerosis. Although the mechanisms contributing to these processes are
unclear, studies demonstrate that one of the immediate-early (IE) gene products
of HCMV, IE2-84, binds to and inhibits p53 transcriptional activity. Given the
role of p53 in mediating apoptosis, we studied the ability of IE2-84 to inhibit
p53-dependent apoptosis in human coronary artery SMCs. METHODS AND RESULTS:
Apoptosis of SMCs was induced either by use of an adenovirus vector encoding
human wild-type p53 protein or by treatment with doxorubicin. HCMV IE1-72 and IE2
84, the major IE proteins of HCMV, were overexpressed separately with adenovirus
vectors encoding each protein, and the effects on p53-induced apoptosis were
examined by both nick end-labeling (TUNEL) assay and flow cytometry. Expression
of IE2-84, but not IE1-72, protected SMCs from p53-mediated apoptosis.
CONCLUSIONS: These data indicate that an HCMV IE protein antagonizes p53-mediated
apoptosis, suggesting a pathway by which HCMV infection predisposes to SMC
accumulation and thereby contributes to restenosis and atherosclerosis.
PMID- 10190873
TI - Effects of intracoronary beta-radiation therapy after coronary angioplasty: an
intravascular ultrasound study.
AB - BACKGROUND: Endovascular radiation is emerging as a potential solution for the
prevention and treatment of restenosis. Its effects on the morphology of
unstented vessels cannot be determined by angiography and therefore require the
use of intravascular ultrasound. METHODS AND RESULTS: Through a 5F noncentered
catheter for delivery of a 90Sr/Y source train, 12, 14, or 16 Gy at 2 mm was
delivered to native coronary arteries after successful balloon angioplasty in 30
patients. Four patients required stent deployment in the first week. Quantitative
coronary angiography and IVUS were performed during the initial procedure and at
6-month follow-up. Binary angiographic restenosis was present in 3 of 30
patients, with target lesion and vessel revascularization performed in 3 and 5
patients, respectively. Angiographic late loss was -0.02+/-0.60 mm, with a
0.09+/-0.46 loss index. IVUS demonstrated no significant reduction in lumen area
(from 5.69+/-1.72 mm2 after treatment to 6. 04+/-2.63 mm2 at follow-up), with no
significant change in external elastic membrane area (13.71+/-4.54 to 14.22+/
4.71 mm2) over the 6-month follow-up. Wall area was 8.01+/-3.85 mm2 after
radiation therapy and 8.19+/-3.44 mm2 at follow-up (P=NS). No significant
differences were noted between the different dose groups. CONCLUSIONS: beta
Radiation therapy resulted in a low restenosis rate with negligible late loss by
angiography. By IVUS, beta-radiation was shown to inhibit neointima formation,
with no reduction of total vessel area at 6-month follow-up.
PMID- 10190874
TI - Acute anti-ischemic effect of testosterone in men with coronary artery disease.
AB - BACKGROUND: The role of testosterone on the development of coronary artery
disease in men is controversial. The evidence that men have a greater incidence
of coronary artery disease than women of a similar age suggests a possible causal
role of testosterone. Conversely, recent studies have shown that the hormone
improves endothelium-dependent relaxation of coronary arteries in men.
Accordingly, the aim of the present study was to evaluate the effect of acute
administration of testosterone on exercise-induced myocardial ischemia in men.
METHODS AND RESULTS: After withdrawal of antianginal therapy, 14 men (mean age,
58+/-4 years) with coronary artery disease underwent 3 exercise tests according
to the modified Bruce protocol on 3 different days (baseline and either
testosterone or placebo given in a random order). The exercise tests were
performed 30 minutes after administration of testosterone (2.5 mg IV in 5
minutes) or placebo. All patients showed at least 1-mm ST-segment depression
during the baseline exercise test and after placebo, whereas only 10 patients had
a positive exercise test after testosterone. Chest pain during exercise was
reported by 12 patients during baseline and placebo exercise tests and by 8
patients after testosterone. Compared with placebo, testosterone increased time
to 1-mm ST-segment depression (579+/-204 versus 471+/-210 seconds; P<0. 01) and
total exercise time (631+/-180 versus 541+/-204 seconds; P<0. 01). Testosterone
significantly increased heart rate at the onset of 1-mm ST-segment depression
(135+/-12 versus 123+/-14 bpm; P<0.01) and at peak exercise (140+/-12 versus
132+/-12 bpm; P<0.01) and the rate-pressure product at the onset of 1-mm ST
segment depression (24 213+/-3750 versus 21 619+/-3542 mm Hgxbpm; P<0.05) and at
peak exercise (26 746+/-3109 versus 22 527+/-5443 mm Hgxbpm; P<0.05).
CONCLUSIONS: Short-term administration of testosterone induces a beneficial
effect on exercise-induced myocardial ischemia in men with coronary artery
disease. This effect may be related to a direct coronary-relaxing effect.
PMID- 10190875
TI - Diagnostic marker cooperative study for the diagnosis of myocardial infarction.
AB - BACKGROUND: Millions of patients present annually with chest pain, but only 10%
to 15% have myocardial infarction. Lack of diagnostic sensitivity and specificity
of clinical and conventional markers prevents or delays treatment and leads to
unnecessary costly admissions. Comparative data are lacking on the new markers,
yet using all of them is inappropriate and expensive. METHODS AND RESULTS: The
Diagnostic Marker Cooperative Study was a prospective, multicenter, double-blind
study with consecutive enrollment of patients with chest pain presenting to the
emergency department. Diagnostic sensitivity and specificity and frequency of
increase in patients with unstable angina were determined for creatine kinase-MB
(CK-MB) subforms, myoglobin, total CK-MB (activity and mass), and troponin T and
I on the basis of frequent serial sampling for =24 hours. Of 955 patients with
chest pain, 119 (12.5%) had infarction identified by use of CK-MB mass, and 203
(21%) had unstable angina. CK-MB subforms were most sensitive and specific (91%
and 89%) within 6 hours of onset, followed by myoglobin (78% and 89%). For late
diagnosis, total CK-MB activity (derived from subforms) was the most sensitive
and specific (96% and 98%) at 10 hours from onset, followed by troponin I (96%
and 93%), but not until 18 hours, and troponin T (87% and 93% at 10 hours). In
unstable angina, CK-MB subforms were increased in 29.5%, myoglobin in 23.7%,
troponin I in 19.7%, and troponin T in 14.8%. All markers were increased in 99
patients. With each marker as the diagnostic standard, CK-MB subforms and
myoglobin remained the most sensitive for early diagnosis. CONCLUSIONS: The CK-MB
subform assay alone or in combination with a troponin reliably triages patients
with chest pain and should lead to improved therapy and reduced cost.
PMID- 10190876
TI - Coronary flow reserve in young men with familial combined hyperlipidemia.
AB - BACKGROUND: Familial combined hyperlipidemia (FCHL) is a common hereditary
disorder of lipoprotein metabolism estimated to cause 10% to 20% of premature
coronary heart disease. We investigated whether functional abnormalities exist in
coronary reactivity in asymptomatic patients with FCHL. METHODS AND RESULTS: We
studied 21 male FCHL patients (age, 34.8+/-5.4 years) and a matched group of 21
healthy control subjects. Myocardial blood flow (MBF) was measured at baseline
and during dipyridamole-induced hyperemia with PET and 15O-labeled water. The
baseline MBF was similar in patients and control subjects (0.79+/-0.19 versus
0.88+/-0.20 mL. g-1. min-1, P=NS). An increase in MBF was seen in both groups
after dipyridamole infusion, but MBF at maximal vasodilation was lower in FCHL
patients (3.54+/-1.59 versus 4.54+/-1.17 mL. g-1. min-1, P=0.025). The difference
in coronary flow reserve (CFR) was not statistically significant (4.7+/-2.2
versus 5.3+/-1.6, P=NS, patients versus control subjects). Considerable
variability in CFR values was detected within the FCHL group. Patients with
phenotype IIB (n=8) had lower flow during hyperemia (2.5+/-1.2 versus 4.2+/-1.5
mL. g-1. min-1, P<0.05) and lower CFR (3.4+/-2.1 versus 5.4+/-2.0, P<0.05)
compared with phenotype IIA (n=13). CONCLUSIONS: Abnormalities in coronary flow
regulation exist in young asymptomatic FCHL patients expressing phenotype IIB
(characterized by abnormalities in both serum cholesterol and triglyceride
concentrations). This is in line with previous observations suggesting that the
metabolic abnormalities related to the pathophysiology of FCHL are associated
with the phenotype IIB.
PMID- 10190877
TI - Inhibition of p38 mitogen-activated protein kinase decreases cardiomyocyte
apoptosis and improves cardiac function after myocardial ischemia and
reperfusion.
AB - BACKGROUND: Activation of p38 mitogen-activated protein kinase (MAPK) plays an
important role in apoptotic cell death. The role of p38 MAPK in myocardial injury
caused by ischemia/reperfusion, an extreme stress to the heart, is unknown.
METHODS AND RESULTS: Studies were performed with isolated, Langendorff-perfused
rabbit hearts. Ischemia alone caused a moderate but transient increase in p38
MAPK activity (3.5-fold increase, P<0.05 versus basal). Ischemia followed by
reperfusion further activated p38 MAPK, and the maximal level of activation (6.3
fold, P<0.01) was reached 10 minutes after reperfusion. Administration of SB
203580, a p38 MAPK inhibitor, decreased myocardial apoptosis (14.7+/-3.2% versus
30.6+/-3.5% in vehicle, P<0.01) and improved postischemic cardiac function. The
cardioprotective effects of SB 203580 were closely related to its inhibition of
p38 MAPK. Administering SB 203580 before ischemia and during reperfusion
completely inhibited p38 MAPK activation and exerted the most cardioprotective
effects. In contrast, administering SB 203580 10 minutes after reperfusion (a
time point when maximal MAPK activation had already been achieved) failed to
convey significant cardioprotection. Moreover, inhibition of p38 MAPK attenuated
myocardial necrosis after a prolonged reperfusion. CONCLUSIONS: These results
demonstrate that p38 MAPK plays a pivotal role in the signal transduction pathway
mediating postischemic myocardial apoptosis and that inhibiting p38 MAPK may
attenuate reperfusion injury.
PMID- 10190878
TI - Design and results of the antiarrhythmics vs implantable defibrillators (AVID)
registry. The AVID Investigators.
AB - BACKGROUND: The Antiarrhythmics Versus Implantable Defibrillators (AVID) Study
compared treatment with implantable cardioverter-defibrillators versus
antiarrhythmic drugs in patients with life-threatening ventricular arrhythmias
(VAs). AVID maintained a Registry on all patients, randomized or not, with any VA
or unexplained syncope who could be considered for either of the treatment
strategies. Trial-eligible arrhythmias were the categories of VF cardiac arrest,
Syncopal VT, and Symptomatic VT, below. METHODS AND RESULTS: Of 5989 patients
screened, 4595 were registered and 1016 were randomized. Mortality follow-up
through 1996 was obtained on the 4219 Registry patients enrolled before 1997
through the National Death Index. Crude mortality rates (mean+/-SD, follow-up,
16.9+/-11.5 months) were: VF cardiac arrest, 17.0% (n=1399, 238 deaths); Syncopal
VT, 21.2% (n=598, 127 deaths); Symptomatic VT, 15.8% (n=1065, 168 deaths); Stable
(asymptomatic) VT, 19.7% (n=497, 98 deaths); VT/VF with transient/correctable
cause, 17.8% (n=270, 48 deaths); and Unexplained syncope, 12.3% (n=390, 48
deaths). CONCLUSIONS: Patients with seemingly lower-risk or unknown-risk VAs
(asymptomatic VT, and VT/VF associated with a transient factor) have a (high)
mortality similar to that of higher-risk, AVID-eligible VAs. The similar (and
poor) prognosis of most patients with VT/VF suggests the need for reevaluation of
a priori risk grouping and raises the question of the appropriate arrhythmia
therapy for a broad range of patients.
PMID- 10190879
TI - Right atrial flutter due to lower loop reentry: mechanism and anatomic
substrates.
AB - BACKGROUND: The mechanisms of an atrial flutter (AFL) that is more rapid and at
times more irregular than typical AFL are unknown. METHODS AND RESULTS: Twenty
nine patients with AFL were studied. Atrial electrograms were recorded from a 20
pole catheter placed against the tricuspid annulus (TA), with its distal
electrodes lateral to the isthmus between the TA and the eustachian ridge (ER),
and from the His bundle and coronary sinus catheters. Atrial extrastimuli were
delivered in the TA-ER isthmus during typical AFL. Episodes of a right atrial
flutter rhythm that was different from typical AFL were induced in 3 patients and
occurred spontaneously in 3 patients. This sustained AFL, designated as lower
loop reentry (LLR), involved the lower right atrium (RA), as manifested by early
breakthrough in the lower RA, wave-front collision in the high lateral RA or
septum, and conduction through the TA-ER isthmus. Linear ablation resulting in
bidirectional conduction block in the TA-ER isthmus terminated spontaneous LLR in
3 patients and rendered LLR noninducible in all patients. The cycle length of LLR
was shorter than that of typical AFL (217+/-32 versus 272+/-40 ms, P<0. 01).
Alternating LLR and typical AFL in 1 patient resulted in cycle length
oscillation. CONCLUSIONS: LLR is a subtype of right atrial flutter and depends on
conduction through the TA-ER isthmus.
PMID- 10190880
TI - Abnormal norepinephrine clearance and adrenergic receptor sensitivity in
idiopathic orthostatic intolerance.
AB - BACKGROUND: Chronic orthostatic intolerance (OI) is characterized by symptoms of
inadequate cerebral perfusion with standing, in the absence of significant
orthostatic hypotension. A heart rate increase of >/=30 bpm is typical. Possible
underlying pathophysiologies include hypovolemia, partial dysautonomia, or a
primary hyperadrenergic state. We tested the hypothesis that patients with OI
have functional abnormalities in autonomic neurons regulating cardiovascular
responses. METHODS AND RESULTS: Thirteen patients with chronic OI and 10 control
subjects underwent a battery of autonomic tests. Systemic norepinephrine (NE)
kinetics were determined with the patients supine and standing before and after
tyramine administration. In addition, baroreflex sensitivity, hemodynamic
responses to bolus injections of adrenergic agonists, and intrinsic heart rate
were determined. Resting supine NE spillover and clearance were similar in both
groups. With standing, patients had a greater decrease in NE clearance than
control subjects (55+/-5% versus 30+/-7%, P<0.02). After tyramine, NE spillover
did not change significantly in patients but increased 50+/-10% in control
subjects (P<0.001). The dose of isoproterenol required to increase heart rate 25
bpm was lower in patients than in control subjects (0.5+/-0.05 versus 1.0+/-0.1
microg, P<0.005), and the dose of phenylephrine required to increase systolic
blood pressure 25 mm Hg was lower in patients than control subjects (105+/-11
versus 210+/-12 microg, P<0.001). Baroreflex sensitivity was lower in patients
(12+/-1 versus 18+/-2 ms/mm Hg, P<0.02), but the intrinsic heart rate was similar
in both groups. CONCLUSIONS: The decreased NE clearance with standing, resistance
to the NE-releasing effect of tyramine, and increased sensitivity to adrenergic
agonists demonstrate dramatically disordered sympathetic cardiovascular
regulation in patients with chronic OI.
PMID- 10190881
TI - Augmented sympathetic activation during short-term hypoxia and high-altitude
exposure in subjects susceptible to high-altitude pulmonary edema.
AB - BACKGROUND: Pulmonary hypertension is a hallmark of high-altitude pulmonary edema
and may contribute to its pathogenesis. Cardiovascular adjustments to hypoxia are
mediated, at least in part, by the sympathetic nervous system, and sympathetic
activation promotes pulmonary vasoconstriction and alveolar fluid flooding in
experimental animals. METHODS AND RESULTS: We measured sympathetic nerve activity
(using intraneural microelectrodes) in 8 mountaineers susceptible to high
altitude pulmonary edema and 7 mountaineers resistant to this condition during
short-term hypoxic breathing at low altitude and at rest at a high-altitude
laboratory (4559 m). We also measured systolic pulmonary artery pressure to
examine the relationship between sympathetic activation and pulmonary
vasoconstriction. In subjects prone to pulmonary edema, short-term hypoxic
breathing at low altitude evoked comparable hypoxemia but a 2- to 3-times-larger
increase in the rate of the sympathetic nerve discharge than in subjects
resistant to edema (P<0.001). At high altitude, in subjects prone to edema, the
increase in the mean+/-SE sympathetic firing rate was >2 times larger than in
those resistant to edema (36+/-7 versus 15+/-4 bursts per minute, P<0.001) and
preceded the development of lung edema. We observed a direct relationship between
sympathetic nerve activity and pulmonary artery pressure measured at low and high
altitude in the 2 groups (r=0.83, P<0.0001). CONCLUSIONS: With the use of direct
measurements of postganglionic sympathetic nerve discharge, these data provide
the first evidence for an exaggerated sympathetic activation in subjects prone to
high-altitude pulmonary edema both during short-term hypoxic breathing at low
altitude and during actual high-altitude exposure. Sympathetic overactivation may
contribute to high-altitude pulmonary edema.
PMID- 10190882
TI - Hydrogen peroxide, potassium currents, and membrane potential in human
endothelial cells.
AB - BACKGROUND: Hydrogen peroxide (H2O2) and reactive oxygen species are implicated
in inflammation, ischemia-reperfusion injury, and atherosclerosis. The role of
ion channels has not been previously explored. METHODS AND RESULTS: K+ currents
and membrane potential were recorded in endothelial cells by voltage- and current
clamp techniques. H2O2 elicited both hyperpolarization and depolarization of the
membrane potential in a concentration-dependent manner. Low H2O2 concentrations
(0.01 to 0.25 micromol/L) inhibited the inward-rectifying K+ current (KIR). Whole
cell K+ current analysis revealed that H2O2 (1 mmol/L) applied to the bath
solution increased the Ca2+-dependent K+ current (KCa) amplitude. H2O2 increased
KCa current in outside-out patches in a Ca2+-free solution. When catalase (5000
micro/mL) was added to the bath solution, the outward-rectifying K+ current
amplitude was restored. In contrast, superoxide dismutase (1000 u/mL) had only a
small effect on the H2O2-induced K+ current changes. Next, we measured whole-cell
K+ currents and redox potentials simultaneously with a novel redox potential
sensitive electrode. The H2O2-mediated KCa current increase was accompanied by a
whole-cell redox potential decrease. CONCLUSIONS: H2O2 elicited both
hyperpolarization and depolarization of the membrane potential through 2
different mechanisms. Low H2O2 concentrations inhibited inward-rectifying K+
currents, whereas higher H2O2 concentrations increased the amplitude of the
outward K+ current. We suggest that reactive oxygen species generated locally
increases the KCa current amplitude, whereas low H2O2 concentrations inhibit KIR
via intracellular messengers.
PMID- 10190883
TI - Angiogenesis inhibitors endostatin or TNP-470 reduce intimal neovascularization
and plaque growth in apolipoprotein E-deficient mice.
AB - BACKGROUND: Neovascularization within the intima of human atherosclerotic lesions
is well described, but its role in the progression of atherosclerosis is unknown.
In this report, we first demonstrate that intimal vessels occur in advanced
lesions of apolipoprotein E-deficient (apoE -/-) mice. To test the hypothesis
that intimal vessels promote atherosclerosis, we investigated the effect of
angiogenesis inhibitors on plaque growth in apoE -/- mice. METHODS AND RESULTS:
ApoE -/- mice were fed a 0.15% cholesterol diet. At age 20 weeks, mice were
divided into 3 groups and treated for 16 weeks as follows: group 1, recombinant
mouse endostatin, 20 mg. kg-1. d-1; group 2, fumagillin analogue TNP-470, 30
mg/kg every other day; and group 3, control animals that received a similar
volume of buffer. Average cholesterol levels were similar in all groups. Plaque
areas were quantified at the aortic origin. Median plaque area before treatment
was 0.250 mm2 (range, 0.170 to 0.348; n=10). Median plaque areas were 0.321
(0.238 to 0.412; n=10), 0.402 (0.248 to 0.533; n=15), and 0.751 mm2 (0.503 to
0.838; n=12) for the endostatin, TNP-470, and control groups, respectively
(P=0.0001). Therefore, endostatin and TNP-470 inhibited plaque growth during
the treatment period by 85% and 70%. Intimal smooth muscle cell contents of
plaques from control and treated mice were similar. CONCLUSIONS: Prolonged
treatment with either angiogenesis inhibitor reduced plaque growth and intimal
neovascularization in apoE -/- mice. Although the mechanism of plaque inhibition
induced by these agents is not established, these results suggest that intimal
neovascularization may promote plaque development.
PMID- 10190884
TI - Proatherogenic and antiatherogenic effects of probucol and phytosterols in
apolipoprotein E-deficient mice: possible mechanisms of action.
AB - BACKGROUND: The effects of probucol and a phytosterol mixture (FCP-3PI) on
atherosclerotic lesion formation, plasma lipoproteins, hepatic and lipoprotein
lipase activities, antioxidant enzyme activities, and plasma fibrinogen were
investigated in apolipoprotein E-knockout (apoE-KO) mice. METHODS AND RESULTS:
Three groups of 8 mice were fed a diet containing 9% (wt/wt) fat (controls) or
the foregoing diet supplemented with either 1% (wt/wt) probucol (the probucol
group) or 2% (wt/wt) FCP-3PI (the FCP-3PI group) for 20 weeks. Compared with
controls, atherosclerotic lesion size was 3 times greater in the probucol group,
whereas it was decreased by half in the FCP-3PI group. Probucol treatment
resulted in high plasma probucol concentrations, which correlated (r=0.69) with
the lesion area. HDL cholesterol was reduced (>75%) in the probucol group and
slightly increased (14%) in the FCP-3PI-treated group. Postheparin lipoprotein
lipase (LPL) activity was significantly reduced in both treatment groups, but
only FCP-3PI significantly decreased hepatic lipase activity. Plasma fibrinogen
was increased 42% by probucol and decreased 19% by FCP-3PI relative to controls.
Probucol significantly increased plasma glutathione reductase, glutathione
peroxidase, and superoxide dismutase activities (P<0.05). In contrast to findings
in apoE-KO mice, there was no probucol-induced atherosclerosis in their wild-type
counterparts fed the same dose for the same period of time. CONCLUSIONS:
Antiatherogenic activity of FCP-3PI in apoE-KO mice is associated with an
increase in HDL cholesterol concentration along with decreases in hepatic lipase
activity and plasma fibrinogen concentrations. Proatherogenic effects of probucol
may be related to increased plasma fibrinogen, decreased HDL cholesterol
concentrations along with decreased LPL activity, or its direct "toxicity" due to
very high plasma concentration. Our studies demonstrate that the antioxidant and
cholesterol-lowering properties of probucol do not prevent atherogenesis in this
particular animal model.
PMID- 10190885
TI - Intraperitoneal administration of anti-c-fms monoclonal antibody prevents initial
events of atherogenesis but does not reduce the size of advanced lesions in
apolipoprotein E-deficient mice.
AB - BACKGROUND: Atherosclerosis results from complex inflammatory-fibroproliferative
responses. To elucidate the central role of macrophage and macrophage-colony
stimulating factor (M-CSF) during atherogenesis, we used a new strategy to
administer to adult apolipoprotein E (apoE)-deficient mice a monoclonal antibody
(AFS98) raised against c-fms, the receptor of M-CSF. METHODS AND RESULTS: When 6
week-old apoE-deficient mice were fed a high-fat diet and injected with 2 mg of
AFS98 intraperitoneally on alternate days for 6 weeks, accumulation of macrophage
derived foam cells in the aortic root was suppressed by 70% compared with that in
controls. This preventive effect was associated with neither remarkable decrease
of the number of circulating monocytes nor systemic growth retardation. In
contrast, when apoE-deficient mice that had been fed a high-fat diet from 6 weeks
of age were given AFS98 from 12 to 18 weeks of age, a minimal protective effect
on lesion size was observed. CONCLUSIONS: These results suggest that (1)
macrophage and M-CSF/c-fms play an essential role in the arterial wall during
development of the fatty streak lesion and (2) blockade of the M-CSF/c-fms
pathway could act as protection from at least early atherogenesis but could have
a less preventive effect on maintenance of the advanced lesions.
PMID- 10190886
TI - Chronic endothelin receptor antagonism preserves coronary endothelial function in
experimental hypercholesterolemia.
AB - BACKGROUND: Endothelin-1 (ET-1) is an endothelium-derived peptide that constricts
coronary vessels through stimulation of the ET-A and ET-B receptors. Experimental
porcine hypercholesterolemia is associated with impaired coronary endothelial
function and elevated ET-1 concentrations. This study was designed to test the
hypothesis that chronic endothelin receptor antagonism preserves coronary
endothelial function in experimental hypercholesterolemia. METHODS AND RESULTS:
Acetylcholine (10(-6) to 10(-4) mol/L) was serially infused into the left
anterior descending coronary artery in pigs at baseline and after 12 weeks of a
high-cholesterol diet. In the interim, the animals were randomized to 3 groups:
Group 1 received no therapy, group 2 received 3 mg/kg per day RO 48-5695, a
combined ET-A/ET-B receptor antagonist, and group 3 received 4 mg/kg per day ABT
627, a selective ET-A receptor antagonist. Percent change in coronary artery
diameter, coronary blood flow, and coronary vascular resistance were calculated
on the basis of quantitative coronary angiography and intracoronary Doppler. At
12 weeks, total cholesterol was significantly and similarly increased in all
groups. Chronic endothelin receptor antagonism significantly increased coronary
blood flow in response to acetylcholine at 12 weeks (group 1: -41.6%+/-10.7%,
group 2: -4.7%+/-11.9%, group 3: 11.4%+/-7.4%). CONCLUSIONS: Chronic endothelin
receptor antagonism preserves coronary endothelial function in experimental
hypercholesterolemia. This study supports the role for ET-1 in the pathogenesis
of endothelial function. Moreover, endothelin receptor antagonists may have a
therapeutic role by maintaining coronary endothelial function in
pathophysiological states.
PMID- 10190887
TI - LDL increases inactive tissue factor on vascular smooth muscle cell surfaces:
hydrogen peroxide activates latent cell surface tissue factor.
AB - BACKGROUND: Tissue factor, which is required for the initiation of the extrinsic
coagulation cascade, is known to be upregulated in cells within atherosclerotic
lesions, including smooth muscle cells. Tissue factor expression on the smooth
muscle cell surface could be of pathological significance as a contributor to
plaque growth, thrombus formation, and the acute coronary syndrome after plaque
rupture. METHODS AND RESULTS: In this study, we show that LDL increased tissue
factor mRNA and cell surface protein in smooth muscle cells without a marked
increase in surface tissue factor activity. Hydrogen peroxide activated tissue
factor on the cell surface but did not increase tissue factor mRNA or cell
surface protein. Sequentially added LDL and hydrogen peroxide increased mRNA,
cell surface protein, and activity; surface activity was greater than that
observed with hydrogen peroxide alone. The action of hydrogen peroxide did not
involve a regulatory mechanism associated with the cytoplasmic tail of tissue
factor because a truncated tissue factor lacking the cytoplasmic tail was
activated by hydrogen peroxide. CONCLUSIONS: These results suggest a novel 2-step
pathway for increased tissue factor activity on smooth muscle cell surfaces in
which lipoproteins regulate synthesis of a latent tissue factor and oxidants
activate the protein complex.
PMID- 10190888
TI - Investigating feed-forward neural regulation of circulation from analysis of
spontaneous arterial pressure and heart rate fluctuations.
AB - BACKGROUND: Analysis of spontaneous fluctuations in systolic arterial pressure
(SAP) and pulse interval (PI) reveals the occurrence of sequences of consecutive
beats characterized by SAP and PI changing in the same (+PI/+SAP and -PI/-SAP) or
opposite (-PI/+SAP and +PI/-SAP) direction. Although the former reflects
baroreflex regulatory mechanisms, the physiological meaning of -PI/+SAP and +PI/
SAP is unclear. We tested the hypothesis that -PI/+SAP and +PI/-SAP
"nonbaroreflex" sequences represent a phenomenon modulated by the autonomic
nervous system reflecting a feed-forward mechanism of cardiovascular regulation.
METHODS AND RESULTS: We studied anesthetized rabbits before and after (1)
complete autonomic blockade (guanethidine+propranolol+atropine, n=13; CAB), (2)
sympathetic blockade (guanethidine+propranolol, n=15; SB), (3) parasympathetic
blockade (atropine, n=16), (4) sinoaortic denervation (n=10; SAD), and (5)
controlled respiration (n=10; CR). Nonbaroreflex sequences were defined as >/=3
beats in which SAP and PI of the following beat changed in the opposite
direction. CAB reduced the number of nonbaroreflex sequences (19. 1+/-12.3 versus
88.7+/-36.6, P<0.05), as did SB (25.3+/-11.7 versus 84.6+/-23.9, P<0.001) and
atropine (11.2+/-6.8 versus 94.1+/-32.4, P<0.05). SB concomitantly increased
baroreflex sensitivity (1.18+/-0. 11 versus 0.47+/-0.09 ms/mm Hg, P<0.01). SAD
and CR did not significantly affect their occurrence. CONCLUSIONS: These results
suggest that nonbaroreflex sequences represent the expression of an integrated,
neurally mediated, feed-forward type of short-term cardiovascular regulation able
to interact dynamically with the feedback mechanisms of baroreflex origin in the
control of heart period.
PMID- 10190889
TI - Relationship of therapeutic improvements and 28-day case fatality in patients
hospitalized with acute myocardial infarction between 1978 and 1993 in the
REGICOR study, Gerona, Spain. The REGICOR Investigators.
AB - BACKGROUND: The aim of this study was to analyze 28-day case fatality trends
between 1978 and 1993 among hospitalized acute myocardial infarction (AMI)
patients in the REGICOR registry, Gerona, Spain, and relate them to thrombolytic
and antiplatelet drug use and changes in patient characteristics. METHODS AND
RESULTS: A total of 2053 consecutive patients 25 to 74 years of age with a first
Q-wave AMI admitted to the reference hospital between 1978 and 1993 were
registered. Clinical characteristics and patient management were recorded. Four 4
year periods were considered: 1978 to 1981, 1982 to 1985 (prethrombolytic
therapy), 1986 to 1989 (thrombolytic and antiplatelet drugs introduced), and 1990
to 1993 (thrombolytic and antiplatelet drugs used routinely). The end point was
death at 28 days. Case fatality at 28 days decreased 6% per year between 1978 and
1993. A logistic model adjusted for comorbidity and severity showed the last 3
periods to present a steep decrease in the OR of death at 28 days: 0.86 (95% CI,
0.52 to 1.41), 0.59 (95% CI, 0.35 to 0.99), and 0.40 (95% CI, 0.24 to 0.69),
respectively, compared with the first period. After 1986, 85.7% of the 112 lives
saved could be attributed to the use of antiplatelet and thrombolytic drugs.
Adjusted relative risk reduction was 56.0% for antiplatelet drugs, 34.1% for
thrombolytic drugs, and 77.9% for the 2 combined. CONCLUSIONS: Our results
strongly suggest that new therapies introduced since 1986 have contributed to the
decrease in 28-day case fatality of patients admitted with a first Q-wave AMI.
This decrease could be attributable mainly to the use of antiplatelet and
thrombolytic drugs. These findings should encourage the routine use of
thrombolytic and antiplatelet drugs and particularly their combination in the
acute phase of AMI.
PMID- 10190890
TI - Images in cardiovascular medicine. Myocardial ischemia and occult coronary artery
disease.
PMID- 10190891
TI - TRANCE-RANK, a new signal pathway involved in lymphocyte development and T cell
activation.
PMID- 10190892
TI - Absence of "original antigenic sin" in autoimmunity provides an unforeseen
platform for immune therapy.
PMID- 10190893
TI - TRANCE, a tumor necrosis factor family member critical for CD40 ligand
independent T helper cell activation.
AB - CD40 ligand (CD40L), a tumor necrosis factor (TNF) family member, plays a
critical role in antigen-specific T cell responses in vivo. CD40L expressed on
activated CD4(+) T cells stimulates antigen-presenting cells such as dendritic
cells, resulting in the upregulation of costimulatory molecules and the
production of various inflammatory cytokines required for CD4(+) T cell priming
in vivo. However, CD40L- or CD40-deficient mice challenged with viruses mount
protective CD4(+) T cell responses that produce normal levels of interferon
gamma, suggesting a CD40L/CD40-independent mechanism of CD4(+) T cell priming
that to date has not been elucidated. Here we show that CD4(+) T cell responses
to viral infection were greatly diminished in CD40-deficient mice by
administration of a soluble form of TNF-related activation-induced cytokine
receptor (TRANCE-R) to inhibit the function of another TNF family member, TRANCE.
Thus, the TRANCE/TRANCE-R interaction provides costimulation required for
efficient CD4(+) T cell priming during viral infection in the absence of
CD40L/CD40. These results also indicate that not even the potent inflammatory
microenvironment induced by viral infections is sufficient to elicit efficient
CD4(+) T cell priming without proper costimulation provided by the TNF family
(CD40L or TRANCE). Moreover, the data suggest that TRANCE/TRANCE-R may be a novel
and important target for immune intervention.
PMID- 10190894
TI - Spontaneous regression of primary autoreactivity during chronic progression of
experimental autoimmune encephalomyelitis and multiple sclerosis.
AB - Experimental autoimmune encephalomyelitis (EAE) is a widely used animal model for
multiple sclerosis (MS). EAE is typically initiated by CD4(+) T helper cell type
1 (Th1) autoreactivity directed against a single priming immunodominant myelin
peptide determinant. Recent studies have shown that clinical progression of EAE
involves the accumulation of neo-autoreactivity, commonly referred to as epitope
spreading, directed against peptide determinants not involved in the priming
process. This study directly addresses the relative roles of primary
autoreactivity and secondary epitope spreading in the progression of both EAE and
MS. To this end we serially evaluated the development of several epitope
spreading cascades in SWXJ mice primed with distinctly different encephalitogenic
determinants of myelin proteolipid protein. In a series of analogous experiments,
we examined the development of epitope spreading in patients with isolated
monosymptomatic demyelinating syndrome as their disease progressed to clinically
definite MS. Our results indicate that in both EAE and MS, primary proliferative
autoreactivity associated with onset of clinical disease invariably regresses
with time and is often undetectable during periods of disease progression. In
contrast, the emergence of sustained secondary autoreactivity to spreading
determinants is consistently associated with disease progression in both EAE and
MS. Our results indicate that chronic progression of EAE and MS involves a
shifting of autoreactivity from primary initiating self-determinants to defined
cascades of secondary determinants that sustain the self-recognition process
during disease progression.
PMID- 10190895
TI - Retinoic acid and arsenic synergize to eradicate leukemic cells in a mouse model
of acute promyelocytic leukemia.
AB - In acute promyelocytic leukemia (APL) patients, retinoic acid (RA) triggers
differentiation while arsenic trioxide (arsenic) induces both a partial
differentiation and apoptosis. Although their mechanisms of action are believed
to be distinct, these two drugs both induce the catabolism of the oncogenic
promyelocytic leukemia (PML)/RARalpha fusion protein. While APL cell lines
resistant to one agent are sensitive to the other, the benefit of combining RA
and arsenic in cell culture is controversial, and thus far, no data are available
in patients. Using syngenic grafts of leukemic blasts from PML/RARalpha
transgenic mice as a model for APL, we demonstrate that arsenic induces apoptosis
and modest differentiation, and prolongs mouse survival. Furthermore, combining
arsenic with RA accelerates tumor regression through enhanced differentiation and
apoptosis. Although RA or arsenic alone only prolongs survival two- to threefold,
associating the two drugs leads to tumor clearance after a 9-mo relapse-free
period. These studies establishing RA/arsenic synergy in vivo prompt the use of
combined arsenic/RA treatments in APL patients and exemplify how mouse models of
human leukemia can be used to design or optimize therapies.
PMID- 10190896
TI - In autoimmune diabetes the transition from benign to pernicious insulitis
requires an islet cell response to tumor necrosis factor alpha.
AB - The islet-infiltrating and disease-causing leukocytes that are a hallmark of
insulin-dependent diabetes mellitus produce and respond to a set of cytokine
molecules. Of these, interleukin 1beta, tumor necrosis factor (TNF)-alpha, and
interferon (IFN)-gamma are perhaps the most important. However, as pleiotropic
molecules, they can impact the path leading to beta cell apoptosis and diabetes
at multiple points. To understand how these cytokines influence both the
formative and effector phases of insulitis, it is critical to determine their
effects on the assorted cell types comprising the lesion: the effector T cells,
antigen-presenting cells, vascular endothelium, and target islet tissue. Here, we
report using nonobese diabetic chimeric mice harboring islets deficient in
specific cytokine receptors or cytokine-induced effector molecules to assess how
these compartmentalized loss-of-function mutations alter the events leading to
diabetes. We found that islets deficient in Fas, IFN-gamma receptor, or inducible
nitric oxide synthase had normal diabetes development; however, the specific lack
of TNF- alpha receptor 1 (p55) afforded islets a profound protection from disease
by altering the ability of islet-reactive, CD4(+) T cells to establish insulitis
and subsequently destroy islet beta cells. These results argue that islet cells
play a TNF-alpha-dependent role in their own demise.
PMID- 10190897
TI - Fas gene mutation in the progression of adult T cell leukemia.
AB - Fas antigen (Apo-1/CD95) is an apoptosis-signaling cell surface receptor
belonging to the tumor necrosis factor receptor superfamily. Adult T cell
leukemia (ATL) cells express Fas antigen and show apoptosis after treatment with
an anti-Fas monoclonal antibody. We established the ATL cell line KOB, which
showed resistance to Fas-mediated apoptosis, and found that KOB expressed two
forms of Fas mRNA, the normal form and a truncated form. The truncated transcript
lacked 20 base pairs at exon 9, resulting in a frame shift and the generation of
a premature stop codon at amino acid 239. The same mutation was detected in
primary ascitic cells and peripheral blood cells. The mutation was not detected
in lymph node cells, however, although all of the primary ATL cells were of the
same clonal origin. A retroviral-mediated gene transfer of the truncated Fas to
Jurkat cells rendered the cells resistant to Fas-mediated apoptosis, suggesting a
dominant negative interference mechanism. These results indicate that an ATL
subclone acquires a Fas mutation in the lymph nodes, enabling the subclone to
escape from apoptosis mediated by the Fas/Fas ligand system and proliferate in
the body. Mutation of the Fas gene may be one of the mechanisms underlying the
progression of ATL.
PMID- 10190898
TI - Bone marrow NK1.1(-) and NK1.1(+) T cells reciprocally regulate acute graft
versus host disease.
AB - Sorted CD4(+) and CD8(+) T cells from the peripheral blood or bone marrow of
donor C57BL/6 (H-2(b)) mice were tested for their capacity to induce graft-versus
host disease (GVHD) by injecting the cells, along with stringently T cell
depleted donor marrow cells, into lethally irradiated BALB/c (H-2(d)) host mice.
The peripheral blood T cells were at least 30 times more potent than the marrow T
cells in inducing lethal GVHD. As NK1.1(+) T cells represented <1% of all T cells
in the blood and approximately 30% of T cells in the marrow, the capacity of
sorted marrow NK1.1(-) CD4(+) and CD8(+) T cells to induce GVHD was tested. The
latter cells had markedly increased potency, and adding back marrow NK1.1(+) T
cells suppressed GVHD. The marrow NK1.1(+) T cells secreted high levels of both
interferon gamma (IFN-gamma) and interleukin 4 (IL-4), and the NK1.1(-) T cells
secreted high levels of IFN-gamma with little IL-4. Marrow NK1.1(+) T cells
obtained from IL-4(-/-) rather than wild-type C57BL/6 donors not only failed to
prevent GVHD but actually increased its severity. Together, these results
demonstrate that GVHD is reciprocally regulated by the NK1.1(-) and NK1.1(+) T
cell subsets via their differential production of cytokines.
PMID- 10190899
TI - Effector cells of both nonhemopoietic and hemopoietic origin are required for
interferon (IFN)-gamma- and tumor necrosis factor (TNF)-alpha-dependent host
resistance to the intracellular pathogen, Toxoplasma gondii.
AB - Although interferon (IFN)-gamma-activated, mononuclear phagocytes are considered
to be the major effectors of resistance to intracellular pathogens, it is unclear
how they control the growth of microorganisms that reside in nonhemopoietic
cells. Pathogens within such cells may be killed by metabolites secreted by
activated macrophages or, alternatively, directly controlled by cytokine-induced
microbicidal mechanisms triggered within infected nonphagocytic cells. To
distinguish between these two basic mechanisms of cell-mediated immunity,
reciprocal bone marrow chimeras were constructed between wild-type and IFN-gamma
receptor-deficient mice and their survival assessed following infection with
Toxoplasma gondii, a protozoan parasite that invades both hemopoietic and
nonhemopoietic cell lineages. Resistance to acute and persistent infection was
displayed only by animals in which IFN-gamma receptors were expressed in both
cellular compartments. Parallel chimera experiments performed with tumor necrosis
factor (TNF) receptor-deficient mice also indicated a codependence on hemopoietic
and nonhemopoietic lineages for optimal control of the parasite. In contrast, in
mice chimeric for inducible nitric oxide synthase (iNOS), an enzyme associated
with IFN-gamma-induced macrophage microbicidal activity, expression by cells of
hemopoietic origin was sufficient for host resistance. Together, these findings
suggest that, in concert with bone marrow-derived effectors, nonhemopoietic cells
can directly mediate, in the absence of endogenous iNOS, IFN-gamma- and TNF-alpha
dependent host resistance to intracellular infection.
PMID- 10190900
TI - A human histocompatibility leukocyte antigen (HLA)-G-specific receptor expressed
on all natural killer cells.
AB - Human natural killer (NK) cells express several killer cell immunoglobulin (Ig)
like receptors (KIRs) that inhibit their cytotoxicity upon recognition of human
histocompatibility leukocyte antigen (HLA) class I molecules on target cells.
Additional members of the KIR family, including some that deliver activation
signals, have unknown ligand specificity and function. One such KIR, denoted
KIR2DL4, is structurally divergent from other KIRs in the configuration of its
two extracellular Ig domains and of its transmembrane and cytoplasmic domains.
Here we show that recombinant soluble KIR2DL4 binds to cells expressing HLA-G but
not to cells expressing other HLA class I molecules. Unlike other HLA class I
specific KIRs, which are clonally distributed on NK cells, KIR2DL4 is expressed
at the surface of all NK cells. Furthermore, functional transfer of KIR2DL4 into
the cell line NK-92 resulted in inhibition of lysis of target cells that express
HLA-G, but not target cells that express other class I molecules including HLA-E.
Therefore, given that HLA-G expression is restricted to fetal trophoblast cells,
KIR2DL4 may provide important signals to maternal NK decidual cells that interact
with trophoblast cells at the maternal-fetal interface during pregnancy.
PMID- 10190901
TI - A novel cytoplasmic protein with RNA-binding motifs is an autoantigen in human
hepatocellular carcinoma.
AB - In hepatocellular carcinoma (HCC), autoantibodies to intracellular antigens are
detected in 30-40% of patients. Patients with chronic hepatitis or liver
cirrhosis develop HCC, and when this occurs, some patients exhibit autoantibodies
of new specificities. It has been suggested that these novel autoantibody
responses may be immune system reactions to proteins involved in transformation
associated cellular events. One HCC serum shown to contain antibodies to
unidentified cellular antigens was used to immunoscreen a cDNA expression
library, and a full length cDNA clone was isolated with an open reading frame
encoding 556 amino acids with a predicted molecular mass of 62 kD. The 62-kD
protein contained two types of RNA-binding motifs, the consensus sequence RNA
binding domain (CS-RBD) and four hnRNP K homology (KH) domains. This protein,
provisionally called p62, has close identity (66-70%) to three other proteins at
the amino acid sequence level, and all four proteins may belong to a family
having CS-RBD in the NH2-terminal region and four KH domains in the mid-to-COOH-
terminal region. The homologous proteins are: KH domain-containing protein
overexpressed in cancer (Koc); zipcode binding protein, a protein which binds to
a conserved nucleotide element in chicken beta-actin mRNA (ZBP1); and a protein
which binds to a promoter cis element in Xenopus laevis TFIIIA gene (B3). p62
protein is cytoplasmic in location, and autoantibodies were found in 21% of a
cohort of HCC patients. Patients with chronic hepatitis and liver cirrhosis,
conditions which are frequent precursors to HCC, were negative for these
autoantibodies, suggesting that the immune response might be related to cellular
events leading to transformation. However, the possible involvement of p62
autoantigen as a factor in the transformation process remains to be elucidated.
PMID- 10190902
TI - Altered ligands reveal limited plasticity in the T cell response to a pathogenic
epitope.
AB - Experimental leishmaniasis offers a well characterized model of T helper type 1
cell (Th1)-mediated control of infection by an intracellular organism.
Susceptible BALB/c mice aberrantly develop Th2 cells in response to infection and
are unable to control parasite dissemination. The early CD4(+) T cell response in
these mice is oligoclonal and reflects the expansion of Vbeta4/ Valpha8-bearing T
cells in response to a single epitope from the parasite Leishmania homologue of
mammalian RACK1 (LACK) antigen. Interleukin 4 (IL-4) generated by these cells is
believed to direct the subsequent Th2 response. We used T cells from T cell
receptor-transgenic mice expressing such a Vbeta4/Valpha8 receptor to
characterize altered peptide ligands with similar affinity for I-Ad. Such altered
ligands failed to activate IL-4 production from transgenic LACK-specific T cells
or following injection into BALB/c mice. Pretreatment of susceptible mice with
altered peptide ligands substantially altered the course of subsequent infection.
The ability to confer a healer phenotype on otherwise susceptible mice using
altered peptides that differed by a single amino acid suggests limited diversity
in the endogenous T cell repertoire recognizing this antigen.
PMID- 10190903
TI - The natural killer T (NKT) cell ligand alpha-galactosylceramide demonstrates its
immunopotentiating effect by inducing interleukin (IL)-12 production by dendritic
cells and IL-12 receptor expression on NKT cells.
AB - The natural killer T (NKT) cell ligand alpha-galactosylceramide (alpha-GalCer)
exhibits profound antitumor activities in vivo that resemble interleukin (IL)-12
mediated antitumor activities. Because of these similarities between the
activities of alpha-GalCer and IL-12, we investigated the involvement of IL-12 in
the activation of NKT cells by alpha-GalCer. We first established, using purified
subsets of various lymphocyte populations, that alpha-GalCer selectively
activates NKT cells for production of interferon (IFN)-gamma. Production of IFN
gamma by NKT cells in response to alpha-GalCer required IL-12 produced by
dendritic cells (DCs) and direct contact between NKT cells and DCs through
CD40/CD40 ligand interactions. Moreover, alpha-GalCer strongly induced the
expression of IL-12 receptor on NKT cells from wild-type but not CD1(-/-) or
Valpha14(-/-) mice. This effect of alpha-GalCer required the production of IFN
gamma by NKT cells and production of IL-12 by DCs. Finally, we showed that
treatment of mice with suboptimal doses of alpha-GalCer together with suboptimal
doses of IL-12 resulted in strongly enhanced natural killing activity and IFN
gamma production. Collectively, these findings indicate an important role for DC
produced IL-12 in the activation of NKT cells by alpha-GalCer and suggest that
NKT cells may be able to condition DCs for subsequent immune responses. Our
results also suggest a novel approach for immunotherapy of cancer.
PMID- 10190904
TI - Defective interleukin (IL)-18-mediated natural killer and T helper cell type 1
responses in IL-1 receptor-associated kinase (IRAK)-deficient mice.
AB - Interleukin (IL)-18 is functionally similar to IL-12 in mediating T helper cell
type 1 (Th1) response and natural killer (NK) cell activity but is related to IL
1 in protein structure and signaling, including recruitment of IL-1 receptor
associated kinase (IRAK) to the receptor and activation of c-Jun NH2-terminal
kinase (JNK) and nuclear factor (NF)-kappaB. The role of IRAK in IL-18-induced
responses was studied in IRAK-deficient mice. Significant defects in JNK
induction and partial impairment in NF-kappaB activation were found in IRAK
deficient Th1 cells, resulting in a dramatic decrease in interferon (IFN)-gamma
mRNA expression. In vivo Th1 response to Propionibacterium acnes and
lipopolysaccharide in IFN-gamma production and induction of NK cytotoxicity by IL
18 were severely impaired in IRAK-deficient mice. IFN-gamma production by
activated NK cells in an acute murine cytomegalovirus infection was significantly
reduced despite normal induction of NK cytotoxicity. These results demonstrate
that IRAK plays an important role in IL-18-induced signaling and function.
PMID- 10190905
TI - Bone morphogenetic proteins regulate the developmental program of human
hematopoietic stem cells.
AB - The identification of molecules that regulate human hematopoietic stem cells has
focused mainly on cytokines, of which very few are known to act directly on stem
cells. Recent studies in lower organisms and the mouse have suggested that bone
morphogenetic proteins (BMPs) may play a critical role in the specification of
hematopoietic tissue from the mesodermal germ layer. Here we report that BMPs
regulate the proliferation and differentiation of highly purified primitive human
hematopoietic cells from adult and neonatal sources. Populations of rare
CD34(+)CD38(-)Lin- stem cells were isolated from human hematopoietic tissue and
were found to express the BMP type I receptors activin-like kinase (ALK)-3 and
ALK-6, and their downstream transducers SMAD-1, -4, and -5. Treatment of isolated
stem cell populations with soluble BMP-2, -4, and -7 induced dose-dependent
changes in proliferation, clonogenicity, cell surface phenotype, and multilineage
repopulation capacity after transplantation in nonobese diabetic/severe combined
immunodeficient (NOD/SCID) mice. Similar to transforming growth factor beta,
treatment of purified cells with BMP-2 or -7 at high concentrations inhibited
proliferation yet maintained the primitive CD34(+)CD38(-) phenotype and
repopulation capacity. In contrast, low concentrations of BMP-4 induced
proliferation and differentiation of CD34(+) CD38(-)Lin- cells, whereas at higher
concentrations BMP-4 extended the length of time that repopulation capacity could
be maintained in ex vivo culture, indicating a direct effect on stem cell
survival. The discovery that BMPs are capable of regulating repopulating cells
provides a new pathway for controlling human stem cell development and a powerful
model system for studying the biological mechanism of BMP action using primary
human cells.
PMID- 10190906
TI - Tetrameric complexes of human histocompatibility leukocyte antigen (HLA)-G bind
to peripheral blood myelomonocytic cells.
AB - The nonclassical MHC class I molecule human histocompatibility leukocyte antigen
(HLA)-G is selectively expressed on fetal trophoblast tissue at the maternal
fetal interface in pregnancy. It has long been suggested that HLA-G may inhibit
maternal natural killer (NK) cells through interaction with particular NK cell
receptors (KIRs). To investigate interactions of HLA-G, we constructed
phycoerythrin-labeled tetrameric complexes of HLA-G refolded with a self-peptide.
These HLA-G tetramers failed to bind to NK cells and cells transfected with
CD94/NKG2 and killer immunoglobulin-like NK receptors. In contrast, HLA-G
tetramers did bind to peripheral blood monocytes, staining a CD16(+)CD14(mid)
subset with greater intensity. On transfectants, HLA-G tetramers bound to
inhibitory immunoglobulin-like transcript (ILT)2 and ILT4 receptors. However,
staining in the presence of antibodies reactive with ILT receptors revealed that
the interaction of HLA-G tetramers with blood monocytes was largely due to
binding to ILT4. These results suggest that the primary role of HLA-G may be the
modulation of myelomonocytic cell behavior in pregnancy.
PMID- 10190907
TI - Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) can regulate dendritic cell
induced activation and cytotoxicity of CD8(+) T cells independently of CD4(+) T
cell help.
AB - The mechanisms that regulate the strength and duration of CD8(+) cytotoxic T cell
activity determine the effectiveness of an antitumor immune response. To better
understand the antitumor effects of anti-cytotoxic T lymphocyte-associated
antigen 4 (CTLA-4) antibody treatment, we analyzed the effect of CTLA-4 signaling
on CD8(+) T cells in vitro and in vivo. In vitro, cross-linking of CTLA-4 on
purified CD8(+) T cells caused decreased proliferative responses to anti-CD3
stimulation and rapid loss of activation marker expression. In vivo, blockade of
CTLA-4 by neutralizing anti-CTLA-4 mAb greatly enhanced the accumulation,
activation, and cytotoxic activity of CD8(+) T cells induced by immunization with
Ag on dendritic cells (DC). This enhanced response did not require the expression
of MHC class II molecules on DC or the presence of CD4(+) T cells. These results
demonstrate that CTLA-4 blockade is able to directly enhance the proliferation
and activation of specific CD8(+) T cells, indicating its potential for tumor
immunotherapy even in situations in which CD4(+) T cell help is limited or
absent.
PMID- 10190908
TI - ZAP-70 protein promotes tyrosine phosphorylation of T cell receptor signaling
motifs (ITAMs) in immature CD4(+)8(+) thymocytes with limiting p56(lck).
AB - As a result of interaction with epithelial cells in the thymic cortex, immature
CD4(+)8(+) (double positive, DP) thymocytes express relatively few T cell
receptors (TCRs) and contain diminished numbers of coreceptor-associated p56(lck)
(lck) PTK molecules. As a result, TCR signal transduction in DP thymocytes is
significantly impaired, despite its importance for repertoire selection. We
report here that, in DP thymocytes, tyrosine phosphorylation of TCR signaling
motifs (ITAMs) by lck, an early event in TCR signal transduction, is dependent
upon ZAP-70 protein independent of ZAP-70's kinase activity. Furthermore, the
dependence on ZAP-70 protein for ITAM phosphorylation diminishes as available lck
increases. Importantly, ZAP-70's role in ITAM phosphorylation in DP thymocytes is
not limited to protecting phosphorylated ITAMs from dephosphorylation. Rather,
this study indicates that ZAP-70 protein augments ITAM phosphorylation in DP
thymocytes and so compensates in part for the relative deficiency of coreceptor
associated lck.
PMID- 10190909
TI - Nitric oxide in acute hypoxic respiratory failure: from the bench to the bedside
and back again.
PMID- 10190910
TI - Neonatal hypoglycemia: a little goes a long way.
PMID- 10190911
TI - Intensive diabetes therapy in childhood: is it achievable? Is it desirable? Is it
safe?
PMID- 10190912
TI - Report of a workshop on the epidemiology, natural history, and pathogenesis of
chronic fatigue syndrome in adolescents.
PMID- 10190913
TI - Multicenter randomized controlled trial of the effects of inhaled nitric oxide
therapy on gas exchange in children with acute hypoxemic respiratory failure.
AB - OBJECTIVES AND BACKGROUND: To determine whether inhaled nitric oxide (iNO)
therapy can attenuate the progression of lung disease in acute hypoxemic
respiratory failure, we performed a multicenter, randomized, masked, controlled
study of the effects of prolonged iNO therapy on oxygenation. We hypothesized
that iNO therapy would improve oxygenation in an acute manner, slow the rate of
decline in gas exchange, and decrease the number of patients who meet pre
established oxygenation failure criteria. STUDY DESIGN: A total of 108 children
(median age 2.5 years) with severe acute hypoxemic respiratory failure from 7
centers were enrolled. After consent was obtained, patients were randomized to
treatment with iNO (10 ppm) or mechanical ventilation alone for at least 72
hours. Patients with an oxygenation index >/=40 for 3 hours or >/=25 for 6 hours
were considered treatment failures and exited the study. RESULTS: Patient age,
primary diagnosis, pediatric risk of mortality score, mode of ventilation, and
median oxygenation index (35 +/- 22 vs 30 +/- 15; iNO vs control; mean +/- SEM)
were not different between groups at study entry. Comparisons of oxygenation
indexes during the first 12 hours demonstrated an acute improvement in
oxygenation in the iNO group at 4 hours (-10.2 vs -2.7, mean values; P <.014) and
at 12 hours (-9.2 vs -2.8; P <.007). At 12 hours 36% of the control group met
failure criteria in contrast with 16% in the iNO group (P <.05). During prolonged
therapy the failure rate was reduced in the iNO group in patients whose entry
oxygenation index was >/=25 (P <.04) and in immunocompromised patients (P <.03).
CONCLUSIONS: We conclude that iNO causes an acute improvement in oxygenation in
children with severe AHRF. Two subgroups (immunocompromised and an entry oxygen
index >/=25) appear to have a more sustained improvement in oxygenation, and we
speculate that these subgroups may benefit from prolonged therapy.
PMID- 10190914
TI - Comparison of a beta-lactam alone versus beta-lactam and an aminoglycoside for
pulmonary exacerbation in cystic fibrosis.
AB - We determined whether a beta-lactam and an aminoglycoside have efficacy greater
than a beta-lactam alone in the management of a pulmonary exacerbation in
patients with cystic fibrosis. STUDY DESIGN: Azlocillin and placebo or azlocillin
and tobramycin were administered to 76 patients with a pulmonary exacerbation
caused by Pseudomonas aeruginosa in a randomized double-blind, third-party
monitored protocol. Improvement was assessed by standardized clinical evaluation,
pulmonary function testing, sputum bacterial density, sputum DNA content, and
time to the next pulmonary exacerbation requiring hospitalization. RESULTS: No
significant difference was seen between the 2 treatment groups in clinical
evaluation, sputum DNA concentration, forced vital capacity, forced expiratory
volume in second 1, or peak expiratory flow rate at the end of treatment (33
receiving azlocillin alone and 43 both antibiotics); adverse reactions were
equivalent in each group. Sputum P. aeruginosa density decreased more with
combination therapy (P =.034). On follow-up evaluation, an average of 26 days
after the end of treatment, all outcome indicators had worsened in both groups.
Time to readmission for a new pulmonary exacerbation was significantly longer in
the group receiving azlocillin plus tobramycin (P <.001). Treatment-emergent
tobramycin resistance occurred in both groups and was more frequent with
combination therapy. CONCLUSION: We conclude that the combination of a beta
lactam and an aminoglycoside produces a longer clinical remission than a beta
lactam alone and slightly better initial improvement.
PMID- 10190915
TI - Efficacy and safety of high-dose inhaled steroids in children with asthma: a
comparison of fluticasone propionate with budesonide.
AB - OBJECTIVE: To compare the efficacy and adverse effects of inhaled fluticasone
propionate (FP), 400 microgram/d, with those of budesonide (BUD), 800
microgram/d, in children with moderate to severe asthma. METHODS: Three hundred
thirty-three children, ages 4 to 12 years, receiving inhaled corticosteroids were
enrolled in a double-blind, double-dummy, randomized, parallel-group study. After
a 2-week run-in phase, 166 children received FP and 167 received BUD for 20
weeks. The primary outcome variable was mean morning peak expiratory flow; the 2
treatments were to be regarded as equivalent if the 90% CI for the treatment
difference was within +/- 15 L/min. Pulmonary function, height, and diary cards
were assessed at each visit; and morning serum cortisol levels were determined
before and after treatment. RESULTS: Baseline peak expiratory flow was similar,
FP 236 +/- 72 (SD) L/min and BUD 229 +/- 74, increasing after treatment to 277 +/
41 and 257 +/- 28, a difference between treatments of 12 L/min (90% CI 6-19
L/min; P =.002). Symptom control and use of rescue medication were the same.
Cortisol levels after treatment were 199 nmol/L (FP) and 183 nmol/L (BUD)
(treatment ratio = 1.09; 90% CI 0.98-1.21; P =.172). Linear growth was less in
those receiving BUD (mean difference, 6.2 mm; 95% CI 2.9-9.6; P =.0003).
CONCLUSION: FP at half the dose was superior to BUD in improving peak expiratory
flow and comparable in controlling symptoms. Growth was reduced with BUD compared
with FP, but there was no difference in serum cortisol suppression or hepatic or
renal function.
PMID- 10190916
TI - Five-year follow-up of neonates with reconstructed right common carotid arteries
after extracorporeal membrane oxygenation.
AB - OBJECTIVE: Serial Doppler ultrasonography and long-term neurodevelopmental follow
up outcomes were evaluated prospectively in neonates whose right common carotid
artery (RCCA) was reconstructed after extracorporeal membrane oxygenation (ECMO).
METHODS: Children with RCCA reconstruction (n = 34) were monitored for 3.5 to 4.5
years by Doppler ultrasonography for arterial patency, and 28 had IQ testing by 5
years. A comparison group consisted of 35 infants who had RCCA ligation after
ECMO. Neonatal electroencephalograms and computed tomography/magnetic resonance
imaging scans were also compared. RESULTS: Reconstructions were successful (<50%
RCCA stenosis by Doppler ultrasonography) in 26 (76%) of 34 children, 3 (9%) had
>/=50% stenosis, and 5 (15%) had occlusion. No significant differences were seen
between reconstructed and ligated groups in neonatal complications or ECMO
courses. Occurrence of marked neonatal electroencephalographic abnormalities did
not differ between groups. Abnormalities on computed tomography/magnetic
resonance imaging scans (4 of 31 vs 11 of 29, P =.025) and cerebral palsy (0 of
34 vs 5 of 35, P =.054) were more common in infants with RCCA ligation. No
differences were seen in developmental or IQ scores between the 2 groups, and 4
in each group had cognitive handicaps (at least 1 IQ score <70). CONCLUSIONS:
Most RCCA reconstructions remained patent, with 24% showing significant stenosis
or occlusion. Compared with a historical control group, patients with RCCA
reconstruction had fewer brain scan abnormalities and tended to be less likely to
have cerebral palsy. RCCA reconstruction after venoarterial ECMO may improve
outcome.
PMID- 10190917
TI - Trend in mortality from respiratory distress syndrome in the United States, 1970
1995.
AB - OBJECTIVE: We examined the trend in mortality caused by respiratory distress
syndrome (RDS) and its impact on changes in infant and neonatal mortality rates
(IMR, NMR) in the United States. STUDY DESIGN: Data on infant deaths in the
United States for the period 1970 through 1995 were used to compare RDS-specific
IMR to other cause-specific IMR. Data from the U.S. birth cohorts of 1985 through
1991 were used to examine birth weight- and RDS-specific NMRs. RESULTS: IMR from
RDS declined from 2.6 per 1000 live births in 1970 to 0.4 per 1000 in 1995. More
than three quarters of this decline occurred between 1970 and 1985. RDS-specific
NMR declined by 13% between 1985 and 1988 and by more than twofold greater, that
is, 28%, between 1988 and 1991. There was also a significant reduction in
postneonatal mortality from chronic lung diseases between 1988 and 1991.
CONCLUSIONS: Most of the reduction in mortality from RDS occurred before the
introduction of surfactant therapy. The recent accelerated reduction in mortality
from RDS between 1988 and 1991 was temporally associated with widespread use of
surfactant therapy and was the single most important factor for reduction in
overall NMR in the United States.
PMID- 10190918
TI - Gilbert's syndrome is a contributory factor in prolonged unconjugated
hyperbilirubinemia of the newborn.
AB - OBJECTIVE: Prolonged neonatal jaundice, beyond day 14 of life, is very common and
of concern to the clinician. The aim of this study was to investigate whether a
genetic mutation in the bilirubin UGT1A1 gene, which has been associated with
Gilbert's syndrome in adults, is a contributory factor in prolonged neonatal
jaundice. STUDY DESIGN: Blood was collected from 85 term newborns with
unexplained hyperbilirubinemia, and DNA was prepared. The neonates were divided
into 6 groups depending on whether they were breast-fed or bottle-fed and whether
they had acute, prolonged, or very prolonged jaundice. UGT1A1 TATA promoter
genotyping (DNA test for Gilbert's syndrome) was performed on all samples, and
analysis of the entire UGT1A1 coding sequence was performed in a representative
sample (11 of 26) of very prolonged cases. RESULTS: In addition to the known
common UGT1A1 TATA alleles (TA6 and TA7), a novel TATA allele (TA5) in a neonate
with very prolonged jaundice was identified. Statistical analysis of the TATA
genotype distributions within the group of breast-fed neonates revealed
significant differences among the acute, prolonged, and very prolonged subgroups
(.05 > P >.01): the incidence of familial hyperbilirubinemia genotypes (7/7 and
5/7) is 5 times greater in very prolonged cases (31%) relative to acute cases
(6%). Neonates with prolonged jaundice from family pedigrees were observed to
demonstrate the Gilbert's phenotype as children or young adults. CONCLUSIONS: A
genetic predisposition to develop prolonged neonatal hyperbilirubinemia in breast
fed infants is associated with TATA box polymorphism of the UGT1A1 gene and will
be recognized as Gilbert's syndrome in adulthood.
PMID- 10190919
TI - Serologic testing for inflammatory bowel disease.
AB - OBJECTIVES: To determine the accuracy of anti-neutrophil cytoplasmic antibodies
(ANCAs) and anti-Saccharomyces cerevisiae antibodies (ASCA) in distinguishing
patients with inflammatory bowel disease from patients with other disorders, seen
in a pediatric gastroenterology clinic setting, and in distinguishing ulcerative
colitis (UC) from Crohn's disease (CD). STUDY DESIGN: Serum samples from 120
children with new or established diagnoses of UC (n = 25) or CD (n = 20) and
control children (n = 74) were analyzed in blinded fashion for the presence of
IgG ANCAs and IgA and IgG ASCA. RESULTS: The highest sensitivity for detecting
inflammatory bowel disease, 71%, was achieved by using ANCAs and ASCA together.
The best test for UC was ANCAs, which had a sensitivity of 80%. However, the ANCA
pattern characteristic of UC, perinuclear ANCAs eliminated by DNAse, had a
sensitivity of 60%. High-titer ANCAs were specific for UC, whereas ASCA were
specific for CD. CONCLUSIONS: Testing for ANCAs and ASCA together did not achieve
sensitivity necessary for population screening. However, ANCAs and ASCA may be
helpful in evaluating children suspected of having inflammatory bowel disease and
in distinguishing UC from CD.
PMID- 10190920
TI - Serum IgE levels during the first 6 years of life.
AB - OBJECTIVE: Total serum IgE percentiles were derived for a population-based sample
of 4082 white children from Germany by weighted analysis of measurements from the
Multicenter Allergy Study cohort. METHODS: The children of a prospective birth
cohort were selected from a complete 1-year sample of newborns in 6 obstetric
departments in 1990. Total IgE was determined at 1, 2, 3, 5, and 6 years of age
in 1160 newborns of the cohort. By weighting these measurements for sex, atopic
family history, and elevated cord blood IgE, total serum IgE percentiles were
estimated for the original population-based sample of 4082 children. RESULTS: IgE
levels increased by age (P <.0001). We found statistically significant higher
total IgE values in boys than in girls at each age (P <.05). Within the group of
atopic children, this sex difference was not statistically significant.
CONCLUSION: Our estimates of total serum IgE levels for a large population-based
sample were lower than most values previously reported. We suggest that for both
clinical and epidemiologic and genetic studies, IgE values should be expressed
with percentiles.
PMID- 10190921
TI - Oral prednisolone is an effective adjuvant therapy for acute otitis media with
discharge through tympanostomy tubes.
AB - OBJECTIVE: To determine the efficacy of a short course of oral prednisolone as an
adjuvant therapy for acute otitis media draining through tympanostomy tubes.
STUDY DESIGN: In a randomized, double-blind, placebo-controlled study, children
with acute discharge (<48 hours) through tympanostomy tubes received either
prednisolone (2 mg/kg/d; n = 23) or placebo (n = 27) for 3 days. All children
received amoxicillin/clavulanate (40/10 mg/kg/d) for 7 days. The children were
examined daily at the study clinic until the drainage ceased. RESULTS: The median
duration of otorrhea in the prednisolone group was 1.0 days (25% to 75% range,
1.0 to 2.0 days), compared with 3.0 days (25% to 75% range, 2.0 to 4.0 days) in
the children receiving placebo (P <.001). The duration of otorrhea was =2 days
in 21 (91%) children in the prednisolone group, compared with 8 (30%) children in
the placebo group (P <.001). CONCLUSIONS: Oral prednisolone appears to be
modestly effective adjuvant therapy for acute otitis media with discharge through
tympanostomy tubes in children. Further studies seem warranted to determine
whether short-term use of steroids early during the course of acute otitis media
would also reduce the duration of middle ear effusion in children with intact
tympanic membranes.
PMID- 10190922
TI - Growth during maintenance hemodialysis: impact of enhanced nutrition and
clearance.
AB - Growth of children during maintenance hemodialysis has been reported to be
uniformly poor, with a mean annual loss of 0.4 to 0.8 SD in height. We adopted an
intensive program of closely monitored energy and protein intake with dialysis
urea clearances exceeding conventional recommendations. Twelve prepubertal or
early pubertal children (aged 7 months to 14 years) were monitored for an average
of 2.2 years (range 4 to 81 months) while receiving maintenance hemodialysis.
These children received an average of 90.6% and 155.9% of their recommended
energy and protein nutritional intake, respectively. With a prescribed urea
clearance of 5 mL/kg/min, we achieved a mean single treatment urea clearance
normalized for total body water of 2.00, a urea reduction ratio of 84.7%, and an
average time of hemodialysis of 14.8 h/wk, all well beyond current guidelines.
Over the course of dialysis treatment, the improvement in height SD score
was+0.31 SD/y (+0.32 excluding the 2 children treated with recombinant human
growth hormone). Normal growth was achieved without overt obesity and was
associated with normal pubertal growth spurt. These findings suggest that the
combination of increased dialysis and adequate nutrition can promote normal
growth in children treated with long-term hemodialysis.
PMID- 10190923
TI - Growth deficiency and malnutrition in Bloom syndrome.
AB - OBJECTIVES: To describe the growth and nutritional status of a pediatric
population with Bloom syndrome. STUDY DESIGN: Longitudinal growth data from 148
patients in the Bloom's Syndrome Registry (85 male, 63 female) were compiled
retrospectively from physician and parent records to develop graphed statistics
of weight-for-age, height-for-age, fronto-occipital circumference-for-age, and
weight-for-height for both sexes with comparisons with the normal population.
RESULTS: Term birth measurements confirm that the growth deficiency of Bloom
syndrome has prenatal onset. Stunting persists throughout life, and an adolescent
growth spurt is not apparent from the smoothed data. Growth continues by at least
1 cm/yr until age 21 years for both sexes. More than half of children with Bloom
syndrome are significantly wasted until age 8 years, which is not related to
early death or underlying malignancy. The mean body mass index for adults with
Bloom syndrome after age 25 years is low normal (n = 22, mean = 20.2 kg/m2).
CONCLUSIONS: Children with Bloom syndrome have significant growth retardation and
wasting.
PMID- 10190924
TI - Phenotypic spectrum and management issues in Kabuki syndrome.
AB - OBJECTIVE: To report the phenotypic spectrum and management issues of children
with Kabuki syndrome (Niikawa-Kuroki syndrome) from North America. DESIGN: A case
series of children (n = 18) with clinical findings of Kabuki syndrome. SETTING:
Medical genetics clinics in Washington, Alaska, and Arizona. RESULTS: Most
patients had postnatal growth retardation, and all had developmental delay and
hypotonia. Feeding difficulties, with or without cleft palate, were common; 5
patients required gastrostomy tube placement. Developmental quotients/IQs in all
but 2 were 60 or less. Seizures were seen in less than half of the patients, but
ophthalmologic and otologic problems were common, particularly recurrent otitis
media. Congenital heart defects were present in 7 (39%); 3 patients underwent
repair of coarctation of the aorta. Other features included urinary tract
anomalies, malabsorption, joint hypermobility and dislocation, congenital
hypothyroidism, idiopathic thrombocytopenic purpura, and in one patient,
autoimmune hemolytic anemia and hypogammaglobulinemia. All patients had negative
family histories for Kabuki syndrome. CONCLUSIONS: Kabuki syndrome is a mental
retardation-malformation syndrome affecting multiple organ systems, with a broad
spectrum of neuromuscular dysfunction and mental ability. Given that 18
ethnically diverse patients were identified from 2 genetics programs, it appears
that this syndrome is more common in North American non-Japanese patients than
previously appreciated.
PMID- 10190925
TI - Advanced glycation end products in children and adolescents with diabetes:
relation to glycemic control and early microvascular complications.
AB - OBJECTIVE: The measurement of serum advanced glycation end products (S-AGEs) in
children, adolescents, and young adults with diabetes to determine whether
increased S-AGE levels may be associated with long-term glycemic control and
early microvascular complications. STUDY DESIGN: The study was performed in (1)
178 children and adolescents with type 1 diabetes mellitus (age range, 2 to 21
years, onset before the age of 12 years; duration longer than 2 years) without
clinical and laboratory signs of microvascular complications, (2) 39 adolescents
and young adults (age range, 16.1 to 28.8 years) with background or
preproliferative retinopathy or persistent microalbuminuria, and (3) 98 healthy
age- and sex-matched control subjects. RESULTS: S-AGEs were significantly
increased in preschool and prepubertal children with diabetes and were
particularly elevated in pubertal subjects with diabetes compared with control
subjects. S-AGEs were markedly increased in adolescents with early microvascular
complications compared with both control subjects and diabetic patients without
retinopathy or nephropathy. No correlation was found between S-AGEs and albumin
excretion rate or blood pressure values. Glycated hemoglobulin values and S-AGEs
were significantly correlated (r = 0.32; P <.01). In children with poorly
controlled diabetes (HbA1 c >10%), long-term (2 years) improvement of glycemic
control resulted in a significant reduction of S-AGE levels in preschool and
prepubertal children, as well as in pubertal individuals. CONCLUSIONS: S-AGE
concentrations may be elevated even in preschool and prepubertal children with
diabetes; this means that the risk of microvascular complications may be present
at an early age. Improvement in glycemic control may be associated with a
significant decrease in S-AGEs.
PMID- 10190926
TI - Long-term effects of neonatal hypoglycemia on brain growth and psychomotor
development in small-for-gestational-age preterm infants.
AB - OBJECTIVE: To investigate the effects of neonatal hypoglycemia on physical growth
and neurocognitive function. STUDY DESIGN: A systematic detection of hypoglycemia
(<2.6 mmol/L or 47 mg/dL) was carried out in 85 small-for-gestational-age preterm
neonates. Prospective serial evaluations of physical growth and psychomotor
development were performed. Retrospectively, infants were grouped according to
their glycemic status. RESULTS: The incidence of hypoglycemia was 72.9%. Infants
with repeated episodes of hypoglycemia had significantly reduced head
circumferences and lower scores in specific psychometric tests at 3.5 years of
age. Hypoglycemia also caused reduced head circumferences at 18 months and lower
psychometric scores at 5 years of age. Infants with moderate recurrent
hypoglycemia had lower scores at 3.5 and 5 years of age compared with the group
of infants who had 1 single severe hypoglycemic episode. CONCLUSION: Recurrent
episodes of hypoglycemia were strongly correlated with persistent
neurodevelopmental and physical growth deficits until 5 years of age. Recurrent
hypoglycemia also was a more predictable factor for long-term effects than the
severity of a single hypoglycemic episode. Therefore repetitive blood glucose
monitoring and rapid treatment even for mild hypoglycemia are recommended for
small-for-gestational-age infants in the neonatal period.
PMID- 10190927
TI - Failure to detect preterm infants at risk of hypoglycemia before discharge.
AB - In a series of 79 consecutive preterm infants who were ready for discharge, 14
(18%) infants were unable to maintain normal concentrations of blood glucose.
This finding suggests that a significant number of preterm infants are at risk of
hypoglycemia at home if a feed is omitted or delayed.
PMID- 10190928
TI - The effect of hypoglycemic seizures on cognitive function in children with
diabetes: a 7-year prospective study.
AB - Sixteen children with insulin-dependent diabetes mellitus were evaluated at
diagnosis and after 1, 3, and 7 years. They showed significant declines in verbal
but not visuospatial abilities, particularly if they had any seizures from
hypoglycemia. At the 7-year assessment those with hypoglycemic seizures showed
deficits on perceptual, motor, memory, and attention tasks.
PMID- 10190929
TI - Antiperinuclear factor and antibodies to the stratum corneum of rat esophagus in
juvenile idiopathic arthritis.
AB - We analyzed the frequency and clinical correlates of antiperinuclear factor (APF)
and antibodies to the stratum corneum of rat esophagus in 86 children with
juvenile idiopathic arthritis (JIA), 32 children with juvenile systemic lupus
erythematosus, and 52 healthy children. Forty-two patients with JIA (49%) were
positive for APF. No association was observed between APF and current age, sex,
JIA subtype, age at disease onset, or disease duration. APF was found in one
patient with juvenile systemic lupus erythematosus and in no healthy child.
Antibodies to the stratum corneum of rat esophagus were detected in 3 patients
with polyarticular JIA. APF may be a valuable tool in the differential diagnosis
of JIA.
PMID- 10190930
TI - Unilateral total and contralateral partial pulmonary agenesis associated with
total anomalous pulmonary venous drainage.
AB - A term newborn presented with total right and partial left lung agenesis
associated with total anomalous obstructed left pulmonary venous drainage. This
unique association with a dramatic prognosis is thought to be due to a
developmental insult early in the embryonic formation of the lung and its
supporting vasculature.
PMID- 10190931
TI - Hemodynamic observations in a newborn with Parkes-Weber syndrome.
PMID- 10190932
TI - Clinical pathologic correlation: A 3-year-old boy with cystic fibrosis and
intestinal obstruction.
PMID- 10190934
TI - Reply.
PMID- 10190933
TI - Erythropoietin and iron therapy for preterm infants.
PMID- 10190935
TI - BMI: does it really reflect body fat mass?
PMID- 10190936
TI - High-dose aspirin in Kawasaki disease.
PMID- 10190937
TI - Welcome to never-neverland.
PMID- 10190939
TI - Potential clinical implications of early diagnosis of chronic myeloid leukemia.
PMID- 10190938
TI - Changes in adhesion molecule expression on lymphoblasts during acute
lymphoblastic leukemia treatment.
PMID- 10190940
TI - Hereditary thrombophilia as a multigenic condition.
PMID- 10190941
TI - Maturation and apoptosis of primary human acute myeloblastic leukemia cells are
determined by TNF-alpha exclusively through CD120A stimulation.
AB - BACKGROUND AND OBJECTIVE: Tumor necrosis factor-a plays an important role in
hematopoiesis. Its effects are mediated through two membrane-bound receptors: TNF
R I (p55; CD 120a) and TNF-R II (p75; CD 120b). The aim of our study was to
investigate the relative roles of these receptors. DESIGN AND METHODS: We
analyzed in 16 acute myeloid leukemia cases whether TNF-alpha could induce in
vitro maturation and apoptosis. We then investigated which of the two receptors
was provoking monocytic maturation and which was responsible for apoptosis by
using the agonistic MoAb HTR-9, directed at CD120a, and the CD120b antagonistic
MoAb UTR-1. RESULTS: Monocytic maturation (morphologic and immunologic) was
induced in all cases studied, although to different rates, by TNF-alpha and by
HTR-9 incubation. The addition of UTR-1 to TNF-alpha did not abolish maturation,
nor did it affect apoptosis, which was present in primary AML cultures after 4
and 10 days. INTERPRETATION AND CONCLUSIONS: We present here evidence that the
sole stimulation of CD 120a, but not of CD120b, by TNF-alpha is responsible for
bot monocytic maturation and apoptosis of primary AML blasts.
PMID- 10190942
TI - Genomic instability and recurrent breakpoints are main cytogenetic findings in
Hodgkin's disease.
AB - BACKGROUND AND OBJECTIVE: Successful cytogenetic studies in Hodgkin's disease
(HD) are rare, and, except for hyperdiploidy, no chromosome changes typical for
this disorder have been described. The purpose of this study was to collect
cytogenetic information from a new series of lymphoid neoplasms diagnosed either
as classical HD or as Hodgkin's-like anaplastic large cell lymphoma (HD-like
ALCL), according to the REAL Classification. DESIGN AND METHODS: We studied 27
cases of HD and 10 cases of HD-like ALCL. Cytogenetic investigations were
performed on lymph nodes (35 cases), bone marrow or pleural effusion. A large
screening of slides was performed to detect abnormal metaphases despite the low
mitotic index of Reed-Sternberg cells. In addition to ours, available published
data were analyzed in detail to identify recurring cytogenetic events. RESULTS:
Metaphases which could be analyzed were obtained in 86.5% of cases, with 59.4%
showing abnormal clones. We found a peculiar kind of cytogenetic instability in
which, despite variations in the type of structural rearrangements, chromosome
breakpoints were non-randomly distributed. Moreover, from our data plus those
collected from literature on HD (total 177 cases), the number of breakpoints was
higher in patients in a more advanced clinical stage. INTERPRETATION AND
CONCLUSIONS: Cytogenetic studies in HD are highly informative regarding
clonality, provided large numbers of metaphases are examined. Based on karyotype,
genetic changes in HD and HD-like ALCL are similar. Results are consistent with a
high degree of chromosomal instability and predominance of hyperdiploid complex
karyotypes. Chromosome breakpoints are non-randomly distributed and more numerous
in advanced clinical stages.
PMID- 10190943
TI - Changes in the fibrinolytic components of cultured human umbilical vein
endothelial cells induced by endotoxin, tumor necrosis factor-alpha and
interleukin-1alpha.
AB - BACKGROUND AND OBJECTIVE: Vascular fibrinolysis, a major natural defense
mechanism against thrombosis, is a highly regulated process. The aim of this
study was to evaluate the effect of endotoxin, tumor necrosis factor-alpha
(TNFalpha) and interleukin-1alpha (IL-1alpha), on the fibrinolytic potential of
cultured human umbilical vein endothelial cells (HUVEC). DESIGN AND METHODS:
Samples of stimulated conditioned media were collected over a period of 24 hours
to determine: plasminogen activator (PA) and plasminogen activator inhibitor
(PAI) activity, PAI-1 mRNA, tissue-type plasminogen activator (t-PA) antigen and
urokinase-type plasminogen activator (u-PA) antigen. RESULTS: Similar changes
were observed after endotoxin and cytokine stimulation: there was a significant
increase of PAI activity (p<0.01), starting at 6 hours, which remained 24 hours
after stimulation. PAI-1 mRNA also showed an important rise with these agents,
although cytokines induced an earlier and more intense inhibitor response (up to
6-fold increase). PA activity increased significantly at 6 hours (p<0.01) to drop
at 24 hours and was mainly related to the presence of u-PA. INTERPRETATION AND
CONCLUSIONS: We conclude that endotoxin,+TNFalpha and IL-1alpha induce profound
alterations in the fibrinolytic potential of HUVEC, characterized by an initial
rise of activators (u-PA) followed by a strong increase of PAI-1. These changes
may be of pathophysiologic significance for thrombosis and inflammatory
reactions.
PMID- 10190944
TI - Patients with thrombocytosis have normal or slightly elevated thrombopoietin
levels.
AB - BACKGROUND AND OBJECTIVE: The distinction between clonal and reactive
thrombocytoses is a frequent problem and implies different therapeutic options.
As thrombopoietin (TPO) is the main regulator of megakaryocytopoiesis and
thrombopoiesis, we measured TPO levels in patients with thrombocytosis in an
attempt to understand the regulation and potential utility of distinguishing
thrombocytoses. DESIGN AND METHODS: Serum TPO levels, platelet counts, mean
platelet volume, hemoglobin, erythrocyte sedimentation rate and age were
evaluated in 25 patients with clonal thrombocytosis (15 with essential
thrombocythemia, 6 with polycythemia vera and 4 with chronic myeloid leukemia)
and in 50 patients with reactive thrombocytosis distributed in three groups: 1)
patients in post-surgical states; 2) patients with solid tumors; and 3) patients
with inflammatory diseases. RESULTS: TPO levels were slightly increased in
patients with clonal (135+/-50 pg/mL) and reactive (147+/-58 pg/mL)
thrombocytosis compared with controls (121+/-58 pg/mL). Analyzing the different
groups, patients with essential thrombocythemia had the lowest TPO levels (120+/
28 pg/mL) and patients with solid tumors the highest levels (162+/-59 pg/mL).
Patients with clonal thrombocytosis were older, had higher platelet counts, mean
platelet volume and hemoglobin, and lower erythrocyte sedimentation rate than
patients with reactive thrombocytosis. INTERPRETATION AND CONCLUSIONS: Minor
differences were observed in TPO levels between patients with primary and
secondary thrombocytoses. Erythrocyte sedimentation rate, but not TPO levels, may
be a useful tool for discriminating both types of thrombocytoses.
PMID- 10190946
TI - The changing profile of Ph-positive chronic myeloid leukemia at presentation:
possible impact of earlier diagnosis on survival.
AB - BACKGROUND AND OBJECTIVE: Although there are indications that the profile of
chronic myeloid leukemia (CML) at presentation has changed in recent years,
information is scarce. The objective of the present study was to ascertain
whether the initial features of CML have changed over time, as well as the
possible impact on survival. DESIGN AND METHODS: The initial features of 167
patients diagnosed with chronic phase Ph-positive CML from 1972 to 1985 were
compared with those of 174 such patients diagnosed at the same institution from
1985 to 1998. The survival of the two groups was also compared. RESULTS: CML
patients diagnosed since 1985 were significantly older at presentation (mean age
47+17 vs 43+17 years, p = 0.04), were more often asymptomatic (36% vs 19%, p =
0.0003), less often had constitutional symptoms (30% vs 45%, p = 0.004), less
frequently had splenomegaly (59% vs 75%, p = 0.0008) and hepatomegaly (35% vs
49%, p = 0.01), had less marked leukocytosis (mean WBC count 139+/-124x10(9)/L vs
179+/-132x10(9)/L, p = 0.007), with 30% of them showing an initial WBC count
below 50x10(9)/L (vs 19%, p = 0.02), and showed less marrow blast cell
infiltration (p = 0.0003). No significant differences were observed in the
distribution by Sokal's risk groups. Median survival of patients diagnosed since
1985 was 5. 33 years (95% CI: 4.3-6.36), vs 4.06 years (95% CI: 3.28-4.84) for
patients diagnosed before (p = 0.07). Finally, patients asymptomatic at diagnosis
had a longer survival (median survival 5.7 years, 95% CI: 4.5-6.9, vs 4.1 years,
95% CI: 3.4-4.7, p = 0.03). INTERPRETATION AND CONCLUSIONS: A substantial
proportion of CML patients are currently diagnosed early in the course of the
disease. The effect of earlier diagnosis on survival prolongation in such
patients should be taken into account.
PMID- 10190945
TI - Fludarabine treatment in B-cell chronic lymphocytic leukemia: response, toxicity
and survival analysis in 47 cases.
AB - BACKGROUND AND OBJECTIVE: Fludarabine monophosphate (FAMP) is a purine analog
with specific therapeutic activity in B-cell chronic lymphocytic leukemia (CLL).
Its current use as front-line therapy of CLL is still a matter of debate both
because of the controversial results of the clinical trials so far reported and
because of the toxicity profile of the drug. In order to contribute to clarifying
the possible role of FAMP, we report a retrospective analysis of the results
obtained with the purine analog in CLL patients in different phases of the
disease. DESIGN AND METHODS: Forty-seven patients affected by advanced CLL, 36%
untreated, 31.9% relapsed and 31.9% resistant, were treated with FAMP 25
mg/m2/day, either for 4 days every 3 weeks in 29 cases, or for 5 days every 4
weeks in 18. The median number of FAMP cycles was 6 (range 2-11). Response was
defined according to total tumor mass (TTM) score reduction and toxicity was
expressed according to WHO grading criteria. The median follow-up of the series
was 13 months from the beginning of FAMP therapy. RESULTS: Out of 47 evaluable
patients the response rate was 74.4%, with 34% complete response (CR). The
overall response rate was 94%, 80% and 46.6% in untreated, relapsed and resistant
cases, respectively; a significantly higher number of responses was associated
with no previous treatment and number of FAMP cycles. Fifty-three percent of all
cases and 58.8% of untreated ones did not experience any toxicity. Treatment
related side effects were mainly autoimmune phenomena in untreated patients and
infectious complications in treated ones. One heavily pre-treated patient died
because of neurologic complications. Median time to re-treatment was18 months
(range 1-30) and was influenced by age and previous treatment. The overall median
survival was 35.7 months with a significantly higher proportion of surviving
cases among RAI 0-II stages, responders and patients receiving more than 5 FAMP
cycles. INTERPRETATION AND CONCLUSIONS: The present report confirms the high
efficacy of FAMP in previously pre-treated cases with acceptable toxicity and
encourages its use as front-line treatment provided that the results of
randomized trials demonstrate its superiority over conventional chemotherapy. The
possible development of autoimmune phenomena should, however, be considered
seriously.
PMID- 10190947
TI - Heteroduplex PCR analysis of rearranged immunoglobulin genes for clonality
assessment in multiple myeloma.
AB - BACKGROUND AND OBJECTIVE: Molecular analysis by PCR of monoclonally rearranged
immunoglobulin (Ig) genes can be used for diagnosis in B-cell lymphoproliferative
disorders (LPD), as well as for monitoring minimal residual disease (MRD) after
treatment. This technique has the risk of false-positive results due to the
"background" amplification of similar rearrangements derived from polyclonal B
cells. This problem can be resolved in advance by additional analyses that
discern between polyclonal and monoclonal PCR products, such as the heteroduplex
analysis. A second problem is that PCR frequently fails to amplify the junction
regions, mainly due to somatic mutations frequently present in mature (post
follicular) B-cell lymphoproliferations. The use of additional targets (e.g. Ig
light chain genes) can avoid this problem. DESIGN AND METHODS: We studied the
specificity of heteroduplex PCR analysis of several Ig junction regions to detect
monoclonal products in samples from 84 MM patients and 24 patients with B cell
polyclonal disorders. RESULTS: Using two distinct VH consensus primers (FR3 and
FR2) in combination with one JH primer, 79% of the MM displayed monoclonal
products. The percentage of positive cases was increased by amplification of the
Vlamda-Jlamda junction regions or kappa(de) rearrangements, using two or five
pairs of consensus primers, respectively. After including these targets in the
heteroduplex PCR analysis, 93% of MM cases displayed monoclonal products. None of
the polyclonal samples analyzed resulted in monoclonal products. Dilution
experiments showed that monoclonal rearrangements could be detected with a
sensitivity of at least 10(-2) in a background with >30% polyclonal B-cells, the
sensitivity increasing up to 10(-3) when the polyclonal background was <1% of
polyclonal B-cells. INTERPRETATION AND CONCLUSIONS: Heteroduplex analysis of PCR
amplified products is a simple and quick alternative for detecting monoclonally
rearranged Ig genes in MM. This can be applied for diagnosis of B cell LPD and as
a previous step in MRD strategies.
PMID- 10190948
TI - Plateau phase in multiple myeloma: an end-point of conventional-dose
chemotherapy.
AB - BACKGROUND AND OBJECTIVE: In multiple myeloma (MM) patients treated with
conventional chemotherapy, the attainment and duration of a plateau phase seems
to affect survival more than the degree of response to initial treatment. The
aims of this study are: 1) to analyze within a cohort of previously untreated MM
patients the incidence and the duration of the plateau phase; 2) to correlate it
with the presenting features; 3) to assess its impact on survival. DESIGN AND
METHODS: A series of 146 consecutive MM patients treated with conventional
chemotherapy were evaluated for this study. Of 146 patients, 102 responded (13
achieving complete response, 21 partial response, and 68 minimal response), and
44 showed less than minimal response or a progression. A plateau phase was
documented in 115 patients (comprising all responders and 13 non responders. The
median plateau phase duration was 21.6 months. The majority of patients received
intermittent cycles of chemotherapy (melphalan or interferon) during the plateau
phase. In multivariate analysis, lytic lesions, response, and time to the best
response (TBR) correlated with the attainment of a plateau, while stage, response
as a whole, and TBR showed a significant correlation with the duration. In
contrast, the type of response did not correlate with either the attainment or
the duration of plateau. To analyze the prognostic impact of presenting features,
response to therapy and plateau we used a hierarchical model for survival. The
analysis showed that the response to therapy and the duration of plateau
significantly affect the survival. INTERPRETATION AND CONCLUSIONS: In multiple
myeloma a plateau phase of at least 6 months' duration has a higher impact on
survival than the degree of response to conventional chemotherapy so plateau
duration could be used as target of therapeutic trials. The best way to maintain
the plateau phase remains, however, undefined.
PMID- 10190949
TI - Peripheral blood progenitor cell collections in cancer patients: analysis of
factors affecting the yields.
AB - BACKGROUND AND OBJECTIVE: Peripheral blood progenitor cells (PBPC) are now widely
used to restore hematopoiesis following high dose chemotherapy in patients with
malignancies. We sought to identify parameters that could predict the yield of
PBPC after mobilization with chemotherapy (CT) with or without granulocyte colony
stimulating factor (G-CSF) in cancer patients. DESIGN AND METHODS: One hundred
and fifty patients underwent 627 PBPC collections during the recovery phase
following CT with (n = 469) or without (n = 142) G-CSF. Hemogram, CFC-assays and
CD34+ cell count were performed on peripheral blood and leukaphereses products.
After log transformation of the data, differences between groups were assessed
with the unpaired t-test or one-way analysis of variance. RESULTS: Seventeen and
two patients required 2 and 3 mobilization cycles respectively to reach our
target of 15x10(4) CFU-GM/kg. In patients with lymphoma but not in those with
leukemia, the yields of both CFU-GM and CD34+ cells/kg were dramatically
increased when G-CSF was added to CT for mobilization. In collections primed with
CT and G-CSF, better yields were obtained in patients with breast cancer or small
cell lung carcinoma (SCLC) as opposed to other solid tumors and leukemia. Among
potential predictive factors of CT- and G-CSF-primed harvests, we found that the
CD34+ cell count in peripheral blood (PB) was strongly correlated with both the
CFU-GM and CD34+ cell yields. Except in leukemia patients, more than 1x10(6)
CD34+ cells/kg were harvested when the CD34+ cell count in blood was above
20x10(6)/L. Similarly, better results were obtained in collections performed when
the percentage of myeloid progenitors in blood on the day of apheresis was above
5 % or when the leukocyte count in blood was above 5x10(9)/L. INTERPRETATION AND
CONCLUSIONS: A diagnosis of breast cancer or SCLC, a leukocyte count in PB of
more than 5x10(9)/L, more than 5% myeloid progenitors or more than 20x10(6) CD34+
cells/L in PB were associated with higher yields of PBPC in collections mobilized
with CT+G-CSF.
PMID- 10190950
TI - Autologous stem cell transplantation in advanced follicular lymphoma. A single
center experience.
AB - BACKGROUND AND OBJECTIVE: The use of intensive therapy supported by autologous
stem cell transplantation (ASCT) is being investigated as treatment for poor
prognosis follicular lymphomas (FL). A single-center experience is herein
reported. DESIGN AND METHODS: From September 1990 to October 1997, 30 consecutive
patients (pts) with advanced FL received transplants, 8 of bone marrow and 22 of
peripheral blood. Thirteen harvests were purged by an immunomagnetic method using
anti-B antibodies. Twenty-seven patients received salvage chemotherapy (CT)
before ASCT with the objective of reaching this procedure in the best possible
response. The disease status at ASCT was: 1(st) CR in 7 pts, > or =2(nd) CR in 6
pts, PR in 10 pts, untreated relapse in 2 pts and chemoresistant disease in 5
pts. RESULTS: There was only one transplant-related death (one month after ASTC).
With a median follow-up of 19 (1-89) months, 27 pts are alive, 8 pts have
relapsed/progressed at a median time of 11 (6-22) months after ASCT. The
estimated 2-year PFS and OS are 57% (95% CI, 34-81%) and 83% (95% CI, 64-100%).
When comparing the progression-free interval (PFI) before salvage CT and ASCT and
the PFI after ASCT, of 17 evaluable pts, 10 had a PFI after ASCT longer than the
previous interval, and 5 additional pts remain in CR/PR with a follow-up that has
not yet reached the duration of pre-transplant response. By contrast, 2 pts had a
short post-transplant response. INTERPRETATION AND CONCLUSIONS: High-dose therapy
followed by ASCT obtains a high rate of responses, frequently longer than any
previous PFI. Additional follow-up is necessary to determine whether there is any
"plateau" in response duration and to define what proportion of pts may be cured
with ASCT in this setting.
PMID- 10190951
TI - The prothrombin gene variant 20210A in venous and arterial thromboembolism.
AB - Several hereditary disorders affecting coagulation factors have been identified
as prothrombotic risk factors. Recently, the prothrombin 20210 A/G mutation has
been identified as a second important polymorphism involved in venous thrombosis.
This article reviews all published information about this new procoagulant
mutation. Our group has been involved in a number of studies about the role and
importance of polymorphisms in thromboembolic disease, including the analysis of
the prothrombin 20210 A/G mutation. Moreover, an extensive Medline literature
search was made to complete the review using the key words: prothrombin mutation,
20210, venous or arterial thrombosis. The combination of environmental and
genetic risk factors determines the relative risk that any individual has of
suffering a thrombotic episode. Some genetic mutations affecting coagulation
factors have been described. Recently, Poort et al. described a new mutation in
the 3'-untranslated region of the prothrombin gene. The prothrombin 20210 G/A
mutation, associated with elevated levels of factor II in plasma, significantly
increases the risk of developing venous thrombosis. In fact, this polymorphism is
the second most important genetic risk factor for venous thrombosis in Caucasian
populations. Moreover, and supporting the multifactorial feature of
thromboembolic diseases, this mutation greatly increases the possibility of
developing a thrombotic episode when combined with other environmental or genetic
risk factors. The role of this procoagulant mutation in arterial vascular disease
is, however, unclear.
PMID- 10190952
TI - Regulation and functions of the protein C anticoagulant pathway.
AB - The protein C pathway plays a critical role in the negative regulation of the
blood clotting process. We recently identified an endothelial cell receptor for
protein C/activated protein C (APC). The receptor is localized almost exclusively
on endothelial cells of large vessels and is present at only trace levels or
indeed absent from capillaries in most tissues. Patients with sepsis or lupus
erythematosus exhibit elevated levels of plasma EPCR which migrates on gels as a
single band and is fully capable of binding protein C/APC. There is no
correlation with thrombomodulin levels, probably due to different vascular
localizations and/or cellular release mechanisms. To understand the mechanisms by
which EPCR plasma levels are elevated, we examined EPCR mRNA expression in a rat
endotoxin shock model. The EPCR mRNA gene exhibited an early immediate gene
response to endotoxin with the mRNA levels increasing nearly 4 fold in the first
3-6 hrs, before returning toward baseline. Plasma levels of EPCR also rose about
4 fold with little change in tissue EPCR levels. Both processes were markedly
attenuated by hirudin suggesting that thrombin was responsible for increases in
mRNA and plasma EPCR levels. At the level of mRNA, the induction is mediated by a
thrombin response element in the 5' flanking region of the gene. Direct thrombin
infusion and cell culture experiments support this contention. On endothelium,
thrombin is capable of releasing cell surface EPCR and this process is blocked by
the metalloproteinase inhibitor orthophenanthroline. Taken together these studies
indicate that elevation in soluble plasma EPCR reflects endothelial cell
activation in the larger vessels and is likely to be an indication of local
thrombin generation near these vessel surfaces.
PMID- 10190954
TI - Heinz bodies interfere with automated reticulocyte counts.
PMID- 10190953
TI - New reciprocal translocation t(5;10)(q33;q22) associated with atypical chronic
myeloid leukemia.
AB - We report a new chromosomal reciprocal translocation t(5;10)(q33;q22) in a 49
year-old man with atypical chronic myeloid leukemia (a-CML) and history of
occupational exposure to petroleum products including benzene and other
hydrocarbons. The t(5;10) (q33;q22) was found in 94% and 84% of metaphases in
peripheral blood and bone marrow cells, respectively. Cytogenetic analysis of
single colonies derived from granulocyte-macrophage (CFU-GM), and erythroid (BFU
E) hematopoietic progenitors showed that 88% and 40% of CFU-GM and BFU-E,
respectively, had the t(5;10)(q33;q22). In contrast, peripheral blood T
lymphocytes, and cutaneous fibroblasts had normal 46,XY karyotype. Molecular
analysis of the t(5;10)(q33;q22) translocation breakpoint is currently underway
in order to identify genes located in this region which might provide insights
into the pathogenesis of atypical myeloproliferative disorders.
PMID- 10190955
TI - Splenic mucormycosis.
PMID- 10190956
TI - Hematologic response in type I Gaucher's disease after enzyme replacement
therapy.
PMID- 10190957
TI - p53 overexpression in refractory anemia. An immunohistochemical analysis of bone
marrow biopsies.
PMID- 10190958
TI - A complex immunodeficiency. Idiopathic CD4+ T-lymphocytopenia and
hypogammaglobulinemia associated with HHV8 infection, Kaposi's sarcoma and
gastric cancer.
PMID- 10190959
TI - Molecular analysis of granulocytic sarcoma: a single center experience.
PMID- 10190960
TI - A rapid prenatal diagnosis of hemophilia A by DNA analysis on crude chorionic
villus biopsy.
PMID- 10190961
TI - Burkitt's lymphomas in adults: retrospective analysis of 30 cases treated with
two different schemes.
PMID- 10190962
TI - Erythropoietin and iron therapy for preterm infants.
PMID- 10190964
TI - Reply.
PMID- 10190963
TI - Reply.
PMID- 10190965
TI - Welcome to never-neverland.
PMID- 10190966
TI - Reply.
PMID- 10190967
TI - Modifications of Ca2+ mobilization and noradrenaline release by S-nitroso
cysteine in PC12 cells.
AB - The effects of nitrogen monoxide (NO)-related compounds on cytosolic free Ca2+
concentrations ([Ca2+]i) and noradrenaline (NA) release in neurosecretory PC12
cells were investigated. The addition of S-nitroso-cysteine (SNC) stimulated
[Ca2+]i increases from an intracellular Ca2+ pool continuously in a concentration
dependent manner. Other NO donors, which stimulate cyclic GMP accumulation, did
not cause [Ca2+]i increases. After treatment with 0.2 mM SNC, transient increases
in [Ca2+]i from the Ca2+ pool induced by caffeine were completely abolished. The
addition of N-ethylmaleimide (NEM) caused sustained [Ca2+]i increases from the
intracellular Ca2+ pool. Furthermore, caffeine did not stimulate further [Ca2+]i
increases in PC12 cells pretreated with NEM. These findings suggest that SNC and
NEM predominantly interact with a caffeine-sensitive Ca2+ pool. The addition of
dithiothreitol (DTT) to 0.4 mM SNC-stimulated cells reduced [Ca2+]i to basal
levels, and the addition of DTT to NEM-stimulated cells locked [Ca2+]i at high
levels. The stimulatory effects of SNC but not NEM were not abolished by
pretreatment with DTT. These findings suggest that modification of the oxidation
status of the sulfhydryl groups on the caffeine-sensitive receptors by SNC or NEM
regulates Ca2+ channel activity in a reversible manner. SNC did not stimulate NA
release by itself but did inhibit ionomycin-stimulated NA release. In contrast,
NEM stimulated NA release in the absence of extracellular CaCl2 and further
enhanced ionomycin-stimulated NA release. Ca2+ mobilization by SNC from the
caffeine-sensitive pool was not a sufficient factor, and other factors
stimulating NA release may be negatively regulated by SNC.
PMID- 10190968
TI - Small intestinal UDP-glucuronosyltransferase sheUGT1A07: partial purification and
cDNA cloning from sheep small intestine.
AB - A phenol UDPglucuronosyltransferase (UGT) was partially purified, and the cDNA
encoding the isoform was cloned and sequenced from sheep small intestine. The
purified preparation containing a one major band (57 kDa) and one minor band (50
kDa) revealed high activities toward xenobiotics such as 1-naphthol (1-NA), 4
nitrophenol, and 4-methylumbelliferone. The preparation, however, had only little
activity toward 4-hydroxybiphenyl and no activity toward bilirubin, suggesting
that the preparation contains UGT1 isoforms. The NH2-terminal amino acid sequence
of the major band was determined to be Gly-Lys-Leu-Leu-Val-Val-Pro-Met-Asp-Gly
Ser. A full-length UGT cDNA was obtained by reverse transcription-polymerase
chain reaction with the degenerated 5'-primer from the NH2-terminal amino acid
sequence of the purified major one and rapid amplification of cDNA ends from
sheep small intestine. The cloned cDNA named sheUGT1A07 by amino acid similarity
has a NH2-terminus sequence identical to that of the purified major one. Another
phenol UGT cDNA named sheUGT1A6 was also cloned from sheep liver. sheUGT1A6 was
expressed mainly in the liver, whereas sheUGT1A07 mRNA was expressed almost only
in the alimentary organs, suggesting that sheUGT1A6 plays a role as a general
drug metabolizing UGT isoform in the liver and sheUGT1A07 plays important role in
the xenobiotics glucuronidation in the sheep small intestine.
PMID- 10190969
TI - In vivo prenylation of rat proteins: modification of proteins with penta- and
hexaprenyl groups.
AB - In vivo protein prenylation was studied in newborn rats by repeated injections of
[3H]mevalonate. The highest level of protein-bound mevalonate metabolites was
found in the kidney, but incorporation was observed in all organs studied. After
fluorography of SDS-polyacrylamide gel electrophoresis-separated polypeptides,
labeling was found in the 21- to 28-kDa molecular mass region and, after
prolonged exposure of the film, additional bands at both higher and lower
molecular masses could be detected. Protein prenylation in the kidney increased
during the first 5 days after birth, whereas that in the liver reached a maximum
on the fourth day. After methyliodide treatment of the prenylated proteins,
farnesol, geranylgeraniol, and two larger isoprenoids, pentaprenol and
hexaprenol, were released. In the liver, the ratio of protein-bound
geranylgeraniol to farnesol increased from 2 to 4.5 during the first 5 days after
birth. Upon subfractionation of the kidney, the highest level of labeling was
found in mitochondria and microsomes. When the mitochondria were subfractionated
into outer membranes, intermembrane space and an inner membrane/matrix fraction,
the labeling pattern of prenylated polypeptides differed in all fractions. The
results demonstrate that in vivo labeling of rats can be performed to study the
extent, type, and distribution of protein prenylation.
PMID- 10190970
TI - Interaction of Nickel(II) with histones: in vitro binding of nickel(II) to the
core histone tetramer.
AB - The absorption spectra of Ni(II) bound to the core histone tetramer, (H3-H4)2, of
chicken erythrocytes in 500 mM NaCl + 100 mM phosphate (pH 7.4) were recorded. A
charge transfer band was seen at 317 nm, characteristic of a bond between Ni(II)
and the sulfur atom of Cys-110 of histone H3. The conditional affinity constants
for Ni(II) binding at pH 7.4 for low and high Ni(II) saturation (log Kc = 4.26 +/
0.02 and 5.26 +/- 0.11 M-1, respectively) were calculated from
spectrophotometric titrations with the use of this band. The binding of Ni(II) to
(H3-H4)2 is proposed to involve the Cys-110 and His-113 of different H3 molecules
within the tetramer. The competition between histones and low-molecular-weight
chelators for Ni(II) in the cell nucleus, histidine and glutathione, is discussed
on the basis of the above results, indicating that histone H3 is very likely to
bind Ni(II) dissolved intracellularly from phagocytosed particulate nickel
compounds.
PMID- 10190971
TI - Isolation, characterization, and mechanistic studies of (-)-alpha-gurjunene
synthase from Solidago canadensis.
AB - The leaves of the composite Solidago canadensis (goldenrod) were shown to contain
(-)-alpha-gurjunene synthase activity. This sesquiterpene is likely to be the
precursor for cyclocolorenone, a sesquiterpene ketone present in high amounts in
S. canadensis leaves. (-)-alpha-Gurjunene synthase was purified to apparent
homogeneity (741-fold) by anion-exchange chromatography (on several matrices),
dye ligand chromatography, hydroxylapatite chromatography, and gel filtration.
Chromatography on a gel filtration matrix indicated a native molecular mass of 48
kDa, and SDS-PAGE showed the enzyme to be composed of one subunit with a
denatured mass of 60 kDa. Its maximum activity was observed at pH 7.8 in the
presence of 10 mM Mg2+ and the KM value for the substrate farnesyl diphosphate
was 5.5 microM. Over a range of purification steps (-)-alpha-gurjunene and (+)
gamma-gurjunene synthase activities copurified. In addition, the product ratio of
the enzyme activity under several different assay conditions was always 91% (-)
alpha-gurjunene and 9% (+)-gamma-gurjunene. This suggests that the formation of
these two structurally related products is catalyzed by one enzyme. For further
confirmation, we carried out a number of mechanistic studies with (-)-alpha
gurjunene synthase, in which an enzyme preparation was incubated with deuterated
substrate analogues. Based on mass spectrometry analysis of the products formed,
a cyclization mechanism was postulated which makes it plausible that the synthase
catalyzes the formation of both sesquiterpenes.
PMID- 10190972
TI - Glycolytic metabolites and intracellular signaling in the pancreatic beta cell.
AB - In the pathways modulating the secretion of insulin and other physiologically
important molecules, the critical role played by calcium in the moment-to-moment
regulation of secretory processes may be modulated by additional factors, and
these factors may include the glycolytic metabolites. We studied these early
glucose breakdown products for effects on calcium release and inositol 1,4, 5
trisphosphate (IP3) binding to the IP3 receptor in a pancreatic beta cell
preparation. The physiological significance of the response was also examined in
terms of the insulinotropic effects of these metabolites. In studies of calcium
release from the pancreatic beta cell, the metabolite 2,3-bisphosphoglycerate
(DPG) exerted a statistically significant stimulatory effect on calcium release.
A lesser but nonetheless significant effect also occurred in the presence of 3
phosphoglycerate and glucose-6-phosphate. The DPG-induced effect was
concentration dependent. It is likely that the effects of DPG and other
glycolytic metabolites on pancreatic beta cell signaling are physiologically
significant inasmuch as we were also able to demonstrate that DPG and other
glycolytic metabolites promoted the release of insulin from the pancreatic beta
cell.
PMID- 10190973
TI - Ability of cytosolic malate dehydrogenase and lactate dehydrogenase to increase
the ratio of NADPH to NADH oxidation by cytosolic glycerol-3-phosphate
dehydrogenase.
AB - At the normal pH of the cytosol (7.0 to 7.1) and in the presence of physiological
(1.0 mM) levels of free Mg2+, the Vmax of the NADPH oxidation is only slightly
lower than the Vmax of NADH oxidation in the cytosolic glycerol-3-phosphate
dehydrogenase (E.C. 1.1.1.8) reaction. Under these conditions physiological (30
microM) levels of cytosolic malate dehydrogenase (E.C. 1.1.1.37) inhibited
oxidation of 20 microM NADH but had no effect on oxidation of 20 microM NADPH by
glycerol-3-phosphate dehydrogenase. Consequently malate dehydrogenase increased
the ratio of NADPH to NADH oxidation of glycerol-3-phosphate dehydrogenase. On
the basis of the measured KD of complexes between malate dehydrogenase and these
reduced pyridine nucleotides, and their Km in the glycerol-3-phosphate
dehydrogenase reactions, it could be concluded that malate dehydrogenase would
have markedly inhibited NADPH oxidation and inhibited NADH oxidation considerably
more than observed if its only effect were to decrease the level of free NADH or
NADPH. This indicates that due to the opposite chiral specificity of the two
enzymes with respect to reduced pyridine nucleotides, complexes between malate
dehydrogenase and NADH or NADPH can function as substrates for glycerol-3
phosphate dehydrogenase, but the complex with NADH is less active than free NADH,
while the complex with NADPH is as active as free NADPH. Mg2+ enhanced the
interactions between malate dehydrogenase and glycerol-3-phosphate dehydrogenase
described above. Lactate dehydrogenase (E.C. 1.1.1.27) had effects similar to
those of malate dehydrogenase only in the presence of Mg2+. In the absence of
Mg2+, there was no evidence of interaction between lactate dehydrogenase and
glycerol-3-phosphate dehydrogenase.
PMID- 10190974
TI - Conformational alteration in serum albumin as a carrier for pyridoxal phosphate:
a distinction from pyridoxal phosphate-dependent glutamate decarboxylase.
AB - The conformation of bovine serum albumin (BSA), a pyridoxal phosphate (pyridoxal
P) carrier, was investigated by using uv/visible spectrophotometry, fluorescence
spectroscopy, circular dichroism, and differential scanning microcalorimetry.
Upon interacting with pyridoxal-P, the uv/visible absorption spectrum of BSA
exhibits peaks at 330 and 392 nm due to the formation of a Schiff base. Pyridoxal
P quenches the fluorescence emission intensity (excited at 295 or 280 nm) by 24%
and enhances fluorescence steady-state polarization of BSA by 20%. These
observations suggest a conformational change in BSA when it interacts with
pyridoxal-P. However, this conformational change appears to be small since
circular dichroism showed only a 2-4% decrease in the alpha-helical content of
BSA and no change in the beta-sheet content, and differential scanning
microcalorimetry yielded only a 10% change in the enthalpy of thermal unfolding
of BSA. 2-Aminoethylisothiouronium bromide, an antioxidant, causes no effect on
either uv/visible absorption spectrum or fluorescence emission intensity of BSA,
suggesting that BSA lacks sensitive sulfhydryl groups. To help in understanding
BSA as a carrier for pyridoxal-P, the results were compared with those for
glutamate decarboxylase (GAD), a pyridoxal-P-dependent protein, which requires
pyridoxal-P as the cofactor for activity. Although BSA and GAD exhibit comparable
molecular weights (66430 versus 65300), numbers of amino acid residues (582
versus 585), and binding affinity (>10(6) M-1), distinct conformational
alterations occur between the two proteins upon interacting with pyridoxal-P: a
small conformational change for BSA versus a large conformational change for GAD.
In contrast to the case of BSA, AET causes significant effects on both the
uv/visible spectrum and fluorescence emission intensity of GAD, because GAD
contains sensitive sulfhydryl groups. Factors such as disulfide bond and active
site sequence were discussed to understand BAS as a carrier for pyridoxal-P and a
pyridoxal-P-independent protein.
PMID- 10190975
TI - Involvement of farnesyl protein transferase (FPTase) in FcarepsilonRI-induced
activation of RBL-2H3 mast cells.
AB - Changes in farnesyl protein transferase (FPTase) activity and FPTase beta-subunit
protein levels were determined in IgE-sensitized RBL-2H3 mast cells in response
to polyvalent antigen administration. Ten minutes after the addition of DNP
modified BSA to mast cells, whose high affinity receptor for IgE (FcvarepsilonRI)
contained bound anti-DNP IgE, FPTase specific activity increased by 54 +/- 28%.
Time course studies showed FPTase specific activity doubled during a 20- to 30
min period after antigen-induced cell aggregation. Also, an increase in FPTase
beta-subunit protein during this time ( approximately 30%) was observed; this
protein increase was not accompanied by a similar increase in FPTase beta-subunit
m-RNA levels. The FcvarepsilonRI aggregation had no significant effect on the
activities of other enzymes involved with farnesyl diphosphate (FPP) metabolism:
FPP synthase, isopentenyl diphosphate isomerase, geranylgeranyl protein
transferase, and squalene synthase. Specific inhibition of FPTase activity by
manumycin was studied to determine what role FPTase plays in mast cell
activation. Manumycin profoundly inhibited hexosaminidase release in activated
cells, indicating FPTase is required for signal transduction involved with
protein exocytosis from RBL-2H3 mast cells.
PMID- 10190976
TI - Do damaged proteins accumulate in Caenorhabditis elegans L-isoaspartate
methyltransferase (pcm-1) deletion mutants?
AB - The protein l-isoaspartate (d-aspartate) O-methyltransferase (E.C. 2. 1.1.77) can
initiate the conversion of isomerized and racemized aspartyl residues to their
normal l-aspartyl forms and has therefore been hypothesized to function as a
repair enzyme, responsible for helping to limit the accumulation of damaged
proteins in aging organisms. In this study, the effect of a disruption in the pcm
1 gene encoding the l-isoaspartyl methyltransferase was investigated in the
nematode Caenorhabditis elegans. It was found that damaged proteins recognized by
this enzyme accumulated to significant levels during long-term incubation of both
pcm-1+ and pcm-1- nematodes in a specialized larval stage called the dauer. The l
isoaspartyl methyltransferase-deficient mutants accumulated about twice the level
of damaged proteins as the control nematodes during dauer aging. The mutants also
accumulated higher levels of damage when both strains were incubated at 30
degrees C for up to 3 days. However, when nonviable nematodes were removed in a
Percoll separation, similar levels of damage were measured between the two
strains following both dauer aging and 30 degrees C incubation. Both strains were
able to effectively eliminate damaged proteins recognized by the
methyltransferase after recovery from dauer. Characterization of the methyl
accepting polypeptide substrates which accumulate in aged dauers revealed that
although substrates of all molecular weights are present, the majority of
substrates are peptides not precipitated by acetone. These results suggest that
protein degradation, rather than repair, may be the major mechanism by which C.
elegans eliminates damaged proteins containing l-isoaspartyl residues.
PMID- 10190977
TI - Engineered glycolytic glyceraldehyde-3-phosphate dehydrogenase binds the anti
conformation of NAD+ nicotinamide but does not experience A-specific hydride
transfer.
AB - Glycolytic glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a NAD-dependent
oxidoreductase which catalyzes the oxidative phosphorylation of d-glyceraldehyde
3-phosphate (G3P) to form 1, 3-diphosphoglycerate. The currently accepted
mechanism involves an oxidoreduction step followed by a phosphorylation. GAPDH is
classified as a B-specific oxidoreductase. The inspection of several crystal
structures of GAPDHs indicates that the efficient hydride transfer from the
hemithioacetal intermediate to the C4 position of the pyridinium si face requires
optimal nicotinamidium-protein contacts for a suitable pyridinium-ring
orientation. In previous studies carried out on Escherichia coli GAPDH (C.
Corbier, A. Mougin, Y. Mely, H. W. Adolph, M. Zeppezauer, D. Gerard, A. Wonacott,
and G. Branlant, Biochimie 72, 545-554, 1990; J. Eyschen, C. Corbier, B. Vitoux,
G. Branlant, and M. T. Cung, Protein Pept. Lett. 1, 19-24, 1994), the role of the
invariant Asn 313 residue, as an anchor which favors the syn orientation of the
nicotinamide ring, was examined. Here, we report further investigations on the
molecular factors responsible for the cofactor stereospecificity. Two single
[Gly317] and [Ala317] GAPDH mutants and one double [Thr313-Gly317] GAPDH mutant
were constructed on the basis of a molecular modelling study from the crystal
structure of holo GAPDH from E. coli (E. Duee, L. Olivier-Deyris, E. Fanchon, C.
Corbier, G. Branlant, and O. Dideberg, J. Mol. Biol. 257, 814-838, 1996). The Kd
constants of [Ala317], [Gly317], and [Thr313-Gly317] GAPDH mutants for NAD are 5,
13, and 300 times higher than that of wild-type GAPDH. Transferred nuclear
Overhauser effect spectroscopy demonstrates that the wild-type syn orientation of
bound nicotinamide remains unchanged in the [Gly317] and [Ala317] mutants,
whereas a conformational equilibrium between the syn and anti forms occurs in the
[Thr313-Gly317] double mutant with a preference for the anti conformer. Although
the double mutant preferably binds the nicotinamide ring in an anti conformation,
it still exhibits B hydride transfer stereospecificity. Yet, the catalytic
efficiency is much less than that of the wild type. This indicates that the holo
GAPDH mutant fraction with an anti orientation of bound NAD is not capable of
forming the ternary complex with G3P which would be required for an efficient A
specific catalytic process. The reasons of this catalytic inefficiency are
discussed in relation with the historical and functional models which were
advanced to explain the stereospecificity of NAD(P)-dependent dehydrogenases.
PMID- 10190978
TI - Regulation of glutamine synthetase from the white button mushroom Agaricus
bisporus.
AB - The regulation of glutamine synthetase (GS) from Agaricus bisporus was studied at
the posttranscriptional level using a specific antibody fraction directed against
purified GS. The cross-reactivity of the antiserum against various Agaricus
species and other fungi was tested and low reactivity with the Ascomycetes was
found. GS protein and activity levels were measured in cell-free extracts of
mycelium grown on different N sources. In mycelium grown on glutamine or ammonium
as N source, the biosynthetic GS activity is higher than the transferase
activity. Moreover, the results show a correlation between GS biosynthetic
activity, GS protein, and previously reported mRNA levels. Also, after addition
of ammonium or glutamine to glutamate-utilizing cultures, transferase activity
decreased more rapidly than biosynthetic activity and GS protein level. This
suggests a conformational modification which only affects transferase activity.
PMID- 10190979
TI - A specific inhibitor of heart cytosolic 5'-nucleotidase I attenuates hydrolysis
of adenosine 5'-monophosphate in primary rat myocytes.
AB - ATP breakdown was triggered in primary rat myocytes in the presence of coformycin
to force the catabolism of AMP through hydrolysis to adenosine. Selective
inhibitors of the cytosolic 5'-nucleotidase I (c-N-I) from myocardium were used
to measure the intracellular contribution of this enzyme to AMP hydrolysis under
these conditions. The selective inhibitor 5-ethynyl-2',3'-dideoxyuridine
inhibited the hydrolysis of AMP to adenosine in a concentration-dependent manner
with an IC50 value of 20 microM. Maximal inhibition prevented 76% of the
conversion of AMP to adenosine, indicating that under these conditions the
majority of AMP hydrolysis in rat myocytes occurs through this enzyme. When ATP
breakdown was triggered in the presence of thymidine 5'-phosphonate, a more
potent inhibitor of the purified cytosolic 5'-nucleotidase, less inhibition of
AMP hydrolysis occurred and only after prolonged preincubation of the myocytes
with the inhibitor. These data demonstrate that the selective nucleoside
inhibitors of c-N-I can effectively block the hydrolysis of AMP inside myocytes.
Thus, these inhibitors may be useful tools in identifying the role of c-N-I
during ATP catabolism in whole tissue and animal experiments.
PMID- 10190980
TI - Transcription factor AP-2 mRNA and DNA binding activity are constitutively
expressed in SV40-immortalized but not normal human lung fibroblasts.
AB - Large T antigen (LT) expressed by the oncogenic DNA virus SV40 transforms cells
by interacting with and perturbing the normal function of several important
cellular proteins including P53, RB, c-MYC, and AP-2. AP-2 binds to regulatory
elements within the SV40 enhancer and is therefore of particular interest for
mechanisms relating to viral transcription, replication, and packaging. LT
antigen has been previously shown to inhibit transcription factor AP-2 from
binding to its cognate cis-element in DNA in vitro, and this is believed to occur
through a direct physical interaction between the LT and AP-2 proteins. Recently
LT and AP-2 were shown to interact at the protein level in vivo and this
interaction appeared to mediated by the RB protein. Although LT inhibited AP-2
DNA binding in vitro, the effects of LT on AP-2 expression and DNA binding
activity in vivo have not been previously reported. We report here that
transcription factor AP-2alpha is constitutively expressed in SV40-transformed
cells compared to their normal cell counterparts. The overexpression of AP-2alpha
in SV40 transformed cells occurred at the levels of mRNA, protein, and DNA
binding activity. The increase in AP-2 DNA binding in vivo was particularly
interesting since previous studies in vitro would have predicted that AP-2 DNA
binding should be decreased in the presence of LT. AP-2 is a plieotropic
regulator of gene expression, activating some and repressing others. Thus,
increased cellular AP-2 activity may be an important downstream effector for the
transforming ability of SV40.
PMID- 10190981
TI - Human epidermal keratinocytes upregulate expression of the prolactin receptor
after the onset of terminal differentiation, but do not respond to prolactin.
AB - Growing and differentiating keratinocytes maintain the epidermal barrier. This is
partly controlled by growth factors and hormones. Prolactin (PRL) is named after
its hormonal role in mammals during lactation, but is found in all vertebrates
where PRL exerts various effects. In serum-free keratinocyte cultures, PRL was
thought to be the factor responsible for the proliferative effect of bovine
pituitary extract. Here, we evaluated PRL as a clonogenic factor for
keratinocytes and found no mitogenic activity. Studying the expression of the PRL
receptor by keratinocytes, we found the receptor upregulated only after culture
confluence, in differentiating keratinocytes, but we were unable to detect any
cellular response to PRL. The hormone does not alter the gene expression of
either early (suprabasal keratin) or late (involucrin) differentiation markers by
keratinocytes. Accordingly, no activation of the transcription factor Stat5 by
PRL can be detected in keratinocytes, Stat5 being nevertheless detected by
Western blot.
PMID- 10190982
TI - Functional role of oxygen-containing residues in the fifth transmembrane segment
of the Na,K-ATPase alpha subunit.
AB - The functional roles of Tyr771, Thr772, and Asn776 in the fifth transmembrane
segment of the Na, K-ATPase alpha subunit were studied using site-directed
mutagenesis, expression, and kinetics analysis. Nonconservative replacements
Thr772Tyr and Asn776Ala led to reduced Na,K-ATPase turnover. Replacements at
these positions (Asn776Ala, Thr772Leu, and Thr772Tyr) also led to high Na-ATPase
activity (in the absence of K+). However, Thr772- and Asn776-substituted enzymes
showed only small alterations in the apparent Na+ and K+ affinities (K1/2 for
Na,K-ATPase activation). Thus, the high Na-ATPase activity does not appear
related to cation-binding alterations. It is probably associated with
conformational alterations which lead to an acceleration of enzyme
dephosphorylation by Na+ acting at the extracellular space (Arguello et al. J.
Biol. Chem. 271, 24610-24616, 1996). Nonconservative substitutions at position
771 (Tyr771Ala and Tyr771Ser) produced a significant decrease of enzyme turnover.
Enzyme-Na+ interaction was greatly changed in these enzymes, while their
activation by K+ did not appear affected. Although the Na+ K1/2 for Na,K-ATPase
stimulation was unchanged (Tyr771Ala, Tyr771Ser), the activation by this cation
showed no cooperativity (Tyr771Ala, nHill = 0.75; Tyr771Ser, nHill = 0.92;
Control, nHill = 2.28). Substitution Tyr771Phe did not lead to a significant
reduction in the cooperativity of the ATPase Na+ dependence (nHill = 1.91). All
Tyr771-substituted enzymes showed low steady-state levels of phosphoenzyme during
Na-activated phosphorylation by ATP. Phosphorylation levels were not increased by
oligomycin, although the drug bound and inactivated Tyr771-substituted enzymes.
No E1 left and right arrow E2 equilibrium alterations were detected using
inhibition by vanadate as a probe. The data suggest that Tyr771 might play a
central role in Na+ binding and occlusion without participating in K+-enzyme
interactions.
PMID- 10190983
TI - Molecular cloning of retinal oxidase/aldehyde oxidase cDNAs from rabbit and mouse
livers and functional expression of recombinant mouse retinal oxidase cDNA in
Escherichia coli.
AB - Retinal oxidase (EC 1.2.3.11) is a molybdenum-containing flavoenzyme with high
enzymatic activity as to retinoic acid synthesis. In this study, we provide
direct evidence that retinal oxidase is identical to aldehyde oxidase (EC
1.2.3.1) by cDNA cloning. Retinal oxidase and aldehyde oxidase, purified from
rabbit liver cytosol using the original methods, showed completely identical HPLC
patterns and amino acid sequences for three corresponding polypeptides (103 amino
residues). The primary structural information obtained from the cleaved
polypeptides permitted molecular cloning of the full-length cDNA of rabbit liver
retinal oxidase (aldehyde oxidase). We also cloned and sequenced the full-length
cDNA of mouse retinal oxidase. The cDNAs of rabbit and mouse retinal oxidase have
a common sequence approximately 4.6 kb long, comprising 4-kb coding regions. The
open reading frames of the cDNAs predict single polypeptides of 1334 and 1333
amino acids; the calculated minimum molecular mass of each is approximately
147,000. Northern blot analysis showed that the rabbit retinal oxidase mRNA was
widely expressed in tissues. Finally, we successfully constructed a prokaryotic
expression system for mouse retinal oxidase. The purified recombinant retinal
oxidase from Escherichia coli showed a typical spectrum of aldehyde oxidases and
a lower Km (3.8 microM) for retinal and a higher Vmax (807 nmol/min/mg protein)
for retinoic acid synthesis than those of rabbit retinal oxidase (8 microM and
496 nmol/min/mg protein). This represents the first eukaryotic molybdenum
containing flavoprotein to be expressed in an active form in a prokaryotic
system.
PMID- 10190984
TI - Partial purification and characterization of acetyl coenzyme A: taxa-4(20),11(12)
dien-5alpha-ol O-acetyl transferase that catalyzes the first acylation step of
taxol biosynthesis.
AB - The acetylation of taxa-4(20),11(12)-dien-5alpha-ol is considered to be the third
specific step of Taxol biosynthesis that precedes further hydroxylation of the
taxane nucleus. An operationally soluble acetyl CoA:taxadienol-O-acetyl
transferase was demonstrated in extracts of Taxus canadensis and Taxus cuspidata
cells induced with methyl jasmonate to produce Taxol. The reaction was dependent
on both cosubstrates and active enzyme, and the product of this acetyl
transferase was identified by radiochromatographic and GC-MS analysis. Following
determination of the time course of acetyl transferase appearance in induced cell
cultures, the operationally soluble enzyme was partially purified by a
combination of anion exchange, hydrophobic interaction, and affinity
chromatography on immobilized coenzyme A resin. This acetyl transferase has a pI
and pH optimum of 4.7 and 9.0, respectively, and a molecular weight of about
50,000 as determined by gel permeation chromatography. The enzyme shows high
selectivity and high affinity for both cosubstrates, with Km values of 4.2 and
5.5 microM for taxadienol and acetyl CoA, respectively. The enzyme does not
acetylate the more advanced Taxol precursors, 10-deacetylbaccatin III or baccatin
III. This acetyl transferase is insensitive to monovalent and divalent metal
ions, is only weakly inhibited by p-hydroxymercuribenzoate, N-ethylmaleimide, and
coenzyme A, and resembles in general properties the few other O-acetyl
transferases of higher plant origin that have been examined.
PMID- 10190985
TI - Characterization of P1,P4-diadenosine 5'-tetraphosphate binding on bovine aortic
endothelial cells.
AB - In recent years it has become increasingly clear that alpha, omega-dinucleotides
act as extracellular modulators of various biological processes. P1,P4
diadenosine 5'-tetraphosphate (Ap4A) is the best characterized alpha,omega
dinucleotides and acts as an extracellular signal molecule by inducing the
release of nitric oxide (NO) from bovine aortic endothelial cells (BAEC) (R. H.
Hilderman, and E. F. Christensen (1998) FEBS Lett. 407, 320-324). However, the
characteristics of Ap4A binding to endothelial cells have not been determined. In
this report we demonstrate that Ap4A binds to a heterogeneous population of
receptors on BAEC. Competition ligand-binding studies using various adenosine
dinucleotides, guanosine dinucleotides, adenosine/guanosine dinucleotides, and
synthetic P2 purinoceptor agonists and antagonists demonstrate that Ap4A binds to
a receptor on BAEC that has a high affinity for some of the adenosine
dinucleotides. The apparent IC50 values for Ap4A, Ap2A, and Ap3A are between 12
and 15 microM, while the apparent IC50 values for Ap5A and Ap6A are greater than
500 microM. Evidence is also presented which suggests that this receptor can be
classified as a putative P4 purinoceptor. Competition studies also demonstrate
that Ap4A binds at a lower affinity to a second class of binding sites.
PMID- 10190986
TI - Isolation of human salivary mucin MG2 by a novel method and characterization of
its interactions with oral bacteria.
AB - Human salivary mucin MG2 was purified from submandibular/sublingual gland
secretion by ultrafiltration and sequential gel filtration chromatography on
Sephadex G-200, Superose 6 (prepgrade), and Superose 6. This method differs from
earlier procedures in that all steps are performed in the presence of 4 M
guanidine hydrochloride and do not involve covalent modification of the mucin
molecule. Electrophoretic analyses and Western blotting showed that purified MG2
did not contain detectable levels of other salivary proteins. Amino acid analysis
showed that the composition of purified MG2 was in excellent agreement with the
deduced sequence of MG2 apomucin encoded in the MUC7 gene. The yield of purified
MG2 was 10-15 mg from 750 ml of salivary secretion. Binding of purified MG2 to
Streptococcus mutans in vitro was not significantly affected by reductive
methylation, but was nearly abolished by reduction and alkylation. These data
identified a functional determinant for mucin-bacterial interactions in the N
terminal region where the only two cysteines (Cys45 and Cys50) in the MG2
apomucin occur. Additionally, purified MG2 bound to four strains of oral
Streptococci, indicating that the binding is not dependent on complexing with
other salivary proteins, such as secretory immunoglobulin A. The purification
procedure described in this work will facilitate investigation of the role of MG2
in the oral environment.
PMID- 10190987
TI - Volume 312, number 1 (1994), in the article "Kinetics of enzymes with iso
mechanisms: dead-End inhibition of fumarase and carbonic anhydrase II," by karen
L. Rebholz and dexter B. Northrop, pages 227-233
PMID- 10190988
TI - Discourse deficits following right hemisphere damage in deaf signers.
AB - Previous findings have demonstrated that hemispheric organization in deaf users
of American Sign Language (ASL) parallels that of the hearing population, with
the left hemisphere showing dominance for grammatical linguistic functions and
the right hemisphere showing specialization for non-linguistic spatial functions.
The present study addresses two further questions: first, do extra-grammatical
discourse functions in deaf signers show the same right-hemisphere dominance
observed for discourse functions in hearing subjects; and second, do discourse
functions in ASL that employ spatial relations depend upon more general intact
spatial cognitive abilities? We report findings from two right-hemisphere damaged
deaf signers, both of whom show disruption of discourse functions in absence of
any disruption of grammatical functions. The exact nature of the disruption
differs for the two subjects, however. Subject AR shows difficulty in maintaining
topical coherence, while SJ shows difficulty in employing spatial discourse
devices. Further, the two subjects are equally impaired on non-linguistic spatial
tasks, indicating that spared spatial discourse functions can occur even when
more general spatial cognition is disrupted. We conclude that, as in the hearing
population, discourse functions involve the right hemisphere; that distinct
discourse functions can be dissociated from one another in ASL; and that brain
organization for linguistic spatial devices is driven by its functional role in
language processing, rather than by its surface, spatial characteristics.
PMID- 10190989
TI - A comparison of the codeswitching patterns of aphasic and neurologically normal
bilingual speakers of English and Spanish.
AB - Conversational discourse samples were obtained from four aphasic and four
neurologically normal Hispanic bilinguals in monolingual English, monolingual
Spanish, and bilingual contexts to identify codeswitching patterns. Analysis of
the samples based on the Matrix Language Frame (MLF) Model (Myers-Scotton, 1993a)
revealed consistent matching of the language context by the aphasic and normal
subjects. The aphasic subjects demonstrated a greater frequency of MLF
constituents and codeswitching patterns not evident in the speech samples of the
normal subjects. Results suggest an increased dependence on both languages for
communication following neurological impairment.
PMID- 10190990
TI - Cross-modal priming evidence for phonology-to-orthography activation in visual
word recognition.
AB - Subjects were asked to indicate which item of a word/nonword pair was a word. On
critical trials the nonword was a pseudohomophone of the word. RTs of dyslexics
were shorter in blocks of trials in which a congruent auditory prime was
simultaneously presented with the visual stimuli. RTs of normal readers were
longer for high frequency words when there was auditory priming. This provides
evidence that phonology can activate orthographic representations; the size and
direction of the effect of auditory priming on visual lexical decision appear to
be a function of the relative speeds with which sight and hearing activate
orthography.
PMID- 10190992
TI - Handbook of neurolinguistics. Edited By B. Stemmer and H. Whitaker. San diego:
academic press, 1997, xvii+790 pp
PMID- 10190991
TI - Decision latencies for phonological and semantic information in object
identification.
AB - Several on-line studies in the literature have been cited in support of a two
stage model of name-retrieval in which semantic processing precedes and mediates
access to phonology. Because of inconsistencies in prior studies an off-line
experiment was designed to provide converging evidence on this issue. An
experiment is reported in which young and elderly adults were required to give
speeded judgments of whether a pictured object matched a named category, a named
physical attribute, or a rhyming cue. Latencies for the young adults were fastest
for category judgments and slowest for rhyming judgments. For the elderly adults
physical attributes and rhyming judgments were equivalent. Results are discussed
in terms of "lemma" theory in object naming.
PMID- 10190993
TI - Impaired comprehension of raising-to-subject constructions in Parkinson's
disease.
AB - This paper describes an experiment which shows that roughly half of nondemented
patients with Parkinson's disease (PD) have impaired comprehension of subject-to
subject and object-to-subject raising constructions (e.g., Susan seems to Bill to
be tall and Susan is hard for Bill to catch), but have normal comprehension of
the counterpart constructions (e.g., It seems to Bill that Susan is tall and It's
hard for Bill to catch Susan). Several possible explanations for this pattern of
performance are considered, including a parsing disorder, a syntactic-semantic
linking disorder, a reduction of working memory capacity, slowed speed of
syntactic processing, and difficulty with the experimental task. Although some of
these explanations are arguably more plausible than others, the exact nature of
the comprehension impairment remains unclear.
PMID- 10190994
TI - Frequency of perseveration in normal subjects.
AB - Although perseveration is a recognized sign of disturbed brain function, it also
occurs in normal individuals. Determination of the frequency of perseveration in
normal subjects would enable clinicians to use perseveration as a marker of
possible pathology. The purpose of this study was to document the extent of
perseveration in normal young and older subjects. Thirty young normal individuals
between the ages of 20 and 35 years and 30 older normal individuals between the
ages of 60 and 75 years were given four tasks on which perseveration has been
reported in brain-damaged individuals. Four percent of all responses were
perseverative. No age or gender effects on frequency were observed. Of the four
neuropsychological tasks, the Modified Wisconsin Card Sorting Test elicited the
greatest number of perseverations.
PMID- 10190995
TI - Strategies of semantic categorization in the cerebral hemispheres.
AB - Strategies of semantic categorization in intact cerebral hemispheres were studied
in two experiments by presenting names of typical and atypical category instances
to the left visual field (LVF) (right hemisphere) or to the right visual field
(RVF) (left hemisphere). The results revealed that the typicality of instances
had a large effect on categorization times in the LVF in both experiments,
suggesting that the right hemisphere relies strongly on a holistic, similarity
based comparison strategy. In Experiment 1, the typicality effect was weaker in
the RVF than in the LVF. In Experiment 2, a typicality effect in the RVF was
observed for the "four-footed animal" category but not for the "bird" category.
The hypothesis that the left hemisphere employs a strategy based on defining or
necessary features is not supported by the observed typicality effect in the
"four-footed animal" category. Instead, it is suggested that the left hemisphere
may be able to categorize on the basis of prestored instance-category knowledge.
When such knowledge is not available (e.g., as for four-footed animals), a
similarity-based comparison strategy is employed by the left hemisphere.
PMID- 10190996
TI - Preattentive control of serial auditory processing in dichotic listening.
AB - Dichotic listening performance was examined in an auditory selective attention
task where subjects responded to occasional consonant-vowel (CV) or shaped
broadband noise-burst (NB) targets in rapid serial auditory presentation (RASP).
Trial types were randomized and included monaural CVs and NBs as well as dichotic
CV-CV and CV-NB pairings. CVs were spoken by two different voices (male and
female), and the two NB stimuli differed in their filter slopes at higher
frequencies. The target was designated by stimulus category (/ba/, /da/, /ga/, or
NB) and voice (e.g., "female /ba/"). Performance was compared for targets in the
left and right ears on monaural and dichotic trials using accuracy and reaction
time (RT) measures. Right ear advantages (REAs) were present for CV targets with
either CV or NB distractors, but not for monaural CVs. The REA found for monaural
NB targets was eliminated by CV distractors, yielding a left ear advantage (LEA)
for the distractor effect of CVs on NB targets. The pattern of results suggests
initial preprocessing of speech stimuli through phonetic feature analysis,
followed by serial attentional processing of the objects in the auditory field.
REAs are attributed to a rightward asymmetry in the preattentive control of
auditory attention similar to that found in visual search.
PMID- 10190997
TI - The critical period: some thoughts on Grimshaw et al (1998)
AB - Grimshaw et al. (1998), based on their study of an adolescent first language
acquirer, support the notion of a critical period. This article discusses the
findings of Grimshaw et al. in the context of second language acquisition
research. The study by Grimshaw et al. is argued to be of potentially significant
value in gaining an understanding of age-related differences in language
acquisition. Some issues for Grimshaw et al. to address are raised.
PMID- 10190998
TI - Simultaneous activation of reading mechanisms: evidence from a case of deep
dyslexia.
AB - We report the performance of LC, a deep dyslexic. We investigated extensively her
errors according to serial cognitive neuropsychological models of oral reading.
Initial evaluation of her reading suggested impaired access to the phonological
output lexicon (POL). Impaired grapheme-to-phoneme conversion (GPC) and semantic
errors in reading suggested that LC read via an impoverished semantic route.
However, a serial model of oral reading could not explain error differences in
reading, picture naming, spontaneous speech, and repetition. Neologisms occurred
in oral reading but not in spontaneous speech and repetition. Semantic errors in
naming exceeded those in oral reading. To account for these different error
patterns we propose that the semantic route, the direct route from the
orthographic input lexicon to the POL, and GPC activate simultaneously during
reading, converging at the POL to constrain phonological selection. These routes
are modular but not functionally encapsulated. For LC, the POL receives ambiguous
information due to degradation of all routes, causing reading errors.
PMID- 10190999
TI - Speech timing subsequent to brain damage: effects of utterance length and
complexity.
AB - Acoustic analyses of syllable durations were conducted in order to address
several hypotheses concerning deficits in the control of speech timing subsequent
to focal brain damage. Groups of nonfluent and fluent aphasics, right-hemisphere
damaged patients, and normal controls produced monosyllabic root syllables in
medial and final position in the context of short and long sentences and
syntactically simple and complex sentences. Durations of the target syllable as a
proportion of the utterance were compared across contexts and groups. Somewhat
surprisingly, the results revealed relatively normal temporal patterns in all
subject groups, with the main exception emerging for the nonfluent aphasic
patients who failed to demonstrate normal phrase-final lengthening effects.
Implications of the findings for theories of temporal control in brain-damaged
patients are considered.
PMID- 10191000
TI - The influence of neighborhood density on phonetic categorization in aphasia.
AB - The present study examined the contribution of lexically based sources of
information to acoustic-phonetic processing in fluent and nonfluent aphasic
subjects and age-matched normals. To this end, two phonetic identification
experiments were conducted which required subjects to label syllable-initial
bilabial stop consonants varying along a VOT continuum as either /b/ or /p/.
Factors that were controlled included the lexical status (word/nonword) and
neighborhood density values corresponding to the two possible syllable
interpretations in each set of stimuli. Findings indicated that all subject
groups were influenced by both lexical status and neighborhood density in making
phonetic categorizations. Results are discussed with respect to theories of
acoustic-phonetic perception and lexical access in normal and aphasic
populations.
PMID- 10191001
TI - The Effects of Resistance to Shift of the Equilibrium State of a Liquid Droplet
in Contact with a Solid.
AB - The effect of blocking the shift of the contact surface between a liquid drop and
a solid body is discussed. The model proposed in (S. D. Iliev, 1997, J. Colloid
Interface Sci., 194, 287) is discussed. This equilibrium model considers the
resistance to shift by adding an energy to the classical capillary equilibrium
model. It is shown that the set of equilibrium shapes of static droplets is
effectively modeled. Studying the set of equilibrium axisymmetric drops, located
on a horizontal surface, the analysis proves that the contact angle hysteresis is
described without introducing a dependence between the resistance-to-shift
coefficients and the drop volume and Bond's number. A possibility of realizing a
stick-slip motion and division of the equilibrium drops is studied, too. It is
shown that the equilibrium model describes also the set of equilibrium
nonaxisymmetric static drops. The everyday experience to obtain the various
nonaxisymmetric drop shapes by the deforming of contact line with a thin rod is
numerically modeled. Copyright 1999 Academic Press.
PMID- 10191002
TI - Effect of Cationic Micelles on the Kinetics of Interaction of Ninhydrin with l
Leucine and l-Phenylalanine.
AB - The effect of cationic micelles of cetyltrimethylammonium bromide (CTAB) and N
cetylpyridinium bromide (CPB) on the interaction of l-leucine and l-phenylalanine
with ninhydrin have been studied at 70 degrees C. Both surfactants strongly
catalyze the reactions. The reaction rates are higher in CTAB micelles than in
CPB micelles. Quantitative kinetic analysis has been performed on the basis of a
pseudo-phase model. The influence of different salts on the reaction rates has
also been seen and it is found that tightly bound/incorporated counterions are
the most effective. Copyright 1999 Academic Press.
PMID- 10191003
TI - Self-Assembled Supramolecular Micellar Structures Based on Non-ionic Surfactants
and Cyclodextrins.
AB - The complexation between non-ionic polyethylene oxide (PEO)-based surfactants
(Triton X-45, Triton X-100, polyethylene glycol-1000-monostearate, and Brij 35)
and cyclodextrins is studied. It is shown that the addition of surfactant
solutions to the aqueous solution of alpha, beta-, and gamma-cyclodextrins
affords poorly soluble crystalline precipitates. Parameters of crystalline
structure and the composition of complexes are analogues to those obtained on the
basis of polyethylene oxide. Using a method of surface tension it is shown that
cyclodextrins favor the increase of the value of critical micelle concentration
(CMC) of surfactants. The dependence of CMC from the molar ratio
cyclodextrin/surfactant permits us to determine the composition of inclusion
complexes in solution. For Triton X-100 and polyethylene glycol-1000-monostearate
values of stoichiometric composition of complexes in solution and in condensed
phase agree well. It is shown that in the presence of beta-cyclodextrin the
destruction of micelles based on Triton X-100 occurs. UV-spectroscopy is used for
the investigation of the microenvironment of a phenyl group in inclusion
complexes based on alpha- and beta-cyclodextrins. The interaction of gamma
cyclodextrin with PEO surfactants results in the formation of novel double-tailed
surfactants. The values of CMC registered in solutions of these complexes is
lower than the corresponding value of Triton X-100 and polyethylene glycol-1000
monostearate. The stoichiometric composition of complexes in solution is
established from the dependence of CMC versus the gamma-cyclodextrin/surfactant
ratio. The composition of the complexes in solution and condensed phase agree
well. The interaction of alpha- and gamma-cyclodextrins with Brij 35 results in
the formation of nonstoichiometric complexes. The investigation of the
dependences of CMC of modified surfactants from temperature shows that these
supramolecular structures exist at high temperatures. Copyright 1999 Academic
Press.
PMID- 10191004
TI - Mechanism of Formation of Monodispersed Colloids by Aggregation of Nanosize
Precursors.
AB - It has been experimentally established in numerous cases that precipitation of
monodispersed colloids from homogeneous solutions is a complex process.
Specifically, it was found that in many systems nuclei, produced rapidly in a
supersaturated solution, grow to nanosize primary particles (singlets), which
then coagulate to form much larger final colloids in a process dominated by
irreversible capture of these singlets. This paper describes a kinetic model that
explains the formation of dispersions of narrow size distribution in such
systems. Numerical simulations of the kinetic equations, with experimental model
parameter values, are reported. The model was tested for a system involving
formation of uniform spherical gold particles by reduction of auric chloride in
aqueous solutions. The calculated average size, the width of the particle size
distribution, and the time scale of the process agreed reasonably well with the
experimental values. Copyright 1999 Academic Press.
PMID- 10191005
TI - Surface Enhanced Raman Spectroscopic Study of Isomeric Methylthiophenes in Silver
Colloid.
AB - Surface Enhanced Raman Spectra (SERS) of 2-methylthiophene (2-MT) and 3
methylthiophene (3-MT) in silver colloid are compared with their normal Raman
spectra in the bulk and in acetonitrile solution. Experimental results indicate
that both the methylthiophene molecules are adsorbed on a metal surface through
the sulfur atom. Assuming the image dipole theory to be valid, the observed
surface enhancement factor of the C-H stretching mode in 2-MT indicates that the
C-H bond of this isomer makes an angle of 51 degrees with the surface normal. The
experimental results further suggest that the 3-MT molecule is adsorbed with its
ring plane almost vertical to the metal surface; the 2-MT molecule, on the other
hand, is tilted more than 45 degrees to the surface normal. The concentration
dependence of the relative enhancement factor indicates that a monomolecular
layer is formed on the metal surface at a specific concentration of the
methylthiophenes in silver sol. No oligomerization of the two methylthiophenes on
the silver surface is observed. Copyright 1999 Academic Press.
PMID- 10191006
TI - Twisted Intramolecular Charge Transfer Emission of 2-(4'-N,N
dimethylaminophenyl)benzimidazole in Micelles.
AB - Spectral characteristics of 2-(4'N,N-dimethylaminophenyl)benzimidazole have been
studied as a function of surfactant concentration and as a function of acid
concentration in three surfactants. Dual fluorescence is observed in all the
micelles. Fluorescence intensities of the local emission (B band) and twisted
intramolecular charge transfer (A band, TICT) increase by an 17-30% and 38 to 64%
respectively. When dissolved in micelles lifetimes of both the states also
increase in the presence of micelles. The increase in the fluorescence
intensities is attributed to the decrease in the non-radiative decay constant.
cmc of the surfactants can be determined from the variation in the fluorescence
intensity and the lifetime data. The equilibrium constants are determined for the
prototropic reactions of the fluorophore in all the micelles in S0 and S1 states
and the values obtained are discussed. Copyright 1999 Academic Press.
PMID- 10191007
TI - Synthesis and Structural Ordering of Gradient-Modulus Star Copolymers.
AB - Gradient-modulus star copolymers were synthesized by crosslinking of
polystyrene/isoprene tapered anions with divinylbenzene in benzene. The styrene
content in the tapered arm was determined by 1H-nuclear magnetic resonance as a
parameter of conversion. The composition of the arm showed the gradient structure
and was in good agreement with that calculated by reactivity ratios. The solution
properties of gradient-modulus star copolymers were examined by static and
dynamic light scatterings. The structural ordering of gradient-modulus star
copolymers were investigated by means of small-angle X-ray scattering. Gradient
modulus star copolymers formed a body-centered cubic (BCC) structure near the
overlap threshold (C*). Above C*, this structure changed to the mixed lattice of
BCC and face-centered cubic (FCC) structures. Copyright 1999 Academic Press.
PMID- 10191008
TI - Use of Micellar-Enhanced Ultrafiltration at Low Surfactant Concentrations and
with Anionic-Nonionic Surfactant Mixtures.
AB - Micellar-enhanced ultrafiltration is a separation technique which can be used to
remove metal ions or dissolved organics from water. Metal ions bind to the
surface of negatively charged micelles of an anionic surfactant while organic
solutes tend to dissolve or solubilized within the micelles. The mixture is then
forced through an ultrafiltration membrane with pore sizes small enough to block
passage of the micelles and associated metal ions and/or dissolved organics.
Monomeric or unassociated surfactant passes through the membrane and does not
contribute to the separation. This paper considers advantages of addition of
small concentrations of nonionic surfactant to an anionic surfactant; the
resulting anionic-nonionic mixed micelles exhibit negative deviation from
ideality of mixing which leads to a smaller fraction of the surfactant being
present as monomer and a subsequently larger fraction present in the micellar
form. The addition of nonionic surfactant improved the separation of divalent
zinc substantially at total concentrations above the critical micelle
concentration (cmc) of the anionic surfactant. Both zinc and tert-butylphenol (a
nonionic organic solute) show unexpected rejection at surfactant concentrations
moderately below the cmc, where micelles are absent. This is considered as due to
a higher surfactant concentration in the gel layer adjacent to the membrane where
micelles are present. Reduction of this rejection at lower transmembrane pressure
drops supports this mechanism. Some rejection of zinc was observed in the absence
of surfactant but not of tert-butylphenol, indicating an additional effect of
membrane charge for ionic solutes. Copyright 1999 Academic Press.
PMID- 10191009
TI - Pseudo First-Order Cleavage of an Immobilized Substrate by an Enzyme Undergoing
Two-Dimensional Surface Diffusion.
AB - In this paper we study the reaction kinetics of an enzyme adsorbed on a peptide
substrate surface. Although the adsorption is effectively irreversible, the
enzyme is able to diffuse on the surface. Our reaction system consisted of the
enzyme collagenase and the oligopeptide FALGPA, a substrate for the enzyme. A
quartz surface was coated with covalently bound substrate molecules. The extent
of reaction was monitored continuously in a flow cell via UV absorption. The data
are compatible with a kinetic model based on a pseudo first-order
diffusion/orientation rate-limiting step followed by a relatively fast chemical
cleavage step. This model was validated by examining the pH dependence of the
rate constant. Copyright 1999 Academic Press.
PMID- 10191010
TI - Influence of Alkyl Chain Length and Structure on the Extraction of Copper(II)
from Aqueous Acid by 5-Alkyl-2-hydroxybenzaldoximes in Hydrocarbon Solvents:
Diffusion Coefficients of Extractants and Their Complexes.
AB - Measurement of the kinetics of extraction of copper(II) by 19 different 5-alkyl-2
hydroxybenzaldoximes (alkyl is C7H15 and C9H19) from acidic (hydrogen sulfate
buffer) aqueous solution in the range pH 3.4-2.0, into 20% v/v toluene in n
hexane is reported. The lowering of the interfacial tension has been measured in
some cases. The solubility of the extractants in water has been measured
spectrophotometrically. A modified Taylor-Aris dispersion technique has been used
to measure the diffusion coefficients in n-hexane and Orfom SX7 of some of the
extractants and of the copper(II) complexes which they form. At low initial bulk
concentrations (<10 mol m-3) of the extractants, the rate of extraction is
controlled by the rate of diffusion of the extractant from the bulk to the
organic-aqueous interface. The diffusion coefficient is related to the steric
bulk of the alkyl substituent. At higher initial bulk concentrations (200 mol m
3) of the extractants, when the interface is saturated, the rate of extraction is
inversely related to the apparent steric bulk of the alkyl substituent. Copyright
1999 Academic Press.
PMID- 10191011
TI - Breakup of a Multiple Emulsion Drop in a Uniform Electric Field.
AB - The steady deformation and breakup of emulsion drops in a uniform electric field
are considered experimentally. Due to the low volume fraction of inner drops, the
emulsions can be effectively assumed as Newtonian fluids with spatial
nonuniformity. The measurements of the electrical properties show that the oil-in
water (o/w) emulsion drop behaves like a conducting drop. On the other hand, the
water-in-oil (w/o) emulsion drops can be regarded as inhomogeneous leaky
dielectric drops. It is found that the viscosity ratio is not an important
parameter within the small deformation limit and breakup mode of the o/w emulsion
drops. In the case of w/o emulsion drops, however, the breakup mode depends on
the viscosity ratio. Inherent nonuniformity of the emulsion drops makes drop more
deformable and unstable. The tip-streaming is the dominant breakup mode of o/w
emulsion drops when the nonuniformity of drop phase is appreciable. Copyright
1999 Academic Press.
PMID- 10191012
TI - Exact and Approximate Expressions for Bubble-Particle Collision.
AB - The flotation microprocess of collision is investigated and an exact expression
for the probability of collision (Pc) is developed based on the intermediate flow
of Yoon and Luttrell (1). This expression for Pc only assumes that the bubble and
particle are spherical and that the particle radius is less than the bubble
radius (i.e., Rp < RB). In addition to removing the requirement that Rp << RB,
the influence of a particle settling velocity is also included in the model
development. The expression for Pc is shown to be a function of three
dimensionless groups: (i) the magnitude of the dimensionless particle settling
velocity, ||G ||; (ii) the bubble Reynolds number, ReB; and (iii) the ratio of
particle to bubble radius, Rp/RB. The probability of collision model is compared
to available experimental data and good agreement is shown. A parametric study is
also completed for 0 = ||G || = 1, 0 = ReB = 500, and 0.001 = Rp/RB <
1. In general, Pc is independent of ReB when Rp/RB less, similar 0.03, the
particle settling velocity is important for small values of Rp/RB, and Rp/RB
dominates as Rp/RB --> 1. Copyright 1999 Academic Press.
PMID- 10191013
TI - The Physicochemical Behavior of Phytosterol Ethoxylates.
AB - In this work the physicochemical behavior of a series of phytosterol ethoxylates
in water is presented. The influence of the length of the polyoxyethylene chain
is studied. The surfactant solutions have been examined by means of birefringent
microscopy, surface tension, self-diffusion 1H NMR, dynamic and static light
scattering, and rheology. The surfactants with a hydrophilic chain of 10
oxyethylene units or more gave a micellar region. The CMC values were generally
very low and a reverse relationship between the CMC value and the polyoxyethylene
chain length was obtained. The time required to reach equilibrium surface tension
was very long, more than 150 min. For the hydrophobic surfactants large lamellar
regions appeared while for the more hydrophilic surfactants cubic and hexagonal
structures were present which remained stable up to temperatures of 100 degrees
C. In the micellar region prolate aggregates were formed which showed "ghostlike"
behavior, consisting of cross-linked micelles with very fast relaxation times.
Copyright 1999 Academic Press.
PMID- 10191014
TI - Computer Simulations for the Growth Process of Peanut-Type Hematite Particles.
AB - The growth process of a monodispersed peanut-type hematite particle consisting of
much smaller elongated subcrystals has been reproduced by computer simulation. On
the basis of the microscopic internal structure, the simulation was performed by
replacing the sequential events of surface nucleation and the subsequent growth
of each subcrystal in the actual process with an arranged deposition of
rectangular segments of fixed dimensions under different conditions in their site
dependent deposition rate and in the flexibility of their tilt angles. The most
successful simulation model was obtained on the assumptions of a relatively fast
deposition of the segments on the outermost side-surface of the ellipsoidal
particle and the flexible tilt angle of each segment depending on the position of
a neighboring new segment placed afterward. The result of the simulation strongly
supported the previous elucidation of the growth mechanism in terms of the
outward bending of adjoining subcrystals by nucleation and growth of a new
subcrystal in each space between them. Enhancement of the outward bending of
subcrystals by a large amount of sulfate ions adsorbed to the growing subcrystals
was also suggested. Copyright 1999 Academic Press.
PMID- 10191015
TI - Study of the Interaction Products of Some N- and O-Containing Compounds with
Highly Dispersed Copper(II) Hydroxide.
AB - Composition and structure of the surface compounds formed after interaction
between Cu(OH)2 supported on aerosil and bpy, py, PhOH, and H2O2 are studied. The
EXAFS and electron spectroscopy methods show the main part of copper ions to
remain in a hydroxide surrounding, whose structure does not change practically
and does not depend on the nature of the extra ligands used. The colloidal
Cu(OH)2 stabilized by starch is found to reveal the same properties as the
supported one, but differs by greater sizes of hydroxide particles. Copyright
1999 Academic Press.
PMID- 10191016
TI - Thermodynamics of Interaction between Some Cellulose Ethers and SDS by Titration
Microcalorimetry.
AB - The interaction between certain nonionic cellulose ethers (ethyl hydroxyethyl
cellulose and hydroxypropyl methyl cellulose) and sodium dodecyl sulphate (SDS)
has been investigated using isothermal titration microcalorimetry at temperatures
between 25-50 degrees C. The observed heat flow curves have been interpreted in
terms of a plausible mechanism of the interaction of the substituent groups with
SDS monomers and clusters. The data have been related to changes occuring in the
system at the macro- and microscopic levels with the addition of surfactants and
with temperature. The process consists predominantly of polymer-surfactant
interactions initially and surfactant-surfactant interactions at the later
stages. A phenomenological model of the cooperative interaction (adsorption)
process has been derived, and earlier published equilibrium binding data have
been used to recover binding constants and Gibbs energy changes for this process.
The adsorption enthalpies and entropies have been recovered along with the heat
capacity change. The enthalpic cost of confining the nonpolar regions of the
polymers in surfactant clusters is high, but the entropy gain from release of
hydration shell water molecules as well as increased freedom of movement of these
nonpolar regions in the clusters gives the process a strong entropic driving
force. The process is entropy-driven initially and converts to being both
enthalpy and entropy-driven at high SDS concentrations. An enthalpy-entropy
compensation behavior is seen. Strongly negative heat capacity changes have been
obtained resulting from the transfer of nonpolar groups from aqueous into
nonpolar environments, as well as a reduction of conformational domains that the
chains can populate. Changes in these two components cause the heat capacity
change to become less negative at the higher binding levels. The system can be
classified as exhibiting nonclassical hydrophobic binding at the later stages of
binding. Copyright 1999 Academic Press.
PMID- 10191017
TI - Thermodynamics of Interaction between Some Cellulose Ethers and SDS by Titration
Microcalorimetry.
AB - A titration calorimetric study of the interaction between nonionic cellulose
ethers and ionic surfactant (SDS) has been extended to a larger number of
polymers to explore the effect of variation of polymer hydrophobicity on the
energetics of the process. "Hydrophobicity" as used here is an overall effect of
the nature, degree, and number of substituents and is characterized by the cloud
point and (aqueous) surface tension lowering abilities of the polymer. A direct
correlation is found between the extent of "hydrophobicity" and the endo
enthalpic peak in the initial SDS concentration region of interaction. However,
the overall mechanism of interaction is similar for all the polymers, being
dominated by polymer-surfactant interactions initially and converting into a
surfactant-surfactant interaction process at higher SDS concentrations. The
importance of polymer characteristics thus becomes weaker at the later stages of
the process. Differences between the polymers is also reduced by an increase of
temperature, leading to a near overlap of observed enthalpy curves at 40 degrees
C. The energetics of interaction are also mirrored by the isothermal surfactant
binding curves and the changes in macroscopic and microviscosity of the system.
Copyright 1999 Academic Press.
PMID- 10191018
TI - Molecular Weight Effect on Latex Film Formation from Polystyrene Particles: A
Photon Transmission Study.
AB - The photon transmission method was used to probe the time evolution of film
formation from latex particles. Two different latex films were prepared from high
molecular weight (HM) and low molecular weight (LM) polystyrene particles at room
temperature and were annealed at various temperatures in 2.5-min time intervals
above the glass transition. The increase in the transmitted photon intensity
(Itr) is attributed to the increase in "crossing density" at the junction
surface. The Prager-Tirrell model was employed to interpret the increase in
crossing density at the junction surface. The back and forth activation energies
were measured for HM and LM films and found to be around 59 and 87 kcal/mol for a
reptating polymer chain across the junction surface. Monte Carlo simulations were
performed for photon transmission through a rectangular lattice. The number of
transmitted photons (Ntr) was calculated as a function of the mean free path of
photons. It was observed that Ntr, similar to Itr, increases as the square of the
mean free path of photons is increased. Copyright 1999 Academic Press.
PMID- 10191019
TI - Shear-Induced "Melting" of an Aqueous Foam.
AB - We present diffusing-wave spectroscopy measurements of bubble dynamics in a
continuously sheared aqueous foam. At slow strain rates, isolated clusters of
bubbles intermittently rearrange from one solidly packed configuration to
another, even though the macroscopic flow appears continuous. At fast rates,
bubbles instead move smoothly and continuously throughout the entire foam. In
other words, shear flow that appears macroscopically laminar is similarly laminar
down to the bubble scale; effectively the foam "melts." The crossover to this
regime can be understood in terms of elastic energy accumulation and viscous
dissipation mechanisms. In particular, the strain rate needed for shear-induced
melting to occur is set by the ratio of a yield strain to the rearrangement event
duration. To explore the implications for macroscopic flow, we compare these
bubble-scale dynamics directly with viscosity measurements. Copyright 1999
Academic Press.
PMID- 10191020
TI - Direct Observation of Foam Film Rupture by Several Types of Antifoams Using a
Scanning Laser Microscope.
AB - It is well known that the stability of a pseudoemulsion film, a thin liquid film
formed between an antifoam particle and air, can be important during defoaming
action. We have compared the bursting behavior of a two-dimensional thin liquid
film from an aqueous surfactant solution on a glass plate, in which six types of
antifoam particles have been dispersed, using laser microscopic techniques. The
used antifoams were a silicone oil, a mixed-type antifoam (mixture of silicone
oil and hydrophobic solid particles), a hydrophobic silica, and a silicone-based
solid antifoam (prepared by interfacial polymerization with oil and water). The
antifoaming performance of these six types of antifoams, measured by the glass
cylinder shaking test, was in the order: the mixed-type antifoam >== the silicone
based solid antifoam > the hydrophobic silica >== the silicone oil.
Pseudoemulsion film rupture was observed at the film thickness less than 0.1 um
for both the silocone oil and the hydrophobic silica. In the case of particles
with rough edges (the silicone-based antifoam), pseudoemulsion film on the top of
the particles can be easily ruptured at a convex part of the solid surface.
Furthermore, solid particles existing on the surface of an oil droplet in the
mixed-type antifoams form marked projections and these projections give rise to
distortion of the thinning film. As soon as the distortion of the thinning film
took place on the top of the antifoam droplet, the pseudoemulsion film can be
instantaneously ruptured. Referring to the antifoaming mechanisms for mixed-type
antifoams, both steps from the pseudoemulsion film formation to the lens
formation and from the counter pseudoemulsion film formation to the bridge
formation would be very fast and cause a very high antifoaming efficiency.
Copyright 1999 Academic Press.
PMID- 10191021
TI - Photorheological Effects in Aqueous Micellar Tetramethylammoniumhydrogen-2
dodecyl Malonate via Photodimerization of Acridizinium Bromide.
AB - Aqueous solutions of tetramethylammoniumhydrogen-2-dodecyl malonate (TMHM) were
investigated rheologically in the absence and presence of monomeric and
photodimerized acridizinium bromide as solubilizates. Upon constant shearing a
viscosity increase (accompanied by viscoelasticity) was observed in a certain
range of TMHM concentration after an induction period. This indicates the
formation of shear induced structures. Viscoelasticity was characterized via
stress relaxation experiments revealing a single relaxation process with time
constants of 0.2-0.3 s mostly. At certain shear rates a temporal oscillation of
viscosity was observed. In the presence of acridizinium bromide the elasticity
was reduced and the TMHM concentration range of viscoelastic flow was narrowed
while relaxation time constants remained constant. Photodimerization of
acridizinium bromide (performed in situ) reverted the effects induced by the
monomers. Copyright 1999 Academic Press.
PMID- 10191022
TI - Structure-Function Analysis of the Emulsifying and Interfacial Properties of
Apomyoglobin and Derived Peptides.
AB - Apomyoglobin was chosen as a model to study the emulsifying properties of
proteins. It was cleaved into three peptides using cyanogen bromide and these
peptides were purified and tested for emulsifying and interfacial properties. Two
of the peptides had improved emulsifying activity compared to the whole protein.
The peptide (residues 1-55) with the highest emulsifying activity and whole
apomyoglobin were studied further. The amount of protein or peptide adsorbed at
the oil-water interface of an emulsion was measured and the surface area occupied
per molecule was calculated. For apomyoglobin, at maximal surface coverage each
molecule occupied a surface area of approximately 8 nm2. This is consistent with
a packed monolayer, based on the approximate dimensions of apomyoglobin. For
peptide (1-55), at maximal surface coverage each molecule occupied a surface area
of approximately 3 nm2. This is consistent with the area that the two amphipathic
alpha-helices which are potentially present in this molecule would cover, if they
were aligned along the oil-water interface. The different structural
characteristics of these molecules responsible for their emulsifying properties
are discussed. Copyright 1999 Academic Press.
PMID- 10191023
TI - Adsorption Behavior of Iron-Cyanide onto gamma-Al2O3 Interface: A Coagulation
Approach.
AB - Ferrocyanide and ferricyanide ions have strong coagulation ability in a natural
water system due to their high valences. Studies with aluminum oxide turbid
waters showed significant differences in coagulation between simple ions (Cl-,
SO2-4, Fe(CN)3-6, Fe(CN)4-6) and other species (H2PO-4) that interact chemically
with the oxide surface. The evidence suggested that the adsorption of
ferrocyanide and ferricyanide on aluminum oxide surface is an outer-sphere
reaction. The linear relationship between the logarithm of the significant
coagulation concentration and Schultz-Hardy ratios indicated that the coagulation
obeyed the DLVO rule. Therefore, it is concluded that the coagulation of aluminum
oxide by ferrocyanide and ferricyanide is essentially caused by compression of
the electric double layer rather than by charge neutralization. Copyright 1999
Academic Press.
PMID- 10191024
TI - Measurement of Catalytic Reaction Kinetics for Adsorbed Enzyme Monolayers.
AB - We present a new assay based on total internal reflection fluorescence (TIRF) to
quantify the catalytic activity of adsorbed enzyme monolayers on macroscopically
flat surfaces. The need for such an assay derives from a general shortage of
assay methods that are sufficiently sensitive to measure reaction kinetics for
just a single monolayer of enzymes. The assay is based on the enzymatic
conversion of a soluble, nonfluorescent fluorogenic substrate reagent to a
soluble, highly fluorescent product. The reaction occurs at the solid-liquid
interface where the enzymes are adsorbed. Fluorogenic substrates are introduced
to the adsorbed layer by convective diffusion from solutions undergoing steady
laminar slit flow. The exponentially decaying evanescent wave that is produced by
total internal reflection serves as a "spectroscopic ruler" to resolve the
spatial concentration profile of fluorescent products in solution near the
interface. By measuring the steady-state fluorescence signal as a function of the
Peclet number that characterizes mass transfer conditions in the experiment, it
is possible to determine the enzymatic reaction rate. Here we present the
development of the method and its application to a test system of beta
galactosidase adsorbed to methylated silica surfaces. Compared to the enzymatic
rate constants for this enzyme in free solution, adsorption decreased the
Michaelis-Menten rate constant kcat by a factor of 10 and increased the
equilibrium binding constant Km by a factor of 4.5. Thus the intrinsic activity
of the enzyme, as represented by the ratio kcat/Km, decreased 45-fold due to
adsorption. Copyright 1999 Academic Press.
PMID- 10191025
TI - Dynamics of Drop Formation in an Electric Field.
AB - The effect of an electric field on the formation of a drop of an inviscid,
perfectly conducting liquid from a capillary which protrudes from the top plate
of a parallel-plate capacitor into a surrounding dynamically inactive, insulating
gas is studied computationally. This free boundary problem which is comprised of
the surface Bernoulli equation for the transient drop shape and the Laplace
equation for the velocity potential inside the drop and the electrostatic
potential outside the drop is solved by a method of lines incorporating the
finite element method for spatial discretization. The finite element algorithm
employed relies on judicious use of remeshing and element addition to a two
region adaptive mesh to accommodate large domain deformations, and allows the
computations to proceed until the thickness of the neck connecting an about to
form drop to the rest of the liquid in the capillary is less than 0.1% of the
capillary radius. The accuracy of the computations is demonstrated by showing
that in the absence of an electric field predictions made with the new algorithm
are in excellent agreement with boundary integral calculations (Schulkes, R. M.
S. M. J. Fluid Mech. 278, 83 (1994)) and experimental measurements on water drops
(Zhang, X., and Basaran, O. A. Phys. Fluids 7(6), 1184 (1995)). In the presence
of an electric field, the algorithm predicts that as the strength of the applied
field increases, the mode of drop formation changes from simple dripping to
jetting to so-called microdripping, in accordance with experimental observations
(Cloupeau, M., and Prunet-Foch, B. J. Aerosol Sci. 25(6), 1021 (1994); Zhang, X.,
and Basaran, O. A. J. Fluid Mech. 326, 239 (1996)). Computational predictions of
the primary drop volume and drop length at breakup are reported over a wide range
of values of the ratios of electrical, gravitational, and inertial forces to
surface tension force. In contrast to previously mentioned cases where both the
flow rate in the tube and the electric field strength are nonzero, situations are
also considered in which the flow rate is zero and the dynamics are initiated by
impulsively changing the field strength from a certain value to a larger value.
When the magnitude of the step change in field strength is small, the results of
the new transient calculations accord well with those of an earlier stability
analysis (Basaran, O. A., and Scriven, L. E. J. Colloid Interface Sci. 140(1), 10
(1990)) and thereby provide yet another testament to the accuracy of the new
algorithm. Copyright 1999 Academic Press.
PMID- 10191026
TI - Chemical Force Microscopy Study of Adhesion and Friction between Surfaces
Functionalized with Self-Assembled Monolayers and Immersed in Solvents.
AB - Adhesive and frictional forces between surfaces modified with self-assembled
monolayers (SAMs) and immersed in solvents were measured with chemical force
microscopy as functions of surface functionality and solvent. Si/SiO2 substrates
were modified with SAMs of alkylsiloxanes (SiCl3(CH2)n-X), and gold-coated AFM
tips were modified with SAMs of alkylthiolates (HS-(CH2)n-X). SAMs of
alkylsiloxanes terminated in a methyl or oxidized vinyl group; SAMs of
alkanethiolates terminated in a methyl or carboxyl group. Adhesive and frictional
forces were measured in hexadecane, ethanol, 1,2-propanediol, 1,3-propanediol,
and water. The work of adhesion (W) was calculated with the Johnson-Kendall
Roberts theory of adhesive contact. The JKR values agreed well with values
derived from the Fowkes-van Oss-Chaudhury-Good surface tension model and from
contact angle results. Calculated values of W for all combinations of contacting
surfaces and solvents spanned two orders of magnitude. W correlated with the
surface tension of the solvent for hydrophobic/hydrophobic interactions;
hydrophilic/hydrophilic and hydrophobic/hydrophilic interactions were more
complex. Friction forces were fit to a modified form of Amonton's law. For any
solvent, friction coefficients were largest for the hydrophilic/hydrophilic
contacting surfaces. The friction coefficient for any contacting pair was largest
in hexadecane. In polar solvents, friction coefficients scaled with solvent
polarity only for hydrophobic/hydrophobic contacting pairs. Copyright 1999
Academic Press.
PMID- 10191027
TI - Combined Water and the Ion Exchange Characteristics of Manganese Dioxide Produced
by Ozonation.
AB - The change in ion exchange properties of manganese dioxide produced by ozonation
(OMD) was studied with respect to its preheated temperature. This was performed
by heating samples to different temperatures and later, saturating a part of them
in aqueous cadmium sulfate solutions. Analyses were practiced on both the cadmium
ion exchanged and un-ion exchanged samples. Results showed that the ion exchange
reaction followed a stoichiometric relation between the hydrogen and cadmium
ions, promoted by the combined water. The molar ratio of combined water to
exchanged cadmium was found to be five. X rays and photographs taken in the
scanning electron microscope showed that the structure and morphology of the OMD
were not modified by the insertion of the cadmium during ion exchange. From the X
rays, the structure of the OMD was determined to be of the gamma type. When the
samples were heated to 400 and 500 degrees C, the crystal structure changed to
beta and finally to Mn2O3, respectively. However, the changes in structure alone
apparently did not affect the ion exchange. The surface area, measured by the BET
technique, diminished linearly with the preheat temperature. The ion exchanged
cadmium and the surface area showed a nonlinear relationship. However, the
surface area and the quantity of combined water in the OMD were both linearly
affected by preheating and are directly related to the ion exchange capacity.
Copyright 1999 Academic Press.
PMID- 10191028
TI - Effect of Particle Size on Rate of Coalescence of Silica Nanoparticles.
AB - In high temperature processes, at high concentrations, aerosol particles grow by
collisions and coalescence. The rate of coalescence is an important parameter for
predicting the final primary particle size. For some materials, particularly
silica, predictions of final primary particle size using coalescence rates based
upon bulk material properties are not in agreement with experimental results. One
explanation may be that the high internal pressure in very small particles (less
than 10 nm in diameter) affects the mobility of material within the particles and
hence the coalescence rate. In this Note, a new approach for estimating rates of
coalescence of particles in the initial stages of growth is presented.
Coalescence of liquid particles is assumed to be rate-limited by atomic mobility,
and the effect of internal pressure on diffusivity is considered. Copyright 1999
Academic Press.
PMID- 10191029
TI - Titration Microcalorimetry Studies of the Interaction between Humicola lanuginosa
Lipase and Ionic Surfactants.
AB - Microcalorimetry has been used to study the interaction between Humicola
lanuginosa lipase and either the anionic surfactant sodium dodecyl sulfate, SDS,
or the cationic surfactant tetradecyltrimethylammonium bromide, TTAB. For SDS no
conclusive evidence was obtained of whether or not an enzyme-surfactant complex
is formed. Although not unambiguous, the calorimetric titration curves obtained
with TTAB indicate formation of such a complex. Copyright 1999 Academic Press.
PMID- 10191030
TI - A Mechanistic Approach to Modeling Single Protein Adsorption at Solid-Water
Interfaces.
AB - A kinetic model for single component protein adsorption which can be readily
extended to adsorption from multi-protein solutions was developed, and used to
simulate adsorption of site-directed, structural stability mutants of
bacteriophage T4 lysozyme. The model allows for two different adsorbed "states,"
distinguished by different binding strengths and different occupied areas. The
presence of an increasing energy barrier to adsorption was incorporated into the
model by formulating the adsorption rate constants as functions of time.
Numerical analysis was performed using the Marquardt method. Estimated model
parameters were consistent with the effect of structural stability on adsorption.
In particular, kinetic parameters were such that adsorption into the more tightly
bound, conformationally altered state was favored by less stable variants.
Copyright 1999 Academic Press.
PMID- 10191031
TI - Long-Range Electrostatic Attractions between Identically Charged Particles in
Confined Geometries: An Unresolved Problem.
AB - Long-range electrostatic attractions between identical colloidal particles in
confined geometries have been observed experimentally by many workers. A
satisfactory theoretical explanation for this behavior has proven elusive. Recent
numerical calculations and reports (Nature 393, 621-623, 663-665 (1998)),
however, have suggested that this problem is closed by demonstrating that this
surprising effect is to be found naturally within the well-established Poisson
Boltzmann (PB) theory. We rigorously prove that these claims are false; within
the framework of the PB theory, the interaction between identical colloidal
particles is always repulsive, irrespective of whether the particles are isolated
or confined. A satisfactory theoretical explanation of this surprising phenomenon
thus remains an unresolved problem. Copyright 1999 Academic Press.
PMID- 10191032
TI - Preparation and Characterization of Nanoscopic Organic Semiconductor of
Oxovanadium Phthalocyanine.
AB - Nanoscopic particles of oxovanadium phthalocyanine (VOPc, phase-II) with
different particle sizes are prepared by aggregation of VOPc molecules in the
presence of surfactants for the first time. A size effect in the region of
nanoscale was observed in the UV-visible spectra. The photoconductivity of the
nanoscopic VOPc is much higher than that of bulk VOPc. Copyright 1999 Academic
Press.
PMID- 10191033
TI - Cryopreservation of bovine in vitro produced embryos using ethylene glycol in
controlled freezing or vitrification.
AB - In this study, the cryoprotectant ethylene glycol (EG) was tested for its ability
to improve and facilitate the cryopreservation of in vitro produced (IVP) bovine
embryos. Embryos were cryopreserved in EG solutions supplemented with either
newborn calf serum (NBCS) or polyvinyl alcohol (PVA). To assess EG toxicity, the
embryos were equilibrated in EG concentrations from 1.8 to 8.9 M at room
temperature for 10 min and then cultured for 72 h on a cumulus cell monolayer.
The hatching rate was highest for day 7 blastocysts frozen in 3.6 M EG (98%) and
was not different from the control group (85%). The controlled freezing (0.3
degrees C/min to -35 degrees C) of expanded day 7 blastocysts resulted in a
hatching rate of 81%, which was similar to that of the nonfrozen controls (76%).
Differential staining revealed only very few degenerate blastomeres attributed to
freezing and thawing. Upon direct nonsurgical transfer of day 7 expanded
blastocysts frozen in 3.6 M EG, a pregnancy rate of 43% was achieved, while the
pregnancy rate after transfer of other developmental stages was significantly
lower (22% with expanded day 8 blastocysts). When bovine IVP embryos were
incubated at room temperature in 7.2 M EG preceded by preequilibration in 3.6 M
EG, the hatching rate of day 7 expanded blastocysts reached 93%. Upon
vitrification of IVP day 7 and day 8 blastocysts and expanded blastocysts in 7.2
M EG, the latter showed a higher hatching rate (42%) than blastocysts (12%).
Overall, PVA as supplement to the basic freezing solution instead of NBCS had
deleterious effects on survival after controlled freezing or vitrification. The
simple cryopreservation protocol employed in this study and the low toxicity of
ethylene glycol highlight the usefulness of this approach for controlled freezing
of IVP embryos. However, further experiments are needed to improve the pregnancy
rate following embryo transfer and to enhance survival after vitrification.
PMID- 10191035
TI - Sugars exert a major influence on the vitrification properties of ethylene glycol
based solutions and have low toxicity to embryos and oocytes.
AB - A systematic approach was taken to assess the vitrification properties of
ethylene glycol-based solutions supplemented with carbohydrates. Solutions were
prepared by weight (gravimetrically) using ethylene glycol as the cryoprotectant,
0.9% NaCl in water, and six different sugars: d-glucose, d(-)-fructose, d
sorbitol, sucrose, d(+)-trehalose, and raffinose. Sugars were added on a molal
basis (0. 1, 0.5, and 1 m). Characteristics of the solutions were measured during
warming by differential scanning calorimetry using a cooling rate of 100 degrees
C/min and a warming rate of 10 degrees C/min. In the absence of carbohydrates a
59 wt% EG-saline solution formed a stable glass. When EG was replaced by an
equimolal concentration of glucose, fructose, or sorbitol (monosaccharides) at
0.1, 0.5, or 1.0 m there was no change in the total solute concentration at which
vitrification occurred, but the glass transition (Tg) occurred at a higher
temperature than in EG-saline alone. When EG was replaced by an equimolal
concentration of sucrose or trehalose (disaccharides) both the Tg and the lowest
total solute concentration required for vitrification became progressively higher
as the molecular weight, or the ratio of sugar to EG in the solutions, increased.
At the highest tested disaccharide concentration (1 m) vitrification was achieved
at a total solute concentration of 65 wt% (sucrose) and 67 wt% (trehalose). The
polysaccharide raffinose significantly modified the vitrification properties of
ethylene glycol solutions. When 0.5 or 0.1 m raffinose replaced EG on an
equimolal basis the glass transition point was raised more than with either the
monosaccharides or the disaccharides. Raffinose allowed vitrification at a total
solute concentration of 67 wt% (0.5 m) and 63 wt% (0.1 m). The maturation of
immature mouse oocytes, and the development of embryos in media containing 5-7 mM
of any sugar was comparable to controls, indicating that they are not toxic.
Exposure of freshly collected GV or MII oocytes to sugar concentrations between
0.5 and 1.0 M, for up to 10 min had no significant effect on the proportion which
subsequently formed two cells. We conclude that added sugars do contribute to a
solutions overall vitrification properties, and their properties should be taken
into consideration when vitrification solutions are being designed or modified.
PMID- 10191034
TI - Expression of stress proteins, adhesion molecules, and interleukin-8 in
endothelial cells after preservation and reoxygenation.
AB - Endothelial activation is a central feature of preservation-induced allograft
injury. The present study aims at a quantitative assessment of stress proteins,
adhesion molecules, and interleukin-8 in a cell culture-based model of organ
preservation. Human umbilical vein endothelial cells were exposed to cold,
hypoxic storage in University of Wisconsin (UW), histidine-tryptophane
ketoglutarate (HTK), and EuroCollins solutions for 8 h with subsequent
rewarming/reoxygenation (rew/reox) for 1 and 4 h. A cell-based ELISA was designed
for detection of heat shock proteins (HSP) 60 and 70, intercellular adhesion
molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial
leukocyte adhesion molecule-1 (ELAM-1). Immunohistochemical staining was
performed for comparison. Interleukin-8 was quantified by ELISA. HSP 70 was
expressed after cold storage in HTK and EuroCollins solution and after rew/reox
in all groups. A constitutive expression of HSP 60 was observed with further
upregulation after rew/reox following cold storage in all experimental groups.
ICAM-1 was clearly upregulated, but VCAM-1 showed only weak expression after cold
storage and rew/reox. ELAM-1 was detectable in minimal amounts after cold storage
but was considerably upregulated after 4 h of rew/reox. A significant increase of
interleukin-8 release could be found after 4 h of rew/reox following storage in
EuroCollins solution. Expression of stress proteins can be considered as a new
parameter of preservation-associated endothelial activation. Apart from possible
protective effects, allograft vasculopathy could be in part a consequence of the
antigeneic potential of heat shock proteins connected with effects caused by
adhesion molecules and inflammatory cytokines.
PMID- 10191036
TI - Identification of a novel ice-nucleating bacterium of Antarctic origin and its
ice nucleation properties.
AB - A novel ice-nucleating bacterium (INB) was isolated from Ross Island, Antarctica.
INBs could be isolated more frequently than was generally thought. INB strain IN
74 was found in the white colony group. Strain IN-74 was identified from its
taxonomic characteristics as a novel INB, Pseudomonas antarctica IN-74. When
strain IN-74 was cultured aerobically in a medium consisting of the ice
nucleating broth (pH 7.0) for 6 days at 4 degrees C, the ice-nucleating activity
of strain IN-74 cells was obtained. Strain IN-74 cells produced ice nuclei only
at extremely low growth temperatures. The nuclei appeared to be less thermolabile
than those of INB Pseudomonas fluorescens KUIN-1. The freezing difference spectra
in D2O and H2O at ice-nucleating temperature for strain IN-74 cells and
conventional INBs (Pseudomonas fluorescens KUIN-1, Pseudomonas viridiflava KUIN
2, and Pseudomonas syringae C-9) exhibited different curves.
PMID- 10191037
TI - Cryobiophysical characteristics of genetically modified hematopoietic progenitor
cells.
AB - The freezing responses of hematopoietic progenitor cells isolated from normal
donors and from donors with mucopolysaccharidosis type I (MPS I) were determined
using cryomicroscopy and analyzed using theoretical models for water transport
and intracellular ice formation. The cells from donors with MPS I used in this
investigation were cultured and transduced with a retroviral vector for the alpha
l-iduronidase (IDUA) enzyme in preclinical studies for human gene therapy. The
water transport and intracellular ice formation (IIF) characteristics were
determined at different time points in the culture and transduction process for
hematopoietic progenitor cells expressing CD34 antigen from donors with MPS I and
from normal donors. There were statistically significant changes in water
transport, osmotically inactive cell volume fraction, and permeability between
cells from different sources (normal donors vs donors with MPSI) and different
culture conditions (freshly isolated vs cultured and transduced). Specifically,
Lpg and Ea increased after ex vivo culture of the cells and the changes in
permeability parameters were observed after as little as 3 days in culture.
Similarly, the IIF characteristics of hematopoietic progenitor cells can also be
influenced by the culture and transduction process. The IIF characteristics of
freshly isolated cells from donors with MPS I were statistically distinct from
those of cultured and transduced cells from the same donor. The ability to
cryopreserve cells which are cultured ex vivo for therapeutic purposes will
require an understanding of the biophysical changes resulting from the culture
conditions and the manner in which these changes influence viability.
PMID- 10191039
TI - Vitrification of two-cell rat embryos derived from immature hypothyroid rdw rats
by in vitro fertilization in ethylene glycol-based solutions.
AB - Two-cell embryos derived from immature rdw rats by in vitro fertilization (IVF)
were vitrified in ethylene glycol-based solutions. Embryos exposed to EFS20
before being vitrified in EFS40 exhibited improved viability in vitro. All
embryos exposed to EFS20 for 1-3 min before vitrification in EFS40 were
morphologically normal. However, 2-3 min of exposure to EFS20 increased the
number of embryos that developed beyond the four-cell stage. More embryos exposed
to EFS20 for 2-3 min developed to morulae (63-64%) and blastocysts (34-38%) than
those exposed for 1 min (35 and 10%, respectively). After transfer, 33% of
embryos exposed to EFS20 for 3 min and vitrified in EFS40 developed to term
compared to 29% of fresh embryos. Fifteen (47%) of live young were homozygous rdw
and all of the others were heterozygous rats. The present study demonstrated that
vitrification in EFS solution can be routinely used to cryopreserve rat two-cell
IVF-embryos with no loss of viability.
PMID- 10191038
TI - Cryopreservation of rat and human liver slices by rapid freezing.
AB - The cryopreservation of human liver slices is a promising way to enhance the
ability to test the metabolism of drug candidates. This study demonstrates the
use of a novel technique for the cryopreservation of both rat and human liver
slices. In this technique the slices are treated with Me2SO and sandwiched
between aluminum plates separated by a thin gasket. The device is then submerged
in liquid nitrogen to freeze the slices, which can then be stored until use. To
thaw the slices, the apparatus is submerged in a water bath at 37 degrees C.
Slices frozen and thawed in this manner were compared to those frozen in
conventional cryovials. The viability of the slices was determined by incubating
them in 12-well plates and measuring urea synthesis, ethoxycoumarin metabolism,
and cytosolic enzyme leakage (LDH and ALT). The viability of rat slices frozen
between plates approached that of fresh slices and was consistently higher than
slices frozen in cryovials. Slices from two human samples gave similar results.
The technique was found to work over a wide range of Me2SO concentrations (4.5 to
22% was tested) with an optimal concentration between 10 and 15%.
PMID- 10191040
TI - Isolation of human hepatocytes after hepatic warm and cold ischemia: a practical
approach using University of Wisconsin solution.
AB - A method is described for isolating human hepatocytes from tissue fragments after
warm and cold ischemia as experienced during hepatic resections. Cells with a
high trypan blue dye exclusion and good culture characteristics were isolated by
employing an initial tissue perfusion with UW solution. The method could
facilitate transfer of liver tissues between distant centers for cell isolation
studies.
PMID- 10191042
TI - Nigel holder (July 2, 1953-december 11, 1998)
PMID- 10191041
TI - An in vivo study of antifreeze protein adjuvant cryosurgery.
AB - Cryosurgery employs freezing to destroy undesirable tissue. However, under
certain thermal conditions, frozen tissues survive. The survival of frozen
undesirable tissue may lead to complications, such as recurrence of cancer. In a
study of nude mice with subcutaneous metastatic prostate tumors, we showed that
the preoperative injection of a phosphate-buffered saline solution with 10 mg/ml
antifreeze protein of type I into the tumor prior to freezing enhances
destruction under thermal conditions which normally yield cell survival. This
suggests that the adjunctive use of antifreeze proteins in cryosurgery may reduce
the complications from undesirable tissues that survive freezing.
PMID- 10191043
TI - Microsatellite loci in wild-type and inbred Strongylocentrotus purpuratus.
AB - Strongylocentrotus purpuratus, a major research model in developmental molecular
biology, has been inbred through six generations of sibling matings. Though
viability initially decreased, as described earlier, the inbred line now consists
of healthy, fertile animals. These are intended to serve as a genomic resource in
which the level of polymorphism is decreased with respect to wild S. purpuratus.
To genotype the inbred animals eight simple sequence genomic repeats were
isolated, in context, and PCR primers were generated against the flanking single
copy sequences. Distribution and polymorphism of these regions of the genome were
studied in the genomes of 27 wild individuals and in a sample of the inbred
animals at F2 and F3 generations. All eight regions were polymorphic, though to
different extents, and their homozygosity was increased by inbreeding as
expected. The eight markers suffice to identify unambiguously the cellular DNA of
any wild or F3 S. purpuratus individual.
PMID- 10191044
TI - ELT-3: A Caenorhabditis elegans GATA factor expressed in the embryonic epidermis
during morphogenesis.
AB - We have identified a gene encoding a new member of the Caenorhabditis elegans
GATA transcription factor family, elt-3. The predicted ELT-3 polypeptide contains
a single GATA-type zinc finger (C-X2-C-X17-C-X2-C) along with a conserved
adjacent basic region. elt-3 mRNA is present in all stages of C. elegans
development but is most abundant in embryos. Reporter gene analysis and antibody
staining show that elt-3 is first expressed in the dorsal and ventral hypodermal
cells, and in hypodermal cells of the head and tail, immediately after the final
embryonic cell division that gives rise to these cells. No expression is seen in
the lateral hypodermal (seam) cells. elt-3 expression is maintained at a constant
level in the epidermis until the 2(1/2)-fold stage of development, after which
reporter gene expression declines to a low level and endogenous protein can no
longer be detected by specific antibody. A second phase of elt-3 expression in
cells immediately anterior and posterior to the gut begins in pretzel-stage
embryos. elt-1 and lin-26 are two genes known to be important in specification
and maintenance of hypodermal cell fates. We have found that elt-1 is required
for the formation of most, but not all, elt-3-expressing cells. In contrast, lin
26 function does not appear necessary for elt-3 expression. Finally, we have
characterised the candidate homologue of elt-3 in the nematode Caenorhabditis
briggsae. Many features of the elt-3 genomic and transcript structure are
conserved between the two species, suggesting that elt-3 is likely to perform an
evolutionarily significant function during development.
PMID- 10191045
TI - Z/AP, a double reporter for cre-mediated recombination.
AB - The Cre/loxP site-specific recombination system combined with embryonic stem cell
mediated technologies has greatly expanded our capability to address normal and
disease development in mammals using genetic approaches. The success of this
emerging technology hinges on the production of Cre-expressing transgenic lines
that provide cell type-, tissue-, or developmental stage-specific recombination
between loxP sites placed in the genome. Here we describe and characterize the
production of a double-reporter mouse line that provides a convenient and
reliable readout of Cre recombinase activity. Throughout all embryonic and adult
stages, the transgenic animal expresses the lacZ reporter gene before Cre
mediated excision occurs. Cre excision, however, removes the lacZ gene, allowing
expression of the second reporter, the human alkaline phosphatase gene. This
double-reporter transgenic line is able to indicate the occurrence of Cre
excision in an extremely widespread manner from early embryonic to adult
lineages. It will be a valuable reagent for the increasing number of
investigators taking advantage of the powerful tools provided by the Cre/loxP
site-specific recombinase system.
PMID- 10191046
TI - Murine fibroblast growth factor receptor 1alpha isoforms mediate node regression
and are essential for posterior mesoderm development.
AB - Alternative splicing in the fibroblast growth factor receptor 1 (Fgfr1) locus
generates a variety of splicing isoforms, including FGFR1alpha isoforms, which
contain three immunoglobulin-like loops in the extracellular domain of the
receptor. It has been previously shown that embryos carrying targeted disruptions
of all major isoforms die during gastrulation, displaying severe growth
retardation and defective mesodermal structures. Here we selectively disrupted
the FGFR1alpha isoforms and found that they play an essential role in posterior
mesoderm formation during gastrulation. We show that the mutant embryos lack
caudal somites, develop spina bifida, and die at 9.5-12.5 days of embryonic
development because they are unable to establish embryonic circulation. The
primary defect is a failure of axial mesoderm cell migration toward the posterior
portions of the embryos during gastrulation, as revealed by regional marker
analysis and DiI labeling. In contrast, the anterior migration of the notochord
is unaffected and the embryonic structures rostral to the forelimb are relatively
normal. These data demonstrate that FGF/FGFR1alpha signals are posteriorizing
factors that control node regression and posterior embryonic development.
PMID- 10191047
TI - Connexin 43 expression reflects neural crest patterns during cardiovascular
development.
AB - We used transgenic mice in which the promoter sequence for connexin 43 linked to
a lacZ reporter was expressed in neural crest but not myocardial cells to
document the pattern of cardiac neural crest cells in the caudal pharyngeal
arches and cardiac outflow tract. Expression of lacZ was strikingly similar to
that of cardiac neural crest cells in quail-chick chimeras. By using this
transgenic mouse line to compare cardiac neural crest involvement in cardiac
outflow septation and aortic arch artery development in mouse and chick, we were
able to note differences and similarities in their cardiovascular development.
Similar to neural crest cells in the chick, lacZ-positive cells formed a sheath
around the persisting aortic arch arteries, comprised the aorticopulmonary
septation complex, were located at the site of final fusion of the conal
cushions, and populated the cardiac ganglia. In quail-chick chimeras generated
for this study, neural crest cells entered the outflow tract by two pathways,
submyocardially and subendocardially. In the mouse only the subendocardial
population of lacZ-positive cells could be seen as the cells entered the outflow
tract. In addition lacZ-positive cells completely surrounded the aortic sac prior
to septation, while in the chick, neural crest cells were scattered around the
aortic sac with the bulk of cells distributed in the bridging portion of the
aorticopulmonary septation complex. In the chick, submyocardial populations of
neural crest cells assembled on opposite sides of the aortic sac and entered the
conotruncal ridges. Even though the aortic sac in the mouse was initially
surrounded by lacZ-positive cells, the two outflow vessels that resulted from its
septation showed differential lacZ expression. The ascending aorta was invested
by lacZ-positive cells while the pulmonary trunk was devoid of lacZ staining. In
the chick, both of these vessels were invested by neural crest cells, but the
cells arrived secondarily by displacement from the aortic arch arteries during
vessel elongation. This may indicate a difference in derivation of the pulmonary
trunk in the mouse or a difference in distribution of cardiac neural crest cells.
An independent mouse neural crest marker is needed to confirm whether the
differences are indeed due to species differences in cardiovascular and/or neural
crest development. Nevertheless, with the differences noted, we believe that this
mouse model faithfully represents the location of cardiac neural crest cells. The
similarities in location of lacZ-expressing cells in the mouse to that of cardiac
neural crest cells in the chick suggest that this mouse is a good model for
studying mammalian cardiac neural crest and that the mammalian cardiac neural
crest performs functions similar to those shown for chick.
PMID- 10191048
TI - Independent development of sensory and motor innervation patterns in embryonic
chick hindlimbs.
AB - Previous studies suggest that sensory axon outgrowth is guided by motoneurons,
which are specified to innervate particular target muscles. Here we present
evidence that questions this conclusion. We have used a new approach to assess
the pathfinding abilities of bona fide sensory neurons, first by eliminating
motoneurons after neural crest cells have coalesced into dorsal root ganglia
(DRG) and second by challenging sensory neurons to innervate muscles in a novel
environment created by shifting a limb bud rostrally. The resulting sensory
innervation patterns mapped with the lipophilic dyes DiI and DiA showed that
sensory axons projected robustly to muscles in the absence of motoneurons, if
motoneurons were eliminated after DRG formation. Moreover, sensory neurons
projected appropriately to their usual target muscles under these conditions. In
contrast, following limb shifts, muscle sensory innervation was often derived
from inappropriate segments. In this novel environment, sensory neurons tended to
make more "mistakes" than motoneurons. Whereas motoneurons tended to innervate
their embryologically correct muscles, sensory innervation was more widespread
and was generally from more rostral segments than normal. Similar results were
obtained when motoneurons were eliminated in embryos with limb shifts. These
findings show that sensory neurons are capable of navigating through their usual
terrain without guidance from motor axons. However, unlike motor axons, sensory
axons do not appear to actively seek out appropriate target muscles when
confronted with a novel terrain. These findings suggest that sensory neuron
identity with regard to pathway and target choice may be unspecified or quite
plastic at the time of initial axon outgrowth.
PMID- 10191049
TI - Control of oocyte maturation in sexually mature Drosophila females.
AB - In many sexually mature insects egg production and oviposition are tightly
coupled to copulation. Sex-Peptide is a 36-amino-acid peptide synthesized in the
accessory glands of Drosophila melanogaster males and transferred to the female
during copulation. Sex-Peptide stimulates vitellogenic oocyte progression through
a putative control point at about stage 9 of oogenesis. Here we show that
application of the juvenile hormone analogue methoprene mimics the Sex-Peptide
mediated stimulation of vitellogenic oocyte progression in sexually mature virgin
females. Apoptosis is induced by 20-hydroxyecdysone in nurse cells of stage 9 egg
chambers at physiological concentrations (10(-7) M). 20-Hydroxyecdysone thus acts
as an antagonist of early vitellogenic oocyte development. Simultaneous
application of juvenile hormone analogue, however, protects early vitellogenic
oocytes from 20-hydroxyecdysone-induced resorption. These results suggest that
the balance of these hormones in the hemolymph regulates whether oocytes will
progress through the control point at stage 9 or undergo apoptosis. These data
are further supported by a molecular analysis of the regulation of yolk protein
synthesis and uptake into the ovary by the two hormones. We conclude that
juvenile hormone is a downstream component in the Sex-Peptide response cascade
and acts by stimulating vitellogenic oocyte progression and inhibiting apoptosis.
Since juvenile hormone analogue does not elicit increased oviposition and reduced
receptivity, Sex-Peptide must have an additional, separate effect on these two
postmating responses.
PMID- 10191050
TI - Opposite effects of FGF and BMP-4 on embryonic blood formation: roles of PV.1 and
GATA-2.
AB - In adult vertebrates, fibroblast growth factor (FGF) synergizes with many
hematopoietic cytokines to stimulate the proliferation of hematopoietic
progenitors. In vertebrate development, the FGF signaling pathway is important in
the formation of some derivatives of ventroposterior mesoderm. However, the
function of FGF in the specification of the embryonic erythropoietic lineage has
remained unclear. Here we address the role of FGF in the specification of the
erythropoietic lineage in the Xenopus embryo. We report that ventral injection of
embryonic FGF (eFGF) mRNA at as little as 10 pg at the four-cell stage suppresses
ventral blood island (VBI) formation, whereas expression of the dominant negative
form of the FGF receptor in the lateral mesoderm, where physiologically no blood
tissue is formed, results in a dramatic expansion of the VBI. Similar results
were observed in isolated ventral marginal zones and animal caps. Bone
morphogenetic protein-4 (BMP-4) is known to induce erythropoiesis in the Xenopus
embryo. Therefore, we examined how the BMP-4 and FGF signaling pathways might
interact in the decision of ventral mesoderm to form blood. We observed that eFGF
inhibits BMP-4-induced erythropoiesis by differentially regulating expression of
the BMP-4 downstream effectors GATA-2 and PV.1. GATA-2, which stimulates
erythropoiesis, is suppressed by FGF. PV.1, which we demonstrate to inhibit blood
development, is enhanced by FGF. Additionally, PV.1 and GATA-2 negatively
regulate transcription of each other. Thus, BMP-4 induces two transcription
factors which have opposing effects on blood development. The FGF and BMP-4
signaling pathways interact to regulate the specification of the erythropoietic
lineage.
PMID- 10191051
TI - Association between mouse nude gene expression and the initiation of epithelial
terminal differentiation.
AB - Loss-of-function mutations in Whn (Hfh 11), a winged-helix/forkhead transcription
factor, result in the nude mouse phenotype. To determine the whn expression
pattern during development, we utilized mice in which a beta-galactosidase
reporter gene was placed under the control of the wild-type whn promoter by
homologous recombination (M. Nehls et al., 1996, Science 272, 886-889). Sites of
reporter expression were confirmed by immunohistochemical staining for Whn
protein or by in situ hybridization for whn mRNA. At all developmental stages,
whn expression is restricted to epithelial cells. In addition to the skin and
thymus, whn is expressed in the developing nails, nasal passages, tongue, palate,
and teeth. In embryonic epidermis, suprabasal cells induce whn expression at the
same time that terminal differentiation markers first appear. As the epidermis
matures, whn promoter activity is found primarily in the first suprabasal layer,
which contains keratinocytes in the early stages of terminal differentiation. In
developing and mature anagen hair follicles, whn is expressed at high levels in
the postmitotic precursor cells of the hair shaft and inner root sheath. Though
principally associated with terminal differentiation, whn expression is also
detected in progenitor cell compartments; in the hair bulb matrix and basal
epidermal layer, a small subclass of cells expresses whn, while in the outer root
sheath, whn promoter activity is induced as the follicle completes its
elongation. Within these compartments, rare cells exhibit both whn expression and
the nuclear proliferation marker Ki-67. The results suggest that whn expression
encompasses the transition from a proliferative to a postmitotic state and that
whn regulates the initiation of terminal differentiation.
PMID- 10191052
TI - Retinoid signaling is required for chondrocyte maturation and endochondral bone
formation during limb skeletogenesis.
AB - Retinoids have long been known to influence skeletogenesis but the specific roles
played by these effectors and their nuclear receptors remain unclear. Thus, it is
not known whether endogenous retinoids are present in developing skeletal
elements, whether expression of the retinoic acid receptor (RAR) genes alpha,
beta, and gamma changes during chondrocyte maturation, or how interference with
retinoid signaling affects skeletogenesis. We found that immature chondrocytes
present in stage 27 (Day 5.5) chick embryo humerus exhibited low and diffuse
expression of RARalpha and gamma, while RARbeta expression was strong in
perichondrium. Emergence of hypertrophic chondrocytes in Day 8-10 embryo limbs
was accompanied by a marked and selective up-regulation of RARgamma gene
expression. The RARgamma-rich type X collagen-expressing hypertrophic
chondrocytes lay below metaphyseal prehypertrophic chondrocytes expressing Indian
hedgehog (Ihh) and were followed by mineralizing chondrocytes undergoing
endochondral ossification. Bioassays revealed that cartilaginous elements in Day
5.5, 8.5, and 10 chick embryo limbs all contained endogenous retinoids;
strikingly, the perichondrial tissues surrounding the cartilages contained very
large amounts of retinoids. Implantation of beads filled with retinoid antagonist
Ro 41-5253 or AGN 193109 near the humeral anlagens in stage 21 (Day 3.5) or stage
27 chick embryos severely affected humerus development. In comparison to their
normal counterparts, antagonist-treated humeri in Day 8.5-10 chick embryos were
significantly shorter and abnormally bent; their diaphyseal chondrocytes had
remained prehypertrophic Ihh-expressing cells, did not express RARgamma, and were
not undergoing endochondral ossification. Interestingly, formation of an
intramembranous bony collar around the diaphysis was not affected by antagonist
treatment. Using chondrocyte cultures, we found that the antagonists effectively
interfered with the ability of all-trans-retinoic acid to induce terminal cell
maturation. The results provide clear evidence that retinoid-dependent and RAR
mediated mechanisms are required for completion of the chondrocyte maturation
process and endochondral ossification in the developing limb. These mechanisms
may be positively influenced by cooperative interactions between the chondrocytes
and their retinoid-rich perichondrial tissues.
PMID- 10191053
TI - Intracellular pH regulation by HCO3-/Cl- exchange is activated during early mouse
zygote development.
AB - We report here that at least one major pHi-regulatory mechanism, the HCO3-/Cl-
exchanger, is quiescent in unfertilized mouse eggs but becomes fully activated
during early development following fertilization. Zygotes (8-12 h
postfertilization) exhibited a marked intracellular alkalinization upon external
Cl- removal, which is indicative of active HCO3-/Cl- exchangers, in contrast to
the very small response observed in eggs. In addition, efflux of Cl- from eggs
upon external Cl- removal was much slower than that from zygotes, indicating
additional pathways for Cl- to cross the plasma membrane in zygotes. Furthermore,
while zygotes quickly recovered from an induced alkalosis, eggs exhibited only a
slow, incomplete recovery. Following in vitro fertilization (IVF), increased HCO3
/Cl- exchanger activity was first detectable about 4 h postfertilization and
reached the maximal level after about 8 h. The upregulation of HCO3-/Cl-
exchanger activity after fertilization appeared to occur by activation of
existing, inactive exchangers rather than by synthesis or transport of new
exchangers, as the increase in activity following IVF was unaffected by
inhibition of protein synthesis or by disruption of the Golgi apparatus or the
cytoskeleton. This activation may depend on the Ca2+ transients which follow
fertilization, as suppression of these transients, using the Ca2+ chelator BAPTA,
reduced subsequent upregulation of HCO3-/Cl- exchanger activity by about 50%.
Activation of pHi-regulatory systems may be a widespread feature of the earliest
period of embryonic development, not restricted to species such as marine
invertebrates as previously believed.
PMID- 10191054
TI - Notchspl is deficient for inductive processes in the eye, and E(spl)D enhances
split by interfering with proneural activity.
AB - Eye development in Drosophila involves the Notch signaling pathway at several
consecutive steps. At first, Notch signaling is required for stable expression of
the proneural gene atonal (ato), thereby maintaining neural potential of the
cells. Second, in a process of lateral inhibition, Notch signaling is necessary
to confine neural commitment to individual photoreceptor founder cells. Later on,
the successive addition of cells to maturing ommatidia is under Notch control. In
contrast to previous assumptions, the recessive Notch allele split (Nspl)
involves specifically loss of the early proneural Notch activity in the eye,
which is in agreement with bristle defects as well. As a result, fewer cells gain
neural potential and fewer ommatidia are founded. Enhancement of this phenotype
by the dominant mutation Enhancer of split [E(spl)D] happens within the remaining
proneural cells, in which Ato expression is abolished. In line with genetic data,
this process occurs primarily at the protein level due to altered protein-protein
interactions between the aberrant E(spl)D and proneural proteins. Nspl is the
first Notch mutation known to specifically affect Notch inductive processes
during eye development.
PMID- 10191055
TI - Mound-cell movement and morphogenesis in Dictyostelium.
AB - To examine the mechanisms of cell locomotion within a three-dimensional (3-D)
cell mass, we have undertaken a systematic 3-D analysis of individual cell
movements in the Dictyostelium mound, the first 3-D structure to form during
development of the fruiting body. We used time-lapse deconvolution microscopy to
examine two strains whose motion represents endpoints on the spectrum of motile
behaviors that we have observed in mounds. In AX-2 mounds, cell motion is slow
and trajectories are a combination of random and radial, compared to KAX-3, in
which motion is fivefold faster and most trajectories are rotational. Although
radial or rotational motion was correlated with the optical-density wave patterns
present in each strain, we also found small but significant subpopulations of
cells that moved differently from the majority, demonstrating that optical
density waves are at best insufficient to explain all motile behavior in mounds.
In examining morphogenesis in these strains, we noted that AX-2 mounds tended to
culminate directly to a fruiting body, whereas KAX-3 mounds first formed a
migratory slug. By altering buffering conditions we could interchange these
behaviors and then found that mound-cell motions also changed accordingly. This
demonstrates a correlation between mound-cell motion and subsequent development,
but it is not obligatory. Chimeric mounds composed of only 10% KAX-3 cells and
90% AX-2 cells exhibited rotational motion, suggesting that a diffusible molecule
induces rotation, but many of these mounds still culminated directly,
demonstrating that rotational motion does not always lead to slug migration. Our
observations provide a detailed analysis of cell motion for two distinct modes of
mound and slug formation in Dictyostelium.
PMID- 10191056
TI - Thalamocortical axons are influenced by chemorepellent and chemoattractant
activities localized to decision points along their path.
AB - Thalamocortical axons (TCAs), which originate in dorsal thalamus, project
ventrally in diencephalon and then dorsolaterally in ventral telencephalon to
their target, the neocortex. To elucidate potentially key decision points in TCA
pathfinding and hence the possible localization of guidance cues, we used DiI
tracing to describe the initial trajectory of TCAs in mice. DiI-labeled TCAs
extend ventrally on the lateral surface of ventral thalamus. Rather than
continuing this trajectory onto the lateral surface of the hypothalamus, TCAs
make a sharp lateral turn into ventral telencephalon. This behavior suggests that
the hypothalamus is repulsive and the ventral telencephalon attractive for TCAs.
In support of this hypothesis, we find that axon outgrowth from explants of
dorsal thalamus is biased away from hypothalamus and toward ventral telencephalon
when cocultured at a distance in collagen gels. The in vivo DiI analysis also
reveals a broad cluster of retrogradely labeled neurons in the medial part of
ventral telencephalon positioned within or adjacent to the thalamocortical
pathway prior to or at the time TCAs are extending through it. The axons of these
neurons extend into or through dorsal thalamus and appear to be coincident with
the oppositely extending TCAs. These findings suggest that multiple cues guide
TCAs along their pathway from dorsal thalamus to neocortex: TCAs may fasciculate
on the axons of ventral telencephalic neurons as they extend through ventral
thalamus and the medial part of ventral telencephalon, and chemorepellent and
chemoattractant activities expressed by hypothalamus and ventral telencephalon,
respectively, may cooperate to promote the turning of TCAs away from hypothalamus
and into ventral telencephalon.
PMID- 10191057
TI - Neural crest can form cartilages normally derived from mesoderm during
development of the avian head skeleton.
AB - The lateral wall of the avian braincase, which is indicative of the primitive
amniote condition, is formed from mesoderm. In contrast, mammals have replaced
this portion of their head skeleton with a nonhomologous bone of neural crest
origin. Features that characterize the local developmental environment may have
enabled a neural crest-derived skeletal element to be integrated into a
mesodermal region of the braincase during the course of evolution. The lateral
wall of the braincase lies along a boundary in the head that separates neural
crest from mesoderm, and also, neural crest cells migrate through this region on
their way to the first visceral arch. Differences in the availability of one
skeletogenic population versus the other may determine the final composition of
the lateral wall of the braincase. Using the quail-chick chimeric system, this
investigation tests if populations of neural crest, when augmented and expanded
within populations of mesoderm, will give rise to the lateral wall of the
braincase. Results demonstrate that neural crest can produce cartilages that are
morphologically indistinguishable from elements normally generated by mesoderm.
These findings (1) indicate that neural crest can respond to the same cues that
both promote skeletogenesis and enable proper patterning in mesoderm, (2)
challenge hypotheses on the nature of the boundary between neural crest and
mesoderm in the head, and (3) suggest that changes in the allocation of migrating
cells could have enabled a neural crest-derived skeletal element to replace a
mesodermal portion of the braincase during evolution.
PMID- 10191058
TI - Two structural variants of Nek2 kinase, termed Nek2A and Nek2B, are
differentially expressed in Xenopus tissues and development.
AB - Nek2 kinase, a NIMA-related kinase, has been suggested to play both meiotic and
mitotic roles in mammals, but its function(s) during development is poorly
understood. We have isolated here cDNAs encoding a Xenopus homolog of mammalian
Nek2 and have shown that Xenopus Nek2 has two structural variants, termed Nek2A
and Nek2B. Nek2A, most likely a C-terminally spliced form, corresponds to the
previously described human and mouse Nek2, while Nek2B is most probably a novel,
C-terminally unspliced form of Nek2. As a consequence of this (probable)
alternative splicing, Nek2B lacks the C-terminal 70-amino-acid sequence of Nek2A,
which contains a PEST sequence (or a motif for rapid degradation). Western blot
analysis reveals that Nek2A is expressed predominantly in the testis (presumably
in spermatocytes) and very weakly in the stomach and, during development, only
after the neurula stage. By contrast, Nek2B is expressed mainly in the ovary and
in both primary and secondary oocytes and early embryos up to the neurula stage.
These results suggest that Nek2A and Nek2B may play both meiotic and mitotic
roles, but in a spatially and temporally complementary manner during Xenopus
development, and that Nek2B, rather than Nek2A (or the conventional form of
Nek2), may play an important role in early development. We discuss the
possibility that a counterpart of Xenopus Nek2B might also exist and function in
early mammalian development.
PMID- 10191059
TI - Evolutionary conservation of MyoD function and differential utilization of E
proteins.
AB - The formation of striated muscle in both vertebrates and invertebrates involves
the activity of the MyoD family of basic-helix-loop-helix (bHLH) transcription
factors. The high degree of evolutionary conservation of MyoD-related proteins,
both in the sequence of their bHLH domains and in their general developmental
expression patterns, suggests that these factors are also conserved at the level
of function. We have addressed this directly using MyoD and E protein factors
from vertebrates, Drosophila, and Caenorhabditis elegans. Various MyoD and E
factor combinations were tested for their ability to interact in vitro and to
function in vivo in the myogenic conversion of 10T12 mouse fibroblasts. We found
that the ability of different homo- and heterodimers to bind DNA in vitro was an
accurate measure of biological activity in vivo. A second assessment of conserved
function comes from the ability of these factors to rescue a C. elegans hlh-1
(CeMyoD) null mutation. We found that both Drosophila and chicken MyoD-related
factors were able to rescue a C. elegans CeMyoD loss-of-function mutation. These
results demonstrate a remarkable degree of functional conservation of these
myogenic factors despite differences in E-protein interactions.
PMID- 10191060
TI - Mutations in the zebrafish unmask shared regulatory pathways controlling the
development of catecholaminergic neurons.
AB - The mechanism by which pluripotent progenitors give rise to distinct classes of
mature neurons in vertebrates is not well understood. To address this issue we
undertook a genetic screen for mutations which affect the commitment and
differentiation of catecholaminergic (CA) [dopaminergic (DA), noradrenergic (NA),
and adrenergic] neurons in the zebrafish, Danio rerio. The identified mutations
constitute five complementation groups. motionless and foggy affect the number
and differentiation state of hypothalamic DA, telencephalic DA, retinal DA, locus
coeruleus (LC) NA, and sympathetic NA neurons. The too few mutation leads to a
specific reduction in the number of hypothalamic DA neurons. no soul lacks arch
associated NA cells and has defects in pharyngeal arches, and soulless lacks both
arch-associated and LC cell groups. Our analyses suggest that the genes defined
by these mutations regulate different steps in the differentiation of multipotent
CA progenitors. They further reveal an underlying universal mechanism for the
control of CA cell fates, which involve combinatorial usage of regulatory genes.
PMID- 10191061
TI - Zonula occludens-1 and E-cadherin are coordinately expressed in the mouse uterus
with the initiation of implantation and decidualization.
AB - Two-way interactions between the blastocyst trophectoderm and the uterine luminal
epithelium are essential for implantation. The key events of this process are
cell-cell contact of trophectoderm cells with uterine luminal epithelial cells,
controlled invasion of trophoblast cells through the luminal epithelium and the
basement membrane, transformation of uterine stromal cells surrounding the
blastocyst into decidual cells, and protection of the "semiallogenic" embryo from
the mother's immunological responses. Because cell-cell contact between the
trophectoderm epithelium and the luminal epithelium is essential for
implantation, we investigated the expression of zonula occludens-1 (ZO-1) and E
cadherin, two molecules associated with epithelial cell junctions, in the mouse
uterus during the periimplantation period. Preimplantation uterine epithelial
cells express both ZO-1 and E-cadherin. With the initiation and progression of
implantation, ZO-1 and E-cadherin are expressed in stromal cells of the primary
decidual zone (PDZ). As trophoblast invasion progresses, these two molecules are
expressed in stroma in advance of the invading trophoblast cells. These results
suggest that expression of these adherence and tight junctions molecules in the
PDZ serves to function as a permeability barrier to regulate access of
immunologically competent maternal cells and/or molecules to the embryo and
provide homotypic guidance of trophoblast cells in the endometrium.
PMID- 10191062
TI - Multiple mechanisms contribute to the avoidance of avian epidermis by sensory
axons.
AB - In birds, sensory innervation of skin is restricted to dermis, with few axons
penetrating into the epidermis. This pattern of innervation is maintained in
vitro, where sensory neurites avoid explants of epidermis but grow readily on
dermis. We have used this coculture paradigm to investigate the mechanisms that
impede innervation of avian epidermis. The lack of epidermal innervation in birds
has been attributed to diffusible chondroitin sulfate proteoglycans (CSPGs)
secreted by the epidermis, although direct experimental evidence is weak. We
found that elimination of CSPG function with either chondroitinase or
neutralizing antibodies did not promote growth of DRG neurites onto epidermis in
vitro, indicating that CSPGs alone are not responsible for preventing epidermal
innervation. Moreover, the failure of sensory neurites to invade epidermis is not
due exclusively to soluble chemorepulsive factors, since sensory neurites also
avoid dead epidermis. This inhibition can be overridden, however, by coating
epidermis with the growth-promoting molecule laminin, but only if the tissue is
killed first. Epidermal innervation of laminin-coated epidermis is even more
robust when CSPGs are also eliminated. Thus, the absence of growth-promoting or
permissive molecules, such as laminin, may contribute to the failure of sensory
neurites to invade avian epidermis. Together these results show that the
inhibitory character of avian epidermis is complex. Cell- or matrix-associated
CSPGs clearly contribute to the inhibition, but are not solely responsible.
PMID- 10191063
TI - Requirement for the Xrcc1 DNA base excision repair gene during early mouse
development.
AB - Surveillance and repair of DNA damage are essential for maintaining the integrity
of the genetic information that is needed for normal development. Several
multienzyme pathways, including the excision repair of damaged or missing bases,
carry out DNA repair in mammals. We determined the developmental role of the X
ray cross-complementing (Xrcc)-1 gene, which is central to base excision repair,
by generating a targeted mutation in mice. Heterozygous matings produced Xrcc1-/-
embryos at early developmental stages, but not Xrcc1-/- late-stage fetuses or
pups. Histology showed that mutant (Xrcc1-/-) embryos arrested at embryonic day
(E) 6.5 and by E7.5 were morphologically abnormal. The most severe abnormalities
observed in mutant embryos were in embryonic tissues, which showed increased cell
death in the epiblast and an altered morphology in the visceral embryonic
endoderm. Extraembryonic tissues appeared relatively normal at E6.5-7.5. Even
without exposure to DNA-damaging agents, mutant embryos showed increased levels
of unrepaired DNA strand breaks in the egg cylinder compared with normal embryos.
Xrcc1-/- cell lines derived from mutant embryos were hypersensitive to mutagen
induced DNA damage. Xrcc1 mutant embryos that were also made homozygous for a
null mutation in Trp53 underwent developmental arrest after only slightly further
development, thus revealing a Trp53-independent mechanism of embryo lethality.
These results show that an intact base excision repair pathway is essential for
normal early postimplantation mouse development and implicate an endogenous
source of DNA damage in the lethal phenotype of embryos lacking this repair
capacity.
PMID- 10191064
TI - TGFbeta2 and TGFbeta3 have separate and sequential activities during epithelial
mesenchymal cell transformation in the embryonic heart.
AB - Heart valve formation is initiated by an epithelial-mesenchymal cell
transformation (EMT) of endothelial cells in the atrioventricular (AV) canal.
Mesenchymal cells formed from cardiac EMTs are the initial cellular components of
the cardiac cushions and progenitors of valvular and septal fibroblasts. It has
been shown that transforming growth factor beta (TGFbeta) mediates EMT in the AV
canal, and TGFbeta1 and 2 isoforms are expressed in the mouse heart while TGFbeta
2 and 3 are expressed in the avian heart. Depletion of TGFbeta3 in avian or
TGFbeta2 in mouse leads to developmental defects of heart tissue. These
observations raise questions as to whether multiple TGFbeta isoforms participate
in valve formation. In this study, we examined the localization and function of
TGFbeta2 and TGFbeta3 in the chick heart during EMT. TGFbeta2 was present in both
endothelium and myocardium before and after EMT. TGFbeta2 antibody inhibited
endothelial cell-cell separation. In contrast, TGFbeta3 was present only in the
myocardium before EMT and was in the endothelium at the initiation of EMT.
TGFbeta3 antibodies inhibited mesenchymal cell formation and migration into the
underlying matrix. Both TGFbeta2 and 3 increased fibrillin 2 expression. However,
only TGFbeta2 treatment increased cell surface beta-1,4-galactosyltransferase
expression. These data suggest that TGFbeta2 and TGFbeta3 are sequentially and
separately involved in the process of EMT. TGFbeta2 mediates initial endothelial
cell-cell separation while TGFbeta3 is required for the cell morphological change
that enables the migration of cells into the underlying ECM.
PMID- 10191065
TI - Colonization history of atlantic island common chaffinches (Fringilla coelebs)
revealed by mitochondrial DNA.
AB - Common chaffinches (Fringilla coelebs) are thought to have colonized the Atlantic
island archipelagoes (the Azores, Madeira, and the Canaries) from neighboring
continental populations (Iberia and north Africa) within the last million years.
However, colonization may have occurred separately from north Africa to the
Canaries and from Iberia to the Azores (as would be predicted geographically) or
in one wave from Iberia to the Azores and then to Madeira and the Canaries. These
alternatives have different implications for the evolution of morphometric and
plumage differentiation in island chaffinches. To determine the most likely
colonization route, we estimated the phylogenetic relationships among island and
continental subspecies of common chaffinch using sequences from four mtDNA genes
(cytochrome b, ATPase 6, NADH 5, and the control region). The most strongly
supported mtDNA phylogeny places the continental subspecies together as the
sister group to a monophyletic clade containing the island subspecies. This is
consistent with a single wave of colonization, and suggests that patterns of
similarity among Atlantic island common chaffinches, such as blue pigmentation,
short wings, and long tarsi, are due to common colonization history rather than
to convergent evolution in a common island environment. However, spectral
analysis of phylogenetic splits showed that although monophyly of island
haplotypes is favored, there is also substantial support for their polyphyletic
origin. We attribute the latter to the confounding effect of homoplasy at
multistate sites and to the relatively rapid sequence of colonization events
which provided insufficient time for the accumulation of strong phylogenetic
signal. These problems are likely to be significant impediments in attempts to
test hypotheses of phylogenetic histories of recently evolved populations and
taxa.
PMID- 10191066
TI - Cytochrome b phylogeny of North American hares and jackrabbits (Lepus,
lagomorpha) and the effects of saturation in outgroup taxa.
AB - Jackrabbits and hares, members of the genus Lepus, comprise over half of the
species within the family Leporidae (Lagomorpha). Despite their ecological
importance, potential economic impact, and worldwide distribution, the evolution
of hares and jackrabbits has been poorly studied. We provide an initial
phylogenetic framework for jackrabbits and hares so that explicit hypotheses
about their evolution can be developed and tested. To this end, we have collected
DNA sequence data from a 702-bp region of the mitochondrial cytochrome b gene and
reconstructed the evolutionary history (via parsimony, neighbor joining, and
maximum likelihood) of 11 species of Lepus, focusing on North American taxa. Due
to problems of saturation, induced by multiple substitutions, at synonymous
coding positions between the ingroup taxa and the outgroups (Oryctolagus and
Sylvilagus), both rooted and unrooted trees were examined. Variation in tree
topologies generated by different reconstruction methods was observed in analyses
including the outgroups, but not in the analyses of unrooted ingroup networks.
Apparently, substitutional saturation hindered the analyses when outgroups were
considered. The trees based on the cytochrome b data indicate that the taxonomic
status of some species needs to be reassessed and that species of Lepus within
North America do not form a monophyletic entity.
PMID- 10191067
TI - Molecular phylogeny and evolution of Sorex shrews (Soricidae: insectivora)
inferred from mitochondrial DNA sequence data.
AB - Shrews of the genus Sorex are characterized by a Holarctic distribution, and
relationships among extant taxa have never been fully resolved. Phylogenies have
been proposed based on morphological, karyological, and biochemical comparisons,
but these analyses often produced controversial and contradictory results.
Phylogenetic analyses of partial mitochondrial cytochrome b gene sequences (1011
bp) were used to examine the relationships among 27 Sorex species. The molecular
data suggest that Sorex comprises two major monophyletic lineages, one restricted
mostly to the New World and one with a primarily Palearctic distribution.
Furthermore, several sister-species relationships are revealed by the analysis.
Based on the split between the Soricinae and Crocidurinae subfamilies, we used a
95% confidence interval for both the calibration of a molecular clock and the
subsequent calculation of major diversification events within the genus Sorex.
Our analysis does not support an unambiguous acceleration of the molecular clock
in shrews, the estimated rate being similar to other estimates of mammalian
mitochondrial clocks. In addition, the data presented here indicate that
estimates from the fossil record greatly underestimate divergence dates among
Sorex taxa.
PMID- 10191068
TI - A phylogeny of aphid parasitoids (Hymenoptera: Braconidae: Aphidiinae) inferred
from mitochondrial NADH 1 dehydrogenase gene sequence.
AB - Wasps of the braconid subfamily Aphidiinae are solitary endoparasitoids of
aphids. Several aspects of their biology have been the focus of intuitive
evolutionary hypotheses which could be tested with a robust phylogeny.
Phylogenetic hypotheses have been proposed previously for aphidiines based on
morphology, embryology, and DNA sequences. However, many of them are based on a
limited number of characters and/or taxa and lack congruence. In addition, many
of the inferred phylogenies have not been based upon cladistic analysis.
Therefore, a phylogenetic study of Aphidiinae was undertaken, utilizing 465 bp of
DNA sequence of the mitochondrial NADH1 dehydrogenase gene. DNA sequences were
obtained from 40 taxa, including 14 genera and three outgroups. It is suggested
that in agreement with most of the previously proposed phylogenies, the
aphidiines, each of the three recognized tribes (Praini, Ephedrini, Aphidiini),
and most genera are monophyletic. In contrast to previously proposed phylogenies,
the clade of Praon + Dyscritulus (=Praini), rather than Ephedrini, is basal among
the aphidiines.
PMID- 10191069
TI - Molecular phylogeny of Palearctic-African Acrocephalus and Hippolais Warblers
(Aves: Sylviidae).
AB - Phylogenetic relationships of the reed warbler group (genera Acrocephalus,
Hippolais, Chloropeta; Aves: Passeriformes) and their potential relatives were
studied using nucleotide sequences (1 kb) of the mitochondrial cytochrome b gene.
This species-rich but morphologically poorly differentiated group of
insectivorous passerines is distributed in Eurasia, Africa, and Australasia.
Intergeneric relationships were poorly resolved, but monophyly of the reed
warbler group (including Chloropeta) versus other Sylviidae was strongly
supported. A basal polytomy within the reed warbler group consists of seven
branches and may indicate a rapid early radiation. In the genus Acrocephalus
three major clades were identified, which corresponded to phenotypic groups
characterized by body size and plumage patterns. However, current delimitation of
some subgenera (Acrocephalus, Lusciniola, Bebrornis) is at variance with our
phylogeny estimate, and appropriate revisions are proposed. The genus Hippolais,
which may or may not be monophyletic, consisted of two well-supported clades of
four species each. Some Acrocephalus taxa whose species status had been doubted
(griseldis, tangorum, orientalis, australis) proved to be highly distinct
genetically. Genetic distances between members of two pairs of allopatric
Hippolais taxa (caligata/rama; opaca/elaeica) were as large or larger than
between other closely related warbler species. Overall, cytochrome b sequences
resolved phylogenetically young relationships quite well, whereas more ancient
nodes remained poorly resolved.
PMID- 10191070
TI - Phylogenetic relationships of the enigmatic angiosperm family Podostemaceae
inferred from 18S rDNA and rbcL sequence data.
AB - The phylogenetic relationships of some angiosperm families have remained
enigmatic despite broad phylogenetic analyses of rbcL sequences. One example is
the aquatic family Podostemaceae, the relationships of which have long been
controversial because of major morphological modifications associated with their
aquatic habit. Podostemaceae have variously been associated with Piperaceae,
Nepenthaceae, Polygonaceae, Caryophyllaceae, Scrophulariaceae, Rosaceae,
Crassulaceae, and Saxifragaceae. Two recent analyses of rbcL sequences suggest a
possible sister-group relationship of Podostemaceae to Crassulaceae
(Saxifragales). However, the branch leading to Podostemaceae was long, and use of
different outgroups resulted in alternative placements. We explored the
phylogenetic relationships of Podostemaceae using 18S rDNA sequences and a
combined rbcL + 18S rDNA matrix representing over 250 angiosperms. In analyses
based on 18S rDNA data, Podostemaceae are not characterized by a long branch; the
family consistently appears as part of a Malpighiales clade that also includes
Malpighiaceae, Turneraceae, Passifloraceae, Salicaceae, Euphorbiaceae, Violaceae,
Linaceae, Chrysobalanaceae, Trigoniaceae, Humiriaceae, and Ochnaceae.
Phylogenetic analyses based on a combined 18S rDNA + rbcL data set (223 ingroup
taxa) with basal angiosperms as the outgroup also suggest that Podostemaceae are
part of a Malpighiales clade. These searches swapped to completion, and the
shortest trees showed enhanced resolution and increased internal support compared
to those based on 18S rDNA or rbcL alone. However, when Gnetales are used as the
outgroup, Podostemaceae appear with members of the nitrogen fixing clade (e.g.,
Elaeagnaceae, Ulmaceae, Rhamnaceae, Cannabaceae, Moraceae, and Urticaceae). None
of the relationships suggested here for Podostemaceae receives strong bootstrap
support. Our analyses indicate that Podostemaceae are not closely allied with
Crassulaceae or with other members of the Saxifragales clade; their closest
relatives, although still uncertain, appear to lie elsewhere in the rosids.
PMID- 10191071
TI - Evolution of the ribosomal RNA internal transcribed spacer one (ITS-1) in cichlid
fishes of the Lake Victoria region.
AB - The nucleotide sequences of the first internal transcribed spacer (ITS-1) of the
ribosomal RNA gene cluster have been determined for 11 species of closely related
endemic cichlid fishes of the Lake Victoria region (LVR) and 6 related East
African cichlids. The ITS-1 sequences confirmed independently derived basal
phylogenies, but provide limited insight within this species flock. The line
leading to Pseudocrenilabrus multicolor arose early, close to the divergence
event that separated the tilapiine and haplochromine tribes of the "African
Group" of the family Cichlidae. In this phylogeny, Astatoreochromis alluaudi and
the riverine Astatotilapia burtoni are sister taxa, which together are a sister
group to a monophyletic assemblage including both Lake Victoria and Lake Edward
taxa. The ITS-1 data support the monophyly of haplochromine genera across lakes.
Since Lake Victoria is believed to have been dry between 14, 500 and 12,400 BPE,
the modern assemblage must have been derived from reinvasion by the products of
earlier cladogenesis events. Thus, although the regional superflock is
monophyletic, the haplochromines of Lake Victoria itself did not evolve in situ
from a single ancestor.
PMID- 10191072
TI - Relationships among the cyclostome braconid (Hymenoptera: Braconidae) subfamilies
inferred from a mitochondrial tRNA gene rearrangement.
AB - The arrangement of mitochondrial tRNA genes for lysine (K) and aspartate (D) from
the junction of the cytochrome oxidase II and ATPase 8 genes was determined in a
range of hymenopteran taxa. This indicated that the ancestral arrangement for the
order is 'KD', as found in the Diptera (represented by Drosophila and Anopheles)
and basal Orthoptera. Most Hymenoptera that evolved after the appearance of
parasitism also have the 'KD' arrangement, including noncyclostome braconids.
However, most cyclostome braconids have either a 'DK' or a 'DHK' arrangement
(where 'H' refers to the tRNA gene for Histidine). In both cases, the aspartate
tRNA gene is encoded on the mitochondrial N-strand, rather than the J-strand as
is usually the case. This rearrangement identified a monophyletic group not
previously recognized, consisting of Rogadinae + Braconinae + Gnamptodontinae +
Histeromerinae + Rhyssalinae + Betylobraconinae + Opiinae + Alysiinae. Only one
cyclostome subfamily (Doryctinae) retained the 'KD' arrangement, suggesting this
to be the most basal of the cyclostome subfamilies, consistent with
ectoparasitism being plesiomorphic for the cyclostomes. However, the Aphidiinae
also retained the 'KD' arrangement, leaving unresolved the issue of whether they
should be included within the cyclostomes.
PMID- 10191073
TI - Phylogeny of the hard ticks (Ixodidae) inferred from 18S rRNA indicates that the
genus Aponomma is paraphyletic.
AB - We examined the phylogeny of ticks (Acari:Parasitiformes:Ixodida) and their
closest known mite relatives (Acari:Parasitiformes:Mesostigmata and Holothyrida)
using 18S rRNA sequences. In our analyses, we included sequences from 36 taxa.
Sequences for 13 hard ticks (Family Ixodidae), 5 soft ticks (Family Argasidae),
and 2 mesostigmatid mites were obtained from the GenBank database and we
generated sequences for 15 hard ticks and 1 holothyrid mite. Ten of these tick
species were endemic to Australia. Our analyses indicated that the suborder
Holothyrida is more closely related to Ixodida than to Mesostigmata, the group
used as outgroup in earlier molecular studies. This finding is consistent with
Lehtinen's (1991) hypothesis that the Holothyrida rather than the Mesostigmata is
the sister-group to the Ixodida. Within the hard ticks the genus Aponomma and
thus the family Amblyomminae were paraphyletic. Taxonomic revision of these taxa
is needed. The genus Amblyomma was paraphyletic without the inclusion of
"typical" Aponomma species (Ap. latum and Ap. fimbriatum). There was a basal
divergence between endemic Australian and other species in both the Metastriata
and the Prostriata divisions of the hard ticks.
PMID- 10191074
TI - Phylogeny of the arachnid order Opiliones (Arthropoda) inferred from a combined
approach of complete 18S and partial 28S ribosomal DNA sequences and morphology.
AB - The phylogenetic relationships among the main evolutionary lines of the arachnid
order Opiliones were investigated by means of molecular (complete 18S rDNA and
the D3 region of the 28S rDNA genes) and morphological data sets. Equally and
differentially weighted parsimony analyses of independent and combined data sets
provide evidence for the monophyly of the Opiliones. In all the analyses, the
internal relationships of the group coincide in the monophyly of the following
main groups: Cyphophthalmi, Eupnoi Palpatores, Dyspnoi Palpatores, and
Laniatores. The Cyphophthalmi are monophyletic and sister to a clade that
includes all the remaining opilionid taxa (=Phalangida). Within the Phalangida
the most supported hypothesis suggests that Palpatores are paraphyletic, as
follows: (Eupnoi (Dyspnoi + Laniatores)), but the alternative hypothesis
(Laniatores (Eupnoi + Dyspnoi)) is more parsimonious in some molecular data
analyses. Relationships within the four main clades are also addressed. Evolution
of some morphological characters is discussed, and plesiomorphic states of these
characters are evaluated using molecular data outgroup polarization. Finally,
Martens' hypothesis of opilionid evolution is assessed in relation to our
results.
PMID- 10191075
TI - Phylogenetic analysis of vertebrate and invertebrate Delta/Serrate/LAG-2 (DSL)
proteins.
AB - Delta/Serrate/LAG-2 (DSL) proteins are putative transmembrane signaling molecules
that regulate cell differentiation in metazoans. DSL proteins are characterized
by the presence of a motif unique to these proteins, the DSL motif, and a
variable number of tandemly repeated copies of an epidermal growth factor-like
(EGF) motif. We have completed a phylogenetic analysis of 15 DSL proteins from
eight species. Our findings reveal that at least one gene duplication occurred
prior to the divergence of the Drosophila melanogaster and vertebrate lineages,
with subsequent duplications in vertebrates. The three known Caenorhabditis
elegans proteins likely arose by two independent duplications in the nematode
lineage. Analysis of EGF repeats suggests that EGF 2 has been conserved among DSL
proteins in vertebrates and D. melanogaster. The sequences of two EGF repeats
have been perfectly conserved in vertebrate orthologs: EGF 2 in Delta and EGF 15
in Jagged/Serrate. Finally, the linear order of EGF repeats has been conserved in
the vertebrate Jagged/Serrate orthologs and vertebrate Delta orthologs.
PMID- 10191076
TI - A comparison of cytochrome b and DNA hybridization data bearing on the phylogeny
of swallows (Aves: Hirundinidae).
AB - Cytochrome b sequence data from 17 species representing 16 genera of swallows
(Aves: Hirundinidae) were compared with DNA-DNA hybridization data from the same
species in a taxonomic congruence assessment of swallow phylogeny. In the
process, subsets (partitions) of the cytochrome b sequence data were examined in
light of the DNA hybridization distances to assess their potential phylogenetic
informativeness. When the sequence data were weighted-with or without reference
to the DNA hybridization data-they produced parsimony and maximum likelihood (but
not distance) trees that were largely congruent with the DNA hybridization tree.
To this extent, the cytochrome b data supported many of the phylogenetic
conclusions based on the DNA hybridization tree and vice versa. However, the
cytochrome b data produced largely unresolved trees when branch robustness was
tested by bootstrapping and other methods. This poor resolution appeared to be
caused by a lack of hierarchical structure in the cytochrome b distances, which
were confined to a narrow range (between 10-13%), compressed by saturation, and
noisy. Partition analysis by codon sites and protein domains yielded typical
avian cytochrome b patterns, except for idiosyncrasies attributable to the
genetic divergence level of swallows in comparison to other groups of birds whose
cytochrome b sequences have been analyzed.
PMID- 10191077
TI - A nested analysis of song groups and species boundaries in the Hawaiian cricket
genus Laupala.
PMID- 10191078
TI - Development of a feline whole genome radiation hybrid panel and comparative
mapping of human chromosome 12 and 22 loci.
AB - A 5000-rad whole genome radiation hybrid panel is described for the domestic cat,
derived from irradiated male feline fibroblasts fused to a recipient hamster cell
line. A panel of 93 cell lines has an estimated retention frequency of 0.39
(range 0.13-0.71) based upon PCR typing of 54 feline markers. To test the panel's
utility, we determined the order of 16 Type I (coding gene) loci, 14 Type II
(microsatellite) loci, and 1 endogenous retroviral element on feline chromosomes
B4 and D3. Assessment of marker order derived from the RH panel was compared to
assignments of the same loci using interspecies backcross mapping data, human
homologue positions, and human-cat chromosome painting homologies. Assessment of
concordant and discordant marker order for these loci provides improved
resolution into the evolution of subchromosomal genome organizations and the
methods to track them in these species.
PMID- 10191079
TI - A genetic linkage map of microsatellites in the domestic cat (Felis catus).
AB - Of the nonprimate mammalian species with developing comparative gene maps, the
feline gene map (Felis catus, Order Carnivora, 2N = 38) displays the highest
level of syntenic conservation with humans, with as few as 10 translocation
exchanges discriminating the human and feline genome organization. To extend this
model, a genetic linkage map of microsatellite loci in the feline genome has been
constructed including 246 autosomal and 7 X-linked loci. Two hundred thirty-five
dinucleotide (dC. dA)n. (dG. dT)n and 18 tetranucleotide repeat loci were
identified and genotyped in a two-family, 108-member multigeneration interspecies
backcross pedigree between the domestic cat (F. catus) and the Asian leopard cat
(Prionailurus bengalensis). Two hundred twenty-nine loci were linked to at least
one other marker with a lod score >/=3.0, identifying 34 linkage groups.
Representative markers from each linkage group were assigned to specific cat
chromosomes by somatic cell hybrid analysis, resulting in chromosomal assignments
to 16 of the 19 feline chromosomes. Genome coverage spans approximately 2900 cM,
and we estimate a genetic length for the sex-averaged map as 3300 cM. The map has
an average intragroup intermarker spacing of 11 cM and provides a valuable
resource for mapping phenotypic variation in the species and relating it to gene
maps of other mammals, including human.
PMID- 10191081
TI - An integrated physical and gene map of human distal chromosome 17q24-proximal
17q25 encompassing multiple disease loci.
AB - Genetic mapping studies suggest that a small interval on human chromosome distal
17q24-proximal 17q25 harbors genes involved in sporadic breast and ovarian
tumorigenesis and in the autosomal dominant disorders hereditary neuralgic
amyotrophy and tylosis with esophageal cancer. Prior to this study, isolated
genomic clones and markers were assigned to this interval but integrated physical
maps were not available. We improved resolution by isolating 52 additional clones
and developing 24 additional markers. Genomic clones spanning distal 17q24
proximal 17q25 were organized into a contig with two gaps that encompassed 14
existing genetic markers, 8 known genes (GALR2, AANAT, ENVL, SFRS2, SEC14L,
DNAH17, API4, and TK1), and 11 previously identified expressed sequence tags.
This integrated map provides a foundation for identifying additional candidate
genes for the disorders mapped to this interval.
PMID- 10191080
TI - A radiation hybrid breakpoint map of the acute myeloid leukemia (AML) and limb
girdle muscular dystrophy 1A (LGMD1A) regions of chromosome 5q31 localizing 122
expressed sequences.
AB - We have constructed a high-resolution map of a 6-Mb interval of human chromosome
5, band q31, incorporating 175 sequence tagged sites, of which 33 are genetic
polymorphisms and 122 are nonredundant expressed sequences. The map was assembled
initially as a YAC contig, incorporating data from radiation hybrid maps. To
improve resolution and to identify errors in the databases, a radiation hybrid
breakpoint map was developed for the interval, which included hybrids from both
Stanford G3 and GeneBridge 4 panels. This novel approach facilitated the
integration of one RH panel with another and enabled the identification and
localization of new, previously unmapped ESTs from the radiation hybrid
databases. ESTs were assembled into overlapping transcription units and ordered
with respect to polymorphic markers in the region, resulting in a comprehensive
map that incorporates markers from multiple different types of maps. This map of
5q31 will facilitate gene discovery efforts for several disorders, including limb
girdle muscular dystrophy type 1A and the genes deleted in acute myeloid
leukemias and myelodysplasia. The study demonstrates the utility of a radiation
hybrid breakpoint panel for correction of map errors and for the efficient
identification of new transcript units in a large genomic interval.
PMID- 10191082
TI - The Drosophila melanogaster 60A chromosomal division is extremely dense with
functional genes: their sequences, genomic organization, and expression.
AB - We cloned and sequenced genomic DNA contigs spanning over 45 kb, surrounding the
insertion site of the P-element that is responsible for the developmental defects
in the ken and barbie (ken) mutant of Drosophila. This region harbors 10
functional transcription units, in addition to the already well-characterized
TGFbeta-60A gene. These include the genes, undefined 1 (UD1), UD2, and UD3, each
coding for proteins of unknown function, the ken gene encoding a new Kruppel-like
putative transcription factor, the fly homologues of the mammalian mitochondrial
trifunctional enzyme (thiolase), and the TAR DNA-binding protein-43 (TBPH), the
first nonvertebrate member of the transmembrane 4 superfamily (TM4SF) gene, a new
homeodomain gene, and a gene coding for a putative nuclear binding protein (PNBP)
that is homologous to maleless, and a Copia-like element. UD3 exists in an intron
of the maleless homologue, yet is expressed independent of it. The UD1 and TM4SF
genes orient in a tail-to-tail manner with their 3' untranslated region sequences
overlapping over 44 nucleotides. Thus the partial overlap and intraintronic
organization permitted dense packing of the functional genes within a short
segment of the genome.
PMID- 10191083
TI - Retinal dystrophy of Swedish briard/briard-beagle dogs is due to a 4-bp deletion
in RPE65.
AB - The RPE65 gene encodes a 65-kDa microsomal protein expressed exclusively in
retinal pigment epithelium (RPE). Mutations in the human RPE65 gene have recently
been identified in patients with autosomal recessive, severe, childhood-onset
retinal dystrophy. Here we report the characterization of a 2.4-kb canine Rpe65
cDNA. The longest open reading frame predicts a 533-amino-acid protein with a
calculated molecular mass of about 61 kDa prior to protein modification. Sequence
comparison shows that RPE65 is highly conserved throughout mammalian evolution.
We have identified a homozygous 4-bp deletion (485delAAGA) in putative exon 5 of
the canine Rpe65 gene in affected animals of a highly inbred kinship of Swedish
briard/briard-beagle dogs, in which an autosomal recessive, early-onset, and
progressive retinal dystrophy segregates. The deletion results in a frameshift
and leads to a premature stop codon after inclusion of 52 canine RPE65-unrelated
amino acids from residue 153 onward. More than two-thirds of the wildtype
polypeptide chain will be missing, and the mutant protein is most likely
nonfunctional (null allele). Clinical features of the canine disease are quite
similar to those described in human. Therefore this form of canine retinal
dystrophy provides an attractive animal model of the corresponding human disorder
with immediate significance for various therapeutic approaches, including RPE
transplantation.
PMID- 10191084
TI - A 1-Mb bacterial clone contig spanning the endometrial cancer deletion region at
1p32-p33.
AB - Our laboratory previously reported a high frequency of loss of heterozygosity
(LOH) at 1p32-p33 in endometrial cancers. LOH at 1p32-p33 is a specific feature
of one of the most aggressive forms of endometrial carcinoma, uterine papillary
serous cancer (UPSC). The minimum region of allelic loss in UPSC is defined by
D1S190 and D1S447, an interval corresponding to less than 1 cM. Here we describe
the construction and characterization of a sequence-ready clone contig that spans
the deletion region. The contig consists of 24 bacterial artificial chromosome
clones and 18 P1 artificial chromosome clones and spans approximately 1050 kb.
The consensus region of allelic loss between D1S190 and D1S447 represents
approximately 792 kb. Eight previously described ESTs have been positioned within
the contig.
PMID- 10191085
TI - Closing in on the BPES gene on 3q23: mapping of a de Novo reciprocal
translocation t(3;4)(q23;p15.2) breakpoint within a 45-kb cosmid and mapping of
three candidate genes, RBP1, RBP2, and beta'-COP, distal to the breakpoint.
AB - BPES is a genetic disorder presenting with blepharophimosis, ptosis of the
eyelids, epicanthus inversus, and telecanthus. BPES type I is associated with
female infertility, whereas type II presents without additional symptoms.
Hitherto, it remains unknown whether BPES type I results from a defect in a
single gene or from a contiguous gene syndrome. Previous cytogenetic and linkage
analyses have assigned a BPES locus to 3q23, in a 5-cM interval between D3S1615
and D3S1316. In this report, we describe the molecular and physical
characterization of the 3q23 breakpoint in a BPES patient with a
t(3;4)(q23;p15.2) translocation. Eight YACs located around and within the D3S1615
D3S1316 interval were mapped relative to the 3q23 breakpoint; 5 YACs spanning the
3q23 breakpoint were identified. Thirteen STSs and ESTs were localized on the YAC
map. Subsequent hybridization of 2 YACs spanning the breakpoint to the Human
RPCI1 PAC Library and the Human Chromosome 3 LLNL Cosmid Library resulted in the
identification of 12 PACs and 50 cosmids respectively, allowing the construction
of a detailed PAC and cosmid physical map. A refined position-telomeric to the
breakpoint-of 3 candidate genes, cellular retinol-binding proteins 1 and 2 (RBP1,
RBP2) and the coatomer beta' subunit (beta'-COP), was obtained on this physical
map. Furthermore, a PAC and cosmid contig encompassing the breakpoint was
constructed. PAC 169-C 10 and cosmid 11-L 10 crossing the breakpoint have sizes
of 110 and 45 kb, respectively. The isolation of coding sequences in these clones
and in the rest of the contig will greatly facilitate further efforts toward
positional cloning of the gene(s) involved in BPES.
PMID- 10191086
TI - cDNA and genomic cloning of mouse aquaporin-2: functional analysis of an
orthologous mutant causing nephrogenic diabetes insipidus.
AB - As the first step in generating a transgenic mouse model of nephrogenic diabetes
insipidus (NDI), we have analyzed the mouse aquaporin-2 (Aqp2) cDNA and gene and
generated a mutated Aqp2 orthologous to NDI-causing human AQP2-T126M. Aqp2 cDNA
was isolated from mouse kidney and encoded a 271-amino-acid protein with 90.4%
identity to human AQP2. Expression in Xenopus oocytes indicated that Aqp2 encoded
a mercurial-sensitive, water-selective channel. Northern blot analysis showed a
single 1.7-kb Aqp2 transcript expressed only in kidney (medulla > cortex);
transcript expression was increased approximately 20-fold in 48-h water-deprived
mice. Immunoblot analysis revealed a 29-kDa glycoprotein in mouse kidney.
Sequence comparison of the Aqp2 cDNA with a 5.5-kb mouse genomic DNA indicated
three introns (lengths 2.4, 0.9, and 0.6 kb) separating four exons with
boundaries at amino acids 120, 175, and 202. Genomic Southern blot analysis
revealed a single-copy Aqp2 gene. The mutant Aqp2-T126M was water permeable when
expressed in Xenopus oocytes, but was retained at the endoplasmic reticulum (ER)
in transfected mammalian cells. The chemical chaperone glycerol produced a
redistribution of Aqp2-T126M from ER to plasma membrane/endosomes. These results
establish a basis for an Aqp2-T126M transgenic knock-in model of NDI.
PMID- 10191087
TI - Genomic organization of the human galpha14 and Galphaq genes and mutation
analysis in chorea-acanthocytosis (CHAC).
AB - Chorea-acanthocytosis (CHAC) (OMIM 200150) is a rare neurological syndrome
characterized by neurodegeneration in combination with morphologically abnormal
red cells (acanthocytosis). A partial yeast artificial chromosome contig of the
CHAC critical region on chromosome 9q21 has been constructed, and 21 expressed
sequence tags have been mapped. We have subsequently cloned Galpha14, a member of
the G-protein alpha-subunit multigene family, and have identified Galphaq in the
contig. The genomic structure of both genes has been established after
construction of a bacterial artificial chromosome contig that showed Galphaq and
Galpha14 to be in a head-to-tail arrangement (Cen-Galphaq-Galpha14-qter).
Northern analysis found Galphaq to be ubiquitously expressed and Galpha14 to
display a more restricted pattern of expression. Mutation analysis of the coding
regions and splice sites for Galphaq and Galpha14 in 10 affected individuals from
different families identified no changes likely to cause disease; however, two
distinct single nucleotide polymorphisms in the coding region of Galpha14 have
been identified. This study has excluded two plausible candidate genes from
involvement in CHAC and has provided a solid platform for a positional cloning
initiative.
PMID- 10191088
TI - Sperizin is a murine RING zinc-finger protein specifically expressed in Haploid
germ cells.
AB - Through the preparation of a subtracted cDNA library, we have extensively
isolated genes whose expression is induced in mouse spermatogenic cells. One of
the genes encoded a protein with a RING zinc-finger motif, which we termed
sperizin (spermatid-specific ring zinc finger). Transcription of the sperizin
gene was not observed in prepubertal testis, but became detectable at day 23.
Northern and in situ hybridization analyses indicated that the sperizin gene was
exclusively expressed in the round spermatid. The sperizin gene is intronless,
and GFP-tagged sperizin was found to be localized in the cytoplasm of ectopically
expressed somatic cultured cells. We assigned the chromosomal localization of the
sperizin gene to chromosome 17 using an interspecific backcross mapping panel.
The data suggest that we have identified a new member of the RING-finger family
of proteins that may be involved in spermatogenesis.
PMID- 10191089
TI - Close physical linkage of human troponin genes: organization, sequence, and
expression of the locus encoding cardiac troponin I and slow skeletal troponin T.
AB - Based on chromosomal mapping data, we recently revealed an unexpected linkage of
troponin genes in the human genome: the six genes encoding striated muscle
troponin I and troponin T isoforms are located at three chromosomal sites, each
of which carries a troponin I-troponin T gene pair. Here we have investigated the
organization of these genes at the DNA level in isolated P1 and PAC genomic
clones and demonstrate close physical linkage in two cases through the isolation
of individual clones containing a complete troponin I-troponin T gene pair. As an
initial step toward fully characterizing this pattern of linkage, we have
determined the organization and complete sequence of the locus encoding cardiac
troponin I and slow skeletal troponin T and thereby also provide the first
determination of the structure and sequence of a slow skeletal troponin T gene.
Our data show that the genes are organized head to tail and are separated by only
2.6 kb of intervening sequence. In contrast to other troponin genes, and despite
their close proximity, the cardiac troponin I and slow skeletal troponin T genes
show independent tissue-specific expression. Such close physical linkage has
implications for the evolution of the troponin gene families, for their
regulation, and for the analysis of mutations implicated in cardiomyopathy.
PMID- 10191090
TI - Functional characterization of the human PAX3 gene regulatory region.
AB - Spatiotemporal expression of the PAX3 gene is tightly regulated during
development. We have isolated and sequenced the 5'-flanking regulatory region of
human PAX3. Primer extension and ribonuclease protection mapping revealed that
transcription is initiated from a single start site downstream of a TATA-like
motif in human brain and peripheral tissues. Functional dissection of the gene's
5'-flanking region, which had been fused to a luciferase reporter gene and
transiently expressed in rhabdomyosarcoma (RD) and cos-7 cells, indicated that
the upstream region of PAX3 contains multiple positive and negative cis-acting
regulatory elements. While the basal promoter is likely to be driven by two CCAAT
boxes located at nucleotide positions -90 and -135, a cluster of regulatory
elements acting as a strong repressor was detected between nucleotides -1200 and
650. Comparison of human and murine sequences revealed more than 90% identity in
this segment. A polymorphic (CA)n repeat sequence and a G/C substitution are
located 337 bp and 328 bp upstream of the transcription start site, respectively.
PCR-based systematic screening for length variations in 225 unrelated individuals
of a Caucasian population showed a bimodal distribution of multiple alleles
containing between 13 and 30 repeat units. Although the (CA)25 variant of this
PAX3 gene-linked polymorphic region (PAX3LPR) conferred lower transcriptional
efficiency on the PAX3 promoter, a regulatory impact of the PAX3LPR on PAX3
expression related to brain plasticity and function remains to be demonstrated.
PMID- 10191091
TI - The human serum deprivation response gene (SDPR) maps to 2q32-q33 and codes for a
phosphatidylserine-binding protein.
AB - The serum deprivation response gene (SDPR, alias sdr) has been previously
isolated for its high mRNA expression in serum-starved cells compared to contact
inhibited NIH3T3 cells; such regulation is not observed in single-oncogene
transformed NIH3T3 cells after serum starvation. More recently Sdpr has been
identified as a substrate of protein kinase C (PKC): this interaction determines
the compartimentalization of PKC to caveolae, a plasma membrane invagination of
which Sdpr is a major component. Lack of Sdpr-PKC interaction in transformed
cells has been proposed to be involved in the alteration of PKC subcellular
localization and substrate specificity. Here we report the cloning of the human
SDPR homologue (HGMW-approved symbol SDPR) and its mapping to 2q32-q33 in the
human genome. In analogy with the murine system, SDPR mRNA expression is
increased when human fibroblasts are serum starved, it becomes down-regulated
during synchronous cell-cycle reentry, but it is not induced in cells arrested by
contact inhibition. Analysis of SDPR expression in human tissues reveals a near
ubiquitous expression, with highest levels found in heart and lung. We show that
human SDPR encodes PS-p68, a previously characterized phosphatidylserine-binding
protein purified from human platelets. Accordingly, recombinant Sdpr is able to
specifically bind phosphatidylserine in the absence of Ca2+. SDPR is homologous
to two genes in the databank, one of which, srbc, is similarly regulated during
growth arrest and encodes a phosphatidylserine-binding protein that is a
substrate of PKC.
PMID- 10191092
TI - A novel testis-specific metallothionein-like protein, tesmin, is an early marker
of male germ cell differentiation.
AB - We have cloned a novel cDNA encoding testis-specific metallothionein-like
protein, tesmin, by randomized RT-PCR on RNA from mouse tissues. Two tesmin
related transcripts (2.2 and 1.8 kb) in mouse and one (2.1 kb) in human were
detected and cloned. These encode a cysteine-rich 32-kDa protein that contained a
metallothionein-like motif. In situ hybridization analysis in adult mouse testis
showed that tesmin is specifically expressed in spermatocytes. Quantitative RT
PCR at different stages of mouse postnatal development (days 4, 8, 12, 18, and
42) revealed that tesmin is expressed as early as day 8 and coincides with the
entry of germ cells into meiosis. Furthermore, adult W/Wv sterile mice that
harbor the c-kit mutation lacked tesmin expression. The gene is assigned to mouse
chromosome 19B, which has been reported to translocate (11;19) in male sterile
mice.
PMID- 10191093
TI - Cloning and characterization of NEU2, a human gene homologous to rodent soluble
sialidases.
AB - Sialidases (EC 3.2.1.18) are a group of glycohydrolytic enzymes, widely
distributed in nature, that cleave sialic acid residues from the oligosaccharide
components of glycoconjugates. All of the sialidase enzymes thus far
characterized share an Asp block, repeated three to five times in the primary
structure, and an F/YRIP sequence motif that is part of the active site. Using a
sequence homology-based approach, we have identified a novel human gene, named
NEU2, mapping to chromosome 2q37. The nucleotide sequence analysis of the gene
has shown that it contains only one intron of about 1.25 kb, and the longest open
reading frame encodes a protein of 380 amino acids, with a two-Asp block
consensus, and the YRIP sequence. In the putative promoter sequence there are a
classical TATAA box and four E boxes, which are consensus binding sites for
muscle-specific transcription factors. Northern blot analysis revealed expression
of the NEU2 transcript only in skeletal muscle.
PMID- 10191095
TI - Characterization of the mouse A3 adenosine receptor gene: exon/intron
organization and promoter activity.
AB - In a previous study, we reported the expression of A3 adenosine receptor mRNA in
rat vascular smooth muscle cells (VSMC) and demonstrated that its levels affect
the intracellular concentration of cAMP. In the current study, we isolated the
mouse A3 adenosine receptor (A3AR) gene, characterized its structure, and defined
its promoter activity in VSMC. The mouse A3AR gene fragment available to us has 3
kb of coding sequences, composed of two exons separated by a single intron, and
2.3 kb of 5' noncoding region. The promoter region lacks "TATA" and "CAAT" boxes,
but contains an initiator consensus sequence. In accordance with Northern blot
analysis of A3AR mRNA, transient transfection experiments showed that the
promoter activity of this fragment was significant in VSMC and astrocytes and
high in mast cells. The characterization of the mouse A3 adenosine receptor gene
and insight into its promoter region will allow further studies to determine the
physiological importance of its transcriptional regulation in different tissues.
PMID- 10191094
TI - Localization of a human nucleoporin 155 gene (NUP155) to the 5p13 region and
cloning of its cDNA.
AB - Nucleoporins are the main components of nuclear pore complexes (NPCs) involved in
nucleo-cytoplasmic transport. Starting with an expressed DNA fragment retrieved
by exon trapping from pooled human BAC clones mapped to the short arm of
chromosome 5, we identified a human nucleoporin cDNA sequence by PCR from a human
testis cDNA library. The coding sequence showed high homology to that of the rat
nucleoporin 155 (Nup155) cDNA. FISH analysis with the human BAC clone as probe
localized the human NUP155 gene to chromosome band 5p13. Northern analysis showed
that the human NUP155 gene was expressed at different levels in all tissues
tested. Two species of transcripts were observed with estimated lengths of 5.4
and 4.7 kb, respectively, in concordance with the finding of two alternative
polyadenylation sites in the cDNA. The genomic location of the human NUP155 gene
suggests a possible role in the mental and developmental retardation associated
with hemizygous deletions of the 5p13 region.
PMID- 10191096
TI - Identification of a zeta-crystallin (quinone reductase)-like 1 gene (CRYZL1)
mapped to human chromosome 21q22.1.
AB - To identify a new gene(s) located on the yeast artificial chromosome (YAC) clone
D142H8 that was mapped to human chromosome 21q22.1, purified YAC DNA from the
clone was utilized directly as a probe to screen a human brain cDNA library after
the suppression of human repetitive DNA. One cDNA clone hybridizing specifically
to the YAC D142H8 DNA was identified. The clone has an insert of 1341 bp and the
longest open reading frame of 349 amino acids. A search of GenBank revealed that
the clone has a high degree of homology to zeta-crystallin (quinone reductase) at
the amino acid level, and its nucleotide sequence represents the expressed
sequence from the 50-kb segment of the human chromosome 21q11.1. Thus a new gene
was named CRYZL1 (zeta-crystalline-like 1). Genomic Southern blot with total
human and yeast DNAs suggests that CRYZL1 might be a single-copy gene. The
fluorescence in situ hybridization procedure was applied, and the results showed
that the gene mapped to the human chromosome 21q22.1 subband. The CRYZL1 mRNA was
expressed in heart, brain, skeletal muscle, kidney, pancreas, liver, and lungs
but at different levels in different tissues.
PMID- 10191097
TI - Mapping of a cadherin gene cluster to a region of chromosome 5 subject to
frequent allelic loss in carcinoma.
AB - Cadherin adhesion molecules define cellular interactions during embryogenesis and
morphogenesis, while later in life they are responsible for maintaining tissue
integrity. Mutation and loss of expression of cadherins have been implicated in
the progression of some malignant tumors, suggesting that cadherins may also act
as tumor/metastasis suppressor genes. To determine the extent to which cadherin
loci could be affected by allelic losses, we used radiation hybrid mapping to
define the chromosomal position of five cadherin genes. A cadherin gene cluster
consisting of three genes was identified on the short arm of chromosome 5. This
region of the genome is subjected to frequent allelic loss in malignant disease.
PMID- 10191098
TI - Analysis of the spermine synthase gene region in Fugu rubripes, Tetraodon
fluviatilis, and Danio rerio.
AB - A prerequisite to understanding the evolution of the human X chromosome is the
analysis of synteny of X-linked genes in different species. We have focused on
the spermine synthase gene in human Xp22. 1. We show that whereas the human gene
spans a genomic region of 54 kb, the Fugu rubripes gene is encompassed in a 4.7
kb region. However, we could not find conserved synteny between this region of
human Xp22 and the equivalent F. rubripes region. A cosmid clone containing the
F. rubripes gene does not contain other X-linked genes. Instead we identified
homologs of human genes that are autosomally localized: the ryanodine receptor
type I (RYRI), which is implicated in malignant hyperthermia and central core
disease, and the HE6 gene. Comparison of the F. rubripes, Tetraodon fluviatilis,
mouse, human, and Danio rerio 5'UTRs of spermine synthase highlights conserved
sequences potentially involved in regulation. Interestingly, pseudogenes of this
gene that are present in the human and mouse genomes seem to be absent in the
compact F. rubripes genome. Analysis of a D. rerio PAC clone containing spermine
synthase shows an intermediate genomic size in this fish. Sequence analysis of
this PAC clone did not reveal other known genes: neither the RYRI gene, nor the
HE6 gene, nor other human Xp22 genes were identified.
PMID- 10191099
TI - Sequence analysis of genomic regions containing trinucleotide repeats isolated by
a novel cloning method.
AB - A method was developed for effective isolation of trinucleotide repeats from
genomic DNA. This method is based on the DNA polymerase reaction, which is
restricted with only two or three nucleotide substrates and primed by
biotinylated oligonucleotide probes. Sequences are then isolated by a
streptavidin biotin-trapping method. More than 80% of the clones from each
library contained more than eight trinucleotide repeats. Sequence analysis showed
that the characteristic dinucleotide flanking sequences usually confronting
various trinucleotide repeats are not found in the vicinity of CAG repeats,
suggesting that CAG repeats may have been generated through a mechanism different
from that of other trinucleotide repeats.
PMID- 10191100
TI - Chromosomal mapping of five mouse G protein gamma subunits.
AB - Heterotrimeric G proteins, composed of alpha, beta, and gamma subunits, transduce
signals from transmembrane receptors to a wide range of intracellular effectors.
The G protein gamma subunits, which play an indispensible role in this
communication, constitute a large and diverse multigene family. Using an
interspecific backcross panel, we have determined the mouse chromosomal locations
of five gamma subunit genes: gamma2, gamma8, gamma10, gamma12, and gammaCone.
Combined with previous mapping studies, these data indicate that, with the
possible exception of gamma1 and gamma11, the G protein gamma subunit genes are
well dispersed within the mouse and human genomes.
PMID- 10191101
TI - Interleukin-1 receptor cluster: gene organization of IL1R2, IL1R1, IL1RL2 (IL
1Rrp2), IL1RL1 (T1/ST2), and IL18R1 (IL-1Rrp) on human chromosome 2q.
AB - The family of interleukin-1 receptor-like genes currently has six known members.
We have constructed a contig of 10 overlapping human PAC clones that covers 530
kb and includes five of the six family members. The termini of the contig were
mapped to the interval between D2S373 and D2S176 (chromosome 2q12) by radiation
hybrid mapping. The contig contains the genes (cen --> tel), in the order given,
for the type II interleukin-1 (IL-1) receptor (IL1R2), the type I IL-1 receptor
(IL1R1), the IL-1 receptor-related protein 2 (IL1RL2), T1/ST2/fit-1 (IL1RL1), and
the IL-1 receptor-related protein 1, which has recently been shown to be a
component of the IL-18 receptor (IL18R1). We show that all the genes are
transcribed in the same direction, with IL1R2 being transcribed toward the
cluster. The only known family member that is absent from the human contig is the
IL-1 receptor accessory protein gene (IL1RAP), which maps to 3q28.
PMID- 10191102
TI - Subunit 3 of the COP9 signal transduction complex is conserved from plants to
humans and maps within the smith-magenis syndrome critical region in 17p11.2.
PMID- 10191103
TI - Mapping and mutational analysis of the human TAF2G gene encoding a p53 cofactor.
PMID- 10191104
TI - 12th International Mouse Genome Conference.
PMID- 10191105
TI - Seventh international congress on the neuronal ceroid-lipofuscinoses: NCL-98
PMID- 10191106
TI - Thirty years of Batten disease research: present status and future goals.
AB - From a meager beginning in 1968, when Batten disease or neuronal ceroid
lipofuscinosis was practically unheard of, tremendous advances have been made. It
is now recognized worldwide as the most common neurodegenerative disease in
children and young adults. It is recognized as a genetic disease. The infantile
form has been localized to chromosome 1 p32 and the juvenile form, to 16p12.1;
the gene for the late infantile is on chromosome 11p15 and for a variant form of
the late infantile, the gene lies on chromosome 15q21-23. Finally, the molecular
basis of the late infantile form is probably a pepstatin-insensitive lysomal
peptidase. The future is to identify carriers, prevent the disease, and develop
treatment by gene and enzyme replacement.
PMID- 10191107
TI - Genotype-phenotype correlations in neuronal ceroid lipofuscinosis due to
palmitoyl-protein thioesterase deficiency.
AB - The infantile form of neuronal ceroid lipofuscinosis (NCL) has been well studied
in Finland, where there is a high carrier frequency (1:70) for a single mutation
in the causative gene, CLN1, or PPT. We have recently studied a group of 29 NCL
subjects in the United States with palmitoyl-protein thioesterase (PPT)
deficiency and described 19 different CLN1/PPT mutations in our population. In
this report, we present a review of our previous findings, including a more
detailed analysis of phenotype-genotype correlations, and present previously
unpublished data concerning the clinical manifestations of the disorder in
children of families with multiple affected members. Our studies indicate that
about half of PPT-deficient patients in the United States are very similar to
Finnish infants with INCL, but that a different mutation (R151X) accounts for 40%
of U.S. alleles. The Finnish mutation (R122W) is rare in the United States. The
other half of U.S. PPT-deficient patients develop symptoms after the age of 2
years, much later than Finnish patients. One common mutation (the "Scottish"
allele, T75P) accounts for 13% of alleles and results in a juvenile-onset
phenotype that is clinically indistinguishable from JNCL with CLN3 mutations.
Other rare mutations were also associated with JNCL phenotypes, such as D79G and
G250V. A preliminary expression study of two of these mutant enzymes supports the
conclusion that juvenile-onset NCL (JNCL with GROD) is caused by missense
mutations in the PPT gene that result in mutated enzymes with residual PPT enzyme
activity.
PMID- 10191108
TI - A rapid fluorogenic palmitoyl-protein thioesterase assay: pre- and postnatal
diagnosis of INCL.
AB - A deficiency of palmitoyl-protein thioesterase (PPT) was recently shown to be the
primary defect in infantile neuronal ceroid lipofuscinosis (INCL). The available
enzyme assays are complicated and impractical for diagnostic use. We have
recently developed a new, fluorometric assay for PPT based on the sensitive
fluorochrome 4-methylumbelliferone, requiring an overnight incubation to measure
PPT. Now we have synthesized an analogue of this substrate which allows PPT
determinations in 1 h. This improved PPT assay is simple, sensitive, and robust
and will facilitate the definition of the full clinical spectrum associated with
a deficiency of PPT. PPT activity was readily detectable in fibroblasts,
leukocytes, amniotic fluid cells, chorionic villi, plasma, and cerebrospinal
fluid from controls. PPT activity was profoundly deficient in these tissues and
fluids from INCL patients. Similarly, a deficiency of PPT activity was
demonstrated in patients with the variant juvenile NCL with GROD. These results
show the feasibility of rapid pre- and postnatal diagnosis of INCL and its
variants.
PMID- 10191109
TI - The molecular basis of GROD-storing neuronal ceroid lipofuscinoses in Scotland.
AB - Two distinct clinical subtypes of neuronal ceroid lipofuscinosis caused by
mutations in the PPT gene, INCL and vJNCL/GROD, occur at a high frequency in the
central region of Scotland. In this paper we summarize the clinical details and
the molecular basis underlying the disease in the Scottish patients. Comparison
of the combination of mutations in the different clinical types reveals a clear
genotype-phenotype correlation.
PMID- 10191110
TI - Reevaluation of neuronal ceroid lipofuscinoses: atypical juvenile onset may be
the result of CLN2 mutations.
AB - This study describes the phenotype/genotype analyses of 56 probands with a
juvenile onset, some of which had atypical features of neuronal ceroid
lipofuscinosis, collected at the New York State Institute for Basic Research
(IBR). In this group, we found probands with abundant curvilinear profiles in
lysosomal storage material, deficiency of pepstatin-insensitive peptidase, and
mutations in the CLN2 gene, as well as patients with a predominance of granular
osmiophilic deposits in the lysosomal storage material, deficiency of palmitoyl
protein thioesterase, and mutations in the CLN1 gene. We have divided the
probands into two categories: typical (or classic) and atypical. Most of the
typical and atypical probands had onset of symptoms about or after 4 years of
age. Interfamiliar and intrafamiliar variations were found, especially in the
speed of becoming practically blind. Thus, our study indicates that some
mutations in the CLN1, CLN2, and CLN3 genes may be associated with late onset of
the disease process, may have a more benign clinical course, and clinic overlap
with other forms of neuronal ceroid lipofuscinosis.
PMID- 10191111
TI - Intracellular trafficking of the JNCL protein CLN3.
AB - Juvenile neuronal ceroid lipofuscinosis is a lysosomal storage disease that
causes visual impairment, progressive mental deterioration, and eventually death.
A predominant 1.02-kb deletion as well as other mutations have been described in
the CLN3 gene. Lacking significant identity with proteins of known function and
no overt targeting signals within the primary amino acid sequence, accurate
predictions of the intracellular location and function could not be made.
Further, recent conflicting reports identified CLN3 as either a lysosomal or a
mitochondrial protein. Transfection experiments using native and epitope-tagged
fusion proteins were evaluated to help delineate CLN3 localization. We confirmed
by immunohistochemistry and brefeldin A treatment that NH2-terminal green
fluorescence protein (GFP)-CLN3 fusion proteins were retained in the Golgi
apparatus, with no colocalization with mitochondrial markers. Anti-CLN3
antibodies directed against amino acids 67-90 of CLN3 were generated and shown to
be specific for a 50-kDa protein in HEK 293 cells and GFP-CLN3 in transfected
cells. However, cells transfected with nontagged CLN3 or carboxyl-terminal-tagged
CLN3 were not immunoreactive with anti-CLN3 antibodies, suggesting that normally,
the amino terminus interacts with other molecules. Thus, tags on the NH2-terminus
probably inhibited these interactions and movement of CLN3 from the Golgi to more
distal compartments. Also, CLN3 tagged at the COOH-terminus with either GFP or
FLAG epitopes were retained in the ER, indicating a role for the COOH-terminus in
trafficking. Taken together, these data confirm that CLN3 traffics through the ER
and Golgi.
PMID- 10191112
TI - Studies of membrane association of CLN3 protein.
AB - The product of the CLN3 gene is a novel protein of unknown function. Simulations
using amphiphacy algorithms have shown that structurally CLN3 may be another
candidate for the family of membranous proteins. Signals controlling
intracellular targeting of many membrane proteins are present as short sequences
within their cytoplasmic domains. In fact, the sequence of CLN3 protein contains
several such signaling sequences, which are conserved among mammals. First, at
the N-terminus, potential N-myristoylation motif is present. Second, the C
terminal part of CLN3 protein contains both the dileucine motif, which is a
potential lysosomal targeting signal, and the prenylation motif. There is scanty
evidence of lysosomal and/or mitochondrial localization of CLN3 protein. However,
the question of where the functional site of the cln3 protein exists in vivo
remains unanswered. From theoretical calculations, we hypothesized that CLN3
should be an integral part of the membranous micro-environment. First, to test
this hypothesis, we initiated detergent-partitioning experiments, localizing CLN3
predominantly in a pool of membranous protein. Further studies have shown that
CLN3 protein integrates spontaneously with cellular membranes. Second, based on
the prenylation results of CLN3 protein in vitro, we discussed the possible
topological consequences of C-terminal fragment of CLN3 protein.
PMID- 10191113
TI - Analysis of intracellular distribution and trafficking of the CLN3 protein in
fusion with the green fluorescent protein in vitro.
AB - CLN3 gene, associated with juvenile neuronal ceroid lipofuscinosis, encodes a
novel protein of a predicted 438 amino acid residues. We have expressed a full
length CLN3 protein and fragments thereof in fusion with green fluorescent
protein in Chinese hamster ovary and human neuroblastoma cell lines to study its
subcellular localization and intracellular trafficking pattern. By using laser
scanning confocal microscopy, we demonstrate that the full-length CLN3 fusion
protein is targeted to lysosomal compartments. Tunicamycin treatment did not
alter the lysosomal targeting of the CLN3 protein, which indicates that extensive
N-glycosylation of the full-length CLN3 fusion protein is not engaged in its
lysosomal sorting. Monensin produced retention of CLN3 fusion protein in
vesicular structure of the Golgi apparatus in the perinuclear space, suggesting
that CLN3 fusion protein is transported to the lysosomal compartments through the
trans-Golgi cisternae. Neither of the truncated CLN3 fusion proteins encompassing
its 1-138, 1-322, and 138-438 amino acid residues was disclosed in lysosomal
compartments. However, CLN3 fusion protein showing double-point mutations at
amino acid residues 425 and 426, thus at its putative dileucine lysosomal
signaling motif, was still targeted to lysosomes, suggesting that a dileucine
motif alone is not sufficient for lysosomal sorting of the CLN3 fusion protein.
PMID- 10191114
TI - Posttranslational modification of CLN3 protein and its possible functional
implication.
AB - The CLN3 gene associated with Batten disease and encoding a novel protein of a
predicted 438 amino acids was cloned in 1995 by the International Batten Disease
Consortium. The function of CLN3 protein remains unknown. Computer-based analysis
predicted that CLN3 may contain several posttranslational modifications. Thus, to
study the posttranslational modification of CLN3 protein, we have expressed a
full-length CLN3 protein as a C-terminal fusion with green fluorescent protein of
the jellyfish Aequerea victoria in a Chinese hamster ovary cell line. Previously,
we have shown that CLN3 is a glycosylated protein from lysosomal compartment, and
now, by using in vivo labeling with 32P, detection with anti-phosphoamino acid
antibodies, and phosphoamino acid analysis, we demonstrate that CLN3 is a
phosphorylated protein. We demonstrate that CLN3 protein does not undergo mannose
6-phosphate modification and that it is a membrane protein. Furthermore, we show
that the level of CLN3 protein phosphorylation may be modulated by several
protein kinases and phosphatases activators or inhibitors.
PMID- 10191115
TI - Expression studies of CLN3 protein (battenin) in fusion with the green
fluorescent protein in mammalian cells in vitro.
AB - The gene for Batten disease, the CLN3 gene, encodes a novel, highly hydrophobic,
multitransmembrane protein, predicted to consist of 438 amino acid residues. We
have expressed a full-length CLN3 protein in fusion with green fluorescent
protein in various cell lines to provide its initial biochemical characterization
and subcellular localization. By using Western blotting, Percoll density gradient
fractionation, and Triton X-114 extraction, we demonstrate that the product of
the CLN3 gene, which we call battenin, in mammalian expression system studied is
a highly glycosylated protein of lysosomal membrane. In addition our data suggest
that CLN3 protein is processed proteolytically in acidic compartments of the
cell. Thus, battenin represents the novel constituent of a growing family of
lysosomal membrane proteins.
PMID- 10191116
TI - Tissue expression and subcellular localization of CLN3, the Batten disease
protein.
AB - Juvenile neuronal ceroid lipofuscinosis (Batten disease) is a progressive
neurologic disorder which results from mutations in the CLN3 gene, which normally
produces a 48-kDa polypeptide of unknown function. To help characterize the CLN3
protein, we have studied its tissue distribution and subcellular localization in
human tissues using three epitope-specific polyclonal antibodies to human CLN3 by
immunoblot, immunocytochemical, and immunoelectron microscopic analysis. The most
abundant CLN3 protein expression was in the gray matter of the brain, where it
was localized to astrocytes, capillary endothelium, and neurons. CLN3 was also
evident in peripheral nerve, in pancreatic islet cells, and within the
seminiferous tubules in the testis. Staining was generally diffuse within the
cytoplasm with some nuclear reactivity. Subcellular localization identified the
CLN3 protein within the nucleus and along cell membranes. These results were
contrasted with the cellular distribution of palmitoyl-protein thioesterase
(PPT), the enzyme whose deficiency is responsible for infantile neuronal ceroid
lipofuscinosis (CLN1). PPT was most abundant in brain and visceral macrophages
where it displayed a coarse granular staining pattern typical of lysosomal
distribution. Immunoelectron microscopy confirmed that PPT immunoreactivity was
limited to lysosomes.
PMID- 10191117
TI - The expression of palmitoyl-protein thioesterase is developmentally regulated in
neural tissues but not in nonneural tissues.
AB - Mutations in a palmitoyl-protein thioesterase (PPT) gene cause infantile neuronal
ceroid lipofuscinosis (INCL). INCL is characterized by an extreme and selective
neuronal loss in cerebral cortex and retina. Using reverse transcriptase PCR we
show that PPT expression is developmentally regulated in rat brain and eyes but
not in spleen. The changes in the expression coincide with developmental events
in the brain. These data indicate that PPT has an important role in the
development of the CNS.
PMID- 10191118
TI - CLN3 defines a novel antiapoptotic pathway operative in neurodegeneration and
mediated by ceramide.
AB - Juvenile neuronal ceroid lipofuscinosis or Batten disease (JNCL) is a
neurodegenerative disorder characterized by blindness, seizures, cognitive
decline and early death. Brain atrophy and retinitis pigmentosa ensue because of
neuronal and photoreceptor apoptosis. The CLN3 gene defective in JNCL encodes a
novel 438 amino acid protein. Most affected genes harbor a deletion resulting in
a truncated protein. CLN3 overexpression in NT2 cells enhances growth, reverses
growth inhibition induced by serum starvation and protects from apoptosis induced
by vincristine, staurosporine, and etoposide but not from death caused by
ceramide. CLN3 modulates endogenous and vincristine-activated ceramide, and
therefore suppresses apoptosis by impacting generation of ceramide.
PMID- 10191119
TI - A murine model for juvenile NCL: gene targeting of mouse Cln3.
AB - JNCL is a neurodegenerative disease of childhood caused by mutations in the CLN3
gene. A mouse model for JNCL was created by disrupting exons 1-6 of Cln3,
resulting in a null allele. Cln3 null mice appear clinically normal at 5 months
of age; however, like JNCL patients, they exhibit intracellular accumulation of
autofluorescent material. A second approach will generate mice in which exons 7
and 8 of Cln3 are deleted, mimicking the common mutation in JNCL patients.
PMID- 10191120
TI - Investigation of Batten disease with the yeast Saccharomyces cerevisiae.
AB - The CLN3 gene, which encodes the protein whose absence is responsible for Batten
disease, the most common inherited neurovisceral storage disease of childhood,
was identified in 1995. The function of the protein, Cln3p, still remains
elusive. We previously cloned the Saccharomyces cerevisiae homolog to the human
CLN3 gene, designated BTN1, whose product is 39% identical and 59% similar to
Cln3p. We report that yeast strains lacking Btn1p, btn1-Delta deletion yeast
strains, are more resistant to d-(-)-threo-2-amino-1-[p-nitrophenyl]-1,3
propanediol (ANP), in a pH-dependent manner. This phenotype is complemented in
yeast by the human CLN3 gene. In addition, point mutations characterized in CLN3
from individuals with less severe forms of Batten disease, when introduced into
BTN1, altered the degree of ANP resistance. Severity of Batten disease due to
mutations in CLN3 and the degree of ANP resistance in yeast are related when the
equivalent amino acid replacements in Cln3p and Btn1p are compared. These results
indicate that yeast can be used as a model for the study of Batten disease.
PMID- 10191121
TI - Studies of pH regulation by Btn1p, the yeast homolog of human Cln3p.
AB - Although the gene responsible for Batten disease, CLN3, was positionally cloned
in 1995, the function of Cln3p and the molecular basis of the disease still
remain elusive. We previously reported that the yeast Saccharomyces cerevisiae
contains a homolog to Cln3p, designated Btn1p, and that the human Cln3p
complemented the pH-dependent resistance to D-(-)-threo-2-amino-1-[p-nitrophenyl]
1, 3-propanediol in btn1-Delta yeast mutants. We have determined that yeast
lacking Btn1p have an elevated ability to acidify media during growth that
correlates with an elevated plasma membrane ATPase activity. Btn1p may be
involved in maintaining pH homeostasis of yeast cells.
PMID- 10191122
TI - Positional cloning of the CLN5 gene defective in the Finnish variant of the
LINCL.
AB - Neuronal ceroid lipofuscinoses (NCLs) in children are progressive
encephalopathies inherited as autosomal recessive traits. Progressive neuronal
damage leads to psychomotor deterioration, visual failure, seizures, and finally
to premature death. Based on the clinical course of the disease, the childhood
forms can be divided into several subtypes. A variant form of the late infantile
NCL (vLINCL), characterized by mental retardation, visual failure, ataxia,
myoclonia, and death between the ages of 13 and 30 years, is prevalent in
Finland. Information on ancient recombination events in disease alleles rising
from this isolated population provided an efficient tool for refining the initial
assignment of the CLN5 locus. Here we describe the steps resulting in the
identification of the novel gene, defective in vLINCL.
PMID- 10191123
TI - Genetic and physical mapping of the CLN6 gene on chromosome 15q21-23.
AB - CLN6, the gene for a variant late infantile neuronal ceroid lipofuscinosis, has
been mapped to chromosome 15q21-23 by homozygosity mapping. At present the family
resource consists of 31 families. By the analysis of additional polymorphic
markers in this resource the critical region has been narrowed down from 12 cM to
less than 4 cM. A physical map is being constructed using YAC and PAC clones as a
prerequisite to transcript mapping.
PMID- 10191124
TI - Progress toward the cloning of CLN6, the gene underlying a variant LINCL.
AB - Marked clinical heterogeneity is seen in the late-infantile subtype of NCL
(LINCL), complicating genetic analysis. In addition to the classical subtype,
encoded by CLN2 on chromosome 11p15.5, several variant subtypes have also been
described. In this paper, we report our progress in cloning a variant LINCL gene
mapped in a small group of Costa Rican families. Clinically, these patients
appear similar to classical LINCL patients, except onset of the disease is
delayed and the course is milder. Extended haplotype analysis confirms the
localization of this gene to chromosome 15q21-22, where CLN6 has also been
mapped. Using now-standard positional cloning techniques, we have developed a
physical map of our candidate region. These clones have been used to order
genetic markers, STSs, and ESTs in this region and will be used for the
identification of the disease gene transcript.
PMID- 10191125
TI - A new locus for variant late infantile neuronal ceroid lipofuscinosis-CLN7.
AB - To date two genes are known to be involved in variant LINCL, CLN5 and CLN6, which
map to chromosomes 13q21 and 15q21-23. A subset of Turkish families with a
variant phenotype has been identified. Affected individuals have curvilinear
bodies and fingerprint profiles on EM but are recombinant at CLN5 and CLN6. These
families appear to represent a new locus. Homozygosity mapping is being used to
map this locus, which has been designated CLN7.
PMID- 10191126
TI - Genetic heterogeneity of neuronal ceroid lipofuscinosis in The Netherlands.
AB - An overview of patients in the Netherlands who are known to us with neuronal
ceroid lipofuscinosis (NCL) is presented. Several CLN genes involved in NCL have
been isolated or mapped. We have analyzed families with different types of NCL
with polymorphic markers linked to CLN loci to investigate the genetic
heterogeneity of NCL in the Netherlands. Haplotype analysis suggests that in
addition to the CLN2 and CLN6 genes another gene is involved in at least one
family with late infantile NCL in the Netherlands. The CLN2 and CLN6 loci have
also been excluded in a family with protracted juvenile NCL.
PMID- 10191127
TI - Clinical and molecular analysis of Japanese patients with neuronal ceroid
lipofuscinosis.
AB - Neuronal ceroid lipofuscinosis (NCL) is one of the most common inherited
neurological diseases in childhood. It occurs every 12,500 births in northern
European populations. Mental retardation, visual impairment, and seizures are
common symptoms. The prevalence of NCL is variable depending upon the races or
countries. Although a wealth information is available in Caucasian populations,
there is little information about NCL in Asian people. Because a nationwide
survey in Japanese patients with NCL has never been performed, we pursued an
epidemiological survey. We identified 36 NCL patients in Japan. Patients with
infantile, late infantile, juvenile, and adult type accounted for 2, 15, 15, and
4 cases, respectively. Seizures were a major initial symptom in the late
infantile type. In the juvenile type, visual failure was present in 73% at onset.
Recently, the juvenile NCL (Batten disease) gene has been isolated. Studies of
the mutations in this gene demonstrated that a 1.02-kb deletion was the most
prevalent mutation among Caucasian patients, accounting for 81% of total alleles.
To determine the prevalence of this 1.02-kb deletion in Japanese patients, we
performed a rapid allele-specific polymerase chain reaction test. No 1.02-kb
major deletion was detected in 5 Japanese juvenile NCL cases. These data suggest
that the distribution of NCL and clinical findings are similar to those of
Caucasian subjects; however, prevalence of mutations in Japanese patients with
NCL would be distinct from that observed in Caucasians.
PMID- 10191128
TI - Anomalies of mitochondrial ATP synthase regulation in four different types of
neuronal ceroid lipofuscinosis.
AB - Several neuronal ceroid lipofuscinoses (NCL) show storage of subunit c of
mitochondrial ATP synthase. The neurodegenerative process, however, remains
obscure. We previously reported a decreased basal ATP synthase activity in
fibroblasts from late-infantile NCL (CLN2) and juvenile NCL (CLN3) patients. We
have now extended the study of the ATP synthase system to an ovine NCL (a model
for the late-infantile NCL variant, CLN6) and the infantile NCL (CLN1). In
fibroblasts from healthy sheep, active regulation of ATP synthase in response to
cellular energy demand was present similar to human cells: ATP synthase was down
regulated under conditions of anoxia or functional uncoupling and was up
regulated in response to calcium. In fibroblasts from NCL sheep, basal ATP
synthase activity was slightly elevated and down-regulation in response to anoxia
or uncoupling of mitochondria also occurred. Calcium produced an unexpected down
regulation to 55% of basal activity. Activities of respiratory chain enzymes did
not differ between healthy and NCL sheep. In fibroblasts from CLN1 patients,
basal ATP synthase activity was reduced and regulation of the enzyme was absent.
Activities of respiratory chain complexes II and IV were reduced. The defect of
ATP synthase regulation found in fibroblasts from NCL sheep and infantile NCL
patients is different from the ATP synthase deficiencies demonstrated in late
infantile and juvenile NCL, but problems of mitochondrial energy production, if
also expressed in brain, would be a common feature of several NCL forms.
Deficient ATP supply could result in degeneration of neurons, especially in those
with high energy requirements.
PMID- 10191129
TI - Retinal degeneration in retinitis pigmentosa and neuronal ceroid lipofuscinosis:
An overview.
AB - Retinal degeneration is an early consequence of the group of lysosomal storage
diseases collectively referred to as the neuronal ceroid lipofuscinoses (NCLs).
This review details specialized techniques that have evolved for retinal
assessment in patients with hereditary retinal degeneration. A standard ERG
protocol is described for assessing rod- and cone-mediated function.
Standardization will be crucial for planning and implementing multicenter trials
as rational therapeutic intervention becomes available. In recent years, there
has been a dramatic increase in knowledge of the molecular biological bases of
retinitis pigmentosa and allied retinal degenerations. Rather than attempting a
comprehensive summary, this review stresses the concepts of genetic, allelic, and
clinical heterogeneity, which have obvious parallels in the NCLs. Many of the
mutations that cause retinal degeneration are in genes that encode photoreceptor
cascade proteins; others are in genes that encode photoreceptor structural
proteins. Recent advances in linking the retinal degeneration slow (RDS) and ATP
binding cassette transporter retina (ABCR) genes to a variety of disease
phenotypes will be summarized. Clinical heterogeneity even among family members
with the same mutation raises the possibility that modifying factors, either
genetic or environmental, could influence the severity of the disease. Here, we
focus on vitamin A and docosahexaenoic acid, two potential nutritional modifiers
that have received considerable attention in recent years.
PMID- 10191130
TI - Progress in neuropathology of the neuronal ceroid lipofuscinoses.
AB - Since the last, 6th, International Congress on Neuronal Ceroid-Lipofuscinoses,
neuropathological advances in neuronal ceroid lipofuscinoses (NCL) have been made
in several areas: (1) In adult NCL (ANCL) lipopigments have now been repeatedly
confirmed to contain subunit c of mitochondrial ATP synthase and even
sphingolipid activators (saposins). ANCL lipopigments have also been confirmed in
extracerebral tissues including skin, skeletal muscle, and spleen, but not yet
lymphocytes (2). Among circulating blood cells not only B cells and subclasses of
T lymphocytes, i.e., CD4(+), CD8(+), and CD56 cells, but also monocytes have been
found to contain NCL lipopigments, indicating that this precursor cell in the
digesting macrophage system also has an impaired metabolic catabolism for
lipopigments (3). Immunohistochemical studies indicate that microglial reaction
in NCL brain is limited to resident microglia without contribution by circulating
monocytes (4). The granular osmiophilic deposit (GROD) type of NCL has now been
established not only in infantile, but also in late-infantile, juvenile, and
protracted-juvenile NCL (5). A European Tissue Registry established within the
framework of a European Concerted Action on Neuronal Ceroid-Lipofuscinosis may
form the basis for additional collaborative studies on NCL, including both biopsy
and autopsy tissues.
PMID- 10191132
TI - Ovine ceroid lipofuscinosis (OCL6): postulated mechanism of neurodegeneration.
AB - It is proposed that ceroid lipofuscinosis in Southhampshire sheep
(OCLSouthhampshire) be also known as OCL6 as it is syntenic with CLN6 of humans.
Histopathological studies show a severe and progressive neurodegeneration of the
cerebral cortex which sometimes appears to have a laminar pattern and which is
accompanied by a severe midcortical astrocytosis. Other studies have shown that
fibroblasts maintained in tissue culture have abnormal regulation of ATP
synthase. If this was reflected in neurons, then selective neuron death is likely
to be the result of energy-linked excitotoxicity of neurons receiving abundant
glutamate input. Increased sensitivity of the NMDA receptor due to inefficient
repolarization of the neuron membrane would allow increased cellular uptake of
calcium, increased formation of free radicals, and neuron death. The general
hypothesis, as developed for other chronic neurodegenerative diseases, is partly
based on application of various drugs that block or mediate parts of the pathway
involved. The same approach could be used to help test the hypothesis in OCL6
lambs and if successful some of the drugs might have therapeutic potential. As
patterns of neurodegeneration are similar in various other forms of ceroid
lipofuscinosis accumulating subunit c of mitochondrial ATP synthase, the model
may have more general application than merely to CLN6.
PMID- 10191131
TI - Progress toward positional cloning of ovine neuronal ceroid lipofuscinosis, a
model of the human late-infantile variant CLN6.
AB - The neuronal ceroid lipofuscinoses (NCLs) are lysosomal storage diseases with
severe neurodegenerative pathology. An ovine model (OCL) has well-defined
parallels with the human disease at the biochemical and pathological levels. The
gene for OCL is located in the chromosomal region OAR7q13-15. This region is
syntenic with HAS15q21-23, suggesting that OCL and CLN6 represent mutations in
orthologous genes. New microsatellite markers have been developed enabling
further refinement of the OCL critical region.
PMID- 10191133
TI - Disease-specific pathology in neurons cultured from sheep affected with ceroid
lipofuscinosis.
AB - The neuronal ceroid lipofuscinoses (NCL, Batten disease) are a group of inherited
neurodegenerative storage diseases in children. Mutations in different genes
underlie different forms. Subunit c of mitochondrial ATP synthase is specifically
stored in autofluorescent bodies in most of them, including a form in sheep.
Mature bodies are lysosomal but the initial site of storage is not known, nor is
it known how this leads to the characteristic neurodegeneration. Neurons were
cultured in serum-free medium from control and affected sheep fetuses at 90 days
gestation. They showed positive microtubule-associated protein staining,
developed neurites, and had typical neuron morphology. Time-dependent
accumulation of subunit c and of fluorescent storage bodies was observed in
affected cells by immunocytochemistry and confocal microscopy. A small number of
autofluorescent bodies were apparent after 4 days in culture. After 10 days these
bodies were more numerous, more intensely autofluorescent, and often larger in
size. By 14 and 21 days many neurons were packed with autofluorescent material.
These bodies were not seen in control cultures. Immunocytochemistry revealed
subunit c-positive storage material only in affected neurons and not in affected
glial cells. Confocal microscope analysis, using organelle-specific dyes,
demonstrated colocalization of autofluorescent bodies with lysosomes, not with
mitochondria. Survival rates of the affected cells were unaffected by the storage
body accumulation over a 3-month period. These cultures can now be used to study
the mechanism of subunit c accumulation and of neurodegeneration and to test
therapeutic possibilities.
PMID- 10191134
TI - Ion pores made of mitochondrial ATP synthase subunit c in the neuronal plasma
membrane and Batten disease.
AB - A hypothesis is outlined that the neurodegeneration of the Batten disease
syndromes that involve an overaccumulation of subunit c is caused by a newly
characterized function of the protein, its ability to assemble in the plasma
membrane into ion pores (J. E. M. McGeoch and G. Guidotti, Brain Res 766: 188
194, 1997), rendering the cell liable to constant electrical excitability to a
degree that causes cell death.
PMID- 10191135
TI - An early-onset congenic strain of the motor neuron degeneration (mnd) mouse.
AB - The mouse mutant motor neuron degeneration (mnd/mnd) has been proposed as a model
of neuronal ceroid lipofuscinosis (NCL) on the basis of widespread abnormal
accumulating lipopigment and neuronal and retinal degeneration. Clinically, the
mutant on a C57Bl/6 genetic background shows a progressive motor abnormality
starting by 6 months of age, with death prior to 12 months. When mnd is
outcrossed to the AKR/J genetic background, ca. 40% of the mnd/mnd F2 progeny
show early onset (onset by 4.5-5 months and death by 7 months). A congenic strain
of mnd has now been produced by eight generations of backcross onto the AKR
background. Mice on this background show average onset at 4 months, and most are
moribund prior to 5.5 months. The early onset appears to correlate with levels of
abnormal accumulating material, and should prove useful in elucidating NCL
neurodegenerative mechanisms.
PMID- 10191136
TI - Ultrastructural and electrophysiological correlation of the genotypes of NCL.
AB - Several genetically different, but clinically similar childhood forms of neuronal
ceroid lipofuscinosis are now recognized. Accurate diagnosis is important so that
appropriate genetic advice can be given, molecular analysis can be undertaken,
and prenatal testing can be considered. A combined clinical,
electrophysiological, and histological (light and electron microscopy) approach
offers the most reliable means of diagnosis in the majority of patients. Patients
with an unusual presentation will also be identified.
PMID- 10191138
TI - The European Concerted Action NCL Clinical Case Registry.
AB - A European NCL Clinical Case Registry has been set up in London, as part of a
European Union-funded Concerted Action project. Concerted Action participants
provide written information about children which is then anonymized and entered
on the Registry. Contributors are able to request information contained within
the Registry for the purpose of epidemiological, molecular, diagnostic, or
therapeutic research. Up to May 1998, 60 cases were entered on the Registry.
PMID- 10191137
TI - Melatonin ineffective in neuronal ceroid lipofuscinosis patients with fragmented
or normal motor activity rhythms recorded by wrist actigraphy.
AB - Melatonin was tested as a sleeping pill in five patients with neuronal ceroid
lipofuscinoses. The single-blind, placebo-controlled study consisted of motor
activity recordings, sleep logs, and administration of placebo or melatonin (2.5
or 5 mg). Daily motor activity rhythms were measured by wrist actigraphy during
four 7-day periods (baseline, placebo, melatonin 2.5 mg, and melatonin 5 mg). The
placebo or melatonin was administered in the evenings for 3 weeks, and the
recordings were made during the last week of the 3-week treatment. Sleep logs
were kept by the caregivers during the recordings. Based on period analyses, the
activity recordings were evaluated to display a normal (24-h) or fragmented
rhythm. Three patients had normal motor activity patterns during the baseline
recordings, and administration of placebo or melatonin did not affect their
rest/activity rhythms. Two patients had abnormally fragmented activity rhythms
during the baseline periods, and administration of placebo or melatonin did not
induce synchronization. According to the actigraphic data, there were no changes
in activity rhythms resulting from administration of melatonin. However, based on
the observations, three families reported that melatonin slightly improved the
sleep quality of the patients. These controversial findings show the difficulties
involved in specifying the role of melatonin in modulating sleep. Thus, we
conclude that more evidence is required before the significance of melatonin as a
sleeping pill is defined.
PMID- 10191139
TI - The 2.2 A crystal structure of human chymase in complex with succinyl-ala-ala-pro
phe-chloromethylketone: structural explanation for its dipeptidyl
carboxypeptidase specificity
PMID- 10191140
TI - Structure of active site carboxymethylated D-glyceraldehyde-3-phosphate
dehydrogenase from Palinurus versicolor.
AB - The structure of active site carboxymethylated D-glyceraldehyde-3-phosphate
dehydrogenase from Palinurus versicolor was determined in the presence of
coenzyme NAD+ at 1.88 A resolution with a final R-factor of 0.175. The structure
refinement was carried out on the basis of the structure of holo-GAPDH at 2.0 A
resolution using the program XPLOR. The carboxymethyl group connected to Cys149
is stabilized by a hydrogen bond between its OZ1 and Cys149N, and charge
interaction between the carboxyl group and the nicotinamide moiety. The
modification of Cys149 induced conformational changes in the active site, in
particular, the site of sulphate ion 501 (the proposed attacking inorganic
phosphate ion in catalysis), and segment 208-218 nearby. Extensive hydrogen
bonding interactions occur in the active site, which contribute to the higher
stability of the modified enzyme. The modification of the active site did not
affect the conformation of GAPDH elsewhere, including the subunit interfaces. The
structures of the green and red subunits in the asymmetric unit are nearly
identical, suggesting that the half-site reactivity of this enzyme is from ligand
induced rather than pre-existing asymmetry. It is proposed that the carboxymethyl
group takes the place of the acyl group of the reaction intermediate, and the
catalytic mechanism of this enzyme is discussed in the light of a comparison of
the structures of the native and the carboxymethylated GAPDH.
PMID- 10191141
TI - Selection of cleavage site by mammalian tRNA 3' processing endoribonuclease.
AB - Mammalian tRNA 3' processing endoribonuclease (3' tRNase) removes 3' trailers
from pre-tRNAs by cleaving the RNA immediately downstream of the discriminator
nucleotide. Although 3' tRNase can recognize and cleave any target RNA that forms
a pre-tRNA-like complex with another RNA, in some cases cleavage occurs at
multiple sites near the discriminator. We investigated what features of pre-tRNA
determine the cleavage site using various pre-tRNAArg variants and purified pig
enzyme. Because the T stem-loop and the acceptor stem plus a 3' trailer are
sufficient for recognition by 3' tRNase, we constructed variants that had
additions and/or deletions of base-pairs in the T stem and/or the acceptor stem.
Pre-tRNAs lacking one and two acceptor stem base-pairs were cleaved one and two
nucleotides and two and three nucleotides, respectively, downstream of the
discriminator. On the other hand, pre-tRNA variants containing extra acceptor
stem base-pairs were cleaved only after the discriminator. The cleavage site was
shifted to one and two nucleotides downstream of the discriminator by deleting
one base-pair from the T stem, but was not changed by additional base-pairs in
the T stem. Pre-tRNA variants that contained an eight base-pair acceptor stem
plus a six base-pair T stem, an eight base-pair acceptor stem plus a four base
pair T stem, or a six base-pair acceptor stem plus a six base-pair T stem were
all cleaved after the original nucleotide. In general, pre-tRNA variants
containing a total of more than 11 bp in the acceptor stem and the T stem were
cleaved only after the discriminator, and pre-tRNA variants with a total of N bp
(N is less than 12) were cleaved 12-N and 13-N nt downstream of the
discriminator. Cleavage efficiency of the variants decreased depending on the
degree of structural changes from the authentic pre-tRNA. This suggests that the
numbers of base-pairs of both the acceptor stem and the T stem are important for
recognition and cleavage by 3' tRNase.
PMID- 10191142
TI - Calcium-mediated structural changes of native nuclear pore complexes monitored by
time-lapse atomic force microscopy.
AB - Nuclear pore complexes (NPCs) are large macromolecular assemblies embedded in the
double membrane nuclear envelope. They are the major gateways mediating transport
of ions, small molecules, proteins, RNAs, and ribonucleoprotein particles in and
out of the nucleus in interphase cells. Understanding structural changes at the
level of individual pores will be a prerequisite to eventually correlate the
molecular architecture of the NPC with its distinct functional states during
nucleocytoplasmic transport. Toward this goal, we have employed time-lapse atomic
force microscopy of native NPCs kept in buffer, and recorded calcium-mediated
structural changes such as the opening (i.e. +Ca2+) and closing (i.e. -Ca2+) of
individual nuclear baskets. Most likely, this structural change of the nuclear
basket involves its distal ring which may act as an iris-like diaphragm. In order
to directly correlate distinct structural features with corresponding functional
states and dynamic aspects, we also addressed the question of whether the
"central plug" or "transporter" actually represents a calcium-sensitive component
of the NPC involved in mediating nucleocytoplasmic transport. Our data indicate
that in the absence of ATP, cytoplasmic plugging/unplugging of the NPC is
insensitive to calcium.
PMID- 10191144
TI - Structure and mechanism of the amphibolic enzyme D-ribulose-5-phosphate 3
epimerase from potato chloroplasts.
AB - Ribulose-5-phosphate 3-epimerase (EC 5.1.3.1) catalyzes the interconversion of
ribulose-5-phosphate and xylulose-5-phosphate in the Calvin cycle and in the
oxidative pentose phosphate pathway. The enzyme from potato chloroplasts was
expressed in Escherichia coli, isolated and crystallized. The crystal structure
was elucidated by multiple isomorphous replacement and refined at 2.3 A
resolution. The enzyme is a homohexamer with D3 symmetry. The subunit chain fold
is a (beta alpha)8-barrel. A sequence comparison with homologous epimerases
outlined the active center and indicated that all members of this family are
likely to share the same catalytic mechanism. The substrate could be modeled by
putting its phosphate onto the observed sulfate position and its epimerized C3
atom between two carboxylates that participate in an extensive hydrogen bonding
system. A mutation confirmed the crucial role of one of these carboxylates. The
geometry together with the conservation pattern suggests that the negative charge
of the putative cis-ene-diolate intermediate is stabilized by the transient
induced dipoles of a methionine sulfur "cushion", which is proton-free and
therefore prevents isomerization instead of epimerization.
PMID- 10191143
TI - RNA polymerase subunit H features a beta-ribbon motif within a novel fold that is
present in archaea and eukaryotes.
AB - The archaeal H and eukaryotic RPB5 RNA polymerase subunits are highly homologous
and are likely to play a fundamental role in transcription that extends from
archaea to humans. We report the structure of subunit H, in solution, from the
archaeon Methanococcus jannaschii using multidimensional nuclear magnetic
resonance. The structure reveals a novel fold containing a four-stranded mixed
beta sheet that is flanked on one side by three short helices. The dominant
feature is beta-ribbon motif, which presents a hydrophobic, basic surface, and
defines a general RNA polymerase architectural scaffold.
PMID- 10191145
TI - Structural features of the interaction between an anti-clonotypic antibody and
its cognate T-cell antigen receptor.
AB - The crystal structure of the complex between a single chain Fv fragment of the
KB5-C20 T-cell antigen receptor (TCR) and the specific anti-clonotypic antibody
(Ab) Desire-1 provides the first description of the interface between a clonotype
and an anti-clonotype. In the four idiotype/anti-idiotype complexes of known
three-dimensional structures, the interacting Fv fragments associate largely
through their complementarity-determining regions (CDRs). In marked contrast,
Desire-1 binds to a face of the KB5-C20 TCR that is almost perpendicular to the
TCR antigen binding site, and recognizes discontinuous stretches of TCR Valpha
and Vbeta residues that belong to both the CDRs and the framework. Despite this
peculiar mode of interaction, Desire-1 constitutes a genuine anti-clonotypic Ab.
Moreover, in spite of the fact that the Desire-1 contact residues do not
constitute a molecular mimic of the physiological ligand normally recognized by
the KB5-C20 TCR, the bivalent Desire-1 Ab is capable of efficiently activating T
cells expressing the KB5-C20 TCR.
PMID- 10191147
TI - GenTHREADER: an efficient and reliable protein fold recognition method for
genomic sequences.
AB - A new protein fold recognition method is described which is both fast and
reliable. The method uses a traditional sequence alignment algorithm to generate
alignments which are then evaluated by a method derived from threading
techniques. As a final step, each threaded model is evaluated by a neural network
in order to produce a single measure of confidence in the proposed prediction.
The speed of the method, along with its sensitivity and very low false-positive
rate makes it ideal for automatically predicting the structure of all the
proteins in a translated bacterial genome (proteome). The method has been applied
to the genome of Mycoplasma genitalium, and analysis of the results shows that as
many as 46 % of the proteins derived from the predicted protein coding regions
have a significant relationship to a protein of known structure. In some cases,
however, only one domain of the protein can be predicted, giving a total coverage
of 30 % when calculated as a fraction of the number of amino acid residues in the
whole proteome.
PMID- 10191146
TI - Conformational transitions of islet amyloid polypeptide (IAPP) in amyloid
formation in vitro.
AB - Amyloid aggregates have been recognized to be a pathological hallmark of several
fatal diseases, including Alzheimer's disease, the prion-related diseases, and
type II diabetes. Pancreatic amyloidosis is characterized by the deposition of
amyloid consisting of islet amyloid polypeptide (IAPP). We followed the steps
preceding IAPP insolubilization and amyloid formation in vitro using a variety of
biochemical methods, including a filtration assay, far and near-UV circular
dichroism (CD) spectropolarimetry, 1-anilino-8-naphthalenesulfonic acid (ANS)
binding, and atomic force (AFM) and electron (EM) microscopy. IAPP
insolubilization and amyloid formation followed kinetics that were consistent
with the nucleation-dependent polymerization mechanism. Nucleation of IAPP
amyloid formation with traces of preformed fibrils induced a rapid conformational
transition into beta-sheets that subsequently aggregated into insoluble amyloid
fibrils. Transition proceeded via a molten globule-like conformeric state with
large contents of secondary structure, fluctuating tertiary and quaternary
aromatic interactions, and strongly solvent-exposed hydrophobic patches. In the
temperature denaturation pathway at 5 microM peptide, we found that this state
was mostly populated at about 45 degrees C, and either aggregated rapidly into
amyloid by prolonged exposure to this temperature, or melted into denaturated but
still structured IAPP, when heated further to 65 degrees C. The state at 45
degrees C was also found to be populated at 4.25 M GdnHCl at 25 degrees C during
GdnHCl-induced equilibrium denaturation, and was stable in solution for several
hours before aggregating into amyloid fibrils. Our studies suggested that this
amyloidogenic state was a self-associated form of an aggregation-prone, partially
folded state of IAPP. We propose that this partially folded population and its
self-associated forms are in a concentration-dependent equilibrium with a non
amyloidogenic IAPP conformer and may act as early, soluble precursors of beta
sheet and amyloid formation. Our findings on the molecular mechanism of IAPP
amyloid formation in vitro should assist in gaining insight into the pathogenesis
and inhibition of pancreatic amyloidosis and other amyloid-related diseases.
PMID- 10191148
TI - The Rotational Spectrum of the p-Fluorotoluene- Argon van der Waals Complex.
AB - The microwave rotational spectrum of the p-fluorotoluene-argon van der Waals
complex was analyzed with a molecular beam Fourier transform microwave
spectrometer. In the frequency splitting of molecular transitions caused by the
internal rotation of the methyl group with respect to the aromatic ring is
contained the structure and barrier information. Elucidation is reduced by the
analysis of internal rotors direction with respect to the principal axis system
of the complex the number of possible solutions in the structure. An rs and r0
structure of the complex was calculated from these data. The argon is located
3.541(1) A above the aromatic ring. By forming the complex, the barrier height of
internal rotation is changed. An additional V3 term in the potential function
occurs in the complex because the molecular symmetry of the p-fluorotoluene,
containing a V6 but no V3 term, is reduced by the argon. For assumed V6 =
144.79(19) GHz or 57.777(76) J/mol, V3 is found to equal 552.0(10) GHz or
220.31(40) J/mol. Copyright 1999 Academic Press.
PMID- 10191149
TI - Laser-Excited Fluorescence Spectra of Strontium Monoiodide.
AB - Fluorescence spectra of strontium monoiodide excited by Ar++ and Kr+ laser lines
have been analyzed by Fourier transform spectrometry. Rotational levels have been
populated either directly or after collisional relaxation: (i) in D2Sigma+ (v =
0, 1) by ultraviolet lines of Ar++, inducing numerous fluorescence transitions
ending in the levels v = 0-3 of the strongly interacting A2Pi and B2Sigma+
states, (ii) in A2Pi3/2 (v = 0-4) by Kr+ line at 676.44 nm, de-exciting into
transitions to X2Sigma+ (v = 0-6). Deperturbed constants for A2Pi and B2Sigma+
states and A approximately B interaction parameter are calculated from the
numerical treatment of D2Sigma+ (v = 0, 1) --> A2Pi (v = 0-3) approximately
B2Sigma+ (v = 0-3) transitions. Rotational constants for D2Sigma+ (v = 0, 1) are
obtained for the first time. The wavenumbers of some 670 fluorescence lines are
cataloged. Copyright 1999 Academic Press.
PMID- 10191150
TI - Analysis of Rovibrational Resonances Observed in the Microwave Spectrum of FCCCN.
AB - Microwave spectrum of fluorocyanoacetylene (FCCCN) produced by a glow discharge
in pentafluorobenzonitrile (C6F5CN) was observed using a source modulation
spectrometer with a free-space absorption cell. Rotational transitions in the
range from J = 9-8 to 53-52 were observed for the vibrationally excited states of
nu4 (C&sbond;C stretch), nu5 (CCN bend), nu6 (FCC bend), nu7 (CCC bend), and
their associated overtone and combination states up to about 1000 cm-1. Most of
the vibrational states above 500 cm-1 are perturbed by rovibrational resonances.
The effective vibration-rotation constant of the nu4 state has a negative value (
0.4 MHz), although a vibration-rotation constant generally has a positive value
in the excited state of the stretching vibrational mode in a linear molecule.
This anomalous behavior is interpreted as due to the rovibrational resonances
between the nu4 and several nearby states. By the simultaneous analysis of the
states concerned, the unperturbed vibrational energy and rotational constant of
the nu4 state are obtained to be 686.50(76) cm-1 and 2068.2387(21) MHz,
respectively, where the uncertainties correspond to one standard deviation.
Copyright 1999 Academic Press.
PMID- 10191151
TI - The Far-Infrared Laser Magnetic Resonance Spectrum of CH2F.
AB - Far-infrared laser magnetic resonance (FIR-LMR) spectra due to the CH2F radical
have been recorded on seven laser lines at wavelengths between 301 and 568 um.
Observed resonances were assigned to fine and hyperfine components of pure
rotational transitions of CH2F in the ground vibrational state and the first
excited state of the nu4 out-of-plane bending mode. All assigned transitions obey
a-dipole selection rules. The data were combined with previously reported
microwave results (Y. Endo, C. Yamada, S. Saito, and E. Hirota, J. Chem. Phys.
79, 1605 (1983)) and subjected to a least-squares fit to determine the parameters
of the effective Hamiltonian describing the v4 = 0 and 1 vibrational levels of
the CH2F radical. Copyright 1999 Academic Press.
PMID- 10191152
TI - High-Lying Rotational Levels of Water: Comparison of Calculated and Experimental
Energy Levels for (000) and (010) up to J = 25 and 21.
AB - Emission spectra of methane-oxygen low-pressure flames have been recorded at a
resolution of 0.02 cm-1 with an infrared Fourier transform spectrometer in the
spectral ranges 780-1370 and 1800-5000 cm-1. The flame temperature was about 1850
K and a large number of transitions involving J values as high as 34 for an
extended set of vibrational states could be assigned. Combined with already
published data sets on H2O, our line position analysis yielded rotational energy
levels for many of these states, but only the results relevant to the ground and
the (010) states are presented here. The experimental energies for these two
states have been fitted with the help of the bending-rotation Hamiltonian
approach [L. H. Coudert, J. Mol. Spectrosc. 181, 246-273 (1997)], and for each
rotational level, the calculated energy along with its uncertainty is reported
and compared with the observed value. Comparisons with other available energy
level data sets for the ground and (010) states are also presented. Copyright
1999 Academic Press.
PMID- 10191153
TI - Radiative Lifetimes for the C1Pi+/-u State of the H2 Molecule.
AB - Employing RKR electronic potentials for the C1Piu and X1Sigma+g states in
conjunction with Huffaker's correction and appropriate asymptotic functions, the
radiative lifetimes of rovibrational levels of the C1Piu state of H2 for v' = 0
13 and J' = 1, 5, 10, 15, 20, 25, and 28 are calculated. The perturbation between
C1Pi+u and B1Sigma+u has been considered and the perturbed lifetime was
calculated using unperturbed lifetimes. Copyright 1999 Academic Press.
PMID- 10191154
TI - HDO and D2O Low Pressure, Long Path Spectra in the 600-3100 cm-1 Region.
AB - High-resolution spectra of gas mixtures of HDO, D2O, and H2O were obtained with a
Fourier-transform spectrometer with path lengths up to 433 m. The spectra were
analyzed to obtain line positions and strengths of over 6000 transitions of HDO
and D2O. For HDO, these included the (000)-(000), (020)-(010), and (100)-(010)
bands of HD16O and the (010)-(000) bands of HD16O, HD17O, and HD18O. Several of
these assignments are reported for the first time. Of interest was the extended
coverage of the A-type transitions of the (010)-(000) band of HD16O. This is the
only A-type infrared band of any of the water vapor species (HDO, D2O, and H2O)
that is not involved in interactions with other bands. By this token, the A-type
dipole-moment expansion matrix elements can be tested without involving
perturbation theory. The measured linestrengths of the interacting bands, (020)
(010) and (100)-(010), were analyzed using a full perturbation treatment. Strong
localized Coriolis interactions affected only a few observed transitions.
Copyright 1999 Academic Press.
PMID- 10191155
TI - HDO and D2O Low Pressure, Long Path Spectra in the 600-3100 cm-1 Region.
AB - Measurements of line positions and absolute strengths of D2O from 700 to 3100 cm
1 were obtained with a Fourier transform spectrometer. The data were analyzed to
obtain energy levels of the (000), (010), (020), (100), and (001) vibrational
states of D216O and, first time assignments of the (010)-(000) band of D217O,
including the energy levels of the (000) and (010) states. The measurements
included transitions of the (010)-(000) band of D218O; however, observations from
a previous study provided adequate information for the energy levels. The
measured linestrengths of the (010)-(000) bands of D216O, D217O, and D218O were
fitted to the model, which included up to 19 dipole-moment expansion
coefficients. The observed linestrengths of the D216O interacting bands, (020)
(010), (100)-(010), and (001)-(010), were analyzed using a full perturbation
treatment. Copyright 1999 Academic Press.
PMID- 10191156
TI - Spectral Intensity and Lineshape Measurements in the First Overtone Band of HF
Using Tunable Diode Lasers.
AB - High-resolution absorption lineshapes for the P(3) and P(6) transitions of the
first overtone (v = 2-0) band of HF at 296 K have been measured using a pair of
distributed feedback diode lasers operating near 1.31 and 1.34 um, respectively.
Spectral line intensities and self-broadening parameters were determined by
fitting the measured spectra with Voigt, Galatry, and Rautian lineshape models.
Voigt profiles fit the low-pressure (<10 Torr) spectra of the P(3) transition
reasonably well due to the relatively strong collisional broadening effect.
Lineshape measurements of the P(6) transition (for pressures ranging from 5 to 60
Torr) show significant variation from the Voigt lineshape model due to velocity
changing collisions that effectively reduce the Doppler component of the spectral
line. Lineshape models that include motional (Dicke) narrowing effects, Galatry
(soft collision) and Rautian (hard collision) profiles yield significant
improvements in the spectral lineshape fits compared with Voigt profiles. The
collisional broadening coefficient (gamma) of the P(6) transition obtained from a
Voigt fit is approximately 4% lower than those found with either Galatry or
Rautian profile fits. The measured intensities and self-broadening coefficients
are compared with values in the HITRAN database and previous measurements.
Copyright 1999 Academic Press.
PMID- 10191157
TI - Algebraic Description of Anharmonic Stretching Vibrations.
AB - A U(2) algebraic model is presented to describe stretching vibrations of XYn (n =
2, 3, and 4) systems, where anharmonic interactions between the bond modes are
considered. This model in a limit corresponds to an anharmonically coupled local
mode model. As an example, the model for a molecule XY4 is applied to recently
observed spectra of methane in both gas and liquid phases, and the results
obtained are in good agreement with the experiments. Copyright 1999 Academic
Press.
PMID- 10191158
TI - Determination of a Potential Energy Surface for CO2 Using Generalized Internal
Vibrational Coordinates.
AB - A potential energy surface for CO2 is determined from experimental data using
generalized internal vibrational coordinates. These coordinates are defined as
two arbitrary distances and the angle between them and depend on two external
parameters, which can be properly optimized. An optimal generalized internal
coordinate system is obtained for CO2 by minimizing unconverged vibrational
energies with respect to the external parameters. The optimal coordinates are
shown to be superior to previously derived normal hyperspherical coordinates for
this molecule. A nonlinear least-squares fit of the potential energy surface of
CO2 to observed vibrational frequencies is made by using the optimal internal
coordinates and fully variational calculations. The potential function is
represented by a fourth-order Morse-cosine expansion and its quality is checked
by computing highly excited vibrational transition frequencies which were not
included in the fit. Copyright 1999 Academic Press.
PMID- 10191159
TI - The b1Sigma+(b0(+)) --> X3Sigma-(X10(+), X21) and a1Delta(a2) --> X21 Transitions
of SbF, SbCl, SbBr, and SbI.
AB - Emission spectra of the a1Delta(a2) --> X21 and b1Sigma+(b0(+)) --> X3Sigma
(X10(+), X21) transitions of SbF, SbCl, SbBr, and SbI have been observed in the
near-infrared spectral region. The antimony halide radicals were generated and
excited in a fast-flow system by reaction of antimony vapor (Sbx) with the
halides and microwave-discharged oxygen. The NIR chemiluminescence was measured
with a Fourier-transform spectrometer equipped with Ge and InSb detectors. The
spectra contain the known b1Sigma+(b0(+)) --> X3Sigma-(X10(+), X21) transitions
in the range 730-910 nm and the hitherto unknown a1Delta(a2) --> X21 transitions
in the range 1600-1900 nm. Vibrational analyses have yielded improved molecular
constants for the X10(+), X21, and b0(+) states and the following constants of
the a2 states (in cm-1): 121SbF: Te = 6815.6(5), omegae = 615.75(3), omegaexe =
2.62(1); 121Sb35Cl: Te = 6546.3(2), omegae = 379.8(1), omegaexe = 1.20(2);
121Sb79Br: Te = 6496.4(4), omegae = 265.9(2), omegaexe = 0.55(3); 121SbI: Te =
6366.7(3), omegae = 214.20(5), omegaexe = 0.430(9), where the numbers in
parentheses are the standard deviations of the parameters. Copyright 1999
Academic Press.
PMID- 10191160
TI - Absolute Line Intensities for the nu6 Band of H2O2.
AB - The purpose of this work was to obtain reliable absolute intensities for the nu6
band of H2O2. It was undertaken because strong discrepancies exist between the
different nu6 band intensities which are presently available in the literature
(A. Perrin, A. Valentin, J.-M. Flaud, C. Camy-Peyret, L. Schriver, A. Schriver,
and P. Arcas, J. Mol. Spectrosc. 1995. 171, 358), (R. May, J. Quant. Radiat.
Transfer 1991. 45, 267), and (R. L. Sams, personal communication). The method
which was chosen in the present work was to measure simultaneously the far
infrared absorptions and the nu6 absorptions of H2O2. Consequently, Fourier
transform spectra of H2O2 were recorded at Giessen in a spectral range (370-1270
cm-1) which covers both the R branch of the torsion-rotation band and the P
branch of the nu6 band which appear at low and high wavenumbers, respectively.
From the low wavenumber data, the partial pressure of H2O2 present in the cell
during the recording of the spectra was determined by calibrating the observed
absorptions in the torsion-rotation band with intensities computed using the
permanent H2O2 dipole moment measured by Stark effect (A. Perrin, J.-M. Flaud, C.
Camy-Peyret, R. Schermaul, M. Winnewisser, J.-Y. Mandin, V. Dana, M. Badaoui, and
J. Koput, J. Mol. Spectrosc. 1996. 176, 287-296) and [E. A. Cohen and H. M.
Pickett, J. Mol. Spectrosc. 1981. 87, 582-583). In the high frequency range, this
value of the partial pressure of H2O2 was used to measure absolute line
intensities in the nu6 band. Finally, the line intensities in the nu6 band were
fitted using the theoretical methods described in detail in our previous works.
Using these new results on line intensities together with the line position
parameters that we obtained previously, a new synthetic spectra of the nu6 band
was generated, leading to a total band intensity of 0.185 x 10(-16) cm
1/(molecule.cm-2) at 296 K. It has to be pointed out that the new line
intensities agree to within the experimental uncertainties with the individual
line intensity measurements performed previously by May and by Sams. Copyright
1999 Academic Press.
PMID- 10191161
TI - The A (3Pi1) State of ClF.
AB - The A(3Pi1) state of ClF is studied (1) in emission from the beta(1(3)P2) ion
pair state in a high-pressure discharge, (2) from its role in perturbations of
the B(3Pi0(+)) and A'(3Pi2) states, and (3) in direct absorption from the
X(1Sigma+) ground state. The last of these is obtained via a UV-labeling
technique and represents the first observation of the A <-- X transition. The
emission spectrum yields extensive assignments for the 0-4, 0-5, and 1-4 bands of
beta --> A, with both e and f lines identified. The well-known perturbation in v
= 7 of the B state is attributed to interaction with v = 9 of A. A newly
identified perturbation in B(6) involves coupling with A(8). The known
perturbation in B(8) may involve A(11), but other assignments cannot be ruled
out. Approximate potential curves are derived for all three valence states and
used to compute the vibrational factors for the perturbations, permitting
extraction of the electronic coupling strengths. The B-A coupling elements are
within approximately 10% of expectations for rotation-electronic coupling within
a Hund's case (a) 3Pi manifold, but the strength of the perturbation between A(5)
and A'(6) is only about 30% of predictions for this model. Copyright 1999
Academic Press.
PMID- 10191162
TI - Rotational Spectra of Conformers and Isotopomers of 1-Hydroxynaphthalene.
AB - The rotational spectra of cis- and trans-1-hydroxynaphthalene and trans-1-DO
naphthalene have been recorded between 6 and 18 GHz using a pulsed microwave
spectrometer. Most of the transitions detected are a type; hyperfine splittings
from the electric quadrupole interaction were observed for some transitions of
the deuterated isotopomer. The frequencies were well modeled with an S-reduced
asymmetric rotor Hamiltonian. The rotational constants were determined much more
accurately than previously. In addition, the quartic centrifugal distortion
parameters were determined for the first time. Their values were very small,
consistent with the rigid framework of this aromatic molecule. Theoretical
calculations were carried out to support the assignment of the two forms to the
cis and trans conformers. These calculations suggested that the cis conformer is
slightly nonplanar in its equilibrium configuration, a property which is not
inconsistent with its rotational constants. Copyright 1999 Academic Press.
PMID- 10191163
TI - Terahertz Spectroscopy of the Amidogen Radical, NH2.
AB - The rotational spectrum of the NH2 radical in its &Xtilde;2B1 ground vibronic
state was investigated between 614 and 1003 GHz. One hundred fifty-nine newly
observed lines (188 hyperfine components) of six rotational transitions with 0
= N = 5 and 0 = Ka = 4 were used in the final, global fit of field-free
data for the (000) vibrational state. Recent results from Fourier transform far
infrared (FT-FIR), and millimeter- and submillimeter-wave spectroscopy, as well
as microwave optical double resonance (MODR) and recent FIR laser sideband data,
were also used in the fit. A large set of spectroscopic constants reproduces the
input data within experimental uncertainties and permits the precise prediction
of low-N, low-Ka transitions of interest for the astrophysical community. In
particular, the astrophysically important 111-000 transition of ortho NH2 was
observed near 952.57 and 959.50 GHz. Copyright 1999 Academic Press.
PMID- 10191164
TI - FTIR Emission Spectra and Molecular Constants for DCl.
PMID- 10191165
TI - The effect of slice order and thickness on fMRI activation data using multislice
echo-planar imaging.
AB - Multislice echo-planar imaging (EPI) is a commonly used technique for fMRI
studies. Brain activation images acquired using fMRI are sensitive to T2*
changes, reflecting the level of blood oxygenation (BOLD contrast), and may also
contain an element of T1 contrast which detects blood flow changes in large
vessels. If slice inflow (T1) effects are significant in multislice EPI, then as
the order in which the slices are acquired is changed, differences in the
activation maps are predicted. However, in experiments presented here using
visual stimulation, the data demonstrate that highly consistent results can be
achieved for repetition times (TR) of 6.0, 3.0, and 1.5 s. This suggests that,
for whole-brain multislice EPI, fMRI activation is dominated by T2*, BOLD
contrast. The thickness of the imaging slice is also an important parameter in
these studies, having implications for spatial resolution, sensitivity, and
acquisition time. In separate visual cortex experiments the effect on the values
of the fMRI Z scores and the number of activated voxels is investigated as a
function of slice thickness (from 1 to 8 mm). The maximum Z scores in the data
are similar for all slice thicknesses and, after resampling to allow a direct
comparison to be made, the volume of visual cortex detected as significantly
activated increases with slice thickness.
PMID- 10191166
TI - Impaired effective cortical connectivity in vegetative state: preliminary
investigation using PET.
AB - Vegetative state (VS) is a condition of abolished awareness with persistence of
arousal. Awareness is part of consciousness, which itself is thought to represent
an emergent property of cerebral neural networks. Our hypothesis was that part of
the neural correlate underlying VS is an altered connectivity, especially between
the associative cortices. We assessed regional cerebral glucose metabolism
(rCMRGlu) and effective cortical connectivity in four patients in VS by means of
statistical parametric mapping and [18F]fluorodeoxyglucose-positron emission
tomography. Our data showed a common pattern of impaired rCMRGlu in the
prefrontal, premotor, and parietotemporal association areas and posterior
cingulate cortex/precuneus in VS. In a next step, we demonstrated that in VS
patients various prefrontal and premotor areas have in common that they are less
tightly connected with the posterior cingulate cortex than in normal controls.
These results provide a strong argument for an alteration of cortical
connectivity in VS patients.
PMID- 10191167
TI - High-resolution mapping of discrete representational areas in rat somatosensory
cortex using blood volume-dependent functional MRI.
AB - The present study documents the use of an iron oxide-based blood-pool contrast
agent in functional magnetic resonance imaging to monitor activity-related
changes in cerebral blood volume (CBV) resulting from peripheral sensory
stimulation and the application of this technique to generate high-resolution
functional maps. Rats, anesthetized with alpha-chloralose, were imaged during
electrical stimulation (3 ms, 3 Hz, 3 V) of forelimb or hindlimb. Activation maps
were generated by cross-correlation of the measured signal response and a square
wave function representative of the stimulus for each image pixel. Multislice
imaging produced functional maps consistent with the known functional anatomy of
rat primary somatosensory (S-I) cortex. Imaging with improved temporal resolution
demonstrated rapid (<6 s) CBV increases which were sustained and relatively
stable (coefficient of variation = 0.17 +/- 0.02) for forelimb stimulation
periods of up to 5 min. Enabled by this sustained response we generated high
resolution (approximately 100 micrometer in-plane) functional maps showing
discrete forelimb and hindlimb activation. This technique offers many advantages
over other methods for the study of brain activity in the rat and has resolution
sufficient to be useful in reorganization studies.
PMID- 10191168
TI - Measuring in vivo myelination of human white matter fiber tracts with
magnetization transfer MR.
AB - Precise characterization of white matter pathways is important for the
understanding of structural-functional relationships in the human brain. While it
is known from postmortem studies that the connectivity of cortical areas is
conveyed by projection, commissural, and association fibers, most clinical
studies disregard useful information about specific fiber tracts. Magnetization
transfer (MT) MR detects the relative proportion of free mobile protons and
immobile protons bound to macromolecules. MT values correlate with histopathology
and it has been proposed that in the white matter, the amount of magnetization
transfer correlates with the degree of myelination. Thus, MT-MR provides measures
that may reflect more accurately the physiology and natural course of diseases
involving the white matter. We applied this quantitative in vivo method to five
children at different ages to determine whether the maturational changes of
distinct fiber tracts could be measured. All regions of interest were localized
by means of Brodmann's original descriptions and the additional use of
reconstructed 3D-matched data from 10 myelin-stained human brain specimens. With
this atlas-guided approach we localized and measured 26 supratentorial white
matter fiber tracts in each hemisphere, connecting to primary as well as
association cortices. All fiber tracts showed consistent age-related MT changes
and the strongest effects were found in those tracts projecting to the primary
cortical areas. These results suggest that our method is suitable for in vivo MT
measurements in specific fiber tracts. It can provide data that relate to
myelination during ontogenesis or myelination delays in myelin disorders. In the
clinical domain, the focus on specific fiber tracts appears to be advantageous
over standard approaches, because such system of parcellation is based on the
functional anatomy of the white matter. Consequently, it may be especially useful
for topical analysis in neurology allowing the assessment of the functional
consequences of white matter damage as well as the effectiveness of treatments in
patients with any lesion that can be visualized by MRI.
PMID- 10191169
TI - Localization of cardiac-induced signal change in fMRI.
AB - Signal detection in the analysis of blood oxygen level-dependent (BOLD)
functional magnetic resonance imaging (fMRI) may be greatly hindered by cardiac
pulsatility artifacts. Vessel pulsation, cerebrospinal fluid movement, and tissue
deformation are all associated with the cardiac cycle and all can produce fMRI
signal variance. Most cognitive fMRI studies do not utilize a method of cardiac
related noise reduction, in part because of the lack of information on the
regional significance and magnitude of cardiac-related signal variance in the
brain. In this paper we present a topographical description of the regions
showing significant contributions of cardiac-related signal variance. The results
are highly consistent across subjects and suggest that reduced sensitivity due to
cardiac-induced noise in the BOLD signal is systematically greater in specific
areas, typically near major blood vessels. Significant effects of cardiac-related
variability were found on average in 27.5 +/- 8.0% of voxels. Strong influences
were found along the vertebrobasilar arterial system near the medial areas of the
brain, along the middle cerebral artery near the anterior temporal lobes and in
the insula, and along the anterior cerebral artery in the anterior
interhemispheric fissure in the medial frontal lobes. Significant effects were
also observed in the sigmoid transverse and superior sagittal sinus regions.
These results identify regions in which fMRI will have reduced sensitivity due to
increased signal variation produced by cardiac pulsatility.
PMID- 10191170
TI - Deconvolution of impulse response in event-related BOLD fMRI.
AB - The temporal characteristics of the BOLD response in sensorimotor and auditory
cortices were measured in subjects performing finger tapping while listening to
metronome pacing tones. A repeated trial paradigm was used with stimulus
durations of 167 ms to 16 s and intertrial times of 30 s. Both cortical systems
were found to be nonlinear in that the response to a long stimulus could not be
predicted by convolving the 1-s response with a rectangular function. In the
short-time regime, the amplitude of the response varied only slowly with stimulus
duration. It was found that this character was predicted with a modification to
Buxton's balloon model. Wiener deconvolution was used to deblur the response to
concatenated short episodes of finger tapping at different temporal separations
and at rates from 1 to 4 Hz. While the measured response curves were distorted by
overlap between the individual episodes, the deconvolved response at each rate
was found to agree well with separate scans at each of the individual rates.
Thus, although the impulse response cannot predict the response to fully
overlapping stimuli, linear deconvolution is effective when the stimuli are
separated by at least 4 s. The deconvolution filter must be measured for each
subject using a short-stimulus paradigm. It is concluded that deconvolution may
be effective in diminishing the hemodynamically imposed temporal blurring and may
have potential applications in quantitating responses in eventrelated fMRI.
PMID- 10191171
TI - A direct comparison between whole-brain PET and BOLD fMRI measurements of single
subject activation response.
AB - We present the results of a direct comparison of single-subject activation using
identical tasks for both functional PET and fMRI whole-brain studies. We examined
the most commonly employed methods for each modality. For fMRI this is the blood
oxygenation level-dependent (BOLD) contrast method with echo-planar imaging. In
PET single-subject activation studies are based on the development of high
sensitivity 3D imaging of regional cerebral blood flow from multiple [15O]water
injections. The identical activation paradigm of a visually cued sequential
finger opposition was used for PET and fMRI. For both modalities the entire brain
volume difference images were smoothed to the same final resolution and the peak
t value within the primary sensory/motor (PSM) area was then identified. All
contiguous voxels in the PSM above a predetermined threshold of statistical
significance were determined. Finally, the difference-weighted centroid location
was calculated for the PSM region for each modality. These studies showed a very
similar pattern of activation, with the volume of activation greater in fMRI and
higher levels of statistical significance. The centroids of activation, however,
differed by 9 +/- 3 mm between the modalities, with the fMRI centroid location
dorsal to that for PET. These results were stable across all processing options
including differing levels of image smoothing and thresholds of statistical
significance. These results are consistent with the hypothesis that draining
veins contribute a substantial signal for fMRI activation studies and indicate
caution for the interpretation of BOLD fMRI images with activation sites near
draining veins.
PMID- 10191172
TI - Optimal staining methods for delineation of cortical areas and neuron counts in
human brains.
AB - For cytoarchitectonic delineation of cortical areas in human brain, the Gallyas
staining for somata with its sharp contrast between cell bodies and neuropil is
preferable to the classical Nissl staining, the more so when an image analysis
system is used. This Gallyas staining, however, does not appear to be appropriate
for counting neuron numbers in pertinent brain areas, due to the lack of distinct
cytological features between small neurons and glial cells. For cell counting
Nissl is preferable. In an optimal design for cell counting at least both the
Gallyas and the Nissl staining must be applied, the former staining for
cytoarchitectural delineaton of cortical areas and the latter for counting the
number of neurons in the pertinent cortical areas.
PMID- 10191173
TI - Comparison of 3D BOLD functional MRI with spiral acquisition at 1.5 and 4.0 T.
AB - In order to investigate the merit of high field strength for BOLD-contrast-based
functional magnetic resonance imaging (fMRI) studies, multishot gradient-echo
fMRI experiments during motor cortex activation were performed on 1.5- and 4.0-T
scanners with equivalent hardware, on the same volunteers. In these studies,
artifactual vascular enhancement related to inflow effects was minimized, and
large brain areas were covered by using a 3D scan technique. Temporal signal
stability was optimized by using spiral readout gradients. The sensitivity for
detection of activated regions was assessed by measuring the number of "activated
voxels" and their average t score in predefined regions of interest. When
comparing fMRI experiments with the same total scan time, performed on six
subjects, and with acquisition parameters optimized for each field strength
separately, the 4.0-T scanner proved to give superior results, with a 70% greater
number of activated voxels and a 20% higher average t score for the activated
voxels.
PMID- 10191174
TI - Introduction.
PMID- 10191175
TI - Estimation of mutation frequencies in normal mammalian cells and the development
of cancer.
AB - A current controversy in cancer research is whether the rate of accumulation of
mutations in normal somatic cells is sufficient to account for the number of
mutations in malignant cells. This review will focus on the types of mutations
that can occur in mammalian somatic cells and the frequency at which some of
these mutations have been shown to occur in vivo. Human and mouse mutation
detection systems will be highlighted. The possibility that distinct mutational
events can arise from a common precursor will be discussed, as will the
possibility that inherited and sporadic cancers can acquire mutator phenotypes at
different times in tumor development. Consideration will also be given to a
potential relationship between an age-related accumulation of mutations and
cancer.
PMID- 10191176
TI - On the origin of multiple mutations in human cancers.
AB - Tumor progression is a multi-step process, proceeding by multiple alterations
from a normal cell to a localized tumor, and finally to one that acquires the
ability to invade and metastasize. Tumors are characterized by many mutations in
the form of base substitutions, deletions, chromosomal translocations, and gene
amplifications, and these mutations are found to accumulate as tumors progress.
In contrast, spontaneous mutations are very rare events. Considering the high
fidelity of DNA replication in normal cells, it seems improbable that spontaneous
mutations could be the source of the large numbers of genetic alterations that
are observable in cancer cells. The question of how multiple mutations accumulate
in tumor cells is one of considerable interest, since understanding the source of
these mutations may facilitate the detection of tumors and may provide new
approaches to cancer prevention. We have proposed that the multiple mutations
detectable in cancer cells result from a mutator phenotype, in which loss of a
genome stability function occurs early during tumor development and predisposes
the tumor cell to the accumulation of further mutations. We will first consider
the evidence that cancer cells manifest a mutator phenotype, and subsequently
discuss the possibility that a mutator phenotype can be selected and can be
transient as tumors progress.
PMID- 10191177
TI - Hypermutability and silent mutations in human carcinogenesis.
AB - Silent or synonymous mutations are nucleotide changes which do not result in an
amino acid change. Such alterations make up approximately 4% of the total TP53
mutations in a database of almost 10,000 mutations. Insofar as these changes do
not confer a selective advantage, silent mutations make it possible to estimate
an unbiased mutation frequency. Since this frequency is at least 100 times higher
than would be expected for normal tissue, tumors must be hypermutable. In
addition, a class of tumors may be supermutable with a mutation frequency
comparable to that observed in the generation of immune diversity.
PMID- 10191178
TI - Evolution and the inevitability of human cancer.
AB - Natural selection, which is absolutely dependent on genetic differences between
individuals, is the process by which life has evolved on this planet. Genetic
variability is ultimately depended on the occurrence of new mutations in the germ
line of species. The rate at which this occurs appears not to be arbitrary or
dependent on chance external events. Rather the available evidence suggests that
it is highly controlled and determined by endogenous processes. However, the body
does not have separate mechanisms for controlling mutation frequency in the
germinal and somatic lineages and the selective process described inevitably has
also led to somatic cells being subject to mutation accumulation. Indeed, since
mutation frequency increases exponentially with time, the human somatic mutation
frequency at approximately 80 years of age in epithelial tissues appears to be
more than 10-fold higher than in the human germline. This normal but highly
elevated somatic mutation frequency is sufficient to account for the complex
multi-step process of human tumorigenesis even in the absence of the effects of
major external mutagens or rare transitions to even more elevated mutation
frequencies. Thus, scrutiny of the apparently disparate biological phenomena of
evolution and tumorigenesis leads to the postulate that they are in fact two
interdependent manifestations of the same underlying process and that given an
evolutionary process dependent on mutation accumulation then cancer in long lived
organisms is an inevitable consequence.
PMID- 10191180
TI - Volume and contents of volume 8, 1998
PMID- 10191179
TI - The use of genetic instability as a clinical tool for cancer diagnosis.
AB - Human tumors exhibit two fundamentally important characteristics, extensive
genetic alteration and clonality. Although it is still unclear to what extent
tumors have an elevated mutational burden as compared with normal tissue, their
clonality results in their ready detection. Thus, assaying tissues for clonal
alterations at frequently mutated microsatellite loci represents a viable
approach to cancer diagnosis. The most remarkable extension of this concept is
that not only can cancer cells be detected in biological samples, but tumor DNA
can also be directly detected in the serum or plasma of patients with some forms
of cancer. This recent finding is currently being explored but may represent an
important contribution to future diagnostic strategies.
PMID- 10191181
TI - The gamma2 late glycoprotein K promoter of equine herpesvirus 1 is differentially
regulated by the IE and EICP0 proteins.
AB - The equine herpesvirus 1 immediate-early (IE) phosphoprotein is essential for the
activation of transcription from viral early and late promoters and trans
represses its own promoter. Transient-transfection assays showed that the IE
protein trans-represses the gamma2 late gK promoter. Gel shift and DNase I
footprinting assays demonstrated that the IE protein binds to the gK promoter
sequences from -42 to -26 and from -13 to +12 that overlap the transcription
initiation site (+1). These results indicated that the IE protein binds to the
transcription initiation site of the gK promoter sequences, thereby repressing
transcription. On the other hand, the EICP0 protein trans-activates the gamma2
late gK promoter [Bowles, D. E., Holden, V. R., Zhao, Y., and O'Callaghan, D. J.
(1997). The ICP0 protein of equine herpesvirus 1 is an early protein that
independently transactivates expression of all classes of viral promoters. J.
Virol. 71, 4904-4914]. Overall, the EICP0 protein is able to release the gK
promoter from the repressive effects of the IE protein. It has not been
previously demonstrated that the major immediate-early transcriptional regulator
of a herpesvirus represses expression of a late gene during infection.
PMID- 10191182
TI - Human immunodeficiency virus type 1 genetic evolution in patients with prolonged
suppression of plasma viremia.
AB - Treatment of human immunodeficiency virus type 1 (HIV-1)-infected patients with
combination drug regimens results in a reduction of plasma viral load to levels
below the limit of detection. To investigate the genomic fluctuations in HIV-1
populations from long-term responders to antiviral therapies we analyzed the
viral sequence evolution of env and pol genes from sequential peripheral blood
mononuclear cell (PBMC) DNA samples of three infected patients. Analyses of
sequences covering the V3 and flanking env regions obtained from blood samples at
the beginning of the therapy and at 14 or 24 months from baseline revealed that
HIV-1 quasispecies continue to evolve in the three patients following combination
antiretroviral therapy. Minor drug-resistant mutant subpopulations were also
searched for and found in one patient. Interestingly, no minor resistant
subpopulations were found in the other two patients despite the fact that they
showed evidence of ongoing viral replication. Finally, the genetic analysis of
the env gene shows a reduction in PBMC env viral population diversity after long
term response to the therapy in all the patients analyzed.
PMID- 10191183
TI - Salmon pancreas disease virus, an alphavirus infecting farmed Atlantic salmon,
Salmo salar L.
AB - A 5.2-kb region at the 3' terminus of the salmon pancreas disease virus (SPDV)
RNA genome has been cloned and sequenced. The nucleotide and predicted amino acid
sequences show that SPDV shares considerable organizational and sequence identity
to members of the genus alphavirus within the family Togaviridae. The SPDV
structural proteins encoded by the 5.2-kb region contain a number of unique
features when compared to other sequenced alphaviruses. Based on cleavage site
homologies, the predicted sizes of the SPDV envelope glycoproteins E2 (438 aa)
and E1 (461 aa) are larger than those of other alphaviruses, while the predicted
size of the alphavirus 6K protein is 3.2 K (32 aa) in SPDV. The E2 and E1
proteins each carry one putative N-linked glycosylation site, with the site in E1
being found at a unique position. From amino acid sequence comparisons of the
SPDV structural region with sequenced alphaviruses overall homology is uniform,
ranging from 32 to 33%. While nucleotide sequence analysis of the 26S RNA
junction region shows that SPDV is similar to other alphaviruses, analysis of the
3'-nontranslated region reveals that SPDV shows divergence in this region.
PMID- 10191184
TI - Detection of Epstein-Barr virus (EBV) in hepatocellular carcinoma tissue: a novel
EBV latency characterized by the absence of EBV-encoded small RNA expression.
AB - In this study, we investigated the presence of Epstein-Barr virus (EBV) in liver
tissue from 35 patients with hepatocellular carcinoma (HCC). EBV DNA was detected
in 13 patients (37%) by Southern blot hybridization. In 10 of these patients, EBV
DNA was present in tumor tissue only, whereas in the other 3, it was detected in
both tumor and nontumor tissues. The quantity of EBV DNA detected was equivalent
to 1-10 viral DNA molecules/100 cells. EBV-determined nuclear antigen was
detected in 7-13% of the carcinoma cells in three tumor tissue samples that
contained approximately one copy of the EBV genome/10 cells. A single terminal
fragment of EBV DNA was identified in these tissues, suggesting that the EBV
infected cells in HCC represent clonal proliferation. Western blotting and
reverse transcription-polymerase chain reaction analyses demonstrated that these
three tumor tissue specimens were positive for EBV-determined nuclear antigen 1
and BamHI A transcripts but were negative for the other latent EBV products,
including EBV-encoded small RNA. The results indicated that there is a high EBV
load in HCC tissue and that all of the HCC tissue examined showed a novel pattern
of EBV latency characterized by absence of EBV-encoded small RNA expression.
PMID- 10191186
TI - Infectious laryngotracheitis virus, an alpha herpesvirus that does not interact
with cell surface heparan sulfate.
AB - Among the alpha herpesviruses studied to date, the initial stage of wild-type
virus attachment involves an interaction between virally encoded structural
envelope glycoproteins (predominantly glycoprotein C) and cell surface heparan
sulfate proteoglycans. An analysis of the infectious laryngotracheitis virus
(ILTV) glycoprotein C and glycoprotein B sequences suggested that these proteins
lacked consensus heparin-binding domains. This indicated that ILTV might attach
to its host cell in a heparan-independent manner, distinct from other alpha
herpesviruses. The infectivity of two ILTV strains, a tissue-culture-adapted
vaccine strain and a virulent field challenge strain, were found to be
insensitive to the presence of exogenous heparin or chondroitin. Furthermore,
infectivity was retained in chicken embryonic liver cells treated with
heparinase. However, 4 degrees C attachment studies and penetration studies in
the presence of citrate buffer clearly demonstrated that ILTV attaches stably to
and effectively penetrates chicken embryonic liver cells. Consequently, ILTV
represents an alpha herpesvirus whose initial attachment step does not involve
interactions with heparan or chondroitin sulfate containing proteoglycans.
PMID- 10191185
TI - Role of nitric oxide in pathogenesis of herpes simplex virus encephalitis in
rats.
AB - The role of nitric oxide (NO) in the pathogenesis of viral encephalitis was
investigated by using an experimental model of herpes simplex virus type 1 (HSV
1) encephalitis in Lewis rats. The expression of inducible NO synthase (iNOS)
mRNA determined by Northern blotting was observed first in the olfactory bulb and
the brain stem on day 5 after intranasal inoculation of HSV-1, and thereafter
iNOS mRNA was detected in other brain regions, i.e., cerebrum and cerebellum. In
various parts of the brain, excessive NO production was identified by electron
spin resonance spectroscopy. The temporal and spatial patterns of iNOS expression
coincided with those of viral propagation, as demonstrated by polymerase chain
reaction for HSV-1 gene expression as well as by the plaque-forming assay.
Immunohistochemical study determined that iNOS was localized mainly in monocyte
derived macrophages. Treatment of virus-infected animals with the NOS inhibitor
Nomega-monomethyl-l-arginine (l-NMMA), but not Nomega-monomethyl-d-arginine,
significantly ameliorated not only clinical symptoms such as paralysis and
seizures but also mortality. Virus yield from brain tissue was not affected by l
NMMA treatment. It is of interest that increased expression of the antioxidant
enzyme heme oxygenase-1 was observed in the HSV-1-infected brain; this increased
expression was strongly inhibited by l-NMMA treatment. These data suggest that
the high level of NO produced by iNOS is a pathogenic factor in HSV-1-induced
encephalitis in rats.
PMID- 10191187
TI - Herpes simplex virus entry is associated with tyrosine phosphorylation of
cellular proteins.
AB - The initial step in herpes simplex virus (HSV) entry is binding of virion
glycoprotein (g)C and/or gB to cell surface heparan sulfate. After this initial
attachment, gD interacts with cell surface receptor or receptors, and the virion
envelope fuses with the cell membrane. Fusion requires viral glycoproteins gB,
gD, gL, and gH, but the cellular factors that participate in or the pathways
activated by viral entry have not been defined. To determine whether signal
transduction pathways are triggered by viral-cell fusion, we examined the
association of viral entry with tyrosine phosphorylation of cellular proteins.
Using immunoprecipitation and Western blotting, we found that at least three
cytoplasmic host cell proteins, designated p80, p104, and p140, become tyrosine
phosphorylated within 5-10 min after exposure to HSV-1 or HSV-2. However, no
phosphorylation is detected when cells are exposed to a mutant virus deleted in
gL that binds but fails to penetrate. Phosphorylation is restored when the gL
deletion virus is grown on a complementing cell line. Viral entry and the
phosphorylation of p80, p104, and p140 are inhibited when cells are infected with
virus in the presence of protein tyrosine kinase inhibitors. Taken together,
these studies suggest that tyrosine phosphorylation of host cellular proteins is
triggered by viral entry.
PMID- 10191188
TI - Transcription of the genome of the filamentous bacteriophage cf from both plus
and minus DNA strands.
AB - The filamentous bacteriophage cf infects the bacterium Xanthomonas campestris pv.
citri. Northern blot analysis with probes derived from various restriction
fragments of cf replicative form (RF) DNA has revealed the presence of five major
phage-specific transcripts in infected cells. Four of these transcripts were
shown to be derived from the region of the cf genome extending from gene II to
gene VIII and are consistent with the cascade model of transcription proposed for
Ff coliphages. These transcripts overlap with each other and terminate upstream
of an efficient Rho-independent transcription terminator. Unlike the well
characterized Ff phages, in which only the minus strand of viral DNA serves as a
transcription template, both strands of the RF DNA of phage cf appeared to be
transcribed. Thus one of the five major cf transcripts was shown to be derived
from a region of the viral minus strand that contains an open reading frame
encoding a putative polypeptide of 165 amino acids. Primer extension analysis
mapped the transcriptional initiation site of this RNA to a cytosine residue at
position 870. A partial transcription map of phage cf revealed two independent
regions of transcriptional activity. The region with the highest activity
coincides with that encoding the polypeptides required in the largest amounts
during the cf infection cycle.
PMID- 10191189
TI - Role of the myxoma virus soluble CC-chemokine inhibitor glycoprotein, M-T1,
during myxoma virus pathogenesis.
AB - Myxoma virus is a poxvirus that causes a virulent systemic disease called
myxomatosis in European rabbits. Like many poxviruses, myxoma virus encodes a
variety of secreted proteins that subvert the antiviral activities of host
cytokines. It was recently demonstrated that the myxoma virus M-T1 glycoprotein
is a member of a large poxvirus family of secreted proteins that bind CC
chemokines and inhibit their chemoattractant activities in vitro. To determine
the biological role of M-T1 in contributing to myxoma virus virulence, we
constructed a recombinant M-T1-deletion mutant virus that was defective in M-T1
expression. Here, we demonstrate that M-T1 is expressed continuously during the
course of myxoma virus infection as a highly stable 43-kDa glycoprotein and is
dispensable for virus replication in vitro. Deletion of M-T1 had no significant
effects on disease progression or in the overall mortality rate of infected
European rabbits but heightened the localized cellular inflammation in primary
tissue sites during the initial 2 to 3 days of infection. In the absence of M-T1
expression, deep dermal tissues surrounding the primary site of virus inoculation
showed a dramatic increase in infiltrating leukocytes, particularly
monocytes/macrophages, but these phagocytes remained relatively ineffective at
clearing virus infection, likely due to the concerted properties of other
secreted myxoma virus proteins. We conclude that M-T1 inhibits the chemotactic
signals required for the influx of monocytes/macrophages during the acute-phase
response of myxoma virus infection in vivo, as predicted by its ability to bind
and inhibit CC-chemokines in vitro.
PMID- 10191190
TI - Use of a high-affinity peptide that aborts MHC-restricted cytotoxic T lymphocyte
activity against multiple viruses in vitro and virus-induced immunopathologic
disease in vivo.
AB - Binding of a specific peptide(s) from a viral protein to major histocompatibility
complex (MHC) class I molecules is a critical step in the activation of CD8(+)
cytotoxic T lymphocytes (CTLs). Once activated, CTLs can cause lethal disease in
an infected host, for example, by killing virus-containing ependymal and
ventricular cells in the central nervous system or viral protein-expressing beta
cells in the pancreatic islets of Langerhans. Here we describe the usage of a
designed (not natural) high-affinity peptide to compete with viral peptide(s)-MHC
binding. This peptide blocks virus-induced CTL-mediated disease both in the CNS
and in the pancreatic islets in vivo. Further, the blocking peptide aborts MHC
restricted killing of target cells by CTLs generated to three separate viruses:
lymphocytic choriomeningitis virus, influenza virus, and simian virus 40.
PMID- 10191191
TI - Immunogenicity of herpes simplex virus type 1 mutants containing deletions in one
or more alpha-genes: ICP4, ICP27, ICP22, and ICP0.
AB - Replication defective mutants of HSV have been proposed both as vaccine
candidates and as vehicles for gene therapy because of their inability to produce
infectious progeny. The immunogenicity of these HSV replication mutants, at both
qualitative and quantitative levels, will directly determine their effectiveness
for either of these applications. We have previously reported (Brehm et al., J.
Virol., 71, 3534, 1997) that a replication defective mutant of HSV-1, which
expresses a substantial level of viral genes without producing virus particles,
is as efficient as wild-type HSV-1 in eliciting an HSV-specific cytotoxic T
lymphocyte (CTL) response. In this report, we have further evaluated the
immunogenic potential of HSV-1-derived replication defective mutants by examining
the generation of HSV-specific CTL following immunization with viruses that are
severely restricted in viral gene expression due to mutations in one or more HSV
alpha genes (ICP4, ICP27, ICP22, and ICP0). To measure the CTL responses induced
by the HSV alpha-mutants, we have targeted two H-2Kb-restricted CTL epitopes: an
epitope in a virion protein, gB (498-505), and an epitope in a nonvirion protein,
ribonucleotide reductase (RR1 822-829). The HSV mutants used in this study are
impaired in their ability to express gB while a majority of them still express
RR1. Our findings demonstrate that a single immunization with these mutants is
able to generate a strong CTL response not only to RR1 822-829, but also to gB498
505 despite their inability to express wild-type levels of gB. Furthermore, a
single immunization with any individual mutant can also provide immune protection
against HSV challenge. These results suggest that mutants which are restricted in
gene expression may be used as effective immunogens in vivo.
PMID- 10191192
TI - Bean yellow dwarf virus RepA, but not rep, binds to maize retinoblastoma protein,
and the virus tolerates mutations in the consensus binding motif.
AB - It has previously been reported that complementary-sense gene products of wheat
dwarf virus (WDV), a geminivirus of the genus Mastrevirus that infects
monocotyledonous plants, bind to human and maize retinoblastoma (Rb) protein. Rb
proteins control cell-cycle progression by sequestering transcription factors
required for entry into S-phase, suggesting that the virus modifies the cellular
environment to produce conditions suitable for viral DNA replication. Using a
yeast two-hybrid assay, we have investigated whether the complementary-sense gene
products of bean yellow dwarf virus, a mastrevirus that is adapted to
dicotyledonous plants, also bind maize Rb protein. We demonstrate that whereas
RepA binds to Rb protein, Rep does not, suggesting that RepA alone regulates host
gene expression and progression of cells to S-phase. RepA mutants containing L -
> I, C --> S, C --> G, and E --> Q mutations within the consensus Rb protein
binding motif LXCXE retained the ability to bind to Rb, but with reduced
efficiency. Most notably, the E --> Q mutation reduced binding by approximately
95%. Nonetheless, all LXCXE mutants were able to replicate in tobacco protoplasts
and to systemically infect Nicotiana benthamiana and bean, in which they produced
wild-type symptoms.
PMID- 10191193
TI - Identification of the canarypox virus thymidine kinase gene and insertion of
foreign genes.
AB - We mapped the canarypox virus (CaPV) thymidine kinase (TK) gene within a 5.8-kbp
XbaI fragment of the genome by Southern blotting using the fowlpox virus (FPV) TK
gene as a probe. Nucleotide sequence analysis of the fragment revealed seven open
reading frames (ORFs) showing gene organization similar to that of FPV. The TK
gene contained in this region had an ORF of 179 amino acids encoding a
polypeptide with a putative molecular mass of 20.0 kDa. An A/T-rich region and a
transcription termination signal, TTTTTAT, were found upstream and at the end of
the ORF, which is consistent with poxvirus early gene regulation. The consensus
sequence of the late promoter TAAAT also overlapped with the initiation codon of
the ORF. The amino acid sequence similarity between the TK genes of CaPV and FPV,
avipoxviruses, was 64.2%, which was lower than the similarities between vaccinia
and variola orthopoxviruses (97.2%) and between Shope fibroma and myxoma
leporipoxviruses (82.6%). However, the monophyly of avian clades of CaPV and FPV
was supported by phylogenetic analysis. We then inserted the genes encoding lacZ,
luciferase (luci), and envelope of human T-lymphotropic virus type 1 (HTLV-1 env)
into the TK gene of CaPV to evaluate its suitability as an expression vector. The
recombinant viruses obtained were unstable, although the foreign genes were
expressed efficiently in the mammalian cells infected with the viruses.
PMID- 10191194
TI - Long-lasting protection by live attenuated simian immunodeficiency virus in
cynomolgus monkeys: no detection of reactivation after stimulation with a recall
antigen.
AB - The infection of cynomolgus monkeys with an attenuated simian immunodeficiency
virus (SIV) (C8) carrying a deletion in the nef gene results in a persistent
infection associated with an extremely low viral burden in peripheral blood
mononuclear cells. The aim of this study was to determine (1) the breadth of the
protection after repeated challenges of monkeys with SIV homologous strains of
different pathogenicity, (2) the genotypic stability of the live virus vaccine,
(3) whether the protection might depend on cellular resistance to superinfection,
and (4) whether immunogenic stimuli such as recall antigens could reactivate the
replication of the C8 virus. To address these goals, the monkeys were challenged
at 40 weeks after C8 infection with 50 MID50 of cloned SIVmac251, BK28 grown on
macaque cells. They were protected as indicated by several criteria, including
virus isolation, anamnestic serological responses, and viral diagnostic PCR. At
92 weeks after the first challenge, unfractionated peripheral blood mononuclear
cells from protected monkeys were susceptible to the in vitro infection with
SIVmac32H, spl. At 143 weeks after C8 infection, the four protected monkeys were
rechallenged with 50 MID50 of the pathogenic SIVmac32H, spl grown on macaque
cells. Once again, they were protected. The C8 virus remained genotypically
stable, and depletion of CD4(+) cells was not observed during approximately 3
years of follow-up. In contrast, it was found that the infection with SIVmac32H,
spl induced CD4(+) cell depletion in three of three control monkeys. Of
importance, stimulation with tetanus toxoid, although capable of inducing
specific humoral and T cell proliferative responses, failed to induce a
detectable reactivation of C8 virus.
PMID- 10191195
TI - Gene regulation mediated by interaction between HTLV-1 promoter elements and
transcription factors Tax and CREB.
AB - In this work we examine the role of three genetic control components in the
regulation of HTLV-1 transcription: cyclic AMP-responsive element (CRE)-binding
protein (CREB), the HTLV-1 trans-activator Tax, and the three Tax-responsive
elements (TREs). We demonstrate that the in vivo efficiency of the HTLV-1
promoter basal expression in cell culture depends on the spacing between the
three TRE elements, located at the HTLV-1 LTR (long terminal repeat), whereas the
level of transcription activation mediated by Tax is affected by the number of
TREs. In the presence of only one TRE, the enhancement of expression by Tax is
affected by the distance between the single TRE and the transcription start site.
Following CREB binding to the LTR, additional DNase I hypersensitive sites are
generated in the region between the two distal TREs (I and II), while in the
presence of Tax, such sites are generated also in the region between TREs II and
III. Neither cooperative binding of CREB to the TREs nor preferential binding of
CREB to a particular TRE was observed. Tax binding to the CREB/TRE complex does
not change the DNase I protection pattern. Taken together, these results suggest
that the basal CREB-mediated transcription is determined by the number and the
position of the viral TREs relative to each other. Tax protein stabilizes the
protein/DNA complex and suppresses the spacing limitations, probably by bridging
between the CREB/TRE complexes and the basal initiation transcription complex.
PMID- 10191196
TI - Adenovirus E4 open reading frame 4-induced dephosphorylation inhibits E1A
activation of the E2 promoter and E2F-1-mediated transactivation independently of
the retinoblastoma tumor suppressor protein.
AB - Previous studies have shown that the cell cycle-regulated E2F transcription
factor is subjected to both positive and negative control by phosphorylation.
Here we show that in transient transfection experiments, adenovirus E1A
activation of the viral E2 promoter is abrogated by coexpression of the viral E4
open reading frame 4 (E4-ORF4) protein. This effect does not to require the
retinoblastoma protein that previously has been shown to regulate E2F activity.
The inhibitory activity of E4-ORF4 appears to be specific because E4-ORF4 had
little effect on, for example, E4-ORF6/7 transactivation of the E2 promoter. We
further show that the repressive effect of E4-ORF4 on E2 transcription works
mainly through the E2F DNA-binding sites in the E2 promoter. In agreement with
this, we find that E4-ORF4 inhibits E2F-1/DP-1-mediated transactivation. We also
show that E4-ORF4 inhibits E2 mRNA expression during virus growth. E4-ORF4 has
previously been shown to bind to and activate the cellular protein phosphatase
2A. The inhibitory effect of E4-ORF4 was relieved by okadaic acid, which inhibits
protein phosphatase 2A activity, suggesting that E4-ORF4 represses E2
transcription by inducing transcription factor dephosphorylation. Interestingly,
E4-ORF4 did not inhibit the transactivation capacity of a Gal4-E2F hybrid
protein. Instead, E4-ORF4 expression appears to result in reduced stability of
E2F/DNA complexes.
PMID- 10191197
TI - Regulatable expression of the interferon-induced double-stranded RNA dependent
protein kinase PKR induces apoptosis and fas receptor expression.
AB - PKR is an interferon-induced dsRNA-dependent protein kinase involved in the
antiviral response as well as in cell growth and differentiation. Studies using a
transdominant negative mutant of PKR also have implicated the kinase in tumor
suppression and apoptosis. However, functional studies of PKR have been hampered
by the lack of a suitable expression system. In this study, we used a
tetracycline-regulated inducible system in NIH3T3 cells to investigate the
involvement of PKR in programmed cell death (apoptosis). We show that expression
of wild-type PKR causes apoptosis and correlates with increased mRNA levels for
the Fas receptor, a member of the tumor necrosis family of proteins. Expression
of an inactive form of PKR (K296R) or the vector alone did not induce apoptosis
or elevate Fas mRNA levels. Our results clearly demonstrate that expression of an
active form of PKR triggers apoptosis, possibly through upregulation of the Fas
receptor.
PMID- 10191198
TI - DNA replication specificity and functional E2 interaction of the E1 proteins of
human papillomavirus types 1a and 18 are determined by their carboxyl-terminal
halves.
AB - Replication of most papillomaviruses (PVs) requires the viral-encoded E1 and E2
proteins that bind to the origin of replication (ori) containing the E1- and E2
binding sites and help recruit host replication factors during the initiation of
DNA replication. We studied the ability of heterologous E1 and E2 proteins to
interact in vivo and support replication, using the human papillomavirus (HPV)
types 1a and 18 as model systems. The E1 protein of HPV-1a in combination with
HPV-18 E2 supported high-level replication of various ori plasmids. In contrast,
the HPV-18 E1 protein interacted weakly with HPV-1a E2 during the replication of
ori plasmids. We have previously shown that the E1 protein of HPV-1a alone is
sufficient for replication of HPV-1a ori plasmids, whereas HPV-18 replication
requires both the E1 and E2 proteins. However, in the latter case, E2-binding
sites alone in the absence of the E1-binding site can function as the minimal
ori. Based on the above observations, we generated hybrids between HPV-1a and HPV
18 E1 proteins in an effort to identify their "replication specificity" domains
using a transient replication assay. These hybrids were also used to localize the
domains in the E1 proteins that are involved in their functional interaction with
the E2 protein during replication. Our results suggest that the "replication
specificity" and functional E2 interaction domains of the HPV-1a and HPV-18 E1
proteins are located in their carboxyl-terminal halves.
PMID- 10191199
TI - The genome nucleotide sequence of a contemporary wild strain of measles virus and
its comparison with the classical Edmonston strain genome.
AB - The only complete genome nucleotide sequences of measles virus (MeV) reported to
date have been for the Edmonston (Ed) strain and derivatives, which were isolated
decades ago, passaged extensively under laboratory conditions, and appeared to be
nonpathogenic. Partial sequencing of many other strains has identified >/=15
genotypes. Most recent isolates, including those typically pathogenic, belong to
genotypes distinct from the Edmonston type. Therefore, the sequence of Ed and
related strains may not be representative of those of pathological measles
circulating at that or any time in human populations. Taking into account these
issues as well as the fact that so many studies have been based upon Ed-related
strains, we have sequenced the entire genome of a recently isolated pathogenic
strain, 9301B. Between this recent isolate and the classical Ed strain, there
were 465 nucleotide differences (2.93%) and 114 amino acid differences (2.19%).
Computation of nonsynonymous and synonymous substitutions in open reading frames
as well as direct comparisons of noncoding regions of each gene and
extracistronic regulatory regions clearly revealed the regions where changes have
been permissible and nonpermissible. Notably, considerable nonsynonymous
substitutions appeared to be permissible for the P frame to maintain a high
degree of sequence conservation for the overlapping C frame. However, the cause
and the effect were largely unclear for any substitution, indicating that there
is a considerable gap between the two strains that cannot be filled. The sequence
reported here would be useful as a reference of contemporary wild-type MeV.
PMID- 10191200
TI - Transcription mapping and characterization of 284R and 121R proteins produced
from early region 3 of bovine adenovirus type 3.
AB - We established the transcription map of early region (E) 3 of bovine adenovirus 3
(BAV-3) by Northern blot, S1 nuclease protection assays, cDNA sequencing, and RT
PCR analysis. Five major classes of mRNAs were identified, which shared the 3'
ends. Four classes of mRNAs transcribed from the E3 promoter also shared the 5'
end, while one major class of mRNA transcribed from the major late promoter
contained a tripartite leader sequence at the 5' end. These five transcripts have
the potential to encode four proteins, namely 284R, 121R, 86R, and 82R. To
identify the proteins, rabbit antiserum was prepared using a bacterial fusion
protein encoding 284R or 121R protein. Serum against 284R immunoprecipitated
protein of 26-32 kDa in in vitro translated and transcribed mRNA and three
proteins of 48, 67, and 125 kDa from BAV-3-infected cells. Western blots and
enzymatic digestions confirmed that the 284R protein is a glycoprotein, which
contains only N-linked oligosaccharides, both high mannose (48 kDa) and complex
types (67 kDa). Serum against 121R immunoprecipitated a protein of 14.5 kDa from
in vitro translated and transcribed mRNA and BAV-3-infected cells. Although 121R
protein shows limited sequence similarity to a 14.7-kDa protein of human
adenovirus 5, the 284R protein appears to be unique to BAV-3. Since proteins
encoded by the E3 region appear to influence adenovirus pathogenesis, the 284R
protein may contribute to the unique pathogenic properties of BAV-3.
PMID- 10191201
TI - Multiple sequence-reactive antibodies induced by a single peptide immunization
with hypervariable region 1 of hepatitis C virus.
AB - Hypervariable region 1 (HVR1) of hepatitis C virus (HCV) is known to contain
neutralizing epitopes. We previously found that murine antibodies against HVR1-#6
captured a different isolate, HCV-#7, and cross-reacted with the HVR1 peptide of
HCV-#7. We investigated the inducibility and generality of cross-reaction of
animal anti-HVR1 antibody responses in this study. Anti-HVR1-#7 antibodies, which
were induced in mice and a chimpanzee by immunization, were found to be cross
reactive to HVR1-#6 peptide. Antibody responses against HVR1-#6-1 and HVR1-#7
peptides were detected in 11/165 (6.7%) and 26/165 (15.8%) HCV-infected
individuals, respectively. Nine HVR1 sequences from six individuals, who were
strongly positive for anti-HVR1-#7 antibodies, were only 50-64.5% identical to
that of HVR1-#7. All nine of these HVR1 peptides were reactive to sera from the
six patients and/or to antisera against HVR1-#6 and HVR1-#7 produced in mice and
chimpanzees. Cross-inhibition tests of chimpanzee antisera indicated that a given
species of anti-HVR1 antibodies was reactive to multiple HVR1 sequences. Fine
epitope mapping of polyclonal and monoclonal anti-HVR1 antibodies showed that
conserved subregions in HVR1 sequences determined the observed immunological
cross-reactivity. Our data demonstrate that cross-reacting anti-HVR1 antibodies
are inducible by a single peptide immunization.
PMID- 10191202
TI - Analysis of human lymphotropic T-cell virus type II-like particle production by
recombinant baculovirus-infected insect cells.
AB - The molecular processes involved in retrovirus assembly and budding formation
remain poorly understood. The gag-pro-pol genes of human lymphotropic T-cell
virus type II (HTLV-II) are translated into Gag, Gag-Pro, or Gag-Pro-Pol by
frameshift events. In the present study, we investigated the roles of the gag,
pro, and pol regions of HTLV-II in viral particle formation using recombinant
baculoviruses. In this study we could successfully produce mature HTLV-II viral
particles containing core structures using a construct expressing the entire gag
pro-pol region. We also investigated the role of the pol region in particle
formation. Deletion of the pol region affects viral particle assembly or release
very little, indicating that the gag-pro region is sufficient for viral particle
formation and maturation. Expression of the Gag proteins alone or Gag proteins
with inactivated viral proteases (Pro) resulted in the formation of viral
particles; however, these particles did not contain core structures. These
results suggest the intracellular expression of Gag with Pro of HTLV-II is
essential for the production of mature virus particles, whereas that of Pol is
not.
PMID- 10191203
TI - Comparison of human sera reactivities in immunoblots with recombinant human
herpesvirus (HHV)-8 proteins associated with the latent (ORF73) and lytic (ORFs
65, K8.1A, and K8.1B) replicative cycles and in immunofluorescence assays with
HHV-8-infected BCBL-1 cells.
AB - The development of reliable, sensitive, and specific serological methods for the
detection of human herpesvirus-8 (HHV-8) antibodies is critical for a thorough
understanding of HHV-8 prevalence and pathogenesis. To evaluate the potential
usefulness of HHV-8 proteins in measuring the responses against both latent and
lytic antigens, we selected 1 latent [open reading frame (ORF) 73] antigen and 3
HHV-8 lytic antigens (ORFs 65, K8.1A, and K8.1B) previously identified as
immunogenic [Virology (1998) 243, 208-217]. Full-length genomic ORF 73 and full
length ORFs 65, K8.1A, and K8.1B from the cDNA clones were cloned, expressed in
bacterial and baculovirus-insect cell expression systems, and purified as GST
fusion proteins. These recombinant proteins were used in Western blot reactions
to test sera from 104 human immunodeficiency virus (HIV)+/Kaposi's sarcoma (KS)+
homosexual men, 77 HIV+/KS- homosexual men, and 84 age-matched HIV-/KS- men.
These sera were also tested in immunofluorescence assays (IFAs) with uninduced
and 12-O-tetradecanoylphorbol-13-acetate-induced B cell lymphoma-1 cells to
detect antibodies against latency-associated nuclear antigens (LANA) and
antibodies against lytic antigens (cytoplasmic fluorescence). These sera
exhibited differential reactivities reflecting different titers of antibodies
against HHV-8 proteins, and variable reactivities were seen more commonly with
the sera from HIV-/KS- adult men. In the Western blot assay, 89% (93 of 104) of
HIV+/KS + sera, 60% (46 of 77) of HIV+/KS- sera, and 7% (6 of 84) HIV+/KS- sera
were reactive with both latent and lytic recombinant antigens. Western blot
reactions with ORF 73 protein were more sensitive than LANA-IFA results. The
lytic IFA and lytic Western blot (ORFs 65 and K8.1A) assays were more sensitive
than the ORF 73 Western blots and LANA-IFA. With an exception of 2 sera from the
HIV-/KS- group, all sera positive for lytic IFA antibodies and ORF 65 and K8.1A
antibodies were also positive for latent antibodies. With few exceptions, sera
positive for ORF 65 antibodies were also positive for K8.1A antibodies, and sera
recognized the K8.1A protein more often than the K8.1B protein. There is a high
degree of concordance between IFA and Western blot reactions, suggesting that
this panel of HHV-8 recombinant proteins could detect a majority of the HHV-8
seropositive individuals. These results suggest that IFA followed by confirmation
with the Western blot reactions with a panel of latent and lytic immunogenic
antigens would provide a reliable, sensitive, and specific method for the
detection of HHV-8 antibodies.
PMID- 10191204
TI - Analysis of hepatitis G virus (HGV) RNA, antibody to HGV envelope protein, and
risk factors for blood donors coinfected with HGV and hepatitis C virus.
AB - Serologic, biochemical, and molecular analyses were used to study hepatitis G
virus (HGV), antibody to the HGV envelope protein (anti-E2), risk factors,
clinical significance, and the impact of HGV on coexistent hepatitis C virus
(HCV). Among 329 donors with confirmed HCV infection, 12% were HGV RNA-positive
and 44% were anti-E2-positive (total exposure, 56%). HGV RNA and anti-E2 were
mutually exclusive except in 9 donors (1.5%); 8 of 9 subsequently lost HGV RNA
but anti-E2 persisted. HGV had little impact on alanine aminotransferase,
aspartate aminotransferase, or gamma-glutamyl transpeptidase in donors with HGV
infection alone or those coinfected with HCV. A multivariate analysis showed that
intravenous drug abuse was the leading risk factor for HGV transmission, followed
by blood transfusion, snorting cocaine, imprisonment, and a history of sexually
transmitted diseases. In summary, HGV and HCV infections were frequently
associated and shared common parenteral risk factors; HGV did not appear to cause
hepatitis or to worsen the course of coexistent hepatitis C.
PMID- 10191205
TI - Prevalence and changes in hepatitis C virus genotypes among multitransfused
persons with hemophilia. The Multicenter Hemophilia Cohort Study.
AB - The purpose of this study was to determine hepatitis C virus (HCV) genotypes and
their relationship to HCV RNA levels over time in a cohort of multitransfused
hemophiliacs. Following reverse transcription and polymerase chain reaction
amplification of HCV RNA, the product DNAs were genotyped by using the line probe
assay. HCV RNA was quantified by the branched-chain DNA assay. Genotyping was
done on 109 serum samples from 32 subjects. Genotype 3a had the highest
prevalence (41%), followed by genotypes 1a (31%) and 1b (13%). Changes in
genotypes were observed in 18 (58%) of the subjects >3-15 years of age. Changes
were more common in human immunodeficiency virus (HIV)-positive subjects (13/17)
than in HIV-negative subjects (5/15) (P=.014). HCV RNA increased 30-fold in HIV
positive subjects whose genotypes changed. Consensus nucleotide sequencing
confirmed genotype changes in 2 patients. We conclude that genotype changes are
common in hemophiliacs with chronic HCV, particularly in those who are coinfected
with HIV.
PMID- 10191206
TI - Early acquisition of TT virus (TTV) in an area endemic for TTV infection.
AB - TT virus (TTV) is widely distributed, with high frequencies of viremia in South
America, Central Africa, and Papua New Guinea. The incidence and timing of
infection in children born in a rural area of the Democratic Republic of Congo
was investigated. TTV viremia was detected in 61 (58%) of 105 women attending an
antenatal clinic and in 36 (54%) of 68 infants. Most infants acquired the
infection at >/=3 months postpartum. Surprisingly, TTV infection was detected in
a large proportion of children with TTV-negative mothers (13 [43%] of 30).
Nucleotide sequences of TTV-infected children were frequently epidemiologically
unlinked to variants detected in the mother. These three aspects contrast with
the maternal transmission of hepatitis G virus/GB virus C in this cohort and
suggest an environmental source of TTV infection comparable to hepatitis A virus
and other enterically transmitted infections.
PMID- 10191207
TI - Association of major histocompatibility complex determinants with the development
of symptomatic and asymptomatic genital herpes simplex virus type 2 infections.
AB - The clinical spectrum of herpes simplex virus (HSV) infections, ranging from
asymptomatic to frequently distressing outbreaks, suggests that there may be
immunologic determinants of disease severity that are associated with human
leukocyte antigen (HLA) expression. A controlled, prospective study identified
several major histocompatibility complex (MHC) class I and II antigens whose
frequencies are associated with HSV-2 infection or with frequent symptomatic
genital recurrences. Previous studies were hampered by the inability to
serologically identify patients with asymptomatic HSV-2 infection. Clinical
evaluation and Western blot assay were used to identify 3 subject cohorts: 1 with
no prior HSV infections, 1 with HSV-2 antibodies but no recognized symptoms, and
1 with HSV-2 antibodies and frequent genital recurrences. Statistical comparisons
of HLA frequencies among these cohorts showed associations of HLA-B27 and -Cw2
with symptomatic disease. Also, HLA-Cw4 was significantly associated with HSV-2
infection. These associations indicate that immunologic factors linked to the MHC
influence the risk of HSV-2 infection and disease expression.
PMID- 10191208
TI - The role of interleukin (IL)-2 and IL-4 in herpes simplex virus type 1 ocular
replication and eye disease.
AB - To assess the relative effect of interleukin (IL)-2- and IL-4-dependent immune
responses on herpes simplex virus (HSV)-1 infection, naive, vaccinated, and mock
vaccinated IL-20/0 and IL-40/0 knockout mice were challenged ocularly with HSV-1.
Naive IL-20/0 mice were significantly more susceptible to lethal infection than
IL-40/0 or parental BALB/c mice. Vaccinated, IL-20/0, IL-40/0, and BALB/c mice
induced similar neutralizing antibody titers and were completely protected
against HSV-1-induced death and corneal scarring. Vaccinated and mock-vaccinated
IL-20/0 mice had significantly higher HSV-1 titers in their eyes than BALB/c
mice, while vaccinated and mock-vaccinated IL-40/0 mice had significantly lower
HSV-1 titers in their eyes than BALB/c mice. Recombinant (r) IL-2 treatment of
the IL-20/0 mice significantly reduced ocular HSV-1 replications, but rIL-4
treatment of IL-40/0 mice significantly increased ocular HSV-1 replications. Th1
(IL-2) cytokine responses may help protect mice against ocular HSV-1 challenge
and reduce ocular HSV-1 replication.
PMID- 10191209
TI - Cytomegalovirus induction of interleukin-6 in lung fibroblasts occurs
independently of active infection and involves a G protein and the transcription
factor, NF-kappaB.
AB - Cytomegalovirus (CMV) infection induces the proinflammatory cytokine, interleukin
(IL)-6, which may contribute to the pathology of the infection. In vitro CMV
induction of IL-6 by human lung fibroblasts was studied. The quantity of cytokine
in culture supernatants was maximal 20 h after infection and decreased
thereafter. Transcription of the IL-6 gene and IL-6 protein expression were
equally stimulated by infectious and UV-inactivated virus (CMV-UV). CMV-UV
stimulated IL-6 was inhibited by pyrrolidinedithiocarbamate (an inhibitor of the
transcription factor, NF-kappaB) and by pertussis toxin (suggesting the
involvement of a G protein) and occurred in the absence of CMV immediate-early
antigen transcription. Neutralizing antibodies to IL-1beta or tumor necrosis
factor-alpha did not affect CMV-UV-induced IL-6, but expression was inhibited by
antibody to the CMV attachment glycoprotein. IL-6 production by fibroblasts
occurs independently from productive infection but has characteristics that
suggest a ligand receptor-mediated pathway. This function may be important in
pathology or disease resolution.
PMID- 10191210
TI - Expression of the late cytomegalovirus (CMV) pp150 transcript in leukocytes of
AIDS patients is associated with a high viral DNA load in leukocytes and presence
of CMV DNA in plasma.
AB - The expression of a late cytomegalovirus (CMV) transcript (pp150) was sought in
peripheral blood leukocytes (PBL) of subjects with AIDS and correlated with the
amounts of CMV DNA in PBL and plasma, by means of quantitative polymerase chain
reaction (PCR). The detection of the late CMV transcript was associated with a
high number of CMV DNA copies in PBL (P=.0015) and with a positive CMV PCR assay
in plasma (P<.001). Expression of CMV pp150 mRNA was best predicted by viral DNA
thresholds corresponding to 7058 and 30 copies in PBL and plasma, respectively.
The detection of CMV pp150 mRNA was associated with the presence of CMV disease
in a univariate analysis but not in a multivariate analysis after controlling for
the viral DNA load in PBL. Thus, active viral replication as determined by a high
CMV DNA load in PBL is reflected by expression of the late CMV transcript in the
same cells and by the presence of CMV DNA in plasma.
PMID- 10191211
TI - Restricted low-level human antibody responses against Epstein-Barr virus (EBV)
encoded latent membrane protein 1 in a subgroup of patients with EBV-associated
diseases.
AB - Human antibody responses to latent membrane protein 1 (LMP1) in patients with
Epstein-Barr virus (EBV)-related disease syndromes were analyzed in detail. Only
by immunoblot analysis with purified recombinant LMP1 and by IFA on recombinant
LMP1-expressing insect cells could human antibodies directed against LMP1 be
detected. Low serum levels of LMP1-directed antibodies could be detected in 3 of
8 EBV-positive Hodgkin's disease patients, 3 of 40 nasopharyngeal carcinoma
patients, 2 of 23 Burkitt's lymphoma patients, and 1 of 27 non-Burkitt's lymphoma
patients. No LMP1-directed antibodies could be detected in healthy EBV carriers,
infectious mononucleosis patients, or patients with chronic EBV disease. All sera
contained significant levels of EBV antibodies directed against the
immunodominant EBV proteins and peptides. From this study, it can be concluded
that LMP1 is a protein with a very low immunogenicity for the humoral immune
response in humans.
PMID- 10191212
TI - Antiviral effect and pharmacokinetic interaction between nevirapine and indinavir
in persons infected with human immunodeficiency virus type 1.
AB - Nevirapine and indinavir have the potential of affecting the pharmacokinetics of
each other. In a prospective trial, 24 human immunodeficiency virus (HIV)
infected subjects on stable nucleoside or no therapy were treated with 800 mg of
indinavir every 8 h. After 7 days, 200 mg of nevirapine a day was added for 14
days and then increased to 200 mg twice a day. At day 7 (before nevirapine),
there was a sevenfold difference among the subjects in indinavir area under the
curve (AUC), and there was a significant correlation between indinavir AUC
(r2=0.378, P=.019), minimum plasma concentration (Cmin; r2=0.359, P=.023),
maximum plasma concentration (Cmax; r2=0.340, P=.028), and plasma HIV RNA
decline. Nevirapine significantly reduced median indinavir Cmin (47.5%) and AUC
(27.4%) and, to a lesser extent, Cmax (11%). Plasma HIV RNA values were =20
copies/mL in 10 of 17 (58.8%) subjects at 58 weeks or last visit. These data
suggest that indinavir dosing should be dependent on drug exposure and not on
cotherapy with nevirapine.
PMID- 10191213
TI - Detection of intracellular antigen-specific cytokines in human T cell
populations.
AB - Determination of antigen-specific cytokine responses of T lymphocytes after
vaccination is made difficult by the low frequency of responder cells. In order
to detect these responses, the profile of intracellular cytokines was analyzed
using flow cytometry after antigenic expansion. Peripheral blood mononuclear
cells were stimulated with antigens for 5 days, further expanded with interleukin
(IL)-2, and then restimulated on day 10. Cytokine production was detected by
intracellular staining with monoclonal antibodies after saponin-based
permeabilization. Influenza expansion resulted in specific interferon-gamma (IFN
gamma) production of 6%-20%, with less IL-4 production (0%-2%). Tetanus toxoid
resulted in even greater production. IL-4 and IFN-gamma were produced mainly by
memory cells of the CD45RO+ phenotype. IFN-gamma production was contributed by
both CD4 and CD8 populations. These methods were then applied to a clinical trial
of a candidate human immunodeficiency virus type 1 vaccine. Antigen-specific
increases in IFN-gamma were measured, which corresponded to antibody production,
lymphoproliferation, and skin testing.
PMID- 10191214
TI - Recombinant influenza A virus vaccines for the pathogenic human A/Hong Kong/97
(H5N1) viruses.
AB - Recombinant reassortment technology was used to prepare H5N1 influenza vaccine
strains containing a modified hemagglutinin (HA) gene and neuraminidase gene from
the A/Hong Kong/156/97 and A/Hong Kong/483/97 isolates and the internal genes
from the attenuated cold-adapted A/Ann Arbor/6/60 influenza virus strain. The HA
cleavage site (HA1/HA2) of each H5N1 isolate was modified to resemble that of
"low-pathogenic" avian strains. Five of 6 basic amino acids at the cleavage site
were deleted, and a threonine was added upstream of the remaining arginine. The
H5 HA cleavage site modification resulted in the expected trypsin-dependent
phenotype without altering the antigenic character of the H5 HA molecule. The
temperature-sensitive and cold-adapted phenotype of the attenuated parent virus
was maintained in the recombinant strains, and they grew to 108.5-9.4 EID50/mL in
eggs. Both H5N1 vaccine virus strains were safe and immunogenic in ferrets and
protected chickens against wild-type H5N1 virus challenge.
PMID- 10191215
TI - Enteropathogens and other factors associated with severe disease in children with
acute watery diarrhea in Lima, Peru.
AB - To evaluate enteropathogens and other factors associated with severe disease in
children with diarrhea, 381 children <5 years of age with diarrhea and moderate
to severe dehydration (in-patients) and 381 age-, sex-, and date-of-visit-matched
children with mild diarrhea (out-patients) presenting to a hospital in Peru, were
studied. Rotavirus was detected in 52% of the in-patients and 35% of the out
patients (odds ratio [OR]=2.3, 95% confidence interval [95% CI]= 1.6-3.2); 95% of
the rotaviruses among in-patients were of serotypes G1-G4. The risk of severe
diarrhea was particularly great in children who were not exclusively breast-fed
in early infancy and who also lacked piped water in their homes (for children
with both characteristics OR=6.8, 95% CI=3.6-12.8). The high prevalence of
rotavirus and its association with severe diarrhea underscores the need for
rotavirus vaccines. Interventions to educate mothers and improve access to safe
water should augment the impact of rotavirus vaccines in preventing severe
diarrhea.
PMID- 10191216
TI - Pneumococcus activation of the 5-lipoxygenase pathway and production of
glycoproteins in the middle ear of rats.
AB - Pneumococcal otitis media is associated with the production of potent
inflammatory mediators (leukotrienes), but the mechanism by which pneumococcus
induces production of leukotrienes in the middle ear is poorly understood. In
this study, up-regulation of 2 genes that govern the lipoxygenase pathway, cPLA2
and 5-LOX, was observed in rats following inoculation of pneumococcus into the
middle ear cavity. Expression of cPLA2 was low, and 5-LOX gene expression was not
detected in control animals. Up-regulation of cPLA2 and 5-LOX in middle ear
epithelial cells was accompanied by an increase of high-molecular-weight
glycoproteins in middle ear fluid and cells. These findings suggest that
pneumococcus activates the lipoxygenase pathway by up-regulating expression of
the cPLA2 and 5-LOX genes. This, in turn, may stimulate synthesis and secretion
of high-molecular-weight glycoproteins that facilitate production of fluid in the
middle ear cleft.
PMID- 10191217
TI - Pneumococcal conjugate vaccine primes for polysaccharide-inducible IgG2 antibody
response in children with recurrent otitis media acuta.
AB - Children with frequent recurrent episodes of otitis media may have a deficient
IgG2 antibody response to polysaccharide antigens. Five otitis-prone children
were vaccinated with heptavalent pneumococcal conjugate vaccine. While all had an
IgG1 antibody response to all pneumococcal serotypes included in the conjugate
vaccine, the IgG2 response, especially to serotypes 6B, 9V, 19F, and 23F, was
poor. However, vaccination with a 23-valent polysaccharide vaccine 6 months after
conjugate vaccination induced an 11.5- to 163-fold increase in IgG2 anti
polysaccharide antibody titers. Thus, an IgG2 polysaccharide antibody deficiency
can be overcome by priming with a pneumococcal conjugate vaccine followed by a
booster with a polyvalent polysaccharide vaccine.
PMID- 10191218
TI - Recurrent Staphylococcus aureus bacteremia: pulsed-field gel electrophoresis
findings in 29 patients.
AB - To identify risk factors for relapse among 309 prospectively identified cases of
Staphylococcus aureus bacteremia, patients with recurrent S. aureus bacteremia
were identified, and pulsed-field gel electrophoresis (PFGE) was performed on
isolates from both episodes. PFGE banding patterns from both isolates were
identical in 23 patients, consistent with relapsed infection. Patients with PFGE
confirmed relapse were more likely by both univariate and multivariate analyses
to have an indwelling foreign body (odds ratio [OR]=18.2, 95% confidence interval
[CI]=7. 6-43.6; P<.001), to have received vancomycin therapy (OR=4.1, 95% CI=1.5
11.6; P=.008), or be hemodialysis-dependent (OR=4.1, 95% CI=1. 8-9.3; P=.002)
than patients who did not develop recurrent bacteremia. These results suggest
that recurrent episodes of S. aureus bacteremia are primarily relapses and are
associated with an indwelling foreign body, receiving vancomycin therapy, and
hemodialysis dependence.
PMID- 10191219
TI - Local production of inflammatory mediators in an experimental model of acute
obstructive pyelonephritis.
AB - To investigate bacterial growth and inflammatory mediator release in the early
stage of the immune response, a unilateral acute ascending pyelonephritis was
induced in rats by intrabladder inoculation of Escherichia coli. The infected
left kidney showed a significant bacterial proliferation, local production of
interleukin (IL)-6 and IL-8 as detected by immunocytochemistry, and extensive
destruction of renal parenchyma associated with impressive leukocyte recruitment.
Inducible and constitutive nitric oxide synthases (NOS) were locally expressed,
and a time-dependent increase in urinary secretion of nitric oxide (NO) was seen
that could be blocked by NG-monomethyl-L-arginine. However, there was a
discrepancy between the NO profile in the kidney and urine. The results
demonstrate that in the early stage of acute pyelonephritis kidney tubules
participate actively in the local host response by producing important
inflammatory mediators and that urinary NO levels are not suitable for predicting
renal NOS activity.
PMID- 10191220
TI - Multidrug-resistant human and animal Salmonella typhimurium isolates in France
belong predominantly to a DT104 clone with the chromosome- and integron-encoded
beta-lactamase PSE-1.
AB - Epidemiologic relationships were investigated in 187 ampicillin-resistant
Salmonella typhimurium strains (86 human, 101 animal) from >2000 strains isolated
in 1994. Of 23 resistance patterns, the most frequent (ampicillin [Am],
chloramphenicol [Cm], tetracycline [Tc], streptomycin and spectinomycin [Sm], and
sulfonamides [Su]) was found in 69.5% of human and 64.8% of animal isolates. Four
beta-lactamase genes were identified, blaTEM (24%), blaPSE-1 (78%), and blaSHV
and oxa-2 (each <3%). blaPSE-1 and the integrase gene, intI1, but not blaTEM,
blaSHV or oxa-2, were chromosomeborne and found almost exclusively in the
AmCmTcSmSu strains. In these, polymerase chain reaction mapping revealed two
distinct integrons carrying blaPSE-1 or aadA2. Lysotypes, plasmid profiles, and
restriction fragment length polymorphisms (IS200) were determined for 50
representative isolates and for 3 DT104 strains from the United Kingdom (UK). The
phage type of the PSE-1-producing AmCmTcSmSu strains was 12 atypic,
indistinguishable from that of the DT104 strains. The combined data indicate that
the same multiresistant clone has spread through human and animal ecosystems in
the UK and France.
PMID- 10191221
TI - Ganglioside GM1 mimicry in Campylobacter strains from sporadic infections in the
United States.
AB - To determine whether GM1-like epitopes in Campylobacter species are specific to O
serotypes associated with Guillain-Barre syndrome (GBS) or whether they are
frequent among random Campylobacter isolates causing enteritis, 275 random
enteritis-associated isolates of Campylobacter jejuni were analyzed. To determine
whether GM1-like epitopes in Campylobacter species are specific to O serotypes
associated with Guillan-Barre syndrome (GBS) or whether they are frequent among
random Campylobacter isolates causing enteritis, 275 enteritis-associated
isolates, randomly collected in the United States, were analyzed using a cholera
toxin binding assay [corrected]. Overall, 26.2% of the isolates were positive for
the GM1-like epitope. Of the 36 different O serotypes in the sample, 21 (58.3%)
contained no strains positive for GM1, whereas in 6 serotypes (16.7%), >50% of
isolates were positive for GM1. GBS-associated serotypes were more likely to
contain strains positive for GM1 than were non-GBS-associated serotypes (37.8%
vs. 15.1%, P=.0116). The results suggest that humans are frequently exposed to
strains exhibiting GM1-like mimicry and, while certain serotypes may be more
likely to possess GM1-like epitopes, the presence of GM1-like epitopes on
Campylobacter strains does not itself trigger GBS.
PMID- 10191222
TI - Effect of chronic intermittent administration of inhaled tobramycin on
respiratory microbial flora in patients with cystic fibrosis.
AB - Pseudomonas aeruginosa endobronchial infection causes significant morbidity and
mortality among cystic fibrosis patients. Microbiology results from two
multicenter, double-blind, placebo-controlled trials of inhaled tobramycin in
cystic fibrosis were monitored for longitudinal changes in sputum microbial
flora, antibiotic susceptibility, and selection of P. aeruginosa isolates with
decreased tobramycin susceptibility. Clinical response was examined to determine
whether current susceptibility standards are applicable to aerosolized
administration. Treatment with inhaled tobramycin did not increase isolation of
Burkholderia cepacia, Stenotrophomonas maltophilia, or Alcaligenes xylosoxidans;
however, isolation of Candida albicans and Aspergillus species did increase.
Although P. aeruginosa tobramycin susceptibility decreased in the tobramycin
group compared with that in the placebo group, there was no evidence of selection
for the most resistant isolates to become most prevalent. The definition of
resistance for parenteral administration does not apply to inhaled tobramycin:
too few patients had P. aeruginosa with a tobramycin MIC >/=16 microgram/mL to
define a new break point on the basis of clinical response.
PMID- 10191223
TI - An epidemic of burkholderia cepacia transmitted between patients with and without
cystic fibrosis.
AB - Burkholderia cepacia is an important pathogen in cystic fibrosis (CF) and an
infrequent cause of nosocomial infection in non-CF patients. This report
describes a large hospital outbreak that appeared to involve both patient groups,
a previously unrecognized phenomenon. Ribotype restriction fragment length
polymorphism (RFLP) profiles and pulsed-field gel electrophoresis-resolved
macrochromosomal RFLPs were analyzed, a ribotype-based phylogenic tree was
constructed, and case-control and cohort studies were performed. A single
dominant clone was found in both CF and non-CF groups. Phylogenic analysis
suggests that it has evolved independently and that such highly transmissible
strains can emerge rapidly and randomly. Acquisition risk in the CF patients was
linked to hospitalization (odds ratio=5.47, P=.0158, confidence interval=1. 28
26.86) and was associated with significantly increased mortality rates. Infection
control policies must now consider this threat of transmission between non-CF and
CF patients.
PMID- 10191224
TI - Vertical transmission of Treponema pallidum to various litters and generations of
guinea pigs.
AB - The transmission of congenital syphilis was studied in a 4-generation guinea pig
family with 10 litters and 38 offspring. By use of one or all of the following
tests (ELISA-IgM, polymerase chain reaction, and rabbit infectivity),
transplacental infection was demonstrated through 5 litters and up to 4
generations. Twenty-eight (93%) of 30 animals were positive by >/=1 test, and 2
(7%) were negative by 1 or 3 tests. While transmission of the pathogen appeared
to be unaffected by the maternal acquisition of immunity, signs of smoldering
infection in the young was suggested by the decline in humoral responses in
successive progeny and by unusual rabbit infectivity test results. With each
pregnancy there was a remarkable booster in the maternal humoral response, which
dropped significantly prior to term. These findings shed new light on the
understanding and interpretation of serologic testing during pregnancy and the
perinatal period.
PMID- 10191225
TI - Enhanced capacity of a widespread strain of Mycobacterium tuberculosis to grow in
human macrophages.
AB - To determine whether the extent of spread of Mycobacterium tuberculosis strains
in the community correlated with their capacity to replicate in human
macrophages, intracellular growth rates of M. tuberculosis patient isolates were
measured. Strain 210 caused disease in 43 patients in central Los Angeles, 3
"small-cluster" strains caused disease in 8-23 patients, and 5 "unique" strains
each caused disease in only 1 patient who was positive by sputum acid-fast smear
and spent substantial amounts of time at homeless shelters that were tuberculosis
transmission sites. Strain 210 isolates grew significantly more rapidly than
small-cluster and unique strains in macrophages. All strains elicited production
of similar amounts of tumor necrosis factor-alpha, interleukin (IL)-6, IL-10, and
IL-12 and were equally susceptible to reactive nitrogen intermediates. It was
concluded that the extensive spread of an M. tuberculosis strain correlated with
its capacity to replicate rapidly in human macrophages, which may be a marker of
virulence.
PMID- 10191226
TI - Immunity to placental malaria. I. Elevated production of interferon-gamma by
placental blood mononuclear cells is associated with protection in an area with
high transmission of malaria.
AB - In areas in which malaria is holoendemic, primigravidae and secundigravidae,
compared with multigravidae, are highly susceptible to placental malaria (PM).
The nature of gravidity-dependent immune protection against PM was investigated
by measuring in vitro production of cytokines by placental intervillous blood
mononuclear cells (IVBMC). The results demonstrated that interferon (IFN)-gamma
may be a critical factor in protection against PM: production of this cytokine by
PM-negative multigravid IVBMC was elevated compared with PM-negative primigravid
and secundigravid and PM-positive multigravid cells. Low IFN-gamma responsiveness
to malarial antigen stimulation, most evident in the latter group, was balanced
by increased interleukin (IL)-4 production, suggesting that counter-regulation of
these two cytokines may be a crucial determinant in susceptibility to PM. A
counter-regulatory relationship between IL-10 and tumor necrosis factor-alpha was
also observed in response to malarial antigen stimulation. These data suggest
that elevated production of IFN-gamma, as part of a carefully regulated cytokine
network, is important in the control of PM.
PMID- 10191227
TI - A multi-epitope synthetic peptide and recombinant protein for the detection of
antibodies to Trypanosoma cruzi in radioimmunoprecipitation-confirmed and
consensus-positive sera.
AB - Peptide epitopes of Trypanosoma cruzi have been identified through expression
cloning. A tripeptide (2/D/E) containing three epitopes (TcD, TcE, PEP-2) was
used in ELISA to detect antibodies to T. cruzi in 239 of 240 consensus-positive
sera and 41 of 42 sera confirmed positive by radioimmunoprecipitation assay. The
1 discrepant consensus-positive serum was used to expression-clone a novel gene
that contained a repeat sequence. A peptide corresponding to this sequence,
TcLo1.2, was specific for T. cruzi. This antigen detected the discrepant
consensus-positive serum and enhanced reactivity of low-positive sera in the
tripeptide assay. A branched synthetic peptide, 2/D/E/Lo1.2, or a linear
recombinant, r2/D/E/Lo1.2, realized all of the diagnostic features of the four
epitopes, including the ability to boost reactivity of low-reactive sera. These
studies show that peptides and recombinants containing multiple repeat epitopes
are powerful tools for developing assays for T. cruzi antibody detection and have
direct application in blood screening.
PMID- 10191228
TI - The hookworm platelet inhibitor: functional blockade of integrins GPIIb/IIIa
(alphaIIbbeta3) and GPIa/IIa (alpha2beta1) inhibits platelet aggregation and
adhesion in vitro.
AB - Hookworms, aggressive, blood-feeding, intestinal nematodes, are currently a
leading cause of iron deficiency anemia in the developing world. An inhibitor of
platelet aggregation and adhesion has been partially purified and characterized
from soluble protein extracts of adult Ancylostoma caninum hookworms. This
protein, named the hookworm platelet inhibitor, has an estimated molecular mass
of 15 kDa as determined by size-exclusion chromatography. In addition to blocking
platelet aggregation in response to a variety of agonists, the partially purified
inhibitor also prevents adhesion of resting platelets to immobilized fibrinogen
and collagen. Inhibitory monoclonal antibodies were used to identify specific
blockade of cell surface integrins GPIIb/IIIa (alphaIIbbeta3) and GPIa/IIa
(alpha2beta1), the platelet receptors for fibrinogen and collagen, respectively.
This broad-spectrum anti-platelet activity is also present in excretory and
secretory products of adult worms, suggesting a biologic role for the hookworm
platelet inhibitor in vivo.
PMID- 10191229
TI - Prevalence of TT virus infection in US blood donors and populations at risk for
acquiring parenterally transmitted viruses.
AB - Two overlapping sets of TT virus (TTV)-specific polymerase chain reaction primers
were used to test for presence of TTV, which was found in approximately 10% of US
volunteer blood donors, 13% of commercial blood donors, and 17% of intravenous
drug abusers. The rate of TTV infection among US non-A, non-B, non-C, non-D, non
E hepatitis patients was only 2%. Among commercial blood donors and intravenous
drug abusers, only 1%-3% of the TTV-positive individuals were coinfected with GB
virus C (GBV-C), a parenterally transmitted virus. This suggests that GBV-C and
TTV may have different routes of transmission. Comparison of the sensitivities of
2 TTV polymerase chain reaction (PCR) primer sets showed that the majority of
samples were detected with only 1 of the 2 sets. Therefore, previous studies in
which only a single PCR primer pair was used may have significantly
underestimated the true prevalence of TTV.
PMID- 10191230
TI - Excretion into bile of a novel unenveloped DNA virus (TT virus) associated with
acute and chronic non-A-G hepatitis.
AB - Recently, an unenveloped, single-stranded DNA virus named TT virus (TTV) has been
reported in association with hepatitis of non-A-G etiology. Five patients with
TTV viremia, who received bile drainage or cholecystectomy, were tested for TTV
DNA in bile by polymerase chain reaction with heminested primers. TTV DNA was
detected in bile from all patients; titers were 10-100 times higher than in serum
in 4 and at a comparable level in the remaining 1 patient. TTV DNA was detected
in feces, also, in 1 of the 2 patients tested. The buoyant density of TTV in bile
from 1 tested patient (1.33-1.35 g/cm3) was the same as that in feces (1.32-1.35
g/cm3). TTV may be secreted via bile into feces in a transmissible form and would
spread by a fecal-oral route for deep and wide penetration into the general
population.
PMID- 10191231
TI - Cytomegalovirus (CMV) retinitis activity is accurately reflected by the presence
and level of CMV DNA in aqueous humor and vitreous.
AB - To evaluate the potential of ocular and systemic specimens to provide markers of
active cytomegalovirus (CMV) retinitis, we examined the relationship between
virologic and clinical aspects of CMV infections in AIDS patients with CMV
retinitis. CMV polymerase chain reaction (PCR) analysis of 74 aqueous humor and
vitreous specimens indicated that ocular specimens can provide accurate markers
to differentiate active and inactive CMV retinitis (aqueous or vitreous PCR,
P<.001). Moreover, these markers were superior to extraocular measures, including
plasma PCR (P=.08) and blood and urine CMV cultures (P=.05). A direct correlation
was identified between the quantity of CMV DNA in aqueous humor or vitreous
specimens and the corresponding surface area of active CMV retinitis (r2=.69
and.44, respectively). Thus, qualitative and quantitative PCR-based analyses of
aqueous humor can provide valuable markers of CMV retinitis activity. Such assays
could provide rapid and reliable tools to assist in management of patients with
CMV retinitis in whom the view of the retina is obscured.
PMID- 10191232
TI - Hepatitis C virus is related to progressive liver disease in human
immunodeficiency virus-positive hemophiliacs and should be treated as an
opportunistic infection.
AB - The hypothesis was investigated that hepatitis C virus (HCV) infection behaves
like an opportunistic infection in which progressive liver disease (PLD) is the
principal manifestation. PLD in 81 hemophiliacs coinfected with HCV and human
immunodeficiency virus (HIV) was compared with 53 HIV-seronegative HCV-infected
hemophiliacs. Progression to AIDS and death in 22 HCV/HIV-coinfected hemophiliacs
with PLD was also compared with 59 coinfected hemophiliacs who did not develop
PLD. The risk of PLD occurrence associated with an HIV-positive status was 7.4
(95% confidence interval [CI], 2.2-25.5; Cox model). In the coinfected group, the
risk of PLD occurrence was higher in subjects with severe AIDS-defining
immunodeficiency than in those without (odds ratio, 3. 6; 95% CI, 1.3-10).
Persons with PLD also had a faster progression to AIDS (P=.03, log rank test)
than those without PLD. Thus, as with other chronic resident human viruses, HCV
should be considered another opportunistic pathogen in HIV disease.
PMID- 10191234
TI - Neutralization escape in human immunodeficiency virus type 1-infected long-term
nonprogressors.
AB - Neutralization-escape variants of human immunodeficiency virus type 1 (HIV-1)
were sought in persons who had persistent low virus loads and who remained
asymptomatic for at least 12-16 years of infection without antiretroviral
therapy. Viruses were isolated from 3 persons at two or three time points during
the course of infection and were assessed for neutralization by sequential
autologous serum samples. Virus neutralization was poor or undetectable with
contemporaneous autologous serum but improved with later serum samples for each
person. In particular, later isolates resisted neutralization by autologous serum
samples that neutralized an earlier isolate. Strain-specific neutralizing
antibodies remained detectable for up to 4.2 years without diminishing in titer.
The results demonstrate that neutralization-escape variants arise periodically in
HIV-1-infected long-term nonprogressors.
PMID- 10191233
TI - Genotypic resistance and the treatment of HIV-1 infection in Espirito Santo,
Brazil.
AB - Before December 1997, in Espirito Santo, Brazil, combination antiretroviral
therapy was used without routine virologic or immunologic monitoring. To examine
consequences of therapy in this setting, clinical information, human
immunodeficiency virus type 1 (HIV-1) RNA levels, CD4 cell counts, and protease
and reverse transcriptase sequences were determined for consecutive HIV-1
infected outpatients. Of 48 treatment-naive individuals, 11 were started on
therapy for HIV-related symptoms; however, 44 (92%) had an RNA level >20,000
copies/mL, a CD4 cell count <500/mm3, or symptoms. Eighteen (51%) of 35 patients
on therapy had an RNA level >20,000 copies/mL. Nucleoside-resistance mutations
were observed in 21 (68%) of 31 nucleoside-experienced subjects. Protease
mutations necessary for high-level protease inhibitor (PI) resistance were
present together with permissive mutations in 3 of 10 PI-experienced patients.
Inability to identify high-risk individuals and to detect virologic failure may
limit the effectiveness of antiretroviral drug programs and may promote the
spread of drug resistance where virologic and immunologic monitoring are not
available.
PMID- 10191235
TI - A simple and reproducible method for collecting nasal secretions in frail elderly
adults, for measurement of virus-specific IgA.
AB - The standard method for collection of respiratory secretions, by use of a nasal
wash (NW) to measure virus-specific IgA, is problematic in frail elderly adults.
Therefore, a simplified collection approach using a nasal swab (NS) is described.
NW and NS samples were collected from healthy young and frail elderly adults, and
IgA titers to respiratory syncytial virus (RSV) fusion and attachment
glycoproteins were determined by enzyme immunoassay. Correlation between IgA
titers in NW and NS was excellent for each of the antigens (correlation
coefficients,.71-.93). In addition, NS results were reproducible when frail
elderly subjects were sampled several weeks apart and were nearly equivalent to
results from NW samples. The ability to sample nasal secretions by use of an NS
when an NW is not technically feasible will facilitate the study of mucosal
immunity to RSV as well as the study of mucosal response to candidate RSV
vaccines in frail elderly populations.
PMID- 10191236
TI - A large outbreak of hemolytic uremic syndrome caused by an unusual sorbitol
fermenting strain of Escherichia coli O157:H-.
AB - Escherichia coli O157:H7 does not ferment sorbitol, a factor used to
differentiate it from other E. coli. From December 1995 to March 1996, 28
children with hemolytic uremic syndrome in Bavaria, Germany, were identified;
many had a sorbitol-fermenting (sf) E. coli O157:H- cultured. A case-control
study showed a dose-response relationship between sausage consumption and
illness. A second case-control study showed a relationship between mortadella and
teewurst consumption and illness, particularly during December (mortadella odds
ratio [OR], 10.5, P=.004; teewurst OR, 6.2, P=.02). Twelve sf O157:H- were
characterized to determine clonality and virulence traits. The strains possessed
the Stx2, eae, and EHEC-hlyA genes but were nonhemolytic on blood agar plates.
The O157:H- isolates belonged to phage type 88 and had identical pulsed-field gel
electrophoresis patterns. This outbreak was caused by sf E. coli O157:H-, which
is not detectable by culture on sorbitol MacConkey's agar. Consumption of two
sausages, including a raw beef-containing sausage, was statistically related to
illness.
PMID- 10191237
TI - Dose-related inflammatory effects of intravenous endotoxin in humans: evaluation
of a new clinical lot of Escherichia coli O:113 endotoxin.
AB - The administration of reference endotoxin (Escherichia coli O:113, Lot EC-5) to
humans has been an important means to study inflammation in vivo; however, the
supply of Lot EC-5 is depleted. A new lot of reference endotoxin (Clinical Center
reference endotoxin [CCRE]), derived from the original bulk material extracted
from E. coli O:113, was processed. The effects of 0-, 1-, 2-, and 4-ng/kg doses
of intravenous CCRE and EC-5 were studied in 20 male subjects. CCRE resulted in
dose-related increases in symptoms, temperature (P=. 016), total leukocyte count
(P=.014), tumor necrosis factor-alpha (P=.004), interleukin (IL)-1 receptor
antagonist (P=.004), IL-6 (P=. 005), IL-8 (P=.011), cortisol (P<.05), and C
reactive protein (P=. 04). These responses were attenuated (all P<.012) in
subjects given Lot EC-5 (4 ng/kg) in comparison with those in subjects given
CCRE, showing that, over several years, EC-5 had lost potency. Thus, in healthy
subjects, the magnitude of exposure to CCRE results in a graded dose response of
major components of innate immunity.
PMID- 10191238
TI - Experimental infection of human volunteers with Haemophilus ducreyi does not
confer protection against subsequent challenge.
AB - Two groups of human volunteers were inoculated with 2 doses of live Haemophilus
ducreyi 35000HP. The reinfection group consisted of 7 subjects who previously had
participated in experimental infection with 35000HP to the pustular stage of
disease. The control group consisted of 7 naive subjects. Papules developed at
92.8% (95% confidence interval [CI], 66.1%-99.8%) of sites inoculated with live
bacteria, in the reinfection group, and at 85.7% (95% CI, 57.2%-98. 2%) of sites
in the control group. Sixty-nine percent (95% CI, 36. 8%-90.9%) of papules
evolved into pustules in the reinfection group, compared with 41% (95% CI, 15.2%
72.3%) in the control group. The recovery rates of H. ducreyi from surface
cultures and the histopathology of biopsies obtained from both groups were
similar. Thus, experimental infection to the pustular stage of disease does not
provide protective immunity against subsequent challenge.
PMID- 10191239
TI - Neutrophil response to Neisseria meningitidis: inhibition of adhesion molecule
expression and phagocytosis by recombinant bactericidal/permeability-increasing
protein (rBPI21).
AB - Polymorphonuclear neutrophil (PMNL) activation enhances microbial clearance but
also contributes to the vascular damage and multiorgan failure associated with
severe meningococcal sepsis. By use of a whole blood model of meningococcal
bacteremia, loss of PMNL L-selectin and up-regulation of CD11b was observed in
response to Neisseria meningitidis serogroups B and C, which is followed by
opsonophagocytosis. PMNL priming with either Escherichia coli lipopolysaccharide
(LPS) or FMLP prior to meningococcal challenge resulted in enhancement of both
PMNL L-selectin shedding (1.5- to 4-fold) and phagocytosis (2- to 3-fold).
Blockade of meningococcal LPS lipid A with recombinant bactericidal/permeability
increasing protein (rBPI21) resulted in partial inhibition of the PMNL activation
and phagocytosis response to N. meningitidis. The effect of rBPI21 was reversed
by excess E. coli LPS or FMLP. It is proposed that PMNL priming by N.
meningitidis results in an exaggerated activation and phagocytosis response to
the organism.
PMID- 10191240
TI - Type-specific opsonophagocytosis of group A Streptococcus by use of a rapid
chemiluminescence assay.
AB - A whole-blood chemiluminescence (CL) assay was developed to determine the
presence of type-specific opsonic antibodies against group A streptococcus (GAS).
Convalescent sera with high bactericidal activities against an M-1 serotype were
used to opsonize different M-types of GAS. CL responses were monitored for 20
min, and results were expressed as integral counts/minute per phagocyte. CL
responses of phagocytes incubated with M-1 GAS opsonized with homologous (M-1)
serum were significantly higher than responses of phagocytes incubated with
heterologous (M-3) GAS. Adsorption of convalescent serum against the homologous,
but not the heterologous, strain markedly reduced the CL response, demonstrating
type specificity. The CL assay showed a high correlation with the indirect
bactericidal test (r=0.90). In conclusion, this CL assay is a rapid, highly
sensitive, specific, and reproducible method for quantifying type-specific
opsonic antibodies against GAS and will be a useful tool for future clinical,
basic science, and epidemiological studies.
PMID- 10191241
TI - Comparison between a whole blood interferon-gamma release assay and tuberculin
skin testing for the detection of tuberculosis infection among patients at risk
for tuberculosis exposure.
AB - A new test that measures interferon-gamma (IFN-gamma) release in whole blood
following stimulation with tuberculin has the potential to detect tuberculosis
infection using a single blood draw. The IFN-gamma release assay was compared
with the standard tuberculin skin test (TST) among 467 intravenous drug users at
risk for tuberculosis in urban Baltimore. Among 300 human immunodeficiency virus
(HIV)-seronegative patients, the IFN-gamma release assay was positive in 177
(59%), whereas the TST was positive in 71 (24%), for a percent agreement of 59%
(kappa=26%). Among 167 HIV-seropositive subjects, the IFN-gamma release assay
identified 32 reactors (19%); the TST identified 16 reactors (9.6%), for a
percent agreement of 82% (kappa=28%). The IFN-gamma release assay detected more
reactors than did the TST, but its agreement with TST was weak. As the TST is an
imperfect standard, further evaluation of the IFN-gamma release assay among
uninfected persons and persons with culture-confirmed tuberculosis will be
useful.
PMID- 10191242
TI - Modulation of neutrophil-mediated activity against the pseudohyphal form of
Candida albicans by granulocyte colony-stimulating factor (G-CSF) administered in
vivo.
AB - Renewed interest in neutrophil transfusions has emerged with the development and
clinical use of granulocyte colony-stimulating factor (G-CSF). G-CSF not only
increases neutrophil (polymorphonuclear leukocyte, PMNL) production but also
modulates various physiological properties of PMNL. The effects of G-CSF on PMNL
mediated fungicidal activity were evaluated by administration of G-CSF (300
micrograms/day subcutaneously) to 5 healthy volunteers for 6 days. G-CSF
significantly enhanced PMNL-mediated damage of Candida albicans pseudohyphae by
33% (P=.007) on day 2 and by 44% (P=.04) on day 6 at a 10:1 effector:target
ratio. In contrast, the ability of PMNL to induce damage of hyphae from either
Fusarium solani or Aspergillus fumigatus did not significantly change during the
study period. These data demonstrate that G-CSF administered in vivo modulates
PMNL-mediated fungicidal activity against the pseudohyphal form of C. albicans,
thereby suggesting potential utility of G-CSF as a biologic response-modifying
therapy in some opportunistic fungal infections.
PMID- 10191243
TI - Serum antibodies to Balamuthia mandrillaris, a free-living amoeba recently
demonstrated to cause granulomatous amoebic encephalitis.
AB - Free-living amoebae cause three well-defined disease entities: a rapidly fatal
primary meningoencephalitis, a chronic granulomatous amoebic encephalitis (GAE),
and a chronic amoebic keratitis. GAE occurs in immunocompromised persons.
Recently, another type of free-living amoeba, Balamuthia mandrillaris, has been
shown to cause GAE. The finding that this amoeba has caused infection in some
healthy children has raised the possibility that humans may lack immunity to B.
mandrillaris. Human serum was examined for the presence of surface antibodies
specific for this amoeba by immunofluorescence. Sera from adults contained titers
of 1/64-1/256 of anti-B. mandrillaris antibodies (IgM and IgG classes), which did
not cross-react with other amoebae. Cord blood contained very low antibody
levels, but levels similar to those in adults were seen in serum of 1- to 5-year
old children.
PMID- 10191244
TI - Association between genes of the major histocompatibility complex class II and
the outcome of hepatitis C virus infection.
PMID- 10191245
TI - Reply
PMID- 10191246
TI - Two cases of Enterococcus faecalis bacteremia associated with a hemodialysis
machine.
PMID- 10191247
TI - Circulating leptin during experimental endotoxemia in humans.
PMID- 10191249
TI - Regions 301-303 and 333-339 in the catalytic domain of blood coagulation factor
IX are factor VIII-interactive sites involved in stimulation of enzyme activity.
AB - The contribution of the Factor IX catalytic domain to Factor VIIIa binding has
been evaluated by functional analysis of Factor IX variants with substitutions in
alpha-helix region 333-339 and region 301-303. These regions were found to play a
prominent role in Factor VIIIa-dependent stimulation of Factor X activation, but
do not contribute to the high-affinity interaction with Factor VIIIa light chain.
We propose that complex assembly between Factor IXa and Factor VIIIa involves
multiple interactive sites that are located on different domains of these
proteins.
PMID- 10191250
TI - Identification of the Mg2+-binding site in the P-type ATPase and phosphatase
members of the HAD (haloacid dehalogenase) superfamily by structural similarity
to the response regulator protein CheY.
AB - The large HAD (haloacid dehalogenase) superfamily of hydrolases comprises P-type
ATPases, phosphatases, epoxide hydrolases and L-2-haloacid dehalogenases. A
comparison of the three-dimensional structure of L-2-haloacid dehalogenase with
that of the response regulator protein CheY allowed the assignment of a conserved
pair of aspartate residues as the Mg2+-binding site in the P-type ATPase and
phosphatase members of the superfamily. From the resulting model of the active
site, a conserved serine/threonine residue is suggested to be involved in
phosphate binding, and a mechanism comprising a phosphoaspartate intermediate is
postulated.
PMID- 10191251
TI - Overexpression of an enzymically inactive interleukin-1-receptor-associated
kinase activates nuclear factor-kappaB.
AB - Upon interleukin 1 (IL-1) stimulation, the IL-1-receptor (IL-1R)-associated
kinase (IRAK) is rapidly recruited to the IL-1R complex and undergoes
phosphorylation. Here we demonstrate that recombinant wild-type IRAK (IRAK-WT),
but not a kinase-defective mutant with Asp340 replaced by an asparagine residue
(IRAK-Asp340Asn), is highly phosphorylated and is capable of auto-phosphorylation
in vitro. Overexpression of both IRAK-WT and IRAK-Asp340Asn caused activation of
nuclear factor kappaB, suggesting that the kinase activity of IRAK is not
required outside of the IL-1R complex.
PMID- 10191252
TI - Glucose and thyroid hormone co-regulate the expression of the intestinal fructose
transporter GLUT5.
AB - Expression of the fructose transporter GLUT5 in Caco-2 cells is controlled by the
carbohydrate content of the culture media [Mesonero, Matosin, Cambier, Rodriguez
Yoldi and Brot-Laroche (1995) Biochem. J. 312, 757-762] and by the metabolic
status of the cells [Mahraoui, Takeda, Mesonero, Chantret, Dussaulx, Bell, and
Brot-Laroche (1994) Biochem. J. 301, 169-175]. In this study we show that, in
fully differentiated Caco-2/TC7 cells, thyroid hormone and glucose increase GLUT5
mRNA abundance in a dose-dependent manner. Using Caco-2/TC7 cells stably
transformed with various fragments of the GLUT5 promoter inserted upstream of the
luciferase reporter gene, we localized the sequences that confer 3,3',5-l-tri
iodothyronine (T3)- and/or glucose-sensitivity to the gene. Glucose
responsiveness is conferred by the -272/+41 fragment of the promoter, but it is
only with the -338/+41 region that transcription of the luciferase reporter gene
is stimulated by T3. This 70 bp fragment from position -338 to -272 of the GLUT5
gene is able to confer T3/glucose-responsiveness to the heterologous thymidine
kinase promoter. Electrophoretic-mobility-shift assays demonstrate that thyroid
hormone receptors alpha and beta are expressed in Caco-2/TC7 cells. They further
show that the -308/-290 region of the GLUT5 promoter binds thyroid hormone
receptor/retinoid X receptor heterodimers, and that glucose and/or T3 exert a
deleterious effect on the binding of the nuclear protein complex.
PMID- 10191253
TI - Methylated C-terminal leucine residue of PP2A catalytic subunit is important for
binding of regulatory Balpha subunit.
AB - Methylation of the C-terminal leucine residue (Leu309) of protein
serine/threonine phosphatase 2A catalytic subunit (PP2AC) is known to regulate
catalytic activity in vitro, but the functional consequence(s) of this post
translational modification in the context of the cell remain unclear. Alkali
induced demethylation of PP2AC in purified PP2A heterotrimer (ABalphaC), but not
in purified PP2A heterodimer (AC), indicated that a larger fraction of PP2AC is
carboxymethylated in ABalphaC than in AC. To explore the role of Leu309 in PP2A
holoenzyme assembly, epitope-tagged PP2A catalytic subunit (HA-PP2A) and a mutant
of HA-PP2A containing an alanine residue in place of Leu309 (HA-PP2A-L309A) were
transiently expressed in COS cells. Both recombinant proteins exhibited
serine/threonine phosphatase activity when immunoisolated from COS cell extracts.
HA-PP2A, but not HA-PP2A-L309A, was carboxymethylated in vitro. A chromatographic
analysis of cell extracts indicated that most endogenous PP2AC and HA-PP2A were
co-eluted with the A and Balpha regulatory subunits of PP2A, whereas most HA-PP2A
L309A seemed to elute with the A subunit as a smaller complex or, alternatively,
as free catalytic (C) subunit. The A subunit co-immunoisolated with both tagged
proteins; however, substantially less Balpha subunit co-immunoisolated with HA
PP2A-L309A than with HA-PP2A. These results demonstrate that the reversibly
methylated C-terminal leucine residue of PP2AC is important for Balpha regulatory
subunit binding. Furthermore, the results provide evidence for an
interrelationship between PP2AC carboxymethylation and PP2A holoenzyme assembly.
PMID- 10191255
TI - Aspartate-27 and glutamate-473 are involved in catalysis by Zymomonas mobilis
pyruvate decarboxylase.
AB - Zymomonas mobilis pyruvate decarboxylase (EC 4.1.1.1) was subjected to site
directed mutagenesis at two acidic residues near the thiamin diphosphate cofactor
in the active site. Asp-27 was changed to Glu or Asn, and Glu-473 was mutated to
Asp (E473D) or Gln (E473Q). Each mutant protein was purified to near-homogeneity,
and the kinetic and cofactor-binding properties were compared with those of the
wild-type protein. Despite the very conservative nature of these alterations, all
mutants had a very low, but measurable, specific activity ranging from 0.025%
(E473Q) to 0.173% (E473D) of the wild type. With the exception of E473Q, the
mutants showed small decreases in the affinity for thiamin diphosphate, and
binding of the second cofactor (Mg2+) was also weakened somewhat. With E473Q,
both cofactors seemed to be very tightly bound so that they were not removed by
the treatment that was effective for the wild-type enzyme and other mutant forms.
All mutants showed minor changes in the Km for substrate, but these alterations
did not account for the low activities. These low specific activities,
accompanied by little change in the Km for pyruvate, are consistent with a
quantitative model of the catalytic cycle in which the main effect of the
mutations is to slow the decarboxylation step with a minor change in the rate
constant for pyruvate binding.
PMID- 10191254
TI - Synthesis and assembly of connexins in vitro into homomeric and heteromeric
functional gap junction hemichannels.
AB - The biogenesis of connexins and their assembly into functional gap junction
hemichannels (connexons) was studied with the use of a cell-free
transcription/translation system. Velocity sedimentation on sucrose gradients
showed that a small proportion of connexin (Cx) 26 and Cx32 that were co
translationally translocated into microsomes were oligomers of Cx26 and Cx32.
Chemical cross-linking studies showed that these corresponded to hexameric
connexons. Reconstitution of connexons synthesized in vitro into liposomes
induced permeability properties consistent with the view that open gap junction
hemichannels were produced. By using an immunoprecipitation approach, a
simultaneous translation of Cx26 and Cx32 incorporated into microsomes resulted
in homomeric connexons. However, supplementation of the translation system in
vitro with liver Golgi membranes produced heteromeric connexons constructed of
Cx32 and Cx26, and also resulted in an increased oligomerization especially of
Cx32. All of the connexins analysed were inserted co-translationally into canine
pancreatic microsomal membranes. In addition, Cx26 and Cx43, but not Cx32, were
also inserted into microsomal membranes post-translationally. Analysis of various
connexin constructs in which the cytoplasmic carboxy tails were transposed, the
cytoplasmic tail of Cx43 was truncated or a reporter protein, aequorin, was
attached to the C-terminus showed that tail length was not the major determinant
of the post-translational membrane insertion of connexins.
PMID- 10191256
TI - Protein structure and gene cloning of Syncephalastrum racemosum nuclease.
AB - The complete amino acid sequence of the fungus Syncephalastrum racemosum (Sr-)
nuclease has been delineated on the basis of protein sequencing of the intact
protein and its protease-digested peptides. The resulting 250-residue sequence
shows a carbohydrate side chain attached at Asn134 and two half-cystine residues
(Cys242 and Cys247) cross-linked to form a small disulphide loop. On the basis of
the sequence of Sr-nuclease, a computer search in the sequence database yielded
60% and 48% positional identities with the sequences of Cunninghamella echinulata
nuclease C1 and yeast mitochondria nuclease respectively, and very little
similarity to those of several known mammalian DNases I. Sequence alignment of
the three similar nucleases reveals that the single small disulphide loop is
unchanged but the carbohydrate attachment in Sr-nuclease is absent from the other
two nucleases. Alignment also shows a highly conserved region harbouring Sr
nuclease His85, which is assigned as one of the essential residues in the active
site. The cDNA encoding Sr-nuclease was amplified by using reverse transcriptase
mediated PCR with degenerate primers based on its amino acid sequence.
Subsequently, specific primers were synthesized for use in the 3' and 5' rapid
amplification of cDNA ends (RACE). Direct sequencing of the RACE products led to
the deduction of a 1.1 kb cDNA sequence for Sr-nuclease. The cDNA contains an
open reading frame of 320 amino acid residues including a 70-residue putative
signal peptide and the 250-residue mature protein. Finally, the recombinant Sr
nuclease was expressed in Escherichia coli strain BL21(DE3) in which the
recombinant protein, after solubilization with detergent and renaturation, showed
both DNase and RNase activities. The assignment of His85 to the active site was
further supported by evidence that the mutant protein Sr-nuclease (H85A), in
which His85 was replaced by Ala, was not able to degrade DNA or RNA.
PMID- 10191257
TI - Transmembrane folding of the human erythrocyte anion exchanger (AE1, Band 3)
determined by scanning and insertional N-glycosylation mutagenesis.
AB - The human erythrocyte anion exchanger (AE1, Band 3) contains up to 14
transmembrane segments, with a single site of N-glycosylation at Asn642 in
extracellular (EC) loop 4. Scanning and insertional N-glycosylation mutagenesis
were used to determine the folding pattern of AE1 in the membrane. Full-length
AE1, when expressed in transfected human embryonic kidney (HEK)-293 or COS-7
cells, retained a high-mannose oligosaccharide structure. Scanning N
glycosylation mutagenesis of EC loop 4 showed that N-glycosylation acceptor sites
(Asn-Xaa-Ser/Thr) spaced 12 residues from the ends of adjacent transmembrane
segments could be N-glycosylated. An acceptor site introduced at position 743 in
intracellular (IC) loop 5 that could be N-glycosylated in a cell-free translation
system was not N-glycosylated in transfected cells. Mutations designed to disrupt
the folding of this loop enhanced the level of N-glycosylation at Asn743 in
vitro. The results suggest that this loop might be transiently exposed to the
lumen of the endoplasmic reticulum during biosynthesis but normally folds
rapidly, precluding N-glycosylation. EC loop 4 insertions into positions 428,
484, 754 and 854 in EC loops 1, 2, 6 and 7 respectively were efficiently N
glycosylated, showing that these regions were extracellular. EC loop 4 insertions
into positions 731 or 785 were poorly N-glycosylated, which was inconsistent with
an extracellular disposition for these regions of AE1. Insertion of EC loop 4
into positions 599 and 820 in IC loops 3 and 6 respectively were not N
glycosylated in cells, which was consistent with a cytosolic disposition for
these loops. Inhibitor-affinity chromatography with 4-acetamido-4'
isothiocyanostilbene-2,2'-disulphonate (SITS)-Affi-Gel was used to assess whether
the AE1 mutants were in a native state. Mutants with insertions at positions 428,
484, 599, 731 and 785 showed impaired inhibitor binding, whereas insertions at
positions 754, 820 and 854 retained binding. The results indicate that the
folding of the C-terminal region of AE1 is more complex than originally proposed
and that this region of the transporter might have a dynamic aspect.
PMID- 10191258
TI - Mechanisms of inhibition of lipolysis by insulin, vanadate and peroxovanadate in
rat adipocytes.
AB - Vanadate and peroxovanadate (pV), potent inhibitors of tyrosine phosphatases,
mimic several of the metabolic actions of insulin. Here we compare the mechanisms
for the anti-lipolytic action of insulin, vanadate and pV in rat adipocytes.
Vanadate (5 mM) and pV (0.01 mM) inhibited lipolysis induced by 0.01-1 microM
isoprenaline, vanadate being more and pV less efficient than insulin (1 nM). A
loss of anti-lipolytic effect of pV was observed by increasing the concentration
of isoprenaline and/or pV. pV induced tyrosine phosphorylation of the insulin
receptor and insulin receptor substrate-1 to a greater extent than insulin,
whereas vanadate affected these components little if at all. In addition, only a
higher concentration (0.1 mM) of pV induced the tyrosine phosphorylation of p85,
the 85 kDa regulatory subunit of phosphoinositide 3-kinase (PI-3K). Vanadate
activated PI-3K-independent (in the presence of 10 nM isoprenaline) and PI-3K
dependent (in the presence of 100 nM isoprenaline) anti-lipolytic pathways, both
of which were found to be independent of phosphodiesterase type 3B (PDE3B). pV
(0.01 mM), like insulin, activated PI-3K- and PDE3B-dependent pathways. However,
the anti-lipolytic pathway of 0.1 mM pV did not seem to require insulin receptor
substrate-1-associated PI-3K and was found to be partly independent of PDE3B.
Vanadate and pV (only at 0.01 mM), like insulin, decreased the isoprenaline
induced activation of cAMP-dependent protein kinase. Overall, these results
underline the complexity and the diversity in the mechanisms that regulate
lipolysis.
PMID- 10191259
TI - Cloning and expression of a human choline/ethanolaminephosphotransferase:
synthesis of phosphatidylcholine and phosphatidylethanolamine.
AB - Cholinephosphotransferase catalyses the final step in the synthesis of
phosphatidylcholine (PtdCho) via the Kennedy pathway by the transfer of
phosphocholine from CDP-choline to diacylglycerol. Ethanolaminephosphotransferase
catalyses an analogous reaction with CDP-ethanolamine as the phosphobase donor
for the synthesis of phosphatidylethanolamine (PtdEtn). Together these two enzyme
activities determine both the site of synthesis and the fatty acyl composition of
PtdCho and PtdEtn synthesized de novo. A human
choline/ethanolaminephosphotransferase cDNA (hCEPT1) was cloned, expressed and
characterized. Northern blot analysis revealed one hCEPT1 2.3 kb transcript that
was ubiquitous and not enriched, with respect to actin, in any particular cell
type. The open reading frame predicts a protein (hCEPT1p) of 416 amino acid
residues with a molecular mass of 46550 Da containing seven membrane-spanning
domains. A predicted amphipathic helix resides within the active site of the
enzyme with the final two aspartic residues of the CDP-alcohol phosphotransferase
motif, DG(X)2AR(X)8G(X)3D(X)3D, positioned within this helix. hCEPT1p was
successfully expressed in a full-length, active form in Saccharomyces cerevisiae
cells devoid of endogenous cholinephosphotransferase or
ethanolaminephosphotransferase activities (HJ091, cpt1::LEU2 ept1-). In vitro,
hCEPT1p displayed broad substrate specificity, utilizing both CDP-choline and CDP
ethanolamine as phosphobase donors to a broad range of diacylglycerols, resulting
in the synthesis of both PtdCho and PtdEtn. In vivo, S. cerevisiae cells (HJ091,
cpt1::LEU2 ept1-) expressing hCEPT1 efficiently incorporated both radiolabelled
choline and ethanolamine into phospholipids, demonstrating that hCEPT1p has the
ability to synthesize both choline- and ethanolamine- containing phospholipids in
vitro and in vivo.
PMID- 10191260
TI - Functional expression, quantification and cellular localization of the Hxt2
hexose transporter of Saccharomyces cerevisiae tagged with the green fluorescent
protein.
AB - The Hxt2 glucose transport protein of Saccharomyces cerevisiae was genetically
fused at its C-terminus with the green fluorescent protein (GFP). The Hxt2-GFP
fusion protein is a functional hexose transporter: it restored growth on glucose
to a strain bearing null mutations in the hexose transporter genes GAL2 and HXT1
to HXT7. Furthermore, its glucose transport activity in this null strain was not
markedly different from that of the wild-type Hxt2 protein. We calculated from
the fluorescence level and transport kinetics that induced cells had 1.4x10(5)
Hxt2-GFP molecules per cell, and that the catalytic-centre activity of the Hxt2
GFP molecule in vivo is 53 s-1 at 30 degrees C. Expression of Hxt2-GFP was
induced by growth at low concentrations of glucose. Under inducing conditions the
Hxt2-GFP fluorescence was localized to the plasma membrane. In a strain impaired
in the fusion of secretory vesicles with the plasma membrane, the fluorescence
accumulated in the cytoplasm. When induced cells were treated with high
concentrations of glucose, the fluorescence was redistributed to the vacuole
within 4 h. When endocytosis was genetically blocked, the fluorescence remained
in the plasma membrane after treatment with high concentrations of glucose.
PMID- 10191261
TI - Prediction and experimental testing of Bacillus acidocaldarius thioredoxin
stability.
AB - In order to investigate further the determinants of protein stability, four
mutants of thioredoxin from Bacillus acidocaldarius were designed: K18G, R82E,
K18G/R82E, and D102X, in which the last four amino acids were deleted. The
mutants were constructed on the basis of molecular dynamic studies and the
prediction of the structure of thioredoxin from B. acidocaldarius, performed by a
comparative molecular modelling technique using Escherichia coli thioredoxin as
the reference protein. The mutants obtained by PCR strategy were expressed in E.
coli and then characterized. CD spectroscopy, spectrofluorimetry and
thermodynamic comparative studies permitted comparison of the relative
physicochemical behaviour of the four proteins with that of the wild-type
protein. As predicted for the molecular dynamic analysis at 500 K in vacuo, the
wild-type structure was more stable than that of the mutants; in fact the Tm of
the four proteins showed a decrease of about 15 degrees C for the double and the
truncated mutants, and a decrease of about 12 degrees C for the single mutants. A
difference in the resistance of the proteins to denaturants such as guanidine HCl
and urea was revealed; the wild-type protein always proved to be the most
resistant. The results obtained show the importance of hydrogen bonds and ion
pairs in determining protein stability and confirm that simulation methods are
able to direct protein engineering in site-directed mutagenesis.
PMID- 10191262
TI - Activation of serum- and glucocorticoid-regulated protein kinase by agonists that
activate phosphatidylinositide 3-kinase is mediated by 3-phosphoinositide
dependent protein kinase-1 (PDK1) and PDK2.
AB - The PtdIns(3,4,5)P3-dependent activation of protein kinase B (PKB) by 3
phosphoinositide-dependent protein kinases-1 and -2 (PDK1 and PDK2 respectively)
is a key event in mediating the effects of signals that activate PtdIns 3-kinase.
The catalytic domain of serum- and glucocorticoid-regulated protein kinase (SGK)
is 54% identical with that of PKB and, although lacking the PtdIns(3,4, 5)P3
binding pleckstrin-homology domain, SGK retains the residues that are
phosphorylated by PDK1 and PDK2, which are Thr256 and Ser422 in SGK. Here we show
that PDK1 activates SGK in vitro by phosphorylating Thr256. We also show that, in
response to insulin-like growth factor-1 (IGF-1) or hydrogen peroxide,
transfected SGK is activated in 293 cells via a PtdIns 3-kinase-dependent pathway
that involves the phosphorylation of Thr256 and Ser422. The activation of SGK by
PDK1 in vitro is unaffected by PtdIns(3,4,5)P3, abolished by the mutation of
Ser422 to Ala, and greatly potentiated by mutation of Ser422 to Asp (although
this mutation does not activate SGK itself). Consistent with these findings, the
Ser422Asp mutant of SGK is activated by phosphorylation (probably at Thr256) in
unstimulated 293 cells, and activation is unaffected by inhibitors of PtdIns 3
kinase. Our results are consistent with a model in which activation of SGK by IGF
1 or hydrogen peroxide is initiated by a PtdIns(3,4, 5)P3-dependent activation of
PDK2, which phosphorylates Ser422. This is followed by the PtdIns(3,4,5)P3
independent phosphorylation at Thr256 that activates SGK, and is catalysed by
PDK1. Like PKB, SGK preferentially phosphorylates serine and threonine residues
that lie in Arg-Xaa-Arg-Xaa-Xaa-Ser/Thr motifs, and SGK and PKB inactivate
glycogen synthase kinase-3 similarly in vitro and in co-transfection experiments.
These findings raise the possibility that some physiological roles ascribed to
PKB on the basis of the overexpression of constitutively active PKB mutants might
be mediated by SGK.
PMID- 10191263
TI - Independent regulation of cyclo-oxygenase 2 expression by p42/44 mitogen
activated protein kinases and Ca2+/calmodulin-dependent kinase.
AB - 5-Hydroxytryptamine (5-HT, 'serotonin') is a potent inducer of the early response
gene cyclo-oxygenase 2 (Cox-2; prostaglandin G/H synthase) in mesangial cells.
Protein kinase C (PKC), Ca2+-dependent enzymes and mitogen-activated protein
kinase (p42/44 MAPK) have previously been shown to be essential modules of the
signalling pathway leading from the pertussis-insensitive 5-HT2A receptor to the
induction of Cox-2 mRNA expression. In the present study, PKC activation was
linked to the 5-HT-mediated phosphorylation and thus the activation of p42/44
MAPK: the inhibition of PKC by the specific inhibitor GF109203x prevented p42/44
MAPK activation. Ca2+/calmodulin-dependent (CaM) kinase II delta2 was detected in
mesangial cells by Western blot analysis. The inhibition of CaM kinase by the
inhibitors KN62 or KN93 led to a partial inhibition of 5-HT-induced Cox-2 mRNA
expression and decreased basal, but not PMA-mediated, Cox-2 expression. The 5-HT
mediated activation of MAPK was not decreased by KN62 or KN93, excluding CaM
kinase as a signalling module upstream of p42/44 MAPK. Taken together, these
results indicate a modulatory involvement of CaM kinase in the regulation of 5-HT
mediated Cox-2 mRNA expression in addition to the main pathway that consists of
the activation of PKC and p42/44 MAPK.
PMID- 10191264
TI - Positive and negative regulatory elements in the upstream region of the rat Cu/Zn
superoxide dismutase gene.
AB - Cu/Zn-superoxide dismutase (SOD1) catalyses the dismutation of superoxide
radicals and neutralizes the oxidative effects of various chemicals. Deletion
analysis of the upstream region of the rat SOD1 gene revealed that the promoter
contains a positive regulatory element (PRE) and a negative regulatory element
(NRE), which encompass the regions from -576 to -412 and from -412 to -305
respectively from the site of initiation of transcription. These DNA elements
showed enhancer and silencer activities respectively in the natural context and
in a heterologous promoter system. Using an electrophoretic-mobility-shift assay
and a supershift assay with a specific antibody, the cis-elements of the PRE and
NRE were identified as binding sites for transcription factors Elk1 and YY1 (Ying
Yang 1) respectively. Consistent with the presumed roles of the PRE and NRE, Elk1
increased SOD1 gene transcription about 4-5-fold, whereas YY1 exerted a negative
effect of about 6-fold. Mutations of the Elk1- and YY1-binding sites led to
diminution and elevation respectively of transcriptional activities, both in the
natural context and in heterologous promoter systems. These results suggest that
the transcription factors Elk1 and YY1, binding in the PRE and NRE respectively,
co-ordinate the expression of the SOD1 gene.
PMID- 10191265
TI - A new scorpion toxin (BmK-PL) stimulates Ca2+-release channel activity of the
skeletal-muscle ryanodine receptor by an indirect mechanism.
AB - A peptide toxin isolated from the Chinese scorpion Buthus martensi Karsch (BmK
PL) stimulated Ca2+-release channel activity in both triad membranes and
reconstituted ryanodine receptors partially purified from rabbit skeletal muscle.
In [3H]ryanodine binding experiments, the toxin increased the affinity of
ryanodine for the receptor, from a Kd of 24.3 nM to 2.9 nM, which is an
enhancement similar to that seen with known receptor activators, such as ATP and
high concentrations of KCl. In contrast, toxin enhancement was not observed with
purified receptors, although intrinsic binding activity and stimulation by the
conventional receptor activators were retained. In single channel recordings of
Ca2+-release activity, the toxin increased the open channel probability (Po) from
0.019 to 0.043 (226% of control) in triad preparations. Further toxin enhancement
of Po from 0.07 to 0.37 (529% of control) was observed using partially-purified
receptors in the presence of ATP. When purified receptors were assayed in the
presence of ATP, however, they showed a high value of Po (0.33) and no further
increase was observed following application of the toxin. Results derived from
two different experimental methods consistently suggest that a molecule(s)
required for toxin-induced enhancement is absent from the purified receptor
preparation. Western blot analysis of receptors prepared using three different
protocols showed that triadin was missing from the purified receptor preparation.
The scorpion toxin minimally enhanced Ca2+-release channel activity of cardiac
preparations. From these results, we conclude that the toxin preferentially
increases the activity of skeletal-muscle ryanodine receptors by an indirect
mechanism, possibly binding to associated protein molecule(s). Triadin is a
strong candidate for such a molecule.
PMID- 10191266
TI - Luminal dissociation of Ca2+ from the phosphorylated Ca2+-ATPase is sequential
and gated by Mg2+.
AB - Transport of Ca2+ across the membrane by the Ca2+-ATPase of skeletal muscle
sarcoplasmic reticulum involves the transfer of two Ca2+ ions from a pair of
cytoplasmic sites to a pair of luminal sites, driven by phosphorylation of the
ATPase. The ATPase is inhibited by Mg2+ at alkaline pH values. Inhibition follows
from a decrease in the rate of release of Ca2+ from the phosphorylated ATPase.
Phosphorylation-induced release of Ca2+ from the ATPase is biphasic at alkaline
pH, which is consistent with sequential release of Ca2+ from the phosphorylated
ATPase; the rates of both components decrease with increasing Mg concentration.
The effect of Mg2+ on the slow phase of release follows from the binding of Mg2+
at the empty outer luminal site, vacated by the release of the first Ca2+ ion.
The effect of Mg2+ on the rate of release of the first Ca2+ ion could follow from
binding to a gating site also affecting the binding of Ca2+ to the cytoplasmic
sites.
PMID- 10191267
TI - Intestinal absorption of epoxy-beta-carotenes by humans.
AB - An increased intake of fruits and vegetables has been shown to be associated with
reduced risk of cancer. In epidemiological studies, supplements of beta-carotene,
which is abundant in fruits and vegetables, were not found to be beneficial in
reducing the incidence of lung cancer in high-risk groups. Epoxycarotenoids are
abundant in nature. 5,6-Epoxy-beta-carotene was much more active than beta
carotene in the induction of differentiation of NB4 cells [Duitsman, Becker,
Barua and Olson (1996) FASEB J. 10, A732]. Epoxycarotenes may, therefore, have
protective effects against cancer. In order to do this, however, epoxycarotenoids
must be absorbed by the human body. There is no evidence that epoxycarotenoids,
despite their abundance in dietary fruits and vegetables, are absorbed by humans.
In this paper, it is demonstrated that orally administered dietary or synthetic
epoxy-beta-carotenes are absorbed by humans, as indicated by their appearance in
the circulating blood.
PMID- 10191268
TI - Inhibition of the peroxidative degradation of haem as the basis of action of
chloroquine and other quinoline antimalarials.
AB - The malaria parasite feeds by degrading haemoglobin in an acidic food vacuole,
producing free haem moieties as a by-product. The haem in oxyhaemoglobin is
oxidized from the Fe(II) state to the Fe(III) state with the consequent
production of an equimolar concentration of H2O2. We have analysed the fate of
haem molecules in Plasmodium falciparum-infected erythrocytes and have found that
only about one third of the haem is polymerized to form haemozoin. The remainder
appears to be degraded by a non-enzymic process which leads to an accumulation of
iron in the parasite. A possible route for degradation of the haem is by reacting
with H2O2, and we show that, under conditions designed to resemble those found in
the food vacuole, i.e., at pH5.2 in the presence of protein, free haem undergoes
rapid peroxidative decomposition. Chloroquine and quinacrine are shown to be
efficient inhibitors of the peroxidative destruction of haem, while epiquinine, a
quinoline compound with very low antimalarial activity, has little inhibitory
effect. We also show that chloroquine enhances the association of haem with
membranes, while epiquinine inhibits this association, and that treatment of
parasitized erythrocytes with chloroquine leads to a build-up of membrane
associated haem in the parasite. We suggest that chloroquine exerts its
antimalarial activity by causing a build-up of toxic membrane-associated haem
molecules that eventually destroy the integrity of the malaria parasite. We have
further shown that resistance-modulating compounds, such as chlorpromazine,
interact with haem and efficiently inhibit its degradation. This may explain the
weak antimalarial activities of these compounds.
PMID- 10191269
TI - Roles of key active-site residues in flavocytochrome P450 BM3.
AB - The effects of mutation of key active-site residues (Arg-47, Tyr-51, Phe-42 and
Phe-87) in Bacillus megaterium flavocytochrome P450 BM3 were investigated.
Kinetic studies on the oxidation of laurate and arachidonate showed that the side
chain of Arg-47 contributes more significantly to stabilization of the fatty acid
carboxylate than does that of Tyr-51 (kinetic parameters for oxidation of
laurate: R47A mutant, Km 859 microM, kcat 3960 min-1; Y51F mutant, Km 432 microM,
kcat 6140 min-1; wild-type, Km 288 microM, kcat 5140 min-1). A slightly increased
kcat for the Y51F-catalysed oxidation of laurate is probably due to decreased
activation energy (DeltaG) resulting from a smaller DeltaG of substrate binding.
The side chain of Phe-42 acts as a phenyl 'cap' over the mouth of the substrate
binding channel. With mutant F42A, Km is massively increased and kcat is
decreased for oxidation of both laurate (Km 2. 08 mM, kcat 2450 min-1) and
arachidonate (Km 34.9 microM, kcat 14620 min-1; compared with values of 4.7
microM and 17100 min-1 respectively for wild-type). Amino acid Phe-87 is critical
for efficient catalysis. Mutants F87G and F87Y not only exhibit increased Km and
decreased kcat values for fatty acid oxidation, but also undergo an irreversible
conversion process from a 'fast' to a 'slow' rate of substrate turnover [for F87G
(F87Y)-catalysed laurate oxidation: kcat 'fast', 760 (1620) min-1; kcat 'slow',
48.0 (44.6) min-1; kconv (rate of conversion from fast to slow form), 4.9 (23.8)
min-1]. All mutants showed less than 10% uncoupling of NADPH oxidation from fatty
acid oxidation. The rate of FMN-to-haem electron transfer was shown to become
rate-limiting in all mutants analysed. For wild-type P450 BM3, the rate of FMN-to
haem electron transfer (8340 min-1) is twice the steady-state rate of oxidation
(4100 min-1), indicating that other steps contribute to rate limitation. Active
site structures of the mutants were probed with the inhibitors 12
(imidazolyl)dodecanoic acid and 1-phenylimidazole. Mutant F87G binds 1
phenylimidazole >10-fold more tightly than does the wild-type, whereas mutant
Y51F binds the haem-co-ordinating fatty acid analogue 12-(imidazolyl)dodecanoic
acid >30-fold more tightly than wild-type.
PMID- 10191270
TI - Biophysical activity of an artificial surfactant containing an analogue of
surfactant protein (SP)-C and native SP-B.
AB - Natural surfactant preparations containing phospholipids and the hydrophobic
surfactant proteins B and C (SP-B and SP-C) are effective in the treatment of
respiratory distress syndrome in premature infants. The limited supply, and the
risk of infectious agents and immunological reactions have promoted the
evaluation of synthetic peptides in surfactant preparations. However, the folding
of synthetic SP-C into an alpha-helix is inefficient and alpha-helical SP-C
analogues with Val-->Leu substitutions form oligomers. In order to circumvent
these problems we have synthesized an SP-C analogue, named SP-C(LKS), which
differs from SP-C mainly by the exchange of most of the Val residues in positions
16-28 with Leu residues to promote an alpha-helical conformation, and by the
introduction of Lys residues at positions 17, 22 and 27 in order to locate
positive charges around the helical circumference and thereby avoid self
polymerization. CD spectroscopy showed a spectrum typical for alpha-helical
peptides and SDS/PAGE disclosed a single band. The biophysical activity of
artificial surfactant preparations containing SP-C(LKS) and phospholipids, with
and without native SP-B, was measured using a Wilhelmy balance and a pulsating
bubble surfactometer. SP-C(LKS) (3%, w/w) in a mixture of 1, 2-dipalmitoyl-sn
glycero-3-phosphocholine (DPPC)/phosphatidylglycerol/palmitic acid (68:22:9, by
wt.) suspended in 150 mM NaCl, showed rapid spreading at the air-liquid interface
and produced a surface tension of <1 mN/m at minimum bubble size (gammamin) and
42 mN/m at maximum bubble size (gammamax) in the pulsating bubble surfactometer.
The addition of 2% (w/w) SP-B to the preparation reduced the maximum surface
tension to 33-35 mN/m, i.e. both gammamin and gammamax values were similar to
those of natural surfactant preparations. Optimal in vitro characteristics were
also obtained from a preparation containing SP-C(LKS), SP-B, DPPC and
phosphatidylglycerol, i.e. when palmitic acid was omitted from the lipid mixture.
SP-B containing surfactant preparations made up in Hepes buffer at pH 6.9,
instead of in 150 mM NaCl, had similar biophysical activity provided that
palmitic acid was omitted, but decreased activity in the presence of palmitic
acid.
PMID- 10191272
TI - N-glycosylation requirements for the AT1a angiotensin II receptor delivery to the
plasma membrane.
AB - The purpose of this work was to investigate the role of N-glycosylation in the
expression and pharmacological properties of the the rat AT1a angiotensin II
(AII) receptor. Glycosylation-site suppression was carried out by site-directed
mutagenesis (Asn-->Gln) of Asn176 and Asn188 (located on the second extracellular
loop) and by the removal of Asn4 at the N-terminal end combined with the
replacement of the first four amino acids by a 10 amino acid peptide epitope (c
Myc). We generated seven possible N-glycosylation-site-defective mutants, all
tagged at their C-terminal ends with the c-Myc epitope. This double-tagging
strategy, associated with photoaffinity labelling, allowed evaluation of the
molecular masses and immunocytochemical cellular localization of the various
receptors transiently expressed in COS-7 cells. We showed that: (i) each of the
three N-glycosylation sites are utilized in COS-7 cells; (ii) the mutant with
three defective N-glycosylation sites was not (or was very inefficiently)
expressed at the plasma membrane and accumulated inside the cell at the
perinuclear zone; (iii) the preservation of two sites allowed normal receptor
delivery to the plasma membrane, the presence of only Asn176 ensuring a behaviour
similar to that of the wild-type receptor; and (iv) all expressed receptors
displayed unchanged pharmacological properties (Kd for 125I-sarcosine1-AII;
sarcosine1-AII-induced inositol phosphate production). These results demonstrate
that N-glycosylation is required for the AT1 receptor expression. They are
discussed in the light of current knowledge of membrane-protein maturation and
future prospects of receptor overexpression for structural studies.
PMID- 10191271
TI - Molecular analysis of two closely related mouse aldehyde dehydrogenase genes:
identification of a role for Aldh1, but not Aldh-pb, in the biosynthesis of
retinoic acid.
AB - Mammalian class I aldehyde dehydrogenase (ALDH1) has been implicated as a retinal
dehydrogenase in the biosynthesis of retinoic acid, a modulator of gene
expression and cell differentiation. As the first step towards studying the
regulation of ALDH1 and its physiological role in the biosynthesis of retinoic
acid, mouse ALDH1 cDNA and genomic clones have been characterized. During the
cloning process, an additional closely related gene was also isolated and named
Aldh-pb, owing to its high amino acid sequence identity (92%) with the rat
phenobarbitol-inducible ALDH protein (ALDH-PB). Aldh1 spans about 45 kb in
length, whereas Aldh-pb spans about 35 kb. Both genes are composed of 13 exons,
and the positions of all the exon/intron boundaries are conserved with those of
human ALDH1. The promoter regions of Aldh1 and Aldh-pb demonstrate high sequence
similarity with those of human ALDH1 and rat ALDH-PB. Expression of Aldh1 and
Aldh-pb is tissue-specific, with mRNAs for both genes being found in the liver,
lung and testis, but not in the heart, spleen or muscle. Expression of Aldh-pb,
but not Aldh1, was also detected at high levels in the kidney. Aldh1 and Aldh-pb
encode proteins of 501 amino acids with 90% positional identity. To examine the
relative roles of these two enzymes in retinoic acid synthesis in vivo, Xenopus
embryos were injected with mRNAs encoding these enzymes to assay the effect on
conversion of endogenous retinal into retinoic acid. Injection of ALDH1, but not
ALDH-PB, mRNA stimulated retinoic acid synthesis in Xenopus embryos at the
blastula stage. Thus our results indicate that Aldh1 can function in retinoic
acid synthesis under physiological conditions, but that the closely related Aldh
pb does not share this property.
PMID- 10191273
TI - Identification and characterization of Saccharomyces cerevisiae yapsin 3, a new
member of the yapsin family of aspartic proteases encoded by the YPS3 gene.
AB - A new aspartic protease from Saccharomyces cerevisiae, with a high degree of
similarity with yapsin 1 and yapsin 2 and a specificity for basic residue
cleavage sites of prohormones, has been cloned. This enzyme was named yapsin 3.
Expression of a C-terminally truncated non-membrane anchored yapsin 3 in yeast
yielded a heterogeneous protein between 135-200 kDa which, upon treatment with
endoglycosidase H, migrated as a 60 kDa form. Amino-acid analysis of the N
terminus of expressed yapsin 3 revealed two different N-terminal residues, serine
48 and phenylalanine-54, which followed a dibasic and a monobasic residue
respectively. Cleavage of several prohormones by non-anchored yapsin 3 revealed a
specificity distinct from that of yapsin 1.
PMID- 10191274
TI - Monomeric (glycine-proline-hydroxyproline)10 repeat sequence is a partial agonist
of the platelet collagen receptor glycoprotein VI.
AB - We have previously reported that a triple-helical, collagen-related peptide (CRP;
also known as CRP-XL) containing a glycine-proline-hydroxyproline (GPP*) repeat
motif and cross-linked through cysteine residues at its N-terminus and C-terminus
is a powerful stimulus of platelet aggregation and secretion through the surface
receptor glycoprotein VI (GPVI). The activation of platelets is associated with
tyrosine phosphorylation of the tyrosine kinase Syk and phospholipase C gamma2
(PLCgamma2). We now report that the non-cross-linked backbone of CRP, monomeric
CRP (mCRP), stimulates the tyrosine phosphorylation of Syk and PLCgamma2 in
platelets and induces the weak secretion of [3H]5-hydroxytryptamine ([3H]5-HT)
and aggregation. The action of mCRP does not seem to be due to spontaneous cross
linking, because alkylation of the cysteine residues leads to an increase in
activity. The tripeptide backbone of CRP, GPP*10 (in which P* represents
hydroxyproline) also stimulates platelet shape change and the weak tyrosine
phosphorylation of Syk and PLCgamma2, but is unable to induce aggregation or
secretion. The monomeric peptides partly inhibit the release of [3H]5-HT by CRP,
suggesting that they are partial agonists of the collagen receptor GPVI. These
results demonstrate that GPP* present as a repeat motif is sufficient to activate
the platelet collagen receptor GPVI but that the cross-linking of monomers brings
about an increase in activity.
PMID- 10191275
TI - Calcium-binding protein S100A7 and epidermal-type fatty acid-binding protein are
associated in the cytosol of human keratinocytes.
AB - Expression of epidermal-type fatty acid-binding protein (E-FABP) and S100A7 has
previously been shown to be elevated in psoriatic skin, a disease characterized
by abnormal keratinocyte differentiation. However, no causal relationship between
the up-regulation of these proteins and the disease has been shown. E-FABP is
thought to be involved in cytosolic fatty acid (FA) transport, whereas the role
of S100A7 is still unknown. In this report, we show by overlay assays that E
FABP, immobilized on nitrocellulose, is able to capture S100A7 from cytosolic
psoriatic protein extracts and vice versa, suggesting the formation of a complex
between the two proteins. Using purified E-FABP and S100A7, the complex can be
reconstituted only in presence of EDTA. Moreover, we show that increased EDTA
concentrations in psoriatic cytosolic protein extracts enhance complex formation.
Partial complex disruption was obtained by the addition of physiological
concentrations of Zn2+ (0.1 mM), whereas Ca2+ at 5 mM and Mg2+ at 30 mM had no
effect. On the other hand, high Ca2+ concentrations (30 mM) resulted in partial
complex disruption. Oleic acid-binding properties were observed for free E-FABP
and the complex E-FABP-S100A7, but not for free S100A7. By using confocal
microscopy we show that S100A7 and E-FABP are co-localized in the cytoplasm of
differentiating keratinocytes from lesional psoriatic skin. These data indicate
that formation of the E-FABP-S100A7 complex and its FA-binding function might be
regulated at least by bivalent cations.
PMID- 10191276
TI - Cellulose as an inert matrix for presenting cytokines to target cells: production
and properties of a stem cell factor-cellulose-binding domain fusion protein.
AB - A chimaera of stem cell factor (SCF) and a cellulose-binding domain from the
xylanase Cex (CBDCex) effectively immobilizes SCF on a cellulose surface. The
fusion protein retains both the cytokine properties of SCF and the cellulose
binding characteristics of CBDCex. When adsorbed on cellulose, SCF-CBDCex is up
to 7-fold more potent than soluble SCF-CBDCex and than native SCF at stimulating
the proliferation of factor-dependent cell lines. When cells are incubated with
cellulose-bound SCF-CBDCex, activated receptors and SCF-CBDCex co-localize on the
cellulose matrix. The strong binding of SCF-CBDCex to the cellulose surface
permits the effective and localized stimulation of target cells; this is
potentially significant for long-term perfusion culturing of factor-dependent
cells. It also permits the direct analysis of the effects of surface-bound
cytokines on target cells.
PMID- 10191277
TI - Association of polo-like kinase with alpha-, beta- and gamma-tubulins in a stable
complex.
AB - The polo-like kinase (Plk) family has been shown to have an important role in the
regulation of the cell-division cycle, especially in organization of the spindle
structure, in species from fungi to humans. Recent reports have demonstrated that
in mammalian cells Plk is associated with components of the anaphase-promoting
complex and a peptidyl-prolyl isomerase, Pin1. To characterize a putative Plk
containing complex, we fractionated mitotic cell lysates on a gel-filtration
column. The Plk complex was eluted from the column at molecular sizes ranging
from 669 to 2500 kDa in the presence of detergent and high concentrations of
salt. Specific associations of Plk with alpha-, beta- and gamma-tubulins in both
interphase and mitotic cells were shown by reciprocal immunoprecipitations and
immunoblottings and were independent of the microtubule polymerization state,
whereas binding assays in vitro indicated that Plk interacts with alpha- and beta
tubulins directly. In addition, mitotic Plk was able to phosphorylate associated
tubulins in vitro. Finally, we show that the kinase domain of the Plk molecule is
both required and sufficient for its binding to tubulins in vivo. The specific
interaction between Plk and tubulins might provide a molecular basis for the
physiological functions of Plk in regulating the cell cycle, particularly in
establishing the normal bipolar spindle.
PMID- 10191278
TI - Insulin-like growth factor (IGF-I) induces myotube hypertrophy associated with an
increase in anaerobic glycolysis in a clonal skeletal-muscle cell model.
AB - Insulin-like growth factor-I (IGF-I) is an important autocrine/paracrine mediator
of skeletal-muscle growth and development. To develop a definitive cultured cell
model of skeletal-muscle hypertrophy, C2C12 cells were stably transfected with
IGF-I and clonal lines developed and evaluated. Quantitative morphometric
analysis showed that IGF-I-transfected myotubes had a larger area (2381+/-60
micrometer2 versus 1429+/-39 micrometer2; P<0.0001) and a greater maximum width
(21.4+/-0.6 micrometer versus 13.9+/-0.3 micrometer; P<0.0001) than control C2C12
myotubes, independent of the number of cell nuclei per myotube. IGF-I-transfected
myotubes had higher levels of protein synthesis but no difference in DNA
synthesis when compared with control myotubes, indicating the development of
hypertrophy rather than hyperplasia. Both lactate dehydrogenase and alanine
aminotransferase activities were increased (3- and 5-fold respectively), and
total lactate levels were higher (2.3-fold) in IGF-I-transfected compared with
control myotubes, indicating an increase in anaerobic glycolysis in the
hypertrophied myotubes. However, expression of genes involved in skeletal-muscle
growth or hypertrophy in vivo, e.g. myocyte nuclear factor and myostatin, was not
altered in the IGF-I myotubes. Finally, myotube hypertrophy could also be induced
by treatment of C2C12 cells with recombinant IGF-I or by growing C2C12 cells in
conditioned media from IGF-I-transfected cells. This quantitative model should be
uniquely useful for elucidating the molecular mechanisms of skeletal-muscle
hypertrophy.
PMID- 10191279
TI - Down-regulation of types I, II and III inositol 1,4,5-trisphosphate receptors is
mediated by the ubiquitin/proteasome pathway.
AB - Activation of certain phosphoinositidase-C-linked cell-surface receptors is known
to cause an acceleration of the proteolysis of inositol 1,4,5-trisphosphate
[Ins(1,4,5)P3] receptors and, thus, lead to Ins(1,4,5)P3-receptor down
regulation. In the current study we have sought to determine whether the
ubiquitin/proteasome pathway is involved in this adaptive response. The data
presented show (i) that activation of phosphoinositidase-C-linked receptors
causes Ins(1,4,5)P3-receptor ubiquitination in a range of cell types (AR4-2J
cells, INS-1 cells and rat cerebellar granule cells), (ii) that the Ins(1,4,5)P3
receptor down-regulation induced by activation of these receptors is blocked by
proteasome inhibitors, (iii) that all known Ins(1,4,5)P3 receptors (types I, II
and III) are substrates for ubiquitination, (iv) that ubiquitination occurs while
Ins(1,4,5)P3 receptors are membrane-bound, (v) that Ins(1,4, 5)P3-receptor
ubiquitination and down-regulation are stimulated only by those agonists that
elevate Ins(1,4,5)P3 concentration persistently, and (vi) that a portion of
cellular Ins(1,4,5)P3 receptors (those that are not type-I-receptor-associated)
can be resistant to ubiquitination and degradation. In total these data indicate
that the ubiquitin/proteasome pathway mediates Ins(1,4, 5)P3-receptor down
regulation and suggest that ubiquitination is stimulated by the binding of
Ins(1,4,5)P3 to its receptor.
PMID- 10191280
TI - Association of tubulin carboxypeptidase with microtubules in living cells.
AB - Tubulin carboxypeptidase is the enzyme that releases the C-terminal tyrosine from
alpha-tubulin, converting tyrosine-terminated (Tyr) to detyrosinated (Glu)
tubulin. The present study demonstrates that this enzyme is associated with
microtubules in living cells. We extracted cultured cells (COS-7) with Triton X
100 under microtubule-stabilizing conditions and found tubulin carboxypeptidase
activity in the cytoskeleton fraction. We ruled out, by using several control
experiments, the possibility that this result was due to contamination of the
isolated cytoskeletons by non-associated proteins contained in the detergent
fraction or to an artifact in vitro during the extraction procedure. The
associated carboxypeptidase activity showed characteristics similar to those of
brain tubulin carboxypeptidase and different from those of pancreatic
carboxypeptidase A. In comparison with cultures at confluence, those at low cell
density contained small (if any) amounts of carboxypeptidase activity associated
with microtubules. In addition, the enzyme was shown to be associated only with
cold-labile microtubules. The tubulin carboxypeptidase/microtubule association
was also demonstrated in Chinese hamster ovary, NIH 3T3 and PC12 cells.
Interestingly, this association was not observed in cultured embryonic brain
cells. Our results demonstrate that tubulin carboxypeptidase is indeed associated
with microtubules in living cells. Furthermore, the findings that this
association occurs with a subset of microtubules and that its magnitude depends
on the degree of confluence of the cell culture indicate that it could be part of
the mechanism that regulates the tyrosination state of microtubules.
PMID- 10191281
TI - Specificity of human tissue kallikrein towards substrates containing Phe-Phe pair
of amino acids.
AB - We have explored in detail the determinants of specificity for the hydrolysis by
human tissue kallikrein (hK1) of substrates containing the Phe-Phe amino acid
pair, after which hK1 cleaves kallistatin (human kallikrein-binding protein), a
specific serpin for this protease, as well as somatostatin 1-14. Internally
quenched fluorogenic peptides were synthesized with the general structure Abz
peptidyl-EDDnp [Abz, o-aminobenzoic acid; EDDnp, N-(2, 4
dinitrophenyl)ethylenediamine], based on the natural reactive-centre loop
sequence of kallistatin from P9 to P'13, and the kinetic parameters of their
hydrolysis by hK1 were determined. All these peptides were cleaved after the Phe
Phe pair. For comparison, we have also examined peptides containing the reactive
centre loop sequences of human protein-C inhibitor (PCI) and rat kallikrein
binding protein, which were hydrolysed after Phe-Arg and Leu-Lys bonds,
respectively. Hybrid peptides containing kallistatin-PCI sequences showed that
the efficiency of hK1 activity on the peptides containing kallistatin and PCI
sequences depended on both the nature of the P1 amino acid as well as on residues
at the P- and P'-sides. Moreover, we have made systematic modifications on the
hydrophobic pair Phe-Phe, and on Lys and Ile at the P3 and P4 positions according
to the peptide substrate, Abz-AIKFFSRQ-EDDnp. All together, we concluded that
tissue kallikrein was very effective on short substrates that are cleaved after
the Phe-Arg pair; however, hydrolysis after Phe-Phe or other hydrophobic pairs of
amino acids was more restrictive, requiring additional enzyme-substrate
interaction and/or particular substrate conformations.
PMID- 10191282
TI - Effect of phospholipase A2 digestion on the conformation and lysine/fibrinogen
binding properties of human lipoprotein[a].
AB - In vitro hydrolysis of human lipoprotein[a] (Lp[a]) by phospholipase A2 (PLA2)
decreased the phosphatidylcholine (PC) content by 85%, but increased
nonesterified fatty acids 3.2-fold and lysoPC 12.9-fold. PLA2-treated Lp[a] had a
decreased molecular weight, increased density, and greater electronegativity on
agarose gels. In solution, PLA2-Lp[a] was a monomer, and when assessed by
sedimentation velocity it behaved like untreated Lp[a], in that it remained
compact in NaCl solutions but assumed the extended form in the presence of 6
amino hexanoic acid, which was shown previously to have an affinity for the
apo[a] lysine binding site II (LBS II) comprising kringles IV5-8. We interpreted
our findings to indicate that PLA2 digestion had no effect on the reactivity of
this site. This conclusion was supported by the results obtained from lysine
Sepharose and fibrinogen binding experiments, in the presence and absence of
Tween 20, showing that phospholipolysis had no effect on the reactivity of the
LBS-II domain. A comparable binding behavior was also exhibited by the free
apo[a] derived from each of the two forms of Lp[a]. We did observe a small
increase in affinity of PLA2-Lp[a] to lysine Sepharose and attributed it to
changes in reactivity of the LBS I domain (kringle IV10) induced by
phospholipolysis. In conclusion, the extensive modification of Lp[a] caused by
PLA2 digestion had no significant influence on the reactivity of LBS II, which is
the domain involved in the binding of apo[a] to fibrinogen and apoB-100. These
results also suggest that phospholipids do not play an important role in these
interactions.
PMID- 10191283
TI - Serum sterols during stanol ester feeding in a mildly hypercholesterolemic
population.
AB - We investigated the changes of cholesterol and non-cholesterol sterol metabolism
during plant stanol ester margarine feeding in 153 hypercholesterolemic subjects.
Rapeseed oil (canola oil) margarine without (n = 51) and with (n = 102) stanol (2
or 3 g/day) ester was used for 1 year. Serum sterols were analyzed with gas
liquid chromatography. The latter showed a small increase in sitostanol peak
during stanol ester margarine eating. Cholestanol, campesterol, and sitosterol
proportions to cholesterol were significantly reduced by 5-39% (P < 0.05 or less
for all) by stanol esters; the higher their baseline proportions the higher were
their reductions. The precursor sterol proportions were significantly increased
by 10- 46%, and their high baseline levels predicted low reduction of serum
cholesterol. The decrease of the scheduled stanol dose from 3 to 2 g/day after 6
month feeding increased serum cholesterol by 5% (P < 0. 001) and serum plant
sterol proportions by 8-13% (P < 0.001), but had no consistent effect on
precursor sterols. In twelve subjects, the 12-month level of LDL cholesterol
exceeded that of baseline; the non-cholesterol sterol proportions suggested that
stimulated synthesis with relatively weak absorption inhibition contributed to
the non-responsiveness of these subjects. In conclusion, plant stanol ester
feeding lowers serum cholesterol in about 88% of subjects, decreases the non
cholesterol sterols that reflect cholesterol absorption, increases the sterols
that reflect cholesterol synthesis, but also slightly increases serum plant
stanols. Low synthesis and high absorption efficiency of cholesterol results in
the greatest benefit from stanol ester consumption.
PMID- 10191284
TI - Stereochemistry of the alpha-oxidation of 3-methyl-branched fatty acids in rat
liver.
AB - The stereochemistry of the alpha-oxidation of 3-methyl-branched fatty acids was
studied in rat liver. R- and S-3-methylhexadecanoic acid were equally well alpha
oxidized in intact hepatocytes and homogenates. Subcellular fractionation studies
showed that alpha-oxidation of both isomers is confined to peroxisomes.
Dehydrogenation of 2-methylpentadecanal, the end-product of the peroxisomal alpha
oxidation of 3-methylhexadecanoic acid, to 2-methylpentadecanoic acid, followed
by derivatization with R-1-phenylethylamine and subsequent separation of the
stereoisomers by gas chromatography, revealed that the configuration of the
methyl-branch is preserved throughout the whole alpha-oxidation process.
Metabolism and formation of the 2-hydroxy-3-methylhexadecanoyl-CoA intermediate
were also investigated. Separation of the methyl esters of the four isomers of 2
hydroxy-3-methylhexadecanoic acid was achieved by gas chromatography after
derivatization of the hydroxy group with R-2-methoxy-2
trifluoromethylphenylacetic acid chloride and the absolute configuration of the
four isomers was determined. Although purified peroxisomes are capable of
metabolizing all four isomers of 2-hydroxy-3-methylhexadecanoyl-CoA, they can
only form the (2S,3R) and the (2R,3S) isomers. Our experiments exclude the
racemization of the 3-methyl branch during the alpha-oxidation process. The
configuration of the 3-methyl branch does not influence the rate of alpha
oxidation, but determines the side of the 2-hydroxylation, hence the
configuration of the 2-hydroxy-3-methylacyl-CoA intermediates formed during the
process.
PMID- 10191285
TI - Expression and intracellular processing of the 58 kDa sterol carrier protein-2/3
oxoacyl-CoA thiolase in transfected mouse L-cell fibroblasts.
AB - Although the sterol carrier protein 2 (SCP-2) gene encodes for two proteins,
almost nothing is known of the function and potential processing of the larger
transcript corresponding to the 58 kDa sterol carrier protein-2/3-oxoacyl-CoA
thiolase (SCP-x), in intact cells. L-cell fibroblasts transfected with cDNA
encoding for the 58 kDa SCP-x protein had a 4.5-fold increase in SCP-x mRNA
transcript levels. Western blot analysis showed SCP-x protein expression reached
0.011% of total protein, representing a 4.1-fold increase over basal levels.
Surprisingly, the 13.2 kDa SCP-2 protein also increased 2-fold in the transfected
cells. This was consistent with part of the 58 kDa SCP-x being proteolytically
processed to 13.2 kDa SCP-2 as there was no evidence of an mRNA transcript
corresponding to a 13.2/15.2 kDa gene product in the transfected L-cell clones.
Confocal immunofluorescence microscopy of transfected L-cells showed that SCP
x/SCP-2 co-localized in highest concentration with catalase in peroxisomes, but
significant amounts appeared extra-peroxisomal. Overexpression of SCP-x
significantly altered cholesterol uptake and metabolism. Uptake of exogenous
[3H]cholesterol and total cholesterol mass were increased 1.9- and 1.4-fold,
respectively, in SCP-x expressors. Although cholesterol ester mass was unaltered,
incorporation of exogenous [3H]cholesterol and [3H]oleic acid into cholesteryl
esters increased 2.3- and 2.5-fold, respectively. These results from intact cells
suggest the 13.2 kDa SCP-2 can arise from the larger SCP-2 gene product and
indicate a role for the 58 kDa SCP-x protein in cholesterol uptake and
intracellular cycling.
PMID- 10191286
TI - Mutational analysis of apolipoprotein B mRNA editing enzyme (APOBEC1). structure
function relationships of RNA editing and dimerization.
AB - APOBEC1 is the catalytic subunit of an enzyme complex that mediates
apolipoprotein (apo) B mRNA editing. It dimerizes in vitro and requires
complementation factor(s) for its editing activity. We have performed a
systematic analysis of the structure-functional relationship of APOBEC1 by
targeted mutagenesis of various sequence motifs within the protein. Using in
vitro RNA editing assay, we found that basic amino acid clusters at the amino
terminal region R15R16R17 and R33K34, are essential for apoB mRNA editing.
Mutation of R15R16R17 to K15K16K17 and mutation of R33K34 simultaneously to
A33A34 almost completely abolished in vitro editing activity. The carboxy
terminal region of APOBEC1 contains a leucine-rich motif. Deletion analysis of
this region indicates that residues 181 to 210 are important for in vitro apoB
mRNA editing. Single amino acid substitutions demonstrate that L182, I185, and
L189 are important residues required for normal editing function. Furthermore,
the double mutant P190A/P191A also lost >90% of editing activity which suggests
that a beta turn in this region of the molecule may be essential for proper
functioning of APOBEC1. It was suggested that dimerization of APOBEC1 creates an
active structure for deamination of apoB mRNA. When we examined the dimerization
potential of truncated APOBEC1s using both amino and carboxy termini deletion
mutants, we found that amino-terminal deletions up to residue A117 did not impair
dimerization activity whereas carboxy-terminal deletions showed diminished
dimerization. The systematic and extensive mutagenesis experiments in this study
provide information on the role of various sequence motifs identified in APOBEC1
in enzyme catalysis and dimerization.
PMID- 10191287
TI - Characterization of remnant-like particles isolated by immunoaffinity gel from
the plasma of type III and type IV hyperlipoproteinemic patients.
AB - Previous studies have investigated the potential atherogenicity and
thrombogenicity of triglyceride-rich lipoprotein (TRL) remnants by isolating them
from plasma within a remnant-like particle (RLP) fraction, using an
immunoaffinity gel containing specific anti-apoB-100 and anti-apoA-I antibodies.
In order to characterize lipoproteins in this RLP fraction and to determine to
what extent their composition varies from one individual to another, we have used
automated gel filtration chromatography to determine the size heterogeneity of
RLP isolated from normolipidemic control subjects (n = 8), and from type III (n =
6) and type IV (n = 9) hyperlipoproteinemic patients, who by selection had
similarly elevated levels of plasma triglyceride (406 +/- 43 and 397 +/- 35
mg/dl, respectively). Plasma RLP triglyceride, cholesterol, apoB, apoC-III, and
apoE concentrations were elevated 2- to 6-fold (P < 0. 05) in
hyperlipoproteinemic patients compared to controls. RLP fractions of type III
patients were enriched in cholesterol and apoE compared to those of type IV
patients, and RLP of type IV patients were enriched in triglyceride and apoC-III
relative to those of normolipidemic subjects. In normolipidemic subjects, the
majority of RLP had a size similar to LDL or HDL. The RLP of hyperlipoproteinemic
patients were, however, larger and were similar in size to TRL, or were
intermediate in size (i.e., ISL) between that of TRL and LDL. Compared to
controls, ISL in the RLP fraction of type III patients were enriched in apoE
relative to apoC-III, whereas in type IV patients they were enriched in apoC-III
relative to apoE. These results demonstrate that: 1) RLP are heterogeneous in
size and composition in both normolipidemic and hypertriglyceridemic subjects,
and 2) the apoE and apoC-III composition of RLP is different in type III compared
to type IV hyperlipoproteinemic patients.
PMID- 10191288
TI - Expression of serum amyloid A protein in the absence of the acute phase response
does not reduce HDL cholesterol or apoA-I levels in human apoA-I transgenic mice.
AB - Plasma concentrations of high density lipoprotein (HDL) cholesterol and its major
apolipoprotein (apo)A-I are significantly decreased in inflammatory states.
Plasma levels of the serum amyloid A (SAA) protein increase markedly during the
acute phase response and are elevated in many chronic inflammatory states.
Because SAA is associated with HDL and has been shown to be capable of displacing
apoA-I from HDL in vitro, it is believed that expression of SAA is the primary
cause of the reduced HDL cholesterol and apoA-I in inflammatory states. In order
to directly test this hypothesis, we constructed recombinant adenoviruses
expressing the murine SAA and human SAA1 genes (the major acute phase SAA
proteins in both species). These recombinant adenoviruses were injected
intravenously into wild-type and human apoA-I transgenic mice and the effects of
SAA expression on HDL cholesterol and apoA-I were compared with mice injected
with a control adenovirus. Plasma levels of SAA were comparable to those seen in
the acute phase response in mice and humans. However, despite high plasma levels
of murine or human SAA, no significant changes in HDL cholesterol or apoA-I
levels were observed. SAA was found associated with HDL but did not specifically
alter the cholesterol or human apoA-I distribution among lipoproteins. In
summary, high plasma levels of SAA in the absence of a generalized acute phase
response did not result in reduction of HDL cholesterol or apoA-I in mice,
suggesting that there are components of the acute phase response other than SAA
expression that may directly influence HDL metabolism.
PMID- 10191289
TI - Phospholipid transfer protein (PLTP) causes proteolytic cleavage of
apolipoprotein A-I.
AB - Plasma phospholipid transfer protein (PLTP) is a factor that plays an important
role in HDL metabolism. In this study we present data suggesting that PLTP has an
inherent protease activity. After incubation of HDL3 in the presence of purified
plasma PLTP, the d < 1.25 g/ml particles (fusion particles) contained intact 28.2
kDa apoA-I while the d > 1.25 g/ml fraction (apoA-I-PL complexes) contained, in
addition to intact apoA-I, a cleaved 23 kDa form of apoA-I. Purified apoA-I was
also cleaved by PLTP and produced a similar 23 kDa apoA-I fragment. The cleavage
of apoA-I increased as a function of incubation time and the amount of PLTP
added. The process displayed typically an 8-10 h lag or induction period, after
which the cleavage proceeded in a time-dependent manner. This lag-phase was
necessary for the development of the cleavage activity during incubation at 37
degrees C. The specific apoA-I cleavage activity of different PLTP preparations
varied between 0.4-0.8 microg apoA-I degraded/h per 1000 nmol per h of PLTP
activity. The 23 kDa apoA-I fragment reacted with monoclonal antibodies specific
for the N-terminal part of apoA-I, indicating that the apoA-I cleavage occurred
in the C-terminal portion. The apoA-I cleavage products were further
characterized by mass spectrometry. The 23 kDa fragment yielded a mass of 22.924
kDa, demonstrating that the cleavage occurs in the C-terminal portion of apoA-I
between amino acid residues 196 (alanine) and 197 (threonine). The intact apoA-I
and the 23 kDa fragment revealed identical N-terminal amino acid sequences. The
cleavage of apoA-I could be inhibited with APMSF and chymostatin, suggesting that
it is due to a serine esterase-type of proteolytic activity. Recombinant PLTP
produced in CHO cells or using the baculovirus-insect cell system caused an apoA
I cleavage pattern identical to that obtained with plasma PLTP. The present
results raise the question of whether PLTP-mediated proteolytic cleavage of apoA
I might affect plasma HDL metabolism by generating a novel kinetic compartment of
apoA-I with an increased turnover rate.
PMID- 10191290
TI - Urinary excretion of 2,7, 8-trimethyl-2-(beta-carboxyethyl)-6-hydroxychroman is a
major route of elimination of gamma-tocopherol in humans.
AB - Little is known of the post-absorptive, metabolic fate of gamma-tocopherol, the
major form of vitamin E in North American diets. The objective of this study was
to determine the extent of urinary excretion of 2,7, 8-trimethyl-2-(beta
carboxyethyl)-6-hydroxychroman (gamma-CEHC), a recently identified metabolite of
gamma-tocopherol. A method for measurement of urinary gamma-CEHC was developed,
using gas chromatography-mass spectrometry (GC-MS) with a deuterated internal
standard, 2,7,8-trimethyl-2-(beta-carboxyethyl)-(3, 4-2H2)-6-hydroxychroman (d2
gamma-CEHC). This standard was synthesized by dehydrogenation of 6-acetyl-gamma
CEHC followed by deuteration of the resulting 3,4-double bond. The use of d2
gamma-CEHC resulted in accurate determinations of the concentration of d0-gamma
CEHC in human urine. Urine samples containing added d2-gamma-CEHC were treated
with beta-glucuronidase, extracted with an organic solvent, and analyzed by GC
MS. Analysis of 24-h urine pools from healthy subjects revealed gamma-CEHC
concentrations, normalized against creatinine, ranging from 2.5 to 31.5
micromol/g creatinine, or a total of 4.6 to 29.8 micromol per day. These results
correspond to 2-12 mg gamma-tocopherol excreted daily as gamma-CEHC in the urine.
Given an estimated mean intake of gamma-tocopherol of 20 mg/day, catabolism of
gamma-tocopherol to gamma-CEHC, followed by glucuronide conjugation and urinary
excretion, is a major pathway for elimination of gamma-tocopherol in humans.
PMID- 10191291
TI - Characterization of phosphomevalonate kinase: chromosomal localization,
regulation, and subcellular targeting.
AB - Phosphomevalonate kinase catalyzes the conversion of mevalonate-5-phosphate to
mevalonate-5-diphosphate and was originally believed to be a cytosolic enzyme. In
this study we have localized the phosphomevalonate kinase gene to chromosome 1p13
1q22-23 and present a genomic map indicating that the gene spans more than 8.4 kb
in the human genome. Furthermore, we show that message levels and enzyme activity
of rat liver phosphomevalonate kinase are regulated in response to dietary sterol
levels and that this regulation is coordinate with 3-hydroxy-3-methylglutaryl
coenzyme A reductase, the rate-limiting enzyme of cholesterol biosynthesis. In
addition, we demonstrate that phosphomevalonate kinase is a peroxisomal protein
which requires the C-terminal peroxisomal targeting signal, Ser-Arg-Leu, for
localization to the organelle.
PMID- 10191292
TI - Apolipoprotein E knock-out mice are highly susceptible to endotoxemia and
Klebsiella pneumoniae infection.
AB - Lipoproteins are able to neutralize bacterial lipopolysaccharide (LPS) and
thereby inhibit the proinflammatory cytokine response. In a previous study, we
demonstrated that hypercholesterolemic low density lipoprotein receptor knock-out
(LDLr-/-) mice are protected against lethal endotoxemia and gram-negative
infection. In the present study we investigated the susceptibility of
apolipoprotein E knock-out mice (apoE-/-) to LPS and to Klebsiella pneumoniae.
These mice have increased plasma lipoprotein concentrations in the very low
density lipoprotein (VLDL)-sized fraction. Despite 8 -fold higher plasma
cholesterol levels compared to controls, and in contrast to LDLr-/- mice, apoE-/-
mice were significantly more susceptible to endotoxemia and to K. pneumoniae
infection. Circulating TNFalpha concentrations after intravenously injected LPS
were 4 - to 5-fold higher in apoE-/- mice, whereas IL-1alpha, IL-1beta, and IL-6
did not differ. This TNF response was not due to an increased cytokine production
capacity of cells from apoE-/- mice, as ex vivo cytokine production in response
to LPS did not differ between apoE-/- and control mice. The LPS-neutralizing
capacity of apoE-/- plasma was significantly less than that of controls. Most
likely, the absence of apoE itself in the knock-out mice explains the failure to
neutralize LPS, despite the very high cholesterol concentrations.
PMID- 10191293
TI - Selective modification of apoB-100 in the oxidation of low density lipoproteins
by myeloperoxidase in vitro.
AB - Oxidative modification of LDL may be important in the initiation and/or
progression of atherosclerosis, but the precise mechanisms through which low
density lipoprotein (LDL) is oxidized are unknown. Recently, evidence for the
existence of HOCl-oxidized LDL in human atherosclerotic lesions has been
reported, and myeloperoxidase (MPO), which is thought to act through production
of HOCl, has been identified in human atherosclerotic lesions. In the present
report we describe the formation of 2,4-dinitrophenylhydrazine (DNPH)-reactive
modifications in the apolipoprotein (apo) by exposure of LDL to myeloperoxidase
in vitro. In contrast with the complex mixture of peptides from oxidation of LDL
with reagent HOCl, oxidation with MPO in vitro produced a major tryptic peptide
showing absorbance at 365 nm. This peptide was isolated and characterized as
VELEVPQL(*C)SFILK..., corresponding to amino acid residues 53-66...on apoB-100.
Mass spectrometric analyses of two tryptic peptides from oxidation of LDL by HOCl
indicated formation of the corresponding methionine sulfoxide (M=O), cysteinyl
azo (*C), RS -N= N-DNP, derivatives of EEL(*C)T(M=O)FIR and LNDLNS
VLV(M=O)PTFHVPFTDLQVPS(*C)K, which suggest oxidation to the corresponding
sulfinic acids (RSO2H) by HOCl. The present results demonstrate that DNPH
reactive modifications other than aldehydes and ketones can be formed in the
oxidation of proteins and illustrate how characterization of specific products of
protein oxidation can be useful in assessing the relative contributions of
different and unexpected mechanisms to the oxidation of LDL and other target
substrates. The data also suggest a direct interaction of the LDL particle with
the active site on myeloperoxidase and indicate that effects of the protein
microenvironment can greatly influence product formation and stability.
PMID- 10191294
TI - 13-(S)-hydroxyoctadecadienoic acid (13-HODE) incorporation and conversion to
novel products by endothelial cells.
AB - 13(S)-Hydroxy-[12,13-3H]octadecadienoic acid (13-HODE), a linoleic acid oxidation
product that has vasoactive properties, was rapidly taken up by bovine aortic
endothelial cells. Most of the 13-HODE was incorporated into phosphatidylcholine,
and 80% was present in the sn -2 position. The amount of 13-HODE retained in the
cells gradually decreased, and radiolabeled metabolites with shorter reverse
phase high-performance liquid chromatography retention times (RT) than 13-HODE
accumulated in the extracellular fluid. The three major metabolites were
identified by gas chromatography combined with mass spectrometry as 11
hydroxyhexadecadienoic acid (11-OH-16:2), 9-hydroxytetradecadienoic acid (9-OH
14:2), and 7-hydroxydodecadienoic acid (7-OH-12:2). Most of the radioactivity
contained in the cell lipids remained as 13-HODE. However, some 11-OH-16:2 and
several unidentified products with longer RT than 13-HODE were detected in the
cell lipids. Normal human skin fibroblasts also converted 13-HODE to the three
major chain-shortened metabolites, but Zellweger syndrome fibroblasts produced
only a very small amount of 11-OH-16:2. Therefore, the chain-shortened products
probably are formed primarily by peroxisomal beta-oxidation. These findings
suggest that peroxisomal beta-oxidation may constitute a mechanism for the
inactivation and removal of 13-HODE from the vascular wall. Because this is a
gradual process, some 13-HODE that is initially incorporated remains in
endothelial phospholipids, especially phosphatidylcholine. This may be the cause
of some of the functional perturbations produced by 13-HODE in the vascular wall.
PMID- 10191295
TI - Phytanic acid is ligand and transcriptional activator of murine liver fatty acid
binding protein.
AB - Branched-chain phytanic acid is metabolized in liver peroxisomes. Sterol carrier
protein 2/sterol carrier protein x (SCP2/SCPx) knockout mice, which develop a
phenotype with a deficiency in phytanic acid degradation, accumulate dramatically
high concentrations of this fatty acid in serum (Seedorf at al. 1998. Genes Dev.
12: 1189-1201) and liver. Concomitantly, a 6.9-fold induction of liver fatty acid
binding protein (L-FABP) expression is observed in comparison to wild-type
animals fed standard chow, possibly mediated by the peroxisome proliferator
activated receptor alpha (PPARalpha). Cytosolic transport of phytanic acid to
either peroxisomal membranes or to the nucleus for activation of PPARalpha may be
mediated by L-FABP, which gives rise to the question whether phytanic acid is a
transactivator of this protein. Here we show first that phytanic acid binds to
recombinant L-FABP with high affinity. Then the increase of the in vivo phytanic
acid concentration by phytol feeding to mice results in a 4-fold induction of L
FABP expression in liver, which is in the order of that attained with
bezafibrate, a known peroxisome proliferator. Finally to test in vitro whether
this induction is conferred by phytanic acid, we cotransfected HepG2 cells with
an expression plasmid for murine PPARalpha and a CAT-reporter gene with 176 bp of
the murine L-FABP promoter, containing the peroxisome proliferator responsive
element (PPRE). After incubation with phytanic acid, we observed a 3.2-fold
induction of CAT expression. These findings, both in vivo and in vitro,
demonstrate that phytanic acid is a transcriptional activator of L-FABP
expression and that this effect is mediated via PPARalpha.
PMID- 10191296
TI - Purification and properties of a cholesteryl ester hydrolase from rat liver
microsomes.
AB - This report describes a purification procedure for a cholesteryl ester hydrolase
(CEH) from female rat liver microsomes, and some structural, immunological,
kinetic, and regulatory properties of the enzyme that distinguish the microsomal
CEH from other hepatic cholesteryl ester-splitting enzymes. CEH was purified 12.4
fold from reisolated microsomes using sequential solubilization by sonication,
polyethylene glycol precipitation, fractionation with hydroxyapatite, anion
exchange chromatography, and chromatography on hydroxyapatite, with an overall
yield of 3.2%. CEH activity was purified 141-fold over nonspecific esterase
activity and 56-fold over triacylglycerol lipase activity. In sharp contrast with
most esterases and lipases, CEH did not bind to concanavalin A-Sepharose and
heparin-Sepharose. After polyacrylamide gel electrophoresis, the purified enzyme
exhibited two silver-stained bands, but only the protein electroeluted from the
low mobility band had CEH activity. Affinity-purified polyclonal antibodies
raised to electroeluted CEH inhibited 90% of the activity of liver microsomal CEH
and reacted with a 106 kDa protein band on Western blot analysis. This 106 kDa
CEH contains a unique N-terminal amino acid sequence. The purified enzyme had
optimal activity at pH 6 and no taurocholate requirements, and was inhibited by
the serine active site inhibitor phenylmethylsulfonyl fluoride and by free
sulfhydryl specific reagents. It hydrolyzed cholesteryl oleate much more
efficiently than trioleine, and hydrolytic activity with p-nitrophenyl acetate
was higher than with p-nitrophenyl butyrate. These results indicate that rat
liver microsomes contain a bile salt-independent catalytic protein that is
relatively specific for cholesteryl ester hydrolysis.
PMID- 10191297
TI - Antilithiasic effect of beta-cyclodextrin in LPN hamster: comparison with
cholestyramine.
AB - Beta-Cyclodextrin (BCD), a cyclic oligosaccharide that binds cholesterol and bile
acids in vitro, has been previously shown to be an effective plasma cholesterol
lowering agent in hamsters and domestic pigs. This study examined the effects of
BCD as compared with cholestyramine on cholesterol and bile acid metabolism in
the LPN hamster model model for cholesterol gallstones. The incidence of
cholesterol gallstones was 65% in LPN hamsters fed the lithogenic diet, but
decreased linearly with increasing amounts of BCD in the diet to be nil at a dose
of 10% BCD. In gallbladder bile, cholesterol, phospholipid and chenodeoxycholate
concentrations, hydrophobic and lithogenic indices were all significantly
decreased by 10% BCD. Increases in bile acid synthesis (+110%), sterol 27
hydroxylase activity (+106%), and biliary cholate secretion (+140%) were also
observed, whereas the biliary secretion of chenodeoxycholate decreased (-43%).
The fecal output of chenodeoxycholate and cholate (plus derivatives) was
increased by +147 and +64%, respectively, suggesting that BCD reduced the
chenodeoxycholate intestinal absorption preferentially. Dietary cholestyramine
decreased biliary bile acid concentration and secretion, but dramatically
increased the fecal excretion of chenodeoxycholate and cholate plus their
derivatives (+328 and +1940%, respectively). In contrast to BCD, the resin
increased the lithogenic index in bile, induced black gallstones in 34% of
hamsters, and stimulated markedly the activities of HMG-CoA reductase (+670%),
sterol 27-hydroxylase (+310%), and cholesterol 7alpha-hydroxylase (+390%). Thus,
beta-cyclodextrin (BCD) prevented cholesterol gallstone formation by decreasing
specifically the reabsorption of chenodeoxycholate, stimulating its biosynthesis
and favoring its fecal elimination. BCD had a milder effect on lipid metabolism
than cholestyramine and does not predispose animals to black gallstones as
cholestyramine does in this animal model.
PMID- 10191298
TI - Lipoprotein lipase activity is decreased in a large cohort of patients with
coronary artery disease and is associated with changes in lipids and
lipoproteins.
AB - Lipoprotein lipase (LPL) is crucial in the hydrolysis of triglycerides (TG) in TG
rich lipoproteins in the formation of HDL particles. As both these lipoproteins
play an important role in the pathogenesis of atherosclerotic vascular disease,
we sought to assess the relationship between post-heparin LPL (PH-LPL) activity
and lipids and lipoproteins in a large, well-defined cohort of Dutch males with
coronary artery disease (CAD). These subjects were drawn from the REGRESS study,
totaled 730 in number and were evaluated against 75 healthy, normolipidemic male
controls. Fasting mean PH-LPL activity in the CAD subjects was 108 46 mU/ml,
compared to 138 44 mU/ml in controls (P < 0.0001). When these patients were
divided into activity quartiles, those in the lowest versus the highest quartile
had higher levels of TG (P < 0.001), VLDLc and VLDL-TG (P = 0.001). Conversely,
levels of TC, LDL, and HDLc were lower in these patients (P = 0.001, P = 0.02,
and P = 0.001, respectively). Also, in this cohort PH-LPL relationships with
lipids and lipoproteins were not altered by apoE genotypes. The frequency of
common mutations in the LPL gene associated with partial LPL deficiency (N291S
and D9N carriers) in the lowest quartile for LPL activity was more than double
the frequency in the highest quartile (12.0% vs. 5.0%; P = 0.006). By contrast,
the frequency of the S447X LPL variant rose from 11.5% in the lowest to 18.3% (P
= 0.006) in the highest quartile. This study, in a large cohort of CAD patients,
has shown that PH-LPL activity is decreased (22%; P = 0.001) when compared to
controls; that the D9N and N291S, and S447X LPL variants are genetic
determinants, respectively, in CAD patients of low and high LPL PH-LPL
activities; and that PH-LPL activity is strongly associated with changes in
lipids and lipoproteins.
PMID- 10191299
TI - Antipeptide antibodies reveal interrelationships of MBP 200 and MBP 235: unique
apoB-specific receptors for triglyceride-rich lipoproteins on human monocyte
macrophages.
AB - Two human monocyte-macrophage (HMM) membrane binding proteins, (MBP) 200 and 235,
are receptor candidates that bind to the apolipoprotein (apo)B-48 domain in
triglyceride-rich lipoproteins for uptake independent of apoE. Microsequence
analysis of the purified reduced MBP 200R characterized tryptic peptides of MBP
200R. A synthetic peptide mimicking a unique, unambiguous 10-residue sequence
(AEGLMVTGGR) induced antipeptide antibodies that specifically recognized MBP 200,
235 and 200R, in 1- and 2-dimensional analyses, indicating 1) the ligand binding
protein was sequenced and 2) MBP 200 and 235 yielded MBP 200R upon reduction.
These antibodies identified the MBPs in human blood-borne, THP-1, U937 MMs, and
endothelial cells (EC) but not in human fibroblasts or Chinese hamster ovary
(CHO) cells. Fluorescence activated cell sorting (FACS) analysis located the MBPs
on the MM surface as necessary for receptor function. The 10-residue, unambiguous
MBP 200-derived sequence is unique, with no matches in extant protein databases.
Antipeptide antibodies bind to the MBPs in reticuloendothelial cells that have
this receptor activity, but not to proteins in cells that lack this receptor
activity. These studies provide the first direct protein sequence and
immunochemical data that a new, unique apoB receptor for triglyceride-rich
lipoproteins exists in human monocytes, macrophages, and endothelial cells.
PMID- 10191300
TI - Peptide model of a highly conserved, N-terminal domain of apolipoprotein E is
able to modulate lipoprotein binding to a member of the class A scavenger
receptor family.
AB - Apolipoprotein E plays a critical role in plasma lipoprotein clearance. Peptide
models of a highly conserved, N-terminal domain of this protein have been shown
to increase the binding of low density lipoprotein (LDL) to fibroblast cell
surfaces independently of the low density lipoprotein receptor. Here we provide
data to show that these peptides not only increase the binding of LDL, but also
of high density lipoprotein, though not acetylated LDL. We also have data
suggesting that this novel activity is mediated, at least in part, by a member of
the scavenger receptor family, SR-AI. Furthermore, we show that this activity is
also prominent in macrophages, a cell relevant to atherogenesis. In addition,
this current paper provides evidence suggesting that this complex binding
activity is initiated by a peptide-receptor interaction, and that our peptides
are able to induce activity at physiologically relevant concentrations. This
study provides evidence for a possible novel receptor interaction and further
anti-atherogenic properties of apolipoprotein E and raises the possibility of a
therapeutic potential of our peptide models.
PMID- 10191301
TI - New methods for determining the enantiomeric purity of erythro -sphingosine.
AB - The enantiomeric purity of erythro -sphingosine samples can be determined simply,
reliably, and accurately from 1H or 19F nuclear magnetic resonance spectra of the
alpha-methoxy-alpha-(trifluoromethyl)phenylacetate (MTPA) derivative. As little
as 0.1% of the minor enantiomer could be observed in a 1-mg sample, and detection
limits of 1% and 5% were estimated for samples of 100 microg and 10 microg. The
two threo -sphingosine enantiomers and four dihydrosphingosine stereoisomers were
also differentiated by this technique, which served as an effective method for
assessing the purity of sphingosine and dihydrosphingosine samples. Enantiomeric
and diastereomeric purities could also be determined by normal-phase high
performance liquid chromatographic analysis of the MTPA derivatives.
PMID- 10191302
TI - Regulation of intracellular chloride by cotransporters in developing lateral
superior olive neurons.
AB - The regulatory mechanisms of intracellular Cl- concentration ([Cl-]i) were
investigated in the lateral superior olive (LSO) neurons of various developmental
stages by taking advantage of gramicidin perforated patch recording mode, which
enables neuronal [Cl-]i measurement. Responses to glycine changed from
depolarization to hyperpolarization during the second week after birth, resulting
from [Cl-]i decrease. Furosemide equally altered the [Cl-]i of both immature and
mature LSO neurons, indicating substantial contributions of furosemide-sensitive
intracellular Cl- regulators; i.e., K+-Cl- cotransporter (KCC) and Na+-K+-Cl-
cotransporter (NKCC), throughout this early development. Increase of
extracellular K+ concentration and replacement of intracellular K+ with Cs+
resulted in [Cl-]i elevation at postnatal days 13-15 (P13-P15), but not at P0-P2,
indicating that the mechanism of neuronal Cl- extrusion is sensitive to both
furosemide and K+-gradient and poorly developed in immature LSO neurons. In
addition, removal of extracellular Na+ decreased [Cl-]i at P0-P2, suggesting the
existence of extracellular Na+-dependent and furosemide-sensitive Cl-
accumulation in immature LSO neurons. These data show clearly that developmental
changes of Cl- cotransporters alter [Cl-]i and are responsible for the switch
from the neonatal Cl- efflux to the mature Cl- influx in LSO neurons. Such
maturational changes in Cl- cotransporters might have the important functional
roles for glycinergic and GABAergic synaptic transmission and the broader
implications for LSO and auditory development.
PMID- 10191303
TI - Specific alteration of spontaneous GABAergic inhibition in cerebellar purkinje
cells in mice lacking the potassium channel Kv1. 1.
AB - In the cerebellum, the basket cell innervation on Purkinje cells provides a major
GABAergic inhibitory control of the single efferent output from the cerebellum.
The Shaker-type K channel Kv1.1 is localized at the axon arborization preceding
the terminal of the basket cells and is therefore a potential candidate for
regulating the GABAergic inhibition. In this study, we directly assess this role
of Kv1.1 by electrophysiological analysis of Kv1.1 null mutant mice. Whole-cell
patch-clamp recordings of spontaneous IPSCs (sIPSCs) were made from Purkinje
cells in thin cerebellar slices from postnatal day (P)10-15 Kv1.1-null mutants
using wild-type littermates as controls. The null mutation confers a very
specific change in the sIPSC: the frequency increases about twofold, without
accompanying changes in the mean and variance of its amplitude distribution. The
frequency and amplitude of the miniature IPSCs (mIPSCs) are unaffected.
Spontaneous firing rate of the basket cells is unaltered. Evoked IPSC does not
show multiple activity in the mutants. Motor skills tests show that Kv1.1 null
mice display a compromised ability to maintain balance on a thin stationary rod.
We conclude that the Kv1.1 null mutation results in a persistent elevation of the
tonic inhibitory tone on the cerebellum Purkinje cell efferent and that this is
not fully compensated for by residual Shaker-type channels. We further suggest
that the increase in inhibitory tone in the mutants might underlie the behavioral
deficits. At the cellular level, we propose that Kv1.1 deletion enhances
excitability of the basket cells by selectively enhancing the likelihood of
action potential propagation past axonal branch points.
PMID- 10191304
TI - Synchronized paroxysmal activity in the developing thalamocortical network
mediated by corticothalamic projections and "silent" synapses.
AB - In mouse thalamocortical slices in vitro, the potassium channel blocker 4-AP and
GABAA receptor antagonist bicuculline together induced spontaneous prolonged
depolarizations in layer VI neurons from postnatal day 2 (P2), in ventroposterior
nucleus neurons (VP) from P7, and in reticular nucleus neurons (RTN) from P8.
Dual whole-cell recordings revealed that prolonged bursts were synchronized in
layer VI, VP, and RTN. Bursts were present in cortex isolated from thalamus, but
not in thalamus isolated from cortex, indicating that bursts originated in cortex
and propagated to thalamus. Prolonged bursts were synchronized in layer VI when
vertical cuts extended from pia mater through layers IV or V, but were no longer
synchronized when cuts extended through layer VI and white matter. In voltage
clamp recordings before P10, burst conductance of all three neuronal populations
was dominated by the NMDA receptor-mediated conductance, and therefore synapses
were "silent". In cortex and RTN, after P10, bursts were associated with strong
AMPA/kainate receptor-mediated conductances, and synapses had become
"functional"; silent synapses persisted in a large proportion of VP cells after
P10. Before P9, the NMDA receptor antagonist APV or the non-NMDA receptor
antagonist CNQX blocked the prolonged bursts. After P9, CNQX continued to block
the prolonged bursts, but APV merely shortened their duration. Thus, NMDA
receptor-based silent synapses are essential for paroxysmal corticothalamic
activity during early postnatal development, and connections between layer VI
neurons are sufficient for horizontal cortical synchronization.
PMID- 10191305
TI - Slices have more synapses than perfusion-fixed hippocampus from both young and
mature rats.
AB - Hippocampal slices have long been used to investigate properties of synaptic
transmission and plasticity. Here, for the first time, synapses in slices have
been compared quantitatively with synapses occurring in perfusion-fixed
hippocampus, which is presumed to represent the natural in vivo state. Relative
to perfusion-fixed hippocampus, a remarkable 40-50% increase in spine number
occurs in adult hippocampal slices, and a 90% increase occurs in slices from
postnatal day 21 rats. Serial EM shows that all of the dendritic spines have
normal synapses with presynaptic and postsynaptic elements; however, not all
spine types are affected uniformly. Stubby and mushroom spines increase in the
adult slices, and thin, mushroom, and branched spines increase in the immature
slices. More axonal boutons with multiple synapses occur in the slices,
suggesting that the new synapses form on preexisting axonal boutons. The increase
in spine and synapse number is evident within a couple of hours after preparing
the slices. Once the initial spine induction has occurred, no further change
occurs for up to 13 hr in vitro, the longest time investigated. Thus, the spine
increase is occurring during a period when there is little or no synaptic
activity during the first hour, and the subsequent stabilization in spine synapse
numbers is occurring after synaptic activity returns in the slice. These findings
suggest that spines form in response to the loss of synaptic activity when slices
are removed from the rest of the brain and during the subsequent 1 hr recovery
period.
PMID- 10191306
TI - Nicotinic receptor activation excites distinct subtypes of interneurons in the
rat hippocampus.
AB - We examined the function of nicotinic acetylcholine receptors (nAChRs) in
interneurons of area CA1 of the rat hippocampus. CA1 interneurons could be
classified into three categories based on nicotinic responses. The first class
was depolarized by alpha7 nAChRs, found in all layers of CA1 and as a group, had
axonal projections to all neuropil layers of CA1. The second class had both fast
alpha7 and slow non-alpha7 nAChR depolarizing responses, was localized primarily
to the stratum oriens, and had axonal projections to the stratum lacunosum
moleculare. The third group had no nicotinic response. This group was found in or
near the stratum pyramidale and had axonal projections almost exclusively within
and around this layer. Low concentrations (500 nM) of nicotine desensitized fast
and slow nAChR responses. These findings demonstrate that there are distinct
subsets of interneurons with regard to nicotinic receptor expression and with
predictable morphological properties that suggest potential cellular actions for
nicotinic receptor activation in normal CNS function and during nicotine abuse.
PMID- 10191307
TI - Role of intrinsic conductances underlying responses to transients in octopus
cells of the cochlear nucleus.
AB - Recognition of acoustic patterns in natural sounds depends on the transmission of
temporal information. Octopus cells of the mammalian ventral cochlear nucleus
form a pathway that encodes the timing of firing of groups of auditory nerve
fibers with exceptional precision. Whole-cell patch recordings from octopus cells
were used to examine how the brevity and precision of firing are shaped by
intrinsic conductances. Octopus cells responded to steps of current with small,
rapid voltage changes. Input resistances and membrane time constants averaged 2.4
MOmega and 210 microseconds, respectively (n = 15). As a result of the low input
resistances of octopus cells, action potential initiation required currents of at
least 2 nA for their generation and never occurred repetitively. Backpropagated
action potentials recorded at the soma were small (10-30 mV), brief (0.24-0.54
msec), and tetrodotoxin-sensitive. The low input resistance arose in part from an
inwardly rectifying mixed cationic conductance blocked by cesium and potassium
conductances blocked by 4-aminopyridine (4-AP). Conductances blocked by 4-AP also
contributed to the repolarization of the action potentials and suppressed the
generation of calcium spikes. In the face of the high membrane conductance of
octopus cells, sodium and calcium conductances amplified depolarizations produced
by intracellular current injection over a time course similar to that of EPSPs.
We suggest that this transient amplification works in concert with the shunting
influence of potassium and mixed cationic conductances to enhance the encoding of
the onset of synchronous auditory nerve fiber activity.
PMID- 10191308
TI - Functional analysis of a mouse brain Elk-type K+ channel.
AB - Members of the Ether a go-go (Eag) K+ channel subfamilies Eag, Erg, and Elk are
widely expressed in the nervous system, but their neural functions in vivo remain
largely unknown. The biophysical properties of channels from the Eag and Erg
subfamilies have been described, and based on their characteristic features and
expression patterns, Erg channels have been associated with native currents in
the heart. Little is known about the properties of channels from the Elk
subfamily. We have identified a mouse gene, Melk2, that encodes a predicted
polypeptide with 48% amino acid identity to Drosophila Elk but only 40 and 36%
identity with mouse Erg (Merg) and Eag (Meag), respectively. Melk2 RNA appears to
be expressed at high levels only in brain tissue. Functional expression of Melk2
in Xenopus oocytes reveals large, transient peaks of current at the onset of
depolarization. Like Meag currents, Melk2 currents activate relatively quickly,
but they lack the nonsuperimposable Cole-Moore shift characteristic of the Eag
subfamily. Melk2 currents are insensitive to E-4031, a class III antiarrhythmic
compound that blocks the Human Ether-a-go-go-Related Gene (HERG) channel and its
counterpart in native tissues, IKr. Melk2 channels exhibit inward rectification
because of a fast C-type inactivation mechanism, but the slower rate of
inactivation and the faster rate of activation results in less inward
rectification than that observed in HERG channels. This characterization of Melk
currents should aid in identification of native counterparts to the Elk subfamily
of channels in the nervous system.
PMID- 10191309
TI - A 29 kDa intracellular chloride channel p64H1 is associated with large dense-core
vesicles in rat hippocampal neurons.
AB - A novel class of intracellular chloride channels, the p64 family, has been found
on several types of vesicles. These channels, acting in concert with the
electrogenic proton pump, regulate the pH of the vesicle interior, which is
critical for vesicular function. Here we describe the molecular cloning of p64H1,
a p64 homolog, from both human and cow. Northern blot analysis showed that p64H1
is expressed abundantly in brain and retina, whereas the other members of this
family (e.g., p64 and NCC27) are expressed only at low levels in these tissues.
Immunohistochemical analysis of p64H1 in rat brain, using an affinity-purified
antibody, revealed a high level of expression in the limbic system-the
hippocampal formation, the amygdala, the hypothalamus, and the septum.
Immunoelectron microscopic analysis of p64H1 in hippocampal neurons demonstrated
a striking association between p64H1 and large dense-core vesicles (LDCVs) and
microtubules. In contrast, very low p64H1 labeling was found in perikarya or
associated with small synaptic vesicles (SSVs) in axonal profiles. Immunoblot
analysis confirmed that p64H1 is colocalized with heavy membrane fractions
containing LDCVs rather than the fractions containing SSVs. These results suggest
that p64H1-mediated Cl- permeability may be involved in the maintenance of low
internal pH in LDCVs and in the maturation of LDCVs and the biogenesis of
functional neuropeptides.
PMID- 10191310
TI - Effects of phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 4
phosphate on a Na+-gated nonselective cation channel.
AB - Olfactory receptor neurons in the lobster express a nonselective cation channel
that is activated by intracellular Na+ and carries a substantial part of the
depolarizing receptor current. Here, we show that phosphatidylinositol 4,5
bisphosphate [PI(4,5)P2] and phosphatidylinositol 4-phosphate [PI(4)P] applied to
the intracellular face of cell-free patches activate the channel in the absence
of Na+ and that antibodies against the respective phospholipids irreversibly
inhibit the evoked activity. Further, we show that applying PI(4,5)P2 or PI(4)P
in the presence of Na+ decreases the concentration of Na+ required to activate
the channel from an EC50 of 74 to 22 mM for PI(4,5)P2 and to 29 mM for PI(4)P,
respectively. Na+-gated channel activity was irreversibly inhibited by monoclonal
antibodies against PI(4,5)P2 and PI(4)P in patches never exposed to exogenous
phosphatidylinositols, suggesting that endogenous inositol phospholipids are
required for the activation of the channel by intracellular Na+. Our findings
suggest that PI(4,5)P2 and/or PI(4)P may serve as intracellular signaling
molecules in these primary sensory neurons and provide a general mechanism to
explain how the sensitivity of Na+-gated channels to Na+ could be much greater in
intact cells than in excised membrane patches.
PMID- 10191311
TI - The metabotropic receptor mGluR6 may signal through G(o), but not
phosphodiesterase, in retinal bipolar cells.
AB - Bipolar cells are retinal interneurons that receive synaptic input from
photoreceptors. Glutamate, the photoreceptor transmitter, hyperpolarizes On
bipolar cells by closing nonselective cation channels, an effect mediated by the
metabotropic receptor mGluR6. Previous studies of mGluR6 transduction have
suggested that the receptor couples to a phosphodiesterase (PDE) that
preferentially hydrolyzes cGMP, and that cGMP directly gates the nonselective
cation channel. This hypothesis was tested by dialyzing On bipolar cells with
nonhydrolyzable analogs of cGMP. Whole-cell recordings were obtained from On
bipolar cells in slices of larval tiger salamander retina. Surprisingly, On
bipolar cells dialyzed with 8-(4-chlorophenylthio)-cyclic GMP (8-pCPT-cGMP), or 8
bromo-cyclic GMP (8-Br-cGMP) responded normally to glutamate or L-2-amino-4
phosphonobutyrate (L-APB). Response amplitudes and kinetics were not
significantly altered compared with cells dialyzed with cGMP alone. Comparable
results were obtained with the PDE inhibitor 3-isobutyl-1-methyl-xanthine (IBMX)
or with 8-pCPT-cGMP and IBMX together, indicating that PDE is not required for
mGluR6 signal transduction. Addition of the G-protein subunit G(o)alpha to the
pipette solution suppressed the cation current and occluded the glutamate
response, whereas dialysis with G(i)alpha or with transducin Gbetagamma had no
significant effect on either the cation current or the response. Dialysis of an
antibody directed against G(o)alpha also reduced the glutamate response,
indicating a functional role for endogenous G(o)alpha. These results indicate
that mGluR6 may signal through G(o), rather than a transducin-like G-protein.
PMID- 10191312
TI - Calcitonin gene-related peptide rapidly downregulates nicotinic receptor function
and slowly raises intracellular Ca2+ in rat chromaffin cells in vitro.
AB - Although calcitonin gene-related peptide (CGRP) modulates muscle-type nicotinic
acetylcholine receptors (nAChRs) via intracellular second messenger-mediated
phosphorylation, the action of this peptide on neuronal-type nAChRs remains
unknown. Using neuronal nAChRs of rat chromaffin cells in vitro we studied the
effect of CGRP, which is physiologically present in adrenal medulla, on membrane
currents and [Ca2+]i transients elicited by nicotine. Our main novel observation
was that CGRP (either bath-applied or focally applied for a few seconds or even
co-applied with nicotine for a few milliseconds) selectively and rapidly blocked
nAChRs (a phenomenon unlikely caused by intracellular messengers in view of its
speed) without affecting GABA receptors. The inhibitory effect of CGRP was
independent of [Ca2+]i or membrane potential and not accompanied by baseline
current changes. Like the competitive antagonist N,N,N-trimethyl-1-(4-trans
stilbenoxy)-2-propilammonium, CGRP induced a rightward, parallel shift of the
nicotine dose-response curve; during co-application of these blockers the
nicotine dose-ratio value was the sum of the values obtained with each antagonist
alone. The block by CGRP was insensitive to the receptor antagonist hCGRP8-37 but
mimicked by CGRP1-7. Persistent application of CGRP slowly increased [Ca2+]i, a
phenomenon independent from external Ca2+, thus implying Ca2+ release from
internal stores, and suppressed by hCGRP8-37. CGRP1-7 had no significant effect
on [Ca2+]i. We propose that the 1-7 amino acid sequence of CGRP was responsible
for the direct, rapid block of nAChRs, whereas the full-length peptide molecule
was necessary for the delayed rise in internal Ca2+ potentially able to trigger
phosphorylation-dependent modulation of nicotinic receptor function.
PMID- 10191313
TI - AMPA receptor activates a G-protein that suppresses a cGMP-gated current.
AB - The AMPA receptor, ubiquitous in brain, is termed "ionotropic" because it gates
an ion channel directly. We found that an AMPA receptor can also modulate a G
protein to gate an ion channel indirectly. Glutamate applied to a retinal
ganglion cell briefly suppresses the inward current through a cGMP-gated channel.
AMPA and kainate also suppress the current, an effect that is blocked both by
their general antagonist CNQX and also by the relatively specific AMPA receptor
antagonist GYKI-52466. Neither NMDA nor agonists of metabotropic glutamate
receptors are effective. The AMPA-induced suppression of the cGMP-gated current
is blocked when the patch pipette includes GDP-beta-S, whereas the suppression is
irreversible when the pipette contains GTP-gamma-S. This suggests a G-protein
mediator, and, consistent with this, pertussis toxin blocks the current
suppression. Nitric oxide (NO) donors induce the current suppressed by AMPA, and
phosphodiesterase inhibitors prevent the suppression. Apparently, the AMPA
receptor can exhibit a "metabotropic" activity that allows it to antagonize
excitation evoked by NO.
PMID- 10191314
TI - Single-channel properties of synaptic and extrasynaptic GABAA receptors suggest
differential targeting of receptor subtypes.
AB - Many neurons express a multiplicity of GABAA receptor subunit isoforms. Despite
having only a single source of inhibitory input, the cerebellar granule cell
displays, at various stages of development, more than 10 different GABAA subunit
types. This subunit diversity would be expected to result in significant receptor
heterogeneity, yet the functional consequences of such heterogeneity remain
poorly understood. Here we have used single-channel properties to characterize
GABAA receptor types in the synaptic and extrasynaptic membrane of granule cells.
In the presence of high concentrations of GABA, which induced receptor
desensitization, extrasynaptic receptors in outside-out patches from the soma
entered long-lived closed states interrupted by infrequent clusters of openings.
Each cluster of openings, which is assumed to result from the repeated activation
of a single channel, was to one of three main conductance states (28, 17, or 12
pS), the relative frequency of which differed between patches. Such behavior
indicates the presence of at least three different receptor types. This
heterogeneity was not replicated by individual recombinant receptors
(alpha1beta2gamma2S or alpha1beta3gamma2S), which gave rise to clusters of a
single type only. By contrast, the conductance of synaptic receptors, determined
by fluctuation analysis of the synaptic current or direct resolution of channel
events, was remarkably uniform and similar to the highest conductance value seen
in extrasynaptic patches. These results suggest that granule cells express
multiple GABAA receptor types, but only those with a high conductance, most
likely containing a gamma subunit, are activated at the synapse.
PMID- 10191315
TI - Overexpression of alpha-internexin causes abnormal neurofilamentous accumulations
and motor coordination deficits in transgenic mice.
AB - alpha-Internexin is the first neuronal intermediate filament (IF) protein
expressed in postmitotic neurons of the developing nervous system. In the adult,
its expression is restricted to mature neurons in the CNS. To study the potential
role of alpha-internexin in neurodegeneration, we have generated transgenic mice
that overexpress rat alpha-internexin. The total levels of alpha-internexin
expressed in the hemizygous and homozygous transgenic mice were approximately 2
and approximately 3 times the normal level, respectively. Overexpression of alpha
internexin resulted in the formation of cerebellar torpedoes as early as 1 month
of age. These torpedoes are abnormal swellings of Purkinje cell axons that are
usually seen in neurodegenerative diseases involving the cerebellum. EM studies
showed accumulations of high levels of IFs and abnormal organelles in the
torpedoes and soma of Purkinje cells, as well as in the large pyramidal neurons
of the neocortex and in the ventral anterior and posteromedial nuclei of the
thalamus. Behavioral tests demonstrate that these mice have a deficit in motor
coordination as early as 3 months of age, consistent with the morphological
neuronal changes. Our data further demonstrate that the neurofilamentous
inclusions also lead to progressive loss of neurons in the aged transgenic mice.
The motor coordination deficit and the loss of neurons are transgene dosage
dependent. These data yield direct evidence that high levels of misaccumulated
neuronal IFs lead to neuronal dysfunction, progressive neurodegeneration, and
ultimate loss of neurons. Moreover, the degrees of neuronal dysfunction and
degeneration are proportional to the levels of misaccumulated neuronal IFs.
PMID- 10191316
TI - Cannabinoids and neuroprotection in global and focal cerebral ischemia and in
neuronal cultures.
AB - Marijuana and related drugs (cannabinoids) have been proposed as treatments for a
widening spectrum of medical disorders. R(+)-[2, 3-dihydro-5-methyl-3
[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1, 4-benzoxazin-yl]-(1
naphthalenyl)methanone mesylate (R(+)-WIN 55212-2), a synthetic cannabinoid
agonist, decreased hippocampal neuronal loss after transient global cerebral
ischemia and reduced infarct volume after permanent focal cerebral ischemia
induced by middle cerebral artery occlusion in rats. The less active enantiomer
S(-)-WIN 55212-3 was ineffective, and the protective effect of R(+)-WIN 55212-2
was blocked by the specific central cannabinoid (CB1) cannabinoid receptor
antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2, 4-dichlorophenyl)-4-methyl
1H-pyrazole-3-carboxamide-hydrochloride. R(+)-WIN 55212-2 also protected cultured
cerebral cortical neurons from in vitro hypoxia and glucose deprivation, but in
contrast to the receptor-mediated neuroprotection observed in vivo, this in vitro
effect was not stereoselective and was insensitive to CB1 and CB2 receptor
antagonists. Cannabinoids may have therapeutic potential in disorders resulting
from cerebral ischemia, including stroke, and may protect neurons from injury
through a variety of mechanisms.
PMID- 10191317
TI - Contribution of p53-dependent caspase activation to neuronal cell death declines
with neuronal maturation.
AB - Caspases play a pivotal role in neuronal cell death during development and after
trophic factor withdrawal. However, the mechanisms regulating caspase activity
and the role played by caspase activation in response to neuronal injury is
poorly understood. The tumor suppressor gene p53 has been implicated in the loss
of neuronal viability caused by excitotoxic and DNA damaging agents. In the
present study we determined if p53-mediated neuronal cell death required caspase
activation. DNA damage increased caspase activity in both cultured embryonic
telencephalic and postnatal cortical neurons in a p53-dependent manner. Caspase
inhibitors protected embryonic telencephalic neurons, but not postnatal cortical
neurons, from DNA damage-induced cell death as measured by direct cell counting
and annexin V staining. In marked contrast to the caspase inhibitors, an
inhibitor of the DNA repair enzyme, poly(ADP-ribose) polymerase, conferred
significant protection from genotoxic and excitotoxic cell death on postnatal
cortical neurons but had no effect on embryonic neurons. Glutamate-mediated
excitotoxicity in postnatal neurons was not associated with measurable changes in
caspase activity, consistent with the failure of caspase inhibitors to prevent
cell death under these conditions. Moreover, adenovirus-mediated overexpression
of p53 killed embryonic and postnatal neurons without activating caspases. Thus,
p53-mediated neuronal cell death may occur via both caspase-dependent and caspase
independent pathways. These results demonstrate that p53 is required for caspase
activation in response to some forms of neuronal injury. However, the relative
importance of caspase activation in neurons depends on the developmental status
of the cell and the specific nature of the death stimulus.
PMID- 10191318
TI - Cholinergic and GABAergic inputs drive patterned spontaneous motoneuron activity
before target contact.
AB - Patterned spontaneous electrical activity has been demonstrated in a number of
developing neural circuits and has been proposed to play a role in refining
connectivity once axons reach their targets. Using an isolated spinal cord
preparation, we have found that chick lumbosacral motor axons exhibit highly
regular bursts of activity from embryonic day 4 (E4) (stage 24-25), shortly after
they exit the spinal cord and while still en route toward their target muscles.
Similar bursts could be evoked by stimulating descending pathways at cervical or
thoracic levels. Unlike older embryonic cord circuits, the major excitatory
transmitter driving activity was not glutamate but acetylcholine, acting
primarily though nicotinic non-alpha7 receptors. The circuit driving bursting was
surprisingly robust and plastic, because bursting was only transiently blocked by
cholinergic antagonists, and following recovery, was now driven by GABAergic
inputs. Permanent blockade of spontaneous activity was only achieved by a
combination of cholinergic antagonists and bicuculline, a GABAA antagonist. The
early occurrence of patterned motor activity suggests that it could be playing a
role in either peripheral pathfinding or spinal cord circuit formation and
maturation. Finally, the characteristic differences in burst parameters already
evident between different motoneuron pools at E4 would require that the
combination of transcription factors responsible for specifying pool identity to
have acted even earlier.
PMID- 10191319
TI - Glutamate receptor expression regulates quantal size and quantal content at the
Drosophila neuromuscular junction.
AB - At the Drosophila glutamatergic neuromuscular junction, the postsynaptic cell can
regulate synaptic strength by both changing its sensitivity to neurotransmitter
and generating a retrograde signal that regulates presynaptic transmitter
release. To investigate the molecular mechanisms underlying these forms of
plasticity, we have undertaken a genetic analysis of two postsynaptic glutamate
receptors that are expressed at this synapse. Deletion of both genes results in
embryonic lethality that can be rescued by transgenic expression of either
receptor. Although these receptors are redundant for viability, they have
important differences. By transgenically rescuing the double mutant, we have
investigated the relationship of receptor gene dosage and composition to synaptic
function. We find that the receptor subunit composition regulates quantal size,
Argiotoxin sensitivity, and receptor desensitization kinetics. Finally, we show
that the activity of the receptor can regulate the retrograde signal functioning
at this synapse. Thus, the diversity of receptors expressed at this synapse
provides the cell with mechanisms for generating synaptic plasticity.
PMID- 10191320
TI - A changing pattern of brain-derived neurotrophic factor expression correlates
with the rearrangement of fibers during cochlear development of rats and mice.
AB - The reorganization of specific neuronal connections is a typical feature of the
developing nervous system. It is assumed that the refinement of connections in
sensory systems requires spontaneous activity before the onset of cochlear
function and selective sensory experience during the ensuing period. The
mechanism of refinement through sensory experience is currently postulated as
being based on the selective reinforcement of active projections by
neurotrophins. We studied a presumed role of neurotrophins for rearrangement of
afferent and efferent fibers before the onset of sensory function in the
precisely innervated auditory end organ, the cochlea. We observed a
spatiotemporal change in the localization of brain-derived neurotrophic factor
(BDNF) protein and mRNA, which correlated with the reorganization of fibers.
Thus, BDNF decreased in target hair cells during fiber retraction and was
subsequently upregulated in neurons, target hair cells, and adjacent supporting
cells concomitant with the formation of new synaptic contacts. Analysis of the
innervation pattern in BDNF gene-deleted mice by immunohistochemistry and
confocal microscopy revealed a failure in the rearrangement of fibers and a BDNF
dependency of distinct neuronal projections that reorganize in control animals.
Our data suggest that, before the onset of auditory function, a spatiotemporal
change in BDNF expression in sensory, epithelial, and neuronal cells may guide
the initial steps of refinement of the innervation pattern.
PMID- 10191321
TI - Oligodendrocyte apoptosis mediated by caspase activation.
AB - Treatment with NGF causes long-term cultures of oligodendrocytes to die via a yet
undefined mechanism mediated by the p75 neurotrophin receptor. The p75 receptor
belongs to the TNF receptor superfamily of molecules, which includes Fas and p55
TNF receptors. The Fas and TNF receptors use adaptor molecules to recruit and
activate caspase-8 to the receptor. Using a combination of immunohistochemical
and Western blotting assays, we have examined caspase activity during NGF-induced
apoptosis. Interestingly, although caspase-1 [interleukin-1beta-converting enzyme
(ICE)], caspase-2, caspase-3, and caspase-8 were expressed in oligodendrocytes,
only caspase-1, -2, and -3 were activated after NGF treatment, whereas caspase-8
was not. These data suggest that the mechanism of apoptosis by NGF through the
p75 receptor is different from TNF and Fas-mediated killing. gamma Radiation of
oligodendrocytes also activated a similar subset of caspases as NGF, indicating
that NGF-induced oligodendrocyte apoptosis uses a similar cell death execution
mechanism as injury models. This consolidates a potential role of the p75
neurotrophin receptor during stress and inflammatory conditions.
PMID- 10191322
TI - Mandarin and English single word processing studied with functional magnetic
resonance imaging.
AB - The cortical organization of language in bilinguals remains disputed. We studied
24 right-handed fluent bilinguals: 15 exposed to both Mandarin and English before
the age of 6 years; and nine exposed to Mandarin in early childhood but English
only after the age of 12 years. Blood oxygen level-dependent contrast functional
magnetic resonance imaging was performed while subjects performed cued word
generation in each language. Fixation was the control task. In both languages,
activations were present in the prefrontal, temporal, and parietal regions, and
the supplementary motor area. Activations in the prefrontal region were compared
by (1) locating peak activations and (2) counting the number of voxels that
exceeded a statistical threshold. Although there were differences in the
magnitude of activation between the pair of languages, no subject showed
significant differences in peak-location or hemispheric asymmetry of activations
in the prefrontal language areas. Early and late bilinguals showed a similar
pattern of overlapping activations. There are no significant differences in the
cortical areas activated for both Mandarin and English at the single word level,
irrespective of age of acquisition of either language.
PMID- 10191323
TI - Differential c-Fos expression in cholinergic, monoaminergic, and GABAergic cell
groups of the pontomesencephalic tegmentum after paradoxical sleep deprivation
and recovery.
AB - Multiple lines of evidence indicate that neurons within the pontomesencephalic
tegmentum are critically involved in the generation of paradoxical sleep (PS).
From single-unit recording studies, evidence suggests that unidentified but
"possibly" cholinergic tegmental neurons discharge at higher rates during PS than
during slow wave sleep or even waking and would thus play an active role, whereas
"presumed" monoaminergic neurons cease firing during PS and would thus play a
permissive role in PS generation. In the present study performed on rats, c-Fos
immunostaining was used as a reflection of neuronal activity and combined with
immunostaining for choline acetyltransferase (ChAT), serotonin (Ser), tyrosine
hydroxylase (TH), or glutamic acid decarboxylase (GAD) for immunohistochemical
identification of active neurons during PS recovery ( approximately 28% of
recording time) as compared with PS deprivation (0%) and PS control
(approximately 15%) conditions. With PS recovery, there was a significant
increase in ChAT+/c-Fos+ cells, a significant decrease in Ser+/c-Fos+ and TH+/c
Fos+ cells, and a significant increase in GAD+/c-Fos+ cells. Across conditions,
the percent PS was correlated positively with tegmental cholinergic c-Fos+ cells,
negatively with raphe serotonergic and locus coeruleus noradrenergic c-Fos+
cells, and positively with codistributed and neighboring GABAergic c-Fos+ cells.
These results support the hypothesis that cholinergic neurons are active, whereas
monoaminergic neurons are inactive during PS. They moreover indicate that
GABAergic neurons are active during PS and could thus be responsible for
inhibiting neighboring monoaminergic neurons that may be essential in the
generation of PS.
PMID- 10191324
TI - Spatiotemporal patterns of activity in an intact mammalian network with single
cell resolution: optical studies of nicotinic activity in an enteric plexus.
AB - Multiple Site Optical Recording of Transmembrane Voltage (MSORTV) has been used
to measure, continuously and simultaneously, the spontaneous electrical activity
from all of the neurons in individual ganglia or up to five interconnected
ganglia of the submucous plexus of the guinea pig small intestine. These are the
first optical recordings of electrical activity with single-cell resolution from
a mammalian nervous system. They are used to investigate the effects of acute and
chronic application of nicotine on the firing patterns of this neural network
containing important cholinergic components. After washout of acutely applied
nicotine, the firing rates of selected neurons were dramatically elevated. These
results suggest that nAChRs that reversibly desensitize after exposure to
nicotine may be responsible for the enhancement of activity that is observed
after a brief application of this agonist. In addition, immunostaining with
monoclonal antibodies was used to localize alpha3/alpha5, alpha7, and beta2 nAChR
subunits, and the results demonstrate the prevalence of alpha3/alpha5. It is this
alpha3-containing nAChR subtype that probably accounts for most of the excess
activity elicited by nicotine application.
PMID- 10191325
TI - Selective color constancy deficits after circumscribed unilateral brain lesions.
AB - The color of an object, when part of a complex scene, is determined not only by
its spectral reflectance but also by the colors of all other objects in the scene
(von Helmholtz, 1886; Ives, 1912; Land, 1959). By taking global color information
into account, the visual system is able to maintain constancy of the color
appearance of the object, despite large variations in the light incident on the
retina arising from changes in the spectral content of the illuminating light
(Hurlbert, 1998; Maloney, 1999). The neural basis of this color constancy is,
however, poorly understood. Although there seems to be a prominent role for
retinal, cone-specific adaptation mechanisms (von Kries, 1902; Poppel, 1986;
Foster and Nascimento, 1994), the contribution of cortical mechanisms to color
constancy is still unclear (Land et al., 1983; D'Zmura and Lennie, 1986). We
examined the color perception of 27 patients with defined unilateral lesions
mainly located in the parieto-temporo-occipital and fronto-parieto-temporal
cortex. With a battery of clinical and specially designed color vision tests we
tried to detect and differentiate between possible deficits in central color
processing. Our results show that color constancy can be selectively impaired
after circumscribed unilateral lesions in parieto-temporal cortex of the left or
right hemisphere. Five of 27 patients exhibited significant deficits in a color
constancy task, but all of the 5 performed well in color discrimination or higher
level visual tasks, such as the association of colors with familiar objects.
These results indicate that the computations underlying color constancy are
mediated by specialized cortical circuitry, which is independent of the neural
substrate for color discrimination and for assigning colors to objects.
PMID- 10191326
TI - Glossopharyngeal nerve transection eliminates quinine-stimulated fos-like
immunoreactivity in the nucleus of the solitary tract: implications for a
functional topography of gustatory nerve input in rats.
AB - The relationship between specific gustatory nerve activity and central patterns
of taste-evoked neuronal activation is poorly understood. To address this issue
within the first central synaptic relay in the gustatory system, we examined the
distribution of neurons in the nucleus of the solitary tract (NST) activated by
the intraoral infusion of quinine using Fos immunohistochemistry in rats with
bilateral transection of the chorda tympani (CTX), bilateral transection of the
glossopharyngeal nerve (GLX), or combined neurotomy (DBLX). Compared with
nonstimulated and water-stimulated controls, quinine evoked significantly more
Fos-like-immunoreactive (FLI) neurons across the rostrocaudal extent of the
gustatory NST (gNST), especially within its dorsomedial portion (subfield 5).
Although the somatosensory aspects of fluid stimulation contributed to the
observed increase in FLI neurons, the elevated number and spatial distribution of
FLI neurons in response to quinine were remarkably distinguishable from those in
response to water. GLX and DBLX produced a dramatic attenuation of quinine-evoked
FLI neurons and a shift in their spatial distribution such that their number and
pattern were indiscernable from those observed in water-stimulated controls.
Although CTX had no effect on the number of quinine-evoked FLI neurons within
subfield 5 at intermediate levels of the gNST, it produced intermediate effects
elsewhere; yet, the spatial distribution of the quinine-evoked FLI neurons was
not altered by CTX. These findings suggest that the GL provides input to all FLI
neurons responsive to quinine, however, some degree of convergence with CT input
apparently occurs in this subpopulation of neurons. Although the role of these
FLI neurons in taste-guided behavioral responses to quinine remains speculative,
their possible function in oromotor reflex control is considered.
PMID- 10191327
TI - A theory of geometric constraints on neural activity for natural three
dimensional movement.
AB - Although the orientation of an arm in space or the static view of an object may
be represented by a population of neurons in complex ways, how these variables
change with movement often follows simple linear rules, reflecting the underlying
geometric constraints in the physical world. A theoretical analysis is presented
for how such constraints affect the average firing rates of sensory and motor
neurons during natural movements with low degrees of freedom, such as a limb
movement and rigid object motion. When applied to nonrigid reaching arm
movements, the linear theory accounts for cosine directional tuning with linear
speed modulation, predicts a curl-free spatial distribution of preferred
directions, and also explains why the instantaneous motion of the hand can be
recovered from the neural population activity. For three-dimensional motion of a
rigid object, the theory predicts that, to a first approximation, the response of
a sensory neuron should have a preferred translational direction and a preferred
rotation axis in space, both with cosine tuning functions modulated
multiplicatively by speed and angular speed, respectively. Some known tuning
properties of motion-sensitive neurons follow as special cases. Acceleration
tuning and nonlinear speed modulation are considered in an extension of the
linear theory. This general approach provides a principled method to derive
mechanism-insensitive neuronal properties by exploiting the inherently low
dimensionality of natural movements.
PMID- 10191328
TI - Axons from anteroventral cochlear nucleus that terminate in medial superior olive
of cat: observations related to delay lines.
AB - The differences in path length of axons from the anteroventral cochlear nuclei
(AVCN) to the medial superior olive (MSO) are thought to provide the anatomical
substrate for the computation of interaural time differences (ITD). We made small
injections of biotinylated dextran into the AVCN that produced intracellular-like
filling of axons. This permitted three-dimensional reconstructions of individual
axons and measurements of axonal length to individual terminals in MSO. Some
axons that innervated the contralateral MSO had collaterals with lengths that
were graded in the rostrocaudal direction with shorter collaterals innervating
more rostral parts of MSO and longer collaterals innervating more caudal parts of
MSO. These could innervate all or part of the length of the MSO. Other axons had
restricted terminal fields comparable to the size of a single dendritic tree in
the MSO. In the ipsilateral MSO, some axons had a reverse, but less steep,
gradient in axonal length with greater axonal length associated with more rostral
locations; others had restricted terminal fields. Thus, the computation of ITDs
is based on gradients of axonal length in both the contralateral and ipsilateral
MSO, and these gradients may account for a large part of the range of ITDs
encoded by the MSO. Other factors may be involved in the computation of ITDs to
compensate for differences between axons.
PMID- 10191329
TI - Neurotrophin modulation of the monosynaptic reflex after peripheral nerve
transection.
AB - The effects of neurotrophin-3 (NT-3) and NT-4/5 on the function of axotomized
group Ia afferents and motoneurons comprising the monosynaptic reflex pathway
were investigated. The axotomized medial gastrocnemius (MG) nerve was provided
with NT-3 or NT-4/5 for 8-35 d via an osmotic minipump attached to its central
end at the time of axotomy. After this treatment, monosynaptic EPSPs were
recorded intracellularly from MG or lateral gastrocnemius soleus (LGS)
motoneurons in response to stimulation of the heteronymous nerve under
pentobarbital anesthesia. Controls were preparations with axotomized nerves
treated directly with vehicle; other axotomized controls were administered
subcutaneous NT-3. Direct NT-3 administration (60 microgram/d) not only prevented
the decline in EPSP amplitude from axotomized afferents (stimulate MG, record
LGS) observed in axotomy controls but, after 5 weeks, led to EPSPs larger than
those from intact afferents. These central changes were paralleled by recovery of
group I afferent conduction velocity. Removal of NT-3 4-5 weeks after beginning
treatment resulted in a decline of conduction velocity and EPSP amplitude within
1 week to values characteristic of axotomy. The increased synaptic efficacy after
NT-3 treatment was associated with enhanced connectivity of single afferents to
motoneurons. NT-4/5 induced modest recovery in group I afferent conduction
velocity but not of the EPSPs they elicited. NT-3 or NT-4/5 had no effect on the
properties of treated motoneurons or their monosynaptic EPSPs. We conclude that
NT-3, and to a limited extent NT-4/5, promotes recovery of axotomized group Ia
afferents but not axotomized motoneurons or the synapses on them.
PMID- 10191330
TI - Hypothalamic hypocretin (orexin): robust innervation of the spinal cord.
AB - Hypocretin (orexin) is synthesized by neurons in the lateral hypothalamus and has
been reported to increase food intake and regulate the neuroendocrine system. In
the present paper, long descending axonal projections that contain hypocretin
were found that innervate all levels of the spinal cord from cervical to sacral
segments, as studied in mouse, rat, and human spinal cord and not previously
described. High densities of axonal innervation are found in regions of the
spinal cord related to modulation of sensation and pain, notably in the marginal
zone (lamina 1). Innervation of the intermediolateral column and lamina 10 as
well as strong innervation of the caudal region of the sacral cord suggest that
hypocretin may participate in the regulation of both the sympathetic and
parasympathetic parts of the autonomic nervous system. Double-labeling
experiments in mice combining retrograde transport of diamidino yellow after
spinal cord injections and immunocytochemistry support the concept that
hypocretin-immunoreactive fibers in the cord originate from the neurons in the
lateral hypothalamus. Digital-imaging physiological studies with fura-2 detected
a rise in intracellular calcium in response to hypocretin in cultured rat spinal
cord neurons, indicating that spinal cord neurons express hypocretin-responsive
receptors. A greater number of cervical cord neurons responded to hypocretin than
another hypothalamo-spinal neuropeptide, oxytocin. These data suggest that in
addition to possible roles in feeding and endocrine regulation, the descending
hypocretin fiber system may play a role in modulation of sensory input,
particularly in regions of the cord related to pain perception and autonomic
tone.
PMID- 10191331
TI - Sympathetic neuronal oscillators are capable of dynamic synchronization.
AB - In this paper we show that the discharges of sympathetic neurons innervating an
identified peripheral target are driven by multiple oscillators that undergo
dynamic synchronization when an entraining force, central respiratory drive
(CRD), is increased. Activity was recorded from postganglionic sympathetic
neurons (PGNs) innervating the caudal ventral artery of the rat tail: (1) at the
population level from the ventral collector nerve (VCN); and (2) from pairs of
single PGNs recorded simultaneously using a focal recording technique.
Autospectral analysis of VCN activity revealed a more prominent rhythmical
component in the presence of CRD than in its absence, suggesting that (1)
multiple oscillators drive the discharges of PGNs and (2) these oscillators can
be entrained and therefore synchronized by CRD. This interpretation was supported
by analysis of the firing behavior of PGN pairs. Autocorrelation and cross
correlation analysis showed that pairs were not synchronized in the absence of
CRD but showed significant synchronization when CRD was enhanced. Time-evolving
spectral analysis and raster plots demonstrated that the temporal stability of
PGN-to-PGN and CRD-to-PGN interactions at a given level of CRD were also dynamic
in nature, with stable constant phase relationships predominating as CRD was
increased. This is the first reported example of dynamic synchronization in
populations of single postganglionic sympathetic neurons, and we suggest that, as
in sensory processing and motor control, temporal pattern coding may also be an
important feature of neuronal discharges in sympathetic pathways.
PMID- 10191332
TI - Long-term effects of transcranial magnetic stimulation on hippocampal reactivity
to afferent stimulation.
AB - Transcranial magnetic stimulation (TMS) has become a promising treatment of
affective disorders in humans, yet the neuronal basis of its long-lasting effects
in the brain is still unknown. We studied acute and lasting effects of TMS on
reactivity of the rat hippocampus to stimulation of the perforant path.
Application of TMS to the brain of the anesthetized rat caused a dose-dependent
transient increase in population spike (PS) response of the dentate gyrus to
perforant path stimulation. In addition, TMS caused a marked decrease in
inhibition and an increase in paired-pulse potentiation of reactivity to
stimulation of the perforant path. Also, TMS suppressed the ability of
fenfluramine (FFA), a serotonin releaser, to potentiate PS response to perforant
path stimulation. Chronic TMS did not affect single population spikes but caused
an increase in paired-pulse potentiation, which was still evident 3 weeks after
the last of seven daily TMS treatments. After chronic TMS, FFA was ineffective in
enhancing reactivity to perforant path stimulation, probably because it lost the
ability to release serotonin. In addition, the beta adrenergic receptor agonist
isoproterenol, which caused an increase in PS in the control rats, failed to do
so in the TMS-treated rats. These results indicate that TMS produces a long-term
reduction in efficacy of central modulatory systems.
PMID- 10191333
TI - Key role of 5-HT1B receptors in the regulation of paradoxical sleep as evidenced
in 5-HT1B knock-out mice.
AB - The involvement of 5-HT1B receptors in the regulation of vigilance states was
assessed by investigating the spontaneous sleep-waking cycles and the effects of
5-HT receptor ligands on sleep in knock-out (5-HT1B-/-) mice that do not express
this receptor type. Both 5-HT1B-/- and wild-type 129/Sv mice exhibited a clear
cut diurnal sleep-wakefulness rhythm, but knock-out animals were characterized by
higher amounts of paradoxical sleep and lower amounts of slow-wave sleep during
the light phase and by a lack of paradoxical sleep rebound after deprivation. In
wild-type mice, the 5-HT1B agonists CP 94253 (1-10 mg/kg, i.p.) and RU 24969
(0.25-2.0 mg/kg, i.p.) induced a dose-dependent reduction of paradoxical sleep
during the 2-6 hr after injection, whereas the 5-HT1B/1D antagonist GR 127935
(0.1-1.0 mg/kg, i.p.) enhanced paradoxical sleep. In addition, pretreatment with
GR 127935, but not with the 5-HT1A antagonist WAY 100635, prevented the effects
of both 5-HT1B agonists. In contrast, none of the 5-HT1B receptor ligands, at the
same doses as those used in wild-type mice, had any effect on sleep in 5-HT1B-/-
mutants. Finally, the 5-HT1A agonist 8-OH-DPAT (0.2-1.2 mg/kg, s.c.) induced in
both strains a reduction in the amount of paradoxical sleep. Altogether, these
data indicate that 5-HT1B receptors participate in the regulation of paradoxical
sleep in the mouse.
PMID- 10191334
TI - Hormonal regulation of glutamate receptor gene expression in the anteroventral
periventricular nucleus of the hypothalamus.
AB - Glutamate plays an important role in mediating the positive feedback effects of
ovarian steroids on gonadotropin secretion, and the preoptic region of the
hypothalamus is a likely site of action of glutamate. The anteroventral
periventricular nucleus (AVPV) of the preoptic region is an essential part of
neural pathways mediating hormonal feedback on gonadotropin secretion, and it
appears to provide direct inputs to gonadotropin releasing hormone (GnRH)
containing neurons. Immunohistochemistry and in situ hybridization were used in
this study to define the distribution and hormonal regulation of glutamate
receptor subtypes in the AVPV of juvenile female rats. Neurons that express the
NMDAR1 receptor subtype are abundant in the AVPV, as are cells that express AMPA
receptor subtypes (GluR1, GluR2, and GluR3 but not GluR4), and the AVPV appears
to contain a dense plexus of NMDAR1-immunoreactive presynaptic terminals.
However, AVPV neurons do not seem to express detectable levels of kainate
receptor (GluR5, GluR6, and GluR7) or metabotropic receptor (mGluR1-6) subtypes.
Treatment of ovariectomized juvenile rats with estradiol induced expression of
GluR1 mRNA but did not alter levels of GluR2 or GluR3 mRNA. Treatment of estrogen
primed ovariectomized juvenile rats with progesterone caused an initial increase
in GluR1 mRNA expression, followed by a small decrease 24 hr after treatment. In
contrast, estrogen appears to suppress levels of NMDAR1 mRNA in the AVPV, which
remained unchanged after progesterone treatment. Thus, one mechanism whereby
ovarian steroids may provide positive feedback to GnRH neurons is by altering the
sensitivity of AVPV neurons to glutamatergic activation.
PMID- 10191335
TI - Mechanisms of neural synchrony in the septohippocampal pathways underlying
hippocampal theta generation.
AB - Using urethane-anesthetized rats, 18 simultaneously recorded septohippocampal
cell pairs (36 individual cells), each classified as theta-related according to
the criteria of, were studied during four spontaneously occurring hippocampal
field conditions: (1) large amplitude irregular activity (LIA) only; (2) the
transition from LIA to theta; (3) theta only; and (4) the transition from theta
to LIA. The main objective was to study the temporal relationships and degree of
neural synchrony between the discharges of the cell pairs, using both time
averaged and time-dependent joint peristimulus time histogram correlation
techniques, during the four conditions, to determine their contribution to the
control of oscillation and synchrony (theta) in the hippocampus. The study
demonstrated that the transition from the LIA state to the theta field state in
the hippocampus required a temporal sequence of changes in theta-related cellular
activity occurring on average 500 msec preceding the transition: (1) the medial
septum inhibits hippocampal theta-OFF cells; (2) medial septal tonic theta-ON
cells provide tonic depolarizing inputs to initiate membrane potential
oscillations (MPOs) in hippocampal phasic theta-ON cells, whereas medial septal
phasic theta-ON cells synchronize the MPOs of hippocampal phasic theta-ON cells
and the discharges of hippocampal tonic theta-ON cells. Much of the time
preceding the LIA to theta transition is accounted for by recruitment of these
theta-related cell populations. Conversely, "turning off" the theta state occurs
abruptly and involves the medial septal disinhibition of hippocampal theta-OFF
cells.
PMID- 10191336
TI - Mechanisms for age-related changes of fingertip forces during precision gripping
and lifting in adults.
AB - We investigated changes across the adult life span of the fingertip forces used
to grip and lift objects and their possible causes. Grip force, relative safety
margin (grip force exceeding the minimum to avoid slip, as a fraction of slip
force), and skin slipperiness increased beginning at age 50 years. Skin
slipperiness explained relative safety margin increases until age 60 years.
Hence, after age 60 years, additional factors must elevate grip force. We argue
that one factor is impaired cutaneous afferent encoding of skin-object frictional
properties on the basis of three findings. First, only subjects 60 years and
older increased their relative safety margins when the friction of the gripped
surfaces was varied randomly versus experiments that varied only object weight.
Skin slipperiness did not account for this behavior. Second, these older subjects
scaled the initial portion of their force trajectories for the slippery surface
during experiments when friction was varied. Third, their grip force adjustments
to new surfaces were delayed approximately 100 msec as compared with young
subjects. Previous research has demonstrated that friction is signaled locally by
fast-adapting afferents (FA I afferents), which decrease in number during old
age. By contrast, adjustments triggered by object set-down, an event encoded by
FA II afferents throughout the hand and wrist, were not delayed in our old
subjects. Other findings included that anticipatory control of fingertip forces
using memory of object weight was unimpaired in old age. Finally, old and young
adults modulated their fingertip forces with equal smoothness and with similar
relative intertrial variability.
PMID- 10191337
TI - Characterization of progressive motor deficits in mice transgenic for the human
Huntington's disease mutation.
AB - Transgenic mice expressing exon 1 of the human Huntington's disease (HD) gene
carrying a 141-157 CAG repeat (line R6/2) develop a progressive neurological
phenotype with motor symptoms resembling those seen in HD. We have characterized
the motor deficits in R6/2 mice using a battery of behavioral tests selected to
measure motor aspects of swimming, fore- and hindlimb coordination, balance, and
sensorimotor gating [swimming tank, rotarod, raised beam, fore- and hindpaw
footprinting, and acoustic startle/prepulse inhibition (PPI)]. Behavioral testing
was performed on female hemizygotic R6/2 transgenic mice (n = 9) and female wild
type littermates (n = 22) between 5 and 14 weeks of age. Transgenic mice did not
show an overt behavioral phenotype until around 8 weeks of age. However, as early
as 5-6 weeks of age they had significant difficulty swimming, traversing the
narrowest square (5 mm) raised beam, and maintaining balance on the rotarod at
rotation speeds of 33-44 rpm. Furthermore, they showed significant impairment in
prepulse inhibition (an impairment also seen in patients with HD). Between 8 and
15 weeks, R6/2 transgenic mice showed a progressive deterioration in performance
on all of the motor tests. Thus R6/2 mice show measurable deficits in motor
behavior that begin subtly and increase progressively until death. Our data
support the use of R6/2 mice as a model of HD and indicate that they may be
useful for evaluating therapeutic strategies for HD, particularly those aimed at
reducing the severity of motor symptoms or slowing the course of the disease.
PMID- 10191338
TI - Human cone pigment expressed in transgenic mice yields altered vision.
AB - Genetically driven alterations in the complement of retinal photopigments are
fundamental steps in the evolution of vision. We sought to determine how a newly
added photopigment might impact vision by studying a transgenic mouse that
expresses a human cone photopigment. Electroretinogram (ERG) measurements
indicate that the added pigment works well, significantly changing spectral
sensitivity without deleteriously affecting the operation of the native cone
pigments. Visual capacities of the transgenic mice were established in behavioral
tests. The new pigment was found to provide a significant expansion of the
spectral range over which mice can perceive light, thus underlining the immediate
utility of acquiring a new photopigment. The transgenic mouse also has the
receptor basis for a novel color vision capacity, but tests show that potential
was not realized. This failure likely reflects limitations in the organizational
arrangement of the mouse retina.
PMID- 10191340
TI - Comment
PMID- 10191339
TI - Vesicular monoamine transporter-2 and aromatic L-amino acid decarboxylase enhance
dopamine delivery after L-3, 4-dihydroxyphenylalanine administration in
Parkinsonian rats.
AB - Medical therapy in Parkinson's disease (PD) is limited by the short-duration
response and development of dyskinesia that result from chronic L-3,4
dihydroxyphenylalanine (L-DOPA) therapy. These problems occur partly because the
loss of dopamine storage sites leads to erratic dopamine delivery. Vesicular
monoamine transporter-2 (VMAT-2) plays a critical role in dopamine storage by
packaging dopamine into synaptic vesicles and regulating sustained release of
dopamine. To restore the capacity to produce and store dopamine in parkinsonian
rats, primary skin fibroblast cells (PF) were genetically modified with aromatic
L-amino acid decarboxylase (AADC) and VMAT-2 genes. After incubation with L-DOPA
in culture, the doubly transduced fibroblast cells (PFVMAA) produced and stored
dopamine at a much higher level than the cells with either gene alone. PFVMAA
cells in culture released dopamine gradually in a constitutive manner.
Genetically modified fibroblast cells were grafted in parkinsonian rat striata,
and L-DOPA was systemically administered. Higher dopamine levels were sustained
for a longer duration in rats grafted with PFVMAA cells than in those grafted
with either control cells or cells with AADC alone. These findings underscore the
importance of dopamine storage capacity in determining the efficacy of L-DOPA
therapy and illustrate a novel method of gene therapy combined with precursor
administration to overcome the major obstacles of PD treatment.
PMID- 10191342
TI - Dr. Harvey rosenberg: A Fellow's perspective
PMID- 10191341
TI - Harvey S. Rosenberg: sketch of a pediatric pathologist.
PMID- 10191343
TI - Prenatal exposures and childhood cancer.
PMID- 10191344
TI - Hepatic subcapsular hematomas in fetuses and neonatal infants.
AB - In fetuses and neonates hepatic subcapsular hematomas are relatively common
lesions and may be life-threatening. Conditions previously associated with these
hematomas include trauma, coagulopathies, hypoxia, sepsis, pneumothorax, maternal
diseases, and placental lesions. In this study of 755 perinatal autopsies,
hepatic subcapsular hematomas were found in 52 (6.9%) cases, including 31
stillborn fetuses and 21 liveborn infants. The average body weight was 690 g. A
comparison group consisted of 52 temporally proximal autopsies of fetuses and
neonates without hematomas. Body weights, gender, maternal age, and stillbirth or
postnatal survival were matched as closely as possible while evaluating the
presence or absence of sepsis, pneumothorax, cerebral germinal matrix hemorrhage,
trauma, coagulopathy, placental lesions, and maternal diseases. Sepsis was
associated with 62% of the cases with hepatic subcapsular hematomas and with 25%
of the comparison group (P =.0001). Group B streptococcus infection was the most
common cause of sepsis, but many different organisms were isolated. Cerebral
germinal matrix hemorrhages were present in 35% of the cases with hematomas and
in 14% of the comparison group (P =.0001). No other lesions or conditions were
statistically different in the study group versus the comparison group. The
delicacy of the hepatic capsule and its connections to the collagen along the
sinusoids provide insight for the pathogenesis of hematomas in premature fetuses
and neonates. We conclude that sepsis is present in most perinatal cases of
hepatic subcapsular hematomas and that such patients also frequently have
cerebral germinal matrix hemorrhages. Each of these lesions is a greater hazard
among very small premature fetuses or neonates than among older fetuses and
neonates.
PMID- 10191345
TI - Spectrum of gastritis in celiac disease in childhood.
AB - Celiac disease (CD) may cause changes throughout the gastrointestinal tract. The
pathology is best described in the distal duodenum and jejunum. It is also
associated with lymphocytic gastritis (LG) and varioliform gastritis in adults
and children, but the histologic spectrum in the gastric biopsy and the clinical
implications are undefined. In this report we relate our experience with the
clinical, endoscopic, and histologic changes in gastric biopsies in CD in
childhood. Slides (hematoxylin and eosin stained) were reviewed from 33 celiac
children, 5 having had more than 1 gastric biopsy during a 7-year period. Gastric
intraepithelial lymphocyte (IEL) counts were compared with those of 10
histologically normal controls (normal range, 1-7 IEL/100 antral or body
epithelial cells) and 10 nonceliac chronic gastritis (CG) biopsies without H.
pylori (normal range, 1-19 IEL/100 antral cells), noting changes in the
epithelium and lamina propria (LP). LG was present in 29/33 initial biopsy sets.
Fifteen of 29 showed LG/CG. The IEL number was greater in LG/CG than in LG only
(27.2 +/- 9.3, n = 14 vs. 18.6 +/- 13.4, n = 15 in the antrum; 23.5 +/- 2.8, n =
4 vs. 13.0 +/- 8.4 in the body). In CD the difference between these mean values
and those of normal and nonceliac CG controls was statistically significant. In
CG/LG the inflammatory infiltrate was predominantly diffuse/superficial in the
LP; mucin depletion was noted in 11/15. The IELs were in the LG/CG range in two
CG controls. The IELs were normal at follow-up in five cases. There were no
statistically significant differences between the groups with respect to clinical
parameters or gastric endoscopic findings. No child had varioliform gastritis. We
conclude that in CD children, the stomach is endoscopically unremarkable but may
show LG, or LG/CG with or without mucin depletion, or occasionally appear normal.
Gastric histology returned to normal with gluten withdrawal. Normal gastric
histology is not typical, but does not exclude CD.
PMID- 10191346
TI - Glomerular membranopathy in children with IgA nephropathy and Henoch Schonlein
purpura.
AB - We evaluated renal biopsies from 34 children with IgA nephropathy or Henoch
Schonlein purpura to further characterize the ultrastructural features of the
glomerular membranopathy that occurs in these disorders. Focal glomerular
basement membrane damage was identified in 29 children and was severe in 4 of the
children. Alterations included focal and segmental attenuation, splitting,
duplications, and spike-like subepithelial protrusions of the lamina densa, along
with saccular glomerular microaneurysms arising at the paramesangium. Those cases
with extensive glomerular basement membrane lesions had either moderate or severe
glomerular alterations apparent by light microscopy. Over half of the cases with
glomerular membranopathy had immunohistological or ultrastructural evidence of
focal peripheral glomerular capillary wall immune deposits and electron-dense
deposits occurred at sites of glomerular basement membrane splitting. Despite the
focal attenuation of the glomerular basement membrane, we did not identify any
biopsy with findings of thin basement membrane disease. The glomerular basement
membrane ultrastructural findings we describe are characteristic of IgA
nephropathy and Henoch Schonlein purpura, are common in children with these
disorders, and are similar to the ultrastructural alterations of the basement
membrane that occur in other glomerulonephritides. These basement membrane
injuries may be inflammatory cell or immune mediated but their pathogenesis
requires further study.
PMID- 10191347
TI - Fibrous hamartoma of infancy: current review.
AB - This review examines 197 cases of fibrous hamartoma of infancy (FHI) described in
the literature and provides a detailed clinicopathologic analysis of what is
known to date of this peculiar lesion of the subcutis and lower dermis. The vast
majority of these cases occurred within the first year of life (91%). Twenty
three percent were congenital. There was a predilection for boys with a
male/female ratio of 2.4. Males and females had similar anatomic distribution
with the most common locations being the axillary region, upper arm, upper trunk,
inguinal region, and external genital area. Most cases presented as solitary
masses, but four cases of multiple separate synchronous lesions have been
reported. Most lesions presented as a painless nodule, sometimes with rapid
growth. A few cases had overlying skin changes, including alteration in
pigmentation, eccrine gland hyperplasia, and increased hair. No lesions were
reported to have familial or syndromic association, or to occur in combination
with other hamartomas. Spontaneous regression has not been reported. The
treatment of choice is local excision. Even with incomplete excision, FHI has a
low recurrence rate. Criteria for histologic diagnosis include the presence of
well-defined bundles of dense, uniform, fibrous connective tissue projecting into
fat, primitive mesenchyme arranged in nests, concentric whorls or bands, and
mature adipose tissue intimately admixed with the other components. Flow
cytometric and conventional cytogenetic studies have not been reported; these may
clarify any relationship to other fibroblastic/myofibroblastic proliferations in
children, resulting in better classification and terminology of this unique
lesion.
PMID- 10191348
TI - Approximate doubling of numbers of neurons in postnatal human cerebral cortex and
in 35 specific cytoarchitectural areas from birth to 72 months.
AB - From 1939 to 1967, J.L. Conel quantitatively studied the microscopic features of
the developing human cerebral cortex and published the findings in eight volumes.
We have constructed a database using his neuroanatomical measurements (neuronal
packing density, myelinated large fiber density, large proximal dendrite density,
somal breadth and height, and total cortical and cortical layer thickness) at the
eight age periods (0 [term birth], 1, 3, 6, 15, 24, 48, and 72 postnatal months)
he studied. In this report, we examine changes in neuron numbers over the eight
age-points for 35 von Economo areas for which Conel gave appropriate data. From
birth to 3 months postnatal age, total cortical neuron number increases 23-30%,
then falls to within 3.5% of the birth value at 24 months, supporting our
previous work showing that the observed decrease in the number of neurons per
column of cortex under a 1-mm2 cortical surface from birth to 15 months is almost
entirely due to cortical surface expansion. The present study also shows a 60-78%
increase in total cortical neuron number above the birth value from postnatal
ages 24 to 72 months. The generalization, to humans at least, of the finding of
no postnatal neurogenesis in rhesus macaques, a species belonging to a
superfamily that diverged from that of Homo sapiens more than 25 million years
ago, is not warranted until explicitly proven for humans. The data of the present
study support the existence of substantial postnatal neurogenesis in humans for
the 35 cortical areas studied.
PMID- 10191349
TI - Glomerular capillary wall basement membrane really does have laminae lucidae: A
defense.
PMID- 10191350
TI - Recent trends in chorangiomas, especially those of multiple and recurrent
chorangiomas.
AB - The nomenclature and occurrence of chorangioma of the placenta are reviewed here.
Recurrence of multiple chorangiomas has been described, but it is apparently an
uncommon or underreported event. There is a strong relationship between placental
chorangiomas and gestation at high altitude, suggesting the occurrence of
vascular growth factors induced by hypoxia. Fluid transitions may exist between
chorangioma, chorangiomatosis, and chorangiosis, although the latter is common in
diabetic pregnancies, whereas chorangiomas are not so correlated.
PMID- 10191351
TI - Renal cell carcinoma in children with diffuse cystic hyperplasia of the kidneys.
AB - We report the clinical, pathologic, and genetic features of renal malignancy in
two children with diffuse cystic hyperplasia. Both presented with massive
bilateral nephromegaly. Neither had a family history or clinical findings
suggestive of tuberous sclerosis or von Hippel-Lindau disease. The kidneys of
both children were extensively replaced by tubulocystic hyperplasia with large
eosinophilic epithelial cells. The masses of hyperplastic tissue were nodular,
compressing remnants of uninvolved renal parenchyma. Tubulopapillary carcinoma
was present in both children, one of whom had bilateral multicentric carcinoma.
No loss of heterozygosity was detected in the tumors at the TSC1, TSC2, or VHL
gene regions, and no alterations in the VHL gene were detected using single
strand conformation polymorphism analysis. These cases of bilateral renal
enlargement with diffuse cystic hyperplasia appear to represent a new clinical
syndrome that may warrant bilateral nephrectomy because of the risk of
malignancy.
PMID- 10191352
TI - Early history of pathology studies by the Intergroup Rhabdomyosarcoma Study
Group.
AB - This review chronicles the series of publications that were the result of the
willingness of pathologists and clinicians in the United States to share their
pathologic materials and clinical data on patients who were placed on treatment
protocols for rhabdomyosarcoma and related tumors over an extended period of
time. The availability of this database enabled pathologists and clinicians to
study a tumor type that is rare in individual institutions, but occurs in large
enough numbers to produce valid conclusions not otherwise possible. Furthermore,
young investigators were challenged by this opportunity and were able to spend
the necessary time to make new observations that, in retrospect, helped direct
protocol designs that produced significant improvement in patient survival. The
key factor in this process is the surrender of individual scientific prerogatives
to a small number of investigators. It is also important to recognize that the
pathologist component of these series of contributions is only a part of the
entire effort. It takes an organization of gifted, dedicated experts in many
disciplines working together. The investigators who served on the Intergroup
Rhabdomyosarcoma Group over a 25-year period eminently fulfilled this.
PMID- 10191353
TI - Isovaleric acidemia with promyelocytic myeloproliferative syndrome.
AB - Isovaleric acidemia, an autosomal recessive disorder, is due to isovaleryl
coenzyme A dehydrogenase deficiency and is one of the branched-chain
aminoacidopathies. Isovaleric acidemia may present in the neonatal period with an
acute episode of severe metabolic acidosis, ketosis, and vomiting and may lead to
coma and death in the first 2 months of life. This report concerns an infant who
presented at 10 days of age because of lethargy, poor feeding, hypothermia,
cholestasis, and thrombocytopenia, leukopenia, and profound pancytopenia. Death
occurred at 19 days of age. Autopsy showed mild fatty change in the liver and
extramedullary hematopoiesis, generalized Escherichia coli sepsis, and
myelodysplasia of the bone marrow with arrest of the myeloid series at the
promyelocytic stage. The appearance resembled promyelocytic leukemia, but the
diagnostic 15:17 translocation was not present. The maturation arrest in
granulopoiesis in isovaleric acidemia appears to be most likely due to a direct
metabolic effect on granulocyte precursor cells.
PMID- 10191354
TI - On a historical note: Dr. Virginia apgar.
PMID- 10191355
TI - Redistribution of a 120 kDa phosphoprotein in the parietal cell associated with
stimulation.
AB - When rabbit isolated gastric glands were stimulated via the cyclic AMP pathway, a
phosphorylated protein band of about 120 kDa (pp120) was markedly increased in
the apical membrane-rich fraction, concomitant with an increase in the amount of
H,K-ATPase and the phosphorylation of the cytoskeletal protein ezrin in the same
fraction. The cytosolic fraction, but not other membrane fractions, also
contained a protein with common features to the membrane-bound pp120, i.e.,
comigration in two-dimensional gels with a pI of approximately 4.5, anomalous
mobility in SDS-PAGE, reactivity to antibodies, and phosphorylation, indicating
that these two proteins were identical. The possibility that pp120 is vinculin
was completely excluded. Using antibody against pp120, this protein was found to
be almost exclusively in the gastric parietal cell. Biochemical and
immunohistochemical analyses suggest that pp120 exists mainly in the cytosol, and
that a small part of the protein binds to the apical membrane when the parietal
cell is stimulated via the cyclic AMP pathway. In the presence of histone,
purified pp120 produced phosphorylation on pp120 as well as histone. The
inhibitor profile of this kinase activity is not consistent with any known
kinase. We conclude that pp120 is closely associated with a new type of kinase,
and translocates from cytosol to the apical membrane when the parietal cell is
stimulated.
PMID- 10191356
TI - Ion selectivity of the cytoplasmic binding sites of the Na,K-ATPase: I. Sodium
binding is associated with a conformational rearrangement.
AB - To investigate Na+ binding to the ion-binding sites presented on the cytoplasmic
side of the Na,K-ATPase, equilibrium Na+-titration experiments were performed
using two fluorescent dyes, RH421 and FITC, to detect protein-specific actions.
Fluorescence changes upon addition of Na+ in the presence of various Mg2+
concentrations were similar and could be fitted with a Hill function. The half
saturating concentrations and Hill coefficients determined were almost identical.
As RH421 responds to binding of a Na+ ion to the third neutral site whereas FITC
monitors conformational changes in the ATP-binding site or its environment, this
result implies that electrogenic binding of the third Na+ ion is the trigger for
a structural rearrangement of the ATP-binding moiety. This enables enzyme
phosphorylation, which is accompanied by a fast occlusion of the Na+ ions and
followed by the conformational transition E1/E2 of the protein. The coordinated
action both at the ion and the nucleotide binding sites allows for the first time
a detailed formulation of the mechanism of enzyme phosphorylation that occurs
only when three Na+ ions are bound.
PMID- 10191358
TI - Sodium recirculation and isotonic transport in toad small intestine.
AB - Isolated small intestine of toad (Bufo bufo) was mounted on glass tubes for
perfusion studies with oxygenated amphibian Ringer's solution containing glucose
and acetate. Under open-circuit conditions (Vt = -3.9 +/- 1.8 mV, N = 14) the
preparation generated a net influx of 134Cs+. The time course of unidirectional
134Cs+-fluxes was mono-exponential with similar rate constants for influx and
outflux when measured in the same preparation. The flux-ratio was time invariant
from the beginning of appearance of the tracers to steady state was achieved.
Thus, just a single pathway, the paracellular pathway, is available for
transepithelial transport of Cs+. From the ratio of unidirectional Cs+-fluxes the
paracellular force was calculated to be, 18.2 +/- 1.5 mV (N = 6), which is
directed against the small transepithelial potential difference. The paracellular
netflux of cesium ions, therefore, is caused by solvent drag. The flux of 134Cs+
entering and trapped by the cells was of a magnitude similar to that passing the
paracellular route. Therefore, independent of the convective flux of 134Cs+,
every second 134Cs+ ion flowing into the lateral space was pumped into the cells
rather than proceeding, via the low resistance pathway, to the serosal bath. It
is thus indicated that the paracellular convective flow of 134Cs+ is driven by
lateral Na+/K+-pumps. Transepithelial unidirectional 42K+ fluxes did not reach
steady state within an observation period of 70 min, indicating that components
of the fluxes in both directions pass the large cellular pool of potassium ions.
The ratio of unidirectional 24Na+ fluxes was time-variant and declined from an
initial value of 3.66 +/- 0.34 to a significantly smaller steady-state value of
2.57 +/- 0.26 (P < 0.001, N = 5 paired observations), indicating that sodium ions
pass the epithelium both via the paracellular and the cellular pathway.
Quantitatively, the larger ratio of paracellular Na+ fluxes, as compared to that
of paracellular Cs+ fluxes, is compatible with convective flow of the two alkali
metal ions through the same population of water-filled pores. With a new set of
equations, the fraction of the sodium flux passing the basement membrane barrier
of the lateral space that is recirculated through the cellular compartment is
estimated. This fraction was, on average, 0.72 +/- 0.03 (N = 5). It is concluded
that isotonicity of the transportate can be maintained by producing a hypertonic
fluid emerging from the lateral space combined with reuptake of salt via the
cells.
PMID- 10191357
TI - Cystic fibrosis transmembrane conductance regulator (CFTR) confers glibenclamide
sensitivity to outwardly rectifying chloride channel (ORCC) in Hi-5 insect cells.
AB - Increasing evidence is now accumulating for the involvement of the cystic
fibrosis transmembrane conductance regulator (CFTR) in the control of the
outwardly rectifying chloride channel (ORCC). We have examined the sensitivity of
ORCC to the sulfonylurea drug glibenclamide in Hi-5 (Trichoplusia ni) insect
cells infected with recombinant baculovirus expressing either wild-type CFTR,
DeltaF508-CFTR or E. coli beta galactosidase cDNA and in control cells either
infected with virus alone or uninfected. Iodide efflux and single channel patch
clamp experiments confirmed that forskolin and 1-methyl-3-isobutyl xanthine
(IBMX) or 7-methyl-1,3 dipropyl xanthine (DPMX) activate CFTR channels (unitary
conductance: 9.1 +/- 1.6 pS) only in cells expressing CFTR. In contrast, we
identified 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid (SITS)
sensitive ORCC in excised membrane patches in any of the cells studied, with
similar conductance (22 +/- 2.5 pS at -80 mV; 55 +/- 4.1 pS at +80 mV) and
properties. In the presence of 500 microm SITS, channel open probability (Po) of
ORCC was reversibly reduced to 0.05 +/- 0.01 in CFTR-cells, to 0.07 +/- 0.02 in
non-CFTR expressing cells and to 0.05 +/- 0.02 in DeltaF508-cells. In Hi-5 cells
that did not express CFTR, glibenclamide failed to inhibit ORCC activity even at
high concentrations (100 microm), whereas 500 microm SITS reversibly inhibited
ORCC. In contrast in cells expressing CFTR or DeltaF508, glibenclamide dose
dependently (IC50 = 17 microm, Hill coefficient 1.2) and reversibly inhibited
ORCC. Cytoplasmic application of 100 microm glibenclamide reversibly reduced Po
from 0.88 +/- 0.03 to 0.09 +/- 0.02 (wash: Po = 0.85 +/- 0.1) in CFTR cells and
from 0.89 +/- 0.05 to 0.08 +/- 0.05 (wash: Po = 0.87 +/- 0.1) in DeltaF508 cells.
In non-CFTR expressing cells, glibenclamide (100 microm) was without effect on Po
(control: Po = 0. 89 +/- 0.09, glib.: Po = 0.86 +/- 0.02; wash: Po = 0.87 +/-
0.05). These data strongly suggest that the expression of CFTR confers
glibenclamide sensitivity to the ORCC in Hi-5 cells.
PMID- 10191359
TI - Comparison of amphibian and human ClC-5: similarity of functional properties and
inhibition by external pH.
AB - Loss of function mutations of the renal chloride channel, ClC-5, have been
implicated in Dent's disease, a genetic disorder characterized by low weight
proteinuria, hypercalciuria, nephrolithasis and, in some cases, eventual renal
failure. Recently, our laboratory used an RT-PCR/RACE cloning strategy to isolate
an amphibian cDNA from the renal epithelial cell line A6 that had high homology
to human ClC-5. We now report a full-length native ClC-5 clone (xClC-5,
containing 5' and 3' untranslated regions) isolated by screening a cDNA library
from A6 cells that was successfully expressed in Xenopus oocytes. In addition, we
compared the properties of xClC-5 and hClC-5 using isogenic constructs of xClC-5
and hClC-5 consisting of the open reading frame subcloned into an optimized
Xenopus expression vector. Expression of the full-length "native" xClC-5 clone
resulted in large, strongly rectifying, outward currents that were not
significantly affected by the chloride channel blockers DIDS, DPC, and 9AC. The
anion conductivity sequence was NO-3 > Cl- = I- > HCO-3 >> glutamate for xClC-5
and NO-3 > Cl- > HCO-3 > I- >> glutamate for hClC-5. Reduction of the
extracellular pH (pHo) from 7.5 to 5.7 inhibited outward ClC-5 currents by 27 +/-
9% for xClC-5 and 39 +/- 7% for hClC-5. The results indicate that amphibian and
mammalian ClC-5 have highly similar functional properties. Unlike hClC-5 and most
other ClC channels, expression of xClC-5 in oocytes does not require the removal
of its untranslated 5' and 3' regions. Acidic solutions inhibited both amphibian
and human ClC-5 currents, opposite to the stimulatory effects of low external pH
on other ClC channels, suggesting a possibly distinct regulatory mechanism for
ClC-5 channels.
PMID- 10191360
TI - Differential asparagine-linked glycosylation of voltage-gated K+ channels in
mammalian brain and in transfected cells.
AB - Glycosylation of ion channel proteins dramatically impacts channel function. Here
we characterize the asparagine (N)-linked glycosylation of voltage-gated K+
channel alpha subunits in rat brain and transfected cells. We find that in brain
Kv1.1, Kv1.2 and Kv1.4, which have a single consensus glycosylation site in the
first extracellular interhelical domain, are N-glycosylated with sialic acid-rich
oligosaccharide chains. Kv2.1, which has a consensus site in the second
extracellular interhelical domain, is not N-glycosylated. This pattern of
glycosylation is consistent between brain and transfected cells, providing
compelling support for recent models relating oligosaccharide addition to the
location of sites on polytopic membrane proteins. The extent of processing of N
linked chains on Kv1.1 and Kv1.2 but not Kv1.4 channels expressed in transfected
cells differs from that seen for native brain channels, reflecting the different
efficiencies of transport of K+ channel polypeptides from the endoplasmic
reticulum to the Golgi apparatus. These data show that addition of sialic acid
rich N-linked oligosaccharide chains differs among highly related K+ channel
alpha subunits, and given the established role of sialic acid in modulating
channel function, provide evidence for differential glycosylation contributing to
diversity of K+ channel function in mammalian brain.
PMID- 10191361
TI - Effect of two tyrosine mutations on the activity and regulation of the renal type
II Na/Pi-cotransporter expressed in oocytes.
AB - The rat renal type II Na/Pi-cotransporter (NaPi2), which is regulated by
mechanisms involving endocytosis and lysosomal degradation, contains two
sequences that show high homology with two tyrosine (Y)-based consensus motifs
previously reported to be involved in such intracellular trafficking: GY402FAM
matching the consensus sequence GYXXZ, and Y509RWF matching the motif YXXO.
Mutations of any of these two Y nearly abolished the NaPi2 mediated 32Pi-uptake
after cRNA-injection into oocytes. The mechanisms underlying these defects are
however different. Mutation of the Y402 results in a lack of glycosylation and
reduced surface expression of the cotransporter, that are specific for the Y402
mutation since substitution of the neighboring F403 did not have any effect. The
inhibitory effect of the Y509 mutation is related to a functional inactivation of
the protein expressed in the plasma membrane; mutation of the neighboring R510
also led to a decrease in the cotransporter activity. Pharmacological activation
of the protein kinase C cascade by DOG induced the retrieval of both wild-type
(WT) as well as Y509 cotransporters from the oocyte plasma membrane. These data
suggest that the Y402 is important for the surface expression whereas Y509 for
the function of the type II Na/Pi-cotransporter expressed in oocytes. Y509 seems
not to be involved in the membrane retrieval of the cotransporter.
PMID- 10191362
TI - Thermoreception of Paramecium: different Ca2+ channels were activated by heating
and cooling.
AB - A Paramecium cell responded to heat and cold stimuli, exhibiting increased
frequency of directional changes in its swimming behavior. The increase in the
frequency of directional changes was maintained during heating, but was transient
during cooling. Although variations were large, as expected with this type of
electrophysiological recording, results consistently showed a sustained
depolarization of deciliated cells in response to heating. Depolarizations were
also consistently observed upon cooling. However, these depolarizations were
transient and not continuous throughout the cooling period. These depolarizations
were lost or became small in Ca2+-free solutions. In a voltage-clamped cell,
heating induced a continuous inward current and cooling induced a transient
inward current under conditions where K+ currents were suppressed. The heat
induced inward current was not affected significantly by replacing extracellular
Ca2+ with equimolar concentrations of Ba2+, Sr2+, Mg2+, or Mn2+, and was lost
upon replacing with equimolar concentration of Ni2+. On the other hand, the cold
induced inward current was not affected significantly by Ba2+, or Sr2+, however
the decay of the inward current was slowed and was lost or became small upon
replacing with equimolar concentrations of Mg2+, Mn2+, or Ni2+. These results
indicate that Paramecium cells have heat-activated Ca2+ channels and cold
activated Ca2+ channels and that the cold-activated Ca2+ channel is different
from the heat-activated Ca2+ channel in the ion selectivity and the calcium
dependent inactivation.
PMID- 10191364
TI - : The Impact of Calcium Dobesilate on Vascular Endothelial Dysfunction.
PMID- 10191365
TI - Antioxidant-Angioprotective Actions of Calcium Dobesilate in Diabetic Rats.
AB - Calcium dobesilate was tested in rats with streptozotocin(STZ)-induced diabetes,
for its angioprotective properties against the extravasation of plasma Evans blue
towards the peritoneal cavity, induced in situ by the free radical generating
agent phenazine methosulfate (PMS). In diabetic rats pretreated with a single
oral dose of 50 and 200 mg/kg calcium dobesilate, PMS-induced Evans blue
extravasation was respectively reduced by 60 and 100% with respect to values in
vehicle-treated animals (p < 0.05 and p < 0.01 respectively; in diabetic rats,
PMS-induced Evans blue peritoneal extravasation was double as in control animals
= 0.0814 +/- 0.019 vs. 0.0396 +/- 0.0083 h-1, p < 0.05). In diabetic rats
pretreated with 50 and 100 mg/kg/day of calcium dobesilate for 7 days, PMS
induced Evans blue extravasation was respectively reduced by 56 and 80% with
respect to values in vehicle-treated animals (p < 0.01 and p < 0.001
respectively). In conclusion, calcium dobesilate p.o. significantly and dose
dependently antagonized the increase in capillary permeability induced by an
oxidative stress in the peritoneal cavity of diabetic rats. These results further
suggest that the antioxidant properties of calcium dobesilate can be involved, at
least in part, in its angioprotective actions in humans.
PMID- 10191363
TI - Small synthetic peptides homologous to segments of the first external loop of
occludin impair tight junction resealing.
AB - This study shows that resealing of opened tight junctions (TJs) is impaired by
interaction with oligopeptides homologous to the external domain of chick
occludin. The experiments were carried out with confluent A6 cell monolayers
grown on collagen supports under stable transepithelial electrical resistance
(TER). The monolayers were bathed on the apical side with a 75 mm KCl solution
and on the basolateral side by NaCl-Ringer's solution. TJ opening was induced by
basolateral Ca2+ removal and was characterized by a marked drop of TER. The
reintroduction of Ca2+ triggered junction resealing as indicated by an elevation
of TER to control values. Custom-made peptides SNYYGSGLSY (corresponding to the
residues 100 to 109) and SNYYGSGLS (residues 100 to 108), homologous to segments
of the first external loop of chick occludin molecule, impaired junction
resealing when the peptides were included in the apical bathing fluid
(concentrations in the range of 0.5 to 1.5 mg/ml). Peptide removal from the
apical solution usually triggered a slow recovery of TER, indicating a slow
recovery of the TJ seal. Changes in localization of ZO-1, a cytoplasmic protein
that underlies the membrane at the TJs, were evaluated immunocytochemically
following Ca2+ removal and reintroduction. The presence or absence of the
oligopeptides showed no influence on the pattern of change of ZO-1 localization.
These observations support the hypothesis that the TJ seal results from the
interaction of specific homologous segments of occludin on the surface of
adjacent cells. Additionally, our results show that small peptides homologous to
segments of the occludin first external loop can be used as specific reagents to
manipulate the permeability of tight junctions.
PMID- 10191367
TI - Prevention of Oxidation and Apoptosis in Human Peripheral Blood Mononuclear Cells
Exposed to Calcium Dobesilate.
AB - The antioxidant effects of calcium dobesilate (CD) (Doxium(R)) were investigated
in relation to the oxidative status, apoptosis, and in vitro proliferation of
human peripheral blood mononuclear cells (PBMC) isolated from healthy donors.
Calcium dobesilate alone did not modify cell growth in vitro until it reached 10
uM. This molecule counteracted oxidative damage generated by the highly reducing
sugar 2-deoxy-D-ribose (dR) and was shown to reduce apoptosis by delaying both
membrane permeability changes and DNA fragmentation. Calcium dobesilate (10 uM)
was effective in a time-dependent manner on several parameters, representative of
the cellular oxidative status. In particular, CD significantly increased the
activity of glutathione S-transferase (GST) after 3 days of treatment and also
the activity of gamma-glutamyltransferase (gamma-GT). Both of these enzymes are
known to be involved in the glutathione (GSH) metabolic cycle. This enzymatic
behavior was reversed after 7 days of treatment, with a significant GST decrease
and a gamma-GT activation. After 7 days of CD exposure, the intracellular GSH
content was enhanced and this resulted in a dramatic decrease of lipid
peroxidation, underlining the powerful antioxidant properties of CD in human
PBMC.
PMID- 10191366
TI - Involvement of Nitric Oxide in the Inhibition of Aortic Smooth Muscle Cell
Proliferation by Calcium Dobesilate.
AB - Vascular smooth muscle cell (SMC) proliferation is a key process in the
pathogenesis of atherosclerosis. Numerous factors are involved in the regulation
of SMC growth. Nitric oxide (NO) induces the inhibition of SMC proliferation
whereas oxidized low-density lipoproteins (LDL) have a mitogenic effect. Calcium
dobesilate (Doxium) is an angioprotective agent for treating vascular diseases.
It has been shown to increase NO production and to have antioxidant properties
but its mechanism of action is not yet fully understood. This study investigated
the effect of calcium dobesilate on proliferation of rat aortic SMC in culture.
Proliferation was evaluated by cell number and DNA synthesis. Orally administered
calcium dobesilate (30, 100, or 200 mg/kg/day for 7 days) induced a dose
dependent decrease of proliferation of SMC in primary culture compared with
controls. In vitro treatment with calcium dobesilate (0.05-5 mM) inhibited both
DNA synthesis and proliferation in a time- and concentration-dependent manner. In
both ex vivo and in vitro models, the inhibition was reversible upon removal of
the drug. Calcium dobesilate also stimulated NO production and NO synthase
activity. Inhibitors of NO synthesis attenuated the inhibitory effect of calcium
dobesilate (300 uM) on DNA synthesis. In addition, calcium dobesilate (2.5-40 uM)
induced a dose-dependent protection of cooper-induced LDL oxidation. These
results showed that calcium dobesilate inhibits SMC proliferation, partly by a NO
dependent mechanism, and suggest that it could be effective in the treatment of
pathological disorders associated with vascular SMC proliferation.
PMID- 10191368
TI - Study of Calcium Dobesilate in Diabetic Rats.
AB - According to the World Health Organization (WHO) 74% of diabetic patients die of
vascular complications. Previous reports have shown that endothelium-dependent
relaxation of diabetic vasculature is more sensitive to free radical-induced
injury. Calcium dobesilate (DOBE) has been successfully used in the treatment of
diabetic retinopathy. The aims of this study were to investigate the in vivo and
ex vitro effects of DOBE on both contractile and relaxing responses in isolated
diabetic rat aorta. Four groups of rats were used: Wistar rats (Group 0);
spontaneously diabetic rats (BB/wor rats) (Group 1); BB/wor rats treated with
DOBE 50 mg/kg/day (Group 2); and BB/wor rats treated with 500 mg/kg/day (Group
3). At 180 days after the development of diabetes, the animals were killed and
the thoracic aorta were isolated, cleaned off, and mounted in an organ chamber.
Two groups of experiments were carried out. In the first group (in vitro),
incubation with DOBE 10(-4) in aortic rings isolated from BB/wor rats decreased
the contraction induced by noradrenaline (NA) 10(-6) M (1.21 +/- 0.11 g vs 0.67
+/- 0.01 g P < 0.01, n = 8 in diabetic rings with or without the presence of DOBE
10(-4) M, respectively), and this decrease was prevented by propranolol 10(-6) M
(1.20 +/- 0.6 g). DOBE 10(-5) and 10(-4) M increased the endothelium-dependent
relaxation induced by ACh in BB/wor rats [the maximal relaxation with ACh 10(-5)
M was 50.0 +/- 5.1 vs 72.0 +/- 11.0 (p < 0.05, n = 8) and 69.0 +/- 7.8 (p < 0.05,
n = 8) in BB/wor rats and after the incubation with DOBE 10(-5) and 10(-4) M,
respectively], however, incubation with DOBE did not modify the endothelium
independent relaxation in these rats. In the second part of the study (ex vitro),
we found an increase in the endothelium-dependent relaxation in arteries from
diabetic rats treated with DOBE (Groups 2) compared with Group 1 (BB/wor rats)
although we did not find any improvement in the endothelium-independent
relaxation. Thus, in spontaneously diabetic rats, DOBE restored endothelium
dependent, but not independent, relaxation to normal and also decreased the
contractile responses induced by NA through a mechanism that involves beta
adrenergic receptors.
PMID- 10191369
TI - Effects of Magnesium Dobesilate on Nitric Oxide Synthase Activity in Endothelial
Cells.
AB - This study was done to determine the effects of the angioprotective agent
dobesilate on expression and activity on the constitutive nitric oxide synthase
(ecNOS) in resident endothelial cells, as well as of the inducible nitric oxide
synthase (iNOS) in cytokine-activated endothelial cells, by recording, in culture
supernatants, the concentrations of citrulline as a reaction product of both
enzymes. In capillary, microvascular, and macrovascular endothelial cells, Mg
dobesilate incubation (0.25-1 mM) for 24 hours led to a highly significant
concentration-correlating increase in ecNOS activities. These increases were not
due to iNOS expression, and with cytokine-activated endothelial cell cultures
that do express iNOS only moderate effects with little or no concentration
dependency were seen. Addition of the NOS inhibitor NG-monomethyl-L-arginine
(NMA) significantly suppresses citrulline formation in all cultures as evidence
for the enzyme specificity.
PMID- 10191370
TI - Temporal-spatial feature of gait after traumatic brain injury.
AB - The temporal-spatial characteristics of the gait of patients with traumatic brain
injury (TBI) were investigated and compared with those of normal gait and the
gait of stroke survivors. A slower walking velocity is evident in the TBI
population when compared with normal. The average walking speed of TBI survivors
is faster than that of stroke patients and is mainly related to a longer step
length. TBI survivors produce a gait pattern with a prolonged stance period for
the unaffected limb, without prolonged stance period for the affected limb, and a
shorter step length for the unaffected limb.
PMID- 10191371
TI - The use of gait analysis for surgical recommendations in traumatic brain injury.
AB - Traumatic brain injury causes unpredictable errors in the patient's gait by
introducing varying mixtures of spasticity, contractures, primitive flexion and
extension synergies, and impaired selective control. Surgical release or transfer
of the offending muscles can improve the patient's ability to walk if functional
errors have been accurately identified. While clinical testing is inadequate,
instrumented motion analysis and dynamic electromyography can supply an accurate
definition of the abnormalities in muscle action and provide guidelines for
distinguishing local from referred motion errors. Examples of the diagnostic
differences related to the equinovarus foot and the common types of knee
dysfunction are presented.
PMID- 10191372
TI - An algorithm to assess stiff-legged gait in traumatic brain injury.
AB - Spastic paretic stiff-legged gait is a frequently encountered gait problem in
patients with traumatic brain injury, as well as in many other patients with
upper motor neuron disease. Formerly, spasticity of the quadriceps was considered
to be the sole cause of stiff-legged gait. Quantitative gait analysis, however,
may implicate hip flexor weakness or poor ankle mechanics as the cause of stiff
legged gait. We discuss the use of an algorithm to evaluate stiff-legged gait in
traumatic brain injury using a quantitative gait analysis system such that the
specific etiology of stiff-legged gait can be identified and can serve as the
basis of a treatment plan.
PMID- 10191373
TI - A novel method for locomotion training.
AB - This article describes a novel therapeutic system for locomotion training and
learning for patients with a wide range of neurological and musculoskeletal
disorders. The technique embraces the notion that locomotion therapy should be
goal oriented and task specific. The task specificity includes a partial weight
bearing device that permits the posture/equilibrium, movement, and weight-bearing
components of gait function to operate concurrently, even in patients with
serious deficits. In addition, it allows interaction with therapists and others
to facilitate locomotion control, particularly during the early stages of gait
therapy. Neurobiological bases for this technique and early clinical results are
discussed, and two case studies of patients with traumatic brain injury (TBI) are
presented. Although well-designed efficacy studies are needed, clearly this
therapeutic approach to locomotor disorders among TBI patients meets the various
criteria for recovery of gait function established in this article.
PMID- 10191374
TI - Improving calf muscle strength in patients with spastic equinovarus deformity by
transfer of the long toe flexors to the Os calcis.
AB - The split tibialis anterior tendon transfer (SPLATT), Achilles tendon
lengthening, and toe flexor release are proven and effective procedures for
correcting a spastic equinovarus deformity of the foot. Paresis is a prominent
feature of upper motoneuron syndrome. Lengthening the Achilles tendon, although
necessary to correct the equinus, further weakens the gastrocnemius-soleus muscle
group. The calf paresis commonly results in the need for an ankle-foot orthosis
(AFO) during ambulation. Previous studies have shown that despite the correction
of the equinovarus deformity, only one third of patients were able to ambulate
without an AFO. The need for continued use of an AFO was because of insufficient
calf strength to stabilize the tibia during late stance when the body mass is
anterior to the ankle joint. This study prospectively evaluated the results of
transfer of the flexor hallucis longus (FHL) and flexor digitorum longus (FDL) to
the os calcis in 30 patients. The transfer was done in an effort to augment the
strength of the gastrocnemius-soleus muscle complex. Twenty-five patients in
group I (the control group) underwent SPLATT, Achilles tendon lengthening, and
toe flexor release. Thirty patients in group II (the study group) underwent the
identical procedures plus the additional FHL and FDL transfer to the os calcis.
Postoperatively, the varus and toe flexion deformities were corrected in all
feet. In group II, two feet had a mild residual equinus that did not interfere
with ambulation. Of the 11 patients who were not independent community ambulators
in group I, 7 (64%) improved ambulatory status by at least one level after
surgery. Of the 15 patients who were not independent community ambulators in
group II, 14 (93%) improved ambulatory status by at least one level after
surgery. In group I, 10 of 25 (40%) of the patients were brace free at follow-up.
In group II, 21 of 30 (70%) were brace free at follow-up (c2, P =.025). These
results indicate that the addition of an FHL and FDL transfer to the os calcis at
the time of SPLATT, Achilles tendon lengthening, and toe flexor release improves
calf strength and allows greater increase in function and less reliance on
orthotics.
PMID- 10191376
TI - TBI model system grants
AB - The Traumatic Brain Injury (TBI) Model Systems Program has been funded by the
National Institute on Disability and Rehabilitation Research (NIDRR) since 1987.
Until recently, this program has consisted of four centers that conducted
priority-focused research on specific aspects of TBI and analyzed data on the
basis of a uniform, comprehensive national database. In 1997, $5 million in
additional funding was allocated for the expansion of this program. In October
1998, after a competitive renewal process, a total of 12 new centers were
awarded, bringing the total TBI Model Systems to 17. In addition to the creation
of new centers, funding was provided for specific collaborative research projects
and increased resources for the TBI National Data Center. Below are the abstracts
for both the newly funded systems and the existing systems.
PMID- 10191375
TI - Summary report: evidence for the effectiveness of rehabilitation for persons with
traumatic brain injury.
AB - We evaluated the evidence for effectiveness of rehabilitation methods throughout
the phases of recovery from traumatic brain injury (TBI) in adults. MEDLINE,
HealthSTAR, CINAHL, PsycINFO, and the Cochrane Library were searched, and a total
of 3,098 abstracts were reviewed. The strongest studies were critically appraised
and their data placed in evidence tables. Results showed that to determine the
effectiveness of rehabilitation interventions for persons with TBI, a commitment
must be made to population-based studies, strong controlled research design,
standardization of measures, adequate statistical analysis, and specification of
health outcomes of importance to persons with TBI and their families.
PMID- 10191377
TI - TBI state demonstration grants
AB - In 1996, Congress enacted Public Law 104-166, the Traumatic Brain Injury (TBI)
Act, to provide for the conduct of expanded studies and the establishment of
innovative programs with respect to TBI. As part of the Act, the Health Resources
and Services Administration (HRSA), Maternal and Child Health Bureau (MCHB), is
responsible for implementing the TBI State Demonstration Grant Program to improve
health and other services regarding persons with TBI and their families.
Currently, the TBI State Demonstration Grant Program includes two categories of
grants: Planning and Implementation. Planning Grants are available to states that
wish to develop the core components necessary to improve the overall
infrastructure of the state system. These four components include establishment
of an advisory board, the identification of a coordinating agency and designated
staff, the completion of a comprehensive needs/resource assessment, and the
development of a statewide action plan. Those states that can successfully
demonstrate core capacity are eligible for grants in the Implementation category.
Implementation grants provide resources to implement statewide systems and models
that will improve and enhance access to comprehensive and coordinated services
for individuals with TBI and their families.
PMID- 10191378
TI - Management of spasticity in children: part 2: oral medications and intrathecal
baclofen.
PMID- 10191379
TI - Metabolic engineering.
PMID- 10191380
TI - Increasing the flux in metabolic pathways: A metabolic control analysis
perspective
AB - The problems of engineering increased flux in metabolic pathways are analyzed in
terms of the understanding provided by metabolic control analysis. Over
expression of a single enzyme is unlikely to be effective unless it is known to
have a high flux control coefficient, which can be used as an approximate
predictive tool. This is likely to rule out enzymes subject to feedback
inhibition, because it transfers control downstream from the inhibited enzyme to
the enzymes utilizing the feedback metabolite. Although abolishing feedback
inhibition can restore flux control to an enzyme, it is also likely to cause
large increases in the concentrations of metabolic intermediates. Simultaneous
and coordinated over-expression of most of the enzymes in a pathway can, in
principle, produce substantial flux increases without changes in metabolite
levels, though technically it may be difficult to achieve. It is, however, closer
to the method used by cells to change flux levels, where coordinated changes in
the level of activity of pathway enzymes are the norm. Another option is to
increase the demand for the pathway product, perhaps by increasing its rate of
excretion or removal. Copyright 1998 John Wiley & Sons, Inc.
PMID- 10191381
TI - Metabolic engineering: techniques for analysis of targets for genetic
manipulations.
AB - Metabolic engineering has been defined as the purposeful modification of
intermediary metabolism using recombinant DNA techniques. With this definition
metabolic engineering includes: (1) inserting new pathways in microorganisms with
the aim of producing novel metabolites, e.g., production of polyketides by
Streptomyces; (2) production of heterologous peptides, e.g., production of human
insulin, erythropoitin, and tPA; and (3) improvement of both new and existing
processes, e.g., production of antibiotics and industrial enzymes. Metabolic
engineering is a multidisciplinary approach, which involves input from chemical
engineers, molecular biologists, biochemists, physiologists, and analytical
chemists. Obviously, molecular biology is central in the production of novel
products, as well as in the improvement of existing processes. However, in the
latter case, input from other disciplines is pivotal in order to target the
genetic modifications; with the rapid developments in molecular biology, progress
in the field is likely to be limited by procedures to identify the optimal
genetic changes. Identification of the optimal genetic changes often requires a
meticulous mapping of the cellular metabolism at different operating conditions,
and the application of metabolic engineering to process optimization is,
therefore, expected mainly to have an impact on the improvement of processes
where yield, productivity, and titer are important design factors, i.e., in the
production of metabolites and industrial enzymes. Despite the prospect of
obtaining major improvement through metabolic engineering, this approach is,
however, not expected to completely replace the classical approach to strain
improvement-random mutagenesis followed by screening. Identification of the
optimal genetic changes for improvement of a given process requires analysis of
the underlying mechanisms, at best, at the molecular level. To reveal these
mechanisms a number of different techniques may be applied: (1) detailed
physiological studies, (2) metabolic flux analysis (MFA), (3) metabolic control
analysis (MCA), (4) thermodynamic analysis of pathways, and (5) kinetic modeling.
In this article, these different techniques are discussed and their applications
to the analysis of different processes are illustrated.
PMID- 10191382
TI - A structured approach for selection among candidate metabolic network models and
estimation of unknown stoichiometric coefficients.
AB - A metabolic network model is one of the cornerstones of the emerging Metabolic
Engineering methodology. In this article, special attention is therefore, given
to the phase of model building. A five-stage structured approach to metabolic
network modeling is introduced. The basic steps are: (1) to collect a priori
knowledge on the reaction network and to build candidate network models, (2) to
perform an a priori check of the model, (3) to estimate the unknown parameters in
the model, (4) to check the identified model for acceptability from a biological
and thermodynamic point of view, and (5) to validate the model with new data. The
approach is illustrated with a growth system involving baker's yeast growing on
mixtures of substrates. Special attention is given to the central uncertainties
in metabolic network modeling, i.e., estimation of energetic parameters in the
network and the choice of the source of anabolic reducing equivalents NADPH.
PMID- 10191383
TI - On-line metabolic pathway analysis based on metabolic signal flow diagram.
AB - In this work, an integrated modeling approach based on a metabolic signal flow
diagram and cellular energetics was used to model the metabolic pathway analysis
for the cultivation of yeast on glucose. This approach enables us to make a clear
analysis of the flow direction of the carbon fluxes in the metabolic pathways as
well as of the degree of activation of a particular pathway for the synthesis of
biomaterials for cell growth. The analyses demonstrate that the main metabolic
pathways of Saccharomyces cerevisiae change significantly during batch culture.
Carbon flow direction is toward glycolysis to satisfy the increase of requirement
for precursors and energy. The enzymatic activation of TCA cycle seems to always
be at normal level, which may result in the overflow of ethanol due to its
limited capacity. The advantage of this approach is that it adopts both virtues
of the metabolic signal flow diagram and the simple network analysis method,
focusing on the investigation of the flow directions of carbon fluxes and the
degree of activation of a particular pathway or reaction loop. All of the
variables used in the model equations were determined on-line; the information
obtained from the calculated metabolic coefficients may result in a better
understanding of cell physiology and help to evaluate the state of the cell
culture process.
PMID- 10191384
TI - Experimental determination of group flux control coefficients in metabolic
networks
AB - Grouping of reactions around key metabolite branch points can facilitate the
study of metabolic control of complex metabolic networks. This top-down Metabolic
Control Analysis is exemplified through the introduction of group (flux, as well
as concentration) control coefficients whose magnitudes provide a measure of the
relative impact of each reaction group on the overall network flux, as well as on
the overall network stability, following enzymatic amplification. In this
article, we demonstrate the application of previously developed theory to the
determination of group flux control coefficients. Experimental data for the
changes in metabolic fluxes obtained in response to the introduction of six
different environmental perturbations are used to determine the group flux
control coefficients for three reaction groups formed around the
phosphoenolpyruvate/pyruvate branch point. The consistency of the obtained group
flux control coefficient estimates is systematically analyzed to ensure that all
necessary conditions are satisfied. The magnitudes of the determined control
coefficients suggest that the control of lysine production flux in
Corynebacterium glutamicum cells at a growth base state resides within the lysine
biosynthetic pathway that begins with the PEP/PYR carboxylation anaplorotic
pathway. Copyright 1998 John Wiley & Sons, Inc.
PMID- 10191385
TI - Application of mathematical tools for metabolic design of microbial ethanol
production.
AB - Many attempts to engineer cellular metabolism have failed due to the complexity
of cellular functions. Mathematical and computational methods are needed that can
organize the available experimental information, and provide insight and guidance
for successful metabolic engineering. Two such methods are reviewed here. Both
methods employ a (log)linear kinetic model of metabolism that is constructed
based on enzyme kinetics characteristics. The first method allows the description
of the dynamic responses of metabolic systems subject to spatiotemporal
variations in their parameters. The second method considers the product-oriented,
constrained optimization of metabolic reaction networks using mixed-integer
linear programming methods. The optimization framework is used in order to
identify the combinations of the metabolic characteristics of the glycolytic
enzymes from yeast and bacteria that will maximize ethanol production. The
methods are also applied to the design of microbial ethanol production
metabolism. The results of the calculations are in qualitative agreement with
experimental data presented here. Experiments and calculations suggest that, in
resting Escherichia coli cells, ethanol production and glucose uptake rates can
be increased by 30% and 20%, respectively, by overexpression of a deregulated
pyruvate kinase, while increase in phosphofructokinase expression levels has no
effect on ethanol production and glucose uptake rates.
PMID- 10191386
TI - How will bioinformatics influence metabolic engineering?
AB - Ten microbial genomes have been fully sequenced to date, and the sequencing of
many more genomes is expected to be completed before the end of the century. The
assignment of function to open reading frames (ORFs) is progressing, and for some
genomes over 70% of functional assignments have been made. The majority of the
assigned ORFs relate to metabolic functions. Thus, the complete genetic and
biochemical functions of a number of microbial cells may be soon available. From
a metabolic engineering standpoint, these developments open a new realm of
possibilities. Metabolic analysis and engineering strategies can now be built on
a sound genomic basis. An important question that now arises; how should these
tasks be approached? Flux-balance analysis (FBA) has the potential to play an
important role. It is based on the fundamental principle of mass conservation. It
requires only the stoichiometric matrix, the metabolic demands, and some strain
specific parameters. Importantly, no enzymatic kinetic data is required. In this
article, we show how the genomically defined microbial metabolic genotypes can be
analyzed by FBA. Fundamental concepts of metabolic genotype, metabolic phenotype,
metabolic redundancy and robustness are defined and examples of their use given.
We discuss the advantage of this approach, and how FBA is expected to find uses
in the near future. FBA is likely to become an important analysis tool for
genomically based approaches to metabolic engineering, strain design, and
development.
PMID- 10191387
TI - Multiple mechanisms controlling carbon metabolism in bacteria.
AB - Catabolite repression is a universal phenomenon, found in virtually all living
organisms. These organisms range from the simplest bacteria to higher fungi,
plants, and animals. A mechanism involving cyclic AMP and its receptor protein
(CRP) in Escherichia coli was established years ago, and this mechanism has been
assumed by many to serve as the prototype for catabolite repression in all
organisms. However, recent studies have shown that this mechanism is restricted
to enteric bacteria and their close relatives. Cyclic AMP-independent mechanisms
of catabolite repression occur in other bacteria, yeast, plants, and even E.
coli. In fact, single-celled organisms such as E. coli, Bacillus subtilis, and
Saccharomyces cerevisiae exhibit multiple mechanisms of catabolite repression,
and most of these are cyclic AMP-independent. The mechanistic features of the
best of such characterized processes are briefly reviewed, and references are
provided that will allow the reader to delve more deeply into these subjects.
PMID- 10191388
TI - Engineering protein-based machines to emulate key steps of metabolism (biological
energy conversion)
AB - Metabolism is the conversion of available energy sources to those energy forms
required for sustaining and propagating living organisms; this is simply
biological energy conversion. Proteins are the machines of metabolism; they are
the engines of motility and the other machines that interconvert energy forms not
involving motion. Accordingly, metabolic engineering becomes the use of natural
protein-based machines for the good of society. In addition, metabolic
engineering can utilize the principles, whereby proteins function, to design new
protein-based machines to fulfill roles for society that proteins have never been
called upon throughout evolution to fulfill. This article presents arguments for
a universal mechanism whereby proteins perform their diverse energy conversions;
it begins with background information, and then asserts a set of five axioms for
protein folding, assembly, and function and for protein engineering. The key
process is the hydrophobic folding and assembly transition exhibited by properly
balanced amphiphilic protein sequences. The fundamental molecular process is the
competition for hydration between hydrophobic and polar, e.g., charged, residues.
This competition determines Tt, the onset temperature for the hydrophobic folding
and assembly transition, Nhh, the numbers of waters of hydrophobic hydration, and
the pKa of ionizable functions. Reported acid-base titrations and pH dependence
of microwave dielectric relaxation data simultaneously demonstrate the
interdependence of Tt, Nhh and the pKa using a series of microbially prepared
protein-based poly(30mers) with one glutamic acid residue per 30mer and with an
increasing number of more hydrophobic phenylalanine residues replacing valine
residues. Also, reduction of nicotinamides and flavins is shown to lower Tt,
i.e., to increase hydrophobicity. Furthermore, the argument is presented, and
related to an extended Henderson-Hasselbalch equation, wherein reduction of
nicotinamides represents an increase in hydrophobicity and resulting hydrophobic
induced pKa shifts become the basis for understanding a primary energy conversion
(proton transport) process of mitochondria. Copyright 1998 John Wiley & Sons,
Inc.
PMID- 10191389
TI - Artificial promoters for metabolic optimization.
AB - In this article, we review some of the expression systems that are available for
Metabolic Control Analysis and Metabolic Engineering, and examine their
advantages and disadvantages in different contexts. In a recent approach,
artificial promoters for modulating gene expression in micro-organisms were
constructed using synthetic degenerated oligonucleotides. From this work, a
promoter library was obtained for Lactococcus lactis, containing numerous
individual promoters and covering a wide range of promoter activities.
Importantly, the range of promoter activities was covered in small steps of
activity change. Promoter libraries generated by this approach allow for
optimization of gene expression and for experimental control analysis in a wide
range of biological systems by choosing from the promoter library promoters
giving, e.g., 25%, 50%, 200%, and 400% of the normal expression level of the gene
in question. If the relevant variable (e.g., the flux or yield) is then measured
with each of these constructs, then one can calculate the control coefficient and
determine the optimal expression level. One advantage of the method is that the
construct which is found to have the optimal expression level is then, in
principle, ready for use in the industrial fermentation process; another
advantage is that the system can be used to optimize the expression of different
enzymes within the same cell.
PMID- 10191390
TI - Overexpression of a cytosolic chaperone to improve solubility and secretion of a
recombinant IgG protein in insect cells.
AB - The secretion of heterologous IgG proteins in the baculovirus-insect cell
expression system is accompanied by substantial insoluble immunoglobulin in the
infected cells. The accumulation of these insoluble forms suggests a limitation
in the processing and secretory pathway of the infected cells. As a result,
cytosolic hsp70 chaperones, which are known to associate and prevent aggregation
of polypeptides in vitro, have been coexpressed in the infected cells. The hsp70
protein coprecipitated with the immunoglobulin to indicate the formation of a
specific hsp70-immunoglobulin complex in vivo. Immunoblot and pulse chase studies
indicated that coexpression of hsp70 increased intracellular immunoglobulin
solubility. Metabolic labeling experiments revealed that hsp70 increased secreted
immunoglobulin levels after several days infection as compared to infection with
control baculoviruses. Pulse chase studies indicated that hsp70 increases the
solubility of immunoglobulin precursors that are then processed and assembled
into the complete antibody oligomer. A comparison of the action of cytosolic
hsp70 chaperone to the endoplasmic reticulum chaperone BiP suggests sequential
action in which hsp70 increases the solubility of preprocessed immunoglobulin,
while BiP enhances the solubility of processed immunoglobulin chains.
PMID- 10191391
TI - Metabolic engineering of bacteria for ethanol production
AB - Technologies are available which will allow the conversion of lignocellulose into
fuel ethanol using genetically engineered bacteria. Assembling these into a cost
effective process remains a challenge. Our work has focused primarily on the
genetic engineering of enteric bacteria using a portable ethanol production
pathway. Genes encoding Zymomonas mobilis pyruvate decarboxylase and alcohol
dehydrogenase have been integrated into the chromosome of Escherichia coli B to
produce strain KO11 for the fermentation of hemicellulose-derived syrups. This
organism can efficiently ferment all hexose and pentose sugars present in the
polymers of hemicellulose. Klebsiella oxytoca M5A1 has been genetically
engineered in a similar manner to produce strain P2 for ethanol production from
cellulose. This organism has the native ability to ferment cellobiose and
cellotriose, eliminating the need for one class of cellulase enzymes. The optimal
pH for cellulose fermentation with this organism (pH 5.0-5.5) is near that of
fungal cellulases. The general approach for the genetic engineering of new
biocatalysts has been most successful with enteric bacteria thus far. However,
this approach may also prove useful with Gram-positive bacteria which have other
important traits for lignocellulose conversion. Many opportunities remain for
further improvements in the biomass to ethanol processes. These include the
development of enzyme-based systems which eliminate the need for dilute acid
hydrolysis or other pretreatments, improvements in existing pretreatments for
enzymatic hydrolysis, process improvements to increase the effective use of
cellulase and hemicellulase enzymes, improvements in rates of ethanol production,
decreased nutrient costs, increases in ethanol concentrations achieved in biomass
beers, increased resistance of the biocatalysts to lignocellulosic-derived
toxins, etc. To be useful, each of these improvements must result in a decrease
in the cost for ethanol production. Copyright 1998 John Wiley & Sons, Inc.
PMID- 10191392
TI - Genetic manipulation of acid and solvent formation in clostridium acetobutylicum
ATCC 824
AB - The genes coding for enzymes involved in butanol or butyrate formation were
subcloned into a novel Escherichia coli-Clostridium acetobutylicum shuttle vector
constructed from pIMP1 and a chloramphenicol acetyl transferase gene. The
resulting replicative plasmids, referred to as pTHAAD (aldehyde/alcohol
dehydrogenase) and pTHBUT (butyrate operon), were used to complement C.
acetobutylicum mutant strains, in which genes encoding aldehyde/alcohol
dehydrogenase (aad) or butyrate kinase (buk) had been inactivated by
recombination with Emr constructs. Complementation of strain PJC4BK (buk mutant)
with pTHBUT restored butyrate kinase activity and butyrate production during
exponential growth. Complementation of strain PJC4AAD (aad mutant) with pTHAAD
restored NAD(H)-dependent butanol dehydrogenase activity, NAD(H)-dependent
butyraldehyde dehydrogenase activity and butanol production during solventogenic
growth. The development of an alternative selectable marker makes it is possible
to overexpress genes, via replicative plasmids, in mutant strains that lack
specific enzyme activities, thereby expanding the number of possible genetic
manipulations that can be performed in C. acetobutylicum. Copyright 1998 John
Wiley & Sons, Inc.
PMID- 10191393
TI - Metabolic effects of stress mediators on cultured hepatocytes.
AB - Stress mediators play a major role in inducing the hypermetabolic stress state in
the liver after major injuries. The majority of studies on the effect of
mediators on hepatocytes have focused on single factor effects or on the effect
of very complex additives (e. g., serum), and there are no reports which have
rigorously identified specific interactions between stress mediators. We used a
factorial design experimental approach to evaluate the effects of a four to five
day exposure to hormone (glucagon, hydrocortisone, and epinephrine) and cytokine
[tumor necrosis factor-alpha (TNF-alpha) interleukin-1beta (IL-1beta) and
interleukin-6 (IL-6)] stress mediators on stable cultures of rat hepatocytes.
Both individual-factor effects and two factor interactions on the metabolism of
urea, glucose, lactate, ketone bodies, albumin, and fibrinogen were evaluated.
The cultured hepatocyte model exhibited physiologic responses to the applied
stress mediators. While hydrocortisone and epinephrine had no effect, glucagon
induced an increase in glucose and urea synthesis. Interleukin-6 increased
fibrinogen and decreased albumin production. Furthermore, IL-6 and glucagon
caused an increase in the ketone-body ratio (KBR = [acetoacetate]/[beta
hydroxybutyrate]), which is in equilibrium with the intramitochondrial NAD+/NADH.
Tumor necrosis factor-alpha and IL-1beta, on the other hand, decreased the KBR.
An important two-factor interaction between IL-1beta and IL-6 was identified,
namely that IL-1beta effectively negates the positive effect of IL-6 on the KBR
when both are present. These results provide further understanding of the effect
of stress mediators on hepatic function and metabolism. These effects may have
important implications in the pathogenesis of progressive organ dysfunction which
often follows prolonged inflammatory states triggered by major injuries.
PMID- 10191394
TI - Engineering polyphosphate metabolism in Escherichia coli: implications for
bioremediation of inorganic contaminants.
AB - Polyphosphate metabolism plays an important role in the bioremediation of
phosphate contamination in municipal wastewater, and may play a key role in heavy
metal tolerance and bioremediation. However, little is known about the regulation
of polyphosphate metabolism in microorganisms and its role in heavy metal
toxicity. We have manipulated polyphosphate metabolism in Escherichia coli by
overexpressing the genes for polyphosphate kinase (ppk) and for polyphosphatase
(ppx) under control of their native promoters and inducible promoters.
Overexpression of ppk results in high levels of intracellular polyphosphate,
improved phosphate uptake, but no increase in tolerance to heavy metals.
Overexpression of both ppk and ppx results in lower levels of intracellular
polyphosphate, secretion of phosphate from the cell, and increased tolerance to
heavy metals. Metabolic flux analysis indicates that the cell responds to
increased flux through the PPK-PPX pathway by altering flux through the TCA
cycle.
PMID- 10191395
TI - Rational engineering of the TOL meta-cleavage pathway
AB - The meta-cleavage pathway of Pseudomonas putida mt-2 was simulated using a
biochemical systems simulation developed by Regan (1996). A non-competitive
inhibition term for catechol-2,3-dioxygenase (C23O) by 2-OH-pent-2,4-dienoate (Ki
= 150 MUM) was incorporated into the model. The simulation predicted steady state
accumulation levels in the MUM range for metabolites pre-meta-cleavage, and in
the mM range for metabolites post-meta-cleavage. The logarithmic gains L[V-i, Xj]
and L[X-i, Xj] clearly indicated that the pathway was most sensitive to the
concentration of the starting substrate, benzoate, and the first enzyme of the
pathway, toluate-1, 2-dioxygenase (TO). The simulation was validated
experimentally; it was found that the amplification of TO increased the steady
state flux from 0.024 to 0.091 (mmol/g cell dwt)/h. This resulted in an increased
accumulation of a number of the pathway metabolites (intra- and extracellularly),
especially cis-diol, 4-OH-2-oxovalerate, and 4-oxalocrotonate. Metabolic control
analysis indicated that C23O was, in fact, the major controling enzymic step of
the pathway with a scaled control coefficient of 0.83. The amplification of TO
resulted in a shift of some of the control away from C23O. Catechol-2,3
dioxygenase, however, remained as the major controling element of the pathway.
Copyright 1998 John Wiley & Sons, Inc.
PMID- 10191396
TI - In vivo 13C-NMR studies of polymer synthesis in rhizobium meliloti M5N1 strain
AB - The use of in vivo 13C-NMR approach for the monitoring of the synthesis of
various polymers within cells of Rhizobium meliloti (M5N1 strain) is reported.
Significant differences in polymer biosynthesis have been shown as a function of
the metabolic state of the cells and the labeled carbon source used. Consumption
of carbon source and produced glycogen was complete with mid-exponential phase
harvested cells. This was not the case with stationary phase harvested cells, for
which polyhydroxybutyrate synthesis was higher and gluconate synthesis was lower
than the former. [1-13C]fructose-grown cells produced more exopolysaccharide and
polyhydroxybutyrate, but less beta-(1,2) glucan and gluconate than [1-13C]glucose
grown cells. This approach offers a suitable tool to examine the kinetics of
polymer biosynthesis by Rhizobia. Copyright 1998 John Wiley & Sons, Inc.
PMID- 10191397
TI - 13C tracer experiments and metabolite balancing for metabolic flux analysis:
comparing two approaches
AB - Conventional metabolic flux analysis uses the information gained from
determination of measurable fluxes and a steady-state assumption for
intracellular metabolites to calculate the metabolic fluxes in a given metabolic
network. The determination of intracellular fluxes depends heavily on the
correctness of the assumed stoichiometry including the presence of all reactions
with a noticeable impact on the model metabolite balances. Determination of
fluxes in complex metabolic networks often requires the inclusion of NADH and
NADPH balances, which are subject to controversial debate. Transhydrogenation
reactions that transfer reduction equivalents from NADH to NADPH or vice versa
can usually not be included in the stoichiometric model, because they result in
singularities in the stoichiometric matrix. However, it is the NADPH balance
that, to a large extent, determines the calculated flux through the pentose
phosphate pathway. Hence, wrong assumptions on the presence or activity of
transhydrogenation reactions will result in wrong estimations of the
intracellular flux distribution. Using 13C tracer experiments and NMR analysis,
flux analysis can be performed on the basis of only well established
stoichiometric equations and measurements of the labeling state of intracellular
metabolites. Neither NADH/NADPH balancing nor assumptions on energy yields need
to be included to determine the intracellular fluxes. Because metabolite
balancing methods and the use of 13C labeling measurements are two different
approaches to the determination of intracellular fluxes, both methods can be used
to verify each other or to discuss the origin and significance of deviations in
the results. Flux analysis based entirely on metabolite balancing and flux
analysis, including labeling information, have been performed independently for a
wild-type strain of Aspergillus oryzae producing alpha-amylase. Two different
nitrogen sources, NH4+ and NO3-, have been used to investigate the influence of
the NADPH requirements on the intracellular flux distribution. The two different
approaches to the calculation of fluxes are compared and deviations in the
results are discussed. Copyright 1998 John Wiley & Sons, Inc.
PMID- 10191398
TI - Metabolite-balancing techniques vs. 13C tracer experiments to determine metabolic
fluxes in hybridoma cells.
AB - The estimation of intracellular fluxes of mammalian cells using only mass
balances of the relevant metabolites is not possible because the set of linear
equations defined by these mass balances is underdetermined. In order to quantify
fluxes in cyclic pathways the mass balance equations can be complemented with
several constraints: (1) the mass balances of co-metabolites, such as ATP or
NAD(P)H, (2) linear objective functions, (3) flux data obtained by isotopic
tracer experiments. Here, these three methods are compared for the analysis of
fluxes in the primary metabolism of continuously cultured hybridoma cells. The
significance of different theoretical constraints and different objective
functions is discussed after comparing their resulting flux distributions to the
fluxes determined using 13CO2 and 13C-lactate measurements of 1 - 13C-glucose-fed
hybridoma cells. Metabolic fluxes estimated using the objective functions
"maximize ATP" and "maximize NADH" are relatively similar to the experimentally
determined fluxes. This is consistent with the observation that cancer cells,
such as hybridomas, are metabolically hyperactive, and produce ATP and NADH
regardless of the need for these cofactors.
PMID- 10191399
TI - A simple structured model describing the growth of Streptomyces lividans.
AB - The growth of Streptomyces lividans in defined media was modeled using a simple
structured growth model. Conventional unstructured models like Monod kinetics,
substrate inhibition kinetics, and the logistic equation were also used in an
attempt to fit the data, but the results were all unsatisfactory. The main reason
for failure in applying simple unstructured models is that they cannot describe
the long lag phases sometimes observed during growth of S. lividans. The simple
structured growth model was derived along similar principles to cybernetic growth
models. This model quite accurately describes the growth of S. lividans. It
assumes that the rate of assimilation of a substrate depends on the concentration
of a specific key enzyme. This key enzyme is only produced in the presence of the
substrate, and it is broken down at a steady rate. An enzyme synthesis allocation
variable, w, similar to the cybernetic variable, u, described in cybernetic
growth models, is proposed to control enzyme synthesis. Until the key enzyme
concentration approaches its maximum level, very little substrate is consumed.
And consequently, the lag phase is sustained.
PMID- 10191400
TI - Redesigning metabolic networks using mathematical programming
AB - The design of new generation bioprocessing plants is increasingly dependent on
the design of process-compatible microorganisms. The latter, whether through
genetic or physiological manipulations, can be greatly assisted by metabolic
engineering. An emerging powerful tool in metabolic engineering research is
computer-assisted cell design using mathematical programming. In this work, the
problem of optimizing cellular metabolic networks has been formulated as a Mixed
Integer Nonlinear Programming (MINLP) model. The model can assist genetic
engineers to identify which cellular enzymes should be modified, and the new
levels of activity required to produce an optimal network. Results are presented
from the tricarboxylic acid cycle in Dictyostelium discoideum. Copyright 1998
John Wiley & Sons, Inc.
PMID- 10191401
TI - Cell cycle dependence of retroviral transduction: An issue of overlapping time
scales.
AB - Recombinant retroviruses are currently used as gene delivery vehicles for the
purpose of gene therapy. It is generally believed that the efficiency of
retroviral transduction depends on the cell cycle status of the target cells.
However, it has been reported that this is not the case for the transduction of
human and murine fibroblasts, in contrast to other cell types such as
lymphocytes. The predictions of a mathematical model that we constructed, offer
an explanation of this contradiction, based on the dynamics of the underlying
processes of target cell growth and the intracellular decay of retroviral
vectors. The model suggests that the utility of synchronization experiments, that
are usually employed to study cell cycle specificity, is severely limited when
the time scales of the above kinetic events are comparable to each other. The
predictions of the model also suggest the use of retroviral vectors as cell cycle
markers, as an alternative way to detect cell cycle dependence of retroviral
transduction. This method obviates the need for cell synchronization and
therefore, it does not perturb the cell cycle or interfere with the life cycle of
retroviral vectors. Moreover, it does not depend on the intracellular stability
of retroviral vectors. Our results show that in contrast to previously reported
results, transduction of murine fibroblasts is cell cycle dependent, and they are
consistent with the current notion that mitosis is the phase that confers
transduction susceptibility.
PMID- 10191402
TI - Application of cybernetic models to metabolic engineering: investigation of
storage pathways
AB - A cybernetic model is proposed to examine generic features of storage pathways.
This model is capable of describing synthesis of carbon and non-carbon storage
polymers. The effect of environmental conditions is evaluated using storage
polymer level as a fraction of total biomass as a gauge of pathway performance.
The base wild-type pathway is then analyzed to determine the effect of genetic
alterations upon system performance. Proposed modifications are tested using the
cybernetic model as a diagnostic tool to ascertain the ramifications of potential
genetic alterations. A methodology is developed within the cybernetic framework
to describe alterations of enzyme activity and over-expression of pathway
enzymes. Copyright 1998 John Wiley & Sons, Inc.
PMID- 10191403
TI - Stimulation of glucose catabolism through the pentose pathway by the absence of
the two pyruvate kinase isoenzymes in Escherichia coli.
AB - Escherichia coli strains devoid of one or both of the two pyruvate kinase
isoenzymes (PKA and PKF), were grown on minimal media in batch fermentations. The
strain lacking both PKs showed a 28% decrease on its specific growth rate when
compared to the wild type. However, protein and CO2 yields did not change. Using
radioactive 1-C14 glucose and collecting the CO2 produced by the cultures, it was
found that the mutant lacking both pyruvate kinases, metabolized glucose mainly
through the pentose pathway (PP). The increased participation of the PP in
glucose metabolism in this strain, was also reflected on the levels of the
glucose-6-phosphate and 6-phosphogluconate dehydrogenases.
PMID- 10191404
TI - Rational design of an improved induction scheme for recombinant Escherichia coli.
AB - In Escherichia coli, strong overexpression of a recombinant protein has been
shown to be deleterious due to a heavy metabolic burden on the host cell, which
may completely cease cell growth before maximum product accumulation has
occurred. Aiming at a reduction of very high product formation rates, we
engineered E. coli strains by mutating the Leloir pathway for galactose
metabolization, so that galactose can be utilized to induce lac derived
promoters. The induction with galactose was effective in every strain and
expression construct tested, and it reduced the metabolic burden on a highly
overproducing clone so that cell growth and product accumulation could be
maintained for several generations.
PMID- 10191405
TI - An experimental study on carbon flow in Escherichia coli as a function of kinetic
properties and expression levels of the enzyme phosphoglucomutase.
AB - Mutants of Escherichia coli deficient in phosphoglucomutase accumulate amylose
when the cells are grown on maltose or galactose as carbon source. In the
presence of physiological levels of phosphoglucomutase, most of the sugar is
catabolized, leading to strongly reduced levels of amylose accumulation. By
varying the expression level of heterologous phosphoglucomutase, we show that the
minimum level needed to block amylose accumulation corresponds to a
phosphoglucomutase activity of 150-600 nmole substrate transformed per min per mg
of total soluble protein. Mutant phosphoglucomutases with strongly reduced Vmax
values and increased Km values for the substrate glucose-1-phosphate or the co
substrate glucose-1,6-diphosphate, could also reduce amylose accumulation, but
much higher enzyme expression levels were required.
PMID- 10191406
TI - Uncoupled glycerol distribution as the origin of the accumulation of 3
hydroxypropionaldehyde during the fermentation of glycerol by enterobacter
agglomerans CNCM 1210
AB - Batch fermentation of glycerol to 1,3-propanediol (1,3PPD) by Enterobacter
agglomerans CNCM 1210 showed the lethal accumulation of 3-hydroxypropionaldehyde
(3-HPA) when performed under initial substrate content higher than 40 g/L.
Assigned to the inhibition by the NAD/NADH ratio of the 3-HPA converting enzyme:
1,3PPD dehydrogenase, intracellular assays were conducted in an attempt to
identify the metabolic mechanisms involved in the increase of that ratio. An
overflow metabolism through the 1,3PPD formation pathway was established, while a
catabolic limitation in the oxidative branch at the level of glyceraldehyde-3
phosphate dehydrogenase occurred. Uncoupled activities of synthesis and
consumption of reducing equivalents are thus suspected to provoke the increase of
the NAD/NADH ratio and the subsequent accumulation of 3-HPA. Copyright 1998 John
Wiley & Sons, Inc.
PMID- 10191407
TI - Production of lycopene by the food yeast, Candida utilis that does not naturally
synthesize carotenoid.
AB - The Erwinia uredovora crtE, crtB, and crtI genes, which are responsible for the
synthesis of carotenoid lycopene from farnesyl pyrophosphate, were expressed in
Candida utilis under the control of the promoters and terminators derived from
the C. utilis GAP, PGK, and PMA genes, respectively. The yeast transformant
carrying the carotenoid biosynthesis genes produced 758 microg/g dry weight of
lycopene along with 407 microg/g dry weight of phytoene in the stationary phase.
It was observed in the C. utilis transformant that ergosterol content was
decreased to 65% of that in the parent strain that accumulated 6.04 mg/g dry
weight of ergosterol. It is therefore possible that the carbon flux for the
ergosterol biosynthesis has been branched at farnesyl pyrophosphate to generate a
new pathway for the lycopene production in this yeast transformant.
PMID- 10191408
TI - Direct fermentation of 2-keto-L-gulonic acid in recombinant Gluconobacter
oxydans.
AB - We isolated Gluconobacter oxydans T-100 that had an activity to produce 2-KLGA
from D-sorbitol; however, the yield of 2-KLGA was quite insufficient. Therefore,
enzymes involved in the biosynthesis of L-sorbosone and 2-KLGA, L-sorbose
dehydrogenase (SDH) and L-sorbosone dehydrogenase (SNDH), respectively, were
purified from G. oxydans T-100. A genomic library of G. oxydans T-100 was
screened to clone both genes for SDH and SNDH based on their amino acid
sequences. SNDH and SDH were encoded in sequential open reading frames with 1497
and 1596 nucleotides, respectively, which were verified by the expression in
Escherichia coli. The amino acid sequence of SDH and SNDH showed close similarity
with E. coli choline dehydrogenase (CDH) and betaine-aldehyde dehydrogenase
(BADH), respectively, which cooperatively play a key role for conferring osmotic
tolerance. Because the yield of 2-KLGA by G. oxydans introduced with the genes
for SDH and SNDH were insufficient, replacement of the promoter with that of
Escherichia coli tufB1 in combination with chemical mutagenesis by N-methyl-N'
nitro-N-nitrosoguanidine resulted in improvement of the production level.
PMID- 10191409
TI - Allocation of ATP to synthesis of cells and hydrolytic enzymes in cellulolytic
fermentative microorganisms: bioenergetics, kinetics, and bioprocessing.
AB - Under anaerobic, carbon limited conditions, celluloytic fermentative
microorganisms face a metabolic choice with respect to the allocation of
relatively scarce ATP: to invest it in cells or in hydrolytic enzymes. A model is
proposed that defines an allocation parameter reflecting the fractional
expenditure of ATP on cell synthesis relative to the total ATP available (gross
ATP synthesized less maintenance). This parameter is then incorporated into an
ATP-centered model of anaerobic cellulose fermentation based on the ethanol
fermentation of yeast and the cellulase system of Trichoderma reesei. Results
indicate that high processing rates are possible via a consolidated bioprocessing
strategy, especially at high cellulase specific activities, and that
cell/cellulase allocation represents an interesting system in which to study, and
perhaps exploit, microbial evolution and metabolic control.
PMID- 10191410
TI - Yeast cell permeabilizing beta-1,3-glucanases: A tool for the integration of
downstream processes and metabolic engineering applications to yeast.
AB - In this article, we consider the impact on downstream process design resulting
from the use of metabolically engineered yeast strains. We address the issue of
how manipulation of cell wall permeability can improve the release and subsequent
recovery of heterologous products produced in yeast.
PMID- 10191411
TI - High cell density culture of metabolically engineered Escherichia coli for the
production of poly(3-hydroxybutyrate) in a defined medium.
AB - A recombinant Escherichia coli strain XL1-Blue harboring a stable high-copy
number plasmid pSYL107 containing the Alcaligenes eutrophus polyhydroxyalkanoate
biosynthesis genes and the Escherichia coli ftsZ gene was employed for the
production of poly(3-hydroxybutyrate) (PHB) by fed-batch culture in a defined
medium. Suppression of filamentation by overexpressing the cell division protein
FtsZ allowed production of PHB to a high concentration (77 g/L) with high
productivity (2 g/L/h) in a defined medium, which was not possible with the
recombinant E. coli that underwent filamentation. Further optimization of fed
batch culture condition resulted in PHB concentration of 104 g/L in a defined
medium, which was the highest value reported to date by employing recombinant E.
coli.
PMID- 10191413
TI - Quantification of metabolites in the indole alkaloid pathways of catharanthus
roseus: implications for metabolic engineering
AB - In this article, we present a review of the current state of metabolic
engineering in Catharanthus roseus. A significant amount of research has
contributed to characterization of several individual steps in the biosynthetic
pathway of medicinally valuable alkaloids. However, knowledge of the regulation
of these pathways is still sparse. Using hairy root cultures, we studied the
responses of alkaloid metabolism to environmental stimulation such as light and
elicitation. Through precursor feeding studies, the putative rate-limiting steps
of the terpenoid pathway in hairy root cultures also have been examined. Relating
this knowledge to specific events at the molecular level, and the cloning of
corresponding genes are the next key steps in metabolic engineering of the C.
roseus alkaloids. Copyright 1998 John Wiley & Sons, Inc.
PMID- 10191412
TI - Metabolic engineering of cultured tobacco cells.
AB - Construction of a gene expression system in tobacco cultured cells (BY2) was
studied. A 925 bp promoter fragment of a heat-shock protein gene (HSP18.2) of
Arabidopsis thaliana showed clear heat-shock response of expression of the beta
glucuronidase (GUS) reporter gene in BY2 cells. Similar results were observed in
a 500 mL flask and 3-L jar fermentor. Isolation of strong promoters in BY2 cells
was tried. cDNA clones, in which the mRNA level is high in log-phase cells and
the copy number in the genome is low, were isolated. These clones showed high
homology with F1-ATPase (mitochondria type), elongation factor 1-alpha, and a
gene with an unknown function of A. thaliana (clone 27), respectively. A 5'
flanking region of clone 27 showed 6.2 times the promoter activity of the CaMV35S
promoter in BY2 cells. Three cDNA clones, which are expressed in the stationary
growth phase of BY2 cells, were isolated by a differential screening. These
clones showed high sequence homologies to alcohol dehydrogenase, pectin esterase,
and extensin. Promoters of these genes will be useful in gene expression in high
cell-density culture.
PMID- 10191414
TI - Production of L-DOPA(3,4-dihydroxyphenyl-L-alanine) from benzene by using a
hybrid pathway.
AB - As an alternative approach to the production of L-DOPA from a cheap raw material,
we constructed a hybrid pathway consisting of toluene dioxygenase, toluene cis
glycol dehydrogenase, and tyrosine phenol-lyase. In this pathway, catechol is
formed from benzene through the sequential action of toluene dioxygenase and
toluene cis-glycol dehydrogenase, and L-DOPA is synthesized from the resulting
catechol in the presence of pyruvate and ammonia by tyrosine phenol-lyase cloned
from Citrobacter freundii. When the hybrid pathway was expressed in E. coli,
production of L-DOPA was as low as 3 mM in 4 h due to the toxic effect of benzene
on the cells. In order to reduce lysis of cells, Pseudomonas aeruginosa was
employed as an alternative, which resulted in accumulation of about 14 mM L-DOPA
in 9 h, showing a stronger resistance to benzene.
PMID- 10191415
TI - CCR5 genotype and human immunodeficiency virus (HIV)-specific mucosal antibody in
seronegative women at high risk for HIV infection.
PMID- 10191416
TI - Spontaneous ultraweak bioluminescence in plants: origin, mechanisms and
properties.
AB - An analysis of theoretical knowledge and experimental results of ultraweak
luminescence (UWL) is provided. The role of excited state of molecules and free
radicals, formed in various biochemical reactions, in UWL is discussed. UWL of
model reactions and in vivo systems are compared. The hypothesis of coherent
electromagnetic field as a source of UWL is also discussed. Spectral, kinetic and
temporal properties of UWL are summarised, as well as their connection with its
origin and role in the organism. Attention is paid to recent progress in
experimental methods of low-light detection. The possible use of UWL in
environmental studies, selection and other applications is discussed.
PMID- 10191417
TI - Mannitol derivate used as a marker for voltammetrically monitored transport
across the blood-brain barrier under condition of locus coeruleus stimulation.
AB - 1-Deoxy-1-nitro-D-mannitol (DN-Man) was used (femoral vein injection, approximate
concentration in the blood 30 mmol.l-1) in pentobarbital anaesthetized rats as a
promising marker detectable by differential pulse voltammetry (DPV) to study its
transport across the blood-brain barrier (BBB) to the extra-cellular space of the
frontoparietal cortex. DN-Man detection limit in in vitro calibrations (saline,
blood) using DPV and carbon fiber microelectrodes was 0.5 mmol.l-1 with a good
linearity (r = = 0.996) over the entire tested range (up to 30 mmol.l-1). The
slow time-course of the rise of DN-Man signal (y = 106/(1 + (17.8/t)3)) in the
cortex confirmed the functional BBB state. Electrical stimulation of the locus
coeruleus (LC) (300 rectangular pulses at a frequency of 100 Hz, 1 mA, pulse
duration 0.2 ms) elevated significantly DN-Man current in the cortex (to 168 +/-
59% of the control, mean +/- S.D., n = 8). The evoked permeation increase of the
BBB to DN-Man was short-lasting (minutes), and the second LC stimulation
(repeated 5 min after the first one) was ineffective. This fact was probably due
to the reduction of DN-Man levels in blood and/or an altered response of
microvessels to neurotransmitters. It was shown here that, under carefully
controlled surgical and experimental conditions, DPV and DN-Man might be useful
for the monitoring of the regional dynamics of BBB transport changes. The
presented results also support the view that BBB transport can be influenced by
LC neuronal activity.
PMID- 10191418
TI - The binding problem in population neurodynamics: a network model for stimulus
specific coherent oscillations.
AB - A hypothesis is presented that coherent oscillatory discharges of spatially
distributed neuronal groups (the supposed binding mechanism) are the result of
the convergence of stimulus-dependent activity in modality-specific afferent
pathways with oscillatory activity generated in unspecific sensory systems. This
view is supported by simulation experiments on model networks.
PMID- 10191419
TI - Adjuvant arthritis in the rat is associated with decreased binding of nuclear
receptors to thyroid hormone responsive element in spleen extracts.
AB - In vertebrates, thyroid hormone and its cognate nuclear receptors are involved in
a complex arrangement of physiological and developmental function. Since thyroid
hormone has also been shown to affect immune responses, we investigated the DNA
binding status of T3 receptors of spleen nuclear extracts in a) rats with
adjuvant arthritis (AA); b) adrenalectomized rats (ADX), and c) animals with
adjuvant arthritis followed by adrenalectomy (AA + ADX). A marked diminution in
the functional binding of nuclear thyroid hormone receptors to DR4 thyroid
hormone responsive DNA element was found in the spleens of AA and AA + ADX rats
when compared to a control group or ADX rats. The data based on in vivo
experiments suggest that the nuclear receptor--thyroid hormone responsive element
complex status within the cell nucleus may be altered in adjuvant arthritis.
PMID- 10191420
TI - Channel-sizing experiments in multichannel bilayers.
AB - The possibility of obtaining information about the radius of high and low
conductance states of channels in multichannel membranes was tested
experimentally. In spite of the interference of non-electrolytes on the numbers
of channels that appeared in the membrane, the non-electrolyte-exclusion method
was successfully adapted to multichannel bilayers to estimate the radius of the
larger opening of the low conductance state of the channel induced by
Staphylococcus aureus alpha-toxin. At the pH used, the channel transition to a
low conductance state was accompanied by a decrease of the opening radius from
1.3 +/- 0.2 nm to 0.9 +/- 0.1 nm. The determination criteria for maximum size of
a channel opening when using the non-electrolyte exclusion method is discussed.
PMID- 10191421
TI - Low-power laser irradiation induces leukocyte priming.
AB - Laser radiation (LR) of various spectral composition has been broadly used in
clinical practice. However, the mechanism of the stimulating effects of LR
remains obscure. The effect of He-Ne LR (633 nm) on human blood leukocytes was
investigated both in the absence and presence of 8.65 nmol/l phthalocyanine
(PhC). Irradiation of non-stimulated leukocytes with 0.025 to 0.5 J/cm2 did not
lead to any activation of their luminol-dependent chemiluminescence (LCL). On the
other hand, LR increased in most cases the subsequent CL response of the cells to
opsonized zymosan (priming action of He-Ne-laser light). The effect of LR on the
leukocytes was not standard. In irradiated leukocytes isolated from patients with
severe acute or chronic pneumonia, or chronic bronchitis, the maximal LCL
exceeded that for non-irradiated cells by 80% (0.05 J/cm2), 20-25% (0.15 J/cm2),
and 0%, respectively (doses are shown in parentheses). Further increase of the
exposure brought about a dose-dependent inhibition of LCL in cells from patients
with severe acute and chronic pneumonia. There was an intriguing relationship
between maximal CL responses of leukocytes subjected to laser irradiation in the
presence and without PhC. When the priming effect of LR on isolated cells was
small, it increased in the presence of exogenous photosensitizer, phthalocyanine;
in cells of severely ill patients where the initial effect of LR was strong, Pc
inhibited the priming action of LR. Apparently, different cells contained
different amounts of endogenous photosensitizer(s); the addition of exogenous
sensitizer increased the priming action of LR at low concentrations and decreased
it at higher concentrations of the endogenous photosensitizer.
PMID- 10191422
TI - Pulmonary xanthine oxidase activity of rats exposed to prolonged immobilization
stress.
AB - This study was designed to study xanthine oxidase (XO) and xanthine dehydrogenase
(XD) activity in the lung of rats exposed to prolonged restraining immobilization
stress. Immobilization caused more than twofold increase of xanthine oxidase
activity in the rat lung. The activity of xanthine oxidase decreased in lung
homogenates incubated at -20 degrees C for 24 h. The same incubation of
homogenates from control rats caused a non-significant increase of the activity.
No measurable NAD(+)-dependent xanthine dehydrogenase activity could be
established in the lungs of both control rats and rats subjected to
immobilization. All rats revealed methylene blue-dependent xanthine dehydrogenase
activity which was more than two-times higher in the immobilized animals.
Incubation at -20 degrees C for 24 h increased the methylene blue-dependent
xanthine dehydrogenase activity in homogenates from control rats and decreased
the enzyme activity in homogenates from immobilized rats. A working hypothesis
was proposed for the sequence of events explaining the results obtained: XO
catalyzed generation of activated oxygen species may take place in the initiation
of lipid peroxidation in the lung of rats immobilized for prolonged periods of
time.
PMID- 10191423
TI - Modulation of mitochondrial contact sites formation in immature rat heart.
AB - Creatine phosphokinase-mediated transport of energy from the site of production
to the site of consumption is a key process for meeting the energy-demands of
reactions in cytosol. The mitochondrial creatine phosphokinase (mCPK) plays an
important role in this process, with the enzyme activity localized particularly
in the mitochondrial contact sites (MiCS). Earlier studies in adult animals have
shown that the formation of MiCS varies in response to the energy demand and the
physiological state of the heart, and it is stimulated by an increase in [Ca2+]i.
However, there is little known about MiCS formation in juvenile hearts,
characterized by metabolism different from adult hearts. In the present study we
investigated the modulation of MiCS formation via Ca2+ in hearts of 14-day-old
rats. The moderate response of MiCS to various stimuli (elevated extracellular
Ca2+, diltiazem, cardiac arrest by Cd2+) may refer to a still increased
intracellular Ca2+ concentration, the incomplete development of mitochondrial
energy production as well as to persistingly high energy demand of the developing
heart.
PMID- 10191424
TI - Presenting symptoms and clinical features in 130 patients with the velo-cardio
facial syndrome. The Leuven experience.
AB - During the last 5 years, we diagnosed in Leuven 130 patients with a 22q11
deletion. The deletion was familial in 14 out of 110 index patients (12%), which
is significantly less compared to previous studies. In 10 patients, the deletion
was maternal, in 4 patients paternal. A cardiac defect was the main presenting
symptom in 49% of patients. The other patients were ascertained through
developmental delay (16%), behavioural disturbances (7%), otorhinolaryngological
manifestations (6%), psychiatric manifestations (3%) and mental retardation (2%).
In one patient hypocalcemia was the presenting symptom. In another patient the
severe immune deficiency led to diagnosis. Most patients presented a wide variety
of the classical features of the Velo-Cardio-Facial syndrome. Velopharyngeal
incompetence, learning difficulties or mostly mild mental retardation were almost
always present, whereas clinical significant hypocalcemia or immune disturbances
were rare. Previously un(der)recognised features include polyhydramnios, renal
malformations and laryngotracheamalacia or laryngeal stenosis.
PMID- 10191425
TI - The Philadelphia story: the 22q11.2 deletion: report on 250 patients.
AB - A submicroscopic deletion of chromosome 22q11.2 has been identified in the
majority of patients with the DiGeorge, velocardiofacial, and conotruncal anomaly
face syndromes, and in some patients with the Opitz G/BBB and Cayler cardiofacial
syndromes. We have been involved in the analysis of DiGeorge syndrome and related
diagnoses since 1982 and have evaluated a large number of patients with the
deletion. We describe our cohort of 250 patients whose clinical findings help to
define the extremely variable phenotype associated with the 22q11.2 deletion and
may assist clinicians in providing genetic counseling and guidelines for clinical
management based on these findings.
PMID- 10191426
TI - Congenital heart defects in patients with DiGeorge/velocardiofacial syndrome and
del22q11.
AB - Congenital heart defects (CHDs) are found in 75% of patients with
DiGeorge/velocardiofacial (DG/VCF) syndromes with deletion 22q11.2 (del22q11).
The purpose of this study was to analyse clinical features and, particularly,
types and subtypes of CHDs associated with del22q11 in our series of patients and
in those reported in other studies. All patients with CHD and del22q11 present
major or minor clinical features of DG/VCF syndrome. Many children, particularly
in the neonatal age, have only a "subtle" phenotype, so that accurate
phenotypical evaluation is mandatory for selecting patients with CHD at risk for
del22q11. Conotruncal cardiac defects are the most common CHDs in patients with
DG/VCF syndrome, but other defects can also occur. Peculiar anatomical subtypes
are found in patients with del22q11. They are frequently complex, consisting in
malalignment with deficiency of the infundibular septum and anomalies of the
aortic arch and pulmonary arteries.
PMID- 10191427
TI - Chromosome 22q11 deletions in patients with selected outflow tract malformations.
AB - The incidence of 22q11 deletions and its effect on the phenotype were established
in 170 patients with selected outflow tract malformations and transposition of
the great arteries (conotruncal defects). Cases were seen both prospectively and
retrospectively. All patients had a dysmorphological evaluation by the clinical
geneticist and a cytogenetic analysis including FISH analysis for 22q11
deletions. A chromosomal abnormality was present in 29 patients, including a
22q11 deletion in 22/170 patients (13%). The 22q11 deletion was found in 11% of
tetralogy of Fallot, in 11% of pulmonary atresia and VSD, in 44% of pulmonary
atresia. VSD and collateral arteries, in 20% of truncus arteriosus, in 60% of
interrupted aortic arch and in 25% patients with aberrant subclavian artery. They
were absent in double outlet right ventricle or in transposition of the great
arteries. No parental deletion was found. All patients had clinical
characteristics of the velocardiofacial syndrome. This study confirms a high
incidence of chromosome 22q11 deletions in patients with selected outflow tract
malformations, with great clinical impact for further management and genetic
counseling.
PMID- 10191428
TI - 22q11 deletion in DGS/VCFS monozygotic twins with discordant phenotypes.
AB - 22q11.2 deletion is a common genetic disorder characterised by a wide spectrum of
clinical manifestations. To date no simple genotype-phenotype correlation has
been established. Moreover, several reports have mentioned phenotypic discordance
between monozygotic twins. No definite mechanism has been demonstrated and
mosaicism, a postzygotic second hit, environmental effects and chance events have
been proposed. The twinning process itself has been suspected in two cases (11,
23). We report the case of monozygous twins with a 22q11.2 deletion who are
discordant for a heart defect. We found no arguments for mosaicism or twin-to
twin transfusion syndrome. The frequent discordance for heart defects in
DiGeorge/Velo-cardio-facial syndromes (DGS/VCFS) does not favour the hypothesis
of somatic mutations contributing to the phenotypic variation, but rather a
complex interaction between genetic and environmental systems.
PMID- 10191429
TI - The deletions of 22q11--the Portuguese experience.
AB - The patients with a chromosome 22q11 deletion have a variable phenotype which
includes DiGeorge (DG) and Velocardiofacial (VCF) syndromes. The aim of the
present study is to characterize the phenotype of DG and VCF using facial
biometry in 12 portuguese patients. We found 4/12 patients with the DG phenotype:
3/4 had telecanthus, small mouth and retrognathia; 1/4 had telecanthus, short
nose with bulbous tip and a normal mouth. These patients had major cardiac
defects associated with hypoplastic or absent thymus and monosomy 22q11. We did
not find velopharyngeal insufficiency in patients with the so called DG phenotype
8/12 patients had the VCF phenotype: typical facies with variable features. Four
of these had velopharyngeal insufficiency and learning disabilities. Four
patients had cardiac defects and 5/8 had monosomy 22q11. Probably this clinical
variability is due to mutations in critical genes involved in embryonic
development.
PMID- 10191430
TI - The phenotypic spectrum of the 10p deletion syndrome versus the classical
DiGeorge syndrome.
AB - We reviewed 36 patients with a deletion of the short arm of chromosome 10 and a
partial DiGeorge syndrome. We compared the phenotypes observed in these del(10p)
patients with the classical DiGeorge phenotype associated with del(22q11),
pointing out both similarities and differences. Some features, such as
sensorineural hearing loss, seem to be highly associated with a deletion of 10p
but are absent in the classical DiGeorge spectrum caused by del(22q11).
PMID- 10191431
TI - Abdominal lymphatic dysplasia and 22q11 microdeletion.
AB - We report the case of a child with 22q11 microdeletion who presented with
abdominal lymphatic dysplasia resulting in exsudative enteropathy. This primitive
and localized lymphatic malformation is consistent with the vascular theory in
the velocardiofacial syndrome.
PMID- 10191432
TI - Retrospective analysis of feeding and speech disorders in 50 patients with velo
cardio-facial syndrome.
AB - We report data on feeding and speech disorders in 50 patients with
velocardiofacial syndrome. In order to contribute to delineation of type and
etiology of feeding and speech problems, we compared the clinical findings in
these patients with the reports in literature.
PMID- 10191433
TI - The behavioural phenotype in velo-cardio-facial syndrome (VCFS): from infancy to
adolescence.
AB - In this contribution the current status and recent findings of the behavioural
phenotype in VCFS (22q11 deletion) are discussed with regard to motor
development, cognition and neurodevelopment, and behaviour and temperament.
Motor: hypotonia in infancy, gross-motor milestones are delayed, problems with
coordination and balance from preschool age on, problems with tempo/speed during
adolescence. Cognition and neurodevelopment: learning disabilities (82-100%),
intellectual disability (45%), better verbal abilities than performal abilities,
poor attention and concentration, visuo-perceptual-spatia problems, good
(auditory) memory. An important subgroup of children (55%) has a non-verbal
learning disability (NLD). Behaviour and social-emotional development AD(H)D,
withdrawn and shy, person-dependent social problems in relationships with peers,
anxious, risk for child psychiatric problems as well as for the development of
psychiatric problems during adolescence and early adulthood. Information on the
behavioural phenotype in VCFS (22q11 deletion) is of great importance to
clinicians as an aid to syndrome diagnosis, but even more to parents because it
offers immense direct practical value to the management of the behaviour of their
child. Appropriate counseling and information on the long-term expectations, and
better insight in the behaviour will lead to the development of realistic ways of
coping with their child.
PMID- 10191434
TI - Behavior problems and personality aspects of 40 children with velo-cardio-facial
syndrome.
AB - Data are collected with the Child Behavior Check List (CBCL) as well as with the
Teacher Report Form (TRF) of 40 VCFS children between 4 and 18 years of age. Half
of the group shows very high problem scores in the "clinical" range. The average
T-score of the VCFS children as a group are over 60 (one standard deviation above
the mean) for the "total problem score" and the "internalising score". The
highest scores with the subscales are found with "withdrawn" and "social
problems". But also "thought problems" and "attention problems" score over 60.
The VCFS children show more behavior problems and personality problems than the
matched control children with a craniofacial anomaly. The differences are highly
statistically significant.
PMID- 10191435
TI - Corticosteroids in head injury--the CRASH trial.
PMID- 10191436
TI - Gastric decontamination--a view for the millennium.
AB - The management of acute poisoning remains an important part of accident and
emergency (A&E) care. Three gastric decontamination procedures have been widely
used: gastric lavage, ipecac, and activated charcoal. Their role has recently
been reviewed and position statements developed by working groups of the American
Academy of Clinical Toxicology and the European Association of Poisons Centres
and Clinical Toxicologists. These have important implications for A&E, as they
indicate that activated charcoal is now the agent of choice for most poisons, but
than in most situations it is probably only effective if given within an hour of
overdose. Ipecac is effectively obsolete and gastric lavage has a narrow range of
indications, principally for potentially serious amounts of agents not adsorbed
by charcoal. Protocols for care of overdose patients should be modified
accordingly.
PMID- 10191437
TI - Injury control strategies: extending the quality and quantity of data relating to
road traffic accidents in children.
AB - This review describes how an extended database of information can provide the
opportunity to go beyond the traditionally distinct health, engineering, and
education initiatives in order to identify the effectiveness of more overarching
policies for injury control. Such information can be used to raise awareness and
to encourage community participation in designing a road traffic accident
prevention strategy.
PMID- 10191438
TI - Carbon monoxide: not gone, not to be forgotten.
PMID- 10191439
TI - Carbon monoxide poisoning: an update.
PMID- 10191440
TI - Carbon monoxide poisoning treated with hyperbaric oxygen: metabolic acidosis as a
predictor of treatment requirements.
AB - A retrospective case note analysis was made of patients who received hyperbaric
oxygen for carbon monoxide poisoning and were admitted to the Royal Naval
Hospital Haslar between 1991 and 1995. Males predominated (38 v 10) as did cases
of deliberate self poisoning (31 v 17). The most common presenting feature was
unconsciousness, which is an indication for hyperbaric oxygen and therefore
reflects referral patterns. If patients had not recovered completely after one
hyperbaric exposure further treatments were given. The initial hydrogen ion
concentration of those requiring more than one treatment was significantly higher
than those who recovered after the first treatment. The initial
carboxyhaemoglobin (COHb) concentration showed only a trend to being higher in
the multiple treatment group. Although metabolic acidosis is well recognised, its
relationship to treatment requirements has not been shown previously. Initial
COHb does not always correlate well with severity of poisoning which relates to
the mechanism of toxicity of carbon monoxide: binding of carbon monoxide to the
intracellular oxygen carrying proteins (for example cytochromes) rather than
solely to haemoglobin. These findings are consistent with this mechanism and
suggests that initial acidosis is a better predictor of treatment requirements
and severity than initial COHb.
PMID- 10191441
TI - British Hyperbaric Association carbon monoxide database, 1993-96.
AB - OBJECTIVES: To study the referral pattern of patients, poisoned with carbon
monoxide and subsequently transferred to British hyperbaric oxygen facilities,
from April 1993 until March 1996 inclusive. METHODS: A standard dataset was used
by hyperbaric facilities within the British Hyperbaric Association. The data on
each patient were sent in confidence to the Hyperbaric Unit at Whipps Cross
Hospital for analysis. The epidemiology of poisoning and the population studied
were analysed. Times of removal from exposure, referral to a hyperbaric facility,
arrival at the hyperbaric facility, and start of treatment were recorded. Data on
the outcome of the episode were documented in one of the contributing facilities.
RESULTS: 575 patients exposed to carbon monoxide were reported as being referred
to British hyperbaric facilities in the three years, the busiest facilities being
in London and Peterborough. The proportions of accidental and non-accidental
exposures were 1:1.05. Of the accidental exposures, central heating faults were
responsible in 71.5% of cases (n = 206). Smoke inhalation from fires was
responsible for a further 13.5% (n = 39). The mean delay to arrival in a
hyperbaric oxygen facility was 9 hours and 15 minutes after removal from
exposure. Recovery after treatment was sometimes incomplete. CONCLUSIONS: The
reported pattern of referral was regionally weighted towards the south east of
England. Smoke inhalation victims were often not referred for hyperbaric oxygen
treatment. The delay to treatment was multifactorial; and the mean delay was well
in excess of six hours. There is room for improvement in the consistency and
speed of referral. Treatment schedules require standardisation. A central advice
and referral service would be helpful.
PMID- 10191442
TI - Systemic hormonal, electrolyte, and substrate changes after non-thermal limb
injury in children.
AB - Relatively little is known regarding the hormonal changes after injury in
children. Adult protocols are often applied to children, although the latter
often have different physiological responses to trauma. Twenty children with an
angulated displaced fracture of the radius and/or ulna (injury severity score 9)
were studied prospectively for changes in adrenaline, noradrenaline, cortisol,
angiotensin II, arginine vasopressin, urea, electrolytes, and glucose. Two blood
samples were taken: one an arrival at the accident and emergency department and
one preoperatively several hours later. There were marked increases in
adrenaline, noradrenaline, cortisol, and arginine vasopressin above the normal
range. Five (25%) cases demonstrated greater early increases in adrenaline than
those reported for adult injuries of similar severity. Early hypokalaemia in four
cases had corrected towards normal within a few hours, without potassium
supplementation.
PMID- 10191443
TI - Older people's use of ambulance services: a population based analysis.
AB - OBJECTIVE: To investigate the use of emergency and non-urgent ambulance transport
services by people aged 65 years and over. SETTING: The study was undertaken in
Queensland where the Queensland Ambulance Services (QAS) is the sole provider of
emergency pre-hospital and non-urgent ambulance services for the entire state.
METHODS: The age and sex of 351,000 emergency and non-urgent cases treated and
transported by the QAS from July 1995 to June 1996 were analysed. RESULTS: People
aged 65 years and over who comprise 12% of the population utilise approximately
one third of the emergency and two thirds of the non-urgent ambulance resources
provided in Queensland. While the absolute number of occasions of service for
females for emergency services is higher than for males, when the data are
stratified for age and sex, males have higher rates of emergency ambulance
service utilisation than females across every age group, and particularly in
older age groups. Gender differences are also found for non-urgent ambulance
usage. The absolute number of occasions of service for older females aged 65 and
over using non-urgent ambulance transport is high, but utilisation patterns on
stratified data reveal similar gender usage patterns across most age groupings,
except at the older age groupings where male usage greatly exceeds female usage.
CONCLUSIONS: As the aged are disproportionately high users of ambulance services,
it will become increasingly important for ambulance services to plan for the
projected increase in the aged population. Emergency pre-hospital care is one of
the few health services along the continuum of care where male usage patterns are
higher than those of females. More information needs to be obtained on the age
and presenting characteristics of those people who are multiple users of the
ambulance service. Such information will assist service planners.
PMID- 10191444
TI - Provision of telephone advice from accident and emergency departments: a national
survey.
AB - This study sought to gain a national picture of the provision of telephone advice
using a postal survey of senior nurses from accident and emergency (A&E) and
minor injury units (MIUs). In all, 268/313 (85%) of hospitals/units responded.
The average number of calls reported as received per day was 15.5 (median 12;
quartiles 6, 20) for weekdays and 21.0 (median 17; quartiles 10, 29) for
weekends. Most (89%) viewed the provision of telephone advice as an important
component of their work, but few units offered staff training for this role or
had implemented protocols or guidelines. Only 5.4% units included the number of
calls received in their department in their workload figures, but 91.9% felt that
they should be. Extrapolation of the data from this study to all 313 A&E and MIUs
in the UK suggests that just under two million calls for telephone advice are
currently made to units each year. Recognition and formalization of this aspect
of work is likely to be of increasing importance given the constraints on
services and the need to manage demand effectively. Future integration of A&E
telephone advice calls with NHS Direct should be considered as a means of
managing demand and avoiding duplication of service provision.
PMID- 10191445
TI - Doctor's assistants--do we need them?
AB - OBJECTIVE: To investigate the potential for the doctor's assistant role within an
accident and emergency (A&E) department in relation to consultant workload.
METHODS: A time and motion evaluation of the activities of four A&E consultants
before and after a doctor's assistant was established as a team member within our
department. A review of the literature was undertaken to allow comparisons with
the American model of the physician assistant within the emergency department.
RESULTS: The initial evaluation indicated that over 20% of the consultant's time
could have been saved if an assistant were available to perform a variety of non
medical tasks. The restudy performed once the assistant was in post indicated
less time was spent by the doctors in "medical" clerical duties (6.7% v 11.5%
time), telephone use (5.6% v 7.7%), and venepuncture/cannula insertion (0.4% v
2.1%), and more time was spent on consultation over cases (15.3% v 11.3%) and
supervision of other staff (9.3% v 4.1%). These five areas changed significantly
(p = 0.005 by paired t test). CONCLUSIONS: The doctor's assistant may have a role
in reprofiling the workload of senior doctors in A&E departments in the UK. They
may also have a role in reducing the pressure on junior doctors, though this
effect was not evaluated.
PMID- 10191446
TI - Tissue donation after death in the accident and emergency department: an
opportunity wasted?
AB - OBJECTIVE: To investigate whether the accident and emergency department (A&E) is
a potential source of tissues for donation, from non-heart beating donors
(NHBDs). METHODS: A telephone survey of 30 A&E departments was conducted to
determine current tissue harvesting practices from NHBDs. The potential number of
tissue donors in our own medium sized district general hospital A&E department
was estimated. Senior nursing staff were asked to complete a questionnaire to
establish their knowledge, attitudes, and experience of tissue harvesting from
NHBDs. RESULTS: Only seven of the 30 A&E departments surveyed (23%) had an active
involvement in requesting tissue donation after a sudden death. Several others
had limited experience. The level of involvement was unrelated to department
size. In our own A&E department, there were 110 deaths in 1995. Tissue donation
had occurred on just three occasions. However, departmental staff attitudes
towards reducing this shortfall were positive. CONCLUSIONS: The A&E department is
a resource of tissues for donation, which is currently under used.
PMID- 10191447
TI - A risk management audit: are we complying with the national guidelines for
sedation by non-anaesthetists?
AB - OBJECTIVES: To assess the effect of a preprinted form in ensuring an improved and
sustained quality of documentation of clinical data in compliance with the
national guidelines for sedation by non-anaesthetists. DESIGN: The process of
retrospective case note audit was used to identify areas of poor performance,
reiterate national guidelines, introduce a post-sedation advice sheet, and
demonstrate improvement. SETTING: Emergency Department, Musgrove Park Hospital,
Taunton. SUBJECTS: Forty seven patients requiring sedation for relocation of a
dislocated shoulder or manipulation of a Colles' fracture between July and
October 1996 and July and October 1997. MAIN OUTCOME MEASURES: Evidence that the
following items had been documented: consent for procedure, risk assessment,
monitored observations, prophylactic use of supplementary oxygen, and discharging
patients with printed advice. Case note review was performed before (n = 23) and
after (n = 24) the introduction of a sedation audit form. Notes were analysed for
the above outcome measures. The monitored observations analysed included: pulse
oximetry, respiratory rate, pulse rate, blood pressure, electrocardiography, and
conscious level. RESULTS: Use of the form significantly improved documentation of
most parameters measured. CONCLUSIONS: Introduction of the form, together with
staff education, resulted in enhanced documentation of data and improved
conformity with national guidelines. A risk management approach to preempting
critical incidents following sedation, can be adopted in this area of emergency
medicine.
PMID- 10191448
TI - Metal detector and swallowed metal foreign bodies in children.
AB - OBJECTIVE: To evaluate a metal detector to diagnose swallowed radio-opaque metal
foreign bodies (MFBs) in children, and whether they can detect non-radio-opaque
MFBs. METHODS: In a prospective study, 231 children, who presented to the
accident and emergency department with a history of swallowing MFBs, were
evaluated by the metal detector as well as radiography to confirm and locate the
presence or absence of MFBs. RESULTS: A definite history of swallowing a MFB by
the child was given by 186 (81%) parents. The metal detector located MFBs in 183
children and radiographs confirmed radio-opaque MFBs in 181. In the remaining 45
(19%), when swallowing was suspected and not definite, both metal detector and
radiography confirmed the presence of a MFB in only four. CONCLUSION: A high
detection rate of swallowed MFBs was observed in this study, using a metal
detector. It is also of value to detect non-radio-opaque MFBs like aluminium. The
detection of MFBs is high when the history of swallowing is definite.
PMID- 10191449
TI - Teaching and learning evidence based medicine skills in accident and emergency
medicine.
PMID- 10191450
TI - Management of vaginal bleeding presenting to the accident and emergency
department.
PMID- 10191451
TI - Towards evidence based emergency medicine: best BETs from the Manchester Royal
Infirmary. Eye patches and corneal abrasion.
PMID- 10191452
TI - Towards evidence based emergency medicine: best BETs from the Manchester Royal
Infirmary. Paracetamol or ibuprofen in febrile children.
PMID- 10191453
TI - Towards evidence based emergency medicine: best BETs from the Manchester Royal
Infirmary. Alkalinisation in the management of tricyclic antidepressant overdose.
PMID- 10191454
TI - Towards evidence based emergency medicine: best BETs from the Manchester Royal
Infirmary. Collar and cuff or sling after fracture of the clavicle.
PMID- 10191455
TI - Towards evidence based emergency medicine: best BETs from the Manchester Royal
Infirmary. Curettage or silver nitrate for pyogenic granulomas on the hand.
PMID- 10191456
TI - Towards evidence based emergency medicine: best BETs from the Manchester Royal
Infirmary. Support for uncomplicated shaft of humerus fractures.
PMID- 10191457
TI - Managing a bed crisis.
PMID- 10191459
TI - Management of laryngeal foreign bodies in children.
AB - Foreign body aspiration is one of the leading causes of accidental death in
children. Food items are the most common items aspirated in infants and toddlers,
whereas older children are more likely to aspirate non-food items. Laryngeal
impaction of a foreign body is very rare as most aspirated foreign bodies pass
through the laryngeal inlet and get lodged lower down in the airway. Two rare
cases of foreign body aspiration with subglottic impaction in very young children
(under 2 years of age) are described. In both the cases subglottic impaction
occurred consequent to attempted removal of foreign body by blind finger
sweeping. The clinical presentation, investigations, and management of these rare
cases are discussed.
PMID- 10191458
TI - Chickenpox pneumonia: case report and literature review.
AB - The incidence of primary chickenpox infection in young adults appears to be
rising in the UK and other developed countries. The infection is more severe in
adults than in children and complications, including pneumonia, are more
frequent. An illustrative case of severe chickenpox pneumonia in an
immunocompetent, non-pregnant adult smoker is presented. The epidemiology and
pathology of the disease is discussed and a review of current management in the
emergency department and the intensive care unit is presented. Strategies for the
prevention of chickenpox pneumonia are also discussed.
PMID- 10191461
TI - Glioblastoma presenting as carbon monoxide poisoning.
PMID- 10191460
TI - An acutely painful elbow as a first presentation of von Willebrand's disease.
AB - A 26 year old woman presented to the accident and emergency department with a
painful right elbow. There had been no history of trauma. Clinical examination
suggested an effusion, which was confirmed on radiological examination. Her elbow
was aspirated and revealed a haemarthrosis. Subsequent investigations revealed a
diagnosis of von Willebrand's disease (vWD). A spontaneously occurring effusion
of the elbow may be due to a haemarthrosis. Aspiration of blood in the absence of
trauma may lead to a diagnosis of an occult coagulopathy in addition to relieving
pain. The diagnosis and treatment of vWD is discussed.
PMID- 10191462
TI - Covert tamponade.
PMID- 10191463
TI - Acute airway obstruction--an unusual cause.
PMID- 10191464
TI - Non-invasive cardiac output assessment in children.
PMID- 10191465
TI - Safe use of thrombolysis in acute myocardial infarction.
PMID- 10191466
TI - Capnography and "major" accident and emergency departments in East Anglia.
PMID- 10191467
TI - Violence in the accident and emergency department: liaison with the police.
PMID- 10191468
TI - Atosiban, an oxytocin receptor blocking agent: pharmacokinetics and inhibition of
milk ejection in dairy cows.
AB - Plasma concentrations of the oxytocin receptor blocking agent Atosiban were
measured at 2, 4, 10, 15 and 20 min after injection of 5, 10, 20 and 50
micrograms Atosiban/kg body weight in six dairy cows. The half life of Atosiban
was 18 min and the total body clearance was 3301 ml/min. Intramammary pressure
(IMP) within the teat cistern was measured in six cows before and after i.v.
injection of 0 or 20 micrograms Atosiban/kg body weight and repeated injections
of 0.2 or 0.5 i.u. oxytocin. IMP was also measured in eleven cows after injection
of 0, 10 or 50 micrograms Atosiban/kg body weight: in seven during oxytocin
infusions, in four after oxytocin injections in successively increasing dosages
(0.05, 0.1, 0.2, 0.5, 1 and 10 i.u.). The occurrence of milk ejection was
indicated by a rise in IMP. After injection of 20 micrograms Atosiban/kg body
weight, 0.2 i.u. oxytocin did not induce an IMP rise before 48 min, whereas 0.5
i.u. oxytocin induced an IMP rise within 4 min. The time from the start of
infusion until the beginning of the IMP rise and the duration of IMP rise during
oxytocin infusions both increased, whereas the IMP rise itself was diminished by
increasing Atosiban dosages. The amount of injected oxytocin necessary to induce
an IMP response increased with increasing Atosiban dosages. Atosiban was shown to
have a powerful effect in inhibiting milk ejection in dairy cows.
PMID- 10191469
TI - Heat-treated whole cottonseed: effect of dietary protein concentration on the
performance and amino acid utilization by the mammary gland of dairy cows.
AB - The effects of replacing whole cottonseed by heated whole cottonseed at two
levels of crude protein on amino acid (AA) utilization by the bovine mammary
gland were investigated. Four Israeli Holstein cows were used in a 4 x 4 Latin
square design with 2 x 2 factorial arrangements. Diets were formulated to contain
two levels of crude protein (CP), normal (160 g CP/kg dry matter) and low (140 g
CP/kg dry matter), and two levels of rumen undegradable protein (UDP), high (380
g UDP/kg CP) and low (350 g UDP/kg CP). Whole cottonseed was quantitatively
substituted by heated whole cottonseed to formulate the high UDP diets. Intakes
of dry matter and organic matter were similar for all treatments and averaged
15.9 and 14.4 kg/d respectively. Yields of milk and its constituents were similar
for all treatments. Milk yield averaged 23.1 kg/d and this contained (per kg)
32.3 g CP, 25.4 g total casein and 47.5 g lactose. The milk fat content was lower
in the cows given the high UDP diets, averaging 34.6 g/kg compared with 38.9 g/kg
in the cows fed on the diets with low UDP. Plasma AA concentrations were similar
for all treatments apart from Leu and Ile, which were higher in the cows given
the high CP diets: 152 and 103 microM compared with 183.8 and 131.5 microM for
the low CP diets. Net extraction and balance of essential AA across the half
udder suggested that essential AA were supplied in amounts sufficient to meet
milk protein requirements for all treatments. The surplus AA supplied as a result
of feeding the high dietary CP were probably catabolized via an enhanced
oxidative pathway, possibly in the liver, presumably as a passive response to
their disposal.
PMID- 10191470
TI - Effect of endocrine and paracrine factors on protein synthesis and cell
proliferation in bovine hoof tissue culture.
AB - Laminitis is a major cause of lameness in dairy cattle, and is widely attributed
to a defect in the horny tissue that gives the hoof its mechanical strength.
Defective horn is associated with, and may be preceded by, impaired keratin
deposition in the hoof epidermis. The cause of abnormal keratin deposition is not
easily identified but, like epidermal keratinization in other tissues, is likely
to be controlled by hormones and the paracrine action of locally produced growth
factors. The hormonal regulation of keratin synthesis and cell proliferation in
the bovine hoof was studied using tissue explants in organ culture. As the
highest incidence of laminitis is in early lactation, the study focused on
insulin, cortisol and prolactin, three hormones implicated in lactogenesis and
galactopoiesis. Incubation of tissue explants for 24 h in medium containing
insulin (10-5000 ng/ml) stimulated protein synthesis measured by incorporation of
35S-labelled amino acids. Histochemical examination showed that insulin binding
co-localized with the site of protein synthesis. Insulin also stimulated DNA
synthesis, an index of cell proliferation, which was measured by incorporation of
[3H]methyl thymidine. Cortisol (10-5000 ng/ml) decreased protein synthesis,
whereas prolactin (10-5000 ng/ml) had no significant effect on protein or DNA
synthesis. Epidermal growth factor (10-200 ng/ml), a potent inhibitor of
keratinization in other tissues, stimulated protein synthesis compared with
untreated controls. Epidermal growth factor binding was located microscopically
to the germinal and differentiating epidermal layers. SDS-PAGE and fluorography
showed that the population of proteins synthesized in the presence of any hormone
or growth factor combination did not differ from that in untreated controls and
included the keratins involved in horn deposition. The results show that bovine
hoof keratinization is under endocrine and growth factor control, and suggest
that systemic changes in lactogenic hormones may act to inhibit keratin
deposition.
PMID- 10191471
TI - Spatial and temporal expression of insulin-like growth factor-I, insulin-like
growth factor-II and the insulin-like growth factor-I receptor in the sheep fetal
mammary gland.
AB - The mammary gland is an example of a tissue of epidermal origin that depends for
the development of its characteristic morphology on underlying mesenchymal cells.
The interaction between mesenchyme and epithelium appears to be mediated by
polypeptide growth factors. In situ hybridization has been used to study, in the
mammary gland of female sheep fetuses, the distribution of mRNA for the mammary
mitogens, insulin-like growth factor (IGF)-I and IGF-II, and the IGF-I receptor,
from 10 to 20 weeks of intrauterine life (term is approximately 22 weeks). At 10
weeks, secondary ducts had formed from the primary duct. By week 20, the gland
had increased in volume and complexity, showing primitive lobules embedded in
intralobular connective tissue disposed around main ducts. IGF-I and IGF-II mRNA
were expressed in cells of the intralobular connective tissue underlying the
epithelium, while the IGF-I receptor was expressed in epithelium. Quantitation by
absorbance measurements showed that mRNA expression increased with pregnancy
stage for IGF-I and IGF-II, but not significantly for the IGF-I receptor, and
that IGF-II was more highly expressed than IGF-I. A role for the IGF system in
mediating mesenchymal epithelial interactions in mammary development is
indicated.
PMID- 10191473
TI - Structural features of a peptide corresponding to human kappa-casein residues 84
101 by 1H-nuclear magnetic resonance spectroscopy.
AB - The peptide Val-Arg-Arg-Pro-Asn-Leu-His-Pro-Ser-Phe-Ile-Ala-Ile-Pro-Pro- Lys-Lys
Ile, which corresponds to residues 84-101 of human kappa-casein, has been
synthesized and its conformation preferences determined by 1H-nuclear magnetic
resonance spectroscopy in dimethyl sulphoxide. The peptide adopted a largely
extended chain conformation in solution and there was evidence for the presence
of a beta-turn involving residues Pro87-His90 of human kappa-casein. The presence
of a turn in this position would make the physiologically significant Arg85
residue of human kappa-casein (which is equivalent to Arg97 in bovine kappa
casein) unavailable for interaction with Asp249 of bovine chymosin, and may
partly explain why human kappa-casein is hydrolysed more slowly than its bovine
counterpart by bovine chymosin.
PMID- 10191472
TI - Insulin secretion and intestinal peptides during lactation in sheep.
AB - Intravenous infusions of glucose and/or glucagon-like peptide-1(7-36)-amide (GLP)
or somatostatin-28 (S28) were administered to dry and lactating sheep and changes
in plasma glucose and serum insulin were followed before, during and after
infusion. Basal serum insulin concentrations were significantly lower in
lactating sheep but there was no significant difference in plasma glucose
concentrations. During glucose infusion, changes in serum insulin concentrations
were diminished by comparison with those in dry animals. GLP stimulated insulin
secretion during hyperglycaemia in both dry and lactating sheep but,
proportionately, the response was significantly greater in the lactating animals.
S28 inhibited glucose-stimulated insulin secretion in both dry and lactating
sheep and there was no significant difference in the extent of the inhibition
between the two physiological states. S28 infusion also inhibited the secretion
of GLP from the intestinal tract and this effect was significantly greater in the
lactating animals. The results demonstrate a difference in response in the
lactating animal to GLP compared with S28. A possible explanation of the
difference is a decreased sensitivity (i.e. increased Km) of the pancreas to the
insulinotropic effects of GLP but an increased sensitivity to the inhibitory
effects of S28 at tissues other than the pancreas in lactation.
PMID- 10191474
TI - Effects of high pressure and heat treatment on the mineral balance of goats'
milk.
AB - Changes in the distribution of minerals in skim goats' milk by high pressure (400
MPa) and/or heat (85 degrees C for 30 min) treatment have been studied. Heat
treatment caused reduced solubility of the calcium, magnesium and phosphorus, and
this increased with the severity of heating. In contrast, high pressure released
different levels of micellar elements into the soluble phase without causing
appreciable changes in pH or ionic calcium concentration. The levels of soluble
salts returned to their original values when the heated samples were subjected to
high pressure. However, heating pressurized milk resulted in concentrations of
soluble minerals that were lower than in control milks, and close to values found
in heated milks. The salt balance in goats' milk was less affected by high
pressure treatment at 75 degrees C than was that of cows' milk. These results are
discussed in relation to the effects of high pressure and heat treatment on
mineral equilibrium and micellar structure.
PMID- 10191475
TI - Contribution of the lactoperoxidase system to the keeping quality of pasteurized
milk.
AB - The lactoperoxidase system is a naturally occurring antimicrobial system found in
milk, with lactoperoxidase, thiocyanate and hydrogen peroxide as its components.
The keeping quality of milk pasteurized at 72 degrees C for 15 s was found to be
better than that of milk heated at 80 degrees C for 15 s. This agrees with
previous findings and is usually attributed to heat shocking of spores. However,
complete deactivation of lactoperoxidase occurred at 80 degrees C-15 s, whereas
at 72 degrees C-15 s residual lactoperoxidase activity was approximately 70%,
which may provide an alternative explanation. Higher levels of hypothiocyanite
(the major antimicrobial agent produced by the lactoperoxidase system) were also
detected in milk processed at 72 than at 80 degrees C, which supports the theory
that the lactoperoxidase system has a role in the keeping quality of pasteurized
milk. Of all the methods evaluated, titratable acidity and alcohol stability gave
the most consistent estimates of keeping quality, while dissolved oxygen was a
good indication of the onset of spoilage. Lactoperoxidase activity decreased with
temperature more rapidly between 70 and 80 degrees C than is usual for an enzyme
over a 10 deg C range.
PMID- 10191476
TI - Preparation and characterization of the N and C monoferric lobes of buffalo
lactoferrin produced by proteolysis using proteinase K.
AB - The two glycosylated N- and C-terminal lobes of buffalo lactoferrin have been
produced by limited proteolysis using proteinase K. Lactoferrin is a single chain
glycoprotein of molecular mass 80 kDa with two iron-binding sites and two
structural lobes connected by a short peptide. Purified samples of lactoferrin,
isolated from buffalo colostrum, were subjected to hydrolysis using trypsin,
chymotrypsin, pepsin, subtilisin and proteinase K. The first three proteinases
produced two major fragments of approximately 35 and 23 kDa together with small
molecular mass peptides. Trypsin and chymotrypsin partly digested lactoferrin,
while pepsin converted all the intact lactoferrin into fragments. Subtilisin
hydrolysis produced fragments of 40 and 26 kDa together with low molecular mass
peptides. However, SDS-PAGE of the proteinase K hydrolysis product gave a clear
band at 40 kDa together with a band indicating a substantial quantity of low
molecular mass peptides (< 14.4 kDa). Upon ion-exchange chromatography this
product gave two major fractions, which were further purified by gel filtration
and identified as the C and N lobes from their N-terminal sequences. Thus, the 40
kDa band in SDS-PAGE of the proteinase K hydrolysis product contained two
fragments of equal molecular mass. On further hydrolysis with proteinase K, the N
lobe was completely hydrolysed into low molecular mass peptides, while only a
small fraction of the C lobe was converted into small products. This suggested
that an inhibitory fragment was present in the C lobe that was released on
hydrolysis to small fragments and prevented complete digestion of the C lobe by
high-affinity binding to the active site of proteinase K. This fragment was
isolated from the lactoferrin-proteinase K complex and its sequence determined to
be Val-Ala-Gln-Gly-Gly-Ala-Ala-Gly-Leu-Ala. Circular dichroism studies indicated
a high alpha-helical content in the native lactoferrin while comparatively lower
helical structures were present in the N and C lobes. In addition, the iron
saturations of the N and C lobes appeared to be lower than that of the native
protein.
PMID- 10191477
TI - Influence of milking interval on the total bacterial count in a simulated
automatic milking system.
PMID- 10191478
TI - Effect of heat treatment on anti-rotavirus activity of bovine colostrum.
PMID- 10191479
TI - Production of calcium-reduced milks using an ion-exchange resin.
PMID- 10191480
TI - Component PP3 from bovine milk is a substrate for transglutaminase. Sequence
location of putative crosslinking sites.
PMID- 10191481
TI - [Isotopic study with double phase 99mTc-sestamibi in the localization of
parathyroid gland lesions].
AB - BACKGROUND: The use of preoperative imaging in patients with hyperparathyroidism
remains controversial. The aim of this study is to assess the usefulness of the
double-phase 99mTc-sestamibi scintigraphy in the diagnosis of abnormal
parathyroid glands in patients with primary hyperparathyroidism. PATIENTS AND
METHODS: We studied 60 patients presenting with primary hyperparathyroidism who
were referred to surgery; four of them had been unsuccessfully operated. 99mTc
sestamibi scintigraphy were performed in all patients previously to surgery.
Scintigraphic technique: planar imaging of the neck and thorax was done in the
anterior view at 15 and 150 min postinjection of 740 MBq (20 mCi) of 99mTc
sestamibi. RESULTS: Surgery found 57 adenomas (2.59 [SD, 5.84] g; range 0.160
40), 6 hyperplastic glands (0.34 [SD, 0.26] g) and one carcinoma 8.2 g. The 99mTc
sestamibi was able to localize correctly 60 out of 64 lesions (55/57 adenomas,
4/6 hyperplastic glands and 1/1 carcinoma) (global sensitivity of 94%, adenomas
sensitivity of 96%, positive predictive value of 97% and specificity of 98%).
Isotopic imaging detected the abnormal tissue in all patients who had undergone
unsuccessful previous surgery. PTH (4 [SD, 1.51] pmol/l) and calcium
postoperative serum levels (2.13 [SD, 0.22] mmol/l) showed curation of all
patients. CONCLUSION: Double phase parathyroid scintigraphy with 99mTc-sestamibi
is the method of choice to localize abnormal parathyroid glands.
PMID- 10191482
TI - [The Mediterranean diet improves the profile of male smokers compared with the
diet recommended by the American Cholesterol Program (NCEP-I)].
AB - BACKGROUND: A study of the effect of smokers' diets on their atherogenic lipidic
profile. SUBJECTS AND METHODS: 41 healthy males (32 non-smokers and 9 smokers)
consumed consecutively a diet low in fat and rich in carbohydrates (28% total fat
content < 10% saturated fats, and 57% carbohydrates), and a diet rich in
monounsaturated fatty acids (38% total fat content with 22% monounsaturated
fats). At the end of each dietary period, adhesion was confirmed by
quantification of LDL cholesterol esters, plasma lipids and insulin levels.
RESULTS: There were no significant differences between the age or the body mass
of the groups of smokers or non-smokers. After both diets tobacco was found to
have a significant effect on triglyceride levels (p < 0.0007), HDLc (p < 0.007),
apo A-I (p < 0.02) and the LDLc/HDLc ratio (p < 0.005), revealing an interaction
between diet and both HDLc levels (p < 0.004) and LDLc/HDLc ratios (p < 0.003).
With the low fat and high monounsaturated fatty acid content diets smokers
presented higher triglyceride levels (both with p < 0.0002) and LDLc/HDLc ratios
(p < 0.0002 and p < 0.05, respectively) and lower levels of apo A-I (p < 0.002
and p < 0.004, respectively). However, in smokers the HDLc levels were only
reduced after the low fat diet (p < 0.0003) and after the diet with a high
monounsaturated fat content there was a rise in HDLc levels (p < 0.02) and a drop
in the LDLc/HDLc ratio (p < 0.005) compared to the group of non-smokers. There
were no significant differences in the insulin levels between groups. CONCLUSION:
The atherogenic lipidic profile of smokers is due to an effect of tobacco on the
lipidic metabolism. This atherogenic profile is accentuated with a low fat diet
rich in carbohydrates and can be rectified to some degree with a diet with a high
monounsaturated fatty acid content.
PMID- 10191483
TI - [Epidemiology of yeast colonization and oropharyngeal infection other than
Candida albicans in patients with HIV infection].
AB - BACKGROUND: An increasing frequency of opportunistic fungal infections in
immunosuppressed patients in recent years. Concurrent with this finding, it has
been noted an increasing use of fluconazole. In addition, non-Candida albicans
species (NCAS), most of which are fluconazole-resistant have been increasing
isolated. The aim of this study was to investigate the epidemiology of
colonization and infection due to NCAS in HIV-infected patients. PATIENTS AND
METHODS: A cross sectional study was conducted with HIV-infected patients in
different stages, who were attended at two hospitals in Alicante, Spain. We
assessed the prevalence and microbiology of oropharyngeal colonization and
infection due to Candida spp., and its fluconazole susceptibility patterns. To
determine the clinical risk factors for the development of fluconazole
resistance, we carried out a case-control study with prevalent cases. RESULTS: We
studied 168 strains from 153 patients. NCAS were isolated in 32 (21%) of them, 25
(77%) were colonized, and 5 (26%) had infection due to NCAS. The most common
isolate was Candida glabrata (n = 15). MICs were significantly higher for NCAS
than for Candida albicans species, with a MIC50 of 16 and 0.25 microgram/ml,
respectively, and a MIC90 of 128 micrograms/ml and 8 micrograms/ml (p = 0.0001).
The median CD4 cell count in patients with NCAS was 0.06 x 10(9)/l, and 0.19 x
10(9)/l patients with Candida albicans (p = 0.009). Overall, 56% of the patients
with NCAS and 41% of the patients with Candida albicans had been treated with
fluconazole (p = 0.1). CONCLUSIONS: NCAS are isolated in a high proportion of HIV
infected patients. Most of the NCAS have a decreased susceptibility to
fluconazole. The only risk factor associated with the acquisition of NCAS in HIV
infected patients is an advanced immunosuppression.
PMID- 10191484
TI - [Demographic characterization, consultation reasons and prevalent morbidity in
the African immigrating community of the Maresme district].
AB - BACKGROUND: To know the demographic condition, main symptoms and diagnosis in
adult African immigrants from a reference Hospital. PATIENTS AND METHOD: A
prospective protocol between 1984-1994. RESULTS: 1,321 immigrants were
considered. Most of them had an unstable job and illegal situation and they did
not speak any European language. Abdominal pain was the most common symptom. The
most frequent diagnoses were parasitic/infections and digestive and
haematological diseases. CONCLUSIONS: Immigration is not a risk for public
health. The illegal situation carries poor sanitary conditions. The clinical
protocols help to overcome cultural and idiomatic barriers.
PMID- 10191485
TI - [Evaluation activities a symptom of good health].
PMID- 10191486
TI - [Insulin resistance: new prospects].
PMID- 10191487
TI - [Primary gastrointestinal lymphoma in patients infected with HIV: study of 15
cases in a series of 76 patients with non-Hodgkin's lymphoma and HIV infection].
AB - BACKGROUND: To analyze the main clinical and biological data and the response to
therapy in 15 patients with primary gastrointestinal lymphoma (PGIL) from a
series of 76 patients with HIV related non-Hodgkin's lymphoma (NHL) diagnosed in
a single institution in a 13 years period. PATIENTS AND METHODS: The main
clinical, biological and evolutive data were recorded. Pathologic diagnosis of
PGIL was made according to the REAL classification. Clinical stage was determined
by the Ann Arbor system modified by Rohatiner et al. Response to therapy as well
as overall survival (OS) were studied. Results were compared with non-PGIL HIV
related NHL patients. RESULTS: Mean age of the series was 38 years. Thirteen
patients were male, and 8 intravenous drug abusers. Then had bad performance
status (ECOG 2-4) and 11 B symptoms. All patients had a high grade malignant PGIL
and the localization was gastric in 10 cases. The most frequent symptoms were
abdominal pain (11 cases), gastrointestinal bleeding (4) and dysphagia (3). Ten
patients had advanced stages (IIE2-IV). The median CD4 cell count was lower in
PGIL patients (92 x 10(6)/l vs 148 x 10(6)/l; p < 0.05). Thirteen patients
received intensive chemotherapy with CHOP regimen (in 5 surgical procedures were
previously made). Complete response (CR) was obtained in 4 patients (31%) and 1
of them relapsed. Median OS was 10 months vs 16 months non-PGIL HIV-related
lymphoma patients (p < 0.05). CONCLUSIONS: PGIL in HIV patients often presented
advanced stages and high grade of malignancy. The most common localization is the
stomach, and these patients usually have bad performance status and a low CD4
lymphocyte count. Response to therapy is poor. In our series OS was worse in PGIL
patients than in the rest of HIV-related NHL, possibly due to the high degree of
immunosuppression in the formers.
PMID- 10191489
TI - [Safety of antithyroid drugs in pregnancy].
PMID- 10191488
TI - [Biomedical research in Spain (II). Assessment of the Health Research Fund (FIS)
through the research projects funded in 1988-1995 for research centers, colleges,
and schools].
PMID- 10191490
TI - [Prevalence of HTLV-I/II infection in various population groups in Gran Canaria].
PMID- 10191491
TI - [Use of opiate analgesics in Spain. The rol of codeine].
PMID- 10191492
TI - [Aseptic thrombosis of the intracranial venous sinuses in a patient with kidney
transplantation and toxic levels of cyclosporine].
PMID- 10191493
TI - [Vasculitis and hepatitis C virus].
PMID- 10191494
TI - Classification and evolution of EF-hand proteins.
AB - Forty-five distinct subfamilies of EF-hand proteins have been identified. They
contain from two to eight EF-hands that are recognizable by amino acid sequence
as being statistically similar to other EF-hand domains. All proteins within one
subfamily are congruent to one another, i.e. the dendrogram computed from one of
the EF-hand domains is similar, within statistical error, to the dendrogram
computed from another(s) domain. Thirteen subfamilies--including Calmodulin,
Troponin C, Essential light chain, Regulatory light chain--referred to
collectively as CTER, are congruent with one another. They appear to have evolved
from a single ur-domain by two cycles of gene duplication and fusion. The
subfamilies of CTER subsequently evolved by gene duplications and speciations.
The remaining 32 subfamilies do not show such general patterns of congruence;
however, some--such as S100, intestinal calcium binding protein (calbindin 9 kd),
and trichohylin--do not form congruent clusters of subfamilies. Nearly all of the
domains 1, 3, 5, and 7 are most similar to other ODD domains. Correspondingly the
EVEN numbered domains of all 45 subfamilies most closely resemble EVEN domains of
other subfamilies. Many sequence and chemical characteristics do not show
systemic trends by subfamily or species of host organisms; such homoplasy is
widespread. Eighteen of the subfamilies are heterochimeric; in addition to
multiple EF-hands they contain domains of other evolutionary origins.
PMID- 10191495
TI - Structures of EF-hand Ca(2+)-binding proteins: diversity in the organization,
packing and response to Ca2+ binding.
AB - The growing database of three-dimensional structures of EF-hand calcium-binding
proteins is revealing a previously unrecognized variability in the conformations
and organizations of EF-hand binding motifs. The structures of twelve different
EF-hand proteins for which coordinates are publicly available are discussed and
related to their respective biological and biophysical properties. The classical
picture of calcium sensors and calcium signal modulators is presented, along with
variants on the basic theme and new structural paradigms.
PMID- 10191496
TI - The Ca2+ pumps and the Na+/Ca2+ exchangers.
AB - The Ca2+ ATPases or Ca2+ pumps transport Ca2+ ions out of the cytosol, by using
the energy stored in ATP. The Na+/Ca2+ exchanger uses the chemical energy of the
Na+ gradient (the Na+ concentration is much higher outside than inside the cell)
to remove Ca2+ from the cytosol, Ca2+ pumps are found in the plasma membrane and
in the endoplasmic reticulum of the cells. The pumps are probably present in the
membrane of other organelles, but little experimental information is available on
this matter. The Na+/Ca2+ exchangers are located on the plasma membrane. A
Na+/Ca2+ exchanger was found in the mitochondria, but very little is known on its
structure and sequence. These transporters control the Ca2+ concentration in the
cytosol and are vital to prevent Ca2+ overload of the cells. Their activity is
controlled by different mechanisms, that are still under investigation. A number
of the possible isoforms for both types of proteins has been detected.
PMID- 10191497
TI - Ca2+/calmodulin-dependent protein kinase IV and calcium signaling.
AB - Ca2+/calmodulin dependent protein kinase IV (CaMKIV) is a multifunctional, serine
threonine protein kinase that is activated in the presence of increased
intracellular calcium (Ca2+). CaMKIV is a potent mediator of Ca2+ induced gene
expression, primarily through its ability to phosphorylate and activate
transcription factors such as CREB. CaMKIV-dependent activation of CREB is a key
event in the expression of genes involved in the processes of T-cell activation
and neuronal long term potentiation. The focus of this review is to describe the
biochemical regulation of CaMKIV and examine how CaMKIV activates transcription
in response to calcium in both cell and animal models.
PMID- 10191498
TI - Nuclear calcium: a key regulator of gene expression.
AB - Through the evolution of multicellular organisms, calcium has emerged as the
preferred ion for intracellular signalling. It now occupies a pivotal role in
many cell types and nowhere is it more important than in neurons, where it
mediates both the relaying and long-term storage of information. The latter is a
process that enables learning and memory to be formed and requires the activation
of gene expression by calcium signals. Evidence from a number of diverse
organisms shows that transcription mediated by the transcription factor CREB is
critical for learning and memory. Here we review the features of CREB activation
by calcium signals in mammalian cells. In contrast to other transcription
factors, its regulation is dependent on an elevation of nuclear calcium
concentration, potentially placing this spatially distinct pool of calcium as an
important mediator of information storage.
PMID- 10191499
TI - Calcium-binding proteins and development.
AB - The known roles for calcium-binding proteins in developmental signaling pathways
are reviewed. Current information on the calcium-binding characteristics of three
classes of cell-surface developmental signaling proteins (EGF-domain proteins,
cadherins and integrins) is presented together with an overview of the
intracellular pathways downstream of these surface receptors. The developmental
roles delineated to date for the universal intracellular calcium sensor,
calmodulin, and its targets, and for calcium-binding regulators of the
cytoskeleton are also reviewed.
PMID- 10191500
TI - The role of calcium in apoptosis.
AB - In this chapter various aspects of apoptosis or programmed cell death (PCD)
influenced by calcium as a mediator of signal transduction have been reviewed.
Attention has been focused on recently described calcium-binding proteins such as
ALG-2 or on a new calcium/calmodulin-dependent kinase, the death associated
protein kinase or DAP-kinase. Both play a central role in apoptotic processes.
Calcineurin, which normally is involved in the regulation of T-cell
proliferation, is reported to interact with the apoptosis protection protein bcl
2. Its possible involvement in the decision process whether T-cell activation
leads to proliferation or apoptosis is discussed.
PMID- 10191501
TI - New perspectives on S100 proteins: a multi-functional Ca(2+)-, Zn(2+)- and Cu(2+)
binding protein family.
AB - S100 proteins (16 members) show a very divergent pattern of cell- and tissue
specific expression, of subcellular localizations and relocations, of post
translational modifications, and of affinities for Ca2+, Zn2+, and Cu2+,
consistent with their pleiotropic intra- and extracellular functions. Up to 40
target proteins are reported to interact with S100 proteins and for S100A1 alone
15 target proteins are presently known. Therefore it is not surprising that many
functional roles have been proposed and that several human disorders such as
cancer, neurodegenerative diseases, cardiomyopathies, inflammations, diabetes,
and allergies are associated with an altered expression of S100 proteins. It is
not unlikely that their biological activity in some cases is regulated by Zn2+
and Cu2+, rather than by Ca2+. Despite the numerous putative functions of S100
proteins, their three-dimensional structures of, e.g., S100B, S100A6, and S100A7
are surprisingly similar. They contain a compact dimerization domain whose
conformation is rather insensitive to Ca2+ binding and two lateral alpha-helices
III and III, which project outward of each subunit when Ca2+ is bound. Target
docking depends on the two hydrophobic patches in front of the paired EF-hand
generated by the binding of Ca2+. The selectivity in target binding is assured by
the central linker between the two EF-hands and the C-terminal tail. It appears
that the S100-binding domain in some target proteins contains a basic amphiphilic
alpha-helix and that the mode of interaction and activation bears structural
similarity to that of calmodulin.
PMID- 10191502
TI - Annexins.
AB - The annexins are a family of proteins that bind anionic phospholipid surfaces in
a Ca(2+)-dependent manner (general reviews include Raynal & Pollard 1994, Swairjo
& Seaton 1994, Seaton 1996, Mollenhauer, 1997). Due to this functional property,
individual annexins have been discovered independently by numerous laboratories
with diverse experimental goals. Ca2+ characteristically causes the annexins to
shift from a soluble to membrane associated state. This shift is believed to be
the mechanism that underlies annexin cellular function.
PMID- 10191503
TI - Protective effects of selenium, vitamin C and vitamin E against oxidative stress
of cigarette smoke in rats.
AB - Cataractous lenses have been found to have an altered distribution of the
intracellular ionic environment: the concentrations of potassium and magnesium
being decreased and the concentrations of sodium and calcium increased. These
changes arise as a result of changes to lens membrane characteristics causing an
increase in lens membrane permeability. In this study flame atomic absorption
spectroscopy (AAS) was used for calcium, magnesium, iron and zinc determination,
and flame atomic emission spectroscopy (AES) was used for sodium and potassium
contents in normal and cigarette smoke-exposed rat lenses. The methods are
sensitive enough to detect quantitatively all six cations in a single rat lenses.
In this work, six elements, including Ca2+, K+, Na+, Zn2+, Fe2+ and Mg2+ in
experimental rat eye lenses and normal transparent lenses were determined. It was
found that the concentrations of Ca2+, Na+, Zn2+, and Fe2+ were increased
dramatically while K+ and Mg2+ decreased in smoke-exposed rat lenses when
compared to the control rat lenses. There were no significant changes between
'smoked' rats supplied with vitamin C and control groups. A positive correlation
was found also in the other two groups of 'cigarette smoked' animals supplemented
with selenium plus vitamin E and selenium when compared with 'cigarette smoked'
without any supplements. These data provide support for the hypothesis that
cigarette smoking increases the risk of cataract formation. We investigated
whether vitamin C is the most important antioxidant in the body. The roles of
diet with optimum amounts of antioxidant vitamins C and vitamin E and the
antioxidant mineral selenium are discussed.
PMID- 10191504
TI - Superoxide dismutase, catalase and glutathione peroxidase activities in the
lymphoid organs and skeletal muscles of rats treated with dexamethasone.
AB - The effect of dexamethasone (a synthetic glucocorticoid) on the activity of
antioxidant enzymes (superoxide dismutase (SOD), catalase and glutathione
peroxidase) of the lymphoid organs (mesenteric lymph nodes (MLN), spleen and
thymus) was investigated. For comparison with non-immune tissues, skeletal
muscles (soleus and gastrocnemius (GC) were also studied. As an indication of the
occurrence of lipid peroxidation, the content of thiobarbituric acid reactant
substances (TBARs) was also determined. Dexamethasone treatment decreased the
TBARs content of the lymphoid organs and raised it in the GC and soleus muscles.
The activity of Cu/Zn-SOD was reduced in all tissues. However, the activity of Mn
SOD was decreased in the MLN and soleus muscle only. The activity of catalase was
reduced in the MLN and thymus and raised in the spleen and GC and soleus muscles.
The imposed treatment raised the activity of GPX in the MLN, thymus and spleen
and reduced it in GC and soleus muscles. These data led us to postulate that the
mechanism for the therapeutic effect of glucocorticoids as antiinflammatory and
immunosuppressive agents might include modification of antioxidant enzyme
activities.
PMID- 10191505
TI - Impact of various glycosaminoglycans upon cAMP-dependent protein kinase.
AB - The physiological effects of the second messenger cAMP are displayed by cAMP
dependent protein kinase-medicated phosphorylation of specific target proteins
which in turn control diverse cellular functions. We have determined this enzyme
substrate phosphorylation in the presence of various glycosaminoglycans using a
cAMP-dependent protein kinase isolated from rat liver. The results indicate that
sulfated and unsulfated polysaccharides are able to inhibit phosphorylation of
histone type IIa catalysed by cAMP-dependent protein kinase. Based on their
impact upon substrate phosphorylation, glycosaminoglycans can be divided into
three groups: group I with the highest inhibitory effect: dermatan sulfate and
heparan sulfate; group II: chondroitin 4-sulfate and group III with the lowest
inhibitory effect: chondroitin 6-sulfate, keratan sulfate and hyaluronic acid.
PMID- 10191506
TI - Colonization by diatoms and antirheumatic activity of thermal mud.
AB - We have identified diatoms among other thermophilic microorganisms as the main
agents for the colonization of thermal mud resulting in a 'maturation' which
renders the mud suitable to be used for mud-pack treatment of osteoarthrosis
patients. The main effects of the diatom growth are the progressive enrichment of
mud extracts in chlorophyll a parallel to the building up of a sulfoglycolipid
endowed with an anti-inflammatory action. The sulfoglycolipid was also produced
by diatoms isolated from the mud and cultivated in vitro.
PMID- 10191507
TI - Effect of Aspergillus terreus mycotoxins on nitric oxide synthase activity in
human erythroid K-562 cells.
AB - Because several stimuli of microbial origin enhance the activity of nitric oxide
synthase (NOS) in human cells of the myeloid lineage, we decided to investigate
whether cellular damage induced by Aspergillus terreus mycotoxins could be
associated with an increase in NOS activity. A pool of mycotoxins rather than
individual toxins was tested so that the natural conditions could be mimicked. In
the present study, we report that a crude extract of A. terreus induces cellular
damage and increases NOS activity in K-562 cells, an erythroleukaemic cell line
in which NOS is particularly active. The specificity of this association was
further investigated by using NOS inhibitors and by comparing, in the same
cellular model, the effects of the extract with the activity of other microbial
toxins of a defined mechanism of action. Canavanine, an inhibitor of NOS,
significantly reduced cell death in the presence of the extract, suggesting that
cellular damage, induced by the mycotoxins of A. terreus is at least in part
mediated by NOS activity. Moreover, Escherichia coli lipopolysaccharide (LPS),
known to be a potent NOS inducer, increased NOS activity in our experimental
model as well. In contrast, Bordetella pertussis toxin did not show any effect on
NOS activity. The results of this study suggest that NOS may be involved in
mycotoxicoses.
PMID- 10191508
TI - Modulation of surface transferrin receptors in lymphoid cells de novo infected
with human immunodeficiency virus type-1.
AB - To investigate whether transferrin receptor (CD71) expression is affected by
acute HIV-1 infection, three different lymphoid cell lines (MT-4, SUPT-1, H9)
were infected with HIV-1 and tested for surface CD71 expression after different
incubation periods depending on cell survival after infection. We found that
expression of surface CD71 was lower in cells infected with HIV-1 than in
uninfected controls: the timing and extent of this down-modulation depended
apparently on the different susceptibility of the cell lines to HIV-1 infection
and cytopathogenicity. Citrate, a molecule capable of chelating iron, dose
dependently prevented down-modulation of surface CD71 in HIV-1 infected cells as
well as viral cytopathic effects. We conclude that (i) expression of surface
transferrin receptors is down-modulated by acute HIV-1 infection in T lymphoid
cells, that (ii) this cell phenotypic modulation is associated with the
cytopathic effects of the virus, and that (iii) these phenomena are modulated by
iron chelation. These results support the view that iron metabolism may be an
important area for interaction between HIV-1 and human cells.
PMID- 10191509
TI - NADPH-oxidase activity and lipid peroxidation in neutrophils from rats fed fat
rich diets.
AB - In order to investigate the effect of fat-rich diets on neutrophil functions, 21
day-aged rats were fed for 6 weeks with a control diet consisting of a regular
laboratory rodent chow (4 per cent final fat content), a control diet supplied
with soybean oil (15 per cent final fat content), or a control diet supplied with
coconut oil (15 per cent final fat content). Glycogen-elicited peritoneal
neutrophils from rats fed soybean and coconut oil-enriched diets presented a
reduction in spontaneous and PMA-stimulated H2O2 generation relative to
neutrophils from rats fed the control diet. The activity of superoxide dismutase,
glutathione peroxidase and catalase did not change in animals fed fat-rich diets.
In addition, the capacity to generate O2-, spontaneously or in response to PMA,
did not change in neutrophils from animals fed fat-rich diets. Values attained
matched those observed in animals fed the control diet, regardless of the method
used to measure O2-, the superoxide dismutase-inhibitable reduction of cytochrome
c or the lucigenin-dependent chemiluminescence. However, the initial rate of O2-
generation both in resting neutrophils and in PMA-stimulated cells was
significantly reduced when animals were fed with coconut or soybean oil-enriched
diets due, at least in part, to a reduction in the activity of glucose-6
phosphate dehydrogenase. The concentration of thiobarbituric acid reactive
substances, an index of lipid peroxidation, was increased in animals fed both fat
rich diets. This was accompanied by an increase in arachidonic acid content in
these cells. Results presented suggest that lipid peroxidation in neutrophils
from animals fed fat-rich diets may be associated with a consumption of H2O2
yielding more reactive oxygen-derived species such as the hydroxyl radical.
PMID- 10191510
TI - Environmental modulation of the inhibitory action of D-mannoheptulose upon D
glucose metabolism in isolated rat pancreatic islets.
AB - In pancreatic islets prepared from fed rats and incubated at a low concentration
(1.7 mM) of D-glucose, D-mannoheptulose (10.0 mM) virtually fails to affect the
metabolism of the hexose. Likewise, in islets from starved rats, the relative
extent of the inhibitory action of D-mannoheptulose upon D-glucose metabolism is
much more marked at high (16.7 mM) than low (1.7 mM) hexose concentration.
Nevertheless, despite decreasing the metabolism of D-glucose, starvation augments
the sensitivity to D-mannoheptulose in the islets incubated at a low
concentration of the hexose, D-galactose, but not D-fructose, also augments the
inhibitory action of D-mannoheptulose upon D-glucose metabolism in islets
prepared from fed rats and exposed to the low concentration of D-glucose. A
comparable situation prevails in islets exposed to 2-ketoisocaproate. Forskolin,
however, which decreases D-glucose catabolism in the islets from fed rats exposed
to 1.7 mM D-glucose, fails to affect significantly the inhibitory action of D
mannoheptulose on D-glucose metabolism. It is proposed that hexoses transported
by the same carrier as D-glucose and non-glucidic nutrient secretagogues somehow
increase D-mannoheptulose uptake by the islet cells. The latter two conditions
may be operative in islets exposed to a high concentration of D-glucose, this
accounting for the exquisite sensitivity to D-mannoheptulose of glucose
stimulated islets.
PMID- 10191511
TI - Sleep/wake states of preterm infants: stability, developmental change, diurnal
variation, and relation with caregiving activity.
AB - Using time-lapse video, we recorded the sleep/wake states of 95 preterm infants,
born under 1500 g and cared for in three hospitals, for three 24-hr periods at 33
and 35 weeks conceptional age. The videotapes were scored in 5-min epochs for
quiet sleep (QS); active sleep (AS); wakefulness (Wa); bout lengths of QS (QSBL),
AS (ASBL), and waking (WaBL); nursing/caregiving periods (Crgv); bout lengths of
Crgv (CrgvBL); and time out of the crib (OOC). The infants' sleep showed
significant individual differences at each age, over age, and from day to
nighttime. They showed developmental changes in QS, AS, Wa, and QSBL. QS and QSBL
were positively related to caregiving time; ASBL was related to maternal age; and
QS was related to gestational age and birth weight. Thus, very low birth weight
preterm infants show marked stability and developmental change in the
organization of the sleep/wake states from a very early age, and their states are
related to demographic variables as well as temporal measures of caregiving.
PMID- 10191512
TI - Effect of maternal soothing on infant stress response.
AB - The effect of maternal soothing to infant inoculation as well as everyday
distress on infant cortisol and behavioral responses to stress was examined in
two longitudinal samples of 55 and 74 infants, respectively, between 2 and 6
months of age. There was no evidence that maternal soothing was effective in
reducing infants' cortisol or behavioral responses to stress. The absence of this
relation occurred despite evidence for cross-time stability and cross-situation
consistency in maternal soothing. That maternal soothing plays little role in
lowering infant responses to stress leaves open the possibilities that other
maternal behaviors may mediate children's distress or that infant temperament may
be related to infant stress.
PMID- 10191513
TI - Toward a developmental model of child compliance: the role of emotion regulation
in infancy.
AB - The present study examined the relation between early emotion regulation and
later compliance. When infants were 5, 10, and 18 months of age, they
participated in a frustration task. The degree to which they reacted negatively
to the stimuli and the behaviors they used to regulate that response were coded.
Baseline heart rate also was recorded and a measure of cardiac vagal tone (VNA)
was derived. Several tasks (electrode placement, toy clean-up, and test
situation) were administered to elicit compliance/noncompliance when the
participants were 30 months of age. Results revealed that infants who
demonstrated low levels of regulatory behavior were more likely to be
noncompliant as toddlers. Several interaction effects suggested that the
prediction to later noncompliance was also dependent upon the infants' level of
reactivity. Cardiac vagal tone also was related to compliance but in a
contradictory fashion. High VNA was related to noncompliance to toy clean-up,
whereas low VNA was related to noncompliance to electrode placement. The data
provide support for a developmental model of compliance that includes the ability
to regulate emotional arousal.
PMID- 10191514
TI - The relations among body image, physical attractiveness, and body mass in
adolescence.
AB - Body dissatisfaction, a measure of body image, physical attractiveness, and body
mass index were assessed in the same 115 participants at ages 13, 15, and 18
years. Sex differences in body dissatisfaction emerged between 13 and 15 years of
age and were maintained at 18. Over adolescence, girls increased, while boys
decreased, their body dissatisfaction. Body dissatisfaction was weakly related to
others' ratings of the adolescents' physical attractiveness and their body mass
index. The results support the idea that, overall, adolescents' body image has
little to do with how others perceive them, but once developed remains constant
through much of adolescence.
PMID- 10191515
TI - Infants' learning about words and sounds in relation to objects.
AB - In acquiring language, babies learn not only that people can communicate about
objects and events, but also that they typically use a particular kind of act as
the communicative signal. The current studies asked whether 1-year-olds' learning
of names during joint attention is guided by the expectation that names will be
in the form of spoken words. In the first study, 13-month-olds were introduced to
either a novel word or a novel sound-producing action (using a small noisemaker).
Both the word and the sound were produced by a researcher as she showed the baby
a new toy during a joint attention episode. The baby's memory for the link
between the word or sound and the object was tested in a multiple choice
procedure. Thirteen-month-olds learned both the word-object and sound-object
correspondences, as evidenced by their choosing the target reliably in response
to hearing the word or sound on test trials, but not on control trials when no
word or sound was present. In the second study, 13-month-olds, but not 20-month
olds, learned a new sound-object correspondence. These results indicate that
infants initially accept a broad range of signals in communicative contexts and
narrow the range with development.
PMID- 10191516
TI - Lexical form class information guides word-to-object mapping in preschoolers.
AB - We demonstrate that lexical form class information can play a powerful role in
directing the establishment of word-to-object mappings in referentially ambiguous
situations. A total of 144 3- and 4-year-olds heard a novel label, modeled
syntactically as either a proper name or an adjective, for a stuffed animal of a
familiar kind. We then added a second object of the same kind and asked children
(1) to choose one of the two objects as the referent of a second novel label,
also presented syntactically as either a proper name or an adjective, and (2) to
decide whether this second label could also apply to the object they did not
choose. In each of three experiments, preschoolers were most likely to reject two
words for the same object if both words were proper names (as if one dog could
not be both "Fido" and "Rover"). They were significantly less likely to do so if
both were adjectives (as if one dog could be both "spotted" and "furry") or if
one was a proper name and the other was an adjective (as if one dog could be both
"Fido" and "furry"). Information about lexical form class thus contributed
significantly to the formation of linkages between words and objects.
PMID- 10191517
TI - Parents' report of vocabulary and grammatical development of African American
preschoolers: child and environmental associations.
AB - This study examined how child and family factors affect individual differences in
the language development of African American children between 18 and 30 months of
age. Participants were 87 African American children, primarily from low-income
families. Children's vocabulary and grammatical skills were assessed at 18, 24,
and 30 months of age using the short form of the MacArthur Communicative
Development Inventory (CDI), a standardized parent report tool. Standardized
language tests were administered repeatedly between 1 and 3 years of age. Results
showed that children's vocabulary and utterance length grew linearly over time
between 18 and 30 months of age. Children from more stimulating and responsive
homes were reported to have larger vocabularies, to use more irregular nouns and
verbs, and to use longer utterances, in addition to having more rapid rates of
acquisition of irregular forms and longer utterances over time. Girls used longer
utterances than boys and more irregular forms. Girls also had larger vocabularies
in a secondary analysis that eliminated children whose parent report of their
vocabulary was substantially lower than children's scores on a standardized
language test. There are indications that some parents may be under-reporting
their children's early vocabulary and grammatical development, with a high
proportion of the parents reporting their child's 30 month vocabulary and
grammatical development as being at or below the 10th percentile according to the
CDI norms.
PMID- 10191518
TI - Metamemory in children with autism.
AB - Five experiments are reported comparing metamemory abilities in children with
autism, age- and language-matched mentally retarded children, and language
matched young normal controls. The mean language age of the participants in
Experiment 1 was approximately 6 years, in Experiments 2, 3, and 4 approximately
8 years, and in Experiment 5 approximately 9 years. All the children were given
one or more false belief tests. Experiment 1 assessed the children's
understanding that a task variable (list length) and a person variable (age) will
affect their own and others' performances on an immediate auditory-verbal recall
task. Experiment 2 assessed the ability to utilize category cues in a picture
recall task. Experiments 3 and 4 assessed the ability to verbalize strategies
used in a memory span test and in one retrospective and two prospective memory
situations. Experiment 5 assessed the children's knowledge and understanding of
another person's memory. On the basis of available evidence and theory, we
predicted that the children with autism would be impaired on all the metamemory
tasks and that impairment would be associated with failure on tests of false
belief. Our predictions were not supported. The children with autism were not
impaired on any of the metamemory tasks, although they were less likely than
controls to make spontaneous use of memory strategies involving other people.
Unexpectedly few of the children failed the false belief tasks. These results are
discussed in relation to theories concerning primary psychological deficits
underlying autism.
PMID- 10191519
TI - An adoption study of the etiology of teacher and parent reports of externalizing
behavior problems in middle childhood.
AB - Twin studies of externalizing behavior problems in middle childhood and early
adolescence suggest that there is moderate-to-substantial genetic variance and
modest-to-moderate shared environmental variance in these behaviors. The present
study is novel in three ways: it is a sibling adoption study, it employs both
teacher and parent ratings of children's behaviors averaged over five
assessments, and it explores aggression and delinquency separately. The sample
included 78 adoptive sibling pairs and 94 biologically related sibling pairs in
the Colorado Adoption Project. Parents and teachers completed ratings of the
children's externalizing behavior problems at ages 7, 9, 10, 11, and 12 years.
Boys and adopted children were rated as being somewhat higher in externalizing
behavior problems. Sex differences in delinquency were more pronounced in
adoptive than in nonadoptive families. Teachers' ratings showed evidence for
moderate heritability and no shared environment for aggression and showed modest
shared environment for delinquency. Parents' ratings showed evidence for moderate
amounts of heritability and shared environment for both aggression and
delinquency.
PMID- 10191520
TI - Sex differences in the etiology of aggressive and nonaggressive antisocial
behavior: results from two twin studies.
AB - Recent theory and results from twin and adoption studies of children and
adolescents suggest greater genetic influence on aggressive as compared to
nonaggressive antisocial behavior. In addition, quantitative or qualitative
differences in the etiology of these behaviors in males and females have been
indicated in the literature. The Child Behavior Checklist was completed by the
parents of 1022 Swedish twin pairs aged 7-9 years and of 501 British twin pairs
aged 8-16 years. Genetic factors influenced aggressive antisocial behavior to a
far greater extent than nonaggressive antisocial behavior, which was also
significantly influenced by the shared environment. There was a significant sex
difference in the etiology of nonaggressive antisocial behavior. Bivariate
analyses supported the conclusion that the etiologies of aggressive and
nonaggressive antisocial behavior differ for males and females.
PMID- 10191522
TI - Representation of self and socioemotional competence in kindergartners:
differential and combined effects of attachment to mother and to father.
AB - In the present study, we examined the differential predictive power and the joint
or compensatory effects of representations of child-mother and child-father
attachment for children's representation of self and their socioemotional
competence. The representations of attachment were assessed by an attachment
story completion task, completed once for mother and once for father (in
counterbalanced order). Eighty participants (40 boys and 40 girls), aged between
55 and 77 months (M = 5 years 3 months), took place in the study. The
socioemotional competence (peer social competence, disruptive behavior,
anxious/withdrawn behavior, and school adjustment) and behavioral manifestations
of self-esteem were evaluated by the kindergarten teacher. The inner
representation of self (positiveness of self, perceived competence, and social
acceptance) was assessed in a subgroup of 50 children. Results showed that the
relative predictive power of child-mother and child-father attachments differed
according to the domain of child functioning that was assessed. More
specifically, it was found that the child's positiveness of self was better
predicted by the quality of the child-mother attachment representation than by
the quality of the child-father attachment representation. In contrast, the
child's anxious/withdrawn behavioral problems were better predicted by the
quality of the child-father attachment representation than by the quality of the
child-mother attachment representation. With regard to the joint effects of child
mother and child-father attachment, it was found that a secure attachment to one
parent can compensate for or buffer against an insecure attachment to the other
parent. However, the buffering effect was not complete.
PMID- 10191521
TI - The relation between behavior problems and peer preference in different classroom
contexts. Conduct Problems Prevention Research Group.
AB - This study tested two alternative hypotheses regarding the relations between
child behavior and peer preference. The first hypothesis is generated from the
person-group similarity model, which predicts that the acceptability of social
behaviors will vary as a function of peer group norms. The second hypothesis is
generated by the social skill model, which predicts that behavioral skill
deficiencies reduce and behavioral competencies enhance peer preference. A total
of 2895 children in 134 regular first-grade classrooms participated in the study.
Hierarchical linear modeling was used to compare four different behaviors as
predictors of peer preference in the context of classrooms with varying levels of
these behavior problems. The results of the study supported both predictive
models, with the acceptability of aggression and withdrawal varying across
classrooms (following a person-group similarity model) and the effects of
inattentive/hyperactive behavior (in a negative direction) and prosocial behavior
(in a positive direction) following a social skill model and remaining constant
in their associations with peer preference across classrooms. Gender differences
also emerged, with aggression following the person-group similarity model for
boys more strongly than for girls. The effects of both child behaviors and the
peer group context on peer preference and on the trajectory of social development
are discussed.
PMID- 10191523
TI - Developmental patterns in security of attachment to mother and father in late
childhood and early adolescence: associations with peer relations.
AB - This study examined developmental differences in two dimensions of attachment
security (parental availability and child dependency on parents) in late
childhood (N = 274) and early adolescence (N = 267) and their association with
peer relations. Children's perceptions of mother's availability and boys'
perceptions of father's availability did not differ as a function of age.
Dependency on parents, however, decreased with age. Findings highlight the
importance of distinguishing between parental availability and reliance on
parental help when measuring attachment developmentally. Children's reports of
positive friendship qualities and lack of conflict in their best friendships were
related to attachment to both mother and father, whereas the presence of a
reciprocated friendship and popularity were not. Father availability was a
particularly important predictor of lower conflict with best friends. Findings
indicate that the quality of parent-child attachment generalizes primarily to the
quality of children's close peer relations.
PMID- 10191524
TI - Children "tune out" in response to the ambiguous communication style of powerless
adults.
AB - Changes in children's attentional engagement were assessed as a function of their
exposure to "teachers" who differed in perceived power and the communication
style that is associated with perceived power. In Study 1, "teachers" (women
assigned to an instructional role) were selected on the basis of their perceived
power; low-power women were more likely than high-power women to display
communication ambiguity. Children responded to low-power women with low levels of
(1) autonomic orienting (consistent with low attention) and (2) high errors on a
cognitively demanding task (mental arithmetic). Attentional disengagement was
found to be mediated by the ambiguous communication style of low-power adults. In
Study 2, the "teacher" was a confederate who systematically varied the facial and
vocal ambiguity of her instructions. Children showed the lowest levels of
orienting and the highest level of errors when the "teacher" was ambiguous in
both face and voice. Results were interpreted as showing that adult ambiguity
(naturally occurring or experimentally produced) leads to reductions in
children's attentional engagement.
PMID- 10191525
TI - Cognitive moderators of children's adjustment to stressful divorce events: the
role of negative cognitive errors and positive illusions.
AB - This study examined whether children's cognitive appraisal biases moderate the
impact of stressful divorce-related events on psychological adjustment in 355
children ages 9 to 12, whose families had experienced divorce within the past 2
years. Multiple regression indicated that endorsement of negative cognitive
errors for hypothetical divorce events moderates the relations between stressful
divorce events and self- and maternal reports of internalizing and externalizing
symptoms, but only for older children. Positive illusions buffer the effects of
stressful divorce events on child-reported depression and mother-reported
externalizing problems. Implications of these results for theories of stress and
coping, as well as for interventions for children of divorced families, are
discussed.
PMID- 10191526
TI - Conditions underlying parents' knowledge about children's daily lives in middle
childhood: between- and within-family comparisons.
AB - This study examined the correlates of mothers' and fathers' knowledge about the
daily experiences of their firstborn (M = 10.9 years) and secondborn (M = 8.3
years) children in 198 nondivorced, predominantly dual-earner families. Results
revealed between- and within-family differences in knowledge as a function of
mothers' work involvement, sibship composition (i.e., sex, birth order),
children's personal qualities (e.g., temperament), and parents' personal
qualities (e.g., education, gender role attitudes). Mothers' knowledge did not
vary as a function of how much they worked outside the home, but fathers knew
more about their children's activities, whereabouts, and companions when their
wives worked longer hours. Parents knew more about their younger than their older
offspring. Both mothers and fathers knew more about offspring of the same sex
than about opposite-sex children, leading to greater within-family differences in
families with mixed-sex siblings. Perhaps because parental involvement and
monitoring are more "scripted" for mothers than fathers, fathers' knowledge was
more consistently related to their children's characteristics than was mothers.'
PMID- 10191527
TI - Inulin and oligofructose are part of the dietary fiber complex.
AB - Dietary fiber has been defined as the remnants of plant cells resistant to
hydrolysis by human alimentary enzymes. Its main chemical constituents are
hemicelluloses, celluloses, lignin, pectins, gums, and waxes. The U.S. Food and
Drug Administration and the U.S. Department of Agriculture determine compliance
with nutritional labeling regulations for dietary fiber by use of the existing
AOAC INTERNATIONAL methods for total dietary fiber. The above compounds are
readily detected by these methods. However, some oligo- and polysaccharides are
resistant to human alimentary enzymes and do not precipitate in 78% ethanol, the
usual reagent for precipitating dietary fiber in analytical procedures. Some of
these saccharides, termed fructans, are inulin and oligofructose. They possess
many physiological attributes normally associated with dietary fiber. Inulin is a
mixture of oligo- and polysaccharides composed of fructose moieties joined by
beta(2-->1) linkages in linear chains. Almost each chain ends with a glucose
moiety. Oligofructose is a synonym for fructo-oligosaccharides, with fructose
moieties joined by beta(2-->1) linkages, as in inulin. Not all molecules have a
glucose unit, and the chain length is less than 10 units. A method for inulin and
oligofructose was developed and approved official first action by AOAC
INTERNATIONAL in early 1997. It involves extraction of sample and treatment of
the extract with amyloglucosidase followed by fructozyme (Fructozyme Enzyme
Process Division, Novo Nordisk, Novo Industry, Copenhagen, Denmark). The sugars
released in each of the 3 steps are measured by anion-exchange chromatography.
The concentration of fructans is calculated as the difference of sugars, glucose
and fructose, after the enzymatic treatments and the initial sample. The
repeatability standard deviations for inulin and oligofructose ranged from 2.9 to
5.8% and the reproducibility standard deviations ranged from 4.7 to 11.1%. The
method was accepted by AOAC INTERNATIONAL.
PMID- 10191528
TI - Application of overpressured layer chromatography combined with digital
autoradiography and mass spectrometry in the study of deramciclane metabolism.
AB - Overpressured layer chromatography was combined with the highly sensitive and
rapid digital autoradiography (DAR) and mass spectrometry to separate, detect,
and identify 3H- and 14C-labeled deramciclane metabolites in different biological
matrixes. Several minor and major metabolites were separated from plasma and
urine samples. The radioactive metabolites localized by DAR were scraped from the
thin-layer chromatographic plate and transferred to a mass spectrometer for
structure identification. Several metabolites were isolated and characterized,
including hydroxy-N-desmethyl deramciclane, which is described in detail. The
combination of techniques is efficient and has good sensitivity: about 2
micrograms metabolite from a biological matrix was isolated and identified this
way.
PMID- 10191529
TI - Assay of tinidazole in human serum by high-performance thin-layer chromatography-
comparison with high-performance liquid chromatography.
AB - Determination of tinidazole in human serum by high-performance thin-layer
chromatography (HPTLC) is presented. It includes use of 10 x 10 cm plates coated
with silica gel 60 and chloroform-acetonitrile-acetic acid (60 + 40 + 2) as
mobile phase. Quantitation was performed by densitometry at 320 nm. The linearity
(1-10 ng), precision (6%), reproducibility (5%), recovery (96%), and detection
limit (1 mg/L) of tinidazole determination by HPTLC were comparable with
corresponding method parameters by reversed-phase HPLC. A satisfactory
correlation was found between the 2 analytical methods. The procedure was used to
quantitate tinidazole in patient sera.
PMID- 10191530
TI - Determination of glycarbylamide in chicken tissue by high-performance liquid
chromatography.
AB - A high-performance liquid chromatographic (HPLC) method for determining
glycarbylamide (GB) in chicken tissue was developed. GB was extracted with
acetonitrile, followed by solid-phase extraction cleanup using a Bond Elut
cartridge column with neutral alumina. After the extract had been evaporated to
dryness, the residue was dissolved in 1.0 mL 0.1 N sodium hydroxide. Then 1.0 mL
0.1 M potassium dihydrogen phosphate solution was added to it. HPLC separation
was done on a 250 x 4.6 mm id TSK-GEL ODS 80 column with 0.05M potassium
dihydrogen phosphate as the mobile phase. Ultraviolet detection was done at a
wavelength of 260 nm. The calibration curve of standard GB solutions was linear
between 0.16 and 3 micrograms/mL (correlation coefficient, r = 0.999). The
recovery of GB from chicken muscle spiked at 0.8 microgram/g was 88.6 +/- 2.3%
(mean +/- standard deviation, n = 5), and the lower limit of determination was
0.05 microgram/g in chicken muscle.
PMID- 10191531
TI - Molar absorptivities of aflatoxins B1, B2, G1, and G2 in acetonitrile, methanol,
and toluene-acetonitrile (9 + 1) (modification of AOAC Official Method 971.22):
collaborative study.
AB - Four laboratories participated in a mini-collaborative study of AOAC Official
Method 971.22, Standards for Aflatoxins, Thin-Layer Chromatographic Method, to
extend the method to 3 replacement solvents for benzene for calibration of
standard aflatoxin solutions. Triplicate test sample vials, each containing 25
micrograms of the respective aflatoxin for each of the 4 aflatoxins and for each
of the solvents, were prepared and sent to each collaborator. The collaborators
dissolved the aflatoxin in each vial in 2 mL solvent, measured the UV spectrum,
and reported the absorptivity maxima near 350 nm. The concentrations of the
aflatoxins in the test samples were determined by dissolving identical test
samples in benzene-acetonitrile (98 + 2) and following the procedure described in
AOAC Official Method 971.22. These concentrations were, in turn, used to
determine the molar absorptivities in the other 3 solvents (see Table 1). AOAC
Official Method 971.22 has been modified to extend its applicability to 3
replacement solvents for benzene for calibration of standard aflatoxin solutions.
PMID- 10191532
TI - Laboratory proficiency testing of aflatoxins in corn and peanuts--a cooperative
project between Thailand and the United States.
AB - The objective of this project was to conduct an aflatoxin proficiency test
program in government, academia, and industry laboratories in Thailand. Aflatoxin
free corn and peanuts and corn and peanuts naturally contaminated with aflatoxins
diluted to approximately 25 micrograms/kg were analyzed. Homogeneity of prepared,
naturally contaminated test samples was checked on multiple replicates. The test
was conducted according to the ISO/IUPAC/AOAC INTERNATIONAL Harmonized Protocol
with z scores indicating laboratory performance. The participants used 3 methods:
enzyme-linked immunosorbent assay, thin-layer chromatography, and the minicolumn.
Of 19 laboratories that reported results for aflatoxins in naturally contaminated
corn, 13 (68%) performed satisfactorily, on the basis of the mean obtained by an
expert laboratory, a calculated target value for standard deviation, and the z
score. Of 21 laboratories that reported results for aflatoxins in naturally
contaminated peanuts, 10 (48%) performed satisfactorily. For aflatoxin-free corn,
6 laboratories reported finding aflatoxins at > or = 10 ng/g, chiefly by the
minicolumn method; for aflatoxin-free peanuts, 1 laboratory reported finding
aflatoxins at > 10 ng/g. Subsequently, a workshop of lectures and laboratory
sessions was conducted to improve performance. A new and simple successive
outlier removal procedure applied to the same data removed the same laboratories
as did the use of z scores.
PMID- 10191533
TI - Performance of sampling plans to determine aflatoxin in farmers' stock peanut
lots by measuring aflatoxin in high-risk-grade components.
AB - Five 2 kg test samples were taken from each of 120 farmers' stock peanut lots
contaminated with aflatoxin. Kernels from each 2 kg sample were divided into the
following U.S. Department of Agriculture grade components: sound mature kernels
plus sound splits (SMKSS), other kernels (OK), loose shelled kernels (LSK), and
damaged kernels (DAM). The kernel mass (g), aflatoxin mass (ng), and aflatoxin
concentration (ng of aflatoxin/g of peanuts) were measured for each of the 2400
component samples. The variabilities associated with measuring aflatoxin mass
(ng) in OK + LSK + DAM, or A(OLD)ng, and in LSK + DAM, or A(LD)ng, and aflatoxin
concentration (ng/g) in OK + LSK + DAM, or A(OLD)ng/g, and in LSK + DAM, or
A(LD)ng/g, were determined. The variance associated with measuring aflatoxin in
each of the 4 combinations of components increased with aflatoxin, and functional
relationships were developed from regression analysis. The variability associated
with estimating the lot concentration from each of the 4 combinations of
components was also determined. The coefficients of variation (CV) associated
with estimating the aflatoxin for a lot with aflatoxin at 100 ng/g were 90, 86,
94 and 96% for aflatoxin masses A(OLD)ng and A(LD)ng and aflatoxin concentrations
A(OLD)ng/g and A(LD)ng/g, respectively. The performance of aflatoxin sampling
plans using the combination of aflatoxin masses in OK + LD + DAM and LD + DAM
components was evaluated with a 2 kg test sample and a 50 ng/g accept/reject
limit.
PMID- 10191534
TI - Preparation of Standard Reference Material 2383 (Baby Food Composite) and use of
an interlaboratory comparison exercise for value assignment of its nutrient
concentrations.
AB - The preparation of the recently released Standard Reference Material (SRM) 2383
Baby Food Composite and the process used for value assignment of nutrient
concentrations are reported. SRM 2383 can be used as a control material when
assigning values to in-house control materials and when validating analytical
methods for measuring proximates, vitamins, and minerals in baby food and similar
matrixes. The SRM was prepared as a commercial baby food would be prepared, with
the same ingredients. The Certificate of Analysis for SRM 2383 provides assigned
values for concentrations of proximates, vitamins, and minerals for which product
labeling is required by the Nutrition Labeling and Education Act of 1990. These
assigned values were based on measurements by the National Institute of Standards
and Technology (NIST) and/or collaborating laboratories. Assignment of analyte
concentrations based solely on analyses by collaborating laboratories is
described in this paper. Certified values are provided for retinol, tocopherols,
and several carotenoids including total beta-carotene; the certification of and
methodology used for measurement of these analytes is discussed in a companion
paper (this issue, page 288). Reference values are provided for solids, ash, fat,
nitrogen, protein, carbohydrate, calories, vitamin B1, vitamin B2, vitamin B6,
niacin, biotin, calcium, phosphorus, magnesium, manganese, iron, zinc, copper,
sodium, potassium, and chloride. Reference values for additional carotenoids are
reported in the companion paper (this issue, page 288). Information values are
provided for iodine, selenium, molybdenum, vitamin D, vitamin B12, folic acid,
pantothenic acid, choline, inositol, sugars, total dietary fiber, and 3 classes
of fats.
PMID- 10191535
TI - Value assignment of retinol, retinyl palmitate, tocopherol, and carotenoid
concentrations in Standard Reference Material 2383 (Baby Food Composite).
AB - In 1997, the National Institute of Standards and Technology (NIST) released
Standard Reference Material (SRM) 2383 Baby Food Composite. This SRM can be used
as a control material when assigning values to in-house control materials and
when validating analytical methods for the measurement of proximates, vitamins,
minerals, and trace elements in baby foods and similar matrixes. The Certificate
of Analysis for SRM 2383 provides certified and reference values for
concentrations of lutein, zeaxanthin, beta-cryptoxanthin, lycopene, alpha
carotene, beta-carotene, delta-tocopherol, gamma-tocopherol, alpha-tocopherol,
retinol, and retinyl palmitate for 2 types of sample preparation--extraction and
saponification. The assigned values were based on the agreement of measurements
made by NIST and collaborating laboratories. The Certificate of Analysis also
provides reference and information values for concentrations of proximates,
minerals, and additional vitamins; assignment of these values is discussed in a
companion paper (this issue, page 276).
PMID- 10191536
TI - Reference values of urinary 3,5,6-trichloro-2-pyridinol in the Italian population
-validation of analytical method and preliminary results (multicentric study).
AB - The interlaboratory validation of analytical procedures for the assay of urinary
3,5,6-trichloro-2-pyridinol (TCP) in the general Italian population is reported.
The determinations were performed by high-resolution gas chromatography (HRGS)
with electron capture detection and HRGS with mass spectrometry (MS) in 2
laboratories. The urine samples were from 42 participants from 3 regions of
Italy. The results were evaluated by interlaboratory quality control. Urinary TCP
concentrations were above the detection limit (1.2 micrograms/L) in 88% of the
population, with a mean detectable concentration [GM (GSD)] of 2.8 (1.9)
micrograms/g creatinine (creat). (GM, geometric mean; GSD, geometric standard
deviation.) The Mann-Whitney U test showed that wine consumption was a
statistically significant variable (p < 0.05) for urinary concentrations of TCP.
Analysis of variance of the logarithm of urinary TCP versus wine consumption and
diet showed a statistically significant fit. The model used explained 30% of the
total variance: wine consumption and diet accounted for 37 and 17% respectively
of the explained variance.
PMID- 10191537
TI - Multiresidue screening of pesticides in foods using retention time locking, GC
AED, database search, and GC/MS identification.
AB - Fruit and vegetable extracts were screened for over 400 pesticides by gas
chromatography with atomic emission detection (GC-AED) and an experimental
database. A technique called retention time locking was used to match GC-AED and
GC with mass spectrometry (MS) retention times to those of the database. Samples
were analyzed for sulfur, nitrogen, phosphorus, and chlorine by GC-AED. Possible
pesticides were suggested by database search and identified by GC/MS. Forty-four
pesticide standards were analyzed to determine the precision of retention time
matching and the accuracy of the database search. Analytical retention times
matched database retention times within 0.32 min. Using elemental criteria, the
database search identified the correct compound for 41 of 44 pesticide standards.
For blind spikes of fruit and vegetable extracts, the database suggested 22 of 26
spiked pesticides as matches. Nineteen were identified by GC/MS. The combination
of retention time locking, GC-AED, database search, and GC/MS can be a powerful
tool for identifying pesticides in a complex matrix.
PMID- 10191538
TI - Arsenic determination in certifiable color additives by dry ashing followed by
hydride generation atomic absorption spectrometry.
AB - The preparations of digested samples of certifiable color additives by dry ashing
and wet digestion for arsenic analysis by hydride generation atomic absorption
spectrometry (AAS) were compared. The dry ashing technique was based on the
preparation used in ASTM D4606-86 for determination of As and Se in coal. The
acid digestion method used nitric and sulfuric acids heated by microwaves in
sealed vessels. The digested color additives were analyzed for As by using
hydride generated from sodium borohydride mixed with the acidified solution on a
flow injection system leading to an atomic absorption spectrometer. Dry ashing
was preferable to wet digestion because wet digestion yielded poor recoveries of
added As. Dry ashing followed by hydride generation AAS gave determination limits
of 0.5 ppm As in the color additives. At a specification level of 3 ppm As, the
precision of the method using dry ashing was +/- 0.4 ppm (95% confidence
interval).
PMID- 10191539
TI - Residues of chlormequat and mepiquat in grain--results from the Danish National
Pesticide Survey.
AB - The objective of the present work was to establish information on chlormequat and
mepiquat residues in grain for human consumption. Chlormequat (2-chloro-N,N,N
trimethylethylammonium, CAS RN 7003-89-6) and mepiquat (1,1-dimethylpiperidinium,
CAS RN 15302-91-7) are plant growth regulators used to stabilize stalks in
cereals. The study was part of the Danish National Pesticide Survey, managed by
the Danish Veterinary and Food Administration. Samples were collected in autumn
1997. Residue contents were determined with a newly developed liquid
chromatographic-tandem mass spectrometric (LC-MS/MS) method for chlormequat
analysis. The method was extended to include mepiquat in the present study.
Quantitation was done by the internal standards method, using mass chromatograms
of the most intense daughter ions of mepiquat (m/z 98), chlormequat (m/z 58), and
[13C]-chlormequat (m/z 61, internal standard). For chlormequat, the overall limit
of detection (LD) was 6 micrograms/kg and the limit of determination (LOD) was 10
micrograms/kg. For mepiquat, LD was 2 micrograms/kg and LOD was 3 micrograms/kg.
Of 77 samples analyzed, 51 contained chlormequat and 11 contained mepiquat. The
highest levels of chlormequat were found in samples of oatmeal (3.76 mg/kg) and
rye (1.08 mg/kg). In 9 rye grain samples containing chlormequat, 5 also contained
mepiquat. However, in all samples analyzed, the residues of chlormequat and
mepiquat were below maximum residue limits.
PMID- 10191540
TI - Pesticide residues in selected food commodities: results from the Danish National
Pesticide Monitoring Program 1995-1996.
AB - The paper presents results of analyses of 4182 samples collected from January
1995 to December 1996 for the Danish National Pesticide Monitoring Program. The
program basis is a random sample control supplemented with a target control. The
objectives of the control are to monitor consumer exposure to health hazards and
to enforce national and European Community regulations. The Danish Veterinary and
Food Administration is responsible for establishing methods, data manipulation,
and evaluation, but actual analyses are performed at 4 regional laboratories. In
addition to a description of the Danish National Pesticide Monitoring Program on
food, the effects of lowering the reporting limits are discussed. Pesticides
included are those in current use as well as chlorinated pesticides like lindane,
DDT, and HCB, occurring in food now primarily as a result of environmental
contamination. Commodities analyzed are fruits, vegetables, cereals, bran, fish,
and animal products such as meat, butter, cheese, fat, and eggs. In fruits and
vegetables, residues were detected in 10% of 2515 samples, with higher incidences
of detection for foreign commodities. Violation rate was 0.6%. In food of animal
origin, low levels of organochlorine pesticides were detected in most fish
samples and in more than half of the animal product samples. However, no results
exceeding maximum residue limits were found. No residues of organophosphorus
pesticides were detected in the 231 meat samples analyzed.
PMID- 10191541
TI - Degradation of parathion methyl on field-sprayed apples and stored apples.
AB - Residue levels of parathion methyl on field-sprayed Granny-Smith apples were
studied. The pesticide was applied according to producer recommendations. Apples
received a single spraying at a rate of 40 g active ingredient/100 L. Residues
were determined with a simple gas chromatographic method. Recovery of parathion
methyl was 88-108%, and the limit of determination was 0.002 mg/kg. Decomposition
of parathion methyl was studied in apples remaining on trees after spraying and
in apples harvested and stored under ambient-temperature, refrigerated-room, and
controlled-atmosphere conditions. During post harvest storage, parathion methyl
degrades more slowly than on apples remaining on the trees. Best-fit curves were
determined, and kinetic equations, rate constants, and half-lives were
calculated. Half-lives found were 8 days for apples on trees, 45 days for apples
stored at ambient conditions, 68 days for apples stored in controlled-atmosphere
room, and 62 days for apples stored in a refrigerated room. Under storage
conditions, levels of parathion methyl residues need a long time to become lower
than the legal limit (0.2 mg/kg).
PMID- 10191542
TI - Determination of selenium in meat products by hydride generation atomic
absorption spectrophotometry.
AB - Wet digestion using a mixture of nitric, sulfuric, and perchloric acids and an
aluminum block digester effectively and rapidly decomposed meat samples for
selenium determination by hydride generation atomic absorption spectrophotometry.
Digestion did not require constant attention by an operator. Selenium recoveries
(range, 94-105%) from National Institute of Standards and Technology standard
reference materials and spiked samples were used to validate method accuracy.
Coefficients of variation (CVs) of repeatability of in-house reference materials
used for precision study were 6.4 and 5.6%, respectively, for seafood mix and
mutton liver. Selenium levels in meat products from Brisbane markets varied
widely: 0.042-0.142, 0.081-0.42, and 0.050-0.198 microgram/g (wet weight)
respectively, for beef, chicken, and pork. Overall, selenium levels in
manufactured meat ranged from 0.041 to 0.189 microgram/g. The levels of selenium
found in this study were generally lower than those reported in Finland but
comparable with those reported in some parts of the United States.
PMID- 10191543
TI - Fast determination of lead and copper in dairy products by graphite furnace
atomic absorption spectrometry.
AB - A rapid and direct procedure for determining lead and copper in dairy products by
electrothermal atomic absorption spectrometry (ETAAS) is described. Samples are
slurried in a medium containing 50% v/v hydrogen peroxide, 1% v/v nitric acid,
0.5% w/v dihydrogen phosphate, and 20% v/v ethanol and directly injected into the
furnace with no previous mineralization. Calibration is performed with aqueous
standards. Limits of determination were 0.4 and 2.4 ng/mL for copper and lead,
respectively. The reliability of the procedure was checked by comparison with the
acid mineralization procedure and by analyzing 3 certified reference milk
samples.
PMID- 10191544
TI - A statistical evaluation of the Youden Matched-Pairs Procedure.
AB - AOAC INTERNATIONAL currently permits investigators to use the Youden Matched
Pairs Procedure to obtain estimates of the method performance indicators
repeatability and reproducibility (S(r) and SR, respectively). This report
explains the statistical model assumptions upon which the procedure is based,
provides validity tests for several of these assumptions, explains conditions
under which Youdens' "precision error" is not consistent with precision estimate
S(r) or SR as defined by AOAC INTERNATIONAL, and indicates when precision
estimates based on the procedure should be interpreted with caution or should not
be used.
PMID- 10191545
TI - Repeatability and reproducibility of germicide tests: a literature review.
AB - The results of a quantitative antimicrobial assay can be summarized by the log
reduction value. For an assay to be proposed as a standard method, it is usually
necessary to conduct a collaborative study to demonstrate that the repeatability
and reproducibility standard deviations (SDs) of the log reduction values are
sufficiently small. It is not clear, however, precisely how small those SDs
should be. This paper describes the results of a literature review conducted to
determine the range of repeatability and reproducibility SDs for standard
quantitative antimicrobial assays. The underlying premise is that, for an assay
to have been accepted as a standard method, its repeatability and reproducibility
SDs must have been sufficiently small. This premise implies that the
repeatability and reproducibility SDs of standard assays establish de facto
guidelines for acceptability. The survey comprised papers where the SDs could be
extracted directly or where they could be calculated from accessible data. Papers
describing suspension tests as well as hard surface tests were included. For the
standard antimicrobial assays reviewed, repeatability SDs ranged from 0.25 to
1.21 and the reproducibility SDs ranged from 0.31 to 1.54.
PMID- 10191546
TI - The estimation of the heritability of anthropometric measurements.
AB - The relative contributions of genetic and environmental components in the
variability of anthropometric measurements were studied in 54 twin pairs. Thirty
pairs of monozygotic (MZ) and 24 pairs of dizygotic (DZ) twins were investigated
to estimate the role of genetic, environmental and hereditary factors determining
anthropometric measurements comprising body weight, standing height, sitting
height, knee height, arm span, chest circumference and biiliac diameter. Within
pair variance for all the measurements were significantly smaller (p < 0.05-0.01)
in MZ twins than in DZ twins of both-sex twin group. Within-pair correlations for
those measurements were higher (p < 0.01) in both MZ and DZ twins. Correlation
values were, apparently, higher more in MZ than in DZ twins. Besides, all the
measurements are highly heritable components and heritability estimates ranged
40%-91%. When both MZ and DZ twin pairs of both-sex population were classified,
based on age and sex, into different sub-groups interindividual variabilities
were altered to a certain degrees. These data state that anthropometric
measurements are influenced by genetic factors than environmental factors and
besides, age and sex are possibly associated, to some extent, with the genetic
influence upon anthropometric measurements.
PMID- 10191547
TI - Anthropometric comparison between Japanese and Caucasian American male university
students.
PMID- 10191548
TI - Development of ergometer attachment for power and maximum anaerobic power
measurement in swimming.
AB - The ergometer can be a versatile means of measurement if attachments are
developed for special purposes or if attachment is developed for multi-uses. In
this study, an ergometer attachment for the measurement of power was designed and
the measurement of power and the maximum anaerobic power in swimming was tested.
A rotation drum was attached to one pedal of an ergometer. The rotation of this
drum was synchronized with the rotation of the pedal. One end of a wire for a
traction by a swimmer was connected to the drum. The other end of the wire was
attached to a belt around the waist of a swimmer. The swimmer swam at full
strength, thus causing the drum to rotate. The rotational velocity of the drum
was detected as voltage by a magnetic permanent motor and transformed to wire
tractional velocity; this velocity was equal to swimming velocity. The wire
tension (= load) was controlled by a load adjusting lever of the ergometer. This
wire tension was equal to the load which was added to the swimmer. The power
calculation was based on a curved regression equation approximated from the load
and the velocity. This equation was shown as follows; (P + a) (v + b) = (P0 + a)b
or its development (P + a)v = b(P0 - P) and provided that P: force or load, v:
swimming velocity, P0: maximum tractional force, a and b: constants. This
ergometer attachment made it possible to measure and evaluate the power and the
maximum anaerobic power in swimming with ease and at low cost. Measurement and
evaluation are easily performed using the system, which is just one example of
the possible applications of the ergometer.
PMID- 10191549
TI - Commentary: Emerging and other communicable diseases.
AB - There is an increasing need for integrated, sustainable; and cost-effective
approaches to the management of infectious diseases. For example, an emerging
disease in one country may already be endemic in another country but nearing
elimination in a third. A coordinated approach by WHO towards infectious diseases
is therefore needed that will facilitate more effective support of on-going
efforts for the prevention and control of endemic diseases, intensify efforts
against those diseases targeted for eradication and elimination, and result in
better preparedness and response to new and re-emerging diseases. In order to
meet these challenges, WHO has created a new Programme on Communicable Diseases
(CDS), which will replace the former Division of Emerging and other Communicable
Diseases (EMC). The new Programme will better integrate surveillance, prevention,
control, and research over the whole spectrum of communicable diseases. CDS will
function as focal point for global data and information exchange on infectious
diseases, and inter alia, will reinforce laboratory-based surveillance of
bacterial, viral, and zoonotic diseases to ensure early detection of threats to
international public health. Changes in susceptibility to infectious disease,
increased opportunities for infection, and the ability of microbes to adapt
rapidly will continue to challenge WHO to improve prevention and control of
infectious diseases in the future by establishing strong partnerships with both
the private and public sectors.
PMID- 10191551
TI - [Detecting sleeping sickness: comparative efficacy of mobile teams and community
health workers].
AB - The solution to the problem of human African trypanosomiasis (HAT) first of all
requires improved case detection. Effective tests have been available for a
number of years but the results of medical surveys are still mediocre, mainly
because the populations are poorly mobilized. Those few mobile teams still
visiting villages obtain very low presentation rates. In spite of major
information campaigns among villagers, in Cote d'Ivoire the Institut Pierre
Richet (IPR) and Trypanosomiasis Clinical Research Project (PRCT) teams examined
only 42% (9311) of the 22,300 inhabitants of a disease focus during a
conventional ten-day survey. In the same focus, community health workers
specially trained in sleeping sickness and in the collection of blood samples on
filter-paper examined 73% of the population (15,000 individuals) in less than two
months. Implementation of a sleeping sickness control strategy is restricted to
two types of intervention: either conventional mobile teams which are on hand,
competent and rapidly operational but which fail to carry out exhaustive case
detection, or integration of case detection into primary health care by
entrusting surveillance to the community health workers. This approach requires a
minimum of training but ensures that sentinels are permanently present in the
village communities. By using the community health workers rather than mobile
teams it should be possible to achieve comprehensive monitoring. In operational
terms, the cost of surveillance per person is US$ 0.55 for the mobile teams as
against US$ 0.10 for the community health workers. Integration of HAT case
detection into primary health care is therefore an effective and economical
solution, provided the community health workers are properly supervised and above
all motivated.
PMID- 10191550
TI - Human African trypanosomiasis: a latex agglutination field test for quantifying
IgM in cerebrospinal fluid.
AB - LATEX/IgM, a rapid agglutination test for the semi-quantitative detection of IgM
in cerebrospinal fluid of patients with African trypanosomiasis, is described in
this article. The lyophilized reagent has been designed for field use and remains
stable at 45 degrees C for one year. The test has been evaluated on cerebrospinal
fluid samples from trypanosome-infected and non-infected patients, by comparison
with commercial latex agglutination, radial immunodiffusion, and nephelometry.
All test systems yielded similar results.
PMID- 10191552
TI - Childhood immunization coverage in zone 3 of Dhaka City: the challenge of
reaching impoverished households in urban Bangladesh.
AB - A household survey of 651 children aged 12-23 months in Zone 3 of Dhaka City
carried out in 1995 revealed that 51% of them had fully completed the series of
childhood immunizations. Immunization coverage in slum households was only half
that in non-slum households. Apart from residence in a slum household, other
characteristics strongly associated with the completion of the entire series of
childhood immunizations included the following: educational level of the mother,
number of children in the family household, mother's employment status, distance
from the nearest immunization site, and number of home visits from family
planning field workers. The findings point to the need to improve childhood
immunization promotion and service delivery among slum populations. Two promising
strategies for improving coverage are to reduce the number of missed
opportunities for immunization promotion during encounters between health workers
and clients, and to identify through visits to households those children who need
additional immunizations. In the long run, increasing the educational level of
women will provide a strong stimulus for improving childhood immunization
coverage in the population.
PMID- 10191553
TI - Efficacy of five annual single doses of diethylcarbamazine for treatment of
lymphatic filariasis in Fiji.
AB - Annual single-dose treatments with diethylcarbamazine citrate (DEC) at a dose of
6 mg/kg have been reported effective in reducing microfilariae (mf) rate and
density and applicable to large-scale filariasis control campaigns. However, the
efficacy of such treatments has not been studied quantitatively in relation to
different pretreatment levels of endemicity. This study of 32 villages in Fiji
revealed that five treatments repeated annually steadily reduced village mf rate,
and that the degree of reduction was not influenced by pretreatment levels of mf
density or rate. This indicates that an annual dosage scheme is applicable to
high-endemicity areas. The results also suggest that such treatment affected
juvenile forms of Wuchereria bancrofti and may prevent them from reproducing.
PMID- 10191554
TI - Eradication of schistosomiasis in Guangxi, China. Part 3. Community diagnosis of
the worst-affected areas and maintenance strategies for the future.
AB - Reported are the results of a community-based assessment of maintenance of
schistosomiasis eradication in Guangxi, a large autonomous region of China with a
population of 44 million. Eradication of the disease was achieved in 1989 in
Guangxi but maintenance costs are rising. We focused on three counties that had
the most intense transmission in the past: Binyang, Jingxi, and Yishan. Four
instruments were used: in-depth interviews, focus group discussions, a knowledge,
attitudes and practices survey, and subsequent community feedback. In the past,
schistosomiasis had serious consequences in Guangxi, decreasing work capacity and
restricting marriage and occupational mobility. Since its eradication there have
been clear benefits in terms of increased agricultural output and improved
farming conditions. Personal habits and traditional manual farming activities in
Guangxi would continue to expose a large proportion of the population to
environmental risk if the disease were to return. Ignorance about control
programme achievements is increasing and is related to youth and inexperience.
There was a universal desire in the study counties for more local education about
the history of the programme and about the risk of schistosomiasis returning.
Snail surveillance is considered important, but people are not willing to
volunteer for such work. Our study methods were novel for Guangxi and community
feedback was helpful. Snail checking procedures have been modified to make them
more efficient and no snails have been found since 1992. The animal and human
stool examinations have ceased and vigilance now concentrates on snails and
children (skin tests). The long-term strategy is to make the population
invulnerable to future schistosomiasis transmission if the snail vectors return.
This means continuing education and making the former endemic counties a high
priority for water and sanitation improvements.
PMID- 10191555
TI - Too far, too little, too late: a community-based case-control study of maternal
mortality in rural west Maharashtra, India.
AB - A total of 121 maternal deaths, identified through multiple-source surveillance
in 400 villages in Maharashtra, were prospectively enrolled during 1993-95 in a
population-based case-control study, which compared deaths with the survivors of
similar pregnancy complications. The cases took significantly longer to seek care
and to make the first health contact after the decision to seek care was taken.
They also travelled significantly greater distances through a greater number of
health facilities before appropriate treatment was started. Multivariate analysis
showed the negative effect of excessive referrals and the protective effect of
the following: residing in and not away from the village; presence of a resident
nurse in the village; having an educated husband and a trained attendant at
delivery; and being at the woman's parents' home at the time of illness. Other
significant findings showed that deaths due to domestic violence were the second
largest cause of deaths in pregnancy, that more than two-thirds of maternal
deaths were underreported in official records, and that liveborn infants of
maternal deaths had a markedly higher risk of dying in the first year of life.
This study points to the need for information-education-communication (IEC)
efforts to increase family (especially male) preparedness for emergencies,
decentralized obstetric management with effective triage, and a restructuring of
the referral system.
PMID- 10191556
TI - [Cartography of trachoma in Mali: results of a national survey].
AB - Prior to a campaign to eliminate blinding trachoma, a survey of the prevalence of
the disease was conducted in the seven administrative regions of Mali between
March 1996 and June 1997. In each region (with the exception of Bamako District)
a random sample of thirty clusters was taken from the general population, in
accordance with the principle of probability proportionate to the size of the
communities. All children under 10 years of age and all women over 14 years were
examined. The simplified coding proposed by WHO was used for data gathering. A
total of 15,310 children and 11,530 women were examined. The prevalence of active
trachoma, follicular (TF) or intense (TI), was estimated to be 34.9% among
children under 10 years of age (95% CI: 32.3-37.6). The prevalence of TI showing
the intensity of trachoma was 4.2% (95% CI: 3.5-5.0) among the same children. The
prevalence increased up to the age of 3 years, when it reached 49.2%. The
prevalence of TF/TI was 35.7% among boys and 34.3% among girls. The prevalence of
entropion trichiasis among women over 14 years of age was 2.5% (95% CI: 2.1-2.9),
and 1% had central corneal opacity (95% CI: 0.8-1.3). These prevalences increased
with age, such that 10% of women over 70 years of age had trichiasis. By region
of the country, the prevalence ranged from 23.1% of active trachoma among
children in Segou, to 46.2% in Gao. The prevalence of entropion trichiasis was
0.65% in Gao region and 3.9% in Koulikoro region. This survey allows the trachoma
treatment needs of Mali to be quantified. We estimate that 1.09 million children
under 10 years are carriers of active trachoma and require local or general
antibiotic treatment. If all the under-10-year-olds from all villages where TF/TI
exceeded 20% were to be treated, a total of 2.436 million children would be
involved. A total of 85,000 adults should have surgery to correct trichiasis and
avoid the onset of blindness.
PMID- 10191557
TI - Insecticide-treated nets and treatment service: a trial using public and private
sector channels in rural United Republic of Tanzania.
AB - The Rotary Net Initiative, implemented in Kilombero District, southern United
Republic of Tanzania, allowed us to explore different sales channels for the
distribution of insecticide-treated nets (ITNs) and the insecticide treatment
service in a rural area of very high malaria transmission. Several types of ITNs
were promoted and sold through different channels in the public and private
sector, i.e. hospital pharmacy, mother and child health (MCH) clinic, net
committee, village health workers and retail shops. The ITNs were sold for US$
5.0-9.2, with profit margins of 9-16%. Net treatment cost US$ 0.33, with
commission fees of 75%. Net transport and treatment were partially subsidized.
Some outlets established their own fund by ITN sales. Sales of nets and
treatments were seasonal, and certain net types were preferred. Demand for
insecticide treatment was generally low. Changes in net coverage were assessed in
two villages. A range of outlet features were compared qualitatively. Our
experience supports suggestions that ITN technology should be delivered through
MCH care services and demonstrates that specific promotion and innovation are
necessary to achieve substantial net treatment levels. A large-scale ITN project
in the same area and other ITN studies should lead to better understanding of ITN
implementation at the population level.
PMID- 10191558
TI - A reassessment of the cost-effectiveness of water and sanitation interventions in
programmes for controlling childhood diarrhoea.
AB - Cost-effectiveness analysis indicates that some water supply and sanitation (WSS)
interventions are highly cost-effective for the control of diarrhoea among under
5-year-olds, on a par with oral rehydration therapy. These are relatively
inexpensive "software-related" interventions such as hygiene education, social
marketing of good hygiene practices, regulation of drinking-water, and monitoring
of water quality. Such interventions are needed to ensure that the potentially
positive health impacts of WSS infrastructure are fully realized in practice. The
perception that WSS programmes are not a cost-effective use of health sector
resources has arisen from three factors: an assumption that all WSS interventions
involve construction of physical infrastructure, a misperception of the health
sector's role in WSS programmes, and a misunderstanding of the scope of cost
effectiveness analysis. WSS infrastructure ("hardware") is generally built and
operated by public works agencies and financed by construction grants,
operational subsidies, user fees and property taxes. Health sector agencies
should provide "software" such as project design, hygiene education, and water
quality regulation. Cost-effectiveness analysis should measure the incremental
health impacts attributable to health sector investments, using the actual call
on health sector resources as the measure of cost. The cost-effectiveness of a
set of hardware and software combinations is estimated, using US$ per case
averted, US$ per death averted, and US$ per disability-adjusted life year (DALY)
saved.
PMID- 10191559
TI - Noncommunicable disease management in resource-poor settings: a primary care
model from rural South Africa.
AB - Noncommunicable diseases (NCDs) such as hypertension, asthma, diabetes and
epilepsy are placing an increasing burden on clinical services in developing
countries and innovative strategies are therefore needed to optimize existing
services. This article describes the design and implementation of a nurse-led NCD
service based on clinical protocols in a resource-poor area of South Africa.
Diagnostic and treatment protocols were designed and introduced at all primary
care clinics in the district, using only essential drugs and appropriate
technology; the convenience of management for the patient was highlighted. The
protocols enabled the nurses to control the clinical condition of 68% of patients
with hypertension, 82% of those with non-insulin-dependent diabetes, and 84% of
those with asthma. The management of NCDs of 79% of patients who came from areas
served by village or mobile clinics was transferred from the district hospital to
such clinics. Patient-reported adherence to treatment increased from 79% to 87%
(P = 0.03) over the 2 years that the service was operating. The use of simple
protocols and treatment strategies that were responsive to the local situation
enabled the majority of patients to receive convenient and appropriate management
of their NCD at their local primary care facility.
PMID- 10191560
TI - Antibiotic resistance of nasopharyngeal isolates of Streptococcus pneumoniae from
children in Lesotho.
AB - Villages associated with the Lesotho Highlands Development Agency were randomized
with a bias in favour of larger villages, and children < 5 years of age from
cluster-randomized households in these villages were chosen for the assessment of
antibiotic resistance in pneumococci. Children of the same age group attending
clinics in the capital, Maseru, were selected for comparison. Nasopharyngeal
cultures of Streptococcus pneumoniae from both groups of children were examined
for antibiotic resistance and a questionnaire was used to assess risk factors for
the acquisition of resistant strains. Carriage of penicillin- and tetracycline
resistant pneumococci was significantly higher among 196 Maseru children compared
with 324 rural children (P < 0.05 and P = 0.01, respectively). Maseru children
tended to visit clinics at an earlier age compared with their rural counterparts.
The rural children were less exposed to antibiotics (P < 0.01), were less
frequently hospitalized (P < 0.001), and rarely attended day care centres (P <
0.001). The very low incidence of antibiotic resistance in rural Lesotho and the
higher incidence in Maseru are in stark contrast with the much higher frequencies
found in the Republic of South Africa, many European countries, and the USA.
PMID- 10191562
TI - [Apoptosis in normal and pathological spermatogenesis].
PMID- 10191561
TI - An approach to the problems of diagnosing and treating adult smear-negative
pulmonary tuberculosis in high-HIV-prevalence settings in sub-Saharan Africa.
AB - The overlap between the populations in sub-Saharan Africa infected with human
immunodeficiency virus (HIV) and Mycobacterium tuberculosis has led to an upsurge
in tuberculosis cases over the last 10 years. The relative increase in the
proportion of notified sputum-smear-negative pulmonary tuberculosis (PTB) cases
is greater than that of sputum-smear-positive PTB cases. This is a consequence of
the following: the association between decreased host immunity and reduced sputum
smear positivity; the difficulty in excluding other HIV-related diseases when
making the diagnosis of smear-negative PTB; and an increase in false-negative
sputum smears because of overstretched resources. This article examines problems
in the diagnosis and treatment of smear-negative PTB in high-HIV-prevalence areas
in sub-Saharan Africa. The main issues in diagnosis include: the criteria used to
diagnose smear-negative PTB; the degree to which clinicians actually follow these
criteria in practice; and the problem of how to exclude other respiratory
diseases that can resemble, and be misdiagnosed as, smear-negative PTB. The most
important aspect of the treatment of smear-negative PTB patients is abandoning 12
month "standard" treatment regimens in favour of short-course chemotherapy.
Operational research is necessary to determine the most cost-effective approaches
to the diagnosis and treatment of smear-negative PTB. Nevertheless, substantial
improvement could be obtained by implementing the effective measures already
available, such as improved adherence to diagnostic and treatment guidelines.
PMID- 10191563
TI - [Medical treatment of infertility: therapeutic guide. II. In males].
PMID- 10191564
TI - [Management of a high-grade cervical-vaginal smear].
PMID- 10191565
TI - [Should infertility be treated in couples where one of the partners is HIV
seropositive?].
PMID- 10191566
TI - [For or against infertility treatment in couples where one partner is HIV
seropositive].
PMID- 10191567
TI - [The value of hysteroscopy after repeated implantation failures with in vitro
fertilization].
AB - OBJECT: we attempt to determine the usefulness of uterine re-assessment by
hysteroscopy in women with two unsuccessful IVF-ET attempts. MATERIAL AND METHOD:
This retrospective study concerns seventy-three infertile women who have had a
repeat uterine hysteroscopy after two implantation failures in IVF. RESULTS: In
half the cases, an abnormality was diagnosed. Cervical abnormalities (synechia,
polyp, false passage) and hormono-dependent abnormalities (polyp, hyperplasia,
submucous myoma) were the most frequent findings. The rate of pregnant women
raises to twenty-two percent after treatment of these abnormalities. CONCLUSION:
Regarding our experience, it seems legitimate to perform hysteroscopy in women
who have had two IVF-ET failures before attempting a third procedure.
PMID- 10191568
TI - [Malignant non-seminomatous germinal tumors of the ovary. Experience of the
French Society of Pediatric Oncology. 64 cases].
AB - Ovary seminomatous malignant germ cell tumours are a particular histopathologica
entity. The presence of yolk salk tumor or choriocarcinoma is respectively
correlated with elevation of alpha FP or beta hCG. This markers elevation permits
to assess diagnosis, appreciate response to treatment, and detect relapses. The
study of 64 patients registered in two successive S.F.O.P. protocols (TGM 85-TGM
90) precise indications of surgery, platin-based chemotherapy and results.
Malignant non seminomatous germ cell tumors are separated in not secreting pure
immature teratoma and secreting malignant germ cell tumours. Surgery is essential
for treatment of not secreting pure immature teratoma. Secreting germ cell tumors
are very chemosensitive and surgery must be as conservative as possible in all
cases even metastatic tumour or relapse. If markers are normalized second-look
surgery of secreting malignant germ cell tumours is only necessary in case of
evident residual tumour. However in case of initial chemotherapy, resection of a
pathological ovary is always performed at the end of treatment. These tumours
have a good prognosis: 5-years overall survival and disease-free survival are
85%.
PMID- 10191569
TI - [Therapeutic results of conization with diathermy].
AB - OBJECTIVE: To assess the frequency, histological grade and time interval of
residual and recurrent lesions after loop electrosurgical excision procedure and
to analyse their associated risk factors. METHODS: 288 patients treated by loop
electrosurgical excision procedure between February 1991 and July 1995 were
prospectively included in this study. They agreed to a postoperative cytological
and colposcopic follow-up with a first visit between 3 and 6 months after
excision, a second one between 9 and 15 months and a third one between 24 and 36
months. We used univariate and multivariate analyses to evaluate the association
between clinical variables and residual or recurrent lesions. RESULTS: The
pathologic diagnosis of the specimens included 21 normal cervices (7.3%), 35 CIN
1 (12.2%), 43 CIN 2 (14.9%), 180 CIN 3 (62.5%), 1 adenocarcinoma in situ (0.3%)
and 8 microinvasive cancers (2.8%). The pathologist considered the excision
complete in 244 cases (85%). Among the other 44 patients, 27 had involved
endocervical margins, 17 involved exocervical margins but none had both margins
involved. The mean postoperative follow-up +/- standard deviation was 39 +/- 13
months (range 24-68 months). Treatment failure, defined as the persistence or
recurrence of a cervical lesion, was observed in 20 patients (6.9%) having a
squamous cancer stage IB (n = 1), a CIN 3 (n = 15), an adenocarcinoma in situ (n
= 1) or a CIN 1 (n = 1). In 6 cases the second treatment was performed before the
first cytological and colposcopic visit because of an excision considered
incomplete by the pathologist. Overall 19 out of the 20 treatment failures were
diagnosed within the first two years of the follow-up. The endocervical
localisation of the initial lesion (adjusted RR 13.7; 95% CI 1.3, 150.1; P <
0.05) and incomplete excision (adjusted RR 9.1; 95% CI 3.0, 27.3; P < 0.001) were
the only independent risk factors for treatment failure. CONCLUSION: Residual or
recurrent lesions occurs rarely after loop electrosurgical excision procedure.
They are favoured by totally endocervical lesion and an incomplete excision. With
the association of cytology and colposcopy, 95% of treatment failures can be
detected in the first 2 postoperative years.
PMID- 10191570
TI - [Value of cervical echography in the prediction of premature delivery: literature
review].
AB - Preterm delivery is the leading cause of neonatal mortality. Thus predicting a
preterm delivery is a major obstetrical problem. Endovaginal ultrasonography is a
highly reliable and reproducible method of cervical examination. Unlike with a
digital cervical examination the entire length of the endocervical canal can be
measured. Using this tool, measuring the dilatation of the internal os does not
require the examining finger to be placed inside the endocervical canal.
Therefore, the internal os can be measured even if the external os is closed.
While a digital examination assesses the "dilatability" of the internal os, an
ultrasonography assesses the "true degree of dilatation". In a low-risk
population endovaginal cervical ultrasonography helps rule out a preterm delivery
if cervical length is long enough. It can also detect cervical incompetence. In a
high-risk population, women whose cervix is longer than 30 millimeters can be
identified. These women have over 80% chance to deliver on or after 36 weeks of
pregnancy. Preliminary studies suggest that performing an endovaginal
ultrasonography could decrease the number of false positive clinical diagnosis of
modified cervix and thus, save long, expensive and inefficient hospital stays.
Prospective randomized, controlled studies are needed to confirm these results.
PMID- 10191571
TI - [Aspects of genital tuberculosis in women].
AB - Thirteen cases of genital tuberculosis are reported to make emphasis onto the
difficulties of diagnosis, management and prognosis of the disease. The average
age of the patients is 31 years. Most of them were under 30. The circumstances of
diagnosis were variable. The diagnosis was essentially made thanks to histology.
The evolution was favorable under antibiotics. But clinical sequels as amenorrhea
and infertility are frequent.
PMID- 10191572
TI - [Contraception with levonorgestrel (Norplant) subcutaneous implants. African
experience in Burkina Faso].
AB - The subcutaneous implants from the levonorgestrel (Norplant) has been introduced
in Burkina Faso in September 1992 within the context of a project assisted by a
non-governmental organization (the Population Council). The aim was to reinforce
the family planning programme in Burkina Faso by increasing the number of family
planning methods available for the clients. 4 years after its introduction, we
propose to make a report of our experience in terms of the contraception through
subcutaneous implants in order to better set up an IEC campaign on this method.
Within 4 years, 1,660 users benefitted from that contraceptive method. They were
housewives in 65% of the cases. The age-group of 30-34 years old most used this
method with 28.6%. Multipares most benefitted from this method with 64.3%. In 72%
of the cases, the insertion was made during the premenstrual period. On the
whole, 247 withdrawals have been made before the fourth years for various
reasons. Among those reasons are cycle disorders (60 withdrawals), medical
reasons (53 withdrawals), personal conveniences (47 withdrawals), weight gaining
(14 withdrawals), failures (2 withdrawals). Regarding the side effects, they were
mainly represented by the menstrual cycle disorders such as amenorrhoea,
spotting, hypermenorrhoea in 51% of the cases. A good information and
sensitization campaign should reduce the number of implants withdrawals before
the fourth year of use. Moreover, a perfect knowledge of contraindications is
indispensable before any prescription.
PMID- 10191573
TI - Comparison of cephalometric analysis using a non-radiographic sonic digitizer
(DigiGraph Workstation) with conventional radiography.
AB - Cephalometric analysis conventionally requires radiographic exposure which may
not be compatible with the growing concern over radiation hazards. Recently, the
Dolphin Workstation Imaging System introduced to the dental profession a non
radiographic system, called the DigiGraph Workstation which may be an alternative
to cephalometric radiography. The aims of this study were to compare the validity
and reproducibility of cephalometric measurements obtained from the DigiGraph
Workstation with conventional cephalometric radiographs. The sample consisted of
30 human dry skulls. Two replicated sets of lateral cephalograms were obtained
with steel ball markers placed at the majority of the cephalometric landmarks.
Duplicate tracings prepared from each radiograph were digitized to obtain
cephalometric measurements using the computer software, Dentofacial Planner. For
the DigiGraph Workstation, double sonic digitizations were repeated twice for
each skull, on two occasions. Fifteen angular and one linear measurements were
obtained from both methods and these findings compared using ANOVA, paired t
tests and F-tests. All, except one, cephalometric measurement showed significant
differences between the two methods (P < 0.0001). The DigiGraph Workstation
consistently produced higher values in 11 measurements (mean differences +0.5 to
+15.7 degrees or mm) and lower values in four measurements (mean differences -0.2
to -3.5 degrees). The standard deviations of the differences between readings of
both methods were large (0.4-5.8 degrees or mm). The reproducibility of the
DigiGraph Workstation measurements was lower than that of the radiographic
measurements. The method error of the DigiGraph Workstation ranged from 7 to 70
per cent, while that of radiographic tracings was less than 2 per cent. It was
concluded that measurements obtained with the DigiGraph Workstation should be
interpreted with caution.
PMID- 10191574
TI - Morphological changes in periodontal mechanoreceptors of mouse maxillary incisors
after the experimental induction of anterior crossbite: a light and electron
microscopic observation using immunohistochemistry for PGP 9.5.
AB - Ruffini nerve endings (mechanoreceptors) in the periodontal ligament (PDL) of
mouse incisors were examined to elucidate whether experimentally-induced
crossbites cause any changes or abnormalities in their morphology and
distribution. Anterior guiding planes were attached to the mandibular incisors of
3-week-old C3H/HeSlc mice. At 3 days and 1, 2, 4, 6, and 8 weeks post-attachment
of the appliance, the mice were sacrificed by perfusion fixation. Frozen sagittal
cryostat sections of the decalcified maxillary incisors were processed for
immunohistochemistry of protein gene product 9.5, followed by histochemical
determination of tartrate-resistant acid phosphatase activity to reveal sites of
alveolar bone resorption. Despite the absence of bone resorption within the
lingual PDL of control mice, distinct resorption sites were seen in the
respective regions of the experimental animals. Unlike the controls, many Ruffini
endings showing vague and swollen contours, with unusually long and pedunculated
micro-projections were observed in the affected lingual PDL of the incisors in
the experimental animals with short-term anterior crossbite induction. Club
shaped nerve terminations with few, if any, micro-projections were observed in
the lingual PDL of experimental animals with long-term induction, as well as in
aged control mouse incisors. Differences in the distribution of Ruffini endings
were also observed. These results indicate that changing the direction of the
force applied to the PDL results in rapid and prolonged changes in the morphology
of Ruffini-like mechanoreceptors.
PMID- 10191575
TI - Arrested eruption of the permanent lower second molar.
AB - The incidence of retention/impaction of the permanent lower second molar (M2inf)
lies between 0.6/1000 and 3/1000. Therefore, the purpose of the present study was
to investigate the craniofacial morphology, the frequency of dental anomalies and
the inclination of the affected M2inf and the adjacent first molar in patients
with arrested eruption of M2inf. The overall goal was to elucidate the aetiology
of arrested tooth eruption and to present the characteristics of these patients
in order to improve diagnosis and treatment planning. Radiographic material
(profile radiographs and orthopantomograms) from 19 patients (nine females and 10
males; 13-19 years of age at the time of referral) were analysed. The ages of the
patients when profile radiographs were taken for cephalometric analysis varied
from 8 to 16 years. The study shows that this group of patients, compared with a
reference group, had an increased sagittal jaw relationship (Class II).
Specifically, the mandibular prognathism was less, the mandibular gonial angle
smaller, the mandibular alveolar prognathism enlarged and the maxillary incisor
inclination less than in the reference group. Furthermore, this group of patients
had a more frequent occurrence of morphological tooth anomalies, such as root
deflections, invaginations, and taurodontism. However, none of the patients with
arrested eruption of M2inf had agenesis of the lower third molar. The study did
not reveal an association between the degree of inclination of the M2inf and that
of the first molar in the same region. The results of this investigation show
that conditions such as the craniofacial morphology and deviations in the
dentition are associated with arrested eruption of M2inf. Therefore, it is
important to evaluate these conditions in future diagnosis and treatment planning
of patients with arrested eruption of M2inf.
PMID- 10191576
TI - Ectopic eruption of the maxillary canine quantified in three dimensions on
cephalometric radiographs between the ages of 5 and 15 years.
AB - The eruption paths of 20 ectopic maxillary canine teeth (10 right, 10 left) were
measured in three dimensions on annual lateral and depressed postero-anterior
cephalometric radiographs of 15 patients between the ages of 5 and 15 years and
compared with the eruption of normal canines. It was found that between the ages
of 8 and 12 years ectopic canines on the left side moved more anteriorly than the
normally erupting canines and the same was true of the right canines between the
ages of 7 and 12 years. While the ectopic canines moved occlusally, their
vertical movement was less than normal which accounts for the clinical finding
that canines are impacted in the palate at a high level. The average palatally
ectopic canine always moves palatally, and never shares in the buccal movement
shown by normally erupting canines between the ages of 10 and 12 years. It was
interesting to find that the differences between growth of normal and ectopic
canines in the lateral plane of space are present as early as 5-6 years.
PMID- 10191577
TI - The length and eruption rates of incisor teeth in rats after one or more of them
had been unimpeded.
AB - The eruption rate and length of all four incisor teeth in rats were measured
under ether anaesthesia by recording the position of marks on their labial
surfaces at 2-day intervals, using calibrated graticules in microscope eyepieces.
The rats were divided into four groups and either a lower, an upper, both a lower
and an upper, or no incisors were unimpeded. This paper describes the changes
when the unimpeded incisors returned to the occlusion. Neither the unimpeded nor
the impeded incisors simply returned to control values immediately the period of
unimpeded eruption ended, but showed transient changes in their lengths and
eruption rates. The results confirm that eruption rates are determined by the sum
of the lengths of the lower and upper incisors, rather than by their own lengths,
with longer teeth erupting more slowly. Specifically, restoring the bevel to the
incisors did not slow their eruption below normal impeded rates. The slowing of
the eruption of the longer of two adjacent incisors was related to the length
differences of the incisors in the same jaw, not to the sum of the differences in
both jaws. Contact with the contralateral incisor in the opposite jaw slowed the
eruption of an incisor more than contact with the ipsilateral incisor.
PMID- 10191578
TI - Histological and histochemical quantification of root resorption incident to the
application of intrusive force to rat molars.
AB - This study was conducted to investigate the nature of root resorption resulting
from intrusive forces applied to the rat lower molars, by means of histological
and histochemical techniques with tartrate resistant acid phosphatase (TRAP).
Thirty-eight 13-week-old Wistar strain male rats were used. Intrusive force was
created by a fixed appliance which was adjusted to exert an initial force of 50 g
for the duration of 1, 2, and 3 weeks. The degree of root resorption and
distribution of TRAP positive cells were evaluated. On the root surface, the TRAP
positive scores were low in the apical regions. Significant differences in the
scores were found in the inter-radicular region of the roots between the
experimental and control groups for the 2- and 3-week groups. More active
resorption of bone occurred during the experimental period, as denoted by greater
TRAP positive scores on the bone than on the root surface. Root resorption scores
in the apical root region were larger in the 2- and 3-week groups than in the 1
week group. Significant differences in the root resorption scores were also found
between the 1- and 3-week groups in the inter-radicular region, indicating that
intrusive force application of a longer duration may lead to a higher frequency
of root resorption. It is shown that, irrespective of the level of TRAP positive
cells and root resorption scores, the degree of root resorption activity is
higher in the apical root region than in the inter-radicular area. These results
indicate that cellular cementum may be resorbed more easily because of its richer
organic components and low mineralized structure.
PMID- 10191579
TI - Palatal bone support for orthodontic implant anchorage--a clinical and
radiological study.
AB - When maximal anchorage is required during orthodontic treatment, additional aids
are often needed to support the anchoring teeth. While intra-oral aids may be
limited in their anchorage potential, extra-oral anchoring aids are often
rejected by the patients. Endosseous implants may therefore be a valuable
alternative for stable intra-oral anchorage. However, the possibility of using
conventional implants is insufficient, e.g. for treating purely orthodontic
patients with full dentition or where extraction sites are to be closed.
Therefore, the mid-sagittal area of the palate is an alternative insertion site
for the placement of implants for orthodontic anchorage. The limited bone height
in this area inspired this comparison between bone thickness in the implantation
site as verified by probing during the implantation of Straumann Ortho-system
implants, and thickness as measured on the lateral cephalogram. The results
suggest that vertical bone support is at least 2 mm higher than apparent on the
cephalogram. In none of 12 patients was a perforation to the nasal cavity found.
However, in five subjects the implant projected into the nasal cavity on the post
operative cephalogram. These results were supported by the study of the
projections of palate and wires in wire-marked skulls where the wires were placed
bilaterally on the nasal floor and on the nasal crest. It is therefore concluded
that the mid-sagittal area of the palate lends sufficient bony support for the
implantation of small implants (4-6 mm endosseous length, diameter 3.3 mm).
PMID- 10191580
TI - In vitro comparison of the retention capacity of new aesthetic brackets.
AB - Tensile bond strength and bond failure location were evaluated in vitro for two
types of aesthetic brackets (non-silanated ceramic, polycarbonate) and one
stainless steel bracket, using bovine teeth as the substrate and diacrylate resin
as the adhesive. The results show that metallic bracket had the highest bond
strength (13.21 N) followed by the new plastic bracket (12.01 N), which does not
require the use of a primer. The non-silanated ceramic bracket produced the
lowest bond strength (8.88 N). Bond failures occurred mainly between bracket and
cement, although a small percentage occurred between the enamel-cement interface
with the metal and plastic brackets and within the cement for the plastic
bracket. With the ceramic bracket all the failures occurred at the bracket-cement
interface. This suggests that the problems of enamel lesions produced by this
type of bracket may have been eliminated. The results also show that the
enamel/adhesive bond is stronger than the adhesive/bracket bond in this in vitro
study.
PMID- 10191581
TI - Motivation for and satisfaction with orthodontic-surgical treatment: a
retrospective study of 28 patients.
AB - Motivation for starting treatment and satisfaction with treatment results were
evaluated on the basis of replies to a 14-item questionnaire and clinical
examination of 28 orthognathic patients from 6 months to 2 years after treatment.
The most common reasons for seeking professional help were problems in biting and
chewing (68 per cent). Another major reason was dissatisfaction with facial
appearance (36 per cent). Many patients also complained of temporomandibular
joint symptoms (32 per cent) and headache (32 per cent). Women (8/19) were more
often dissatisfied with their facial appearance than men (2/9), but the
difference was not statistically significant. In agreement with earlier studies,
the results of orthognathic treatment fulfilled the expectations of almost every
patient. Nearly 100 per cent of the patients (27/28) were satisfied with
treatment results, although 40 per cent experienced some degree of numbness in
the lips and/or jaw 1 year post-operatively. The most satisfied patients were
those who stated temporomandibular disorders as the main reason for seeking
treatment and whose PAR-index had improved greatly. The majority of the patients
experienced the orthodontic treatment as painful and as the most unpleasant part
of the whole treatment, but all the patients were satisfied with the pre
treatment information they were given on orthodontics. Orthodontic-surgical
therapy should be of a high professional standard technically, but the
psychological aspects are equally important in the treatment protocol. The
professionals should make efforts to understand the patient's motivations for and
expectations of treatment. Patients should be well prepared for surgery and
supported for a long time after to help them to adjust to post-surgical changes.
PMID- 10191583
TI - [Human genetics and noncommunicable diseases].
PMID- 10191582
TI - The crystal growth technique--a laboratory evaluation of bond strengths.
AB - An ex vivo study was carried out to determine differences in the bond strengths
achieved with brackets placed using a crystal growth technique compared with a
conventional acid-etch technique. A solution of 37 per cent phosphoric acid was
used for acid-etching and a commercially available polyacrylic acid gel, Crystal
lok for crystal growth. A heavily-filled composite resin was used for all samples
to bond brackets to healthy premolar teeth extracted for orthodontic purposes.
Polycrystalline ceramic and stainless steel brackets were used and tested to both
tensile and shear failure using an Instron Universal Testing machine. The tensile
and shear bond strengths were recorded in kgF. In view of difficulties
experienced with previous authors using different units to describe their
findings, the data were subsequently converted to a range of units in order to
facilitate direct comparison. The crystal growth technique produced significantly
lower bond strengths than the acid-etch technique for ceramic and stainless steel
brackets, both in tensile and shear mode. The tensile bond strength for stainless
steel brackets with crystal growth was 2.2 kg compared with 6.01 kg for acid
etch, whilst with ceramic brackets the tensile bond strengths were 3.9 kg for
crystal growth and 5.55 kg for acid-etch. The mean shear bond strength for
stainless steel brackets with crystal growth was 12.61 kg compared with 21.55 kg
for acid-etch, whilst with ceramic brackets the shear bond strengths were 7.93 kg
with crystal growth compared with 16.55 kg for acid-tech. These bond strengths
were below those previously suggested as clinically acceptable.
PMID- 10191584
TI - Improving severe malnutrition case management.
PMID- 10191585
TI - Status of antioxidants and other biochemical abnormalities in children with
dengue fever.
AB - During an outbreak of dengue fever in 1996, 66 children between 45 days and 12
years of age with dengue fever and 25 healthy controls were studied for
antioxidants and other biochemical abnormalities. As per World Health
Organization (WHO) criteria, 14 children were classified as having classical
dengue (DEN), 42 with dengue haemorrhagic fever (DHF), and 10 (including three
who died) as having dengue shock syndrome (DSS). Superoxide dismutase (SOD),
glutathione peroxidase (GPX), and albumin (ALB), the three main antioxidants
studied, were found to be abnormal in 96, 94, and 40 per cent of the cases
respectively. The levels for aspartate aminotransferase (AST), alanine
aminotransferase (ALT), creatinine phosphokinase (CPK), total protein (TP), total
cholesterol (CHO), and triglycerides (TGL) were abnormal in 79, 50, 30, 93, and
67 per cent of the cases respectively. Among the different groups of dengue the
abnormalities were more marked in children with DSS than in those with DEN and
DHF, especially with respect to ALB, TP, TGL, AST, ALT, and CPK (p < 0.005). This
preliminary report of dengue confirms the assumption of free radical generation
and alteration in antioxidant status during acute illness. However, to understand
their complex interaction in disease progression and therapeutic utility, further
studies are required.
PMID- 10191586
TI - Epidemic dropsy in the eastern region of Nepal.
AB - Twenty-six persons from five families comprising 34 members residing in different
areas of Saptari district of the eastern region of Nepal developed symptoms of
epidemic dropsy over 6-8 weeks. Seventeen patients were studied during July
August 1996. The age of affected individuals varied from 3 to 75 years. Members
who had not consumed food cooked in mustard oil or who were not residing with the
family were spared. Mustard oil, which was used for cooking, was found to be
contaminated with oil of Argemone mexicana seeds. Sanguinarine was detected in
all mustard oil samples collected from the homes of affected families.
Gastrointestinal symptoms were present in 82 per cent of cases a week or so prior
to the onset of pedal oedema. Pitting oedema of the lower limbs, fever, and
darkening of the skin were the most consistent features, found in all cases.
Other prominent features such as local erythema (82 per cent) and tenderness (88
per cent) of the lower limbs were present in most cases. Two striking features
not previously noted were perianal itching (100 per cent) and severe carditis (35
per cent) with congestive cardiac failure (29 per cent). Other unique features
noted were 'sarcoid' skin changes (18 per cent), bilateral pleural effusion, and
Roth's spots and subhyloid haemorrhages in the fundus in one patient. Other
important findings were anaemia (88 per cent), hepatomegaly (41 per cent),
pneumonia (35 per cent) and ascites (12 per cent). There were no deaths due to
epidemic dropsy. In the majority of cases, oedema, cutaneous changes, and
carditis showed a marked improvement in 2-3 weeks and patients were well after 6
8 weeks of follow-up.
PMID- 10191587
TI - An analysis of individual, household, and environmental risk factors for
intestinal helminth infection among children in Qena Governorate, Upper Egypt.
AB - During 1994 a cross-sectional survey was carried out on a sample representative
of the population in Qena Governorate, Upper Egypt, to investigate the
relationship between intestinal helminthic infection among children and a wide
range of variables (demographic, behavioural, cultural, socioeconomic, and
environmental). Data were collected by direct observation and by administering a
questionnaire to mothers in charge of the household in a sample of 768 households
representative of the entire population in the governorate. A stool sample survey
was conducted at the same time on all children 2-12 years of age living in the
selected households (n = 2657). Diagnosis of intestinal helminths was made on the
basis of the Kato-Katz thick-smear technique. After univariate analyses,
conducted to define associations among individual, familial, and community
variables and prevalence of infection, the relevant variables were included in a
multivariate logistic model to assess the importance of each factor as an
independent determinant of infection. Several factors were independently
associated with increased risk of intestinal helminth infection. In particular,
the age of the child (between 4 and 5 years) (individual), the age of marriage
for the mother (cultural), type of garbage disposal (household), and type of
settlement (environmental) gave the highest predictive value for infection. The
present results are consistent with those of former studies and highlight the
importance of a multisectorial approach in the control of intestinal helminth
infection.
PMID- 10191588
TI - Soil-transmitted helminthic infection and its effect on nutritional status of
adolescent schoolgirls of low socioeconomic status in Sri Lanka.
AB - The prevalence of soil-transmitted helminthic infection, living conditions, and
practices relating to personal hygiene were studied in schoolgirls (age 14-18
years) in both an urban area (n = 383) and a rural area (n = 231) of Sri Lanka.
The impact of helminthic infection on nutritional status was also studied. The
prevalence of Ascaris and Trichuris infection was significantly higher (p <
0.00001) in the urban area than in the rural area and this was associated with
poor living conditions and personal hygiene. In contrast, the prevalence of
hookworm infection was similar in the two areas. Less than 3 per cent of subjects
had moderate or heavy infection. Trichuriasis was the commonest helminthic
infection and was associated with significantly lower serum vitamin A
concentrations than in uninfected subjects. There was no significant difference
in body mass index or haemoglobin concentration between infected and uninfected
subjects. Our results show that even mild infection with Trichuris had adverse
effects on vitamin A status.
PMID- 10191589
TI - Growth and pubertal development in transfusion-dependent children and adolescents
with thalassaemia major and sickle cell disease: a comparative study.
AB - Despite regular blood transfusion and desferrioxamine treatment, growth
impairment and pubertal delay are commonly seen in children and adolescents with
transfusion-dependent thalassaemia and sickle cell disease (SCD). We evaluated
growth parameters and sexual maturation in a large cohort of children and
adolescents with SCD (n = 110) and thalassaemia (n = 72) receiving nearly the
same protocol of transfusion and chelation, and compared them with those for 200
normal age-matched children, 30 children with constitutional delay of growth
(CSS), and 25 children with growth hormone deficiency (GHD). Before transfusion,
haemoglobin concentration had not been less than 9 g/dl in the past 7 years;
desferrioxamine was administered for 7-10 years, including by the intramuscular
and subcutaneous routes, three times or more per week. The height standard
deviation score (HtSDS), growth velocity (GV) (cm/yr), and growth velocity
standard deviation score (GVDSD) of children and adolescents with thalassaemia
and SCD were significantly decreased compared to normal children (p < 0.01).
Forty-nine per cent of thalassaemic patients and 27 per cent of patients with SCD
had HtSDS less than -2, and 83 per cent of thalassaemic patients and 67 per cent
of SCD patients had HtSDS less than -1. Fifty-six per cent of thalassaemic
children and 51 per cent of children with SCD had GVSDS less than -1. The GV of
thalassaemic children was significantly slower than that for children with SCD.
Children with thalassaemia and SCD had HtSDS and GVSDS comparable to those for
children with CSS but higher than those for patients with GHD. Serum ferritin
concentration was correlated significantly with the linear GV in all patients (r
= 0.45, p < 0.001). The bone age delay did not differ among the three groups with
thalassaemia, SCD and CSS, but the delay was significant in the group with GHD.
The mid-arm circumference was significantly smaller in children with thalassaemia
and SCD than in normal children. The triceps skin-fold thickness of patients with
SCD was significantly decreased compared to thalassaemic and normal children. The
upper/lower segment ratio was significantly lower in thalassaemic and SCD
patients than in normal children. In thalassaemic patients between the ages of 13
and 21 years a complete lack of pubescent changes was present in 73 per cent of
boys and 42 per cent of girls. Seventy-four per cent of the thalassaemic girls
had primary amenorrhoea. Girls with SCD aged between 13 and 21 years had markedly
delayed breast development and menarche. Twenty-five per cent of boys with SCD
above the age of 14 years had absence of testicular development. Males with
thalassaemia and SCD who had spontaneous testicular development had significantly
smaller testicular volume than did normal controls. Short children with
thalassaemia and SCD had significantly decreased serum insulin-like growth factor
1 (IGF-1) concentrations compared to children with CSS. Collectively, these data
confirm the high prevalence of impaired growth and pubertal delay/failure in
children and adolescents with thalassaemia and SCD. The aetiology of impaired
growth includes the contributions of lack of pubertal growth spurt due to
delayed/absent puberty, decreased synthesis of IGF-1 which might be secondary to
a disturbed GH-IGF-1 axis and/or under nutrition, probably due to the
hypermetabolic status of these children. It is suggested that newer protocols of
treatment, in addition to optimization of transfusion and chelation requirements,
should increase the caloric intake of these patients and properly manage their
pubertal delay-failure in order to improve their adult height.
PMID- 10191590
TI - Reasons for hospitalization due to abortion and pregnancy termination.
AB - The aim of this study was to identify the reasons for hospitalization associated
with abortion and pregnancy termination among women attending the Maternity Unit
of IMIP, Recife, Brazil. In a case-control study, 230 women who were hospitalized
consecutively between August 1994 and June 1995 due to causes related to
pregnancy termination or abortion were chosen as cases. Four controls per case
were selected randomly out of a total of 920 women who delivered at the same
hospital. For each potential cause considered, the odds ratio (OR) and respective
95 per cent confidence interval (CI) were calculated. Multiple logistic
regression analysis was then used to control for confounders. Among all potential
causes studied, those that showed significant association with pregnancy
termination or abortion were: being single, absence of emotional support from
partner, being a working woman, literacy up to the fourth year of school, failure
of contraceptive method employed, and experience of previous pregnancies,
children, and abortions.
PMID- 10191591
TI - Infant feeding practices in rural Bangladesh: policy implications.
AB - Although breastfeeding is almost universal in Bangladesh, proper breastfeeding is
on the decline due to several factors. To assess the knowledge and practices of
mothers regarding breastfeeding, data were collected from 2105 mothers during May
August 1996 in two rural areas of Bangladesh. The findings show that mothers'
knowledge regarding proper breastfeeding is poor. Among all the women
interviewed, only 12 per cent stated that the first food for newborns should be
colostrum, and 27 per cent knew that exclusive breastfeeding should be given for
at least 5 months. In practice, of the 1878 women who had live births, 10 per
cent gave colostrum only, while the rest gave pre-lacteal feeds to their infants.
Only 15 per cent of the infants were exclusively breastfed at 5 months of age. A
significant relationship was found to exist between knowledge and practice of
giving colostrum. Also, women between 20 and 24 years of age were more likely to
give colostrum as well as to breastfeed exclusively for the first 5 months. Women
who had their deliveries attended by medically trained personnel and those who
already knew about the appropriate duration of exclusive breastfeeding were also
more likely to practice exclusive breastfeeding for the first 5 months. The study
suggests that steps should be taken to strengthen further the ongoing
breastfeeding programme for improving breastfeeding knowledge and practice in
rural Bangladesh.
PMID- 10191592
TI - No evidence of vertical transmission of HTLV-I and HTLV-II in children at high
risk for HIV-1 infection from Sao Paulo, Brazil.
AB - One hundred and seven plasma specimens obtained from children born to HIV-1
infected mothers were tested for the presence of antibody to human T-cell
lymphotropic virus types I and II (HTLV-I and -II) to determine perinatal
transmission of these agents. None of the children in this study were breastfed.
Fifty-five specimens were from HIV-1 infected children, 28 from HIV-1 non
infected children, and in 24 cases the HIV-1 status could not be defined. In
these series, when ELISA screening tests were employed, HTLV antibodies were
detected in 54.5, 17.9, and 37.5 per cent of cases, respectively, given an
overall ratio of 41.1 per cent. Western blot analysis disclosed 17 specimens with
some HTLV reactivity: three were classified as HTLV-I/II, two confirmed as having
a HTLV-I Western blot profile, and the last 12 samples showed reactivity to only
one of the protein (gag or env) components. In 11 out of 17 cases molecular
approaches were used to confirm HTLV infection in children; no case of HTLV-I or
II was detected. In contrast, when 13 specimens of mother-child pairs were
analysed, three mothers' plasma samples which were seropositive were confirmed to
have HTLV infection by PCR analysis; one case of HTLV-I and two cases of HTLV-II
infections were detected. Taking into account the age of the children and their
Western blot profiles, passive maternal antibodies could be detected until the
age of 15 months. Indeed, after the age of 18 months seroreactivity amongst the
children, with ELISA and Western blot assays, suggests the presence of maternal
antibodies that resist degradation and/or antibodies that cross-react with rgp21
or p19 antigens from HTLV, or alternatively, with components of the HIV-1. These
results emphasize the lack of HTLV-I and -II vertical transmission in children at
high risk who are not breastfed.
PMID- 10191593
TI - Signs of severe bacterial infection in neonates.
AB - The objective of this study was to identify a short list of valid signs for the
development of standard case management guidelines for severe bacterial infection
(SBI) in newborn infants, an important cause of neonatal deaths in low-income
countries. The reported and observed signs of 83 sick neonates admitted during 12
consecutive months were recorded. At discharge, 50 cases were classified, using
predefined criteria, as SBI, mostly pneumonia, and 33 as other disease. The
neonates with other diseases were significantly younger than those with SBI. None
of the reported and observed signs, when used alone, had a high sensitivity, an
important feature for a severe disease amenable to effective treatment. The best
sensitivity (74 per cent) was obtained when a doctor observed severe chest
indrawing or fast breathing or 'not looking well'; the specificity was 67 per
cent and the positive predictive value 77 per cent. The sensitivity of reported
difficult breathing and of observed severe chest indrawing, when measured only
for the diagnosis of pneumonia, improved to 77 per cent, with a specificity of 84
per cent and 66 per cent, respectively. Reported fever and the observation that
the neonate was 'not looking well' were the best independent predictors of SBI on
logistic regression analysis. Simple standard case management (SCM) guidelines
based only on reported and observed clinical signs would not identify the
majority of neonates with SBI at primary health care level.
PMID- 10191594
TI - Acute bacterial meningitis in The Gambia: a four-year review of paediatric
hospital admissions.
AB - Over a 4 year period, 1991 to 1994, 420 patients with acute bacterial meningitis
were admitted to a tertiary urban hospital in The Gambia. Organisms were isolated
from the cerebrospinal fluid in 64 per cent of cases. In the neonatal period
Streptococcus pneumoniae was the single most common organism isolated. Amongst
infants and children the two major pathogens were Haemophilus influenzae and S.
pneumoniae. In the first year of life, children with S. pneumoniae meningitis
were younger than those with H. influenzae infection (median age 3 months versus
6 months, p < 0.00003) and they had a higher case fatality rate (37 per cent
versus 17 per cent, p = 0.002). In view of the high case fatality rate, there is
a need to review overall case management. This will include a review of more
effective antibiotics, the possible role of dexamethasone, and the inclusion of
efficacious vaccines against H. influenzae and S. pneumoniae disease.
PMID- 10191595
TI - School mental health screening: a model for developing countries.
AB - Using the experience derived from a screening programme of all school-going
children in the Al Ain District, United Arab Emirates, this article reports on a
cost-effective model that can be used in other developing countries. The need for
training child health and school professionals in identifying mental and
developmental disorders is discussed.
PMID- 10191596
TI - Using nutritional anthopometry to estimate the prevalence of malnutrition in
infants and children.
PMID- 10191597
TI - Therapeutic modalities for G6PD-related jaundice.
PMID- 10191598
TI - The influence of co-morbidity in the use of fast breathing in detecting pneumonia
in children under 5 years of age.
PMID- 10191599
TI - Features of the 1996 cholera epidemic among Nigerian children in Ibadan, Nigeria.
AB - Although cholera is endemic in Nigeria, few studies have highlighted the
morbidity and mortality patterns among Nigerian children suffering from cholera.
We analysed surveillance data from the Cholera Unit in Ibadan, Oyo State during
the period 1 January to 31 December 1996 with a view to identifying
epidemiological features of the 1996 cholera epidemic that occurred in Nigeria.
Three hundred and two children were affected, and this constituted 21.8 per cent
of the total cases seen during this period. Most cases were seen in the period
February to May, but no significant seasonal variation was noted. The
overwhelming majority (95 per cent) of the cases were among residents of the
unplanned, densely populated areas of Ibadan. The case fatality rate was 5.3 per
cent. This study establishes that cholera causes significant morbidity and
mortality and mortality in Nigerian children. This unpleasant situation can be
favourably reversed if urgent attention is paid to the provision of potable water
to the unplanned, densely populated areas of Ibadan city.
PMID- 10191600
TI - [Global situation of TB and its control].
AB - Tuberculosis occupies 4th place among major causes of death, and the number of
new cases is estimated at 7.25 million in 1997, and 99% of TB deaths and 95% of
new TB cases are seen in developing countries. TB had been brought under control
in developed countries by applying modern TB control programme including
chemotherapy, as basic health infrastructure was already well developed, and
their economy can afford cost of control programme including TB drugs. The rapid
decline of TB due to the success of TB control in developed countries had lowered
the concern on TB, thus bought about the reduction in research grant for TB and
difficulty in bringing up successors engaging in TB control. Similar trend was
seen also in developing countries, where TB still remains one of most important
health problems due to poor quality of the programme caused by poorly developed
health infrastructure including man-power, budget and institutions. New obstacles
which hinder the smooth implementation of TB control programme have appeared, and
they are the rapid expansion of global population, the move of population, the
impact of HIV epidemic on TB and the multi-drug-resistant TB (MDRTB). The growth
of population automatically increases the number of TB cases and gives heavier
burden for TB control. TB has moved from developing to developed countries with
the move of the population, and currently approximately half of new TB cases in
developed countries is occupied by foreign born patients. Among several
opportunistic infections seen in AIDS cases, TB comes out first as the virulence
of tubercle bacilli is much higher than the other germs causing opportunistic
infections. The pathogenesis of TB changes markedly among HIV positives, and the
incidence becomes much higher, and the time interval from the primary infection
to the disease, and that from the detection of the disease to death without any
effective treatment are shortened, and the fatality rate becomes much higher.
Because of the atypical clinical picture, attenuated tuberculin sensitivity and
high incidence of side-effects of TB drugs, in particular thiacetazone, clinical
management of HIV positive TB is much more difficult than ordinary TB. MDRTB is
produce by the bad quality of TB control, and by improving treatment completion
rate as well as the cure rate, decline in the prevalence of drug resistance, both
primary and acquired, could be expected together with the decline of TB itself.
WHO has made a great challenge with TB after the nomination of Dr Kochi to chief
medical officer, TUB in 1989. Currently, Global TB Programme (GTB) is promoting
so-called DOTS strategy of TB control, consisting of the commitment of the
government to give high priority to TB control, passive case-finding with sputum
smear examination by microscopy, directly observed treatment by standardized
short-course regimen of chemotherapy, well-organized logistics for TB drugs, and
the provision of reporting and monitoring system of TB including the evaluation
of treatment outcome by cohort analysis. Marked achievements have been obtained
in several countries introduced DOTS strategy. Japan is asked to intensify its
efforts in international cooperation in TB control.
PMID- 10191601
TI - [Parameters relating to the development of residual pleural thickening in
tuberculous pleurisy].
AB - To identify predictive parameters for the development of residual pleural
thickening in tuberculous pleurisy, we investigated 58 tuberculous pleurisy
patients retrospectively who could be followed up until their chest roentgenogram
no longer changed. The patients were divided into the following three groups
according to the final configuration of pleural space: group I costphrenic angle
(C-P angle) of the affected side was completely or almost completely recovered
(20 cases), group II C-P angle became dull (20 cases), group III pleural
thickening of > 2 mm remained in the lateral chest wall above the diaphragmatic
dome level (18 cases). Differences of the clinical, chest roentgenographic and
laboratory data were compared between these three groups. There were no
differences between groups I and II in all of the parameters compared, while
there were some differences between groups I and/or II and group III. The mean
age of group III (51.1 +/- 18.1 y.o.) was significantly higher than that of group
I (40.7 +/- 18.6 y.o.) and group II (34.7 +/- 14.7 y.o.) (p < 0.05 and p < 0.005
respectively). Glucose level in pleural fluid of group III (32 +/- 31 mg/dl) was
lower than that of group I (96 +/- 13 mg/dl) and group II (86 +/- 21 mg/dl) (p <
0.001, respectively), while the levels of LDH, TP and ADA in pleural fluid were
not different significantly among three groups. BSR (blood sedimentation rate)
and CRP (C-reactive protein) were higher in group III (77 +/- 30 mm/hr and 8.5 +/
4.3 mg/dl) than those in group I (45 +/- 23 mm/hr and 4.1 +/- 5.4 mg/dl) (p <
0.01 and p < 0.05, respectively). The level of albumin in serum was lower and
that of globulin was higher, and consequently that of A/G ratio in group III
(0.78 +/- 0.17) was lower than that of group I (1.15 +/- 0.16) and group II (1.10
+/- 0.22) (p < 0.001, respectively). It should be emphasized that the level of
gamma-globulin was higher in group III irrespective of the presence or absence of
accompanying pulmonary tuberculosis. Most patients more than 40 years old with
serum A/G ratio less than 0.95 belonged to group III (13/15 (87%)) while most of
those with serum A/G ratio more than 0.95 belonged to group I or II (10/11
(91%)). Thus hyper (gamma-) globulinemia and the intensity of inflammatory
reaction in the whole body and in the pleural space are the predictive factors
for the development of residual pleural thickening in tuberculous pleurisy.
PMID- 10191602
TI - [Characteristics of the medical status and living conditions of the homeless
registered as tuberculosis patients in Nagoya City].
AB - An Investigation by questionnaire was conducted in 1996 to know the tuberculosis
(TB) status and living conditions of 50 homeless people registered as TB patients
at one of Nagoya city's 16 health centers. 1. All patients had one or more
symptoms of TB, 64% of them showed positive TB bacilli on smear, and 35.3% of
them had a previous history of TB treatment. However, only 15.2% suspected they
had TB at the onset of symptoms. 2. Main reasons of seeking medical treatment:
28.6% arrived by ambulance after falling down from exhaustion, 25.7% had
consulted with welfare agencies after the onset of symptoms, and 20.0% had been
diagnosed during the treatment of other diseases. 3. When they were admitted to
the hospital they had many concerns: 29.0% loss of income, 19.4% living expenses,
19.4% smoking prohibition, 12.9% admission fee, and 9.7% privacy. 4. They lived
in the following: 42.9% construction camps, 20.0% parks or streets, 17.1% single
room occupancy hotels, 17.1% daily or monthly paid apartments, and 11.4% sauna
baths. 5. Past medical histories of the subjects included 40.6% injuries by labor
accidents, and 25.0% stomach ulcers. Current diseases were 15.6% mental diseases,
15.6% liver diseases, 15.6% diabetes mellitus, and 9.4% alcoholic dependence.
Seventy percent of them consumed alcohol daily (average pure ethanol 125 ml per
day). 6. From the results outlined above, the following proposals relating to TB
control of the homeless should be considered. 1) Educating the homeless as to the
need for a health check when TB symptoms are present. 2) Opening a clinic for the
homeless for easy access to consultation on TB. 3) Directly observed therapy
short-course, for TB in the homeless. 4) Health examination of the employees of
single-room occupancy hotels and sauna baths which are used frequently by the
homeless. 5) A fundamental countermeasure to deal with alcoholic dependency among
the homeless.
PMID- 10191603
TI - [Nontuberculous mycobacterial disease in a general hospital].
AB - Annual incidence of nontuberculous mycobacterial (NTM) disease has been gradually
increasing in the last 10 years in Japan. It is likely to encounter this disease
not only in hospitals specialized in mycobacterial diseases but also in general
hospitals. NTM were isolated from 97 cases between January 1990 and June 1996 at
our hospital. Out of them, 41 patients were diagnosed as NTM disease.
Mycobacterium avium complex (MAC) was the most frequent pathogens (68.3%) and M.
kansasii (22%) was the next. Other pathogens were M. chelonae (4.9%), M.
fortuitum (2.4%) and M. szulgai (2.4%). Results obtained in our hospital were
very similar to the rates which have been reported previously. Patients with MAC
infection showed relatively poor prognosis (eight patients were died out of 28
patients with MAC) in this study compared with the cases reported in previous
papers, and this result could be explained by the severity of illness when they
were admitted to our hospital, the insufficiency of the initial treatment which
should be started with the combined use of three to four antibacterial drugs
including clarithromycin, and to a low dosage of clarithromycin compared with
conventionally adopted dosage. Unlike tuberculosis, human to human transmission
is considered to be negligible in the case of NTM disease, and general hospitals
are able to provide medical care to the patients with NTM disease. Rather, if
general hospitals which are located in the region near to the patients residence
can play more active role in the treatment of NTM disease, it would be more
beneficial to patients requiring long-term follow-up observation. Based on the
result that similar therapeutic results were obtained for infections with other
NTM as reported in previous papers, it is indicated that general hospitals are
able to provide medical care to patients with NTM disease if therapeutic regimens
recommended by specialist are sufficiently understood and applied.
PMID- 10191604
TI - [A case of partial Addison's disease activated with the administration of
rifampicin (RFP)].
AB - The patient was a 76 year-old female with tuberculous tendonitis, treated with
anti-tuberculous drugs including rifampicin (RFP). About two weeks after the
start of RFP, she noticed general malaise and started vomiting, and the
laboratory data showed severe hyponatremia. Because of mild liver dysfunction,
RFP was discontinued and her symptoms gradually improved. Abdominal X-ray and CT
showed swellings and calcifications of adrenal glands bilaterally. Serum ACTH
level was high and cortisole, 17-OHCS, and 17-KS levels were normal. Her response
to rapid ACTH stimulation was blunted significantly. After another trial of RFP,
she started to vomit and complain general malaise again. We diagnosed her as
partial Addison's disease and administered hydrocortisone with RFP. After this
treatment her improvement was rapid. It has been known that RFP causes induction
of enzymes in hepatic microsomes which increase the catabolism of
glucocorticoids. To avoid the risk of adrenal insufficiency, patients with
insufficient adrenal hormone reserve should receive compensatory hydrocortisone
while they are taking RFP.
PMID- 10191605
TI - [Establishment of the quantitative intratracheal infection model of experimental
murine mycobacteriosis].
AB - An intratracheal infection method (IT) of experimental murine mycobacteriosis was
developed for an in vivo study of antimycobacterial agents. IT-model with either
of M. bovis, M. tuberculosis or M. intracellulare exhibited a much more distinct
lung-specific infection than intravenous model (i.v.) with the same dose of
respective mycobacterial strains. Through a series of comparative studies of
benzoxazinorifamycin (KRM) with rifabutin (RBT) or rifampicin (RFP) against
murine tuberculosis models, therapeutic efficacy in the lungs of IT-model was
superior to those of i.v.-model with the same dose of respective drugs (Fig. 2).
In IT-model of M. bovis Ravenel infection, three rifamycin derivatives gave
"distinctive dose-response curves" in the correlation of dose sizes with the mean
survival times or "log10 CFU/lungs reductions". Moreover, based on the results of
"log10 CFU reductions" in different organs in M. tuberculosis Kurono infection
models, "characteristic in vivo activity patterns of each rifamycin" was
obtained. An outline of the new methods for evaluating and characterizing the in
vivo activities of antimycobacterial agents was presented in Fig. 3. This IT
model may be useful not only for the in vivo assessment of antimycobacterial
agents but also for the comparison of virulence among various mycobacterial
strains.
PMID- 10191607
TI - [Management of mycobacteriosis in general hospital without isolation ward for
tuberculosis patients. 1. Diagnosis and treatment of mycobacterial diseases in a
community general hospital].
AB - 94 patients with tuberculosis were identified in a 236-bed community general
hospital without a dedicated tuberculosis ward from June 1986 to February 1998.
69 patients had bacteriological proof of tuberculosis, and the remaining 25 had
clinical evidence thereof. The mean age of all patients was 63.0 years (range: 23
89 years), and the male to female ratio was 2:1. 70 of these cases were admitted.
During this same period of time, the total number of inpatients admitted to the
internal medicine ward reached around 11,000. Excluding 6 cases who were referred
to other hospitals with a tuberculosis ward, the mean duration of hospital stay
of the remaining 64 cases was 51.6 days. Among all 94 cases, 62 had pulmonary
tuberculosis and the other 32 had extrapulmonary manifestations. The latter group
was comprised of 11 with miliary dissemination, 8 pleuritis, 4 osteomyelitis, 2
peritonitis, 2 urinary tract disease, 1 pericarditis, 1 intestinal disease, 1
meningitis, 1 intracranial tuberculoma and 1 genital disease. 3 cases of miliary
tuberculosis with dissemination died with antemortem diagnoses of fever of
unknown origin, pneumonia, and lung cancer with brain metastasis. These 3 cases
illustrate the importance of heightened suspicion of tuberculosis among our
patient population. Referral of patients with positive sputum smears to hospitals
with a tuberculosis ward has occasionally been difficult because of
inaccessibility. Critical comorbid diseases such as chronic renal failure
requiring hemodialysis and malignancies are additional limiting factors to
transfer to such facilities. Therefore, because of the prevalence and extent of
this disease, its myriad clinical presentations, challenges associated with
establishing an early diagnosis, and need to prevent spread to family, other
patients, and staff, dedicated beds for care of tuberculosis in general hospitals
are mandatory.
PMID- 10191609
TI - [Management of mycobacteriosis in general hospital without isolation ward for
tuberculosis patients. 3. Current status of tuberculosis patient care in
university hospitals and general hospitals in Japan].
AB - A recent epidemiological survey has revealed that the incidence of Mycobacterium
tuberculosis (TB) patients in Japan has just increased again after four decades
of decline. In fact, recently there have been numerous reports of TB outbreaks in
health-care facilities. Although our medical school hospital does not have TB
isolation rooms, we have to take care of more than a few TB patients, most of
whom have been transferred from primary care clinics. Although, some of these TB
patients have highly infectious (sputum smear positive), most of them have not
been diagnosed as having highly infectious TB, and therefore, some of their
patients ultimately have to be retransferred to a TB hospital. This indicates
that most physicians in primary care clinics have little knowledge about TB. This
may be partly because of lack of training regarding TB during their medical
student days and residencies. To elucidate current TB patient care status in
university hospitals in Japan, a survey of physicians working in such hospitals
was conducted from September 1997 to January 1998. The survey (questionnaire)
revealed that the majority (76%) of these hospitals do not have TB isolation
rooms. However, these hospitals have to take care of TB patients in their
outpatient clinics and sometimes on their wards because the patients have serious
complications that can not be treated in ordinary TB hospitals. The survey also
showed that for this reason and from an educational point of view, the majority
of the physicians (90%) working in these hospitals thought that university
hospitals should have isolation rooms for such patients. Another questionnaire
revealed that few physicians and nurses in university hospitals have sufficient
experiences in taking care of TB patients. This situation may have been
responsible for producing physicians with little knowledge about TB. Recent
scientific advances have made it possible to construct TB isolation rooms in
ordinary wards by means of separate ventilation systems. Although combatting TB
requires a variety of strategies, appropriate education for both medical students
and residents using isolation rooms in university hospitals may be an effective
means of preventing spread of TB, and this approach may also increase awareness
concerning the prevention of TB outbreaks in hospitals and health-care
facilities.
PMID- 10191608
TI - [Management of mycobacteriosis in general hospital without isolation ward for
tuberculosis patients. 2. The problems of management of the patients diagnosed
pulmonary tuberculosis after admission to the respiratory ward of university
hospital having no an isolation ward for the tuberculous patients].
AB - The management of 28 patients, diagnosed pulmonary tuberculosis by
bacteriological or pathologic findings after the administration to the Koshigaya
Hospital of Dokkyo university school of Medicine from January 1994 through
September 1997, which had no an isolation ward for tuberculosis patients was
analyzed. The mean age of the patients was 50.6 +/- 16.7 (18-85), and the number
of male and female patients was 22 and 6 respectively. The underlying diseases
found in 10 patients were gastric cancer, breast cancer, osteochondrosarcoma,
collagen disease, diabetes mellitus, liver cirrhosis, pneumoconiosis, and
bronchial asthma. Two patients were complicated by a lung cancer. Six of 28
patients showed smear-positive and culture-positive specimens and 22 of 28
patients showed smear-negative and culture-positive specimens. The detection of
mycobacterial DNA in the samples after amplification by the polymerase chain
reaction (PCR) used in 15 patients and was positive for 7 of 15 patients. The
pathological study of the specimens obtained by Transbronchial lung biopsy was
performed for 14 patients. The pathological findings were compatible with
tuberculosis in 7 of 14 patients. The chief complaints of the 11 patients
admitted to the hospital with in 3 days after first visit, were fever in all
patients and in 5 patients with pleural effusion. A few patients showed smear
negative and PCR positive specimens and complicated by lung cancer or other
malignancy, were treated in non isolation ward in the particular case of
emergency evacuation before admission, careful examination such as a tuberculin
test, bacterial examination, and PCR of sputum should be performed in the
patients suspected of having pulmonary tuberculosis. The patients isolating
tubercule bacilli after administration should be transferred to the hospital with
isolated ward for tuberculosis or isolated room in general hospital in the
particular case of emergency evacuation with the greatest care.
PMID- 10191610
TI - [Management of mycobacteriosis in general hospital without isolation ward for
tuberculosis patients. 4. Actual status of the management of tuberculosis
patients in a university hospital without isolation wards for infectious
diseases].
AB - We retrospectively evaluated clinical findings and the actual status of
management of 69 tuberculosis patients admitted to the Fujita Health University
Hospital, a hospital without isolation wards for infectious diseases, between
1991 and 1994. Forty-nine patients were smear-positive and 22 patients were smear
negative and culture-positive. Twenty-five cases (36.2%) were classified as type
II (cavitary) and 29 cases (42.0%) as type III (non-cavitary) according to the
GAKKAI classification of findings on chest X-ray films for pulmonary
tuberculosis. Physicians in charge did not diagnose twenty-four patients (34.8%)
as tuberculosis on admission. Physicians in charge tended not to suspect smear
negative patients of tuberculosis. Most of the patients with cavities on their
chest X-ray films were strongly suspected of tuberculosis on admission, but in
some of them, tuberculosis was not considered at all. Smear-positive patients
with strongly suspected tuberculosis were diagnosed with the disease within three
hospital days, while it took about three weeks in patients who were not
considered as tuberculosis on admission to be diagnosed as tuberculosis. In the
case of smear-negative patients, it took about one month and two months
respectively to diagnose the case as tuberculosis. About half (51.1%) of the
smear-positive patients were admitted and treated in single-bed rooms while 44.7%
were attended in multiple-bed rooms for 11 days before they were transferred to
single-bed rooms. When acid-fast bacilli were detected, 57.4% of the smear
positive patients were transferred to hospitals with isolation wards for
infectious diseases, while the remaining smear-positive patients were treated in
single-bed rooms at the university hospital. About one-third (31.7%) of the smear
negative patients had already left the hospital when specimens were found to be
culture positive for tubercle bacilli. In conclusion, it is utmost important for
physicians to suspect to tuberculosis for the early diagnosis of the disease.
PMID- 10191611
TI - [Management of mycobacteriosis in general hospital without isolation ward for
tuberculosis patients. 5. The management of the patients excreting tubercle
bacilli in a university hospital without isolation ward for tuberculosis].
AB - The Japanese low ruled that the patients excreting tubercle bacilli should be
treated in the isolated ward for tuberculosis. However, it is often difficult to
transfer a patient with serious illness to the isolated ward with insufficient
medical facilities. We investigated retrospectively the manner of the management
of patients excreting tubercle bacilli in the Aichi Medical University Hospital
without the isolation ward for tuberculosis. Materials were 166 patients (0.17%)
out of 97,275 in-patients during 11 years since 1986 to 1996. Respiratory
symptoms were observed in 114 patients (68.7% of 166 patients) on admission. The
initial bacteriological examination was ordered by the attendant doctor within a
week in 93 patients (81.6%) of 114 patients with respiratory symptoms. On the
other hand, a half of the 52 patients without respiratory symptoms on admission
were not examined for sputum bacteriology beyond a week. Anti-tuberculous
treatment was started within a week after positive bacteriological results in 129
patients (77.7% of the whole 166 patients), while the treatment was not carried
out or delayed in 21 patients (12.6%) because of the communication failure of the
bacteriological report to the physicians. Some complications were observed in 101
patients: 21 diabetes mellitus, 20 cancers, 15 hematological disorders, 9
collagen diseases, 6 renal failures on dialysis. Serious illnesses were observed
in 33 patients (20.6% of the 166 patients). Twenty-four patients (73% of the
seriously ill patients) were died of renal failure, pancytopenia, cancer or
respiratory failure. We considered that an isolated room for infectious
tuberculosis with independent air conditioning system in a general hospital or a
educational hospital was very convenient not only to the treatment of the
patients with serious complications, but also to the education and training on
tuberculosis for the medical student or medical stuffs.
PMID- 10191612
TI - [Management of mycobacteriosis in general hospital without isolation ward for
tuberculosis patients. Clinical study on pulmonary tuberculosis associated with
lung cancer patients].
AB - Sixteen of 758 lung cancer in patients (2.1%) were found to have coexisting
pulmonary tuberculosis. Of the above 16 of 758 patients (fifteen men and one
woman), 4 of 214 patients (1.9%) were found from 1988 to 1989, and 12 of 544
patients (2.2%) from 1991 to 1994. In six patients, pulmonary tuberculosis and
lung cancer were found at the same time by clinical work up. In five cases each,
pulmonary tuberculosis preceded lung cancer, and lung cancer preceded pulmonary
tuberculosis, respectively. Ten patients had adenocarcinoma, 4 had squamous cell
carcinoma, and one each had large cell carcinoma and small cell carcinoma,
respectively. Five patients were in stage "II", one in "IIIa", two in "IIIb", and
eight in "IV" of clinical stage of lung cancer. As regards extent of pulmonary
tuberculosis, one patient was in category "II" of the classification of the
Japanese Society for Tuberculosis, 13 were in "III", and two were in "IV". Among
544 lung cancer patients from 1991 to 1994, 9 of 151 patients (6.0%) with a past
history of pulmonary tuberculosis, had active pulmonary tuberculosis, and 3 of
393 patients (0.8%) with no history of pulmonary tuberculosis, had active
pulmonary tuberculosis (statistically significant; p < 0.005). Five smear
positive patients were transferred to a tuberculosis hospital or a tuberculosis
ward, and the remaining 11 patients were treated in isolation in the ward where
they were. The efficacy of anti-tuberculous chemotherapy was almost comparable to
that in patients without lung cancer. However, prognosis was poor, in line with
that of lung cancer. Main discussion was devoted to the reason why the incidence
(in association with tuberculosis) of adenocarcinoma exceeded that of squamous
cell carcinoma in our present study at variance with the studies of other
investigators.
PMID- 10191613
TI - [Sodium azide: a review of biological effects and case reports].
AB - This report reviews the biological effects and case reports of suicidal or
accidental ingestion of, and occupational exposure to sodium azide. Ingested
doses of sodium azide were estimated for the 6 survival and 4 fatal cases
studied. The lowest dose among survival cases was 5-10 mg. The patient reported
headache, sweating, and faintness within approximately 5 minutes of ingestion.
Four victims ingested 20 to 40 mg and recovered within 2 hours. However, a man
who took 80 mg reported chest pain for 6 months after ingestion. The smallest
doses among fatal cases were 0.7-0.8 g for women and 1.2-2 g for men. All victims
suffered from hypotension, tachycardia, hyperventilation, diaphoresis, vomiting,
nausea, and diarrhea. There is no antidote for sodium azide. Detoxicants for
cyanide such as sodium nitrite or thiosulfate were tried, but were unfortunately,
ineffective. Sodium nitrite may worsen the hypotension caused by sodium azide,
and is not recommended. Occupational exposure to sodium azide is thought to be
common, however, fatal exposure is rare. NIOSH "Recommended Exposure Limits" for
sodium azide is 0.3 mg/m3.
PMID- 10191614
TI - [A study on the factors affecting friendship with HIV-infected students in high
school: from the survey of AIDS related knowledge, information sources and
attitudes in 1989 and 1992].
AB - To clarify the factors affecting the friendship with human immunodeficiency virus
(HIV)-infected persons, a self-reported questionnaire study was conducted in two
high schools in Tokyo in 1989 and 1992. A complete set of responses was obtained
from 541 (98%) and 517 (99%) students in 1989 and 1992, respectively. The
following results were obtained: 1) The proportion of the students who received
information on HIV/acquired immunodeficiency syndrome (AIDS) from school teachers
in 1992 was higher than that in 1989 for both males and females. Similarly, for
both males and females, the proportion of students with correct knowledge on HIV
transmission was significantly higher in 1992. The proportion of the students who
intended to have a friendship with a hypothetical HIV-infected classmate or close
friend in 1992 was significantly higher. 2) The results of multiple logistic
regression analysis indicated that such factors as having more correct knowledge
on HIV transmission and considering the confidentiality of persons with HIV/AIDS
were significantly related to having friendship with a hypothetical HIV-infected
classmate for both 1989 and 1992; such factors as being a female and having an
increasing risk of HIV infection were significantly related to the responses
obtained for 1992.
PMID- 10191615
TI - [Cohort study on risk factors for subarachnoid hemorrhage among Japanese men and
women].
AB - PURPOSE: To examine the risk factors for subarachnoid hemorrhage, for few
prospective data have been available on risk factors of subarachnoid hemorrhage
among Japanese. METHODS: A 9.4-year cohort study was conducted on 12,372 men and
women, aged 40-69 years, free of history of stroke in six communities in Japan.
RESULTS: During the follow-up, seventy-one incidents of subarachnoid hemorrhage
occurred. After adjusting for age, serum total cholesterol, body mass index,
history of diabetes mellitus, blood pressure category and drinking category,
current smokers had a significantly increased risk of subarachnoid hemorrhage
compared with 'never-smokers': multivariate relative risk (RR) [95% confidence
interval (95% CI)] = 3.1(1.4-6.9) for women, 1.5(0.4-5.3) for men and 2.7(1.3
5.5)for men and women. Hypertensives had a significantly increased risk of
subarachnoid hemorrhage compared with normotensives: multivariate RR(95% CI) =
3.1(1.6-6.0) for women, 4.3(1.5-12.0) for men and 3.4(2.0-5.9) for men and women.
For men, heavy drinkers (> = 69 g per day ethanol), had a significantly increased
risk of subarachnoid hemorrhage compared with 'never-drinkers': multivariate
RR(95% CI) = 4.3(1.1-16.8). For women, the relationship between heavy drinking
and risk was not examined due to the small number of heavy drinkers (n = 13).
Multivariate RR(95% CI) for men who smoked currently and drank heavily compared
with men who did not smoke currently nor drink heavily was 6.0(1.8-20.1).
Multivariate RR(95% CI) for hypertensive men who drank heavily compared with
normotensive or borderline hypertensive men who did not drink heavily was
13.0(3.9-43.9). Multivariate RR(95% CI) for hypertensive men and women who smoked
currently compared with normotensive or borderline hypertensive men and women who
did not smoke currently was 6.1(1.3-28.7) for men and 6.3(1.4-28.0) for women.
Furthermore, the combination of smoking, hypertension and heavy drinking raised
the risk of subarachnoid hemorrhage substantially: multivariate RR(95% CI) =
17.5(3.4-90.2). CONCLUSION: Smoking and hypertension appeared to increase the
risk of subarachnoid hemorrhage. For men, although the association of smoking
with the risk of subarachnoid hemorrhage was weak compared with women, the
combination of smoking, hypertension and heavy drinking increased the risk
substantially. For women, smoking appeared to be an independent risk of
subarachnoid hemorrhage, and the combination of smoking and hypertension
increased the risk in additive fashion.
PMID- 10191616
TI - [Epidemiological study on association of periodontal disease and total and
differential leukocyte counts].
AB - Periodontal disease is defined as inflammation that is caused by bacteria in
dental plaque. This disease is liable to be a factor contributing to the high
leukocyte count over an extended period. Furthermore, a number of prospective
epidemiologic studies have shown that the leukocyte count is a good predictor of
ischemic heart disease (IHD). However there have been few epidemiological studies
of the relationship between periodontal disease and the leukocyte count. The
purpose of this study was to investigate the relationship between the total and
differential leukocyte counts and oral conditions of Japanese factory workers who
were classified according to their smoking habits. The 1,167 subjects were male
factory workers employed with a chemical factory in Osaka, Japan. The oral
conditions recorded were periodontal status (Community Periodontal Index of
Treatment Needs, CPITN). The relationship between the total and differential
leukocyte counts and the CPITN score of subjects who were classified according to
their smoking habits was investigated in 1996 and 1997. In both the current
smokers and nonsmokers, the subjects with severe periodontal disease, in contrast
to the normal subjects, exhibited total leukocyte, neutrophil and monocyte counts
that were significantly high for 1 year during follow-up studies. The periodontal
disease is shown that causes the total leukocyte and neutrophil counts related to
the development of IHD to remain at a high level.
PMID- 10191617
TI - [The effects of fish supplementation of platelet function, count and metabolism
in healthy Japanese].
AB - To investigate changes in platelet function, count and metabolism following fish
intake among Japanese, we conducted an experimental intervention study of seven
healthy Japanese volunteers (4 males and 3 females) aged 28-58 years. We
supplemented their diets with an approximate daily intake of 200-400 g fish which
is equivalent to about 10 g n3-polyunsaturated fatty acids (about 3.5 g
eicosapentaenoic acid plus 5.0 g docosahexaenoic acid) during the 17 days. The
study continued until the 23rd day after returning to an ad libitum diet. The
proportion of serum n3-polyunsaturated fatty acids increased two-fold on 5th day
and three-fold on 15th day of fish supplementation, but decreased to one and a
half-fold on the 2nd day and returned to the level before fish supplementation on
the 12th day after returning to an ad libitum diet. The proportion of serum n6
polyunsaturated fatty acids decreased by 17% to the level before fish
supplementation on the 5th day, 33% on the 15th day of fish supplementation.
However, the decrease was only 10% on the 2nd day and the proportion returned to
the same level as before fish supplementation on the 12th day after returning to
an ad libitum diet. As a result, the serum n3/n6 polyunsaturated fatty acid ratio
increased four-fold on the 15th day of fish supplementation, and returned to the
baseline level on the 12th day after returning to an ad libitum diet. Platelet
counts decreased and the mean platelet volume increased during fish
supplementation. Both parameters returned to the level before fish
supplementation on the 12th day after returning to an ad libitum diet. The counts
and proportion of large type platelets increased significantly during fish
supplementation. Although platelet aggregation by ADP (adenosine 5'-diphosphate)
did not change significantly, platelet aggregation by collagen tended to decrease
during fish supplementation. Platelet factor 4, one of the indices of platelet
activity, decreased significantly during fish supplementation. The mean serum
triglyceride level declined during fish supplementation, but returned to the
level just before fish supplementation on the 2nd day after returning to an ad
libitum diet. The mean plasma fibrinogen level tended to decline during fish
supplementation and remained lower until the 12th day after returning to an ad
libitum diet. Habitual fish intake may attenuate the development of
atherosclerosis and prevent ischemic heart disease through suppression of
platelet activity, and by reducing platelet counts and serum triglyceride levels.
PMID- 10191618
TI - [Smoking behavior of nurses in Mie Prefecture, Japan].
AB - Nurses who work in hospitals and clinics belonging to a regional medical
association in Mie prefecture were surveyed regarding their smoking behavior and
several related factors. The results are summarized as follows: 1) Smoking
prevalence in male and female nurses was 75.5% and 14.6% respectively. In the
present study the rate of female nurses was almost equal to results reported in a
national survey. 2) Smoking prevalence was higher among licensed practical nurses
than registered nurses, and it was highest among psychiatric nurses. 3) Smoking
prevalence among hospital and clinical nurses was 15.7% and 9.1% respectively.
Smoking prevalence was lower among clinical nurses, even though, they have a
higher number of licensed practical nurses. Also smoking prevalence was higher in
hospitals with a smaller nursing staff than in hospitals with a larger nursing
staff. 4) Among smokers, 44.5% seriously had attempted to quit smoking, and 34.1%
had considered quitting but never tried. Therefore, the results suggest the
importance of providing smoking cessation programs for nurses.
PMID- 10191619
TI - [Characteristics of the clients in a geriatric intermediate care facility located
in the suburbs of an urban area and factors related to the discharge destinations
desired by family caregivers].
AB - Among the clients in a geriatric intermediate care facility located in the
suburbs of Osaka and their family caregivers (72 subjects), the characteristics
of the clients and their caregivers, and the discharge destination desired by
their family caregivers were investigated, and the associated factors were
evaluated. 1. Characteristics of the clients. The clients were elderly females
with a low degree of independence, and dementia was observed in about 60% of
them. The clients had a relatively large number of children, but many of them
lived alone before admission. The rate of admission from hospitals was high
(54%), and that of discharge to hospitals was also high (50%). Sixty-seven
percent of the clients stayed for a long duration of over 6 months. 2. Conditions
of the family caregivers. Most of the family caregivers were daughters or
daughters-in-law, and considered themselves to be healthy. Sixty-three percent of
the caregivers had jobs. However, most of the caregivers did not have sub
caregiver. 3. Factors related to the discharge destination desired by family
caregivers. Not many family caregivers (19.4%) wanted them to go back to their
homes after discharge, but their preferred discharge destinations were home
(19.4%), hospitals (55.5%), and nursing homes (25.1%). The caregivers of single
household clients often desired a nursing home as the discharge destination, and
those of the clients from a 2- or 3-generation household often desired a
hospital. The factors related to the discharge destination desired by client's
family caregivers were that the client not show dementia, the job of the
caregiver was a part-time job, there was a sub-caregiver, and the client had the
experience of home public health nursing visits. This study showed, the
percentage of the clients discharged from the geriatric intermediate care
facility to their homes was low, and that of the family caregivers who desired
their home as the discharge destination was also low. However, the results
suggested that leading the discharge destination to the client's home is possible
if social resources are provided such as the use of public health nursing
services.
PMID- 10191620
TI - [A study of air pollution in the smoking hall].
AB - We investigated the air pollution in the student smoking hall from February 1st
in the winter season, and during 8 days in the middle of April in the spring
season. The student smoking hall was in an open, draught location. Moreover, the
concentration of pollutants were measured in three time periods: break, lecture
and lunch times. The pollutants measured were nitrogen monoxide (NO), nitrogen
dioxide (NO2), carbon monoxide (CO), carbon dioxide (CO2), suspended particulate
matter (SPM) and polynuclear aromatic hydrocarbon (PAH). The concentrations of
pollutants measured during the break times were of a relatively higher level than
those during the lecture and lunch times. However, the concentration of
pollutants were not influenced by ventilation operation in the smoking hall,
which is not a closed place. SPM and CO2 concentrations during the break time
were instantaneously investigated above Building Sanitation Standards Management,
Japan (SPM: 0.15 mg/m3, CO2: 1,000 ppm). Especially, the SPM concentration was
recognized to be strongly influenced by tobacco smoke.
PMID- 10191621
TI - [Effect of body positions in human optokinetic nystagmus and optokinetic after
nystagmus].
AB - We determined whether whole body tilt would shift the axis of optokinetic
nystagmus (OKN) and optokinetic-after nystagmus (OKAN) induced by full-field
rotation at 35 degrees/sec. Fifteen normal people were positioned upright or
tilted 30 degrees, 60 degrees or 90 degrees to both sides. Stripes of 5 degrees
were projected on a 10-foot dome around the subject's yaw axis. Each trial lasted
45 sec. The lights were then extinguished, and the subject remained in darkness
for 30 sec, while after nystagmus (OKAN) was recorded. Horizontal and vertical
eye movements were recorded by video-oculography at 60 Hz. Eye position and
velocity data were stored on optic disk cartridge by use of the data acquisition
system. A. OKAN: For the subject in the upright position, the OKN velocity vector
was aligned with both gravity and the subject's yaw axis with two minor
exceptions. When the subject was tilted, a vertical OKN component (VOKN) appeared
in a majority of subjects. For all 15 subjects, the mean angle of the OKN
velocity vector regravity (Vectorg) was 22.6 +/- 7.2 degrees at 30 degrees tilted
position. The Vectorg were 48.5 +/- 10.3 degrees at 60 degrees tilted position,
and 76.4 +/- 12.6 degrees at 90 degrees tilted position. This represented shifts
of the OKN velocity vector from the body axis of 7.4 degrees, 11.5 degrees and
13.6 degrees, respectively. The horizontal OKN (HOKN) gain remained unchanged in
different positions. B. OKAN: The duration of HOKAN and initial slow phase
velocity (SPV) of HOKAN decreased as the body position increased from upright to
30 degrees, 60 degrees and 90 degrees tilted position, respectively. The
incidence and initial SPV of VOKAN and Re-Body did not change as the body
position increased from upright to 30 degrees, 60 degrees and 90 degrees tilted
position, respectively. Thus, VOKN was observed during HOKN as subjects were
tilted and tended to vector to gravity, but VOKAN was not always observed during
horizontal OKAN when subjects were tilted.
PMID- 10191622
TI - [Simultaneous reconstruction of pharyngoesophagus and phonetic shunt following
laryngopharyngoesophagectomy].
AB - Because of its many advantages, free jejunal transfer has gained wide acceptance
for pharyngoesophageal reconstruction after ablative surgery. Because the jejunum
is well vascularized, it facilitates good wound healing, and has a low incidence
of anastomotic insufficiency, fistula formation and stricture. However, voice
rehabilitation in this group of patients can be difficult. Therefore, we
performed primary tracheojejunal shunt operations for voice restoration with
jejunum siphons using Nozaki's method (type 3). In this procedure, after dividing
a section of the jejunum into two segments, the reconstructed
neopharyngoesophagus is anastomosed in a side-to-end fashion to the fabricated
shunt using the other segment of the jejunum, as an "elephant nose shunt" so
called because of its appearance. Voice restoration can be achieved in patients
who undergo laryngopharyngoesophagectomy through these reconstructive procedures.
We performed this surgery for nine hypopharyngeal cancer patients after total
pharyngo-laryngo-esophagectomy. Following placement of the shunt, no special care
was required. Only one patient developed a severe aspiration. No leakage was seen
and the swallowing function was preserved in all patients. Four of nine patients
could speak well following these procedures. A vibratory source is created in the
neoesophagus, above the elephant shunt. During speech production, narrowing of
the inside and vibration of the jejunal mucosa can be observed using a laryngeal
fiber scope. In order to study the acoustical characteristics of shunt speech,
voice analysis was performed in patients with restored phonatory function using
Computerized Speech Lab Model 4300 (KAY). Irregularities of pitch periods in the
voice sample were measured using Jita (the pitch period) and Jitt (relative
evaluation of the pitch) for the very short term (cycle-to-cycle), and PPQ (pitch
period pertubation quotient) for the short term (cycle-to-cycle with a smoothing
factor of 5 periods). Irregularities of the peak-to-peak amplitude were measured
using ShdB (evaluation in dB of the peak-to-peak amplitude) and Shim (relative
evaluation of the peak-to-peak amplitude) for the very short term (cycle-to
cycle), and APQ (amplitude perturbation quotient) for the short term (cycle-to
cycle with a smoothing factor of 11 periods). The pertubation parameters of shunt
speech are larger than normal ones not only in terms of the period but also in
terms of the amplitude. These results are similar to those of laryngeal polyps,
recurrent nerve palsy and esophageal speech. Recovery of phonation using Nozaki's
type 3 method with the elephant nose shunt appears promising for pharyngo-laryngo
esophagectomized patients.
PMID- 10191623
TI - [Role of angiotensin-converting enzyme on bradykinin nasal provocation:
comparison of normal volunteers and allergic subjects].
AB - Nasal allergy is the most common type I allergic disease. During allergic
reaction, chemical mediators may be released from residual cell, and thus,
attract additional inflammatory cells. One mediator implicated in this response
is bradykinin (BK), a potent proinflammatory nonapeptide. This study was designed
to investigate the effects of BK on nasal mucosa, and to determine the role of
angiotensin-converting enzyme (ACE) in BK-induced nasal responses. BK nasal
provocation (100 micrograms) was studied in 7 normal volunteers and 7 patients
with perennial allergic rhinitis. After provoking of BK response, nasal
secretions and saline lavage fluids were collected for analysis of total protein
(a protein secretion marker), albumin (a vascular permeability marker), and
lysozyme (a serous cell marker). In addition, after administering of Captopril 50
mg, a specific ACE inhibitor, the same protocol was performed. In both groups, BK
induced plasma exudation and serous gland secretion. Premedication with captopril
did not alter BK-induced responses in normal individuals. In allergic patients,
captopril enhanced BK-induced vascular permeability, but not glandular secretion.
These results indicate that allergic subjects have nasal hyperresponsiveness to
BK, and that ACE predominantly modulates the vascular permeability of allergic
nasal mucosa. It seems likely that BK may contribute to the expression of nasal
allergic symptoms, and that inhibition of ACE may lead to increased nasal
responsiveness.
PMID- 10191624
TI - [Analysis of serum antibodies to alpha-streptococci in patients with tonsil
related pustulosis palmaris et plantaris].
AB - To determine the systemic immune response to alpha-streptococci (Str. sanguis,
Str. salivarius and Str. mitis) and beta streptococcus (Str. pyogenes T12) in
patients with tonsil related pustulosis palmaris et plantaris (PPP), we measured
serum antibody levels to whole cell body antigens of Streptococcus (Str.)
sanguis, Str. salivarius, Str. mitis or Str. pyogenes by enzyme-linked
immunosorbent assay (ELISA). The serum IgG antibody levels to alpha-streptococci,
Str. sanguis and Str. salivarius were significantly higher in patients with PPP
(n = 44) than in patients with recurrent tonsillitis (RT: n = 25) and in healthy
adults (n = 17). Serum antibody IgG level to Str. pyogenes was not different
among the 3 groups. The IgA antibody levels against any Streptococcus strain were
not different among the 3 groups. The IgM antibody levels to Str. pyogenes were
significantly higher in patients with RT than in patients with PPP. In western
blot analysis, the serum IgG antibodies against 25-27 kDa protein from whole cell
body of Str. sanguis, Str. salivarius and Str. mitis were found more frequently
in patients with PPP than in healthy adults. However, the western blot profile in
Str. pyogenes was not different between PPP and healthy adults. No significant
difference was seen in the western blot profile of IgM or IgM antibodies to any
streptococcal whole cell bodies. These data suggest that systemic hyper immune
response to alpha-streptococci may be present in patients with tonsil-related PPP
and the 25-27 kDa protein of the organism may be the target for this immunologic
abnormality.
PMID- 10191625
TI - [Glutathione and cisplatin resistance in head and neck cancer].
AB - Since glutathione is considered to be an important mediator of cancer cell
resistance to cisplatin-based chemotherapy, we investigated glutathione in head
and neck cancer by both laboratory and clinical investigations. MATERIALS AND
METHODS: Intracellular glutathione concentration was measured in 7 different cell
lines that originated from head and neck cancer and was correlated to their IC50
to cisplatin. Expression of gamma-glutamyl cysteine (gamma-GCS) mRNA was assessed
by in situ hybridization and gamma-glutamyl transpeptidase (GGT) expression was
assessed with immnunohistochemistry of 56 biopsy specimens from 51 clinical
cases. Both these enzymes are important for maintenance of intracellular
glutathione concentration. RESULTS: Intracellular glutathione concentration was
strongly correlated with cisplatin IC50 (R2 = 0.814, P = 0.0012), suggesting that
glutathione plays a major role in cisplatin resistance in head and neck cancer.
High gamma-GCS expression was observed in 27 out of 47 specimens (57%), but the
response rate to chemotherapy (63%) in the high expression group was not
significantly different to the low expression group (P = 0.20). High GGT
expression was observed in 32 out of 53 specimens (60%), but the response rate in
the high GGT group was not significantly different to that of the GGT group.
CONCLUSION: Although intracellular glutathione plays an important role in
resistance to cisplatin in head and cancer cell lines, we failed to prove that
two enzymes that contribute to the maintenance of intracellular glutathione
concentration are predictive factors for the response to cisplatin-based
chemotherapy. Since clinical cases are further complicated by interactions of the
immune system, involvement of a variety of genes related to oncogenesis, and
accompanying drugs such as 5FU, it is very difficult to determine a single factor
to predict the response to cisplatin. More precise analysis is necessary to
determine how head and neck cancer resists cisplatin.
PMID- 10191626
TI - [Prognostic significance of EGFR and p53 expression, and angiogenesis in
laryngeal squamous cell carcinoma].
AB - PURPOSE: To estimate the influence of EGFR, p53, and angiogenesis to the survival
of laryngeal cancer patients. PATIENTS: Ninety-seven laryngeal cancer patients
who received initial treatment at Gifu University Hospital from 1986 to 1996.
Patients were classified as follows: T2, 51; T3, 35; T4, 13. METHOD: Using
monoclonal antibodies against EGFR, p53, and factor VIII, respectively,
immunohistochemical staining was performed on surgically obtained biopsy
specimens. Univariate and multivariate regression analyses in accordance with Cox
proportional hazards model were performed to adjust for the possible confounding
effects and interactions of each factor. Three different end points, i.e. any
death, cancer-related death, and cancer relapse (either local recurrence or
distant metastasis), were used to evaluate overall survival, cause-specific
survival, and relapse-free survival, respectively. RESULT: In univariate
analysis, sex (P = 0.0052), age (P = 0.0038), T stage (P = 0.0096) and N stage (P
= 0.0261) were significantly correlated with overall survival; sex (P = 0.0076),
T stage (P = 0.0167) and factor VIII expression (P = 0.0443) were related to
cause-specific survival; T stage (P = 0.0005) and EGFR expression (P = 0.0103)
were related to relapse-free survival. In multivariate analysis, supraglottis (P
= 0.0296) and factor VIII expression (P = 0.0345) were significantly correlated
with overall survival; supraglottis (P = 0.0333), T stage (P = 0.0179) and factor
VIII expression (P = 0.0134) were significantly correlated with cause-specific
survival; T stage (P = 0.0166), chemotherapy (P = 0.0087) and EGFR expression (P
= 0.0016) were significantly correlated with relapse-free survival. CONCLUSION:
The present study confirmed that multivariate analysis in accordance with the Cox
proportional hazards model revealed that angiogenesis was an independent
predictor of overall survival and cause-specific survival, and that EGFR
expression was an independent predictor of relapse-free survival in patients with
T2, T3 or T4 laryngeal cancer.
PMID- 10191627
TI - [A study of cytokine in palatine tonsil--cytokine mRNA expression determined by
RT-PCR].
AB - To clarify the cytokine profile of tonsils, cytokine mRNA was determined by
reverse transcription-polymerase chain reaction (RT-PCR). The mRNA of interleukin
1 beta (IL 1 beta), IL-2, IL-4, IL-6, IL-8, interferon-gamma (IFN-gamma) and
tumor necrosis factor-alpha (TNF-alpha) were expressed on the whole tonsillar
tissue of all 5 subjects with recurrent tonsillitis, obstructive sleep apnea
syndrome caused by tonsillar hypertrophy or tonsillar focal infection. These
cytokine mRNAs were detected in tonsillar mononuclear cells freshly isolated from
all or 14 of 15 subjects. The CD4, CD8 and CD19-positive cells were purified
using immunomagnetic beads. The CD4-positive cells expressed mRNA of IL-1 beta,
IL-2, IL-4, IL-8, IFN-gamma and TNF-alpha. The CD8-positive cells expressed mRNA
of IFN-gamma and TNF-alpha. The CD19-positive cells expressed mRNA of IL-1 beta,
IL-6, IL-8 and TNF-alpha. Quantitative measurement of PCR products in tonsillar
mononuclear cells revealed that the IL-8 mRNA was expressed at a higher level
than any other cytokine. A comparison among tonsillar diseases mentioned above
revealed that the IL-1 beta and TNF-alpha mRNA were expressed at significantly
higher levels in tonsillar mononuclear cells from patients with recurrent
tonsillitis than in patients with obstructive sleep apnea syndrome caused by
tonsillar hypertrophy. These data indicate that tonsils are active immunologic
organs containing a wide variety of cytokines.
PMID- 10191628
TI - [A study of cytokine in palatine tonsil--flow cytometric analysis of cytokine
production in tonsillar mononuclear cells].
AB - Using two-color flow cytometry, we measured intracellular expression of
interleukin-1 alpha (IL-1 alpha), IL-2, IL-4, IL-6, IL-8, interferon gamma (IFN
gamma) and tumor necrosis factor-alpha (TNF-alpha) in tonsillar mononuclear cells
freshly isolated and stimulated by phorbol myristate acetate (PMA) and ionomycin.
In freshly isolated tonsillar mononuclear cells, IL-1 alpha was produced in 0.39%
of CD3 cells, 0.48% of CD4 cells, 0.66% of CD19 and 11.2% of CD14 cells; TNF
alpha was found in 5.4% of CD14 cells. After 8-hour culture without any mitogens,
IL-4, IL-8, TNF-alpha and IL-1 alpha were detected in 2.1%, 0.8%, 0.55%, and
0.42% of tonsillar mononuclear cells, respectively. Flow cytometric detection of
intracellular cytokines in tonsillar mononuclear cells stimulated with PMA and
ionomycin revealed that CD3 cells produced IL-1 alpha, IL-2, IL-4, IL-8, IFN
gamma and TNF-alpha, and CD19 cells produced IL-1 alpha, IL-6, IL-8 and TFN
alpha. In CD3 cells, the number of cells producing IL-2 and TNF-alpha were
significantly higher than those expressing other cytokines; and the number of
cells producing IFN-gamma and IL-8 were significantly higher than those
expressing IL-4 and IL-1 alpha. In CD19 cells, the number of cells producing IL-6
and TNF-alpha were significantly higher than those of IL-8 and IL-1 alpha; and
the number of cells producing IL-8 was significantly higher than that of IL-1
alpha. There was no difference in the number of CD3 and CD19 cells producing any
cytokine between the adult recurrent tonsillitis group and adult obstructive
sleep apnea syndrome group. However, the number of CD3 cells producing IL-2 or
TNF-alpha and CD19 cells producing IL-1 alpha, IL-6 or TNF-alpha were
significantly lower in children than that of adults (p < 0.05). These findings
indicate that the cytokine production in tonsillar mononuclear cells is
heterogenous according to the subset and activation and that flow cytometric
analysis of intracellular cytokines is a useful means to investigate the
pathophysiological role of cytokines in the tonsils.
PMID- 10191629
TI - [Gait disturbance in aging and equilibrium disorders--body sway research no. 45].
AB - Initiation of gait in relation to aging in normal adults and patients with
equilibrium disorders were examined by a large force platform to analyze trace of
the center of foot pressure while walking with eyes open. Sixty normal adults and
fifty-one patients with equilibrium disorders underwent examinations. Normal
adult subjects were divided into three groups by depending on the age; the young
age group (20-39 years), the middle age group (40-64 years), and the aged group
(over 65 years). The patients consisted of peripheral vestibular disorders and
central equilibrium disorders. Analyzed items were step length (mm), step width
(mm), cadence (steps/min), walking speed (m/min), step length/body height (step
length ratio), step width/step length, and LG/LS. The aged group showed
characteristic gait pattern: marked shortness of step length, broadness of step
width, slight decrease in cadence, slowness of walking speed and increased body
sway during walking. Instable body sway was expressed by step width/step length
and LG/LS. No statistically significant difference was obtained between the
normal young and the normal middle age groups. The patients with central
equilibrium disorders showed shortness of step length in comparison with
contemporary normal generations. Both patients with peripheral and central
disorders revealed remarkable lower walking speed. In the patients with central
disorders the walking was characterized with increase of body sway during their
walking.
PMID- 10191630
TI - [Molecular-genetic approach to congenital malformation syndromes].
AB - The causes of congenital malformation syndromes had long remained obscure,
because their biochemical bases were unknown. However, with recently developed
reverse-genetic and/or Human Genome Project-derived technology, we have been able
to approach such disorders. These new methods include positional cloning
techniques, candidate gene approach and positional candidate strategies. Among
them, positional cloning has become most reliable nowadays, and three ways are
mainly available to obtain position information of disease genes, i.e., data from
linkage analysis of disease families; comparative maps between different species;
breakpoints of disease-related de novo chromosomal translocations. I present here
some examples for each strategy: a large kindred with mesomelic dysplasia
Kantaputra type for linkage data, and its seemingly allelic bone dysplasia
associated with t (2; 8) for positional cloning that starts from a chromosomal
translocation; Waardenburg syndrome for candidate gene approach; and the p57KIP2
gene for positional candidate approach to Wiedemann-Beckwith syndrome. I finally
emphasize that a human link composed of general physicians, molecular geneticists
and clinical researchers is essential to reach a goal of reverse genetics.
Without such a goal, we can neither understand the genesis of diseases nor
develop their therapy.
PMID- 10191631
TI - [Brain science in the 21st century].
AB - Neuroscience has advanced markedly through the 20th century; material processes
of brains have been analyzed in detail, and information processes approached as
well. Clarification of the material processes has brought about three major
strategies to cure and prevent neurological and psychiatric diseases: creation of
new drugs, regeneration and transplantation therapy, and gene therapy. An epoch
making progress in medicine is expected to arise from the combination of these
three strategies. A trend expected in the 21st century is developmental
neuroscience on the growth and differentiation of brains. Cognitive and
computational neuroscience will also aim at the clarification of information
processes of brains. Neuroscience will exert great influence on pediatrics, in
particular on the studies of mental development in childhood.
PMID- 10191632
TI - [Child neurology and neuronal apoptosis: introductory remarks].
AB - Apoptosis is one type of cell death characterized morphologically by nuclear
condensation and shrinkage of cell bodies. Thus, it is completely different from
necrosis in features. Recently, it is suggested that apoptosis occurs in some
neurodegenerative diseases of childhood as well as adulthood. Therefore, it is
very important to reveal mechanisms of neuronal apoptosis. To the end, it is
expected that new therapies will be developed to prevent the progress of
neurodegenerative diseases. Based on such expectation, this symposium was
organized to present recent progress in neuronal apoptosis research.
PMID- 10191633
TI - [Molecular mechanism of apoptosis].
AB - Apoptosis is a cell death process morphologically distinct from necrosis. Cells
undergoing apoptosis shrink, the plasma membrane forms blebs, and the nucleus
condenses. The nuclear DNA is degraded into oligonucleosomal fragments. Apoptosis
plays regulatory and protective roles by eliminating unnecessary and dangerous
cells, respectively. Many factors involved in apoptosis have been identified,
their roles and interactions being understood at the molecular level. The bcl-2
family regulates apoptosis, and its members are classified into two groups: anti
apoptotic that inhibits apoptosis and pro-apoptotic that induces or accelerates
it. The members form dimers to inactivate each other. Caspases cleave other
members of the caspase family to activate their proteolytic activity in a cascade
like fashion, and the final target proteins prosecute apoptosis. In the case of
Fas or tumor necrosis factor receptors, apoptotic signals are transmitted to the
caspases via protein-protein interactions, whereas in other cases they originate
from mitochondria. In the early process of apoptosis, cytochrome c, which usually
is involved in the respiratory chain, is released from mitochondria into the
cytosol, then bind to Apaf-1, a homologue of CED-4 of nematoda, to process pro
caspase-9. The resulting activated caspase-9 cleaves pro-caspase-3 into an
activated form, which is responsible for the later process of apoptosis.
PMID- 10191635
TI - [Brain malformation and apoptosis].
AB - Apoptosis is a physiological phenomenon that occurs extensively in the developing
central nervous system (CNS). The death of neural cells is strictly controlled by
the bcl-2 family and other regulatory systems. In particular, neurons are
prevented from undergoing apoptosis by multiple mechanisms such as their
intracellular control device and neurotrophic factors delivered by their
innervating neurons, target cells and surrounding glial cells. A defect in any of
these may cause a CNS malformation due to massive neuronal death.
PMID- 10191634
TI - [Apoptosis and neurotrophic factors].
AB - Neurotrophic factors are endogenous soluble proteins regulating development,
differentiation, and survival of neurons. They are secreted from target cells or
surrounding glial cells and act on the neurons via their receptors on the cell
membranes. Several factors are reported to promote survival of motor neurons in
vitro and to rescue developing motor neurons from naturally occurring cell death.
Administration of the factors has also been shown to rescue motor neurons from
degeneration after axotomy in adult as well as neonatal rodents. On the basis of
these lines of evidence, neurotrophic factors have been considered to be
potential candidates for drugs alleviating human motor neuron diseases such as
amyotrophic lateral sclerosis (ALS). Although some factors such as ciliary
neurotrophic factor and brain-derived neurotrophic factor slowed down the disease
progression in animal models of motor neuron disease, phase III clinical trials
showed no therapeutic effects for ALS patients treated with these factors. There
may be some reasons for this lack of success in humans. Several important issues
remain to be resolved such as the drug delivery systems for neurotrophic factors
and combination of neurotrophic factors with complementary effects.
PMID- 10191637
TI - [Apoptotic cell death in child-onset neurodegenerative disorders].
AB - Apoptotic cell death was examined in autopsied brains with Werdnig Hoffmann
disease, hereditary DNA repair disorders (xeroderma pigmentosum and Cockayne
syndrome) and neuronal ceroid lipofuscinosis, using in situ nick end labeling
(TUNEL) and immunohistochemistry for cell death-related proteins. TUNEL-positive
cells were found in the thalamus, cerebellum and/or hippocampus in each disorder.
The expression of cell death-related proteins in the cerebellum of hereditary DNA
repair disorders and the hippocampus of neuronal ceroid-lipofuscinosis suggested
the involvement of apoptotic process in neurodegeneration in these disorders. On
the other hand, TUNEL-reactivity without the altered expression of cell death
related proteins might reflect neuronal changes preceding the thalamic
degeneration in Werdnig-Hoffmann disease.
PMID- 10191636
TI - [Perinatal ischemic brain damages and apoptosis].
AB - Perinatal brain damages are caused mainly by circulation insufficiency due to
intrauterine or birth asphyxia. Hypoxic-ischemic encephalopathy (HIE) and
pontosubicular neuronal necrosis (PSN) are typical perinatal ischemic diseases.
We investigated the expression of apoptosis in these diseases, using TdT-mediated
dUTP nick end labeling (TUNEL) method and immunohistochemistry with Bcl-2, Bcl-x,
Bak and caspase 3 (CPP 32). In HIE, Purkinje cells showed overexpression of Bcl-2
and CPP 32, and some karyorrhectic cells were positive for TUNEL. In PSN, neurons
of the pontine nuclei showed overexpression of Bcl-x and CPP 32, and most
karyorrhectic neurons were positive for TUNEL. Immature neurons were susceptible
to these changes. Apoptosis may play an important role in the pathomechanism of
perinatal ischemic brain damages.
PMID- 10191638
TI - [Methods of sleep induction for EEG recordings: comparison between three
hypnotics and natural sleep].
AB - We compared the effects of three oral hypnotics, monosodium trichloroethyl
phosphate (MTP), chloral hydrate (CH), and pentobarbital calcium (PTB), to those
of non-medication on wake-sleep states and sleep activation of epileptic seizure
discharges. The subjects consisted of 410 epileptics and 171 non-epileptic
outpatients (mean age: 12.5 years) of the Department of Pediatrics, Nagoya City
University Hospital. Complete EEG records including awake and sleep states were
obtained in 230/241 (95%) of patients with MTP, 20/22 (91%) of those with CH,
72/85 (85%) of those with PTB, and 225/233 (97%) of those without any hypnotics.
There were no statistically significant differences in the effect of sleep
induction among the four groups. Sleep activation effects were observed in 25% of
patients with natural sleep and 35% of those with induced sleep. There was no
statistical difference (p > 0.05). These results suggested MTP, CH, and PTB are
useful hypnotics for sleep EEG recordings.
PMID- 10191639
TI - [A case of hypertensive encephalopathy secondary to nephrotic syndrome].
AB - We reported a 15-year-old boy with hypertensive encephalopathy secondary to
nephrotic syndrome (minimal change). Based on his clinical symptoms such as
anasarca and oliguria, and laboratory data, he was diagnosed as having nephrotic
syndrome, and treated with corticosteroid. On the 6th days of admission, he
experienced multifocal seizures with hypertension. Cranial T2-weighted MR imaging
revealed multiple small cortical and subcortical high intensity lesions in the
parieto-occipital lobes, and bilateral round shaped lesions in the cerebellar
white matter. He was successfully treated with antihypertensive and
anticonvulsant drugs. One year later, a follow up MR imaging revealed almost
complete resolution of the brain lesions. MR imaging is a useful modality to
demonstrate the lesions characteristic of hypertensive encephalopathy, which are
distributed in the areas of posterior circulation.
PMID- 10191640
TI - [Ventricular outflow tract obstruction by cardiac tumors during ACTH therapy of
an infant with tuberous sclerosis].
AB - In an infant with tuberous sclerosis and West syndrome, ACTH treatment was
interrupted because of augmentation of the biventricular outflow tract
obstruction. A 5-month-old boy, who had been diagnosed to have multiple cardiac
tumors since in utero, manifested West syndrome with typical hypsarhythmia in
EEG. Several days after starting low dose ACTH treatment, a systolic murmur due
to biventricular outflow tract obstruction intensified with ventricular
arrhythmia. A tumor in the left ventricular outflow tract was enlarged.
Discontinuation of daily administration of ACTH and administration of a beta
blocking agent improved the cardiac problems. Acceleration of blood velocity in
the outflow tracts disappeared two months later. Intracardiac morphology and
hemodynamic performance should be monitored to avoid critical complications
during ACTH treatment in patients with tuberous sclerosis.
PMID- 10191641
TI - [Connatal type of Pelizaeus-Merzbacher disease: a case report].
AB - Pelizaeus-Merzbacher disease (PMD) is a hereditary disorder with myelin dysplasia
in the central nervous system. The connatal type is a more severe form compared
to the classical type and shows developmental arrest or deterioration, nystagmus,
spasticity, and/or convulsions in the neonatal period. A 1 1/4-year-old Japanese
boy diagnosed as connatal type PMD is reported here. Soon after his birth, he
demonstrated horizontal and rotatory nystagmus and opisthotonic posture. At the
age of 10 months, he had difficulty in feeding. At the age of 1 year, he
presented more severe opisthotonic posture and frequent vomiting. He showed
deterioration in gross motor development. His chromosome analysis showed a normal
male karyotype. Electroencephalogram did not show a sleep spindle. Auditory
evoked brainstem responses (ABR) showed only wave I on both sides. Visual evoked
potentials (VEP) showed prolongation of latencies. These results were compatible
with PMD. Nuclear magnetic resonance imaging (MRI) demonstrated in the white
matter of cerebrum and brainstem no high intensities on T1-weighted images and
diffuse high intensities on T2-weighted images. Such absence of myelination
including the brainstem was characteristic to the connatal type PMD. The diffuse
disturbance of myelination appeared to correlate with the severity of clinical
symptoms.
PMID- 10191642
TI - John Snow revisited: getting a handle on the Broad Street pump.
PMID- 10191643
TI - Creating the future: rather than simply reacting to it.
PMID- 10191644
TI - From transplant clinic.
PMID- 10191645
TI - Around the continent in 180 days: the controversial journey of Abraham Flexner.
PMID- 10191646
TI - Motivation for medical education reform: the post-Flexner era.
PMID- 10191647
TI - Commentary on Flexner's impact--then and now. A profound effect on medical
education, research, practice.
PMID- 10191648
TI - Today's emergence of a new post-Flexnerian medical model.
PMID- 10191649
TI - Making meaning of illness: Arthur Frank's The Wounded Storyteller.
PMID- 10191650
TI - Our academic medical centers: let us modify them now, not later.
PMID- 10191651
TI - From managed care to managed neglect?
PMID- 10191652
TI - Organ donation and fire insurance--an analogy?
PMID- 10191653
TI - Female infertility: radiology and endoscopy in morphofunctional imaging.
PMID- 10191654
TI - Evolution of radiologic procedures in the study of female infertility.
PMID- 10191655
TI - Endoscopy in gynecology.
PMID- 10191656
TI - Normal uterus and uterine malformations.
AB - The uterus is well visualized with sonography with the definition of its
morphofunctional characteristics and the physiologic variations in relation to
hormonal stimuli. With high frequency endovaginal and intrarectal probes,
anatomical details are optimal. Color Doppler enables the study of blood flow in
the pelvic vessels and supplies functional information. Hysterosalpingography is
the most accurate method for the study of the uterine cavity and the evaluation
of tubal patency. In the study of uterine malformations, sonography represents
the procedure of first choice, able to diagnose anomalies of fusion and
development of mullerian ducts. In cases of dubious or ascertained malformations,
hysterosalpingography is mandatory to complete the sonographic findings.
PMID- 10191657
TI - Endoscopy of the uterus and its congenital malformations.
AB - Laparoscopy and hysteroscopy are two endoscopic procedures with which the outer
surface of the uterus, its cavity can be studied with a detailed analysis of the
endometrium and ostia. The stages of the study are described and uterine
congenital malformations are described in relation to the reproductive
performance of women.
PMID- 10191658
TI - Uterine intracavitary disorders: role of sonography and combination with other
radiologic techniques.
AB - Since it serves as the site for the implantation of the fertilized ovum, it is
evident that significant disorders in the uterine cavity and endometrial mucosa
represent potential factors of sterility/infertility. Among the acquired
pathological conditions, a possible cause of sterility, there are inflammatory
(endometritis) or post-traumatic (synechiae) disorders and proliferative mucosal
(endometrial hyperplasia, polyps) and muscular (fibroma) disorders. Sonography
(by transabdominal or preferably endovaginal route, and sonohysterography) is the
first choice procedure being in most cases adequate for clinical assessment.
According to the specific disease, the diagnostic combination with hysteroscopy,
hysterosalpingography, Magnetic Resonance Imaging can be suitable.
PMID- 10191659
TI - Diagnostic imaging in cervical incompetence.
AB - Cervical incompetence is defined as an abnormal dilatation of the cervical canal
at the body-neck junction with no pain or blood loss and in the absence of
uterine contractile activity. Cervical incompetence is the frequent cause of
abortion in the second trimester and premature delivery, with adverse fetal
prognosis. Usually, three causative factors are considered: traumatic,
constitutional, dysfunctional. While in multiparous women the medical and remote
obstetric history poses the diagnostic suspicion, in primigravidae, in the
absence of previous risk factors (traumas, malformations, etc) early diagnosis
may allow prompt treatment with a better prognosis. Hysterosalpingographic
(tunnel-shaped cervix or appearing as an inverted sac, diameter of internal
uterine orifice) but especially sonographic findings (cervical length, dilated
endocervical canal, tunnel-shaped internal uterine orifice, herniation of the
amniotic sac into the endocervical canal) represent the most significant
radiologic signs. The radiologist should be able to recognize the typical imaging
of this condition to select the patients who should undergo serial controls in
time since the start of the second trimester of pregnancy, or to indicate a
suitable treatment based on sonographic signs suggestive for incompetence
identified before the clinical exam. This is the present correct approach while
waiting for future clinical and technological developments of three-dimensional
sonography and MRI which will be able to detect those changes in cervical
connective structures responsible for incompetence and still not identified by
any imaging procedure.
PMID- 10191660
TI - Conventional ultrasonography and color Doppler velocimetry of uterine leiomyomas.
AB - The role of uterine leiomyomas as causative factor of sterility is controversial.
Submucosal myomas, in particular, can interfere with fertility and be associated
to obstetric complications as abruption of placenta, post-partum metrorrhagia and
puerperal sepsis. With ultrasonography, immediate and long-term information can
be drawn on changes in the features of myomas. However, to-date, there are no
reliable noninvasive exams to assess the nature and growth pattern of myomas.
With Doppler velocimetry in ovarian malignancies a vascularization significantly
different from that observed in benign tumors, is detected. It has been
hypothesized that within benign tumors, as myomatous masses, tissues with
different cell proliferation rates could be characterized by different vascular
patterns. In a group of myomas shown to have central arterial vessels at Doppler
examination, significant correlations were assessed between resistance indices of
analyzed vessels and percentage of cell in the proliferative phase evaluated with
cytofluorimetry. The myomatous tissue with high cell proliferation rate seems to
have higher vascular resistances.
PMID- 10191661
TI - Hysteroscopic diagnosis of uterine intracavitary disorders.
AB - The fundamental role of hysteroscopy in the diagnosis of intracavitary disorders
in gynecology and in particular in female sterility and infertility, is stressed.
The outcomes of a 12-year experience with hysteroscopy, are reported. Its
indications, contraindications and side-effects in a group of 7327 patients
undergoing hysteroscopy, are discussed. In this patient population, sterility and
infertility were the second most common indication for hysteroscopy after
abnormal uterine bleeding. The role of malformations such as uterus septus and
subseptus, inflammation with hysteroscopic findings of uterine synechiae and
focal lesions as polyps and myomas was examined. Particular attention was paid to
the study of tubal ostia and endometrial morphology in relation to the phase of
menstrual cycle. In a smaller group of infertile patients, hysteroscopy was
compared with hysterosalpingography, stressing the sensitivity and specificity of
the latter as compared to the former.
PMID- 10191662
TI - Radiologic imaging of the fallopian tubes.
AB - Aim of the present article is to illustrate the radiologic findings which afford
the most reliable diagnosis with hysterosalpingography, in the evaluation of
tubes in infertile patients. Based on the more regular anatomical patterns with
details of minor anatomical variants, a common cause of infertility, the signs of
the various types of tubal obstruction, are examined. The nature of the latter is
not always organic: the implementation of simple albeit often resolutive
technical devices as change of position or the use of more sophisticated but well
tolerated maneuvers as the interventional ones, may help detect normal patterns
hidden by false (functional) obstruction. Careful analysis of tubal morphology
down to the obstructed portion allows the identification of true pathologic
patterns, making this exam even more valid in the diagnostic approach to the
infertile patient.
PMID- 10191663
TI - Tubal factor infertility.
AB - Various studies demonstrated that there is no close correlation between the
intratubal damage and the extent and type of pelvic adhesions. Moreover, the
results of prospective studies on the prognostic value of salpingoscopy showed
that the tubal mucosal status is the most important prognostic factor in terms of
reproductive outcome. Salpingoscopy has modified the management of patients with
tubal infertility, since the accurate evaluation of the tubal mucosa permits the
selection of patients with a normal mucosa (34-42% of the patients with
hydrosalpinx and 76-80% of those with periadnexal adhesions) who can benefit from
tubal reconstructive surgery. In these patients the term pregnancy rate is 60% in
case of hydrosalpinx and 70% in case of periadnexal adhesions.
PMID- 10191664
TI - Endometriosis externa and interna: endoscopic diagnosis.
AB - Endometriosis is defined as the presence of the endometrium outside the
endometrial cavity. If the ectopic mucosa is located within the endometrium, the
disease is defined as endometriosis interna, or adenomyosis, whereas the
localization of the endometrium outside the uterus is defined as endometriosis
externa, or pelvic endometriosis. The diagnosis of pelvic endometriosis requires
invasive techniques, such as laparoscopy or laparotomy, with histologic
confirmation on the surgical specimen. The diagnosis of adenomyosis should be
based on histology of hysterectomy specimen, since the endoscopic diagnosis is
still too inaccurate. Laparoscopy allows the visualization of the different
aspects of pelvic endometriosis, i.e. superficial implants, deep lesions, and
associated adhesions. Staging is based on a score attributed to each location in
order to establish a prognosis in terms of the patient's reproductive
performance.
PMID- 10191665
TI - Uterine adenomyosis and tubal endometriosis: diagnostic imaging.
AB - Endovaginal sonography plays a major role in the study of pelvic endometriosis
and uterine adenomyosis. Other procedures as CT or MRI are reserved for
particular cases. Diagnostic problems and main radiologic findings are analyzed.
PMID- 10191666
TI - Magnetic resonance imaging of pelvic endometriosis.
AB - Endometriosis is a multifocal disease involving multiple pelvic sites. Although
laparoscopy is the elective exam in the study of patients with clinically
suspected endometriosis, MR imaging represents a valid noninvasive procedure for
the study of areas unapproachable with laparoscopy. On MR imaging, areas of
endometriosis over 1 cm in size appear homogeneously hyperintense in T1-weighted
images and hypointense in T2-weighted images, while areas of endometriosis less
than 1 cm in size appear hyperintense in T1-weighted images and with variable
signal in T2-weighted images. Endometriosis may also appear as small cystic
lesions, hyperintense in T1-weighted images. While MR imaging has some
limitations in the visualization of small endometriotic implants and adhesions,
it has the ability to characterize the lesions, to study extraperitoneal
locations and the contents of pelvic masses. The reliability of MR imaging
findings of endometriosis and the assessment of pelvic organ involvement is
important for guiding subsequent laparoscopy.
PMID- 10191667
TI - Ovarian factor infertility.
AB - The diseases of the ovary which most frequently cause infertility are:
anovulation from follicular atresia, the empty follicle syndrome, the luteinized
unruptured follicle syndrome; chronic anovulation syndromes, within which
polycystic ovarian syndrome plays a major role; ovarian endometriosis. Sonography
and Color Doppler US are the first choice procedures in the monitoring of ovarian
cycles, which combined with serum hormone values, are able to identify possible
changes in the physiologic sequence of the cycle. In follicular atresia, ovaries
with minute follicles (3mm or less) and early disappearance of primary follicle
are observed on sonography. The empty follicle syndrome characterized by the lack
of oocytes within the primary follicle, is of difficult sonographic diagnosis, a
possible sign being the missed visualization of cumulus oophorus. The luteinized
unruptured follicle syndrome consists in the absence of oocyte expulsion from
primary follicle persisting more than 48 hours after LH blood peak. Doppler
spectra of blood flow in perifollicular ovarian arteries maintain the features of
the follicular phase, i.e. low diastolic velocities and high resistances. Among
chronic anovulation syndromes, hyper-and hypogonadotropism cause ovarian
amenorrhea where ovaries are similar to those of women in menopause: small size,
very few or absent follicles. The polycystic ovarian syndrome is characterized by
an abnormal pulsatile GnRH release which causes LH hypersecretion and FSH
hyposecretion. The latter is not able to stimulate the growth and maturation of
follicles, while the former causes hyperandrogenism with hirsutism and obesity
and is responsible for hypertrophy and stromal hyperechogenicity. The sonographic
diagnosis of polycystic ovarian syndrome is based on standardized
morphostructural signs as increased volume of the ovaries (> 10 cm3), the
presence of numerous (> or = 10) peripheral microfollicles (< or = 5 mm) with
hyperechoic stroma. The endometrial cyst, usually present in ovarian
endometriosis is visualized with sonography as a round neoformation with ill
defined walls, filled with a uniformly hypoechoic, corpuscular, partly
hemorrhagic fluid; less frequently the appearance is that of a more complex
structure posing differential diagnostic problems, mainly with the hemorrhagic
corpus luteum; both pathological conditions appear poorly vascularized at Color
Doppler, with tracings of high resistance arterial flow. Among the procedures of
second choice, CT can show the high blood density common to the two conditions
while on MRI the signal is mostly hyperintense in T1-weighted sequences with
areas of lower signal intensity in T2-weighted sequences.
PMID- 10191668
TI - Endoscopy of ovarian factor sterility.
AB - After an overview of normal ovarian morphology assessed during diagnostic
laparoscopy, the typical patterns most frequently associated to ovarian factor
sterility, observed in gonadal dysgenesis and dysfunction syndromes as LUF or
follicular cysts, polycystic ovary, postinflammatory adhesions and endometriosis,
are analyzed. Laparoscopic surgical procedures as ovarian biopsy and lysis of
adhesions are briefly mentioned.
PMID- 10191670
TI - Operative laparoscopy.
AB - Operative laparoscopy has replaced the conventional approach by laparotomy to the
treatment of most benign gynecological diseases (benign adnexal cysts, ectopic
pregnancy, tubal infertility, polycystic ovarian disease, endometriosis, myomas),
with advantages in terms of shorter hospital stay, less discomfort and
complications for the patient, minor social costs due to the early resumption of
normal working activities, and comparable results in terms of reproductive
outcome.
PMID- 10191669
TI - Tubal catheterization and selective salpingography.
AB - Hysterosalpingography with selective salpingography is by now a well-established
technique in the diagnosis and therapy of some forms of female sterility
especially in relation to tubal disease. The experience with a group of 302
patients with unilateral (187) or bilateral (115) proximal tubal disease, is
reported. As for the catheterization of obstructed tubes, the technique was
successful in about 94% of cases, while failure was observed in 6% of cases due
to organic disease which hindered the transit of the angiographic guidewire or
catheter. 10% of all the patients achieved spontaneous pregnancy while artificial
insemination was performed in 15%. A 12-month follow-up of 10 women undergoing
hysterosalpingography showed in approximately 60% of cases a new uni-or bilateral
proximal tubal obstruction. No immediate or late severe procedure-associated
complications were observed. Extrauterine pregnancy occurred in 2% of cases,
probably due to the restored patency in tubes lacking physiologic motility.
PMID- 10191671
TI - Morphologic aspects of balloon angioplasty and related procedures.
PMID- 10191672
TI - Coronary angioplasty in Portugal.
AB - Coronary angioplasty began in Portugal in 1984 at the Santa Cruz Hospital and has
developed progressively, being practiced in twelve hospitals since 1997. The
number of patients with ischemic cardiopathy per annum that are submitted to this
form of therapy has also increased. The increase is mainly in the past five
years, from 684 procedures in 1993 to 3,005 in 1997. With regard to new devices,
the use of intracoronary stents, which began in 1990 in Portugal is currently
practised in all hospitals, 2,364 stents were implanted in 1997. This development
of angioplasty has made it definitively established in Portugal, even in
hospitals without cardiac surgery, as an alternative treatment to coronary
surgery and medical treatment. In the absence of a national registry of
interventional cardiology, which allows data to be gathered on the type of
patients and the clinical situations in which angioplasty is used, it is not
possible to ascertain whether medical treatment or surgical treatment have gained
patients. Without evidence that surgery has decreased, it is presupposed that the
increase in angioplasty is mainly the result of a greater number of diagnostic
coronariographies. The current continued growth which has been observed, gives
the impression that the development of the early diagnostic suspicion of coronary
disease, easier access to coronariographies even in district hospitals and the
improvement of technical conditions and manpower in central hospitals will
sustain the increase in angioplasty in coming years. In becoming the solution to
the problem of restenosis, angioplasty may undisputedly become the most promising
therapeutic alternative in ischemic cardiopathy, in parallel with
hypercholesterolemia control and other coronary risk factors.
PMID- 10191673
TI - Coronary angioplasty in Brazil.
AB - In 1979, the first transluminal coronary angioplasty (PTCA) was performed in
Brazil, two years after the original contribution of Andreas Gruentzig, in
Zurich. In the years which followed, the development of PTCA in the country grew
and in the mid eighties several centres had already had the experience of more
than 600 cases. In the beginning of the nineties, PTCA underwent an additional
promotion with a large number of procedures, now subventioned by the bodies of
public health. In addition to this, the introduction of new technologies such as
directional atherectomy, rotablator, laser and stents. In 1991, the Brazilian
Society of Interventional Cardiology created a national registry (CENIC) to
gather data on the coronary procedures performed in the country. The CENIC data
for the 1992/1993 and 1996/1997 bienniums were compared and it was observed that
there had been a significant increase in the number of cases treated (from 16,429
in 92/93 to 22,025 in 96/97), complex lesions of the B/C type (from 71.4% to
92.3%), patients with previous revascularisation (from 22% to 28.3%), acute
myocardial infarction (from 16% to 17.4%) and multiarterial lesions (from 34.4%
to 38.8%). However, despite a greater clinical and angiographic complexity, the
success of the procedure grew (from 89.7% to 92.8%) and complications reduced:
acute occlusion (from 3.2% to 1.5%); acute myocardial infarction (from 2.5% to
1.2%) and death (from 1.8% to 1.4%). Interventional cardiology in Brazil has
consequently progressed at the same rate as that of other countries. The
incorporation of new technologies, particularly coronary endoprostheses has
increased, guaranteeing better success rates, better results and a decrease in
complications arising from acute occlusion of the target vessel.
PMID- 10191674
TI - Coronary angioplasty in the United States.
AB - Coronary angioplasty has evolved in the twenty years since its introduction to
become the procedure of choice for a wide variety of coronary lesions and
ischemic presentations. Optimal results require highly trained cardiologists who
perform procedures frequently, high volume centers with well trained staff,
proper selection of patients and lesions, availability of adjunctive devices such
as atherectomy and stents, appropriate use of available pharmacologic agents,
appropriate use of alternative therapies such as bypass surgery and medical
therapy, and close working relationships with surgical teams. With such an
approach, procedural success rates should be greater than 90%, emergency bypass
rates around 1%, and mortality well under 1%. As equipment, technique, and
understanding of the endovascular environment improve, angioplasty will continue
to be an important part of the overall treatment of patients with coronary artery
disease.
PMID- 10191675
TI - The role of platelet glycoprotein IIb/IIIa antagonists in percutaneous coronary
revascularization procedures.
AB - Platelet activation occupies a central role in arterial thrombosis after vascular
injury, and the platelet glycoprotein GPIIb/IIIa integrin mediates the final
common pathway for platelet aggregation. Agents of the recently developed
pharmacologic class of inhibitors of the platelet GPIIb/IIIa receptor have been
shown to decrease ischemic complications after coronary revascularization
procedures. However, several issues need to be determined with respect to their
specific indications, dosage, and combination with other antithrombotic
therapies. Intracoronary thrombus formation during percutaneous coronary
interventions (PCI) is the main pathogenic mechanism of the acute complications
of PCI, but has also been implicated in the pathogenesis of their long-term
results. In order to target intracoronary thrombosis, all PCIs have been
performed during intense short-term anticoagulation with combination of
unfractionated heparin plus aspirin. Compelling data on the central role of
platelets in arterial thrombosis have made apparent the need for more potent
antiplatelet agents for the treatment of patients undergoing PCI.
PMID- 10191676
TI - Coronary angioplasty in chronic total occlusion.
PMID- 10191677
TI - Coronary intervention in acute myocardial infarction.
PMID- 10191678
TI - Coronary angioplasty in cardiogenic shock.
PMID- 10191679
TI - Coronary stenting: "current state of the art".
PMID- 10191680
TI - The ideal characteristics of a coronary stent.
PMID- 10191681
TI - The value of intravascular ultrasound in interventional cardiology.
AB - Intracoronary ultrasound (ICUS) is a new imaging technique with the unique
ability to study vessel wall morphology in vivo, accurately displaying the
details of vessel structure. The coronary angiogram represents only a
projectional image of the vessel lumen without providing any information
concerning vascular wall architecture. Interventional cardiology has developed
over the last years with the appearance of new devices and consequently new
challenges. The selection of an appropriate device and the assessment of any
intervention, as well as the understanding of its mechanisms is essential to
perform a better intervention. The use of a tool, such as ICUS, able to identify
vessel wall anomalies, complementing coronary angiography, seems to be an
appropriate method in the regard. The last years have witnessed an array of
studies demonstrating the advantages and disadvantages of ICUS in the setting of
interventional cardiology. Despite some contradictions in the literature, the
result of a new technology still under scrutiny, it is possible to summarise some
of the major achievements: Lesion assessment before coronary interventions for
selection of treatment, including calcium detection, plaque eccentricity, diffuse
atherosclerotic disease, type of vessel remodelling; ICUS during balloon
angioplasty has helped in balloon diameter selection, identification of pseudo
successful results and presence/severity of wall dissections, as well as the
search of predictors of restenosis; during rotational and directional
atherectomy, ICUS can help in the definition of the lesion most suitable for
rotational atherectomy, showing if there is a diffuse sub endothelial
calcification, excluding unsuitable lesions, selecting cut direction and directly
assessing the adequacy of plaque removal; during stent implantation it helps to
determine if there was a complete apposition, detect residual narrowing or
proximal/distal stenoses or dissections requiring further treatment. Some new
concepts have been introduced by ICUS, such as the negative remodelling as one of
the mechanisms of restenosis. New developments are under way, including combined
devices, looking forward ultrasound, high frequency probes, imaging wires, tissue
characterisation and three dimensional technology. Therefore, ICUS has reached
enough maturity to be considered an important tool in the catheterization
laboratory, complementing the information provided by coronary angiography.
However, some more research needs to be done to answer some important questions
regarding the whole array of potential applications in an environment of cost
containment as the one we live in today.
PMID- 10191682
TI - Coronary angioplasty and new devices in patients with prior coronary artery
bypass graft surgery.
PMID- 10191683
TI - [Bj"ork-Shiley heart vales at the Bern University Hospital. Long-term follow-up
of 12 to 23 years after mitral and aortic valve replacement in 503 patients].
AB - Long-term follow-up, cardial complications and factors influencing the survival
time have been investigated retrospectively in 503 patients, who underwent 344
aortic and 191 mitral valve replacements with Bjork-Shiley heart valve prosthesis
between 1973 and 1984 at the University Hospital of Berne, Switzerland.
Informations were assessed from the patient's files and a questionnaire to the
family physician. The cumulative follow-up contains a total of 4,810 patient
years or a median of 14 years per patient. The median survival time was 19 years,
hardly less than the normal life expectancy. Of the 135 patients found alive in
1996 66% had no cardiac problems at all. Two cases of outlet strut fracture of
the Bjork-Shiley valve were reported during the follow-up time. Both patients had
a mitral valve replacement in 1982 with a 31 mm Bjork-Shiley valve because of
mitral stenosis. The most common complication was a thromboembolic incident (1.6
in 100 patient years). Furthermore eight cases of valve thrombosis, 16 of
endocarditis and 24 of myocardial infarction occurred in this population. The
study showed that survival time after heart valve replacement with Bjork-Shiley
valve is long. The mortality was elevated significantly with the following
preoperative findings: severe dyspnea (x 2.0), pulmonary congestion (x 1.7) and
increased cardiac size (x 1.5). The survival time was shorter when a valve
prosthesis with a diameter larger than 27 was used or when in addition coronary
heart disease, hypertension, diabetes mellitus or obesity were present.
PMID- 10191684
TI - [Controversy regarding the sequelae of minor craniocervical trauma with special
reference to neurobiological aspects of cognitive disorders].
AB - This paper focuses primarily on the biomechanical factors which may lead to a
substantial brain-tissue lesion following cranio-cervical trauma. Emphasis is
placed on pathoanatomical findings and clinical parameters in the assessment of
trauma-severity. Results from previous research are highlighted to demonstrate
close interrelationship between the severity of a trauma and neurological,
psychological, neuropsychological sequelae or lesions visible by neuroimaging.
Knowledge of this interrelationship clearly indicates the necessity of proper
initial assessment to allow reliable prognosis of outcome and establishment of
treatment strategies.
PMID- 10191685
TI - [Achieving self-destruction of cancer cells].
PMID- 10191686
TI - [Hemoperitoneum--how to proceed?].
AB - This case report presents a patient with liver cirrhosis and hematoperitoneum. In
about 5-15% of all patients with liver cirrhosis and ascites a hematoperitoneum
is present. In most cases such intraperitoneal bleedings are asymptomatic and
will be diagnosed only by diagnostic paracentesis of the ascites. Aside from
rupture of intrahepatic tumors as origin of hemorrhagia or spontaneous bleeding
out of varices other possible causes are discussed such as carcinomatosis of the
peritoneum, spontaneous bacterial peritonitis and perforation of vessels due to
diagnostic puncture. For a correct and complete diagnostic work-up it is
important to gain as much ascites as possible and perform all relevant analyses
including biochemical, cytological and hematological ones on the ascites. The
incidence of iatrogenic bleeding due to punction of ascites and the therapeutic
consequences of hematoperitoneum are discussed.
PMID- 10191687
TI - [Angioneurotic edema].
PMID- 10191688
TI - [Thoracic pain and multi-drug abuse].
PMID- 10191689
TI - [The status of crime in Russia and the tasks in improving the efficacy of
utilizing forensic medical potentials in investigatory practice].
PMID- 10191690
TI - [The morphological characteristics of chronic subdural hematomas].
AB - Preparations of chronic subdural hematomas (CSH) obtained during surgery from 29
patients aged 19-50 years are studied. Histological sections were stained with
hematoxylin-eosin after van Gieson. Morphological criteria of CSH variants are
defined, permitting forensic medical experts to make well-based conclusions on
the nature (traumatic or not) of CSH (two types of capsules) and the time when it
occurred.
PMID- 10191691
TI - [The forensic medical assessment of the micromorphology of brain stem hemorrhages
in craniocerebral trauma].
AB - Microscopic features of primary and secondary hemorrhages in the stem portion of
the brain in craniocerebral injuries are described. Criteria of differential
diagnosis between primary and secondary hemorrhages in the stem in subjects dead
during 24 h after isolated and combined craniocerebral injuries are defined. The
forensic medical significance of differential diagnosis of hemorrhages in the
stem for the solution of many expert problems is evaluated.
PMID- 10191692
TI - [The expert assessment of the force of blows by blunt solid objects].
AB - The author distinguishes 4 degrees of strength of strikes inflicted with blunt
hard objects. Intervals of strength expressed in newtons correspond to each of
these degrees. The scheme is based on experimental data of many authors who
determined the parameters of strength of strikes inducing certain injuries. Use
of the proposed scheme will render objectiveness and reliability to conclusions
of forensic medical experts.
PMID- 10191693
TI - [Establishing the cause of death in finding a corpse on a flight of stairs].
AB - A total of 793 forensic medical conclusions concerning corpses found in
vestibules are analyzed. The circumstances of death were unknown in the majority
of cases. Causes other than injuries were responsible for the majority (72.4%) of
deaths: coronary diseases, hanging, alcohol intoxication, or general hypothermia.
Strikes with blunt objects and falling on the staircase or floor rank second
among causes of death. Injuries caused by falling from staircase and cases with
this cause suspected were responsible for 9.6% deaths. Murders with acute objects
and guns were recorded in 6% cases. For facilitating differential diagnosis, a
list of signs and injuries occurring as a result of falling from staircase and
main causes of death in such injuries, made with consideration for the place
where the corpses are found, is offered.
PMID- 10191694
TI - [The advantages of establishing the species classification of blood and other
biological objects by the IFR in a quantitative modification].
AB - A quantitative modification of immunofluorescent test (IFT) is described. It was
used for species identification of blood stains on material evidence objects.
This modification is 1000 times more sensitive than electrophoretic methods
traditionally used for this purpose in forensic medicine. Computer processing of
the results helps objectively and persuasively determine the species appurtenance
of blood and other biological objects. Results of the test represented as
histograms should be attached to forensic medical conclusions as proofs for the
court.
PMID- 10191695
TI - [The capacity of the victim for active functioning with a fatal gunshot wound to
the brain].
PMID- 10191696
TI - [The teaching of a course on the "Legal bases of a physician's activities" in
forensic medicine departments].
PMID- 10191697
TI - [The autopsy on the body of A. S. Pushkin].
PMID- 10191698
TI - [Regulations on the production of forensic medical expertise on matters in
criminal and civil cases. Appendix 8 to the order of the Ministry of Public
Health of the Russian Federation of 10 December 1996 No. 407. Coordinated with
the General Public Prosecutor, the Supreme Court and the Ministry of Internal
Affairs of the Russian Federation].
PMID- 10191699
TI - [Differentiated local therapy of chronic wounds with modern wound dressings].
AB - Differentiated local therapy of chronic wounds with modern wound dressings. The
therapy of chronic wounds comprises besides treating the underlying disease, for
instance compression therapy and phlebosurgery with venous ulcus cruris modern
differentiated local therapy. Conventional wound therapy comprises primarily of
colour solutions, various ointments, local antimicrobial agents, and sterile
pressure bandages. Although it has been proven that conventional methods impede
wound healing compared with modern wound dressings they are still widely used. In
comparison the principle of moist wound healing is the basis of modern
differentiated wound therapy. Therefore a vast number of modern wound dressings
has been established in the last years. As not every wound dressing is suitable
for every type of wound the knowledge of available modern wound dressings is
essential in order to choose the wound dressing which is most suitable for the
individual case. In the exudation/cleaning phase polyurethane foams, alginates
and dressings containing activated charcoal are indicated. They can also be used
in the granulation phase. The granulation phase is main indication for
hydrokolloids and hydrogels. They are also used beside non-adhesive dressings and
alginates in the epithelialisation phase. Besides the above synthetic wound
dressings cytokines and biological skin equivalents are increasingly used in
modern wound therapy. Biological skin equivalents comprise of epidermis
equivalents, dermis substitutes and combined epidermis-dermis equivalents which
are being developed at present. These will possibly be more effective on wound
closure. Phase adapted use of modern wound dressings enables acute and chronic
wounds to heal quickly and without complications. Present clinical studies are
evaluating the importance of cytokines and new vital skin substitutes, which
might offer interesting possibilities for further improvement in wound treatment.
PMID- 10191700
TI - Comparison of haemostatic parameters in arterial and venous blood from patients
with peripheral arterial occlusive disease.
AB - BACKGROUND: Several studies proved the co-existence of peripheral arterial
occlusive disease (PAOD) and hypercoagulability. However, in practice coagulation
parameters are mainly determined from venous blood samples. In this study several
coagulation parameters in arterial and venous blood were examined for differences
and the validity of coagulation parameters determined in venous blood was
investigated. PATIENTS AND METHODS: In 22 patients with peripheral artery disease
venous and arterial blood samples from vessels of the diseased leg were examined
for the concentration of thrombine-antithrombine III-complex (TAT), prothrombin
fragments (F1 and F2) and D-dimers, and results were compared. RESULTS: Mean
concentrations of TATs and prothrombin fragments F1 and F2 were significantly
higher in arterial than in venous blood. TAT-complex was the most sensitive
parameter for quantification of thrombin generation. D-dimer levels did not
differ in arterial and venous blood. TAT and F1 and F2 concentrations in arterial
and venous blood did not correlate in individual patients whereas D-dimer
concentration did. CONCLUSION: The determination of TAT and F1 + F2 in venous
blood does not adequately reflect the degree of the local coagulation activation
in the arterial system. As indicators for hypercoagulability, D-Dimer values are
less sensitive than F1 + 2, but venous D-dimer concentrations mirror arterial
levels.
PMID- 10191701
TI - Bioelectrical impedance sphygmography for hydrostatic toe pressure measurement: a
new non-invasive method to assess limb ischaemia.
AB - BACKGROUND: Hydrostatic measurement of systolic toe blood pressure (HSTBP) is
reliable in feet with calcified arteries, when sphygmomanometry fails. When leg
is lifted above heart level, weaning of the big toe's arterial pulsations
indicates HSTBP. PATIENTS AND METHODS: Electrical bio-impedance was assessed to
monitor the weaning of arterial pulsations (Medis GmbH, Ilmenau, Germany). In a
pilot study in 30 healthy volunteers, a 12 cm cuff was placed above the ankle and
inflated to 200 mmHg; ultrasound (8 MHz) and impedance sphygmography (ISG) were
used simultaneously to detect arterial pulsations in the big toe, in the sitting
and supine position after deflating the cuff. In a clinical study, HSTBP was
assessed by big toe ISG in 50 legs (43 of diabetic patients) with suspected
peripheral arterial occlusive disease, subjected to arteriography before vascular
surgery. RESULTS: In the pilot study, ultrasound and ISG signals were detected at
nearly identical systolic pressure levels (difference 2.4 [SEM 0.6] mmHg, r =
0.99, p < 0.001). In the clinical study, HSTBP < or = 50 mmHg was associated with
multiple occlusions (2 legs with < or = 1, 9 legs with 2, and 13 legs with > 2
arteries occluded); by contrast, HSTBP > 50 mmHg indicated single occlusions (16
legs with < or = 1, 8 legs with 2, and 2 legs with > 2 occluded arteries; chi 2
contingency p < 0.02). CONCLUSIONS: Assessment of big toe arterial pulsation by
ISG was reliable. HSTBP < or = 50 mmHg indicates severe peripheral arterial
disease occlusive (> or = 2 arteries occluded).
PMID- 10191702
TI - Effect of different compression therapies on the reflux in deep veins with a post
thrombotic syndrome.
AB - BACKGROUND: Reflux in deep veins is an important pathophysiological factor of
post-thrombotic syndrome which can be demonstrated by colour-coded
duplexsonography. This study investigates the effect of different compression
therapies on the reflux velocity in deep veins in patients with a post-thrombotic
syndrome. PATIENTS AND METHODS: Sixty patients with a post-thrombotic syndrome
confirmed by phlebography, in the deep veins of the calf and the thigh were
investigated in two groups: In group A, 30 patients (mean age 58 +/- 10 years)
received compression stockings (calf compression class II and III, thigh
compression class II) and in group B 30 patients (mean age 58 +/- 14 years)
received a Sigg short traction bandage of the calf. The velocity at the time of
the greatest reflux in the popliteal vein was determined as reflux parameter with
the colour-coded duplex sonography using a cuff applied at the calf. All patients
stood upright and were measured with and without different kinds of compression
therapies. The reflux velocities were graded as low, moderate and high. RESULTS:
A significant decrease of the reflux velocity by about more than 45% with
compression therapy was found in both groups. The decrease of the refluxes in
group A (mean 47.9%) did not differ significantly from the decrease of refluxes
in group B (mean 55.8%). The greatest decrease of the reflux velocity under
compression therapy was found in high-grade refluxes in both groups. CONCLUSION:
A significant decrease of the reflux velocity in post-thrombotic syndrome can be
readily demonstrated with different kinds of compression stockings as well as
with bandages by means of colour-coded duplex sonography.
PMID- 10191703
TI - Relevance of claudication pain distance in patients with peripheral arterial
occlusive disease.
AB - BACKGROUND: Determination of both the pain-free and the maximum walking distances
is part of a routine program in the angiological examination of patients with
PAOD. It is however as yet not clear which of these two parameters is more
relevant in determining a patient's pathological condition. PATIENTS AND METHODS:
In 150 patients with stable intermittent claudication, the claudication pain
distance (CPD) and the maximum pain distance (MPD) were determined on a treadmill
at 3.0 km/h and 12% inclination. The results were compared with the angiographic
findings, the Doppler pressure values and the subjective quality of life (PAVK-86
Questionnaire). RESULTS: The average pain-free walking distance was 89 +/- 71 m,
and the maximum walking distance was 198 +/- 141 m. There was no correlation
between both walking distances and the angiographic extent of PAOD. Only the MPD
correlated with the ankle systolic Doppler pressure and the ankle/brachial
pressure index of the claudicating leg (r = 0.16, p < 0.05 and r = 0.20, p <
0.01). Both the CPD and the MDP had a significant influence on the life quality
of the patients (CPD: r = -0.41, p < 0.001; MPD: r = -0.47, p < 0.001). In the
multiple regression analysis, beside the body mass index, the MPD was found to be
the greatest predictor for the pathologically relevant quality of life dimensions
pain, complaints and functional status. CONCLUSIONS: The maximum walking distance
correlated in a better way than pain-free walking distance with the objective and
subjective assessment criteria of PAOD. Therefore, as regards the stage of the
disease and the life quality of the patient, this parameter has a greater
importance. This fact deserves to receive greater attention in everyday clinical
practice and when conducting clinical trials.
PMID- 10191704
TI - Ruptured infrarenal aortic aneurysm--a critical evaluation.
AB - BACKGROUND: Objective evaluation of the management of patients with ruptured
infrarenal aortic aneurysm in emergency situations has been described rarely.
PATIENTS AND METHODS: Fifty-two consecutive patients with ruptured infrarenal
aortic aneurysm (mean age, 70.3 years; range, 56-89 years; SD 7.8) were admitted
between January 1993 and March 1998. Emergency protocols, final reports, and
follow-up data were analyzed retrospectively. APACHE II scores at admission and
fifth postoperative day were assessed. RESULTS: The time between the appearance
of first symptoms and the referral of patients to the hospital was more than 5
hours in 37 patients (71%). Thirty-eight patients (71%) had signs of shock at
time of admission. Ultrasound was performed in 81% of patients as the first
diagnostic procedure. The most frequent site of aortic rupture was the left
retroperitoneum (87%). Intraoperatively, acute left ventricular failure occurred
in four patients, and cardiac arrest in two others. The postoperative course was
complicated significantly in 34 patients. The overall mortality rate was 36.5% (n
= 19). In 35 patients, APACHE II score was assessed, showing a probability of
death of more than 40% in five patients and lower than 30% in 17 others. No
patient showing probability of death of above 75% at the fifth postoperative day
survived (n = 7). CONCLUSIONS: Ruptured aortic aneurysm demands surgical
intervention. Clinical outcome is also influenced by preclinical and anesthetic
management. The severity of disease as well as the patient's prognosis can be
approximated using APACHE II score. Treatment results of heterogeneous patient
groups can be compared.
PMID- 10191705
TI - The importance of graft blood flow and peripheral outflow resistance for early
patency in infrainguinal arterial reconstructions.
AB - BACKGROUND: At present, the importance of functional parameters as determinants
for graft patency is under debate. Therefore, in our institution a prospective
study was undertaken to evaluate the influence of graft blood flow as well as the
currently applied methods for outflow resistance measurement on early (< or = 30
days) graft outcome. PATIENT AND METHODS: 101 arterial revascularisations with
infrageniculate graft insertion were entered into this study. After having
verified the morphological integrity of the reconstruction, during temporary
inflow occlusion total outflow resistance (TOR) was determined as a pressure/flow
relationship by perfusion of the graft with saline (flow rates 25, 50, 100, 150
ml/min before and after papaverine) while simultaneously recording pressure
generated at the distal anastomosis. In addition, after restoration of blood
flow, flow index (FI) was calculated in an analogous way from the TBF through the
graft and the respective mean distal anastomotic pressure. Graft patency at 30
days was determined by Duplex ultrasound. RESULTS: Functional parameters were
found to be unable to differentiate between patent and failed reconstructions
during the 30 day period: The mean TORaveraged values amounted to 722.5 (SD =
310) in patent and 735.9 (SD = 228.1) mPRU in occluded bypasses (T-value =
0.1681; n.s.). The corresponding figures were 176.8 (SD = 94.2) and 196.4 (SD =
93.6) ml/min for TBF (T-value = 0.7342; n.s.) and were 0.53 (SD = 0.34) and 0.45
(SD = 0.25) PRU for FI (T-value = 0.8905; n.s.). Using multiple logistic
regression analysis functional parameters showed no influence on graft patency
while graft length and the necessity for intraoperative graft modification
emerged to be significant determinants of early graft outcome (R2 adjusted =
0.46; p = 0.006). CONCLUSION: The results of our study suggest that neither blood
flow nor the presently used methods to assess outflow resistance are relevant
prognostic factors for early (< or = 30 days) graft performance.
PMID- 10191706
TI - Aortobifemoral prosthetic infection treated by cryopreserved arterial homografts
of the European Homograft Bank.
AB - The excision of an infected aortobifemoral Dacron graft 9 years after
implantation and bilateral axillofemoral Dacron bypass reconstruction led to
reinfection of the extra-anatomic bypass grafts. A new aortobifemoral
reconstruction was performed using cryopreserved homografts delivered by the
European Homograft Bank in Brussels and both axillo-femoral prostheses were
removed. No signs of infection and no alterations of the homografts can be
detected 3 years later.
PMID- 10191707
TI - Spontaneous reversibility of early reobstruction following percutaneous
transluminal angioplasty.
AB - Early reocclusion and late restenosis are well-known problems after percutaneous
transluminal angioplasty (PTA). We report here on a phenomenon not described so
far in two patients with peripheral arterial occlusive disease who had PTA of the
common iliac and the superficial femoral artery, respectively. Both had a good
hemodynamic and clinical initial result. However, within two days after PTA
symptomatic reobstruction occurred documented by noninvasive measurements.
Noteworthy, this reobstruction was spontaneously reversible within days. The
possible pathomechanism is discussed.
PMID- 10191708
TI - [Symptomatic abdominal aortic aneurysm and left-sided infrarenal vena cava].
AB - Coincidence of an abdominal aortic aneurysm and abnormalities of the inferior
vena cava is a rare condition but has significance for surgical therapy. By the
preoperative use of various imaging techniques and adapted surgical procedure the
risk of the operation is decreasing to a minimal level. A case of symptomatic
abdominal aneurysm and left-sided infrarenal vena cava is presented and the
importance of preoperative examinations and operative strategy is discussed.
PMID- 10191709
TI - Placement of a pulmonary artery catheter via a previously unrecognized persistent
left superior vena cava.
AB - This case report describes a patient with persistent left superior vena cava
(LSVC) as discovered by difficult placement of a pulmonary artery catheter via
the left subclavian vein. After positioning in wedge position, chest x-ray showed
a catheter route suggestive of persistent LSVC. Since this abnormality may yield
potential clinical complications, this possibility should be considered in every
difficult central venous access.
PMID- 10191711
TI - Andreas Gruntzig's balloon catheter for angioplasty of peripheral arteries (PTA)
is 25 years old.
AB - History of Andreas Gruntzig's time spent in Angiology and Radiology of the Zurich
University Hospital (1969-1975). First, the pioneer of catheter therapy
discovered that the Achilles tendon reflex is significantly prolonged during
claudication pain. Furthermore, he participated actively in the clinical
evaluation of Doppler ultrasound. After a stay in the Aggertalklinik
(Engelskirchen near Koln, Germany), where he learnt Charles Dotter's original
procedure with Eberhard Zeitler, he introduced catheter therapy of peripheral
arteries in Zurich. In the same period he developed a new, rigid, sausage-shaped
balloon catheter (polyvinylchloride), manufactured the device on his kitchen
table together with his wife Michaela, Maria and Walter Schlumpf, and used it
first on February 12, 1974 in a patient with intermittent claudication due to
subtotal stenosis of the superficial femoral artery. The first successful
dilatation of an iliac artery stenosis by his double-lumen catheter, which was
modified later on into the famous coronary catheter, followed on January 23,
1975. Soon, the innovative catheter became commercially available (Cook and
Schneider Companies). Andreas Gruntzig not only excelled in pioneering novel
techniques, but also in patient care, in a prospective follow-up study of his own
242 patients lasting 15 years (results summarized in this article), in the
teaching of Swiss scholars like Felix Mahler, Ernst Schneider and Bernhard Meier
and many more in the world, and in organizing life demonstrations for large
numbers of participants. His career in Cardiology, his work in Atlanta Georgia,
USA, and his early tragic death in an airplane accident are briefly mentioned.
PMID- 10191710
TI - Abdominal pulsatile tumor after endovascular abdominal aortic aneurysm repair.
AB - A 70 years old patient was successfully treated for infrarenal aortic aneurysm by
an endovascular bifurcated prosthesis. Three months later, because of dysuria, he
underwent urological examination revealing an abdominal pulsatile tumor.
Thereafter, the patient was sent to our emergency ward with suspected
symptomatical endoleak. Radiological screening by computer tomography and
magnetic resonance angiography showed good post-operative results without
endoleak. Patient was treated with antispasmodic medication and is doing well
today. Because endovascular repair of aortic aneurysm, in contrast to an open
approach, does not eliminate the aneurysm itself, post-operative abdominal
palpation can be ambiguous. Magnetic resonance angiography--without the need of
nephrotoxic contrast medium--compares favourably to CT and provides excellent
pictures with less artefacts for post-operative screening of endoleak. If
reperfusion can be excluded, pulsation is due to the transmission of the blood
pressure wave to the thrombosed aneurysm.
PMID- 10191712
TI - [Distal femoro-popliteal bypass using Esmarch regional ischemia. Is evaluation of
the method adequate? An opposing comment].
PMID- 10191713
TI - Novel antiinflammatory analgesics: 3-(2-/4-pyridylethyl)-benzoxazolinone and
oxazolo[4,5-b]pyridin-2-one derivatives.
AB - Twenty-two new 3-[2-(2-and/or 4-pyridyl)ethyl]benzoxazolinone and oxazolo[4,5
b]pyridin-2-one derivatives have been synthesized by reacting 2- and/or 4
vinylpyridine and appropriate benzoxazolinones and oxazolo[4,5-b]pyridine-2-one.
Their chemical structures have been proven by IR. 1H-NMR, 13C-NMR, mass
spectroscopy, and elemental analysis. The analgesic activities of these compounds
were investigated by a modified Koster's Test. Test results revealed that, at 100
mg/kg dose level, most of the compounds showed significant analgesic activities
when compared to aspirin. Therefore the compounds were screened for their
antiinflammatory activities using the carrageenan hind paw edema test. Compounds
1, 7, 10, 11, 12, 13, 15, 18, 20, 21 were found more active than indomethacine.
In gastric ulceration studies gastrointestinal bleeding was not observed at 100
mg/kg dose level in compounds 1 and 2.
PMID- 10191714
TI - Synthesis and pharmacological activities of novel 3-(isoxazol-3-yl)-quinazolin
4(3H)-one derivatives.
AB - Several new 3-(isoxazol-3-yl)-quinazolin-4(3H)-one derivatives were synthesized
and tested for their analgesic and antiinflammatory activities, as well as for
their acute toxicity and ulcerogenic effect. A few compounds were as active as
phenylbutazone in the writhing and acetic acid peritonitis tests. They had a very
low ulcerogenic effect.
PMID- 10191715
TI - New synthesis of substituted 2-carboxyindole derivatives: versatile introduction
of a carbamoylethynyl moiety at the C-3 position.
AB - A novel series of 3-carbamoylethynyl-2-carboxyindoles, antagonists acting at the
strychnine-insensitive glycine binding site associated with the NMDA receptor,
has been synthesised. This new versatile approach involves the introduction of a
2-chloroethenyl moiety in position C-3 with subsequent derivatisation of the
terminal carboxyl group, followed by an unusual elimination of HCl to afford the
ethynyl functionality. This novel series of glycine antagonists was evaluated in
terms of in vitro affinity at the glycine binding site and the most potent
compound was tested in vivo in the NMDA-induced convulsions model in mice.
PMID- 10191716
TI - [meso-1,2-bis(2,6-dichloro-4-hydroxyphenyl) ethylenediamine]dichloroplatinum(II),
a compound with a specific activity on hormone-sensitive breast cancers--evidence
for a diethylstilbestrol-like mode of action.
AB - [meso-1,2-Bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine]- dichloroplatinum(II)
(meso-1-PtCl2), an estrogenic and cytotoxic platinum complex, shows activity
against ER+ but not against ER- breast cancers in vivo (ER: estrogen receptor;
ER+ and ER- indicate the presence or absence of the ER). To clarify whether its
estrogenic or its cytotoxic potency or both properties are the cause of this
specific inhibitory effect, we tested meso-1-PtCl2 comparatively in vivo on an
ER+ and an ER- murine breast cancer (MXT-M-3.2 MC and MXT-M-3.2(ovex) MC,
respectively), and in vitro on two cell lines derived from the former in vivo
models (MXT+ and MXT-, respectively). The estrogens diethylstilbestrol (DES) and
the ligand of meso-1-PtCl2 (meso-1), responsible for the hormonal effect of meso
1-PtCl2, and the cytotoxic drug cisplatin (cDDP) were used as comparative
substances. Meso-1-PtCl2. DES and cDDP showed a strong and comparable activity on
the ER+ MXT-M-3.2 MC in vivo, meso-1 being somewhat less inhibitory. In
experiments on the murine, ER- MXT-M-3.2(ovex) MC only cDDP caused a marked
inhibitory effect. The other compounds were inactive or only marginally active.
In accordance with the in vivo results cDDP was also very active on the MXT+ and
MXT- breast cancer cell line. In contrast to this meso-1-PtCl2, meso-1, and DES
proved to be only weakly active or inactive on both cell lines. From these
results it can be concluded that there is only little if any contribution of the
cytotoxic PtCl2 moiety of meso-1-PtCl2 to the anti-breast cancer activity in
vivo. On the ER+ MXT-M-3.2 MC transplanted into ovariectomized mice meso-1-PtCl2
yielded a biphasic dose activity curve, i.e. an increase of the tumor growth at
low doses followed by a decrease at high doses, identical with those of the
estrogens DES and meso-1. These results indicate that meso-1-PtCl2 inhibits ER+
breast cancers by its estrogenicity in the same manner as meso-1 and DES. The
complex mechanism of anti-breast cancer active estrogens involves presumably the
endocrine and/or the immune system. Its investigation is the subject of further
studies.
PMID- 10191717
TI - Suppressor genes with gender differences in activity in natural populations of
Drosophila robusta: another approach to wild-type.
AB - Homozygous or hemizygous expression of an X-linked wing mutant of Drosophila
robusta varies from a rudimentary wing that does not reach the tip of the abdomen
(called 'club') to forms with full-sized but curled or crumpled wings (called
'curly'). Homozygous club females crossed to flies from natural populations or
laboratory stocks derived from wild flies invariably produce significantly less
club male progeny than the 100% expected, most of them exhibiting less severe
phenotypes: 'curly' forms and wild-type. The male progeny from similar crosses
using curly females tend to be predominantly normal. By contrast, the male
progeny of outcrossed females homozygous for an X-linked eye colour mutant,
vermilion, are all vermilion. The data indicate that natural populations of D.
robusta contain suppressors of the wing mutant but not of the eye colour mutant
studied. Activity of the suppressors differs by gender: in experiments in which
genetic theory expects similar results in the two sexes, males consistently show
stronger effects of the suppressors than females.
PMID- 10191718
TI - Linkage disequilibrium, mutational analysis and natural selection in the
repetitive region of the clock gene, period, in Drosophila melanogaster.
AB - We have used the method of disequilibrium pattern analysis to examine
associations between the threonine-glycine (Thr-Gly) encoding repeat region of
the clock gene period (per) of Drosophila melanogaster, and polymorphic sites
both upstream and downstream of the repeat, in a number of European fly
populations. The results are consistent with the view that selection may be
operating on various haplotypes which share the Thr-Gly length alleles encoding
17, 20 and 23 dipeptide pairs, and that the repeat itself may be the focus for
selection. These conclusions lend support to a number of other population and
behavioural investigations which have provided evidence that selection is acting
on the Thr-Gly region. The linkage analysis was also used to infer an approximate
mutation rate (mu) for the repeat, of 10(-5) < mu < 4 x 10(-5) per gamete per
generation. Direct measurements of the mutation rate using the polymerase chain
reaction in a pedigree analysis of tens of thousands of individuals do not
contradict this value. Consequently, the Thr-Gly repeat does not have a mutation
rate that is as high as some of the non-coding minisatellites, but it is several
orders of magnitude higher than the nucleotide substitution rate. The
implications of this elevated mutation rate for linkage disequilibria and
selection are discussed.
PMID- 10191719
TI - Cell-cycle-specific transcription termination within the human histone H3.3 gene
is correlated with specific protein-DNA interactions.
AB - In vitro studies using highly purified calf thymus RNA polymerase II and a
fragment spanning the first intron of H3.3 as template DNA have demonstrated the
existence of a strong transcription termination site consisting of thymidine
stretches. In this study, nuclear run-on experiments have been performed to
assess the extent to which transcription elongation is blocked in vivo using DNA
probes corresponding to region 5' and 3' of the in vitro termination sites. These
studies suggest that H3.3 expression is stimulated following the inhibition of
DNA synthesis through the elimination of the transcription elongation block.
Interestingly, both the in vivo and in vitro experiments have revealed that the
transcriptional block/termination sites are positioned immediately downstream of
a 73 bp region that has been over 90% conserved between the chicken and human
H3.3 genes. The extreme conservation of this intronic region suggests a possible
role in maintaining cis-acting function. Electrophoretic mobility shift
experiments show that HeLa cell nuclear extracts contain protein factors that
bind specifically to the region of transcription elongation block. Furthermore,
we demonstrate a correlation between the protein binding activity and the
transcriptional block in cells that have been either arrested at the initiation
of S phase or were replication-interrupted by hydroxyurea. DNA footprinting
experiments indicate that the region of protein binding is at the 3' end of the
conserved region and overlaps with one of the three in-vitro-mapped termination
sites.
PMID- 10191720
TI - On the estimation of ancestral population sizes of modern humans.
AB - The theory developed by Takahata and colleagues for estimating the effective
population size of ancestral species using homologous sequences from closely
related extant species was extended to take account of variation of evolutionary
rates among loci. Nuclear sequence data related to the evolution of modern humans
were reanalysed and computer simulations were performed to examine the effect of
rate variation on estimation of ancestral population sizes. It is found that the
among-locus rate variation does not have a significant effect on estimation of
the current population size when sequences from multiple loci are sampled from
the same species, but does have a significant effect on estimation of the
ancestral population size using sequences from different species. The effects of
ancestral population size, species divergence time and among-locus rate variation
are found to be highly correlated, and to achieve reliable estimates of the
ancestral population size, effects of the other two factors should be estimated
independently.
PMID- 10191721
TI - A prescription for irony.
PMID- 10191722
TI - Location, location. Sleepless in Pa.
PMID- 10191723
TI - Eyewitness. Survivor's skill.
PMID- 10191724
TI - Discount fallout. Hammered & nailed.
PMID- 10191725
TI - Privileges. Stints that sting.
PMID- 10191726
TI - Staff stretch. Home remedy.
PMID- 10191727
TI - Does the Joint Commission add value?
PMID- 10191728
TI - Pay flap. Lone Star wars.
PMID- 10191729
TI - Skills vs. seniority: the logic of layoffs.
PMID- 10191730
TI - Innovations. Card smarts.
PMID- 10191731
TI - The price of dignity.
PMID- 10191732
TI - Al wants more hair, less fat, and a better sex life ... and he wants his health
plan to pay for it.
AB - Al wants a trimmer waistline. Hanna wants the surgery that will give her ears,
which she was born without. Both think their HMOs should pay. Hanna and Al are at
the limits of the emerging gray zone between medical need and medical want. It's
a zone sure to become grayer, as medicine strays even further into the murkey
region of lifestyle enhancement.
PMID- 10191733
TI - Net profits.
AB - As Web traffic surges, health care has become a speed zone all its own. Sixth in
Internet content, health sites draw two-thirds of all online users at least once.
That's set off a race among the developers of specialized hubs aiming to organize
it all--and cash in. "It's a land grab," says one player. "All of a sudden
everyone woke up and said, 'We gotta do this.'"
PMID- 10191734
TI - Hospital projects whose designers and builders know how to get along. The VISTA
Awards.
AB - The customer is the big picture for all three teams honored with 1998-99 VISTA
Awards for innovative construction. Their tasks couldn't have differed more: a
new VA medical center in Michigan, a children's hospital in Texas, and a major
hospital addition in Oregon. What unites them is a team spirit and sense of
partnership behind their success.
PMID- 10191735
TI - Boom vs. bust.
AB - Bad luck, bad timing, bad management: Whatever the cause, many of yesterday's
Wall Street highfliers have crash-landed. Our Executive Chartbook takes a look at
some of health care's current stock leaders, weighing out why they might--or
might not--fall in the months ahead.
PMID- 10191736
TI - Everywhere a sign.
PMID- 10191737
TI - Norian SRS versus external fixation in redisplaced distal radial fractures. A
randomized study in 40 patients.
AB - We compared Norian SRS, an injectable calcium phosphate bone cement, with
external fixation in the treatment of redisplaced distal radial fractures by a
prospective randomized study in 40 patients (women 50-80 years or men 60-80
years). After rereduction, the fracture was either stabilized by injection of SRS
and immobilized with a cast for 2 weeks, or externally fixed with Hoffman's bar
for 5 weeks. Each patient was evaluated at 2, 5, 7 weeks and at 3, 6 and 12
months. Functional parameters were grip strength, range of motion and pain.
Radiographic parameters were radial angle, ulnar variance and dorsal tilt. The
chosen primary effect variable was grip strength at 7 weeks. Patients treated by
injection of SRS apatite had better grip strength, wrist extension and forearm
supination at 7 weeks. There was no difference in functional parameters at 3
months or later. None of the methods could fully stabilize the fracture:
radiographs showed a progressive redislocation over time. The results indicate
that SRS can be used in the treatment of unstable distal radial fractures. The
more rapid recovery of grip strength and wrist mobility in the SRS group appears
to be due to the shorter immobilization time.
PMID- 10191738
TI - No stabilizing effect of the elbow joint capsule. A kinematic study.
AB - We dissected 7 cadaveric elbow specimens, leaving the collateral ligaments and
the joint capsule intact. The anterior and the posterior capsule were
sequentially transected, followed by kinematic testings. We found no change in
joint laxity after total transection of the capsule.
PMID- 10191739
TI - The position of the axillary nerve in the deltoid muscle. A cadaveric study.
AB - In 134 deltoid preparations taken from 67 fresh cadavers we examined the position
of the axillary nerve in relation to the upper border of the muscle. The vertical
distances from the upper deltoid border to the nerve in 17 of 67 cadavers was
less than 4 cm in both shoulders. The minimal distance, measured from the mid
middle portion of the deltoid to the axillary nerve, was 2 cm. There was a
significant negative correlation between the deltoid ratio (width/length) and the
vertical distance, measured in all examined sites. The shorter the deltoid length
the greater the danger of damaging the nerve in the short distance during
surgical splitting of the muscle.
PMID- 10191740
TI - The effect of hospital-type and operating volume on the survival of hip
replacements. A review of 39,505 primary total hip replacements reported to the
Norwegian Arthroplasty Register, 1988-1996.
AB - We investigated associations between the survival of total hip replacements
(THRs), type of hospital and annual number of THRs per hospital. The study was
based on 39,505 primary THRs reported to the Norwegian Arthroplasty Register from
45 local (n 20,756), 15 central (n 12,455) and 10 university hospitals (n 6,294)
during 1988-1996. The annual number of THRs was highest at central and university
hospitals, both of which are training hospitals. University hospitals were
further characterized by the lowest mean annual number of THRs performed per
surgeon. For cemented THRs, with adjustment for gender, age, diagnosis, surgical
procedure, and annual hospital volume, the revision rates at central and
university hospitals were 0.8 (95% confidence interval: 0.67-0.95) and 1.2 (CI:
1.02-1.47) times that of local hospitals, respectively. A high annual number of
cemented THRs per hospital was not associated with lower revision rates. In
uncemented THRs, survival results were similar in central and local hospitals,
whereas the adjusted revision rate at university hospitals was 1.6 (CI: 1.13
2.19) times that of local hospitals. The adjusted 6.5 year revision probability
was 12% in hospitals performing < or = 10 uncemented THRs per year (n 606), 8% in
hospitals performing from 18-28 operations (n 1,378) and 5% in hospitals
performing > 84 operations (n 526).
PMID- 10191741
TI - Incidence of hip fractures in Malmo, Sweden, 1992-1995. A trend-break.
AB - The incidence of hip fractures in Malmo, Sweden, has been studied since 1924.
Predictions based on material from the 1950s to the 1980s have shown an almost
exponential increase in incidence. During 1992-1995, 2,268 patients aged 50 and
older, with hip fractures, were admitted to Malmo University Hospital, the only
hospital in the city treating hip fractures. 76% were women with a mean age of 81
(SD 8) years, and the mean age of men was 78 (SD 9) years. 47% of the fractures
were cervical. The annual incidences per 10,000 inhabitants were 36 in men and 85
in women. The corresponding numbers of subjects over 80 years were 170 men and
297 women. These findings show that the incidence is no longer increasing. The
causes of such a trend-break could be successful osteoporosis prevention, an
increasing proportion of non-Scandinavian immigrants with a lower genetic risk of
osteoporotic fractures, or a healthier elderly population. Increasing number of
the population at risk already have two operated hips, due to previous fractures
or arthrosis. Other causes may be fewer prescriptions of sedatives and higher
winter temperatures.
PMID- 10191742
TI - Diathermy knife does not reduce bleeding in surgery for primary hip arthroplasty.
A prospective randomized study of 67 patients.
AB - We evaluated bleeding in a prospective randomized study of 67 patients undergoing
primary hip arthroplasty. In group A, all dissections were made with the
diathermy knife and in group B, we used the scalpel. In both groups, bleeding
points were coagulated with diathermy. The surgical approach, use of anti
coagulants and method of anesthesia were similar in the two groups. We found that
use of a diathermy knife does not significantly reduce bleeding.
PMID- 10191743
TI - Impaction bone-grafting increases the holding power of cancellous screws in the
femoral head. A pull-out study in human cadaver hips.
AB - We studied the effect of impaction of fresh cancellous bone or demineralized bone
matrix (DBM) around cancellous screws in 25 cadaver femoral heads. The bone
mineral content (BMC) of femoral heads was measured to determine if greater
relative increase in holding power will be achieved by impaction-grafting, as the
BMC of the specimen decreases. A 60% (p < 0.001) relative increase in the pull
out force was achieved by impaction-grafting with DBM, compared to non-grafted
controls. The augmenting effect of fresh cancellous bone graft and DBM did not
differ significantly. The relative improvement in holding power was not inversely
correlated to femoral head BMC, but was inversely related to the pull-out
resistance of non-grafted control screws. These findings suggest that impaction
grafting provides significantly better hold of cancellous screws in femoral
heads.
PMID- 10191744
TI - Unreamed intramedullary nailing for pathological femoral fractures. Good results
in 30 cases.
AB - We have used the AO unreamed femoral nail for stabilization of impending and
complete pathological fractures since March 1994. 27 patients with 30
pathological fractures (23) or impending fractures (7) of the femur were
retrospectively analyzed. These included 18 subtrochanteric fractures, 11 shaft
fractures and 1 distal fracture. The mean age of the patients was 68 (51-84)
years. All patients were treated with a solid femoral nail inserted by an
unreamed technique. The nail was inserted through a minimally invasive approach
and with a median surgical time of 55 (35-70) minutes. A reconstructive proximal
locking option (spiral blade) was used in 25 cases. There were no intraoperative
complications, no operative mortality. Reliable skeletal stability was obtained
in all cases and most were able to mobilize early with minimum discomfort. 1 case
was revised for a secondary fracture through a distal metastasis at 6 months. The
median survival was 5 (2-9) months. Unreamed nailing with the AO solid femoral
nail appears to be a good option for the stabilization of pathological femoral
fractures.
PMID- 10191745
TI - Nonunion and shortening after femoral fracture treated with one-stage lengthening
using locked nailing technique. Good results in 48/51 patients.
AB - We report on 56 consecutive aseptic femoral shaft nonunions with shortening,
which were treated with local debridement, skeletal traction, a spine-spreader
aiding lengthening, static locked nail stabilization and corticocancellous bone
grafting. 51 patients were followed for 2 (1-4) years and 48 achieved a solid
union. The median period to bony union was 4 (3-8) months and lengthening
achieved was 2.8 (1.5-4.5) cm. 3 patients had nonunion, 2 without implant failure
and 1 with implant failure. However, all 3 healed after reoperation. There was no
neurovascular injury or deep infection.
PMID- 10191746
TI - The external spinal fixator does not reduce anterior column motion under axial
compressive loads. A mechanical in vitro study.
AB - We performed an in vitro study to investigate the effect of external spinal
fixation on anterior column motion under physiological axial compression loading.
The AO external spinal fixator (ESF) was applied to 5 human cadaveric lumbar
spine specimens (L3-S1) at levels L4 to S1. All specimens were tested in 4
configurations: i) intact, ii) ESF in a neutral position, iii) ESF in distraction
(12 mm), and iv) ESF in compression (8-12 mm). Cyclic sinusoidal axial
compressive loads from 60 to 600 N were applied for 10 cycles in each test
condition. The axial displacement of the load application point was recorded as
an indicator of anterior column axial translation. The axial motion with the
fixator in distraction was significantly greater than all other conditions,
including intact. Compression of the fixator resulted in the least axial
displacement. External fixation in the neutral position did not significantly
affect the overall axial translation, when compared to the intact state. In
conclusion, the external spinal fixator did not significantly reduce anterior
column axial translation and, in distraction, this motion exceeded that of the
intact specimen. Since pain relief is frequently observed during distraction of
the painful segment/s with the external fixator, the mechanical basis of the pain
relief is not well understood.
PMID- 10191747
TI - Can an external frame fixation reduce the movements in the sacroiliac joint? A
radiostereometric analysis of 10 patients.
AB - To evaluate whether a Hoffmann-Slatis frame can reduce movements in the
sacroiliac joints, 10 patients (7 women) with severe posterior pelvic pain of
long duration were externally stabilized. The movements were analyzed with
radiostereometric analysis (RSA) in supine and standing positions, preoperatively
and postoperatively with the frame applied. In 2 patients, there was no reduction
in the movements with the frame, perhaps because it was not properly tightened.
In the remaining 8 patients, the median reduction in rotation was 55% on the left
side and 63% on the right side around the helical axes, and 74% around the x-axes
on the left side and 66% on the right side. Our data suggest that external
fixation using the Hoffmann-Slatis frame, substantially reduces sacroiliac joint
mobility in some patients, which must be considered when using the frame as a
diagnostic tool. Pre-stressing the frame by tightening the vertical bars before
the compression bar is applied is recommended to reduce the risk of this
shortcoming.
PMID- 10191748
TI - No influence of large volume blood loss on serum vancomycin concentrations during
orthopedic procedures.
AB - We prospectively studied orthopedic patients with either large or small blood
loss who also received vancomycin prophylaxis to determine the effect of
intraoperative volume shifts on serum vancomycin concentrations. There were 6
index patients in the large blood loss group (greater than 2 L), and 7 in the
control group (less than 2 L). Mean estimated blood loss for index and controls
was 4.4 L and 1.0 L, respectively. Mean intraoperative fluid resuscitation,
excluding blood products, was 12.4 L and 5.1 L, respectively. There was a modest
inverse correlation between blood loss and intraoperative serum half-life of
vancomycin. Although controls maintained slightly higher intraoperative
vancomycin concentrations at each time-point, there was no statistically
significant difference between the groups with regard to absolute concentrations
or rate of decline. After 8 hours, the serum vancomycin concentration exceeded
the MIC-90 for Staphylococcus aureus by approximately eightfold in all but one
case patient. This was a morbidly obese patient with massive blood loss. Thus,
blood loss during orthopedic procedures has minimal effects on intraoperative
kinetics of vancomycin. Redosing is rarely indicated, although a preoperative 1.5
gram-dose should be considered for patients weighing more than 90 kg.
PMID- 10191749
TI - Enhanced tendon healing with GDF 5 and 6.
AB - Between ruptured tendon ends, undifferentiated mesenchymal cells invade the
hematoma and differentiate to form a tendon regenerate. This differentiation is
partly directed by mechanical stimuli, which are difficult to apply and control
clinically. For example, closed treatment of Achilles tendon ruptures is
associated with a risk of rerupture of the regenerate. Improved tendon healing by
exogenous growth factors has not previously been reported. Three proteins in the
Bone Morphogenetic Protein (BMP) family--namely Growth and Differentiation
Factors (GDFs) 5, 6 and 7--have recently been shown to induce a tendon- or
ligament-like tissue after intramuscular implantation in rats, indicating a new
way to improve tendon healing. We transected the Achilles tendon in 66 rats and
denervated the calf muscle. Denervation served to reduce the mechanical
stimulation to the tendon callus by eliminating muscle contractions. GDF 5 or 6
were implanted on collagen sponges in the tendon defects in two doses and
compared to collagen sponges alone. The rats were killed after 2 weeks and the
tensile strength of the tendon regenerate was found to be increased by both
proteins in a seemingly dose-dependent manner.
PMID- 10191751
TI - Early muscle-periosteal lesion inhibits fracture healing in rats.
AB - We assessed the effects of muscular detachment from the periosteum on fracture
healing, focusing on a muscle-periosteal lesion in the initial healing process.
In 30 male Wistar rats we produced a partial osteotomy in the mid-diaphysis of
the left femur which was then manually broken. All fractures were reamed and
stabilized with a 1.6 mm steel pin. The animals were randomly assigned to 3
groups. In group 1, an extraperiosteal detachment between muscle and periosteum
was created in the middle third of the diaphysis. In group 2, an extraperiosteal
detachment was created with application of an ePTFE sheath (Gore-Tex expanded
polytetrafluoroethylene) around the shaft between muscle and periosteum during
the first 2 weeks following fracture. In group 3, the dissection was identical,
while the ePTFE sheath was installed after 2 weeks. The rats were killed after 4
weeks, and their bones were evaluated radiographically and mechanically by the
three-point bending test. The fractures healed by production of external callus,
and radiographs revealed various degrees of periosteal callus with a radiolucent
fracture line, most evident after early muscle-periosteal isolation. The callus
area was significantly smaller after early muscle isolation, compared to
extraperiosteal dissection alone and later tissue isolation. Bending moment and
stiffness were also less in this group than in groups 1 and 3, while fracture
energy was less than in group 1. No differences in mechanical properties were
detected between extraperiosteal dissection alone and late-tissue isolation. This
animal study underlines the importance of early muscle-periosteal apposition for
fast periosteal healing of diaphyseal fractures.
PMID- 10191750
TI - Optimization of chondrocyte expansion in culture. Effect of TGF beta-2, bFGF and
L-ascorbic acid on bovine articular chondrocytes.
AB - In vitro multiplication of isolated chondrocytes is needed to repair articular
cartilage defects with autologous material. In this study we used monolayer
cultures of bovine articular chondrocytes. The effect of transforming growth
factor beta-2, basic fibroblast growth factor or L-ascorbic acid on cell
multiplication, in the presence of 10% fetal calf serum, was measured in primary
culture, the third and tenth passage. TGF beta-2 stimulated the proliferation of
chondrocytes in the primary culture and L-ascorbic acid stimulated in the third
passage. On the basis of these results, we chose an optimal addition scheme in
which TGF beta-2 was added in primary culture and first passage, followed by
addition of L-ascorbic acid in the second and third passage; this resulted in a 7
fold increase in cell number compared to the control group, in about 4 weeks. Our
findings stress the importance of adding the right growth factor at the right
moment. Collagen type II expression was lost after the third passage, in the
control as well as in the experimental condition. The ability to produce hyaline
cartilage specific matrix components is essential, if multiplied cells are to be
used to repair cartilage defects.
PMID- 10191752
TI - Alendronate did not inhibit instability-induced bone resorption. A study in rats.
AB - Alendronate is a bisphosphonate that can decrease osteoclastic activity. It has
been suggested as treatment for periprosthetic osteolysis. We used 48 rats, of
which 32 had a plate implant on one tibia, to study the effect of alendronate on
bone resorption at an unstable implant-bone interface. The plate has a handle on
top, which can be grasped through the skin and turned, to create a sliding motion
of a titanium surface against the underlying bone. This is known to result in
bone resorption, which was studied by histomorphometry. Osmotic minipumps were
used to administer alendronate at 0.063 mg/kg/day or saline. The systemic effect
of the treatment was assessed by ashing the proximal metaphyses of the tibia of
the contralateral unoperated leg. The ash-weight was increased in the alendronate
treated group by 43% (p = 0.0001), corresponding to histological changes in the
metaphyseal bone. There was no inhibition of the instability-induced bone
resorption at the test surface by alendronate: bone was being resorbed and
replaced by a tissue similar to a loosening membrane.
PMID- 10191753
TI - DXA-derived section modulus and bone mineral content predict long-bone torsional
strength.
AB - Previous studies have used dual energy x-ray absorptiometry (DXA) scans to
calculate the section modulus (Z) of adolescent and adult human femurs. The DXA
derived values of Z were assumed to be proportional to bone strength in bending
and torsion. In this study we used dog (n 5), pig (n 4), and human (n 13) femurs
covering a linear bone mineral content (BMCL) range of 0.91-6.1 g/cm. Using DXA
scans, ex vivo torsional strength tests, and torsional finite element models, we
assessed the validity of using the DXA-derived Z value as an indicator of
strength. The correlation between BMCL and strength was r2 = 0.87 and the
correlation between Z and strength was r2 = 0.86. Based on finite element
results, the dog and pig section moduli were adjusted to be comparable to the
human data based on cross-sectional shape and bone tissue shear strength
differences. With these adjustments, the correlation between adjusted section
modulus and measured strength did not improve (r2 = 0.87). These data indicate
that DXA-derived section modulus can be used to predict strength over a wide
range of bone sizes. However, a clear advantage of using DXA-derived section
modulus rather than BMCL could not be found.
PMID- 10191754
TI - Intraosseous BMP implants in rabbits. Inhibitory effect on bone formation.
AB - The bone harvest chamber is a model for rapid spontaneous bone healing in
rabbits. We have previously shown inhibition of bone formation by using BMP-2 on
a collagen carrier in this intraosseous model, despite bone formation when
depositing BMP-2 on a similar carrier subfascially in the same animals. The doses
were 12 and 0.6 micrograms/5 mm3 chamber volume. As these findings conflicted
with most other experiments dealing with the skeletal response to BMP-2, we
repeated the previous experiments with variations. We studied: 1) a lower BMP-2
dose, 2) a different type of BMP (BMP-7/OP-1), 3) a different carrier
(hydroxyapatite), 4) a different chamber construction allowing contact with
extraskeletal tissue and 5) BMP-2 on the original collagen carrier in an acutely
inserted chamber in rats. We also studied the border between the BMP-2 implant
and the preexisting bone to see whether BMP-2 caused premature differentiation of
the callus so that proliferation was stopped and a bone cyst formed. The low dose
of BMP-2 reduced tissue ingrowth and tended to reduce bone formation. BMP-7
showed the same inhibitory effects as BMP-2. BMP-2 on a hydroxyapatite carrier
also inhibited bone formation in the chamber. In the chamber that allowed contact
with extraskeletal tissue, we observed no effects of BMP-2. The border between
the BMP-2 implant and the preexisting bone did not look like a cyst wall. BMP-2,
from the same batch, on a similar collagen carrier, regularly increased bone
formation in the acutely inserted bone chamber in rats, thereby excluding major
defects in the BMP-2 implants. The inhibition in this specific model is a
consistent finding and not due to an overdose, a specific BMP-type, a specific
carrier or premature callus differentiation.
PMID- 10191755
TI - Scapular body stress fracture--a case report.
PMID- 10191756
TI - Extension restriction of the elbow caused by a synovial fold--a report on 2
athletes.
PMID- 10191757
TI - Insufficiency fracture of the femoral head in patients with severe osteoporosis-
report of 2 cases.
PMID- 10191758
TI - Late repair of rupture of the hamstring tendons from the ischial tuberosity--a
case report.
PMID- 10191759
TI - Bilateral atraumatic avulsion fracture of the calcaneal tubercle in osteomalacia
during fluoride therapy--a case report.
PMID- 10191760
TI - Ilizarov circular external fixator for open olecranon fractures--a report of 3
cases.
PMID- 10191761
TI - The crowded wrist--a case with accessory carpal bones.
PMID- 10191762
TI - RAB-plate vs Richards CHS plate for unstable trochanteric hip fractures--a
randomized study of 233 patients with 1-year follow-up.
PMID- 10191763
TI - FDA issues final rule for classification and reclassification of immunochemistry
reagents and kits.
PMID- 10191764
TI - Labels, disclaimers, and rules (oh, my!). Analyte-specific reagents and practice
of immunohistochemistry.
PMID- 10191765
TI - Association for Molecular Pathology statement. Recommendations for in-house
development and operation of molecular diagnostic tests.
PMID- 10191766
TI - Acute lymphoblastic leukemia. Survey of immunophenotype, French-American-British
classification, frequency of myeloid antigen expression, and karyotypic
abnormalities in 210 pediatric and adult cases.
AB - Immunophenotypic studies are essential to distinguish acute lymphoblastic
leukemia (ALL) from minimally differentiated acute myeloid leukemia (AMLM0) and
to classify ALL into immunologic subtypes. Frequently, immunophenotyping
identifies myeloid antigen expression in ALL, causing a potential diagnostic
problem. To evaluate the immunophenotype of ALL, we studied 210 cases of
pediatric and adult ALL by flow cytometry and compared the results with the
French-American-British (FAB) Cooperative Group classification and the karyotypic
findings. Myeloid-associated antigens were expressed in 78 (45.6%) of precursor B
cell ALL cases. Pediatric precursor B ALLs had a higher frequency of myeloid
antigen expression than did adult cases. All mature B-cell ALL cases were
negative for TdT and myeloid antigens. Myeloid antigen expression was less
frequent in T-cell ALL cases compared with precursor B-cell ALL cases. Of the 192
cases submitted for cytogenetic analysis, 147 were abnormal. The most common
chromosomal translocation was the Philadelphia chromosome, which was more likely
to have L2 blast morphology and a precursor B immunophenotype. Myeloid antigen
expression was present in 70.8% of Ph-positive cases (P = .008). Chromosome
rearrangements involving 11q23 also showed an increased frequency of myeloid
antigen expression. Chromosome translocations involving regions of T-cell
receptor genes were present in 24% of T-cell ALL cases. A high percentage of ALL
cases, however, had various other cytogenetic abnormalities, many of which
involved less well-studied chromosomal regions.
PMID- 10191767
TI - CD5- B-cell lymphoproliferative disorders presenting in blood and bone marrow. A
clinicopathologic study of 40 patients.
AB - We studied 40 patients with CD5- B-cell lymphoproliferative disorders (B-LPDs)
presenting in blood or bone marrow and 28 control patients with CD5+ B-cell
chronic lymphocytic leukemia (CLL). Fifteen study patients had morphologic
features typical of CLL. The 15 patients with CD5- CLL were older and had lower
absolute lymphocyte counts and more advanced-stage disease at diagnosis than
controls. Ten study patients had morphologic features suggesting mantle cell
lymphoma (MCL); 3 were later given a diagnosis of MCL based on lymph node biopsy
results. The 10 patients with CD5- MCL were older and at a more advanced stage
than CLL control patients. The remaining 15 study patients were given the
following diagnoses: circulating non-Hodgkin lymphoma, 5; splenic lymphoma with
villous lymphocytes, 5; lymphoplasmacytoid lymphoma, 3; and CLL/pro-lymphocytic
leukemia, 2. For the patients with CD5- B-LPDs with morphologic features and
manifestations resembling CLL, we prefer the term CD5- CLL variant because of
clinical and immunophenotypic differences. Patients with CD5- B-LPDs with
atypical nuclear morphologic features may represent the leukemic phase of MCL.
Since CD23 is expressed in most patients with CD5- B-LPD, its use in
subclassifying these disorders seems limited.
PMID- 10191768
TI - Frequency of CD43 expression in non-Hodgkin lymphoma. A survey of 742 cases and
further characterization of rare CD43+ follicular lymphomas.
AB - CD43 expression on B cells is an immunophenotypic feature suggestive of
malignancy. In the light of its diagnostic importance, we performed a
comprehensive survey of CD43 expression in various types of non-Hodgkin lymphoma
(NHL) and determined the frequency of its expression in routinely fixed paraffin
embedded tissues. Tissue sections in 742 cases of NHL, pretreated by the heat
induced epitope retrieval technique, were immunostained using an anti-CD43
antibody. Three categories of CD43 positivity were found: (1) more than 90% of T
cell lymphoma, mantle cell lymphoma, B-cell small lymphocytic lymphoma, and
Burkitt lymphoma cases were positive; (2) 20% to 40% of nodal and extranodal
marginal zone lymphoma (MZL), diffuse large B-cell lymphoma, Burkitt-like B-cell
lymphoma, and lymphoplasmacytoid lymphoma cases were positive; and (3) 0% to 6%
of primary splenic MZL and various types of follicular lymphoma cases were
positive. Most CD43+ follicular lymphomas were predominantly large cell type with
focally diffuse areas; their follicular center cell origin in 4 of 8 cases was
supported by the presence of CD10 immunoreactivity and/or t(14;18) fusion gene
product. CD43 is frequently detectable in a subset of B-NHL, and, thus, it seems
to be a highly sensitive marker for these tumors. CD43 also may be a useful
marker for classifying B-cell NHLs by virtue of its differential expression in
these tumors.
PMID- 10191769
TI - Leukemic phase of mantle cell lymphoma, blastoid variant.
AB - Six patients with mantle cell lymphoma, blastoid variant, involving the blood are
described. The circulating blast-like cells suggested the possibility of acute
leukemias, chronic lymphoproliferative disorders or peripheralized lymphomas. The
WBC counts ranged from 3,700 to 249,000/microL (3.7-249.0 x 10(9)/L) and the
absolute lymphocyte counts from 1,000 to more than 200,000/microL (1.0 to > 200.0
x 10(9)/L). The peripheral blood smears showed a spectrum of cells, from small
mature lymphocytes with irregular nuclei to medium-sized lymphocytes with blast
like chromatin. However, the morphologic features in a lymph node biopsy specimen
and the immunophenotype confirmed a diagnosis of mantle cell lymphoma, blastoid
variant. By flow cytometry the lymphoma cells expressed B-cell-associated
antigens (CD19, CD20 and CD22), coexpressed CD5, lacked CD23, and expressed
moderate intensity monoclonal surface immunoglobulin and CD20. Cytogenetic
analysis showed the characteristic t(11;14) in 2 of 4 analyzed specimens. Mantle
cell lymphoma, blastoid variant, is part of the differential diagnosis for blast
like cells.
PMID- 10191770
TI - Comparison of an enzyme immunoassay to an indirect fluorescent immunoassay for
the detection of antinuclear antibodies.
AB - The standard method for detecting antinuclear antibodies (ANAs) is by
immunofluorescence assay (IFA), a method that is labor intensive and subjective.
In an attempt to overcome these limitations, several commercial enzyme
immunoassays (EIAs) have been developed. We report the results of our evaluation
of the ANA Microplate EIA (Sanofi Diagnostics Pasteur, Chaska, MN). For the
evaluation, 808 serum samples were tested by EIA and IFA; 52 specimens were
positive by both assays, 561 were negative by both assays, 91 were positive by
EIA only, and 3 were positive by IFA only. Borderline results (not positive or
negative) were obtained for 101 specimens, which were excluded when calculating
the sensitivity, specificity, and positive and negative predictive values of this
assay, which were 94.6%, 86.0%, 36.4%, and 99.5%, respectively. Because of its
high negative predictive value, this assay can be used reliably to detect ANA
negative samples; however, the low positive predictive value indicates that EIA
positive specimens should be retested by an IFA to determine the final result.
PMID- 10191771
TI - International Consensus Statement on Testing and Reporting of Antineutrophil
Cytoplasmic Antibodies (ANCA)
AB - Antineutrophil cytoplasmic antibody (ANCA) tests are used to diagnose and monitor
inflammatory activity in the primary systemic small vessel vasculitides. ANCA is
best demonstrated in these diseases by using a combination of indirect
immunofluorescence (IIF) of normal peripheral blood neutrophils and enzyme-linked
immunosorbent assays (ELISAs) that detect ANCA specific for proteinase 3 (PR3) or
myeloperoxidase (MPO). For ANCA testing in "new" patients, IIF must be performed
on all serum samples. Serum samples containing ANCA, any other cytoplasmic
fluorescence, or an antinuclear antibody (ANA) that results in homogeneous or
peripheral nuclear fluorescence then should be tested in ELISAs for PR3-ANCA and
MPO-ANCA. Optimally, ELISAs for PR3-ANCA and MPO-ANCA should be performed on all
serum samples. Inclusion of the most recent positive sample in the IIF or ELISA
may help demonstrate a change in antibody level. Reports should use recommended
terms. Any report of positive neutrophil fluorescence issued before the ELISA
results are available should indicate that positive fluorescence alone is not
specific for the diagnosis of Wegener granulomatosis or microscopic polyangiitis
and that decisions about treatment should not be based solely on the ANCA
results.
PMID- 10191772
TI - Performance characteristics of rapid (30-second) prescreening. Implications for
calculating the false-negative rate and comparison with other quality assurance
techniques.
AB - Rapid (30-second) prescreening of cervicovaginal smears can be used to detect
false-negative cases and determine the false-negative rate of primary screening,
but the performance characteristics have not been evaluated fully. A test set of
242 cases including 80 originally false-negative cases were rapidly screened by 4
different cytotechnologists on 2 occasions. Intraobserver and interobserver
reproducibility were good. Median specificity for each round of observations was
89% (range, 30%-96%). Median sensitivity for all true-positive cases was 78%
(range, 63%-97%); for all false-negative cases it was 59% (range, 38%-89%). The
relative sensitivity of rapid screening for true-positive and false-negative
cases varied with the diagnosis. Rapid screening detected almost the same
percentage of false-negative cases of atypical squamous cells of uncertain
significance (ASCUS) as true-positive ASCUS cases (median ratio, 1.12; range,
0.72-1.52). The median ratio of false-negative to true-positive ASCUS cases was
significantly different than the ratio for low-grade plus high-grade squamous
intraepithelial lesions (0.68; range, 0.50-0.96). Although performance varies
between individuals, in this test population the reproducibility, specificity,
and sensitivity were good. Because it detects more false-negative cases at a
lower cost per case than routine rescreening, rapid prescreening should be
considered as an alternative to current quality control measures.
PMID- 10191773
TI - Breast fine-needle aspiration. A comparison of ThinPrep and conventional smears.
AB - Fine-needle aspiration (FNA) of the breast has been used in our institution since
1969. In August 1993, ThinPrep (Cytyc Corp, Boxbotough, MA) processing of breast
FNA biopsy specimens was introduced. Comparing conventionally prepared breast FNA
specimens (21,193 cases) with ThinPrep processed material (7,903 cases) shows a
decrease in the unsatisfactory rate with the ThinPrep processing (29.5% to 27.7%)
with no significant change in sensitivity (84.4% vs 86.3%) or positive predictive
value (96.5 vs 95.0%). However, there is a slight decrease in specificity (98.6%
vs 96.5%) and negative predictive value (91.1% vs 88.0%) with the ThinPrep
specimens. The results span 28 years, during which time the breast cancer
population has changed, with a higher prevalence of malignancy in the last decade
of our study. When the 4 most recent years of conventional cytology are compared
with the 4 years of ThinPrep processing, there is no significant difference in
diagnostic accuracy. The results of the present study show that the ThinPrep
processing technique provides an effective method for preparing breast FNA.
specimens.
PMID- 10191774
TI - Detection of SYT-SSX fusion transcript in synovial sarcoma using archival
cytologic specimens.
AB - Identification of the SYT-SSX fusion transcript can be a useful diagnostic aid
for synovial sarcoma. However, there is no report on the detection of the
specific transcript in archival cytologic specimens. We performed a rapid reverse
transcription-polymerase chain reaction assay to detect the fusion transcript
using such specimens as RNA sources and compared its usefulness with the assay
using formalin-fixed paraffin-embedded histologic specimens. Eleven cytologic and
12 histologic specimens stored for 0.1 to 20 years were selected from 9 patients.
The SYT-SSX transcript was identified in 10 (91%) of 11 of cytologic and 9 (75%)
of 12 histologic cases. One of the transcript-positive cytologic cases was
obtained by fine-needle aspiration. SYT-SSX1 fusion was found in 4 patients and
SYT-SSX2 in 5. Cytologic specimens will be an excellent RNA source for the
reverse transcription-polymerase chain reaction diagnosis of synovial sarcoma
with a sensitivity of more than 90%, comparable to that in frozen materials.
Histologic materials also may be useful when cytologic or frozen materials are
not available.
PMID- 10191775
TI - Extratesticular extension of germ cell tumors preferentially occurs at the hilum.
AB - Germ cell tumors that extend beyond the testis are associated with a higher risk
of metastasis. However, it is not known whether extratesticular invasion occurs
at a preferential site. We reviewed all primary testicular germ cell tumors
resected at the Brigham and Women's Hospital, Boston, MA, between July 1, 1987,
and July 31, 1997. Of 142 total cases, 23 (16.2%) cases showed extratesticular
extension. Thirty additional cases (21.1%), which had lymphatic or vascular
invasion only, without interstitial involvement of extratesticular structures,
were excluded. Extratesticular extension most likely occurred only at the hilum
in 21 (91%) cases; 2 additional cases (9.5%) with tumor in the epididymis did not
contain sections of hilum; however, the tunica albuginea was well sampled in
these cases, and no separate site of tunica invasion was found. Multiple sections
of the tunica albuginea were present in all cases, and penetration of the tunica
albuginea was not identified in any case. Extratesticular extension was
identified on gross examination of the orchiectomy specimen in only 8 of 18 (44%)
cases. Extratesticular extension of germ cell tumors preferentially occurs at the
hilum, and frequently the extension at this site is grossly inapparent.
Histologic examination of the hilum should be performed in all cases of
testicular germ cell tumors.
PMID- 10191776
TI - Subtypes of renal cell carcinoma. Different onset and sites of metastatic
disease.
AB - Different subtypes of renal cell carcinoma have different genetic features and
prognoses. Whether the patterns of metastatic spread of different subtypes of
renal cell carcinoma are different is unknown. To assess this, we reviewed the
time course and sites of all pathologically confirmed metastatic disease in
patients who underwent resection of the primary tumor at Brigham and Women's
Hospital, Boston, MA, between 1973 and 1997. In 82 patients, 119 metastatic
lesions were identified. Compared with clear cell tumors, papillary tumors were
more likely to be Fuhrman grade 3 or 4, to have metastases present at the time of
resection, and to involve lymph nodes but not lung. Metastases associated with
chromophobe tumors developed in 3 patients, all of whom had Fuhrman grade 2
tumors, and were found only in the liver. We conclude that different subtypes of
renal cell carcinoma develop pathologically confirmed metastases at different
times and sites. The value of Fuhrman grading may depend on the subtype of renal
cell carcinoma.
PMID- 10191777
TI - Technical evaluation of five glucose meters with data management capabilities.
AB - Technical performance and data management features are prominent criteria in the
selection of an appropriate meter for a point-of-care glucose testing program. We
evaluated the technical performance of 5 currently available glucose meters with
data management capabilities. The performance of all 5 meters was technically
equivalent. Linear regression slopes vs the reference method are in the range of
0.94 to 1.02 and indicate correlation more to plasma values than to whole blood
values. The percentage of glucose meter results within +/- 15% of the laboratory
value was at least 90%; however, the percentage within +/- 10% was 75% to 87% for
most meters. Within-day and between-day precision ranged from 2% to 5%
coefficient of variation. Evaluation of linearity with glucose-spiked venous
specimens demonstrated that the linearity of each meter agreed with the
manufacturer's stated range in most cases. Meter glucose values tended to bias
negative as the hematocrit increased, an effect that may be more pronounced at
higher glucose concentrations. No volume effects were noted between 5 microL and
40 microL. The results suggest that all meters tested will likely satisfy
technical performance criteria in a hospital setting and that selection of a
system for point-of-care glucose testing will be influenced by the institution's
data management requirements.
PMID- 10191778
TI - Use of alkaline phosphatase to correct the underestimation of fosphenytoin
concentration in serum measured by phenytoin immunoassays.
AB - The pharmacologic activity of fosphenytoin, a new phosphate ester pro-drug of
phenytoin, is due to in vivo conversion to phenytoin. Fosphenytoin concentrations
cannot be accurately estimated by phenytoin immunoassays (fluorescence
polarization and chemiluminescence) owing to the nonlinear relation between
fosphenytoin concentration and the observed cross-reactivity. The problem of slow
conversion of fosphenytoin to phenytoin in serum in vitro can be circumvented by
rapidly converting fosphenytoin to phenytoin in vitro by alkaline phosphatase.
Drug-free serum, heparin, EDTA, or citrated plasma were supplemented with 2
concentrations of fosphenytoin. Then to 1-mL aliquots of specimen, no enzyme
(control), 10 microL, or 25 microL of enzyme solution was added. The specimens
were incubated, and phenytoin concentrations were measured by fluorescence
polarization and chemiluminescent assays. In the absence of enzyme, we observed
little conversion of fosphenytoin to phenytoin, but in the presence of only 10
microL of enzyme, the conversion of fosphenytoin to phenytoin was complete in 5
minutes. We also observed complete conversion of fosphenytoin to phenytoin by
alkaline phosphatase in heparin, EDTA, and citrated plasma. If clinically
indicated, the phenytoin concentration can be measured before and after addition
of enzyme to roughly estimate the rate of conversion.
PMID- 10191779
TI - Thromboplastins, heparin, and polybrene.
PMID- 10191780
TI - The risks of heparin-neutralizing substances.
PMID- 10191781
TI - Estimating interobserver reliability.
PMID- 10191782
TI - Plasmacytoid monocytes?
PMID- 10191783
TI - What's a mother to do? Welfare, work, and family.
PMID- 10191784
TI - The Safe Motherhood Initiative: why has it stalled?
AB - Complications of pregnancy and childbirth are still the leading cause of death
and disability among women of reproductive age in developing countries. After
decades of neglect, the founding of the Safe Motherhood Initiative in 1987
promised action on this problem. A dozen years later, there is no evidence that
maternal mortality has declined and there are still few sizeable programs. A
major reason for this disappointing record is that the initiative lacks a clear,
concise, feasible strategy. This article reviews the available options and
proposes a strategy based on improving the availability and quality of medical
treatment of obstetric complications. Once district hospitals and health centers
provide such needed care, community mobilization to improve prove utilization may
be beneficial. Substantial reductions in maternal deaths would be possible in a
relatively short period of time if this strategy were embraced.
PMID- 10191785
TI - Science, justice, and breast implants.
PMID- 10191786
TI - Silicone breast implants: epidemiological evidence of sequelae.
AB - Skeptics may certainly find fault with the third study (the only one to report a
significant finding) or with all or any of the statistics described. But few
could argue, after examining these studies, that the relative risk for a known
and well-defined connective tissue disease is likely greater than 2. Another
possibility has been raised, one that calls to mind other difficult-to-study
syndromes linked to exposures. In a study addressing Gulf War syndrome, signs and
symptoms were often mentioned that proved difficult to describe systematically
and therefore difficult to study. What if a suspected silicone exposure syndrome
were so mild and transient that it did not warrant a physician visit (as in the
Mayo Clinic study). receive a diagnosis (as in the Nurses' Health Study), or
require admission to a hospital (as in the Danish and Swedish studies)? And if
such a disorder were, in fact, mild and transient, should it merit the concern
that has been shown and the compensation that has been awarded in the silicone
implant litigation cases to date? We suggest that neither a well-described
disorder with a relative risk of less than 2 nor a transient and mild disorder
seems compatible with the number of litigants over silicone implants and the
apparent seriousness of their complaints. Some 400,000 women joined in one class
action suit for damages, and 170,000 joined in another. Even if there had been 2
million implants undertaken in the United States over the 3 decades in which
implant surgery has been practiced (and some estimates put the number closer to 1
million), there is no conceivable way in which a relative risk of 2 or 3 (or even
4) for each of the rare syndromes reported could explain so many exposed women
being affected. At most, 2200 out of 2 million unexposed women would be expected
to have had any one of the listed forms of connective tissue disorders, most of
which are very rare. Doubling the risk among the exposed population yields 4400,
and increasing the risk 20-fold produces 44,000. At this rate, there is no way in
which 400,000 litigants could all be affected. Extensions of the already
completed studies are ongoing, at least 1 of which is government funded;
apparently it is thought in the United States (though not in the United Kingdom
or elsewhere) that there is still room for reasonable doubt as to the supposed
causal relationships. But if epidemiology is invoked in the interest of public
health to prevent the many uses of silicone, the weight of the evidence
abstracted here supports the inference that silicone breast implants have not
been proved guilty of causing connective tissue disorders.
PMID- 10191787
TI - Ethics, epidemiology, and law: the case of silicone breast implants.
PMID- 10191788
TI - Burden of proof: judging science and protecting public health in (and out of) the
courtroom.
PMID- 10191789
TI - Comment: epidemiology and the new political economy of medicine.
PMID- 10191790
TI - The effect of a Medicaid managed care program on the adequacy of prenatal care
utilization in Rhode Island.
AB - OBJECTIVES: The purpose of this study was to determine whether adequacy of
prenatal care utilization improved after the implementation of a Medicaid managed
care program in Rhode Island. METHODS: Rhode Island birth certificate data (1993
1995; n = 37021) were used to analyze pre- and post-program implementation
changes in adequacy of prenatal care utilization. Logistic regression models were
used to characterize the variation in prenatal care adequacy as a function of
both time and the various covariates. RESULTS: Adequacy of prenatal care
utilization for Medicaid patients improved significantly after implementation of
the program, from 57.1% to 62.1% (odds ratio [OR] = 1.2, 95% confidence interval
[CI] = 1.1, 1.3). After the program was implemented, Medicaid patients who went
to private physicians' offices for prenatal care were 1.4 times as likely as
before to receive adequate prenatal care (OR = 1.4, 95% CI = 1.2, 1.7).
CONCLUSIONS: Unlike many other Medicaid expansions for pregnant women, the RIte
Care program in Rhode Island has resulted in significant improvement in adequacy
of prenatal care utilization for its enrollees. This improvement was due to
specific program interventions that addressed and changed organizational and
delivery system barriers to care.
PMID- 10191791
TI - The impact of welfare reform on parents' ability to care for their children's
health.
AB - OBJECTIVES: Most of the national policy debate regarding welfare assumed that if
middle-income mothers could balance work while caring for their children's health
and development, mothers leaving welfare for work should be able to do so as
well. Yet, previous research has not examined the conditions faced by mothers
leaving welfare for work. METHODS: Using data from the National Longitudinal
Survey of Youth, this study examined the availability of benefits that working
parents commonly use to meet the health and developmental needs of their
children; paid sick leave, vacation leave, and flexible hours. RESULTS: In
comparison with mothers who had never received welfare, mothers who had been on
Aid to Families with Dependent Children were more likely to be caring for at
least 1 child with a chronic condition (37% vs 21%, respectively). Yet, they were
more likely to lack sick leave for the entire time they worked (36% vs 20%) and
less likely to receive other paid leave or flexibility. CONCLUSIONS: If current
welfare recipients face similar conditions when they return to work, many will
face working conditions that make it difficult or impossible to succeed in the
labor force at the same time as meeting their children's health and developmental
needs.
PMID- 10191792
TI - Maternal intrapartum temperature elevation as a risk factor for cesarean delivery
and assisted vaginal delivery.
AB - OBJECTIVES: This study investigated the association of intrapartum temperature
elevation with cesarean delivery and assisted vaginal delivery. METHODS:
Participants were 1233 nulliparous women with singleton, term pregnancies in
vertex presentations who had spontaneous labors and were afebrile (temperature:
99.5 degrees F [37.5 degrees C]) at admission for delivery. Rates of cesarean and
assisted vaginal deliveries according to highest intrapartum temperature were
examined by epidural status. RESULTS: Women with maximum intrapartum temperatures
higher than 99.5 degrees F were 3 times as likely to experience cesarean (25.2%
vs 7.2%) or assisted vaginal delivery (25.2% vs 8.5%). The association was
present in epidural users and nonusers and persisted after birthweight, epidural
use, and labor length had been controlled. In adjusted analyses, temperature
elevation was associated with a doubling in the risk of cesarean delivery (odds
ratio [OR] = 2.3, 95% confidence interval [CI] = 1.5, 3.4) and assisted vaginal
delivery (OR = 2.1, 95% CI = 1.4, 3.1). CONCLUSIONS: Modest temperature elevation
developing during labor was associated with higher rates of cesarean and assisted
vaginal deliveries. More frequent temperature elevation among women with epidural
analgesia may explain in part the higher rates of cesarean and assisted vaginal
deliveries observed with epidural use.
PMID- 10191793
TI - Perinatal risk and severity of illness in newborns at 6 neonatal intensive care
units.
AB - OBJECTIVES: This multisite study sought to identify (1) any differences in
admission risk (defined by gestational age and illness severity) among neonatal
intensive care units (NICUs) and (2) obstetric antecedents of newborn illness
severity. METHODS: Data on 1476 babies born at a gestational age of less than 32
weeks in 6 perinatal centers were abstracted prospectively. Newborn illness
severity was measured with the Score for Neonatal Acute Physiology. Regression
models were constructed to predict scores as a function of perinatal risk
factors. RESULTS: The sites differed by several obstetric case-mix
characteristics. Of these, only gestational age, small for gestational age. White
race, and severe congenital anomalies were associated with higher scores.
Antenatal corticosteroids, low Apgar scores, and neonatal hypothermia also
affected illness severity. At 2 sites, higher mean severity could not be
explained by case mix. CONCLUSIONS: Obstetric events and perinatal practices
affect newborn illness severity. These risk factors differ among perinatal
centers and are associated with elevated illness severity at some sites. Outcomes
of NICU care may be affected by antecedent events and perinatal practices.
PMID- 10191794
TI - Consanguinity and recurrence risk of stillbirth and infant death.
AB - OBJECTIVES: The aim of this study was to estimate the recurrence risk for
stillbirth and infant death and compare results for offspring of first-cousin
parents with results for offspring of unrelated parents. METHODS: The study
population consisted of all single births with a previous sibling born in Norway
between 1967 and 1994. Altogether, 629,888 births were to unrelated parents, and
3466 births were to parents who were first cousins. The risk of stillbirth and
infant death was estimated for subsequent siblings contingent on parental
consanguinity and survival of the previous sibling. RESULTS: For unrelated
parents, the risk of early death (stillbirth plus infant death) for the
subsequent sibling was 17 of 1000 if the previous child survived and 67 of 1000
if the previous child died before 1 year of age. For parents who were first
cousins, the risk of early death for the subsequent sibling was 29 of 1000 if the
previous child survived and 116 of 1000 if the previous child died. CONCLUSIONS:
The risk of recurrence of stillbirth and infant death is higher for offspring of
first-cousin parents compared with offspring of unrelated parents.
PMID- 10191795
TI - Improving access to disability benefits among homeless persons with mental
illness: an agency-specific approach to services integration.
AB - OBJECTIVES: This study evaluated a joint initiative of the Social Security
Administration (SSA) and the Department of Veterans Affairs (VA) to improve
access to Social Security disability benefits among homeless veterans with mental
illness. METHODS: Social Security personnel were colocated with VA clinical staff
at 4 of the VA's Health Care for Homeless Veterans (HCHV) programs. Intake
assessment data were merged with SSA administrative data to determine the
proportion of veterans who filed applications and who received disability awards
at the 4 SSA-VA Joint Outreach Initiative sites (n = 6709) and at 34 comparison
HCHV sites (n = 27 722) during the 2 years before and after implementation of the
program. RESULTS: During the 2 years after the initiative began, higher
proportions of veterans applied for disability (18.9% vs 11.1%; P < .001) and
were awarded benefits (11.4% vs 7.2%, P < .001) at SSA-VA Joint Initiative sites.
CONCLUSION: A colocation approach to service system integration can improve
access to disability entitlements among homeless persons with mental illness.
Almost twice as many veterans were eligible for this entitlement as received it
through a standard outreach program.
PMID- 10191796
TI - Mortality among homeless shelter residents in New York City.
AB - OBJECTIVES: This study examined the rates and predictors of mortality among
sheltered homeless men and women in New York City. METHODS: Identifying data on a
representative sample of shelter residents surveyed in 1987 were matched against
national mortality records for 1987 through 1994. Standardized mortality ratios
were computed to compare death rates among homeless people with those of the
general US and New York City populations. Logistic regression analysis was used
to examine predictors of mortality within the homeless sample. RESULTS: Age
adjusted death rates of homeless men and women were 4 times those of the general
US population and 2 to 3 times those of the general population of New York City.
Among homeless men, prior use of injectable drugs, incarceration, and chronic
homelessness increased the likelihood of death. CONCLUSIONS: For homeless shelter
users, chronic homelessness itself compounds the high risk of death associated
with disease/disability and intravenous drug use. Interventions must address not
only the health conditions of the homeless but also the societal conditions that
perpetuate homelessness.
PMID- 10191797
TI - Explaining educational differences in mortality: the role of behavioral and
material factors.
AB - OBJECTIVES: This study examined the role of behavioral and material factors in
explaining educational differences in all-cause mortality, taking into account
the overlap between both types of factors. METHODS: Prospective data were used on
15,451 participants in a Dutch longitudinal study. Relative hazards of all-cause
mortality by educational level were calculated before and after adjustment for
behavioral factors (alcohol intake, smoking, body mass index, physical activity,
dietary habits) and material factors (financial problems, neighborhood
conditions, housing conditions, crowding, employment status, a proxy of income).
RESULTS: Mortality was higher in lower educational groups. Four behavioral
factors (alcohol, smoking, body mass index, physical activity) and 3 material
factors (financial problems, employment status, income proxy) explained part of
the educational differences in mortality. With the overlap between both types of
factors accounted for, material factors were more important than behavioral
factors in explaining mortality differences by educational level. CONCLUSIONS:
The association between educational level and mortality can be largely explained
by material factors. Thus, improving the material situation of people might
substantially reduce educational differences in mortality.
PMID- 10191798
TI - Factors associated with refusal to treat HIV-infected patients: the results of a
national survey of dentists in Canada.
AB - OBJECTIVES: This study investigated dentists refusal to treat patients who have
HIV. METHODS: A survey was mailed to a random sample of all licensed dentists in
Canada, with 3 follow-up attempts (n = 6444). Data were weighted to allow for
probability of selection and nonresponse and analyzed with Pearson's chi 2 and
multiple logistic regression. RESULTS: The response rate was 66%. Of the
respondents, 32% had knowingly treated HIV-infected patients in the last year;
16% would refuse to treat HIV-infected patients. Respondents reported willingness
to treat HIV-infected patients (81%), injection drug users (86%), hepatitis B
virus-infected patients (87%), homosexual and bisexual persons (94%), individuals
with sexually transmitted disease(s) (94%), and recipients of blood and blood
products (97%). The best predictors of refusal to treat patients with HIV were
lack of ethical responsibility (odds ratio = 9.0) and items related to fear of
cross-infection or lack of knowledge of HIV. CONCLUSIONS: One in 6 dentists
reported refusal to treat HIV-infected patients, which was associated primarily
with respondents' lack of belief in an ethical responsibility to treat patients
with HIV and fears related to cross-infection. These results have implications
for undergraduate, postgraduate, and continuing education.
PMID- 10191799
TI - The prevalence and health burden of self-reported diabetes in older Mexican
Americans: findings from the Hispanic established populations for epidemiologic
studies of the elderly.
AB - OBJECTIVES: The prevalence and health burden of self-reported adult-onset
diabetes mellitus were examined in older Mexican Americans. METHODS: Data from
the Hispanic Established Populations for Epidemiologic Studies of the Elderly
were used to assess the prevalence of self-reported diabetes and its association
with other chronic conditions, disability, sensory impairments, health behaviors,
and health service use in 3050 community-dwelling Mexican Americans 65 years and
older. RESULTS: The prevalence of self-reported diabetes in this sample was 22%,
and there were high rates of obesity, diabetes-related complications, and
diabetic medication use. Myocardial infarction, stroke, hypertension, angina, and
cancer were significantly more common in diabetics than in nondiabetics, as were
high levels of depressive symptoms, low perceived health status, disability,
incontinence, vision impairment, and health service use. Many of the rate
differences found in this sample of older Mexican Americans were higher than
those reported among other groups of older adults. CONCLUSIONS: Our findings
indicate that the prevalence and health burden of diabetes are greater in older
Mexican Americans than in older non-Hispanic Whites and African Americans,
particularly among elderly men.
PMID- 10191800
TI - A population-based study of environmental hazards in the homes of older persons.
AB - OBJECTIVES: This study sought to estimate the population-based prevalence of
environmental hazards in the homes of older persons and to determine whether the
prevalence of these hazards differs by housing type or by level of disability in
terms of activities of daily living (ADLs). METHODS: An environmental assessment
was completed in the homes of 1000 persons 72 years and older. Weighted
prevalence rates were calculated for each of the potential hazards and
subsequently compared among subgroups of participants characterized by housing
type and level of ADL disability. RESULTS: Overall, the prevalence of most
environmental hazards was high. Two or more hazards were found in 59% of
bathrooms and in 23% to 42% of the other rooms. Nearly all homes had at least 2
potential hazards. Although age-restricted housing was less hazardous than
community housing, older persons who were disabled were no less likely to be
exposed to environmental hazards than older persons who were nondisabled.
CONCLUSIONS: Environmental hazards are common in the homes of community-living
older persons.
PMID- 10191801
TI - An epidemic of congenital syphilis in Jefferson County, Texas, 1994-1995:
inadequate prenatal syphilis testing after an outbreak in adults.
AB - OBJECTIVES: After a syphilis epidemic in Jefferson County, Texas, in 1993 and
1994, congenital syphilis prevalence and risk factors were determined and local
prenatal syphilis screening practices were assessed. METHODS: Medical records
were reviewed, pregnant women with syphilis were interviewed, and prenatal care
providers were surveyed. RESULTS: Of 91 women, 59 (65%) had infants with
congenital syphilis. Among African Americans, the prevalence per 1000 live births
was 24.1 in 1994 and 17.9 in 1995. Of the 50 women with at least 2 prenatal care
visits who had infants with congenital syphilis, 15 (30%) had received inadequate
testing. Only 16% of 31 providers obtained an early third-trimester syphilis test
on all patients. CONCLUSIONS: Inadequate prenatal testing contributed to this
outbreak of congenital syphilis.
PMID- 10191802
TI - The effects on fetal development of high alpha-fetoprotein and maternal smoking.
AB - OBJECTIVES: This study determined the risk of impaired fetal growth resulting
from the interaction between maternal smoking during pregnancy and unexplained
elevated concentrations of maternal serum alpha-fetoprotein (MSAFP). METHODS:
This observational study involved 123 pregnant smokers with unexplained second
trimester elevated concentrations of MSAFP, 827 smokers with normal levels, and
471 nonsmokers with raised levels. RESULTS: By logistic regression, coincident
smoking and elevated MSAFP levels were found to be associated with increases in
the low basic risks of prematurity, small-for-gestational-age births, low
birthweight, and need for neonatal care. CONCLUSIONS: Maternal smoking has an
adverse effect on fetal development in pregnancies with unexplained elevated
MSAFP concentrations. Such pregnancies merit close surveillance.
PMID- 10191803
TI - Method of linking Medicaid records to birth certificates may affect infant
outcome statistics.
AB - OBJECTIVES: This study assessed how different methods of matching Medicaid
records to birth certificates affect Medicaid infant outcome statistics. METHODS:
Claims paid by Medicaid for hospitalization of the newborn and for the mother's
delivery were matched separately to 1995 North Carolina live birth certificates.
RESULTS: Infant mortality and low-birthweight rates were consistently lower when
Medicaid was defined by a matching newborn hospitalization record than when
results were based on a matching Medicaid delivery record. CONCLUSIONS: Studies
of birth outcomes in the Medicaid population may have variable results depending
on the method of matching that is used to identify Medicaid births.
PMID- 10191804
TI - Cost as a barrier to condom use: the evidence for condom subsidies in the United
States.
AB - OBJECTIVES: This study sought to determine the impact of price on condom use.
METHODS: A program based on distribution of condoms at no charge was replaced
with one providing low-cost condoms (25 cents). Pretest and posttest surveys
asked about condom use among persons reporting 2 or more sex partners. RESULTS:
At pretest, 57% of respondents had obtained free condoms, and 77% had used a
condom during their most recent sexual encounter. When the price was raised to 25
cents, the respective percentages decreased to 30% and 64%. CONCLUSIONS: Cost is
a barrier to condom use. Free condoms should be distributed to encourage their
use by persons at risk for HIV and other sexually transmitted diseases.
PMID- 10191805
TI - Socioeconomic status and morbidity in the last years of life.
AB - OBJECTIVES: This study evaluated the effect of socioeconomic status, as
characterized by level of education, on morbidity and disability in the last
years of life. METHODS: The analysis used data from the National Health Interview
Survey (1986-1990), with mortality follow-up through December 1991. RESULTS:
Among 10,932 decedents 50 years or older at baseline interview, educational
attainment was inversely associated with long-term limitation of activity, number
of chronic conditions, number of bed days, and days of short hospital stay during
the year preceding the interview. CONCLUSIONS: Decedents with higher
socioeconomic status experienced lower morbidity and disability and better
quality of life even in their last years of life.
PMID- 10191806
TI - Ischemic stroke risk and passive exposure to spouses' cigarette smoking.
Melbourne Stroke Risk Factor Study (MERFS) Group.
AB - OBJECTIVES: This study investigated the association between ischemic stroke risk
and passive exposure to cigarette smoking. METHODS: Risk factors among 452
hospitalized cases of first-episode ischemic stroke were compared with 452 age-
and sex-matched "neighbor-hood" controls. RESULTS: The risk of stroke was twice
as high for subjects whose spouses smoked as for those whose spouses did not
smoke (95% confidence interval = 1.3, 3.1), after adjustment for the subject's
own smoking, heart disease, hypertension, diabetes, and education level. These
results were confirmed when analysis was limited to those who never smoked.
CONCLUSIONS: These findings provide evidence that spousal smoking may be a
significant risk factor for ischemic stroke.
PMID- 10191807
TI - Mandatory reporting of intimate partner violence to police: views of physicians
in California.
AB - OBJECTIVES: This study examined physicians' perspectives on mandatory reporting
of intimate partner violence to police. METHODS: We surveyed a stratified random
sample of California physicians practicing emergency, family, and internal
medicine and obstetrics/gynecology. RESULTS: An estimated 59% of California
primary care and emergency physicians (n = 508, 71% response rate) reported that
they might not comply with the reporting law if a patient objects. Primary care
physicians reported lower compliance. Most physicians agreed that the legislation
has potential risks, raises ethical concerns, and may provide benefits.
CONCLUSIONS: Physicians' stated noncompliance and perceived negative consequences
raise the possibility that California's mandatory reporting law is problematic
and ineffective.
PMID- 10191808
TI - International developments in abortion law from 1988 to 1998.
AB - OBJECTIVES: In 2 successive decades since 1967, legal accommodation of abortion
has grown in many countries. The objective of this study was to assess whether
liberalizing trends have been maintained in the last decade and whether increased
protection of women's human rights has influenced legal reform. METHODS: A
worldwide review was conducted of legislation and judicial rulings affecting
abortion, and legal reforms were measured against governmental commitments made
under international human rights treaties and at United Nations conferences.
RESULTS: Since 1987, 26 jurisdictions have extended grounds for lawful abortion,
and 4 countries have restricted grounds. Additional limits on access to legal
abortion services include restrictions on funding of services, mandatory
counseling and reflection delay requirements, third-party authorizations, and
blockades of abortion clinics. CONCLUSIONS: Progressive liberalization has moved
abortion laws from a focus on punishment toward concern with women's health and
welfare and with their human rights. However, widespread maternal mortality and
morbidity show that reform must be accompanied by accessible abortion services
and improved contraceptive care and information.
PMID- 10191809
TI - Driving through: postpartum care during World War II.
AB - In 1996, public outcry over shortened hospital stays for new mothers and their
infants led to the passage of a federal law banning "drive-through deliveries."
This recent round of brief postpartum stays is not unprecedented. During World
War II, a baby boom overwhelmed maternity facilities in American hospitals.
Hospital births became more popular and accessible as the Emergency Maternal and
Infant Care program subsidized obstetric care for servicemen's wives. Although
protocols before the war had called for prolonged bed rest in the puerperium,
medical theory was quickly revised as crowded hospitals were forced to discharge
mothers after 24 hours. To compensate for short inpatient stays, community-based
services such as visiting nursing care, postnatal homes, and prenatal classes
evolved to support new mothers. Fueled by rhetoric that identified maternal-child
health as a critical factor in military morale, postpartum care during the war
years remained comprehensive despite short hospital stays. The wartime experience
offers a model of alternatives to legislation for ensuring adequate care of
postpartum women.
PMID- 10191810
TI - Reinventing the field training experience: building a practical and effective
graduate program at the UCLA School of Public Health.
PMID- 10191811
TI - Larimer County Tobacco and Youth Project.
PMID- 10191812
TI - Is epidemiology an applied science or a technology?
PMID- 10191813
TI - Directly observed therapy for tuberculosis.
PMID- 10191814
TI - Does directly observed therapy work?
PMID- 10191815
TI - Directly observed therapy and tuberculosis treatment completion. Bloch re: Bayer
et al.
PMID- 10191816
TI - Directly observed therapy and tuberculosis treatment completion. Jereb et al. re:
Bayer et al.
PMID- 10191817
TI - Directly observed therapy and tuberculosis treatment completion. Novick and
Lipsman re: Bayer et al.
PMID- 10191818
TI - Directly observed therapy and tuberculosis treatment completion. Frieden re:
Bayer et al.
PMID- 10191819
TI - [Tuberculosis: epidemiologic development and resistance situation].
PMID- 10191820
TI - [Spectrum of neurological symptoms in dissections of brain-supplying arteries].
AB - BACKGROUND AND OBJECTIVE: Dissection of extracranial arteries that supply the
brain is a common cause of ischemic stroke in youngish persons. Yet this disease,
with its warning and early symptoms, is inadequately known among the population
as well as doctors. This study was undertaken to demonstrate the incidence,
severity and sequelae of this condition, important in both routine general and
hospital practice, with particular emphasis on early signs and diagnosis.
PATIENTS AND METHODS: The data from 33 patients (20 men, 13 women, average age 42
[21-72] years) who during one year had been treated in the authors' hospital for
carotid (n = 23) or vertebral (n = 10) artery dissection were analysed. RESULTS:
The admission diagnosis of dissection, based on the history and ultrasound
findings was in almost all cases confirmed by magnetic resonance imaging (wall
haematoma), magnetic resonance angiograhy, computed tomography-angiography or
conventional angiography. Typical warning and early symptoms such as whiplash
sensation unilateral pain in the throat, neck and head or Horner's syndrome were
elicited in nearly 50% of patients, while known causes such as trauma or
connective tissue disease were confirmed in only 27%. Neurological deficits of
ischemic infarction, some of them severe, persisted in two-thirds of patients,
brain death occurred in one. CONCLUSIONS: Dissection of carotid or vertebral
arteries is a statistically and medically relevant cause of stroke in youngish
persons that can be diagnosed by attention to typical warning and early symptoms
and the performance of noninvasive tests. The often life-threatening sequelae of
possible cerebral ischemia can be diagnosed and even averted by early recognition
of the cause.
PMID- 10191821
TI - [Obstructive sleep apnea syndrome caused by occupational exposure to solvents].
AB - HISTORY AND ADMISSION FINDINGS: A 52-year-old man working in a chemical
laboratory was referred with the possible diagnosis of toxic encephalopathy. For
17 years he had been exposed to high concentrations of perchlorethylene and n
butanol vapours which every day had caused acute symptoms of organic solvent
intoxication. Current complaints were autonomic nervous system symptoms, loss of
concentration and memory, and fatigue in the second half of the day. The patient
was obese but in good general condition. INVESTIGATIONS: Neuropsychiatric
examination confirmed the reported loss of concentration and planning ability at
work. The polysomnogram indicated an increased number of largely obstructive
apnoea attacks. DIAGNOSIS, TREATMENT AND COURSE: As the patients had an
obstructive type of sleep apnoea treatment consisted of positive pressure
ventilation at night and weight reduction. The occupational exposure to organic
solvents was the likely cause. CONCLUSIONS: As the symptoms of encephalopathy and
sleep apnoea syndrome overlap, the latter should be considered before an
encephalopathy is diagnosed. Because a rare cause of the sleep apnoea syndrome is
prolonged and marked occupational exposure to organic solvents this should be
asked about in taking the history. If indeed there has been occupational
exposure, it should cease at once and be reported.
PMID- 10191822
TI - [Acquired reactive perforating collagenosis in diabetes mellitus].
AB - HISTORY AND ADMISSION FINDINGS: A 70-year-old woman with type 2B diabetes
mellitus was referred to the dermatology department because of inflammatory skin
changes of unknown origin over the trunk and limbs. On admission follicular and
parafollicular livid-red papulae with central crusts and reddened margins were
noted over the lower legs and the lumbosacral region. INVESTIGATIONS: Further
physical examination revealed no additional abnormalities. Erythrocyte
sedimentation rate was 41/79 mm. The day-time blood-glucose profile was raised
(10.2, 12.6 and 8.6 mmol/l), as was the glycosylated haemoglobin HbA1c (9.0%).
Swabs from fresh lesions gave no evidence of fungal or bacterial infection.
Biopsies revealed areas of widened epidermis with central ulceration filled with
fibrin, granulocytes and collagen fibres. DIAGNOSIS, TREATMENT AND COURSE: The
clinical and histological findings indicated an acquired reactive perforating
collagenosis (dermatosis) which should be judged in relation to the long-standing
diabetes mellitus. The cutaneous changes were covered with salicylate- and
steroid-containing preparations, while individual lesions were excised or removed
by curettage. CONCLUSION: The condition of acquired reactive perforating
collagenosis is, like Kyrle's disease (perforating follicular and parafollicular
hyperkeratotic dermatosis), perforating serpiginous elastosis and perforating
folliculitis classified among the perforating dermatoses. In the presence of
renal failure and (or) diabetes mellitus these dermatoses must be thought of in
the differential diagnosis, in addition to the more frequent pruriginous
conditions, if there are corresponding skin changes.
PMID- 10191823
TI - [Indications for surgical treatment of tremor].
PMID- 10191824
TI - [Practical aspects of diagnosis, treatment and prognosis in chronic heart
failure].
PMID- 10191825
TI - [Sleep-related respiration disorders: their relevance in intensive care
medicine].
PMID- 10191826
TI - [Risk of liver cancer due to peanut butter?].
PMID- 10191827
TI - [Isolated increase of the concentration of intestinal alkaline phosphatase
isoenzyme].
PMID- 10191828
TI - [Thermal baths or sauna use in patients with tumors].
PMID- 10191829
TI - [Increased blood CEA level as initial manifestation of medullary thyroid
carcinoma].
PMID- 10191830
TI - [Axillary excision in clinically node-negative breast carcinoma].
PMID- 10191831
TI - Revisiting the role of fat mass in the life extension induced by caloric
restriction.
AB - One of the most robust observations in the biology of aging is that caloric
restriction (CR) extends life in a variety of species. Although CR results in a
severalfold decrease in fat mass (FM), the role of fat on life extension was
considered to be minimal. Two main reasons accounted for this belief. First,
although increased FM is associated with changes in substrate oxidation and in
glucose homeostasis, in part through the effects of free fatty acids (FFA) and
glycerol, several studies have suggested that longevity is determined independent
of FM. Second, CR has systemic effects on a range of functions including
neurological, endocrine, reproductive, immunological and antineoplastic, none of
which have been historically linked to fat. In the last few years, an explosion
of evidence has demonstrated that fat tissue is a very active endocrine gland
which secretes a variety of peptides (such as leptin and plasminogen activating
inhibitor-1), cytokines (such as tumor necrosis factor), and complement factors
(such as D, C3, and B). This is in addition to the presence of substrates, such
as glycerol and FFA, which are stored and released by fat cells and are known to
have a major role in hepatic and peripheral glucose metabolism. We propose that
many of the systemic effects of CR can now be explained by the chronic effects
related to decreased plasma levels of peptides, cytokines, complement factors,
and substrates. In fact, all of the benefits of CR on the neuroendocrine system
and those related to the improvement in glucose homeostasis can be attributed to
decrease in adipose cells and their products. Other evidence from epidemiological
data in human obesity supports the role of fat mass and its body distribution as
a risk factor for morbidity and mortality in humans due to impaired glucose
metabolism (similar to rodents), for cancer (similar to rodents), and for the
development of atherosclerotic vascular disease (in humans). If all or most of
the life-extending benefits of CR can be attributed to decreased fat stores, the
expression of specific candidate proteins may be explored and manipulated in the
search for the most powerful adipose-dependent signals that modulate life
expectancy.
PMID- 10191832
TI - Cross-sectional and longitudinal analysis of age-associated changes in body
composition of male Brown Norway rats: association of serum leptin levels with
peripheral adiposity.
AB - Aging-associated alterations in body composition are accompanied by changes in
the endocrine system. We evaluated, in male Brown Norway rats, the effects of
aging on body composition and the association with serum levels of leptin,
insulin, and testosterone. Body composition was assessed cross-sectionally in
male rats (3, 8, 17, and 29 months) by a combination of dual energy x-ray
absorptiometry (DEXA) and dissection of specific muscles and adipose depots.
Longitudinal changes in body composition were quantified by DEXA before and after
3 months of ad-libitum feeding. Body weight, lean mass, absolute and percentage
fat increased with age, whereas percentage of lean mass decreased. Leptin and
insulin levels increased with age in proportion to adiposity; the increase in
leptin with age was related to increased total and peripheral, but not visceral,
fat. Testosterone decreased with age, and was associated with decreased lean and
skeletal muscle mass. These findings suggest that alterations in body composition
with age may be due to decreased trophic and increased lipogenic hormones.
Relative to other rodent models, Brown Norway rats undergo shifts in body
composition and in the hormonal milieu that are consistent with changes seen in
aging humans.
PMID- 10191833
TI - Leptin, adipose tissue and aging--is there a role for testosterone?
PMID- 10191834
TI - Altered IGF-I and IGFBPs in senescent male and female rats.
AB - The effects of senescence on muscle characteristics and the insulin-like growth
factor I (IGF-I) pathway were assessed in male and female BN/F344 rats. The mass
and total ATPase activity of gastrocnemius and plantaris muscles were reduced
with age and to a greater extent in males than in females. The mass and total
ATPase activity of soleus muscle were not significantly altered with age.
Circulating IGF-I was also significantly reduced with age, 60% in females and 21%
in males. Circulating IGF-binding protein 3 (IGFBP-3) was reduced with age. In
liver and gastrocnemius muscle, mRNAs for IGF-1, IGFBP-2, and IGFBP-3 were
analyzed in young and aged males of two strains, BN/F344 and Sprague-Dawley. In
BN/F344 rats, liver mRNAs were unchanged with age. Also in BN/F344 rats, muscle
mRNAs for IGFBP-2, and IGFBP-3 displayed nonsignificant trends toward increase
with age. In aged Sprague-Dawley males, liver mRNA for IGF-I was increased 15%
and muscle mRNA for IGFBP-2 was increased 110%. Thus, different age-related
changes in the growth hormone (GH)/IGF pathway occur in males and females between
the sexes and strains. These changes may play a role in the muscle atrophy
associated with senescence.
PMID- 10191836
TI - Perception of postural limits in elderly nursing home and day care participants.
AB - This study explored whether, when compared to young community-dwelling
individuals, elderly nursing home and day care participants have less accurate
perceptions of their postural stability borders (postural limits). Subjects
estimated their performance before executing maximum forward reaches while
maintaining the feet stationary. Whereas young subjects tended to underestimate
their reaching limits, elderly subjects displayed no significant difference
between estimated and actual values. Furthermore, errors in estimated reach
limits associated with reaching ability, with less-able reachers tending to more
greatly overestimate their abilities. This suggests that elderly nursing home and
day care participants, and especially those with impaired postural limits, lack
the potential "safety factor" observed in young subjects of underestimating their
stability borders. Therefore, the link between decreased postural limits and
falls in older persons may in part be due to lack of awareness of such declines,
and the resulting tendency to plan movements which create loss of balance.
PMID- 10191835
TI - The age-dependent cytokine production by murine CD8+ T cells as determined by
four-color flow cytometry analysis.
AB - Flow cytometry has been used to simultaneously examine intracellular cytokine
production and expression of CD44 and CD45RB by murine CD8+ T cells derived from
young (2-3 months) or aged (18-22 months) mice. Cytokine production by aged CD8+
T cells differs from that by CD8+ T cells derived from young animals in that a
significantly higher percentage of the aged can be triggered to produce
interleukin (IL)-4, interferon (IFN)-gamma, and tumor necrosis factor alpha (TNF
alpha). Conversely, a greater fraction of young CD8+ T cells produce IL-2. Aged
mice not only have a higher percentage of CD8+/CD44hi T cells, but also a larger
fraction of these cells are IFN-gamma+ and IL-4+, while a lower fraction are IL
2+ than is observed in young CD8+/CD44hi T cells. In terms of relative
contribution to total cytokine synthesis, a greater fraction of CD8+ T cells
produce IFN-gamma and IL-4 than in CD4+ T cells, whereas CD4+ T cells are the
major producers of IL-2.
PMID- 10191837
TI - Thyroid hormones: positive relationships with cognition in healthy, euthyroid
older men.
AB - BACKGROUND: Although the association of clinical hypothyroidism with cognitive
deficits is well known, the cognitive effects of thyroid hormones in euthyroid
subjects are less studied and understood. The purpose of this study was to
examine thyroid-cognition relationships in healthy, euthyroid older men. METHODS:
We examined healthy men (N = 44, mean age = 72), excluding clinically
hypothyroid/hyperthyroid or diabetic/hyperglycemic subjects and those with
dementia, depression, CNS medications, or recent illness. Plasma samples obtained
across a 24-hour period were pooled, then assayed for total thyroxine (TT4),
total triiodothyronine (TT3), and T3 resin uptake. Free thyroxine index (FT4I)
was calculated. A broad cognitive battery (including the Wechsler Adult
Intelligence Scale-Revised [WAIS-R], the Dementia Rating Scale [DRS], and the
Rivermead Behavioral Profile [PROFILE]) was administered to all subjects.
RESULTS: Regression analyses controlling age and education showed TT4 and FT4I to
have significant positive relationships with measures of overall cognition; TT4
accounted for 8% to 12% of the variance in omnibus cognitive measures such as
WAIS Performance, WAIS Verbal score, and GLOBAL cognitive scores. CONCLUSIONS:
Our findings suggest that within "normal" range of variation in plasma thyroid
hormones, TT4 but not T3 positively associates with general cognition in healthy
elderly men.
PMID- 10191838
TI - Long-term efficacy of nonsurgical urinary incontinence treatment in elderly
women.
AB - BACKGROUND: Although urinary incontinence affects up to 35% of community-dwelling
elderly women, the long-term efficacy of conservative treatment in this
population is unknown. METHODS: Between April 1991 and January 1994, 81 community
dwelling women over age 60 underwent nonsurgical incontinence treatment that
included pelvic muscle exercises, bladder retraining, estrogen replacement,
biofeedback, functional electrical stimulation, and pharmacologic therapy.
Information about intercurrent medical problems, urogynecologic diagnoses,
treatment recommendations, and provider-documented outcome were collected from
medical records. We mailed structured questionnaires evaluating persistent
incontinence, treatment efficacy, interval therapy, and quality of life to women
who had last attended clinic at least one year previously. RESULTS: Fifty-three
of 81 (65%) women, mean age (+/- SD) 76 +/- 8 years, returned the questionnaire.
The mean follow-up interval was 21 +/- 8 months. At follow-up, 43% of women
reported incontinence was not a problem or mild, 33% reported moderate
incontinence, and 21% reported severe incontinence. When patients compared their
initial with current incontinence severity, improvement was significant (p <
.01). Genuine stress incontinence was diagnosed in 18 women, detrusor
overactivity in 14, and mixed incontinence in 13. Improvement did not vary
consistently by incontinence diagnosis. Older patients had more severe
incontinence at presentation (r = .94, p = .02) and reported less improvement (r
= .97, p < .01) than younger ones. However, the overall likelihood of improvement
was greatest among patients with the most severe incontinence at presentation (r
= .534, p < .001). Subjects considered pelvic muscle exercises, delayed voiding,
and caffeine restriction most effective in reducing incontinence severity.
CONCLUSIONS: Elderly women derive long-term clinical benefit from nonsurgical
incontinence therapy. Younger patients and those with more severe incontinence
are most likely to respond to treatment.
PMID- 10191839
TI - Sensory organization for balance: specific deficits in Alzheimer's but not in
Parkinson's disease.
AB - BACKGROUND: The cause of frequent falling in patients with dementia of the
Alzheimer type (AD) is not well understood. Distraction from incongruent visual
stimuli may be an important factor as suggested by their poor performance in
tests of shifting visual attention in other studies. The purpose of this study
was to determine whether AD patients have difficulty maintaining upright balance
under absent and/or incongruent visual and other sensory conditions compared to
nondemented healthy elderly persons and individuals with Parkinson's disease
(PD). METHODS: Seventeen healthy older adults, 15 medicated PD subjects, and 11
AD subjects underwent the Sensory Organization Test protocol. The incidence of
loss of balance ("falls"), and the peak-to-peak amplitude of body center of mass
sway during stance in the six sensory conditions were used to infer the ability
to use visual, somatosensory, and vestibular signals when they provided useful
information for balance, and to suppress them when they were incongruent as an
orientation reference. Vestibular reflex tests were conducted to ensure normal
vestibular function in the subjects. RESULTS: AD subjects had normal vestibular
function but had trouble using it in condition 6, where they had to concurrently
suppress both incongruent visual and somatosensory inputs. All 11 AD subjects
fell in the first trial of this condition. With repeated trials, only three AD
subjects were able to stay balanced. AD subjects were able to keep their balance
when only somatosensory input was incongruent. In this condition, all AD subjects
were able to maintain balance whereas some falls occurred in the other groups. In
all conditions, when AD subjects did not fall, they were able to control as large
a sway as the healthy controls, except when standing with eyes closed in
condition 2: AD subjects did not increase their sway whereas the other groups
did. In the PD group, the total fall incidence was similar to the AD group, but
the distribution was generalized across more sensory conditions. PD subjects were
also able to improve with repeated trials in condition 6. CONCLUSION: Patients
with dementia of the Alzheimer type have decreased ability to suppress
incongruent visual stimuli when trying to maintain balance. However, they did not
seem to be dependent on vision for balance because they did not increase their
sway when vision was absent. Parkinsonian patients have a more general balance
control problem in the sensory organization test, possibly related to difficulty
changing set.
PMID- 10191840
TI - Postural set for balance control is normal in Alzheimer's but not in Parkinson's
disease.
AB - BACKGROUND: It has been suggested that patients with dementia of the Alzheimer
type have abnormalities in the basal ganglia, and thus, may have similar
sensorimotor problems as patients with basal ganglia degeneration from
Parkinson's disease. Whether the similarity extends to balance control is
unknown. One distinguishing feature of balance disorder in Parkinson's disease is
difficulty with changing postural set in terms of adapting the amplitude of leg
muscle activity as a function of support condition. We, therefore, tested whether
patients with Alzheimer's disease without extrapyramidal signs would show a
similar problem in changing postural set as patients with Parkinson's disease.
METHODS: The ability to quickly change postural set was measured by comparing leg
muscle activity under two conditions of support (free stance, versus grasping a
frame, or sitting) during backward surface translations, during toes up surface
rotations, and during voluntary rise to toes. Results were compared among 12
healthy adults, 8 nondemented Parkinson's patients on their usual dose of
medication, and 11 Alzheimer patients without extrapyramidal signs. RESULTS:
Subjects with Alzheimer's, but not Parkinson's, disease performed similarly to
the healthy control subjects. They changed postural set immediately, by
suppressing leg muscle activity to low levels when supported. Parkinson subjects
did not change postural set immediately. They did not suppress the tibialis
anterior in voluntary rise to toes when holding, nor the soleus in perturbed
sitting as much as the healthy control and Alzheimer subjects in the first trial.
Instead, the Parkinson subjects changed set more slowly, over repeated and
consecutive trials in both protocols. The onset latencies of soleus responses to
backward surface translations and perturbed sitting, as well as tibialis anterior
responses to toes up rotations, were the same for all three groups. CONCLUSION:
Alzheimer patients without extrapyramidal signs, unlike nondemented Parkinson's
disease patients, have no difficulty in quickly changing postural set in response
to altered support conditions. Our results, therefore, do not support the
hypothesis that Parkinson's and uncomplicated Alzheimer's diseases share common
postural set problems that may contribute to disordered balance control.
PMID- 10191841
TI - Do respiratory symptoms predict chronic airflow obstruction and bronchial
hyperresponsiveness in older adults?
AB - BACKGROUND: Respiratory symptoms are common in older adults. In young populations
the predictive value of such symptoms for chronic airflow obstruction and
bronchial hyperresponsiveness is low. We investigated whether symptoms predict
airflow obstruction and bronchial responsiveness in adults aged 45-86 years.
METHODS: An age-stratified random sample of white adults aged 45 years and older
was obtained from family doctor lists in Central Manchester, UK, and sent a
respiratory symptoms questionnaire (exclusions: housebound, confused). Responders
were invited to participate in a methacholine challenge (Newcastle dosimeter
method; exclusions: ischemic heart disease, oral steroids, anticholinergic or
beta-blocker medication). RESULTS: Of 783 eligible subjects, 723 responded
(response rate 92.3%). Symptoms were reported by 53.8%. Methacholine challenge
was completed by 208 subjects. Sixty-five (26.4%) had chronic airflow
obstruction, of whom 76.6% reported respiratory symptoms. Bronchial
hyperresponsiveness (PD20 < or = 100 micrograms) was present in 26.0% of subjects
overall, and in 36.8% of symptomatic and 14.6% of asymptomatic subjects (p <
.001). Of those with bronchial hyperresponsiveness, 26.4% were asymptomatic.
Predictive values of symptoms for chronic airflow obstruction and bronchial
hyperresponsiveness were low. CONCLUSIONS: Respiratory symptoms, chronic airflow
obstruction, and bronchial hyperresponsiveness were all common in this adult
population sample. However, the predictive value of symptoms for airflow
obstruction/bronchial hyperresponsiveness was low. It was concluded that
respiratory symptoms do not identify adults with airflow obstruction or bronchial
hyperresponsiveness. Investigation by spirometry and peak flow monitoring is
necessary to guide appropriate management.
PMID- 10191843
TI - Adult ontogeny of rat working memory of social interactions.
AB - BACKGROUND: Social memory has features that may make it uniquely appropriate for
studying normal aging. We used a cross-section experimental design with an animal
model to survey the lifetime adult ontogeny of memory of a brief social
interaction. METHODS: Groups of healthy adult male rats representing young
adulthood (5 months), middle age (10 months), or old age (19-27 months) were
tested weekly over a month in two paradigms. Basic social memory and social
interference memory were quantified by differences between investigation times of
a juvenile rat during a 5-min interaction (acquisition trial) and a second
exposure (recall testing), with interexposure intervals (IEI) ranging from 15 min
to 24 h. RESULTS: Although basic social memory of all age groups was similar at
the brief or longer IEI, there were memory declines at intermediate IEI delays in
older males, especially the oldest groups. Decrements to working memory appeared
as early as middle-age when an unfamiliar juvenile was inserted between
acquisition and recall testing. Nonetheless, our healthy old animals retained a
robust ability to recall identity of a conspecific that a minute by minute
comparison suggested involves similar behavioral means of gathering social
information. CONCLUSIONS: Normative aging of working social memory in male rats
can be characterized as being more fragile, beginning at middle age but without
significant further decline until near the end of the life span. Functional
impact of these age-dependent changes in social memory, on the other hand, may be
minimal for all but the very oldest animals in the social group.
PMID- 10191842
TI - Effects of age on balance assessment using voluntary and involuntary step tasks.
AB - BACKGROUND: Taking a step while standing and modifying a step while walking are
two strategies often used to maintain balance when balance disturbances are
encountered during activities of daily living. This study investigated whether
performance on an involuntary step task, which is assumed to be a surrogate for
fall recovery abilities, was comparable to performance on a voluntary step task.
METHODS: The performance of a voluntary and an involuntary step task was measured
in healthy young adult (mean age 21 years) and healthy elderly adult (mean age 68
years) female subjects. Subjects stepped as fast as possible in the direction of
a minimally destabilizing lateral waist pull (voluntary step task), or they
responded naturally to a large destabilizing lateral waist pull (involuntary step
task). The effects of age, task, and their interaction on the primary outcome
variables of step foot liftoff time, landing time, step length, and step height
were examined. RESULTS: In the voluntary step task, the older adults, compared to
the young, required significantly more time to lift their foot (Young: 307 msec;
Elderly: 424 msec). In the involuntary step task, the elderly were as quick as
the young in lifting their foot (Young: 322 msec; Elderly: 335 msec). The young
lifted their foot at about the same time for the two tasks. The elders, on the
other hand, lifted their foot significantly earlier in the involuntary step task,
compared to the voluntary step task (Vol: 424 msec; Invol: 335 msec).
CONCLUSIONS: A voluntary step task underestimates the ability of healthy elderly
adults to respond quickly when large destabilizing balance disturbances are
encountered.
PMID- 10191844
TI - Cognitive impairment and depression predict mortality in medically ill older
adults.
AB - BACKGROUND: Depression and cognitive impairment are common in medically ill older
adults. Few studies, however, have investigated the roles of both in predicting
mortality for medically ill older adults. METHODS: We used a cohort of
consecutive patients aged 60 or older admitted to a rehabilitation hospital (N =
667) of whom 455 completed a standardized protocol measuring cognition (Dementia
Rating Scale), depression (Geriatric Depression Scale), and disabilities
(Functional Independence Measure). Burden of medical illnesses was measured with
the Charlson Index. Vital status was assessed one year later. RESULTS: Those
subjects who did not complete the screening were more likely to die (24% vs 17%;
p = .02) during the one-year follow-up. Of those who completed the screening,
male sex (odds ratio [OR] = 1.84), depression (mild OR = 1.64; moderate OR =
2.49), and more severe cognitive impairment (OR = 2.13) predicted mortality
independent of age, medical illnesses, or disabilities. No interaction of
cognitive impairment and depression was detected. In those subjects cognitively
intact, moderate depression (OR = 4.95) and male sex (OR = 3.42) were independent
risk factors for dying. In those subjects without depression, male sex (OR =
2.24) and elevated Charlson Index (OR = 1.42) predicted mortality. CONCLUSIONS:
Depression and cognitive impairment are independent predictors of one-year
mortality in this subgroup of medically ill older adults.
PMID- 10191845
TI - Contribution of psychosis and depression to behavioral disturbances in
geropsychiatric inpatients with dementia.
AB - BACKGROUND: Specific behavioral disturbances in dementia may be associated with
underlying disorders such as the presence of psychosis and depression. The
objective of this study was to examine the association of depression and
psychosis with behavioral disturbances in geropsychiatric inpatients with
dementia. METHODS: All admissions between October 1993 and May 1995 were reviewed
to identify those patients admitted to the Houston Veterans Affairs
Geropsychiatry Unit with a diagnosis of dementia; 208 patients were included in
the study. Hierarchical regression models were constructed to explore the
contribution of depressive and psychotic symptoms, and depression and psychosis
diagnoses to Cohen-Mansfield Agitation Inventory (CMAI) scores. RESULTS: Both
depression and psychotic symptoms were significantly and positively correlated
with behavioral disturbances. Psychotic symptoms were associated with aggressive
behavioral symptoms, and depressive symptoms were associated with constant
requests for help, complaining, and negativism. Dementia severity accounted for
significant variance in CMAI scores and was positively associated with behavioral
disturbance; though disorder symptoms accounted for more behavioral disturbance
variance than did depressive symptoms. CONCLUSIONS: Both depressive and psychotic
symptoms were associated with overall behavioral disturbances in patients with
dementia. Psychotic symptoms and depressive symptoms were associated with
different types of behavioral disturbances. Our findings support the contention
that underlying depression or psychosis may partially account for different
behavioral disturbances and that not all behavioral disturbances should be
globally labeled "agitation." Future studies should address symptom-specific
treatment of behaviorally disturbed patients.
PMID- 10191846
TI - Hydration during labour--a recipe.
PMID- 10191850
TI - Community service.
PMID- 10191847
TI - The mother-to-child HIV transmission debate.
PMID- 10191849
TI - The mother-to-child HIV transmission debate.
PMID- 10191851
TI - National Institute of Virology report on testing of Virodene by the NIV.
PMID- 10191853
TI - South Africa's health reviewed.
PMID- 10191854
TI - Tell all on Virodene.
PMID- 10191852
TI - Public safety delays putting Viagra on the shelf.
PMID- 10191855
TI - Virodene down but not out.
PMID- 10191856
TI - The brave New World of medicine.
PMID- 10191857
TI - Bell the CAT: proposals to regulate all medical equipment.
PMID- 10191858
TI - Uncontrolled funding at root of high-tech abuse.
PMID- 10191859
TI - What obstacles to TB control?
PMID- 10191860
TI - Public-private partnerships in academic medicine--an 'ideal nation' model.
PMID- 10191861
TI - Specialised surgery and preoperative radiotherapy improve outcome in rectal
cancer.
PMID- 10191862
TI - Withdrawal of chlormezanone-containing products.
PMID- 10191863
TI - Recommendations pertaining to the use of viral vaccines: influenza.
PMID- 10191864
TI - Pneumopericardium.
PMID- 10191865
TI - Examination of the urine.
PMID- 10191866
TI - Should AIDS be notifiable?
PMID- 10191867
TI - Health care technology assessment--the South African health care system in
transition.
PMID- 10191868
TI - Eight years of tuberculosis research in Hlabisa--what have we learned?
AB - An 8-year research-service collaboration in tuberculosis (TB) in Hlabisa has
yielded important data on the emerging HIV-related TB epidemic in South Africa,
demonstrating a substantial increase in caseload, HIV prevalence and mortality. A
successful, cost-effective, community-based programme of directly observed
therapy, utilising volunteers, clinics and community health workers, has helped
ensure adherence to therapy. As the caseload has increased, however, case-holding
has started to fall, suggesting the need for more effective defaulter-tracing
strategies. More fundamental work has studied the molecular epidemiology of TB,
suggesting that much of the disease is recently, and casually, transmitted. This
collaborative experience may be a model for efforts to control other important
public health problems.
PMID- 10191869
TI - Hypertension management of medical aid patients attending private practices.
AB - OBJECTIVES: The study aimed to describe the treatment status of hypertensive
patients and the prescribing patterns of private medical practitioners treating
medical aid scheme patients with hypertension. METHOD: Data on hypertensive
patients belonging to medical aid schemes were provided to the drug utilisation
review consultancy, Quality Health Services (QHS), by private medical
practitioners. The data were computerised and included the age and gender of the
patient, the diastolic and systolic blood pressure (BP), the medication
prescribed for the condition and the qualifications of the reporting doctor. All
the prescribed drugs were categorised into 12 drug classes and combination
preparations had each constituent categorised. The level of BP allowed the degree
of BP control to be described as controlled (< 140/90 mmHg), borderline (140/90-<
160/95 mmHg) and uncontrolled (> or = 160/95 mmHg). RESULTS: Included in the
study were 11,696 hypertensive patients (46.3% male and 53.7% female) and the
3,503 doctors who cared for them. The systolic BP showed an age-related increase,
but the diastolic BP did not. The level of BP control was high, with less than a
quarter of patients having uncontrolled hypertension. The most frequently
prescribed drug class was angiotensin-converting enzyme (ACE) inhibitors (32.2%).
Beta-blockers accounted for 20.8% and calcium antagonists for 14% of all
prescriptions. Thiazide and thiazide-like diuretics on their own accounted for
only 7.8% of prescriptions. However, a further 13.8% of prescriptions contained
this class of diuretics in combination with other drug classes. Diuretics of all
classes taken on their own or in combination were used by 33.9% of patients.
CONCLUSIONS: Good levels of hypertension control were reported for hypertensive
patients by their private practitioners. Almost half of all prescriptions were
for the newer and more costly antihypertensive drugs (ACE inhibitors and calcium
antagonists), although their effectiveness in reducing long-term complications of
hypertension is still unproven. Furthermore, these prescribing patterns do not
conform to those recommended by the Southern African Hypertension Society's
hypertension management guidelines.
PMID- 10191870
TI - Constraints facing the female medical practitioner in private family practice in
the Western Cape.
AB - OBJECTIVES: To assess the existence and extent of employment-related problems
facing female family practitioners in the context of a rapidly growing number of
female doctors in South Africa. SUBJECTS AND METHODS: A descriptive survey was
conducted using bilingual questionnaires. These were posted to all 280 female
family practitioners in private practice in the Western Cape. RESULTS: Of the 280
questionnaires posted 169 were returned, but 45 of these were missampled. A
response rate of 53% was obtained. The largest age category was 30-39 years. Of
those not in solo practice, 68 (75%) were able to negotiate the terms of their
working hours, 13 (19%) negotiated sick leave on commencing work, and only half
had paid leave. Vacation leave was negotiated by 34 (50%), while only 6 (9%)
discussed maternity leave with employers or colleagues. Of the 124 practices
included in the survey, 6 (5%) had formal arrangements to cope with maternity
leave. One hundred and seven respondents (86%) felt there was a need for
maternity leave guidelines in the private sector in South Africa. Regarding
practice-related problems, 33 female family practitioners (27%) reported some
incidents of sexual harassment by patients. Despite these constraints, 88
respondents (71%) planned to continue working in this field. CONCLUSION: Definite
obstacles exist in private family practice with regard to working conditions, in
particular the lack of national regulations regarding maternity leave and the
absence of legislation on pregnancy discrimination. This has important
implications for the inclusion of female doctors in group practices and managed
health care organisations--private primary health care of the present and future!
PMID- 10191871
TI - Antimalarial prophylaxis--use and adverse events in visitors to the Kruger
National Park.
AB - OBJECTIVES: To determine the use of antimalarial prophylaxis and the relative
frequency of adverse events with different regimens in visitors to the Kruger
National Park. DESIGN: Retrospective postal survey of a cohort of 7,397 visitors
during April 1996. Telephonic interviews were conducted with all respondents who
reported neuropsychiatric adverse events necessitating medical attention, and
their medical caregivers. RESULTS: The most commonly used regimens were
chloroquine and proguanil in combination (C&P) (35.6%) and mefloquine (18.4%).
However, non-recommended regimens were also used by travellers to this
chloroquine-resistant area, including chloroquine alone (15.7%). Adverse events
were reported by 23.8% of travellers and were more common in the C&P group than
the mefloquine group (28.9% v. 25.0%, P = 0.0100). Gastro-intestinal side-effects
were significantly more common in the C&P group (nausea (P = 0.0170), diarrhoea
(P = 0.0008), mouth ulcers (P = 0.0000)), while neuropsychiatric side-effects
were more common in the mefloquine group (depression (P = 0.0000), light
headedness (P = 0.0009), anxiety (P = 0.0060)). Only 30% of travellers reported
using antimalarial drugs both regularly as prescribed and for 4 weeks after
leaving the malaria area. The most commonly reported reason for changing
prophylaxis was advice from a physician or pharmacist (41.9%). CONCLUSIONS:
Health professionals providing medical advice to prospective travellers to
malarious areas must tailor recommendations based on the balance between malaria
risk in a specific geographical area and the benefits and tolerance of protective
measures. Mosquito-avoidance measures should always be advocated, but counselling
on antimalarial prophylaxis will be guided by the malaria/prophylaxis (serious
adverse events) risk ratio. Where drug measures are indicated, the importance of
their correct use should be emphasised.
PMID- 10191872
TI - Factor V Leiden gene mutation in three South African families.
PMID- 10191878
TI - Finding out about filling-in: a guide to perceptual completion for visual science
and the philosophy of perception.
AB - In visual science the term filling-in is used in different ways, which often
leads to confusion. This target article presents a taxonomy of perceptual
completion phenomena to organize and clarify theoretical and empirical
discussion. Examples of boundary completion (illusory contours) and featural
completion (color, brightness, motion, texture, and depth) are examined, and
single-cell studies relevant to filling-in are reviewed and assessed. Filling-in
issues must be understood in relation to theoretical issues about neural
perceptual isomorphism and linking propositions. Six main conclusions are drawn:
(1) visual filling-in comprises a multitude of different perceptual completion
phenomena; (2) certain forms of visual completion seem to involve spatially
propagating neural activity (neural filling-in) and so, contrary to Dennett's
(1991; 1992) recent discussion of filling-in, cannot be described as results of
the brain's "ignoring an absence" or "jumping to a conclusion"; (3) in certain
cases perceptual completion seems to have measurable effects that depend on
neural signals representing a presence rather than ignoring an absence; (4)
neural filling-in does not imply either "analytic isomorphism" or "Cartesian
materialism," and thus the notion of the bridge locus--a particular neural stage
that forms the immediate substrate of perceptual experience--is problematic and
should be abandoned; (5) to reject the representational conception of vision in
favor of an "enactive" or "animate" conception reduces the importance of filling
in as a theoretical category in the explanation of vision; and (6) the evaluation
of perceptual content should not be determined by "subpersonal" considerations
about internal processing, but rather by considerations about the task of vision
at the level of the animal or person interacting with the world.
PMID- 10191879
TI - Processing capacity defined by relational complexity: implications for
comparative, developmental, and cognitive psychology.
AB - Working memory limits are best defined in terms of the complexity of the
relations that can be processed in parallel. Complexity is defined as the number
of related dimensions or sources of variation. A binary relation has one argument
and one source of variation; its argument can be instantiated in only one way at
a time. A binary relation has two arguments, two sources of variation, and two
instantiations, and so on. Dimensionality is related to the number of chunks,
because both attributes on dimensions and chunks are independent units of
information of arbitrary size. Studies of working memory limits suggest that
there is a soft limit corresponding to the parallel processing of one quaternary
relation. More complex concepts are processed by "segmentation" or "conceptual
chunking." In segmentation, tasks are broken into components that do not exceed
processing capacity and can be processed serially. In conceptual chunking,
representations are "collapsed" to reduce their dimensionality and hence their
processing load, but at the cost of making some relational information
inaccessible. Neural net models of relational representations show that relations
with more arguments have a higher computational cost that coincides with
experimental findings on higher processing loads in humans. Relational complexity
is related to processing load in reasoning and sentence comprehension and can
distinguish between the capacities of higher species. The complexity of relations
processed by children increases with age. Implications for neural net models and
theories of cognition and cognitive development are discussed.
PMID- 10191880
TI - [Symptomatological patterns of infancy diseases. Presentation of a new Symptom
Checklist].
AB - BACKGROUND: Recently it is often very frequent a request of specialist
consultation for children with psychic discomfort expressed through somatic
complaints and/or behavior disorders. The real meaning of these symptoms in terms
of prognosis, is not clear; indeed they can be the first signs of a poor
prognosis of developmental disorders or a transient developmental crisis. The
objective of this study is the evaluation of a Symptom Checklist as an instrument
which allows to point out the somatic complaints and the behavior disorders of
Italian children aged less than 48 months and to identify symptoms patterns which
label the main neurological and psychiatric diseases in that age. METHODS: The
Symptom Checklist has been used transversely in a clinical sample of 30 subjects
(24 males and 6 females) aged less than 48 months with developmental linguistic
disorder, born prematurely or with a developmental pervasive disorder and in a
control sample of 37 children (21 males and 16 females). RESULTS AND CONCLUSIONS:
The results obtained, matching every single group to each other and every single
group to the control group, identify symptoms pattern (somatic or behavioral)
specific for each clinical condition examined; therefore, the clinical utility of
Symptom Checklist in pointing out in infancy psychiatric risk cases for a poor
prognosis is confirmed.
PMID- 10191881
TI - [Sepsis caused by Streptococcus pneumonia in newborn infants. 2 case reports].
AB - Streptococcus pneumoniae is responsible for 2% of all neonatal sepsis. The
results of epidemiological studies suggest that newborns acquire infection by the
ascending route or during the passage through the birth canal. It has been
hypothesized that colonization of the maternal genital tract with S. pneumoniae
might be caused by contamination of obstetric instruments with the microorganism
or by sexual practices, particularly oro-genital contact. From our NICU's
database, two cases of newborn sepsis due to Streptococcus pneumoniae, occurred
between 1988 and 1996 have been found; the first case presented a fatal
disseminated intravascular coagulation (DIC), the second a severe respiratory
failure. Antibiotic treatment of women carrying S. pneumoniae in the genital
tract and their infants should be strongly recommended, on the basis of the
potentially serious consequences for the infants.
PMID- 10191882
TI - [Pediatrics and puericulture in ancient Greece].
PMID- 10191883
TI - [Pharyngeal and nasal swabs in upper airway infections in children.
Considerations on results obtained at a Pediatric Unit during 1 year].
PMID- 10191884
TI - [Cognitive functions in Turner's syndrome].
AB - BACKGROUND: In this article, the interrelations between biological and emotional
factors in learning disabilities in Turner's syndrome are studied. METHODS: This
is a transversal study with a 18 months neuropsychiatric follow-up. Five girls
with the syndrome, aged between 12 and 22 years have been studied using Wechsler
scales (WISC-R and WAIS), individual interviews and psychodiagnostic tests, to
describe both their cognitive profile and psychological traits. RESULTS: The
intelligence tests show selective impairments in visuo-spatial area, with lower
score on performance IQ, especially in the sub-tests "Block Design" and "Object
Assembly"; individual interviews and psychodiagnostic tests show signs of
psychological disease, often consequences of this syndrome, and only in one girl
with an associated diagnosis of psychosis. CONCLUSIONS: Psychological and
environmental factors, as well as the genetics, may play an important role in the
impairment of cognitive abilities, and the neuropsychological aspects may not be
related only with the organic substrate.
PMID- 10191885
TI - [Group A beta-hemolytic streptococcus infection and varicella].
AB - The case of a 3-year-old boy affected with varicella associated to acute
cellulitis by group A beta-hemolytic streptococci is reported. The causes of
hospitalization were: high fever, decline of condition, onset of scarlet
exanthema and a severe swelling in the inguinoscrotal area, during varicella. The
diagnosis of streptococcal infection was confirmed by positive pharyngeal tampon,
scarlet exanthema and following rise of ASLO. Since the association of these two
infections is reported in literature more and more frequently, the possible
causes and precautionary measures are analysed.
PMID- 10191886
TI - [Pediatrics and puericulture in the Roman world].
PMID- 10191887
TI - [What is the role today for general pediatrics?].
PMID- 10191888
TI - [Protection of children in cars: integrating the specifics].
PMID- 10191889
TI - [Extracorporeal lithotripsy in children. Study of its efficacy and evaluation of
renal parenchymal damage by DMSA-Tc 99m scintigraphy: a series of 39 children].
AB - AIM: The objectives of the study were to confirm the efficacy of extracorporeal
shock wave lithotripsy (ESWL) in infants and children and to evaluate potential
long-term renal parenchymal damage by 99m Tc DMSA renal scan. MATERIALS AND
METHODS: Between November 1989 and November 1997, 39 children between 10 months
and 17-1/2 years of age (average: 7 years) were treated by extracorporeal shock
wave lithotripsy for kidney or ureteral stones with a Sonolith 3000 lithotriptor
(Technomed Corp). Forty-six stones were treated. Eight metabolic and 11
urological abnormalities were identified. The evaluation of the treatment and its
consequences were based on a clinical examination, conventional imaging and a
DMSA renal scan performed 24 h before extracorporeal shock wave lithotripsy and
at least 6 months after treatment. RESULTS: Treatment was successful (stone
fragmented and eliminated) in 84.6% at 3 months after one to four sessions. Sixty
one sessions were necessary and two patients underwent open surgery for failed
extracorporeal shock wave lithotripsy. Three recurrences were also retreated. At
long term follow-up (6 months to 8 years) no incidents of high blood pressure
were observed, nor parenchymal lesions imputable to extracorporeal shock wave
lithotripsy. CONCLUSIONS: The efficacy of the extracorporeal shock wave
lithotripsy for children is proven. This study also confirms the innocuousness of
extracorporeal shock wave lithotripsy for renal parenchyma even in infants.
However, long term follow-up and further evaluation with the other categories of
lithotriptors are necessary to make definitive conclusions.
PMID- 10191890
TI - [Reagin sensitizations and date of birth. Differences in function according to
family history].
AB - BACKGROUND: Atopy remains a hazy concept, as research in genetic markers is still
not sufficiently elaborated due to multiple physiopathological mechanisms and
mixing of patients. The aim of this work was to demonstrate this hypothesis by
comparing birthdates according to family history and serum IgE to house dust mite
and/or timothy grass pollen. PATIENTS AND METHODS: Rasts d1 and g6 were measured
in the serum of 5,468 subjects, 2 to 18 years of age. The quotient of
sensitizations to Dermatophagoides pteronyssinus and timothy grass pollen was
established, month by month, according to family history. Representative curves
were smoothed by computer. RESULTS: The circannual rhythm of quotients was
remarkably similar within both groups of subjects with or without family history,
with a time lag of 2 to 3 months. Subjects without family history were born 2 to
3 months before subjects with family history, i.e., they were 2 to 3 months older
at the time of antigenic stimulation. CONCLUSIONS: Mechanisms by which subjects
have been sensitized, still unknown, happen in different times according to
family history. These findings suggest several genetic factors.
PMID- 10191891
TI - [Clinical and respiratory function follow-up of 39 infants treated with neonatal
respiratory extracorporeal assistance].
AB - The aim of this prospective study was to evaluate the consequences of neonatal
treatment with a venovenous extracorporeal respiratory assistance. POPULATION AND
METHODS: Thirty nine neonates (28 boys) with acute respiratory failure were
included. Extracorporeal respiratory assistance consisted of an apnoeic
oxygenation with low frequency positive pressure ventilation and extracorporeal
membrane CO2 removal through a venous single canula perfusion circuit. The causes
of respiratory distress were: 15 meconium aspiration syndrome, 12 respiratory
distress syndrome, six hyaline membrane disease, three sepsis, two diaphragmatic
hernia, and one post-surgery Mendelson syndrome. The mean duration of mechanical
ventilation was 18 days, including 5 days of extracorporeal respiratory
assistance. The prospective follow-up included physical examination, chest
radiographs, scintigraphy and pulmonary function tests. These tests studied the
following parameters: functional residual capacity by helium dilution technique,
lung resistance and dynamic lung compliance by the esophageal balloon technique
and blood gases with arterialized blood samples. RESULTS: The mean duration of
the follow-up was 21.3 months (6 months to 5 years). Results showed in the first
year 33% of children with chronic obstructive pulmonary disease and chest (X-ray
abnormalities, such as bronchopulmonary dysplasia in 23% of children. Data of
pulmonary function test at the end of the first year: lung resistance and
functional residual capacity were within limits of predicted values for height,
and dynamic lung compliance was slightly decreased; according to the analysis of
the functional profile: 31% without abnormality, 41% of obstructive syndrome and
26% with restrictive pattern. Blood gases were normal in 37 children. At the end
of the second year, we noticed normal functional residual capacity, an increase
of lung resistance while lung compliance was normalized; functional profile was
quite different: with a decrease of the number of patients without abnormality
(22%) and increase of those with obstructive syndrome (56%). CONCLUSION: The
percentage of abnormalities is high but these are moderate in most cases,
especially if we compare with the initial seriousness of the pulmonary pathology.
We suggest a regular follow-up to study the respective incidence of pulmonary
disease and/or extracorporeal respiratory assistance over these abnormalities.
PMID- 10191892
TI - [Treatment of isolated nocturnal enuresis: alarm or desmopressin?].
AB - BACKGROUND: Monosymptomatic nocturnal enuresis is common in healthy school
children. Treatment is often required because of social and psychological
convenience. We therefore conducted a randomized prospective trial using either
desmopressin (D) or alarm (A). PATIENTS AND METHODS: Patients (n = 135) aged 6 to
16 years were enrolled between January 1992 and December 1994. Desmopressin
(Minirin spray, Ferring SA) was given intranasally at a dose of 20 micrograms at
bedtime and increased to 40 micrograms after 2 weeks if partial result was
obtained. The alarm was a pad-bell device (Wet-stop, Sega) and the sound source
was attached to the upper part of the pajamas. Inclusion criteria were: primary
monosymptomatic nocturnal enuresis in healthy children, age > or = 6 years,
absence of previous treatment using either desmopressin or alarm. The aim of the
treatment was to achieve 100% dry nights. Patients were evaluated after 15 days
on therapy by phone call and thereafter by attending the outpatient clinic at 2-3
and 4-6 months. At the time of the second evaluation, a switch from alarm to
desmopressin (or vice-versa) was proposed to those who did not respond to the
initial treatment. RESULTS: In group D (n = 62), only 27 children were included
since 12 (19%) were switched to alarm and 23 (37%) were excluded because they
were either non-compliant or lost to follow-up. In group A (n = 73), only 31 were
included since six (8%) were switched to desmopressin and 36 (49%) were excluded
for the same reasons as in group D. Prior to inclusion, the percentage of dry
nights was 21% in group D and 14% in group A. After 15 days on therapy, patients
from group D achieved 80% dry nights compared to 50% in group A (P = 0.001).
After 3 months, patients from group D attained 85% dry nights vs 90% in group A.
After 6 months, children from group A achieved 94% dry nights vs 78% in group D
(P = 0.01). CONCLUSION: Desmopressin offers better short-term results than
enuresis alarm but the latter is significantly more efficient in the long term.
In France, the alarm device is not reimbursed by the national health service and
therefore is poorly accepted, as suggested from the high rate of patients lost to
follow-up.
PMID- 10191893
TI - [Mycoplasma pneumoniae meningoencephalitis].
AB - BACKGROUND: Severe central nervous system diseases, such as encephalitis, have
been reported in association with Mycoplasma pneumoniae infections. CASE REPORT:
After an ENT infection, a 9-year-old boy with Down's syndrome developed
encephalitis revealed by an acute alteration in consciousness. Head computed
tomography showed, after 2 weeks, an infiltration in the basal ganglia region.
The diagnosis of Mycoplasma pneumoniae encephalitis was made; recovery was
complete in a few weeks. CONCLUSION: Mycoplasma pneumoniae infection should be
considered in all cases of acute encephalopathy; yet the pathogenesis of the
disorder is unknown and the treatment uncertain.
PMID- 10191895
TI - [Myocardiopathy and isolated glucocorticoid deficit with ACTH resistance: a
fortuitous association?].
AB - Hereditary syndrome of unresponsiveness to ACTH is a rare autosomal recessive
disorder characterized by an isolated glucocorticoid deficiency which is
exceptionally associated to regressive cardiomyopathy. CASE REPORT: A male
newborn had iterative episodes of hypoglycemia since the first hours of life.
Acute bronchiolitis at the age of 14 days was associated with transitory dilated
cardiomyopathy. Hypoglycemia was due to glucocorticoid deficiency secondary to
ACTH insensitivity. Molecular biology showed a composite heterozygotism for the
ACTH receptor gene. CONCLUSION: Any congenital glucocorticoid deficiency should
lead to search for cardiomyopathy.
PMID- 10191894
TI - [Antithrombin deficiency and thrombosis in a young child].
AB - BACKGROUND: Thromboses represent a rare event in children and may be due to a
deficiency of antithrombin. CASE REPORT: A 10-year-old boy developed thrombosis
due to a congenital quantitative deficiency in antithrombin, confirmed by
molecular biology. His father was diagnosed with the same deficiency. The child
was first treated with heparin and is now on antivitamin K. He is well 26 months
after diagnosis. CONCLUSION: When a young patient presents with a thrombotic
event, a congenital deficiency in one of the inhibitors of coagulation, one of
which is antithrombin, should be looked for and the condition treated as soon as
possible.
PMID- 10191896
TI - [A cause of acute encephalitis: primary infection due to Epstein-Barr virus].
AB - The neurologic complications of Epstein-Barr virus (EBV) primary infection are
frequently overlooked, yet EBV is responsible for some cases of acute
encephalitis. We report on a case of an infant with acute brain-stem encephalitis
during EBV primary infection. OBSERVATION: A 22-month-old boy was admitted to the
hospital for acute neurological symptoms. Initially, he presented ataxia and
dysphagia. During the first days, his neurological status worsened with loss of
consciousness requiring ventilatory support. A progressive improvement appeared
after a 1 week course. One month later, a moderate ataxia was still noted, but 3
months later, the clinical examination was normal. The neuroradiological
explorations revealed damage of the white matter, with high T2-weighed signal on
the first brain magnetic resonance imaging. One month later, the control magnetic
resonance imaging was normal. The diagnosis of EBV encephalitis was based upon
the exclusion of other possible causes and positive serology for EBV, consistent
with acute primary infection. CONCLUSION: EBV infection should be looked for
during the etiologic work-up of an acute encephalitis. The different cases
reported in the literature show a favorable initial outcome, but neurological
relapse and sequelae are possible. No specific treatment is effective.
PMID- 10191897
TI - [Visceral leishmaniasis and malnutrition: a case report].
AB - BACKGROUND: Visceral leishmaniasis occurring in malnourished subjects can have an
uncommon course, which explains difficulties in its diagnosis. CASE REPORT: A 22
month-old infant was admitted because of malnutrition and prolonged fever. The
bacteriological investigation was negative. When his nutritional status improved,
he developed a splenomegaly. The medullogram confirmed the diagnosis of visceral
leishmaniasis. The course was then favorable with treatment by pentavalent
antimonial. CONCLUSION: Malnutrition constitutes a risk factor of opportunist
parasitic disease such as leishmaniasis. Its diagnosis can be very difficult.
PMID- 10191898
TI - [Prion diseases in pediatrics].
AB - Prion diseases are rare neurologic affections with a poor prognosis, occurring in
both humans and animals. Creutzfeldt-Jakob disease (CJD) secondary to human
extracted growth hormone treatment is the most frequent condition in pediatrics.
In 1994, a new type of CJD (variant CJD) was described in young adults in the
United Kingdom, only 10 years after the bovine spongiform encephalopathy
epidemic, with recent works showing a direct relationship between the bovine
epidemic and the human cases. An accumulation of a single protein called the
prion protein (PrP) has been discovered in the brain in all of these cases,
animal and human, leading to the hypothesis that a new infectious agent could
proceed without any nuclear acid information; another hypothesis is that of a
still unknown viral agent. The PRNP gene encoding for this PrP protein is well
described: some mutations and a polymorphism in the 129th codon have been shown
to be implicated in many cases of CJD. PrP is a ubiquitous protein, with yet
unknown physiological function. There are still many questions to be answered:
shall we expect new pediatric cases of variant CJD? Assuming that animal-human
contamination is related to alimentation, are there other ways of contamination.
PMID- 10191899
TI - [KID syndrome (keratitis, ichthyosis and deafness)].
AB - Keratitis, ichthyosis and deafness are the dominant signs of KID syndrome. The
lesions involving cornea, epidermis and internal ear are probably the result of a
congenital ectodermal abnormality. Associated signs such as increased sensitivity
to infections, and dermoskeleton dystrophies are also useful for the diagnosis.
There are no specific biological signs. Most cases are sporadic but familial
cases have been described with unclear mode of inheritance. Treatment is
disappointing. Thus management mainly relies upon early detection of
complications.
PMID- 10191900
TI - [Theoretical bases of semiology in pediatric psychiatry. I. Theoretical models].
AB - This paper is the first part of a study on the theoretic concepts used in child
psychiatry and their functioning during the first consultations with a child and
his family. These models have different origins (medicine, psychology, education)
and contribute to the true specificity of child psychiatry, which must take into
account both the developmental aspect as in pediatrics, and the peculiarity of
the human psyche. This gives a special stamp to child psychopathology and some
usual ways of thinking (like normality, comparability) are quickly inoperative.
The five main theoretic models available in child psychiatry are recalled: the
model of the medical semiology which describes symptoms and gives them value, the
clinical-anatomical model which tries to set up relationships between structure
and function, the developmental and cognitive model which emphasizes the
psychomotor and intellectual abilities of the child, the affective model
(psychoanalysis and attachment) which studies his/her emotional development, and
the environmental model which set the child in his/her conditions of growth.
These models only support the thoughts of the consultant who must keep in mind
the psychic development as a whole and try to aggregate all his findings in the
various fields to extract the main features underlying the child's difficulties.
PMID- 10191901
TI - [Radiologic case of the month. Neurocysticercosis].
PMID- 10191902
TI - [Chlamydia trachomatis conjunctivitis in the newborn].
AB - Infections of the conjunctiva are frequent in the neonatal period. While
Neisseria gonorrhoea and chemical agents were considered as the main etiologies
of ophtalmiae neonatorum in the past, Chlamydia trachomatis is today a major
cause of neonatal conjunctivitis. Thus in a study of 180 uni-or bilateral
neonatal conjunctivitis the authors found a prevalence of Chlamydia trachomatis
infection of 41%. The importance of the etiological diagnosis of neonatal
conjunctivitis is emphasized, in order to define a specific treatment.
Etiological diagnosis of Chlamydia trachomatis infection is based upon
immunofluorescence and molecular diagnosis techniques (PCR, LCR). Prevention of
neonatal Chlamydia trachomatis conjunctivitis relies upon screening and treatment
of Chlamydia trachomatis infections in pregnant women and their partners.
Treatment requires oral macrolides, the topical treatment being ineffective.
PMID- 10191903
TI - [Prevention of antibiotic resistance needs informed parents].
AB - Antibiotic resistance is becoming worldwide a major challenge. Increasing rate of
multidrug resistant bacteria is directly linked with the consumption of
antibiotic. Children are the greatest consumers of antibiotics, but this large
pediatric prescription is not justified, and responds, at least in part, to a
"parental pressure". Therefore information to the parents about antibiotic is
recommended. In order to promote this information the American Academy of
Pediatrics recently wrote a booklet entitled "Your child and antibiotics" which
is presented.
PMID- 10191904
TI - [Inhaled corticosteroids and growth].
AB - Inhaled corticosteroids are effective in patients with asthma by reducing the
chronic inflammatory changes. They are widely prescribed in children and even in
infants. The potential adverse effects of inhaled corticosteroids on statural
growth have been the matter of numerous past and present controversies. Asthma
itself can delay growth. The majority of studies demonstrate that the growth
impairment is dose-dependent and that moderate doses of inhaled corticosteroids
are safe. Monitoring statural growth of asthmatic children, whether they are
treated or not with inhaled corticosteroids is mandatory. The treatment must be
adapted to the severity of asthma, and overtreatment must be avoided. Inhalation
techniques minimizing systemic absorption must be used. Addition of other
antiasthmatic drugs to moderate doses of inhaled corticosteroids should be
preferred to high doses of inhaled corticosteroids alone.
PMID- 10191905
TI - [Management of prolonged fever in infants].
AB - Prolonged fever is defined as an unexplained fever of more than 5 days duration.
In infancy and early childhood, it is most often of infectious origin, viral
infections being the most frequent. Mycoplasma pneumoniae infections, urinary
tract infection and otitis media are also commonly involved. Kawasaki disease is
the main inflammatory etiology, juvenile rhumatoid arthritis in its systemic form
(Still's disease) being much rarer. In most cases the etiological diagnosis can
be made with a limited number of laboratory and/or imaging investigations based
upon a careful clinical evaluation and an oriented chronological strategy.
PMID- 10191906
TI - [Transitory biliary pseudolithiasis appearing quickly after ceftriaxone
treatment].
PMID- 10191907
TI - [Familial hemolytic and uremic syndrome].
PMID- 10191908
TI - [Salmonella enteritidis gastroenteritis and erythema nodosum].
PMID- 10191909
TI - [Dangerous effects of nifluril during pregnancy: a case of chronic renal
insufficiency beginning in the prenatal period].
PMID- 10191910
TI - [Kawasaki disease: diagnostic difficulties and therapeutic indications in the
young infant].
PMID- 10191911
TI - [Pulmonary, splenic, and hepatic hydatidosis in a infant of 23 months].
PMID- 10191912
TI - [Screening of language disorders using the ERTL 4 test].
PMID- 10191913
TI - [Extrapulmonary tuberculosis in children in Abidjan].
PMID- 10191914
TI - [Pediatric AIDS: epidemiological, clinical and prognostic aspects in Abidjan,
Ivory Coast].
PMID- 10191915
TI - [Control of a Serratia marcescens epidemic in neonatology].
PMID- 10191916
TI - [Severe newborn icterus due to Rhesus incompatibility. Treatment with intravenous
immunoglobulins].
PMID- 10191917
TI - [Respiratory allergy in children: current aspects and perspectives].
PMID- 10191918
TI - [Epidemiology of respiratory allergy in children].
AB - Epidemiology of paediatric respiratory allergic disorders allows the approach to
causal and preventive risk factors by studying groups or sub groups of children
in different locations and under different conditions. This is, however,
complicated by the lack of consensus on disease definitions, which renders
comparisons between studies difficult. Atopy is usually defined by the presence
of positive skin tests (wheal size of at least a mean diameter > or = 3 mm), by
the presence of specific IgE, or by the presence of increased total IgE (> or =
100 UI/mL). Infantile asthma is not well defined, complicated by the high
prevalence of bronchiolitis; one thus questions between wheezing or wheezy
bronchitis. Prevalence is high: among early wheezers, two populations will be
defined by the medium term evolution: transient wheezers and persistent wheezers.
Risk factors for these two conditions are different. Childhood asthma may be
defined by the diagnosis of asthma (specific but fairly non-sensitive), by
asthmatic symptoms (wheezing, waking by an attack of shortness of breath)
(sensitive but not very specific), or by the combination of symptoms and airway
hyperresponsiveness. The ISAAC study has standardised a questionnaire to assess
the prevalence of asthma. The preliminary results show that there are wide
variations across the world. The prevalence is low in Africa and Asia,
intermediate in Europe, and high in Anglo-Saxon countries. The prevalence of
asthma has gradually increased over the past 20 years in developed countries.
Asthma and atopy are closely associated in children. Risk factors are genetic,
associated with sex and environmental factors. Among these, allergic
sensitisation is associated with the degree of exposure to allergens.
Westernization of way of life is associated with increased prevalence of atopy,
allergic rhinitis and asthma. Atopy seems inversely correlated to certain
infections. Passive smoking is clearly associated with early wheezing. This and
atmospheric pollution aggravate childhood asthma. However, the inducing role of
pollution on asthma is still controversial.
PMID- 10191919
TI - [Ontogeny of the immune system].
AB - The newborn immune system differs quantitatively and functionally from adults. At
birth, the immune system is partially immature, resulting in deficiency in cell
mediated cytolysis, immunoglobulin synthesis and cytokine production. The most
clearly defined deficit in neonatal phagocytosis defenses is diminished
neutrophil storage. T cell function is diminished, including T cell-mediated
cytotoxicity and T cell help for B cell differentiation. Selective decreases in
cytokine production by T cells may contribute to all of these deficits. One of
the fundamental differences between adults and newborns for T cell functions
resides in whether or not the patient had prior exposure to antigens. Significant
immune responses to antigens can be obtained in the neonatal period. These
responses are qualitatively different from those induced in adults with a
predominance of TH2 pattern.
PMID- 10191920
TI - [Immunological bases and classification of allergy].
AB - The task of the immune system consists of destroying foreign structures in order
to prevent the invasion of living organisms by pathogens. This destruction often
provokes adverse effects defined as hypersensitivity reactions. The
classification of hypersensitivity reactions proposed by Gell and Coombs is based
on effector mechanisms. Although this framework remains largely used, recent work
demonstrated the occurrence of profound similarities between different classes of
hypersensitivity reactions. Indeed, all these reactions involve the activation of
adhesion mechanisms intended to allow the local recruitment of blood leukocytes
and cytokine production. The concept of a separation between two different modes
of immune response induced by two different T lymphocyte subpopulations (TH1 and
TH2) proved useful in understanding hypersensitivity reactions, although it
represents only an approximation. Recent results were an incentive to develop new
diagnostic and therapeutic strategies whose usefulness will be evaluated in the
near future.
PMID- 10191921
TI - [Respiratory allergy and the viruses].
AB - Viral respiratory tract infections are a major cause of wheezing in infants.
Investigators determined that 80% to 85% of school-aged children with wheezing
episodes were tested positive for virus. To more fully understand how viral
respiratory tract infections influence asthma, investigators have evaluated the
effect of respiratory tract infections on airway symptoms, function, and
inflammation. Although the mechanisms by which respiratory viruses enhance lower
airway inflammation are not established, cytokines may play a key role in this
process. The respiratory epithelial cell is a principal host for respiratory
virus replication and is likely to be the first source of cytokines during an
acute infection. T cells orchestrate immune responses to both allergens and
viruses, and regulate effector cells with virucidal and proinflammatory effects.
Although studies demonstrate that virus-specific T cells may contribute to virus
induced lung disease, evidence to define the role of virus-specific T lymphocytes
in asthma has not been fully established. Some infections early in life may also
have an important immunoregulary role in the subsequent development of allergy
and asthma. Atopy is characterised by exaggerated Th-2 cell responses to common
allergens with secretion of cytokines such as IL-4 and IL-5 that promote IgE
production and eosinophil activation. In contrast, childhood infections typically
induce a Th-1 cell response, characterised by secretion of interferon-gamma,
which enhances the antiviral activities of effector cells. These two types of T
cell responses are mutually antagonistic.
PMID- 10191922
TI - [Respiratory allergy in children and passive smoking].
AB - Environmental tobacco smoke interacts with the respiratory mucosa by irritation
and/or inflammation. Environmental tobacco smoke seems also modulate humoral and
cellular immune activity. Thus, environmental tobacco smoke, in all children,
increases the risk of superior and inferior airway infections, modifies the
growth and the natural evolution of the respiratory function, increases the
occurrence of asthma and exacerbates the symptoms of asthma, and creates or
exacerbates a bronchial hyperresponsiveness. In atopic children (defined by the
presence of at least one positive allergy skin test), environmental tobacco smoke
increases the risk of respiratory allergy and exacerbates the symptoms of
respiratory allergy. Parental environmental tobacco smoke is a universal toxic
which must be avoided in both allergic and non-allergic children.
PMID- 10191924
TI - [Allergens causing respiratory allergy: the aeroallergens].
AB - Aeroallergens play a major role in the pathogenesis of allergic diseases,
particularly asthma and rhinitis. Indoor allergens, including house dust mites,
domestic pets, cockroaches, and molds are of particular importance. Pollens are
also recognized as a major source of allergens. The role of these different
allergens varies with environment conditions, such as climatic factors, and
degree of exposure. Knowledge about allergens has progressed, especially with
recent molecular biology studies. Structure and function have been identified.
These studies have provided explanations about the relationship between allergic
sensitization, allergen exposure, and disease activity, about clinical
observations such as allergic cross reactions, and improvement in the production
of allergenic extracts (necessary to diagnosis and immunotherapy). Environmental
control measures are of particular importance in the prevention and management of
allergic diseases.
PMID- 10191923
TI - [Respiratory allergy and environmental pollution in pediatrics].
AB - Allergic disease and pollution effects on children are a subject of worldwide
concern. Outdoor pollution is the sum of acid particle (SO2, NO2, PM) and
photochemical (ozone) pollution. Experimental studies demonstrated correlation
between animals and humans concerning inhalation of pollutants and inflammatory
and functional effects. Several studies among children confirmed with variable
odds ratios the interaction between air pollution and respiratory health, but
other studies showed no clear effect. Physicians should inform parents with
children experiencing respiratory disease.
PMID- 10191925
TI - [Allergy to hymenoptera venoms in children].
AB - Incidence of hymenoptera venom allergy in children is about 0.4 to 0.8%. Clinical
features usually range from urticaria to anaphylaxis. Fatal reactions can occur
but with less frequency than in adults. Allergologic investigations must be
performed in children with systemic or generalized reactions after hymenoptera
stings, which may lead to venom immunotherapy. Venom immunotherapy is well
reported, but protocols differ according to the authors: ultra-rush in 3 h,
accelerated in 3 to 5 days and semi-rush in 2 to 8 weeks. Results are always
excellent (90 to 100%). We report our experience with 91 children receiving venom
immunotherapy. Clinical history and positivity of skin tests indicated
immunotherapy. Clinical symptoms were anaphylaxis (15.3%), serious reaction
(37.3%) strong reaction (34%), and mild reaction (7.6%). Changes in immunological
parameters revealed wide individual variations, not differing from data in the
literature, with no correlation with evolution of immunotherapy. Venom
immunotherapy appeared with good tolerability in children, whatever the protocol
used.
PMID- 10191926
TI - [Food allergens in children].
AB - Food hypersensitivity is increasing, with clinical indications and allergens
multiplying and evolving. We report our experience with clinical indications and
distribution of allergens in children with food hypersensitivity. Data were
established in a prospective study at medical centres in Nancy and Toulouse
(France). We studied 378 children with food hypersensitivity indicated by food
challenge, which account for 74.2% of food hypersensitivity. Clinical features
were: atopic dermatitis (46.5%), urticaria (17.9%), oedema (14.2%), asthma
(8.4%), anaphylaxis (5.2%), gastro-intestinal symptoms (2.1%), oral syndrome
(1.8%) and rhino-conjunctivitis (0.5%). Five allergens accounted for 82% of
confirmed food hypersensitivity: egg (51.8%), peanut (34.3%), milk (11.6%),
mustard (8.9%) and codfish (7.1%). Allergens according to the symptoms showed
that peanut allergies were more serious than other food allergy. Allergens
according to age showed that peanut allergy is the first food allergy occurring
after the age of three. There exists a modification in children's allergen
distribution. Peanut allergy is increasing seriously, and diagnosis with food
challenge is a necessity.
PMID- 10191927
TI - [Respiratory allergy and good clinical practice].
AB - The increase of allergic diseases and asthma requires a rationalization of
diagnostic and therapeutic methods. Medical society guidelines and position
papers attempt an approach to harmonization for good clinical practice in the
field of allergy worldwide, especially immunotherapy.
PMID- 10191928
TI - [Anaphylaxis in children and adolescents: apropos of 44 patients aged 2 months to
15 years].
AB - The increase in frequency of anaphylaxis, an acute allergic reaction which may be
fatal, might be explained by the rise in food allergy. We report a cohort of 44
children, aged 2 months to 15.5 years, who were admitted in a pediatric emergency
unit for serious allergic events. Thirty-two percent, 86% and 66% presented
hypotension, severe edema and respiratory distress, respectively. Three patients
were admitted to the ICU. One-fourth of all children had an angioneurotic edema
history, 1/3 were asthmatics and 41% had known allergy. Etiologies were: food
allergy (42.5%), drugs (14.8%), respiratory allergy (9%), miscellaneous (14.8%),
idiopathic (6.4%) and unknown because of incomplete investigations (12.4%). Three
fourths of food allergies were comprised of the expected protein categories
(milk, nuts, eggs and fish). Nine children had an allergic relapse during the
following months. We otherwise assessed that adrenaline was underused by the
medical staff.
PMID- 10191929
TI - [Acute severe asthma in children. Epidemiological, physiopathological and
clinical aspects].
AB - Therapy for asthma is being prescribed more frequently. However, asthma mortality
remains high in many countries. Fatal outcome is not always related to inadequate
follow-up. In this article we report that children with mild to moderate symptoms
may present a fatal attack. Many factors are responsible for such an outcome:
asphyxia +3 due to ventilation/perfusion mismatch and/or bronchospasm, cardiac
failure, cardiac arrhythmia, intrinsic positive expiratory pressure, or metabolic
disturbances (hypokalemia, for example). Such problems can occur in predisposed
patients: it has been shown that the chemosensitivity to hypoxia and the
perception of dyspnoea are altered in certain patients with near-fatal asthma. It
is very important to identify children at risk of severe asthma and to organize
care so as to optimize the management of such children.
PMID- 10191930
TI - [Extrinsic allergic alveolitis].
AB - Extrinsic allergic alveolitis (EEA) is a lung disease mediated by immunologic
mechanisms and induced by repeated exposure to organic dusts. EAA in children are
mostly observed around 10 years of age. Subacute clinical presentation is the
most frequent. Diagnosis is based on simultaneous presence of most of the
following arguments: exposure to a known risk factor, spontaneous improvement
after cessation of the exposure, identification of specific precipitins,
demonstrative aspects on X-ray and tomodensitometry, and CD8+ lymphocytosis in
bronchoalveolar lavage. Lung biopsy and specific provocation test are rarely
necessary for diagnosis. Treatment is based on total eviction from inhaled
antigen and on oral corticosteroids in acute and subacute forms.
PMID- 10191931
TI - [Allergic bronchopulmonary aspergillosis in children].
AB - Allergic bronchopulmonary aspergillosis (ABPA) associates the development of
aspergillus in bronchus and a predominant immediate hypersensitivity for
aspergillus antigens. It complicates an old and severe allergic asthma or cystic
fibrosis. Its prevalence is not well known. In children, ABPA prevalence is rare,
except in cystic fibrosis where 0.6% to 11% of patients can be affected by the
disease. Acute exacerbation of the disease favours the development of
bronchiectasis and fibrosis. The diagnosis is suggested by an unexplained
aggravation of asthma or, in cystic fibrosis, by wheezing, an unsuccessful
antibiotherapy, and a recent modification of the chest X-ray. The diagnosis is
based upon the presence of seven major criteria or six major criteria and one
minor. The follow-up of biological parameters is important for early diagnosis of
exacerbations. Some parameters are very sensitive, ie, precipitins and total
serum IgE. Systemic corticotherapy is the usual treatment of exacerbation. The
association with inhaled corticotherapy could reduce the duration of systemic
treatment. The use of Itraconazole is logical, mainly in cystic fibrosis.
PMID- 10191932
TI - [Habitat of the allergic child: theory and practice].
AB - Control of the asthmatic child's environment forms an integral part of
therapeutic care. This requires knowing what the main allergens in the child's
habitat are and how they arise: eg, acarids, animal teguments, insects and fungi.
The overall measures for reducing them chiefly entail controlling humidity:
regular airing, or even ventilation, and eliminating sources of humidity can be
recommended. Control of acarids will require modifying furnishings (no mats or
carpeting, non hangings or heavy curtains, a slatted not interior spring bed
base). Acarid-repellent loose covers seem to be more effective than acaricides,
which give conflicting results. Physical processes, although necessary, are
seldom sufficient. Animals should be evicted. If this is impossible, certain
measures have proved effective, however. Insects and moulds are controlled by
specific sanitary measures. A practical approach is proposed that takes into
account both theoretical demands and everyday realities.
PMID- 10191934
TI - [Corticoids and allergy].
AB - Inflammation is constantly observed in allergic reactions. Corticosteroids are
most effective in preventing the late phase of allergic reaction. The action of
glucocorticosteroids is mediated through glucocorticoid receptors present in the
cellular cytoplasm. When activated, glucocorticoid receptors form a dimer and
bind to DNA after migration into the nucleus. Interaction to DNA induces changes
in the transcription rate, leading to either gene induction or gene repression.
Glucocorticoid receptors are also able to interact with transcriptional factors
such as AP-1 (activator protein-1) of NF-kappa B (nuclear factor-kappa B).
Through these actions glucocorticosteroids are susceptible to modify functions of
cells involved in the allergic inflammatory response. They are in particular able
to inhibit most of the pro-inflammatory functions of the eosinophils.
PMID- 10191933
TI - [Antiallergy drugs and respiratory diseases in children].
AB - Second generation antihistamines (anti H1) are effective for seasonal and
perennial rhinoconjunctivitis curative or preventive treatment in children. They
are better tolerated than first generation drugs. They probably do not act
specifically against asthma itself, but are nevertheless useful for relief of
nasal obstruction, which is an asthmogenic factor frequently linked with
bronchial asthma. The therapeutic relevance of oral ketotifen and inhaled
chromones (sodium cromoglycate, nedocromil sodium) is unequally considered among
pediatricians. However, their efficacy has been clearly demonstrated as a ground
treatment in mild-to-moderate asthmatic children. Chromones are also useful in
preventing exercise-induced asthma. Because of their low cost and the lack of
potential side effects, and according to the guidelines established in 1997 by
the National Heart, Lung and Blood Institute, they should be prescribed at first
sight in these indications.
PMID- 10191935
TI - [Specific immunotherapy].
AB - Increase of the prevalence of allergy these last 20 years is in part secondary to
the modification of the allergenic charge of our environment. The specific
immunotherapy (SIT) is the only etiologic treatment of the allergic disease and
numbers of authors believe that, for the future, this treatment could change the
natural history of the respiratory allergy, provided that it is realised early in
the first years of life. Several experimental studies show that the process of
the SIT could be the restoration of the Th1 cell/Th2 cell balance which is
reversed in allergies. However, indications of SIT have to be carefully selected.
The ideal indication is the single sensitized asthma, and treatment has to be
started in the first years of life, at the onset of the asthmatic disease, before
a definitive remodelling of the respiratory airways induced by inflammation.
Subcutaneous SIT is for the moment the only effective route confirmed by several
controlled trials, in particular for grass pollens, possibly for house dust, pet
danders and mite allergens. Risk of syndromic effects, present all the time of
the SIT protocol, can be prevented by rigorous use of the SIT according to the
European consensus. The advent of recombinant allergens, in particular by
complementary DNA (cDNA) modified by site-directed mutagenesis, could tip the
immune response to a Th-1 like response instead of a Th-2 like response (IgE
mediated) and result in a better tolerated and more efficacy immunomodulation.
PMID- 10191936
TI - Aminoglycoside antibiotics--two decades of their HPLC bioanalysis.
AB - Several reviews have been published on high-performance liquid chromatographic
(HPLC) methods for the determination of aminoglycoside antibiotics
(aminoglycosides) in biological fluids [e.g. Nilsson-Ehle, I. (1983). J. Liq.
Chromat. 6: 251]. Of these, the paper by Maitra et al. [(1979a). Clin. Chem. 25:
1361.] briefly summarizes the early 2-3 years of experience on HPLC assaying of
amikacin, gentamicin, netilmicin and tobramycin in body fluids. The reviews by
Nilsson-Ehle, I. [(1983). J. Liq. Chromat. 6: 251] and by Miner, D. J. [(1985).
Antibiotics. In Therapeutic Drug Monitoring and Toxicology by Liquid
Chromatography, (Wong S. H. Y., ed.), ch. 10, p. 269. Marcel Dekker, New York and
Basel.] devoted to the monitoring of antibiotics, also evaluated the first 6-8
years of the application of HPLC assays for the aminoglycosides amikacin,
gentamicin, netilmicin, sisomicin and tobramycin. This report presents a great
majority of the HPLC assay methods published during the last two decades for
determining practically a dozen different aminoglycoside antibiotics in body
fluids, particularly in the serum or plasma, and in urine.
PMID- 10191937
TI - Study on the isolation, purification and physicochemical properties of
polysaccharides from Indocalamus tesselatus.
AB - Polysaccharides prepared from Chinese traditional medicine "Ruoye" (Indocalamus
tesselatus), a kind of bamboo leaves, were studied. Eight crude polysaccharides
were isolated from the dried leaves by successive extraction with 85% ethanol
(FE), 0.9% sodium chloride (FS), hot water (FI), 1% ammonium oxalate (FII), 5%
NaOH (FIII-a, FIII-b) and 20% NaOH (FIV-a, FIV-b). They were decolorized by
hydrogen peroxide treatment and the protein was removed with Savag's method. The
polysaccharides were precipitated by three volumes of absolute ethanol. After
further purification by gel filtration chromatography on a Sephadex G-200 column,
these polysaccharides were lyophilized. Their physicochemical properties and
structural feature were elucidated by modern analytical technique such as UV,
elemental analysis and high performance gel permeation chromatography. From the
results of partial hydrolysis, FE and FIII-b have a main chain comprised solely
of glucuronic acid and xylose residues, respectively.
PMID- 10191938
TI - Development and clinical application of high performance liquid chromatography
for the simultaneous determination of plasma levels of theophylline and its
metabolites without interference from caffeine.
AB - A high performance liquid chromatography (HPLC) method has been developed for the
simultaneous determination of plasma levels of theophylline and its metabolites
without interference from caffeine or caffeine metabolites. The method is simple
and of practical use because it is applicable even to plasma samples from
patients who take caffeine-containing beverages. The method was also reproducible
with a coefficient of variation of less than 5% for each analyte. The levels of
theophylline, determined by HPLC, were validated by their high correlation to the
levels obtained by fluorescence polarization immunoassay. HPLC was used to
determine theophylline levels in patients with bronchial asthma. The data
revealed that the ratio of 1,3-dimethyluric acid, the major metabolite of
theophylline, to theophylline concentration in the plasma was within a narrow
range in most patients (0.055 +/- 0.01, n = 66), regardless of the method of
theophylline administration or the time of blood sampling. Conversely, this ratio
was as low as 0.027 +/- 0.005 in the patient with a long plasma half-life of
theophylline. These results suggest that it may be possible to predict the plasma
half-life of theophylline for each patient from a single blood sample. This may
be useful when planning theophylline administration, especially in patients with
abnormal theophylline metabolism.
PMID- 10191939
TI - Capillary GC-MS determination of melatonin in several pharmaceutical tablet
formulations.
AB - A simple capillary GC-MS method for the determination of melatonin from tablets
is proposed. Melatonin (N-acetyl-5-methoxytryptamine) was determined by gas
chromatography-mass spectrometry after extraction from ground tablets with ethyl
acetate and derivatization with N-methyl-N-trimethylsilyl-heptafluorobutyramide
(MTSHFBA). Splitless injection offers good reproducibility with a standard
deviation of +/- 2%. The proposed method was applied to analyse the melatonin
content from three different tablet formulations.
PMID- 10191940
TI - Changes of plasma L-arginine levels in spontaneously hypertensive rats under
induced hypotension.
AB - Nicardipine, a dihydropyridine type calcium channel blocker, was infused at two
flow-rates into spontaneously hypertensive (SH) and control normotensive Wistar
Kyoto (WKY) rats (young, 6-week-old and adult, 23-week-old, n = 5) under
pentobarbital anesthesia, to cause hypotension. Mean arterial blood pressure and
the concentrations of plasma amino acids and norepinephrine (NE) were measured
before infusion and at each step of the infusion. The reduction in blood pressure
caused by nicardipine induced a decrease in plasma L-arginine concentration in
both young and adult SH rats, this effect being larger in adult rats. There was
no significant change in plasma levels of L-arginine in age-matched WKY rats. The
concentration of other amino acids did not change in both rat strains. On the
contrary, there was an increase in plasma NE concentration in both SH and WKY
rats after infusion with nicardipine. Plasma L-arginine concentration showed a
good inverse correlation with the logarithm of plasma NE concentration in SH and
WKY rats and the correlation was expressed as Y = -alpha log(X) + m (Y, plasma L
arginine concentration (nmol/mL); X, plasma NE concentration (pmol/mL); alpha, a
slope; and m, an intercept). alpha, 43.0 and 4.35 for 23-week-old SH and WKY
rats, respectively, and 17.0 and 4.0 for 6-week-old SH and WKY rats,
respectively. The present data together with previous data suggest a direct
noradrenergic stimulation of the synthesis of nitric oxide (NO) from L-arginine.
The findings also indicate an impairment of the L-arginine metabolism or pools in
SH rats compared with WKY rats. The deficiency of L-arginine increases with the
age of SH rats and could be related to the development and maintenance of
hypertension due to inefficient production of NO.
PMID- 10191941
TI - Chiral gas chromatographic assay with flame ionization detection for amphetamine
enantiomers in microsomal incubates.
AB - A chiral assay for amphetamine enantiomers in rat liver microsomal incubates is
based on derivatization with (S)-(-)-N-(trifluoroacetyl)-prolyl chloride (S
TFPC), capillary chromatographic separation of the diastereomeric amide
derivatives, and detection by a flame ionization detector. The method is capable
of detecting low levels of S- or R-amphetamine. The assay is linear from 5 to 250
micrograms/mL for each enantiomer, and the limit of detection is 0.5
microgram/mL. The analytical method affords the average recoveries of 77.53 +/-
5.22% for R-amphetamine and 74.47 +/- 3.08% for S-amphetamine. The method allows
the study of the metabolic depletion of S- and R-amphetamine in rat liver
microsomal incubates. The time-dependent concentration of amphetamine enantiomers
in rat liver microsomes was determined, and the stereoselectivity of amphetamine
phase I metabolism was observed.
PMID- 10191942
TI - On-line sample clean-up and chromatography coupled with electrospray ionization
mass spectrometry to characterize the primary sequence and disulfide bond content
of recombinant calcium binding proteins.
AB - We have used on-line sample clean-up, concentration, and chromatography with
electrospray ionization mass spectrometry (ESI-MS), to characterize and determine
the presence of disulfide bonds in recombinant full-length rat brain calbindin
D28K and two deletion mutants of the protein, one lacking EF-hand 2 (calbindin
delta 2) and the other lacking EF-hands 2 and 6 (calbindin delta 2,6). The
molecular weights of the expressed proteins dissolved in biological buffers were
determined with high accuracy using a low-flow, pressurized chamber infusion
system, that allows on-line protein clean-up by removing buffers/salts
incompatible with ESI-MS. The molecular weight determinations showed that the
amino-terminal methionine residues had been cleaved during the expression and
isolation of the recombinant proteins. Approximately 85-90% of the protein
sequences were confirmed by on-line HPLC-ESI-MS analysis of peptides generated by
a lysyl endoproteinase C digestion. Comparisons of ESI-MS spectra of native and
reduced calbindin D28K and delta 2 show that the full length- and delta 2 mutant
protein contain one disulfide bond. Molecular mass determinations of calbindin
delta 2,6 showed that this protein contains a highly active cysteine residue that
covalently binds a mercaptoethanol group, or forms a homodimer via a disulfide
bond. The results show surprising differences amongst the deletion mutants of
calbindin D28K with respect to the formation of disulfide bonds. These
differences are not readily detected by other techniques and show that ESI-MS is
a powerful, rapid method by which to detect disulfide linkages for intact
proteins.
PMID- 10191943
TI - GC-MS analysis of diaminopimelic acid stereoisomers and amino acid enantiomers in
rumen bacteria.
AB - The amounts and the configuration of the stereoisomers of 2,6-diaminopimelic acid
(Dap) and the enantiomeric content of other amino acids were determined in five
individual species (Fibrobacter succinogenes, Streptococcus bovis, Selenomonas
ruminantium, Prevotella ruminicola and Anaerovibrio lipolytica) of rumen
bacteria, and in samples of mixed rumen bacteria isolated from sheep. The
separation and quantification of the Dap stereoisomers was achieved by gas
chromatography (GC) of trifluoroacetyl 2-propyl esters on a Chirasil-L-Val fused
silica column, and detection was achieved by selected ion monitoring mass
spectrometry (SIM-MS). No isomers of Dap were detected in S. bovis and P.
ruminicola, two of the bacterial isolates. LL- and DD-Dap were not detected in
any of the bacterial samples. As only the meso-isomer of Dap was detected in
these microorganisms, it was quantified by adding LL-Dap as an internal standard
before the bacteria were acid-hydrolyzed. Amounts of between 4.8 and 12.0 mg meso
Dap per gram of bacterial dry matter (DM) were determined. The presence in the
rumen bacteria of free amino acid enantiomers, extractable with 70% aqueous
ethanol, were determined by GC-SIM-MS; the D-amino acids were predominantly Ala,
Asp and Glu, but there was considerable variation between the species.
PMID- 10191944
TI - Direct injection HPLC analysis of some non-steroidal anti-inflammatory drugs on
restricted access media columns.
AB - Direct serum injection methods are described for the HPLC determination of
selected non-steroidal anti-inflammatory drugs (NSAIDS) on restricted access
media (RAM) columns, using either a Pinkerton (ISRP) or semi-permeable surface
(SPS) column. Twenty microlitres of a filtered serum sample was injected directly
onto each column. Calibration curves were prepared for ketoprofen (1-20
micrograms/mL), fenbufen (0.8-20 micrograms/mL), sulindac (0.8-20 micrograms/mL)
and probenecid (1.5-40 micrograms/mL) on the SPS column, and nabumetone (1.5-40
micrograms/mL) and indomethacin (1.5-40 micrograms/mL) on the Pinkerton column.
The percentage error and imprecision of the methods were found to be less than
10%. The inter- and intra-day variability for analytes were in the range of 0.15
10%. The limits of quantitation and detection were in the range of 800-1500 and
300-800 ng/mL, respectively, for the analytes studied. A hydrophobic shielded
phase (Hisep) column was also investigated and was found to be generally too
retentive (> 29 min) for assay of these analytes.
PMID- 10191945
TI - Analysis of N-acetyl and N-glycolylneuraminic acid in rat serum and tissues with
Walker 256 carcinoma by high-performance liquid chromatography.
AB - Serum and tissue specimens from healthy Wistar rats and from rats with Walker 256
carcinoma were analysed for N-acetyl and N-glycolylneuraminic acid by high
performance liquid chromatography (HPLC) as per-O-benzoylated derivatives. Both
neuraminic acids were identified, while N-acetylneuraminic acid was the
predominant sialic acid. Samples from rats with generalized metastasis showed a
significant increase (45-80%) of total sialic acids. This phenomenon in serum is
caused by the overproduction of sialic acids, as a result of synthesis of both
types of neuraminic acids to a similar molar ratio. The increase of sialic acids
in rat bones with metastatic cancer is mainly because of increased N
acetylneuraminic acid synthesis. These results suggest that the molecular
mechanisms responsible for cancer metastasis in different tissues may be closely
associated with increased synthesis of dominating neuraminic acid.
PMID- 10191946
TI - Direct injection of plasma to determine pseudoephedrine by high performance
liquid chromatography with column switching.
AB - An HPLC method has been developed for the determination of pseudoephedrine in
plasma using column switching. Preparation of the sample was simple in that only
1000 microL of water was added to 200 microL of plasma before injection. A 900
microL aliquot was injected onto the precolumn. Double distilled water was used
to elute and remove proteins and polar components in the sample. The components
retained on the precolumn were flushed forward onto the analytical column by the
mobile phase (acetonitrile-0.2 mol/L ammonium sulphate, 10:90 v/v) with automated
column switching. The limit of determination of pseudoephedrine in plasma was 12
ng/mL. The relative standard deviations of intra- and inter-assay for the
determination of pseudoephedrine in plasma were 1.2-9.8% over the concentration
range 1020-21.8 ng/mL. The mean recovery by on-line solid phase extraction was
94.76% (RSD = 1.1%).
PMID- 10191947
TI - Buffer effect on the kinetics of ornithine carbamyl transferase by HPLC.
AB - A kinetic study of ornithine carbamyl transferase (OCT) from Streptococcus
faecalis has been carried out, employing a new HPLC method based on the direct
determination of citrulline. A different kinetic pattern was observed in
tris(hydroxymethyl)-aminomethane (TRIS) and triethanolamine (TEA) buffers: a ping
pong or an ordered sequential mechanism are suggested, respectively. The
inhibition of Tris buffer on OCT reaction has also been demonstrated. The
inhibition of Tris buffer on OCT reaction has also been demonstrated.
PMID- 10191948
TI - Ion exchange chromatography of aluminum using 3-carboxy-2-naphthylamine-N,N
diacetic acid as a fluorescent post-column chelating reagent.
AB - Ion exchange chromatography of aluminum ion using 3-carboxy-2-naphthylamine-N,N
diacetic acid (CNDA) as a fluorescent post-column chelating reagent was studied.
The solution containing ammonium chloride and hydrochloric acid was used for the
eluent, and acetate buffer solution containing CNDA was used for the post column
chelating reagent. The peak of aluminum was separated from that of calcium,
magnesium and zinc, and the chromatogram was not affected by copper(II) and
iron(III). The calibration curve gave linear plots with a range of 0.0027-0.54
ppm aluminum, the regression coefficient of correlation (r2) was 1.000, and the
detection limit (S/N = 3) was 0.3 ppb, indicating that the method could determine
aluminum with high sensitivity. It was demonstrated that CNDA is a useful
metallofluorescent reagent for aluminum. This method has been successfully
applied to the determination of aluminum in some tea drinks.
PMID- 10191949
TI - Determination of 4-hydroxy-2-nonenal in primary rat hepatocyte cultures by liquid
chromatography with laser induced fluorescence detection.
AB - An HPLC (high performance liquid chromatography) method with laser induced
fluorescence (LIF) detection is described for the determination of 4-hydroxy-2
nonenal (HNE) formed from lipid peroxidation in rat hepatocytes. Carbonyl
compounds were fluorescently labelled by incubating the hepatocyte samples with a
tagging reagent, 4-(2-carbazoylpyrrolidin-1-yl)-7-nitro-2,1,3-benzoxadiazole (NBD
ProCZ), at 60 degrees C for 10 min. The hydrazone derivatives were extracted with
a C18 solid phase extraction (SPE) cartridge and separated on a reversed-phase
HPLC column. The detection limit was 2.5 fmol or 0.5 nM (5 microL injection) of
HNE in the cell homogenate. Method precision (C.V.) was 5% at the 5 nM level. The
method has been used to determine free HNE in rat hepatocyte samples treated with
several pro-oxidant toxins. A significant HNE increase (from 4 to 27.6 pmol/10(6)
cells) was observed with the samples treated by allyl alcohol. The results were
in accordance with those for malondialdehyde formation as measured by a
thiobarbituric acid (TBA) assay.
PMID- 10191950
TI - Plasma total homocysteine measurement by ion-paired reversed-phase HPLC with
electrochemical detection.
AB - Homocysteine is thought to be a risk factor for vascular disease and this has led
to an increase in demand for its assay in clinical laboratories. An HPLC method,
incorporating electrochemical detection, for measurement of plasma total
homocysteine is presented. The method is simple to perform, precise and suitable
for clinical applications.
PMID- 10191951
TI - Studies on the determination of diacetyl guanfubase A concentration in rabbit
plasma and pharmacokinetics.
AB - A gas chromatographic method for monitoring diacetyl guanfubase A in plasma is
described. The procedure involved a single solvent extraction of drug from rabbit
plasma into ethyl acetate with guanfubase A as an internal standard. The extract
was analyzed subsequently on a gas chromatograph equipped with a hydrogen flame
ionization detector. The recovery was 86.43% +/- 6.90% (+/- SD); the RSD of
within-day and between-day was 2.81%-5.26% and 5.22%-8.24%, respectively; the
regression line was linear over the concentration range of 25-200 micrograms/mL,
the limit of detection was 10 micrograms/mL. No endogeneous interference was
found in chromatograms of the biological samples. This method was applied to the
pharmacokinetic study of diacetyl guanfubase A in rabbits.
PMID- 10191952
TI - Development of an HPLC method for determining the alpha 2-adrenergic receptor
agonist brimonidine in blood serum and aqueous humor of the eye.
AB - A procedure for determining brimonidine [5-bromo-6-(2-imidazolidinylideneamino)
quinoxaline] in biological samples using a reversed-phase isocratic HPLC method
is described. The application in blood serum and eye aqueous humor of patients
treated with the Alphagan ophthalmic solution was carried out by enrichment of
samples in brimonidine with solid-phase liquid extraction. Brimonidine reached
maximum levels in aqueous humor and serum within 2-2.5 h, whereafter a declining
pattern was obtained. An approximate 50% level of brimonidine was identified in
serum at 12 h after ocular administration, whereas in aqueous humor this
percentage was determined after a period of 4-5 h.
PMID- 10191953
TI - Determination of ferrocene-A in the blood serum of rabbits using reversed-phase
microcolumn HPLC.
AB - Ferrocene-A (ferrocenyl-1-phenyl-1-dioxy-1,4-butin-2) has shown significant
antitumour and antibacterial activity. To facilitate studies in this field a
simple and rapid liquid chromatographic procedure was developed, allowing the
determination of ferrocene-A in the blood serum. The procedure was based on a
reversed-phase high-performance liquid chromatography (HPLC) method, with UV
detection at 210 nm. The mobile phase ethanol-0.01 M KH2PO4 60:40 (v/v) provides
the complete separation of ferrocene-A, internal standard and endogenous
compounds of serum. The recovery of ferrocene-A from serum using a hexaneisoamyl
alcohol mixture was 90%. The proposed method is convenient for pharmacological
and pharmacokinetic applications.
PMID- 10191954
TI - Fiber optic Z-cell for CZE.
AB - Fiber optic Z-cell for CZE was designed, constructed, tested and compared with on
column detection. Ten times higher sensitivity for Z-cell in comparison with on
column detection was achieved as expected from optical pathlength ratio. Linear
dynamic range was > 4 orders of magnitude for both cells.
PMID- 10191955
TI - Characterization of a dextran-based bifunctional calcium indicator immobilized in
cells by the enzymatic addition of isoprenoid lipids.
AB - Cellular processes can be controlled by cell-wide increases in the cytosolic Ca2+
concentration or, alternatively, by localized Ca2+ signals in micro- and nano
domains. The experimental characterization of such localized Ca2+ signals would
be facilitated using an immobilized Ca2+ indicator, which could prevent the
accelerated spatial spreading of Ca2+ ions that is mediated by binding to
diffusible indicators. Here we characterize a dextran-based Ca2+ indicator (CAAX
green) that becomes immobilized in the cytosol by an enzyme-mediated addition of
a geranylgeranyl lipid group. CAAX-green consists of a dextran backbone with an
attached Ca(2+)-green as well as an 11 residue peptide ending in a C-terminal
CAAX-motif. Once introduced into cells by microporation, geranylgeranyl lipid
groups are attached to the CAAX peptides by cytosolic enzymes. Measurements in
tumor mastcells, myocytes and fibroblasts showed that the indicator becomes
membrane attached between 30 min and 1 h following incorporation into the
cytoplasm. A time-dependent 10-fold reduction of the diffusion coefficient and a
parallel increase in the cytosolic retention after permeabilization indicates
that at least 90% of cellular CAAX-green is immobilized. The KD of the indicator
in permeabilized cells is 0.65 microM. Overall, these properties make CAAX-green
well suited for the investigation of localized Ca2+ signals in a variety of cell
types.
PMID- 10191956
TI - Functional expression of the human cardiac Na+/Ca2+ exchanger in Sf9 cells: rapid
and specific Ni2+ transport.
AB - Although inhibition of the Na+/Ca2+ exchanger normally increases [Ca2+]i in
neonatal cardiac myocytes, application of the inhibitor Ni2+ appears to reduce
[Ca2+] measured by fluo-3. To investigate how the apparent reduction in [Ca2+]i
occurs we examined Ca2+ transport by the human Na+/Ca2+ exchanger expressed in
Sf9 cells. Transport of Ca2+ by the Na+/Ca2+ exchanger was examined using a laser
scanning confocal microscope and the fluorescent Ca2+ indicator fluo-3, and the
electrogenic function was determined by measuring the Na+/Ca2+ exchange current
(INaCa) using patch clamp methods. INaCa was elicited with voltage-clamp steps or
flash photolysis of caged Ca2+. We show significant expression of Na+/Ca2+
exchanger function in Sf9 cells infected with a recombinant Baculovirus carrying
the Na+/Ca2+ exchanger. In addition to measurements of INaCa, characterization
includes Ca2+ transport via the Na+/Ca2+ exchanger and the voltage dependence of
Ca2+ transport. Application of Ni2+ blocked INaCa but, contrary to expectation,
decreased fluo-3 fluorescence. Experiments with infected Sf9 cells suggested that
Ni2+ was transported via the Na+/Ca2+ exchanger at a rate comparable to the Ca2+
transport. Once inside the cells, Ni2+ reduced fluorescence, presumably by
quenching fluo-3. We conclude that Ni2+ does indeed block INaCa, but is also
rapidly translocated across the cell membrane by the Na+/Ca2+ exchanger itself,
most likely via an electroneutral partial reaction of the exchange cycle.
PMID- 10191957
TI - Assessment and validation of a microinjection method for kinetic analysis of
[Ca2+]i in individual cells undergoing apoptosis.
AB - Normal and malignant epithelial cells are induced to undergo apoptosis by a large
variety of mechanistically diverse agents. Regardless of inducing agent,
apoptosis characteristically occurs asynchronously within a population of
epithelial cells over a period of 12-96 h and is associated with permeability and
enzymatic perturbations. Pre-loading of cells with acetoxymethyl esters (AM)
derivatives of fluorescent Ca2+ indicators (i.e. fura-2, indo-1, fluo-3) by
passive diffusion allows longitudinal kinetic analysis of acute [Ca2+] changes
subsequent to exposure to apoptosis inducing agents. Using prostate cancer cell
lines, however, it is demonstrated that dye leakage and compartmentalization into
organelles limit such passive loading to longitudinal [Ca2+]i measurements of < 2
h. Post-loading of cells exposed to the apoptosis inducing agent for several
hours is also inaccurate owing to decreased loading efficiency and de
esterification of the probes resulting in increased production of fluorescent
Ca(2+)-insensitive dye species. To accurately measure kinetics of [Ca2+]i changes
longitudinally in individual cells undergoing apoptosis, cells were microinjected
with fura dextran and maintained in a physiologic environment. [Ca2+] and
morphological changes characteristic of apoptosis were then followed
simultaneously in individual cells over several days following exposure to the
apoptosis inducing agent.
PMID- 10191958
TI - Clearance of large Ca2+ loads in a single smooth muscle cell: examination of the
role of mitochondrial Ca2+ uptake and intracellular pH.
AB - Redistribution of cytosolic free Ca2+ following Ca2+ influx into the cytoplasm
was studied in single smooth muscle cells isolated from guinea-pig urinary
bladder. Voltage-clamped cells were loaded with a low-affinity fluorophore Indo
1FF. A decay of free intracellular Ca2+ ([Ca2+]i) after the termination of the
depolarizing pulse (1 s from -50 mV to +20 mV) was fitted with a single
exponential and the effect of various substances on the time constant was
compared. At a holding potential of +80 mV the [Ca2+]i decay was 1.56 times
slower compared to that at -50 mV suggesting the presence of a voltage-dependent
process redistributing Ca2+. In the presence of cyclopiazonic acid (CPA, 10
microM), an inhibitor of sarco(endo)plasmatic Ca2+ pump (SERCa), the [Ca2+]i
decay was 3.93 times slower than that in the absence of the inhibitor.
Introduction of a polycation Ruthenium Red (RR) (20 microM), an inhibitor of the
mitochondrial Ca2+ uniporter, into a cell or collapsing a transmitochondrial H+
gradient with the protonophore CCCP (2 microM) slowed down the [Ca2+]i decay 6.05
fold and 9.78-fold, respectively. The apparent amplitude of [Ca2+]i increments
was also increased by CCCP. Increasing H+ buffering power in the intracellular
solution from 10 mM to 40 mM of HEPES greatly reduced the effect of CCCP on
[Ca2+]i decay. A further increase in HEPES concentration to 100 mM eliminated the
effects of CCCP both on the time course of [Ca2+]i decay and on the amplitude of
[Ca2+]i increment. Perfusion of RR together with 100 mM HEPES into the cytoplasm
was without effect on the decay time course of [Ca2+]i. The effect of CPA on
[Ca2+]i decay was also reduced in cells loaded with 100 mM HEPES; the time
constant in the presence of CPA was slowed down by a factor of 2.18. Application
of 10 mM Na(+)-butyrate to the cells loaded with 10 mM HEPES resulted in a
slowing down of [Ca2+]i decay: the time constant was increased by a factor of
5.84. Measurement of intracellular pH with SNARF-1 confirmed cytoplasmic
acidification during application of Na(+)-butyrate and CCCP. It is concluded that
the contribution of mitochondrial Ca2+ uptake to the rapid [Ca2+]i decay is much
less than could be extrapolated from action of protonophores in these smooth
muscle cells. The results also demonstrate the importance of intracellular pH for
Ca2+ handling in the cytoplasm of smooth muscle cells.
PMID- 10191959
TI - Calcium dependence of Donnan potentials in rigor: the effects of [Mg2+] and
anions in isolated rabbit psoas muscle fibres.
AB - Contraction in vertebrate striated muscle is known to be dependent upon the
binding of calcium ions to the regulatory protein troponin C (TnC). Our
electrical (Donnan potential) studies of the subsarcomeric regions have revealed
an electrical switching mechanism, which is sensitive to both cation
concentration and to particular anions. In a buffer containing phosphate and
chloride ions and at 2.7 mM Mg2+ we observe a single charge transition at pCa50
6.8 in both A- and I-bands. At zero Mg2+ the pCa50 of the A-band transition is
shifted to 8.0 and the I-band shows two transitions (pCa50 approximately 6.8 and
approximately 8.2). Increasing [Mg2+] to 4.5 mM produces a complex effect between
pCas 7 and 9 in both bands. All effects are abolished at 9 mM Mg2+. In a chloride
only buffer (imidazole) at zero Mg2+ the direction of the charge transitions is
reversed. In addition, two transitions (pCa50 approximately 8.5 and approximately
7.0) are evident in the A-band and three in the I-band (pCa50 approximately 8.5,
approximately 7.4, approximately 6.7). In the presence of Mg2+, again the effects
of pCa upon the Donnan potential are complex. In the A-band at 2.7 mM Mg2+ two
transitions of opposite sign predominate (pCa approximately 7 and approximately
8), whilst in the I band a single transition (pCa approximately 8.3) occurs in
the same direction as that observed in phosphate buffer. At 4.5 mM Mg2+ the 'W'
shape observed in the corresponding phosphate buffer is preserved in both bands
with similar pCa50s. This shape is also apparent in the 9 mM Mg2+ solution. In
these two buffer systems, the magnitude of the charge change in terms of electron
binding is far larger than expected from simple Ca2+/Mg2+ binding to troponin. In
an acetate-only buffer, however, the Donnan potentials of the A-band and I-band
were very similar in magnitude and the charge change across the full pCa curve is
close to the expected value for Ca2+/Mg2+ binding to troponin. We speculate that
titin has a role in the calcium activation of striated muscle in vertebrates for
four reasons. First, the effects of long-term storage of the glycerinated muscle;
second, the action of [Mg2+]ions; third the effect of anions; and fourth, our
published and unpublished observations of sarcomere-length dependence. We also
demonstrate the validity of our methodology, relating the charge transitions that
we observe to cation-binding studies of a more traditional nature.
PMID- 10191960
TI - Tetracaine stimulates insulin secretion from the pancreatic beta-cell by release
of intracellular calcium.
AB - The role of intracellular calcium stores in stimulus-secretion coupling in the
pancreatic beta-cell is largely unknown. We report here that tetracaine
stimulates insulin secretion from collagenase-isolated mouse islets of Langerhans
in the absence of glucose or extracellular calcium. We also found that the
anesthetic evokes a dose-dependent rise of the intracellular free-calcium
concentration ([Ca2+]i) in cultured rat and mouse beta-cells. The tetracaine
specific [Ca2+]i rise also occurs in the absence of glucose, or in beta-cells
depolarized by exposure to a Ca(2+)-deficient medium (< 1 microM) or elevated
[K+]o. Furthermore, tetracaine (> or = 300 microM) depolarized the beta-cell
membrane in mouse pancreatic islets, but inhibited Ca2+ entry through voltage
gated Ca2+ channels in HIT cells, an insulin-secreting cell line. From these data
we conclude that tetracaine-enhancement of insulin release occurs by mechanisms
that are independent of Ca2+ entry across the cell membrane. The tetracaine
induced [Ca2+]i rise in cultured rat beta-cells and insulin secretion from mouse
islets is insensitive to dantrolene (20 microM), a drug that inhibits Ca2+
release evoked by cholinergic agonists in the pancreatic beta-cell, and
thapsigargin (3 microM), a blocker of the endoplasmic reticulum (ER) Ca2+ pump.
We conclude that the Ca2+ required for tetracaine-potentiated insulin secretion
is released from intracellular Ca2+ stores other than the ER. Furthermore,
tetracaine-induced Ca2+ release was unaffected by the mitochondrial electron
transfer inhibitors NaN3 and rotenone. Taken together, these data show that a
calcium source other than the ER and mitochondria can affect beta-cell insulin
secretion.
PMID- 10191961
TI - Genistein inhibits lysosomal enzyme release by suppressing Ca2+ influx in HL-60
granulocytes.
AB - The tyrosine kinase inhibitor genistein (5-200 microM) suppressed Ca(2+)
dependent fMLP (1 microM) and ATP (100 microM)-induced release of the lysosomal
enzyme, beta-glucuronidase from neutrophil-like HL-60 granulocytes. Agonist
induced Ca2+ mobilization resulted from the release of intracellular Ca2+ stores
and the influx of extracellular Ca2+. Genistein (200 microM) suppressed fMLP (1
microM) and ATP (100 microM)-induced Ca2+ mobilization, by 30-40%. Ca2+ release
from intracellular stores was unaffected by genistein, however, genistein
abolished agonist-induced Ca2+ (Mn2+) influx. Consistent with these findings,
genistein (200 microM) or removal of extracellular Ca2+ (EGTA 1 mM), inhibited
Ca(2+)-dependent agonist-induced beta-glucuronidase release by similar extents
(about 50%). In the absence of extracellular Ca2+, genistein had a small
additional inhibitory effect on fMLP and ATP-induced beta-glucuronidase release,
suggesting an additional inhibitory site of action. Genistein also abolished
store-operated (thapsigargin-induced) Ca2+ (Mn2+) influx. Neither fMLP nor ATP
increased the rate of Mn2+ influx induced by thapsigargin (0.5 microM). These
data indicate that agonist-induced Ca2+ influx and store-operated Ca2+ influx
occur via the same genistein-sensitive pathway. Activation of this pathway
supports approximately 50% of lysosomal enzyme release induced by either fMLP or
ATP from HL-60 granulocytes.
PMID- 10191962
TI - Octanol blocks fluid secretion by inhibition of capacitative calcium entry in rat
mandibular salivary acinar cells.
AB - The aliphatic alcohol octanol is thought to modulate enzyme secretion from the
exocrine pancreas by the inhibition of gap junction permeability. We have now
investigated the effects of octanol on salivary secretion and intracellular
calcium concentration ([Ca2+]i), measured in isolated perfused rat mandibular
glands and in isolated mandibular acinar cells respectively. Stimulation of
perfused glands with 10 microM carbachol (CCh) evoked a rapid increase in fluid
secretion followed by a decrease to a sustained elevated level. Application of 1
mM octanol during CCh stimulation inhibited fluid secretion reversibly. In
isolated acini, the CCh-induced [Ca2+]i increase was reversibly inhibited by the
same concentration of octanol. However, octanol also inhibited the increase in
[Ca2+]i in single acinar cells where gap junctions were no longer functional,
indicating that octanol directly affected the intracellular Ca2+ signalling
pathway. The initial increase in [Ca2+]i induced by 0.5-10 microM CCh, which is
due to Ca2+ release from IP3-sensitive Ca2+ stores, was not affected by
pretreatment with octanol. In contrast, CCh-, phenylephrine- or thapsigargin
induced Ca2+ entry was almost completely and reversibly inhibited by octanol.
Octanol also blocked agonist-evoked Ca2+ entry in pancreatic acinar cells, and
thapsigargin-evoked Ca2+ entry in fibroblasts. These data strongly suggest that
octanol blocks salivary secretion from mandibular gland by the inhibition of
capacitative Ca2+ entry, and raise the possibility that octanol may be a useful
tool for inhibiting agonist-evoked Ca2+ entry pathways.
PMID- 10191963
TI - Two-photon and UV-laser flash photolysis of the Ca2+ cage, dimethoxynitrophenyl
EGTA-4.
AB - We report efficient two-photon and UV-laser flash photolysis of
dimethoxynitrophenyl-EGTA-4 (DMNPE-4), a newly-developed photolabile Ca(2+)
specific chelator. This compound exhibits good two-photon absorption at 705 nm,
has a low Mg2+ affinity (approximately 7 mM), a Kd for Ca2+ of 19 nM, a quantum
yield of 0.20 and changes its Ca2+ affinity by 21,000-fold upon photolysis. Two
photon excitation photolysis (TPP) experiments were performed with a Ti:Sapphire
laser in solutions containing DMNPE-4 with either 0 or 10 mM Mg2+ and compared to
that of the widely used Ca2+ cage, DM-nitrophen (Kd for Ca2+ 5 nM, Kd for Mg2+
2.5 microM, quantum yield 0.18, affinity change 600,000-fold). The resulting Ca2+
signals were recorded with the fluorescent Ca2+ indicator fluo-3 and a laser
scanning confocal microscope in the line-scan mode. In vitro, photolysis of DMNPE
4:Ca2+ produced Ca(2+)-release signals that had comparable amplitudes and time
courses in the presence and absence of Mg2+. However, photorelease of Ca2+ from
DM-nitrophen was obviated by the presence of Mg2+. In patch-clamped isolated
cardiac myocytes, equivalent TPP results were obtained in analogous experiments.
Single-photon excitation of DMNPE-4 by Nd:YAG laser flashes produced Na-Ca
exchange currents of comparable amplitude in the absence and presence of Mg2+.
However, only very small currents were observed in DM-nitrophen solution
containing 10 mM Mg2+. In conclusion, both DMNPE-4 and DM-nitrophen undergo TPP,
however, only DMNPE-4 exhibits efficient release of Ca2+ in the presence of Mg2+.
PMID- 10191964
TI - Actual versus actuarial analysis for cardiac valve complications: the problem of
competing risks.
AB - Methods for analyzing rates of events such as heart valve failure following
surgery are important for comparing different techniques and devices; however, in
patients undergoing major surgery, other risks such as mortality compete with the
risk of heart valve failure to determine each patient's final outcome. When
multiple, mutually exclusive endpoints are possible, a situation known to
statisticians as a competing risks problem arises. No single statistical
technique that is currently available provides an entirely satisfactory solution
to this problem. We argue that in order for valve failure incidences to be useful
clinically, the overall patient outcome milieu from which these failures arise
must be considered. In this article, we review recent work in the area of
competing-risks analysis as it pertains to heart valve surgery outcome.
PMID- 10191965
TI - Stentless xenograft aortic valves.
AB - Replacement of the diseased aortic valve represents one of the triumphs of
cardiac surgery; however, the perfect valve substitute continues to elude
surgeons after almost four decades of clinical experience. The characteristics of
the ideal valve substitute include the following: central flow capacity, low
transvalvular gradient, low thrombogenicity, durability, easy availability,
resistance to infection, non-immunogenicity, and easy implantability. The
pulmonary autograft first performed by Ross (Lancet 1967, 2:956-958) came closest
to achieving these goals, but creates a double valve procedure for single valve
disease. Aortic valve replacement (AVR) with homograft aortic valve was
introduced by Ross in 1962 (Lancet 1962, 2:487) and Barratt-Boyes in 1964 (Thorax
1964, 19:131-150). Like the pulmonary autograft, homograft AVR results in an
excellent hemodynamic outcome but suffers from limitations of graft availability,
lack of durability, and difficulty with implantation. Mechanical valves and
stented tissue valves allow "off the shelf" easy availability as well as easy
implantability. These valves are unfortunately intrinsically obstructed to some
extent because of the space occupied by the stent and sewing ring. Stent mounted
tissue valves also continue to exhibit limited durability. Stentless xenograft
aortic valves have been developed as a compromise between these ends of the valve
spectrum to allow excellent hemodynamics and hopefully improved durability while
allowing "off the shelf" availability in a variety of standard sizes. We examine
the rationale for use of the stentless xenograft aortic valve, the clinical
development of this valve, and the surgical techniques of implantation.
PMID- 10191966
TI - Acceptance and versatility of the Ross procedure.
AB - During the 31 years since the initial Ross procedure, data have been collected
that have been helpful in assessing long-term performance of the autograft. The
ongoing study of the pulmonary autograft supports the use of the Ross procedure
in young patients, in females of childbearing age, and in patients with
congenital aortic stenosis and complex left ventricular outflow tract
obstruction. We continue to see little or no thromboembolism despite no
anticoagulation therapy. The remarkable ability of the autograft to grow in
children is extremely beneficial. Additionally, excellent results have been
obtained in some series for the treatment of endocarditis. Recently, the
autograft has performed similarly to a normal aortic valve under high stress.
Changes in implantation techniques transitioning from subcoronary to root
replacement and performing annular narrowing has decreased the incidence of early
regurgitation. A potential for an immune response with resulting pulmonary
stenosis and possible early explanation of the pulmonary homograft exists;
however, overall, results of the Ross procedure are excellent and highly
reproducible.
PMID- 10191967
TI - Balloon valvuloplasty for mitral stenosis.
AB - Balloon mitral valvuloplasty (BMV) for mitral stenosis is a procedure that has
evolved significantly since its introduction by Inoue et al. in 1984. This
article reviews currently used techniques, advantages, and limitations as well as
outcomes in comparison with surgical procedures. Included is a review of imaging
techniques that facilitate BMV, such as transesophageal echocardiography and the
recently developed tri-dimensional transthoracic echocardiography and
intracardiac echocardiography. In a separate section, the application of BMV in
specific clinical situations, such as in patients with multivalvular disease,
during pregnancy, in children, in the presence of thrombi, and in patients with
bioprostheses, is discussed.
PMID- 10191969
TI - The role of exercise-based prognosticating algorithms in the selection of
patients for heart transplantation.
AB - The selection of patients for heart transplantation involves the use of multiple
prognostic variables. Because of the complexity of the clinical syndrome of heart
failure, central cardiac and peripheral maladaptations occur. Exercise capacity
simultaneously assesses cardiovascular reserve and evaluates the peripheral
maladaptations; accordingly, exercise testing has become an increasingly
important tool in the risk stratification of these patients. Established
prognostic indicators in heart failure are reviewed. The role exercise testing
plays in selecting ambulatory patients for heart transplantation is emphasized.
PMID- 10191968
TI - Mitral valve replacement with preservation of the subvalvular apparatus.
AB - The introduction of the Starr-Edwards valve allowed complete replacement of
diseased left-sided heart valves. With improved cardiopulmonary bypass,
myocardial protection, and surgical techniques the mortality rate from aortic
valve replacement decreased substantially, whereas the mortality rate from mitral
valve replacement remained high, largely because of low cardiac output syndrome.
Increasing use of mitral valve repair techniques resulted in a marked decrease in
short-term and long-term morbidity and mortality when treating patients with
mitral regurgitation. Some believed that this resulted from maintenance of the
mitral annular papillary muscle continuity during mitral valve repair. Subsequent
experimental and clinical studies have validated the positive short-term and long
term effects of maintaining the integrity of the mitral valve subvalvular
apparatus. This article considers the history of the clinical use of preservation
of the subvalvular apparatus, the physiologic studies examining this concept, and
the clinical data available on its use. It also examines the following: 1) mitral
stenosis versus mitral regurgitation and the preservation of the subvalvular
apparatus; 2) whether the anterior, posterior, or both areas of the subvalvular
apparatus should be preserved; and 3) the surgical techniques for the
preservation of the subvalvular apparatus and valve implantation.
PMID- 10191970
TI - An overview of combined heart and kidney transplantation.
AB - This review describes to date the experience with combined heart-kidney
transplant (HNTx) from a single donor. HNTxs are very uncommon relative to single
organ transplants of the heart and kidney, as well as combined kidney-pancreas
and combined kidney-liver transplants. Two groups of patients seem to be
candidates for HNTx: 1) those with end-stage heart disease and fixed
(nonreversible) renal disease, and 2) those with end-stage renal disease and
severe cardiac disease unamenable to other treatment. In both groups, significant
disease should be limited to the heart and kidney. Reports to date generally
suggest decreased cardiac rejection in HNTx relative to heart-only transplants.
Renal rejection in HNTx seems markedly reduced relative to kidney-only
transplants. Simultaneous rejection of both organs is very uncommon, and,
therefore, surveillance of both organs is necessary. Short-term patient survival
seems to be acceptable in HNTx. Long-term patient and graft survival remains
unknown, and further multi-center reports are needed.
PMID- 10191971
TI - Simultaneous donor bone marrow and cardiac transplantation: can tolerance be
induced with the development of chimerism?
AB - Mixed bone marrow chimerism (mixed chimerism) is defined by the coexistence of
two genetically different bone marrow stem cells in an individual. The chimeric
immune system recognizes donor antigen as self, yet is capable of mounting a
normal response to third-party antigens. In animal models, mixed chimerism
confers donor-specific tolerance for solid-organ and cellular grafts: tissue from
the bone marrow donor is permanently accepted by mixed chimeras in the absence of
conventional immunosuppressive agents. Clinical application of mixed chimerism to
induce transplantation tolerance requires novel approaches to safely and reliably
achieve engraftment of donor bone marrow in transplant recipients. Recent
advances offer potential solutions to these obstacles and suggest that the
application of mixed chimerism to induce tolerance to transplanted organs may
soon be a clinical reality.
PMID- 10191972
TI - Relationship of fibrin deposition in microvasculature to outcomes in cardiac
transplantation.
AB - The development of transplant coronary artery disease (CAD) is directly
associated with outcome in cardiac transplantation. The relationship between
microvascular fibrin deposition early after transplantation and subsequent
development of transplant CAD is discussed in this article. In this article the
presence of microvascular fibrin and its association with other prothrombogenic
changes within the cardiac microvasculature, such as loss of vascular
antithrombin, depletion of arteriolar tissue plasminogen activator, and presence
of arterial and arteriolar endothelium activation, as well as changes in
circulation associated with prothrombogenic changes that have predictive value
for subsequent transplant outcome are presented and discussed. Novel therapeutic
approaches that may prevent the development of transplant CAD and consequently
affect outcome are considered.
PMID- 10191973
TI - Impact of intravascular ultrasound in understanding transplant coronary artery
disease.
AB - Intravascular ultrasound imaging has been recognized as a sensitive tool to study
early transplant vasculopathy lesions. An early examination performed soon after
transplantation allows one to study donor atherosclerosis. Further, serial follow
up imaging with meticulous site matching provides important information regarding
the progression of donor atherosclerosis and the development of transplant
vasculopathy lesions. This review highlights the contribution of intravascular
imaging in understanding the transplant coronary artery disease. This review also
outlines various methodologies employed by different investigators, and stresses
the strengths and weaknesses of these methodologies for correct interpretation as
well as comparison of data from different studies.
PMID- 10191974
TI - Noninvasive detection of cardiac transplant rejection using electronic
monitoring.
AB - Cardiac transplantation has become the therapy of choice for the treatment of end
stage congestive heart failure. One of the major problems after cardiac
transplantation is acute cellular rejection. The diagnosis of rejection is
crucial to the management of transplant patients because rejection must be
successfully diagnosed and reversed. Endomyocardial biopsy is the major method
for detecting cardiac transplant rejection; however, this approach is invasive
and is associated with morbidity and mortality. One noninvasive approach for
detecting rejection is to monitor changes in the intramyocardial electrograms
using pacemakers. Changes in the ventricular evoked response amplitude (VERA)
obtained during ventricular pacing have been correlated with the presence of
acute cellular rejection in both single center studies in Europe and a
multicenter trial in five transplant centers in the United States. Given the high
negative predictive value for the VERA, this approach may provide a screen to
determine if individual patients require more invasive procedures such as
endomyocardial biopsy and may aid in reducing the number of biopsies needed.
PMID- 10191975
TI - Current therapies for secondary prevention after myocardial infarction.
AB - Compelling evidence from clinical trials confirms the benefits of secondary
prevention for patients with known coronary disease. Preventive therapies
initiated after myocardial infarction can extend overall survival, reduce
subsequent myocardial infarction, decrease the need for revascularization, and
improve quality of life. All patients with atherosclerotic cardiovascular disease
should be considered for lipid lowering therapy, antiplatelet agents, beta
blockers, and control of hypertension. Long-term therapy with angiotensin
converting enzyme inhibitors should be continued in patients with systolic
dysfunction. Hormone replacement therapy has not been shown to benefit
postmenopausal women when initiated after myocardial infarction. Smoking
cessation, weight control, exercise, and appropriate diet represent important
behavioral modifications.
PMID- 10191976
TI - A review of the sixth report of the Joint National Committee on Prevention,
Detection, Evaluation, and Treatment of High Blood Pressure.
AB - Hypertension is a major modifiable risk factor for cardiovascular diseases. After
decades of improvement, population surveys demonstrate disturbing downward trends
in the rates of awareness, treatment, and control of this disorder in recent
years. Over this same time period, there has been a slight increase in the
incidence of strokes, and a steady rise in the incidence of end-stage renal
disease and the prevalence of congestive heart failure, conditions in which
hypertension plays a prominent role. Results of recent studies support the
possibility that lifestyle modifications may be effective for prevention of
hypertension. Treatment of established hypertension involves lifestyle
modifications and drug therapies designed to control blood pressure and reduce
overall cardiovascular risk. Both threshold blood pressure levels for initiating
drug therapy and goal blood pressure levels with treatment are individually
determined based on the presence or absence of additional cardiovascular risk
factors and hypertension target organ injury or clinical cardiovascular disease.
Recent clinical trials support the value of lower goal blood pressures for
patients with diabetes, heart failure, and renal disease. The presence or absence
of comorbid conditions often determines specific drug choices. Diuretics and beta
blockers remain the drugs of choice in uncomplicated hypertension. Additional
studies confirm the benefits of treating isolated systolic hypertension in the
elderly. The Sixth Report of the Joint National Committee on Prevention,
Detection, Evaluation, and Treatment of High Blood Pressure provides a practical,
evidence-based resource to help health care providers meet the public health
challenges of preventing and controlling hypertension.
PMID- 10191977
TI - The prevention of cardiovascular disease in blacks.
AB - Cardiovascular disease (CVD) in black patients involves a complex interplay of
risk, geographic, socioeconomic, and cultural factors. Modifiable risk factors
such as high blood pressure, diabetes, cigarette smoking, high blood cholesterol,
and physical inactivity contribute to the excess CVD mortality and morbidity in
blacks. Health perceptions, health care seeking behavior, and willingness to
submit to long-term preventive therapies are significantly influenced by cultural
and socioeconomic factors. Early detection and control of these risk factors are
particularly important because blacks tend to have multiple cardiovascular risks.
The importance of churches and religious organizations in the black community
should be harnessed by long-term strategies of CVD prevention. Emphasis on
training of minority health care professionals who are most likely to practice in
medically underserved areas should involve minority health professional schools.
In the final analysis, CVD prevention in blacks should focus on control of risk
factors; however, the role of environmental factors should be recognized,
including socioeconomic status on access to health care and prevention. Long-term
strategies of CVD prevention must involve active collaboration of health care
providers and researchers to develop and test effective strategies. Churches and
other religious organizations are effective but underutilized partners in CVD
prevention in blacks.
PMID- 10191978
TI - Metabolic risk factors for coronary heart disease: current and future prospects.
AB - In this review, data are reviewed concerning various metabolic risk factors that
have been associated with coronary heart disease, drawing upon the experience of
observational studies and clinical trials. Topics include lipids, glycemia,
secular trends, hematologic factors, homocysteine, estrogen replacement, and
familial and genetic factors. Using combinations of these types of factors in
multivariate risk profiles is discussed, along with the opportunity to
incorporate some of these factors into the prediction of coronary heart disease
in the future.
PMID- 10191979
TI - Lipoprotein(a), homocysteine, and remnantlike particles: emerging risk factors.
AB - Although lipoprotein(a) [Lp(a)] was first described more than 35 years ago,
adequate prospective data have only recently supported Lp(a) as an independent
risk factor for coronary heart disease (CHD). In vitro studies suggest that Lp(a)
contributes to atherogenesis directly by cholesterol uptake and indirectly by the
inhibition of fibrinolysis. In patients with CHD or a significant risk for CHD,
Lp(a) should be measured and treated with either niacin or estrogen if the
patient has Lp(a) cholesterol levels of more than 10 mg/dL or an Lp(a) mass of
more than 30 mg/dL. In addition, homocysteine and remnantlike lipoprotein
cholesterol are strongly supported by prospective or population-based prevalence
data as independent risk factors for CHD. Homocysteine levels of more than 14
mumol/L should be treated with vitamin supplements of folate, B6, and B12.
Remnantlike lipoprotein cholesterol is the product of a novel immunoassay that
separates the partially hydrolyzed triglyceride-rich remnant particles. The
association of these particles with CHD risk in women may explain the small
independent CHD risk that triglycerides have in women in the Framingham Heart
Study. A clear therapeutic intervention has not been documented but may include
diet, fibric acid derivatives, or hydroxymethylglutamyl coenzyme A reductase
inhibitors.
PMID- 10191980
TI - Bibliography Current World Literature. Valvular heart disease.
PMID- 10191982
TI - Bibliography Current World Literature. Prevention.
PMID- 10191981
TI - Bibliography Current World Literature. Heart transplantation.
PMID- 10191983
TI - Rolling circle amplification of DNA immobilized on solid surfaces and its
application to multiplex mutation detection.
AB - A new method of amplifying short DNA molecules immobilized on a solid support has
been developed. This method uses a solid-phase rolling circle replication
reaction, termed rolling circle amplification (RCA). The probe consists of a
single-stranded DNA primer anchored at the 5' terminus to a solid support and a
single stranded DNA template hybridized to the immobilized primer. Here, DNA
ligase was used to circularize the template, and DNA polymerase I was used to
extend the immobilized primer in a rolling circle replication reaction. This
method was used to identify a known polymorphism in BRCA1 exon 5. These results
demonstrate that RCA offers considerable promise to facilitate effective mutation
screening of DNA using a solid-phase format.
PMID- 10191984
TI - Detection of foetal cells in maternal blood and prenatal sex determination by in
situ hybridization. Procedure verification.
AB - We describe an enrichment of foetal cells from maternal blood with a combination
of double density gradient and Magnetic Activated Cell Sorting (MACS) of CD71,
glycophorin A (GPA), CD34 and CD36 antibodies labeled cells followed by
fluorescence in situ hybridization (FISH) with chromosome-specific DNA probes for
determination of foetal sex.
PMID- 10191985
TI - Selection analysis of single-stranded clones using solid-phase techniques.
AB - An efficient selection analysis of single-stranded DNA fragments using
subtractive hybridization on magnetic beads and fluorescence-based fragment
analysis is described. This approach facilitates either direct cloning of
captured fragments or removal of common clones from cDNA or shot-gun clone
libraries.
PMID- 10191986
TI - PCR based targeted genomic and cDNA differential display.
AB - We previously described a targeted genomic differential display method (TGDD:
Broude NE, Chandra A, Smith CL. Differential display of genomic subsets
containing specific interspersed repeats. Proc. Natl. Acad. Sci. USA 1997;94:4548
53). In that method, presently characterized as method I, targeting was
accomplished by capturing DNA fragments containing specific a sequence by
hybridization with complementary single-stranded DNA. The captured fragments were
amplified by PCR. Here, we describe method II where targeting is accomplished by
PCR using primers specific to the target sequence. Method II takes advantage of
PCR suppression to eliminate fragments not containing the target sequence
(Siebert PDA, Chenchik A, Kellogg DE, Lukyanov KA and Lukyanov SA. An improved
PCR method for walking in uncloned genomic DNA. Nucleic Acids Res 1995;23:1087
1088). Targeting focuses analysis on and around interesting areas and
additionally serves to reduce the complexity of the amplified subset. These
approaches are useful to amplify genome subsets containing a variety of targets
including various conserved sequences coding for cis-acting elements or protein
motifs.
PMID- 10191987
TI - Nucleus extraction from single mounted tissue sections.
AB - Extraction of nuclei from unmounted archived tissue has become a method widely
used for molecular cytogenetic investigations. It is a suitable approach to take
advantage of the large series of formalin fixed and subsequently paraffin
embedded material which has been collected in the times before interphase
cytogenetic analysis has become possible. We present a new kind of assay for the
extraction of nuclei from one single mounted tissue section; the extracted
interphase nuclei are suitable very well for a fluorescence in situ hybridization
(FISH) approach. The method described has been successfully used for the analysis
of the INT2/FGF3-amplicon in 20 samples of oral squamous cell carcinoma.
PMID- 10191988
TI - Mortality and causes of death in eating disorders in Denmark 1970-1993: a case
register study.
AB - OBJECTIVE: The aim of this study is to describe mortality rates and causes of
death for patients with eating disorders. METHOD: By means of record-linkage, the
study includes all patients admitted and diagnosed as suffering from an eating
disorder according to the ICD-8 classification system during the period 1970-1993
at any Danish psychiatric (since 1970) or somatic department (since 1977). The
study includes 2,763 cases, of which 237 are males. Maximum follow-up time is 23
years and mean follow-up time is 10.3 years. RESULTS: Crude mortality at follow
up is 8.4%. A significant excess mortality is demonstrated since the standardized
mortality ratio (SMR) of the total patient population is 6.69 (CI 5.68-7.83) and
the highest rate ratio (RR) of 14.92 (CI 9.66-22.03) relates to women aged 25-29.
DISCUSSION: The study documents a significant excess mortality among eating
disordered patients.
PMID- 10191989
TI - A prospective study of the influence of eating-disordered mothers on their
children.
AB - OBJECTIVE: This study examined the effects of eating disordered mothers on their
children. METHOD: Women with a past or present eating disorder (ED; N = 41) and
non-eating disordered women (NED); N = 153) and their offspring were followed
prospectively. RESULTS: Female infants of ED mothers sucked significantly faster
and were weaned 9 months later than offspring of NED mothers. ED mothers fed
their children on a less regular schedule, used food for nonnutritive purposes,
and demonstrated significantly higher concern about their daughters' weight than
NED mothers from 2 years of age onward. At 5 years, the offspring of ED mothers
were reported to demonstrate greater negative affect than the offspring of NED
mothers. DISCUSSION: The female offspring of ED mothers demonstrate a high
avidity for feeding early in life which, combined with increased maternal concern
over their daughters weight and the use of food for nonnutritive purposes, may
pose a serious risk for the later development of an eating disorder.
PMID- 10191990
TI - Parental input and weight concerns among elementary school children.
AB - OBJECTIVE: This study examined the relative contributions of mother's and
father's direct comments about child's weight and modeling of weight concerns
through their own behavior on child's body esteem, weight-related concerns, and
weight loss attempts. METHOD: Parents, 131 mothers and 89 fathers, of fourth and
fifth grade boys and girls completed a brief survey which included measures of
their own dieting attempts, concerns about their own shape, complaints about
their own shape, and beliefs about calorie-restrictive dieting as well as the
frequency of their comments to their child about the child's weight. Children
were surveyed using the Body Esteem Scale as well as questions about their weight
related concerns and weight loss attempts. RESULTS: Direct parental comments,
especially by the mother, seemed to be more powerful influences than parental
modeling of weight and shape concerns, although parental modeling did affect the
child's beliefs and behaviors. Girls appeared to be more affected than did boys.
DISCUSSION: Parental comments and modeling do appear to affect elementary school
children's weight and shape-related attitudes and behaviors. Such parental
behavior may be an appropriate target in prevention programs.
PMID- 10191991
TI - The role of familial values in understanding the impact of social class on weight
concern.
AB - OBJECTIVE: To examine the role of social class on aspects of weight concern and
to assess the possible impact of values on mediating this association. METHOD:
Two hundred fifty-seven girls ranging in age from 13 to 16, from either a fee
paying inner city independent girls school (higher class school, n = 135) or a
state comprehensive, inner city girls school (lower class school, n = 122)
completed a questionnaire concerning their profile characteristics (age, social
class), aspects of their weight concern, and their own and their perceptions of
their significant others' values (achievement, family life, and physical
appearance). RESULTS: The results showed consistent effects of class on weight
concern, with the higher class subjects reporting higher levels of restrained
eating, greater body dissatisfaction, and body distortion than their lower class
counterparts. The results also showed an effect of class on values, with the
lower class subjects placing more importance on family life from both their own
perspective and that of their parents and friends, and rating their friends as
valuing achievement and physical appearance more than the higher class subjects.
In terms of the best predictors of weight concern, the results showed that higher
levels of restrained eating were related to being from a higher class, placing
greater importance upon physical appearance, preferring a thinner ideal female
body, and placing less importance upon family life; greater body dissatisfaction
was related to being from a higher social class, placing greater importance upon
physical appearance and a lower importance upon achievement, and greater body
distortion was related to being from a higher social class and a high value
placed upon physical appearance. CONCLUSION: The results indicate both a direct
social class/weight concern link and a relationship which is mediated by values.
The results are discussed in terms of developing an improved measure of class
values and the relatively stable nature of class boundaries.
PMID- 10191992
TI - Problem eating attitudes and behaviors in young children.
AB - OBJECTIVE: The factor structure of the Children's Eating Attitudes Test (ChEAT)
and the predictors of problem eating were examined in young boys and girls.
METHODS: Two hundred and twenty eight children from Grades 2 and 4 completed
questionnaires which examined problem eating attitudes and behaviors, body image,
and self-concepts. RESULTS: Four factors were found for girls and boys. The
girls' four factors, Dieting, Food Preoccupation, Social Pressure to Eat, and
Restricting and Purging, corresponded closely to previous studies with older
girls and women. Four different factors were found for the boys, Global Problems,
Dieting versus Purging, Dieting and Food Preoccupation, and Emotional Eating.
However, dieting behaviors in both girls and boys were predicted by poorer body
image and in boys emotional concerns about eating were predicted by poorer body
image and lower self-concepts. DISCUSSION: There is still relatively little
research that has examined problem eating attitudes and behaviors of boys and
men. As boys tend to report infrequent dieting, we may need to focus more on the
emotional concerns about eating and becoming overweight as a potential indicator
of eating problems in boys.
PMID- 10191993
TI - Binge eating disorder in females: a population-based investigation.
AB - OBJECTIVE: The authors investigated the prevalence of binge eating behavior in a
general female Austrian population. METHOD: A random sample of 1,000 women (age
range 15a to 85a) was interviewed by dieticians over the phone. Some screening
instruments were used to detect binge eating behavior. RESULTS: Of the entire
sample, 122 met the diagnostic criteria for binge eating, 84 for binge eating
syndrome, and 33 for binge eating disorder (BED). The point prevalence of bulimia
nervosa was 1.5%. Women with binge eating episodes carried out more frequently
one or more diets within the previous year, and more frequently exhibited a
restrained eating behavior than did women without binge eating behavior.
Underweight women more often met the diagnostic criteria for bulimia nervosa
nonpurging type than did normal weight, overweight, and obese women, while
overweight and obese women more frequently met the diagnostic criteria for BED.
DISCUSSION: Our findings indicate that binge eating appears to be a fairly common
behavior in women. Dieting, chronic restrained eating, and excessive exercise may
be important triggers for BED and bulimia nervosa.
PMID- 10191994
TI - Eating pathology before and after bariatric surgery: a prospective study.
AB - OBJECTIVE: The objectives of the study were (1) to determine the prevalence of
eating pathology in patients before bariatric surgery and at follow-up; (2) to
assess the relationship of presurgical eating pathology to various measures of
psychopathology; and (3) to assess the relationship between presurgical eating
pathology and outcome. METHOD: One hundred sixteen patients were evaluated prior
to surgery and at follow-up an average of 5.5 years after surgery. RESULTS:
Preoperative binge eating occurred in 52% of patients, 16% met criteria for binge
eating disorder, and 10% had the night eating syndrome. All three forms of
presurgical eating pathology were statistically associated with cognitive
distortions. At follow-up, 33% of patients were vomiting at least weekly. There
was no relationship between presurgical eating pathology and weight outcome or
presence of vomiting at follow-up. DISCUSSION: Although postoperative vomiting
usually does not represent purge behavior, it may represent failed attempts to
binge.
PMID- 10191995
TI - Personality and the prediction of weight loss and relapse in the treatment of
obesity.
AB - OBJECTIVE: This prospective study examined whether stable personality traits, as
measured by the Karolinska Scales of Personality (KSP), predicted initial weight
loss or long-term maintenance in obesity patients. METHOD: The KSP was
administered to 102 obese patients prior to entering an 8-week weight loss
program. Patients were weighed again at the end of treatment and at 3- and 12
month follow-up. RESULTS: The KSP did not predict initial weight loss after the 8
week program. Several of the KSP scales (Muscle Tension, Monotony Avoidance,
Suspicion, and Guilt) had weak associations with 12-month relapse status. Weight
gain at the 3-month follow-up was the strongest predictor of 12-month relapse
status (O.R. = 0.46; 95% C.I. = 0.32, 0.66). DISCUSSION: Personality traits, as
measured by the KSP, do not appear to be important predictors of initial weight
loss or 12-month relapse status. Personality assessment may not substantially
contribute to predicting treatment outcome in obesity research.
PMID- 10191996
TI - Laxative withdrawal in eating disorders: treatment protocol and 3 to 20-month
follow-up.
AB - OBJECTIVE: This article describes a treatment protocol for laxative withdrawal
and presents some preliminary information about response to treatment at 3 to 20
month follow-up. METHOD: Patients were contacted 3 to 20 months after admission
and evaluated with a shortened form of the Eating Disorders Examination (EDE).
RESULTS: Fifty-seven percent of patients were abstinent from laxatives at follow
up and there were significant reductions in laxative-related symptom variables.
Abstinence from laxatives was not accompanied by any other changes in eating
behavior and was not associated with any pretreatment variables that were
assessed. DISCUSSION: It appears to be feasible to withdraw patients from
laxatives as an isolated intervention with a reasonably high rate of success.
PMID- 10191997
TI - The impact of emotion upon eating behavior: the role of subliminal visual
processing of threat cues.
AB - OBJECTIVE: Previous research has demonstrated that subliminal threat cues can
influence eating behavior. The present study examined whether this effect is due
to general emotional activation (by comparing positive and negative emotional
cues), whether it is a product of specific negative emotional activation, and
whether it can be achieved by activating appetite-related schemata. METHOD: One
hundred women avoided food for at least 4 hr and then completed a task where they
were exposed to one of five subliminal visual cues. The dependent variable was
the amount eaten subsequently. RESULTS: Women who were exposed to the abandonment
cue (lonely) ate significantly more than those who were exposed to the neutral
cue (gallery), the positive emotional cue (happy), or the appetitive cue
(hungry). Those with unhealthy eating attitudes also ate more after the hostile
emotion cue (angry) than after the neutral cue. CONCLUSIONS: The results support
cognitive models that stress an important role for threat processing in the
facilitation of eating, rather than models advocating the centrality of food
related information. Abandonment schemata appear to be activated at an earlier
stage than appetite-related schemata.
PMID- 10191998
TI - An experimental test of the relationship between self-esteem and concern about
body shape and weight in restrained eaters.
AB - OBJECTIVE: Although self-esteem and overconcern with body shape and weight are
considered to be closely connected in bulimia nervosa, little empirical research
has been done to investigate the alleged link. METHOD: In this study, we examined
experimentally whether overconcern with body shape and weight was connected with
self-esteem in an analogue sample of high restrained eaters by means of a
subliminal lexical decision task. RESULTS: It could indeed be demonstrated that
low self-esteem and overconcern with body shape and weight are associated in high
restrained eaters: after priming low self-esteem, the accessibility of
subliminally presented body shape and weight stimuli was increased. The effect
was not found with a supraliminal lexical decision task. DISCUSSION: Apparently,
the automatic, nonconscious processing of body shape and weight words was
influenced in high restrained eaters with a low state self-esteem, whereas the
strategic, conscious processing was not. As soon as the body shape and weight
stimuli were processed consciously, the initial increased accessibility was
countered and the effect disappeared.
PMID- 10191999
TI - Night eating and binge eating disorder in obese patients.
AB - OBJECTIVE: To investigate the relationships between binge eating disorder and
night eating in severely obese patients. DESIGN: Longitudinal study following
biliopancreatic diversion, when any preoccupation with food and weight is
completely abandoned. MATERIALS AND METHODS: Structured interview prior to the
operation and at the 1, 2, and 3-year follow-up visit. RESULTS: Nearly complete
disappearance of binging behavior and no changes in the frequency of night
eating. CONCLUSION: Binge eating and night eating are widely overlapping but
different behaviors; night eating appears to be fully independent of
preoccupation with food and dieting.
PMID- 10192000
TI - Body image, psychological functioning, and parental feedback regarding physical
appearance.
AB - OBJECTIVE: To investigate the role of parental appearance-related commentary,
body image, and psychological functioning in females and males. METHOD:
Retrospective reports of teasing and appearance-based feedback were assessed,
along with current levels of body image and overall psychological functioning.
RESULTS: Women and men did not differ in their reports of comments received from
mothers, however, women received significantly more appearance-related messages
from fathers. Correlational analyses demonstrated significant relationships
between feedback and body satisfaction for women, but not for men. Regression
analyses indicated that fathers' and mothers' teasing about weight were
predictive of daughters' body image. For both males and females, psychological
functioning was significantly predicted from the combination of mothers' and
fathers' feedback regarding appearance. DISCUSSION: The findings further support
an emerging theoretical model of appearance-related commentary as a factor in
body image disturbance and overall psychological functioning.
PMID- 10192001
TI - Psychological factors in nutritional disorders of the elderly: part of the
spectrum of eating disorders.
AB - OBJECTIVE: To illustrate common psychogenic factors involved in undereating and
undernutrition in the elderly. METHOD: Two cases are described. RESULTS: In the
context of age-related physical and social factors, obsessional, phobic, and
hypochondriacal anxieties can lead to significant food restrictions and
undernutrition. DISCUSSION: Psychogenic factors need to be considered in
undernutrition of the elderly and the phenomena considered in the spectrum of
eating disorders.
PMID- 10192002
TI - The reliability of the Eating Disorder Examination-Self-Report Questionnaire
Version (EDE-Q).
AB - OBJECTIVE: This research investigated the internal consistency and test-retest
reliability of the Eating Disorder Examination-Self-Report Questionnaire Version
(EDE-Q), a 41-item measure adapted from the Eating Disorder Examination (EDE).
The EDE is a structured clinical interview assessing the key behavioral features
and associated psychopathology of eating disorders. RESULTS: Results indicated
excellent internal consistency and 2-week test-retest reliability for the four
subscales of the EDE-Q: Restraint, Weight Concern, Shape Concern, and Eating
Concern. There was somewhat less stability in the items measuring the occurrence
and frequency of the key behavioral features of eating disorders. CONCLUSIONS:
Overall, results support the psychometric adequacy of the EDE-Q.
PMID- 10192003
TI - Patulous eustachian tube in a case of adolescent anorexia nervosa.
AB - Autophonia, the hyperperception of one's own voice and breathing, is one of the
consequences of rapid weight loss and is explained within the syndrome of the
patulous eustachian tube. We report on a female adolescent, who presented to an
otologist for autophonia and was finally diagnosed with anorexia nervosa. The
occurrence and relevance of this symptom in eating-disorder patients is
discussed.
PMID- 10192004
TI - Topography of averaged electrical brain activity relating to interhemispheric
dynamics in normal humans: where does the critical relay take place?
AB - Interhemispheric relay time (IHRT) was investigated using a 16-electrode montage
in 10 normal subjects during a simple visual reaction time task (Poffenberger
paradigm). The P1 latency was the dependent measure. Response-locked components
were separated from the stimulus-locked components based on the reaction times
using a Woldorff-like filter. The issues of theoretical interest were the
following: (1) does the responding hand modulate IHRT estimates as a function of
electrode site, or stimulated field?; (2) what are the respective advantages of
various pairs of symmetrical across-midline electrode sites for tracking IHRT?;
and (3) what are the respective advantages of symmetrical vs. asymmetrical across
midline electrode site-pair configurations for tracking IHRT? There were
significant lags attributable to IHRT in both evoked potential P1 latencies and
in reaction times--but these were uncorrelated. The responding hand was not found
to significantly modulate IHRT estimates derived from the P1 peak latency of
response-corrected ERPs. Anterior sites yielded more precocious components and
briefer estimates of IHRT which were closer to those observed in reaction time
estimates. However, posterior leads yielded more reliable estimates. Various
analyses suggested that IHRT can be tracked, very vaguely, with asymmetric
configurations as well as symmetric ones, each for different reasons.
PMID- 10192005
TI - An investigation of the event-related slow-wave potential (0.01-2 HZ) in normal
children.
AB - Previous research has indicated that the auditory ERPs of children are dominated
by a frontal negative slow-wave. This paper outlines a preliminary attempt to
separate event-related low-frequency activity from traditional ERP components as
found in older subjects. An active auditory oddball task was completed by 30
normal children aged from 8 to 18 years, and ERPs to target and standard stimuli
were derived. The original ERP files were digitally filtered to calculate
separate ERPs containing only 0.01-2 Hz activity (termed the SW-ERP) or 2-12 Hz
activity (termed the RESIDUAL ERP) for each subject. The SW-ERP was maximally
correlated with the slow-wave factor from a principal components analysis of the
original target and standard waveforms. The SW-ERPs to target stimuli contained
an early negative component which showed an age-related decrease, and a late
positive component which did not. The SW-ERP was found to be partly responsible
for the differences in component amplitude and morphology between sites observed
in the raw ERPs.
PMID- 10192006
TI - Alpha-band oscillations in visual cortex: part of the neural correlate of visual
awareness?
AB - It was originally proposed that synchronized gamma-band oscillations in neurons
of the visual cortex constitute the neural correlate of visual awareness. Two
hypotheses are presented in this article: (a) both alpha-band and gamma-band
oscillatory activity correspond to visual awareness; and (b) alpha-band activity
occurs in the parvocellular processing pathway and gamma-band activity occurs in
the magnocellular pathway, and the two modes of oscillation are correlated. It is
further proposed that the frequency of the gamma-band oscillation in a group of
neurons representing a particular visual scene segment is three times that of the
alpha-band oscillation in the neurons representing the same segment. These
hypotheses are discussed in relation to recent neurophysiological and
psychophysiological experiments.
PMID- 10192007
TI - Modulation of the acoustic startle reflex by emotionally-toned film-clips.
AB - It has been widely reported that the eyeblink component of the acoustic startle
reflex can be modulated by emotionally-toned slide stimuli; pleasant slides
reduce eyeblink amplitudes whereas unpleasant slides enhance them. The present
study examines the modulation of the acoustic startle reflex by short (2-min)
film-clips classified as pleasant, unpleasant or neutral, on the basis of
subjective ratings. These film-clips were also evaluated with respect to their
test-retest reliability in producing affective states as well as modulating
startle reflexes. Overall, results showed significant reduction of startle during
pleasant clips and augmentation during unpleasant clips. However, on first
showing, one of the two unpleasant clips (a medical demonstration film depicting
details of toe surgery) actually inhibited the startle reflex rather than
augmented it. This is discussed in terms of the proposition that only stimuli
which arouse fear can be guaranteed to augment startle; stimuli that are
repulsive may produce perceptual and emotional 'blunting' that reduces startle
amplitude.
PMID- 10192008
TI - Effects of 20-min audio-visual stimulation (AVS) at dominant alpha frequency and
twice dominant alpha frequency on the cortical EEG.
AB - The effects of audio-visual stimulation at the dominant alpha frequency and twice
dominant alpha frequency on the EEG were investigated. An eyes-closed baseline
EEG determined each subject's dominant alpha frequency. Subjects were stimulated
at their dominant alpha frequency and at twice dominant alpha frequency for 20
min on two occasions. A 30-min post-session eyes-closed EEG was recorded after
each session. Power data were analyzed for 19 locations in six bandpasses using
repeated-measures ANOVAs and appropriate post-hoc tests. Alpha stimulation
significantly increased power over baseline levels in the delta 1, delta 2,
theta, beta 1 and beta 2, with significant effects remaining 30 min later in beta
1. Twice alpha stimulation significantly increased theta, beta 1 and beta 2 power
over baseline levels, with significant effects remaining 30 min later in theta,
alpha, beta 1 and beta 2.
PMID- 10192009
TI - Startle potentiation by threat of aversive stimuli and darkness in adolescents: a
multi-site study.
AB - In recent years, the startle reflex has become an exciting new tool to
investigate affective responses to aversive stimuli in humans. The popularity of
this methodology is largely based on the substantial amount of animal research
available on this topic. Several procedures have been developed to examine
startle potentiation in humans, but most studies have been carried out in adults
and may not be appropriate for children or adolescents. The present study is a
multi-site project (Yale University, Harvard University, and the University of
Minnesota) investigating two new procedures to examine the potentiation of
startle in adolescents. The subjects were 50 male and female aged 13-17 years
old. One procedure examined fear-potentiated startle to the threat of an
unpleasant airblast directed to the larynx. The second examined the facilitation
of startle in darkness. Potentiation was found using each procedure and the
degree of potentiation was similar across laboratories. These results suggest
that both the threat of an airblast and darkness can reliably be used to examine
startle potentiation in young subjects.
PMID- 10192011
TI - Australia and its orthopaedic association.
PMID- 10192010
TI - Self presentation and cardiovascular reactivity.
AB - This research was concerned with two issues: first, whether cardiovascular
response patterns to a social stressor (i.e. self-presentation under evaluative
circumstances) differ as a function of one's ability to control the impression
one makes on others; second, whether cognitive appraisals are necessary or
sufficient for the cardiovascular components of emotional arousal. Forty-two male
subjects (Ss), monitored for cardiac impedance and blood pressure, were shown a
previously recorded videotape of themselves in which each S verbally described
personal aspects about himself. Ss in an Active condition were allowed to mark
segments of the tape they wanted to re-shoot before the tape was evaluated by
reviewers. Ss in a Passive condition viewed their tape but could not indicate
whether to revise it. Control conditions allowed assessment of the activity
entailed in tape marking and of evaluation per se. Self-reports of stress,
threat, and coping ability regarding the upcoming task were taken. Blood pressure
elevations occurred equally in both experimental conditions, but apparently
through different underlying mechanisms. The Active condition produced myocardial
responses (increased ejection fraction), while the Passive condition produced a
vascular response (increased total peripheral resistance). However, while
cardiovascular reactivity patterns did differ as a function of the opportunity to
control the impression one could make on evaluative others, they did not differ
as a function of having appraised the task as a challenge or as a threat.
Consideration also is given to the conditions necessary for cognitive appraisal
to occur and to influence reactivity.
PMID- 10192012
TI - Australian orthopaedics overseas.
PMID- 10192013
TI - Survey of patient satisfaction after total arthroplasty of the hip.
AB - We have carried out a prospective study based on a series of interviews and
written questionnaires completed by 45 patients who underwent surgery, in an
effort to evaluate subjective patient satisfaction while recovering from total
hip arthroplasty. These patients all had operation for primary osteoarthrosis and
none had previously experienced orthopaedic procedures or psychiatric pathology.
Our study demonstrated that using standard quality-of-life questionnaires to
evaluate patient's subjective assessments is difficult, if not impossible. It
also established the need to combine questionnaires and open-ended interviews in
order to reveal subjective elements that should be taken into consideration by
the surgeon before deciding upon the need to operate. The analysis of the data
collected in this study highlights the fact that 50% of the patients express
feelings of frustration during a three month-long period following the operation,
in spite of their experiencing actual improvements of the operated hip. This
phase of temporary frustration winds down easily but it is only a year after
undergoing arthroplasty that some patients will enjoy all the subjective benefits
of the operation.
PMID- 10192014
TI - Intraoperative limb length measurement in total hip arthroplasty.
AB - In order to evaluate the efficacy of intraoperative measurement of limb length
inequality (LLI), we performed a prospective study on 64 patients who underwent
unilateral total hip arthroplasty. The patients were divided into 2 groups. In
Group I, the LLI was evaluated by the Shuck test, and in Group II by
intraoperative measurement using a Steinman pin and an adjustable caliper.
Preoperative LLIs assessed on radiographs averaged 1.18 cm in Group I and 0.37 cm
in Group II.
PMID- 10192015
TI - Infected total hip arthroplasty--the value of intraoperative histology.
AB - Intraoperative histology showed a sensitivity of 100% and a specificity of 98%.
These results were better than those observed for the other tests evaluated. Our
data provide evidence that intraoperative histology is useful tool in the
diagnosis of infected total hip arthroplasty.
PMID- 10192016
TI - Massive pelvic and femoral pseudotumoral osteolysis secondary to an uncemented
total hip arthroplasty.
AB - A 51 year-old man developed an extensive osteolytic response to wear debris in an
uncemented porous-coated total hip arthroplasty, with metal/polyethylene
interface, which had been implanted eighteen years previously. This reaction,
which involved the upper femur and the ilium, produced a mass which compressed
the pelvic viscera.
PMID- 10192017
TI - Limb salvage surgery in bone tumour with modular endoprosthesis.
AB - Thirty-three patients with bone tumours were treated by resection of the growth
and reconstruction with a Kotz modular endoprosthesis. The average follow-up was
for 50 months, ranging from 14 to 79 months. At the last review, 12 patients
(36%) had died due to the tumour and 9 others (27%) had metastases. All 4
patients with proximal tibial reconstruction had poor functional results, due to
an extension lag or to knee stiffness. Four of the six tumours of the proximal
femur were complicated by local recurrence or dislocation of the hip, and had
poor or fair functional results. Of the patients with distal femoral
reconstruction, 17 out of 22 had excellent or good functional results.
Reconstruction with a modular prosthesis after resection of a tumour gives
excellent or good functional results in more than three-fourths of the cases of
distal femur reconstruction, but it should be used with caution in the proximal
tibia and proximal femur.
PMID- 10192018
TI - Three-dimensional spiral CT scanning in children with acute torticollis.
AB - Three-dimensional spiral CT scanning is now becoming a common investigation in
children who have a history of acute torticollis. In the last year, 21
consecutive children who came to our unit with a history of acute torticollis
were assessed using standard plain radiographs and a 3-dimensional spiral CT
scan. Ten patients had a history of recent trauma. Spiral CT scanning revealed
that 13 children had atlanto-axial rotatory subluxation (AARS). Plain radiographs
had only a sensitivity of 33% and specificity of 71% in detecting AARS. Sixteen
children were treated using a Halter traction. Four failed to resolve clinically
and were put on a halo traction after 3-dimensional CT scanning again confirmed
residual AARS. Two children remained symptomatic after halo traction, with
persisting rotatory and anterior subluxation on repeat spiral CT. They both
underwent a posterior in-situ fusion, with no attempt at open reduction. Plain
radiography is limited in investigating acute torticollis in children. Spiral 3
dimensional CT reconstruction has an important role to play in both the
investigation and management of children who present with acute torticollis.
PMID- 10192019
TI - Soft tissue cover for the exposed knee prosthesis.
AB - This study assess the use of muscle flaps to cover exposed knee prostheses and
emphasises the need for early plastic surgery consultation. In five of the six
patients studied the wound was successfully covered and the knee prosthesis
salvaged with a reasonable functional outcome.
PMID- 10192020
TI - Bone-peg grafting for osteochondritis dissecans of the elbow.
AB - In the treatment of osteochondritis dissecans involving the elbow, we have used a
bone-peg graft taken from the proximal part of the ulna and inserted into the
defect. Thirty-two patients were followed from 2 to 10.5 years. The graft was
utilised in 20 elbows, and 6 of these also had concomitant removal of a loose
body. Another 6 elbows had removal of a loose body only. Ten elbows were treated
conservatively in 5 of these the outcome was unsatisfactory, including 4 in which
a bone-peg graft was later necessary. The bone-peg graft gave the best short-term
results. Bony union of the dissecans site and reconstitution of subchondral bone
required an average of 6.5 months. In 15 patients followed for a minimum of 5
years, the bone-peg graft was effective in limiting the development of
osteoarthritis. Bone-peg grafting is a reliable method for treating
osteochondritis dissecans of the elbow.
PMID- 10192021
TI - Ganglion cysts of the cruciate ligaments detected by MRI.
AB - Eight patients with ganglion cysts arising from the cruciate ligaments of the
knee joint underwent arthroscopic excision after the MR examination. The MR
findings, clinical features and arthroscopic findings were evaluated
comparatively.
PMID- 10192022
TI - Acute atraumatic compartment syndrome in the leg.
AB - The compartment syndrome is well recognised as occurring after trauma, but
atraumatic acute compartment syndrome is less widely known. We report 3 cases in
whom an acute compartment syndrome developed without major injury. Early
diagnosis and prompt treatment by decompressive fasciotomy is of vital importance
if limb function is to be preserved and complications avoided.
PMID- 10192023
TI - Intra-articular displaced fractures of the calcaneus. Operative vs non-operative
treatment.
AB - Twenty-eight patients with displaced intra-articular fractures of the calcaneus
treated by open reduction and fixation were compared with 30 patients with
similar fractures treated conservatively. Judged by the clinical and radiographic
criteria results were more satisfactory in the surgical group than in the
nonoperative group, although high rates of poor results were encountered in both
groups.
PMID- 10192024
TI - Osteochondroma of the first rib presenting as a prominent clavicle. A report of 2
cases.
AB - We describe and discuss two patients with osteochondromas of the first rib which
presented as prominence of the medial end of the clavicle.
PMID- 10192025
TI - Calcific myonecrosis.
AB - Calcific myonecrosis is a rare and late sequela of compartment syndrome, which
becomes symptomatic years after the initial trauma. We diagnosed this condition
in a 64-year old man, 42 years after he sustained a shot-gun wound to the right
lower leg. Total excision of a peripherally calcified, cystic mass, continuous
with the anterior tibial muscle belly resulted in complete resolution of
symptoms. Consideration of the diagnosis is warranted in patients with a history
of major injury who develop a soft tissue mass in the traumatized compartment.
The treatment of choice is marginal excision.
PMID- 10192026
TI - Spontaneous or traumatic premature closure of the tibial tubercle.
AB - A premature closure of the physis of the tibial tubercle in a young man has given
rise to a shortening of the tibia, a patella alta and a reversed tibial slope of
20 degrees with clinical genu recurvatum. After a proximal open wedge tibial
osteotomy all three postural deformities could be restored. The etiology of this
complex deformity is discussed.
PMID- 10192027
TI - Twelve years of cementless revision in retrospect. Wagner self-locking revision
stem and acetabular reinforcement cage.
PMID- 10192028
TI - [Fluvastatin in a comparative study. Are there substance-specific differences
between various CSE-inhibitors?].
PMID- 10192029
TI - [CREST or CREIST syndrome?].
PMID- 10192030
TI - [Vascular disease and cellular activation: exploration of cell adhesion phenotype
by quantitative flow cytometry].
AB - The pathogenesis of atheromatous and/or thrombotic vascular diseases involves
rheological parameters, soluble mediators and cellular agents. The many studies
that have tried to establish correlations between plasma factors, shear stress
and the risk of ischemia have left some questions unanswered. Current exploration
methods are now focusing on the determining role of cells. Activated cells
express adhesion molecules on their membranes, which allow to communicate in a
homo- or heterotypical manner. Quantifying adherence molecules on the surface of
platelets, leukocytes and endothelial cells provides an assessment of the
"adhesive phenotypical profile". Quantitative cytometry, using beads coated with
a known amount of immunoglobulins as calibrators, is perfectly suited, through
its multiple parameter analyses and the specificity provided by monoclonal
antibodies, for the quantification of membrane antigens. Measuring the adhesive
profile on the surface of cells that are implicated in vascular disease makes it
possible to correlate that phenotype to the ischemic risk in such diversified
pathologies or circumstances as intermittent angor, myocardial infarction,
angioplasty, insulin-dependent diabetes or pre-eclampsia. In addition, that
quantification permits monitoring the action of new therapeutical agents
targeting adherence molecules.
PMID- 10192031
TI - [Leg perforating veins].
AB - Our knowledge of the so-called incompetent leg perforating veins remains
questionable. Anatomic and hemodynamic studies show that perforators in a healthy
subject do not always convey inward flowing blood. Are incompetent perforating
veins more frequent with increasing severity of chronic venous disease? Answering
this question is difficult as no consensus has been established on how to assess
incompetent leg perforating veins and we have no gold standard to refer to. The
number of incompetent leg perforating veins is generally greater in severe
chronic venous disease although their frequency in clinical stage 4 to 6 (CEAP
classification) is not statistically different. This means that incompetent leg
perforating veins are not markers of severity of chronic venous insufficiency.
When analyzing published series which take into account etiology (primary or
secondary venous diseases) the frequency of incompetent perforating veins is
variable. Is surgical management required when incompetent leg perforating veins
are present? Angiologists and surgeons have not come to an agreement on this
point. What can be recommended today? It is generally accepted that the more
severe the disease the more worthwhile surgical treatment. Technically speaking,
subfascial endoscopic ligature is a promising new method although long-term
results are still lacking. We must watch carefully the prospective and randomized
studies which have been started in different countries. A lot of questions, only
a few reliable answers.
PMID- 10192032
TI - [Homolateral transposition of the internal jugular vein for axillo-subclavian
venous thrombosis (of effort)].
AB - Indications for treating subclavian vein obstruction are still being developed,
especially for endovascular procedures with or without first rib resection. This
article explores our experience with chronic and acute subclavian vein thrombosis
persisting after medical treatment. In our department of vascular surgery, we
have observed 2 cases of subclavian vein obstruction in 2 patients with Paget
Schroetler syndrome who developed major pain and edema in the dominant upper
limb. Initially, we managed these patients medically with thrombolysis and
anticoagulation. Then, as the significant symptoms persisted and venous
thrombolysis developed, we decided on surgical treatment. Because of hypertrophic
venous impairment, we used an aggressive procedure with venous bypass using
jugular vein transposition and temporary arteriovenous fistula. We observed
significant symptom relief and also perfect permeability of the venous bypass at
30 months. CONCLUSION: On the basis of our anecdotal experience and reports by
other groups, aggressive treatment with decompression (first rib resection and
scalenectomy) and jugular vein transposition could be recommended for persistent
subclavian vein thrombosis. Because of the presence of a thoraco-brachial outlet
syndrome the endovascular procedures should be completed by first rib resection.
PMID- 10192033
TI - [125 reinterventions for recurrent popliteal varicose veins after excision of the
short saphenous vein. Anatomical and physiological hypotheses of the mechanism of
recurrence].
AB - Recurrence of popliteal varicose veins has long been attributed to insufficient
excision of an incompetent short saphenous vein. Indeed, recurrence is still
frequent after surgery of the short saphenous. In order to assess the risk of
insufficient excision and study the mechanism of recurrence, we reviewed 125
popliteal procedures for recurrence after excision of an incompetent short
saphenous vein. Among this series, 48 were personal procedures and among these,
43 had been performed without preoperative ultrasound explorations prior to 1991.
Recurrences were classified into five categories (table I) according to the
anatomic presentation at reoperation. Type 1) 17 patients had an intact short
saphenous (13.6%) with either an inadequate incision or a simple recanalized
suture. Type 2) 53 patients had a long stump (42.4%) with new superficial
varicose communications. Type 3) 4 patients had a small residual and incompetent
short saphenous trunk (3.2%), 20 patients had both a long stump and an
incompetent residual trunk (16%). Type 4) 29 patients had incompetent popliteal
perforating veins (23.2%). Type 5) 2 patients developed recurrence on a new
varicose communication which followed the posterior nerves of the thigh. Among
our personal series, 43 reoperations for recurrence were performed without
preoperative duplex Doppler exploration. Among them, excision was insufficient in
38 (table II). The 5 patients reoperated after preoperative ultrasound
exploration had a popliteal perforating vein. Recurrence with a popliteal
perforator was significantly more frequent in men than in women (table III). The
delay to reoperation for popliteal recurrence after surgery of the short
saphenous (50% at 6 years) was significantly shorter than the delay to
reoperation for inguinal recurrence after surgery of the greater saphenous (50%
at 12 years) (table V). Insufficient excision was observed in 75.2% of the cases,
but 23.2% of the recurrences were due to the development of an incompetent
popliteal perforating veins. These perforating veins were residual stumps of the
short saphenous with complex pathways, unrecognized perforating veins associated
with the short saphenous at the first operation, or a new popliteal incompetence.
Ces perforantes de la fosse poplitee pourraient etre des moignons residuels de
petites saphenes a trajet complexe, des perforantes meconnues associees a la
petite saphene developing in several perforating vessels described in the
popliteal fossa. The lack of preoperative ultrasound data made it difficult to
interpret these recurrences. The development of perforating veins in the
popliteal fossa is a type of recurrence which is probably the expression of
particular hemodynamic phenomena in the popliteal venous circulation. These
phenomena probably involve the flexion of the popliteal vein, the contraction of
the calf muscles, and also popliteal valvular incompetence frequently
demonstrated in patients who develop short saphenous vein insufficiency.
PMID- 10192034
TI - [Popliteal venous aneurysms].
AB - Popliteal venous aneurysms are uncommon. We reviewed 101 cases reported in the
literature and our series of 11 operated cases to study the nosology and
therapeutic indications. In our series, there were 7 cases of unique dystrophic
aneurysms, 4 cases involving locoregional angiodysplasia: 3 cases with venous
hemodynamics and 1 case with arteriovenous flow. Pulmonary embolism developed in
2 cases. Ultrasonography provided the diagnosis. A sacciform aneurysm was found
in 10 cases and a fusiform aneurysm in 1 case. Venous repair was performed in all
cases: 9 endoaneurysmal sutures, 1 interposition of the medial gastrocnemius
vein, and 1 PTFE graft. Permeability was confirmed in all cases with no recurrent
embolism. These cases and the histological correlations describe the nosology of
dysplastic venous aneurysms which should be distinguished from dystrophic ectasia
of incompetent veins which is not associated with pulmonary embolism. Indeed,
pulmonary embolism is the most common complication revealing venous aneurysms
(table I). Doppler ultrasonography can provide early diagnosis before such
complications develop. Surgery is required for emergency cure in case of
pulmonary embolism and is warranted for preventive cure, generally by
endoaneurysmorraphic repair allowing venous permeability without the risk of
iterative embolism.
PMID- 10192035
TI - [Bilateral aneurysm of the common iliac artery and kidney pelvic ectopia:
endovascular treatment].
AB - We report the case of a 65-year-old man who developed chronic ischemia of the
lower limbs. The angiogram showed bilateral aneurysm of both common iliac
arteries in association with a left congenital pelvic kidney. The vascular supply
was made by with three arteries originating in the inferior mesenteric artery.
The aneurysms were treated with percutaneous stent grafts.
PMID- 10192036
TI - [Inflammatory arteriopathy of the arms in the course of Horton disease. Report of
six cases].
AB - We report 6 cases of upper limb involvement in giant cell arteritis; upper limb
involvement revealed the disease in 4 cases and clinical symptoms were present in
5 (upper limb pain, Raynaud's phenomenon). Upper limb pulses were not palpable
and blood pressure unmeasurable in all. Duplex ultrasonography found signs of
inflammatory arteriopathy in 4 cases (hypoechogenous halo of the arterial wall
and acceleration of flow velocity). Arteriography was performed in 5 cases and
showed long and regular stenoses. In the last case, arteriography was not done
because the duplex exploration gave an easier diagnosis. With this technique, the
diagnosis of upper limb involvement, frequent in autopsy series of giant cell
arteritis, might be made more often. Corticosteroid therapy is indicated and
surgery should be discussed only in emergency situations.
PMID- 10192037
TI - [Venous aneurysm of unusual localization revealed by a pulmonary embolism. Report
of two cases].
AB - We report two uncommon cases of venous aneurysm involving the soleus vein and the
saphenofemoral junction. Both cases presented with pulmonary embolism. Diagnosis
of the venous aneurysm was achieved by Doppler ultrasonography during the
evaluation for deep vein thrombosis. Venography showed a large fusiform aneurysm.
Both aneurysms were treated by resection and ligation. At follow-up, there was no
evidence of recurrent pulmonary embolism. These cases clearly illustrate the risk
of pulmonary embolism associated with uncommon localizations of venous aneurysms
and the potential for thrombus formation due to the venous stasis. Surgical
treatment, as in the case of popliteal aneurysms, is mandatory to avoid such
embolic complications.
PMID- 10192038
TI - [Are antiphospholipid antibodies thrombogenic in the course of human
immunodeficiency virus infection?].
AB - Lupus-like anticoagulant is commonly encountered in human immunodeficiency virus
infection although thromboembolic manifestations are rare in HIV patients. We
report the case of an HIV patient who developed gangrene of both forefeet
associated with anticardiolipin antibodies. A 42-year-old woman had a 12-year
history of HIV infection (stage B2). She presented with painful gangrene
involving the forefeet of 4-day duration. Doppler ultrasonography,
electromyography and nailfold capillaroscopy were normal. Skin biopsy revealed
intracapillary thrombi and severe necrosis within the hypodermis; there was no
evidence of vasculitis. Laboratory findings showed a marked inflammatory syndrome
and the presence of anticardiolipin antibodies (IgG: 22 GPL U/ml). Several
cutaneous manifestations are known to be associated with antiphospholipid
syndrome, such as livedo reticularis, ulcers and gangrene of the extremities.
Skin biopsy often shows noninflammatory thrombosis of small vessels within the
dermis. Microcirculation damages have also been described in HIV infection,
mainly vasculitis. In the present case report, the absence of both vasculitis and
other causes suggest that anticardiolipin could be the culprit. But, it is
possible that painful gangrene of the forefeet was secondary to HIV infection.
PMID- 10192039
TI - [How to provide practical treatment for ambulatory patients with deep venous
thrombosis].
AB - Much interest has been focused on low molecular weight heparins (LMWH), light
weight fragments of standard heparin, for the management of deep vein thrombosis
(DVT) without pulmonary embolism (PE). LMWHs offer several advantages:
predictable anticoagulant activity, better bioavailability, longer half-life,
better patient and caretaker comfort, safety and efficacy at least comparable to
continuous intravenous heparin. Ambulatory treatment is quite attractive and a
large number of patients with DVT are now being managed as outpatients. There are
however certain precautions which must be taken to avoid unsatisfactory
anticoagulation and subsequent consequences which have nevertheless been shown to
be exceptional in well-designed and well-conducted trials excluding patients with
high risk for hemorrhage and based on attentive medical control. The purpose of
this review is to propose clear and simple protocols for everyday practice aimed
at a global diagnostic and therapeutic management of venous thromboembolism. The
review of the literature draws attention to the need for confirmation of the
clinical suspicion of DVT, practical application of the anticoagulant treatment,
and the importance of the etiology search in order to avoid missing a congenital
or acquired state of thrombophilia or an occult cancer revealed by DVT. Half of
all cases of thrombosis are caused by these two etiologies. In addition, with the
development of noninvasive methods for diagnosing DVT, the efficacy of clear
therapeutic regimens and the simplification of coagulation tests warrant
outpatient management in many cases of DVT in compliance with certain rules of
good clinical practice: confirmation of the diagnosis and regular treatment
controls. An essential element is the close collaboration between the patient,
the physician, the nursing staff, the laboratory and the pharmacist.
PMID- 10192040
TI - [Early deep venous thrombosis after trauma to the distal leg: when to begin
prophylaxis in ambulatory patients?].
PMID- 10192042
TI - Quantitative imaging and statistical analysis of fluorescence in situ
hybridization (FISH) of Aureobasidium pullulans.
AB - Image and multifactorial statistical analyses were used to evaluate the intensity
of fluorescence signal from cells of three strains of A. pullulans and one strain
of Rhodosporidium toruloides, as an outgroup, hybridized with either a universal
or an A. pullulans 18S rRNA oligonucleotide probe in direct or indirect FISH
reactions. In general, type of fixation (paraformaldehyde or methanol-acetic
acid) had no apparent effect on cell integrity and minimal impact on
fluorescence. Permeabilization by enzyme treatment for various times, though
needed to admit high Mw detection reagents (avidin-FITC) in indirect FISH, tended
to nonspecifically degrade cells and lower the signal. Digestion was unnecessary
and undesirable for the directly labelled probes. Multilabelled (five fluorescein
molecules) probes enhanced fluorescence about fourfold over unilabelled probes.
Overall, direct FISH was preferable to indirect FISH and is recommended
especially for studies of microbes on natural substrata.
PMID- 10192041
TI - Reverse transcription polymerase chain reaction method for the detection of
glycopeptide resistance in enterococci.
AB - In this work we have developed reverse transcription polymerase chain reaction
(RT-PCR) methods for detecting specific mRNA from enterococci, particularly vanA
and vanB genes, responsible for glycopeptide resistance in this genus. mRNA from
the two genes was detected immediately after RNA extraction of a midlog phase
culture, determined by growth rate analysis. Because of the short half-life
associated with many bacterial RNA species (1.5-2 min), time is an important
factor in obtaining RNA of good yield and high purity. Our results showed that:
(i) the transcription of mRNA related to vanA ligase in enterococci showing Van A
phenotype happens only after induction with both vancomycin and teicoplanin; (ii)
the transcription of mRNA related to vanB ligase happens only in the presence of
vancomycin and (iii) there was no transcription of mRNA in the two strains
positive to vanA gene after PCR experiments. RT-PCR methodology can have numerous
applications in microbiology for studying gene expression in isolated bacteria
and also in nonculturable cells in environmental samples, for studies of
mechanisms and/or as an indicator of viability in bacterial communities.
PMID- 10192043
TI - Determination of polyhydroxyalkanoates in activated sludge by ion chromatographic
and enzymatic methods.
AB - Two new detection methods for the determination of poly-beta-hydroxybutyrate
(PHB) and -valerate (PHV) are described. Both methods are based on
depolymerization of PHB/PHV to 3-hydroxybutyrate (3HB) and 3-hydroxyvalerate
(3HV). Depolymerization was achieved by either propanolic or hydrolytic
digestion. Propanolic digestion transformed commercial PHB/PHV stoichiometrically
into 3HB/3HV and yielded apparently complete recoveries of bacterial PHB/PHV from
activated sludge. Hydrolytic digestion was suitable only for PHB determination.
For quantification of 3HB and 3HV directly from digested sludge, a method based
on ion-exchange chromatography and conductivity detection was developed (IC
method). Alternatively, the total of 3HB and 3HV was quantified using a
commercial enzymatic test kit and colorimetric detection (enzyme method). Both
detection methods are easier to perform than previous methods and are suitable
for complex matrices such as activated sludge. The IC-method is recommended for
high sample throughputs or if distinction between PHB and PHV is essential.
Enzymatic detection is recommended if a few samples per day have to be measured
immediately or if an ion chromatograph is unavailable.
PMID- 10192044
TI - Ethidium bromide: a fast fluorescent staining procedure for the detection of
symbiotic partnership of flagellates and prokaryotes.
AB - The hindgut of 'lower' termites harbors a dense population of flagellates and
bacteria. The flagellates possess ecto- and endosymbiotic prokaryotes. Most of
them are hardly visible in the phase contrast microscope. Staining with the DNA
intercalating agent ethidium bromide visualizes the nuclei of the flagellates as
well as the ecto- and endosymbiotic bacteria as red objects. Furthermore, it is
possible to distinguish between endosymbiotic methanogens and other bacteria.
Following UV excitation, the blue-green autofluorescence of the methanogenic
bacteria eclipses the red fluorescence light of the intercalated ethidium
bromide. The dye facilitates the observation of symbiotic bacteria and helps
identify the number, shape, localization, and dividing status of the nuclei.
Thus, it is a powerful tool for the examination of microorganisms in complex
habitats, which are rich in strongly autofluorescent material, like wood.
PMID- 10192045
TI - Rapid isolation of genes from an indexed genomic library of C. cinereus in a
novel pab1+ cosmid.
AB - In this study we present an indexed genomic library of homokaryon AmutBmut
constructed within a novel cosmid carrying pab1+ as a selectable Coprinus marker.
The average insert size per cosmid comprises 41 kb. We screened the library and
detected copies of known (a1-2, beta-tub, cgl1, ras, trp1) and of new Coprinus
genes (cac, lac1, lac2, lac3). Screening was performed either by Southern blot
hybridisation or more efficiently by non-radioactive PCR amplification. We
successfully applied PCR with specific and with degenerate primers, multiplex PCR
and colony PCR in library screening. Our results suggest a new, more efficient
pooling strategy for future high throughput screenings to be used in PCR with
pooled cosmid DNAs, or in a less laborious approach using pooled Escherichia coli
colonies for PCR.
PMID- 10192046
TI - Production and characterization of anti-peptide monoclonal antibodies with
specificity for staphylococcal enterotoxins A and B.
AB - A synthetic peptide containing selected epitopes from staphylococcal enterotoxin
A (SEA) and enterotoxin B (SEB) was used to produce monoclonal antibodies (Mabs)
to respective enterotoxins in a single fusion procedure. The peptide inhibited
the reaction of polyclonal anti-SEA or anti-SEB antisera with their homologous
enterotoxin, thus showing that the chosen epitopes are part of the antibody
inducing enterotoxin sequences. Two Mabs, Mab-A and Mab-B, reacted with both the
peptide and with either SEA or SEB. Used in a double antibody sandwich ELISA, the
Mabs were able to quantitate the native SEA or SEB toxins at nanogram levels.
PMID- 10192047
TI - High purity 14CH4 generation using the thermophilic acetotrophic methanogen
Methanothrix sp. strain CALS-1.
AB - Methane-oxidizing activity in natural samples is typically measured by amending
14CH4 to the sample and then following the accumulation of 14CO2. Current
biological techniques to synthesize 14CH4 yield significant quantities of 14CO
that when oxidized to 14CO2 would artificially inflate the measured methane
oxidizing activity of a sample. We present here a new method to biologically
produce highly-pure 14CH4 using Methanothrix sp. Strain CALS-1 which produces
very little CO. Using this method, 14CH4 was produced at nearly 100% efficiency
and at a high specific activity (2.2 GBq.mmol-1) equal to the parent compound, [2
14C] sodium acetate. Furthermore, only trace quantities of H2 and CO were
produced with only one molecule of CO produced for every 17,000 molecules of CH4.
When compared to the standard CH4 generation method, this technique produced 97%
purer CH4.
PMID- 10192048
TI - Estimating microbial population counts by 'most probable number' using Microsoft
Excel.
AB - A computer-assisted method for determining population counts using the 'most
probable number' (MPN) was developed. The Microsoft Excel spreadsheet and its
Solver tool were used to generate MPNs, error estimates and confidence limits.
Our method was flexible, allowing the use of unbalanced replication schemes and
varying replication numbers and inoculation volumes. Furthermore, it required no
programming skills and generated fast results, which were comparable to those of
standard MPN tables and MPN software.
PMID- 10192049
TI - An alternative inverse PCR (IPCR) method to amplify DNA sequences flanking Tn5
transposon insertions.
AB - We have developed an alternative method to amplify DNA sequences flanking Tn5
transposon insertions. This method relies on the identical sequences of inverted
terminal repeats, located at the 5' and 3' ends of Tn5, to determine the location
and orientation of a transposon insertion within a restriction endonuclease
fragment. From this information, PCR primers can be designed to selectively
amplify by inverse PCR the DNA flanking one side of the transposon. This method
avoids the problem of amplifying or cloning long sequences flanking Tn5. To
demonstrate the applicability of this method, we generated Tn5 transposon mutants
of Pseudomonas abietaniphila BKME-9 which no longer grew on dehydroabietic acid
(DhA). The flanking sequence of one of the mutant (strain BKME-941) which
accumulated 7-oxoDhA, was amplified.
PMID- 10192050
TI - Uptake kinetics of nucleic acid targeting dyes in S. aureus, E. faecalis and B.
cereus: a flow cytometric study.
AB - For flow cytometry-based detection as well as susceptibility testing and
counting, staining of the bacterial cells is essential. In an attempt to develop
rapid preparatory procedures for nucleic acid staining of wild type Gram positive
bacteria, the uptake of fluorescent dyes in viable S. aureus, E. faecalis, and B.
cereus cells was studied by flow cytometry under conditions intended to block
probe efflux and increase cell wall permeability. The aim of the study was to
develop procedures which allow rapid nucleic acid staining independent of
fixation, since ethanol fixation is time-consuming and may mask phenomena
associated with viability and lead to uncontrolled loss and aggregation of cells.
The dye uptake was measured repeatedly after treating cells with metabolic
inhibitors in order to block probe efflux, or cold shock (0 degree C) to increase
permeability. The probes used were mithramycin (Mi), ethidium bromide (EB), DAPI,
Hoechst 33342 and Hoechst 33258. None of the procedures facilitated uptake of the
dyes to a level similar to that obtained in fixed control cells in all of the
species. After metabolic inhibition of B. cereus cells, DAPI and Hoechst
fluorescence increased to a level similar to or above that found in fixed cells,
indicating that the uptake of these dyes is limited by energy-dependent efflux. A
similar increase of DAPI fluorescence was observed after cold shock suggesting
the uptake of this dye to be limited also by permeability in B. cereus. The Mi
and EB fluorescence increased to the level of the fixed control cells under all
conditions tested, suggesting free probe influx in this species. Generally, probe
uptake in S. aureus and E. faecalis was lower than in B. cereus cells, and no
permeabilizing effect of cold shock was observed. In some experiments the
fluorescence exceeded that of ethanol fixed control cells, indicating that the
fixation may cause conformational changes in DNA.
PMID- 10192051
TI - Preservation of some extremely thermophilic chemolithoautotrophic bacteria by
deep-freezing and liquid-drying methods.
AB - Long-term preservation methods for extreme thermophilic chemolithoautotrophic
bacteria representing various species are described. The cultures were
cryopreserved in liquid nitrogen under anaerobic conditions using 5%
dimethylsulfoxide as a cryoprotectant. For easy storage and transport, the
cultures were successfully liquid-dried, directly from the liquid phase without
involving freezing under semiaerobic conditions using effective protective agents
such as ethylenediamine and meso-inositol. The tested cultures showed good
stability and survival rates after drying, after cryopreservation and on long
term storage. All tested strains were successfully preserved and reactivated
within relatively short time. The viability, stability and ability of
chemolithoautotrophic growth was not affected. Cryopreservation, liquid-drying
and reactivation under microaerobic conditions proved very effective for these
oxygen sensitive cultures.
PMID- 10192052
TI - Soft cervical disc herniation. An analysis of 187 cases.
AB - METHODS: During the period from January 1986 to December 1994, 187 consecutive
patients (102 males and 85 females, between the ages of 24 and 63 years) with
soft disc herniations of the cervical spine were operated on by anterior
approach. RESULTS: One hundred and twenty-seven (67.9%) patients presented pure
radicular syndrome, 17 (9.1%) with pure medullary syndrome, and 43 (23%) with
myeloradiculopathy. Disc herniation was at the C3/4 level in 8 (4.3%) cases, at
the C4/5 level in 17 (9.1%) cases, at the C5/6 level in 101 (54%) cases, and at
the C6/7 level in 87 (46.6%) cases. In 18 (30%) patients suffering from
myelopathy (with or without radiculopathy) an area of high MR signal intensity
was observed within the cervical cord on T2-weighted images; such area
corresponded at the level of cord compression by the herniated disc and was not
demonstrated on T1-weighted images. All patients underwent microdiscectomy
without bone grafting. Complete or almost complete relief of preoperative
symptomatology was observed in 95.6% of patients with radiculopathy and in 83.3%
of those with myelopathy.
PMID- 10192053
TI - A study on hemostasis parameters in the neurosurgery of cerebral aneurysms.
AB - BACKGROUND: This prospective study was accomplished with 14 patients, 10 women
and 4 men, where some pre-, intra- and immediate postoperative parameters of
hemostasis were analyzed and compared to a control group of normal individuals.
METHODS: The patients included in this study were admitted to the Hospital das
Clinicas at Unicamp in the 1990-1993 period. All the accepted patients have had
their latest bleeding at least 30 days before surgery, therefore, after the acute
bleeding phase, because in this phase there are alterations in hemostasis. In
this period only dipyrone was used in all patients as analgesics and
antipyretics. Opiates were used in all the anesthetic proceedings. The following
parameters were determined: coagulation; prothrombin time, (PT), thrombin time,
(TT), activated partial thromboplastin time, (APTT), platelets (PQ), fibrinogen,
(FG) factor V, (F V), protein C, (P C), protein S (PS), antithrombin III (AT
III); fibrinolysis, plasminogen (PLG), C 1 inhibitor (C 1), alfa 2 macroglobulin
(A2M), prekallikrein (PK), euglobulin lysis time (ELT), lysis area in fibrin
plates (LAFP), in 5 of these 14 patients. Activity of both plasminogen tissue
activator (t-PA) and plasminogen activator inhibitor (PAI-1) were also
determined. For analyze the hepatic function pre-albumin (PRE ALB) was
determined. RESULTS AND CONCLUSIONS: In this study, the analysis of LAFP and ELT
in the different surgical times suggests that the patients submitted to cerebral
aneurysm surgery are head to hypofibrinolysis from the intraoperative to the
immediate postoperative period and this evidence do not related whit PAI-1.
PMID- 10192054
TI - Provision of a neuroendoscopy service. The Southampton experience.
AB - BACKGROUND: A series of 21 patients (aged 1 week to 80 years) underwent a total
of 22 neuroendoscopic procedures in our Unit in the period July 1993 to January
1996. METHODS: The procedures were performed by one surgeon familiar with the
technique using the Stortz rigid neuroendoscope system. The most common
indication for neuroendoscopy was obstructive hydrocephalus. The most frequently
performed procedure was third ventriculostomy and tumor biopsy. The intended
surgical procedure was successfully performed in all but two of the cases
(attempted septostomy and internal cyst drainage) were both abandoned due to
unrecognisable anatomy. RESULTS: Of the 19 patients treated by fenestration or
ventriculostomy to relieve hydrocephalus, 5 eventually required definitive
shunting procedures. CONCLUSIONS: Complications relating directly to the
neuroendoscopy occurred in 2 patients (bleeding requiring temporary external
ventricular drain) and there were no surgical deaths.
PMID- 10192055
TI - Subtemporal suboccipital transpetrosal transsigmoidal approach to aneurysm of the
basilar artery fenestration.
AB - The aneurysm arising from the lower third of a basilar artery fenestration is a
rare event. The traditional suboccipital or subtentorial transtentorial or
transoral approach to this vascular malformation can be problematic. We report
the case of a 52-year-old woman who suffered a Grade 4 subarachnoid hemorrhage
from an aneurysm located at a fenestration of the proximal third of the basilar
artery. This aneurysm was successfully clipped through a left subtemporal
suboccipital translabyrinthine transsigmoidal approach. In the aneurysms of the
proximal third of the basilar artery the transpetrosal approach with its variants
(translabyrinthine and transsigmoidal) related to patient's clinical condition
can be useful with undoubted advantages.
PMID- 10192056
TI - Atypical pleomorphic xanthoastrocytoma.
AB - A 65-year-old man experienced an ictal episode. CT revealed a left capsulo
thalamic mass, and SPET showed hypoperfusion of the left cerebral emisphere. The
lesion was subtotally removed, and postoperative radiotherapy was given.
Pathological examination demonstrated an "atypical" pleomorphic
xanthoastrocytoma. The patient died of massive regrowth of the tumor 22 months
after surgery. This case is discussed in light of the pertinent literature.
PMID- 10192057
TI - Intracranial myxoid chondrosarcoma with early intradural growth.
AB - Chondrosarcomas are extremely rare intracranial cartilaginous tumors of which the
myxoid variant is the least reported in the literature. They develop extradurally
and generally infiltrate the dura only in advanced stages or at recurrence. We
describe the case of a 55-year-old woman with a posterior cranial fossa myxoid
chondrosarcoma which had a primarily intradural extension.
PMID- 10192058
TI - Actinomycosis of the central nervous system: surgical treatment of three cases.
AB - Three cases of actinomycotic brain infection are described, 2 of which manifested
as cerebral abscess, the third as epidural empyema. Complete resolution of the
infection was always achieved by means of surgical treatment and prolonged
antibiotic therapy. The cases reported emphasize the importance of a combined
approach in the treatment of this unusual cause of brain infection.
PMID- 10192059
TI - Periventricular hydatid cyst.
AB - Periventricular localization of hydatid cyst is very rarely seen. A 5-year-old
boy with periventricular hydatid cyst is presented. He had right hemiparesis and
focal seizures. Computerized tomographic scan showed a hydatid cyst in the left
periventricular area. Hydatid cyst was successfully removed. The postoperative
course was uneventful.
PMID- 10192061
TI - Improving door-to-needle time for thrombolysis in acute myocardial infarction.
PMID- 10192062
TI - Coronary artery disease: new epidemiological insights.
PMID- 10192060
TI - Transient oculomotor cranial nerves palsy in spontaneous intracranial
hypotension.
AB - Transient sixth cranial nerves palsy may occur in rare cases after lumbar
puncture, spinal anesthesia and myelography as well as in more rare cases of
spontaneous intracranial hypotension. We report three cases of spontaneous
intracranial hypotension with sixth cranial nerves palsy. One of these patients
presented also third cranial nerve palsy, never reported in spontaneous
intracranial hypotension.
PMID- 10192063
TI - Magnetic resonance imaging in cardiology.
PMID- 10192064
TI - Echocardiography.
PMID- 10192065
TI - Management of heart failure.
PMID- 10192066
TI - Prescribing for obesity. Comment on the Royal College of Physicians' Working
Party report on clinical management of overweight and obese patients with
particular reference to drugs.
AB - Physicians are reluctant to treat obesity despite the rapid increase in its
prevalence in the UK and its associated health problems such as diabetes,
coronary heart disease and hypertension. Overweight and obesity are chronic
conditions that require long-term treatment. Any therapeutic programme should
combine dietary restriction with physical activity and alterations to lifestyle.
The use of pharmacological treatment as an adjunct to conventional treatment
modalities is justified in certain circumstances. The criteria applied for the
prescription of an anti-obesity drug should be comparable to that applied to the
treatment of other relapsing disorders. The objective of the Royal College of
Physicians' new report, Clinical management of overweight and obese patients with
particular reference to the use of drugs, is the provision of such necessary
guidance. Based on evidence from clinical trials, the recommendations of the
report utilise a 12-week goal (outside a drug trial) of 5% body weight loss from
the start of drug treatment. Failure to achieve this goal is an indication for
stopping drug therapy. Safety and efficacy demand appropriate use of anti-obesity
drugs in a supervised setting with clinicians weighing up likely medical benefit
against possible risks.
PMID- 10192067
TI - The ideology of 'accountability'.
PMID- 10192068
TI - Towards a broader agenda for training in critical appraisal.
AB - Much progress has been made in recent years towards an evidence-based approach to
health care, i.e. the routine framing of an explicit decision sequence in the
clinical encounter, the systematic search for published evidence, and the
appraisal of relevant research articles. We argue that this is a commendable but
limited milestone, and that training in evidence-based health care, particularly
the use of critical appraisal techniques, is in need of a broader agenda. We
outline a proposal through which the skills and attitudes needed for the critical
appraisal of published articles may be applied to all other aspects of clinical
practice, from planning research projects to presenting results and guidelines
and peer review of articles submitted for publication.
PMID- 10192069
TI - Giving or withholding fluid and nutrients: ethical and legal aspects.
AB - When a patient does not or cannot drink or eat enough to maintain adequate
hydration or nutrition, fluid with or without nutrients can be given through a
tube. In law, a tube feed for an adult is regarded as a medical treatment that
can be refused, withheld or withdrawn. Legal requirements and ethical principles
of conduct are discussed in relation to a patient's ability or wish to drink and
eat, and the administration of fluid with or without nutrients by tube. Emphasis
is placed on adequate consultation from the outset with each competent patient,
between all members of the health care team, and with those closest to an
incompetent patient.
PMID- 10192070
TI - Effectiveness of a 'thrombolysis nurse' in shortening delay to thrombolysis in
acute myocardial infarction.
AB - OBJECTIVES: To determine whether a specialist cardiac nurse would improve delay
to thrombolysis in acute myocardial infarction (MI). SUBJECTS: Patients
presenting with chest pain to a district general hospital. METHOD: Comparison of:
a) door-to-needle times of patients with 'definite' MI when the nurse was on and
off duty (15 months) and prior to her employment (3 months); b) pain-to-needle
times for definite MI; and c) door-to-needle times of patients without definite
MI on first electrocardiogram (ECG) but who subsequently qualified for
thrombolysis. RESULTS: Of 365 patients included in the study, 289 had definite
MI. Before the appointment of a thrombolysis nurse, door-to-needle times were 0%
at 30 minutes, 7% at 45 minutes and 34% at 60 minutes. Since the appointment,
with the nurse on-duty, they have improved to 58%, 91% and 100% respectively, a
saving of 36 minutes in median door-to-needle time (p = 0.0001). There was a
median saving of 95 minutes in pain-to-needle times with the thrombolysis nurse
on duty compared with off duty (p = 0.0001). Finally, with the nurse on duty
there was also a saving of 36 minutes in median door-to-needle time in patients
in whom the first ECG was non-diagnostic for MI (p = 0.02). CONCLUSIONS: A
thrombolysis nurse produced a dramatic improvement in median door-to-needle and
pain-to-needle times in patients presenting with definite MI. This would lead to
an additional 41 lives saved at 30 months per 1,000 patients treated. With 24
hour thrombolysis nurse cover, this would potentially lead to 8 additional lives
saved at 30 months at a cost of 12,300 Pounds each. There was also a striking
improvement in door-to-needle times for patients presenting with a non-diagnostic
first ECG who subsequently qualified for thrombolysis.
PMID- 10192071
TI - No harm done? Psychological assessment in the A&E department of patients who
deliberately harm themselves.
AB - OBJECTIVE: To determine whether psychosocial assessments of patients presenting
to the Accident and Emergency (A&E) Department at Addenbrooke's Hospital,
Cambridge, with deliberate self-harm are recorded adequately in the case notes,
using the criteria of the 1994 Royal College of Psychiatrists' consensus
statement on managing adult deliberate self-harm in hospital. DESIGN: A cross
sectional study of case notes. SUBJECTS: A total of 338 patients (accounting for
404 episodes of deliberate self-harm) who presented consecutively between 1
January and 30 June 1996. RESULTS: 56% of episodes resulted in admission to a
general hospital bed. In only 11% of conscious patients were adequate
psychological assessments recorded in the case notes. Little psychosocial
information was recorded in the notes of those patients discharged without follow
up from accident and emergency. CONCLUSIONS: In the A&E department of this
teaching hospital, there is inadequate recording of important psychological
information in the case notes of patients who present with deliberate self-harm.
PMID- 10192072
TI - Clinical training of specialist registrars in neurology: the registrar's
perspective.
AB - OBJECTIVES: To find out how closely consultants supervise specialist neurology
registrars in different clinical settings (acute admissions, routine admissions,
ward referrals, new outpatients and old outpatients) and how much registrars
value this supervision. DESIGN: Questionnaire asked: how often clinical
assessments were done (from 'not done' to 'almost always'); how useful these were
for training (from 'not useful' to 'very useful'). SUBJECTS: Distributed via
regional education supervisors to registrars in their region. RESULTS: Sixty-one
responses from 88 distributed questionnaires (69%). Acute admissions were closely
supervised (> 80%) and valued as training. Routine admissions and ward referrals
were less frequently reviewed, though review was valued. New outpatients were
reviewed 'infrequently' or 'not at all' in 65%, though review was valued for
training (> 80%). Old outpatients were less frequently reviewed but this was less
valued. CONCLUSIONS: Inpatient supervision of neurology trainees is close and
valued by trainees, though review of ward referrals is often a missed opportunity
for training. Outpatient supervision is limited, though highly valued by
trainees. Time needs to be made available within the outpatient clinic to allow
supervision and training.
PMID- 10192073
TI - Immunotherapy.
AB - A forward looking conference took place at the Royal College of Physicians in
June 1998. The audience, which included many scientific and clinical
immunologists from both the university and pharmaceutical sector, participated
knowledgeably and critically in the discussions on possible future treatments for
immunologically caused diseases and on the scientific principles which may bring
about further developments in immunotherapy.
PMID- 10192074
TI - Why do we need Royal Colleges?
AB - Today's Royal Colleges can be traced to the guilds that arose during the 13th and
14th centuries. They fulfil similar roles: to maintain the highest standards of
practice, professional integrity and self-regulation. This paper traces the
development of the Royal Colleges, together with the emergence of specialisation
within medicine, with particular reference to anaesthesia as a modern specialty.
It considers whether these functions are still appropriate for the rapidly
changing practice of medicine today. The colleges have unique strengths, but they
also have weaknesses and must be prepared to counter threats to their
professional function.
PMID- 10192075
TI - Equality of health: dream or reality?
PMID- 10192076
TI - Three journeys to high altitude: medicine, Tibetan thangkas, and Sepu Kangri.
AB - This article begins by highlighting the work of several pioneers of altitude
medicine, and their achievements in physiology and clinical observation. Tibetan
medicine of the 17th century is then introduced, particularly the medical
paintings (thangkas) and the conduct of traditional physicians. Finally, I
mention recent British mountain exploration in central Tibet during 1996, 1997
and 1998 and the challenge of Sepu Kangri which, at 6,995m, is the highest peak
of the eastern Nyangla Qen Tangla Shan.
PMID- 10192077
TI - When a cane was the necessary complement of a physician.
AB - Although Dr John Radcliffe's gold-headed cane, presented to the Royal College of
Physicians in 1825, became well-known following the publication two years later
of Dr William Macmichael's book, The gold-headed cane, little consideration has
previously been given either to medical canes, or to the custom of cane-carrying
by doctors in the 18th century. This article makes a brief assessment of medical
canes within the social and historical framework of the period, and views
Macmichael's book in its literary context, with mention of other relevant
examples of books in this genre.
PMID- 10192078
TI - An open letter to the Director General of the Cancer Research Campaign.
PMID- 10192079
TI - Telemedicine and the undergraduate medical curriculum.
PMID- 10192080
TI - Sympathy towards patients.
PMID- 10192081
TI - Nuclear cardiology.
PMID- 10192082
TI - Chylothorax in a cat.
PMID- 10192083
TI - Versternema struthionis in ostriches: is there an association with peritonitis?
PMID- 10192084
TI - Genetic analysis of three South African horse breeds.
AB - Genetic variability at 7 blood-group and 10 biochemical genetic loci was examined
in 3 South African horse breeds, the Nooitgedacht, Boerperd and Basuto Pony.
Observed heterozygosity for these breeds was intermediate for domestic horses,
with the highest heterozygosity in the Boerperd and the lowest in the Basuto
Pony. The 3 breeds show greater genetic similarity to each other than to other
domestic horse breeds. Compared to other breeds, the South African breeds show
greater genetic similarity to breeds such as the Thoroughbred, Holstein,
Trakehner and Hanovarian and also to North American breeds such as the
Saddlebred, Standardbred and Morgan Horse.
PMID- 10192085
TI - Serological survey for antibodies reactive with Ehrlichia canis and E.
chaffeensis in dogs from the Bloemfontein area, South Africa.
AB - Sera from 161 dogs in the Bloemfontein area in South Africa were tested for the
presence of antibodies reactive with Ehrlichia canis and E. chaffeensis by
indirect fluorescent antibody testing. Overall, 68 (42%) of the dogs had
significant antibody titres (> or = 1/64) against E. canis and 61 (38%) had
significant titres (> or = 1/64) against E. chaffeensis. Seven (11%) dogs had
higher titres to E. chaffeensis than E. canis (1/2048 and 1/1024 (2 dogs); 1/1024
and 1/512 (2 dogs); 1/2048 and 1/512; 1/512 and 1/256 and 1/512 and < 1/64,
respectively). The remaining seropositive dogs had equal (n = 26; 42%) or 2-(n =
17; 25%), 3-(n = 13; 2%) or 4-fold (n = 5; 7%) higher titres against E. canis.
Dogs from economically depressed, high-density suburbs (60/112; 48%) had
significantly higher prevalences of antibodies against E. canis than those from
more affluent, low-density suburbs (8/49; 14%) (chi 2 = 19.38, p < 0.001). Higher
titres to E. chaffeensis than E. canis were found in dogs from affluent, low
density suburbs (3/49) and in dogs from economically depressed, high-density
suburbs (4/112).
PMID- 10192086
TI - Treatment of heartwater: potential adverse effects of furosemide administration
on certain homeostatic parameters in normal sheep.
AB - Diuretics, in particular furosemide, are generally recommended as a supportive
treatment in the advanced stages of heartwater in ruminants. However, after what
appeared to be possible adverse effects accompanying its use in field cases of
heartwater, the effects of this drug on certain blood and urine parameters were
investigated in normal sheep at the same dose rates. Diuresis with concomitant
natriuresis was significant after furosemide administration, as was the expected
plasma volume decrease. Other significant changes included metabolic alkalosis,
hypokalaemia and reduced blood ionised calcium. The difference in duration of the
diuretic effect and the duration of the changes in blood parameters from c. 3 h
and c. 6 h respectively make it difficult to determine a time interval between
successive treatments with furosemide. It appears that the probable cause of
death of sheep with heartwater is a drastic reduction in blood volume and
decreased cardiac output that leads to general circulatory failure. A therapeutic
approach that involves further loss of plasma volume due to diuresis appears
contradictory. The added effects of potentiating respiratory alkalosis and the
terminal drop in blood ionised calcium seen in heartwater-affected animals
indicate that the use of furosemide in supportive treatment of this disease is
not warranted.
PMID- 10192087
TI - Perioperative plasma cortisol concentration in the horse.
AB - The cortisol response to anaesthesia and surgery was studied in 2 groups of
horses undergoing either abdominal or non-abdominal surgery. The preoperative
mean plasma cortisol concentration (pcc) of 381.7 nmol/l (s.d. 254.7) was
markedly higher in the abdominal group than the early-morning mean pcc of 115.6
nmol/l (s.d. 78.4) in the non-abdominal group. During halothane anaesthesia and
surgery the mean pcc increased significantly (p < 0.05) from the preoperative
mean of 119.2 to 215.9 nmol/l (s.d. 79.8) after 30 min of surgery in the non
abdominal group. In the abdominal group a decrease occurred after induction of
anaesthesia and surgical preparation, but increased during surgery to a mean pcc
of 418.1 nmol/l (s.d. 236.5). In the postoperative period a large decrease in the
mean pcc occurred after 24 h in the abdominal group. It was only after 60 h that
the pcc (153.2 nmol/l) equalled the pcc of the non-abdominal group (171.4 nmol/l)
at 24 h. The slow decline over 60 h could be an indication of the prolonged
recovery associated with abdominal surgery in the horse.
PMID- 10192088
TI - The effect of dietary protein on reproduction in the mare. VI. Serum progestagen
concentrations during pregnancy.
AB - Sixty-four Thoroughbred and Anglo-Arab mares aged 6-12 years were used, of which
40 were non-lactating and 24 lactating. Foals from these 24 mares were weaned at
the age of 6 months. Non-lactating and lactating mares were divided into 4
dietary groups each. The total daily protein intake and the protein quality
(essential amino-acid content) differed in the 4 groups of non-lactating and 4
groups of lactating mares. The mares were covered and the effect of the quantity
and quality of dietary protein on serum progestagen concentrations during
pregnancy was studied. A sharp decline in serum progestagen concentrations was
recorded in all dietary groups from Days 18 to 40 of pregnancy, with some
individual mares reaching values of less than 4 ng/ml. Serum progestagen
concentrations recorded in some of the non-lactating mares on the low-quality
protein diet increased to higher values (p < 0.05) than those of mares in the
other 3 dietary groups at 35-140 days of pregnancy. A similar trend was observed
for the lactating mares on a low-quality protein diet at 30-84 days of pregnancy.
No such trends were observed in any of the other dietary groups. High-quality
protein supplementation increased serum progestagen concentrations during the 1st
30 days of pregnancy. Lactation depressed serum progestagen concentrations until
after the foals were weaned.
PMID- 10192089
TI - The effect of dietary protein on reproduction in the mare. VII. Embryonic
development, early embryonic death, foetal losses and their relationship with
serum progestagen.
AB - Sixty-four Thoroughbred and Anglo-Arab mares aged 6-12 years were randomly
allocated to 4 dietary groups and fed diets that differed in the total protein
content and quality (essential amino-acids). Forty mares were non-lactating and
24 lactating. Eight mares were withdrawn from the investigation owing to injuries
or gynaecological pathology. An overall conception rate of 94.6% and a foaling
rate of 80% was achieved. Five of 14 (35.7%) mares (Group 1) fed a low-quality
protein diet suffered from early embryonic loss before 90 days of pregnancy
compared to 3 of 41 (7.3%) mares in the remaining groups that received the higher
quality protein in their diets. Serum progestagen concentrations of mares in
Group 1 that suffered foetal loss were indicative of luteal function
insufficiency during the 1st 40 days post-ovulation. Non-lactating mares in all 4
groups gained on average approximately 30 kg in mass during the 90 days before
the breeding period. Lactating mares in Group 1 (low-quality protein) lost on
average 25 kg in mass during lactation, with no weight loss observed among the
lactating mares in the other 3 groups. No difference in the diameter of the
embryonic vesicle was found between dietary groups until Day 35 of pregnancy.
PMID- 10192090
TI - Clinico-pathological studies in cattle experimentally infected with Taenia
saginata eggs.
AB - Calves 1-2 months old were experimentally infected with eggs of Taenia saginata
and clinical and haematological deviations, development and distribution of
cysticerci and pathological changes were recorded. The calves infected with
5,000, 10,000 or 50,000 eggs showed an increase in pulse and respiratory rates.
The animals that received 50,000 eggs had significantly increased pulse (p <
0.05) and respiratory rates (p < 0.005). The symptoms were more severe in young,
30-day-old calves infected with 50,000 eggs. Haemoglobin concentration,
haematocrit values and red blood cell count decreased, but white blood cell count
increased slightly. Lymphocytes and eosinophils also increased up to 88% and 14%
(p < 0.05), respectively. Most of the cysticerci were not fully formed 1 month
post-infection, but at 2 months the cysts were fully mature and at 4 months, some
cysts had degenerated. There was no uniform pattern of distribution of cysticerci
in the body of infected calves, but the most commonly affected sites were
masseter and heart muscles, followed by diaphragm, tongue and other skeletal
muscles. The maximum concentration of 8-14 cysticerci per 10 g of tissue was
recorded in masseter muscles and heart. The affected parts revealed tissue
reactions that included pressure atrophy, necrosis and fibrosis. Microscopically,
the lesions comprised infiltration with lymphocytes, plasma cells, eosinophils
and macrophages, fibrosis, necrosis and calcification. The tissue reaction was
severe in calves infected with 50,000 eggs. The severity of clinical signs,
haematological and pathological changes depended mostly on the age of the animals
and dose of infection.
PMID- 10192091
TI - Malignant fibrous histiocytoma of the deep peri-articular tissue of the stifle in
a dog.
AB - A Belgian shepherd dog aged 4 years and 9 months was presented with acute onset
of non-weight bearing lameness and stifle effusion of the left hind limb, caused
by the deep form of a malignant fibrous histiocytoma originating in the deep
musculature and fascia surrounding the stifle joint. The tumour progressed
rapidly in the tissues along the femoral diaphysis with marked periosteal new
bone formation. Cytology of a stifle joint aspirate revealed numerous large
polygonal neoplastic cells with considerable anisocytosis and anisokaryosis.
These cells were present in clusters, with cytoplasmic projections between the
cells, but occasionally also occurred singly. Several cells contained multiple
cytoplasmic vacuoles and occasional giant cells were also encountered. Adequate
tumour-free margins were not possible with radical limb amputation and the dog
was euthanased. Macroscopically the tumour appeared as an extensive pale tan,
firm mass with scattered small haemorrhages and foci of yellow discolouration.
Histologically the tumour consisted of dense neoplastic expanses or multiple
nodules, composed of spindle-shaped fibroblastic cells, polygonal histiocytic
cells or cell clusters and scattered giant cells with 2-3 nuclei. The polygonal
neoplastic cells were frequently present around and invading lymphatics and blood
vessels, causing neoplastic emboli. This is the 1st report of the clinical
behaviour, radiography and cytology of the deep form of malignant fibrous
histiocytoma in the dog.
PMID- 10192092
TI - Mokola virus infection: description of recent South African cases and a review of
the virus epidemiology.
AB - Five cases of Mokola virus, a lyssavirus related to rabies, are described. The
cases occurred in cats from the East London, Pinetown and Pietermaritzburg areas
of South Africa from February 1996 to February 1998. Each of the cats was
suspected of being rabid and their brains were submitted for laboratory
confirmation. Four of the cases were positive, but with atypical fluorescence,
and 1 was negative. Mokola virus infection was identified by anti-lyssavirus
nucleocapsid monoclonal antibody typing. As in rabies cases, the predominant
clinical signs were of unusual behaviour. Aggression was present, but only during
handling. Four of the 5 cats had been vaccinated for rabies, which is consistent
with other studies that show that rabies vaccination does not appear to protect
against Mokola virus. Since Mokola may be confused with rabies, the incidence of
Mokola virus may be more common in Africa than is currently reported. As human
infections may be fatal, the emergence of this virus is a potential threat to
public health.
PMID- 10192093
TI - Occurrence of dermatomycosis (ringworm) due to Trichophyton verrucosum in dairy
calves and its spread to animal attendants.
AB - Persistent dermatomycosis (ringworm) caused by Trichophyton verrucosum affected
20 dairy calves aged between 3 months and 1 year and housed together. The
infection also spread to 2 animal attendants working among the calves. The major
clinical lesions observed on the affected calves were extensive alopecia and/or
circumscribed thick hairless skin patches affecting the head, neck, flanks and
limbs. The observed lesions persisted for more than 17 weeks and most of the
calves did not respond to topical treatment with various anti-fungal drugs within
the anticipated period of 9 weeks. Two animal attendants developed skin lesions
that were circumscribed and itchy and there was good response to treatment
following the application of anti-fungal skin ointment. Although ringworm in
dairy animals in Kenya has not previously been associated with spread to humans,
the potential is evident from this report.
PMID- 10192094
TI - Antimicrobial selection, administration and dosage.
AB - Various types of information contribute to the selection of an antimicrobial
agent. Initial requirements are diagnosis of the site and nature of the
infection, assessment of the severity of the infectious process and medical
condition of the diseased animal; these are embodied in clinical experience.
Additional considerations include identification of the causative pathogenic
microorganism, knowledge of its susceptibility to antimicrobial agents
(microbiological considerations) and of the pharmacokinetic properties of the
drug of choice and alternative drugs, and their potential toxicity
(pharmacological considerations) in the animal species. Select an antimicrobial
drug and dosage form appropriate for use in the particular animal species. Usual
dosage regimens may be applied, except in the presence of renal or hepatic
impairment, when either modified dosage or a drug belonging to another class
should be used. The duration of therapy is determined by monitoring the response
both by clinical assessment and bacterial culture. A favourable clinical response
is the ultimate criterion of successful therapy.
PMID- 10192095
TI - Improvement of muscle protein functionality in processed meats by magnesium and
other divalent chloride salts.
AB - Concern over dietary fat in processed meats led to the passage of the '40 per
cent' rule in the United States. Substitution of NaCl, linked to hypertension,
with divalent chloride salts such as MgCl2 and CaCl2 has shown limited success.
Early studies showed that these divalent salts had a deleterious effect on the
functional properties of meat when used at product levels that resulted in high
aqueous phase ionic strengths (0.4-0.6). However, our research focus has been to
determine the utility of low levels (0.05 per cent) of MgCl2, CaCl2 and ZnCl2 in
improving the functional properties of processed meats. Effects of divalent salts
have been evaluated in turkey breast and thigh minces, beef model systems, and
frankfurter formulations containing heart muscle. To determine if time postmortem
affects muscle's response to divalent cations, salts were added to broiler thigh
muscle in the early postmortem period. The important findings were (1) MgCl2
increased myosin solubility, (2) CaCl2 enhanced gel forming ability in cooked
batters, and (3) ZnCl2 dramatically decreased myosin solubility in the absence of
food-grade phosphate (sodium tripolyphosphate).
PMID- 10192096
TI - Influence of low magnesium concentrations in the medium on the antioxidant system
in cultured human arterial endothelial cells.
AB - Using cultured human endothelial cells, we investigated the contribution of
concentrations of magnesium to the antioxidant system and oxidative stress. Cells
were cultured at decreasing magnesium levels (569, 380, 190 and 95 microM) for 72
h. We then measured the amount of released hydrogen peroxide (H2O2) from the
cells, the consumption of exogenous H2O2, the intracellular reduced glutathione
(GSH) and the oxidized glutathione (GSSG) contents and the activities of
glutathione reductase and catalase. Magnesium at a level of 949 microM was used
as a control. The effect of magnesium deficiency on cellular membrane
permeability was determined by measurement of the amount of [14C] amino acid
mixture released from the cells. The results showed that during 72 h of magnesium
deficient treatment, the H2O2 release from the cells gradually increased and
consumption of exogenous H2O2 was enhanced during the first 48 h of treatment.
GSH content gradually decreased but GSSG was not affected. The activity of
glutathione reductase was first stimulated and then inhibited. Catalase activity
was gradually reduced. [14C]Amino acid mixture release from the cells
continuously increased. We suggest that magnesium deficiency affected the
intracellular antioxidant system in cultured endothelial cells.
PMID- 10192097
TI - Effects of parenteral pharmacological magnesium loading on insulin secretion in
experimental thyrotoxicosis.
AB - Thyrotoxicosis is characterised by decreased magnesium pool and also insulin
resistance. The present study is evaluating the parameters of glucose metabolism
under pharmacological magnesium loading in experimentally induced thyrotoxicosis,
in rats. Insulin secretion was significantly increased in thyrotoxicosis compared
to controls, expressing probably the status of insulin resistance due to
thyroxine excess. After intraperitoneal magnesium infusion, plasma magnesium
reached pharmacologically high concentrations and insulin secretion decreased
significantly, but this decrease was not accompanied by alterations of glucose
homeostasis. In controls, we also found a tendency towards the decrease of
insulin secretion after magnesium loading, but it did not reach statistical
significance. Thus, insulin secretion seems more sensitive to the inhibitory
effects of magnesium overload in experimental thyrotoxicosis.
PMID- 10192098
TI - Importance of timing of magnesium administration: a study on the isolated
ischemic-reperfused rat heart.
AB - The present study attempted to explore the antioxidant potential of magnesium (2
and 10 mM) in the postischemic isolated rat heart. Magnesium demonstrated a
significant antioxidant effect, as deduced by thiobarbituric acid reactive
material and glutathione levels. However, this effect was evident only when
magnesium was administered prior to ischemia but not when administered during
reperfusion. On the other hand, attenuation of calcium accumulation following
reperfusion was noted in both treatment schedules and showed dose dependency when
administered during reperfusion. Thus, the results of this study strongly
suggests an antioxidant effect of magnesium which is distinct from its calcium
antagonising effects and it also stresses the critical role played by the time of
administration of magnesium.
PMID- 10192099
TI - In vitro effect of Cl2Ca and Cl2Mg on warfarin-human serum albumin (HSA) binding.
AB - The binding of warfarin to 10 mumol/L human serum albumin (HSA) was studied in
vitro by equilibrium dialysis in presence of two different calcium
concentrations. At 2.3 and 23 mmol/L calcium concentrations, the percentage
binding decreased. The number of saturable sites of warfarin-HSA at these two
calcium concentrations were 1.02 and 1.23 respectively; the number of saturables
sites observed with warfarin alone was higher (n1 = 1.32). The association
constant for saturable sites (K1 = 0.187 mumol-1) and the affinity coefficient
for the nonsaturable sites (n2K2 = 0.0955) remained unchanged. The binding to HSA
was 98 per cent at therapeutic levels, that is a physiological concentrations of
protein and therapeutic levels of warfarin, in the presence of several
concentrations of calcium (2.5; 5; 25; 50 and 100 mmol/L) or magnesium (1;2;10;50
and 100 mmol/L) as chloride compounds, the free fraction of warfarin remained
constant until calcium or magnesium reached concentrations of 50 mmol/L, in which
cases the percentage binding fell to 92 per cent. In conclusion a displacement of
bound warfarin can be expected only if the plasma concentrations of calcium or
magnesium and as well chloride concentration are raised by much.
PMID- 10192100
TI - Preliminary communication on intralymphocyte ionized magnesium in hypertensive
patients under treatment with beta-blockers.
AB - We measured free intralymphocyte magnesium (Mgi) in 10 hypertensive subjects (HS)
before and after treatment with atenolol (A) and in 16 normotensive control
subjects (NC). We also carried out in vitro studies on human lymphocytes to test
the effect of catecholamines and beta-antagonists on Mgi. Mgi in HS was not
statistically different before and after the treatment with A (M +/- SD, basal:
227 +/- 31 + mumol/l; A: 236 +/- 47 mumol/l; NS). Mgi in NC proved not
statistically different as compared to HS without treatment (M +/- SD, NC: 232 +/
35 mumol/l; HS before treatment: 227 +/- 31 mumol/l; NS). The Mgi of the
lymphocytes treated in vitro with noradrenaline (NA) significantly decreased in
comparison with the control (M +/- SD, basal: 244 +/- 26 mumol/l; NA: 198 +/- 25
mumol/l; p = 0.0001), whereas it did not change after incubation with NA and
propranolol (P) (M +/- SD, basal: 238 +/- 32 mumol/l; NA + P: 239 +/- 30 mumol/l;
NS). On the other hand Mgi decreased significantly after incubation with NA and A
(M +/- SD, basal: 255 +/- 21 mumol/l; NA + A: 202 +/- 34 mumol/l). Our in vivo
data show that the Mgi of HS remains unvaried after treatment with A, and that
there is not statistical difference between Mgi of NC and of HS before treatment.
The in vitro study demonstrated that catecholamines cause a significant reduction
in Mgi. This effect is only inhibited by a non-selective beta-blocker such as P.
These results seem to explain the ineffectiveness of treatment with atenolol on
our patients' Mgi.
PMID- 10192101
TI - Cardiovasoprotective foods and nutrients: possible importance of magnesium
intake.
AB - Various highly efficient cardiovasoprotective diets associate reduced intake of
total and saturated fats, reasonable supply of monounsaturated fat and omega-3
fatty acids, moderate consumption of alcohol, increased intake of cereals,
fruits, vegetables, fish and low fat dairy products. Among several protective
nutrients magnesium should be given particular consideration because of the very
frequent occurrence of chronic primary magnesium deficiency which appears to act
as a cardiovascular risk factor and also reversely, because of the noticeable
high level of the magnesium content in cardiovasoprotective diets.
PMID- 10192102
TI - Antitumor pyrido[3,2-d][1]benzazepines: synthesis and in vitro activity of
thiophene analogs.
AB - The bioisosteric replacement of benzene elements in the antitumor lead structures
2 and 3 led to the thienyl substituted 5H-pyrido[3,2-d][1]benzazepin-6(7H)-ones
8a and 8b, the analogous thiolactams 4a and 4b, and the 4H-pyrido[2,3-d]
thieno[3,2-b]azepines 11 and 12 which represent a novel heterocyclic scaffold.
The in vitro evaluation of 4a in a cell line based screening revealed a
noteworthy antitumor activity and a remarkable selectivity for renal tumor cell
lines. The cell line selectivity pattern of 4a differs distinctly from the
pattern displayed by standard antitumor agents.
PMID- 10192103
TI - [Synthesis, antimicrobial effects and adverse effects of new structures of urea,
hydrogen peroxide and tensides].
AB - A substantial extension of the applicability of hydrogen peroxide will be reached
by using occlusion compounds of anionic, amphoteric (dipolar ionic), cationic,
nonionic, or polyfunctional tensides with hydrogen peroxide in urea. Occlusion
compounds with 3 as well as with 4 components containing natural equivalent and
antimicrobial effective tensides were synthesized and tested. By synthesis in an
anhydrous system the content of active substances as well as the mixture ratio of
the components may be adapted to the conditions necessary according to the
appropriate purpose. Occlusion compounds are characterized by a broad and well
balanced spectrum of antimicrobial effectivity. Concentrations in the range of
0.1 to 0.4% are practicable to preserve pharmaceutical preparations or technical
products, respectively. Several compounds show a sporicidal activity in
concentrations between 0.3 and 0.6% and, with an appropriate action time (> 24 h)
also a moderate effectivity against polioviruses. In the conventional cell
culture, in the perfusion cell culture, and in the phytotoxicity test using cress
seed, respectively, low biological activity of the occlusion compounds was found.
PMID- 10192104
TI - Synthesis and reaction of cyanopyridone derivatives and their potential
biological activities.
AB - 4-Carboxy-3-cyano-6-biphenyl-pyrid-2-one (1) was prepared and then allowed to
react with methyliodide, benzenesulphonyl chloride, phenylisothiocyanate, acetic
anhydride, o-phenylenediamine, phenylmagnesium bromide and phosphorus
pentasulphide affording the corresponding N-substituted pyrid-2-one 2-5, 4
(benzimidazol-2-yl)-pyrid-2-one 7, 2-hydroxy-2-phenyl-1,2-dihydro-pyridine 8 and
2-thiopyridone 9 derivatives, respectively. Treatment of 1 with dimethyl sulphate
and phosphorus oxychloride to give 2-methoxy pyridine 12 and 2-chloro pyridine 13
derivatives. Reaction of 13 with amines and hydrazine hydrate afforded 14 and 15,
respectively. The structural assignments of the new compounds were based on
analytical, spectroscopic measurements and chemical reactions. Some of the
obtained compounds showed interesting antibacterial and antifungal activities in
vitro.
PMID- 10192105
TI - A spermine-deoxycholic acid conjugate based lipid as a transfecting agent.
AB - Deoxycholic acid-spermine conjugate (DAS), which is composed of natural
components (deoxycholic acid and spermine), was incorporated in liposomes and
evaluated for its interaction with plasmid DNA (pDNA) and in vitro transfection
efficiency. Electromicrographs demonstrated that DAS-pDNA complexes are
spherical, compact and electronically dense compared to the toroidal shapes
formed by the monovalent lipid 1,2-dioleoyl-3-trimethylammonium propane (DOTAP)
and pDNA. In comparison to the singly charged, non-cholesterol based lipid
(DOTAP), the multivalent lipid DAS had similar transfection efficiency in two
cell lines. The monovalent sterol, deoxycholic acid propyldiamine conjugate (DAP)
was not effective as a transfecting agent. This suggests that multivalent facial
amphiphiles such as DAS may serve as excellent candidates for non-viral gene
transfer and warrant further study.
PMID- 10192106
TI - Solid state stability of ketoprofen in the presence of different excipients.
AB - Physical mixtures of ketoprofen (KT) were prepared using different excipients,
namely, lactose, mannitol, sorbitol, beta-cyclodextrin, polyvinylpyrolidone (PVP)
K30, polyethyleneglycol (PEG) 20,000 and urea in a ratio of 2:1 (drug/excipient).
The prepared samples as well as KT alone were stored at 40, 50 and 60 degrees C
in sealed glass vials for 12 weeks. The fresh and stored samples were subjected
to physical examination and instrumental analysis including m.p., IR and
dissolution rate. KT without additives was found to be physically stable or when
mixed with either lactose, mannitol, sorbitol or beta-cyclodextrin for 12 weeks
at 60 degrees C. The m.p. of the drug alone or in presence of these excipients
did not change. Also IR showed no change. On the other hand, KT mixtures with PVP
K30, PEG 20,000 or urea were physically unstable on storage at 40, 50 and 60
degrees C. Their m.p. were found to decrease; the IR curves were also changed.
All the tested excipients enhanced the dissolution of KT from its physical
mixtures and could be arranged according to the extent of dissolution as follows:
Lactose = Mannitol > beta-cyclodextrin > PVP K30 = Urea > Sorbitol > PEG 20,000.
PMID- 10192107
TI - Inclusion complexation of furosemide in cyclodextrins. Part 2: Implication on
bioavailability.
AB - The effect of inclusion complexation of furosemide in cyclodextrins (CyD) on the
bioavailability of the drug was studied on normal human volunteers. The excretion
rate of the drug was determined by HPLC for a period of 24 h. post dosing.
Several pharmacokinetic parameters were calculated and statistically analyzed.
viz., peak excretion rate, peak excretion time, half peak time, elimination rate
constant, area under the excretion rate time-curve as well as the total amount of
drug excreted. The obtained results show that on administration of furosemide in
the form of an inclusion complex in CyDs particularly beta-CyD or its dimethyl
derivative may improve its biological performance, taking into consideration that
furosemide is characterized by a rapid onset and a short duration of action.
Inclusion complexation of furosemide in CyDs leads to a more or less delay in its
onset of action, a significant increase in its duration of action as well as
significant augmentation in its overall biological availability.
PMID- 10192108
TI - [Peppermint oil-caraway oil fixed combination in non-ulcer dyspepsia--comparison
of the effects of enteric preparations].
AB - 223 patients with non-ulcer dyspepsia (dysmotility type dyspepsia or
essential/idiopathic dyspepsia, also in combination with irritable bowel
syndrome) were included in a prospective, randomised, reference- and double-blind
controlled multicentre trial to compare two different preparations of a fixed
combination of peppermint oil and caraway oil. The aim of the trial was to
evaluate the equivalence of the efficacy and tolerability of these two
preparations. The test formulation consisted of the drug combination in an
enteric coated capsule containing 90 mg peppermint oil and 50 mg caraway oil,
while an enteric soluble formulation containing 36 mg peppermint oil and 20 mg
caraway oil was used as the reference. The main target item defined was the
"difference in pain intensity between the beginning and the end of therapy",
measured by the patient on a visual analogue scale (0 = no pain, 10 = extremely
strong pain). In 213 patients (n = 108 on the test preparation, n = 105 on the
reference preparation) with mean pain intensity baseline measurements of 6.1
points in the test preparation group and 5.9 points in the reference group a
statistically significant decline in pain intensity was observed in the two
groups (-3.6 resP. -3.3 points; p < 0.001; two-sided one-sample t-test).
Equivalent efficacy of both preparations was demonstrated (p < 0.001; one-sided t
test for equivalence). With respect to concomitant variables, the results in both
groups were also similar. Regarding "pain frequency", the efficacy of the test
preparation was significantly better (p = 0.04; two-sided t-test for difference).
Both preparations were well tolerated. Despite the higher dose, the adverse event
"eructation with peppermint taste" was less frequent in the group treated with
the test formulation, due to the enteric coated capsule preparation.
PMID- 10192109
TI - In vitro cytotoxic activity of naphtho[1,2-b]furan, furo[2,3-f], furo[2,3-g] and
furo[3,2-g]quinoline derivatives.
AB - Some naphtho[1,2-b]furan, furo[2,3-f], furo[2,3-g] and furo[3,2-g]quinoline
derivatives have been submitted to in vitro cytotoxic tests towards L 1210, MDA
MB 231 and PC3 cell lines. Among them, the furoquinone structures exhibited the
most interesting IC50 values.
PMID- 10192110
TI - Synthesis and biochemical screening of some new quinolino[3,2-c]oxazines.
PMID- 10192112
TI - Some azolylthioacetamides and their analgesic and antiinflammatory activities.
PMID- 10192111
TI - Synthesis and antimicrobial activity of flavone-6-carboxaldehyde oxime ether
derivatives.
PMID- 10192113
TI - Syntheses and antitumor activity of 4-[N'-[N-(2-chloroethyl)-N
nitrosocarbamoyl]hydrazono]-2,2,6,6- tetramethylpiperidine-1-oxyl.
PMID- 10192114
TI - Antimicrobial activity of some Nepalese medicinal plants.
PMID- 10192115
TI - Different kinetics of hydroquinone depletion in various medicinal plant tissue
cultures producing arbutin.
PMID- 10192116
TI - Daily changes in oxygen saturation and pulse rate associated with particulate air
pollution and barometric pressure.
AB - Epidemiologic studies have linked fine particulate air pollution with increases
in morbidity and mortality rates from cardiopulmonary complications. Although the
underlying biologic mechanisms responsible for this increase remain largely
unknown, potential pathways include transient declines in blood oxygenation and
changes in pulse rate following exposures to particulate air pollution episodes.
This study evaluated potential associations between daily measures of respirable
particulate matter (PM) with pulse rate and oxygen saturation of the blood. Pulse
rate and oxygen saturation (Spo2) using pulse oximetry were measured daily in 90
elderly subjects living near air pollution monitors during the winter of 1995-96
in Utah Valley. We also evaluated potential associations of oxygen saturation and
pulse rate with barometric pressure. Small but statistically significant positive
associations between day-to-day changes in Spo2 and barometric pressure were
observed. Pulse rate was inversely associated with barometric pressure. Exposure
to particulate pollution was not significantly associated with Spo2 except in
male participants 80 years of age or older. Increased daily pulse rate, as well
as the odds of having a pulse rate 5 or 10 beats per minute (bpm) above normal
(normal is defined as the individual's mean pulse rate throughout the study
period), were significantly associated with exposure to particulate pollution on
the previous 1 to 5 days. The medical or biologic relevance of these increases in
pulse rate following exposure to particulate air pollution requires further
study.
PMID- 10192117
TI - [Treatment of osteoid osteoma using laser photocoagulation. Apropos of 28 cases].
AB - THE PURPOSE OF THE STUDY was to evaluate interstitial laser photocoagulation for
local destruction of osteoid osteoma, with computed tomographic (CT) guidance.
MATERIAL AND METHODS: 28 patients (age range from 5 to 48 years) with presumed
osteoid osteoma were treated with CT-guided interstitial laser photocoagulation
of the nidus. A high power semiconductor diode laser (805 nm) with a 400 microns
optical fiber was used. The fiber was introduced into the nidus through a 18
gauge needle. Around the fiber tip, well-defined coagulative necroses from 5 to 9
mm (energy delivery, 400-1000J) were obtained. RESULTS: 27 patients had complete
pain relief, which was effective within 24 hours in 18 patients. One patient had
pain recurrence after 6 weeks. The remaining nidus was treated secondarily with
complete relief. Treatment was unsuccessful in one patient, and surgical excision
was performed. All patients were followed up for more than 1 year, with no sign
of recurrence. The only notable complication was a mild reflex sympathetic
dystrophy of the wrist in one patient. Sclerosis of the nidus was observed 6-12
months after the procedure. CONCLUSION: Percutaneous interstitial laser
photocoagulation of osteoid osteoma seems to be a promising, simple, precise, and
minimally invasive alternative to traditional surgical and percutaneous
ablations.
PMID- 10192118
TI - [Simple puncture versus trocar puncture biopsy for the bacterial diagnostic
evaluation of osteoarticular infections. A prospective study of 54 cases].
AB - PURPOSE OF THE STUDY: We have performed a prospective study in 54 patients with
suspected osteoarticular deep infection. The purpose of the study was to compare
notch needle-biopsy versus simple punction in term of bacteriological efficiency.
MATERIAL AND METHODS: Among 54 patients (32 males, 22 females), 16 cases of deep
infections were proven. There was 29 hips, 17 knees, 6 ankles, 2 elbows and 1
shoulder. Each patient was investigated with simple punction and notch needle
biopsy. Diagnostic value of both methods were evaluated by comparison with
results of surgical prelevement which was the gold standard for evaluating both
tests. The study was made using usual diagnostic test criteria: sensitivity,
specificity, positive predictive value, negative predictive value and also
likelihood ratio method. RESULTS: Sensibility for the simple punction was 31.25
per cent and sensibility for notch needle-biopsy was 69 per cent. Specificity for
simple punction was 97 per cent but for notch needle-biopsy it was 100 per cent.
Positive predictive value was respectively 83.33 per cent for simple punction and
100 per cent for notch needle-biopsy. Negative predictive value was 0.71 per cent
for simple punction and 0.31 per cent for notch needle-biopsy. Likelihood ratios
for simple punction was 11.87 and likelihood ratios for notch needle-biopsy was
infinite. DISCUSSION: Sensibility for notch needle-biopsy of 69 per cent is two
time superior to sensibility of simple punction. Notch needle-biopsy had no false
positive. It is a completely specific test. Methodology was valuable because all
patients who had negative result of non invasive test had no preoperative
antibiotherapy, and underwent surgery for bacteriological diagnostic only.
CONCLUSION: Notch needle-biopsy is always superior to simple punction. This study
leads us to modify our practice. From now on we will never use again simple
punction but we will only perform notch needle-biopsy which diagnostical
efficiency is superior.
PMID- 10192119
TI - [Kinematics of the healthy and arthritic hip joint during walking. A study of 136
subjects].
AB - PURPOSE OF THE STUDY: The study aimed to analyze the spatiotemporal parameters
and 3-dimensional pelvic and hip kinematic components during gait in two groups:
patients with a primitive osteoarthritis of the hip and control normal subjects.
MATERIAL: The study included 51 patients, ranged from 42 to 81 years, and 86
normal subjects. METHOD: Gait analysis was performed using the optoelectronic
system VICON with 5 cameras in free-speed conditions. Functional grading of the
patients was assessed by Lequesne's score. Thickness of the hip cartilage was
measured on pelvis AP radiograph. A preliminary study was performed to measure
reliability of the data on 11 patients. RESULTS: At the initial stage of
osteoarthritis, speed, cadence, stride length and hip flexion-extension motion
appeared as very close to normal data. After this initial stage, there was a
statistical relationship between these parameters and arthritis functional
grading. Pelvis rotation around the vertical axis did not change according to
severity of functional grading. The mean value of this component of pelvis motion
was 10 degrees in the pathological group, whereas it was 8 degrees in the female
normal group, and 7 degrees in the male group. There were no significant
relationship between radiographical thickness of hip cartilage and functional
grading of patients or gait parameters. DISCUSSION: This study demonstrates that
spatiotemporal gait parameters and kinematic data appear as quantitative index
which could be used in future studies. It also shows that pelvic rotation is
greater in pathological group than in normal subjects, even in the extreme
beginning of the hip osteoarthritis. This particularity can be explained as a
very early consequence of the arthritis or, in the opposite, as risk factor.
PMID- 10192121
TI - [Methods of shifting body weight in patients with knee arthroses].
AB - INTRODUCTION: The aim of this work was to study movement control strategies in
patients with knee arthritis. These strategies were expected to be different from
healthy subjects because of deficiencies due to knee arthritis (i.e. pain,
altered proprioception). METHOD: A kinetic and kinematic analysis was performed
in a population of 10 patients with unilateral knee arthritis and in 11 age
matched control subjects, using an ELITE system and two AMTI force-plates. The
different phases of a side step were studied. RESULTS: The timing of the movement
was different in the two populations. The postural phase was longer and the
monopodal phase was shorter in knee arthritis patients when the affected leg was
the supporting one than when the sound leg was supporting. Total step duration
and landing-stabilization phase duration were longer in knee arthritis patients
than in healthy subjects. CONCLUSION: This movement analysis method enables to
determine and to quantify differences between knee arthritis patients and control
subjects. Clinical examination cannot identify these differences. Movement
analysis methods bring up additional information to usual clinical evaluation
scales and could be used for evaluation of the results of total knee
arthroplasty.
PMID- 10192120
TI - [Failure of the polyethylene cups directly implanted into bone. A study of 32
Freeman cups after 9 years of followup (6-12 years)].
AB - PURPOSE OF THE STUDY: A clinical and radiological assessment was performed on 32
Freeman polyethylene uncemented acetabular cups, at an average of 9 years follow
up. This study was dedicated to analyze polyethylene bone direct fixation.
MATERIAL: Between 1984 and 1988, 30 patients were operated for 32 total hip
prostheses. Mean age of the population at the time of surgery was 66 years. In
all cases the prosthesis was a cemented Muller femoral stem with a Freeman
uncemented cup. The acetabular component was made with polyethylene with three
pegs fitted with an offset hemispheric cup. METHOD: All patients were reviewed at
1, 3, 5 years and maximal follow-up. Their functional evaluation was performed
using Merle d'Aubigne's hip rating scale: pain score, motion score and walking
score. Radiological assessment was performed to identify acetabular cup
migration, bone lysis, and radio lucency. Revision for acetabular cup loosening
was compiled. RESULTS: Five patients died, 27 THA were evaluated at maximum
follow-up. Seven revisions were performed after the fifth years. Merle
d'Aubigne's score was 14 at the time of revision. X-rays evidenced more than 5 mm
migration of the cup, with massive bone lysis. Merle d'Aubigne's score was 16 for
the 20 remaining THA. Radiologically, 10 cups showed migration less than 3 mm,
five of which with lysis. Among the 10 cups without migration, 5 showed sclerosis
near the acetabulum. The study evidenced that cases of migration exceeding 5 mm
induced a revision during the next 3 years. DISCUSSION: Our study confirms
failure of bone polyethylene direct fixation, with 25 per cent of revision after
a five years period. This seems to be the result of micro movement, wear and bone
lysis. A five years follow up is not sufficient to evaluate a component, since
all revisions were performed after five years. For many authors, radiological
evaluation of acetabular component migration is an important criterion for
uncemented prosthesis. The EBRA computerized method is an accurate method for
determining early migration, and can be used for pro and retrospective studies.
CONCLUSION: Our study confirms a high rate of failures of the Freeman uncemented
cup at an average of nine-year period, as previously reported in literature.
PMID- 10192122
TI - [The results after 10-16 years of the treatment of chronic anterior laxity of the
knee using reconstruction of the anterior cruciate ligament with a patellar
tendon graft combined with an external extra-articular reconstruction].
AB - PURPOSE OF THE STUDY: The aim of this prospective study was to evaluate the
objective postoperative laxity and functional results with a minimum follow-up of
10 years (mean 11.7 +/- 2 years) in chronic anterior knee instability treated by
ACL reconstruction associated to a lateral extra-articular plasty. MATERIAL AND
METHODS: 138 patients of a mean age of 27.8 +/- 8.5 years had been operated.
Delay between injury and operation was 4 +/- 4.8 years. The surgical "Mac
Injones" procedure used a free autologous patellar tendon graft with a bone-to
bone fixation, supplemented by a lateral extra-articular plasty using a strip of
quadriceps tendon as a direct prolongation of the graft of the patellar tendon
and patella itself. A rehabilitation program aimed to an early recovery of a
complete range of motion. Anterior laxity had been measured before and after
operation using two instrumented methods, KT-1000 and stress-radiography (at 20
degrees of flexion with a 9 kg load applied at the distal part of the thigh) with
measurements of the displacement in medial and lateral compartments. Tunnel
positioning was appreciated radiologically. Function was evaluated using the
International Knee Documentation Committee score (I.K.D.C.). RESULTS: Elongation
of the reconstructed ligament occurred mainly during the first 6 month, but was
independent from early full range of motion recovery. Laxity was stabilized after
one year. The final laxity gain of the medial compartment was 62 per cent and for
the lateral compartment 77 per cent. The pivot shift test was negative in 66 per
cent, grade 2 in 4 per cent, grade 1 in 30 per cent. Functional results were
excellent and good (A and B) in 60.4 per cent and 76.7 per cent returned to
sports activity. 12 reconstructed ligaments reruptured. Arthritis was the cause
of poor results in other cases (13.8 per cent). DISCUSSION: Lateral extra
articular plasty is unable to better control translation of the medial
compartment than isolated anterior cruciate ligament reconstruction, but laxity
of the lateral compartment was minimized and the pivot shift test also. Incorrect
position of the anterior cruciate ligament was correlated with poor results.
CONCLUSION: This documented study on laxity of the two compartments confirms the
interest of each type of reconstruction, in particular extra-articular plasty
when made with quadriceps tendon and so doing, preserving the iliotibial-band for
the control of varus stability.
PMID- 10192123
TI - [Reproducibility of the radiographic analysis of dysplasia of the femoral
trochlea. Intra- and interobserver analysis of 68 knees].
AB - PURPOSE OF THE STUDY: The relation between patello-femoral instability and
trochlear dysplasia was identified by Dejour. Trochlear dysplasia, diagnosed on
knee lateral Xray when the trochlear groove crosses both femoral condyles (the so
called "crossing sign"), must be corrected to improve patello-femoral stability.
However surgery should be related to the severity and the shape of trochlear
dysplasia, underlining the importance of a reproducible classification. The aim
of this study was to establish intra and inter-observer reliability of Dejour's
radiographic criteria. MATERIAL: 68 preoperative exact knee profile radiographs
were harvested from clinical records of 64 patients who underwent trochleoplasty
because of patello-femoral instability and trochlear dysplasia. On these 68
views, the crossing sign was identified by the senior surgeon (F.G.) who
performed or supervised surgery. METHOD: The 68 radiographs were examined
independently by 7 observers (2 juniors, 5 seniors) in order to assess
interobserver agreement. Two juniors repeated the observation to test
intraobserver agreement. Reproducibility for categorical data (7 shapes of
trochlea according to Dejour (3 for dysplasia)) was evaluated by Kappa
statistics, and for numerical data (depth and anterior projection of the
trochlear groove with respect to anterior femoral cortex) we used the interclass
correlation analysis. RESULTS: Two out of the 7 observers rated all the 68
trochleas as dysplastics. The 5 others rated as normal 1 to 6 trochleas out of
the 68. None of the 68 trochleas were recognized with the same shape by the 7
examiners. At best, 6 observers agreed on the same shape and for only 12
trochleas. Disagreement was mostly related to mistakes between type I and type II
of dysplasia. For trochlear morphology interobserver agreement was slight (Kappa
= 0.17) and intraobserver agreement was fair (Kappa = 0.3). The mean prominence
of the trochlea was 3 +/- 2.1 mm [-6 to 10], and the mean trochlea depth was 1 +/
1.9 mm [0 to 11]. These measurements were more reliable since the interclass
correlation coefficients were respectively 0.62 and 0.38. The level of experience
of the observers had no influence for categorical or numerical data. DISCUSSION:
Our results indicated a low interobserver agreement for trochlear shape
identification according to Dejour. The most reliable criteria was measurement of
the trochlear prominence which was mostly pathological in our series. The
"crossing sign" was reliable to diagnose dysplasia since the probability to rate
as normal a true dysplastic trochlea was only 3.1 per cent. However, once the
dysplasia diagnosed, this classification gave inconsistent results to select the
trochlear shape, particularly for type II. To improve reproducibility we propose
to diagnose a type II only when 5 millimeters separate the crossings between the
medial and lateral condyles. CONCLUSION: We recommend to use anterior projection
of the trochlear groove to rate trochlear dysplasia and to determine the adequate
type of trochleoplasty: elevating of the lateral facet if non prominent or
deepening of the groove when prominent.
PMID- 10192125
TI - [Local digital anesthesia using lidocaine with or without bicarbonate. A
comparative randomized study].
AB - PURPOSE OF THE STUDY: Local anesthesia with lidocaine is widely used in surgery
of the extremities, particularly for fingers. Injection causes pain. In order to
minimize this discomfort, addition of bicarbonate has been used by many authors.
Results were however contradictory in relation with the difference of approaches.
Our study is based on a randomized comparative series with and without lidocaine
alcalinization. MATERIAL AND METHODS: Sixty patients presenting multidigital
trauma concerning at least two fingers. For each patient, one finger was
anesthetized by lidocaine 2 per cent alone and one by lidocaine 2 per cent plus
bicarbonate 8.4 per cent respectively in proportion of 4/5 and 1/5. We compared
the intensity of pain during injection by a scale ranging from 0 to 10. RESULTS:
Significant difference was found between both groups (p < 0.001), alcalinization
appearing to decrease discomfort during injection. DISCUSSION: Mechanism of pain
decrease by alcalinization is unclear. It appears that intracellular passage of
non ionic form of lidocaine is facilitated by alcalinization. This allows the
decrease of latence of lidocaine and relieve pain more rapidly by pain receptors
blockade. CONCLUSION: Diminution of pain during anesthetic injection has major
advantage in out-patient surgery of extremities, in ligamentar testing of digital
articulations and in steroid injection.
PMID- 10192124
TI - [Is calcaneal osteotomy justified in Haglund's disease?].
AB - PURPOSE OF THE STUDY: The authors report their experience of Zadek's wedge
osteotomy in the treatment of posterior talalgia in adults and evaluate the
various radiographical measurements for calcaneus deformity measurement....
MATERIAL: This procedure was performed in 27 patients with a total of 36 calcanea
treated between 1985 and 1996. The sex ratio was 20 women for 7 men with an
average age of 27 years. Prior to this osteotomy nine feet were operated by
resection of the postero-superior tuberosity with recurrence of pain and
disability, and two patients presented an inflammatory arthritis. METHOD: For the
surgical procedure, the patient was placed in lateral position. Skin incision was
five to six centimeters long, curvilinear along the lateral side of the tendo
achillis. Two dorsal pins were inserted, creating a triangle so that the apex
pointed plantarly and the base dorsally. The sagittal saw was then used to create
a wedge osteotomy with a dorsal base of seven to ten millimeters. A screw was
then driven across the osteotomy site for ultimate fixation. RESULTS: Eighty per
cent (29 osteotomies) of patients had been examined clinically and radiologically
with a mean follow-up of 29 months. Considering pain, daily activity and
discomfort with footwear, results were excellent in 12 cases, good in 10, fair in
5 and poor in two cases. No radiological criteria used for the diagnosis of
Haglund's disease were absolutely reliable. The "total angle" of Ruch, the "c.l
angle" of Chauveaux and the "parallel pitch lines" of Heneghan reflect the amount
of deformation most accurately, but especially, the calcaneal inclination angle
was always increased (16 cases between 18 degrees and 30 degrees, 6 cases > 30
degrees). All patients had a weight-bearing calcaneal talus, either alone or in
the context of posterior pes cavus. CONCLUSION: This study confirms the
responsibility of rearfoot morphostatic disorders in posterior talalgia and the
goods results obtained by Zadek osteotomy.
PMID- 10192126
TI - [Bisphosphonates and bone remodeling: effectiveness in Paget's disease, fibrous
dysplasia and osteoporosis].
AB - Paget's disease of bone, bone fibrous dysplasia and osteoporosis are
characterized by abnormal bone remodeling, and frequently imply intervention of
orthopedists. Recent significant medical therapeutics improvements have been
obtained with the use of bisphosphonates. Theses drugs decrease bone remodeling.
In Paget's disease, bisphosphonates relieve bone pain, allow lytic areas
refilling and decrease complications risk with normal bone formation. In fibrous
dysplasia, bone pain is alleviated, osteolytic areas are refilled and cortices
are widened. In postmenopausal osteoporosis, bisphosphonates increase bone
mineral density, and reduce very significantly the subsequent risk of vertebral,
femoral and lower forearm fractures. Bisphosphonates are a breakthrough in
Paget's disease of bone, fibrous dysplasia of bone and osteoporosis.
PMID- 10192127
TI - [Patellar entrapment due to a force-impaction fracture of the lateral condyle.
Apropos of a case].
AB - Dash board injuries lead to well known osseous or ligamentous injuries. The
authors report a case of femoral condyle impaction fracture with patellar
entrapment. The deepening trochleoplasty experienced by H. Dejour in patellar
instabilities was used for lateral condyle resurfacing. The final result after
one year was excellent.
PMID- 10192128
TI - [A new location of osteochondritis: the os trapezium. Apropos of a case].
AB - The authors report a case of osteochondritis dissecans of the trapezium in a 10
year old boy. The main symptom was pain. X-Rays showed osteosclerosis and
diminished volume of the trapezium. Magnetic resonance imaging confirmed the
diagnosis. At six months, the patient was almost asymptomatic and at one year, X
Rays and the MRI were judged normal. This localisation has never been reported
before. The treatment was conservative. Remission was complete.
PMID- 10192129
TI - ["10-year followup of Zweymuller's total prosthesis in primary non-cemented hip
arthroplasty"].
PMID- 10192130
TI - ["Acute compartment syndrome of the post-traumatic leg"].
PMID- 10192131
TI - Effects of cadmium on lipid peroxides and superoxide dismutase in hepatic, renal
and testicular tissue of rats.
AB - Daily i.p. administration of 0.5 mg cadmium (Cd)/kg body weight to rats for 3 mo
enhanced lipid peroxidation and inhibited superoxide dismutase (SOD) activity in
liver, kidney and testes. Accumulation of Cd and SOD inhibition was maximum in
liver followed by kidney and testes, indicating a direct effect of Cd on SOD
activity. This suggests a role of free radicals in causing cellular damage with
long-term exposure to cadmium.
PMID- 10192132
TI - Evaluation of hepatic changes and weight gains in sheep grazing Kochia scoparia.
AB - Sixteen Western Whiteface ewes were divided into 2 groups to determine the
effects of plant maturity on liver function and weight gains. They were allowed
to graze a greater than 95% pure stand of Kochia scoparia for 72 or 55 d. Four
additional sheep (controls) were placed on weedy Bermuda grass pasture with the
same water supply as the kochia-fed sheep. Body weights were determined on June
5, 1996 and on removal from the kochia pasture. Blood samples were collected at
approximately 7-d intervals for serum chemistry profiles. Kochia scoparia plant
samples were also randomly collected at 5-6 w intervals, oven dried, identified
by date of collection and stored for later nutrient, oxalate, nitrate and sulfate
analysis. Liver biopsies were performed pre-, mid- and post-study to assess
morphologic changes. An almost exclusive diet (> 95%) of Kochia scoparia resulted
in minimal elevations in serum GGT, suggesting mild hepatocellular injury, but
was not associated with overt hepatic lesions or clinical disease. Other serum
chemistry measurements were within normal ranges. Unlike for other domestic
animal species, Kochia scoparia may be a useful grazing forage for sheep,
offering little risk of toxicosis.
PMID- 10192133
TI - Organochlorine pesticide and polychlorinated biphenyl residues in Canada geese
(Branta canadensis) from Chicago, Illinois.
AB - Breast muscle samples, with or without overlying adipose tissue and skin, were
obtained from Canada geese collected in northeastern illinois while undergoing
feather molt. Specimens were evaluated for contaminant concentrations to
determine if they would be acceptable as human food provided through government
subsidized programs. Samples were baked, allowing fat to drip free, and assayed
for persistent organochlorine pesticides and polychlorinated biphenyls. Residues
of heptachlor epoxide, dieldrin, DDE and PCBs (as Arochlor 1248) were detected.
The specimens contained relatively low concentrations of contaminants, such that
US Department of Agriculture residue limits for meat were exceeded in only 1
sample. Baking of breast muscle without the overlying skin and adipose tissue
resulted in reductions in concentrations of detectable compounds. Fewer samples
baked with the skin attached had detectable concentrations of heptachlor epoxide,
dieldrin and PCB then samples cooked without skin; however, the converse was true
for DDE. Periodic monitoring for environmental contaminants such as PCBs,
exclusion of geese from localities where samples have contaminants such as PCBs,
exclusion of geese from localities where samples have contaminants at
concentrations that exceed recommended dietary limits, the use of processing
and/or cooking methods which remove large amounts of lipid, and advisories that
provide information on known health risks are recommended if wild resident Canada
geese from the Chicago area are provided as food for underprivileged humans.
PMID- 10192134
TI - Safety of 25-hydroxyvitamin D3 as a source of vitamin D3 in turkey rations.
AB - A target animal safety study investigated the effects of providing 25
hydroxyvitamin D3 (25-OH-D3) as a replacement for vitamin D3 in pelleted turkey
feeds. Five groups of turkeys were fed diets containing vitamin D3 at 68.9
micrograms/kg feed (control) or 25-OH-D3 at concentrations of 49.5 (0.5x), 99
(1x), 495 (5x) or 990 (10x) micrograms 25-OH-D3/kg feed. The effects of 25-OH-D3
or vitamin D3 on performance, health, hematology, gross pathology and tissue
concentrations of 25-OH-D3 in female and male turkeys were compared at 112 days
of feeding. There was no significant difference from control in pen body weight
in any of the groups. When feed conversion was calculated without taking into
account body weights of birds that died during the study, there was no
significant difference from control in any of the groups. When feed conversion
was corrected for mortality, the only significant effect was that females at the
5x level (495 micrograms 25-OH-D3/kg feed) had improved feed conversion.
Significantly increased mortality occurred during the study in the 10x (990
micrograms 25-OH-D3/kg feed) male group only. No histomorphologic tissue
alterations attributable to dietary administration of 25-OH-D3 were observed in
tissues examined at any dietary level of 25-OH-D3. 25-OH-D3 did not adversely
affect animal health at the proposed use level of 99 micrograms/kg feed when
replacing vitamin D3 in turkey rations. The proposed use level also provides at
least a 5-fold margin of safety.
PMID- 10192135
TI - Management of neuroleptic malignant syndrome with anticholinergic medication.
AB - Neuroleptic Malignant Syndrome (NMS) is a life-threatening adverse reaction
arising from the use of neuroleptic medications. While dopaminergic agonists,
dantrolrene and supportive care are traditionally utilized in the stabilization
and management of NMS, anticholinergic medication may also prove effective
therapy. Treatment with anticholinergic medication has been suggested in cases of
NMS associated with mild hyperthermia. We describe a case of 17-y-old female, who
was brought to the emergency department for a possible "acute dystonic reaction".
The patient received 50 mg diphenhydramine i.v., which resulted in improvement in
mental status. The patient was readmitted to the emergency department 1 d
following discharge with symptoms similar, but now considering the diagnosis of
NMS. Diphenhydramine 50 mg i.v. was again administered and resulted in
significant improvement.
PMID- 10192136
TI - Fatal ingestion of sodium hypochlorite bleach with associated hypernatremia and
hyperchloremic metabolic acidosis.
AB - Ingestion of sodium hypochlorite bleach is usually benign, leading most poison
centers to advocate conservative, home management. We report a rare, fatal case
of household bleach ingestion. A 66-y-old female ingested an unknown quantity of
regular CLOROX bleach (5.25% sodium hypochlorite, pH = 11.4). Upon discovery, she
was vomiting spontaneously, and had slurred speech and oral mucosal
discoloration. On hospital arrival the patient became unresponsive with shallow
respirations. Laboratory studies revealed hypernatremia (169 mEq Na/L),
hyperchloremia (143 mEq Cl/L), and metabolic acidosis (5 mmol total CO2/L).
Radiographic evaluation showed bilateral pneumothoraces and pneumoperitoneum. The
patient was intubated and ventilated, hypotension was treated with fluid
resuscitation, and metabolic acidosis corrected with sodium bicarbonate. Naloxone
and flumazenil were given without effect, and thoracostomy tubes were placed.
Rapid deterioration of vital signs and mental status ensued, with
cardiorespiratory arrest from which she was resuscitated. A second cardiac arrest
resulted in death. Autopsy revealed esophageal and gastric mucosal erosions,
perforation at the gastroesophageal junction, and extensive necrosis of adjacent
soft tissue. Stomach contents contained sodium hypochlorite, and pleural and
peritoneal fluid had the aroma of bleach. Postmortem vitreous humor Na was 187
mEq/L and Cl was 169 mEq/L. Toxicologic analysis revealed meprobamate metabolites
in the urine, and lidocaine in the blood. The literature regarding fatal bleach
ingestion is reviewed.
PMID- 10192137
TI - Chlorpyrifos: a ten-year US poison center exposure experience.
AB - We performed a retrospective review of data based on poison center exposure
inquiries related to chlorpyrifos (CP) and the corresponding poison center
determined medical outcomes reported to the Toxic Exposure Surveillance System
(TESS) of the American Association of Poison Control Centers. Ten y (1985-1994)
of TESS data were obtained. Medical outcomes representing all inquiries,
accidental/unintentional inquiries, and intentional/suicidal inquiries were
tabulated. Published TESS data was also tabulated to allow comparison of CP
exposure inquiries to all non-pharmaceutical and insecticides/pesticides exposure
inquiries for like time periods. Frequency of antidote use, product sales data,
CP-related fatality reports, and pertinent issues related to telephone derived
surveillance data were also reviewed; 36, 183 CP exposure inquiries were
identified. Of all CP exposure inquiries, 27, 473 (75.9%) were assessed as having
no significant health consequences; 4,511 (12.5%) outcomes were judged unrelated
and 2,980 (8.2%) were unable to be followed. Reported significant medical
outcomes for the remaining exposure inquiries were moderate 1,092 (3.0%), major
119 (0.3%) and death 8 (0.02%). Considering only calls with outcomes judged
causally related to CP, where a given level of effect could reasonably be
determined, 95.8% (27,473/28,692) of these calls resulted in no significant
health effects. Use of antidotes specific to organophosphates were infrequent
[atropine, 1.0% (385) and 2-PAM, 0.5% (177) of all cases respectively]. Despite
the number of reported CP exposure inquiries, relatively few resulted in outcomes
of consequence. TESS data suggested that the majority of patients undergoing
medical evaluation and/or treatment after a suspected CP exposure do not require
specific antidotes. TESS data serves as a useful first step in evaluating product
safety. Assessment of product toxicity requires additional investigation of
reported adverse effects and circumstances related to the incident.
PMID- 10192138
TI - Urticaria due to airborne permethrin exposure.
AB - Although naturally derived pyrethrins are well recognized sensitizers, there is
currently some degree of controversy regarding the sensitizing potential of
synthetic pyrethroids. The literature is briefly reviewed, and an outbreak of
several cases of urticaria occurring in children from 1 household and associated
with airborne exposure to permethrin is reported.
PMID- 10192139
TI - Ethanol analysis following consumption of "alcohol-free" beer.
AB - Breath alcohol devices are routinely employed by emergency department personnel
to reflect blood ethanol levels. No data have been published using these devices
following the ingestion of "alcohol-free" beer that are required to contain <
0.5% alcohol. We performed a prospective, randomized, unblinded study on 8
healthy male volunteers that abstained from alcohol for 48 h and fasted for 10 h.
Each subject ingested a 6-pack of alcohol-free beer over 1 h; breath alcohol
determinations were made at 30, 60 and 120 min. Elevated breath alcohol levels
were obtained at 30 and 60 min and decreased in all but 1 subject by 120 min. The
elevated breath alcohol levels at 30 and 60 min may represent the previously
reported "mouthwash" effect.
PMID- 10192140
TI - Hepatotoxicity associated with pyrrolizidine alkaloid (Crotalaria spp) ingestion
in a horse on Easter Island.
AB - Since 1984, a significant number of privately owned and feral horses on Easter
Island have died of a syndrome consisting of progressive anorexia, weight loss,
obtundation, and other central nervous system abnormalities. A single horse
experiencing clinical signs of the reported syndrome was identified, examined and
necropsied. Clinical signs included inappetence, emaciation, ataxia and icterus.
Gross necropsy findings included hepatic enlargement and mottling, ascites and
gastric impaction. Histopathological lesions included hepatic hemorrhage and
necrosis, periportal megalocytosis, portal fibrosis, bile duct hyperplasia and
multinucleate hepatocytes. Crotalaria grahamiana and C pallida, were identified
in the pasture of the presenting horse, and found to be widespread on the island.
Alkaloid fingerprinting identified grahamine, monocrotalin, and a grahamine
analog in C grahamiana. A retrorsine analog and a senecionine analog were
identified in C pallida. The highly characteristic lesions and the identification
of pyrrolizidine alkaloids in the 2 plants strongly suggest that ingestion of 1
or both of the Crotalaria species led to chronic liver damage and hepatic
encephalopathy in the presenting horse. Widespread distribution of C grahamiana
on the island and reported temporal and seasonal trends in incidence among horses
and cattle suggest that C grahamiana may be responsible for extensive morbidity
and mortality among horses and cattle on Easter Island.
PMID- 10192141
TI - The pattern of poisoning in Costa Rica during 1997.
AB - The Poison Control Center of Costa Rica has provided service since 1969. It
attends calls from health professionals and the community in general regarding
poisoning situations. The purpose of this study is to describe the pattern of
poisonings reported to this Center during 1997. Drugs were the principal agents
involved (49.2%) followed by pesticides and cleaning agents. Children under the
age of 5 accounted for 39.2% of cases. Accidental circumstances were the
predominant cause of poisoning in children. Among adults, suicide attempts
prevailed. The male of female ratio was 1.05. Oral ingestions were the most
frequent route of exposure (76.8%). It takes education and conscious efforts from
everyone to help reduce poisoning cases.
PMID- 10192142
TI - A natural sobriety enzyme: a party pill or snake oil?
AB - Promoters of a recently marketed "natural dietary supplement" called ALCOZYME
claimed the product could rapidly and dramatically lower the blood ethanol
concentration by metabolizing ethanol from the blood. We undertook a
demonstration of the product in accordance with labeled instructions to replicate
the results described by the manufacturer. We also tested ALCOZYME invitro in a
solution of known ethanol concentration to determine whether the product directly
degrades ethanol. In human volunteers, ALCOZYME showed no tendency toward
mitigating blood ethanol concentrations and had no effect on the clinical signs
of alcohol intoxication. ALCOZYME did not metabolize ethanol invitro.
PMID- 10192143
TI - [Medical observations on definition of death].
PMID- 10192144
TI - [Nothing new in treatment of acute renal failure?].
PMID- 10192145
TI - Anticoagulation with prostaglandins during extracorporeal circulation.
AB - This paper reviews pathophysiological processes occurring after contact of blood
with artificial surfaces and the predominant role of platelets in the genesis of
extracorporeal thrombosis. Bleeding complications are common during conventional
heparin anticoagulation, and both clinical and experimental evidence suggests
that the efficacy of heparin as an anticoagulant is compromised by its relative
ineffectiveness towards platelets. Consequently, drugs that inhibit interaction
between platelets and artificial membranes have been introduced as an alternative
anticoagulant strategy. This paper reviews studies on the use of short-acting
antiplatelet prostaglandins such as prostacyclin and prostaglandin E1 alone or in
combination with heparin during various forms of extracorporeal circulation such
as cardiopulmonary bypass, haemodialysis, continuous haemofiltration, membrane
oxygenation, ventricular assist devices, and haemoperfusion. Temporary paralysis
of platelet function with antiplatelet prostaglandins has been effective in
controlling platelet-surface interaction and reducing bleeding complications and
morbidity during and after extracorporeal circulation. By inhibiting the
formation of fibrin, leukocyte and platelet-based microaggregates and
cytoprotective actions, prostaglandins have been shown to prevent renal,
neurologic, and pulmonary dysfunction after extracorporeal circulation.
Prostaglandins were most effective in increasing the biocompatibility of
extracorporeal systems when they were administered as a supplement to but not as
a substitute for heparin. The use of prostaglandins alone should be reserved for
patients who are resistant to heparin or heparin-induced thrombocytopenia.
PMID- 10192147
TI - [Recollections of ventilated patients after a stay in the intensive care unit].
AB - A review of the literature reveals only scarce data and observations concerning
the recollections of patients treated in a intensive care unit, although
intraoperative awareness under general anaesthesia has been extensively reported.
In the present study we investigated the recollections of patients who had
undergone artificial ventilation in intensive care units. METHODS: Fifty patients
who had undergone mechanical ventilation in intensive care units at the
University Hospital of Vienna were retrospectively interviewed in regard of their
experience during the treatment. A score was used to quantify discomfort.
RESULTS: All patients remembered having been treated at the intensive care unit.
The most unpleasant experience was tracheal suctioning which was remembered by
60%. The next most unpleasant experience was extubation; 52% remembered this
intervention. Eighty-four per cent of patients remembered the medical staff, 90%
of them had confidence in them, 86% remembered the nursing staff and 91% had
confidence in them. CONCLUSION: In spite of unpleasant memories of intensive care
treatment, of which tracheal suctioning was perceived as most unpleasant, the
majority of patients expressed a positive evaluation of their treatment at the
intensive care unit.
PMID- 10192146
TI - Concomitant treatment with urodilatin (ularitide) does not improve renal function
in patients with acute renal failure after major abdominal surgery--a randomized
controlled trial.
AB - Acute renal failure after major abdominal surgery is a severe complication in
critically ill patients in intensive care units (ICU). The aim of the study was
to investigate the effect of urodilatin on the peak value and course of serum
creatinine in patients with acute renal insufficiency after major abdominal
surgery and the necessity of apparatus-based renal replacement treatment.
Furthermore, the incidence and nature of adverse events under urodilatin was
documented. In a prospective randomized double-blind placebo-controlled study, 12
critically ill patients after major abdominal surgery with acute renal failure in
an intensive care unit (ICU) received 20 ng/kg b.w./min urodilatin (ularitide,
INN) or placebo in addition to the standard diuretic therapy or low-dose dopamine
(2.5 micrograms/kg b.w./min) and furosemide (1000 mg/24 hr) for a minimum of 96
hours. All patients received mechanical ventilation. Both groups had similar
serum creatinine values on the day before the onset of urodilatin/placebo
infusion (2.80 +/- 0.24 mg/dl, 2.93 +/- 0.48 mg/dl). Peak serum creatinine was
lower in the urodilatin group (4.65 +/- 0.57 mg/dl) compared to vehicle treatment
(5.78 +/- 1.58 mg/dl), although the difference did not reach statistical
significance (P = 0.148). The total number of hemodialyses due to oligo-/anuria
and/or hyperkalemia was the same in both groups during the study. In 4 patients
of the placebo group, diuresis was reduced to anuria, whereas only 1 of the
patients treated with urodilatin became anuric. No hemodynamic side effects or
adverse events due to urodilatin were observed. This clinical study under double
blind conditions revealed that the addition of urodilatin to the standard
diuretic therapy of low-dose dopamine and furosemide failed to improve renal
function in patients with established acute renal failure and that urodilatin did
not eliminate the need for apparatus-based renal replacement treatment.
PMID- 10192148
TI - Detection of Chlamydia pneumoniae DNA in atheromatous tissues by polymerase chain
reaction.
AB - Chlamydia pneumoniae is an important human respiratory pathogen. Recently,
seroepidemiological data and the demonstration of chlamydial DNA or antigen
within parts of atherosclerotic lesions have suggested a causal association
between chlamydial infections and atherosclerosis. As the results obtained by
different groups show considerable variations, we provide further data based on a
highly specific and sensitive nested PCR method. Positivity was confirmed by
nonradioactive hybridization with a specific probe, and sensitivity was
determined by titration experiments. C. pneumoniae DNA was detected in 8/29 (28%)
of carotid artery samples and 3/14 (21%) of aortic aneurysms.
PMID- 10192149
TI - Fulminant lethal tuberculous pneumonia (Sepsis tuberculosis gravissima) with ARDS
in a non-immunocompromised western European middle-aged man.
AB - We report the case of a 42 years old, non-immunocompromised native Austrian
living in Vienna. He presented at home with severe dyspnea and had to be
intubated immediately. Shortly after hospital admission, he developed severe
adult respiratory distress syndrome (ARDS) and septic shock with massive, bilobar
patchy to confluent infiltrations and a need for norepinephrine. A CT-scan
revealed severe loss of functional lung tissue with areas of consolidation and
multiple communicating cystic spaces. Air leaking into the mediastinum through
fistulas produced pneumomediastinum, pneumoperitoneum, and a massive soft tissue
emphysema. Bronchoalveolar lavage performed within the first 24 hours of
admission revealed + of acid-fast bacilli. Even though appropriate
tuberculostatic medication was started immediately, the patient succumbed the
next day to ARDS due to massive tuberculous pneumonia and miliary disease (Sepsis
tuberculosis gravissima).
PMID- 10192151
TI - [Unstable coronary syndrome. Therapeutic possibilities of the use of low
molecular heparins].
PMID- 10192150
TI - [On the topic of do not resuscitate (DNR) orders on intensive care units: an
evaluation of the present status on intensive care units of the Innsbruck
University clinics].
AB - INTRODUCTION: Intensive care physicians are frequently called upon to decide
whether intensive care treatment is justified. Critically ill patients with a
poor prognosis receive "Do Not Resuscitate (DNR) Orders", which entitles the
physician in charge to withhold cardiopulmonary resuscitation in case of cardiac
arrest. Guidelines concerning the implementation of DNR orders do not exist for
Austrian intensive care units. The aim of this study was to evaluate the
different practices of issuing a DNR order in the departments of intensive care
medicine at the University Hospital of Innsbruck. METHODS: Forty-nine physicians
working in intensive care units were interviewed about the different procedures
in the management of a DNR order. Furthermore, the various answers of senior
physicians and assistant physicians were evaluated. RESULTS: Thirty-nine per cent
of the interviewed physicians reported that DNR orders were always issued in
writing. According to the answers of 63% of intensive care physicians, the
decision to issue a DNR order is usually made by senior physicians. Twenty-nine
per cent mentioned that nurses are never included in the decision making process
and 6%, that the family is not included in the decision making process. According
to 29%, the family is regularly informed about a written DNR order. Twenty per
cent of the interviewed physicians reported that the quality of the
administration of a written DNR order is very good, 6% that the quality is poor.
CONCLUSION: We believe that the unsatisfactory situation in regard of DNR orders
is not due to inactivity on the part of physicians, but is more likely a result
of the inconclusive and, in part, contradictory legal situation. The physician is
compelled to take a major decision within a poorly defined legal situation.
PMID- 10192152
TI - [Coronary heart disease. Nitrate therapy without tolerance].
PMID- 10192153
TI - The International Society of Dermatology in the next millennium: from the banks
of the Mississippi to the banks of the Nile.
PMID- 10192154
TI - The value of sunscreens.
PMID- 10192155
TI - Quantitative estimation and recommendations for supplementation of protein lost
through scaling in exfoliative dermatitis.
AB - BACKGROUND: Exfoliative dermatitis (ED) can result in protein loss due to scaling
causing a negative nitrogen balance. Freedberg and Baden (J Invest Dermatol 1962;
38: 277-284) estimated the amount of scale lost in ED by collecting it in an
occlusive suit. Subsequently, the nitrogen content was determined by the Kjeldahl
method. The exact amount of protein supplementation in ED, dependent on scale
loss, is not well established. As occlusion and hyperthermia caused by the suit
can inhibit scaling, the objectives of the present study were to design an
alternative method to measure the amount of scale lost, to estimate the protein
content of the scale, and to propose suitable recommendations for protein
supplementation. METHODS: In 40 patients with ED, the total protein content lost
through scaling per day (P) was determined by the following equation: P =
TxIxYxX/25x10(4) g, where T is the total body surface area in square meters, I is
the percentage area involved in scaling, estimated using computer-aided design
(CAD graph), Y is the amount of scale lost per unit area (0.0025 m2) in
milligrams, and X is the quantity of protein present in 1 g of scale in
milligrams estimated by a spectrophotometer. RESULTS: It was observed that
patients with ED secondary to drug reactions, eczema, and psoriasis lost 7.2,
9.6, and 22.6 g of scale with a protein content of 4.2, 5.6, and 12.8 g
respectively. The difference in the amount of protein lost in ED secondary to
drug reactions and eczema was not statistically significant; however, the protein
lost in psoriasis was significant (p < 0.01 to p < 0.05). CONCLUSIONS: ED may
increase the daily protein loss by approximately 25-30% in psoriasis and 10-15%
in other causes. Standard treatment for ED and protein supplementation based on
our recommendations can minimize the adverse effects of a negative nitrogen
balance.
PMID- 10192156
TI - Relevance of complement fixing antinuclear antibodies.
AB - BACKGROUND: Connective tissue diseases (CTDs) are a heterogeneous group of
disorders defined by the association of a variety of clinical manifestations with
immunologic and other laboratory findings. Overlap of syndromes and aberrant
findings appear rather frequently. METHODS: Sera of eight antinuclear antibody
(ANA) negative, cases of subacute cutaneous lupus erythematosus (SCLE) with
antibodies to Ro (SS-A) and a ninth case with clinical and laboratory signs of
Sjogren's syndrome and systemic lupus erythematosus (SLE) were tested for
complement (C') fixing antinuclear antibodies (C-ANAs). The ninth case was
examined in depth by direct immunofluorescence (DIF) and a two-step "C + DIF"
test of biopsies for C' fixation to in vivo bound ANAs, as well as serum tests
for C-ANA, ANA, and SCLE markers. RESULTS: Sera of five of the eight ANA
negative, Ro(SS-A) positive SCLE cases had C-ANAs. The ninth case, a 50-year-old
woman with clinical and laboratory signs of Sjogren's syndrome and SLE, gave a
strong positive C + DIF reaction in the skin biopsy for in vivo bound ANAs that
fix C', but negative ANAs and C-ANAs in routine serum tests; they revealed
antimitochondrial antibodies. Serum tests on normal skin, however, revealed weak
ANA and strong C-ANA reactions with in vitro fixed C'. CONCLUSIONS: ANA negative
cases of SCLE or Sjogren's syndrome may have C-ANAs. A case with Sjogren's
syndrome and signs of SLE had both in vivo and in vitro C' fixing ANAs. C-ANA
tests can aid in the identification of such cases.
PMID- 10192157
TI - Melanoma in Kauai, Hawaii, 1981-1990: the significance of in situ melanoma and
the incidence trend.
AB - BACKGROUND: The incidence of melanoma has often been portrayed as reaching
'epidemic' proportions. The reality of such an epidemic is, however, not clearly
established due to the methods of data collection and interpretation. The
population-based incidence data and incidence trend of melanoma from the Island
of Kauai, Hawaii provide an illustration of this 'epidemic'. METHODS: We used
medical records housed at the dermatology clinic and pathology laboratory in
Kauai to: identify residents of Kauai who had their first melanoma during the
years 1981-1990; and to measure the 10-year population-based incidence of
melanoma. RESULTS: In Caucasians: A total of 53 Caucasian residents (29 men and
24 women), were identified with an initial episode of melanoma (MM) during the 10
year period. The average annual standardized incidence rate per 100,000 Kauai
Caucasian residents was 36. Whereas the incidence of in-situ MM increased during
the 10-year period, the incidence of invasive MM did not. The average patient age
was 55 years. The trunk and the limbs were the most common anatomic sites of MM.
In men, one third of MM occur on the back. In women, one third develop on the
leg/thigh. Three patients (6%) had metastasis and eventually died of MM. Thirteen
patients (25%) had other skin cancers such as basal cell carcinoma and squamous
cell carcinoma at some time. In Filipinos, Japanese and Hawaiians: Three
Filipinos (all women), two Japanese (one man and one woman) and one Hawaiian
(man) had melanoma. The standardized incidence rates, to the U.S.A. Caucasian
population, were 3.1, 0.8 and 2.1 per 100,000 residents, respectively.
CONCLUSIONS: The melanoma incidence in Kauai is one of the highest rates
documented in the U.S.A. However, a decreased incidence of invasive melanoma
during the 10-year period was unexpected. The finding of nonmelanoma skin cancer
in these patients supports a common etiology among these skin cancers.
PMID- 10192158
TI - Squamous cell carcinoma and keratoacanthoma of the lower lip associated with
"Goza" and "Shisha" smoking.
AB - BACKGROUND: A positive correlation between lip and buccal cancers and pipe
smoking has been suggested. Various types of crude and manufactured tobacco
products are consumed by smoking, chewing, and snuff dipping habits. 'Shisha" and
'Goza' smoking are widely practiced in the Middle East. The 'hubble-bubble'
method and apparatus are used. These smoking habits are hazardous to health,
causing obstructive lung disease, and may be important predisposing factors for
the development of oral cancers. CASE REPORTS: Two cases of squamous cell
carcinoma and a case of keratoacanthoma localized to the lower lip are presented
in well-known 'Shisha' and 'Goza" smokers. CONCLUSIONS: "Shisha" and 'Goza'
smoking have adverse effects on general health and may predispose to oral cancer.
An extensive epidemiological study should be performed to determine whether this
type of smoking habit is associated with a statistically increased incidence of
squamous cell carcinoma and keratoacanthoma of the lips.
PMID- 10192159
TI - Atypical cutaneous lymphoproliferative disorder in patients with HIV infection.
AB - BACKGROUND: An inflammatory pruritic eruption which is characterized
histologically by CD8+, atypical lymphocytes has been described in human
immunodeficiency virus (HIV)-infected patients. This disorder has been described
as "pseudo-Sezary" or a "cutaneous T cell lymphoma (CTCL)-simulant", however, as
these patients do not resemble CTCL clinically, and the relationship between this
entity and CTCL is unclear, a more descriptive term is "atypical cutaneous
lymphoproliferative disorder" (ACLD). The purpose of this study is to categorize
the clinical, histologic, and immunophenotypic features of 16 HIV-infected
patients with this skin disorder seen at the New York Department of Veterans
Affairs Medical Center. METHODS: A retrospective chart review was conducted on 16
HIV-infected patients with a histologic diagnosis of an atypical cutaneous
lymphoproliferative infiltrate on skin biopsy. Skin biopsies were reviewed, and
histologic features noted. Immunophenotyping was performed on 14 out of 16
samples; electron microscopy was performed on samples from five patients.
Clinical manifestations, disease course, medication history, and response to
treatment were noted. RESULTS: The patients presented with a pruritic,
persistent, generalized, papular eruption. Pigment changes, including
hyperpigmentation and hypopigmentation were common. Histologically, lesional
biopsies were characterized by a superficial and deep polymorphous infiltrate
with atypical lymphocytes which were CD8+ predominant, Ki-1 negative, and
occasionally CD7 antigen depleted. Sezary-like cells were present in the
infiltrate in four out of five patients by electron microscopy. None of the
patients has systemic manifestations of lymphoma; however, one of the 16 patients
eventually developed frank CTCL. CONCLUSIONS: HIV-infected patients can present
with a pruritic, widespread disorder, often with pigment changes characterized by
an atypical cutaneous lymphocytic infiltrate. This clinicopathologic disorder is
a rare, reactive inflammatory condition which generally occurs in late stage HIV
infection and rarely progresses to frank lymphoma.
PMID- 10192160
TI - Cutaneous infections by papillomavirus, herpes zoster and Candida albicans as the
only manifestation of idiopathic CD4+ T lymphocytopenia.
AB - BACKGROUND: Selective depletion of CD4+ T lymphocytes is common in both primary
and secondary immunodeficiencies. Idiopathic CD4+ T lymphocytopenia (ICL) cases
are defined as a persistent CD4+ T lymphocyte count of less than 300x10(6)
cells/L and/or less than 20% of the total T-cell count. METHOD: A 40-year-old
woman, with a history of psoriasis and paracetamol allergy, presented with
persistent warts of the hands and condylomas of the ano-genitalia. Histological
and virological analysis was carried out on genital and cutaneous lesions and
peripheral blood. RESULTS: Serology for HIV-1, HIV-2, Epstein-Barr virus and
parvovirus B19 were negative. There was lymphopenia of 10% CD4+ cells, with
normal numbers of total leukocytes; there were no other-abnormal immunological
findings. DNA analysis of cutaneous lesions revealed HPV-49 and HPV-3 in the
hands and HPV-6 in the genital region. CONCLUSIONS: The cause of the ICL in this
patient is unknown. HPV is not known to be an immunosuppressive agent; it remains
to be determined whether the HPV-associated lesions are the cause or the result
of immunosuppression.
PMID- 10192161
TI - Detection of Mycobacterium tuberculosis DNA using polymerase chain reaction in
cutaneous tuberculosis and tuberculids.
AB - BACKGROUND: The objective of this study was to explore the role of the polymerase
chain reaction (PCR) fo the detection of Mycobacterium tuberculosis DNA as a
diagnostic aid in cutaneous tuberculosis using routinely processed skin biopsy
specimens. METHODS AND RESULTS: A wide range of clinical specimens representing
different forms of cutaneous tuberculosis and so-called tuberculids were studied.
A sensitive and specific PCR assay targeting the sequence IS6110 of Mycobacterium
tuberculosis complex was used. The specimens were categorized as follows. 1 Acid
fast bacilli (AFB) positive on biopsy (nine specimens from seven patients who
were immunocompromised). PCR was positive in five specimens. Of these, one
specimen was culture positive and three specimens were culture negative. 2 AFB
negative on biopsy: (a) tuberculosis verrucosa cutis (23 specimens); (b) lupus
vulgaris (three specimens); (c) cutaneous tuberculosis clinically suspected (six
specimens). PCR was negative in all specimens. 3 Tuberculids.' (a) erythema
induratum/nodular vasculitis (20 specimens); (b) papulonecrotic tuberculid (two
specimens); (c) erythema nodosum (20 specimens). PCR was negative in all
specimens. CONCLUSIONS: The role of PCR in clinical dermatologic practice, at
this stage, may be in differentiating between cutaneous tuberculosis and atypical
mycobacterial infections in the context of an immunocompromised patient where AFB
can be demonstrated on biopsy and cultures may be negative. In this clinical
situation, PCR allows the prompt diagnosis and early institution of appropriate
therapy. We have not found PCR to be a useful complement to the clinical and
histologic diagnosis of "paucibacillary" forms of cutaneous tuberculosis.
PMID- 10192162
TI - Acne neonatorum: a study of 22 cases.
AB - BACKGROUND: Acne is not uncommon in the neonatal period. Acne neonatorum is
characterized by a mainly facial eruption of inflammatory and noninflammatory
lesions. It is most commonly mild and transient. Hyperactivity of sebaceous
glands, stimulated by neonatal androgens, has been implicated as the underlying
pathogenetic mechanism. MATERIALS AND METHODS: All patients diagnosed with acne
neonatorum in "A. Sygros" Hospital, Athens, Greece, during the years 1993-1996,
were evaluated clinically and epidemiologically. Histologic examination and
smears for Propionibacterium acnes and Pityrosporum ovale were performed in
selected cases. RESULTS: Of the 22 patients studied, 18 were male (81.8%) and 4
were female. The mean age at onset was 3 weeks and the mean duration of the
disease was 4 months. Papules and pustules were the most frequent types of
lesions (72.7%), followed by comedones only (22.7%). The cheeks were the most
common site of predilection (81.8%). A family history of acne was reported in
only three patients. Histologic examination showed hyperplastic sebaceous glands
with keratin-plugged orifices. Smears for P. ovale were negative. CONCLUSIONS:
Our findings are consistent with previous experience, although inflammatory
lesions were encountered more often than previously reported. Hereditary factors
did not seem to play a significant role in our series. Topical treatment hastened
the resolution of this self-limited condition. Recalcitrant cases warrant
investigation for underlying androgen excess.
PMID- 10192163
TI - Benign symmetric lipomatosis in a Chinese man with bullous pemphigoid.
PMID- 10192164
TI - Rosacea induced by beclomethasone dipropionate nasal spray.
PMID- 10192165
TI - Acute rhabdomyolysis and intravascular hemolysis following extensive wasp stings.
PMID- 10192166
TI - Superficial disseminate porokeratosis in a patient with myelodysplastic syndrome.
PMID- 10192167
TI - Bleomycin-induced urticarial flagellate drug hypersensitivity reaction.
PMID- 10192168
TI - Myiasis: a successful treatment with topical ivermectin.
PMID- 10192169
TI - The addition of topical doxepin to corticosteroid therapy: an improved treatment
regimen for atopic dermatitis.
PMID- 10192170
TI - Tretinoin-iontophoresis in atrophic acne scars.
AB - BACKGROUND: Atrophic acne scars are a frequent problem after acne. Hitherto,
mainly invasive treatment measures were possible. In a recent paper, we
demonstrated the positive effects of iontophoresis with 0.025% tretinoin gel vs.
estriol 0.03%. OBJECTIVE: In this further study, the recording of the clinical
effects of iontophoresis with 0.025% tretinoin gel in atrophic acne scars was
supplemented by immunohistochemistry investigations of collagen I and III,
proliferation markers, and the estimation of epidermal thickness. METHODS: The
treatment was performed twice weekly in 32 volunteer patients for a period of 3
months by application of the substance under a constant direct current of 3 mA
for 20 min. Skin biopsies prior to and at the end of treatment were performed in
32 voluntary patients in order to investigate collagen I/III and proliferation
markers by immunohistochemistry methods. RESULTS: Clinically, at the end of
treatment, in 94% of patients a significant decrease in the scar depth was
observed. Neither epidermal thickness nor proliferation markers revealed a
significant increase at the end of treatment. Furthermore, collagen I and
collagen III showed no common trend, as expressed statistically by a lack of
significance. In some cases, increases in collagen III became evident at the end
of treatment. CONCLUSIONS: Tretinoin-iontophoresis is an effective, noninvasive
treatment of atrophic acne scars without causing disturbing side-effects.
PMID- 10192171
TI - The in vitro effect of hydroxychloroquine on skin morphology in psoriasis.
AB - BACKGROUND: In earlier papers, we suggested that the aggravation of psoriasis by
antimalarial drugs (analogous to hypolipidemic drugs) could be initiated by a
break in the epidermal barrier. We suggested that these drugs exerted their
effect by inhibiting epidermal transglutaminase activity, and supported this
hypothesis by demonstrating the effect of hydroxychloroquine sulfate (HCQS) on
the morphology of cultured skin and on liver transglutaminase activity. In the
present article, we describe, for the first time, the morphologic changes induced
by HCQS on cultured skin of psoriatic patients. METHODS: Uninvolved (apparently
normal) skin explanted from the back of two psoriatic patients was cultured in
the presence of 9.2 and 13.8 mM of HCQS for 3 days. The morphologic changes were
evaluated in a blind manner. The experiment was repeated twice. RESULTS:
Significant changes in the epidermal morphology of psoriatic skin cultured in the
presence of HCQS, compared with skin cultured without the presence of the drug,
were observed. The most striking changes were enhanced and irregular
keratinization and dermo-epidermal detachment and cleft formation. No
parakeratosis or other characteristics of psoriasis were observed. CONCLUSIONS:
The first changes caused by HCQS on the cultured skin of psoriatic patients are
not characteristic of psoriasis, and include hyperproliferation and enhanced and
irregular keratinization. The present experimental study gives further support to
the hypothesis that HCQS causes an initial break in the barrier function of the
epidermis (probably by inhibiting transglutaminase activity), which is followed
by a physiologic response of the epidermis aimed at barrier restoration. This
rather nonspecific stimulus to epidermal proliferation is probably sufficient to
trigger psoriasis, in vivo, among genetically predisposed patients.
PMID- 10192172
TI - Effects of UTP on Na+, Cl- and K+ transport in primary cultures from human sweat
gland coils.
AB - Extracellular ATP and UTP can increase membrane permeability in the sweat gland,
but the intracellular signalling regulating the response to these agonists is
poorly understood. Stimulation of Cl- transport by nucleotides has been suggested
as a pharmacological therapy to improve Cl- secretion in patients with cystic
fibrosis. In the present study, regulation of Na+, Cl- and K+ transport in
primary cultures of cells from the secretory coil of human sweat glands was
investigated by electron probe X-ray microanalysis. Stimulation with 200 microM
UTP for 2 min at room temperature caused a significant increase in intracellular
Na but did not affect Cl and K. After 5 min, the Na concentration was still
increased, but now also a significant decrease in Cl and K was observed,
indicating an increase in Cl- and K+ permeability. The effect of UTP on Cl-
secretion was enhanced in Mg2+-deficient buffer, indicating that the response is
elicited by the extracellular fully ionized form of UTP (UTP4+), but not by
MgUTP2+. The effects of UTP were abolished in Ca2+-deficient buffer supplemented
with EGTA. Alloxan, an adenylate cyclase inhibitor, did not inhibit the response
to UTP. These results indicate that the membrane Cl- and K+ permeability elicited
by UTP in primary coil cell cultures is Ca2+-dependent. The response to UTP did
not attenuate at 8 degrees C, suggesting that it could be activated, in part, via
ligand-gated ion channels. The effect of UTP was not decreased in the presence of
ouabain. Pre-treatment of the cells with pertussis toxin (24 h) had minor effects
on Cl- secretion activated by UTP, indicating a role for G proteins in the UTP
activation of Cl- secretion.
PMID- 10192173
TI - Influence of local haemodynamics on leucocyte rolling and chemoattractant-induced
firm adhesion in microvessels of the rat mesentery.
AB - Tissue hyperaemia, oedema formation and leucocyte accumulation are characteristic
features of the inflammatory process referable to changes at the microcirculatory
level. Here, we used intravital fluorescence video microscopy to assess
relationships among haemodynamical parameters, leucocyte rolling, and
chemoattractant-induced firm adhesion in small venules (13-24 microM) of the rat
mesentery. The rolling leucocyte flux in these vessels was directly proportional
to the total leucocyte flux (r = 0.76, P < 0.001), which in turn closely
correlated to the venular blood flow (r = 0.77, P < 0.001). Consequently, the
rolling to total leucocyte flux fraction, averaging 39 +/- 15%, did not vary with
the blood flow and showed no correlation to either blood flow velocity (r =
0.15, P = 0.42) or wall shear rate (r = -0.06, P = 0.77), indicating that the
extent of leucocyte rolling is not primarily dependent on the fluid viscous drag
at physiological blood flow rates in vivo. Stimulation of the mesentery with the
chemoattractant fMLP (10(-6) M) induced firm adhesion of rolling leucocytes. It
was found that the number of adherent leucocytes in individual vessels was
directly related to the rolling leucocyte flux (r = 0.78, P < 0.001) and hence to
the venular blood flow (r = 0.47, P < 0.05), while there was no correlation to
the wall shear rate (r = 0.27, P = 0.24). The dependence of the firm adhesive
response on the blood flow level and the delivery rate of leucocytes was
confirmed at the whole organ level. Thus, leucocyte accumulation in rat skin
lesions was markedly enhanced when a vasodilator was co-administered with the
chemotactic stimulus compared with chemotactic stimulation alone. The data
indicate that, within a physiological blood flow range, the leucocyte response to
chemotactic stimulation is largely independent of the prevailing hydrodynamic
shear forces. Instead, manifestation of the firm adhesive response, because of
its dependence on the preceding rolling interaction, is clearly related to the
blood flow level in the microvessels, which emphasizes the significance of tissue
hyperaemia in inflammation.
PMID- 10192175
TI - Blood oxygen partial pressure affects plasma prolactin concentration in humans.
AB - Responses of plasma prolactin (PRL) concentration to acute and repeated changes
in blood oxygen partial pressure (PO2a) at rest were investigated in two studies
(A; B), with special reference to possible effects mediated via serotonin (5-HT)
synthesis. In A, nine male subjects inhaled for 105 min gas containing different
oxygen fractions for 6 days. Gas concentrations consisted of 14% (A14), 21 %
(A21), 40% (A40), 60% (A60) and 80% (A80) O2 mixed with N2 as well as 100% O2
(A100). Venous and capillary blood samples were drawn before and every 15 min
during gas inhalation for analysis of plasma PRL and PO2a. In B, two groups of
subjects (B I; B II) were exposed to 30 min day(-1) of gas inhalation over 14
consecutive days. Gas concentration consisted for B I of 14% O2/86% N2 and for B
II of 100% O2. During pre- and post-examination a baseline blood sample was
drawn, followed by a neuroendocrine test of serotonergic function using a partial
5-HT1A receptor agonist (60 mg of buspirone hydrochloride). In A, each increase
of inhaled oxygen fraction also resulted in higher blood POb2a. In A14, A21 and
A40, plasma PRL concentrations did not change from basal level. Increases in
plasma PRL concentration were found in A60 after 30 min as well as in A80 and
A100 after 15 min. A higher blood PO2a induced a higher plasma PRL secretion but
also an earlier decline from peak plasma PRL value despite continued inhalation
of the respective oxygen concentration. During post-examination in B, basal
plasma PRL concentrations were increased in B I and decreased in B II. Plasma PRL
response to stimulation challenge was not affected by treatments. Thus, chronic
adaptations of basal plasma PRL concentrations to decreased/increased blood PO2a
were not related to up/down-regulation, respectively, of central serotonergic
receptor function.
PMID- 10192174
TI - Bradykinin elevates cytosolic Ca2+ concentration in smooth muscle cells isolated
from rat duodenum.
AB - The effect of bradykinin on the cytosolic Ca2+ concentration were measured in
single, Fura-2 loaded, smooth muscle cells isolated from rat duodenum. All cells
responded with a Ca2+ signal when exposed to bradykinin. The bradykinin response
consisted of an initial Ca2+ spike followed by a plateau. Pre-treatment of single
muscle cells with either the phospholipase C blocker U-73122 or thapsigargin,
which is a potent inhibitor of the endoplasmic reticulum Ca2+-ATPase, inhibited
the response to bradykinin. Pre-treatment of the cells with EGTA or La3+ to
inhibit the Ca2+ influx, abolished the response induced by bradykinin. We
conclude that bradykinin applied to single smooth muscle cells from rat duodenum,
increases cytosolic Ca2+ by emptying intracellular Ca2+ stores, and by
contribution from extracellular Ca2+. In contrast to bradykinin-induced response
in isolated rat duodenum (a relaxation followed by a contraction), we did not
observe a biphasic effect of bradykinin on cytosolic Ca2+ in single muscle cells.
Bradykinin may thus cause relaxation of duodenal smooth muscle indirectly through
an effect on neighbouring cells as dilatation is brought about by this agent in
blood vessels.
PMID- 10192176
TI - Mechanisms of the relaxant and contractile responses to bradykinin in rat
duodenum.
AB - The signal pathway for bradykinin-induced relaxation followed by contraction in
the isolated rat duodenum was investigated by comparing the effect of blocking
agents on the response to bradykinin and acetylcholine. The phospholipase C
inhibitor U-73122 inhibited the relaxation induced by bradykinin, but had no
effect on the contraction to either bradykinin or acetylcholine. The same
response pattern was observed when the tissues were pre-treated with
thapsigargin, a selective inhibitor of microsomal Ca2+ pumps. An inhibitor of non
voltage-dependent Ca2+ influx, SK&F 96365, inhibited the relaxant response to
bradykinin and the contraction induced by acetylcholine, but not the contraction
induced by bradykinin. In Ca2+-free Krebs-Henseleit buffer, the tissues failed to
respond when they were exposed to either bradykinin or acetylcholine. When the
tissues were partly depolarized (30 mM KCI), both bradykinin and acetylcholine
induced contraction, while the relaxant response to bradykinin was almost
completely abolished. Apamin (an antagonist of low-conductance calcium-activated
K+ channel) together with charybdotoxin (CTX, an antagonist of large-conductance
calcium-activated K+ channel) and CTX alone inhibited the relaxant but not the
contractile response to bradykinin. We conclude that the biphasic response in
isolated rat duodenum to bradykinin involves two distinct pathways. We propose
that the relaxant component is induced indirectly via inositol-mediated increase
in cytosolic Ca2+ in non-muscle cells with subsequent signals to the smooth
muscle cells, whereas the contractile response is induced by direct effect on the
smooth muscle cells.
PMID- 10192177
TI - Vagal stimulation augments maximal (penta) gastrin-stimulated acid secretion in
humans.
AB - Since the late sixties, the pentagastrin test has been the standard method to
examine maximal gastric acid secretion in humans. However, studies on rats and
dogs have shown that maximal pentagastrin-stimulated acid secretion can be
augmented by concomitant cholinergic stimulation. The aim of this study was to
examine whether the combined stimulation of the vagal nerves and pentagastrin
infusion could increase maximal gastric acid secretion compared with pentagastrin
alone. Eight healthy medical students (seven males) were included in the study.
Gastric acid secretion was determined thrice in each subject. On day one,
pentagastrin (6 microg kg(-1) h(-1)) was infused. On day two, insulin-induced
hypoglycaemia (plasma glucose approximately 2.3 mM during 30 min) was obtained by
applying the glucose clamp technique. On day three, pentagastrin infusion and
insulin induced-hypoglycaemia were combined. The combination of insulin-induced
hypoglycaemia and pentagastrin infusion increased peak acid output about 20% (P =
0.018) compared with pentagastrin alone. The hypoglycaemia did not cause
significant release of gastrin. It is concluded that vagal stimulation of gastric
acid secretion may be safely obtained by insulin-induced hypoglycaemia when
applying the glucose clamp technique. In addition, maximal pentagastrin
stimulated acid secretion does not represent the maximal acid secretory capacity
in humans.
PMID- 10192178
TI - Minor redistribution of ventilation and perfusion within the lung during exercise
in sheep.
AB - Considerable heterogeneity unrelated to the effect of gravity has been
demonstrated for both local ventilation (V) and perfusion (Q) in the lung. Local
ventilation and perfusion are well matched, so that the heterogeneity of the V/Q
ratio is less than for ventilation or perfusion alone (Melsom et aL 1997). We are
searching for the mechanisms responsible for the coordinate heterogeneity of
ventilation and perfusion. Here, we ask how and to what extent physical exercise
induces changes in the distribution of ventilation and perfusion. We measured
local (approximately 1.5 cm3 tissue volume) pulmonary ventilation and perfusion
simultaneously in six sheep before, during and after running on a treadmill.
Local ventilation was determined from the deposition of labelled aerosol
particles and local perfusion from trapping of radioactive microspheres. Cardiac
output increased approximately 2.5-fold during exercise. V/Q-ratios were not
normally distributed and we therefore present the heterogeneity as the
interquartile range. At rest, the average interquartile ranges for local
ventilation, perfusion and V/Q-ratio were 0.48, 0.51 and 0.39, respectively.
During exercise, the corresponding values were 0.44, 0.40 and 0.32. Thus, the
distribution of local V/Q-ratio was narrower than for ventilation and perfusion
also during exercise. We found a moderate redistribution of relative flow towards
the dorsal parts of the lungs when perfusion increased, but the increase in total
perfusion and ventilation was for the most part throughout the lung. The results
indicate that the coupling between local ventilation and perfusion is at least as
potent during exercise as at rest. The correlation (r) between paired values in
the two resting periods was 0.93 for ventilation and 0.91 for perfusion and thus
indicates time stability for the two variables.
PMID- 10192179
TI - Catecholamines in pericardial fluid of normotensive, spontaneously hypertensive
and reserpine-treated rats.
AB - In this study our aims were to investigate the presence and source of
catecholamines in pericardial fluid of normotensive, reserpine-treated and
spontaneously hypertensive rats. We found that noradrenaline is the only
detectable catecholamine present in rat pericardial fluid. The effect of
reserpine 6, 12, and 214 h after pre-treatment with 5 mg kg(-1) (8.2 micromol kg(
1)) i.p. shows that the concentration of noradrenaline in pericardial fluid
reflects the amount of noradrenaline released within the heart rather than the
amount of noradrenaline in plasma. Using spontaneously hypertensive rats (SHR) as
a model for primary hypertension we could show that the level of pericardial
noradrenaline is approximately threefold in the pericardial fluid of the SHRs
when compared to respective values of age-matched normotensive Wistar-Kyoto rats
(WKY), suggesting that there was an increased noradrenaline overflow in the
hearts of the SHRs. In conclusion, determination of the noradrenaline
concentration in the pericardial fluid might provide a new method for estimating
the release of noradrenaline in the heart.
PMID- 10192180
TI - Body core temperature during food restriction in rats.
AB - Deep body temperature and locomotor activity of rats fed a reduced food amount (n
= 9) and of starved rats (n = 9), were measured by implanted transmitters. Both
groups were then refed ad libitum. The reduction in body temperature was
significant for both groups, but larger in the starved rats than in the food
restricted rats. There was a displacement of the circadian temperature rhythm in
the starved rats. There were no significant differences in locomotor activity
between groups until the start of refeeding. Rats fed reduced food amounts
rapidly increased their activity, while the starved group retained a low activity
for several days. Thermal conductance was reduced by 30% in both groups. This
reduction in thermal conductance may explain how starving and semistarving rats
are able to maintain core temperatures close to normal, even if resting metabolic
rates are drastically reduced. The measured reduction in body core temperature
signifies a change in the thermoregulatory 'set-point' during starvation.
PMID- 10192181
TI - Regulation of glycogen breakdown by glycogen level in contracting rat muscle.
AB - The interaction of glycogen concentration, insulin and beta-adrenergic
stimulation in the regulation of glycogen breakdown was studied in perfused rat
muscles. Rats were pre-conditioned to obtain two groups with either normal (N) or
'supercompensated' (SC) muscle glycogen. The next day their hindlimbs were
perfused with a medium containing insulin (0, 40 and 100 microU mL(-1)) and/or
isoproterenol (0 and 1.5 nmol L(-1)). Contractions were induced by electrical
stimulation of the sciatic nerve. Compared with N, glycogen breakdown in white
gastrocnemius during contractions was greater in SC at any hormonal combination
(P < 0.05). Conversely, in red gastrocnemius (RG) the higher glycogenolytic rate
in SC, compared with N, faded as the insulin concentration was raised from 0 to
100 microU mL(-1). However, isoproterenol restored the higher glycogenolytic rate
in SC. In any condition, RG glycogen synthase fractional activity was lower (P <
0.05) during contractions in SC than in N. Furthermore, the percentage of
phosphorylase a was higher in SC except when muscles were exposed to insulin
alone. In conclusion, high initial glycogen concentration in fast-glycolytic
muscle causes high glycogenolytic rate during contractions, irrespective of
hormonal stimulation. In contrast, due to down-regulation of phosphorylase
activity, such a relationship does not exist in insulin-stimulated fast-oxidative
muscle.
PMID- 10192182
TI - Jejunal permeability in humans in vivo and rats in situ: investigation of
molecular size selectivity and solvent drag.
AB - The mechanisms controlling rates and routes for intestinal absorption of
nutrients and small compounds are still not fully clarified. In the present study
we aimed to investigate the effect of solvent drag on intestinal permeability of
compounds with different molecular sizes in humans and rats. The effective
intestinal permeabilities (Peff) of hydrophilic compounds (MW 60-4000) were
determined in the single-pass perfused jejunum in humans in vivo and rats in situ
under iso- and hypotonic conditions. The transport mechanism(s) of water and the
importance of the solvent drag effect were investigated by the use of D2O. This
is the first report in humans establishing the relation between in vivo measured
jejunal Peff and molecular size for hydrophilic compounds. In addition, in rats
we also found a molecular-size selectivity for hydrophilic compounds similar to
man. The jejunal Peff of water and urea (MW 60) in both species were several
times higher than predicted from their physicochemical properties. In humans, the
jejunal absorption of urea and creatinine (MW 113) was increased by solvent drag,
while no effect was found for the other investigated compounds. In rats, Peff for
urea and creatinine were unaffected. In conclusion, it is still unclear if
solvent drag occurs mainly through the para- or transcellular route, although,
results from this study further add to our earlier reports suggesting that the
transcellular route is most important from a quantitative point of view
regardless of physicochemical properties of the transported compounds.
PMID- 10192183
TI - Metoprine-induced thirst and diuresis in Wistar rats.
AB - In the present study, the renal responses to metoprine, a histamine-N
methyltransferase inhibitor, were studied in conscious rats. Metoprine (10-20 mg
kg(-1)) or vehicle were administered i.p. to male Wistar rats and the effects
were followed for the subsequent 24 h. It was found that as early as 3 h after
the drug administration metoprine 20 mg kg(-1) had increased water consumption
and urine flow approximately 6-8-fold. The treatment decreased urine osmolality
and increased free water clearance, but caused no change in plasma renin activity
or plasma vasopressin concentration. In addition, a metoprine-induced elevation
in the systolic blood pressure was observed during the first few hours of the
experiment. During the nocturnal period of the study, glomerular filtration rate
and the excretion of electrolytes did not increase in metoprine-treated rats as
they did in control rats. A decrease in the release of atrial natriuretic peptide
was also found. The present results show that inhibition of histamine catabolism
by metoprine causes massive changes in renal functions. It seems to promote water
excretion by the kidneys but, on the other hand, to reduce the excretion of
electrolytes. Although the exact mechanisms, especially the role of increased
blood pressure and nocturnal suppression of atrial natriuretic peptide, require
further clarification, the present data suggest that renin-angiotensin system and
vasopressin were not involved in these renal responses to metoprine.
PMID- 10192185
TI - Anorectal sensation and continence.
PMID- 10192184
TI - Related expression of vascular endothelial growth factor and hypoxia-inducible
factor-1 mRNAs in human skeletal muscle.
PMID- 10192186
TI - Surgical experience improves the long-term results of Nissen fundoplication.
AB - BACKGROUND: Nissen fundoplication relieves symptoms of gastro-oesophageal reflux
and effectively heals oesophagitis. During long-term follow-up some cases of
recurrent reflux are seen. We investigated the possibility that long-term cure of
gastro-oesophageal reflux after fundoplication is influenced by the surgeon's
experience and focused interest, in line with results of surgery for rectal,
gastric, and breast cancer. METHODS: One hundred and five consecutive patients
were evaluated a median of 77 months after open Nissen-Rossetti fundoplication
for erosive oesophagitis. Follow-up included personal interviews and upper
gastrointestinal endoscopy by an investigator not previously involved in the
patients' treatment. The surgeons were classified as experienced (>10 of the
operations in the series), less experienced (<10 operations), or trainees.
RESULTS: Of the most experienced surgeons' patients, 97% had no or at most mild
reflux symptoms at follow-up, compared with 88% of the of less experienced
surgeons' patients (P = 0.04). Healing of erosive oesophagitis was commoner when
the operations were performed by experienced specialist surgeons (88% versus 72%;
P = 0.04). The reoperation rate fell as the surgeons' experience increased, from
12% to 4%. CONCLUSIONS: Surgery for gastro-oesophageal reflux should be
centralized to units specializing in the techniques and with sufficient annual
numbers of operations to optimize results. This policy becomes especially
advisable as laparoscopic surgery increases the numbers of treated patients.
PMID- 10192187
TI - Gastroesophageal reflux in healthy subjects. Significance of endoscopic findings,
histology, age, and sex.
AB - BACKGROUND: Our aim was to evaluate which specific factors are of importance for
the gastroesophageal reflux seen in presumably healthy subjects. METHODS: We
investigated 57 healthy, asymptomatic volunteers with computer-aided medical
history interrogation, endoscopy, biopsy specimens from the distal esophagus,
manometry, and 24-h ambulatory pH-monitoring. RESULTS: Eight subjects (14%)
claimed intermittent reflux symptoms at the computer interview, but they did not
have more acid reflux at pH-monitoring than asymptomatic volunteers. Thirteen
subjects (23%) had abnormalities at endoscopy, 3 of whom had an erosion in the
distal esophagus, and 12 had hiatus hernia. Subjects with hiatus hernia had
increased acid reflux at 24-h pH-monitoring compared with those without hernia.
If subjects with hernia were excluded, the degree of acid reflux was similar in
all age groups. Men had more acid reflux than women, and these differences
persisted if subjects with hernia were excluded. There was no correlation of
histologic signs of esophagitis in the distal esophagus, lower esophageal
sphincter pressure, smoking habit, or body mass index with reflux of acid to the
esophagus. CONCLUSION: Hiatus hernia is a common finding in healthy subjects, and
it predisposes to gastroesophageal acid reflux. Histologic abnormalities are
poorly related to acid reflux in healthy volunteers. We found increased acid
reflux in healthy men compared with women, but larger studies are needed to
confirm these findings. Symptom evaluation is not sufficient to exclude
significant gastroesophageal reflux in healthy volunteers, and we suggest that
the possibility of esophageal abnormalities should be excluded by endoscopy in
comparative studies of gastroesophageal reflux disease.
PMID- 10192188
TI - Activation of apoptotic caspase-3 and nitric oxide synthase-2 in gastric mucosal
injury induced by indomethacin.
AB - BACKGROUND: Apoptosis is the process of programmed cell death characterized by a
series of distinct biochemical and morphologic changes involving activation of
the caspase protease, cascade, which remains under the regulatory control of
nitric oxide. In this study we investigated the activity of a key apoptotic
protease, caspase-3, and the expression of inducible nitric oxide synthase (NOS
2) associated with gastric epithelial cell apoptosis during indomethacin-induced
gastric mucosal injury. METHODS: The experiments were conducted with groups of
rats subjected to intragastric administration of 60 mg/kg indomethacin or the
vehicle. After 2 h the animals were killed and their gastric mucosal tissue used
for macroscopic assessment, assays of epithelial cell apoptosis, and the
measurement of caspase-3 and NOS-2 activities. RESULTS: Indomethacin caused
extensive multiple hemorrhagic lesions accompanied by marked enhancement in
epithelial cell apoptosis, a 3.9-fold increase in mucosal expression of caspase-3
activity, and an 11.9-fold induction in NOS-2. Moreover, the mucosal expression
of NOS-2 showed a positive correlation with the extent of changes induced in
caspase-3 activity. CONCLUSIONS: The results implicate caspase-3 in the process
of indomethacin-induced gastric epithelial cell apoptosis and point towards
participation of NOS-2 in the amplification of the cell death signaling cascade,
hence contributing to the extent of mucosal injury.
PMID- 10192189
TI - Organobismuth compounds: activity against Helicobacter pylori.
AB - BACKGROUND AND METHODS: The antibacterial activity of originally devised and
synthesized organobismuth compounds was tested against fresh clinical isolates of
Helicobacter pylori and compared with clinically well-established inorganic
bismuth salts currently used in triple antibacterial treatment to eradicate H.
pylori. The test conditions in vitro were standard for determination of minimum
inhibitory concentrations (MICs). RESULTS: Organic compounds with covalently
bound bismuth showed stronger and more consistent antibacterial activity than
inorganic bismuth salts. Whereas the most active among the standard therapeutic
inorganic compounds showed MICs against the test organisms of 4-8 mg/l (bismuth
salicylate) and 0.5-64 mg/l, the most active neosynthesized organic substance,
tris(2.6-dimethylphenyl)-bismuthine, consistently showed an MIC of 4 mg/l against
all bacterial strains. CONCLUSIONS: The new line of organobismuth compounds might
offer a therapeutic potential against the bacteria causing peptic ulcer disease.
PMID- 10192190
TI - Role of aging in the expression of Helicobacter pylori gastritis in the antrum,
corpus, and cardia.
AB - BACKGROUND: Earlier studies identified a pylorocardial expansion of chronic
gastritis. We investigated the age-dependent changes in grading and topography of
Helicobacter pylori gastritis. METHODS: Antral, corpus, and cardial biopsy
specimens from 216 H. pylori-positive patients with no peptic ulcer disease
(PUD), malignancy, or Barrett's oesophagus were evaluated with haematoxylin and
eosin and modified Giemsa. The patients were separated into four equal-sized age
groups (1, < 46 years; II, 46-56 years; III, 57-68 years; IV, > 69 years). Sydney
system gradings of bacterial density and activity and degree of gastritis were
used to calculate gastritis sum scores for age- and biopsy site-dependent
comparisons. The prevalence of intestinal metaplasia (IM) and atrophy was also
compared. RESULTS: Mean antral sum scores decreased slightly in group IV but were
higher than those in the corpus or cardia in all groups (P < 0.05 each). In the
corpus mean scores increased in groups II-IV versus group I (P < 0.05 each), and
aging was associated with a significant increase in bacterial density and active
inflammation. The cardia scores remained virtually constant in all groups and
exceeded significantly that in the corpus in group I. IM and atrophy increased
with age, occurring more frequently and earlier in the antrum and cardia than in
the corpus. CONCLUSIONS: Progression of gastritis with age involves the corpus
but not the cardia. Antral inflammation decreases slightly in patients of
advanced age.
PMID- 10192191
TI - Effect of propionibacteria supplementation on fecal bifidobacteria and segmental
colonic transit time in healthy human subjects.
AB - BACKGROUND: Some strains of Propionibacterium have bifidogenic properties and
enhance gut motility in the animal. However, they are not part of the indigenous
fecal flora. This study was designed to assess the digestive survival of ingested
propionibacteria, their bifidogenic properties, and the resulting changes in
colonic transit time in healthy humans. METHODS: Eighteen subjects were given 5 .
10(10) CFU propionibacteria/day during 2 weeks. Fecal concentrations of
propionibacteria and bifidobacteria were counted before (day -8, day -1), during
(day 7, day 14), and after (day 21, day 28) the supplementation. Colonic transit
time was measured before and at the end of the 1st week of supplementation.
RESULTS: Basal counts of propionibacteria were less than 5 log CFU/ml stools.
They increased in 15 subjects to (mean+/-1 standard deviation) 5.63+/-0.71 and
6.37+/-0.89 on day 7 (P < 0.01) and day 14 (P < 0.01) and returned to basal
levels on day 21. Basal counts of bifidobacteria (mean, 7.94+/-0.71) increased to
8.39+/-0.97 on day 7, 8.36+/-0.86 on day 14, and 8.70+/-0.95 on day 21 (P < 0.05
from mean basal count) and returned to pretreatment levels on day 28 (7.88+/
1.38). Mean counts of propionibacteria during supplementation and bifidobacteria
levels on day 14 were significantly correlated (P = 0.01). Transit time did not
change in the right colon (17.4+/-8.1 h versus 17.3+/-8.3 h) or in the
rectosigmoid area(12.8+/-8.5 versus 13.3+/-0.2 h); left colon transit was
significantly slowed (7.0+/-5.0 h versus 11.9+/-9.4 h; P < 0.05). CONCLUSIONS:
Part of the ingested propionibacteria were able to survive the digestive transit.
This supplementation was associated with changes in segmental colonic motility,
yet the mechanisms involved in these changes remain unknown.
PMID- 10192192
TI - Ileal short-chain fatty acids inhibit transpyloric flow in pigs.
AB - BACKGROUND: Short-chain fatty acids (SCFA) found in the ileum after caecoileal
reflux might trigger a physiologic ileal brake similar that induced by ileal
nutrient infusion. This study evaluates gastric emptying and motility after ileal
administration of SCFA. METHODS: In eight conscious pigs gastric emptying was
evaluated by double dilution (liquids) and direct measurement of duodenal
effluent (liquids and solids) during ileal infusions of SCFA and isotonic and
hypertonic saline. Antropyloroduodenal manometry and flow were recorded
concurrently. RESULTS: Ileal SCFA significantly delayed gastric emptying of
liquids and solids. During SCFA infusion the emptying pattern of liquids was less
pulsatile, and flow pulses had a smaller stroke volume than during isotonic
saline. The antroduodenal pressure gradient was decreased, whereas pyloric tone
was increased. A reduced number of antral pressure waves occurred together with
an increased frequency of isolated pyloric pressure waves. CONCLUSIONS: Ileal
SCFA infusion delays gastric emptying of liquid and solid as a consequence of a
decreased antral and increased pyloric motility.
PMID- 10192193
TI - Effects of starvation and bowel resection on paracellular permeability in rat
small-bowel mucosa in vitro.
AB - BACKGROUND: Maintenance of intestinal integrity is essential after major
abdominal surgery in malnourished subjects. The purpose of this experimental
study was to investigate factors affecting small-bowel mucosa permeability in
vitro in the immediate postoperative period in starved rats. METHODS: Male Wistar
rats were randomly placed in five groups: Controls, Anesthesia, Resection,
Starvation, and Starvation + resection. Controls consisted of fed rats.
Anesthesia was induced intraperitoneally with xylazine and ketamine. Resection
was 5 cm of the mid-jejunum, and the starvation period was 48 h. Two hours after
surgery stripped mucosal segments from the jejunum and the ileum were mounted in
Ussing chambers, and the transmucosal permeation of 51Cr-labeled
ethylenediaminetetraacetic acid (EDTA) and dextran (40,000 Da) was studied for
120 min while electrophysiology was monitored. RESULTS: Starvation increased
permeability to 51Cr-EDTA in both the jejunum and ileum. In the jejunum
permeability was further increased by starvation + resection. Resection or
anesthesia alone did not increase permeability. The villous height in the jejunum
was reduced by starvation. Mucosal permeability was correlated to the change in
transepithelial resistance during experiments. CONCLUSIONS: Starvation was the
main cause of increased mucosal permeability in both intestinal segments of the
rat, but surgical trauma had an additive effect, which was most pronounced in the
jejunum.
PMID- 10192194
TI - Wheat starch-containing gluten-free flour products in the treatment of coeliac
disease and dermatitis herpetiformis. A long-term follow-up study.
AB - BACKGROUND: We investigated whether wheat starch-based gluten-free products are
safe in the treatment of gluten intolerance. METHODS: The study involved 41
children and adults with coeliac disease and 11 adults with dermatitis
herpetiformis adhering to a gluten-free diet for 8 years on average. Thirty-five
newly diagnosed coeliac patients at diagnosis and 6 to 24 months after the start
of a gluten-free diet and 27 non-coeliac patients with dyspepsia were
investigated for comparison. Daily dietary gluten and wheat starch intake were
calculated. Small-bowel mucosal villous architecture, CD3+, alphabeta+, and
gammadelta+ intraepithelial lymphocytes, mucosal HLA-DR expression, and serum
endomysial, reticulin, and gliadin antibodies were investigated. RESULTS: Forty
of 52 long-term-treated patients adhered to a strict wheat starch-based diet and
6 to a strict naturally gluten-free diet; 6 patients had dietary lapses. In the
46 patients on a strict diet the villous architecture, enterocyte height, and
density of alphabeta+ intraepithelial lymphocytes were similar to those in non
coeliac subjects and better than in short-term-treated coeliac patients. The
density of gammadelta(+)cells was higher, but they seemed to decrease over time
with the gluten-free diet. Wheat starch-based gluten-free flour products did not
cause aberrant upregulation of mucosal HLA-DR. The mucosal integrity was not
dependent on the daily intake of wheat starch in all patients on a strict diet,
whereas two of the six patients with dietary lapses had villous atrophy and
positive serology. CONCLUSION: Wheat starch-based gluten-free flour products were
not harmful in the treatment of coeliac disease and dermatitis herpetiformis.
PMID- 10192195
TI - Arg506Gln factor V mutation and Val34Leu factor XIII polymorphism in Finnish
patients with inflammatory bowel disease.
AB - BACKGROUND: Earlier studies have indicated that inflammatory bowel disease (IBD),
including Crohn's disease (CD) and ulcerative colitis (UC), is associated with
thromboembolic complications, whereas inherited disorders of coagulation occur
less often than expected in IBD patients. The point mutation Arg506Gln of factor
V (Factor V Leiden), resulting in resistance to activated protein C, is the
commonest inherited form of thrombophilia. Alterations in circulating levels of
factor XIII (FXIII) have been reported among IBD patients. We investigated
whether Factor V Leiden or inherited Val34Leu polymorphism of FXIII would
associate with IBD or its clinical outcome. METHODS: Factor V Leiden mutation and
FXIII Val34Leu polymorphism were assayed in 328 unrelated Finnish patients with
UC and 235 patients with CD by solid-phase minisequencing techniques. The control
groups comprised 142 apparently healthy Finnish subjects and 120 Finnish blood
donors. RESULTS: The frequency of Factor V Leiden mutation among IBD patients
(4.5%) was not significantly different from that in subjects living in the same
area (2.1%). No significant differences could be observed in the FXIII Val34Leu
polymorphism allele frequencies between patients and controls. Clinical features
of IBD, including the disease extent, requirement for immunosuppressive drugs,
and occurrence of complications, seemed to be independent of these two clotting
factor variants analyzed. CONCLUSIONS: Our data do not support an aetiologic or
disease-modifying role for the factor V mutation or factor XIII Val34Leu
polymorphism in IBD.
PMID- 10192196
TI - Significant differences in the interleukin-1beta and interleukin-1 receptor
antagonist gene polymorphisms in a Hungarian population with inflammatory bowel
disease.
AB - BACKGROUND: There is growing evidence of the importance of genetic predisposition
and the activation of the mucosal immune system in the pathogenesis of
inflammatory bowel disease. Thus, genes involved in the regulation of
inflammation are receiving increased attention. We have studied whether Crohn's
disease (CD) or ulcerative colitis (UC) is associated with certain allelic
combinations of IL1B/IL1RA gene polymorphisms in a different European population
than the ones studied so far. METHODS: Ninety-six patients with UC, 97 with CD,
and 132 healthy individuals (HC) were typed for the polymorphic regions in exon 5
of the IL1B gene and in intron 2 of the IL1RA gene, using polymerase chain
reaction-based methods. RESULTS: In CD homozygotes for allele 1 in IL1B gene
polymorphism were more often present (72% versus 28%; P = 0.01) in the subgroup
of patients carrying at least one copy of allele 2 in IL1RA gene polymorphism.
This association was not found in HC (HC versus CD; P = 0.03) or UC. However, in
UC patients with pancolitis a similar trend was observed (75% versus 25%).
Several genotype combinations characterized by the presence of allele 2 of the
IL1RA gene polymorphism were more common in CD (P = 0.001) and UC (P = 0.049)
than in HC. CONCLUSIONS: Our data support the concept that CD and severe UC have
a genetic disequilibrium in the distribution of IL1B and IL1RA gene
polymorphisms. These findings together with functional studies will contribute to
the understanding of the pathogenesis of the chronicity of inflammation in these
diseases.
PMID- 10192197
TI - Long-term results of strictureplasty without synchronous resection for
jejunoileal Crohn's disease.
AB - BACKGROUND: There have been several reports on strictureplasty for Crohn's
disease. However, in most of them the majority of the patients underwent
synchronous bowel resections. The efficacy of strictureplasty has been often
attributed to the synchronous bowel resection. This study was undertaken to
assess the long-term results of strictureplasty alone for jejunoileal Crohn's
disease. METHODS: Forty-three patients who underwent 135 primary
strictureplasties without synchronous resection for jejunoileal Crohn's disease
between 1980 and 1997 were reviewed. Factors affecting reoperation rates were
examined by using a multivariate analysis. RESULTS: There were no operative
deaths. Intra-abdominal septic complications (abscess/fistula) developed in 4
patients (9%). Abdominal symptoms were relieved in all but two patients, who
required further surgery within 6 months after operation. After a median follow
up of 9 years 21 patients (49%) required reoperation for small-bowel recurrence.
A multivariate analysis using Cox's proportional hazard model showed that only
age at operation (<35 years, hazard ratio 11.1 versus >35 years, P = 0.002) was
an independent significant factor affecting the reoperation rate. Sex, duration
of symptoms, smoking, previous small-bowel resection, steroids use, preoperative
nutritional status, and site, number, or length of strictureplasties did not
affect the reoperation rates. At present all the patients are asymptomatic and
receiving neither medical treatment nor nutritional support. CONCLUSIONS:
Strictureplasty is a safe and efficacious procedure for jejunoileal Crohn's
disease in the long term. Only youth was an independent significant risk factor
for recurrence requiring surgery.
PMID- 10192198
TI - Ileal J-pouch--anal anastomosis, sexual dysfunction, and fertility.
AB - BACKGROUND: Our aim was to establish what kind of changes take place in sexual
functions after restorative proctocolectomy and ileoanal anastomosis with J-pouch
(IAA) and whether the operation alters fertility. METHODS: One hundred and ten
consecutive patients who underwent IAA operation for ulcerative colitis at our
institute were sent a questionnaire after at least 2 years' follow-up with
special emphasis on sexual functions. Analysis was made by an independent
researcher. RESULTS: Ninety-five patients (86.7%) responded to the questionnaire.
The mean follow-up of the patients was 71.5 months (range, 30-128 months). The
median age of the 51 women in this study was 39.0 years (range, 23-74 years).
Dyspareunia increased after the operation, but sexual satisfaction improved. The
operation seems to reduce fertility slightly in women, and the rate of
spontaneous abortion may be higher than in the normal population. The median age
of the men was 43.0 (25-69) years. One (2.3%) case of retrograde ejaculation and
six (14.6%) cases of erectile function problems were reported after the
operation. The fear of leakage during coitus were reduced. CONCLUSIONS: Sexual
satisfaction is improved after operation, mainly due to improved general health,
despite minor disturbances in sexual function. There may be a risk of decreased
fertility after restorative proctocolectomy.
PMID- 10192199
TI - Changes in liver-derived enzymes and self-reported alcohol consumption. A 1-year
follow-up study in Denmark.
AB - BACKGROUND: The association between alcohol intake and liver disease is well
known, but little is known about alcohol consumption and changes in liver-derived
enzymes within 1 year. In a 1-year follow-up study we examined changes in liver
derived enzymes and their association with self-reported alcohol consumption.
METHODS: We recorded liver-derived enzyme values, self-reported alcohol
consumption, and potential confounder variables at base line and at a 1-year
follow-up in a representative sample of 822 persons (aged 30-50 years) from the
survey of The Ebeltoft Health Promotion Project in Denmark, by using
questionnaires, health examinations, and blood samples. RESULTS: The prevalence
of increased liver-derived enzyme values was 11.1% at base line and 11.8% at the
1-year follow-up. The incidence rate of increased liver-derived enzyme values was
5.1 per 100 person-years, and 34% of the cases of increased liver-derived enzyme
values returned to normal within I year. We found an odds ratio of 4.0 for men
and 8.0 for women of developing increased liver-derived enzyme values if alcohol
consumption was more than 21 units a week. The risk seemed to be dose-dependent.
CONCLUSIONS: The prevalence of increased liver-derived enzyme values in the
population was high and increased slightly during the study period. There was a
strong association between the incidence rate of increased liver-derived enzyme
values and self-reported alcohol consumption in a dose-dependent relationship,
also when adjusted for confounding by smoking and obesity. The persons with
persistently increased enzyme values had a higher weekly alcohol consumption than
the rest of the study population.
PMID- 10192200
TI - Treatment with interferon-alpha2a alone or interferon-alpha2a plus ribavirin in
patients with chronic hepatitis C previously treated with interferon-alpha2a.
CONSTRUCT Group.
AB - BACKGROUND: Preliminary results from combination therapy with interferon-alpha
and ribavirin (IFN/Rib) in patients with chronic hepatitis C have been promising,
with up to 50% sustained hepatitis C virus (HCV) RNA response. The aim of this
study was to investigate whether a sustained HCV RNA response could be obtained
with combination therapy in patients who were non-responders or relapsers after
IFN treatment. METHODS: In a multicenter study we randomized 53 HCV RNA-positive
patients into 2 treatment groups. They all had biopsy-confirmed chronic hepatitis
C, and all were recruited from a previous IFN study: 26 were previous non
responders and 27 responders with relapse. Group A received interferon-alpha2a,
4.5 MIU thrice weekly for 6 months, and group B received ribavirin, 1000-1200
mg/day, in combination with the same dose of interferon-alpha2a for 6 months.
Median Knodell index was 5.0 in both groups. Genotype 1 was found in 24 (45%),
type 2 in 3 (6%), and type 3 in 26 (49%). RESULTS: Sustained clearance of HCV
viremia 6 months after interferon-alpha2a treatment stop was obtained in 12 of 53
patients (23%): 6 of 27 in the IFN group (22%) and 6 of 26 (23%) in the IFN/Rib
group (NS). Nine of 27 (33%) former responders with relapse, compared with 3 of
26 (12%) non-responders, obtained a sustained HCV RNA response (P = 0.054). In
previous relapse patients sustained loss of viremia was more frequent in genotype
3 (50%) than in genotype 1 (11%) patients (P = 0.022). CONCLUSIONS: In a group of
previous IFN-alpha2a-treated chronic HCV patients we obtained a similar sustained
clearance of viremia when retreated either with IFN-alpha2a alone or with a
combination of IFN-alpha2a and ribavirin for 6 months. Previous relapse patients
with HCV genotype 3 obtained sustained loss of viremia significantly more often
(50%) than type-patients (11%). Previous IFN responders with relapse responded
better than previous non-responders.
PMID- 10192201
TI - Risk of acute pancreatitis in patients with chronic inflammatory bowel disease. A
Danish 16-year nationwide follow-up study.
AB - BACKGROUND: There are few epidemiologic data about the risk of acute pancreatitis
in chronic inflammatory bowel diseases; we therefore wanted to estimate the risk
of a first episode of acute pancreatitis in patients with Crohn's disease and
ulcerative colitis in the total Danish population. METHODS: The study included
all patients discharged from Danish hospitals with a diagnosis of Crohn's disease
or ulcerative colitis registered in the Danish National Registry of Patients in
the period from 1977 to 1992. The first episode of acute pancreatitis was
identified in the cohort. The observed number of patients with acute pancreatitis
was compared with expected numbers on the basis of age, sex, and calendar
specific incidence rates in the general population. RESULTS: Overall, 15,526
patients were discharged and followed up for 112,824 person-years. The
standardized incidence ratio (SIR) for acute pancreatitis was increased both in
patients with Crohn's disease (SIR = 4.3; 95% confidence interval (CI), 2.9-6.1)
and in those with ulcerative colitis (SIR= 2.1; 95% CI, 1.6-2.8). CONCLUSION:
Patients with chronic inflammatory bowel disease seem to be at increased risk of
acute pancreatitis. Further validation and refinement of this registration-based
study are needed.
PMID- 10192202
TI - Comparison of fecal elastase-1 determination with the secretin-cholecystokinin
test in patients with cystic fibrosis.
AB - BACKGROUND: The secretin-cholecystokinin (CCK) test is the gold standard in the
evaluation of exocrine pancreatic insufficiency. Because of its invasive
character, it is of limited value in cystic fibrosis (CF) patients, especially in
those with severe respiratory disease. The aim of the study was to evaluate the
sensitivity of fecal elastase-1 in relation to the secretin-CCK test and
quantitative fecal fat excretion in CF patients. METHODS: The study comprised 28
patients (11 females and 17 males) aged 4 to 20 years. In all patients the
secretin-CCK test and determination of fecal elastase-1 concentration (with
enzyme-linked immunosorbent assay) and fecal fat excretion were performed.
RESULTS: The range of fecal elastase-1 was from undetectable to 485 microg/g
(mean, 84.6+/-119.9 microg/g) and of fecal fat excretion from 1.0 to 55.1 g/day
(mean, 15.0+/-12.2 g/day). On the basis of the results of the secretin-CCK test
(and fecal fat analysis) exocrine pancreatic insufficiency was divided into three
subgroups: mild (I), moderate (II), and severe (III). Four patients were
classified in subgroup I, 4 in II and 20 in III. Fecal elastase (elastase-1)
results were 332.0+/-124.9 microg/g in subgroup I, 96.9+/-45.7 microg/g in
subgroup II, and 32.1+/-41.2 microg/g in subgroup III. The fecal elastase-1
sensitivity with a cut-off point of 200 microg/g was 89.3% for all patients, 100%
for patients in subgroups II and III, but only 25.0% for patients in subgroup I;
the specificity was 96.4%. Linear regression analysis showed a statistically
significant correlation between fecal elastase (elastase-1) and duodenal volume,
bicarbonate, amylase, lipase, and trypsin secretion (in all cases P < 0.001).
CONCLUSIONS: Measurement of fecal elastase-1 is simple and very useful for
assessing the exocrine pancreatic function in CF patients. Elastase is highly
specific in severe and moderate exocrine pancreatic insufficiency, but it is
rather unspecific for milder forms of pancreatic insufficiency.
PMID- 10192203
TI - Interaction of the tyrosine phosphatase inhibitor ortho-vanadate on stimulus-
secretion coupling in pancreatic acinar cells.
AB - BACKGROUND: The effect of the tyrosine phosphatase inhibitor ortho-vanadate on
stimulus-secretion coupling was investigated in isolated rat pancreatic acini.
METHODS AND RESULTS: Ortho-vanadate (10(3)M) reduced cholecystokinin (CCK)-8
(10(10) M)-stimulated amylase release by 40% (IC50 = 5 x 10(4) M). In contrast,
preincubation with 10(3) M ortho-vanadate increased secretin (5 x 10(9) M) and
vasoactive intestinal peptide (VIP) (10(7) M)-induced amylase release by 65% and
80% (IC50= 3 x 10(-4) M), respectively. 8-Bromo-cyclic adenosine-5-monophosphate
(cAMP) (10(-4) M) and phorbol ester (10(-5) M)-induced secretion was increased by
60% and 50%, respectively, whereas thapsigargin-induced amylase release was not
affected. Ortho-vanadate did not affect CCK-8 binding or VIP-induced cAMP
synthesis in isolated acini. In contrast, preincubation with 10(-4) M ortho
vanadate resulted in a significant reduction of CCK-8-induced intracellular
calcium release. In streptolysin-O-permeabilized acini, ortho-vanadate reduced
calcium-induced amlyase secretion by 50%. CONCLUSIONS: The present data provide
indirect evidence of a differential involvement of protein tyrosine
dephosphorylation in both cAMP- and IP3/Ca(2+)-mediated pancreatic secretion. The
differential effects of ortho-vanadate on cAMP- versus calcium-mediated secretion
correspond to the results obtained with receptor-independent intracellularly
acting secretagogues. Further experiments must define the tyrosine phosphatases
involved in both signal-transduction pathways.
PMID- 10192204
TI - Eradication of Helicobacter pylori infection did not lead to cure of duodenal
mucosa-associated lymphoid tissue lymphoma.
AB - Duodenal mucosa-associated lymphoid tissue (MALT) lymphoma is very rare, and
little is known about its clinical course or association with Helicobacter pylori
infection. This report describes the case of a 76-year-old man with a polypoid
mass in the duodenal bulb, diagnosed as low-grade MALT lymphoma. H. pylori
infection in the duodenal mucosa was confirmed by histology with silver stain.
Endoscopic examination showed that the gross lesion regressed after the
eradication of H. pylori despite its histopathologic persistence. Ten months
later, however, cervical and intraperitoneal lymphadenopathy and bone marrow
involvement was observed, and the pathologic diagnosis of the cervical lymph node
was identical with that of the duodenal lesion.
PMID- 10192205
TI - C3 phenotypes and peptic ulcer: association of C3 with peptic ulcer but no
association of C3 with Helicobacter pylori.
PMID- 10192206
TI - The simultaneous treatment of inflammatory bowel diseases and associated pyoderma
gangrenosum with oral cyclosporin A.
PMID- 10192207
TI - Different IL-12p40 responses in hepatitis C virus-induced and alcohol-induced
cirrhosis.
PMID- 10192208
TI - A sex difference and no effect of ApoE type on the amount of cytoskeletal
alterations in the nucleus basalis of Meynert in Alzheimer's disease.
AB - In the nucleus basalis of Meynert (NBM) we studied the presence of early
cytoskeletal alterations as shown by the antibody Alz-50 in ApoE-typed patients.
Using an image analysis system, the area covered by Alz-50 staining and the
percentage of neurons stained by Alz-50 were determined. There were no
significant differences in the area covered by Alz-50 or in the proportion of Alz
50-stained neurons in the nucleus basalis of Meynert of Alzheimer's disease (AD)
patients with one or two ApoE epsilon4 alleles as compared with those without any
ApoE e4 allele. However, there was a significant sex difference in Alz-50
staining: female Alzheimer's disease patients showed more severe early
cytoskeletal alterations than males. We also found a significant relationship
between the number of Alz-50-stained neurons and the severity of dementia.
PMID- 10192209
TI - Metabolic alterations in postmortem Alzheimer's disease brain are exaggerated by
Apo-E4.
AB - Alterations in phospholipid metabolites are a characteristic abnormality of
Alzheimer's disease (AD). Many of these alterations have been demonstrated by
magnetic resonance spectroscopy (MRS) studies of postmortem tissue.
Phosphodiesters appear to be elevated late in the disease and phosphomonoesters
appear to be elevated early in the disease and then decrease. Second to aging,
the most robust risk factor for AD identified to date is the presence of the E4
allele of apolipoprotein-E (Apo-E). Because apolipoproteins are intimately
involved in lipid metabolism, this study was performed to determine if the
presence of the Apo-E4 allele affects the abnormalities in phospholipid
metabolites in AD brain. Perchloric acid extracts from 12 Apo-E 3/3, 31 3/4, 6
4/4 AD brains and 5 Apo-E 3/3 control brains were studied by both proton magnetic
resonance spectroscopy and phosphorus-31 magnetic resonance spectroscopy. When
the E4-positive AD samples were compared with the 3/3 AD samples, an exaggeration
in both phosphomonoester and phosphodiester abnormalities was observed. The
decrease in N-acetyl-L-aspartate (NAA) was also exaggerated. These results
suggest membrane phospholipid metabolite alterations observed in AD are more
severe in the presence of the Apo-E4 allele.
PMID- 10192210
TI - Progression of neurofibrillary changes and PHF-tau in end-stage Alzheimer's
disease is different from plaque and cortical microglial pathology.
AB - In terminal Alzheimer's disease (AD) the frequency of plaques was found to be
reduced in single cases. To test this finding in a larger sample, and in order to
determine whether the number of plaques labeled with different markers and the
distribution of neurofibrillary tangles are correlated positively to each other
and to the degree of dementia, a sample of 134 autopsy brains with and 15 without
AD-related pathology has been examined. All of the cases were staged according to
Braak and Braak. Both the frequency of plaques immunopositive for beta-amyloid,
amyloid precursor protein, and apolipoprotein E and that of microglial cells in
the cortex and in the white matter were determined semiquantitatively. The
content and distribution of PHF-tau was ascertained by ELISA and
immunohistochemistry. Both the clinical dementia rating and the global
deterioration scale were used as clinical parameters retrospectively. Correlation
coefficients were calculated for all parameters and differences were evaluated
statistically. With progressive distribution of neurofibrillary tangles and
increasing content of PHF-tau the plaque stages and the degree of cortical
microglia reaction increased up to the Braak-stages IV and V, thereafter showing
a slightly decreasing tendency in the investigated regions. In end-stage AD
resorption of beta-amyloid seems to surpass its deposition. The microglial
reaction in the white matter correlated neither with the Braak-stage nor with the
accumulation of amyloid. With regard to the degree of dementia, both scales
correlated well with the pathological changes. Our data show that neuronal
cytoskeletal alterations progressively increase with progressive dementia until
the end stage of AD in contrast to the frequencies of plaques and cortical
microglial cells, and are therefore preferable for staging purposes.
PMID- 10192211
TI - TGF-beta receptors-I and -II immunoexpression in Alzheimer's disease: a
comparison with aging and progressive supranuclear palsy.
AB - The transforming growth factor-betas (TGF-betas) influence cell survival, and TGF
beta2 shows increased immunoexpression in neurofibrillary tangle-bearing neurons
and reactive glia in Alzheimer's disease (AD) and progressive supranuclear palsy
(PSP). We compared immunohistochemical expression of TGF-beta type I (RI) and
type II (RII) receptors in eight patients with AD, eight controls and three cases
of progressive supranuclear palsy. Mild intraneuronal immunoreactivity for the RI
receptor was observed in all cases. Intraneuronal TGF-beta RII receptor
immunoexpression was more common in all groups, and its frequency did not differ
between groups. We observed increased immunoreactivity for both RI and RII
subtypes in reactive glia in the AD frontal cortex (RI: U = 0.5, p = 0.002; and
RII: U = 9.000, p = 0.006) and parahippocampal gyrus (RI: U = 9.500, p = 0.013;
RII: U = 14.5, p = 0.05) compared to control cases. We conclude that TGF-beta RI
and II immunoreactivity is increased in reactive glia in AD and progressive
supranuclear palsy, and RI immunoreactivity may occasionally be increased in
neurons in cases with advanced AD.
PMID- 10192212
TI - Postmortem changes in the phosphorylation state of tau-protein in the rat brain.
AB - The phosphorylation state of tau-protein is crucial for the regulation of
neuronal microtubule organization. Functional conclusions on tau-protein require
an accurate assessment of phosphorylated sites. Therefore, the in vivo
distribution and postmortem preservation of some phospho-epitopes on tau-protein
were examined in the rat brain under different fixation and preparation
conditions. Detection of tau-protein with a phosphorylation-independent antiserum
revealed both axonal and somatodendritic localizations, which were not influenced
by a postmortem interval of 30 min. The phospho-epitopes recognized by 12E8, AT8,
and PHF-1 were mainly localized in the somatodendritic compartment. The binding
sites of AT8 and PHF-1 were rapidly dephosphorylated postmortem, whereas the Tau
1 epitope was unmasked in the somatodendritic region. The axonally located
phospho-epitope of AT270 and the nuclear epitope of AT100 were still detectable
after a postmortem interval of 30 min. Postmortem dephosphorylation and
inhibition of this process by PP1 and/or PP2A was further demonstrated on Western
blot. In conclusion, rapid processing of tau-protein is essential for the correct
assessment of investigations on phospho-isoforms.
PMID- 10192213
TI - Changes in behavior and muscarinic receptor density after neonatal and adult
exposure to bioallethrin.
AB - Throughout life, mammals are exposed to environmental toxicants, some of which
have acute effects on the nervous system. Early, low-dose exposure in combination
with later re-exposure and possible interference with normal aging have been
little studied. The present study revealed increased susceptibility in adult
mice, exposed neonatally to a low dose of the insecticide bioallethrin, to
renewed exposure to bioallethrin as adults. Ten-day-old Naval Medical Research
Institute male mice received bioallethrin orally (0.7 mg per kg body weight per
day for 7 days). When aged 5 months they were given the same dose of bioallethrin
by gavage. Twenty-four hours after the last administration, a spontaneous motor
activity test revealed significant aberrations in mice exposed both neonatally
and as adults to bioallethrin. The density of muscarinic receptors was
significantly increased. When aged 7 months, spontaneous behavioral disturbances
and muscarinic receptor changes persisted and learning and memory deficits had
developed. These results indicate that neonatal exposure to bioallethrin has the
potential to increase susceptibility of the adult mouse to a new exposure at a
dosage that does not have any effect in animals treated neonatally with vehicle.
PMID- 10192214
TI - Differential expression of muscarinic subtype mRNAs after exposure to neurotoxic
pesticides.
AB - We have recently reported an increase in the density of muscarinic cholinergic
receptors in mice neonatally exposed to a persistent environmental agent,
dichlorodiphenyltrichloroethane (DDT), and a subsequent exposure as adults to
nonpersistent toxicants, such as bioallethrin or paraoxon. Here we have examined
the effects of an exposure like this on muscarinic receptor mRNA expression. Ten
day-old Naval Medical Research Institute mice received a single oral dose of DDT
(0.5 mg/kg body weight). When aged 5 months, they received bioallethrin (0.7
mg/kg body weight per day for 7 days) or paraoxon (1.4 mg/kg body weight every
second day for 7 days). mRNA expression of subtypes m1, m3, and m4 was studied in
7-month-old animals. Changes could only be discovered in the DDT-bioallethrin
treated mice, where expression of subtype m4 was elevated in cortex and caudate
putamen. Moreover, the expression pattern of the subtypes m1, m3, and m4 in mouse
brains was found to be very similar to that seen in rats, except for slight
differences in the pyramidal cell layer of the hippocampus, where the outermost
part of the CA3 region did not show any m4 hybridization. The present study
indicates that the earlier observed increase in muscarinic receptor density in
mice exposed as neonates to DDT and as adults to bioallethrin can be attributed
to changes in the expression of m4.
PMID- 10192215
TI - Age-related toxicity to lactate, glutamate, and beta-amyloid in cultured adult
neurons.
AB - The age-related susceptibility of the brain to neurodegenerative disease may be
inherent in the susceptibility of individual neurons to various stressors.
Neurons were isolated from embryonic, young- and old-aged rat hippocampus,
cultured in serum-free medium and exposed to lactic acid, glutamate or beta
amyloid. Yields of isolated adult cells were 1 million cells/hippocampus, 12,000
cells/mg tissue, independent of age. For lactic acidosis, there was a non
significant 10% increment in killing of neuron-like cells from old rats compared
to young. For glutamate, there was a 5-10% increment in killing of neuron-like
cells from old rats compared to young rats and embryonic neurons. For cells
exposed to the toxic fragment of beta-amyloid, A beta (25-35), toxicity was age,
dose and time-dependent. Maximum toxicity in cells treated for 1 day with 25
microM A beta (25-35) was 16%, 24%, and 33% for embryonic, young and old cells.
Similar results were found for A beta (1-40) (LD50 = 2 microM). These results
suggest that aging imparts to individual cells an increased susceptibility to
toxic substances relevant to neurodegenerative diseases.
PMID- 10192216
TI - Age-related susceptibility to 3,3'-iminodipropionitrile-induced olfactory mucosal
damage.
AB - 3,3'-Iminodipropionitrile (IDPN) causes degeneration of the olfactory mucosa (OM)
in rodents following systemic exposure. Approximately 30% of the OM degenerates
in 21-day- and 10-week-old rats following a single 200 or 400 mg/kg
intraperitoneal (i.p.) dose of IDPN, whereas 100% olfactory mucosal degeneration
occurred in 21-month-old rats. Age-related changes in the flavin-containing
monooxygenases (FMOs) or heat shock protein 70 (HSP70) were hypothesized to be
responsible for altered olfactory mucosal susceptibility to IDPN. FMO activity in
OM was higher than in liver in rats up to 40 weeks of age. Western blots of OM
and liver revealed no change in FMO1 protein; however, FMO2, 3, and 5 decreased
in olfactory microsomes with age. FMO3 and FMO5 increased in liver microsomes
with age. Heat shock protein 70 did not differ between 10-week- and 10-month-old
rats in either tissue. The mechanism underlying the increased susceptibility of
older rats is likely a complex interaction between the activities of one or more
of the enzymes involved in IDPN metabolism in OM and liver.
PMID- 10192217
TI - Regulation of intracellular Ca2+ concentration by interleukin-1beta in rat
cortical synaptosomes: an age-related study.
AB - The pro-inflammatory cytokine interleukin-1beta (IL-1beta) is released by cells
during injury and stress, and increased neuronal expression of IL-1beta is a
feature of age-related neurodegeneration. We have recently reported that IL-1beta
has a biphasic effect on the K+-induced rise in intracellular Ca2+ concentration
([Ca2+]i) in cortical synaptosomes, exerting an inhibitory effect on the K+
induced rise in [Ca2+]i at lower (3.5 ng/mL) concentrations and a stimulatory
effect on the K+-induced rise in [Ca2+]i at higher (100 ng/mL) concentrations. In
the present study, we observed that the K+-induced rise in [Ca2+]i was inhibited
to a similar extent by the lower concentration of IL-1beta in cortical
synaptosomes prepared from young (3-month-old), middle-aged (12-month-old) and
aged (24-month-old) rats. In contrast, cortical synaptosomes prepared from the
aged rats exhibited an increased susceptibility to the higher concentration of IL
1beta, resulting in a marked elevation in [Ca2+]i. We propose that the age
related increase in neuronal concentration of IL-1beta promotes a dramatic
elevation in [Ca2+]i following membrane depolarization, thereby altering Ca2+
homeostasis and exacerbating neuronal vulnerability to excitotoxicity.
PMID- 10192218
TI - Up-regulation of alpha1D Ca2+ channel subunit mRNA expression in the hippocampus
of aged F344 rats.
AB - There is growing evidence that alterations in calcium (Ca2+) homeostasis may play
a role in processes of brain aging and neurodegeneration. There also is evidence
that some of the altered Ca2+ homeostasis in hippocampal neurons may arise from
an increased density of L-type voltage sensitive Ca2+ channels (L-VSCC). In the
present studies, we tested the possibility that previously observed increases in
functional L-VSCC with aging might be related to up-regulated gene/mRNA
expression for Ca2+ channel subunits. A significant aging-related increase in
mRNA content for the alpha1D subunit of the L-type VSCC was observed in
hippocampus of aged F344 rats (25 months old) relative to young (4 months old)
and middle-aged animals (13 months old), as assessed by both in situ
hybridization analyses (densitometry and grain density) and ribonuclease
protection assay (RPA). In RPA analyses, the alpha1C subunit mRNA also showed a
significant increase in 25-month-old rats. No age changes were seen in mRNA for
the beta1b subunit of VSCC or for GAPDH, a standard control. The clearest
increases in alpha1D mRNA expression were observed in subfield CA1, with little
or no change seen in dentate gyrus. Although these results alone do not
demonstrate that mRNA/gene expression changes contribute directly to changes in
functional Ca2+ channels, they clearly fulfill an important prediction of that
hypothesis. Therefore, these studies may have important implications for the role
of gene expression in aging-dependent alterations in brain Ca2+ homeostasis.
PMID- 10192219
TI - Environmental influences on cognitive decline in aged rats.
AB - Two experiments are reported in which young and old rats, housed in an
impoverished (IE), enriched (EE), or standard (SE), environment, were tested on a
series of complex, blind-alley mazes. In Experiment 1, 3-months exposure to IE
exacerbated age differences in maze performance, relative to the differences
between young and old rats in EE and SE. Old rats in the EE and SE conditions did
not differ from each other. In Experiment 2, rats were raised for an additional 3
months in either IE or EE before further maze testing. The main findings were
that the maze performance of old rats, transferred from IE to EE, improved
significantly, whereas the performance of old rats, transferred from SE or EE to
IE, declined. These results indicated that the deleterious effects of an
impoverished environment on learning and memory are, at least partly, reversible,
and that experience in a stimulating environment can protect old rats from the
adverse effects of relocation to a deprived environment. Taken together, the
results highlight the impact of environmental influences on cognitive function in
old age, and emphasize the need to consider nonbiological factors in
understanding the process of cognitive aging.
PMID- 10192220
TI - Hippocampal neuron and synaptophysin-positive bouton number in aging C57BL/6
mice.
AB - A loss of hippocampal neurons and synapses had been considered a hallmark of
normal aging and, furthermore, to be a substrate of age-related learning and
memory deficits. Recent stereological studies in humans have shown that only a
relatively minor neuron loss occurs with aging and that this loss is restricted
to specific brain regions, including hippocampal subregions. Here, we investigate
these age-related changes in C57BL/6J mice, one of the most commonly used
laboratory mouse strains. Twenty-five mice (groups at 2, 14, and 28-31 months of
age) were assessed for Morris water-maze performance, and modern stereological
techniques were used to estimate total neuron and synaptophysin-positive bouton
number in hippocampal subregions at the light microscopic level. Results revealed
that performance in the water maze was largely maintained with aging. No age
related decline was observed in number of dentate gyrus granule cells or CA1
pyramidal cells. In addition, no age-related change in number of synaptophysin
positive boutons was observed in the molecular layer of the dentate gyrus or CA1
region of hippocampus. We observed a significant correlation between dentate
gyrus synaptophysin-positive bouton number and water-maze performance. These
results demonstrate that C57BL/6J mice do not exhibit major age-related deficits
in spatial learning or hippocampal structure, providing a baseline for further
study of mouse brain aging.
PMID- 10192221
TI - NSAIDs and incident Alzheimer's disease. The Rotterdam Study.
AB - Recent studies suggest that the use of nonsteroidal anti-inflammatory drugs
(NSAIDs) may reduce the risk for Alzheimer's disease (AD). We investigated the
relation of NSAID use over a 10-year period and the risk for incident AD using a
nested case-control design in the population-based Rotterdam Study. The study was
performed in 306 subjects; 74 Alzheimer patients diagnosed according to NINCDS
ADRDRA criteria and 232 age and sex-matched controls. NSAID use was abstracted
from general practitioners' medical records and expressed as cumulative
prescription days. The relative risk for AD associated with long-term use (> or =
2 months) was 0.95 (95% CI: 0.46-1.99) as compared to nonusers, after controlling
for possible confounders. In a separate examination, subjects who had more than 6
months of prescription days had a reduced relative risk for AD (RR = 0.74 (95%
CI: 0.20-2.72). In an age-stratified analysis the effect in long-term users was
evident in those aged 85 and under; 0.53 (95% CI: 0.15-1.77). All risk estimates
were lower when the last 2 years of exposure were excluded from the analyses. Our
point estimates in subjects younger than 85 years and in subjects using NSAIDs
for 6 months or more are consistent with the hypothesis that long-term use of
NSAIDs reduces the risk for AD. However, overall there was no association between
NSAID use and the risk for incident AD.
PMID- 10192222
TI - Exposure classification: the bugbear of dementia epidemiology.
PMID- 10192223
TI - New findings consistent with Alzheimer's-NSAIDs link.
PMID- 10192224
TI - Pro-inflammatory complement activation by the A beta peptide of Alzheimer's
disease is biologically significant and can be blocked by vaccinia virus
complement control protein.
AB - The amyloid plaque is the hallmark of Alzheimer's disease (AD). The transmembrane
domain and a portion of the C-terminus (A beta) of the amyloid precursor protein,
are known to form the nucleus of the amyloid plaque. It has been demonstrated
recently, using in vitro assays, that the A beta peptide can activate both the
classical (antibody-independent) and alternate pathways of complement activation.
The proposed complement activation is due to the binding of A beta to the
complement components C1q and C3, respectively, which initiate formation of the
proinflammatory C5a and C5b-9 membrane attack complex. In this report, we have
investigated the in vitro findings for the likely complement-dependent
proinflammatory properties of the Alzheimer's disease A beta peptide. We have
performed experiments using congenic C5-deficient and C5-sufficient mice injected
with synthetic A beta and recombinant polypeptide (C-100) containing A beta.
Injection of C-100 into C5-sufficient mice induced a clear increase in the number
of polymorphonuclear cells (neutrophils) at the site of injection due to
complement activation and the subsequent release of proinflammatory chemtoactic
factors. In sharp contrast, the C5-deficient mice did not show any increase in
cellular influx. The vaccinia virus complement control protein, an inhibitor of
both the classical and alternate pathway can down-regulate the biologically
significant activation of complement by A beta, as demonstrated by an in vitro
immunassay. The therapeutic down-regulation of A beta-caused complement
activation could greatly alleviate the progression of some of the chronic
neurodegeneration characteristic of Alzheimer's disease.
PMID- 10192225
TI - Isolated clinic hypertension is not an innocent phenomenon: effect on the carotid
artery structure.
AB - This study examines the common carotid intimal-medial wall thickness (CCA-IMT) in
untreated patients with elevated clinic blood pressure (BP) but normal ambulatory
BP (isolated clinic hypertension, n = 22), in comparison with a group with
elevated clinic and ambulatory BP (hypertensives, n = 41) and a group with normal
clinic and ambulatory BP (normotensives, n = 17) readings. The three groups did
not differ in age, male/female ratio, lipid profile, glucose tolerance test, or
smoking habits. No difference existed in CCA-IMT values between the groups with
hypertension (0.67 +/- 0.18 mm) and isolated clinic hypertension (0.68 +/- 0.14
mm), but the values in these two groups were significantly higher (one-way ANOVA;
F = 8.09, P < .001) than in the group of normotensives (0.50 +/- 0.09 mm). The
CCA-IMT did not correlate with clinic systolic or diastolic BP readings or with
BP derivatives of 24-h ambulatory monitoring. Mean 24-h BP in the isolated clinic
hypertensives did not differ from that in the normotensives, whereas both were
lower than in the hypertensives. We conclude that changes in the CCA-IMT occuring
in subjects with isolated clinic hypertension are equal to the changes in
sustained hypertension, indicating that isolated clinic hypertension may not be a
benign condition.
PMID- 10192226
TI - Frequency and determinants of white coat hypertension in mild to moderate
hypertension: a primary care-based study. Monitorizacion Ambulatoria de la
Presion Arterial (MAPA)-Area 5 Working Group.
AB - Most of the previous studies on white coat hypertension were performed in
hypertension clinics or academic settings and included relatively small series of
patients. Consequently, the prevalence of white coat hypertension in primary care
settings and the clinical and epidemiologic characteristics of this subgroup of
patients are not well known. We performed this study to estimate the frequency of
white coat hypertension in a population of mildly to moderately hypertensive
subjects attended in a primary care setting and to examine possible epidemiologic
and clinical factors that may identify these patients. Patients included in the
study underwent clinical interview, measurement of clinic blood pressure (BP) on
three visits, determination of serum lipids, glucose, uric acid, and urinary
albumin excretion, 24-h ambulatory BP monitoring, and M-mode and Doppler
echocardiography. Patients were classified as white coat hypertensives if their
daytime ambulatory BP were < 135/85 mm Hg. We studied 345 patients, 136 (39%) of
whom were diagnosed with white coat hypertension. The frequency of white coat
hypertension was inversely proportional to the severity of clinic BP values. The
diagnosis of white coat hypertension was independently associated with female
gender and low educational level. Left ventricular mass index and urinary albumin
excretion were lower in the white-coat hypertensive group compared with the group
with sustained hypertension. Our results show that a high proportion of patients
with mild to moderate hypertension attended in a primary care setting have white
coat hypertension. Some clinical characteristics may be helpful in the
identification of this group of subjects. White coat hypertensives show less
target-organ damage than sustained hypertensive patients.
PMID- 10192227
TI - Family history of essential hypertension versus obesity as risk factors for
hypertension in adolescents.
AB - Family history of hypertension and obesity are both risk factors for
hypertension. Hypertension and obesity share several physiopathologic
abnormalities and are frequently associated. However, not all obese people are
hypertensive. Renal handling of sodium has been proposed as a physiopathogenic
mechanism of essential hypertension and obesity. This study was conducted in
obese adolescents to evaluate the role of a family history of hypertension versus
obesity in the renal handling of sodium. Fractional excretion of lithium (FELi)
and uric acid (FEUA) were measured in 46 obese adolescent offspring of
hypertensive parents (OH: body mass index [BMI], 29.5 +/- 0.6 kg/m2, age 14.2 +/-
0.3 years, 22 males); eight obese offspring of normotensive parents (ON: BMI,
30.7 +/- 1.7 kg/m2, 14.8 +/- 0.8 years, four males), and in 34 lean adolescent
offspring of hypertensive parents (LH: BMI, 20.5 +/- 0.5 kg/m2, 14.3 +/- 0.3
years, 24 males). FELi in OH was 16.5% +/- 1.3%, in ON it was 22.4% +/- 2.3%, and
in LH it was 14.4% +/- 1.2% (P < .05). FEUA in OH was 8.5% +/- 0.8%, in ON it was
14.8% +/- 3.6%, and in LH it was 7.9% +/- 0.8% (P < .01). Plasma renin activity
(PRA) and aldosterone (PA) were measured in OH and LH; PRA was 5.3 +/- 0.4 and
4.5 +/- 0.4 ng/mL/h, respectively (P = NS), and PA was 366 +/- 36 and 242 +/- 32
pg/mL, respectively (P < .05). In summary, adolescents with a family history of
hypertension, regardless of their body mass, have a diminished FELi and FEUA.
Obese adolescents also have higher plasma levels of aldosterone than lean ones.
In conclusion, the family history of hypertension would be related to the
increased renal proximal sodium reabsorption whereas obesity would be related to
increased distal sodium reabsorption mechanisms, such as aldosterone. Both
mechanisms could explain the higher prevalence of hypertension in obese offspring
of hypertensive parents.
PMID- 10192228
TI - Familial aggregation of resting blood pressure and heart rate in a sedentary
population: the HERITAGE Family Study. Health, Risk Factors, Exercise Training,
and Genetics.
AB - The familial aggregation of resting systolic blood pressure (SBP), diastolic
blood pressure (DBP), and heart rate (HR) was assessed in 98 white families, who
participated in the HERITAGE Family Study, and were selected to be sedentary, and
primarily nonobese and normotensive. In the present study, 522 family members
were sedentary at baseline examination, and resting SBP, DBP, and HR measured
during this examination were investigated. If physical activity level is a potent
environmental factor, then we expected that the relative contribution of
environmental factors to the familial aggregation of blood pressure (BP) would be
somewhat reduced, because activity was controlled for in this study. Using a
familial correlation model, maximal heritabilities were estimated to be 54%, 41%,
and 32% for resting SBP, DBP, and HR, respectively, in these families; and they
were 51%, 42%, and 34% for resting SBP, DBP, and HR, respectively, when the data
were adjusted for body mass index. The estimates are somewhat higher for BP but
similar for HR to those reported in previous family studies, suggesting that the
distribution of the underlying etiologic factors in these sedentary families may
be similar to those in the general population. There was substantial spouse
resemblance in this study, which may be explained by a higher concordance for
correlated lifestyle factors including diet, similar activity levels, or by
assortative mating for relative weight or dietary preferences.
PMID- 10192229
TI - The prevalence and etiology of impotence in 101 male hypertensive outpatients.
AB - Erectile dysfunction and impotence has a high prevalence among male hypertensive
patients. Whether this relates mainly to specific drug side effects or to primary
pathogenic disorders is unknown. In the present study 101 male patients from our
outpatient hypertension clinic answered detailed questionnaires about
hypertension and sexual function. Patients with perceived impotence were offered
a thorough penile evaluation and examination performed by specialists in the
urology department. Twenty-seven (27%) men had impotence. The main cause of
impotence was an arterial dysfunction (89%). The prevalence of impotence was
related to the degree of secondary organ manifestation, reflected by World Health
Organization (WHO) classification I-III (P = .01). Intermittent claudication (P =
.001) and ischemic heart disease (P = .005) were the best determinants in this
respect. Twelve impotent patients (44%) ascribed onset of impotence to drug
initiation. A variety of drugs were incriminated in the occurrence of drug
induced impotence. In summary our results indicate that impotence in hypertensive
men is caused mainly by penile arterial vascular changes, probably
atherosclerosis. Drug-induced impotence could well be the result of blood
pressure reduction itself and not specific drug side effects.
PMID- 10192230
TI - Higher cholesterol and insulin levels in pregnancy are associated with increased
risk for pregnancy-induced hypertension.
AB - Hyperinsulinemia and dyslipidemia are known to be associated with essential
hypertension but their role in pregnancy-induced hypertension remains unclear. We
performed a case-control study comparing cholesterol, insulin, and glucose levels
in the early third trimester of pregnancy among 31 women who developed pregnancy
induced hypertension (PIH) (either preeclampsia [n = 6] or nonproteinuric
gestational hypertension [n = 25]), with 31 women remaining normotensive through
pregnancy. As compared with women remaining normotensive, women subsequently
developing PIH had higher fasting cholesterol levels (279 v 247 mg/dL; P = .02)
and higher fasting insulin levels (13.3 v 7.9 microU/mL; P = .03), although
fasting glucose levels and levels of glucose and insulin after glucose load did
not differ significantly between groups. In comparing hypertensive subgroups,
fasting insulin levels were significantly higher among women who subsequently
developed preeclampsia, but not among those subsequently developing
nonproteinuric gestational hypertension. Although women developing PIH had higher
pregravid body mass index (25.1 v 22.6 kg/m2, P = .06), fasting cholesterol and
insulin levels were associated with risk for PIH even after adjustment for body
mass index and age (relative risks for one unit increase, respectively: 1.02 (P =
.03) and 1.12 (P = .03). Higher fasting cholesterol and insulin levels in mid- to
late pregnancy are associated with increased risk for PIH. These observations
support a role for insulin resistance in the development of this complication of
pregnancy.
PMID- 10192231
TI - Can insulin action induce myocardial texture alterations in essential
hypertension?
AB - The prevalence of hyperinsulinemia/insulin resistance in hypertensive
individuals, as well as the effects of insulin on myocytic and fibroblastic
growth, are well known in both epidemiologic and animal models. To check whether
there are any links between ultrasonic myocardial texture parameters and insulin
level in essential hypertensives, we compared 18 essential hypertensive men
(Group 1, H) with 18 age- and gender-matched healthy controls (Group 2, C) (age,
57 +/- 10 years). For all study subjects we performed ambulatory blood pressure
monitoring (ABPM); conventional 2-D Doppler echocardiography for the assessment
of the left ventricular mass index (LVMi) and function; quantitative analysis of
digitized echocardiographic images for evaluation of cyclic variation (CVI) of
mean gray level (MGL) at the septum and posterior wall levels; and 75-g 3-h oral
glucose tolerance test (OGTT) for analysis of area under glycemic curve (AUGC,
g/min/dL) and insulinemic curve (AUIC, mU/min/mL), as well as serum glucose and
insulin peaks. Both the daily mean blood pressure (H: 109 +/- 4.6 v C: 94.6 +/-
4.6, P < .0001) and LVMi (adjusted for body surface) (H: 133 +/- 24 v C: 97 +/-
21 g/m2, P < .0001) were significantly higher in hypertensives. Values for AUIC
were significantly higher in hypertensives (10.37 +/- 5.53 v 6.33 +/- 5.28), P <
.032); CVI was also significantly higher in group C, for both septum (C: 40.2 +/-
16.9 v H: 15.9 +/- 18.1, P < .0001) and posterior wall (C: 44.5 +/- 19.6 v H: 20
+/- 17.5; P < .0001). There was a significant inverse correlation between AUIC
and CVI for both septum (r: -0.57, P < .001) and posterior wall (r: -0.50, P <
.002). The significantly higher impairment of myocardial ultrasonic texture and
the higher level of the AUIC insulinemia in hypertensives, as well as the
significant inverse relationship between CVI and hyperinsulinemia, are our major
findings. Hyperinsulinemia/insulin resistance could cause an altered
collagen/muscular ratio, which could potentially explain, at least in part, the
CVI alterations detected in hypertensive patients.
PMID- 10192232
TI - Angiotensin I converting enzyme gene polymorphism and insulin resistance in
patients with angina pectoris.
AB - The association between insertion/deletion polymorphism of the angiotensin I
converting enzyme (ACE) gene and insulin resistance (IR) was investigated in 64
consecutive patients (F/M: 11/53) with angina pectoris without clinically
manifest diabetes mellitus who underwent diagnostic coronary angiography. The
observed frequency distribution of ACE genotypes did not deviate from that
predicted from the Hardy-Weinberg equilibrium in this group. Patients with the
ACE-ID genotype had significantly lower IR, as assessed by an oral glucose
tolerance test (OGTT) and by homeostatic model assessment (HOMA), compared to
those with the ACE-II genotype, as assessed by a multiple comparison analysis.
Patients were divided into two groups with low and high HOMA-IR, and the I allele
was seen more frequently in the high HOMA-IR group than in the low HOMA-IR group
(0.62 v 0.47, respectively, by chi2 test, P < .05). Logistic regression analysis
showed that the odds ratio for insulin resistance in patients with the II
genotype, compared to those with the ID and DD-genotypes (assuming that the I
allele has a recessive effect), was 4.0 (95% confidence interval, 1.2 to 16.5; P
= .037), after adjusting for the presence of significant coronary
atherosclerosis. In conclusion, the D allele was not associated with higher
insulin resistance in patients with angina pectoris; that is, patients with the
ID and DD genotypes were associated with a significantly lower risk of insulin
resistance, compared to those with the II genotype.
PMID- 10192233
TI - A double blind comparison of the effects of amlodipine and enalapril on insulin
sensitivity in hypertensive patients.
AB - This study compares the effects of a calcium channel blocker (amlodipine) and an
angiotensin converting enzyme inhibitor (enalapril) on in vivo insulin
sensitivity in patients with essential hypertension. Forty-six patients with mild
and moderate hypertension were studied. After a 2-week single-blind placebo
phase, they were randomly assigned to double-blind therapy with either amlodipine
(2.5 to 10 mg/day) or enalapril (5 to 40 mg/day) for 16 weeks. Both groups were
comparable in terms of demographic characteristics, degree of obesity, metabolic
parameters, and arterial blood pressure. Insulin sensitivity was measured at
baseline and at week 16 during the active phase using euglycemic hyperinsulinemic
clamps. Arterial blood pressure decreased similarly in both groups. Whole body
glucose uptake (M-value) increased with amlodipine from 3.63 +/- 0.32 (mean +/-
SEM) to 3.97 +/- 0.31 mg/kg/min (P = .02). A similar tendency was observed with
enalapril: from 3.59 +/- 0.32 to 3.94 +/- 0.30 mg/kg/min (P = .09). A trend to
lower steady-state insulin level during the second clamp (compared to baseline)
was observed in both groups. The clamp-derived insulin sensitivity index (that
corrects for steady-state insulin levels and glucose levels during the clamp)
increased similarly in both groups: from 1.15 +/- 0.11 to 1.39 +/- 0.13 with
amlodipine (P = .03) and from 1.25 +/- 0.13 to 1.49 +/- 0.16 with enalapril (P =
.01). LDL cholesterol decreased with amlodipine (mean change, -11.3 mg/dL, P =
.004). Amlodipine and enalapril were associated with increments in insulin
sensitivity. Amlodipine provided an additional benefit with decreased low density
lipoprotein cholesterol levels.
PMID- 10192235
TI - Central vasopressin is modulated by chronic blockade of the renin-angiotensin
system in experimental left ventricular hypertrophy.
AB - We studied the interaction of the central renin-angiotensin system (RAS) and
vasopressin system in rats with left ventricular hypertrophy (LVH) due to aortic
banding. In these animals plasma vasopressin is elevated and vasopressin content
is increased in specific brain areas. Chronic blockade of the RAS by angiotensin
converting enzyme (ACE) inhibition (ramipril) and AT1 receptor antagonism
(losartan) significantly attenuated circulating and central vasopressin in rats
with LVH. Given the antidiuretic, vasoconstrictive, and growth-promoting effects,
vasopressin may participate in the cardiovascular alterations in LVH. Blockade of
the RAS strongly ameliorates central and peripheral-vasopressin. Therefore,
central modulatory effects on vasopressin might contribute to the therapeutic
efficacy of ACE inhibitors and AT1 antagonists.
PMID- 10192234
TI - Polymorphisms of the endothelin-A and -B receptor genes in relation to blood
pressure and myocardial infarction: the Etude Cas-Temoins sur l'Infarctus du
Myocarde (ECTIM) Study.
AB - Endothelin-1 is a potent vasoconstrictor that has also mitogenic properties,
stimulating the synthesis and secretion of several vasoactive molecules. There is
much evidence to suggest that endothelin-1 might be involved in the pathogenesis
of hypertension, atherosclerosis, and ischemic heart disease. Endothelin-1 exerts
its effects through at least two receptors, ET(A) and ET(B), which are encoded by
different genes and have separate tissue distributions and biologic properties.
The objective of this study was to identify polymorphisms of the ET(A) and ET(B)
receptor genes and to study their association with myocardial infarction (MI) and
blood pressure. The coding regions and 1.3 kb upstream of the ET(A) and ET(B)
receptor genes were explored by polymerase chain reaction/single strand
conformation polymorphism. Six polymorphisms were found in the ET(A) receptor
gene and three in the ET(B) receptor gene. Most of these polymorphisms were
frequent. Associations between the detected polymorphisms, blood pressure, and MI
were examined in the ECTIM study, a multicenter study comparing 652 patients
having survived an MI and 773 controls from Belfast (Northern Ireland) and
France. Alleles at the different polymorphic sites were similarly distributed in
patients with MI and controls. Allele frequencies were similar in both countries,
except for the ET(A)/-231 G allele, which appeared more frequently in France than
in Belfast (P < .01). The mean systolic and diastolic blood pressure levels did
not significantly differ between genotypes. However, a C/T substitution located
in the nontranslated part of exon 8 of the ET(A) receptor gene (ET(A)/EX8nt1363)
was associated with pulse pressure (P < .005). These results do not support an
involvement of the endothelin receptor genes in a predisposition to MI or the
determination of blood pressure levels, but suggest that a polymorphism of the
ET(A) receptor gene might influence the pulse pressure. This result will have to
be confirmed in other studies.
PMID- 10192236
TI - Abnormalities of membrane function and lipid metabolism in hypertension: a
review.
AB - Hypertension, which is characterized by multiple alterations in the structure and
function of the cell membrane, is often associated with important metabolic
abnormalities including those concerning lipid metabolism. Dyslipidemia
accompanying essential hypertension consists of elevated plasma triglycerides,
low HDL cholesterol, and increased levels of atherogenic LDL cholesterol
particles. The altered membrane microviscosity seen in hypertensive subjects
reflects the changes of membrane lipid composition resulting from intensive
exchange between circulating and membrane lipids, as well as from abnormal
cellular lipid synthesis and metabolism. The changes of membrane microviscosity
are known to modulate the activity of proteins involved in ion transport, signal
transduction, cell Ca2+ handling, intracellular pH regulation, etc. Alterations
in plasma or membrane lipids are indeed closely associated with ion transport
abnormalities as well as with impaired control of cytosolic Ca2+ and pH in
various forms of hypertension in both humans and rats. Such lipid-dependent
modifications of membrane properties in cells participating in the cardiovascular
regulation might be a part of pathogenetic mechanisms responsible for chronic
blood pressure elevation. Thus nutritional and pharmacologic interventions aiming
to normalize abnormal lipid metabolism could be useful for amelioration of
membrane abnormalities and lowering of high blood pressure. Future studies of
functional membrane alterations in hypertension or dyslipidemia will therefore
require the detailed determination of membrane lipid composition and the
measurement of microviscosity in particular membrane domains.
PMID- 10192237
TI - Relationship between vitamin D3 and peripheral circulation in moderate essential
arterial hypertension.
PMID- 10192238
TI - History of women in nephrology (1918 to 1960).
AB - Little has been written concerning the role of women in nephrology in America
during the first half of the twentieth century. However, the records show that
women scientists made substantial contributions to nephrology and definitely were
involved in research efforts at a number of prestigious academic institutions
that had interests focused on kidney function in health and disease. Here, we
describe the contributions of some of these pioneering women scientists to whom
nephrology shall always be indebted.
PMID- 10192239
TI - Improving the environment for women in nephrology.
AB - Data on the representation and distribution of women in nephrology and internal
medicine show why continuing efforts are required to ensure that women reach
their potential in academic medicine. Some of the cumulative disadvantages that
women face in their professional development are summarized, particularly those
related to obtaining mentoring. Efforts on the part of the Association of
American Medical Colleges and one department of medicine are described as
examples of strategic interventions, and other actions are suggested, with the
goal of increasing women's leadership in nephrology, as well as in academic
medicine overall.
PMID- 10192240
TI - The changing face of nephrology.
AB - Projected requirements for nephrology physicians indicate a need for an increase
in the number of nephrology trainees. In addition, government regulations are
creating the climate to diminish the entry of international medical graduates
into all residency programs. To meet the needs of renal patients, especially
those with end-stage renal disease, and such areas of growth as nephrology
research, more US medical graduates, particularly women and members of minority
groups, will have to select nephrology as a career. This article discusses issues
that this challenge raises for the specialty, including the impact on patient
care, mentoring, and the use of nonphysician clinicians.
PMID- 10192241
TI - Gender matters in renal research: a National Institutes of Health perspective.
AB - The National Institutes of Health (NIH) currently anticipates a period of growth
in budgets, making renal community input into research planning and prioritizing
particularly important. In considering which women's health issues should be
given high priority for research study, the questions of both public health
impact and scientific opportunity should be considered. A series of health topics
in which there is some evidence for particular impact on women's health are
briefly reviewed, and the process the NIH uses for community input and priority
setting are discussed.
PMID- 10192242
TI - From the bedside to the boardroom.
AB - There is a need for physicians, including women physicians, to pursue medical
management careers within our health care institutions. The physician's training
provides skills that are important and transferable to management. These skills
are discussed. However, there are gaps in our training related to population
approaches, personnel management, and finances that must be learned. Success in a
management career is highly dependent on building a high-functioning, integrated
team, and the approach to this is discussed.
PMID- 10192243
TI - Osteoporosis in end-state renal disease.
AB - Maintaining the intricate bone mineral homeostasis in patients with chronic renal
failure and renal osteodystrophy is a complex and challenging process. In
addition to the well described high-turnover bone disease caused by secondary
hyperparathyroidism and low-turnover disease in the form of osteomalacia (either
from aluminum or a dynamic bone disease) osteopenia also is present in end-stage
renal disease patients. In contrast to abnormalities in the ability of bone to
remodel, osteopenia is a deficiency in bone mass or volume. The prevalence of
fractures in dialysis patients, regardless of histomorphometry appears to exceed
that observed in elderly women. This osteopenia that occurs in chronic renal
failure patients secondary to multiple factors that include hypogonadism,
medications (such as corticosteroids), immobilization, and the typical osteopenia
associated with aging. All of these factors amplify the risk of fracture in
dialysis patients.
PMID- 10192244
TI - Pathophysiology and clinical management of polycystic kidney disease in women.
AB - Women of all geographic, racial, and ethnic groups are afflicted by autosomal
dominant polycystic kidney disease (ADPKD), which is the most common, lethal
genetic disease that is inherited as a dominant trait. General issues concerning
epidemiology, diagnostic testing, clinical management of pain, hypertension, and
intracranial aneurysms are discussed, as well as a short overview of our current
understanding of the pathophysiological features, including some new molecular
insights. Specific issues affecting the care of women are also discussed,
including the management of liver cysts and fertility and pregnancy in ADPKD.
PMID- 10192245
TI - Glomerular filtration rate in normal and abnormal pregnancies.
AB - During normal pregnancy, an early, marked, and sustained increase occurs in
glomerular filtration rate (GFR) secondary to renal vasodilation. An optimal
increase in GFR is a good predictor of pregnancy outcome. The pregnant rat
provides an excellent model of the gestational renal hemodynamic response, and
invasive studies in this species have extended our understanding of the
glomerular hemodynamic mechanisms involved. Of note, the chronic renal
vasodilation of pregnancy is not associated with glomerular hypertension, and
pregnancy has no long-term injurious effects when kidney function is normal. The
renal vasodilatory response to pregnancy is robust and persists in a range of
mild renal diseases and in renal transplant recipients. When maternal renal
function is moderately or severely compromised, however, the renal responses
during pregnancy are often attenuated, and pregnancy may also accelerate the
course of the renal disease. Studies in the rat have indicated a wide range of
possible renal hemodynamic responses to pregnancy in rats with underlying kidney
damage, which seem to be disease specific. Irrespective of the renal vascular
response to pregnancy, there is no evidence to date suggesting that pregnancy
leads to glomerular hypertension.
PMID- 10192247
TI - Renin-angiotensin genes in renal development and the occurrence and progression
of renal diseases.
AB - The function of angiotensin II has evolved from recognition of its
vasoconstrictive functions and regulations of fluid balance to its pivotal role
in progressive tissue destruction, particularly renal scarring. This review
highlights angiotensin's newest role in normal and abnormal organogenesis as well
as the impact on renal damage of subtle variations in genes that control
angiotensin's actions including angiotensinogen, angiotensin converting enzyme,
and its receptors.
PMID- 10192246
TI - Principles of dialysis: special issues in women.
AB - Nephrologists are frequently responsible for the primary care of their female
patients. As such, they must be aware of medical issues that are unique to women.
Although many of the medical considerations are similar to those in women without
renal disease, there are a number of special considerations unique to end-stage
renal disease (ESRD) patients. Women comprise a smaller proportion of the
dialysis population and have better survival rates than men do. The improved
survival is less marked than seen in the general population and may be function
of differential susceptibility to disease processes, socio-cultural factors, or
gender differences in acceptance or transplantation rates. A variety of factors
are important in choosing dialysis modality including lifestyle issues and
previous abdominal surgery. Women with ESRD are at high risk of both sexual and
gonadal dysfunction, for which the latter may be treated with replacement
hormones. Pregnancy is rare and requires an increase in the dose of dialysis and
the care of a team of experienced physicians. Finally, awareness and
implementation of routine health maintenance recommendations is essential in the
care of female dialysis patients.
PMID- 10192248
TI - Regulation of potassium transport in the maturing kidney.
AB - Kidneys of full-term newborn humans and animals conserve potassium (K+), a
condition essential for growth. The cortical collecting duct (CCD) is uniquely
adapted to accomplish this task early in life. CCDs isolated from newborn rabbits
and microperfused in vitro show no net K+ secretion until after the third week of
life; in contrast, segments isolated from adult animals secrete net K+ at high
rates. The magnitude and direction of net K+ transport in the CCD reflect the
balance of opposing fluxes of K+ secretion and K+ absorption mediated by
principal and intercalated cells, respectively. The absence of net K+ secretion
in the CCD early in life may thus be caused by a limited capacity of principal
cells for K+ secretion and/or an excess of K+ absorption by intercalated cells.
Recent studies provide data to support both possibilities. Patch-clamp analysis
detects few conducting apical K+-secretory channels in neonatal principal cells,
whereas fluorescent functional assays identify significant activity of the apical
hydrogen, potassium adenosine triphosphatase (H+,K+-ATPase), a pump that
reabsorbs K+ in exchange for H+s, in adjacent intercalated cells. Under
conditions prevailing in vivo, the sum of the fluxes mediated by these two cell
types likely contributes to the relative K+ retention characteristic of the
neonatal kidney.
PMID- 10192249
TI - Treatment of mesangial immunoglobulin A glomerulonephritis.
AB - Mesangial immunoglobulin A glomerulonephritis does not progress unless
microscopic hematuria presents at levels over 100,000/mL, proteinuria presents at
levels over 0.5 g in 24 hours, or hypertension is inadequately controlled.
Hypertension, microscopic hematuria, and proteinuria all can be controlled; the
evidence for control of these three risk factors is reviewed. The evidence for
prevention of progression in mesangial immunoglobulin A glomerulonephritis is
also reviewed.
PMID- 10192250
TI - Lupus nephritis: update on pathogenesis and disease mechanisms.
AB - Immune-mediated nephritis is a common complication of systemic lupus
erythematosus (SLE). It is now clear that multiple and independent mechanisms
contribute to disease onset and pathogenesis, which may explain the remarkable
phenotypic and histopathological heterogeneity observed in human SLE.
Identification and characterization of disease-relevant autoantibodies, cellular
effectors, and soluble immune elements have provided crucial insight into the
immunologic interactions that promote renal immune injury. It is now clear that
nephritogenic autoantibodies of diverse specificity localize to the kidney by a
variety of mechanisms. They are accompanied by activated macrophages and T cells
recruited in part through enhanced and abnormal production of macrophage growth
factors and cytokines. These pathways provide novel targets for therapeutic
intervention to prevent or ameliorate the aggressive autoimmune nephritis that
characterizes SLE.
PMID- 10192251
TI - Cellular immunity and the tubulointerstitium.
AB - In the past two decades, there has been an increasing appreciation of the
relationship between alterations in the interstitial compartment of the kidney
and decrements in glomerular filtration rate. In human renal disease, injury
patterns in the interstitial compartment consist of a spectrum from predominantly
inflammatory to predominantly fibrotic. This review synthesizes information on
the pathogenesis of inflammatory interstitial nephritis into a conceptual
framework for understanding this important form of human renal disease.
PMID- 10192252
TI - Experimental studies in distal urinary acidification: bringing the bedside to the
bench.
AB - The renal tubular acidosis syndromes are nonuremic defects of urinary
acidification. They are characterized by a normal anion gap and hyperchloremic
metabolic acidosis; plasma potassium may be normal, low, or high, depending on
the syndrome present. As new technologies have been applied to biology, we now
better understand the basic lesions of these important syndromes.
PMID- 10192253
TI - Citrate transport by the kidney and intestine.
AB - Citrate is an important metabolite that is transported in the kidney and
intestine. Low urinary citrate concentrations, which may be determined in part by
transport processes in the kidney, are associated with the development of kidney
stones. Citrate is reabsorbed from the tubular filtrate in the renal proximal
tubule on a sodium-coupled transporter, the Na+/dicarboxylate cotransporter, with
a broad substrate specificity for Krebs cycle intermediates. The same transporter
is found on the brush-border membrane of enterocytes. In contrast to the well
characterized apical pathway for citrate, there is relatively little information
about citrate transport across the basolateral membrane. Recently, the
complementary DNAs coding for the Na+/citrate transporters from the apical
membranes of rabbit and human kidney, NaDC-1 and hNaDC-1, have been cloned and
sequenced. These transporters belong to a separate gene family that includes the
renal Na+/sulfate cotransporter, NaSi-1.
PMID- 10192254
TI - Cardiorenal destiny: the role of genes and environmental factors.
AB - For many years, it has been known that genes and environmental factors interact
to determine an individual's blood pressure. The purpose of this article is
twofold. First, the authors review current molecular genetic approaches to
delineating genes that lead to the development of hypertension, focussing on the
renin-angiotensin system. We then consider perinatal environmental factors that
impact adult blood pressure. Epidemiologic data suggest that good maternal
nutritional status is essential to avoid programming individuals for future
health problems as adults. One factor that appears to play an important role in
programming for hypertension in adulthood is maternal dietary protein restriction
during pregnancy, possibly by suppression of the fetal renin-angiotensin system
and consequent impairment of renal development. The association between lower
birthweight and increased adult blood pressure, established in epidemiologic
studies, may be caused by suboptimal maternal diet or placental insufficiency,
resulting in transient changes in fetal hormone systems or gene expression that
permanently alter the structure and function of the kidney and vasculature.
PMID- 10192255
TI - Women in nephrology: shaping our future.
PMID- 10192256
TI - Osteotomy and osteoarthritis.
PMID- 10192257
TI - Stem cell research.
PMID- 10192258
TI - Overuse tendinitis.
PMID- 10192259
TI - Intermediate-term clinical and radiographic results of Synatomic and AGC knee
prostheses.
AB - This study compared two total knee prostheses to determine whether the clinical
and radiographic outcomes were different, focusing primarily on the
patellofemoral articulation. The study group was comprised of 75 Synatomic (short
stemmed, anatomic VF type) and 79 AGC 2000 (universal, nonanatomic) prostheses.
Patients underwent follow-up for an average of 63 and 50 months, respectively. At
latest follow-up, the mean knee joint score was 84.4 in the Synatomic and 86.5 in
the AGC group. Mean knee function scores were 63.5 and 63.4, respectively. No
statistically significant difference was noted between the two prostheses.
PMID- 10192260
TI - The effect of varus tilt on contact stresses in total knee arthroplasty: a
biomechanical study.
AB - The contact stress produced in the tibiofemoral joint from a varus-tilted tibial
component was tested in five total knee prostheses. Peak and mean stresses were
measured with a digital electronic sensor under compressive load at 15 degrees
and 90 degrees flexion. Stresses were measured with the tibial component tilted 0
degrees and 5 degrees in the mediolateral direction. At a 5 degree tilt, the
Advantim, the Miller-Galante II, and the Omnifit prostheses, which have a flat
configuration on the femoral and tibial surfaces in the coronal plane, had
significantly greater stresses than the LCS and the Profix prostheses, which have
tibial and femoral components with matching curved surfaces in the coronal plane.
These results suggest that the femoral component surface should have a radius of
curvature that matches that of the tibial articular surface in the coronal plane
to achieve a large contact area even in varus-valgus tilting.
PMID- 10192261
TI - Head and neck replacement prostheses in revision hip arthroplasty: experience
with a single modern design.
AB - This study reviewed 52 revision hip arthroplasties in which calcar cortical
deficiencies were addressed by implantation of a cemented, modern-design head and
neck replacement femoral prosthesis. Mean clinical follow-up was 38 months.
Radiographic follow-up beyond 22 months was available for 34 patients (mean: 35.8
months). Mean Mayo clinical hip score (maximum: 80) improved from 28.2
preoperatively to 55.2 at last follow-up. No femoral component was revised for
aseptic loosening. However, radiographic analysis demonstrated one prosthesis was
probably loose and two were possibly loose. A 92.7% Kaplan-Meier 5-year implant
survival rate free from radiographic loosening was projected. This type of
prosthesis has yielded good clinical results and excellent early survival.
PMID- 10192262
TI - Magnetic resonance imaging evaluation of thecal sac diameters following
laminectomy in the lumbar spine.
AB - Sagittal magnetic resonance images (MRIs) from 20 patients who had postoperative
persistent or recurrent low back pain were reviewed to study the thecal sac
diameter at laminectomy sites. The thecal sac anteroposterior diameter was
measured in three sites: the maximum AP diameter at the laminectomy site, and the
proximal and distal levels to the laminectomy site. A comparison between the
thecal sac AP diameter at laminectomy sites and the average diameter of both the
proximal and distal levels was then made. Based on the measurements, the
diameters of the thecal sac were divided into three groups. Patients in group A
(5 cases) had a constriction (the thecal sac AP diameter at the laminectomy site
was less than the average diameter of both the proximal and distal levels) of the
thecal sac at the laminectomy site. Patients in group B (12 cases) had an
expansion (the thecal sac AP diameter at the laminectomy site was more than the
average diameter of both the proximal and distal levels) of the thecal sac.
Patients in group C (3 cases) demonstrated no change. This study suggests that
there was no correlation between the thecal sac AP diameter at laminectomy site
and postoperative low back pain.
PMID- 10192263
TI - The treatment of symptomatic os acromiale.
AB - Os acromiale is an uncommon condition of the shoulder. When symptomatic, os
acromiale may cause impingement pain, rotator cuff tears, or pain through
abnormal motion at the unfused apophysis. Treatment of symptomatic os acromiale
is controversial. This article reports on four patients with symptomatic meso
acromions who were treated with open reduction and internal fixation. All four
patients recovered full function postoperatively with UCLA shoulder rating scores
improving from 19 preoperatively to 35 postoperatively. Open reduction and
internal fixation of a symptomatic meso-acromion is a reliable and reproducible
technique in which the deltoid attachment and lever arm are minimally affected.
PMID- 10192264
TI - Management of hallux amputation.
PMID- 10192265
TI - Chondroblastoma-like osteosarcoma.
PMID- 10192266
TI - Adhesive capsulitis of the hip.
PMID- 10192267
TI - Incomplete rupture of the inferior patellar ligament after total knee
arthroplasty caused by a loose patellar component.
PMID- 10192268
TI - Aggressive wear-debris pseudotumor following total hip replacement.
PMID- 10192269
TI - Neurilemoma originating from a deep branch of the ulnar nerve.
PMID- 10192270
TI - Radiologic case study. Fractures of the foot masquerading as ankle injuries.
AB - An ankle radiographic series frequently is obtained when a patient presents with
an acute ankle and foot injury. Although many fractures are confined to the ankle
and are readily apparent, fractures of the foot can mimic ankle injuries. It is
important to differentiate these fractures of the foot from the more common ankle
sprain. Most ankle sprains are treated with ice, compression, and elevation,
followed by range-of-motion exercises and progressive weight bearing as
tolerated. When foot fractures are not identified, however, lack of appropriate
treatment can result in late complications. Concentration on key areas as
described here will reduce the incidence of missed fractures of the foot in these
patients.
PMID- 10192271
TI - Prenatal substance exposure: effects on attention and impulsivity of 6-year-olds.
AB - Attention and impulsivity of prenatally substance-exposed 6 year olds were
assessed as part of a longitudinal study. Most of the women were light to
moderate users of alcohol and marijuana who decreased their use after the first
trimester of pregnancy. Tobacco was used by a majority of women and did not
change during pregnancy. The women, recruited from a prenatal clinic, were of
lower socio-economic status, and over half were African American. Attention and
impulsivity were assessed using a Continuous Performance Task. Second and third
trimester tobacco exposure and first trimester cocaine use predicted increased
omission errors. Second trimester marijuana use predicted more commission errors
and fewer omission errors. There were no significant effects of prenatal alcohol
exposure. Lower Stanford-Binet Intelligence Scale composite scores, male gender,
and an adult male in the household also predicted more errors of commission.
Lower SBIS composite scores, younger child age, maternal work/ school status, and
higher maternal hostility scores predicted more omission errors. These findings
indicate that prenatal substance use has an effect on attentional processes.
PMID- 10192272
TI - Developmental effects of phenytoin may differ depending on sex of offspring.
AB - Phenytoin (sodium salt), a developmental neurotoxicant, was administered orally
by gavage (50-150 mg/kg) to pregnant rats on days 7-18 of gestation. Various
developmental and behavioral indices were evaluated. Results indicated that
phenytoin produced decreases in maternal and pup body weight gains, pup
hindbrain, and F1 adult forebrain, whole brain, and cerebellar weights.
Behavioral/developmental effects included performance deficits in a modified
Morris water maze assay, in air righting and auditory startle responses, and
increases in locomotor activity, accelerated eye opening, incisor eruption,
negative geotaxis, and olfactory orientation. Female offspring appeared to be
more severely affected when measuring incisor eruption, negative geotaxis, air
righting, reactivity, and locomotor and maze activity. Males appeared to be more
affected when measuring eye opening, olfactory orientation, and decreases in
startle response. This study suggests that prenatal phenytoin exposure may result
in developmental changes and behavioral deficits that may differ depending on the
sex of the offspring.
PMID- 10192273
TI - Timing: A critical determinant of the functional consequences of neonatal 6-OHDA
lesions.
AB - Previous data have indicated that intrastriatal (IS) lesions of the dopamine (DA)
system early in development result in a selective effect on D1 receptor
expression and sensitivity, which is not seen with adult lesions or lesions made
later in development. The purpose of the present study was to test the hypothesis
that the timing of the lesion is a critical determinant of the consequences of DA
depletion during development. Rats received IS injections of 6-hydroxydopamine (6
OHDA) on day of birth/postnatal day 1 (P0/1) or P7, which resulted in similar
decreases in the number of DA uptake sites (> or =70% loss), a measure of DA
terminal density. As adults, lesioned rats were challenged with DA receptor
agonists to examine the functional sensitivity of D1 and D2 receptors. In
adulthood, P0/1-lesioned rats exhibited increases in oral dyskinesias and rearing
behavior following treatment with the partial D1 receptor agonists, SKF38393 and
SKF77434, whereas rats lesioned on P7 exhibited increases in grooming. P7
lesioned rats also exhibited increases in gnawing, explosive jumping, and self
biting behavior following treatment with the full D1 receptor agonist SKF82958,
which were not observed in the other groups. The results support the hypothesis
that the timing of DA denervation is of paramount importance for governing the
functional consequences of neonatal lesions, as measured by the incidence of DA
agonist-induced behaviors in adulthood.
PMID- 10192274
TI - Postnatal effects of retinoic acid on cerebellar development.
AB - Retinoic acid(RA) is a potent teratogen to which the early CNS is known to be
highly sensitive. However, very little is know about the postnatal effects of RA.
The cerebellum is a candidate for postnatal RA toxicity, as it develops late and
exhibits temporal patterns of RA synthesis that are synchronized with
developmental stages. Northern blotting shows that the cerebellum expresses
receptors for RA, predominantly of the RXR group activated by 9-cis RA. To
determine whether development can be disrupted by RA excess, newborn rats were
injected with RA at a time when endogenous RA levels are normally low.
Histological examinations at postnatal day 14 revealed loss of a subpopulation of
proliferating granule cells, and adult cerebella showed clusters of ectopic
granule cells located in the molecular layer. Thus, although the granule cells
may normally be regulated by endogenous RA, they are sensitive to abnormally high
RA concentrations.
PMID- 10192275
TI - Behavioral effects following single and combined maternal exposure to PCB 77
(3,4,3',4'-tetrachlorobiphenyl) and PCB 47 (2,4,2',4'-tetrachlorobiphenyl) in
rats.
AB - The present study has compared the neurobehavioral effects of two structurally
different PCB congeners or their combination in rats. Time-mated Long-Evans rats
received daily injections of the coplanar PCB 77 (3,4 3',4'-TCB: 0.5 or 1.5
mg/kg), the di-ortho-chlorinated PCB 47 (2,4,2',4'-TCB: 1.5 mg/kg) or a congener
mixture (0.5 mg/kg PCB 77 + 1.0 mg/kg PCB 47) from day 7 to 18 of gestation. The
PCB exposure levels in brain and perirenal fat of dams and offspring were
determined by GC/ECD on gestational day 19 (GD 19), postnatal day 21 (PND 21),
and PND 45. PCB 77 was accumulated to a smaller degree than PCB 47. On GD 19, PCB
77 was found to a greater extent in the brains of the offspring than in the
brains of the dams, whereas the level of PCB 47 was almost the same in dams and
offspring. The testing of open-field behavior in male rats on PND 18 and PND 70
revealed an altered distribution of activity with enhanced activity in the inner
zone in PCB 77-treated rats compared to all other groups, while the overall
activity was not changed. Distance traveled and rearing behavior on PND 340 were
elevated relative to controls in all PCB-treated groups, indicating age-related
effects of maternal exposure. A step-down passive avoidance task revealed
decreased latencies in the PCB 77 and combined exposure groups on PND 80. Only
PCB 77-treated animals showed increased latencies on PND 100 on the haloperidol
induced catalepsy test. These results indicate long-term effects of maternal
exposure to PCB 77 on emotional and motor functions. At the dose levels used in
the present experiments, the two congeners given in combination did not cause
additive or synergistic effects. Instead, concurrent exposure to PCB 47 seemed to
counteract PCB 77-induced changes in the pattern of activity.
PMID- 10192276
TI - The effect of diazepam and promethazine treatment during pregnancy on the somatic
development of human offspring.
AB - The postnatal longitudinal somatic, neurological, mental, and behavioral
developments were studied in children at birth, 8, 15, and 24 months of life,
whose mothers were treated during pregnancy with clinical doses of diazepam (n =
126) and promethazine (n = 127) and whose mothers were unexposed. The latter
group was differentiated in negative (n = 256) and positive (n = 102) control
children. The positive control group involved mothers who had pregnancy
complications similar to those of mothers in the drug groups but who were not
treated with CNS-active drugs during pregnancy. It is very difficult to recruit
persons for the study and control groups who are appropriate for comparative
evaluation. Only firstborns and the so-called "normal" newborn infants were
studied; children with low birth weight, major abnormalities, severe neonatal
diseases, etc., were excluded. In this article the study design, study materials,
and somatic (weight, length, head circumference) development are described. At
birth, children had a lower weight in the diazepam group, but it was not noted at
the eighth month of postnatal life.
PMID- 10192277
TI - MPTP-induced Parkinsonism in minipigs: A behavioral, biochemical, and
histological study.
AB - Fourteen male Gottingen minipigs were used in this study. Nine were administered
N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) at a dosage of 1 mg/kg/day,
SC, for 6 days, the last five pigs received saline injections for 6 days. All
MPTP-treated animals developed Parkinson symptoms, i.e., muscle rigidity,
hypokinesia, and impaired coordination within 5 days. The brain levels of
dopamine (DA), and its major metabolites dihydroxyphenylacetic acid (DOPAC) and
homovanillic acid (HVA), were determined in caudatum and putamen 2, 14, and 93
days (n = 3/time point) after the last drug administration. In eight of the MPTP
treated animals, striatal DA, DOPAC, and HVA concentrations were reduced from 50
to 95% compared to control animals at all time intervals. Animals with the lowest
striatal DA concentrations showed the most severe signs of Parkinsonism. The
number of cells in substantia nigra (SN) showed a decline only 3 months after
MPTP treatment. The minipigs represent a nonprimate model of MPTP-induced
parkinsonism syndromes lasting at least months.
PMID- 10192278
TI - Bolus maternal cocaine administration does not produce a large increase in fetal
sheep cerebral cortical glutamate concentration.
AB - Human cocaine use during pregnancy may result in postnatal neurologic dysfunction
and abnormal behavior. L-Glutamate, the major excitatory neurotransmitter in the
brain, plays an important role in cerebral cortical development. An optimal level
of glutamate is required for normal neuronal development. We tested whether acute
cocaine exposure produces large increases in glutamate release in the intact
cerebral cortex of the near-term fetal sheep. Cocaine 3.0 mg kg(-1) IV bolus
produced the expected increase in maternal and fetal mean arterial pressure,
increase in fetal heart rate, decrease in uterine blood flow, and decrease in
fetal arterial blood pO2 (N = 5). The percentage increases in extracellular
glutamate concentration in the fetal cerebral cortex measured by in utero
microdialysis were 7%, 15%, 17%, 17%, and 43% in each fetus (upper 95% confidence
bound for the median = 43%). We conclude that if cocaine increases glutamate
concentration in the developing cerebral cortex, the increase in magnitude is
small relative to the changes produced by other interventions such as ethanol or
umbilical cord occlusion. Mechanisms other than increases in cerebral cortical
glutamate concentration probably contribute to the neurologic injury associated
with prenatal cocaine exposure.
PMID- 10192279
TI - Temperature dependence and independence of effects of pentobarbital on visual
evoked potentials of rats.
AB - Visual cortex flash evoked potentials (FEPs), pattern reversal evoked potentials
(PREPs), and body temperature were measured in hooded rats following IP
injections on separate days of saline, and of 15 and 30 mg pentobarbital/kg body
weight. Two experiments were performed, differentiated by standard (23 degrees C)
and warm (31 degrees C) room temperatures. The 30 mg/kg dose produced hypothermia
of 2.6 degrees C in the standard environment, but not in the warm environment.
Early components of FEPs were generally increased in amplitude by the 15 mg/kg
dose, and decreased by the 30 mg/kg dose at 23 degrees C. At 31 degrees C, the 30
mg/kg dose did not decrease early component amplitude, suggesting that
hypothermia can potentiate some effects of pentobarbital. Amplitudes of late FEP
components were depressed at both ambient temperatures. The main PREP components
N1P1 and P1N3 were increased in amplitude by the 15 mg/kg dose, but returned to
near baseline levels at 30 mg/kg, at both temperatures. PREP component N2P2 was
reduced in amplitude by the 30 mg/kg dose only at 23 degrees C. Treatment with 30
mg/kg pentobarbital increased FEP and PREP latencies at both ambient
temperatures, but the magnitudes of the increases at 31 degrees C were typically
less than half those observed at 23 degrees C. These results indicate that
hypothermia contributes to some pentobarbital-induced changes in both FEPs and
PREPs, but that pentobarbital also produces effects independent of hypothermia.
PMID- 10192280
TI - Effect of late fetal irradiation on adult behavior of mouse: Dose-response
relationship.
AB - Pregnant Swiss mice were exposed to 0.3-1.5 Gy of gamma radiation on day 17 of
gestation and allowed to deliver the offspring. When the F1 mice were 6 months
old, they were subjected to a number of behavioral tests. Open-field and dark
bright arena tests were conducted to study locomotor and exploratory activities.
Learning and memory were tested by holeboard activity, conditioned avoidance
response, and radial arm maze performance. After all the tests, 20 animals (10
males and 10 females) from each group were killed, and their brain weight was
taken. The open-field and dark-bright arena tests showed a significant dose
dependent decrease in the locomotor and exploratory activities. Reduction in time
spent in the dark area and higher locomotor activity in the bright area indicated
a reduced aversion to bright light. But the emotional activities like rearing and
grooming did not change. The learning and memory functions also showed a
significant impairment, even at 0.3 Gy. The deficit in the performance in the
holeboard test, conditioned avoidance response, as well as maze-learning
efficiency, decreased linearly with increase in radiation dose. The brain weight
showed a linear dose-dependent decrease. But the brain/body weight ratio was not
significantly affected even at 1.5 Gy. These results demonstrate that exposure of
a mouse on day 17 of gestation to radiation doses below 1.0 Gy can induce
significant impairment in the adult brain function, without producing any notable
effects on brain morphology. This study also suggests that the retardation of
higher brain function by exposures during the late fetal period may have a
threshold of around 0.3 Gy.
PMID- 10192281
TI - Enhanced responsiveness of the myocardial beta-adrenoceptor-adenylate cyclase
system in the perfused rat heart (I).
AB - Crude myocardial sarcolemmal membrane fractions were prepared from rat hearts
subjected to total global ischemia with and without normoxic reperfusion, or
global anoxic (N2) perfusion with and without normoxic reperfusion. The direct
effects on beta-adrenoceptor number, G-protein levels and stimulation of the
adenylate cyclase (AC) complex were assessed. In terms of AC activation, ischemia
led to a marked increase (4-fold) in sensitivity to terbutaline (beta2-agonist)
and phorbol ester (tetradecanoyl phorbol acetate = TPA) stimulation, whereas the
dobutamine (beta1) responsiveness and Gpp(NH)p activation through
G(s)alpha/G(i2)alpha remained unaltered. However, forskolin-elicited holoenzyme
activity fell markedly during normoxic reperfusion. Ischemia did not change the
beta1-adrenoceptor number, while beta2-receptor population increased by
approximately 45%. Western blots of myocardial G(s)A and G(i2)alpha contents
revealed that ischemia selectively diminished G(i2)alpha levels only by some 50
70%. Contrastingly, anoxia selectively increased the AC sensitivity (2-fold) to
beta1-adrenergic stimulation. As subsequent to ischemia, anoxia also increased
the sensitivity to TPA stimulation, however, only 2-fold. Gpp(NH)p activation was
unchanged, while forskolin-enhanced activity gradually declined, also during
ensuing normoxic reperfusion. Anoxia brought about a 75% enhancement in beta1
receptor number, while beta2-receptors remained unaffected. However, altered
receptor number normalized on termination of normoxic reperfusion. Finally,
anoxia led to a 50-60% decimation of myocardial G(i2)alpha levels, while
G(s)alpha was only marginally reduced. Despite the fact that the ischemia and
anoxia effectuated a similar deterioration of physiological heart parameters,
myocardial contents of energy rich phosphate moieties and loss of G(i2)alpha,
ischemia rendered the most profound increase in responsiveness of the sarcolemmal
AC system.
PMID- 10192282
TI - Structural study of the interaction between the mitochondrial presequence of
cytochrome c oxidase subunit IV and model membranes.
AB - The structural effect of the presequence of cytochrome oxidase subunit IV (p25)
on multilamellar liposomes with different lipid compositions has been
investigated using X-ray diffraction and electron microscopy. The presequence
causes the disordering of the liposomes containing negatively charged lipids,
without destabilizing the bilayer structure or destroying the multilamellar
nature of the liposomes. In the systems containing only zwitterionic lipids, a
small increase in the d-spacing (lamellar stacking spacing) is observed without
any disorder effect suggesting a weaker interaction of the peptide and lipid.
Circular Dichroism measurements of the peptide, in the presence and absence of
the different lipid systems studied, show that the secondary structure of the
peptide is modulated by the lipid environment. Considerable amounts of alpha
helix in the presequence is only observed in the systems containing negatively
charged lipids. These are the same systems for which the disordering effect is
observed with X-ray diffraction. It is proposed that p25 disorders the bilayer
stacking by corrugating the membranes. The results are discussed in terms of the
relevance of the specific lipid properties (e.g., electric charge and ability to
form inverted phases) in determining how the peptide interacts with the lipid and
affects its structural organization. It is suggested that the lipid properties
relevant for the disordering effect induced by the peptide are the same as those
involved in the formation of contact sites between mitochondrial membranes during
the import of nuclear coded proteins.
PMID- 10192283
TI - Further studies on Zn2+ -mediated domain-domain communication in human
erythrocyte band 3.
AB - Human erythrocyte band 3 is purified and reconstituted into vesicles, forming
right-side-out proteoliposomes. Zn2+ entrapped inside the proteoliposomes
inhibits the anion transport activity of band 3, and removal of the cytoplasmic
domain of band 3 is able to diminish Zn2+ inhibition. Thus, the inhibition of
activity of band 3 results from the Zn2+ induced conformational change of the
cytoplasmic domain, which in turn is transmitted to the membrane domain. The
results of intrinsic fluorescence and its quenching by HB and the 35Cl NMR study
indicate that the cytoplasmic domain is essential for the conformational change
induced by Zn2+. SH-blocking reagents, CH(3)I and GSSG, are used to modify the
cytoplasmic domain, where they specifically bind to Cys201 and Cys317. It is
observed that the Zn2+ induced inhibition of anion transport activity is blocked.
This demonstrates that Cys201 and Cys317 are required in Zn2+ -mediated domain
domain communication.
PMID- 10192284
TI - Site-directed selection of oligonucleotide antagonists by competitive elution.
AB - Oligonucleotide ligands that bind a protein or a small molecule of interest are
readily isolated by in vitro selection and amplification of rare sequences from
combinatorial libraries of sequence-randomized oligonucleotides (Gold et al.,
1995). Classic systematic evolution of ligands by exponential enrichment (SELEX)
protocols are affinity based (Tuerk and Gold, 1990), but because many problems
and applications require antagonists, protocols for selecting inhibitors are both
desirable and valuable. A widely applicable approach for isolating inhibitors is
competitive elution with a molecule that binds the targeted molecule's active or
binding site. We have used this approach to isolate antagonists of wheat germ
agglutinin (WGA) from a library of 2'NH2-pyrimidine, 2'OH-purine oligonucleotides
by elution with N N' N"-triacetylchitotriose, (GlcNAc)3. The highest affinity
aptamers have equilibrium dissociation constants of 1 nM-20 nM for WGA, a 10(3)
10(4)-fold improvement relative to (GlcNAc)3, and unlike the carbohydrate, are
highly specific. In addition to competing for binding with (GlcNAc)3, aptamers
inhibit WGA-mediated agglutination of sheep erythrocytes, demonstrating that they
are able to compete with natural ligands presented on the surfaces of cells.
These results illustrate the feasibility of isolating high-affinity, high
specificity antagonists by competitive elution with low molecular weight,
relatively low-affinity, and low-specificity small molecules.
PMID- 10192285
TI - Differential effects of cyclopolyamines on the stability and conformation of
triplex DNA.
AB - Linear polyamines are excellent promoters of triplex DNA formation. The effects
of structural rigidization of polyamines on triplex DNA stability are not known
at present. We wished to develop a series of polyamine analogs as secondary
ligands for triplex DNA stabilization for antigene applications. To accomplish
this goal, we synthesized cyclopolyamines by interconnecting the two amino or
imino groups of linear polyamines with a --(CH2)n-bridge (n=3,4,5). Melting
temperature (Tm) data showed that [4,3]-spermine and [4,4]-spermine stabilized
poly(dA) x 2poly(dT) triplex at >25 microM concentrations (Tm = 71 degrees C at
100 microM). The dTm/dlog [polyamine] values for these compounds were 26 and 40,
respectively. [4,3]-Spermine and [4,4]-spermine also stabilized triplex DNA
formed by a purine-motif triplex-forming oligonucleotide, TG3TG4TG4TG3T with its
target duplex, as determined by Tm, circular dichroism (CD) spectroscopy, and
electrophoretic mobility shift assay (EMSA). In contrast, [4,4]-putrescine and
[4,5]-putrescine as well as [4,5]-spermine had no triplex DNA stabilizing effect.
CD spectra also showed triplex DNA aggregation and psi-DNA formation at >100
microM [4,3]-spermine. These data demonstrate that structural rigidization of
linear polyamines has a profound effect on their ability to stabilize triplex DNA
and provoke conformational transitions.
PMID- 10192286
TI - Length variation of helix III in a hammerhead ribozyme and its influence on
cleavage activity.
AB - The previously described HIV-1 directed hammerhead ribozyme 2as-Rz12 can form
with its target RNA 2s helices I and III of 128 and 278 base pairs (bp). A series
of derivatives was made in which helix III was truncated to 8, 5, 4, 3, and 2
nucleotides (nt). These asymmetric hammerhead ribozymes were tested for in vitro
cleavage and for inhibition of HIV-1 replication in human cells. Truncation of
helix III to 8 bp did not affect the in vitro cleavage potential of the parental
catalytic antisense RNA 2as-Rz12. Further truncation of helix III led to
decreased cleavage rates, with no measurable cleavage activity for the 2 bp
construct. All catalytically active constructs showed complex cleavage kinetics.
Three kinetic subpopulations of ribozyme-substrate complexes could be
discriminated that were cleaved with fast or slow rates or not at all. Gel
purification of preformed ribozyme-substrate complexes led to a significant
increase in cleavage rates. However, the complex cleavage pattern remained. In
mammalian cells, the helix III-truncated constructs showed the same but no
increased inhibitory effect of the comparable antisense RNA on HIV-1 replication.
PMID- 10192287
TI - The antisense sequence of the HIV-1 TAR stem-loop structure covalently linked to
the hairpin ribozyme enhances its catalytic activity against two artificial
substrates.
AB - This work is an in vitro study of the efficiency of catalytic antisense RNAs
whose catalytic domain is the wild-type sequence of the hairpin ribozyme, derived
from the minus strand of the tobacco ringspot virus satellite RNA. The sequence
in the target RNA recognized by the antisense molecule was the stem-loop
structure of the human immunodeficiency virus-1 (HIV-1) TAR region. This region
was able to form a complex with its antisense RNA with a binding rate of 2 x
10(4) M(-1)s(-1). Any deletion of the antisense RNA comprising nucleotides of the
stem-loop resulted in a decrease in binding rate. Sequences 3' of the stem in the
sense RNA also contributed to binding. This stem-loop TAR-antisense segment,
covalently linked to a hairpin ribozyme, enhanced its catalytic activity. The
highest cleavage rate was obtained when the stem-loop structure was present in
both ribozyme and substrate RNAs and they were complementary. Similarly, an
extension at the 5'-end of the hairpin ribozyme increased the cleavage rate when
its complementary sequence was present in the substrate. Inclusion of the stem
loop at the 3'-end and the extension at the 5'-end of the hairpin ribozyme
abolished the positive effect of both antisense units independently. These
results may help in the design of hairpin ribozymes for gene silencing.
PMID- 10192288
TI - Effective treatment of murine leukemia with antisense poly-2'O-(2,4
dinitrophenyl)-oligoribonucleotides.
AB - Two antisense poly-2'-O-(2,4-dinitrophenyl)-oligoribonucleotides (poly-DNP-RNA)
have been synthesized and tested for the treatment of murine leukemia. Compound I
was designed as a bifunctional inhibitor of either the reverse transcriptase (RT)
activity or viral envelope synthesis in Moloney murine leukemia virus (MMLV).
Compound II was designed as a trifunctional inhibitor of either RT activity or
envelope synthesis or protease synthesis in MMLV. Administration of either I or
II to MMLV-infected mice for 3 weeks decreased viremia gradually to below the
level detectable by RT-PCR. Viremia did not reappear 8 weeks after termination of
treatment, when most of the mice were killed for autopsy. All infected but
untreated mice died within 6 months with enlarged spleens that exhibited abnormal
histologic signs and were found by PCR to contain the DNA of integrated viral
genome. The infected mice that had been treated subsequently with adequate dosage
of compound I or II had normal spleens, continued to live on, and had no
integrated MMLV genome in their spleen and bone marrow samples. The effective
i.p. dosage (ED50) for compounds I and II are 0.25 and 0.1 mg/kg, respectively,
which are 200-fold to 500-fold lower than that of the monofunctional RT inhibitor
poly-DNP-oligo A. The estimated effective oral dosage of compound II is 1.2
mg/kg.
PMID- 10192289
TI - Boranophosphates support the RNase H cleavage of polyribonucleotides.
AB - Modification of the phosphodiester linkages in DNA by replacing one of the
nonbridging oxygens with borane, BH3, produces an isoelectronic mimic of DNA
called boranophosphates. Nonstereoregular oligodeoxyribonucleoside all
boranophosphates are shown here for the first time to elicit the RNase H
hydrolysis of polyribonucleotides. We compared the ability of three types of
dodecamers (dodecathymidine phosphate, phosphorothioate, and boranophosphate) to
mediate the cleavage of poly(A) by Escherichia coli RNase H1. The rates of
poly(A) hydrolysis induced by boranophosphates were 76-fold (at 20 degrees C) and
18-fold (at 30 degrees C) greater than the rates induced by dodecathymidine
phosphate. In conjunction with the measured melting temperatures for each
heteroduplex, carried out under the same conditions as the RNAse H cleavage
experiments, the data establish an inverse relationship between the heteroduplex
thermostability and the rate of poly(A) hydrolysis. Chromatographic analysis
revealed another correlation: the higher the heteroduplex Tm, the higher the
pApA:pApApA ratio in the corresponding hydrolysates. The specific content of
these final products provides insight into the relative contribution of RNase H1
exonucleolytic/endonucleolytic mechanisms, with a low ratio for the lower melting
heteroduplexes reflecting more endonucleolytic-type hydrolysis. In total, our
data support the concept that antisense molecules with a weakened hybridization
potential enhance the rate of hydrolysis of RNA in RNA-DNA hybrids.
PMID- 10192290
TI - Comparison of binding of N3'-->P5' phosphoramidate and phosphorothioate
oligonucleotides to cell surface proteins of cultured cells.
AB - The binding of uniformly modified N3'-->P5' phosphoramidate and stereorandom and
stereopure phosphorothioate oligonucleotides (ODN) to cell surface proteins was
studied, using both a fibroblast and an epithelial cell line, to assess the
effect of different analog backbone types and base composition on cell surface
protein binding. Marked differences were observed, both quantitative and
qualitative, in the proteins to which individual ODN bound. One phosphoramidate,
antisense to the insulin-like growth factor-1 (IGF-1) receptor (IGF-1R), bound to
different proteins than did either a 6-base mismatch phosphoramidate IGF-1R
sequence or a sense N-ras sequence. The latter bound poorly to the fibroblast
line and predominantly to a 46 kDa protein in the epithelial line, as did many of
the other ODN. This binding was not so marked as that of the isosequential end
capped phosphodiester N-ras sequence, which bound to this protein in both cell
lines. Stereopure and stereorandom phosphorothioates containing a G-quartet
(shown in other studies to form high-order tetrad structures), antisense to c
myc, exhibited considerable nonspecific binding to many proteins, as did the
isosequential phosphoramidate. In particular, this ODN sequence gave notable
binding to high molecular weight proteins. In general, binding of the c-myc ODN
to proteins of 28-30, 46, 67, and 70-90 kDa was found in this study.
PMID- 10192291
TI - Cationic lipids employed for antisense oligodeoxynucleotide transport may inhibit
vascular cell adhesion molecule-1 expression in human endothelial cells: a word
of caution.
AB - Antisense oligodeoxynucleotides (ODN) have become a powerful tool to achieve
specific gene inhibition in various cell types, including endothelial cells. The
low spontaneous cellular uptake of ODN, however, usually requires the employment
of transmembrane carriers, such as the positively charged liposome formulation
dioleyloxypropyltrimethyl ammonium chloride/dioleoylphosphatidylethanolamine
(DOTMA/DOPE). In the present study, we observed that DOTMA/DOPE per se interferes
with the inducible expression of vascular cell adhesion molecule-1 (VCAM-1) in
human pulmonary artery endothelial cells (HPAEC). By RT-PCR analysis, a dose
dependent suppression of VCAM-1 but not intracellular adhesion molecule-1 (ICAM
1) mRNA levels in tumor necrosis factor-alpha (TNF-alpha)-challenged HPAEC
pretreated with DOTMA/DOPE (5-20 microg/ml) was demonstrated. Correspondingly, a
strong reduction of TNF-alpha-induced VCAM-1 but not ICAM-1 cell surface
expression on HPAEC was observed. These DOTMA/DOPE-induced changes were not due
to alterations in VCAM-1 mRNA stability, nor did DOTMA/DOPE inhibit TNF-alpha
induced NF-kappaB-like binding activity in nuclear extracts of HPAEC, as analyzed
by electrophoretic mobility shift assay. In contrast, DOTMA/DOPE effected a dose
dependent increase in AP-1-like binding activity in nuclear extracts of HPAEC, as
analyzed by Western blotting and EMSA. We conclude that positively charged
liposome preparations may per se inhibit TNF-alpha-induced endothelial VCAM-1
expression, and this may be related to changes in AP-1 but not NF-kappaB
dependent transcriptional control. Notably, when used at concentrations below 5
microg/ml, DOTMA/DOPE may be employed for specific antisense-mediated
downregulation of VCAM-1 in the absence of vehicle-related side effects on
adhesion molecule transcription.
PMID- 10192292
TI - Targeted cleavage of RNA molecules by human RNase P using minimized external
guide sequences.
AB - The endoribonuclease RNase P processes tRNA-like structures that are assembled
out of two separate strands. In these bimolecular constructs, one of the strands
is cleaved by the enzyme, and the other one is called the external guide sequence
(EGS). A number of EGS with different mutations and deletions were tested for the
ability to induce cleavage with human RNase P. Different domains of the original
tRNAtyr-like structure were deleted or modified. The anticodon stem and loop and
the variable loop could be deleted without a detrimental effect on recognition by
RNase P. Modifications in the lengths of T stem and aminoacyl acceptor stem led
to a decrease in the relative amount of cleavage, whereas modifications of the D
stem were more permissible. Single nucleotide deletions in the T loop reduced
cleavage to different extents, depending on the position. Values for the Kd of
complex formation of bimolecular constructs with annealing arms of varying
lengths ranged from 0.2 nM to 28 nM. A cleavage rate of 1 min(-1) was measured
for both the bimolecular target-EGS complex and tRNA precursor.
PMID- 10192293
TI - Intracellular localization of oligonucleotides: influence of fixative protocols.
AB - In many studies reporting the use of antisense oligonucleotides (ODN), the
intracellular localization was investigated by using fluorescent-labeled
oligonucleotides (F-ODN). More often, cells were fixed on uptake of F-ODN before
microscopic analysis. We report here the influence of various methods of cell
fixation on the intracellular localization of ODN. By confocal microscopy, we
show that with unfixed cells, endocytosed peptides, oligonucleotides (Mr around
10,000), and endocytosed proteins were mainly localized in vesicular
compartments. On mild fixation with paraformaldehyde, an identical intracellular
localization was observed repeatedly after fixation, from immediately up to
several days. In contrast, with methods based on the use of strong fixatives,
such as methanol or acetone, the small molecules diffuse into the cytosol and in
the case of oligonucleotides into the nucleus. These results point out the
importance of the fixation protocol in the study of intracellular localization of
ODN and their derivatives.
PMID- 10192294
TI - Efficient synthesis of DNA dumbbells using template-induced chemical ligation in
double-stranded polynucleotides closed by minihairpin fragments.
AB - The chemical ligation of 17 50-54-membered nicked DNA dumbbells with different
closing fragments, nick positions, and nucleotides facing the nick were
investigated. T4, T5, GTA4C, GCGA2GC, and GCGA3GC sequences were chosen as the
closing fragments. The nicks were placed in the center of the duplex stem or were
adjacent to the closing fragments. N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide
and cyanogen bromide were used as the condensing agents. We showed that the
ligation efficiency is 10%-90% depending on the sequence of the closing
fragments, nick position, and nucleotides facing the nick. Coupling yields of 80%
90% were observed when the nick was situated in the middle of the molecule
between two T residues or was adjacent to GCGA2GC or GCGA3GC minihairpins. In the
last case, the reacting 3'-phosphate and 5'-hydroxy groups were brought close
together by only two base pair minihairpins. The coupling yields did not depend
on the nature of the condensing agent. On the basis of the results obtained, we
believe a rational design of nicked DNA dumbbells has been developed for
efficient chemical synthesis of closed dumbbells.
PMID- 10192295
TI - Lack of evidence for antisense suppression in the fungal plant pathogen Ustilago
maydis.
AB - Modulation of the expression of the Ustilago maydis Pyr3 gene, encoding
dihydroorotase (DHOase), through antisense RNA regulation has been explored. This
was done by placing the gene in sense and antisense orientations under the
control of an hsp70-like gene promoter in a high-copy number autonomously
replicating expression vector. Cells transformed with the antisense vector
contained similar levels of DHOase activity to those found in cells harboring the
expression vector alone. Transformants containing the antisense vector did not
exhibit uridine-dependent growth, which would be expected for a Pyr3-deficient
phenocopy. This was despite detection of high levels of antisense RNA transcripts
in cells transformed with the Pyr3 antisense vector.
PMID- 10192296
TI - Brain as a unique antisense environment.
AB - During the last few years, antisense oligodeoxyribonucleotides (asODN) have
become a commonly used tool for blocking of gene expression in the mammalian
central nervous system. Successful gene inhibition has been reported for such
diverse targets as those encoding neurotransmitter receptors, neuropeptides,
trophic factors, transcription factors, cytokines, transporters, ion channels,
and others. This review presents a discussion of recent studies on ODN in the
brain, with a focus on specific approaches taken by the researchers in this field
and especially on peculiar features of this organ as a milieu for asODN action.
It is concluded that from the presented literature survey no coherent view on how
to rationally design ODN for brain studies has emerged.
PMID- 10192297
TI - Chronic myelogenous leukemia: from pathogenesis to therapy.
PMID- 10192298
TI - Validation of the Nordic flow cytometry standard for CD34+ cell enumeration in
blood and autografts: report from the third workshop. Nordic Stem Cell Laboratory
Group.
AB - Following two workshops on standardization of enumeration of CD34+ cells in blood
and leukapheresis products, the Nordic Stem Cell Laboratory Group (NSCL-G)
evaluated the Milan/Mulhouse/Nordic standard in clinical practice during the
third workshop (WS-III). This report documents an acceptable interlaboratory
variation in the most clinically active laboratories, with a coefficient of
variation (CV) below 0.19 in 7 of 8 analyses performed. The introduction of a pan
CD45 antibody in the analysis did not improve the CV. Comparison of two different
CD34 class II antibodies on a total of 99 samples and procedures with and without
washing on a total of 96 samples revealed a significant correlation (r2 >0.99)
for all analyses. Finally, subset analysis of uncommitted and lineage-specific
progenitors revealed major gating difficulties, indicating that further
improvements are necessary. In an analysis of more than 600 patients undergoing
mobilization and harvest of blood progenitors, with about 500 patients
autografted, we found a significant correlation between blood levels of CD34+
cells and recovery of CD34+ cells from each harvest as well as between CD34+ cell
number reinfused and time to neutrophil and platelet recovery. This report
documents for the first time that the very simple Milan/Mulhouse method (termed
The Nordic Standard) can be used by a group of laboratories to obtain important
clinical information. Consequently, we consider this method as the conventional
method in quality assessment of autografts, which should provide a benchmark for
development of second-generation improvements.
PMID- 10192299
TI - Injury to autologous normal tissues and tumors mediated by lymphokine-activated
killer (LAK) cells generated in vitro from peripheral blood mononuclear cells of
glioblastoma patients.
AB - Activation of peripheral blood mononuclear cells (PBMC) with IL-2 generates
lymphokine-activated killer (LAK) cells that show a broad target cell range. In
adoptive immunotherapy using in vitro-generated LAK cells, the intensity and
specificity of their cytotoxic activity affect the prognosis of cancer patients.
The present study was designed to examine the tumor-specific spectrum of T
lymphocytes generated from the PBMC of patients with recurrent glioblastoma by in
vitro propagation with IL-2 plus either soluble or solid-phase anti-CD3
monoclonal antibody (MAb) in short-term or long-term cultures. Both short-term
and long-term culturing with solid-phase anti-CD3 MAb plus IL-2 yielded broad
reactivity CD8+ alphabetaT and gammadeltaT lymphocytes, both of which were non
MHC restricted, as shown by the fact that they were able to lyse autologous
glioblastoma cells, MHC class I+II- allogeneic glioblastoma cells, and MHC class
I-II-NK-sensitive K562 target cells. More importantly, these cells from patients
failed to lyse fresh autologous PBMC. These results demonstrate that cells
generated using this approach are non-MHC-restricted LAK cells and exhibit marked
tumor specificity. In contrast, incubation with soluble anti-CD3 MAb generated T
lymphocytes that after long-term culture, were either CD4+ or CD8+. These caused
significant lysis of both allogeneic and autologous glioblastoma target cells,
the extent of lysis being greater than that using cells produced by culturing
with the solid-phase MAb. However, both the CD4+ and CD8+ cells also caused
greater lysis of autologous normal PBMC, indicating that cells generated using
this approach may cause significant adverse reactions in cancer patients if used
for immunotherapy.
PMID- 10192300
TI - Differential effects of IL-2 incubation on hematopoietic potential of autologous
bone marrow and mobilized PBSC from patients with hematologic malignancies.
AB - Culturing of hematopoietic progenitor cells for 24 h with IL-2 generates
cytotoxic effector cells that mediate in vitro and possibly in vivo antitumor
activity. We examined the effect of IL-2 incubation on progenitor cells from 24
patients with hematologic malignancies using paired autologous bone marrow (ABM)
and PBSC to determine differences in hematopoietic potential. Cells were
cryopreserved and stored in liquid nitrogen until conditioning therapy was
completed. After thawing, cells were incubated with IL-2 for 24 h at 37 degrees
C. Paired samples of ABM and PBSC from the same patient were analyzed for
nucleated and mononuclear cell number, CD34 antigen expression, and colony
forming unit (CFU) activity before and after IL-2 incubation. There was a
significant decrease in the average number of mononuclear cells (MNC) (x10(8)/kg)
(<0.001) and CD34+ cells (x10(6)/kg) (0.006) from both ABM and PBSC after 24 h IL
2 culture (ABM MNC: 0.6+/-0.1 vs. 0.4+/-0.0, p = <0.001; PBSC MNC: 4.4+/-0.5 vs.
3.7+/-0.4, p = 0.03; ABM CD34+: 2.4+/-0.5 vs. 1.3+/-0.3, p = <0.001; PBSC CD34+:
6.6+/-1.8 vs. 5.0+/-1.2, p = 0.05). However, whereas ABM CFU/10(5) MNC plated
(269.3+/-47.2 vs. 385.6+/-70.6) were significantly increased (p = 0.005), there
was no change in PBSC CFU (271.0+/-47.2 vs. 257.3+/-48.5). The mean plating
efficiency (%) of ABM CD34+ cells was markedly increased after IL-2 incubation
(10.1+/-3.3 vs. 19.0+/-7.2, p = 0.04), although it was lower than that of PBSC
CD34+ cells, which did not change significantly in culture (29.4+/-5.5 vs. 36.0+/
6.5). Additional work is in progress to determine the cause and significance of
the enhanced plating efficiency of the ABM progenitor cells.
PMID- 10192301
TI - Reproducible scoring of CFU-GM and BFU-E grown in collagen-based semisolid medium
after a short (3 h) training.
AB - Colony counting remains an important source of variation in colony-forming unit
granulocyte-macrophage (CFU-GM) assays performed in methylcellulose or agar. We
studied the reliability of colony scoring of CFU-GM assays carried out with
collagen, a matrix that allows gel collection on glass slides and in situ
cellular morphology. Fourteen slides were exchanged among laboratories, and two
rounds of colony (CFU-GM and burst-forming units-erythrocyte [BFU-E]) counting
were performed by 11 (first counting), then 8 (second counting) different
laboratories, the majority of which had no previous experience of collagen gel
cultures and reading. Two-way analysis of variance (ANOVA) of the first round of
colony counting showed significant differences among centers in CFU-GM counts (p
= 0.023) but not in BFU-E counts (p = 0.163). Coefficients of variation for the
14 slides ranged from 22% to 50% (median 28%) for CFU-GM counts and from 12% to
74% (median 23%) for BFU-E counts. After a 3 h session of collective colony
reading attended by members of 8 laboratories, a second round of colony counting
was performed. This time, ANOVA showed no significant difference among centers
for CFU-GM (p = 0.533) and BFU-E (p = 0.328) counts, and coefficients of
variation were significantly improved, with medians of 17% for CFU-GM counts and
20% for BFU-E counts. In addition, when data from the second round of readings
were analyzed without the 2 centers counting consistently low (center 8) or
consistently high (center 5), variance among centers was further improved for
both CFU-GM (p = 0.798) and BFU-E (p = 0.619). In summary, this study shows for
the first time that reproducible BFU-E and CFU-GM scoring can be achieved using
collagen-based semisolid medium (now commercially available) as long as adequate
training in colony identification is provided.
PMID- 10192302
TI - Use of reverse-transcriptase polymerase chain reaction (RT-PCR) for
carcinoembryonic antigen, cytokeratin 19, and maspin in the detection of tumor
cells in leukapheresis products from patients with breast cancer: comparison with
immunocytochemistry.
AB - This study evaluates the role of reverse-transcriptase polymerase chain reaction
(RT-PCR) assay for carcinoembryonic antigen (CEA), cytokeratin 19 (CK19), and
maspin transcripts to identify breast cancer cells (BCC) in leukapheresis
products (LP) collected from breast cancer (BC) patients and compares these
results with those obtained using immunocytochemistry (IC). Eighty-four LP
obtained from 33 patients with stage II-III BC and control subjects without BC
were screened for the presence of BCC by IC and CK19, CEA, and maspin expression
using RT-PCR. CEA RT-PCR and IC were the only specific markers, as no false
positives were detected in any patients without BC. CK19 RT-PCR gave 11% false
positives, whereas maspin RT-PCR with 25% was the most unspecific marker. In LP
from BC patients, positive results were observed in 70% and 63% for CK19 and CEA
RT-PCR, respectively. For maspin RT-PCR, this percentage was 22%, and for IC it
was 17%. There was a good correlation between the CEA and CK19 RT-PCR (p =
0.018). No correlation between CEA and CK19 RT-PCR and IC was found, and although
5 of the 6 IC+ samples were CEA+/CK19+, great discrepancies in the group of IC-
samples were observed. Our data suggest that RT-PCR assays for CEA and, to a
lesser extent, for CK19 have more sensitivity and specificity than IC to detect
BCC in LP.
PMID- 10192303
TI - In vitro culture of acute myelogenous leukemia blasts: a comparison of four
different culture media.
AB - Proliferative responses and cytokine secretion were compared when AML blasts were
cultured in the three serum-free media, X-Vivo 10, X-Vivo 15, and defined serum
free medium (IMDM with mercaptoethanol, low-density lipoprotein, albumin, and
transferrin) and in media containing 10% inactivated fetal bovine serum (FBS).
The following AML blast functions were investigated: (a) constitutive cytokine
secretion, (b) autonomous and cytokine-dependent proliferation, and (c) accessory
cell function during T cell activation. Constitutive cytokine secretion and
accessory cell function differed markedly when using different culture media. For
the constitutive AML blast secretion of IL-1beta, IL-6, and tumor necrosis factor
(TNF)-alpha, no qualitative differences were seen, but quantitative differences
were observed with decreased cytokine levels for cells cultured in X-Vivo 10 and
X-Vivo 15. The accessory cell function of AML blasts was also decreased in the X
Vivo media, whereas differences were less pronounced when comparing AML blast
proliferation. Our results clearly demonstrate that a well-characterized culture
system is essential for in vitro studies of AML blast functions.
PMID- 10192304
TI - A controlled comparison of two different clinical grade devices for CD34+ cell
selection of autologous blood stem cell grafts.
AB - Six patients who were to undergo autologous PBSC transplantation with positively
selected CD34+ cells were included in this study to compare the efficiency of two
devices for clinical grade stem cell selection, the Isolex 300i (Baxter, Munich,
Germany) and CEPRATE SC (CellPro, Bothell, WA). PBSC were mobilized by
chemotherapy and G-CSF and were collected by leukapheresis on a CS3000 cell
separator on 2 consecutive days. The two apheresis products were pooled for CD34
selection. The pooled apheresis products from each patient were divided into two
equal portions to be separated on each of the two devices. Cell selection was
performed according to the manufacturers' instructions. Enumeration of CD34+
cells was performed by flow cytometry using the HPCA-2 MAb. Purity and yield were
significantly better with Isolex than with CEPRATE. Median purity was 93.0%
(range 80%-98%) for Isolex and 61.5% (range 27%-72%) for CEPRATE (p = 0.03);
median yields for Isolex and for CEPRATE were 48.0% (range 18%-73%) and 23.0%
(range 17%-29%), respectively (p = 0.03). The number of CD34+ cells/kg body
weight was also significantly higher with Isolex (median 3.8x10(6), range 1.7
5.2) compared with CEPRATE (median 2.35x10(6), range 0.7-4.3) (p = 0.03). Thus,
the Isolex 300i device gave products of higher purity and recovered a higher
proportion of the CD34+ cells in the harvest before separation. The yield was
still poor with both devices, however, and further optimization of the technique
for clinical grade stem cell selection is warranted.
PMID- 10192305
TI - Tobacco smoke exposure at one month of age and subsequent risk of SIDS--a
prospective study.
AB - The aim of this investigation was to identify the sources of postnatal exposure
to tobacco smoke at 1 month of age and to examine their relation to sudden infant
death syndrome (SIDS). The Tasmanian Infant Health Survey was a prospective
cohort study undertaken from 1988 to 1995. It involved 9,826 infants (89% of
eligible infants) at higher risk of SIDS. Subsequently 53 eligible infants died
of SIDS. Hospital interviews were available on 51 and home interviews on 35 SIDS
infants. Urinary cotinine assays were conducted using gas-liquid chromatography
(n = 100). Within a predictive model that explained 63% of urinary cotinine
variance, the strongest predictor of cotinine and also of SIDS was maternal
smoking, though the effects of prenatal and postnatal smoking could not be
separated. However, for particular smoking-related behaviors, there was a
discordance between prediction of cotinine concentration and prediction of risk
of SIDS. If smoking mothers did not smoke in the room with the baby, the cotinine
level in the infant's urine was reduced by a little more than a half (p = 0.009),
but this was not associated with a reduction in SIDS risk (odds ratio = 1.09, 95%
confidence interval 0.47-2.55). Similarly, the presence of other adult resident
smokers was associated with a 63% increase in urinary cotinine (p = 0.047) but
not with increased SIDS risk (odds ratio = 0.69, 95% confidence interval 0.34
1.40). However, the study lacked the power to detect modest effects, that is,
those altering risk less than twofold.
PMID- 10192306
TI - Disentangling the separate effects of prenatal and postnatal smoking on the risk
of SIDS.
PMID- 10192307
TI - Maternal placental abnormality and the risk of sudden infant death syndrome.
AB - To determine whether placental abnormality (placental abruption or placental
previa) during pregnancy predisposes an infant to a high risk of sudden infant
death syndrome (SIDS), the authors conducted a population-based case-control
study using 1989-1991 California linked birth and death certificate data. They
identified 2,107 SIDS cases, 96% of whom were diagnosed through autopsy. Ten
controls were randomly selected for each case from the same linked birth-death
certificate data, matched to the case on year of birth. About 1.4% of mothers of
cases and 0.7% of mothers of controls had either placental abruption or placenta
previa during the index pregnancy. After adjustment for potential confounders,
placental abnormality during pregnancy was associated with a twofold increase in
the risk of SIDS in offspring (odds ratio = 2.1, 95% confidence interval 1.3
3.1). The individual effects of placental abruption and placenta previa on the
risk of SIDS did not differ significantly. An impaired fetal development due to
placental abnormality may predispose an infant to a high risk of SIDS.
PMID- 10192308
TI - Reproductive characteristics and the age at inception of the perimenopause in a
British National Cohort.
AB - Data from a British national cohort of women born in 1946 were used to
investigate the hypothesis that the rate of depletion of oocyte numbers is
associated with the age at which a woman reaches the inception of the
perimenopause. Menopausal status was obtained using an annual questionnaire, sent
to the cohort since the age of 47 years, and risk factor information from
contacts with the survey throughout earlier life. Parous women entered the
perimenopause later than nulliparous women. Those with the most children had the
latest perimenopause, where the estimated hazard ratio for women having four or
more children compared with those having none was 0.56 (95% confidence interval
0.39-0.81). Women who had a unilateral oophorectomy reached perimenopause earlier
then those who had not (hazard ratio = 1.96, 95% confidence interval 1.15-3.35).
There was some evidence that early age at menarche and short menstrual cycles
were associated with an earlier perimenopause. No relation was observed with oral
contraceptive pill use. Results provided some support for the hypothesis under
consideration, while estimates of the median age at inception of the
perimenopause due to these factors ranged from 46 to 50 years, which is an
important variation with respect to later health.
PMID- 10192310
TI - Serum dioxin and cancer in veterans of Operation Ranch Hand.
AB - We studied cancer prevalence and exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin
(dioxin) in veterans of Operation Ranch Hand, the Air Force unit responsible for
the aerial spraying of herbicides in Vietnam from 1962 to 1971. A comparison
group of Air Force veterans who served in Southeast Asia during the same period
and who were not involved with spraying herbicides was included. Comparison
veterans were matched to Ranch Hand veterans on age, race, and military
occupation. We measured dioxin in 1987 or 1992, extrapolated the result to the
time of service in Southeast Asia, and assigned each Ranch Hand veteran to
Background, Low, or High exposure categories. This study had low power to detect
an effect for specific or rare cancers. The risk of cancer at sites other than
the skin within 20 years of service was increased in the Low (odds ratio (OR) =
3.4, 95% confidence interval (CI) 1.5-8.0) and High (OR = 2.7, 95% CI 0.9-8.0)
categories, but the pattern was inconsistent with another study, suggesting that
the excess risk may not have been caused by dioxin exposure. Overall, we found no
consistent evidence of a dose-response gradient and no significant increase in
cancer risk in the High dioxin exposure category, the subgroup of greatest a
priori interest.
PMID- 10192309
TI - Plasma carotenoids, glutathione S-transferase M1 and T1 genetic polymorphisms,
and risk of hepatocellular carcinoma: independent and interactive effects.
AB - This study was conducted to assess the role of carotenoid and glutathione S
transferase (GST) M1 and T1 genetic polymorphisms in the development of
hepatocellular carcinoma (HCC). A total of 84 incident cases of HCC and 375
matched controls selected from a cohort of 7,342 men (4,841 chronic hepatitis B
carriers and 2,501 noncarriers) who were recruited between 1988 and 1992 in
Taiwan were studied. Neither GST M1/T1 polymorphisms nor plasma levels of various
carotenoids were independently associated with HCC, but they modulated smoking-
and/or drinking-related HCC risk. Cumulative exposure to tobacco smoke
significantly increased HCC risk in a dose-dependent manner among subjects with
low plasma beta-carotene levels (p for trend = 0.047) but not among those with
high levels. A statistically significant effect of habitual alcohol drinking on
HCC risk was observed only for those with low plasma levels of beta-carotene,
alpha-carotene, or lycopene and for GST M1 null subjects. There was evidence
suggesting an interaction between the GST M1/T1 genotype and certain carotenoids
in HCC associated with smoking and drinking. The strongest effect of smoking and
drinking was noted among GST M1 null subjects with low plasma levels of beta
carotene (smoking: adjusted odds ratio (OR) = 3.54, 95% confidence interval (CI)
1.06-11.83; drinking: OR = 8.28, 95% CI 2.40-28.61).
PMID- 10192311
TI - Smoking and the occurrence of Alzheimer's disease: cross-sectional and
longitudinal data in a population-based study.
AB - The authors tested the hypothesis that smoking exerts a protective effect on
Alzheimer's disease or dementia in a population-based cohort of 668 people aged
75-101 years (Sweden). Smoking was negatively associated with prevalent
Alzheimer's disease (adjusted odds ratio = 0.6, 95% confidence interval 0.4-1.1)
and dementia (adjusted odds ratio = 0.6, 95% confidence interval 0.4-1.0). Over 3
year follow-up (1989-1992), the hazard ratios of incident Alzheimer's disease and
dementia due to smoking were 1.1 (95% confidence interval 0.5-2.4) and 1.4 (95%
confidence interval 0.8-2.7). Mortality over 5-year follow-up was greater among
smokers in demented (hazard ratio = 3.4) than nondemented (hazard ratio = 0.8)
subjects. Smoking does not seem protective against Alzheimer's disease or
dementia, and the cross-sectional association might be due to differential
mortality.
PMID- 10192312
TI - Smoking, physical activity, and active life expectancy.
AB - The effect of smoking and physical activity on active and disabled life
expectancy was estimated using data from the Established Populations for
Epidemiologic Studies of the Elderly (EPESE). Population-based samples of persons
aged > or = 65 years from the East Boston, Massachusetts, New Haven, Connecticut,
and Iowa sites of the EPESE were assessed at baseline between 1981 and 1983 and
followed for mortality and disability over six annual follow-ups. A total of
8,604 persons without disability at baseline were classified as "ever" or "never"
smokers and doing "low," "moderate," or "high" level physical activity. Active
and disabled life expectancies were estimated using a Markov chain model.
Compared with smokers, men and women nonsmokers survived 1.6-3.9 and 1.6-3.6
years longer, respectively, depending on level of physical activity. When smokers
were disabled and close to death, most nonsmokers were still nondisabled.
Physical activity, from low to moderate to high, was significantly associated
with more years of life expectancy in both smokers (9.5, 10.5, 12.9 years in men
and 11.1, 12.6, 15.3 years in women at age 65) and nonsmokers (11.0, 14.4, 16.2
years in men and 12.7, 16.2, 18.4 years in women at age 65). Higher physical
activity was associated with fewer years of disability prior to death. These
findings provide strong and explicit evidence that refraining from smoking and
doing regular physical activity predict a long and healthy life.
PMID- 10192313
TI - Aging successfully until death in old age: opportunities for increasing active
life expectancy.
AB - The purpose of this study was to estimate the prevalence of having no disability
in the year prior to death in very old age and to examine factors associated with
this outcome. Participants were men and women aged 65 years and older who were
followed prospectively between 1981 and 1991 from three communities: New Haven,
Connecticut; Iowa and Washington counties, Iowa; and East Boston, Massachusetts.
Persons who died in late old age with known disability status within 15 months of
death (n = 1,097) were studied for predictors of dying without disability at the
last follow-up interview prior to death. The probability of a nondisabled 65-year
old man's surviving to age 80 and then being nondisabled prior to death was 26%
and, for a 65-year-old woman, the probability of surviving to age 85 and being
nondisabled before death was 18%. Physical activity was a key factor predicting
nondisability before death. There was nearly a twofold increased likelihood of
dying without disability among the most physically active group compared with
sedentary adults (adjusted odds ratio = 1.86, 95% confidence interval 1.24-2.79).
These findings provide encouraging evidence that disability prior to death is not
an inevitable part of a long life but may be prevented by moderate physical
activity.
PMID- 10192314
TI - Factor V Arg506Gln mutation is not associated with cardiovascular mortality in
older women.
AB - Factor V Arg506Gln is the most common genetic risk factor for venous thrombosis
and is associated with myocardial infarction in young women, especially among
smokers. The authors studied the relation of factor V Arg506Gln to cardiovascular
mortality in older women in a prospective cohort study of 12,239 women, living in
the city of Utrecht, who were initially aged between 52 and 67 years. Women were
followed on vital status between 1976 and 1995 (168,513 years). The factor V
Arg506Gln mutation was determined in urine samples of 524 women who died of
cardiovascular disease and in a reference group of 517 women who did not. Data
were analyzed using a nested case-referent analysis. Factor V Arg506Gln
heterozygosity was not associated with the risk of mortality by myocardial
infarction, cerebrovascular disease, and other cardiovascular disease, with
respective rate ratios and 95% confidence intervals being 1.1 (0.5-2.3), 1.2 (0.5
3.1), and 0.6 (0.2-1.7). No evidence of association was found in subgroups of
smokers and age. Factor V Arg506Gln is not a risk factor for cardiovascular
mortality in older women. Discrepancies with other studies may be explained by
different study populations, as age and sex may modify both the frequency of
cardiovascular disease and the effect of its risk factors.
PMID- 10192315
TI - Tuberculin skin testing among economically disadvantaged youth in a federally
funded job training program.
AB - Low income, medically underserved communities are at increased risk for
tuberculosis. Limited population-based national data are available about
tuberculous infection in young people from such backgrounds. To determine the
prevalence of a positive tuberculin skin test among economically disadvantaged
youth in a federally funded job training program during 1995 and 1996, the
authors evaluated data from medical records of 22,565 randomly selected students
from over 100 job training centers throughout the United States. An estimated
5.6% of students had a documented positive skin test or history of active
tuberculosis. Rates were highest among those who were racial/ethnic minorities,
foreign born, and (among foreign-born students) older in age (p < 0.001).
Weighted rates (adjusting for sampling) were 1.3% for white, 2.2% for Native
American, 4.0% for black, 9.6% for Hispanic, and 40.7% for Asian/Pacific Islander
students; rates were 2.4% for US-born and 32.7% for foreign-born students.
Differences by geographic region of residence were not significant after
adjusting for other demographic factors. Tuberculin screening of
socioeconomically disadvantaged youth such as evaluated in this study provides
important sentinel surveillance data concerning groups at risk for tuberculous
infection and allows recommended public health interventions to be offered.
PMID- 10192316
TI - Re: "Does body mass index adequately capture the relation of body composition and
body size to health outcomes?".
PMID- 10192317
TI - Re: "Does body mass index adequately capture the relation of body composition and
body size to health outcomes?".
PMID- 10192318
TI - Re: "Alcohol consumption and coronary heart disease morbidity and mortality".
PMID- 10192319
TI - Libraries offer incentive for web-based rivals to 'costly' journals.
PMID- 10192320
TI - California approves $1.5 billion campus.
PMID- 10192321
TI - Embattled French science agency says it is holding its own.
PMID- 10192322
TI - 'Don't try to change embryo research law'.
PMID- 10192323
TI - UK life scientists seek wider Foresight role.
PMID- 10192324
TI - Researchers face 'Catch-22' grants trap.
PMID- 10192325
TI - Is science dangerous?
PMID- 10192326
TI - At the roots of the mammalian family tree.
PMID- 10192327
TI - Olfaction. Good reception in fruitfly antennae.
PMID- 10192328
TI - Neurobiology. The eyes have it!
PMID- 10192329
TI - Fungal biology. Coming up for air and sporulation.
PMID- 10192330
TI - A spelling device for the paralysed.
PMID- 10192331
TI - Taxon sampling revisited.
PMID- 10192332
TI - A Chinese triconodont mammal and mosaic evolution of the mammalian skeleton.
AB - Here we describe a new triconodont mammal from the Late Jurassic/Early Cretaceous
period of Liaoning, China. This new mammal is represented by the best-preserved
skeleton known so far for triconodonts which form one of the earliest Mesozoic
mammalian groups with high diversity. The postcranial skeleton of this new
triconodont shows a mosaic of characters, including a primitive pelvic girdle and
hindlimb but a very derived pectoral girdle that is closely comparable to those
of derived therians. Given the basal position of this taxon in mammalian
phylogeny, its derived pectoral girdle indicates that homoplasies (similarities
resulting from independent evolution among unrelated lineages) are as common in
the postcranial skeleton as they are in the skull and dentition in the evolution
of Mesozoic mammals. Limb structures of the new triconodont indicate that it was
probably a ground-dwelling animal.
PMID- 10192333
TI - Anticipation of moving stimuli by the retina.
AB - A flash of light evokes neural activity in the brain with a delay of 30-100
milliseconds, much of which is due to the slow process of visual transduction in
photoreceptors. A moving object can cover a considerable distance in this time,
and should therefore be seen noticeably behind its actual location. As this
conflicts with everyday experience, it has been suggested that the visual cortex
uses the delayed visual data from the eye to extrapolate the trajectory of a
moving object, so that it is perceived at its actual location. Here we report
that such anticipation of moving stimuli begins in the retina. A moving bar
elicits a moving wave of spiking activity in the population of retinal ganglion
cells. Rather than lagging behind the visual image, the population activity
travels near the leading edge of the moving bar. This response is observed over a
wide range of speeds and apparently compensates for the visual response latency.
We show how this anticipation follows from known mechanisms of retinal
processing.
PMID- 10192334
TI - A new cellular mechanism for coupling inputs arriving at different cortical
layers.
AB - Pyramidal neurons in layer 5 of the neocortex of the brain extend their axons and
dendrites into all layers. They are also unusual in having both an axonal and a
dendritic zone for the initiation of action potentials. Distal dendritic inputs,
which normally appear greatly attenuated at the axon, must cross a high threshold
at the dendritic initiation zone to evoke calcium action potentials but can then
generate bursts of axonal action potentials. Here we show that a single back
propagating sodium action potential generated in the axon facilitates the
initiation of these calcium action potentials when it coincides with distal
dendritic input within a time window of several milliseconds. Inhibitory
dendritic input can selectively block the initiation of dendritic calcium action
potentials, preventing bursts of axonal action potentials. Thus, excitatory and
inhibitory postsynaptic potentials arising in the distal dendrites can exert
significantly greater control over action potential initiation in the axon than
would be expected from their electrotonically isolated locations. The coincidence
of a single back-propagating action potential with a subthreshold distal
excitatory postsynaptic potential to evoke a burst of axonal action potentials
represents a new mechanism by which the main cortical output neurons can
associate inputs arriving at different cortical layers.
PMID- 10192335
TI - Signalling through CD30 protects against autoimmune diabetes mediated by CD8 T
cells.
AB - Autoantigens found on pancreatic islets can move to draining lymph nodes, where
they are able to cause the activation and consequent deletion of autoreactive T
cells by a mechanism termed cross-tolerance. This deletion depends on signalling
through CD95 (also known as Fas), a member of the superfamily of tumour-necrosis
factor receptors. Here we describe a new mechanism that protects against
autoimmunity: this mechanism involves another member of this superfamily, CD30,
whose function was largely unknown. CD30-deficient islet-specific CD8-positive T
cells are roughly 6,000-fold more autoaggressive than wild-type cells, with the
transfer of as few as 160 CD30-deficient T cells leading to the complete
destruction of pancreatic islets and the rapid onset of diabetes. We show that,
in the absence of CD30 signalling, cells activated but not yet deleted by the
CD95-dependent cross-tolerance mechanism gain the ability to proliferate
extensively upon secondary encounter with antigen on parenchymal tissues, such as
the pancreatic islets. Thus, CD30 signalling limits the proliferative potential
of autoreactive CD8 effector T cells and protects the body against autoimmunity.
PMID- 10192336
TI - Effects of altered gene order or orientation of the locus control region on human
beta-globin gene expression in mice.
AB - The five human beta-type-globin genes, epsilon, Ggamma, Agamma, delta and beta,
are close together and are regulated by a locus control region (LCR) located at
the 5' end of the locus. Here we investigate the functional consequences of this
organization with respect to temporal regulation of the individual genes, by
using recombination techniques to invert the order of either the genes or the LCR
in vivo. Our analysis of transgenic mice bearing either normal or mutant
transgenes leads to two new observations. First, the position of the epsilon
globin gene next to the LCR is mandatory for its expression during the yolk-sac
stage of erythropoiesis. Second, LCR activity is orientation dependent, and so
the LCR does not act as a simple enhancer to stimulate transcription of the
globin genes. Thus, in the absence of any change in transgene integration
position, transgene copy number, trans-acting factors or other resident genetic
information, simple inversion of the human genes or the LCR fundamentally alters
the transcription of beta-type globin genes.
PMID- 10192337
TI - Chaperone-like activity of the AAA domain of the yeast Yme1 AAA protease.
AB - The AAA domain, a conserved Walker-type ATPase module, is a feature of members of
the AAA family of proteins, which are involved in many cellular processes,
including vesicular transport, organelle biogenesis, microtubule rearrangement
and protein degradation. The function of the AAA domain, however, has not been
explained. Membrane-anchored AAA proteases of prokaryotic and eukaryotic cells
comprise a subfamily of AAA proteins that have metal-dependent peptidase activity
and mediate the degradation of non-assembled membrane proteins. Inactivation of
an orthologue of this protease family in humans causes neurodegeneration in
hereditary spastic paraplegia. Here we investigate the AAA domain of the yeast
protein Yme1, a subunit of the iota-AAA protease located in the inner membrane of
mitochondria. We show that Yme1 senses the folding state of solvent-exposed
domains and specifically degrades unfolded membrane proteins. Substrate
recognition and binding are mediated by the amino-terminal region of the AAA
domain. The purified AAA domain of Yme1 binds unfolded polypeptides and
suppresses their aggregation. Our results indicate that the AAA domain of Ymel
has a chaperone-like activity and suggest that the AAA domains of other AAA
proteins may have a similar function.
PMID- 10192338
TI - Hyperfractionated radiotherapy in the management of diffuse intrinsic brainstem
tumors: when is enough enough?
PMID- 10192339
TI - Total skin electron beam therapy with or without adjuvant topical nitrogen
mustard or nitrogen mustard alone as initial treatment of T2 and T3 mycosis
fungoides.
AB - PURPOSE: To compare the efficacy of total skin electron beam therapy (TSEBT) with
or without adjuvant topical nitrogen mustard (+/- HN2) with topical nitrogen
mustard (HN2) alone as initial management of T2 and T3 mycosis fungoides (MF).
METHODS AND MATERIALS: A retrospective analysis of 148 patients presenting to
Stanford from January, 1970 through January, 1995 within 4 months of pathologic
diagnosis of MF. Fifty-five patients with T2 and 27 with T3 disease received
TSEBT +/- HN2. Fifty-four patients with T2 and 12 with T3 disease received HN2
alone. Boosts with radiotherapy were usually administered to cutaneous tumors of
patients with T3 disease. RESULTS: TSEBT +/- HN2 yielded significantly higher
complete response (CR) rates than did HN2 alone in patients with T2 and T3
disease (76% vs 39%, p = 0.03 for T2, and 44% vs 8%, p < 0.05 for T3,
respectively). In T2 disease, treatment with adjuvant HN2 was associated with a
longer freedom from relapse following TSEBT when compared to observation
following a CR to TSEBT (p = 0.068). However, no significant differences in
survival were observed for different management programs for T2 or T3 disease. In
T2 disease, both TSEBT and HN2 were as effective as salvage therapy as when
utilized as initial therapy. However, salvage therapy in T3 disease was rarely
effective. Limited tumor involvement in T3 disease did not correlate with
improved survival compared to more generalized tumorous disease. MF contributed
to 27% and 68% of deaths in patients with T2 and T3 disease, respectively.
CONCLUSION: Because of high response rates, management of significantly
symptomatic or extensive T2 MF should include TSEBT, and adjuvant HN2 should be
administered after a CR to TSEBT. Patients with T2 disease who fail TSEBT or HN2
can be salvaged with the other modality. TSEBT is also an effective treatment for
T3 disease. The small subset of patients with limited T3 disease may also be
treated with HN2 and local radiotherapy to the tumors. Further investigations are
necessary to improve the overall outcome for T3 mycosis fungoides.
PMID- 10192340
TI - There is no role for hyperfractionated radiotherapy in the management of children
with newly diagnosed diffuse intrinsic brainstem tumors: results of a Pediatric
Oncology Group phase III trial comparing conventional vs. hyperfractionated
radiotherapy.
AB - PURPOSE: In June 1992, POG began accrual to a phase III study, POG-9239, designed
to compare the time to disease progression, overall survival, and toxicities
observed in children with newly diagnosed brainstem tumor treated with 100 mg/m2
of infusional cisplatin and randomized to either conventional vs.
hyperfractionated radiotherapy. METHODS AND MATERIALS: Patients eligible for
study were those between 3 and 21 years of age with previously untreated tumors
arising in the pons. Histologic confirmation of diagnosis was not mandatory,
provided that the clinical and MRI scan findings were typical for a diffusely
infiltrating pontine lesion. Treatment consisted of a six-week course of local
field radiotherapy with either once a day treatment of 180 cGy per fraction to a
total dose of 5400 cGy (arm 1) or a twice a day regimen of 117 cGy per fraction
to a total dose of 7020 cGy (the second of the three hyperfractionated dose
escalation levels of POG-8495) (arm 2). Because of previously reported poor
results with conventional radiotherapy alone, cisplatin was included as a
potential radiosensitizer in an attempt to improve progression-free and ultimate
survival rates. Based on results of the phase I cisplatin dose escalation trial,
POG-9139, 100 mg/m2 was chosen for this trial and was delivered by continuous
infusion over a 120-hour period, beginning on the first day of radiotherapy and
repeated during weeks 3 and 5. One hundred thirty eligible patients were treated
on protocol, 66 on arm 1 and 64 on arm 2. RESULTS: The results we report are from
time of diagnosis through October 1997. For patients treated on arm 1, the median
time to disease progression (defined as time to off study) was 6 months (range 2
15 months) and the median time to death 8.5 months (range 3-24 months); survival
at 1 year was 30.9% and at 2 years, 7.1%. For patients treated on arm 2, the
corresponding values were 5 months (range 1-12 months) and 8 months (range 1-23
months), with 1- and 2-year survival rates at 27.0% and 6.7%, respectively.
Evaluation of response by MRI at 4 or 8 wks post treatment was available in 108
patients and revealed a complete response in 1 patient of each Rx arm, a partial
response (> 50% decrease in size) in 18 patients of arm 1 and 15 patients of arm
2, minimal to no response (stable) in 25 patients of arm 1 and 23 patients of arm
2, and progressive disease in 13 patients of arm 1 and 12 patients of arm 2. The
pattern of failure was local in all patients. Morbidity of treatment was similar
in both Rx arms, with no significant toxicity (including hearing loss) reported.
Autopsy was performed in 6 patients, and confirmed the presence of extensive
residual tumor in these cases. CONCLUSION: The major conclusion from this trial
is that the hyperfractionated method of Rx 2 did not improve event-free survival
(p = 0.96) nor did it improve survival (p = 0.65) over that of the conventional
fractionation regimen of Rx 1, and that both treatments are associated with a
poor disease-free and survival outcome.
PMID- 10192341
TI - Predictors of subclinical nodal involvement in clinical stages I and II non-small
cell lung cancer: implications in the inoperable and three-dimensional dose
escalation settings.
AB - PURPOSE: When mediastinal lymph nodes are clinically uninvolved in the setting of
inoperable non-small cell lung cancer, whether conventional radiation techniques
or three-dimensional dose-escalation techniques are used, the benefit of elective
nodal irradiation is unclear. Inclusion of the clinically negative mediastinum in
the radiation portals increases the risk of lung toxicity and limits the ability
to escalate dose. This analysis represents an attempt to use clinical
characteristics to estimate the risk of subclinical nodal involvement, which may
help determine which patients are most likely to benefit from elective nodal
irradiation. METHODS: From 1987 to 1990, 346 patients undergoing complete
resection of non-small cell lung cancer underwent a preoperative computed
tomographic scan revealing no clinical evidence of N2/N3 involvement.
Multivariate regression and regression tree analyses attempted to define which
patients were at highest risk for subclinical mediastinal involvement (N2) and
which patients were at highest risk for subclinical N1 and/or N2 involvement
(N1/N2). Immunohistochemical data suggest that the conventional histopathologic
techniques used during this study somewhat underestimate the true degree of lymph
node involvement; therefore, a third end point was also evaluated: N1 involvement
and/or N2 involvement and/or local-regional recurrence (N1/N2/LRR). RESULTS:
Regression analyses revealed that the following factors were independently
associated with a high risk of more advanced disease: positive preoperative
bronchoscopy (N2, p = 0.02; N1/N2, p < 0.0001; N1/N2/LRR, p < 0.001) and tumor
grade 3/4 (N1/N2/LRR, p < 0.01). A regression tree analysis was then used to
separate patients into risk groups with respect to N1/N2/LRR. CONCLUSION: In
inoperable non-small cell lung cancer, the patients for whom mediastinal
radiation therapy may most likely be indicated are those with a positive
preoperative bronchoscopy, especially with large (> 3 cm) primary tumors.
PMID- 10192342
TI - Feasibility and tolerance of pulsed dose rate interstitial brachytherapy.
AB - PURPOSE: Pulsed dose rate (PDR) treatment is a new approach that associates the
physical advantages of high-dose-rate (HDR) technology with the potential
radiobiological advantages of low-dose-rate (LDR) brachytherapy. This
retrospective study analyzes the feasibility, toxicity, and preliminary oncologic
results in a series of 43 patients treated with PDR interstitial brachytherapy.
METHODS AND MATERIALS: Twenty-four patients with pelvic, 17 patients with head
and neck, and 2 patients with breast cancers were treated. Twenty-eight patients
had primary and 15 recurrent tumors; 14 had received prior external irradiation
to the same site. The doses per pulse at the prescription isodose were 0.4-1 Gy
(median 0.5 Gy), delivered using a single cable-driven 0.3-1.0 Ci 192-iridium
source (PDR Nucletron Micro-Selectron). RESULTS: The median treated volumes (at
the prescribed isodose) were 28 cc for pelvic, 8.33 cc for head and neck, and 40
cc for breast malignancies. Of 14,499 source and 14,499 dummy source transfer
procedures, 3 technical machine failure events were observed (0.02%). Grade 3
acute toxicities were seen in 5/43 patients (4 oral stomatitis, 1 vaginal
mucositis) and grade 4 acute toxicity in one patient (rectovaginal fistula).
Grade 3-4 late complications were observed in 4/41 (9.8%) patients: 1 pubic
fracture, 1 rectovaginal fistula, 1 vesicovaginal fistula and 1 local necrosis.
With a median follow-up of 18 months, 10/41 patients progressed locoregionally (6
pelvic, 4 head and neck), 3 developed local recurrence and distant metastasis (3
pelvic), 3 only distant metastasis (2 pelvic, 1 head and neck). Two patients are
lost to follow-up. CONCLUSION: PDR interstitial brachytherapy for pelvic, head
and neck, and breast malignancies is feasible and the acute and late toxicities
seem acceptable. Although the physical advantages of PDR are clear, further
follow-up is required to determine how results compare with those obtained with
standard LDR brachytherapy.
PMID- 10192343
TI - Permanent 125iodine implants for recurrent malignant gliomas.
AB - PURPOSE: To determine the efficacy and toxicity of permanent 125iodine implants
for recurrent malignant gliomas. METHODS AND MATERIALS: Between January 1989 and
January:, 59 patients with histologically confirmed recurrent malignant gliomas
(22 nonglioblastoma malignant gliomas, 37 glioblastoma multiforme at the time of
implant) received a permanent 125iodine implant. Patients ranged in age from 13
74 years. The median ages for the overall group, nonglioblastoma (nonGBM), and
glioblastoma (GBM) groups was 47 years, 39 years, and 53 years, respectively.
RESULTS: With a median follow-up of 40 months, the median survival for the 59
total patients is 1.34 years; nonGBM 2.04 years, GBM 0.9 years. Factors
predictive for poor prognosis were GBM histology, age 60 years or more, target
volume 17 cc or more, and/or tumor location within the corpus callosum or
thalamus. Reoperations have been performed in 24 (40%) patients; 15 (25%) for
tumor progression; 3 (5%) for radiation necrosis; 2 (3%) for skull
necrosis/infection, and 4 (7%) for other reasons (Ommaya reservoir insertion,
catheter removal, hematoma evacuation). CONCLUSION: Permanent 125iodine implants
in selected patients with recurrent malignant gliomas are associated with
reasonable long-term survival and a low risk of complications. Given the low
incidence of radiation necrosis, future plans are to increase dose rate and/or
total dose delivered with the permanent implant.
PMID- 10192344
TI - The relationship between dose heterogeneity ("hot" spots) and complications
following high-dose rate brachytherapy.
AB - PURPOSE: It is generally believed that "hot" spots should be avoided in
radiotherapy because they lead to complications. Dose homogeneity within the
target volume is much more difficult to achieve during brachytherapy than during
external beam irradiation, and implants are rarely geometrically perfect. To not
underdose some parts of the target volume, therefore, it may be necessary to
accept hot spots in other parts of the target volumes, but it is not at all clear
from the literature how much dose heterogeneity should be considered excessive.
We undertook this study in an effort to determine just how high a dose to a hot
spot is associated with clinically significant complications. METHODS AND
MATERIALS: We studied 40 patients treated by high-dose rate brachytherapy with or
without external irradiation. For each patient, we calculated the minimum dose to
the "hottest" 1 cubic centimeter (cc) volume (Dmax1) and, for 18 patients, the
minimum dose to the hottest 10 cc volume (Dmax10) as well. RESULTS: Considerable
dose heterogeneity existed within the target volume. The Dmax1 ranged from 150
2000% (median 320%) of the minimum target dose (MTD). The median MTD/fraction was
2.50 Gy (range 1.50-25.00), and the median Dmax1/fraction was 10.00 Gy (range
3.75-150.00). The median Dmax1 from the entire course of brachytherapy was 75.00
Gy (range 25.00-550.00). Adding the doses from planned external irradiation, plus
any prior irradiation to the same area, the median total Dmax1 was 112.50 Gy
(range 30.00-580.00), yet the incidence of complications, even among those in the
highest quartile of this dose range, was not greater than the lowest quartile.
The total median Dmax10 was 85.00 Gy (range 32.00-130.00), but the incidence of
complications was, again, similar whether the dose was in the lower or the upper
half of this range (32.00-85.00 Gy, or 86.00-130.00 Gy, respectively).
CONCLUSIONS: We had expected to find that the patients with the highest Dmax1
and/or Dmax10 would be the ones most likely to suffer complications, but the
results did not support this hypothesis. Thus, dose heterogeneity, within the
scope of our study, turned out to be rather unimportant with regard to
complications. This finding contradicts the conventional wisdom and suggests that
concerns about hot spots need not preclude optimization to ensure adequate dosage
to all parts of the target volume.
PMID- 10192345
TI - Perioperative fractionated high-dose rate brachytherapy for malignant bone and
soft tissue tumors.
AB - PURPOSE: To investigate the viability of perioperative fractionated HDR
brachytherapy for malignant bone and soft tissue tumors, analyzing the influence
of surgical margin. METHODS AND MATERIALS: From July 1992 through May 1996, 16
lesions of 14 patients with malignant bone and soft tissue tumors (3
liposarcomas, 3 MFHs, 2 malignant schwannomas, 2 chordomas, 1 osteosarcoma, 1
leiomyosarcoma, 1 epithelioid sarcoma, and 1 synovial sarcoma) were treated at
the Osaka University Hospital. The patients' ages ranged from 14 to 72 years
(median: 39 years). Treatment sites were the pelvis in 6 lesions, the upper limbs
in 5, the neck in 4, and a lower limb in 1. The resection margins were classified
as intracapsular in 5 lesions, marginal in 5, and wide in 6. Postoperative
fractionated HDR brachytherapy was started on the 4th-13th day after surgery
(median: 6th day). The total dose was 40-50 Gy/7-10 fr/4-7 day (bid) at 5 or 10
mm from the source. Follow-up periods were between 19 and 46 months (median: 30
months). RESULTS: Local control rates were 75% at 1 year and 48% in 2 years, and
ultimate local control was achieved in 8 (50%) of 16 lesions. Of the 8
uncontrolled lesions, 5 (63%) had intracapsular (macroscopically positive)
resection margins, and all the 8 controlled lesions (100%) had marginal
(microscopically positive) or wide (negative) margins. Of the total, 3 patients
died of both tumor and metastasis, 3 of metastasis alone, 1 of tumor alone, and 7
showed no evidence of disease. Peripheral nerve palsy was seen in one case after
this procedure, but no infection or delayed wound healing caused by tubing or
irradiation has occurred. CONCLUSION: Perioperative fractionated HDR
brachytherapy is safe, well tolerated, and applicable to marginal or wide
surgical margin cases.
PMID- 10192346
TI - A new method for the placement of brachytherapy probes in paranasal sinus and
nasopharynx neoplasms.
AB - PURPOSE: In afterloading therapy, the exact placement of the applicator is
crucial for the result of radiotherapy. A deviation of few millimeters from the
target leads to a significant reduction of radiation energy to the tumor. METHODS
AND MATERIALS: We present a new method using a computer-assisted device for three
dimensional placing of afterloading probes based on CT scans that allows for the
exact placement. RESULTS: Target points have been reached with an accuracy of 0.6
mm. Since 1991 we have used this technique for 24 clinical applications in 11
patients with recurrent neoplasms in the region of the paranasal sinuses and
nasopharynx for palliative treatment. CONCLUSIONS: The presented method is a
reliable and precise procedure for the positioning of afterloading probes,
avoiding the inaccuracy of the traditional methods.
PMID- 10192347
TI - An initial experience using concurrent paclitaxel and radiation in the treatment
of head and neck malignancies.
AB - BACKGROUND: Combined modality therapy plays a central role in the management of
head and neck malignancies. This study examined the feasibility and preliminary
results of treating a group of patients using concurrent bolus paclitaxel (Taxol)
and radiation therapy. METHODS: Fourteen patients with a median age of 56 years
(range 42-81) were treated. Paclitaxel was given every 3 weeks at a dose of 100
mg/m2 concurrently with external beam radiation. The patients treated included
those who had failed to achieve a complete response (CR) to induction
chemotherapy with cisplatin, 5-fluorouracil, and leucovorin (PFL), or who had
locally advanced disease not previously treated. RESULTS: Median follow-up from
the initiation of treatment is 40 months (range 23-48). The majority of patients
(13/14) achieved clinical CRs at the primary site. The development of responses
was characterized by a long time course. Three patients who were nonresponders
(NRs) to induction PFL chemotherapy were treated. One was a clinical CR at the
primary site, one did not achieve a CR, and the other had residual disease in the
neck. Four patients have failed, one with local-regional disease, one with a
marginal failure, one with distant metastases, and one was not rendered disease
free by the treatment. As expected, significant local toxicity was observed. Most
patients were managed with the aid of a percutaneous endoscopic gastrostomy
(PEG). Two patients experienced significant moist desquamation and required
treatment breaks of greater than 1 week. CONCLUSION: Paclitaxel can be given on a
3-week schedule at 100 mg/m2 concurrently with radiation. The preliminary results
indicate good local responses and acceptable toxicity. This treatment approach
merits further study in the treatment of head and neck malignancies, and should
be considered as an option in other sites.
PMID- 10192348
TI - Prognostic factors for local control of early glottic cancer: the Rabin Medical
Center retrospective study on 207 patients.
AB - PURPOSE: Different radiation therapy schedules and devices have been used over
the last 20 years at Rabin Medical Center in patients with early glottic cancer.
The aim of the present retrospective analysis was to identify the subgroup of
patients at high risk of failure of radiation treatment. MATERIALS AND METHODS:
Between 1974 and 1994, 207 patients with squamous cell carcinoma of the glottis,
182 Stage T1 and 25 Stage T2, underwent definitive radiation therapy. During this
period, treatment was administered with different radiation devices (60Co or 6-MV
X ray), using different dose/fraction protocols (1.8 or 2 Gy per day, 5 or 6
fractions per week), total doses (42-77.4 Gy), overall radiation times, and
delays. These treatment variables, in addition to certain patient and tumor
characteristics, were correlated with local control at a median follow-up of 57
months (range 18-265 months). RESULTS: The 5-year local control rates for T1 and
T2 tumors were 88% and 73%, respectively. Univariate analysis showed that
smoking, diabetes mellitus, anterior commissure involvement, T stage, and
extension of tumor to one third or more of the vocal cord were highly
significantly correlated with decreased local control. None of the treatment
variables, including dosage at which complete tumor regression was noted, were
found to be predictive. By multivariate analysis, only anterior commissure
involvement was found to be highly significant (risk ratio 1.9, 95% CI 1.2-3.0, p
= 0.027), and T stage was borderline significant (risk ratio 1.6, 95% CI 1.0-2.5,
p = 0.054). CONCLUSION: This study suggests that only two tumor characteristics
are predictive of local failure of early glottic cancer: anterior commissure
involvement and T stage. Treatment variables apparently do not influence local
control.
PMID- 10192349
TI - Apoptosis in carcinoma of the bladder: relation with radiation treatment results.
AB - PURPOSE: Radiotherapy is widely used in the treatment of bladder cancer. The
search for biological parameters that could select patients who will respond to
radiation treatment has become essential. The aim of this study is to assess
whether the pretreatment apoptotic index is useful in predicting local control
and survival in a group of bladder cancer patients treated by radiotherapy.
METHODS AND MATERIALS: Fifty-five patients with invasive bladder carcinoma
treated between 1983 and 1996 were included in this study. Radiotherapy was given
to a median dose of 66 Gy, mean 63.28 Gy, in 1.8-2 Gy daily fractions. Apoptotic
cells were studied in hematoxylin-eosin slides. Clinicopathological tumor
characteristics were studied in relation to the apoptotic index, and as
prognostic factors for local control and survival in both univariate and
multivariate analysis. RESULTS: Pretreatment apoptotic indexes were related to
tumor stage, mitotic index, and Ki67 proliferation index. Five-year actuarial
local control for the whole group was 45%. Patients with tumors showing low
pretreatment apoptotic indexes had better local control (p < 0.037) and survival
(p < 0.01) than highly apoptotic tumors. Tumor stage (T2 vs. T3-4) and the
pretreatment apoptotic index were significant predictive factors for local
control and survival in multivariate analysis. CONCLUSIONS: The pretreatment
apoptotic index is useful in predicting the clinical outcome of bladder cancer
patients treated by radiotherapy. Assessment of biological tumor characteristics
could allow the selection of patients for different treatment strategies.
PMID- 10192350
TI - Rectal dosimetric analysis following prostate brachytherapy.
AB - PURPOSE: To retrospectively assess the rectal tolerance dose in transperineal
ultrasound-guided prostate brachytherapy using easily measured point doses.
METHODS AND MATERIALS: Forty-five consecutive patients who underwent prostate
seed implantation from January 1996 to October 1996, using either 125I or 103Pd
as monotherapy or as a boost following 45 Gy of external beam radiotherapy (XRT),
were evaluated. For monotherapy using 125I, the minimal peripheral dose (mPD) was
160 Gy, utilizing dosimetry parameters which are equivalent to 144 Gy under the
American Association of Physicists in Medicine Task Group 43 (AAPM TG43)
recommendations. Computed tomography (CT)-based dosimetry was performed within 9
days of the implant, with a urinary catheter in place for identification of the
urethra, and a rectal obturator positioned prior to the CT scan for
identification of the anterior rectal mucosa. Dosimetric parameters relevant to
this study were the average, maximal and minimal anterior rectal mucosal dose,
and the surface area and length of the anterior rectal mucosa irradiated to 50%,
75%, 90%, 100%, and 120% of the prescribed dose. Rectal complications were
determined by patient reporting during office visits and telephone follow-up.
Follow-up ranged from 19 to 28 months (median 23). RESULTS: Among the four
cohorts, the average anterior rectal mucosal dose as a percent of the prescribed
mPD was 82.5% +/- 14.1% (standard deviation, SD), and the average maximum was
120% +/- 35%. The length of the rectum receiving a given dose was found to be
correlated with the rectal surface area receiving that dose (r2 = 0.82 - 0.93
over the dose range 0.5-1.2 mPD). Rectal complications occurred in only four
patients, and consisted of mild, self-limited proctitis. Three of the four were
in the top quartile of average and maximal rectal dose and length of rectum
receiving > or = 100% of mPD, while the fourth was in the bottom quartile of
these parameters. In terms of surface area, all four patients were in the upper
half of the study group, with > or = 90 mm2 at dose levels > or = 100% of mPD.
CONCLUSION: Our results indicate that in an implant program which maintains the
anterior rectal mucosa point dose averages to about 85% of the prescribed dose
(regardless of the choice of isotope or the treatment approach), the average
maximum to 120% of mPD, and the length of the anterior rectal mucosa receiving
100% and 120% of the prescribed dose at approximately 10 mm and 5 mm,
respectively, the incidence of mild self-limited proctitis will be in the range
of approximately 9%, without incidence of rectal ulceration and/or fistula
formation.
PMID- 10192351
TI - Outcomes in breast cancer patients relative to margin status after treatment with
breast-conserving surgery and radiation therapy: the University of Pennsylvania
experience.
AB - PURPOSE: To evaluate the significance of final microscopic resection margin
status on treatment outcomes in women with early breast cancer who are treated
with breast-conserving surgery and definitive breast irradiation. METHODS AND
MATERIALS: An analysis was performed of 1021 consecutive women with clinical
Stage I or II invasive carcinoma of the breast treated with breast-conserving
surgery and definitive breast irradiation. Complete gross excision of tumor was
performed in all cases, and an axillary staging procedure was performed to
determine pathologic axillary lymph node status. The 1021 patients were divided
into four groups based on the final microscopic margin from the tumor excision or
from the re-excision if performed. These four groups were: (a) 518 patients with
negative margins; (b) 124 patients with focally positive margins; (c) 96 patients
with focally close margins (< or = 2 mm); and (d) 283 patients with unknown
margins. RESULTS: Local failure was not significantly different in patients with
negative, focally positive, focally close or unknown final pathologic margins of
resection at 8 years (8% vs. 10% vs. 17% vs. 16%, respectively, p = 0.21). The 8
year outcome also was not different among the four groups for overall survival
(86% vs. 83% vs. 88% vs. 81%, respectively, p = 0.13), cause-specific survival
(89% vs. 86% vs. 88% vs. 83%, respectively, p = 0.14), no evidence of disease
survival (81% vs. 73% vs. 86% vs. 77%, respectively, p = 0.09), and freedom from
distant metastases (85% vs. 75% vs. 86% vs. 79%, respectively, p = 0.08).
CONCLUSION: These results demonstrate that selected patients with focally
positive or focally close microscopic resection margins can be treated with
breast-conserving surgery and definitive breast irradiation with 8-year local
control rates and survival rates that are similar to those seen in breast
conservation patients with negative or unknown final resection margins.
PMID- 10192352
TI - A mobile shield to reduce scatter radiation to the contralateral breast during
radiotherapy for breast cancer: preclinical results.
AB - PURPOSE: To design a practical breast shield and to investigate its efficacy in
reducing scattered radiation to the contralateral breast of patients undergoing
radiation therapy for breast cancer. METHODS AND MATERIALS: We constructed a
mobile shield consisting of (a) a mobile base and a counterweight; (b) a vertical
column adjustable in height and a diagonal arm adjustable in angle; (c) a curved,
2.5-cm thick lead sheet with a 1-cm thick polystyrene liner for blocking
scattered radiation; and (d) diode detectors to verify that the edge of the lead
sheet is not in the useful beam in addition to the use of the field light.
Measurements were performed with thermoluminescent dosimeters on 10 patients
without the shield and on an anthropomorphic phantom with a pair of wax breasts
with and without the shield. All of the patients were treated with 6-MV photons
(Varian 6/100). The scattered radiation from the medial and lateral fields was
measured separately. RESULTS: The contribution of the medial field to the total
scattered dose was 70% to 75%, whether a medial wedge was used or not. However,
without a medial wedge, the scattered dose was reduced by nearly 33% at 3 to 9 cm
away from the medial border. In the anthropomorphic phantom study with wax
breast, the mobile shield reduced the medial field contribution to the total
scatter dose to less than the contribution from the lateral field without a
shield. With a prescribed dose of 50 Gy and a medial wedge, the median scatter
dose to the contralateral breast from 6 patients was 5.3 Gy; without a medial
wedge, it was 3.8 Gy from 4 patients at 6 cm from the medial border. In the
phantom study, with the shield the total dose to the contralateral breast was 1.0
Gy at 6 cm from the medial border with a same prescribed dose. CONCLUSION: The
mobile shield reduced the scatter dose to the contralateral breast from the
linear accelerator (Varian 6/100, 6-MV photons) by a factor of 3 to 4. The shield
greatly reduced the scattered dose in the wax phantom. Equivalent reductions in
patients may be clinically significant by reducing the risk of radiation-induced
breast cancer in the contralateral breast of woman undergoing radiation therapy
for breast cancer. The shield is safe and easy to adjust to each patient.
PMID- 10192353
TI - The accuracy of transrectal ultrasound in predicting the pathological stage of
low-lying rectal cancer after preoperative chemoradiation therapy.
AB - PURPOSE: There has been a growing interest in the use of preoperative radiation
therapy in rectal cancer treatment in the last years. The need for accurate
preoperative staging is important so as to avoid overtreatment in stage I
patients, and to select patients who require downstaging prior to surgery as they
are technically inoperable. While transrectal ultrasound (TRUS) has been reported
to accurately stage preoperative patients, its efficacy postradiation has been
questioned. The authors report a series studied by TRUS to contribute to the
discussion on the role of this method. METHODS AND MATERIALS: Twenty-eight
patients with rectal cancer were accrued. Twenty-six patients, clinically staged
T2-T4 or/and N1-N3 between March 1990 to October 1993, underwent preoperative
chemoradiation. Two patients (T2N0) were treated by local excision and
postoperative radiotherapy. Following therapy and just before surgery, each
patient was restaged by TRUS. These results were subsequently compared with a
pathological stage of resected specimen for both the primary tumor (T) and
regional lymph nodes (LN). RESULTS: The accuracy of TRUS for T stage after
chemoradiation was 92.8% (positive predictive value [PPV] 94.4%, negative
predictive value [NPV] 90.0%). The accuracy for LN staging after chemoradiation
was 60.7% (PPV 100.0%, NPV 54.0%), because LN located outside the scanning range
were missed. CONCLUSION: Based on our results, we conclude that TRUS of the
primary tumor is an accurate staging technique for patients with rectal cancer
treated with preoperative chemoradiation.
PMID- 10192354
TI - Occult carcinoma discovered after simple hysterectomy treated with postoperative
radiotherapy.
AB - PURPOSE: Treatment of patients with occult carcinoma of the cervix discovered
after simple hysterectomy is controversial. The purpose of this review is to
examine our results with postoperative radiotherapy and to compare them to
similar reports and to reports of treatment with radical parametrectomy. METHODS
AND MATERIALS: Between November 1979 and April:, 18 patients were treated with
radiotherapy at the University of Virginia for invasive carcinoma of the cervix
discovered after simple hysterectomy. Simple hysterectomy was performed in all 18
patients for a variety of indications. After surgery gross residual carcinoma
remained in four patients; and microscopic disease was present at the surgical
margins in two patients. The remaining patients had no evidence of residual
disease. All 18 patients had postoperative radiotherapy with or without
brachytherapy. The endpoints for this study were local control, survival, and
treatment-related toxicity. Actuarial rates were calculated using the Life Table
method. RESULTS: Median follow-up for all 18 patients was 42 months (range 2-202
months). Both the 5 and the 10-year actuarial local control rates were 88%. Five
and 10-year actuarial overall survival rates were both 93%. Two patients had both
local and distant cancer recurrences. There were no recurrences among the six
patients treated with external beam alone. The remaining patients are all alive
without evidence of disease, including two patients who had gross residual
disease after surgery, and one patient with both microscopic positive margin and
a positive lymph node (the only patient to undergo lymph node sampling). There
was no severe acute morbidity and only one patient had severe late morbidity.
CONCLUSIONS: Invasive carcinoma found after simple hysterectomy may be treated
safely and effectively with postoperative radiotherapy. Patients with known
residual disease following surgery do poorly with either radiotherapy or
reoperation, but treatment with radiotherapy alone may be less morbid. Also, for
the treatment of minimal disease external beam radiation to the pelvis appears to
be as effective and possibly less morbid than radical reoperation.
PMID- 10192355
TI - Iridium-192 transperineal interstitial brachytherapy for locally advanced or
recurrent gynecological malignancies.
AB - PURPOSE: To assess treatment outcome for patients with locally advanced or
recurrent gynecological malignancies treated with continuous low-dose-rate (LDR)
remote afterloading brachytherapy using the Martinez Universal Perineal
Interstitial Template (MUPIT). MATERIALS AND METHODS: Between 7/85 and 6/94, 69
patients with either locally advanced or recurrent malignancies of the cervix,
endometrium, vagina, or female urethra were treated by 5 different physicians
using the MUPIT with (24 patients) or without (45 patients) interstitial
hyperthermia. Fifty-four patients had no prior treatment with radiation and
received a combination of external beam irradiation (EBRT) and an interstitial
implant. The combined median dose was 71 Gy (range 56-99 Gy), median EBRT dose
was 39 Gy (range 30-74 Gy), and the median implant dose was 32 Gy (range 17-40
Gy). Fifteen patients with prior radiation treatment received an implant alone.
The total median dose including previous EBRT was 91 Gy (range 70-130 Gy) and the
median implant dose was 35 Gy (range 25-55 Gy). RESULTS: With a median follow-up
of 4.7 yr in survivors, the 3-yr actuarial local control (LC), disease-specific
survival (DSS), and overall survival (OS) for all patients was 60%, 55%, and 41%
respectively. The clinical complete response rate was 78% and in these patients
the 3-year actuarial LC, DSS, and OS was 78%, 79%, and 63% respectively. On
univariate analysis for local control, disease volume and hemoglobin were found
to be statistically significant. On multivariate analysis, however, only disease
volume remained significant (p = 0.011). There was no statistically significant
difference in local control whether patients had received any prior treatment
with radiation (p = 0.34), had recurrent disease (p = 0.13), or which physician
performed the implant (p = 0.45). The grade 4 complication rate (small bowel
obstruction requiring surgery, fistulas, soft tissue necrosis) for all patients
was 14%. With a dose rate less than 70 cGy/hour, the grade 4 complication rate
was 3% vs. 24% with dose rate > or = 70 cGy/hour (p = 0.013). CONCLUSION:
Patients with locally advanced or recurrent gynecological malignancies treated
with the remote afterloader LDR MUPIT applicator can expect reasonable rates of
local control that are not operator-dependent. Complication rates with this
approach are acceptable and appear to be related to the dose rate.
PMID- 10192356
TI - Medium-dose-rate brachytherapy of cancer of the cervix: preliminary results of a
prospectively designed schedule based on the linear-quadratic model.
AB - PURPOSE: To compare results and complications of our previous low-dose-rate (LDR)
brachytherapy schedule for early-stage cancer of the cervix, with a prospectively
designed medium-dose-rate (MDR) schedule, based on the linear-quadratic model
(LQ). METHODS AND MATERIALS: A combination of brachytherapy, external beam pelvic
and parametrial irradiation was used in 102 consecutive Stage Ib-IIb LDR treated
patients (1986-1990) and 42 equally staged MDR treated patients (1994-1996). The
planned MDR schedule consisted of three insertions on three treatment days with
six 8-Gy brachytherapy fractions to Point A, two on each treatment day with an
interfraction interval of 6 hours, plus 18 Gy external whole pelvic dose, and
followed by additional parametrial irradiation. The calculated biologically
effective dose (BED) for tumor was 90 Gy10 and for rectum below 125 Gy3. RESULTS:
In practice the MDR brachytherapy schedule achieved a tumor BED of 86 Gy10 and a
rectal BED of 101 Gy3. The latter was better than originally planned due to a
reduction from 85% to 77% in the percentage of the mean dose to the rectum in
relation to Point A. The mean overall treatment time was 10 days shorter for MDR
in comparison with LDR. The 3-year actuarial central control for LDR and MDR was
97% and 98% (p = NS), respectively. The Grades 2 and 3 late complications (scale
0 to 3) were 1% and 2.4%, respectively for LDR (3-year) and MDR (2-year).
CONCLUSIONS: LQ is a reliable tool for designing new schedules with altered
fractionation and dose rates. The MDR schedule has proven to be an equivalent
treatment schedule compared with LDR, with an additional advantage of having a
shorter overall treatment time. The mean rectal BED Gy3 was lower than expected.
PMID- 10192357
TI - Radiation therapy in the treatment of giant cell tumor of bone.
AB - PURPOSE: To assess the local control rate and potential complications of
radiotherapy, and the factors influencing response to radiotherapy for primary
and locally recurrent giant cell tumor of bone. METHODS AND MATERIALS: Twenty
patients were irradiated for giant cell tumor of bone between 1983 and 1993.
Fourteen patients received radiotherapy at the time of primary diagnosis (10 had
biopsy and 4 partial surgery) and 6 patients at the time of local recurrence
(following additional surgery in 2). Fourteen patients had tumors of the
extremity and six of the vertebral column. The radiotherapy dose ranged from 40
60 Gy in 15-30 fractions over 3-6 weeks. The response to radiotherapy was
assessed by clinical and radiological criteria and the probable factors
influencing response were analyzed. RESULTS: The median follow-up period was 48
months (range, 4 months to 13 years). Local control was obtained in 18/20
patients. The two local failures were salvaged, one by reirradiation and the
other by surgery. Only one patient died of giant cell tumor, following extensive
bone marrow infiltration. There was no serious late toxicity or malignant
transformation. The response to radiotherapy was not influenced by disease status
at presentation, tumor site, radiotherapy schedule, or presence of soft tissue
extension. CONCLUSIONS: Radiotherapy is effective in producing local control in
primary as well as recurrent giant cell tumor of bone. There are no major
complications and no significant risk of malignant transformation. Radiotherapy
could be considered as the primary treatment modality in patients where surgery
would produce functional deficits.
PMID- 10192358
TI - A simple technique for treating age-related macular degeneration with external
beam radiotherapy.
AB - PURPOSE: To develop a simple external beam photon radiotherapy technique to treat
age-related macular degeneration without the need for simulation, planning
computed tomography (CT) or computer dosimetry. METHODS AND MATERIALS: The goal
was to enable the treatment to be set up reliably on the treatment machine on Day
1 with the patient supine in a head cast without any prior planning. Using
measurements of ocular globe topography from Karlsson et al. (Int J Radiat Oncol
Biol Phys 1996; 33: 705-712), we chose a point 1.5 cm behind the anterior surface
of the upper eyelid (ASUE) as the isocentre of a half-beam, blocked, 5.0 x 3.0
cm, angled lateral field to treat the involved eye. This would position the
isocentre about 0.5 cm behind the posterior surface of the lens, and a little
over 1 cm in front of the macula, according to Karlsson et al. The setup requires
initial adjustment of the gantry from horizontal (to account for any asymmetry of
position of the eyes), then angling 15 degrees posteriorly to avoid the
contralateral eye. Finally, the couch is raised to position the isocentre 1.5 cm
behind the ASUE. RESULTS: To verify the applicability of the technique, we
performed CT and computer dosimetry on the first 11 eyes so treated. Our CT
measurements were in good agreement with Karlsson et al. The lens dose was < 5%
and the macula was within the 95% isodose curve in each case (6-MV linac).
Treatment setup time is approximately 10 min each day. The 11 patients were
treated with 5 x 2.00 Gy (2 patients) or 5 x 3.00 Gy (9 patients), and subjective
response on follow-up over 1 to 12 months (median 4 months) was comparable to
previously reported results, with no significant acute side effects. CONCLUSION:
Our technique is easy to set up and reliably treats the macula, with sparing of
the lens and contralateral eye. It enables treatment to commence rapidly and cost
effectively without the need for simulation or CT computer planning.
PMID- 10192359
TI - The employment status of 1995 graduates from radiation oncology training programs
in the United States.
AB - PURPOSE: To quantify the employment status of 1995 graduates of radiation
oncology training programs in the United States. METHODS AND MATERIALS: All
senior residents (149) and fellows (36) who completed training in 1995 were
mailed an employment survey questionnaire by the Association of Residents in
Radiation Oncology (ARRO). Telephone follow-up of nonrespondents achieved a 100%
response rate. Twenty graduates who chose to continue training and five who
returned to their home countries were removed from the study. Of the 160 who
attempted to enter the U.S. workforce, 106 were men and 54 were women. Initial
job status and job status at 6-8 months following graduation were determined.
RESULTS: Unemployment was 6.9% at graduation and 4.4% at 6-8 months.
Underemployment (part-time employment) was 10.6% at graduation and 11.9% at 6-8
months postgraduation. Of those working part-time 6-8 months after graduation,
63% (12 of 19) did so involuntarily after unsuccessfully seeking full-time
employment. For the 20 graduates who chose to continue training with fellowships,
seven (35%) did so solely to avoid unemployment, four (20%) were partially
influenced by the job market, and nine (45%) were not influenced by the job
market. Adverse employment search outcome was defined as being either unemployed
as a radiation oncologist or involuntarily working part-time. Excluding those who
chose to work part-time, a total of 19 (11.9%) graduates at 6-8 months following
graduation, compared to 22 (13.8%) at graduation, were either unemployed or
involuntarily working part-time. In terms of gender, this represented 18.5% (10
of 54) of females and 8.6% (9 of 105) of males. In terms of geographic
restrictions in the job search, 56% of males and 70% of females with an adverse
employment outcome limited their job search to certain parts of the country. This
compares to 62% of all graduates in this study with geographic restrictions in
their job search. In terms of perceptions of the workforce and employment
opportunities, 95% of all graduates believed there was an oversupply of radiation
oncologists and 95.5% believed the job market was worse than what they had
anticipated on entering training. Only 42.8% of all graduates were satisfied with
the job opportunities available to them. A significant number of private practice
positions (41%) did not offer a partnership track, and those that did so had an
increased median employment period before partnership (3.25 years) compared to
previous years. CONCLUSION: This is the only employment survey for any specialty
in which a 100% response rate was achieved. Upon graduation, a significant number
of residents and fellows were either unemployed or involuntarily underemployed.
The job market absorbed only a fraction of them at 6-8 months. Most graduates,
including those employed full-time, were not satisfied with the practice
opportunities available to them during their job search. Many private-sector jobs
did not offer a partnership track, and those that did required an increased
employment period. A higher rate of involuntary part-time employment was seen for
female graduates. Geographic restrictions in job search alone could not account
for graduates being unemployed or underemployed, and could not account for gender
differences. An overwhelming majority of 1995 radiation oncology graduates
believed that the job market had deteriorated and that there was an oversupply of
radiation oncologists. As one of two major studies tracking the employment status
of radiation oncology graduates, we believe this study to be superior in
methodology. We also believe this study presents data in a manner useful to
medical students, training program directors, and healthcare policymakers.
PMID- 10192360
TI - Superfractionation as a potential hypoxic cell radiosensitizer: prediction of an
optimum dose per fraction.
AB - PURPOSE: A dose "window of opportunity" has been identified in an earlier
modeling study (1) if the inducible repair variant of the LQ model is adopted
instead of the pure LQ model, and if all survival curve parameters are equally
modified by the presence or absence of oxygen. In this paper we have extended the
calculations to consider survival curve parameters from 15 sets of data obtained
for cells tested at low doses using clonogenic assays. METHODS AND MATERIALS: A
simple computer model has been used to simulate the response of each cell line to
various doses per fraction in multifraction schedules, with oxic and hypoxic
cells receiving the same fractional dose. We have then used pairs of simulated
survival curves to estimate the effective hypoxic protection (OER') as a function
of the dose per fraction. RESULTS: The resistance of hypoxic cells is reduced by
using smaller doses per fraction than 2 Gy in all these fractionated clinical
simulations, whether using a simple LQ model, or the more complex LQ/IR model. If
there is no inducible repair, the optimum dose is infinitely low. If there is
inducible repair, there is an optimum dose per fraction at which hypoxic
protection is minimized. This is usually around 0.5 Gy. It depends on the dose
needed to induce repair being higher in hypoxia than in oxygen. The OER' may even
go below unity, i.e. hypoxic cells may be more sensitive than oxic cells.
CONCLUSIONS: If oxic and hypoxic cells are repeatedly exposed to doses of the
same magnitude, as occurs in clinical radiotherapy, the observed hypoxic
protection varies with the fractional dose. The OER' is predicted to diminish at
lower doses in all cell lines. The loss of hypoxic resistance with
superfractionation is predicted to be proportional to the capacity of the cells
to induce repair, i.e. their intrinsic radioresistance at a dose of 2 Gy.
PMID- 10192361
TI - Fractionation and protraction for radiotherapy of prostate carcinoma.
AB - PURPOSE: To investigate whether current fractionation and brachytherapy
protraction schemes for the treatment of prostatic cancer with radiation are
optimal, or could be improved. METHODS AND MATERIALS: We analyzed two mature data
sets on radiotherapeutic tumor control for prostate cancer, one using EBRT and
the other permanent seed implants, to extract the sensitivity to changes in
fractionation of prostatic tumors. The standard linear-quadratic model was used
for the analysis. RESULTS: Prostatic cancers appear significantly more sensitive
to changes in fractionation than most other cancers. The estimated alpha/beta
value is 1.5 Gy [0.8, 2.2]. This result is not too surprising as there is a
documented relationship between cellular proliferative status and sensitivity to
changes in fractionation, and prostatic tumors contain exceptionally low
proportions of proliferating cells. CONCLUSIONS: High dose rate (HDR)
brachytherapy would be a highly appropriate modality for treating prostate
cancer. Appropriately designed HDR brachytherapy regimens would be expected to be
as efficacious as low dose rate, but with added advantages of logistic
convenience and more reliable dose distributions. Similarly, external beam
treatments for prostate cancer can be designed using larger doses per fraction;
appropriately designed hypofractionation schemes would be expected to maintain
current levels of tumor control and late sequelae, but with reduced acute
morbidity, together with the logistic and financial advantages of fewer numbers
of fractions.
PMID- 10192362
TI - Effects of intraoperative irradiation (IORT) and intraoperative hyperthermia
(IOHT) on canine sciatic nerve: histopathological and morphometric studies.
AB - PURPOSE/OBJECTIVE: Peripheral neuropathies have emerged as the major dose
limiting complication reported after intraoperative radiation therapy (IORT). The
combination of IORT with hyperthermia may further increase the risk of peripheral
nerve injury. The objective of this study was to evaluate histopathological and
histomorphometric changes in the sciatic nerve of dogs, after IORT with or
without hyperthermia treatment. METHODS AND MATERIALS: Young adult beagle dogs
were randomized into five groups of 3-5 dogs each to receive IORT doses of 16,
20, 24, 28, or 32 Gy. Six groups of 4-5 dogs each received IORT doses of 12, 16,
20, 24, or 28 Gy simultaneously with 44 degrees C of intraoperative hyperthermia
(IOHT) for 60 min. One group of dogs acted as hyperthermia-alone controls. Two
years after the treatment, dogs were euthanized, and histopathological and
morphometric analyses were performed. RESULTS: Qualitative histological analysis
showed prominent changes such as focal necrosis, mineralization, fibrosis, and
severe fiber loss in dogs which received combined treatment. Histomorphometric
results showed a significantly higher decrease in axon and myelin and small blood
vessels, with a corresponding increase in connective tissue in dogs receiving
IORT plus hyperthermia treatment. The effective dose for 50% of nerve fiber loss
(ED50) in dogs exposed to IORT only was 25.3 Gy. The ED50 for nerve fiber loss in
dogs exposed to IORT combined with IOHT was 14.8 Gy. The thermal enhancement
ratio (TER) was 1.7. CONCLUSION: The probability of developing peripheral
neuropathies in a large animal model is higher when IORT is combined with IOHT,
when compared to IORT application alone. To minimize the risk of peripheral
neuropathy, clinical treatment protocols for the combination of IORT and
hyperthermia should not assume a thermal enhancement ratio (TER) to be lower than
1.5.
PMID- 10192363
TI - The relationship between elevated interstitial fluid pressure and blood flow in
tumors: a bioengineering analysis.
AB - PURPOSE: To examine the hypothesis that elevated interstitial fluid pressure
(IFP) is a cause of reduced blood flow in tumors. MATERIALS AND METHODS: A
physiologic model of tumor blood flow was developed based on a semipermeable,
compliant capillary in the center of a spherical tumor. The model incorporates
the interaction between the tumor vasculature and the interstitium, as mediated
by IFP. It also incorporates the dynamic behavior of the capillary wall in
response to changes in transmural pressure, and the effect of viscosity on blood
flow. RESULTS: The model predicted elevated tumor IFP in the range of 0 to 56
mmHg. The capillary diameter in the setting of elevated IFP was greatest at the
arterial end, and constricted to between 3.2 and 4.4 microm at the venous end.
This corresponded to a 2.4- to 3.5-fold reduction in diameter along the length of
the capillary. The IFP exceeded the intravascular pressure distally in the
capillary, but vascular collapse did not occur. Capillary diameter constriction
resulted in a 2.3- to 9.1-fold steady-state reduction in tumor blood flow
relative to a state of near-zero IFP. CONCLUSION: The results suggest that steady
state vascular constriction occurs in the setting of elevated IFP, and leads to
reduced tumor blood flow. This may in turn contribute to the development of
hypoxia, which is an important cause of radiation treatment failure in many
tumors.
PMID- 10192364
TI - Hematoporphyrin derivatives potentiate the radiosensitizing effects of 2-deoxy-D
glucose in cancer cells.
AB - PURPOSE: Two deoxy-D-glucose (2-DG), an inhibitor of glucose transport and
glycolysis, has been shown to differentially inhibit the repair of radiation
damage in cancer cells by reducing the flow of metabolic energy. Since
hematoporphyrin derivatives (Hpd) inhibit certain enzymes of the respiratory
metabolism, resulting in an increase in the glucose usage and glycolysis, Hpd
could possibly enhance the energy-linked radiosensitizing effects of 2-DG in
cancer cells. The purpose of the present work was to verify this suggestion.
METHODS AND MATERIALS: Two human tumor cell lines (cerebral glioma, BMG-1 and
squamous cell carcinoma, 4197) and a murine tumor cell line (Ehrlich ascites
tumor [EAT], F-15) in vitro were investigated. A commercially available
preparation of Hpd, Photosan-3 (PS-3) was used in the present studies. Cells
incubated with 0-10 microg/ml PS-3 for 0-24 h before irradiation were exposed to
2.5 Gy of Co-60 gamma rays and maintained under liquid holding conditions for 1-4
h to facilitate repair. 2-DG (0-5 mM) added at the time of irradiation was
present during the liquid holding. Radiation-induced cytogenetic damage
(micronuclei formation) and cell death (macrocolony assay) were analyzed as
parameters of radiation response. Effects of these radiosensitizers on glucose
usage and glycolysis were also studied by measuring the glucose consumption and
lactate production using enzymatic assays. RESULTS: The glucose consumption and
lactate production of BMG-1 cells (0.83 and 1.43 pmole/cell/h) were twofold
higher than in the 4197 cells (0.38 and 0.63 pmole/cell/h). Presence of PS-3 (10
microg/ml) enhanced the rate of glycolysis (glucose consumption and lactate
production) in these cells by 35% to 65%, which was reduced by 20% to 40% in the
presence of 5 mM 2-DG. In exponentially growing BMG-1 and EAT cells, presence of
2-DG (5 mM; equimolar with glucose) for 4 hours after irradiation increased the
radiation-induced micronuclei formation and cell death by nearly 40%, whereas no
significant effects could be observed in 4197 cells. In EAT cells, radiation was
also observed to induce apoptotic death, which was significantly increased in the
presence of the combination (PS-3 + 2-DG). The combination (PS-3 + 2-DG) enhanced
the radiation damage in all three cell systems by 60-100%. Furthermore, the
radiosensitizing effects of the combination (PS-3 + 2-DG) were higher at pH 6.7
as compared to pH 7. 4. In the plateau phase, presence of 2-DG alone did not
significantly influence the radiation response of either BMG-1 or of 4197 cells,
whereas in combination with PS-3, 2-DG enhanced the radiation damage in both
these cell lines by 40% to 50%. Furthermore, in BMG-1 cells, the effects of 2-DG
were observed to be reversible to a very great extent, while that of the
combination were mostly irreversible. CONCLUSION: The hematoporphyrin derivative
PS-3 enhances the radiosensitizing effects of 2-DG in cancer cells, possibly by
further reducing the energy supply leading to an irreversible inhibition of DNA
repair, and increased cytogenetic damage and cell death. Since both these
compounds have been used in clinical practice, further studies to investigate
their use in improving radiotherapy of tumors are warranted.
PMID- 10192365
TI - Image registration of BANG gel dose maps for quantitative dosimetry verification.
AB - BACKGROUND: The BANG (product symbol SGEL, MGS Research Inc., Guilford, CT)
polymer gel has been shown to be a valuable dosimeter for determining three
dimensional (3D) dose distributions. Because the proton relaxation rate (R2) of
the gel changes as a function of absorbed dose, MR scans of the irradiated gel
can be used to generate 3D dose maps. Previous work with the gel, however, has
not relied on precise localization of the measured dose distribution. This has
limited its quantitative use, as no precise correlation exists with the planned
distribution. This paper reports on a technique for providing this correlation,
thus providing a quality assurance tool that includes all of the steps of
imaging, treatment planning, dose calculation, and treatment localization.
METHODS AND MATERIALS: The BANG gel formulation was prepared and poured into
spherical flasks (15.3-cm inner diameter). A stereotactic head ring was attached
to each flask. Three magnetic resonance imaging (MRI) and computed tomography
(CT) compatible fiducial markers were placed on the flask, thus defining the
central axial plane. A high-resolution CT scan was obtained of each flask. These
images were transferred to a radiosurgery treatment-planning program, where
treatment plans were developed. The gels were irradiated using our systems for
stereotactic radiosurgery or fractionated stereotactic radiotherapy. The gels
were MR imaged, and a relative 3D dose map was created from an R2 map of these
images. The dose maps were transferred to an image-correlation program, and then
fused to the treatment-planning CT scan through a rigid body match of the MRI/CT
compatible fiducial markers. The fused dose maps were imported into the treatment
planning system for quantitative comparison with the calculated treatment plans.
RESULTS: Calculated and measured isodose surfaces agreed to within 2 mm at the
worst points within the in-plane dose distributions. This agreement is excellent,
considering that the pixel resolution of the MRI dose maps is 1.56 x 1.56 mm, and
the treatment-planning dose distributions were calculated on a 1-mm dose grid.
All points within the dose distribution were well within the tolerances set forth
for commissioning and quality assurance of stereotactic treatment-planning
systems. Moreover, the quantitative evaluation presented here tests the accuracy
of the entire treatment-planning and delivery process, including stereotactic
frame rigidity, CT localization, CT/MR correlation, dose calculation, and
radiation delivery. CONCLUSION: BANG polymer gel dosimetry coupled with image
correlation provides quantitative verification of the accuracy of 3D dose
distributions. Such quantitative evaluation is imperative to ensure the high
quality of the 3D dose distributions generated and delivered by stereotactic and
other conformal irradiation systems.
PMID- 10192366
TI - Treatment plan evaluation using dose-volume histogram (DVH) and spatial dose
volume histogram (zDVH).
AB - OBJECTIVE: The dose-volume histogram (DVH) has been accepted as a tool for
treatment-plan evaluation. However, DVH lacks spatial information. A new concept,
the z-dependent dose-volume histogram (zDVH), is presented as a supplement to the
DVH in three-dimensional (3D) treatment planning to provide the spatial
variation, as well as the size and magnitude of the different dose regions within
a region of interest. MATERIALS AND METHODS: Three-dimensional dose calculations
were carried out with various plans for three disease sites: lung, breast, and
prostate. DVHs were calculated for the entire volume. A zDVH is defined as a
differential dose-volume histogram with respect to a computed tomographic (CT)
slice position. In this study, zDVHs were calculated for each CT slice in the
treatment field. DVHs and zDVHs were compared. RESULTS: In the irradiation of
lung, DVH calculation indicated that the treatment plan satisfied the dose-volume
constraint placed on the lung and zDVH of the lung revealed that a sizable
fraction of the lung centered about the central axis (CAX) received a significant
dose, a situation that warranted a modification of the treatment plan due to the
removal of one lung. In the irradiation of breast with tangential fields, the DVH
showed that about 7% of the breast volume received at least 110% of the
prescribed dose (PD) and about 11% of the breast received less than 98% PD.
However, the zDVHs of the breast volume in each of seven planes showed the
existence of high-dose regions of 34% and 15%, respectively, of the volume in the
two caudal-most planes and cold spots of about 40% in the two cephalic planes. In
the treatment planning of prostate, DVHs showed that about 15% of the bladder and
40% of the rectum received 102% PD, whereas about 30% of the bladder and 50% of
the rectum received the full dose. Taking into account the hollow structure of
both the bladder and the rectum, the dose-surface histograms (DSH) showed larger
hot-spot volume, about 37% of the bladder wall and 43% of the rectal wall. The
zDVHs of the bladder revealed that the hot-spot region was superior to the
central axis. The zDVHs of the rectum showed that the high-dose region was an 8
cm segment mostly superior to the central axis. The serial array-like of the
rectum warrants a closer attention with regard to the complication probability of
the organ. CONCLUSIONS: Although DVH provides an averaged dose-volume
information, zDVH provides differential dose-volume information with respect to
the CT slice position. zDVH is a 2D analog of a 3D DVH and, in some situations,
more superior. It provides additional information on plan evaluation that
otherwise could not be appreciated. The zDVH may be used along with DVH for plan
evaluation and for the correlation of radiation outcome.
PMID- 10192367
TI - Beam collimation and bolusing material optimizations for 10boron neutron capture
enhancement of fast neutron (BNCEFN): definition of the optimum irradiation
technique.
AB - PURPOSE: In boron-10 neutron capture enhancement of fast neutron irradiation
(BNCEFN), the dose enhancement is correlated to the 10B concentration and thermal
neutron flux. A new irradiation technique is presented to optimize the thermal
neutron flux. METHODS AND MATERIALS: The coupled FLUKA and MCNP-4A Monte Carlo
codes were used to simulate the neutron production and transport for the Nice and
Orleans facilities. RESULTS: The new irradiation technique consists of a 20-cm
lead blocks additional collimator, placed close to the patient's head, which is
embedded in a pure graphite cube. A 24-fold thermal neutron flux increase is
calculated between a 5 x 5 cm2 primary collimated field, with the patient's head
in the air, and the same field size irradiated with the optimum irradiation
technique. This increase is more important for the p(60)+Be Nice beam than for
the p(34)+Be Orleans one. The thermal neutron flux is 2.1 x 10(10) n(th)/Gy for
each facility. Assuming a 100 microg/g 10B concentration, a physical dose
enhancement of 22% is calculated. Moreover, the thermal neutron flux becomes
independent of the field size and the phantom head size. CONCLUSION: This
technique allows conformal irradiation of the tumor bed, while the thermal
neutron flux is enhanced, and spreads far around the tumor.
PMID- 10192368
TI - Dosimetry of hip irradiation for the prevention of heterotopic bone formation
after arthroplasty.
AB - PURPOSE: The dosimetry of hip irradiation for the prevention of heterotopic bone
formation following arthroplasty is complicated by the use of custom shielding in
the treatment portal, and the fact that irradiation is usually required during a
48 hour period following surgery. Both the machine output and depth dose factors
of the resulting fields are modified by the presence of the shielding blocks. A
simplified dosimetric approach, based on correction factors for both the output
and depth dose as a function of field geometry is presented for various
megavoltage energy beams. MATERIALS AND METHODS: Measurements of relative dose
factors (RDF) and percentage depth dose (PDD) were carried out for different
combinations of field size, block size and separation between adjacent blocks.
Both RDF and PDD measurements were made in a water phantom. Ratios of RDF and PDD
were obtained by dividing individual measurements or curves by the corresponding
values for the open field (i.e., without blocks). The average values of these
ratios constitute the correction factors to be applied for a given MU or
treatment time calculation. RESULTS: Extensive RDF and PDD measurements reveal
that for the field and block dimensions of interest the correction factors for
RDF can be parameterized as a function of separation between two adjacent blocks
and beam energy alone and the depth correction factors are additionally only a
function of depth. The correction factors for depth dose are equally valid for
fixed source-skin distance techniques (that use PDD) and fixed source-axis
distance techniques (that use TMR). CONCLUSION: A simple model for the
calculation of output in hip irradiation is presented for the situation where the
use of computer-based algorithms may not be practical. The model accurately
predicts the RDF of the treatment portal to within 2% and the PDD to within 2%
for the range of field sizes, block sizes, block gaps and beam energies of
interest ignoring other variables.
PMID- 10192369
TI - Regarding, Teo, Kwan, Chan et al., IJROBP 40:897-913; 1998.
PMID- 10192370
TI - Results from the Collaborative Ocular Melanoma Study (COMS) of enucleation versus
preoperative radiation therapy in the management of large ocular melanomas.
PMID- 10192371
TI - Regarding IJROBP 40:1111-1116, 1998, and IJROBP 40:1237-1242, 1998.
PMID- 10192372
TI - Regarding prognostic factors derived from recursive partition analysis (RPA) of
Radiation Therapy Oncology Group (RTOG) brain metastases trials applied to
surgically resected and irradiated brain metastatic cases: Agboola et al., IJROBP
42:155-159; 1998.
PMID- 10192373
TI - Regarding Peters, IJROBP 1998;40:527-528, and Lundahl, Foote, Bonner, et al.,
IJROBP 1998;40:529-534.
PMID- 10192374
TI - Publishing paradigms.
PMID- 10192375
TI - Anti-Xistentialism.
PMID- 10192376
TI - Mediating immunity to mycobacteria.
PMID- 10192377
TI - A vital role for vitamin A.
PMID- 10192378
TI - Making sense out of sound.
PMID- 10192379
TI - A common nonsense mutation results in alpha-actinin-3 deficiency in the general
population.
PMID- 10192380
TI - A mutation in NRL is associated with autosomal dominant retinitis pigmentosa.
PMID- 10192381
TI - Counting the repetitive kringle-IV repeats in the gene encoding human
apolipoprotein(a) by fibre-FISH.
PMID- 10192382
TI - Atm haploinsufficiency results in increased sensitivity to sublethal doses of
ionizing radiation in mice.
PMID- 10192383
TI - Loss of information due to ambiguous haplotyping of SNPs.
PMID- 10192384
TI - Genetic determinism and the overprotection of human subjects.
PMID- 10192385
TI - A mutation in OTOF, encoding otoferlin, a FER-1-like protein, causes DFNB9, a
nonsyndromic form of deafness.
AB - Using a candidate gene approach, we identified a novel human gene, OTOF,
underlying an autosomal recessive, nonsyndromic prelingual deafness, DFNB9. The
same nonsense mutation was detected in four unrelated affected families of
Lebanese origin. OTOF is the second member of a mammalian gene family related to
Caenorhabditis elegans fer-1. It encodes a predicted cytosolic protein (of 1,230
aa) with three C2 domains and a single carboxy-terminal transmembrane domain. The
sequence homologies and predicted structure of otoferlin, the protein encoded by
OTOF, suggest its involvement in vesicle membrane fusion. In the inner ear, the
expression of the orthologous mouse gene, mainly in the sensory hair cells,
indicates that such a role could apply to synaptic vesicles.
PMID- 10192386
TI - A human IFNGR1 small deletion hotspot associated with dominant susceptibility to
mycobacterial infection.
AB - The immunogenetic basis of severe infections caused by bacille Calmette-Guerin
vaccine and environmental mycobacteria in humans remains largely unknown. We
describe 18 patients from several generations of 12 unrelated families who were
heterozygous for 1 to 5 overlapping IFNGR1 frameshift small deletions and a wild
type IFNGR1 allele. There were 12 independent mutation events at a single
mutation site, defining a small deletion hotspot. Neighbouring sequence analysis
favours a small deletion model of slipped mispairing events during replication.
The mutant alleles encode cell-surface IFNgamma receptors that lack the intra
cytoplasmic domain, which, through a combination of impaired recycling, abrogated
signalling and normal binding to IFNgamma exert a dominant-negative effect. We
thus report a hotspot for human IFNGR1 small deletions that confer dominant
susceptibility to infections caused by poorly virulent mycobacteria.
PMID- 10192387
TI - An untranslated CTG expansion causes a novel form of spinocerebellar ataxia
(SCA8)
AB - Myotonic dystrophy (DM) is the only disease reported to be caused by a CTG
expansion. We now report that a non-coding CTG expansion causes a novel form of
spinocerebellar ataxia (SCA8). This expansion, located on chromosome 13q21, was
isolated directly from the genomic DNA of an ataxia patient by RAPID cloning.
SCA8 patients have expansions similar in size (107-127 CTG repeats) to those
found among adult-onset DM patients. SCA8 is the first example of a dominant SCA
not caused by a CAG expansion translated as a polyglutamine tract.
PMID- 10192388
TI - Comparative genomes of Chlamydia pneumoniae and C. trachomatis.
AB - Chlamydia are obligate intracellular eubacteria that are phylogenetically
separated from other bacterial divisions. C. trachomatis and C. pneumoniae are
both pathogens of humans but differ in their tissue tropism and spectrum of
diseases. C. pneumoniae is a newly recognized species of Chlamydia that is a
natural pathogen of humans, and causes pneumonia and bronchitis. In the United
States, approximately 10% of pneumonia cases and 5% of bronchitis cases are
attributed to C. pneumoniae infection. Chronic disease may result following
respiratory-acquired infection, such as reactive airway disease, adult-onset
asthma and potentially lung cancer. In addition, C. pneumoniae infection has been
associated with atherosclerosis. C. trachomatis infection causes trachoma, an
ocular infection that leads to blindness, and sexually transmitted diseases such
as pelvic inflammatory disease, chronic pelvic pain, ectopic pregnancy and
epididymitis. Although relatively little is known about C. trachomatis biology,
even less is known concerning C. pneumoniae. Comparison of the C. pneumoniae
genome with the C. trachomatis genome will provide an understanding of the common
biological processes required for infection and survival in mammalian cells.
Genomic differences are implicated in the unique properties that differentiate
the two species in disease spectrum. Analysis of the 1,230,230-nt C. pneumoniae
genome revealed 214 protein-coding sequences not found in C. trachomatis, most
without homologues to other known sequences. Prominent comparative findings
include expansion of a novel family of 21 sequence-variant outer-membrane
proteins, conservation of a type-III secretion virulence system, three
serine/threonine protein kinases and a pair of parologous phospholipase-D-like
proteins, additional purine and biotin biosynthetic capability, a homologue for
aromatic amino acid (tryptophan) hydroxylase and the loss of tryptophan
biosynthesis genes.
PMID- 10192389
TI - Independent regulation of the two Pax5 alleles during B-cell development.
AB - The developmental control genes of the Pax family are frequently associated with
mouse mutants and human disease syndromes. The function of these transcription
factors is sensitive to gene dosage, as mutation of one allele or a modest
increase in gene number results in phenotypic abnormalities. Pax5 has an
important role in B-cell and midbrain development. By following the expression of
individual Pax5 alleles at the single-cell level, we demonstrate here that Pax5
is subject to allele-specific regulation during B-lymphopoiesis. Pax5 is
predominantly transcribed from only one allele in early progenitors and mature B
cells, whereas it switches to a biallelic transcription mode in immature B cells.
The allele-specific regulation of Pax5 is stochastic, reversible, independent of
parental origin and correlates with synchronous replication, in contrast with
imprinted and other monoallelically expressed genes. As a consequence, B-lymphoid
tissues are mosaics with respect to the transcribed Pax5 allele, and thus
mutation of one allele in heterozygous mice results in deletion of the cell
population expressing the mutant allele due to loss of Pax5 function at the
single-cell level. Similar allele-specific regulation may be a common mechanism
causing the haploinsufficiency and frequent association of other Pax genes with
human disease.
PMID- 10192390
TI - Transferrin receptor is necessary for development of erythrocytes and the nervous
system.
AB - Plasma iron circulates bound to transferrin (Trf), which solubilizes the ferric
ion and attenuates its reactivity. Diferric Trf interacts with cell-surface Trf
receptor (Trfr) to undergo receptor-mediated endocytosis into specialized
endosomes. Endosomal acidification leads to iron release, and iron is transported
out of the endosome through the activity of divalent metal transporter 1 (DMT1,
formerly Nramp2), a transmembrane iron transporter that functions only at low pH.
Trf and Trfr then return to the cell surface for reuse, completing a highly
efficient cycle. Although the Trf cycle is assumed to be the general mechanism
for cellular iron uptake, this has not been validated experimentally. Mice with
hypotransferrinaemia (hpx) have little or no plasma Trf. They have severe
anaemia, indicating that the Trf cycle is essential for iron uptake by erythroid
cells. Other hpx tissues, however, are generally normal, and there is a
paradoxical increase in intestinal iron absorption and iron storage. To test the
hypothesis that the Trf cycle has unique importance for erythropoiesis, we
disrupted the Trfr gene in mice. This results in elimination of the Trf cycle,
but leaves other Trf functions intact. Mice lacking Trfr have a more severe
phenotype than hpx mice, affecting both erythropoiesis and neurologic
development. Furthermore, haploinsufficiency for Trfr results in impaired
erythroid development and abnormal iron homeostasis.
PMID- 10192391
TI - Tsix, a gene antisense to Xist at the X-inactivation centre.
AB - In mammals, dosage compensation is achieved by X inactivation and is regulated in
cis by the X-inactivation centre (Xic) and Xist. The Xic controls X-chromosome
counting, choice of X to inactivate and initiation of silencing. Xic action
culminates in a change in Xist RNA property from a scarce, unstable RNA to highly
expressed Xist RNA that coats the future inactive X. Deleting a 65-kb region
downstream of Xist results in constitutive Xist expression and X inactivation,
implying the presence of a cis-regulatory element. In this region, we now report
the discovery of a gene antisense to Xist. Tsix is a 40-kb RNA originating 15 kb
downstream of Xist and transcribed across the Xist locus. Tsix sequence is
conserved at the human XIC. Tsix RNA has no conserved ORFs, is seen exclusively
in the nucleus and is localized at Xic. Before the onset of X inactivation, Tsix
is expressed from both X chromosomes. At the onset of X inactivation, Tsix
expression becomes monoallelic, is associated with the future active X and
persists until Xist is turned off. Tsix is not found on the inactive X once cells
enter the X-inactivation pathway. Tsix has features suggesting a role in
regulating the early steps of X inactivation, but not the silencing step.
PMID- 10192392
TI - Interacting loci cause severe iris atrophy and glaucoma in DBA/2J mice.
AB - Glaucomas are a major cause of blindness. Visual loss typically involves retinal
ganglion cell death and optic nerve atrophy subsequent to a pathologic elevation
of intraocular pressure (IOP). Some human glaucomas are associated with anterior
segment abnormalities such as pigment dispersion syndrome (PDS) and iris atrophy
with associated synechiae. The primary causes of these abnormalities are unknown,
and their aetiology is poorly understood. We recently characterized a mouse
strain (DBA/2J) that develops glaucoma subsequent to anterior segment changes
including pigment dispersion and iris atrophy. Using crosses between mouse
strains DBA/2J (D2) and C57BL/6J (B6), we now show there are two chromosomal
regions that contribute to the anterior segment changes and glaucoma. Progeny
homozygous for the D2 allele of one locus on chromosome 6 (called ipd) develop an
iris pigment dispersion phenotype similar to human PDS. ipd resides on a region
of mouse chromosome 6 with conserved synteny to a region of human chromosome 7q
that is associated with human PDS. Progeny homozygous for the D2 allele of a
different locus on chromosome 4 (called isa) develop an iris stromal atrophy
phenotype (ISA). The Tyrpl gene is a candidate for isa and likely causes ISA via
a mechanism involving pigment production. Progeny homozygous for the D2 alleles
of both ipd and isa develop an earlier onset and more severe disease involving
pigment dispersion and iris stromal atrophy.
PMID- 10192393
TI - A common human skin tumour is caused by activating mutations in beta-catenin.
AB - WNT signalling orchestrates a number of developmental programs. In response to
this stimulus, cytoplasmic beta-catenin (encoded by CTNNB1) is stabilized,
enabling downstream transcriptional activation by members of the LEF/TCF family.
One of the target genes for beta-catenin/TCF encodes c-MYC, explaining why
constitutive activation of the WNT pathway can lead to cancer, particularly in
the colon. Most colon cancers arise from mutations in the gene encoding
adenomatous polyposis coli (APC), a protein required for ubiquitin-mediated
degradation of beta-catenin, but a small percentage of colon and some other
cancers harbour beta-catenin-stabilizing mutations. Recently, we discovered that
transgenic mice expressing an activated beta-catenin are predisposed to
developing skin tumours resembling pilomatricomas. Given that the skin of these
adult mice also exhibits signs of de novo hair-follicle morphogenesis, we
wondered whether human pilomatricomas might originate from hair matrix cells and
whether they might possess beta-catenin-stabilizing mutations. Here, we explore
the cell origin and aetiology of this common human skin tumour. We found nuclear
LEF-1 in the dividing tumour cells, providing biochemical evidence that
pilomatricomas are derived from hair matrix cells. At least 75% of these tumours
possess mutations affecting the amino-terminal segment, normally involved in
phosphorylation-dependent, ubiquitin-mediated degradation of the protein. This
percentage of CTNNB1 mutations is greater than in all other human tumours
examined thus far, and directly implicates beta-catenin/LEF misregulation as the
major cause of hair matrix cell tumorigenesis in humans.
PMID- 10192394
TI - The complete family of genes encoding G proteins of Caenorhabditis elegans.
AB - Caenorhabditis elegans is the first animal whose genomic sequence has been
determined. One of the new possibilities in post-sequence genetics is the
analysis of complete gene families at once. We studied the family of
heterotrimeric G proteins. C. elegans has 20 Galpha, 2 Gbeta and 2 Ggamma genes.
There is 1 homologue of each of the 4 mammalian classes of Galpha genes,
G(i)/G(o)alpha, G(s)alpha , G(q)alpha and G12alpha, and there are 16 new alpha
genes. Although the conserved Galpha subunits are expressed in many neurons and
muscle cells, GFP fusions indicate that 14 new Galpha genes are expressed almost
exclusively in a small subset of the chemosensory neurons of C. elegans. We
generated loss-of-function alleles using target-selected gene inactivation. None
of the amphid-expressed genes are essential for viability, and only four show any
detectable phenotype (chemotaxis defects), suggesting extensive functional
redundancy. On the basis of functional analysis, the 20 genes encoding Galpha
proteins can be divided into two groups: those that encode subunits affecting
muscle activity (homologues of G(i)/G(o)alpha, G(s)alpha and G(q)), and those (14
new genes) that encode proteins most likely involved in perception.
PMID- 10192395
TI - Identification of the gene responsible for gelatinous drop-like corneal
dystrophy.
AB - Gelatinous drop-like corneal dystrophy (GDLD; OMIM 204870) is an autosomal
recessive disorder characterized by severe corneal amyloidosis leading to
blindness, with an incidence of 1 in 300,000 in Japan. Our previous genetic
linkage study localized the gene responsible to a 2.6-cM interval on chromosome
1p. Clinical manifestations, which appear in the first decade of life, include
blurred vision, photophobia and foreign-body sensation. By the third decade,
raised, yellowish-grey, gelatinous masses severely impair visual acuity, and
lamellar keratoplasty is required for most patients. Here we report DNA
sequencing, cDNA cloning and mutational analyses of four deleterious mutations
(Q118X, 632delA, Q207X and S170X) in M1S1 (formerly TROP2 and GA733-1), encoding
a gastrointestinal tumour-associated antigen. The Q118X mutation was the most
common alteration in the GDLD patients examined, accounting for 33 of 40 (82.5%)
disease alleles in our panel of families. Protein expression analysis revealed
aggregation of the mutated, truncated protein in the perinuclear region, whereas
the normal protein was distributed diffusely in the cytoplasm with a homogenous
or fine granular pattern. Our successful identification of the gene that is
defective in GDLD should facilitate genetic diagnosis and potentially treatment
of the disease, and enhance general understanding of the mechanisms of
amyloidosis.
PMID- 10192396
TI - A novel endothelial-derived lipase that modulates HDL metabolism.
AB - High-density lipoprotein (HDL) cholesterol levels are inversely associated with
risk of atherosclerotic cardiovascular disease. At least 50% of the variation in
HDL cholesterol levels is genetically determined, but the genes responsible for
variation in HDL levels have not been fully elucidated. Lipoprotein lipase (LPL)
and hepatic lipase (HL), two members of the triacylglyerol (TG) lipase family,
both influence HDL metabolism and the HL (LIPC) locus has been associated with
variation in HDL cholesterol levels in humans. We describe here the cloning and
in vivo functional analysis of a new member of the TG lipase family. In contrast
to other family members, this new lipase is synthesized by endothelial cells in
vitro and thus has been termed endothelial lipase (encoded by the LIPG gene). EL
is expressed in vivo in organs including liver, lung, kidney and placenta, but
not in skeletal muscle. In contrast to LPL and HL, EL has a lid of only 19
residues. EL has substantial phospholipase activity, but less triglyceride lipase
activity. Overexpression of EL in mice reduced plasma concentrations of HDL
cholesterol and its major protein apolipoprotein A-I. The endothelial expression,
enzymatic profile and in vivo effects of EL suggest that it may have a role in
lipoprotein metabolism and vascular biology.
PMID- 10192397
TI - Retroposition of autosomal mRNA yielded testis-specific gene family on human Y
chromosome.
AB - Most genes in the human NRY (non-recombining portion of the Y chromosome) can be
assigned to one of two groups: X-homologous genes or testis-specific gene
families with no obvious X-chromosomal homologues. The CDY genes have been
localized to the human Y chromosome, and we report here that they are derivatives
of a conventional single-copy gene, CDYL (CDY-like), located on human chromosome
13 and mouse chromosome 6. CDY genes retain CDYL exonic sequences but lack its
introns. In mice, whose evolutionary lineage diverged before the appearance of
the Y-linked derivatives, the autosomal Cdyl gene produces two transcripts; one
is expressed ubiquitously and the other is expressed in testes only. In humans,
autosomal CDYL produces only the ubiquitous transcript; the testis-specific
transcript is the province of the Y-borne CDY genes. Our data indicate that CDY
genes arose during primate evolution by retroposition of a CDYL mRNA and
amplification of the retroposed gene. Retroposition contributed to the gene
content of the human Y chromosome, together with two other molecular evolutionary
processes: persistence of a subset of genes shared with the X chromosome and
transposition of genomic DNA harbouring intact transcription units.
PMID- 10192398
TI - The gene encoding proline dehydrogenase modulates sensorimotor gating in mice.
AB - Hemizygous cryptic deletions of the q11 band of human chromosome 22 have been
associated with a number of psychiatric and behavioural phenotypes, including
schizophrenia. Here we report the isolation and characterization of PRODH, a
human homologue of Drosophila melanogaster sluggish-A (slgA), which encodes
proline dehydrogenase responsible for the behavioural phenotype of the slgA
mutant. PRODH is localized at chromosome 22q11 in a region deleted in some
psychiatric patients. We also isolated the mouse homologue of slgA (Prodh),
identified a mutation in this gene in the Pro/Re hyperprolinaemic mouse strain
and found that these mice have a deficit in sensorimotor gating accompanied by
regional neurochemical alterations in the brain. Sensorimotor gating is a neural
filtering process that allows attention to be focused on a given stimulus, and is
affected in patients with neuropsychiatric disorders. Furthermore, several lines
of evidence suggest that proline may serve as a modulator of synaptic
transmission in the mammalian brain. Our observations, in conjunction with the
chromosomal location of PRODH, suggest a potential involvement of this gene in
the 22q11-associated psychiatric and behavioural phenotypes.
PMID- 10192399
TI - The Pendred syndrome gene encodes a chloride-iodide transport protein.
AB - Pendred syndrome is the most common form of syndromic deafness and characterized
by congenital sensorineural hearing loss and goitre. This disorder was mapped to
chromosome 7 and the gene causing Pendred syndrome (PDS) was subsequently
identified by positional cloning. PDS encodes a putative transmembrane protein
designated pendrin. Pendrin is closely related to a family of sulfate transport
proteins that includes the rat sulfate-anion transporter (encoded by Sat-1; 29%
amino acid sequence identity), the human diastrophic dysplasia sulfate
transporter (encoded by DTD; 32%) and the human sulfate transporter
'downregulated in adenoma' (encoded by DRA; 45%). On the basis of this homology
and the presence of a slightly modified sulfate-transporter signature sequence
comprising its putative second transmembrane domain, pendrin has been proposed to
function as a sulfate transporter. We were unable to detect evidence of sulfate
transport following the expression of pendrin in Xenopus laevis oocytes by
microinjection of PDS cRNA or in Sf9 cells following infection with PDS
recombinant baculovirus. The rates of transport for iodide and chloride were
significantly increased following the expression of pendrin in both cell systems.
Our results demonstrate that pendrin functions as a transporter of chloride and
iodide, but not sulfate, and may provide insight into thyroid physiology and the
pathophysiology of Pendred syndrome.
PMID- 10192400
TI - Embryonic retinoic acid synthesis is essential for early mouse post-implantation
development.
AB - A number of studies have suggested that the active derivative of vitamin A,
retinoic acid (RA), may be important for early development of mammalian embryos.
Severe vitamin A deprivation in rodents results in maternal infertility,
precluding a thorough investigation of the role of RA during embryogenesis. Here
we show that production of RA by the retinaldehyde dehydrogenase-2 (Raldh2)
enzyme is required for mouse embryo survival and early morphogenesis. Raldh2 is
an NAD-dependent aldehyde dehydrogenase with high substrate specificity for
retinaldehyde. Its pattern of expression during mouse development has suggested
that it may be responsible for embryonic RA synthesis. We generated a targeted
disruption of the mouse Raldh2 gene and found that Raldh2-/- embryos, which die
at midgestation without undergoing axial rotation (body turning), exhibit
shortening along the anterioposterior axis and do not form limb buds. Their heart
consists of a single, medial, dilated cavity. Their frontonasal region is
truncated and their otocysts are severely reduced. These defects result from a
block in embryonic RA synthesis, as shown by the lack of activity of RA
responsive transgenes, the altered expression of an RA-target homeobox gene and
the near full rescue of the mutant phenotype by maternal RA administration. Our
data establish that RA synthesized by the post-implantation mammalian embryo is
an essential developmental hormone whose lack leads to early embryo death.
PMID- 10192401
TI - Introduction: the use of mood stabilizers in the treatment of psychiatric
disorders.
PMID- 10192402
TI - Mood stabilizers and the evolution of maintenance study designs in bipolar I
disorder.
AB - The designs employed in bipolar maintenance studies have evolved greatly over the
last 28 years. Consequently, there has been minimal consensus set for methods
used to demonstrate the ability of any new putative mood stabilizers to prevent
relapse and recurrence in bipolar disorder. The methods that have evolved the
most include enrollment procedures, randomization schemes, use of outcome
measures, statistical analyses, and country-specific commercial and regulatory
issues. This article contrasts the various methods employed in first- and second
generation placebo-controlled bipolar I maintenance studies. This article also
explores the advantages and disadvantages associated with various designs.
PMID- 10192403
TI - An overview of the treatment of schizoaffective disorder.
AB - Schizoaffective disorder is a common, chronic, and frequently disabling
psychiatric disorder. However, its pharmacologic treatment has not been well
studied. The authors review studies of traditional and novel pharmacologic agents
in treatment of schizoaffective disorder, and based on the findings, present
preliminary pharmacologic treatment guidelines for the disorder.
PMID- 10192404
TI - Should we consider mood disturbance in schizophrenia as an important determinant
of quality of life?
AB - BACKGROUND: The main objective in the treatment of schizophrenia should be to
optimize individual patient functioning and quality of life. Little is known
about the possible relationship of concurrent mood symptoms and quality of life.
We hypothesized that the quality of life for people with schizophrenia would be
inversely related to the severity of concurrent mood disruption. METHOD: We
conducted a post hoc analysis of an international, multicenter, double-blind, 28
week study of 339 patients who met DSM-IV criteria for schizophrenia,
schizophreniform, or schizoaffective disorder and were randomized to treatment
with either olanzapine or risperidone. Quality of life data were collected at
baseline, 8, 16, 24, and 28 weeks or at early discontinuation; Positive and
Negative Syndrome Scale (PANSS) data were collected at each visit (weekly to week
8 and monthly thereafter). Correlations were calculated between changes in
quality of life (quality of life scale [QLS] total and subscales) and PANSS mood
score. Regression models were used to determine the proportion of variability in
the QLS total and subscores accounted for by changes in PANSS positive, PANSS
negative, and PANSS mood scores. Finally, path analysis was performed to
determine the mechanisms used by the PANSS mood scores to affect the QLS total
and subscores. RESULTS: Olanzapine demonstrated a significantly greater
therapeutic effect on the PANSS mood item than risperidone did. However, mood
improvements with either therapy demonstrated correlations of PANSS mood on the
QLS total and subscores which were statistically significant, with the strongest
correlation against the interpersonal relations (QLS-IPR) subscore. The path
analysis results indicate that the PANSS mood item's most significant path in
affecting the QLS total and QLS-IPR is direct. CONCLUSION: Changes in the quality
of life of schizophrenic patients is inversely related to changes in the
concurrent mood disruption. Early therapeutic interventions directed at a broader
constellation of schizophrenic symptomatology, including mood, may be helpful in
improving an individual patient's quality of life. The possible relative
advantages of introducing novel antipsychotic agents earlier in the course of
illness for restoration of individual quality of life merit further
investigation.
PMID- 10192405
TI - Management of acute mania.
AB - Bipolar disorder is a lifelong episodic condition characterized by mood swings
between mania and depression. In the United States alone, approximately 4 million
people are affected by this disorder. Pharmacologic treatment for acute manic
episodes or as maintenance therapy includes lithium, valproate, carbamazepine,
and typical antipsychotics. However, many patients fail to respond to these
treatments due to lack of efficacy or production of side effects leading to
patient noncompliance. Non-compliance with pharmacologic treatment is indeed a
major risk factor in bipolar disorder patients and needs to be managed with
ongoing education, psychotherapy, and a simplified but effective pharmacologic
treatment regimen. Recently introduced novel antipsychotics show much promise as
mood-stabilizing agents in bipolar patients, with minimal risk of treatment
emergent extrapyramidal symptoms and tardive dyskinesia. Nonetheless, further
research is warranted to help clarify the role of novel antipsychotics in the
treatment of bipolar disorder.
PMID- 10192406
TI - Mood-stabilizing drugs in depression.
AB - Mood-stabilizing drugs including lithium, anticonvulsants, and antipsychotics
have established effects in the management of bipolar disorder, especially in
mania. However, these drugs also have been shown to be effective in depressed
patients. For example, lithium is well established as an effective augmenting
strategy with tricyclic antidepressants in refractory depression. This article
will review a variety of effects of mood-stabilizing drugs in bipolar and
unipolar depressed patients, which will include acute treatment, prevention of
relapse and recurrence, and the management of refractory patients. The effects of
antipsychotics (especially atypicals) and new research directions also will be
reviewed.
PMID- 10192408
TI - Screening procedure for detection of dihydropyridine calcium channel blocker
metabolites in urine as part of a systematic toxicological analysis procedure for
acidic compounds by gas chromatography-mass spectrometry after extractive
methylation.
AB - A gas chromatographic-mass spectrometric (GC-MS) screening procedure was
developed for the detection of dihydropyridine calcium channel blocker ("calcium
antagonist") metabolites in urine as part of a systematic toxicological analysis
procedure for acidic drugs and poisons after extractive methylation. The part of
the phase-transfer catalyst remaining in the organic phase was removed by solid
phase extraction on a diol phase. The compounds were separated by capillary GC
and identified by computerized MS in the full scan mode. Using mass
chromatography with the ions m/z 139, 284, 297, 298, 310, 312, 313, 318, 324, and
332, the possible presence of calcium channel blocker metabolites could be
indicated. The identity of positive signals in such mass chromatograms was
confirmed by comparison of the peaks underlying full mass spectra with the
reference spectra recorded during this study. This method allowed the detection
of therapeutic concentrations of amlodipine, felodipine, isradipine, nifedipine,
nilvadipine, nimodipine, nisoldipine, and nitrendipine in human urine samples.
Because urine samples from patients treated with nicardipine were not available,
the detection of nicardipine in rat urine was studied. The overall recovery
ranged between 67 and 77% with a coefficient of variation of less than 10%, and
the limit of detection was at least 10 ng/mL (signal-to-noise ratio = 3) in the
full-scan mode.
PMID- 10192407
TI - Tardive dyskinesia in affective disorders.
AB - Soon after the introduction of antipsychotic drugs into clinical practice, these
agents were observed to be capable of producing not only acute extrapyramidal
("parkinsonian") side effects, but also later occurring abnormal involuntary
movements that came to be called tardive dyskinesia. Since antipsychotic drugs
are used in a variety of conditions that include psychotic features, studies have
attempted to determine whether specific diagnostic subgroups may experience
different degrees of vulnerability to drug-induced movement disorders. This issue
is important not only to inform clinical practice, but also to provide clues to
pathophysiology. A number of studies suggest that patients with affective
disorders are at greater risk for developing tardive dyskinesia (controlling, to
the extent possible, for other relevant variables such as age, sex, length of
treatment). Encouraging preliminary data with new antipsychotic drugs such as
olanzapine suggest that the risk of tardive dyskinesia associated with long-term
antipsychotic drug use may be substantially reduced. This would go a long way
toward improving the benefit-to-risk ratio of antipsychotic drug treatment,
particularly in patients with affective disorders.
PMID- 10192409
TI - A pilot study to determine the usefulness of the urinary excretion of methadone
and its primary metabolite (EDDP) as potential markers of compliance in methadone
detoxification programs.
AB - Fourteen subjects (selected on the basis of compliance with the methadone
maintenance program prescribed by the consultant psychiatrist in charge of their
treatment) undergoing opiate detoxification by methadone-replacement therapy were
studied to determine if a relationship exists between the dose of methadone
prescribed and the urinary excretion of methadone and/or its primary metabolite,
2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP). After the derivation of
this relationship, it was hoped that the urinary concentrations of methadone
and/or EDDP could be used as a noninvasive technique to monitor the methadone
compliance of 56 drug abusers. Despite statistically significant correlations
(p<0.001) between methadone dose and urine concentrations of methadone and EDDP,
the large variation in concentrations measured in the urine of drug abusers
negated the possibility of any clear-cut relationship being confirmed. However,
it may be possible to use excretion data to monitor individual compliance but
only through long-term monitoring of individual subjects to establish their own
intraindividual variation in excretion patterns.
PMID- 10192410
TI - Determination of alkylmethylphosphonic acids, the main metabolites of
organophosphorus nerve agents, in biofluids by gas chromatography-mass
spectrometry and liquid-liquid-solid-phase-transfer-catalyzed
pentafluorobenzylation.
AB - A simple gas chromatography-mass spectrometry (GC-MS) procedure has been
developed for the main metabolites of organophosphorus nerve agents,
alkylmethylphosphonic acids (AMPAs; alkyl = Et, i-Pr, and pinacolyl) in biofluids
via extractive pentafluorobenzylation. The derivatization was carried out under
liquid-liquid-solid-phase-transfer conditions using a polymer-bound tri-n
butylmethylphosphonium bromide as a catalyst. AMPAs in aqueous samples were
semiquantitatively extracted into a small-volume organic layer as their
pentafluorobenzyl derivatives at pH 4.5 (85 degrees C). Sample pretreatments for
urine, serum, and saliva were each examined to minimize matrix interference. The
detection limits of APMAs by electron-impact ionization GC-MS were around 50
ng/mL and 2.5-10 ng/mL in the full-scan and selected-ion monitoring modes,
respectively. In order to detect trace-level AMPAs, negative-ion chemical
ionization (NICI) was also employed to enhance sensitivity. The detection limits
of AMPAs in biofluids were typically 60 pg/mL by GC-NICI-MS.
PMID- 10192411
TI - Fluorimetric determination of aluminum traces in hemodialysis solutions using
Mordant Red 19.
AB - A sensitive and accurate method for the spectrofluorimetric determination of
trace levels of aluminum in hemodialysis solutions using Mordant Red 19 as the
complexation reagent has been developed. The optimal experimental conditions for
the concentration of fluorimetric reagent, pH, temperature, and the specific type
of matrix are reported. The emission of the fluorescent metal chelate was
measured at 555 nm, excitation at 478 nm. Linearity between emission intensity
and aluminum concentration was found in the 2-20 ppb range in standard aluminum
solutions. Limit of detection was 0.4 ppb. The aluminum amounts in some
commercial hemodialysis solutions were determined by means of the extrapolation
method. The proposed method proved to be suitable in terms of sensitivity and
accuracy for the determination of aluminum in dialysis fluids.
PMID- 10192412
TI - Amitriptyline and procainamide inhibition of cocaine and cocaethylene degradation
in human serum in vitro.
AB - Amitriptyline (AMI) and procainamide (PA) have been reported to inhibit the
activity of human plasma butyrylcholinesterase, an enzyme important in the
metabolic degradation of cocaine (COC) and its ethyl analogue cocaethylene (CE).
Because both AMI and PA may be used in the treatment of COC intoxication and
abuse, the effect of high pharmacological concentrations of these compounds on
the degradation of COC and CE in pooled human serum was studied. AMI (1.8
micromol/L) modestly inhibited the degradation of COC by 4.2% and of CE by 4.0%.
PA (42.5 micromol/L) profoundly inhibited degradation of COC by 42.7% and of CE
by 47.2%. In contrast, lithium carbonate (1 mmol/L, control) showed no inhibition
of degradation of either COC or CE. These results suggest that AMI and PA may
prolong the half-life of COC and CE in human serum.
PMID- 10192413
TI - Interference in the quantitation of methylated arsenic species in human urine.
AB - The aim of this paper is to report on the presence of chemical interferences in
the quantitation of methylated arsenic species in human urine when using a method
based on selective volatile arsine species generation, chromatographic
separation, and hydride generation atomic absorption spectrometry (HGAAS)
detection. An abnormal profile of methylated arsenic species characterized by the
absence of the peak corresponding to dimethylarsinic acid (DMA) was observed in
urine from some individuals exposed to arsenic via drinking water and living in
rural communities of northwestern Argentina. The absence of this peak persisted
even after the addition of known amounts of DMA to the samples. However, the DMA
peak appeared after urine digestion with hydrochloric acid (2M). Samples showing
interferences were provided by individuals who had mate consumption and coca-leaf
chewing habits. Because the relative proportions of methylated arsenic species
present in urine have been used to evaluate the efficiency of the methylation
process, interferences in the formation or detection of methylarsines may cause
underestimation of As exposure and also lead to erroneous conclusions about
relative biomethylation efficiencies. Therefore, we recommend that urine samples
should be digested with 2M HCl before performing speciation analysis using HGAA
techniques. Further studies on the impact of this type of interferences on other
arsenic speciation methods are also required.
PMID- 10192414
TI - Determination of tin, vanadium, iron, and molybdenum in various matrices by
atomic absorption spectrometry using a simultaneous liquid-liquid extraction
procedure.
AB - An atomic-absorption spectrometric method is described for the determination of
tin, vanadium, iron, and molybdenum in two certified reference materials, food
samples, and petroleum crude. After treatment with acids, these elements are
separated from matrix elements by simultaneous solvent extraction of 5,5'
methylenedisalicylohydroxamic acid complexes from HCl/NaClO4 solution into an
isobutyl methyl ketone/tributyl phosphate solution. The detection limits range
from 0.018 to 0.19 microg/mL (n = 3), and the relative standard deviations do not
exceed 2.0% at levels of 0.5, 0.6, 2.0, and 7.0 microg/mL of Fe, Mo, V, and Sn,
respectively. The method is selective and suffers only from interference by
Zr(IV), Ti(IV), Th(IV), W(VI), PO4(3-), and F-.
PMID- 10192415
TI - Determination of salbutamol and detection of other beta-agonists in human
postmortem whole blood and urine by GC-MS-SIM.
AB - This paper details a sensitive and quantitative method for the determination of
salbutamol and the detection of terbutaline, clenbuterol, fenoterol, and
isoprenaline in postmortem human whole blood and urine. It describes solid-phase
extraction using a XtrackT XRDAH515 column, formation of trimethylsilyl
derivatives, and analysis by gas chromatography-mass spectrometry-selective ion
monitoring.
PMID- 10192416
TI - Accuracy of five on-site immunoassay drugs-of-abuse testing devices.
AB - Many current "on-site" urine drug-testing products claim performance equivalent
to laboratory testing. Five commercially available products (PharmScreen, Roche
TestCup, Accusign DOA 2, Status DS, and American Bio Medica-Rapid Drug Screen)
were challenged with quality-control specimens of known drug metabolite
concentrations, 25% above and 25% below the SAMHSA cutoffs, and with known
positive and negative donor specimens previously analyzed by immunoassay and gas
chromatography-mass spectrometry. The results indicate discrepancies between
claims and performance for all products, particularly with amphetamines. The
implications for employer-based drug testing are discussed.
PMID- 10192417
TI - Oxaprozin interference with urinary benzodiazepine immunoassays and
noninterference with receptor assay.
PMID- 10192418
TI - Perphenazine distribution in a postmortem case.
AB - The case of a 34-year-old, mentally challenged, Caucasian female found dead in a
group home is presented. Empty containers of perphenazine and valproic acid were
found next to her bed. The perphenazine had been prescribed to another patient.
No anatomic cause of death was determined at autopsy. Comprehensive testing of
the heart blood for ethanol and drugs identified perphenazine at a concentration
of 4.4 mg/L and valproic acid at a concentration of 950 mg/L. The distribution of
perphenazine in other specimens was consistent with previously reported
phenothiazine cases. The medical examiner ruled that the cause of death in this
case was multiple drug intoxication and the manner of death was suicide.
PMID- 10192419
TI - Self-intoxication with morphine obtained from an infusion pump.
AB - A 36-year-old Caucasian male was found unresponsive by his wife. He had white
foam around his mouth and was pronounced dead shortly thereafter. He had a
history of back pain and was treated with intrathecal morphine because of his
previous addiction to oral opiate medications. Because of crimping of the pump
catheter, it was replaced 4 days before his death. Toxicological findings
included urine screen positive for amitriptyline, nortriptyline, opiates,
hydrocodone metabolites, ibuprofen, acetaminophen, caffeine, nicotine, and
metabolite. Drug concentrations were as follows: blood, 0.260 mg/L amitriptyline,
0.160 mg/L nortriptyline, 0.460 mg/L unconjugated morphine, and 0.624 mg/L total
morphine; vitreous humor, 0.034 mg/L unconjugated morphine and 0.080 mg/L total
morphine; and cerebrospinal fluid, 0.099 mg/L unconjugated morphine and 0.095
mg/L total morphine. Shortly after death, the volume of the residual pump
reservoir was only 8 mL instead of the expected 17 mL. Testing by the FDA showed
that the pump was functional. The residual content of the pump accounted for only
230 mg instead of the expected 488 mg. The high blood-morphine concentrations did
not correlate with the intrathecal infusion dose. The symptoms were consistent
with opiate overdose, possibly by injection of morphine withdrawn from the pump
reservoir. The cause of death was determined to be fatal morphine self
intoxication, and the manner of death was accidental. This case is intended to
alert regulatory agencies, pain management health professionals, pathologists,
and toxicologists to the abuse potential of one of the newer analgesic-delivery
systems.
PMID- 10192420
TI - A safer method for the measurement of plasma thiocyanate.
PMID- 10192421
TI - Heinz body haemolytic anaemia in Wilson's disease.
PMID- 10192422
TI - The impact of the new fish technologies on the cytogenetics of haematological
malignancies.
PMID- 10192423
TI - Molecular evolution of acute myeloid leukaemia in relapse: unstable N-ras and
FLT3 genes compared with p53 gene.
AB - Relapse is a major cause of treatment failure in acute myeloid leukaemia (AML),
and is usually accompanied by resistance to chemotherapy. To study whether
relapse is accompanied by genetic alterations, we compared N-ras, p53 and FLT3
gene mutations in paired samples obtained at initial diagnosis and first relapse.
28 patients with relapsed AML were studied, and their duration of complete
remission ranged from 133 to 989 d (mean 318 d). Karyotype changes were observed
at relapse in 11 patients. Point mutations of the N-ras gene were positive at
both stages (+/+) in three patients, positive at initial diagnosis and negative
at relapse (+/-) in three patients, and negative at initial diagnosis and
positive at relapse (-/+) in two patients. Internal tandem duplications of the
FLT3 gene (FLT3/ITD) were +/+ in five patients, +/- in one patient, and -/+ in
six patients. The p53 gene mutations were +/+ in two patients, +/- in one
patient, and -/- in 25 patients. FLT3/ITD and mutant p53 at relapse were
associated with short survival after relapse. These results indicate that relapse
is frequently accompanied by molecular alterations that include the loss and/or
acquisition of mutations. Thus relapse can be understood as clonal shift or
collateral succession rather than clonal progression.
PMID- 10192424
TI - Molecular characterization of deletion at 11q22.1-23.3 in mantle cell lymphoma.
AB - Chromosomal deletions at 11q21-23 have recently been reported to be common
aberrations in mantle cell lymphoma (MCL). To characterize the structure of the
deletion, we studied 41 cases of MCL by fluorescence in situ hybridization using
a YAC contig, which spans the region at 11q22.1-23.3. 17 MCLs were studied using
a set of 20 yeast artificial chromosomes (YACs) in a contig, and nine of these
cases showed deletion of 11q22-23. The deletion spanned several megabases in all
but one case, where only YAC 755b11 at 11q23.1, covering approximately a 1.6 Mb
of DNA, was deleted. Analysis of additional 24 MCLs with YAC 755b11 revealed the
deletion in 49% of all cases (20/41). The deleted region at 11q22.1-23.3 was
discontinuous in five lymphomas and in the majority of the cases the distal
breakpoint occurred between YACs 785e12 and 911f2 at 11q23.3. We conclude that
the deletion of 11q22-23 and particularly the deletion of YAC 755b11 are very
common in MCL and may be important in the genesis or progression of the disease.
PMID- 10192425
TI - B-cell lymphoma associated with haemophagocytic syndrome: a clinical,
immunological and cytogenetic study.
AB - B-cell lymphoma associated with haemophagocytic syndrome (HPS) is extremely rare
in Western countries but has recently been increasingly reported in Asian
countries. We describe seven patients with B-cell lymphoma associated with HPS,
six males and one female, age range 41-82 years (median 63 years). All patients
had fever and splenomegaly, and six of the seven patients had hepatomegaly with
no associated lymphadenopathy. The bone marrow showed haemophagocytosis and an
infiltration of lymphoma cells. All patients showed increased levels of lactate
dehydrogenase, C-reactive protein, ferritin and soluble interleukin-2 receptor.
Lymphoma cells were positive for CD19. CD20 and surface immunoglobulin in all
patients examined, and positive for CD5 in four of seven patients. Cytogenetic
analyses of bone marrow cells showed a complex structural abnormality including
chromosome 14q32 in two patients, 19q13 in three patients and deletion of the
terminal part of 8p21 in six patients. The prognosis was poor; only two of the
seven patients have survived in complete remission with a median survival of 11
months. These data suggested that B-cell lymphoma associated with HPS might
constitute a distinct biological and clinical disease entity. Abnormality of
chromosome 19q13 and loss of 8p21 might be involved in the pathogenesis of this
disease.
PMID- 10192426
TI - Leukaemic presentation of small cell variant anaplastic large cell lymphoma:
report of four cases.
AB - We report four cases of a rare subtype of CD30-positive anaplastic large cell
lymphoma (ALCL) with a predominant small cell component (small cell variant of
ALCL) presenting with a leukaemic feature. Lymph node biopsy showed malignant
cells of varying size with a predominant population of small to medium-sized
malignant cells associated with large anaplastic cells strongly positive for CD30
and epithelial membrane antigen (EMA). Both large and small cells were reactive
with antibody ALK1, which recognizes the chimaeric NPM-ALK protein associated
with the t(2;5)(p23;q35). All patients presented with hyperleucocytosis with
atypical small lymphocytes. Bone marrow involvement was detected on both aspirate
and bone marrow trephine where scattered malignant cells were only demonstrated
by immunostaining for CD30 and ALK protein. Atypical cells in peripheral blood,
lymph node and skin biopsies showed a T or null cell phenotype. Cytogenetic
analysis of blood, bone marrow and/or lymph node revealed the t(2:5)(p23;q35)
characteristic of ALCL. The patients responded to chemotherapy but showed early
relapse without abnormal cells in peripheral blood. This report shows that the
small cell variant of ALCL may have a leukaemic presentation with peripheral
blood involvement by atypical lymphocytes and provides evidence that, in the
small cell variant of ALCL, the small cell component is a part of the malignant
clone.
PMID- 10192427
TI - Chronic lymphocytic leukaemia with symptomatic diffuse central nervous system
infiltration responding to therapy with systemic fludarabine.
AB - B-cell chronic lymphocytic leukaemia is an indolent disease characterized by the
insidious accumulation of small mature-appearing lymphocytes in the peripheral
blood, bone marrow and lymphoid tissues. Direct symptomatic invasion of the
central nervous system is exceedingly rare and, to our knowledge, only three
cases histologically confirmed as true chronic lymphocytic leukaemia have been
reported in the literature. We describe the first case of early Rai stage B-cell
chronic lymphocytic leukaemia presenting with symptomatic infiltration of the
brain and spinal cord which could be demonstrated radiographically by magnetic
resonance imaging. The diagnosis was confirmed by examination of peripheral
blood, cerebrospinal fluid, brain and bone marrow biopsies, both morphologically
and immunophenotypically by means of flow cytometric analysis. The patient
demonstrated a complete response to therapy with standard-dose systemic
fludarabine and remains in complete remission 6 months after completion of
therapy.
PMID- 10192428
TI - Detection of abnormalities in B-cell differentiation pattern is a useful tool to
predict relapse in precursor-B-ALL.
AB - Immunophenotypic investigation of minimal residual disease (MRD) has
traditionally been based on the investigation of phenotypic aberrants at
diagnosis to be used later as a target for MRD detection. This approach has
several shortcomings (it is only applicable to patients with aberrant phenotypes,
requires a diagnostic sample, and is patient-specific) and therefore a search for
simpler alternatives is warranted. The present study is based on the hypothesis
that in precursor-B-ALL patients the persistence of residual leukaemic cells may
induce abnormalities in the precursor-B-cell compartment in bone marrow (BM) and
these could be used as a criteria to predict relapse. These abnormalities may
include: (1) the presence of an increase in the frequencies of immature B cells
(CD34+/CD19+ or CD20-/CD19+) or (2) the existence of an altered B-cell
differentiation pathway due to a blockade or to the presence of B cells outside
the normal pathway. A total of 180 BM samples from 45 consecutive precursor-B-ALL
patients who achieved morphological complete remission (CR) were analysed by
multiparametric flow cytometry. Our results show that a significant increase in
immature B-cell subsets or an altered B-cell differentiation predicts a high
relapse rate (P<0.01) and a shorter disease-free survival (P<0.01). Moreover,
abnormalities in either of these two criteria detected at specific time points
during follow-up (end of induction, maintenance, or after treatment) were
associated with a significantly shorter disease-free survival (P<0.01). In
summary, the investigation of abnormalities in B-cell differentiation is a
relatively simple and cheap approach for predicting relapse in precursor-B-ALL
patients.
PMID- 10192429
TI - Increased adhesion of the promyelocytic leukaemia cell line, NB4, to fibronectin
and thrombospondin upon all-trans-retinoic acid treatment.
AB - We have evaluated the effects of all-trans-retinoic acid (RA) on the adhesion of
the human promyelocytic cell line NB4 to various components of the extracellular
matrix. NB4 cells, radiolabelled with (111)Indium, showed a 2-3-fold increase (P
< 0.001) in adhesion to fibronectin and thrombospondin upon RA (3 x 10(-7)
microM) treatment, whereas adhesion to collagen I, laminin and vitronectin was
not modified. The increase in cell adhesion, observed as early as day 1, preceded
cell differentiation and was concomitant with tyrosine phosphorylation events.
Using flow cytometry, we analysed the expression of major receptors for
fibronectin (alpha4beta1 and alpha5beta1) and for thrombospondin (alpha(v)beta3,
alpha(IIb)beta3, CD36 and CD47) on NB4 cells before and after RA treatment.
Except for alpha(IIb)beta3, which was induced on RA-treated cells, we found no
significant increase in the expression of the other receptors, and a decrease in
the expression of CD36, upon RA treatment. Preincubation of RA-treated cells with
blocking antibodies demonstrated a role for alpha4beta1 and alpha5beta1 in cell
adhesion to fibronectin and alpha5beta1, alpha(IIb)beta3, CD36 and CD47 in cell
adhesion to thrombospondin. Experiments with the synthetic peptides GRGDS (0.2
mM) and CSVTCG (0.2 mM) confirmed the participation of integrins, and integrins
and CD36, in adhesion of RA-treated cells to fibronectin and thrombospondin,
respectively. Further inhibition by heparin (10 microg/ml) and/or recombinant
heparin-binding domain of thrombospondin (TSP18) indicated the additional
participation of heparin-like receptors in cell adhesion to thrombospondin. Our
results indicate that increase in NB4 cell adhesion to fibronectin and
thrombospondin upon RA treatment is likely to occur through a modulation of the
functional state of several receptors for these proteins.
PMID- 10192430
TI - Potential role of insulin-like growth factor binding protein-4 in the uncoupling
of bone turnover in multiple myeloma.
AB - Decreased bone formation plays an important role in the development of lytic
lesions during the late stage of multiple myeloma (MM). Release of insulin-like
growth factor binding protein-4 (IGFBP4) by tumour cells adjacent to bone may
inhibit IGF-I-stimulated osteoblast growth and contribute to decreased bone
formation. The present study demonstrates that the human MM cell line, ARH-77,
expresses IGFBP4 and, to a lesser extent, IGFBP6 mRNA and protein. IGFBP4
expression in myeloma cells may be modulated by cytokines released by stromal
cells and T cells in the microenvironment. We tested the effect of recombinant
interferon-gamma (INF) on IGFBP4 expression in ARH-77. INF increased IGFBP4 mRNA
and protein levels at 12 h, with a decline to baseline by 24 h. In contrast,
IGFBP4 was not regulated in response to IL-6, TNF-alpha, PDGF BB, bFGF, TGF-beta
or the cAMP agonist, forskolin. In other systems. IGFBP4 may also be regulated
post-transcriptionally by a protease that is activated by IGF-I or -II.
Conditioned medium from ARH-77 cultures incubated with IGF-I or -II for up to 24
h failed to demonstrate proteolytic activity. Proteolysis was also not observed
when conditioned medium containing exogenous rhIGFBP4 was incubated with IGF-I or
-II under cell-free conditions. To determine if human myeloma tumours also
express IGFBP4, total RNA was isolated from four tumour biopsies. All samples
expressed detectable levels of IGFBP4 mRNA. These findings indicate that
interferon-gamma may indirectly modulate bone formation via the the release of
tumour-derived IGFBP4. suggesting that the immune system may influence bone
turnover in MM. Failure of myeloma cells to release protease activity may promote
IGFBP4 accumulation in the microenvironment during tumour growth.
PMID- 10192431
TI - Prognostic value of vertebral lesions detected by magnetic resonance imaging in
patients with stage I multiple myeloma.
AB - We assessed the role of spinal magnetic resonance imaging (MRI) and bone
densitometry as prognostic factors in patients with asymptomatic stage I multiple
myeloma (MM) and negative skeletal survey. 55 consecutive patients underwent
spinal MRI and 41 of them underwent bone densitometry by dual-energy X-ray
absorptiometry (DEXA). Spinal MRI studies showed evidence of bone marrow
involvement in 17/55 patients (31%). A diffuse pattern was present in three
patients and a focal pattern in 14 patients, nine of them with only one nodular
lesion. During a median follow-up of 25 months, 10 patients had disease
progression, 8/17 patients with abnormal MRI and 2/38 patients with normal MRI.
Median time to disease progression was not reached in both groups but was
significantly different for patients with normal and those with abnormal patterns
on MRI (P < 0.0001). Lumbar BMD was only slightly decreased compared with normal
people (median lumbar Z score -0.43) and was not of prognostic value. Using a
multivariate analysis the only two independent significant prognostic parameters
were abnormal MRI (P<0.001, HR 30.4, 95% CI 4.3-213) and bone marrow
plasmacytosis >20% (P=0.004, HR 16.4, 95% Cl 2.6-104). Thus, spinal MRI but not
bone densitometry, appeared to be justified in patients with stage I asymptomatic
MM and negative skeletal survey.
PMID- 10192432
TI - The Italian Consensus Conference on Diagnostic Criteria for Myelofibrosis with
Myeloid Metaplasia.
AB - The purpose of this work was to develop a definition of myelofibrosis with
myeloid metaplasia (MMM) using diagnostic criteria that would remain valid within
the set of patients with chronic myeloproliferative disorders or myelodysplastic
syndromes. A list of 12 names for the disease and 37 diagnostic criteria were
proposed to a Consensus Panel of 12 Italian experts who ranked them in order so
as to identify a core set of criteria. The Panel was then asked to score the
diagnosis of 46 patient profiles as appropriate or not appropriate for MMM. Using
the experts' consensus as the gold standard, the performance of 90 possible
definitions of the disease obtained through the core set was evaluated.
'Myelofibrosis with myeloid metaplasia' ranked as the preferred name of the
disease. Necessary criteria consisted of 'diffuse bone marrow fibrosis' and
'absence of Philadelphia chromosome or BCR-ABL rearrangement in peripheral blood
cells'. The six optional criteria in the core set consisted of: splenomegaly of
any grade; anisopoikilocytosis with tear-drop erythrocytes; the presence of
circulating immature myeloid cells; the presence of circulating erythroblasts:
the presence of clusters of megakaryoblasts and anomalous megakaryocytes in bone
marrow sections; myeloid metaplasia. The definition of the disease with the
highest final score was as follows: necessary criteria plus any other two
criteria when splenomegaly is present or any four when splenomegaly is absent.
The use of this definition will help to standardize the conduct and reporting of
clinical studies and should help practitioners in clinical practice.
PMID- 10192433
TI - Alterations of the retinoic acid receptor alpha (RAR alpha) gene in myeloid and
lymphoid malignancies.
AB - The retinoic acid receptor alpha (RAR alpha) protein plays a central role in
myeloid differentiation, and chromosomal translocations disrupting the RAR alpha
gene are implicated in the development of acute myeloid leukaemia (AML). To
identify haemopoietic malignant disorders which may also be linked to RAR alpha
abnormalities, Southern blot analysis was performed in DNA from 153 patients with
haematological malignancies other than AML FAB type M3 using RAR alpha cDNA
probes. Alterations of RAR alpha were detected in 1/42 myelodysplastic syndromes
(MDS), 2/24 AML, 3/47 B-chronic lymphocytic leukaemias (B-CLL), 0/40 lymphomas
and 0/60 normal individuals. These data strongly suggest that alterations of RAR
alpha might predispose for myeloid and lymphoid disorders.
PMID- 10192434
TI - The sequential analysis of trisomy 12 in B-cell chronic lymphocytic leukaemia.
AB - In this longitudinal study we evaluated the clinical significance of screening
for trisomy 12 by fluorescence in situ hybridization (FISH) and correlated these
findings with survival, disease progression and need for treatment. Interphase
FISH was performed on 85 patients in 1993/94 and repeated on 41 patients in
1996/97. Over the 4-year period there was no significant change in the percentage
of trisomic cells, even in patients with disease progression. Overall survival
and requirement for treatment were similar for patients with and without FISH
defined trisomy 12.
PMID- 10192435
TI - Pulmonary Aspergillus colonization in humans and its impact on management of
critically ill patients.
AB - Samples of lung tissues were obtained and analysed for Aspergillus carriage in 56
patients undergoing thoracic surgical intervention and 18 people who had an
unexpected death. Out of 74 samples, 46 (63%) had evidence of pulmonary fungal
colonization. The surgery population had a rate of 62% of fungal growth.
Aspergillus was present in 39%. The autopsy population had a rate of 61% of
fungal colonization. Aspergillus was present in 41%. In these cases eradication
of fungal spores residing in the lung prior to aggressive chemotherapy and
prevention of further spore uptake during hospitalization is indispensable in
preventing pulmonary aspergillosis.
PMID- 10192436
TI - Multiple myeloma related cells in patients undergoing autologous peripheral blood
stem cell transplantation.
AB - A high incidence of oligoclonal serum M-components is observed in multiple
myeloma (MM) patients treated with autologous stem cell transplantation (ASCT).
To determine whether these M-components are produced by myeloma clonally related
cells or caused by an aberrant B-cell regeneration we analysed by semi-nested ASO
RT-PCR and DNA sequencing the immunoglobulin (Ig) variable genes (VH) obtained
from bone marrow samples obtained before and after transplantation and peripheral
blood stem cell (PBSC) samples from seven patients. Myeloma clonally related
cells are identifiable by the expression of variant Ig heavy chain isotypes and
were detected in two patients at presentation. No myeloma clonally related cells
were found in post-transplantation samples (n = 7) in spite of the appearance of
new serum M-components. However, in two cases we amplified sequences from post
transplantation bone marrow cells that were able to bind to the B-cell clone
specific CDR3 oligonucleotides but showed no further similarity regarding the VDJ
rearrangement. These data indicate that serum oligoclonality post-transplantation
is not caused by myeloma clonally related B cells but rather by the regenerating
B-cell compartment.
PMID- 10192437
TI - Induction-consolidation with an idarubicin-containing regimen, unpurged marrow
autograft, and post-graft chemotherapy in adult acute lymphoblastic leukaemia.
AB - Between 1991 and 1993 we conducted a collaborative trial in adult acute
lymphoblastic leukaemia, introducing an idarubicin (IDA)-containing regimen for
induction and early consolidation, and increasing consolidation intensity with an
autologous bone marrow transplantation phase (ABMT, patients aged <51 years)
followed by further chemotherapy for 12 weeks and low-dose maintenance for 6
months (ABMT patients) or 18 months. 96 patients were evaluable for antileukaemic
response after induction with vincristine-prednisone-L-asparaginase plus
cumulative IDA 36 or 20 mg/m2 (IVAP-1 and IVAP-2), and for disease-free survival
(DFS) after a minimum follow-up >3.5 years with an off-therapy interval >1.5
years. The response rate was 44% (7/16) with IVAP-1 and 90% (72/80) with IVAP-2
(P=0.0001), due to regimen-related toxicities. Post-remission therapy was
administered as planned to most cases but protocol violation was registered in
some patients eligible to ABMT and post-graft chemotherapy. The 5-year disease
free survival (DFS) rate was 31%. Multivariate analysis indicated that DFS was
improved in patients receiving a transplant (11 allogeneic, DFS 70%; 32 ABMT,
36%; 37 neither, 17%; P < 0.001) and was negatively affected by high-risk
features such as blast cell count >25x10(9)/l, T-cell or mature B-cell
immunophenotype, and t(9;22)/t(4;11) (all P values <0.05). The 5-year DFS rate
was 54% for 26 patients with no high-risk factor, 26% for 35 patients with any
one, and 6% for 18 patients with any two (P<0.005). IVAP-2 brought about a high
complete response rate and post-remission treatment including ABMT was feasible
and modestly toxic. In spite of the short post-graft chemotherapy phase, the long
term DFS rate was good in cases with no high-risk feature. However, because
autografting may be redundant in the standard-risk category, its role requires
further investigation for high-risk cases.
PMID- 10192438
TI - A prospective study of risk-adapted therapy for large cell non-Hodgkin's lymphoma
with VACOP-B followed by high-dose CBV and autologous progenitor cell
transplantation for high-risk patients in remission.
AB - Several centres reported a favourable outcome after high-dose chemotherapy with
autologous progenitor cell transplantation in selected patients with high-risk
large cell non-Hodgkin's lymphoma in first remission. Based on these
observations, we wanted to prospectively determine the outcome of a risk-adapted
therapy for patients with large cell lymphoma. Patients aged 60 years or less
received 12 weeks of VACOP-B chemotherapy. For high-risk patients in remission
this was immediately followed by high-dose chemotherapy with cyclophosphamide,
carmustine and etoposide and autologous progenitor cell transplantation. High
risk criteria were defined before the establishment of the International Index
and included large cell lymphoma stage III or IV or mediastinal large lymphoma
with sclerosis stage II or higher, and the presence of bulky tumours and/or an
elevated LDH. 89 patients fulfilled the clinical selection criteria and were
entered onto this multicentre study. 82 patients were evaluable after
confirmation of large cell histology by pathology review. Of these, 51 were
considered to be in the low-risk group and 31 in the high-risk group. The 3-year
event-free survival for all patients was 68%. The 3-year event-free survival was
76% for the low-risk and 55% for the high-risk group (P = 0.061). Only 22/31 high
risk patients were able to receive the high-dose chemotherapy in first remission
as intended. In conclusion, although our study demonstrated that a risk-adapted
therapy for large cell lymphoma could be safely administered, the potential
impact on outcome of the strategy chosen here is likely to be small.
PMID- 10192439
TI - A prospective molecular study of chimaerism in patients with haematological
malignancies receiving unrelated cord blood or bone marrow transplants: detection
of mixed chimaerism predicts graft failure with or without early autologous
reconstitution in cord blood recipients.
AB - We prospectively studied the chimaerism status in the bone marrow (BM) and
peripheral blood (PB) of 23 patients receiving umbilical cord (UCB, 14 cases) or
BM (nine cases) transplants from unrelated donors by PCR amplification of four
individual-specific VNTR genetic loci. Haematological engraftment, with
persistent full donor pattern. was observed in 10/14 (72%) patients receiving UCB
and in 9/9 (100%) patients transplanted with marrow from an unrelated donor
(MUD). In contrast, the remaining four patients converted to an autologous
pattern. Three out of these four patients had an early autologous haematological
reconstitution reaching a neutrophil level >0.5 x 10(9)/l at days 27, 33 and 37
after transplant, respectively. In all three of these patients, chimaerism
analysis demonstrated an early appearance of donor cells (i.e. within 35 d after
UCB transplant) showing a transient full donor (one case) or mixed chimaerism
condition (two cases). Despite the early autologous haemopoietic reconstitution,
one of the three patients died of GVHD at day 60, which was explained by the
demonstration of low levels of donor lymphoid cells. In the MUD group all nine
patients converted to a persistent full donor pattern with haematological
reconstitution, accompanied in two of them by transient mixed chimaerism lasting
to days 60 and 270 after transplant. Our data show that monitoring of chimaerism
may predict graft failure with or without early autologous haemopoietic
reconstitution in patients receiving unrelated UCB transplants. Furthermore,
chimaerism analysis may identify, in patients with autologous reconstitution,
those at risk of severe GVHD in whom immunosuppressive therapy should not be
discontinued.
PMID- 10192440
TI - Prolonged release and c-kit expression of haemopoietic precursor cells mobilized
by stem cell factor and granulocyte colony stimulating factor.
AB - Mobilization of haemopoietic precursor cells into the circulation by the
combination of cytokines, stem cell factor (SCF) and G-CSF in previously
untreated patients with carcinoma of the breast resulted in increased yield of
collected peripheral blood precursor cells (PBPC). This mobilization of PBPC by
SCF with G-CSF lasted several days after ceasing the cytokines in comparison to
the rapid fall of PBPC after ceasing G-CSF. Possible mechanisms for this
increased and prolonged mobilization were investigated. Immunological phenotyping
with CD38, Thy-1 and MDR-1 of the CD34-positive mobilized PBPC detected no
difference in maturity compared to PBPC mobilized by G-CSF alone. However, the
down-regulation of c-kit, which is associated with the mechanism of mobilization,
was much greater in the PBPC mobilized by SCF and G-CSF. The potential clinical
implication of increased and prolonged mobilization is increased yield, allowing
transplantation of heavily pre-treated patients, transplantation with PBPC from a
single apheresis, or PBSC support for multiple courses of high-dose therapy from
one mobilization procedure.
PMID- 10192441
TI - Effect of insulin-like growth factor 1 on PHA-stimulated cord blood mononuclear
cell telomerase activity.
AB - Telomerase may contribute to the capacity for cell replication by compensating
for the loss of telomere length. Exploring the use of biological modifiers in
increasing cellular replicative potential through telomerase activity may be
useful for in vitro expansion of haemopoietic stem cells for transplantation or
lymphoid cells for adoptive immunotherapy. In this study we showed for the first
time that insulin-like growth factor 1 (IGF-1) modulated telomerase activity in
human cord blood mononuclear cells (MNC) and some of the known functional
determinants of telomerase activity. We found that cord blood MNC expressed
constitutively a low level of telomerase activity and human telomerase reverse
transcriptase (hTRT) mRNA, and a high level of human telomerase RNA component
(hTR) and telomerase-associated protein-1 (TP1) mRNA. Interestingly, IGF-I alone
did not increase the telomerase activity of cord blood MNC but could enhance the
PHA-induced increase in telomerase activity. These alterations in telomerase
activity were not completely in phase with those of proliferation response. On
the other hand, IGF-I did not alter hTRT mRNA expression but enhanced the PHA
induced increase in hTRT whereas TP1 mRNA expression was stimulated by either IGF
I or PHA but showed no additive increase when stimulated by both IGF-1 and PHA.
Neither IGF-1 nor PHA altered hTR expression. Finally, the temporal dynamics of
hTRT mRNA expression and telomerase activity in cord blood MNC over 5 d in
culture were not totally concordant. suggesting that key factors other than hTRT
were involved in regulating telomerase activity in cord blood MNC. The modulatory
effect of IGF-1 on telomerase activity supports its potential role in increasing
replicative potential of cord blood lymphoid cells or haemopoietic stem cells.
PMID- 10192442
TI - Levels of soluble FasL and FasL gene expression during the development of graft
versus-host disease in DLT-treated patients.
AB - Three patients with different clinical symptoms of graft-versus-host disease
(GVHD) who had received donor lymphocyte transfusion (DLT) for the treatment of
relapsed leukaemia after an allogeneic bone marrow transplantation (BMT) from HLA
matched sibling donors were analysed for the presence of soluble FasL (sFasL) in
the sera and for the expression of the Fas ligand (FasL) gene in the peripheral
blood mononuclear cells (PBMNC). Two patients who demonstrated liver damage with
increased levels of serum bilirubin showed significantly increased levels of
serum sFasL. The increase in the sFasL level was observed prior to the increase
in the bilirubin during the clinical courses of both patients. The high dose of
methyl predonisolone administered to one of these patients greatly reduced the
levels of sFasL in the serum. The bilirubin levels were also reduced thereafter.
The third patient (without liver damage) did not show any increase in the serum
sFasL level. The expression of the FasL gene in the PBMNC of these three patients
was examined. All three patients showed increased levels of the FasL gene
expression during their clinical courses. However, only one patient showed a
parallel alteration of FasL gene expression with sFasL in the serum. These cases
provide evidence that the Fas/FasL system is closely associated with human GVHD,
especially in the development of liver GVHD.
PMID- 10192443
TI - Bone marrow CD34 cells generate fewer T cells in vitro with increasing age and
following chemotherapy.
AB - To assess the influence of high-dose chemotherapy and age on the intrinsic
capacity of stem cells to generate T cells, CD34+ cells derived from bone marrow
used in clinical transplantation were evaluated in an in vitro T-cell assay using
a mouse thymic microenvironment. CD34+ cells were sorted from healthy donor and
autologous back-up bone marrow after density gradient centrifugation and
depletion for CD1, 3, 4, 7, 8, 19 and glycophorin A using magnetic beads. CD34+
cells were then introduced in day 14-15 fetal SCII) mouse thymus lobes by
incubation in hanging drops for 48 h. After transfer to gelfoam rafts they were
cultured for variable time periods. The lobes were then homogenized in a tissue
grinder for flow cytometric analysis gating on human cells. These were evaluated
for CD4, CD8, CD3 and HLA-DR surface expression. 51 samples were analysed and
three patterns of T-cell precursor development could be observed. In pattern A no
human cells could be recovered, in pattern B maturation stopped at the CD4+ CD8-
CD3- pre-T-cell stage, and in pattern C maturation to double-positive CD4+ CD8+
thymocytes was reached. In 25 healthy donors under age 40 three showed pattern A,
12 pattern B and 10 pattern C, whereas in 16 healthy donors over the age 40 there
were respectively four with A, seven with B and only five with C (P=0.01). In 10
patients who had previously received chemotherapy, none developed pattern C, five
pattern B and five pattern A, in contrast to 15/41 pattern C, 19/41 pattern B and
7/41 pattern A in healthy donors. These data suggest an intrinsic loss of T-cell
generation capacity from adult bone marrow stem cells in comparison to reports on
stem cells of fetal origin. This loss correlated weakly with age, irrespective of
thymic involution, and may be further reduced by prior chemotherapy.
PMID- 10192444
TI - Identification of human T-lymphoid progenitor cells in CD34+ CD38low and CD34+
CD38+ subsets of human cord blood and bone marrow cells using NOD-SCID fetal
thymus organ cultures.
AB - In contrast to myeloid and B-lymphoid differentiation, which take place in the
marrow environment, development of T cells requires the presence of thymic
stromal cells. We demonstrate in this study that human CD34+, CD34+ CD38+ and
CD34+ CD38(low) cells from both cord blood and adult bone marrow reproducibly
develop into CD4+ CD8+ T cells when introduced into NOD-SCID embryonic thymuses
and further cultured in organotypic cultures. Such human/mouse FTOC fetal thymic
organ culture) thus represents a reproducible and sensitive system to assess the
T-cell potential of human primitive progenitor cells. The frequency of T-cell
progenitors among cord-blood-derived CD34+ cells was estimated to be 1/500.
Furthermore, the differentiation steps classically observed in human thymus were
reproduced in NOD-SCID FTOC initiated with cord blood and human marrow CD34+
cells: immature human CD41(low) CD8- sCD3- TCR alphabeta- CD5+ CD1a+ T cells were
mixed with CD4+ CD8+ cells and more mature CD4+ CD8- TCR alphabeta+ cells.
However, in FTOC initiated with bone marrow T progenitors, <10% double-positive
cells were observed, whereas this proportion increased to 50% when cord blood
CD34+ cells were used, and most CD4+ cells were immature T cells. These
differences may be explained by a lower frequency of T-cell progenitors in adult
samples, but may also suggest differences in the thymic signals required by bone
marrow versus cord blood T progenitors. Finally, since cytokine-stimulated CD34+
CD38(low) cells retained their ability to generate T cells, these FTOC assays
will be of value to monitor, when combined with other biological assays, the
influence of different expansion protocols on the potential of human stem cells.
PMID- 10192445
TI - Selective modulation of the cyclin B/CDK1 and cyclin D/CDK4 complexes during in
vitro human megakaryocyte development.
AB - Mammalian megakaryocyte development is characterized by a progressive
accumulation of cells exhibiting a polylobated nucleus with a polyploid DNA
content. In this study human megakaryocytes were obtained from CD34+ haemopoietic
progenitors by in vitro liquid culture in the presence of 100 ng/ml of
recombinant thrombopoietin (TPO). Ultrastructural examination of polyploid
megakaryocytes showed the presence of a large number of centrioles, the breakdown
of the nuclear envelope, and the progressive chromatin condensation, all aspects
characteristic of mitosis. At both indirect immunofluorescence and Western blot
analyses, cyclin B and its related cyclin-dependent kinase (CDK)1, which forms
the mitosis promoting factor (MPF), showed an increased expression in maturating
megakaryoblasts and megakaryocytes (day 8 of culture) with respect to freshly
isolated CD34+ progenitors. This expression tended to decline in fully developed
megakaryocytes (day 15 of culture). The amount of cyclin D and of the related
CDK4, governing the G1 phase of the cell cycle, increased during megakaryocyte
development, maintaining high levels of expression also in mature megakaryocytes.
These results indicate that megakaryocyte polyploidization depends on a true,
although incomplete, mitotic process, and that cyclin D/CDK4 probably plays a
crucial role throughout megakaryocytopoiesis.
PMID- 10192447
TI - An ELISA specific for murine erythropoietin.
AB - Murine recombinant erythropoietin (EPO) was purified from an EPO-producing cell
line and used for the production of polyclonal monospecific anti-murine EPO
antibodies in rabbits. The anti-mouse EPO antibodies were purified by two
affinity chromatography procedures. In order to obtain the most sensitive ELISA,
different antibody combinations were tested in the ELISA sandwich assay. The best
combination was achieved with an anti-human EPO antibody as coating and the
biotinylated anti-murine EPO antibody as detecting antibody. With this sandwich
ELISA a sensitive standard curve in the range of 0.6-30 mU/ml could be
established. The assay provides a sensitive and reliable measure of murine EPO in
serum and cell culture supernatants ranging from normal to highly elevated EPO
levels.
PMID- 10192446
TI - Erythroid gene expression is differentially regulated by erythropoietin, haemin
and delta-aminolaevulinic acid in UT-7 cells.
AB - Erythropoietin (Epo) is essential for the later stages of erythropoiesis, acting
to promote cell survival and proliferation, but its role in differentiation
remains to be defined. The UT-7 cell line exhibits both erythroid and
megakaryocytic characteristics and can be induced to differentiate along the
erythroid pathway by Epo or the megakaryocytic pathway by phorbol myristic
acetate. We have compared the effects of Epo and the chemical inducers, delta
aminolaevulinic acid (delta-ALA) and haemin on the differentiation capacity of UT
7 cells. Epo alone promoted relatively early events in erythroid maturation,
without significant changes in haemoglobin production or morphology. GATA-2 and c
myb were down-regulated by Epo, and GATA-2 was further down-modulated by the
inducers. Conversely, SCL expression was up-regulated by Epo and further
increased by haemin and delta-ALA. Epo caused an increase in the proportion of
cells expressing cell surface glycophorin A (GPA) and up-regulated beta- and
gamma-globin by several fold. Both haemin and delta-ALA caused a de novo increase
in alpha-globin expression as well as enhancing Epo-induced beta-globin
expression, leading to a marked increase in haemoglobin production. These results
suggest that haemoglobin production in UT-7 cells is limited by a deficiency of
erythroid-specific aminolaevulinic acid synthase (ALAS-E) activity or globin
synthesis as a consequence of their immaturity as a multipotential cell line.
PMID- 10192448
TI - Diamond-Blackfan anaemia in the Italian population.
AB - Diamond-Blackfan anaemia (DBA) is a congenital disease characterized by defective
erythroid progenitor maturation: 30% of patients have congenital malformations.
The link between these malformations and defective erythropoiesis is unclear: a
defect in a molecule acting both on embryo development and haemopoiesis has been
proposed. Inheritance is autosomal dominant in most familial cases, but recessive
families have also been reported. Many cases are sporadic. A DBA locus has been
mapped on chromosome 19q13.2 (Gustavsson et al, 1997), but several families
unlinked to this locus have also been reported (Gustavsson et al, 1998). This
paper presents clinical, epidemiological and molecular data for DBA in the
Italian population. Segregation analysis of 19q markers in patients with DBA
showed exclusion of this locus in 5/12 families with inherited DBA. There was
evidently locus heterogeneity for DBA in this population. A new microdeletion was
identified in one patient. Other families, in which DBA segregates concordantly
with the 19q critical region, suggest incomplete penetrance and expressivity of
the DBA gene.
PMID- 10192449
TI - Three major G6PD-deficient polymorphic variants identified among the Mauritian
population.
AB - We report the results of the first epidemiological study investigating glucose 6
phosphate dehydrogenase (G6PD) deficiency among the heterogenous Mauritian
population. Mauritius has a population of approximately 1 million, and of these
66.8% are Indo-Mauritian (of Indian origin), 27.9% are Creoles (of African
ancestry) and 2.1% are Sino-Mauritian, predominantly of Chinese origin. Of the
1435 Mauritian males tested, 73 (5.1%) were G6PD deficient. However, the
prevalence varied considerably between the two major ethnic groups: 35/1157
(3.0%) for Indo-Mauritians and 37/267 (13.9%) for Creoles. Molecular analysis
revealed three major deficient polymorphic variants; G6PD Orissa, G6PD
Mediterranean and G6PD A-. G6PD Orissa (nt 131 G-->C; residue 44 Ala-->Gly) was
found to be the most common variant among Indo-Mauritians: this deficient variant
was recently identified to be highly characteristic of the tribal groups in
central India. In Creoles the most common deficient variant was G6PD A- (27/37).
These data are consistent with the different ancestral contributions to the
present gene pool of the Mauritian population. This study has provided further
information as to the precise nature of G6PD deficiency at the molecular level
among Indians, about whom previously there was scant information. The data
presented suggest that G6PD Orissa is widespread in central and southern states
of India. Additionally, the identification and frequency of G6PD-deficient
alleles in Mauritius is of public-health importance.
PMID- 10192450
TI - Mutation at position -12 of intron 45 (c-->t) plays a prevalent role in the
partial skipping of exon 46 from the transcript of allele alphaLELY in erythroid
cells.
AB - Allele alphaLELY is a common low-expression allele of the erythroid spectrin
SPTA1 gene. It results in the aggravated expression of hereditary elliptocytosis
due to SPTA1 gene mutations occurring in trans. Allele alphaLELY contains, in
particular, mutations in introns 45 and 46, both in polypyrimidine tracts, and
causes the partial skipping of exon 46. The corresponding six amino acids belong
to the nucleation site where the dimerization process of spectrin begins. In this
work we investigated the cause of exon 46 partial skipping. We made four types of
constructs with or without the intron 45 mutation, and with or without intron 46
mutation. Intron 45 mutation by itself dramatically triggered partial skipping of
exon 46. Intron 46 mutation had no effect by itself. It was not possible to
assess whether it modulated, even to a very small extent, the activity of intron
45 mutation. Taken together, intron 45 mutation is the prevalent, if not the
exclusive, determinant of the partial skipping of exon 46 in the transcript of
allele alphaLELY.
PMID- 10192451
TI - Mapping the prevalence of sickle cell and beta thalassaemia in England:
estimating and validating ethnic-specific rates.
AB - A range of estimates for sickle cell and beta thalassaemia have been derived for
the different ethnic groups living in the U.K., reflecting uncertainty over the
true population value in certain countries and the heterogeneity within and
between countries of origin comprising the same ethnic group. These were
validated against six community screening programmes, with the estimated range
correctly predicting the number of affected births observed by the programmes. In
England approximately 3000 affected babies (0.47%) carry sickle cell trait and
2800 (0.44%) carry beta thalassaemia trait annually: with approximately 178 (0.28
per 1000 conceptions) affected by sickle cell disease (SCD) and 43 (0.07 per
1000) by beta thalassaemia major/intermedia. Allowing for termination, about 140
175 (0.22-0.28 per 1000) affected infants are born annually with SCD and from 10
to 25 (0.02-0.04 per 1000) with beta thalassaemia major/intermedia. These are the
first evidence-based rates for sickle cell and beta thalassaemia for use in the
U.K., and should underpin the future planning of services. The long-term solution
to monitoring changes in the rates of trait and disease in the population is to
introduce a standardized instrument for collecting ethnicity for all community
screening programmes.
PMID- 10192452
TI - Red cell deformability in oral contraceptive pill users with sickle cell anaemia.
AB - The use of the combined oral contraceptive pill (COCP) in women with sickle cell
anaemia (SCA) is controversial, as contraceptive steroids are thought to
adversely affect erythrocyte deformability. This observational study was
performed to investigate whether hormonal contraception influenced erythrocyte
deformability in women with SCA. 30 women with SCA using various contraceptive
modalities: COCP (n = 10); progestogen only (PO) contraception (n = 10) and non
hormonal contraception (n = 10) were recruited. Erythrocyte deformability was
assessed using the clogging rate (CR) and red cell transit time (RCTT). There was
no statistical difference in the mean CR and RCTT between the three groups of
women (one-way ANOVA). Current contraceptive steroids do not appear to impair red
cell deformability in women with SCA.
PMID- 10192453
TI - Up-regulation of adhesion and MHC molecules on splenic monocyte/macrophages in
adult haemophagocytic syndrome.
AB - Haemophagocytic syndrome (HPS) has been associated with the abnormal activation
of mono/macrophages and increased cytokine production. However, neither the
phenotype of haemophagocytic monomacrophages nor the cellular origin of cytokine
production have been described. We studied splenic monomacrophages and
lymphocytes from five patients with HPS (two HIV- and three HIV+) and from
controls without HPS (three normal HIV and two pathological HIV+). Using flow
cytometry, we observed a marked increase in the expression of MHC class I and II,
M-CSF-receptor and adhesion molecules LFA-1, LFA-3, ICAM-1 (P<0.05) on HPS+
splenic monomacrophages compared to HPS-, which was independent of their HIV
status. A high percentage of CD8+ lymphocytes from 4/5 HPS+ patients produced TNF
alpha and IFNgamma, but no IL-6 upon in-vitro activation. In a fifth patient CD4+
but not CD8+ lymphocytes produced these cytokines. Although other cytokines might
be involved in the pathophysiology of HPS as suggested by the high expression of
M-CSF-receptor, these results suggest that TNF alpha and IFNgamma secretion by T
cells might play a role in the up-regulation of adhesion and MHC molecules on
monomacrophages from HPS.
PMID- 10192454
TI - Pregnancy-associated autoimmune neonatal thrombocytopenia: role of maternal HLA
genotype.
AB - In a prospective study between 1993 and 1998, data was collected from 46 pregnant
women and subsequently from their babies. 25 pregnant women with active
autoimmune thrombocytopenic purpura (AITP) or a history of AITP (group A) and 21
pregnant women with isolated thrombocytopenia and identification of specific
platelet autoantibodies detected by monoclonal antibody-specific immobilization
of platelet antigens (MAIPA) assay (group B) were evaluated for platelet
associated immunoglobulin-G (PAIgG), MAIPA assay and HLA genotype. Neonatal
platelet counts were performed at least three times in the first week. 11
neonates were thrombocytopenic (23.9%). No severe haemorrhage occurred. There
were no significant differences regarding the values of PAIgG or positive MAIPA
tests between mothers of thrombocytopenic or healthy newborns. A significant
difference, however, regarding the HLA DRB3* allele was found, with a high
incidence in the subgroup of mothers of healthy newborns (P = 0.005). A similar
trend was found among mothers with anti-GPIIbIIIa antibodies (P = 0.06). In
contrast, HLA DRB5* allele appeared to be present especially in mothers of
thrombocytopenic newborns (not significant). Our data suggest that mothers with
AITP who have the HLA DRB3* genotype are unlikely to give birth to a
thrombocytopenic baby. This study provides a preliminary report on a noninvasive
test to identify infants who are likely to be affected.
PMID- 10192455
TI - Studies of platelet volume, chemistry and function in patients with essential
thrombocythaemia treated with Anagrelide.
AB - Anagrelide (imidazoquinazolin derivative) is a new compound proposed for the
treatment of myeloproliferative disorders. In this study, Anagrelide was given to
patients with essential thrombocythaemia (ET) in a compassionate-use protocol.
The aim of this study was to test the effect of this drug not only on the
platelet count but also on platelet volume, chemistry and function, which has not
previously been reported. Thus, in ET, different functional or structural
platelet abnormalities were reported: a shortening of the bleeding time,
hypoaggregation to several agonists, and in particular a lack of response to
adrenalin, an increase in the amount of total platelet glycoprotein IV (or CD36),
and an abnormal migration of thrombospondin on electrophoresis. These different
parameters were studied before and during therapy with Anagrelide. Although the
platelet count was corrected, no functional or chemical abnormality was improved.
Furthermore, platelet volume was shown to be constantly increased under
Anagrelide. Thus, Anagrelide, in reducing the platelet count, may possibly
decrease the risk of thrombosis and haemorrhage. Nevertheless, if the risk of
thromboses and/or myelofibrosis is related not only to the platelet count but
also to the platelet abnormalities, the persistence of a thrombocytopathy in
patients treated with Anagrelide must be taken in consideration. Our data suggest
that thromboses and myelofibrosis are clinical end-points which should be
included in future large-scale use of Anagrelide.
PMID- 10192456
TI - Detection of lymphocytes and granulocytes expressing the mutant WASP message in
carriers of Wiskott-Aldrich syndrome.
AB - Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disease caused by
mutations in the recently identified WAS protein gene (WASP). In some X-linked
genetic disorders skewed X-inactivation has been observed in all cell populations
or some specific cell lineages of female carriers. Recently, female carriers of
WAS were also revealed to present skewed X-inactivation patterns at the
haemopoietic stem cell level. However, it is not clear if all haematological
cells expressing the mutant WASP allele are eliminated in WAS carriers. By
reverse transcription PCR methods, we studied 14 WAS carriers from 10 different
families to assess whether blood cells expressing the mutant WASP message were
present in their peripheral blood. The mutations of each WAS patient were known
and carrier diagnosis of their female family members was performed using specific
mutation analysis. We detected circulating lymphocytes and granulocytes
expressing the mutant WASP message in most of the WAS carriers, nevertheless they
showed skewed X-chromosomal inactivation patterns. Interestingly, the presence of
blood cells expressing the mutant WASP message seemed to correlate to the WASP
genotype and the age of the carriers.
PMID- 10192457
TI - The role of plasminogen activator inhibitor-1 as inhibitor of platelet and
megakaryoblastic cell adhesion.
AB - In the present study the ability of plasminogen activator inhibitor type-1 (PAI
1) to interfere with platelet and megakaryoblastic cell adhesion was
investigated. Both cell types exhibited integrin-dependent adhesion in a static
system, mediated by alphaIIb beta3 on platelets and alpha v-integrins on
different megakaryoblastic cell lines, even though they also expressed alphaIIb
beta3. In a concentration-dependent manner, active, but not latent or complexed,
PAI-1 abrogated cell adhesion onto vitronectin but not onto fibrinogen or other
matrix substrata. Urokinase as well as thrombin neutralized the anti-adhesive
effect of active PAI-1. The direct binding of vitronectin, but not of other
matrix proteins, to integrin alphaIIb beta3 was blocked by active PAI-1 in a
purified system. Since activated platelets release active and latent PAI-1 as
well as structurally and functionally distinct forms of vitronectin, the
described interactions appear to be physiologically significant. Co-distribution
of vitronectin and PAI-1 at sites of fibrin polymers within platelet thrombi was
demonstrated by transmission electron microscopy, suggesting an extracellular
functional relationship of both release products with regard to cell adhesion.
Our data emphasize the regulatory role of active PAI-1 in platelet adhesion to
provisional matrix proteins as found during wound healing independent of its anti
proteolytic activity. Furthermore, megakaryocyte maturation may depend on the
intact vitronectin-integrin adhesion system that is influenced by PAI-1, thereby
proposing a regulatory role for the inhibitor in cellular differentiation.
PMID- 10192458
TI - Factor VIII inhibitors in haemophiliacs: a single-centre experience over 34
years, 1964-97.
AB - A retrospective study of the natural history of factor VIII inhibitors in
haemophilia A patients experienced in a single comprehensive haemophilia centre
over three decades is reported. 431 haemophilia A patients of all severities have
been followed-up for a total of 5626 patient-years. The frequency of inhibitors
was 10% in the severe haemophilia A patients and 37% occurred in children <10
years. The majority of the patients received several products before developing
the inhibitors. 59% of patients had <50 exposure days and 48% were high
responders (>5 BU). An 8-year (1987-95) inhibitor-free period was seen during
which all previously untreated patients were treated with an intermediate-purity
factor VIII concentrate. A moderate haemophiliac with a missense mutation that
has not been described in association with inhibitor is reported. Six HIV
positive patients preserved their antibody response to factor VIII even at the
advanced stage of their disease.
PMID- 10192459
TI - A rapid method for haemophilia B mutation detection using conformation sensitive
gel electrophoresis.
AB - Conformation sensitive gel electrophoresis (CSGE) was confirmed as an effective
procedure for screening the factor IX (FIX) gene by detecting 10/10 previously
known FIX gene mutations. The FIX genes of a further 11 haemophilia B patients
with unknown mutations were then screened and an abnormal CSGE profile was
identified in all cases. Subsequent DNA sequencing demonstrated one of these to
be a novel mutation (31133insT, Arg338Fs), the remaining 10 having been
previously reported on the haemophilia B database. Mutation screening of the FIX
gene using CSGE was demonstrated to be a rapid and efficient means of carrier
analysis in families with haemophilia B.
PMID- 10192460
TI - Antibody-mediated inhibition of the human alloimmune response to platelet
transfusion in Hu-PBL-SCID mice.
AB - Severe combined immune deficient (SCID) mice were engrafted with human (Hu)
peripheral blood lymphocytes (PBL) from a previously alloimmunized donor and
transfused with HLA-mismatched platelets. We have previously shown this to be a
useful model for platelet transfusion. These engrafted mice (Hu-PBL-SCID mice)
produced high levels of alloantibody in response to standard platelet
preparations. However, when the first platelet challenge was presensitized with
anti-HLA antibody and then transfused there was a marked reduction in the amount
of alloantibody produced to five subsequent untreated platelet transfusions.
Platelets pretreated with platelet-specific anti-HPA-1a (PL(A1)) sera did not
induce a decrease in the anti-HLA alloantibody response. This demonstrated that
platelet-induced HLA alloimmunization can be blocked by anti-HLA antibody
sensitized cells.
PMID- 10192461
TI - Haematological parameters of parvovirus B19 infection in 13 fetuses with hydrops
foetalis.
AB - Thirteen cases of fetal parvovirus B19 infection with hydrops foetalis are
reported. Viral DNA was identified by polymerase chain reaction (PCR) of amniotic
fluid sampled between the 19th and the 29th week of gestation. Haematological
examination revealed severe anaemia in all cases and thrombocytopenia in 11/13
cases, which was severe in two cases. Six fetuses died in utero; two after
intrauterine transfusion. Complete recovery was observed in seven fetuses; five
cases were treated by intrauterine transfusions, and in two cases spontaneous
recovery occurred. Upon follow-up, no case of congenital anaemia was observed.
PMID- 10192462
TI - The interaction between Gilbert's syndrome and G6PD deficiency influences
bilirubin levels.
PMID- 10192463
TI - Low-risk essential thrombocythaemia in patients younger than 40.
PMID- 10192464
TI - Overwhelming septicaemia in a patient with sickle cell/beta(0) thalassaemia and
partial splenectomy.
PMID- 10192465
TI - Donor lymphocyte infusion as therapy for pure red cell aplasia following bone
marrow transplantation.
PMID- 10192466
TI - Human herpesvirus 8 infection, Castleman's disease and POEMS syndrome.
PMID- 10192467
TI - Cladribine for Waldenstrom's macroglobulinaemia.
PMID- 10192468
TI - Human herpesvirus 7 and lymphocytic leukaemia.
PMID- 10192469
TI - Refractory anaemia with excess of blasts in transformation (RAEB-T) during
pregnancy with haematological remission following delivery.
PMID- 10192470
TI - The distribution of sugar chains on the vomeronasal epithelium observed with an
atomic force microscope.
AB - The distribution of sugar chains on tissue sections of the rat vomeronasal
epithelium, and the adhesive force between the sugar and its specific lectin were
examined with an atomic force microscope (AFM). AFM tips were modified with a
lectin, Vicia villosa agglutinin, which recognizes terminal N-acetyl-D
galactosamine (GalNAc). When a modified tip scanned the luminal surface of the
sensory epithelium, adhesive interactions between the tip and the sample surface
were observed. The final rupture force was calculated to be approximately 50 pN
based on the spring constant of the AFM cantilever. Distribution patterns of
sugar chains obtained from the force mapping image were very similar to those
observed using fluorescence-labeled lectin staining. AFM also revealed
distribution patterns of sugar chains at a higher resolution than those obtained
with fluorescence microscopy. Most of the adhesive interactions disappeared when
the scanning solution contained 1 mM GaINAc. The adhesive interactions were
restored by removing the sugar from the solution. Findings suggest that the
adhesion force observed are related to the binding force between the lectin and
the sugars distributed across the vomeronasal epithelium.
PMID- 10192472
TI - The perceived intensity of caffeine aftertaste: tasters versus nontasters.
AB - The length and intensity of the aftertaste of caffeine was measured in groups of
tasters and nontasters in order to determine if any differential information
could be provided by aftertaste perception. Results indicate that a period of 4
min is sufficient to see differences between tasters and nontasters, and that
nontasters' aftertaste of the saturated solution is equal in intensity with
tasters perception immediately after stimulus presentation, but then after
approximately 1 min fade faster. Nontaster ratings for the weaker solution were
lower throughout the entire time period.
PMID- 10192471
TI - The effects of beta-bungarotoxin on the morphogenesis of taste papillae and taste
buds in the mouse.
AB - Although it has been long accepted that innervation by a taste nerve is essential
for maintenance of taste buds, it is not clear what role, if any, innervation
plays in the morphogenesis of taste papillae and taste bud development. The
following study was undertaken to determine what effects lack of sensory
innervation have on the development of taste papillae and the formation of taste
buds in the mouse. Timed-pregnant female mice (n = 3) at gestational day 12
(gd12) were anesthetized and a 1 microl solution (1 microg/microl) of beta
bungarotoxin (beta-BTX), a neurotoxin that disrupts sensory and motor neuron
development, was injected into the amniotic cavity of two embryos per dam. Two
shams were injected with PBS. Fetuses were harvested at gd18, 1 day before birth,
and four beta-BTX-injected embryos, two shams and two controls were fixed in
buffered paraformaldehyde. Serial sections were examined for the presence and
morphology of taste papillae and taste buds. No nerve profiles were observed in
beta-BTX-injected tongues. Although circumvallate papillae were present on beta
BTX tongues, only five fungiform papillae could be identified. Taste buds were
present on a large percentage of fungiform papillae profiles (24%) and on
circumvallate papillae in sham and control fetuses; in contrast, no taste buds
were associated with taste papillae in beta-BTX fetuses. These results implicate
a significant role for innervation in taste papillae and taste bud morphogenesis.
PMID- 10192473
TI - Taste qualities of solutions preferred by hamsters.
AB - Molecules of diverse chemical structure are sweet to humans and several lines of
evidence (genetic, physiological, behavioral) suggest that there may be distinct
sweet perceptual qualities. To address how many perceptual categories these
molecules elicit in hamsters (Mesocricetus auratus), we studied patterns of
generalization of conditioned taste aversions for seven sweeteners: 100 mM
sucrose, 320 mM maltose, 32 mM D-phenylalanine, 3.2 mM sodium saccharin, 16 mM
calcium cyclamate, 10 mM dulcin and 32 mM sodium m-nitrobenzene sulfonate. Each
stimulus was preferred versus water in two-bottle intake tests and stimulated the
chorda tympani nerve. For each of seven experimental groups the conditional
stimulus (CS) was a sweetener and for the control group the CS was water.
Apomorphine.HCl was injected i.p. after a CS was sampled and, after recovery,
test stimuli (TS) were presented for 1 h daily. The intake (ml) of each TS
consumed by experimental animals was compared with mean TS intake by the control
group. Learned aversions for 18/21 stimulus pairs cross-generalized, resulting in
a single cluster of generalization patterns for the seven stimuli. Cross
generalization failures (maltose-cyclamate, maltose-sucrose, cyclamate-NaNBS) may
be the consequence of particular stimulus features (e.g. salience, cation taste),
rather than the absence of a 'sucrose-like' quality. The results are consistent
with a single hamster perceptual quality for a diverse set of chemical structures
that are sweet to humans.
PMID- 10192474
TI - NMDA and non-NMDA receptors mediate responses in the primary gustatory nucleus in
goldfish.
AB - Primary gustatory afferents from the oropharynx of the goldfish, Carassius
auratus, terminate in the vagal lobe, a laminated structure in the dorsal medulla
comparable to the gustatory portion of the nucleus of the solitary tract in
mammals. We utilized an in vitro brain slice preparation to test the role of
different ionotropic glutamate receptor subtypes in synaptic transmission of
gustatory information by recording changes in field potentials after application
of various glutamate receptor antagonists. Electrical stimulation of the vagus
nerve (NX) evokes two short-latency postsynaptic field potentials from sensory
layers of the vagal lobe. 6,7-Dinitroquinoxaline-2,3-dione and 6-nitro-7
sulphamoylbenzo[f]quinoxaline-2,3-dione, two non-N-methyl-D-aspartate (NMDA)
ionotropic receptor antagonists, blocked these short-latency potentials. Slower
potentials that were revealed under Mg2+ -free conditions, were abolished by the
NMDA receptor antagonist, D(-)-2-amino-5-phosphonovaleric acid (APV). Repetitive
stimulation produced short-term facilitation, which was attenuated by application
of APV. These results indicate that the synaptic responses in the vagal lobe
produced by stimulation of the gustatory roots of the NX involve both NMDA and
non-NMDA receptors. An NMDA receptor-mediated facilitation may serve to amplify
incoming bursts of primary afferent activity.
PMID- 10192475
TI - Neonatal atrial flutter following fetal exposure to vibroacoustic stimulation.
AB - The use of vibroacoustic stimulation (VAS) has become a common modality for
testing fetal well being. A case of neonatal atrial flutter, following fetal
exposure to VAS is presented. It should be emphasized that although VAS is a
common and reliable test for evaluating fetal status, complications may occur.
PMID- 10192476
TI - Ultrasound-guided fine needle aspiration of ovarian cysts during pregnancy.
AB - OBJECTIVE: To evaluate the safety and efficacy of ultrasound-guided fine needle
aspiration in the treatment of ovarian cysts during pregnancy. STUDY DESIGN: Nine
out of twenty-nine patients between the 6th and the 16th week of gestation with
unilateral ovarian cysts ranging between 65 and 540 cm3 in volume were selected
for sonographically-guided fine needle aspiration. RESULTS: No complications were
observed at either short or long-term follow-up; all patients delivered healthy
infants at term. Clinical and sonographic post-partum follow-up was uneventful in
all cases. In three cases it was necessary to repeat the procedure once and in
one case twice during pregnancy. In one case a recurrent serous cyst was excised
at operative laparoscopy performed 3 months after delivery. CONCLUSIONS:
Ultrasound-guided fine needle aspiration was safely performed in nine patients as
an alternative treatment to surgery when persistent monolateral and unilocular
ovarian cysts with regular borders and completely anechoic structure are detected
during pregnancy.
PMID- 10192477
TI - Umbilical and middle cerebral artery Doppler indices in patients with
preeclampsia.
AB - OBJECTIVE: To compare changes in Doppler ultrasound studies of fetal circulation
in normal pregnancies with those of a group of preeclamptic patients both with
and without intrauterine growth retardation and to demonstrate the best index for
predicting adverse perinatal outcome or IUGR. STUDY DESIGN: A cross-sectional
study was performed on 125 normal pregnancies and 62 preeclamptic patients at 31
40 weeks of gestation. The umbilical artery systolic-diastolic ratio (UA S/D), UA
pulsatility index (PI), the middle cerebral artery (MCA) PI, and the ratio of MCA
PI to UA PI were measured. The mean values of the Doppler indices were compared.
Different cut-off values (mean +/-2 S.D.) were used for the 31st-35th and the
36th-40th weeks. RESULTS: Significant differences were found between normal
pregnancies and preeclamptic patients without IUGR using the mean MCA PI and the
MCA PI/UA PI ratio. In the preeclamptic patients with IUGR, all the mean Doppler
indices were different from those of the normal pregnancies. In the preeclamptic
patients with IUGR the values were different from the preeclamptic patients
without IUGR, except for the MCA PI at 31-35 weeks. The UA S/D had the highest
sensitivity (88%) and diagnostic accuracy (94%) in predicting the adverse
perinatal outcome. The MCA PI/UA PI ratio showed the highest predictive value in
determining IUGR by a sensitivity of 84% and a diagnostic accuracy of 87%.
CONCLUSION: Both abnormal umbilical Doppler indices and cerebral-umbilical ratio
are strong predictors of IUGR and of adverse perinatal outcome in preeclampsia.
The MCA PI alone is not a reliable indicator. The combination of umbilical and
fetal cerebral Doppler indices may increase the utility of Doppler ultrasound in
preeclamptic subjects.
PMID- 10192478
TI - Bartter's syndrome and pregnancy.
AB - Bartter's syndrome is a rare renal tubular disorder and few cases are reported
associated with pregnancy. We describe a case of long standing disease with a
good obstetric outcome in which the main concern was to maintain normal potassium
serum levels.
PMID- 10192479
TI - Omphalocele delivery enigma: the best mode of delivery still remains dubious.
AB - OBJECTIVE: To determine an optimal route of delivery for fetuses with prenatally
diagnosed omphalocele. DATA SOURCE: MEDLINE search of years 1966-1996. RESULTS:
Descriptive retrospective analyses do not support the idea that cesarean delivery
of fetuses with omphalocele is associated with an improved survival rate.
However, most of those studies do not control for confounding variables like type
and severity of associated anomalies, omphalocele size, prematurity rate,
presence of trial of vaginal delivery, rate of intrapartum sac rupture, tertiary
treatment centers accessibility, time and type of surgical correction, and
postoperative morbidity. There is no evidence that vaginal delivery is safer than
cesarean for fetuses with isolated small omphalocele. Fetuses with giant (>5 cm)
omphalocele should be delivered by cesarean section. Vaginal delivery at term is
offered for fetuses with coexisting life-threatening anomalies. CONCLUSIONS: We
propose that until randomized trial of vaginal and cesarean delivery for fetal
omphalocele is available, the preferred mode of delivery would be the vaginal
route as that is safer for the mother.
PMID- 10192480
TI - Lymphocyte subpopulations in intrauterine growth retardation in women with or
without previous pregnancies.
AB - OBJECTIVE: To evaluate lymphocyte subpopulations in pregnant women with
intrauterine growth retardation (IUGR). STUDY DESIGN: Forty-two normotensive and
healthy women with singleton pregnancies and intrauterine growth retardation were
studied in the third trimester of pregnancy and compared with 42 normal pregnant
women. Peripheral blood lymphocytes were studied using murine monoclonal
antibodies and flow cytometry. RESULTS: B-lymphocytes in both total number
(312.54 vs. 163.19 cells/mm3; P = 0.000003) and percentage (11.04% vs. 7.07%; P =
0.000002) were significantly increased in patients with IUGR in comparison to
normal pregnant women. Significant correlations were found between birthweight
and both total number and percentage of lymphocytes B. In primigravid women, we
found that women with IUGR had a higher total lymphocyte count (2749.09 vs. 2130
cells/mm3; P = 0.006), higher T-lymphocyte count (2053.77 vs. 1676.40 cells/mm3;
P = 0.02), higher B-lymphocyte count and percentage (309.13 vs. 145.36 cells/mm3;
P = 0.000001) (11.45 vs. 6.81%); P = 0.00001), higher CD4 lymphocyte count and
percentage (1342.68 vs. 972.22 cells/mm3, P = 0.001) (49.18 vs. 44.04%; P =
0.04), lower CD8-lymphocytes percentage (28.27 vs. 32.9%; P = 0.04), and higher
CD4/CD ratio (1.83 vs. 1.46; P = 0.02) than the normal control group.
CONCLUSIONS: B-lymphocytes are increased in women with IUGR in comparison to
women with normal pregnancies and there was a significant negative correlation
between maternal B-lymphocytes and birthweight. With respect to T-lymphocytes,
the immunological profile is different according to the presence or absence of a
previous pregnancy. Fetal immunological rejection could be involved in the
pathogenesis of IUGR in primigravid women, but in multigravid women there were no
differences between women with IUGR and those with normal fetal growth.
PMID- 10192481
TI - Amnioinfusion in term labor with low amniotic fluid due to rupture of membranes:
a new indication.
AB - OBJECTIVE: The null hypothesis was that the use of intrapartum amnioinfusion to
induce term labor because of premature rupture of membranes when labor was
complicated by low amniotic fluid volume due to vaginal loss would not improve
fetal heart rate patterns, decrease the incidence of operative delivery, or
improve neonatal acid-base status. STUDY DESIGN: 200 term pregnancies with low
amniotic fluid due to vaginal loss were randomly chosen to receive intrapartum
amnioinfusion or standard obstetric care without amnioinfusion. Fetal heart rate
pattern, method of delivery and neonatal acid-base status were compared with
Student's t test, chi-squared analysis, Mann-Whitney U- or Fisher's exact test.
RESULTS: When amnioinfusion was used, the fetuses had lower rates of variable (74
vs. 91%, P<0.01) or late (26 vs. 58%, P<0.001) decelerations. Spontaneous
deliveries were more frequent (77 vs. 59%, P<0.01) and cesarean sections less
frequent (3 vs. 10%, P<0.05). Mean umbilical arterial (7.24+/-0.07 vs. 7.21+/
0.08, P<0.01) and venous (7.31+/-0.06 vs. 7.28+/-0.08, P<0.01) pH were
significantly higher in newborns with amnioinfusion, and babies in this group had
lower rates of neonatal acidemia of arterial (22 vs. 36%, P<0.005) or venous (13
vs. 26%, P<0.005) origin. CONCLUSIONS: Amnioinfusion improved fetal heart rate
pattern, lowered the incidence of operative delivery, and improved neonatal acid
base status in term labor complicated by low amniotic fluid due to vaginal loss.
PMID- 10192482
TI - Nitric oxide metabolites, cyclic guanosine 3,5 monophosphate and
dimethylarginines during and after uncomplicated pregnancies: a longitudinal
study.
AB - OBJECTIVE: In cross-sectional studies, the variability between women may mask or
deny gestational changes, related to the nitric oxide-cyclic GMP system.
Therefore, we analyzed longitudinally as markers of this system, the urinary
levels of nitrite+nitrate (NOx), cyclic guanosine 3',5' monophosphate (cGMP) and
of the inhibitor of nitric oxide synthase, dimethylarginine (DMA). STUDY DESIGN:
Late-afternoon urine samples were obtained from 20 women with uncomplicated
pregnancies and nine non-pregnant women. Creatinine concentrations (mol) were
determined with the Jaffe reagent and NOx (mmol) with the Griess reagent after
reduction of nitrate. cGMP (micromol) was determined in an enzyme immunoassay and
DMA (mmol) after solid-phase extraction and liquid chromatography. Trend analyses
and (paired) t-tests were done for detection of time-related differences.
RESULTS: The NOx/creatinine (mmol/mol) ratios of the non pregnant women (63.8+/
18.8, S.D.) did not differ from those of the pregnant women at the onset of
pregnancy (70.5+/-36.4). Over the entire pregnancy period these ratios declined
significantly (P<0.001) and lower values were found at the end of gestation and
after birth (49.6+/-22.4). The cGMP/creatinine (micromol/mol) and DMA/creatinine
ratios (mmol/mol) changed parabolically (P<0.001). The maxima of 68.0+/-19.9 and
of 4.95+/-1.01 were found at week 20 and 16, respectively. These ratios declined
to 45.2+/-17.7 and to 4.03+/-0.83 at the end of gestation but not further during
parturition (39.6+/-17.2 and 4.01+/-1.90). The lowest cGMP/creatinine ratios
occurred one month after birth (27.4+/-15.7) while in the non-pregnant women the
value was 15.3+/-6.2 microM/M. The lowest DMA/creatinine ratios, measured one
month after birth (3.41+/-1.28 mmol/mol) were similar to those of the non
pregnant women (3.75+/-0.39 mmol/mol). Positive instead of negative relationships
were found between the DMA results and those of the cGMP (P<0.001) and NOx
determinations (P<0.05). CONCLUSIONS: (1) The gestational changes of the urinary
NOx/creatinine and especially of the GMP/creatinine ratio reflect most likely
changes in vascular resistance. (2) Because of the variability of the results
between but also within women, these ratios are useless to monitor supposed
changes in NO production during parturition.
PMID- 10192483
TI - Pre-eclampsia and the HELLP syndrome still cause maternal mortality in The
Netherlands and other developed countries; can we reduce it?
AB - Maternal mortality in developed countries does not seem to have decreased during
the past decade, despite good prenatal care. Hypertensive disorders of pregnancy
are the main cause of maternal mortality in most countries. In more than half of
these cases, the HELLP syndrome is involved. In this article attention is drawn
again to the life-threatening complications that might occur in cases of pre-
eclampsia and the HELLP syndrome. Two case histories with fatal outcomes are
described to provide extra emphasis. The literature indicates that some cases of
maternal mortality might be avoidable. From a review of the literature,
suggestions and recommendations are made about how to achieve a decrease in
maternal mortality from pre-eclampsia/the HELLP syndrome. The most important are
the making of an early, correct diagnosis, anticipating the possibilities of
serious complications, and, if necessary, early referral to a regional centre
with special expertise.
PMID- 10192484
TI - Placental aging, fetal prognosis and fetomaternal Doppler indices.
AB - OBJECTIVE: To investigate the possible effects of the morphological changes in
the placenta on fetal prognosis and on umbilical artery and uterine artery
Doppler indices in late, low-risk pregnancies. STUDY DESIGN: Placental changes
were evaluated ultrasonographically and pathologically in 224 pregnant women
after the 25th gestational week. The placental morphology were graded
ultrasonographically into five subgroups according to increasing severity of the
changes. Postnatally, the neonate was examined, Apgar scores, and adverse events
if any, were noted. Placentas with infarction, decidual necrosis, ischemic
villitis, chorioangioma, placenta previa or placental abruption and high risk
pregnancies were excluded. RESULTS: There were 21, 38, 52, 56 and 57 cases in
grades I, II, III, IV, and V respectively. Apgar scores of the babies in all
placental grades were similar (P>0.05). In all cases, Doppler indices of both
uterine and umbilical artery were within normal limits. No significant
association between placental morphological characteristics and Doppler indices
of either uterine or umbilical arteries could be demonstrated. There was no
correlation between Apgar scores and morphological characteristics of the
placenta or Doppler indices. CONCLUSIONS: Morphological changes of placental
aging are common and seem to have no effect on fetus and on Doppler flow of the
umbilical and uterine arteries, provided these are not high-risk pregnancies and
placental changes are not infarction, villitis or severe structural or
localization anomaly.
PMID- 10192485
TI - Lipid and lipoprotein cardiovascular risk factor changes during normal pregnancy
in Africans.
AB - OBJECTIVES: The study was designed to determine how pregnancy affects lipid and
lipoprotein profiles among women living in a typical suburban commercial
community in Africa, and to highlight the consequences of such changes. STUDY
DESIGN: Lipid and lipoprotein levels and coronary heart disease (CHD) risk
predictor index [High density lipoprotein-cholesterol (HDLC)/Total cholesterol
(TC)] were evaluated in 27 African pregnant and 17 non-pregnant women of the same
age and demographic profiles. RESULTS: Total cholesterol and low density
lipoprotein-cholesterol (LDLC) levels increased, while HDLC level and HDLC/TC
ratio decreased in the pregnant women. CONCLUSIONS: These findings suggest that
African women are more prone to hyperlipidemia during normal pregnancy. The
consequences of the adverse lipid and lipoprotein changes as seen in the pregnant
women, on the fetal development and welfare should be explored in further
studies. In general, these results have added to our understanding and knowledge
of the numerous factors that could cause abnormal lipid and lipoprotein levels in
African women.
PMID- 10192486
TI - Limitations of the evaluation of adnexal masses by its macroscopic aspects,
cytology and biopsy.
AB - To investigate the relevance of intraoperative macroscopic evaluation of adnexal
masses a prospective study was conducted from June 1st, 1993 to May 31st, 1994,
which included 57 premenopausal and 60 postmenopausal women, who underwent
laparotomy because of a cystic adnexal mass. The surgeons were asked to classify
the tumor intraoperatively as benign or malignant and to assign to histologic
groups. In addition cytology of the cyst fluid and a biopsy from the cystic wall
were evaluated. Comparison of these items with the results of permanent section
diagnosis revealed the tendency of the surgeons to underestimate adnexal masses
depending on patients' age and the complexity of the tumor, despite of the
knowledge of preoperative ultrasonographic findings. Sufficient cytolologic
examination was possible in only one third of aspirates and only 21% of the
examined postmenopausal malignant neoplasms have correctly been diagnosed by
cytology. Evaluation of the biopsy specimens demonstrates a marked percentage of
false negatives with respect to benign tumors (30% of non-functional benign
neoplasms in the premenopause were assessed as functional cysts) as well as
malignant neoplasms (only 72% were diagnosed correctly in the postmenopause
group). In conclusion intraoperative subjective assessment, cytology and
representative biopsies do not necessarily concur with the definitive
histological diagnosis.
PMID- 10192487
TI - Reproductive factors, family history, occupation and risk of urogenital prolapse.
AB - OBJECTIVE: We conducted a case-control study to analyze risk factors for
urogenital prolapse requiring surgery. METHODS: Cases were 108 women with a
diagnosis of II or III degree uterovaginal prolapse and/or third degree
cystocele. Controls were 100 women admitted to the same hospitals as the cases,
for acute, non-gynecological, non-neoplastic conditions. RESULTS: Occupation
showed an association with urogenital prolapse: in comparison with
professional/managerial women, housewives had an odds ratios (OR) of urogenital
prolapse of 3.1 (95% confidence interval (CI), 1.6-8.8). Compared with
nulliparae, parous women tended to have a higher risk of genital prolapse (OR
2.6, 95% CI 0.9-7.8). In comparison with women reporting no vaginal delivery, the
ORs were 3.0 for women reporting one vaginal delivery (95% CI 1.0-9.5), and 4.5
(95% CI 1.6-13.1) for women with two or more vaginal deliveries. Forceps delivery
and birthweight were not associated with risk of prolapse after taking into
account the effect of number of vaginal deliveries. The risk of urogenital
prolapse was higher in women with mother or sisters reporting the condition: the
ORs were, respectively, 3.2 (95% CI 1.1-7.6) and 2.4 (95% CI 1.0-5.6) in
comparison with women whose mother or sisters reported no prolapse. CONCLUSIONS:
Our data support the clinical suggestion that parous women are at a higher risk
of prolapse and the risk increases with number of vaginal deliveries. First
degree family history of prolapse seems to increase the risk of prolapse.
PMID- 10192488
TI - Joint hypermobility in African non-pregnant nulliparous women.
AB - OBJECTIVE: To investigate the prevalence of joint hypermobility in non-pregnant
nulliparous women and the influences of age and Quetelet-index in a rural, female
population in Tanzania. STUDY DESIGN: A cross-sectional study. Joint mobility was
measured according to the scoring systems of Beighton and Biro. RESULTS:
According to the Beighton criteria with a score of 0 to 9 points, 50.5% of 705
non-pregnant nulliparous women scored 3, while 30.8% scored > or =4 and 18.6% >
or =5. There were no correlations between hypermobility and age or Quetelet
index. The prevalence of hypermobility at the dominant body side was
significantly lower (19.2%) than at the non-dominant side (23.4%) (p<0.001).
CONCLUSION: This study confirms that there are ethnic differences in the
prevalence of hypermobility. The prevalence of hypermobility in Tanzanian non
pregnant nulliparous women is about 1.5-times higher as compared to Dutch non
pregnant nulliparous women. Prevalence of hypermobility was higher at the non
dominant body side. The most predictive test for the diagnosis of hypermobility
was the hyperextension of the elbows >10 degrees.
PMID- 10192489
TI - Clinical associations with objective menstrual blood volume.
AB - OBJECTIVE: To determine the association between simple clinical parameters and
objective menstrual blood volume. STUDY DESIGN: A cohort study, in a London
teaching hospital. Women complaining of menorrhagia (207) and those who
considered their menstruation to be normal (47) were studied. Those with no
demonstrable gynaecological pathology had their menstrual blood loss measured
using the alkaline haematin technique. RESULTS: Only 49% of 207 women complaining
of menorrhagia had a loss of 80 ml or more. There was an increasing incidence of
objective menorrhagia with increasing duration of bleeding and use of more
sanitary protection items. Increasing height, age and number of intrauterine
pregnancies were all associated with increasing menstrual blood volume.
Haemoglobin fell with increasing menstrual blood loss. CONCLUSIONS: Despite these
clinical associations it is difficult to establish the quantity of menstrual
bleeding with certainty without an objective assessment.
PMID- 10192490
TI - Neovagina with cultured allogenic epidermal sheets.
AB - Several materials have been used in neovagina construction, but most of them show
some kind of drawback. This is the report of a case in which cultured allogenic
epidermal sheets were used instead of skin grafting for a McIndoe procedure.
PMID- 10192491
TI - Brain metastasis as first manifestation of ovarian cancer.
AB - Brain metastasis from ovarian cancer, a rare and highly dismal event, develops
mostly during or after postoperative chemotherapy. This report documents the
clinical findings and magnetic resonance imaging of an uncommon case who
presented signs of increased intracranial pressure as a first manifestation.
Histologic examination of removed brain lesion demonstrated ovarian origin, while
no evidence of a locally invasive lesion was found at exploratory laparotomy
('tentative' surgical stage Ia). The possibility of ovarian origin should be
always considered in a woman with brain involvement.
PMID- 10192492
TI - Carcinosarcoma, endometrial intraepithelial carcinoma and endometriosis after
tamoxifen therapy in breast cancer.
AB - The fourth case of heterologous mesodermal tumour of the uterine corpus, that
developed, years following tamoxifen therapy for breast cancer in a
postmenopausal woman with no previous pelvic irradiation, is presented with
coincidental endometriosis and endometrial intraepithelial carcinoma. This
coincidence after tamoxifen treatment appears to be an indication for the
possible carcinogenic potency of tamoxifen.
PMID- 10192493
TI - Rapid progression of squamous cell carcinoma of the cervix after hyperbaric
oxygenation.
AB - The role of hyperbaric oxygenation in the treatment of radiation-induced sequelae
and chronic ulcer is well established. On the contrary, a possible cancer-causing
or growth-enhancing effect by hyperbaric oxygenation was highly controversial.
Herein, we present a 55-year-old Chinese woman with recurrent squamous cell
carcinoma of the cervix on her left inguinal area. She received concurrent
chemoradiation therapy followed by radical inguinal lymphadenectomy due to
persistent tumor mass. The patient was complicated with severe radiation fibrosis
and unhealed wounds, so she was treated with hyperbaric oxygenation (HBO).
However, the patient died of complications of the disease after completing HBO
therapy I month later and autopsy of the patient showed carcinomatosis of the
abdominal cavity and lower abdominal wall. Because previous studies have been
inconclusive regarding the effect of HBO on tumor cells, we reviewed the possible
relation between the HBO and tumor cells.
PMID- 10192494
TI - Dermatomyositis and peritoneal papillary serous carcinoma.
AB - We describe an unusual case of peritoneal papillary serous carcinoma (PPSC)
arising in a female patient with dermatomyositis (DM). Despite periodic extensive
searches for an underlying malignancy, no malignancy had been detected in this
patient during the first 2.5 years after the diagnosis of DM. It was only when
the patient presented with pleural effusion and ascites that the underlying intra
abdominal malignancy was detected by laparoscopy. Treatment with four cycles of
pre-operative chemotherapy (taxol and cisplatin) resulted in tumor regression
with amelioration in the muscular manifestation of the DM, but without parallelic
amelioration in the skin manifestations of the DM. Explorative laparotomy
confirmed the presence of papillary serous carcinoma in the omentum, surface of
the left ovary and the retroperitoneal lymph nodes, and established the diagnosis
of PPSC. Following two cycles of postoperative chemotherapy, the patient is alive
with no evidence of internal malignancy. However, although muscle strength and
enzymes have remained normal, no effect on the skin manifestation of DM has been
observed. This case illustrates that, alongside the more frequently occurring
ovarian carcinoma, PPSC should also be considered in the differential diagnosis
of the underlying malignancy that may occur in the female patient with DM.
PMID- 10192495
TI - Meigs' syndrome with elevated CA125: case report and review of the literature.
AB - A 51-year-old woman presented with acute ascites and hydrothorax is reported.
Pelvic ultrasound showed two pelvic solid masses and serum CA125 level was
elevated (577 IU/ml). Pathology revealed bilateral ovarian fibromas. We present
this case of Meigs' syndrome and discuss its diagnostic problems and a review of
the literature.
PMID- 10192496
TI - Self-concept, body image, and use of unconventional therapies in patients with
gynaecological malignancies in the state of complete remission and recurrence.
AB - OBJECTIVE: Are there differences in self-concept and body image in patients with
cancer recurrence in comparison to patients with complete remission? What impact
has cancer recurrence on use, users and non-users of unconventional cancer
therapies? PATIENTS AND METHODS: One hundred and nine patients with no evidence
of disease after gynaecological cancer and sixty-one patients with recurrent
disease were analysed for self-concept with the Frankfurter Selbstkonzeptskalen
and body image with the Frankfurter Korperkonzeptskalen. Use and motivation for
unconventional therapies was assessed with a questionnaire. RESULTS: With respect
to frequency of use and expected benefits of unconventional therapies no
differences were observed between the groups. However, cancer recurrence was
found to induce considerable changes of self-concept and body image, some
indicating even positive changes due to cancer recurrence. CONCLUSION: It may be
beneficial to consider body therapy and psychotherapy as a mean to improve body
image and self-esteem in cases with cancer recurrence.
PMID- 10192497
TI - Serum C-reactive protein as a prognostic factor in patients with epithelial
ovarian cancer.
AB - OBJECTIVE: It is well known that the serum level of Interleukin-6 (IL-6)
correlates with the level of C-reactive protein (CRP). The purpose of this study
is to determine the significance of CRP as a prognostic factor in epithelial
ovarian cancer. STUDY DESIGN: The present study is comprised of 120 patients with
epithelial ovarian cancer from 1985 to 1992. In this study, CRP levels above 50
mg/l were considered high CRP. Univariate and multivariate analyses were
performed to identify clinicopathological variables associated with poor
survival. RESULTS: The serum CRP value was significantly associated with the
volume of ascites (P = 0.000004). Univariate analysis showed that the FIGO stage,
primary tumour diameter, size of residual tumour, histologic grade, volume of
ascites and high serum level of CRP were significant prognostic factors. Cox's
multivariate proportional hazard model showed that histologic grade was the most
important prognostic factor (P = 0.0026). FIGO stage and volume of ascites were
also independent factors for 5-year survival (P = 0.0310 and P = 0.0216,
respectively). However, the serum CRP value was not an independent prognostic
factor. CONCLUSION: CRP is an adverse prognostic factor in univariate analysis,
but not in multivariate analysis.
PMID- 10192498
TI - Eosinophil derived neurotoxin (EDN) levels in commercial human urinary
preparations of glycoprotein hormones.
AB - Eosinophil derived neurotoxin (EDN) is a ubiquitous human ribonuclease, occurring
not only in eosinophils, but also in many tissues and body fluids. It may be a
contaminant of commercial human urinary preparations of chorionic gonadotropin
(hCG) and other glycoprotein hormones. Here we describe the use of a fast
commercial assay to quantify this contaminant and demonstrate that the content
varies much between different commercial glycoprotein hormone preparations. As
this ribonuclease may have a cytotoxic activity on certain cells, it is useful to
be able to determine its quantity in a fast and reliable way in these
preparations.
PMID- 10192500
TI - The antiphospholipid syndrome and 'multiple sclerosis'.
PMID- 10192499
TI - The multi-faceted role of transforming growth factor-beta in systemic lupus
erythematosus.
PMID- 10192501
TI - The relationship between defects in lymphocyte production of transforming growth
factor-beta1 in systemic lupus erythematosus and disease activity or severity.
AB - Transforming growth factor beta (TGF-beta) comprises of a family of proteins with
pleiotropic signaling properties and potent immunoregulatory effects. In SLE we
recently reported that lymphocyte production of the total and active forms of TGF
beta1 was decreased. Here we asked whether these defects correlate with disease
activity and/or severity. TGF-beta1 production by blood lymphocytes from 17
prospectively studied SLE patients was compared with 10 rheumatoid arthritis (RA)
patients and 23 matched healthy controls. The RA levels of active TGF-beta1 were
lower than controls, but were not deceased to the extent found in SLE. Levels of
constitutive and anti-CD2 stimulated active TGF-beta1 detected in picomolar
amounts were markedly reduced in six untreated patients hospitalized with recent
onset, very active and severe SLE and similarly reduced in 11 patients with
treated, less active disease. By contrast, decreased production of total TGF
beta1 inversely correlated with disease activity. These studies suggest,
therefore, that although impaired lymphocyte secretion of the latent precursor of
TGF-beta1 may result as a consequence of disease activity, a decreased capacity
to convert the precursor molecule to its active form may pre-date disease onset.
Insufficient exposure of T cells to picomolar concentrations of TGF-beta1 at the
time they are activated can result in impaired down-regulation of Ig synthesis.
Therefore, decreased lymphocyte production of active TGF-beta1 in SLE could be an
immunologic defect which contributes to the B cell hyperactivity characteristic
of this disease.
PMID- 10192502
TI - Cytokine-mediated down-regulation of B cell activity in SLE: effects of
interleukin-2 and transforming growth factor-beta.
AB - We have recently reported that transforming growth factor-beta (TGF-beta) co
stimulates interleukin-2 (IL-2) activated CD8+ T cells to down-regulate antibody
production. In SLE, lymphocyte production of both IL-2 and TGF-beta is decreased.
Here we report that a brief treatment of PBMC from SLE patients with IL-2 and TGF
beta can result in marked inhibition of spontaneous polyclonal IgG and
autoantibody production. Peripheral blood mononuclear cells (PBMC) from 12
patients with active SLE were exposed to IL-2 with or without TGF-beta for three
days, washed and cultured for seven more days. The mean decrease in IgG secretion
was 79%. The strongest inhibitory effect was observed in cases with the most
marked B cell hyperactivity. Spontaneous production of anti-nucleoprotein (NP)
antibodies was observed in four cases and cytokine treatment of PBMC decreased
autoantibody production by 50-96%. IL-2 inhibited Ig production by either TGF
beta-dependent or independent mechanisms in individual patients. In a study of
anti-CD2 stimulated IgG production in a patient with active SLE, we documented
that IL-2 and TGF-beta reversed the enhancing effects of CD8+ T cells on IgG
production and induced suppressive activity instead. These results raise the
possibility that cytokine-mediated down-regulation of B cell hyperactivity in SLE
may have therapeutic potential.
PMID- 10192503
TI - Synergetic effect between interleukin-1 receptor antagonist allele (IL1RN*2) and
MHC class II (DR17,DQ2) in determining susceptibility to systemic lupus
erythematosus.
AB - We investigated whether IL1RN alleles separately or in combination with MHC class
II variants, contribute to susceptibility to SLE and to analysed if IL1RN alleles
are markers of disease severity. We investigated 81 patients from a defined area
in southern Sweden diagnosed between 1981-1992 and 10 consecutive Caucasian
families with multiple cases of SLE. As control group 189 healthy blood donors
was used. PCR amplification of defined gene sequences was used in determining the
IL1RN polymorphism as well as the MHC class II variants. The IL-1RA levels were
measured by an immunoassay. We found an increased frequency of IL1RN*2 in both
the epidemiological cohort and in the multicase families (P < 0.01). Alone
IL1RN*2 and MHC class II (DR17,DQ2) separately increased the SLE risk moderately.
The occurrence of IL1RN*2 and MHC class II variants DR17 and DQ2 together
increased the risk to develop SLE by a sevenfold. The IL-1RA gene polymorphism
did not correlate with disease severity or with renal involvement. We found an
association between IL1RN*1 and arthritis (P < 0.001). Serum level of IL-1RA did
not correspond to any specific IL1RN allele. An increased frequency of IL1RN*2
suggests the presence of a gene, implemented in SLE-susceptibility, in the IL1RN
region of chromosome 2. IL1RN*2 and specific variants of MHC class II act in
synergy to increase disease susceptibility. IL1RN*1 may be a marker of risk for
development of arthritis.
PMID- 10192504
TI - Anti-phospholipid antibodies in patients with multiple sclerosis and MS-like
illnesses: MS or APS?
AB - OBJECTIVE: To describe the frequency, clinical, and laboratory features of
patients diagnosed with multiple sclerosis (MS) or MS-like illnesses (MSL) among
a large, prospectively followed cohort of anti-phospholipid antibody (aPL)
positive patients. METHODS: Between 1990 and 1995 patients referred to a
university-affiliated rheumatology clinic were prospectively evaluated for aPL
based on questionnaires designed to detect aPL-related symptoms and/or a family
history of aPL-related illnesses. Magnetic resonance imaging (MRI) was performed
when significant neurological features were present. A subgroup of all patients
diagnosed with MS or MSL was identified and their clinical, laboratory, and
imaging findings were reviewed. RESULTS: Of 322 patients evaluated for aPL
related symptoms or events, 189 (59%) were positive for at least one class of
aPL. Twenty-six of 322 patients (8%) carried a diagnosis of MS or MSL, either at
the initial evaluation or during the study period. Twenty-three of the 26
individuals (88%) tested positive for aPL, while the remaining 3 (11%) tested
repeatedly negative. Eighteen of the 23 patients (78%) had either more than one
class of aPL or had multiple positive titers. IgM aCL was noted in 18 of the 23
patients (78%). Oligoclonal bands were noted in five patients. Antinuclear
antibodies (ANA) and low complement levels were frequently observed. Blinded MRI
readings showed lesions consistent with MS in the majority of cases. Clinically,
7 patients had transverse myelitis (TM), while optic neuritis (ON) was present in
8 patients. Most patients had either occult symptoms of rheumatic disease or
contributory family histories. None had a defined underlying connective-tissue
disease. CONCLUSION: A substantial number of aPL-positive patients have a
concurrent diagnosis of MS or MSL, frequently presenting with elevated IgM aCL,
optic neuritis, and transverse myelitis. The anti-phospholipid syndrome (APS)
should be strongly considered as an alternative diagnosis to MS in these
patients.
PMID- 10192505
TI - Beta2 glycoprotein I containing immune-complexes in lupus patients: association
with thrombocytopenia and lipoprotein (a) levels.
AB - In this study we determined the prevalence and clinical associations of immune
complexes-containing beta-2-glycoprotein I (beta2GPI) in randomly selected SLE
patients. We studied 38 consecutive SLE patients attending the Rheumatology Unit.
Previous arterial or venous-thrombosis were documented by the appropriate
diagnostic test. Lipid profile including total cholesterol, LDL, VLDL, HDL and
Lp(a) levels were determined from the sera of the fasting patients. Antibodies to
cardiolipin, oxidized LDL and beta2GPI were detected employing ELISA. Beta2GPI
containing IgG immune-complexes were assayed by using a dot-blot assay. Fourteen
SLE patients (36.8%) were found to be positive for the presence of IgG anti
beta2GPI antibodies. Ten of the SLE patients (26.3%) were found to have high
levels of beta2GPI containing immune-complexes. There was a positive correlation
between beta2GPI-IC levels and the occurrence of thrombocytopenia in the patients
(P < 0.05). Furthermore, patients with SLE and venous thrombosis had higher
levels of beta2GPI-IC when compared with thrombosis-free patients or with healthy
controls (P < 0.05). Patients with higher Lp(a) levels (> 50 mg/dl) possessed
higher levels of beta2GPI-IC as compared with patients with lower Lp(a)
concentration (< 20 mg/dl) (P < 0.05). These results suggest that IC-containing
beta2GPI can help in defining a subpopulation of SLE patients with increased risk
of thrombocytopenia and further aid in resolving mechanisms of immune-mediated
tissue damage.
PMID- 10192506
TI - [Anti-beta2 glycoprotein I-beta2 glycoprotein I] immune complexes in patients
with antiphospholipid syndrome and other autoimmune diseases.
AB - Antiphospholipid syndrome (APS) is defined by the presence of aPL antibodies in
patients with thromboembolic phenomena. Some antiphospholipid (aPL) antibodies,
such as those directed against beta2-glycoprotein I (beta2GPI), are associated
with thromboembolism, possess Lupus Anticoagulant (LA) activity and recognize
their target antigen only when bound to specific surfaces or to phospholipids
(PL). To ascertain whether both free and antibody-bound beta2GPI circulate in
APS, we set up an ELISA to detect [IgG anti-beta2GPI-beta2GPI] immune complexes.
In this system, rabbit anti-human beta2GPI antibodies were adsorbed onto plastic
plates, incubated with patient plasma, and bound complexes were detected by means
of alkaline phosphatase-labeled goat anti-human IgG; each assay was stopped when
positive controls consisting of in vitro generated immune complexes reached an
Optical Density (OD) of 0.5 at 405 nm. Plasma from 16 patients with APS showed a
mean OD405 of 0.291 (range 0.115-0.558), not statistically different from the
mean obtained for 15 age- and sex-matched healthy volunteers (mean OD405 = 0.169,
range 0.066-0.264). Surprisingly, levels of immune complexes in 14 patients with
other autoimmune diseases and no circulating anti-beta2GPI antibodies were
statistically higher (mean OD405 = 0.552, range 0.204-0.991) than those of
healthy subjects and patients with APS. These data indicate that while
autoantibodies to beta2GPI are mainly unbound in plasma of patients with APS,
they are complexed with their antigen in patients with other autoimmune diseases,
possibly reflecting a higher binding affinity.
PMID- 10192507
TI - Antiphospholipid antibodies permeabilize and depolarize brain synaptoneurosomes.
AB - Antiphospholipid antibodies (aPL) are associated with neurological diseases such
as stroke, migraine, epilepsy and dementia and are thus associated with both
vascular and non-vascular neurological disease. We have therefore examined the
possibility that these antibodies interact directly with neuronal tissue by
studying the electrophysiological effects of aPL on a brain synaptosoneurosome
preparation. IgG from patients with high levels of aPL and neurological
involvement was purified by protein-G affinity chromatography as was control IgG
pooled from ten sera with low levels of aPL. Synaptoneurosomes were purified from
perfused rat brain stem. IgG from the patient with the highest level of aPL at a
concentration equivalent to 1:5 serum dilution caused significant depolarization
of the synaptoneurosomes as determined by accumulation of the lipophylic cation
[3H]-tetraphenylphosphonium. IgG from this patient as well as IgG from two
elderly patients with high levels of aPL were subsequently shown to permeabilize
the synaptosomes to labeled nicotinamide adenine dinucleotide (NAD) and pertussis
toxin-ADP-ribose transferase (PTX-A protein) as assayed by labeled ADP
ribosylation of G-proteins in the membranes. No such effects were seen with the
control IgG. aPL may thus have the potential to disrupt neuronal function by
direct action on nerve terminals. These results may explain some of the non
thromboembolic CNS manifestations of the antiphospholipid syndrome.
PMID- 10192508
TI - Anticardiolipin and anti-beta2glycoprotein-I antibodies in patients with systemic
lupus erythematosus: comparison between Colombians and Spaniards.
AB - We studied the prevalence, isotype distribution, and clinical significance of
anticardiolipin (aCL) and anti-beta2glycoprotein I (anti-beta2GPI) antibodies in
two populations of patients with systemic lupus erythematosus (SLE), 160
Colombians and 160 Spaniards. All sera were tested in our laboratory by enzyme
linked immunosorbent assay (ELISA) for IgG, IgM, and IgA aCL, as well as IgG and
IgM anti-beta2GPI. Positive results for at least 1 of the 3 aCL isotypes were
found in 40 Colombians (25%) and 55 Spaniards (34%). IgG aCL was the predominant
isotype in both populations. Positive results for at least 1 of the anti-beta2GPI
isotypes were found in 34 Colombians (21%) and 29 Spaniards (18%). IgG anti
beta2GPI was the dominant isotype in Colombians, while IgM was predominant in
Spaniards. Positivity for anti-beta2GPI in aCL-positive patients was present in
77% in the Colombian group and 50% in the Spaniard group. Among Colombians, IgG
aCL and anti-beta2GPI correlated with thrombosis, fetal loss, and
thrombocytopenia. Among Spaniards, IgG aCL and IgG anti-beta2GPI correlated with
thrombosis, fetal loss, and livedo reticularis. For detecting thrombosis and
fetal loss, aCL ELISA was more sensitive than anti-beta2GPI in Spaniards, and
anti-beta2GPI ELISA was more specific than aCL in both populations.
PMID- 10192510
TI - Chronic or recurrent headache in patients with systemic lupus erythematosus: a
case control study.
AB - Controversy exists concerning the prevalence of headache in systemic lupus
erythematosus (SLE) and its importance as a neuropsychiatric manifestation,
especially when it occurs independently of disease activity and with the typical
characteristics of primary chronic headache. Most reports to date have either
studied both types of headache, whether or not related to systemic lupus
erythematosus, or have not used adequate controls. This study determines the
prevalence and types of chronic primary headache in patients with systemic lupus
erythematosus in a case-control study which we performed in a tertiary care
hospital. We studied 71 consecutive patients with systemic lupus erythematosus
and 71 healthy unrelated subjects matched for age and sex from the same
geographical area. Clinical evaluation using a specific standard protocol for the
presence and characteristics of headache according to the operative
classification criteria of the International Headache Society. The overall
prevalence of headache, tension-type headache, and migraine was similar among
patients and controls [33 (46.5%), 17 (23.9%) and 16 (22.5%) vs 31 (43.7%), 17
(23.9%) and 13 (18.3%), respectively]. The mean age of onset of headache was
higher in the patients (28.7 +/- 14.3 vs 18.5 +/- 5.6 y; P = 0.001) and the
subjective response to analgesics was lower than in the controls [19 (63%) vs 28
(93.3%); P = 0.004]. There were no differences in the presence of precipitating
factors or family history of headache. There were no relevant clinical or
immunological differences among the patients regarding the presence or absence of
tension-type headache or migraine. Patients with systemic lupus erythematosus do
not differ from healthy controls for the presence and type of chronic or
recurrent headache.
PMID- 10192509
TI - Antibodies against lysophosphatidylcholine and oxidized LDL in patients with SLE.
AB - Lysophosphatidylcholine (LPC) is present in oxidized low density lipoprotein
(oxLDL), which is implicated in atherosclerosis. Antibodies to cardiolipin (aCL)
and oxLDL (aoxLDL) have been shown to crossreact. LPC is formed by hydrolysis of
phosphatidylcholine (PC) in LDL and cell membranes, induced by phospholipase A2
or by oxidation. We here demonstrate the presence of enhanced antibody levels to
LPC in 184 patients with SLE as compared to 85 healthy, age-matched controls. The
antibody reactivity to LPC was not specifically related to oxidation of the fatty
acid moiety in LPC, since LPC containing only the saturated fatty acid palmitic
acid showed equivalent antibody levels as LPC containing unsaturated fatty acids.
aPC were significantly lower as compared to aLPC, indicating that hydrolysis of
PC at the sn-2 position increases the antigenic potential of the molecule. Beta
glycoprotein 1 was a cofactor for aCL, but not for aoxLDL or aLPC, and the
antigenicity of these compounds is therefore not directly related to beta2GP1.
There was a close correlation between aoxLDL, aCL and aLPC and both LPC and oxLDL
competitively inhibited aCL-binding to CL. LPC, oxLDL and CL thus display a
common antigenic site, which could be formed by removal of a fatty acid at the sn
2 position, possibly due to the activity to phospholipase A2 and/or oxidation.
This study indicates the potential role of LDL-oxidation and phospholipase A2 in
SLE.
PMID- 10192511
TI - Systemic lupus erythematosus complicated by necrotizing fasciitis.
AB - A case of necrotizing fasciitis (NF) is described in a 46-year-old woman with
recent onset systemic lupus erythematosus (SLE). Deep-tissue infections are more
common in SLE patients on high-dose corticosteroids, but, to our knowledge, this
is the second case described in association with SLE. Although NF may initially
be difficult to diagnose, the presence of marked systemic symptoms out of
proportion to the local findings should suggest the correct diagnosis. NF
diagnostic criteria, treatment and prognosis are discussed.
PMID- 10192512
TI - Nodular regenerative hyperplasia of the liver and antiphospholipid antibodies:
report of two cases and review of the literature.
AB - Nodular regenerative hyperplasia of the liver (NRHL) is a rare disorder
characterized by diffuse micronodular transformation of the hepatic parenchyma
without fibrous septa between the nodules. This condition appears to be
associated in many occasions with systemic autoimmune diseases. We describe two
new patients with NRHL in whom antiphospholipid antibodies (aPL) were detected in
their sera and review the few similar cases reported previously. We also discuss
the possible relationship between aPL and NRHL and suggest that these antibodies
may play a role in the pathogenesis of some cases of NRHL, specially those with
an associated antiphospholipid syndrome.
PMID- 10192513
TI - Primary subcutaneous nocardial infection in a SLE patient.
AB - A patient with systemic lupus erythematosus (SLE) developed primary subcutaneous
nocardiosis during steroid and cyclophosphamide therapy for diffuse proliferative
glomerulonephritis. In spite of local process the patient manifested signs of
general deterioration mimicking SLE exacerbation. The diagnosis was made by
bacteriologic examination of the material obtained by CT guided aspiration.
Surgical drainage and systemic treatment with trimethoprim/sulphamethoxazole
(TMT/SMZ) 960 mg twice/d led to a clinical recovery and enabled the continuation
of the steroid and cytotoxic regimen.
PMID- 10192514
TI - Extraocular muscle proprioceptors and proprioception.
AB - Uncertainty of the roles of proprioception and efference copy in visual spatial
perception persists. Proprioception has won back some support recently mainly on
the evidence gained from physiological experiments in man, and rather than being
mutually exclusive, the two mechanisms have been presented as collaborating.
Another view supported by human and animal experiments states that current visual
spatial perception may be served by efference copy whereas proprioception is
responsible for temporal adaptations of the system. Certain characteristics of
visuomotor cells of the monkey cortex can be explained assuming an efference copy
input. Anatomical data from different sources are not easily reconciled.
Disagreement about the nerve pathway of muscle afferents weakens arguments based
on the results of open loop experiments involving nerve lesions in monkeys. The
assumed presence of Golgi tendon organs in human extraocular muscles is no longer
tenable and instead, palisade endings similar to those of cats and monkeys and
other, irregular nerve endings are described. But man differs in having a limited
and patchy distribution of neurotendonous endings and moreover, they may develop
only after infancy. The allocation of a sensory function to palisade endings in
myotendinous cylinders appears secure, at least in cats. Detailed examination of
muscle spindles in man reveals anomalies of structure sufficient to question
their capacity to provide useful proprioceptive information. One of the anomalies
is the atrophy of intrafusal muscle fibres, present in both infant and adult
muscles, and it is proposed that the redundant sensory endings, which do not
appear to degenerate, search for new targets and may account for the random
presence of tendon nerve endings. These observations place the role of
proprioception in human extraocular muscles in jeopardy; they are unsupportive of
the recent physiological studies and favour efference copy.
PMID- 10192515
TI - Stromal-epithelial interactions in the cornea.
AB - Stromal-epithelial interactions are key determinants of corneal function. Bi
directional communications occur in a highly coordinated manner between these
corneal tissues during normal development, homeostasis, and wound healing. The
best characterized stromal to epithelial interactions in the cornea are mediated
by the classical paracrine mediators hepatocyte growth factor (HGF) and
keratinocyte growth factor (KGF). HGF and KGF are produced by the keratocytes to
regulate proliferation, motility, differentiation, and possibly other functions,
of epithelial cells. Other cytokines produced by keratocytes may also contribute
to these interactions. Epithelial to stromal interactions are mediated by
cytokines, such as interleukin-1 (IL-1) and soluble Fas ligand, that are released
by corneal epithelial cells in response to injury. Other, yet to be identified,
cytokine systems may be released from the unwounded corneal epithelium to
regulate keratocyte viability and function. IL-1 appears to be a master regulator
of corneal wound healing that modulates functions such as matrix
metalloproteinase production, HGF and KGF production, and apoptosis of keratocyte
cells following injury. The Fas/Fas ligand system has been shown to contribute to
the immune privileged status of the cornea. However, this cytokine-receptor
system probably also modulates corneal cell apoptosis following infection by
viruses such as herpes simplex and wounding. Pharmacologic control of stromal
epithelial interactions appears to offer the potential to regulate corneal wound
healing and, possibly, treat corneal diseases in which these interactions have a
central role.
PMID- 10192516
TI - Corneal stromal wound healing in refractive surgery: the role of myofibroblasts.
AB - While laser and incisional refractive surgery offer the promise to correct visual
refractive errors permanently and predictably, variability and complications
continue to hinder wide-spread acceptance. To explain variations, recent studies
have focused on the role of corneal wound healing in modulating refractive
outcomes. As our understanding of the corneal response to refractive surgery
broadens, it has become apparent that the response of one cell, the corneal
stromal keratocyte, plays a pivotal role in defining the results of refractive
surgery. Studies reviewed herein demonstrate that injury-induced activation and
transformation of keratocytes to myofibroblasts control the deposition and
organization of extracellular matrix in corneal wounds. Myofibroblasts establish
an interconnected meshwork of cells and extracellular matrix that deposits new
matrix and contracts wounds using a novel and unexpected "shoe-string-like"
mechanism. Transformation of keratocytes to myofibroblasts is induced in culture
by transforming growth factor beta (TGFbeta) and blocked in vivo by antibodies to
TGFbeta. Overall, myofibroblast appearance in corneal wounds is associated with
wound contraction and regression following incisional keratotomy and the
development of "haze" or increased scattered light following laser
photorefractive keratectomy (PRK). By contrast, absence of myofibroblasts is
associated with continued widening of wound gape and progressive corneal
flattening after incisional procedures. Based on these studies, we have arrived
at the inescapable conclusion that a better understanding of the cellular and
molecular biology of this one cell is required if refractive surgery is ever to
achieve predictable and safe refractive results.
PMID- 10192517
TI - Immunoregulatory mechanisms of the eye.
AB - Immunity to protect the eye from invading pathogens is an absolute requirement
for the preservation of vision. However, immune responses carry their own threat
of tissue damage, due chiefly to the participation of non-specific inflammation.
Because of its delicate microanatomy, the visual axis is vulnerable to distortion
(and resulting blindness) from relatively trivial amounts of intraocular
inflammation. Therefore, regulation of expression of immunity in the eye is
critical to preservation of vision. Regulation of ocular immunity is one
expression of the general phenomenon of regional immunity in which local tissue
factors mold immune responses to local purposes. Ocular immune privilege is an
extreme example of regional immunity. Immune privilege is an active, rather than
a passive, process in which regulatory molecules and cells of the eye modulate
both the induction and the expression of immunity to eye-derived antigens. Immune
privilege is achieved primarily through unique features of the eye, ranging from
special microanatomic factors (blood:eye barrier, absence of lymphatic draining),
to soluble factors secreted by ocular cells into the ocular microenvironment, to
regulatory molecules constitutively expressed on the surfaces of ocular cells. In
general, the most important consequence of regulation of ocular immune responses
is the virtual elimination of immunogenic inflammation from the eye. While this
enables the eye to receive immune protection without the threat of blinding
inflammation, it also renders the eye vulnerable to those pathogens whose
elimination requires the participation of inflammatory molecules and cells.
PMID- 10192518
TI - The prevalence of age-related maculopathy by geographic region and ethnicity.
AB - The prevalence of age-related maculopathy (ARM) varies considerably in different
locations and racial/ethnic groups around the world. At present there are
insufficient data to determine whether it is likely that these differences in
prevalence, especially for the early forms of ARM are due to variations in
genetic and environmental factors or due to variations in age of the cohorts and
methods used to ascertain and define ARM. In three population-based studies of
whites living in Beaver Dam, Wisconsin, Blue Mountains, Australia, and Rotterdam,
The Netherlands, in which similar methods of ascertainment and classification
were used to detect and define ARM, late ARM was present in 1.2%, 1.4%, and 1.2%
of the population less than 86 years of age, respectively. While data from
clinical studies suggest that late ARM associated with choroidal
neovascularization is rare in blacks compared with whites, some epidemiological
studies suggest that late ARM may be similar in blacks and whites. There are
still too few data from various ethnic/racial groups around the world and too few
population-based data in older Hispanic and Asian populations to make meaningful
comparisons. There is a need for further research into the distribution of ARM
and its possible causes using similar methodologies to ascertain and define the
disease. Further insights will be gained when genotypes associated with ARM are
discovered.
PMID- 10192519
TI - Theoretical and experimental basis for the inhibition of cataract.
AB - Aggregation of the lens proteins to form high molecular weight clusters is a
major contributing factor in age-onset nuclear cataract [Benedek, G. B. (1971)
Theory of transparency of the eye. Appl. Optics, 10, 459-473]. This aggregation
occurs continually throughout life and contributes to an exponential increase, as
a function of age, in the intensity of the light backscattered out of the lens.
The time constant deltaT for this exponential increase in human populations is a
valuable index, helpful for conducting clinical trials. In-vitro studies have
identified reagents capable of inhibiting high molecular weight aggregate
formation, as well as the non-covalent interprotein interactions responsible for
phase separation. These reagents are also found experimentally to be effective
cataract inhibitors in animal model systems in vivo. We believe that the stage is
now set for human clinical trials of putative cataract inhibitors. We present
rough quantitative estimates of the trial parameters needed to assure an
unambiguous determination of efficacy in a trial population. Such a trial simply
requires a measurement of the time constant deltaT in the treated population
relative to the untreated population. A successful outcome of the trial is
indicated if deltaT increases by 20% over that found for the untreated
population. Our estimates suggest efficacy could be determined in a two year
trial involving about 300 subjects in the treated group.
PMID- 10192520
TI - Differential gene expression in the human ciliary epithelium.
AB - The generation of expression and subtractive libraries from the ocular ciliary
body and cultured ciliary epithelial cells has been instrumental in the cloning,
identification and characterization of many genes which, overall reflect a
representative profile of transcripts expressed in ciliary nonpigmented, ciliary
pigmented and ciliary muscle cells. The cell-specific expression of some of these
genes (i.e. a neurotrophic factor, a gene associated with juvenile open glaucoma,
and a visual component) reveal a degree of cell differentiation with a diversity
of functions and properties higher than previously thought. The protection from
light-induced oxidative reactions, free radicals and detoxification, may be
partially attributed to the high level of expression in the ciliary epithelium of
antioxidative enzymes (i.e., glutathione S-transferase, glutathione peroxidases,
selenoprotein-P). The expression of genes encoding plasma proteins (i.e.,
complement component C4, alpha2-macroglobulin, apolipoprotein D) is in contrast
with the view that plasma proteins in aqueous humor are synthesized outside the
eye (i.e., liver). The identification of neuropeptide-processing enzymes (i.e.,
prohormone convertases, carboxypeptidase E, peptidyl-glycine-alpha-amidating
monoxigenase), neuropeptides (i.e., secretogranin II, neurotensin) and regulatory
peptides (i.e., atrial natriuretic peptide and angiotensinogen) with hypertensive
and hypotensive activities provide the molecular basis to support the view that
the ciliary epithelium is a neuroepithelium with neuroendocrine functions. We
propose a working model to demonstrate that aqueous humor and intraocular
pressure are under neuroendocrine control through regulatory peptides synthesized
and released by the ciliary epithelium and targeting the peptide producing cells
at the inflow system by an autocrine mechanism and/or cells at the outflow system
(i.e., trabecular meshwork cells) by a paracrine mechanism. Finally, we
hypothesize that these mechanisms could be entrained in the light-dark cycle
following the circadian rhythm of aqueous humor and intraocular pressure.
PMID- 10192521
TI - Meningeal cells stimulate and direct the migration of cerebellar external granule
cells in vitro.
AB - The external granular layer is a secondary proliferative zone that arises from
the caudolateral margin of the cerebellar ventricular zone and then spreads
beneath the pial surface, eventually covering the entire cerebellar anlage. Here,
both a part of the Bergmann glia and granule cells are generated. Selective
destruction of the leptomeningeal cell layer during development in vivo disrupts
the subpial extension of the external granular layer and the laminar deposition
of its descendant cells. The mechanisms by which meningeal fibroblasts exert
their controlling influence on cortical development have remained unclear but
could involve diffusible factors and/or interactions mediated by direct cellular
contacts. In order to test these assumptions, we have co-cultivated cerebellar
slice explants with meningeal cells with and without interposition of a
microfilter barrier. In this setup, meningeal cells by a diffusible factor
stimulated the emigration of immature neurons exclusively from the external
granular layer. This effect could also be elicited by fibroblasts from other
tissues but not by nonfibroblastic cells such as, e.g., astroglia. In the Boyden
chamber assay, the migration of undifferentiated neurons isolated from the
external granular layer was chemotactically oriented towards the source of
meningeal cell conditioned media. In comparison, neurons from the internal
granular layer did not respond to this stimulus. The attraction of immature
neurons towards the pial surface could (1) represent a mechanism for the
establishment of (subpial) secondary proliferative zones and (2) hypothetically
also play a role in the outward-directed migration of postmitotic cells, e.g., in
the isocortical anlage.
PMID- 10192522
TI - Altered subcellular localization patterns of ferritin and beta-actin mRNAs in
muscle cultures, resulting from incomplete penetration of digoxigenin-labelled
riboprobes.
AB - Protocols for in situ hybridization (ISH) of cultured cells often include storage
in alcohol at -20 degrees C between fixation of the cultures and the ISH
procedure. In experiments aimed at localizing ferritin mRNA in C2 muscle cultures
by ISH with digoxigenin-labelled riboprobes, we have noticed that omission of the
ethanol storage dramatically changed the pattern of mRNA localization. In
cultures stored in 50%, 70%, or 90% ethanol for at least 15 min, ferritin signal
was stronger on myotubes than myoblasts but was uniformly distributed over both.
In untreated cultures, the signal was patchy, concentrated on the extremities of
the elongated myoblasts and very sparse in myotubes. Similar results were
obtained with a probe to beta-actin used as a control, except that signal was
higher in myoblasts in all conditions. When the probes were reduced in size to
approximately 100 bases from 561 for ferritin and 1150 for actin, the pattern
became uniform, regardless of prehybridization treatment. The patchy pattern
disappeared when cells were treated with RNase A following hybridization,
suggesting that it is non-specific, despite its absence in cultures hybridized
with a sense probe. We conclude that incomplete access of RNA probes can result
not only in a reduced ISH signal but also in artefactual patterns of mRNA
localization.
PMID- 10192523
TI - The first-order giant neurons of the giant fiber system in the squid:
electrophysiological and ultrastructural observations.
AB - The giant fiber system controlling mantle contraction used for jet propulsion in
squid consists of two sets of three giant neurons organized in tandem. The somata
of the 1st- and 2nd-order giant cells are located in the brain, while the
perikarya of the 3rd-order giant cells are encountered in the stellate ganglia of
the mantle. The somata and dendrites of one fused pair of 1st-order giant cells
are thought to receive synaptic input from the eye, statocyst, skin
proprioceptors, and supraesophageal lobes. To define the cellular properties for
integration of such an extensive synaptic load, especially given its diversity,
intracellular recordings and electron microscopic observations were performed on
1st-order giant cells in an isolated head preparation. Spontaneous bursts of
action potentials and spikes evoked by extracellular stimulation of the brachial
lobe were sensitive to the Na+ channel blocker TTX. Action potentials were also
abolished by recording with microelectrodes containing the membrane impermeant,
use dependent Na+ channel blocker QX-314. The small action potential amplitude
and the abundant synaptic input imply that the spike initiation zone is remotely
located from the recording site. The high spontaneous activity in the isolated
head preparation, as well as the presence of synaptic junctions resembling
inhibitory synapses, suggest; that afferent synapses on 1st-order giant neurons
might represent the inhibitory control of the giant fiber system. The
characterization of the electroresponsive properties of the 1st-order giant
neurons will provide a description of the single cell integrative properties that
trigger the rapid jet propulsion necessary for escape behavior in squid.
PMID- 10192524
TI - Ultrastructural observations of astrocyte end-feet in the rat central nervous
system.
AB - Astrocytic end-feet in the rat CNS were studied by thin section electron
microscopy. Astrocyte processes that enclose neuronal elements extended to blood
vessels and the pia mater, where the processes expanded to form end-feet or glial
limiting membranes. At the end-feet, cell junctions such as gap junctions and
desmosome-like junctions were formed between the astrocyte processes. The end
foot plasma membrane facing the basal lamina was undercoated with electron-dense,
layered materials, with an internal substructure of filamentous networks, with
which bundles of glial filaments (GFs) appeared to be closely associated via fine
filamentous structures, often showing a hemi-desmosome-like appearance. In
specimens treated with Triton X-100, the internal substructure of the undercoat
was better visualized and the association with GFs was well preserved. At the end
feet, some unique tubular structures were found in spatial relationship to the
plasmalemmal undercoat. Plectin visualized by immunofluorescence was localized to
astrocytes and their processes, especially at the end-feet facing the pia mater.
Immunoelectron microscopy located plectin on fine filamentous structures lying
between GFs and the plasmalemmal undercoat. These observations suggest that
plasmalemmal undercoats at the astrocyte end feet may serve as attachment sites
of GFs to the plasma membrane and that plectin may be involved in such
attachment.
PMID- 10192525
TI - Cellular reactions to axotomy in rat superior cervical ganglia includes apoptotic
cell death.
AB - The cellular response to axonal injury in the superior cervical ganglion was
examined by immunofluorescence at intervals from 6 h to 14 days after transection
of the internal and external carotid nerves. GAP-43-immunoreactivity (IR)
appeared in some neurons in the ganglia 1 day after axotomy, while neurons in
control ganglia were GAP-43 negative. In 3 days axotomized ganglia GAP-43-IR
structures were increased in number and intensity in nerve fiber bundles, while
GAP-43-positive perikarya were restricted to the middle and caudal parts of the
ganglia and showed an intensity that was stronger than at 1 day after axotomy.
These GAP-43-positive neurons were also galanin positive. In the cranial part of
the ganglia, S100-IR in satellite cells was weak at 18 h after axotomy.
Peripheral to this area, S100-IR was stronger and co-localized with HSP-72-IR,
preferentially located in satellite cells. HSP-72-IR was, however, occasionally
observed also in principal neurons at 1 and 3 days after axotomy. In eosin
stained sections, neurons and satellite cells in the cranial part of 1 day
axotomized ganglia were reduced in number, and a further loss was noted at 3
days. At 12 h some satellite cells in the cranial part of the ganglia were
labelled by the in situ DNA 3'-end labelling method, indicating apoptosis, and at
18 h many cells were labelled. Some neuronal perikarya were also labelled in this
region. Labelling was not observed at 1 day or later after axotomy, nor in
control ganglia. The results may imply that not only neurons but also satellite
cells react to neuronal axonal injury with apoptosis. Neurons in the middle and
caudal part of the ganglia survived and showed increased content of GAP-43 and
galanin, possibly a sign of regeneration/neuronal plasticity.
PMID- 10192526
TI - Cytochalasin D disrupts the restricted localization of N-CAM, but not of L1, at
sites of Schwann cell-neurite and Schwann cell-Schwann cell contact in culture.
AB - The neural recognition molecules L1 and N-CAM have been shown to be
preferentially localized at sites of Schwann cell-to-neurite and Schwann cell-to
Schwann cell contact in vitro. In the present study, we investigated the
mechanisms underlying the restricted expression of these molecules at the Schwann
cell surface, focusing on the possible role of actin filaments. Co-cultures
consisting of Schwann cells from newborn mice and explants of dorsal root ganglia
from chicken embryos were maintained in the absence or presence of cytochalasin
D, an agent disrupting actin filaments. Immunoelectron microscopy with mouse
specific antibodies was carried out to quantify the restricted localization of L1
and N-CAM at the Schwann cell surface in contact with neurites. After 2 days of
co-culturing in the absence of cytochalasin D, approximately 65% of the cell cell
contacts showed a restricted immunoreactivity for L1 and N-CAM. The accumulation
of L1 at contact sites was unchanged in cytochalasin D-treated co-cultures, while
the agent strongly reduced the restricted localization of N-CAM to 20% of all
cell-cell contacts. The disruption of N-CAM accumulation appeared to be rapid and
occurred within 5 h of cytochalasin D treatment. These results indicate that the
restricted localization of N-CAM, but not of L1, is sensitive to cytochalasin D
treatment, suggesting a dependence on the integrity of the actin network. Thus,
different mechanisms may regulate the subcellular distribution of cell adhesion
molecules in Schwann cells.
PMID- 10192527
TI - Serotonergic innervation of the foot of the pond snail Lymnaea stagnalis (L.).
AB - The aminergic innervation of the foot of Lymnaea stagnalis was investigated using
electron microscopy, immunocytochemistry, and HPLC. The foot was found to contain
large amounts of serotonin and dopamine, though at lower concentrations than are
found in nervous tissue. Serotonin containing tissue was concentrated in the
ventral surface of the foot, under ciliated areas of the epidermis where it
occurred in varicosities, with fine tracts joining these varicosities.
Varicosities also occurred in deeper tissues, probably adjacent to mucus cells.
Positive fluorescence for serotonin in axons was found in nerves innervating the
foot, but few neuronal cell bodies containing serotonin were detected, indicating
that most of the innervation was coming from the central ganglia. Axon
varicosities were found using TEM on ciliated cells, mucus cells, and muscle
cells as well as interaxonal junctions (possibly non-synaptic) within nerves. The
neuronal varicosities contacting the ciliated cells and mucus cells contained
mostly dense-cored vesicles of between 60 and 100 nm in diameter. Smaller, lucent
vesicles also occurred in these terminals. The origin and significance of this
innervation is discussed. It is suggested that both serotonin and dopamine may
play a large role in controlling ciliary gliding by the foot.
PMID- 10192528
TI - Thrombospondin 1 is expressed by mesenchymal cells in mouse post-natal skin and
hair follicle development.
AB - Thrombospondin 1 is an extracellular matrix glycoprotein with multiple functions.
In the skin, it has been immunolocalized to basement membrane, and its expression
increases during embryogenesis and wound healing. Its normal cellular source in
the skin is not known, except during wound healing, where macrophages and
keratinocytes seem to be the primary source. We have analysed the expression of
thrombospondin 1 mRNA in normal mouse skin at different ages by in situ
hybridization. It was found that the mRNA is expressed by dermal mesenchymal
cells and mature fibroblasts and developmentally regulated during post-natal skin
growth and morphogenesis. In adult mouse skin, expression of the thrombospondin
is restricted to the mesenchymal cells of hair follicle papilla. These results
suggest that the regulation of thrombospondin 1 transcription in mesenchymal
cells can play an important role in post-natal skin development. Its mRNA
expression is a characteristic of adult dermal papilla cells with a potential
role in hair development.
PMID- 10192529
TI - Ovariectomy causes cell proliferation and matrix synthesis in the growth plate
cartilage of the adult rat.
AB - The in vivo effects of ovariectomy in rats have been studied on cell
proliferation and matrix synthesis in the growth plate cartilage by assessing
immunohistochemically the levels of proliferating cell nuclear antigen and
chondroitin sulphate proteoglycan(s). The serum levels of insulin-like growth
factor-I and growth hormone were also measured by radioimmunoassay procedures. At
5 weeks after ovariectomy, the serum levels of the growth factor were
significantly higher than those in sham-operated rats. In contrast, the level of
growth hormone was lower. The nuclear staining of proliferating cell nuclear
antigen was generally seen in the zone of proliferative chondrocytes from both
groups of rats. Whereas almost all chondrocytes in the proliferative zone of
ovariectomized rats expressed proliferating cell nuclear antigen
immunoreactivity, fewer did so in that of the sham rats. Quantitative image
analysis by ACAS 570 laser cytometry demonstrated that the nuclear antigen
positive sites in ovariectomized rats had significantly higher integrated values
(staining intensity), areas and perimeters than those in sham rats. In addition,
the number of chondroitin sulphate proteoglycan-immunoreactive cells in the
proliferative chondrocytes was also higher in ovariectomized rats than in sham
ones. These results suggest that ovariectomy significantly stimulates the cell
proliferation and matrix synthesis in the growth plate cartilage, probably
through the higher serum level of insulin-like growth factor-I.
PMID- 10192530
TI - Classification of bovine muscle fibres by different histochemical techniques.
AB - The classification of bovine muscle fibres is of particular interest for the food
industry because meat tenderness depends in part on the proportion of the
different types of fibres. It is, therefore, important to define reliable methods
for classifying fibre types. There are several classification systems. One is
based on contractile type alone, as revealed by myofibrillar ATPase activity or
with antibodies against myosin heavy chain. Others take both contractile and
metabolic types into account. In this study, the classifications of fibres
obtained by these three systems were compared on the semitendinosus and
longissimus thoracis muscles of 35 Charolais bulls. Only the use of antibodies
allowed the identification of a proportion of hybrid fibres containing two
isoforms of fast myosin heavy chain (2a and 2b). In addition, the combination of
metabolic types showed that the metabolism of these hybrid fibres differed
according to the muscle.
PMID- 10192531
TI - Localization of carbonic anhydrase in the sperm-storing regions of the turkey and
quail oviduct.
AB - The localization of carbonic anhydrase in the sperm storage regions of turkey and
quail was investigated using a histochemical method showing the activity of all
the isozymes present. Intense carbonic anhydrase activity was found in the turkey
sperm storage tubules and infundibular storage glands, whereas no activity could
be detected in the quail at these sites. Both species did, however, show strong
membrane-bound and cytoplasmic activity in the non-ciliated cells of the utero
vaginal surface epithelium and scattered cells of the vaginal epithelium. The
enzyme catalyses the reaction CO2 + H2O <--> H+ + HCO3-, and the presence of
carbonic anhydrase in these regions makes rapid changes in pH possible. It is
suggested that increasing pH and/or the addition of bicarbonate stimulates sperm
motility needed during transfer of the oviducal lumen. A lowering of the pH would
keep the sperm quiescent during storage. The duration of sperm storage is
considerably longer in the turkey than in the quail. The high quantity of
carbonic anhydrase in the turkey sperm storage tubules may, thus, play a role in
the duration of sperm storage.
PMID- 10192532
TI - Immunohistochemical localization of carbonic anhydrase isoenzymes II and III in
quail kidney.
AB - The immunohistochemical localization of carbonic anhydrase isoenzymes has never
been investigated in avian renal tissue previously. Enzyme activity has largely
been documented by histochemical and physiological reports. In this
investigation, specific antisera were used to study the distribution of the
cytosolic carbonic anhydrase II and III isoenzymes in the quail kidney.
Comparison between the present findings and the corresponding histochemical
patterns, previously obtained in the same species by a cobalt phosphate
precipitation method, resulted in the bulk of renal carbonic anhydrase activity
being attributed to the carbonic anhydrase II isoenzyme. Conversely, moderate
carbonic anhydrase III immunostaining appeared to be confined to the smooth
muscle cells of ureteral and arteriolar walls. Indirect evidence of the
occurrence, in the quail kidney, of a membrane-associated carbonic anhydrase
form, antigenically distinct from the II and III isoforms, was inferred.
PMID- 10192533
TI - Detection and characterization, using fluoresceincadaverine, of amine acceptor
protein substrates accessible to active transglutaminase expressed by rabbit
articular chondrocytes.
AB - The purpose of this study was to investigate the implication of transglutaminases
in the biology of articular chondrocytes. Transglutaminase activity measurements
performed on cell lysates showed that a transglutaminase was present in
chondrocytes in primary culture and that it was strongly activated by limited
proteolysis. In chondrocytes dedifferentiated by subculture or retinoic acid
treatment, this transglutaminase appeared to be downregulated, while type II
transglutaminase expression was induced. However, protein levels, mRNA steady
state levels or transglutaminase activity in whole-cell lysates do not
necessarily reflect the activity present in living cells, as it is strongly
regulated. Therefore, Fluoresceincadaverine, a fluorescent polyamine, was used
for detecting amine acceptor protein substrates accessible to active
transglutaminase in living cells. After incubation of chondrocytes with
Fluoresceincadaverine, dedifferentiated cells exhibited an extracellular
labelling, while chondrocytes in primary culture did not, unless thrombin was
added to the culture medium. In contrast, Fluoresceincadaverine labelling was not
detected in the cytosol, although the transglutaminases were also partly
cytosolic. By confocal microscopy and Western blot analysis of labelled cells in
culture, fibronectin was shown to be the main substrate for both
transglutaminases. The transglutaminases present in articular chondrocytes may,
therefore, contribute to the organization and the stabilization of their
extracellular matrix.
PMID- 10192534
TI - Differential localization of heat shock proteins 90, 70, 60 and 27 in human
decidua and placenta during pregnancy.
AB - Little is known about the localization of heat shock proteins (HSPs) in the
decidua and placenta during the course of normal pregnancy. In this study, we
have examined the localization of the HSPs in decidual and placental tissues
obtained from women during the first, second and third trimesters of pregnancy
(five in each trimester) by immunohistochemistry using highly specific antisera.
HSPs 90, 70, 60 and 27 were detected in decidual stromal cells during each
trimester. The intensity of staining did not change during gestation for HSPs 60
and 27, whereas it decreased with advancing gestation for HSPs 90 and 70. HSPs 90
and 60 were localized primarily in the nucleus, whereas HSP 70 was present
equally in the nucleus and the cytoplasm; HSP 27 was primarily in the cytoplasm.
In the placenta, HSPs 90, 70 and 60 were localized in cytotrophoblast,
syncytiotrophoblast, intermediate trophoblast, Hofbauer and endothelial cells.
HSPs 90 and 60 were localized primarily in the nucleus, while HSP 70 was in the
nucleus and the cytoplasm. In the placenta, HSP 27 was detected only in the
intermediate trophoblast and syncytiotrophoblast cells and only in the first two
trimesters. These results indicate that there are striking differences in the
subcellular localization of HSPs in the decidua and the placenta during normal
pregnancy.
PMID- 10192535
TI - The proteoglycans and glycosaminoglycan chains of rabbit synovium.
AB - The synovial lining of joint capsules is important because it controls the flow
of fluid into and out of the joint cavity. Physiological studies have shown that
the glycosaminoglycans, particularly hyaluronan, have an important role in the
control of fluid flow. The distribution of the glycosaminoglycans and
proteoglycans in the synovium and subsynovium of rabbits (approximately 12 weeks
old) was, therefore, determined immunohistochemically. Hyaluronan, chondroitin-4-
and chondroitin-6-sulphates and keratan sulphate are present in the synovium and
subsynovium; chondroitin-4-sulphate is at higher concentrations than chondroitin
6-sulphate. The core proteins of the chondroitin sulphate proteoglycans, biglycan
and decorin, and of the keratan sulphate proteoglycan, fibromodulin, are also
present. To date, fibromodulin has not been located in other synovial linings,
and its presence corroborates that of keratan sulphate.
PMID- 10192536
TI - Regional difference in the distribution of vasoactive intestinal polypeptide
immunoreactive nerve fibres along the uterus and between myometrial muscle layers
in the rat.
AB - To investigate a possible regional variation of the vasoactive intestinal
polypeptide innervation in the uterus of the cyclic rat, the distribution of
vasoactive intestinal polypeptide-containing nerve fibres from the cervix to the
oviduct end of the uterine horns was studied using immunohistochemistry.
Immunoreactive nerve fibres were most concentrated in the cervix, where they
formed a dense plexus in association with the musculature and surrounding blood
vessels. In the uterus, a clear regional distribution of the vasoactive
intestinal polypeptide innervation was observed. Numerous vascular and non
vascular immunoreactive nerve fibres were present in the lower part of the
uterine horns, whereas they were sparse in the median region and absent at the
oviduct end. Moreover, non-vascular peptide innervation was mostly concentrated
in the circular layer of the myometrium and also occurred in the endometrium.
Only a very few immunoreactive nerve fibres were present in the longitudinal
muscle layer. No change in the peptide innervation pattern was observed during
the different stages of the sexual cycle. The marked regional distribution of the
peptide innervation in the rat uterus suggests that the regulatory effects of the
peptide occur mainly in the lower part of the organ and principally affect the
circular muscle layer in the myometrium.
PMID- 10192537
TI - Immunohistochemical localization of constitutive and inducible cyclo-oxygenases
in rat uterus during the oestrous cycle and pregnancy.
AB - The uterus is a rich source of eicosanoids synthesized from arachidonic acid
metabolism through the cyclo-oxygenase pathway. Two isoforms of cyclo-oxygenase,
constitutive (COX-I) and inducible (COX-II) enzyme, have been reported. In the
present study, we have immunohistochemically mapped the distribution of both COX
I and COX-II during various physiological states of the rat uterus. Uterine
tissue was collected from female rats (a) during different stages of the oestrous
cycle, (b) on days 1, 4, 8 and 18 of gestation, (c) after spontaneous delivery
and (d) post partum, and fixed in Bouin's fixative. After paraffin wax embedding,
5-microm-thick sections were immunohistochemically stained by the ABC technique.
Observation of the stained sections under the light microscope revealed that, in
non-pregnant rat uterus, both COX-I and COX-II were abundantly expressed in the
endometrium, with minimal staining observed in the myometrium. Staining was more
prominent in epithelial cells than in stromal cells. The intensity of staining in
epithelial cells was highest at pro-oestrus and oestrus and lowest at dioestrus.
In pregnant rats, although the expression of both COX-I and COX-II was localized
primarily to the endometrium with very little staining in the myometrium on day 1
of gestation, both of these enzymes were also apparent in myometrial cells by day
4 of gestation. The staining intensity of endometrial and myometrial cells
increased further with the progression of gestation, being maximal at the time of
spontaneous delivery. During the post-partum period, however, the staining
intensity for both of the enzymes in endometrium and myometrium was decreased.
Thus, our studies show that the expression of cyclo-oxygenases in various uterine
cells vary with the oestrous cycle and with pregnancy. Furthermore, prominent
increases in the expression of cyclo-oxygenases in the myometrium during
pregnancy and parturition imply that the cyclo-oxygenase system in the myometrium
may play a major role in modulating uterine contractility during pregnancy and
labour.
PMID- 10192538
TI - Transforming growth factor beta1 involvement in the conversion of fibroblasts to
smooth muscle cells in the rabbit bladder serosa.
AB - In an attempt to identify the growth factors or cytokines involved in the serosal
thickening that occurs in rabbit bladder subjected to partial outflow
obstruction, the following growth factors--transforming growth factor beta1,
platelet-derived growth factor, epidermal growth factor, granulocyte colony
stimulating factor and granulocyte-monocyte colony-stimulating factor--were
delivered separately onto the serosal surface of the intact bladder via osmotic
minipumps. The proliferative/differentiative cellular response of the rabbit
bladder wall was evaluated by bromodeoxyuridine incorporation and
immunofluorescence staining with a panel of monoclonal antibodies to cytoskeletal
proteins (desmin, vimentin, keratins 8 and 18 and non-muscle myosin) and to
smooth muscle (alpha-actin, myosin and SM22) proteins. Administration of the
transforming growth factor, but not of the other growth factors/cytokines, was
effective in inducing serosal thickening. Accumulating cells in this tissue were
identified as myofibroblasts, i.e. cells showing a mixed fibroblast-smooth muscle
cell differentiation profile. The phenotypic pattern of myofibroblasts changed in
a time-dependent manner: 21 days after the growth factor delivery, small bundles
of smooth muscle cells were found admixed with myofibroblasts, as occurs in the
obstructed bladder. These 'ectopic' muscle structures displayed a variable
proliferating activity and expressed an immature smooth muscle cell phenotype.
The complete cellular conversion to smooth muscle cells was not achieved if
transforming growth factor beta1 was delivered to fibroblasts of subcutaneous
tissue. These findings suggest a tissue-specific role for this growth factor in
the cellular conversion from myofibroblast to smooth muscle cells.
PMID- 10192539
TI - Is acid phosphatase activity present in bone matrix at sites of endochondral
ossification in rabbit fracture callus?
AB - It has been suggested that acid phosphatase activity is present in newly formed
bone matrix at sites of endochondral ossification in rabbit fracture calluses.
Because acid phosphatases are usually found intracellularly, it was decided to
test this possibility more rigorously. Tissue from 10- and 14-day healing rabbit
fractures was subjected to a series of critical tests for acid phosphatases with
a pH optimum of 5.0. Fluoride, tartrate and molybdate were used as potential
inhibitors of acid phosphatase activity. The effects of several counterstaining
protocols were also investigated. A fluoride- and tartrate-resistant acid
phosphatase is located in osteoclasts and mononuclear phagocytes. Diffuse
staining of the bone matrix is seen, but it is dependent upon the length of
incubation in the substrate medium and the distance from the acid phosphatase
reacting cells. It is concluded that the coloration of the bone matrix is
probably caused by diffusion of the dye and reaction product and is, therefore,
artifactual.
PMID- 10192540
TI - Immunohistochemical distribution of connexin 43 in the cartilage of rats and
mice.
AB - Using fluorescence immunohistochemistry, the distribution of connexin 43 was
examined in hyaline cartilage and in the perichondrium of mouse and rat knee
joints. In addition, rat chondrocytes were shown to be coupled in dye transfer
studies with Lucifer Yellow. Connexin 43 was detected between chondrocytes in the
outer layer of knee joint cartilage, between chondrocytes of the growth plate and
between fibrocartilage-like cells at tendon and ligament insertions and in the
tendons and ligaments proper. However, in the hyaline cartilage of the hind limbs
of mature rats, the degree of connexin 43 immunoreactivity was diminished. These
data suggest a possible involvement of connexins in cartilage development.
PMID- 10192541
TI - Immunohistochemical localization of haemoglobin binding sites in the distal
tubule of the rat kidney.
AB - Although it is well established that haemoglobin can be taken up by kidney
tubular epithelium, the exact mechanism of the process has not been elucidated so
far. We have undertaken a study to determine whether any specific binding sites
for haemoglobin are present on the membranes of renal tubular cells. Paraffin
sections of rat kidney cortex were incubated with haemoglobin, and the bound
molecules were detected by means of a combined avidin-peroxidase and ImmunoMax
method. Haemoglobin binding sites were observed in the apical membrane of distal
tubules. Binding occurred for both rat haemoglobin and swine and human
haemoglobins, and the proteins could compete with each other. Competition
experiments with other proteins showed that the binding is specific for
haemoglobin and that the net charge of the protein is not critical for the
interaction. We failed to detect the binding sites in proximal tubules, where
most of the filtered proteins are reabsorbed. The role of the binding sites in
the distal nephron is unclear. Our findings may be essential for the further
understanding of the pathomechanism of haemoglobin-induced acute renal failure.
PMID- 10192542
TI - Production of monoclonal antibody against histamine and its application to
immunohistochemical study in the stomach.
AB - A monoclonal antibody against histamine has been produced. A histamine
haemocyanin conjugate prepared using 1-ethyl-3-(3-dimethylaminopropyl)
carbodiimide as a coupling agent was used for immunizing mice. Immunized mice
were sacrificed to prepare monoclonal antibody using a hybridoma technique. On
immunospot assay, the hybridoma culture supernatant containing a monoclonal
antibody was capable of detecting 50 pmol of histamine. Using this antibody, we
examined the cellular localization of histamine-like immunoreactivity in the
stomach of normal or alpha-fluoromethylhistidine-treated rats and mice.
Immunoreactive cells were abundant in the gastric mucosal layer. These positive
cells were often located in the basal half of the fundic gland but were rare in
the pyloric gland. The cells, small or medium in size, spindle or cone in shape,
were intermingled with immunonegative epithelial cells. In the cytoplasm of the
positive cells, granular reaction products were densely deposited. In addition, a
few positive cells, identified as mast cells by Toluidine Blue staining, were
distributed mainly in the submucosal and muscular layer. The antibody preabsorbed
with 10 mM histamine gave no positive immunostaining. For pharmacological study,
some rats were injected six times with c-fluoromethylhistidine every 8 h. In
these rats, positive cells except mast cells were no longer detected. In
conclusion, the monoclonal antibody produced appears to be highly specific for
histamine. Its application in immunohistochemistry should provide a powerful tool
for analysing the roles of histamine in enterochromaffin-like or mast cells in
the stomach.
PMID- 10192543
TI - Hints of a functional connection between the neuropeptidergic innervation of
arteriovenous anastomoses and the appearance of epithelioid cells in the rabbit
ear.
AB - Peripheral blood flow can be regulated by specialized vessel segments, the
arteriovenous anastomoses. Their wall consists of a relatively thick layer of
smooth muscle cells and so-called epithelioid cells. The epithelioid cell is a
specialized myogenic cell phenotype expressing nitric oxide synthase. We studied
the innervation of the different segments of arteriovenous anastomoses in the
rabbit ear using antisera against neuropeptide Y, tyrosine hydroxylase,
calcitonin gene-related peptide and substance P, as well as neuron-specific
enolase, calbindin D and neurotubulin. The participation was especially examined
of neuropeptidergic innervation and a possible morphological connection to the
occurrence of epithelioid cells and a paracrine function. The NADPH diaphorase
reaction and alpha-smooth muscle actin immunoelectron microscopy served to
distinguish epithelioid cells from smooth muscle cells. Using conventional
fluorescence microscopy and confocal laser scanning microscopy, we found the most
dense innervation pattern of pan-neuronal markers (neurotubulin, neuron-specific
enolase), tyrosine hydroxylase-immunoreactive nerve fibres and neuropeptidergic
nerve fibres (neuropeptide Y, calcitonin gene-related peptide, substance P)
around the intermediate segment in arteriovenous anastomoses, whereas the venous
segment was barely marked. Single nerve fibres penetrated into the medial layer
and reached the epithelioid cells. Using immunoelectron microscopy, we found
intercellular contacts between epithelioid cells, but not the gap junction
protein connexin 43. Here, we report for the first time a correlation of the
innervation pattern with epithelioid cell type in arteriovenous anastomoses. Our
findings suggest that epithelioid cells of the arteriovenous anastomoses are
controlled by a dense network of neuropeptidergic nerve fibres in functional
connection to their paracrine role as a nitric oxide producer.
PMID- 10192544
TI - Characterization of glycoconjugates of guinea pig seminal vesicle by lectin
histochemistry.
AB - In the present study, the expression of glycoconjugates in the guinea pig seminal
vesicle was localized and partially characterized by lectin histochemistry using
a battery of 30 different lectins specific for different carbohydrate residues.
The results indicate that the glandular epithelium of the guinea pig seminal
vesicle exhibits complex glycoconjugates rich in Man, beta-GlcNAc, beta-Gal,
alpha/beta-GalNAc, Fuc and complex NeuAc(alpha2,6)Gal/GalNAc residues, as shown
by its positive reactions to most lectins used. The Golgi region of the luminal
secretory epithelial cells expresses a complex glycoconjugate pattern, as shown
by its strong reactions to Man-(PSA, GNA), beta-GlcNAc-(S-WGA, PWA, DSA, UDA),
beta-Gal-(RCA-I and -II), alpha/beta-GalNAc-(SBA, Jac, VVA, BPA) and complex
NeuAc-(SNA) specific lectins, indicating that the secretory epithelial cells are
active in glycosylation and secretion process. It was also shown in the present
study that the basal and luminal epithelial cells are different in their
glycoconjugates. The basal epithelial cells are rich in NeuAc(alpha2,3)Gal
residues as they are stained specifically by MAA. The fibroblasts in the
epithelial-smooth muscle interface and the smooth muscle cells close to the
glandular epithelium are shown to express more glycoconjugates as they are
stained intensely by GS-I-B4, GS-II and SBA. However, their role in the
epithelial-stromal interaction in the seminal vesicle remains to be elucidated.
In summary, the present study reports for the first time on the lectin binding
patterns of the guinea pig seminal vesicle, and the results show that the seminal
vesicle epithelium elaborates and secretes glycoconjugates in a complex pattern.
Some of the lectins might be useful as histochemical markers for the secretory
activity and specific structural components in the guinea pig seminal vesicle.
PMID- 10192545
TI - Presence of immunoreactive corticotropin-releasing hormone and cortisol molecules
in invertebrate haemocytes and lower and higher vertebrate thymus.
AB - Corticotropin-releasing hormone- and cortisol-like molecules are present in the
haemocytes of different molluscan species and in the epithelial cells,
interdigitating cells and macrophages - but not in the lymphocytes - of fish,
frog, chicken and rat thymus. Taking into account the fact that other pro
opiomelanocortin-derived peptides, such as adrenocorticotropin hormone, are
present in the haemocytes and thymus of the same species, these results complete
the list of stress mediators present in molluscan haemocytes and further support
the hypothesis that, although the prototype stress response we have demonstrated
in invertebrates is concentrated in a single cell, i.e. the haemocyte, it is
similar to the response seen in vertebrates. Moreover, the data presented here
are compatible with the hypothesis that an evolutionary, conserved stress
response can occur locally with a single organ, e.g. the thymus, in which all the
main mediators of this biological response, such as corticotropin-releasing
hormone, adrenocorticotropin hormone and glucocorticoids, are present. The
implications of these findings for the physiology of thymus and stress response
may be far reaching.
PMID- 10192546
TI - Comparative localization of aldehyde oxidase and xanthine oxidoreductase activity
in rat tissues.
AB - The distribution of aldehyde oxidase activity was evaluated in unfixed cryostat
sections from tissues of male Wistar rats using a tissue protectant, polyvinyl
alcohol, with Tetranitro BT as a final electron acceptor. The distribution of
aldehyde oxidase activity was compared with that of xanthine oxidoreductase. The
enzyme histochemical method demonstrated aldehyde oxidase activity in the
epithelium of the tongue, renal tubules and bronchioles, as well as in the
cytoplasm of liver cells. Such activity was not detected in oesophagus, stomach,
spleen, adrenal glands, small or large intestine or skeletal and heart muscle
fibres. In contrast, xanthine oxidoreductase activity was demonstrated in the
tongue, renal tubules, bronchioles, oesophageal, gastric, small and large
intestinal epithelial cells, adrenal glands, spleen and liver cytoplasm but not
in skeletal and heart muscle fibres. The significance of the ubiquitous
distribution of aldehyde oxidase activity, especially in surface epithelial cells
from various tissues, except for the gastrointestinal tract, is unclear. However,
aldehyde oxidase may possess some physiological activity other than in the
metabolism of N-heterocyclics or of certain drugs.
PMID- 10192547
TI - Visualization of vaginal flora in cervical smears using a modified microwave
silver-staining method.
AB - The advantage of studying the vaginal flora to determine the bacteria and fungi
present in cervical smears (as opposed to cultivation of these micro-organisms)
is that the micro-organisms can be observed in their natural habitat. However,
they are only faintly stained by the conventional Papanicolaou method.
Accordingly, contrast is weak and visualization poor. For this reason, we
developed a modified microwave silver-staining method that can be performed
retrospectively on stained smears. Bacteria and fungi stain distinctly black and
can be studied in greater detail, and their inter-relationship can be visualized.
Haematoxylin or Eosin counterstain allows us to visualize vaginal inhabitants in
relation to epithelial cells. In the series presented here, we show that a
modified microwave silver-staining method is well suited to studying the ecology
of micro-organisms in smears taken from women presenting to their doctor with
clinical symptoms. Using this staining method, we have shown that lactobacilli
overgrowth is associated with symptoms.
PMID- 10192548
TI - Differential expression of laminin chains in the human major salivary gland.
AB - Laminin represents a macromolecule family. The heterotrimeric isoforms of laminin
can be determined by immunohistochemical demonstration of the single chains. The
laminin chain heterogeneity of the basement membrane in adult human major
salivary glands was evaluated in relation to cellular differentiation of the
epithelia and the stromal compartment. Monoclonal antibodies to the laminin
alpha1, alpha3 (BM165) chains and epiligrin reacted with the basement membranes
of serous and mucous acini and of intercalated, striated and excretory ducts. As
evidenced by a double-labelling technique, the alpha2 chain showed a spatial
association with the myoepithelium of the acini, whereas the ductal basement
membranes containing no myoepithelial cells were negative. Almost exclusively,
beta1 chain was detected in acinar basement membrane, beta2 chain whereas in
ductal basement membrane. Gamma2 chain is a unique chain belonging to the laminin
5 isoform. It was restricted to the ductal basement membrane. Alpha1, alpha2,
beta1, beta2 and gamma1 chains were detected in nerves of salivary tissue and
alpha1, alpha3, beta1, beta2 and gamma1 chains and epiligrin in blood vessels.
Our results indicate that the acinar ductal unit contains basement membranes with
different isoforms, which relate to cell differentiation and cell function.
PMID- 10192549
TI - Type X collagen in the human invertebral disc: an indication of repair or
remodelling?
AB - The short-chained type X collagen was once thought to be produced exclusively by
hypertrophic chondrocytes during endochondral ossification. More recently,
however, it has been found elsewhere, for example in articular cartilage. In the
present study, the occurrence of type X collagen in the intervertebral disc has
been investigated. Human disc tissues of varying pathologies were examined for
the presence of type X collagen and expression of alpha1(X) mRNA by
immunohistochemistry and in situ hybridization respectively. All samples of disc
contained areas that were immunoreactive but to varying extents. In the disc
itself, staining for the protein and alpha1(X) mRNA was seen frequently
associated with cells of the nucleus pulposus, which were large and of
hypertrophic appearance, most commonly found in degenerate discs, and also in
areas of disorganized architecture, such as clefts. In addition, type X collagen,
both protein and mRNA, was found in regions of the cartilage end-plate, which
calcify ectopically in scoliotic patients. We suggest that type X collagen
production may be a response of disc tissue cells to a stimulus, such as altered
loading.
PMID- 10192550
TI - Enzyme histochemistry of rat mast cell tryptase.
AB - Fixation and staining conditions for rat mast cell tryptase and its histochemical
distribution in different rat tissues were investigated. Prostate, skin, lung,
gut, stomach and salivary glands were fixed in either aldehyde or Carnoy
fixatives and then frozen or embedded in paraffin wax. Preservation of tryptase
enzymic activity against peptide substrates required aldehyde fixation and frozen
sectioning. Of the peptide substrates examined, z-Ala-Ala-Lys-4-methoxy-2
naphthylamide and z-Gly-Pro-Arg-4-methoxy-2-naphthylamide proved the most
effective for the demonstration of tryptase. Double staining by enzyme
cytochemistry followed by immunological detection of tryptase showed that, in all
tryptase-containing mast cells, the enzyme is at least in part active.
Conventional dye-binding histochemistry was used to confirm the identity of mast
cells. Aldehyde-fixed mucosal mast cells required a much shorter staining time
with Toluidine Blue if tissue sections were washed directly in t-butyl alcohol.
Double staining by enzyme cytochemistry and dye binding showed that tryptase is
absent from mucosal and subepidermal mast cells, which are also smaller in size
and appear to contain fewer granules than connective tissue mast cells. This
study demonstrates that rat mast cell tryptase, unlike tryptases in other
species, is a soluble enzyme. It is stored in an active form and is absent from
some mast cell subpopulations in mucosa, skin and lung.
PMID- 10192551
TI - An improved ultrastructural double-staining method for rat growth hormone and its
mRNA using LR White resin: a technical note.
AB - An improved new method for the simultaneous visualization of mRNA and encoded
protein in LR White resin-embedded specimens is described. This pre-embedding
electron microscopical in situ hybridization (procedure) localized rat growth
hormone mRNA specifically as high electron-density products on the polysomes of
the rough endoplasmic reticulum. A subsequent post-embedding immunoreaction,
using protein A colloidal gold particles, identified growth hormone as gold
particles both in the cisternae of the rough endoplasmic reticulum and on the
secretory granules. In our previous report, we used Epon resin for tissue
embedment, which required an etching process using hydrogen peroxide or sodium
periodate for immunoreactivity retrieval. In general, osmification and embedment
in Epon resin are reported to decrease the immunoreactivity of the targeted
protein, and the etching process using hydrogen peroxide or sodium periodate
results in deosmification and shades off the signals of mRNA. To resolve these
problems, we have recently used LR White resin for tissue embedment. In LR White
resin-embedded tissues, retrieval of immunoreactivity using hydrogen peroxide or
sodium periodate is not required, and, therefore, the gradation of the signals of
mRNA can be avoided.
PMID- 10192552
TI - Ultrastructural localization and biochemical characterization of vitronectin in
developing rat bone.
AB - This study has used light and electron microscope immunohistochemical and
biochemical methods to localize and characterize vitronectin in early bone
formation of developing rat mandible with rabbit antimurine vitronectin IgG.
Developing jaws of foetuses were collected at embryonic day 15 (day 15) to day 18
from pregnant Wistar rats. After aldehyde fixation, specimens with and without
osmium post-fixation were dehydrated and embedded in paraffin, Spurr's resin or
LR gold resin for morphological and immunohistochemical examinations. At the
light microscope level, in day 15 samples, positive vitronectin immunostaining
was observed in small elongated areas of intercellular matrix and osteoblasts.
Concomitant with initiation of matrix mineralization at day 16, vitronectin
staining was similarly observed in small elongated areas containing intercellular
matrix and osteoblasts but not clearly detected in fully mineralized bone matrix.
The same staining profile was observed at days 17 and 18. At the ultrastructural
level, immunogold particles were clearly detected over unmineralized matrix and
cisterns of the rough-surfaced endoplasmic reticulum and the Golgi apparatus of
osteoblasts as well as over demineralized bone matrix at day 16-18. In order to
assess the presence of vitronectin in the mineral phase, mineral-binding bone
proteins were extracted from fresh day 18 specimens using a three-step technique:
4M guanidine HCl (G1 extract), aqueous EDTA without guanidine HCl (E extract),
followed by guanidine HCl. Subsequent Western blot analysis of sodium dodecyl
sulphate (SDS)-polyacrylamide gel electrophoresis revealed that the antibodies
produced only a single band at an M(r) of approximately 73000 in both G1 and E
extracts, indicating the presence of vitronectin in the mineralized bone matrix.
These results indicate that, at the onset of bone formation, osteoblasts
synthesize and release vitronectin, which is subsequently incorporated into the
bone matrix and becomes a specific component of bone tissues. The observation of
vitronectin in these critical stages of bone formation suggests that it may be
involved in the regulation of bone formation.
PMID- 10192553
TI - Introduction to special issue on the economics of health insurance in low and
middle-income countries.
PMID- 10192554
TI - Using social health insurance to meet policy goals.
AB - Social health insurance, with contributions based on incomes and access to
services on need is being considered as an option for health care finance in many
countries. The argument in this paper starts from the premise that the choice of
health care financing mechanisms should start with a clear focus on policy goals,
with different options judged against the extent to which these are met. These
are likely to include objectives of access to care for those in need, quality of
care, incentives for efficient provision and cost control. Different systems will
meet the objectives of mobilising resources, providing insurance against risk and
redistribution resources to differing extents. It is argued that a particular
problem in health care finance is shifting rights to resources over time. It is
also important to be clear about the distinction between affordability of and
payment mechanisms for health care. The choice of funding mechanisms may have
little effect on other policy goals, such as economic development. However, they
may differ in the degree to which they allow specific health policy goals to be
met. Different mechanisms for collecting and managing funds, and for paying for
services are discussed. The paper concludes with concerns that too much emphasis
is placed on structures and not how they work, that a lack of cost control may be
a serious risk in developing social health insurance and that it is important to
have clear mechanisms for setting priorities if policy goals are to be met.
PMID- 10192555
TI - Developing health insurance in transitional Asia.
AB - Many European and Asian economies are currently undergoing a process of economic
transition away from state based command systems to market led economies. The
impact of transition, such as a decline in public expenditure, break up of state
enterprises and economic recession, has affected levels of funding available for
social sectors. In the health sector, health insurance is being introduced as a
way of alleviating the decline in funding arising from these processes. Most of
the Former Soviet Union and a number of other Asian transition economies are
currently introducing, extending or considering payroll based systems of health
insurance. Comparisons with many Latin American countries, where social security
based insurance has been encouraged since the first World War, can be
illuminating. Experience suggests that, various factors have impeded or permitted
development in these countries. General processes of economic change (transition
factors) tend to affect all economies attempting to change the basis for public
funding of services. Structural factors, such as urbanisation and the level of
state or industrial employment, act as longer term inhibitors to the extension of
coverage. These factors vary considerably across transition economies. This
suggests that while a social security base for insurance may be a viable option
for smaller industrialised European transitional economies, this is not the case
for many of larger less industrialised economies. It is unclear how insurance
will develop in the future. If a separate insurance fund is maintained it is
important that its' purchasing function is developed. Otherwise it is not clear
what value is added to the current health system. If entitlement is to be based
on contribution, with the fund based on geographic or employment groups, systems
for ensuring access for those not in employment and not classified as socially
protected must be developed.
PMID- 10192556
TI - Social movements and health insurance: a critical evaluation of voluntary, non
profit insurance schemes with case studies from Ghana and Cameroon.
AB - This paper assesses the performance of voluntary, non-profit health insurance
schemes and their potential contribution to health in the two African countries
of Ghana and Cameroon. Based on fieldwork conducted in the two countries during
the main rainy season (June-July) of 1996, the paper examines whether and in
which way the presence or absence of a social movement component might affect the
performance of voluntary, non-profit insurance schemes in attaining some key
objectives of improving access to health care among the target population, as
well as achieving equity, efficiency and financial viability. The paper makes
this assessment by examining the performances of each of two case studies
according to the criteria of social movement, efficiency, equity, access and
financial results. Based on case studies of a community financing insurance
scheme in Ghana and a mutual aid insurance association in Cameroon, the study
concludes that the evidence is not sufficient to confirm that the presence or
absence of such a social movement dynamic per se accounts for the perceived
performance of either of the schemes. However, it is also argued that the dynamic
of social movement could enhance the design and performance of a scheme,
especially the efficiency and quality of health care. Such enhancement is
possible provided that the scheme is set up in such a way as to benefit from the
specific contribution of a movement component, in particular, if the scheme
engages in direct negotiations with providers over the price and quality of care
and makes direct payment contracts with such providers. A good scheme design is
therefore one of the real keys to success. Moreover, it is arguable that a non
social movement based scheme can incorporate elements of a social movement (such
as greater community participation, accountability and autonomy) in the course of
time. It is argued that this process would enhance the success of a non-movement
based scheme. The study finally presents some lessons and suggestions from the
examination of the schemes which could be of benefit in the design,
implementation and evaluation of similar schemes.
PMID- 10192557
TI - The Bwamanda hospital insurance scheme: effective for whom? A study of its impact
on hospital utilization patterns.
AB - The Bwamanda hospital insurance scheme in Zaire was launched in the mid-eighties
and is one of the few well-established and documented initiatives in the field of
district-based insurance schemes in sub-Saharan Africa. It was established that
hospital utilization in Bwamanda is significantly higher among the insured
population. A higher hospital utilization is however not a goal in itself: it is
a positive phenomenon if it takes place for problems where the hospital's know
how and technology are needed to solve the patient's problem. This paper
investigates the effect of the insurance scheme on hospital utilization patterns.
More specifically, the distribution of this higher utilization over the different
hospital departments, as well as its spatial distribution in the entire district
area are analyzed. The impact of the insurance scheme on the effectiveness,
equity and efficiency of hospital utilization are discussed. The relevance and
possible implications of these findings on the design of the Bwamanda insurance
scheme are discussed. Finally, it is argued that the methods used in the present
study contribute to a coherent framework for the evaluation of similar
initiatives.
PMID- 10192558
TI - The social security scheme in Thailand: what lessons can be drawn?
AB - The Social Security Scheme was launched in 1990, covering formal sector private
employees for non-work related sickness, maternity and invalidity including cash
benefits and funeral grants. The scheme is financed by tripartite contributions
from government, employers and employees, each of 1.5% of payroll (total of
4.5%). The scheme decided to pay health care providers, whether public or
private, on a flat rate capitation basis to cover both ambulatory and inpatient
care. Registration of the insured with a contractor hospital was a necessary
consequence of the chosen capitation payment system. The aim of this paper is to
review the operation of the scheme, and to explore the implications of capitation
payment and registration for utilisation levels and provider behaviour. A key
weakness of the scheme's design is suggested to be the initial decision to give
employers not employees the responsibility for choosing the registered hospitals.
This was done for administrative reasons, but it contributed to low levels of use
of the contractor hospitals. In addition, low levels of use were also probably
the result of the potential for cream skimming, cost shifting from inpatient to
ambulatory care and under-provision of patient care, though since monitoring
mechanisms by the Social Security Office were weak, these effects are difficult
to detect conclusively. Mechanisms to improve utilisation levels were gradually
introduced, such as employee choice of registered hospitals and the formation of
sub-contractor networks to improve access to care. A beneficial effect of the
capitation payment system was that the Social Security Fund generated substantial
reserves and expenditures on sickness benefits were well stabilised. The paper
ends by recommending that future policy amendments should be guided by research
and empirical findings and that tougher monitoring and enforcement of quality of
care standards are required.
PMID- 10192559
TI - The potential for social mobilisation in Bangladesh: the organisation and
functioning of two health insurance schemes.
AB - Health insurance schemes are usually assessed according to technical indicators.
This approach, however, neglects the dynamic perspective of insurance schemes as
an element of people's mobilisation for participation in organising and managing
health care delivery and financing. The first part of this paper describes the
technical performance and the level of community involvement in management of the
two largest health insurance schemes in Bangladesh, both in the rural areas and
in the non-government sector. Part two discusses these achievements in light of
the schemes' potential role as a mechanism for people's management of health
care. A review of documents and key-informant interviews were conducted. Key
findings include that (1) subscribers currently are not actively participating in
scheme management. However, existing family groups, involved in credit programmes
may serve as entry-points for interaction. This is sustained by the 'natural
link' between health insurance as a means of spreading the risks of treatment
costs and credit programmes as a means of decreasing the relative impact of
illness on household income. (2) The schemes' role could be further enhanced, by
improving their technical performance and applying health care systems elements
with the input of all partners involved. These issues are avoidance of service
duplication with other providers; better protection of the poorer households;
inclusion of hospital care in the coverage package; simplification of scheme
administration by introduction of episode-based co-payments instead of the
current itemised ones and concentrating the schemes at the level of community
based services, which may be self-financed and also self-managed by the
community, given available sensitisation, training and interaction. A shift to
episode-based co-payments would also introduce solidarity among patients and
among individuals at higher risk, such as pregnant women and under-fives.
Finally, action-research is needed to document the process of increased community
involvement.
PMID- 10192560
TI - NGOs in community health insurance schemes: examples from Guatemala and the
Philippines.
AB - In poor rural communities, access to basic health care is often severely limited
by inadequate supply as well as financial barriers to seeking care. National
policies may introduce social health insurance, but these are likely to begin
with the salaried public and private sector workers while the informal sector
population may be the last to be covered. Community initiatives to generate
health care financing require a complex development process. This paper covers
attempts to develop such schemes in rural populations in Guatemala and the
Philippines through non-government organizations and notes the major factors
which have contributed to unequal progress in the two schemes. The scheme of the
Association por Salud de Barillas (ASSABA) in Guatemala was not sufficiently
established as an administrative body at the conceptual stage and there was no
clear national policy on health care financing. By the time the necessary action
was taken, local conflicts hindered progress. In the Philippines, the ORT Health
Plus Scheme (OHPS) was implemented during the period of legislation of a national
health insurance act. The appraisal after three years of operation shows that
OPHS has made health care affordable and accessible to the target population,
composed mainly of low and often unstable income families in rural areas. The
major success factors are probably the administrative structure provided by a
cooperative and controls in the delivery system and in expenditures, through the
salaried primary health care team, referral process and the capitation agreement
for hospital-based services. The proliferation of such schemes could benefit from
national guidelines, a formal accreditation process and an umbrella organization
to provide assistance in design, training and information services, involving
government, non-government and academic institutions as an integral part of the
development process.
PMID- 10192561
TI - Rural health prepayment schemes in China: towards a more active role for
government.
AB - A large majority of China's rural population were members of health prepayment
schemes in the 1970's. Most of these schemes collapsed during the transition to a
market economy. Some localities subsequently reestablished schemes. In early 1997
a new government policy identified health prepayment as a major potential source
of rural health finance. This paper draws on the experience of existing schemes
to explore how government can support implementation of this policy. The decision
to support the establishment of health prepayment schemes is part of the
government's effort to establish new sources of finance for social services. It
believes that individuals are more likely to accept voluntary contributions to a
prepayment scheme than tax increases. The voluntary nature of the contributions
limits the possibilities for risk-sharing and redistribution between rich and
poor. This underlines the need for the government to fund a substantial share of
health expenditure out of general revenues, particularly in poor localities. The
paper notes that many successful prepayment schemes depend on close supervision
by local political leaders. It argues that the national programme will have to
translate these measures into a regulatory system which defines the
responsibilities of scheme management bodies and local governments. A number of
prepayment schemes have collapsed because members did not feel they got value for
money. Local health bureaux will have to cooperate with prepayment schemes to
ensure that health facilities provide good quality services at a reasonable cost.
Users' representatives can also monitor performance. The paper concludes that
government needs to clarify the relationship between health prepayment schemes
and other actors in rural localities in order to increase the chance that schemes
will become a major source rural health finance.
PMID- 10192562
TI - The reform of the rural cooperative medical system in the People's Republic of
China: interim experience in 14 pilot counties.
AB - During the 1960's and 1970's the Chinese government encouraged the 'rural
cooperative medical systems' (RCMS), in order to ensure access to basic health
care among the rural population. There was a break in the development of the RCMS
in the early 1980's, as a consequence of market economic reforms. These reforms
involved a shift from a communal to a household production system. As a result
the collective way of financing rural health care was more or less abandoned.
However, the government of the People's Republic of China was aware of the need
to provide social protection against health care expenses. In March 1994 the
government initiated a project to reestablish the RCMS. This project was
implemented on a pilot basis in 14 counties of seven provinces. The
reestablishment of the RCMS would be guided by the basic principles of health
insurance. In October 1995, a first mid-term evaluation of the RCMS Project was
held. One of the major research questions concerned the extent to which the RCMS
had reduced the risk of paying health care bills that would otherwise be a burden
on families. This article addresses this question and assesses the results
obtained after two years of RCMS experimental work. A general finding is that the
population structure by occupation and income varies, and that the RCMS has
adapted itself to this variety. It is also confirmed that the burden of health
care costs on families was reduced, more so in some counties than in others, but
this reduction has been modest. The research results indicate that there is ample
room for improvement. The outlook is hopeful, however. At the national level,
there is now systematic thinking about RCMS. The current RCMS work is also having
a considerable influence on other counties that are keen to reestablish the RCMS.
PMID- 10192563
TI - Surgeons and the Internet.
PMID- 10192564
TI - Survey of the impact of randomised clinical trials on surgical practice in
France. French Associations for Research in Surgery (AURC and ACAPEM).
Association Universitaire de Recherche en Chirurgie. Association des Chirurgiens
de l'Assistance Publique pour l'Evaluation Medicale.
AB - OBJECTIVE: To evaluate the impact of randomised clinical trials (RCT) on decision
making and therapeutic policies among general and gastrointestinal surgeons in
France. DESIGN: Telephone questionnaire. SETTING: Multicentre study, France.
SUBJECTS: A random sample of 152 surgeons, mean (SD) age 50 (8) years.
INTERVENTIONS AND MAIN OUTCOME MEASURE: Surgeons were asked 12 questions about
their knowledge of RCT and how trials were conducted; influence of RCT on their
treatment policies; means of obtaining information about treatments; how they
evaluated their own results; whether they were willing to take part in RCT; and
personal details including age, speciality, and type of practice. Surgeons were
stratified according to age and type of practice. RESULTS: 148 questionnaires
were suitable for analysis. 83 surgeons (56%) were under 50 years old, 38 (26%)
were exclusively gastrointestinal surgeons, 82 (56%) worked in private practice,
and 36 (24%) worked in teaching and university hospitals. The rest undertook
mixed duties. When asked to say where they obtained their knowledge about
antibiotics, 91 (61%) referred to RCT; these were mainly hospital-based,
gastrointestinal, and younger surgeons. Asked to name a RCT-based policy, 81
(55%) gave medical rather than operative examples. 80 (54%) had already
participated in a RCT; 79 (53%) said that they were willing to participate in a
RCT that included random allocation of patients (there were no statistically
significant differences in answers according to speciality or type of practice,
although younger surgeons answered "yes" to both questions). Specialised journals
were the main source of information for 115 (78%), and surgeons read a mean of 40
issues/year. 142 (96%) read journals in French and 66 (45%) in English, but this
number fell to 10 (15%) of the 65 surgeons aged 50 or more. Personal experience
was considered a more important source of therapeutic knowledge by older and
specialist surgeons. 109 surgeons (74%) recalled patients during the first month
postoperatively to evaluate their results. CONCLUSIONS: French surgeons,
particularly those aged 50 or over, are not well informed about the nature,
conduct, and value of RCT. Most of their information is acquired through reading
and attending scientific meetings and congresses. Surgeons tended to attach more
importance to the fame of the author than to the conduct of the study. The
overall impact of RCT was weak among the surgeons questioned.
PMID- 10192565
TI - Tumour necrosis factor-alpha and interleukin-10 production in septic patients and
the regulatory effect of plasma.
AB - OBJECTIVE: To investigate the capacity of patients' whole blood to produce
proinflammatory and antiinflammatory cytokines in severe sepsis and to relate
abnormalities to the effect of the patients' plasma on cytokine production in
healthy donor blood. DESIGN: Open, prospective clinical study. SETTING: Teaching
hospital, Germany. PATIENTS: Ten patients in the surgical intensive care unit
with shock and a systemic inflammatory response syndrome (SIRS), a mean APACHE II
score of 27, and dysfunction of at least two organ systems at the time of
investigation, resulting in 70% mortality. MAIN OUTCOME MEASURES: Tumour necrosis
factor-alpha (TNF-alpha) and interleukin-10 (IL-10) concentrations. RESULTS: TNF
alpha and IL-10 production of the whole blood in response to lipopolysaccharide
(LPS) was reduced from 2000 pg/ml to 90 pg/ml and from 9163 pg/ml to 622 pg/ml,
respectively (p < 0.01). When the plasma of these septic patients was added to
the whole blood cells of healthy donors TNF-alpha production decreased by 38% to
1238 pg/ml (p < 0.01) and IL-10 production by 36% to 5857 pg/ml (p = 0.03).
CONCLUSION: The effect of plasma from septic patients on the cytokine production
in healthy donor blood cells paralleled the decreased production of
proinflammatory TNF-alpha and antiinflammatory IL-10 in the whole blood of septic
patients. Efforts to modulate cytokine production in septic patients therefore
need to take account of the signals from the plasma as well as the functional
capacity of the cells.
PMID- 10192566
TI - The cytokines IL-1beta and IL-1 receptor antagonist, IL-2 and IL-2 soluble
receptor-alpha, IL-6 and IL-6 soluble receptor, TNF-alpha and TNF soluble
receptor I, and IL10 in drained and systemic blood after major orthopaedic
surgery.
AB - OBJECTIVE: To measure the concentration of the cytokines interleukin-1beta (IL
1beta), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-10 (IL-10), and
tumour necrosis factor-alpha (TNF-alpha) and the modulators of their function
interleukin-1 receptor antagonist (IL-1Ra), interleukin-2 soluble receptor alpha
(IL-2 sRalpha), interleukin-6 soluble receptor (IL-6sR) and soluble tumour
necrosis factor receptor I (sTNFR-I) in systemic and drained blood for the first
six hours after a major orthopaedic operation. DESIGN: Prospective study.
SETTING: University hospital, Oslo. PATIENTS: 8 patients operated on for thoracic
scoliosis. MAIN OUTCOME MEASURE: Concentrations of IL-1beta, IL-2, IL-6, IL-10,
TNF-alpha, IL-1Ra, IL-2 sRalpha , IL-6sR, and sTNFR-I were measured together with
haemoglobin (Hb) concentration, white cell count (WCC), and differential count in
arterial and drained blood at wound closure and 1, 2, 4, and 6 hours
postoperatively. RESULTS: IL-1beta and IL-6 concentrations increased
significantly in drained blood, whereas that of TNF-alpha increased only in
arterial blood. The modulating factors IL-1Ra, sTNFR-I, and IL-10 were increased
both in arterial and drained blood. IL-6sR had decreased slightly at 6 hours in
drained blood. No IL-2 was found and IL-2 sRalpha decreased simultaneously with
the haemodilution. In arterial blood there was a granulocytosis and in drained
blood a relative lymphocytosis. CONCLUSION: Cytokine responses to surgical trauma
include modulating factors such as soluble receptors and receptor antagonists
that have different responses systemically and locally.
PMID- 10192567
TI - Standard serum concentrations and normal fluctuations of CEA, CA 50 and CA 242
during twelve months in men and women aged 60-64 years without malignant disease.
AB - OBJECTIVE: To establish standard serum concentrations of carcinoembryonic antigen
(CEA), carbohydrate antigen (CA) 50 and CA 242 in cancer-free subjects in the age
group during which cancers are likely to develop. DESIGN: Prospective study.
SETTING: University hospital, Sweden. INTERVENTIONS: Blood samples obtained by
venepuncture on four occasions during one year. MAIN OUTCOME MEASURES:
Consultation with the Regional Cancer Registry to exclude those who had
previously had malignant disease diagnosed or developed cancer during and up to
two years after the end of the clinical part of the study. Serum concentrations
of CEA, CA 50, and CA 242. RESULTS: The 90th centile was 5.6 ng/ml for CEA, 30.1
U/ml for CA 50, and 24.5 U/ml for CA 242. The mean (SD) serum concentrations were
2.6 ng/ml (2.2) for CEA, 13.2 U/ml (11.4) for CA 50, and 10.6 U/ml (9.6) for CA
242. Serum concentrations of CEA were significantly higher (p < 0.001) among
smokers. The intraindividual fluctuations were 16%, 16%, and 14%, respectively.
CONCLUSIONS: Serum concentrations of CEA, CA 50, and CA 242 were higher in this
study than previously reported, probably because the subjects were older than in
other reports. The fluctuations were small. Serum concentrations of CEA were
higher in smokers than in non-smokers.
PMID- 10192569
TI - Improved physical condition by limiting lymphadenectomy around the coeliac artery
after distal gastrectomy for gastric cancer.
AB - OBJECTIVE: To find out whether a less extensive lymphadenectomy could relieve the
postoperative symptoms associated with D2 resection of gastric cancer. DESIGN:
Retrospective study. SETTING: Teaching hospital, Japan. SUBJECTS: 142 patients
who had dissection along the left gastric and common hepatic arteries and
dissection of the perigastric nodes during curative distal gastrectomy without
splenectomy or pancreatectomy between 1990 and 1994. 79 who had no dissection
around the coeliac artery were compared with 63 who had. INTERVENTIONS:
Questionnaires sent out in February 1996. MAIN OUTCOME MEASURES: Short term and
long term morbidity. RESULTS: The patients who had had coeliac dissection were
significantly more likely to prefer digestible and light food (p = 0.006); and
were significantly more likely to complain of diarrhoea (p = 0.001), abdominal
pain (p = 0.02), and late dumping (p = 0.03) than those who did not. Patients who
had had coeliac dissection tended to eat more digestible foods in smaller
volumes/meal during the early postoperative years, and had more abdominal pain,
fullness, and oesophageal reflux during the later years. CONCLUSION: Limiting
coeliac dissection during curative distal gastrectomy can improve the patients'
physical condition postoperatively.
PMID- 10192568
TI - Postoperative suction drainage of the axilla: for how long? Prospective
randomised trial.
AB - OBJECTIVE: To define the correct time to remove the drain after axillary
dissection for carcinoma of the breast. DESIGN: Prospective randomised trial.
SETTING: Two public hospitals, Israel. SUBJECTS: 90 women who required axillary
dissection for carcinoma of the breast. INTERVENTIONS: 42 were randomised to have
the drain removed on postoperative day 3, and 48 to keep the drain in until
discharge had decreased to less than 35 ml/24 hours. MAIN OUTCOME MEASURES:
Formation of seromas or wound infections, need to reinsert the drain, and
duration of hospital stay. RESULTS: Early removal of the axillary drain was
associated with a significantly higher incidence of seromas (9/42 compared with
2/48, p = 0.02) unless the total amount of fluid drained during the first three
postoperative days was less than 250 ml. CONCLUSION: Drains should be removed
after axillary dissection only when the daily amount of fluid discharged is low,
unless the drainage during the first three days is less than 250 ml.
PMID- 10192570
TI - Surgical treatment and outcome after delayed diagnosis of blunt duodenal injury.
AB - OBJECTIVE: To review our experience of 18 patients with duodenal injuries after
blunt trauma, the diagnosis of which had been delayed for more than 24 hours.
DESIGN: Retrospective study. SETTING: Teaching hospital, Taiwan, R.O.C. SUBJECTS:
18 patients who presented with duodenal injuries between January 1986 and
December 1995. MAIN OUTCOME MEASURES: Morbidity and mortality. RESULTS: The
reasons for the delay were: injuries not found during the first operation (n =
6), patients had not sought medical help (n = 6), and injuries treated
conservatively at local hospitals (n = 5). There was one delay in our department
because the patient lost consciousness. 12 patients were treated by pyloric
exclusion with no deaths and four complications (one duodenal fistula and 3
retroperitoneal abscesses). The other 6 had various operations including
pancreaticoduodenectomy, jejunostomy, and gastrostomy, with six complications and
one death, giving an overall mortality of 6% and morbidity of 50%. Three patients
developed delayed extensive retroperitoneal abscesses and all three were treated
successfully by laparostomy. 16 of the 18 patients required enteral feeding
through a jejunostomy. CONCLUSIONS: Though the complication rate was high, the
use of pyloric exclusion and a feeding jejunostomy kept the mortality low.
Enteral nutrition should be started early. Laparostomy is a good way to manage
retroperitoneal abscesses. To avoid delay, patients at risk of duodenal injuries
should be evaluated early by experienced trauma surgeons and any central
retroperitoneal haematoma should be explored during the initial laparotomy.
PMID- 10192571
TI - Loop ileostomy: technical aspects and complications.
AB - OBJECTIVE: To study the incidence of complications of construction and closure of
loop ileostomies and the final outcome for the patients. DESIGN: Retrospective
study. SETTING: University hospital, Norway. SUBJECTS: 100 patients with 103 loop
ileostomies, operated on between 1980 and 1990. MAIN OUTCOME MEASURES: Number of
complications after ileostomy construction and closure. RESULTS: 7 required re
operation after construction of the loop ileostomy and 11 after its closure. The
most common cause was small intestinal obstruction (4 after construction and 6
after closure). 2 developed stomal necrosis. The mean duration of hospital stay
was 13 and 10 days for primary and secondary loop ileostomy, respectively, and
the mean time before closure was 31 weeks. After closure another 6 developed
leaks from the ileal anastomosis that required further operation. Patients with
secondary loop ileostomies had their stomas significantly longer than those with
primary loop ileostomies (21 compared with 43 weeks, p = 0.00005). CONCLUSION:
Despite the number of complications, we think that faecal diversion is still
justified in complex pelvic surgery and we should try to reduce the complication
rate further.
PMID- 10192572
TI - Neoperitoneal formation after implantation of various biomaterials for the repair
of abdominal wall defects in rabbits.
AB - OBJECTIVE: To study the interfaces between the visceral peritoneum and some of
the biomaterials used to repair defects in the abdominal wall. DESIGN: Animal
study. SETTING: School of medicine, Spain. MATERIAL: 48 New Zealand white rabbits
divided into 4 groups of 12 each. INTERVENTIONS: Full thickness defects 50 x 70
mm were created in the abdominal wall and repaired with polytetrafluoroethylene
(PTFE, Soft Tissue Patch), one of two polypropylene patches (Marlex and Prolene),
or lyophylised dura mater (Lyo-Dura). 3 animals from each group were killed at
14, 30, 60 and 90 days and specimens examined by light microscopy, scanning
electron microscopy, and immuno histochemistry by labelling of macrophages with
RAM-11, a specific monoclonal antibody (MoAb). MAIN OUTCOME MEASURES: Infection,
healing, development of adhesions, and histological appearance of the interface.
RESULTS: Tissues responded similarly to materials of similar structures. Layered
prostheses (PTFE and Lyo-Dura) caused formation of a well organised neoperitoneum
with few adhesions to the abdominal viscera (loose adhesions in 2 animals in each
group), whereas the mesh prostheses generated a disorganised neoperitoneum with
many adhesions (Marlex loose adhesions 3, firm 8, and integrated 1; Prolene loose
adhesions 2, firm 8, and integrated 2). Lyo-Dura was associated with the
formation of areas of calcification. Labelling of macrophages with the MoAb
showed that they were in direct contact with all materials studied. CONCLUSIONS:
Layered biomaterials with little or no porosity (PTFE and Lyo-Dura) are the most
suitable of the four for implantation in sites where the prosthesis is in contact
with the visceral peritoneum, because they induce minimal adhesions.
PMID- 10192573
TI - The use of a dura mater patch to cover oesophageal defects of different sizes: an
experimental study in chickens.
AB - OBJECTIVE: To find out the optimal size of full thickness oesophageal defects
that can be repaired with patches of Tutoplast Dura (solvent dehydrated human
dura mater in the form of absorbable collagen). DESIGN: Experimental study.
SETTING: Teaching hospital, Greece. MATERIAL: 96 female Hubbard chickens in four
groups of 24. INTERVENTIONS: In the three experimental groups longitudinal
defects were made in the cervical oesophagus 30 x 5, 10, or 15 mm and covered
with Tutoplast. Subgroups of 6 chickens were weighed, had a barium swallow
examination, and were then killed at 2, 4, 6, and 8 weeks. The oesophagus was
removed and examined histopathologically. MAIN OUTCOME MEASURES: Weight, extent
of healing macroscopically and microscopically. RESULTS: All chickens that had
had defects 30 x 15 mm in size died between days 5 and 10, and the oesophagus in
all cases was obstructed by food. There were no deaths or complications in the
other three groups, and no evidence of dysphagia on barium swallow. In chickens
with defects of 30 x 5 and 30 x 10 mm the prosthetic material gradually
disappeared, and they healed well. CONCLUSIONS: Defects in the chicken's cervical
oesophagus larger than 30 x 10 mm cannot be repaired with a Tutoplast patch, but
smaller defects can. Further studies are needed to clarify the mechanisms of
healing.
PMID- 10192574
TI - Value of diagnostic laparoscopy in tuberculous peritonitis.
AB - OBJECTIVE: To assess the safety and efficacy of diagnostic laparoscopy in
patients with tuberculous peritonitis. DESIGN: Retrospective clinical study.
SETTING: University hospital, Turkey. SUBJECTS: 8 patients (2 women, 6 men; mean
age 26 years) who presented with tuberculous peritonitis between January 1994 and
January 1996. INTERVENTION: Laparoscopy under local anaesthesia with sedation
(the 4 who presented with ascites) and laparotomy (the 4 who presented with an
acute abdomen). MAIN OUTCOME MEASURES: Clinical and laboratory findings,
biochemical and microbiological analysis of ascites, histopathological
examination of specimens, morbidity, and mortality. RESULTS: 4 patients presented
with ascites, and 4 with adhesions. Ascites; adhesions between liver and
diaphragm, liver and intestines, and intestines and the abdominal wall; miliary
nodes on the peritoneal surface; and inflamed haemorrhagic areas on the
peritoneum could all be seen at laparoscopy. One of the 8 patients who underwent
laparotomy developed a spontaneous enterocutaneous fistula during the early
postoperative period. Two of eight patients died, one of an early enterocutaneous
fistula and the other of cor pulmonale 3 1/2 months later. The remaining 6
patients survived without complications after antituberculous medical treatment.
CONCLUSIONS: Laparoscopy is a safe and accurate method of diagnosis of
tuberculous peritonitis.
PMID- 10192575
TI - Benign chondrolipomatous tumour of the breast.
PMID- 10192576
TI - Mesenteric thrombosis and factor V Leiden.
PMID- 10192577
TI - "Tubalithiasis"; a late complication of laparoscopic cholecystectomy with stone
spillage.
PMID- 10192578
TI - Hydatid disease: surgeons struggling to treat a medical problem.
PMID- 10192579
TI - Neuropathological sequelae of traumatic injury in the brain. An overview.
AB - The identification and interpretation of brain damage resulting from head injury
is often not easy. The most obvious structural damage, which is identified post
mortem by neuropathologists, may not be the most reliable alteration with regard
to clinico-pathological correlations. For example patients with a fracture of the
skull, a severe cerebral contusion or a large intracerebral hematoma that is
successfully treated can lead to a complete recovery if no other types of brain
damage are present. Thus more subtle forms of pathology, which are often present
and some of which can only be identified microscopically, may be more important.
It is therefore necessary to get deeper insights into the consequences of brain
injury. Though of course not exclusively, this aim can be reached by autopsy.
Primary traumatic brain lesions result immediately from mechanical injury.
Secondary alterations injuries develop through intracranial and extracranial
trauma sequelae, which determine the course and outcome of brain damage.
Traumatic brain damage can be classified as focal or diffuse. It may sometimes be
difficult to distinguish traumatic from ischemic brain injury. One difference,
however, is that the initial events of trauma involve mechanical distortion of
the brain. Mechanoporation as traumatic defect in the cell membrane has recently
been found to be one of the first steps which leads via ionic influxes to the
activation of immediate early genes. Oxygen radicals and cell membrane lipid
peroxidation occur also very early. Increased intracellular calcium, activation
of phospholipases and calpains furthermore damage the membrane and cytoskeleton
and block the axoplasmatic transport, by which delayed cell death can appear. For
the description of the extent of traumatically induced brain damage and the
possible clinico-pathological correlations it is necessary to take these
alterations into consideration as specifically as possible. Neuropathology can
contribute to this aim.
PMID- 10192580
TI - Evaluation of micro tip pressure transducers for the measurement of intracerebral
pressure transients induced by fluid percussion.
AB - We describe the application of MIKRO TIP miniature pressure transducers (MPT) for
the in vivo measurement of intracerebral stresses induced by traumatic brain
injury (TBI). In order to test the linearity of these transducers pressure pulses
of different amplitudes (duration approximately 10ms) were generated in a closed
calibration chamber. A piezoelectric pressure transducer (PPT) served as the
reference measure. A linear correlation was found within the pressure range
between 0.57 and 5.09 bar (R2 = 0.998). The frequency transmission
characteristics of the MPTs are comparable to the PPT. In three juvenile swines
(6 weeks of age) pressures within the brain tissue were induced by fluid
percussion (FP) and were measured in the anterior, middle, and posterior cranial
cavity as well as in the extracranial part of the medulla oblongata. The data
obtained in our experiments agree with the basic biomechanics of FP known from
studies in cats and rabbits. Due to their small size, MPTs can be applied in
living animals. Stereotaxic positioning of these catheters at any site of the
brain and spinal cord requires only minimal surgery. Therefore, MPTs are useful
in evaluating animal models of brain injury and in generating input data for
computational models of head injury as well as to validate the mathematical
results of such models with experimental data.
PMID- 10192581
TI - Animal models of traumatic brain injury in the immature: a review.
PMID- 10192582
TI - Cerebral hemodynamics after traumatic brain injury of immature brain.
AB - These studies were designed to characterize the cerebral hemodynamic effects of
fluid percussion brain injury (FPI) in the newborn pig equipped with a closed
cranial window. Reductions in cerebral blood flow, pial artery diameter, and
cerebral oxygenation following FPI were greater in newborn (1-3 days old) vs.
juvenile (3-4 weeks old) pigs, suggesting that newborns were exquisitely
sensitive to brain injury. Additionally, in piglets, there was decremented
dilation to nitric oxide, cGMP, and cAMP dependent stimuli following FPI. The
membrane potential of vascular muscle is an important contributor to vascular
tone and the activity of K+ channels is an important regulator of membrane
potential. Recent studies indicate that altered dilator responsiveness and
cerebral hemodynamic control following FPI results from impaired K+ ATP sensitive
(KATP) and calcium sensitive (Kca+2) channel function. Impaired KATP channel
function results, at least in part, from protein kinase C activation by the
peptide endothelin-1. These observations indicate that the effects of brain
injury on cerebral hemodynamics in the newborn are multifaceted and
multifactorial.
PMID- 10192583
TI - Ontogenetic aspects of traumatic brain edema--facts and suggestions.
AB - Diffuse brain swelling (DBS) after severe traumatic brain injury (TBI) occurs
more commonly in children than adults. Most of the recent clinical studies
suggest that young children are more negatively affected by DBS. Until now
studies in young animals in which the pathophysiology of DBS was evaluated
remained seldom. However, pathogenetic mechanisms of edema formation after TBI in
the immature brain appeared to be different in comparison to adult brains. There
are evidences that vasogenic as well as cytotoxic edema components may be
responsible for the development of DBS. Besides mechanical disturbance, the blood
brain barrier seems to be strongly endangered by oxidative stress after TBI
because regional antioxidative capacity is obviously diminished. In addition,
cytotoxic components of DBS may be caused by at least two different mechanisms.
First, it was shown that a sustained posttraumatic cerebral hypoperfusion occurs
in the immature brain. Moreover, a transient increase of NMDA receptor expression
at this period of life may be responsible for an increased threat of
intracellular sodium ion accumulation in brain cells. Obviously, brain swelling
can be detrimental because it can elevate intracranial pressure, impair CBF, and
may represent ongoing secondary brain injury.
PMID- 10192584
TI - Poor outcome after hypoxia-ischemia in newborns is associated with physiological
abnormalities during early recovery. Possible relevance to secondary brain injury
after head trauma in infants.
AB - "Secondary hypoxia/ischemia" (i.e. regional impairment of oxygen and substrate
delivery) results in secondary deterioration after traumatic brain injury in
adults as well as in children and infants. However, detailed analysis regarding
critical physiological abnormalities resulting from hypoxia/ischemia in the
immature brain, e.g. acid-base-status, serum glucose levels and brain
temperature, and their influence on outcome, are only available from non
traumatic experimental models. In recent studies on hypoxic/asphyxic cardiac
arrest in neonatal piglets, we were able to predict short-term outcome using
specific physiologic abnormalities immediately after the insult. Severe acidosis,
low serum glucose levels and fever after resuscitation were associated with an
adverse neurologic recovery one day after the insult. The occurrence of
clinically apparent seizure activity during later recovery increased mortality
(epileptic state), and survivors had greater neocortical and striatal brain
damage. Brain damage after transient hypoxia/ischemia and "secondary brain
injury" after head trauma may have some mechanistic overlap, and these findings
on physiological predictors of outcome may also apply to pathologic conditions in
the post-traumatic immature brain. Evaluation of data from other models of brain
injury will be important to develop candidate treatment strategies for head
injured infants and children and may help to initiate specific studies about the
possible role of these physiological predictors of brain damage in the
traumatically injured immature brain.
PMID- 10192585
TI - Hypothermia related changes in electrocortical activity at stepwise increase of
intracranial pressure in piglets.
AB - Recent experimental studies have demonstrated that mild hypothermia can be
effective in the control of intracranial hypertension. However, investigations to
analyze the effects of hypothermia on changes in brain oxygen metabolism and
electrocortical activity caused by increased intracranial pressure (ICP) are
lacking. We examined the effects of mild hypothermia on electrocorticogram (ECoG)
in combination with measurement of regional cerebral blood flow (CBF) and
estimation of brain oxygen metabolism during stepwise increase of ICP. For this
purpose thirteen female piglets (14 days old, 4-5 kg b.w.) were anaesthetized and
mechanically ventilated. An epidural balloon was gradually inflated in order to
increase ICP to 25 mmHg, 35 mmHg and 45 mmHg every 30 minutes at adjusted mean
arterial blood pressures (MAP). This procedure resulted in gradual cerebral
perfusion pressure (CPP) reduction of about 70%, 50%, and 30% of baseline
[baseline CPP: normothermia (NT) 80+/-3 mmHg; hypothermia (HT) 84+/-3 mmHg].
Control animals were maintained in a normothermic state (38.6+/-0.2 degrees C).
HT animals were surface cooled and maintained at 31.9+/-0.1 degrees C. ECoG,
regional CBF, cerebral oxygen delivery (cDO2) and the cerebral metabolic rate of
oxygen (CMRO2) were estimated during the normothermic period, after hypothermic
stabilization, and after the gradual CPP reductions. The baseline ECoG showed the
typical delta-dominated frequency pattern for isoflurane anaesthesia. At the
hypothermic level, a frequency shift was seen from delta activity towards the
higher frequencies (theta- and alpha activity) and the total spectral power was
significantly reduced (56+/-17% from baseline, p < 0.05). the cortical CBF
decreased markedly to 67+/-10% (p < 0.05), whereas the medulla oblongata blood
flow increased slightly. During controlled increase of ICP by regional mass
expansion from epidural balloon inflation, we found at mild and moderate stages
of ICP increase (25 and 35 mmHg) only minimal changes in the ECoG in hypothermic
animals compared to the hypothermic baseline, whereas the ECoG in normothermic
animals showed a marked decrease in frequency, amplitude and total spectral
power. We conclude that mild hypothermia produces an arousal-like ECoG activity
with marked frequency shift to alpha activity and a change from high to low
voltage activity. Furthermore, the hypothermic brain showed a preserved neuronal
function at moderate stages of ICP. Obviously, hypothermia improves the
functional tolerance of the brain to impaired oxygen supply.
PMID- 10192586
TI - Age-specific therapy for traumatic injury of the immature brain: experimental
approaches.
PMID- 10192587
TI - Repeated 4-week inhalation exposure of rats: effect of low-, intermediate, and
high-humidity chamber atmospheres.
AB - A subacute nose-only inhalation study with low (approximately 3%), medium
(approximately 40%), and high humidity (approximately 80%) has been performed on
young adult Wistar rats. Exposure was 6-hr/day on 5 days/week for 4 consecutive
weeks. Rats housed individually in the animal holding room, deprived of feed and
water during exposure of the remaining groups, served as concurrent controls
(sham controls). This study served the purpose to assess whether toxicologically
significant effects occur when rats are repeatedly exposed to lower or higher
humidity chamber atmospheres than proposed by current testing guidelines. For
analysis, conventional end-points as required by common testing guidelines were
considered, i.e., clinical observations before and after exposure, rectal
temperatures, body weights, feed and water consumption. At the end of the 4-week
exposure period, ophthalmological and gross pathological examinations were made
and major organ weights determined. The histopathological examinations comprised
the nasal cavities, larynx, trachea, and lungs. There was no apparent evidence of
humidity-related effects on nose-only exposed rats. When compared with non
exposed sham controls, however, body weights, water and feed consumption were
markedly reduced in all nose-only exposure groups. In summary, it can be
concluded that rats tolerated either humidity atmosphere without any specific
effects. As far as there were differences to sham controls they appear to be more
controlled by the differences in the exposure patterns (nose-only versus normal
housing) than differences in the humidity of chamber atmospheres. Thus,
deviations of current testing guidelines for repeated exposure inhalation studies
with regard to humidity, do not appear to have any appreciable impact on the
study outcome.
PMID- 10192588
TI - Peptides and psychiatry, Part 3: substance P and serendipity: novel psychotropics
are a possibility.
PMID- 10192589
TI - The Texas Medication Algorithm Project: report of the Texas Consensus Conference
Panel on Medication Treatment of Major Depressive Disorder.
AB - BACKGROUND: This article describes the development of consensus medication
algorithms for the treatment of patients with major depressive disorder in the
Texas public mental health system. To the best of our knowledge, the Texas
Medication Algorithm Project (TMAP) is the first attempt to develop and
prospectively evaluate consensus-based medication algorithms for the treatment of
individuals with severe and persistent mental illnesses. The goals of the
algorithm project are to increase the consistency of appropriate treatment of
major depressive disorder and to improve clinical outcomes of patients with the
disorder. METHOD: A consensus conference composed of academic clinicians and
researchers, practicing clinicians, administrators, consumers, and families was
convened to develop evidence-based consensus algorithms for the pharmacotherapy
of major depressive disorder in the Texas mental health system. After a series of
presentations and panel discussions, the consensus panel met and drafted the
algorithms. RESULTS: The panel consensually agreed on algorithms developed for
both nonpsychotic and psychotic depression. The algorithms consist of systematic
strategies to define appropriate treatment interventions and tactics to assure
optimal implementation of the strategies. Subsequent to the consensus process,
the algorithms were further modified and expanded iteratively to facilitate
implementation on a local basis. CONCLUSION: These algorithms serve as the
initial foundation for the development and implementation of medication treatment
algorithms for patients treated in public mental health systems. Specific issues
related to adaptation, implementation, feasibility testing, and evaluation of
outcomes with the pharmacotherapeutic algorithms will be described in future
articles.
PMID- 10192590
TI - The effects of venlafaxine on social activity level in depressed outpatients.
AB - BACKGROUND: Although most depression treatment outcome scales focus on symptoms,
depression also affects daily functioning, social activity, and quality of life.
We examined the effects of venlafaxine on social activity, general life
functioning, and depressive symptoms in 2 placebo-controlled clinical trials of
venlafaxine. METHOD: Subjects were 600 outpatients with major depression (DSM-III
R criteria). Treatment outcomes were examined separately in each study, primarily
because of differing lengths of follow-up. RESULTS: Treatment with venlafaxine
significantly improved activity level, general life functioning, and depressive
symptoms. Treatment accounted for statistically significant changes in both
activity level and general life functioning even after controlling for changes in
depression. CONCLUSION: We provide evidence that social activity is a behavioral
domain distinct from depressive symptoms and that venlafaxine improves social
activity level and general life functioning in addition to its positive effects
on depressive symptoms in outpatients with major depression.
PMID- 10192591
TI - The pharmacotherapy of depressive illness in adolescents: an open-label
comparison of fluoxetine with imipramine-treated historical controls.
AB - BACKGROUND: This open-label, 6-week clinical trial investigated the response to
fluoxetine in medication-naive adolescents hospitalized for treatment of major
depression. METHOD: A total of 52 consecutively admitted patients (mean age =
15.7 years) fulfilling Research Diagnostic Criteria for unipolar, nonpsychotic
major depression received fluoxetine monotherapy (mean dose = 33.2 mg/day) in
conjunction with psychosocial therapies. Outcome was assessed weekly using the
Hamilton Rating Scale for Depression (HAM-D) and the Clinical Global Impressions
Scale (CGI). Response in this cohort was compared with that observed in 28
historical controls treated with imipramine (mean dose = 217 mg/day) who were
consecutively admitted patients to this same facility and assessed in an
identical, standardized, open-label protocol. RESULTS: HAM-D scores decreased by
a mean of 13.2 in the fluoxetine group compared with 10.2 in the group receiving
imipramine (p<.002). The mean percentage decreases in HAM-D scores in the 2
groups were 54.3% and 41.4%, respectively (p<.003). The percentages of patients
classified as responders based on a final CGI score of 2 or less were 48.1% and
17.9%, respectively (p = .009). Medications were generally well tolerated with
only 5 patients failing to complete the full 6 weeks of their original treatment.
CONCLUSION: In spite of the uncontrolled nature of these data, the findings add
to recent evidence suggesting more favorable response to selective serotonin
reuptake inhibitors than tricyclics in adolescents with depressive illness.
PMID- 10192592
TI - Sexual offending and antisocial sexual behavior among patients with
schizophrenia.
AB - BACKGROUND: A number of studies have indicated excessive offending behavior among
people with schizophrenia; however, sexual offending has not been widely
described. METHOD: This study reports on a subgroup of 15 men with schizophrenia,
diagnosed according to ICD-10 guidelines, in a secure hospital who had committed
sexual offenses or shown antisocial sexual behavior. A comparison group comprised
55 male patients with schizophrenia and a history of violent behavior who were
being treated in the same hospitals as the study group. RESULTS: In 12 of the 15
cases, the sexual offending/behavior postdated illness onset and occurred in the
context of psychotic symptoms. Although 12 of the offenders were known to
psychiatric services, contact was erratic and only 4 were taking medication. At
assessment, those with sexual offenses or antisocial sexual behavior were twice
as likely as the larger study sample to report unimpaired sexual interest. This
may be of particular relevance in that the group also reported difficulty in
forming close personal relationships. CONCLUSION: Illness-related factors appear
to make an important contribution to sexual offending by this group of patients,
highlighting the need for comprehensive and vigorous treatment.
PMID- 10192593
TI - Obsessions and compulsions in women with postpartum depression.
AB - OBJECTIVE: The quantity, content, and intensity of the obsessions and compulsions
of women with postpartum onset major depressive disorder were compared with those
of women with major depressive disorder with non-postpartum onset. METHOD:
Sequential cases of women with postpartum onset major depression (N = 37) and
major depression (N = 28) who presented to our Women's Mood Disorders program
were included. Psychiatric examination using DSM-IV criteria and the Inventory to
Diagnose Depression established the diagnosis of major depression. Obsessive
thoughts and compulsions were reported on the Yale-Brown Obsessive Compulsive
Scale and reviewed during the psychiatric examination. Comparisons between groups
were performed with chi-square statistics, Fisher exact test and its extensions,
and Mann-Whitney U test. RESULTS: Although more women with postpartum onset major
depression (N = 21, 57%) than major depression (N = 10, 36%) reported obsessional
thoughts, the difference between the groups was not significant (p = .13).
However, for women who endorsed obsessions, those with postpartum onset had a
higher median number (median = 7) than women without postpartum onset (median =
2, p = .00). Most of the difference in frequency of thoughts was owing to more
women with postpartum onset major depression having aggressive thoughts (N = 20,
95%) than women with major depression (N = 6, 60%, Fisher exact p = .03). The
most frequent content of the aggressive thoughts for women with postpartum onset
major depression was causing harm to their newborns or infants. The presence or
number of obsessional thoughts or compulsions was not related to severity of the
depressive episode. CONCLUSION: Childbearing-aged women commonly experience
obsessional thoughts or compulsions in the context of major depressive episodes.
Women with postpartum onset major depression experience disturbing aggressive
obsessional thoughts more frequently than women with non-postpartum major
depression.
PMID- 10192594
TI - Efficacy of lithium vs. valproate in the treatment of mania in the elderly: a
retrospective study.
AB - BACKGROUND: This retrospective study was conducted to assess the efficacy of
lithium and valproate and associated serum levels in the treatment of mania in
elderly patients. METHOD: Records of 59 patients aged 55 years and older with
minimal or no neurologic impairment, hospitalized for mania, and discharged on
lithium (N = 30) or valproate (N = 29) therapy were reviewed. Data on mood
stabilizer choice, serum levels, and type of mania were recorded. A clinician
blinded to medications rated improvement in each case with Clinical Global
Impressions (CGI) scores based on abstracted notes. RESULTS: Overall, the
percentage of patients improved was significantly greater in the lithium group
than in the valproate group (67% vs. 38%, chi2 = 4.88, p = .027). Patients taking
lithium with serum levels > or =0.8 mmol/L were more improved at discharge than
those outside this range (> or =0.8, CGI 2.0+/-0.6 vs. <0.8, CGI 2.6+/-0.8, t =
2.15, p = .043). Patients taking valproate with serum levels between 65-90
microg/mL were more improved at discharge than those outside this range (65-90,
CGI 2.1+/-0.6 vs. <65, >90, CGI 3.3+/-0.8, t = 3.73, p = .002). When response
rates among only patients with these "therapeutic" levels were assessed, they
were similar for lithium (82%) and valproate (75%). The difference in efficacy
between drugs was maintained in classic mania, but the 2 drug groups were similar
when only mixed mania was analyzed (lithium 63% vs. valproate 67% improved).
CONCLUSION: Results suggest that lithium may be more efficacious than valproate
overall, but response rates for the 2 drugs were similar when "therapeutic" serum
levels were achieved. For lithium, levels similar to those reported for younger
adults were associated with response. For valproate, a "therapeutic window"
different from that in younger adults was found. While the retrospective and
naturalistic design of this study has limitations, these data may help direct
further studies and treatment of mania in the elderly.
PMID- 10192595
TI - Incidence of sexual dysfunction in healthy volunteers on fluvoxamine therapy.
AB - BACKGROUND: Current literature suggests that the incidence of sexual dysfunction
secondary to fluvoxamine therapy is 1% to 8%, while other selective serotonin
reuptake inhibitors may have rates as high as 75%. The objective of this study
was to determine the incidence of sexual dysfunction secondary to fluvoxamine in
healthy volunteers. METHOD: 20 healthy volunteers (10 men, 10 premenopausal
women) had adverse effects assessed at 6 visits while not receiving fluvoxamine,
then twice while taking 150 mg fluvoxamine daily. Assessments occurred at 2-week
intervals. Incidence rates for sexual dysfunction were calculated. RESULTS: No
sexual dysfunction was reported prior to fluvoxamine therapy. After 2 weeks and 4
weeks of therapy respectively, sexual dysfunction occurred in 20% (N = 4) and 35%
(N = 7) of the healthy volunteers. CONCLUSION: The incidence of sexual
dysfunction during fluvoxamine therapy in healthy volunteers is 35%. This
incidence is higher than previously reported and similar to that of other
selective serotonin reuptake inhibitors.
PMID- 10192596
TI - Refining the MAOI diet: tyramine content of pizzas and soy products.
AB - BACKGROUND: Continuous refinement of the monoamine oxidase inhibitor (MAOI) diet
has resulted in much reduced and simplified recommendations that attempt to
balance safety and practicality. In the spirit of evidence-based practice,
dietary restrictions should be based on carefully documented case reports and
valid tyramine analyses. Residual concerns have focused on combination foods such
as pizza and a variety of soy products. We determined the tyramine content of
pizzas and a variety of soy products in order to refine dietary recommendations
for use with MAOIs. METHOD: High-pressure liquid chromatography analysis of
tyramine content was performed on a variety of pizzas, soy sauces, and other
soybean products. A tyramine level of 6 mg or less was considered safe. RESULTS:
No significant tyramine levels were found in any of the pizzas, including those
with double pepperoni and double cheese. Marked variability was found in soy
products, including clinically significant tyramine levels in tofu when stored
for a week and high tyramine content in one of the soy sauces. CONCLUSION: Pizzas
from large chain commercial outlets are safe for consumption with MAOIs. However,
caution must be exercised if ordering pizzas from smaller outlets or gourmet
pizzas known to contain aged cheeses. All soybean products should be avoided,
especially soy sauce and tofu. Individualized counseling and continuous
surveillance of compliance are still essential.
PMID- 10192597
TI - Sildenafil treatment of serotonin reuptake inhibitor-induced sexual dysfunction.
PMID- 10192598
TI - Treatment of intermittent explosive disorder with sertraline in 3 patients.
PMID- 10192599
TI - Bupropion clarification.
PMID- 10192600
TI - Suicide victims with schizophrenia in different treatment phases and adequacy of
antipsychotic medication.
AB - BACKGROUND: To investigate clinical characteristics and adequacy of antipsychotic
treatment in different phases of illness and treatment among suicide victims with
schizophrenia. METHOD: As part of the National Suicide Prevention Project, a
nationwide psychological autopsy study in Finland, all DSM-III-R schizophrenic
suicide victims with a known treatment contact (N = 88) were classified according
to the phase of illness (active/residual) and treatment (inpatient/recent
discharge/other). Characteristics of victims in terms of known risk factors for
suicide in schizophrenia, as well as adequacy of the neuroleptic treatment, were
examined. RESULTS: Fifty-seven percent of suicide victims with active phase
schizophrenia were prescribed inadequate neuroleptic treatment or were non
compliant, and 23% were estimated to be compliant nonresponders. Inpatient
suicide victims had the highest proportion of negative or indifferent treatment
attitudes (81%), whereas recently discharged suicide victims had the highest
prevalence of comorbid alcoholism (36%), paranoid subtype (57%), and recent
suicidal behavior or communication (74%), as well as the highest number of
hospitalizations during their illness course and shortest last hospitalization.
CONCLUSION: Suicide risk factors in different treatment phases of schizophrenia
may differ. Substantial numbers of suicide victims with schizophrenia are
receiving inadequate neuroleptic medication, are noncompliant, or do not respond
to adequate typical antipsychotic medication. Adequacy of psychopharmacologic
treatment, particularly in the active illness phase, may be an important factor
in suicide prevention among patients with schizophrenia.
PMID- 10192601
TI - Treatment of patients with functional esophageal symptoms: is there a role for a
psychotherapeutic approach?
PMID- 10192602
TI - The gastroesophageal flap valve.
PMID- 10192603
TI - Endoscopic and surgical integration in the approach to biliary tract disease.
AB - Several techniques are available today to access the bile ducts, all equally safe
and effective. Since 1990, we have studied three groups of patients treated with
different methods: the sequential endoscopic sphincterotomy + laparoscopic
cholecystectomy, the single-stage laparoscopic approach, and the single
laparoscopic-endoscopic approach. The results obtained in 127 patients to date
suggest that one single-stage treatment is more convenient for the patient, while
the combination of endoscopic sphincterotomy with laparoscopic cholecystectomy is
preferable in terms of efficacy and safety.
PMID- 10192604
TI - Treatment of achalasia: recent advances in surgery.
AB - Achalasia is an uncommon motility disorder of the esophagus with an uncertain
etiology. Considerable debate exists regarding the most effective treatment for
long-term relief of symptoms. For decades, pneumatic dilatation has been the
primary treatment option, and surgery was reserved for patients who required
repeated dilations or for those who were not willing to undergo the risk of
perforation associated with dilatation. Recently botulinum toxin injection of the
lower esophageal sphincter has been shown to provide substantial short-term
relief from dysphagia; however, its effect only lasts for a short period of time.
Recently, minimally invasive surgical techniques have been developed to perform a
Heller myotomy effectively with an antireflux procedure. This has become a
primary treatment option for many patients. We present a review of the outcome of
different therapeutic options of achalasia with a special focus on laparoscopic
procedures.
PMID- 10192605
TI - Lactose intolerance: problems in diagnosis and treatment.
AB - Lactose malabsorption and lactase deficiency are chronic organic pathologic
conditions characterized by abdominal pain and distention, flatulence, and the
passage of loose, watery stools. Though malabsorption of the sugar lactose is
determinable by breath hydrogen test or jejunal biopsy, intolerance can only be
confirmed by challenge with lactose-containing food, the response to which may
not be immediate. The difficulty of making a positive diagnosis of these
conditions has led to a proportion of lactose-intolerant patients being
misdiagnosed with irritable bowel syndrome (IBS), which has a remarkably similar
symptom complex and for which there is no current pathophysiologic marker. The
incidence of the two disorders is approximately equal, but the actual proportion
of patients with IBS incorrectly diagnosed in this way varies as a function of
the methodology used. Once correct diagnosis is established, introduction of a
lactose-free dietary regime relieves symptoms in most patients. Symptom
similarity and the resultant incorrect diagnosis of IBS may explain the
refractory nature of some patients labeled as IBS who remain largely unaware of
the relationship between food intake and symptoms.
PMID- 10192606
TI - Standardization in endoscopic reporting: implications for clinical practice and
research.
AB - The large number of endoscopies and endoscopic reports produced in the United
States represents a large repository of clinical data. However, reports are
highly variable in content and structure and therefore cannot be used to create
clinical databases. The introduction of automated endoscopic reporting systems
should permit database creation only if acceptable standards for the structure
and content of the report are developed. The structure of an endoscopic report is
the framework in which the specific details of the endoscopy can be recorded. The
basic components can consist of the following: Patient, Visit, Study, Result,
Diagnosis, and Recommendation. Precise definition of each of these components
requires consensus on what the minimum included elements should be. Experience
with the Minimal Standard Terminology indicates that it is possible to create a
broadly acceptable lexicon of descriptive endoscopic terms which can be included
as a Result. The systematic development of the structure and content of
endoscopic reports is mandatory before it is possible to create large, clinically
useful databases of endoscopic reports.
PMID- 10192607
TI - Prolonged dysphagia after a paraesophageal hernia repair with Nissen
fundoplication.
PMID- 10192609
TI - Endoscopic esophagitis and gastroesophageal flap valve.
AB - The authors studied the relationship of endoscopic esophagitis and
gastroesophageal flap valve (GEFV) in patients with symptomatic gastroesophageal
reflux (GER). On endoscopy, the GEFV was graded as I to IV in 138 patients with
acid regurgitation and heartburn relieved by antacids, and in 54 control subjects
without symptoms suggestive of GER. Grade of GEFV was correlated with the grade
of esophagitis, response to medical treatment, duration of symptoms, obesity,
smoking, sex, and age of the patient. Abnormal GEFV (grades III and IV) was more
frequent in patients with symptomatic GER, both with and without esophagitis,
compared with control subjects (p = 0.000001. p = 0.03). Abnormal GEFV was
significantly more common in patients with GER with esophagitis compared with
those without (p < 0.00001). There was no significant difference in the
distribution of normal and abnormal GEFV in patients with grade I esophagitis.
However, grade 2 and grade 3 esophagitis were associated more commonly with an
abnormal GEFV (p < 0.00001, p < 0.02 respectively). Hiatal hernia is always
associated with an abnormal GEFV. Abnormal GEFV correlated significantly with age
(more frequent when older than 40 years). Sex, duration of symptoms (>3 years),
response to medical therapy, smoking, and obesity (body mass index > 30 kg/m2)
did not correlate significantly with abnormal GEFV. We conclude that endoscopic
esophagitis is usually associated with abnormal GEFV. It is more frequent in
grades 2 and 3 but not grade 1 esophagitis. It is also encountered more commonly
after the age of 40 years.
PMID- 10192608
TI - Antidepressant treatment of patients with diffuse esophageal spasm: a
psychosomatic approach.
AB - The cause of diffuse esophageal spasm (DES) has not been clearly established, and
effective treatment is lacking. To determine whether a psychosomatic approach can
be effective in treating DES patients, nine patients and 26 healthy volunteers
were studied. Esophageal manometry and psychological testing were performed in
both groups. The psychological background of the DES patients was investigated.
Psychiatric diagnoses were made according to the criteria outlined in the
Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, revised. The
authors started psychosomatic treatment with isosorbide dinitrate for 1 month,
then prescribed serotonin reuptake inhibitor antidepressants for an additional
month. Anxiety and depression scores were substantially higher for the DES group
than for the control group. Five of the nine DES patients (56%) were diagnosed as
having major psychiatric disorders. Only one patient showed improvement with
isosorbide dinitrate, and eight patients improved with antidepressants. These
initial observations suggest that psychosomatic treatment with antidepressants
may be effective in the treatment of DES.
PMID- 10192610
TI - Diagnosis of Helicobacter pylori gastritis in children using the 13C urea breath
test.
AB - The clinical recognition of Helicobacter pylori gastritis in children with
recurrent abdominal pain is difficult. We assessed the value of a simplified 13C
urea breath test (13C-UBT) in a selected group of children with nocturnal waking
and disruptive recurrent abdominal pain who fulfilled criteria for endoscopy.
Gastric antral biopsies were examined histologically and by the quick urease test
and were compared with H. pylori serology and the 13C-UBT in a prospective study
of 50 children referred to a tertiary center. Thirty-two patients had gastritis
and of these, 19 had histologically proven H. pylori gastritis. Seventeen of
these 19 patients had a positive 13C-UBT. The sensitivity and specificity of the
13C-UBT compared with the histologic diagnosis of H. pylori was 89 and 90%
respectively. The 13C-UBT was more specific than the H. pylori serology. The 13C
UBT using two breath collections is a reliable and noninvasive diagnostic test
for H. pylori infection in children.
PMID- 10192611
TI - After the eradication of Helicobacter pylori infection, relapse is a serious
problem in Turkey.
AB - Eradication of Helicobacter pylori (Hp) infection is strongly recommended in
duodenal and gastric ulcer. In developed countries the recurrence rate is low;
however, in Turkey, the Hp recurrence rate is suspected to be high as the
prevalence of Hp infection is--as high as 70-80% in the asymptomatic population.
We planned this study to determine the relapse rate of Hp infection after
successful eradication therapy in Turkey. Fifty-two cases including 24 patients
with duodenal ulcer and 28 patients with nonulcer dyspepsia were examined in this
study. The eradication regimen was omeprazole 20 mg twice daily, clarithromycin
500 mg twice daily, and metronidazole 500 mg three times a day for 1 week. All
patients underwent upper gastrointestinal tract endoscopy. At least four samples
from antrum and corpus were taken to enable histologic diagnosis of Hp infection.
After the eradication therapy, endoscopy was repeated at 1, 3, 6, and 12 months,
and Hp-positive patients were dropped from study. With the use of this regimen,
the Hp eradication rate was 92.3% (48/52). After the eradication of Hp infection,
relapse rates were 6.97%, 27.5%, and 11.11% at 3, 6, and 12 months, respectively.
The cumulative relapse rate for 1 year was 41.46%. The results of this study
revealed that after the eradication of Hp infection, recurrence is encountered
very often as a problem in Turkey. We concluded that hygienic and environmental
factors can affect these high relapse rates.
PMID- 10192612
TI - Esophageal manometric and radiologic findings in asymptomatic subjects with
Chagas' disease.
AB - We studied 68 asymptomatic subjects (63 men) aged 19-67 years (median age, 41.5
years), who were candidates to donate blood at the University Hospital of the
School of Medicine of Ribeirao Preto whose serologic examination result for
Chagas' disease was positive. These individuals underwent a resting
electrocardiogram (ECG). chest and esophageal radiographic examinations, and
esophageal manometry. Thirty-three subjects (49%) had normal esophageal and
cardiac examinations. Twenty-eight (41%) had an abnormal ECG and/or abnormal
chest radiograph, 18 of them with normal findings on both esophageal manometry
and radiograph. Two of the other 10 subjects had normal results on manometry and
an abnormal esophageal radiograph. Eight of these subjects had manometric
abnormalities which included decreased contraction amplitude (n = 4), failed
lower esophageal sphincter (LES) relaxation (n = 1), and simultaneous
contractions (n = 3). Esophageal radiographic examination showed no alteration in
five cases and esophageal retention in three. Only seven subjects (10%) exhibited
exclusive esophageal manifestations, that is, simultaneous contractions (n = 5),
simultaneous contractions with failed LES relaxation (n = 1), and esophageal
retention (n = 1). Of the total group of 68 subjects, 17 (25%) had some
esophageal abnormality observed on manometry (14 cases [21%]) and on radiographic
examination (6 cases [9%]). We conclude that asymptomatic subjects with Chagas'
disease may have cardiac and esophageal alterations which may be detectable by
the examinations regularly used to study heart and esophagus.
PMID- 10192614
TI - Long-term cyclosporine for resistant Crohn's disease.
PMID- 10192613
TI - Effect of ursodeoxycholic acid in acute viral hepatitis.
AB - In previously published studies ursodeoxycholic acid (UDCA) showed beneficial
effect on the course of chronic hepatitis. We investigated the effect of UDCA on
the course of acute viral hepatitis in a prospective double-blind study. Seventy
eight consecutive patients were randomly assigned either to the UDCA group or to
placebo. At 12 months of follow-up 76 patients were available for the final
assessment. The analysis of all cases and of the patients with hepatitis B (n =
59) showed a comparable rate of decline of the alanine aminotransferase and other
liver function tests in the treatment group and in the placebo group. However,
the elevation of alanine aminotransferase persisted more frequently in the
placebo group (all cases, p = 0.05; hepatitis B group, p = 0.03). Persistence of
the hepatitis B virus infection, measured by the presence of hepatitis B early
antigen and hepatitis B virus DNA (polymerase chain reaction and hybridization)
at 12 months of follow-up, was observed in I of 33 patients in the UDCA group and
in 6 of 25 patients in the placebo group (p = 0.02). Gallstones detected by entry
ultrasound dissolved in four of eight cases in the UDCA group and in none of six
in the placebo group. We conclude that UDCA has a beneficial effect on the course
of the acute viral hepatitis. It may enhance the clearance of the hepatitis B
virus and thus prevent the development of chronic hepatitis.
PMID- 10192615
TI - Postcolonoscopy appendicitis: a case report.
PMID- 10192616
TI - Gallbladder carcinoma with lymphoid stroma: a case report with
immunohistochemical analyses.
PMID- 10192617
TI - Nonsteroidal anti-inflammatory drugs and gastric mucosal blood flow.
PMID- 10192619
TI - Endosonography in the diagnosis of "blue rubber bleb nevus syndrome": an uncommon
cause of gastrointestinal tract bleeding.
AB - Blue rubber bleb nevus syndrome is a rare condition characterized by the presence
of multiple angiomatic lesions of the skin. These are associated with similar
lesions in other organs, namely in the gastrointestinal tract, causing anemia
through chronic bleeding. We describe the case of a 72-year-old woman with
microcytic anemia. A barium study revealed irregular lacunae in the distal
esophagus. A subsequent endoscopy showed blue nodular lesions similar to angiomas
of the esophagus and stomach fundus. Endosonography confirmed its angiomatic
nature. Exploration of other organs, using magnetic resonance and cranial
computed tomography, did not reveal the presence of this type of lesion. In
physical examination, two angiomatic lesions were observed on the face and lips,
respectively. These were blue in color and compressible, leaving an empty
wrinkled sac that rapidly refilled, typical of angiomas.
PMID- 10192618
TI - Esophageal stricture from idiopathic ulcers in an AIDS patient: a case report and
review of the literature.
PMID- 10192620
TI - Splenosis presenting as an ulcerated gastric mass: endoscopic and endoscopic
ultrasonographic imaging.
AB - A case of an ulcerated gastric wall mass ultimately found to be splenosis is
presented in which the index patient had endoscopic and endoscopic
ultrasonographic evaluation prior to resection. Although no visual features
identified this mass as a splenic implant preoperatively, the lesion appeared to
be atypical for leiomyoma, which led to surgical intervention. The role of
endoscopic ultrasonography in assessing isolated gastric masses is discussed.
PMID- 10192621
TI - A case of fibrosing mediastinitis with obstruction of superior vena cava and
downhill esophageal varices: a rare cause of upper gastrointestinal hemorrhage.
AB - Fibrosing mediastinitis (FM) is an excessive fibrotic reaction that occurs in the
mediastinum and may lead to compression of mediastinal structures (especially
vascular or bronchial). In the present study we describe the first case report of
FM, in a patient who developed downhill esophageal varices and bleeding, which
was secondary to superior vena cava obstruction.
PMID- 10192622
TI - Acute myocardial infarction: a rare presentation of pancreatic carcinoma.
AB - Secondary neoplastic involvement of the heart is common but usually asymptomatic.
Malignancy rarely presents as acute pericarditis, cardiac tamponade, and
myocardial infarction in the same patient. We report a patient with unsuspected
metastatic pancreatic adenocarcinoma who presented with acute pericarditis and
cardiac tamponade and subsequently developed a myocardial infarction due to
coronary artery occlusion secondary to a metastatic deposit around the left
anterior descending artery.
PMID- 10192623
TI - Hepatobiliary dysfunction as the initial manifestation of disseminated
cryptococcosis.
AB - A case of hepatobiliary dysfunction as the initial manifestation of disseminated
cryptococcosis is described. The patient was admitted with symptoms of hepatitis
with cholestatic jaundice. Antibody tests for hepatitis B and C and human
immunodeficiency virus were negative. The patient continued to deteriorate
clinically. Eventually, the patient succumbed to hepatic failure. Autopsy
disclosed systemic cryptococcosis that caused extensive necrosis of the liver. In
review of the literature, only nine cases of cryptococcal infection presenting as
hepatitis, cholangitis, and cholecystitis as initial manifestation were reported.
Four of these patients had been subjected to exploratory laparotomy for clinical
suspicion of acute abdomen. One patient developed cirrhosis as a result of
cryptococcal hepatitis. Two patients succumbed to hepatic failure. Cryptococcosis
is known to occur commonly in immunocompromised patients, yet only two reported
cases presenting as hepatitis were associated with immunocompromised status.
PMID- 10192624
TI - Spontaneous cholecystocutaneous fistula presenting in the gluteal region.
AB - The complication of cholecystocutaneous fistula secondary to calculus
cholelithiasis is an extremely rare occurrence. The incidence has further
decreased with the advent of broad-spectrum antibiotics, ultrasonography, and
safe and early surgical treatment of biliary tract disease. We are reporting a
rare cholecystocutaneous fistula presenting in the right-side gluteal region
below the iliac crest.
PMID- 10192625
TI - Small sigmoid colon cancer with liver metastasis.
PMID- 10192626
TI - Alexander the Great may have died from a perforated peptic ulcer.
PMID- 10192627
TI - Acute appendicitis after barium enema examination.
PMID- 10192628
TI - Spontaneous jejunoileal fistula associated with intestinal strangulation.
PMID- 10192629
TI - 1998 ASHT presidential address. The truth is not negotiable: we can make a
difference. American Society of Hand Therapists.
PMID- 10192630
TI - Reliability of the NK dexterity board.
AB - The NK computerized hand evaluation system includes a dexterity board that can be
used to measure patients' ability to manipulate small, medium, and large objects.
This study evaluated the test-retest reliability of the NK dexterity test. Thirty
seven healthy subjects aged 20 to 54 years completed two occasions of dexterity
testing. Each occasion included bilateral dexterity tests consisting of two
trials of each of three subtests. Intraoccasion intraclass correlation
coefficients (ICCs) indicated fair to excellent reliability (ICC, 0.53-0.86).
Interoccasion ICCs tended to be lower and ranged from 0.39 to 0.83, depending on
the subtest. Reliability tended to be higher with the dominant hand than with the
nondominant hand. Improvements in equipment design and alternative testing
protocols may be needed to ensure consistently excellent reliability in dexterity
scores with this test.
PMID- 10192631
TI - Hand function in workers with hand-arm vibration syndrome.
AB - Hand-arm vibration syndrome has been specially addressed in the Scandinavian
countries in recent years, but the syndrome is still not sufficiently recognized
in many countries. The object of this preliminary study was to describe the
nature and character of vibration-induced impairment in the hands of exposed
workers. Twenty symptomatic male workers (aged 28 to 65 years) subjected to
vibration by hand-held tools were interviewed about subjective symptoms and
activities of daily living and were assessed with a battery of objective tests
for sensibility, dexterity, grip function, and grip strength. The test results
were compared with normative data. The majority of patients complained of cold
intolerance, numbness, pain, sensory impairment, and difficulties in handling
manual tools and in handwriting. The various objective tests showed considerable
variation in indications of pathologic outcome, revealing differences in
sensitivity to detect impaired hand function. Semmes-Weinstein monofilament
testing for perception of light touch-deep pressure sensation, the small-object
shape identification test, and moving two-point discrimination testing for
functional sensibility provided the most indications of pathologic outcomes. The
authors conclude that vibration-exposed patients present considerable impairment
in hand function.
PMID- 10192632
TI - When is a change a genuine change? A clinically meaningful interpretation of grip
strength measurements in healthy and disabled women.
AB - The aim of this study was twofold: 1) to use estimates of random and systematic
error to ascertain the test-retest reliability of grip strength measurements
obtained with the Jamar hand dynamometer in healthy and disabled women, and 2) to
determine the size of the change required to detect a genuine change in grip
strength for accurate and meaningful clinical interpretation. Previous research
has shown grip strength measurements obtained with a Jamar hand dynamometer from
healthy and disabled subjects on different occasions to be reliable. However, the
test-retest reliability has been based on correlation coefficients rather than on
the actual size of the test-retest differences required to detect a genuine
change in grip. The test-retest reliability of maximum grip strength measurements
in 32 healthy women and painfree grip in 10 disabled women with nonspecific
regional pain (NSRP) was determined. Reliability, based on estimates of
systematic and random error, was high in both subject groups. There was no
statistically significant systematic error between tests. Test-retest measurement
error was +/-5.7 kg (12.5 lb) and +/-5.9 kg (13.0 lb) in healthy and disabled
subjects, respectively, 95% of the time. In this population of healthy women and
women with NSRP, any change in grip of less than 6 kg (13.2 lb) could have
occurred by chance. The results of our study suggest that a change of more than 6
kg (13.2 lb) is necessary to detect a genuine change in grip strength 95% of the
time.
PMID- 10192633
TI - Reliability of a patient-rated forearm evaluation questionnaire for patients with
lateral epicondylitis.
AB - PURPOSE: To determine the reliability of a questionnaire designed to assess
forearm pain and function in patients with lateral epicondylitis. METHODS: Forty
seven patients with unilateral lateral epicondylitis completed a patient-related
forearm evaluation questionnaire (PRFEQ) on two occasions. Intraclass correlation
coefficients (ICC 2,1), standard error of measurement (SEM), and 95% confidence
intervals (CIs) were determined for the whole group and for three subgroup
comparisons of male vs. female subjects, subacute vs. chronic lateral
epicondylitis, and work-related vs. non-work-related lateral epicondylitis.
RESULTS: The test-retest reliability for the overall PRFEQ (ICC, 0.89), and its
pain (ICC, 0.89) and function (ICC, 0.83) subscales was excellent. Test-retest
reliability for patients with work-related lateral epicondylitis (ICC, 0.80) was
significantly (p = 0.018) less than for patients with non-work-related lateral
epicondylitis (ICC, 0.94). CONCLUSIONS: The PRFEQ can provide a simple, quick,
and reliable estimate of arm pain and function in patients with lateral
epicondylitis. However, large SEM and 95% CIs limit its ability to accurately
predict individual scores.
PMID- 10192634
TI - Padding and splint fabrication.
PMID- 10192635
TI - Determining the significance of significance: p-values, effect size, and clinical
judgment.
PMID- 10192636
TI - Cerebral amyloid angiopathy in Alzheimer disease is associated with
apolipoprotein E4 and cortical neuron loss.
AB - Pathological correlations were sought between cerebral amyloid angiopathy (CAA)
and other classical neurodegenerative changes in 101 consecutive cases of autopsy
confirmed Alzheimer disease (AD). Some degree of CAA was found in at least one
area of the brain in 81% of the cases; severe CAA was found in at least one brain
region in 29% of the cases. In a subset of 42 cases for which genomic DNA was
available, greater severity of CAA was associated more with cases that were
homozygous for apolipoprotein epsilon4 than in cases with only one or no epsilon4
alleles (Fisher's exact test, p = 0.005). In all brain regions, severity of CAA
was inversely correlated with numbers of neurons. This correlation was
statistically significant in the temporal lobe (r = -0.29,p = 0.004) and the
frontal lobe (r = -0.22, p = 0.02). Our findings suggest that two factors may
modify the severity of AD pathology: Apolipoprotein E4 may accentuate the
vascular deposition of beta-amyloid, and severe CAA may accelerate neuronal loss.
PMID- 10192637
TI - Oligoclonal bands and blood--cerebrospinal-fluid barrier dysfunction in a subset
of patients with Alzheimer disease: comparison with vascular dementia, major
depression, and multiple sclerosis.
AB - As known from inflammatory diseases, oligoclonal bands in the cerebrospinal fluid
(CSF-OCB) may indicate a humoral immune response within the central nervous
system. Previous studies on the CSF IgG content in Alzheimer disease (AD)have
been controversial about the relationship of OCB and elevated IgG indices. To
explore this problem, we combined qualitative (isoelectric focusing) and
quantitative methods (IgG index) to detect intrathecal IgG production and related
these findings to the presence of blood--cerebrospinal-fluid barrier (BCB)
dysfunction. Fifty-one AD patients were compared with patients with vascular
dementia (VD), major depression (MD), multiple sclerosis (MS), and age-matched
control subjects. CSF-OCB could be traced in 20% of AD patients. An elevated IgG
index was found in 6% and a BCB dysfunction in 16% of all AD patients. Either
intrathecal IgG synthesis or BCB dysfunction were detected in a subgroup of 36%
of all AD cases and in 40% of patients with late-onset AD. Intrathecal IgG
synthesis and BCB dysfunction may suggest underlying immunological or
inflammatory changes in an as-yet undefined subgroup of AD patients and support
the notion of a heterogeneous nature of AD.
PMID- 10192638
TI - Methanesulfonyl fluoride (MSF): a double-blind, placebo-controlled study of
safety and efficacy in the treatment of senile dementia of the Alzheimer type.
AB - The purpose of the present study was to evaluate methanesulfonyl fluoride (MSF),
a very long-acting CNS-selective acetylcholinesterase (AChE) inhibitor, as a
palliative treatment for senile dementia of the Alzheimer type (SDAT). In
experiment I, MSF (0.03-0.18 mg/kg) was administered orally to 10 normal
volunteers to measure toxicity and establish dose/response function in
erythrocyte AChE. MSF produced a dose-response function of %inhibition =
(40)(Log10[MSF mg/kg] + 51.7) with no toxicity at these doses. Experiment II was
a 16-week double-blind, placebo-controlled study of the safety and efficacy of
MSF in doses of up to 0.18 mg/kg given three times per week in 5 men and 10 women
(60-82 years), with Mini-Mental State Examination (MMSE) scores of 9-24, who had
SDAT. MSF produced a mean of 89.5% inhibition of erythrocyte AChE in patients and
improved cognitive performance as measured by the MMSE, Alzheimer Disease
Assessment Scale-Cognitive Subscale (ADAS-COG), Global Deterioration Scale, and
the Clinical Interview Based Impression of Change (CIBIC). Most of the
improvement on the ADAS-COG was maintained 8 weeks after ending MSF. No patients
left the study because of drug-related adverse events and there were no toxic
effects. MSF may be a safe and effective palliative treatment for SDAT and
further clinical trials in larger groups of patients are warranted.
PMID- 10192639
TI - Assessing individual patients for cognitive benefits from acetylcholinesterase
inhibitors.
AB - To evaluate an objective method for individually assessing Alzheimer patients for
cognitive benefits from acetylcholinesterase inhibitors, we conducted a secondary
analysis of data from 234 subjects enrolled in a 30-week efficacy trial of
tacrine hydrochloride. We determined which patients showed treatment-related
improvement on the Alzheimer Disease Assessment Scale--Cognitive subscale (ADAS
Cog) and the MiniMental State Examination (MMSE). Four weeks after administration
of the maximum dose, 14% showed significant improvement from baseline in their
ADAS-Cog scores, and 30.6% showed significant improvement in their MMSE scores.
Examination of response patterns over time revealed that 65% of patients showed
no improvement in MMSE scores during the 120-160-mg phases of the trial, whereas
18% showed consistent improvement in MMSE scores during that time. Three percent
of patients showed improvement in their MMSE scores only for the 160-mg
assessment. How the methodology from this study can be generalized to other
Alzheimer patients is discussed. We calculated prediction intervals to document
the magnitude of fluctuation in performance that is normal for Alzheimer patients
similar to those in this study. Patients who change more than the limit specified
by the prediction interval have statistically significantly improved performance.
We determined that an improvement on the MMSE of three or more points across a
time period of 6 weeks marks statistically significant change for an individual.
For intervals between 6 and 16 weeks, improvement of four or more points on the
MMSE is statistically significant. The results indicate that monitoring
individual patients for statistically significant improvements in cognitive
functioning is feasible, sensitive to drug-related changes in performance, and
could facilitate drug monitoring in patients.
PMID- 10192640
TI - Informant-based staging of dementia using the clinical dementia rating.
AB - The staging of dementia is ideally based on both an examination of the patient
and a history taken from an informant. However, in some circumstances, only an
informant history is possible. The aim of this study was to assess the validity
of the Clinical Dementia Rating (CDR) when the rating is based solely on
informant data. The CDR was used in a study of 360 persons aged 78 or older who
were participants in a community survey, the Sydney Older Persons Study. The CDR
was completed in two ways: (1) a social scientist made the ratings based on an
informant interview; and (2) a physician made the ratings after an examination of
the subject. All CDRs were scored in the conventional way, as well as by the
revised method proposed by Gelb and St. Laurent (Alzheimer Dis Assoc Disord
1993;4:202-11). The informant CDR showed moderate agreement with the clinician
CDR, showing that it would be a valid substitute in situations in which the
subject could not be examined. The revised scoring method was slightly easier to
implement than the conventional method.
PMID- 10192641
TI - Sensitivity to semantic cuing: an index of episodic memory dysfunction in early
Alzheimer disease.
AB - Alzheimer disease (AD) is characterized by episodic memory impairment. This study
was aimed at assessing various aspects of episodic memory, and particularly
sensitivity to semantic cuing, in patients with various degrees of cognitive
deterioration, compared with normal elderly subjects. One hundred thirty-one
patients, subdivided into four subgroups as a function of their Mini-Mental State
Examination score, were included. All subjects, including 20 normal elderly
subject, were given an episodic memory test with controlled encoding and
selective reminding. The subgroups of patients were homogeneous in terms of free
recall and recognition, but differed in terms of responsiveness to cuing by
semantic categories corresponding to the to-be-remembered items. The data
confirmed that a severe amnesic syndrome occurs very early in AD, even in a
subgroup of patients who did not meet the criteria for dementia. The data
indicated that free recall performance, characterized in all subgroups by a floor
effect, is not likely to be an appropriate index in pharmacological trials. By
contrast, sensitivity to semantic cuing seemed relatively preserved in the early
stages, and decreased with the progression of the disease. This index would be
the most sensitive index of episodic memory in AD.
PMID- 10192642
TI - History of depression and other psychiatric illness as risk factors for Alzheimer
disease in a twin sample.
AB - Although case-control studies have found elevated risk for Alzheimer disease (AD)
associated with a prior psychiatric history, most of the previous research had
inadequate controls for familial risk factors. Putative psychiatric risk factors
were evaluated for a registry-based sample of 65 twin pairs discordant for AD.
Risk ratios were calculated for psychiatric illness at any time and for episodes
more than 10 years before dementia onset. Prior psychiatric illness was
significantly associated with elevated risk. Most of these cases represented
depressive episodes. When analyses were restricted to individuals whose mental
illness commenced more than 10 years before dementia onset, the magnitude of the
odds ratio decreased markedly. These findings suggest that a history of
psychiatric illness, especially depression, may be associated with an elevated
risk for AD. In particular, these results are consistent with an interpretation
that symptoms of depression and similar complaints represent prodromal phases of
dementia.
PMID- 10192643
TI - Baylor profound mental status examination: a brief staging measure for profoundly
demented Alzheimer disease patients.
AB - There is no brief patient-derived rating scale for staging and following
profoundly demented Alzheimer disease (AD) patients. We developed the Baylor
Profound Mental Status Examination (BPMSE) modeled after the Mini-Mental State
Examination (MMSE) to meet this need. The BPMSE consists of 25 cognitive
questions that assess orientation, language, attention, and motor functioning; 10
examiner ratings of presence or absence of problem behaviors; and 2 qualitative
observations of language and social interaction. Two hundred eight probable or
possible AD patients (MMSE scores of 20 or less) received the BPMSE. Some were
also rated on the clinical dementia rating (CDR) and Lawton activities of daily
living (ADL). A ceiling effect occurred at MMSE scores above 11. BPMSE cognitive
scores and MMSE scores correlated significantly (r = 0.76, p < 0.0001). Subareas
of the BPMSE also intercorrelated significantly. The BPMSE correlated with both
CDR and ADL scores (p < 0.001). Internal consistency, interrater reliability, and
test-retest stability were excellent. There was no floor effect, and BPMSE scores
continued to decline after the MMSE reached 0. The BPMSE is a quick and easy
staging tool with excellent validity and test-retest stability that measures
cognitive function successfully in patients with MMSE scores below 12. The scale
is sensitive to longitudinal change and continues to assess decline when
performance has reached the lowest levels on conventional measures.
PMID- 10192644
TI - Inappropriate sexual behaviors in dementia: a preliminary report.
AB - We investigated types of inappropriate sexual behavior (ISB) and patient
characteristics in geriatric patients with dementia. The study group consisted of
133 consecutive geropsychiatric demented patients admitted to our ward. All
patients underwent standardized diagnostic procedures for dementia, and ISB was
assessed by a questionnaire completed by patients' caregivers and records during
hospitalization. Patients were then subdivided on the basis of the presence or
absence of ISB. Of the 133 demented patients, 20 (15.0%) were reported to
demonstrate ISB at home or during hospitalization. Patients with ISB had various
types of dementia. There were no significant differences in patients with and
without ISB in regard to age, age of onset, gender, educational level, or Mini
Mental State Examination scores. ISB is not unusual in dementia patients and can
be found in different types of dementia. Medical care providers need to be
trained to discuss sexual issues with caregivers and offer ideas and training to
help cope with patients with ISB.
PMID- 10192645
TI - How do we evaluate and utilize data on ethnic differences?
PMID- 10192646
TI - The relationship between lipids/lipoproteins and atherosclerosis in African
Americans and whites: the Atherosclerosis Risk in Communities Study.
AB - PURPOSE: The relationships between lipids/lipoproteins and atherosclerosis were
determined in African Americans and whites to assess the consistency of the
relationship between these two groups. Differences could suggest varying
biological, environmental, or life-style cofactors influencing development of
atherosclerosis. METHODS: In the Atherosclerosis Risk in Communities Study, 2966
African Americans and 9399 whites had determinations of LDL, HDL, HDL2, and HDL3
cholesterol, triglycerides, apolipoprotein A1 and B, and lipoprotein (a). Carotid
intimal-medial thickening (IMT) was measured using B-mode ultrasound imaging.
RESULTS: The associations, using linear regression, between carotid IMT and LDL
cholesterol, HDL cholesterol, and other lipid measurements were significantly
weaker in African Americans than whites. Averaging men and women, a 1.034 mmol/L
(40 mg/dl) difference in LDL cholesterol was associated with a 0.028 mm IMT
difference in whites but a 0.019 difference in African Americans. Similarly, for
HDL cholesterol, a 0.44 mmol/L (17 mg/dl) difference is associated wth 0.026 mm
difference in carotid IMT in whites and 0.011 mm difference in African Americans.
The associations are much weaker in African Americans than whites at the
bifurcation and internal carotid, the carotid sites most prone to
atherosclerosis. Analysis was done stratifying for risk factors that differ
between African Americans and whites, but within most, the relationships remained
substantially weaker in African Americans. CONCLUSIONS: We have observed a
statistically significant difference in the association between many
lipids/lipoproteins and carotid IMT between African Americans and whites.
Analysis of many potential cofactors have not provided an explanation for the
weaker association. Although possible differences in prior levels of these lipids
may provide one explanation for the finding, these results need confirmation in
other studies.
PMID- 10192647
TI - Relationship of serum and dietary magnesium to incident hypertension: the
Atherosclerosis Risk in Communities (ARIC) Study.
AB - PURPOSE: To examine the relationship of serum and dietary magnesium (Mg) with
incident hypertension. The setting was the Atherosclerosis Risk in Communities
(ARIC) Study, which included a biracial cohort, aged 45-64 years, from four U.S.
communities. METHODS: This analysis included 7731 participants (4190 women and
3541 men) free of hypertension at baseline and followed six years. Fasting serum
Mg was measured, and usual dietary intake was assessed with a food frequency
questionnaire. RESULTS: After adjustment for age, race, and a number of other
risk factors, the odds of incident hypertension across ascending quartiles of
serum Mg were 1.0, 0.79, 0.85, and 0.70 in women (p trend = 0.01) and 1.0, 0.87,
0.87, and 0.82 in men (p trend = 0.16). We found no association between dietary
Mg intake and incident hypertension. These associations were attenuated after the
addition of baseline systolic blood pressure to the models. CONCLUSIONS: This
study suggests that low Mg may play a modest role in the development of
hypertension.
PMID- 10192648
TI - High levels of plasma C-reactive protein and future risk of age-related cataract.
AB - PURPOSE: Chronic intraocular inflammation, with or without systemic inflammation,
is associated with increased risk of cataract. Whether systemic inflammation
alone is associated with cataract is unknown. This study examined the association
between plasma C-reactive protein (CRP), a marker of systemic inflammation, and
risk of cataract. METHODS: In the Physicians' Health Study, we recently analyzed
plasma CRP levels in baseline blood specimens from 543 men who later developed
cardiovascular disease, and 543 who did not. These data provided a cost-efficient
means to explore whether baseline plasma CRP is associated with future risk of
age-related cataract. After excluding 252 men with prior diagnosis of cataract or
missing data, we followed the remaining 834 men defined by baseline CRP level for
11 years for incident cataract. We used proportional hazards regression models,
stratified by cardiovascular disease status. RESULTS: Baseline CRP was
significantly higher among men who later developed cataract than levels among
those who remained free of cataract, P = 0.02 (median 1.53 versus 1.23 mg/L). In
a multivariable model adjusted for cardiovascular disease, randomized aspirin and
beta carotene assignments, age, diabetes, cigarette smoking, alcohol consumption,
body mass index, exercise, and parental history of myocardial infarction, the
levels of CRP remained significantly associated with development of cataract (P =
0.001); but the association was less significant in a model using log CRP levels
(P = 0.038). In exploratory analyses of a threshold effect, the excess risk was
significant only among men with levels at or above the 97.5th centile (6.17
mg/L); compared to those with lower levels, the relative risk in these men was
3.00 (95% confidence interval, 1.53 to 5.91; P = 0.002). Relative risks
associated with CRP levels at or above versus below the 85th, 90th, and 95th
percentiles were not significant (relative risks 1.29, 1.50, and 1.77,
respectively). CONCLUSIONS: Overall, our results suggest that elevated levels of
CRP are associated with future risk of cataract in these apparently healthy men.
This early report raises the possibility that systemic inflammation may play a
role in the pathogenesis of age-related cataract.
PMID- 10192649
TI - A prospective study of alcohol consumption and the risk of age-related macular
degeneration.
AB - PURPOSE: Vascular risk factors, including alcohol intake, have been hypothesized
to play a role in the development of age-related macular degeneration (AMD). We
examined the relationship of alcohol intake with AMD in the Physicians' Health
Study (PHS). METHODS: The PHS was a randomized trial of aspirin and beta-carotene
among 22,071 U.S. male physicians age 40 to 84 years at entry. A total of 21,041
physicians with complete data on alcohol consumption and no AMD at baseline were
included in this analysis. Proportional hazards models were used to estimate
relative risks (RR) and 95% confidence interval (CI). RESULTS: During an average
follow-up period of 12.5 years, 278 physicians were confirmed by medical record
review to have incident AMD resulting in vision loss ( acuity 20/30 or worse).
After adjusting for age, randomized treatment assignment, and other potential
risk factors, the RR for > or = 1 drink/week versus < 1 drink/week was 0.97 (CI:
0.78-1.21). For categories of alcohol intake, the RRs for those reporting alcohol
consumption of < 1 drink/week, 1 drink/week, 2-4 drinks/week, 5-6 drinks/week,
and > or = 1 drink/day were 1.00 (referent), 1.00 (0.65-1.55), 0.68 (0.44-1.04),
1.32 (0.89-1.95), and 1.27 (0.93-1.73), respectively. CONCLUSIONS: These
prospective data indicate that alcohol intake is not appreciably associated with
the risk of incident AMD. However, the width of the confidence intervals are
compatible with a possible small effect (reduction or increase) in risk for low
to moderate levels of alcohol intake, which warrant further investigation.
PMID- 10192650
TI - Measurement characteristics of the Women's Health Initiative food frequency
questionnaire.
AB - PURPOSE: The Women's Health Initiative (WHI) is the largest research program ever
initiated in the United States with a focus on diet and health. Therefore, it is
important to understand and document the measurement characteristics of the key
dietary assessment instrument: the WHI food frequency questionnaire (FFQ).
METHODS: Data are from 113 women screened for participation in the WHI in 1995.
We assessed bias and precision of the FFQ by comparing the intake of 30 nutrients
estimated from the FFQ with means from four 24-hour dietary recalls and a 4-day
food record. RESULTS: For most nutrients, means estimated by the FFQ were within
10% of the records or recalls. Precision, defined as the correlation between the
FFQ and the records and recalls, was similar to other FFQs. Energy adjusted
correlation coefficients ranged from 0.2 (vitamin B12) to 0.7 (magnesium) with a
mean of 0.5. The correlation for percentage energy from fat (a key measure in
WHI) was 0.6. Vitamin supplement use was common. For example, almost half of
total vitamin E intake was obtained from supplements. Including supplemental
vitamins and minerals increased micronutrient correlation coefficients, which
ranged from 0.2 (thiamin) to 0.8 (vitamin E) with a mean of 0.6. CONCLUSIONS: The
WHI FFQ produced nutrient estimate, that were similar to those obtained from
short-term dietary recall and recording methods. Comparison of WHI FFQ nutrient
intake measures to independent and unbiased measures, such as doubly labeled
water estimates of energy expenditure, are needed to help address the validity of
the FFQ in this population.
PMID- 10192651
TI - Participation rates in a case-control study: the impact of age, race, and race of
interviewer.
AB - PURPOSE: Despite concerns about declining participation rates in epidemiologic
studies in recent years, relatively few papers have discussed obstacles to
recruiting study participants or strategies for optimizing response rates. This
report describes factors associated with nonparticipation in a population-based,
case-control study of breast cancer and discusses ways to overcome barriers to
participation. METHODS: Contact and cooperation rates were calculated for
participants in the Carolina Breast Cancer Study (CBCS), stratified by case
status, age, race, and race of interviewer. Demographic and breast cancer risk
factor characteristics of partial and full responders also were compared.
RESULTS: Contact rates and cooperation rates varied by case/control status and
demographic characteristics. Contact rates were lower among controls, younger
women, and black women. Cooperation rates were lower among controls, older women,
and black cases. Cooperation rates were higher among both black and nonblack
women when participants and interviewers were concordant on race. CONCLUSIONS:
Obstacles to recruitment seem to differ among race and age subgroups, suggesting
that recruitment strategies may need to be tailored to potential participants
based upon demographic characteristics. Strategies have been implemented to
improve response rates in this and other epidemiologic studies; however,
additional research and innovation in this area are needed.
PMID- 10192652
TI - 1996 Remington lecture: modeling multivariate longitudinal data that are
incomplete.
AB - PURPOSE: We describe the impact that missing data may have on model selection for
longitudinal multivariate data. METHODS: Maximum likelihood was used to fit
several models to ultrasonographic measurements from the Asymptomatic Carotid
Artery Progression Study (ACAPS). Graphical techniques were used to examine
evidence concerning the underlying missing data mechanisms associated with each
model. RESULTS: Using statistical methodology that addressed missing data
substantially increased the statistical efficiency of our analysis of
ultrasonographic data. Only complex models that included segment-specific
parameterizations for longitudinal correlations appeared to allow missing data to
be assumed to occur at random. CONCLUSION: Ignoring the nature of missing data in
conducting statistical analyses can have serious consequences when missingness is
not rare. It may be necessary to fit models of high dimension with maximum
likelihood techniques to address missing data appropriately, however these
approaches may improve statistical efficiency.
PMID- 10192653
TI - Invertebrate compounds acting on the hemostatic mechanism.
AB - Physiological secretions from some invertebrates have toxic effects on mammalian
blood coagulation and fibrinolytic systems. Some of these effects occur because
the substances contained in the secretions resemble the components of the
hemostatic system. Some of the substances have been characterized, and have been
found to have similar molecular weights or sequences, which may indicate a common
ancestry. The components can be divided into five groups: antithrombic agents
(group I); inhibitors and activators of the prothrombinase complex (group II);
substances that affect platelet function (group III); substances that affect the
fibrinolytic mechanism (group IV); and a group of miscellaneous agents whose
activities are difficult to group together (group V). In group I special mention
of the antithrombin agents in Hirudo medicinalis should be made. In group II, the
agents affecting the prothrombinase complex are antistasin from Haementeria
officinalis, ghilanten from Haementeria Ghiliani and the tick anticoagulant
protein from Ornithodoros moubata, a factor V activator/inhibitor from Lonomia
achelous and factor II and factor X activators from L. achelous and Lonomia
obliqua. Examples of factors which affect platelet function (group III) are
glossina from the black fly Glossina morsitans, calin from H. medicinalis,
decorsin (a desintegrin) from Macrobdella decorsa, and FAGA from Stichopus
japonicus selenka. The first three of these are inhibitors of platelet
aggregation, and the last is an inducer. The plasminogen activators (group IV)
from the L. achelous caterpillar and Eutriatoma maculata trigger the fibrinolytic
system, whereas hementin from H. officinalis and hementerin from Haementeria
depressa are directly fibrinolytic. The last group of substances (group V)
include those with factor-XIIa-like activity from D. farinae, kallikrein-like
activity and a factor XIII degrading enzyme from L. achelous, destabilase from H.
medicinalis and prolixin S (nitroforin 2, or anti-factor-IXa) from Rhodnius
prolixus. Some of these components have been well characterized, cloned and
prepared in recombinant form, and seem to be very promising from the therapeutic
point of view.
PMID- 10192654
TI - Contribution of a new, rapid, quantitative and automated method for D-dimer
measurement to exclude deep vein thrombosis in symptomatic outpatients.
AB - Ninety-nine consecutive outpatients with symptoms suggestive of deep vein
thrombosis (DVT) were tested for the presence of D-dimer using a new, rapid
method (BC D-Dimer) based on the agglutination principle and performed on a BCT
analyzer. Dimertest Gold EIA and VIDAS D-Dimer devices were used as comparative
methods. Venography was performed in all patients, with DVT diagnosed in 39 of
them (34 proximal). The BC D-Dimer test proved to be rapid, automated and well
suited for individual tests with a good reproducibility (coefficient of variation
% 1.5-5.3). Its performance was comparable with that of the other methods, as
indicated by the areas under the receiver operating characteristic curves (Gold
EIA 0.95; VIDAS 0.95; BC D-Dimer 0.91) and the coefficients of correlation
(Pearson's coefficients from 0.832 to 0.876). On the basis of the Kappa
coefficients, there was quite a good concordance between the three tests. At the
cut-off levels that provided the highest sensitivity (97.4%, for all the tests),
the negative predictive values were similar for all methods, at over 95%. The
corresponding specificity ranged from 62.7 to 81.7%. In conclusion, this study
shows that the new method can be included in prospective clinical trials to test
the utility of D-dimer measurement in combination with other non-invasive
diagnostic procedures in the management of the diagnosis of DVT.
PMID- 10192655
TI - Hereditary deficiency of vitamin-K-dependent coagulation factors in Rambouillet
sheep.
AB - A flock of Rambouillet sheep experienced unexpected lamb mortality associated
with excessive bleeding at the time of parturition. Most lambs died of blood loss
through the umbilicus or into subcutaneous tissues. Subsequently, nine ewes which
had previously delivered lambs that bled to death were bred to the suspected sire
of the previous bleeding lambs. Fifteen lambs were born alive the following
Spring, and three males and one female bled clinically. These lambs had markedly
decreased factor IX (< 16%) and factor X (< 4%) activities, with variably
decreased factor II (11-36%) and factor VII (20-37%) activities. Protein C
chromogenic activity was also markedly decreased (< 1%) in these lambs. The
results from crossed immunoelectrophoresis and 'protein-induced-in-vitamin-K
absence' determination of the plasma of affected lambs, with antiserum directed
against coagulation factor X, protein C or proteins S, suggested that these
proteins were not carboxylated normally. Examination of liver from one lamb in
the first batch and the four subsequent lambs did not reveal a known vitamin K
antagonist. The breeding data suggested that the coagulopathy in these sheep was
inherited as an autosomal recessive trait. The genetic or molecular defect that
exists in these lambs is unknown, but possibilities include abnormal gamma
glutamyl carboxylase activity or abnormal metabolism of vitamin K.
PMID- 10192656
TI - The effects of oestrogen replacement therapy on haemostatic variables in
postmenopausal women with non-insulin-dependent diabetes mellitus.
AB - Women with diabetes mellitus have an increased risk of developing coronary heart
disease which may be related at least partially to unfavourable changes in
haemostasis. The effect of oestrogen replacement therapy on haemostasis has not
been studied systematically in women with non-insulin-dependent diabetes mellitus
(NIDDM) and therefore this study was performed for that purpose. Twenty-five
postmenopausal women with NIDDM were treated with 2 mg of 17-beta-oestradiol
orally for 3 months in a double-blind, crossover, placebo-controlled trial.
During the last 16 days of active treatment, 1 mg of norethisterone acetate was
added for 10 days for endometrial protection. Blood samples were taken at
baseline and after 68 days of active or placebo treatment. Treatment with
oestradiol was followed by a marked decrease in the activity of plasminogen
activator inhibitor, compared with placebo. The activity of tissue plasminogen
activator increased significantly. Levels of antithrombin decreased during
treatment with oestradiol, whereas no changes were seen in levels of fibrinogen,
von Willebrand factor, prothrombin fragment 1+2, protein S, protein C or
resistance to activated protein C. In conclusion, oestrogen replacement therapy
in postmenopausal women with NIDDM improved the fibrinolytic activity, while only
clinically insignificant alterations in the clotting system were seen. These
changes in haemostasis may have a favourable impact on the risk for coronary
heart disease in diabetic women.
PMID- 10192657
TI - Soluble, thrombin-related material in arterial thrombi and plasma studied during
catheter-directed intra-arterial thrombolysis.
AB - We investigated soluble, thrombin-related material in arterial thrombi and venous
plasma during catheter-directed thrombolysis with alteplase. Arteriography was
performed before thrombolysis and 0.5, 3, 10 and 24 h after the onset of
treatment in six patients with (sub)acute lower extremity ischaemia caused by
native artery or bypass occlusion. Samples were collected simultaneously from the
thrombus and venous blood. After adding inhibitors of thrombin and plasmin, the
centrifuged samples were assayed for prothrombin fragment 1+2 (F1+2), thrombin
antithrombin complex (TAT) and fibrinopeptide A (FPA). Levels of F1+2, TAT and
FPA were extremely elevated in the thrombus-related samples before the blood flow
was re-established (at 0 and 0.5 h) in all five successfully treated patients. In
comparison, venous plasma levels of F1+2, TAT and FPA were moderately elevated,
and reached a maximum at 3 h. In conclusion, material aspirated from lysing human
thrombi formed in vivo contains large amounts of F1+2, TAT and FPA, but our
methods prevented us from detecting enzymatically active thrombin.
PMID- 10192658
TI - Fibrinogens Bern IV, Bern V and Milano XI: three dysfunctional variants with
amino acid substitutions in the thrombin cleavage site of the Aalpha-chain.
AB - Thrombin-induced cleavage of fibrinopeptide A is the initial step in the
conversion of fibrinogen to fibrin. Three dysfunctional fibrinogen variants are
described with an amino acid substitution at position 16 of the Aalpha-chain: the
fibrinogen variants Bern IV and Milano XI having an Arg-->His substitution and
the variant Bern V having an Arg-->Cys substitution. Routine coagulation studies
revealed prolonged plasma thrombin and reptilase clotting times in all patients,
and a discrepancy between the plasma levels of fibrinogen determined by the
clotting assay and electroimmunoassay. The defect was localized by high
performance liquid chromatography analysis of fibrinopeptide release and
confirmed by polymerase chain reaction and sequencing of exon 2 of the Aalpha
chain. Immunoblotting analysis with a rabbit antiserum against human serum
albumin indicated that albumin was linked to the additional sulfhydryl group of
fibrinogen Bern V. The assay of tissue-plasminogen-activator-induced plasmic
degradation revealed that the fibrinolysis of fibrin Bern V was delayed, whereas
fibrin Bern IV was digested in the same way as normal fibrin.
PMID- 10192659
TI - No evidence for an increased risk of venous thrombosis in patients with factor V
Leiden by the homozygous 677 C to T mutation in the methylenetetrahydrofolate
reductase gene.
AB - Hyperhomocysteinemia is an established risk factor for arterial and venous
thrombosis. Recently, it has been shown that a C to T mutation at nt position 677
in the methylenetetrahydrofolate-reductase (MTHFR) gene is a common cause of
moderately elevated levels of plasma homocysteine in adults. In order to
investigate whether the newly recognized genetic alteration in the MTHFR gene
potentiates the thrombotic tendency in patients with factor V Leiden, we studied
81 unrelated patients with a history of venous thrombosis and a heterozygous
factor V Leiden mutation. In addition, we analyzed 111 family members of 34
families in which the proband had a heterozygous factor V Leiden mutation. In all
individuals, factor V Leiden and the MTHFR mutation were tested and the
occurrence of venous thrombotic events was evaluated retrospectively. Seventy
seven healthy subjects without the factor V Leiden mutation or any other known
thrombotic risk factor served as a control group. The prevalence of the
homozygous MTHFR mutation was similar in index patients (10 of 81, 12%) and in
the control group (10 of 77, 13%). The median age at first thrombosis in index
patients was 32 years (range 22-69 years) in 10 patients with heterozygous factor
V Leiden and T/T MTHFR mutation, and 34 years (range 6-72 years) in 71 patients
with the factor V Leiden mutation only. In the family members, the prevalence of
thrombosis was not higher in patients with factor V Leiden and +/+ MTHFR genotype
than in those with only the heterozygous factor V Leiden mutation. We conclude
from these data that the 677 C to T mutation in the MTHFR gene does not represent
a significant additional risk factor for venous thrombosis in patients with
factor V Leiden mutation.
PMID- 10192660
TI - Thrombosis in a patient with combined homozygosity for the factor V Leiden
mutation and a mutation in the 3'-untranslated region of the prothrombin gene.
AB - The factor V Leiden mutation and a guanine-to-adenine mutation at nucleotide
20210 in the 3'-untranslated region of the prothrombin gene are the most
prevalent genetic defects in patients with deep venous thrombosis. Heterozygosity
for the factor V Leiden and the prothrombin gene mutations is found in
approximately 20 and 6% of unselected patients with deep venous thrombosis,
respectively, whereas the prevalences of the two mutations in the general
Caucasian population are approximately 6 and 2%, respectively. We evaluated an 18
year-old man presenting with a spontaneous episode of superficial venous
thrombosis for the presence of an inherited thrombotic disorder. After excluding
deficiencies of antithrombin, protein C, and protein S, genomic DNA from the
patient was tested for the presence of the factor V Leiden and prothrombin gene
mutations. Consanguinity was not present in the family. Genotyping demonstrated
that the patient was homozygous for the factor V Leiden and prothrombin gene
mutations. The likelihood of identifying an individual in the general population
who is homozygous for both mutations similar to our patient is estimated to be
less than 1 in 10 million.
PMID- 10192661
TI - Incidence of G20210A mutation in severe vaso-occlusive events complicating sickle
cell anemia.
PMID- 10192662
TI - Haemostatic factors and risk of coronary heart disease.
PMID- 10192663
TI - Total and free levels of tissue factor pathway inhibitor: a risk factor in
patients with factor V Leiden?
PMID- 10192664
TI - A match made in heaven? Quality-related activities and quality research.
PMID- 10192665
TI - Strategies for reducing the pain and discomfort of nasogastric intubation.
PMID- 10192666
TI - A randomized, clinical trial comparing butylcyanoacrylate with octylcyanoacrylate
in the management of selected pediatric facial lacerations.
AB - OBJECTIVE: To compare two tissue adhesives, butylcyanoacrylate and
octylcyanoacrylate, in the treatment of small (<4 cm) superficial linear
traumatic facial lacerations in children. METHODS: This was a randomized,
clinical trial with parallel design. 94 children <18 years of age seen in the ED
of a tertiary care pediatric hospital with a facial laceration suitable for
tissue adhesive closure underwent laceration closure using either
butylcyanoacrylate or octylcyanoacrylate. The primary outcome was the cosmetic
result at three months rated from photographs by a plastic surgeon on a visual
analog scale (VAS). Secondary outcomes included the time to perform the
procedure, the perceived difficulty of the procedure, the pain perceived by the
patient, and a wound evaluation score at ten to 14 days and three months.
RESULTS: Ninety-four patients were randomized with 47 in each group. The two
groups were similar for baseline demographic and clinical characteristics. There
was no difference in the three-month cosmesis VAS (median, 70.0 mm for n-butyl-2
cyanoacrylate vs 67.5 mm for octylcyanocrylate, p = 0.84). There was no
difference between the groups for time to complete the procedure (p = 0.88),
parent/patient-perceived pain of the procedure (p = 0.37), or physician-perceived
difficulty of the procedure (p = 0.33). Similarly, there was no difference
between the groups for the percentage of early (p = 0.58) or late (p = 0.71)
optimal wound evaluation scores. CONCLUSIONS: In the closure of small linear
pediatric facial lacerations, octylcyanoacrylate is similar to butylcyanoacrylate
in ease of use and early and late cosmetic outcomes. The superior physical
properties of octylcyanoacrylate appear to add little benefit to the management
of these selected lacerations. Physician preference and differing costs may
dictate use for these small selected lacerations.
PMID- 10192667
TI - Patient satisfaction with an emergency department asthma observation unit.
AB - OBJECTIVE: To compare levels of patient satisfaction between the diagnostic and
treatment protocols in an ED-based asthma observation unit (AOU) and those with
standard inpatient hospitalization. METHODS: This was a prospective, randomized,
controlled trial with a sample of 163 patients presenting to the ED with acute
asthma exacerbations over a 30-month period. Eligible patients were those who
could not resolve their symptoms after three hours of standard ED therapy.
Patients were then randomly assigned to an ED-based AOU (experimental group) or
to customary inpatient care (control group). Patient satisfaction and problems
with care processes were assessed by standardized instrumentation at discharge in
both groups. RESULTS: The AOU patients scored higher than those randomized to the
inpatient hospitalization protocol on four summary ratings of patient
satisfaction measures: received service wanted, recommendation of the service to
others, satisfaction with the service, and overall satisfaction. The AOU patients
reported fewer total number of problems with care received, and fewer specific
problems with communication, emotional support, physical comfort, and special
needs, than did the inpatient group. However, the AOU patients reported more
problems regarding their knowledge of financial costs and liabilities for their
service than did the inpatients. CONCLUSION: Patients were more satisfied and had
fewer problems with rapid diagnosis and treatment in the AOU than they did with
routine inpatient hospitalization. Since AOUs represent a new ambulatory service
modality, patients would benefit from greater awareness of the costs and coverage
for AOUs as compared with hospital inpatient care. These findings have important
implications for the future short- and long-term success and feasibility of ED
based AOUs.
PMID- 10192668
TI - Comparison of topical anesthetics and vasoconstrictors vs lubricants prior to
nasogastric intubation: a randomized, controlled trial.
AB - OBJECTIVE: To determine whether pre-treatment of the nose and throat with topical
anesthetics and vasoconstrictors would reduce the pain associated with
nasogastric (NG) intubation. METHODS: This was a prospective, randomized,
controlled trial assessing the pain of NG intubation in patients pretreated with
topical anesthetics and vasoconstrictors vs surgical lubricants alone. The
subjects were 40 alert, cooperative adult patients requiring NG intubation
without allergies to the study medications or contraindications to their use from
a suburban university-based ED. The patients in the experimental group had
phenylephrine 0.5% sprayed in their noses followed by instillation of 5 mL of 2%
lidocaine jelly. Their throats were sprayed with 2% tetracaine and 14%
benzocaine. The control patients received intranasal lubrication only. The
primary outcome measured was pain of NG intubation on a 100-mm visual analog
scale. Other outcomes included nasal pain, discomfort from gagging, and the
incidences of vomiting, choking, and epistaxis. RESULTS: The mean age (+/-SD) was
54.8+/-22.3 years; 20 (50%) were female. The patients who had a combination of
topical anesthetics and vasoconstrictors inserted prior to NG intubation
experienced significantly less overall pain/ discomfort than did the control
patients [28.6 mm (95% CI = 17.3 to 39.9 mm) vs 57.5 mm (95% CI = 44.9 to 70.1
mm), p = 0.001]. The patients in the experimental group also experienced
significantly less nasal pain than did the patients in the control group [18.1 mm
(95% CI = 8.0 to 28.2 mm) vs 44.4 mm (95% CI = 30.4 to 58.6 mm), p = 0.003] and
significantly less discomfort from gagging than the patients receiving
pretreatment with a lubricant alone [24.1 mm (95% CI = 11.1 to 37.1 mm) vs 50.9
mm (95% CI = 36.7 to 65.1 mm), p = 0.006]. There was no between-group difference
in the frequencies of adverse effects. CONCLUSIONS: Use of topical lidocaine and
phenylephrine for the nose and tetracaine with benzocaine spray for the throat
prior to NG intubation results in significantly less pain and discomfort than use
of a nasal surgical lubricant alone. Widespread use of topical anesthetics and
vasoconstrictors prior to NG intubation is recommended.
PMID- 10192669
TI - The effect of a quality improvement program on paramedic on-scene times for
patients with penetrating trauma.
AB - OBJECTIVE: To decrease paramedic on-scene times (OSTs) for major trauma patients
through a focused quality improvement (QI) program. METHODS: A prospective study
was conducted from 1993 through 1997 to determine the impact of a QI program on
paramedic OSTs. All penetrating trauma patients transported by paramedics to Los
Angeles County/USC Medical Center, a Level-1 trauma center, were included, and
all cases with OSTs > 20 minutes were reviewed in detail for extenuating
circumstances. Cases including multiple victims or unsecured scenes were
considered "acceptable deviations." All others were considered "fallouts," which
prompted extensive review with the paramedics and their field supervisors.
RESULTS: Prior to the inception of the QI project there was a 4.1% fallout rate
of penetrating trauma patients with OSTs > 20 minutes. This fallout rate fell to
1.5% in 1997 (p < 0.01). Mortality rates among these fallouts decreased from 5.1%
to 0.8% during the study period (p < 0.01). CONCLUSIONS: An intensive QI program
can have a significant, positive impact on paramedic OSTs among patients with
penetrating trauma.
PMID- 10192670
TI - Retrospective review of emergency department patients with non-variceal upper
gastrointestinal hemorrhage for potential outpatient management.
AB - OBJECTIVE: To determine the number of ED patients with non-variceal upper
gastrointestinal hemorrhage (NVUGIH) who could have been managed as outpatients
through application of previously developed clinical guidelines. METHOD:
Descriptive study based on retrospective chart review of patients who presented
with acute upper gastrointestinal hemorrhage (UGIH) to the ED of an urban
teaching hospital from July 1 to December 31, 1996. Applying the clinical
guidelines published by a health maintenance organization (HMO) group (no high
risk endoscopic features/varices/portal hypertensive gastropathy, no
debilitation, no orthostatic vital sign change, no severe liver disease, no
serious concomitant disease, no anticoagulation or coagulopathy, no fresh,
voluminous hematemesis or multiple episodes of melena on the day of presentation,
no severe anemia, and adequate home support), patients who could have been
managed as outpatients after esophagogastroduodenoscopy (EGD) were identified and
analyzed. RESULTS: 145 UGIH patients were seen in the ED, of whom 128 (88%) were
admitted and 111 (77%) underwent EGD. 21 (19%) had varices, leaving 90 (81%) with
NVUGIH. 18 of these 90 patients (20%, 95% CI = 12% to 28%) fulfilled guidelines
for outpatient management and had the following characteristics with p < 0.05:
younger age [mean 54.2+/-5.5 (SEM) vs 63.8+/-1.9 years], less transfusion (0.9+/
0.3 vs 3.7+/-0.4 units), and shorter length of stay (2.1+/-0.4 vs 5.3+/-0.7
days). None of the 18 outpatient management patients had any complications.
CONCLUSION: In a non-HMO urban teaching hospital, 18 patients with NVUGIH met
criteria for outpatient management in a six-month period and none developed a
complication during a mean in-hospital stay of 2.1 days.
PMID- 10192671
TI - Concert medicine: spectrum of medical problems encountered at 405 major concerts.
AB - OBJECTIVES: To identify factors predictive of patient load at major commercial
concert first-aid stations, and to characterize the spectrum of presenting
injuries and illnesses at such events. METHODS: This study was a retrospective
case series of patients presenting to on-site first-aid stations at five major
concert venues in southern California over a five-year period. The authors
compared the number of patients per ten thousand attendees (PPTT) with four
potential predictors (music type, overall attendance, temperature, and indoor vs
outdoor location) using univariate techniques and negative binomial regression.
The spectrum of chief complaints observed is described. RESULTS: There were 1,492
total patients out of 4,638,099 total attendees at 405 separate concerts. The
median patient load per concert was 2.1 PPTT, ranging from 0 PPTT at 53 concerts
to 71 PPTT at a punk rock festival that turned into a riot. Patient load varied
significantly by music category (p = 0.0001) but not with overall attendance,
temperature, or indoor vs outdoor location. Median PPTT by music category ranged
from 1.3 PPTT for rhythm and blues to 12.6 PPTT for gospel/Christian, with
negative binomial regression indicating that rock concerts had 2.5 times (95% CI
= 2.0 to 3.0) the overall patient load of non-rock concerts. Music type, however,
was able to account for only 4% of the variability observed in the regression
model. Trauma-related complaints predominated overall, with similar rates at rock
and non-rock concerts. Four cardiac arrests occurred at classical concerts.
CONCLUSION: Rock concert first-aid stations evaluated 2.5 times the patient load
of non-rock concerts overall, although there was substantial concert-to-concert
variability. Trauma-related complaints predominate at both rock and non-rock
events. These data may assist individuals and organizations planning support for
such events.
PMID- 10192672
TI - Blood lead levels in emergency department patients with retained lead bullets and
shrapnel.
AB - OBJECTIVE: To determine whether patients with retained lead shrapnel who present
to the ED have elevated whole blood lead levels (BLLs) compared with matched
control patients. METHODS: Test subjects were patients with x-ray evidence of
retained lead shrapnel who presented to any of three urban EDs, and consented to
inclusion in the study. BLLs were obtained from 15 ED patients, and data
regarding time since injury and symptoms of plumbism were collected. Control
subjects consisted of 15 ED patients, without similar lead exposure, matched for
age, sex, race, and place of dwelling as determined by zip code, who also
presented to any of the same three EDs. RESULTS: The mean (+/-SD) BLL in the test
subjects was 17+/-9.78 microg/dL (range 7-50 microg/dL). Time since impalement
ranged from 1 to 45 years. The mean BLL in the control subjects was 7+/-3.77
microg/dL (0-16 microg/dL). This difference was statistically significant (two
tailed t-test p = 0.002). CONCLUSIONS: In this preliminary study, the patients
with retained lead shrapnel who presented to the ED had significantly elevated
BLLs, compared with the matched control subjects. Chronic plumbism may be
considered in patients with retained lead shrapnel, and a history should be taken
to assess the presence of symptoms referable to plumbism. These patients may
require long-term follow-up to assess the development of elevated blood lead
level and lead toxicity.
PMID- 10192673
TI - Home observation for asymptomatic coin ingestion: acceptance and outcomes. The
New York State Poison Control Center Coin Ingestion Study Group.
AB - OBJECTIVES: To obtain preliminary estimates of the acceptance rate and the
frequency of adverse outcomes, and to identify issues related to acceptance,
associated with management of asymptomatic pediatric coin ingestion by home
observation, in preparation for a large-scale prospective study. METHODS:
Scripted telephone follow-up of callers who had reported asymptomatic pediatric
coin ingestions to one of five poison control centers six to 36 months
previously, which had been managed by home observation. RESULTS: Of the 67
callers enrolled, 41 (67%) reported contacting a physician regarding the coin
ingestion, despite home observation instruction by poison control center
personnel. Those who did not recall being instructed in home observation were
more likely to have contacted a physician than those who did. Nearly all,
however, were satisfied with the advice they had been given. One child developed
subsequent symptoms; as per the instructions that had been given by poison
control center personnel, his parent sought physician evaluation, revealing an
esophageal coin, which was removed uneventfully. No other child developed
complications. CONCLUSIONS: Although all of the 67 children managed by home
observation did well, most of their caretakers had not accepted this management
strategy. Acceptance, while unrelated to satisfaction, may be related to
comprehension of the instructions caregivers are given. A prospective study of
home observation for asymptomatic pediatric coin ingestion would be safe and
would allow further examination of factors affecting acceptance.
PMID- 10192674
TI - Time delays in accessing stroke care in the emergency department.
AB - OBJECTIVE: To delineate components of delay within the hospital ED for patients
presenting with symptoms of stroke. METHODS: A prospective registry of patients
presenting to the ED with signs or symptoms of stroke was established at a
university hospital from July 1995 to March 1996. The ED arrival time, time to
being seen by an emergency physician (EP), time to CT scan, and time to neurology
consultation were obtained by medical record review. RESULTS: The median delay
(interquartile range) from ED arrival to being seen by an EP for the 170 eligible
subjects was 0.42 (0.20-0.75) hours. The median delay to CT scan was 1.88 hours
(1.25-2.67) and the median delay to neurology consultation was 2.42 hours (1.50
3.48). Age, race, sex, and hospital discharge diagnosis had little influence on
delay. Subjects arriving by emergency medical services (EMS) had a significantly
shorter time to being seen by an EP (0.33 vs 0.50 hours) when compared with those
who arrived by other means. Time to CT scan was shorter by 0.5 hours for patients
arriving by EMS as well. These differences persisted when stratified by out-of
hospital delay times. CONCLUSIONS: These data suggest that arriving by EMS is
associated with shorter times to being seen by an EP and receiving a CT scan. The
influence of EMS on delays associated with rapid medical care of stroke patients
reaches beyond the out-of-hospital transport phase.
PMID- 10192675
TI - Feasibility of an emergency department-based tuberculosis counseling and
screening program.
AB - OBJECTIVE: To assess the feasibility and effectiveness of an ED-based
tuberculosis (TB) screening program. METHODS: A TB screening program of adult ED
patients was conducted at a university hospital ED with 46,000 annual visits that
serves a poor urban community. Patients were screened on weekdays during business
hours. ED patients were counseled about the disease and the screening procedure
and, after consent, purified protein derivative (PPD) tests were placed. Patients
returned in 48-72 hours for reaction reading and post-test counseling. PPD
positive patients received a physical examination, chest x-ray, and HIV testing
and were referred to a city TB clinic for possible treatment. RESULTS: Overall,
873 patients were counseled, 630 were eligible for screening, and 374 (59.4%)
consented to PPD testing. Of the 203 (54.1%) who returned, 32 (15.8%) were PPD
positive. No active case was detected, but 26 patients were referred to the
health department. Eighteen kept their appointments and all 13 who were started
on therapy completed treatment. Targeted screening of groups aged 55 years or
more, nonwhite groups, and those with other high-risk factors would detect 84% of
PPD-positive cases while testing only 48% of eligible patients. CONCLUSION: An ED
based TB screening program is feasible and can identify many patients requiring
treatment. Targeted screening of high-risk groups could reduce the program cost,
but would miss some cases.
PMID- 10192676
TI - Disturbing trends: the epidemiology of pediatric emergency medical services use.
AB - OBJECTIVE: To compare pediatric ambulance patients transported for chief
complaints of suicide, assault, alcohol, and drug intoxication (SAAD) with
pediatric patients transported for all other chief complaints. METHODS: An out-of
hospital database for the primary transporting service in an urban area was
analyzed for patients 0-20 years of age from 1992 to 1995. Chief complaints by
age, gender, and billing status were analyzed. RESULTS: There were 17,722
transports. The SAAD group comprised 14.9% of all transports (suicide attempt
1.6%, assault 5.9%, alcohol intoxication 3.2%, and drug abuse 4.2%). The
proportion of transports due to SAAD increased with age: 0-11-year-olds (4.2%);
11-16-year-olds (17.5%); and 17-20-year-olds (20.3%) (p = 0.0001). Genders were
equally represented in the overall group, while males comprised 52.6% of the SAAD
transports (p = 0.032). In the SAAD group, the majority of transports for
assaults (55.9%) and alcohol (58.8%) involved males, while females were the
majority in transports for suicide (52.3%) and drug abuse (66%) (p = 0.0001).
Reimbursement sources differed, with those in the SAAD group less likely to be
reimbursed by private or public (Medicaid, government) insurance (p < 0.0001)
compared with the overall group. CONCLUSIONS: A substantial proportion of
pediatric emergency medical services transports are for high-risk conditions.
This patient population differs from the overall group by age distribution and
reimbursement source.
PMID- 10192677
TI - Metabolic acidosis in restraint-associated cardiac arrest: a case series.
AB - The mechanism of death in patients struggling against restraints remains a topic
of debate. This article presents a series of five patients with restraint
associated cardiac arrest and profound metabolic acidosis. The lowest recorded pH
was 6.25; this patient and three others died despite aggressive resuscitation.
The survivor's pH was 6.46; this patient subsequently made a good recovery.
Struggling against restraints may produce a lactic acidosis. Stimulant drugs such
as cocaine may promote further metabolic acidosis and impair normal behavioral
regulatory responses. Restrictive positioning of combative patients may impede
appropriate respiratory compensation for this acidemia. Public safety personnel
and emergency providers must be aware of the life threat to combative patients
and be careful with restraint techniques. Further investigation of sedative
agents and buffering therapy for this select patient group is suggested.
PMID- 10192678
TI - Statistical methodology: IX. survival analysis.
AB - Survival analysis is a group of statistical methods used to analyze data
representing the time to an event of interest, e.g., the duration of survival
after an out-of-hospital cardiac arrest or the length of time a patient stays in
the ED. Survival analysis properly accounts for patients who are lost to follow
up and for patients who have not yet experienced the event of interest at the end
of the study's observation period (censored data). This article acquaints the
reader with the terminology, methodology, and limitations of survival analysis.
Specific methods discussed include life tables, the Kaplan-Meier product limit
estimate, the log-rank test, and the multivariate Cox proportional hazards model.
PMID- 10192679
TI - BB or not foreign-body BB?
PMID- 10192680
TI - Internet-based prescribing and dispensing trouble medical and pharmacy boards.
PMID- 10192681
TI - Key findings of evidence-based reports announced.
PMID- 10192682
TI - Subpotent vaccine lot recalled, recommendations on supplemental doses issued.
PMID- 10192683
TI - 1997 saw HMO membership up, hospital days down.
PMID- 10192684
TI - Benchmarking the allocation of pharmacists' time.
PMID- 10192685
TI - Coenzyme Q10.
PMID- 10192686
TI - Medicine is changing--so are the bugs.
PMID- 10192687
TI - The changing face of nosocomial candidemia: epidemiology, resistance, and drug
therapy.
AB - The changing epidemiology and therapy of nosocomial candidemia are discussed. The
frequency of nosocomial bloodstream infections by Candida species has risen
dramatically in the past two decades. The arrival of antifungal drugs with better
tolerability than conventional amphotericin B has resulted in widespread use of
systemic antifungal therapy. With the introduction of new systemic antifungals,
however, there have been major shifts in the epidemiology of candidal bloodstream
infections toward species with less susceptibility to the available antifungal
agents. Reports of in situ antifungal resistance are also becoming more common.
Strategies for preventing the emergence of resistance have been suggested but
have not undergone clinical trials. Antifungal susceptibility testing is becoming
an increasingly important tool in the management of nosocomial candidemia.
Treatments that have been undergoing investigation for use in these infections
include combination therapies, lipid-based amphotericin B formulations, cytokines
as adjuvant therapy, and novel antifungal agents such as voriconazole, SCH56592,
and echinocandins. New antifungals in development may offer enhanced activity
against pathogenic Candida species with less toxicity than amphotericin B.
Antifungal susceptibility testing will play a major role in determining the
treatment of resistant infections.
PMID- 10192688
TI - Therapeutic interchange of conjugated and esterified estrogens in a managed care
organization.
AB - A program designed to curb increases in drug costs in an HMO by substituting
esterified for conjugated estrogens was developed and studied. Patients were
voluntarily switched from conjugated to esterified estrogens at an HMO in
Washington State. Women were informed about the conversion through newsletters
and during clinic and pharmacy visits and received physician and pharmacist
counseling. Cost savings were estimated, and patient acceptance was evaluated by
interviewing women in four groups, including women who were switched from
conjugated to esterified estrogens and then switched back (C-E-C group), women
who were not switched (C-C group), and women who were switched to esterified
estrogens and not switched back (C-E group). During the first six months, 14,601
(89.2%) of 16,364 women taking conjugated estrogens were switched to esterified
estrogens; of these, 13,654 (93.5%) continued taking esterified estrogens for at
least six months. The HMO avoided $653,119 of an expected $750,000 cost increase
for oral estrogen therapy during the first year of the program. A total of 754
women were interviewed; 65.8% in the C-E-C group and 78.4% in the C-E group
reported being satisfied with the information they received. The conversion
experience was rated as positive by 28.3% of women in the C-E-C group and 41.5%
of women in the C-E group, negative by 25.1%, and 8.9%, and neutral by 46.6% and
49.6%. An HMO avoided a large increase in drug costs by substituting esterified
for conjugated estrogens; only 6.5% of patients were switched back to conjugated
estrogens at their physicians' or their own request; most patients thought the
conversion was a neutral or positive experience.
PMID- 10192689
TI - Safety of insulin lispro: pooled data from clinical trials.
AB - The safety of insulin lispro was compared with that of regular human insulin of
recombinant DNA origin (Humulin R, Lilly), with special emphasis on the
development and progression of the chronic complications of diabetes mellitus in
relation to insulin therapy. Ten clinical trials of 3634 patients with type 1 and
type 2 diabetes mellitus were analyzed. The primary focus was treatment-emergent
adverse events, and the secondary focus was the development and progression of
the chronic complications of diabetes. The evaluations were based on pertinent
laboratory values, predetermined disease-specific COSTART (coding symbol and
thesaurus for adverse event terminology) terms, physician evaluations of
patients, and physical examinations. There were no clinically or statistically
significant differences in the frequency of treatment-emergent adverse events or
progression of retinopathy, neuropathy, or cardiovascular disease reported with
each therapy. There was no difference between insulin lispro and Humulin R in the
occurrence and progression of kidney disease as measured by changes in serum
creatinine levels. Pooled data from clinical studies show that insulin lispro has
a safety profile comparable to that of Humulin R.
PMID- 10192690
TI - Stability of fumagillin in an extemporaneously prepared ophthalmic solution.
AB - The stability of fumagillin 70 microg/mL (as the bicyclohexylammonium crystal) in
an extemporaneously prepared ophthalmic solution was studied. An ophthalmic
solution of fumagillin 70 microg/mL was prepared by combining 120 mg of
fumagillin bicyclohexylammonium crystals with 20 mL of 0.9% Sodium Chloride
Injection, USP, and 20 mL of an ophthalmic irrigating solution. The solution was
stored in 12 sterile semi-opaque dropper bottles; 4 bottles were stored at 25
degrees C exposed to light, 4 were stored at 25 degrees C in the dark, and 4 were
stored at 4 degrees C in the dark. Samples were taken on days 0, 7, 14, 21, and
28 and analyzed by high-performance liquid chromatography. Sterility was tested
as well. In the solutions stored at 25 degrees C, 17-30% of the initial drug
concentration was lost during the first week. The solution protected from light
and stored at 4 degrees C lost about 12% of active drug by week 4. There was no
change in color or odor in any of the solutions and only a minor change in pH
over the study period. There was no evidence of microbial growth in any of the
solutions tested. Fumagillin 70 microg/mL (as the bicyclohexylammonium crystal)
in 0.9% sodium chloride injection and an ophthalmic irrigating solution
containing benzalkonium chloride was stable in the dark for 14 days at 4 degrees
C.
PMID- 10192691
TI - Cost analysis of remifentanil and fentanyl for neurosurgical anesthesia.
PMID- 10192692
TI - Long-term heavy use of diphenhydramine without anticholinergic delirium.
PMID- 10192693
TI - Establishing realistic performance standards for community pharmacists' drug-use
review activities in managed care contracts.
PMID- 10192694
TI - Redefining the practice of military pharmacy.
PMID- 10192695
TI - Intravenous clonidine for hypertensive emergencies.
PMID- 10192696
TI - Splitting bupropion extended-release tablets.
PMID- 10192697
TI - The pharmacist as a healer.
PMID- 10192698
TI - Current literature.
PMID- 10192699
TI - Microglial and astrocytic change in brains of Creutzfeldt-Jakob disease: an
immunocytochemical and quantitative study.
AB - AIM: The relationship between microglial cells and astrocytes in brains from
patients with Creutzfeldt-Jakob disease (CJD) was immunohistochemically and
quantitatively studied. MATERIALS AND METHODS: CJD cases, including three with
subacute spongiform encephalopathy (SSE), three with panencephalopathic type of
CJD (PECJD) and six normal controls were examined. Microglial cells were
preferentially labeled by monoclonal anti-KP1 (CD68) antibody and astrocytes by
polyclonal anti-glial fibrillary acidic protein (GFAP) antibody. Two cytokines
were labeled by polyclonal anti-tumor necrosis factor-alpha (TNF-alpha) and
polyclonal interleukin-1alpha (IL1alpha). RESULTS: In the CJD brains, microglial
cell density was significantly higher in the white matter than in the cerebral
cortex. In contrast, astrocyte density was significantly higher in the cortex
than in the white matter. In the PECJD cases, many hypertrophic microglial cells
were clustered along the margin of the demyelinated white matter whereas severely
demyelinated white matter contained few microglial cells. The microglial cells
were also located in vacuoles in myelinated fibers of the internal capsule in the
PECJD cases, which resembled myelinopathic alteration in vacuolar myelopathy. The
GFAP-positive astrocytes proliferated much more numerously in the severely
demyelinated white matter. The densities of astrocytes and microglial cells
showed a significantly negative correlation in the cerebral cortex. The density
of the white matter microglia did not differ between the PECJD and SSE cases. TNF
alpha and IL1alpha were expressed by microglial cells, but the TNF-alpha-positive
microglial cells were very few in both SSE and PECJD cases. A subset of IL1alpha
positive microglia was found in the SSE case white matter, although the number of
KP 1-positive microglial cells greatly surpassed the number of IL1alpha-positive
ones. CONCLUSION: These results imply that microglia are increased in number
before demyelination and become hypertrophic while phagocytosing myelin in PECJD,
and that the negative correlation between the density of microglia and astrocytes
is not regulated by either cytokine.
PMID- 10192700
TI - Evaluation of malignant features in oligodendroglial tumors.
AB - BACKGROUND: Oligodendroglial tumors present us with some unsolved problems with
reference to the pathological diagnosis of the malignancy, the classification,
and the biological behavior. PATIENTS AND METHODS: We investigated 60 surgical
specimens from 47 patients. This series contained 17 oligodendrogliomas, 4 oligo
astrocytomas, 32 anaplastic oligodendrogliomas, and 7 anaplastic oligo
astrocytomas. The simple five parameters, which are high cellularity, nuclear
atypia, mitotic index, necrosis, and endothelial proliferation, were
microscopically observed and we designated the sum of the positive parameters as
the "histological score of malignancy" to express the histopathological degree of
malignancy. RESULTS AND CONCLUSIONS: The mean values of the "histological score
of malignancy" and mean MIB 1 staining indices demonstrated significantly higher
values in high-grade oligodendroglial tumors than in low-grade tumors. In
contrast, mean p53 staining indices did not show statistically significant
differences between the low-grade and high-grade tumors. The findings of
"gliofibrillary oligodendrocyte" on GFAP (glial fibrillary acidic protein)
immunostain and of "chicken wire pattern" of tumor vessels on HE stain were
observed significantly more frequently in high-grade oligodendroglial tumors. The
malignant grade of the astrocytic components in the mixed oligoastrocytomas
appeared to be correlated well with that of the oligodendroglial components. In
the 12 recurrent cases, malignant transformations at the second surgery occurred
in 5 of 6 patients whose diagnosis at the first surgery was a low-grade
oligodendroglial tumor, with a mean interval of 111 months. Accordingly, the
malignant transformations are not infrequent and require considerably long
intervals in the oligodendroglial tumors.
PMID- 10192701
TI - Immunocytochemical detection of insulin-like growth factor II (IGF-II) in choroid
plexus papilloma: a possible marker for differential diagnosis.
AB - BACKGROUND: Insulin-like growth factor II (IGF-II) has been detected in the
choroid plexus of animals by means of immunohistochemistry and in situ
hybridization, and this factor is thought to play an important role in the
central nervous system (CNS). Little is known, however, about the presence and
localization of this substance in the choroid plexus and in choroid plexus
papilloma in humans. MATERIALS AND METHODS: 5 normal choroid plexus and 10
choroid plexus papillomas were examined for IGF-II by immunocytochemistry. IGF-II
was not detected in normal human choroid plexus, whereas it was found in choroid
plexus papilloma. Furthermore, to assess the possibility that IGF-II could serve
as an immunohistological marker of choroid plexus papilloma, we used the same
technique to examine paraffin-embedded samples from various kinds of brain
tumors. RESULTS AND CONCLUSION: Our results suggest that IGF-II may be a useful
marker for choroid plexus papilloma in differential diagnosis.
PMID- 10192702
TI - Primary melanocytoma arising from the thoracic leptomeninges case.
AB - Primary melanocytoma arising from the leptomeninges of the spinal cord is very
rare. A surgical specimen of a thoracic meningeal tumor was resected from a 75
year-old woman complaining of gait disturbance was investigated. Magnetic
resonance imaging and myelography showed a dumb-bell-type tumor in the subdural
space at the 1st to 2nd thoracic vertebrae. The tumor was subtotally resected
because of adhesion to the lamina and thoracic medulla. The localized, gelatinous
black tumor showed a well-defined margin without dissemination or infiltration.
The tumor had a thin capsule and was composed of solid proliferation of
neoplastic melanocytes. Neither whorl formation nor foci of palisaded nuclei were
observed. The neoplastic cells were of two major types: an epithelioid- or
polygonal-shaped type and a spindle-shaped type, and had a large nucleus, a
prominent nucleolus, coarse chromatin, and melanin-pigments in their cytoplasm.
Only a few mitotic figures were observed. They were positive for HMB-45 and S-100
protein. This case was considered to be primary melanocytoma arising from the
thoracic leptomeninges.
PMID- 10192703
TI - Cervical myelopathy in mucopolysaccharidosis type IV.
AB - We describe our experience with 8 Italian patients having mucopolysaccharidosis
type IV, diagnosed between 1 and 10 years of life, who presented odontoid
hypoplasia causing cervical myelopathy. We discuss the possibility of cranio
cervical stabilization in order to reduce the neurological complications.
PMID- 10192704
TI - Cerebral B-cell lymphoma following treatment for Tolosa-Hunt syndrome.
AB - We herein report a unique case of cerebral lymphoma which occurred after
lymphocytic neuritis of cranial nerves causing Tolosa-Hunt syndrome and
demonstrate the histological difference between these two diseases. A 70-year-old
woman developed a sensory disturbance in the first and third divisions of the
left trigeminal nerve and a left ocular movement disturbance five years before
death. Although she was clinically diagnosed to have a schwannoma in the left
cavernous sinus, a histologic examination verified a diffuse infiltration of T
lymphocytes in the left trigeminal ganglion. Corticosteroid therapy was
effective. Thereafter she demonstrated a disturbance of consciousness and
dysphasia four years after surgery. A T1-weighted magnetic resonance image (MRI)
disclosed high intensity lesions in both the basal ganglia and corpus callosum.
She also showed progressive spastic paralysis. At autopsy a diagnosis of primary
intracranial B-cell lymphoma was made. Although there was no invasion of the
lymphoma cells into the left trigeminal nerves, a mild inflammatory infiltration
of T cells still remained.
PMID- 10192705
TI - Infiltrating extradural spinal angiolipoma.
AB - BACKGROUND: Angiolipomas are considered to be rare. They are benign mesenchymal
tumors generally located in the subcutaneous tissue of trunk and limbs. METHODS:
The authors report a thoracic epidural angiolipoma mimicking a vertebro-epidural
metastasis. The patient suffered from medullary compression related to an
extradural mass in T6. RESULTS: Pathological ex-, amination was obtained from
tumoral samples. They consisted of mature adipose tissue with numerous sections
of abnormal vascular channels. CONCLUSIONS: Reviewing literature particular
attention is paid to some questions raised in connection with different kinds of
vertebro-epidural tumors. The authors give importance to relationships between
angiolipomas and angiomyolipomas using MRI as a tool in differential diagnosis.
Pathogenesis is evokated especially regarding the role of corticotherapy, the
case herein reported lying within this therapeutical context.
PMID- 10192706
TI - Brain dysgenesis in Cornelia de Lange syndrome.
AB - The neuropathological findings in a neonatal case of Cornelia de Lange syndrome
(CDLS) were described. Two different types of lesions were revealed in the
affected brain. The first type was classified as perinatal hypoxic-ischemic brain
damage, associated with cyanotic congenital heart anomalies: subarachnoideal,
intraventricular, and parenchymal hemorrhage, and multiple necrosis in the
cerebral white matter, basal ganglia, internal capsule, thalamus, mammillary
bodies and dentate nucleus. This type may be non-specific and common in premature
babies dying soon after birth. On the other hand, the second type was classified
as congenital dysgenesis of the brain: microbrachycephaly, immature or simple
convolution pattern of the cerebral gyri, thickened leptomeninges, persistent
subpial granule cells, hypoplasia of the anterior thalamic nuclei,
neurohypophysis, lateral geniculate body, cerebral peduncle, ventral pons and
cerebellar internal granular layer, and heterotopic cell nests in the cerebellar
white matter. This type may indicate that the maturation of the brain can be
disturbed in the fetal period, particularly in the mid-gestational period. In
conclusion, pathognomonic or specific changes of CDLS might be absent in the
brain. However, congenital dysgenesis of the brain, especially that found in the
diencephalon and the cortico-ponto-cerebellar system, may constitute morphologic
evidence explaining the severe growth retardation and neurological abnormalities
in CDLS.
PMID- 10192707
TI - Corticobasal degeneration with hippocampal involvement.
PMID- 10192708
TI - Yersiniosis I: microbiological and clinicoepidemiological aspects of plague and
non-plague Yersinia infections.
PMID- 10192709
TI - Effect of adding clofazimine to combined clarithromycin-ethambutol therapy for
Mycobacterium avium complex septicemia in AIDS patients.
AB - This study compared the efficacies of clarithromycin-ethambutol and
clarithromycin-ethambutol-clofazimine for the treatment of Mycobacterium avium
complex (MAC) in AIDS patients. Thirty-four patients were randomized into two
groups to receive clarithromycin 2 g/day and ethambutol 20 mg/kg/day, with or
without clofazimine 200 mg/day. The evaluation was based primarily on blood
cultures becoming negative after 2 months of therapy, but survival at 12 months
and clinical evolution were also assessed. Inclusions were prematurely stopped
because of a communication reporting increased mortality associated with
clofazimine. At 2 months, the blood cultures of 55% of the clarithromycin
ethambutol group patients versus 81% of the clarithromycin-ethambutol-clofazimine
group were negative; this difference is not significant (P=0.42). Only one
relapse was observed during the study. No clarithromycin-resistant strain was
isolated. No apparent difference in either survival or clinical evolution was
observed in this small number of patients (median survival, 144 days in the
clarithromycin-ethambutol group and 236 days in the clarithromycin-ethambutol
clofazimine group, P=0.44). The clarithromycin-ethambutol combination appears to
be an effective and well-tolerated first-line therapy against MAC infections in
AIDS patients.
PMID- 10192710
TI - Randomised study of the possible adjuvant effect of BCG vaccine on the
immunogenicity of diphtheria-tetanus-acellular pertussis vaccine in Senegalese
infants.
AB - Following a study in Senegal (1990-1995) in which the relative efficacy of a
diphtheria-tetanus-acellular pertussis vaccine (DTaP) was compared with that of a
diphtheria-tetanus-whole-cell pertussis vaccine in children given a simultaneous
injection of Bacille Calmette-Guerin (BCG) vaccine, this subsequent study was
conducted to evaluate the possible adjuvant effect of the BCG vaccine on
acellular pertussis vaccine components. A second objective was to compare the
immunogenicity of these components when administered in accordance with a 2-4-6
month (spaced) schedule or an accelerated 2-3-4-month schedule. In all, 390
healthy Senegalese infants were randomly divided into three groups of 130
infants. Antibodies to acellular pertussis components were measured in serum
samples obtained within 2 days of the first DTaP dose and 1 month after the third
dose. BCG vaccine, given simultaneously with the DTaP vaccine, did not influence
the immunogenicity of the acellular pertussis vaccine components when compared
with separate administration of the two vaccines. Infants immunised according to
a 2-4-6-month schedule had a significantly higher immune response than those
immunised according to a 2-3-4-month schedule with respect to the response to
pertussis toxoid assessed by seroneutralisation on Chinese hamster ovary cells
(P<0.0001). These results suggest that BCG and DTaP vaccines can be given
simultaneously without interference or enhancement and that more optimal
immunogenicity is achieved with an extended than with an accelerated schedule.
PMID- 10192711
TI - Use of the polymerase chain reaction for rapid detection of high-level mupirocin
resistance in staphylococci.
AB - The minimum inhibitory concentrations (MICs) of mupirocin were determined by the
E test (AB Biodisk, Sweden) and the agar dilution method for 107 staphylococci.
The organisms consisted of 34 coagulase-negative staphylococci and 73 methicillin
resistant Staphylococcus aureus. Polymerase chain reaction (PCR) primers designed
to amplify a 456 bp region of the plasmid-borne isoleucyl tRNA synthetase gene
(ileS-2), responsible for high-level mupirocin resistance in staphylococci, were
used on DNA preparations from these isolates. Isolates with high-level mupirocin
resistance due to the ileS-2 gene should be PCR positive. There was close
correlation between the E test and agar dilution MIC values, with only two
strains differing by more than two serial dilutions. Most (51 of 54 strains) of
the high-level resistant strains (MIC>256 microg/ml) were resistant to the
highest concentration of mupirocin tested (1024 microg/ml). PCR correctly
classified all but four (96%) of the isolates in accordance with the results of
agar dilution. All four isolates that gave discrepant results were methicillin
resistant Staphylococcus aureus. Two of these were PCR positive, yet the MIC of
mupirocin for these strains was <0.06 microg/ml; on prolonged incubation they
produced halos within the inhibition zone on agar diffusion testing, suggesting
that the phenotypic results may have been erroneous. One of 54 isolates for which
the MIC exceeded 256 microg/ml was PCR negative when tested by the original
methodology, but a 456 bp product was produced when retested using a lowered
annealing temperature. One isolate for which the MIC of mupirocin was 16
microg/ml by agar dilution and 8 microg/ml by the E test was positive by PCR. PCR
of the ileS-2 gene is a useful, rapid method for detecting high-level mupirocin
resistance in staphylococci.
PMID- 10192712
TI - Laboratory implementation of the polymerase chain reaction for confirmation of
pulmonary tuberculosis.
AB - Decision analysis methods were used to compare four mycobacteriology laboratory
strategies with respect to time to confirmation and exclusion of smear-positive
and smear-negative cases of pulmonary tuberculosis. Strategies assessed included
the following: (i) polymerase chain reaction (PCR) on all respiratory specimens;
(ii) PCR on smear-positive specimens and on the broth of vials for other
specimens attaining a growth index >10 in a radiometric culture detection system;
(iii) PCR on smear-positive specimens only; and (iv) radiometric culture
detection, with DNA probe for species identification of vials attaining a growth
index >999. Strategies i and ii had predicted average times to confirm cases of 5
and 7.6 days, respectively, and remained within 3 days of each other over a broad
range of PCR performance with smear-negative specimens. In contrast, case
confirmation times using strategies iii and iv were 10.4 and 15.3 days,
respectively. Only 10% of specimens were processed by PCR in strategy ii. Times
to confirm smear-negative cases were comparable for strategies i and ii when PCR
sensitivity was <40% with these specimens. Times to exclude pulmonary
tuberculosis were similar for all strategies. Given the current suboptimal
performance of PCR with smear-negative specimens, strategy ii offers accelerated
case confirmation with limited PCR usage.
PMID- 10192713
TI - A four-year review of fatal Aspergillosis.
AB - To investigate the incidence, underlying diseases, and macropathological and
microbiological features of invasive aspergillosis in a university hospital, the
protocols of 1187 autopsies performed during the 4-year period 1993-1996 were
reviewed. Invasive aspergillosis was diagnosed as the cause of death in 48 (4%)
cases, four (8%) of which did not involve severe primary immunosuppression. In
seven (15%) cases no pulmonary involvement was found; in six of these cases the
portal of infection could not be established, whereas in one case invasive
aspergillosis originated from Aspergillus peritonitis. Aspergillus grew in 42% of
the samples obtained from the respiratory tracts of 32 patients with pulmonary
aspergillosis and submitted within 10 days antemortem; at least one positive
culture was obtained from 20 (63%) of these patients. It is concluded that the
diagnosis of aspergillosis by means of culture has an appreciable sensitivity.
Fatal invasive aspergillosis was rare among patients without severe
immunosuppression, whereas invasive aspergillosis without pulmonary involvement
was unexpectedly frequent.
PMID- 10192714
TI - Comparative activity of eighteen antimicrobial agents against anaerobic bacteria
isolated in South Africa.
AB - The in vitro activity of 18 antimicrobial agents was determined against 378
anaerobic bacteria isolated in Bloemfontein, South Africa, during 1996/97.
Against the gram-positive isolates, MICs of penicillin and cefoxitin were >0.5
microg/ml and >16 microg/ml, respectively, for five and three strains of non
perfringens Clostridium spp. Seventeen Peptostreptococcus anaerobius strains were
resistant to penicillin (MIC > or = 2 microg/ml). All gram-positive anaerobes
tested except one Peptostreptococcus sp. and one Clostridium sp. were susceptible
to dalfopristin-quinupristin (MICs < or = 1 microg/ml). The carbapenems exhibited
excellent activity against the gram-positive isolates and were effective against
most gram-negative anaerobes, with the exception of the fusobacteria. Only seven
strains exhibited decreased susceptibility to trovafloxacin (MICs > 2 microg/ml).
In mixed anaerobic/aerobic infections, carbapenems and the fourth-generation
quinolone trovafloxacin were the agents most suitable for us as broad-spectrum
monotherapy.
PMID- 10192715
TI - Detection of Candida mannoproteinemia in patients with neutropenic enterocolitis.
AB - To assess the role of Candida spp. in the etiology of neutropenic enterocolitis
complicating aggressive cytotoxic chemotherapy, a dot immunobinding assay for an
immunodominant Candida mannoprotein antigen was employed in 20 patients with
hematologic malignancies. Candida antigen was detected in at least one serum
sample from 12 (60%) patients. Eleven (92%) patients were cured when an
antifungal agent was added to the antibacterial treatment. In eight patients a
selective anticandidal therapy with fluconazole was administered on the basis of
positive Candida mannoproteinemia, and treatment was successful in all cases but
one. Detection of Candida mannoproteinemia seems to be a useful diagnostic tool
in patients with neutropenic enterocolitis and represents an additional tool for
selecting a less empiric, low toxic antifungal treatment with fluconazole.
PMID- 10192716
TI - Susceptibility of Candida species isolated from female prostitutes with
vulvovaginitis to antifungal agents and boric acid.
AB - The aim of this study was to determine the antifungal susceptibility of 108
Candida albicans and 23 Candida glabrata isolates obtained from female
prostitutes with vulvovaginitis, a population for which available data is
limited. Amphotericin B, flucytosine, and fluconazole were tested by broth
microdilution, and boric acid was tested by the agar dilution method. The
susceptibility patterns found in this population were the same as those in the
general population. Candida glabrata required greater concentrations of boric
acid for inhibition in vitro than did Candida albicans.
PMID- 10192717
TI - Diagnosis and follow-up of Whipple's disease by amplification of the 16S rRNA
gene of Tropheryma whippelii.
AB - Amplification of the 16S rRNA gene of Tropheryma whippelii was performed in eight
patients with Whipple's disease and 34 control patients to confirm a diagnosis of
Whipple's disease and to monitor the course of disease. Polymerase chain reaction
(PCR) tests were positive before treatment in 13 of 15 tissue samples from
Whipple's disease patients (gut 8/8; lymph nodes 2/2; bone marrow 1/2; peripheral
blood 2/3), in contrast to none of 54 tissue samples from controls. PCR tests
converted to negative within 4-6 months in six of the Whipple's disease patients
undergoing therapy. These results show that PCR is a reliable and useful tool for
diagnosis of Whipple's disease and for monitoring bacterial elimination during
antibiotic therapy.
PMID- 10192718
TI - Significance of cytoplasmic staining in the cytomegalovirus pp65 antigen test.
AB - Immunostaining of the cytomegalovirus (CMV) pp65 antigen in the nucleus of
peripheral blood leukocytes is a highly specific tool for diagnosis of active CMV
infection. In the present study, the significance of cytoplasmic staining of
leukocytes, observed in some patients with active CMV disease, was investigated.
The ring-like appearance of cells with stained cytoplasm was shown to be
nonspecific and inducible by incubation of blood leukocytes with interferon-gamma
in vitro. Thus, only nuclear staining should be considered diagnostic in the CMV
pp65 antigen test.
PMID- 10192719
TI - Isolation of Alloiococcus otitidis from the external ear in children.
PMID- 10192720
TI - Clarithromycin-induced acute psychoses in peptic ulcer disease.
PMID- 10192722
TI - Evaluation of antral biopsies used in the rapid urease test for Helicobacter
pylori culture.
PMID- 10192721
TI - Unusual case of Aeromonas sobria cellulitis associated with the use of leeches.
PMID- 10192723
TI - Human T-cell leukemia/lymphoma virus type II infection in Spain. HTLV Spanish
Study Group.
PMID- 10192724
TI - Evaluation of xylose-galactosidase medium, a new plate for the isolation of
Salmonella, Shigella, Yersinia and Aeromonas species.
PMID- 10192725
TI - A case of Guillain-Barre syndrome due to infection with Rickettsia conorii.
PMID- 10192726
TI - A sentinel node biopsy in breast cancer patients.
PMID- 10192727
TI - Characteristics and prognostic factors in patients with differentiated thyroid
cancer who underwent a total or subtotal thyroidectomy: surgical approach for
high-risk patients.
AB - Differentiated thyroid cancer grows slowly in general. But some patients repeat
recurrence and progress finally to death. To clarify the difference of their
prognosis and establish the appropriate thyroid surgery, we studied 105 patients
with differentiated thyroid cancer who were treated with total or subtotal
thyroidectomy, excluding those with small tumors, under uniform conditions
regarding thyroidectomy. There were 77 women and 28 men aged 19 to 76 years (mean
54.7 years). More than 60% (alive) were followed up for longer than 10 years.
Thirty-eight (36%) patients had recurrences. There were 19 deaths. Twelve of 31
patients with locoregional recurrence died and 7 of these 12 died of locoregional
control failure (neck and mediastinum). Age at first operation, tumor size, and
local tumor extension increased the rate of recurrence significantly.
Multivariate analysis confirmed that age, locoregional recurrence, and distant
metastasis significantly affected survival. Although lymph node metastases were
not a prognostic factor, for patients at high risk for recurrence who are older,
and have large tumors with invasion, complete resection of cervical lymph nodes
is advised to prevent local recurrence and prolong the disease-free interval.
Prolongation of the disease-free interval may lead to prolonged survival time.
PMID- 10192728
TI - Apoptosis and proliferative activity in thyroid tumors.
AB - To clarify the growth mechanisms of thyroid tumors, we examined apoptotic cells
in 61 thyroid tumors, consisting of 14 adenomas, 35 papillary carcinomas, 4
follicular carcinomas, and 8 undifferentiated carcinomas, using terminal
deoxynucleotidyl transferase mediated deoxyuridine triphosphate digoxigenin-nick
end labeling (TUNEL). The proliferative activity was also evaluated
immunohistochemically using the monoclonal antibody to Ki-67 antigen (MIB-1) in
the same tumors. The apoptotic index (AI) was expressed as a percentage of the
TUNEL-positive cells in the tumor cells, and a proliferation index (PI), being
the percentage of Ki-67 positive cells, was calculated for each tumor. The
overall level of AI was very low in all histotypes of the thyroid tumors
analyzed, the mean AI being 0.5 +/- 0.4 in adenoma, 0.4 +/- 0.3 in differentiated
carcinoma, and 1.8 +/- 1.5 in undifferentiated carcinoma. The PI in the thyroid
tumor subtypes was significantly lower in adenoma and differentiated carcinoma,
at 0.5 +/- 0.7 and 1.1 +/- 0.7, respectively, than that in undifferentiated
carcinoma at 14.5 +/- 3.7 (P < 0.05). There was no correlation between
clinicopathological factors and AI or PI in differentiated thyroid carcinoma. Our
findings suggest that apoptosis occurs infrequently in thyroid tumors, and that
proliferative activity markedly differs according to the thyroid tumor subtypes.
Moreover, the ratio between proliferating cells and apoptotic cells may reflect
thyroid tumor progression.
PMID- 10192729
TI - The long-term results of upper dorsal sympathetic ganglionectomy and endoscopic
thoracic sympathectomy for palmar hyperhidrosis.
AB - To assess and compare the long-term results of upper dorsal sympathetic
ganglionectomy (UDS) and endoscopic thoracic sympathectomy (ETS), we examined 84
patients who underwent UDS and 71 patients who underwent ETS for the treatment of
palmar hyperhidrosis. The period of follow-up ranged from 37 to 228 months. The
immediate success rate was 100% in the UDS group and 98.6% in the ETS group.
Troublesome compensatory hyperhidrosis occurred in 67.8% of the UDS patients and
84.8% of the ETS patients; however, 55% of the UDS patients and 63% of the ETS
patients felt satisfied with their operation. The main reasons for
dissatisfaction were recurrence and compensatory hyperhidrosis. Interestingly,
simultaneous cure of plantar hyperhidrosis occurred in 28 (40%) of the UDS
patients and 28 (44%) of the ETS patients with concomitant plantar hyperhidrosis.
ETS required both a shorter operation time and hospital stay than UDS. Thus, we
now perform ETS as the treatment of choice because of its excellent illumination
and adequate magnification via a minimally invasive approach. The use of ETS as
the first choice of treatment for palmar hyperhidrosis is supported not only by
the immediate results, complications, and cure of plantar hyperhidrosis, but also
by the long-term results. Nevertheless, compensatory hyperhidrosis was also a
major complication after ETS.
PMID- 10192730
TI - Complications associated with enteral nutrition using catheter jejunostomy after
esophagectomy.
AB - The present study was conducted on 78 patients, encountered over a 7-year period,
who had a catheter-feeding jejunostomy placed at the time of thoracoabdominal
esophagectomy for esophageal cancer. A broad-based attachment of the jejunal wall
to the peritoneum at the place of entry of the catheter was used. Enteral
nutrition was begun an average of 10 days after the operation, the caloric
content was increased gradually, and the mean duration was 69 days. There were
three patients who suffered from local skin erosion at the site of catheter
entry, and seven who developed diarrhea and/or a feeling of abdominal fullness,
but none of the patients showed any signs of peritonitis or ileus. The morbidity
rates related to enteral nutrients and placement of the catheter jejunostomy were
8.9% and 3.8%, respectively. These findings demonstrate that a broad-based
attachment of the jejunal wall to the peritoneum at the place of entry of the
catheter is useful for preventing leakage or twisting of the jejunum, and for
reducing the incidence and severity of the complications of catheter jejunostomy
feeding.
PMID- 10192731
TI - Estimation of Physiologic Ability and Surgical Stress (E-PASS) as a new
prediction scoring system for postoperative morbidity and mortality following
elective gastrointestinal surgery.
AB - Overwhelming surgical stress exceeding a patient's reserve capacity causes a
disruption of homeostasis, leading to various postoperative complications. This
study was undertaken to develop a new scoring system, "E-PASS", standing for the
Estimation of Physiologic Ability and Surgical Stress, that predicts the
postsurgical risk by quantification of the patient's reserve and surgical stress.
E-PASS comprises the preoperative risk score (PRS), the surgical stress score
(SSS), and the comprehensive risk score (CRS) that is determined by both scores.
These scores were computed by a multiple regression analysis conducted on 292
consecutive patients who underwent elective common gastrointestinal operations at
one hospital between 1992 and 1995 (internal group). The usefulness of the scores
was evaluated in 989 consecutive patients who underwent the same surgical
procedures during the same period at another hospital (external group). The
morbidity and mortality rates increased similarly in both groups as the CRS
increased. A marked step-up of both rates was observed at a CRS > 1.0, reaching
mortality rates of 20% in the internal subjects and 28.5% in the external
subjects. These results suggest that the E-PASS scoring system is reproducible,
and that it may be useful for surgical decision making. This system requires no
special examinations and can be used in every hospital.
PMID- 10192732
TI - Clinicopathologic variables affecting survival of distal colorectal cancer
patients with macroscopic invasion into the adjacent organs.
AB - A total of 506 distal colorectal cancer patients were classified into two groups,
to clarify the variables affecting survival of the patients with macroscopic
invasion into the adjacent organs: 47 cases showed invasion (invasive group)
while the other did not show invasion (noninvasive group). Differences between
the invasive and noninvasive groups were found in eight variables; female, large
tumor size, gross types 3 and 4, moderately or poorly differentiated
adenocarcinomas and signet-ring cell or mucinous carcinomas, deep cancer
invasion, lymphatic invasion, peritoneal and liver metastases, and curability B-C
were found significantly more frequently in the invasive group. The survival
curve of the former was significantly (P < 0.05) lower than that of the latter.
However, no significant difference was found between the survival curves of the
patients with curability A (no residual tumors) in both groups. A multivariate
analysis in the invasive groups revealed six variables to be significantly
related to a good prognosis including a young age, females, a location above the
peritoneal reflection, well differentiated adenocarcinoma, negative lymphatic
invasion, and curability A. Surgery with curability A should be performed to
improve the survival in distal colorectal cancer patients with macroscopic
invasion into the adjacent organs.
PMID- 10192733
TI - Nonfunctioning islet cell carcinoma of the pancreas: an evaluation of seven
patients who underwent resection followed by long-term survival.
AB - Islet cell carcinoma of the pancreas is a rare, indolent malignancy associated
with a higher resectability rate and better survival than ductal carcinoma. This
retrospective study presents the results of surgical treatment for nonfunctioning
islet cell carcinoma of the pancreas in seven patients diagnosed and treated at
Kurume University Hospital. There were two men and five women, with an average
age of 54 years. Of the five tumors, four were located in the head of the
pancreas, and the other three tumors were located in the body or tail of the
pancreas. Epigastric pain was frequently the primary clinical symptom. By the
time of diagnosis, four of the patients had regional disease, one of whom had
lymph node and liver metastases, and one, liver metastases. Another patients was
found to have lymph node metastases intraoperatively. Only one of the patients
died of recurrent cancer, 21 years after the original operation. All of the
patients who had liver metastases at the time of initial surgical treatment are
now living at home. Thus, we conclude that nonfunctioning islet cell carcinomas
are slow-growing tumors with a good prognosis if the main tumors and metastatic
lesions are removed.
PMID- 10192734
TI - Involvement of the #12u lymph nodes around the upper lobe bronchi in patients
with lung cancer of the right middle lobe, right lower lobe, or left lower lobe.
AB - In Japan, the lymph nodes around the upper lobe bronchi, known as the #12u nodes,
are not included in the nodes recommended for dissection in patients with right
middle lobe carcinoma, right lower lobe carcinoma, or left lower lobe carcinoma.
However, histologic examination has revealed involvement of these nodes in
pneumonectomy patients whose carcinoma originated in the right lower lobe. We
histologically examined the lymph nodes from 152 patients with lung cancer to
determine the incidence of involvement of the #12u lymph nodes. These nodes were
found to be involved in 14 (9.2%) of the 152 patients. The rate of involvement
was significantly higher in those with T2-T4 disease than in those with T1
disease, and was also significantly higher in patients with N2 disease than in
those with N1 disease. There were two long-term survivors without recurrence, and
one other patient who lived for more than 5 years before succumbing to the
disease. In conclusion, to ensure removal of all the cancer tissue, it is
recommended that the #12u lymph nodes be included in the nodes routinely
dissected in patients with right lower lobe carcinoma, right middle lobe
carcinoma, or left lower lobe carcinoma.
PMID- 10192735
TI - Three-dimensional computed tomographic angiography in lower extremity
revascularization.
AB - To evaluate the role of three-dimensional computed tomographic angiography (3D
CT) in peripheral artery bypass surgery, 49 patients with chronic lower limb
ischemia underwent 3D-CT before and after a bypass operation. 3D-CT had a
sensitivity of 96.8%, a specificity of 95.0% and an overall accuracy of 96.1% for
the diagnosis of arterial and graft stenosis or obstructions. The ability to
observe the acquired images at any angle was very useful for assessing the
implanted graft in both aortoiliac and infrainguinal bypasses. Although these
images equally identified arterial stenosis, obstruction, and the anastomotic
morphology of bypass grafts as well as conventional angiography, the diagnostic
accuracy was not helpful in the small arteries and grafts. 3D-CT is a low
invasive imaging method that is sufficient for forming strategies for bypass
operations. In aortofemoral or femoropopliteal bypass surgery, 3D-CT thus
provides sufficient imaging accuracy for bypasses up to the popliteal artery
below the knee in patients with chronic limb ischemia.
PMID- 10192736
TI - The effects of a new ultra-short-acting beta-adrenergic blocker, ONO-1101, on
cardiac function during and after cardiopulmonary bypass.
AB - The administration of an ultra-short-acting beta-adrenergic antagonist, esmolol,
has been introduced as a novel method for beating-heart surgery. In the present
study, a new ultra-short-acting beta-blocker, ONO-1101, was administered during
cardiopulmonary bypass (CPB) to investigate its effects on cardiac function and
hemodynamics. Nine adult mongrel dogs underwent 60 min of CPB during which they
were given either ONO-1101 (ONO group; n = 4) or saline (control group; n = 5).
In the ONO group, the hearts became flaccid enough for surgery to be performed
without cardiac standstill within 10 min after the commencement of ONO-1101 with
significant decreases in the heart rate, the preload recruitable stroke work
(PRSW), and the slope of the end-systolic left ventricular pressure-volume
relationship (Emax). The mean arterial pressure and systemic vascular resistance
also decreased, but were maintained above 50 mmHg during CPB without
catecholamine. These indices increased to the control group level 20 min after
the discontinuation of ONO-1101. The serum concentration of ONO-1101 decreased
from the maximum level of 121 +/- 15 microg/ml soon after infusion to 11 +/- 5
microg/ml within 30 min after discontinuation. These data suggest that ONO-1101
may be useful to enable beating-heart surgery to be performed without aortic
cross-clamp as an ultra-short-acting beta-adrenergic blocker.
PMID- 10192737
TI - Platelets as participants in hyperacute guinea pig-to-rat lung xenorejection.
AB - It is well known that xenotransplantation leads to immediate graft dysfunction.
This study was designed to specifically examine the role of platelets in
mediating lung hyperacute xenorejection (HXR) in a guinea pig-to-rat model. A
total of 18 lungs were perfused with blood using an ex vivo apparatus. The
animals were divided into the following four groups: a CE group comprising
circuit only with rat blood; a SYN group comprising rat lungs and blood; a XE
group comprising guinea pig lungs and rat blood; and an SH group comprising
guinea pig lungs and rat blood with sarpogrelate hydrochloride, a suppressor of
platelet aggregation. The platelet and serotonin in the blood were lower and the
wet/dry weight ratio of the lung (W/D) in the XE group were higher than those in
the SYN group after perfusion. The platelet count was higher, but the serotonin
and W/D were lower in the SH group than in the XE group. These results suggest
that platelets strongly affect HXR. Thus, the administration of drugs to suppress
platelet aggregation would reduce xenotransplanted lung edema.
PMID- 10192738
TI - Double cancers of the lung and esophagus associated with a sarcoid-like reaction
in their regional lymph nodes: report of a case.
AB - A case of double cancers of the lung and esophagus associated with a sarcoid-like
reaction in their regional lymph nodes is reported. A 73-year-old man with
hemosputum was found to have a mass in his right lower lung field on a chest X
ray. Based on a diagnosis of lung cancer, a right middle and lower lobectomy with
a dissection of the lymph nodes was performed. Microscopically, a well developed
granulomatous reaction was seen in the dissected mediastinal and hilar lymph
nodes. Three years after the pulmonary resection, he was admitted to our hospital
because of dysphagia. A diagnosis of lower esophageal cancer was made. A lower
esophagectomy with a total gastrectomy was performed. A sarcoid-like reaction
comprising epithelioid cells and giant cells was seen in the regional lymph
nodes. No clinical findings indicative of systemic sarcoidosis were observed.
This rare condition may therefore help to improve our overall understanding of
the relationship between malignant neoplasms and sarcoid-like reactions in the
regional lymph nodes.
PMID- 10192739
TI - Endosalpingiosis of nonmetastatic lymph nodes along the stomach in a patient with
early gastric cancer: report of a case.
AB - We report herein the case of a 32-year-old woman who underwent distal gastrectomy
with D2 lymph node dissection for gastric cancer. Microscopic examination of the
resected specimen revealed signet-ring cell carcinoma of the stomach with lymph
node metastases, and endosalpingiosis in the normal lymph nodes. There was no
evidence of malignancy in the peritoneal cavity. To our knowledge, no other case
of endosalpingiosis in the lymph nodes along the stomach has ever been reported.
The possible significance of endosalpingiosis is discussed following this case
report.
PMID- 10192740
TI - Sigmoid colon cancer presenting as complete rectal prolapse: report of a case.
AB - We describe herein the unusual case of a 76-year-old woman who was diagnosed as
having sigmoid colon cancer after presenting with complete rectal prolapse. The
rectal prolapse was considered to have been caused by constipation accelerated by
the colon cancer. The relationship between colorectal cancer and rectal prolapse
has not yet been clarified; however, this case report suggests that rectal
prolapse can present as a symptom of colorectal cancer. Thus, patients with a
sudden onset of rectal prolapse should be screened for colorectal cancer.
PMID- 10192741
TI - Treatment for accidental occlusion of the hepatic artery after hepatic resection:
report of two cases.
AB - Two patients in whom accidental hepatic artery occlusion (HAO) occurred after
hepatic resection (Hx) were reported. A 59-year-old female who underwent Hx for
hepatocellular carcinoma with underlying liver cirrhosis developed HAO on
postoperative day (POD) 14 and died of hepatic failure on POD 23. The autopsy
findings showed multiple necrosis in the remnant liver and an extraluminal
hematoma of the hepatic artery, suggesting an injury caused by Pringle's
maneuver. The second case was a 53-year-old male who underwent Hx for
cholangiocarcinoma without any underlying liver disease. He developed HAO on POD
6, and radiological studies indicated a pseudoaneurysma formation and severe
stenosis of the hepatic artery. It was speculated that the cause of the HAO was
intraluminal injury of the hepatic artery during an angiographic study conducted
prior to Hx. Partial arterialization of the portal vein was performed, following
which his liver function test results improved. In both cases, measuring the
serum hepatocyte growth factor level and the hepatic vein oxygen saturation
proved useful, not only for determining the degree of liver injury, but also for
predicting the outcome after treatments for HAO. Furthermore, the partial
arterialization of the portal vein for HAO after Hx may rescue the normal remnant
liver.
PMID- 10192742
TI - Isolated colonic tuberculous perforation as a rare cause of peritonitis: report
of a case.
AB - We present herein the rare case of a patient who developed peritonitis due to
colonic tuberculosis with perforation. The patient was successfully treated by
resectional surgery with delayed restoration of bowel continuity and
antitubercular therapy.
PMID- 10192743
TI - Quadruple cancer including bilateral breasts, Vater's papilla, and urinary
bladder: report of a case.
AB - We herein report a rare case of quadruple carcinoma with heterochronous bilateral
breast cancer, cancer of Vater's papilla, and cancer of the urinary bladder,
which were all curatively resected. A 62-year-old woman previously underwent
right and left modified radical mastectomies heterochronously. Recently, a
dilatation of the lower bile duct, diagnosed as cancer of Vater's papilla, was
resected by a pancreatoduodenectomy. Hematuria during surgery led to the
discovery of a solid bladder tumor. The tumor was resected by a transurethral
resection. The histopathologic findings differed for all four lesions. The
patient had an uneventful postoperative course and to date has shown no
recurrence.
PMID- 10192744
TI - Conservative management of a methicillin-resistant Staphylococcus aureus (MRSA)
infected aortobifemoral graft: report of a case.
AB - A 63-year-old man was referred to our department for treatment of intermittent
claudication in the right lower limb. The preoperative angiogram showed severe
stenosis extending from the terminal aorta to the bilateral common femoral
arteries, with occlusion of the right superficial femoral artery and the left
popliteal artery. He underwent aortobifemoral bypass with thromboendarterectomy
of the left common femoral artery, and right graft-popliteal artery bypass. The
patient had an uneventful postoperative course; however, 14 days after the
operation, a pulsatile mass suddenly appeared in the left groin. Emergency
surgery revealed disruption of the left distal anastomosis of the aortobifemoral
bypass and therefore, revision, in the form of graft-profunda femoris artery
interposition with graft-superficial femoral artery bypass, was performed.
Microscopic examination showed colonies of bacteria in the host artery adventitia
adjacent to the anastomosis. Culture of the discharge from the right groin
operative scar revealed methicillin-resistant Staphylococcus aureus (MRSA). The
discharge resolved following the intravenous administration of vancomycin and the
local application of vancomycin ointment. There were no operative complications
other than the MRSA infection, and the patient was discharged 20 days after
revision surgery. In the 14 months since the revision, all grafts have remained
patent and there have been no further symptoms of graft infection.
PMID- 10192745
TI - Conversion of right atrioventricular to total cavopulmonary anastomosis in the
management of post-Fontan arrhythmia: report of a case.
AB - Both the original and modified Fontan procedures are associated with several late
complications such as atrial arrhythmias, thromboembolism, and right pulmonary
vein compression caused by a markedly enlarged right atrium. We describe herein
the case of a patient who underwent conversion of right atrioventricular to total
cavopulmonary anastomosis to control atrial arrhythmia that developed 12 years
after a modified Fontan operation. The procedure proved successful in alleviating
his symptoms immediately. He is now doing well with no recurrence of atrial
arrhythmia 1 year after the operation.
PMID- 10192746
TI - Interleukin-1alpha concentration in tumors as a risk factor for liver metastasis
in gastric cancer.
AB - To investigate the relationship between the concentration of interleukin-1alpha
(IL-1alpha) and liver metastasis in gastric cancer, the concentration of IL
1alpha was measured in homogenized tumor samples from 61 patients with gastric
cancer. A significantly higher concentration of IL-1alpha was observed in tumors
from patients with liver metastasis than in those from patients without liver
metastasis; in differentiated type tumors than in undifferentiated type tumors;
in tumors associated with moderate to severe venous invasion than in those
associated with mild or no invasion; and in tumors with expansive or intermediate
growth pattern (INFalpha, INFbeta) than in those with an infiltrative pattern
(INFgamma) by Student's t-test. Stepwise logistic regression revealed IL-1alpha,
depth of invasion, venous invasion, and tumor size to be associated independently
with liver metastasis. These findings led us to conclude that the IL-1alpha
concentration was on eof the most useful determinants of liver metastasis among
the various clinicopathologic characteristics.
PMID- 10192748
TI - Clomipramine concentration as a predictor of delayed response: a naturalistic
study.
AB - OBJECTIVES: The aim of the present study was to characterise onset of response to
clomipramine treatment in a naturalistic setting and to investigate the
relationship between concentration and delayed response, postulated to reflect
drug-specific response to antidepressant therapy. METHODS: Ninety-eight depressed
patients were prescribed clomipramine in an open flexible manner and followed for
depressive symptoms (Montgomery-Asberg depression scale) over a maximum 12 weeks
follow-up period. All patients had at least one concentration measurement for
therapeutic drug monitoring purpose. RESULTS: Firstly, survival analysis revealed
a probability of 15.4% for patients not to show 50% improvement over baseline by
week 12, and thus to be considered as non-responders. Median time to onset of
response was 31 days for responders, indicating a relatively high probability of
delayed response under routine treatment. Secondly, pattern analysis indicated a
significant association between early and abrupt response on the one hand and
delayed and gradual response on the other. A tendency towards an association
between delayed and persistent response was also observed. Finally, receiver
operating characteristics analysis allowed identification of a highly significant
lower threshold of 230 ng x ml(-1) for the sum of clomipramine and desmethyl
clomipramine, as measured at week 3, with respect to response from week 3 onward.
Predictive values were 68.8% and 81.0% for concentrations above and below this
threshold to predict delayed response and non-response, respectively. Thresholds
were 55 ng x ml(-1) for parent compound and 180 ng x ml(-1) for metabolite.
CONCLUSION: This approach supports the hypothesis that delayed response may be
concentration dependent and thus may reflect true drug effect. As a consequence,
monitoring clomipramine concentration about 3 weeks after initiation of therapy
may valuably contribute to help clinicians decide about the adequacy of ongoing
therapy.
PMID- 10192747
TI - The effectiveness of perineal rectosigmoidectomy for the treatment of rectal
prolapse in elderly and high-risk patients.
AB - We report herein on the follow-up of ten consecutive patients who underwent
perineal rectosigmoidectomy, and discuss the indications, surgical technique, and
outcomes of this procedure. The median age of the patients was 79 years, with a
range of 26 to 85 years, and eight patients had complicating medical conditions.
Of five patients who underwent this procedure for a recurrent prolapse after
another type of perineal procedure, four had previously undergone the Thiersch
operation combined with the Gant-Miwa technique. The mean length of the excised
rectum and sigmoid colon was 22.1 cm. Pain was minimal or absent in all patients
and oral intake was commenced after 2 days. There were no mortalities, but
anastomotic leakage occurred in one patient. The mean follow-up period was 3.5
years. Only one patient developed recurrent rectal prolapse 24 months after the
operation. Of seven patients who underwent concomitant levatoroplasty for
incontinence, five became fully continent within 3 weeks after the operation,
while the remaining two improved after 2 months. We propose that perineal
rectosigmoidectomy is indicated for patients who have suffered an early
recurrence of prolapse after another transperineal repair; elderly or high-risk
patients with incontinence; male patients; and patients with an incarcerated or
gangrenous prolapsed rectal segment.
PMID- 10192750
TI - Cytosolic calcium and lymphoproliferative response during calcium antagonism in
men.
AB - OBJECTIVE: A double-blind, placebo-controlled parallel study was conducted on the
effect of mibefradil, both an L- and T-type Ca2+-channel blocker with a more
selective blockade of T-type channels, administered once daily for 1 week to
normal male subjects, on blood pressure, intracellular cationic concentrations,
sodium-proton exchange rate and 3H-thymidine incorporation in peripheral blood
mononuclear cells (PBMC). METHODS: After a 1-week run-in period on placebo, the
subjects (n = 40) were allocated to a placebo or a mibefradil group. Placebo or
50 mg mibefradil was administered once daily in the morning for 1 week. All
subjects were investigated at baseline and after 1 week of placebo or mibefradil
administration. Standing or recumbent blood pressure and heart rate of subjects
in the mibefradil group was decreased (P < 0.05 or less) compared with that of
subjects in the placebo group. RESULTS: Decreased (P < 0.001) intracellular free
Ca2+ concentration and reduced (P < 0.001) 3H-thymidine incorporation in the PBMC
were observed in the mibefradil-treated subjects. The intracellular sodium,
potassium or magnesium concentration as well as the sodium-proton exchange rate
were not changed during mibefradil administration. CONCLUSION: The blood pressure
lowering action of mibefradil in men is accompanied by a decrease in
intracellular free Ca2+ concentration. Mibefradil also reduced the 3H-thymidine
incorporation or de novo DNA synthesis in PBMC by modulating the calcium
homeostasis.
PMID- 10192749
TI - The effect of the apolipoprotein E phenotype on cholesteryl ester transfer
protein activity, plasma lipids and apolipoprotein A I levels in
hypercholesterolaemic patients on colestipol and lovastatin treatment.
AB - BACKGROUND: Apolipoprotein E (apo E) allele E 4 is associated with high
atherogenic lipid levels and coronary heart disease. Cholesteryl ester transfer
protein (CETP) transfers cholesteryl esters from (high density lipoprotein) HDL
to other lipoproteins. CETP gene expression is enhanced in hypercholesterolaemia
and correlates with plasma apo E concentration. OBJECTIVE: The effect of the apo
E phenotype on plasma CETP activity and the hypolipidaemic efficacy of colestipol
and lovastatin was studied in patients with type II a or II b
hypercholesterolaemia. RESULTS: The baseline mean plasma total, low density
lipoprotein (LDL) and HDL cholesterol, triglyceride, apolipoprotein A I (apo A I)
concentrations and CETP activity were 8.89 mmol x l(-1), 6.78 mmol x l(-1), 1.39
mmol x l(-1), 1.59 mmol x l(-1), 1.49 g x l(-1) and 114 nmol x h(-1) x ml(-1),
respectively. The colestipol-induced changes were -26%, -36%, +5%, + 12%, -1% and
-17%, and the lovastatin-induced changes -34%, -44%, +6%, -18%, +1% and -19%. The
lipid and apo A I concentrations or the CETP activity did not differ
statistically significantly according to the apo E phenotype, although the HDL
cholesterol and apo A I levels were lowered in patients with apo E 4/4 but
elevated in patients with the other phenotypes. The CETP activity correlated with
the LDL cholesterol concentration (r = 0.52, P = 0.01) and the change in the LDL
cholesterol during colestipol (r = 0.51, P = 0.02) and lovastatin (r = 0.65, P =
0.001) treatment, but only in patients without the apo E 4 allele. CONCLUSION:
Colestipol and lovastatin reduced CETP activity to the same amount, regardless of
the apo E phenotype. The apo E phenotype seems to modify the interaction between
CETP activity and LDL cholesterol in hypercholesterolaemia and during
pharmacological lowering of cholesterol.
PMID- 10192751
TI - Topical heparin for the treatment of acute superficial phlebitis secondary to
indwelling intravenous catheter. A double-blind, randomized, placebo-controlled
trial.
AB - OBJECTIVE: To assess the clinical efficacy of a topical gel containing 1000 IU x
g(-1) of heparin, applied three times daily for a maximal period of 7 days to
patients with acute superficial phlebitis secondary to indwelling intravenous
catheter. METHODS: A Double-blind, randomized, placebo-controlled study was
conducted in one of the internal medicine wards of a tertiary General Hospital in
Barcelona, Spain. Inpatients of both genders over 18 years of age that developed
superficial phlebitis and gave informed consent were included in the study. The
sample size estimation was 132 patients. Sixty-six patients were allocated to
each group. There were five protocol deviations and 24 withdrawals in the
intervention group, and one protocol deviation and 25 withdrawals in the control
group. Consequently, 37 patients in the intervention group and 40 in the control
group completed the trial. The main outcome measure was the disappearance of the
symptoms and signs of superficial phlebitis. Clinical course, investigator's
global impression and adverse events were also recorded. RESULTS: According to
the intention-to-treat analysis, after treatment for 7 days superficial phlebitis
healed in 27 of the 61 patients (44.3%) who received topical heparin, and in 17
of the 65 patients (26.1%) receiving placebo, giving a relative risk [95%
confidence interval (CI)] of 1.69 (1.03-2.78). This indicates that six patients
(95% CI, 3-72) have to be treated in order to induce one additional healing. The
clinical course and the overall clinical impression were similar in both groups.
One patient treated with topical heparin developed mild urticaria. CONCLUSION:
Topical heparin is safe and effective for the treatment of superficial phlebitis
secondary to indwelling intravenous catheter.
PMID- 10192752
TI - Pharmacokinetic evaluation of co-administration of nefazodone and lithium in
healthy subjects.
AB - OBJECTIVES: To evaluate the possible pharmacokinetic interaction between
nefazodone and lithium. METHODS: Twelve healthy volunteers received nefazodone
200 mg b.i.d. for 5 days. A 4-day washout phase followed from day 6 to day 9.
From day 10 to day 20, escalating doses of lithium 250 mg b.i.d. to 500 mg b.i.d.
were given; the daily dose of 1000 mg was obtained on day 13. From day 16 to day
20, nefazodone 200 mg b.i.d. was added to the lithium dosing regimen. Venous
blood sampling was performed on days 5, 15 and 20 for 0- to 48-h-pharmacokinetic
analysis. Nefazodone and its metabolites, hydroxynefazodone, mCPP and
triazoledione were assayed by high-performance liquid chromatography (HPLC).
Lithium was assayed by flame photometry. RESULTS: Co-administration of nefazodone
did not modify pharmacokinetic parameters of lithium at steady-state. Comparison
of the area under the plasma or serum concentration-versus-time curve calculated
from 0-12 h (AUC0-12) of nefazodone and hydroxynefazodone revealed no significant
differences when nefazodone was administered alone or with lithium. The mean
maximum peak plasma concentration Cmax and AUC0-12 of meta-chlorophenyl
piperazine (mCPP) were significantly reduced by 27% (P < 0.001) and 16% (P <
0.001) with the co-administration. The mean Cmax and AUC0-12 of triazoledione
were reduced by 23% (P < 0.005) and 16% (P < 0.01) by the co-administration.
CONCLUSION: Since there were no clinically significant changes in the
pharmacokinetics of the parent compounds or metabolites, and the combination was
well tolerated, no dosage adjustments of nefazodone or lithium are necessary when
they are co-administered.
PMID- 10192753
TI - The oral bioavailability of pentosan polysulphate sodium in healthy volunteers.
AB - OBJECTIVE: Pentosan polysulphate sodium (PPS), a heparin-like drug, is supposed
to be orally applicable. The objective of the present study was to assess the
oral bioavailability of PPS. However, since specific assays for PPS do not exist,
this was done by using primary and secondary effect parameters. METHODS: The
study was carried out using a three-way randomized crossover design with 18
healthy young male volunteers. The subjects received three treatments: PPS i.v.
(50 mg), PPS orally (1500 mg) and placebo (orally). Blood sampling was done for
activated partial thromboplastin time (APTT), anti-Xa activity, hepatic
triglyceride lipase, lipoprotein lipase, tissue plasminogen activator (t-PA)
activity, fibrin plate lysis, total triglyceride, total cholesterol, HDL and LDL.
RESULTS: Intravenously administered PPS significantly increased APTT, anti-Xa
activity, hepatic triglyceride lipase and lipoprotein lipase compared with
placebo in a magnitude comparable to other i.v. heparin-like compounds. Orally
administered PPS did not significantly influence any of the parameters when
compared with placebo. Point estimates for the oral bioavailability of PPS were
in the range of 0% with small confidence intervals (CIs). CONCLUSION: The oral
bioavailability of PPS is negligible in young healthy males.
PMID- 10192754
TI - Plasma esterases in cystic fibrosis: the impact of a respiratory exacerbation and
its treatment.
AB - OBJECTIVES: To determine the effect of an exacerbation of respiratory symptoms in
cystic fibrosis (CF) on the activities of plasma benzoylcholinesterase and
butyrylcholinesterase. METHODS: Twenty-nine patients with CF in a respiratory
exacerbation and 27 healthy volunteers matched for age and sex were recruited.
Blood was obtained from the patients when commencing antibiotic treatment and 14
days later on completion of treatment. One blood sample was taken from the
healthy volunteers. The activities of benzoylcholinesterase and
butyrylcholinesterase were determined by spectrophotometric assay. The
circulating inflammatory markers, C-reactive protein and neutrophil elastase
alpha1antiproteinase complex were also measured. RESULTS: Benzoylcholinesterase
activity was significantly (P = 0.001) lower in patients at the start of a
respiratory exacerbation, compared with healthy controls [mean (SD): 917 (274)
versus 1191(298) nmol x ml(-1) x min(-1)]. Benzoylcholinesterase activity
increased significantly in patients to 1013 (237) nmol x ml(-1) x min(-1),
following a course of antibiotic treatment (P = 0.006). Butyrylcholinesterase
activity was also lower (P = 0.001) in patients at the start of a respiratory
exacerbation, compared with healthy controls [5.54 (1.64) versus 7.01 (1.79)
micromol x ml(-1) x min(-1)], and increased significantly in the patients to 6.31
(1.58) micromol x ml(-1) x min(-1) following treatment (P = 0.006). CONCLUSION:
We demonstrated significant suppression of plasma esterase activities during an
exacerbation of respiratory symptoms in CF, which was only partially reversed
after antibiotic treatment. Further studies are needed to examine other pathways
of drug metabolism in this group of chronically infected patients.
PMID- 10192755
TI - Lack of correlation between fluvoxamine clearance and CYP1A2 activity as measured
by systemic caffeine clearance.
AB - OBJECTIVE: Evidence exists to suggest that fluvoxamine is metabolized by CYP1A2.
The present study was undertaken in order to further elucidate the role of CYPIA2
in fluvoxamine disposition. METHODS: Twelve healthy non-smoking male volunteers
participated in this cross-over study. Six subjects received first fluvoxamine 50
mg as a single oral dose and, some weeks later, caffeine 200 mg as a single oral
dose. The other six subjects received the drugs in reverse order. Serum
concentrations of fluvoxamine, caffeine and paraxanthine were measured and
standard pharmacokinetic parameters were calculated. RESULTS: There were no
significant correlations between caffeine clearance and fluvoxamine oral
clearance (rs = -0.30; P = 0.43) or between the paraxanthine/caffeine ratio in
serum 6 h after caffeine intake and fluvoxamine oral clearance (rs = -0.18; P =
0.58). CONCLUSION: CYP1A2 does not appear to be of major importance in the
metabolism of fluvoxamine.
PMID- 10192756
TI - Inhibition of CYP2C9 by selective serotonin reuptake inhibitors: in vitro studies
with tolbutamide and (S)-warfarin using human liver microsomes.
AB - OBJECTIVE: To investigate the in vitro potential of selective serotonin reuptake
inhibitors (SSRIs) to inhibit two CYP2C9-catalysed reactions, tolbutamide 4
methylhydroxylation and (S)-warfarin 7-hydroxylation. METHODS: The formation of 4
hydroxytolbutamide from tolbutamide and that of 7-hydroxywarfarin from (S)
warfarin as a function of different concentrations of SSRIs and some of their
metabolites was studied in microsomes from three human livers. RESULTS: Both
tolbutamide 4-methylhydroxylation and (S)-warfarin 7-hydroxylation followed one
enzyme Michaelis-Menten kinetics. Kinetic analysis of 4-hydroxytolbutamide
formation yielded a mean apparent Michaelis-Menten constant (Km) of 133 microM
and a mean apparent maximal velocity (Vmax) of 248 pmol x min(-1) x mg(-1);
formation of 7-hydroxywarfarin yielded a mean Km of 3.7 microM and a mean Vmax of
10.5 pmol x min(-1) x mg(-1). Amongst the SSRIs and some of their metabolites
tested, only fluvoxamine markedly inhibited both reactions. The average computed
inhibition constant (Ki) values and ranges of fluvoxamine when tolbutamide and
(S)-warfarin were used as substrate, were 13.3 (6.4-17.3) microM and 13.0 (8.4
18.7) microM, respectively. The average Ki value of fluoxetine for (S)-warfarin 7
hydroxylation was 87.0 (57.0-125) microM. CONCLUSION: Amongst the SSRIs tested,
fluvoxamine was shown to be the most potent inhibitor of both tolbutamide 4
methylhydroxylation and (S)-warfarin 7-hydroxylation. Fluoxetine, norfluoxetine,
paroxetine, sertraline, desmethylsertraline, citalopram, desmethylcitalopram had
little or no effect on CYP2C9 activity in vitro. This is consistent with in vivo
data indicating that amongst the SSRIs, fluvoxamine has the greatest potential
for inhibiting CYP2C9-mediated drug metabolism.
PMID- 10192757
TI - Pharmacokinetics and pharmacodynamics of candesartan cilexetil in patients with
normal to severely impaired renal function.
AB - OBJECTIVE: We studied the pharmacokinetics and pharmacodynamics of single and
multiple doses of candesartan cilexetil 8 mg per day in hypertensive patients
with different degrees of renal function impairment. Candesartan is an
angiotensin II subtype 1 (AT1) receptor antagonist that is administered orally as
candesartan cilexetil which is converted in the active compound. METHODS: Twenty
three patients were included, divided into groups according to creatinine
clearance (cr cl. group A >60 nl x min(-1) x 1.73 m(-2), group B 30-60 ml x min(
1) x 1.73 m(-2) and group C 15-30 ml x min(-1) x 1.73 m(-2)). RESULTS: Trough
serum concentrations of candesartan were higher in group C compared with group A.
The values did not increase after multiple dosing, indicating absence of
accumulation. There was a significant negative correlation between the area under
the concentration-time curve extrapolated to time infinity (AUCinf) and the
glomerular filtration rate (GFR) indicating a lower renal clearance of
candesartan in patients with impaired renal function. The onset of haemodynamic
and hormonal effects was gradual. During the single-dose study blood pressure as
well as plasma renin activity (PRA) and angiotensin II were unchanged at peak. At
day 5 of the multiple-dose study blood pressure was lower and both PRA and
angiotensin II were higher compared with baseline. CONCLUSION: Although serum
trough levels increased during repeated administration and half-life was higher
in patients with impaired renal function, candesartan cilexetil at a dose of 8 mg
per day does not lead to drug accumulation in these patients. This dose is
effective in lowering blood pressure and appears to be suitable for patients with
renal function impairment.
PMID- 10192758
TI - Suspected adverse drug events requiring emergency department visits or hospital
admissions.
AB - OBJECTIVE: To analyse the contribution of adverse drug events (ADEs) to the
overall number of referrals or visits at an emergency department, to determine
the proportion of more severe episodes requiring hospital admission and to
characterize the different causes of drug-related visits or admissions. METHODS:
A 1-year prospective collection of data on visits performed at an emergency
department. All visits, observed during 1 week every month, were analyzed in
order to identify suspected ADEs. The effects of age and sex on the frequency of
ADE-related visits and admissions were evaluated. All patients hospitalized
because of an ADE were followed up in order to collect information about progress
and outcome of the events, which were also assessed in terms of avoidability.
RESULTS: Among the 5497 patients who visited the Emergency Department over 1
year, 235 (4.3%) experienced an ADE, 45 of these (19.1%) were subsequently
hospitalized, among whom there were five deaths. Dose-related therapeutic
failures were the main causes of drug-related admissions (55.6%), whereas adverse
drug reactions caused the most frequent drug-related visits to the Emergency
Department (63.8%). Although the frequency of drug-drug interactions leading to a
visit to the Emergency Department was small (3.8%), this type of event was more
severe, because most of these patients were hospitalized. No age/sex effect was
observed in the proportion of ADE-related hospital admissions. Twenty-five (1.4%
of the total admissions) of the 45 ADE-related admissions were evaluated as
preventable, contributing by more than 61% of the overall length of hospital
stay. CONCLUSION: The high proportion of drug therapeutic failures leading to an
admission highlights the need for public education, particularly to prevent non
compliance.
PMID- 10192759
TI - Use of laxatives in institutions for the mentally retarded.
AB - OBJECTIVE: To study, in institutionalized mentally retarded patients, the
prevalence of regular laxative use, and to identify its correlates. METHODS:
Twenty-one of the 22 institutions for the mentally retarded in Flanders (Belgium)
provided the setting for the study, which included a population of 3712 residents
with an IQ of < 50. This was a descriptive cross-sectional study of a random
sample of 20 patients per institution, consisting of a structured interview of
the personnel responsible for daily care of the selected patients. The study
population consisted of 420 mentally retarded patients. Their median age was 29
years (range 2-72 years). Twenty-six percent of patients had an IQ of 35-49, 40%
an IQ of 20-34 and 34% an IQ of <20. Sixteen percent of the patients were non
ambulant. RESULTS: Regular laxative use was found in 26.4% (111/420) of the
residents. In addition, occasional laxative use was found in 2% (10/420) of the
residents. Oral laxatives were used daily by 13% (56/420) and oral laxatives
daily in combination with enemas were used by 9% (39/420). Enemas but no oral
laxatives were used by 3% (11/420); manual evacuation in combination with oral
laxatives and enemas was used by 1% (5/420). Seventy-eight percent (78/100) of
the oral laxative users used them for more than 1 year. Seventy-one percent
(71/100) used one laxative, 23% two and 6% three. Thirty different brands of oral
laxatives were used. Sixty-seven percent (67/100) used osmotic laxatives alone or
in combination, 30% used stimulant laxatives, 19% used bulk forming laxatives and
19% mineral oil. Oral laxatives were always prescribed by attending physicians,
while enemas were also initiated by nurses in 35% (18/52). Laxative use was
positively and independently correlated with female gender, with being non
ambulant, with oral motor dysfunction and with the use of medication other than
laxatives. It did not correlate with age. Within the institutions, laxative use
varied from one to 15 users out of the 20 randomly selected patients (median
4/20). CONCLUSION: Laxative use is frequent in institutions for the mentally
retarded, with a large inter-institution variation, indicating that constipation
is an important problem and underlining the need for research into cost-effective
treatment.
PMID- 10192760
TI - Influence of phospholipid composition on the properties of reconstituted
surfactants.
AB - The influence of phospholipids on the ultrastructure and metabolism of
reconstituted surfactants has not been well defined. The aim of this study was to
determine if changes in the phospholipid composition of reconstituted surfactants
altered their biophysical properties, ultrastructure, and conversion to light
subtype by cycling. We prepared various surfactants containing radiolabeled
dipalmitoylphosphatidylcholine ([14C]DPPC). The addition of phosphatidylglycerol
(PG) or dipalmitoylphosphatidic acid (PA) to DPPC increased conversion to light
subtype. In contrast, the addition of dipalmitoylphosphatidylglycerol (DPPG) to
DPPC markedly reduced conversion to light subtype on cycling. DPPC and DPPC+PG
produced large liposomes ( approximately 1,000 nm), whereas DPPC+PA or DPPC+DPPG
formed multilamellar membranes. Mixtures of DPPC and PA were highly surface
active in vitro, whereas the surface activity of DPPC+DPPG was similar to that of
DPPC. In conclusion, the ultrastructure, metabolism, and surface active
properties of DPPC+PG mixtures were influenced markedly by alterations in the
fatty acid composition or polar head group of PG.
PMID- 10192761
TI - 1,25-dihydroxycholecalciferol stimulates ICAM-1 expression of human alveolar
macrophages in healthy controls and patients with sarcoidosis.
AB - Synthesis and release of 1,25-dihydroxycholecalciferol (1, 25-(OH)2D2) by
alveolar macrophages (AM) have been shown to be increased in granulomatous lung
disease. ICAM-1 plays a major part in leukocyte homing to sites of chronic
inflammation, which is a crucial step during the inflammatory response. Whether
1,25-(OH)2D2 alters the ICAM-1 expression of AM in humans has not been studied.
Bronchoalveolar lavage (BAL) was performed in 12 healthy volunteers, in 13
patients with sarcoidosis (active disease n = 8, inactive disease n = 5), and in
9 patients with chronic bronchitis. AM were incubated with different
concentrations of 1,25-(OH)2D2 (10(-11) to 10(-6) M) with and without priming
with interferon-gamma (IFN-gamma) and with and without preincubation with 10(-8)
M dexamethasone. In addition, the metabolites of vitamin D, 24, 25
dihydroxycholecalciferol and 25-hydroxycholecalciferol, were used. The AM
expression of ICAM-1 (cELISA) and the release of tumor necrosis factor-alpha (TNF
alpha) (bioassay) by AM were determined. In healthy volunteers the ICAM-1
expression on AM was significantly and dose-dependently increased by 1,25
(OH)2D2, but not by 24, 25-dihydroxycholecalciferol and 25
hydroxycholecalciferol. Priming with IFN-gamma resulted in an additive effect.
Preincubation with dexamethasone inhibited ICAM-1 expression. Addition of 1,25
(OH)2D2 after inhibition by dexamethasone increased ICAM-1 expression
significantly. TNF-alpha secretion of AM from healthy volunteers was
significantly reduced by 1,25-(OH)2D2. In sarcoidosis patients ICAM-1 expression
was significantly higher compared with healthy volunteers. Incubation with 1,25
(OH)2D2 resulted in a further significant increase of ICAM-1 expression. TNF
alpha secretion of AM was increased compared with healthy volunteers. 1,25
(OH)2D2 reduced TNF-alpha secretion; however, this difference was not
significant. 1, 25-(OH)2D2 has an immunomodulating effect on human AM both in
healthy volunteers and in sarcoidosis patients with enhanced expression of ICAM
1. It may serve as an autocrine mediator in inflammatory lung disease.
PMID- 10192762
TI - Age and bronchial hyperresponsiveness are associated with failure to perform the
single breath N2 test in a rural female population.
AB - Because some authors have reported high rates of failure in performing the single
breath N2 (SBN2) test in rural areas, the present study aimed at evaluating its
acceptability in a female population, unfamiliar with lung function testing, in a
rural area of northeastern France. Two hundred ninety-eight women from a rural
area volunteered for a preventive medicine examination (91.6% of those invited);
four of them were excluded for clinical reasons, and six (2%) were unable to
perform spirometry. The protocol included completion of a questionnaire,
spirometry with a bronchial reactivity test, skin prick test, and the SBN2 test
utilizing a computerized assembly. Although failures caused by the apparatus were
few (n = 7, 2.4%) 96 of 281 women (34.1%) were unable to produce two valid SBN2
tests in a series of six attempts. Compared with the group who succeeded in the
test (n = 185), women who failed were older and had a higher prevalence of
bronchial hyperresponsiveness. Logistic regression confirmed the independent
association of these two variables with an inability to perform. We conclude that
in a female population completely unfamiliar with lung function testing the SBN2
test has a high rate of failure associated with higher age and the presence of
bronchial hyperresponsiveness.
PMID- 10192763
TI - Serum lysozyme levels and clinical features of sarcoidosis.
AB - Serum lysozyme is used as a marker of sarcoidosis disease activity. In this study
we examined the association between lysozyme levels and the clinical features of
sarcoidosis and thus the clinical usability of this parameter in a large
population. One hundred ten sarcoidosis patients from central Japan were examined
for clinical features and serum lysozyme level at the first visit to our hospital
and on a regular basis thereafter. The sensitivity of lysozyme for predicting
sarcoidosis was 79.1%, whereas that of serum angiotensin-converting enzyme (ACE)
was 59.0%. Even in the cases without an elevated serum ACE level, a value of
72.1% was obtained. The serum lysozyme level demonstrated a significant tendency
to increase with the number of organs involved (p < 0.01). There were significant
differences among the four radiographic stages (p < 0. 05). The maximum serum
lysozyme levels of patients without a disappearance of abnormal shadows on chest
radiography within 5 years were significantly greater than those of individuals
with a disappearance (p < 0.05). A positive correlation between serum lysozyme
and serum ACE levels was observed. Because serum lysozyme is much less specific
for sarcoidosis than serum ACE, its diagnostic value may be limited. However, the
sensitivity was high even when serum ACE levels were within normal limits and
correlated well with clinical features in sarcoidosis. Therefore, this parameter
seems suitable for disease monitoring in proven cases.
PMID- 10192764
TI - Lack of correlation between nonspecific nasal and bronchial reactivity in
allergic rhinitis subjects.
AB - A link between allergic rhinitis and asthma has long been suspected, allergic
rhinitis being considered a precursor of asthma. The hypothesis is that if such a
link exists, then nonspecific nasal and bronchial reactivity are already
correlated in acute rhinitis patients. To test for this correlation, we compared
nonspecific nasal and bronchial reactivity in two groups of rhinitis subjects: 37
rhinitis pollinosis patients tested during the pollen season and 35 rhinitis
pollinosis patients tested outside the pollen season. We also assessed how
smoking affects this link. In each subject, allergy, nonspecific nasal, and
nonspecific bronchial reactivity were tested, and smoking was categorized. We
found no correlation between nonspecific nasal and bronchial reactivity in the
two nonasthmatic rhinitis groups. During active allergic inflammation (pollinosis
season) no shift toward a stronger link between upper and lower airways can be
found compared with the latent period (out of pollinosis season). Unexpectedly,
among smokers we found a significant relationship between nonspecific nasal and
bronchial reactivity. Thus, there is not yet sufficient evidence for a
straightforward link between nasal and bronchial hyperreactivity in nonasthmatic
pollinosis rhinitis subjects. The development of asthma seems to be crucial for
this link.
PMID- 10192765
TI - Oxidative inactivation of surfactants.
AB - Reactive oxygen species (ROS) may play an important role in the chronic pulmonary
morbidity of preterm infants. We therefore studied the magnitude and mechanisms
of oxidative inactivation of a natural lung surfactant (NLS) and of two
surfactants used for treatment of respiratory distress syndrome, beractant and
KL4 surfactant (KL4). Incubation with Fenton reagents, 2-4 mM peroxynitrite (ONOO
) or 0.5 mM hypochlorous acid (OCl-), resulted in an increased minimum surface
tension (MST) of all surfactants; the order of effect on MST was beractant > KL4
> NLS. After incubation with Fenton reagents, NLS contained a higher
concentration of conjugated dienes (p < 0.01) but lower concentration of
malondialdehyde (p < 0.001) than beractant. Protein carbonyl concentrations after
treatment with Fenton reagents were higher in NLS and KL4 than in beractant (p <
0. 05). Surface area cycling for 24 h with 2 mM ONOO- or 0.5 mM OCl- caused both
beractant and KL4 to increase the proportion of light subtypes from 8-10% to 26
29%; with Fenton reagents, there was disappearance of the light subtype and
formation of ultraheavy subtype 74-91% with poor MST. Natural and therapeutic
surfactants differ markedly in their sensitivity to ROS, which may be important
for surfactants in therapeutic use because oxidative inactivation may limit their
effect. Oxidation of natural surfactant may result in reduced function and
contribute to chronic lung disease.
PMID- 10192766
TI - Bronchial hyperresponsiveness in farmers: relation to respiratory symptoms, lung
function, and atopy.
AB - There is only limited information on the factors associated with nonspecific
bronchial hyperresponsiveness (BHR) in farmers. Our purpose was to examine the
relationship between BHR and respiratory symptoms, atopy, and abnormalities of
lung function in a sample of French farmers. Farmers scheduled for a preventive
medicine check-up in northeastern France were examined. Occupational exposure,
respiratory symptoms, and work-related symptoms were assessed by questionnaire,
sensitization to 34 common and agricultural allergens by skin prick tests, and
BHR by the single-dose (1,200 microg) acetylcholine (ACh) challenge test. Data
were obtained from 741 farmers (95% of those invited). Seventy-seven subjects
(10.3%) had BHR defined as a fall in forced expiratory volume in 1 s (FEV1) >/=
10% after the inhalation of ACh or, for those with a poor lung function, an
increase in FEV1 > 10% and > 200 ml after the inhalation of 200 microg of
salbutamol. The proportion of asthmalike symptoms, especially wheeze during work,
positive skin tests to acarian (storage mites) and cereal dust allergens, and low
levels of lung function was significantly greater among reactors than among
nonreactors. Stepwise logistic regression analysis showed a significant and
independent association between BHR and wheezing during work (OR = 4.99; 95% CI =
2.29-10.89; p = 0.0001) and baseline FEV1 (OR = 1.49; 95% CI = 1.05-2.20; p =
0.026). In conclusion, hyperreactive farmers had significantly more asthmalike
symptoms, positive skin tests, and abnormal lung function than normoreactive
farmers. Work-related wheeze and low baseline FEV1 were significantly and
independently associated with BHR.
PMID- 10192767
TI - GGF/neuregulin induces a phenotypic reversion of oligodendrocytes.
AB - We have previously shown that glial growth factor (GGF), a member of the
neuregulin (NRG) family of growth factors, is a mitogen and survival factor for
oligodendrocyte progenitors in cell culture and blocks their differentiation at
the pro-oligodendrocyte stage (P. D. Canoll et al., 1996, Neuron 17, 229-243). We
now show that GGF is able to induce differentiated oligodendrocytes to undergo a
phenotypic reversion characterized by loss of MBP expression, reexpression of the
intermediate filament protein nestin, reorganization of the actin cytoskeleton,
and a dramatic reduction in the number of processes per cell. TUNEL analysis
demonstrates that GGF is not cytotoxic for mature oligodendrocytes, but rather
enhances their survival. GGF also induces the rapid activation of the PI 3-kinase
and MAP kinase signaling pathways. These results further support a role for the
NRGs in promoting the proliferation and survival of and inhibiting the
differentiation of cells in the oligodendrocyte lineage and demonstrate that
oligodendrocytes that differentiate in culture retain a substantial degree of
phenotypic plasticity.
PMID- 10192768
TI - Synoretin--A new protein belonging to the synuclein family.
AB - Aoffa-Synuclein, a presynaptic nerve terminal protein, may be an important
component of Lewy bodies in Parkinson's disease, dementia with Lewy bodies, and
other neurodegenerative diseases. Additionally, recent genetic studies based on
linkage analysis and cosegregation of A53T and A30P missense mutations
demonstrated that the alpha-synuclein gene may be responsible for the development
of at least some cases of familial Parkinson's disease. Despite intense interest
in the members of the synuclein family, their function(s) and exact role in the
diseases remained unknown. Here we describe a new member of the synuclein family,
which we term synoretin, and show that it is expressed in different retinal
cells, as well as in the brain, and it may affect the regulation of signal
transduction through activation of the Elk1 pathway.
PMID- 10192769
TI - Distinct structures and functions of related pre- and postsynaptic carbohydrates
at the mammalian neuromuscular junction.
AB - Carbohydrates that terminate in beta-linked N-acetylgalactosamine (betaGalNAc)
residues are concentrated in the postsynaptic apparatus of the skeletal
neuromuscular junction and have been implicated in the differentiation of the
postsynaptic membrane. We now report that distinct synapse-specific betaGalNAc
containing carbohydrates are associated with motor nerve terminals. Two
monoclonal antibodies that recognize distinct betaGalNAc-containing epitopes, CT1
and CT2, both stain synaptic sites on skeletal muscle fibers. However, CT1
selectively stains nerve terminal, whereas CT2 selectively stains the
postsynaptic apparatus. Likewise, CT1 and CT2 selectively stain motoneuron-like
and muscle cell lines, respectively. Using the cell lines, we identify distinct
CT1- and CT2-reactive glycolipids and glycoproteins. Finally, we show that GalNAc
modulates the adhesion of motoneuron-like cells to recombinant fragments of a
synaptic cleft component, laminin beta2. Together, these results show that pre-
as well as postsynaptic membranes bear and are affected by distinct but related
synapse-specific carbohydrates.
PMID- 10192770
TI - Application of a rapid method (targeted display) for the identification of
differentially expressed mRNAs following NGF-induced neuronal differentiation in
PC12 cells.
AB - Nerve growth factor (NGF)-induced differentiation of the rat pheochromocytoma,
PC12, cell line presents a model system for the study of early gene expression
changes involved in neuronal differentiation. Rapid alterations in mRNA
expression patterns were investigated in PC12 cells following exposure to NGF
using a set of statistically designed primers that exhibit coding-strand bias,
and the products were analyzed on agarose gels. This simple and rapid method
(targeted display) generated reproducible expression profiles, indicating a
complex pattern of gene regulation, and resulted in the identification of a
number of NGF-regulated transcripts. Thirty-two of these were selected at random
and sequenced, revealing 19 known and 13 novel genes (or ESTs). Northern blot
analysis and RT-PCR confirmed the differential regulation of 22 genes (16 known,
6 novel) and demonstrated 1 false positive result. Antisense application of one
isolated gene product, the serine/threonine kinase MARK1, prevented neuronal
differentiation in transiently transfected PC12 cells.
PMID- 10192771
TI - Muscle structure and innervation are affected by loss of Dorsal in the fruit fly,
Drosophila melanogaster.
AB - In Drosophila, the Rel-protein Dorsal and its inhibitor, Cactus, act in signal
transduction pathways that control the establishment of dorsoventral polarity
during embryogenesis and the immune response during postembryonic life. Here we
present data indicating that Dorsal is also involved in the control of
development and maintenance of innervation in somatic muscles. Dorsal and Cactus
are colocalized in all somatic muscles during postembryonic development. In
larvae and adults, these proteins are distributed at low levels in the cytoplasm
and nuclei and at much higher levels in the postsynaptic component of
glutamatergic neuromuscular junctions. Absence of Dorsal, in homozygous dorsal
mutant larvae results in muscle misinsertions, duplications, nuclear hypotrophy,
disorganization of actin bundles, and altered subcellular distribution of Cactus.
Some muscles show very abnormal neuromuscular junctions, and some motor axon
terminals are transformed into growth cone-like structures embedded in
synaptotagmin-enriched vesicles. The detailed phenotype suggests a role of Dorsal
signalling in the maintenance and plasticity of the NMJ.
PMID- 10192772
TI - Expression of the gene encoding the chemorepellent semaphorin III is induced in
the fibroblast component of neural scar tissue formed following injuries of adult
but not neonatal CNS.
AB - This study evaluates the expression of the chemorepellent semaphorin III
(D)/collapsin-1 (sema III) following lesions to the rat CNS. Scar tissue, formed
after penetrating injuries to the lateral olfactory tract (LOT), cortex,
perforant pathway, and spinal cord, contained numerous spindle-shaped cells
expressing high levels of sema III mRNA. The properties of these cells were
investigated in detail in the lesioned LOT. Most sema III mRNA-positive cells
were located in the core of the scar and expressed proteins characteristic for
fibroblast-like cells. Neuropilin-1, a sema III receptor, was expressed in
injured neurons with projections to the lesion site, in a subpopulation of scar
associated cells and in blood vessels around the scar. In contrast to lesions
made in the mature CNS, LOT transection in neonates did not induce sema III mRNA
expression within cells in the lesion and was followed by vigorous axonal
regeneration. The concomitant expression of sema III and its receptor neuropilin
1 in the scar suggests that sema III/neuropilin-1-mediated mechanisms are
involved in CNS scar formation. The expression of the secreted chemorepellent
sema III following CNS injury provides the first evidence that chemorepulsive
semaphorins may contribute to the inhibitory effects exerted by scars on the
outgrowth of injured CNS neurites. The vigorous regrowth of injured axons in the
absence of sema III following early neonatal lesions is consistent with this
notion. The inactivation of sema III in scar tissue by either antibody
perturbation or by genetic or pharmacological intervention could be a powerful
means to promote long-distance regeneration in the adult CNS.
PMID- 10192773
TI - Apoptosis in neuronal development and transplantation: role of caspases and
trophic factors.
AB - Fetal ventral mesencephalic (VM) transplants have been studied in the context of
dopaminergic (DA) replacement therapy for Parkinson's disease (PD). DA neurons
from VM transplants will grow axons and form functional synapses in the adult
host central nervous system (CNS). Recently, studies have demonstrated that most
of the transplanted DA neurons die in grafts within the first week after
implantation. An important feature of neural development, also in transplanted
developing fetal neural tissue, is cell death. However, while about 50% of cells
born in the CNS will die naturally, up to 99% of fetal cells die after neural
transplantation. It has been shown that VM grafts contain many apoptotic cells
even at 14 days after transplantation. The interleukin-1beta converting enzyme
(ICE) cysteine protease and 11 other ICE-like-related proteases have been
identified, now named caspases. Activation of caspases is one of the final steps
before a neuron is committed to die by apoptosis. Here we review this cell death
process in detail: Since the growth of fetal neural grafts placed in the adult
brain in many ways mimics normal development, it is likely that the caspases also
play a functional role in transplants. Pharmacological inhibitors of caspases and
genetically modified mice are now available for the study of neuronal death in
fetal neuronal transplants. Understanding cell death mechanisms involved in acute
cellular injury, necrosis, and programmed cell death (PCD) is useful in improving
future neuronal transplantation methodology, as well as in neuroprotection, for
patients with neurodegenerative diseases.
PMID- 10192774
TI - The effects of gap junction blockage on neuronal differentiation of human
NTera2/clone D1 cells.
AB - Gap junctions are intercellular channels which provide for the passage of small
ions and molecules (MW <1200 D) among adjacent cells. The NTera2/clone D1
(NT2/D1) cells are CNS precursors which differentiate into NT2-N neurons upon
treatment with retinoic acid (RA) and antiproliferative agents. In this study,
the effects of gap junction blockers 18 alpha-glycyrrhetinic acid (GRA) and
carbenoxolone (CBX) have been compared with those of oleanolic acid (OLA) and
glycyrrhizic acid (GZA), GRA analogs with no blocking effects. Both control and
experimental cultures showed reduction of Cx43 protein after 4 weeks of RA
induction. A major reduction was also observed in expression of cytokeratin,
vimentin, and nestin in control cells at this time point while the cultures
treated with the blockers did not show any significant change. The average number
of MAP2-positive NT2-N differentiated neurons per field of view in the cultures
treated with the blockers was less than 7% of that of control cultures. NT2-N
cells were negative for Cx43, cytokeratin, vimentin, and nestin. The blockers did
not appear to be operating through inhibition of RA signaling, as their presence
did not affect the expression of retinoic acid receptors (RARalpha and RARgamma)
nor did they inhibit RA-mediated gene transcription. These results, together,
show that the blockage of gap junctions interferes with neuronal differentiation
of NT2/D1 cells.
PMID- 10192775
TI - Cerebral astrocyte response to micromachined silicon implants.
AB - The treatment of neurologic disorders and the restoration of lost function due to
trauma by neuroprosthetic devices has been pursued for over 20 years. The
methodology for fabricating miniature devices with sophisticated electronic
functions to interface with nervous system tissue is available, having been well
established by the integrated circuit industry. Unfortunately, the effectiveness
of these devices is severely limited by the tissue reaction to the insertion and
continuous presence of the implant, a foreign object. This study was designed to
document the response of reactive astrocytes in the hope that this information
will be useful in specifying new fabrication technologies and devices capable of
prolonged functioning in the brain. Model probes fabricated from single crystal
silicon wafers were implanted into the cerebral cortices of rats. The probes had
a 1 x 1-mm tab, for handling, and a 2-mm-long shaft with a trapezoidal cross
section (200-microm base, 60microm width at the top, and 130 microm height). The
tissue response was studied by light and scanning electron microscopy at
postinsertion times ranging from 2 to 12 weeks. A continuous sheath of cells was
found to surround the insertion site in all tissue studied and was well developed
but loosely organized at 2 weeks. By 6 and 12 weeks, the sheath was highly
compacted and continuous, isolating the probe from the brain. At 2 and 4 weeks,
the sheath was disrupted when the probe was removed from the fixed tissue,
indicating that cells attached more strongly to the surface of the probe than to
the nearby tissue. The later times showed much less disruption. Scanning electron
microscopy of the probes showed adherent cells or cell fragments at all time
points. Thus, as the sheath became compact, the cells on the probe and the cells
in the sheath had decreased adhesion to each other. Immunocytochemistry
demonstrated that the sheath was labeled with antibodies to glial fibrillary
acidic protein (GFAP), an indicator for reactive gliosis. The tissue surrounding
the insertion site showed an increased number of GFAP-positive cells which tended
to return to control levels as a function of time after probe insertion. It was
concluded that reactive gliosis is an important part of the process forming the
cellular sheath. Further, the continuous presence of the probe appears to result
in a sustained response that produces and maintains a compact sheath, at least
partially composed of reactive glia, which isolates the probe from the brain.
PMID- 10192776
TI - The inflammatory reaction following 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine
intoxication in mouse.
AB - In degenerative disorders of the CNS an immune system involvement in the
pathological process is postulated. The MPTP model of Parkinson's disease seem to
be a good model for studying an inflammation following toxic neurodegeneration.
In this model, microglial and astroglial reactions were previously found around
impaired neurons. In the present work we showed an immune reaction, including
lymphocytic infiltration of CD4+ and CD8+ T cells in the substantia nigra and
striatum and elevated MHC class I and II antigens expression on microglia. Many
activated lymphocytes were present, showing increased LFA-1 and CD44 antigen
expression. We found also that ICAM-1 expression increased on the endothelium and
appeared on microglia in the injured regions. Treatment with dexamethasone
inhibited T-cell infiltration and MHC class II expression, lessened the glial
reaction, and also diminished neuronal impairment. These findings suggest that an
immune mechanism may contribute to the neuronal damage following MPTP
administration.
PMID- 10192777
TI - Diethyldithiocarbamate causes nigral cell loss and dopamine depletion with
nontoxic doses of MPTP.
AB - Although nontoxic when administered alone, diethyldithiocarbamate (DDC) is known
to enhance the dopamine-depleting effects of 1-methyl-4-phenyl-1,2,3,6
tetrahydropyridine (MPTP) in the mouse striatum. The purpose of the present study
was twofold: (i) to carefully characterize the effects of DDC on MPTP-induced
degeneration of dopaminergic neurons in substantia nigra pars compacta using
unbiased, stereological cell counting techniques and (ii) to determine whether or
not DDC can convert a nontoxic dose of MPTP into one which is clearly toxic on
dopaminergic neurons in the substantia nigra. A single low dose of MPTP (15 mg/kg
intraperitoneally (ip)) was used for these studies, which failed to induce any
neurochemical or histological effects on the nigrostriatal system of C57BL/6 mice
when administered alone. However, when animals were pretreated with DDC (400
mg/kg ip), the same dose of MPTP resulted in a 50% loss of neurons in the
substantia nigra pars compacta, as well as a 70% reduction in striatal dopamine
(DA). A 31% reduction of DA in the ventral mesencephalon was also seen. This
combined regimen of DDC and MPTP was not significantly different from a maximally
tolerated "toxic" dose of MPTP alone (15 mg/kg x 4, 1 h apart, ip). As expected,
animals receiving DDC alone did not show any dopamine depletion nor nigral
neuronal loss. The present study confirms previous work suggesting that DDC
enhances MPTP-induced nigral cell loss and shows for the first time that DDC can
"unmask" MPTP toxicity. These observations could have implications for theories
on the cause of Parkinson's disease.
PMID- 10192778
TI - Isolation and cloning of multipotential stem cells from the embryonic human CNS
and establishment of transplantable human neural stem cell lines by epigenetic
stimulation.
AB - Stem cells that can give rise to neurons, astroglia, and oligodendroglia have
been found in the developing and adult central nervous system (CNS) of rodents.
Yet, their existence within the human brain has not been documented, and the
isolation and characterization of multipotent embryonic human neural stem cells
have proven difficult to accomplish. We show that the developing human CNS
embodies multipotent precursors that differ from their murine counterpart in that
they require simultaneous, synergistic stimulation by both epidermal and
fibroblast growth factor-2 to exhibit critical stem cell characteristics. Clonal
analysis demonstrates that human C NS stem cells are multipotent and
differentiate spontaneously into neurons, astrocytes, and oligodendrocytes when
growth factors are removed. Subcloning and population analysis show their
extensive self-renewal capacity and functional stability, their ability to
maintain a steady growth profile, their multipotency, and a constant potential
for neuronal differentiation for more than 2 years. The neurons generated by
human stem cells over this period of time are electrophysiologically active.
These cells are also cryopreservable. Finally, we demonstrate that the neuronal
and glial progeny of long-term cultured human CNS stem cells can effectively
survive transplantation into the lesioned striatum of adult rats. Tumor formation
is not observed, even in immunodeficient hosts. Hence, as a consequence of their
inherent biology, human CNS stem cells can establish stable, transplantable cell
lines by epigenetic stimulation. These lines represent a renewable source of
neurons and glia and may significantly facilitate research on human neurogenesis
and the development of clinical neural transplantation.
PMID- 10192779
TI - Morphological deficits in noradrenergic neurons in GEPR-9s stem from
abnormalities in both the locus coeruleus and its target tissues.
AB - The epileptic condition of the genetically epilepsy-prone rat (GEPR) appears to
be caused partially by deficiencies in the locus coeruleus (LC) innervation of
the superior colliculus (SC). Previous studies provide quantitative documentation
of noradrenergic morphological deficits in the moderately epileptic GEPR-3. The
present findings extend these studies by applying cell culture methodology to
assessments of the severely epileptic GEPR-9. Our data show that total neurite
length, the number of neurite branch points per cell, the cross-sectional area of
cell bodies, and the cell perimeter are deficient in noradrenergic neurons in LC
+ SC cocultures derived exclusively from GEPR-9s compared to analogous cocultures
obtained solely from nonepileptic control rats. Partial restoration of LC neuron
morphology toward normal occurs when the GEPR-9 SC component of the coculture is
replaced with nonepileptic control SC. Finally, when the GEPR-9 SC is cocultured
with the control LC, a partial morphological deficit occurs in the otherwise
normal noradrenergic neurons. However, the magnitude of this deficit is less than
that observed in noradrenergic neurons of the GEPR-9 LC cocultured with the
control SC. These data support the hypothesis that the developmental deficiencies
of noradrenergic neurons of the GEPR-9 are derived from two sources, the LC and
its target tissue, in this case, the SC. Also, intrinsic abnormalities of the LC
appear to make a more pronounced contribution to the noradrenergic deficits than
do those which reside in the SC.
PMID- 10192780
TI - Huntington's disease intranuclear inclusions contain truncated, ubiquitinated
huntingtin protein.
AB - Intranuclear inclusion bodies are a shared pathological feature of Huntington's
disease (HD) and its transgenic mouse model. Using a panel of antibodies spanning
the entire huntingtin molecule, we have investigated the pattern of
immunoreactivity within the intranuclear inclusions in the frontal cortex and
striatum of patients with HD. The intranuclear inclusions reacted with anti
ubiquitin and antibodies against the N-terminal portion of huntingtin (CAG53b,
HP1), but not with HD1 and the 1C2 antibodies that detect the expanded
polyglutamine tract nor the more C-terminal antibodies. However, the 1C2, HP1,
CAG53b, and HD1 antibodies detected granular cytoplasmic deposits in cortical and
striatal neurons that also contained intranuclear N-terminal huntingtin
immunoreactivity. These data show a differential intracellular location of
truncated huntingtin in the HD brain. Both the cytoplasmic and the nuclear
aggregates of the protein fragments could be neurotoxic. The frequency of the
cortical intranuclear inclusions correlated with the size of CAG expansion and
was inversely related to the age at onset and death. No such correlations were
detected for the striatum, which most likely reflects a more advanced neuronal
loss accrued by the time of death.
PMID- 10192781
TI - Neurochemical diversity of dystrophic neurites in the early and late stages of
Alzheimer's disease.
AB - We examined the neurochemical and morphological diversity of abnormal neurites
associated with beta-amyloid plaque formation in the early and late stages of
Alzheimer's disease. Preclinical Alzheimer's disease was characterised by the
presence of abnormal neurites containing either neurofilament or chromogranin A
immunoreactivity. All clustered dystrophic neurites in these cases were
associated with beta-amyloid plaques. Neurofilament immunoreactive dystrophic
neurites in preclinical Alzheimer's disease could be further subclassified into
bulb- and ring-like structures, and these abnormal neurites contained both
phosphorylated and dephosphorylated neurofilament epitopes. Dystrophic neurites
in Alzheimer's disease could be subdivided into predominantly neurofilament, tau,
or chromogranin A immunolabeled forms. Some neurofilament immunoreactive neurites
had a core region labeled for tau. The neurofilaments of the dystrophic neurites
in Alzheimer's disease had the same complement of phosphorylation- and
dephosphorylation-dependent epitopes as observed in preclinical cases. Therefore,
an abnormal accumulation of variably phosphorylated neurofilaments represent the
earliest cytoskeletal alteration associated with dystrophic neurite formation.
Furthermore, these data indicate that dystrophic neurites may "mature" through
neurofilament-abundant forms to the neurites containing the profoundly altered
filaments labeled for tau. The precise morphological and neurochemical changes
associated with dystrophic neurite formation suggests that beta-amyloid plaques
are causing physical damage to surrounding axons. The resultant axonal sprouting
and profound cytoskeletal alterations would follow the chronic stimulation of the
stereotypical reaction to such physical trauma.
PMID- 10192782
TI - The effect of a peripheral nerve lesion on calbindin D28k immunoreactivity in the
cervical ventral horn of developing and adult rats.
AB - Expression of calbindin D28k (CB) immunoreactivity by putative Renshaw cells is
substantially downregulated by sciatic motoneuron axotomy in the adult rat. The
present study investigated the effect of median and ulnar nerve lesion at
different ages on ventral horn CB immunoreactivity 7 days after the injury to see
whether similar results were obtained in the cervical cord and during
development. Two major differences were observed. First, axotomy induced CB
immunoreactivity in some motoneurons, confirmed by retrograde labeling of the
injured neurons with fast blue (FB). Observation of fluorescent phagocytic
microglia revealed that some motoneuron death occurred following lesions at
postnatal day 2 (P2) and P7, but not at P21 or P63. A significantly higher
proportion of remaining FB labeled motoneurons expressed CB following lesion at
P2 (mean 33% +/- 7.6 SD) and P7 (30.6% +/- 5.2) than at P28 (14.0% +/- 1.9).
Second, CB expression by putative Renshaw cells was not significantly
downregulated ipsilateral to the lesion. CB immunofluorescent putative Renshaw
cells were counted in sections containing FB labeled motoneurons. No consistent
differences in the numbers of Renshaw cells ipsilateral and contralateral to the
lesion were found at any age. To confirm that these neurons really were Renshaw
cells, the mediators of recurrent inhibition to cholinergic motoneurons, we
employed double-immunofluorescence labeling with confocal microscopy. The group
of CB immunopositive neurons located among the converging ventral roots in the
cervical cord were closely apposed by many axon terminals immunoreactive for (i)
vesicular acetylcholine transporter and (ii) cholera toxin B localized to motor
axon collaterals by injection of this tracer into a distal forelimb muscle. We
conclude that motoneuron axotomy need not always downregulate CB expression in
associated Renshaw cells. In addition, some brachial motoneurons respond to
axotomy by expressing CB.
PMID- 10192783
TI - Functional benefit from clomethiazole treatment after focal cerebral ischemia in
a nonhuman primate species.
AB - Clomethiazole (CMZ) (Zendra) is neuroprotective in rodents following focal and
global ischemia. However, its neuroprotective effects in other species,
particularly on functional outcome, have not been reported. We have therefore
examined the ability of CMZ to ameliorate the functional deficits produced by a
focal cerebral ischemic lesion in the marmoset, a New World primate. Six monkeys
received permanent middle cerebral artery occlusion (pMCAO); six further monkeys
received pMCAO with administration of CMZ, 5 min after the arterial occlusion, by
intraperitoneal bolus injection and by subcutaneous implantation of an osmotic
minipump, which released CMZ for 24 h. The monkeys were trained and tested
preoperatively on a number of behavioral tasks which were repeated 3 and 9 weeks
after surgery. CMZ-treated monkeys were better than non-drug-treated monkeys at
using the disabled arm contralateral to the lesion and also showed a reduction in
contralateral spatial hemineglect. Postmortem histopathological analysis at
several stereotaxic levels showed a significant reduction in the area of ischemic
damage in CMZ-treated monkeys compared to that in untreated animals. CMZ
treatment reduced the overall volume of damage by 31.8% (MCA group, 370.8 +/-
37.4 mm3 of damage; CMZ group, 253.0 +/- 38.0 mm3 of damage). This study
demonstrates that CMZ is neuroprotective in a nonhuman primate species and is
able to ameliorate the level of functional disability and reduce the size of
infarct produced by focal cerebral ischemia.
PMID- 10192784
TI - BCL-2 transduction, using a herpes simplex virus amplicon, protects hippocampal
neurons from transient global ischemia.
AB - Transient global ischemia results in selective neuronal damage of hippocampal CA1
neurons. Five minutes of bilateral common carotid artery occlusion, in the
Mongolian gerbil, effectively restricts forebrain blood flow, resulting in a
delayed neuronal death of CA1 pyramidal cells. While there is a delay of
approximately 72 h in the appearance of cell death, markers related to the
mechanism of ischemic death become apparent well before neurons die. Ischemia
induced increases in the cell-death-promoting protein, bax, may disrupt the bcl
2/bax ratio necessary for normal neuronal functioning and thus promote transient
ischemic death. In order to locally maintain this critical bcl-2/bax ratio and
thus protect CA1 neurons from delayed neuronal death, a herpes simplex viral
(HSV) vector was used to selectively introduce human bcl-2, under the control of
the herpes IE 4/5 promoter, into the CA1 region of the gerbil hippocampus. Twenty
four hours prior to ischemia surgery, 1 microl of HSVbcl-2 was infused
unilaterally into the CA1 region at a rate of 2 nl/min. Seventy-two hours after
ischemia the animals were sacrificed and processed using Nissl, silver
degeneration, and immunohistochemical (anti-human bcl-2) staining.
Immunohistochemistry demonstrated both glial and neuronal bcl-2 expression around
the HSVbcl-2 infusion site. The evaluation following silver degeneration staining
indicated a further degeneration of CA1 neurons in the immediate area of the
viral vector infusion. This damage seems to be the result of cellular debris
associated with the processing of the viral amplicons. Silver degeneration
staining is not present in the areas that demonstrate bcl-2 staining. These
neurons appear to have been rescued from ischemic damage. This result was
confirmed using the Nissl staining. Therefore, by altering the local ratio of bcl
2/bax using the HSVbcl-2 vector one may protect CA1 pyramidal cell from the
delayed neuronal death of transient global ischemia.
PMID- 10192785
TI - Immunochemical analysis of vesicular monoamine transporter (VMAT2) protein in
Parkinson's disease.
AB - The vesicular monoamine transporter (VMAT2) has been suggested to be an excellent
marker of presynaptic dopaminergic nerve terminals in the striatum of Parkinson's
disease patients based on its high level of expression and insensitivity to drugs
used to treat the disease. Previous in vivo imaging and postmortem binding
studies have detected a loss in striatal VMAT2 binding in Parkinson's diseased
(PD) brain; however, these techniques have poor spatial resolution and may suffer
from nonspecific binding of some ligands. In this study, we use novel polyclonal
antibodies to distinct regions of human VMAT2 to quantify and localize the
protein. Western blot analysis demonstrated marked reductions in VMAT2
immunoreactivity in putamen, caudate, and nucleus accumbens of PD brain compared
to control cases. Immunohistochemistry revealed VMAT2 immunoreactive fibers and
puncta that were dense throughout the striatum of control brains, but which were
drastically reduced in putamen of PD brains. In PD brains the caudate showed a
significant degree of sparing along the border of the lateral ventricle and the
nucleus accumbens was relatively preserved. The distribution of VMAT2 in striatum
and its loss in PD paralleled that of the dopamine transporter (DAT), a
phenotypic marker of dopamine neurons. Thus, immunochemical analysis of VMAT2
protein provides novel and sensitive means for localizing and quantifying VMAT2
protein and nigrostriatal dopamine terminals in PD. Furthermore, the relative
expression of VMAT2 compared to that of DAT may predict the differential
vulnerability of dopamine neurons in PD.
PMID- 10192786
TI - Impaired inflammatory response to glial cell death in genetically metallothionein
I- and -II-deficient mice.
AB - Metallothionein I+II (MT-I+II) are acute-phase proteins which are upregulated
during pathological conditions in the brain. To elucidate the neuropathological
importance of MT-I+II, we have examined MT-I+II-deficient mice following ip
injection with 6-aminonicotinamide (6-AN). 6-AN is antimetabolic and toxic for
bone marrow cells and grey matter astrocytes. In MT+/+ mice, injection with 6-AN
resulted in breakdown of the blood-brain barrier (BBB) and absence of GFAP
positive astrocytes in specific grey matter areas of the brain stem. Reactive
astrocytosis encircled the damaged grey matter areas, which were heavily
infiltrated by microglia/macrophages. The recruitment of hematogenous macrophages
was accompanied by leakage of the BBB. The immunoreactivity (ir) of granulocyte
macrophage-colony-stimulating factor (GM-CSF) and the receptor for GM-CSF (GM
CSFrec) was significantly upregulated in astrocytes and microglia/macrophages,
respectively. MT-I+IIir was also clearly increased in astrocytes surrounding the
damaged areas, while that of the CNS-specific MT isoform, MT-III, was mildly
increased in both astrocytes and microglia/macrophages. In MT-/- mice injected
with 6-AN, the BBB remained almost intact. The damage to specific grey matter
areas was similar to that observed in MT+/+ mice, but reactive astrocytosis,
microglia/macrophages infiltration, and GM-CSFir and GM-CSFrecir were clearly
reduced in MT-/- mice. In contrast, MT-IIIir was dramatically increased in MT-/-
mice. Total zinc decreased and histochemically detectable zinc increased in the
brain stem after 6-AN similarly in MT+/+ and MT-/- mice. Bone marrow myeloid
monocytes and macrophages were increased as a reaction to 6-AN only in MT+/+
mice. The results demonstrate that the capability of MT-/- mice to mount a normal
inflammatory response in the brain is severely attenuated, at least in part
because of 6-AN-induced bone marrow affectation, involving MT-I+II for the first
time as major factors during CNS tissue damage.
PMID- 10192787
TI - Adsorptive endocytosis of HIV-1gp120 by blood-brain barrier is enhanced by
lipopolysaccharide.
AB - Previous work suggests that gp120 mediates the passage of HIV-1 and infected
immune cells across the blood-brain barrier (BBB) by induction of adsorptive
endocytosis (AE) in brain endothelial cells. Other work has suggested that
cytokines may increase the permeability of the BBB to free virus or infected
immune cells. Here, we investigated the ability of lipopolysaccharide (LPS), a
bacterial wall toxin that stimulates the release of cytokines, to increase gp120
passage across the BBB by enhancement of AE and/or induction of BBB disruption.
We found that LPS enhanced the passage of gp120 radioactively labeled with 125I
(I-gp120) in a reversible, time-dependent, prostaglandin-independent manner that
was not completely explained by disruption of the BBB. LPS also enhanced
wheatgerm agglutinin mediated uptake of I-gp120 almost exclusively through the
potentiation of AE. These results show that LPS or cytokines released by LPS can
have a major effect on the permeability of the BBB to HIV-1gp120 both by
stimulating AE and by inducing a disruption of the BBB. This suggests that
bacterial infection or other inflammatory states could facilitate invasion of the
CNS by HIV-1.
PMID- 10192788
TI - The use of single phrenic axon recordings to assess diaphragm recovery after
cervical spinal cord injury.
AB - Electrophysiological recordings taken from the whole phrenic nerve have been
utilized previously to describe the gradual increase in functional recovery of a
hemidiaphragm paralyzed by ipsilateral C2 hemisection during the crossed phrenic
phenomenon (CPP). Although the increase in activity has been temporally
correlated with hemisection-induced morphological alterations of the phrenic
nucleus, suggesting an association of the increased activity with the
morphological alterations, whole phrenic nerve recordings during the CPP can
provide only limited information. The purpose of the present study, therefore,
was to use phrenic single-axon recording techniques to better understand the
mechanisms underlying the recovery of respiratory activity during the expression
of the CPP. Recordings from the whole phrenic nerve on the right side and from
small fascicles of the phrenic nerve that show only the activity of single
phrenic axons (units) on the left side were made in the neck before left spinal
hemisection and during the CPP. The results indicated that there were two types
of units firing before and during the CPP: an early- and a late-firing unit based
on the time of their firing onset in relation to whole phrenic nerve activity.
Ten early units and 25 late units were identified according to the shape of their
spikes before hemisection as well as during the CPP. In addition to these units,
20 new units were recruited during CPP activity. These new units were mainly of
the late-onset type. The results also indicated that there was a significant
increase in the frequency of firing of both early and late units. The results
specifically indicate therefore that the increase in respiratory activity
recorded previously in the whole phrenic nerve during the CPP is most likely due
to: (i) an increase in firing frequency for both early- and late-firing units and
(ii) a recruitment of predominantly late-firing units into the CPP response.
These results are important in understanding more completely the mechanisms that
can facilitate recovery of the diaphragm after spinal cord injury.
PMID- 10192790
TI - Comparing deficits following excitotoxic and contusion injuries in the thoracic
and lumbar spinal cord of the adult rat.
AB - The majority of human spinal cord injuries involve gray matter loss from the
cervical or lumbar enlargements. However, the deficits that arise from gray
matter damage are largely masked by the severe deficits due to associated white
matter damage. We have developed a model to examine gray matter-specific deficits
and therapeutic strategies that uses intraspinal injections of the excitotoxin
kainic acid into the T9 and L2 regions of the spinal cord. The resulting deficits
have been compared to those from standard contusion injuries at the same levels.
Injuries were assessed histologically and functional deficits were determined
using the Basso, Beattie, and Bresnahan (BBB) 21-point open field locomotor scale
and transcranial magnetic motor evoked potentials (tcMMEPs). Kainic acid
injections into T9 resulted in substantial gray matter damage; however, BBB
scores and tcMMEP response latencies were not different from those of controls.
In contrast, kainic acid injections into L2 resulted in paraplegia with BBB
scores similar to those following contusion injuries at either T9 or L2, without
affecting tcMMEP response latencies. These observations demonstrate that gray
matter loss can result in significant functional deficits, including paraplegia,
in the absence of a disruption of major descending pathways.
PMID- 10192789
TI - Striatal grafts in a rat model of Huntington's disease: time course comparison of
MRI and histology.
AB - Survival and integration into the host brain of grafted tissue are crucial
factors in neurotransplantation approaches. The present study explored the
feasibility of using a clinical MR scanner to study striatal graft development in
a rat model of Huntington's disease. Rat fetal lateral ganglionic eminences grown
as free-floating roller-tube cultures were grafted into the quinolinic acid
lesioned striatum, and T1- and T2-weighted sequences were acquired at 2, 7, 21,
and 99 days posttransplantation. MR images were then compared with images of
corresponding histological sections. The lesion-induced striatal degeneration
caused a progressive ventricle enlargement, which was significantly different
from controls at 21 days posttransplantation. Seven days posttransplantation, T1
weighted images revealed a defined liquid-isointense signal surrounded by a
hyperintense rim at the site of graft placement, which was found unaltered for
the first 21 days posttransplantation, whereas a hypointense graft signal was
detected at 99 days posttransplantation. At 2 days posttransplantation, T2
weighted images showed the graft region as a hyperintense area surrounded by a
rim of low signal intensity but at later time-points graft location could not be
further verified. Measures for graft size and ventricle size obtained from MR
images highly correlated with measures obtained from histologically processed
sections (R = 0.8, P < 0.001). In conclusion, the present study shows that fetal
rat lateral ganglionic eminences grown as free-floating roller-tube cultures can
be successfully grafted in a rat Huntington model and that a clinical MR scanner
offers a useful noninvasive tool for studying striatal graft development.
PMID- 10192791
TI - Addition of fresh blood to intrastriatal grafts of embryonic mesencephalon into
the hemiparkinsonian rat does not impair the survival of grafted dopaminergic
neurones.
AB - Cell transplantation therapy for Parkinson's patients, although seen to bring
benefit to some patients during first clinical trials, remains impracticable on a
large scale, in part because of the poor survival of the dopaminergic neurones
transplanted. The loss of dopaminergic neurones occurs rapidly over the first 1-2
days after transplantation, in response to factors intrinsic to the host brain.
Here we investigated whether contamination of the grafted cell suspension with
blood during the transplantation procedure may be one factor responsible for the
poor survival of DA neurons within the graft, possibly through factors such as
free iron or complement. 6-Hydroxydopamine lesioned rats were grafted with 2
microl suspension of dissociated E14 ventral mesencephalon to which 1 microl
blood or 1 microl grafting medium was added. After 6 weeks, there was no
significant difference in the number of surviving DA neurones in the two groups.
We conclude that contamination of grafts with blood is not a major factor
responsible for the extensive death of dopaminergic neurones within them.
PMID- 10192792
TI - Electrophysiological and clinical desensitization to apomorphine administration
in parkinsonian patients undergoing stereotaxic neurosurgery.
AB - A decreased motor response after repeated doses of apomorphine is observed in
severely affected Parkinson's disease patients. We simultaneously studied
clinical symptoms and internal pallidus single unit activity in three
parkinsonian patients underlying stereotaxic neurosurgery for deep brain
stimulation. In each patient, two closely spaced doses of intraoperatory
apomorphine were administered, while recording the same extracellular unit. The
reduced clinical effect of the second administration was correlated to a lessened
inhibition of the pallidal single unit recorded throughout the double
administration. Our data support the proposition that fast postsynaptic
desensitization to dopamine agonists may take place in the basal ganglia nuclei
and play a role in the physiopathology of levodopa long-term treatment syndrome.
PMID- 10192793
TI - Reelin, the extracellular matrix protein deficient in reeler mutant mice, is
processed by a metalloproteinase.
AB - Reelin is the extracellular protein defective in reeler mice. It is believed that
reelin acts via the extracellular matrix to influence the development of nearby
neurons, but the mechanism remains thus far unknown. In the present work, we
present in vivo and in vitro evidence that reelin is cleaved. This processing did
not occur in Relnrl-Orl mutant mice in which reelin is not secreted and was
prevented in explant cultures by brefeldin treatment, suggesting that it takes
place extracellularly or in a postendoplasmic reticulum compartment. Reelin
cleavage was inhibited by zinc chelators known to inhibit metalloproteinases but
was unaffected by inhibitors of serine, cysteine, or aspartate proteinases.
Furthermore, reelin cleavage was insensitive to inhibitors of matrixins,
neprilysin, meprin, and peptidyl dipeptidase A, suggesting that the processing
enzyme belongs to a different enzyme family. This enzyme and the physiological
meaning of reelin processing remain to be characterized further.
PMID- 10192795
TI - Announcement
PMID- 10192794
TI - Induction of Eph B3 after spinal cord injury.
AB - Spinal cord injury (SCI) in adult rats initiates a cascade of events producing a
nonpermissive environment for axonal regeneration. This nonfavorable environment
could be due to the expression of repulsive factors. The Eph receptor protein
tyrosine kinases and their respective ligands (ephrins) are families of molecules
that play a major role in axonal pathfinding and target recognition during
central nervous system (CNS) development. Their mechanism of action is mediated
by repellent forces between receptor and ligand. The possible role that these
molecules play after CNS trauma is unknown. We hypothesized that an increase in
the expression of Eph proteins and/or ephrins may be one of the molecular cues
that restrict axonal regeneration after SCI. Rats received a contusive SCI at T10
and in situ hybridization studies 7 days posttrauma demonstrated: (i) a marked up
regulation of Eph B3 mRNA in cells located in the white matter at the lesion
epicenter, but not rostral or caudal to the injury site, and (ii) an increase in
Eph B3 mRNA in neurons in the ventral horn and intermediate zone of the gray
matter, rostral and caudal to the lesion. Immunohistochemical analyses localizing
Eph B3 protein were consistent with the mRNA results. Colocalization studies
performed in injured animals demonstrated increased Eph B3 expression in white
matter astrocytes and motor neurons of the gray matter. These results suggest
that Eph B3 may contribute to the unfavorable environment for axonal regeneration
after SCI.
PMID- 10192797
TI - Interphotoreceptor retinoid-binding protein (IRBP) is rapidly cleared from the
Xenopus interphotoreceptor matrix.
AB - The interphotoreceptor matrix (IPM) is a highly-organized extracellular matrix
critical to retinal development and function. Although the concentrations of its
components are carefully regulated, little is known about the mechanisms of this
regulation. Interphotoreceptor retinoid-binding protein (IRBP) is the most
abundant soluble protein component of the IPM. Although its rate of clearance is
thought to be an important factor regulating the concentration of IRBP within the
IPM, no study has measured the rate of its extracellular turnover. Here we
determine the rate of turnover of matrix IRBP in Xenopus. The rate of IRBP
turnover was estimated by measuring the loss of radioactivity from protein
labeled by a single injection of a radiolabeled protein precursor. To provide an
estimate of the rate of IRBP turnover, we have examined the following issues: (1)
Quantitative extraction of IRBP from the IPM for biochemical analysis. (2) Routes
of delivery of radiolabeled precursor to achieve a pulse label in vivo. (3)
Selection of labeled precursor in order to minimize reutilization of radiolabel.
Using Western blot analysis, immunoprecipitation and immuno-electron microscopy,
we found that IRBP can be quantitatively extracted from the IPM by a simple
saline wash. IRBP was radiolabeled by systemic or intravitreal injection of
either [35S]methionine or carboxyl-terminal labeled [1-14C]leucine. The specific
activity of matrix IRBP was determined by either phosphorimaging or fluorography
of Coomassie blue-stained SDS-polyacrylamide gels. Intravitreal injection of
tracer was more effective than systemic delivery in achieving a pulse of
radiolabel to the retina. This may be due to intravitreal injection allowing the
body to act as a 'sink' for radiolabeled amino acid. When radiolabeled precursor
was delivered by intravitreal injection, the calculated half-life of matrix IRBP
using [35S]methionine was 25. 6+/-0.82 hr; in contrast, it was 10.7+/-2.9 hr
using [1-14C]leucine. The faster apparent IRBP turnover using [1-14C]leucine is
interpreted in context of the early decarboxylation of leucine during its
degradation. Our results demonstrate rapid turnover of IRBP in the Xenopus IPM in
vivo and suggest that the IPM is a dynamic structure undergoing continuous
renewal.
PMID- 10192796
TI - Expression of HGF, KGF, EGF and receptor messenger RNAs following corneal
epithelial wounding.
AB - Hepatocyte growth factor (HGF), keratinocyte growth factor (KGF), epidermal
growth factor (EGF), and their receptors have been associated with homeostasis
and wound healing in the cornea. The purpose of this study was to examine the
expression of the messenger RNAs for these growth factors and receptors in a
wounded series of mouse corneas using in situ hybridization. In situ
hybridization was performed with 3H-labeled riboprobes on unwounded corneas and
corneas at 30 minutes, 4, 12, 24, 48 and 72 hr, and 7 days after epithelial
scrape wounds in Balb/C mice. Qualitative and semi-quantitative analyses were
performed. Expression of HGF, KGF and EGF mRNAs in keratocytes in the unwounded
cornea was low. EGF mRNA was also expressed in unwounded corneal epithelium.
Following wounding, however, these growth factor mRNAs were markedly upregulated
in keratocytes. EGF mRNA expression in the epithelium appeared unaffected by
wounding. At seven days after wounding and several days following closure of the
epithelial defect, HGF mRNA and KGF mRNA were still expressed at higher levels in
keratocytes compared with unwounded corneas. No difference in expression of HGF
or KGF mRNAs between limbal, peripheral corneal, or central corneal keratocytes
was noted in the unwounded cornea, KGF receptor mRNA was prominently expressed
throughout the unwounded corneal epithelium. HGF receptor mRNA and EGF receptor
mRNAs were expressed at low levels in unwounded cornea epithelium. Following
scrape injury, expression of HGF receptor mRNA and KGF receptor mRNA were
markedly upregulated in the corneal epithelium, while no significant increase in
EGF receptor mRNA expression was noted. These studies suggest a prominent role
for HGF and KGF in modulating corneal epithelial wound healing following injury.
Less prominent changes in EGF mRNA and EGF receptor mRNA in the corneal
epithelium following wounding may suggest that EGF has more of a role in
homeostasis in the mouse corneal epithelium.
PMID- 10192798
TI - The acinar and ductal organisation of the tarsal accessory lacrimal gland of
Wolfring in rabbit eyelid.
AB - The purpose of this study was to objectively assess the tarsal accessory lacrimal
gland of Wolfring and its excretory duct by transmission electron microscopy
(TEM). The upper eyelid of 6 female grey rabbits (2 kg) was fixed in the fully
extended configuration with buffered glutaraldehyde. At the tarsal/orbital
portion of the palpebral conjunctiva, a series of prominent acinar glands were
located by both light microscopy and TEM. Cells within the acini were
characterised by apical tight junctions and desmosomal connections as well as
abundant intra-cytoplasmic osmophillic (secretory) granules. The apical surfaces
were profusely decorated with microvilli-like extensions. In the vicinity of the
acini, and traversing over several millimetres of adjacent sub-epithelial
parenchyma and epithelium, was an extensive system of duct-like spaces lined with
secretory cells decorated with microvilli. These ducts run a tortuous course
within the palpebral conjunctival epithelium leading to crypt-like termination's
along the eyelid inner surface. The tarsal accessory lacrimal gland of Wolfring
thus has an acinar structure similar to the main lacrimal glands, and its ducts
are lined by secretory cells along the entire tortuous course towards the
palpebral conjunctival surface, where the ducts emerge at multiple points at the
tarsal/orbital portion of the surface.
PMID- 10192799
TI - Retinal pigment epithelial cells are heterogeneous in their expression of MHC-II
after stimulation with interferon-gamma.
AB - The pattern of interferon-gamma-induced major histocompatibility complex Class II
antigen expression was evaluated on the retinal pigment epithelium. Experiments
were performed in vitro using explant cultures of aged and fetal human eyes and
in vivo in albino rabbits. The human explants were stimulated with 50 U ml-1
interferon-gamma for 3 days prior to immunostaining for Class II. The rabbit eyes
were subretinally injected in vivo with 50 microl of interferon-gamma (500 U ml
1) and analyzed immunohistochemically 3 days later. A heterogeneous pattern of
Class II expression was present in the interferon-gamma-stimulated retinal
pigment epithelial cells, in both the in vivo and the in vitro experiments. In
aged human eyes the percent of Class-II positive cells was higher in the
periphery than in the posterior pole (macular region) after interferon-gamma
stimulation (P<0.01). No such difference was found in the fetal eyes. These data
demonstrate that retinal pigment epithelial cells are heterogeneous in their
response to interferon-gamma. The results are supportive of previous studies
demonstrating the structural and proliferative heterogeneity of the retinal
pigment epithelium. Together, these studies provide support for the possibility
of functional retinal pigment epithelial heterogeneity.
PMID- 10192800
TI - Plasma membrane disruption underlies injury of the corneal endothelium by
ultrasound.
AB - The nature and the extent of acute injury to corneal endothelial cells caused by
exposure to ultrasound radiation were characterized, as well as the long-term
reaction of these cells to this form of injury. It was found that the degree of
lethal cell injury induced by ultrasound scaled with exposure intensity and
duration. Immediate changes in plasma membrane permeability were induced by
ultrasound exposure. This ultrasound-induced permeability change was, however,
transient in many cells, allowing them to trap and retain a normally impermeant
tracer, fluorescein dextran, in cytosol. Microvilli were present on ultrasound
treated cells in far greater density than on control cells, characteristic of
exocytosis-based resealing. Cultures containing a majority of transiently
permeabilized endothelial cells were morphologically indistinguishable from
untreated control cultures, and the fluorescein dextran-labeled cells in these
populations locomoted and divided normally. We conclude that cell death due to
ultrasound exposure can occur rapidly via a necrotic mechanism that can be
attributed to mechanically induced damage to the plasma membrane. However, not
all cells injured become necrotic: some survive and appear to behave normally
after exposure. Conditions that favor plasma membrane disruption resealing, e.g.
that result in sub-lethal rather than lethal cell injury, may mitigate the
reduction in corneal endothelial cell density consequent on phacoemulsification
and aspiration surgery.
PMID- 10192801
TI - Effects of topical epinephrine on aqueous humor dynamics in the cat.
AB - The purpose of this study was to investigate, in cats, the effects of topical
epinephrine on aqueous humor dynamics as measured by the non-invasive method of
fluorophotometry and by other methods. Measurements were carried out on 12 cats
before and after one week of twice daily treatment with 2% epinephrine
hydrochloride to one eye. Aqueous flow and outflow facility were determined using
fluorophotometry. Uveoscleral outflow was calculated from these results and was
evaluated with anterior chamber perfusion of FITC-dextran. Outflow facility also
was measured by tonography. Epinephrine-treated eyes, compared with their
baseline values, showed a 31% reduction in intraocular pressure (P<0.001), a 23%
reduction in aqueous flow (P<0.05), a 60% increase in fluorophotometric outflow
facility (P<0.05), and a 43% increase in tonographic outflow facility (P<0.05).
Treated eyes, compared with contralateral control eyes, showed a 27% reduction in
IOP (P<0.005), a 25% reduction in aqueous flow (P<0.005), a 38% increase in
fluorophotometric outflow facility (P<0.05), and a 34% increase in tonographic
outflow facility. When evaluated by both fluorophotometry and FITC-dextran tracer
methods, epinephrine had no significant effect on uveoscleral outflow. It was
concluded that, in cats treated with topical epinephrine twice daily for a week,
a reduction in intraocular pressure is induced by an increase in outflow facility
and decrease in aqueous flow.
PMID- 10192802
TI - Lp82 is the dominant form of calpain in young mouse lens.
AB - The purpose of this study was to characterize Lp82 calpain in normal mouse. Lp82
is a lens-specific, calcium-activated isozyme from the calpain super family of
cysteine proteases (EC 34.22.17). RT-PCR and molecular cloning were performed on
total RNA from 12 day-old mice. Lp82 and m-calpain protein levels and proteolytic
activities in lenses were measured by casein zymography, immunoblotting, and
ELISA after partial purification by DEAE-HPLC. The 2334-bp cDNA encoding for
mouse Lp82 contained a single large open reading frame encoding a protein of 709
amino acid residues with a calculated molecular weight of 82.2 kDa and a
predicted pI of 5.8. The amino acid sequence of mouse lens Lp82 was 99%
homologous to rat lens Lp82. As in rat, mouse lens Lp82 showed a unique N
terminus and deletion of the IS1 and IS2 regions. In contrast to rat, Lp82 was
the dominant calpain in young mouse lens. Lp82 was lens-specific, and the lens
nucleus contained the highest specific activity of Lp82 and very little m
calpain. Endogenous Lp82 in lens soluble proteins was activated by addition of
calcium and caused limited proteolysis of crystallins even in the presence of
large amounts of recombinant domain I from the natural calpain inhibitor
calpastatin. Loss of Lp82 protein accompanied aging of mouse lens. Lp82 may be
responsible for a major portion of crystallin proteolysis occurring during normal
lens development and maturation, or during cataract formation in young mice.
PMID- 10192803
TI - Cataract formation through the polyol pathway is associated with free radical
production.
AB - The relationship between sugar cataract formation and radical production was
investigated. The in vivo formation of free radicals in the lenses of rats fed on
a diet containing 25% and 50% galactose was studied using the electron spin
resonance (ESR) spin trapping method. Effects of treatment with aldose reductase
inhibitor (ARI) SNK-860 on free radical formation were determined in 25% and 50%
galactose fed rats. Hydroxyl radical (*OH) adduct of the spin trap 5,5'-dimethyl
1-pyrroline- N -oxide (DMPO) was directly detected in the superficial cortical
cataract obtained from 25% and 50% galactose-fed rats. *OH production was
completely inhibited by ARI SNK-860 in both galactose groups. Polyol accumulated
in rat lenses given 50% galactose with a peak within the first 2 weeks, and was
significantly inhibited by SNK-860. The increase in *OH production was considered
with the polyol accumulation in both galactose groups. The dose of SNK-860 to
inhibit *OH by 50% level was estimated at 3 m by the method of kinetic
competition in vitro experiment. SNK-860 is not an effective *OH scavenger
compared to other *OH scavengers. The results of the present study suggest that
*OH is indirectly inhibited by SNK-860 resulting from decreasing polyol and *OH
formation is related to sugar cataract formation in early stages, possibly via
the Fenton reaction involving H2O2 produced from the activated polyol pathway. We
suppose that *OH may accelerate damage to the cell membrane of lens fibers
resulting from polyol accumulation *OH may play an important role in the early
stage of sugar cataract process.
PMID- 10192804
TI - Detailed localization of photoreceptor guanylate cyclase activating protein-1 and
-2 in mammalian retinas using light and electron microscopy.
AB - Guanylate cyclase activating proteins, GCAP-1 and GCAP-2, have a pivotal role in
the activation of guanylate cyclase in phototransduction. Previous studies on the
localization of GCAP-1 and GCAP-2 are contradictory. In this study, we tried to
avoid possible artifacts accompanied by immunocytochemistry. Immunolabeling of a
GCAP was carried out using antibodies pre-adsorbed with a different type of GCAP.
In addition, immunolabeling was performed using three different animal species
under different fixation and embedding. Electron microscopic immunocytochemistry
was also performed to reveal subcellular localization of GCAPs as well as
confirming data obtained by light microscopy. All data indicate that anti-GCAP-1
antibody binding sites were found predominantly in cone outer segments, in
particular, in disk membrane regions. Sparse labeling was observed in rod outer
segments, but the labeling was much lower than that seen in cone outer segments.
Less labeling is also found in synaptic regions and inner segments of cones. No
labeling was detected in connecting cilia and its cytoplasmic extensions. Such
labeling patterns were similar among human, monkey and bovine retinas. The
localization of GCAP-1 is consistent with the pattern of a recently reported
human cone-specific degeneration. Anti-GCAP-2 antibody binding sites were
detected in both inner and outer segments of rods and cones of all three animals
although the labeling density was slightly different among species. Cryo-immuno
labeling of GCAP-2 in bovine retinas revealed that labeling sites were more
concentrated in rods than those of cones, and that synaptic regions were also
labeled. The different localization of GCAPs suggest that roles of GCAP-1 and
GCAP-2 may be different.
PMID- 10192805
TI - Cultured chicken embryo lens cells resemble differentiating fiber cells in vivo
and contain two kinetic pools of connexin56.
AB - The lens is an avascular organ in which gap junctions play a pivotal role for
cell physiology and transparency. Here we evaluate a lens culture system as a
model for studies of lens gap junction dynamics. In culture, chicken embryo lens
cells initially form a monolayer of epithelial cells. Subsequently, the
epithelial cells differentiate into lentoids, birefringent multicellular
structures composed of fiber-like cells. We examined the cultures for the
expression of cellular markers and lens fiber specific proteins using
immunofluorescence and immunoblot analysis. We also determined the half-life of
connexin56 (Cx56), a fiber-specific gap junction protein. All lens cells in
culture expressed actin, endoplasmic reticulum proteins and N-cadherin. Only
lentoid cells expressed the lens fiber connexins, Cx45.6 and Cx56. Cx56 localized
at appositional membranes and did not co-localize with endoplasmic reticulum
proteins or N-cadherin. Two pools of Cx56 were detected in these cultures, one
with a half-life of a few hours and the other with a half-life of days. The two
pools contained phosphorylated forms of Cx56 of different apparent molecular
weights. These results suggest that lens cells in culture can be used as a model
for the study of lens biology. They also suggest that phosphorylation of Cx56
might be regulating the stability of the protein.
PMID- 10192806
TI - Filling-in after focal loss of photoreceptors in rat retina.
AB - We investigated the fate of isolated photoreceptor lesions in rat retina over a
time span of 6 months. With a carefully selected dose of UV-A (380 nm) a complete
loss of photoreceptors was caused in sharply demarcated areas of 200, 400 or 800
microm wide, without visible damage to other retinal layers. One day after
irradiation, all rods were pyknotic. Three weeks later practically all damaged
photoreceptors were removed. The size of the lesion had decreased as the
surrounding photoreceptors had migrated into the lesion. The outer segment tips
had moved inwards up to 200 microm, but the innermost nuclei in the outer nuclear
layer had moved inwards substantially less. The distance over which the
photoreceptors migrated increased with lesion size, but only 200 microm defects
were filled-in completely on the level of the outer segments. Between three weeks
and six months after irradiation, no further decrease in lesion size occurred. We
conclude that after local loss of photoreceptor cells the bordering
photoreceptors rapidly shift into the lesion area, but complete filling-in is
limited to very small lesions.
PMID- 10192808
TI - Mechanisms underlying the neurogenic relaxation of isolated porcine sphincter
pupillae.
AB - Mechanisms of relaxation induced by nerve stimulation were examined in isolated
porcine iris sphincter muscle in reference to norepinephrine, nitric oxide (NO)
and vasoactive intestinal polypeptide (VIP) and the functional interaction of
inhibitory and excitatory nerves. Changes in isometric tension were recorded in
strips of the sphincter pupillae, which were stimulated by transmurally applied
electrical pulses. The presence of neurons containing acetylcholinesterase and
tyrosine hydroxylase (TH) was determined histochemically. Transmural electrical
stimulation (0.5-20 Hz) produced a frequency-related contraction, which was
reversed to a relaxation by atropine in prostaglandin F2alpha-contracted strips.
The relaxant response was abolished by timolol and suppressed by metoprolol, a
beta1-adrenoceptor antagonist, but was not influenced by butoxamine, a beta2
receptor antagonist. Norepinephrine-induced relaxations were also attenuated only
by timolol and metoprolol. Treatment with NG-nitro-L-arginine, a NO synthase
inhibitor, and [D-p-Cl-Phe6,Leu17]VIP, a VIP receptor antagonist, did not inhibit
the neurogenic relaxation. Contractions induced by nerve stimulation were
potentiated by timolol and physostigmine but not by the NO synthase inhibitor. In
the sphincter muscle, cholinesterase- and TH-positive nerve fibers and bundles
were histologically detected. It is concluded that porcine iris sphincter is
innervated by cholinergic excitatory and adrenergic inhibitory nerves. The
neurogenic relaxation is associated solely with activation of beta1 adrenoceptors
by norepinephrine but is not mediated by NO or VIP.
PMID- 10192807
TI - Hyperbaric oxygen in vivo accelerates the loss of cytoskeletal proteins and MIP26
in guinea pig lens nucleus.
AB - Previous studies have shown that treatment of guinea pigs with hyperbaric oxygen
(HBO) produces certain changes in the lens nuclei of the animals which are
typical of those occurring during aging. These include an increase in nuclear
light scattering (NLS), elevation in levels of oxidized thiols, loss of water
soluble protein and damage to nuclear membranes. The present study investigated
the effect of HBO-treatment in vivo on lens cytoskeletal proteins and MIP26 which
are also known to undergo alteration with age. Young (2-month-old) and old (18
month-old) guinea pigs were treated 15 and 30 times with HBO (3 times per week
with 2.5 atmospheres of 100% oxygen for 2.5 hr periods). SDS-PAGE and Western
blotting showed that HBO-treatment of the older animals accelerated the age
related loss of five nuclear cytoskeletal proteins including actin, vimentin,
ankyrin, alpha-actinin and tubulin, compared to levels present in age-matched
controls (effects on spectrin and the beaded filaments were not investigated in
this study). Treatment of the young animals with HBO produced losses which were
primarily associated with concentrations of the nuclear alpha- and beta-tubulins;
these cytoskeletal proteins were observed to be most sensitive to the induced
oxidative stress, and were affected earliest in the study. Disulfide
crosslinking, rather than proteolysis, appeared to be the main cause of the HBO
induced cytoskeletal protein loss (elevated levels of calcium, which might have
induced proteolysis, were not found in the experimental nuclei). Loss of MIP26
was observed only in the older guinea pigs treated 30 times with HBO; both
disulfide-crosslinking and degradation to MIP22 were associated with the
disappearance. Thus, nuclear MIP26 was susceptible to oxidative stress, but less
so than the cytoskeletal proteins, particularly the tubulins. No cortical effects
on either MIP26 or the cytoskeletal proteins were observed under any of the
treatment protocols. No direct link was observed between an HBO-induced increase
in NLS (observed in both the young and old animals using slit-lamp biomicroscopy)
and losses of either MIP26 or the cytoskeletal proteins. The appearance of HBO
induced nuclear opacity without any change in the levels of nuclear sodium,
potassium or calcium is similar to that observed previously for human senile pure
nuclear cataracts. The results provide additional evidence that molecular oxygen
can enter the nucleus of the lens and promote age-related events. The observed
effects on MIP26 and the cytoskeletal proteins are indicative of an increased
level of lens nuclear oxidative stress in the HBO model, possibly a precursor to
nuclear cataract.
PMID- 10192810
TI - Announcements
PMID- 10192811
TI - Introduction.
PMID- 10192809
TI - Functional difference of TGF-beta isoforms regulating corneal wound healing after
excimer laser keratectomy.
PMID- 10192821
TI - Clozapine preferentially increases dopamine release in the rhesus monkey
prefrontal cortex compared with the caudate nucleus.
AB - Despite substantial differences between species in the organization and
elaboration of the cortical dopamine innervation, little is known about the
pharmacological response of cortical or striatal sites to antipsychotic
medications in nonhuman primates. To examine this issue, rhesus monkeys were
chronically implanted with guide cannulae directed at the principal sulcus,
medial prefrontal cortex, premotor cortex, and caudate nucleus. Alterations in
dopamine release in these discrete brain regions were measured in response to
administration of clozapine or haloperidol. Clozapine produced significant and
long-lasting increases in dopamine release in the principal sulcus, and to a
lesser extent, in the caudate nucleus. Haloperidol did not produce a consistent
effect on dopamine release in the principal sulcus, although it increased
dopamine release in the caudate. Clozapine's preferential augmentation of
dopamine release in the dorsolateral prefrontal cortex supports the idea that
clozapine exerts its therapeutic effects in part by increasing cortical dopamine
neurotransmission.
PMID- 10192822
TI - d,l-fenfluramine response in impulsive personality disorder assessed with
[18F]fluorodeoxyglucose positron emission tomography.
AB - Reduced serotonergic activity has been associated with impulsive aggression in
personality disordered patients in metabolite and pharmacologic challenge
studies. This study used positron emission tomography to explore whether reduced
serotonergic function occurs in critical brain regions such as orbital frontal
and cingulate cortex that, may play a role in modulating aggression. Six
impulsive-aggressive patients and five healthy volunteers were evaluated for
changes in regional glucose metabolism after administration of the serotonergic
releasing agent d,l-fenfluramine (60 mg, p.o.) or placebo. Volunteers
demonstrated increases in orbital frontal and adjacent ventral medial frontal
cortex, cingulate, and inferior parietal cortex, whereas impulsive-aggressive
patients showed no significant increases in glucose metabolism after fenfluramine
in any region. Compared with volunteers, patients showed significantly blunted
metabolic responses in orbital frontal, adjacent ventral medial and cingulate
cortex, but not in inferior parietal lobe. These results are consistent with
reduced serotonergic modulation of orbital frontal, ventral medial frontal, and
cingulate cortex in patients with impulsive-aggressive personality disorders.
PMID- 10192823
TI - 5-HT modulation of dopamine release in basal ganglia in psilocybin-induced
psychosis in man--a PET study with [11C]raclopride.
AB - The modulating effects of serotonin on dopamine neurotransmission are not well
understood, particularly in acute psychotic states. Positron emission tomography
was used to examine the effect of psilocybin on the in vivo binding of
[11C]raclopride to D2-dopamine receptors in the striatum in healthy volunteers
after placebo and a psychotomimetic dose of psilocybin (n = 7). Psilocybin is a
potent indoleamine hallucinogen and a mixed 5-HT2A and 5-HT1A receptor agonist.
Psilocybin administration (0.25 mg/kg p.o.) produced changes in mood,
disturbances in thinking, illusions, elementary and complex visual hallucinations
and impaired ego-functioning. Psilocybin significantly decreased [11C]raclopride
receptor binding potential (BP) bilaterally in the caudate nucleus (19%) and
putamen (20%) consistent with an increase in endogenous dopamine. Changes in
[11C]raclopride BP in the ventral striatum correlated with depersonalization
associated with euphoria. Together with previous reports of 5-HT receptor
involvement in striatal dopamine release, it is concluded that stimulation of
both 5-HT2A and 5-HT1A receptors may be important for the modulation of striatal
dopamine release in acute psychoses. The present results indirectly support the
hypothesis of a serotonin-dopamine dysbalance in schizophrenia and suggest that
psilocybin is a valuable tool in the analysis of serotonin-dopamine interactions
in acute psychotic states.
PMID- 10192824
TI - Pituitary-adrenal cortical responses to low-dose physostigmine and arginine
vasopressin administration in normal women and men.
AB - Animal studies indicate that central cholinergic neurotransmission stimulates CRH
secretion, but several human studies suggest that the hypothalamo-pituitary
adrenal cortical (HPA) axis may be activated only by doses of cholinergic
agonists that produce noxious side effects and, by inference, a nonspecific
stress response. Physostigmine (PHYSO), a reversible cholinesterase inhibitor,
was administered to normal women and men at a dose that elevated plasma ACTH1-39,
cortisol, and arginine vasopressin (AVP) concentrations but produced few or no
side effects. Exogenous AVP also was administered alone and following PHYSO, to
determine if it would augment the effect of PHYSO on the HPA axis. Fourteen
normal women and 14 normal men matched to the women on age and race underwent
four test sessions 5 to 7 days apart: PHYSO (8 micrograms/kg i.v.), AVP (0.08
U/kg i.m.), PHYSO plus AVP, and saline control. Serial blood samples taken before
and after pharmacologic challenge were analyzed for ACTH1-39, cortisol, and AVP.
PHYSO and AVP administration produced no side effects in about half the subjects
and mild side effects in the other half, with no significant female-male
differences overall. There also were no significant female-male differences in
ACTH1-39 or cortisol responses to AVP. In contrast, the men had significantly
greater ACTH1-39 responses to PHYSO administration than did the women. The
endogenous AVP response to PHYSO also was significantly greater in the men than
in the women, and the ACTH1-39 and AVP responses to PHYSO were significantly
correlated in the men (both = +0.70) but not in the women. None of the hormone
responses was significantly correlated with the presence or absence of side
effects in either group of subjects. These results indicate a greater sensitivity
of the HPA axis to low-dose PHYSO in normal men than in normal women, which
likely is mediated by increased secretion of AVP. The lack of difference in side
effects between the two groups of subjects and the lack of significant
correlations between presence or absence of side effects and hormone responses in
either group suggest that the increased hormone responses in the men were due to
increased responsivity of central cholinergic systems and not to a nonspecific
stress response.
PMID- 10192825
TI - Effects of fluoxetine on the polysomnogram in outpatients with major depression.
AB - This study investigated the effects of open-label fluoxetine (20 mg/d) on the
polysomnogram (PSG) in depressed outpatients (n = 58) who were treated for 5
weeks, after which dose escalation was available (< or = 40 mg/d), based on
clinical judgment. Thirty-six patients completed all 10 weeks of acute phase
treatment and responded (HRS-D < or = 10). PSG assessments were conducted and
subjective sleep evaluations were gathered at baseline and at weeks 1, 5, and 10.
Of the 36 subjects who completed the acute phase, 17 were reevaluated after 30
weeks on continuation phase treatment and 13 after approximately 7 weeks (range 6
8 weeks) following medication discontinuation. Acute phase treatment in
responders was associated with significant increases in REM latency, Stage 1
sleep, and REM density, as well as significant decreases in sleep efficiency,
total REM sleep, and Stage 2 sleep. Conversely, subjective measures of sleep
indicated a steady improvement during acute phase treatment. After fluoxetine was
discontinued, total REM sleep and sleep efficiency were found to be increased as
compared to baseline.
PMID- 10192826
TI - Guanfacine, but not clonidine, improves planning and working memory performance
in humans.
AB - The present study compares, using a double-blind, placebo controlled design the
effects of two alpha 2-agonists, clonidine (0.5, 2, and 5 micrograms/kg) and
guanfacine (7 and 29 micrograms/kg) on spatial working memory, planning and
attentional set-shifting, functions thought to be dependent on the "central
executive" of the prefrontal cortex. Blood pressure and the subjective feeling of
sedation were affected equally by clonidine and guanfacine. The 0.5 microgram/kg
and 5 micrograms/kg doses of clonidine disrupted spatial working memory, but the
medium dose had no effect. The 0.5 and 2 micrograms/kg doses of clonidine
increased impulsive responding in the planning test. The 5 micrograms/kg dose of
clonidine slowed responding at effortful levels of planning and attentional set
shifting tests. The 29 micrograms/kg dose of guanfacine improved spatial working
memory and planning. Guanfacine had no effect on attentional set-shifting. These
data indicate that guanfacine improved planning and spatial working memory, but
clonidine dose-dependently disrupted performance. It is possible that the greater
selectivity of guanfacine for alpha 2A-adrenoceptor subtype may underlie its
differences from clonidine.
PMID- 10192827
TI - Reinstatement of alcohol-seeking behavior by drug-associated discriminative
stimuli after prolonged extinction in the rat.
AB - Clinical observations suggest that stimuli associated with the availability or
consumption of ethanol can evoke subjective feelings of craving and trigger
episodes of relapse in abstinent alcoholics. To study the motivational
significance of alcohol-related environmental cues experimentally, the effects of
discriminative stimuli previously predictive of alcohol availability on the
reinstatement of ethanol-seeking behavior were examined. Wistar rats were trained
to lever-press for 10% (w/v) ethanol or water in the presence of distinct
auditory cues. The rats were then subjected to an extinction phase where lever
presses had no scheduled consequences. After extinction, the animals were exposed
to the respective auditory cues without the availability of ethanol or water.
Neither the ethanol (SA+) nor water-associated (SA-) auditory cue increased
responding over extinction levels. In contrast, subsequent presentation of an
olfactory cue associated with ethanol (SO+), but not a water-associated (SO-) cue
significantly reinstated lever pressing behavior in the absence of the primary
reinforcer. Moreover, responding elicited by the concurrent presentation of the
SO+ and SA+ was selectively attenuated by the opiate antagonist naltrexone (0.25
mg/kg; s.c.). The results suggest that ethanol-associated cues can reinstate
extinguished ethanol-seeking behavior in rats, but that the efficacy of these
stimuli may be modality-specific. In addition, the present procedures may be
useful for studying neurobiological mechanisms of alcohol-seeking behavior and
relapse.
PMID- 10192828
TI - O- and N-demethylation of venlafaxine in vitro by human liver microsomes and by
microsomes from cDNA-transfected cells: effect of metabolic inhibitors and SSRI
antidepressants.
AB - The biotransformation of venlafaxine (VF) into its two major metabolites, O
desmethylvenlafaxine (ODV) and N-desmethylvenlafaxine (NDV) was studied in vitro
with human liver microsomes and with microsomes containing individual human
cytochromes from cDNA-transfected human lymphoblastoid cells. VF was coincubated
with selective cytochrome P450 (CYP) inhibitors and several selective serotonin
reuptake inhibitors (SSRIs) to assess their inhibitory effect on VF metabolism.
Formation rates for ODV incubated with human microsomes were consistent with
Michaelis-Menten kinetics for a single-enzyme mediated reaction with substrate
inhibition. Mean parameters determined by non-linear regression were: Vmax = 0.36
nmol/min/mg protein, K(m) = 41 microM, and Ks 22901 microM (Ks represents a
constant which reflects the degree of substrate inhibition). Quinidine (QUI) was
a potent inhibitor of ODV formation with a Ki of 0.04 microM, and paroxetine (PX)
was the most potent SSRI at inhibiting ODV formation with a mean Ki value of 0.17
microM. Studies using expressed cytochromes showed that ODV was formed by CYP2C9,
-2C19, and -2D6. CYP2D6 was dominant with the lowest K(m), 23.2 microM, and
highest intrinsic clearance (Vmax/K(m) ratio). No unique model was applicable to
the formation of NDV for all four livers tested. Parameters determined by
applying a single-enzyme model were Vmax = 2.14 nmol/min/mg protein, and K(m) =
2504 microM. Ketoconazole was a potent inhibitor of NDV production, although its
inhibitory activity was not as great as observed with pure 3A substrates. NDV
formation was also reduced by 42% by a polyclonal rabbit antibody against rat
liver CYP3A1. Studies using expressed cytochromes showed that NDV was formed by
CYP2C9, -2C19, and -3A4. The highest intrinsic clearance was attributable to
CYP2C19 and the lowest to CYP3A4. However the high in vivo abundance of 3A
isoforms will magnify the importance of this cytochrome. Fluvoxamine (FX), at a
concentration of 20 microM, decreased NDV production by 46% consistent with the
capacity of FX to inhibit CYP3A, 2C9, and 2C19. These results are consistent with
previous studies that show CYP2D6 and -3A4 play important roles in the formation
of ODV and NDV, respectively. In addition we have shown that several other CYPs
have important roles in the biotransformation of VF.
PMID- 10192829
TI - Ziprasidone 80 mg/day and 160 mg/day in the acute exacerbation of schizophrenia
and schizoaffective disorder: a 6-week placebo-controlled trial. Ziprasidone
Study Group.
AB - In this double-blind study, patients with an acute exacerbation of schizophrenia
or schizoaffective disorder were randomized to receive either ziprasidone 80
mg/day (n = 106) or 160 mg/day (n = 104) or placebo (n = 92), for 6 weeks. Both
doses of ziprasidone were statistically significantly more effective than placebo
in improving the PANSS total, BPRS total, BPRS core items, CGI-S, and PANSS
negative subscale scores (p < .05). Ziprasidone 160 mg/day significantly improved
depressive symptoms in patients with clinically significant depression at
baseline (MADRS > or = 14, over-all mean 23.5) (p < .05) as compared with
placebo. The percentage of patients experiencing adverse events was similar in
each treatment group, and resultant discontinuation was rare. The most frequent
adverse events associated with ziprasidone were generally mild dyspepsia, nausea,
dizziness, and transient somnolence. Ziprasidone was shown to have a very low
liability for inducing movement disorders and weight gain. The results indicate
that ziprasidone is effective and well tolerated in the treatment of the
positive, negative, and depressive symptoms of an acute exacerbation of
schizophrenia or schizoaffective disorder.
PMID- 10192830
TI - Serotonin transporter genotype and seasonal variation in serotonin function.
PMID- 10192832
TI - The future of neurophysiology in neuropsychopharmacology.
PMID- 10192833
TI - The African monogenean gyrodactylid genus Macrogyrodactylus Malmberg, 1957, and
the reporting of three species of the genus of Clarias gariepinus in South
Africa.
AB - Three different species of the genus Macrogyrodactylus Malmberg, 1957, collected
from the gills and skin of Clarias gariepinus (Burchell, 1822) from the Middle
Letaba Dam and Mokgoma-Matlala Dam in South Africa were examined and identified.
This is the first record of a species of the genus in South Africa. The three
species are M. congolensis (Prudhoe, 1957)--found on the skin, M. clarii Gussev,
1961 and M. karibae Douellou & Chishawa, 1995--found on the gills. The last
species is elevated to the status of a species having been described previously
as a subspecies of M. congolensis. The present study presents and discusses the
value of some of the taxonomic characters which can be used to differentiate the
species of the genus. The shape and size of the sclerites of the haptor are found
to be the most reliable characters. Only four species of the genus, namely M.
polypteri and the three above-named species are regarded to be valid. Three
species, namely M. latesi Paperna, 1969, M. anabantii Paperna, 1973 and M.
ctenopomii Paperna, 1973 are regarded as species inquirenda. Generic diagnoses,
measurements and illustrations of the sclerites of the four valid species are
presented and a key for their differentiation is provided. The development of the
gyrodactylid population on C. gariepinus during the filling of the Middle Letaba
Dam in South Africa is discussed.
PMID- 10192834
TI - Experimental studies on the life-cycle of Sebekia wedli (Pentastomida:
Sebekidae).
AB - Four young Nile crocodiles (Crocodylus niloticus) were infected with infective
pentastome larvae obtained from naturally infected Mozambique bream, Oreochromis
mossambicus, and red-breasted bream, Tilapia rendalli swierstrai in the Kruger
National Park. At day 95 post infection one of the crocodiles died and three
female and four male S. wedli were recovered from its lungs. One pair was found
in copula but the uteri of the females were not yet developed. Males and females
were of about equal size. After 226 d post infection the three remaining
crocodiles were sacrificed. Two of these harboured no pentastomes but eight were
taken from the lungs of the third. The sex ratio had shifted in favour of the
females, seven females and one male being present. One of the females recovered
from the crocodiles was placed in saline and produced 3,400 eggs. These were used
to infect eight guppies, Poecilia reticulata. Within 31 d two infective stages of
S. wedli had developed in one of the guppies thus completing the life-cycle of
the pentastome. S. wedli recovered from experimentally infected final hosts were
slightly smaller than those recovered from a wild-caught final host.
PMID- 10192835
TI - Antigenic and genetic analysis of canine parvoviruses in southern Africa.
AB - Canine parvovirus (CPV) is a significant pathogen of domestic and free-ranging
carnivores all over the world. It suddenly appeared at the end of the 1970s and
most likely emerged as a variant of the well known feline panleukopenia virus
(FPV). During its adaptation to the new host, the domestic-dog, the virus has
changed its antigenic profile twice giving rise to two new antigenic types, CPV
2a and CPV-2b. These new types have replaced the original type CPV-2 in the
United States of America, Europe and Japan. However, no data about the prevalence
of the new antigenic types on the African continent are available. In this study,
128 recent parvovirus isolates from South Africa and Namibia were antigenically
typed with type-specific monoclonal antibodies. No original CPV-2 viruses were
found and its complete replacement by the new antigenic types conforms to the
situation in other parts of the world. The predominant strain found in southern
Africa was CPV-2b (66%), which differs from the situation in Europe and Japan
where CPV-2a is the most prevalent type. Analysis of the capsid protein DNA
sequences of four selected African isolates gave no hint of a specific African
parvovirus lineage.
PMID- 10192836
TI - A study on bluetongue virus infection in Saudi Arabia using sentinel ruminants.
AB - Four sentinel herds comprising cattle, sheep and goats were established at
various localities in Saudi Arabia. Maternal bluetongue antibodies were detected
in all four sentinel herds but disappeared in 4-6 months, immediately followed by
seroconversion in all. Serological results indicated that the animals were
recently exposed to BT virus serotypes 10, 12, 15 and 20. The epidemiology of the
disease in Saudi Arabia is discussed.
PMID- 10192837
TI - Light and electron microscopical observations on the terminal airways and alveoli
of the lung of the SA (Cape) fur seal Arctocephalus pusillus.
AB - During activities of the Sea Fisheries Research Institute at Kleinzee, lung
samples from six South African fur seals were collected. The terminal airways
showed pseudostratified ciliated columnar epithelium with numerous goblet cells
and occasional brush cells. Smooth muscle, cartilage and submucosal glands were
also present. The epithelium changed over a short distance, in the smaller
airways, through pseudostratified columnar non-ciliated to simple cuboidal
epithelium with no goblet cells. The columnar non-ciliated cells contained
secretory granules, which appeared to be serous. No Clara cells were found.
Cartilage and muscle were present throughout, up to the origin of the alveolar
ducts, but the glands disappeared together with the goblet cells. Alveoli were
lined by types one and two alveolar epithelial cells, with subepithelial
capillaries. They were divided by an alveolar septum with a well developed
alveolar knob. This knob contained elastic fibres and fibroblasts, but not the
smooth muscle cells which are present in terrestrial mammals and in Phocidae.
PMID- 10192838
TI - Models for heartwater epidemiology: practical implications and suggestions for
future research.
AB - We present a simple model of the dynamics of heartwater that we use to explore
and better understand various aspects of this disease. We adapted the Ross
Macdonald model for malaria epidemiology so that we could consider both host and
vector populations, and evaluate the interactions between the two. We then use
two more biologically detailed models to examine heartwater epidemiology. The
first includes a carrier state and host mortality, and the second includes
density dependence. The results from all three models indicate that a stable
equilibrium with high disease levels is probably the standard situation for
heartwater (R0 between 5.7 and 22.4). More than 80% of cattle become infected
with heartwater if only 12% of infected tick bites produce an infection in
cattle, if tick burdens are as low as only five ticks per host per day, or if
tick lifespans are as short as 7 d. A host recovery rate of 30 d results in over
50% of the cattle becoming infected with heartwater. Our analyses indicate that
it is quite difficult to prevent the establishment and maintenance of high levels
of heartwater in a herd, thereby supporting previous suggestions that any
attempts at controlling this disease through stringent tick control regimens are
not warranted.
PMID- 10192839
TI - The efficacy of used engine oil against ticks on cattle.
AB - The study was conducted in a peri-urban agricultural system at Botshabelo, a city
in the south-eastern Free State. A questionnaire survey revealed that 88.5% of
cattle farmers in the area experienced problems related to ticks and tick-borne
diseases. Because of the cost of commercial acaricides the Botshabelo farmers use
alternative, cheaper methods of tick control, including the application of used
engine oil. The specific aim of the study was to determine whether used engine
oil can effectively control ticks on cattle. From March to August 1996 the tick
burdens of ten control animals and six animals treated by their owner with used
engine oil were compared. The total tick burdens for the 6 month period differed
significantly between the two experimental groups. The efficacy of the used
engine oil on the treated group varied between 15.1% and 64.8% with a mean of
38.1%. Although commercial acaricides can be more cost-effective, the application
of used engine oil can be useful to reduce tick numbers on cattle during periods
of peak abundance. Another advantage in that the use of the oil will not
influence existing endemic stability of Anaplasma marginale and Babesia bigemina
infections because of the residual tick burdens after treatment.
PMID- 10192840
TI - Coccidia oocysts in the faeces of farmed ostrich (Struthio camelus) chicks in
Botswana.
AB - Coccidia oocysts were demonstrated in the faeces of 53 (about 34%) of 156
apparently healthy ostrich chicks. Young chicks had the highest proportion of
infestation while those more than 9 weeks old had no oocysts at all in their
faeces. These coccidia may be considered no pathogenic since the infected chicks
grew normally without any evidence of diarrhoea.
PMID- 10192841
TI - Epidemiology of tick-borne diseases of cattle in Botshabelo and Thaba Nchu in the
Free State Province.
AB - A seroepidemiological study was conducted on 151 cattle from the Botshabelo and
Thaba Nchu areas in the central Free State Province of South Africa, two areas
where small scale, peri-urban cattle farming is practised. An indirect
fluorescent antibody test was used to test for Babesia bigemina and B. bovis
antibodies. To test for Anaplasma marginale antibodies a competitive inhibition
enzyme-linked immunosorbent assay method was used. There were no significant
differences in serological test results between the cattle from Botshabelo and
those from Thaba Nchu. The herd (two areas combined) had an average
seroprevalence of 62.42% to B. bigemina, 19.47% to B. bovis and 98.60% to A.
marginale. Based on the percentage of cattle that were seropositive to B.
bigemina the immune status of cattle in the Botshabelo-Thaba Nchu area is
approaching a situation of endemic stability. With reference to A. marginale, the
high seroprevalence is indicative of a situation of endemic stability. The
occurrence of B. bovis antibodies in the cattle is difficult to explain as
Boophilus microplus ticks do not occur in the area in which the study was
conducted.
PMID- 10192842
TI - Individual host variations in tick infestations of cattle in a resource-poor
community.
AB - Relative resistance levels of cattle against tick infestations in the communal
grazing area of Botshabelo in the south-eastern Free State were determined. The
objective was to establish whether differences in resistance can be exploited to
contribute to tick control methods used by small-scale farmers in resource-poor
environments. Ten cows (Bos taurus crosses) between the ages of 18 months and
four years were used and tick counts were conducted once a month over a period of
12 months to compare their total tick burdens. Tick burdens of the various
animals were compared mutually as well as with the mean tick burden of the group
as a whole. Tick numbers varied throughout the year on all individuals but some
animals consistently tended to have either higher or lower numbers than the mean
of the group. Tick burdens on cattle classified as having a relatively low
resistance to tick infestations increased eleven-fold from January to June 1996
compared to a six-fold increase on cattle categorized as belonging to the high
resistance group. Twenty-eight percent of the cattle in the total study group
carried 50% of the ticks collected (60,079). It is recommended that farmers in
the region visually assess B. decoloratus burdens, the most abundant tick
species, and sell or cull the most susceptible animals first in their normal
program of utilization of the animals. This should eventually result in the
direct improvement of the overall tick resistance of their cattle herds.
PMID- 10192843
TI - A nucleotide-specific polymerase chain reaction assay to differentiate rabies
virus biotypes in South Africa.
AB - Antigenic and nucleotide sequence analyses have shown that two distinct biotypes
of rabies virus are circulating in South Africa. One of these typically infects
members of the family Canidae, while the other comprises a heterogeneous group of
apparently indigenous viruses, infecting members of the Viverridae family. In
recent times, it has become evident that a considerable amount of cross-infection
may occur and the manifestation of viverrid rabies in non-viverrid animals in
particular appears to have become more commonplace. Consequently, the need to
rapidly distinguish between rabies virus biotypes has become increasingly
important in efforts to monitor the epidemiology of rabies in the southern
African region. In this study, a nested polymerase chain reaction (PCR) assay was
developed to distinguish between these two groups of rabies viruses. Consensus
oligonucleotides were used to amplify the cytoplasmic domain of the rabies virus
glycoprotein and the adjacent intergenic region. The resultant amplicon was
subsequently used as template in second round heminested PCR in the presence of
type-specific primers, thereby successfully generating amplicons of
characteristic size for each biotype.
PMID- 10192844
TI - Tick diversity, abundance and seasonal dynamics in a resource-poor urban
environment in the Free State Province.
AB - The objectives of this study were to determine the diversity, seasonal dynamics
and abundance of ticks infesting cattle in urban, small-scale farming communities
in and around Botshabelo and Thaba Nchu in the eastern Free State Province, South
Africa. A total of ten cattle, ear-tagged for individual identification, were
investigated monthly at each of five localities. Adult ticks were removed from
the right hand side of each animal and placed in containers filled with 70%
ethanol. They were subsequently identified and their numbers quantified. Immature
Otobius megnini were counted but not removed. A total of 244,538 adult ticks of
ten different species were collected over the 12-month study period. The tick
species, in decreasing order of relative abundance, were: Boophilus decoloratus
(87.26%), Rhipicephalus evertsi evertsi (6.86%), Hyalomma marginatum rufipes
(2.42%), Otobius megnini (1.85%) Rhipicephalus follis (0.76%), Rhipicephalus
gertrudae (0.54%), Rhipicephalus sp. (0.21%), Ixodes rubicundus (0.08%), Hyalomma
truncatum (0.01%) and Margaropus winthemi (0.004%). The three most abundant
species, namely B. decoloratus, R. evertsi evertsi and H. marginatum rufipes,
occurred at all localities but with significant differences in abundance. M.
winthemi ticks occurred only in the Thaba Nchu area and were not found at any of
the there localities in Botshabelo. Significant differences in tick burdens
between the six warm months (September to February) and the six cooler months
(March to August) were found for most of the species recorded. Boophilus
decoloratus occurred in significantly higher numbers in autumn (March to May) and
winter (June to August) compared to spring (September to November) and summer
(December to February), with 76.8% of the total B. decoloratus burden occurring
during the cooler months.
PMID- 10192845
TI - Correlation between ability of Ornithobacterium rhinotracheale to agglutinate red
blood cells and susceptibility to fosfomycin.
AB - Twenty five freeze-dried isolates of Ornithobacterium rhinotracheale were used
for the determination of minimum inhibitory concentrations (MIC) against the
antibiotic fosfomycin (Fosbac, produced by Bedson SA, consisting of a 25% mixture
of fosfomycin). The same isolates were tested for their ability to
haemagglutinate chicken red blood cells. Ten of the 25 isolates were found to be
susceptible to fosfomycin (MIC values below 128 ug/ml). All of these isolates
were able to agglutinate red blood cells. This is the first report on the ability
of O. rhinotracheale to agglutinate red blood cells. The remaining 15 isolates
were resistant to fosfomycin (MIC values above 128 ug/ml). Only five of these
isolates were found to have the ability to agglutinate red blood cells. There
appears to be a correlation between the ability of O. rhinotracheale isolates to
agglutinate red blood cells and their susceptibility to fosfomycin. The ability
of certain isolates of O. rhinotracheale to agglutinate red blood cells, raises
the questions of differences in virulence between the isolates which can
agglutinate red blood cells and those which cannot and the use of this ability to
agglutinate red blood cells as an alternative method for serotyping O.
rhinotracheale.
PMID- 10192847
TI - [A 12-year retrospective on the cement-free prosthesis. SL (Self-Locking) femur
revision-prosthesis by Wagner].
PMID- 10192846
TI - Protein aggregation complicates the development of baculovirus-expressed African
horsesickness virus serotype 5 VP2 subunit vaccines.
AB - This paper describes the expression of a cloned African horsesickness virus
(AHSV) serotype 5 VP2-gene by a baculovirus recombinant that was generated by the
BAC-TO-BAC system. Immunization of horses with crude cell lysates containing
recombinant baculovirus-expressed AHSV5 VP2 did induce neutralizing antibodies,
but afforded only partial protection against virulent virus challenge. Further
analysis of partially protective crude cell lysates revealed that baculovirus
expressed AHSV5 VP2 was predominantly present in the form of insoluble
aggregates. Only approximately 10% of VP2 was present in a soluble form.
Immunization of guinea-pigs with aggregated and soluble forms of AHSV5 VP2
established that only soluble VP2 was capable of inducing neutralizing
antibodies. This finding adds a new dimension to the development of AHSV VP2s as
subunit vaccines. Further investigation is needed to limit formation of insoluble
aggregates and optimize conditions for producing VP2 in a form capable of
inducing protective immunity.
PMID- 10192848
TI - Implantable cardiac devices and Y2K (Y2K-year 2000)
PMID- 10192849
TI - Long-term survival after permanent pacemaker implantation in young adults: 30
year experience.
AB - The goal of the present study was to determine the etiology of conduction disease
and long-term outcome for young adults who undergo permanent pacemaker
implantation. Permanent pacing was performed in 232 patients aged 21-50 years,
135 males and 97 females, from 1965 through 1995. One hundred and twenty-six
subjects (54%) had evidence of structural heart disease, while idiopathic
conduction disease accounted for 46%. About half (54%) of 106 patients with
structural heart disease had surgically induced heart block. Pacing mode at
primary implantation was single chamber in 65% and dual chamber in 35%. Follow-up
ranged from 12-387 months, with a mean of 104-months. At the last follow-up, 133
of 232 patients (57%) were alive, 40 (17%) had died, 30 (13%) were lost to follow
up, 26 (11%) were transferred elsewhere, and 3 (1%) explanted. Patients with sick
sinus syndrome had similar outcomes to those with AV block. There was a sharp
decline in survival during the first six months; 7.5% of the sample died within
the first year following their first pacemaker operation. After the first year,
the decline in survival slowed and 70% of the patients could be expected to
survive beyond 20 years. The overall survival of young patients without
structural heart disease who received a permanent pacemaker was comparable to an
age- and sex-matched control population, while patients with structural heart
disease performed significantly worse than the control population.
PMID- 10192850
TI - Catheter tip orientation affects radiofrequency ablation lesion size in the
canine left ventricle.
AB - While some factors influencing size of RF lesions in ventricular tissue have been
characterized, the effects of catheter electrode-endocardial surface orientation
on lesion generation have not been investigated. Therefore, the effects of
parallel versus perpendicular catheter electrode-endocardial surface orientation
on dimensions of RF lesion produced with 4-, 6-, 8-, 10-, and 12-mm distal
electrode lengths were studied in 20 closed-chested dogs. Orientation was
established by biplane fluoroscopy and confirmed by intracardiac echocardiography
for the majority of energy deliveries (71%). RF voltage was titrated to maintain
constant catheter electrode temperature of 75 degrees C for 60 seconds. In the
perpendicular orientation, lesion size did not change significantly with
increasing electrode lengths. There was a statistically significant interaction
between electrode orientation and maximum lesion length (analysis of variance
[ANOVA] P = 0.04], lesion width (ANOVA P = 0.01), lesion area (ANOVA P = 0.02),
and estimated lesion volume (ANOVA P < 0.005) over all electrode lengths. With
parallel tip-tissue orientation, lesion size was a function of increasing
electrode length. For 4-, 6-, 8-, 10-, and 12-mm electrodes, maximum lesion
surface areas were 95 +/- 38, 97 +/- 38, 119 +/- 29, 147 +/- 52, and 147 +/- 67
mm2, respectively. For electrode lengths 8, 10, and 12 mm, estimated lesion
volumes were significantly greater with parallel orientation (P < 0.05 for all).
Thus, ventricular lesion size is dependent on catheter electrode length, but only
when the catheter is oriented parallel to the endocardial surface. This
information may be helpful in increasing lesion dimensions for RF ablation of
ventricular tachycardias.
PMID- 10192851
TI - Reduction of atrial fibrillation inducibility by radiofrequency ablation: an
experimental study.
AB - A study is made of the antifibrillatory effects of radiofrequency (RF)-induced
atrial lesions using nine Langendorff-perfused rabbit hearts in which the atrial
electrophysiological properties and atrial fibrillation (AF) inducibility were
modified by atrial stretching. Using a multiple electrode consisting of 121
unipolar electrodes, determinations were made of the atrial refractory periods,
conduction velocity, wavelength of the atrial activation process, and the
inducibility of sustained AF episodes (duration over 30 s) by atrial burst pacing
in four situations: (a) control; (b) following dilatation of the right atrium;
(c) after adding an RF linear lesion at the cava-tricuspid annulus isthmus; and
(d) after adding two RF linear lesions rounding the base of the right atrial
appendage and extending from the inferior zone of the sulcus terminalis to the
anterior wall of the appendage. Under control conditions, AF was not induced in
any of the experiments. The wavelengths were 10.5 +/- 1.2 cm for basic cycles of
250 ms and 6.6 +/- 0.5 cm for cycles of 100 ms. Following dilatation, a
significant decrease was recorded in the atrial refractory periods, conduction
velocity, and wavelength, which reached values of 6.1 +/- 0.7 cm (250-ms cycle, P
< 0.01), and 3.9 +/- 0.3 cm (100-ms cycle, P < 0.01); AF was induced in five
cases (P < 0.05). After producing the lesion at the cava-tricuspid isthmus, the
electrophysiological modifications induced by atrial dilatation persisted
(wavelength = 6.2 +/- 0.6 cm (250-ms cycle) and 4.3 +/- 0.3 cm (100-ms cycle); P
< 0.01 vs the control) and AF was triggered in eight cases (P < 0.0001). In turn,
on adding the two lesions at the right atrial free wall and appendage, AF was
induced only in one experiment (P = NS vs control), and the dilatation-induced
decrease in refractoriness and wavelength was attenuated. Nevertheless,
differences remained significant with respect to the controls, with the exception
of the functional refractory periods determined at cycles of 100 ms. In this
phase, the wavelength was 6.6 +/- 0.7 cm (250-ms cycle, P < 0.01 vs control) and
4.9 +/- 0.5 cm (100-ms cycle; P < 0.05). Atrial conduction between the zones
separated by the lesions was blocked at any frequency, or selectively at rapid
atrial activation frequencies. IN CONCLUSION: (a) the production of three linear
lesions in the right atrium (cava-tricuspid isthmus, atrial appendage, and
inferior free wall) reduces AF inducibility in the experimental model used; (b)
conduction block (either absolute or frequency dependent) through the lesions,
reduction in tissue mass caused by lesion creation, and possibly the attenuation
of the shortening of atrial refractoriness and wavelength in the zones not
separated by the lesions are implicated in the reduction of AF inducibility; and
(c) the single lesion in the cava-tricuspid isthmus does not impede AF
inducibility.
PMID- 10192852
TI - Implantable defibrillators impedance measurement using pacing pulses versus shock
delivery with intact and modified high voltage lead system.
AB - At present the only method for measuring the high voltage system lead impedance
in patients with an ICD is to deliver a low energy test shock. This is painful,
requires sedation, and carries a risk of ventricular fibrillation induction. We
sought to assess the shock lead and electrode function by calculating IMP using
low voltage pacing pulses, and compared it to the measured impedance of a shock
through the same lead. This was performed in both an intact and a modified lead
system in order to mimic common clinical scenarios that alter lead system IMP
(e.g., lead fracture). In an anesthesized canine model (n = 12) a standard (S)
transvenous defibrillation lead (TDL), a modified (M) TDL (two-thirds of coil
covered with heat-shrunk tubing), an active can (AC), and a M epicardial patch
(EP) (two of four coils were disconnected) were used. Three configurations (C)
were tested: C1:S/TDL-->AC, C2:M/TDL-->AC, and C3:M/TDL-->MEP. A measured IMP was
obtained by an ICD using a 5-J shock as control. IMP was calculated using a 5-J
shock, pacing pulses of 10-, 5-, 2-, and 1-V amplitude, as well as from a square
wave drive train of low amplitude/high frequency signals (1 and 0.2 V, at 10 kHz)
in all Cs. Ohm's law (V = IR) was utilized for measuring calculated IMP. As the
surface area of the high voltage lead system decreased, the mean measured IMP
(control) increased from C 1 to 3 (63 +/- 10, 95 +/- 4, and 127 +/- 20 omega,
respectively). The correlation of calculated IMP from all Cs to measured
impedance (control) remained high throughout the IMP range (range of correlation
coefficient (r): 0.921-0.981). Calculated IMP using delivery of pacing pulses is
highly correlated to IMP measured during shock delivery. This correlation remains
high over a clinically significant range of high voltage lead system IMP changes.
This study suggests that pacing pulses can be used to predict the IMP changes in
the high voltage lead system which may occur clinically, reducing the need to
deliver a shock for IMP measurement.
PMID- 10192853
TI - Modulation of the atrioventricular node conduction to achieve rate control in
patients with atrial fibrillation: long-term results.
AB - Modulation of the AV node reduces the ventricular rate during AF, without
affecting AV conduction during sinus rhythm. Acute and long-term results of AV
node modulation in 75 patients with AF and severe related symptoms of heart
failure are presented in this study. The procedure involved, in all cases, the
selective ablation of the posterior inputs to the AV node; in a subgroup of 15
patients with poor modification of AV conduction properties, a sequential
approach involving subsequent anterior input ablation was performed. The
procedure caused acutely a prolongation of the Wenckebach cycle length (38
patients in sinus rhythm) from 334 +/- 88 to 470 +/- 80 ms (P < 0.01), and a
reduction of the average ventricular rate (37 patients in AF) from 154 +/- 31 to
88 +/- 40 beats/min (P < 0.01); permanent complete AV block was induced in 9 of
75 patients (12%). Considering the "sequential" approach, an increase of the
Wenckebach cycle length from 362 +/- 50 to 530 +/- 45 ms (P < 0.01) and a
reduction of the average heart rate in patients with AF from 158 +/- 16 to 81 +/-
20 beats/min (P < 0.01) was obtained in this subgroup of patients, in whom the AH
interval prolonged from 93 +/- 12 to 175 +/- 27 ms, and no complete AV block was
observed. At a mean follow-up of 23 +/- 9 months (range 2-48), the mean number of
hospital admissions per patient per year decreased from 4.2 to 0.2. Five of 49
patients with paroxysmal AF and 3 of 26 patients with chronic AF had high rate
recurrences (1 > 120 beats/min) that caused severe palpitations; these patients
were considered as late clinical failures (8/75; 11%). All patients reported a
substantial subjective improvement and an increased exercise tolerance, as
documented by a semiquantitative questionnaire. There were no episodes of late AV
block or sudden cardiac deaths. In conclusion, modulation of the AV node--either
by slow pathway ablation, or by a "sequential" posterior and anterior approach in
refractory patients--allows a long-term control of the ventricular rate and
prevents the recurrence of severe clinical symptoms in more than 75% of patients
with drug refractory AF.
PMID- 10192854
TI - The utility of quantitative body surface isoarea mapping for predicting
ventricular tachyarrhythmias.
AB - Noninvasive techniques, such as the signal averaged ECG, have been used to assess
risk of ventricular tachyarrhythmias (VT). However, these methods produce false
positive and negative results. The purpose of this study was to develop body
surface map algorithms which would enhance prediction of susceptibility to VT.
Fifty-three patients referred for programmed electrical stimulation were enrolled
in this study. All patients underwent signal averaged ECG, body surface map,
programmed electrical stimulation. Group I patients had no sustained inducible VT
and group II patients had either inducible sustained VT at electrophysiology
study or previously documented spontaneous, sustained VT. For body surface map
analysis, the difference between extrema on isoarea maps was calculated and
defined as the gradient range. An abnormal body surface map was defined as a QRST
gradient range < or = 109 mv.ms. The mean QRST gradient range in group II was
significantly < that in group I (P < 0.05). By logistic regression analysis, the
presence of coronary artery disease, a QRST gradient range < or = 109 mv.ms, an
EF < 40% and a signal averaged ECG QRS duration > 114 ms predicted VT. The
sensitivity, specificity, positive and negative predictive values for predicting
VT susceptibility of an algorithm which combines the signal averaged ECG QRS
duration and the QRST gradients were 0.93, 0.76, 0.79, and 0.91, respectively,
while those for the signal averaged ECG alone were 0.52, 0.69, 0.63, and 0.59 for
VT susceptibility. A combined body surface map-signal averaged ECG algorithm was
more sensitive in detecting susceptibility to VT than the signal averaged ECG
alone.
PMID- 10192855
TI - Quality of life in patients with complete heart block and paroxysmal atrial
tachyarrhythmias: a comparison of permanent DDIR versus DDDR pacing with mode
switch to DDIR.
AB - A prospective double-blind randomized crossover study was done in 15 patients
with complete heart block and intermittent ATs. The pacemaker was randomly
programmed to dual chamber inhibited rate responsive pacing (DDIR) and to DDDR
with mode switch, for 1 month each. An event recorder was given to the patients
and after each period, a QOL questionnaire was obtained. Based on telemetric
data, all but two patients had AT during follow-up. The duration and frequency of
these episodes were not related to mode settings. AV synchrony was better
preserved in DDDR (P < 0.05). Most symptom-related event recordings during DDIR
showed loss of AV synchrony; DDDR with mode switch caused symptoms due to
tracking of ST. Overall the QOL score was not different between the modes. Fewer
somatic complaints were noted during DDDR pacing than during baseline. DDIR
stimulation showed no difference. Twelve patients preferred the period of DDDR
pacing; one experienced severe symptoms during DDIR. In conclusion, patients with
paroxysmal AT, DDDR with mode switch, and DDIR had no influence on the
occurrence, nor on the duration of AT episodes. AV synchrony was better preserved
in DDDR, which was also associated with fewer somatic complaints compared to the
baseline. In DDDR, symptoms were observed when ST was tracked. QOL was
comparable, although more patients preferred DDDR.
PMID- 10192856
TI - Pectoral cardioverter defibrillators: comparison of prepectoral and submuscular
implantation techniques.
AB - The purpose of this study was to compare the two techniques of pectoral ICD
implantation, prepectoral and submuscular, performed by an electrophysiologist in
the catheterization laboratory with use of general or local anesthesia in 45
consecutive patients. Over a period of 30 months, we implanted pectoral
transvenous ICDs in 43 men and 2 women, aged 59 +/- 12 years, with use of general
(n = 20) or local (n = 25) anesthesia in the catheterization laboratory. Patients
had coronary (n = 30) or valvular (n = 4) disease, cardiomyopathy (n = 10) or no
organic disease (n = 1), a mean left ventricular ejection fraction of 31%, and
presented with ventricular tachycardia (n = 40) or fibrillation (n = 5). One-lead
ICD systems (18 Endotak, 10 Transvene/8 Sprint, 2 EnGuard) were used in 38
patients, 2-lead (5 Transvene, 1 EnGuard) systems in 6 patients, and 1
atrioventricular lead ICD system in 1 patient. The prepectoral technique was
employed in 29 patients with adequate subcutaneous tissue, while the submuscular
technique was used in 16 patients who had a thin layer of subcutaneous tissue.
The defibrillation threshold averaged 9-10 J in both groups and there were no
differences in pace/sense thresholds. All implants were entirely transvenous with
no subcutaneous patch. Biphasic ICD devices were employed in all patients. Active
or hot can devices were used in 39 patients. There were no complications,
operative deaths, or infections. Patients were discharged at a mean of 3 days.
All devices functioned well at predis-charge testing. Over 14 +/- 8 months, 20
patients received appropriate device therapy (antitachycardia pacing or shocks).
No late complications occurred. One patient died at 3 months of pump failure;
there were no sudden deaths. In conclusion, for exclusive pectoral implantation
of transvenous ICDs, electrophysiologists should master both prepectoral and
submuscular techniques. One can thus avoid potential skin erosion or need for
abdominal implantation in patients with a thin layer of subcutaneous tissue.
Finally, there are no differences in pacing or defibrillation thresholds between
the two techniques.
PMID- 10192857
TI - Effect of a class III antiarrhythmic drug on the configuration of dose response
curve for defibrillation.
AB - Antiarrhythmic agents with a Class III action are known to increase
defibrillation efficacy. We investigated whether a Class III drug simply shifts
the dose-response curve for defibrillation or more extensively alters the curve.
Forty-five dogs were divided into four groups according to the shock waveform and
the presence or absence of treatment with a novel Class III drug, MS-551 (2 mg/kg
bolus + 0.02 mg/kg per min). In addition to the conventional transcardiac DFT,
dose-response curves were obtained by fitting the results of 40 fibrillation
defibrillation sequences at five shock strengths to a logistic model. MS-551
significantly decreased DFT regardless of the shock waveform (control vs MS-551 =
306 +/- 79 V vs 229 +/- 72 V [monophasic shock, P < 0.05], or 227 +/- 42 V vs 176
+/- 26 V [biphasic shock, P < 0.005]). The dose-response curves in dogs treated
with MS-551 had a gentler slope than those without treatment, and the ratio of
the voltages corresponding to 50% and 90% defibrillation success (V90/V50) was
significantly greater in the MS-551 group (monophasic: 1.21 +/- 0.06 vs. 1.62 +/-
0.42 [P < 0.005], biphasic: 1.20 +/- 0.05 vs 1.37 +/- 0.18 [P < 0.01]). The
V90/DFT ratio was also significantly larger in the MS-551 group (monophasic: 1.22
+/- 0.12 vs 1.66 +/- 0.37 [P < 0.001]; biphasic: 1.19 +/- 0.11 vs 1.44 +/- 0.79
[P < 0.005]). Thus, this Class III drug decreased the shock strength
corresponding to relatively higher success rate (approximately 90%) less markedly
than that for moderate success rate (approximately 50%). These results suggest
that a Class III drug does not simply shift the dose response curve in proportion
to the change in DFT, but more extensively alters its configuration.
PMID- 10192858
TI - A gastroesophageal electrode for electrophysiological studies.
AB - A novel gastroesophageal electrode has been developed capable of atrial and
ventricular pacing. We performed electrophysiological studies using the
gastroesophageal electrode (Esothoracic) and compared the results with the
standard endocardial approach. The flexible polythene gastroesophageal electrode
was passed into the stomach under light sedation. Five ring electrodes, now
positioned in the lower esophagus were used for bipolar atrial pacing and
recording. Ventricular pacing was performed using a cathodic point source on the
gastroesophageal electrode tip; the indifferent electrode (anode) was a high
impedance chest pad. Parameters of sinus and AV nodal function were obtained by
atrial pacing. Programmed ventricular stimulation was performed using a standard
protocol. These electrophysiological parameters were subsequently determined
using the endocardial approach. There was close correlation between measurements
of sinus and AV node function using the two approaches in 48 subjects: sinus node
recovery time (SNRT) r2 = 0.70, corrected sinus node recovery time (CSNRT) r2 =
0.87, AV Wenckebach cycle length (AVWCL) r2 = 0.97. The degree of agreement
between the two approaches was estimated by the mean difference delta and
standard deviation of the difference sigma (SNRT delta = 40 ms, sigma = 257 ms;
CSNRT sigma = 14 ms, delta = 164 ms; AVWCL sigma = 7 ms, delta = 16 ms).
Programmed ventricular stimulation was performed in 15 of 48 subjects with known
or suspected ventricular tachyarrhythmias. Seven had ventricular tachycardia
induced using both esothoracic and endocardial programmed ventricular
stimulation. One subject was noninducible using esothoracic programmed
ventricular stimulation, but inducible at endocardial electrophysiological
studies. Another subject was inducible at esothoracic electrophysiological
studies, but noninducible using endocardial programmed ventricular stimulation.
Six subjects were noninducible using both endocardial and esothoracic programmed
ventricular stimulation. The gastroesophageal electrode permits reliable atrial
and ventricular pacing without transvenous catheterization or fluoroscopy.
Electrophysiological parameters determined using this electrode are similar to
those obtained using endocardial stimulation.
PMID- 10192859
TI - Characteristics and radiofrequency catheter ablation of septal accessory
atrioventricular pathways.
AB - Septal accessory AV pathways are located in the complex AV septal space that also
contains the specialized conduction system. They have unique
electrocardiographical and electrophysiological characteristics to be
differentiated from free-wall accessory pathways. Some of the septal pathways
have AV nodelike conduction properties and produce a similar activation sequence
in the retrograde conduction. Several methods have been developed to distinguish
them from AV nodal pathways. Radiofrequency catheter ablation using the titration
method and endocardial approach without entrance into the coronary sinus is
effective in eliminating most of the septal accessory pathways without impairment
of AV conduction. However, some posteroseptal accessory pathways may require
energy application inside the coronary sinus, thus information of the coronary
sinus anatomy is important for preventing complication.
PMID- 10192860
TI - Narrow complex tachycardia showing an uncommon electrophysiological phenomenon
during its induction.
PMID- 10192861
TI - The impact of the millennium problem on implantable pacemakers and
defibrillators.
AB - The unpredictable behavior of computer systems on January 1, 2000, known as the
millennium problem or millennium 'bug,' also affects medical establishments and,
due to the large use of computers in all kind of applications, cardiological
clinics in particular. This review discusses the effect of the millennium
computer problem on the implantation procedures and follow-up registries of
implantable pacemakers and defibrillators. The review concludes that the
transition in the next millennium will not influence the proper functioning of
implanted pacemakers and defibrillators. The function of pacemaker/defibrillator
programmers seems to be safe and no major difficulties are anticipated. Pacemaker
databases and the logistics linked to the implantation and follow-up of patients
and their pacemaker may and probably will be affected by the millennium
transition. Using the FDA database on biomedical equipment, the actual status of
all biomedical devices can be assessed.
PMID- 10192862
TI - Sustained inhibition of a DDD pacemaker at rates below the programmed lower rate
during automatic PVARP extension.
AB - A patient with a Pacesetter Paragon III DDD pacemaker exhibited sustained
pacemaker inhibition at rates below the programmed lower rate during sinus rhythm
with marked first degree AV block. In this device, a pacemaker defined
ventricular extrasystole initiates automatic extension of the postventricular
atrial refractory period to 480 ms and the atrial escape interval to 830 ms
regardless of the programmed lower rate. Sustained pacemaker inhibition at rates
below the programmed lower rate occurred because the P wave fell continually in
the extended postventricular atrial refractory period, and the conducted QRS
complex initiated a pacemaker ventricular extrasystole response with atrial
escape interval extension. This process continued as long as the P wave stayed
within the extended postventricular atrial refractory period, no ventricular
extrasystole disrupted the sequence, and the R-R interval of spontaneous beats
was shorter than the extended atrial escape interval. Such a pacemaker response
should not be misinterpreted as device malfunction.
PMID- 10192863
TI - Successful radiofrequency ablation of a slow atrioventricular nodal pathway on
the left posterior atrial septum.
AB - RF catheter ablation is highly effective in eliminating atrioventricular nodal
reentrant tachycardia by targeting the slow pathway in the posteroinferior part
of Koch's triangle in the right atrium. We report here a patient in whom "slow
fast" atrioventricular nodal reentrant tachycardia was eliminated only by
ablation of the slow pathway in the left atrial posteroseptal region at the level
of the mitral annulus after unsuccessful attempts at the traditional site on the
right side.
PMID- 10192864
TI - Failure of right atrial premature beats to reset atriofascicular tachycardia.
AB - A patient with a right atriofascicular (Mahaim) tachycardia was found to have
inducible antidromic supraventricular tachycardia, but atrial premature beats
from the right atrial free wall failed to reset the tachycardia. An interesting
transition from AV nodal reentry tachycardia to Mahaim tachycardia is also
presented.
PMID- 10192865
TI - Invasive ductal carcinoma of the male breast expanding from pacemaker pocket
decubitus.
AB - After twenty-five years of therapy with different unifocal pacemaking systems, an
84-year old male patient developed a nonseptic pacemaker decubitus. A rare
incidental finding of invasive ductal carcinoma of the right mammary gland was
surgically treated by a generous excision of the tumor and by consecutive
modified radical mastectomy. According to published literature, the association
of invasive ductal carcinoma arising from a pacemaker pocket decubitus and
followed by curative treatment has not been previously reported. We do conclude
that pacemaker generators in close relationship to the mammary gland should be
considered with suspicion.
PMID- 10192866
TI - Implantation of permanent dual chamber pacemaker in a pregnant woman by
transesophageal echocardiographic guidance.
AB - A 37-year-old woman complained of fatigue and dizziness because of intermittent
sinus arrest and asystole up to 5.2 seconds. She was 3 months into her pregnancy
and a dual chamber permanent pacemaker was implanted by transesophageal
echocardiographic guidance.
PMID- 10192867
TI - Pacemaker-induced superior vena cava obstruction: bypass using the intact azygous
vein.
AB - Superior vena cava thrombosis due to pacemaker leads is an uncommon but well
recognized complication. Its pathogenesis remains unclear and it is usually a
benign condition. Superior vena cava occlusion can be successfully treated by
thrombolysis and anticoagulation if the occlusion is recent, balloon venoplasty
and stenting, and surgery. We describe a case of superior vena cava obstruction
successfully bypassed using the intact native azygous vein, a technique that has
not been described before, with excellent long-term results.
PMID- 10192868
TI - Runaway pacemaker caused by a stuck accelerometer.
AB - We report a case of runaway pacemaker with a ventricular pacing rate of 190
beats/min. The runaway occurred when the accelerometer became stuck due to the
magnet application during VVIR pacing. Runaways in modern pacemakers are
particularly rare, but they do still occur. The best solution for this phenomenon
is generator replacement.
PMID- 10192869
TI - Risk of interference between pacemakers and security systems.
PMID- 10192870
TI - SPICED TEAS manuscript. Study of Pacemaker and Implantable CardiovErter
Defibrillator Triggering by Electronic Article Surveillance devices.
PMID- 10192871
TI - Study of Pacemaker and Implantable CardiovErter Defibrillator Triggering by
Electronic Article Surveillance devices (SPICED TEAS)
PMID- 10192872
TI - Electronic article surveillance (EAS) systems.
PMID- 10192873
TI - Pacemaker/ICD patients and the electromagnetic environment.
PMID- 10192874
TI - Multiple myeloma. A model of nature.
PMID- 10192875
TI - B cell maturation in relation to multiple myeloma.
AB - Maturation of a normal B-cell precursor to a mature plasma cell involves
rearrangement and somatic mutation of the immunoglobulin variable (V) region
genes. These events occur at distinct stages of development, and when a B cell
undergoes neoplastic transformation, the genetic imprint reflects the clonal
history of the cell of origin. Sequence analysis of V-genes can reveal bias as
compared with the available repertoire, possibly reflecting a role for
superantigen in stimulation of certain B cells. It can also indicate if the
tumour cell has encountered the site of somatic mutation in the germinal centre,
and if this mechanism is still active post-transformation. Analysis may also
reveal a potential influence of persistent antigen in driving tumour growth.
Genetic evidence supports the concept that tumour cells are not frozen at a
single point of differentiation, but are able to move through certain limited
stages. For myeloma, V-gene analysis indicates that the malignant cell population
is likely to be derived from an antigen-selected plasma cell, but that a less
mature minor B cell population of identical sequence may coexist. In contrast,
benign plasma cell tumours can include B cells still undergoing somatic mutation.
In both malignant and benign disease, transcripts of clonally-related alternative
isotypes have been identified V-gene analysis is contributing to the diagnosis,
monitoring and understanding of B-cell tumours, and may facilitate the
development of rational approaches to therapy.
PMID- 10192876
TI - Homing mechanisms of myeloma cells.
AB - A stricking feature of myeloma plasma cells concerns their tendency to reside in
the bone marrow compartment during the main course of the disease evolution. This
micro-environment provides the appropriate signals for growth and survival of the
tumor cells. Since small amounts of myeloma cells are also detectable in the
peripheral blood, it can be assumed that these cells represent lymph node and/or
bone marrow derived tumor cells that directly contribute to disease spreading.
The detection of such myeloma-related cells in the circulation implicates that
they must be equipped with the appropriate surface molecules that mediate binding
to endothelium, responsiveness to chemokines, transendothelial migration and
extravasation. The specificity of this migration process might be a second
important factor that determines the selective homing of myeloma cells in the
marrow-microenvironment. During the end phase of the disease, increasing numbers
of myeloma cells become detectable in the blood circulation and also
extramedulary tumor localisation at other sites (liver, lung, ascites and pleural
fluid) can occur. Molecular evolution towards stroma-independency in association
with an enhanced extravasation potential are likely to be the key mechanisms that
underlie this disturbed homing behaviour.
PMID- 10192877
TI - Multiple myeloma and related disorders. Lessons from an animal model.
AB - This short review of our own work presents two aspects of the studies on multiple
myeloma (MM) in an animal model--the aging C57BL/KaLwRij mouse: 1. the
immunological/biological aspect of the development of monoclonal B-cell
proliferative disorders, the so-called monoclonal gammopathies (MG), and 2. the
use of the mouse myeloma of the 5TMM lines for studies on the
etiology/pathogenesis of MM and for developing new ways of treatment of this
disease. Our research revealed that there are at least four major mechanisms in
the development of MG. Many of the results were confirmed in clinical studies and
lead to a new classification of MG according to their biology and possible
pathogenesis. Most of MG can be classified into one of the following categories:
1. B-cell malignancies, 2. B-cell benign neoplasia, 3. MG due to an
immunodeficiency with T/B cell imbalance, and 4. Antigen driven MG.
PMID- 10192878
TI - HHV-8 and multiple myeloma.
AB - Recently, a new member of the gamma-herpesvirus family, human herpesvirus 8 (HHV
8), was identified in a case of Kaposi's sarcoma. This virus has also been found
in the nonmalignant dendritic cells of the bone marrow from myeloma patients. In
addition, HHV-8 is also detectable in the peripheral blood of most patients
although its absence suggests earlier stage disease. By contrast, this virus is
undetectable in the blood of family members and sexual partners of myeloma
patients. Sequencing of HHV-8 open reading frames from myeloma patients show
interpatient differences as well as consistent differences in the myeloma samples
compared to HHV-8 in other malignancies associated with HHV-8 infection.
Consistent expression of both the viral homologues of interferon regulatory
factor and IL-8 receptor suggest a possible role for these transforming viral
genes in the pathogenesis of myeloma. The latter gene is known to induce
angiogenesis and preliminary studies show the abundance of vascular endothelial
cells in the bone marrow of myeloma patients.
PMID- 10192880
TI - Ig gene sequences in the study of clonality.
AB - Investigations of normal and neoplastic B cells are being channelled into new
directions by recent work on immunoglobulin variable region genes. Assembling of
heavy and light chain genes introduces enormous heterogeneity into the third
complementarity determining regions (CDR3s) of immunoglobulins. For reasons that
will become apparent below, variation in CDR3s is especially broad in heavy
chains. Moreover, antigen-driven somatic mutations introduce another layer of
permutations in antibody structures during the immune response. These
diversifying mechanisms have interesting clinical applications. Our understanding
of the clonal origins of malignant B cells has been improved by analysis of V
gene structures in leukemias, B-cell lymphomas and multiple myelomas. Detection
of very small populations of malignant clones within a larger population of
normal B cells is now possible with the cell-specific markers encoded by the
unique V gene sequences of the CDR3. In this report I will try to give an
overview of how the immunoglobulin repertoire is being generated, how the
immunoglobulin genes can be analysed and sequenced, what the clinical
applications are for multiple myeloma and I will speculate a little bit about
what the future might bring.
PMID- 10192879
TI - Immunophenotypic and DNA content characteristics of plasma cells in multiple
myeloma and monoclonal gammopathy of undetermined significance.
AB - In the present paper we review the immunophenotypic characteristics of plasma
cells (PC) and the PC DNA contents from multiple myeloma (MM) and monoclonal
gammopathy of undetermined significance (MGUS), and its value for the
differential diagnosis between both entities. The strong reactivity for CD38 and
the positivity for CD138 are the two best markers for identifying PC. Myelomatous
PC display an heterogeneous phenotype consistent with the fact that the
neoplastic clone is able to undergo a certain degree of differentiation. In
addition, PC from MM patients usually lack surface expression of B-cell
associated antigens and frequently display reactivity for markers which are not
restricted to the B-cell lineage. In MGUS patients, two clearly defined and
distinct PC subpopulations can be identified. One of these PC subpopulations
shows phenotypic characteristics identical to those of normal PC, including a
very strong reactivity for the CD38 antigen, intermediate/low light scatter
characteristics and positivity for CD19, in the absence of CD56, and corresponds
to the residual normal bone marrow PC. The second PC subpopulation shows an
immunophenotype similar to that of myelomatous PC, characterized by a slightly
lower reactivity for CD38 and strong CD56 expression, on the absence of
positivity for CD19, these PC corresponding to the clonal counterpart. Using a
simultaneous staining for PC and DNA, around 60% of MM and 73% of MGUS patients
display DNA aneuploidy, the majority of them being hyperdiploid. However, in
contrast to MM patients, in MGUS patients two clearly different PC subsets can be
discriminated in most cases (73%): a diploid and an aneuploid (hyperdiploid)
subset, corresponding to normal and clonal PC, respectively. Upon comparing
hyperdiploid with diploid patients in MM, the former display a better prognosis,
in line with the higher incidence of DNA hyperdiploidy in MGUS. A clear
correlation between the percentage of S-phase PC and several prognosis features
of MM has been found. In spite of these findings, no significant differences in
the percentage of pathological S-phase PC are detected between MM and MGUS
patients. Regarding the differential diagnosis between MGUS and MM, multivariate
analysis shows that the ratio between the number of clonal and normal residual PC
is the best single parameter.
PMID- 10192881
TI - Clinical aspects of multiple myeloma and related disorders including amyloidosis.
AB - Multiple myeloma is characterized by the presence of bone pain, weakness, and
fatigue. Ninety-eight percent of patients have an M-protein in the serum or urine
at the time of diagnosis. Skeletal roentgenograms are abnormal in nearly 80%.
Renal insufficiency (creatinine > or = 2 mg/dL) is present in one-fourth. The
major causes of renal insufficiency are "myeloma kidney" and hypercalcemia. The
diagnosis of multiple myeloma depends upon the presence of more than 10% plasma
cells or a plasmacytoma plus an M-protein in the serum or urine or lytic bone
lesions. Multiple myeloma must be differentiated from monoclonal gammopathy of
undetermined significance and smoldering multiple myeloma. The plasma cell
labeling index and the presence of circulating plasma cells in the peripheral
blood are helpful in the differential diagnosis. Plasma cell leukemia,
osteosclerotic myeloma (POEMS syndrome), and plasmacytomas are discussed. The
heavy-chain diseases consist of alpha, gamma, and mu heavy-chain disease. The
fibrils of primary amyloidosis consist of kappa or lambda monoclonal light
chains. Weakness, fatigue, and weight loss are the most frequent symptoms.
Macroglossia occurs in 10%. An M-protein is found in the serum or urine in 90%.
The presence of nephrotic syndrome, renal insufficiency, congestive heart
failure, orthostatic hypotension, or sensorimotor peripheral neuropathy, and an M
protein in the serum or urine suggest the possibility of primary amyloidosis. The
diagnosis depends upon the demonstration of amyloid in tissues. The subcutaneous
fat aspirate is positive in 80% while the bone marrow is positive in 55%. If
these tissues are negative, one should obtain tissue from an involved organ.
PMID- 10192882
TI - Clinical significance of bone marrow biopsy and plasma cell morphology in MM and
MGUS.
AB - Multiple myeloma (MM) is characterized by plasma cell infiltration in the bone
marrow, suppression of normal haematopoiesis, destruction of bone, renal failure
and recurrent infections. The extent of organ involvement, severity of
complications, drug sensitivity and therefore the clinical course differ widely
among patients. Specific and reliable laboratory examinations and especially
morphology including both biopsy and aspirations are required to evaluate its
aggressivity and extent. In this review of MM and its variants we emphasize the
impact of morphology on the diagnostic and prognostic approach to MM and MGUS,
and on the planning and monitoring of appropriate therapy.
PMID- 10192883
TI - Conventional chemotherapy in multiple myeloma.
AB - Multiple myeloma is a disease, mainly affecting elderly individuals, for which no
curative therapy is available today. The most important aim of the treatment
given to such patients should therefore be to improve the quality of life and
prolong the period of non-progressive disease. A concise review is given of the
therapeutic options in patients, for whom high-dose cytostatic therapy with stem
cell support is not an alternative. Traditional intermittent courses of melphalan
and prednisone still holds its role as standard induction therapy. This regimen
has convincingly in a recent large world-wide overview been shown to be able to
induce a length of overall and progression-free survival, that is comparable to
what can be achieved with different forms of combination chemotherapy. For
patients refractory to alkylating agents a combination of vincristine,
doxorubicin and prednisone (VAD) or intermittent courses of high-dose steroids
alone are well proven alternatives. Several new drugs are under evaluation, but
their therapeutic role is not yet established.
PMID- 10192884
TI - The role of alpha-interferon in multiple myeloma.
AB - Alpha-interferon (Ifn-alpha) has anti-tumor activity in vivo when used as a
single agent in multiple myeloma (MM). However, the mechanisms responsible for
this activity have not been clarified so far. Ifn-alpha has been therapeutically
tested in a number of clinical trials for remission induction, maintenance
therapy, and in different combinations with chemotherapy or steroids. The results
of these trials are partially controversial and do not undoubtedly support Ifn
alpha treatment in any of these indications. However, meta-analyses using
individual patient data or published results of the trials revealed small but
significant advantages for MM patients treated with Ifn-alpha monotherapy for
maintenance or in combination with conventional chemotherapy for remission
induction. These advantages weigh against reduction of quality of life due to
adverse effects commonly seen in Ifn-alpha treated MM patients and in addition
relatively high treatment costs. Future efforts should be made to find prognostic
factors determining effectiveness of Ifn-alpha therapy. Furthermore, the outcome
of Ifn-alpha treatment should be improved by new therapy strategies based on a
better understanding of the pathophysiological mechanisms influenced by Ifn-alpha
in MM.
PMID- 10192885
TI - Bisphosphonates in multiple myeloma.
AB - Bone disease is a frequent manifestation of multiple myeloma, and results in
considerable morbidity. In this review we summarise the current theories as to
the mechanism of bony destruction in this disease and discuss the
interrelationships between the malignant plasma cells and those cells responsible
for bone remodelling, i.e. the osteoclasts and osteoblasts. The bisphosphonates
are a long established group of drugs known to have inhibitory effects on
osteoclast activity, and in common use for osteoporosis and Paget's disease.
Their role in myeloma is less clear. Several clinical studies, including phase
III randomised placebo controlled trials, have been reported in recent years.
Although these have tended to show a benefit for bisphosphonate treatment, we
have not yet identified the most appropriate use of these agents. Two of the
clinical trials have suggested that bisphosphonates may also have a beneficial
effect on the underlying disease, a tantalizing theory which has been supported
with some early laboratory data.
PMID- 10192886
TI - Drug resistance in multiple myeloma.
AB - Multidrug resistance (MDR) is a pleiotropic resistance against several unrelated
drugs. It may be induced by prolonged exposure of cells to drugs such as
doxorubicin, etoposide and vinca alkaloids. Once MDR develops in clinical tumors,
it is a major obstacle for the improvement of treatment of multiple myeloma (MM).
Several specific mechanisms have been identified in clinical refractory MM
patients including typical MDR, which is associated with P-glycoprotein (Pgp) and
Lung Resistance Protein (LRP). The expression of the proteins associated with
these genes seems to depend on exposure to chemotherapeutic agents. Recently,
reversal of MDR by non-cytotoxic agents such as verapamil, cyclosporin A and PSC
833 (Valdospar) was explored in acute leukemia and multiple myeloma. Preliminary
results from clinical phase I/II trials indicate that reversal of MDR is possible
and that it may lead to alterations of the plasma pharmacokinetics of the
cytostatic agents, in addition to P-glycoprotein inhibition in tumor cells. The
potential implications of P-glycoprotein reversal are discussed.
PMID- 10192887
TI - Allogeneic bone marrow transplantation in multiple myeloma.
AB - Allogeneic transplantation in multiple myeloma can induce complete remission,
defined as disappearance of abnormal immunoglobulins in the blood, light chains
in the urine and no apparent myeloma cells in the marrow, in about 50 percent of
patients. The five-year survival is about 30 percent and important prognostic
factors for survival are to be a female, to be in stage I at the time of
diagnosis irrespective of the time of transplantation, to have received only one
line of treatment before transplantation, to have responsive disease and a low
beta 2-microglobulin. Transplant-related mortality is between 40-50 percent, and
therefore overall survival is poorer than with autologous transplantation, while
long-term survival is similar with both transplant modalities. Although the
relapse rate of patients in complete remission is about 50 percent at 5 years, it
is still lower than with autologous transplantation. Donor lymphocyte transfusion
to patients with persistent abnormal immunoglobulins or relapse may induce
regression or new complete remissions. Further studies aim at reducing transplant
related mortality by using peripheral blood stem cells, CD34-selected cells, more
aggressive anti-bacterial, anti-fungal and anti-viral treatment and relapse rate
will be counteracted by donor lymphocyte transfusions and perhaps post-transplant
interferon treatment.
PMID- 10192888
TI - Therapeutic strategies and controversies in the treatment of multiple myeloma.
AB - This is a general overview on the treatment of multiple myeloma (MM) with
particular emphasis on controversial aspects. The importance of avoiding
treatment for asymptomatic patients is emphasized. The selection of initial
treatment (melphalan/prednisone vs. combination chemotherapy) is summarized. The
duration of initial treatment, the role of interferon maintenance, as well as the
treatment of resistant myeloma patients are critically reviewed. Finally, the
treatment of particular subsets of myeloma patients (i.e., young patients,
elderly people, patients presenting with renal failure) is discussed.
PMID- 10192889
TI - The role of autologous stem cell transplantation in the management of multiple
myeloma.
AB - In the past 10 years, the concept of dose intensity with autologous hematopoietic
stem cell support has modified the treatment of patients with multiple myeloma
(MM). We review here the rationale for high dose therapy (HDT) and autologous
stem cell transplantation (ASCT) in the treatment of myeloma patients, its
benefit as compared to standard therapy, indications according to patients' age
and clinical status, modalities and optimal timing. We also discuss the future
prospects for improvement.
PMID- 10192890
TI - Intensive therapy in multiple myeloma.
AB - During the past 10 years, high-dose therapy (HDT) has been widely explored in
multiple myeloma. The first randomized study comparing conventional chemotherapy
and HDT followed by autologous bone marrow transplantation has been completed by
the Intergroupe Francais du Myelome. This trial designed for patients under 65
years of age with newly diagnosed myeloma has shown that HDT is superior to CC in
terms of response rate, event free survival and survival. However a number of
issues remain to be addressed regarding autologous transplantation: feasibility
and survival impact in patients over 60 years of age, conditioning regimen,
source of stem cells, impact of tandem transplants, maintenance therapy. The
place of allogeneic bone marrow transplantation in the management of younger
patients remains controversial due to a high toxic death rate.
PMID- 10192891
TI - Active idiotype vaccination in multiple myeloma. GM-CSF may be an important
adjuvant cytokine.
AB - The idiotypic surface bound immunoglobulin structures on the myeloma cells can be
regarded as a tumor specific antigen. Naturally occurring humoral and cellular
immunity against the idiotype has been demonstrated. Idiotype immunization in
combination with GM-CSF induced a specific T cell response in all studied myeloma
patients (n = 5). The T cell response could be characterized as a type I response
(gamma-IFN production) which seemed preferentially to be MHC class I restricted.
Patients with a low tumor burden might be those which most favourably respond to
this kind of therapeutic intervention.
PMID- 10192892
TI - Bcl-2 antisense therapy in multiple myeloma.
AB - Multiple myeloma is a plasma cell tumor localised in the bone marrow. During
chemotherapy drug resistance develops in almost all patients. We have indications
that the anti-apoptopic protein Bcl-2 is a key element in multi drug resistance
in myeloma. Reduction of Bcl-2 renders the tumor cell susceptible to drug induced
apoptosis. This suggests that therapies directed at lowering Bcl-2 levels in
myeloma cells in vivo, like Bcl-2 antisense treatment, might chemosensitize the
tumor cells and therefore might be applicable for therapeutic use.
PMID- 10192893
TI - Intrinsic capacities of soil microflorae for gasoline degradation.
AB - A methodology to determine the intrinsic capacities of a microflora to degrade
gasoline was developed, in particular for assessing the potential of autochtonous
populations of polluted and non polluted soils for natural attenuation and
engineered bioremediation. A model mixture (GM23) constituted of the 23 most
representative hydrocarbons of a commercial gasoline was used. The capacities of
the microflorae (kinetics and extent of biodegradation) were assessed by
chromatographic analysis of hydrocarbon consumption and of CO2 production. The
degradation of the components of GM23 was assayed in separate incubations of each
component and in the complete mixture. For the microflora of an unpolluted spruce
forest soil, all hydrocarbons of GM23 except cyclohexane, 2,2,4- and 2,3,4
trimethylpentane isomers were degraded to below detection limit in 28 days. This
microflora was reinforced with two mixed microbial communities selected from
gasoline-polluted sites and shown to degrade cyclohexane and 2,2,4
trimethylpentane. With the reinforced microflora, complete degradation of GM23
was observed. The degradation patterns of individual components of GM23 were
similar when the compounds were present individually or in the GM23 mixture, as
long as the concentrations of 2-ethyltoluene and trimethylbenzene isomers were
kept sufficiently low (< or = 35 mg.l-1) to remain below their inhibitory level.
PMID- 10192894
TI - Availability of phosphorus and sulfur of insecticide origin by fungi.
AB - Thirteen fungal species isolated from soil treated with pesticides were tested
for their ability to mineralize and degrade three organophosphate insecticides
currently used in Egypt (Cyolan, Malathion and Dursban) in liquid media free from
phosphorus (P) and sulfur (S). All fungal species grew successfully on the
culture media treated with the three used doses of insecticides (10, 50 and 100
ppm active ingredient) but the growth rate varied with the species, the
insecticide and the doses. At 10 ppm level, insecticide degradation expressed in
term of organic P mineralization (calculated as % of applied P) was the highest
with all fungi tested. Organic P mineralization from pesticides was decreased by
increasing the dose used to 50 and 100 ppm. The highest amount of P mineralized
was observed with Cyolan followed by Malathion whilst P mineralization from
Dursban proceeded very slowly. Aspergillus terreus showed the greatest potential
to mineralize organic P followed by A. tamarii, A. niger, Trichoderma harzianum
and Penicillium brevicompactum whilst the remaining fungi only moderately
mineralized the organic P component of the insecticides tested. Organic sulfur
mineralization by the used fungal species paralleled, to some extent, organic P
mineralization. The extracellular protein content of culture filtrates in the
presence of various doses of insecticides was also decreased by increasing
insecticide concentrations. The extracellular protein was significantly
correlated with P and S mineralization (r = 0.89** and 0.64**, respectively)
whilst correlation with cell dry mass was not significant (r = 0.03 and 0.003)
suggesting a direct relationship between pesticide degradation and microbial
protein production. The addition of P or S to the growth media enhanced
extracellular protein excretion, and increased organic P and S mineralization by
the most potent species tested (A. niger, A. tamarii, A. terreus and T.
harzianum). This increment was significant in most cases, especially at the
higher application rates. The relationship between extracellular protein
excretion and organic P and S mineralization from insecticides was highly
significant with the addition of inorganic phosphorus (r = 0.96** and 0.83**,
respectively) or sulfur (r = 0.85** and 0.89**, respectively) to the growth
media.
PMID- 10192895
TI - Degradation of pinene by Bacillus pallidus BR425.
AB - An aerobic thermophile has been isolated from an alpha-pinene enrichment culture.
The isolate, which was designated BR425, has been tentatively identified as
Bacillus pallidus using 16S ribosomal RNA gene sequencing and organism
morphology. Monophasic and biphasic incubations of BR425 cells with alpha-pinene,
beta-pinene, and limonene yielded a number of oxidized monoterpene metabolites
with carveol as a common metabolite. A pinene degradation pathway with carveol
and carvone as central metabolic intermediates is suggested.
PMID- 10192896
TI - Microbial degradation of tannins--a current perspective.
AB - Tannins are water-soluble polyphenolic compounds having wide prevalence in
plants. Hydrolysable and condensed tannins are the two major classes of tannins.
These compounds have a range of effects on various organisms--from toxic effects
on animals to growth inhibition of microorganisms. Some microbes are, however,
resistant to tannins, and have developed various mechanisms and pathways for
tannin degradation in their natural milieu. The microbial degradation of
condensed tannins is, however, less than hydrolysable tannins in both aerobic and
anaerobic environments. A number of microbes have also been isolated from the
gastrointestinal tract of animals, which have the ability to break tannin-protein
complexes and degrade tannins, especially hydrolysable tannins. Tannase, a key
enzyme in the degradation of hydrolysable tannins, is present in a diverse group
of microorganisms, including rumen bacteria. This enzyme is being increasingly
used in a number of processes. Presently, there is a need for increased
understanding of the biodegradation of condensed tannins, particularly in
ruminants.
PMID- 10192897
TI - Effect of calcium on the surfactant tolerance of a fluoranthene degrading
bacterium.
AB - Surfactants are known to increase the apparent aqueous solubility of polycyclic
aromatic hydrocarbons (PAHs) and may thus be used to enhance the bioavailability
and thereby to stimulate the biodegradation of these hydrophobic compounds.
However, surfactants may in some cases reduce or inhibit biodegradation because
of toxicity to the bacteria. In this study, toxicity of surfactants on
Sphingomonas paucimobilis strain EPA505 and the effect on fluoranthene
mineralization were investigated using Triton X-100 as model surfactant. The data
showed that amendment with 0.48 mM (0.3 g l-1) of Triton X-100 completely
inhibited fluoranthene and glucose mineralization and reduced cell culturability
by 100% in 24 h. Electron micrographs indicate that Triton X-100 adversely
affects the functioning of the cytoplasmic membrane. However, in the presence of
4.13 mM Ca(2+)-ions, Triton X-100 more than doubled the maximum fluoranthene
mineralization rate and cell culturability was reduced by only 10%. In liquid
cultures divalent ions, Ca2+ in particular and Mg2+ to a lesser extent, were thus
shown to be essential for the surfactant-enhanced biodegradation of fluoranthene.
Most likely the Ca(2+)-ions stabilized the cell membrane, making the cell less
sensitive to Triton X-100. This is the first report on a specific factor which is
important for successful surfactant-enhanced biodegradation of PAHs.
PMID- 10192898
TI - Influence of selected physical parameters on the biodegradation of acrylamide by
immobilized cells of Rhodococcus sp.
AB - The influences of concentration of acrylamide, pH, temperature, duration of
storage of encapsulated cells and presence of different metals and chelators on
the ability of immobilized cells of a Rhodococcus sp. to degrade acrylamide were
evaluated. Immobilized cells (3 g) rapidly degraded 64 and 128 mM acrylamide in 3
and 5 h, respectively, whereas free cells took more than 24 h to degrade 64 mM
acrylamide. An acrylamide concentration of 128 mM inhibited the growth of the
free cells. Immobilized bacteria were slow to degrade acrylamide at 10 degrees C.
Less than 60% of acrylamide was degraded in 4 h. However, 100% of the compound
was degraded in less than 3 h at 28 degrees C and 45 degrees C. The optimum pH
for the degradation of acrylamide by encapsulated cells was pH 7.0. Less than 10%
of acrylamide was degraded at pH 6.0, while ca. 60% of acrylamide was degraded at
pH 8.0 and 8.5. Copper and nickel inhibited the degradation, suggesting the
presence of sulfhydryl (-SH) groups in the active sites of the acrylamide
degrading amidase. Iron enhanced the rates of degradation and chelators (EDTA and
1,10 phenanthroline) reduced the rates of degradation suggesting the involvement
of iron in its active site(s) of the acrylamide-degrading-amidase. Immobilized
cells could be stored up to 10 days without any detectable loss of acrylamide
degrading activity.
PMID- 10192899
TI - Kinematic construction of the trajectory of sequential arm movements.
AB - A kinematic construction rule determining the trajectory of human sequential
movements is formulated using minimum-jerk and minimum-angular-jerk trajectories.
The kinematic construction rule states that the observed trajectory of sequential
movements coincides with a weighted average of the minimum-jerk trajectory and
the segmented minimum-angular-jerk trajectory. This rule covers not only point-to
point movements but also simple sequential movements. Five kinds of experiments
that measure the trajectories in planar, multijoint sequential arm movements were
conducted. The measured trajectories coincide with the predictions made on the
basis of the kinematic construction rule presented here. Moreover, predictions of
previous models such as the minimum-jerk, the equilibrium-trajectory, and the
minimum-torque-change models are shown to be incompatible with our observations
of sequential movements.
PMID- 10192900
TI - An architectural hypothesis for direction selectivity in the visual cortex: the
role of spatially asymmetric intracortical inhibition.
AB - Within a linear field approach, an architectural model for simple cell direction
selectivity in the visual cortex is proposed. The origin of direction selectivity
is related to recurrent intracortical interactions with a spatially asymmetric
character along the axis of stimulus motion. No explicit asymmetric temporal
mechanisms are introduced or adopted. The analytical investigation of network
behavior, carried out under the assumption of a linear superposition of
geniculate and intracortical contributions, shows that motion sensitivity of the
resulting receptive fields emerges as a dynamic property of the cortical network
without any feed-forward direction selectivity bias. A detailed analysis of the
effects of the architectural characteristics of the cortical network on
directionality and velocity-response curves was conducted by systematically
varying the model's parameters.
PMID- 10192901
TI - Distortions of length perception.
AB - A combined influence of stimulus orientation and structure on the judgment of
length was tested in psychophysiological experiments. The subjects adjusted the
test part of a stimulus to be equal in length to the reference part. The
orientation of the parts of the stimulus varied in the experiments. The stimuli
(three dots or the Oppel-Kundt figure, which had ten dots within the filled part)
were generated on the monitor. In the Oppel-Kundt figure, the filled part was
considered as a reference and the empty part as a test. In sessions of the
experiments, values of errors were measured as functions of the size and
orientation of the stimulus. The reference part length varied within 14-150 min
are range, and the orientation was fixed in 0 degree, 90 degrees, 180 degrees or
270 degrees positions. The orientation of the test part varied from 0 degree to
360 degrees in 7 degrees steps. We assume, that the experiments with the three
dot stimuli yielded pure characteristics of visual field anisotropy, while those
with the Oppel-Kundt figure showed the combined effect of both the components
(anisotropy and spatial filtering). The data demonstrated independence of the two
factors from each other in a simultaneous manifestation. The characteristics of a
pure Oppel-Kundt illusion have been found to be in close correspondence with the
predictions of the model of spatial filtering.
PMID- 10192902
TI - Reconstruction of equilibrium trajectories during whole-body movements.
AB - The framework of the equilibrium-point hypothesis was used to reconstruct
equilibrium trajectories (ETs) of the ankle, hip and body center of mass during
quick voluntary hip flexions ('Japanese courtesy bow') by standing subjects.
Different spring loads applied to the subject's back were used to introduce
smooth perturbations that are necessary to reconstruct ETs based on a series of
trials at the same task. Time patterns of muscle torques were calculated using
inverse dynamics techniques. A second-order linear model was employed to
calculate the instantaneous position of the spring-like joint or center of mass
characteristic at different times during the movement. ETs of the joints and of
the center of mass had significantly different shapes from the actual
trajectories. Integral measures of electromyographic bursts of activity in
postural muscles demonstrated a relation to muscle length corresponding to the
equilibrium-point hypothesis.
PMID- 10192903
TI - Selective visual attention in a neurocomputational model of phase oscillators.
AB - In order to understand the dynamic property of covert selective visual attention,
which is different from the proposed mechanism of the spotlight metaphor, a two
layered network of phase oscillators was developed. The first layer is related to
the hippocampus and controls attention focus formation. The second layer is
related to the visual cortex, and each cortical oscillator in it simulates an
assembly of cells coding for a particular stimulus in the sense of feature
binding. Selective visual attention is interpreted as the result of the emergent
synchronization of hippocampus oscillators and a part of cortical oscillators.
Numerical experiments are presented to illustrate attention focus formation and
attention shifting from one set of stimuli to another. From a neurocomputational
point of view, our results demonstrate that attention is an emergent property of
the dynamical cell assemblies responding to the whole visual field.
PMID- 10192904
TI - Neural network models of bilateral coordination.
AB - Two mechanisms are described for controlling the movement of a pair of arms. The
first is an engineered motion planner that finds solutions to the ill-posed
problem of making noncolliding, goal-directed movements. The second uses neural
networks that learn to emulate the coordinated behaviors of the motion planner
using considerably less computational resources. Analysis of the networks shows
in general terms how they work, and allows us to make testable predictions about
some of the response properties that might be observed in the brain systems
serving bilateral coordination.
PMID- 10192905
TI - Molecular cloning and ethylene-inducible expression of Chib1 chitinase from
soybean (Glycine max (L.) Merr.).
AB - A soybean seed-specific PR-8 chitinase, named Chib2, has a markedly extended C
terminal segment compared to other plant Chib1 homologues of the PR-8 chitinase
family known to date. To further characterize the molecular structure and the
expression pattern of this chitinase family, we cloned two typical Chib1-similar
cDNAs (Chib1-1 and Chib1-2) from soybeans by PCR-cloning techniques. The deduced
primary sequence of Chib1-1 chitinase is composed of a signal peptide segment (26
amino acid residues) and a mature 273 amino acid sequence (calculated molecular
mass 28,794, calculated pI 3.7). This Chib1-1 enzyme is more than 90% identical
to Chib1-2 chitinase but is below 50% identical to Chib2 enzyme. Thus, we
confirmed the occurrence of two distinct classes, Chib1 and Chib2 in the plant PR
8 chitinase family. The Chib1 genes, interrupted by one intron, were found to be
up-regulated in response to ethylene in stems and leaves, but scarcely expressed
in developing soybean seeds. Chib1 chitinases may be responsible for protecting
the plant body from various pathogenic attacks.
PMID- 10192906
TI - Gene cloning and overexpression of a geranylgeranyl diphosphate synthase of an
extremely thermophilic bacterium, Thermus thermophilus.
AB - A geranylgeranyl diphosphate (GGPP) synthase gene of an extremely thermophilic
bacterium, Thermus thermophilus, was cloned and sequenced. T. thermophilus GGPP
synthase, overexpressed in Escherichia coli cells as a glutathione S-transferase
fusion protein, was purified and characterized. The fusion protein, retaining
thermostability, formed a homodimer, and showed higher specific activity than did
a partially purified thermostable enzyme previously reported. Optimal reaction
conditions and kinetic parameters were also examined. The deduced amino acid
sequence indicated that T. thermophilus GGPP synthase was excluded from the group
of bacterial type GGPP synthases and lacked the insertion amino acid residues in
the first aspartate-rich motif as do archaeal and eukaryotic short-chain
prenyltransferases.
PMID- 10192907
TI - cAMP-mediated catabolite repression and electrochemical potential-dependent
production of an extracellular amylase in Vibrio alginolyticus.
AB - Vibrio alginolyticus, a halophilic marine bacterium, produced an extracellular
amylase with a molecular mass of approximately 56,000, and the amylase appeared
to be subject to catabolite repression mediated by cAMP. The production of
amylase at pH 6.5, at which the respiratory chain-linked H+ pump functions, was
inhibited about 75% at 24 hours following the addition of 2 microM carbonyl
cyanide m-chlorophenylhydrazone (CCCP), while the production at pH 8.5, at which
the respiratory chain-linked Na+ pump functions, was only slightly inhibited by
the addition of 2 microM CCCP. In contrast, the production of amylase in a mutant
bacterium defective in the Na+ pump was almost completely inhibited even at pH
8.5 as well as pH 6.5 by the addition of 2 microM CCCP.
PMID- 10192908
TI - Promotion of antibiotic production by high ethanol, high NaCl concentration, or
heat shock in Pseudomonas fluorescens S272.
AB - A stress imposed by a continuous feed of high ethanol, high NaCl concentration,
or a high temperature shock increased antibiotic production by several times in
Pseudomonas fluorescens S272. A tentative bioassay showed that the stress caused
about 40-fold elevation in the autoinducer activity. Addition of synthetic
autoinducers, N-(3-oxododecanoyl)-L-homoserine lactone or N-(3-oxohexanoyl)-L
homoserine lactone at a concentration of more than 100 micrograms/l to a non
stressed culture also increased the antibiotic production by several times. These
results suggested that the antibiotic production in P. fluorescens S272 was
regulated by N-acyl-homoserine lactone and the promotive effect by stress
occurred through any function that increased the autoinducer production.
PMID- 10192909
TI - Inhibitory effect of sulfur-containing compounds in Scorodocarpus borneensis
Becc. on the aggregation of rabbit platelets.
AB - The inhibitory effects of three pure compounds isolated from wood garlic, 2,4,5
trithiahexane (I), 2,4,5,7-tetrathiaoctane (II), and 2,4,5,7-tetrathiaoctane 2,2
dioxide (III), on rabbit platelet aggregation induced by collagen, arachidonic
acid, U46619, ADP (adenosine 5'-diphosphate), PAF (platelet aggregating factor),
and thrombin were studied in vitro. The anti-aggregating activity of 2,4,5,7
tetrathiaoctane 4,4-dioxide (IV) was also measured with collagen and arachidonic
acid. I, II, III, and IV inhibited the platelet aggregation induced by all tested
agonists. I, II, and III exhibited a stronger inhibitory effect against the
thrombin-induced aggregation of GFP (gel-filtered platelets) than against the
aggregation induced by the other agonists. Notably, the IC50 value for III was 4
microM, which is approximately 2.5 times stronger than MATS (methyl allyl
trisulfide), a major anti-platelet compound isolated from garlic. In inhibiting
collagen-induced aggregation, II was as potent as MATS and aspirin, with a marked
disaggregation effect on the secondary aggregation by arachidonic acid, at the
rate of 47.05%/min at a concentration of 10(-4) M. I, II, and III also suppressed
U46619-induced aggregation. These results suggest that sulfur-containing
compounds in wood garlic not only inhibit arachidonic acid metabolism but also
suppress aggregation in association with the function of the platelet plasma
membrane.
PMID- 10192910
TI - Molecular cloning and characterization of a cDNA for an iron-superoxide dismutase
in rice (Oryza sativa L.).
AB - We have isolated a cDNA encoding Fe-SOD from rice (Oryza sativa L.). The deduced
amino acid sequence consists of a polypeptide with 255 amino acids, including a
putative transit peptide (40 a.a.) in amino-terminal residues. This sequence is
similar to the known plant Fe-SODs but not classified in the group of known Fe
SODs. The metal analysis and SOD assays of the partial purified recombinant
protein expressed in E. coli showed that this cDNA encodes an iron-containing
SOD. However this SOD activity was not inhibited by the treatment with hydrogen
peroxide, which was expected to inhibit known Fe-SOD activity. mRNA of rice Fe
SOD was detected in all vegetative tissues examined, being especially abundant in
calli, and strongly increased by light induction. These results suggested that
this cDNA encodes rice Fe-SOD, which is apparently distinct from known plant Fe
SODs.
PMID- 10192911
TI - Concentration of serum lipids and aortic lesion size in female and male apo E
deficient mice fed docosahexaenoic acid.
AB - Apolipoprotein (apo) E-deficient mice were fed an atherogenic diet with either 1%
ethyl ester docosahexaenoic acid (DHA) or safflower oil (SO) as a source of
linoleic acid for 8 week. Both genders fed DHA had higher proportions of
eicosapentaenoic acid and DHA, and lower proportions of linoleic and arachidonic
acids in the liver and serum phospholipids than those fed SO. Males fed DHA had
greater liver weight and tended to have higher concentrations of serum lipids and
liver cholesterol than those fed SO, and there were opposite trends in females.
Dietary fats and gender led to no significant effect on lesion sizes in aortic
arch and thoracic plus abdominal aorta. These results indicate that the
interactive action of sex-related factor(s) with dietary polyunsaturated fatty
acids is involved in metabolic changes of serum lipids in apoE-deficient mice,
and addition of DHA, compared with addition of SO, is not effective to abolish
the atherosclerosis in this animal model.
PMID- 10192912
TI - Quality and safety evaluation of genetically engineered rice with soybean
glycinin: analyses of the grain composition and digestibility of glycinin in
transgenic rice.
AB - The composition of nutritionally and physiologically important molecules in
transgenic rice with the soybean glycinin gene was determined and compared with
that of a non-transgenic control. Except for the levels of protein, amino acids
and moisture, no marked differences were found between the two kinds of rice. The
protein content of the transgenic rice was about 20% higher than the control
(control, 6.5 g/100 g; transgenic, 8.0 g/100 g) with a concomitantly lower
moisture content. This increased protein content mainly resulted from the
increased glycinin expressed in the transgenic rice, and the protein was
susceptible to gastric and intestinal digestion juices. In parallel with the
increased protein content, some important amino acids lacking in quantity in
normal rice were replenished.
PMID- 10192913
TI - Effects of various kinds of dietary amino acids on the hepatotoxic action of D
galactosamine in rats.
AB - The protective effects of various kinds of dietary amino acids against the
hepatotoxic action of D-galactosamine (GalN) were examined. Male Wistar rats fed
with 20% casein diets containing 10% or 5% amino acid for one week were injected
with GalN (800 mg/kg body weight), and the serum aspartate aminotransferase
(AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH)
activities, the hepatic glycogen concentration, and the serum glucose-level were
examined 20 hours after the injection. In the groups with the 10% amino acid
diets, activities of AST, ALT, and LDH in serum of 10% L-glutamine (Gln), 10% L
asparagine (Asn), and 10% L-serine (Ser) groups were significantly lower than
those of the control group, and in the groups with the 5% amino acid diets, those
activities of 5% L-histidine (His), 5% L-tyrosine (Tyr), 5% L-lysine (Lys), and
5% L-glycine (Gly) groups were also lower than those of the control group. The
concentration of liver glycogen of 10% Gln-, 10% Asn-, and 10% Ser- groups and
those levels of 5% His-, 5% Tyr-, 5% Lys-, and 5% Gly-groups were also
significantly higher than that of the control group. As a result, it was found
that some kinds of dietary amino acid such as L-Ser, L-Asn, L-His, L-Lys, L-Tyr,
and L-Gly, in addition to L-Gln were effective to protect the rats from GalN
induced injury.
PMID- 10192914
TI - Protective effect of flavonoids on endothelial cells against linoleic acid
hydroperoxide-induced toxicity.
AB - The protective effect of flavonoids against linoleic acid hydroperoxide (LOOH)
induced cytotoxicity was examined by using cultured endothelial cells. When the
cells were incubated with both LOOH and flavonoids, most flavonols protected the
cells from injury by LOOH. Flavones bearing an ortho-dihydroxy structure also
showed a protective effect against the cytotoxicity of LOOH. However, flavanones
had no effect. The structure-activity relationship revealed the presence of
either the ortho-di-hydroxy structure in the B ring of the flavonoids or 3
hydroxyl and 4-oxo groups in the C ring to be important for the protective
activities. The interaction between flavonoids and a-tocopherol was also examined
in this system. Flavonoids that were protective against LOOH-induced cytotoxicity
had at least an additive effect on the action of alpha-tocopherol against LOOH
induced damage.
PMID- 10192915
TI - Resolution and characterization of tryptophyl fluorescence of hen egg-white
lysozyme by quenching- and time-resolved spectroscopy.
AB - The fluorescence spectral distributions of four tryptophan residues of hen egg
white lysozyme were analyzed using time-resolved and quenching-resolved
fluorescence spectroscopy. Trp62 and Trp108 gave the fluorescence maxima at 352
nm and 342 nm, respectively. The fluorescence of Trp28 and Trp111 occurred only
at 300-360 nm and they were observed as an unresolved emission band with a
maximum and shoulder at 320 nm and 330 nm. The fluorescence quenching and decay
parameters of each tryptophan residue reconfirmed that Trp62 was fully exposed to
the solvent but Trp108 was sealed in the cage of the peptide chains and
furthermore showed that Trp28 and Trp111 are under the influence of the larger
fluctuational motion at the hydrophobic matrix box. The fluorescence responses of
each tryptophan residue to the lysozyme-ligand interaction suggested that the
internal fluctuation was reduced by the binding of ligand to give a distorted
conformation to the hydrophobic matrix box region.
PMID- 10192916
TI - Decrease in the levels of NGF and BDNF in brains of mice fed a tryptophan
deficient diet.
AB - The roles of dietary tryptophan (Trp) were evaluated in regulation of production
of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and
neurotrophin (NT)-3 in the various brain regions in ddY mice. Feeding the mice a
Trp-deficient diet for 2 weeks significantly decreased in the hippocampal level
of NGF but not those of BDNF and NT-3, as compared with feeding an adequate Trp
diet. The mice fed excess Trp did not have different levels of any of these
neurotrophins than in the mice fed an adequate Trp diet. The levels of BDNF in
the cerebral cortex were also significantly lower in the mice fed on a Trp
deficient diet, while the levels of NGF and NT-3 in the region were not modulated
upon feeding of the diet. The dietary Trp level had no significant effect on the
levels of NGF, BDNF, or NT-3 in the entorhinal cortex nor septum of the mice.
These results demonstrate that the brain levels of NGF and BDNF are dependent on
the dietary content of tryptophan.
PMID- 10192917
TI - Involvement of N-acetylcysteine-sensitive pathways in ricin-induced apoptotic
cell death in U937 cells.
AB - We have found that the antioxidant N-acetylcysteine (NAC) strongly inhibited
ricin-induced apoptotic cell death in U937 cells (human myeloid leukemia), as
judged by cytotoxicity, nuclear morphological change, and DNA fragmentation.
Consistent with these observations, a significant depletion of cellular
glutathione was observed in ricin-treated cells, and NAC prevented the decrease
in cellular glutathione. On the other hand, among the caspase inhibitors tested,
Z-Asp-CH2-DCB, which inhibited ricin cytotoxicity, also suppressed ricin-mediated
glutathione depletion, while NAC did not affect the generation of caspase-3 like
activity in ricin-treated cells. These results suggest that glutathione loss
takes place downstream from caspase activation during the ricin-induced apoptotic
process. Treatment with a specific inhibitor of glutathione biosynthesis,
buthionine sulfoximine (BSO) failed to induce apoptosis, and had no effect on the
overall extent of ricin-induced apoptosis, even though the glutathione level was
decreased to less than 5% of the control level. However, NAC still protected
against ricin-induced apoptosis in the BSO-treated cells. We conclude that
glutathione loss is one of several apoptotic changes caused by ricin, but is not
a sufficient factor for the progress of apoptosis. NAC may prevent ricin-induced
apoptosis through maintaining an intracellular reducing condition by acting as a
thiol supplier.
PMID- 10192918
TI - Identification of protein kinase B (PKB) as a phosphatidylinositol 3,4,5
trisphosphate binding protein in Dictyostelium discoideum.
AB - We have searched for phosphatidylinositol (PI)-3,4,5-trisphosphate (PIP3) binding
proteins in Dictyostelium discoideum using beads bearing a PIP3 analogue, PIP3
APB. One of the binding proteins with a molecular mass of 55 kDa was purified and
its amino acid sequence was partially analyzed. Database searches showed that the
analyzed sequence was identical to that of protein kinase B (PKB) of D.
discoideum. The specific activity of D. discoideum PKB, when expressed together
with constitutively active PI-3 kinase in mammalian cells, was elevated by about
three-fold, suggesting that PKB could also act downstream of PI-3 kinase in
Dictyostelium cells.
PMID- 10192919
TI - Immunopotentiating activity of nigerooligosaccharides for the T helper 1-like
immune response in mice.
AB - The immunopotentiating activity of nigerooligosaccharides (NOS), a mixture of
nigerose, nigerosyl glucose and nigerosyl maltose, was studied in vitro and in
vivo in mice. Mitogen-induced proliferation of splenocytes from normal mice was
augmented in a dose-dependent manner by nigerose of NOS. NOS enhanced interleukin
12 (IL-12) and interferon-gamma (IFN-gamma) production by normal splenocytes in
the presence of the potent IL-12 inducer, heat-killed Lactobacillus plantarum L
137, in vitro. Consistent with the in vitro finding, L. plantarum L-137-induced
IL-12 production and IL-2-induced IFN-gamma production were augmented in mice fed
with a 14.6% NOS diet for 2 weeks compared with mice fed with a control diet.
Notably, mice fed with the NOS diet showed significantly longer survival time
than the control mice after the induction of an endogenous infection by
administering 5-fluorouracil in a lethal dose. Taken together, these results
suggest that NOS may exert immunopotentiating activity through the activation of
an IL-12-dependent T helper 1-like immune response.
PMID- 10192920
TI - Induction of atherosclerosis in Brown Norway rats by immunization with ovalbumin.
AB - A study was carried out to establish an animal model that would be suitable for
evaluating the role of the diet in immune cell-mediated atherogenesis. Brown
Norway rats were initially treated with hypervitamin D2 for 4 days and then fed
on an atherogenic diet for 3 months, during which period the rats were either
immunized with ovalubumin plus Al(OH)3 (OVA group) or with Al(OH)3 alone (control
group) every 3 weeks. Aortic lesions were mainly composed of foam cells, the
lesions evaluated by the intimal thickness of the ascending aorta being more
severe in the OVA group than in the control group. The OVA group, in comparison
with the control group, showed prominently increased serum levels of OVA-specific
IgG and rat chymase, an indicator of mast cell degranulation. The intimal
thickness was positively correlated with the level of chymase. Immunization had
no effect on the serum lipid levels. These results support the hypothesis that
mast cells play a role in the early stage of atherosclerosis and suggest that
this animal model could be useful for evaluating the role of the diet in immune
related atherogenesis.
PMID- 10192921
TI - EnvZ-independent phosphotransfer signaling pathway of the OmpR-mediated
osmoregulatory expression of OmpC and OmpF in Escherichia coli.
AB - The Escherichia coli EnvZ-OmpR regulatory system is a paradigm of intracellular
signal transduction mediated by the well-documented phosphotransfer mechanism, by
which the expression of the major outer membrane proteins, OmpC and OmpF, is
regulated in response to the medium osmolarity. Although it is clear that the
EnvZ histidine(His)-kinase is the major player in the phosphorylation of OmpR, it
has been assumed for some time that there may be an alternative phospho-donor(s)
that can phosphorylate OmpR under certain in vitro and in vivo conditions. In
this study, to address this long-standing issue, extensive genetic studies were
done with certain mutant alleles, including delta envZ, delta(ackA-pta), and
delta sixA, as well as delta ompR. Here, for the first time, genetic evidence is
provided that, in addition to EnvZ, acetyl phosphate and an as yet unidentified
sensor His-kinase can serve as alternative in vivo phospho-donors for OmpR, even
in the envZ+ background. A model for the alternative phosphotransfer signaling
pathway involved in the phosphorylation of OmpR is proposed.
PMID- 10192923
TI - Methylation of tea catechins by rat liver homogenates.
AB - Methylation of (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECg), and (-)
epigallocatechin gallate (EGCg) was carried out with a rat liver homogenate and S
adenosyl-L-methionine. A structural analysis of the reaction products by MS and
NMR showed that 4'-O-methyl EGC, 4"-O-methyl ECg, and 4"-O-methyl EGCg had been
formed from EGC, ECg, and EGCg, respectively. These results suggest that
methylation may be one of the metabolic pathways to the catechins.
PMID- 10192922
TI - fcsA29 mutation is an allele of polA gene of Escherichia coli.
AB - The cold-sensitive fcsA29 mutation of Escherichia coli was found to be a new type
of cold-sensitive allele of the polA gene encoding DNA polymerase I, caused by an
Asp(116)-->Asn change in the 5'-->3' exonuclease domain. The fcsA29 mutant showed
typical polA mutant phenotypes such as UV sensitivity and unacceptability of recA
mutation. Cold-sensitive growth of the mutant was suppressed by introduction of a
sulA mutation, indicating that cell filamentation was due to the SOS response.
PMID- 10192925
TI - Possibility for discriminating between two representative non two-state thermal
unfolding models of proteins by DSC.
AB - Possible differences between two representative non two-state thermal unfolding
mechanisms of protein are discussed concerning differential scanning calorimetry.
Numerical simulations showed that, by DSC measurement, it is hard to discriminate
between the independent model, which assumes independent unfolding domains in a
protein, and the sequential model, which assumes intermediate(s) between native
and denatured states, especially when values of molecular weight, denaturation
enthalpy, and difference in denaturation temperature of each denaturation process
are large. DSC curve analysis of Aspergillus niger glucoamylase based on these
two models gave essentially the same thermodynamic parameters.
PMID- 10192924
TI - cDNA sequence and expression of a cold-responsive gene in Citrus unshiu.
AB - A cDNA clone encoding a protein (CuCOR19), the sequence of which is similar to
Poncirus COR19, of the dehydrin family was isolated from the epicarp of Citrus
unshiu. The molecular mass of the predicted protein was 18,980 daltons. CuCOR19
was highly hydrophilic and contained three repeating elements including Lys-rich
motifs. The gene expression in leaves increased by cold stress.
PMID- 10192926
TI - Comparison of precursor structures of the GGNG peptides derived from the
earthworm Eisenia foetida and the leech Hirudo nipponia.
AB - Earthworm and leech cDNAs encoding the GGNG peptides, a family of myotropic
peptides, were cloned and examined in this study. Both of the predicted precursor
proteins are of polyprotein structure and contain several putative peptides
distinct from the GGNG peptides. However, the precursors show organizations
distinct from each other and no sequence similarity except for the GGNG peptides.
PMID- 10192927
TI - Novel dolichyl derivatives in rat spleen.
AB - Novel dolichyl derivatives were found in rat spleen. The compounds were eluted
from reverse phase HPLC after eluting dolichyl fatty acid ester. The elution
profiles of the unsaponified forms of the unknown compounds were coincident with
that of dolichol from spleen on reverse phase HPLC. The compounds were not
dolichyl dolichoate, which are present in bovine thyroid. The compounds were not
found in young rats (4 months of age) but were found in old rats (above 12 months
of age), and they were not detected in other tissues under our conditions.
PMID- 10192928
TI - Sequence analysis of a 32-kb region including the major ribosomal protein gene
clusters from alkaliphilic Bacillus sp. strain C-125.
AB - Forty-one open reading frames (ORFs) were identified in a 32-kb DNA fragment of
alkaliphilic Bacillus sp. C-125. A similarity search using the BSORF database
found 37 ORFs with significant sequence similarity to B. subtilis RNA polymerase
subunits, elongation factor G, elongation factor Tu, and ribosomal proteins. Each
ORF product showed more than 70% identity to those of B. subtilis. Gene
organization in the region of str, S10, spc, and the alpha cluster was highly
conserved among three strains, C-125, B. subtilis, and B. stearothermophilus.
PMID- 10192929
TI - Synthesis of racemic 9-methyl-10-hexadecenoic acid.
AB - The marine bacterial fatty acid 9-methyl-10-hexadecenoic acid was conveniently
prepared in 6 steps and in a 22% overall yield, starting from commercially
available methyl 10-hydroxydecanoate. The naturally occurring fatty acid has the
E double bond configuration as confirmed by gas chromatographic co-elution
experiments.
PMID- 10192930
TI - Biophysical perturbations induced by ethylazinphos in lipid membranes.
AB - Perturbations induced by ethylazinphos on the physical organization of
dipalmitoylphosphatidylcholine (DPPC) and DPPC/cholesterol membranes were studied
by differential scanning calorimetry (DSC) and fluorescence polarization of 2-, 6
, 12-(9-anthroyloxy) stearic acids and 16-(9-anthroyloxy) palmitic acid.
Ethylazinphos (50 and 100 microM) increases the fluorescence polarization of the
probes, either in the gel or in the fluid phase of DPPC bilayers, and this
concentration dependent effect decreases from the surface to the bilayer core.
Additionally, the insecticide displaces the phase transition to a lower
temperature range and broadens the transition profile of DPPC. A shifting and
broadening of the phase transition is also observed by DSC. Furthermore at
insecticide/lipid molar ratios higher than 1/7, DSC thermograms, in addition to
the normal transition centered at 41 degrees C, also display a new phase
transition centered at 45.5 degrees C. The enthalpy of this new transition
increases with insecticide concentration, with a corresponding decrease of the
main transition enthalpy. Ethylazinphos in DPPC bilayers with low cholesterol (<
or = 20 mol%) perturbs the membrane organization as described above for pure
DPPC. However, cholesterol concentrations higher than 20 mol% prevent insecticide
interaction, as revealed by fluorescence polarization and DSC data. Apparently,
cholesterol significantly modulates insecticide interaction by competition for
similar distribution domains in the membrane. The present results strongly
support our previous hypothesis that ethylazinphos locates in the cooperativity
region, i.e. the region of C1-C9 atoms of the acyl chains, and extends to the
lipid-water interface, where it increases lipid packing order sensed across all
the thickness of the bilayer. Additionally, and, on the basis of DSC data, a
lateral regionalization of ethylazinphos is here tentatively suggested.
PMID- 10192931
TI - Solubilization of ubiquinone-10 in the lamellar and bicontinuous cubic phases of
aqueous monoolein.
AB - Using X-ray diffraction measurements and polarizing microscopy, the
solubilization of ubiquinone-10 (UQ10) was investigated in the lamellar and
reversed bicontinuous cubic phases of aqueous monoolein (MO, 86 wt% of
monooleoylglycerol). At 25 degrees C and UQ10 content below 0.5 wt%, a partial
phase diagram of the MO/UQ10/H2O system indicated the same sequence of hydration
induced phases as found in the MO/H2O system. This low amount of coenzyme had no
effect on the MO bilayer thickness and swelling behavior of phases, but it
promoted thermotropic Q230-->HII phase transition. We suggested that the effect
was determined by the UQ10 partitioning into the HII phase regions where the MO
chains must be stressed upon the phase transition. At UQ10 contents above 0.5
wt%, a solid 'UQ10-rich' phase appeared inside the initially homogeneous phases
within a few days. It was proposed that this process was driven by the coenzyme
lateral diffusion in the MO bilayer.
PMID- 10192932
TI - Interfacial binding of cutinase rather than its catalytic activity determines the
steady state interfacial tension during oil drop lipid hydrolysis.
AB - Hydrolysis of triglycerides by cutinase from Fusarium solani pisi causes in oil
drop tensiometer experiments a decrease of the interfacial tension. A series of
cutinase variants with amino acid substitutions at its molecular surface yielded
different values of the steady state interfacial tension. This tension value
poorly correlated with the specific activity as such nor with the total activity
(defined as the specific activity multiplied by the amount of enzyme bound) of
the cutinase variants. Moreover, it appeared that at activity levels above 15% of
that of wild type cutinase the contribution of hydrolysis to the decrease of the
tension is saturating. A clear positive correlation was found between the
interfacial tension plateau value and the interfacial binding of cutinase, as
determined with attenuated total reflection Fourier transformed infrared
spectroscopy (ATR-FTIR). These results indicate that the interfacial steady state
level is not determined by the rate of hydrolysis, but mainly by the interfacial
binding of cutinase.
PMID- 10192934
TI - Light scattering characterization of extruded lipid vesicles.
AB - By modeling extruded unilamellar lipid vesicles as thin-walled ellipsoidal
shells, mathematical analysis provides simple equations which relate the mean
elongation and other morphological characteristics of a vesicle population to
quantities readily obtained from combined static and dynamic light scattering
measurements. For SOPC vesicles extruded through a 100 nm pore-size filter into a
72.9 mM NaCl solution, the inferred elongation ratio (vesicle long axis to short
axis) is approximately 3.7 +/- 0.6. When these vesicles were dialyzed into
hypertonic or hypotonic solutions, this elongation ratio varied from 1 (for
spherical liposomes) in strongly hypotonic solutions to greater than 6 in
increasingly hypertonic solutions, beyond which abrupt morphological
transformations appear. These results are quantitatively consistent with a
mechanism of vesicle formation by extrusion and with the expectation that vesicle
volumes change to equalize internal and external osmolarity via water flow,
subject to the constraint of constant bilayer area. Our analysis also provides
simplified equations to assess the effects of vesicle elongation and
polydispersity on liposome parameters that are commonly required to characterize
vesicle preparations for diverse applications. The implications of this study for
routine light scattering characterization of extruded vesicles are discussed.
PMID- 10192933
TI - Mapping the mechanical pulse of single cardiomyocytes with the atomic force
microscope.
AB - The atomic force microscope (AFM) was used to analyse the contractile behaviour
of embryonic chicken cardiomyocytes. The mechanical pulsing of cardiomyocytes was
analysed by observing active single cells as well as cells in a confluent layer.
When embedded in a confluent layer, owing to synchronisation, pulsing of the
cells was often found to be very stable in terms of frequency and amplitude of
the beat, including negative as well as positive amplitudes. Nevertheless, owing
to movements of contraction centres within the layer, a flipping of the sign of
the amplitude did sometimes also occur on a time scale of minutes. In contrast,
single cells often changed between active periods of pulsing and periods of
complete quietness. Also characteristic parameters like beat period and pulse
amplitude were observed to be unstable. Finally, we combined the abilities of the
AFM to image adherent single cells and to record locally beat amplitudes, to
characterise the pulsing behaviour of single cells laterally resolved.
PMID- 10192935
TI - Properties of normal and mutant polypeptide fragments from the dimer self
association sites of human red cell spectrin.
AB - We have examined the properties and interactions of expressed polypeptide
fragments from the N-terminus of the alpha-chain and the C-terminus of the beta
chain of human erythroid spectrin. Each polypeptide comprises one complete
structural repeating unit, together with the incomplete repeat that interacts
with its partner when spectrin tetramers are formed. The shared repeat thus
generated is made up of two helices from the C-terminal part of the beta-chain
and one helix from the N-terminus of the alpha-chain. Three mutant beta-chain
fragments with amino acid substitutions in the incomplete terminal repeat were
also studied. The alpha- and beta-chain fragments were both substantially
monomeric, as shown by sedimentation equilibrium. Circular dichroism analysis and
thermal denaturation profiles revealed that the complete repeat present in each
fragment had entered the stable tertiary fold. Unexpectedly, the conformational
stability of the folded beta-chain repeat was found to be grossly perturbed by
the mutations, all of them well beyond its C-terminal boundary; possible
explanations for this phenomenon are considered. Sedimentation equilibrium showed
that in equimolar mixtures the wildtype alpha- and beta-chain peptides formed a
1:1 complex. Mixing curves, observed by circular dichroism, revealed that
association was accompanied by an increase in alpha-helicity. From continuous
variation profiles an association constant in the range 1-2 x 10(6) M-1 was
inferred. The association was unaffected by the apparently unstructured anionic
tail of 54 residues, found at the C-terminus of the spectrin beta-chain. Of the
three mutations in the beta-chain fragment, one (an Ala-->Val replacement in the
A helix segment of the incomplete repeat) had a relatively small effect on the
association with the alpha-chain fragment, whereas Trp-->Arg mutations in the A
and in the remote B helix segments were much more deleterious. These observations
are consistent with the relative severities of the haemolytic conditions
associated with the mutations.
PMID- 10192936
TI - Changes in the mechanical properties of fibroblasts during spreading: a
micromanipulation study.
AB - Cell morphology is controlled in part by physical forces. If the main mechanical
properties of cells have been identified and quantitated, the question remains of
how the cell structure specifically contributes to these properties. In this
context, we addressed the issue of whether cell rheology was altered during cell
spreading, taken as a fundamental morphological change. On the experimental side,
we used a novel dual micromanipulation system. Individual chick fibroblasts were
allowed to spread for varying amounts of time on glass microplates, then their
free extremity was aspirated into a micropipet at given pressure levels. Control
experiments were also done on suspended cells. On the theoretical side, the cell
was modeled as a fluid drop of viscosity mu, bounded by a contractile cortex
whose tension above a resting value was taken to be linearly dependent on surface
area expansion. The pipet negative pressure was first adjusted to an equilibrium
value, corresponding to formation of a static hemispherical cap into the pipet.
This allowed computation, through Laplace's law, of the resting tension (tau 0),
on the order of 3 x 10(-4) N/m. No difference in tau 0 was found between the
different groups of cells studied (suspended, adherent for 5 min, spread for 0.5
h, and spread for 3 h). However, tau 0 was significantly decreased upon treatment
of fibroblasts with inhibitors of actin polymerization or myosin function. Then,
the pressure was set at 30 mmH2O above the equilibrium pressure. All cells showed
a biphasic behavior: (1) a rapid initial entrance corresponding to an increase in
surface area, which was used to extract an area expansion elastic modulus (K), in
the range of 10(-2) N/m; this coefficient was found to increase up to 40% with
cell spreading; (2) a more progressive penetration into the pipet, linear with
time; this phase, attributed to viscous behavior of the cytoplasm, was used to
compute the apparent viscosity (mu, in the range of 2-5 x 10(4) Pa s) which was
found to increase by as much as twofold with cell spreading. In some experiments
the basal force at the cell-microplate interface was quantitated with flexible
microplates and found to be around 1 nN, in agreement with values calculated from
the model. Taken together, our results indicate a stiffening of fibroblasts upon
spreading, possibly correlated with structural organization of the cytoskeleton
during this process. This study may help understand better the morphology of
fibroblasts and their mechanical role in connective tissue integrity.
PMID- 10192937
TI - Extracellular recording with transistors and the distribution of ionic
conductances in a cell membrane.
AB - Intracellular voltage transients of cultured cells are recorded by transistors
and other planar electrodes as local extracellular voltages. The theoretical
relationship between extra- and intracellular voltage is investigated with a two
compartment circuit using the approximation of a fast, weak and small cell
silicon junction. It is shown that extracellular recording relies on the
difference of specific ionic conductances in the attached and free regions of the
cell membrane. The result rationalizes various observations with neuron
transistors. It guides the optimization of extracellular recording and the
development of cell-based chemical sensors.
PMID- 10192938
TI - Magnetic properties of human liver and brain ferritin.
AB - Human brain (globus pallidus) and liver tissues were investigated by means of
electron microscopy (EM), Mossbauer spectroscopy (MS) and SQUID magnetometry
techniques. Based on MS measurements, the iron present was identified to be in
the ferritin-like form (61-88%) and in the form of a low-spin iron species (the
balance). Its overall concentration was estimated as 1.5(3) mg in the brain and
2.4(5) mg in the liver, per gram of lyophilized tissue. The average core diameter
was determined by EM measurements to be equal to 7.5(1.3) nm for the liver and
3.3(5) nm for the brain. Magnetization measurements carried out between 5 and 300
K yielded an estimation of an average blocking temperature, (TB), as equal to 6.7
K and 8.5 K for the liver and the brain, respectively. From the dependence of
(TB) on the external magnetic field it was concluded that the ferritin-like cores
in the studied samples can be regarded as non-interacting particles. Finally, the
uniaxial magnetic anisotropy constant was determined to be 6 x 10(3) J/m3 for the
liver and 4 x 10(4) J/m3 for the brain.
PMID- 10192939
TI - Three-dimensional quantitative structure-activity relationship (QSAR) and
receptor mapping of cytochrome P-450(14 alpha DM) inhibiting azole antifungal
agents.
AB - Molecular modeling was performed by a combined use of conformational analysis and
3D-QSAR methods to distinguish structural attributes common to a series of azole
antifungal agents. Apex-3D program was used to recognize the common biophoric
structural patterns of 13 diverse sets of azole antifungal compounds
demonstrating different magnitudes of biological activity. Apex-3D identified
three common biophoric features significant for activity: N1 atom of azole ring,
the aromatic ring centroid 1, and aromatic ring centroid 2. A common biophore
model proposed from the Apex-3D analysis can be useful for the design of novel
cytochrome P-450(14 alpha DM) inhibiting antifungal agents.
PMID- 10192940
TI - Holographic electron density shape theorem and its role in drug design and
toxicological risk assessment.
AB - Each complete, boundaryless molecular electron density is fully determined by any
nonzero volume piece of the electron density cloud. This inherent feature of
molecules, called the "holographic" property of molecular electron densities,
provides a strong foundation for the local, quantum chemical shape analysis of
various functional groups, pharmacophores, and other local molecular moieties. A
proof is presented for the relevant molecular shape theorem, the "holographic
electron density shape theorem", and the role of this theorem in quantum
chemical, quantitative shape-activity relations (QShAR) is discussed. The quantum
chemical methods of molecular shape analysis can be extended to ab initio quality
electron densities of macromolecules, such as proteins, as well as to local
molecular moieties, such as functional groups or pharmacophores, based on the
transferability and additivity of local, fuzzy density fragments and the
associated local density matrixes within the framework of the ADMA (Adjustable
Density Matrix Assembler) approach. In addition to new results on chemical
bonding and the development of macromolecular force methods, the new
methodologies are also applicable to QShAR studies in computer-aided drug
discovery and in toxicological risk assessment.
PMID- 10192941
TI - Indexing scheme and similarity measures for macromolecular sequences.
AB - Nucleotide composition and distribution along a DNA sequence is known to play a
vital role in the determination of gene functions. Protein coding regions,
regulatory sequences, and other functional regions are determined generally by
homology studies with comparable genes from other species or specific
experimental verification. With the rapid and explosive increase in sequence
information, new computational techniques for rapid determination of such
information and comparative studies of different genes are becoming necessary
which ideally should encompass not only DNA sequences but other macromolecular
sequences as well.
PMID- 10192942
TI - Topological shape and size of peptides: identification of potential allele
specific helper T cell antigenic sites.
AB - A database of primary sequences of 28 immunogenic peptides, known to elicit T
cell response, derived from five different haplotypes was compiled to identify
allele specific helper T cell antigenic sites using a rule based graph
theoretical method. The prediction was based on the identification of allele
specific patterns in the form of "topological shape and size" present in the
peptides. Indices computed from weighted connected graph models of amino acid
side chains and peptides were used in this purpose. The system was trained by 10
Ad and 10 non-Ad restricted peptide sequences, assigned actives and inactives,
respectively, chosen randomly from the database, and four Ad and four non-Ad
restricted sequences were kept as test peptides. This allowed the system to learn
about "topological shape and size" specific for Ad restricted peptides from the
differences, if any, they had with the inactive peptides in that respect. The
system made 100% correct prediction for the training set peptides and
misclassified only one inactive peptide of the test set. The system also
identified crucial residues for lambda repressor 12-24 and insulin A-chains. This
identification also shows that activity related/crucial residues could be located
at varying distances from the peptide terminals. To our knowledge, the method is
unique of its kind in the literature and may find application in the rational
design of synthetic vaccines and other peptides of immunological importance.
PMID- 10192943
TI - Superpendentic index: a novel topological descriptor for predicting biological
activity.
AB - A simple highly degenerating, pendenticity based, topological descriptor termed
as superpendentic index has been conceptualized and its discriminating power
investigated with regard to antiulcer activity. A data set consisting of 128
analogues of 4-substituted-2-guanidino thiazoles was selected for the present
study. These analogues are reversible, competitive, and selective inhibitors of
gastric H+,K(+)-ATPase enzyme. The value of superpendentic index of each analogue
in the data set was computed and active range was identified. The biological
activity assigned to each analogue using superpendentic index was subsequently
compared with the reported in vitro and in vivo inhibitory activities. The
accuracy of classification of analogues based on in vivo activity was found to be
82% in the active range using superpendentic index.
PMID- 10192945
TI - Response-surface analyses for toxicity to Tetrahymena pyriformis: reactive
carbonyl-containing aliphatic chemicals.
AB - A response-plane has been developed with Tetrahymena pyriformis population growth
impairment toxicity data [log 1/50% growth inhibitory concentration (IGC50)], the
1-octanol/water partition coefficient (log Kow), and the energy of the lowest
unoccupied molecular orbital (Elumo). A statistically robust plane [log 1/IGC50 =
0.530 (log Kow) -0.890 (Elumo) -0.271, n = 50, s = 0.295, r2 = 0.855, F = 145]
was found for reactive carbonyl-containing aliphatic chemicals. These compounds
had a variety of electrophilic mechanisms of action and included aldehydes acting
as Schiff-base formers, alpha,beta-unsaturated aldehydes and alpha,beta
unsaturated ketones acting as Michael-type acceptors, and selected alpha-diones
acting as selective binders to arganine residues; gamma-diones acting as
selective binders to tubulin; and beta-diones with unknown mechanisms of action.
Outliers to this model broadly fell into two groups: small reactive molecules
(e.g., acrolein) that were more toxic than predicted and molecules in which the
reactive center was sterically hindered by an alkyl group (e.g., 2,4-dimethyl-2,6
heptadienal) that were less toxic than predicted.
PMID- 10192944
TI - Validation and subsequent development of the DEREK skin sensitization rulebase by
analysis of the BgVV list of contact allergens.
AB - The DEREK knowledge-based computer system contains a subset of approximately 50
rules describing chemical substructures (toxophores) responsible for skin
sensitization. This rulebase, based originally on Unilever historical in-house
guinea pig maximization test data, has been subject to extensive validation and
is undergoing refinement as the next stage of its development. As part of an
ongoing program of validation and testing, the predictive ability of the
sensitization rule set has been assessed by processing the structures of the 84
chemical substances in the list of contact allergens issued by the BgVV (German
Federal Institute for Health Protection of Consumers). This list of chemicals is
important because the biological data for each of the chemicals have been
carefully scrutinized and peer reviewed, a key consideration in an area of
toxicology in which much unreliable and potentially misleading data have been
published. The existing DEREK rulebase for skin sensitization identified
toxophores for skin sensitization in the structures of 71 out of the 84 chemicals
(85%). The exercise highlighted areas of chemistry where further development of
the rulebase was required, either by extension of the scope of existing rules or
by generation of new rules where a sound mechanistic rationale for the biological
activity could be established. Chemicals likely to be acting as photoallergens
were identified, and new rules for photoallergenicity have subsequently been
written. At the end of the exercise, the refined rulebase was able to identify
toxophores for skin sensitization for 82 of the 84 chemicals in the BgVV list.
PMID- 10192946
TI - Three-dimensional quantitative structure-activity relationships from tuned
molecular quantum similarity measures: prediction of the corticosteroid-binding
globulin binding affinity for a steroid family.
AB - Predictive models based on tuned molecular quantum similarity measures and their
application to obtain quantitative structure-activity relationships (QSAR) are
described. In the present paper, the corticosteroid-binding globulin binding
affinity of a 31 steroid family is studied by means of a multilinear regression
using molecular descriptors derived from mixed steric-electrostatic quantum
similarity matrixes as parameters, obtaining satisfactory predictions. A
systematic procedure to treat outliers by using triple-density quantum similarity
measures is also presented. This method depicts an alternative to the grid-based
QSAR techniques, providing a consistent approach that avoids problematic result
dependency on the grid parameters.
PMID- 10192947
TI - Modeling antileukemic activity of carboquinones with electrotopological state and
chi indices.
AB - The antileukemic activity (medium effective dose, MED) of a set of 37
carboquinones was modeled using a combination of the electrotopological state (E
state) and molecular connectivity indices with multiple linear regression. A four
variable model gave good statistics: r2 = 0.90, s = 0.21. Using the leave-one-out
method, the cross-validation statistics indicate a model useful for prediction:
r2press = 0.85, spress = 0.26. The same variables were used to model the optimum
effective dose (OD): r2 = 0.88, s = 0.19. The cross-validation statistics
indicate a model useful for prediction: r2press = 0.83, spress = 0.23. The
descriptor variables are interpreted in terms of the molecular structure.
PMID- 10192948
TI - Definition of a pharmacophore for partial agonists of serotonin 5-HT3 receptors.
AB - A definition of a partial agonists serotonin 5-HT3 pharmacophore was carried out
by considering a three-dimensional model which correlates the chemical structures
of series of piperazinopyrrolothienopyrazines, piperazinopyridopyrrolopyrazines,
piperazinopyrroloquinolaxines, piperazinopyridopyrroloquinoxalines,
aminoalkyloximinopyrroloindoles, aminoalkyloximinothienopyrrolizines, and
aminoalkyloximinopyrrolizines with the biological affinities. The model is formed
by five features corresponding to two hydrogen bond acceptors, one aromatic ring,
one hydrophobic group, and one positive ionizable site (quaternary ammonium
ions). The nature of the features and the distances between them explain the
partial agonist activities of these compounds.
PMID- 10192949
TI - A computational study of intramolecular proton transfer in gaseous protonated
glycine.
AB - The minimum energy paths for intramolecular proton transfer between the amino
nitrogen and carbonyl oxygen atoms in gaseous protonated glycine were estimated
at the Hartree-Fock (HF) and second-order Moller-Plesset Perturbation (MP2)
levels of theory. Potential energy profiles and their associated reactant,
transition state, and product species calculated at the MP2/6-31G* level were
shown to differ significantly from those obtained at the HF/6-31G* level. Effects
of electron correlation and basis functions on the calculated geometries and
energies of relevant species were examined at the HF, MP2, MP4, CCSD, and B3LYP
levels using the 6-31G*, 6-31G**, 6-31+G**, 6-311+G**, 6-31+G(2d,2p), 6
311+G(3df,2p), cc-pVDZ, aug-cc-pVDZ, and cc-pVTZ basis sets. The HF and MP2
optimized levels with the 6-31G*, 6-31G**, 6-31+G**, and 6-311+G** bases were
used to calculate the thermodynamic and kinetic properties of the proton transfer
reaction at 298.15 K and 1 atm, which include enthalpy, entropy, Gibbs free
energy, equilibrium constant, potential energy barriers, tunneling transmission
coefficients, and rate constants. Results indicate that the proton in a carbonyl
O-protonated glycine undergoes a rapid migration to the amino nitrogen atom,
while the reverse process is extremely unfavorable. The objective of this work is
to develop practical theoretical procedures for studying proton transfer
reactions in amino acids and peptides and to assemble physical data from these
model calculations for future references.
PMID- 10192951
TI - Modeling of the interaction between new ethidium derivatives and TAR RNA of HIV
1.
AB - During the HIV-1 replication process, interactions between the first sequence of
RNA synthesized named TAR RNA and a viral protein named Tat permit a fast and
efficient transcription of viral DNA in RNA. Based on the NMR structure of TAR
RNA found on the PDB, new derivatives of ethidium were designed by molecular
modeling to inhibit this interaction. The studied molecules are composed of three
domains: an arginine, a linker, and an ethidium. Three linkers of different
lengths were considered in the first step, with the TAR RNA-arginine interaction
and the intercalation of the ethidium simulated by docking methods. In a second
step, the structure of the TAR RNA was completed to obtain a whole ethidium
interaction site and docking of the whole studied molecules was investigated.
Molecules were synthesized and tested on infected cells. The predicted models and
activity are in good agreement with the reported experimental results.
PMID- 10192950
TI - Prediction of the brain-blood distribution of a large set of drugs from
structurally derived descriptors using partial least-squares (PLS) modeling.
AB - In this study, the multivariate partial least-squares projections to latent
structures (PLS) technique was used for modeling the brain-blood concentration
ratio (BB) of 61 structurally diverse compounds. The PLS model was based on
molecular descriptors that can be calculated for any compound simply from a
knowledge of its molecular structure, and the model included several topological
and constitutional descriptors. The PLS analysis resulted in a significant three
component model with the following statistics: r = 0.922, Q = 0.867, s = 0.318, n
= 58, and F = 102. The predictive ability of the model was assessed by means of
crossvalidation and also by using BB partitioning data, BBB permeability data,
and 1 set of qualitative brain penetration data, resulting in BB distribution
data for 97 compounds. The results indicate that the PLS model developed is
statistically sound and is sufficiently robust for predictive use. Taking into
account the great ease of computation and interpretation of the derived model, it
may be of general utility in predicting BB ratios for a very wide range of new
drugs.
PMID- 10192952
TI - Bicuculline application affects discharge pattern and pulse-duration tuning
characteristics of bat inferior collicular neurons.
AB - This study examines the contribution of GABAergic inhibition to the discharge
pattern and pulse duration tuning characteristics of 101 bat inferior collicular
neurons by means of bicuculline application to their recording sites. When
stimulated with single pulses 56 (55%) neurons discharged 1 or 2 impulses (phasic
responders), 42 (42%) discharged 3-10 impulses (phasic bursters) and 3 (3%)
discharged impulses throughout the stimulus duration (tonic responders).
Bicuculline application increased the number of impulses and changed the
discharge patterns of 66 neurons. Using 50% difference between maximal and
minimal responses as a criterion, the duration tuning characteristics of these
neurons can be described as band-pass (20, 20%), long-pass (17, 17%), short-pass
(33, 32%), and all-pass (31, 31%). Each band-pass neuron discharged maximally to
a specific duration (the best duration) which was at least 50% larger than the
neuron's responses to a long-duration pulse and a short-duration pulse. In
contrast, each long- or short-pass neuron discharged maximally to a range of long
or short duration pulses. Bicuculline application changed the duration tuning
characteristics of 65 neurons. Possible mechanisms underlying duration tuning
characteristics and the behavioral relevance to bat echolocation are discussed.
PMID- 10192953
TI - Decrease in occurrence of fast startle responses after selective Mauthner cell
ablation in goldfish (Carassius auratus).
AB - A single action potential in one of a pair of reticulospinal neurons, the
Mauthner cells, precedes a short-latency electromyographic response of the trunk
and tail musculature on the opposite side of the body and a fast startle response
in goldfish. It has been postulated that not only the Mauthner cell, but also an
array of neurons can trigger or participate in fast startle responses (Eaton et
al. 1991). We have selectively ablated the Mauthner cells in goldfish to study
how neurons of the brainstem fast startle response network interact. The
probability of eliciting a fast startle response was significantly less in fish
with double Mauthner cell ablations, as compared to the responsiveness of control
fish. The finding that there is a significant decrease in the occurrence of fast
startle responses in animals with no Mauthner cells, implies that the Mauthner
cell may play a role in triggering the involvement of the other network elements
in fast startle responses. We hypothesize that Mauthner cell activation may be
important in bringing those reticulospinal neurons that are "primed" by the
behavioral context to threshold and provides the basis for studies focused on the
interactive nature of the brainstem startle response network.
PMID- 10192954
TI - Coding of amplitude modulation in the auditory midbrain of the bullfrog (Rana
catesbeiana) across metamorphosis.
AB - The functional development of the auditory system across metamorphosis was
examined by recording neural activity from the torus semicircularis of larval and
postmetamorphic bullfrog froglets in response to amplitude-modulated sound.
Multiunit activity in the torus semicircularis during early larval stages showed
significant phase-locking to the envelopes of amplitude-modulated noise bursts,
up to modulation rates as high as 250 Hz. Beginning at metamorphic climax and
continuing into the froglet period, phase locking was restricted to the more
limited frequency range characteristic of adult frogs. The onset of operation of
the tympanic pathway does not reinstate the highly synchronous neural activity
characteristic of the operation of the fenestral pathway. Modulation transfer
functions based on spike count did not show tuning for modulation rate in early
stage tadpoles, but a greater variety of shapes of these functions emerged as
development proceeded. Most of the different kinds of modulation transfer
functions seen in adult frogs were also observed in froglets, but band-pass
functions were not as sharply peaked. These data suggest that different neural
codes for processing of the periodicity of complex signals operate in early stage
tadpoles than in postmetamorphic froglets.
PMID- 10192955
TI - Differential channeling of sensory stimuli onto a motor neuron in the leech.
AB - We studied a specific sensory-motor pathway in the isolated leech ganglia.
Pressure-sensitive mechanosensory neurons were stimulated with trains of action
potentials at 5-20 Hz while recording the responses of the annulus erector
motorneurons that control annuli erection. The response of the annulus erector
neurons was a succession of excitatory postsynaptic potentials followed by
inhibitory postsynaptic potentials. The excitatory postsynaptic potentials had a
brief time-course while the inhibitory postsynaptic potentials had a prolonged
time-course that enabled their temporal summation. Thus, the net effect of
pressure-sensitive neuron stimulation on the annulus erector neurons was
inhibitory. Both phases of the response were mediated by chemical transmission;
the excitatory postsynaptic potentials were transmitted via a monosynaptic
pathway, and the inhibitory postsynaptic potentials via a polysynaptic one. The
pattern of expression of this dual response depended on the field of innervation
of the sensory neuron and it was under the influence of cell 151, a non-spiking
interneuron, that could regulate the expression of the hyperpolarization. The
interaction between pressure-sensitive neurons and annulus erector neuron reveals
how sensory specificity, connectivity pattern and regulatory elements interplay
in a specific sensory-motor network.
PMID- 10192956
TI - Occurrence of pesticides and polychlorinated biphenyls in water of the Nile river
at the estuaries of Rosetta and Damiatta branches, north of Delta, Egypt.
AB - A study was conducted from summer 1995 to summer 1997 to assess the seasonal
occurrence of pesticide residues and other organic contaminants, polychlorinated
biphenyls (PCBs), in water at the estuaries of Rosetta and Damiatta branches of
the Nile river. The results indicated that organochlorine compounds (OCs)
including HCB, lindane, p,p'-DDE, p,p'DDD, p,p'-DDT, aroclor 1254 and aroclor
1260 were present in all the water samples at concentration levels ranging
between 0.195-0.240, 0.286-0.352, 0.035-0.067, 0.019-0.033, 0.024-0.031, 0.390
0.70 and 0.166-0.330 microgram/l, respectively. The levels of these compounds
were higher in water of Damiatta branch than those found in water of Rosetta
branch. Aldrin, dieldrin and endrin were not detected in all water samples. Only
4 compounds from 36 organophosphorus insecticides, fungicides and s-triazine
herbicides tested were detected in water samples collected during summer and
autumn seasons from Rosetta branch. The concentration levels of these detected
compounds, dimethoate, malathion, captan, and ametryne, ranged from 0.011 to
0.340 microgram/l, respectively. Similar compounds during the same seasons as
found in water of Rosetta branch were also detected in water of Damiatta branch
except ametryne. The levels of the detected compounds (dimethoate, malathion and
captan) ranged between 0.030 and 0.330 microgram/l. The levels of detected
organophosphorus insecticides, fungicides and s-triazine herbicides were in the
order: dimethoate > malathion > captan > ametryne.
PMID- 10192958
TI - Surround articulation. I. Brightness judgments.
AB - It has been hypothesized that brightness judgments require an estimate of the
illuminant. Making this estimate is difficult since luminance edges can be the
result of changes in either illumination or reflectance. Articulation is the
addition of equally spaced incremental and decremental patches within a surround
while preserving the surround's space-average luminance. It is proposed that
articulation enhances the inference that the surround's luminance edge is due to
a change in illumination rather than in reflectance. Articulation results in a
corresponding shift in brightness judgments for test-patch increments but not for
decrements. This finding concurs with Arend and Goldstein's [J. Opt. Soc. Am. A
4, 2281 (1987)] reported shifts in brightness as simple center-surround stimuli
are transformed into more complex ecologically valid Mondrians.
PMID- 10192957
TI - Chlorinated pesticide residues in surface sediments from the River Kaveri, south
India.
AB - Chlorinated compounds have preferential attraction for organic phases found in
sediments. Usage of chlorinated pesticides in agriculture and vector control is
more in developing countries. The residue levels of HCH isomers, and DDT, and its
metabolites were quantified in surface sediments from the River kaveri and
Coleroon in Tamil Nadu state, South India. The concentration of HCH ranged from
4.35 to 158.4 ng g-1 (dry wt.). Among the isomers of HCH, alpha-HCH is
predominant followed by beta and gamma-HCH. The levels of DDT varied from 0.69 to
4.85 ng g-1 (dry wt.). Among the DDT compounds, p,p'-DDE quantified more (> 40%)
in all the sites. This suggests that p,p'-DDE is a major breakdown
(dehydrochlorination) product of DDT in the sediment compartment. Higher
concentration of HCH residues reveals its large usage in agriculture. The flux of
pesticide residues from land to river including downward flux to sediment is
less.
PMID- 10192959
TI - Surround articulation. II. Lightness judgments.
AB - It has been hypothesized that to achieve color constancy, lightness judgments
require an estimate of the illuminant. A companion paper [J. Opt. Soc. Am. A 16,
793 (1999)] suggests that surround articulation enhances the likelihood that a
global luminance edge will be interpreted as being due to changes in illumination
rather than in reflectance. Articulation is the process of adding equally spaced
incremental and decremental patches within a surround while preserving the
surround's space-average luminance. Such a process results in lightness judgments
that correlate perfectly with equal local ratio matches. For decrements,
lightness constancy does not require articulation. These findings help explain
why Arend and Goldstein [J. Opt. Soc. Am. A 4, 2281 (1987)] obtained color
constancy with complex Mondrian surrounds but not with simple center surrounds.
PMID- 10192960
TI - Apodization by the Stiles-Crawford effect moderates the visual impact of retinal
image defocus.
AB - Previous optical modeling of the human eye with large pupils has predicted a
larger impact of defocus on the human contrast sensitivity function and
modulation transfer function than is observed experimentally. Theory predicts
that aberrations and the Stiles-Crawford effect (SCE) should both lead to
increased depth of focus, resulting in higher contrast sensitivities and
veridical (not phase-reversed) perception over a larger range of spatial
frequencies in defocused retinal images. Using a wave optics model, we examine
these predictions quantitatively and compare them with psychophysical experiments
that measure the effect of defocus on contrast sensitivity and perceived phase
reversals. We find that SCE apodization has its biggest effect on defocused image
quality when defocus and spherical aberration have the same sign. A model
including typical amounts of spherical aberration and pupil apodization provides
a dramatically improved prediction of the effects of defocus on contrast
sensitivity with large pupils. The SCE can significantly improve defocused image
quality and defocused vision, particularly for tasks that require veridical phase
perception.
PMID- 10192961
TI - Spatial coherence of forward-scattered light in a turbid medium.
AB - We study spatially coherent forward-scattered light propagating in a turbid
medium of moderate optical depth (0-9 mean free paths). Coherent detection was
achieved by using a tilted heterodyne geometry, which desensitizes coherent
detection of the attenuated incident light. We show that the degree of spatial
coherence is significantly higher for light scattered only once in comparison
with that for multiply scattered light and that it approaches a small constant
value for large numbers of scattering events.
PMID- 10192962
TI - Elicitin 172 from an isolate of Phytophthora nicotianae pathogenic to tomato.
AB - Elicitin 172, an acid protein with elicitor activity, has been isolated in true
form from culture filtrates of Phytophthora nicotianae, the causal agent of crown
and root rot of tomato (Lycopersicon esculentum). The M(r) (10,349 +/- 1) of the
purified protein, determined by ES-MS, is identical to that calculated for
parasiticein using the mean isotopic composition and assuming the occurrence of
three disulfide bridges. The primary structure of elicitin 172, determined using
also MALDI-MS experiments, shows complete identity with parasiticein, with
elicitin 310 and a cloned elicitin gene from P. parasitica (= P. nicotianae),
confirming conservation of the elicitin sequence within a single species. The
protein induces necrosis (hypersensitive reaction) on tobacco, but no symptoms on
tomato, when applied on the leaves. Tomato pretreated with elicitin 172 was
affected by P. nicotianae, as well as by the phytotoxic aggregates, naturally
occurring with the elicitin in the non permeated dialysis fraction of culture
filtrates. Finally, the elicitin induce protection of capsicum (Capsicum annuum)
and vegetable marrow (Cucurbita pepo) from P. capsici.
PMID- 10192963
TI - Purification and characterization of acetyl coenzyme A: 10-hydroxytaxane O
acetyltransferase from cell suspension cultures of Taxus chinensis.
AB - An O-acetyltransferase that catalyzes the regiospecific acetylation of a range of
taxanes possessing an unsubstituted 10-hydroxyl group was detected and purified
to apparent electrophoretic homogeneity from a cytosolic fraction of Taxus
chinensis cell cultures. The purification involved negative calcium phosphate
adsorption, sephadex desalting, DEAE, AcA44 chromatography, HighQ, CHT II, HiTrap
Blue, Phenylsepharose and Mimetic Green purification steps. The purified
acetyltransferase was found to be a monomeric protein of 71 +/- 1.5 kDa that is
highly regio- and stereospecific towards the 10 beta-hydroxyl group of the taxane
molecule and is also active towards 10-desacetylbaccatine III. The
acetyltransferase reaction had a pH optimum of 9.0 with halfmaximal activities at
pH 6.8 and 10.8, respectively. The temperature optimum was at 35 degrees C and
the isoelectric point at 5.6. The apparent K(m) values for 10
desacetyltaxuyunnanine C and acetyl CoA were 23 and 61 microM, respectively. The
turnover rate for the enzyme using both substrates was 0.2 mol mol-1 of enzyme.
The kinetic optimum was determined to be Kcat/K(m) = 8.7 s-1 L M-1.
PMID- 10192964
TI - Molecular authentication of Panax species.
AB - Using conserved plant sequences as primers, the DNA sequences in the ribosomal
ITS1-5.8S-ITS2 region have been amplified and determined for six Panax species,
P. ginseng C. A. Mey. (Oriental ginseng), P. quinquefolius L. (American ginseng),
P. notoginseng (Burkill) F. H. Chen (Sanchi), P. japonicus C. A. Mey. (Japanese
ginseng), P. trifolius L. and P. major Ting, as well as two common adulterants of
ginseng, Mirabilis jalapa L. and Phytolacca acinosa Roxb. An authentication
procedure based upon the restriction fragment length polymorphism (RFLP) in the
region is able to differentiate between P. ginseng and P. quinquefolius, and to
discriminate the ginsengs from the two common poisonous adulterants. Broader
application of this approach to authenticate other morphologically similar
Chinese medicinal materials is rationalised.
PMID- 10192965
TI - Steroidal saponins from the aerial parts of Dracaena draco and their cytostatic
activity on HL-60 cells.
AB - Chemical examination of the aerial parts of Dracaena draco has led to the
isolation of a total of nine steroidal saponins, including five new ones. The
structures of the new saponins were determined by spectral data and a few
chemical transformations to be (23S,24S)-spirosta-5,25(27)-diene-1 beta,3
beta,23,24-tetrol 1-O-{O-(2,3,4-tri-O-acetyl-alpha-L-rhamnopyranosyl)-(1-->2)
alpha-L -arabinopyranosyl} 24-O-beta-D-fucopyranoside, (23S,24S)-spirosta
5,25(27)-diene-1 beta,3 beta, 23,24-tetrol 1-O-{O-alpha-L-rhamnopyranosyl-(1-->2)
alpha-L -arabinopyranoside}, (23S,24S)-spirosta-5,25(27)-diene-1 beta,3
beta,23,24-tetrol 1-O-{O-(4-O- acetyl-alpha-L-rhamnopyranosyl)-(1-->2)-alpha-L
arabinopyransoide} , (23S)-spirosta-5,25(27)-diene-1 beta,3 beta,23-triol 1-O-{O
alpha-L- rhamnopyranosyl)-(1-->2)-alpha-L-arabinopyranoside} and (23S,24S)
spirosta-5,25(27)-diene-1 beta,3 beta,23-triol 1-O-{O-(4-O-acetyl-alpha-L
rhamnopyranosyl)-(1-->2)-alpha-L- arabinopyranoside}. The isolated saponins were
evaluated for their cytostatic activity on leukemia HL-60 cells.
PMID- 10192966
TI - Two bioactive mono-tetrahydrofuran acetogenins, annoglacins A and B, from Annona
glabra.
AB - Two new bioactive mono-THF Annonaceous acetogenins, annoglacins A and B, have
been isolated from the fractionated ethanolic extracts of the leaves of Annona
glabra, directing the fractionation with the brine shrimp lethality test (BST).
Their structures were elucidated based on spectroscopic and chemical methods and
the absolute stereochemistries were determined by the advanced Mosher ester
method. Annoglacins A and B were selectively 1000 and 10,000 times, respectively,
more potent than adriamycin against the human breast carcinoma (MCF-7) and
pancreatic carcinoma (PACA-2) cell lines in our panel of six human solid tumor
cell lines.
PMID- 10192968
TI - The antimicrobial resistance crisis in hospitals calls for multidisciplinary
mobilization.
PMID- 10192967
TI - Phenolic aporphine-benzylisoquinoline alkaloids from Thalictrum faberi.
AB - From the roots of Thalictrum faberi, six new phenolic aporphine
benzylisoquinoline alkaloids, 3-hydroxy-6'-desmethyl-9-O-methylthalifaboramine
(1), 3-hydroxythalifaboramine (2), 6'-desmethylthalifaboramine (3); 3,5'
dihydroxythalifaboramine (4), 5'-hydroxythalifaboramine (5) and 3-hydroxy-6'
desmethylthalifaboramine (6) were isolated. Their structures were established
through the use of one- and two-dimensional NMR techniques. All of the tested
alkaloids showed potent cytotoxic and antimalarial activities.
PMID- 10192969
TI - How to optimize prescription of antimicrobial drugs.
PMID- 10192971
TI - GDEPIH-GOSPIZ Belgian consensus strategies to control antibiotic-resistant
bacteria in hospitals.
PMID- 10192970
TI - Chronic malleolar swelling: a rare diagnosis.
PMID- 10192972
TI - Valaciclovir-induced hepatitis.
PMID- 10192974
TI - [Is there a link between secondary hemochromatosis and genetics? Apropos of 2
cases].
AB - The authors report the case of two patients with secondary hemochromatosis in
whom a C282Y mutation in the heterozygotic form was observed. They discuss the
potential relationship between secondary hemochromatosis and the presence of the
genetic abnormality.
PMID- 10192975
TI - Ankylosing spondylitis and multiple sclerosis.
AB - Ankylosing Spondylitis can be associated with extra-articular involvement.
Besides internal and ocular complications, neurological manifestations such as
single root lesions, compression of the myelum or the cauda equina syndrome have
also been described. We present a patient with ankylosing spondylitis who
developed a monophasic myelopathy resembling multiple sclerosis. Literature data
show no conclusive evidence for an increased association of ankylosing
spondylitis and multiple sclerosis. However, a monophasic myelopathy may be a
separate neurological manifestation associated with ankylosing spondylitis.
PMID- 10192973
TI - Nebivolol versus enalapril in essential hypertension: a long-term double-blind
comparative trial.
AB - Nebivolol was compared in a dose of 5 mg once daily with enalapril 10 mg once
daily over 7 months in a double-blind randomised trial in essential hypertension.
The two drugs had very similar sustained effects in lowering both systolic and
diastolic pressures; neither had an orthostatic component. Both drugs were well
tolerated. No haematological, biochemical, or urinary abnormalities were seen.
PMID- 10192976
TI - [Cardiovascular morbidity in children with human immunodeficiency virus
infection].
AB - Abnormalities of cardiovascular structure and function have been described among
children with human immunodeficiency virus (HIV). In order to evaluate their
occurrence and clinical predictors, 32 children infected with HIV, aged three
months to 13 years (mean age = 3.11 +/- 3.51 years) were studied. Perinatal
transmission was identified in 90% of the children. Twenty-two patients (pts)
(69%) had symptoms, nine being moderately symptomatic and eight severely
symptomatic. Fourteen pts had immunological disturbances and eight of them were
severely immunosuppressed. Twenty-eight pts (88%) had HIV-1 infection and 6
recent Ebstein-Barr virus coinfection. Nineteen were on zidovudine and 14 on
intravenous immunoglobulin treatment. Nineteen cardiovascular abnormalities were
found in 15 pts (47%): 11 cases of pulmonary hypertension by echocardiographic
criteria (eight of them had interstitial lung infiltrates seen on chest X-ray)
and four cases of left ventricular dysfunction requiring anticongestive therapy.
Other abnormalities were: patent ductus arteriosus, septal hypertrophy, mitral
valve prolapse and pericardial effusion (one case each). Surface ECG displayed
right ventricular hypertrophy in four pts, left ventricular hypertrophy in one
patient and unspecific ST-T wave changes in two pts. Fourteen pts (44%) had sinus
tachycardia with mean heart rate above the 95th percentile on 24-hour Holter
monitoring. CONCLUSIONS: Cardiovascular abnormalities are frequent among children
with HIV-1 infection in late stages; pulmonary hypertension is the most
frequently found cardiovascular anomaly and seems to be related to either chronic
or recurrent respiratory disease; cardiological follow-up is recommended for HIV
infected children.
PMID- 10192977
TI - [The clustering of cardiovascular risk factors in the urban population of Porto].
AB - The aim of the study was to assess the total prevalence of obesity, non-insulin
dependent diabetes mellitus (NIDDM), hypertension, hypertriglyceridemia,
hypercholesterolemia and central fat distribution, in a population-based survey.
Two-hundred and ten individuals from the community were selected by random digit
dialing. Obesity was defined as a body mass index > or = 25 kg/m2, central
distribution of fat if the waist-to-hip ratio > 0.80 in women and 1.0 in men,
diabetes was diagnosed if fasting plasma glucose levels > or = 140 mg/dl and/or
currently under treatment, hypertension was defined as a systolic blood pressure
> or = 140 mm Hg and/or diastolic blood pressure > 90 mm Hg and/or currently
taking antihypertensive medications, hypertriglyceridemia was defined as a
fasting serum triglyceride concentration > or = 200 mg/kg and
hypercholesterolemia as a fasting serum cholesterol level > or = 200 mg/dl and/or
currently taking specific medication. Prevalence rates of obesity, NIDDM,
hypertension, hypertriglyceridemia, hypercholesterolemia and central fat
distribution were 54.3%, 8.0%, 60.0%, 13.9%, 67.0% and 46.7% respectively. The
prevalence of each of these conditions in its isolated form was 2.8% for obesity,
0.0% for diabetes, 3.8% for hypertension, 0.5% for hypertriglyceridaemia, 12.0%
for hypercholesterolemia and 0.1% for the central fat distribution pattern. The
large differences in prevalence between isolated and combined forms in the six
disorders analyzed indicate a great overlap between these cardiovascular risk
factors, and give epidemiologic support to a proposed metabolic syndrome.
PMID- 10192978
TI - [The first assessment of hepatitis E virus seroprevalence in northern Portugal].
AB - Hepatitis E is an enterically transmitted acute viral hepatitis, etiologically
associated with a recently characterized virus, the hepatitis E virus (HEV).
Outbreaks mainly occur in developing countries and as sporadic cases in endemic
regions. The authors present the first serological assessment in northern
Portugal to assess the presence of anti HEV IgG, using the Elisa test, the EIA
and HEV Abbott, in samples from 50 blood donors and 103 chronic liver disease
patients. In 2 blood donors (4%) and in 7 (6.8%) liver patients, the HEV antibody
was detected with optic densities/cut off always below 2.5. Only one patient had
a sojourn in an endemic region; the presence of anti-HEV was not significantly
associated with other hepatotropic viruses. With this test the authors conclude
that 4% of our blood donors are seropositive for anti-HEV antibody and that this
percentage is not significantly higher in chronic liver disease patients (6.8%).
They also think that a new generation of immunological assays, designed for
serological diagnosis of HEV infection, will provide a further understanding of
hepatitis E epidemiology.
PMID- 10192979
TI - [Profile of the resistance to macrolides and imidazoles of Helicobacter pylori in
a sample of the Portuguese population].
AB - We studied the sensitivity of H. pylori to clarithromycin and metronidazole, as
well as the sensitivity and specificity of H. pylori culture, urease test and
histology on a sample of 166 Portuguese patients. We observed a prevalence of
5.8% resistance to clarithromycin and 60% resistance to metronidazole. The
sensitivity and specificity for the diagnostic tests were: culture 98% and 100%,
urease test 98% and 91%, histology 50% and 95%, respectively.
PMID- 10192980
TI - [BCG vaccine. Its efficacy and impact on the results of tuberculin screening in a
high-risk population].
AB - In a housing estate population with a high prevalence of tuberculosis, the
authors conducted tuberculosis screening with the tuberculin test, and an
investigation with three purposes: evaluation of tuberculosis infection (defined
as > 10 mm on tuberculin test), evaluation of BCG effect on tuberculin test, and
evaluation of BCG efficacy. The data was collected by nurses during the screening
and completed with observation of vaccination records in a health center. The
diagnosis of tuberculosis was done by local specialized health services. The
statistical significance was tested with Chi Square and Fisher Tests. Vaccine
efficacy was calculated on the basis of relative risk of contracting tuberculosis
according to vaccination status. The authors tested tuberculin reactivity on 396
persons -53.5% of whole population resident in the neighbourhood. The infection
was more prevalent in the 15-44-years-old group (31.2%), in males (25.9%) and
black population (30.5%). Only the differences between age groups were
statistically significant. After the discussion of probable bias, the authors
conclude that BCG does not convert the tuberculin test significantly when the
cutpoint is of 10 mm, in a high prevalent tuberculosis population. Therefore, the
tuberculin test could be a good diagnostic test for infection, even in vaccinated
groups. Lastly, the vaccine efficacy was not confirmed, probably because of the
small magnitude of sample size.
PMID- 10192981
TI - [A seroconversion study of the measles component of the MMR vaccine in
adolescents of the town of Sabrosa].
AB - The Portuguese national programme of vaccination has instituted a two-dose MMR
vaccine schedule. The second dose of MMR (measles-mumps-rubella combined vaccine)
is given at 11-13 years of age, for both sexes. This study was conducted to
evaluate the duration of immunity of the monovalent measles vaccine, and the
efficacy of a second dose given as MMR. MMR (Triviraten Berna with the strain
Edmonston-Zagreb) was given to the 38 participants. Blood samples were collected
before and after vaccination. Thirty-six participants had been vaccinated with
measles monovalent vaccine during childhood. To measure anti-measles IgG (mIgG),
an enzyme immunoassay was used. Participants were classified as "susceptible" or
"immune", using 200 mIU/ml (milli international units per millilitre) as the
threshold for "immune". Geometric mean concentration (GMC) of mIgG was 1401
mIU/ml in prevaccination sera (n = 38). Thirty-five (92%) of the adolescents were
"immune". Only the two unvaccinated had a positive measles history. GMC in the
sera of the 36 vaccinated participants was 1301 mIU/ml. Neither the time since
measles vaccination nor age at vaccination were correlated with the levels of
mIgG. After receiving MMR, all adolescents became "immune". GMC of mIgG was 2879
mIU/ml in postvaccination sera (n = 38). In 28 (74%) participants, mIgG levels
increased after receiving MMR. Mean concentration increase was 1082 mIU/ml. For
measles, results support the use of a two-dose MMR vaccine schedule in Portugal.
PMID- 10192983
TI - [Congenital malformations of the upper limb. General considerations].
AB - The authors develop same general considerations about history, embryology,
classification and treatment of congenital upper limb anomalies. They review 62
clinical cases of operated patients in Unit Plastic and Reconstructive Surgery of
Santa Maria Hospital and show same cases.
PMID- 10192982
TI - [The initial loss of consciousness in spontaneous subarachnoid hemorrhage. What
does it mean?].
AB - BACKGROUND AND PURPOSE: Poor outcome and rebleeding, after admission to hospital
of patients with spontaneous subarachnoid hemorrhage (SAH) has been found to be
predicted by loss of consciousness at ictus (LOCi). In this study, we assessed
the clinical and neuro-radiological significance of the LOCi in non-traumatic
SAH. PATIENTS AND METHODS: The authors retrospectively studied 102 patients with
SAH admitted to S. Joao Hospital between January 1, 1989 and December 31, 1992,
who were divided into two groups with and without LOCi and compared according to
clinical and imaging features. RESULTS: Loss of consciousness at ictus was
statistically associated with an age over 52 years (odds ratio, 2.9; 95%
confidence interval, 1.1-7.8); a Hunt and Hess Scale score > ou = 3 (4.4; 1.6
12.3); finding of subarachnoid blood on initial cranial CT scan (5.5; 1.4-26.3);
existence of aneurysm (3.4; 1.3-8.9); a Glasgow Outcome Scale score > ou = 3
(4.69; 1.6-14.1). A poor clinical condition on admission (5.2;1.8-14.5) and
existence of aneurysm (4.1; 1.6-10.6) were the only two findings shown to have an
independent power of significant association with loss of consciousness at ictus,
using logistic regression analysis, with LOCi as a dependent variable.
CONCLUSIONS: In this study, LOCi has independent predictive power for a poor
neurologic condition on admission and for the finding of aneurysm on angiogram.
Loss of consciousness at ictus may be explained by the direct impact of the
initial hemorrhage on the brain from a large tear in the aneurysmal wall, causing
a quick rise in intracranial pressure (with LOCi) but a relatively short bleeding
time.
PMID- 10192984
TI - [The concept of dysthymia. Its clinical usefulness and nosological status].
AB - Dysthymia is currently conceived as an independent diagnostic category in the
area of mood disorders, but the concept is controversial, both from a theoretical
and clinical point of view. This article reviews the concept of dysthymia as well
as its history. The clinical usefulness and validity are examined, taking into
special consideration the influential classificatory notions of DSM-IV.
PMID- 10192985
TI - [The diagnostic importance of erythrocyte dysmorphism in the study of hematuria].
AB - The clinical pathologist often faces the request for the research of dysmorphism
in urinary erythrocytes for evaluation of hematuria. Red cells with a different
shape in the urinary sediment is usual but it is difficult to know when its
presence has really diagnostic meaning. The last concepts about dysmorphic
erythrocytes in urine, mainly the acanthocyte, and its importance in the
differential diagnosis of hematuria are presented in this review.
PMID- 10192986
TI - [Tuberculosis and the kidney].
AB - There has been a recrudescence of tuberculosis, an ancient disease with recent
control by public hygiene and drug therapy. Factors leading to the increased
incidence of tuberculosis include the high incidence of tuberculosis among the
AIDS population, and the emergence of drug-resistant strains of tuberculosis. In
renal failure patients, there is impairment of several aspects of lymphocyte and
granulocyte function. The incidence of tuberculosis has been estimated to be as
much as 10-fold higher among renal failure patients than among the general
population. The authors review the history of tuberculosis, the most significant
clinical and pathological aspects, and practical diagnosis and treatment in renal
tuberculosis and in renal failure.
PMID- 10192987
TI - [Urbach-Wiethe disease/lipoidproteinosis].
AB - The authors present a case of Urbach-Wiethe's disease (lipoid proteinosis), a
rare autosomal recessive disorder, in a 49-year-old female patient with
pathognomonic cranial radiological findings demonstrated by radiology and
computed tomography. The rarity of this pathology made radiological diagnosis
difficult.
PMID- 10192988
TI - [Congenital afibrinogenemia].
AB - The authors present a case of congenital afibrinogenemia. A review of the
literature is made, and some aspects of this rare inherited coagulation disorder
are suggested and commented on.
PMID- 10192989
TI - [Hereditary fructose intolerance].
AB - Hereditary fructose intolerance (HFI) is a rare autosomal recessive, metabolic
disorder, that results from a deficiency of aldolase B (fructose-biphosphate
aldolase) in the liver, kidney and intestine. Recent molecular studies have
identified the mutation A149P in most European patients. We describe the first
case of HFI with molecular analysis in a Portuguese child, presenting the same
mutation of the aldolase B gene. The role of molecular studies in the diagnosis
of HFI risk patients and their families is emphasized.
PMID- 10192990
TI - [Peritonitis in the neonatal period].
AB - The authors report a case of 32-week-old newborn, admitted to the Intensive Care
Unit for Newborns. Mechanical ventilation was needed from the first day of life.
The patient was treated with indomethacin on the second day of life due to patent
ductus arteriosus. On the seventh day pneumoperitoneum was diagnosed, emergency
surgery was performed revealing perforation of Meckel's diverticulum. Perinatal
asphyxia and indomethacin administration probably played an important role in
this process.
PMID- 10192991
TI - [The blue rubber bleb nevus syndrome or Bean's syndrome. A rare cause of
digestive hemorrhage].
AB - A 71-year-old male who had previously suffered from chronic alcoholism was
admitted to the Internal Medicine Service of Coimbra Hospital Center in January
1996 due to asthenia, loss of weight, icterus and abdominal pain, clinical
features that had begun six months before admittance to hospital. A physical
examination revealed that, in addition to icterus, the patient presented multiple
hemangiomas of 1 to 5 cm in diameter, located in the oral cavity, neck, breast
and left axilla. These lesions were bluish, elevated and with a rubber-nipple
consistency, and had been developing for about 15 years. Subsequent examination
revealed normocytic normochromic anemia, cholestatic icterus and the existence of
a gastrointestinal hemangioma located in the esophagus. Excisional biopsy of an
element proved that it was cavernous hemangioma. A subsequent angio-scintigraphy
indicated other aspects suggestive of deep hemangiomas located in the legs, face
and cervical region. The authors had the opportunity of examining other members
of the patient's family, who apparently did not exhibit similar lesions. They
concluded that it was a case of blue rubber bleb nevus syndrome (BRBNS), probably
in its sporadic form. Treatment was essentially conservative and the patient is
well.
PMID- 10192992
TI - [The Sezary syndrome].
AB - Sezary syndrome is a form of cutaneous T-cell lymphoma and, like mycosis
fungoides, results from the malignant proliferation of mature post-thymic T-cell
lymphocytes. The main features are the presence of abnormal mononuclear cells
(Sezary cells) in the peripheral blood and exfoliative erythroderma. The authors
present of a 70-year-old woman admitted to our clinic due to the case pruriginous
and exfoliative erythroderma, subcutaneous nodes and lymphadenopathy. The
clinical diagnosis of Sezary syndrome was confirmed through the identification of
Sezary cells in the peripheral blood by cytochemistry and membrane marker studies
and by lymph node histopathology. Genotypic studies excluded the presence of HTLV
I and HTLV-II sequences in DNA samples and confirmed the monoclonal nature and T
cell origin of this lymphoproliferative disease.
PMID- 10192993
TI - [Fatal liver necrosis due to allopurinol].
AB - Allopurinol hypersensitivity syndrome (AHS) is a severe reaction which is
potentially lethal. Exanthematous rash, fever, eosinophilia, and other severe
reactions such as toxic epidermal necrolysis, acute vasculitis, and severe
hepatic and renal dysfunctions are manifestations of this syndrome. The authors
report a case of lethal massive hepatic necrosis due to allopurinol in a patient
with the asymptomatic hyperuricemia. They also describe the risk factors most
frequently associated with the development of AHS and the strategy for its
prevention and consequent reduction of the mortality associated with this
syndrome.
PMID- 10192994
TI - [Tuberculosis in the year 2000].
PMID- 10192995
TI - [The risk-benefit of the treatment of tuberculosis with a high bacilloscopy
sensitivity in a provincial hospital].
AB - BACKGROUND: To know the incidence and type of hepatic toxicity (HTX) of the
tuberculous chemotherapy and to value the risk-benefit of treatment in our
elderly population in a high sensibility context of the bacilloscopy. PATIENTS
AND METHODS: Prospective study of 161 tuberculous patients with standards of 6
months, from January 1989 to December 1994. 75 patients with (INH, FR, PZ and
ETB) and 83 patients with (INH, RF and PZ). It was accomplished clinical,
analytical and microbiological control to all the patients during 24 months.
RESULTS: 28% of the patients had more than 65 years and a 26% HIV infection. The
tuberculosis (TBC) was disseminated in a 41%. A 74% of the patients ha positive
bacilloscopy. The therapeutic fulfillment was correct in a 85% of the cases. A
48% of HTX was observed, with a 9% of serious HTX (associated with alcoholism and
age greater tan 60 years). In 14% of he patients was changed in a way definitive
the therapeutic standard. There was a 17% of therapeutic failure (associated with
disseminated TBC and HIV infection) and a 7% of relapses. The attributive
mortality of TBC was of a 4%. CONCLUSIONS: The transient and moderate increase in
transaminase activity is frequent and it does not require to modify the
chemotherapy. In the greater patients of 65 years the benefit of trying outweigh
the risk, if is accomplished a narrow follow-up with precocious suspension of the
drugs in the event of serious toxicity.
PMID- 10192996
TI - [The characteristics of patients who have died from tuberculosis].
AB - OBJECTIVE: To analyze the characteristics of the patients died from tuberculosis
(TB) in our hospital. METHOD: We retrospectively reviewed the records of the 46
patients died in-hospital from TB between january, 1992 and june, 1997. MEAN AGE:
55 +/- 19 years (19-85). 35 (76%) males and 11 (24%) females. RESULTS:
DIAGNOSIS: pulmonary (63%), disseminated (26%) and extrapulmonary (11%) TB. 87%
of the patients had previous comorbidity (35% were seropositive for HIV). The
only differences between HIV-infected and non-HIV-infected cases were a greater
proportion of normal chest roentgenograms and of toxicity from therapy in
seropositive patients. The disease was diagnosed at death in 17% of cases.
Chemoprophylaxis had not been used in 5 patients, although they fulfilled
criteria for receiving it. Poor compliance with treatment was noted in 6 (13%)
patients. CONCLUSIONS: We have found a high prevalence of comorbidity in these
patients, which might account for the mortality. Delays in diagnosis, misuse of
chemoprophylaxis and poor compliance with therapy might also be implicated in
some cases.
PMID- 10192997
TI - [Familial hypercholesterolemia and plasma Lp(a) levels: 2 cardiovascular risk
factors].
AB - OBJECTIVE: Lipoprotein (a) (Lp(a)) is a modified LDL particle in human plasma.
Elevated Lp(a) plasma concentration has been associated with increase risk of
premature heart disease in most cross-sectional studies. Familial
hypercholesterolemia (FH) is a genetic disorder characterized by an elevation of
LDL cholesterol (LDL-C) caused by molecular defects in the LDL receptor gene. The
aim of our study is to analyze Lp(a) values in a genetic diagnosed FH group
without coronary heart disease (CHD) and explain the considerable variation in
clinical severity of FH patients. METHOD: We have study plasma lipids and
lipoprotein levels in 60 subjects with familial hypercholesterolemia without CHD
and in 74 normolipidemic controls without personal history of CHD and
dyslipidemia of the Valencia area in Spain. RESULTS: We found differences in
total and LDL cholesterol levels and apo B values as expected and also in plasma
Lp(a) levels and log transformed values between FH subjects and normolipidemic
controls (22.3 mg/dl +/- 19.4 vs 12.5 mg/dl +/- 12.6 p = 0.001 and 1.12 +/- 0.53
vs. 0.84 +/- 0.58 p = 0.008). The percentage of FH subjects with a cut point
Lp(a) value > 20 mg/dl is significantly elevated in this group (47% vs 21% p =
0.002). Because of family relationships within the entire study population we
also have compared 23 FH probands with the normolipidemic controls. Again the
same results have been obtained (Lp(a) levels of 23.21 mg/dl +/- 19.2 vs 12.54
mg/dl +/- 12.63 p = 0.019 and log Lp(a) values of 1.19 +/- 0.42 vs 0.84 +/- 0.58
p = 0.01). CONCLUSION: Our results indicate that FH subjects will have a more
cardiovascular risk due to the potentiation of hypercholesterolemia and elevated
Lp(a) values, indicating the addition effects of two different locus implicated
in premature coronary heart disease and could explain the considerable variation
in clinical severity of FH.
PMID- 10192998
TI - [The behavior of atherogenic indices under the effect of growth hormone in
postoperative disease].
AB - OBJECTIVE: It has been studied the effect of the growth hormone (GH) in the
atherogenic indexes, during the postoperative period in 28 patients, operated for
digestive surgery. METHOD: Patients were divided in: I) control group, patients
without treatment, and II) treatment group, patients treated with 8 U.I. of GH
during five days after the intervention. RESULTS: Results show that, while in the
control group the atherogenic values increased to pathologic levels, in the
treatment group, these values stabilized in the physiological limits.
CONCLUSIONS: Thus, these results let conclude to the beneficial antiatherogenic
effect of growth hormone in the postoperative disease.
PMID- 10192999
TI - [Stays occasioned by patients hospitalized in internal medicine services].
AB - BACKGROUND: Study of average stay in Department of Internal Medicine. METHODS:
Prospective descriptive study in which different clinical-epidemiological
variables and their relation with average stay are analysed. RESULTS: Length of
stay: 13.23 +/- 11.04 days. Increase in the average stay related to age,
specially between 65 and 74 years, and among 45 and 55 (p = 0.02). Longer stays
among those admitted from Other Departments and Urgencies (p = 0.04), and those
destined to Hospitals for Chronic Patients (p = 0.0001). CONCLUSIONS: Alternative
formulas to the conventional hospitalization, coordination among different
sanitary levels and others clinical measures would contribute to reduce this
parameter.
PMID- 10193000
TI - [Varicella pneumonia in the previously healthy adult].
AB - Varicella (chickenpox) is a contagious, self-limited, usually benign disease
common in childhood but uncommon in adulthood. Pneumonia is the most frequent
complication of the disease in adults. We retrospectively review 7 cases of
varicella pneumonia in previously healthy adults diagnosed in our hospital
between 1992 and 1996. All of them were treated with intravenous acyclovir with
good therapeutic response save for a patient who developed respiratory
insufficiency and died 8 days after his admission. Smoking was the only risk
factor detected. Clinical features of our patients are described and the need of
an early diagnosis and treatment of varicella pneumonia is emphasized.
PMID- 10193001
TI - [Diabetes insipidus and adipsic hypernatremia in a patient with a
craniopharyngioma].
AB - A fourteen-year male patient presented a retrochiasmatic craniopharyngioma. Aer
transcranial surgical resection, the patient had diabetes insipidus, which
presented an interphase with manifestations of inadequate secretion of ADH. The
patient was adequately treated with intranasal desmopresin, but aer i.v. fluid
replacement was withdrawn, severe dehydration occurred. This was attributed to
loss of the thirst reflex, due to surgical lesion of the lamina terminalis, where
the osmoreceptor neurons are located. This case underscores the complications
with body fluids and osmolality which may occur after surgery of hypothalamic
lesions; i.e. diabetes insipidus (which may have a triphasic course), and
adipsia, an infrequent complication due to absence of thirst.
PMID- 10193002
TI - [Neurocysticercosis in Spain. Apropos 4 cases seen in immigrant patients from
endemic countries].
AB - Neurocysticercosis is a helminthiasis of the central nervous system produced by
the encysted larvae of the pork tapeworm Taenia solium. We report 4 cases of
neurocysticercosis observed in immigrants from endemic areas (India and Latin
America). Three of the patients were diagnosed because of new onset of seizures,
all of the no received anthelmintic therapy with favourable outcome. The fourth
case was a form known as racemose cysticercosis. She was admitted because of CNS
sensorial symptoms with later development of severe intracranial hypertension
that required surgical treatment. All the cases had a positive result in the
ELISA test for cysticercosis. In only one patient chronic epilepsy persisted thus
needing long-term anticonvulsant therapy as a sequelae. Our report helps to
familiarize clinicians with the characteristic radiological findings from
cysticercosis and em s the fact that epidemiological suspicion and serological
data are usually enough to get the diagnosis and avoid unnecessary probes.
PMID- 10193003
TI - [Fixed-dosage combinations in the treatment of hypertension].
AB - The antihypertensive treatment with a single agent is not useful for the arterial
pressure control in a significant number of patients. In such cases, combined
treatment or drug substitution are recommended (sequential or substitutive
monotherapy). In the last years, the fixed dose combinations in one single
pharmaceutical preparation have proliferated. These associations must fulfill a
number of conditions in order to be considered rational, as for instance the
compatibility of its pharmacokinetic features, properly dosing, the absence of
new secondary effects and the high efficiency showed in most of patients. The
advantages of these combinations are the comfort and easiness of the therapeutic
schema, antihypertensive action strengthening, less secondary effects when dose
is reduced, and perhaps a synergism in the protection of target organs. The most
popular combinations are: potassium sparing diuretic plus thiazide, diuretic plus
beta block, diuretic plus ACEI, or calcium antagonist plus ACEI.
PMID- 10193004
TI - [The sleep apnea syndrome as a health problem. An estimation of its prevalence
and morbimortality].
AB - The sleep apnea syndrome (SAS) is a frequent health problem and has severe
consequences. In some reports, their main symptoms like habitual snoring,
excessive daytime sleepiness and nocturnal respiratory pauses can affect up to
65, 22.2 and 27.9% of men, respectively, being less frequent in women. The
incidence of SAS ranges between 4 and 7% of adult general population. Patients
without treatment have an increased mortality (37% to 8 years). Between the
complications that made this adverse outcome are cardiovascular problems
(arterial hypertension, coronary artery disease, sudden death), cerebral
infarctions and other derived from sleepiness like traffic crashes.
PMID- 10193005
TI - [Campylobacter fetus sepsis, pulmonary thromboembolism and an occult neoplasm].
PMID- 10193006
TI - [Coumarin resistance].
PMID- 10193007
TI - [Do you speak Galen?].
PMID- 10193008
TI - [Panarteritis nodosa in adolescents].
PMID- 10193009
TI - [A tuberculous liver abscess in HIV].
PMID- 10193010
TI - [Acquired angioneurotic edema associated with Graves' disease and vitiligo].
PMID- 10193011
TI - [Acute suppurative thyroiditis due to Streptococcus intermedius].
PMID- 10193012
TI - [The empty sella turcica syndrome associated with hypopituitarism].
PMID- 10193013
TI - [Rhabdomyolysis as a complication of carbon monoxide poisoning].
PMID- 10193015
TI - [Rhabdomyolysis, elevated creatine kinase and acute carbon monoxide poisoning].
PMID- 10193016
TI - Minimally invasive treatment of BPH with interstitial diode laser coagulation.
AB - The Authors report their preliminary experience on the use of interstitial laser
coagulation (ILC) for the treatment of benign prostatic hyperplasia (BPH). Twenty
three patients underwent interstitial laser treatment of BPH with the Indigo 830
laser system, from April 1996 to September 1997. Inclusion criteria were: maximum
flow rate < 12 ml/sec, postvoiding residual volume < 300 ml, AUA symptom score >
13. All patients were catheterized for 10 days postreatment. Average follow up
was 10.9 months. Marked improvement was shown at one, three and six months in
terms of AUA score, maximum urinary flow rates, QL index, postvoiding residual
volume, voiding bladder pressure values and prostatic weight reduction. No major
complication were reported. The Authors believe that ILC is an easy and effective
treatment for elder and compromised patients with lower urinary tract symptoms
due to BPH.
PMID- 10193017
TI - [Gonadotropin response to GnRH and seminal parameters in low grade varicocele].
AB - The pathogenetic role of varicocele in male infertility is still controversial.
Although epidemiological data have clearly shown a higher incidence of varicocele
in the population of subfertile and infertile patients, the real effectiveness of
the surgical repair of varicocele, expressed as increase in the pregnancy rate,
is still debated. The presurgical gonadotropin releasing hormone (GnRH) test is
the most reliable predictive index of successful surgical outcome in terms of
fertility. Only patients with an increased gonadotropin response (in particular
FSH) to GnRH will benefit from the surgery. The aim of the present study was to
evaluate the gonadotropin response to GnRH 50 micrograms i.v. in a group of
patients with low-medium grade varicocele. At the beginning of the test, a fine
needle was inserted into the forearm and kept patent by a saline solution. Blood
samples were collected at the following experimental times: 0, +15, +30, +60,
+90, +120 min. The stimulus was administered i.v. as bolus at time 0. The
gonadotropin response to the stimulus and baseline levels of testosterone, PRL,
17 beta oestradiol and SHBG were compared with those of a control group.
Moreover, all the patients underwent semen analysis after 3-7 days' abstinence
and to ultrasound-doppler of the testis. Finally, we preliminarily looked for the
presence of microdeletions on the Yq chromosome by polymerase chain reaction. No
difference in baseline hormonal levels was found between the patients with
varicocele and the controls; the LH response to GnRH was also similar in the two
groups. The patients with varicocele showed a significantly (p = 0.03) higher FSH
response (13.6 +/- 5.9 mUI/ml) to GnRH than controls (3.8 +/- 0.5 mUI/ml). A
significant positive correlation (r = 0.6, p = 0.05) was found between LH peaks
after GnRH testing and varicocele grade. Nine of 11 patients with varicocele
showed significant seminal abnormalities (i.e., oligoasthenospermia): all
patients showed a normal karyotype and no microdeletions were detected on the Yq
chromosome. The authors underline the importance of presurgical GnRH testing in
patients with low grade varicocele, given the close correlation between
gonadotropin-stimulated peaks and varicocele grade found in the study. The
presence of significant seminal abnormalities, even in patients with low grade
varicocele, suggests the use of molecular genetic techniques to detect possible
microdeletions on the Yq chromosome, which may be responsible for the
infertility.
PMID- 10193018
TI - Urinary dosage of nuclear matrix protein 22 (NMP22) like biologic marker of
transitional cell carcinoma (TCC): a study on patients with hematuria.
AB - This study was performed to evaluate the clinical usefulness of nuclear matrix
protein 22 (NMP22) as urinary marker for bladder cancer and to define its role in
comparison with urinary cytology in diagnostic management of patients with
hematuria. MATERIALS AND METHODS: NMP22 values in voided urines were determined
on 90 patients (81 males, 14 females) with macro or microscopical hematuria,
using the NMP22 test-kit (Matritech) based on an enzyme-linked immuno-sorbant
assay. The cut-off value for positive samples was 10U/ml. In all cases urinary
cytology was performed on the same sample. Patients suspected for the presence of
a transitional cell carcinoma (TCC) underwent cytoscopic control. Statistical
signification of the medians difference was analyzed using both medians variance
analysis and Student's test. The increasing in diagnostic predictivity was
analyzed elaborating contingency tables and performing consequently chi 2 test.
RESULTS: 32 cases of TCC were endoscopically detected: sensitivity of
cytopathology was 75.8%, specificity was 62.5%. The positive predictive value of
the cytology was 22% and negative predictive value was 49%. The results
concerning NMP22 dosage are: sensitivity 84%, specificity 62%. Positive
predictive value of NMP22 test was 30% and predictive negative value was 40%. No
significant differences between cytopathology and NMP22 dosage were founded (p >
0.995). Considering both cytopathology and NMP22 dosage, sensitivity was 82.7%
and specificity raises up to 90.6% with statistical signification (P < 0.001).
The median NMP22 value in patients affected by TCC endoscopically confirmed
(group A) was 55.2 U/ml, in subjects with no evidence of malignancy (group B) it
was 19.1 U/ml. The difference shows statistical signification (p < 0.001). In 20
cases with TCC, hystological grading were available and were investigated in
relationship with NMP22 title in U/ml, median NMP22 value for each grade was: CIS
= 102 U/ml, G0 = 35 U/ml, G1 = 30 U/ml, G2 = 66 U/ml, G3 = 54 U/ml. It can be
assessed that NMP22 test is useful in differentiating subjects affected by TCC
from subjects with no evidence of malignancy and may help in early diagnosis of
TCC and in predicting recurrent even if low grade tumors especially if used in
association with cytology and endoscopy.
PMID- 10193019
TI - [Diagnostic approach and therapeutic strategy in 133 infertile patients with
astheno-necrozoospermia].
AB - One-hundred thirty-three patients (aged 22 to 48, median 27 years) found affected
by repetitive severe astheno-necrozoospermia (ASNE) (forward sperm motility <
10%; viable forms < 25%) in their ejaculates detected by both conventional
viability tests (eosin Y exclusion and HOS tests) associated with oligo (51.1%),
poly (3.7%), terato- (82.7%), -zoospermia, hyperdesfoliation of seminal
spermatids (36.8%), hypospermia (11.3%), a comprehensive (history analysis;
physical examination; lab: hormonal, microbiological, hemato-chemical blood
screening, ultrasound scans at didymo-epididymal and prostato-vesicular glands,
genital venous doppler) work-up allowed to recognize the following possible
causes of ASNE: infectious (24.1%), spermiotoxyc (16.5%), hormonal (15.0%),
iatrogenic (12.8%), chronic extratesticular diseases (CETD) (10.9%), varicocele
(6.8%), idiopathic (14.3%). Overall population, except CETD patients gave their
written informed consent about trial options for a three month period: a.
rational, evidence-based treatment, group-standardised for doses and lenght
(treated patients = subgroups T: total number = 71); b. short-term treatment/no
treatment, (matched-control = subgroups Co: total number = 47). Follow-up semen
data performed after completion of the assigned trial, together detected a
conventionally normal percentage (> 25%) of viable sperm (necrozoospermic
responders (NR) in 37 (52.1%) out of subgroup-T patients. All subgroups-T
patient, excepted subgroup-T patient affected by idiophathic ASNE (NR = 0%),
exhibited NR rate (range 50-69.2%) values always significantly higher than
subgroups-Co (NR = 0%, in all subgroups). Moreover, in each subgroup-T patients
the percentages of viable and forward motile sperms values were significantly
higher than matched-controls. The results of this study indicate that in patients
affected by ASNE an andrological comprehensive work-up is mandatory because ASNE
has a heterogeneous pathogenesis and a favourable prognosis, in terms of viable
forms sperm improvement is possible after evidence-based therapeutic strategy.
PMID- 10193020
TI - [Prevention and early diagnosis of testicular neoplasms].
AB - Aetiology of testicular cancer is still poorly characterized, so the prevention
is unlikely to achieve. A fundamental issue is early detection as delay in
presentation is a common feature in patients affected by this disease. Moreover
there is much evidence suggesting a significant association between delay in
diagnosis and clinical stage at presentation particularly for nonseminomas. 176
valuable patients with non seminomatous germ cell tumors of the testis had a
clearly identifiable interval from first symptoms until diagnosis; mean delay was
13.9 weeks, and there was a correlation between difference in delay of I clinical
stage patients (mean: 10.0 weeks) and III stage patients (mean: 18.6 weeks)
ANOVA: p < 0.035. These data suggest that encouraging programmes in order to
provide more informations on testicular cancer and testicular self examination
(TSE) may contribute to reduce the number of young men requiring toxic treatment
and major surgery and even may reduce mortality.
PMID- 10193021
TI - [Fournier's gangrene: report of 2 cases and review of the literature].
AB - Fournier's gangrene is an extensive fulminant infection of the genitals, perineum
or the abdominal wall. Since the first description by Jean Alfred Fournier in
1883 about 700 cases have been reported in the literature. The main aetiological
factors are: perianal, perirectal or periurethral infections, diabetes mellitus
and chronic alcoholism. Many aerobic and anaerobic organisms may be involved.
Mortality rates range from 30-50%. The dramatic course of Fournier's gangrene
requires early recognition, surgical drainage, extensive surgical debridment,
antimicrobial therapy, hyperbaric oxygen therapy, as well as intensive care
treatment in order to prevent irreversible endotoxic shock. We report two cases
of Fournier's gangrene. In both cases symptoms were fever, pain and extensive
cutaneous necrosis in the scroto-perineal region.
PMID- 10193022
TI - Spontaneous partial fibrotic regression of a primary renal carcinoma: a case
report.
AB - Spontaneous regression of non metastatic renal carcinoma is a very unusual
finding in daily urologic practice. Furthermore this is the first case of a
partial primary renal cancer remission documented by hystopathological specimens.
Current hypothesis were discussed.
PMID- 10193023
TI - [Does the neurologic assessment have a decisive role in the early diagnosis of
urinary disorders of uncertain etiology? A case of spinal chordoma].
AB - The Authors report a rare case of detrusor areflexia due to a sacral column
chordoma characterized as initial symptomatology, by dysuria and recurrent
urinary tract infections. The patient was treated for a long time in a
symptomatic way by her physicians. The Authors while discussing the case,
underline the importance of an accurate differential diagnostical framing in
patients with voiding and/or anorectal dysfunctions of uncertain nature. This
framing must exclude those voiding pathologies of neurological origin which are
frequently evinced merely by an aspecific voiding symptomatology of dysuric or
irritative nature.
PMID- 10193024
TI - [Percutaneous drainage of abdominal abscess. A clinical case and issues of
operative ultrasonography in urology].
AB - Percutaneous drainage of intrabdominal abscesses currently is a well established
technique. The use of ultrasound, ever more frequently utilized in urology
department, made urologists autonomous in ultrasound diagnosis and operative
stage. We report on a patient admitted to emergency department in whom acute
prostatitis was diagnosed. Urological consultation was obtained. The ultrasound
examination performed, permitted to reveal the real syntomatology origin and to
make an evaluation about the possible application of ultrasound in diagnosis and
treatment of abdominal abscesses. This was also an occasion to re-examine some
not urological ultrasound cases and their treatment. We believe that, also for
the urologists, morphological knowledge of most frequent abdominal pathologies,
visible by ultrasound, is useful to avoid diagnostic mistakes and useless and
hazardous treatments. In our experience we confirm that percutaneous and non
invasive techniques, if well utilized, have a good cost/benefit ratio. The
percutaneous treatment is also useful to convert an urgent surgical operation
into a well established and programmed one.
PMID- 10193025
TI - [Symptomatic angiomyolipoma of the kidney: report of 2 cases].
AB - Renal angiomyolipoma is an uncommon benign tumor composed of adipose tissue,
dysplastic blood vessels and smooth muscle. The tumor may occur as a distinct
entity or in association with tuberous sclerosis. The diagnosis is usually easy
but a malignant neoplasm can not always be excluded. Tumors smaller than 4 cm are
mostly asymptomatic and usually do not need to be treated. For larger lesions a
treatment is advisable especially in case of symptoms because of the risk of a
severe hemorrhage. The treatment should be as conservative as possible and
nephrectomy preformed only when a malignant tumor can not be excluded or in cases
of life-threatening hemorrhage or widespread infiltration or complete destruction
of the kidney. Today the treatment of choice should be embolisation and on second
line resection of the lesion. Two cases of symptomatic angiomyolipoma are
presented. Both cases are treated by radical nephrectomy.
PMID- 10193026
TI - [Transplantation of islets of Langerhans: quo vadis?].
PMID- 10193028
TI - [Current treatment of closed injuries of the liver: benefits and pitfalls].
AB - STUDY AIM: The management of blunt hepatic trauma has been modified by the
development of conservative methods. Risks and pitfalls of this new approach must
be determined. PATIENTS AND METHODS: From January 1985 to September, 1998, 130
patients with blunt hepatic trauma were treated by the same team. Among them, 38
patients were referred from another centre (21 already having undergone
operations). Eighty patients (61%) had an initial non operative management and 50
patients (39%) underwent emergency laparotomy. Perihepatic packing was performed
in 24 patients, hepatic sutures in 22, limited hepatic resection in six, and
major hepatectomy in two patients only. RESULTS: There were three deaths in the
non operative management group (mortality rate: 3.5%) and 11 patients required a
secondary laparotomy: four for haemorrhage, one for enteric injury, two for acute
pancreatitis, one for bile leakage, one for subphrenic abscess, one for acute
cholecystitis. There were 14 deaths in the emergency laparotomy group (mortality
rate: 28%), including four intraoperative deaths due to haemorrhage and two due
to abdominal compartment syndrome. CONCLUSIONS: In the nonoperative management
group a close clinical survey of the patient is necessary and a secondary
laparotomy often indicated. In the operative management group, early packing
requires reintervention if the patient is unstable. Alternative means of
temporary closure may allow coverage without tension in order to avoid the
abdominal compartment syndrome.
PMID- 10193027
TI - [Monolobar Caroli's disease. Apropos of 12 cases].
AB - BACKGROUND: Caroli's disease is the dilatation of the segmental intrahepatic bile
ducts. It usually affects the entire liver but can occasionally involve only one
lobe, commonly the left. This study included 12 cases of unilobular disease, nine
localised in the left lobe and three in the right lobe, which were all treated by
liver resection. PATIENTS AND METHODS: These 12 patients underwent surgery
between 1974 and 1997. There were six men and six women (mean age: 51 years). The
initial presentation and diagnosis were reported. The mean interval between the
first symptoms and diagnosis was 12.5 years. Eight of the 12 patients had
undergone 22 surgical or endoscopic procedures prior to liver resection. In the
present series a preoperative ultrasonogram or CT scan established the diagnosis
in all cases. Six patients did not have stones in the gallbladder. RESULTS:
Surgical treatment consisted in seven left lobectomies, two left hepatectomies
and three right hepatectomies (Couinaud's classification). A intrahilar
cholangiojejunostomy was performed in five cases. Pathological examination showed
cystic dilatation of the intrahepatic segmental and subsegmental bile ducts,
measuring from a few millimetres to 4 cm, which contained calculi. Two cases were
associated with congenital hepatic fibrosis. An intrahepatic focus of ectopic
pancreatic tissue was seen in one case. There were no cases with
cholangiocarcinoma. One patient developed a biliary fistula which required
reoperation. All patients had an uneventful long term postoperative course except
for one patient who died of colon carcinoma 3 years postoperatively. CONCLUSION:
When associated with other malformations, most notably congenital hepatic
fibrosis, this commonly diffuse disease is called Caroli's syndrome. The unilobar
form, most usually involving the left lobe of the liver, is called Caroli's
disease. Both monolobar and diffuse types are often characterised by recurrent
bouts of cholangitis and, in over half of the cases, by common bile duct stones
without gallbladder stones.
PMID- 10193029
TI - [Percutaneous drainage of infected pancreatic necrosis: an alternative to
surgery].
AB - AIM OF THE STUDY: To describe a technique of percutaneous CT guided catheter
drainage of infected pancreatic necrosis and to report the results of this
technique compared with those of the conventional surgical treatment and of other
percutaneous drainage series. PATIENTS AND METHODS: Between 1992 and 1997, the
series included 32 patients who had a severe acute necrotizing pancreatitis with
a mean Ranson score of 4.6, scored into grade D (n = 10), and grade E (n = 22),
according to the Balthazar radiological staging. Modified Van Sonnenberg 24 F
double lumen catheters were used for continuous irrigation and aspiration.
RESULTS: Forty-nine drains were inserted for 41 infected necroses and eight
abscesses. Among the 32 patients, the proof of infected necrosis was obtained in
26 patients by fine needle aspiration and culture (enterococcus, staphylococcus,
pseudomonas). The average delay of catheter insertion was 23 days after onset of
pancreatitis; the mean duration of drainage was 43 days, and an average of three
catheters per patient was required. Five patients (15%) died, and among the
survivors, 16 (59%) presented 21 complications including 14 enterocutaneous or
pancreatic fistulas. A subsequent surgical procedure including two necrosectomies
was necessary in six patients. CONCLUSION: This study demonstrates that
percutaneous drainage of infected pancreatic necrosis with a 15% mortality and
70% success rate, represents an interesting alternative to conventional surgery.
PMID- 10193030
TI - [Laparoscopic treatment of common bile duct lithiasis. Study of 56 cases].
AB - AIM OF THE STUDY: The aim of this retrospective study was to report the results
of the laparoscopic management of common bile duct stones in an unicentric series
of 56 patients. PATIENTS AND METHOD: From January 1993 to April 1998, 56
patients, 38 women, 18 men (mean age: 59.2 years), underwent a common bile duct
exploration for lithiasis through a laparoscopic approach. The patients were
hospitalised for angiocholitis (n = 13), cholecystitis (n = 11), biliary pain (n
= 29, nine with jaundice), pancreatitis (n = 3), abnormality of hepatic profile
(n = 1). All the patients underwent an intraoperative cholangiography. Removal of
the stones was tried in 50 cases through a choledochotomy, in four through the
cystic duct, using Mirrizi forceps, or Dormia and Fogarty catheters in case of
failure. External biliary drainage and postoperative cholangiography were done
systematically. The average diameter of the common bile duct was 10.5 mm (6-20
mm). RESULTS: In 41 patients, removal of the stones was laparoscopically
successful. In 11 patients, a conversion into laparotomy was necessary for
several reasons. In three patients with common bile duct of small diameter, the
stones were abandoned for a further endoscopic sphincterotomy. There was no
mortality and the morbidity rate was 7%. The mean postoperative hospital stay was
8.6 days (4-20) for all the series and 7.8 days in case of successful
laparoscopic management. CONCLUSION: In 73% of the patients, the treatment of the
common bile duct lithiasis could be achieved laparoscopically, but conventional
approach and endoscopic sphincterotomy are still useful in case of failure of the
laparoscopic management.
PMID- 10193031
TI - [Pelvic filling and perineal reconstruction using longissimus dorsalis
myocutaneous flap after total pelvic exenteration].
AB - AIM: The study aim was to report an original technique for pelvic cavity filling
and perineal floor reconstruction with longissimus dorsalis myocutaneous free
flap after total pelvic exenteration and extensive perineumectomy. PATIENTS AND
METHOD: This technique was used in three patients, two men and one women (mean
age: 53.3 years) after total pelvic exenteration for recurrent carcinoma of the
bladder and/or prostate (n = 1), recurrent rectal carcinoma (n = 1) and extended
vulvar carcinoma (n = 1). In this female patient, who required an extended
perineal resection, it was necessary to use a bilateral flap, but a unilateral
flap is usually sufficient. The vessels of the flap were connected with the
femoral vessels in the Scarpa's triangle by a manual microanastomosis. RESULTS:
The postoperative course was uneventful except for one patient who had an
hemorrhage unrelated to the technique. One patient died after 13 months of septic
complications and the two other patients were alive after 6 and 7 months.
CONCLUSION: The use of longissimus dorsalis myocutaneous free flap is a suitable
procedure in order to fill the pelvic cavity and restore the perineal skin after
a total pelvic exenteration with large perineal resection. Further experience is
necessary to confirm these first attempts.
PMID- 10193032
TI - [Anaplastic cancers of the thyroid. Is healing possible?].
AB - OBJECTIVE: Thyroid anaplastic carcinoma is associated with a very poor prognosis.
The goal of this study was to determine whether an aggressive treatment is
worthwhile. PATIENTS AND METHODS: Of 22 thyroid anaplastic carcinomas confirmed
with immunohistochemistry, 17 were judged eligible for surgery. Total
thyroidectomy was planned in all patients. Frozen section of the lower lateral
lymph nodes was routinely performed and in case of involvement (n = 9), a
modified radical neck dissection was carried out. Fractionated radiotherapy was
started within 5 weeks following surgery: 6,000 cGy was delivered on the thyroid
area and all involved areas while 4,500 cGy was delivered on the lymph nodes of
the neck and of the superior mediastinum when non involved. RESULTS: The three
patients without distant metastasis, with thyroid removal considered as complete,
were still free of disease 10, 12 and 13 years later. One of these patients had
been initially considered inoperable and was operated later when a combination of
radiotherapy and chemotherapy obtained a decrease of the tumor. All other
patients, 13 with incomplete removal and one with pulmonary metastasis died from
their cancer; the median of the survival was 7 months. CONCLUSION: When
anaplastic carcinoma is suspected on clinical appearance, the diagnosis should be
rapidly confirmed with percutaneous biopsy and immunohistochemistry. If a
lymphoma is found, surgery is not indicated. Our results demonstrate that except
for widely infiltrating tumors or distant metastasis, a complete removal of the
tumor should be attempted as soon as possible. Surgery should be followed with
hyperfractionated radiotherapy. Multimodal therapy may result in long-term
survival. A patient free of disease at 5 years may be considered as definitively
cured.
PMID- 10193033
TI - [Interbody arthrodesis using a plasmapore titanium block. Mechanical and
histological experimental study in sheep].
AB - A Plasmapore-coated titanium alloy block was implanted in ewes for the purpose of
providing interbody fusion. Four blocks were implanted in each ewe: one uncoated
block (without Plasmapore) serving as a reference specimen and three blocks
coated with Plasmapore. Mechanical testing and histological study were performed
on five ewes. OBJECTIVES: Determination of the quality of the mechanical and
histological anchorage of the Plasmapore implanted in the interbody space in the
same animal living under conditions of physical strain exerted on the spine.
METHODS: Four months after surgical implantation of the block, the ewes were
sacrificed: the removed spines were frozen for subsequent mechanical analysis and
preserved in a solution of 40 degrees alcohol for subsequent histological
analysis. X-rays were taken to evaluate the positioning of the implant. The
mechanical analysis included extraction tests, measuring the maximum extraction
force and evaluating the stiffness of the system, being indicative of the
mechanical fixation quality. The histological study included both qualitative and
quantitative analysis, together with an evaluation of the osteointegration of the
blocks coated with Plasmapore. RESULTS: After 4 months of implantation, a mean
extraction force of 990 N was necessary for the blocks coated with Plasmapore,
and of 1.338 N for the blocks coated with Plasmapore with additional
osteosynthesis, whereas a mean extraction force of 332 N was necessary for the
uncoated blocks. Anchorage and resistance against uprooting of the blocks coated
with Plasmapore were significantly more efficient. The histological study
revealed the presence of bone neoformation adhering to the implant.
Quantification of this bone formation covering nearly 45% of the implant
perimeter, confirmed both osteointegration of the implant perimeter, confirmed
both osteointegration of the implant surfaces being in contact with the vertebral
endplates and osteoconduction along the lateral surfaces. CONCLUSION: The
titanium Plasmapore block enables interbody fusion due to an osteointegration of
the vertebral endplates by Plasmapore coating, which was proved by the results of
extraction testing and histological study. It should be taken into account that
no additional bone grafts have been used and that the implant had not been forced
into the spongiosa.
PMID- 10193034
TI - [Post mortem diagnostic laparoscopy].
AB - The authors report a case of laparoscopy post mortem for unexplained inpatient
death. It is minimally invasive, easy to perform, accurate, and not disfiguring.
As well, it is easy to accept among mourning families. It should be considered
when consent for conventional autopsy is lacking.
PMID- 10193035
TI - [Hepatic portal venous gas: is it always a sign of severity and surgical
emergency?].
AB - Hepatic portal venous gas is a radiological finding due to the presence of gas in
the portal vein. It was associated with a mortality rate ranging from 75% to 90%
and with an indication for exploratory laparotomy. We report one case following
an abdominal trauma. The portal vein gas was detected on CT Scan. The patient who
was asymptomatic was not operated on and survived. The severity of this
radiological symptom requiring a laparotomy has to be reassessed. CT Scan is the
most efficient method to recognize portal vein gas and its larger use has allowed
to diagnose more cases not detected by simple abdominal X-rays. In conclusion,
surgical exploration should not be done systematically but has to be decided in
relation with the clinical status of the patient.
PMID- 10193036
TI - [Inflammatory pseudotumor of the lung. An anatomoclinical study of a case
report].
AB - One solitary pulmonary nodule was observed in a 47-year-old woman with history of
right thigh liposarcoma 1 year before. Histological examination of the pulmonary
specimen excluded liposarcoma metastasis and revealed an inflammatory
pseudotumor. These unusual lesions with an excellent prognosis may exhibit, as in
our case, atypical radiologic features and nuclear atypia, making the diagnosis
difficult with malignancy.
PMID- 10193037
TI - [Endoscopic surgery of colorectal cancers: is it legitimate?].
PMID- 10193038
TI - [Antoine Joseph Jobert de Lamballe (1799-1867)].
PMID- 10193039
TI - [Application of a new classification of cancers of the cardia].
PMID- 10193040
TI - Propofol: application in veterinary sedation and anesthesia.
AB - Propofol can be used for sedation, induction of anesthesia, and maintenance of
anesthesia in small animal patients. In all these situations recovery from its
effects is typically rapid and smooth. The drug should be administered slowly,
intravenously, to minimize the negative cardiac and respiratory effects seen
after rapid bolus administration. The currently available formulations do not
contain preservatives, and sterile technique should be strictly followed during
its use. Propofol can be used for induction of anesthesia in patients with
preexisting disease with minimal delays in recovery. It does not cause excitement
at low doses so is also useful for sedation of patients undergoing nonpainful
procedures such as radiological examination. This review focuses on the diverse
clinical applications for propofol in a small animal practice including
indications, recommendations, and contraindications as well as a discussion of
the controversies that surround its use.
PMID- 10193041
TI - Pros and cons of using alpha-2 agonists in small animal anesthesia practice.
AB - The alpha-2 agonists have been used in veterinary practice for over 30 years
following the introduction of xylazine (ROMPUN, Bayer Corp., Shawnee Mission, KS)
in 1962. The decision to use alpha-2 agonists in anesthesia practice should be
based on factors including patient disposition, presenting complaint, type of
procedure, and the veterinarian's familiarity with the drug. Controversy
surrounds the issue of using anticholinergic agents concurrent with the alpha-2
agonists. Patient selection and procedure type can aid in determining when use of
an anticholinergic with the alpha-2 agonist is advantageous. Antagonism of alpha
2 agonists can be readily accomplished. Commonly, alpha-2 agonists are used in
combination with other agents to provide neuroleptanalgesia or sedation prior to
general anesthesia.
PMID- 10193042
TI - Sedation and chemical restraint in the dog and cat.
AB - Small animal patients must often undergo veterinary procedures that are painful
or distressful, for which judicious use of sedatives or other agents with
anesthetic or analgesic properties can be useful. If the degree of sedation is
profound enough, such "chemical restraint" may be employed to provide
immobilization for radiographs or minor surgical procedures. The choice of agents
to be used will depend upon the physiologic state and cooperative nature of the
patient and the desired endpoint, ie, anxiolysis versus deep sedation with
analgesia. This report discusses important features of patient assessment,
preparation, equipment needs, consideration of the types of procedures for which
sedation is useful, and recovery considerations. A brief review is included of
the useful effects and contraindications for the various agents employed, and
doses for each are listed. Algorithms are presented for a given category of
patient, leading the practitioner through a decision making strategy to arrive at
examples of sedation or chemical restraint protocols that are commonly found to
be effective by the author.
PMID- 10193043
TI - Balanced anesthetic techniques in dogs and cats.
AB - The term "balanced anesthesia" refers to the use of a mixture of drugs, such that
the advantages of small amounts of drugs are used without having to contend with
the disadvantages of large doses of any one drug. In veterinary practice,
inhalant drugs are usually administered alone to maintain anesthesia, and
balanced anesthetic techniques are rare. Unfortunately, cardiopulmonary function
is reduced in dose-dependent fashion by inhalant drugs and deepening the level of
anesthesia in order to modify autonomic responses to noxious stimuli may increase
morbidity and mortality. This article justifies the use of balanced anesthetic
techniques in veterinary practice and describes the advantages gained by the use
of nitrous oxide, continuous opioid infusion, epidural/spinal opioid
administration, and transdermal opioid administration. These techniques,
described in detail in the article, are easy to learn, relatively inexpensive,
may decrease patient morbidity and mortality, and will provide the veterinarian
with smoother operating conditions.
PMID- 10193044
TI - Anesthesia of the sighthound.
AB - The sighthounds are an ancient group of dog breeds that have been selectively
bred for high-speed pursuit of prey by sight. Probably as a consequence of this
selection process, these dogs have a number of idiosyncrasies that can
potentially adversely affect their anesthetic management. These include (1)
nervous demeanor which can lead to stress-induced clinical complications, such as
hyperthermia; (2) lean body conformation with high surface-area-to-volume ratio,
which predisposes these dogs to hypothermia during anesthesia; (3) hematological
differences such as a higher packed cell volume and lower serum protein compared
with other dog breeds which may complicate interpretation of preanesthetic blood
work; (4) Impaired biotransformation of drugs by the liver resulting in prolonged
recovery from certain intravenous anesthetics, especially thiopental; and
increased risks of drug interactions. Safe anesthetic management of sighthounds
should include sedative premedication and appropriate use of analgesic drugs to
minimize perioperative stress. Thiopental, or any other thiobarbiturate, should
not be used in these dogs. Propofol, ketamine/diazepam combination, and
methohexital are recommended alternative intravenous anesthetics. Avoid
coadministration of agents that inhibit drug biotransformation, such as
chloramphenicol. Inhalation anesthesia using isoflurane is the preferred
anesthetic maintenance technique. Core body temperature should be monitored
closely and techniques to minimize hypothermia should be employed both during
anesthesia and into the recovery period.
PMID- 10193045
TI - Sedation and anesthesia of pet rabbits.
AB - Pet rabbits frequently become stressed when handled and may require sedation or
chemical immobilization for procedures such as blood collection, IV catheter
placement, radiography, deep ear cleaning, and dentistry. Common surgical
procedures requiring general anesthesia include spay, castration, gastrotomy,
cystotomy, and orthopedic procedures. Rabbits may be difficult to safely sedate
or anesthetize. Individual rabbits may have varying sensitivity to the depressant
effects of anesthetics. The apparent sensitivity of the rabbit's respiratory
center to anesthetic drugs and the narrow range between anesthetic and toxic
doses in this species add to the unpredictable character of rabbit anesthesia.
Furthermore, mortality following anesthesia and surgery in sick rabbits is
common. Strategically, safe anesthesia of rabbits must include the planning of
procedures so that anesthetic time is minimized. Clinicians must be on guard for
individual variation in response to drugs. Minimizing the use of cardiovascular
depressant agents, use of agents with a high therapeutic index, and careful
titration of doses to effect, along with thorough cardiorespiratory monitoring,
will permit attainment of appropriate anesthetic depth with the widest margin of
safety. This article presents several injectable and inhalant anesthetic
protocols that may assist in effective management of many types of rabbit
patient.
PMID- 10193046
TI - Anesthetic considerations for laser, laparoscopy, and thoracoscopy procedures.
AB - Laser surgery and laparoscopy are two relatively new surgical techniques gaining
popularity in veterinary medicine, which require special consideration when being
performed on the anesthetized patient. For laser surgery, consideration must be
given to the possibility of atmospheric contamination, inappropriate energy
transfer, eye injury, perforation of a vessel or anatomic structure, perforation
of the endotracheal tube, and fire. The primary concern with laparoscopy and
thoracoscopy is the creation of a pneumoperitoneum or pneumothorax, which can
result in (1) hypercarbia and inadequate ventilation, (2) poor cardiac output and
systemic blood pressure, and (3) gas embolism. To minimize complications,
patients should be placed on positive pressure ventilation, be well hydrated
before and during the procedure, and be thoroughly monitored (ECG, capnography,
pulse oximetry.
PMID- 10193047
TI - Prolonged anesthetic recovery.
AB - Failure to awaken, delayed awakening, and blunted responsiveness following
anesthesia constitute a continuum which must be recognized, diagnosed accurately,
and responded to appropriately. One must determine whether it is a normal
recovery for this animal or a pathological delay. A delayed recovery results in
continued depression of many organ systems. The possible etiologic factors, some
obvious, others quite obscure, must be considered quickly to provide the patient
with the best possible care. Diminished responsiveness is usually the result of a
complex interaction between multiple factors. A systematic approach to treatment
first begins by ensuring cardiac output, oxygenation, ventilation, and supportive
care in all patients. Then consider the potential causes for prolonged recovery
and either rule them out or treat them. First consider the potential causes for
central nervous system depression. Several commonly encountered medical
conditions enhance sensitivity to or decrease the elimination of anesthetic and
sedative agents. The astute clinician will be aware of the medical condition and
its impact on anesthetic drug effect and elimination to avoid prolonged
recoveries.
PMID- 10193048
TI - Dr. Angry and Mr. Smile: when categorization flexibly modifies the perception of
faces in rapid visual presentations.
AB - Are categorization and visual processing independent, with categorization
operating late, on an already perceived input, or are they intertwined, with the
act of categorization flexibly changing (i.e. cognitively penetrating) the early
perception of the stimulus? We examined this issue in three experiments by
applying different categorization tasks (gender, expressive or not, which
expression and identity) to identical face stimuli. Stimuli were hybrids: they
combined a man or a woman with a particular expression at a coarse spatial scale
with a face of the opposite gender with a different expression at the fine
spatial scale. Results suggested that the categorization task changes the spatial
scales preferentially used and perceived for rapid recognition. A perceptual set
effect is shown whereby the scale preference of an important categorization (e.g.
identity) transfers to resolve other face categorizations (e.g. expressive or
not, which expression). Together, the results suggest that categorization can be
closely bound to perception.
PMID- 10193049
TI - A generalized signal detection model to predict rational variation in base rate
use.
AB - The predominant models of rational behavior currently used to analyze a large
class of experiments imply that subjects neglect or place insufficient weight on
base rates when making probabilistic judgments. We argue that the evidence is
inadequate for this conclusion because the models make needlessly restrictive
assumptions about how base rates should be used. The restrictive assumptions stem
from a misuse of Bayes' rule that ignores specific aspects of how the proportions
arose. We develop a model of rational behavior that generalizes signal detection
theory to reflect the environment subjects routinely face and we reexamine the
relevant experimental literature. Variation observed in subjects' responses to
base rate information is explained by the present rational model more fully than
by extant models.
PMID- 10193050
TI - Lexical access in the production of pronouns.
AB - Speakers can use pronouns when their conceptual referents are accessible from the
preceding discourse, as in 'The flower is red. It turns blue'. Theories of
language production agree that in order to produce a noun semantic, syntactic,
and phonological information must be accessed. However, little is known about
lexical access to pronouns. In this paper, we propose a model of pronoun access
in German. Since the forms of German pronouns depend on the grammatical gender of
the nouns they replace, the model claims that speakers must access the syntactic
representation of the replaced noun (its lemma) to select a pronoun. In two
experiments using the lexical decision during naming paradigm [Levelt, W.J.M.,
Schriefers, H., Vorberg, D., Meyer, A.S., Pechmann, T., Havinga, J., 1991a. The
time course of lexical access in speech production: a study of picture naming.
Psychological Review 98, 122-142], we investigated whether lemma access
automatically entails the activation of the corresponding word form or whether a
word form is only activated when the noun itself is produced, but not when it is
replaced by a pronoun. Experiment 1 showed that during pronoun production the
phonological form of the replaced noun is activated. Experiment 2 demonstrated
that this phonological activation was not a residual of the use of the noun in
the preceding sentence. Thus, when a pronoun is produced, the lemma and the
phonological form of the replaced noun become reactivated.
PMID- 10193051
TI - Experimental pragmatics and what is said: a response to Gibbs and Moise.
AB - Gibbs and Moise [Gibbs, R., Moise, J., 1997. Pragmatics in understanding what is
said. Cognition 62, 51-74], present experimental results which, they claim, show
that people recognize a distinction between what is said and what is implicated.
They also claim that these results provide support for theories of utterance
interpretation (such as RELEVANCE Theory) which recognize that pragmatic
processes are involved not only in understanding what is implicated but also in
working out what is said (the 'explicature'). We attempted to replicate some of
these experiments and also adapted them. Our results fail to confirm Gibbs and
Moise's claims. Most significantly, they show that, under certain conditions,
subjects select implicatures when asked to select the paraphrase that best
reflects what a speaker has said. We suggest that our results can be explained
within the framework of RELEVANCE Theory (Sperber, D., Wilson, D., 1986.
RELEVANCE: Communication and Cognition. Blackwell, Oxford) if we assume that
subjects select the paraphrase that comes closest to achieving the same set of
communicated contextual effects as the original utterance. When an utterance
gives rise to a single strong implicature, subjects tend to select this as the
paraphrase that best reflects what is said; in other cases (for example in Gibbs
and Moise's stimuli) subjects tend to select the explicature.
PMID- 10193052
TI - Speakers' intuitions and pragmatic theory.
PMID- 10193053
TI - Scale-invariance as a unifying psychological principle.
AB - How can the classical psychological laws be explained and unified? It is proposed
here that scale-invariance is a unifying principle. Distributions of many
environmental magnitudes are observed to be scale invariant; that is, the
statistical structure of the world remains the same at different measurement
scales [Mandelbrot, B., 1982. The Fractal Geometry of Nature (2nd Edn.). W.H.
Freeman, San Francisco, CA; Bak, P., 1997. How Nature Works: The Science of Self
organized Criticality. Oxford University Press, Oxford, UK]. We hypothesise that
the perceptual-motor system reflects and preserves these scale invariances. This
allows derivation of several of the most widely applicable psychological laws
governing perception and action across domains and species (Weber's, Stevens',
Fitts' and Pieron's Laws). We suggest that these fundamental laws reflect
accommodation of the perceptuo-motor system to the scale-invariant physical world
and therefore have a common foundation.
PMID- 10193054
TI - Improving phonological awareness and word reading in a later learned alphabetic
script.
AB - This study examines the effects of phonological skill training on consonantal
phoneme deletion and word reading performance in two groups of adolescent Chinese
readers who were also literate in English. The research questions were: (1)
whether training would promote segmentation skills over and above years of
contact with the alphabetic (English) writing system, given an initial
logographic (Chinese) reading background; (2) whether improvements in
segmentation skills due to training would enhance word reading in the alphabetic
script. The participants were trained on phoneme counting, phoneme blending and
rime judgement with English materials over a period of two months. Resultant
changes in consonantal phoneme deletion and English word reading performance were
examined. Significant improvements in both activities due to training were
observed for the younger (mean age 12.7 years) but not the older (mean age 15.8
years) participants. Follow-up analyses showed that language proficiency might be
the factor underlying this age effect. Individual differences in phoneme deletion
uniquely predicted word reading for both age groups, although the relationship
tended to be stronger for the less proficient than the more proficient members.
These findings suggest that beyond years of normal reading instruction in the
alphabetic system, specialized segmentation training could still contribute to
promoting consonantal phonemic analysis that is not supported by the logographic
first-learned script. Moreover, improved phonological skills do lead to better
word reading in the later-learned writing system. Implications of the present
findings for second script reading instruction are considered.
PMID- 10193055
TI - Statistical learning of tone sequences by human infants and adults.
AB - Previous research suggests that language learners can detect and use the
statistical properties of syllable sequences to discover words in continuous
speech (e.g. Aslin, R.N., Saffran, J.R., Newport, E.L., 1998. Computation of
conditional probability statistics by 8-month-old infants. Psychological Science
9, 321-324; Saffran, J.R., Aslin, R.N., Newport, E.L., 1996. Statistical learning
by 8-month-old infants. Science 274, 1926-1928; Saffran, J., R., Newport, E.L.,
Aslin, R.N., (1996). Word segmentation: the role of distributional cues. Journal
of Memory and Language 35, 606-621; Saffran, J.R., Newport, E.L., Aslin, R.N.,
Tunick, R.A., Barrueco, S., 1997. Incidental language learning: Listening (and
learning) out of the corner of your ear. Psychological Science 8, 101-195). In
the present research, we asked whether this statistical learning ability is
uniquely tied to linguistic materials. Subjects were exposed to continuous non
linguistic auditory sequences whose elements were organized into 'tone words'. As
in our previous studies, statistical information was the only word boundary cue
available to learners. Both adults and 8-month-old infants succeeded at
segmenting the tone stream, with performance indistinguishable from that obtained
with syllable streams. These results suggest that a learning mechanism previously
shown to be involved in word segmentation can also be used to segment sequences
of non-linguistic stimuli.
PMID- 10193056
TI - Identifying objects in conventional and contorted poses: contributions of
hemisphere-specific mechanisms.
AB - Three experiments were designed to test the hypothesis that different mechanisms
are used to encode objects seen in unfamiliar contortions than are used to encode
objects seen in conventional poses. When a familiar non-rigid form (e.g. an
animal) is seen in a contorted pose, we hypothesize that object identification
may be achieved by (1) encoding the object's parts separately, (2) encoding the
spatial relations among the parts, and (3) matching these encoding to a stored
structural description. However, once this form has become familiar, its global
shape can be directly matched to information stored in memory. Based on the ideal
that 'categorical' spatial relations are encoded better by the left cerebral
hemisphere and are used in structural descriptions, we predicted a left
hemisphere advantage when one first encodes contorted poses; in contrast, based
on the idea that overall shapes are encoded better by the right hemisphere, we
predicted a right-hemisphere advantage for encoding the same shapes after they
are familiar. Three experiments confirmed these predictions, which supports the
hypotheses that different visual mechanisms operate in the recognition of
familiar and unfamiliar views of known non-rigid objects. Moreover, correlational
analyses between visual-field differences in several perceptual tasks (matching
whole pictures to names, body parts to the whole body, and judging categorical
spatial relations) revealed that the degree and lateralization of categorical
spatial encoding predicts the left hemisphere's initial advantage in the
identification of contorted shapes.
PMID- 10193057
TI - Taking on semantic commitments, II: Collective versus distributive readings.
AB - In earlier work, Frazier and Rayner (1990) provided evidence for a processing
principle termed the Minimal Semantic Commitment (MSC)hypothesis. In the present
study, we used the MSC hypothesis as a starting point in addressing the issue of
when to treat mental representations as vague versus determinate and ambiguous.
Given ambiguous representations, the MSC hypothesis predicts that the processor
will commit to one interpretation (the grammatical ambiguity hypothesis). On the
other hand, given a single underspecified representation, the MSC hypothesis
predicts that the processor will await disambiguating information before fully
committing to an interpretation (the vagueness hypothesis). In an experiment
designed to evaluate these hypotheses with respect to the representation of
distributivity, participants' eye movements were recorded as they read sentences
containing distributive or collective predicates that were either disambiguated
by a preceding adverb or left locally ambiguous by delaying the disambiguating
adverb until the end of the predicate. The results suggested that a semantic
commitment is made in locally indeterminate cases as evidenced by a significant
interaction of ambiguity and distributivity in first pass times, total times, and
regressions. If the difficulty of distributives simply reflected the difficulty
of postulating a distributive operator when evidence warranting it is
encountered, then no interaction would be expected. Hence we argue that the
distributive/collective distinction is treated as a matter of ambiguity rather
than as one of vagueness. In the absence of evidence for a distributive reading,
the processor commits itself to a collective reading sometime during the
processing of the predicate (before the disambiguation in our late disambiguation
examples). The findings are discussed in relation to recent linguistic work on
the representation of distributivity.
PMID- 10193058
TI - Developmental differences in sensitivity to semantic relations among good and
poor comprehenders: evidence from semantic priming.
AB - Semantic priming for category coordinates (e.g. CAT-DOG; AEROPLANE-TRAIN) and for
pairs of words related through function (e.g. BROOM-FLOOR; SHAMPOO-HAIR) was
assessed in children with good and poor reading comprehension, matched for
decoding skill. Lexical association strength was also manipulated by comparing
pairs of words that were highly associated with pairs that shared low association
strength. Both groups of children showed priming for function-related words, but
for the category co-ordinates, poor comprehenders only showed priming if the
category pairs also shared high association strength. Good comprehenders showed
priming for category-related targets, irrespective of the degree of prime-target
association. These findings are related to models of language development in
which category knowledge is gradually abstracted and refined from children's
event-based knowledge and it is concluded that in the absence of explicit co
occurrence, poor comprehenders are less sensitive to abstract semantic relations
than normal readers.
PMID- 10193059
TI - Salmonella java phage type Dundee--rise in cases.
PMID- 10193060
TI - Salmonella and eggs--working group asks for information.
PMID- 10193061
TI - AIDS and HIV infection in the United Kingdom: monthly report.
PMID- 10193062
TI - [Fungemia by lipophilic yeasts: a rarity or simply underestimated?].
PMID- 10193063
TI - [Bacteremia by Staphylococcus aureus: analysis of 311 episodes].
AB - BACKGROUND: The aim of this study was to set up the differences between
nosocomial and community acquired S. aureus bacteremia, to identify the features
of the patients at high risk of endocarditis and to define the characteristics of
the patients with methicillin resistant S. aureus (MRSA). METHODS: We
prospectively studied 311 cases of S. aureus bacteremia detected at our hospital
during a four-year period. RESULTS: Nosocomial acquisition of bacteremia was
found in 63% of the cases, 45% of which were caused by MRSA. Nosocomial bacteria
generally presented in older patients with more severe underlying conditions and
a higher prevalence of invasive procedures than patients with the community
acquired disease. Likewise, the primary focus of infection was identifiable in
most of the nosocomial episodes and mortality was also higher. Endocarditis
presented in 19% of the bacteremia episodes and almost 90% of patients with
endocarditis were intravenous drug users (IDU). The risk of endocarditis in this
group was 64% whereas it was only 3% in non-IDU patients. Overall mortality was
33% and mortality directly due to the bacteremia was 22%. CONCLUSIONS: IDU
patients were at high risk of endocarditis but most had a favourable outcome.
Bacteremia was community-acquired in these patients and they rarely presented
MRSA bacteremia. Patients with previous valvular diseases were at high risk of
endocarditis and had a high mortality. Non-IDU patients with community-acquired
bacteremia were at a low risk of endocarditis, regardless of whether a primary
focus of infection had been identified or not. Mortality was lower in this group
than in patients with nosocomial bacteremia and there were no cases of MRSA
bacteremia. Mortality was higher in patients treated with vancomycin than in
patients treated with other antibiotics active against S. aureus.
PMID- 10193064
TI - [The epidemiology of Q fever in the northern area of Huelva, Spain].
AB - OBJECTIVE: The aim of the present study is to know the prevalence, incidence and
clinical presentation of the acute Q fever in the north of the Huelva district.
METHODOLOGY: a) Prevalence: 1,654 serum were randomly collected from the health
district and distributed by their origin, age and sex. The methodology used was
the indirect immunofluorescence, Coxiella burnetii phase II as antigen. Were
regarded as positives those serum whose titles were equal or higher to 80; b)
Incidence: prospective study of every case treated in hospital during 1996-1997
plus every referred patient from the different "Health Centers". An acute case of
Q fever was established as a feverish syndrome of more than 2 days plus a title
equal or higher to 320 against C. burnetti phase II antigen, and c) Clinical
data: all the patients were clerked and similar form was filled up including the
following items: pneumonia, hepatitis, headache, persistent fever, etc. RESULTS:
a) Prevalence: it was 5.08%, more frequent in men than in women; b) Incidence: 21
new cases over two years, an incidence of 12.70 cases per 100,000 population, and
c) CLINICAL PRESENTATION: feverish syndrome plus hepatitis in 100% of the cases,
just two pneumonia were recorded and in 4 cases the clinical picture was
associated to immunological symptoms with persistent fever. CONCLUSION: A
discrepancy between incidence and prevalence has been pointed out which makes us
think that the majority of the Q fever cases in this area debut as a self
restricted feverish syndrome which does not require specialized treatment.
PMID- 10193065
TI - [Invasive aspergillosis in patients with human immunodeficiency virus infection
diagnosed by necropsy: the contribution of 4 cases and review of the literature].
AB - BACKGROUND: Invasive aspergillosis is an infrequent clinicopathological entity
which is difficult to diagnose (since it requires tissue samples, normally of the
lung where the pathogenic effect of the fungi may be seen) and thus an important
number of cases are not found until necropsy. In patients with human
immunodeficiency virus (HIV) infection the real incidence has not been clearly
defined and may be higher than reported. MATERIAL AND METHODS: We herein present
a series of necropsy reviews performed over a five year period (January 1993 to
December 1997) in the Hospital Universitario San Carlos in Madrid (Spain) in
patients with HIV infection. In the patients who presented invasive aspergillosis
a collection protocol of clinical, analytical and radiologic data was undertaken.
RESULTS: Over this period necropsic studies were performed in 23 patients with
HIV infection. Of these 4 (17.3%) presented invasive aspergillosis; 3 with
disseminated involvement. Premortem diagnosis was not performed in any of the
cases. The risk factors included: 3 had a CD4 count of less than 50, two were
receiving glucocorticoids and only 1 had severe neutropenia. In 2 another
opportunistic lung infection was also observed. CONCLUSIONS: Invasive
aspergillosis is an entity witch is found on autopsy with relative frequency in
patients with HIV infection with severe immunodepresion. Other opportunistic
infections may also coincide and it may not be associated with neutropenia,
glucocorticoid treatment, which are considered as classical risk factors for
invasive aspergillosis.
PMID- 10193066
TI - [Usefulness of polymerase chain reaction (PCR) in the diagnosis of meningococcal
meningitis].
AB - BACKGROUND: The aim of this work was to evaluate the applicability of polymerase
chain reaction (PCR) in the microbiological diagnostic of meningococcal
meningitis as compared with the conventional methods (Gram stain and culture).
METHODS: One hundred and fifteen cerebrospinalis fluid samples from 115 patients
with suspicious symptoms of meningitis were studied. 47 of them belonged to
patients suspicious for meningococcal disease; 28 to patients with bacterial
meningitis of other infectious etiologies; 10 to patients with meningitis showing
lymphocytic pleocytosis and 30 to patients with an unconfirmed meningitis. The
cerebrospinalis fluid samples were processed for culture by standard procedures
and by PCR according to the method described by Newcombe et al for peripheral
blood samples. RESULTS: Thirty five out of 39 patients suspicious of
meningococcal meningitis were microbiologically confirmed, being 22 culture and
PCR positive, 3 microscopically and PCR positive, 1 only microscopically
positive, and 9 positive only by PCR. By using PCR methodology, the number of
confirmed diagnostics of meningococcal meningitis increased in a 23% as compared
to those obtained by microscopic observation and culture. Sensitivity,
specificity, predictive positive value and predictive negative value were 87.1,
98.7, 97.1 and 94.1 respectively for the PCR method. CONCLUSIONS: Our results
indicate that PCR can be used on routine basis as a complementary technique to
the standard laboratory procedures for diagnosis of meningococcal meningitis.
PMID- 10193067
TI - [Adherence to very active antiretroviral treatment: impact of individualized
assessment].
AB - BACKGROUND: To determine if the intervention of individual advice improves
adherence and effectiveness to highly active antiretroviral therapy. METHODS:
Randomized open trial. Patients treated with zidovudine + lamivudine + indinavir
were assigned (2/1) to conventional care or individual advise. Individual advise
consists in adaptation to treatment to patient style of live and detailed
information of therapy. Adherence were estimated with structured interview and
pillo counts and were considered correct when more than 90% of prescribed drugs
were taken. RESULTS: Patients 170, conventional care: 110 and IA: 60. FOLLOW-UP:
24 weeks. Baseline characteristics were similar in both groups. Correct adherence
were estimated in 52.7% of conventional care and in 76.7% of individual advise (p
= 0.002, relative risk: 1.45; CI 95%: 1.16-1.82). Undetectable viral load (NASBA
< 50 copies/ml) in 54.5% of conventional care and in 65% of individual advise (p
= 0.18, relative risk: 1.19; CI 95%: 0.93-1.53). Reduction of viral load in the
conventional care group 1.02 +/- 0.5 log10/ml, and in the individual advise group
1.98 +/- 0.7 log10/ml. CONCLUSION: The individual advice improve adherence with a
tendency to improve effectiveness of highly active antiretroviral therapy.
PMID- 10193068
TI - [Comparison between centrifugation and sedimentation prior to cultures in the
isolation of cytomegalovirus in the urine of renal transplant recipients].
AB - BACKGROUND: To compare the capacity of conventional centrifugation and
spontaneous sedimentation to detect the presence of cytomegalovirus (CMV) in
urine samples. MATERIAL AND METHODS: We studied urine samples from 45 renal
transplant recipients. After decontamination half of each sample was centrifuged
(1,500 rpm for 10 minutes) and the other half was allowed to sediment at room
temperature for 30 minutes. From the supernatant of each of these 250 microliters
was inoculated in a shell-vial (MRC-5). Cultures were incubated for 48 hours at
37 degrees C and stained by an indirect immunofluorescence assay. The samples
considered totally toxic were re-inoculated after dilution 1:1 with maintainance
medium. RESULTS: Of 845 urine samples analyzed, 743 (88%) were negative and 102
(12%) positive. 66 (7.8%) were considered toxic: 35 (4.1%) partially toxic and 31
(3.6%) totally toxic. Of the centrifuged urine samples 86.2% were positive
against 98% of the sedimented samples (p = 0.004). Of the 31 samples considered
totally toxic, 17 (2.2%) corresponded with negative urine samples and 14 (13.7%)
with positive samples. Off these, 12 (85.7%) were detected in centrifuged samples
and 2 (14.3%) in sedimented samples (p = 0.001). CONCLUSIONS: The percentage of
toxicity in the urine samples was low (7.8%) which does not seem to suggest the
need for systematic dilution of all samples. The sedimentation process enabled us
to detect a greater number of urine samples positive for CMV with a lower rate of
toxicity of the monolayers. The use of this process would reduce the number of
samples requiring reinoculation.
PMID- 10193069
TI - [Disease from Mycobacterium kansasii].
PMID- 10193070
TI - [Abscess of the abdominal wall].
PMID- 10193071
TI - [Cutaneous infection following participation in the "killing of the pig"].
PMID- 10193072
TI - [Arthritis/infectious osteomyelitis from a human bite].
PMID- 10193073
TI - [Efficacy of intralesional treatment with antimonials in four cases of cutaneous
leishmaniasis].
PMID- 10193074
TI - [Splenic infarction in a patient with anticardiolipin antibodies and
leptospirosis].
PMID- 10193075
TI - [Disseminated tuberculosis manifesting as a clinical picture of sacroiliitis].
PMID- 10193076
TI - [Cellulitis from Acinetobacter].
PMID- 10193077
TI - [Colon involvement as a form of presentation of visceral leishmaniasis in an AIDS
patient].
PMID- 10193078
TI - [Large silent abscess in the leg by Escherichia coli].
PMID- 10193079
TI - [Empyema and spontaneous bacterial peritonitis in a cirrhotic patient by
Streptococcus agalactiae].
PMID- 10193080
TI - [Diagnosis of catheter infection].
PMID- 10193081
TI - [The monitoring, evaluation and programming of mental health departments. A
regional system of indicators. The Evaluation Center, the QUALI DSM Project, the
Lazio region].
PMID- 10193082
TI - [Advise to pregnant women on the question of "home childbirth--yes or no?" What
are the criteria for a planned home delivery?].
PMID- 10193083
TI - [Prevention and management of alcohol problems. Brief intervention by the family
physician--a simple and efficient method].
AB - Brief intervention, early intervention and secondary prevention are terms used in
modern treatment of alcoholism that are gaining importance. By "intervention" in
this connection is meant a "mediatory intervention". In various national and
international projects, such an intervention on the part of the general
practitioner has led to a significant reduction in the amounts drunk by patients
abusing alcohol, and has thus contributed to the prevention of alcohol
dependence. The present paper describes what is meant by the term short
intervention, and describes the chances offered by this type of treatment in the
area of basic medical care. Special attention is drawn to the technique of
motivational interviewing and the FRAMES concept.
PMID- 10193084
TI - [Hospitalization of alcoholics is of primary importance. Interview].
PMID- 10193085
TI - [Care of tumor patients with biliary-duodenal drainage by the family physician.
Treatment of extrahepatic biliary obstruction].
AB - Ambulatory care of patients with tumors of the biliary system and pancreas
undergoing bilioduodenal drainage for obstructive jaundice is increasingly being
provided by the family doctor in cooperation with an endoscopy center. The
greatest risk for the patient is the development of acute cholitis caused by
blockage of the endoprosthesis with the need for immediate replacement of the
latter. Apart from the clinical examination, laboratory data and ultrasonography
are often required to establish the diagnosis and enable an adequate assessment
of the bile flow situation to be made. Additional diagnostic procedures (e.g.
endosonography and computed tomography) are needed only for the primary
diagnostic work-up. The data obtained from our patients show that family doctors
are well attuned to the leading symptoms, and that delays in acting on suspected
obstruction of the biliary stent rarely occur.
PMID- 10193086
TI - [Reactive arthritis. Diagnosis, differential diagnosis and therapy].
PMID- 10193087
TI - [Herbal medicine--taking a position. Effectiveness and usefulness of herbal
preparations].
AB - During the discussion on the elimination of certain groups of drugs and disorders
from the list of obligatory services to be remunerated by state health
insurances, vague, undefined terms such as "controversial" are being applied to
phytopharmaceuticals and their fields of application. This may be traced back to
an ignorance and global rejection of available scientific documentation. The
rational background of modern phytopharmaceuticals are discussed.
PMID- 10193088
TI - [The usefulness of hydrogastric ultrasonography in the detection of neoplastic
lesions of the gastric wall].
AB - Forty patients endoscopically diagnosed of different gastric neoplastic lesions
were explored by hydrogastric ultrasonography to evaluate the usefulness of this
method in the detection of such lesions and to analyze the characteristics of the
ultrasonographic images and their correlation with the anatomopathologic
findings. The sensitivity of the detection of the lesions was 87.5% being close
to 100% in those located in the antrum, showing the body and fundus more
difficulties due to gas and the costal ribcage. A clear correlation was observed
between the ultrasonographic images and the anatomographic findings. It was
concluded that this may be a complementary technique to gastroscopy in the
diagnosis of sumucosal lesions and extrinsic compressions of the gastric wall.
The infiltration of the wall may be delimited in neoplastic lesions and thus may
contribute to correct T stratification of the tumor, although this should be
confirmed in further studies.
PMID- 10193089
TI - [The usefulness of transjugular hepatic biopsy in the evaluation of liver disease
in candidates for heart transplantation].
AB - Heart transplantation is a universally accepted procedure in the treatment of
terminal heart diseases. However, the presence of advanced liver disease in the
potential receptors represents a contraindication for heart transplantation. On
the other hand, the true diagnosis of liver disease not secondary to heart
disease may be difficult requiring confirmatory liver biopsy. Nonetheless,
percutaneous liver biopsy may be difficult to perform due to presence of
coagulation alterations, marked dilatation of the hepatic veins, etc. The aim of
this study was to evaluate the efficacy and safety of transjugular hepatic biopsy
in the presence of severe coagulopathy in potential heart transplantation
receptors with suspicion of liver disease and contraindication of percutaneous
liver biopsy. Over a 9-year period, 350 potential heart transplantation patients
were evaluated. In 23 patients (6.7%) transjugular hepatic biopsy was performed
with aspiration needle followed by a hemodynamic study in 17 cases. The
transjugular hepatic biopsy was completed in 22 cases (95.6%) with adequate
material for the diagnosis being obtained in 21 (91.3% of the total cases
indicated). Histologic study showed significant inflammatory infiltrates or
alteration of the hepatic architecture in 4 patients (18%), all being positive
for some viral markers (AgHBs or anti-HCV). The obtaining of a certain histologic
diagnosis modified the consideration of liver disease as a definitive
contraindication and allowed the performance of heart transplantation in 17
patients (73.9%). No complications were observed in association with the
procedure. The transjugular hepatic biopsy is a feasible, effective and safe
alternative for obtaining liver tissue in patients under evaluation for heart
transplantation with suspicion of severe liver disease. The establishment of a
correct histologic diagnosis may modify the clinical decision in an important
number of patients.
PMID- 10193090
TI - [Digestive alterations in cystic fibrosis. Retrospective study of a series of 46
adult patients].
AB - The clinical histories of 46 adult patients (24 men and 22 women, mean age 20.6
+/- 5.1 years) diagnosed of cystic fibrosis were reviewed evaluating the
digestive alterations. The age at diagnosis of cystic fibrosis was 5.63 +/- 5.3
years (range: newborns-19 years). The initial diagnosis was established by ileus
meconium, in four, lung disease in 15, steatorrhea in 12, lung disease and
steatorrhea in 13 and following the diagnosis of cystic fibrosis in siblings in
two. Four patients presented ileus meconium, nine occlusive syndrome of the
distal intestine, 42 steatorrhea (20 severe, 12 moderate and 10 mild), with the
severity of the steatorrhea not being associated with the severity of the
respiratory insufficiency. Two patients presents rectal prolapse, five
gastroesophageal reflux syndrome (four with hiatal hernia), six cholelithiasis,
one recurrent pancreatitis without detection of biliary lithiasis, one neonatal
cholestasis and 10 malnutrition (five severe and five moderate) fundamentally in
relation to the severity of the lung disease and, to a lesser degree, liver
disease. In 10 patients chronic liver disease was diagnosed corresponding to
established cirrhosis in seven, indicating liver transplantation in two. In most
cases, the liver disease was already manifest in adolescence even in the
cirrhotic stage. Cholangiography by magnetic resonance was useful in the study of
liver disease showing abnormalities which imitated primary sclerosing
cholangitis. Treatment with ursodesoxicholic acid at a dosis of 20 mg/kg/day led
to a significant decrease in the transaminase values and overall of
gammaglutamyltranspeptidase but did not avoid complications in the cirrhotic
stages. Genetic studies performed in 36 patients detected the delta F508 mutation
in 69.4%, being found in almost all of the patients with ileus meconium,
occlusive syndrome of the distal intestine, liver disease, cholelithiasis and
malnutrition.
PMID- 10193091
TI - [Spontaneous bacteremia due to Salmonella hadar in liver cirrhosis with
transjugular intrahepatic portosystemic shunt].
AB - Bacteriemia is a frequent infection in patients with hepatic cirrhosis, which is
associated with a high mortality. Spontaneous bacteriemia is generally caused by
gramnegative bacilli. We present an episode of Salmonella hadar's spontaneous
bacteriemia in a patient with cirrhosis of the liver and transjugular
intrahepatic portosystemic shunt. The role of the prosthesis in the pathogenesis
of bacteriemia in hepatic cirrhosis is discussed.
PMID- 10193092
TI - [Primary intestinal T lymphoma with massive eosinophilia].
AB - Primary intestinal T lymphoma with eosinophilia is an infrequent tumour. Its
rarity account for the paucity of similar cases recorded in the literature. It
affects predominantly middle-aged men and may be associated with ulceration,
fistula formation and intestinal perforation with an abdominal mass. Lesions of
the intestine with massive tissue eosinophilia may be a difficult diagnostic
problem, but this entity displays distinctive histological features. The presence
of intense tissue eosinophilia is a T-cell dependent lymphomas response. We
describe a case of T lymphoma involving small intestine with massive
eosinophilia.
PMID- 10193093
TI - [Cryoglobulinemia following liver transplantation for cirrhosis secondary to
hepatitis C virus infection].
AB - Hepatitis C virus (HCV) infection has been linked with some extrahepatic
immunologic abnormalities. Cryoglobulinemia is one of the most frequently
reported. Nevertheless, there are only a few reports of cryoglobulinemia in the
setting of liver transplantation. More studies are needed to clarify the
frequency of post-OLT cryoglobulinemia in patients with HCV-related cirrhosis and
its impact on OLT outcome. A case of a patient who underwent liver
transplantation because of HCV end-stage liver disease and in whom
cryoglobulinemia appeared 3 years after transplantation is reported. Treatment
with cyclophosphamide and steroids was attempted but patient died of septicemia 3
years after liver transplantation.
PMID- 10193094
TI - [The debut of Crohn's disease as a gastrocolic fistula].
AB - The case of a 66-year-old women admitted for the study of chronic diarrhea and an
important deterioration in her general state is reported. Following the study
undertaken the presence of a gastrocolic fistula was observed without clarifying
the nature of the same thereby leading to surgical treatment. Anatomopathologic
analysis confirmed the presence of a gastrocolic fistula in relation to Crohn's
disease. The origin of these fistulas is usually neoplastic and the presentation
as a complication of an inflammatory disease is very infrequent.
PMID- 10193095
TI - [The organization of a digestive endoscopy unit].
PMID- 10193096
TI - [Zollinger-Ellison syndrome].
PMID- 10193097
TI - [Hepatoxicity by enalapril].
PMID- 10193098
TI - [Guillain-Barre syndrome in a patient with ulcerative colitis in remission].
PMID- 10193099
TI - [Bacteremia by Streptococcus bovis in a patient with chronic liver disease
without colon disease].
PMID- 10193100
TI - [Accessory spleen in hepatic cirrhosis: incidence and characteristics of Doppler
ultrasonography duplex color].
PMID- 10193101
TI - Reproductive toxicity of occupational mercury. A review of the literature.
AB - OBJECTIVES: This paper aims to give the dental practitioner insight into the
potential reproductive effects of handling dental silver amalgam, c.q. mercury.
DATA SOURCES: Experimental studies on animals, case reports and epidemiologic
studies. STUDY SELECTION: Experimental animal studies show high
doses/concentrations of mercury to increase the risk of reproductive disorders,
e.g. infertility, spontaneous abortion, stillbirth and congenital malformations.
Some case reports suggest an association between the disorders in humans and high
levels of mercury. Therefore, the present article reviews epidemiological studies
on the relationship between occupational exposure to mercury, mainly as vapour in
the dental practice, and females' procreative ability. Studies concerning the
reproductive effects of males' occupational mercury body burden are scarce. The
reproductive risk of patients' mercury uptake from silver amalgam fillings is
assessed. CONCLUSIONS: It seems warranted to conclude that negative reproductive
effects from exposure to mercury in the dental office are unproven, but safe
levels have not been established. Seemingly problems are unlikely to occur,
unless a poor hygiene causes the mercury concentration in the air to exceed
females' time-weighted long-term Threshold Limit Value (TLV). Consequently, in
view of the in general low amounts of mercury stemming from dental amalgam
fillings, the population at large is at even less risk than dental staff. The
effects of occupational elemental mercury concentrations lower than the TLV on
the menstrual cycle, conception, male fertility and children's behaviour need,
however, more research.
PMID- 10193102
TI - Effects of direct resin pulp capping techniques on short-term response of
mechanically exposed pulps.
AB - The aim of this in vivo study was to evaluate the effects of direct pulp capping
techniques on the short-term response of mechanically exposed pulps using three
commercially available adhesive resin systems. Class V cavities were prepared on
the facial surface of 200 intact monkey teeth. Pulps were exposed with a carbide
bur on the cavity floor. Each exposed pulp was capped with one of three
commercially available adhesive resins or a hard-setting calcium hydroxide liner.
All cavities were sealed with an adhesive resin, and were restored with hybrid
resin composites. Inflammatory cell infiltration and dentine bridging of the
exposed pulp and protrusion of the exposed pulp tissue into the cavities were
evaluated histologically at 3, 7, 14, 30 and 60 days. A slight inflammatory cell
infiltration was the principal reaction of the exposed pulp. The exposed area was
occluded over time with dentine bridging in all groups. However, a protrusion of
pulp tissue into the prepared cavity was observed at the periphery of the exposed
area in all groups. These tissues communicated with the underlying pulp. The
incidence of pulp tissue protrusion was ranked in order of increasing severity:
Liner Bond II < Dycal < Bondwell LC = Super Bond C&B. Following pulp capping of
the mechanical exposures, slight inflammation was the main reaction. Exposures
became occluded with a dentine bridge over time. However, the protrusion of pulp
tissue into cavities varied, depending on the materials used.
PMID- 10193103
TI - The effect of dentine location and tubule orientation on the bond strengths
between resin and dentine.
AB - This study determined the influence of dentine structure on the micro-tensile
bond strengths between resin and dentine of two different dentine adhesive
systems (Single Bond, 3M Dental Products, St Paul, MN; MF-102 (experimental self
etching primer), GC Corporation, Tokyo, Japan). The study was separated into two
main parts: bond strength measurement and investigation of the bonding interface.
Twenty-two human premolars were used for the bond strength measurement. Each
tooth was cut vertically, separating the tooth into mesio-distal halves. One half
of the tooth was used to bond to a surface perpendicular to the dentinal tubules
and other half to bond to a surface parallel to the tubules. For each half, six
locations of dentine were bonded. Each material was used in accordance to the
manufacturer's directions. Cylindrical hourglass-shaped specimens of 1.2 mm
diameter at the bonded interface were manufactured. The bonds were stressed in
tension at a crosshead speed of 1 mm/min. Mean bond strengths were compared using
LSD, one-way ANOVA, and Student's t-test. The fractured surfaces were examined
under a scanning electron microscope, and the frequency of fracture modes was
compared using the Kruskal-Wallis and Mann-Whitney U tests. For the investigation
of the bonded interface, four teeth were prepared by the same procedure used for
the bond test specimens. The bonded interfaces were observed after an acid-base
treatment or fracturing across the bonded interface, prior to investigation with
a field-emission scanning electron microscope. For Single Bond, the bond
strengths for mid-root dentine were significantly lower than for other locations
(p < 0.05). For MF-102, there was no significant difference for all locations (p
> 0.05). MF-102 bonded well to all locations of dentine while Single Bond showed
a porous zone at the base of the hybrid layer. The bonds were not influenced by
tubule orientation. The results indicate that the bond for Single Bond may be
affected by its ability to penetrate demineralised dentine in different locations
of a tooth. The self-etching primer of MF-102 produces a good bond and is
independent of the position on the tooth.
PMID- 10193104
TI - Stiffness, elastic limit, and strength of newer types of endodontic posts.
AB - OBJECTIVES: To determine the stiffness, elastic limit, and strength of a
selection of endodontic posts recently introduced onto the market. METHODS:
Endodontic posts of zirconia (Biopost, Cerapost), titanium (PCR), and carbon
fiber (Composipost) were cemented in a brass block and loaded at an angle of 45
degrees in an Instron Testing Machine. From the recorded relationship between
force and deflection the three mechanical properties were determined (n = 10 in
each group). RESULTS: The ceramic posts were very stiff and strong, with no
plastic behavior. The PCR post was as strong as, but less stiff than, the ceramic
posts. Composipost had the lowest values for stiffness, elastic limit, and
strength of the posts investigated. CONCLUSION: The posts under investigation
differed significantly with respect to mechanical properties.
PMID- 10193105
TI - Water sorption and colour stability of composites containing the antibacterial
monomer MDPB.
AB - OBJECTIVES: Previously, we have reported that composites incorporating the newly
developed antibacterial monomer methacryloyloxydodecylpyridinium bromide (MDPB)
inhibited bacterial growth and plaque accumulation on their surfaces without
releasing antibacterial components, and that the antibacterial effect was not
lost even after ageing in a wet environment for a long period. The purpose of
this study was to investigate the influence of the incorporation of MDPB on the
water sorption characteristic and colour stability of Bis-GMA based composites.
METHODS: Cured disc-shaped specimens of composites containing 0.4% or 0.5% MDPB
were fabricated, and water uptake, the diffusion coefficient and the surface
contact angle for water were determined. Discoloration of MDPB-containing
composites was evaluated after immersion in water at 37 degrees C and 60 degrees
C for 4 weeks and compared with that of the control composite without MDPB.
RESULTS: There were no significant differences in water uptake, diffusion
coefficient and contact angle between the control and MDPB-containing composites.
Although composites incorporating MDPB showed greater discoloration than the
control when maintained at 37 degrees C, no difference was found after 4 weeks of
immersion in water at 60 degrees C. CONCLUSIONS: Incorporation of small amounts
of the antibacterial monomer MDPB showed no influence on the water sorption
characteristic and affected a little the colour stability of the Bis-GMA based
composite, causing rapid discoloration.
PMID- 10193106
TI - Development and evaluation of a low erosive blackcurrant juice drink in vitro and
in situ. 1. Comparison with orange juice.
AB - OBJECTIVE: The aim of this study was to determine whether an experimental
blackcurrant juice drink with added calcium was less erosive to enamel both in
vitro and in situ compared with a proprietary orange juice product. METHODS: The
study was a single centre, blind, randomised, placebo controlled three cell
crossover design. An intra oral appliance capable of retaining one enamel sample
in situ was constructed and worn by 12 volunteers. The drinks under test were
orange juice, the experimental blackcurrant juice drink with calcium and water.
Drinks were consumed as 250 ml volumes four times during the working day under
supervision for 15 days. The same methodology was modelled in vitro. Measurements
of enamel loss were made by profilometry. RESULTS: Water, the experimental
blackcurrant juice drink and orange juice produced 0.19, 0.41 and 2.54 microns
loss of enamel respectively in situ and 0.0, 5.2 and 22.18 microns loss of enamel
respectively in vitro. All differences between pairs of drinks in situ and in
vitro were statistically significant. CONCLUSIONS: Data using this model in situ
were only available for orange juice and this was therefore considered as a
positive control with water a placebo control. The results have demonstrated that
the experimental blackcurrant juice drink with calcium is markedly less erosive
than orange juice, particularly and importantly in situ. The experimental
blackcurrant juice drink has limited erosive potential to teeth and deserves
further comparative investigation and development as a low pH fruit drink for
public consumption.
PMID- 10193107
TI - Application of bis-eugenol to a zinc oxide eugenol cement.
AB - OBJECTIVES: To assess the usefulness of dimerized eugenol (bis-eugenol) in
dentistry, the physical properties of zinc oxide eugenol cement (ZOE) with bis
eugenol and the cytotoxicity of bis-eugenol were studied. METHODS: Setting time,
compressive strength, solubility and disintegration of ZOE cement with bis
eugenol according to the specifications of JDMAS315 were evaluated. The
cytotoxicity of bis-eugenol and eugenol toward two different cell types, HGF (a
primary culture of human gingival fibroblast) and HSG (a human epidermoid
carcinoma cell line derived from a salivary gland) was evaluated by the MTT test
and in terms of cell survival. RESULTS: Addition of bis-eugenol to ZOE did not
decrease the physical properties when employed at the ratio of 9:1 or 6:1 (liquid
ND:bis-eugenol, w/w). Bis-eugenol was less toxic than eugenol in the cell culture
tests. CONCLUSIONS: The results of this assay demonstrated that bis-eugenol is
useful in ZOE.
PMID- 10193108
TI - Investment strength as a function of time and temperature.
AB - OBJECTIVES: The purpose of this investigation was to evaluate and compare the
compressive strength characteristics of selected investments and to determine if
these change as a function of time and temperature after mixing. METHODS: Two
phosphate-bonded investments and one gypsum-bonded investment were selected and
288 cylindrical specimens were fabricated (n = 9). Baseline compressive strength
values were determined for each material at room temperature and compressive
strength measurements were made for all materials at 700 degrees C, and at 872
degrees C only for phosphate-bonded investments. Each material was tested at 2,
6, 12, and 24 h after mixing. Specimens were heated at 15 degrees C/min and heat
soaked for 5 min in a burnout oven at the applicable testing temperature. They
were transferred to a preheated chamber on an Instron testing machine and
subjected to a compressive load at a crosshead speed of 2 mm/min until failure.
The resulting strength data are presented in MN/m2. RESULTS: The gypsum-bonded
investment did not exhibit marked differences in strength as a function of either
time or temperature. The phosphate-bonded investments, on the other hand,
demonstrated considerable changes in compressive strength and differed in
compressive strength characteristics at 700 degrees C and 872 degrees C
respectively. CONCLUSIONS: At elevated temperatures, all materials approximated
peak strength 2 h after initial mixing. At room temperature, the phosphate-bonded
investments in this study were not significantly stronger than the gypsum-bonded
investment material. However, they exhibited increased compressive strength as a
function of time and temperature that was considerably higher than that exhibited
by the gypsum-bonded investments.
PMID- 10193109
TI - The effect of curing regime on the release of hydroxyethyl methacrylate (HEMA)
from resin-modified glass-ionomer cements.
AB - This study investigated the effects of degree of cure and specimen maturation on
the release of HEMA from four resin-modified glass-ionomer cements. Disc
specimens were light-cured for either the manufacturers' recommended time (MRT)
for that material, or were under-cured (irradiated for 0.5 MRT), over-cured (1.5
MRT) or allowed to dark-cure (0 MRT). Specimens were matured in the mould at 37
degrees C until set or for 10 min, 40 min or 24 h prior to immersion in distilled
water (at 37 degrees C) for 4 h. The HEMA release was determined by measuring the
HEMA concentration in the storage water by HPLC. Vitremer, Fuji II LC and Fuji
Lining LC set without light-curing (0 MRT) in less than 6 min and these specimens
released low levels of HEMA (approximately 1, 7 and 4% of the included HEMA,
respectively). Dark-cured Vitrebond took 15 min to set and the HEMA release was
high (approximately 50% of the included HEMA) indicating that the material had
only set by the acid-base reaction. HEMA release from light-cured Vitremer or
Vitrebond was not affected by under- or over-curing but release from Fuji II LC
was reduced by over-curing (1.5 MRT). Under-curing Fuji Lining LC caused a
significant increase in HEMA release. Specimen maturation times of 10 min, or
longer, had little effect on the measured HEMA release. All the materials
released HEMA into their storage solutions. In order to minimise HEMA release,
resin-modified glass-ionomers should always be cured for at least the
manufacturers' recommended time at thicknesses no greater than the maximum
recommended.
PMID- 10193110
TI - Effect of sterilisation methods on the structural integrity of artificial enamel
caries for intra-oral cariogenicity tests.
AB - Enamel blocks bearing artificial caries are used in intra-oral appliances for
cariogenicity tests. These blocks are often sterilised to prevent the possibility
of cross-infection via this route. This study therefore aimed to determine the
effect of sterilisation methods on the structural integrity of artificial enamel
caries used for intra-oral cariogenicity tests. Four experimental groups were
devised. Ten bovine incisors were used in each group. Artificial caries was
produced in each tooth which was subsequently cut into two halves. One half of
each tooth was reserved as control while the other was sterilised. The four
groups were subjected to respective sterilisation methods: gamma irradiation
(approximately equal to 25 KGy), steam autoclaving (121 degrees C for 15 min),
sodium hypochlorite (12% w/v for 24 h) and povidone-iodine (7.5% w/v for 24 h).
The control and sterilised specimens in each group were examined for microbial
growth after incubation in nutrient broth for up to 7 days at 37 degrees C under
aerobic and anaerobic conditions. Mineral loss and lesion depth were quantified
from microradiographs of sections from control and sterilised specimens using
transverse microradiography. Data were analysed statistically by paired Student's
t-test. Microbial growth was observed only in control specimens. Gamma
irradiation and NaOCL caused cream discolouration and bleaching of the enamel
surface, respectively. Autoclaving, sodium hypochlorite and povidone-iodine
resulted in further demineralisation of the lesions. The four sterilisation
methods were all effective sterilants for artificial caries. However, gamma
irradiation appears the most acceptable method considering the more adverse
effects of the other methods with regards to cariogenicity tests.
PMID- 10193111
TI - British Isles symposium on the future of dental clinical skills training.
AB - A symposium on the future of dental clinical skills training is reported.
Abstracts of the symposium presentations review the current and future use of
simulation in dental education, future skills training in the creation of new
dentists, equipment and methods for simulation, the transition from simulation to
clinical practice and recent developments in simulation employing new
technologies. The report concludes that simulation will continue to have an
important, probably increasing role in dental education, and that further
developments in clinical skills training should be sensitive to changing patterns
of dental disease and opportunities of provide clinical instruction.
PMID- 10193112
TI - [Screening for alpha 1-antitrypsin deficiency is still justified. Early discovery
prevents pulmonary emphysema].
PMID- 10193113
TI - [The concept of handicap must be discussed in psychiatry!].
PMID- 10193114
TI - [The sterilization wave in Peru, how does the Medical Society act?].
PMID- 10193115
TI - [On virility, eroticism and sexuality].
PMID- 10193117
TI - [Unclear on treatment of tennis elbow].
PMID- 10193116
TI - [Many questions following a report on dextropropoxyphene].
PMID- 10193118
TI - [Controlled trials of surgical treatment of mental diseases?].
PMID- 10193119
TI - [A new method for detecting congenital hearing disorders. Infants are screened by
measuring otoacoustic emissions].
AB - Despite various infant screening programmes, congenital hearing deficit is
normally detected too late. However, the measurement of otoacoustic emissions
(OAE) has now proved to be an effective means of assessing neonatal hearing. The
article consists in an outline of both international and Swedish experience of
universal neonatal screening programmes using OAE testing. Since universal OAE
screening was introduced at University Hospital, Linkoping, in September 1995,
some 6,000 infants have been tested. During the first two years 98.5 per cent of
the children participated. Satisfactory bilateral OAE test results were obtained
in 97.1 per cent of cases. Where further investigation was necessary, it took the
form of auditory brainstem response (ABR) testing during natural rest, or full
diagnostic ABR testing under general anaesthesia.
PMID- 10193120
TI - [Prolactin--a hormone with many effects].
PMID- 10193121
TI - [Male depression--stress reaction combined with serotonin deficiency?].
AB - An educational programme on depressive disorders, given to general practitioners
on the Swedish island of Gotland, resulted in a statistically significant
reduction of the suicide rate among women, though that among men was virtually
unaffected. Further analysis showed the profile of depression among men to differ
from that among women, the male pattern typically being more characterised by
irritability, aggressiveness, acting out, antisocial behaviour and alcohol abuse,
and reduced impulse control and stress tolerance. Predisposition to affective
disorders, suicide and alcoholism seems to be genetically determined. The
syndrome, which is not easily recognised and is seldom properly treated or
prevented, seems to be related to central serotonin deficiency and
hypercortisolaemia.
PMID- 10193122
TI - [Lactose intolerance in children. An analysis of hydrogen gas in exhaled air
simplifies and improves diagnosis].
PMID- 10193123
TI - [Restless legs. A much neglected syndrome].
AB - Ekbom's syndrome, or 'restless legs syndrome' (RLS), not only causes symptoms in
the extremities during waking hours, but also sleep disturbance and daytime
fatigue. Although the prevalence of RLS has been estimated to be 1-5%, the
condition is probably underdiagnosed and undertreated. Its onset may occur at any
age, and there may be long periods of remission, but the condition is generally
chronic. In its primary form, there is often a family history of the disorder
suggestive of an autosomal dominant mode of inheritance, where the results of EMG
(electromyography) and nerve conduction studies are normal. In secondary forms,
clinical signs and laboratory evidence of an associated abnormality are present.
The most characteristic symptom of RLS is the spontaneous occurrence of
paraesthesia or dysaesthesia during waking hours. The symptoms of RLS are worse
or exclusively present during rest, and are partially or temporarily relieved by
activity. About 80 per cent of RLS patients also suffer from 'periodic limb
movements during sleep' (PLMS), which may cause microarousals during sleep. The
diagnosis of RLS is based on characteristic clinical criteria, and the sleep
disturbance is diagnosed polysomnographically. L-dopa and clonazepam have been
found successful in the treatment of primary RLS, though lifelong treatment is
often necessary.
PMID- 10193124
TI - [Should nutritional support and fluid therapy be used in terminal care?
Guidelines for structured decision-making].
AB - A panel of experts within the European Association for Palliative Care (EAPC)
have drawn up guidelines as an aid to decision making concerning nutritional
support and fluid therapy in palliative cancer care. However, the issue is
characterised by a lack of scientifically based indications. The article consists
in discussion of the question of fluid therapy in terminal cases, in the light of
the EAPC guidelines. A meticulous assessment should be made of the patient in
terms of oncological and clinical status, symptomatology, prognosis, fluid and
nutritional status, nutrient and fluid intake, psychological attitudes, gastro
intestinal function, and the availability of technical expertise in enteral or
parenteral nutrition and fluid therapy. Case reports are used to illustrate the
importance of taking these factors into consideration, and of careful weighing of
the pros and cons.
PMID- 10193125
TI - [All rules have exceptions. Ectopic pregnancy in spite of negative HCG].
PMID- 10193126
TI - [Blood sampling during the neonatal period. Venipuncture is preferable to heel
puncture].
PMID- 10193127
TI - [Follow up of pediatric care is a good resource of knowledge that can be even
better].
PMID- 10193128
TI - [Nurses working with anticoagulants--a new subspecialty? Time for a new and
important kind of training].
PMID- 10193129
TI - ["Sudden deafness" has not been classified as a side-effect. No compensation from
the Drug Insurance Authority].
PMID- 10193130
TI - [Reduced mortality with mammographic screening. The natural course, too rough
methods resulted in miscalculation on breast cancer].
PMID- 10193132
TI - [Stem cells in the brain have been identified. Trials with human tissue will
confirm results from animal studies].
PMID- 10193133
TI - [Editor Richard Smith on targets for the British Medical Journal: to help
physicians practice medicine, to affect the international debate on health care].
PMID- 10193134
TI - Science, policy, and the future of substance abuse treatment in Rhode Island.
PMID- 10193135
TI - Absinthe makes the heart grow fonder.
PMID- 10193136
TI - The substance abuse treatment system in Rhode Island: an ecological view.
PMID- 10193137
TI - Enhancing alcohol treatment outcomes through aftercare and self-help groups.
PMID- 10193138
TI - Treatment considerations in the opioid dependent patient.
PMID- 10193139
TI - The physician's role in preventing alcohol and drug abuse.
PMID- 10193140
TI - The impaired practitioner: substance abuse and unprofessional conduct in Rhode
Island.
PMID- 10193141
TI - Physician Leadership on National Drug Policy: advocacy for an effective drug
policy.
AB - The founders of the PLNDP envisioned an active and committed group willing to
tackle the potentially controversial area of national drug policy. The group
already initiated a serious national debate about drug policy, inside and outside
of the medical profession. Several national professional societies moved beyond
their existing policies to embrace components of the PLNDP initiative. The group
meets again in the summer of 1999 to share goals and articulate the next steps in
research and advocacy. This meeting invites leaders in law, the enforcement
community, legislators, community coalition leaders, and experts in addiction
medicine and addiction psychiatry. PLNDP leaders expect that the subsequent
coalitions will affect the course of discussion about the nation's drug policy
far into the future.
PMID- 10193142
TI - Colorectal cancer screening and prevention.
PMID- 10193143
TI - Alcohol and drug use among Rhode Island high school students, 1997.
PMID- 10193144
TI - New guidelines for the prevention and treatment of osteoporosis. National
Osteoporosis Foundation.
PMID- 10193145
TI - Evaluation of the pressure transfer system in the intracranial cavity by
coherency.
AB - Coherency provides a method to evaluate model linearity. The characteristics of
pressure wave transmission in the intracranial cavity were studied by coherency
in 16 cats with hydrostatic pressure loading to assess the linearity of the
system, which is an assumption for use of the transfer function. Linearity was
observed in only the fundamental waves of the respiration-induced component and
the cardiac-induced component of intracranial pressure oscillation, and in the
second harmonic wave of the latter. Linearity at the other frequencies was close
to zero. The pressure transfer system in the intracranial cavity was basically a
non-linear system. As intracranial pressure rose, the increase in the pressure
transfer efficiency was largest in the low-frequency domain and smallest in the
high-frequency domain, indicating that the cerebral blood vessels are
characterized by inferior transmission of high frequency due to increased
intracranial pressure. In addition, the correlation between the coherencies of
the cardiac-induced fundamental wave component and intracranial pressure, and
between those of the cardiac-induced second harmonic wave component and
intracranial pressure, showed that the slope of the straight line was greater
between 45 and 70 mmHg than between 10 and 45 mmHg. This suggests that there is a
break point, located between 45 and 70 mmHg, where the increase in the coherency
values is accelerated, caused by an increase in the intracranial elastance, as
well as an increase in the cerebrovascular compliance due to the reduced vascular
transmural pressure.
PMID- 10193146
TI - Histological changes in the rat common carotid artery induced by aneurysmal
wrapping and coating materials.
AB - Histological changes in and around the arterial walls of rats were investigated
following topical application of aneurysmal wrapping and coating materials,
including a fibrin glue, a cyanoacrylate glue (Biobond), and cotton fibers
(Bemsheet). Bilateral common carotid arteries were exposed using sterile
techniques, and one of the test materials was applied to the right artery. The
left artery was used as the control. Changes in arterial histology were evaluated
at 2 weeks, 1 month, 2 months, and 3 months after surgery. The fibrin glue was
surrounded by intense inflammation at 2 weeks after surgery. Both the fibrin glue
and inflammation had disappeared at 2 months, but the glue had induced mild
inflammation in the adventitia. Biobond caused chronic inflammation, necrosis of
the media, and thickening of the arterial wall due to fibrosis in both the media
and adventitia. Bemsheet produced chronic inflammation, progressive fibrosis, and
granuloma. Connective tissue increased in the adventitia, but no major changes
were observed in the media. The Bemsheet fibers remained unchanged, and adhered
to the arterial wall. Although arterial stenoses were not observed in the present
study, the results suggest that cyanoacrylate glue can cause the arterial
occlusive lesions observed following aneurysm surgery.
PMID- 10193147
TI - Postoperative magnetic resonance imaging after acoustic neuroma surgery:
influence of packing materials in the drilled internal auditory canal on
assessment of residual tumor.
AB - Serial magnetic resonance (MR) images taken after acoustic neuroma surgery were
analyzed to evaluate the pattern and timing of postoperative contrast enhancement
in 22 patients who underwent acoustic neuroma removal via the suboccipital
transmeatal approach. The opened internal auditory canal (IAC) was covered with a
muscle piece in nine patients and with fibrin glue in 13. A total of 56 MR
imaging examinations were obtained between days 1 and 930 after surgery. MR
imaging showed linear enhancement at the IAC within the first 2 days after
surgery, and revealed nodular enhancement on day 3 or later in patients with a
muscle piece. MR imaging tended to show linear enhancement at the IAC,
irrespective of the timing of the examination in the patients with fibrin glue.
Postoperative MR imaging on day 3 or later showed the incidence of nodular
enhancement in patients with muscle was significantly higher than in patients
with fibrin glue. The results illustrate the difficulty in differentiating
nodular enhancement on a muscle piece from tumor by a single postoperative MR
imaging study. Therefore, fibrin glue is generally advocated as a packing
material of the IAC because it rarely shows masslike enhancement on postoperative
MR imaging. When a muscle piece is used in patients at high risk for
postoperative cerebrospinal fluid leaks, MR imaging should be obtained within the
first 2 days after surgery, since benign enhancement of muscle will not occur and
obscure the precise extent of tumor resection.
PMID- 10193148
TI - Transorbital-transpetrosal penetrating cerebellar injury--case report.
AB - A 4-year-old boy presented with a transorbital-transpetrosal penetrating head
injury after a butter knife had penetrated the left orbit. The knife tip reached
the posterior fossa after penetrating the petrous bone. Wide craniotomy and the
pterional, subtemporal, and lateral suboccipital approaches were performed for
safe removal of the object. The patient was discharged with left-sided blindness,
complete left ophthalmoplegia, and hypesthesia of the left face. Early
angiography is recommended to identify vascular injury which could result in
fatal intracranial hemorrhage.
PMID- 10193149
TI - Orthostatic hypotension improved after bilateral carotid endarterectomy--case
report.
AB - A 60-year-old male with recurrent syncopal attacks presented with orthostatic
hypotension on the head-up tilt test. Angiography also showed severe stenosis of
the bilateral extracranial carotid arteries. He underwent two-staged bilateral
carotid endarterectomy. After the operations, the orthostatic hypotension
resolved and the syncopal attacks have disappeared completely. Orthostatic
hypotension in this patient was due to vasodepressor-type carotid sinus syndrome
caused by compression of the carotid baroreceptors by atherosclerotic plaques.
PMID- 10193150
TI - Ruptured aneurysm of the orbitofrontal artery associated with dural arteriovenous
malformation in the anterior cranial fossa--case report.
AB - A 27-year-old male presented with a rare association of a ruptured orbitofrontal
artery aneurysm and a dural arteriovenous malformation (DAVM) fed by both
ethmoidal arteries, manifestation as severe headache, nausea, and vomiting.
Computed tomography revealed a hematoma within the right frontal lobe and diffuse
subarachnoid hemorrhage. The aneurysm was clipped successfully and the hematoma
was evacuated. After an uneventful postoperative course, the patient was referred
for gamma knife radiosurgery to treat the DAVM. In this case, the DAVM was
asymptomatic and pathogenetically unrelated to the aneurysm, which demanded
urgent treatment.
PMID- 10193151
TI - Intrameatal aneurysm successfully treated by meatal loop trapping--case report.
AB - A 77-year-old female presented with a rare intrameatal aneurysm manifesting as
sudden onset of headache, hearing loss, tinnitus, and vertigo associated with
subarachnoid hemorrhage. Meatal loop trapping was performed. After surgery, the
patient's functions recovered almost completely, probably because of the
preservation of the 7th and 8th cranial nerves and the presence of effective
collaterals in the area supplied by the anterior inferior cerebellar artery.
PMID- 10193152
TI - Pituitary metastasis from carcinoma of the urinary bladder mimicking pituitary
apoplexy--case report.
AB - A 70-year-old male presented with pituitary metastasis from transitional cell
carcinoma of the urinary bladder manifesting as sudden headache, transient
unconsciousness, and visual disturbance mimicking apoplexy of pituitary adenoma.
Computed tomography showed a suprasellar tumor with intratumoral and
intraventricular hemorrhage. Magnetic resonance imaging demonstrated an intra-
and suprasellar mass lesion mimicking pituitary adenoma. Diabetes insipidus
developed soon after. The tumor was subtotally removed. Histological examination
revealed transitional cell carcinoma. An intratumoral hemorrhage may be
associated with a pituitary metastasis if the patient presents with symptoms such
as pituitary apoplexy.
PMID- 10193153
TI - Paroxysmal kinesigenic choreoathetosis associated with frontotemporal arachnoid
cyst--case report.
AB - A 17-year-old male presented with paroxysmal kinesigenic choreoathetosis (PKC)
associated with frontotemporal arachnoid cyst. Xenon-133 single photon emission
computed tomography detected a slight but equivocal decrease in regional cerebral
blood flow in the vicinity of basal ganglia associated with the PKC episodes. PKC
continued after surgical removal of the cyst but was well controlled by oral
administration of carbamazepine. Whether the pathogenesis of symptomatic PKC was
associated with the cortical lesion could not be determined in the present case.
PMID- 10193154
TI - Probable lymphocytic hypophysitis diagnosed by short-term serial computed
tomography and gallium-67 scintigraphy--case report.
AB - A 61-year-old female presented with headache, malaise, and left oculomotor nerve
paralysis. Computed tomography (CT) demonstrated a diffuse pituitary mass and
enlarged pituitary stalk with homogeneous contrast enhancement. Her symptoms
gradually resolved without treatment. Gallium-67 scintigraphy showed abnormal
uptake in the pituitary lesion. Serial CT every 2 weeks after admission showed
homogeneous contrast enhancement and shrinking of the pituitary mass to a normal
size 12 weeks after the onset. The final diagnosis was lymphocytic
adenohypophysitis without biopsy. Recurrence has not been observed for 8 years
after discharge. The patient did not need hormone replacement therapy.
Histological examination is not always necessary to diagnose probable lymphocytic
adenohypophysitis with the characteristic feature of rapid onset, abnormal
gallium-67 uptake in the lesion, and resolution of symptoms in the acute stage
with shrinking of the lesion on neuroimaging.
PMID- 10193155
TI - [The jet lag syndrome].
PMID- 10193156
TI - [The pharmacotherapy of arterial hypertension and the prevention of
cardiovascular events. From evidence-based medicine to the new therapeutic
opportunities].
PMID- 10193157
TI - [The video recording of medical visits for the study of physician-patient rapport
in general medicine. An experimental experience in Italy].
AB - The communication and relationship between doctors and patients has been given
increased attention in recent years. There are many different methods by which to
collect data on doctor-patient communication and relationship: of these,
videorecording seems to have the most advantages. The objective of this article
is to describe the method we used to make videorecorded consultations in General
Medical Practice in Italy. In particular, the article addresses: 1) the technical
feasibility of videorecording consultations; 2) a possible answer to the problem
of informed consent both from doctors and from patients. At present, the archives
collect 258 videotaped consultations of 14 General Practitioners: about three
patients in four (75.9%) did consent to have their consultation recorded; a high
range of videorecorded consultations (94.2%) does not present technical problems.
In line with published surveys, these recording consultations are an increasingly
important method of studying communication and doctor-patient relationship, and
of teaching/learning these aspects of medical practice.
PMID- 10193158
TI - [The clinical and echographic assessment of thyroid function and structure in
patients with a chronic inflammatory intestinal disease].
AB - In Crohn's disease (CD) and in ulcerative colitis (UC) data about possible
thyroid involvement are lacking. We studied thyroid morphology and function in 41
patients affected by active inflammatory bowel disease (IBD) (14 UC; 27 CD)
before (all) and 45 and 90 days after onset of therapy (23/41), and in 60 normal
control subjects. At each time, the following tests were performed: thyroid
sonography, hormonal and immunological assays. A statistically significant
increase of thyroid volume was found in IBD compared to control subjects, more
frequently in CD (70.4%) than in UC (14.3%). Parenchymal structure was
inhomogeneous (88.4% CD; 15.4% UC) with increased frequency compared to control
subjects (12.7%). Hormone assays demonstrated increased FT4 values in UC (64.3%)
and decreased T4 values in CD (51.8%). Patients affected with IBD showed an
increased frequency of anti-thyroglobulin and anti-thyroid peroxidase antibodies.
Such abnormalities subsided only partially after therapy. Our data suggest that
in IBD there is a frequent thyroid involvement with morphological, hormonal, and
immunological abnormalities.
PMID- 10193160
TI - [12 months to 2000].
PMID- 10193159
TI - [Extranodal lymphomas. A rare clinical entity or a protean disease? A case
report].
AB - Aim of the present study is to describe a case of extranodal lymphoma localized
in paravertebral site, near to thoracic spine. The clinical onset of the
affection was as a radicular sciatalgic pain, resistant to long-term current
therapy by NSAIDs, and determined by neuroradicular involvement by the neoplastic
bulk. The interest of the present case is determined by: 1) the presence of a
pain which, for a long while, mimicked one of the most trivial painful syndromes;
2) the fact that extranodal lymphomas are not so rare ones. An extensive research
of such entities is therefore mandatory; 3) the diagnosis was made by means of
non-invasive examination, and needle biopsy was performed only to confirm a
picture which was already patent.
PMID- 10193161
TI - [Diabetes and dyslipidemia].
PMID- 10193162
TI - [The therapy of hepatocarcinoma].
PMID- 10193163
TI - [Tumor angiogenesis].
AB - The formation of new vessels, (angiogenesis) characterizes body development and
is pivotal in some diseases. In particular, angiogenesis is crucial for the
growth of tumors and metastasis diffusion. The beginning of tumor angiogenesis is
caused by the selection of a cancer cell clone which induces an unbalance between
inducers and inhibitors of angiogenesis. The inhibition of this process by
natural or chemical compounds increases apoptotic index in the tumors, does not
causes drug resistance and has been demonstrated to induce cancer dormancy in
many animal models.
PMID- 10193164
TI - [Celiac disease. Recent findings on its pathogenesis, diagnosis and clinical
presentation].
AB - Coeliac disease is a gluten-sensitive enteropathy which results in a permanent
malabsorption of nutrients in that portion of the small intestine (the jejunum)
that is damaged. A genetic, inheritable disease, it is directly related to
ingestion of certain wheat proteins especially found in rye secalins, barley
hordeins and, in a much lower amount, oat avenins. A fundamental role in the
pathological response is played by grain prolamins (gliadins). The actual damage
to intestinal mucosa is almost certainly mediated by the immune system but its
mechanism has not been so far clarified. Coeliac disease incidence rate is ever
increasing among children and adolescents and it is rather frequently reported as
relapsing in the third and fourth decade. The most distressing problems of
malabsorption syndrome are diarrhea, weight loss, meteorism, abdominal pain,
vomiting and asthenia; nonetheless, not all patients report symptoms. Both
diagnosis and differential diagnosis--intestinal lymphoma, refractory sprue-
prove difficult: a diagnosis of gluten intolerance can be made through careful
consideration of a series of laboratory findings which are being improved by
researchers in order to avoid delays for patients with probable gluten-sensitive
enteropathy with non-specific symptoms. Although there may be many clinical signs
and laboratory tests indicating probable malabsorption, the likely gold standard
of diagnosing coeliac disease remains to be the jejunal biopsy.
PMID- 10193165
TI - [The prevention of type-2 diabetes and its complications].
PMID- 10193166
TI - [The chronic reduction of tissue perfusion and neoplasm promotion].
PMID- 10193167
TI - [The National Heart Transplant Registry. The 9th Official Report (1984-1997). The
Spanish Heart Transplant Groups. The Section of Heart Transplantation of the
Spanish Society of Cardiology].
AB - The results of the Spanish National Registry of Heart Transplantation, made up of
12 centers currently performing transplantation are reported. 318
transplantations performed in 1997, which, together with those performed since
1984, totals 2, 406 transplantations. The number of procedures increased again
last year, breaking the trend of recent years. This has probably been due to an
increase in organ obtention and a reduction in the acceptance level required,
necessary because the waiting list has increased. Over 100 variables have been
analyzed per patient to measure mortality predictors. The results are comparable
to those published by the International Society of Heart and Lung
Transplantation. Early survival, at the first 30 days post-transplantation, is
lower in the National Registry, though 1-year survival tends to be higher, with a
3% fall in the National Registry and 4% in the International one. In conclusion,
heart transplantation is a procedure completely established in Spain, with
results comparable to those of the International Registry, due to the great
experience of the centers.
PMID- 10193168
TI - [Radiofrequency ablation of ventricular tachycardia in patients with ischemic
cardiopathy].
AB - PURPOSE: We analyze the efficacy of radiofrequency catheter ablation and the
clinical significance of inducible ventricular tachycardia that had never been
documented before (non clinical ventricular tachycardia) in patients with
ventricular tachycardia and coronary artery disease. METHODS: Thirty-four
patients (30 men, aged 61 +/- 10 years, left ventricular ejection fraction 31 +/-
10%) with coronary artery disease and documented clinical ventricular tachycardia
underwent radiofrequency ablation. Thirty-four clinical ventricular tachycardia
and 11 non clinical ventricular tachycardia were treated with radiofrequency.
Initial therapeutic success was considered when none of the ventricular
tachycardia treated with radiofrequency could no longer be induced at the last
stimulation protocol before discharge. RESULTS: Clinical ventricular tachycardia
was successfully ablated in 23 patients (68%). Initial therapeutic success was
obtained in 21 patients (62%). In 6 of them, 7 non clinical ventricular
tachycardia poor tolerated were also induced. During a mean follow-up of 26 +/-
15 months ventricular tachycardia recurred in 6 patients (29%). Five of the 6
patients who recurred were discharged with no inducible non clinical ventricular
tachycardia. Three patients died during the follow-up. Two of them from heart
failure (one with previous recurrence) and the other suddenly with documented
asystole after loss of consciousness without previous recurrence. CONCLUSIONS: In
our series of patients with ventricular tachycardia and coronary artery disease
selected for radiofrequency ablation, acute success was obtained in 62%. After a
mean follow-up of 2 years, 44% of all the patients were free from ventricular
tachycardia. Although the possibility of ventricular tachycardia recurrence is
high (29%), the recurrence rate is not increased by the inducibility of non
clinical ventricular tachycardia.
PMID- 10193169
TI - [The ablation of ventricular tachycardias postinfarct: the search for tools and
candidates].
PMID- 10193170
TI - [Ductus closure in adults with the Rashkind device: comparative results].
AB - INTRODUCTION: Catheter occlusion of the persistent ductus arteriosus with
Rashkind device is an alternative to the surgical closure demonstrated in
children, however a few results have been reported of occlusion in adults.
METHOD: From 1990 to 1996 in 127 patients with persistent ductus arteriosus
undergoing occlusion by Raskind device. Two groups according age: 105 children (<
14 years) and 22 adults (> 14 years), were studied retrospectively. The results
were analysed by immediate aortogram and follow-up at 24 hours, 6 and 12 months
by color-Doppler echocardiograms. RESULTS: The adults were frequently
asymptomatic (86%) and with high incidence (59%) of silent ductus. Similar QP/QS
(1.61 +/- 0.47 in adults vs 1.49 +/- 0.51) was calculated although pulmonary
pressure was superior in children (12.50 +/- 2.97 vs 16.84 +/- 5.88 mmHg; p =
0.003). In group > 14 years the ductal anatomy favorable (Krichenko type A or B)
was more frequent (91% vs 73%; p = 0.06) and ductal diameter significantly higher
(3.03 +/- 1.50 vs 2.41 +/- 0.96 mm; p = 0.009). In adults 17 mm umbrella were
used more frequently (91 vs 61%; p = 0.02). Absence complications (embolization,
bacteremia, haemolysis, proximal stenosis of the left pulmonary artery) were
found in adults against 4.72% in children. The occlusion were more effective in
adults specially in early controls: 55% vs 34% (p = 0.09), 82% vs 69%, 91% vs 77%
and 95% vs 83% (p > 0.10). Multivariate analysis identified age as an independent
predictor of complete occlusion. CONCLUSION: Our experience in transcatheter
occlusion of persistent ductus arteriosus with Rashkind device in adults support
the efficacy, safety and excellent early results despite higher incidence of
silent asymptomatic ductus.
PMID- 10193171
TI - [The clinical and angiographic evolution of dilated lesions in the proximal
segment of the anterior descending coronary artery: stent versus balloon].
AB - INTRODUCTION AND OBJECTIVES: The restenosis rate after coronary balloon
angioplasty of lesions located in the proximal segment of the left anterior
descending coronary artery is high, having been recommended elective stent
implantation in order to improve the outcomes. The aim of this study was to
analyze clinical, anatomic and angiographic factors related to the short-term
outcome after angioplasty of severe lesions in the proximal segment of the left
anterior descending artery, with and without stent implantation. MATERIAL AND
METHODS: We study 87 patients with severe stenosis (> or = 70%) of the proximal
segment of left anterior descending artery treated successfully with angioplasty.
In 54 patients (62%) a conventional balloon was used (group A) and in 33 (38%) a
stent was implanted (group B). RESULTS: Mean age of patients was 61.9 +/- 12
years old, 74% were male and angioplasty was performed because of unstable angina
in 72%. At the end of the follow-up (mean 6.3 +/- 1.5 months), 21% of patients in
group B had angina vs 54% in group A (p = 0.03). Group B patients experienced a
lower restenosis rate (30% vs. 50%; p = 0.07) and less repeat angioplasty
procedures (33% vs 21%; p = NS) than group A. These results were maintained
independently of the vessel diameter (< 3 mm or > or = 3 mm) or when an optimal
result (< 25%) after balloon angioplasty was obtained. CONCLUSIONS: In our
experience, stenting of lesions located in the proximal segment of the left
anterior descending artery appears imply a better short-term clinical,
angiographic outcome and a lower restenosis rate than lesions treated with
conventional balloon angioplasty, even despite an optimal result after balloon
angioplasty or independently of the vessel diameter. Future studies will be
necessary to confirm these results.
PMID- 10193172
TI - [The tilt-table test in assessing syncope of unknown origin: do differences exist
between children and adults?].
AB - BACKGROUND AND OBJECTIVES: Little is known about the differences between children
and adults in the results of head-up tilt test. This study sought to investigate
the potential differences concerning: a) the clinical profile and circumstances
of spontaneous syncope; b) the overall diagnostic performance of the test, and c)
the type of positive response obtained. MATERIAL AND METHODS: We studied 31
children and 123 adults with unexplained syncope. If baseline test (tilting at 70
degrees for 30 min) resulted negative, it was repeated under isoprenaline low
dose infusion. RESULTS: There were no differences in either clinical profile,
except for severe traumatism more frequent in adults (25% vs. 3% in children; p <
0.05), or overall diagnostic performance (39% in children vs. 33% in adults; p =
NS). However, the way the test rendered positive (via basal tilting in 92% of
children vs. 50% in adults; p < 0.05) and the rate of cardioinhibitory response
(42% in children vs 8% in adults; p < 0.01) were significantly different.
CONCLUSIONS: In this study children, in contrast to adults, rarely have a
positive response in tilting under isoprenaline infusion. They also present a
much higher rate of cardio-inhibitory response than adults.
PMID- 10193173
TI - [Cor triatriatum].
PMID- 10193174
TI - [Constrictive pericarditis and Behcet's disease: a very rare association].
AB - Although benign acute pericarditis can be considered a common cardiac
complication of Behcet's disease, the association of this systemic vasculitis
with constrictive pericarditis has not been described. A case of this peculiar
clinical association is presented, and some interesting diagnostic points are
discussed.
PMID- 10193175
TI - [The use of oral amiodarone as a chronic treatment in a patient with prior
fulminant hepatitis due to intravenous amiodarone].
AB - Acute hepatitis for intravenous amiodarone is an uncommon problem with scarce
appearances in medical literature. Sometimes, it has postulated that the vehicle
of the intravenous preparation and not the active principle is the possible cause
of this complication. We report a patient with fulminating hepatitis and severe
encephalopathy following the administration of intravenous amiodarone. We present
also the clinical evolution of the patient after reintroduction of oral
amiodarone. In the end, we make a review of the associated literature with our
case.
PMID- 10193176
TI - [Cardiovascular changes in the cutis laxa congenita syndrome].
AB - Cutis laxa is a unusual disorder of the connective tissue. It may be hereditary
or acquired and from the genetical viewpoint, can be either of the dominant or of
the recessive type. The autosomic dominant type, less frequent, has a late
beginning and the evolution is usually benign, and it seldom has cardiovascular
anomalies. On the contrary, the recessive type usually has an early beginning
having frequent cardiovascular anomalies, with the outcome of death early in
infancy. We report two siblings with the recessive type of the illness, having
peripheral arterial stenosis of pulmonary branches. We review the literature with
special attention to the angiohemodynamic findings, as there are few
bibliographic reports about this subject, as well as about the different
hypothesis on the pathogenesis of this illness.
PMID- 10193177
TI - [Atrial fibrillation and the Wolff-Parkinson_White syndrome in a 68-year-old
patient with tuberous sclerosis].
AB - Tuberous sclerosis is an autosomal-dominant disease with involvement of several
organs, the heart included. The cardiac anomaly most frequently found is the
rhabdomyoma association. However, WPW association has also been encountered more
common than usual. In the majority of the published related-series, infant or
adolescent patients are described. We report the case of a 68-year-old patient
with tuberous sclerosis whose first cardiac manifestation was a pre-excited
atrial fibrillation. This association is reviewed and the consideration of
accessory pathways is highlighted as the first mechanism to take into account
when arrhythmias are present in these patients even in adult age.
PMID- 10193178
TI - [The imaging diagnosis of pericardial agenesis].
AB - Pericardial agenesis is a rare anomaly, difficult to diagnose. Its evolution is
usually benign. However, on rare occasions, partial defects have been the cause
of sudden death. Therefore, surgical treatment has sometimes been indicated, even
though in the cases were asymptomatic. We report the case of a 50 year-old woman
with partial pericardial agenesis and herniation of left atrial appendage trough.
The defect was discovered by a routine chest x-ray and treated in a conservative
way. Current diagnostic and therapeutic techniques are reviewed.
PMID- 10193179
TI - [The usefulness of thrombolysis units in the treatment of acute myocardial
infarct].
PMID- 10193180
TI - [Ready-made crowns in the deciduous dentition].
AB - The following review of the literature on "prefabricated crowns for deciduous
teeth" attempts to highlight the benefits and limitations of this treatment
modality. The use of prefabricated crowns is indicated in the following
situations: severe destruction of the clinical crown, deep approximal cavities,
bilateral approximal cavities, circumferential caries, history of root canal
treatment, and need for fixed space retention. Compared to amalgam restorations
involving two or more surfaces, prefabricated crowns on deciduous molar teeth
gave very high survival rates. They consist of a chromium-nickel-steel alloy and
are reported to have an acceptable gingival tolerance profile. In contrast to the
Anglo-American countries this treatment modality is quite uncommon in Germany. A
probable reason for this reservation could be that many clinicians often fail to
see the need for a filling in the deciduous dentition. Besides, many dentists are
reluctant to use local anesthesia in children, which is inevitable in preparing
and fitting a prefabricated crown. In the United States and UK dentists are less
frequently confronted with this problem, as complex treatments are often carried
out under nitrous oxide sedation or insufflation anesthesia. Modern filling
materials have been introduced which have the potential to narrow the indications
for prefabricated stainless steel crowns. Against this background, future studies
are necessary to compare the survival rates of prefabricated crowns and modern
filling materials.
PMID- 10193181
TI - [Oscillating procedures in the preparation technic (II). Their development and
application possibilities].
AB - The acceptance and use of amalgam as an everyday filling material is decreasing.
Today, direct composite fillings are widely used to restore even extensive
lesions in premolars and molars. The sonoabrasive method presented here uses
special working tip geometries (SONSICSYS approx) to a allow a "finishing
preparation" of standardized interproximal cavities. In this process, the
"negative shape" of the working tip is transferred to the tooth. It is now
possible, for the first time, to accurately restore class II box cavities using
prefabricated ceramic inlays. Complicated layering techniques are no longer
necessary and there is no risk of compromising interproximal contacts remaining
occlusal defects can be restored with conventional composites. The use of special
SONICSYS working tips for ceramic and cast gold cavity preparations ensures
precise cavity geometries with "close-to-perfect" margins. The sonoabrasive
method greatly lowers the technique sensitivity of such difficult types of
preparations.
PMID- 10193182
TI - Saving zebrafish mutants.
AB - At present, the zebrafish Danio rerio is the only vertebrate species for which a
large-scale mutagenesis effort to identify developmental genes has been reported.
Several laboratories are now intensely pursuing the molecular characterization of
the genes affected by these mutations. One important criterion for the identity
of the mutated gene is the rescue of the mutant phenotype by a wild-type (wt)
copy of the gene. Until recently, most rescue attempts were carried out by
injecting wt messenger RNA (mRNA) into fertilized eggs. A report by Yan and
collaborators shows the partial rescue of floatinghead mutants by injection of
genomic fragments cloned in either bacterial artificial chromosomes or
bacteriophage lambda vectors. Combined with other ongoing efforts to characterize
the zebrafish genome, this approach of mutant rescue opens interesting avenues
for a systematic functional analysis of vertebrate genes.
PMID- 10193183
TI - Mosaic bacterial chromosomes: a challenge en route to a tree of genomes.
AB - In a recent analysis J.G. Lawrence and H. Ochman [Proc Natl Acad Sci USA
1998;95:9413-9417 (Reference 1)] surmised that about 10% of the current E. coli
genome consists of genes that were acquired in over 200 events of lateral gene
transfer, which occurred subsequent to the divergence of E. coli and Salmonella
some 100 million years ago. Overall, the data suggest that no less than 18% of E.
coli's genes might be relatively recent foreign acquisitions, and that the
average rate of acquisition may be close to about 16 kb per million years. These
quantitative estimates of comparatively recent genome flux have profound impact
on evolutionary genome comparisons. They tend to suggest that a search should be
on to identify principles that might ultimately govern gene distribution patterns
across prokaryotic genomes.
PMID- 10193184
TI - The year of the worm.
AB - Developmental biology has almost come full circle. Initially aimed at description
at the organismal level, in the last 25 years it has zoomed in on individual
genes that are involved in specific steps in development. Now, complete genome
sequences are becoming available--and to gain a full understanding of the
relevance of the complete genome, experimental developmental biology will hold
centre stage again, but now armed with large genome databases, and with a new set
of refined genetic tools. The first multicellular organism to be sequenced is the
nematode C. elegans. This review aims to recognise some new avenues in C. elegans
experimental biology that are opened by the genome sequence.
PMID- 10193185
TI - Clearing a path through the jungle: progress in Arabidopsis genomics.
AB - Progress in sequencing the genome of the model plant Arabidopsis is reviewed. The
resulting analysis of the sequence indicates an information-rich genome that is
being tackled by a variety of high-throughput approaches aimed at understanding
the functions of plant genes. The information derived from these systematic
studies is providing important new knowledge of biological processes found
uniquely in plants for comparison with that obtained in other multicellular
organisms.
PMID- 10193186
TI - Comparative genomics: the key to understanding the Human Genome Project.
AB - The sequencing of the human genome is well underway. Technology has advanced,
such that the total genomic sequence is possible, along with an extensive
catalogue of genes via comprehensive cDNA libraries. With the recent completion
of the Saccharomyces cerevisiae sequencing project and the imminent completion of
that of Caenorhabditis elegans, the most frequently asked question is how much
can sequence data alone tell us? The answer is that that a DNA sequence taken in
isolation from a single organism reveals very little. The vast majority of DNA in
most organisms is noncoding. Protein coding sequences or genes cannot function as
isolated units without interaction with noncoding DNA and neighboring genes. This
genomic environment is specific to each organism. In order to understand this we
need to look at similar genes in different organisms, to determine how function
and position has changed over the course of evolution. By understanding
evolutionary processes we can gain a greater insight into what makes a gene and
the wider processes of genetics and inheritance. Comparative genomics (with model
organisms), once the poor relation of the human genome project, is starting to
provide the key to unlock the DNA code.
PMID- 10193187
TI - Genomics and the biology of parasites.
AB - Despite the advances of modern medicine, the threat of chronic illness,
disfigurement, or death that can result from parasitic infection still affects
the majority of the world population, retarding economic development. For most
parasitic diseases, current therapeutics often leave much to be desired in terms
of administration regime, toxicity, or effectiveness and potential vaccines are a
long way from market. Our best prospects for identifying new targets for drug,
vaccine, and diagnostics development and for dissecting the biological basis of
drug resistance, antigenic diversity, infectivity and pathology lie in parasite
genome analysis, and international mapping and gene discovery initiatives are
under way for a variety of protozoan and helminth parasites. These are far from
ideal experimental organisms, and the influence of biological and genomic
characteristics on experimental approaches is discussed, progress is reviewed and
future prospects are examined.
PMID- 10193188
TI - The impact of genomics on mammalian neurobiology.
AB - The benefit of genomics lies in the speeding up of research efforts in other
fields of biology, including neurobiology. Through accelerated progress in
positional cloning and genetic mapping, genomics has forced us to confront at a
much faster pace the difficult problem of defining gene function. Elucidation of
the function of identified disease genes and other genes expressed in the Central
nervous system has to await conceptual developments in other fields.
PMID- 10193189
TI - From genome to aetiology in a multifactorial disease, type 1 diabetes.
AB - The common autoimmune disease type 1 diabetes provides a paradigm for the genetic
analysis of multifactorial disease. Disease occurrence is attributable to the
interaction with the environment of alleles at many loci interspersed throughout
the genome. Their mapping and identification is difficult because the disease
associated alleles occur almost as commonly in patients as in healthy
individuals; even the highest-risk genotypes bestow only modest risks of disease.
The identification of common quantitative trait loci (QTL) in autoimmune disease
and in other common disorders, therefore, requires a very close marriage of
genetics and biology. Two QTLs have been identified in human type 1 diabetes: the
major histocompatibility complex HLA class II loci and a promoter polymorphism of
the insulin gene. The evidence for their primary roles in disease aetiology
demonstrates the necessity of combined studies of genetics and biology. Their
functions and interaction underpin an emerging picture of the basic causes of the
disease and direct analyses towards other candidate genes and pathways. The
genetic tools used for QTL identification include transgenesis and gene
knockouts, whole genome scanning for linkage, mouse congenic strains, linkage
disequilibrium mapping, and the establishment of ancestral haplotypes among
disease-associated chromosomes.
PMID- 10193190
TI - The legacies of Langmuir, Ising, and Pauling: ligand binding and the helix-coil
transition.
AB - Multiple, independent sites or domains behave, on chemical change, in a manner
predicted by Langmuir. Distortions of this behavior have been attributed to
interactions between the domains, which vary with the progress of the changes
occurring at the sites or domains. The two main models for nearest neighbor
interactions perturbing the Langmuir prediction for independent domains are those
of Ising and Pauling. If we designate the initial site as (-) and the changed
site as (+), then the Langmuir requirement for independence of sites yields a set
of nearest neighbor interactions such that the (- -), (- +), (+ -), and (+ +)
interactions are all identical. This identity is usually characterized as "no
interactions." Ising, in dealing with electron pairs, invoked nearest neighbor
interactions such that the interactions of the (- -) paris equaled those of the
(+ +) pairs, but with the (- +) and (+ -) pairs differing from the reference (-
) pair. Pauling, on the other hand, postulated that only the (- -) and (+ -)
pairs interacted differently. A dichotomy has arisen in the application of these
two models, with some investigators ignoring or overlooking one of the models. We
explore these models, alone and combined, with exact partition functions
generated in reasonable computer times for hundreds of sites employing our
combinatorial algorithm.
PMID- 10193191
TI - Equilibrium unfolding CD studies of bovine beta-lactoglobulin and its 14-52
fragment at acidic pH.
AB - Bovine beta-lactoglobulin represents an interesting example of context-dependent
secondary structure induction. In fact, secondary structure predictions indicated
that this beta-barrel protein has a surprisingly high alpha-helical preference,
which was retained for short fragments. Cooperative transitions from the native
beta-sheet to alpha-helical structures were additionally induced by organic
solvents, in particular trifluoroethanol. As a result of this high alpha-helical
preference, it has been proposed that non-native alpha-helical intermediates
could be formed in the unfolding pathway of this protein. In order to provide a
better understanding of the processes that underlie conformational plasticity in
this protein, CD measurements in the presence of increasing amounts of urea and
in the presence of organic solvents were performed. Urea unfolding studies,
performed at pH 2.1 and 37 degrees C, revealed an apparent two-state transition,
and afforded no evidence of non native alpha-helical intermediates. The protein
treated with up to 6M urea, refolded to the native structure, while treatment
with higher molar concentration urea, lead to partial misfolding. A 29-mer
peptide covering the region of strands a and b of the intact protein,
characterized by the presence of 4/3 heptad repeats, was synthesized and studied
by CD in the presence of different solvents. On the basis of the obtained
results, a mechanism was proposed to explain the structural transition from the
beta to alpha structure, provoked by organic solvents in the intact protein.
PMID- 10193192
TI - 1-anilino-8-naphthalene sulfonate as a protein conformational tightening agent.
AB - 1-Anilino-8-naphthalene sulfonate (ANS) anion is conventionally considered to
bind to preexisting hydrophobic (nonpolar) surfaces of proteins, primarily
through its nonpolar anilino-naphthalene group. Such binding is followed by an
increase in ANS fluorescence intensity, similar to that occurring when ANS is
dissolved in organic solvents. It is generally assumed that neither the negative
sulfonate charge on the ANS, nor charges on the protein, participate
significantly in ANS-protein interaction. However, titration calorimetry has
demonstrated that most ANS binding to a number of proteins occurs through
electrostatic forces, in which ion pairs are formed between ANS sulfonate groups
and cationic groups on the proteins (D. Matulis and R. E. Lovrien, Biophys. J.,
1998, Vol. 74, pp. 1-8). Here we show by viscometry and diffusion coefficient
measurements that bovine serum albumin and gamma-globulin, starting from their
acid-expanded, most hydrated conformations, undergo extensive molecular
compaction upon ANS binding. As the cationic protein binds negatively charged ANS
anion it also takes up positively charged protons from water to compensate the
effect of the negative charge, and leaves the free hydroxide anions in solution
thus shifting pH upward (the Scatchard-Black effect). These results indicate that
ANS is not always a definitive reporter of protein molecular conformation that
existed before ANS binding. Instead, ANS reports on a conformationally tightened
state produced by the interplay of ionic and hydrophobic characters of both
protein and ligand.
PMID- 10193193
TI - Conformational change of ascidiacyclamide caused by asymmetric modification for
an isoleucine residue: structural analyses of [Gly], [Leu], and
[Phe]ascidiacyclamides by x-ray diffraction and NMR spectroscopy.
AB - Ascidiacyclamide, a cytotoxic cyclic peptide from tunicate, is composed of
unusual amino acids and has a repeated sequence, c[-thiazole-D-Val-oxazoline-L
Ile-]2 ([Ile]ASC). The symmetric chemical structure has been assumed to be
correlated with the cytotoxicity, and it is reasonable to consider that the
disturbance of its structure from the C2 symmetry results in the changes of
conformation and activity. In order to quantitatively estimate the molecular
conformation-activity relationship, an isoleucine residue was substituted by Gly,
Leu, or Phe to disturb the C2 symmetry. The conformations of three derivatives
were examined by nmr spectroscopy and the crystal structure of [Leu]ASC was also
analyzed by x-ray diffraction method. The 1H-nmr experiments and the constrained
molecular dynamics simulations showed the twisted "figure 8" conformers for [Gly]
and [Phe]ASCs and the "square" conformer for [Leu]ASC in the DMSO solution. The x
ray crystal analysis of [Leu]ASC also revealed the square form similar to the
solution structure. On the other hand, their cytotoxic activities were measured
using L1210 leukemia cells and were related with the bulkiness and/or
hydrophobicity of the side chain of the substituted amino acid; [Phe] > or =
[Ile] > [Leu] >> [Gly]ASCs. As an attempt to consider the correlation between the
activity and conformer, the accessible surface area (ASA) was calculated for each
derivative to estimate the size or bulkiness of its conformation. Although the
ASAs of nmr structures were not directly related to the type of conformer (figure
8 or square form), it was an important probe to consider the cytotoxicity of each
derivative.
PMID- 10193194
TI - Nonideality and protein thermal denaturation.
AB - We studied the thermal denaturation of eglin c by using CD spectropolarimetry and
differential scanning calorimetry (DSC). At low protein concentrations,
denaturation is consistent with the classical two-state model. At concentrations
greater than several hundred microM, however, the calorimetric enthalpy and the
midpoint transition temperature increase with increasing protein concentration.
These observations suggested the presence of intermediates and/or native state
aggregation. However, the transitions are symmetric, suggesting that
intermediates are absent, the DSC data do not fit models that include
aggregation, and analytical ultracentrifugation (AUC) data show that native eglin
c is monomeric. Instead, the AUC data show that eglin c solutions are nonideal.
Analysis of the AUC data gives a second virial coefficient that is close to
values calculated from theory and the DSC data are consistent with the behavior
expected for nonideal solutions. We conclude that the concentration dependence is
caused by differential nonideality of the native and denatured states. The
nondeality arises from the high charge of the protein at acid pH and is
exacerbated by low buffer concentrations. Our conclusion may explain differences
between van't Hoff and calorimetric denaturation enthalpies observed for other
proteins whose behavior is otherwise consistent with the classical two-state
model.
PMID- 10193195
TI - Protein loops on structurally similar scaffolds: database and conformational
analysis.
AB - A general problem in comparative modeling and protein design is the
conformational evaluation of loops with a certain sequence in specific
environmental protein frameworks. Loops of different sequences and structures on
similar scaffolds are common in the Protein Data Bank (PDB). In order to explore
both structural and sequential diversity of them, a data base of loops connecting
similar secondary structure fragments is constructed by searching the data base
of families of structurally similar proteins and PDB. A total of 84 loop families
having 2-13 residues are found among the well-determined structures of resolution
better than 2.5 A. Eight alpha-alpha, 20 alpha-beta, 19 beta-alpha, and 37 beta
beta families are identified. Every family contains more than 5 loop motifs. In
each family, no loops share same sequence and all the frameworks are well
superimposed. Forty-three new loop classes are distinguished in the data base.
The structural variability of loops in homologous proteins are examined and shown
in 44 families. Motif families are characterized with geometric parameters and
sequence patterns. The conformations of loops in each family are clustered into
subfamilies using average linkage cluster analysis method. Information such as
geometric properties, sequence profile, sequential and structural variability in
loop, structural alignment parameters, sequence similarities, and clustering
results are provided. Correlations between the conformation of loops and loop
sequence, motif sequence, and global sequence of PDB chain are examined in order
to find how loop structures depend on their sequences and how they are affected
by the local and global environment. Strong correlations (R > 0.75) are only
found in 24 families. The best R value is 0.98. The data base is available
through the Internet.
PMID- 10193196
TI - Stereochemical specificity of Alzheimer's disease beta-peptide assembly.
AB - The formation and growth of insoluble amyloid deposits composed primarily of the
human beta-amyloid peptide (A beta) in brain is an essentially invariant feature
of Alzheimer's disease (AD) and is widely believed to contribute to the
progressive neurodegeneration of the disorder. To probe the specificity of
amyloid formation and growth, we synthesized and examined the self-assembly of D-
and L-stereoisomers of A beta in vitro. While both enantiomers formed insoluble
aggregates at similar rates with amyloid-like fibrillar morphology, deposition of
soluble A beta peptide onto preexisting A beta aggregates was stereospecific.
Although the L-peptide deposited readily onto immobilized L-A beta aggregates
with first-order kinetic dependence on soluble peptide concentration, essentially
no association between the D-peptide and L-template was observed. Similarly, the
D-peptide deposited with first-order kinetics onto a D-A beta aggregate template
but did not deposit onto a similar template composed of aggregates of the L
enantiomer. Furthermore, although the L-A beta isomer deposited onto authentic AD
amyloid in preparations of unfixed AD brain, no focal association between the D
peptide and brain amyloid was detected. These results establish that deposition
of soluble A beta onto preexisting amyloid template is stereospecific, likely
involving direct docking interactions between peptide backbone and/or side chains
rather than simple hydrophobic association.
PMID- 10193197
TI - Receptor binding activities of Schefflera triterpenoids and oligosaccharides.
AB - Roots and leaves of Schefflera bodinieri were studied for their activity in the
central nervous system (CNS) by bioassay-guided isolation in conjunction with
receptor binding assays. As demonstrated in preliminary screening, ethanol
extracts of leaves and roots of S. bodinieri showed strong binding affinity to a
number of CNS receptors. Chemical investigation of this plant species was then
conducted and fourteen plant ingredients were obtained. In this study, nine of
these isolated compounds were tested by fifteen receptor binding assays for their
CNS activities. Results showed that three compounds, namely bodinone, bodinone
glycoside and D-sorbitol, were able to selectively bind to muscarine receptors, a
trisaccharide bound to Ca2+ channel and 5HT-2 receptors, stigmasterol 3-O
glucoside bound to 5HT-2 receptors, and bodirin A bound to dopamine-2 receptors
with IC50 values at microM level. In the drug-interaction studies, bodinone,
bodinone glycoside, bodirin A, bodinitin A and the trisaccharide were found to
affect binding affinity of certain specific binding agents to the 5HT1C, 5HT2,
opiate, beta-adrenergic and histamine 1 receptors. These observations suggest
interactions between the plant ingredients and receptors as well as synergistic
effect of various compounds at receptor level.
PMID- 10193198
TI - A sesquiterpene, dehydrocostus lactone, inhibits the expression of inducible
nitric oxide synthase and TNF-alpha in LPS-activated macrophages.
AB - Nitric oxide (NO) and tumor necrosis factor alpha (TNF-alpha) are the major
mediators produced in activated macrophages which contribute to the circulatory
failure associated with septic shock. A sesquiterpene lactone compound
(dehydrocostus lactone) isolated from the medicinal plant, Saussurea lappa,
inhibited the production of NO in lipopolysaccharide (LPS)-activated RAW 264.7
cells by suppressing inducible nitric oxide synthase enzyme expression. This
compound also decreased the TNF-alpha level in LPS-activated systems in vitro and
in vivo. Thus, dehydrocostus lactone may be a possible candidate for the
development of new drugs to treat endotoxemia accompanied by the overproduction
of NO and TNF-alpha.
PMID- 10193199
TI - Nitric oxide/cGMP mediates the spasmolytic action of 3,4'-dihydroxy-5,5'
dimethoxybibenzyl from Scaphyglottis livida.
AB - Five aromatic compounds, 3,4'-dihydroxy-5,5'-dimethoxybibenzyl (1), batatasin III
(2), coelonin (3), 3,7-dihydroxy-2,4-dimethoxyphenanthrene (4), and 3,7-dihydroxy
2,4,8-trimethoxyphenanthrene (5) were isolated from the orchid Scaphyglottis
livida (Lindley) Schltr. Compounds 1-5 induced a concentration-dependent
inhibition of the spontaneous contractions of the rat ileum with potencies
comparable or higher to that of papaverine. The relaxation evoked by compounds 1
4 was blocked by L-NAME, an inhibitor of nitric oxide synthase. It was also
demonstrated that 1 increased cyclic GMP content in rat ileum rings. Compound 1
induced elevation of cGMP was inhibited by L-NAME and ODQ, inhibitors of nitric
oxide synthase and soluble guanylyl cyclase, respectively. These results indicate
that nitric oxide/cGMP formation constitute the signaling pathway in the
spasmolytic action of compound 1.
PMID- 10193200
TI - Adenosine, the anxiolytic-like principle of the Arillus of Euphoria longana.
AB - According to traditional usage, the extract of Longan Arillus was tested for its
anxiolytic-like effect by application of the Vogel-type anti-conflict method in
mice. The extract indicated significant activity at a dose of 2 g/kg, s.c., and
results of the bioassay-oriented isolation revealed adenosine to be the active
principle. Adenosine produced the anti-conflict effect significantly at a dose of
30 mg/kg, s.c. Adenine, uridine, and 5-methyluridine did not exhibit the effect,
although these compounds were isolated from the extract. Some other related
compounds such as AMP and c-AMP showed no effect, except for inosine. Adenosine
also contributed to the analgesic effect which was observed in the extract by the
writhing method.
PMID- 10193201
TI - Antiviral activities of biflavonoids.
AB - Biflavonoids such as amentoflavone (1), agathisflavone (2), robustaflavone (3),
hinokiflavone (4), volkensiflavone (5), rhusflavanone (7), succedaneflavanone
(9), all isolated from Rhus succedanea and Garcinia multiflora, as well as their
methyl ethers and acetates, volkensiflavone hexamethyl ether (6), rhusflavanone
hexaacetate (8), and succedaneflavanone hexaacetate (10) were evaluated for their
antiviral activities. The inhibitory activities against a number of viruses
including respiratory viruses (influenza A, influenza B, respiratory syncytial,
parainfluenza type 3, adenovirus type 5, and measles) and herpes viruses (HSV-1,
HSV-2, HCMV, and VZV) were investigated. The results indicated that
robustaflavone exhibited strong inhibitory effects against influenza A and
influenza B viruses with EC50 values of 2.0 micrograms/ml and 0.2 microgram/ml,
respectively, and selectivity index values (SI) of 16 and 454, respectively.
Amentoflavone and agathisflavone also demonstrated significant activity against
influenza A and B viruses. Amentoflavone and robustaflavone exhibited moderate
anti-HSV-1 anti-HSV-2 activities with EC50 values of 17.9 micrograms/ml (HSV-1)
and 48.0 micrograms/ml (HSV-2) and SI values of > 5.6 (HSV-1) and > 2.1 (HSV-2)
for amentoflavone; EC50 values of 8.6 micrograms/ml (HSV-1) and 8.5 micrograms/ml
(HSV-2), and SI values of > 11.6 (HSV-1) and > 11.8 (HSV-2) for robustaflavone.
Rhusflavanone demonstrated inhibitory activities against influenza B, measles,
and HSV-2 viruses with SI values of 9.3, 8 and > 6.4, respectively.
Succedaneaflavanone exhibited inhibitory activities against influenza B virus and
VZV with SI values of 15 and < 3.0, respectively.
PMID- 10193202
TI - Low concentrations of the feverfew component parthenolide inhibit in vitro growth
of tumor lines in a cytostatic fashion.
AB - Parthenolide, a clinically useful agent and migraine prophylaxis principle from
the medicinal plant, feverfew (Tanacetum parthenium), was tested on two tumor
cell lines for its ability to inhibit cell growth. At concentrations above 5.0
microM and an exposure time of 24 h, parthenolide inhibited cell growth in an
irreversible fashion. However, at lower concentrations, the effect was
reversible; parthenolide acted in a cytostatic fashion over multiple cell
generations for mouse fibrosarcoma (MN-11) and human lymphoma (TK6) cell lines.
After 24 h exposure to 2.5 microM parthenolide, approx. 85% of cells were able to
continue cell cycling on removal of the chemical, as demonstrated by labeling of
S-phase cells with BrdU. In a clonogenic assay, colony formation was also
unchanged by exposure to this concentration of parthenolide. No indication of
cell synchronization could be found, as evidenced by the lack of appearance of a
peak of mitotic figures when cells were examined at 1 h intervals for 10 h after
drug removal. The mechanism of the reversible growth inhibition is uncertain.
PMID- 10193203
TI - Acute hemodynamic effects of tetramethylpyrazine and tetrandrine on cirrhotic
rats.
AB - The hemodynamic effects of tetramethylpyrazine (TMP) and tetrandrine (TET), both
alkaloids isolated from Chinese herbs Ligusticum wallichii Franch and Stephania
tetrandra S. Moore, respectively, were assessed in anesthetized cirrhotic rats.
TMP induced dose-dependent decreases of portal venous pressure (P.V.P.) and mean
arterial pressure (M.A.P.) after intravenous infusion. The maximum percentage
reduction of P.V.P. after TMP was 3.6 +/- 0.8%, 6.8 +/- 0.5%, and 17.8 +/- 0.6%
of baseline, respectively, for the dosages given (3.0, 9.9 and 30.0 mg/kg).
Similarly, TET induced dose-dependent decreases of P.V.P. and M.A.P. The maximum
percentage reduction of P.V.P. after TET was 5.4 +/- 1.0%, 9.2 +/- 0.8%, and 23.7
+/- 1.2% of baseline, respectively, for the dosages given (2.0, 6.6 and 20.0
mg/kg). Total peripheral resistance was also reduced by TMP as well as TET. Our
results showed that TMP and TET induced P.V.P. reduction in cirrhotic rats,
together with reduction in M.A.P. and total peripheral resistance.
PMID- 10193204
TI - Effects of tetrandrine and fangchinoline on experimental thrombosis in mice and
human platelet aggregation.
AB - Tetrandrine (TET) and fangchinoline (FAN) are two naturally occurring analogues
with a bisbenzylisoquinoline structure. The present study was undertaken to
investigate the effects of TET and FAN on the experimental thrombosis induced by
collagen plus epinephrine (EP) in mice, and platelet aggregation and blood
coagulation in vitro. In the in vivo study, the administration (50 mg/kg, i.p.)
of TET and FAN in mice showed the inhibition of thrombosis by 55% and 35%,
respectively, while acetylsalicylic acid (ASA, 50 mg/kg, i.p.), a positive
control, showed only 30% inhibition. In the vitro human platelet aggregations
induced by the agonists used in tests, TET and FAN showed the inhibitions dose
dependently. In addition, neither TET nor FAN showed any anticoagulation
activities in the measurement of the activated partial thromboplastin time
(APTT), prothrombin time (PT) and thrombin time (TT) using human-citrated plasma.
These results suggest that antithrombosis of TET and FAN in mice may be mainly
related to the antiplatelet aggregation activities.
PMID- 10193205
TI - Quality of herbal remedies from Allium sativum: differences between alliinase
from garlic powder and fresh garlic.
AB - Alliinase (EC 4.4.1.4) has been isolated from commercially available garlic
(Allium sativum L., Alliaceae) powder and was investigated with respect to its
use as ingredient of herbal remedies. The enzyme was purified to apparent
homogeneity and results were compared with those obtained from a sample of fresh
A. sativum var. pekinense. The purification of the enzyme involved a gel
filtration step as well as affinity chromatography on concanavalin-A agarose.
Vmax using L-(+)-alliin as substrate (252 mumol min-1 mg-1) was at the lower
range of data given in the literature (214-390 mumol min-1 mg-1). L-(-)-Alliin
was also accepted as substrate (54 mumol min-1 mg-1). Vmax for alliinase from A.
sativum var. pekinense was at 332 mumol min-1 mg-1 and 90 mumol min-1 mg-1 for L
(+)- and L-(-)-alliin, respectively. The Km values for alliinase from garlic
powder were estimated to be 1.6 mM for L-(+)-alliin and 2.8 mM for L-(-)-alliin.
In contrast to literature values, both temperature and pH optima were somewhat
higher (36 degrees C and pH 7.0 versus 33 degrees C and pH 6.5, respectively).
The enzyme was found to be active in a range from pH 5 to pH 10. Gel
electrophoresis gave evidence that the alliinase obtained from garlic powder
consisted of two slightly different subunits with molecular weights of 53 and 54
kDa whereas alliinase obtained from fresh garlic consists of two identical
subunits. It is assumed that the alliinase gets significantly altered during the
drying process of garlic powder but is still capable to convert alliin to
allicin.
PMID- 10193206
TI - Datura metel: in vitro production of tropane alkaloids.
AB - Hairy root lines of Datura metel were established following infection of aseptic
stem segments with Agrobacterium rhizogenes strain A4 and cultured in hormone
free B5 solid medium. The growth and production of hyoscyamine and scopolamine
(mg/g dry wt.) of these root cultures was encouraged by using B5 liquid medium
with half-strength salts. In these culture conditions, the capacity of the
highest productive root line 25 to excrete scopolamine into the culture medium
rose from 8.7% to 70% when the permeabilizing agent Tween 20 was added for 24 h
to the medium, after 2 and 4 weeks of culture. Using an airlift bioreactor (41)
with modifications in order to increase root anchorage, the Tween 20 treatment
encouraged both growth and alkaloid productivity of cultured root line 25. After
4 weeks their biomass yield was 2.3 mg/l/day and 0.84 mg/l/day of scopolamine was
produced (70% extracellular). The scopolamine released into the culture medium
was separated with an Amberlite XAD-2 column located in the media exit.
PMID- 10193207
TI - Production of the sedative triterpene galphimine B in Galphimia glauca tissue
culture.
AB - A tissue culture method is described for callus formation from Galphimia glauca
(Mapighiaceae) in MS (Murashige & Skoog) medium supplemented with various growth
regulators. Best induction was achieved when using hypocotyls as explants in
medium supplemented with 2 mg/l of 2,4-dichlorophenoxyacetic acid (2,4-D). Major
cellular growth of calluses was obtained with naphthaleneacetic acid (2 mg/l) +
kinetin (1 mg/l). Subcultivation of calluses using various concentrations of 2,4
D allowed the production of the sedative nor-seco-triterpenoid, galphimine B and
a new related compound. The structure of the new constituent was elucidated as 6
acetoxygalphimine B. The highest accumulation of active constituent 1 (1.5 x 10(
2) dry weight) was achieved when 4 mg/l of the hormone were used, and this
experimental condition allowed the detection of only galphimine B. A preliminary
screening of the methanolic extracts prepared from calluses, using the isolated
guinea-pig ileum as a general test system for pharmacological effects,
demonstrated that the most active material was the one with the highest
concentration of galphimine B. Total accumulation of this sedative triterpene, in
the optimized tissue culture conditions, was in the same order of magnitude as
the value quantified for wild plants (4.5 x 10(-2) dry weight).
PMID- 10193208
TI - Acute and chronic effects of ginseng total saponin and amphetamine on fixed
interval performance in rats.
AB - The effect of ginseng total saponin (GTS) on amphetamine (AMPH)-induced
disruption of fixed-interval (FI) responding in rats was examined. GTS (50 mg/kg)
significantly improved the temporal responding impaired by 2 mg/kg of AMPH. A
higher dose of 100 mg/kg GTS disrupted performance when given alone; this
disruption was reversed by a low dose of AMPH (0.5 mg/kg) and tolerance developed
to the effects of GTS with its repeated administration. Neurochemical analysis
revealed that GTS (50 mg/kg) attenuated the increase in striatal dopamine caused
by AMPH leading to the conclusion that brain dopamine may partially mediate the
behavioral effects of GTS.
PMID- 10193209
TI - Formation of nitrogen-containing metabolites from the main iridoids of
Harpagophytum procumbens and H. zeyheri by human intestinal bacteria.
AB - The study of the metabolism of iridoid glycosides from Harpagophytum procumbens
and Harpagophytum zeyheri by human intestinal bacteria, was realized in order to
elucidate compounds responsible for the pharmacological activities of
Harpagophytum. Harpagide, harpagoside and 8-O-p-coumaroyl-harpagide were
transformed into the pyridine monoterpene alkaloid aucubinine B by human fecal
flora and by bacteria isolated from this flora. Aucubinine B was also prepared
from harpagide, harpagoside and 8-O-p-coumaroylharpagide, by beta-glucosidase in
the presence of NH4+.
PMID- 10193210
TI - Composition and antimicrobial activity of the essential oil of Peumus boldus
leaves.
AB - The composition and the antimicrobial activity of the essential oil from the
leaves of Peumus boldus is investigated. Analyses of the oil obtained by
hydrodistillation were carried out by GC and GC-MS using columns of two different
stationary phases. Fractionation of the essential oil by column chromatography on
silica gel was performed to improve identification of some constituents. More
than 90% of the total oil (46 components) was identified, major constituents
being monoterpenes (90.5%), among which limonene (17.0%), p-cymene (13.6%), 1.8
cineole (11.8%), and beta-phellandrene (8.4%) reached the highest percentages.
Determination of the minimal bactericidal or fungicidal concentration against
several microorganisms showed interesting activities towards Streptococcus
pyogenes, Micrococcus sp., and Candida sp.
PMID- 10193211
TI - Bioavailability of ginkgolides and bilobalide from extracts of ginkgo biloba
using GC/MS.
AB - The bioavailability of ginkgolides A, B and bilobalide was studied in rats after
single oral administration of 30, 55 and 100 mg/kg Ginkgo extract EGb 761. The
plasma levels of the terpene lactones were measured by a specific GC/MS method.
The pharmacokinetics of the mentioned substances were found to be dose-linear.
For the lowest dose maximum concentrations were 68, 40 and 159 ng/ml and half
lives 1.7, 2.0 and 2.2 h for ginkgolide A, B and bilobalide, respectively.
Clearance values ranged from 24.2 to 37.6 ml/min/kg.
PMID- 10193212
TI - A cytotoxic chalcone from Faramea salicifolia.
PMID- 10193213
TI - Paediatric intensive care--the way ahead?
PMID- 10193214
TI - The relevance of clinical and radiological measurements in predicting
difficulties in fibreoptic orotracheal intubation in adults.
AB - Resistance to the passage of the tracheal tube has been reported to occur in up
to 36% of patients subjected to orotracheal fibreoptic intubation. In this
prospective study we assessed five radiological measurements of the upper airway
in an attempt to find anatomical causes of obstruction to passage of the tube.
Forty-nine patients undergoing fibreoptic orotracheal intubation under general
anaesthesia were studied. Pre-operatively, the Mallampati grade and the
thyromental distance were assessed. The plain films, CT scans or MR images of the
cervical spine were used for measurement of the position of the vocal cords, the
length of the epiglottis and the size of the tongue. The resistance to the
passage of the tube was graded as none, mild, moderate or severe. The length of
the epiglottis and the size of the tongue, but not the position of the vocal
cords, had positive correlations with the severity of impingement. The pre
operative bedside tests did not correlate with difficulties in fibreoptic
intubation.
PMID- 10193215
TI - Side-effects of epidural infusions of opioid bupivacaine mixtures.
AB - The incidence of side-effects occurring with epidural diamorphine (0.05 mg.ml-1),
fentanyl (2.0 micrograms.ml-1), methadone (0.1 mg.ml-1), morphine (0.05 mg.ml-1)
and pethidine (1.0 mg.ml-1) used by infusion in combination with bupivacaine has
been compared. One hundred and sixty patients were studied, 32 receiving each
opioid. The incidence of nausea and vomiting was significantly greater with
morphine than fentanyl (p = 0.0097) and pethidine (p = 0.0021). The incidence of
pruritus was significantly greater with morphine and diamorphine than with
methadone (p = 0.012) and pethidine (p = 0.027). Morphine was also associated
with a significantly greater incidence of urinary retention than pethidine (p =
0.012) and methadone (p = 0.025).
PMID- 10193216
TI - Influence of anaesthesia on defibrillation threshold.
AB - Internal cardioverter-defibrillator implantation can be performed under local or
general anaesthesia. Whether the technique of general anaesthesia influences the
defibrillation threshold remains a matter of debate. We therefore compared, in a
prospective, randomised clinical study, the effect of intravenous anaesthesia
using propofol with inhalational anaesthesia using isoflurane on the
defibrillation threshold in 68 patients scheduled for transvenous single-lead
internal cardioverter-defibrillator implantation. Defibrillation threshold was
measured at implantation and at device testing 1 week and 1 month after
implantation. Patients acted as their own controls. Neither the anaesthetic
technique nor the duration of anaesthesia was associated with significant changes
in the defibrillation threshold. We conclude that in this group of high-risk
patients, both types of anaesthesia are acceptable techniques for internal
cardioverter-defibrillator implantation and testing.
PMID- 10193217
TI - Comparison of 0.75% levobupivacaine with 0.75% racemic bupivacaine for peribulbar
anaesthesia.
AB - In a single centre, randomised, double-blind study 50 patients scheduled for
intra-ocular surgery received 0.75% levobupivacaine or 0.75% racemic bupivacaine
for peribulbar anaesthesia. There were no significant differences in the mean
(SD) volume of levobupivacaine (11 (2.7) ml) or racemic bupivacaine (10 (2.6) ml)
required, time to satisfactory block (levobupivacaine-13 (5.6) min; racemic
bupivacaine-11 (4.4) min), peri-operative pain scores or frequency of adverse
events between levobupivacaine and racemic bupivacaine. The safer side-effect
profile of levobupivacaine may offer significant advantages in the elderly
population undergoing cataract extraction in whom intercurrent disease is common.
PMID- 10193218
TI - Prophylactic anti-emetic therapy with granisetron, droperidol and metoclopramide
in female patients undergoing middle ear surgery.
AB - The efficacy of granisetron, droperidol and metoclopramide for the prevention of
postoperative nausea and vomiting in female patients undergoing middle ear
surgery was compared. In a randomised, double-blind study, 180 patients received
granisetron 40 micrograms.kg-1, droperidol 20 micrograms.kg-1 or metoclopramide
0.2 mg.kg-1 given intravenously immediately before induction of anaesthesia (n =
60 for each). A standardised general anaesthetic technique was employed
throughout. A complete response, defined as no postoperative nausea and vomiting
and no need for another rescue anti-emetic, during the first 3 h after
anaesthesia was achieved in 83%, 58% and 55% of patients who had received
granisetron, droperidol and metoclopramide, respectively. The corresponding
incidence during the next 21 h after anaesthesia was 85%, 54% and 47% (p < 0.05).
No clinically important adverse effects were observed in any of the groups. We
conclude that prophylactic therapy with granisetron is superior to droperidol or
metoclopramide in the prevention of postoperative nausea and vomiting after
middle ear surgery.
PMID- 10193219
TI - Neuromuscular blocking effects and train-of-four fade with cisatracurium:
comparison with other nondepolarising relaxants.
AB - Neuromuscular blocking drugs exhibit different degrees of fade in response to
train-of-four stimulation believed to represent their relative prejunctional
effects. The present study was designed to compare the train-of-four fade after
cisatracurium and compare this with other commonly used muscle relaxants. Train
of-four fade during onset and recovery of block were recorded after
administration of cisatracurium 0.05 or 0.1 mg.kg-1, atracurium 0.5 mg.kg-1,
vecuronium 0.08 mg.kg-1, mivacurium 0.15 mg.kg-1 or rocuronium 0.6 mg.kg-1 to
patients anaesthetised with fentanyl, nitrous oxide and a propofol infusion.
Neuromuscular monitoring was by stimulation of the ulnar nerve and recording the
force of contraction of the adductor pollicis muscle. The onset and recovery of
block were also measured. Train-of-four fade during onset of block was greater
with the lower dose of cisatracurium compared with the higher dose of
cisatracurium and all other relaxants. Train-of-four fade during recovery was
similar. The median times (and ranges) for the onset of maximum block were 3.4
(2.1-5.6), 1.5 (1.2-2.3), 2.1 (1.2-2.6), 2.0 (1.5-2.7) and 1.0 (0.7-1.3) min for
cisatracurium 0.1 mg.kg-1 and atracurium, mivacurium, vecuronium and rocuronium,
respectively. The median times (and ranges) for the recovery of T1 to 25% of
control and to a train-of-four ratio of 0.8 were 41 (21-50) and 65 (40-78); 43
(37-54) and 69 (58-79); 15 (11-20) and 25 (19-30); 31 (23-46) and 60 (45-117);
and 33 (18-57) and 50 (28-76) min following cisatracurium, 0.1 mg.kg-1,
atracurium, mivacurium, vecuronium and recuronium, respectively.
PMID- 10193220
TI - The intubating laryngeal mask. Results of a multicentre trial with experience of
500 cases.
AB - A multicentre trial of the use of the intubating laryngeal mask was carried out
at seven centres in the United Kingdom using the same agreed protocol. Lung
ventilation followed by blind tracheal intubation through the intubating
laryngeal mask was attempted on 500 ASA grade 1 and 2 patients. It was possible
to insert the intubating laryngeal mask in all 500 cases. Ventilation via the
intubating laryngeal mask was described as satisfactory in 475 (95%) cases,
difficult in 20 (4%) cases and unsatisfactory in 5 (1%) cases. Blind tracheal
intubation through the intubating laryngeal mask was possible in 481 (96.2%)
cases within three attempts. Intubation was successful at the first attempt in
399 (79.8%) cases, at the second attempt in 62 (12.4%) cases and at the third
attempt in 20 (4%) cases. The tracheas of 19 (3.8%) patients were not
successfully intubated within the three attempts. Ventilation via the intubating
laryngeal mask was described as unsatisfactory during two of these cases but
oxygenation remained satisfactory in spite of this. Seventeen of the 19 failures
occurred during the individual operator's first 20 attempts. The intubating
laryngeal mask provides a successful method for blind tracheal intubation in a
large proportion of cases and appears to be superior to the standard laryngeal
mask airway for this purpose. The intubating laryngeal mask may be of use when
tracheal intubation has failed using conventional methods.
PMID- 10193221
TI - Predictable normocapnia [correction of normocapnoea] in controlled ventilation of
infants with Jackson Rees or Bain system.
AB - We have devised a formula for ventilator settings which provide normal minute
ventilation without rebreathing during controlled ventilation using a Jackson
Rees or Bain system. As VT = VS + VF- VL, where VT = delivered tidal volume, VS =
set tidal volume, VF = the volume of fresh gas entering during the inspiratory
phase and VL = the lost volume due to the compliance of the system, VS was
derived: VS = VL + VT x [1-b/(1 + a)] where a = expiratory-to-inspiratory ratio
and b = the ratio of fresh gas flow to the minute ventilation. It was evaluated
in 62 infants. Arterial partial pressure of carbon dioxide (mean (SD)) was 4.6
(0.5) kPa (35 (4) mmHg) with a range of 3.42-5.78 kPa (26-44 mmHg). The 90th
percentile was 5.1 kPa (39 mmHg). It is concluded that predictable normocapnia
[corrected] can be conveniently achieved in infants in controlled ventilation
with Jackson Rees or Bain system if our formula is applied.
PMID- 10193222
TI - Severity of illness scoring systems and performance appraisal.
AB - A large number of severity of illness scoring systems have been developed and
they are widely used in intensive care practice. However, they are complex
systems with their basis in mathematics. To use such systems effectively, it is
important to appreciate what factors influence their performance so that they can
be compared fairly and used most appropriately. The purpose of this review is to
describe the methods commonly used to assess the various facets of performance in
severity of illness scoring systems. The performance of the most frequently used
scoring systems in adult intensive care practice are presented. The shortfalls,
misuse and strengths of scoring systems are also discussed.
PMID- 10193223
TI - Gamma-hydroxybutyric acid: an emerging recreational drug.
AB - Gamma-hydroxybutyric acid (GHB) is no longer used as an anaesthetic induction
agent because of the high incidence of myoclonic seizures and vomiting. However,
it is used occasionally in Europe for the treatment of narcolepsy, alcohol
dependence and opiate dependence. Since the early 1990s, GHB has become a drug of
abuse in youths for its euphoric, sedative and anabolic effects. Common adverse
effects include a rapid onset of drowsiness, nausea, vomiting, myoclonic seizures
and coma of short duration. Clinicians should be alert for these adverse effects
and consider the possibility of GHB abuse in young adults with unusual clinical
presentations in the emergency department.
PMID- 10193224
TI - Tracheal intubation through the intubating laryngeal mask in a patient with a
fixed flexed neck and deviated larynx.
AB - Insertion of the conventional laryngeal mask is more difficult or impossible when
the patient's head and neck are in either the neutral or flexed position. The
intubating laryngeal mask is best inserted when the patient's head is supported
by a pillow, without placing the head and neck into the Magill position;
therefore, insertion of this modified mask may be less difficult than the
conventional mask in the patient with a flexed neck. We report a case of
successful insertion of the intubating laryngeal mask and subsequent tracheal
intubation through the mask using a fibre-optic bronchoscope, in a patient with a
flexed neck in whom tracheal intubation using several methods had been difficult
previously.
PMID- 10193225
TI - General anaesthesia for thyroplasty.
AB - A new anaesthetic technique is described for thyroplasty. Thyroplasty was
performed to restore the voice in unilateral vocal cord paralysis. After skin
incision and dissection down to the larynx, a window was cut in the thyroid ala
and a silastic wedge used to displace the vocal cord medially. The required size
of this wedge was determined by pre-operative computerized tomography scanning of
the larynx. At this point the patient had to be awake and cooperative to allow
repeated phonation to facilitate correct displacement of the vocal cord.
PMID- 10193226
TI - Major vascular surgery in a patient with sickle cell disease.
AB - We report a patient with homozygous sickle cell disease who underwent
femoropopliteal bypass for claudication on walking 10m. Isotope studies showed a
blood flow in his left femoral artery of only 0.808 ml. 100ml.min-1. The
potential problems of sickle cell disease combined with peripheral vascular
disease were probably reduced in this patient because he had an increased fetal
haemoglobin level of 13%. Despite the femoral artery being clamped for 100 min,
no sickling crisis occurred.
PMID- 10193227
TI - Use of capnography delaying the diagnosis of tracheal intubation.
AB - There was a delay in making the correct diagnosis of tracheal intubation in a
parturient who developed severe bronchospasm after intubation because we relied
on the capnogram.
PMID- 10193228
TI - Use and safety of percutaneous tracheostomy in intensive care. Report of a postal
survey of ICU practice.
AB - A brief questionnaire was sent to 231 clinical directors of intensive care units
in England and Wales to investigate the use of percutaneous tracheostomy. There
was a 76% response rate. Percutaneous tracheostomies were in use in 78.4% of
units. The Ciaglia technique was the most commonly used, with 31.3% routinely
using fibreoscopy as part of their technique. Only 12% of units routinely
provided long-term follow up of their percutaneous tracheostomies. Overall, 78.4%
thought that percutaneous tracheostomy was safe and 66.7% considered percutaneous
tracheostomy to be the technique of choice for Intensive Care patients.
Percutaneous tracheostomy is now a well-established technique. However, the
limited use of fibreoscopy and the lack of long-term follow-up are areas of
concern.
PMID- 10193229
TI - Transcutaneous CO2/O2 and CO2/air suction in patients undergoing cataract surgery
with retrobulbar anaesthesia.
AB - We investigated transcutaneous partial CO2 and O2 pressures and respiratory rate
in unpremedicated elderly patients of ASA physical status 1 to 3 who underwent
cataract surgery under retrobulbar anaesthesia. In group A no air suction was
used. In group B suction was applied under the sterile drapes to avoid
rebreathing of CO2. In group A transcutaneous partial CO2 pressure and
respiratory rate significantly increased compared with baseline, whereas in group
B they remained constant. In both groups transcutaneous partial O2 pressure and
oxygen saturation as measured by pulse oximetry significantly rose after
insufflating oxygen 31.min-1. Heart rate and mean arterial blood pressure
remained constant. Our results demonstrate that the application of suction near
the patient's head prevents CO2 rebreathing and subsequent hypercapnia associated
with an elevated respiratory rate. The use of suction makes it unnecessary to
raise oxygen administration. Suction combined with monitoring of partial CO2
pressure using transcutaneous sensors should be used in all ophthalmological
operations under retrobulbar anaesthesia.
PMID- 10193231
TI - Evaluation of remifentanil for control of haemodynamic response to tracheal
intubation.
AB - We have studied the effect of three bolus doses of remifentanil on the
haemodynamic response to laryngoscopy and tracheal intubation. Using a double
blind design, 80 ASA 1 or 2 patients presenting for elective surgery received
saline placebo or remifentanil 0.25, 0.5 or 1.0 microgram.kg-1 by random
allocation. Anaesthesia was induced with thiopentone 5-7 mg.kg-1 and followed
immediately by the study medication given as a bolus over 30s. Muscle relaxation
was provided with rocuronium 0.75 mg.kg-1. The patients' tracheas were intubated
under direct laryngoscopy 1 min later. Noninvasive arterial blood pressure and
heart rate were recorded immediately before induction of anaesthesia and then at
intervals until 5 min after tracheal intubation. There was a significant increase
in heart rate (p < 0.01) and systolic arterial pressure (p < 0.01) in all groups
after tracheal intubation. However, this was short-lived and of a smaller
magnitude in the remifentanil 1 microgram.kg-1 group in which the increase was
significantly lower than in the control group (p < 0.01).
PMID- 10193230
TI - EMLA patch for spinal puncture. A comparison of EMLA patch with lignocaine
infiltration and placebo patch.
AB - We have prospectively assessed pain and anxiety of spinal puncture in 180 adult
patients randomly allocated to one of three equal groups. On the morning of
surgery group 1 had an EMLA patch, whereas group 2 and 3 had placebo patches.
Group 2 also had infiltration analgesia with 2 ml lignocaine 2% with adrenaline,
immediately before the block. Spinal anaesthesia was performed with 25 gauge
sharp needles without introducer or 25,27 gauge blunt needles with 20,22 gauge
introducers. Patients assessed the spinal puncture pain on a 10-cm visual
analogue scale immediately after removal of the needle. Pain scores were
significantly lower in group 1 (EMLA), median 0.75, than in group 2 (placebo,
infiltration analgesia), median 1.75, and group 3 (placebo), median 1.80, p <
0.0001. Pain intensity was less than expected in more patients in the EMLA group
than in the other two groups, p = 0.034. However, the decision to accept/reject
spinal anaesthesia in the future was not influenced by the pain of lumbar
puncture. We conclude that application of an EMLA patch is a simple and effective
method to provide adequate analgesia for spinal puncture, which also helps to
allay patients' fears of spinal anaesthesia.
PMID- 10193232
TI - Anaesthesia for ECT.
PMID- 10193233
TI - Acute pain services: a 24-h commitment.
PMID- 10193234
TI - Elective admission of patients to intensive care or high dependency following
major surgery.
PMID- 10193235
TI - A serious breathing system fault.
PMID- 10193237
TI - Infusion devices: most do not measure the volume infused.
PMID- 10193236
TI - Pharyngolaryngeal morbidity with the intubating laryngeal mask airway.
PMID- 10193239
TI - Cricoid pressure and laryngoscopy.
PMID- 10193238
TI - The epidural potato!
PMID- 10193240
TI - Anaesthetic monitors--the vanishing trace.
PMID- 10193241
TI - Xenon as a replacement for nitrous oxide.
PMID- 10193242
TI - The sitting position for spinal anaesthesia.
PMID- 10193243
TI - Universal Shrader outlets on oxygen regulators.
PMID- 10193244
TI - Latex allergy--strategies for management.
PMID- 10193245
TI - Spinal anaesthesia for emergency caesarean section in an achondroplastic dwarf.
PMID- 10193246
TI - A funny thing happened on the way to the scanner...
PMID- 10193247
TI - Attention deficit hyperactivity disorder.
PMID- 10193248
TI - Albumin: saint or sinner?
PMID- 10193249
TI - Case-control study of current validity of previously described risk factors for
SIDS in The Netherlands.
AB - This study aimed to assess whether previously established risk factors for sudden
infant death syndrome (SIDS) are still valid now that the incidence in the
Netherlands has dropped to 0.26 per 1000 liveborn infants. A distinction was made
between immutable and mutable risk factors. This case-control study (part of the
European Concerted Action on SIDS) comprised 73 SIDS cases and 146 controls and
lasted from March 1995 to September 1996. Adjustments were made for sleeping
position and bedding factors by treating them as covariables. Apart from these
factors, well known risk factors that remain of importance in the Netherlands
are: male sex, young maternal age, twins, and low socioeconomic status. These
factors are largely immutable. Other well known risk factors which might reflect
attitudes to child care and could possibly be mutable are: smoking, alcohol
consumption by the mother, bottle feeding, and change of babycare routine.
Intervention strategies should focus on early signalling, thereby assisting
parents in changing these unfavourable parenting attitudes. Information on
optimal child care and extra support by public health nurses specifically aimed
at families at risk could help to decrease further the incidence of SIDS in the
Netherlands.
PMID- 10193250
TI - Deletion polymorphism of the angiotensin converting enzyme gene predicts
persistent proteinuria in Henoch-Schonlein purpura nephritis.
AB - OBJECTIVE: To study the influence of deletion/insertion polymorphism in the 16th
intron of the angiotensin converting enzyme (ACE) gene on clinical manifestations
of Henoch-Schonlein purpura nephritis. STUDY DESIGN: Cross sectional study. ACE
gene polymorphism was determined in patients (4-15 years old at onset) with
Henoch-Schonlein purpura nephritis (n = 40) and compared with that in patients
with IgA nephropathy (n = 79). MAIN OUTCOME MEASURES: ACE genotypes, systemic
blood pressures, urine protein excretion rate, haematuria, creatinine clearance,
serum ACE activities. RESULTS: The initial clinical manifestations of both Henoch
Schonlein purpura nephritis and IgA nephropathy were no different among
homozygotes for insertion (II) and deletion (DD), and heterozygotes (ID) for the
ACE gene. In patients with Henoch-Schonlein purpura nephritis, the incidence of
moderate to heavy proteinuria at four and eight years after onset was more than
five times higher in the DD genotype than in the II or ID genotypes. No such
trend was seen in patients with IgA nephropathy. The number of patients with
Henoch-Schonlein purpura nephritis in whom proteinuria resolved at four and eight
years after onset was significantly lower in the DD genotype compared with the II
genotype, whereas no differences were detected among the three different
genotypes in patients with IgA nephropathy. Plasma ACE activities in patients
with the DD genotype were significantly higher than in those with non-DD
genotypes. CONCLUSIONS: The ACE DD genotype predicts persistent proteinuria in
Henoch-Schonlein purpura nephritis. The proteinuria might be related to a
defective angiotensin system which is genetically determined by the D/I
polymorphism.
PMID- 10193251
TI - Production of antibodies to staphylococcal superantigens in atopic dermatitis.
AB - Staphylococcal superantigens (SAG) are implicated in the inflammation of atopic
dermatitis. As SAG mediated diseases may be modified by specific antibodies, the
antibody response to SAG in atopic dermatitis was investigated. Immunoglobulin
(Ig) G to staphylococcal enterotoxin A (SEA), staphylococcal enterotoxin B (SEB),
and toxic shock syndrome toxin 1 (TSST-1) were measured by sandwich enzyme linked
immunosorbent assay (ELISA) in 74 children with atopic dermatitis and 111
controls. Controls had detectable IgG to SEA, SEB, and TSST-1, which increased
with age. Atopic dermatitis subjects had an increased response to SEB at 6 months
to 2 years (76% v 42%) and 2 to 7 years (79% v 57%), and equivalent responses to
SEA and TSST-1, compared to controls. It is suggested that increased responses to
SEB relate to increased colonisation and hence exposure to superantigen producing
staphylococcus in atopic dermatitis, and that inflammation of atopic dermatitis
is not caused by an inability to make antibody to SAG.
PMID- 10193252
TI - Randomised controlled trial of aminophylline for severe acute asthma.
AB - OBJECTIVES: To determine whether children with severe acute asthma treated with
large doses of inhaled salbutamol, inhaled ipratropium, and intravenous steroids
are conferred any further benefits by the addition of aminophylline given
intravenously. STUDY DESIGN: Randomised, double blind, placebo controlled trial
of 163 children admitted to hospital with asthma who were unresponsive to
nebulised salbutamol. RESULTS: The placebo and treatment groups of children were
similar at baseline. The 48 children in the aminophylline group had a greater
improvement in spirometry at six hours and a higher oxygen saturation in the
first 30 hours. Five subjects in the placebo group were intubated and ventilated
after enrollment compared with none in the aminophylline group. CONCLUSIONS:
Aminophylline continues to have a place in the management of severe acute asthma
in children unresponsive to initial treatment.
PMID- 10193253
TI - Persistent cough: is it asthma?
AB - The aim of this study was to determine if children in the community with
persistent cough can be considered to have asthma. A validated questionnaire was
given to the parents of 1245 randomly selected children aged 6-12 years. Atopy
was measured with skin prick tests. Children with persistent cough had less
morbidity and less atopy compared with children with wheeze. Although the
syndrome commonly referred to as "cough variant asthma" could not be shown in
this study, a significant number of children with persistent cough had been
diagnosed as having asthma and were treated with asthma medications including
inhaled corticosteroids. Studies are urgently needed to determine the appropriate
treatment for children with persistent cough.
PMID- 10193255
TI - Management of the impalpable testis: the role of laparoscopy.
AB - PURPOSE: To evaluate the use of laparoscopy in the management of the impalpable
testis. DESIGN: A retrospective analysis of the clinical findings, interventions,
and outcome in 87 consecutive boys undergoing laparoscopy for 97 impalpable
testes. RESULTS: Fifty seven testes were either absent (n = 35) or present as a
small remnant (n = 22), which was removed at contemporaneous groin exploration.
There were 27 intra-abdominal testes, including four hypoplastic testes, which
were removed laparoscopically. The 13 remaining viable testes were located in the
groin. Conventional orchidopexy followed laparoscopy for 21 testes, and was
successful in 17 cases. Two stage laparoscopically assisted Fowler Stevens
orchidopexies were performed for 13 intra-abdominal testes, with eight
satisfactory results. Ultrasound evaluation significantly reduced the number of
conventional orchidopexies following laparoscopy. IMPLICATIONS: Laparoscopy is a
rational and safe approach for precise localisation of the impalpable testis.
Laparoscopically assisted two stage orchidopexy is a successful treatment
procedure for intra-abdominal testes.
PMID- 10193254
TI - Randomised trial of three doses of inhaled nitric oxide in acute respiratory
distress syndrome.
AB - BACKGROUND: Inhaled nitric oxide (iNO) is a potential therapeutic agent for the
management of acute respiratory distress syndrome (ARDS). Concerns remain,
however, regarding the potential toxicity from iNO and/or its oxidative
derivatives and methaemoglobinaemia. AIMS: To determine the risk of toxicity from
iNO, which includes worsening of lung injury, a prospective study evaluating the
acute effects of three concentrations of iNO on gas exchange and haemodynamics in
12 children with ARDS was performed in a tertiary paediatric intensive care unit.
INTERVENTION: iNO was administered for one hour at three concentrations (1, 10,
and 20 parts per million (ppm)) in a random order of possible dosing schedules to
avoid dose accumulation bias. Arterial blood gas, methaemoglobin concentrations,
and haemodynamic parameters were obtained at baseline before commencement of iNO,
at the end of each study hour, and after iNO was discontinued. Nitric oxide and
nitrogen dioxide concentrations were continuously monitored during the study.
RESULTS: iNO significantly improved the oxygenation ratio (Pao2/Fio2) from a mean
(SEM) baseline of 11.9 (1.7) kPa to 20 (3.9) kPa, 24 (4.5) kPa, and 21.6 (3.9)
kPa at 1, 10, and 20 ppm iNO, respectively. There was no significant difference
in the improvement in oxygenation achieved between the three concentrations.
Correspondingly, there was a significant improvement in oxygenation index (pre
iNO 28.3 (5) v post-iNO 18 (3) (1 ppm), 15 (3) (10 ppm), 16 (3) (20 ppm)). No
toxicity from methaemoglobinaemia or nitrogen dioxide was seen during iNO
administration. CONCLUSION: The results show that a low concentration of iNO (1
ppm) is as effective as higher concentrations (10 and 20 ppm) in improving
oxygenation in children with ARDS and may be important in minimising toxicity
during iNO use.
PMID- 10193256
TI - Parental view of epilepsy in Angelman syndrome: a questionnaire study.
AB - PURPOSE: To explore parents' opinions and concerns about seizures,
anticonvulsants, and the effect of treatment in children with Angelman syndrome.
DESIGN: A postal questionnaire was sent to members of one of the UK lay groups
for Angelman syndrome (ASSERT) who had a child affected by Angelman syndrome. The
questionnaire requested general medical information and information about the
epilepsy, its treatment, and treatment responses. RESULTS: One hundred and fifty
questionnaires were sent out with an ASSERT routine mailing and 78 completed
questionnaires were returned. Forty three patients were boys and 35 were girls;
ages ranged from 1.7 to 25 years (mean 7.5 years). The overall general clinical
and cytogenetic data were mostly consistent with previous reports. Epilepsy was
reported in 68 children, most of whom had a detectable cytogenetic deletion. The
most common seizure types reported by the families were absence seizures, tonic
clonic seizures, drop attacks, and myoclonic seizures; in four patients only
febrile seizures occurred. The age at onset of the seizures was < 2 years in more
than half of the patients. Anti-epileptic drug treatment with valproate (VPA),
clonazepam (CZP), and lamotrigine (LTG) as monotherapy or a combination of VPA
and CZP or VPA and LTG was more often viewed favourably and considered effective
with fewer side effects on the child's behaviour and alertness, versus more
frequent adverse effects and increased frequency and severity of seizures with
carbamazepine (CBZ) and vigabatrin (VGB) in monotherapy or in combination with
other anti-epileptic drugs. Seizures did tend to improve with age but were still
present and disabling at older ages. CONCLUSIONS: This is the first study to
record parents' opinions about seizures, anti-epileptic drugs, and treatment
responses in children with Angelman syndrome, and it is one of the largest series
on epilepsy and Angelman syndrome to be reported to date.
PMID- 10193257
TI - Social disadvantage, family composition, and diabetes mellitus: prevalence and
outcome.
AB - OBJECTIVE: To investigate the relation between social disadvantage and family
composition on diabetes prevalence and diabetes care outcome. DESIGN:
Retrospective audit in the south west of England of 801 children with diabetes
mellitus. MAIN OUTCOME MEASURES: Prevalence of diabetes in relation to the
Townsend index. Admissions to hospital with diabetes related problems, glycated
haemoglobin, time spent in hospital, outpatient attendance rates. RESULTS: There
was no association between social status and diabetes prevalence. Social
deprivation increased the likelihood of admission for hypoglycaemia. Children
living with a single parent were more likely to be admitted to hospital with a
diabetes related problem and stay in hospital longer. Having either a parent with
diabetes or a single parent increased the rates of clinic non-attendance. No
association was identified between medium term diabetes control and either social
disadvantage or single parent status. CONCLUSIONS: Social disadvantage has no
effect on diabetes prevalence and little on diabetes outcome in childhood. Family
structure and parental diabetes have adverse effects on some aspects of diabetes
outcome.
PMID- 10193258
TI - Hypertonic saline test for the investigation of posterior pituitary function.
AB - The hypertonic saline test is a useful technique for distinguishing partial
diabetes insipidus from psychogenic polydipsia, and for the diagnosis of complex
disorders of osmoreceptor and posterior pituitary function. However, there is
little information concerning its use in childhood. The experience of using this
test in five children (11 months to 18 years) who presented diagnostic problems
is reported. In two patients, in whom water deprivation tests were equivocal or
impractical, an inappropriately low antidiuretic hormone (ADH) concentration (< 1
pmol/l) was demonstrated in the presence of an adequate osmotic stimulus (plasma
osmolality > 295 mosmol/kg). In two children--one presenting with adipsic
hypernatraemia and the other with hyponatraemia complicating desmopressin
treatment of partial diabetes insipidus--defects of osmoreceptor function were
identified. Confirming a diagnosis of idiopathic syndrome of inappropriate ADH
secretion (SIADH) was possible in a patient with no other evidence of pituitary
dysfunction. The hypertonic saline test was well tolerated, easy to perform, and
diagnostic in all cases.
PMID- 10193259
TI - Pancreatic exocrine and endocrine function after pancreatectomy for persistent
hyperinsulinaemic hypoglycaemia of infancy.
AB - AIM: To evaluate long term detailed pancreatic endocrine and exocrine function in
children with persistent hyperinsulinaemic hypoglycaemia of infancy (PHHI) after
85-95% pancreatectomy. METHODS: Six children with PHHI between 0.9 and 12.7 years
after pancreatic resection underwent clinical and investigative follow up at 1.0
to 14.9 years of age. One child with PHHI who had not had pancreatectomy was also
assessed. Standard endocrine assessment, pancreatic magnetic resonance imaging
(MRI), and detailed direct and indirect tests of exocrine pancreatic function
were performed. RESULTS: Pancreozymin-secretin stimulation test results were
normal in only one child, borderline in two, and deficient in four, one of whom
requires daily pancreatic enzyme supplements. Pancreolauryl tests performed in
three children were borderline in two and abnormal in the other. Only one child
had low faecal chymotrypsin values. One child developed insulin dependent
diabetes at 9 years and two children at 1.0 and 13.3 years require diazoxide to
maintain normoglycaemia. MRI showed no major regrowth of the pancreatic remnant
after resection (n = 5). CONCLUSIONS: Clinical evidence of endocrine or exocrine
dysfunction has developed in only two patients to date, but detailed pancreatic
function testing suggests subclinical deficiency in all but one of our patients
with PHHI. Although 95% pancreatectomy results in postoperative control of blood
glucose, subclinical pancreatic insufficiency is present on long term follow up
and development of diabetes mellitus and exocrine failure remain ongoing risks.
PMID- 10193260
TI - Long-term follow up of persistent hyperinsulinaemic hypoglycaemia of infancy.
AB - Twenty six children with hypoglycaemia were diagnosed and followed between 1975
and 1995. Diagnosis was confirmed by a high insulin:glucose ratio, and low free
fatty acid and 3-hydroxybutyrate on fasting. All patients were treated with
diazoxide at a maximum dose of 20 mg/kg/day. Requirement of a higher dose was
considered as a failure of medical treatment and an indication for surgery.
Sixteen children Responded to diazoxide; 10 failed to respond and underwent
pancreatic resection. Six of the latter group started with symptoms in the
neonatal period. Eleven of the 26 children have neurological sequelae. Head
growth and neurological outcome correlated well. Additionally, non-specific
electroencephalogram abnormalities (slow waves) appear to be indicative of
subclinical hypoglycaemia during follow up.
PMID- 10193262
TI - Molecular mimicry in autoimmune disease.
PMID- 10193261
TI - Hyperinsulinism: molecular aetiology of focal disease.
AB - Persistent hypoglycaemia in infancy is most commonly caused by hyperinsulinism. A
case is reported of the somatic loss of the maternal 11p in an insulin secreting
focal adenoma in association with a germline SUR-1 mutation on the paternal
allele in a baby boy with hyperinsulinism diagnosed at 49 days old. A reduction
to homozygosity of an SUR-1 mutation is proposed as a critical part of the cause
of focal hyperinsulinism.
PMID- 10193263
TI - Primary pulmonary hypertension in childhood.
PMID- 10193264
TI - An analysis of the new educational demands in paediatric postgraduate training.
PMID- 10193265
TI - Who needs a liver transplant? (new disease specific indications).
PMID- 10193266
TI - Cough, wheeze and sleep.
PMID- 10193267
TI - Obstructive sleep apnoea in children.
PMID- 10193268
TI - Men need masculinism.
PMID- 10193269
TI - Randomised controlled trial of sucrose by mouth for the relief of infant crying
after immunisation.
PMID- 10193270
TI - Randomised controlled trial of sucrose by mouth for the relief of infant crying
after immunisation.
PMID- 10193271
TI - Munchausen syndrome by proxy abuse perpetrated by men.
PMID- 10193272
TI - Improved performance with single dose phosphodiesterase inhibitor?
PMID- 10193273
TI - Gastrointestinal tonometry comes of age?
PMID- 10193274
TI - Characteristics of time-dependent PCO2 tonometry in the normal human stomach.
AB - Factors that affect PCO2 measurement in balloon saline during gastrointestinal
tonometry are unclear. They include carbon dioxide diffusion rate, correction
factors for calculation of equilibrium PCO2 from measurements at saline dwell
times that are shorter than needed for full equilibration, role of blood-gas
analyser bias during ex vivo PCO2 measurements in saline, and normal values for
intragastric PCO2 (PiCO2) and intramucosal pH (pHi) at equilibrium, and their
differences from blood values. In a laboratory study, normal PCO2 changes in a
saline-filled tonometer balloon placed in a saline bath at constant PCO2 were
described by a non-linear model, with a half-time of mean 4.4 min and 95%
equilibration at mean 83 min. In a study in 20 healthy volunteers, PiCO2 build up
in a saline-filled tonometer balloon placed in the stomach, measured at dwell
times of 10, 20, 30 and 60 min, was slightly (P < 0.05) slower than in vitro,
with a half-time of mean 5.8 min and 95% equilibration at mean 110 min.
Correction factors to derive equilibrium PiCO2 at short dwell times and
independently from blood-gas analyser bias were calculated. The factors differed
(P < 0.05) from those currently provided by the manufacturer. Normal threshold
values (mean) were: equilibrium PiCO2 < or = 6.6 kPa, pHi > or = 7.33, PiCO2 to
blood PCO2 difference < or = 1.1 kPa and pH difference > or = -0.06. PiCO2 did
not differ from, and was directly related to, blood PCO2. These values provide a
reference base for other studies and show that gastric mucosal PCO2 depends on
alveolar ventilation if blood flow is adequate.
PMID- 10193275
TI - Gastric tonometry: in vivo comparison of saline and air tonometry in patients
with cardiogenic shock.
AB - Measurement of gastric intramucosal pH (pHi) has been advocated to assess gastric
perfusion. Regional PCO2 (rPCO2) values are measured using saline tonometry
(rsPCO2) and more recently using air tonometry (raPCO2). We compared 237
measurements of saline and air tonometry in 19 consecutive, severely ill patients
(mean age 59 (range 31-76) yr, 19 males, APACHE II 22 +/- 7) with cardiogenic
shock. Equilibration period was set to 90 min. Nineteen independent paired
samples of mean raPCO2 and mean rsPCO2 of each patient showed good correlation (r
= 0.93, P < 0.001). Mean raPCO2 was 6.5 (1.8) kPa and mean rsPCO2 6.8 (2.4) kPa.
PCO2 measured by saline was significantly higher than that measured by air (P <
0.05). Bland and Altman analysis showed a bias (mean rsPCO2-mean raPCO2) of 0.3
kPa and a precision of 1.2 kPa. Agreement between the two methods decreased with
increasing rPCO2 concentrations. Although air tonometry of rPCO2 is a promising
technique, a systematic disagreement with saline tonometry at high rPCO2 values
requires further investigation and cautious interpretation of these values.
PMID- 10193276
TI - Airway closure, atelectasis and gas exchange during general anaesthesia.
AB - Airway closure and the formation of atelectasis have been proposed as important
contributors to impairment of gas exchange during general anaesthesia. We have
elucidated the relationships between each of these two mechanisms and gas
exchange. We studied 35 adults with healthy lungs, undergoing elective surgery.
Airway closure was measured using the foreign gas bolus technique, atelectasis
was estimated by analysis of computed x-ray tomography, and ventilation-perfusion
distribution (VA/Q) was assessed by the multiple inert gas elimination technique.
The difference between closing volume and expiratory reserve volume (CV-ERV)
increased from the awake to the anaesthetized state. Linear correlations were
found between atelectasis and shunt (r = 0.68, P < 0.001), and between CV-ERV and
the amount of perfusion to poorly ventilated lung units ("low Va/Q", r = 0.57, P
= 0.001). Taken together, the amount of atelectasis and airway closure may
explain 75% of the deterioration in PaO2. There was no significant correlation
between CV-ERV and atelectasis. We conclude that in anaesthetized adults with
healthy lungs, undergoing mechanical ventilation, both airway closure and
atelectasis contributed to impairment of gas exchange. Atelectasis and airway
closure do not seem to be closely related.
PMID- 10193277
TI - Correlating fibreoptic nasotracheal endoscopy performance and psychomotor
aptitude.
AB - We have investigated the correlation between the scores attained on computerized
psychometric tests, measuring psychomotor and information processing aptitudes,
and learning fibreoptic endoscopy with the videoendoscope. Sixteen anaesthetic
trainees performed two adaptive tracking tasks (ADTRACK 2 and ADTRACK 3) and one
information management task (MAZE) from the MICROPAT testing system. They then
embarked on a standardized fibreoptic training programme during which they
performed 15 supervised fibreoptic nasotracheal intubations on anaesthetized oral
surgery patients. There was a significant correlation between the means of the 15
endoscopy times and both ADTRACK 2 (r = -0.599, P = 0.014) and ADTRACK 3 (r =
0.589, P = 0.016) scores. The correlation between the means of the 15 endoscopy
times and MAZE scores was not significant. The ratios of the mean endoscopy time
for the last seven endoscopies to the mean endoscopy time for the first seven
endoscopies were not significantly correlated with ADTRACK 2, ADTRACK 3 or MAZE
scores. Psychomotor abilities appeared to be determinants of trainees' initial
proficiency in endoscopy, but did not appear to be determinants of trainees'
rates of progress during early fibreoptic training.
PMID- 10193278
TI - Evaluation of routine tracheal extubation in children: inflating or suctioning
technique?
AB - We studied prospectively the effects of the technique of tracheal extubation on
arterial haemoglobin oxygen saturation (SpO2) in 120 ASA I-III children, mean age
5.3 (range 0.25-16.9) yr. At completion of surgery, tracheal extubation was
performed when spontaneous ventilation had resumed, children were fully awake and
SpO2 was 99-100%. Children were allocated randomly to receive a single lung
inflation manoeuvre with 100% oxygen before tracheal extubation (group I; n = 59)
or to have the tracheal tube removed while applying suction through the tube
(group S; n = 61). SpO2 was monitored during the first 5 min after tracheal
extubation in the operating room. Supplementary oxygen was given if SpO2
decreased to less than 92%. The time between tracheal extubation and decrease in
SpO2 to 92% (T92) was recorded. Children in group S required oxygen
administration more frequently after tracheal extubation than those in group I
(65.6% vs 45.8%; P = 0.04), and had a three-fold shortening of T92 (mean 25 (SD
19) s vs 85 (63) s; P = 0.0001). These effects were more pronounced in children
less than 4 yr of age compared with older children. We conclude that tracheal
extubation greatly impaired oxygenation and therefore administration of oxygen
was appropriate. This impairment was more marked when suction was used, and in
young children. Lung inflation with 100% oxygen before removal of the tracheal
tube is advised before routine tracheal extubation in children.
PMID- 10193279
TI - Non-invasive aortic blood flow measurement in infants during repair of
craniosynostosis.
AB - We have assessed the potential clinical benefit of a new echo-Doppler device
(Dynemo 3000) which provides a continuous measure of aortic blood flow (ABF)
using an aortic flowmeter and a paediatric oesophageal probe, during repair of
craniosynostosis in infants under general anaesthesia. The data recorded
included: ABFi (i = indexed to body surface area), stroke volume (SVi), systemic
vascular resistance (TSVRi), pre-ejection period (PEP), left ventricular ejection
time (LVET), mean arterial pressure (MAP), heart rate (HR) and central venous
pressure (CVP). Data were collected: before (T1) and 3 min after skin incision
(T2), at the time of maximal haemorrhage (T3) and at the end of the procedure
(T4). Twelve infants (aged 7.0 (range 6-12) months) were included. ABFi, MAP and
CVP were significantly lower at T3 compared with T1 (2.0 (0.8) vs 3.0 (0.8) litre
min-1 m-2, 46.1 (5.8) vs 65.2 (8.9) mm Hg and 2.8 (1.6) vs 5.2 (2.1) mm Hg; P <
0.05). PEP/LVET ratio was significantly lower at T2 compared with T1 (0.25 (0.05)
vs 0.30 (0.06)) and increased at T4 (0.36 (0.04); P < 0.05). These preliminary
results suggest that this non-invasive ABF echo-Doppler device may be useful for
continuous haemodynamic monitoring during a surgical procedure associated with
haemorrhage in infants.
PMID- 10193280
TI - Effect of i.v. ketamine in combination with epidural bupivacaine or epidural
morphine on postoperative pain and wound tenderness after renal surgery.
AB - We studied 60 patients undergoing operation on the kidney with combined general
and epidural anaesthesia, in a double-blind, randomized, controlled study.
Patients were allocated to receive a preoperative bolus dose of ketamine 10 mg
i.v., followed by an i.v. infusion of ketamine 10 mg h-1 for 48 h after
operation, or placebo. During the first 24 h after surgery, all patients received
4 ml h-1 of epidural bupivacaine 2.5 mg ml-1. From 24 to 48 h after operation,
patients received epidural morphine 0.2 mg h-1 preceded by a bolus dose of 2 mg.
In addition, patient-controlled analgesia (PCA) with i.v. morphine (2.5 mg,
lockout time 15 min) was offered from 0 to 48 h after operation. Patients who
received ketamine felt significantly more sedated at 0-24 h, but not at 24-48 h
after operation, compared with patients who received placebo (P = 0.002 and P =
0.127, respectively). There were no significant differences in pain (VAS) at
rest, during mobilization or cough, PCA morphine consumption, sensory block to
pinprick, pressure pain detection threshold assessed with an algometer, touch and
pain detection thresholds assessed with von Frey hairs, peak flow or side effects
other than sedation. The power of detecting a reduction in VAS scores of 20 mm in
our study was 80% at the 5% significance level. We conclude that we were unable
to demonstrate an (additive) analgesic or opioid sparing effect of ketamine 10 mg
h-1 i.v. combined with epidural bupivacaine at 0-24 h, or epidural morphine at 24
48 h after renal surgery.
PMID- 10193281
TI - Neonatal outcome and mode of delivery after epidural analgesia for labour with
ropivacaine and bupivacaine: a prospective meta-analysis.
AB - In this prospective meta-analysis, we have evaluated the effect of epidural
analgesia with ropivacaine for pain in labour on neonatal outcome and mode of
delivery compared with bupivacaine. In six randomized, double-blind studies, 403
labouring women, primigravidae and multiparae, received epidural analgesia with
ropivacaine or bupivacaine 2.5 mg ml-1. The drugs were administered as
intermittent boluses in four studies and by continuous infusion in two. Apgar
scores, neurological and adaptive capacity scores (NACS), degree of motor block
and mode of delivery were recorded. The studies were designed prospectively to
fit meta-analysis of the pooled results. Results showed similar pain relief and
consumption of the two drugs. In the vaginally delivered neonates, NACS scores
were approximately equal for both groups at 2 h, but at 24 h there were fewer
infants with NACS less than 35 in the ropivacaine compared with the bupivacaine
group (2.8% vs 7.6%; P < 0.05). Spontaneous vaginal deliveries occurred more
frequently overall with ropivacaine than with bupivacaine (58% vs 49%; P < 0.05)
and instrumental deliveries (forceps and vacuum extraction) less frequently (27%
vs 40%; P < 0.01), while the frequency of Caesarean section was similar between
groups. The intensity of motor block was lower with ropivacaine. There were no
significant differences in adverse events.
PMID- 10193282
TI - Quantitative and selective assessment of sensory block during lumbar epidural
anaesthesia with 1% or 2% lidocaine.
AB - We have examined sensory block during lumbar epidural anaesthesia using a
cutaneous current perception threshold (CPT) sensory testing device in 20
patients who received 10 ml of either 1% or 2% lidocaine (lignocaine). CPT at
2000, 250 and 5 Hz stimulation at the trigeminal (V), ninth thoracic (T9) and
second lumbar (L2) dermatomes, and dermatomal levels of block to light touch,
temperature and pinprick discrimination were measured before and every 5 min
until 60 min after epidural lidocaine. There were significant differences between
1% and 2% epidural lidocaine in all CPT at T9 and L2, in addition to maximal
cephalad spread of the three sensory modalities. After 2% lidocaine, all CPT
increased significantly at T9 and L2. In contrast, only at 250 and 5 Hz for L2
did epidural block with 1% lidocaine produce significant increases in CPT.
Maximal level of loss of touch sensation after 1% lidocaine was significantly
lower than that of cold and pinprick sensations. We conclude that the dose of
lidocaine affected intensity of sensory block during lumbar epidural anaesthesia.
In addition, differential neural block resulting from epidural anaesthesia
appeared to be associated with a differential effect on nerve fibres of different
sizes.
PMID- 10193283
TI - Incidence of bradycardia during recovery from spinal anaesthesia: influence of
patient position.
AB - We administered 0.5% plain bupivacaine 4 ml intrathecally (L2-3 or L3-4) in three
groups of 20 patients, according to the position in which they were nursed in the
post-anaesthesia care unit (PACU): supine horizontal, 30 degrees Trendelenburg or
hammock position (trunk and legs 30 degrees elevated). Patients were observed
until anaesthesia descended to less than S1. The incidence of severe bradycardia
(heart rate < 50 beat min-1) in the PACU was significantly higher in patients in
the Trendelenburg position (60%) than in the horizontal (20%, P < 0.01) or
hammock (10%, P < 0.005) position. After 90 min, following admission to the PACU,
only patients in the hammock position did not have severe bradycardia. In this
late phase, the incidence of severe bradycardia in the Trendelenburg group was
35% (P < 0.005) and 10% in patients in the supine horizontal position. In four
patients, severe bradycardia first occurred later than 90 min after admission to
the PACU. The latest occurrence of severe bradycardia was recorded 320 min after
admission to the PACU. We conclude that for recovery from spinal anaesthesia, the
Trendelenburg position should not be used and the hammock position is preferred.
PMID- 10193284
TI - Balanced pre-emptive analgesia: does it work? A double-blind, controlled study in
bilaterally symmetrical oral surgery.
AB - We studied 32 patients undergoing bilateral symmetrical lower third molar surgery
under general anaesthesia to determine if the combined effects of pre-emptive
local anaesthetic block using 0.5% bupivacaine, together with i.v. tenoxicam and
alfentanil had any benefits over postoperative administration. Patients acted as
their own controls and were allocated randomly to have surgery start on one side,
the second side always being the pre-emptive side. Difference in pain intensity
between the two sides was determined using visual analogue scales completed by
each individual at 6 h, and at 1, 3 and 6 days after operation. A long-form
McGill pain questionnaire was also used to assess difference in pain intensity
between the two sides on the morning after surgery. There was no significant
difference in pain intensity at any time after surgery. Our findings indicate
that the combined use of pre-emptive analgesia from 0.5% bupivacaine, tenoxicam
and alfentanil did not reduce postoperative pain intensity in patients undergoing
molar exodontia.
PMID- 10193285
TI - Dextromethorphan and pain after total abdominal hysterectomy.
AB - Dextromethorphan is an N-methyl-D-aspartate (NMDA) receptor antagonist which has
been shown to inhibit the development of cutaneous secondary hyperalgesia after
tissue trauma. We studied 60 ASA I-II patients undergoing total abdominal
hysterectomy in a randomized, double-blind, placebo-controlled study. Patients
received either dextromethorphan 27 mg capsules, two doses before operation and
three doses in the first 24 h after operation, or placebo. Visual analogue pain
scores (VAS) at 24 and 48 h were assessed at rest, on coughing and on sitting up,
and were not significantly different between groups. Morphine consumption from a
patient-controlled analgesia (PCA) device was also not significantly different
between groups. Evidence of secondary hyperalgesia was assessed with von Frey
hairs 10 cm above the Pfannenstiel incision. Both groups of patients exhibited
evidence of secondary hyperalgesia after 24 and 48 h but there were no
significant differences between groups. There was also no difference between
groups in VAS scores at 1 month.
PMID- 10193286
TI - Tramadol or morphine administered during operation: a study of immediate
postoperative effects after abdominal hysterectomy.
AB - Tramadol may cause awareness and EEG activation during anaesthesia. We compared
tramadol with morphine, administered during wound-closure, surmising that
tramadol may cause earlier awakening, more rapid recovery, less respiratory
depression and equivalent pain relief. Forty patients received nitrous oxide
enflurane for abdominal surgery. At wound closure, patients received tramadol 3
mg kg-1 or morphine 0.2 mg kg-1 and end-tidal enflurane concentrations were
maintained at 0.5 kPa until skin closure, whereupon anaesthesia was discontinued.
Times to spontaneous respiration, awakening and orientation were similar in the
two groups, as were blood-gas tensions, ventilatory frequency, pain scores and
incidence of nausea. Half of each group required supplementary analgesia during
their 90-min stay in the recovery room. P-deletion counts improved more rapidly
in the tramadol group. This study confirms previous reports that tramadol did not
antagonize the hypnotic effects of volatile anaesthetics. Tramadol, administered
during operation, was as effective as morphine in providing postoperative
analgesia while permitting more rapid psychomotor recovery.
PMID- 10193287
TI - Comparison of the analgesic potency of xenon and nitrous oxide in humans
evaluated by experimental pain.
AB - We have compared the analgesic potency of MAC-equivalent concentrations of xenon
(10, 20, 30 and 40%) and nitrous oxide (15, 30, 45 and 60%) in humans using a
multimodal experimental pain testing and assessment technique. We tested 12
healthy volunteers in a randomized, single-blind, crossover study. The following
experimental pain tests were used: nociceptive reflex to repeated stimuli; pain
tolerance to maximal effort tourniquet ischaemia; electrical stimulation;
mechanical pressure; and cold. Reaction time was also measured. Xenon and nitrous
oxide produced analgesia to ischaemic, electrical and mechanical stimulation, but
not to cold pain. There was no difference in MAC-equivalent concentrations of
xenon and nitrous oxide. Both increased reaction time in a similar manner. Xenon
and nitrous oxide evoked nausea and vomiting in a large number of volunteers.
PMID- 10193288
TI - Comparison of the effects of halothane, isoflurane and methoxyflurane on the
electroencephalogram of the horse.
AB - We have investigated in eight ponies the effects of three different end-tidal
concentrations of halothane, isoflurane and methoxyflurane on median (F50) and
95% spectral edge (F95) frequencies of the EEG and the second differential (DD)
of the middle latency auditory evoked potential (MLAEP). The three concentrations
of each agent were chosen to represent approximately the minimum alveolar
concentration (MAC), 1.25 MAC and 1.5 MAC for each agent. During halothane
anaesthesia, F95 decreased progressively as halothane concentration increased,
from mean 13.9 (SD 2.6) at 0.8% to 11.9 (1.1) at 1.2%. DD was lower during
anaesthesia with the highest concentration (21 (6.5)) compared with the lowest
(27.6 (11.4)). There were no significant changes in F50. During isoflurane
anaesthesia, there was a small, but significant increase in F95 between the
intermediate and highest concentrations (10.2 (1.5) to 10.8 (1.6)). There were no
changes in F50 and DD. Values of F95, F50 and DD at all isoflurane concentrations
were similar to those of halothane at the highest concentration. During
methoxyflurane anaesthesia, F95 and F50 decreased progressively as methoxyflurane
concentration was increased, from 21.3 (0.7) and 6.5 (1), respectively, at 0.26%,
to 20.1 (0.6) and 5.6 (0.8), respectively, at 0.39%. DD was lower during
anaesthesia with the highest concentration of methoxyflurane (25.7 (7.8))
compared with the lowest (39.7 (20.6)). Values of F95, F50 and DD at all
methoxyflurane concentrations were higher than those seen with halothane at the
lowest concentration. The different relative positions of the dose-response
curves for EEG and MLAEP changes compared with antinociception (MAC) changes
suggest differences in the mechanisms of action of these three agents. These
differences may explain the incomplete adherence to the Meyer-Overton rule.
PMID- 10193289
TI - Prophylactic antiemetic therapy with a combination of granisetron and
dexamethasone in patients undergoing middle ear surgery.
AB - We have compared the efficacy of granisetron in combination with dexamethasone
with each drug alone in the prevention of postoperative nausea and vomiting
(PONV) after middle ear surgery. In a randomized, double-blind study, 120
patients (85 females) received granisetron 3 mg, dexamethasone 8 mg or
granisetron 3 mg with dexamethasone 8 mg i.v. (n = 40 in each group), immediately
before induction of anaesthesia. A standardized general anaesthetic technique was
used. A complete response, defined as no PONV and no need for another rescue
antiemetic during the first 3 h after anaesthesia, was recorded in 83%, 50% and
98% of patients who had received granisetron, dexamethasone and granisetron
dexamethasone, respectively. The corresponding incidences during the next 21 h
after anaesthesia were 80%, 55% and 98% (P < 0.05; overall Fisher's exact
probability test). In summary, prophylactic use of combined granisetron and
dexamethasone was more effective than each antiemetic alone for the prevention of
PONV after middle ear surgery.
PMID- 10193290
TI - Neostigmine with glycopyrrolate does not increase the incidence or severity of
postoperative nausea and vomiting in outpatients undergoing gynaecological
laparoscopy.
AB - We studied 100 healthy women undergoing outpatient gynaecological laparoscopy in
a randomized, double-blind and placebo-controlled study to evaluate the effect of
neostigmine on postoperative nausea and vomiting (PONV). After induction of
anaesthesia with propofol, anaesthesia was maintained with sevoflurane and 66%
nitrous oxide in oxygen. Mivacurium was used for neuromuscular block. At the end
of anaesthesia, neostigmine 2.0 mg and glycopyrrolate 0.4 mg, or saline, was
given i.v. The incidence of PONV was evaluated in the postanaesthesia care unit,
on the ward and at home. The severity of nausea and vomiting, worst pain,
antiemetic and analgesic use, times to urinary voiding and home readiness were
recorded. During the first 24 h after operation, 44% of patients in the
neostigmine group and 43% in the saline group did not have PONV. We conclude that
neostigmine with glycopyrrolate did not increase the occurrence of PONV in this
patient group.
PMID- 10193291
TI - Effects of inhaled oxygen concentration on fat metabolism during propofol
infusion in rabbits.
AB - We have investigated the effect of inhaled oxygen tension on lipid metabolism
during propofol infusion. Propofol is supplied as a lipid emulsion containing 10%
soybean oil, which is rich in triglycerides (TG). Infused TG are metabolized via
three pathways in the liver cell; Krebs cycle, ketogenesis and release as very
low density lipoproteins (VLDL) into the blood. For this reason, we measured TG
and the products of the three pathways; carbon dioxide, ketone bodies and VLDL.
Thirty-two rabbits were anaesthetized under four different conditions: propofol
under hyperoxia, normoxia, hypoxia and isoflurane anaesthesia under hyperoxia.
Our results indicated that hyperoxia produced more ketone bodies, normoxia more
PaCO2 and hypoxia more free fatty acids (FFA) and TG compared with the other
propofol infusion groups. We conclude that hyperoxia during propofol infusion
facilitated fat metabolism through ketogenesis, while normoxia did so via the
Krebs cycle. Also, hypoxia suppressed utilization of TG and VLDL production in
the liver.
PMID- 10193292
TI - Thiopental and propofol impair relaxation produced by ATP-sensitive potassium
channel openers in the rat aorta.
AB - ATP-sensitive potassium channel openers are used as vasodilators in the treatment
of cardiovascular disorders. The effects of i.v. anaesthetics on arterial
relaxation induced by ATP-sensitive potassium channel openers have not been
studied. Therefore, in this study, we have examined if thiopental (thiopentone)
and propofol affect the vascular response to the ATP-sensitive potassium channel
openers, cromakalim and pinacidil, in the isolated rat aorta. Rings of rat
thoracic aortas without endothelium were suspended for isometric force recording.
Concentration-response curves were obtained in a cumulative manner. During
submaximal contractions with phenylephrine 0.3 mumol litre-1, relaxation after
cromakalim 0.1-30 mumol litre-1, pinacidil 0.1-30 mumol litre-1 and papaverine
0.1-300 mumol litre-1 was demonstrated. Thiopental 30-300 mumol litre-1, propofol
10-100 mumol litre-1, 10% Intralipid 45 microliters or glibenclamide 5 mumol
litre-1 were applied 15 min before addition of phenylephrine. During contractions
with phenylephrine, cromakalim and pinacidil induced concentration-dependent
relaxation. A selective ATP-sensitive potassium channel antagonist, glibenclamide
5 mumol litre-1, abolished this relaxation, whereas it did not affect relaxation
produced by papaverine. Thiopental concentrations > 30 mumol litre-1
significantly impaired relaxation produced by cromakalim or pinacidil. Propofol
concentrations > 10 mumol litre-1 also significantly reduced relaxation produced
by cromakalim or pinacidil, whereas Intralipid was ineffective. Thiopental 300
mumol litre-1 and propofol 100 mumol litre-1 did not alter relaxation produced by
papaverine. These results suggest that the i.v. anaesthetics, thiopental and
propofol, impaired vasodilatation mediated by ATP-sensitive potassium channels in
vascular smooth muscle cells.
PMID- 10193293
TI - Evoked responses in anaesthesia.
PMID- 10193294
TI - A single dose of milrinone facilitates separation from cardiopulmonary bypass in
patients with pre-existing left ventricular dysfunction.
AB - Milrinone is used during cardiac surgery to facilitate separation from
cardiopulmonary bypass (CPB) and/or to treat myocardial dysfunction in the post
bypass period. We have demonstrated, in patients with preoperative depression of
systolic function undergoing aorto-coronary artery bypass surgery, sustained
improvement in cardiac function after a single loading dose of milrinone 50
micrograms kg-1, administered at the end of bypass, thus significantly decreasing
the need for beta-agonist therapy.
PMID- 10193295
TI - Effect of remifentanil on the auditory evoked response and haemodynamic changes
after intubation and surgical incision.
AB - We have observed the effect of intubation and incision, as measured by the
auditory evoked response (AER) and haemodynamic variables, in 12 patients
undergoing hernia repair or varicose vein surgery who received remifentanil as
part of either an inhaled anaesthetic technique using isoflurane or as part of a
total i.v. technique using propofol. Anaesthesia was induced with remifentanil 1
microgram kg-1 and propofol, neuromuscular block was achieved with atracurium 0.6
mg kg-1 before intubation, and anaesthesia was maintained with a continuous
infusion of remifentanil in combination with either a continuous infusion of
propofol or inhaled isoflurane. The AER and haemodynamic variables were measured
before and after intubation and incision. The effects of intubation and incision
on the AER and haemodynamic variables were not significantly different between
the remifentanil-propofol and remifentanil-isoflurane groups. However, the study
had a low power for this comparison. When the data for the two anaesthetic
combinations were pooled, the only significant effects were increases in
diastolic arterial pressure and heart rate immediately after intubation; these
were not seen 5 min after intubation. There were no cardiovascular responses to
incision. There were no significant changes in the AER after intubation or
incision.
PMID- 10193296
TI - Vital capacity and tidal volume preoxygenation with a mouthpiece.
AB - We have measured oxygen wash-in in 20 volunteers undergoing preoxygenation with a
face mask, mouthpiece alone and a mouthpiece with a noseclip, in a crossover
study. Tidal volume breathing and maximal deep breath techniques were studied
with each type of equipment. When tidal volume breathing was used, the face mask
and mouthpiece with noseclip were comparable, but the mouthpiece alone achieved a
lower end-expiratory oxygen concentration than the two other methods after 3 min
(P < 0.001 and P < 0.01), and after 5 min (P < 0.05 in each case). Conversely,
during preoxygenation with vital capacity breaths, the mouthpiece and mouthpiece
with noseclip were comparable, and both were more effective than the face mask (P
< 0.001). In a second study, 20 patients who had undergone preoxygenation before
induction of anaesthesia were asked later if they would have preferred the face
mask or mouthpiece for this procedure. Significantly more patients (14 of 18 who
expressed a preference) favoured the mouthpiece (P < 0.05; confidence limits 0.56
0.92).
PMID- 10193297
TI - Anaesthesia for caesarean section in the presence of severe primary pulmonary
hypertension.
AB - We describe the case of a pregnant woman, 35 weeks' gestation, with primary
pulmonary hypertension and coarctation of the aorta requiring emergency Caesarean
section under general anaesthesia. The patient had a pulmonary artery catheter
inserted before operation which revealed pulmonary artery pressures in excess of
80/40 mm Hg. These were lowered using an infusion of glyceryl trinitrate. After
delivery of the baby and administration of oxytocin, pulmonary artery pressures
were more difficult to control. An infusion of prostacyclin was substituted which
stabilized pulmonary pressures. After operation, she was transferred to the
intensive care unit where prostacyclin was administered by an "aerosolized"
route. Her trachea was extubated after 48 h and she made an uneventful recovery.
PMID- 10193298
TI - Inadvertent inhalation anaesthesia during surgery under retrobulbar eye block.
AB - I describe a case of inadvertent inhalation anaesthesia during surgery under
retrobulbar anaesthesia and its management. Some of the hazards of supplementary
oxygen delivery during monitored anaesthetic care and the actions taken to
prevent this mishap recurring are discussed.
PMID- 10193299
TI - Autoclaving impairs the connector-tube bond of the laryngeal mask airway but not
its airtightness.
AB - The general-purpose laryngeal mask airway (LMA) is re-usable when undamaged, and
cleaned and autoclaved correctly. We had found weakening of the silicone adhesive
that bonds the connector of the LMA to the tube. We report that repeated
autoclaving damaged the adhesive such that the connector could be rotated in the
tube after the 12th autoclave cycle in almost all of the LMA tested. The damage
to the adhesive did not affect the airtightness of the junction, which appears to
be maintained by the material properties of the connector and tube and by the
shape of the join.
PMID- 10193300
TI - Rapid intraoperative reduction of intracranial pressure with thiopentone. 1973.
PMID- 10193301
TI - Complication of the transtracheal catheter.
PMID- 10193302
TI - Blood transfusion for caesarean section.
PMID- 10193303
TI - Postoperative hypoxaemia.
PMID- 10193304
TI - Accidental i.v. injection of local anaesthetic.
PMID- 10193306
TI - Accidental i.v. injection of local anaesthetic.
PMID- 10193309
TI - The vascular endothelial growth factor family; proteins which guide the
development of the vasculature.
AB - The development of the vascular tree during embryogenesis involves
vasculogenesis, angiogenesis and tissue-specific differentiation of endothelium
which gives rise to many different vessel types. These processes are
physiologically complex and are therefore difficult to study in vitro. However,
the discovery of endothelial cell-specific receptors and cognate ligands has led
to the generation of transgenic and knockout mouse models which have shed light
on the molecular mechanisms that regulate the development of blood and lymphatic
vessels during embryogenesis. Such mouse models have demonstrated that members of
the vascular endothelial growth factor (VEGF) family of proteins and the VEGF
receptors are critical regulators of vasculogenesis, angiogenesis and endothelial
cell differentiation. The availability of purified VEGF family members and of
inhibitors of these growth factors may provide a means to modulate blood vessel
growth for the treatment of cancer, retinopathies and diseases of ischemia.
PMID- 10193310
TI - Hepatocyte growth factor in transgenic mice.
AB - In order to clarify the function of hepatocyte growth factor (HGF) in vivo, we
have developed transgenic mice expressing HGF in the liver. The bromodeoxyuridine
labelling indices in livers from HGF transgenic mice were doubled, compared to
those from wild type mice. Livers of HGF transgenic mice expressed high levels of
c-myc, which was the consequence of increased transcription rates through the c
myc promoter. After 70% partial hepatectomy, the livers of HGF transgenic mice
recovered in half the time needed for their normal siblings. Since we found that
HGF inhibits growth of hepatocellular carcinoma (HCC) cells in vitro, we have
made two kinds of double transgenic mice: HGF/TGF alpha and HGF/c-myc mice. The
double transgenic mice expressing both HGF and TGF alpha had lower tumour yields,
compared to TGF alpha transgenic mice. The HGF/c-myc double transgenic mice had a
lower incidence of hepatocellular adenoma (HCA) and HCC in comparison with c-myc
transgenic mice. In HGF/c-myc mice, there were more apoptotic cells and less
mitotic cells than c-myc transgenic mice. These data indicate that HGF inhibits
growth and occurrence of HCC in vivo. We also found that HGF protects liver from
D-galactosamine (D-GalN)-induced injury. Hepatic prostaglandin E 2 (PGE2)
contents in HGF transgenic mice were much higher than those in wild type mice,
and were associated with hepatic HGF contents. An anti-HGF antibody inhibits
production of PGE2 in liver after D-GalN administration. These data suggest that
HGF protects liver from D-GalN-induced injury through increased liver PGE2
production. The data obtained from HGF transgenic mice suggests the possibility
that HGF could be applicable for therapy of human liver diseases in the future.
PMID- 10193311
TI - Hepatitis B virus (HBV)-transgenic mice as an investigative tool to study
immunopathology during HBV infection.
AB - An overview is given regarding the use of hepatitis B virus (HBV) transgenic mice
as an animal model of the HBV-carrier state. Initially, we show how HBV
transgenic mice have contributed insights into the immunopathobiological
processes during HBV infection and later, we show how this new information from
the experiments with HBV-transgenic mice could be used to develop new methods to
combat HBV infection. By microinjecting the full or selected parts of the HBV
genome into the fertilized eggs of inbred mice, different laboratories have
developed different lines of HBV-transgenic mice, which express products of the
HBV genome and also show signs of HBV replication. Studies in HBV-transgenic mice
have provided insights into the process of destruction of hepatocytes, the
critical role of cytokines in controlling HBV replication and gene expression,
mechanisms underlying the immune response defect in chronic HBV-carriers and the
critical role of antigen presenting cells (APC), especially that of antigen
presenting dendritic cells in persistent HBV infection. All this new information
has given us a better understanding about HBV immunopathobiology, and has led to
the development of new therapeutic approaches to combat HBV infection.
PMID- 10193312
TI - Origin of acinar cell regeneration after atrophy of the rat parotid induced by
duct obstruction.
AB - Acinar cell regeneration in the rat parotid gland after atrophy induced by a one
week period of duct obstruction was examined using histology,
immunohistochemistry and transmission electron microscopy (TEM). For
immunohistochemistry, antibodies to 5-bromo-2'-deoxyuridine (BrdU), injected one
hour before tissue collection, and cytokeratin were employed. When clips were
removed from the duct, only ductal epithelial cells remained; all acinar cells
had been deleted. Some duct cells were BrdU positive. After three days, newly
formed acini comprising immature acinar cells had appeared; many of the cells
were BrdU positive and mitotic figures were readily identified. Thereafter
progressive acinar cell maturation and proliferation occurred, parotid gland
weight returning to control levels by 7 days. Peak BrdU labelling indices for
duct and acinar cells were on days 0 and 4, respectively. By TEM, cytoplasmic
organelles in epithelial cells of transitional duct-acinar structures seen at 2
days were poorly developed. Immature acinar cells seen on day 3 contained zymogen
granules and had increased endoplasmic reticulum and mitochondria. By day 5,
maturing acinar cells had abundant endoplasmic reticulum and zymogen granules,
resembling acinar cells in control glands. These observations indicated origin of
acinar cell precursors from duct cells during regeneration of the acinar cell
free atrophic gland. Subsequent expansion of the acinar cell population was
dependent on maturation and proliferation of these newly-formed cells.
PMID- 10193313
TI - Apoptosis is a pathway responsible for the resolution of endotoxin-induced
alveolar type II cell hyperplasia in the rat.
AB - Previous studies showed that intratracheal instillation of endotoxin induces
transient type II cell hyperplasia in the rat lung and described some of the
mechanisms involved in the proliferative response of type II cells. The purpose
of the present study was to investigate how long the type II cell hyperplasia
persists and how it is resolved. The portion of epithelial cells in hyperplastic
lesions of the rat lung expressing cyclin D1, an indicator for cells in the G1
phase of the cell cycle, was greatest at 3 d post instillation and decreased
after 4 and 6 d. The fate of the proliferating epithelial cells was traced by
injecting the rats with 5-bromo-2' deoxy uridine (BrdU) 2 d post instillation,
the peak time point for maximum incorporation of BrdU. Exfoliated BrdU-positive
epithelial cells were detected in the alveolar spaces in tissue sections from
rats 4, 5, and 6 d post instillation. BrdU-positive epithelial cells showed
flattened nuclei at 6 and 10 d post instillation. Expression of the 116 kD
poly(ADP-ribose) polymerase (PARP) was low in type II cells from control rats,
and was increased at 3, 4, and 6 d post instillation. In cells obtained by
lavage, only a 35 kD cleavage product of PARP was detected, which is an indicator
of necrotic cell death. In isolated type II cells from rats 3, 4, and 6 d post
endotoxin instillation, progressive cleavage of the PARP to its 89 kD residual
fragment was detected, which is a direct evidence for the activation of caspases.
Furthermore, apoptotic epithelial cells with condensed nuclei were identified by
electron microscopy in rats 4 d post instillation. These results indicate that
apoptosis is an additional mechanism for the resolution of endotoxin-induced lung
epithelial hyperplasias.
PMID- 10193314
TI - Interferon-gamma plays a role in pancreatic islet-cell destruction of reovirus
type 2-induced diabetes-like syndrome in DBA/1 suckling mice.
AB - Reovirus type 2 (Reo-2) infection in DBA/1 suckling mice causes insulitis, which
leads to pancreatic islet-cell destruction, resulting in a diabetes-like
syndrome. T-helper (Th) 1 cytokines are thought to play a key role in islet
inflammation in insulin-dependent diabetes mellitus. We examined this hypothesis
in the Reo-2-induced diabetes-like syndrome. We used reverse transcriptase
polymerase chain reaction (PCR) and quantitative PCR techniques to examine mRNA
expression of interferon (IFN)-gamma (Th1 type cytokine), and interleukin (IL)-4
(Th2 type cytokine) in splenic cells. We observed that in Reo-2 infected mice the
level of IFN-gamma expression increases with the development of insulitis,
whereas expression of message for IL-4 is minimal to detectable with the immuno
inflammatory process 10 days after infection. The treatment of monoclonal
antibody (mAb) against mouse IFN-gamma during the expansion phase of insulitis (5
9 days after infection) inhibited the development of insulitis and the elevation
of blood glucose concentrations in a dose dependent manner. Furthermore altered
CD4+/CD8+ cell ratio compared with uninfected mice in the splenic cells by the
infection was recovered to the ratio of uninfected mice by the treatment of mAb
against mouse IFN-gamma, suggesting normalization of T cell balance in immune
system. These results suggest that Reo-2-triggered autoimmune insulitis may be
mediated by Th1 lymphocytes and IFN-gamma may play a role in islet inflammation
leading to islet cell destruction.
PMID- 10193315
TI - Collagen synthesis in rat skin and ileum fibroblasts is affected differently by
diabetes-related factors.
AB - Untreated diabetes reduces wound strength: a concomitant reduction in collagen
deposition has been found in cutaneous wounds but not in intestinal anastomoses.
This raises the question if collagen synthesis in fibroblasts from skin and
intestine reacts differently to the diabetic state. Fibroblast lines were
established from healthy rat skin and ileum. Diabetic rat serum was collected
from hyperglycaemic rats 3 days after intravenous injection of streptozotocin
(200 mg/kg). Fibroblast cultures were grown to confluency in foetal calf serum
and maintained in various concentrations of glucose, insulin, normal or diabetic
rat serum. Collagen synthesis was measured by incorporation of [3H]-proline into
Collagenase-Digestible-Protein. Collagen synthesis in fibroblasts from both skin
and ileum was not affected by increasing glucose concentrations. Insulin strongly
and specifically stimulated collagen synthesis in skin fibroblasts whereas in
ileum fibroblasts only a nonspecific increase of total protein synthesis was
observed. In skin fibroblasts, diabetic rat serum stimulated collagen synthesis
to a significantly lesser extent than normal rat serum, whereas in ileum
fibroblasts stimulation by serum was far less explicit and no difference was
observed between normal and diabetic serum. The fact that ileum fibroblasts
respond less strongly to culture in diabetic serum than skin fibroblasts may
explain our prior finding that would collagen accumulation in intestinal
anastomoses is virtually unaffected during diabetes and supports the existence of
tissue-specific healing responses.
PMID- 10193316
TI - The bcl-2 knockout mouse exhibits marked changes in osteoblast phenotype and
collagen deposition in bone as well as a mild growth plate phenotype.
AB - Histological examination of long bones from 1-day-old bcl-2 knockout and age
matched control mice revealed no obvious differences in length of bone, growth
plate architecture or stage of endochondral ossification. In 35-day-old bcl-2
knockout mice that are growth retarded or 'dwarfed'. the proliferative zone of
the growth plate appeared slightly thinner and the secondary centres of
ossification less well developed than their age-matched wild-type controls. The
most marked histological effects of bcl-2 ablation were on osteoblasts and bone.
35-day-old knockout mouse bones exhibited far greater numbers of osteoblasts than
controls and the osteoblasts had a cuboidal phenotype in comparison with the
normal flattened cell appearance. In addition, the collagen deposited by the
osteoblasts in the bcl-2 knockout mouse bone was disorganized in comparison with
control tissue and had a pseudo-woven appearance. The results suggest an
important role for Bcl-2 in controlling osteoblast phenotype and bone deposition
in vivo.
PMID- 10193317
TI - Chlamydia pneumoniae in arteries: the facts, their interpretation, and future
studies.
PMID- 10193318
TI - De novo expression of CD44 in prostate carcinoma is correlated with systemic
dissemination of prostate cancer.
AB - AIMS: To evaluate the role of CD44 in early steps in the development of prostate
cancer, and to assess the biological significance of preneoplastic lesions in
prostate cancer. METHODS: 38 patients with clinically localised prostate cancer
were studied. The standard form of CD44 (CD44H) and v6 isoform expressions were
semiquantitatively evaluated on paraffin embedded tumour tissue by
immunohistochemistry. Disseminated prostatic cells were detected by prostate
specific membrane antigen reverse transcriptase polymerase chain reaction in the
blood of each patient before radical prostatectomy. RESULTS: In normal or benign
prostate glands, only basal cells showed CD44H and v6 labelling. Fourteen of the
38 prostate cancers (37%) had CD44H membranous staining of prostatic tumour
cells. In 18 patients (47%), circulating prostatic cells were detected in blood
before surgery. Although no correlation between the expression of CD44 and the
Gleason score or staging was observed, a significant correlation was found
between the expression of CD44H by tumour cells and prostatic cell blood
dissemination (p = 0.04). In 28 cases, foci of prostatic intraepithelial
neoplasia were observed, and nine had CD44H immunostaining. CONCLUSIONS: De novo
expression of CD44 by prostatic tumour cells is associated with systemic
dissemination of prostate cells independently of pathological criteria.
PMID- 10193319
TI - In situ hybridisation and direct fluorescence antibodies for the detection of
Chlamydia trachomatis in synovial tissue from patients with reactive arthritis.
AB - BACKGROUND: Chlamydia trachomatis is associated with Reiter's syndrome and
reactive arthritis but the form in which the organism survives in synovial cells
is unclear. AIM: To compare in situ hybridisation with direct fluorescence in the
detection of inapparent chlamydial infection in synovial tissue. METHODS:
Synovial tissue from four patients with reactive arthritis patients was examined
using biotin labelled probes for chlamydial DNA and fluorescein isothiocyanate
(FITC) labelled monoclonal antibodies against the major outer membrane protein.
RESULTS: In two of the four patients, evidence of chlamydial infections was
detected by in situ hybridisation in parallel sections but not with FITC labelled
monoclonal antibodies. CONCLUSIONS: Detection of chlamydial DNA by in situ DNA
hybridisation may be a better way to identify chlamydial infection in synovial
tissue than phenotype targeting with FITC conjugated antibodies, which is used as
a standard procedure for screening clinical specimens for chlamydia.
PMID- 10193320
TI - Detection of cytomegalovirus in upper gastrointestinal biopsies from heart
transplant recipients: comparison of light microscopy, immunocytochemistry, in
situ hybridisation, and nested PCR.
AB - AIM: To establish the diagnostic value of in situ hybridisation and the nested
polymerase chain reaction (PCR) in detecting clinically relevant cytomegalovirus
(CMV) infection in upper gastrointestinal biopsies from heart transplant
patients. METHODS: Test sensitivity and specificity for detection of CMV early
gene RNA by in situ hybridisation and CMV intermediate early gene by PCR were
established and then compared with haematoxylin and eosin (H&E) and
immunocytochemical detection of CMV in order to establish the best pathological
diagnostic approach. All investigations were carried out on formalin fixed,
paraffin embedded tissue. RESULTS: Nested PCR had the highest test sensitivity,
followed by in situ hybridisation and immunocytochemistry with the same
sensitivity; H&E had the lowest. H&E and immunocytochemistry were the most
specific but both had a significant false negative rate which was less of a
problem with PCR. However, PCR gave no other diagnostic information, and in situ
hybridisation was no better than immunocytochemistry. Both in situ hybridisation
and PCR were technically complex and more expensive. CONCLUSIONS: H&E and
immunocytochemistry represent the best initial screen for CMV and other diseases
in upper gastrointestinal biopsies from heart transplant patients. If H&E and
immunocytochemistry were negative, nested PCR could significantly increase the
diagnostic yield of clinically relevant CMV infection. In situ hybridisation
appeared to have no advantages and some drawbacks compared with
immunocytochemistry and PCR.
PMID- 10193321
TI - Chlamydia pneumoniae in atheroma: consideration of criteria for causality.
AB - AIMS: (1) To seek evidence of the existence of Chlamydia pneumoniae in a spectrum
of atheromatous lesions in different types of arteries from individuals of
different ages, using a polymerase chain reaction (PCR) assay supported by
electron microscopy and immunocytochemistry; (2) to use electron microscopy to
examine interactions between C pneumoniae and the cells present in the arterial
tissue; (3) to assess the extent to which the data fulfil the criteria for
causality. METHODS: At necropsy examination, 35 arterial specimens were taken
from 25 subjects. The grade of atheroma was determined macroscopically and
microscopically and the tissues coded and examined by the three techniques.
RESULTS: Of the 35 specimens, 24 had macroscopic or microscopic atheromatous
lesions of varying degree. Twenty two of the 35 specimens were examined by
electron microscopy, C pneumoniae-like bodies being found in 11 (50%); seven
specimens were examined by the immunocytochemical method, positive staining being
detected in three; and all specimens were examined by the PCR technique, 15 (43%)
being PCR positive. Overall, of the 24 specimens with lesions, 17 (71%) were
positive by at least one of the three tests, whereas of the 11 specimens without
lesions, only one was positive. The positive specimens comprised 10 of 19 aortas,
three of six iliac arteries, and one coronary and one pulmonary artery. C
pneumoniae was detected in four of six specimens in which there were early
changes and in a 20 year old subject. Concerning the 25 subjects, of 17 who had
atheromatous arteries, 14 (82%) were C pneumoniae positive and of the eight who
had normal arteries, none was positive. CONCLUSIONS: There is a strong
correlation between C pneumoniae and arterial atheromatous lesions. The organism
may contribute to the disease process by damaging smooth muscle cells.
PMID- 10193322
TI - Retinoblastoma (RB1) gene product expression in breast carcinoma. Correlation
with Ki-67 growth fraction and biopathological profile.
AB - AIMS: To investigate the expression of retinoblastoma protein (pRb) in invasive
breast tumours and compare its expression with the major biopathological
prognostic indicators to identify more aggressive subgroups. MATERIAL: Archival
paraffin embedded tissues from 153 consecutive primary breast carcinomas.
METHODS: pRb, Ki-67, and oestrogen receptor/progesterone receptor proteins were
identified by immunohistochemistry and score values were recorded by image
cytometric analysis; p53 and EGFr expression was also evaluated. RESULTS: pRb
scores correlated strongly with proliferation activity as determined by Ki-67
staining. Positive relations were also observed between pRb scores, tumour size,
nuclear and histological grade, and oestrogen receptor/progesterone receptor
content, while abnormal p53 accumulation was not associated with pRb expression.
Among the high proliferating carcinomas it was possible to identify 13 cases with
loss of pRb expression. CONCLUSIONS: pRb expression paralleled proliferative
activity in the majority of breast carcinomas examined, suggesting that in these
cases the protein behaves normally in regulating the cell cycle. Conversely in
cases with loss of pRb immunostaining, the combined expression of specific highly
aggressive factors (EGFr and p53 expression, oestrogen receptor/progesterone
receptor negative status, and high K67) seems to characterise a more aggressive
phenotype showing growth advantage and cellular "progression" rather than
significant nodal involvement.
PMID- 10193323
TI - Increased sialylation of oligosaccharides on IgG paraproteins--a potential new
tumour marker in multiple myeloma.
AB - AIMS: To investigate whether changes in carbohydrate structure of IgG are related
to malignancy and stage of disease in myeloma and monoclonal gammopathy of
uncertain significance (MGUS). METHODS: 61 patients were studied at diagnosis: 14
with MGUS, nine with stage I multiple myeloma, 11 with stage II, 21 with stage
III, and five with solitary plasmacytoma. IgG was extracted from serum by protein
G affinity chromatography. Oligosaccharides were cleaved from the protein
backbone enzymatically by N-glycosidase F. Oligosaccharide analysis was performed
by high pressure anion exchange chromatography with pulsed electrochemical
detection (HPAE-PED). RESULTS: Up to 15 oligosaccharide peaks were identified in
three major fractions: neutral, monosialylated, and disialylated. Patients with
myeloma showed an increase in the proportion of sialylated oligosaccharides in
comparison with patients with MGUS. The ratio of neutral to sialylated
oligosaccharides (N:S) was reduced at all stages of myeloma compared with MGUS:
MGUS, 11.35; myeloma stage I, 7.6 (p = 0.047); stage II, 5.20 (p = 0.035); stage
III, 3.60 (p = 0.0002); plasmacytoma, 7.5 (p = 0.046). The N:S ratio was
independent of paraprotein concentration (r = 0.05). CONCLUSIONS: The ratio of
neutral to sialylated oligosaccharides may act as a new marker of malignancy in
IgG paraproteinaemia and warrants further investigation.
PMID- 10193324
TI - Study of the cell biology and biochemistry of cherubism.
AB - AIMS: To establish whether the multinucleate cells in lesions of patients with
cherubism are also osteoclasts and if this is the case whether they were
responsive to calcitonin; to carry out cytogenetic studies on two members of the
same family affected by cherubism in an attempt to identify any major chromosomal
defects; and to perform an in-depth modern biochemical study of four children in
the same family. SUBJECTS AND METHODS: Four related children with cherubism were
studied. Tissue taken from one of the children at elective decompression of an
optic nerve was submitted to in vitro bone resorption studies. Cytogenetic
studies were done on two of the children and biochemical studies on all four.
RESULTS: The multinucleate cells in the cherubic lesions were shown to be
osteoclasts since they synthesised tartrate resistant acid phosphatase, expressed
the vitronectin receptor, and resorbed bone. Bone resorption by the cultured
multinucleate cells was significantly inhibited by calcitonin. High resolution
cytogenetic studies failed to detect any chromosomal abnormalities in two
children with cherubism. The biochemistry profile of all four children with
cherubism showed that serum calcium, parathyroid hormone, parathyroid related
hormone, calcitonin, and alkaline phosphatase were within normal levels. Urine
analysis of pyridinium and deoxypyridinium cross links, hydroxyproline, and
calcium in relation to urine creatinine were measured to assess bone resorption
in these children, and the values were at the upper end of the normal range in
all four. CONCLUSIONS: Further studies are required to determine whether
calcitonin treatment will control this grossly deforming disease until the time
when the physiological changes that occur at puberty rectify the pathology. It is
not recommended that biochemical markers of bone resorption are used in isolation
to monitor the activity of cherubism in individuals because the results are based
on a small number of children and because of reports of marked interindividual
variation in the levels of these markers, particularly in children.
PMID- 10193325
TI - Intraepithelial haemorrhage of the oesophagus: a terminal event in haematological
disorders.
AB - AIMS: To investigate the clinicopathological findings in cases with
intraepithelial haemorrhage of the oesophagus (IHO). METHODS: Necropsy records
and the histopathology findings in the oesophagus were reviewed for the period
1990 to 1995. Six cases (0.7%) of IHO were found among 919 necropsy cases.
Clinical records of these patients and gross and microscopic slides were reviewed
in detail. RESULTS: The ages of the IHO cases ranged from 42 to 82 years (average
68 years), with a male to female ratio of 1:2. All cases had underlying
haematological disorders with thrombocytopenia, but disseminated intravascular
coagulation was not evident in any case. Macroscopically, solitary (two cases) or
multiple (four cases) haemorrhagic lesions ranging from 6 to 79 mm in size were
identified within the distal oesophagus. Microscopically, there was no
inflammatory infiltration, destruction of red blood cells, or submucosal scar
formation. CONCLUSIONS: IHO seems to occur shortly before death as a terminal
event in haematological disorders. Based on these observations, the term
"terminal IHO" can be suggested for this type of oesophageal lesion.
PMID- 10193326
TI - Schwannoma with features mimicking neuroblastoma: report of two cases with
immunohistochemical and ultrastructural findings.
AB - OBJECTIVE: A study of two cases of a rare variant of benign schwannoma showing
areas mimicking neuroblastoma/peripheral primitive neuroectodermal tumour (PNET).
METHODS: Sections of formalin fixed, paraffin embedded specimens were studied by
tinctorial stains and immunohistochemistry, and the tissue retrieved from
formalin was examined by electronmicroscopy in one case. RESULTS: The tumours
were small and subcutaneous. Both showed features of benign schwannoma; one had a
multinodular plexiform pattern. In addition, rosette-like structures consisting
of collagenous cores surrounded by small round cells or slightly larger
epithelioid cells were present. Tumour cells were positive for S100 protein,
Leu7, and in one case GFAP, but were negative for neurofilament protein,
synaptophysin, and MIC2. Type IV collagen surrounded individual cells.
Electronmicroscopy in case 2 confirmed schwannian features (lamina, processes)
and failed to show features of neuroblastoma (neuroendocrine granules).
CONCLUSIONS: Benign schwannomas may contain rosette-like structures mimicking
neuroblastoma/PNET. The techniques used confirmed schwannian differentiation only
and eliminated neuroblastoma/PNET. These uncommon variants should be recognised
by practising histopathologists to avoid erroneous diagnoses and inappropriate
treatment.
PMID- 10193327
TI - How to improve low lymph node recovery rates from axillary clearance specimens of
breast cancer. A short-term audit.
AB - AIM: To implement an audit scheme to increase the lymph node yield from axillary
clearance specimens. METHODS: Two pathologists cut up each specimen after
weighing it. The number of nodes and the dimensions of the largest and smallest
nodes were recorded, together with the number of non-lymph node structures
recovered. Fifty consecutive audited cases were compared with 50 consecutive
cases assessed before the audit process. RESULTS: It proved possible to increase
the median number of lymph nodes from 10 to 22. There was an obvious learning
period, during which the number of nodes recovered during the second
pathologist's cut-up gradually decreased, while the total number remained
relatively constant. The increase in lymph node yield resulted from the recovery
of smaller nodes. The identification of lymph nodes also improved, and fewer non
lymph node structures were recovered by the end of the study. CONCLUSIONS: Such
an audit scheme can be recommended for all institutions where the lymph node
yield of axillary clearance specimens seems suboptimal. The relevance of
recovering more nodes remains to be determined; from this small series, it seems
to have no clinical impact.
PMID- 10193328
TI - Improving the quality of perinatal and infant necropsy examinations: a follow up
study.
AB - AIM: To compare the quality of perinatal and infant necropsy examinations in 1996
with those performed in 1993. METHODS: Cohort analysis, with data from the All
Wales Perinatal Survey, of 1027 deaths (540 in 1993; 487 in 1996) of babies
between 20 weeks' gestation and one year of age. The quality of the necropsy was
assessed by scoring aspects identified as being part of the investigation.
RESULTS: Necropsy was performed in 335 cases (62%) in 1993 and in 320 cases (66%)
in 1996. The proportion done in a regional centre increased significantly from
39% (131/335) in 1993 to 76% (243/320) in 1996 (p < 0.0001). The quality of
necropsy was above the minimum standard in 54% of cases in 1993 (171/314)
compared with 93% in 1996 (289/312) (p < 0.0001). Improvement occurred in all
categories. For stillbirths, 35% (46/133) were above the minimum standard in 1993
compared with 90% (104/116) in 1996 (p < 0.0001); for cases not classified as
sudden unexpected death in infancy (SUDI), the improvement was from 62% in 1993
(40/65) to 97% in 1996 (73/75) (p < 0.0001); and for SUDI cases, the improvement
was from 32% in 1993 (10/31) to 91% in 1996 (21/23) (p < 0.0001). The quality of
both non-regional and regional necropsies improved. For non-regional cases, the
score was above the minimum standard in 28% (51/183) in 1993 compared with 69%
(52/75) in 1996 (p < 0.0001); for regional cases it improved from 92% (120/131)
in 1993 to 100% (237/237) in 1996 (p < 0.0001). CONCLUSIONS: The quality of
perinatal and infant necropsies improved considerably between 1993 and 1996,
reflecting better awareness of the importance of good quality examination and an
increase in referrals to paediatric centres.
PMID- 10193329
TI - An immunoblotting procedure comprising O = 9,12 and H = d antigens as an
alternative to the Widal agglutination assay.
AB - AIMS: To compare the established Widal agglutination assay with an immunoblotting
procedure. METHODS: 110 sera were used to compare the established Widal
agglutination assay with an immunoblotting procedure incorporating
lipopolysaccharide (LPS) (O = 9,12) and flagellar (H = d) antigens. RESULTS:
Antibodies to the LPS antigens were detected in 18 sera by the Widal assay and in
37 by immunoblotting. Antibodies to the flagellar antigens were detected in 27
sera by Widal assay and in 25 by immunoblotting. CONCLUSIONS: An immunoblotting
procedure incorporating O = 9,12 LPS and H = d flagellar antigens was rapid and
more sensitive than the established Widal agglutination assay for providing
evidence of infection with S typhi.
PMID- 10193330
TI - Immunocytochemical detection of Candida albicans in formalin fixed, paraffin
embedded material.
AB - AIM: To assess the ability of the commercially available monoclonal antibody 1B12
(BioGenex, San Ramon, USA) to identify C albicans in formalin fixed, paraffin wax
embedded material (FFPE). METHODS: Broth cultures of 20 strains of seven Candida
species were resuspended in 4% agarose blocks, fixed in formalin for 24 hours,
and embedded in paraffin wax. In addition, 16 blocks of FFPE tissue known to
contain periodic acid-Schiff positive fungal hyphae were examined. Antigen
retrieval involved microwave treatment of specimens in citrate buffer (0.01 M; pH
6.5) before addition of 1B12 antibody for 24 hours. Bound antibody was
subsequently detected using a biotinylated link antibody and a peroxidase
conjugated streptavidin. RESULTS: Only C albicans strains were 1B12 positive in
the agarose blocks. All FFPE tissue blocks were found to contain 1B12 positive
hyphal structures, indicating the presence of C albicans. CONCLUSIONS: The
ability to identify candida organisms penetrating the lesional tissue in cases of
chronic hyperplastic candidosis will help to clarify the role of individual
Candida spp in this important form of oral candidosis.
PMID- 10193331
TI - An unusual cutaneous manifestation of myelodysplastic syndrome: "pseudo-Koebner
phenomenon".
AB - An unusual and hitherto unreported complication of myelodysplastic syndrome is
reported: the "pseudo-Koebner phenomenon." The skin lesions were characterised by
exuberant "fleshy" masses at the sites of intravenous cannulation and skin
trauma, and by histological evidence of chronic inflammation with focal necrosis
and abscess formation. No evidence of dermal infiltration by malignant
haemopoietic cells was seen. The exact aetiopathology of the phenomenon is
unclear but an inappropriate and exaggerated inflammatory response owing to
aberrant mediator mechanisms that are known to occur in some cases of
myelodysplastic syndrome may be implicated.
PMID- 10193332
TI - CD5 positive breast carcinoma in a patient with untreated chronic lymphocytic
leukaemia: molecular studies of chromosome 13q.
AB - A 67 year old woman presented with a right breast lump which proved to be a grade
2 invasive ductal carcinoma with axillary lymph node metastasis. She had a five
year history of CD5 positive chronic lymphocytic leukaemia, which never required
treatment. Immunoperoxidase stains for CD5, using the monoclonal antibody NCL-CD
54C7, showed that there was extensive infiltration of axillary lymph nodes with
CD5 positive B lymphocytes. Strong staining for CD5 was also seen in the
carcinoma cells within the breast and lymph node metastases. It has recently been
suggested that there is a tumour suppresser locus in chronic lymphocytic
leukaemia at 13q12.3 near or at the BRCA2 locus. Deletion of regions on
chromosome 13q containing the BRCA2 and RB1 genes has also been reported in
sporadic breast cancers. These observations suggest that there may be a link
between these two diseases acting through chromosome 13, but amplification of
several microsatellite repeat markers failed to show any loss of heterozygosity
or repeat instability at either these or several other loci on chromosome 13.
Examination of additional such cases is needed to perform a more comprehensive
study of the significance of positive CD5 staining of breast carcinoma.
PMID- 10193333
TI - Pancreatic cancer and fibrinogen storage disease.
AB - BACKGROUND: Ductal adenocarcinoma is the most common type of pancreatic carcinoma
while squamous, carcinosarcoma, sarcoma, giant cell carcinoma, and clear cell
types are all rare. Hepatocellular fibrinogen storage disease is also an uncommon
disorder which may be associated with hepatocellular carcinoma. Two cases of
pancreatic carcinoma were encountered in a family with fibrinogen storage
disease, further raising the possibility of a predilection to malignancy in this
unusual disorder. The tumour in one case was of the rare clear cell type. These
two cases are the basis for this report. METHODS: Sections were cut from
retrieved paraffin embedded tissue and stained for routine histology.
Immunohistochemistry using the avidin-biotin technique was applied for the
expression of the markers p53 (D07), carcinoembryonic antigen (CEA), c-erbB-2,
epithelial membrane antigen (EMA), and alpha-fetoprotein (AFP). RESULTS: Both
cases were adenocarcinoma of pancreatic ductal origin. The tumour in one case
showed features of a clear cell carcinoma. The tumour cells expressed p53, CEA,
and EMA immunoreactivity and were negative for c-erbB-2 and AFP. CONCLUSIONS:
Hepatocellular fibrinogen storage disease is rare and has been described in
association with chronic hepatitis, cirrhosis, and rarely with hepatocellular
carcinoma. This represents the first report of its association with carcinoma
outside of the liver.
PMID- 10193334
TI - Malignant fibrothecomatous tumour of the ovary: diagnostic value of anti-inhibin
immunostaining.
AB - Malignant ovarian tumours of the fibrothecoma group are rare. The
clinicopathological features of a case of ovarian malignant fibrothecoma in which
there was metastatic disease in the small intestine and peritoneum at
presentation are described. A number of differential diagnoses were considered
but positive immunohistochemical staining of the resected ovarian and small
intestinal neoplasms with anti-inhibin was of value in confirming a sex cord
stromal tumour and in excluding other lesions. The two tumours were also
ultrastructurally identical. Classical malignant fibrothecomas are said to show
four or more mitotic figures per 10 high power fields (HPF). Although the
intestinal secondary was mitotically active, the primary ovarian tumour contained
only one to two mitoses per 10 HPF, showing that formal mitotic counts are not an
absolute indicator of malignant behaviour in this group of tumours.
PMID- 10193335
TI - Histochemical investigation into the molecular mechanisms of malignant
transformation in a benign glomus tumour.
AB - A glomangiosarcoma arose in a benign glomus tumour. The histological and
immunohistochemical characteristics of the tumour were investigated. Apoptotic
cells were identified by terminal deoxynucleotidyl transferase (TdT) mediated
dUTP-biotin nick end labelling (TUNEL). The proportion of apoptotic cells was
found to be low and TUNEL positive nuclei were present in the benign part of the
tumour. Bcl-2 protein, an inhibitor of apoptosis, was strongly expressed in the
glomangiosarcoma with only weak staining in the benign area. The proliferation
index of the glomangiosarcoma was almost 10-fold higher than that of the benign
glomus tumour. Numerous nuclei in the glomangiosarcoma were intensely stained for
the tumour suppressor protein p53. The results of the this study may contribute
to an understanding of the molecular basis of malignant transformation in benign
glomus tumours.
PMID- 10193336
TI - Borderline malignant change in recurrent mullerian papilloma of the vagina.
AB - Malignant change occurred in a benign, recurrent vaginal mullerian polyp. The
patient, a 49 year old woman with cerebral palsy, presented with a polypoid mass
in the vagina. At four years of age she had presented with a haemorrhagic polyp,
and over the following years she had recurrent irregular bleeding and regrowth of
the polypoidal mass, requiring a total of 10 operations to excise the polyp.
Histological examination of the specimen showed typical mullerian features with
tubal, endometrioid, and endocervical cell types. There were significantly
abnormal nuclei, indicating low grade or borderline malignancy. Review of
previous biopsies showed similar mullerian features but no atypia. This is the
first reported case of borderline malignant change in a previously benign
recurrent mullerian papilloma of the vagina. Definitive radical surgery or
radiotherapy is contraindicated in this patient and she remains under follow up.
PMID- 10193337
TI - Pseudomyxoma ovariilike posttherapeutic alteration in prostate adenocarcinoma.
PMID- 10193338
TI - Inexpensive and reliable haemoglobin colour scale.
PMID- 10193339
TI - Adenocarcinoma of the small bowel, coeliac disease, and lymphocytic gastritis.
PMID- 10193340
TI - In search of a cause of cryptogenic fibrosing alveolitis (CFA): one initiating
factor or many?
AB - The history of patients with idiopathic pulmonary fibrosis (IPF) shows that the
disease may be preceded by a viral-like illness. Although viruses have not been
demonstrated, it is possible that viruses were not detected in culture because
they do not replicate during latency. We investigated the presence of adenovirus
in IPF and interstitial pneumonia associated with collagen vascular disease (CVD
IP), using the nested polymerase chain reaction (PCR) and in situ hybridization
(ISH) for the E1A region of the adenovirus genome. Studies were performed on lung
tissues obtained by transbronchial lung biopsy from 19 patients with IPF, 10
patients with CVD-IP and, for comparison, 20 patients with sarcoidosis. The E1A
DNA was present in 3 out of 19 (16%) cases of IPF, in 5 of 10 (50%) cases of CVD
IP, and in 2 of 20 (10%) cases of sarcoidosis. The incidence of E1A DNA in CVD-IP
was significantly higher than that in sarcoidosis (p < 0.05). In patients with
IPF and CVD-IP, E1A DNA was more prevalent in patients treated with
corticosteroids (6 out of 9 cases; 67%) than in those without it (2 out of 20
cases; 10%) (p < 0.01). ISH studies showed that 1 out of 8 cases of IPF and CVD
IP, in which E1A DNA was detected by PCR, was positive for E1A DNA. We conclude
that adenovirus E1A is unlikely to be aetiologically involved in the pathogenesis
of idiopathic pulmonary fibrosis or interstitial pneumonia associated with
collagen vascular disease. However, a latent adenovirus infection may be
reactivated or may newly infect the host following corticosteroid administration.
PMID- 10193341
TI - Genes, oxidative stress, and the risk of chronic obstructive pulmonary disease.
AB - BACKGROUND: The first-pass metabolism of foreign compounds in the lung is an
important protective mechanism against oxidative stress. We investigated whether
polymorphisms in the gene for microsomal epoxide hydrolase (mEPHX), an enzyme
involved in this protective process, had any bearing on individual susceptibility
to the development of chronic obstructive pulmonary disease (COPD) and emphysema.
METHODS: We designed PCR-based genotyping assays to detect variant forms of mEPHX
that confer slow and fast activity. We used these assays to screen 203 blood
donor controls and groups of patients with asthma (n = 57), lung cancer (n = 50),
COPD (n = 68), and emphysema (n = 94), who were attending specialised clinics in
Edinburgh, UK. FINDINGS: The proportion of individuals with innate slow mEPHX
activity (homozygotes) was significantly higher in both the COPD group and the
emphysema group than in the control group (COPD 13 [19%] vs control 13 [6%];
emphysema 21 [22%] vs 13 [6%]). The odds ratios for homozygous slow activity
versus all other phenotypes were 4.1 (95% CI 1.8-9.7) for COPD and 5.0 (2.3-10.9)
for emphysema. INTERPRETATION: Genetic polymorphisms in xenobiotic enzymes may
have a role in individual susceptibility to oxidant-related lung disease. Epoxide
derivatives of cigarette-smoke components may be the cause of some of the lung
damage characteristics of these diseases.
PMID- 10193343
TI - Diving and the risk of barotrauma.
AB - STUDY OBJECTIVES: Pulmonary barotrauma (PBT) of ascent is a feared complication
in compressed air diving. Although certain respiratory conditions are thought to
increase the risk of suffering PBT and thus should preclude diving, in most cases
of PBT, risk factors are described as not being present. The purpose of our study
was to evaluate factors that possibly cause PBT. DESIGN: We analyzed 15
consecutive cases of PBT with respect to dive factors, clinical and radiologic
features, and lung function. They were compared with 15 cases of decompression
sickness without PBT, which appeared in the same period. RESULTS: Clinical
features of PBT were arterial gas embolism (n = 13), mediastinal emphysema (n =
1), and pneumothorax (n = 1). CT of the chest (performed in 12 cases) revealed
subpleural emphysematous blebs in 5 cases that were not detected in preinjury and
postinjury chest radiographs. A comparison of predive lung function between
groups showed significantly lower midexpiratory flow rates at 50% and 25% of
vital capacity in PBT patients (p < 0.05 and p < 0.02, respectively).
CONCLUSIONS: These results indicate that divers with preexisting small lung cysts
and/or end-expiratory flow limitation may be at risk of PBT.
PMID- 10193342
TI - Update on the "Dutch hypothesis" for chronic respiratory disease.
AB - BACKGROUND: Many patients with chronic obstructive lung disease show increased
airways responsiveness to histamine. We investigated the hypothesis that
increased airways responsiveness predicts the development and remission of
chronic respiratory symptoms. METHODS: We used data from 24-year follow-up (1965
90) of 2684 participants in a cohort study in Vlagtwedde and Vlaardingen,
Netherlands. Increased airways responsiveness was defined as a PC10 value
(concentration of histamine for which challenge led to a 10% fall in forced
expiratory volume in 1 s) of less than 8 mg/ml. Information on respiratory
symptoms was collected by means of a standard questionnaire every 3 years.
Logistic regression was used to control for age, area of residence, cigarette
smoking status, and sex. FINDINGS: Participants with increased airways
responsiveness (1281 observations) were more likely than those without increased
airways responsiveness (5801 observations) to develop the following symptoms
during any 3-year follow-up interval: chronic cough (odds ratio 1.9 [95% CI 1.2
2.9]), chronic phlegm (2.0 [1.3-3.0]), dyspnoea (2.3[1.5-3.5]), asthmatic attacks
(3.7[2.2-6.1]), and persistent wheeze (2.7[1.7-4.4]). The estimate of the odds
ratio for the development of any of the six symptoms was 1.7 (1.2-2.3).
Participants with increased airways responsiveness were less likely than those
without this characteristic to show remission of these respiratory symptoms. The
estimate of the odds ratio for the remission of any of the six symptoms was 0.42
(0.28-0.61). INTERPRETATION: These prospective analyses show that increased
airways responsiveness is positively associated with the development of chronic
respiratory symptoms and negatively associated with the remission of these
symptoms in adults.
PMID- 10193344
TI - Spiral computed tomographic scanning and magnetic resonance angiography for the
diagnosis of pulmonary embolism.
AB - PURPOSE: To compare prospectively the accuracy of spiral computed tomography (CT)
with that of ventilation-perfusion scintigraphy for diagnosing pulmonary
embolism. MATERIALS AND METHODS: Within 48 hours of presentation, 142 patients
suspected of having pulmonary embolism underwent spiral CT, scintigraphy, and
(when indicated) pulmonary angiography. Pulmonary angiography was attempted if
interpretations of spiral CT scans and of scintigrams were discordant or
indeterminate and intermediate-probability, respectively. RESULTS: In the 139
patients who completed the study, interpretations of spiral CT scans and of
scintigrams were concordant in 103 patients (29 with embolism, 74 without). In 20
patients, intermediate-probability scintigrams were interpreted (six with
embolism at angiography, 14 without); diagnosis with spiral CT was correct in 16.
Interpretations of spiral CT scans and those of scintigrams were discordant in 12
cases; diagnosis with spiral CT was correct in 11 cases and that with
scintigraphy was correct in one. Spiral CT and scintigraphic scans of four
patients with embolism did not show embolism. Sensitivities, specificities, and
kappa values with spiral CT and scintigraphy were 87%, 95%, and 0.85 and 65%,
94%, and 0.61, respectively. CONCLUSION: In cases of pulmonary embolism,
sensitivity of spiral CT is greater than that of scintigraphy. Interobserver
agreement is better with spiral CT.
PMID- 10193345
TI - Strategy and cost in investigating solitary pulmonary nodules.
AB - OBJECTIVE: To compare the probability of cancer in a solitary pulmonary nodule
using standard criteria with Bayesian analysis and result of 2-[F-18] fluoro-2
deoxy-D-glucose-positron emission tomographic (FDG-PET) scan. SETTING: A
university hospital and a teaching Veteran Affairs Medical Center. METHODS:
Retrospective analysis of 52 patients who had undergone both CT scan of the chest
and a FDG-PET scan for evaluation of a solitary pulmonary nodule. FDG-PET scan
was classified as abnormal or normal. Utilizing Bayesian analysis, the
probability of cancer using "standard criteria" available in the literature,
based on patient's age, history of previous malignancy, smoking history, size and
edge of nodule, and presence or absence of calcification were calculated and
compared to the probability of cancer based on an abnormal or normal FDG-PET
scan. Histologic study of the nodules was the gold standard. RESULTS: The
likelihood ratios for malignancy in a solitary pulmonary nodule with an abnormal
FDG-PET scan was 7.11 (95% confidence interval [CI], 6.36 to 7.96), suggesting a
high probability for malignancy, and 0.06 (95% CI, 0.05 to 0.07) when the PET
scan was normal, suggesting a high probability for benign nodule. FDG-PET scan as
a single test alone was more accurate than the standard criteria and standard
criteria plus PET scan in correctly classifying nodules as malignant or benign.
CONCLUSION: FDG-PET scan as a single test was a better predictor of malignancy in
solitary pulmonary nodules than the standard criteria using Bayesian analysis.
FDG-PET scan can be a useful adjunct test in the evaluation of solitary pulmonary
nodules.
PMID- 10193346
TI - The cost to society of smoking cessation.
PMID- 10193347
TI - Persistent respiratory effects in survivors of the Bhopal disaster.
AB - OBJECTIVE: To examine the role of exposure to the 1984 Bhopal gas leak in the
development of persistent obstructive airways disease. DESIGN: Cross sectional
survey. SETTING: Bhopal, India. SUBJECTS: Random sample of 454 adults stratified
by distance of residence from the Union Carbide plant. MAIN OUTCOME MEASURES:
Self reported respiratory symptoms; indices of lung function measured by simple
spirometry and adjusted for age, sex, and height according to Indian derived
regression equations. RESULTS: Respiratory symptoms were significantly more
common and lung function (percentage predicted forced expiratory volume in one
second (FEV1), forced vital capacity (FVC), forced expiratory flow between 25%
and 75% of vital capacity (FEF25-75), and FEV1/FEV ratio) was reduced among those
reporting exposure to the gas leak. The frequency of symptoms fell as exposure
decreased (as estimated by distance lived from the plant), and lung function
measurements displayed similar trends. These findings were not wholly accounted
for by confounding by smoking or literacy, a measure of socioeconomic status.
Lung function measurements were consistently lower in those reporting symptoms.
CONCLUSION: Our results suggest that persistent small airways obstruction among
survivors of the 1984 disaster may be attributed to gas exposure.
PMID- 10193348
TI - Role of the indoor environment in determining the severity of asthma.
AB - Allergen exposure can confound the management of asthma. To understand the
potential mechanisms by which allergens increase the steroid requirements in
atopic asthmatics, we examined the effects of allergens on glucocorticoid
receptor (GCR) binding affinity and glucocorticoid (GC) responsiveness of
peripheral blood mononuclear cells (PBMC) from atopic asthmatics. A significant
reduction (p < 0.001) in the GCR binding affinity (Kd) was observed in ragweed
allergic asthmatics during ragweed pollen season compared with PBMC obtained
before and after ragweed season. In vitro effects of allergen on PBMC GCR Kd were
also examined by incubating PBMC from atopic asthmatics with allergen (ragweed
and cat) versus Candida albicans. GCR binding affinity was significantly reduced
after incubation with ragweed (p < 0.001) or cat allergen (p < 0.001) compared
with baseline or C. albicans stimulation. This effect was limited to atopic
asthmatics in that in vitro cat allergen incubation for 48 h failed to
significantly alter GCR binding affinity in nonasthmatic, atopic individuals.
These allergen-induced reductions in GCR binding affinity also rendered the PBMC
less sensitive to the inhibitory effects of hydrocortisone and dexamethasone on
allergen-induced proliferation (p < 0.01). To test the hypothesis that allergen
induced alterations in GCR binding affinity were cytokine-induced, we examined
the effects of interleukin-2 (IL-2) and IL-4 neutralization using anticytokine
antibodies. Addition of both anti-IL-2 and anti-IL-4 antibodies resulted in a
significant (p < 0.001) inhibition of allergen-induced alterations in GCR binding
affinity. Furthermore incubation with cat allergen induced significantly higher
concentrations of IL-2 (p = 0.03) and IL-4 (p = 0.02) by PBMC from atopic as
compared with nonatopic subjects. Our current observations suggest that allergen
exposure may contribute to poor asthma control by reducing GCR binding affinity
in mononuclear cells. This appears to be mediated through IL-2 and IL-4. These
findings may have important implications for novel approaches to the treatment of
poorly controlled asthma.
PMID- 10193349
TI - Effects of anti-IgE in asthmatic subjects.
AB - A humanized murine monoclonal antibody directed to the Fc epsilon R1-binding
domain of human IgE (rhuMAb-E25) has been shown to inhibit the binding of IgE to
mast cells without provoking mast cell activation. To examine the effects of
neutralizing IgE on allergic airway responses, we assessed the effects of 9 wk of
treatment with rhuMAb-E25 in a parallel group, randomized, double-blind, placebo
controlled study of 19 allergic asthmatic subjects. We found that treatment with
rhuMAb-E25 reduced the serum IgE, increased the dose of allergen needed to
provoke an early asthmatic response, reduced the mean maximal fall in FEV1 during
the early response (30 +/- 10% at baseline to 18.8 +/- 8%, versus 33 +/- 8% at
baseline to 34 +/- 4% after placebo; p = 0.01), and reduced the mean maximal fall
in FEV1 during the late response (24 +/- 20% at baseline to 9 +/- 10% versus 20
+/- 17% at baseline to 18 +/- 17% after placebo; p = 0.047). We conclude that an
anti-IgE monoclonal antibody, which inhibits binding of IgE to its receptor,
suppresses the early- and late-phase responses to inhaled allergen in allergic
asthmatic subjects. Targeting IgE with rhuMAb-E25 might be a useful treatment for
allergic asthma.
PMID- 10193350
TI - Oral appliances for the management of snoring and obstructive sleep apnoea.
AB - BACKGROUND: Although oral appliances are effective in some patients with
obstructive sleep apnoea (OSA), they are not universally effective. A novel
anterior mandibular positioner (AMP) has been developed with an adjustable hinge
that allows progressive advancement of the mandible. The objective of this
prospective crossover study was to compare efficacy, side effects, patient
compliance, and preference between AMP and nasal continuous positive airway
pressure (nCPAP) in patients with symptomatic mild to moderate OSA. METHODS:
Twenty four patients of mean (SD) age 44.0 (10.6) years were recruited with a
mean (SD) body mass index of 32.0 (8.2) kg/m2, Epworth sleepiness score 10.7
(3.4), and apnoea/hypopnoea index 26.8 (11.9)/hour. There was a two week wash-in
and a two week wash-out period and two treatment periods (AMP and nCPAP) each of
four months. Efficacy, side effects, compliance, and preference were evaluated by
a questionnaire and home sleep monitoring. RESULTS: One patient dropped out early
in the study and three refused to cross over so treatment results are presented
on the remaining 20 patients. The apnoea/hypopnoea index (AHI) was lower with
nasal CPAP 4.2 (2.2)/hour than with the AMP 13.6 (14.5)/hour (p < 0.01). Eleven
of the 20 patients (55%) who used the AMP were treatment successes (reduction of
AHI to < 10/hour and relief of symptoms), one (5%) was a compliance failure
(unable or unwilling to use the treatment), and eight (40%) were treatment
failures (failure to reduce AHI to < 10/hour and/or failure to relieve symptoms).
Fourteen of the 20 patients (70%) who used nCPAP were treatment successes, six
(30%) were compliance failures, and there were no treatment failures. There was
greater patient satisfaction with the AMP (p < 0.01) than with nCPAP but no
difference in reported side effects or compliance. CONCLUSIONS: AMP is an
effective treatment in some patients with mild to moderate OSA and is associated
with greater patient satisfaction than nCPAP.
PMID- 10193351
TI - Use of fibrinolytic agents in the management of complicated parapneumonic
effusions and empyemas.
AB - BACKGROUND: Standard treatment for pleural infection includes catheter drainage
and antibiotics. Tube drainage often fails if the fluid is loculated by fibrinous
adhesions when surgical drainage is needed. Streptokinase may aid the process of
pleural drainage, but there have been no controlled trials to assess its
efficacy. METHODS: Twenty four patients with infected community acquired
parapneumonic effusions were studied. All had either frankly purulent/culture or
Gram stain positive pleural fluid (13 cases; 54%) or fluid which fulfilled the
biochemical criteria for pleural infection. Fluid was drained with a 14F
catheter. The antibiotics used were cefuroxime and metronidazole or were guided
by culture. Subjects were randomly assigned to receive intrapleural
streptokinase, 250,000 IU daily, or control saline flushes for three days. The
primary end points related to the efficacy of pleural drainage--namely, the
volume of pleural fluid drained and the chest radiographic response to treatment.
Other end points were the number of pleural procedures needed and blood indices
of inflammation. RESULTS: The streptokinase group drained more pleural fluid both
during the days of streptokinase/control treatment (mean (SD) 391 (200) ml versus
124 (44) ml; difference 267 ml, 95% confidence interval (CI) 144 to 390; p <
0.001) and overall (2564 (1663) ml versus 1059 (502) ml; difference 1505 ml, 95%
CI 465 to 2545; p < 0.01). They showed greater improvement on the chest
radiograph at discharge, measured as the fall in the maximum dimension of the
pleural collection (6.0 (2.7) cm versus 3.4 (2.7) cm; difference 2.9 cm, 95% CI
0.3 to 4.4; p < 0.05) and the overall reduction in pleural fluid collection size
(p < 0.05, two tailed Fisher's exact test). Systemic fibrinolysis and bleeding
complications did not occur. Surgery was required by three control patients but
none in the streptokinase group. CONCLUSIONS: Intrapleural streptokinase probably
aids the treatment of pleural infections by improving pleural drainage without
causing systemic fibrinolysis or local haemorrhage.
PMID- 10193352
TI - The study of human sleep: a historical perspective.
PMID- 10193353
TI - Sleep apnoea and snoring: potential links with vascular disease.
PMID- 10193355
TI - Epidemiological insights into the public health burden of sleep disordered
breathing: sex differences in survival among sleep clinic patients.
PMID- 10193354
TI - Sleep apnoea in women.
PMID- 10193356
TI - Sleep apnoea and autonomic function.
PMID- 10193358
TI - Heart block in patients with sleep apnoea.
PMID- 10193357
TI - "Syndrome Z": the interaction of sleep apnoea, vascular risk factors and heart
disease.
PMID- 10193359
TI - Prognosis and sleep disordered breathing in heart failure.
PMID- 10193360
TI - Impact of treatment of sleep apnoea on left ventricular function in congestive
heart failure.
PMID- 10193361
TI - Treatment of central sleep apnoea in congestive heart failure with nasal
ventilation.
PMID- 10193362
TI - CPAP therapy: outcomes and patient use.
PMID- 10193363
TI - Intelligent CPAP systems: clinical experience.
PMID- 10193364
TI - The acute respiratory distress syndrome: fibrosis in the fast lane.
PMID- 10193365
TI - Improving donor lung evaluation: a new approach to increase organ supply for lung
transplantation.
PMID- 10193366
TI - A fresh look at D-dimer in suspected pulmonary embolism.
PMID- 10193367
TI - Fibroproliferation and mast cells in the acute respiratory distress syndrome.
AB - BACKGROUND: Mast cells (MCs), which are a major source of cytokines and growth
factors, have been implicated in various fibrotic disorders. To clarify the
contribution of MCs to fibrogenesis, lung tissue from patients with the acute
respiratory distress syndrome (ARDS) was examined during exudative through to
fibroproliferative stages. METHODS: Lung tissue was obtained from 17 patients
with ARDS who had pathological features of the early exudative stage (n = 6) or
the later reparative stages (n = 11), from four patients with idiopathic
pulmonary fibrosis, and from three patients with normal lung tissue.
Immunohistochemical localisation of tryptase (found in all human MCs), chymase
(found in a subset of human MCs), alpha-smooth muscle actin (identifies
myofibroblasts), and procollagen type I was performed. RESULTS: Normal lung
tissue exhibited myofibroblast and procollagen type I immunolocalisation scores
each of < 5 and MC scores of 1. Increased scores were defined as myofibroblast
and procollagen type I scores of > 10 and MC scores of > or = 2. Eighty percent
of lung tissue samples from the early exudative stage of ARDS exhibited increased
numbers of myofibroblasts, 50% had increased numbers of procollagen type I
producing cells, while only 17% had increased numbers of MCs compared with
control samples. All samples from the later reparative stages of ARDS had
increased numbers of myofibroblasts and procollagen type I producing cells.
Increased numbers of MCs were seen in 55% of samples from the reparative stages.
There was no significant shift in MC phenotype in the ARDS samples. CONCLUSIONS:
Increased numbers of myofibroblasts and procollagen type I producing cells were
frequently found early in the course of ARDS. MC hyperplasia was unusual during
this stage, but was often a feature of the later reparative stages. MCs do not
appear to initiate fibroproliferation in ARDS.
PMID- 10193368
TI - Usefulness of D-dimer, blood gas, and respiratory rate measurements for excluding
pulmonary embolism.
AB - BACKGROUND: A study was undertaken to assess the usefulness of the SimpliRED D
dimer test, arterial oxygen tension, and respiratory rate measurement for
excluding pulmonary embolism (PE) and venous thromboembolism (VTE). METHODS: Lung
scans were performed in 517 consecutive medical inpatients with suspected acute
PE over a one year period. Predetermined end points for objectively diagnosed PE
in order of precedence were (1) a post mortem diagnosis, (2) a positive pulmonary
angiogram, (3) a high probability ventilation perfusion lung scan when the
pretest probability was also high, and (4) the unanimous opinion of an
adjudication committee. Deep vein thrombosis (DVT) was diagnosed by standard
ultrasound and venography. RESULTS: A total of 40 cases of PE and 37 cases of DVT
were objectively diagnosed. The predictive value of a negative SimpliRED test for
excluding objectively diagnosed PE was 0.99 (error rate 2/249), that of PaO2 of >
or = 80 mm Hg (10.7 kPa) was 0.97 (error rate 5/160), and that of a respiratory
rate of < or = 20/min was 0.95 (error rate 14/308). The best combination of
findings for excluding PE was a negative SimpliRED test and PaO2 > or = 80 mm Hg,
which gave a predictive value of 1.0 (error rate 0/93). The predictive value of a
negative SimpliRED test for excluding VTE was 0.98 (error rate 5/249).
CONCLUSIONS: All three of these observations are helpful in excluding PE. When
any two parameters were normal, PE was very unlikely. In patients with a negative
SimpliRED test and PaO2 of > or = 80 mm Hg a lung scan is usually unnecessary.
Application of this approach for triage in the preliminary assessment of
suspected PE could lead to a reduced rate of false positive diagnoses and
considerable resource savings.
PMID- 10193369
TI - Effect of the leukotriene receptor antagonist pranlukast on cellular infiltration
in the bronchial mucosa of patients with asthma.
AB - BACKGROUND: It has been reported that pranlukast reduces the antigen induced
immediate and late phase asthmatic responses, airway hyperreactivity to
acetylcholine, and pulmonary eosinophil accumulation in guinea pigs. A study was
undertaken to test the hypothesis that pranlukast may reduce the number of
inflammatory cells in the bronchial mucosa of patients with asthma. METHODS: A
double blind, placebo controlled study was performed in 17 mild to moderate
asthmatic subjects to examine changes in inflammatory cell infiltration in
response to pranlukast (225 mg orally twice per day for four weeks). Comparisons
of the mean daily beta 2 agonist use, symptom score, FEV1 percentage predicted,
and airway methacholine responsiveness were made before and after treatment.
Using fibreoptic bronchoscopy, bronchial biopsy specimens were obtained before
and after treatment with either pranlukast (n = 10) or placebo (n = 7).
Immunohistology was performed using monoclonal antibodies for CD3, CD4, CD8,
CD68, NP57, AA1, EG1, EG2, gamma GTP and CD19. RESULTS: When the pranlukast and
placebo treated groups were compared there were decreases in beta 2 agonist use,
symptom score, and airway methacholine responsiveness after pranlukast but no
increase in FEV1 was seen. The clinical response in patients treated with
pranlukast was accompanied by a reduction in CD3 (median difference -37, 95%
confidence interval (CI) -69 to -1; p < 0.05), CD4 (median difference -28, 95% CI
-49 to -8; p < 0.01), AA1 (median difference -15, 95% CI -26 to 0; p < 0.05) and
EG2 positive cells (95% CI -35 to 0; p < 0.05), but not in EG1 positive
eosinophils, gamma GTP positive cells, and CD19 positive plasma cells.
CONCLUSIONS: These results support the view that pranlukast may act by inhibition
of bronchial inflammation in patients with asthma.
PMID- 10193370
TI - Air pollution, pollens, and daily admissions for asthma in London 1987-92.
AB - BACKGROUND: A study was undertaken to investigate the relationship between daily
hospital admissions for asthma and air pollution in London in 1987-92 and the
possible confounding and modifying effects of airborne pollen. METHODS: For all
ages together and the age groups 0-14, 15-64 and 65+ years, Poisson regression
was used to estimate the relative risk of daily asthma admissions associated with
changes in ozone, sulphur dioxide, nitrogen dioxide and particles (black smoke),
controlling for time trends, seasonal factors, calendar effects, influenza
epidemics, temperature, humidity, and autocorrelation. Independent effects of
individual pollutants and interactions with aeroallergens were explored using two
pollutant models and models including pollen counts (grass, oak and birch).
RESULTS: In all-year analyses ozone was significantly associated with admissions
in the 15-64 age group (10 ppb eight hour ozone, 3.93% increase), nitrogen
dioxide in the 0-14 and 65+ age groups (10 ppb 24 hour nitrogen dioxide, 1.25%
and 2.96%, respectively), sulphur dioxide in the 0-14 age group (10 micrograms/m3
24 hour sulphur dioxide, 1.64%), and black smoke in the 65% age group (10
micrograms/m3 black smoke, 5.60%). Significant seasonal differences were observed
for ozone in the 0-14 and 15-64 age groups, and in the 0-14 age group there were
negative associations with ozone in the cool season. In general, cumulative lags
of up to three days tended to show stronger and more significant effects than
single day lags. In two-pollutant models these associations were most robust for
ozone and least for nitrogen dioxide. There was no evidence that the associations
with air pollutants were due to confounding by any of the pollens, and little
evidence of an interaction between pollens and pollution except for synergism of
sulphur dioxide and grass pollen in children (p < 0.01). CONCLUSIONS: Ozone,
sulphur dioxide, nitrogen dioxide, and particles were all found to have
significant associations with daily hospital admissions for asthma, but there was
a lack of consistency across the age groups in the specific pollutant. These
associations were not explained by confounding by airborne pollens nor was there
convincing evidence that the effects of air pollutants and airborne pollens
interact in causing hospital admissions for asthma.
PMID- 10193373
TI - Survey of non-invasive ventilation (NIPPV) in patients with acute exacerbations
of chronic obstructive pulmonary disease (COPD) in the UK.
AB - BACKGROUND: Non-invasive positive pressure ventilation (NIPPV) has been shown to
be beneficial in the treatment of acute exacerbations of chronic obstructive
pulmonary disease (COPD) complicated by respiratory failure. A survey was
undertaken to assess the availability of NIPPV for the treatment of acute
exacerbations of COPD and to determine how NIPPV is delivered in hospitals in the
UK. METHODS: A questionnaire was sent to consultants with an interest in
respiratory medicine from 268 of the hospitals found in the BTS directory. The
questionnaire enquired about the hospital as well as the availability of NIPPV in
the hospital. If NIPPV was available in the hospital, details of implementation,
staffing and funding were determined. RESULTS: Replies to the questionnaire were
received from 98.5% of consultants. NIPPV was available in 48% of hospitals,
these hospitals tending to serve larger populations and to have more respiratory
physicians than the hospitals where NIPPV was not available. There was
considerable regional variation in the availability of NIPPV. In hospitals where
NIPPV was not available the reason(s) were lack of consultant training in 53%,
lack of other staff training in 63%, financial in 63%, and doubt about the
benefit of NIPPV in 15% of cases. In those hospitals where NIPPV was available,
clinical practice varied greatly: 68% of centres treated fewer than 20 patients a
year with this form of treatment and 9% treated more than 60 patients a year.
Although NIPPV was paid for completely from the trust equipment budget in 46
hospitals (41%), other money such as research or charitable funds were used at
least partially in the other hospitals and NIPPV was financed solely from
research or charitable funds in 41 hospitals (37%). CONCLUSIONS: Equipment for
NIPPV is available in less than half of the acute hospitals in the UK. In those
in which it is available it is generally underused. Lack of training and problems
with funding are generally given for the failure to introduce NIPPV.
PMID- 10193371
TI - An improved murine model of asthma: selective airway inflammation, epithelial
lesions and increased methacholine responsiveness following chronic exposure to
aerosolised allergen.
AB - BACKGROUND: Existing murine models of asthma lack many of the inflammatory and
epithelial changes that are typical of the human disease. Moreover, these models
are frequently complicated by allergic alveolitis. METHODS: High IgE responder
BALB/c mice were systemically sensitised to ovalbumin and chronically challenged
with low particle mass concentrations of aerosolised ovalbumin. Titres of
antiovalbumin IgE in serum were measured at two weekly intervals by enzyme
immunoassay, accumulation of inflammatory cells and histopathological
abnormalities of the epithelium were quantified morphometrically in the trachea
and the lungs, and airway reactivity was assessed by measuring
bronchoconstriction following intravenous administration of methacholine.
RESULTS: Mice sensitised by two intraperitoneal injections of ovalbumin developed
high titres of IgE antibodies to ovalbumin. Following exposure to low
concentrations of aerosolised antigen for up to eight weeks these animals
developed a progressive inflammatory response in the airways, characterised by
the presence of intraepithelial eosinophils and by infiltration of the lamina
propria with lymphoid/mononuclear cells, without associated alveolitis. Goblet
cell hyperplasia/metaplasia was induced in the intrapulmonary airways, while
epithelial thickening and subepithelial fibrosis were evident following chronic
exposure. In parallel, the mice developed increased sensitivity to induction of
bronchospasm, as well as increased maximal reactivity. Non-immunised mice exposed
to aerosolised ovalbumin had low or absent antiovalbumin IgE and did not exhibit
inflammatory or epithelial changes, but developed airway hyperreactivity.
CONCLUSIONS: This experimental model replicates many of the features of human
asthma and should facilitate studies of pathogenetic mechanisms and of potential
therapeutic agents.
PMID- 10193372
TI - Pulmonary artery pressure variation in patients with connective tissue disease:
24 hour ambulatory pulmonary artery pressure monitoring.
AB - BACKGROUND: The specific contribution of secondary pulmonary hypertension to the
morbidity and mortality of patients with underlying lung disease can be difficult
to assess from single measurements of pulmonary artery pressure. We have studied
patients with secondary pulmonary hypertension using an ambulatory system for
measuring continuous pulmonary artery pressure (PAP). We chose to study patients
with connective tissue disease because they represent a group at high risk of
pulmonary vascular disease, but with little disturbance of lung function.
METHODS: Six patients (five with progressive systemic sclerosis and one with
systemic lupus erythematosis) were studied. They underwent preliminary
cardiopulmonary investigations followed by Doppler echocardiography, right heart
catheterisation, and ambulatory pulmonary artery pressure monitoring to measure
changes in pressure over a 24 hour period including during a formal exercise
test. RESULTS: All patients had pulmonary hypertension as measured by Doppler
echocardiography with estimated pulmonary artery systolic pressures of 40-100 mm
Hg. Pulmonary function testing revealed virtually normal spirometric values (mean
FEV1 86.9% predicted) but marked reduction in CO gas transfer factor (KCO 57.8%
predicted). Exercise responses were impaired with mean VO2max 50.6% predicted.
Ambulatory PAP monitoring indicated significant changes in pressures with
variation in posture and activity throughout 24 hours. Resting PAP did not
predict the change in PAP seen on exercise. CONCLUSION: Conventional methods of
assessment of the pulmonary circulation based on single measurements in the
supine position may underestimate the stresses faced by the right side of the
circulation. This ambulatory system allows monitoring of pulmonary haemodynamics
continuously over 24 hours during normal activities of daily living. These
measurements may increase our understanding of the contribution made by secondary
pulmonary hypertension to the morbidity and mortality of the underlying lung
disease.
PMID- 10193374
TI - Increased levels of exhaled carbon monoxide in bronchiectasis: a new marker of
oxidative stress.
AB - BACKGROUND: Bronchiectasis is a chronic inflammatory lung disease associated with
increased production of oxidants due mostly to neutrophilic inflammation.
Induction of heme oxygenase (HO-1) by reactive oxygen species is a general
cytoprotective mechanism against oxidative stress. HO-1 catabolises heme to
bilirubin, free iron and carbon monoxide (CO). Exhaled CO measurements may
therefore reflect an oxidative stress and be clinically useful in the detection
and management of inflammatory lung disorders. METHODS: The levels of exhaled CO
of 42 non-smoking patients with bronchiectasis treated or not treated with
inhaled corticosteroids were compared with CO levels in 37 normal non-smoking
subjects. RESULTS: Levels of exhaled CO were raised in patients with
bronchiectasis, both those treated with inhaled corticosteroids (n = 27, median
5.5 ppm, 95% CI 5.16 to 7.76) and those not treated with inhaled corticosteroids
(n = 15, median 6.0 ppm. 95% CI 4.74 to 11.8), compared with normal subjects (n =
37, median 3.0 ppm, 95% CI 2.79 to 3.81, p = 0.0024). There was no correlation
between exhaled CO and HbCO levels (r = 0.42, p = 0.12) in normal subjects (n =
7), nor between the urine cotinine concentration and exhaled CO levels (r = 0.2,
p = 0.12). CONCLUSIONS: Increased levels of exhaled CO may reflect induction of
HO-1 and oxidative stress in bronchiectasis. Measurement of exhaled CO may be
useful in the management of bronchiectasis and possibly other chronic
inflammatory lung disorders.
PMID- 10193376
TI - Updating UK estimates of age, sex and period specific cumulative constant tar
cigarette consumption per adult.
AB - BACKGROUND: In 1993 we presented age and sex specific estimates of cumulative
constant tar cigarette consumption (CCTCC) per adult for five year periods to
1986-90. These were derived from annual surveys conducted for the Tobacco
Manufacturers' Association (TMA) since 1946, extrapolated back to 1891 for men
and to 1921 for women and corrected for the decline in average (machine smoked)
tar levels. We now provide estimates for 1991-5. METHODS: TMA surveys having
ceased, 1991-5 estimates of manufactured cigarette consumption per adult (MCA)
were derived from the General Household Survey (GHS) and corrected for the
continuing decline in tar. These estimates were divided by 0.75 (men) and 0.80
(women), based on a comparison of GHS and TMA data for 1971-90, to allow
accumulation with the TMA derived estimates prior to 1991. RESULTS: For both
sexes the GHS/TMA ratio of MCA varied little by age or five year period,
justifying the use of the correction factors when adjusting GHS estimates for
1991-95. TMA estimates were higher than GHS estimates as only TMA sales-corrected
their data for understatement of smoking and the surveys differed in questions on
handrolled cigarette smoking. The 1991-95 data confirm the continuing decline in
CCTCC at all ages in men. Women show a less steep decline for ages 30-64 and an
increase for ages 65-84. CONCLUSION: The GHS data can validly be used to update
the CCTCC estimates. Some reservations about the use of CCTCC are discussed.
PMID- 10193375
TI - Mycobacterium tuberculosis DNA in tissues affected by sarcoidosis.
AB - BACKGROUND: Although some studies have reported the presence of Mycobacterium
tuberculosis (MTb) DNA in tissues affected by sarcoidosis, the data are
conflicting. The aim of this study was to collect prospectively tissue from
patients with sarcoidosis in whom tuberculosis had been excluded, and to use
polymerase chain reaction (PCR) to search for DNA sequences specific for MTb.
METHODS: Fresh tissue samples (node or lung biopsy) taken from 23 patients with
newly diagnosed sarcoidosis, 10 with other respiratory disease, and four patients
with culture positive tuberculosis were analysed using PCR to amplify a 123 bp
fragment of IS6110, the insertion element present in MTb, and nested PCR to
further amplify an 85 bp sequence within the 123 bp product. DNA was also
extracted from formalin fixed tissue from eight additional patients with
sarcoidosis. RESULTS: MTb DNA was not detected in any of the tissue samples from
patients with sarcoidosis or other respiratory disease but was found in all four
patients with tuberculosis. CONCLUSIONS: This study has shown the absence of MTb
DNA in lymph node and lung biopsy samples from patients with sarcoidosis. MTb is
therefore unlikely to be a factor in the pathogenesis of this disease.
PMID- 10193377
TI - Silver/silver chloride electrodes for measurement of potential difference in
human bronchi.
AB - BACKGROUND: An easy and reliable method to measure potential difference (PD) in
the lower airways would be of interest in the field of cystic fibrosis. We have
developed silver/silver chloride (Ag/AgCl) electrodes to measure PD in the lower
airways. METHODS: To validate this technique the nasal PD measured with Ag/AgCl
electrodes and with conventional perfused electrodes was compared in 16 patients.
The range of PD measured with Ag/AgCl electrodes in the lower airways during
fibreoptic bronchoscopy was determined in 14 adult patients and in nine the
reproducibility of this technique was examined. RESULTS: Nasal PD values measured
with Ag/AgCl and perfused electrodes were highly correlated (r = 0.985, p <
0.0001) and the limits of agreement (mean +/- 2SD of the difference) between the
two methods were -1.91 mV and 1.53 mV. In the lower airways a progressive and
slight decrease in PD values with decreasing airway diameter was observed in most
patients. The mean (2SD) of the differences between the two tracheal measurements
was 0.21 (1.73) mV. CONCLUSIONS: The use of Ag/AgCl electrodes gives a reliable
and reproducible measurement of PD in the lower airways in humans.
PMID- 10193378
TI - Endogenous nitric oxide in patients with stable COPD: correlates with severity of
disease.
AB - BACKGROUND: Increased levels of exhaled nitric oxide (eNO) have been reported in
asthmatic subjects but little information is available on eNO in patients with
advanced chronic obstructive pulmonary disease (COPD). A study was undertaken to
evaluate the levels of eNO in patients with stable COPD of different degrees of
severity. METHODS: Peak and plateau values of eNO (PNO and PLNO, respectively)
were evaluated in 53 patients with COPD and analysed according to the level of
forced expiratory volume in one second (FEV1) and the presence of cor pulmonale
(CP) (group 1, FEV1 < 35% predicted with CP, n = 15; group 2, FEV1 < 35%
predicted without CP, n = 15; group 3, FEV1 > 35% predicted, n = 23). Seventeen
normal subjects served as controls. RESULTS: All the patients with COPD had
reduced levels of PLNO compared with the controls (mean (SD) 6.3 (3.0) and 9.4
(2.8) ppb, respectively). In groups 1 and 2 PLNO levels were significantly lower
than in subjects in group 3 (5.5 (2.9), 5.7 (3.5), and 7.1 (2.7) ppb,
respectively; p < 0.01 ANOVA). In all subjects % predicted FEV1 correlated
slightly with PLNO but not with PNO. CONCLUSION: Patients with severe stable COPD
have reduced levels of eNO compared with normal subjects. eNO levels are slightly
related to the severity of airflow obstruction.
PMID- 10193379
TI - Health effects of passive smoking. 9. Parental smoking and spirometric indices in
children.
AB - BACKGROUND: A systematic quantitative review was conducted of the evidence
relating parental smoking to spirometric indices in children. METHODS: An
electronic search of the Embase and Medline databases was completed in April 1997
and identified 692 articles from which we included four studies in neonates, 42
cross-sectional studies in school aged children (22 were included in a meta
analysis), and six longitudinal studies of lung function development. RESULTS: In
a pooled analyses of 21 surveys of school aged children the percentage reduction
in forced expiratory volume in one second (FEV1) in children exposed to parental
smoking compared with those not exposed was 1.4% (95% CI 1.0 to 1.9). Effects
were greater on mid expiratory flow rates (5.0% reduction, 95% CI 3.3 to 6.6) and
end expiratory flow rates (4.3% reduction, 95% CI 3.1 to 5.5). Adjustment for
potential confounding variables had little effect on the estimates. A number of
studies reported clear evidence of exposure response. Where exposure was
explicitly identified it was usually maternal smoking. Two studies in neonates
have reported effects of prenatal exposure to maternal smoking. Of five cross
sectional studies that compared effects of perinatal exposure (retrospectively
assessed) with current exposure to maternal smoking in later childhood, the three
largest concluded that the major effect was in utero or neonatal exposure.
Longitudinal studies suggest a small effect of current exposure on growth in lung
function, but with some heterogeneity between studies. CONCLUSIONS: Maternal
smoking is associated with small but statistically significant deficits in FEV1
and other spirometric indices in school aged children. This is almost certainly a
causal relationship. Much of the effect may be due to maternal smoking during
pregnancy.
PMID- 10193380
TI - Genetics and pulmonary medicine. 6. Immotile cilia syndrome: past, present, and
prospects for the future.
PMID- 10193382
TI - Disseminated Penicillium marneffei infection presenting as a right upper lobe
mass in an HIV positive patient.
AB - A 35 year old HIV positive patient from Hong Kong presented with a fever, cough
and a skin rash in association with a lung mass, all of which were due to
disseminated Penicillium marneffei infection. He made a good response to
antifungal therapy. The lung mass is a previously undescribed pulmonary
manifestation of disseminated Penicillium marneffei infection. Infections with
this fungus should be suspected in any patient with HIV and respiratory symptoms
who has visited southeast Asia.
PMID- 10193381
TI - Respiratory illness: a complementary perspective.
PMID- 10193383
TI - Flitting radiographic shadows: an unusual presentation of cancer in the lungs.
AB - Tumour involvement of pulmonary blood vessels occurs frequently in advanced lung
cancer and occasionally may cause pulmonary infarction. A case is reported of
diffuse obstruction of pulmonary arteries by cancer in which no primary tumour
was found, and which presented as flitting radiographic opacities due to
pulmonary infarction.
PMID- 10193384
TI - Asthma in African cities.
PMID- 10193385
TI - Infections in asthma and allergy.
PMID- 10193386
TI - Viruses and asthma exacerbations.
PMID- 10193387
TI - Telomerase activity in human pleural mesothelioma.
AB - BACKGROUND: Gradual telomere erosion eventually limits the replicative life span
of somatic cells and is regarded as an ultimate tumour suppressor mechanism,
eliminating cells that have accumulated genetic alterations. Telomerase, which
has been found in over 85% of human cancers, elongates telomeres and may be
required for tumorigenesis by the process of immortalisation. Malignant
mesothelioma is an incurable malignancy with a poor prognosis. The disease
becomes symptomatic decades after exposure to carcinogenic asbestos fibres,
suggesting the long term survival of pre-malignant cell clones. This study
investigated the presence of telomerase in pleural malignant mesothelioma, which
may be the target for future anti-telomerase drugs. METHODS: Telomerase activity
was semiquantitatively measured in extracts from 22 primary pleural
mesotheliomas, two benign solitary fibrous tumours of the pleura, four
mesothelioma cell lines, and six short term mesothelial cell cultures from normal
pleura using a non-isotopic dilution assay of the telomeric repeat amplification
protocol. RESULTS: Twenty of the 22 primary mesotheliomas (91%) and all tumour
derived mesothelioma cell lines were telomerase positive. Different levels of
enzyme activity were observed in the tumours of different histological subtypes.
Telomerase activity could not be detected in the six normal mesothelial cell
cultures or in the two mesotheliomas. Both benign solitary fibrous tumours showed
strong telomerase activity. CONCLUSIONS: Telomerase activity is found in a high
proportion of mesotheliomas and anti-telomerase drugs might therefore be useful
clinically. The results are consistent with the hypothesis that telomerase
activity may be a feature of carcinogenesis in mesotheliomas and possibly in many
other cancers.
PMID- 10193388
TI - Prevalence of exercise induced bronchospasm in Kenyan school children: an urban
rural comparison.
AB - BACKGROUND: Higher rates of exercise induced bronchospasm (EIB) have been
reported for urban than for rural African schoolchildren. The change from a
traditional to a westernized lifestyle has been implicated. This study was
undertaken to examine the impact of various features of urban living on the
prevalence of EIB in Kenyan school children. METHODS: A total of 1226 children
aged 8-17 years attending grade 4 at five randomly selected schools in Nairobi
(urban) and five in Muranga district (rural) underwent an exercise challenge
test. A respiratory health and home environment questionnaire was also
administered to parents/guardians. This report is limited to 1071 children aged <
or = 12 years. Prevalence rates of EIB for the two areas were compared and the
differences analysed to model the respective contributions of personal
characteristics, host and environmental factors implicated in childhood asthma.
RESULTS: A fall in forced expiratory volume in one second (FEV1) after exercise
of > or = 10% occurred in 22.9% of urban children and 13.2% of rural children (OR
1.96, 95% CI 1.41 to 2.71). The OR decreased to 1.65 (95% CI 1.10 to 2.47) after
accounting for age, sex, and host factors (a family history of asthma and breast
feeding for less than six months), and to 1.21 (95% CI 0.69 to 2.11) after
further adjustment for environmental factors (parental education, use of biomass
fuel and kerosene for cooking, and exposure to motor vehicle fumes). CONCLUSIONS:
The EIB rates in this study are higher than any other reported for African
children, even using more rigorous criteria for EIB. The study findings support a
view which is gaining increasing credence that the increase in prevalence of
childhood asthma associated with urbanisation is the consequence of various
harmful environmental exposures acting on increasingly susceptible populations.
PMID- 10193389
TI - Early childhood infection and atopic disorder.
AB - BACKGROUND: Atopy is of complex origins but the recent rise in atopic diseases in
westernized communities points to the action of important environmental effects.
One candidate mechanism is the changing pattern of microbial exposure in
childhood. This epidemiological study investigated the relationship between
childhood infections and subsequent atopic disease, taking into account a range
of social and medical variables. METHODS: A total of 1934 subjects representing a
retrospective 1975-84 birth group at a family doctor practice in Oxfordshire were
studied. Public health and practice records were reviewed; temporal records were
made of all diagnoses of infections and their treatments, all immunisations, and
diagnoses of asthma, hay fever and eczema; maternal atopy and a number of other
variables were documented. RESULTS: Logistic regression analysis identified three
statistically significant predictors of subsequent atopic disease: maternal atopy
(1.97, 95% CI 1.46 to 2.66, p < 0.0001), immunisation with whole-cell pertussis
vaccine (1.76, 95% CI 1.39 to 2.23, p < 0.0001), and treatment with oral
antibiotics in the first two years of life (2.07, 95% CI 1.64 to 2.60, p <
0.0001). There was no significant association found for maternal smoking, bottle
feeding, sibship size, or social class. CONCLUSIONS: The prediction of atopic
disease by maternal atopy mainly reflects the effect of acknowledged genetic
factors. Interpretation of the prediction of atopic disorders by immunisation
with wholecell pertussis vaccine and treatment with oral antibiotics needs to be
very cautious because of the possibilities of confounding effects and reverse
causation. However, plausible immune mechanisms are identifiable for the
promotion of atopic disorders by both factors and further investigation of these
association is warranted.
PMID- 10193390
TI - Repeatability of lung function tests during methacholine challenge in wheezy
infants.
AB - BACKGROUND: The repeatability of lung function tests and methacholine inhalation
tests was evaluated in recurrently wheezy infants over a one month period using
the rapid thoracic compression technique. METHODS: Eighty-one wheezy, symptom
free infants had pairs of methacholine challenge tests performed one month apart.
Maximal flow at functional residual capacity (VmaxFRC) and transcutaneous oxygen
tension (Ptco2) were measured at baseline and after methacholine inhalation.
Provocative doses of methacholine causing a 15% fall in Ptco2 (PD15 Ptco2) or a
30% fall in VmaxFRC (PD30 VmaxFRC) were determined. RESULTS: Large changes in
VmaxFRC were measured from T1 to T2 with a mean difference between measurements
(T2-T1) of 7 (113) ml/s and a 95% range for a single determination for VmaxFRC of
160 ml/s. The mean (SD) difference between pairs of PD30 VmaxFRC measurements was
0.33 (1.89) doubling doses with a 95% range for a single determination of 2.7
doubling doses. Repeatability of PD15Ptco2 was similar. A change of 3.7 doubling
doses of methacholine measured on successive occasions represents a significant
change. CONCLUSIONS: Baseline VmaxFRC values are highly variable in wheezy,
symptom free infants. Using either VmaxFRC or Ptco2 as the outcome measure for
methacholine challenges provided similar repeatability. A change of more than 3.7
doubling doses of methacholine is required for clinical significance.
PMID- 10193391
TI - Environmental correlates of impaired lung function in non-smokers with severe
alpha 1-antitrypsin deficiency (PiZZ).
AB - BACKGROUND: Active smoking is the most important risk factor for pulmonary
emphysema in subjects with severe alpha 1-antitrypsin (AAT) deficiency. The aim
of this study was to analyse the effects of environmental risk factors other than
active smoking on lung function and on respiratory symptoms in non-smoking PiZZ
individuals. METHODS: Lifetime exposure to passive smoking, domiciliary use of a
kerosene (paraffin) heater or gas cooker, and all occupations since leaving
school were reported by 205 non-smoking PiZZ individuals (95 men and 110 women)
included in the Swedish AAT deficiency register. Lung function test results and
histories of respiratory symptoms (chronic bronchitis, recurrent wheezing, and
exertional dyspnoea) were elicited from the AAT register records. RESULTS: After
adjustment for age, agricultural employment and domiciliary kerosene heater
usage, but not gas cooker usage or passive smoking, were both associated with
significantly decreased lung function. Multiple linear regression analysis showed
age, sex, kerosene heater usage, and agricultural employment to be independent
determinants of lung function impairment. Age and passive smoking for 10 years or
more, both at home and at the work place, were associated with the presence of
chronic bronchitis. Age and agricultural employment for > or = 10 years were
associated with recurrent wheezing and exertional dyspnoea. CONCLUSIONS:
Domiciliary kerosene heater usage and an agricultural occupation therefore appear
to be environmental factors associated with decreased lung function in non
smoking PiZZ individuals, and passive smoking is associated with an increased
frequency of chronic bronchitis, but not with impaired lung function.
PMID- 10193392
TI - Effect of breathing circuit resistance on the measurement of ventilatory
function.
AB - BACKGROUND: The American Thoracic Society (ATS) has set the acceptable resistance
for spirometers at less than 1.5 cm H2O/l/s over the flow range 0-14 l/s and for
monitoring devices at less than 2.5 cm H2O/l/s (0-14 l/s). The aims of this study
were to determine the resistance characteristics of commonly used spirometers and
monitoring devices and the effect of resistance on ventilatory function. METHODS:
The resistance of five spirometers (Vitalograph wedge bellows, Morgan rolling
seal, Stead Wells water sealed, Fleisch pneumotachograph, Lilly pneumotachograph)
and three monitoring devices (Spiro 1, Ferraris, mini-Wright) was measured from
the back pressure developed over a range of known flows (1.6-13.1 l/s). Peak
expiratory flow (PEF), forced expiratory flow in one second (FEV1), forced vital
capacity (FVC), and mid forced expiratory flow (FEF25-75%) were measured on six
subjects with normal lung function and 13 subjects with respiratory disorders
using a pneumotachograph. Ventilatory function was then repeated with four
different sized resistors (approximately 1-11 cmH2O/l/s) inserted between the
mouthpiece and pneumotachograph. RESULTS: All five diagnostic spirometers and two
of the three monitoring devices passed the ATS upper limit for resistance. PEF,
FEV1 and FVC showed significant (p < 0.05) inverse correlations with added
resistance with no significant difference between the normal and patient groups.
At a resistance of 1.5 cm H2O/l/s the mean percentage falls (95% confidence
interval) were: PEF 6.9% (5.4 to 8.3); FEV1 1.9% (1.0 to 2.8), and FVC 1.5% (0.8
to 2.3). CONCLUSIONS: The ATS resistance specification for diagnostic spirometers
appears to be appropriate. However, the specification for monitoring devices may
be too conservative. PEF was found to be the most sensitive index to added
resistance.
PMID- 10193393
TI - Impact of nasal ventilation on survival in hypercapnic Duchenne muscular
dystrophy.
AB - BACKGROUND: Respiratory failure is the commonest cause of death in patients with
Duchenne muscular dystrophy (DMD). Life expectancy is less than one year once
diurnal hypercapnia develops. This study examines the effects of nasal
intermittent positive pressure ventilation (NIPPV) on survival in symptomatic
Duchenne patients with established ventilatory failure. METHODS: Nocturnal NIPPV
was applied in 23 consecutive patients with DMD of mean (SD) age 20.3 (3.4) years
who presented with diurnal and nocturnal hypercapnia. RESULTS: One year and five
year survival rates were 85% (95% CI 69 to 100) and 73% (95% CI 53 to 94),
respectively. Early changes in arterial blood gas tensions following NIPPV
occurred with mean (SD) PO2 increasing from 7.6 (2.1) kPa to 10.8 (1.3) kPa and
mean (SD) PCO2 falling from 10.3 (4.5) kPa to 6.1 (1.0) kPa. Improvements in
arterial blood gas tensions were maintained over five years. Health perception
and social aspects of SF-36 health related quality of life index were reported as
equivalent to other groups with nonprogressive disorders using NIPPV.
CONCLUSIONS: Nasal ventilation is likely to increase survival in hypercapnic
patients with Duchenne muscular dystrophy and should be considered as a treatment
option when ventilatory failure develops.
PMID- 10193394
TI - Comparison of spontaneous and induced sputum for investigation of airway
inflammation in chronic obstructive pulmonary disease.
AB - BACKGROUND: Although sputum induction is used as a technique to investigate lower
airway inflammation in asthmatic subjects, advantages over spontaneous sputum in
patients with chronic obstructive pulmonary disease (COPD) have not been
investigated. METHODS: Samples of spontaneous sputum and sputum induced with 3%
hypertonic saline for 14 minutes were collected from 27 patients with chronic
obstructive pulmonary disease (COPD) who usually produced spontaneous sputum.
Spirometric indices and oxygen saturation (Sao2) were measured at seven minute
intervals. The spontaneous, seven and 14 minute sputum samples were analysed for
total and differential cell counts, cell viability, and interleukin 8 levels.
RESULTS: Analysis of the sputum revealed that median cell viability was higher in
the seven minute (62.8%; p = 0.004) and 14 minute (65%; p = 0.001) induced sputum
samples than in spontaneous sputum (41.2%). There was no significant difference
in total and differential cell counts or in interleukin 8 levels between
spontaneous and induced sputum. During the sputum induction procedure the mean
(SD) fall in forced expiratory volume in one second (FEV1) was 0.098 (0.111) 1 (p
< 0.001) and in forced vital capacity (FVC) was 0.247 (0.233) 1 (p < 0.001).
There was a small but significant fall in Sao2 during sputum induction (p =
0.03). CONCLUSIONS: Induced sputum contains a higher proportion of viable cells
than spontaneous sputum. There are no significant differences between the sputum
samples obtained at seven minutes and at 14 minutes of hypertonic saline
nebulisation. Sputum induction is safe and well tolerated in patients with COPD.
PMID- 10193395
TI - Efficacy of nasal continuous positive airway pressure therapy in chronic heart
failure: importance of underlying cardiac rhythm.
AB - BACKGROUND: Some previous reports have indicated beneficial cardiac effects of
nasal continuous positive airway pressure (NCPAP) in patients with severe
congestive heart failure (CHF), but others have reported deleterious cardiac
effects, particularly among patients in atrial fibrillation (AF). The aim of this
study was to determine if differences in cardiac rhythm influence the acute
cardiac response to NCPAP. METHODS: Eleven consecutive patients with CHF were
recruited, six in atrial fibrillation (AF) and five with sinus rhythm (SR).
Cardiac index was measured during awake NCPAP application by the thermodilution
technique during cardiac catheterisation. NCPAP was applied in a randomised
sequence at pressures of 0, 5, and 10 cm H2O with three 30 minute applications
separated by 20 minute recovery periods without NCPAP. RESULTS: Significant
differences were found between the AF and SR groups for cardiac index responses
to NCPAP (p = 0.004, ANOVA) with a fall in cardiac index in the AF group (p =
0.02) and a trend towards an increase in the SR group (p = 0.10). Similar
differences were seen between the groups in stroke volume index responses but not
in heart rate responses. Changes in systemic vascular resistance were also
significantly different between the two groups (p < 0.005, ANOVA), rising in the
AF group but falling in the SR group. CONCLUSIONS: These data indicate an
important effect of underlying cardiac rhythm on the awake haemodynamic effects
of NCPAP in patients with CHF.
PMID- 10193396
TI - Gastro-oesophageal reflux related cough and its response to laparoscopic
fundoplication.
AB - BACKGROUND: This study was designed to determine prospectively the rate of cough
before and after laparoscopic Nissen fundoplication performed for the control of
gastro-oesophageal reflux disease. METHODS: One hundred and ninety five
consecutive patients (76 men) of mean (SD) age 46.9 (14.1) years with proven
gastro-oesophageal reflux disease, who were either on long term omeprazole (n =
187) or who had not responded to a trial of omeprazole (n = 8), took part in the
study which was carried out in a university teaching hospital that included a
regional respiratory referral centre. Patients underwent oesophageal manometry,
24 hour oesophageal pH testing, and symptom score evaluation by an independent
observer before and six months after laparoscopic Nissen fundoplication. RESULTS:
One hundred and thirty three patients presented with reflux symptoms and 62 with
respiratory symptoms; 68% of patients complained of cough before surgery (86%
with respiratory symptoms, 60% with gastrointestinal symptoms). The percentage
reflux time in 24 hours fell significantly (p < 0.0001) from a mean (SD) of 9.38
(10.99)% to 1.22 (2.92)%, lower oesophageal sphincter tone rose significantly (p
< 0.0001) from a mean (SD) of 7.71 (5.90) mm Hg to 21.74 (10.84) mm Hg, and the
cough score fell from a median value of 8.0 (IQR 12.0) to 0 (IQR 3) following
surgery. Of the patients with cough, 51% were cough free after surgery and 31%
improved. The patients with respiratory symptoms had a higher cough score before
(median 12.0 (IQR 5.5) versus 4.0 (IQR 8.75), p < 0.0001) and after surgery
(median 1 (7.5) versus 0.0 (IQR 1.0), p = 0.0045) than those with
gastrointestinal symptoms. CONCLUSIONS: Patients who present to
gastroenterologists with severe reflux commonly complain of cough. Laparoscopic
Nissen fundoplication is effective in the control of cough in patients with
gastro-oesophageal reflux disease, with or without primary respiratory disease.
PMID- 10193397
TI - Detection of anti-cytokeratin 8 antibody in the serum of patients with
cryptogenic fibrosing alveolitis and pulmonary fibrosis associated with collagen
vascular disorders.
AB - BACKGROUND: It has been suggested that the humoral immune system plays a role in
the pathogenesis of cryptogenic fibrosing alveolitis (CFA). Although circulating
autoantibodies to lung protein(s) have been suggested, none of the lung proteins
have been characterised. The purpose of this study was to determine the antigen
to which the serum from patients with pulmonary fibrosis reacted. METHODS: The
anti-A549 cell antibody was characterised in a patient with CFA using Western
immunoblotting and immunohistochemical staining of A549 cells. As we identified
that one of the antibodies against A549 cells was anti-cytokeratin 8, the
expression of mRNA of cytokeratin 8 in A549 cells was evaluated. In addition, we
attempted to establish an enzyme linked immunosorbent assay to measure the levels
of anti-cytokeratin 8 antibody in the serum of patients with CFA and pulmonary
fibrosis associated with collagen vascular disorders (PF-CVD). RESULTS: Initially
two anti-A549 cell antibodies were detected in the serum of patients with
pulmonary fibrosis, one of which was characterised as anticytokeratin 8 antibody
by Western immunoblotting. We were able to establish an ELISA to measure anti
cytokeratin 8 antibody and found significantly higher levels in patients with CFA
and PF-CVD than in normal volunteers, patients with sarcoidosis, pneumonia, and
pulmonary emphysema. CONCLUSIONS: One of the anti-A549 cell antibodies in the
serum of patients with CFA was against cytokeratin 8. The serum levels of anti
cytokeratin 8 antibody were increased in patients with CFA and PF-CVD. These
results suggest that anticytokeratin 8 antibody may be involved in the process of
lung injury in pulmonary fibrosis.
PMID- 10193398
TI - Effects of Aspergillus fumigatus culture filtrate on antifungal activity of human
phagocytes in vitro.
AB - BACKGROUND: Aspergillus fumigatus can colonise the airways and the lungs with
localised underlying conditions and occasionally invade the surrounding lung
tissues even in subjects without systemic predisposing factors, presumably by
escaping the local host defences. The aim of this study was to investigate the
effects of A fumigatus culture filtrate (ACF) on the activities of human
phagocytes--inhibition of germination of A fumigatus spores by alveolar
macrophages (AMs) and hyphal damage by polymorphonuclear leucocytes (PMNs)--which
are the critical host defences against A fumigatus. METHODS: Spores were
incubated with AMs at a ratio of 1:1 in a medium containing different
concentrations of ACF for 10 hours at 37 degrees C. Spore germination was
visualised with light microscopy and the inhibition rate was calculated. The
percentage of hyphal damage caused by PMNs pretreated with various concentrations
of ACF was measured by a colorimetric tetrazolium metabolic assay. RESULTS: The
inhibition rate of spore germination by AMs cultured with medium alone (control)
was 90 (0.8)% whereas that by AMs cultured with the medium containing 10% ACF was
significantly (p < 0.05) reduced to 41.7 (4.6)%. ACF suppressed the inhibition of
spore germination in a dose dependent manner without altering the phagocytosing
activity against the spores. The percentage of hyphal damage caused by PMNs
pretreated with medium-199 (control) was 78.1 (2.3)% compared with 65.3 (2.8)%
when PMNs were pretreated with 50% ACF (p < 0.05). CONCLUSIONS: A fumigatus
releases biologically active substance(s) which suppress the inhibition of spore
germination by AMs and also suppress PMN mediated hyphal damage, and thus may
contribute to the pathogenicity of this fungus.
PMID- 10193399
TI - Genetics and pulmonary medicine. 7. Somatic mutations in the development of lung
cancer.
AB - Lung cancers exhibit complex heterogeneous karyotypes and to date sequencing the
serial somatic mutations which give rise to malignant change has proved
difficult. Cigarette smoke causes a field change in the respiratory mucosa with
mutations demonstrable even in histologically normal areas. After smoking
cessation many of these mutations seem to persist indefinitely so that the risk
of an ex-smoker developing lung cancer never reverts to that of a life-long non
smoker. Demonstration of specific somatic mutations in biopsy or sputum samples
may eventually provide a useful method of screening for lung cancer. Somatic
mutations give useful information about prognosis in non-small cell lung cancer
and they are the key to exciting future retroviral and monoclonal antibody
mediated therapies.
PMID- 10193400
TI - Methodology of bronchial responsiveness.
PMID- 10193401
TI - Renal and hormonal abnormalities in chronic obstructive pulmonary disease (COPD).
PMID- 10193403
TI - Retransplantation in a patient with cystic fibrosis.
AB - A patient with cystic fibrosis is described who requested a third lung
transplant. The medical and ethical issues involved are discussed.
PMID- 10193404
TI - Rifampicin containing antituberculosis medication.
PMID- 10193402
TI - Airway hyperresponsiveness in asthma: not just a matter of airway inflammation.
PMID- 10193405
TI - Intracellular interferon-gamma (IFN-gamma) production in normal children and
children with atopic dermatitis.
AB - A reduction in the in vitro production of IFN-gamma has been consistently
described in atopic dermatitis (AD). Whether this reduction is due to a decrease
in the population of peripheral blood mononuclear cells (PBMC) producing IFN
gamma or reduced IFN-gamma production per cell, or a combination of both is not
clear. We have examined the intracellular production of IFN-gamma in children
with AD and in healthy non-atopic controls. As Staphylococcus aureus colonization
is a feature of childhood AD, and is postulated to contribute to the cutaneous
inflammation in atopic dermatitis, S. aureus and Staphylococcal enterotoxin B
(SEB) were used to activate PBMC. Stimulated PBMC from subjects with AD had
significantly fewer IFN-gamma-containing cells in response to SEB (P < 0.001) and
S. aureus (P < 0.01) than normal non-atopic children. In addition, SEB-stimulated
PBMC from children with AD had less IFN-gamma per cell than normal non-atopic
children (P < 0.01). Reduction in the proportion of cells containing IFN-gamma
was seen in CD4+, CD8+ and natural killer (NK) cells in PBMC from children with
AD. Our findings indicate that reduced production of IFN-gamma observed in
childhood AD is due to both a decrease in the number of IFN-gamma-producing cells
and a reduced amount of IFN-gamma production per cell. Furthermore, we found that
this defect was not confined to CD4+ T cells, suggesting a more generalized
defect in IFN-gamma production in childhood AD.
PMID- 10193406
TI - (1-->3)-beta-D-glucan may contribute to pollen sensitivity.
AB - The amount of (1-->3)-beta-D-glucan in pollen from different plants was evaluated
using the Limulus assay with a specific lysate. The amount ranged from 79 to 1800
ng/10(6) pollen. A calculation of the inhaled dose suggests that the amount of (1
->3)-beta-D-glucan present during periods with a high pollen content in the air
exceeds levels that cause airways inflammation.
PMID- 10193407
TI - Characterization of Epstein-Barr virus (EBV)-infected natural killer (NK) cell
proliferation in patients with severe mosquito allergy; establishment of an IL-2
dependent NK-like cell line.
AB - The clinical evidence of a relationship between severe hypersensitivity to
mosquito bite (HMB) and clonal expansion of EBV-infected NK cells has been
accumulated. In order to clarify the mechanism of EBV-induced NK cell
proliferation and its relationship with high incidence of leukaemias or lymphomas
in HMB patients, we studied clonally expanded NK cells from three HMB patients
and succeeded in establishing an EBV-infected NK-like cell line designated KAI3.
Immunoblotting and reverse transcriptase-polymerase chain reaction (RT-PCR)
analyses revealed that KAI3 cells as well as infected NK cells exhibited an EBV
latent infection type II, where EBV gene expression was limited to EBNA 1 and
LMP1. As KAI3 was established by culture with IL-2, IL-2 responsiveness of
peripheral blood NK cells from patients was examined. The results represented
markedly augmented IL-2-induced IL-2R alpha expression in NK cells. This
characteristic property may contribute to the persistent expansion of infected NK
cells. However, KAI3 cells as well as the NK cells from patients were not
protected from apoptosis induced by either an anti-Fas antibody or NK-sensitive
K562 cells. Preserved sensitivity to apoptosis might explain the relatively
regulated NK cell numbers in the peripheral blood of the patients. To our
knowledge, KAI3 is the first reported NK-like cell line established from patients
of severe chronic active EBV infection (SCAEBV) before the onset of leukaemias or
lymphomas. KAI3 cells will contribute to the study of EBV persistency in the NK
cell environment and its relationship with high incidence of leukaemias or
lymphomas in HMB patients.
PMID- 10193408
TI - Detection of allergen-induced basophil activation by expression of CD63 antigen
using a tricolour flow cytometric method.
AB - In the field of allergy diagnosis, most in vitro functional tests are focused on
basophils. Nevertheless, the very small number of circulating basophils limits
these experiments and their clinical benefit remains controversial. As flow
cytometry is a valuable tool for identifying cell populations, even at low
concentrations, we developed a tricolour flow cytometric method for the study of
allergen-induced basophil activation. Identification of cells was based both on
CD45 expression and on the presence of IgE on the cell surface, since basophils
express high-affinity receptors for IgE (Fc epsilon RI). Cell activation upon
allergen challenge was assessed by the expression of CD63 antigen on the plasma
membrane. Basophil isolation and activation (with the chemotactic peptide formyl
methionyl-leucyl-phenylalanine) were validated in 32 non-allergic patients. In 12
allergic patients, basophil stimulation by a relevant allergen was in most cases
positive (10/12). Furthermore a concentration-dependent hook effect was observed.
Of the allergic and non-allergic patients, none showed non-specific activation
with an irrelevant allergen (specificity 100%). Overall, our preliminary results,
even in a small population, suggest that this is a reliable and valuable method
for the diagnosis of allergies complementing specific allergen IgE and skin test
results. Obviously, additional clinical studies are needed to validate these
first results.
PMID- 10193409
TI - Expression, purification and immunological characterization of the transforming
protein E7, from cervical cancer-associated human papillomavirus type 16.
AB - E7 is the major oncogenic protein produced in cervical cancer-associated human
papillomavirus type 16 (HPV16). This protein was expressed in Escherichia coli as
a glutathione-S-transferase (GST) fusion protein. E7-enriched inclusion bodies
were collected from bacterial lysates, were solubilized in 10 M urea, and the
protein was purified using anion exchange column chromatography. After removal of
endotoxin with serial Triton X-114 extractions, material of high purity (about
90%) was obtained, which is suitable for use in a human clinical trial. This
material was immunogenic, and when used as a vaccine, protected mice against
challenge with an HPV16 E7 DNA transfected tumour cell line. Based on this
observation, the E7GST fusion protein is currently being used in a human clinical
trial of a vaccine against HPV16-induced cervical cancer. This fusion protein
could be cleaved with thrombin to remove the GST fusion part and further purified
by preparative SDS gel electrophoresis to obtain free E7 with > 98% purity.
PMID- 10193410
TI - Anti-mitochondrial flavoprotein autoantibodies of patients with myocarditis and
dilated cardiomyopathy (anti-M7): interaction with flavin-carrying proteins,
effect of vitamin B2 and epitope mapping.
AB - Vitamin B2 and flavin cofactors are transported tightly bound to immunoglobulin
in human serum. We reasoned that anti-mitochondrial flavoprotein autoantibodies
(alpha Fp-AB) present in the serum of patients with myocarditis and
cardiomyopathy of unknown aetiology may form immunoglobulin aggregates with these
serum proteins. However, immunodiffusion and Western blot assays demonstrated
that the flavin-carrying proteins were not recognized by alpha Fp-AB. Apparently
the flavin moiety in the native protein conformation was inaccessible to alpha Fp
AB. This conclusion was supported by the absence of an immunoreaction between the
riboflavin-binding protein from egg white and alpha FP-AB. Intravenous
application of vitamin B2 to rabbits immunized with 6-hydroxy-D-nicotine oxidase,
a bacterial protein carrying covalently attached FAD, did not neutralize alpha Fp
AB which had been raised in the serum of the animals. FAD-carrying peptides
generated from 6-hydroxy-D-nicotine oxidase by trypsin and chymotrypsin treatment
were not recognized by the alpha Fp-AB, but those generated by endopeptidase Lys
were. This demonstrates that the epitope recognized by alpha Fp-AB comprises,
besides the flavin moiety, protein secondary structure elements.
PMID- 10193411
TI - Evidence for control of tumour necrosis factor-alpha (TNF-alpha) activity by TNF
receptors in patients with proliferative diabetic retinopathy.
AB - TNF-alpha has been implicated in the pathogenesis of insulin- dependent diabetes
mellitus (IDDM). At present there are no studies linking serum levels of soluble
TNF receptors (sTNF-R) to the development of diabetic microvascular complications
such as proliferative diabetic retinopathy (PDR), or to the production of TNF
alpha in these patients. We investigated serum levels of sTNF receptors (sTNF-RI
and sTNF-RII) in IDDM patients with or without PDR, and related these to the in
vitro production of TNF-alpha upon activation of whole blood and isolated
mononuclear cells (MNC). We observed higher serum levels of sTNF-RI in IDDM
patients with active (range 945-6630 pg/ml; P = 0.029) or quiescent PDR (range
1675-4970 pg/ml; P = 0.00092) than in individuals with IDDM without retinopathy
(range 657-2617 pg/ml) or healthy controls (range 710-1819 pg/ml; P = 0.0092 and
0.0023, respectively). Increased serum levels of sTNF-RII were also seen in IDDM
patients with active PDR (range 1749-5218 pg/ml; P = 0.034) or quiescent PDR
(range 1494-5249 pg/ml; P = 0.0084) when compared with disease controls (range
1259-4210 pg/ml) or healthy subjects (range 1237-4283 pg/ml). Whole blood
production of biologically active TNF-alpha was lower in PDR patients than in
disease (P = 0.04) and healthy controls (P < 0.005), contrasting with a higher
production of TNF-alpha by lipopolysaccharide (LPS)-activated MNC from PDR
patients (P = 0.013). Inhibition of TNF-alpha by TNF-R in plasma supernatants of
activated blood from PDR patients was demonstrated by increase of TNF-alpha
activity in the presence of anti-TNF-RI and anti-TNF-RII antibodies. These
observations suggest that abnormalities in TNF-alpha production and control may
operate during the development of microvascular complications of diabetes
mellitus.
PMID- 10193412
TI - Inhibitory effects of transforming growth factor-beta (TGF-beta) on certain
functions of intraepithelial lymphocytes.
AB - Human intraepithelial lymphocytes (IEL), CD8+ lymphocytes located between
epithelial cells, are likely to be influenced by the immunosuppressive cytokine,
TGF-beta, secreted by epithelial cells. This study evaluates the effects of TGF
beta on IEL functions. IEL were derived from proximal jejunum of patients
undergoing gastric bypass operations for morbid obesity. Proliferation was
determined by 3H-thymidine incorporation; IL-2 production, by ELISA; expression
of IL-2 receptor, CD2, HML1, CD16, and CD56, by immunofluorescence; binding, by
adherence of radiolabelled cells; and cytotoxicity by 51Cr-release assay. TGF
beta (> or = 1 ng/ml) inhibited the mitosis of IEL to mitogens, IL-7, and stimuli
of the CD2 and CD3 pathways. The blocking effect did not target the activation
events of IL-2 production and receptor generation. Rather, it reduced cell
division after activation when added 24 h after initiating the culture. Antibody
neutralization of naturally occurring TGF-beta increased IEL proliferation to IL
2, but not to the other stimuli. Of the multiple surface markers tested, only CD2
and HML1 expression increased with TGF-beta and decreased with antibody to TGF
beta, although the cytokine and the neutralizing antibody had no effects on IEL
binding to colon cancer. TGF-beta reduced the number of CD56+ IEL and the
lymphokine-activated killing when co-cultured with IL-7 but not with IL-2 or IL
15. TGF-beta inhibits certain IEL functions: the reduction in cell division
rather than activation and a decline in IL-7-mediated lysis of colon cancer due
to a lowering of the number of natural killer cells.
PMID- 10193413
TI - The inflammatory response in CD1 mice shortly after infection with a CagA+/VacA+
Helicobacter pylori strain.
AB - To investigate the early events of Helicobacter pylori infection in a mouse
model, CD1 mice were infected with a type I (CagA+/VacA+) H. pylori strain. Up to
4 weeks after infection the majority of gastric tissue biopsies were positive in
culture. Immunohistochemical analysis showed that inflammatory changes started to
occur after 3 weeks. Four weeks after infection a significant increase in T cells
was observed in the cardia/corpus region of the stomachs of infected mice. These
T cells were CD4+ and CD8+, and they were located in an area with increased
expression of MHC class II antigens. In 50% of the infected mice also an
increased number of mast cells was seen. Furthermore, aggregates of B and T cells
were present in the submucosa. Characterization of cytokines by
immunohistochemistry showed an increase in IL-5-secreting cells in the inflamed
area of the infected stomach. No difference was observed between interferon-gamma
(IFN-gamma)-, IL-4- and IL-10-secreting cells in control and infected mice. These
results suggest that no polarized T-helper cell response was present at this
early phase of infection. Infection with H. pylori also induced a serum response
and especially IgG was increased after 4 weeks of infection. However, no
particular increase in IgG1, IgG2a or IgG3 isotype was observed. Part of the
serum antibodies was directed against lipopolysaccharide (LPS), but no evidence
for anti-Lewis antibodies or antibodies against epitopes on the gastric mucosa
was found.
PMID- 10193415
TI - The modulating effects of proinflammatory cytokines interferon-gamma (IFN-gamma)
and tumour necrosis factor-alpha (TNF-alpha), and immunoregulating cytokines IL
10 and transforming growth factor-beta (TGF-beta), on anti-microbial activity of
murine peritoneal macrophages against Mycobacterium avium-intracellulare complex.
AB - We assessed the roles of proinflammatory cytokines IFN-gamma and TNF-alpha, and
immunoregulatory cytokines IL-10 and TGF-beta in the modulation of the anti
microbial activity of murine peritoneal macrophages against Mycobacterium avium
intracellulare complex (MAIC). First, both IFN-gamma and TNF-alpha significantly
reduced the bacterial growth in macrophages, indicating that these cytokines
participate in up-regulation of macrophage anti-MAIC function. Second, although
MAIC-infected macrophages produced substantial amounts of IL-10 and TGF-beta,
neutralization of endogenous IL-10 and TGF-beta with anti-IL-10 and anti-TGF-beta
antibodies, respectively, did not affect the intracellular growth of MAIC in
macrophages from mice with BcgS (MAIC-susceptible) or BcgI (MAIC-resistant)
genotype, regardless of the virulence of test MAIC strains. The same result was
also obtained for macrophages stimulated with IFN-gamma or TNF-alpha. Third, in
MAIC-infected mice, the growth of organisms at the sites of infection (lungs and
spleens) was not affected by administration of anti-IL-10 or anti-TGF-beta
antibodies. These findings indicate that, in the case of mice, endogenous IL-10
and TGF-beta are essentially ineffective in down-regulating macrophage anti-MAIC
functions not only in vitro but also in vivo.
PMID- 10193414
TI - Reactivation of tuberculosis is associated with a shift from type 1 to type 2
cytokines.
AB - The pattern of cytokines produced by T cells from mice with latent tuberculosis
and during reactivation of tuberculosis was determined. A type 1 cytokine pattern
was observed in T cells isolated from the lung of mice with latent disease.
Reactivation of mycobacterial growth, by activation of the hypothalamic-pituitary
adrenal (HPA) axis, resulted in a shift from a type 1 to a type 2 cytokine
pattern in both CD4 and CD8 T cells. Classification of the T cells based on their
differential expression of CD45 and CD44 showed that the phenotypically different
populations of CD4 and CD8 cells exhibited a type 1 cytokine pattern at latency
and that reactivation of latent tuberculosis was associated with a shift in
cytokines produced by these populations to a type 2 cytokine response. Control of
mycobacterial growth resulted in a return to the type 1 cytokine pattern found
during latent disease.
PMID- 10193416
TI - Reduced naive and increased activated CD4 and CD8 cells in healthy adult
Ethiopians compared with their Dutch counterparts.
AB - To assess possible differences in immune status, proportions and absolute numbers
of subsets of CD4+ and CD8+ T cells were compared between HIV- healthy Ethiopians
(n = 52) and HIV- Dutch (n = 60). Both proportions and absolute numbers of naive
CD4+ and CD8+ T cells were found to be significantly reduced in HIV Ethiopians
compared with HIV- Dutch subjects. Also, both proportions and absolute numbers of
the effector CD8+ T cell population as well as the CD4+CD45RA-CD27- and
CD8+CD45RA-CD27- T cell populations were increased in Ethiopians. Finally, both
proportions and absolute numbers of CD4+ and CD8+ T cells expressing CD28 were
significantly reduced in Ethiopians versus Dutch. In addition, the possible
association between the described subsets and HIV status was studied by comparing
the above 52 HIV- individuals with 32 HIV+ Ethiopians with CD4 counts >
200/microliter and/or no AIDS-defining conditions and 39 HIV+ Ethiopians with CD4
counts < 200/microliter or with AIDS-defining conditions. There was a gradual
increase of activated CD4+ and CD8+ T cells, a decrease of CD8+ T cells
expressing CD28 and a decrease of effector CD8+ T cells when moving from HIV- to
AIDS. Furthermore, a decrease of naive CD8+ T cells and an increase of memory
CD8+ T cells in AIDS patients were observed. These results suggest a generally
and persistently activated immune system in HIV- Ethiopians. The potential
consequences of this are discussed, in relation to HIV infection.
PMID- 10193417
TI - Enhanced expression of CTLA-4 (CD152) on CD4+ T cells in HIV infection.
AB - CTLA-4 (CD152) is a surface molecule of activated T cells with sequence homology
to CD28. Both molecules bind to the same ligands, B7.1 (CD80) and B7.2 (CD86) but
have antagonistic functions. While CD28 is an important costimulator, CTLA-4 has
an essential inhibitory function in maintaining the homeostasis of the immune
system. Down-regulation of CD28 predominantly on CD8+ T cells has been described
in HIV infection, but analysis of CTLA-4 is complicated by its low expression
levels. Here we have used potent signal enhancement to study CTLA-4 on peripheral
blood mononuclear cells (PBMC) during HIV infection. CTLA-4 was expressed only on
T cells. Expression levels were significantly increased selectively on CD4+ T
cells during all stages of HIV infection, while CTLA-4 expression on CD8+ T cells
was always low. In contrast, after stimulation with the mitogen
phytohaemagglutinin (PHA), CTLA-4 levels were strongly increased on T cells from
controls but in T cells from HIV patients this response was severely impaired.
Our data suggest that in HIV infection CD4+ and CD8+ T cells may be less
responsive to B7 costimuli due to two different mechanisms: increase in CTLA-4
expression by CD4+ cells and down-regulation of CD28 by CD8+ cells.
PMID- 10193418
TI - Expression of CD28 and CD38 by CD8+ T lymphocytes in HIV-1 infection correlates
with markers of disease severity and changes towards normalization under
treatment. The Swiss HIV Cohort Study.
AB - The relationship between blood CD8+ T lymphocyte subsets, as defined by CD28 and
CD38 expression, and plasma viraemia and CD4+ T cells in HIV-1 infection was
investigated. In a cross-sectional study of 46 patients with either no or stable
anti-retroviral treatment, there was a strong negative correlation between the
percentage of CD8+CD28- and the percentage of CD4+ T cells (r = -0.75, P <
0.0001), and a positive correlation between absolute numbers of CD8+CD28+ and
CD4+ T cells (r = 0.56, P < 0.0001). In contrast, the expression of CD38 by CD8+
T lymphocytes correlated primarily with plasma viraemia (e.g. the percentage of
CD38+ in CD8bright cells, r = 0.76, P < 0.0001). In the 6 months following triple
therapy initiation in 32 subjects, there was a close correlation between changes
(delta) in CD8+CD28+ or CD8+CD28- and in CD4+ T cells (e.g. delta % CD8+CD28+
versus delta % CD4+, r = 0.37, P = 0.0002; delta % CD8+CD28- versus delta % CD4+,
r = -0.66, P < 0.0001). A marked decline of the number of CD8+ T cells expressing
CD38 was also observed. These results suggest the existence of a T cell
homeostasis mechanism operating in blood with CD4+ and CD8+CD28+ cells on the one
hand, and with CD8+CD28- cells on the other. In addition, the percentage of CD38+
cells in CD8+ cells, generally considered an independent prognostic factor, could
merely reflect plasma viral load.
PMID- 10193419
TI - Anti-phospholipid antibodies and CD5+ B cells in HIV infection.
AB - This cross-sectional study evaluates the correlation between anti-phospholipid
antibodies and CD5+ B cells in 110 patients infected with HIV-1. There were 89.1%
of the patients who had IgG antibodies against cardiolipin and
phosphatidylserine. The prevalence of IgM and IgA antibodies was < 22%. AIDS was
associated with lower frequencies of IgM antibodies against cardiolipin (P =
0.05) and IgG-antibodies against cardiolipin and phosphatidylserine (P = 0.011).
Drug users had higher IgM antibodies against phospholipids than patients from
other risk groups (P = 0.02). A history of thromboembolic events was not
accompanied by higher levels of anti-phospholipid antibodies (P > 0.2). No
correlation between anti-phospholipid antibodies and CD5+ B cells was detected.
Percentage part of CD5+ B lymphocytes was elevated in all patients and absolute
CD4+ T lymphocyte counts and HIV p24 antigen were inversely correlated. In
advanced disease a significant reduction of anti-phospholipid antibodies was
contrasted with persistent elevation of CD5+ B lymphocytes. These observations
may reflect immunological dysfunction involving apoptosis and endothelial damage
rather than polyclonal B cell hyperstimulation. A possible explanation would be
that in HIV infection an increased rate of spontaneous apoptosis in peripheral
blood lymphocytes is accompanied by functional and structural changes of
mitochondria. Therefore, structurally altered mitochondrial phospholipids could
serve as antigen to induce specific humoral immune responses.
PMID- 10193420
TI - Expression of killer inhibitory receptors on cytotoxic cells from HIV-1-infected
individuals.
AB - Dysfunction of cytotoxic activity of T and natural killer (NK) lymphocytes is a
main immunological feature in patients with AIDS, but its basis are not well
understood. It has been recently described that T and NK cell-mediated
cytotoxicity can be regulated by HLA killer inhibitory receptors (KIR). In this
work, we have determined on cytotoxic T cells and NK cells from HIV-1-infected
individuals the expression of the following KIR molecules: p58, p70, and ILT2
(immunoglobulin-like family KIR) as well as CD94 and NKG2A (C-lectin-type family
KIR). With some exceptions, no significant changes were found on the expression
of immunoglobulin-like KIR in either CD8+ or CD56+ cells. Interestingly, the
percentages of CD8+ and CD56+ cells expressing CD94 were significantly increased
in these individuals. We also show that, in vitro, IL-10 up-regulates CD94
expression on CD8+ and CD56+ cells obtained from normal individuals, suggesting
that the augmented expression observed in HIV-infected individuals could be
related to the high levels of IL-10 previously described in HIV-1-infected
individuals.
PMID- 10193421
TI - CD4 depletion in HIV-infected haemophilia patients is associated with rapid
clearance of immune complex-coated CD4+ lymphocytes.
AB - The predominant immunological finding in HIV+ haemophilia patients is a decrease
of CD4+ lymphocytes during progression of the disease. Depletion of CD4+
lymphocytes is paralleled by an increase in the proportion of immune complex
coated CD4+ cells. We examined the hypothesis that the formation of immune
complexes on CD4+ lymphocytes is followed by rapid clearance of immune complex
coated CD4+ lymphocytes from the circulation. In this study, the relationship of
relative to absolute numbers of immune complex-loaded CD4+ blood lymphocytes and
their association with viral load were studied. Two measurements of relative and
absolute numbers of gp120-, IgG- and/or IgM-loaded CD4+ lymphocytes were analysed
in HIV+ and HIV- haemophilia patients, with a median interval of approx. 3 years.
Immune complexes on CD4+ lymphocytes were determined using double-fluorescence
flow cytometry and whole blood samples. Viral load was assessed using NASBA and
Nuclisens kits. Whereas the proportion of immune complex-coated CD4+ lymphocytes
increased with progression of the disease, absolute numbers of immune complex
coated CD4+ lymphocytes in the blood were consistently low. Relative increases of
immune complex-coated CD4+ blood lymphocytes were significantly associated with
decreases of absolute numbers of circulating CD4+ lymphocytes. The gp120 load on
CD4+ blood lymphocytes increased in parallel with the viral load in the blood.
These results indicate that immune complex-coated CD4+ lymphocytes are rapidly
cleared from the circulation, suggesting that CD4+ reactive autoantibodies and
immune complexes are relevant factors in the pathogenesis of AIDS. Relative
increases of immune complex-positive cells seem to be a consequence of both an
increasing retroviral activity as well as a stronger loading with immune
complexes of the reduced number of CD4+ cells remaining during the process of CD4
depletion. The two mechanisms seem to enhance each other and contribute to the
progressive CD4 decrease during the course of the disease.
PMID- 10193422
TI - Heat shock protein 70 (hsp70) as a major target of the antibody response in
patients with pulmonary cryptococcosis.
AB - Cryptococcus neoformans causes infection in individuals with defective T cell
function, such as AIDS, as well as without underlying disease. It has been
suggested that humoral as well as cellular immunity might play an important role
in the immune response to C. neoformans infection. We have recently shown, using
immunoblotting, that the 70-kD hsp family of C. neoformans was the major target
molecule of the humoral response in murine pulmonary cryptococcosis. In this
study we also used immunoblotting to define the antibody responses in the sera of
24 patients with pulmonary cryptococcosis: 21 proven and three suspected
diagnoses. Anti-C. neoformans hsp70 antibody was detected in 16 of 24 (66.7%)
patients with pulmonary cryptococcosis. Fourteen of 17 (82.3%) patients with high
antigen titres (> or = 1:8) and two of seven (28.6%) patients with low titres (<
or = 1:4) had detectable levels of anti-hsp70 antibody. Sera from patients
positive for anti-hsp70 antibody showed high titres in the Eiken latex
agglutination test for the detection of serum cryptococcal antigen. Our results
indicate that the 70-kD hsp family from C. neoformans appears to be a major
target molecule of the humoral response, not only in murine pulmonary
cryptococcosis, but also in human patients with pulmonary cryptococcosis.
PMID- 10193423
TI - Candida albicans suppresses nitric oxide (NO) production by interferon-gamma (IFN
gamma) and lipopolysaccharide (LPS)-stimulated murine peritoneal macrophages.
AB - We examined the in vitro effect of Candida albicans on NO production by
macrophages. Candida albicans suppressed not only NO production but also
expression of inducible NO synthase (iNOS) mRNA by murine IFN-gamma and bacterial
LPS-stimulated peritoneal macrophages. The suppression was not associated with
inhibition but rather stimulation of IL-1 beta production. This effect was
observed when more than 1 x 10(3)/ml of Candida albicans were added to macrophage
cultures (1 x 10(6) cells/ml) and reached a maximal level at 1 x 10(6)/ml. The NO
inhibitory effect of Candida albicans was mediated predominantly by as yet
unidentified soluble factor(s) and to a lesser extent by direct contact. In
addition, heat- or paraformaldehyde-killed Candida albicans did not show this
inhibitory activity. Culture supernatant of Candida albicans also inhibited NO
production by activated macrophages in a dose-dependent manner, and increased IL
1 beta production. Finally, the inhibitory effect was not mediated by IL-10 and
transforming growth factor-beta (TGF-beta), since neutralizing antibodies to
these cytokines did not influence Candida albicans-induced reduction in
macrophage NO production. Our results suggest that Candida albicans may evade
host defence mechanism(s) through a soluble factor-mediated suppression of NO
production by stimulated macrophages, and that the effect is independent of
production of immunosuppressive cytokines such as IL-10 and TGF-beta.
PMID- 10193424
TI - Asymptomatic Borrelia-seropositive individuals display the same incidence of
Borrelia-specific interferon-gamma (IFN-gamma)-secreting cells in blood as
patients with clinical Borrelia infection.
AB - Borrelia Lyme disease is a complex disorder that sometimes becomes chronic. There
are contradictory reports of experimental Borrelia infections regarding which
type of T cell cytokine responses, i.e. Th1 or Th2, are needed to eradicate the
Borrelia spirochaetes. In human borreliosis a predominance of Borrelia-specific
Th1-like responses has been shown. In this study, spontaneous, as well as
Borrelia-specific, secretion of IFN-gamma (Th1) and IL-4 (Th2) in Borrelia
seropositive healthy asymptomatic individuals (n = 17) was investigated in
peripheral blood by a sensitive ELISPOT assay, and compared with previously
reported responses in patients with clinical Borrelia infection (n = 25). The
seropositive asymptomatic individuals displayed the same predominance of Borrelia
specific IFN-gamma-secreting cells as the patients with clinical Borrelia
infection. Interestingly, the proportion of spontaneously IL-4-secreting cells,
reflecting the unstimulated in vivo secretion, was lower in the seropositive
asymptomatic individuals compared with patients with chronic Borrelia infections
(n = 13, P = 0.02), whereas no such difference was found compared with subacute
Borrelia infections (n = 12). These findings indicate that IFN-gamma secretion
alone is not sufficient to eliminate Borrelia spirochaetes in humans, although
IFN-gamma may still have a beneficial role in borreliosis acting in concert with
other mechanisms.
PMID- 10193425
TI - Serum cytokine detection in the clinical follow up of patients with cystic
echinococcosis.
AB - The relation of serum cytokine levels and outcome of chemotherapy was evaluated
in 15 patients with cystic echinococcosis. Serum IL-4, IL-10 and interferon-gamma
(IFN-gamma) concentrations were determined by ELISA before and after a 3-month
course of albendazole treatment: at least one serum sample per patient from 13
patients (87%) contained measurable amounts of IL-4; samples from five patients
(33%) measurable amounts of IL-10 and samples from only two patients (13%)
measurable amounts of IFN-gamma. Clinical assessment at 1 year after the end of
therapy showed that 11 of the 15 patients had responded clinically. Seven of
these patients had lower IL-4 serum concentrations, two had unchanged and two
undetectable amounts (pre- versus post-therapy, n = 11, P = 0.008). Conversely,
of the patients who did not respond, three had higher and one patient unchanged
serum IL-4 concentrations. Serum IL-10 10 levels also decreased in all patients
who responded (3/5) and increased in all patients who did not (2/5). No
association was found between cytokine concentrations and cyst characteristics or
antibody levels. Overall these data suggest that serum IL-4 detection may be
useful in the follow up of patients with cystic echinococcosis.
PMID- 10193426
TI - HBV-specific immune defect in chronic hepatitis B (CHB) is correlated with a
dysregulation of pro- and anti-inflammatory cytokines.
AB - The aim of this study was to examine the immunomodulating effects of rhIL-12 on
the immune response induced by hepatitis B virus (HBV) antigens in clinical
subgroups of patients with HBV infection. Peripheral blood mononuclear cells
(PBMC) of 80 patients were stimulated with HBsAg, HBcAg, pre-S1Ag and tetanus
toxoid in the absence or presence of IL-12 (0.01, 0.1 and 1 ng/ml). Stimulation
by anti-CD3+ anti-CD28 and lipopolysaccharide (LPS) were used as controls.
Proliferation and cytokine production were determined by 3H-thymidine uptake and
ELISA after 72 h. After stimulation with HBV antigens only, production of tumour
necrosis factor-alpha (TNF-alpha) or IL-10 was observed in all patients, while
interferon-gamma (IFN-gamma) was detectable in only 27 patients. After
costimulation with IL-12 and HBV antigens, however, large amounts of IFN-gamma
were found in all patients, while HBV-induced IL-10 production remained mostly
unchanged. When clinical subgroups including patients with compensated liver
cirrhosis were compared, PBMC from patients with HBeAg+ hepatitis showed the
lowest capacity to produce IFN-gamma after HBV antigen-positive IL-12. These data
suggest that the ability of IL-12 to enhance IFN-gamma production against HBV
antigens is correlated with the presence of HBeAg and is not impaired in patients
with advanced liver disease. In addition, IL-12 and IL-10 production by antigen
presenting cells may be a critical factor that determines the efficacy of the
immune response against the hepatitis B virus.
PMID- 10193427
TI - Imbalance of IL-1 beta and IL-1 receptor antagonist mRNA in liver tissue from
hepatitis C virus (HCV)-related chronic hepatitis.
AB - Increased levels of IL-1 beta and IL-1 receptor antagonist (IL-1Ra) have been
found in serum of patients with chronic liver diseases, although their expression
in liver tissue has not been extensively investigated. The aim of this study was
therefore to examine the relationship between IL-1 beta and IL-1Ra at tissue
level in patients with HCV-related chronic active hepatitis (CAH) of varying
degrees of severity. IL-1 beta and IL-1Ra mRNA expression was investigated by
semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) in 31
patients with CAH of varying severity (classified as minimal/mild in 13 cases and
moderate/severe activity in 18 cases) and in 12 control subjects. Quantitative
evaluation of IL-1 beta and IL-1Ra corresponding bands was performed by
densitometric image analysis, and expressed in arbitrary units. The 12 controls
expressed a similar pattern with a mean IL-1 beta/IL-1Ra ratio of 1.03 (1.03 +/-
0.15 (mean +/- s.e.m.), median 0.92, range 0.71-1.45). Minimal/mild activity CAH
showed a prevalence of IL-1Ra mRNA expression (1.14 +/- 0.64, median 0.43, range
0-8.75) when compared with controls (0.27 +/- 0.04, median 0.23, range 0.11-0.45)
and with moderate/severe activity CAH (0.20 +/- 0.04, median 0.12, range 0-0.67;
P = 0.01). Since IL-1 beta expression was similar in the three groups, a
significantly different IL-1 beta/IL-1Ra ratio emerged between controls, patients
with moderate/severe CAH (2.22 +/- 0.48, median 2.76, range 0-6.12) and those
with minimal/mild activity CAH (0.62 +/- 0.15, median 0.5, range 0-1.58, P =
0.005). Patients with higher grades of fibrosis showed a higher IL-1 beta/IL-1Ra
ratio (2.49 +/- 0.56, median 2.15, range 0.35-6.12) in comparison with lower
grade fibrosis (1.06 +/- 0.30, median 0.59, range 0.03-4.50) and control patients
(P = 0.01). These results suggest that an imbalance between IL-1 beta and IL-1Ra,
at the tissue level, may contribute to the pathogenesis and the activity of
chronic active hepatitis C.
PMID- 10193428
TI - Cytokine flow cytometry differentiates the clinical status of multiple sclerosis
(MS) patients.
AB - In this study we have examined intracellular cytokines in peripheral blood
mononuclear cells (PBMC) of MS patients by flow cytometry (cytokine flow
cytometry). MS progressive patients showed an increased number of cells producing
interferon-gamma (IFN-gamma) after activation with phorbol 12-myristate 13
acetate and ionomycin, compared with patients with clinically inactive forms (P <
0001) and with healthy controls (P = 0001). These cells belonged to the CD4+ and
CD8+ subsets in similar proportions. Clinically inactive patients showed a lower
level of cells producing IL-2 than controls (P = 0.03) and active MS patients (P
= 0.03). Most IL-2-producing cells were CD4+ lymphocytes, although a small part
of the IL-2 was also produced by CD8+ cells. The percentage of cells producing
simultaneously IL-2 and IFN-gamma was increased in active MS and they were mainly
CD4+ lymphocytes. No differences in the production of IL-4 were observed between
groups. However, we found an increased IL-10 production in clinically active MS
patients (P = 0.03). Treatment with IFN-beta of active MS patients showed lower
levels of cytokines when compared with untreated MS patients. This methodological
approach could help in the follow up and therapeutic monitoring of MS patients.
PMID- 10193429
TI - Alzheimer's beta-amyloid peptides can activate the early components of complement
classical pathway in a C1q-independent manner.
AB - beta-Amyloid (beta-A) accumulates in the brain of patients with Alzheimer's
disease (AD) and is presumably involved in the pathogenesis of this disease, on
account of its neurotoxicity and complement-activating ability. Although assembly
of beta-A in particular aggregates seems to be crucial, soluble non-fibrillar
beta-A may also be involved. Non-fibrillar beta-A does not bind C1q, so we
investigated alternative mechanisms of beta-A-dependent complement activation in
vitro. On incubation with normal human plasma, non-fibrillar beta-A 1-42, and
truncated peptide 1-28, induced dose-dependent activation of C1s and C4, sparing
C3, as assessed by densitometric analysis of immunostained membrane after SDS
PAGE and Western blotting. The mechanism of C4 activation was not dependent on
C1q, because non-fibrillar beta-A can still activate C1s and C4 in plasma
genetically deficient in C1q (C1qd). In Factor XII-deficient plasma (F.XIId) the
amount of cleaved C4 was about 5-10% less that in C1qd and in normal EDTA plasma;
the reconstitution of F.XIId plasma with physiologic concentrations of F.XII
resulted in an increased (8-15%) beta-A-dependent cleavage of C4. Thus our
results indicate that the C1q-independent activation of C1 and C4 can be
partially mediated by the activation products of contact system. Since the
activation of contact system and of C4 leads to generation of several humoral
inflammatory peptides, non-fibrillar beta-A might play a role in initiating the
early inflammatory reactions leading to a multistep cascade contributing to
neuronal and clinical dysfunction of AD brain.
PMID- 10193430
TI - Humoral immune responses in periodontal disease may have mucosal and systemic
immune features.
AB - The humoral immune response, especially IgG and IgA, is considered to be
protective in the pathogenesis of periodontal disease, but the precise mechanisms
are still unknown. Immunoglobulins arriving at the periodontal lesion are from
both systemic and local tissue sources. In order to understand better the local
immunoglobulin production, we examined biopsy tissue from periodontitis lesions
for the expression of IgM, IgG, IgA, IgE and in addition the IgG and IgA
subclasses and J-chain by in situ hybridization. Tissues examined were
superficial inflamed gingiva and the deeper granulation tissue from periodontal
sites. These data confirm that IgM, and IgG and IgA subclass proteins and J-chain
can be locally produced in the periodontitis tissues. IgG1 mRNA-expressing cells
were predominant in the granulation tissues and in the gingiva, constituting
approx. 65% of the total IgG-expressing plasma cells. There was a significantly
increased proportion of IgA-expressing plasma cells in the gingiva compared with
the granulation tissue (P < 0.01). Most of the IgA-expressing plasma cells were
IgA1, but a greater proportion expressed IgA2 mRNA and J-chain mRNA in the
gingival tissues (30.5% and 7.5%, respectively) than in the periodontal
granulation tissues (19% and 0-4%, respectively). The J-chain or dimeric IgA2
expressing plasma cells were located adjacent to the epithelial cells, suggesting
that this tissue demonstrates features consistent with a mucosal immune response.
Furthermore, we were able to detect the secretory component in gingival and
junctional epithelial cells, demonstrating that the periodontal epithelium shares
features with mucosal epithelium. In contrast, deeper tissues had more plasma
cells that expressed IgM, and less expressing IgA, a response which appears more
akin to the systemic immune response. In conclusion, this study suggests that
immune mechanisms involved in the pathogenesis of periodontitis may involve
features of both the mucosal and systemic immune systems, dependent on tissue
location.
PMID- 10193431
TI - Enhanced expression of L-selectin on peripheral blood lymphocytes from patients
with IgA nephropathy.
AB - To investigate the homing characteristics of T and B lymphocytes which could
explain the abnormal partition of IgA-producing cells in tonsils and bone marrow
from patients with IgA nephropathy (IgAN), the expression of leucocyte adhesion
molecules (CD11a, CD29, CD49d, CD62L, CD31) was assessed using flow cytometry on
peripheral blood leucocytes from patients with biopsy-proven IgAN and controls.
Higher proportions of T and B lymphocytes expressing higher amounts of L
selectin, as well as higher proportions of B cells expressing more CD31 were
evidenced in IgAN patients. Conversely, serum levels of sCD62L were not different
from controls, but significantly higher than serum levels in patients suffering
from other renal diseases. We hypothesize that this over-expression of CD62L and
CD31 may be involved in an enhanced efficiency of lymphoid cells homing to
lymphoid tissues in this disease.
PMID- 10193432
TI - Disparate T cell requirements of two subsets of lupus-specific autoantibodies in
pristane-treated mice.
AB - Intraperitoneal injection of pristane induces a lupus-like disease in BALB/c and
other non-autoimmune mice characterized by autoantibody production and the
development of immune complex disease closely resembling lupus nephritis. Two
subsets of autoantibodies are induced by pristane: IgG anti-DNA DNA and
chromatin autoantibodies are strongly IL-6-dependent, whereas IgG anti-nRNP/Sm
and -Su antibodies are not. The present studies were carried out to examine the
role of T cells in establishing this dichotomy between the production of anti
nRNP/Sm/Su versus anti-DNA/chromatin autoantibodies. Autoantibody production and
renal disease were evaluated in athymic (nude) mice treated with pristane. BALB/c
nu/nu mice spontaneously developed IgM and IgG anti-single-stranded (ss)DNA and
chromatin, but not anti-nRNP/Sm or -Su, autoantibodies. Pristane treatment
increased the levels of IgG anti-chromatin antibodies in nu/nu mice, but did not
induce production of anti-nRNP/Sm or -Su antibodies. In contrast, BALB/c nu/+ and
+/+ control mice did not spontaneously produce autoantibodies, whereas anti
nRNP/Sm and -Su autoantibodies were induced by pristane in approx. 50% of nu/+
and +/+ mice and anti-DNA/chromatin antibodies at lower frequencies. Nude mice
spontaneously developed mild renal lesions that were marginally affected by
pristane, but were generally milder than the lesions developing in pristane
treated nu/+ and +/+ mice. The data provide further evidence that two distinct
pathways with different cytokine and T cell requirements are involved in
autoantibody formation in pristane-induced lupus. This dichotomy may be relevant
to understanding differences in the regulation of anti-DNA versus anti-nRNP/Sm
autoantibodies in systemic lupus erythematosus, as well as the association of
anti-DNA, but not anti-nRNP/Sm, with lupus nephritis.
PMID- 10193433
TI - Monocyte activation in rheumatoid arthritis (RA): increased integrin, Fc gamma
and complement receptor expression and the effect of glucocorticoids.
AB - The aim of this work was to study the expression of beta 1- and beta 2-integrins,
CR1, CD44 and Fc gamma receptors on peripheral blood monocytes in RA. The
expression of these receptors was measured by flow cytometry, before and after
treatment with low-dose prednisolone. Expression of the same receptors was also
measured before and after treatment with metyrapone, a substance that inhibits
the synthesis of cortisol in the adrenals. The expression of the beta 2-integrins
CD11a, CD11b and CD18, of CD35 (CR1), and of Fc gamma RII and Fc gamma RI (CD32
and CD64) on monocytes was elevated in the RA patients compared with healthy
controls, while the expression of the beta 1-integrins (CD29, CD49d, CD49f) was
unaffected. A significant correlation between monocyte expression of CD64 and C
reactive protein (CRP), and blood platelet count, respectively, was found in the
group of patients with RA. After 4-6 weeks of treatment with low-dose
prednisolone, the expression on the monocytes of CD11a, CD11b, CD18, CD35, CD32
and CD64 was normalized. A significant correlation (r = 0.64, P = 0.02) was found
between the decrease in expression of CD11b and clinical improvement after
prednisolone treatment. Two days of metyrapone treatment, which significantly
lowered the serum cortisol levels, elevated the expression of CD35 and CD49f.
Priming of peripheral monocytes seems to be one of the mechanisms behind the
recruitment of monocytes to the rheumatoid synovium. One reason for the good
clinical effects of prednisolone in RA could be a down-regulation of adhesion and
phagocytosis receptors on monocytes.
PMID- 10193434
TI - Antibodies to adult human endothelial cells cross-react with oxidized low-density
lipoprotein and beta 2-glycoprotein I (beta 2-GPI) in systemic lupus
erythematosus.
AB - Cardiovascular manifestations are common in systemic lupus erythematosus (SLE).
Oxidized low-density lipoprotein (oxLDL) is implicated in cardiovascular disease,
especially atherosclerosis, and cross-reacts with antibodies to cardiolipin
(aCL). beta 2-GPI is a plasma protein participating in the coagulating cascade,
and is also cofactor for aCL, and some aCL have been shown to be directed against
beta 2-GPI and/or complexes between beta 2-GPI and phospholipids.
Lysophosphatidylcholine (LPC) is a phospholipid present both in oxLDL and in
damaged endothelium, and we recently showed that LPC is involved in the
antigenicity of oxLDL. Antibodies to endothelial cells (aEC) correlate with
diseases activity in SLE and vasculitis, and we recently showed that aEC are
enhanced in cardiovascular disease such as borderline hypertension and early
atherosclerosis. aEC were determined using EC from adult V. Saphena Magna.
Antibody levels were determined by ELISA. aEC of IgG type were enhanced in 184
patients with SLE compared with 85 healthy controls. There was a close
correlation between aoxLDL, aCL, aLPC, a beta 2-GPI and aEC. Binding of sera to
EC was competitively inhibited by beta 2-GPI, LPC and oxLDL. Taken together, the
data indicate that EC share antigenic epitopes with beta 2-GPI and with oxLDL,
especially LPC. Phospholipids in EC membranes may thus be antigenic epitopes.
beta 2-GPI may bind to these phospholipids, and become an autoantigen. LPC is
formed by oxidation of phospholipids and/or proinflammatory factors leading to
activation of phospholipase A2, and the findings indicate the potential role of
both lipid oxidation and phospholipase A2 in SLE.
PMID- 10193435
TI - Anti-endothelial cell antibodies in systemic vasculitis and systemic lupus
erythematosus (SLE): effects of heat inactivation on binding and specificity.
AB - Heating sera is used to inactivate complement but may affect the binding
characteristics of autoantibodies. We studied the effect of heating sera from
patients with systemic vasculitides and SLE on antibody binding to cultured human
umbilical vein endothelial cells. Sera from 32 patients with systemic
vasculitides, eight with SLE and 10 healthy controls were studied for anti
endothelial cell antibodies (AECA) using an ELISA before and after heating sera
to 56 degrees C for 30 min. The median (range) AECA binding index in the patient
group increased from 20% (0-153%) to 71.5% (10-259%) (P < 0.0001). The AECA
binding index in the control group also increased from 14% (0-52%) to 90% (42
154%) (P < 0.0001). The increased binding was unaffected by the addition of fresh
complement or removal of immune complexes and the increased binding after heating
persisted even after cooling to 4 degrees C. Specificity experiments showed that
after heating, the binding specificity of sera was lost. Removal of
immunoglobulin with Protein A abolished the increased binding seen after heating.
Heating sera increases AECA binding in both patient and control sera. The
mechanism is probably non-specific damage to the immunoglobulin molecule, and
heating sera should thus be avoided.
PMID- 10193436
TI - Conformationally altered beta 2-glycoprotein I is the antigen for anti
cardiolipin autoantibodies.
AB - Anti-cardiolipin autoantibodies (aCL) induce thrombosis and recurrent fetal
death. These antibodies require a 'cofactor', identified as beta 2-glycoprotein I
(beta 2-GPI), to bind phospholipids. We show here that aCL can bind beta 2-GPI in
the absence of phospholipid. Binding of aCL to beta 2-GPI is dependent upon the
beta 2-GPI being immobilized on an appropriate surface including cardiolipin,
irradiated polystyrene and nitrocellulose membrane. This effect cannot be
explained by increased antigen density of beta 2-GPI immobilized on these
surfaces. Rather, conformational changes that occur following the interaction of
beta 2-GPI with phospholipid render this protein antigenic to aCL. Liquid-phase
beta 2-GPI was not antigenic for aCL. Thus, aCL cannot bind circulating beta 2
GPI. These findings may explain why patients with aCL can remain healthy for many
years but then undergo episodes of thrombosis or fetal loss without changes in
their circulating aCL profile, as the triggering event for these pathologies can
be predicted to be one that renders beta 2-GPI antigenic for aCL.
PMID- 10193437
TI - Glucocorticoids modulate the development of dendritic cells from blood
precursors.
AB - Dendritic cells (DC) are professional antigen-presenting cells, capable of
priming naive T cell responses. Glucocorticoids (GC) are frequently used in
asthmatic patients. In this study we describe the effects of GC on the
development and function of monocyte-derived DC (MoDC) in vitro and in vivo.
Monocytes from healthy individuals were isolated and incubated with granulocyte
macrophage colony-stimulating factor (GM-CSF) and IL-4 for 6 days, to induce
maturation into MoDC. To study the role of GC on DC differentiation in vitro
cells were incubated with dexamethasone at different stages of MoDC development.
At day 6 cells were characterized phenotypically by flow cytometry and
functionally in an allogeneic mixed leucocyte reaction. To study the effect of GC
in vivo patients with mild/moderate atopic asthma were selected. In one group no
GC were used, whereas the other group used inhalation GC. MoDC from these
patients were generated as described above and tested functionally. Incubation of
MoDC or its peripheral blood precursors with dexamethasone decreased the
accessory potency dose-dependently. The functional differences could not be
explained by the changes in the expression of MHC II and the costimulatory
molecules CD40 and CD86. The relevance of this mechanism was confirmed for the in
vivo situation as well. MoDC from patients using inhalation GC showed a decreased
accessory potency. These data suggest a modulatory effect of GC therapy at the
level of the peripheral blood monocyte. The results indicate that GC influence DC
development and function in vitro as well as in vivo.
PMID- 10193439
TI - Asthma, viruses, and nitric oxide.
AB - Over the last two decades there has been a worldwide increase in the morbidity
and mortality associated with asthma, a chronic inflammatory disease of the
airways. There is a growing body of evidence that suggests there is an
association between upper respiratory viral infections, particularly rhinovirus
infections, and asthma exacerbations. Virally induced airways hyperreactivity has
been associated with elevated numbers of inflammatory cells in the bronchial
mucosa. Upon virus infection, respiratory epithelial cells produce
proinflammatory cytokines, including IL-6, IL-8, RANTES, and GM-CSF, which could
contribute to the increased inflammatory cell recruitment noted in the airways.
Whether or not a viral infection triggers an asthma attack may depend upon many
factors, including the types of inflammatory cells recruited to the airways, the
viral load, and variations in the host antiviral response. There is evidence to
support the idea that eosinophils from asthmatic and symptomatic atopic subjects
may be primed to respond to chemotactic cytokines produced by infected epithelial
cells. Rhinovirus infections may therefore enhance airway eosinophilia in
asthmatics, leading to airway hyperresponsiveness and impaired pulmonary
function. Nitric oxide is a potent inhibitor of both rhinovirus-induced cytokine
production and viral replication and may play an important role in the host
response to viral infections. Based upon these observations, we speculate that
nitric oxide donors may represent a novel therapeutic approach for the treatment
of rhinovirus infections and viral exacerbations of asthma.
PMID- 10193440
TI - QT interval and QT dispersion before and after diet therapy in patients with
simple obesity.
AB - To evaluate whether a disordered QT interval and its dispersion in obese
patients, if any, may be improved by therapeutic weight reduction, 36 obese
patients admitted to our university hospital were examined over a 5-year period
from April 1, 1992 to March 31, 1997. Participants included 18 males and 18
females whose mean age +/- SD was 28 +/- 9 and 33 +/- 14 years, respectively, and
whose mean body mass index +/- SD was 35 +/- 5 and 38 +/- 6 kg/m2, respectively.
Thirty-six control patients were matched in age and gender with the obese
patients. All the obese patients were treated with behavioral therapy together
with very-low-calorie conventional Japanese diet (VLCD: 370 kcal/day). A standard
12-lead electrocardiogram (ECG) revealed longer maximum (445 +/- 32 msec, mean +/
SD) and minimum (388 +/- 29 msec) heart rate corrected QT intervals (QTc
intervals) in the obese group than in the control group (P < 0.0001 for each).
QTc dispersion, defined as the difference between maximum and minimum QTc
intervals derived from 12-lead ECG, was greater in the obese group (57 +/- 19
msec) than in the control group (32 +/- 13 msec) (P < 0.0001). Both the maximum
and minimum QTc intervals in the obese patients were shortened, respectively, to
434 +/- 28 msec and 377 +/- 29 msec (P < 0.05 for each) with no significant
change in either QTc dispersion, QRS voltage, or QRS duration following weight
reduction. The coefficient value from the linear regression line between QT
interval and RR interval in the obese group was less than in the control group.
Together, the results show that obesity per se causes both a prolongation of QTc
interval and an increase in QTc dispersion, and that weight reduction improves
the prolonged QTc interval observed in obese patients.
PMID- 10193438
TI - Joint British recommendations on prevention of coronary heart disease in clinical
practice. British Cardiac Society, British Hyperlipidaemia Association, British
Hypertension Society, endorsed by the British Diabetic Association.
PMID- 10193441
TI - Median eminence lesions reveal separate hypothalamic control of pulsatile
follicle-stimulating hormone and luteinizing hormone release.
AB - The effects of hypothalamic lesions designed to destroy either the anterior
median eminence (ME) or the posterior and mid-ME on pulsatile release of follicle
stimulating hormone (FSH) and luteinizing hormone (LH) were determined in
castrated male rats. In sham-operated animals, mean plasma FSH concentrations
rose to peak at 10 min after the onset of sampling, whereas LH declined to a
nadir during this time. In the final sample at 120 min, the mean FSH
concentrations peaked as LH decreased to its minimal value. In rats with anterior
ME lesions, there was suppression of LH pulses with continuing FSH pulses in 12
of 21 rats. On the other hand, in animals with posterior to mid-ME lesions, 3 out
of 21 rats had elimination of FSH pulses, whereas LH pulses were maintained.
Fifteen of 42 operated rats had complete ME lesions, and pulses of both hormones
were abolished. The remaining 12 rats had partial ME lesions that produced a
partial block of the release of both hormones. The results support the concept of
separate hypothalamic control of FSH and LH release with the axons of the
putative FSH-releasing factor (FSHRF) neuronal system terminating primarily in
the mid- to caudal ME, whereas those of the LHRH neuronal system terminate in the
anterior and mid-median eminence. We hypothesize that pulses of FSH alone are
mediated by release of the FSHRF into the hypophyseal portal vessels, whereas
those of LH alone are mediated by LHRH. Pulses of both gonadotropins
simultaneously may be mediated by pulses of both releasing hormones
simultaneously. Alternatively, relatively large pulses of LHRH alone may account
for simultaneous pulses of both gonadotropins since LHRH has intrinsic FSH
releasing activity.
PMID- 10193442
TI - A genetic developmental model of iron deficiency: biological aspects.
AB - Numerous studies have demonstrated the negative impact of iron deficiency on
growth and development. The present study expands on the published literature by
exploring the role of genetics and developmental timing on the impact of iron
deficiency on development in two strains of mice. Growth rates, organ weights,
and hematological responses to an iron-deficient diet differed by strain and sex.
The results from this study provided novel insight into iron metabolism and the
impact of iron deficiency in C57 and DBA strains of mice. Future studies should
continue to examine the contributions of both genetics and sex to the development
of iron deficiency.
PMID- 10193444
TI - Survival and lung pathology of mouse models of Hermansky-Pudlak syndrome and
Chediak-Higashi syndrome.
AB - Hermansky-Pudlak Syndrome (HPS), a recessively inherited disease in humans,
affects the biosynthesis/processing of the related intracellular organelles:
lysosomes, melanosomes, and platelet dense granules. The disease is multigenic in
both humans and mice where 14 separate genes have been demonstrated to be
causative. Patients often die prematurely with severe lung abnormalities.
Patients with the related Chediak-Higashi Syndrome (CHS) likewise have
significantly reduced life spans. Long-term survival and lung histomorphology
were analyzed in a pilot experiment involving several genetically defined singly
and doubly mutant mouse HPS mutants and the beige CHS mutant to determine whether
these parameters are altered in the mouse models. The mutants differed widely in
both longevity and lung architecture. Mice doubly homozygous for the pale ear and
ruby eye or for the muted and pearl genes had the shortest life spans with none
surviving the two-year experimental duration. Life spans were similarly severely
reduced in the beige and gunmetal mutants. Intermediate life spans were apparent
in the pearl, pallid, and cocoa mutants whereas minimal effects were noted in
ruby eye, muted, light ear, and cocoa mutants. Enlarged air spaces were noted in
histologic sections of lungs of several of the mutants. For the most part, the
severity of lung abnormalities was inversely proportional to the long-term
survival of these various mutants, suggesting that lung pathology may contribute
to mortality, as has been suggested for human HPS patients.
PMID- 10193443
TI - Genotype and diet effects in lean and obese Zucker rats fed either safflower or
coconut oil diets.
AB - Previously we reported that suckling lean heterozygous (FA/fa) Zucker rats had a
number of adipose tissue measurements intermediate between those of homozygous
lean (FA/FA) and obese (fa/fa) rats. However, in young adult male rats maintained
on a low-fat diet, these differences were no longer apparent (i.e., values for
the two lean genotypes were similar). In the present study we determined whether
the heterozygous effect of the "fa" gene was dependent on the consumption of a
high-fat diet. Mother rats were fed high-fat diets containing either safflower
(SOD) or coconut (COD) oil throughout mating and lactation. Homozygous lean male
and female rats were bred, as well as obese male and lean heterozygous female
rats. Suckling rats were studied at 17 days of age. Additional male rats were
maintained on the same diet as their mothers until 11-12 weeks of age. Obese
suckling rats had higher body weights than lean pups. Inguinal fat pad weights
and pad-to-body weight ratios followed the pattern of obese greater than lean
(FA/fa) pups that were greater than lean (FA/FA) pups. A similar relationship was
found for adipose tissue lipogenic enzyme activities. At 11-12 weeks of age,
measurements followed the general pattern of obese rats having greater values
than lean rats (i.e., FA/fa = FA/FA). SOD-fa/fa rats had higher hepatic lipogenic
enzyme activities than COD-fa/fa rats. In addition, SOD rats had higher fat cell
numbers than COD rats. These results suggest that specific fatty acids can alter
adipocyte proliferation and/or differentiation in vivo. In addition, there
appears to be a defect of fatty acid regulation in livers of genetically obese
rats. The heterozygous effect of the "fa" gene in suckling Zucker rats was
confirmed. However, high-fat feeding did not result in a heterozygous effect in
young adult lean male rats. We will next evaluate the role of sex on this effect.
PMID- 10193445
TI - Effect of pregnancy-specific beta 1-glycoprotein on the development of
preimplantation embryo.
AB - The objective of this study is to test the hypothesis that members of the
pregnancy-specific beta 1-glycoprotein (PSG) family enhance the growth and
maturation of embryos. cDNA encoding two members of the PSG family, namely PSG1
and PSG3, were expressed in Chinese Hamster Ovary (CHO) cells with the expression
vector pH beta APr-1-neo. Two-cell stage mouse embryos were co-cultured in a two
chamber system with CHO cells expressing either recombinant PSG1 (rPSG1) or PSG3
(rPSG3) in the presence and absence of neutralizing PSG antibodies. The cleavage
and maturation stage of the embryos was assessed at 12-hr intervals. Mouse
embryos co-cultured with transfectants expressing rPSG1 showed a significant
enhancement of cleavage and maturation rate compared to controls with P < 0.005
0.004. In co-cultures with CHO cells expressing rPSG3, no significant difference
from the controls was observed in the early stage of development until late
blastocyst formation. At that stage, there was a statistically significant
enhancement of development by rPSG3 when compared to controls with P < 0.001.
These results suggest that PSG1 and PSG3 exhibit embryotropic activity at
different stages of development in the mouse model.
PMID- 10193447
TI - Effects of ethacrynic acid on intraocular pressure of anesthetized rats.
AB - Ethacrynic acid (ECA) lowers intraocular pressure (i.o.p.) by an effect usually
ascribed to increased drainage of aqueous humor by the trabecular meshwork. Here,
we describe the effects of a continuous 2-hr intracameral infusion of balanced
salt solution (BSS), with or without 2 mM ECA (sodium salt), on IOP of
pentobarbital anesthetized rats. The infusion was divided into a constant (0.05
microliter/min) and a periodic (0.25 microliter/min) component that cycled 4 min
on then 4 min off. This permitted the calculation of dynamic changes in resistive
(trabecular and uveoslceral drainage) and nonresistive (aqueous synthesis,
episcleral venous pressure) components of IOP by fitting a second-order transfer
function to the responses. ECA markedly blunted the BSS-induced rise in IOP (P <
0.01). The rise in resistive mechanisms (ocular impedance) was transiently
blunted by ECA (P < 0.05) during the third and fourth 8-min cycles, and
nonresistive mechanisms were reduced by ECA from cycles 3-10 (P < 0.05). Then, at
the end of the infusion, the control and ECA dynamic values were similar (P <
0.05), although IOP of ECA-treated rats was still slightly reduced (P < 0.05).
The most likely explanation is a summation of small changes in both resistive and
nonresistive components of IOP dynamics. Systemic blood pressure was unchanged
within either group. The well-known effects of ECA on the trabecular meshwork,
alone, are insufficient to explain the dynamic changes in IOP observed in this
model.
PMID- 10193446
TI - Antianalgesic action of dynorphin A mediated by spinal cholecystokinin.
AB - Previous work indicates that the antianalgesic action of pentobarbital and
neurotensin administered intracerebroventricularly in mice arises from activation
of a descending system to release cholecystokinin (CCK) in the spinal cord where
CCK is known to antagonize morphine analgesia. Spinal dynorphin, like CCK, has an
antianalgesic action against intrathecally administered morphine. This dynorphin
action is indirect; even though it is initiated in the spinal cord, it requires
the involvement of an ascending pathway to the brain and a descending pathway to
the spinal cord where an antianalgesic mediator works. The aim of the present
investigation was to determine if the antianalgesic action of intrathecal
dynorphin A involved spinal CCK. All drugs were administered intrathecally to
mice in the tail flick test. Morphine analgesia was inhibited by dynorphin as
shown by a rightward shift of the morphine dose-response curve. The effect of
dynorphin was eliminated by administration of the CCK receptor antagonists
lorglumide and PD135 158. One hour pretreatment with CCK antiserum also
eliminated the action of dynorphin. On the other hand, the antianalgesic action
of CCK was not affected by dynorphin antiserum. Thus, CCK did not release
dynorphin. Both CCK and dynorphin were antianalgesic against DSLET but not DPDPE,
delta 2 and delta 1 opioid receptor peptide agonists, respectively. The results
suggest that the antianalgesic action of dynorphin occurred through an indirect
mechanism ultimately dependent on the action of spinal CCK.
PMID- 10193448
TI - Screening for prostate cancer.
PMID- 10193449
TI - Are we winning the battle against the human immunodeficiency virus.
PMID- 10193450
TI - Disability 1986 and beyond: 11 years on.
AB - Rehabilitation medicine is the fastest growing specialty in the UK. It is timely
to take stock of the present structure and assess what needs to be done to ensure
its appropriate development in the future.
PMID- 10193452
TI - How to do it in surgery: transanal endoscopic microsurgery.
AB - Transanal endoscopic microsurgery has been performed in our institution since
1993 (Curran et al, 1994). It involves the use of a specially designed operating
sigmoidoscope to excise benign and early invasive tumours from the rectum. It
allows for accurate dissection of these lesions ensuring safe and complete
excision with histological confirmation of this.
PMID- 10193451
TI - Carvedilol for heart failure: more than just a beta-blocker?
AB - Carvedilol is a non-selective beta-blocker, and the only one, in recent clinical
trials, to have shown a clear reduction in mortality. It is suggested that,
compared with other beta-blockers, carvedilol has additional advantageous effects
in heart failure, and should be considered as part of the routine treatment of
heart failure.
PMID- 10193453
TI - Early pregnancy assessment units.
PMID- 10193454
TI - Recurrent early pregnancy loss and genetic-related disturbances in folate and
homocysteine metabolism.
PMID- 10193455
TI - Oligomenorrhoea, polycystic ovary syndrome and recurring miscarriage.
PMID- 10193456
TI - Investigation of the immune system in recurrent infection.
AB - Individuals with increased susceptibility to infection may have an acquired or
inherited abnormality of the immune system. The complexities of human immunity
are such that to investigate the cause may appear a daunting prospect. However,
in this review we aim to outline the basic components of the immune system and to
provide a logical and stepwise approach to the investigation of immunodeficient
individuals.
PMID- 10193457
TI - Erythrocyte sedimentation rate, plasma viscosity and C-reactive protein in
clinical practice.
AB - Erythrocyte sedimentation rate, plasma viscosity and C-reactive protein have been
increasingly used as inflammatory indicators in assisting disease management. An
understanding of the characteristics and limitations of each indicator is
important.
PMID- 10193458
TI - Pitfalls in radiological diagnosis of lower limb injuries.
AB - Correct evaluation of trauma requires the radiological examination to be tailored
to the clinical assessment which determines not only the area imaged and
projections obtained, but on occasion further imaging even in the absence of
plain film abnormality. We illustrate these principles in the lower limb, and
area where accurate diagnosis can be both difficult and important.
PMID- 10193459
TI - Airway control in severe facial injury.
PMID- 10193460
TI - Ethics of abortion: in the public's view.
PMID- 10193461
TI - Controversies in palliative medicine.
PMID- 10193464
TI - Controversies in palliative medicine.
PMID- 10193465
TI - The autopsy in the 1990s.
PMID- 10193466
TI - Malaria prophylaxis for the 1990s and beyond.
PMID- 10193467
TI - Health economics: a beginner's guide.
AB - In a completely private health-care system we would rely on the market to ensure
that money on health care was well spent. In state systems we have to use
something else--health economics.
PMID- 10193468
TI - Changing tactics in the abortion argument: does a fetus feel pain?
PMID- 10193469
TI - Carpal tunnel decompression: open vs endoscopic.
AB - Carpal tunnel decompression is a common operation. While most patients report
satisfaction there are recognized complications. New endoscopic techniques are
claimed to reduce the incidence of these. However, the new techniques are not
without complications of their own.
PMID- 10193470
TI - Asthma: the role of fluticasone propionate.
AB - This report reviews the evidence for the role of fluticasone propionate in the
management of asthma, based on efficacy and safety trial data in over 4000 adults
and more than 1600 children suffering from asthma of varying severity. Overall,
fluticasone propionate at half the daily dose is at least as effective as
budesonide and as effective as beclomethasone dipropionate across a range of
doses.
PMID- 10193471
TI - Immunodeficiency syndromes and recurrent infection.
AB - Individuals with increased susceptibility to infection may have an acquired or
inherited abnormality of the immune system. In the second of two reviews we aim
to outline some of the most important immunodeficiency syndromes that may be
associated with a clinical presentation of frequent infection. Awareness of such
syndromes may aid pattern recognition and the appropriate investigation of
patients with recurrent infection.
PMID- 10193472
TI - Medical resources on the Internet.
PMID- 10193473
TI - Learning on the Internet.
PMID- 10193474
TI - So you want to be a trauma and orthopaedic surgeon.
PMID- 10193475
TI - So you want to train in urology.
PMID- 10193476
TI - So you want to train in paediatrics.
PMID- 10193477
TI - The management of ovarian cancer.
PMID- 10193478
TI - How to do it in surgery: laparoscopic rectopexy.
AB - Laparoscopically performed rectopexy is now possible, with all the advantages of
a minimally invasive technique. It may involve implantation of mesh (Cuesta et
al, 1993), suturing (Graf et al, 1995) of the reduced rectum or resection of
redundant colon (Baker et al, 1995). Essentially the laparoscopic operation
mimics the open procedure.
PMID- 10193479
TI - Liposarcoma: a review of current diagnosis and management.
AB - Liposarcoma is an uncommon sarcoma. Its presentation can be deceptive, varying
from innocuous to frank malignancy. Liposarcoma behaves differently from other
sarcomas. This article highlights the key prognostic factors of liposarcoma,
based on current literature, and suggests a plan of management.
PMID- 10193480
TI - Cost-effective monotherapy of concomitant benign prostatic hyperplasia and
hypertension.
AB - Increasing longevity in the developed world means an increasing prevalence of age
related disorders such as hypertension and benign prostatic hyperplasia (BPH). In
the case of BPH there are additional factors contributing to the increasing
number of patients requiring treatment. This review illustrates the potential
economic and effectiveness benefits of using one drug to treat two disorders.
PMID- 10193481
TI - Screening for breast cancer.
PMID- 10193482
TI - The autopsy in the 1990s.
PMID- 10193483
TI - A fiber matrix model for interstitial fluid flow and permeability in ligaments
and tendons.
AB - Collagen fibrils in ligaments and tendons are highly organized into parallel
arrays which influence interstitial fluid transport. Finite element (FE) models
were developed analogous to the fibrillar arrays in ligaments and tendons to
investigate interstitial fluid flow and tissue permeability as a function of
interfibrillar spacing and fluid properties. Collagen fibrils were assumed to be
a periodic square array of impermeable cylinders. A two-dimensional FE model was
used to study transverse fluid flow and a three-dimensional model was used to
study flow parallel to the collagen fibrils. Parametric FE analysis provided data
to formulate empirical expressions for permeability (kappa) as a function of
porosity (phi). Results show that longitudinal permeability (kappa = 1.1.10(
15)phi 2.5[1 - phi]-0.333) can be up to 50 times higher than transverse
permeability (kappa = 1.2.10(-15)phi 0.5[phi - phi min]2.5) in a compact array.
Maximum fluid shear stresses occur at the narrowest zones of adjacent fibrils
(1.21 Pa or 12.1 dyn/cm2 at 10 microns/s of average transverse influx). If
interstitial fluid is highly non-Newtonian, the permeability should be considered
as flow (shear)-dependent. The computational results suggest that tissue
permeability in ligaments and tendons is highly anisotropic, porosity-dependent,
and can be estimated by analytic expressions.
PMID- 10193484
TI - The filterability of leukocytes in undiluted blood.
AB - A filtrometer is described for measuring the flow of fluids through microfilters.
The flow of Newtonian fluids through the filters can be predicted from the
diameter, length and number of pores. There are no physical artefacts such as
turbulent flow or a significant lag period before steady-state flow is achieved.
The instrument has been used as a viscometer and has been used to record and
analyse the flow of undiluted blood through 5 microns polycarbonate filters. The
calculated viscosity of Newtonian fluids agrees well with those measured by a
more conventional viscometer (Ostwald). Flow profiles of blood have been analysed
to give both the numbers and the flow properties of a small population of slow
leukocytes which equate numerically with the monocytes. They are subdivided into
three distinct sub-populations, according to their rheological properties, and
these are termed SL1, SL2 and PB. The concentration of these cells, in blood, are
0.12 +/- 0.02 x 10(6) ml-1, 0.11 +/- 0.02 x 10(6) ml-1, 0.09 +/- 0.02 x 10(6) ml
1 in young females aged about 25 years. The transit time of these cells, through
5 microns pores, is 34.8 +/- 1.4 s, 147.5 +/- 2.5 s and > 300 s, respectively.
Analysis of blood from older men (53-79 years) gives essentially the same results
although the concentration of SL1 is slightly higher at 0.19 +/- 0.09 x 10(6) ml
1.
PMID- 10193485
TI - Use of polyester leukocyte elimination filters in blood filterability research.
AB - We tested a new routine to eliminate leukocytes for blood rheology measurements
using commercial leukocyte absorbing filters (here PALL RC400). These filters
were punched out and fitted in smaller chambers through which blood was filtered
under controlled suction pressure (< 30 mm Hg). This technique resulted in a very
effective leukocyte elimination to 0.0022% but also a platelet reduction to 0.2%.
The process causes a small but significant hemolysis with free hemoglobin, of the
order of 0.06% of the filtered erythrocytes. A small fraction of the erythrocytes
were retained in the filter, versus plasma, to reduce the hematocrit on the order
of 1.4%. The leukocyte filtration did not cause any detectable functional trauma
to the erythrocytes, measured as micro-pore filterability of normal and
glutaraldehyde (GA) hardened erythrocytes. However, when 10% of the erythrocytes
were hardened with GA, which caused an increase in pore clogging slope (p <
0.05), the additional passage through the leukocyte elimination filter removed
this measured change in clogging. This observation suggests that the leukocyte
elimination filter may selectively remove, not only leukocytes and platelets, but
also hardened erythrocytes. Reticulocyte counting did not reveal any selective
removal of young erythrocytes. In general, we find the presented method
reproducible, efficient and easy for eliminating leukocytes for blood rheology
research although the risk of removing undeformable erythrocytes must be
considered.
PMID- 10193486
TI - Determination of the content of nonfilterable cells in erythrocyte suspensions as
a function of the medium osmolality.
AB - The results of most filtration assays for deformability of erythrocytes do not
distinguish whether the entire population or only its small fraction exhibits
abnormal rheological properties. We developed a simple filtration method for
determination of the percentage of nonfilterable cells in erythrocyte suspension
using membrane filters with mean pore diameter of 3.1 microns. This method makes
it possible to detect even minor abnormal subpopulations in erythrocyte
suspensions. The flow rate of buffer depends on the number of free pores of a
filter. The plot of the number of pores clogged by nonfilterable cells vs the
total number of erythrocytes that were allowed to pass through the filter had a
linear portion, with a slope representing the relative content, Z%, of
nonfilterable cells in the suspension. We determined Z% for various medium
osmolalities u and used the data to derive the distribution of erythrocytes in
ucr (ucr is the maximum value of u at which an erythrocyte cannot pass through a
pore of a given filter because of geometric limitations). The distribution of ucr
in suspension of normal erythrocytes has a maximum of about 200 mOsm/kg and a
half-width of about 20 mOsm/kg. The distributions of ucr are altered in normal
erythrocyte suspensions at decreased pH values, in cryopreserved and ATP-depleted
erythrocyte suspensions and in erythrocytes from a xerocytosis patient.
PMID- 10193488
TI - The orthopod e-mail list.
PMID- 10193487
TI - Electrostatic repulsion among erythrocytes in tube flow, demonstrated by the
thickness of marginal cell-free layer.
AB - Electrostatic repulsion among erythrocytes in flow was evaluated through
measurement of the thickness of the marginal cell-free layer in narrow glass
tubes of 20-50 microns in inner diameter. To reduce the electrostatic repulsive
force, due mainly to sialic acid of the membrane glycoproteins, human
erythrocytes were treated with neuraminidase. The surface negative charge of the
erythrocytes, as determined from the electrophoretic mobility using free-flow
electrophoresis, was found to be proportional to the sialic acid content. When
erythrocytes with decreased sialic acid content flowed through narrow tubes, the
thickness of cell-free layer determined using an image processor increased even
in the absence of erythrocyte aggregation in the suspension. The effect was more
pronounced at acidic pH. The addition of Dextran T-70 (70,400 Mol. Wt.) further
increased the cell-free layer thickness due to erythrocyte aggregation. Thus,
reducing the negative charge density on the erythrocyte surface by itself
accelerates the axial accumulation of erythrocytes in flow due to the decreased
electrostatic repulsive force between the cells, even in the absence of
erythrocyte aggregation.
PMID- 10193489
TI - 'Clearance' of cervical spine injury in the obtunded patient.
AB - The need to exclude cervical spine injury ('clearance') in an obtunded patient
poses a dilemma. The purpose of this study was to find out the current practices
for tackling this situation around the country. A questionnaire was sent to all
Intensive Care Units who accept injured patients. There is a great diversity in
the management and investigation of these patients. There is clearly a need for a
recognised protocol for dealing with this difficult situation. Such a protocol is
suggested.
PMID- 10193490
TI - The effect of ongoing litigation on outcome scores following open reduction and
internal fixation of the calcaneum.
AB - All sixteen patients who had undergone open reduction and internal fixation
(ORIF) of the calcaneum by the senior author between April 1993 and August 1996
were included in the study. Two had died from unrelated illnesses and one had
failed to attend any follow-up following discharge. The remaining 13 were
reviewed by the main author. As part of a complete clinical, radiological and
functional assessment, Buckley and Meek (B&M) and Kerr and Atkins (K&A) outcome
scores were calculated as well as a satisfaction score obtained by a visual
analogue scale (VAS). Statistical analysis of the results using Wilcoxen's paired
and unpaired ranking scores showed that the initial grade of the fracture, degree
of operative reduction, correction of width of the heel and post-operative ranges
of motion had no significant correlation to either B&M or K&A outcome scores or
to the VAS score. However, the presence of ongoing litigation was significantly
correlated to the scores (VAS < 0.01, B&M < 0.05, K&A < 0.05). These findings
cast doubt on the validity of post operative scoring for fracture of the
calcaneum in the presence of ongoing litigation.
PMID- 10193491
TI - Spinal cord injuries in adolescents after gunshot wounds: an increasing
phenomenon in urban North America.
AB - While much attention is focused on firearm fatalities, the purpose of this study
was to determine the expense of acute medical care and the rehabilitation
experience of surviving adolescent patients in the USA with spinal cord injury
secondary to gunshot wounds. We analyzed a cohort of 19 patients, 18 of whom
survived 12 months after spinal cord injury. The need for primary medical care
related to the injury, current work and scholastic status, and satisfaction with
the quality of rehabilitation were determined. Ten were not involved in any type
of academic or meaningful activity, five had returned to school, three were
undergoing rehabilitation, and one patient died. Major complications were present
in 14 of the 18 patients. Thus, despite a high survival rate after spinal cord
injury in this USA population, considerable long-term disability persists, and
survivors report a low level of satisfaction with life.
PMID- 10193492
TI - Complement activation in injured patients occurs immediately and is dependent on
the severity of the trauma.
AB - In order to study the factors related to complement activation, the complement
activation products C3bc and TCC were measured in plasma at admittance and during
the stay in the intensive care unit in 108 consecutive patients with multiple
injuries. These patients were admitted to the surgical department during a 4
month period. Complement activation occurred immediately after the trauma and
correlated strongly with the Injury Severity Score and was inversely correlated
to the Base Excess. Complement activation also correlated with the number of
transfusions. Sepsis caused complement activation later during the stay in
hospital. All seven patients developing the adult respiratory distress syndrome
(ARDS) had increased complement activation, either on admission or later during
the stay in the intensive care unit. Complement activation is known to contribute
to organ damage following ischemia and reperfusion. Clinical studies have
demonstrated the importance of early restoration of adequate circulation and the
present demonstration of a strong negative correlation between complement
activation and Base Excess indicates that early restoration of aerobic metabolism
may reduce complement activation and the risk for organ dysfunction.
PMID- 10193493
TI - Imaging the problem scaphoid.
AB - Scaphoid fractures can be difficult to diagnose on X-ray, even at 2 weeks. We
have compared prospectively bone scanning versus MRI scanning in 22 patients with
persistent signs and symptoms suggestive of a scaphoid fracture at 2 weeks and
found both methods to be sensitive, but MRI to be more specific, particularly in
diagnosing soft tissue injuries like scapho-lunate ligament ruptures and
triangular fibrocartilage tears. An early MRI scan at 2 weeks allows the
clinician to make the appropriate decision in this group of patients whose
diagnoses include; occult scaphoid fractures, other occult carpal and radial
fractures, ligamentous injuries and those without apparent injuries. MRI has also
been useful in defining the group of injuries which may imitate a clinically
occult scaphoid fracture.
PMID- 10193494
TI - Is Pauwels classification still valid?
AB - Intracapsular proximal femoral fracture may be classified using the Pauwels
classification, which relates to the shearing angle of the fracture surface. It
implies that the greater the Pauwels angle, the higher will be the non-union
rate. The Pauwels angle was studied in a series of 335 patients and related to
the eventual radiological outcome. It was found that neither the Pauwels angle
nor the classification had any predictive value for the incidence of non-union. A
literature review of previous studies of the Pauwels angle indicated similar
results. The continued use of the Pauwels classification in determining if the
femoral head should be preserved or replaced is unsound.
PMID- 10193495
TI - Primary replacement of the humeral head in iatrogenically displaced fracture
dislocations of the shoulder: a report about six cases.
AB - Dislocation of the shoulder is a common injury and may be associated with a
variety of complications. We report six cases of primary replacement of the
humeral head where closed reduction of a shoulder dislocation associated with an
undisplaced fracture of the humeral neck led to displacement of the neck
fracture. All dislocations examined were anterior with a displaced greater
tubercle fracture. The patients had undergone closed reduction at other medical
centres and were referred to us because of iatrogenically displaced fracture
dislocations of the shoulder. Three were women and three were men with a mean age
of 52.8 years (range 38-72). Primary replacement of the humeral head was done in
an average of 9.3 days (range 2-30 days) following the injury. The average follow
up period was 30.2 months (range 12-55 months). Postoperative pain, active range
of motion and function were evaluated with the American Shoulder and Elbow
Surgeons Criteria. The forward flexion averaged 124 degrees, active external
rotation averaged 29 degrees and internal rotation (achieved movement) to the
second lumbar vertebra. Because of the high risk of avascular necrosis and severe
collapse of the humeral head, we conclude that the primary replacement of the
humeral head is the superior treatment option in iatrogenically displaced
fracture dislocations of the shoulder.
PMID- 10193496
TI - The epidemiology of open long bone fractures.
AB - Open long bone fractures occur with a frequency of 11.5 per 100,000 persons per
year. They are more common in males and they have a bimodal age distribution.
Open fractures of the tibial diaphysis are the commonest, but open femoral
diaphyseal, distal femoral and proximal tibial fractures tend to occur in the
most seriously injured patients. Lower limb open fractures are more severe than
open fractures of the upper limbs. Not only is the soft tissue damage less in
open upper limb fractures, but there are fewer associated musculoskeletal
injuries.
PMID- 10193497
TI - Distraction osteogenesis through high energy fractures.
AB - We present a series of three patients with segmental, high energy open tibial
fractures with bone loss (2-7 cm), where we have used distraction through a
fracture site to replace lost bone. The open fracture was treated by debridement
and shortening to eliminate the bone and soft tissue defect. Limb length was
restored by distraction instituted through the closed segmental fracture. The
length of regenerate formed at the fracture site ranged from 10 to 30 mm. In each
case, bone formation at the distracted fracture site was satisfactory and times
for regenerate consolidation were similar to those seen in standard
corticotomies. These findings suggest that new bone will form in distraction
reliably from high-energy fracture sites.
PMID- 10193498
TI - A simple laser guide to reduce the screening time during the insertion of dynamic
hip screws.
AB - A simple laser pointer can be used to guide the radiographer to position the
image intensifier during the insertion of a dynamic hip screw in the treatment of
fractures of the trochanteric area of the proximal femur. This significantly
reduces the screening time and, by implication, the amount of radiation for the
theatre staff and patient.
PMID- 10193499
TI - Crepitus following a dog bite.
PMID- 10193500
TI - Chronic posterior knee dislocation: treatment with arthrolysis, posterior
cruciate ligament reconstruction and hinged external fixation device.
PMID- 10193501
TI - A method of treatment of non-union of humeral shaft fractures following treatment
by locked intramedullary nail: a report of three cases.
PMID- 10193502
TI - Complex floating knee; trifocal tibial and ipsilateral femoral fracture.
PMID- 10193503
TI - Tension pneumothorax in the presence of bilateral intercostal chest drains.
PMID- 10193504
TI - Remodelling of valgus deformity secondary to proximal metaphyseal fracture of the
tibia.
PMID- 10193505
TI - Incarcerated lumbar hernia--delayed consequence of a seat belt injury.
PMID- 10193506
TI - Finger flaps: using the modified neurovascular Tranquilli-Leali flap.
PMID- 10193507
TI - Spontaneous reduction of an inferior acromioclavicular joint dislocation.
PMID- 10193508
TI - Failure of femoral head fixation: a cadaveric analysis of lag screw cut-out with
the gamma locking nail and the AO dynamic hip screw.
PMID- 10193510
TI - Cell cycle regulators and their abnormalities in breast cancer.
AB - One of the main properties of cancer cells is their increased and deregulated
proliferative activity. It is now well known that abnormalities in many positive
and negative modulators of the cell cycle are frequent in many cancer types,
including breast carcinomas. Abnormalities such as defective function of the
retinoblastoma gene and cyclin-dependent kinase inhibitors (for example, p16,
p21, and p27), as well as upregulation of cyclins, are often seen in breast
tumours. These abnormalities are sometimes coincidental, and newly described
interplays between them suggest the existence of a complex regulatory web in the
cell cycle.
PMID- 10193511
TI - Demystified ... cell cycle.
PMID- 10193509
TI - Genetic risk factors in Alzheimer's disease.
AB - Following a brief introduction and discussion of the pathological features of
Alzheimer's disease, the main emphasis of this review article will be the genetic
factors that have been implicated in this disease. These can be divided into two
main categories. First, the three genes in which mutations are known to result in
early onset autosomal dominant familial Alzheimer's disease will be discussed.
These are well characterised but account for only a small proportion of
Alzheimer's disease cases. Late onset, sporadic Alzheimer's disease is more
common and evidence suggests that there is a genetic component to this type of
disease. A number of genetic risk factors have been implicated that might
increase the risk of developing sporadic disease. Many of these are controversial
and studies have shown conflicting results, which are discussed in this section.
Finally, a brief discussion of some of the mechanisms suggested to play a role in
the pathogenesis of Alzheimer's disease is included. It is hoped that this will
show why particular genes have been implicated in Alzheimer's disease and how
they might be able to influence the development of the disease.
PMID- 10193512
TI - Intracellular accumulation of the amyloidogenic L68Q variant of human cystatin C
in NIH/3T3 cells.
AB - AIM: To study the cellular transport of L68Q cystatin C, the cystatin variant
causing amyloidosis and brain haemorrhage in patients suffering from hereditary
cystatin C amyloid angiopathy (HCCAA). METHODS: Expression vectors for wild-type
and L68Q cystatin C were constructed and used to transfect mouse NIH/3T3 cells.
Stable cell clones were isolated after cotransfection with pSV2neo. Clones
expressing human wild-type and L68Q cystatin C were compared with respect to
secreted cystatin C by enzyme linked immunosorbent assay (ELISA), and for
intracellular cystatin C by western blotting and immunofluorescence
cytochemistry. Colocalisation studies in cells were performed by double staining
with antibodies against human cystatin C and marker proteins for lysosomes, the
Golgi apparatus, or the endoplasmic reticulum, and evaluated by confocal
microscopy. RESULTS: Concentrations of human cystatin C secreted from transfected
NIH/3T3 cells were similar to those secreted from human cells in culture. In
general, clones expressing the gene encoding L68Q cystatin C secreted slightly
lower amounts of the protein than clones expressing wild-type human cystatin C.
Both immunofluorescence cytochemistry and western blotting experiments showed an
increased accumulation of cystatin C in cells expressing the gene encoding L68Q
cystatin C compared with cells expressing the gene for the wild-type protein. The
intracellularly accumulating L68Q cystatin C was insoluble and located mainly in
the endoplasmic reticulum. CONCLUSIONS: The cellular transport of human cystatin
C is impeded by the pathogenic amino acid substitution Leu68-->Gln. The resulting
intracellular accumulation and increased localised concentration of L68Q cystatin
C might be an important event in the molecular pathophysiology of amyloid
formation and brain haemorrhage in patients with HCCAA.
PMID- 10193513
TI - Ki-67: a useful marker for the evaluation of dysplasia in ulcerative colitis.
AB - AIMS: Evaluation of dysplasia in long standing ulcerative colitis is a difficult
and often subjective task. Therefore, the aim of this study was to search for a
more objective parameter to help distinguish regenerative changes from epithelial
dysplasia. METHODS: A total of 97 sections from colectomy specimens from 12
patients with ulcerative colitis of more than 10 years duration were stained
immunohistochemically with MIB 1 to detect differences in the frequency and
pattern of nuclei positive for the proliferation marker Ki-67. All patients had
epithelial dysplasia in one or more areas (high grade dysplasia, n = 16; low
grade dysplasia, n = 15; indefinite for dysplasia, n = 16), and three patients
had additional adenocarcinoma (one Dukes's C multifocal, mucinous carcinoma; one
Dukes's C adenocarcinoma in the sigmoid; and one Dukes's A adenocarcinoma in the
caecum). Two patients had adenomas--one had an 8 cm villous adenoma with
intramucosal carcinoma, and the other had a 4 cm tubulovillous adenoma with high
grade dysplasia. RESULTS: There were highly significant differences between the
percentages of Ki-67 immunopositive cells in low grade and high grade dysplasia
and carcinoma compared with regenerative epithelium. In high grade dysplasia and
carcinoma, the distribution of Ki-67 positive cells was diffuse throughout the
full length of the crypt, whereas low grade dysplasia and epithelium indefinite
for dysplasia, as well as regenerative epithelium, showed an expanded basal zone.
CONCLUSIONS: Assessment of the number of Ki-67 immunostained cells is of
additional value in deciding whether the mucosa is regenerative or dysplastic,
and the MIB 1 staining pattern is characteristic for most lesions with high grade
dysplasia and carcinoma. Therefore, this technique could be combined with routine
histological evaluation of colorectal epithelium being examined for dysplasia.
PMID- 10193514
TI - Detection of t(14;18) carrying cells in bone marrow and peripheral blood from
patients affected by non-lymphoid diseases.
AB - AIMS/BACKGROUND: To assess the presence of bcl-2/JH rearrangements in bone marrow
and peripheral blood lymphocytes from patients affected by diseases other than
malignant lymphomas. The t(14;18) (q32;q21) translocation, which juxtaposes the
bcl-2 oncogene on chromosome 18 and the JH segment of the immunoglobulin heavy
chain (IgH) genes on chromosome 14, is found frequently in follicular lymphomas.
METHODS: A sensitive semi-nested polymerase chain reaction (PCR) was used to
detect t(14;18) translocation in bone marrow aspirates and peripheral blood
lymphocytes from 48 patients. In 137 additional individuals peripheral blood
lymphocytes only were tested. RESULTS: Cells carrying bcl-2/JH rearrangements
were detected in about a quarter of the bone marrow samples and half of the
peripheral blood lymphocyte samples. In seven patients, t(14;18) positive cells
were found in both the bone marrow and peripheral blood lymphocyte samples. The
size of the PCR products and bcl-2/JH DNA sequence analysis showed that the same
t(14;18) carrying clone was present in the bone marrow and the corresponding
peripheral blood lymphocyte samples in three of these seven patients. Some
patients had more than one bcl-2/JH rearrangement. There was no significant
correlation between age and the translocation incidence. Cells carrying the
t(14;18) translocation were present in peripheral blood lymphocyte samples with a
similar incidence--between 47% and 52% in all age groups from 20 to 79 years.
Patients older than 80 years had a lower (37%) but not significantly different
incidence. CONCLUSIONS: These findings suggest that patients affected by non
lymphoid diseases may have several t(14;18) carrying cells and some of them
undergo a clonal expansion. Whether individuals with t(14;18) positive cells are
at a higher risk of lymphoid malignancies remains unanswered and further
epidemiological studies are required.
PMID- 10193515
TI - Identification of a novel PTEN mutation (L139X) in a patient with Cowden disease
and Sjogren's syndrome.
AB - Cowden disease is an autosomal dominant disorder associated with an increased
risk of breast, thyroid, and skin cancer in which germline mutations in a
candidate tumour suppressor gene (PTEN) have been identified previously.
Sjogren's syndrome is a chronic inflammatory and autoimmune disorder of exocrine
glands for which the genetic basis is unknown. This report describes a novel PTEN
mutation (L139X) in a patient with Cowden disease and Sjogren's syndrome. This
observation raises the possibility of a link between mutations in the PTEN gene
and Sjogren's syndrome.
PMID- 10193516
TI - Gel staining methods for detection of telomerase activity with the telomeric
repeat amplification protocol (TRAP) assay.
PMID- 10193517
TI - BRCA1 and BRCA2 proteins: roles in health and disease.
AB - Between 5% and 10% of all breast cancer is hereditary, with patients having a
strong family history of the disease. The remaining 90-95% of cases are classed
as sporadic. Within the inherited group, 80-90% of cases are the result of
germline mutations affecting two recently identified genes: BRCA1 and BRCA2.
Since the sequencing of these genes, considerable research on the genetics of the
mutation carriers has been performed, with less attention having been focused on
the BRCA1 and BRCA2 proteins themselves. The structure and function of the
protein products thus continues to hold mystery and might be the key to the full
understanding of this complex disease.
PMID- 10193518
TI - Demystified ... p53.
PMID- 10193519
TI - Apoptosis and expression of Bax, Bcl-x, and Bcl-2 apoptotic regulatory proteins
in colorectal carcinomas, and association with p53 genotype/phenotype.
AB - AIMS: Spontaneous apoptosis and expression of the apoptotic regulatory proteins
Bax, Bcl-x, and Bcl-2 were investigated in 50 colorectal carcinomas. The p53
genotypes/phenotypes and BAX genotypes were also determined, and possible
associations of these with apoptosis and/or with expression of the different
apoptotic regulatory proteins were studied. METHODS: Terminal deoxynucleotidyl
transferase (TdT) mediated dUTP labelling of DNA fragments was used to detect
apoptotic tumour cells in sections and peroxidase immunohistochemistry was used
to assess protein expression. p53 genotype/phenotype was determined using
constant denaturant gel electrophoresis/immunoblotting and bax genotype was
determined using polymerase chain reaction based methods. RESULTS: The
distribution of tumour apoptotic indices was bimodal with a natural cut off at
1.0% (range, 0.0-5.4%); the median fraction of apoptotic tumour cells was 0.8%.
Tumour apoptosis was not associated significantly with tumour DNA ploidy status.
Normal mucosal tissue had less than 0.1% apoptotic cells. Staining intensities
for Bax, Bcl-x, and Bcl-2 were strong; that is, equivalent to or greater than
positive normal mucosal cells, in 11 of 50, 20 of 49, and 20 of 48 carcinomas.
Frameshift mutations in the bax gene were detected in three of 42 tumours
analysed, all of which were DNA diploid, and Bax protein expression in these
tumours was absent or very low. Bax, Bcl-x, and Bcl-2 protein expression were not
correlated with tumour apoptosis or tumour DNA ploidy status. p53 was expressed
in 34 of 50 tumours and p53 gene mutations were detected in 22 of 29 p53 positive
tumours analysed. Apoptosis was significantly lower in a greater number of p53
positive tumours than p53 negative tumours. In addition, Bcl-2 protein expression
was significantly higher in a greater number of p53 positive tumours compared
with p53 negative tumours. Bax and Bcl-x protein expression were not
significantly associated with p53 phenotype/genotype. CONCLUSIONS: The results
indicate that acquisition of a p53 phenotype is associated with lower spontaneous
apoptosis and higher expression of Bcl-2. The results also suggest that p53 is
not a major determinant for Bax expression in colorectal carcinomas in vivo.
PMID- 10193520
TI - Analysis of the frequency of microsatellite instability and p53 gene mutation in
splenic marginal zone and MALT lymphomas.
AB - AIMS: Studies of the genetic characteristics of splenic marginal zone lymphoma
(SMZL) have failed to identify genetic changes specific to this tumour.
Microsatellite instability is a type of genomic instability associated with
different types of human cancer. Although microsatellite instability is rare in B
cell non-Hodgkin's lymphomas, it has been found in some specific subsets, such as
marginal zone lymphomas arising in mucosa associated lymphoid tissue (MALT),
where an association with p53 mutation has been described. Because it has been
proposed that SMZL and MALT are close in histogenetic terms, this study
investigated the comparative frequency of microsatellite instability and p53
mutation in patients with SMZL and MALT lymphomas. METHODS: Microsatellite
instability was investigated using seven microsatellite marker loci in 14
patients with SMZL and 20 patients with MALT lymphomas. In an attempt to clarify
the role of p53 gene mutation in the pathogenesis of SMZL, exons 5-8 were also
investigated by polymerase chain reaction single strand conformation polymorphism
(PCR-SSCP) and direct sequencing in a total of 20 patients with SMZL and 22
patients with MALT lymphomas. RESULTS: Microsatellite instability was not
detected in patients with SMZL, although five of 20 patients with MALT lymphomas
had microsatellite instability. The frequency of p53 mutation was low in both
series (two of 20 patients with SMZL and one of 22 patients with MALT lymphomas).
No significant association was found between p53 mutation and microsatellite
instability. CONCLUSIONS: These results indicate that microsatellite instability
is not associated with the molecular pathogenesis of SMZL, confirming the
relatively increased frequency of microsatellite instability in MALT lymphomas,
and perhaps suggesting that MALT and SMZL have different mechanisms of
tumorigenesis.
PMID- 10193521
TI - Nuclear DNA content and p53 overexpression in stage I squamous cell carcinoma of
the tongue compared with advanced tongue carcinomas.
AB - AIMS: To evaluate the predictive value of the nuclear DNA content (image
cytometry) and p53 overexpression (immuno-histochemistry using antibody CM-1) in
uniformly treated stage I carcinomas of the mobile tongue. Also, to compare stage
I carcinomas with advanced tongue carcinomas (stages II-IV). METHODS: Archival
formalin fixed, paraffin wax embedded tumour specimens from 54 patients with
stage I squamous cell carcinoma and 37 patients with advanced squamous cell
carcinoma were analysed. Mean follow up time of the stage I carcinomas was 71
months (median, 62.5; range, 6-175). RESULTS: Twenty three patients (stage I) had
recurring disease: 10 had local recurrence (in the tongue) and 13 had regional
recurrence (cervical metastases). Locally recurring stage I carcinomas had a more
pronounced DNA deviation than the other stage I carcinomas and this degree of
deviation was comparable with the DNA content of advanced carcinomas. Stage I
carcinomas that developed regional recurrences overexpressed p53 more frequently.
In Cox multivariate regression analysis of time to recurrence, DNA deviation was
a significant parameter in tumours that recurred locally (p = 0.032). p53
overexpression was the only parameter close to significance for regional
recurrence (p = 0.065). CONCLUSIONS: Nuclear DNA content and p53 immunostaining
are of value for the prediction of recurrence of stage I squamous cell carcinomas
of the mobile tongue. Stage I tongue carcinomas that are prone to local
recurrence show the same DNA content as do advanced tongue carcinomas.
PMID- 10193522
TI - The monocyte chemotactic protein a (MCP-1) and interleukin 8 (IL-8) in Hodgkin's
disease and in solid tumours.
AB - AIMS: Monocyte chemotactic protein 1 (MCP-1) and interleukin 8 (IL-8) are small,
inducible proteins with chemotactic activity for specific subsets of leucocytes.
The possibility that MCP-1 and IL-8 are produced in tissues involved by Hodgkin's
disease, thus contributing to the inflammatory-type background of the lesion, was
investigated. METHODS: The presence of RNA transcripts for MCP-1 and IL-8 was
investigated in biopsy samples of 24 cases of Hodgkin's disease, 17 non-Hodgkin's
malignant lymphomas, 30 solid tumours, and 30 histologically normal tissues by
means of reverse transcription-polymerase chain reaction (RT-PCR)/Southern blot
analysis. RESULTS: MCP-1 expression was detected in 23 of 24 cases of Hodgkin's
disease, in seven of 17 cases of B cell non-Hodgkin's lymphoma, and in seven of
14 cases of reactive lymphoid hyperplasia. IL-8 was present in six of 14 cases of
Hodgkin's disease, and was seen only rarely in B cell non-Hodgkin's lymphoma and
in reactive lymphoid tissues. MCP-1 and IL-8 RNA transcripts were detected in 13
of 25 carcinomas originating from the lung, breast, thyroid, and ovary.
CONCLUSIONS: These findings are consistent with the possibility that MCP-1 and IL
8 are two additional cytokines involved in the pathogenesis of Hodgkin's disease.
PMID- 10193523
TI - Molecular detection of acute lymphoblastic leukaemia in boys with testicular
relapse.
AB - AIMS: To determine the role of polymerase chain reaction (PCR) based minimal
residual disease (MRD) detection of leukaemia specific DNA in testicular relapse
in childhood acute lymphoblastic leukaemia. METHODS: DNA was obtained from
archival testicular and bone marrow samples from boys with acute lymphoblastic
leukaemia who relapsed in the testes. Overlapping DJH clone specific primers
derived from clonal immunoglobulin heavy chain (IgH) gene rearrangement in each
case were used to analyse testicular or bone marrow DNA. RESULTS: Histologically
normal end of treatment testicular biopsies in the five patients in longterm
remission were all MRD negative, but MRD positive in three of six boys with
subsequent testicular relapse. Histologically normal bone marrow samples taken at
the end of treatment were MRD negative in five of seven cases, but MRD positive
in all cases at the time of isolated testicular relapse. Three boys with
unilateral testicular relapse underwent unilateral orchidectomy, rather than
bilateral testicular irradiation, as part of their treatment. Two of these boys
were MRD positive in the histologically uninvolved testes, and both had
subsequent relapses either in the testes or the bone marrow, while the MRD
negative patient has not had a testicular relapse. CONCLUSIONS: The presence of
MRD in testicular tissue can be assayed with a PCR based method to detect clone
specific antigen receptor gene rearrangements. In this setting, PCR is more
sensitive than conventional testicular histology for predicting clinical
outcomes. MRD assays might be useful in the management of boys at the time of
isolated testicular relapse, to confirm the presence of unilateral testicular
disease.
PMID- 10193524
TI - Stromelysin 1, neutrophil collagenase, and collagenase 3 do not play major roles
in a model of chondrocyte mediated cartilage breakdown.
AB - AIMS: To determine the collective roles of stromelysin 1, neutrophil collagenase,
and collagenase 3 in chondrocyte mediated cartilage proteoglycan and type II
collagen degradation in tissue culture model systems. METHODS: Bovine nasal
cartilage explants were cultured with and without recombinant human interleukin 1
alpha (IL-1 alpha), recombinant human tumour necrosis factor alpha, or retinoic
acid. Proteoglycan and type II collagen release were determined by colorimetric
assay and immunoassay, respectively, in the absence and presence of matrixin
inhibitors. Potential toxic effects of the inhibitors were assessed by measuring
rates of glycolysis. RESULTS: Loss of proteoglycan and type II collagen from
nasal cartilage was inhibited by batimastat, a broad spectrum matrixin inhibitor.
BB-3437, a selective inhibitor of stromelysin, neutrophil collagenase, and
collagenase 3, at the concentrations used in this study, showed a weak but dose
dependent inhibitory effect on the IL-1 stimulated degradation of type II
collagen, but had virtually no effect on proteoglycan breakdown. Neither
inhibitor affected rates of glycolysis. CONCLUSIONS: Stromelysin 1, neutrophil
collagenase, and collagenase 3 are unlikely to contribute to chondrocyte mediated
proteoglycan degradation in our model system. The modest effect of a selective
inhibitor of these enzymes on IL-1 stimulated collagen breakdown suggests a minor
role for one or more of these proteinases; potent inhibition by an inhibitor of
interstitial collagenase and the gelatinases suggests that these enzymes play a
major role in IL-1 stimulated, chondrocyte mediated type II collagen breakdown
from nasal cartilage.
PMID- 10193525
TI - Detection of alterations in all three exons of the peripherin/RDS gene in Swedish
patients with retinitis pigmentosa using an efficient DGGE system.
AB - AIMS: To develop a sensitive mutation screening procedure suitable for routine
analysis of the peripherin/RDS gene, and to estimate the nature and prevalence of
peripherin/RDS gene mutations in Swedish patients with autosomal dominant
retinitis pigmentosa. METHODS: To make the method as sensitive as possible, as
many as eight segments, covering the three exons and the flanking intron
sequences of the peripherin/RDS gene, were analysed by denaturing gradient gel
electrophoresis. A group of 38 Swedish patients with a clinical diagnosis of
autosomal dominant retinitis pigmentosa were screened for mutations in the
peripherin/RDS gene. RESULTS: Three point mutations were found in four of the
patients and five polymorphisms were defined. One mutation in exon 1, R172W, has
been described previously in other ethnic groups as causing a macular
degeneration. Another mutation, in exon 2 and causing the substitution F211L, was
found in two unrelated patients. A third mutation, resulting in the likely non
pathogenic substitution S289L, as well as a polymorphism not reported previously,
was found in exon 3. CONCLUSIONS: The screening procedure described allows
detection of mutations in all of the exons, including the polymorphic 5' and 3'
ends of the gene, and is therefore suitable for routine screening of
peripherin/RDS gene defects in patients with autosomal dominant retinitis
pigmentosa. The frequency of mutations found in the Swedish patient group
indicates that defects in the peripherin/RDS gene might be a more common cause of
autosomal dominant retinitis pigmentosa than was thought previously.
PMID- 10193526
TI - Regulation of lecithin cholesterol acyltransferase activity.
PMID- 10193527
TI - The lipids of pulmonary surfactant: dynamics and interactions with proteins.
PMID- 10193528
TI - Inhaled corticosteroids are considered by many to be the most effective therapy.
PMID- 10193529
TI - Comparative physicochemical and pharmacokinetic profiles of inhaled
beclomethasone dipropionate and budesonide.
AB - The physicochemical and pharmacokinetic characteristics of BDP and budesonide are
somewhat different, but the overall result is that both are well suited for use
as inhaled corticosteroids. Both BDP and budesonide are metabolized primarily by
the liver, with one of the metabolites of BDP, 17-BMP, having greater receptor
affinity than either the parent compound or budesonide, which has no active
metabolites. BDP has a lower water solubility than either 17-BMP or budesonide,
which have similar water solubilities. Budesonide has lower oral bioavailability
than BDP; however, it is generally reported to have a longer plasma half-life
than either BDP or 17-BMP. The physicochemical and pharmacokinetic profiles of
inhaled BDP and budesonide provide both compounds with a favourable ratio of
topical to systemic effects and support their well-established role in the
treatment of asthma. The device used to deliver an inhaled corticosteroid
influences the lung deposition of the drug and selection of the device should be
made with an understanding of the particular advantages and disadvantages of the
device for each individual patient.
PMID- 10193530
TI - Efficacy of inhaled beclomethasone dipropionate and budesonide in the treatment
of asthma.
PMID- 10193531
TI - Effect of inhaled beclomethasone dipropionate and budesonide on adrenal function,
skin changes and cataract formation.
PMID- 10193532
TI - Comparative review of the effects of inhaled beclomethasone dipropionate and
budesonide on bone.
PMID- 10193533
TI - Effect of inhaled beclomethasone dipropionate and budesonide on growth in
children with asthma.
PMID- 10193534
TI - Is early enteral feeding of benefit?
PMID- 10193535
TI - Continuous cardiac output monitoring--further applications of the thermodilution
principle.
PMID- 10193536
TI - Antioxidant status in patients with acute respiratory distress syndrome.
PMID- 10193537
TI - Sedation, where are we now?
PMID- 10193538
TI - When to customize a severity model.
PMID- 10193539
TI - Severe community-acquired pneumococcal pneumonia -- what might be done better.
PMID- 10193540
TI - The management of severe acute necrotising pancreatitis: an evidence-based review
of the literature.
AB - Clearly the main determinant of outcome in severe acute pancreatitis is the
extent of pancreatic necrosis and the subsequent risk for the development of
infected necrosis. A thorough assessment using appropriate scoring systems and
the early use of dynamic contrast-enhanced CT will highlight those patients
likely to benefit from higher dependency or intensive care. Despite numerous
suggested specific therapies there is still no Grade A evidence that any confers
a significant mortality benefit. However, general supportive measures should
include vigorous replacement of fluid losses to correct the circulating volume,
correction of electrolyte and glucose abnormalities, and respiratory,
cardiovascular and renal support as necessary. Those patients with infected
pancreatic necrosis or deteriorating organ systems should undergo surgery.
Patients with sterile necrosis should receive a broad-spectrum prophylactic
antibiotic which adequately penetrates pancreatic tissue. Due attention should
also be paid to nutritional support, for which a jejunal feeding tube with EN is
recommended as early as is achievable.
PMID- 10193541
TI - Effects of early enteral nutrition on intestinal permeability and the development
of multiple organ failure after multiple injury.
AB - OBJECTIVE: To determine how immediate enteral nutrition (EN) affects gut
permeability and the development of multiple organ failure (MOF) in multiply
injured patients. DESIGN: Prospective, randomised clinical trial. SETTING: 20-bed
surgical intensive care unit (ICU), university hospital. PATIENTS: 28 consecutive
multiply injured patients, admitted in shock and stabilised in 6 h.
INTERVENTIONS: Patients were randomly assigned to EN started not later than 6 h
after admission to the ICU (group A), and to EN started later than 24 h after
admission (group B). MEASUREMENTS AND MAIN RESULTS: The lactulose/mannitol (L/M)
test was performed in patients on days 2 and 4 after trauma, and in 5 healthy
volunteers. MOF scores were calculated daily. The mean MOF score from day 4
onwards was 1.84 in group A versus 2.81 in group B (p < 0.002), and was
correlated with the time of initiation of EN after injury and the L/M ratio on
day 2. The median L/M ratio on day 2 was 0.029 for group A and 0.045 for group B,
while on day 4 it was 0.020 and 0.060, respectively. On day 2 after trauma, the
L/M ratio was significantly higher in group B (p < 0.05) than in normal
volunteers (median 0.014) and was positively correlated with the time of starting
EN. CONCLUSIONS: In contrast with normal volunteers, the patients started on EN
later than 24 h after admission to the ICU demonstrated increased intestinal
permeability on the second day after sustaining multiple injury. Also, they had a
more severe form of MOF than the group placed on EN immediately upon admission.
However, early EN had no influence on the length of ICU stay or the time of
mechanical ventilation.
PMID- 10193542
TI - Advantages of endoscopic therapy of gastrojejunal dissociation in critical care
patients.
AB - OBJECTIVE: To evaluate the advantages of a new three-lumen tube (Trelumina) and a
percutaneous endoscopic gastrostomy (EntriStar) with a jejunal insertion tube
(PEGJ) as a safe method of early enteral nutrition and simultaneous gastric
decompression as well as fast reduction of the high gastric reflux in critical
care patients. DESIGN: Retrospective, descriptive case series. SETTING: Two
anaesthesiological and one surgical intensive care unit (ICU) in a university
hospital. PATIENTS: Sixty-five consecutive critically ill patients with
gastrojejunal dissociation. The mean Acute Physiology and Chronic Health
Evaluation Score (APACHE II) was 19. INTERVENTIONS: Placement of 46 Trelumina and
19 PEGJ under endoscopic control. MEASUREMENTS AND MAIN RESULTS: None of the
known percutaneous endoscopic gastrostomy (PEG) complications like wound
infection, bleeding or organ perforation were seen. One secondary dislocation of
the jejunal insertion tube and four dislocations of the jejunal part of the
Trelumina were found. The average gastric reflux of the Trelumina and the PEGJ
amounted to 1700 +/- 230 ml/day. Forty-three patients showed a clear decrease in
the gastric reflux to 450 +/- 200 ml/day within the first 24 h of tube placement.
The average time of reduction to normal gastric reflux volumes (0-200 ml/day)
amounted to 4 -/+ 2 days. Forty-three (71 %) of the patients showed improved
intestinal passage as expressed by regular peristalsis and defaecation. The price
for 1 day enteral feeding via Trelumina or PEGJ was 10 times lower than 1 day
total parenteral nutrition. CONCLUSIONS: Placement of the Trelumina and the PEGJ
is a safe, successful and inexpensive means of early enteral nutrition and
simultaneous gastric reflux reduction in critical care patients.
PMID- 10193543
TI - Continuous thermodilution cardiac output: clinical validation against a reference
technique of known accuracy.
AB - OBJECTIVE: To evaluate the accuracy and precision of continuous thermodilution
(CCO) by using a validated bolus thermodilution (BCO) reference technique as
criterion standard. DESIGN: Under circulatory steady state conditions, a CCO
system (Vigilance, software versions 4.35 and 4.39) was validated with regard to
CCO as well as iced and room temperature BCO. SETTING: Intensive care unit at a
university hospital. PATIENTS: Method comparison was conducted in 56 cardiac
surgical patients, 28 patients being allocated to one of the two software
versions, and 14 within each group to either iced or room temperature BCO.
MEASUREMENTS AND RESULTS: CCO readings were registered in duplicate before and
after three to five bolus injections conducted with both the Vigilance and
reference systems. Iced BCO showed excellent agreement between the Vigilance and
reference systems, yielding SDs of bias of 0.41 and 0.37 l/min and linear
correlation coefficients (r) of 0.97 and 0.96. With room temperature BCO,
agreement was significantly less. CCO, irrespective of software version, showed
higher SDs of bias (0.90 and 0.84 l/min) and lower r values (0.84 and 0.81) than
iced BCO (p < 0.0001). CCO measurements with software version 4.39 yielded a
similar SD of bias to that with room temperature BCO. CONCLUSION: Decreased
precision of CCO as compared to iced BCO may, in clinical settings, be outweighed
by the advantages of automated and continuous monitoring. Under research
conditions, however, iced BCO remains the method of choice.
PMID- 10193544
TI - A new simple method to perform pressure-volume curves obtained under quasi-static
conditions during mechanical ventilation.
AB - OBJECTIVE: To describe a fast, simple method to acquire pressure-volume curves of
the respiratory system and to compare this with a classic method in terms of
reliability of the data and speed. DESIGN: Acquisition of pressure-volume curves
by low flow inflation technique (P-Vlf) versus the occlusion technique (P-Vst)
using the standard equipment of a Cesar ventilator. SETTING: General ICU - Aix en
Provence Hospital. PATIENTS: Ten sedated, curarized patients undergoing
mechanical ventilation. INTERVENTIONS: P-Vlf curves were acquired by setting the
ventilator parameters at f = 5 c./min, duty time Ti/Ttot = 80 %, VT = 1100 ml,
pause time = 0. The pressure and volume data were collected directly on the
ventilator screen. P-Vst curves were acquired using an airway occlusion
technique. The pressures obtained for the same inflation volumes and times
necessary for performance of the two techniques were compared. RESULTS: The time
needed to acquire a P-Vlf curve was 3 min versus 38 min for P-Vst curve.
Concordance analysis between the two methods showed a 95 % confidence interval of
(-0.5 cm H2O, + 1.8 cm H2O) for pressure. CONCLUSIONS: P-Vlf curves are close to
P-Vst curves, are much less time-consuming, easy to acquire with Cesar ventilator
equipment, and may be used in clinical routine to assess the elastic properties
of the respiratory system.
PMID- 10193545
TI - Antioxidant status in patients with acute respiratory distress syndrome.
AB - OBJECTIVES: Reactive oxygen species (ROS) have been implicated in the
pathophysiology of ARDS. We investigated the pattern of antioxidants in plasma
and ROS production by neutrophils in patients with ARDS over 6 days. DESIGN:
Observational study. Blood samples were taken when the diagnosis was made (D0)
and after 3 (D3) and 6 days (D6) during therapy. SETTING: Intensive care units at
a University Hospital. PATIENTS: Eight patients with ARDS were investigated, 17
healthy volunteers served as controls. MEASUREMENTS AND RESULTS: Plasma levels of
ascorbate, alpha-tocopherol, retinol, beta-carotene, selenium and lipid
peroxidation products (MDA) were determined and the activities of the
antioxidative enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione
peroxidase (GSH-PX) in erythrocytes were measured. In addition, ROS production
(superoxide anion and hydrogen peroxide) in activated neutrophils was assessed.
Plasma levels of alpha-tocopherol, ascorbate, beta-carotene and selenium were
reduced from the onset of illness. MDA plasma levels were increased throughout
the illness. ROS generation from neutrophils was normal on D0 and decreased to D6
in ARDS patients. CONCLUSION: The antioxidative system is severely compromised in
patients with ARDS. Plasma levels of alpha-tocopherol, ascorbate, beta-carotene
and selenium are decreased. Elevated MDA levels provide further evidence of
massive oxidative stress. The routine replacement of micronutrients according to
recommended daily allowances was inadequate to compensate for the increased
requirements.
PMID- 10193546
TI - Use of sedatives, analgesics and neuromuscular blocking agents in Danish ICUs
1996/97. A national survey.
AB - OBJECTIVE: To assess the use of sedatives, analgesics and neuromuscular blocking
agents (NMBAs) in patients requiring mechanical ventilation in Danish Intensive
Care Units (ICUs). DESIGN: Questionnaires were mailed in December 1996 to all
Departments of Anaesthesiology listed in the Annual Directory of Danish
Hospitals. The questionnaires asked about the use of sedatives, analgesics and
NMBAs in patients on mechanical ventilation in the ICU. RESULTS: Forty-nine
questionnaires were received from a possible 53 ICUs with ventilators (response
rate 92.5%). Sedatives and analgesics were given to patients on mechanical
ventilation at virtually all the ICUs surveyed (60% used the combination
routinely). The frequency of use was influenced by both the level of ventilatory
support and the type of underlying disease. Opioids, benzodiazepines and propofol
were employed most commonly, in particular by continuous infusion. NMBAs were
used in 65% of the ICUs surveyed in less than 20% of the total number of patients
in the respective ICU. Overall 98% of the ICUs reported the occurrence of some
kind of side effect secondary to the sedative treatment, but in most ICUs they
were reported to occur in less than 20% of the patients. CONCLUSION: Sedatives
and analgesics are widely used in patients requiring mechanical ventilation in
Danish ICUs. NMBAs are only used in a few patients. The frequency of use is
correlated to the level of ventilatory support required and to the kind of
respiratory disease.
PMID- 10193547
TI - Prognostic performance and customization of the SAPS II: results of a multicenter
Austrian study. Simplified Acute Physiology Score.
AB - OBJECTIVES: To evaluate the prognostic performance of the original Simplified
Acute Physiology Score (SAPS) II in Austrian intensive care patients and to
evaluate the impact of customization. DESIGN: Analysis of the database of a
multicenter study. SETTING: Nine adult medical, surgical, and mixed intensive
care units (ICUs) in Austria. PATIENTS: A total of 1733 patients consecutively
admitted to the ICUs. MEASUREMENTS AND RESULTS: The database included admission
data, SAPS II, length of stay, and hospital mortality. The Hosmer-Lemeshow
goodness-of-fit test for the SAPS II showed a lack of uniformity of fit (H =
89.1, 10 df, p < 0.0001; C = 91.8, 10 df, p < 0.0001). Subgroup analysis showed
good performance in patients with cardiovascular (medical and surgical) diseases
as the primary reasons for admission. A new predictive equation was derived by
means of the logistic regression. Goodness-of-fit was excellent for the
customized model (SAPS IIAM) (H = 11.2, 9 df, p = 0.33, C = 11.6, 9 df, p =
0.24). The mean standardized mortality ratio (SMR) changed from 0.81 +/- 0.26 to
0.93 +/- 0.29 with customization. CONCLUSIONS: SAPS II was not well calibrated
when applied to all patients. However, it performed well for patients with
cardiovascular diseases as the primary reason for admission and may thus be
applied to these patients. Standardized mortality ratios that are calculated from
scoring systems without known calibration must be viewed with skepticism.
PMID- 10193548
TI - Epidemiological features and prognosis of severe community-acquired pneumococcal
pneumonia.
AB - OBJECTIVE: To describe risk factors of severe pneumococcal community-acquired
pneumonia and to study variables influencing outcome. DESIGN: Retrospective (1987
1992) and prospective (1993-1995) study. SETTING: Three participating ICUs from
primary care hospitals. PATIENTS: Five hundred and five patients (mean age: 63 +/
17 years) with severe community-acquired pneumonia (CAP). Three groups of
patients were defined: pneumococcal CAP (group 1), CAP with microbial diagnosis
other than Streptococcus pneumoniae (group 2), CAP from group 2 and CAP without
microbial diagnosis (group 3). MEASUREMENTS AND RESULTS: Admission data and data
on the disease's course were recorded. The mean Simplified Acute Physiologic
Score (SAPS) was 12.5 +/- 5.4. On admission 288 (57 %) patients were mechanically
ventilated (mv) and 82 (16.2 %) required inotropic support. A microbial diagnosis
was established for 309 (61.2%) patients. S. pneumoniae was isolated in 137
(27.1%) patients. Severe pneumococcal CAP was independently associated with male
sex (p = 0.01), lack of antibiotics use before admission (p = 0.0001), non
aspiration pneumonia (p = 0.01) and septic shock (p = 0.0001). The overall
mortality rate was 27.5 % (29.2 % in group 1). In patients with severe
pneumococcal CAP, multivariate analysis showed that leukopenia less than
3,500/mm3 (p = 0.0004), age over 65 years (p = 0.01), septic shock (p = 0.01),
sepsis related complications (p = 0.0001), ICU complications (p = 0.001) and
inadequacy of antimicrobial therapy (p = 0.002) worsened the prognosis.
CONCLUSIONS: Few features facilitate the identification of pneumococcal CAP on
ICU admission. The prognosis is mostly related to severity of illness
(leukopenia, septic shock) while comorbidities do not seem to influence outcome.
Sepsis-related disorders, ICU complications and adequate antimicrobial
chemotherapy are the major variables affecting the outcome during an ICU stay.
PMID- 10193549
TI - D-dimer assay predicts mortality in critically ill patients without disseminated
intravascular coagulation or venous thromboembolic disease.
AB - OBJECTIVE: To determine if D-dimer predicts outcomes in critically ill patients.
DESIGN: Observational, cohort study. SETTING: Medical intensive care unit (MICU)
of a tertiary care hospital. PATIENTS AND PARTICIPANTS: Seventy-four patients
consecutively admitted to the MICU. INTERVENTIONS: D-dimer was measured by latex
agglutination within 12 h of admission to the MICU. MEASUREMENTS AND RESULTS: Of
the study population, 43.2% had positive D-dimers. The in-hospital mortality rate
in D-dimer positive patients was 28.1% as compared to 7.1% in D-dimer negative
subjects (p = 0.024). D-dimer positive patients had significantly greater
frequencies of venous thromboses (21.9% vs 4.8%, p = 0.035). CONCLUSIONS: The D
dimer assay identifies patients at increased risk for mortality and may be a more
sensitive test to determine the presence of underlying microvascular pathology in
critically ill patients. A positive D-dimer at admission to the MICU is
associated with an increased risk for the later development of a venous
thromboembolic event (VTE).
PMID- 10193550
TI - Does bronchial thermodilution allow estimation of cardiac output?
AB - OBJECTIVE: Transcapillary heat transfer after injections of cold saline into the
right atrium generates bronchial thermodilution curves resembling those observed
in the aorta. Under the assumption that no indicator is lost or gained within the
pulmonary capillary bed and changes in blood temperature are instantaneously
recorded in the bronchial system, we tested the hypothesis that flow rates
calculated from bronchial temperature-time curves are similar to those from
aortic curves. DESIGN: Comparative study of two cardiac output estimates in five
dogs. SETTING: Research laboratory for Experimental Anaesthesiology.
INTERVENTIONS: Cardiac output was decreased (repeated withdrawal of blood) and
increased (infusion of colloids or dobutamine) in order to study a wide range of
cardiac outputs. MEASUREMENTS AND RESULTS: Thermistors were placed in a
bronchiole (wedge position) and in the ascending aorta of anaesthetized dogs.
Bronchial and aortic thermodilution curves were recorded after injection of 5 ml
ice-cold saline into the right atrium. We found that bronchial thermodilution
yields flow estimates similar to those from aortic curves. Correlation between
the two flow estimates was acceptable (r = 0.84) with a mean difference between
the two of less than 2%. CONCLUSION: We conclude that the Stewart-Hamilton
equation may be extended to bronchial temperature-time curves for estimations of
cardiac output. At this time, however, we do not advocate bronchial thermistors
as suitable and less invasive alternatives to pulmonary arterial catheters for
routine cardiac output measurements in patients.
PMID- 10193551
TI - Extravascular lung water and intrathoracic blood volume: double versus single
indicator dilution technique.
AB - OBJECTIVE: The accuracy of single thermodilution was assessed in measuring
extravascular lung water (EVLW) and intrathoracic blood volume (ITBV). DESIGN:
Single thermodilution (ST) was prospectively compared with thermo-dye dilution
(TD) in 13 mechanically ventilated pigs using the Pulsion Cold Z-021 monitor.
INTERVENTIONS: Lung injury was induced with oleic acid injection. RESULTS:
EVLWI(TD) increased from 4.3 +/- 1.4 to 11.3 +/- 4.5 ml/kg (p = 0.0014) and
ITBV(TD) decreased from 581 +/- 66 to 540 +/- 85 ml (p = 0.039) after induction
of lung injury. EVLW(ST) was systematically overestimated (0.5-1 ml/kg) and
ITBV(ST) was slightly underestimated (15-20 ml) when calculated automatically by
the Pulsion Cold Z-021 monitor. This bias could be removed by adjusting two
coefficients needed for the computation of ITBV(ST) and EVLW(ST) so that the
following regression equations were obtained: EVLWI(ST) = 0.98 EVLWI(TD) + 0.27
(r = 0.94, p < 10(-6)) and ITBV(ST) = 1.0 x ITBV(TD) + 0 (r = 0.87, p < 10(-6)).
CONCLUSIONS: Single thermodilution allows estimation of ITBV and EVLW values with
reasonable accuracy and therefore provides useful information about the cardiac
preload and the severity of lung injury. However, automatic calculation of
EVLWI(ST) and ITBV(ST) using the Pulsion Cold Z-021 might be biased. Therefore,
researchers and clinicians should validate single thermodilution for the given
settings, before employing this method to estimate EVLW and ITBV.
PMID- 10193552
TI - Moderately severe anaphylactoid reaction to pentastarch (200/0.5) in a patient
with acute severe asthma.
AB - The use of synthetic colloids for resuscitation and volume replacement is common
in the intensive care unit. Although adverse reactions have been reported to
colloid solutions, the incidence of severe reactions to the starch derivatives is
low. We report a case of an anaphylactoid reaction to pentastarch (200/0.5) in a
young asthmatic who received it as a fluid challenge in the intensive care unit.
The pathogenesis and implications of such a reaction in an asthmatic are
discussed.
PMID- 10193553
TI - Successful treatment of severe myocardial failure after postpartum haemorrhage
with the use of an intra-aortic balloon pump.
AB - We report a 29-year-old primigravid who developed cardiac failure following
postpartum haemorrhage unresponsive to volume resuscitation and therapy with
catecholamines and phosphodiesterase-inhibitors. Transoesophageal
echocardiography (TEE) demonstrated left atrial and ventricular dilatation and
global left ventricular hypokinesis. No elevation of serum MB-isoenzyme fraction
was detected and other organ functions remained stable. Although emergency
cardiac transplantation was considered in the presented patient, the institution
of intra-aortic counterpulsation was decided on as a first treatment option.
Intra-aortic balloon counter-pulsation rapidly improved cardiac function and led
to weaning from pharmacological cardiac support within a few days. Mechanical
circulatory assist devices can be life-saving in postpartum-haemorrhage
associated cardiac failure.
PMID- 10193554
TI - ARDS in a patient with homozygous beta-thalassemia due to yersiniosis.
AB - We report a case of Yersinia enterocolitica sepsis syndrome and the acute
respiratory distress syndrome in a chronically transfused adolescent with beta
thalassemia. This manifestation of serious Y. enterocolitica infection has not
previously been reported. Dyspnea, hypoxia, and fever were the principal features
of the clinical presentation. The acute onset of respiratory symptoms occurred
after appendectomy. Chest radiographs revealed frontal bilateral infiltrates and
alveolar consolidation to three quadrants. Y. enterocolitica was identified from
blood and intraoperative appendix cultures. Although there was no need for
mechanical ventilation, a remarkable persistence of clinical and X-ray findings
was noted. Therapy with high levels of oxygen, and intravenous amikacin and
piperacillin/tazobactam led to a favorable outcome.
PMID- 10193555
TI - Bronchodilators in the ICU.
PMID- 10193556
TI - Inhalation therapy during mechanical ventilation.
PMID- 10193557
TI - Ventilator-induced lung inflammation: is it always harmful?
PMID- 10193558
TI - Community-acquired methicillin-resistant Staphylococcus aureus right-sided
infective endocarditis in a non-addict patient with ventricular septal defect.
PMID- 10193559
TI - Septic shock caused by Mycobacterium tuberculosis in a non-HIV patient.
PMID- 10193560
TI - Management of intra-thecal baclofen overdose.
PMID- 10193561
TI - Comparison of the breathing workload imposed by different ventilators.
PMID- 10193562
TI - Predicting bronchopulmonary dysplasia.
PMID- 10193563
TI - Atrial tachyarrhythmia after cardiac surgery.
PMID- 10193564
TI - Atrial tachyarrhythmia after cardiac surgery: role of magnesium infusion.
PMID- 10193565
TI - Vasogenic oedema and brain trauma.
PMID- 10193566
TI - The Omega system can underestimate medical activity in the ICU.
PMID- 10193567
TI - Hemodynamic profile in severe ARDS.
PMID- 10193568
TI - Molecular mechanisms of the copper dependent oxidation of low-density
lipoprotein.
AB - There is little doubt that oxidative modification of low-density lipoprotein
(LDL) is an important process during atherogenesis. This conclusion has been
derived in a relatively short period of time since the initial descriptions of
LDL oxidation with a significant contribution from Professor Esterbauer and
colleagues. In this short overview, we have described the mechanisms by which
copper promotes LDL oxidation focussing on the importance of lipid hydroperoxides
in this process. These mechanisms are discussed in the context of the ongoing
debate as to relevance of metal dependent LDL oxidation in vivo and as a model
reaction for assessing antioxidants.
PMID- 10193569
TI - Glutathione (GSH) and the toxicity of oxidised low-density lipoprotein to human
monocyte-macrophages.
AB - Macrophage death, believed to be an important event in the pathogenesis of human
atherosclerosis, can be induced by oxidised low-density lipoprotein (LDL) in
vitro. Supplementation of the culture medium with 5 mM GSH significantly
protected human monocyte-macrophages in vitro against the toxicity of copper
oxidised LDL. Oxidation products of LDL include the aldehyde 4-hydroxynonenal
(HNE). We present evidence that conjugation of HNE by GSH contributes to this
protection. In the absence of cells, HPLC analysis showed there were marked
reductions in the levels of both pure HNE and HNE in copper-oxidised LDL in the
presence of GSH. However, GSH did not reverse protein modification, as judged by
agarose gel electrophoresis, nor did it influence the depletion of
polyunsaturated fatty acids, which were assessed using gas chromatography. The
possible implications for human atherosclerosis are discussed.
PMID- 10193570
TI - Effective inhibition by beta-carotene of cellular DNA breaking induced by
peroxynitrous acid.
AB - Peroxynitrous acid synthesized by reaction of hydrogen peroxide and nitrite and
generated from 3-morpholinosydononimine (SIN-1) induced cellular DNA breaking of
human promyelocytic leukemia HL-60 cells in phosphate buffer (pH 7.5) as assessed
by alkaline single cell gel electrophoresis (comet) assay and quantification of
comet types. Ascorbate and Trolox inhibited cellular DNA breaking induced by
peroxynitrous acid, but the concentrations of these antioxidants required for
effective inhibition was about 50-fold higher than that of peroxynitrous acid.
beta-Carotene protected DNA breaking by peroxynitrous acid in 20% tetrahydrofuran
phosphate buffer (pH 7.5) much more effectively than ascorbate and Trolox. The
concentrations of beta-carotene required for effective inhibition was lower than
the concentration of peroxynitrous acid.
PMID- 10193571
TI - Dexamethasone ameliorates oxidative DNA damage induced by benzene and LPS in
mouse bone marrow.
AB - Mice were grouped to receive vehicle, dexamethasone (DEX), lipopolysaccharide
(LPS), benzene (BZ, 200 mg/kg) and combinations: LPS + DEX, BZ + DEX, LPS + BZ,
LPS + DEX + BZ. The DNA damage in bone marrow cells from BZ group was enhanced
2.8-fold measured by nuclear 8-hydroxy-2 '-deoxyguanosine (8-oxodG) and 1.4-fold
measured by Comet score (index of DNA breaks) (p < 0.05). In the BZ + DEX group,
8-oxodG level and the Comet score were lowered to 65% and 76% respectively of
that in the BZ group (p < 0.05). The BZ + LPS caused a 3.9-fold increase in 8
oxodG and a 1.6-fold increase in the Comet score (p < 0.05). The LPS + DEX + BZ
lowered 8-oxodG level and the Comet score to 50% and 78% of the values in the LPS
+ BZ group, respectively (p < 0.05). Nitrate/nitrite levels in serum were higher
after BZ + LPS treatment than after all other treatments. Both 8-oxodG level and
the Comet scores were correlated to the serum nitrate/nitrite level across all
the treatments (r = 0.55, p < 0.01 and r = 0.69, p < 0.01, respectively). In bone
marrow cells the 8-oxodG correlated with the Comet scores (r = 0.80, p < 0.01).
We conclude that DEX administration can reduce the DNA damage from BZ treatment
and from the combination of BZ and LPS. The correlation of DNA damage with
nitrate/nitrite indicates the possible involvement of reactive nitrogen species
(RNS) in the interaction between BZ and the inflammatory reaction stimulated by
LPS. The 8-oxodG determination is more sensitive than strand break analysis by
the Comet assay in bone marrow in vivo in mice for measuring the BZ-induced DNA
damage.
PMID- 10193573
TI - Differences in the reactivity of phthalic hydrazide and luminol with hydroxyl
radicals.
AB - The reactivity of 5-amino-2,3-dihydro-phthalazine-1,4-dione (luminol) and
phthalic hydrazide with hydroxyl radicals was studied. HO*-radicals were
generated by the Fenton reaction as well as by water radiolysis. Both luminol and
phthalic hydrazide react with hydroxyl radicals under intense chemiluminescence
(CL) emission. However, exclusively the CL arising from phthalic hydrazide
oxidation can be quenched by competition (e.g. by the addition of carbohydrates),
whereas luminol CL is enhanced. The reactivities of both compounds with HO*
radicals were further studied by time-resolved spectroscopy (pulse radiolysis),
competition methods, NMR spectroscopy and mass spectrometry. Whereas only slight
differences were detectable by pulse radiolysis, the analysis of competition
kinetics in the presence of p-nitroso-dimethylaniline (NDMA) gave a two-fold
enhanced reactivity for luminol (4.8 x 10(9) l mol(-1) s(-1)) in comparison to
phthalic hydrazide (2.0 x 10(9) l mol(-1) s(-1)). NMR and mass spectrometric
analyses revealed significant differences in the reactivity of HO*-radicals:
whereas in luminol solutions hydroxylation of the aromatic ring system
predominated, hydroxylated products were not detectable upon irradiation of
phthalic hydrazide. A hypothetical mechanism is proposed which may explain the
observed differences.
PMID- 10193572
TI - Effect of beta-carotene on the transformation of tyrosine by nitrogen dioxide and
peroxynitrous acid.
AB - In the NO2-exposure of tyrosine in 70% dioxane/phosphate buffer (pH 7.4), beta
carotene enhanced the degradation of tyrosine and/or 3-nitrotyrosine produced,
whereas alpha-tocopherol and ascorbyl palmitate inhibited the transformation of
tyrosine into 3-nitrotyrosine. Generation of certain active species in the
interaction of beta-carotene with NO2 was suggested. Ascorbyl palmitate
effectively and alpha-tocopherol slightly inhibited the transformation of
tyrosine in the NO2-exposure in the presence of beta-carotene. In the reaction of
tyrosine with ONOO-/ONOOH, beta-carotene enhanced the degradation of 3
nitrotyrosine produced suggesting generation of certain active species, whereas
alpha-tocopherol and ascorbyl palmitate completely suppressed the transformation
of tyrosine into 3-nitrotyrosine.
PMID- 10193574
TI - Antioxidant BO-653 and human macrophage-mediated LDL oxidation.
AB - Oxidation of LDL is now widely accepted to be involved in atherogenesis. The aim
of this study was to examine the effect of BO-653, a strong radical scavenger and
antioxidant, on oxidation of LDL by human macrophages in vitro. Fifty microg/ml
LDL protein was incubated with macrophages in Ham's F10 medium, supplemented with
additional Fe2+, for up to 48 h. Then the medium was analysed by LDL agarose gel
electrophoresis, the thiobarbituric acid assay and gas chromatography. In the
absence of added exogenous antioxidants, after 24h LDL oxidation produced 30.48
nmoles MDA equivalents/mg LDL protein and a relative electrophoretic mobility of
4.74. Linoleic acid (18:2), arachidonic acid (20:4) and cholesterol were depleted
and 7beta-hydroxycholesterol was generated. BO-653 completely inhibited this cell
mediated oxidation of LDL in concentrations as low as 5 microM, being more
effective than either alpha-tocopherol or probucol, which completely inhibited
oxidation at 200 and 80 microM and only partially at 80 and 8 microM,
respectively. This inhibition of cell-mediated LDL oxidation was not due to
toxicity, as alpha-tocopherol, probucol and BO-653 were not toxic for the
macrophages at the concentrations tested. Eighty microM alpha-tocopherol, 8
microM probucol and 5 microM BO-653 significantly reduced the toxicity to the
oxidising culture caused by LDL oxidation. The results show that in this system
BO-653 is a more effective antioxidant than alpha-tocopherol or probucol.
PMID- 10193575
TI - Hydrogen peroxide-induced apoptosis in HL-60 cells requires caspase-3 activation.
AB - Apoptosis has been associated with oxidative stress in biological systems.
Caspases have been considered to play a pivotal role in the execution phase of
apoptosis. However, which caspases function as executioners in reactive oxygen
species (ROS)-induced apoptosis is not known. The present study was performed to
identify the major caspases acting in ROS-induced apoptosis. Treatment of HL-60
cells with 50 microM hydrogen peroxide (H2O2) for 4 h induced the morphological
changes such as condensed and/or fragmented nuclei, increase in caspase-3
subfamily protease activities, reduction of the procaspase-3 and a DNA
fragmentation. To determine the role of caspases in H2O2-induced apoptosis,
caspase inhibitors, acetyl-Tyr-Val-Ala-Asp-chloromethyl ketone (Ac-YVAD-cmk),
acetyl-Asp-Glu-Val-Asp-aldehyde (Ac-DEVD-CHO) and acetyl-Val-Glu-Ile-Asp-aldehyde
(Ac-VEID-CHO), selective for caspase-1 subfamily, caspase-3 subfamily and caspase
6, respectively, were loaded into the cells using an osmotic lysis of pinosomes
method. Of these caspase inhibitors, only Ac-DEVD-CHO completely blocked
morphological changes, caspase-3 subfamily protease activation and DNA ladder
formation in H2O2-treated HL-60 cells. This inhibitory effect was dose-dependent.
These results suggest that caspase-3, but not caspase-1 is required for
commitment to ROS-triggered apoptosis.
PMID- 10193576
TI - N-acetylcysteine increases the biosynthesis of recombinant EPO in apoptotic
Chinese hamster ovary cells.
AB - Sodium butyrate (NaBu) is known to enhance the rate of biosynthesis of
recombinant proteins in Chinese hamster ovary cells (CHO). Here we demonstrate
that supplementation with NaBu during rapid growth brings about abrupt death of
the cells. The death of the cells is due to apoptosis, as assessed by
intranucleosomal DNA fragmentation. The promotion of apoptotic death of the cells
could be partially blocked by treatment with the well-known antioxidant, N
acetylcysteine (NAC). Strikingly, the NAC treatment enhanced the production of
recombinant EPO two-fold compared with that of the culture without NAC
supplementation. These results showed that NaBu treatment supplemented with NAC
not only inhibits apoptosis, but also exerts a synergistic effect on the
biosynthesis of recombinant EPO.
PMID- 10193577
TI - Enhancement of myeloid cell growth by benzene metabolites via the production of
active oxygen species.
AB - In low concentrations, benzene and its metabolite hydroquinone are known to have
diverse biological effects on cells, including the synergistic stimulation with
GM-CSF of hematopoietic colony formation in vitro, stimulation of granulocytic
differentiation in vitro and in vivo, and general suppression of hematopoiesis in
vivo. These chemicals are also known to be active in the induction of active
oxygen species. We used several assays to determine the effects of benzene
metabolites (hydroquinone, benzenetriol, benzoquinone) and active oxygen species
(xanthine/xanthine oxidase) on cell growth and cell cycle kinetics of the human
myeloid cell line HL-60. HL-60 cells treated with these chemicals for 2 h in PBS
showed increased growth over untreated controls in a subsequent 18h growth period
in complete media. Incorporation of 3H-thymidine was also increased
proportionately by these treatments. Catalase treatment abrogated the increased
cell growth of all chemicals, suggesting an oxidative mechanism for the effect of
all treatments alike. Cell cycle kinetics assays showed that the growth increase
was caused by an increased recruitment of cells from G0/G1 to S-phase for both
hydroquinone and active oxygen, rather than a decrease in the length of the cell
cycle. Benzene metabolite's enhancement of growth of myeloid cells through an
active oxygen mechanism may be involved in a number of aspects of benzene
toxicity, including enhanced granulocytic growth and differentiation, stimulation
of GM-CSF-induced colony formation, apoptosis inhibition, and stimulation of
progenitor cell mitogenesis in the bone marrow. These effects in sum may be
involved in the benzene-induced "promotion" of a clonal cell population to the
fully leukemic state.
PMID- 10193578
TI - Inactivation of myocardial dihydrolipoamide dehydrogenase by myeloperoxidase
systems: effect of halides, nitrite and thiol compounds.
AB - Dihydrolipoamide dehydrogenase (LADH) lipoamide reductase activity decreased
whereas enzyme diaphorase activity increased after LADH treatment with
myeloperoxidase (MPO) dependent systems (MPO/H2O2/halide, MPO/NADH/halide and
MPO/H2O2/nitrite systems. LADH inactivation was a function of the composition of
the inactivating system and the incubation time. Chloride, iodide, bromide, and
the thiocyanate anions were effective complements of the MPO/H2O2 system. NaOCl
inactivated LADH, thus supporting hypochlorous acid (HOCl) as putative agent of
the MPO/H2O2/NaCl system. NaOCl and the MPO/H2O2/NaCl system oxidized LADH thiols
and NaOCl also oxidized LADH methionine and tyrosine residues. LADH inactivation
by the MPO/NADH/halide systems was prevented by catalase and enhanced by
superoxide dismutase, in close agreement with H2O2 production by the LADH/NADH
system. Similar effects were obtained with lactoperoxidase and horse-radish
peroxidase supplemented systems. L-cysteine, N-acetylcysteine, penicillamine, N
(2-mercaptopropionylglycine), Captopril and taurine protected LADH against MPO
systems and NaOCl. The effect of the MPO/H2O2/NaNO2 system was prevented by MPO
inhibitors (sodium azide, isoniazid, salicylhydroxamic acid) and also by L
cysteine, L-methionine, L-tryptophan, L-tyrosine, L-histidine and reduced
glutathione. The summarized observations support the hypothesis that peroxidase
generated "reactive species" oxidize essential thiol groups at LADH catalytic
site.
PMID- 10193579
TI - Relation between natriuresis and urinary excretion of hydrogen peroxide.
AB - Changes in the urinary hydrogen peroxide by exercise or salt load were studied in
six healthy male volunteers. Exercise was performed by bicycle ergometer for 30
min at the intensity of 80% of the maximum heart rate predicted by age. Urinary
excretion rate of hydrogen peroxide showed a tendency to increase in the salt
load experiment, and to decrease by exercise. Correlation coefficient between
urinary excretion rate of sodium and hydrogen peroxide one hour after the load
was 0.797 (0.1 > p > 0.05) in the exercise experiment, 0.892 (p <0.05) in the
salt load experiment and 0.877 (p < 0.001) in both experiments. Correlation
coefficient between area under the curve for sodium excretion and hydrogen
peroxide excretion was also as high as 0.822 (p < 0.05) in the exercise
experiment, 0.909 (p < 0.05) in the salt load experiment and 0.853 (p < 0.001) in
both experiments. These results may suggest that urinary excretion rate of
hydrogen peroxide is closely related to metabolism of electrolytes and fluid in
the renal tubules.
PMID- 10193580
TI - Analysis of the oxidative stress response of Penicillium chrysogenum to
menadione.
AB - The intracellular superoxide and glutathione disulphide concentrations increased
in Penicillium chrysogeum treated with 50, 250 or 500 microM menadione (MQ). A
significant increase in the intracellular peroxide concentration was also
observed when mycelia were exposed to 250 or 500 microM MQ. The specific activity
of Cu,Zn and Mn superoxide dismutases, glutathione reductase and glutathione S
transferase as well as the glutathione producing activity increased in the
presence of MQ while glutathione peroxidase and gamma-glutamyltranspeptidase were
only induced by high intracellular peroxide levels. The glucose-6-phosphate
dehydrogenase and catalase activities did not respond to the oxidative stress
caused by MQ.
PMID- 10193581
TI - Mechanisms underlying gastric antiulcerative activity of nitroxides in rats.
AB - Reactive oxygen-derived species and redox-active metals are implicated in
mediation of the pathogenesis of gastric mucosal damage and ulceration.
Therefore, common strategies of intervention employ metal chelators,
antioxidative enzymes, and low-molecular-weight antioxidants (LMWA). The aim of
the present study was to elaborate the mechanism(s) responsible for the
protection provided by nitroxide radicals in the experimental model of gastric
ulceration. Fasted male rats were treated ig with 1 ml 96% ethanol, with or
without ig pretreatment with nitroxide or hydroxylamine. In several experiments,
rats were injected ip or iv with iron(III) or iron(II) prior to ethanol
administration. Rats were sacrificed 10 min after ethanol administration, the
stomach was removed, washed and lesion area measured. Pretreatment with iron(III)
complexed to nitrilotriacetate or citrate, aggravated the extent of the gastric
injury. Conversely, iron(II) inhibited the formation of lesions. The nitroxides
were rapidly reduced to their respective hydroxylamines and demonstrated
antiulcerative activity for rats treated with iron. However, injecting the
hydroxylamine resulted in a similar tissue distribution of
nitroxide/hydroxylamnine but did not provide protection. The results show that:
(a) the nitroxide radicals, rather than their respective non-radical reduced
form, are the active species responsible for protection; (b) nitroxides protect
by dismutating O2*- and possibly indirectly increasing the NO level; (c) unlike
classical LMWA which are reducing agents, nitroxides inhibit gastric damage by
acting as mild oxidants, oxidizing reduced metals and pre-empting the Fenton
reaction; and (d) the nitroxides act catalytically as recycling antioxidants.
PMID- 10193582
TI - Lycopene and beta-carotene protect against oxidative damage in HT29 cells at low
concentrations but rapidly lose this capacity at higher doses.
AB - Epidemiological studies have clearly demonstrated a link between dietary
carotenoids and the reduced incidence of certain diseases, including some
cancers. However recent intervention studies (e.g. ATBC, CARET and others) have
shown that beta-carotene supplementation has little or no beneficial effect and
may, in fact, increase the incidence of lung cancers in smokers. This presents a
serious dilemma for the scientific community - are carotenoids at high
concentrations actually harmful in certain circumstances? Currently, a
significant number of intervention studies are on-going throughout the world
involving carotenoids (of both natural and synthetic origin). Our approach has
been to study the ability of supplementary carotenoids in protecting cells
against oxidatively-induced DNA damage (as measured by the comet assay), and
membrane integrity (as measured by ethidium bromide uptake). Both lycopene and
beta-carotene only afforded protection against DNA damage (induced by
xanthine/xanthine oxidase) at relatively low concentrations (1-3 microM). These
levels are comparable with those seen in the plasma of individuals who consume a
carotenoid-rich diet. However, at higher concentrations (4-10 microM), the
ability to protect the cell against such oxidative damage was rapidly lost and,
indeed, the presence of carotenoids may actually serve to increase the extent of
DNA damage. Similar data were obtained when protection against membrane damage
was studied. This would suggest that supplementation with individual carotenoids
to significantly elevate blood and tissue levels is of little benefit and, may,
in fact, be deleterious. This in vitro data presented maybe significant in the
light of recent intervention trials.
PMID- 10193583
TI - The polyphenolic content of fruit and vegetables and their antioxidant
activities. What does a serving constitute?
AB - Analysis of the major flavone, flavonol, anthocyanidin and hydroxycinnamic acid
constituents (and their glycosides) of onion, tomato, egg plant and apple has
been undertaken and the antioxidant activities of the phenolic extracts
determined. The major phenolic antioxidant components of egg plant are
chlorogenic acid in the flesh and a delphinidin conjugate in the skin. In the
case of apple, the major phenolic antioxidants detected are chlorogenic acid,
procyanidins/catechin compounds, rutin and phloridzin. Quercetin glycosides are
well-known to be the major phenolic components of onion. Assessment of the
antioxidant activities of a serving of 100g fresh weight fruit, vegetable and
comparison with previously reported findings for 150 ml beverage (500 ml portion
in the case of beer), expressed in micromol Trolox equivalents show that the
antioxidant activities of 1 glass (150 ml) red wine equivalent to 12 glasses
white wine equivalent to 2 cups of tea equivalent to 4 apples equivalent to 5
portions of onion equivalent to 5.5 portions egg plant equivalent to 3.5 glasses
of blackcurrant juice equivalent to 3.5 (500 ml) glasses of beer equivalent to 7
glasses of orange juice equivalent to 20 glasses of apple juice (long life).
PMID- 10193584
TI - End-of-life care and family practice.
PMID- 10193585
TI - Use of breakfast cereals for constipation in elderly persons.
PMID- 10193586
TI - Increased incidence of prostate cancer in black patients.
PMID- 10193587
TI - The hospitalist debate.
PMID- 10193588
TI - The hospitalist debate.
PMID- 10193589
TI - Primary prevention of CHD: nine ways to reduce risk.
AB - Lowering cholesterol can reduce the incidence of coronary heart disease. Treating
hypertension reduces overall mortality and is most effective in reducing the risk
of coronary heart disease in older patients. Smoking cessation reduces the level
of risk to that of nonsmokers within about three years of cessation. Aspirin is
likely to be an effective means of primary prevention, but a group in whom
treatment is appropriate has yet to be defined. Evidence that supplementation
with vitamin A or C reduces the risk of coronary heart disease is inadequate; the
data for use of vitamin E are inconclusive. Epidemiologic evidence is sufficient
to recommend that most persons increase their levels of physical activity.
Lowering homocysteine levels through increased folate intake is a promising but
unproven primary prevention strategy. Hormone replacement therapy was associated
with reduced incidence of coronary heart disease in epidemiologic studies but was
not effective in a secondary prevention trial.
PMID- 10193590
TI - Pediatric urinary tract infection and reflux.
AB - Urinary tract infections in children are sometimes associated with vesicoureteral
reflux, which can lead to renal scarring if it remains unrecognized. Since the
risk of renal scarring is greatest in infants, any child who presents with a
urinary tract infection prior to toilet training should be evaluated for the
presence of reflux. Children who may be lost to follow-up and those who have
recurrent urinary tract infections should also be evaluated. The preferred method
for evaluation of urinary reflux is a voiding cystourethrogram. Documented reflux
is initially treated with prophylactic antibiotics. Patients who have
breakthrough infections on prophylaxis, develop new renal scarring, have high
grade reflux or cannot comply with long-term antibiotic prophylaxis should be
considered for surgical correction. The preferred method of surgery is ureteral
reimplantation. A newer method involves injection of the bladder trigone with
collagen.
PMID- 10193591
TI - Amyotrophic lateral sclerosis: Lou Gehrig's disease.
AB - Amyotrophic lateral sclerosis (ALS), commonly called Lou Gehrig's disease, is a
progressive neuromuscular condition characterized by weakness, muscle wasting,
fasciculations and increased reflexes. Approximately 30,000 Americans currently
have the disease. The annual incidence rate is one to two cases per 100,000. The
disease is most commonly diagnosed in middle age and affects more men than women.
It usually presents with problems in dexterity or gait resulting from muscle
weakness. Difficulty in speaking or swallowing is the initial symptom in the
bulbar form of the disease. Over a period of months or years, patients with ALS
develop severe, progressive muscular weakness and other symptoms caused by loss
of function in both upper and lower motor neurons. Sphincter control, sensory
function, intellectual abilities and skin integrity are preserved. Patients
become completely disabled, often requiring ventilatory support and gastrostomy.
Death usually occurs within five years of diagnosis and is attributed to
respiratory failure or cachexia. The etiology of the disease is unknown. Current
research is focused on abnormalities of neuronal cell metabolism involving
glutamate and the role of potential neurotoxins and neurotrophic factors. New
drugs are being developed based on these theories. Current management involves
aggressive, individualized alleviation of symptoms and complications.
PMID- 10193592
TI - Evaluation and treatment of patients with suicidal ideation.
AB - Suicidal ideation is more common than completed suicide. Most persons who commit
suicide have a psychiatric disorder at the time of death. Because many patients
with psychiatric disorders are seen by family physicians and other primary care
practitioners rather than by psychiatrists, it is important that these
practitioners recognize the signs and symptoms of the psychiatric disorders
(particularly alcohol abuse and major depression) that are associated with
suicide. Although most patients with suicidal ideation do not ultimately commit
suicide, the extent of suicidal ideation must be determined, including the
presence of a suicide plan and the patient's means to commit suicide.
PMID- 10193593
TI - Adult circumcision.
AB - Adult circumcision can be performed under local or regional anesthesia. Medical
indications for this procedure include phimosis, paraphimosis, recurrent
balanitis and posthitis (inflammation of the prepuce). Nonmedical reasons may be
social, cultural, personal or religious. The procedure is commonly performed
using either the dorsal slit or the sleeve technique. The dorsal slit is
especially useful in patients who have phimosis. The sleeve technique may provide
better control of bleeding in patients with large subcutaneous veins. A dorsal
penile nerve block, with or without a circumferential penile block, provides
adequate anesthesia. Informed consent must be obtained. Possible complications of
adult circumcision include infection, bleeding, poor cosmetic results and a
change in sensation during intercourse.
PMID- 10193594
TI - Taking a nutrition history: a practical approach for family physicians.
AB - The association between nutrition and health has been clearly documented. Primary
care physicians are expected to address nutrition and dietary behavior issues
with their patients in the context of a brief clinical encounter. This article
proposes the use of a short interview form, with specific suggestions for
behavior changes that family physicians can use to help their patients meet
currently accepted dietary guidelines. Answers to the questions on the interview
form provide the physician with an overall sense of the patient's daily eating
habits and help to identify major sources of saturated fat in the patient's diet.
The patient is asked about the number of meals and snacks eaten in a 24-hour
period, dining-out habits and frequency of consumption of fruits, vegetables,
meats, poultry, fish, dairy products and desserts. Documentation of dietary
changes can be accomplished using the suggested nutrition history form, and
improvements in nutritional status can be measured using weight, blood pressure
and laboratory test data.
PMID- 10193595
TI - Flexible sigmoidoscopy: screening for colorectal cancer.
AB - Flexible sigmoidoscopy is an important screening procedure because of its ability
to detect early changes in the distal colon. The 60-cm flexible sigmoidoscope
provides excellent visualization with minimal discomfort to patients. Successful
sigmoidoscopy requires adequate patient preparation, proper equipment and an
experienced examiner who can recognize both normal and abnormal findings.
Complications arising from sigmoidoscopy are rare, but patients may experience
some cramping, gas or watery stools. Screening and primary preventive measures,
including regular exercise and increased dietary fiber intake, can lower the
morbidity and mortality associated with colorectal cancer.
PMID- 10193596
TI - Vulvodynia and vulvar vestibulitis: challenges in diagnosis and management.
AB - Vulvodynia is a problem most family physicians can expect to encounter. It is a
syndrome of unexplained vulvar pain, frequently accompanied by physical
disabilities, limitation of daily activities, sexual dysfunction and psychologic
distress. The patient's vulvar pain usually has an acute onset and, in most
cases, becomes a chronic problem lasting months to years. The pain is often
described as burning or stinging, or a feeling of rawness or irritation.
Vulvodynia may have multiple causes, with several subsets, including cyclic
vulvovaginitis, vulvar vestibulitis syndrome, essential (dysesthetic) vulvodynia
and vulvar dermatoses. Evaluation should include a thorough history and physical
examination as well as cultures for bacteria and fungus, KOH microscopic
examination and biopsy of any suspicious areas. Proper treatment mandates that
the correct type of vulvodynia be identified. Depending on the specific
diagnosis, treatment may include fluconazole, calcium citrate, tricyclic
antidepressants, topical corticosteroids, physical therapy with biofeedback,
surgery or laser therapy. Since vulvodynia is often a chronic condition, regular
medical follow-up and referral to a support group are helpful for most patients.
PMID- 10193597
TI - Classification of tremor and update on treatment.
AB - Tremor is a symptom of many disorders, including Parkinson's disease, essential
tremor, orthostatic tremor, cerebellar disease, peripheral neuropathy and alcohol
withdrawal. Tremors may be classified as postural, rest or action tremors.
Symptomatic treatment is tailored to the tremor type. Combination therapy with
carbidopa and levodopa remains the first-line approach for parkinsonian tremor.
Essential tremor may be amenable to propranolol or primidone. Propranolol may be
useful in treating alcohol withdrawal tremor, and isoniazid may control the
cerebellar tremor associated with multiple sclerosis. Clonazepam may relieve
orthostatic tremor. Other agents are also available for the treatment of tremor.
When medical therapy fails to control the tremor, surgical options such as
thalamotomy, pallidotomy and thalamic stimulation should be considered in severe
cases. Thalamic stimulation, the most recent of these surgical approaches, offers
the advantage over ablative procedures of alleviating tremor without the creation
of a permanent lesion.
PMID- 10193598
TI - Primary prevention of child abuse.
AB - In 1993, the U.S. Advisory Board on Child Abuse and Neglect declared a child
protection emergency. Between 1985 and 1993, there was a 50 percent increase in
reported cases of child abuse. Three million cases of child abuse are reported in
the United States each year. Treatment of the abuser has had only limited success
and child protection agencies are overwhelmed. Recently, efforts have begun to
focus on the primary prevention of child abuse. Primary prevention of child abuse
is defined as any intervention that prevents child abuse before it occurs.
Primary prevention must be implemented on many levels before it can be
successful. Strategies on the societal level include increasing the "value" of
children, increasing the economic self-sufficiency of families, discouraging
corporal punishment and other forms of violence, making health care more
accessible and affordable, expanding and improving coordination of social
services, improving the identification and treatment of psychologic problems, and
alcohol and drug abuse, providing more affordable child care and preventing the
birth of unwanted children. Strategies on the familial level include helping
parents meet their basic needs, identifying problems of substance abuse and
spouse abuse, and educating parents about child behavior, discipline, safety and
development.
PMID- 10193599
TI - Ambulatory management of common forms of anemia.
AB - Anemia is a prevalent condition with a variety of underlying causes. Once the
etiology has been established, many forms of anemia can be easily managed by the
family physician. Iron deficiency, the most common form of anemia, may be treated
orally or, rarely, parenterally. Vitamin B12 deficiency has traditionally been
treated with intramuscular injections, although oral and intranasal preparations
are also available. The treatment of folate deficiency is straightforward,
relying on oral supplements. Folic acid supplementation is also recommended for
women of child-bearing age to reduce their risk of neural tube defects. Current
research focuses on folate's role in reducing the risk of premature
cardiovascular disease.
PMID- 10193600
TI - Low-molecular-weight heparin in preventing and treating DVT.
AB - Low-molecular-weight heparin is a relatively recent addition to the list of
therapies for prophylaxis and treatment of deep venous thrombosis (DVT). As a
prophylactic, low-molecular-weight heparin is as effective as standard heparin or
warfarin and does not require monitoring of the activated partial thromboplastin
time or the International Normalized Ratio. Traditionally, treatment for DVT
required patients to be hospitalized for administration of intravenous heparin.
With subcutaneous injections of low-molecular-weight heparin, treatment of DVT
can be initiated or completed in the outpatient setting with no increased risk of
recurrent thromboembolism or bleeding complications. Low-molecular-weight heparin
is an attractive option for use in patients with a first episode of DVT, no risk
factors for bleeding and the ability to administer injections with or without the
help of a visiting nurse or family member.
PMID- 10193601
TI - New guidelines offer recommendations for women with epilepsy.
PMID- 10193602
TI - CDC calls for tuberculosis screening and treatment for all patients with HIV
infection.
PMID- 10193603
TI - ACOG releases a statement on identification and treatment of adolescent victims
of sexual assault. American College of Obstetricians and Gynecologists.
PMID- 10193604
TI - Report of 190 consecutive cases of large acoustic tumors (vestibular schwannoma)
removed via the translabyrinthine approach.
AB - OBJECT: The choice of approach for surgical removal of large acoustic neuromas is
still controversial. The authors reviewed the results in a series of patients who
underwent removal of large tumors via the translabyrinthine approach. METHODS:
The authors conducted a database analysis of 190 patients (89 men and 101 women)
with acoustic neuromas 3 cm or greater in size. The mean age of these patients
was 46.1+/-15.6 years. One hundred seventy-eight patients underwent primary
translabyrinthine surgical removal and 12 underwent surgery for residual tumor.
Total tumor removal was accomplished in 183 cases (96.3%). The tumor was adherent
to the facial nerve to some degree in 64% of the cases, but the facial nerve was
preserved anatomically in 178 (93.7%) of the patients. Divided nerves were
repaired by primary attachment or cable graft. Facial nerve function was assessed
immediately after surgery, at the time of discharge, and at 3 to 4 weeks and 1
year after discharge. Excellent function (House-Brackmann facial nerve Grade I or
II) was present in 55%, 33.9%, 38.8%, and 52.6% of the patients for each time
interval, respectively, with acceptable function (Grades I-IV) in 81% at 1 year.
Cerebrospinal fluid leakage that required surgical repair occurred in only 1.1%
of the patients and meningitis in 3.7%. There were no deaths. CONCLUSIONS: Use of
the translabyrinthine approach for removal of large tumors resulted in good
anatomical and functional preservation of the facial nerve, with minimum
incidence of morbidity and no incidence of mortality. The authors continue to
recommend use of this approach for acoustic tumors larger than 3 cm and for
smaller tumors when hearing preservation is not an issue.
PMID- 10193605
TI - Magnetic resonance cisternography used to determine precise topography of the
facial nerve and three components of the eighth cranial nerve in the internal
auditory canal and cerebellopontine cistern.
AB - OBJECT: The detailed anatomy of intracranial structures has been studied mainly
in cadavers, but the absence of cerebrospinal fluid and blood pressure in these
models distorts normal spatial relationships. The authors investigated the
rotation of the facial nerve (FN), superior vestibular nerve (SVN), inferior
vestibular nerve (IVN), and cochlear nerve (CN) in the internal auditory canal
(IAC) and cerebellopontine cistern in human volunteers and compared their results
with those reported in cadaver studies. METHODS: The IACs and cerebellopontine
cisterns of 30 normal adults (34 sides) were examined using magnetic resonance
(MR) cisternography with a heavily T2-weighted two-dimensional fast spin-echo
technique. The positions of the four components were unaffected by the presence
of the meatal loop of the anterior inferior cerebellar artery in the IAC. The
spatial relationship between the FN and SVN was quite constant, but the spatial
relationship between the CN and SVN was quite variable: the former changed
position, mainly in the IAC, on nine (26.5%) of 34 sides, and in the
cerebellopontine cistern on the other sides (73.5%), conflicting with findings in
cadaver studies. CONCLUSIONS: It is more accurate to describe the CN and IVN as
coursing beneath the SVN in either the IAC or cerebellopontine cistern, rather
than stating that the three components rotate, as reported in cadaver studies.
The MR cisternography studies provided quite detailed information about the
topography of the four components and the relationship between the blood vessels
and cranial nerves in the IAC and the cerebellopontine cistern.
PMID- 10193606
TI - The acute period of recovery from traumatic brain injury: posttraumatic amnesia
or posttraumatic confusional state?
AB - OBJECT: The goal of this study was to characterize more fully the cognitive
changes that occur during the period of acute recovery after traumatic brain
injury (TBI). METHODS: The pattern of performance recovery on attention and
memory tests was compared with the results of the Galveston Orientation and
Amnesia Test (GOAT). Tests of memory and attention were administered serially to
a hospitalized group of patients with TBI of varying severity. The tests differed
in their level of complexity and/or requirement for more effortful or strategic
processing. The authors found a regular pattern to recovery. As expected, ability
to perform on simpler tests was recovered before performance on more effortful
ones. The ability to recall three words freely after a 24-hour delay (the
operational definition in this study of return to continuous memory) was
recovered last, later than normal performance on the GOAT. Ability to perform
simple attentional tasks was recovered before the less demanding memory task
(recognition); ability to perform more complex attentional tasks was recovered
before the free recall of three words after a 24-hour delay. This recovery of
attention before memory was most notable and distinct in the group with mild TBI.
CONCLUSIONS: The period of recovery after TBI, which is currently termed
posttraumatic amnesia, appears to be primarily a confusional state and should be
labeled as such. The authors propose a new definition for this acute recovery
period and argue that the term posttraumatic confusional state should be used,
because it more appropriately and completely characterizes the early period of
recovery after TBI.
PMID- 10193607
TI - The ciliospinal reflex in pentobarbital coma.
AB - OBJECT: This study was conducted to delineate the ciliospinal reflex (CSR), which
is defined as pupillary dilation caused by a noxious stimulus to the face or
head. The authors anecdotally observed that patients in a pentobarbital coma have
a CSR that can mimic pathological conditions. A pentobarbital coma obscures the
results of the neurological examination in patients with potentially life
threatening cerebral edema; pupil size and reactivity are the only readily
monitored signs. Any condition that incorrectly suggests evolving intracranial
pathological processes can lead to unnecessary clinical actions. METHODS: The
authors evaluated six consecutive patients in the neurointensive care unit in
whom a pentobarbital coma had been induced, documenting the presence and duration
of the CSR. The CSR was always bilateral and symmetrical, manifesting as enlarged
(6-8 mm), seemingly nonreactive pupils continuing from 1 to 6 minutes and was
usually seen after routine nursing maneuvers. The pupils appeared nonreactive to
short flashes of direct light but did react if longer flashes were used.
CONCLUSIONS: Recognition of the CSR can potentially lead to reduction of
unnecessary transportation and complicating medical interventions in critically
neurologically ill patients in whom a pentobarbital coma has been induced.
PMID- 10193608
TI - Differential effects of octreotide treatment and transsphenoidal surgery on
growth hormone-binding protein levels in patients with acromegaly.
AB - OBJECT: The high-affinity growth hormone-binding protein (GHBP) represents the
extracellular portion of the growth hormone (GH) receptor, and its serum levels
are a reflection of the tissue receptor status. Levels of GHBP are decreased in
patients with active acromegaly, probably because of downregulation of GH
receptors. However, there are no studies of patients with acromegaly in which the
effects of medical (that is, administration of somatostatin analogs) and surgical
therapy on GHBP levels have been compared. That is the task the authors set out
to accomplish in this study. METHODS: The authors studied seven patients in whom
acromegaly had been recently diagnosed. They examined these patients at baseline,
2 months after octreotide treatment (subcutaneous administration of 100 microg
octreotide three times per day), and 1 month after transsphenoidal surgery.
Growth hormone-binding activity was measured, as well as the following
biochemical markers of the somatotropic axis: GH suppression induced by oral
administration of glucose, insulin-like growth factor-I (IGF-I), and insulin-like
growth factor-binding protein-3 (IGFBP3). Although octreotide treatment induced a
decrease in the levels of GH, IGF-I, and IGFBP3, as well as an increase in the
level of GHBP, these biochemical markers did not reach normal levels. On the
other hand, after transsphenoidal surgery, GHBP levels became normal,
particularly in those patients in whom serum GH could be suppressed to an
undetectable level after glucose loading. CONCLUSIONS: The authors conclude that
persistently low GHBP levels in patients with acromegaly are normalized by
successful pituitary surgery and correlate well with disease activity.
PMID- 10193609
TI - Use of the radial forearm microvascular free-flap graft for cranial base
reconstruction.
AB - OBJECT: Reconstruction of the cranial base after resection of complex lesions
requires creation of both a vascularized barrier to cerebrospinal fluid (CSF)
leakage and tailored filling of operative defects. The authors describe the use
of radial forearm microvascular free-flap grafts to reconstruct skull base
lesions, to fill small tissue defects, and to provide an excellent barrier
against CSF leakage. METHODS: Ten patients underwent 11 skull base procedures
including placement of microvascular free-flap grafts harvested from the forearm
and featuring the radial artery and its accompanying venae comitantes. Operations
included six craniofacial, three lateral skull base, and two transoral procedures
for various diseases. Excellent results were obtained, with no persistent CSF
leaks, no flap failures, and no operative infections. One temporary CSF leak was
easily repaired with flap repositioning, and at one flap donor site minor wound
breakdown was observed. One patient underwent a second procedure for tumor
recurrence and CSF leakage at a site distant from the original operation.
CONCLUSIONS: Microvascular free tissue transfer reconstruction of skull base
defects by using the radial forearm flap provides a safe, reliable, low-morbidity
method for reconstructing the skull base and is ideally suited to "low-volume"
defects.
PMID- 10193610
TI - Five-year experience in using coil embolization for ruptured intracranial
aneurysms: outcomes and incidence of late rebleeding.
AB - OBJECT: During a 5-year period 317 patients presenting with aneurysmal
subarachnoid hemorrhage were successfully treated by coil embolization within 30
days of hemorrhage. The authors followed patients to assess the stability of
aneurysm occlusion and its longer-term efficacy in protecting patients against
rebleeding. METHODS: Patients were followed for 6 to 65 months (median 22.3
months) by clinical review, angiography performed at 6 months posttreatment, and
annual questionnaires. Stable angiographic occlusion was evident in 86.4% of
small and 85.2% of large aneurysms with recurrent filling in 38 (14.7%) of 259
aneurysms. Rebleeding was caused by aneurysm recurrence in four patients (between
11 and 35 months posttreatment) and by rupture of a coincidental untreated
aneurysm in one patient. Annual rebleeding rates were 0.8% in the 1st year, 0.6%
in the 2nd year, and 2.4% in the 3rd year after aneurysm embolization, with no
rebleeding in subsequent years. Rebleeding occurred in three (7.9%) of 38
recurrent aneurysms and in one (0.4%) of 221 aneurysms that appeared stable on
angiography. CONCLUSIONS: Periodic follow-up angiography after coil embolization
is recommended to identify aneurysm recurrence and those patients at a high risk
of late rebleeding.
PMID- 10193611
TI - Improved survival after aneurysmal subarachnoid hemorrhage: review of case
management during a 12-year period.
AB - OBJECT: Based on the concept that unfavorable clinical outcome after aneurysmal
subarachnoid hemorrhage (SAH), to a large extent, is a consequence of all
ischemic insults sustained by the brain during the acute phase of the disease,
management of patients with SAH changed at the authors' institution in the mid
1980s. The new management principles affected referral guidelines, diagnostic and
monitoring methods, and pharmacological and surgical treatment in a
neurointensive care setting. The impact of such changes on the outcome of
aneurysmal SAH over a longer period of time has not previously been studied in
detail. This was the present undertaking. METHODS: The authors analyzed all
patients with SAH admitted to the neurosurgery department between 1981 and 1992.
This period was divided in two parts, Period A (1981-1986) and Period B (1987
1992), and different aspects of management and outcome were recorded for each
period. In total, 1206 patients with SAH (mean age 52 years, 59% females) were
admitted; an aneurysm presumably causing the SAH was found in 874 (72%). The 30
day mortality rate decreased from 29% during the first 2 years (1981-1982) to 9%
during the last 2 years (1991-1992) (Period A 22%; Period B 10%; p<0.0001) and
the 6-month mortality rate decreased from 34 to 15% (Period A 26%; Period B 16%;
p<0.001). At follow-up review conducted 2 to 9 years (mean 5.2 years) after SAH
occurred, patients were evaluated according to the Glasgow Outcome Scale.
Subarachnoid hemorrhage-related poor outcome (vegetative or dead) was reduced
(Period A 30%; Period B 18%; p<0.001). There was an increase both in patients
with favorable outcome (good recovery and moderate disability) (Period A 61 %;
Period B 66%) and in those with severe disability (Period A 9%; Period B 16%;
p<0.01). CONCLUSIONS: This study provides evidence that the prognosis for
patients with aneurysmal SAH has improved during the last decades. The most
striking results were a gradual reduction in mortality rates and improved
clinical outcomes in patients with Hunt and Hess Grade I or II SAH and in those
with intraventricular hemorrhage. The changes in mortality rates and the clinical
outcomes of patients with Hunt and Hess Grades III to V SAH were less
conspicuous, although reduced incidences of mortality were seen in some
subgroups; however, few survivors subsequently appeared to attain a favorable
outcome.
PMID- 10193612
TI - A simple relationship between radiological arteriovenous malformation
hemodynamics and clinical presentation: a prospective, blinded analysis of 31
cases.
AB - OBJECT: The authors sought to establish prospectively whether there is a simple
relationship between radiological features of brain arteriovenous malformation
(AVM) hemodynamics and a patient's clinical presentation. METHODS: Thirty-one
consecutive patients with AVMs underwent cerebral angiography at 3.8
frames/second during each standardized injection of contrast material. Contrast
dilution curves were derived from the image sequences by using regions of
interest (ROIs) traced on arteries feeding and veins draining the AVM nidus.
Angiographic parameters were then analyzed in a blinded fashion. These parameters
included the times required to reach the peak contrast density, the contrast
decay time, and fractions thereof, in the ROI for each vessel. The authors
determined whether these parameters, the arteriovenous transit time, and/or AVM
size were related to patients' presentation with hemorrhage (11 patients),
seizure (11 patients), or other clinical symptoms (nine patients). Statistically
significant results were found only in analyses of arterial phase times to reach
peak contrast density. Analyses of venous parameters, AVM size, and nidus transit
time showed trends but no statistical significance. Arterial filling with
contrast material was significantly slower in patients presenting with hemorrhage
(mean 50%, 80%, and 100% of time to peak +/- standard error [SE] = 1.19+/-0.13,
1.97+/-0.18, and 3.04+/-0.34 seconds, respectively) compared with patients
presenting with seizures (mean 50%, 80%, and 100% of time to peak +/- SE = 0.80+/
0.12, 1.32+/-0.18, and 1.95+/-0.29 seconds, respectively) according to analysis
of variance (p<0.05) and post-hoc t-tests (p<0.05) for each parameter. Patients
who presented with other symptoms had intermediate arterial filling times.
CONCLUSIONS: These simple hemodynamic parameters, which can be obtained without
added risk to the patient, may help identify a subset of individuals in whom AVMs
pose a higher risk of future hemorrhage and who may therefore warrant more
expeditious treatment.
PMID- 10193613
TI - How should a subarachnoid hemorrhage grading scale be determined? A combinatorial
approach based solely on the Glasgow Coma Scale.
AB - OBJECT: The purpose of this study was to present a combinatorial approach used to
develop a subarachnoid hemorrhage (SAH) grading scale based on the patient's
preoperative Glasgow Coma Scale (GCS) score. METHODS: There are 4094 different
combinations that can be used to compress the 13 scores of the GCS into two to 12
grades. Break points, the positions in the scale in which two adjacent scores
connote a significantly different outcome, are obtained by a direct comparison of
the GCS and the Glasgow Outcome Scale (GOS). Guided by the break points, the
number of combinations to be considered can be limited. All possible combinations
are statistically analyzed with respect to intergrade differences in outcome.
Single combinations, with the maximum number of grades having maximum intergrade
outcome differences for each corresponding set of adjacent grades, must be
selected. The authors verified the validity of this combinatorial approach by
retrospectively analyzing 1398 consecutive patients with aneurysmal SAH who
underwent surgery within 7 days of the last hemorrhage episode. The patients' GCS
scores were assessed just before surgery and their GOS scores were estimated 6
months post-SAH. The combinatorial approach yields only one acceptable grading
scale: I (GCS Score 15); II (GCS Scores 11-14); III (GCS Scores 8-10); IV (GCS
Scores 4-7); and V (GCS Score 3). CONCLUSIONS: The combinatorial approach, guided
by the break points, is so simple and systematic that it can be used again in the
future when revision of the grading scale becomes necessary after development of
new and effective treatment modalities that improve patients' overall outcome.
PMID- 10193614
TI - Percutaneous transluminal angioplasty and stent placement for recurrent carotid
artery stenosis.
AB - OBJECT: Treatment consisting of percutaneous transluminal angioplasty (PTA) and
stent placement has recently been proposed as an alternative to surgical
reexploration in patients with recurrent carotid artery stenosis following
endarterectomy. The authors retrospectively reviewed their experience after
performing 25 procedures in 21 patients to assess the safety and efficacy of PTA
with or without stent placement for carotid artery restenosis. METHODS: The mean
interval between endarterectomy and the endovascular procedures was 57 months
(range 8-220 months). Seven arteries in five patients were treated by PTA alone
(including bilateral procedures in one patient and repeated angioplasty in the
same vessel in another). Early suboptimum results and recurrent stenosis in some
of these initial cases prompted the authors to combine PTA with stent placement
in the treatment of 18 arteries over the past 3 years. No major periprocedural
deficits (neurological or cardiac complications) or death occurred. There was one
periprocedural transient neurological event, and in one patient a pseudoaneurysm
of the femoral artery (at the access site) required surgical repair. In the 16
patients who each underwent at least 6 months of follow-up review, no
neurological events ipsilateral to the treated artery had occurred after a mean
follow-up period of 27 months (range 6-57 months). Three of five patients who
underwent PTA alone developed significant (>50%) asymptomatic restenoses that
required repeated angioplasty in one and PTA with stent placement in two
patients. Significant restenosis (55%) was observed in only one of the vessels
treated by combined angioplasty and stent placement. CONCLUSIONS: Endovascular
PTA and stenting of recurrent carotid artery stenosis is both technically
feasible and safe and has a satisfactory midterm patency. This procedure can be
considered a viable alternative to surgical reexploration in patients with
recurrent carotid artery stenosis.
PMID- 10193615
TI - Delayed neurological deterioration following resection of arteriovenous
malformations of the brain.
AB - OBJECT: The aim of this study was to analyze delayed neurological deficits
following surgical resection of arteriovenous malformations (AVMs). METHODS: The
authors report on a consecutive series of 200 patients with angiographically
proven AVMs of the brain that were surgically resected between January 1989 and
June 1998. The 30-day mortality rate for patients in this series was 1%, with one
death caused by AVM resection and one death attributed to basilar artery aneurysm
repair following successful AVM resection. The Spetzler-Martin grading system
correlated well with the difficulty of surgery. No permanent incidence of
morbidity resulted from resection of Grade I or II AVMs; the percentage of
patients with a significant neurological deficit due to resection was 7.8% for
those with Grade III lesions and 33.3% for those with Grade IV or V AVMs.
However, this grading system did not accurately predict the development of
delayed neurological deficits. Ten patients (5%) developed delayed neurological
deficits after recovering from anesthesia and surgery. The delayed deficit was
due to hemorrhage in four of the 10 patients and all four had undergone resection
of AVMs measuring at least 4 cm in diameter. An increase in blood pressure during
the first 8 postoperative days precipitated hemorrhage in these patients. Edema
arising as a consequence of propagated venous thrombosis (two patients) was
associated with extensive venous drainage networks rather than large AVM niduses.
Both hemorrhagic and edematous complications can be included under the umbrella
term of "arterial-capillary-venous hypertensive syndrome" to describe the common
underlying pathogenesis accurately. An additional four patients developed a
delayed deficit as a result of vasospasm. Vasospasm occurred when resection had
involved extensive dissection of proximal anterior and middle cerebral arteries;
in such cases the incidence of vasospasm was 27%. CONCLUSIONS: On the basis of
their analysis of these complications, the authors recommend strict blood
pressure control for patients with lesions measuring 4 cm or more in diameter
(particularly those with a deep arterial supply). Thromboprophylaxis with aspirin
and heparin is prescribed for patients with extensive venous drainage networks,
and prophylactic nimodipine therapy and angiographic surveillance for vasospasm
are suggested for patients in whom extensive dissection of proximal anterior or
middle cerebral arteries has been necessary.
PMID- 10193616
TI - Efficacy of induced hypotension in the surgical treatment of large cavernous
sinus cavernomas.
AB - OBJECT: Cavernous sinus cavernomas are rare lesions associated with high rates of
intraoperative mortality and morbidity resulting from profuse bleeding. In this
paper, the authors report their experience in treating five patients with
histologically confirmed cavernous sinus cavernomas and describe the efficacy of
induced hypotension in facilitating excision of the lesion. METHODS: All five
patients were women ranging in age from 25 to 54 years, with an average age of 42
years. The mass was small in one and large (>3 cm in diameter) in four. In one
patient with a large mass, cardiac arrest occurred after the craniotomy, and
remarkable reduction in the size of the cavernoma was evident on postmortem
examination. The other three large lesions were successfully removed piecemeal
after induction of hypotension (60-80 mm Hg systolic pressure), which remarkably
reduced the mass and the bleeding during surgery. In the remaining patient, who
had a small lesion, the cavernoma was removed in one piece. CONCLUSIONS:
Cavernous sinus cavernoma can be thought of as a cluster of sinusoidal cavities,
the size of which varies depending on the systemic blood pressure. During
surgery, reduction of the mass and control of bleeding from the cavernoma can be
achieved by inducing hypotension, which enables the safe excision of this lesion.
This technique should be considered by surgeons resecting a cavernous sinus
tumor, especially when cavernoma is suspected.
PMID- 10193617
TI - Theoretical comparison of surgery and radiosurgery in cerebral arteriovenous
malformations.
AB - OBJECT: Management of patients with cerebral arteriovenous malformations (AVMs)
is controversial. Excellent surgical results are obtained in patients with low
Spetzler-Martin grades, whereas radiosurgery offers a good alternative with its
high obliteration rate. In the absence of randomized studies, physicians must
choose a treatment plan based on the currently available data. To support this
decision-making process, a mathematical model designed to describe patient
survival rates after each treatment option was developed. METHODS: The
theoretical survival curve in patients undergoing conventional surgery,
radiosurgery, or observation was calculated. Theoretical life expectancies in
patients with AVMs who presented at various initial ages were calculated for each
treatment strategy. A systematic method was also developed to compare the
estimated risks of various treatment combinations. CONCLUSIONS: Conventional
surgery and radiosurgery definitely produced better survival rates than
observation. In the comparison of surgery with radiosurgery, radiosurgery was
equivalent to surgery with a combined morbidity and mortality rate of
approximately 7% for a 20-year-old patient with an unruptured cerebral AVM. Data
for other patient ages and treatment combinations are tabulated for use in
determining the best treatment strategy. The authors believe that their analysis
will provide logical support for the decision-making process involved in the
treatment of patients with cerebral AVMs.
PMID- 10193618
TI - Topographic anatomy of the insular region.
AB - OBJECT: The insula is one of the paralimbic structures and constitutes the
invaginated portion of the cerebral cortex, forming the base of the sylvian
fissure. The authors provide a detailed anatomical study of the insular region to
assist in the process of conceptualizing a reliable surgical approach to allow
for a successful course of surgery. METHODS: The topographic anatomy of the
insular region was studied in 25 formalin-fixed brain specimens (50 hemispheres).
The periinsular sulci (anterior, superior, and inferior) define the limits of the
frontoorbital, frontoparietal, and temporal opercula, respectively. The opercula
cover and enclose the insula. The limen insula is located in the depths of the
sylvian fissure and constitutes the anterobasal portion of the insula. A central
insular sulcus divides the insula into two portions, the anterior insula (larger)
and the posterior insula (smaller). The anterior insula is composed of three
principal short insular gyri (anterior, middle, and posterior) as well as the
accessory and transverse insular gyri. All five gyri converge at the insular
apex, which represents the most superficial aspect of the insula. The posterior
insula is composed of the anterior and posterior long insular gyri and the
postcentral insular sulcus, which separates them. The anterior insula was found
to be connected exclusively to the frontal lobe, whereas the posterior insula was
connected to both the parietal and temporal lobes. Opercular gyri and sulci were
observed to interdigitate within the opercula and to interdigitate the gyri and
sulci of the insula. Using the fiber dissection technique, various unique
anatomical features and relationships of the insula were determined. CONCLUSIONS:
The topographic anatomy of the insular region is described in this article, and a
practical terminology for gyral and sulcal patterns of surgical significance is
presented. This study clarifies and supplements the information presently
available to help develop a more coherent surgical concept.
PMID- 10193619
TI - Scanning electron microscopy of the floor of the fourth ventricle in rats
subjected to graded impact injury to the sensorimotor cortex.
AB - OBJECT: Respiratory dysfunction including apnea frequently follows head injury in
humans. The purpose of this study was to identify any structural alterations in
the region of brainstem respiratory nuclei that might account for immediate
postinjury respiratory abnormalities in anesthetized experimental animals.
METHODS: Using scanning electron microscopy, the authors examined the floor of
the fourth ventricle in injured rats after a piston strike to the sensorimotor
cortex that depressed the dura 1, 2, or 4 mm. The rats were killed within minutes
of injury. Cortical impact depths measuring either 1 or 2 mm (eight rats)
produced no respiratory abnormalities, and the structural integrity of the
ependymal lining of the ventricular floor in these animals was not compromised.
Thirteen rats were subjected to impact to a 4-mm depth and 10 of these exhibited
immediate temporary or permanent apnea. The medullae of nine of these rats were
studied using scanning electron microscopy, and the fourth ventricular floors of
all nine rats showed tears. Four rats that exhibited immediate, permanent apnea
had tears in the caudal fourth ventricle floor near the obex, whereas five rats
with no or only transient apnea had tears located more anteriorly, near the
aqueduct or laterally. Changes in cerebrospinal fluid flow or pressure dynamics
may have caused these tears. Light microscopy, focused near the area postrema,
revealed a shearing defect through the ependyma of the fourth ventricular floor
into the subjacent neuropil with a disruption of axonal pathways. CONCLUSIONS:
Respiratory neuronal network components lying within 2 mm of the area postrema
may well have been disrupted by the caudal tears producing permanent apnea. A
similar phenomenon could account for the transient or permanent postinjury apnea
seen in humans with severe head injury.
PMID- 10193620
TI - Role of protein tyrosine phosphorylation in erythrocyte lysate-induced
intracellular free calcium concentration elevation in cerebral smooth-muscle
cells.
AB - OBJECT: Tyrosine kinases play an important role in the regulation of systemic
vascular smooth-muscle tone. The authors studied the involvement of protein
tyrosine kinase activity in erythrocyte lysate-mediated signal transduction in
cerebral smooth-muscle cells. METHODS: Tyrosine kinase phosphorylation and
intracellular free Ca++ ([Ca++]i) were measured in rat aortic and basilar artery
smooth-muscle cells by using Western blot and fura 2-acetoxymethyl ester
microfluorimetry. Erythrocyte lysate enhanced tyrosine phosphorylation in
cultured rat aortic and basilar smooth-muscle cells and induced a rapid transient
and a prolonged plateau phase of [Ca++]i response in rat basilar smooth-muscle
cells. The tyrosine kinase inhibitors genistein and tyrphostin A51 (administered
at concentrations of 30 or 100 microM) attenuated both phases of erythrocyte
lysate-induced [Ca++]i elevation. Erythrocyte lysate was separated into low- (<10
kD, which contains adenine nucleotides) and high- (>10 kD, which contains
hemoglobin) molecular-weight fractions; these fractions were tested separately in
these cells. The low-molecular-weight fraction produced a similar [Ca++]i
response to that of erythrocyte lysate and the high-molecular-weight fraction
produced a small response. The [Ca++]i responses from both fractions were
inhibited by tyrosine kinase inhibitors. CONCLUSIONS: To the authors' knowledge,
this is the first report to show that tyrosine phosphorylation may be involved in
erythrocyte lysate-induced signal transduction and [Ca++]i responses in cerebral
smooth-muscle cells.
PMID- 10193621
TI - Vascular components of cerebrospinal fluid compensation.
AB - OBJECT: The aim of the study was to assess how cerebrospinal fluid (CSF) pressure
volume compensation depends on cerebrovascular tone. METHODS: In 26 New Zealand
White rabbits, intracranial pressure (ICP), arterial blood pressure, and basilar
artery blood flow velocity were measured continuously. Saline was infused into
the cranial subarachnoid space to assess CSF compensatory parameters: the
resistance to CSF outflow, the elastance coefficient, and the amplitude of the
ICP pulsatile waveform. Infusions were repeated on two different levels of CO2
concentration in the arterial blood (PaCO2), at normotension and hypotension, and
after the death of the animal. An increase in PaCO2 from a mean of 27 to 48 mm Hg
was accompanied by an 18% increase in the resistance to CSF outflow (p<0.005) and
a 64% increase (p<0.05) in the elastance coefficient. A decrease in arterial
blood pressure from a mean of 100 to 51 mm Hg caused a 25% decrease in CSF
outflow resistance (p<0.01) but did not affect the elastance coefficient.
Postmortem, a 23% decrease in the CSF outflow resistance was associated with a
102% decrease in the elastance coefficient. CONCLUSIONS: Cerebrovascular
parameters have a limited but significant impact on CSF infusion studies. The
vascular component of ICP may be identified as a significant factor contributing
to this phenomenon. During infusion studies, physiological parameters influencing
vascular conditions should be maintained as stable as possible.
PMID- 10193622
TI - Nimodipine-induced improved survival rate of facial motor neurons following
intracranial transection of the facial nerve in the adult rat.
AB - OBJECT: Neuronal survival is an important factor in the achievement of functional
restitution after peripheral nerve injuries. Intracranial tumors or trauma may
cause patients to exhibit a temporary or permanent facial nerve palsy.
Nimodipine, which acts as an antagonist to L-type voltage-gated calcium channels,
has been shown to be neuroprotective in various lesion models of the central and
peripheral nervous systems. The aim of the present study was to evaluate the
effect of nimodipine on motor neuron survival in the facial motor nucleus
following intracranial transection of the adult rat facial nerve. METHODS: The
facial nerve was cut intracranially in the posterior cranial fossa. Nimodipine
was administered orally preoperatively for 3 days and postoperatively for up to 1
month, after which the number of neuronal profiles was quantified. The glial
reaction was studied in the facial nucleus for up to 1 month by using
immunocytochemical analysis. There was a significantly larger proportion of
surviving motor neurons 1 month postinjury in animals treated with nimodipine
(61+/-6.7%) in comparison with untreated animals (26.8+/-11.3%).
Immunocytochemical analysis showed an increase in the amount of OX42 (microglia),
ED1 (macrophages), and anti-glial fibrillary acidic protein (astrocytes)
ipsilateral to the nerve injury; however, there was no difference between the two
experimental groups of animals 2 to 28 days after surgery. CONCLUSIONS: The
authors propose a neuroprotective role for nimodipine, which may be useful as a
"cranial nerve protective agent" following insults such as head injury or skull
base surgery.
PMID- 10193623
TI - Complex right hemisphere developmental venous anomaly associated with multiple
facial hemangiomas. Case report.
AB - Complex developmental venous anomalies (DVAs) represent variations of normal
cerebral venous drainage and consist of dilation of the superficial and/or deep
venous system. These rare anomalies can occur unilaterally or bilaterally,
supratentorially or infratentorially, focally or they can affect the entire
hemisphere. Some DVAs are associated with cervicofacial venous malformations or
facial lymphatic malformations. Anomalies of this type are generally clinically
silent, and cerebral dysfunction is usually absent. Symptoms, when they occur,
are most commonly headache or mild seizure disorders. The angiographic findings
are striking, with well-formed but enlarged transcerebral medullary and deep
and/or superficial cortical veins. Opacification of these venous structures
occurs within the same time frame as a normal angiographic venous phase. The
authors report the case of a 33-year-old man in whom a large inoperable
arteriovenous malformation had been previously diagnosed and who presented with
seizures. Repeated magnetic resonance imaging and angiography demonstrated
abnormally dilated transcerebral, superficial, and deep venous structures
involving the entire right hemisphere with no identifiable nidus. Additionally,
multiple bilateral benign facial hemangiomas were present in this patient. It is
important to recognize this rare venous appearance as a developmental variant and
not mistake it for an arteriovenous malformation or a partially thrombosed vein
of Galen malformation. Because these venous anomalies are extreme variants of the
normal venous system, hemorrhage rarely, if ever, occurs and the patient can be
reassured that no interventional or surgical therapy is necessary or warranted.
PMID- 10193624
TI - Cerebral heterotopia of the temporofacial region. Case report.
AB - The authors report a case of cerebral heterotopia in the right temporofacial
region of a neonate. The lesion presented as a massive cystic swelling containing
cerebrospinal fluid. It produced calvarial and facial bone deformities. After the
mass was excised, histological examination revealed glial tissue and choroid
plexus.
PMID- 10193625
TI - Persistent bilateral hearing loss after shunt placement for hydrocephalus. Case
report.
AB - Transient hearing decrease following loss of cerebrospinal fluid (CSF) has been
reported in patients undergoing lumbar puncture, spinal anesthesia, myelography,
and/or different neurosurgical interventions. The authors present the first well
documented case of a patient with persistent bilateral low-frequency
sensorineural hearing loss after shunt placement for hydrocephalus and discuss
the possible pathophysiological mechanisms including the role of the cochlear
aqueduct. These findings challenge the opinion that hearing decreases after loss
of CSF are always transient. The authors provide a suggestion for treatment.
PMID- 10193626
TI - Lhermitte-Duclos disease as a component of Cowden's syndrome. Case report and
review of the literature.
AB - In recent years, 16 cases involving the association between Lhermitte-Duclos
disease (LDD), which is a hamartomatous overgrowth of cerebellar tissue, and
Cowden's syndrome (CS), an autosomal-dominant condition characterized by multiple
hamartomas and neoplasias, have been reported. LDD may be one of the
manifestations of CS. Recently, mutations of the PTEN/MMAC 1 gene, a tumor
suppressor gene, have been found in families with CS, including four patients in
whom LDD was diagnosed. The authors present a case of LDD in a 53-year-old woman
who also had the typical mucocutaneous lesions found in CS, as well as goiter and
intestinal polyposis. In this case, CS had never been suspected until the
diagnosis of LDD was made. The mutation detected in the PTEN/MMAC 1 gene as well
as neuropathological results are described.
PMID- 10193627
TI - Computer-generated surgical simulation of morphological changes in
microstructures: concepts of "virtual retractor." Technical note.
AB - The authors' goal was to develop a computer graphics model to simulate the
displacement and morphological changes that are caused by the retraction of fine
intracranial structures. The authors developed an application program to
interpolate the contour of models of an artery and a retractor. The center of the
displacement was determined by spatial coordinates, and the shape of the
displacement of the arterial model was calculated using a cosine-based formula
with representation of a brain retractor. This computer graphics model was
applied to the simulation of the displacement and morphological changes that
occur when retraction is performed in the optic nerve. An illustrative case is
presented, in which the optic nerve was displaced by a retractor to simulate the
surgery performed in a carotid cave aneurysm of the internal carotid artery. The
authors have named this methodological tool a "virtual retractor." This new
navigational system for open microneurosurgery would be useful in teaching
surgical microanatomy and in presurgical operative planning.
PMID- 10193628
TI - Long-term patency of radial artery graft bypass for reconstruction of the
internal carotid artery. Technical note.
AB - Reconstruction of the carotid artery by using a radial artery graft is a useful
option that can produce reliable long-term patency for the surgical treatment of
giant and/or large aneurysms of the cavernous and paraclinoid internal carotid
artery (ICA). During the past 10 years, 43 patients with intracavernous and
paraclinoid giant aneurysms of the ICA have been treated by reconstruction of the
ICA with radial artery grafts after ligation of the cervical ICA. The long-term
patency of the grafted radial artery was evaluated over more than a 5-year period
(mean 7.2 years) in 20 of these patients by using magnetic resonance angiography
or conventional angiography. There was no late occlusion of the graft in any of
these cases. Stenotic graft changes were observed in two cases.
PMID- 10193630
TI - Postoperative ectopic seeding of craniopharyngioma. Case illustration.
PMID- 10193629
TI - Clinical application of three-dimensional anisotropy contrast magnetic resonance
axonography. Technical note.
AB - The utility of three-dimensional anisotropy contrast (3DAC) magnetic resonance
(MR) axonography, a method sensitive to neuronal fibers and their directionality,
was investigated in the clinical setting using a 3-tesla MR imaging system based
on a General Electric Signa platform. The study focused on healthy volunteers and
patients with common structural central nervous system disorders, namely chronic
infarction, brainstem cavernous hemangioma, supratentorial meningioma, and
astrocytoma. Three orthogonal anisotropic diffusion-weighted images were first
obtained. Three primary colors were each assigned to a diffusion-weighted image,
respectively, and the images were subsequently combined into a single-color image
in full-color spectrum (3DAC MR axonography image). Fiber-tract definition in the
cerebral peduncle of the midbrain of healthy volunteers showed intersubject
variation, with two general patterns recognized: dispersed (60% of cases) and
compact (40% of cases). Pathological alterations in the fiber tracts were readily
identified in cases involving wallerian degeneration of the pyramidal tract, as
illustrated in the cases of chronic infarction. Displacement of major tracts,
such as the medial lemniscus or corticospinal tract, as well as fiber
directionality, was also easily recognized in cases of mass lesions. As an
imaging method uniquely capable of providing information regarding axonal
connectivity, 3DAC MR axonography appears to have promising potential for routine
clinical application.
PMID- 10193631
TI - Charles George Drake, M.D. 1920-1998.
PMID- 10193632
TI - Disc pathology.
PMID- 10193633
TI - Graft survival.
PMID- 10193634
TI - Sciatic nerve injury.
PMID- 10193635
TI - Search for the soul.
PMID- 10193636
TI - Delayed aneurysm regrowth.
PMID- 10193637
TI - Surgery for acromegaly.
PMID- 10193638
TI - MIB-1 and Schwannomas.
PMID- 10193639
TI - Leukocyte recovery from umbilical cord blood by poligeline.
AB - Umbilical cord blood (UCB) collected at delivery is a source of transplantable
stem/progenitor cells; it represents an alternative to bone marrow to restore
hematopoiesis in patients affected by malignant and non-malignant disease.
Therefore, large-scale UCB banks would be a natural complement to bone marrow
donor registries. Storage of unmanipulated whole UCB units requires a great
number of liquid nitrogen containers. Separation of leukocytes allows UCB storage
in smaller space, thus lowering banking costs; unfortunately, UCB processing may
cause significant losses of stem cells. We report about the use of poligeline to
remove erythrocytes from UCB units. After erythrocyte sedimentation at 1xg (30'
or 40') or 50xg, leukocyte-rich supernatant was collected and centrifuged to
recover the leukocyte pool in view of stem cell transplantation. Erythrocyte
depletion was always satisfactory, ranging from 82.6% to 88.9%, but 1xg
sedimentation for 40' enabled us to achieve the best CD34+ cell recovery (mean
value 80.5%). The proposed UCB-processing method allowed us to lower the final
sample volume down to 1/10 of the initial one, in this way making UCB banking
feasible. Erythrocyte depletion took place directly in the collection bag, thus
reducing microbial contamination risk.
PMID- 10193640
TI - Positive selection of CD34+ peripheral blood progenitor cells in patients with
low-grade lymphoid malignancies and bone marrow involvement.
AB - PURPOSE: 16 patients with low-grade lymphoid malignancies and bone marrow
involvement were transplanted with selected CD34 positive Peripheral Blood
Progenitor Cell (PBSC) prepared from autologous aphereses. PATIENT AND METHODS:
All but one patients were mobilized with a combination of chemotherapy (including
high-dose cyclophosphamide and VP16 or adriamycin, aracytin with cysplatyl) and
recombinant human Granulocyte Colony-Stimulating Factor (rhG-CSF). RESULTS: A
median of 3 (range, 1 to 9) aphereses yielded 15.35 x 10(6) CD34+ cells/kg
(range, 4.45 to 70.88). A median of 5.01 x 10(6) adsorbed CD34+ cells/kg (range
2.01 to 24.13) was obtained after selection (median purity: 86%; range, 59-99%).
The CD34 PBSC were infused one day after either one of two conditioning regimens:
11 patients received the association of cyclophosphamide (120 mg/kg) and TBI
(8Gy), and 5 patients received the BEAM regimen. No recombinant hematopoietic
growth factor was used after cell reinfusion. Median days to 0.5 x 10(9)/l
neutrophils and 50 x 10(9)/l platelets were 13 (range, 9 to 18) and 16 (range, 11
to 35), respectively. The median number of red blood cell (RBC) unit transfusions
was 4 (range, 0 to 10). The median number of platelet transfusions was 3.5
(range, 0 to 8). No individual received backup PBSC, nor required platelet
transfusion beyond 3 months post-transplant. CONCLUSION: This study confirms the
feasability of using blood CD34 cells to support hematopoietic recovery after
myelo-suppressive or myelo-ablative regimens, in patients with low-grade NHL.
PMID- 10193641
TI - Detection of minimal residual disease in B chronic lymphocytic leukemia (CLL).
AB - In the absence of specific chromosomal translocations the best method for
detecting minimal residual disease (MRD) in B cell malignancies is based on the
uniqueness of immunoglobulin (Ig) genes rearrangement. We here report a very
sensitive method for assessing MRD in complete hematological remission (CHR)
chronic lymphocytic leukemia (CLL) patients as defined by the international
workshop on CLL (IWCLL). PATIENTS: Twelve CLL patients in CHR and complete
phenotypic remission (CPR) were included in the study. Eight of them received
Fludarabine (FDR), one was treated by Chop regimen, and the remaining 3 were
rescued by polychemotherapy followed by autologous bone marrow transplantation
(ABMT). METHODS: DNA extracted from peripheral blood lymphocytes (PBL) of each
patient was amplified with VH family specific and framework 3 primers in 5' and a
consensus JH primer in 3', before treatment and sequentially after the CPR
completion. When no clonal rearrangement could be detected by this assay, the
CDR3 sequence specific probe of the clone was used as the 3' primer, associated
to the VH family specific primer in 5'. PCR products were analyzed by classical
procedures in agarose and/or acrylamide gels. RESULTS: Mixtures of leukemic cells
and normal PBL showed detection of a single leukemic cell among more than 10(5)
normal cells. Four out of the 12 patients achieved molecular remission (MR) when
employing CDR3 amplification. All 3 autografted patients were in MR, whereas only
one out of the 9 patients treated by chemotherapy alone achieved MR. When using a
clone specific probe, a clonal signal was observed in all cases but one (ABMT).
Results presented here confirm that MR may be achieved in a few cases of B-CLL.
Further studies are needed to determine the exact relationship between MRD and
clinical outcome.
PMID- 10193642
TI - Hypermethylation of calcitonin gene in adult acute leukemia at diagnosis and
during complete remission.
AB - Hypermethylation of the calcitonin gene has been described in various hematologic
malignancies. In order to assess its frequency and potential usefulness as a
marker for leukemic cells and to detect potential clinical correlations, 180
adult patients (aged > 15 years) with newly diagnosed acute leukemia including
133 cases of acute myeloid leukemia (AML) and 47 cases of acute lymphoblastic
leukemia (ALL) were tested for its presence in leukemic blasts at diagnosis by
Southern blot technique and polymerase chain reaction (PCR) using 3 sets of
primers (P550, P566, P1400), amplifying the most frequent sites of
hypermethylation upstream or within the gene. In AML, 92 patients (69%) had
hypermethylation detected by Southern blot at diagnosis. This hypermethylation
could be confirmed by PCR in 18 of 36 tested cases (50%). Hypermethylation was
not significantly associated to any clinical or hematological characteristic of
the disease. In ALL, 44 patients (94%) had hypermethylation detected by Southern
blot at diagnosis. This hypermethylation could be confirmed by PCR in 33 of the
43 tested cases (77%). Sensitivity of PCR assessed by dilution was 1 to 0.1%.
Hypermethylation was not either significantly related to any clinical or
hematologic characteristics of the disease. Seven ALL cases which were positive
by PCR at diagnosis and achieved cytological CR could be tested during CR. Five
cases were negative and did not relapse after 3 to 27 months in CR. One case was
positive at the beginning of CR and became negative after autologous transplant.
However, he relapsed after 9 months in CR, 3 months after the last negative test.
PCR for Bcr/Abl was also negative at this time. We conclude that hypermethylation
of the calcitonine gene is frequent at diagnosis in adult acute leukemia,
particularly in ALL.
PMID- 10193643
TI - Pure red cell aplasia evolving through the hyperfibrotic myelodysplastic syndrome
to the acute myeloid leukemia: some pathogenetic aspects.
AB - The authors report a 58-year-old female who originally presented with acquired
pure red cell aplasia (PRCA). At diagnosis, the karyotype was normal, the serum
erythropoietin level was highly elevated and no T-cell mediated inhibition of
erythropoiesis was demonstrated in coculture studies. Conventional
immunosuppressive therapy proved ineffective. A year later a diagnosis of
hyperfibrotic myelodysplastic syndrome was assessed. The sequential bone marrow
examinations in the course of the three years showed a progressive increase in
bone marrow fibrosis, erythroid hyperplasia and dysmegakaryocytopoiesis,
terminating in the acute myeloid leukemia. This sequence of the events included
the appearance of del(5)(q13q33), four years after setting a diagnosis of PRCA.
The authors suggest that the absence of both cytogenetic abnormality and the
signs of dyshematopoiesis at the diagnosis of PRCA does not exclude ultimately a
"clonal" category of the disease. Thus, repeated hematological and cytogenetical
reevaluations are recommended.
PMID- 10193644
TI - Signals in stochastically generated neurons.
AB - To incorporate variation of neuron shape in neural models, we developed a method
of generating a population of realistically shaped neurons. Parameters that
characterize a neuron include soma diameters, distances to branch points, fiber
diameters, and overall dendritic tree shape and size. Experimentally measured
distributions provide a means of treating these morphological parameters as
stochastic variables in an algorithm for production of neurons. Stochastically
generated neurons shapes were used in a model of hippocampal dentate gyrus
granule cells. A large part of the variation of whole neuron input resistance
R(N) is due to variation in shape. Membrane resistivity Rm computed from R(N)
varies accordingly. Statistics of responses to synaptic activation were computed
for different dendritic shapes. Magnitude of response variation depended on
synapse location, measurement site, and attribute of response.
PMID- 10193645
TI - Emergent oscillations in a realistic network: the role of inhibition and the
effect of the spatiotemporal distribution of the input.
AB - We have simulated a network of 10,000 two-compartment cells, spatially
distributed on a two-dimensional sheet; 15% of the cells were inhibitory. The
input to the network was spatially delimited. Global oscillations frequently were
achieved with a simple set of connectivity rules. The inhibitory neurons paced
the network, whereas the excitatory neurons amplified the input, permitting
oscillations at low-input intensities. Inhibitory neurons were active over a
greater area than excitatory ones, forming a ring of inhibition. The oscillation
frequency was modulated to some extent by the input intensity, as has been shown
experimentally in the striate cortex, but predominantly by the properties of the
inhibitory neurons and their connections: the membrane and synaptic time
constants and the distribution of delays. In networks that showed oscillations
and in those that did not, widely distributed inputs could lead to the specific
recruitment of the inhibitory neurons and to near zero activity of the excitatory
cells. Hence the spatial distribution of excitatory inputs could provide a means
of selectively exciting or inhibiting a target network. Finally, neither the
presence of oscillations nor the global spike activity provided any reliable
indication of the level of excitatory output from the network.
PMID- 10193646
TI - Sodium dynamics underlying burst firing and putative mechanisms for the
regulation of the firing pattern in midbrain dopamine neurons: a computational
approach.
AB - A physiologically based multicompartmental computational model of a midbrain
dopamine (DA) neuron, calibrated using data from the literature, was developed
and used to test the hypothesis that sodium dynamics drive the generation of a
slow oscillation postulated to underlie NMDA-evoked bursting activity in a slice
preparation. The full compartmental model was reduced to three compartments and
ultimately to two variables, while retaining the biophysical interpretation of
all parameters. A phase-plane analysis then suggested two mechanisms for the
regulation of the firing pattern: (1) bursting activity is favored by
manipulations that enhance the region of negative slope in the whole-cell IV
curve and inhibited by those manipulations, such as increasing linear currents,
that tend to dampen this region and (2) assuming a region of negative slope is
present in the IV curve, the bias of the system can be altered, either enabling
or disabling bursting. The model provides a coherent framework for interpreting
the effects of glutamate, aspartate, NMDA, and GABA agonists and antagonists
under current-clamp conditions, as well as the effects of NMDA and barium under
voltage-clamp conditions.
PMID- 10193648
TI - The locomotor effects of MK801 in the nucleus accumbens of developing and adult
rats.
AB - This developmental study was an investigation of locomotion induced by the NMDA
receptor antagonist, (+)MK-801 hydrogen maleate [(5R,10S)-(+)-5-methyl-10,11
dihydro-5H-dibenzo[a,d]cyclohepten-5, 10-imine], at doses of 0, 3 or 10 microg
injected bilaterally into the nucleus accumbens of rats at 11, 21, 31, or 61-66
days of age. During a 2-h test session, only a few 11-day-old pups responded to
either dose of MK801; they displayed short bouts of obstinate progression. In
contrast, 21- and 31-day-olds were not affected by 3 microg MK801 but exhibited
robust activation after 10 microg MK801. The activation was greatest in 21-day
olds and also occurred after mid-striatal injections in 21- but not 31-day-old
rats. Adult rats injected with MK801 were not robustly activated, but they
maintained their initial level of activity throughout the test session, instead
of habituating to the test monitor, as controls did. Ontological changes in MK801
induced activity are likely to reflect maturation of glutamate transmission in
the nucleus accumbens.
PMID- 10193647
TI - Temporal sequence compression by an integrate-and-fire model of hippocampal area
CA3.
AB - Cells in the rat hippocampus fire as a function of the animal's location in
space. Thus, a rat moving through the world produces a statistically reproducible
sequence of "place cell" firings. With this perspective, spatial navigation can
be viewed as a sequence learning problem for the hippocampus. That is, learning
entails associating the relationships among a sequence of places that are
represented by a sequence of place cell firing. Recent experiments by McNaughton
and colleagues suggest the hippocampus can recall a sequence of place cell
firings at a faster rate than it was experienced. This speedup, which occurs
during slow-wave sleep, is called temporal compression. Here, we show that a
simplified model of hippocampal area CA3, based on integrate-and-fire cells and
unsupervised Hebbian learning, reproduces this temporal compression. The amount
of compression is proportional to the activity level during recall and to the
relative timespan of associativity during learning. Compression seems to arise
from an alteration of network dynamics between learning and recall. During
learning, the dynamics are paced by external input and slowed by a low overall
level of activity. During recall, however, external input is absent, and the
dynamics are controlled by intrinsic network properties. Raising the activity
level by lowering inhibition increases the rate at which the network can
transition between previously learned states and thereby produces temporal
compression. The tendency for speeding up future activations, however, is limited
by the temporal range of associations that were present during learning.
PMID- 10193649
TI - Interaction of ethanol with excitatory amino acid receptor antagonists in mice.
AB - The purpose of the present study was to determine whether the motor impairment
(myorelaxation/ataxia) induced by excitatory amino acid receptor antagonists was
exaggerated by pretreatment with ethanol. The results were compared with those of
gamma-aminobutyric acid(A) (GABA(A)) receptor positive modulators alone and in
combination with ethanol. The excitatory amino acid receptor antagonists,
dizocilpine [(+)-MK-801; (5R,1OS)-(+)-5-methyl-10,11-dihydro-5H
dibenzo[a,d]cyclohepten+ ++-5,10-imine], (+/-)-3-(2-carboxypiperazin-4-yl)-propyl
1-phosphonic acid (CPP), LY 326325 [(-)-(3S,4aR,6R,8R)-6-[2-(1(2)H-tetrazol-5-yl)
ethyl]-dec ahydroisoquinaline-3-carboxylic acid], LY 300164 [7,8-methylenedioxy-1
(4-aminophenyl)-4-methyl-3-acetyl-4,5-dihydro-2,3- benzodiazepine], and ACEA 1011
(5-chloro-7-trifluoromethyl-1,4-dihydro-2,3-quinoxalinedione) produced dose
dependent myorelaxation/ataxia in mice as determined using the horizontal wire
assay. Their behaviorally toxic doses (TD(50)s) were 0.41, 5.8, 33.0, 5.9, and
31.0 mg/kg, respectively, when administered alone i.p. In the presence of a sub
ataxic dose of ethanol (1.5 g/kg, i.p.), the TD(50)s of the excitatory amino acid
antagonists were 0.13, 1.8, 10.4, 1.3, and 14.0 mg/kg, respectively. Similarly,
the GABA(A) receptor positive modulators, pregnanolone, chlordiazepoxide, and
pentobarbital exhibited TD(50)s of 20.8, 4.6, and 29.7 mg/kg, respectively, when
administered alone and 2.7, 0.3, and 11.4 mg/kg, respectively, when administered
in the presence of ethanol. Thus, similar to the GABA(A) receptor positive
modulators, excitatory amino acid receptor antagonists exhibit the propensity to
interact with ethanol and to have their motor side-effects exaggerated.
PMID- 10193650
TI - Amygdalar neuropeptide Y Y1 receptors mediate the anxiolytic-like actions of
neuropeptide Y in the social interaction test.
AB - The effects of intra-amygdalar neuropeptide Y infusions were assessed in rats
using the social interaction test. Neuropeptide Y administered into the central
nucleus of the amygdala did not alter behavior, while injections into the
basolateral nucleus of the amygdala produced an increased social interaction
time. Furthermore, the anxiolytic-like effect was antagonized by co
administration of the potent neuropeptide Y Y1 receptor antagonist ((R)-N-[[4
(aminocarbonylaminomethyl)-phenyl]methyl]-N2-(diphen ylacetyl)-argininamide
trifluoroacetate) 3304, but not with the inactive enantiomer ((R)-N-[[4
(aminocarbonylaminomethyl)-phenyl]methyl]-N2-(diphen ylacetyl)-argininamide
trifluoroacetate) 3457. Therefore, neuropeptide Y produces an anxiolytic-like
effect in the social interaction test through neuropetide Y Y1 receptors located
in the basolateral amygdala.
PMID- 10193651
TI - Effects of some AMPA receptor antagonists on the development of tolerance in
epilepsy-prone rats and in pentylenetetrazole kindled rats.
AB - The non-selective alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid
(AMPA) receptor antagonists, 2,3-benzodiazepine derivatives CFM-1 (3,5-dihydro
7,8-dimethoxy-1-phenyl-4H-2,3-benzodiazepin-4-one) and CFM-2 (1-(4'-aminophenyl)
3,5-dihydro-7,8-dimethoxy-4H-2,3-benzodiazepin -4-one), following intraperitoneal
(i.p.) administration, were studied against audiogenic seizures in genetically
epilepsy-prone rats (GEPRs) or pentylenetetrazole induced kindling in rats. After
acute i.p. administration the ED50 values of CFM-1 against the clonic and tonic
phases of the audiogenic seizures 30 min after pretreatment were 40 (16-100) and
13 (8-25) micromol kg(-1), respectively. The animals used for chronic study were
treated i.p. daily (at 10 h) for 4 weeks with CFM-1 (20 or 50 micromol kg(-1)).
Chronic treatment for 2 weeks with CFM-1 gave ED50 values against clonic and
tonic seizures of 39 (22-69) and 16 (8-25) micromol kg(-1), respectively, whereas
chronic treatment for 4 weeks gave ED50 values against clonic and tonic seizures
of 42 (18-98) and 17 (7-41.3) micromol kg(-1), respectively. The duration of
anticonvulsant activity observed between 0.5 and 4 h following administration of
CFM-1 was similar for acute and chronic treatment. Two groups of Sprague-Dawley
rats received CMF (20 or 50 micromol kg(-1)) 30 min before a subconvulsant dose
of pentylentetrazole (25 mg kg(-1) i.p.) which is able to increase seizure
severity in control animals (i.e., chemical kindling). Pretreatment with CFM-2
delayed the progression of seizure rank during repeated administration of
pentylentetrazole. At the end of the period of repeated pentylentetrazole
treatment (6 weeks) the mean seizure score was 0 in vehicle treated controls, 4.3
in animals treated with vehicle + pentylentetrazole, 2.2 in rats treated
chronically with CFM-2 (20 micromol kg(-1) i.p.) + pentylentetrazole and 1.0 in
rats treated repeatedly with CFM-2 (50 micromol kg(-1) i.p.) +
pentylenetetrazole. CFM-2 was also able to antagonize the long-term increase in
sensitivity of the convulsant effects of GABA function inhibitors in
pentylentetrazole-kindled animals. Thus, the administration of a challenge dose
of pentylentetrazole (15 mg kg(-1) i.p.) or picrotoxin (1.5 mg kg(-1) i.p.) 15 or
30 days after the end of the repeated treatment showed that animals treated with
CFM-2 were significantly protected against seizures induced by pentylentetrazole
or picrotoxin. The data suggest that, following repeated treatment, tolerance to
the novel AMPA receptor antagonists does not develop (CFM-1 in genetically
epilepsy-prone rats and CFM-2 in the pentylentetrazole kindling model of
epilepsy). Thirteen minutes after drug injection on days 1, 14 and 28 of chronic
treatment the motor impairment induced by these compounds was studied with a
rotarod apparatus. The TD50 values for CFM-1 or CFM-2-induced impairment of
locomotor performance were similar following acute and repeated treatment. The
data also suggest that some novel 2,3-benzodiazepines may have clinical potential
for some types of epilepsy.
PMID- 10193652
TI - Changes of benzodiazepine receptors during chronic benzodiazepine administration
in humans.
AB - Changes of central type GABA(A)/benzodiazepine receptors during 24-day per-oral
administration of alprazolam (2 mg/day) were measured with single photon emission
computed tomography (SPECT) in nine healthy human subjects. Receptor densities
were measured on days -4 (baseline), 3, 10, 17 and 24. Comparison of baseline and
day 3 SPECT images was used to assess receptor occupancy; comparisons of the four
scans on medication were used to assess alterations in receptor levels. Clinical
effects were evaluated by subjective ratings of mood and the Hopkins verbal
learning test. Alprazolam induced sedation associated with a 16% receptor
occupancy. Unoccupied receptor levels decreased 10% from day 3 to day 10 but then
normalized to baseline values by day 17. Clinical effects showed corresponding
changes 1-2 weeks after the changes in the receptor. Thus, the decrease of
benzodiazepine receptor densities may be one of the major mechanisms for
tolerance development in humans.
PMID- 10193653
TI - Vagally-regulated gastric motor activity: evidence for kainate and NMDA receptor
mediation.
AB - Blockade of GABA(A) receptors in the dorsal vagal complex produces marked gastric
motor excitation. This effect is abolished by a prior microinjection of a non
selective excitatory amino acid receptor antagonist. Here we present functional
evidence for kainate and NMDA receptor-mediated gastric excitation in the dorsal
vagal complex. Microinjections into the dorsal vagal complex were performed in
alpha-chloralose-anesthetized rats using multi-barrelled glass micropipettes
while recording intragastric pressure and motility. Kainic acid (30 and 100 pmol
in 30 nl) and NMDA (100 and 300 pmol) produced dose-related increases in
intragastric pressure and motility. The gastric responses to kainate (30 pmol)
and NMDA were selectively abolished by prior microinjection 6,7
dinitroquinoxaline-2,3-dione (600 pmol, 60 nl) and DL-2-amino-5
phosphanopentanoic acid (2 nmol), respectively. Atropine (1 mg/kg, i.v.)
pretreatment blocked kainate-, NMDA- and L-glutamate-induced gastric excitation.
Thus, both kainate- and NMDA-receptors in the dorsal vagal complex can
independently cause vagally-mediated gastric motor excitation.
PMID- 10193654
TI - Involvement of sigma receptors in the modulation of the glutamatergic/NMDA
neurotransmission in the dopaminergic systems.
AB - Extracellular single-unit recordings and iontophoresis were used to examine the
effects of different selective sigma receptor ligands on dopaminergic and
glutamatergic N-methyl-D-aspartate (NMDA) neurotransmissions both in origin (A10
and A9 areas) and terminal (nucleus accumbens and caudate nucleus) regions of the
rat mesolimbic and nigrostriatal dopaminergic systems. The selective sigma1
receptor ligands 2-[4-(4-methoxy-benzyl)piperazin-1-yl-methyl]4-oxo[4H]-benzo-th
iazolin-2-one (S-21377), systemically administered (1.2 mg/kg, i.v., cumulative
dose), and 2[(4-benzyl piperazin-1-yl) mothyl] naphthalene, dichiorydrate (S
21378), iontophoretically applied, slightly increased the spontaneous firing rate
and potentiated the NMDA-induced neuronal activation of dopaminergic neurons in
the A9 and A10 regions. (+)N-cyclopropylmethyl-N-methyl-1,4-diphenyl-1-ethyl
butyl-2-N (JO-1784), another selective sigma1 receptor ligand produced no or
little effect in these areas. The systemic administration of the selective sigma2
receptor ligand 1,4-bis-spiro[isobenzofuran-1(3H), 4'-piperidin-1'yl]butane (Lu
29-252) (2 mg/kg, i.v., cumulative dose) did not modify the firing activity of A9
and A10 dopaminergic neurons, but significantly potentiated the NMDA-induced
increase in firing activity of A10 dopaminergic neurons. None of the sigma
receptor ligands tested had any effects on the dopamine-induced suppression of
firing. In the nucleus accumbens, the systemic administration of (JO-1784), (40
microg/kg, i.v.), (+)-pentazocine (30 microg/kg, i.v.), another selective sigma1
receptor ligand, and of the non selective sigma1 receptor ligand di-tolyl
guanidine (DTG) (20 microg/i.v.) produced a significant increase of NMDA-induced
neuronal activation. Microiontophoretic applications of JO-1784 also potentiated
the NMDA response. They also increased significantly the suppressant effect of
dopamine on NMDA and kainate-induced activations of accumbens neurons. In the
caudate nucleus, (+)-pentazocine, but not JO-1784, potentiated slightly the
neuronal response to NMDA. None of the sigma receptor ligands tested did modify
significantly the responses of caudate and accumbens neurons to kainate. These
findings suggest that at least two subtypes of sigma1 receptors may affect
differentially the glutamate NMDA neurotransmission in the terminal and origin
regions of the mesolimbic and nigrostriatal dopaminergic systems. These results
also demonstrate the existence of a functional interaction between sigma2 and
NMDA receptors in the A10 region.
PMID- 10193655
TI - Effect of intrathecal agmatine on inflammation-induced thermal hyperalgesia in
rats.
AB - Agmatine, an endogenous ligand, interacts both with the alpha2-adrenoceptors and
with the imidazoline binding sites. The effect of intrathecally administered
agmatine on carrageenan-induced thermal hyperalgesia was investigated by means of
a paw-withdrawal test in rats. The effect of agmatine on morphine-induced anti
hyperalgesia was also studied. Intrathecal agmatine in doses larger than 250
microg caused a decrease in the pain threshold, with vocalization and agitation
lasting for several hours in all animals. Agmatine alone at 1-100 microg did not
give rise to any change in the thermal withdrawal threshold in the contralateral
non-inflamed paw. Agmatine pretreatment was found to dose-dependently attenuate
the thermal hyperalgesia induced by intraplantar carrageenan. The effect of 100
microg agmatine was completely lost by 60 min, whereas the effect of 50 microg
was of similar magnitude but exhibited a longer duration. Agmatine posttreatment
had a slighter effect. Agmatine pretreatment (100 microg) together with 1 microg
morphine (subeffective dose) has significantly higher anti-hyperalgesic effect
then the individual compounds by themselves. These are the first data
demonstrating the behavioral and anti-hyperalgesic effects of intrathecal
agmatine. The results reveal important interactions between intrathecal agmatine
and opioids in thermal hyperalgesia.
PMID- 10193656
TI - Tiagabine antinociception in rodents depends on GABA(B) receptor activation:
parallel antinociception testing and medial thalamus GABA microdialysis.
AB - The effects of a new antiepileptic drug, tiagabine, (R)-N-[4,4-di-(3-methylthien
2-yl)but-3-enyl] nipecotic acid hydrochloride, were studied in mice and rats in
antinociceptive tests, using three kinds of noxious stimuli: mechanical (paw
pressure), chemical (abdominal constriction) and thermal (hot plate). In vivo
microdialysis was performed in parallel in awake, freely moving rats in order to
evaluate possible alterations in extracellular gamma-aminobutyric acid (GABA)
levels in a pain-modulating region, the medial thalamus. Systemic administration
of tiagabine, 30 mg kg(-1) i.p., increased nearly twofold the extracellular GABA
levels in rats and increased significantly the rat paw pressure nociceptive
threshold in a time-correlated manner. Dose-related significant tiagabine-induced
antinociception was also observed at the doses of 1 and 3 mg kg(-1) i.p. in the
mouse hot plate and abdominal constriction tests. The tiagabine antinociception
was completely antagonised by pretreatment with the selective GABA(B) receptor
antagonist, CGP 35348, (3-aminopropyl-diethoxy-methyl-phosphinic acid) (2.5
microg/mouse or 25 microg/rat i.c.v.), but not by naloxone (1 mg kg(-1) s.c.),
both administered 15 min before tiagabine. Thus, it is suggested that tiagabine
causes antinociception due to raised endogenous GABA levels which in turn
activate GABA(B) receptors.
PMID- 10193657
TI - Losartan and enalapril therapies enhance vasodilatation in the mesenteric artery
of spontaneously hypertensive rats.
AB - We studied the effects of 10-week long enalapril and losartan treatments (4 and
15 mg kg(-1) day(-1), respectively) on mesenteric arterial function in vitro in
spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). The
relaxations of noradrenaline-precontracted rings to acetylcholine, nitroprusside
and cromakalim were similar in WKY and enalapril- and losartan-treated SHR, and
more pronounced than in untreated SHR. The responses to acetylcholine were
attenuated by N(G)-nitro-L-arginine methyl ester in WKY and drug-treated SHR, but
were completely inhibited in untreated SHR. When hyperpolarization of smooth
muscle was prevented by KCl-induced precontractions, no differences were found in
the relaxations to acetylcholine and nitroprusside between the groups, and the
dilatations to cromakalim were abolished. Moreover, in noradrenaline
precontracted rings of drug-treated SHR, the addition of tetraethylammonium
attenuated the nitric oxide synthase and cyclooxygenase-resistant relaxations to
acetylcholine and abolished the enhanced dilatations to nitroprusside. In
conclusion, since the enhancement of vasorelaxation in enalapril- and losartan
treated SHR was abolished by conditions preventing hyperpolarization, the
improved vasodilatation following these therapies could be attributed to enhanced
vasodilatation via K+ channels in this model of hypertension.
PMID- 10193658
TI - Pharmacological effects of tolterodine on human isolated urinary bladder.
AB - Tolterodine, (R)-N,N-diisopropyl-3-(2-hydroxy-5-methylphenyl)-3
phenylpropanamine+ ++, is an antimuscarinic drug developed for the treatment of
overactive bladder with symptoms of frequency, urgency and urge incontinence. We
investigated the effects of tolterodine and its major active metabolite, DD 01
(PNU-200577), (R)-N,N-diisopropyl-3-(2-hydroxy-5-hydroxymethylphenyl)-3
phenylpropa namine, on the contractions induced by carbachol, KCl, CaCl2 and
electrical field stimulation in human isolated urinary bladder smooth muscles,
using the muscle bath technique. Specimens of human urinary bladder were obtained
from 20 patients who underwent total cystectomy due to malignant bladder tumor.
The detrusor preparations were taken from the intact part of the dome region of
the bladder. Carbachol (10(-9)-10(-2) M) caused concentration-dependent
contraction of human detrusor smooth muscles. Tolterodine (10(-9)-10(-6) M), DD
01 (10(-9)-10(-6) M), oxybutynin (10(-8)-10(-6) M), propiverine (10(-8)-10(-6)
M), atropine (10(-9)-10(-6) M), pirenzepine (10(-8)-10(-5) M), methoctramine (10(
8)-10(-5) M) and 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) (10(-9)-10(-6) M)
caused typical shifts to the right of the concentration-response curves for
carbachol, except for higher concentrations (10(-5) M) of oxybutynin and
propiverine, which caused a decrease of about 30% of the maximum contractile
responses to carbachol. All the slopes of the regression lines of Schild plots
were close to unity, and the rank order of pA2 values was: atropine = DD 01 =
tolterodine = 4-DAMP = oxybutynin > propiverine = pirenzepine > methoctramine.
Tolterodine (10(-9)-10(-6) M) and DD 01 (10(-9)-10(-6) M) did not inhibit the KCl
induced (80 mM) and CaCl2-induced (5 mM) contractions, while oxybutynin (10(-8)
10(-5) M) and propiverine (10(-8)-10(-5) M) significantly inhibited the
contractions. Electrical field stimulation (2-60 Hz) caused frequency-dependent
contraction of human detrusor smooth muscles, which were significantly inhibited
by various drugs. In the presence of 10(-6) M atropine, tolterodine and DD 01 did
not inhibit the residual contractions induced by electrical field stimulation at
any of the frequencies, while oxybutynin (10(-5) M) and propiverine (10(-5) M)
significantly inhibited the atropine-resistant part of the contractions. The
results suggest that the inhibitory effects of tolterodine and DD 01 are mediated
only by their antimuscarinic action, which is equal to that of oxybutynin and
significantly greater than that of propiverine, and that tolterodine and DD 01
have neither Ca2+ channel antagonist action nor inhibitory effect on the atropine
resistant part of the contractions in human detrusor smooth muscles. These
findings support the usefulness of tolterodine as a therapeutic drug for
overactive bladder with symptoms of frequency, urgency and urge incontinence.
PMID- 10193659
TI - Pharmacological evidence that neuropeptides mediate part of the actions of
scorpion venom on the guinea pig ileum.
AB - Severe human scorpion envenoming is characterised by instability of several
physiological systems and death. These manifestations are explained by the
ability of the venom toxins to activate sodium channels in nerve terminals with
the subsequent release of neurotransmitters, specially acetylcholine and
noradrenaline. However, there is evidence to suggest that other neurotransmitters
are also released. We now have sought evidence for a role of the substance P
receptor, the tachykinin NK1 receptor, in mediating part of the contractile
actions of Tityus serrulatus venom on the isolated guinea pig ileum. Scorpion
venom induced a significant elevation of baseline tension with frequent and
periodic superimposed contractions on the elevated baseline. Pretreatment with
atropine partially blocked the elevation in baseline and in the number of
superimposed contractions. These responses were also partially inhibited by the
tachykinin NK1 receptor antagonist, CP96,345 (the dihydrochloride salt of (2S,3S)
cis-2-(diphenylmethyl)-N-((2-methoxyphenyl)methyl)-1-az abicycol[2.2.2]octan-3
amine), but not by its inactive enantiomer, CP96,344 (the 2R-3R enantiomer of
CP96,345). Pretreatment with the combination of atropine and CP96,345 completely
inhibited the effects of the venom. Moreover, pretreatment with the combined
drugs abolished the effects of toxin gamma, a toxin purified from the venom.
Finally, another tachykinin NK1 receptor antagonist, RP67,580 ((3aR, 7ar)-7,7
diphenyl-2-[1-imino-2-(2-methoxy-phenyl)ethyl]perhydro isoindol-4-one),
significantly inhibited the venom-induced contractions. These results demonstrate
an important role for NK1 receptors in mediating part of the contractile effects
of the venom on guinea pig ileum. The release of neuropeptides may play an
important role in the systemic manifestations of severe envenoming.
PMID- 10193661
TI - Suppression of lipopolysaccharide-induced tumor necrosis factor-release and liver
injury in mice by naringin.
AB - Suppressive effects of naringin on lipopolysaccharide-induced tumor necrosis
factor (TNF) release followed by liver injury were investigated. Intraperitoneal
(i.p.) treatment with naringin prior to an intravenous (i.v.) challenge of
lipopolysaccharide significantly reduced serum TNF levels in a dose-dependent
manner and was the most effective when administered 60 min prior to
lipopolysaccharide challenge. Treatment with naringin 3 h prior to
lipopolysaccharide challenge resulted in complete protection from
lipopolysaccharide lethality in D-galactosamine-sensitized mice. Histological
estimation revealed that massive cell infiltration followed by severe injury
developed in the livers of lipopolysaccharide-treated and D-galactosamine-treated
mice unless they had been pretreated with naringin. Appearance of apoptotic cells
was also found to decrease by treatment with naringin. Increases in serum levels
of aspartate aminotransferase, alanine aminotransferase and creatine kinase,
responsible for lipopolysaccharide-induced liver injury, blocked by naringin
administration and the levels were nearly to the normal level. These results
indicate that action of naringin is mediated through suppression of
lipopolysaccharide-induced TNF production.
PMID- 10193660
TI - Effects of escins Ia, Ib, IIa, and IIb from horse chestnuts on gastric emptying
in mice.
AB - Inhibitory effects of the saponin fraction and its principal constituents, escins
Ia, Ib, IIa, and IIb, from horse chestnuts on gastric emptying were investigated
in mice loaded with a non-nutrient or nutrient meal. The saponin fraction and
escins Ia-IIb inhibited gastric emptying of a 1.5% carboxymethyl cellulose sodium
salt (CMC-Na) meal by 11.1-54.2% (12.5-200 mg/kg). Escins Ia-IIb (50 mg/kg) also
inhibited gastric emptying of a 40% glucose meal by 21.1-23.5% except for escin
Ia, a milk meal by 18.4-33.1%, and a 30% ethanol meal by 13.5-15.9%. The effects
of escins Ia-IIb on gastric emptying of the CMC-Na meal were attenuated by
pretreatment with streptozotocin (100 mg/kg, i.v.), capsaicin (75 mg/kg in total,
s.c.), or insulin (1 U/kg, s.c.). The effect of insulin was reduced by glucose (2
g/kg, i.v.) which can directly nourish the brain, but not by fructose (2 g/kg,
i.v.) which cannot be utilized by the brain. The effects of escins Ia-IIb (50
mg/kg) were overridden in 60% ethanol-loaded mice, in which the central nervous
system was suppressed by ethanol. These results suggest that capsaicin-sensitive
sensory nerves and central nervous system partly participate in the effects of
escins Ia-IIb.
PMID- 10193662
TI - Inhibition by auranofin of the production of prostaglandin E2 and nitric oxide in
rat peritoneal macrophages.
AB - In rat peritoneal macrophages, 12-O-tetradecanoylphorbol 13-acetate (TPA) (16.2
nM) stimulated production of both prostaglandin E2 and nitric oxide. TPA also
increased the levels of mRNA for cyclooxygenase-2 and inducible nitric oxide
synthase, suggesting that the increase in the production of prostaglandin E2 and
nitric oxide is due to the increase in the levels of mRNA for cyclooxygenase-2
and inducible nitric oxide synthase, respectively. The TPA-induced increase in
prostaglandin E2 production was partially inhibited by the inhibitor of nitric
oxide synthase L-N(G)-monomethyl-L-arginine acetate (L-NMMA), and the TPA-induced
increase in nitric oxide production was partially inhibited by the cyclooxygenase
inhibitor indomethacin, suggesting that both the production of prostaglandin E2
and nitric oxide in TPA-stimulated macrophages is influenced by each other. The
orally active chrysotherapeutic agent auranofin, at 3 and 10 microM, inhibited
the TPA-stimulated production of prostaglandin E2 and nitric oxide, and
suppressed the TPA-induced increase in the levels of mRNA for cyclooxygenase-2
and inducible nitric oxide synthase. These findings indicate that the inhibition
by auranofin of the TPA-stimulated production of prostaglandin E2 and nitric
oxide is due to the decrease in the levels of mRNA for cyclooxygenase-2 and
inducible nitric oxide synthase, respectively, and the interaction of the
production between prostaglandin E2 and nitric oxide may partly be involved in
the mechanism for the inhibition by auranofin of the production of both
prostaglandin E2 and nitric oxide.
PMID- 10193663
TI - Characterisation of the 5-HT receptor binding profile of eletriptan and kinetics
of [3H]eletriptan binding at human 5-HT1B and 5-HT1D receptors.
AB - The affinity of eletriptan ((R)-3-(1-methyl-2-pyrrolidinylmethyl)-5-[2
(phenylsulphonyl )ethyl]-1H-indole) for a range of 5-HT receptors was compared to
values obtained for other 5-HT1B/1D receptor agonists known to be effective in
the treatment of migraine. Eletriptan, like sumatriptan, zolmitriptan,
naratriptan and rizatriptan had highest affinity for the human 5-HT1B, 5-HT1D and
putative 5-ht1f receptor. Kinetic studies comparing the binding of [3H]eletriptan
and [3H]sumatriptan to the human recombinant 5-HT1B and 5-HT1D receptors
expressed in HeLa cells revealed that both radioligands bound with high
specificity (>90%) and reached equilibrium within 10-15 min. However,
[3H]eletriptan had over 6-fold higher affinity than [3H]sumatriptan at the 5-HT1D
receptor (K(D)): 0.92 and 6.58 nM, respectively) and over 3-fold higher affinity
than [3H]sumatriptan at the 5-HT1B receptor (K(D): 3.14 and 11.07 nM,
respectively). Association and dissociation rates for both radioligands could
only be accurately determined at the 5-HT1D receptor and then only at 4 degrees
C. At this temperature, [3H]eletriptan had a significantly (P<0.05) faster
association rate (K(on) 0.249 min(-1) nM(-1)) than [3H]sumatriptan (K(on) 0.024
min(-1) nM(-1)) and a significantly (P<0.05) slower off-rate (K(off) 0.027 min(
1) compared to 0.037 min(-1) for [3H]sumatriptan). These data indicate that
eletriptan is a potent ligand at the human 5-HT1B, 5-HT1D, and 5-ht1f receptors
and are consistent with its potent vasoconstrictor activity and use as a drug for
the acute treatment of migraine headache.
PMID- 10193664
TI - The effects of a point mutation of the beta2 subunit of GABA(A) receptor on
direct and modulatory actions of general anesthetics.
AB - The gamma-aminobutyric acid type A receptor (GABA(A) receptor) sites involved in
the direct and modulatory actions of general anesthetics remain to be elucidated.
The mutation of tyrosine at position 157 in the beta2 GABA(A) receptor subunit
was reported to reduce sensitivity to activation by GABA, but not pentobarbital.
We examined whether this mutation of the beta2 subunit (Tyr157-->Phe) affects the
direct and modulatory actions of other general anesthetics such as propofol and
etomidate. Using the two-electrode voltage clamp method, we recorded Cl- current
in Xenopus oocytes expressing alpha1beta2gamma2s and alpha1-mutated beta2gamma2s
subunits. The mutation of the beta2 subunit reduced the apparent affinity for
propofol. However, the mutation had no effect on both the direct actions of
pentobarbital and etomidate or on the modulatory actions of pentobarbital,
propofol and etomidate. These results suggest that unique loci may exist for the
direct action of propofol and that the GABA binding site may not mediate the
modulatory actions of general anesthetics at GABA(A) receptors.
PMID- 10193665
TI - Pharmacological profile of neuroleptics at human monoamine transporters.
AB - Using radioligand binding techniques, we determined the equilibrium dissociation
constants (K(D)) for 37 neuroleptics and one metabolite of a neuroleptic
(haloperidol metabolite) for the human serotonin, norepinephrine, and dopamine
transporters with [3H]imipramine, [3H]nisoxetine, and [3H]WIN35428, respectively.
Among neuroleptics, the four most potent compounds at the human serotonin
transporter were triflupromazine, fluperlapine, chlorpromazine, and ziprasidone
(K(D) 24-39 nM); and at the norepinephrine transporter, chlorpromazine, zotepine,
chlorprothixene, and promazine (K(D) 19-25 nM). At the human dopamine
transporter, only pimozide (K(D) = 69+/-3) ziprasidone (K(D) = 76+/-5) had
notable potency. These data may be useful in predicting therapeutic and adverse
effects, including drug interactions of neuroleptics.
PMID- 10193666
TI - Neuroprotective effects of nicergoline in immortalized neurons.
AB - We studied the potential neuroprotective action of nicergoline in immortalized
hypothalamic GT1-7 cells exposed to agents which deplete levels of reduced
glutathione, thus causing oxidative stress and cell death. Treatment with
diethylmaleate (1 mM), buthionine sulfoximine (500 microM) or menadione (10-50
microM) caused diffuse GT1-7 cell degeneration, as assessed by using either the 3
(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity
assay or the fluorescent dyes fluorescein diacetate and propidium iodide. Pre-
and/or co-exposure of the cells to nicergoline significantly prevented
diethylmaleate- or buthionine sulfoximine-induced neuronal death, whereas
nicergoline was ineffective against menadione-induced toxicity. This effect was
concentration-dependent and was mimicked by the classical antioxidants idebenone
and vitamin E, and did not depend on interference with protein kinase C.
Interestingly, the antineurodegenerative activity of nicergoline and vitamin E or
idebenone was not additive, suggesting that these compounds share some
intracellular mechanism(s) responsible for their protective effects. In
conclusion, the present data indicate that nicergoline has neuroprotective
activity, possibly mediated by the antioxidant activity of the molecule, and give
support to the potential use of nicergoline in the prevention and therapy of
neurodegenerative diseases.
PMID- 10193667
TI - Interaction between capsaicin and nitrate tolerance in isolated guinea-pig heart.
AB - Capsaicin-induced increases in heart rate and coronary flow were blocked by N(G)
nitro-L-Arg-methyl ester (30 mM) in Langendorff-perfused guinea-pig hearts.
Neither heart rate nor coronary flow changed by capsaicin in hearts from animals
made tolerant to the hypotensive effect of 30 microg/kg nitroglycerin by the
administration of 50 mg/kg nitroglycerin subcutaneously 4 times a day over 3
days. We conclude that the effector function of sensory nerves may deteriorate in
nitrate tolerance.
PMID- 10193668
TI - Influence of hypoxia and hyperoxia on the cardiovascular and lethal effects of
ethanol.
AB - The mutual potentiation of the hepatotoxic effects of ethanol and hypoxia raised
the question of whether such an interaction also occurs in the cardiovascular
system. Therefore, anaesthetized rats were infused intravenously with ethanol (25
mg/kg x min.) over 90 min. to reach blood ethanol concentrations between 2.2 and
2.6 g/l and were ventilated artificially either with room air, 10% O2/90% N2 or
100% O2. Under normoxic conditions, ethanol produced a slow decrease of mean
arterial blood pressure from 130 to 100 mmHg due to the decline in cardiac output
and stroke volume (-20%) while heart rate and peripheral resistance remained
unchanged. Hypoxia (arterial oxygen tension 35-38 mmHg) without ethanol produced
immediate hypotension (-60 mmHg) without decreasing the cardiac output, i.e. by
reducing peripheral resistance. In combination with ethanol, hypoxia produced an
even stronger hypotension (-90 mmHg) due to reduction in both cardiac output and
peripheral resistance. On the other hand, respiration with 100% O2 (arterial
oxygen tension about 500 mmHg) elevated peripheral resistance, attenuated ethanol
induced cardiodepression and prevented ethanol-induced hypotension. The lethal
doses of ethanol evaluated by infusing 75 mg/kg x min. ethanol until death
amounted to 4.1 g/kg with 10% O2, to 5.5 g/kg with 20% O2 (room air) and to 6.9
g/kg with 100% O2. Thus decrease in vascular contractility induced by hypoxia
combined with ethanol-induced cardiodepression may result in lethal
cardiovascular failure. Hyperoxia, on the other hand, counteracts ethanol-induced
cardiodepression and its acute toxicity by raising the vascular contractility.
PMID- 10193669
TI - Intestinal adsorption of levothyroxine by antacids and laxatives: case stories
and in vitro experiments.
AB - Two patients with hypothyroidism treated for upper dyspepsia and constipation
with aluminum hydroxide and magnesium oxide, respectively, presented a marked
increase in the serum concentration of thyroid stimulating hormone and low serum
thyroxine on a fixed dosage of levothyroxine. After discontinuation of
antacids/laxatives, thyroid stimulating hormone was again reduced indicating
interaction between levothyroxine and antacids/laxatives. In vitro studies
revealed a dose-related increased adsorption of levothyroxine by addition of a
combination of aluminum hydroxide, magnesium hydroxide and magnesium carbonate,
while no connection between levothyroxine and the addition of magnesium oxide,
alone, was found. This finding has major clinical consequences since 1) many
patients are treated with levothyroxine, 2) most patients do not tell physicians
that they take antacids/laxatives, and 3) consumption of antacids/laxatives in
patients with levothyroxine-treated hypothyroidism may lead to serious
undersubstitution with levothyroxine.
PMID- 10193670
TI - Effects on plasma angiotensin-converting enzyme activity and circulating renin of
lisinopril and enalapril alone and in combination with propranolol in healthy
volunteers.
AB - The effects on plasma angiotensin-converting enzyme activity and renin activity
of the two long-acting angiotensin-converting enzyme inhibitors, lisinopril and
enalapril, alone and in combination with propranolol were studied. In an open,
randomised, cross-over design 12 healthy volunteers received orally enalapril 20
mg alone, enalapril 20 mg in combination with propranolol 80 mg, lisinopril 20 mg
alone, and lisinopril 20 mg in combination with propranolol 80 mg. Plasma
angiotensin-converting enzyme activity and plasma renin activity were measured
for 24 h after each treatment period. Lisinopril and enalapril reduced plasma
angiotensin converting enzyme activity substantially and equally at six hr (-70%,
P<0.05) and 12 hr (-65%, P<0.05), irrespective of combination with propranolol.
At 24 hr plasma angiotensin-converting enzyme activity remained significantly
suppressed only after lisinopril (-60%, P<0.05). Plasma renin activity increased
almost ten times after ingestion of both angiotensin-converting enzyme
inhibitors, but the effect lasted significantly longer after lisinopril than
after enalapril. Beta-Adrenergic blockade blunted the effect on the increase in
plasma renin activity induced by both angiotensin-converting enzyme inhibitors.
Our results show that the effect of lisinopril on plasma angiotensin-converting
enzyme activity and plasma renin activity lasted longer than that of enalapril.
beta-Adrenergic blockade suppressed the effect on elevated plasma renin activity,
but did not influence the effect of angiotensin-converting enzyme inhibitors on
plasma angiotensin-converting enzyme activity.
PMID- 10193671
TI - Toxicity of fructose-1,6-bisphosphate in developing normoxic rats.
AB - Giving 500 mg/kg of fructose-1,6-bisphosphate intraperitoneally decreases
hypoxic/ischaemic CNS injury of neonatal rats. Before administering fructose-1,6
bisphosphate to human neonates, its toxicity must be determined in neonatal
animals. Thus, saline or 4,000, 6,000, or 8,000 mg/kg of fructose-1,6
bisphosphate was given intraperitoneally to normoxic 7 days old rats. One, 2, and
24 hr and 7 days later, blood Ca2+, PO(4)3-, blood urea nitrogen, and creatinine
concentrations, and aspartate aminotransferase activity were measured. Organ
pathology was determined at necropsy. Pups receiving 4,000 mg/kg of fructose-1,6
bisphosphate survived without evidence of injury or toxicity. All animals
receiving 8,000 mg/kg and 27 percent of those receiving 6,000 mg/kg of fructose
1,6-bisphosphate died. Surviving fructose-1,6-bisphosphate-treated animals grew
at the same rates and had similar weights as saline-treated animals. Nineteen
percent of pups given 6,000 or 8,000 mg/kg of fructose-1,6-bisphosphate had mild
perivascular fluid cuffing and/or microscopic pulmonary haemorrhage, but none of
the animals given 4,000 mg/kg of the compound had evidence of injury. No other
organ pathology was found in any of the animals. Renal and hepatic function were
normal in all animals. Fructose-1,6-bisphosphate administration was associated
with a significant increase in the fructose-1,6-bisphosphate concentration of
blood. Administering 4,000 to 8,000 mg/kg of fructose-1,6-bisphosphate
significantly decreased Ca2+ concentrations and increased PO(4)3- concentrations
1 and 2 hrs after fructose-1,6-bisphosphate administration. Similar changes in
Ca2+ and PO(4)3- concentrations occurred after the administration of 10 mmol/kg
of sodium phosphate. The wide margin of safety for fructose-1,6-bisphosphate (8
times the dose needed to prevent or reduce CNS injury) may render fructose-1,6
bisphosphate safe for use in neonates.
PMID- 10193672
TI - Gender aspects of liver slice incubations with N,N,N-triethylene-thiophosphamide
(Thio-TEPA) in rats and mice.
AB - This study was conducted to investigate if biotransformation of N,N,N-triethylene
thiophosphoramide (thio-TEPA) by liver slice incubations reflects the established
gender pattern for rat and mouse. Liver slices from rat and mice of both genders
were incubated with start concentrations of thio-TEPA of 5.2, 26, 52 and 104
microM for up to 240 min. Male rat liver slices eliminated thio-TEPA faster and
formed more TEPA than female liver slices at any concentration. No gender
difference was found for the elimination of thio-TEPA in mice, however, the
female liver slices formed less TEPA than the male ones. Apparently female rat
liver slices formed less TEPA than female mice liver slices. It is concluded that
the liver slice incubation system in a robust manner reflects gender differences
in rat drug biotransformation with special reference to thio-TEPA. It is also
confirmed that these aspects of gender are less pronounced in the examined mouse
species than in rats.
PMID- 10193673
TI - Cyclosporin A and trifluoperazine, two resistance-modulating agents, increase
ivermectin neurotoxicity in mice.
AB - The P-glycoprotein expressed in the blood-brain barrier has been associated with
the restricted access of many compounds to the central nervous system. Mice
lacking the mdr1a P-glycoprotein gene show an accumulation of various drugs in
brain tissues. P-glycoprotein is also correlated with the phenomenon of multidrug
resistance in tumour cells. To investigate the effects of drugs that modulate
multidrug resistance in the selective permeability of the blood-brain barrier,
mice were treated with cyclosporin A or trifluoperazine plus ivermectin, a P
glycoprotein substrate, that has a limited access to the central nervous system.
When mice received an injection of cyclosporin A (50 mg/kg, intraperitoneally) or
trifluoperazine (750 microg/kg, intraperitoneally) one hour prior to the
administration of ivermectin (10-15 mg/kg, intraperitoneally) there was an
increase in the acute toxicity of ivermectin. HPLC analysis of brain tissues
indicated that the ivermectin brain concentration was 2.5 times higher when mice
were previously treated with cyclosporin A (50 mg/kg). These results suggest that
attention should be given to the side effects of drugs that interact with P
glycoprotein and are commonly used clinically and also to the possibility of
creating a pharmacological gap in the blood-brain barrier that allows the access
of chemotherapeutic drugs to brain tumours.
PMID- 10193674
TI - Inhibition of lipid peroxidation by pindolol.
AB - Among beta-blockers, including atenolol, metaproterenol, pindolol and
propranolol, only pindolol strongly inhibited lipid peroxidation induced by
xanthine oxidase-hypoxanthine in the presence of adenosine-5'-phosphate-Fe3+. In
the reaction system, superoxide predominantly reduced iron because superoxide
dismutase strongly prevented the iron reduction. However, pindolol had no effect
on the superoxide-dependent iron reduction. Adding superoxide dismutase
immediately stopped the lipid peroxidation, indicating that superoxide is closely
connected with forming the initiator of xanthine oxidase-hypoxanthine-induced
lipid peroxidation. On the other hand, pindolol also inhibited lipid
peroxidation, whereas it did not react with superoxide, indicating that it
inhibited xanthine oxidase-hypoxanthine-induced lipid peroxidation by an
independent mechanism of superoxide. Pindolol sharply scavenged 2,2'-azino-bis-(3
ethylbenzothiazoline-6-sulfonate) radical cations, but the ability of pindolol to
scavenge peroxyl radicals of 2,2'-azobis(2-amidinopropane)-dihydrochloride and
2,2'-diphenyl-p-picrylhydrazyl radicals was low. In addition, pindolol did not
scavenge hydroxyl radicals at physiologically significant concentrations. These
results suggest that the ability of pindolol to inhibit lipid peroxidation was
due to scavenging carbon-centered radicals rather than peroxyl radicals.
PMID- 10193675
TI - The modulatory effect of spermine on the glutamate-NMDA receptor is regionally
variable in normal human adult cerebral cortex.
AB - The MK-801, glutamate and polyamine binding sites on the N-methyl-D-aspartate
class of glutamate receptors labelled with [3H]MK-801 were characterized in four
cortical areas (sensorimotor, superior temporal, mid-frontal and occipital) from
seven human adult control cases. Age, post-mortem delay, tissue storage time and
sex had no significant effects on any of the parameters measured. Dissociation
constants (K(D) values) for MK-801 showed similar mean values in the four
cortical areas, whereas receptor densities (B(max) values) showed significant
differences between sensorimotor or occipital and superior temporal or mid
frontal cortex. There were marked regional differences in the profiles of the
spermine- and glutamate-incremented enhancement of specific [3H]MK-801 binding.
The EC(50) for the glutamate enhancement was significantly higher in the
occipital than in the mid-frontal and sensorimotor cortex, whereas maximal
glutamate-enhanced binding values did not differ. The maximal enhancement of
[3H]MK-801 binding by spermine and glutamate varied between the cases, ranging
from zero to 40.4+/-9.3 fmol x mg protein(-1) for spermine, and from 85+/-5 to
111+/-10 fmol x mg protein(-1) for glutamate. Maximal spermine enhancement of
[3H]MK-801 binding was significantly more variable in superior temporal or mid
frontal than in sensorimotor or occipital cortex. The results suggest that N
methyl-D-aspartate receptor sites, especially the polyamine site, are
heterogeneous in human cerebral cortex, and show a high degree of regional and
individual variability.
PMID- 10193676
TI - Effect of erythromycin and itraconazole on the pharmacokinetics of oral
lignocaine.
AB - Lignocaine is metabolized by cytochrome P450 3A4 enzyme (CYP3A4), and has a
moderate to high extraction ratio resulting in oral bioavailability of 30%. We
have studied the possible effect of two inhibitors of CYP3A4, erythromycin and
itraconazole, on the pharmacokinetics of oral lignocaine in nine volunteers using
a cross-over study design. The subjects were given erythromycin orally (500 mg
three times a day), itraconazole (200 mg once a day) or placebo for four days. On
day 4, each subject ingested a single dose of 1 mg/kg of oral lignocaine. Plasma
samples were collected until 10 hr and concentrations of lignocaine and its major
metabolite, monoethylglycinexylidide were measured by gas chromatography. Both
erythromycin and itraconazole increased the area under the lignocaine plasma
concentration-time curve [AUC(0-infinity)] and lignocaine peak concentrations by
40-70% (P<0.05). Compared to placebo and itraconazole, erythromycin increased
monoethylglycinexylidide peak concentrations by approximately 40% (P<0.01) and
AUC(0-infinity) by 60% (P<0.01). The clinical implication of this study is that
erythromycin and itraconazole may significantly increase the plasma
concentrations and toxicity of oral lignocaine. The extent of the interaction of
lignocaine with these CYP3A4 inhibitors was, however, less than that of, e.g.
midazolam or buspirone, and it did not correlate with the CYP3A4 inhibiting
potency of erythromycin and itraconazole.
PMID- 10193677
TI - Cysteine transport in melanosomes from murine melanocytes.
AB - The synthesis of pheomelanin requires the incorporation of thiol-containing
compound(s) during the process of mammalian melanogenesis. Since melanins are
produced only in specialized, membrane-bound organelles, known as melanosomes,
such thiol donor(s) must cross the membrane barrier from the cytosol to the
melanosome interior. Cysteine and/or glutathione (GSH) were proposed as suitable
thiol donors, although uptake of these compounds into melanosomes was not
previously characterized. In this study, we show that cysteine is transported, in
a temperature- and concentration-dependent manner, across membranes of
melanosomes derived from murine melanocytes. Additional proof that cysteine
uptake results from a carrier-mediated process and is not due to simple diffusion
or to a membrane channel, was obtained in countertransport experiments, in which
melanosomes preloaded with cysteine methyl ester took up significantly more
[35S]cysteine than did unloaded controls. In contrast, we were unable to detect
any significant uptake of [35S]GSH over a wide concentration range, in the
presence or in the absence of reducing agent. This study is the first
demonstration of melanosomal membrane transport of cysteine, and it strongly
suggests that free cysteine is the thiol source utilized for pheomelanin
synthesis in mammalian melanocytes.
PMID- 10193678
TI - Hepatocyte growth factor/scatter factor-MET signaling in neural crest-derived
melanocyte development.
AB - The mechanisms governing development of neural crest-derived melanocytes, and how
alterations in these pathways lead to hypopigmentation disorders, are not
completely understood. Hepatocyte growth factor/scatter factor (HGF/SF) signaling
through the tyrosine-kinase receptor, MET, is capable of promoting the
proliferation, increasing the motility, and maintaining high tyrosinase activity
and melanin synthesis of melanocytes in vitro. In addition, transgenic mice that
ubiquitously overexpress HGF/SF demonstrate hyperpigmentation in the skin and
leptomenigenes and develop melanomas. To investigate whether HGF/ SF-MET
signaling is involved in the development of neural crest-derived melanocytes,
transgenic embryos, ubiquitously overexpressing HGF/SF, were analyzed. In HGF/SF
transgenic embryos, the distribution of melanoblasts along the characteristic
migratory pathway was not affected. However, additional ectopically localized
melanoblasts were also observed in the dorsal root ganglia and neural tube, as
early as 11.5 days post coitus (p.c.). We utilized an in vitro neural crest
culture assay to further explore the role of HGF/SF-MET signaling in neural crest
development. HGF/SF added to neural crest cultures increased melanoblast number,
permitted differentiation into pigmented melanocytes, promoted melanoblast
survival, and could replace mast-cell growth factor/Steel factor (MGF) in explant
cultures. To examine whether HGF/SF-MET signaling is required for the proper
development of melanocytes, embryos with a targeted Met null mutation (Met-/-)
were analysed. In Met-/- embryos, melanoblast number and location were not
overtly affected up to 14 days p.c. These results demonstrate that HGF/SF-MET
signaling influences, but is not required for, the initial development of neural
crest-derived melanocytes in vivo and in vitro.
PMID- 10193679
TI - A comparative study of the effect of pigment on drug toxicity in human choroidal
melanocytes and retinal pigment epithelial cells.
AB - The aim of this study was to investigate whether the presence of pigment affects
the sensitivity of pigmented cells of the eye, retinal pigment epithelium (RPE)
and choroidal melanocytes (CMs) to the cytotoxic effects of xenobiotic drugs. Two
approaches were used to compare pigmented versus unpigmented cells: RPE cells
were repigmented by phagocytosis of synthetic melanin; UVB irradiation was used
to induce an increase in pigment in both RPE and CMs. Three drugs known to induce
toxicity in the eye, tamoxifen, chloroquine and thioridazine, were used to assess
the sensitivity of cells to xenobiotic drugs. RPE cells were more resistant than
CMs to the cytotoxic effects of all three drugs by a factor of 5-fold for
tamoxifen, 7-fold for thioridazine and 30-fold for chloroquine. When RPE cells
were repigmented using synthetic melanin, their sensitivity to tamoxifen was
unchanged, they showed a slightly improved response to thioridazine (after 3 days
of incubation with this drug), but they showed greatly increased toxicity to
chloroquine (after 1 and 3 days of exposure to the drug), suggesting accumulation
of this latter drug on the synthetic melanin. UVB irradiation was used to achieve
an increase in the pigment content of both RPE and CMs. CMs were much more
sensitive to UVB than RPE cells. CMs appeared to synthesise pigment via DOPA
oxidase activity; RPE cells showed an increase in fluorescent material
independent of any detectable DOPA oxidase activity. Irrespective of the nature
of the pigment that UVB induced in melanocytes and RPE cells, their subsequent
response to thioridazine and chloroquine was unchanged by the presence of this
pigment.
PMID- 10193680
TI - Bicyclic monoterpene diols induce differentiation of S91 melanoma and PC12
pheochromocytoma cells by a cyclic guanosine-monophosphate-dependent pathway.
AB - Previously, we showed that 5-norbornene-2,2-dimethanol (5-NBene-2,2-DM) is an
effective inducer of melanogenesis in cultured cells and guinea-pig skin [Brown
et al. (1998) J. Invest. Dermatol., 110:428-437]. This study shows that 2,3
cis/exo-pinanediol (2,3-cs/ex-PinD) is a more effective inducer of melanogenesis
than 5-NBene-2,2-DM in S91 mouse melanoma cells. Furthermore, 2,3-cs/ex-PinD
appears to penetrate guinea-pig skin better than 5-NBene-2,2-DM and to induce
higher levels of pigmentation. Both 5-NBene-2,2-DM and 2,3-cs/ex-PinD induce
synthesis of nitric oxide (NO) in S91 cells, and the melanogenic activity of both
compounds is reduced by inhibitors of the NO/cyclic guanosine monophosphate
(cGMP)/protein kinase(PK) G signaling pathway, but not by inhibitors of the PKC
or PKA pathways. Thus, these bicyclic monoterpene diols appear to induce
melanogenesis by the same pathway in S91 cells as that shown previously for
ultraviolet radiation in melanocytes (Romero-Graillet et al. (1996) J. Biol.
Chem., 271:28052-28056). These compounds also induce NO synthesis, neurite
outgrowth, and tyrosine hydroxylase activity in PC12 pheochromocytoma cells.
Neurite outgrowth in PC12 cells is blocked by the guanylate cyclase inhibitor,
LY83583 (6-anilino-2,8-quinolinequinone), indicating that, similar to S91 cells,
the induction of morphological differentiation of PC12 cells by bicyclic
monoterpene diols is regulated by a cGMP-dependent pathway.
PMID- 10193681
TI - The emergence of pigment cell biology: a personal view.
AB - This is a semi-autobiographical coverage of my research career in pigment cell
biology presented in the context of the emergence and growth of the discipline.
This anecdotal presentation tells about some historical personages in the field.
My undergraduate studies at the University of Rochester are related to my
graduate work at the University of Iowa. I tell how my dissertation research was
derived from a marriage between my interests in experimental embryology and the
new field of comparative endocrinology. My early years of research at Iowa and as
a young faculty member in Zoology at the University of Arizona were much
concerned with the evolution of our knowledge of the chemistry and biology of
melanocyte-stimulating hormone (MSH), especially concerning the pigment cells of
lower vertebrates. Our developmental, structural, functional, and biochemical
characterization of vertebrate chromatophores is described, as is our elucidation
of the dermal chromatophore unit. The direct effects of light on changes in
pigmentation are considered in descriptions of both the tail-darkening reaction
and the role of the pineal gland in melanophore control. Emphasis is placed on
the developmental biology of pigmentation, especially on the concept that all
pigment cells are derived in common from a stem cell of neural-crest origin,
whose expression is influenced by factors, such as melanization-inhibiting factor
(MIF), localized in specific areas of the skin to thus produce specific
pigmentation patterns. This research is considered in light of what is known
about the agouti locus and MSH in the expression of mammalian pigmentation
patterns. Part of my work has included ecological considerations, and some of
this is touched upon. My role as founder of the journal 'Pigment Cell Research',
is presented briefly, as is my involvement in the XIIIth International Pigment
Cell Conference and in the establishment of both the International Pigment Cell
Society and the International Federation of Pigment Cell Societies. Finally, I
comment on the future of research in pigmentation.
PMID- 10193682
TI - Is there a role for antibiotics in the treatment of patients with rheumatoid
arthritis?
AB - Despite many advances in the understanding and treatment of rheumatoid arthritis,
its pathophysiology remains incompletely understood. An infectious aetiology of
rheumatoid arthritis has long been postulated but, even though many continue to
believe that there is a 'triggering agent for rheumatoid arthritis', none has
been identified. Currently, both sulfasalazine and minocycline have been shown to
be effective treatments for rheumatoid arthritis and are being used increasingly.
In the case of minocycline, it appears that its ability to inhibit
metalloproteases is an important characteristic that may account for some or part
of its action against rheumatoid arthritis. Whether the antibacterial effects of
these drugs or others are important in the treatment of rheumatoid arthritis
continues to be investigated.
PMID- 10193683
TI - Antibiotics for myocardial infarction? A possible role of infection in
atherogenesis and acute coronary syndromes.
AB - The role of inflammatory mechanisms in the initiation, progression and clinical
expression of atherosclerosis is increasingly appreciated. With this awareness,
the possibility that acute or chronic infection may initiate or modulate these
processes in an active area of investigation. Infectious organisms may influence
the atherosclerotic process through direct local effects on the coronary
endothelium, on vascular smooth muscle cells and on macrophages in the
atherosclerotic lesion. Infection may also exert systemic effects by inducing the
elaboration of cytokines, the creation of a hypercoagulable state and by
activating monocytes, causing possible transmission of infectious material to
atherosclerotic lesions. Macrophages may then elaborate multiple mediators which
destabilise plaque, promoting rupture and progression. Seroepidemiological data
have identified associations between clinically active atherosclerosis and
evidence of infection with Helicobacter pylori, Chlamydia pneumoniae and some
herpesviridae. In addition, pathological examinations have demonstrated the
presence of infectious organisms in coronary artery plaques. Cytomegalovirus, for
example, has been identified pathologically to be associated with transplant
vasculopathy and with an increased risk of restenosis following coronary
intervention. Finally, recent pilot trials have demonstrated that macrolide
antibacterial treatment directed against C. pneumoniae reduces the risk of
recurrent coronary events. Infectious organisms may therefore influence
atherogenesis through multiple pathways, and pathological and seroepidemiological
investigations provide evidence of this association. Future large-scale clinical
trials are needed to further evaluate the evidence of causality and the efficacy
of antibacterial therapy for coronary artery disease.
PMID- 10193684
TI - Chemoprotectants: a review of their clinical pharmacology and therapeutic
efficacy.
AB - Dose-limiting toxicity secondary to antineoplastic chemotherapy is due to the
inability of cytotoxic drugs to differentiate between normal and malignant cells.
The consequences of this may include impairment of patient quality of life,
because of toxicity, and reduced tumour control because of the inability to
deliver adequate dose-intensive therapy against the cancer. Specific examples of
toxicity against normal tissues include cisplatin-related neurotoxicity and
nephrotoxicity, myelotoxicity secondary to treatment with alkylating agents and
carboplatin, oxazaphosphorine-induced haemorrhagic cystitis, and cumulative dose
related cardiac toxicity secondary to anthracycline treatment. Chemoprotectants
have been developed as a means of ameliorating the toxicity associated with
cytotoxic agents by providing site-specific protection for normal tissues,
without compromising antitumour efficacy. Clinical trials with toxicity
protectors must include sufficient dose-limiting events for study, and assessment
of both toxicity (allowing for measurement of efficacy of protection) and
antitumour effect. Several chemoprotective compounds have now been extensively
investigated, including dexrazoxane, amifostine, glutathione, mesna and ORG 2766.
Dexrazoxane appears to complex with metal co-factors including iron, to reduce
the incidence of anthracycline-induced cardiotoxicity, allowing the delivery of
higher cumulative doses of anthracyclines without the expected consequence of
cardiomyopathy. Numerous studies have demonstrated that sulfur-containing
nucleophiles, including amifostine, glutathione, and mesna can specifically bind
cisplatin- or alkylating agent-generated free radicals or alkylating agent
metabolites to reduce the incidence of cisplatin-associated neurotoxicity and
nephrotoxicity, or alkylating agent-associated myelosuppression and urothelial
toxicity. These studies, in the majority of instances, have not revealed any
evidence of reduction in antitumour efficacy. Further randomised trials are
required to identify the optimal role of chemoprotectants when used alone or in
combination with other toxicity modifiers including haemopoietic growth factors.
PMID- 10193685
TI - Prospects for the therapeutic use of anticancer vaccines.
AB - Although a century has passed since initial attempts were made to stimulate the
immune system to destroy tumour, the immunotherapy of cancer is still in the
early stages. Historically, a variety of specific and nonspecific
immunostimulatory strategies have been administered with only modest clinical
success. However, recent advances in tumour immunology, most notably the
identification of genes encoding for cancer regression antigens, have paved the
way for the development of a variety of novel and specific vaccine approaches.
These include vaccines based on tumour cells, carbohydrates, peptides and heat
shock proteins, DNA-based vaccination, and the use of recombinant bacteria and
viruses to deliver antigens or the DNA coding for them. While several of these
approaches have yielded exciting clinical results, a number of immunological and
host obstacles to the successful application of cancer vaccines remain. Further
research is needed on the optimum choice of antigen, delivery vector, adjuvant
and administration regimen.
PMID- 10193686
TI - A practical guide to the management of oesophageal varices.
AB - Bleeding oesophageal varices are a frequent and sometimes fatal complication of
portal hypertension. Prompt resuscitation and arrest of haemorrhage are the
immediate short term priorities. Vasoactive therapy to reduce portal pressure is
administered on presentation. Early endoscopy is necessary to make a definitive
diagnosis and initiate appropriate therapy; usually emergency sclerotherapy or
banding. After the acute bleeding episode, follow-up therapy is instituted either
to obliterate the varices by sclerotherapy or banding, or to chronically lower
portal pressure and hence reduce the risk of bleeding pharmacologically; a
combination of both strategies may be also used. Active surveillance of those at
risk of developing varices is advocated. Long term beta-blocker therapy has been
demonstrated to be effective in both the primary prevention of variceal
haemorrhage and the prevention of rebleeding in those who have already bled.
Despite a multitude of therapeutic regimes and ongoing clinical trials, mortality
from this condition remains disappointingly high.
PMID- 10193688
TI - Moxifloxacin.
AB - Moxilloxacin is a new fluoroquinolone antibacterial agent with a broad spectrum
of activity, encompassing gram-negative and gram-positive bacteria. It has
improved activity against gram-positive species (including staphylococci,
streptococci, enterococci) and anaerobes compared with ciprofloxacin. This is
offset by slightly lower activity against pseudomonal species and
Enterobacteriaceae. In common with other fluoroquinolones, moxifloxacin attains
good penetration into respiratory tissues and fluids and its bioavailability is
substantially reduced by coadministration with an antacid or iron preparation.
However, moxifloxacin does not interact with theophylline or warfarin. In
clinical trials in patients with community-acquired pneumococcal pneumonia (CAP),
acute exacerbations of chronic bronchitis (AECB) or acute sinusitis, moxifloxacin
400 mg once daily achieved bacteriological and/or clinical success rates of
approximately 90% or higher. Moxifloxacin was as effective as amoxicillin 1 g 3
times daily and clarithromycin 500 mg twice daily in CAP and as effective as
clarithromycin in AECB. In patients with sinusitis, a 7-day course of
moxifloxacin 400mg once daily was as effective as a 10-day course of cefuroxime
axetil 250mg twice daily. In contrast to some other fluoroquinolones,
moxifloxacin appears to have a low propensity for causing phototoxic and CNS
excitatory effects. The most common adverse events are gastrointestinal
disturbances.
PMID- 10193689
TI - Fomivirsen.
AB - Fomivirsen (ISIS 2922) is an antisense oligonucleotide which specifically
inhibits replication of human cytomegalovirus. It achieves this by binding to
complementary sequences on messenger RNA transcribed from the major immediate
early transcriptional unit of the virus. It is being developed for the treatment
of cytomegalovirus retinitis. Mean maximum retinal concentrations of fomivirsen
occurred approximately 2 days after a single intravitreal injection in monkeys.
The elimination half-life of fomivirsen (after a single 115 microg dose) in
monkey retina was 78 hours. Fomivirsen, administered as an intravitreal
injection, significantly delayed progression of cytomegalovirus retinitis in
patients with AIDS in preliminary clinical trials. In 18 patients with newly
diagnosed, unilateral, peripheral cytomegalovirus retinitis treated with
fomivirsen 165 microg once weekly for 3 weeks, then 165 microg every second week,
the median time to disease progression was significantly longer than in 10
patients in whom fomivirsen treatment was deferred until early disease
progression (71 vs 14 days). In patients with advanced, refractory, sight
threatening disease, treatment with fomivirsen 330 microg once weekly for 3 weeks
and then 330 microg every 2 weeks (n = 34) or 330 microg on days 1 and 15 and
then monthly (n = 20) significantly delayed disease progression. The interpolated
median time to disease progression was 90 days in both treatment groups. The most
common adverse events reported in clinical trials of fomivirsen were increased
intraocular pressure and mild to moderate intraocular inflammation. These events
were generally transient or reversible with topical steroid treatment.
PMID- 10193687
TI - Managing resistance to anti-HIV drugs: an important consideration for effective
disease management.
AB - Current recommendations for the treatment of HIV-infected patients advise highly
active antiretroviral therapy (HAART) consisting of combinations of 3 or more
drugs to provide long-term clinical benefit. This is because only a complete
suppression of virus replication will be able to prevent virus drug resistance,
the main cause of drug failure. Virus drug resistance may remain a cause of
concern in patients who have already received suboptimal mono- or bitherapy, or
for patients who do not experience complete shut-down of virus replication under
HAART. For these patients, replacement of one combination therapy regimen by
another at drug failure, taking into account the existing resistance profile,
will be needed. The development of new drugs will remain necessary for those
patients who have failed to respond to all currently available drugs, as will be
the institution of more effective and less toxic HAART regimens.
PMID- 10193690
TI - Oral delayed-release mesalazine: a review of its use in ulcerative colitis and
Crohn's disease.
AB - Oral delayed-release mesalazine is an enteric-coated formulation which releases
mesalazine in the terminal ileum and colon. Up to 74% of patients with mild to
moderately active ulcerative colitis experience endoscopic or symptomatic
improvement (including remission) or both when treated with oral delayed-release
mesalazine 2.4 to 4.8 g/day. There is a trend towards a better response in
patients receiving higher daily dosages of oral delayed-release mesalazine,
especially in patients with active distal disease. In patients with left-sided
ulcerative colitis, oral balsalazide 6.75 g/day appears to be more effective than
oral delayed-release mesalazine 2.4 g/day, but a higher dosage of oral delayed
release mesalazine 4.8 g/day may provide additional benefit in these patients.
Oral delayed-release mesalazine 0.8 to 4.4 g/day appears to be as effective as
sulfasalazine 2 to 4 g/day, prolonged-release mesalazine 1.5 g/day or balsalazide
3 g/day in maintaining remission in patients with ulcerative colitis. The optimal
dosage of oral delayed-release mesalazine for the maintenance of remission is
unclear. However, oral delayed-release mesalazine 1.6 g/day with rectal
mesalazine 4g, administered twice weekly, was more effective than oral drug alone
in maintaining remission in patients at high risk of relapse. In patients with
left-sided or distal disease oral olsalazine 1 g/day appeared to be superior to
oral delayed-release mesalazine 1.2 g/day for maintenance of symptomatic
remission. Limited data in patients with Crohn's disease have shown oral delayed
release mesalazine 0.4 to 4.8 g/day to be an effective therapy for active disease
(remission in up to 45% of patients) and for quiescent disease (relapse in 34% of
recipients over a duration of up to 12 months). Preliminary data indicate that
oral delayed-release mesalazine 2.4 g/day is effective in preventing
postoperative recurrence of Crohn's disease. Oral delayed-release mesalazine is
effective and well tolerated in sulfasalazine-intolerant patients with ulcerative
colitis or Crohn's disease. CONCLUSIONS: Oral delayed-release mesalazine is
effective in patients with mild to moderately active or quiescent ulcerative
colitis. Available data suggest that patients with left-sided or distal
ulcerative colitis are likely to require higher daily dosages of oral delayed
release mesalazine or supplementation with rectal mesalazine. Oral delayed
release mesalazine also appears to be effective in active and quiescent Crohn's
disease. The drug is well tolerated and it appears to be effective in
sulfasalazine-intolerant patients.
PMID- 10193693
TI - Retrospective motion correction in digital subtraction angiography: a review.
AB - Digital subtraction angiography (DSA) is a well-established modality for the
visualization of blood vessels in the human body. A serious disadvantage of this
technique, inherent to the subtraction operation, is its sensitivity to patient
motion. The resulting artifacts frequently reduce the diagnostic value of the
images. Over the past two decades, many solutions to this problem have been put
forward. In this paper, we give an overview of the possible types of motion
artifacts and the techniques that have been proposed to avoid them. The main
purpose of this paper is to provide a detailed review and discussion of
retrospective motion correction techniques that have been described in the
literature, to summarize the conclusions that can be drawn from these studies,
and to provide suggestions for future research.
PMID- 10193692
TI - Eptifibatide: a review of its use in patients with acute coronary syndromes
and/or undergoing percutaneous coronary intervention.
AB - Eptifibatide, a cyclic peptide, is a highly specific, intravenously administered
glycoprotein (GP) IIb/IIIa receptor antagonist. By preventing fibrinogen binding
to the GP IIb/IIIa receptor, eptifibatide inhibits platelet aggregation and
prevents thrombus formation. Clinically, the drug is used as an adjunct to
heparin and aspirin. The PURSUIT trial, conducted in >10,000 patients with
unstable angina or non-Q-wave myocardial infarction (MI), showed that
eptifibatide (180 microg/kg bolus then 2 microg/kg/min infusion for < or =72
hours) reduces the 30-day risk of death or nonfatal MI, with this benefit
apparent at 96 hours. The absolute reduction in this end-point of 1.5% persisted
at 6 months. The drug is effective in patients undergoing percutaneous coronary
intervention (PCI), and, as shown in the North American subgroup, in patients in
whom medical management is appropriate. Eptifibatide is also beneficial in
patients undergoing PCI, whether or not they have unstable angina or non-Q-wave
MI. In a dosage of 135 microg/kg then 0.5 microg/kg/min for 24 hours,
eptifibatide reduced the 30-day risk of a combined end-point (death, nonfatal MI
and urgent or emergency coronary interventions) by 2.5% (absolute reduction) in
patients undergoing PCI in the IMPACT-II trial, when measured by per-protocol
(patients treated), but not intent-to-treat, analysis. The drug also decreased
the incidence of abrupt vessel closure and ischaemic cardiovascular complications
in the first 24 hours (the period of greatest risk). Bleeding episodes are the
most common adverse event associated with eptifibatide therapy. Although the
incidence of major bleeding is increased with eptifibatide, most bleeding
episodes are minor and occur at the vascular access site. The drug is not
associated with an excess of intracranial bleeds, stroke or thrombocytopenia,
does not appear to increase bleeding risk in patients undergoing coronary artery
bypass graft (CABG), and does not cause antibody formation. Limited data suggest
that eptifibatide may improve coronary flow when combined with alteplase in
patients with acute Q-wave MI, but the possibility of increased bleeding with
eptifibatide plus thrombolytics should be borne in mind. CONCLUSIONS: Intravenous
eptifibatide, when combined with aspirin and heparin, reduces the 30-day risk of
ischaemic events in patients with unstable angina and non-Q-wave MI and decreases
ischaemic cardiovascular complications at the time of greatest risk in patients
undergoing PCI. With its acceptable tolerability profile eptifibatide is a
suitable option as a short term adjunct in these clinical settings. Whether
eptifibatide in combination with fibrolysis may improve outcome in patients with
acute Q-wave MI has yet to be determined.
PMID- 10193691
TI - Troglitazone: a review of its use in the management of type 2 diabetes mellitus.
AB - Troglitazone is the first of a new group of oral antidiabetic drugs, the
thiazolidinediones, and is indicated for the treatment of patients with type 2
(non-insulin-dependent) diabetes mellitus. Troglitazone acts by enhancing the
effects of insulin at peripheral target sites and, unlike the sulphonylurea
drugs, is not associated with hypoglycaemia when administered as monotherapy.
Clinical trials with troglitazone (usually 200 to 600 mg/day) in patients with
type 2 diabetes mellitus consistently showed marked improvement in glycaemic
control, as well as reductions in fasting serum insulin, C-peptide and
triglyceride levels. Comparative studies with either glibenclamide (glyburide) or
metformin indicated similar glycaemic control with troglitazone or these agents.
Serum insulin levels were lower with troglitazone than with glibenclamide.
Clinical trials of up to approximately 2 years' duration showed that glycaemic
control is maintained with troglitazone on a long term basis. In general,
troglitazone is well tolerated by the majority of patients. However,
discontinuation of troglitazone because of elevated liver enzyme levels occurs in
approximately 2% of patients receiving the drug, and frequent monitoring of liver
enzymes is required (e.g. at least 11 times during the first year of therapy).
Among patients who started troglitazone therapy in 1998 (after the incorporation
of a boxed warning and increased monitoring requirements in the product
labelling), the estimated risk of liver-related death is approximately 1 in
100,000. CONCLUSIONS: Troglitazone improves the ability of target cells to
respond to insulin. The drug has been shown to improve glycaemic control in
patients with type 2 diabetes mellitus when used as monotherapy or in combination
with other oral antidiabetic drugs or insulin, and its efficacy is similar to
that of glibenclamide or metformin. Although troglitazone is generally well
tolerated, close monitoring of liver enzyme function is required to minimise the
rare occurrence of serious hepatic dysfunction. Drug acquisition and liver
function monitoring costs, as well as potential adverse effects, are important
factors that may ultimately determine the precise place of troglitazone in the
management of type 2 diabetes mellitus. Nevertheless, as the first member of a
new class of oral antidiabetic agents, the thiazolidinediones, troglitazone
offers an effective treatment option in patients with type 2 diabetes mellitus
through its action of improving insulin sensitivity.
PMID- 10193694
TI - Perception of temporally filtered X-ray fluoroscopy images.
AB - For noisy X-ray fluoroscopy image sequences we quantitatively evaluated image
quality after digital temporal filtering to reduce noise. Using an experimental
paradigm called a reference/test adaptive forced-choice method we compared
detectability of stationary low-contrast disks in filtered and unfiltered,
computer-generated image sequences. In the first experiment, a low-pass first
order recursive filter used in X-ray fluoroscopy was found to be much less
effective at enhancing detectability than predicted from the reduction of display
noise variance, a common measurement of filter effectiveness. Detectability was
reasonably predicted by a nonprewhitening human-observer model (NPW-HVS) that
included an independently determined human temporal-contrast-sensitivity
function. In another experiment, designed to test models over a range of temporal
frequencies, we used paired high-pass and low-pass temporal filters that both
reduced noise variance by 25%. The high-pass filter was artificially applied to
the noise only and greatly improved detectability, while the low-pass filter had
little effect. The human-observer model quantitatively described the
measurements, but classical prewhitening and nonprewhitening signal detectors did
not. As compared to the nonprewhitening, spatio-temporal matched filter, human
observer efficiency was low and variable at 2.1%, 2.9%, and 0.06% for 60 frames
of unfiltered low-pass and high-pass noise, respectively. As compared to this
detector, humans were not very effective at combining information across frames.
On the other hand, signal to noise ratios (SNR's) from the human-observer model
were comparable to human performance, and efficiencies were reasonably constant
at 40%, 52%, and 32%, respectively. We conclude that it is imperative to include
human-observer models and experiments in the analysis of noise-reduction
filtering of noisy image sequences, such as X-ray fluoroscopy.
PMID- 10193695
TI - Global, voxel, and cluster tests, by theory and permutation, for a difference
between two groups of structural MR images of the brain.
AB - We describe almost entirely automated procedures for estimation of global, voxel,
and cluster-level statistics to test the null hypothesis of zero neuroanatomical
difference between two groups of structural magnetic resonance imaging (MRI)
data. Theoretical distributions under the null hypothesis are available for 1)
global tissue class volumes; 2) standardized linear model [analysis of variance
(ANOVA and ANCOVA)] coefficients estimated at each voxel; and 3) an area of
spatially connected clusters generated by applying an arbitrary threshold to a
two-dimensional (2-D) map of normal statistics at voxel level. We describe novel
methods for economically ascertaining probability distributions under the null
hypothesis, with fewer assumptions, by permutation of the observed data. Nominal
Type I error control by permutation testing is generally excellent; whereas
theoretical distributions may be over conservative. Permutation has the
additional advantage that it can be used to test any statistic of interest, such
as the sum of suprathreshold voxel statistics in a cluster (or cluster mass),
regardless of its theoretical tractability under the null hypothesis. These
issues are illustrated by application to MRI data acquired from 18 adolescents
with hyperkinetic disorder and 16 control subjects matched for age and gender.
PMID- 10193696
TI - Longitudinal sampling and aliasing in spiral CT.
AB - Although analyses of in-plane aliasing have been done for conventional computed
tomography (CT) images, longitudinal aliasing in spiral CT has not been properly
investigated. We propose a mathematical model of the three-dimensional (3-D)
sampling scheme in spiral CT and analyze its effects on longitudinal aliasing. We
investigated longitudinal aliasing as a function of the helical-interpolation
algorithm, pitch, and reconstruction interval using CT simulations and actual
phantom scans. Our model predicts, and we verified, that for a radially uniform
object at the isocenter, the spiral sampling scheme results in spatially varying
cancellation of the aliased spectral islands which, in turn, results in spatially
varying longitudinal aliasing. The aliasing is minimal at the scanner isocenter,
but worsens with distance from it and rapidly becomes significant. Our results
agree with published results observed at the isocenter of the scanner and further
provide new insight into the aliasing conditions at off-isocenter locations with
respect to the pitch, interpolation algorithm, and reconstruction interval. We
conclude that longitudinal aliasing at off-isocenter locations can be
significant, and that its magnitude and effects cannot be predicted by
measurements made only at the scanner isocenter.
PMID- 10193697
TI - A unified reconstruction framework for both parallel-beam and variable focal
length fan-beam collimators by a Cormack-type inversion of exponential radon
transform.
AB - A variety of inversions of exponential Radon transform has been derived based on
the circular harmonic transform in Fourier space by several research groups.
However, these inversions cannot be directly applied to deal with the
reconstruction for fan-beam or variable-focal-length fan-beam collimator
geometries in single photon emission computed tomography (SPECT). In this paper,
we derived a Cormack-type inversion of the exponential Radon transform by
employing the circular harmonic transform directly in the projection space and
the image space instead of the Fourier space. Thus, a unified reconstruction
framework is established for parallel-, fan-, and variable-focal-length fan-beam
collimator geometries. Compared to many existing algorithms, the presented one
greatly mitigates the difficulty of image reconstruction due to the complicated
collimator geometry and significantly reduces the computational burden of the
special functions, such as Chebyshev or Bessel functions. By the well-established
fast-Fourier transform (FFT), our algorithm is very efficient, as demonstrated by
several numerical simulations.
PMID- 10193698
TI - Energy dependence of nonstationary scatter subtraction--restoration in high
resolution PET.
AB - In previous works, the determination of object and detector scatter kernels from
line source measurements was described and their application in scatter
correction was investigated. It was also shown that low energy data contains a
large fraction of useful events (true and detector scatter events). In the
present work, data acquired in multispectral mode was summed in single broad
energy windows of lower energy thresholds varying from 129 to 516 keV in steps of
43 keV and a constant upper energy threshold of 645 keV. Line-source projections
were fitted by extracting the object and detector scatter kernels as a function
of energy threshold. These kernels were then used to process scatter by the
nonstationary convolution subtraction-restoration method in phantom images. After
scatter correction, the sensitivity is found to increase by up to 64% at the
lower threshold of 129 keV, relative to the conventional photopeak energy window
(344-645 keV). Whereas contrast and spatial resolution are degraded as the energy
discriminator is lowered, such degradation is fully recovered by the scatter
correction. As a result of scatter correction, the noise increases
insignificantly in hot regions but substantially in cold regions, in proportion
of the amount of scatter.
PMID- 10193699
TI - Segmentation of medical images using LEGION.
AB - Advances in visualization technology and specialized graphic workstations allow
clinicians to virtually interact with anatomical structures contained within
sampled medical-image datasets. A hindrance to the effective use of this
technology is the difficult problem of image segmentation. In this paper, we
utilize a recently proposed oscillator network called the locally excitatory
globally inhibitory oscillator network (LEGION) whose ability to achieve fast
synchrony with local excitation and desynchrony with global inhibition makes it
an effective computational framework for grouping similar features and
segregating dissimilar ones in an image. We extract an algorithm from LEGION
dynamics and propose an adaptive scheme for grouping. We show results of the
algorithm to two-dimensional (2-D) and three-dimensional (3-D) (volume)
computerized topography (CT) and magnetic resonance imaging (MRI) medical-image
datasets. In addition, we compare our algorithm with other algorithms for medical
image segmentation, as well as with manual segmentation. LEGION's computational
and architectural properties make it a promising approach for real-time medical
image segmentation.
PMID- 10193700
TI - Time-frequency MEG-MUSIC algorithm.
AB - We propose a method that incorporates the time-frequency characteristics of
neural sources into magnetoencephalographic (MEG) source estimation. The method
is based on the multiple-signal-classification (MUSIC) algorithm and it
calculates a time--frequency matrix in which diagonal and off-diagonal terms are
the auto and crosstime--frequency distributions of multichannel MEG recordings,
respectively. The method averages this time-frequency matrix over the time-
frequency region of interest. The locations of neural sources are then estimated
by checking the orthogonality between the noise subspace of this averaged matrix
and the sensor lead field. Accordingly, the method allows us to estimate the
locations of neural sources from each time--frequency component. A computer
simulation was performed to test the validity of the proposed method, and the
results demonstrate its effectiveness.
PMID- 10193701
TI - Effect of electroacupuncture on the activities of tyrosine protein kinase in
subcellular fractions of activated T lymphocytes from the traumatized rats.
AB - The present study was to observe the dynamic changes of tyrosine protein kinase
(TPK) activity in subcellular fractions in the early stage of activation of T
lymphocytes from normal and traumatized rats, and the regulatory effect of
electroacupuncture (EA) stimulation on it. The results showed that the activities
of TPK in membranous and cytosolic fractions of activated T lymphocytes were
increased on second 5, and the peak was on scond 45 after ConA stimulation. Then
it was decreased gradually. Comparing with the control group, the activities of
TPK in membranous and cytosolic fractions of activated T lymphocytes from the
traumatized rats were inhibited in various degrees especially in membrane. EA of
"Zusanli"(ST-36) and "Lanwei"(Extra 33) points could enhance the activity of TPK
in subcellular fractions of activated T lymphocytes from the traumatized rats.
The results indicated that EA stimulation could prevent the inhibition of
activation of TPK induced by trauma stress, and contribute to transmembrane
signal transduction of T lymphocytes.
PMID- 10193702
TI - Analgesic effect of subcutaneous administration of oxygen-ozone. A blind study in
the rat on the modulation of the capsaicin-induced edema.
AB - The Authors have explored a new complementary approach, employed in the last 40
years for, among other uses, medical purposes: oxygen-ozone therapy. Anecdotal
works have highlighted interesting results obtained in disk herniation with
infiltration of paravertebral muscles with oxygen-ozone. To verify the existence
of a nociceptive effect and investigate a possible mechanism of action, an
experimental model of edema induction by subcutaneous capsaicin injection in the
rat paw was employed. Oxygen-ozone, in different concentrations (10 microg/ml, 20
microg/ml and 30 microg/ml) has been injected both ipsi- and contralaterally to
the paw 30 minutes before the administration of 50 microg capsaicin in 50 microl
of physiological solution. Results show that the contralateral injection of the
O2-O3 mixture modulates the edema response in the paw. Statistical significance,
for the 20 microg/ml mixture, lasts as far as 45 minutes after administration of
the capsaicin. No efficacy has been found for the 10 and 30 microg/ml
concentrations. An injection of the same quantity of gas in the ipsilateral paw
to the capsaicin-induced edema determines a worse edema than that observed in the
control group, as if the ozone mixture added its irritative effect to that of
capsaicin. It is interesting to note that the administration of oxygen alone
cause a greater edema than the oxygen-ozone mixture.
PMID- 10193703
TI - Estimation of the amount of telomere molecules in different human age groups and
the telomere increasing effect of acupuncture and shiatsu on St.36, using
synthesized basic units of the human telomere molecules as reference control
substances for the bi-digital O-ring test resonance phenomenon.
AB - It is well established that the telomeres at the ends of chromosomes are composed
of long arrays of (TTAGGG)n x (CCCTAA)n that form a nucleoprotein complex
required for the replication and protection of chromosome ends. Throughout the
cell cycle, telomeres also contain a protein component related to the proto
oncogene Myb that is known as TRF1 (telomere TTAGGG repeat binding factor 1) that
binds to the duplex array of TTAGGG repeats in the telomere. Previous studies
have shown that TRF1 appears to play a role in controlling the length of
telomeres by acting as an inhibitor of telomerase. The amount of each of the
TRF1(C-19) & TRF1(N-19) was identical to the amount of telomere of the same organ
of the same apparently normal individual. Using synthesized basic unit of TTAGGG,
as well as CCCTAA, as separate reference control substances for the Bi-Digital O
Ring Test of Resonance Phenomenon between 2 identical substances, we were able to
non-invasively measure the approximate amount of TTAGGG and CCCTAA units, in both
normal and cancerous human cells. We examined about 30 apparently normal subjects
(both Asian and Caucasian in both sex). The subjects' ages ranged from infancy to
76 years. Each subject was first examined using TTAGGG as a control substance and
then examined using CCCTAA as a control substance. The amount of telomere in
various cancer tissues are almost always higher than that of normal tissue of the
same organ. The measured amounts of both TTAGGG and CCCTAA were found to be in an
average of 1500-1600 ng for human fetus or infancy and decreased with the advance
of age in both sex with the exception of the heart, brain, eyes (retina), testes,
and ovaries, which usually remain at the level of the infant, or reduced very
little. Individuals in the same age group had a similar range of amounts of both
TTAGGG and CCCTAA in the same organ of the same individual, (except for those
with unusually low telomeres often had chronic degenerative diseases, and those
who had exceptionally high telomere levels often had excellent physical
conditions or mental acumen). The amounts of measured TTAGGG and CCCTAA molecules
before and after acupuncture on St. 36 in adenocarcinomas and small cell
carcinoma coexisting in the lung of a 54-yr.-old Asian male were: telomere in
adenocarcinoma decreased from 950 ng to 750 ng and telomere in small cell
carcinoma decreased from 770 ng to 600 ng. When the cancer treatment is
effective, the amount of telomere is reduced towards the value of the normal
internal organ. We found that acupuncture on St.36 on apparently normal subjects
increased the telomere levels up to a maximum of more than 2 times their telomere
levels prior to the treatment, depending on the method of treatment, but
frequently increases were between 60% to 100%. Strong Shiatsu performed on St. 36
produced a somewhat lesser effect than acupuncture. We also determined the
amounts of TTAGGG and CCCTAA molecules non-invasively in 3 mummified Egyptian
sisters from the 8th Century BC on exhibit at the Museo Egizio in Turin, Italy in
order to estimate their approximate ages (at the time of death). The amounts of
body telomere were 500 ng, 550 ng, and 750 ng. For the prehistoric Iceman (about
3350 B.C. to 3310 B.C) discovered in 1991 in the Italian Otzal Alps at about
3,200 meters altitude, estimated body telomere was about 400 ng and telomere in
brain and heart was 1600 ng, similar to that of a contemporary human being.
Although these studies are preliminary, the findings may have potential
applications not only in anti-aging, cancer treatments, and pathophysiology of
brain and heart, but also for the estimation of the difference in the ages of
cadavers studied in archeology and forensic medicine.
PMID- 10193704
TI - 30th Bethesda Conference: The Future of Academic Cardiology. Introduction.
PMID- 10193705
TI - 30th Bethesda Conference: The Future of Academic Cardiology. Task force 1:
clinical care.
PMID- 10193706
TI - 30th Bethesda Conference: The Future of Academic Cardiology. Task force 2:
research.
PMID- 10193707
TI - 30th Bethesda Conference: The Future of Academic Cardiology. Task force 3:
teaching.
PMID- 10193708
TI - 30th Bethesda Conference: The Future of Academic Cardiology. Task force 4:
faculty.
PMID- 10193709
TI - The Framingham Offspring Study: a commentary. 1980.
AB - Forty-three of 1,312 men aged 35 to 54 years in the Framingham Offspring Study
had clinically recognized coronary heart disease at the initial examination.
Twenty-six men in this group had previously had a myocardial infarction. Of 1,296
women in the same age range, only 11 had coronary disease and 3 a prior
myocardial infarction. The prevalence of coronary heart disease in men was
strongly associated with age, smoking, high density lipoprotein (HDL), low
density lipoprotein (LDL) and total cholesterol using univariate analyses. When
multivariate logistic regression analysis was used, age, smoking and HDL and LDL
cholesterol retained their significant association with coronary heart disease.
The total cholesterol/HDL cholesterol ratio was also strongly associated with
coronary heart disease in the multivariate analysis. It is concluded that both
HDL and LDL cholesterol are strongly and independently associated with the
prevalence of coronary heart disease, whereas the level of very low density
lipoprotein cholesterol makes no statistically significant independent
contribution.
PMID- 10193710
TI - A view from the millennium: the practice of cardiology circa 1950 and thereafter.
AB - The knowledge and treatment of cardiology as practiced circa 1950 is discussed as
abstracted from authoritative textbooks of that time and other sources. Advances
in treatment and diagnostic techniques since 1950 are presented. Dramatic changes
in cardiology have come at the expense of bedside cardiology which needs to be
balanced with the technology.
PMID- 10193711
TI - Drug-induced heart failure.
AB - Heart failure is a clinical syndrome that is predominantly caused by
cardiovascular disorders such as coronary heart disease and hypertension.
However, several classes of drugs may induce heart failure in patients without
concurrent cardiovascular disease or may precipitate the occurrence of heart
failure in patients with preexisting left ventricular impairment. We reviewed the
literature on drug-induced heart failure, using the MEDLINE database and lateral
references. Successively, we discuss the potential role in the occurrence of
heart failure of cytostatics, immunomodulating drugs, antidepressants, calcium
channel blocking agents, nonsteroidal anti-inflammatory drugs, antiarrhythmics,
beta-adrenoceptor blocking agents, anesthetics and some miscellaneous agents.
Drug-induced heart failure may play a role in only a minority of the patients
presenting with heart failure. Nevertheless, drug-induced heart failure should be
regarded as a potentially preventable cause of heart failure, although sometimes
other priorities do not offer therapeutic alternatives (e.g., anthracycline
induced cardiomyopathy). The awareness of clinicians of potential adverse effects
on cardiac performance by several classes of drugs, particularly in patients with
preexisting ventricular dysfunction, may contribute to timely diagnosis and
prevention of drug-induced heart failure.
PMID- 10193712
TI - Recent insight into therapy of congestive heart failure: focus on ACE inhibition
and angiotensin-II antagonism.
AB - One possible intervention to interrupt the deleterious effects of the renin
angiotensin system is suppression of angiotensin II (Ang II) formation by
inhibition of angiotensin-converting enzyme (ACE). However, ACE inhibition
incompletely suppresses Ang II formation and also leads to accumulation of
bradykinin. Angiotensin II type 1 (AT1) receptors are believed to promote the
known deleterious effects of Ang II. Therefore, AT1 receptor antagonists have
been recently introduced into therapy for hypertension and congestive heart
failure (CHF). Although there are significant differences between the effects of
AT1 receptor antagonists and ACE inhibitors including the unopposed stimulation
of angiotensin II type 2 (AT2) receptors by AT1 receptor antagonists, the
discussion of whether ACE inhibitors, AT1 receptor antagonists or the combination
of both are superior in the pharmacotherapy of CHF is still largely theoretical.
Accordingly, AT1 receptor antagonists are still investigational. Angiotensin
converting enzyme inhibitors remain first line therapy in patients with CHF due
to systolic dysfunction. However, in patients not able to tolerate ACE inhibitor
induced side effects, in particular cough, AT1 receptor antagonism is a good
alternative. In clinical practice, emphasis should be placed on increasing the
utilization of ACE inhibitors, as more than 50% of patients with CHF do not
receive ACE inhibitors. In addition, the majority of those on ACE inhibitors
receive doses lower than the dosage used in the large clinical trials. Although
not yet completely proved, it is likely that high doses of ACE inhibition are
superior to low doses with respect to prognosis and symptoms.
PMID- 10193713
TI - Dose-related beneficial long-term hemodynamic and clinical efficacy of irbesartan
in heart failure.
AB - OBJECTIVES: The primary purpose of this study was to determine the acute and long
term hemodynamic and clinical effects of irbesartan in patients with heart
failure. BACKGROUND: Inhibition of angiotensin II production by angiotensin
converting enzyme (ACE) inhibitors reduces morbidity and mortality in patients
with heart failure. Irbesartan is an orally active antagonist of the angiotensin
II AT1 receptor subtype with potential efficacy in heart failure. METHODS: Two
hundred eighteen patients with symptomatic heart failure (New York Heart
Association [NYHA] class II-IV) and left ventricular ejection fraction < or = 40%
participated in the study. Serial hemodynamic measurements were made over 24 h
following randomization to irbesartan 12.5 mg, 37.5 mg, 75 mg, 150 mg or placebo.
After the first dose of study medication, patients receiving placebo were
reallocated to one of the four irbesartan doses, treatment was continued for 12
weeks and hemodynamic measurements were repeated. RESULTS: Irbesartan induced
significant dose-related decreases in pulmonary capillary wedge pressure (average
change -5.9+/-0.9 mm Hg and -5.3+/-0.9 mm Hg for irbesartan 75 mg and 150 mg,
respectively) after 12 weeks of therapy without causing reflex tachycardia and
without increasing plasma norepinephrine. The neurohormonal effects of irbesartan
were highly variable and none of the changes was statistically significant. There
was a significant dose-related decrease in the percentage of patients
discontinuing study medication because of worsening heart failure. Irbesartan was
well tolerated without evidence of dose-related cough or azotemia. CONCLUSIONS:
Irbesartan, at once-daily doses of 75 mg and 150 mg, induced sustained
hemodynamic improvement and prevented worsening heart failure.
PMID- 10193714
TI - Left ventricular systolic and diastolic function after pericardiectomy in
patients with constrictive pericarditis: Doppler echocardiographic findings and
correlation with clinical status.
AB - OBJECTIVES: The study assessed changes in left ventricular systolic and diastolic
function after pericardiectomy in patients with constrictive pericarditis and
correlated postoperative Doppler echocardiographic findings with clinical status.
BACKGROUND: Despite the efficacy of pericardiectomy, some patients with
constrictive pericarditis fail to improve postoperatively. Data on serial
evaluation of systolic and diastolic function after pericardiectomy and its
relation to clinical status are not available. METHODS: From 1985 to 1995, a
total of 58 patients with constrictive pericarditis underwent pericardiectomy and
had at least one follow-up Doppler echocardiographic study with a respirometer:
23 patients had one examination within 3 months postoperatively, 19 had a study
within 3 months and another one more than 3 months postoperatively, and 16 had
one study more than 3 months postoperatively. RESULTS: In the early postoperative
period, diastolic function was normal in 17 patients (40.5%), restrictive in 17
(40.5%), and constrictive in 8 (19%). Among 19 patients who had serial Doppler
echocardiography, in 2 patients with restrictive physiology and 5 with
constrictive physiology the results had become normal, and 1 patient who had had
constrictive physiology had restrictive findings. In late follow-up, left
ventricular end-diastolic diameter increased compared with preoperative
measurement (p = 0.0009). Diastolic filling pattern at late follow-up was normal
in 20 patients (57%), restrictive in 12 (34%) and constrictive in 3 (9%). There
was a significant relationship between diastolic filling patterns and symptomatic
status (chi2 = 20.9, p < 0.0001). Patients with persistent abnormal diastolic
filling on Doppler echocardiography had had symptoms for a longer time
preoperatively than did patients with normal diastolic physiology (p = 0.0471).
CONCLUSIONS: Diastolic filling characteristics remain abnormal in a substantial
number of patients with constrictive pericarditis after pericardiectomy. These
abnormalities may resolve gradually but can persist. Diastolic filling
abnormalities after pericardiectomy correlate well with clinical symptoms and
tend to occur in patients who have had symptoms longer preoperatively. This
finding supports the recommendation that pericardiectomy be performed promptly in
symptomatic patients with constrictive pericarditis.
PMID- 10193715
TI - Mortality remains high for outpatient transplant candidates with prolonged (>6
months) waiting list time.
AB - OBJECTIVES: The study aimed to determine the risk of death or urgent transplant
for patients who survived an initial 6 months on the outpatient heart transplant
waiting list when criteria emphasizing reduced peak oxygen consumption are used
for transplant candidate selection. BACKGROUND: Waiting time is a key criterion
for heart donor allocation. A recent single-center investigation described
decreasing survival benefit from transplant for patients who survived an initial
6 months on the outpatient waiting list. METHODS: Kaplan-Meier survival analyses
were performed for 80 patients from the Hospital of the University of
Pennsylvania (HUP) listed from July 1986 to January 1991, and 132 patients from
Columbia-Presbyterian Medical Center (CPMC) listed from September 1993 to
September 1995. Survival from the time of outpatient listing for the entire group
(ALL) was compared to subsequent survival from 6 months onward for those patients
who survived the initial 6 months after placement on the outpatient list (6M).
Both urgent transplant and left ventricular assist device implantation were
considered equivalent to death; elective transplant was censored. RESULTS
Survival for 6M was not significantly better than ALL at HUP (subsequent 12
months: 60+/-7 vs. 60+/-6% [mean+/-SD]; p = 0.89) nor at CPMC (subsequent 12
months: 60+/-6 vs. 48+/-5%; p = 0.35). Survival for 6M at both centers was
substantially lower than survival following transplant from the outpatient list
in the United States in 1995. CONCLUSIONS: When high-risk patients are selected
for nonurgent transplant listing, mortality remains high, even among those who
survive the initial six months after listing. Time accrued on the waiting list
remains an appropriate criterion for donor allocation.
PMID- 10193716
TI - Cerebral metabolic abnormalities in congestive heart failure detected by proton
magnetic resonance spectroscopy.
AB - OBJECTIVES: Using proton magnetic resonance spectroscopy, we investigated
cerebral metabolism and its determinants in congestive heart failure (CHF), and
the effects of cardiac transplantation on these measurements. BACKGROUND: Few
data are available about cerebral metabolism in CHF. METHODS: Fifty patients with
CHF (ejection fraction < or = 35%) and 20 healthy volunteers were included for
this study. Of the patients, 10 patients underwent heart transplantation. All
subjects performed symptom-limited bicycle exercise test. Proton magnetic
resonance spectroscopy (1H MRS) was obtained from localized regions (8 to 10 ml)
of occipital gray matter (OGM) and parietal white matter (PWM). Absolute levels
of the metabolites (N-acetylaspartate, creatine, choline, myo-inositol) were
calculated. RESULTS: In PWM only creatine level was significantly lower in CHF
than in control subjects, but in OGM all four metabolite levels were decreased in
CHF. The creatine level was independently correlated with half-recovery time and
duration of heart failure symptoms in PWM (r = -0.56, p < 0.05), and with peak
oxygen consumption and serum sodium concentration in OGM (r = 0.58, p < 0.05).
Cerebral metabolic abnormalities were improved after successful cardiac
transplantation. CONCLUSIONS: This study shows that cerebral metabolism is
abnormally deranged in advanced CHF and it may serve as a potential marker of the
disease severity.
PMID- 10193717
TI - Prognostic value of heart rate variability for sudden death and major arrhythmic
events in patients with idiopathic dilated cardiomyopathy.
AB - OBJECTIVE: This study was designed to evaluate the prognostic value of heart rate
variability for sudden death, resuscitated ventricular fibrillation or sustained
ventricular tachycardia in patients with idiopathic dilated cardiomyopathy.
BACKGROUND: Previous studies have shown that heart rate variability could predict
arrhythmic events and sudden death in postinfarction patients, but the prognostic
value of heart rate variability for arrhythmic events or sudden death in patients
with idiopathic dilated cardiomyopathy has not been established. METHODS: Time
and frequency domain analysis of heart rate variability on 24-h
electrocardiographic (ECG) recording was assessed in 116 patients with idiopathic
dilated cardiomyopathy (91 men, aged 51+/-12 years, left ventricular ejection
fraction 34+/-12%). RESULTS: Mean follow-up (+/-SD) was 53+/-39 months. Sixteen
patients reached one of the defined study end-points (sudden death, resuscitated
ventricular fibrillation or sustained ventricular tachycardia) during follow-up.
Using multivariate analysis, only reduced standard deviation of all normal-to
normal intervals (SDNN) (p = 0.02) and ventricular tachycardia during 24-h ECG
recording (p = 0.02) predicted sudden death and/or arrhythmic events. For SDNN, a
cutoff level of 100 ms seemed the best for the risk stratification. CONCLUSIONS:
Decrease in heart rate variability is an independent predictor of arrhythmic
events and sudden death in idiopathic dilated cardiomyopathy, whether the
mechanism of sudden death is ventricular tachyarrhythmia or not.
PMID- 10193718
TI - Relation between mode of pacing and long-term survival in the very elderly.
AB - OBJECTIVES: This study analyzes the relationship between pacing mode and long
term survival in a large group of very elderly patients (> or = 80 years old).
BACKGROUND: The relationship between pacing mode and long-term survival is not
clear. Because the number of very elderly who are candidates for pacing is
increasing, issues related to pacemaker (PM) use in the elderly have important
clinical and economic implications. METHODS: We retrospectively reviewed 432
patients (mean age, 84.5+/-3.9 years) who received their initial PM (ventricular
in 310 and dual chamber in 122) between 1980 and 1992. Follow-up was complete
(3.5+/-2.6 years). Observed survival was estimated by the Kaplan-Meier method.
Age- and gender-matched cohorts from the Minnesota population were used for
expected survival. Log-rank test and Cox regression hazard model were used for
univariate and multivariate analyses. RESULTS: Patients with ventricular PMs
appeared to have poor overall survival compared with those with dual-chamber PMs.
Observed survival after PM implantation in high grade atrioventricular block
(AVB) patients was significantly worse than expected survival of the age- and
gender-matched population (p < 0.0001), whereas observed survival of patients
with sinus node dysfunction was not significantly different from expected
survival of the matched population (p = 0.413). By univariate analysis,
ventricular pacing in patients with AVB appeared to be associated with poor
survival compared with dual-chamber pacing (hazard ratio [HR] 2.08; 95%
confidence interval [CI] 1.33 to 3.33). After multivariate analysis, this
difference was no longer significant (HR 1.41; 95% CI 0.88 to 2.27). Independent
predictors of all-cause mortality were number of comorbid illnesses, New York
Heart Association functional class, left ventricular depression and older age at
implant. Pacing mode was not an independent predictor of overall survival. Older
age at implantation, diabetes mellitus, dementia, history of paroxysmal atrial
fibrillation and earlier year of implantation were independent predictors of
ventricular pacemaker selection. CONCLUSIONS: After PM implantation, long-term
survival among very elderly patients was not affected by pacing mode after
correction of baseline differences. Selection bias was present in pacing mode in
the very elderly, with ventricular pacing selected for sicker and older patients,
perhaps partly explaining the apparent "beneficial impact on survival" observed
with dual-chamber pacing.
PMID- 10193719
TI - Defibrillation-guided radiofrequency ablation of atrial fibrillation secondary to
an atrial focus.
AB - OBJECTIVES: Our aim was to evaluate a potential focal source of atrial
fibrillation (AF) by unmasking spontaneous early reinitiation of AF after
transvenous atrial defibrillation (TADF), and to describe a method of using
repeated TADF to map and ablate the focus. BACKGROUND: Atrial fibrillation may
develop secondary to a rapidly discharging atrial focus that the atria cannot
follow synchronously, with suppression of the focus once AF establishes. Focus
mapping and radiofrequency (RF) ablation may be curative but is limited if the
patient is in AF or if the focus is quiescent. Early reinitiation of AF has been
observed following defibrillation, which might have a focal mechanism. METHODS:
We performed TADF in patients with drug-refractory lone AF using electrodes in
the right atrium (RA) and the coronary sinus. When reproducible early
reinitiation of AF within 2 min after TADF was observed that exhibited a
potential focal mechanism, both mapping and RF ablation were performed to
suppress AF reinitiation. Clinical and ambulatory ECG monitoring was used to
assess AF recurrence. RESULTS: A total of 44 lone AF patients (40 men, 4 women;
32 persistent, 12 paroxysmal AF) with a mean age of 58+/-13 years underwent TADF.
Sixteen patients had early reinitiation of AF after TADF, nine (20%; 5
paroxysmal) exhibited a pattern of focal reinitiation. Earliest atrial activation
was mapped to the right superior (n = 4) and the left superior (n = 3) pulmonary
vein, just inside the orifice, in the seven patients who underwent further study.
At the onset of AF reinitiation, the site of earliest activation was 86+/-38 ms
ahead of the RA reference electrogram. The atrial activities from this site were
fragmented and exhibited progressive cycle-length shortening with decremental
conduction to the rest of the atrium until AF reinitiated. Radiofrequency
ablation at the earliest activation site resulted in suppression of AF
reinitiation despite pace-inducibility. Improved clinical outcome was observed
over 8+/-4 months' follow-up. CONCLUSIONS: Transvenous atrial defibrillation can
help to unmask, map, and ablate a potential atrial focus in patients with
paroxysmal and persistent AF. A consistent atrial focus is the cause of early
reinitiation of AF in 20% of patients with lone AF, and these patients may
benefit from this technique.
PMID- 10193720
TI - Effects of paroxetine hydrochloride, a selective serotonin reuptake inhibitor, on
refractory vasovagal syncope: a randomized, double-blind, placebo-controlled
study.
AB - OBJECTIVES: The purpose of the study was to determine whether the well tolerated
serotonin reuptake inhibitor paroxetine hydrochloride could prevent vasovagal
syncope in patients resistant to or intolerant of previous traditional therapies.
BACKGROUND: Serotonergic mechanisms play a major role in the processes leading to
neurocardiogenic vasovagal syncope, and serotonin reuptake inhibitors have been
reported to be effective in preventing refractory syncope. METHODS: Sixty-eight
consecutive patients (26 men and 42 women, mean age 44.7+/-16.5 years) with
recurrent syncope and positive head-up tilt test and in whom standard therapies
with beta-adrenergic blocking agents, vagolytic, negative inotropic or mineral
corticoid agents were ineffectual or poorly tolerated were referred for study.
Patients randomly received either paroxetine at 20 mg once a day or a placebo. A
head-up tilt test was then reperformed after one month of treatment, and the
clinical effect was noted over a mean follow-up of 25.4+/-7.9 months. RESULTS:
The response rates (negative tilt test) after one month of treatment were 61.8%
versus 38.2% (p < 0.001) in the paroxetine and placebo groups, respectively.
During follow-up spontaneous syncope was reported in six patients (17.6%) in the
paroxetine group as compared to 18 patients (52.9%) in the placebo group (p <
0.0001). Only one patient (2.9%) asked to be discontinued from the drug for
severe side effects. CONCLUSIONS: Paroxetine was found to significantly improve
the symptoms of patients with vasovagal syncope unresponsive to or intolerant of
traditional medications and was well tolerated by patients.
PMID- 10193721
TI - Down-regulation of L-type calcium channel and sarcoplasmic reticular Ca(2+)
ATPase mRNA in human atrial fibrillation without significant change in the mRNA
of ryanodine receptor, calsequestrin and phospholamban: an insight into the
mechanism of atrial electrical remodeling.
AB - OBJECTIVES: We investigated the gene expression of calcium-handling genes
including L-type calcium channel, sarcoplasmic reticular calcium adenosine
triphosphatase (Ca(2+)-ATPase), ryanodine receptor, calsequestrin and
phospholamban in human atrial fibrillation. BACKGROUND: Recent studies have
demonstrated that atrial electrical remodeling in atrial fibrillation is
associated with intracellular calcium overload. However, the changes of calcium
handling proteins remain unclear. METHODS: A total of 34 patients undergoing open
heart surgery were included. Atrial tissue was obtained from the right atrial
free wall, right atrial appendage, left atrial free wall and left atrial
appendage, respectively. The messenger ribonucleic acid (mRNA) amount of the
genes was measured by reverse transcription-polymerase chain reaction and
normalized to the mRNA levels of glyceraldehyde 3-phosphate dehydrogenase.
RESULTS: The mRNA of L-type calcium channel and of Ca(2+)-ATPase was
significantly decreased in patients with persistent atrial fibrillation for more
than 3 months (0.36+/-0.26 vs. 0.90+/-0.88 for L-type calcium channel; 0.69+/
0.42 vs. 1.21+/-0.68 for Ca(2+)-ATPase; both p < 0.05, all data in arbitrary
unit). We further demonstrated that there was no spatial dispersion of the gene
expression among the four atrial tissue sampling sites. Age, gender and
underlying cardiac disease had no significant effects on the gene expression. In
contrast, the mRNA levels of ryanodine receptor, calsequestrin and phospholamban
showed no significant change in atrial fibrillation. CONCLUSIONS: L-type calcium
channel and the sarcoplasmic reticular Ca(2+)-ATPase gene were down-regulated in
atrial fibrillation. These changes may be a consequence of, as well as a
contributory factor for, atrial fibrillation.
PMID- 10193722
TI - Percutaneous revascularization of atherosclerotic obstruction of aortic arch
vessels.
AB - OBJECTIVES: To compare stenting of aortic arch vessel obstruction with surgical
therapy and to establish recommendations for treatment. BACKGROUND: Though
surgery has been considered to be the procedure of choice for subclavian and
brachiocephalic obstruction, little work has been done to compare it with
stenting. METHODS: Eighteen patients with symptomatic aortic arch vessel stenosis
or occlusion were treated with stenting, followed by periodic clinical follow-up
and noninvasive arterial Doppler studies. Data were compared with the results as
shown in a systematic review of a published series of surgery and stenting
procedures which included comparison of technical success, complications,
mortality and patency. RESULTS: Primary success in our series was 100% with
improvement in mean stenosis from 84+/-11% to 1+/-5% and mean arm systolic blood
pressure difference from 44+/-16 mm Hg to 3+/-3 mm Hg. There were no major
complications (death, stroke, TIA, stent thrombosis or myocardial infarction). At
follow-up (mean 17 months), all patients were asymptomatic with 100% primary
patency. Literature review demonstrates equivalent patency and complications in
the other published series of stenting. In contrast, there was a similar patency
but overall incidence of stroke of 3+/-4% and death of 2+/-2% in the published
surgical series. CONCLUSIONS: Subclavian or brachiocephalic artery obstruction
can be effectively treated by primary stenting or surgery. Comparison of stenting
and the surgical experience demonstrates equal effectiveness but fewer
complications and suggests that stenting should be considered as first line
therapy for subclavian or brachiocephalic obstruction.
PMID- 10193723
TI - The times they are a-changin'....
PMID- 10193724
TI - Antithrombin activity during the period of percutaneous coronary
revascularization: relation to heparin use, thrombotic complications and
restenosis.
AB - OBJECTIVES: This study evaluated changes in antithrombin (AT) activity around the
time of percutaneous transluminal coronary revascularization (PTCR) with
unfractionated heparin anticoagulation and the effects these changes had on major
thrombotic complications of PTCR. BACKGROUND: Heparin is used during PTCR to
prevent thrombosis. However, heparin, a cofactor for AT, causes AT activity to
fall. AT activity <70% is associated with thrombosis. There is a prothrombotic
state after heparin discontinuation that has not been well explained. METHODS:
Antithrombin activity was sampled at the start and end of PTCR and the next two
mornings in 250 consecutive patients. We recorded occurrence of major thrombotic
events, defined as 1) major thrombotic complications of PTCR; 2) major in-lab
thrombus formation; or 3) subacute occlusion. Discriminant analysis was employed
to evaluate the relationship of AT activity to these events. Change in AT
activity and its relationship to heparin was evaluated. Evidence of restenosis at
six months was obtained. RESULTS: There were 14 major thrombotic events.
Antithrombin activity <70% was strongly (p = 0.006) associated with these events.
The AT activity fell significantly through the morning after PTCR when 21% of
patients had AT activity <70%; AT activity did not normalize until >20 h after
heparin discontinuation. Pre-PTCR use of heparin led to lower AT activity in
proportion to duration of heparin use. There was no relationship between AT
activity and restenosis. CONCLUSIONS: Low AT activity may contribute to major
thrombotic complications of PTCR. The way heparin is used before and after PTCR
is important to development of low AT activity.
PMID- 10193725
TI - Primary angioplasty for the treatment of acute myocardial infarction: experience
at two community hospitals without cardiac surgery.
AB - OBJECTIVES: We sought to establish the safety and efficacy of primary
percutaneous transluminal coronary angioplasty in patients with acute myocardial
infarction (AMI) at two community hospitals without on-site cardiac surgery.
BACKGROUND: Though randomized studies indicate that primary angioplasty in AMI
may result in superior outcomes compared with fibrinolytic therapy, the
performance of primary angioplasty at hospitals without cardiac surgery is
debated. METHODS: Three experienced operators performed 506 consecutive immediate
coronary angiograms with primary angioplasty when appropriate in patients with
suspected AMI at two community hospitals without cardiac surgery, following
established rigorous program criteria. RESULTS: Clinical high risk predictors
(Killip class 3 or 4, age > or = 75 years, anterior AMI, out-of-hospital
ventricular fibrillation) and/or angiographic high risk predictors (left main or
three-vessel disease or ejection fraction <45%) were present in 69.6%.
Angioplasty was performed in 66.2%, with a median time from emergency department
presentation to first angiogram of 94 min and a procedural success rate of 94.3%.
The in-hospital mortality for the entire study population was 5.3%. Of those
without initial cardiogenic shock, the in-hospital mortality was 3.0%. Of 300
patients who were discharged after primary angioplasty, only four died within the
first 6 months, with 97.7% follow-up. No patient died or needed emergent
aortocoronary bypass surgery because of new myocardial jeopardy caused by a
complication of the cardiac catheterization or angioplasty procedure.
CONCLUSIONS: Immediate coronary angiography with primary angioplasty when
appropriate in patients with AMI can be performed safely and effectively in
community hospitals without on-site cardiac surgery when rigorous program
criteria are established.
PMID- 10193726
TI - Guidelines for surgical standby for coronary angioplasty: should they be changed?
PMID- 10193727
TI - The importance of proteinuria as a determinant of mortality following
percutaneous coronary revascularization in diabetics.
AB - OBJECTIVES: The aims of this study were to compare mortality and clinical events
following percutaneous coronary intervention (PCI) between nondiabetics and
diabetics with and without proteinuria. BACKGROUND: Diabetics have increased
rates of late myocardial infarction, repeat revascularization and mortality when
compared with nondiabetics following PCI. Proteinuria is a marker for diabetic
nephropathy and potentially a surrogate marker for advanced atherosclerosis. It
is unknown if proteinuria is a predictor of outcome in diabetics following PCI.
METHODS: We performed an observational study of 2,784 patients who underwent PCI
at the Cleveland Clinic between January 1993 and December 1995. There were 2,247
nondiabetics and 537 diabetics with urinalysis and follow-up data available
(proteinuria n = 217, nonproteinuria n = 320). The diabetic proteinuria group was
further prospectively stratified into low concentration (n = 182) and high
concentration (n = 35). The end points were all-cause mortality and the composite
end point of death, nonfatal myocardial infarction (MI) and need for
revascularization. RESULTS: The mean follow-up time was 20.2 months. The two-year
mortality rate was 7.3% and 13.5% for nondiabetics and diabetics, respectively (p
< 0.001). The two-year mortality rate was 9.1% and 20.3% for the nonproteinuria
and proteinuria groups, respectively (p < 0.001). There was a graded increase in
mortality comparing the diabetic group. The two-year mortality rate was 9.1%,
16.2% and 43.1% for the nonproteinuria, low concentration and high concentration
groups, respectively (p < 0.001). The difference in survival between the
nondiabetic and nonproteinuric diabetics was not significant (p = 0.8).
CONCLUSIONS: The presence of proteinuria is the key determinant of risk following
PCI for diabetics. Diabetics without evidence of proteinuria have similar
survival compared with nondiabetics.
PMID- 10193728
TI - Comparing physician-specific two-year patient outcomes after coronary
angiography: methodologic issues and results.
AB - OBJECTIVES: We sought to evaluate methodologies to compare physician-related long
term patient outcomes appropriately. BACKGROUND: Evaluation of physicians on the
basis of short-term patient outcome is becoming widely practiced. These analyses
fail to consider the importance of long-term outcome, and methods appropriate to
such an analysis are poorly defined. METHODS: All patients undergoing coronary
angiography between 1992 and 1994 who received all of their cardiac care at our
institution were followed for 27+/-13 months (mean+/-SD). Patients (n = 754) were
cared for by one or more of 17 staff physicians. Risk-adjusted models were
developed for four candidate clinical end points and cost. Physicians were then
evaluated for each outcome measure. RESULTS: Of the clinical end points, death
could be modeled most accurately (c-statistic = 0.83). The c-statistics for other
end points ranged from 0.63 to 0.70. Physicians with outcomes statistically
different (p < 0.05) from other physicians were identified more commonly than
would be expected from the play of chance (p = 0.005). However, improvement in
the c-statistics by the addition of physician identifiers was very modest.
Physician's evaluations by the four measures of clinical outcome were variably
correlated (r = .00 to .85). Graphic display of clinical and cost results for
each physician did identify certain physicians who might be judged to provide
more cost-effective care than others. CONCLUSIONS: Although comparisons of groups
of physicians on the basis of long-term patient outcomes may have merit,
individual physician-to-physician comparisons will be more difficult, owing to 1)
multiple physicians contributing care to individual patients; 2) the poor
predictive capacity of models other than that for survival; and 3) the modest
apparent impact of differences in physician providers on long-term patient
outcome. With these caveats in mind, modeling to compare patient outcomes of
individual physicians with homogeneous patient populations or to identify gross
outliers (good or bad) may be practicable in some patient-care systems, but may
be inappropriate in others.
PMID- 10193729
TI - Inhibition of thrombin generation by simvastatin and lack of additive effects of
aspirin in patients with marked hypercholesterolemia.
AB - OBJECTIVES: To assess the effects of aspirin compared with simvastatin on
thrombin generation in hypercholesterolemic men, and to establish whether the
reduction of elevated blood cholesterol by simvastatin would affect the action of
aspirin on thrombin formation. BACKGROUND: Aspirin inhibits thrombin formation,
but its performance is blunted in hypercholesterolemia. By virtue of altering
lipid profile, statins could be expected to influence thrombin generation.
METHODS: Thirty-three men, aged 34 to 61 years, with minimal or no clinical
symptoms, serum total cholesterol >6.5 mmol/liter and serum triglycerides <4.6
mmol/liter, completed the study consisting of three treatment phases. First, they
received 300 mg of aspirin daily for two weeks (phase I), which was then replaced
by simvastatin at the average dose of 24 mg/d for three months (phase II). In
phase III, aspirin, 300 mg/day, was added for two weeks to simvastatin, the dose
of which remained unchanged. Thrombin generation was assessed: 1) in vivo, by
measuring levels of fibrinopeptide A (FPA) and prothrombin fragment 1+2 (F1+2) in
venous blood; and 2) ex vivo, by monitoring the rates of increase of FPA and F1+2
in blood emerging from standardized skin incisions of a forearm. A mathematical
model was used to describe the kinetics of thrombin formation at the site of
microvascular injury. RESULTS: Two-week treatment with aspirin had no effect on
thrombin markers in vivo, while ex vivo it depressed the total amount of thrombin
formed, though not the reaction rate. After simvastatin treatment, serum
cholesterol decreased by 31% and LDL cholesterol by 42%, while thrombin
generation became markedly depressed. In venous blood, FPA was significantly
reduced. Concomitantly, the initial thrombin concentration and total amount of
thrombin generated decreased significantly. Addition of aspirin to simvastatin
(phase III) had no further effect on any of these parameters. CONCLUSIONS: In men
with hypercholesterolemia, lowering serum cholesterol level by a three-month
simvastatin treatment is accompanied by a marked reduction of thrombin generation
both at basal conditions in venous blood and after activation of hemostasis by
microvascular injury. Once blood cholesterol became reduced, adding aspirin to
simvastatin did not enhance dampening of thrombin formation.
PMID- 10193730
TI - Pravastatin therapy in hyperlipidemia: effects on thrombus formation and the
systemic hemostatic profile.
AB - OBJECTIVES: The study sought to determine the effects of lipid-lowering with
pravastatin on the systemic fibrinolytic profile and on thrombus formation under
dynamic flow conditions. BACKGROUND: Lowering cholesterol (C) decreases clinical
events in coronary artery disease (CAD) patients, but an analysis of the effects
of lipid-lowering on the entire hemostatic and thrombotic profile has not been
conducted. METHODS: We prospectively studied 93 stable patients with untreated
low-density lipoprotein cholesterol (LDL-C) >145 mg/dl. The CAD patients received
pravastatin, and non-CAD patients were randomized to pravastatin versus placebo
(double-blind). Thrombus formation upon an injured vascular surface was assessed
in a substudy of 40 patients with a previously validated ex vivo perfusion
chamber system. Systemic hemostatic markers and thrombus formation were evaluated
at baseline, three and six months. RESULTS: Placebo produced no changes in either
the lipid profile, any of the hemostatic markers, or the ex vivo thrombus
formation. Both pravastatin groups (CAD and non-CAD) showed decreased LDL-C by
30% within 6 weeks (188 to 126 mg/dl, p < 0.001 vs. baseline), and decreased
plasminogen activator inhibitor-1 at 3- and 6-month follow-up compared to
baseline (15% to 18% decrease at 3 months and 21% to 23% at 6 months). For the
tissue plasminogen activator antigen, CAD and non-CAD groups showed significant
decreases at 6 months compared to baseline (10% and 13%, respectively). No
significant changes were observed with treatment in d-dimer, fibrinopeptide A,
prothrombin fragment F1.2, factor VIIa, von Willebrand factor, or C-reactive
protein. Fibrinogen levels were significantly increased at 6 months compared to
baseline, though still below the upper normal limit. In the perfusion chamber
substudy, there was a decrease in thrombus area in non-CAD patients treated with
pravastatin at both 3 and 6 months compared to baseline (by 21% and 34%,
respectively). The CAD patients showed decreases in thrombus formation by 13% at
3 months, and by 16% at 6 months. The change in LDL-C- correlated modestly with
the change in thrombus formation (r = 0.49; p < 0.01). CONCLUSIONS: Pravastatin
therapy significantly decreased thrombus formation and improved the fibrinolytic
profile in patients with and without CAD. These early effects may, in part,
explain the benefit rendered in primary and secondary prevention of CAD.
PMID- 10193731
TI - The anti-thrombotic effects of statins.
PMID- 10193732
TI - Atherosclerosis of the ascending aorta is an independent predictor of long-term
neurologic events and mortality.
AB - OBJECTIVES: This study was undertaken to determine whether atherosclerosis of the
ascending aorta is a predictor of long-term neurologic events and mortality.
BACKGROUND: Atherosclerosis of the thoracic aorta has been recently considered a
significant predictor of neurologic events and peripheral embolism, but not of
long-term mortality. METHODS: Long-term follow-up (a total of 5,859 person-years)
was conducted of 1,957 consecutive patients > or =50 years old who underwent
cardiac surgery. Atherosclerosis of the ascending aorta was assessed
intraoperatively (epiaortic ultrasound) and patients were divided into four
groups according to severity (normal, mild, moderate or severe). Carotid artery
disease was evaluated (carotid ultrasound) in 1,467 (75%) patients. Cox
proportional-hazards regression analysis was performed to assess the independent
effect of predictors on neurologic events and mortality. RESULTS: A total of 491
events occurred in 472 patients (neurologic events 92, all-cause mortality 399).
Independent predictors of long-term neurologic events were: hypertension (p =
0.009), ascending aorta atherosclerosis (p = 0.011) and diabetes mellitus (p =
0.015). The independent predictors of mortality were advanced age (p < 0.0001),
left ventricular dysfunction (p < 0.0001), ascending aorta atherosclerosis (p <
0.0001), hypertension (p = 0.0001) and diabetes mellitus (p = 0.0002). There was
>1.5-fold increase in the incidence of both neurologic events and mortality as
the severity of atherosclerosis increased from normal-mild to moderate, and a
greater than threefold increase in the incidence of both as the severity of
atherosclerosis increased from normal-mild to severe. CONCLUSIONS:
Atherosclerosis of the ascending aorta is an independent predictor of long-term
neurologic events and mortality. These results provide additional evidence that
in addition to being a direct cause of cerebral atheroembolism, an
atherosclerotic ascending aorta may be a marker of generalized atherosclerosis
and thus of increased morbidity and mortality.
PMID- 10193733
TI - Atherosclerosis of the thoracic aorta and aortic debris as a marker of poor
prognosis: benefit of oral anticoagulants.
AB - OBJECTIVES: Our aim was to confirm the poor prognosis related to thoracic aortic
plaques, in particular aortic debris, diagnosed by transesophageal
echocardiography (TEE) and to evaluate patients' prognosis as a function of the
antithrombotic treatment. BACKGROUND: Aortic atheroma (AA) has been widely
studied. However, it is still not known which antithrombotic treatment should be
adopted in this disease. METHODS: Patients referred for TEE and diagnosed with AA
were followed. All thromboembolic events and deaths were recorded during a follow
up of 22+/-10 months. The antithrombotic treatment to be adopted was left to the
discretion of the practitioner in charge of the patient. RESULTS: Aortic atheroma
was found in 12% of all TEE performed and in 27.5% of TEE performed for stroke.
This prevalence was higher when no other etiology existed to explain the stroke
(p < 0.001). During follow-up, an end point occurred in 22.5% of patients. The
more severe the AA the greater the incidence of events (p = 0.007). A higher
mortality rate is shown in patients with aortic debris (p = 0.049). Compared with
those treated with oral anticoagulants, patients with aortic plaques >4 mm thick
treated with antiplatelets had more embolic events and combined events (p = 0.01
and p = 0.007, relative risk [RR] = 5.9, 95% confidence interval [CI] = 1.4 to
15, respectively); patients with aortic debris had more combined events and a
higher mortality rate (p = 0.001, RR = 7.1, 95% CI = 1.2 to 19 and p = 0.019, RR
= 9.1, 95% CI = 1.2 to 25, respectively). CONCLUSIONS: We confirm the high
incidence of vascular events and deaths in patients with AA. We have
demonstrated, for the first time in this condition, a better outcome among
patients treated with oral anticoagulants versus antiplatelets.
PMID- 10193734
TI - Comparison of pulmonary uptake with transient cavity dilation after exercise
thallium-201 perfusion imaging.
AB - OBJECTIVES: The purpose of the study was to evaluate the relationship between
elevated lung/heart ratio (LHR) and transient ischemic dilation (TID) after
stress thallium-201 myocardial perfusion imaging and to provide further insight
into the mechanism of cavity dilation. BACKGROUND: Because both LHR and TID have
been identified as adjunctive markers of severe coronary disease they should be
found in the same patients. Although the mechanism of LHR has been defined, that
of transient dilation has not. METHODS: We identified 4,618 consecutive patients
undergoing maximal exercise perfusion imaging with thallium-201. Lung/heart ratio
and a dilation index were derived and compared to each other and to relevant
clinical parameters. RESULTS: There was a very weak relationship between the LHR
and dilation index (r = 0.15, p < 0.001). Defining a dilation index > or =1.10
and LHR > or =50% as abnormal revealed that 322 of the patients (7%) had TID
only, 351 (7.8%) had LHR only and 40 (0.9%) had both. When compared to patients
without these findings both TID and LHR had higher thallium stress defect and
redistribution scores. When comparing subjects who had elevated LHR uptake to
those who had TID, it was found that those with LHR were more likely to have had
prior myocardial infarction (MI) (29% vs. 9%), coronary artery bypass grafting
(22% vs. 8%), lower ejection fraction (34+/-17% vs. 55+/-11%) and had more
evidence of ischemia based on thallium stress defect and redistribution scores.
However, patients with cavity dilation had a higher frequency of positive
electrocardiographic response (31% vs. 19%) despite lower scintigraphic markers.
CONCLUSIONS: Although pulmonary uptake and transient cavity dilation have both
been associated with severe coronary disease, they have a very weak correlation,
which, in combination with the different clinical parameters associated with
each, suggests that they represent different pathophysiologic responses to
exercise-induced ischemia. Our data support the hypothesis that TID represents
transient subendocardial ischemia rather than physical dilation from increased
end-diastolic pressure.
PMID- 10193735
TI - Blood flow-metabolism imaging with positron emission tomography in patients with
diabetes mellitus for the assessment of reversible left ventricular contractile
dysfunction.
AB - OBJECTIVES: The purpose of this study was to evaluate the predictive accuracy of
positron emission tomography (PET) blood flow-F-18 fluorodeoxyglucose (FDG)
imaging in coronary artery disease (CAD) patients with diabetes mellitus (DM).
BACKGROUND: Positron emission tomography accurately predicts the
postrevascularization improvement in left ventricular dysfunction in unselected
patients with CAD. In diabetic patients, however, poor myocardial glucose
utilization may limit the accuracy of the approach. METHODS: Forty patients (64+/
10 years old; 19 with DM = group I; 21 without DM = group II) with reduced left
ventricular ejection fraction (LVEF = 29+/-6%) were studied with N-13 ammonia and
FDG PET before coronary revascularization. Studies were performed after
intravenous injection of regular insulin (group I) or oral glucose administration
(group II). Blood flow-FDG mismatches and matches were identified by polar map
analysis in the three vascular territories of the left anterior descending, left
circumflex and right coronary artery. Wall motion and LVEF were assessed by two
dimensional echocardiography before and 158+/-123 days after revascularization.
RESULTS: Of 107 vascular territories analyzed, 46 were classified as mismatch, 29
as match and 32 as normal. The FDG image quality, assessed by F-18 myocardium to
blood pool activity ratios, and the predictive accuracy were similar in both
groups; presence of a blood flow/FDG mismatch had a sensitivity of 92% (group I)
and 94% (group II) and a specificity of 85% (group I) and 79% (group II) for an
improvement in regional left ventricular function. A postrevascularization
improvement in global left ventricular function was related to the extent of
blood flow/FDG mismatch; LVEF increased from 30+/-7% to 35+/-7% (p = 0.017) in
patients with one mismatch and from 27+/-4% to 41+/-7% (p < 0.001) in those with
two mismatches. CONCLUSIONS: The predictive accuracy of blood flow/FDG imaging is
maintained in patients with DM when a clinically acceptable study protocol, which
guarantees good FDG image quality, is used. The extent of a blood flow/metabolism
mismatch is correlated with the magnitude of the postrevascularization
improvement in global left ventricular function.
PMID- 10193736
TI - Phasic coronary flow pattern and flow reserve in patients with left bundle branch
block and normal coronary arteries.
AB - OBJECTIVES: The purpose of this study was to determine whether scintigraphic
myocardial perfusion defects in patients with left bundle branch block (LBBB) and
normal coronary arteries are related to abnormalities in coronary flow velocity
pattern and/or coronary flow reserve. BACKGROUND: Septal or anteroseptal defects
on exercise myocardial perfusion scintigraphy are common in patients with LBBB
and normal coronary arteries. METHODS: Thirteen patients (7 men, age 61+/-8
years) with LBBB and normal coronary arteries underwent stress thallium-201
scintigraphy and cardiac catheterization. In all patients and in 11 control
subjects coronary blood flow parameters were calculated from Doppler measurements
of flow velocity in the left anterior descending coronary artery (LAD) before and
after adenosine administration. RESULTS: The time to maximum peak diastolic flow
velocity was significantly longer both for the seven patients with (134+/-19 ms)
and for the six without (136+/-7 ms) exercise perfusion defects than for controls
(105+/-12 ms, p < 0.05), whereas the acceleration was slower (170+/-54, 186+/-42
and 279+/-96 cm/s2, respectively, p < 0.05). Coronary flow reserve in the
patients with exercise perfusion defects (2.7+/-0.3) was significantly lower than
in those without (3.7+/-0.5, p < 0.05) or in the control group (3.4+/-0.5, p <
0.05). CONCLUSIONS: Patients with LBBB have an impairment of early diastolic
blood flow in the LAD due to an increase in early diastolic compressive
resistance resulting from delayed ventricular relaxation. Furthermore, exercise
scintigraphic perfusion defects in these patients are associated with a reduced
coronary flow reserve, indicating abnormalities of microvascular function in the
same vascular territory.
PMID- 10193737
TI - A prospective study of fibrinogen and risk of myocardial infarction in the
Physicians' Health Study.
AB - OBJECTIVES: We examined the association of baseline plasma fibrinogen with future
risk of myocardial infarction (MI) in the Physicians' Health Study. BACKGROUND:
Elevated plasma fibrinogen increases and low dose aspirin decreases risk of MI.
However, prospective data are limited about their interrelationships. METHODS:
Blood samples were prospectively collected at baseline from 14,916 men in the
Physicians' Health Study, aged 40 to 84 years, who were randomly assigned to take
aspirin (325 mg every other day) or placebo for 5 years. We measured baseline
plasma fibrinogen among 199 incident cases of MI and 199 age- and smoking-matched
control subjects free of cardiovascular disease at the time of the case's
diagnosis. RESULTS: Cases had significantly higher baseline fibrinogen levels
(geometric mean: 262 mg/dl) than did control subjects (245 mg/dl, p = 0.02).
Those with high fibrinogen levels (> or =343 mg/dl, the 90th percentile
distribution of the control subjects) had a twofold increase in MI risk (age- and
smoking-adjusted relative risk = 2.09, 95% confidence interval = 1.15 to 3.78)
compared with those with fibrinogen below 343 mg/dl. Adjustment for lipids and
other coronary risk factors as well as randomized aspirin assignment did not
materially change the result. Furthermore, we observed no interaction between
fibrinogen level and aspirin treatment. CONCLUSIONS: Among these apparently
healthy U.S. male physicians, fibrinogen is associated with increased risk of
future MI independent of other coronary risk factors, atherogenic factors such as
lipids and antithrombotics such as aspirin.
PMID- 10193738
TI - Geometric features of coronary artery lesions favoring acute occlusion and
myocardial infarction: a quantitative angiographic study.
AB - OBJECTIVES: We sought to identify the angiographic predictors of a future
infarction, to study their interaction with time to infarction, patient risk
factors and medications, and to evaluate their clinical utility for risk
stratification. BACKGROUND: Identification of coronary lesions at risk of acute
occlusion remains challenging. Stenosis severity is poorly predictive but other
stenosis descriptors might be better predictors. METHODS: Eighty-four patients
with an acute myocardial infarction and a coronary angiogram performed within the
preceding 36 months (baseline angiogram), and after infarction were selected. All
coronary stenoses (from 10% to 95% lumen diameter reduction) at baseline
angiogram were analyzed by computer-assisted quantification. Each of the 84
lesions responsible for the infarction (culprit) was compared with the nonculprit
stenoses (controls) in the same patient. RESULTS: Culprit lesions were more
symmetrical (symmetry index +15%; p < 0.001), had steeper outflow angles (maximal
angle +4 degrees; p < 0.001), were more severe (percent stenosis +5%; p = 0.001)
and longer (+ 1.5 mm, p = 0.01) than controls. The symmetry index and the outflow
angles were the two independent predictors of infarction at three-year follow-up.
Stenosis severity predicted only infarctions occurring within 1 year after
angiography. In moderately severe stenoses (40% to 70% stenosis), stratification
using the symmetry index and outflow angles accurately predicted lesions
remaining free of occlusion and infarction at three-year follow-up. CONCLUSIONS:
Better characterization of stenosis geometry might help to understand the
pathophysiologic mechanisms triggering coronary occlusion and to stratify
patients for improved care.
PMID- 10193739
TI - The shadows leave a doubt--the angiographic recognition of vulnerable coronary
artery plaques.
PMID- 10193740
TI - The presence of infection-related antiphospholipid antibodies in infective
endocarditis determines a major risk factor for embolic events.
AB - OBJECTIVES: The impact of infection-associated antiphospholipid antibodies (APA)
on endothelial cell activation, blood coagulation and fibrinolysis was evaluated
in patients with infective endocarditis with and without major embolic events.
BACKGROUND: An embolic event is a common and severe complication of infective
endocarditis. Despite the fact that APAs are known to be associated with
infectious diseases, their pathogenic role in infective endocarditis has not been
clearly defined. METHODS: The relationship among the occurrence of major embolic
events, echocardiographic vegetation size, endothelial cell activation, thrombin
generation, fibrinolysis and APA was examined in 91 patients with definite
infective endocarditis, including 26 patients with embolic events and 65 control
subjects without embolic events. RESULTS: Overall, 14.3% of patients exhibited
elevated APA levels. Embolic events occurred more frequently in patients with
elevated levels of APA than in patients without (61.5% vs. 23.1%; p = 0.008).
Patients with elevated levels of APA showed higher levels of prothrombin-fragment
F1 +2 (p = 0.005), plasminogen-activator inhibitor 1 (p = 0.0002), von Willebrand
factor (p = 0.002) and lower levels of activated protein C (p = 0.001) than
patients with normal levels of APA. Thrombin generation and endothelial cell
activation were both positively correlated with levels of APA. The occurrence of
elevated APA levels was frequently associated with structural valve abnormalities
(p = 0.01) and vegetations >1.3 cm (p = 0.002). CONCLUSIONS: Infection-associated
elevated APA levels in patients with infective endocarditis are related to
endothelial cell activation, thrombin generation and impairment of fibrinolysis.
This may contribute to the increased risk for major embolic events in these
patients.
PMID- 10193741
TI - Maternally transmitted susceptibility to non-insulin-dependent diabetes mellitus
and left ventricular hypertrophy.
AB - OBJECTIVES: We studied the association of diabetes transmission with left
ventricular hypertrophy (LVH) in patients with non-insulin-dependent diabetes
mellitus (NIDDM). BACKGROUND: It is suggested that NIDDM has a strong genetic
basis and that maternally transmitted NIDDM is associated with mitochondrial
deoxyribonucleic acid (DNA) mutations. However, genetic factors for LVH in NIDDM
are unknown. METHODS: We investigated the family history of diabetes and the
prevalence of LVH using electrocardiography in 834 patients with NIDDM, of whom
199 also underwent echocardiography. RESULTS: Of the 834 patients, 121 had
diabetic mothers, 122 had diabetic fathers and 30 had both. The LVH criterion of
S(v1) + R(V5) or R(v6) >35 mm was met in 148 patients. The percentage of patients
having diabetic mothers was higher in those with LVH criterion (29%) than without
it (16%) (p < 0.001), but the percentage of patients having diabetic fathers was
similar in those with LVH (18%) and without it (18%). Compared with the 683
patients with nondiabetic mothers, the 151 patients with diabetic mothers were
younger and had earlier onset of diabetes. The percentage of patients having
diabetic siblings was also higher in those with diabetic mothers (31%) than in
those with nondiabetic mothers (18%) (p < 0.001). On electrocardiograms, the
prevalence of LVH was higher in patients with diabetic mothers (28%) than in
those with nondiabetic mothers (15%) (p < 0.001). Echocardiograms showed that
patients with diabetic mothers had greater left ventricular wall thickness and
mass than those with nondiabetic mothers. In multivariate analysis, the family
history of diabetes in mothers was an independent factor to LVH, but the family
history of diabetes in fathers was not. CONCLUSIONS: Maternal transmission of
diabetes was associated with LVH in patients with NIDDM. Some genetic factors of
diabetes, such as mitochondrial DNA abnormalities, may contribute to the
development of LVH in maternally transmitted NIDDM.
PMID- 10193742
TI - Exercise training enhances endothelial function in young men.
AB - OBJECTIVES: The present study was designed to assess whether exercise training
can enhance endothelium-dependent dilatation in healthy young men. BACKGROUND:
Exercise has been shown to reduce cardiovascular morbidity and mortality, but the
mechanisms for this benefit are unclear. Endothelial dysfunction is an early
event in atherogenesis, and animal studies have shown that exercise training can
enhance endothelial function. METHODS: We have examined the effect of a
standardized, 10-week, aerobic and anaerobic exercise training program on
arterial physiology in 25 healthy male military recruits, aged 17 to 24 (mean 20)
years, of average fitness levels. Each subject was studied before starting, and
after completing the exercise program. Baseline vascular reactivity was compared
with that of 20 matched civilian controls. At each visit, the diameter of the
right brachial artery was measured at rest, during reactive hyperemia (increased
flow causing endothelium-dependent dilation) and after sublingual
glyceryltrinitrate (GTN; an endothelium-independent dilator), using high
resolution external vascular ultrasound. RESULTS: At baseline, flow-mediated
dilatation (FMD) and GTN-mediated dilatation were similar in the exercise and
control groups (FMD 2.2+/-2.4% and 2.4+/-2.8%, respectively, p = 0.33; GTN 13.4+/
6.2 vs. 16.7+/-5.9, respectively, p = 0.53). In the military recruits, FMD
improved from 2.2+/-2.4% to 3.9+/-2.5% (p = 0.01), with no change in the GTN
mediated dilation (13.4+/-6.2% vs. 13.9+/-5.8%, p = 0.31) following the exercise
program. CONCLUSION: Exercise training enhances endothelium-dependent dilation in
young men of average fitness. This may contribute to the benefit of regular
exercise in preventing cardiovascular disease.
PMID- 10193743
TI - A myocardial perfusion reserve index in humans using first-pass contrast-enhanced
magnetic resonance imaging.
AB - OBJECTIVES: The purpose of this study was to evaluate a myocardial perfusion
reserve index (MPRI) derived from a quantitative magnetic resonance imaging (MRI)
technique in normal human volunteers and patients with coronary artery disease
and to relate MPRI to coronary artery stenosis severity measured with
quantitative arteriography. BACKGROUND: Magnetic resonance imaging could be a
useful noninvasive tool in the investigation of ischemic heart disease. However,
there have been few studies in humans to quantify myocardial perfusion and
myocardial perfusion reserve using MRI and none in patients with coronary
disease. METHODS: Twenty patients with angiographically proven coronary artery
disease and five normal volunteers underwent both resting and stress (adenosine
140 microg/kg(-1)/min(-1)) first-pass contrast-enhanced MRI examinations (using
0.05 mmol/kg 1 of gadopentetate dimeglumine. Using a tracer kinetic model, the
unidirectional transfer constant (K(i)), a perfusion marker for the myocardial
uptake of contrast, was computed in each coronary arterial territory. The ratio
of K(i) for the rest and stress scans was used to calculate the MPRI. Percent
reduction in luminal diameter of coronary lesions was measured using an automated
edge-detection algorithm. RESULTS: Myocardial perfusion reserve index was
significantly reduced in patients compared with normal subjects (2.02+/-0.7 vs.
4.21+/-1.16, p < 0.02). For regions supplied by individual vessels, there was a
significant negative correlation of MPRI with percent diameter stenosis (r =
0.81, p < 0.01). Importantly, regions supplied by vessels with <40% diameter
stenosis (non-flow limiting) had a significantly higher MPRI than regions
supplied by stenoses of "intermediate" severity, that is, >40% to 59% diameter
stenosis (2.80+/-0.77 and 1.93+/-0.38, respectively, p < 0.02). However, even
regions supplied by vessels with <40% diameter stenosis had a significantly lower
MPRI than volunteers (p < 0.01). CONCLUSIONS: A myocardial perfusion reserve
index derived from first-pass MRI studies can distinguish between normal subjects
and patients with coronary artery disease. Furthermore, it provides useful
functional information on coronary lesions, particularly where the physiologic
significance cannot be predicted accurately from the angiogram.
PMID- 10193744
TI - Transcatheter closure of muscular ventricular septal defects with the amplatzer
ventricular septal defect occluder: initial clinical applications in children.
AB - OBJECTIVES: The aim of this study was to close muscular ventricular septal
defects (MVSDs) in children, with a new device, the Amplatzer ventricular septal
defect occluder (AVSDO). BACKGROUND: The design of previously used devices for
transcatheter closure of MVSDs is not ideal for this purpose and their use has
been limited by several drawbacks. METHODS: Six patients, aged 3 to 10 years,
with MVSDs underwent transcatheter closure using the AVSDO. The device is a
modified self-centering and repositionable Amplatzer device that consists of two
low profile disks made of Nitinol wire mesh with a 7-mm connecting waist. The
prosthesis size (connecting waist diameter) was chosen according to the measured
balloon stretched VSD diameters. A 6-F or 7-F sheath was used for the delivery of
the AVSDO. Fluoroscopy and transesophageal echocardiography were utilized for
optimal guidance. RESULTS: The location of the defect was midmuscular in five
patients and beneath the pulmonary valve in one. The balloon stretched MVSD
diameter ranged from 6 to 11 mm. Device placement was successful in all patients,
and complete occlusion occurred in all six patients (95% confidence interval
54.06% to 100%). Two patients developed transient complete left bundle branch
block. No other complications were observed. CONCLUSIONS: This encouraging
initial clinical success indicates that the AVSDO is a promising device for
transcatheter closure of MVSDs in children. Further clinical trials and longer
follow-up are needed before the widespread use of this technique can be
recommended.
PMID- 10193745
TI - Pimobendan inhibits the production of proinflammatory cytokines and gene
expression of inducible nitric oxide synthase in a murine model of viral
myocarditis.
AB - OBJECTIVES: This study was designed to examine the effects of pimobendan in a
murine model of viral myocarditis in relation to proinflammatory cytokine
production and nitric oxide (NO) synthesis by inducible NO synthase (iNOS) in the
heart. BACKGROUND: Pimobendan has been recently confirmed to improve both acute
and chronic heart failure. Since the modulation of myocardial necrosis and
contractile dysfunction by various proinflammatory cytokines may be partially
mediated by the production of nitric oxide, the effects of pimobendan on the
production ofproinflammatory cytokines and NO were investigated in an animal
model of viral myocarditis involving heart failure. METHODS: DBA/2 mice were
inoculated with the encephalomyocarditis virus. To observe its effect on survival
up to 14 days, pimobendan (0.1 mg/kg or 1 mg/kg) or vehicles were given from the
day of virus inoculation (day 0) orally once daily. The effects of pimobendan on
histological changes, cytokine production, NO production and iNOS gene expression
in the heart were studied in mice treated either with pimobendan, 1 mg/kg or with
vehicles only, and sacrificed seven days after virus inoculation. RESULTS: The
survival of mice improved in a dose-dependent fashion such that a significant
difference (p < 0.02) was found between the higher-dose pimobendan group (20 of
30 [66.7%]) and the control group (11 of 30 [36.7%]). Histological scores for
cellular infiltration (1.1+/-0.1 vs. 2.0+/-0.0, p < 0.001), intracardiac tumor
necrosis factor (TNF)-alpha (18.2+/-1.8 vs. 35.8+/-4.2 pg/mg heart, p < 0.001)
and interleukin (IL)-1beta (9.3 +/-1.2 vs. 26.6+/-7.1 pg/mg heart, p < 0.01) were
significantly lower in the mice given pimobendan versus those of the control
mice. Interleukin-6 levels (7.1+/-0.8 vs. 9.2+/-1.9 pg/mg heart) were also lower
in the mice treated with pimobendan. Furthermore, intracardiac NO production was
significantly (p < 0.001) less in the pimobendan group (0.165+/-0.004 nmol/mg
heart) than in the control group (0.291+/-0.051 nmol/mg heart), and intracardiac
iNOS gene expression in the mice given pimobendan was 74% lower than it was in
the control animals (p < 0.01). CONCLUSIONS: These findings suggest that the
beneficial effects of pimobendan in viral myocarditis are partially mediated by
the inhibition of both proinflammatory cytokine production and NO synthesis by
iNOS.
PMID- 10193746
TI - The potent platelet inhibitory effects of S-nitrosated albumin coating of
artificial surfaces.
AB - OBJECTIVES: We studied the antithrombotic effect of coating glass, collagen and
metal stent surfaces with bovine serum albumin (BSA) covalently modified to carry
S-NO functional groups denoted (pS-NO-BSA). METHODS: Video-enhanced light
microscopy was used to visualize canine blood platelet adhesion and aggregation
in a parallel plate glass chamber. Platelet adhesion was observed for 60 min on
glass, glass coated with BSA, glass coated with pS-NO-BSA, collagen I (CO)
surface, CO coated with BSA and CO coated with pS-NO-BSA. We also coated Palmaz
Shatz (P-S) stents with pS-NO-BSA. Coated and uncoated stents were then immersed
in porcine platelet-rich plasma for two min and the platelet cyclic GMP level was
measured. In six anesthetized pigs, coated and uncoated stents were placed in the
carotid arteries and [111In]-labeled platelets were circulated for 2 h. The
stented arteries were then removed and placed in a gamma well counter. RESULTS:
There was significantly less platelet attachment, adhesion and aggregation on the
pS-NO-BSA coated surfaces compared with the BSA coated and uncoated surfaces. The
pS-NO-BSA coating increased the platelet cGMP levels to 5.9+/-0.7 pmoles/10(8)
platelets compared with 2.7+/-0.9 pmoles/10(8) platelets for control (p < 0.01).
The average gamma ray count from [111In]-labeled platelets that attached to the
coated stents was 90,000+/-42,000/min and 435,000+/-290,000/min for the uncoated
stents (p < 0.01). CONCLUSIONS: The pS-NO-BSA coating of thrombogenic surfaces
reduces platelet adhesion and aggregation, possibly by increasing the platelet
cGMP. This inhibitory effect appears to be a consequence of the direct
antiplatelet actions of NO combined with the antiadhesive properties of albumin.
PMID- 10193747
TI - Mechanism of arrhythmogenicity of the short-long cardiac sequence that precedes
ventricular tachyarrhythmias in the long QT syndrome.
AB - OBJECTIVES: The purpose of this study was to investigate the electrophysiologic
mechanism(s) that underlie the transition of one or more short-long (S-L) cardiac
sequences to ventricular tachyarrhythmias (VTs) in the long QT syndrome.
BACKGROUND: One or more S-L cardiac cycles, usually the result of a ventricular
bigeminal rhythm, frequently precedes the onset of VT in patients with either
normal or prolonged QT interval. Electrophysiologic mechanisms that underlie this
relationship have not been fully explained. METHODS: We investigated
electrophysiologic changes associated with the transition of a S-L cardiac
sequence to VT in the canine anthopleurin-A model, a surrogate of LQT3.
Experiments were performed on 12 mongrel puppies after administration of
anthopleurin-A. Correlation of tridimensional activation and repolarization
patterns was obtained from up to 384 electrograms. Activation-recovery intervals
were measured from unipolar electrograms and were considered to represent local
repolarization. RESULTS: We analyzed 24 different episodes of a S-L sequence that
preceded VT obtained from 12 experiments. The VT followed one S-L sequence (five
episodes), two to five S-L sequences (12 episodes) and more than five S-L
sequences (seven episodes). The single premature ventricular beats coupled to the
basic beats were consistently due to a subendocardial focal activity (SFA). There
were two basic mechanisms for the development of VT after one or more S-L
sequences: 1) in 10 examples of a S-L sequence due to a stable unifocal bigeminal
rhythm, the occurrence of a second SFA, which arose consistently from a different
site, infringed on the pattern of dispersion of repolarization (DR) of the first
SFA to initiate reentrant excitation; 2) in the remaining 14 episodes of a S-L
sequence, a slight lengthening (50 to 150 ms) in one or more preceding cycle
lengths (CLs) resulted in alterations of the spatial pattern of DR at key sites
to promote reentry. The lengthening of the preceding CL produced differentially a
greater degree of prolongation of repolarization at midmyocardial and endocardial
sites compared with epicardial sites with consequent increase of DR. The
increased DR at key adjacent sites resulted in the development of de novo zones
of functional conduction block and/or slowed conduction to create the necessary
prerequisites for successful reentry. CONCLUSIONS: The occurrence of VT after one
or more S-L cardiac sequences was due to well defined electrophysiologic changes
with predictable consequences that promoted reentrant excitation.
PMID- 10193748
TI - Does heart failure confer a hypercoagulable state? Virchow's triad revisited.
AB - It is well-recognized that patients with congestive heart failure are at an
increased risk of stroke and venous thromboembolism. Nevertheless, stroke,
thromboembolism and myocardial infarction have generally been regarded to be end
points of secondary importance in large heart failure trials, when compared with
mortality or hospital readmissions. It may well have been that the incidence of
thrombotic events are underestimated. The problem of thrombus formation
(thrombogenesis) in heart failure may therefore be a much more significant
problem than is currently recognized. The pathophysiology of thrombogenesis in
heart failure could well be explained in the context of Virchow's original triad.
In addition to "abnormal flow" through low cardiac output, dilated cardiac
chambers and poor contractility, patients with heart failure also demonstrate
abnormalities of hemostasis and platelets (that is "abnormal blood constituents")
and endothelial dysfunction ("vessel wall abnormalities"). These abnormalities
contribute to a prothrombotic or hypercoagulable state, which increases the risk
of thrombosis in heart failure and impaired left ventricular systolic function.
Some observational data are available on the role of anticoagulants in heart
failure, and there is sound evidence to support the use of antithrombotic therapy
in patients with heart failure and atrial fibrillation. However, there are no
large-scale prospective randomized controlled trials of antithrombotic therapy in
patients with heart failure who remain in sinus rhythm, although important
studies are in progress. Although the results of these studies are awaited,
measurement of suitable markers of thrombogenesis might prove to be valuable in
identifying "high risk" patients and in determining the nature, duration and
intensity of such treatment. Further information is also needed on the predictive
value of various markers of hypercoagulability in patients with heart failure,
the association between hemostatic variables and the severity of heart failure,
and the effects of different treatments.
PMID- 10193749
TI - International cooperation in world cardiology: the role of the World Heart
Federation.
PMID- 10193750
TI - Integrity--an outmoded concept?
PMID- 10193751
TI - President's page: convocation address.
PMID- 10193752
TI - Reduction of tumour blood flow with KB-R8498 potentiates the response of tumours
to hyperthermia.
AB - The anti-tumour activity and the effect on tumour and normal tissue perfusion of
a newly discovered anticancer agent, KB-R8498 (Kanebo Ltd., Osaka, Japan), were
investigated in FSa II tumours of C3H mice. The tumour perfusion, as measured by
the 86Rb-uptake method, markedly decreased with relatively little change in the
normal tissue perfusion after an i.v. injection of KB-R8498. Furthermore, the
drug potentiated the effect of hyperthermia at 42.5 degrees C for 60 min to
suppress the tumour growth. The results suggest that the preferential reduction
in tumour blood flow relative to normal tissue blood flow by KB-R8498 may be
exploited to enhance the anti-tumour effect of hyperthermia.
PMID- 10193753
TI - Modification of tirapazamine-induced cytotoxicity in combination with mild
hyperthermia and/or nicotinamide: reference to effect on quiescent tumour cells.
AB - C3H/He and Balb/c mice bearing SCC VII or EMT6/KU tumours received continuous
administration of 5-bromo-2'-deoxyuridine (BrdU) for 5 days to label all
proliferating (P) cells. The tumours were locally heated at 40 degrees C for 60
min and/or the tumour-bearing mice received intraperitoneal injection of
nicotinamide, and then tirapazamine (TPZ) was injected intraperitoneally. Sixty
minutes after TPZ injection, the tumours were excised, minced and trypsinized.
The tumour cell suspensions were incubated with cytochalasin-B (a cytokinesis
blocker), and the micronucleus (MN) frequency in cells without BrdU labelling
(quiescent (Q) cells) was determined using immunofluorescence staining for BrdU.
The MN frequency in total (P+Q) tumour cells was determined from the tumours that
were not pretreated with BrdU. The cytotoxicity of TPZ was evaluated in terms of
the frequency of induced micronuclei in binuclear tumour cells (= MN frequency).
In both tumour systems, the MN frequencies of Q cells were greater than those of
total tumour cell populations. Mild heat treatment elevated the MN frequency in
total and Q cells in both tumour systems, but the effect was more marked in Q
cells. In total cells, mild heat treatment increased the MN frequency in EMT6/KU
tumour cells more markedly than in SCC VII tumour cells. In contrast, in both
tumour systems, nicotinamide decreased the MN frequency in both cell populations,
with a greater influence on the total cells. The combination of TPZ and mild heat
treatment may be useful for sensitizing tumour cells in vivo, including Q cells.
PMID- 10193754
TI - Thermal radiosensitization and repair inhibition in human melanoma cells: a
comparison of survival and DNA double strand breaks.
AB - Human melanoma cells (SK-mel-3) were treated with combinations of radiation and
hyperthermia treatment and survival (using the colony forming assay) and DNA
double strand breaks (dsb's) (using pulsed field gel electrophoresis) were
measured for immediate and delayed plating. The cells were treated in plateau
phase, so that delayed plating would result in repair of potentially lethal
damage (PLD). Delayed plating showed PLDR for both the survival and the dsb end
point. One hour of heating after irradiation showed a temperature dependent
increase in radiosensitization for both the survival endpoint and the dsb
endpoint for the temperature range from 42 to 45 degrees C. One hour of heating
at 43 degrees C after irradiation resulted in the partial inhibition of PLDR and
recovery of dsb's. For heating at 45 degrees C the inhibition of dsb repair was
complete. There was good correlation between the survival endpoint and the dsb
endpoint for the thermal radiosensitization for both the immediate plating and
the PLDR protocols. These data indicate that hyperthermia inhibition of repair of
PLD is probably due to the inhibition of dsb rejoining. These correlations were
made at the same dose levels for survival and dsb analysis, thus avoiding the
potential complications of many earlier studies which used much higher doses for
dsb analysis than for survival studies.
PMID- 10193755
TI - Spectrofluorometric and microcalorimetric study of the thermal poration relevant
to the mechanism of thermohaemolysis.
AB - This study sheds light on the structural changes in erythrocyte membrane during
thermally induced poration, an event involved in thermohaemolysis. Two major
membrane disturbing events can be induced during transient heating, the
denaturation of spectrin and thermoporation. The first one precedes the latter
but is not involved in it. Ethanol linearly reduces the onset temperature of both
events but with different efficiencies. Thermoporation efficiency exceeds by 3.5
fold that of spectrin denaturation. Thus, at a specific concentration of ethanol
(18% v/v), the poration occurs at 39.5 degrees C, which precedes the denaturation
of spectrin by 6 degrees C. To induce and study the poration avoiding spectrin
denaturation, cells were put in contact with preheated (39 degrees C) isotonic
(60mM) NaCl) media containing 18% v/v ethanol and sucrose as an osmotic
protectant. After 3 min heating, the porated cells were washed, their membranes
isolated and studied. The control cells were processed similarly except that they
were incubated at 23 degrees C, thus avoiding thermoporation. Using scanning
microcalorimetry, the enthalpy and the temperature of denaturation of spectrin
were found to be the same in control as well as in porated membranes which
indicates similar spectrin structure in both membranes. While the enthalpy of
denaturation of the anion channel was preserved, its denaturation temperature was
lowered by 2.5 degrees C after poration. These results confirmed that the heat
denaturation of the main membrane proteins was not needed and not involved in
thermoporation and, hence, in thermohaemolysis. Analysis of the fluorescence of
membrane bound ANS gave an apparent increase in the number of binding sites for
ANS in membranes after poration. In relation to the control, the eximerization of
pyrene in porated membranes changed, depending on the location of the probe: in
the domain of free lipids it decreased by 18% but it increased by 60% in the
lipid milieu proximal to membrane proteins. Likewise, the eximerization of N-(3
Pyrene) maleimide bound to membrane proteins increased by 67% after poration,
which proves increased intramolecular mobility of proteins following poration.
The maximal efficiency for transferring energy from tryptophans to neighbouring
pyrene was determined to be 0.93 in control, which is almost the same as in
intact membranes, and 0.70 in porated membranes, indicating a strong decrease in
the lipid/protein contact zone. This data suggests a mild conformational change,
possibly an irreversible perturbance of the transbilayer distribution of membrane
proteins in porated membranes in comparison to the control and intact ones.
PMID- 10193756
TI - An adaptive microwave phased array for targeted heating of deep tumours in intact
breast: animal study results.
AB - It has previously been reported in phantoms, that an adaptive radiofrequency
phased array can generate deep focused heating distributions without overheating
the skin and superficial healthy tissues. The present study involves adaptive
microwave phased array hyperthermia tests in animals (rabbits) with and without
tumours. The design of the adaptive phased array as applied to the treatment of
tumours in intact breast, is described. The adaptive phased array concept uses
breast compression and dual-opposing 915 MHz air-cooled waveguide applicators
with electronic phase shifters and electric-field feedback, to focus
automatically by computer control the microwave radiation in deep tissue.
Temperature measurements for a clinical adaptive phased array hyperthermia system
demonstrate tissue heating at depth with reduced skin heating.
PMID- 10193757
TI - Thermotherapy: feasibility study using a single focussed ultrasound transducer.
AB - Feasibility studies on tissue lesioning using high intensity focussed ultrasound
(HIFU) thermotherapy were carried out. A single strongly focussed transducer was
used. The transducer has a diameter of 50 mm, a centre resonance frequency of 1
MHz and a focal distance of 50mm. Experiments were carried out both in vitro on
pig muscle samples and in vivo on a pig (exposures on the thigh and on the
liver). Different types of burst pulse signals were used, the best results were
obtained with 1-2 s burst pulses, with a repetition period of 10s. The risk for
skin damage increases for longer burst pulses. Lesions at the focus were obtained
both in the experiments in vitro as well as in vivo. The size and the shape of
the lesions in vivo resemble those obtained in vitro. The results of the
experiments show that tissue lesions can be obtained at deep locations (4.5 cm in
the tissue) with the transducer. The lesions were well discriminated from the
surrounding tissue and were ellipsoid- or drop-shaped. The lesion size can be
controlled by the choice of time parameters of the burst pulse signal, power and
treatment time. Temperatures of about 80 degrees C were measured in the tissue at
the ultrasound focus in vitro. These results show that elevated temperatures can
be induced rapidly at the focus, thus reducing the effect of heat dissipation
through blood perfusion.
PMID- 10193758
TI - A mathematical model of cell growth and alkane degradation in Wadden Sea sediment
suspensions.
AB - In a series of 16 experiments, hexadecane in different concentrations was mixed
with natural Wadden Sea sediments, and the degradation of the alkane was observed
under controlled conditions (bioreactor). The aim of the experiments was to
quantify the impact of the dissolved oxygen tension and the initial alkane
concentration on degradation time and degradation completeness. A mathematical
model was constructed which is able to reproduce reasonably well the observed
time series under all conditions: aerobic and nearly anaerobic, diluted and
alkane-saturated. The model contains hypotheses on the chain of reactions; it
attempts to bridge existing gaps in the understanding of the degradation process.
PMID- 10193759
TI - Modelling effects of high product and substrate inhibition on oscillatory
behavior in continuous bioreactors.
AB - In this study we consider a model for continuous bioreactors which incorporates
the effects of high product and substrate inhibition on the kinetics as well as
biomass and product yields. We theoretically investigate the possibility of
various dynamic behaviors in the bioreactor over different ranges of operating
parameters to determine the delineating process conditions which may lead to
oscillatory behavior. Application of the singular perturbation technique allows
us to derive explicit conditions on the system parameters which specifically
ascertain the existence of limit cycles composed of concatenations of
catastrophic transitions occurring at different speeds. We discover further that
the interactions between the limiting substrate and the growing microorganisms
can give rise to high frequency oscillations which can arise during the
transients toward the attractor or during the low-frequency cycle. Such a study
not only can describe more fully the kinetics in a fermentor but also assist in
formulating optimum fermentor operating conditions and in developing control
strategy for maintaining optimum productivity.
PMID- 10193760
TI - Rule-based programming paradigm: a formal basis for biological, chemical and
physical computation.
AB - A rule-based programming paradigm is described as a formal basis for biological,
chemical and physical computations. In this paradigm, the computations are
interpreted as the outcome arising out of interaction of elements in an object
space. The interactions can create new elements (or same elements with modified
attributes) or annihilate old elements according to specific rules. Since the
interaction rules are inherently parallel, any number of actions can be performed
cooperatively or competitively among the subsets of elements, so that the
elements evolve toward an equilibrium or unstable or chaotic state. Such an
evolution may retain certain invariant properties of the attributes of the
elements. The object space resembles Gibbsian ensemble that corresponds to a
distribution of points in the space of positions and momenta (called phase
space). It permits the introduction of probabilities in rule applications. As
each element of the ensemble changes over time, its phase point is carried into a
new phase point. The evolution of this probability cloud in phase space
corresponds to a distributed probabilistic computation. Thus, this paradigm can
handle tor deterministic exact computation when the initial conditions are
exactly specified and the trajectory of evolution is deterministic. Also, it can
handle probabilistic mode of computation if we want to derive macroscopic or bulk
properties of matter. We also explain how to support this rule-based paradigm
using relational-database like query processing and transactions.
PMID- 10193761
TI - Quantum mechanics in the present progressive mode and its significance in
biological information processing.
AB - Quantum mechanics practiced in the present progressive mode can incorporate into
itself the propagation of a signal of a local character. It is possible to view
that any movement in the present progressive mode is mutli-agential in the sense
of internal interactions due to the absence of an external agency coordinating
the global situation simultaneously. The idea of living memory is discussed as
carrying the leftover from those actions completed and registered in the present
perfect mode and surviving at any present moment. The occurrence of both the
signal propagation of a local character and living memory is upheld upon exchange
interaction of a quantum mechanical origin. Empirical evidence suggesting the
likelihood of such an exchange interaction is found in the neurotransmitter-gated
ion channels located on the plasma membrane of the muscle cell in the vicinity of
secretory vesicles containing acetylcholine near the nerve terminal. Another case
from the empirical evidence is seen in the actomyosin system demonstrating the
unidirectional propagation of variations in the acceleration of the displacement
of an actin filament sliding on myosin molecules in the presence of ATP
molecules.
PMID- 10193762
TI - Identification of novel polymorphisms within the promoter region of the human
beta2 adrenergic receptor gene.
AB - By screening the 1470 bp 5' to the start codon of the human beta2 adrenergic
receptor gene, we have identified a total of eight polymorphisms (-20 T-->C, -47
T-->C, -367 T-->C, -468 C-->G, -654 G-->A, -1023 G-->A, -1343 A-->G and -1429 T-
>A c.f. beta2 adrenergic receptor start codon). Transient transfection of 5'
flanking deletion luciferase reporter constructs demonstrated the majority of
activity of the human beta2 adrenergic gene 5' flanking region to be present
within a 549 bp fragment immediately upstream from the start codon. Because of
linkage disequilibrium, some combinations of polymorphisms were particularly
frequent. We transiently transfected COS-7 cells with luciferase constructs under
the control of the 549 bp of 5' flanking DNA containing the two most frequent
extended haplotypes in this region. Luciferase activity was significantly reduced
in cells transfected with the 'mutant' construct (-20C, -47C, -367C, -468G) c.f.
the 'wild-type' construct (-20T, -47T, -367T, -468C). These data suggest that
polymorphisms have the potential to alter human beta2 adrenergic receptor gene
expression.
PMID- 10193763
TI - Effects of the adenylyl cyclase inhibitor SQ22536 on iloprost-induced
vasorelaxation and cyclic AMP elevation in isolated guinea-pig aorta.
AB - The stable prostacyclin analogue, iloprost relaxes a variety of blood vessels and
increases cyclic AMP, although the relationship between adenosine 3': 5'-cyclic
monophosphate (cyclic AMP) and vasorelaxation remains unclear. We therefore
investigated the effect of the adenylyl cyclase inhibitor, 9-(tetrahydro-2
furanyl)-9H-purin-6-amine (SQ22536) on iloprost-mediated relaxation and cyclic
AMP elevation in endothelium-denuded aortic strips. Iloprost (1-1000 nM) caused a
concentration-dependent inhibition of phenylephrine (1-6 microM) contractions,
the responses being unaffected by pre-incubation with SQ22536 (100 microM) for 30
min. In other experiments 60 nM iloprost caused a 64% inhibition of phenylephrine
contractions concomitant with a 3 fold rise in cyclic AMP. SQ22536 completely
abolished the iloprost-induced elevation in cyclic AMP while having no
significant effect on relaxation. Our results therefore strongly suggest that
cyclic AMP-independent pathways are responsible for the vasorelaxant effects of
iloprost in guinea-pig aorta.
PMID- 10193764
TI - Effects of the prostanoid EP3-receptor agonists M&B 28767 and GR 63799X on
infarct size caused by regional myocardial ischaemia in the anaesthetized rat.
AB - 1. This study investigates the effects of two agonists of the prostanoid EP3
receptor (M&B 28767 and GR 63799X) on the infarct size caused by regional
myocardial ischaemia and reperfusion in the anaesthetized rat. 2. One hundred and
sixty-seven, male Wistar rats were anaesthetized (thiopentone, 120 mg kg(-1)
i.p.), ventilated (8-10 ml kg(-1), 70 strokes min(-1), inspiratory oxygen
concentration: 30%; PEEP: 1-2 mmHg) and subjected to occlusion of the left
anterior descending coronary artery (LAD, for 7.5, 15, 25, 35, 45 or 60 min)
followed by reperfusion (2 h). Infarct size was determined by staining of viable
myocardium with a tetrazolium stain (NBT), histological evaluation by light and
electron microscopy and determination of the plasma levels of cardiac troponin T.
3. M&B 28767 (0.5 microg kg(-1) min(-1), i.v., n=7) or GR 63799X (3 microg kg(-1)
min(-1), i.v., n=7) caused significant reductions in infarct size from 60+/-3%
(25 min ischaemia and 2 h reperfusion; saline-control, n=8) to 39+/-6 and 38+/-4%
of the area at risk, without causing a significant fall in blood pressure.
Pretreatment of rats with 5-hydroxydecanoate (5-HD), an inhibitor of ATP
sensitive potassium channels, attenuated the cardioprotective effects of both EP3
receptor agonists. The reduction in infarct size afforded by M&B 28767 was also
abolished by glibenclamide and the protein kinase C (PKC) inhibitors
staurosporine and chelerythrine. 4. Thus, M&B 28767 and GR 63799X reduce
myocardial infarct size in the rat by a mechanism(s) which involves the
activation of PKC and the opening of ATP-sensitive potassium channels.
PMID- 10193765
TI - Prostanoid receptors involved in the relaxation of human pulmonary vessels.
AB - 1. To characterize the prostanoid receptors on human pulmonary smooth muscle
involved in vasodilatations, isolated arteries and veins were contracted with
norepinephrine (10 microM) and vessels were subsequently challenged with
different prostanoid-receptor agonists in the absence or presence of selective
antagonists. 2. Prostaglandin D2 (PGD2) and the selective DP-receptor agonist,
BW245C, induced relaxations in the contracted human pulmonary venous
preparations. The pD2 values were: 6.88+/-0.11 (n=17) and 7.31+/-0.12 (n=5),
respectively. The relaxant responses induced by PGD2 were reduced by the
selective DP-receptor antagonist, BWA868C, and the estimated pA2 value was 7.84+/
0.16 (n=4). PGD2 and BW245C did not relax contracted human pulmonary arteries. 3.
The selective IP-receptor agonists, iloprost and cicaprost, both induced
relaxations in the contracted human vascular preparations. The pD2 values for
iloprost were: 7.84+/-0.08 (n=6) and 8.25+/-0.06 (n=4) and for cicaprost: 8.06+/
0.12 (n=5) and 8.11+/-0.09 (n=5) in arteries and veins respectively. 4.
Prostaglandin E2 (PGE2) and the EP2/EP3-receptor agonist, misoprostol, partially
relaxed the contracted venous preparations and the pD2 values were: 8.10+/-0.15
(n=15) and 6.24+/-0.33 (n=3), respectively. These relaxations suggest the
presence of an EP receptor in the human pulmonary veins. The contracted human
pulmonary arteries did not relax when challenged with PGE2. 5. In human pulmonary
venous preparations, the PGE2-induced relaxations were neither modified by
treatment with TP/EP4-receptor antagonist, AH23848B (10 and 30 microM, n=6), nor
by the DP/EP1/EP2-receptor antagonist, AH6809 (3 microM, n=6). 6. These data
suggest that the relaxation induced by prostanoids involved DP-, IP-receptors and
to a lesser extent an EP-receptor on human pulmonary venous smooth muscle. In
contrast, only the IP-receptor is involved in the prostanoid induced relaxations
on human pulmonary arterial smooth muscle.
PMID- 10193766
TI - Prostanoid receptors involved in the relaxation of human bronchial preparations.
AB - 1. Iloprost and cicaprost (IP-receptor agonists) induced relaxations in the
histamine- (50 microM) contracted human bronchial preparations (pD2 values,
6.63+/-0.12 and 6.86+/-0.08; Emax values, 90+/-04 and 65+/-08% of the papaverine
response for iloprost (n=6) and cicaprost (n=3), respectively). 2. Prostaglandin
E2 (PGE2) and misoprostol (EP-receptor agonist) relaxed the histamine-contracted
human bronchial preparations (pD2 values, 7.13+/-0.07 and 6.33+/-0.28; Emax
values, 67+/-04 and 57+/-08% of the papaverine response for PGE2 (n=14) and
misoprostol (n=4), respectively). In addition, both relaxations were inhibited by
AH6809 (DP/EP1/EP2-receptor antagonist; 3 microM; n=5-6). 3. The PGE2-induced
relaxations of human bronchial preparations were not modified by treatment with
AH23848B (TP/EP4-receptor antagonist; 30 microM; n=4). 4. The contracted human
bronchial preparations were significantly relaxed by prostaglandin D2 (PGD2) or
by BW245C a DP-receptor agonist. However, these responses did not exceed 40% of
the relaxation induced by papaverine. In addition, the relaxations induced by
PGD2 were significantly inhibited by treatment with a DP-receptor antagonist
BWA868C (0.1 microM; n=3). 5. These data suggest that the relaxation of human
isolated bronchial preparations induced by prostanoids involved IP-, EP2- and to
a lesser extent DP-receptors but not EP4-receptor.
PMID- 10193767
TI - Effects of varying the expression level of recombinant human mGlu1alpha receptors
on the pharmacological properties of agonists and antagonists.
AB - 1. Different expression levels of the human type 1alpha metabotropic glutamate
(mGlu1alpha) receptor were obtained in transfected Chinese hamster ovary cells
using an isopropyl beta-D-thiogalactopyranoside (IPTG) inducible system.
Expression of mGlu1alpha receptors could not be detected using immunoblotting or
immunocytochemical approaches in non-induced cells, however, controlled
expression could be induced following IPTG addition in a time- and concentration
dependent manner. 2. In induced cells (100 microM IPTG, 20 h) the agonists L
quisqualate or 1-aminocyclopentane-1S,3R-dicarboxylic acid stimulated large
increases in [3H]-inositol (poly)phosphate (in the presence of Li+) and inositol,
1,4,5-trisphosphate levels. 3. Induction with 1-100 microM IPTG allowed the
receptor density to be increased incrementally and this not only resulted in an
increase in the maximum response to L-quisqualate, 1-aminocyclopentane-1S,3R
dicarboxylic acid and (S)-3,5-dihydroxy-phenylglycine, but also in an increase in
the respective potencies of each agent to activate phosphoinositide hydrolysis.
4. The intrinsic activity of the partial agonist 1-aminocyclopentane-1S,3R
dicarboxylic acid dramatically increased with increasing receptor expression. 5.
The activities of the competitive mGlu1alpha receptor antagonists (S)-alpha
methyl-4-carboxyphenylglycine and (S)-4-carboxy-3-hydroxyphenylglycine for
inhibition of the effects of L-quisqualate or (S)-3,5-dihydroxyphenylglycine were
found to be independent of the receptor expression level. 6. When the mGlu1alpha
receptor was expressed at very high levels, no evidence for receptor constitutive
activity could be detected, and none of the antagonists tested revealed either
any intrinsic activity or negative efficacy. 7. These data demonstrate that both
the potency and efficacy of mGlu1alpha receptor agonists are influenced by
expression level, whilst mGlu1alpha receptor antagonist activities are
independent of expression level.
PMID- 10193768
TI - Neural modulation of the cyclic electrical and mechanical activity in the rat
colonic circular muscle: putative role of ATP and NO.
AB - 1. The rat colonic circular muscle displays cyclic episodes of myenteric
potential oscillations (MPOs), each of them associated with a spontaneous
contraction. Nifedipine 1 microM abolished both MPOs and their associated
contractions. TTX (1 microM) increased the amplitude and frequency of spontaneous
contractions. 2. Electrical field stimulation (EFS) induced a non-adrenergic non
cholinergic (NANC) inhibitory junction potential (IJP), with two phases: an
initial fast hyperpolarization (characterized by IJP amplitude) and a sustained
hyperpolarization (characterized by IJP duration). 3. Sodium nitroprusside (10
microM) hyperpolarized and abolished spontaneous contractions even in presence of
TTX or 1 microM apamin. ATP (100 microM) also hyperpolarized and abolished
spontaneous contractions but its effects were decreased by TTX and abolished by
apamin. 4. Suramin (100 microM) or apamin reduced the amplitude of the IJPs, but
did not affect their duration. Incubation with L-NOARG (1 mM) reduced the
duration but not the amplitude of the IJPs. In presence of L-NOARG plus suramin
or L-NOARG plus apamin, both duration and amplitude of the IJPs were reduced but
a residual IJP could still be recorded. 5. We conclude that the mechanical and
electrical cyclic activity of the rat colonic circular muscle is modulated but
not originated by the enteric nervous system and involves L-type calcium channel
activity. EFS induces release of NANC inhibitory neurotransmitters which
hyperpolarize and relax smooth muscle cells. Both ATP and NO are involved in IJP
generation: ATP is responsible for the first phase of the IJPs involving
activation of apamin-sensitive potassium channels, whereas NO initiates the
second phase which is independent of the activation of such channels.
PMID- 10193769
TI - Selective activation of excitation-contraction coupling pathways by ET(A) and
ET(B) receptors in guinea-pig tracheal smooth muscle.
AB - 1. Signalling events responsible for endothelin(A) (ET(A)) and ET(B) receptor
induced contraction were examined in epithelium-denuded guinea-pig tracheal
smooth muscle strips. Selective stimulation of each subtype was achieved by a
combination of ET-1 (100 nM) and ET(A) and ET(B) receptor-selective antagonists,
BQ-123 (10 microM) and BQ-788 (3 microM), respectively. 2. Both ET(A) and ET(B)
receptors induced long-lasting contraction that was totally dependent on Ca2+
influx. Stimulation of ET(A) receptor induced both transient and sustained
(Ca2+)i increases whereas that of ET(B) receptor induced only a sustained
increase. Suppression of the transient (Ca2+)i increase by U73122 (3 microM) did
not affect the ET(A)-induced sustained (Ca2+)i increase and tension development.
Stimulation of ET(A) receptor, but not ET(B), induced phosphoinositide breakdown
and protein kinase C (PKC). The activated PKC contributed to the contraction by
increasing the Ca2+ sensitivity of the contractile apparatus. 3. Thus, ET(A)
receptor is coupled both with phospholipase C/Ca2+/PKC signalling and Ca2+ influx
pathways whereas ET(B) receptor was coupled only with the latter. 4. Stimulation
of ET(B) receptor, but not ET(A), caused membrane depolarization measured with a
fluorescent indicator, bis-(1,3 dibutylbarbituric acid)-trimethine oxonol. Both
nifedipine (1 microM) and verapamil (10 microM) abolished ET(B)-induced Ca2+
influx and contraction, while they barely affected ET(A)-induced responses. 5.
Therefore, the Ca2+ influx pathways activated by each subtype appeared to be
completely different; ET(A) and ET(B) receptors opens voltage-independent Ca2+
channels and L-type voltage-dependent Ca2+ channels, respectively.
PMID- 10193770
TI - Inhibition of inflammatory actions of aminobisphosphonates by dichloromethylene
bisphosphonate, a non-aminobisphosphonate.
AB - 1. When injected intraperitoneally into mice in doses larger than those used
clinically, all the amino derivatives of bisphosphonates (aminoBPs) tested induce
a variety of inflammatory reactions such as induction of histidine decarboxylase
(HDC, the histamine-forming enzyme), hypertrophy of the spleen, atrophy of the
thymus, hypoglycaemia, ascites and accumulation of exudate in the thorax, and an
increase in the number of macrophages and/or granulocytes in the peritoneal
cavity of blood. On the other hand, dichloromethylene bisphosphonate (Cl2MBP) a
typical non-aminoBP, has no such inflammatory actions. In the present study, we
found that this agent can suppress the inflammatory actions of aminoBPs. 2.
Cl2MBP, when injected into mice before or after injection of 4-amino-1
hydroxybutylidene-1,1-bisphosphonic acid (AHBuBP; a typical aminoBP), inhibited
the induction of HDC activity by AHBuBP in a dose- and time-dependent manner. The
increase in HDC activity induced by AHBuBP was largely suppressed by the
injection of an equimolar dose of Cl2MBP. Cl2MBP also inhibited other AHBuBP
induced inflammatory reactions, as well as the inflammatory actions of two other
aminoBPs. However, Cl2MBP did not inhibit the increase in HDC activity induced by
lipopolysaccharide (LPS). 3. We have previously reported that AHBuBP augments the
elevation of HDC activity and the production of interleukin-1beta (IL-1beta) that
are induced by LPS. These actions of AHBuBP were also inhibited by Cl2MBP. 4.
Based on these results and reported actions of bisphosphonates, the mechanisms
underlying the contrasting effects of aminoBPs and Cl2MBP, a non-aminoBP are
discussed. The results suggest that combined administration of Cl2MBP and an
aminoBP in patients might be a useful way of suppressing the inflammatory side
effects of aminoBPs.
PMID- 10193771
TI - Studies on the role of dopamine in the degeneration of 5-HT nerve endings in the
brain of Dark Agouti rats following 3,4-methylenedioxymethamphetamine (MDMA or
'ecstasy') administration.
AB - 1. We investigated whether dopamine plays a role in the neurodegeneration of 5
hydroxytryptamine (5-HT) nerve endings occurring in Dark Agouti rat brain after
3,4-methylenedioxymethamphetamine (MDMA or 'ecstasy') administration. 2.
Haloperidol (2 mg kg(-1) i.p.) injected 5 min prior and 55 min post MDMA (15 mg
kg(-1) i.p.) abolished the acute MDMA-induced hyperthermia and attenuated the
neurotoxic loss of 5-HT 7 days later. When the rectal temperature of MDMA +
haloperidol treated rats was kept elevated, this protective effect was marginal.
3. MDMA (15 mg kg(-1)) increased the dopamine concentration in the dialysate from
a striatal microdialysis probe by 800%. L-DOPA (25 mg kg(-1) i.p., plus
benserazide, 6.25 mg kg(-1) i.p.) injected 2 h after MDMA (15 mg kg(-1)) enhanced
the increase in dopamine in the dialysate, but subsequent neurodegeneration was
unaltered. L-DOPA (25 mg kg(-1)) injected before a sub-toxic dose of MDMA (5 mg
kg(-1)) failed to induce neurodegeneration. 4. The MDMA-induced increase in free
radical formation in the hippocampus (indicated by increased 2,3- and 2,5
dihydroxybenzoic acid in a microdialysis probe perfused with salicylic acid) was
unaltered by L-DOPA. 5. The neuroprotective drug clomethiazole (50 mg kg(-1)
i.p.) did not influence the MDMA-induced increase in extracellular dopamine. 6.
These data suggest that previous observations on the protective effect of
haloperidol and potentiating effect of L-DOPA on MDMA-induced neurodegeneration
may have resulted from effects on MDMA-induced hyperthermia. 7. The increased
extracellular dopamine concentration following MDMA may result from effects of
MDMA on dopamine re-uptake, monoamine oxidase and 5-HT release rather than an
'amphetamine-like' action on dopamine release, thus explaining why the drug does
not induce degeneration of dopamine nerve endings.
PMID- 10193772
TI - Enhanced role for the opening of potassium channels in relaxant responses to
acetylcholine after myocardial ischaemia and reperfusion in dog coronary
arteries.
AB - 1. Anaesthetized dogs were subjected to 1 h occlusion of the left circumflex
coronary artery followed by 2 h of reperfusion. Relaxant responses were examined
in coronary artery rings removed proximal (nonischaemic) or distal (ischaemic) to
the site of occlusion. 2. Relaxant responses to acetylcholine (ACh) were similar
in nonischaemic and ischaemic artery rings. In addition ACh-induced relaxation of
nonischaemic and ischaemic artery rings was equally susceptible to inhibition of
nitric oxide (NO) synthase using L-N(G)-nitroarginine (L-NOARG, 10(-4) M), or to
inhibition of soluble guanylate cyclase using 1H-[1,2,4]oxadiazolo[4,3
a]quinoxaline-1-one (ODQ, 10(-5) M). 3. In nonischaemic arteries, the relaxation
to ACh was unaffected by high K+ (67 mM) but in ischaemic arteries, the maximum
relaxation to ACh was significantly reduced from 113+/-6 to 60+/-2% (ANOVA,
P<0.05). Tetraethylammonium (TEA, 10(-3) M), an inhibitor of large conductance
calcium activated potassium (BK(Ca)) channels did not inhibit the response to ACh
in nonischaemic arteries but in ischaemic arteries TEA significantly shifted the
concentration response curve to ACh to the right (pEC(50); nonischaemic, 7.07+/
0.25; ischaemic, 6.54+/-0.21, P<0.01, ANOVA) without decreasing the maximum
relaxation. TEA did not affect the responses to sodium nitroprusside in either
nonischaemic or ischaemic arteries. 4. In conclusion, ischaemia/reperfusion did
not change the sensitivity of endothelium-dependent relaxation to L-NOARG or ODQ
indicating that ischaemia did not affect the contribution of NO or cyclic GMP to
ACh-induced relaxation. However, in ischaemic arteries the opening of the BK(Ca)
channels contributed to relaxation caused by ACh whereas TEA had no effect in
nonischaemic arteries. The factor responsible for the opening of this potassium
channel was a factor other than NO and may be endothelium derived hyperpolarizing
factor (EDHF).
PMID- 10193773
TI - Decreased vascular permeability response to substance P in airways of genetically
hypertensive rats.
AB - 1. The inbred genetically hypertensive strain (GH) of the Otago Wistar rat
possesses more sensory neurons containing the neuropeptide substance P (SP) than
does its genetically related control normotensive strain. 2. As SP contributes to
airway inflammation by increasing microvascular permeability, we assessed the
extravasation of Evans Blue dye in trachea and main bronchus of anaesthetized GH
and control rats, in the presence of endogenous (capsaicin-liberated) or
exogenous SP. 3. Following intravenous administration of either capsaicin (75
microg kg(-1)) or SP (3.3 nmol kg(-1)), extravasation of Evans Blue in airways
from GH rats was only about 60% of that in airways of control rats. This
difference was not gender-specific and responses to capsaicin were abolished by
pretreatment with a selective NK1 receptor antagonist SR 140333 (360 nmol kg(
1)). 4. By contrast, the extravasation of dye caused by intravenous 5
hydroxytryptamine (0.5 micromol kg(-1)) was similar in magnitude in both GH and
control strains. 5. Falls in systemic arterial blood pressure in response to
exogenous SP (0.1-3 nmol kg(-1)) or acetylcholine (0.2-2 nmol kg(-1)) were also
very similar between strains, but those in response to capsaicin (75 microg kg(
1)) in the GH rats were about double those in control rats. The hypotensive
response to SP was abolished by SR 140333, but that to capsaicin was unaffected.
6. Our results indicate that the increased peripheral innervation density by SP
nerves in GH rats is accompanied by reduced inflammatory responses to SP. This
does not involve decreased vasodilator potency of SP and is therefore probably
related to altered endothelial responsiveness.
PMID- 10193774
TI - G-protein activation by putative antagonists at mutant Thr373Lys alpha2A
adrenergic receptors.
AB - 1. Replacement of a threonine by a lysine at position 373 in the C-terminal
portion of the third intracellular loop of the human alpha2A-adrenergic receptor
(alpha2A AR) has been reported to generate a constitutively active mutant
receptor in analogy with similar mutations in the alpha1B and beta2 AR (Ren et
al., 1993). In the present study, the mutant Thr373Lys alpha2A AR receptor was
investigated by measuring the formation of inositol phosphates in either the
absence or presence of mouse G(alpha)15 protein in Cos-7 cells. 2. Increased
affinity, potency and/or efficacy for the agonists [(-)-adrenaline, UK 14304,
clonidine, guanabenz and oxymetazoline] was observed, consistent with a
precoupled mutant alpha2A AR: G-protein state. The basal inositol phosphates
response was similar at the wild-type (wt) and mutant alpha2A AR, but was
enhanced at the mutant alpha2A AR upon co-expression with the mouse G(alpha)15
protein. This enhanced response could not be attenuated in the presence of any of
the tested alpha2 AR antagonists (10 microM), suggesting that inverse agonist
activity did not occur at the mutant alpha2A AR. 3. Ligands that so far have been
identified as antagonists at the wt alpha2A AR demonstrated either no intrinsic
activity (MK 912, WB 4101, RS 15385, RX 811059 and RX 821002) or positive
efficacy [Emax, % vs. 1 microM UK 14304: dexefaroxan (27+/-7), idazoxan (34+/-9),
atipamezole (27+/-4), BRL 44408 (59+/-5) and SKF 86466 (54+/-9)] at the mutant
alpha2A AR, but only in the presence of the mouse G(alpha)15 protein. The ligand
potencies corresponded with their respective pKi values at the mutant alpha2A AR
receptor. 4. The partial agonist effect of SKF 86466 was resistant to pertussis
toxin treatment (100 ng ml(-1)) and not affected by co-expression of the rat
G(alpha)i1 protein. It was virtually absent in the presence of 10 microM RS
15385. SKF 86466 was without intrinsic activity upon co-expression of the mouse
G(alpha)q protein. 5. Some putative alpha2 AR antagonists exerted a partial
agonist activity that was highly dependent on the presence of specific G-protein
alpha-subunits, suggesting that these ligands cause selective G-protein
activation at the mutant alpha2A AR.
PMID- 10193775
TI - Inhibition of the production of endothelium-derived hyperpolarizing factor by
cannabinoid receptor agonists.
AB - 1. The endogenous cannabinoid, anandamide, has been reported to induce an
'endothelium-derived hyperpolarizing factor (EDHF)-like' relaxation in vitro. We
therefore investigated the effects of cannabinoid CB1 receptor agonists; HU 210,
delta9-tetrahydrocannabinol (delta9-THC) and anandamide, and a CB1
antagonist/inverse agonist, SR 141716A, on nitric oxide (NO) and EDHF-mediated
relaxation in precontracted rings of porcine coronary, rabbit carotid and
mesenteric arteries. 2. In rings of mesenteric artery HU 210 and delta9-THC
induced endothelium- and cyclo-oxygenase-independent relaxations which were
sensitive to SR 141716A. Anandamide (0.03-30 microM) induced a slowly developing,
endothelium-independent relaxation which was abolished by diclofenac and was
therefore mediated by cyclo-oxygenase product(s). None of the CB1 agonists tested
affected the tone of precontracted rings of rabbit carotid or porcine coronary
artery. 3. In endothelium-intact segments, HU 210, delta9-THC and anandamide did
not affect NO-mediated responses but under conditions of continuous NO
synthase/cyclo-oxygenase blockade, significantly inhibited acetylcholine and
bradykinin-induced relaxations which are attributed to the production of EDHF.
The effects of HU 210 and delta9-THC were not observed when experiments were
performed in the presence of SR 141716A suggesting the involvement of the CB1
receptor. 4. In a patch clamp bioassay of EDHF production, HU 210 decreased the
EDHF-mediated hyperpolarization of detector smooth muscle cells when applied to
the donor segment but was without effect on the membrane potential of detector
cells. The inhibition of EDHF production was unrelated to alterations in Ca2+
signalling or cytochrome P450 activity. 5. These results suggest that the
activation of endothelial CB1 receptors appears to be negatively coupled to the
production of EDHF.
PMID- 10193776
TI - Effect of cerivastatin sodium, a new inhibitor of HMG-CoA reductase, on plasma
lipid levels, progression of atherosclerosis, and the lesional composition in the
plaques of WHHL rabbits.
AB - 1. The aim of this study was to examine whether cerivastatin sodium, a new
inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, affects
the lesional composition of spontaneously developed atherosclerosis due to
hypercholesterolaemia and delays progression of the lesions. 2. We administered
cerivastatin to 2-month-old WHHL rabbits, a low-density lipoprotein receptor
deficient animal model, at a dose of 0.6 mg kg(-1) day(-1) for 32 weeks. We
examined the plasma lipid levels, the severity of atherosclerosis, and
composition of atherosclerotic lesions. Lesional composition was determined using
immunohistostaining for macrophages and smooth muscle cells, and Azan-Mallory
staining for collagen fibres and extracellular lipid deposits. 3. Compared to the
control group, the plasma cholesterol levels were decreased in the treated group
by 39% (12.7+/-0.6 mmol L(-1) versus 20.9+/-1.0 mmol L(-1), P<0.001).
Atherosclerosis was suppressed by about 37% as measured by the thickness of the
aortic lesions (158+/-13 microm versus 250+/-15 microm, P<0.001), and by 28% as
measured by coronary stenosis (62.7+/-11.4 versus 86.9+/-12.2, P<0.05). In the
cerivastatin group, regarding the per cent areas of lesional components in the
lesion area, the macrophages (21.0+/-1.5% versus 27.9+/-1.9%, P<0.01) and
extracellular lipid deposits (3.2+/-0.4% versus 5.1+/-0.4%, P<0.001) were
decreased in the aortic lesions, and the per cent area of macrophages in the
coronary lesions was also decreased (4.9+/-1.4% versus, 11.6+/-2.4%. P<0.05). The
per cent area of smooth muscle cells and collagen fibres did not significantly
decrease. 4. These results indicate that cerivastatin contributed to the plaque
stabilization and delayed progression of early atherosclerosis in young WHHL
rabbits, in addition to the potent hypolipidemic effects.
PMID- 10193777
TI - A2B adenosine receptors mediate relaxation of the pig intravesical ureter:
adenosine modulation of non adrenergic non cholinergic excitatory
neurotransmission.
AB - 1. The present study was designed to characterize the adenosine receptors
involved in the relaxation of the pig intravesical ureter, and to investigate the
action of adenosine on the non adrenergic non cholinergic (NANC) excitatory
ureteral neurotransmission. 2. In U46619 (10(-7) M)-contracted strips treated
with the adenosine uptake inhibitor, nitrobenzylthioinosine (NBTI, 10(-6) M),
adenosine and related analogues induced relaxations with the following potency
order: 5'-N-ethylcarboxamidoadenosine (NECA) = 5'-(N-cyclopropyl)
carboxamidoadenosine (CPCA) = 2-chloroadenosine (2-CA) > adenosine >
cyclopentyladenosine (CPA) = N6-(3-iodobenzyl)-adenosine-5'-N-methylcarboxamide
(IB-MECA) = 2-[p-(carboxyethyl)-phenylethylamino]-5'-N-ethylcarboxamidoaden os
ine (CGS21680). 3. Epithelium removal or incubation with indomethacin (3 x 10(-6)
M) and L-N(G)-nitroarginine (L-NOARG, 3 x 10(-5) M), inhibitors of prostanoids
and nitric oxide (NO) synthase, respectively, failed to modify the relaxations to
adenosine. 4. 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 10(-8) M) and 4-(2-[7
amino-2-(2-furyl) [1,2,4]-triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol
(ZM 241385, 3 x 10(-8) M and 10(-7) M), A1 and A2A receptor selective
antagonists, respectively, did not modify the relaxations to adenosine or NECA. 8
phenyltheophylline (8-PT, 10(-5) M) and DPCPX (10(-6) M), which block A1/A2
receptors, reduced such relaxations. 5. In strips treated with guanethidine (10(
5) M), atropine (10(-7) M), L-NOARG (3 x 10(-5) M) and indomethacin (3 x 10(-6)
M), both electrical field stimulation (EFS, 5 Hz) and exogenous ATP (10(-4) M)
induced contractions of preparations. 8-PT (10(-5) M) increased both
contractions. DPCPX (10(-8) M), NECA (10(-4) M), CPCA, (10(-4) M) and 2-CA (10(
4) M) did not alter the contractions to EFS. 6. The present results suggest that
adenosine relaxes the pig intravesical ureter, independently of prostanoids or
NO, through activation of A2B-receptors located in the smooth muscle. This
relaxation may modulate the ureteral NANC excitatory neurotransmission through a
postsynaptic mechanism.
PMID- 10193778
TI - The effects of phosphodiesterase type 4 inhibitors on tumour necrosis factor
alpha and leukotriene B4 in a novel human whole blood assay.
AB - 1. The aim of this study was to assess the inhibitory activities of
phosphodiesterase type 4 (PDE4) inhibitors on tumour necrosis factor-alpha (TNF
alpha) and leukotriene B4 (LTB4) production in a novel human whole blood assay.
2. Lipopolysaccharide (LPS) stimulation of human whole blood caused a time
dependent increase in TNF-alpha and prostaglandin E2 (PGE2) plasma levels.
Inhibition of LPS-induced TNF-alpha by the selective PDE4 inhibitor RP73401 was
proportionally enhanced with endogenous PGE2 (maximal after 24 h). In contrast,
blocking endogenous PGE2 production with indomethacin in blood stimulated with
LPS for 24 h decreased the potency of RP73401 to that observed with a 4 h LPS
incubation. 3. Non-selective and selective PDE4 inhibitors showed greater
inhibition of LPS-induced TNF-alpha after 24 h compared to 4 h. Stereoselectivity
was only achieved in the 24 h method. 4. LPS-stimulation of whole blood for
either 30 min or 24 h followed by N-formyl-Met-Leu-Phe (fMLP) activation resulted
in low plasma LTB4 levels. Combination of both treatments resulted in a greater
than 7 fold increase in plasma LTB4 levels. Inhibition of the double LPS and fMLP
activated LTB4 production was observed with non-selective and PDE4-selective
inhibitors. Their LTB4 inhibitory potencies were similar to that observed in the
24 h LPS-induced TNF-alpha assay. Thus, stimulation of human whole blood with two
LPS stimulations followed by fMLP gives rise to both TNF-alpha and LTB4 and their
inhibition by various compounds can be assessed in the same blood sample. 5.
Calcium ionophore (A23187) stimulation of whole blood resulted in plasma LTB4
levels similar to the double LPS and fMLP method. Inhibition of A23187-induced
LTB4 biosynthesis was also achieved by PDE4-selective inhibitors as well as the
direct 5-lipoxygenase (5-LO) inhibitor L-739,010. 6. These results confirm the
anti-inflammatory properties of PDE4 inhibitors. Thus, this novel human whole
blood can be used to assess the biochemical efficacy of PDE4 inhibitors in human
subjects.
PMID- 10193779
TI - Influence of TASP-V, a novel neuropeptide Y (NPY) Y2 agonist, on nasal and
bronchial responses evoked by histamine in anaesthetized pigs and in humans.
AB - 1. In nine anaesthetized pigs we have studied the influence of intranasal or
intrabronchial pretreatment with TASP-V, a neuropeptide Y (NPY) Y2 agonist formed
by the attachment of NPY 21-36 to a template-assembled synthetic peptide (TASP),
on the functional responses to subsequent intranasal or intrabronchial histamine
challenge. 2. In a parallel study, subjective and objective nasal airway
resistance (NAR) increase following intranasal histamine challenge was evaluated
in 11 healthy volunteers after TASP-V or placebo pretreatment. 3. In pigs,
increase in sphenopalatine blood flow induced by histamine dihydrochloride nasal
spray (0.25 mg kg(-1) in 3 ml of saline) was significantly reduced by 65%
(P<0.05) following intranasal pretreatment with 10 microg kg(-1) of TASP-V.
Bronchoconstriction induced by histamine dihydrochloride nebulization (0.5 mg kg(
1) in 3 ml of saline) was significantly attenuated by 25 and 55% following
aerosolized pretreatment with TASP-V analogue at 10 and 20 microg kg(-1),
respectively. 4. In healthy volunteers, objective increase in NAR and reduction
in nasal minimal cross section area (MCSA) induced by intranasal spray of
histamine dihydrochloride (15 microg kg(-1) in 200 microl of saline) were
significantly attenuated by 50% following local pretreatment with 1.275 microg
kg(-1) of TASP-V when compared with saline. 5. It is concluded that intranasal or
intrabronchial pretreatment with TASP-V reduced nasal obstruction and
bronchoconstriction evoked by histamine challenge in the pig. In healthy human
volunteers, this agent attenuated NAR increase and MCSA reduction induced by
intranasal application of histamine.
PMID- 10193780
TI - Effect of low-dose treatment with selegiline on dopamine transporter (DAT)
expression and amphetamine-induced dopamine release in vivo.
AB - 1. Chronic treatment with low doses of the selective monoamine oxidase (MAO) type
B inhibitors selegiline [(-)-deprenyl] and rasagiline, causes elevation in
extracellular level of 3,4-dihydroxyphenylethylamine (dopamine) in the rat
striatum in vivo (Lamensdorf et al., 1996). The present study was carried out to
determine whether this effect of selegiline could be the result of an inhibition
of the high-affinity dopamine neuronal transport process. 2. Changes in activity
of the dopamine transporter (DAT) in vivo following selegiline treatment were
evaluated indirectly by microdialysis technique in the rat, from the change in
striatal dopamine extracellular concentration following systemic amphetamine
administration (4 mg kg(-1), i.p.). Striatal levels of the DAT molecule were
determined by immunoblotting. Uptake of [3H]-dopamine was determined in
synaptosomes from selegiline-treated animals. 3. Amphetamine-induced increase in
striatal extracellular dopamine level was attenuated by one day and by chronic
(21 days) treatment with selegiline (0.25 mg kg(-1), s.c.). 4. Striatal levels of
DAT were elevated after 1 and 21 days treatment with selegiline, but were not
affected by clorgyline, rasagiline, nomifensine or amphetamine. 5. The increase
in DAT expression, and attenuation of amphetamine-induced dopamine release, were
not accompanied by a change in [3H]-dopamine uptake in synaptosomes of selegiline
treated animals. 6. The results suggest that a reversible inhibition of dopamine
uptake occurs following chronic low dose selegiline treatment in vivo which may
be mediated by an increase in endogenous MAO-B substrates such as 2
phenylethylamine, rather than by the inhibitor molecule or its metabolites.
Increased DAT expression appears to be a special property of the selegiline
molecule, since it occurs after one low dose of selegiline, and is not seen with
other inhibitors of MAO-A or MAO-B. The new DAT molecules formed following
selegiline treatment appear not to be functionally active.
PMID- 10193781
TI - The inhibition of nicotine-evoked relaxation of the guinea-pig isolated basilar
artery by some analgesic drugs and progesterone.
AB - 1. The purpose of this study was to investigate the mechanism of nicotine-evoked
relaxation of the guinea-pig isolated basilar artery and to study the effects of
drugs associated with the aetiology or treatment of migraine on the nicotine
response. 2. The guinea-pig isolated basilar artery, pre-contracted with
prostaglandin F2alpha (PGF2alpha), in the presence of atropine (3 microM) and
guanethidine (3 microM), relaxed on addition of nicotine (0.1 mM) in
approximately 50% of preparations. The responses to nicotine were of short
duration and blocked in preparations pre-treated for 10 min with capsaicin (1
microM) and are therefore probably a consequence of the stimulation of trigeminal
C fibre terminals. 3. Responses to nicotine were reduced in the presence of 5
carboxamidotryptamine, 5-hydroxytryptamine and sumatriptan in that order of
potency. This is consistent with a 5-HT1 receptor mechanism. These agonists
evoked small additional contractions in vessels pre-contracted with PGF2alpha. 4.
Indomethacin (0.3-10 microM), aspirin (10-30 microM), and nitro-L-arginine methyl
ester (L-NAME, 0.1 mM) reduced nicotine-evoked relaxation of the basilar artery,
suggesting the involvement of both nitric oxide and cyclo-oxygenase products in
this response. 5. Progesterone (1 microM) markedly reduced the response to
nicotine, a possible reflection of the ion channel blocking activity of high
concentrations of this compound. 6. The guinea-pig basilar artery is a
preparation in which the effects of drugs on responses to stimulation of
trigeminal nerve terminals can be studied in vitro and may thus be of interest in
assessing the actions of drugs used in treatment of headache.
PMID- 10193782
TI - Dual coupling of heterologously-expressed rat P2Y6 nucleotide receptors to N-type
Ca2+ and M-type K+ currents in rat sympathetic neurones.
AB - 1. The P2Y6 receptor is a uridine nucleotide-specific G protein-linked receptor
previously reported to stimulate the phosphoinositide (PI) pathway. We have
investigated its effect in neurones, by micro-injecting its cRNA into dissociated
rat sympathetic neurones and recording responses of N-type Ca2+ (I(Ca(N))) and M
type K+ (I(K(M))) currents. 2. In P2Y6 cRNA-injected neurones, UDP or UTP
produced a voltage-dependent inhibition of I(Ca(N)) by approximately 53% in whole
cell (disrupted-patch) mode and by 73% in perforated-patch mode; no inhibition
occurred in control cells. Mean IC50 values (whole-cell) were: UDP, 5.9+/-0.3 nM;
UTP, 20+/-1 nM. ATP and ADP (1 microM) had no significant effect. Pertussis toxin
(PTX) substantially (approximately 60%) reduced UTP-mediated inhibition in
disrupted patch mode but not in perforated-patch mode. 3. Uridine nucleotides
also inhibited I(K(M)) in P2Y6 cRNA-injected cells (by up to 71% at 10 microM
UTP; perforated-patch). Mean IC50 values were: UDP, 30+/-3 nM; UTP, 115+/-12 nM.
ATP (10 microM) again had no effect. No significant inhibition occurred in
control cells. Inhibition was PTX-resistant. 4. Thus, the P2Y6 receptor, like the
P2Y2 subtype studied in this system, couples to both of these two neuronal ion
channels through at least two different G proteins. However, the P2Y6 receptor
displays a much higher sensitivity to its agonists than the P2Y2 receptor in this
expression system and higher than previously reported using other expression
methods. The very high sensitivity to both UDP and UTP suggests that it might be
preferentially activated by any locally released uridine nucleotides.
PMID- 10193783
TI - Aryl propanolamines: comparison of activity at human beta3 receptors, rat beta3
receptors and rat atrial receptors mediating tachycardia.
AB - 1. The in vitro activity of four aryl propanolamines was compared to two
prototypic beta3 receptor agonists, CGP 12177 and CL316243 at the human beta3
receptor, the rat beta3 receptor in the stomach fundus and receptors mediating
atrial tachycardia. 2. L-739,574 was the most potent (EC50 = 9 nM) and selective
agonist at the human beta3 receptor with high maximal response (74% of the
maximal response to isoproterenol). 3. A phenol-biaryl ether analogue possessed
modest affinity for the human beta3 receptor (EC50 = 246 nM), but was highly
efficacious with a maximal response 82% of the maximal response to isoproterenol.
The other derivatives were intermediate in potency with low maximal responses. 4.
These agonists at the human beta3 receptor did not activate the rat beta3
receptor in the rat stomach fundus. In fact, the aryl propanolamines (10(-6) M)
inhibited CL316243-induced activation of the rat beta3 receptor. Thus, agonist
activity at the human beta3 receptor translated into antagonist activity at the
rat beta3 receptor. 5. L739,574 and the phenol biaryl ether increased heart rate
via beta1 receptors. 6. Although CGP12177 produced atrial tachycardia, neither
the indole sulphonamide nor biphenyl biaryl ether did, although both had high
affinity for the human beta3 receptor. Thus, the atrial tachycardic receptor was
not identical to the human beta3 receptor. 7. These studies (a) characterized
four aryl propanolamines with high affinity at the human beta3 receptor, (b)
found that they were antagonists at the rat beta3 receptor, an observation with
profound implications for in vivo rat data, and (c) established that the rodent
atrial non-beta1, beta2 or beta3 tachycardic receptor was also unrelated to the
human beta3 receptor.
PMID- 10193784
TI - Effects of nicorandil as compared to mixtures of sodium nitroprusside and
levcromakalim in isolated rat aorta.
AB - 1. The contribution of the relaxant mechanisms of nicorandil (NIC) were analysed
by comparing its effects with those of sodium nitroprusside (SNP), levcromakalim
(LEM) and mixtures (1:10, 1:30 and 1:100) of SNP:LEM in isolated endothelium
denuded rat aorta. 2. In rings precontracted with KCl (25 mM), the relative
inhibitory potency of the soluble guanylate cyclase inhibitor ODQ and the K(ATP)
channel inhibitor glibenclamide (GLI) on SNP:LEM mixtures showed a good
correlation with the relative proportion of SNP and LEM in the mixtures.
Furthermore, the degree of the inhibition by ODQ and GLI of the effects of the
1:30 SNP:LEM mixture varied as a function of the relative potency of SNP and LEM
in KCl-, noradrenaline- (NA) or NA plus nifedipine-treated arteries. 3. The
inhibitory effects of ODQ, GLI and ODQ plus GLI on NIC-induced relaxation was
similar to that for the 1:30 SNP:LEM mixture in NA plus nifedipine-contracted
arteries, but the inhibition of GLI or ODQ plus GLI was smaller in KCl-contracted
arteries. 4. In conclusion, the relative importance of activation of the cyclic
GMP pathway and K(ATP) channel opening in mixtures of SNP and LEM could be
predicted by the proportion of the drugs in the mixtures and by the relative
potency of SNP vs LEM in different experimental conditions. Furthermore, the
present results suggest that besides these two mechanisms, a third ODQ- and GLI
insensitive mechanism, possibly involving Ca2+ channel blockade, also
participates in the relaxant effects of NIC in KCl-induced contractions.
PMID- 10193785
TI - Investigation of the inhibitory effects of homocysteine and copper on nitric
oxide-mediated relaxation of rat isolated aorta.
AB - 1. Elevated plasma levels of homocysteine (HC) and copper have both been
associated with the development of inflammatory vascular diseases, such as
atherosclerosis. In this study, the effects of a combination of HC and copper on
nitric oxide (NO)-mediated relaxation of isolated rat aortic rings were
investigated. 2. Exposure to HC (10-100 microM; 30 min) had no effect on
relaxation to acetylcholine (ACh; 0.01-10 microM, n=4). Pre-incubation of aortic
rings with a higher concentration of HC for an extended period (1 mM; 180 min)
significantly inhibited endothelium-dependent relaxation (n=4), but this
inhibition was prevented by the presence of the copper chelator bathocuprione (10
microM, 180 min, n=6). 3. Exposure to HC (100 microM) and copper (10-100 microM;
30 min) caused a copper concentration-dependent inhibition of endothelium
dependent relaxation (n=4). This inhibitory effect was reduced in the presence of
either superoxide dismutase (SOD; 100 u ml(-1); n=4) or catalase (100 u ml(-1);
n=4), and further reduced by the presence of both enzymes (n=5). 4. HC and copper
(100 microM; 30 min) significantly inhibited endothelium-independent relaxation
to glyceryl trinitrate (0.01-10 microM; n=8). In contrast, HC (1 mM), alone or in
combination with copper (100 microM), did not inhibit relaxation to the
endothelium-independent relaxant sodium nitroprusside (0.01-10 microM; n=4). 5.
These data indicate that the presence of copper greatly enhances the inhibitory
actions of HC on NO-mediated relaxation of isolated aortic rings. The reduction
of inhibition by catalase and SOD indicates a possible role for copper-catalyzed
generation of superoxide and hydrogen peroxide leading to an increased
inactivation or decreased production of endothelium-derived NO.
PMID- 10193787
TI - Characterization of high affinity neurotensin receptor NTR1 in HL-60 cells and
its down regulation during granulocytic differentiation.
AB - 1. We investigated responses to neurotensin in human promyelocytic leukaemia HL
60 cells. 2. Neurotensin increased the cytosolic calcium concentration ([Ca2+]i)
in a concentration-dependent manner and also produced inositol 1,4,5
trisphosphate (InsP3). 3. Among the tested neurotensin analogues, neurotensin 8
13, neuromedin-N, and xenopsin also increased [Ca2+]i, whereas neurotensin 1-11
and neurotensin 1-8 did not elicit detectable responses. 4. SR48692, an
antagonist of NTR1 neurotensin receptors, blocked the neurotensin-induced [Ca2+]i
increase, whereas levocabastine, which is known as an NTR2 neurotensin receptor
antagonist, did not attenuate the neurotensin-evoked effect. 5. The expression of
NTR1 neurotensin receptors was confirmed by Northern blot analysis and reverse
transcriptase-polymerase chain reaction (RT-PCR). 6. During 1.25%
dimethylsulfoxide (DMSO)-triggered granulocytic differentiation of HL-60 cells,
the neurotensin-induced [Ca2+]i rise became gradually smaller and completely
disappeared 4 days after treatment with DMSO. The mRNA level for neurotensin
receptors was also decreased after differentiation. 7. The results show that HL
60 cells express NTR1 neurotensin receptors and suggest that granulocytic
differentiation involves transcriptional regulation of the receptors resulting in
down-regulation of the neurotensin-induced signalling.
PMID- 10193786
TI - Cell-specific coupling of PGE2 to different transduction pathways in arginine
vasopressin- and glucagon-sensitive segments of the rat renal tubule.
AB - 1. The aim of the present study was to investigate the transduction pathways
elicited by prostaglandin E2 (PGE2) to inhibit hormone-stimulated adenosine 3':5'
cyclic monophosphate (cyclic AMP) accumulation in the outer medullary collecting
duct (OMCD) and medullary thick ascending limb (MTAL) microdissected from the rat
nephron. 2. In the OMCD, 0.3 microM PGE2 and low concentrations of Ca2+
ionophores (10 nM ionomycin or 50 nM A23187) inhibited by about 50% a same pool
of arginine vasopressin (AVP)-stimulated cyclic AMP content through a same
process insensitive to Bordetella pertussis toxin (PTX). 3. Sulprostone, an
agonist of the EP1/EP3 subtypes of the PGE2 receptor, decreased AVP-dependent
cyclic AMP accumulation in OMCD and MTAL samples. The concentration eliciting
half-maximal inhibition was of about 50 nM in OMCD and 0.1 nM in MTAL. 4. In
MTAL, 1 nM sulprostone and PGE2 inhibited by about 90% a same pool of AVP
dependent cyclic AMP content through a PTX-sensitive, Ca2+ -independent pathway.
5. In the OMCD, PGE2 decreased by about 50% glucagon-dependent cyclic AMP
synthesis by a process sensitive to PTX and Ca2+ -independent. Sulprostone 1 nM
induced the same level of inhibition. 6. These results demonstrate that PGE2
decrease hormone-dependent cyclic AMP accumulation through a G(alpha)i-mediated
inhibition of adenylyl cyclase activity in MTAL cells and glucagon-sensitive
cells of the OMCD or through a PTX-insensitive increase of intracellular Ca2+
concentration in AVP-sensitive cells of the OMCD.
PMID- 10193788
TI - Distinction between surmountable and insurmountable selective AT1 receptor
antagonists by use of CHO-K1 cells expressing human angiotensin II AT1 receptors.
AB - 1. CHO-K1 cells that were stably transfected with the gene for the human AT1
receptor (CHO-AT1 cells) were used for pharmacological studies of non-peptide AT1
receptor antagonists. 2. In the presence of 10 mM LiCl, angiotensin II caused a
concentration-dependent and long-lasting increase of inositol phosphates
accumulation with an EC50 of 3.4 nM. No angiotensin II responses are seen in wild
type CHO-K1 cells. 3. [3H]-Angiotensin II bound to cell surface AT1 receptors
(dissociates under mild acidic conditions) and is subject to rapid
internalization. 4. Non-peptide selective AT1 antagonists inhibited the
angiotensin II (0.1 microM) induced IP accumulation and the binding of [3H]
angiotensin II (1 nM) with the potency order: candesartan > EXP3174 > irbesartan
> losartan. Their potencies are lower in the presence of bovine serum albumin. 5.
Preincubation with the insurmountable antagonist candesartan decreased the
maximal angiotensin II induced inositol phosphate accumulation up to 94% and,
concomitantly, decreased the maximal binding capacity of the cell surface
receptors. These inhibitory effects were half-maximal for 0.6 nM candesartan and
were attenuated by simultaneous preincubation with 1 microM losartan indicating a
syntopic action of both antagonists. 6. Losartan caused a parallel rightward
shift of the angiotensin II concentration-response curves and did not affect the
maximal binding capacity. EXP3174 (the active metabolite of losartan) and
irbesartan showed a mixed-type behavior in both functional and binding studies.
7. Reversal of the inhibitory effect was slower for candesartan as compared with
EXP3174 and irbesartan and it was almost instantaneous for losartan, suggesting
that the insurmountable nature of selective AT1 receptor antagonists in
functional studies was related to their long-lasting inhibition.
PMID- 10193790
TI - New insights into the molecular mechanism of the action of diuretics.
PMID- 10193789
TI - Evidence for novel caffeine and Ca2+ binding sites on the lobster skeletal
ryanodine receptor.
AB - 1. The effects of Ca2+, ATP and caffeine on the gating of lobster skeletal muscle
ryanodine receptors (RyR) was investigated after reconstitution of the channels
into planar phospholipid bilayers and by using [3H]-ryanodine binding studies. 2.
The single channel studies reveal that the EC50 (60 microM) for activation of the
lobster skeletal RyR by Ca2+ as the sole ligand is higher than for any other
isoform of RyR studied. 3. Inactivation of the channel by Ca2+ (EC50 = 1 mM)
occurs at concentrations slightly higher than those required to inactivate
mammalian skeletal RyR (RyR1) but lower than those required to inactivate
mammalian cardiac RyR (RyR2). 4. Lifetime analysis demonstrates that cytosolic
Ca2+, as the sole activating ligand, cannot fully open the lobster skeletal RyR
(maximum Po approximately 0.2). The mechanism for the increase in open
probability (Po) is an increase in both the frequency and the duration of the
open events. 5. ATP is a very effective activator of the lobster RyR and can
almost fully open the channel in the presence of activating cytosolic [Ca2+]. In
the presence of 700 microM Ca2+, 1 mM ATP increased Po to approximately 0.8. 6.
Caffeine, often used as a tool to identify the presence of RyR channels, is
relatively ineffective and cannot increase Po above the level that can be
attained with Ca2+ alone. 7. The results reveal that caffeine increases Po by a
different mechanism to that of cytosolic Ca2+ demonstrating that the mechanism
for channel activation by caffeine is not 'sensitization' to cytosolic Ca2+. 8.
By studying the mechanisms involved in the activation of the lobster RyR we have
demonstrated that the channel responds in a unique manner to Ca2+ and to
caffeine. The results strongly indicate that these ligand binding sites on the
channel are different to those on mammalian isoforms of RyR.
PMID- 10193791
TI - Therapeutic uses of heparinoids in renal disease patients.
PMID- 10193792
TI - Cyst formation in ADPKD: new insights from natural and targeted mutants.
PMID- 10193793
TI - NIMA (non-inherited maternal antigens) versus NIPA (non-inherited paternal
antigens) and tolerance of human kidney graft.
PMID- 10193794
TI - Haemolytic-uraemic syndrome--the experience in Argentina.
PMID- 10193795
TI - The diagnostic trash bin of focal and segmental glomerulosclerosis--an effort to
provide rational clinical guidelines.
PMID- 10193796
TI - Abnormal arachidonic acid content of membrane phospholipids--the unifying
hypothesis for the genesis of hypercalciuria and hyperoxaluria in idiopathic
calcium nephrolithiasis.
PMID- 10193797
TI - Advantages of Ang II receptor blockade over ACE inhibition with respect to
suppression of sympathetic activity: heartening news for the kidney?
PMID- 10193798
TI - Duration of dialysis sessions--was Hegel right?
PMID- 10193799
TI - Recurrence of glomerulonephritis following renal transplantation. Scientific
Advisory Board of the ERA-EDTA Registry. European Renal Association-European
Dialysis and Transplant Association.
PMID- 10193800
TI - Factors influencing second renal allograft survival. Scientific Advisory Board of
the ERA-EDTA Registry. European Renal Association-European Dialysis and
Transplant Association.
PMID- 10193801
TI - Renal transplantation for uncommon diseases. Scientific Advisory Board of the ERA
EDTA Registry. European Renal Association-European Dialysis and Transplant
Association.
PMID- 10193802
TI - A sensitive and specific ELISA for plasma pentosidine.
AB - BACKGROUND: Advanced glycation end products are formed by non-enzymatic glycation
and oxidation reaction. Pentosidine is a well-known and characterized structure
among them, and has been implicated in the pathogenesis of complications
associated with chronic renal failure and long-term dialysis, such as dialysis
related amyloidosis and atherosclerosis. METHODS: We established a highly
sensitive and specific competitive enzyme-linked immunosorbent assay (ELISA) for
plasma pentosidine and applied it to large numbers of plasma samples including
haemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) patients.
We compared their plasma pentosidine levels determined by the competitive ELISA
with those determined by high-performance liquid chromatographic (HPLC) assay
currently used. RESULTS: The plasma pentosidine levels determined by the ELISA
were correlated well with those determined by sophisticated instrumental HPLC
assay, both in non-diabetic and diabetic dialysis patients. Both analyses yielded
comparable results, with over 8-fold higher plasma pentosidine levels in HD and
CAPD patients, irrespective of the presence or absence of diabetes, as compared
to normal subjects and non-uraemic diabetic patients. CONCLUSIONS: The
competitive ELISA will provide a rapid and convenient determination of plasma
pentosidine content and thus be useful to assess the carbonyl stress in uraemic
patients.
PMID- 10193803
TI - Dopamine depolarizes podocytes via a D1-like receptor.
AB - BACKGROUND: Dopamine influences glomerular haemodynamics and dopamine receptors
have been demonstrated in the glomerulus, but little is known about the cellular
effects of dopamine in glomerular cells. The aim of this study was to investigate
the influence of dopamine on the cellular functions of podocytes. METHODS: The
effect of dopamine on membrane voltage was investigated in differentiated mouse
podocytes. The membrane voltage was measured using the patch clamp technique.
Reverse transcribed-polymerase chain reaction (RT-PCR) studies were performed to
investigate the expression of dopamine receptor mRNA in mouse glomeruli and
podocytes. RESULTS: The addition of dopamine (100 nM-1000 microM) caused a
concentration-dependent depolarization of podocytes (EC50 is approximate to 10
microM). Like dopamine, the selective agonist of the D1-like receptor, SKF 82958,
depolarized podocytes in a concentration-dependent manner. (EC50 is approximate
to 50 microM). SKF 82958 stimulated a time-and concentration-dependent
accumulation of cyclic adenosine 3',5'-monophosphate (cAMP) in podocytes (EC50 is
approximate to microM). RT-PCR studies with primers derived from mouse sequences
amplified mouse mRNA for the D1-like and the D2-like receptor in glomeruli, which
were obtained by the sieve technique, whereas only mRNA for the D1-like receptor
was detected in cultured mouse podocytes. CONCLUSION: The data indicate that
dopamine induces a cAMP-dependent depolarization via a D1-like receptor in
podocytes.
PMID- 10193804
TI - Functional and structural properties of urinary tissue factor.
AB - BACKGROUND: We have previously explored the clinical significance of urinary
tissue factor (uTF) in patients with glomerulonephritis (GN) and malignancy.
However, the functional and structural properties and putative cell of origin of
uTF are poorly documented. In these studies we investigate these aspects of uTF.
METHODS: Functional and structural properties of uTF were investigated using a
one stage kinetic chromogenic assay, an enzyme-linked immunoabsorbent assay
(ELISA) and transmission electron microscopy (TEM) on urine samples collected
from healthy controls (n=69). The distribution of uTF and anionic phospholipid in
the kidney were studied in sections from normal areas of nephrectomy specimens,
using an immunoperoxidase technique. These were stained for tissue factor (TF)
antigen and recombinant Annexin V. RESULTS: We found uTF to be present on
subcellular particles as visualized by TEM. These particles contained anionic
phospholipid as evidenced by binding to Annexin V fluorescein isothiocyanate
(FITC). Although TF is present in urine in a functional and antigenic form no
association was observed between the two. Using immunoperoxidase-based
techniques, the cytoplasm of both distal and proximal tubules (but not glomerular
cells) was positive for TF antigen and Annexin V. CONCLUSION: uTF is found on
subcellular particles which provide lipid for its functional activity. Both uTF
and its associated vesicles are found in the renal tubular cells.
PMID- 10193805
TI - Human recombinant erythropoietin inhibits interleukin-1beta-stimulated nitric
oxide and cyclic guanosine monophosphate production in cultured rat vascular
smooth-muscle cells.
AB - BACKGROUND: Recently rat vascular smooth-muscle cells (VSMC) have been shown to
possess Epo receptor, and respond to various cytokines for producing nitric oxide
(NO). In the present study we examined the effect of pharmacological dose of
human recombinant erythropoietin (rHuEpo) on the IL-1beta-induced NO and cGMP
production as well as inducible nitric oxide synthase (iNOS) in cultured rat
VSMC. METHODS: Nitrite, a stable metabolite of NO, and intracellular cGMP
contents were assayed by Griess method and enzyme immunoassay. iNOS mRNA
expression was analysed by Northern blotting. RESULTS: RHuEpo inhibited IL-1beta
induced nitrite production in a dose- and time-dependent manner with concomitant
changes of intracellular cGMP contents. On the other hand, rHuEpo did not inhibit
atrial natriuretic peptide- (ANP) or sodium nitroprusside (SNP)-induced nitrite
and cGMP production at all. While rHuEpo inhibited IL-1beta-induced iNOS mRNA
expression, rHuEpo vehicle did not affect IL-1beta-induced iNOS mRNA expression.
CONCLUSIONS: It is suggested that a pharmacological dose of rHuEpo inhibits IL
1beta-induced NO and cGMP production as well as iNOS mRNA expression, presumably
via the Epo receptor.
PMID- 10193806
TI - Rapid recovery of plasma ionized calcium after acute induction of hypocalcaemia
in parathyroidectomized and nephrectomized rats.
AB - BACKGROUND: Plasma ionized calcium (Ca2+) is extremely tightly regulated in
normal mammals. Even a small decline in Ca2+ is followed by a fast and steep
increase of the parathyroid hormone (PTH) secretion and the current understanding
of the calcium homeostasis indicates that PTH is the main factor responsible for
this tight minute-to-minute regulation of the normal plasma Ca2+ concentration.
However, experiments from our laboratory and some clinical experiences points
towards the existence of factors, other than PTH, involved in the rapid minute-to
minute calcium homeostasis. Thus, the aim of the present study was to examine
whether PTH plays an important role in the rapid upregulation of plasma Ca2+
after induction of hypocalcaemia in the rat. METHODS AND RESULTS: I.
Parathyroidectomy (PTX) was performed in seven rats; 60 min later no PTH was
detectable in the circulation. Then by a brief infusion of EGTA plasma Ca2+ was
reduced from 1.26+/-0.02 to 0.86+/-0.02 mmol/l, P<0.001. Despite there being no
PTH in the circulation plasma Ca2+ increased significantly to 0.97+/-0.02 mmol/l
already 10 min after discontinuation of the EGTA infusion, P<0.04, and plasma
Ca2+ was normalized within another 2 h. II. To evaluate a possible role of renal
Ca2+ handling in the rapid upregulation of plasma Ca2+ a group of eight rats had
acute PTX and bilateral nephrectomy (NX) performed; 60 min later plasma Ca2+ was
reduced from 1.18+/-0.01 to 0.86+/-0.02 mmol/l by an EGTA infusion. Despite there
being no PTH and no kidneys present plasma Ca2+ increased significantly already
10 min after discontinuation of EGTA to 0.96+/-0.02 mmol/l, P<0.02. After another
1.5 h the plasma Ca2+ reached the levels of the PTX/NX control rats. III. In
order to exclude a possible action of receptor-bound PTH, which may have lasted
for more than 1 h, seven rats were PTX 24 h before the induction of
hypocalcaemia. Basal plasma Ca2+ was significantly reduced to 1.07+/-0.01 mmol/l,
P<0.01. Then plasma Ca2+ was further reduced to 0.79+/-0.03 mmol/l by EGTA. Ten
minutes after discontinuing EGTA plasma Ca2+ increased to 0.91+/-0.02 mmol/l,
P<0.03 and 60 min later plasma Ca2+ reached the level of the control PTX rats.
Normal rats with intact parathyroid glands had an exactly similar response of
plasma Ca2+ to EGTA as that of 24 h PTX rats, but at significantly higher levels
of plasma Ca2+ with a fall from 1.28+/-0.01 to 0.96+/-0.03 mmol/l and again a
significant increase of plasma Ca2+ to 1.13+/-0.03 (P<0.001) 10 min after
discontinuation of EGTA. After another hour basal levels were reached.
CONCLUSIONS: Despite there being no PTH in the circulation a rapid increase of
plasma Ca2+ occurs immediately after a brief induction of hypocalcaemia. The
kidneys are not responsible for this phenomenon. The present results suggest the
existence of a mechanism other than the effect of PTH, which is responsible for
the rapid minute-to-minute regulation of plasma Ca2+ in the rat.
PMID- 10193807
TI - Effects of niceritrol on faecal and urinary phosphate excretion in normal rats.
AB - BACKGROUND: Phosphate binders such as aluminium hydroxide and calcium carbonate
have several side-effects so that they are not ideal for clinical use. Recently
we reported that administration of niceritrol at 750 mg/day to patients with HDL
hypocholesterolaemia undergoing dialysis decreased the serum phosphate
concentration. To clarify the mechanism of reduction of the serum phosphate
concentration by niceritrol in patients undergoing dialysis, the effects of
niceritrol on faecal and urinary phosphate excretion were examined in normal
rats. METHODS: Niceritrol suspension in 5% gum arabic was administered for 4 days
in normal rats. Faeces and urine were collected in metabolic cage and analysed
for phosphate content. RESULTS AND CONCLUSIONS: Faecal phosphate excretion
significantly increased in the groups with administration of 100 and 500 mg/kg
niceritrol, but not in the group with 20 mg/kg. On the other hand, urinary
phosphate excretion was not significantly changed in the groups on 20-500 mg/kg.
Retention of phosphate was significantly suppressed in the groups on 100 and 500
mg/kg. A increased faecal phosphate excretion by niceritrol is presumably the
mechanism by which serum phosphate concentration is reduced in dialysis patients.
PMID- 10193808
TI - Validity of rapid estimation of glomerular filtration rate in type 2 diabetic
patients with normal renal function.
AB - BACKGROUND: Rapid estimation of the renal function is widely used in clinical
practice. METHODS: The validity of rapid estimation of renal function as well as
long-term changes in renal function from the Cockcroft-Gault formula for
estimation of creatinine clearance or from serum creatinine measurements was
evaluated against the 51Cr-EDTA plasma clearance technique in 36 type 2 diabetic
patients with normal renal function followed for 5.2 (2.7-7.5) (mean (range)
years. RESULTS: Compared with 51Cr-EDTA plasma clearance the Cockcroft-Gault
formula significantly underestimated glomerular filtration rate by 21%. The
degree of underestimation was observed over the whole range of glomerular
filtration rate studied and increased with increasing levels of isotopically
measured glomerular filtration rates. Serum creatinine was not significantly
associated with glomerular filtration rate. The average long-term change in renal
function was significantly overestimated by the Cockcroft-Gault formula (-2.8+/
2.3 ml/min/year) compared with the measured rate (-1.5+/-2.5 ml/min/year)
(P=0.002). The difference in change rate between the two methods was highest when
the measured fall rates were small and tended to disappear in patients with
faster fall rates. Changes in serum creatinine correlated significantly, but
imprecisely, with the rate of decline of measured glomerular filtration rate (r=
0.48, P=0.003). The variability of the estimated fall rate of renal function was
unacceptably high for all approaches. CONCLUSION: Valid estimates of glomerular
filtration rate as well as the rate of change in glomerular filtration rate
cannot be obtained by estimation of creatinine clearance from the Cockcroft-Gault
formula or from serum creatinine concentration measurements in type 2 diabetic
patients with normal renal function.
PMID- 10193809
TI - Urine N-acetyl-beta-D-glucosaminidase--a marker of tubular damage?
AB - BACKGROUND: Although an indicator of renal tubular dysfunction, an increased
urinary N-acetyl-beta-D-glucosaminidase (NAG) activity might reflect increased
lysosomal activity in renal tubular cells. METHODS: Puromycin aminonucleoside
(PAN) was administered to Sprague Dawley rats to induce proteinuria. Total
protein, albumin, NAG activity and protein electrophoretic pattern were assessed
in daily urine samples for 33 days. The morphological appearance of the kidneys
was examined on days three, four, six, eight and thirty three and the NAG
isoenzyme patterns on days zero, four, eight and thirty three. RESULTS: Following
intravenous PAN urine volume and urine NAG activity increased significantly by
day two, but returned to normal by day four. After day four all treated animals
exhibited a marked rise in urine albumin, total protein excretion and NAG
activity. Electrophoresis showed a generalised increase in middle and high
molecular weight urine proteins from day four onwards. Protein droplets first
appeared prominent in tubular cells on day four. Peak urine NAG activity and a
change in NAG isoenzyme pattern coincided with both the peak proteinuria and the
reduction in intracellular protein and NAG droplets (day six onwards).
CONCLUSIONS: This animal model demonstrates that an increase in lysosomal
turnover and hence urine NAG activity, occurs when increased protein is presented
to the tubular cells. Urine NAG activity is thus a measure of altered function in
the renal tubules and not simply an indicator of damage.
PMID- 10193810
TI - Autosomal recessive Alport syndrome: linkage analysis and clinical features in
two families.
AB - BACKGROUND: Genetic heterogeneity is a well-known feature of Alport syndrome
(AS). Most families with AS show an X-linked dominant pattern of inheritance but
about 15% of families show an autosomal inheritance of the disease. Autosomal
recessive AS may account for 10% of the total number of cases and is caused by
mutations in the COL4A3 and COL4A4 genes. The clinical spectrum of this rare
disorder has not been well clarified. METHODS: We present two families with AS.
Two affected members of these families have entered end-stage renal disease
(ESRD) in their 30s, and the other three are older than 15 years and have normal
serum creatinine. Four of the five patients have deafness but none have ocular
abnormalities. Two have been transplanted and have not suffered from anti-GBM
antibody nephritis. Men and women are equally affected. We have performed linkage
analysis for chromosome 2 with the following markers: D2S279, COL4A3/4 DNTR,
COL4A4 RFLP Hae III. RESULTS: We demonstrate that both families, one of them
consanguineous, are linked to the COL4A3/4 locus. CONCLUSIONS: We can conclude
that the only significant difference between the X-linked and the autosomal
recessive forms of AS lies in the fact that in the latter females are as affected
as males; thus the idea that autosomal recessive AS causes ESRD during childhood
must be discarded. Other clinical features such as age of deafness or the
presence of post-transplant anti-GBM antibody nephritis show no differences
between the entities. Thus an accurate familial study is mandatory in patients
with AS, as the identification of the different patterns of inheritance may cause
a great difference in genetic counselling. Linkage analysis is the only effective
molecular diagnosis that can be performed nowadays.
PMID- 10193811
TI - Long-term follow-up of a family with autosomal dominant polycystic kidney disease
type 3.
AB - BACKGROUND: Autosomal dominant polycystic kidney disease is one of the most
common hereditary diseases in man with an estimated prevalence of 1:1000. At
least three genetic loci are responsible for the development of the disease. PKD1
localized to 16p13 is the most common gene, contributing to almost 85% of all
cases, is associated with the most severe form. PKD2, localized to 4q21-23,
responsible for almost all the remaining cases, is associated with a milder form.
Up to now, only five families have been reported unlinked to the two most common
genetic defects, and therefore little is known about the clinical findings of the
non-PKD1/PKD2 families. METHODS: In this report we describe the clinical findings
of 18 patients of a non-PKD1/PKD2 family, with a mean follow-up of 52 months
(range 3-133 months) in our outpatient clinic. RESULTS: Of the 10 patients older
than 40 years, nine were hypertensive; in this age group eight patients exhibited
renal failure (two of them were on dialysis) and six had hepatic cysts. In eight
patients younger than 40 years, the only clinical finding was hypertension in
two. Considerable variation in the rate of progression to renal failure among
members of this family was found; on the other hand, some patients did not
exhibit any signs of progression. CONCLUSION: This family exhibits a more
aggressive phenotype, in contrast with the majority of the described non-PKD1/non
PKD2 families.
PMID- 10193812
TI - Does circulating erythropoietin reflect progression of IgA nephropathy?
Comparison with urinary N-acetyl-beta-D-glucosaminidase.
AB - BACKGROUND: Recent reports describe that erythropoietin (Epo) is produced by
peritubular interstitial fibroblast-like cells in response to a hypoxic stimulus.
We studied serum Epo levels as a possible marker of tubulointerstitial damage in
the progression of IgA nephropathy (IgAN), in comparison with urinary (u-) levels
of N-acetyl-beta-D-glucosaminidase (NAG), which is mainly derived from proximal
tubular cells and is used as a marker of tubular damage. METHODS: Thirty-eight
patients with IgA nephropathy (IgAN) with relatively preserved renal function
(serum creatinine: sCr, 0.5-2.2 mg/dl) were examined. The severity of
glomerulosclerosis and interstitial fibrosis of the renal biopsy tissue was
expressed by semiquantitative grading scores. Clinical parameters including serum
creatinine (sCr), blood pressures, and 24-h proteinuria levels were obtained at
the renal biopsy. Epo was measured by a radioimmunoassay (RIA) of sera obtained
in the morning and u-NAG was measured by colorimetric method of 24-h urine
samples. RESULTS: The mean Epo level of the patients (17.7+/-6.3 mU/ml) was not
different from the control level (19.3+/-3.7 mU/ml). There were no significant
correlations between Epo levels and red blood cell (RBC) counts, haematocrit
(Hct), or haemoglobin (Hb) levels. The mean u-NAG level of the patients (6.7+/
6.2 U/gCr) was significantly higher than the control level (1.9+/-0.5 U/gCr).
There was an inverse quantitative correlation between Epo and u-NAG levels in the
patients (P<0.02). The u-NAG levels showed quantitative positive correlations
with sCr (P<0.001), u-proteins (P<0.001), systolic (SBP) (P<0.001), and diastolic
blood pressures (DBP) (P<0.05). Conversely, Epo levels were inversely correlated
with sCr, SBP and DBP (each P<0.05). The patients with higher u-proteins (>2.0
g/day) showed significantly decreased Epo levels (P<0.05) than those with lower u
proteins (<2.0 g/day). The both scores of glomerulosclerosis and interstitial
fibrosis were positively correlated with the u-NAG levels (each P<0.001), but
were not correlated with the Epo levels. CONCLUSIONS: The significant correlation
between u-NAG and serum Epo levels suggests that tubular damage and interstitial
cell dysfunction are associated each other in the progression of IgAN. Serum Epo
levels bearing inverse correlations with sCr, blood pressure levels and heavy
proteinuria seem to reflect clinical severity of IgAN, whereas u-NAG can be more
useful progression marker of IgAN bearing correlations with both clinical and
histological findings.
PMID- 10193813
TI - The systemic and renal response to NO inhibition is not modified by angiotensin
II-receptor blockade in healthy humans.
AB - BACKGROUND: The role of angiotensin II (Ang II) in the systemic and renal
responses to acute nitric oxide (NO) synthesis inhibition has not been studied in
detail in healthy humans. The purpose of the present study was to investigate the
effects of Ang II receptor blockade on the systemic and renal response to acute
treat ment with Ng-monomethyl-L-arginine (L-NMMA) in healthy subjects. METHODS:
Mean arterial blood pressure (MAP), renal plasma flow (RPF), glomerular
filtration rate (GFR), sodium excretion (UNa*V), and plasma levels of renin, Ang
II, ANP, BNP, and cGMP were assessed in 15 healthy sodium replete humans before
and after acute L-NMMA treatment (3 mg/kg) on two occasions, i.e. after
pretreatment with the Ang II type 1 receptor (AT-1) antagonist candesartan
cilexetil (CAND; 8 mg) or placebo in a double blind, randomized fashion. Renal
haemodynamics were measured during water diuresis using renal clearances of
[125I]hippuran and [51Cr]EDTA. Plasma hormones were measured by
radioimmunoassays. RESULTS: On both study days L-NMMA treatment induced a
significant increase in MAP and a significant decrease in GFR, RPF, and UNa*V.
These effects of L-NMMA were not affected significantly by pretreatment with
CAND. The effects of L-NMMA on hormones were roughly similar on both occasions
with a drop in P-cGMP and U-cGMP. However, a fall in renin was observed only
during CAND pretreatment. CONCLUSIONS: We conclude that Ang II is not a major
mediator of acute vasoconstriction and sodium retention during acute lowering of
NO activity in healthy man.
PMID- 10193814
TI - Cardiovascular morbidity and risk factors in renal transplant patients.
AB - BACKGROUND: Cardiovascular disease is now the major cause of death in renal
transplant patients. This study aimed to assess the prevalence of cardiovascular
disease in stable renal transplant patients as compared with the general
background population, and to assess risk factors for cardiovascular disease in
this patient group. METHODS: A cross-sectional multicentre study comprising 406
stable renal transplant patients (age 47+/-16 years, 60% males, 71% taking
cyclosporin A) were assessed clinically and biochemically 48 months (median)
after transplantation and compared with the general population. Multivariate
analysis was used to assess the relation between cardiovascular disease and risk
factors. RESULTS: Hypertension was present in 55% of males and 34% of females
(P<0.001), in 51% with cyclosporin A and in 33% without (P<0.001). Ischaemic
heart disease (i.e. angina pectoris and/or previous myocardial infarction) was
present in 14% (males: 18%, females: 10%, P<0.05) and in 24% of diabetics vs 12%
of non-diabetics (P<0.01). Cerebro- and peripheral vascular disease was found in
3% and 4%, respectively. Odds ratio for angina pectoris (patients vs general
population) was: in age group 40-49 years (males/females), 12/16; 50-59 years,
6/4; 60-69 years, 3/4. Ischaemic heart disease was, besides age and gender,
independently associated with total cholesterol (P<0.01), and peripheral vascular
disease to systolic blood pressure (P<0.01). CONCLUSIONS: Cardiovascular disease
is highly prevalent in renal transplant patients, and is independently associated
with age, gender, total cholesterol and systolic blood pressure.
PMID- 10193815
TI - Nutritional status in type 2 diabetic patients requiring haemodialysis.
AB - BACKGROUND: Type 2 diabetic patients with end-stage renal disease are often
overweight (BMI > 24) at the start of dialysis therapy. However, there are very
few reports in the literature concerning the nutritional status of these patients
after prolonged haemodialysis treatment. Therefore, we compared nutritional
parameters in type 2 diabetic patients and age-matched non-diabetic patients
after at least 18 months of renal replacement therapy with haemodialysis.
METHODS: In a cross-sectional study, we measured BMI, serum albumin, total
protein, serum cholesterol and interdialytic weight gain (IWG), and performed a
subjective global assessment (SGA) in 14 patients with type 2 diabetes and 16 non
diabetic patients (aged > or = 50 years, haemodialysis therapy > or = 18 months).
Protein intake was estimated using the protein catabolic rate (PCR) and Kt/V was
calculated to compare the dose of dialysis. RESULTS: BMI was significantly higher
in patients with type 2 diabetes (30+/-7 vs 24+/-3, P<0.01). In contrast, the
concentration of serum albumin was significantly lower (3180+/-499 mg/dl vs
3576+/-431 mg/dl, P<0.05), but six of the diabetic patients had signs of chronic
inflammation. All other nutritional parameters did not differ between the two
groups. In addition, there were no significant differences in the intake of
protein (PCR 0.93+/-0.19 vs 0.92+/-0.22) and the dose of dialysis (Kt/V 1.13+/
0.19 vs 1.2+/-0.2). CONCLUSION: After > or = 18 months of haemodialysis therapy,
the majority of type 2 diabetic patients (9/14) were still overweight (BMI > 24).
The nutritional status of diabetic patients was similar to that of age-matched
non-diabetic patients on prolonged haemodialysis, but serum albumin levels were
significantly lower in diabetics. The lower albumin levels in the diabetic
patients may be explained by a state of subclinical chronic inflammation.
PMID- 10193816
TI - Hypochromic red cells and reticulocyte haemglobin content as markers of iron
deficient erythropoiesis in patients undergoing chronic haemodialysis.
AB - BACKGROUND: In patients on chronic haemodialysis, because of a non-specific
increase in serum ferritin, iron deficiency may be overlooked leading to failure
of erythropoietin treatment. A reticulocyte haemglobin content < 26 pg and a
percentage of hypochromic red cells > 2.5 have been proposed as markers of iron
deficient erythropoiesis in such subjects, but it is unclear which parameter is
superior. METHODS: We measured haematocrit, reticulocyte haemglobin content,
ferritin and the percentage of hypochromic red cells over 10-150 days in 36
chronic haemodialysis patients in a university hospital. Transferrin saturation
was also measured in a subset of 25 patients; iron deficiency was defined as a
transferrin saturation < 15%. RESULTS: The diagnostic sensitivity and specificity
of a reticulocyte haemoglobin content < 26 pg in detecting iron deficiency were
100% and 73% respectively, compared with 91% and 54% for a percentage of
hypochromic red cells > 2.5. Paradoxical reticulocyte haemglobin concentrations
occurred on follow-up in five patients receiving 4000 U erythropoietin per
haemodialysis (HD). In three patients, reticulocyte haemglobin content exceeded
26 pg despite a persistent lack of iron. In a fourth, iron gluconate (62.5 mg
i.v./HD) increased transferrin saturation to 27% and reduced the percentage of
hypochromic red cells from 12 to 4, while reticulocyte haemglobin remained > 30
pg. In the final patient, iron gluconate increased transferrin saturation from 8
to 30% and reduced the percentage of hypochromic red cells from 40 to below 5,
but reticulocyte haemglobin content remained < or = 26 pg throughout.
CONCLUSIONS: The reticulocyte haemglobin content is superior to the percentage of
hypochromic red cells in detecting iron deficiency in haemodialysis patients.
PMID- 10193817
TI - Quality of water used for haemodialysis: bacteriological and chemical parameters.
AB - BACKGROUND: The bacterial and chemical contamination of dialysate fluids are
important problems in haemodialysis therapy and may be caused by the water used
for dialysate preparation. METHODS: We performed a survey of the microbiological
and chemical quality of the water used in seven dialysis wards. Special attention
was paid to the effects of each water treatment step, for example ion exchange,
reverse osmosis and UV disinfection, on the number of bacteria (measured as
colony forming units, CFU), the amount of endotoxin (endotoxin units, EU) and
various chemical parameters, the main focus being on calcium, magnesium,
sulphate, aluminium and heavy metals. RESULTS: CFU values exceeding the European
Pharmacopeia value, determined at an incubation temperature of 22 degrees C, were
found in the samples of raw water (20.0%, n=25), after ion exchange (66.7%,
n=12), after reverse osmosis (33.3%, n=18) and also in samples of the dialysis
water taken at the inlets (12.5%, n=40) and outlets (50.0%, n=18) of the
machines. Whereas all raw water samples from the wards showed high mean values
for endotoxin (0.56-9.10 EU/ml) and the endotoxin levels were often enhanced
after ion exchange (0.13- >9.49 EU/ml), treatment by reverse osmosis led to a
satisfactory decrease in endotoxin in all samples (<0.03 EU/ml). Sufficient
reductions in calcium, magnesium and sulphate could only be achieved by the
combined application of ion exchange and reverse osmosis. Mercury contamination
was observed in the samples after ion exchange at three treatment plants, this
was possibly caused by polluted regenerants. Increased amounts of aluminium,
copper and zinc were found in water samples from different sites in the treatment
systems and were caused by materials in contact with the water. CONCLUSIONS: A
sufficient chemical water purification treatment system should consist of ion
exchange and reverse osmosis. Attention has to be paid to the suitability of
materials in contact with the water and of the chemicals used, for example
regenerants or corrosion inhibitors. From the microbiological point of view, a
safety UV disinfection step in the water-treatment system is favourable. To avoid
bacterial recontamination periodic cleaning and disinfecting of the water
treatment and distribution systems, as well as the dialysis machine are
essential. There is the need for complete guidelines regarding dialysis water
that include all relevant chemical and microbiological parameters. Based on this
standard, periodic examination of the water after each treatment step has to be
performed.
PMID- 10193818
TI - Influence of dialysis with polyamide vs haemophan haemodialysers on monokines and
complement activation during a 4-month long-term study.
AB - BACKGROUND: Contact between blood and dialysis membranes activates mononuclear
cells and the complement system. The extent of activation is dependent on the
dialyser material used and is considered an index of biocompatibility. Polyamide
dialysers consist of a synthetic membrane that claims high standards of
biocompatibility. Haemophan dialysers represent membranes made of modified
cellulose that are now broadly used for treatment in Europe and are already
considered to be more biocompatible than the cuprophane membranes that were used
as reference in most previous studies. METHODS: In a cross-over treatment study
short-term as well as long-term effects of a polyamide dialyser with respect to
monokine induction and complement activation were compared to a haemophan
dialyser. RESULTS: Neither haemophan nor polyamide dialysers induced relevant
changes in plasma monokine levels. However, in vitro challenge of mononuclear
cells with lipopolysaccharide (LPS) unmasked a significantly stronger
preactivation for the secretion of proinflammatory monokines during haemophan
than polyamide dialysis. Unlike other monokines the production of the regulatory
monokine IL-10 was mainly influenced by individual factors and correlated with
the patient's immune status rather than the dialyser type used. Enhanced
preactivation of monocytes in haemophan compared to polyamide dialysis was
paralleled by an increased complement activation. Cellular preactivation and
formation of terminal complement complex remained constant over the 4-month
treatment period. CONCLUSIONS: Haemophan and polyamide dialysers do not induce
changes in plasma cytokine levels both during short-term and long-term use.
However, they significantly differ in complement activation as well as
preactivation of monocytes. Preactivated monocytes are prone to secrete high
amounts of proinflammatory cytokines when exposed to a second stimulus like
endotoxin. Secretion of the regulatory cytokine IL-10 is not influenced by the
dialyser type.
PMID- 10193819
TI - Monitoring dialysis efficacy by comparing delivered and predicted Kt/V.
AB - INTRODUCTION: In Europe, especially in Germany, little is currently known about
the relationship between delivered and predicted haemodialysis doses for patients
on maintenance haemodialysis. We compared delivered and predicted Kt/V in
patients of an outpatient dialysis centre in Berlin by calculating the ratio of
delivered and predicted Kt/V, resulting in the efficacy quotient, QE. Moreover,
we studied the influence of technical and anthropometric parameters on both
delivered Kt/V and QE under routine clinical conditions. METHODS: Blood samples
were taken after the long interval in a thrice-weekly regimen before and 10 min
after ultrafiltration and 100 ml/min slow-pump method. Delivered Kt/V was
computed using the Daugirdas III formula. Predicted Kt/V was estimated from the
dialysis filter urea clearance given by the manufacturer, treatment time and the
total body water (V) computed by the Watson formula and was corrected for real
blood flow. As and when appropriate, bivariate and multivariate regression
analyses were used to make comparisons. RESULTS: The mean quotient (QE) between
delivered and predicted Kt/V was 1.02+/-0.20. Mean delivered Kt/V in 377
treatments of 128 patients was 1.28+/-0.27. Delivered Kt/V and QE were positively
associated (P<0.001). QE was significantly associated with post-HD urea, body
mass index (BMI) and sex, but not with session time. Significant positive
predictors for delivered Kt/V were post-dialysis urea, sex, session time, blood
flow and kind of vascular access. BMI was inversely related to delivered Kt/V.
DISCUSSION: In this study, the relationship between delivered and predicted Kt/V
(QE) was reproducible and close to the ideal value of 1.0. In contrast to
delivered Kt/V, QE was not influenced by session time, and positively by BMI.
Since QE gives a valid measure of technical dialysis efficacy we suggest the use
of this parameter in addition to delivered Kt/V to monitor HD adequacy in
clinical routine more comprehensively.
PMID- 10193820
TI - Percutaneous fibrin sleeve stripping of failing haemodialysis catheters.
AB - BACKGROUND: One of the most frequent reasons for failure of haemodialysis lines
is catheter blockage caused by fibrin sheath formation. We report our experience
of percutaneous fibrin sheath stripping in treating this problem. METHODS: A
consecutive series of failing haemodialysis catheters underwent percutaneous
fibrin sheath stripping in an attempt to retrieve and prolong the life of the
catheter. Immediate technical success, clinical success, and primary and
secondary patency were measured based on clinical follow-up. RESULTS: Sixteen non
functional permanent haemodialysis lines in 15 patients underwent percutaneous
fibrin sheath stripping on 21 occasions. Technical success rate was 100%.
Catheter flow rates sufficient for initial dialysis were achieved in 12 (75%)
lines. Successful percutaneous fibrin sheath stripping produced a mean catheter
patency of 126 days (range 6-299 days). CONCLUSIONS: Percutaneous fibrin sheath
stripping is a simple, repeatable procedure that can usefully extend the life of
a failing dialysis line. However, a randomized trial will be needed to evaluate
its role compared with catheter replacement.
PMID- 10193821
TI - Dialock: a new vascular access device for extracorporeal renal replacement
therapy. Preliminary clinical results.
AB - BACKGROUND: Vascular access, a vital tool for end-stage renal disease patients,
remains a weak component of extracorporeal renal replacement therapy (RRT) and
the first cause of morbidity. Permanent catheters proposed as an alternative to
permanent AV fistulae are associated with a significant risk of infection. A
subcutaneously implantable chamber connected to permanent catheter appears highly
desirable to reduce such hazards. METHODS: Dialock, a metallic port-like valve
device connected to permanent silicone twin catheters has been developed (Biolink
Corp, Middleboro, MA, USA). After being implanted subcutaneously below the
clavicle, Dialock provides a linear flow passage to two Silastic catheters placed
in the right atrium via the right internal jugular vein. The valve is accessed
percutaneously each dialysis session with needle cannulae that functionally
convert the device into twin catheters. Interdialytic patency of the catheters is
ensured by antithrombotic lock (heparin or low-molecular-weight heparin).
RESULTS: Dialock was implanted in 10 ESRD patients (64+/-12 years) under general
anaesthesia, with almost immediate use for HD. RRT consisted of three HD sessions
per week lasting 4 h; 699 HD sessions were performed. Average duration of use was
5.7 patient-months (1.3-9.6 months). Patient satisfaction was evident in all
cases. Three episodes of bacteraemia occurring in the early phase of the study
were cured by appropriate antibiotics. No device was removed because of
infection. Skin condition at the puncture sites has remained satisfactory in all
patients. Nurse training for cannulating was brief (2-3 x). Effective blood flow
was 307+/-3.3 ml/min, with a venous pressure of 195+/-39 mmHg and a recirculation
rate of 6.7+/-0.8%. Effective Kt/V dp delivered was 1.36+/-0.03 with a nPCR of
1.20+/-0.005 g/kg/day. Haematoma and a small amount of bleeding of the skin
puncture sites observed in the initial period of the study were effectively
prevented by reducing heparin lock volume. CONCLUSIONS: The Dialock device offers
a new and interesting vascular access alternative for haemodialysis bridging the
'gap' between permanent catheters and arteriovenous fistulae. Dialock's place in
the vascular access strategy for haemodialysis patients deserves further long
term clinical studies.
PMID- 10193822
TI - Pharmacokinetics of clodronate in haemodialysis patients.
AB - BACKGROUND: Clodronate is a bisphosphonate used in the treatment of
hypercalcaemia of various aetiologies. The major route of elimination of
clodronate is renal excretion. The aim of the study was to derive data for the
adjustment of dosage in haemodialysis patients. METHODS: The pharmacokinetic
parameters describing the fate of an intravenous infusion of 300 mg clodronate
disodium were studied in 10 haemodialysis patients. Clodronate disodium in serum,
urine and dialysate samples was analysed by capillary gas chromatography with
mass-selective detection. RESULTS: Of the 300 mg clodronate infused, 159 mg (53%)
was excreted into dialysate within 4 h. Clearance by haemodialysis (CLD) was
87.8+/-16.2 ml/min, accounting for 84% of total serum clearance (CLtot). Non
renal, non-dialysis clearance (CL(NRD)) represents the removal of the drug via
other routes than dialysis or kidneys. The greatest CL(NRD) was observed in
patients with most severe hyperparathyroidism. There was a positive correlation
between CL(NRD) and plasma intact PTH concentration. CONCLUSIONS: According to
the present findings, standard haemodialysis removes clodronate effectively from
the circulation, and total clearance in haemodialysis patients on a dialysis day
is not very different from that in healthy subjects. The regimen of dosing
intravenous clodronate in hypercalcaemia can also be used in haemodialysis
patients. The portion of clodronate eliminated by routes other than via dialysate
or kidneys, i.e. predominantly via skeletal deposition, was related to the
severity of hyperparathyroidism.
PMID- 10193823
TI - Mycophenolic acid plasma concentrations in kidney allograft recipients with or
without cyclosporin: a cross-sectional study.
AB - BACKGROUND: Combining cyclosporin (CsA) and prednisone with mycophenolate mofetil
(MMF) results in a significant reduction in the rate of biopsy-proven acute
rejection after kidney transplantation. This is achieved with a standard daily
MMF dosage of 2 or 3 g. Whether monitoring of the pharmacologically active
metabolite mycophenolic acid (MPA) will lead to improved safety and efficacy is
unclear. METHODS: We monitored MPA trough levels in 18 kidney transplant
recipients treated with CsA, prednisone, and MMF (63 samples) and in 11 patients
(31 samples) treated with prednisone and MMF only, in a cross-sectional study.
All patients were at least 3 months after transplantation with stable graft
function. All patients were treated with 2 g MMF for at least 3 months and 10 mg
prednisone. RESULTS: The MPA trough levels in the CsA-treated patients were
significantly lower (P<0.0001; Mann-Whitney) than those in patients on MMF and
prednisone only (mean MPA levels 1.98+/-0.12 vs 4.38+/-0.40 mg/l respectively).
CONCLUSIONS: Although all patients were treated with an identical MMF dose, a
significant difference was found in the MPA trough levels between CsA- vs non-CsA
treated patients. This suggests that CsA influences the MPA trough level. The
level at which CsA affects the MPA trough levels is unclear.
PMID- 10193824
TI - Effect of dialyser biocompatibility on recovery from acute renal failure after
cadaver renal transplantation.
AB - BACKGROUND: It has been reported that patients with acute renal failure (ARF)
requiring haemodialysis show an improved recovery of renal function when the
dialysis treatment is performed using a biocompatible membrane rather than a
bioincompatible membrane. However, most recent published human trials have not
been able to confirm these findings. METHOD: Over a 2-year period, we
prospectively studied 53 patients with ARF after cadaver renal transplantation
who required haemodialysis and randomized them into two treatment groups. One
group underwent dialysis with a cuprophane membrane and the other group underwent
haemodialysis with a more biocompatible membrane, polysulfone. All patients
received an immunosuppressive regimen which included azathioprine, prednisone and
cyclosporine. RESULTS: There was no difference by patient characteristics or
immunosuppressive regimen before acute tubular necrosis (ATN) recovery. In both
groups the number of haemodialysis sessions required prior to the recovery of
renal function (6.57+/-2.79 vs 6.05+/-2.40), the number of oliguric days (16.25+/
5.14 vs 14.40+/-4.67) and the number of hospital days (33.38+/-12.85 vs 30.10+/
11.00), were not statistically different. There was also no difference in long
term allograft outcome. CONCLUSION: Our data demonstrate that the use of a more
biocompatible membrane had no influence on the recovery from acute renal failure
after renal transplantation.
PMID- 10193825
TI - T lymphocyte subsets and cytokine production by graft-infiltrating cells in FSGS
recurrence post-transplantation.
AB - BACKGROUND: Focal segmental glomerulosclerosis (FSGS) aetiology remains undefined
although a derangement of lymphocytes and monocytes macrophages, at least, has
been strongly suspected. We report the graft-infiltrating phenotypes and their
cytokine production in a case of FSGS recurrence post-transplantation. METHODS:
The kidney transplant recipient suffered immediate FSGS recurrence. Aspiration
biopsies were done at the first and second week post-surgery and were analysed by
flow cytometry. The cytokine analysis was done on aspiration sample culture
supernatants and serum by enzyme-linked immunosorbent assay. RESULTS: High
expression of CD3CD69, CD3CD71 and CD4CD29 was found on infiltrating lymphocytes.
Biopsy cultures pointed to a Th0/Th1 pattern of cytokine production as well as
significant synthesis of transforming growth factor-beta1. Interestingly,
monocyte chemokines were absent. CONCLUSION: We report evidence of intragraft
lymphocyte activation in the early days of FSGS recurrence. Aspiration biopsy
cultures showed failure of cyclosporin A to inhibit interleukin-2 (IL-2)
production by infiltrating lymphocytes. If our findings are confirmed in similar
patients, a trial with anti-IL-2-receptor antibody could be warranted.
PMID- 10193826
TI - Lymphocyte subsets in renal allograft recipients with chronic hepatitis C virus
infection.
AB - BACKGROUND: The pathogenetic mechanisms of chronic hepatitis C virus (HCV)
infection in renal allograft recipients are not well established. This study
aimed to examine the relationship between altered immune status and HCV-related
liver disease, by determining the changes in peripheral blood lymphocyte and
natural killer (NK) cell subsets in these subjects. METHODS: Peripheral blood
lymphocyte, NK cell and activation markers were detected by flow cytometry in
renal allograft recipients with (TpC+) or without (TpC-) HCV infection, and
compared with age- and sex-matched patients with post-transfusional chronic HCV
infection (TfC+) and healthy controls. RESULTS: CD19+ cells were reduced in renal
allograft recipients compared with controls. TpC+ subjects had increased CD3+CD8+
cells compared with controls, and increased CD3+DR+ cells but reduced CD4+ CD38+
and CD3-CD16/56+ cells compared with controls as well as TfC+ patients. TfC+
patients and controls had similar numbers and proportions for the lymphocyte
subsets and NK cells. Chronic liver disease in HCV-infected renal allograft
recipients was associated with increased CD3+CD16/56+ cells but reduced CD4+CD38+
cells. Reduction of CD3-CD16/56+ cells was noted in TpC+ subjects without liver
disease. Yet among post-transfusional (TfC+) subjects this was associated with
chronic hepatitis. CONCLUSIONS: Peripheral blood suppressor/cytotoxic T
lymphocytes are increased, whereas activated helper/inducer T lymphocytes and NK
cells are reduced, in renal allograft recipients with HCV infection. Increased
non-MHC-restricted cytotoxic T cells and reduced NK cells are associated with the
presence or absence of liver disease respectively. These data suggest that immune
mechanisms are important in the pathogenesis of chronic hepatitis C after renal
transplantation.
PMID- 10193827
TI - Peritoneal clearance of leptin in CAPD patients: impact of local insulin
administration.
AB - INTRODUCTION: The ob gene product leptin is secreted by fat cells and the serum
leptin levels reflects the body fat content. Markedly elevated serum leptin
levels have been reported in patients with chronic renal failure. The aim of the
present study was to assess if the dialysate leptin levels in peritoneal
dialysate are similar to what can be expected from passive diffusion or if
intraperitoneal synthesis of leptin may occur. METHODS: We studied 39 patients
(20 males), mean age 54+/-12 years, who had been treated with peritoneal dialysis
for 17+/-12 months. Ten of the patients were diabetics of which seven used
intraperitoneal insulin. A 24-h collection of dialysate was performed and
dialysate and fasting blood samples were analysed for leptin, albumin and beta2
microglobulin, and the peritoneal clearances (PCl) were calculated for these
solutes. RESULTS: Serum leptin (mean 47+/-76, range 3-350 ng/ml) was related to
body mass index (r=0.35, P<0.05). In multiple regression analysis, serum leptin
also correlated to serum TNF-alpha. Although dialysate leptin levels correlated
to serum leptin, they were higher than expected from the molecular weight of 16
kD. PCl of leptin was 1.3 ml/min (range 0.2-5.9 ml/min), which was 1.6 times
higher than expected from the molecular weight of leptin and PCl for albumin and
beta2-microglobulin, not taking the protein binding of leptin into account. A
strong correlation was found between PCI for albumin and beta2-microglobulin (r =
0.68, P < 0.0001) but neither PCl albumin, nor PCl beta2-microglobulin correlated
to PCI leptin. The PCl of leptin was markedly higher in diabetics using
intraperitoneal insulin (n = 7) compared to the other 32 patients (2.6+/-2.0 vs
1.1+/-0.7 ml/min, P<0.05). CONCLUSION: Serum leptin is locally produced in the
peritoneal cavity, and intraperitoneal insulin enhances local production of
leptin.
PMID- 10193828
TI - Dialysis adequacy and homocyst(e)ine concentrations in peritoneal dialysis
patients.
AB - INTRODUCTION: Determinants of hyperhomocysteinaemia in peritoneal dialysis
patients have been recently reported but there is still conflicting data on the
influence of dialysis adequacy on homocysteine (Hcy). METHODS: We studied 46
consecutive new continuous ambulatory peritoneal dialysis (CAPD) patients to
determine the variation of Hcy before and 1 and 6 months after dialysis. The
variation in Hcy was analysed with respect to dialysis adequacy, factors known to
influence its metabolism, and Hcy peritoneal clearance. RESULTS: Hcy was 31.9+/-9
micromol/l before dialysis. It was significantly higher before dialysis than 1
month after the onset of PD (31.9+/-9 micromol/l vs 23.2+/-6.9 micromol/l, P <
0.0005). Weekly PD Hcy clearance was 14.3+/-5.4 1. There was no relationship
between pre-dialysis Hcy and 1 month post-dialysis Hcy (r=0.176, P=0.15). There
was a strong relationship between PD Hcy clearance and both PD creatinine
clearance (r=0.502, P<0.005) and Kt/V (r=0.42, P<0.005). There was no
relationship between Hcy and PD creatinine clearance (r= -0.221, P=0.11). In
contrast, the decrease in tHcy at 1 month was related to PD Hcy clearance
(r=0.487, P<0.01), to PD creatinine clearance (r= 0.349, P<0.02) and to Kt/V
(r=0.32, P<0.02). Multivariate analysis confirmed the relationship between the
decrease in Hcy and dialysis adequacy. Eleven patients (24%) experienced
arteriosclerotic complications. Fasting Hcy concentrations in this population
were significantly higher before and 1 month-post-dialysis than in patients
without cardiovascular complications. CONCLUSIONS: We observed a significant and
prolonged reduction in Hcy concentrations by peritoneal dialysis in end-stage
renal disease patients. The decrease in Hcy concentration was positively related
to dialysis adequacy. This study suggests the possibility that dialysis adequacy
may influence arteriosclerotic outcomes through an Hcy-lowering effect.
PMID- 10193829
TI - Leptin elimination in hyperleptinaemic peritoneal dialysis patients.
AB - BACKGROUND: Elevated plasma concentrations of leptin, a hormone thought to
regulate body composition by influencing food intake/metabolic rate, are
prevalent in renal failure patients. The mechanism for these increases is not
known, but evidence suggests that simple accumulation due to decreased
elimination is insufficient explanation. METHODS: We studied the incidence of
hyperleptinaemia in 28 end-stage renal disease patients treated with continuous
ambulatory peritoneal dialysis (CAPD), compared with body-mass-index-and sex
matched controls. Results were separated by gender because women have higher
leptin concentrations than men. Excretion of leptin and other substances in
dialysis fluid was also studied. RESULTS: Hyperleptinaemia was prevalent in women
CAPD subjects, but not in men. Plasma leptin concentrations correlated strongly
with the daily excretion of leptin in dialysis fluid. Clearance of leptin in
dialysis fluid was greater in men than women CAPD subjects. Single regression
analysis found that fasting insulin, glucose content of dialysis fluid, plasma
albumin, C-reactive protein, erythropoietin dose, urinary creatinine clearance
and plasma beta2-microglobulin were not determinants of plasma leptin
concentrations. Stepwise forward multiple regression, examining the dependence of
plasma leptin on body mass index, renal creatinine clearance, plasma albumin,
daily dialysis fluid glucose load, daily leptin in dialysis fluid, erythropoietin
dose and plasma C-reactive protein found only erythropoietin dose as a consistent
negative predictor of plasma leptin concentrations. CONCLUSIONS: The results
suggest that hyperleptinaemia of CAPD was due to predisposing loss of renal
elimination capacity combined with increased production due to obesity (more
prevalent in women subjects of this study) and potentially female gender.
PMID- 10193830
TI - Homocyst(e)ine and vascular access complications in haemodialysis patients:
insights into a complex metabolic relationship.
AB - BACKGROUND: As elevated total homocyst(e)ine (tHcy) is associated with increased
risk of vascular thrombosis, we hypothesized that the elevated levels of tHcy
seen in patients on haemodialysis may be associated with an increased risk of
thrombosis of native arteriovenous fistulae (vascular access failure). Our study
was designed to investigate the relationship between tHcy and vascular access
failure. The relationship between tHcy and mortality was explored as a secondary
analysis. METHODS: The study comprised a cross-sectional analysis of 96
haemodialysis patients at a single university-affiliated hospital and a
subsequent 9-month prospective follow-up of 88 of the 96 patients. RESULTS:
Levels of tHcy (median 30 micromol/l) were elevated. In the initial cross
sectional sample, there was an inverse relationship between tHcy and history of
vascular access failure which was not observed in the prospective study.
Variables influencing the risk of vascular access failure in the prospective
study included history of previous vascular access failure (RR=2.93, P=0.03), use
of antiplatelet agents (RR=0.13, P=0.01), increased urea reduction ratio (RR=0.55
for a 5% increase, P=0.01) and increased weight (RR=0.61 for a 10 kg increase,
P=0.02). Secondary analysis showed an unexpected inverse relationship between
tHcy and mortality (RR=0.033 for 1 log increase in tHcy, P=0.006), such that the
lower levels of tHcy were associated with an increased risk of death in short
term follow-up. CONCLUSION: We did not demonstrate a relationship between tHcy
and risk of vascular access failure. Patients with the lowest levels of tHcy
appeared to be at increased risk of death in this short-term follow-up. The
relationship of tHcy to vascular access complications and death in haemodialysis
patients appears complex and requires further study.
PMID- 10193831
TI - Protease inhibitor therapy for HIV infection: the effect on HIV-associated
nephrotic syndrome.
PMID- 10193832
TI - Dialysis without heparin in a patient with combined hereditary deficit in
coagulation factor V and protein C.
PMID- 10193833
TI - Acute renal cortical necrosis caused by an antifibrinolytic drug (tranexamic
acid).
PMID- 10193834
TI - Hepatic aneurysm and portal vein thrombosis in a patient with lupus erythematosus
on dialysis.
PMID- 10193835
TI - Engorgement of brachiocephalic vein after creation of an AV fistula--a result of
sternoclavicular joint osteophyte.
PMID- 10193836
TI - ACE inhibitor-induced transplant acute renal failure due to donor fibromuscular
dysplasia.
PMID- 10193837
TI - Vancomycin-dependent enterococci in a uraemic patient with sclerosing
peritonitis.
PMID- 10193838
TI - Sclerosing encapsulating peritonitis associated with recurrent eosinophilic
peritonitis.
PMID- 10193839
TI - Does intensive perioperative dialysis improve the results of coronary artery
bypass grafting in haemodialysed patients?
AB - BACKGROUND: Between January 1996 and April 1998, 17 chronic haemodialysed
patients underwent coronary artery bypass grafting (CABG). Two of them
simultaneously had valve replacement. METHODS: Except for two cases in which CABG
was performed in an emergency, 15 patients (CRF group) received 3 consecutive
days of haemodialysis in the preoperative period, intraoperative haemodialysis
connected to cardiac pulmonary bypass (CPB) and continuous hemodiafiltration in
the early postoperative period. The perioperative clinical parameters of the CRF
group were compared with those of 17 age-matched patients with normal renal
function undergoing CABG as the control (NRF group). RESULTS: When the
perioperative variables were compared, no significant differences were seen in
total operation time and CPB time, but we noted significant increases in the mean
volume of transfused blood in the 6 perioperative days, postoperative intubation
time, postoperative fasting time, and time spent in the intensive care unit.
Levels of central venous pressure, systolic blood pressure, respiratory index
(PaO2/FiO2) and daily fluid balance of the CRF group were the same as the control
group in the early postoperative period. In addition, the levels of serum
creatinine, urea nitrogen, potassium and hematocrit of CRF group remained almost
constant in the early postoperative period. After all, the hospital morbidity of
the CRF group was not more serious than that of the NRF group, and hospital
mortality of the CRF and NRF groups was 0%. CONCLUSIONS: Our intensive
perioperative dialysis programme could successfully manage the perioperative
clinical course of haemodialysed patients undergoing CABG.
PMID- 10193840
TI - The spectrum of acute renal failure in tumour lysis syndrome.
PMID- 10193841
TI - Recurrent renal failure associated with hypersensitivity to allopurinol.
PMID- 10193842
TI - Iatrogenic hypercalcaemia, hypokalaemia and metabolic alkalosis in a lady with
vena cava thrombosis--beware of overzealous diuretic treatment.
PMID- 10193843
TI - Familial mitochondrial tubulointerstitial nephropathy.
PMID- 10193844
TI - Second Symposium on Endothelin Antagonism, Zurich, Switzerland, March 5-7th,
1998.
PMID- 10193846
TI - Renal haemodynamic responses to a chicken or beef meal in normal individuals.
PMID- 10193845
TI - Spurious hepatitis B surface antigen detection in adult haemodialysis patients
following vaccination.
PMID- 10193847
TI - Henoch-Schonlein nephritis. Adverse effect of treatment with intravenous
immunoglobulin.
PMID- 10193848
TI - cANCA positivity in a case of IgA glomerulonephritis (IgAGN) with necrotizing
lesions.
PMID- 10193849
TI - Ecstasy-induced renal vasculitis.
PMID- 10193850
TI - Mycophenolate mofetil for primary biliary cirrhosis and sclerosis cholangitis?
PMID- 10193851
TI - Preliminary survey of the occurrence of anaphylactoid reactions during
haemodialysis.
PMID- 10193852
TI - From malaria to transplantation: the evolution of treatment for the nephrotic
syndrome in a single patient.
PMID- 10193853
TI - High incidence of left atrial thrombus in renal transplant recipients.
PMID- 10193854
TI - Multiple solid malignancies in a renal transplant patient.
PMID- 10193855
TI - Sociodemographic and nutritional determinants of obesity in Belgium.
AB - OBJECTIVE: To examine associations between sociodemographic, dietary factors and
physical activity and the prevalence of obesity in the Belgian general
population. DESIGN: Base-line data from the Belgian Interuniversity Research on
Nutrition and Health (BIRNH) study (1979-1984). SUBJECTS: A total of 5837 men and
5243 women aged 25-74y were included in the analysis. The sample was considered
representative of the Belgian population. MEASUREMENTS: Using the body mass index
(BMI) as the criterion, obesity was defined as a BMI> or =30 kg/m2. Nutritional
data were assessed by a 24 h food record. Physical activity level (PAL) was
calculated by dividing total caloric intake by an estimation of basal metabolic
rate (BMR, predicted from gender, weight and age). Age-adjusted odds ratios (OR)
of the prevalence of obesity were estimated by multilogistic regression analysis.
RESULTS: Prevalence of obesity was 12.1% in men and 18.4% in women. In both
sexes, prevalence of obesity increased gradually in each 10-year age category
(P<0.0001) and steeply decreased with level of education. Comparing lowest (Q1)
to highest quartile (Q4), after adjustment for age, prevalence of obesity
decreased with total carbohydrate intake, as well as total sugar intake in both
sexes, and increased with total fat intake only in men. Obesity increased with a
high fat to sugar ratio (men: OR(Q4/Q1) = 1.56; confidence interval (CI): 1.25
1.93; women: OR(Q4/Q1) = 1.45; CI: 1.17-1.80). PAL was inversely and very
strongly associated with obesity (men: OR(Q4/Q1) = 0.20; CI: 0.15-0.26; women:
OR(Q4/Q1) = 0.18; CI: 0.14-0.23). The same associations were observed with the
mean BMI. CONCLUSION: This study indicates that prevalence of obesity is
particularly high in Belgium. Low level of education and reduced physical
activity, increased fat intake and especially elevated fat to sugar ratio appear
to be powerful determinants of obesity in this Belgian population.
PMID- 10193856
TI - Catecholamine-induced lipolysis in obesity.
AB - Catecholamines are the only hormones with pronounced lipolytic action in man. A
number of in vivo and in vitro studies suggest that there is lipolytic resistance
to catecholamines in subcutaneous adipose tissue, which is the major fat depot in
obese subjects. This is due to multiple alterations in catecholamine signal
transduction, involving decreased expression and function of beta2-adrenoceptors,
increased function of alpha2-adrenoceptors and decreased ability of cyclic
monophosphate (AMP) to stimulate hormone sensitive lipase. A sedentary life
style, which usually characterizes obesity, may contribute to the catecholamine
resistance. However, hereditary/genetic factors may also be involved. Recently,
decreased expression and function of hormone sensitive lipase has been found in
subcutaneous adipocytes of non-obese subjects with heredity for obesity. In
addition, polymorphisms in the genes for beta2-adrenoceptors, beta3-adrenoceptors
and hormone sensitive lipase, associate with obesity. On the other hand,
catecholamine-induced lipolysis in visceral adipose tissue is increased in
obesity due to increased function of beta3-adrenoceptors (major finding),
decreased function of alpha2-adrenoceptors and increased ability of cyclic AMP to
stimulate lipolysis. When the findings in different adipose regions are
considered together, it appears that there is a redistribution of lipolysis and
thereby fatty acid mobilization in obesity, favouring the visceral fat depot.
This leads to an increase in the circulating fatty acid levels in the portal
vein, which connects visceral fat with the liver. As a consequence, the liver
function may be altered leading to hyperinsulinemia, hyperglycemia and
dyslipidemia, which usually accompany the obese state.
PMID- 10193857
TI - Determinants of postprandial lipemia in obese women.
AB - OBJECTIVE: To quantify the effects of fasting lipids, age, apolipoprotein (apo) E
polymorphism, insulin resistance, body fat and abdominal fat distribution, on
postprandial lipemia (PPL) in non-diabetic obese women. DESIGN: Cross-sectional,
prospective. SUBJECTS: A total of 93 obese women (mean +/- s.d. age 39+/-13y;
body mass index (BMI) 38.3+/-4.9 kg/m2) and 16 nonobese women (25+/-8y; BMI
22.7+/-3.2 kg/m2). MEASUREMENTS: Body fat distribution was determined by the
ratio of waist-to-hip circumferences (WHR) and by computed tomography (CT) at the
L4-L5 level. Apo E genotyping was performed by restriction isotyping. Insulin
resistance was calculated from fasting glucose and insulin concentrations. PPL
was evaluated using the vitamin A-fat tolerance test (1.0 g fat/kg body weight
and 7.0 mg cholesterol/kg body weight+300000 IU vitamin A palmitate). Blood
samples were drawn before, and every 1.5 h for 7.5 h plus 24 h after ingestion of
the fat meal. Areas under the response curves (AUC) for triglycerides (TG) and
retinyl palmitate (RP) were calculated using the geometrical method for two time
intervals, that is, 0-7.5 h and 0-24 h. RESULTS: Incremental AUCs TG, but not
AUCs RP, were increased in the obese women. Apo E polymorphism, BMI, WHR and
menopausal state did not influence PPL in the obese women. Fasting TG, age, the
intra-abdominal to subcutaneous abdominal fat ratio (IA/SC ratio) and insulin
resistance were independent determinants of PPL. Together, fasting TG, IA/SC
ratio and insulin resistance, explained 38% of the variance in AUC TG 0-7.5 h (P
= 0.0001). CONCLUSION: Alterations in PPL are to be added to the increasing
number of components of the plurimetabolic syndrome.
PMID- 10193858
TI - Leptin: fundamental aspects.
AB - The discovery of leptin, the product of the ob gene, has led to major
developments in understanding the regulation of energy balance. It is now
recognised that leptin is produced in several organs additional to white adipose
tissue, including brown fat, the placenta and fetal tissues (such as heart and
bone/cartilage). The hormone has multiple functions-in inhibiting food intake, in
the stimulation/maintenance of energy expenditure, as a signal to the
reproductive system and as a 'metabolic' hormone influencing a range of processes
(for example, insulin secretion, lipolysis, sugar transport). The production of
leptin by white fat is subject to a number of regulatory influences, including
insulin and glucocorticoids (which are stimulatory), and fasting and beta
adrenoceptor agonists (which are inhibitory). A key role in the regulation of
leptin production by white fat is envisaged for the sympathetic system, operating
through beta3-adrenoceptors. The leptin receptor gene is widely expressed, with
the several splice variants exhibiting different patterns of expression. The long
form variant (Ob-Rb) is expressed particularly in the hypothalamus, although it
is being increasingly identified in other tissues. Leptin exerts its central
effects through several neuroendocrine systems, including neuropeptide Y,
glucagon-like peptide-1, melanocortins, corticotrophin releasing hormone (CRH)
and cocaine- and amphetamine-regulated transcript (CART). In essence, the leptin
system now appears highly complex, the hormone being involved in a range of
physiological processes in a manner far transcending the initial lipostatic
concept. This complexity may reduce the potential of the leptin system as a
target for anti-obesity therapy.
PMID- 10193859
TI - Clinical endocrinology of human leptin.
AB - Since the discovery of leptin, a boom of scientific knowledge became available
about the OB-protein gene and its role and significance in weight regulation.
Both from animal and human research data, serum leptin can probably be considered
as one of the best biological markers to reflect total body fat, and this finding
is true over a wide range of body mass indexes (BMIs) and in different
pathologies: in normal weight, anorexic and obese subjects; in non insulin
dependent diabetes mellitus (NIDDM) patients, PCO women, Prader-Willi children
and subjects with hypogonadism and growth hormone deficiency. Gender differences
clearly exist, probably related to sex hormone differences, and from fat
distribution studies it could be shown that subcutaneous fat is much more related
to serum leptin concentrations than visceral fat: also leptin messenger-RNA (m
RNA) expression is significantly higher in subcutaneous fat from human obese
subjects. Leptin is not only correlated to a series of endocrine parameters such
as insulin, insulin-like growth factor, (IGF) and SHBG, it seems involved as a
mediator in some endocrine mechanisms (onset of puberty, insulin secretion, etc)
as well. Weight loss will reduce human leptin concentrations, whereas the
administration of human recombinant leptin seems to show only limited effects.
PMID- 10193860
TI - Metabolic predictors of weight gain.
AB - Human obesity is the result of both environmental and genetic factors. In this
manuscript, we briefly review the metabolic factors predicting body weight gain
in Pima Indians, a population prone to obesity. The metabolic predictors of
weight gain are: 1) a low metabolic rate, 2) low levels of physical activity, 3)
low rates of fat oxidation, 4) insulin sensitivity, 5) low sympathetic nervous
system activity, and 6) low plasma leptin concentrations. In contrast, obesity is
associated with high metabolic rate, high fat oxidation, low insulin sensitivity
and high plasma leptin concentration. This observation emphasizes the need to
conduct prospective studies to obtain a better understanding of the etiology of
obesity. In addition, genetic studies will help to identify new pathways involved
in the pathophysiology of obesity.
PMID- 10193861
TI - Obesity and hypertension: from pathophysiology to treatment.
AB - While the prevalence of hypertension is clearly increased among the overweight
persons, the pathophysiological mechanisms underlying this frequent association
of obesity and hypertension are still poorly understood. The expansion of
extracellular volume, inducing hypervolaemia and increased cardiac output,
represents the characteristic haemodynamic feature of the obesity-related
hypertension. The maintenance of hypervolemia in the face of elevated blood
pressure, indicates a resetting of pressor natriuresis toward higher blood
pressure. The development of hypertension also indicates an increase in
peripheral vascular resistance, thus the lack of physiological adaptation of
peripheral resistance to increased cardiac output. The mechanisms underlying
these changes in renal function and vascular reactivity can no longer be
attributed to hyperinsulinaemia as such, but might be related to insulin
resistance responsible for the enhancement in pressor activity of noradrenaline
and angiotensin II. This increased reactivity to pressor factors may be due to an
inadequate nitric oxide generation by vascular endothelium and to increased
sodium and calcium concentration in vascular smooth muscle cells. The role of
increased neuropeptide Y (NPY) activity, may also be involved. As to enhancement
of tubular sodium reabsorption, it could be related to histological changes
within the renal medulla, leading to compression of tubules and vasa recta, hence
a more efficient sodium reabsorption. As to the therapeutic approach, the low
energy sodium-restricted diet associated with increased physical activity,
represents the cornerstones of treatment for the obesity-related hypertension. If
this approach fails, the pharmacological treatment becomes necessary, and the use
of the converting enzyme inhibitors seems to be the most appropriate choice of
drug therapy for hypertensive obese patients.
PMID- 10193862
TI - Pharmacological treatment of obesity: present status.
AB - OBJECTIVE: Obesity poses a serious health hazard and its treatment is often
disappointing. This review describes the present status of pharmacological
treatment of obesity in man. DESIGN: Obesity treatment may include drugs that
reduce food intake, drugs that increase energy expenditure and drugs that affect
nutrient partitioning or metabolism. The mode of action, efficacy and safety of
each approach will be briefly discussed. RESULTS: All of the pharmacological
possibilities have potential activities, but also serious limitations. While
current anti-obesity pharmacotherapy essentially uses centrally-acting anorectic
drugs, severe side-effects (more particularly pulmonary hypertension and valvular
heart disease) have been reported, leading to the withdrawal of licensed
fenfluramine and d-fenfluramine. New approaches have been recently proposed, such
as sibutramine, an amine reuptake inhibitor which decreases food intake, and
orlistat, an intestinal lipase inhibitor which decreases fat absorption. Obesity
is a chronic disease and should be treated as such with reasonable expectations.
Large-scale one-year placebo-controlled studies demonstrated that d-fenfluramine,
sibutramine and orlistat significantly increased body weight loss by an average
of 2-4 kg when compared to placebo and, more interestingly, multiplied by 2-3 the
number of patients who succeeded in obtaining and maintaining a reduction of more
than 10% of initial body weight. Interestingly, some of these compounds may also
exert favourable effects on other vascular risk factors, independently of weight
loss. CONCLUSIONS: Even if all anti-obesity pharmacological approaches can be
helpful, they also have important limitations so that other strategies including
either combined therapies or new drugs (peptides) are currently under
investigation.
PMID- 10193863
TI - Melanocortin-4 receptor: a novel signalling pathway involved in body weight
regulation.
AB - For many years, genetically obese mouse strains have provided models for human
obesity. The Avy/-agouti mouse, one of the oldest obese mouse models, is
characterized by maturity-onset obesity and diabetes as a result of ectopic
expression of the secreted protein hormone, agouti protein. Agouti protein is
normally expressed in hair follicles to regulate pigmentation through antagonism
of the melanocortin-1 receptor, but in-vitro studies have demonstrated that the
hormone also has potent antagonist activity for the melanocortin-4 receptor (MC4
R). Subsequent development of the MC4-R knockout mouse model demonstrated that
MC4-R plays a role in weight homeostasis as these mice recapitulated the
metabolic defects of the agouti mouse. Further evidence for this hypothesis was
obtained from pharmacological studies utilizing peptides with MC4-R agonist
activity, that inhibited food intake (when administered intracerebrally).
Additional studies with peptide antagonists have now implicated the MC4-R in the
leptin signalling pathway. Finally, evidence that the MC4-R may play a role in
human obesity has been obtained from the identification of a dis-functional
variant of the receptor in genetically obese subjects.
PMID- 10193864
TI - Obesity and physical activity.
AB - OBJECTIVES: Three aspects of obesity and physical activity are reviewed: whether
the obese are inactive; how the activity level can be increased; and which are
the effects of an increase in physical activity in combination with a reduction
of energy intake. METHOD: The focus is on an objective approach that is, activity
associated energy expenditure as measured with doubly labelled water. RESULTS:
Activity associated energy expenditure increases with body mass index while the
average physical activity level does not change. The majority of obese subjects
is moderately active. An increase in the activity level of obese subjects is
limited by the ability to perform exercise of higher intensity. Training programs
obese subjects can cope with are until now not rewarded by weight loss. A
possible loss in fat mass is compensated by a gain in fat-free mass. CONCLUSIONS:
Obese subjects can only reach a significant weight loss with an energy restricted
diet. Mild energy restriction will already result in very significant weight loss
when one complies with the diet. An increase in physical activity is necessary to
compensate for the reduction in activity induced energy expenditure and should be
facilitated by the lower body mass.
PMID- 10193865
TI - A multidisciplinary approach to the treatment of obesity.
AB - OBJECTIVE: The aim of this paper is: (1) To describe a long-term
multidisciplinary group approach to the treatment of morbidly obese persons; and
(2) to present, in a preliminary report, results at three months in 30 obese
women. DESIGN: Prospective study with evaluation at the start of therapy and
after three months of therapy. SUBJECTS: Thirty obese women, initial mean BMI
35.3 kg/m2, age 28-67 y. RESULTS: Body weight decreased significantly (-6 kg)
with 74% of weight loss as fat mass. This moderate decrease in body weight
resulted in a significant improvement of VO2max/kg body weight. Resting metabolic
rate and metabolic parameters remained unchanged. Among psychological variables,
participating in the therapy resulted in a more pronounced restrained eating
behaviour, an improvement of body image and a higher expression of positive
feelings and actions. CONCLUSION: Preliminary results of the program are
encouraging. However, continuous evaluation and improvement of the program in the
long-term (at least several years) are extremely important.
PMID- 10193866
TI - Obesity stigmatization and coping: relation to mental health symptoms, body
image, and self-esteem.
AB - OBJECTIVE: To create inventories of stigmatizing situations faced by obese people
and ways of coping with stigmatization, and to examine how stigma and coping are
related to psychological distress in an obese patient population. DESIGN: Study
1: Items were generated by asking obese people to list stigmatizing situations
they had encountered and their ways of coping. Study 2: Obese patients were
surveyed about the frequency with which they encountered each form of
stigmatization and employed each form of coping. Cross-sectional data on current
psychological adjustment were obtained. SUBJECTS: Study 1: 63 obese patients
(body mass index, BMI > 40 kg/m2); 38 obese non-patients, seven professionals who
work with obese patients and 32 obese female authors from the print media. Study
2: 112 gastric bypass patients (BMI 33.9-80.9 kg/m2) and 34 less obese patients
(BMI 27.1-57.2 kg/m2). MEASUREMENT: Study 1: Collection of stigmatizing
situations and coping responses. Study 2: Frequency of stigmatizing experiences
and coping responses, psychological symptoms, body image, and self esteem
measures. RESULTS: Study 1 resulted in two objective questionnaires, consisting
of 50 situations and 99 responses. Study 2 found that stigmatization is a common
experience, and that obese subjects frequently engage in some effort to cope with
stigma. More frequent exposure to stigmatization was associated with greater
psychological distress, more attempts to cope, and more severe obesity. Certain
coping strategies are associated with greater distress.
PMID- 10193867
TI - Cognitive appraisals of dietary transgressions by obese women: associations with
self-reported eating behavior, depression, and actual weight loss.
AB - OBJECTIVE: To identify three groups of obese people entering weight loss
treatment, who have distinctly different cognitive appraisals of dietary
transgressions and to compare these groups on self-report inventories of eating
patterns, dieting, and depression, as well as on treatment completion rates and
weight loss. DESIGN: Retrospective review of clinical records. Using a measure
which evaluates eating-related cognitive appraisals, participants were
categorized into one of three cognitive groups (All-or-None, Rationalization,
Matter-of-Degree). SUBJECTS: 289 treatment-seeking obese women (age: 40.9 y, body
mass index (BMI): 34.7 kg/m2). MEASUREMENTS: Self-reported eating and dieting
behavior (Three-Factor Eating Questionnaire and Eating Behavior Inventory);
depression (Beck Depression Inventory); attendance information and body weight
obtained during treatment. RESULTS: The cognitive group representing objective
thinkers (Matter-of-Degree) reported significantly fewer problems with overeating
and more personal control over eating than did the rigid, dichotomous thinkers
(All-or-None). In addition, the Matter-of-Degree (MAT) group endorsed
significantly less subjective hunger and fewer depressive symptoms than the other
two cognitive groups. The Rationalization group was more likely to complete a
treatment program than was the All-or-None group, with the MAT group not
differing from either. Despite these findings, there were no significant
differences among cognitive groups on total weight loss. CONCLUSIONS: Cognitive
appraisals of weight-control lapses appear to be associated with self-reported
eating behavior, depressive symptoms and treatment completion rates, but not with
treatment-induced weight loss. The relationship between long-term weight loss and
cognitive appraisals of dieting lapses is yet to be determined. It appears
necessary to assess empirically the validity of assumptions regarding factors
associated with treatment outcome.
PMID- 10193868
TI - Benidipine induces thermogenesis in brown adipose tissue by releasing endogenous
noradrenaline: a possible mechanism for the anti-obesity effect of calcium
antagonists.
AB - BACKGROUND: Anti-obesity effects of calcium antagonists such as benidipine and
nifedipine have been described in rodent obesity models, but the mode of action
of the calcium antagonists as anti-obesity agents has not been established.
OBJECTIVE: To examine whether the anti-obesity effects of calcium antagonists
(here benidipine) could be ascribed to a direct stimulation of brown adipose
tissue (BAT) thermogenesis. METHODS: Examination of the ability of benidipine to
induce thermogenesis (increased rate of oxygen consumption) in isolated brown-fat
cells from rats, mice and hamsters--and in intact cold-acclimated rats. RESULTS:
Benidipine itself, or in combination with any dose of noradrenaline (NA), was
totally unable to induce or augment thermogenesis in isolated brown-fat cells of
any species tested. However, it markedly induced thermogenesis in intact animals
(approx 60% increase over resting metabolic rate). This effect could be fully
inhibited by propranolol. CONCLUSION: Benidipine is itself without thermogenic
effect. The thermogenic response in-vivo (and thus presumably the anti-obesity
effect) is probably secondary to a previously described general side-effect of
calcium antagonists: a release of NA from sympathetic nerves, here most likely
directly from nerves in the BAT. The anti-obesity effect of benedipine is thus
probably not due to its calcium channel blocking effect. PERSPECTIVES: It is
probable that the anti-obesity effects of calcium antagonists reported in several
models of genetically obese rodents (MSG-obese and agouti mice, SHHF/Mcc-fa(cp)
and JCR:LA-corpulent rats) are mediated via an indirect stimulation of BAT. To
what extent calcium antagonists may induce similar effects in a clinical
situation, is currently unknown.
PMID- 10193869
TI - A study in the relationships between leptin, insulin, and body fat in Asian
subjects.
AB - OBJECTIVE: To study the relationship of leptin concentrations with indices of
obesity, fasting insulin, insulin resistance and lipid profiles (total
cholesterol, low density lipoprotein (LDL)-cholesterol, high density lipoprotein
(HDL)- cholesterol and triglyceride) in an Asian cohort. DESIGN: Cross sectional
study. SUBJECTS: A total of 133 healthy volunteers were enrolled (64 female: age:
25-61 y, body mass index (BMI): 18.7-45.1 kg/m2 and 69 male: age: 25-61 y, BMI:
19.3-35.0 kg/m2). MEASUREMENTS: Weight, height, waist and hip circumferences,
blood pressure, lean body mass (by bioelectric impedence analysis (BIA)), plasma
leptin and lipid profiles were taken after a 10 h fast. RESULTS: Percentage of
body fat measured by bioelectric impedance was the strongest determinant of
plasma leptin (r = 0.844, P < 0.0001). Females had higher leptin concentrations
than males for the same fat mass. In a multiple linear regression model, body fat
percentage, (percentage body fat* gender), hip circumference and fasting insulin
were significant determinants of leptin concentration (r = 0.882, P < 0.0001).
CONCLUSION: Leptin concentration correlated closely with percentage body fat in
Asian subjects. Hip circumference as a corollary for peripheral obesity, was
better associated with leptin than waist circumference or waist-to-hip ratio
(WHR). Distribution of fat in females tended to be peripheral and may partly
explain the gender difference. Fasting insulin level and central obesity were
correlated with HDL-cholesterol, triglyceride and blood pressure, while fasting
leptin had little correlation with these metabolic parameters. Therefore, insulin
resistance was a better guide to cardiovascular risk assessment than plasma
leptin.
PMID- 10193870
TI - Predicting body composition from anthropometry in pre-adolescent children.
AB - The objectives of this paper were to: a) evaluate the accuracy and precision of
previously published pediatric body composition prediction equations and b)
develop additional prediction equations from a large, heterogeneous group of
Caucasian (n = 133) and African-American (n = 69) children. The combined cohort
of 202 children included a wide range of ages (4.0-10.9 y), weights (14.0-70.8
kg), fat mass (FM: 1.2-28.5 kg) and percent body fat (% body fat: 6.2-49.6%).
Skinfold measurements were obtained using a Lange caliper and body fat was
measured with a Lunar DPX-L densitometer. The previously published equations of
Slaughter et al and Goran et al did not accurately predict body fat. The entire
cohort was randomly divided into two sub-groups for purposes of deriving and
cross-validating a new prediction equation. In stepwise regression analysis in
the development group (n = 135), weight, triceps skinfold, gender, ethnicity and
abdominal skinfold estimated FM measured by dual energy x-ray absorptiometry
(DEXA) with a model R2 of 0.95. The new prediction equation was cross-validated
in the control group (n = 67) and each ethnic and gender subgroup. We conclude
that a) the equations of Slaughter et al and Goran et al did not accurately
predict FM in a heterogeneous group of children and b) a new anthropometric
prediction equation is proposed that may provide accurate estimates of FM in both
Caucasian and African-American children aged 4-10 y with a wide range of FM and
body composition.
PMID- 10193871
TI - Growth hormone in obesity.
AB - Growth hormone (GH) secretion, either spontaneous or evoked by provocative
stimuli, is markedly blunted in obesity. In fact obese patients display, compared
to normal weight subjects, a reduced half-life, frequency of secretory episodes
and daily production rate of the hormone. Furthermore, in these patients GH
secretion is impaired in response to all traditional pharmacological stimuli
acting at the hypothalamus (insulin-induced hypoglycaemia, arginine, galanin, L
dopa, clonidine, acute glucocorticoid administration) and to direct somatotrope
stimulation by exogenous growth hormone releasing hormone (GHRH). Compounds
thought to inhibit hypothalamic somatostatin (SRIH) release (pyridostigmine,
arginine, galanin, atenolol) consistently improve, though do not normalize, the
somatotropin response to GHRH in obesity. The synthetic growth hormone releasing
peptides (GHRPs) GHRP-6 and hexarelin elicit in obese patients GH responses
greater than those evoked by GHRH, but still lower than those observed in lean
subjects. The combined administration of GHRH and GHRP-6 represents the most
powerful GH releasing stimulus known in obesity, but once again it is less
effective in these patients than in lean subjects. As for the peripheral limb of
the GH-insulin-like growth factor I (IGF-I) axis, high free IGF-I, low IGF
binding proteins 1 (IGFBP-1) and 2 (IGFBP-2), normal or high IGFBP-3 and
increased GH binding protein (GHBP) circulating levels have been described in
obesity. Recent evidence suggests that leptin, the product of adipocyte specific
ob gene, exerts a stimulating effect on GH release in rodents; should the same
hold true in man, the coexistence of high leptin and low GH serum levels in human
obesity would fit in well with the concept of a leptin resistance in this
condition. Concerning the influence of metabolic and nutritional factors, an
impaired somatotropin response to hypoglycaemia and a failure of glucose load to
inhibit spontaneous and stimulated GH release are well documented in obese
patients; furthermore, drugs able to block lipolysis and thus to lower serum free
fatty acids (NEFA) significantly improve somatotropin secretion in obesity.
Caloric restriction and weight loss are followed by the restoration of a normal
spontaneous and stimulated GH release. On the whole, hypothalamic, pituitary and
peripheral factors appear to be involved in the GH hyposecretion of obesity. A
SRIH hypertone, a GHRH deficiency or a functional failure of the somatotrope have
been proposed as contributing factors. A lack of the putative endogenous ligand
for GHRP receptors is another challenging hypothesis. On the peripheral side, the
elevated plasma levels of NEFA and free IGF-I may play a major role. Whatever the
cause, the defect of GH secretion in obesity appears to be of secondary, probably
adaptive, nature since it is completely reversed by the normalization of body
weight. In spite of this, treatment with biosynthetic GH has been shown to
improve the body composition and the metabolic efficacy of lean body mass in
obese patients undergoing therapeutic severe caloric restriction. GH and
conceivably GHRPs might therefore have a place in the therapy of obesity.
PMID- 10193872
TI - School performance and weight status of children and young adolescents in a
transitional society in Thailand.
AB - OBJECTIVE: To study the association between current or previous weight status and
school performance among children and young adolescents of Hat Yai municipality,
southern Thailand. DESIGN: Cross-sectional and longitudinal study. SETTING:
Primary and secondary schools of Hat Yai municipality, southern Thailand.
SUBJECTS: 1207 grades 3-6 and 587 grades 7-9 students. MEASUREMENTS: Body mass
index (BMI, kg/m2) calculated from weight and height measurement of subjects in
1992 and 1994; parental education level and occupation, and monthly income, by
questionnaire performed in 1992; grade-point-average (GPA) and grades of
mathematics and Thai language from the school records of final examinations in
1994. RESULTS: Overweight subjects (BMI value > 85th percentile of the NHANES-I
data for age and gender) in grades 7-9 had a mean GPA 0.20 point (95% confidence
internal (CI) = 0.04, 0.37) lower than that of the normal weight children after
controlling for gender, age, school and grade. They were twice more likely to
have low grades (lower than 2 on the scales of 0-4) of mathematics and Thai
language than normal weight children. There were no associations between GPA or
individual subject grades and previous BMI status in 1992. Children in grades 7-9
who became overweight over the two years, had a mean GPA of 0.48 point lower than
those who did not become overweight (95% CI = 0.12, 0.84). In grades 3-6
subjects, however, becoming overweight had no effect on GPA and individual
subject scores. CONCLUSIONS: Our study showed that being overweight and becoming
overweight during adolescence (grades 7-9) was associated with poor school
performance, whereas such an association did not exist in children (grades 3-6).
PMID- 10193873
TI - Linkages and associations between the leptin receptor (LEPR) gene and human body
composition in the Quebec Family Study.
AB - OBJECTIVE: To investigate linkage and association between the leptin receptor
(LEPR) gene and body composition variables in the Quebec Family Study (QFS).
DESIGN: Single-point linkage analysis using families, and covariance and chi
square analyses using normal weight and obese unrelated subjects from QFS.
SUBJECTS: 169 nuclear families were used for linkage study. 308 unrelated
subjects (146 males; 162 females) from these families were used for chi-square
testing of genotype and allele distributions between subjects with body mass
index (BMI) < 27 kg/m2 (n = 167) and those with BMI > or = 27 kg/m2 (n = 141),
and for a series of covariance analyses using age, plus height for fat mass (FM)
and fat free mass (FFM), as covariates. A corrected P value (P*) for multiple
tests has been calculated according to P* = 1-(1-P)(number of phenotypes).
MEASUREMENTS: Variables were BMI (in kg/m2), sum of six skinfolds (SF6 in mm), FM
(in kg), percent body fat (%FAT) and FFM (in kg). Polymerase chain react
restricted fragment length polymorphisms PCR-RFLP) was used to identified a K109R
substitution in exon 4, a Q223R in exon 6, a K656N in exon 14 and an automatic
DNA sequencer for a CA microsatellite repeat in intron 3, and heteroduplex
pattern on non-denaturing gel for a CTTT repeat in intron 16. RESULTS: Good
evidence of linkage was observed for Q223R with FM (P = 0.005; P* = 0.02), and
for the CTTT repeat with FFM (P = 0.007; P* = 0.03). Weaker linkages (0.02 < or =
P < or = 0.05) were also observed between Q223R and BMI, SF6 and FFM, between the
CA repeat and BMI, SF6 and FM, and between the CTTT repeat and FM. Moreover, FFM
values were found to be different among genotypes for the CTTT repeat
polymorphism with heavier females, carriers of the 123* allele at the CTTT
repeat, showing 4 kg less of FFM (43.6 +/- 1.0, n = 21 vs 47.7 +/- 0.8, n = 30; P
= 0.005; P* = 0.02) than non-carriers. Also, at the Q223R polymorphism, in lower
BMI males, carriers of the Q223 allele were 4 kg lighter in FFM (53.4 +/- 0.6, n
= 47 vs 56.6 +/- 0.9, n = 18; P = 0.005; P* = 0.02) than non-carriers. No
significant differences were observed between lower and higher BMI subjects in
genotype and allele frequency distributions for any of the polymorphisms.
CONCLUSIONS: These results indicate that the LEPR gene is involved in the
regulation of the body composition in human particularly of FFM in the QFS.
PMID- 10193874
TI - Diet induced thermogenesis measured over 24h in a respiration chamber: effect of
diet composition.
AB - OBJECTIVE: To study the effect of diet composition on diet-induced thermogenesis
(DIT) over 24h in a respiration chamber. SUBJECTS: Eight healthy female
volunteers (age 27 +/- 3 y; body mass index, BMI 23 +/- 3 kg/m2). DIETS: A high
protein and carbohydrate (HP/C) (60:10:30; percentage energy (E%)carbohydrate,
fat and protein, respectively) and high fat (HF) (30:60:10 respectively) diet,
both isoenergetic, isovolumetric, composed of normal food items and matched for
organoleptic properties (taste, smell, appearance). DESIGN: Subjects spent two
36h periods each in a respiration chamber consuming both test diets in random
order. Components of 24h energy expenditure (24h EE): sleeping metabolic rate,
DIT and activity induced energy expenditure were measured. RESULTS: DIT was
higher in all subjects while on the HP/C diet (1295 kJ/d vs 931 kJ/d; 14.6% vs
10.5% of energy intake; P < 0.02). There was no significant difference in other
components or total 24h EE, although there was a trend towards higher EE on the
HP/C diet. CONCLUSION: A high protein and carbohydrate diet induces a greater
thermic response in healthy individuals when compared to a high fat diet.
PMID- 10193875
TI - Mutational analysis of the proopiomelanocortin gene in Caucasians with early
onset obesity.
AB - OBJECTIVE: Mutations in the human gene encoding the polyhormone peptide
proopiomelanocortin (POMC) are associated with obesity in rare cases and the gene
co-localizes with a reported quantitative trait loci (QTL) for variations in
circulating leptin levels and fat mass on human chromosome 2p21. In this study we
have used polymerase chain reaction (PCR) and single strand conformation
polymorphism (SSCP) analysis, to test whether variations in the human POMC gene
are associated with human obesity. DESIGN AND SUBJECTS: Primary mutational
analysis was performed on the coding region of the POMC gene and 500 bp of the
putative promoter region, by single strand conformational analysis and
sequencing, in 56 subjects with juvenile onset obesity (body mass index (BMI) >
or = 31 kg/m2 at the draft board examination). The prevalence of two
polymorphisms were further studied in 156 obese and 205 control subjects, and in
a population based cohort of 380 extensively characterized young healthy
subjects. RESULTS: We have identified a total of six gene variants, five were
silent nucleotide substitutions (No51(promoter) g-->c, No670(5'UTR)g-->a,
No4512(codon6)c-->t Cys/Cys, No7726(codon116)c-->t Leu/Leu) of which one was
prevalent (No8246(3'UTR)c-->t) and one variant changed an amino acid
(No8086(codon236)g-->c Arg/Gln). The amino acid substitution was only seen in one
subject. Comparing the prevalence of the frequent No8246 silent polymorphism, in
an association study comprising 156 subjects with juvenile onset obesity and 205
randomly sampled control subjects (mean BMI 23.5+/-4.7 kg/m2), did not show any
relationship to obesity. Also, comparing the prevalence of a known 9bp
insertion/deletion variant in the coding region of the gene between obese and
lean, showed no association to obesity. Furthermore, analyzing a population based
cohort of 380 young healthy Caucasians for the prevalent 3'UTR polymorphism as
well as the 9 bp insertion/deletion variant did not show any association to
deviations in body fat contents or fasting serum leptin concentrations.
CONCLUSION: In conclusion, it is unlikely that variations in the coding region
and the putative promoter of the POMC gene are a major cause of juvenile onset
human obesity.
PMID- 10193876
TI - Persisting obesity starting before puberty is associated with stable
intraabdominal fat during adolescence.
AB - OBJECTIVES: To observe the evolution of intraabdominal adipose tissue (IAT) in
obese prepubertal children, who did not change their degree of obesity during
adolescence and to evaluate its relationship with metabolic risk indexes (RI).
DESIGN: Longitudinal study of 16 obese adolescents (eight male and eight female)
in whom relative body weight (RBW) did not change significantly and pubertal
development was completed during the study period. MEASUREMENTS: Magnetic
resonance imaging (MRI) scan at lumbar level (L4) three times during a 4 y
period. At basal and at four years biochemical assays for metabolic indexes.
RESULTS: IAT did not differ significantly over the three measurement times and
showed significant correlations between first and second (r = 0.66, P < 0.005),
first and third (r = 0.61, P < 0.01) and second and third values (r = 0.84, P <
0.0001). Subcutaneous adipose tissue (SAT) increased significantly from basal to
third evaluation (P < 0.002). At baseline, IAT correlated significantly with
lipids (total and LDL cholesterol r = 0.72, P < 0.004), while at the end of the
study, IAT correlated positively with insulin (fasting insulin r = 0.55, P <
0.008, insulin area after oral glucose tolerance test (OGTT) r = 0.60, P < 0.03,
fasting insulin/glucose r = 0.67 P < 0.006) and negatively with high density
lipoprotein (HDL) cholesterol (r = -0.55, P < 0.04). CONCLUSIONS: Obesity
achieved before puberty, and stable during adolescence, showed a relatively
stable amount of IAT. In post pubertal children the relationship of IAT to
clinically significant risk factors resemble the pattern in obese adults.
PMID- 10193877
TI - Energy intake and appetite are suppressed by glucagon-like peptide-1 (GLP-1) in
obese men.
AB - BACKGROUND: Peripheral administration of glucagon-like peptide-1 (GLP-1) for four
hours, to normal weight and obese humans, decreases food intake and suppresses
appetite. OBJECTIVE: The aim of this study was to assess the effect of an eight
hour infusion of GLP-1 on appetite and energy intake at lunch and dinner in obese
subjects. DESIGN: Randomised, blinded cross-over design with intravenous infusion
of GLP-1 (0.75 pmol x kg(-1) min(-1)) or saline. SUBJECTS: Eight obese (body mass
index, BMI, 45.5 +/- 2.3 kg/m2) male subjects. MEASUREMENTS: Ad libitum energy
intake at lunch (12.00 h) and dinner (16.00 h) after an energy fixed breakfast
(2.4 MJ) at 08.00 h. Appetite sensations using visual analogue scales, (VAS)
immediately before and after meals and hourly in-between. Blood samples for the
analysis of glucose, insulin, C-peptide, GLP-1 and peptide YY. Gastric emptying
after breakfast and lunch using a paracetamol absorption technique. RESULTS:
Hunger ratings were significantly lower with GLP-1 infusion. The summed ad
libitum energy intake at lunch and dinner was reduced by 1.7 +/- 0.5 MJ (21 +/-
6%) by GLP-1 infusion (P = 0.01). Gastric emptying was delayed by GLP-1 infusion,
and plasma glucose concentrations decreased (baseline: 6.6 +/- 0.35 mmol/L;
nadir: 5.3 +/- 0.15 mmol/L). No nausea was recorded during GLP-1 infusion.
CONCLUSIONS: Our results demonstrate that GLP-1 decreases feelings of hunger and
reduces energy intake in obese humans. One possible mechanism for this finding
might be an increased satiety primarily mediated by gastric vagal afferent
signals.
PMID- 10193878
TI - Gender difference in the effect of body composition on energy metabolism.
AB - OBJECTIVE: The aim of this study was to investigate the relationship between
energy expenditure (EE) and fat mass (FM) by using a cross-sectional approach to
study the linear relationship between body composition variables and EE
phenotypes as well as an intervention design to investigate the effect of body
weight loss on energy metabolism in both genders. METHODS: The correlations and
linear relationships between body weight, FM, fat-free mass (FFM) and abdominal
fat vs 24 h EE (EE 24) and sleeping metabolic rate (SMR) were compared between 65
men and 35 women, and before and after weight loss in 10 men and 10 women.
RESULTS: Our results showed that for a given FM, men displayed a higher EE than
women, independently of FFM. Furthermore, regression analysis revealed that after
body weight loss, men displayed a lower SMR for a given FM or FM adjusted for FFM
compared to before the treatment, but this was not so in women. However, when FM
was adjusted for abdominal fat deposition, the difference between the conditions
was no longer observed. CONCLUSIONS: FM has a significant impact on EE only in
men. We suggest that abdominal adipose tissue may exert a potent regulatory
effect on energy metabolism which would be more detectable in men who generally
store more fat in this compartment than women.
PMID- 10193879
TI - Is dieting good for you?: Prevalence, duration and associated weight and
behaviour changes for specific weight loss strategies over four years in US
adults.
AB - OBJECTIVES: This present study describes weight control strategies used by a
heterogeneous sample of US adults and their associations with weight and
behaviour change over time. DESIGN: A prospective cohort study. PARTICIPANTS:
Participants for this study were 1120 US adults recruited from the community who
enrolled in a three-year intervention study to examine methods for preventing age
related weight gain. MEASURES: Measured body weight and self-reported behaviours
related to body weight (dieting practices, dietary intake and physical activity)
were completed annually for four years. RESULTS: Over 70% reported using each of
the following dieting strategies at least once in four years: increase exercise
(82.2%); decrease fat intake (78.7%); reduce food amount (78.2%); and reduce
calories (73.2%). Cumulative duration of use of these behaviours was brief (for
example, even the most common behaviours were used only 20% of the time). Global
reports of dieting were not predictive of weight change over time. However, a
dose-response relationship was observed between reported duration of use of
several specific weight loss strategies over the four years and change in
behaviours and weight gain. CONCLUSIONS: These findings suggest that public
health recommendations for weight control may need to place greater emphasis on
persistence of weight control behaviours.
PMID- 10193880
TI - Healthcare professional's demand for knowledge in informatics.
AB - OBJECTIVE: To develop an economic model of health care professional demand for
knowledge capital in health informatics. DESIGN: Case study with application of
the contingent valuation method to develop a small-scale model. SETTING:
Specialized clinic at a university Hospital in Sweden. RESULTS: The model
displays the economic rationale behind an individual choice to spend leisure time
for obtaining knowledge in health informatics. This decision reduces the total
leisure time, but does not increase salary. Instead, it may increase the personal
well-being by higher satisfaction gained from using information systems and by
being recognized as a computer expert. CONCLUSIONS: Individuals have preferences
over all uses of time and for activities they can choose to engage in. Support of
health care staff's investment in health informatics knowledge capital may
benefit both the individuals and indirectly the health care organization.
PMID- 10193881
TI - Using information systems to measure and improve quality.
AB - Information systems (IS) are increasingly important for measuring and improving
quality. In this paper, we describe our integrated delivery system's plan for and
experiences with measuring and improving quality using IS. Our belief is that for
quality measurement to be practical, it must be integrated with the routine
provision of care and whenever possible should be done using IS. Thus, at one
hospital, we now perform almost all quality measurement using IS. We are also
building a clinical data warehouse, which will serve as a repository for quality
information across the network. However, IS are not only useful for measuring
care, but also represent powerful tools for improving care using decision
support. Specific areas in which we have already seen significant benefit include
reducing the unnecessary use of laboratory testing, reporting important
abnormalities to key providers rapidly, prevention and detection of adverse drug
events, initiatives to change prescribing patterns to reduce drug costs and
making critical pathways available to providers. Our next major effort will be
introduce computerized guidelines on a more widespread basis, which will be
challenging. However, the advent of managed care in the US has produced strong
incentives to provide high quality care at low cost and our perspective is that
only with better IS than exist today will this be possible without compromising
quality. Such systems make feasible implementation of quality measurement, care
improvement and cost reduction initiatives on a scale which could not previously
be considered.
PMID- 10193882
TI - UMLS-based access to CPR data. Unified Medical Language Systems.
AB - This paper describes the results of a project that explores the use the Unified
Medical Language System (UMLS) for knowledge-driven tasks, such as browsing a
computer-based patient record (CPR). The project consisted of a number of steps:
the mapping between CPR terms and UMLS concepts, the development of an algorithm
that explores the CPR data using this mapping and the implementation of a first
prototype browser that visualizes 'found' data. A second task addressed in this
project has been the direct access to online medical literature (MEDLINE) using
the UMLS concepts found in the CPR data. In this project, we used a preliminary
version of the Open Records for Patient Care (ORCA) CPR that consisted only of
the history and physical examination data of patient suffering from heart
failure.
PMID- 10193883
TI - Shared care for diabetes: supporting communication between primary and secondary
care.
AB - OBJECTIVE: To assess the effects on information exchange of electronic
communication between physicians co-treating diabetic patients. DESIGN:
Comparison of traditional paper-based communication for reporting and electronic
communication. SETTING: General practitioners and an internal medicine outpatient
clinic of an urban public hospital. SUBJECTS: A total of 275 diabetic patients,
and the 32 general practitioners and one internal medicine consultant who cared
for them. INTERVENTION: An electronic communication network, linking up the
computer-based patient records of the physicians, thus enabling electronic data
interchange. MAIN OUTCOME MEASURES: Number of letters sent and received per year
by the general practitioners, the number of diabetes-related parameters (e.g.
results of laboratory tests) in the patient records, and HBA1C levels. RESULTS:
INTERVENTION GPs received more messages per year (1.6 per patient) than control
GPs (0.5 per patient, P<0.05). Significant higher availability (P<0.05) was
achieved for data on HBA1C levels, fructosamine levels, blood pressure
measurements, cholesterol levels, triglyceride levels and weight measurements.
INTERVENTION patients showed a slight but significant decrease of HBA1C levels in
the second semester of 1994 (from 7.0 to 6.8, P = 0.03), control patients also
showed a slightly decreased group mean, but this change was not significant (from
6.6 to 6.5, P = 0.52). The magnitudes of these mean differences, however, were
not significantly different (intervention group: 0.21; control group: 0.12, P =
0.68). CONCLUSIONS: The electronic communication network for exchanging
consultation outcomes significantly increased frequency of communication and the
availability of data to the general practitioner on diagnostic procedures
performed in the hospital, thus providing more complete information about the
care that patients are receiving. A large-scale experiment over a longer period
of time is needed to assess the effects of improved communication on quality of
care.
PMID- 10193884
TI - Dynamic workflow model for complex activity in intensive care unit.
AB - Co-operation is very important in Medical care, especially in the Intensive Care
Unit (ICU) where the difficulties increase which is due to the urgency of the
work. Workflow systems are considered as well adapted to modelize productive work
in business process. We aim at introducing this approach in the Health Care
domain. We have proposed a conversation-based workflow in order to modelize the
therapeutics plan in the ICU [1]. But in such a complex field, the flexibility of
the workflow system is essential for the system to be usable. We have
concentrated on three main points usually proposed in the workflow models,
suffering from a lack of dynamicity: static links between roles and actors,
global notification of information changes, lack of human control on the system.
In this paper, we focus on the main points used to increase the dynamicity. We
report on affecting roles, highlighting information, and controlling the system.
We propose some solutions and describe our prototype in the ICU.
PMID- 10193885
TI - Current and future models for nursing e-journals: making the most of the Web's
potential.
AB - We are presently witnessing an increasing number of nursing, medical and health
related electronic journals (e-journals) being made available on the World Wide
Web, a minority of which are specifically devoted to informatics. We would
expect, given the potential of interacting multimedia and computer-mediated
communications (i.e. telematics), to also see an increasing diversity of models,
but this is not currently the case. Following a brief discussion of some of the
issues relevant to electronic publications, the authors present a taxonomy of
current nursing e-journal models, including discussion of some examples from
around the world that fall into categories within this taxonomy. We describe the
model and levels of usage of one particular e-journal, Nursing Standard Online.
Some of the issues presented may account for the current relative paucity of high
quality content and innovative models in the development of Web-based e-journals
for nurses and other health professionals. We believe it likely that nursing e
journals using current models will need to be specialist rather than generalist
if they are to attract a larger audience. In concluding our paper, we advocate
the development of innovative and increasingly interactive nursing e-journals as
the way forward, discussing one particular model which holds promise.
PMID- 10193886
TI - Building a flexible protocol information system with ready for use' web
technology.
AB - This paper describes how web technology, currently available, can be used to
build a fast and easy flexible protocol information system. The interface design
and functionalities of the system were based on experiences with a previous
version of a protocol information system (ProtoVIEW). A wide range of diagnostic
or therapeutic protocols could be retrieved and viewed with ProtoVIEW. The Web
based version contains all functionalities of the non web-based version plus
several new functionalities. The web version contains an X-ray viewer and a great
deal of interactivity such as validation of electronic patient data forms. The
most important additional function is the context sensitive protocol support that
may lead to improved protocol adherence. Finally, the web-based version can be
accessed from any working place since patient data and protocols are stored
centrally.
PMID- 10193887
TI - Natural language generation of surgical procedures.
AB - A number of compositional Medical Concept Representation systems are being
developed. Although these provide for a detailed conceptual representation of the
underlying information, they have to be translated back to natural language for
used by end-users and applications. The GALEN programme has been developing one
such representation and we report here on a tool developed to generate natural
language phrases from the GALEN conceptual representations. This tool can be
adapted to different source modelling schemes and to different destination
languages or sublanguages of a domain. It is based on a multilingual approach to
natural language generation, realised through a clean separation of the domain
model from the linguistic model and their link by well defined structures.
Specific knowledge structures and operations have been developed for bridging
between the modelling 'style' of the conceptual representation and natural
language. Using the example of the scheme developed for modelling surgical
operative procedures within the GALEN-IN-USE project, we show how the generator
is adapted to such a scheme. The basic characteristics of the surgical procedures
scheme are presented together with the basic principles of the generation tool.
Using worked examples, we discuss the transformation operations which change the
initial source representation into a form which can more directly be translated
to a given natural language. In particular, the linguistic knowledge which has to
be introduced--such as definitions of concepts and relationships is described. We
explain the overall generator strategy and how particular transformation
operations are triggered by language-dependent and conceptual parameters. Results
are shown for generated French phrases corresponding to surgical procedures from
the urology domain.
PMID- 10193888
TI - Towards specialised middleware for healthcare information systems.
AB - Middleware is now a commonly used expression and anyone building distributed
applications is referring to 'middleware services'. Nevertheless this notion
lacks of sound theoretical foundation. This paper tries to clarify the
relationship between the components of distributed environments, especially in
healthcare and to establish some classification aiming at gaining a common
understanding of the functionality and interdependency of the existing modules of
distributed environments. A case study is presented and the potential benefits of
using a middleware approach are discussed.
PMID- 10193889
TI - Standard Generalized Markup Language for self-defining structured reports.
AB - Structured reporting is the process of using standardized data elements and
predetermined data-entry formats to record observations. The Standard Generalized
Markup Language (SGML; International Standards Organization (ISO) 8879:1986)--an
open, internationally accepted standard for document interchange was used to
encode medical observations acquired in an Internet-based structured reporting
system. The resulting report is self-documenting: it includes a definition of its
allowable data fields and values encoded as a report-specific SGML document type
definition (DTD). The data-entry forms, DTD, and report document instances are
based on report specifications written in a simple, SGML-based language designed
for that purpose. Reporting concepts can be linked with those of external
vocabularies such as the Unified Medical Language System (UMLS) Metathesaurus.
The use of open standards such as SGML is an important step in the creation of
open, universally comprehensible structured reports.
PMID- 10193890
TI - Global healthcare and the flux of technology.
AB - For Medinfo '98, as an exercise in technological forecasting and analysis, we
volunteered to project the direction of healthcare informatics into the next
century. This paper is an extended discussion of that presentation. We open with
the observation that healthcare informatics is merely one of the many endeavors
that is following a turbulent but nearly inescapable path into a digital future.
Our objective is to describe as best we can the overall geography of the general
path we appear to be on, to anticipate some of our future checkpoints along the
way, to identify some of the roughest transitional passages as they apply to
healthcare, and to present this as one guide among many to those who have offered
to do the steering into this exciting, electronic unknown. Emphasis is placed on
the growing importance of information networks, the particular nature of
complexity as applied to healthcare communications and healthcare itself, and the
impact of the rising costs of what is medically possible in a technological age.
Certain evident recent changes in computing technology are singled out for their
present and expected importance. The whole is considered from a broader
organizational perspective to better understand the turbulence of present times,
and what medical informatics might address to ameliorate the most onerous
healthcare issues.
PMID- 10193891
TI - Virtual planning of liver resections: image processing, visualization and
volumetric evaluation.
AB - Operability of a liver tumor depends on its three dimensional relation to the
intrahepatic vascular trees as well as the volume ratio of healthy to tumorous
tissue. Precise operation planning is complicated by anatomic variability and
distortion of the vascular trees by the tumor or preceding liver resections. We
have developed a computer based 3D virtual operation planning system which is
ready to go in routine use. The main task of a system in this domain is a
quantifiable patient selection by exact prediction of post-operative liver
function. It provides the means to measure absolute and relative volumes of the
organ structures and resected parenchyma. Another important step in the pre
operative phase is to visualize the relation between the tumor, the liver and the
vessel trees for each patient. The new 3D operation planning system offers
quantifiable liver resection proposals based on individualized liver anatomy. The
results are presented as 3D movies or as interactive visualizations as well as in
quantitative reports.
PMID- 10193893
TI - Medical multiparametric time course prognoses applied to kidney function
assessments.
AB - In this paper, we describe an approach to utilize case-based reasoning methods
for trend prognoses for the monitoring of the kidney function in an Intensive
Care Unit (ICU) setting. Since using conventional methods for reasoning over time
does not fit for course predictions with poor medical knowledge of typical course
patterns, we have developed abstraction methods suitable for integration into our
case-based reasoning system ICONS. These methods combine medical experience with
prognoses of multiparametric courses. On the ICU, the monitoring system NIMON
provides a daily report based on current measured and calculated kidney function
parameters. Subsequently, we generate course-characteristic trend descriptions of
the renal function over the course of time. Using case-based reasoning retrieval
methods, we search in the case base for courses similar to the current trend
descriptions. Finally, we present the current course together with similar
courses as comparisons and as probable prognoses to the user. We applied case
based reasoning methods in a domain which seemed reserved for statistical methods
and conventional temporal reasoning.
PMID- 10193892
TI - Measurement and classification of retinal vascular tortuosity.
AB - Automatic measurement of blood vessel tortuosity is a useful capability for
automatic ophthalmological diagnostic tools. We describe a suite of automated
tortuosity measures for blood vessel segments extracted from RGB retinal images.
The tortuosity measures were evaluated in two classification tasks: (1)
classifying the tortuosity of blood vessel segments and (2) classifying the
tortuosity of blood vessel networks. These tortuosity measures were able to
achieve a classification rate of 91% for the first problem and 95% on the second
problem, which confirms that they capture much of the ophthalmologists' notion of
tortuosity. Finally, we discuss how the accuracy of these measures can be
influence by the method used to extract the blood vessel segments.
PMID- 10193894
TI - Extending a teleradiology system by tools for visualization and volumetric
analysis through a plug-in mechanism.
AB - This paper describes ongoing research concerning interactive volume visualization
coupled with tools for volumetric analysis. To establish an easy to use
application, the three-dimensional-visualization has been embedded in a state of
the art teleradiology system, where additional functionality is often desired
beyond basic image transfer and management. Major clinical requirements for
deriving spatial measures are covered by the tools, in order to realize extended
diagnosis support and therapy planning. Introducing a general plug-in mechanism,
this work exemplarily describes the useful extension of an approved application.
Interactive visualization was achieved by a hybrid approach taking advantage of
both the precise volume visualization based on the Heidelberg ray-tracing model
and the graphics acceleration capabilities of modern workstations. Several tools
for volumetric analysis extend the three-dimensional-viewing. They are controlled
by adequate input devices to select locations in the data volume, measure
anatomical structures or initiate a segmentation process. Moreover, a haptic
interface can be connected to provide a more realistic feedback while navigating
within the three-dimensional-reconstruction. The work is closely related to
research in the field of heart, liver and head surgery. In cooperation with our
medical partners the development of tools as presented facilitates the
integration of image analysis into the clinical routine.
PMID- 10193895
TI - Transgenic animals relevant to Alzheimer's disease.
AB - This article reviews the functional studies that have been carried out on
transgenic and knockout animals that are relevant to Alzheimer's disease (AD).
The discussion focuses upon the functional characterisation of these strains,
particularly upon factors that affect synaptic processes that are thought to
contribute to memory formation, including hippocampal long-term potentiation. We
examine the use of transgenes associated with amyloid precursor protein and
presenilin-1, their mutations linked to early onset familial AD, and the recent
attempts to establish double transgenic strains that have an AD-like pathology
which occurs with a more rapid onset. The development of new transgenic strains
relevant to Alzheimer's disease has rapidly outpaced their characterisation for
functional deficits in synaptic plasticity. To date most studies have focused on
those transgenes linked to the minority of familial early onset rather than late
onset sporadic AD cases, and have focused on those changes linked to the
induction of the early-phase of hippocampal long-term potentiation. Future
studies will need to address the question of whether the development of AD
pathology can be reversed or at least halted and this will be aided by the use of
conditional transgenics in which genes linked to AD can either be switched on or
off later in development. Furthermore, it remains to be resolved whether the
deficits in synaptic function are specific to the hippocampus and whether
deficits affect late-phase long-term potentiation. Nonetheless, the recent
advances in genome sciences and the development of transgenic technology have
provided a unique opportunity to study how genes associated with human cognitive
dysfunction alter synaptic transmission between neurones in the mammalian brain.
PMID- 10193896
TI - Electrophysiological characterisation of the human N-type Ca2+ channel III: pH
dependent inhibition by a synthetic macrocyclic polyamine.
AB - The effects of a novel synthetic macrocyclic polyamine (LY310315) were
investigated on recombinant human N-type Ca2+ channels stabley expressed in
HEK293 cells. LY310315 proved to be a potent and reversible N-type Ca2+ channel
antagonist. Inhibition by this compound was dose-dependent with an IC50 of
approximately 0.4 microM at pH 7.35. LY310315 blocked very rapidly at all
concentrations tested. Upon washout, recovery of the Ca2+ current developed with
a time constant of approximately 30 s. Use-dependence in the development of block
indicated that voltage-dependent transitions in the channel protein were required
to permit significant inhibition. Application of > 100 times the IC50 dose of
LY310315 to the interior of the cell produced no detectable Ca2+ current
inhibition. LY310315 had no effects on the kinetics of channel activation or
deactivation but did slightly slow the rate of macroscopic inactivation observed
during a 300 ms test depolarisation. In the presence of LY310315 the activation
curve was significantly shallower. This resulted in a shift in the activation
midpoint voltage to a more depolarised levels. LY310315-induced inhibition of
human N-type channels was strongly dependent on the extracellular pH, with
increased potency seen upon extracellular acidification. Although most effective
against N-type Ca2+ channels, LY310315 was also found to inhibit both P-type and
L-type Ca2+ channels. LY310315 proved to be a weak blocker of Na+ currents, but
produced approximately 50% of the K+ currents of AtT20 cells at a concentration
of 0.5 microM.
PMID- 10193898
TI - Effects of pregnanolone on behavioural parameters and the responses to GABA(A)
receptor antagonists in the late gestation fetal sheep.
AB - Placental progesterone metabolites may suppress fetal behaviour by interacting
with GABA(A) receptors. In an initial study, the effect of 5beta-pregnan-3alpha
ol-20-one (pregnanolone) given as a bolus (2.5 and 5.0 mg) or infused at a rate
of 25 mg/h was investigated in unanaesthetized, catheterized fetal sheep, 127-135
days gestation. The incidence of fetal breathing movements (FBM) and behavioural
arousal activity, defined as nuchal muscle electromyographic (EMG) activity
during low voltage electrocortical (LV ECoG) activity were suppressed by
pregnanolone administered as a bolus, while the pregnanolone infusion produced a
significant decrease in arousal and EOG activity, and an increase in the presence
of HV ECoG. The effect of pregnanolone on fetal behaviour and arousal induced by
the GABA(A) antagonist picrotoxin was also investigated. Picrotoxin was given as
a bolus (approximately 300 microg/kg) and pregnanolone was subsequently
administered as a bolus (5.0 mg), and behavioural parameters were recorded and
analysed. The incidence of arousal and FBM were 1.1 +/- 1.6 min/10 min and 2.5 +/
2.3 min/10 min, respectively, before picrotoxin treatment and increased during
the 10-20 and 20-30 min epochs after picrotoxin treatment (arousal: 5.0 +/- 2.2
and 6.5 +/- 3.6 min/10 min, respectively, n = 6, P < 0.05; FBM: 7.3 +/- 3.2 and
9.3 +/- 1.2 min/10 min, respectively, n = 6, P < 0.05). The picrotoxin-induced
increases in arousal and FBM were significantly suppressed (n = 6, P < 0.05) by
pregnanolone treatment to 1.6 +/- 1.5 min/10 min and 4.6 +/- 2.3 min/10 min,
respectively. We conclude that; (i) the GABA(A) active steroid pregnanolone
suppresses basal and picrotoxin-induced fetal arousal and FBM; and (ii) steroid
sensitive GABA(A) receptors may regulate fetal behaviour and breathing.
PMID- 10193897
TI - Inhibition of receptor-mediated calcium responses by corticotrophin-releasing
hormone in the CATH.a cell line.
AB - A region of the brain believed to be important in the CNS response to stress is
the locus coeruleus, the predominant site of noradrenergic cell bodies.
Corticotrophin releasing hormone (CRH) is the primary hypothalamic releasing
hormone responsible for the activation of the pituitary-adrenal axis in response
to stress and, in this study, we employed a locus coeruleus-like cell line,
CATH.a, to investigate the modulation of receptor signalling pathways by CRH.
Pituitary adenylyl cyclase-activating polypeptide (PACAP) (10 nM), vasoactive
intestinal peptide (VIP) (1 microM) and carbachol (1 mM) produced transient
increases in intracellular [Ca2+]. The inhibition of the carbachol (1 mM)
response by CRH was concentration-dependent (EC50 = 154 +/- 1.8 nM). Calcium
responses to sub-maximally effective concentrations of PACAP (5 nM), VIP (400 nM)
and carbachol (1 mM) were abolished by prior exposure to CRH (1 microM). At the
concentrations employed, CRH and VIP both substantially increased intracellular
[3H]-cyclic AMP accumulation. The adenylyl cyclase activator forskolin (10
microM) was also effective at eliminating the agonist-induced calcium responses.
Incubation with the cell permeant cyclic AMP analogue dibutyryl cyclic AMP
(dbcAMP) (1 mM), an activator of protein kinase A (PKA), for 12 min prior to
agonist exposure similarly abolished the intracellular calcium response to
carbachol. Carbachol increased [3H]-inositol phosphate ([3H]-IP) accumulation to
a maximum of 2.4 +/- 0.11-fold basal (EC50 = 6.75 +/- 0.26 microM). PACAP
produced a much greater accumulation (19.9 +/- 2.1 fold basal; EC50 = 24 nM). In
the presence of forskolin (10 microM), neither carbachol- nor PACAP-induced [3H]
IP accumulation was significantly different from in its absence. These results
demonstrate that CRH inhibits receptor-mediated intracellular calcium responses
in a locus coeruleus-like cell line possibly via activation of PKA. This
modulation could be important in controlling neuronal function in vivo in
stressful situations in which the levels of CRH are increased in the locus
coeruleus.
PMID- 10193899
TI - Chronic treatment with oestradiol does not alter in vitro LTP in subfield CA1 of
the female rat hippocampus.
AB - Population excitatory post-synaptic potentials (pEPSPs) were recorded in vitro
from subfield CA1 of the hippocampus of female rats which had been ovariectomized
and treated for 14 days with either oil or 17beta-oestradiol (10 microg/day). The
currents applied to the Schaffer collateral-commissural input necessary to induce
threshold, maximum and 50% maximum pEPSP responses did not differ between groups.
Application of trains of pulses (0.1-1 s; 100 Hz) evoked post-tetanic and long
term (> 60 min) potentiation of pEPSP responses, the magnitude of which was
related to stimulus duration in both groups. However, the degree of potentiation
induced by near-threshold (0.1, 0.15 and 0.2 s) and saturating (1 s) stimuli did
not differ between groups. Thus, despite reports that oestradiol can modulate
synaptic spine density and glutamatergic and GABAergic components of the inputs
to CA1, these data suggest that chronic oestradiol treatment has no effect on
either the excitability or induction of LTP in the Schaffer collateral
commissural-CA1 pathway.
PMID- 10193900
TI - Activation of mGluRII induces LTD via activation of protein kinase A and protein
kinase C in the dentate gyrus of the hippocampus in vitro.
AB - The involvement of metabotropic glutamate receptor group II (mGluRII) in the
induction of long-term depression (LTD) was investigated in the medial perforant
path of the rat dentate gyrus, a region with a very high density of mGluRII.
Perfusion of either of two potent mGluRII agonists, (2S,1R,2R,3R)-2-(2S, 1'R,
2'R, 3'R)-2 (2' 3'-dicarboxycyclopropyl)glycine (DCG-IV) or (+)-2-
aminobicyclo[3.1.0]hexane-2-6-dicarboxylic acid (LY354740) induced a reversible
inhibition of the field EPSP followed, upon washout of the agonist, by LTD. The
reversible inhibition was associated with a change in paired pulse depression,
indicating an underlying presynaptic reduction in the probability of transmitter
release, whereas the LTD was not associated with a change in paired pulse
depression, indicating either a presynaptic reduction in the number of active
release sites, or a postsynaptic change. Further evidence that the DCG-IV-induced
LTD was generated by activation of mGluRII was the finding that the mGluRII
antagonist (RS)-alpha-methylserine-O-phosphate monophenylphosphoryl ester
(MSOPPE) prevented the induction of the LTD induced by DCG-IV. The DCG-IV-induced
LTD showed mutual occlusion with LFS-induced LTD. The generation of the agonist
induced LTD required, in part, activation of N-methyl-D-aspartate receptors
(NMDAR), as LTD induction was partially blocked in the presence of the NMDAR
antagonist D-2-amino-5-phosphonopentanoate (AP5). Evidence for involvement of
protein kinase C (PKC) and protein kinase (PKA) in the induction of LTD by
activation of mGluRII was obtained by showing an inhibition of the DCG-IV-induced
LTD by the PKC inhibitors Ro-31-8220 and bisindolylmaleimide I, and also by the
PKA inhibitor H-89. The study demonstrates that activation of mGluRII induces LTD
via activation the PKA and PKC pathways in the medial perforant path of the
dentate gyrus.
PMID- 10193901
TI - Amino-alkyl-cyclohexanes are novel uncompetitive NMDA receptor antagonists with
strong voltage-dependency and fast blocking kinetics: in vitro and in vivo
characterization.
AB - The present study characterized the in vitro NMDA receptor antagonistic
properties of novel amino-alkyl-cyclohexane derivatives and compared these
effects with their ability to block excitotoxicity in vitro and MES-induced
convulsions in vivo. The 36 amino-alkyl-cyclohexanes tested displaced [3H]-(+)-MK
801 binding to rat cortical membranes with K(i)s between 1.5 and 143 microM.
Current responses of cultured hippocampal neurones to NMDA were antagonized by
the same compounds with a wide range of potencies (IC50s of 1.3-245 microM, at
70 mV) in a use- and strongly voltage-dependent manner (delta 0.55-0.87). The
offset kinetics of NMDA receptor blockade was correlated with equilibrium
affinity (Corr Coeff. 0.87 P < 0.0001). As an example, MRZ 2/579 (1-amino
1,3,3,5,5-pentamethyl-cyclohexane HCl) had similar blocking kinetics to those
previously reported for memantine (K(on) 10.67 +/- 0.09 x 10(4) M(-1) s(-1),
K(off) 0.199 +/- 0.02 s(-1), K(d) = K(off)/K(on) = 1.87 microM c.f. IC50 of 1.29
microM). Most amino-alkyl-cyclohexanes were protective against glutamate toxicity
in cultured cortical neurones (e.g. MRZ 2/579 IC50 2.16 +/- 0.03 microM).
Potencies in the three in vitro assays showed a relatively strong cross
correlation (all corr. coeffs. > 0.72, P < 0.0001). MRZ 2/579 was also effective
in protecting hippocampal slices against 7 min. hypoxia/hypoglycaemia-induced
reduction of fEPSP amplitude in CA1 with an EC50 of 7.01 +/- 0.24 microM. MRZ
2/579 showed no selectivity between NMDA receptor subtypes expressed in Xenopus
oocytes but was somewhat more potent than in patch clamp experiments-IC50s of
0.49 +/- 0.11, 0.56 +/- 0.01 microM, 0.42 +/- 0.04 and 0.49 +/- 0.06 microM on
NR1a/2A /2B, /2C and 2/D, respectively. In contrast, memantine and amantadine
were both 3-fold more potent at NR1a/2C and NR1a/2D than NR1a/2A receptors. All
Merz amino-alkyl-cyclohexane derivatives inhibited MES-induced convulsions in
mice with ED50s ranging from 3.6 to 130 mg/kg i.p. The in vivo and in vitro
potencies correlated indicating similar access of most compounds to the CNS. MRZ
2/579 administered at 10 mg/kg resulted in peak plasma concentrations of 5.3 and
1.4 microM following i.v. and p.o. administration respectively, which then
declined with a half life of around 170-210 min. Analysis of A.U.C.
concentrations indicates a p.o./i.v. bioavailability ratio for MRZ 2/579 of 60%.
MRZ 2/579 injected i.p. at a dose of 5 mg/kg resulted in peak brain extracellular
fluid (ECF) concentrations of 0.78 microM (brain microdialysates). Of the
compounds tested MRZ 2/579, 2/615, 2/632, 2/633, 2/639 and 2/640 had affinities,
kinetics and voltage-dependency most similar to those of memantine and had good
therapeutic indices against MES-induced convulsions. We predict that these amino
alkyl-cyclohexanes, which all had methyl substitutions at R1, R2, and R5, at
least one methyl or ethyl at R3 or R4 and a charged amino-containing substitution
at R6, could be useful therapeutics in a wide range of CNS disorders proposed to
involve disturbances of glutamatergic transmission.
PMID- 10193902
TI - GlycineB antagonists and partial agonists in rodent models of Parkinson's disease
-comparison with uncompetitive N-methyl-D-aspartate receptor antagonist.
AB - Antiparkinsonian-like activity of glutamate receptor antagonists (mostly of N
methyl-D-aspartate (NMDA) receptors) has been demonstrated in animals and for
uncompetitive agents, also in humans. In the present study we investigated the
potential antiparkinsonian-like activity of compounds acting at the glycine site
of the NMDA receptor complex in three animal models of Parkinson's disease and
compared them with the new uncompetitive NMDA receptor antagonist MRZ 2/579.
Haloperidol-induced catalepsy was inhibited by the Merz glycine site antagonists
MRZ 2/570, MRZ 2/571 and MRZ 2/576 but not by another antagonist L-701,324 or the
glycine site partial agonists ACPC and D-CS. None of the tested glycine site
antagonists or partial agonists increased locomotor activity or potentiated L
DOPA responses in reserpine and alpha-MT treated rats. In rats with a unilateral
6-OHDA medial forebrain bundle lesion neither glycine site antagonists nor
partial agonists affected rotations on their own or enhanced the contralateral
rotations induced by L-DOPA. In contrast, the uncompetitive NMDA receptor
antagonist MRZ 2/579 was active in all antiparkinsonian tests used in this study.
Based on the present data the therapeutic potential of the glycine site
antagonists and partial agonists tested for the treatment of Parkinson's disease
is rather doubtful. Uncompetitive NMDA receptor antagonists seem to possess a
better profile as antiparkinsonian agents.
PMID- 10193903
TI - Differential actions of dizocilpine (MK-801) on the mesolimbic and mesocortical
dopamine systems: role of neuronal activity.
AB - The significance of impulse activity in the dopamine neurons of the ventral
tegmental area for the dopamine release evoked by systemic administration of the
psychotomimetic drug dizocilpine (MK-801) was investigated. Dual probe
microdialysis was utilized in freely moving rats implanted with one probe in the
ventral tegmental area and a second ipsilateral probe in either the nucleus
accumbens or the medial prefrontal cortex. Dialysates were analyzed with high
performance liquid chromatography with electrochemical detection for dopamine.
The ventral tegmental area was perfused with the sodium channel blocker
tetrodotoxin (1 microM) or vehicle (perfusion solution). A total of 2 h after the
onset of tetrodotoxin perfusion of the ventral tegmental area, MK-801 (0.1 mg/kg)
was injected subcutaneously. Tetrodotoxin perfusion of the ventral tegmental area
significantly reduced dialysate levels of dopamine both in the nucleus accumbens
and the medial prefrontal cortex to approximately 30% of baseline. When given
alone, MK-801 caused a significant, i.e. 50%, increase in extracellular dopamine
levels in the nucleus accumbens, and an even larger increase in the medial
prefrontal cortex, i.e. 150%. Tetrodotoxin perfusion of the ventral tegmental
area completely blocked the systemic MK-801 induced increase in extracellular
concentrations of dopamine in the nucleus accumbens. However, the MK-801-evoked
increase in dopamine levels in the medial prefrontal cortex was not significantly
affected. Thus, the present results allow the conclusion that basal dopamine
output in mesolimbic and mesocortical dopamine nerve terminal regions is
predominantly dependent on nerve impulses generated in the ventral tegmental
area. Moreover, also the MK-801 evoked dopamine release in the mesolimbic
projection is almost entirely dependent on the impulse activity of the dopamine
neurons, in agreement with our previous results. However, the MK-801 evoked
dopamine release in the mesocortical projection is, in contrast, largely
independent of the nerve impulse activity in the dopamine cells. The dysfunctions
of mesolimbic and mesocortical dopamine neurons induced by systemic
administration of non-competitive NMDA receptor antagonists may have direct
bearing on the neurobiology of psychotic states, in particular as regards the
generation of emotional and cognitive impairments.
PMID- 10193904
TI - Adenosine A2A and group I metabotropic glutamate receptors synergistically
modulate the binding characteristics of dopamine D2 receptors in the rat
striatum.
AB - There is experimental evidence for the existence of interactions between
metabotropic glutamate (mGlu), adenosine and dopamine receptors in the striatum.
In membrane preparations from rat striatum the group I and II mGlu receptor
agonist 1-aminocyclopentane-1S-3R-dicarboxylic acid (1S-3R-ACPD) was found to
modulate the binding characteristics of D2 receptors in a similar manner as the
A2A receptor agonist 2-[p-(2-carboxyethyl)phenthylamino]-5'-N
ethylcarboxamidoadenosine (CGS 21680), with a significant decrease in the
affinity of the high-affinity state of D2 receptors for dopamine. The effect of
1S-3R-ACPD was mimicked by (+/-)-trans-ACPD (t-ACPD; a racemic mixture of 1S-3R
ACPD and its inactive isomer 1R-3S-ACPD) and by the selective group I mGlu
receptor agonist 3,5-dihydroxyphenylglycine (DHPG) and it was counteracted by the
selective group I mGlu receptor antagonist 1-aminoindan-1,5-dicarboxilic acid
(AIDA), but not by the the group II and III mGlu receptor antagonist (RS)-alpha
methyl-4-tetrazolylphenylglycine (MTPG) or the adenosine receptor antagonist 8
phenyltheophylline. Furthermore, a strong synergistic effect was observed when
the striatal membranes were exposed to both CGS 21680 and 1S-3R-ACPD. In
agreement with the biochemical results, in unilaterally 6-OH-dopamine lesioned
rats 1S-3R-ACPD counteracted the turning behaviour induced by the D2 receptor
agonist quinpirole, but not by the D1 receptor agonist SKF 38393, and it
synergistically potentiated the antagonistic effect of CGS 21680 on quinpirole
induced turning behaviour.
PMID- 10193905
TI - Antagonistic properties of the suramin analogue NF023 at heterologously expressed
P2X receptors.
AB - The suramin analogue 8,8'-(carbonylbis(imino-3,1-phenylene
carbonylimino)bis(1,3,5-naphthalenetrisulfonic acid) (NF023) antagonizes in a
competitive fashion P2X receptor-mediated responses in certain vascular and
visceral smooth muscles. In the present study, the effect of NF023 on voltage
clamped Xenopus oocytes heterologously expressing homomultimeric P2X1-P2X4 as
well as heteromultimeric P2X2/P2X3 receptors has been characterized. P2X1
receptors were most sensitive to inhibition by NF023 with IC50 values of 0.24 and
0.21 microM for the rat and human homologue, respectively. P2X3 receptors have an
intermediate sensitivity with IC50 values of 8.5 and 28.9 microM for rat and
human subtypes, respectively and P2X2 was the least sensitive subtype (IC50 > 50
microM). P2X4 receptors were insensitive to NF023 at concentrations up to 100
microM. Coexpression of rat P2X3 with rat P2X2 resulted in receptors whose
sensitivity to NF023 was identical to that obtained for homomultimeric rat P2X3
receptors (alphabeta meATP as agonist; IC50 = 1.4 and 1.6 microM, respectively).
NF023 inhibited P2X1 receptors in a voltage-insensitive manner. In addition,
NF023 (5 and 30 microM) caused a shift of the concentration-response curve to the
right without affecting the maximal response to ATP (K(B) = 1.1 +/- 0.2 microM).
Our results indicate that NF023 is a subtype-selective and surmountable
antagonist at P2X1 receptors heterologously expressed in Xenopus oocytes.
PMID- 10193906
TI - Effects of local application of 5-hydroxytryptamine into the dorsal or median
raphe nuclei on haloperidol-induced catalepsy in the rat.
AB - The effects of local application of the endogenous brain neurotransmitter 5
hydroxytryptamine (5-HT; serotonin) into the dorsal (DR) or median (MR) raphe
nuclei on haloperidol-induced catalepsy (CAT) in rats were studied. Local
application of 5-HT (40 microg, -10 min) into the DR or MR, respectively,
produced a significant reversal of haloperidol-induced CAT. Lower doses (5 or 25
microg) of 5-HT were ineffective. Compared to previous studies using the
selective 5-HT1A receptor agonist 8-OH-DPAT, the non-selective endogenous
serotonin receptor agonist 5-HT was significantly less potent in this paradigm.
Furthermore, the observed anticataleptic effect of 5-HT was seen following
injections into both DR or MR nuclei. The reversal of CAT by local application of
5-HT (40 microg) into the DR was significant also at 70 min after 5-HT
administration, with the same tendency for 5-HT injections into the MR. At this
time interval, other serotonergic behavioral symptoms like head twitches and wet
dog shakes also emerged. The early reversal of CAT by local 5-HT administration
into the MR is in all probability mediated via stimulation of 5-HT1A
autoreceptors on raphe serotonergic cell bodies. The reversal of CAT following 5
HT injections into the DR might alternatively be mediated via functional
mechanisms other than stimulation of 5-HT1A autoreceptors. The anticataleptic
effects observed at the later observation time could be due to stimulation of
postsynaptic 5-HT2 receptors following diffusion of 5-HT into 5-HT2 receptor rich
areas of the brain.
PMID- 10193907
TI - Amphetamine reverses or blocks the operation of the human noradrenaline
transporter depending on its concentration: superfusion studies on transfected
cells.
AB - Whether amphetamine enhances noradrenergic activity by uptake blockade or a
releasing action is still a matter of debate. In order to gain insight into the
interaction of amphetamine with the noradrenaline transporter its cDNA was
transfected into COS-7 cells (NAT-cells) or cotransfected with the cDNA of the
vesicular monoamine transporter (NAT/VMAT-cells); cells were loaded with
[3H]noradrenaline, superfused and the efflux analysed for total tritium and
[3H]noradrenaline. In NAT-cells amphetamine stimulated [3H]noradrenaline efflux
concentration-dependently when added to the superfusion buffer at 0.01, 0.1 and 1
microM. By contrast, 10 or 100 microM amphetamine stimulated efflux to a smaller
extent or not at all; however, on switching back to amphetamine-free buffer a
prompt increase of efflux was observed. Cocaine did not increase efflux per se
and blocked the amphetamine-induced efflux. In NAT/VMAT-cells amphetamine
stimulated efflux in a concentration-dependent manner. The effect showed
saturation at 1 microM and was not suppressed at higher concentrations. Cocaine
also elicited efflux from NAT/VMAT-cells concentration-dependently; the maximum
was reached at approximately 1 microM and amounted to only about half of the
amphetamine-induced efflux. It is concluded that amphetamine can induce
noradrenaline transporter mediated release only at high nanomolar to low
micromolar concentrations. At higher concentrations it blocks the noradrenaline
transporter; in this case, the releasing action of amphetamine, like that of
cocaine, is dependent on a vesicular pool of noradrenaline.
PMID- 10193908
TI - The role of VIP/PACAP receptor subtypes in spinal somatosensory processing in
rats with an experimental peripheral mononeuropathy.
AB - Peripheral nerve damage often results in the development of chronic pain states,
resistant to classical analgesics. Since vasoactive intestinal polypeptide (VIP)
and pituitary adenylate cyclase-activating polypeptide (PACAP) are up-regulated
in dorsal root ganglion cells following peripheral nerve injury, we investigated
the expression and influence of VPAC1, VPAC2 and PAC1 receptors in rat spinal
dorsal horn following a chronic constriction injury (CCI). Electrophysiological
studies revealed that selective antagonists of VPAC1, VPAC2 and PAC1 receptors
inhibit mustard oil-, but not brush-induced activity of dorsal horn neurones in
CCI animals, while cold-induced neuronal activity was attenuated by VPAC1 and
PAC1, but not VPAC2 receptor antagonists. Ionophoresis of selective agonists for
the receptor subtypes revealed that the VPAC2 receptor agonist excited twice as
many cells in CCI compared to normal animals, while the number of cells excited
by the VPAC1 receptor agonist decreased and responses to PACAP-38 remained
unchanged. In situ hybridisation histochemistry (ISHH) confirmed an increase in
the expression of VPAC2 receptor mRNA within the ipsilateral dorsal horn
following neuropathy, while VPAC1 receptor mRNA was seen to decrease and that for
PAC1 receptors remained unchanged. These data indicate that VIP/PACAP receptors
may be important regulatory factors in neuropathic pain states.
PMID- 10193909
TI - A comparative study in rats of the in vitro and in vivo pharmacology of the
acetylcholinesterase inhibitors tacrine, donepezil and NXX-066.
AB - The in vitro and in vivo effects of the novel acetylcholinesterase inhibitors
donepezil and NXX-066 have been compared to tacrine. Using purified
acetylcholinesterase from electric eel both tacrine and donepezil were shown to
be reversible mixed type inhibitors, binding to a similar site on the enzyme. In
contrast, NXX-066 was an irreversible non-competitive inhibitor. All three
compounds were potent inhibitors of rat brain acetylcholinesterase (IC50 [nM];
tacrine: 125 +/- 23; NXX-066: 148 +/- 15; donepezil: 33 +/- 12). Tacrine was also
a potent butyrylcholinesterase inhibitor. Donepezil and tacrine displaced
[3H]pirenzepine binding in rat brain homogenates (IC50 values [microM]; tacrine:
0.7; donepezil: 0.5) but NXX-066 was around 80 times less potent at this M1
muscarinic site. Studies of carbachol stimulated increases in [Ca2+]i in
neuroblastoma cells demonstrated that both donepezil and tacrine were M1
antagonists. Ligand binding suggested little activity of likely pharmacological
significance with any of the drugs at other neurotransmitter sites.
Intraperitoneal administration of the compounds to rats produced dose dependent
increases in salivation and tremor (ED50 [micromol/kg]; tacrine: 15, NXX-066: 35,
donepezil: 6) with NXX-066 having the most sustained effect on tremor. Following
oral administration, NXX-066 had the slowest onset but the greatest duration of
action. The relative potency also changed, tacrine having low potency (ED50
[micromol/kg]; tacrine: 200, NXX-066: 30, donepezil: 50). Salivation was severe
only in tacrine treated animals. Using in vivo microdialysis in cerebral cortex,
both NXX-066 and tacrine were found to produce a marked (at least 30-fold)
increase in extracellular acetylcholine which remained elevated for more than 2 h
after tacrine and 4 h after NXX-066.
PMID- 10193910
TI - Enhanced spontaneous transmitter release at murine motor nerve terminals with
cyclosporine.
AB - Cyclosporine, a calcineurin inhibitor, significantly enhances spontaneous
acetylcholine release after a brief tetanus and potentiates the effect of phorbol
12,13-dibutyrate. Both actions are prevented by the protein kinase C inhibitor,
bisindolylmaleimide iodide. Protein kinase C and calcineurin thus play important
roles in the balance between phosphorylation and dephosphorylation regulating
spontaneous transmitter release at motor nerve terminals.
PMID- 10193911
TI - Modern disorders of vitality: the struggle for legitimate incapacity.
PMID- 10193912
TI - Accelerated risk of hypertensive blood pressure recordings among Alzheimer
caregivers.
AB - The purpose of this study was to determine whether the stress of caregiving for
the Alzheimer's disease (AD) patient accelerates the likelihood of exceeding
hypertensive blood pressure (BP) criteria in periodic longitudinal home
assessments. In this cohort study, participants consisted of spousal caregivers
of AD patients (n = 144) and demographically equivalent non-caregiving controls
(n = 47). Thirty percent of caregivers and 33% of controls were receiving
antihypertensive treatment at study entry. Supine systolic and diastolic blood
pressure (SBP and DBP) was assessed by semi-automated recordings taken in the
home every 6 months for 2 to 6 years. Survival analyses (Cox proportional hazards
models) were used to determine whether the hazard for developing hypertension
(DBP>140, SBP>90) was greater in caregivers than in controls, and whether
increased hazards were related to background characteristics or the extent of
caregiving demands. Based on periodic 6-month assessments of BP over 6 years, the
hazards of meeting criteria for borderline hypertension were greater for
caregivers than for controls (Cox Proportional Hazards, chi2 [1, N = 174] = 4.86,
p = 0.03). This difference remained statistically significant (p<0.05) after
controlling for age, gender, education, socioeconomic status, body mass index,
and use of antihypertensive medications. Increased risk of hypertension was not
related to the extent of daily living assistance provided, patient problem
behaviors, or caregiver distress. The chronic stress of caring for an AD spouse
may have adverse effects on blood pressure; however, the mechanism for this
relationship remains unclear.
PMID- 10193913
TI - Changes in daily hassles and life events and the relationship with coronary heart
disease risk factors: a 2-year longitudinal study in 27-29-year-old males and
females.
AB - To investigate the relationship between changes in daily hassles and life events
and biological (lipoproteins, blood pressure, body fat, and body fat
distribution) and lifestyle (physical activity, smoking and alcohol consumption)
risk factors for coronary heart disease (CHD) 166 subjects were measured twice,
at 27 and 29 years of age. The results showed that changes in daily hassles were
positively related to changes in lipoprotein levels, daily physical activity, and
to smoking behavior. These relationships were more pronounced for subjects with a
"rigid" coping style and subjects with type A behavior. Changes in life events
were also positively related to lipoprotein levels, but only for subjects with a
"rigid" coping style and only when the subjective appraisal of life events was
taken into account. It was concluded that the relationships seemed to be mediated
by different coping styles and type A behavior, that daily hassles were more
important in these relationships than life events, and that the relationships
with biological CHD risk factors were not influenced by lifestyle.
PMID- 10193914
TI - Psychological distress among cancer patients and informed consent.
AB - This study examines the relationships between satisfaction with information
provided, understanding of consent procedures, and levels of anxiety/depression
in a sample of patients undergoing radiotherapy for cancer. One hundred patients
completed a 13-item self-report questionnaire and the Hospital Anxiety and
Depression Scale (HADS). Twenty-two percent of patients could not recall signing
a consent form and, for those who did recall, the level of understanding for what
they had consented to was patchy. One fourth of patients could not recall being
told of the side-effects from radiotherapy and were unable to list even common
side-effects, such as tiredness, skin irritation, and sickness. No patient had
been told about the low risk of second malignancy. Twenty-eight percent of
patients were unhappy with the amount of information offered to them. Thirty
percent of patients reached caseness for adjustment disorder +/-
anxiety/depression. Thirteen percent of patients reached caseness for major
depression. There was a significant correlation between patients who scored
highly on the HADS and dissatisfaction with the information provided. Clinical
implications and possible mechanisms of these findings are discussed.
PMID- 10193915
TI - Changes in quality of life following unilateral pallidal stimulation in
Parkinson's disease.
AB - Twenty patients with Parkinson's disease (age range 38-70 years) completed the
Sickness Impact Profile (SIP) 2 months before and 3 months after long-term high
frequency electrostimulation of the globus pallidus internus to improve clinical
symptoms. The SIP provides an estimate of perceived quality of life on 12 health
status categories. Neurological assessment with the Hoehn and Yahr scale and the
Unified Parkinson's Disease Rating Scale revealed a significant postoperative
reduction in clinical symptomatology (p<0.001). The patients experienced a
general improvement in self-reported quality of life that exceeded the purely
motor and physical aspects of quality of life. The significant postoperative drop
in perceived impairment of communication skills can be considered the most
important subjective improvement. Longitudinal research on a larger sample of
patients is necessary to evaluate the durability of the subjective improvement in
quality of life after unilateral pallidal stimulation.
PMID- 10193916
TI - Anxiety, optimism and symptom reporting following surgery for acoustic neuroma.
AB - In this study, a sample of 141 patients operated on for acoustic neuroma tumor
were followed-up. The patients completed questionnaires on residual symptoms,
hearing problems, anxiety, and optimism. Postoperative facial function was
assessed by the treating physician. Multiple regression analyses showed that
anxiety, age, and facial function were associated with symptom reporting. Anxiety
was also related to hearing problems. Optimism was not associated with either
symptoms or hearing problems. Results on the Beck Anxiety Inventory showed that
relatively few patients had a moderate degree of anxiety.
PMID- 10193917
TI - Screening for somatization and hypochondriasis in primary care and neurological
in-patients: a seven-item scale for hypochondriasis and somatization.
AB - The aim of this study was to investigate the internal and external validity of
the Whiteley Index as a screening instrument for somatization illness. A 14-item
version of the Whiteley Index for hypochondriacal traits was given to 99 of 191
consecutive primary care patients, aged 18-65 years, and to 100 consecutive
patients, aged 18-60 years, admitted for the first time to a neurological ward.
The primary care sample was, in addition, interviewed by means of the SCAN
(Schedules for Clinical Assessment in Neuropsychiatry) psychiatric interview. The
GPs and the neurologists were asked to rate various characteristics of the
patients that might indicate somatization. The internal validity of the Whiteley
Index was tested by means of latent structure analysis. On this basis, a reduced
seven-item scale (Whiteley-7 scale) and two subscales (i.e., an Illness
Conviction and Illness Worrying scale, each with three items) were constructed.
All three had a high internal validity fitting into the very restricted Rasch
statistical model (p>0.05) and an acceptable transferability between most of the
subpopulations investigated. In the primary care population, the Whiteley-7 and
the Illness Conviction scales at cut-point 0/1 showed 1.00 and 0.87 sensitivity
and 0.65 and 0.87 specificity, respectively, using as "gold standard" the
fulfillment of criteria for at least one ICD-10 somatoform disorder, and 0.71 and
0.63 sensitivity and 0.62 and 0.87 specificity, respectively, as gold standard
for the fulfillment of criteria for at least one DSM-IV somatoform disorder,
excluding the NOS diagnostic group. The Illness Worrying subscale showed less
impressive performance in this respect. The agreement between the Whiteley-7
scale including the two subscales and neurologists' rating and the GPs' rating
and the somatization subscale on the SCL-90 was modest or worse. It may be
concluded that the Whiteley-7 scale and the Illness Conviction subscale had
acceptable psychometric profiles, and both seem to be promising screening tools
for not only hypochondriasis but also for somatoform disorders in general.
PMID- 10193918
TI - Body image in obese patients before and after stable weight reduction following
bariatric surgery.
AB - The role of possessing an abnormal body weight in the body image alterations of
obese patients was evaluated in bariatric surgery subjects prior to and at long
term after operation, when body weight and shape had become steadily normalized.
Body image was assessed by the body dissatisfaction scale of the Eating Disorders
Inventory, the Body Shape Questionnaire, and the Body Attitude Questionnaire.
When the individuals were obese, a sharply impaired body image was observed;
following operation, weight loss corresponded to normalization of body
dissatisfaction, feeling of fatness, and physical attractiveness, whereas body
disparagement and salience of shape, although improved in comparison to
preoperative data, remained significantly different from that of controls. In the
obese patients, some aspects of body image alterations are substantially
accounted for by overweight status; other aspects reflect inner feelings, which
are partially independent of the actual body weight and shape.
PMID- 10193919
TI - State and trait anxiety in women affected by allergic and vasomotor rhinitis.
AB - It is still debatable whether anxiety and depression in patients affected by
rhinitis could play a role in the genesis of the disease, whether they are a
consequence of the symptoms. The aim of this study was to evaluate anxiety levels
in both state and trait forms, and depression, in patients affected by allergic
(AR) and vasomotor rhinitis (VMR). A total of 45 women, 24 AR and 21 VMR were
compared with 64 healthy nonallergic women matched for age and sociodemographic
characteristics. All subjects were administered the State and Trait Anxiety
Inventory (STAI) and the Zung self-rating depression scale. The percentage of
subjects with high levels of state anxiety was significantly higher in AR
(p<0.005) and VMR (p<0.01) with respect to controls. The percentage of subjects
with high levels of trait anxiety was significantly higher in AR (p<0.001) and
VMR (p<0.05) than controls. There was no significant difference in depression
between AR and VMR and controls. No significant difference was found in state
anxiety, trait anxiety, or depression between AR and VMR. In conclusion, anxiety
in patients with rhinitis is present both as a state and as a trait, at least
when measured with the STAI.
PMID- 10193920
TI - Dissociative experiences and psychopathology in conversion disorders.
AB - The concepts of dissociation and conversion are historically linked with the
first psychodynamic ideas on hysteria. However, the abolition of "hysterical
neurosis" from current nosology has led to independent developments of these
theoretical models. Recent studies found a high degree of somatization in
dissociative disorders. However, little is known about dissociation in conversion
disorders. We assessed 72 patients with conversion disorders for their
dissociative and general psychopathology using the German version of the
Dissociative Experience Scale (DES) and the Symptom Check List (SCL-90-R). They
were compared with a control group of 96 psychiatric patients suffering from
various neurotic disorders, who were matched for gender and age. Dissociative
symptoms were significantly more frequent in conversion disorder patients than in
controls. There were no differences in the SCL-90-R scores between the two
groups. Our findings support the theory of similar psychological processes
underlying conversion and dissociative disorders despite their descriptive
differences.
PMID- 10193921
TI - A test of the structural model of initiation of dieting among adolescent girls.
AB - This article reports alternative findings from a pilot study to those presented
recently (Strong GF, Huon KG. J. Psychosom. Res., 1998; 44:315-326) in regard to
the proposed model of sociopsychological processes involved in the initiation of
dieting among young adolescent girls. One hundred thirteen female high school
pupils completed a battery of questionnaires that assessed dieting status,
dietary restraint, autonomous functioning, skill-related functioning, social
influence, and family functioning. The results indicate that family functioning
predicts dietary restraint but that this effect is mediated by peer influence to
diet. Furthermore, family functioning was associated with autonomous functioning,
suggesting that this relationship should be pursued in a future test of the
model. This pattern of results is different from an earlier test of the model,
which indicated only a parental influence on dieting status. The results confirm
that peer influences should be retained as a causal factor in a reformulated
structural model.
PMID- 10193922
TI - Morphological maturation of left ventricle in fetal rats: changes in left
ventricular volume, mass, wall thickness, and mitral valvular size.
AB - Morphological changes in the left ventricles of fetal rats from 17 to 21 days of
gestation were studied using the rapid whole-body freezing technique. Wistar rats
(pregnant period, 21.5 days) were used. Left ventricular volume, mass, wall
thickness, and area of mitral valvular orifice increased rapidly and linearly
during the observation period. The ratio of the mass to volume of the left
ventricle gradually decreased as the fetuses grew older, and by 21st day of
gestation it was 52% that of 17 days of gestation. The ratio of the area of
mitral valvular orifice to left ventricular volume also decreased by 29% during
the same period. Thus we see that the left ventricle of fetal rat was in the
condition of physiological hypertrophy and had the large mitral valvular orifice
in early gestational age. We suggest that the decrease of the ratio of mass to
volume of the left ventricle with the progression of gestational age indicates
the morphological maturation of the left ventricle to adapt to the rapid increase
of volume overload during the perinatal period.
PMID- 10193923
TI - Crying, fussing and colic behaviour in breast- and bottle-fed infants.
AB - Persistent infant crying and "colic" have been linked in some studies to feeding,
but this association has not been tested in a planned longitudinal study
comparing breast- with formula fed babies. We used validated maternal diaries of
infant behaviours, kept for three days at both two and six weeks of infant age,
in a comparative study of 97 breast- or formula fed babies. The total duration of
overall crying rose significantly between 2 and 6 weeks in breast-fed infants and
fell in those fed formula. At 6 weeks, breast-fed infants cried an average of
almost 40 minutes more per day than formula fed infants; and 31% cried for more
than three hours per day, compared with only 12% of the formula fed group. At six
weeks, breast-fed infants also slept almost 80 minutes less per day than the
formula fed babies. While six weeks is the established peak age for infant
crying, those fed formula peaked much earlier and at 2 weeks intense crying/colic
behaviour occurred in 43% of formula fed babies and just 16% of those fed by
breast. These findings link the timing of the infant crying peak to the mode of
feeding. Our data indicate that any regimen designed to reduce crying should
commence in the neonatal period in formula fed infants.
PMID- 10193924
TI - The 'pharmacology' of neuronal rescue with cerebral hypothermia.
AB - The neuroprotective effects of hypothermia during cerebral ischaemia or asphyxia
are well known. Although, in view of this, the possibility of a therapeutic role
for hypothermia during or after resuscitation from such insults has been a long
standing focus of research, early studies had limited and contradictory results.
Clinically and experimentally severe perinatal asphyxial injury is associated
with a latent phase after reperfusion, with initial recovery of cerebral energy
metabolism but EEG suppression, followed by a secondary phase with seizures,
cytotoxic edema, accumulation of cytotoxins, and cerebral energy failure from 6
to 15 h after birth. Recent studies have led to the hypothesis that changes in
post-ischaemic cerebral temperature can critically modulate encephalopathic
processes which are initiated during the primary phase of hypoxia-ischaemia, but
which extend into the secondary phase of cerebral injury. This conceptual
framework allows a better understanding of the 'pharmacological' parameters that
determine effective hypothermic neuroprotection, including the timing of
initiation of cooling, its duration and the depth of cooling attained. Moderate
cerebral hypothermia initiated in the latent phase, between one and as late as 6
hours after reperfusion, and continued for a sufficient duration in relation to
the severity of the cerebral injury, has been associated with potent, long
lasting neuroprotection in both adult and perinatal species. These encouraging
results must be balanced against the adverse systemic effects of hypothermia.
Randomised clinical trials are in progress to establish the safety and efficacy
of prolonged cerebral hypothermia.
PMID- 10193925
TI - Development of baroreflex influences on heart rate variability in preterm
infants.
AB - To investigate developmental changes in autonomic cardiovascular reflexes in
preterm infants, we used autoregressive power spectral analysis to analyze the
effect of upright tilting on heart rate variability in preterm infants. Twenty
eight infants were studied in a longitudinal fashion beginning at 28-32 weeks
postconceptional age (postnatal age 1-5 weeks). Each week, heart rate variability
in the supine position and after 45 degrees head-up tilt was analyzed by spectral
analysis. With the initial study of each infant, there was no significant change
in heart rate following head-up tilt compared with baseline (-0.5+/-0.9 bpm).
However, linear regression analysis revealed that with increasing postnatal age,
the change in heart rate in response to tilting became more positive (mean slope
of regressions 0.45+/-0.12 bpm/week, P<0.005). The power spectral density of R-R
interval variability in the low-(LF; 0.02-0.15 Hz) and high-(HF; 0.15-1.5 Hz)
frequency ranges were obtained and the values normalized by dividing each
component by the total power. For measurements obtained in the supine position,
the LF/HF ratio progressively decreased with increasing postnatal age, indicating
a maturational change in sympathovagal balance. We used the difference in the
LF/HF ratio between tilt and the recumbent position as a measure of the change in
autonomic input to the heart in response to unloading of the arterial
baroreceptors. No significant change in these ratios were observed when infants
were first studied between 28 and 32 weeks postconceptional age, suggesting that
the cardiac baroreflex is poorly developed at this stage of development. However,
with postnatal maturation, the LF component of the power spectrum became
progressively larger with tilt relative to the basal state, such that the
difference between LF/HF(tilt) and LF/HF(base) became progressively more positive
(P <0.006). These findings suggest that in premature infants, cardiac
baroreceptor reflexes become more functional with postnatal development.
PMID- 10193926
TI - Increased amplitude modulation of continuous respiration precedes sudden infant
death syndrome -detection by spectral estimation of respirogram.
AB - The immaturity of the control of the autonomic nervous system has been suggested
as one of the key factors in the pathophysiology of sudden infant death syndrome
(SIDS). Therefore, the attenuated control of respiration may also cause more slow
oscillatory breathing among infants at risk of SIDS. In this study, patterns of
respiratory activity (RAV) and heart rate variability (HRV) were examined in
Medilog-records prospectively obtained from 22 tape recordings made on 16 babies
subsequently suffering from SIDS and from 22 matched control babies. A total of
248 signal segments, 120 s in duration, representing the state of regular
breathing were visually selected for further analysis. The digitised signal sets
were detrended, Fast-Fourier-transformed and autospectra as well as cross-spectra
for the HRV and HRV were computed. The RAV and HRV were examined at two spectral
bands: (1) a low frequency (LF) band 0.03-0.17 Hz (1.8-10 cycles/min) and (2) a
high frequency (HF) band 0.3-1.3 Hz (18-90 cycles/min). Different parameters of
each band were tested in the spectral analysis of cardiorespiratory control. The
LF/HF-ratio of the spectral peak area of the respiratory activity and the LF/HF
ratio of the spectral band area of the respiratory activity were greater in the
SIDS group when compared to the controls. No significant intergroup differences
were found in the parameters of HRV, or the cross-spectral parameters.
Interestingly, the technique appeared helpful in displaying that the victims of
SIDS had a significantly greater amount of slow oscillation in the continuous
respiratory signal (1.05+/-1.89 vs. 0.41+/-0.57, P=0.02). In the victims of SIDS
the respiratory control system seems to be less stable and cause more slow
oscillatory breathing and this can be detected using spectral analysis of
respiratory activity even during breathing that visually seems to be regular.
PMID- 10193927
TI - Developmental characteristics of vessel density in the human fetal and infant
brains.
AB - We demonstrated the developmental characteristics of vessel density in the human
brain, using an antibody against CD31, which specifically reacts with
endothelium. In the cerebral cortex and subcortical white matter, the vessel
density was low at 16-28 weeks of gestation (GW), and then increased after 36 GW.
In the deep white matter, the vessel density was high in the middle fetal period
(16-24 GW), and then transiently decreased at 28-36 GW, and increasing after 39
GW. In the putamen, the vessel density was high at 20-21 GW, remained high
throughout the fetal period, and then rapidly increased after birth. In the basis
pontis, the number of vessels increased after 28 GW, and after 32 GW was greater
than in the pontine tegmentum. These alterations in vessel density may correlate
with the pathogenesis of perinatal brain injury. Thus, the transient decrease of
vessel density in the deep white matter may predispose to periventricular
leukomalacia in cerebral hypoperfusion. Similarly, the well-developed vascularity
in the basis pontis may predispose its relatively immature neurons to neuron
necrosis produced by free radical injury.
PMID- 10193928
TI - Mortality from birth to adult life: a longitudinal study of twins.
AB - We have examined mortality from birth through adult life in a cohort of 2562
twins born in Birmingham, UK, between 1950 and 1954. Their birthweights and
obstetric details had been recorded as part of a longitudinal study of births in
Birmingham. There were a total of 151 perinatal deaths (perinatal mortality rate
= 116 per 1000 births) and 227 infant deaths (infant mortality rate = 94 per 1000
live births). 70 deaths occurred after the age of one year. In comparison with
national mortality rates in the UK, overall mortality in the twins was high
(standard mortality rate, SMR = 259, 95% CI 221-300). Mortality was highest in
the first year of life and, although it then declined progressively, it remained
significantly higher that that of the general population until age 5 years. The
excess mortality was largely due to conditions originating in the perinatal
period but there were excess rates of congenital abnormalities, diseases of the
respiratory system, digestive system and nervous and sensory organs. A Cox
proportional Hazards analysis showed that the risk of death was related to low
birthweight, prematurity and male sex. Death of the co-twin was highly predictive
of mortality throughout the period of follow up. These studies not only underline
the excess mortality associated with twin birth but show for the first time that
this excess mortality extends into childhood.
PMID- 10193929
TI - Mechanisms initiating lung injury in the preterm.
AB - Bronchopulmonary dysplasia (BPD)/chronic lung disease occurs primarily in very
low birth weight infants (VLBW) often without antecedent severe respiratory
distress syndrome. The BPD in these VLBW infants results in less fibrosis than
the traditional BPD but the normal process of alveolarization seems to be
disrupted. This review develops the thesis that BPD in VLBW infants results from
inflammatory mediators interfering with the signaling required for normal late
gestational lung development. Proinflammatory mediators may be elevated because
of fetal exposure, postnatal infection or by release from preterm lungs
ventilated at either low or high lung volumes. The preterm lung is highly
susceptible to injury during resuscitation or more chronic mechanical ventilation
because the gas volumes/kg body weight of the lungs are small. An understanding
of what causes cytokine release and how cytokines influence lung development is
necessary to develop targeted therapies to minimize BPD. However, care strategies
that minimize inflammation and ventilator-induced lung injury should help
decrease BPD.
PMID- 10193930
TI - Detection of premalignant oral lesions in hamsters with an endoscopic
fluorescence imaging system.
AB - BACKGROUND: Various methods of detecting cancer with fluorescence have been
developed. One type of fluorescence is based on the tumor-localizing properties
of certain dyes. However, the phototoxicity of most known tumor-localizing dyes
hinders the safe use of such diagnostic methods. The authors have developed a
fluorescence imaging system to detect the distribution of a nontoxic dye,
fluorescein, and they have evaluated the feasibility of the system by using it to
detect oral dysplastic lesions in hamsters. METHODS: Dysplasia was induced in the
cheek pouches of hamsters by application of the carcinogen 9,10-dimethyl-1,2
benzantracene. Fluorescein was administered to the hamsters either intravenously
or orally before the fluorescence examination. The endoscopic fluorescence system
produced dye-distribution images of both treated and control pouches. Two
fluorescence images in different spectral regions were processed for each dye
image. Biopsy material from both pouches was examined histopathologically.
RESULTS: The accumulation of fluorescein was detected in 22 of 23 specimens
containing dysplastic lesions. CONCLUSIONS: These results demonstrate the utility
of this fluorescein accumulation method in the detection of dysplasia. The
accumulation of fluorescein in dysplastic lesions may point to acidification of
interstitial medium in such lesions.
PMID- 10193931
TI - High rate of clinical complete response to weekly outpatient neoadjuvant
chemotherapy in oral carcinoma patients using a new regimen of cisplatin, 5
fluorouracil, and bleomycin alternating with methotrexate and epirubicin.
AB - BACKGROUND: A Phase II trial was initiated to evaluate the response to and
toxicity of a new regimen of weekly outpatient neoadjuvant chemotherapy in
patients with oral carcinoma. METHODS: Patients with previously untreated
squamous cell carcinoma of the oral cavity were eligible for this trial. The
neoadjuvant chemotherapy was comprised of cisplatin, 25 mg/m2, 5-fluorouracil,
1000 mg/m2, and bleomycin, 10 mg/m2, mixed in normal saline as a 24-hour
intravenous (i.v.) infusion, alternating with methotrexate, 30 mg/m2, and
epirubicin, 30 mg/m2, as an i.v. bolus (PFB/ME) on a weekly schedule for 8-12
weeks. In patients with American Joint Committee on Cancer Stage IV disease who
completed neoadjuvant chemotherapy, surgery was preferred to radiotherapy, unless
patients refused surgery. RESULTS: A total of 40 patients (82.5% with Stage IV
disease) with previously untreated oral carcinoma were enrolled. The median size
of the primary tumor was 7 cm (range, 3-13 cm). Fifty percent of patients had
tumor penetrating through the oral mucosa to the cheek skin and 62.5% had bony
destruction. Detectable cervical lymph nodes were noted in 77.5% of patients.
After neoadjuvant weekly chemotherapy, 22 patients (55%) showed complete response
(CR) and 15 patients (37.5%) showed partial response, for an overall response
rate of 92.5%. World Health Organization Grade 3/4 toxicity included mucositis
(7.5%), leukopenia (25%), anemia (10%), and thrombocytopenia (2.5%). Eleven of 33
patients with Stage IV disease underwent surgery, and pathologic CR (2 patients)
or microscopic residual tumor (4 patients) was noted (54.5%). CONCLUSIONS: The
results of the current study indicate that a weekly PFB/ME neoadjuvant
chemotherapy regimen is highly effective for the treatment of patients with oral
carcinoma. In addition, this regimen has low toxicity. The authors believe that
implementation of this regimen into a multimodality therapy protocol deserves
further study.
PMID- 10193932
TI - Staining of interleukin-10 predicts clinical outcome in patients with
nasopharyngeal carcinoma.
AB - BACKGROUND: Interleukin-10 (IL-10) has been implicated as an important modulator
of lymphoid cells, and its sequence is homologous to an open reading frame in the
Epstein-Barr virus (EBV) genome. Nasopharyngeal carcinoma (NPC) is a
representative tumor related to EBV infection. METHODS: The authors investigated
the expression of IL-10 in 21 primary NPCs by using an immunohistochemical
approach to examine its prognostic significance. RESULTS: IL-10 staining was
positive in 12 of 21 primary NPCs (57%). There was no association between IL-10
expression and gender, tumor size, the occurrence of lymph node metastases,
clinical stage, or recurrence. However, there was a significant difference in
overall survival between the negative expression and positive expression of IL-10
(P = 0.0348). Although 87.5% of the IL-10 negative group survived for 5 years,
only 15.6% of IL-10 positive patients survived for that length of time by the
Kaplan-Meier method. IL-10 expression was significant as an independent
prognostic indicator of overall survival by multivariate analysis using the Cox
proportional hazards model (odds ratio, 26.64; P = 0.0019). CONCLUSIONS: The
results imply that expression of IL-10 is a prognostic factor in patients with
NPC and may prove valuable in selecting patients with NPC who are candidates for
aggressive therapy.
PMID- 10193933
TI - The time course of histologic remission after treatment of patients with
nasopharyngeal carcinoma.
AB - BACKGROUND: The objective of this study was to define the time course of
histologic remission and to evaluate the prognostic significance of delayed
histologic remission of patients with nasopharyngeal carcinoma (NPC). METHODS:
Between 1986-1994, 803 patients underwent serial postradiotherapy nasopharyngeal
biopsies. Patients with positive histology underwent repeated biopsies every 2
weeks until the biopsies were found to be negative or, if remission did not occur
by the 12th week after radiotherapy, treatment was initiated for persistent
disease. Patients with positive histology found after the fifth week but who
achieved spontaneous remission before the twelfth week were considered to have
delayed histologic remission. Negative histology by the sixth week was considered
early histologic remission. The outcome of patients with delayed histologic
remission, early histologic remission, and persistent disease were compared.
RESULTS: Six hundred and seventeen patients (76.8%) had negative histology within
12 weeks of the completion of radiotherapy and 55 (6.9%) had persistent disease
at Week 12. In 131 patients (16.3%) spontaneous remission was observed in repeat
biopsies after initial positive histology. With increasing time after
radiotherapy, the incidence of positive histology decreased but more patients
were found to have persistent disease. Patients with early and delayed histologic
remission had 5-year NPC control rates of 82.4% and 76.8%, respectively (P =
0.35) versus a 40% NPC control rate among patients with persistent disease (P <
0.001). The 5-year survival rates were 75.3%, 79.4%, and 54.2%, respectively, for
the 3 groups (P < 0.001). CONCLUSIONS: A high proportion of early positive
histology remitted spontaneously. Delayed histologic remission in NPC patients is
not a poor prognostic factor and additional treatment is not necessary. A
confirmatory biopsy at 10 weeks is recommended before the initiation of salvage
treatment.
PMID- 10193934
TI - Effects of paclitaxel on the growth of normal, polyposis, and cancerous human
colonic epithelial cells.
AB - BACKGROUND: The specific paclitaxel dose or time course in the treatment of colon
carcinoma without the disruption of normal colonic cell proliferation is
currently not known. The aim of this study was to determine the effects of
paclitaxel on the growth of human colonic epithelial cells using cultures of
normal, polyposis, and cancerous cells. METHODS: Normal, polyposis, and cancerous
human colonic cells (Caco-2, T-84, and LoVo cell lines) were cultured, then
treated with paclitaxel (10(-9)-10(-5) M) for 0-7 days.[AU: Please verify all
dosages throughout.] Cell proliferation was assayed using either a Coulter
Counter or MTT-growth assay. Immunofluorescence and Western immunoblotting
measured P-glycoprotein. RESULTS: Low paclitaxel doses (1 x 10(-9)-10(-8) M) were
more effective than higher paclitaxel doses (>1 x 10(-8) M) in the growth
inhibition of polyposis, Caco-2, and LoVo cancer (but not T-84) cell lines. Low
paclitaxel doses had little effect on normal colonic cell growth over 7 days.
Higher paclitaxel doses (>1 x 10(-8)-10(-5) M) produced a dose-dependent
inhibitory effect on the growth of normal human colonic epithelial cells over 7
days but had no effect on the growth of polyposis, Caco-2, and LoVo cells over 3
7 days of treatment. Immunofluorescence and Western immunoblotting of cultures
showed that 1 x 10(-6) M paclitaxel increased P-glycoprotein expression in Caco-2
and LoVo cells. There was no effect of paclitaxel on P-glycoprotein expression in
T-84 cancer cells, which were found to have high endogenous basal levels of P
glycoprotein. P-glycoprotein expression in Caco-2 cells was found on plasma
membranes and in perinuclear areas. CONCLUSIONS: Lower paclitaxel doses are more
effective over time for the growth inhibition of polyposis and cancerous colonic
cells, with minimal effects on the growth of normal colonic epithelial cells.
Increased P-glycoprotein expression appears to be correlated with paclitaxel
resistance in polyposis and cancerous colonic cells.
PMID- 10193935
TI - Immunohistochemical detection of lymph node micrometastases from gallbladder
carcinoma using monoclonal anticytokeratin antibody.
AB - BACKGROUND: The objective of this study was to define the sensitivity and
clinical implications of the immunohistochemical detection of lymph node
micrometastases in patients with gallbladder carcinoma (GBC). METHODS: The
authors examined a total of 385 regional lymph nodes taken from 26 consecutive
patients with GBC who had undergone a radical resection. Histologic sections of
the primary tumor and regional lymph nodes in each case were stained with both
hematoxylin and eosin and an antibody against cytokeratins 8 and 18 (CAM5.2). A
"micrometastasis" was defined as a metastasis missed on routine histologic
examination with hematoxylin and eosin but detected by immunohistochemical
examination with CAM5.2. Survival rates were calculated only in patients with
Stage II or more advanced stage disease. RESULTS: All primary tumors were
positive for CAM5.2. Routine histologic examination revealed 53 positive lymph
nodes that were stained consistently with CAM5.2. Another seven lymph nodes had
micrometastases. Patients with micrometastases showed a significantly worse
survival rate than those without micrometastases (P = 0.037, log rank test).
Among patients with no lymph node disease on routine histologic examination,
there was a trend toward a worse survival rate in those with lymph node
micrometastases (P = 0.10, log rank test). The paraaortic lymph nodes were
involved more frequently in patients with lymph node micrometastases than those
without (P = 0.009, Fisher exact test). CONCLUSIONS: The immunohistochemical
detection of lymph node micrometastases using CAM5.2 is feasible in GBC patients
and is useful in predicting survival in patients undergoing radical resection.
Lymph node micrometastases may be an indicator of widespread lymph node disease
in patients with GBC.
PMID- 10193936
TI - Prospective study of the value of serum chromogranin A or serum gastrin levels in
the assessment of the presence, extent, or growth of gastrinomas.
AB - BACKGROUND: Serum chromogranin A levels (CgA) are reported by some authors to be
of clinical utility for assessing the presence or absence of a pancreatic
endocrine tumor and tumor extent or growth. The aim of the current study was to
assess this finding and compare the results with those from serum gastrin
determinations (FSG) in a large cohort of patients with gastrinomas. METHODS: In
112 consecutive patients with the Zollinger-Ellison syndrome serum CgA and FSG
levels were measured and correlated with disease activity, extent of disease, and
the presence of multiple endocrine neoplasia type-1 (MEN-1) or gastric carcinoid
tumors. RESULTS: Serum CgA levels drawn on 2 consecutive days correlated closely
(P < 0.00001) as did serum gastrin levels. Serum CgA levels correlated
significantly with FSG levels (P < 0.00001). Serum CgA and FSG levels were
significantly higher in patients with active disease than in disease free
patients (P < 0.00001). The sensitivity for the presence of disease was higher
for CgA compared with FSG (92% vs. 80%; P = 0.021). However, the specificity of
CgA was 67%. Serum CgA levels were not significantly different in the four
disease categories (stable extrahepatic disease, increasing extrahepatic disease,
stable liver metastases, and increasing liver metastases). FSG levels were
significantly lower in patients with stable extrahepatic disease compared with
those with increasing extrahepatic disease. However, both tumor markers decreased
significantly with a gastrinoma resection in five patients. The presence of MEN-1
or a gastric carcinoid tumor did not influence the results. CONCLUSIONS: The
results of the current study showed that serum CgA and FSG levels both are
sensitive tumor markers for the detection of a gastrinoma; however, CgA levels
have a relatively low specificity. Neither the magnitude of the serum CgA nor
gastrin level correlated with tumor growth or tumor extent and therefore cannot
be used to determine these variables. However, in contrast to some other studies,
the results of the current study show that changes in serum CgA or gastrin in a
given patient with time are related to the tumor extent and not to gastric
mucosal changes due to hypergastrinemia.
PMID- 10193937
TI - Neoadjuvant chemotherapy for patients with locally advanced gastric carcinoma:
effect on tumor cell microinvolvement of regional lymph nodes.
AB - BACKGROUND: In a previous study the authors demonstrated, using
immunohistochemical methods for epithelial antigens, that the regional lymph
nodes of gastric adenocarcinoma contained individual tumor cells or small
clusters of these cells (tumor cell microinvolvement [TCM]) in over 90% of cases.
In the current study the authors used the same method to investigate a series of
gastric adenocarcinoma cases treated with neoadjuvant chemotherapy prior to tumor
resection; their aim was to determine the effect of chemotherapy on TCM in
regional lymph nodes. METHODS: Resection specimens from 17 patients with
adenocarcinoma of the stomach, resected after neoadjuvant treatment and
classified by routine histology as ypN0, were included in this study. One section
from each of the 622 lymph nodes dissected from these specimens was stained by
immunohistochemical methods for cytokeratins and Ber-Ep4. RESULTS: Six patients
(35%) and 25 of the 622 lymph nodes (4.0%) had TCM, compared with 93% of patients
and 21.8% of lymph nodes in the previous study of patients treated with surgery
alone. The lymph node response to chemotherapy correlated with the pathologic
response of the primary tumor. Specifically, none of 5 patients with a complete
or major pathologic response versus 6 of 12 (50%) patients with minor, partial,
or no response had lymph node microinvolvement. CONCLUSIONS: In comparison to our
previous study, this study indicates that chemotherapy has a marked effect on
tumor cells in regional lymph nodes and that the extent of this effect can be
correlated with the degree of pathologic response of the primary tumor to
chemotherapy.
PMID- 10193938
TI - Risk factors for ovarian metastasis following curative resection of gastric
adenocarcinoma.
AB - BACKGROUND: Ovarian metastases from gastric carcinoma usually present as large,
symptomatic masses and sometimes represent the sole metastatic site. Accordingly,
prophylactic oophorectomy may be useful in the overall management of gastric
carcinoma. This retrospective study was undertaken to determine the risk factors
for ovarian metastasis following curative resection of gastric adenocarcinoma.
METHODS: The clinicopathologic profiles of 690 female patients who underwent
curative gastrectomy at Seoul National University Hospital between July 1987 and
June 1996 were reviewed, and their first relapse sites were identified. The
prognostic factors at the time of gastrectomy influencing ovarian metastasis were
analyzed using the Cox proportional hazards model. RESULTS: The overall 3-year
ovarian relapse rate was estimated to be 6.7% (95% confidence interval [CI], 4.2
9.2%). Multiple regression analysis indicated that the number of lymph nodes with
metastases and patient age were significant independent risk factors for ovarian
metastasis after curative resection of gastric adenocarcinoma. The number of
lymph nodes with metastases (>6) was associated with the highest risk of ovarian
metastasis, with an adjusted relative risk (aRR) of 38.0 (95% CI, 3.0-480.6). The
age of the patient (<50 years) also predicted the risk of ovarian metastasis,
with an aRR of 3.1 (95% CI, 1.4-7.0). Lauren diffuse type tended to predict for
ovarian metastasis with borderline significance (aRR, 5.9; 95% CI, 0.8-44.3). The
3-year ovarian relapse rate for patients younger than 50 years with more than 6
lymph nodes with metastases was estimated to be 39.5% (95% CI, 23.8-55.7%).
CONCLUSIONS: This study suggests that the risk of ovarian metastasis after
curative gastrectomy is strongly associated with the number of metastatic lymph
nodes (>6) and patient age (<50 years). Prospective studies are needed to
evaluate further the role of prophylactic oophorectomy in young female gastric
carcinoma patients who have multiple regional lymph nodes with metastases.
PMID- 10193939
TI - An early gastric carcinoma treatment strategy based on analysis of lymph node
metastasis.
AB - BACKGROUND: Newly developed therapies for early gastric carcinoma attempt to
consider patients' quality of life, but the applicability and effectiveness of
these treatments remain undetermined. METHODS: Clinicopathologic data of 612
consecutive patients with early gastric carcinoma, all of whom were treated by D1
and D2 gastrectomy, were analyzed. Patients with and without lymph node
metastases were compared in relation to age and gender distributions, surgical
procedures, histopathology of the tumors, 5-year prognosis, and in reference to
the preoperative and intraoperative assessments. RESULTS: The overall incidence
of lymph node metastases was 5.7%. Tumor depth and size were related to lymph
node metastases judged by univariate and multivariate analyses. Patients with
mucosal tumors showed no relation between metastatic rate and tumor size, whereas
those with submucosal tumors showed an increasing metastatic rate with tumor
size. In all cases but one, lymph node metastases were confined to lymph node
stations defined as Group 1 locations. Preoperative endoscopic ultrasonography
showed a 55% diagnostic accuracy in determining tumor depth and a 15% sensitivity
in diagnosing lymph node metastases. CONCLUSIONS: Patients with early gastric
carcinoma may be candidates for endoscopic mucosal resection if their tumor is
confined to the mucosa and measures < 1 cm in greatest dimension. Other limited
resections including D1 gastrectomy or standard D2 gastrectomy based on tumor
depth and size are appropriate. Based on the current study findings, the authors
propose a useful algorithm for managing such patients.
PMID- 10193940
TI - A pilot study of interleukin-2 for adult patients with acute myelogenous leukemia
in first complete remission.
AB - BACKGROUND: Interleukin-2 (IL-2) has immunomodulatory effects, including
stimulating the activity of cytotoxic T cells and natural killer cells, and
inducing the generation of lymphokine-activated killer cells. The authors
investigated whether IL-2 may improve the duration of complete remission (CR) and
survival in acute myelogenous leukemia (AML) patients in first CR. METHODS:
Eighteen patients were included after achieving a CR and receiving at least two
courses of consolidation chemotherapy. Therapy was comprised of IL-2 4.5 x 10(5)
U/m2 daily by continuous infusion (CI) for 12 weeks, plus boluses of 1 x 10(6)
U/m2 on Day 8 and weekly thereafter while continuing the CI. No further
chemotherapy was given after the administration of IL-2 was started. RESULTS: The
median age of the patients was 50 years (range, 18-73 years), and 7 patients
(39%) had an antecedent hematologic disorder (AHD). The median CR duration was 12
months, with 6 patients still alive in CR at a median follow-up of 64 months
(range, 50-82 months). Long term CR by cytogenetics occurred in 2 of 5 patients
with a normal karyotype (CR duration of 68+ months and 72+ months, respectively),
1 of 3 patients with t(8;21) (CR duration of 82+ months), 1 patient with inv(16)
(CR duration of 67+ months), none of 2 patients with -5/-7 (1 patient died in CR
after 10 months), 1 of 2 patients with abnormalities in chromosome 11 (CR
duration of 60+ months), and 1 of 4 patients with miscellaneous abnormalities (CR
duration of 74+ months). The median survival was 47 months. To assess the
significance of these results, the authors selected two historic controls
receiving long term postremission chemotherapy per each IL-2 case. The controls
had remained in CR for at least as long as the cases when the latter underwent
treatment initiation with IL-2 and were matched for the number of induction
courses required to achieve CR, AHD, cytogenetic abnormalities, and age. Six of
18 IL-2 patients (33%) were alive in CR at 3 years compared with 7 of 36 controls
(19%) (P = 0.31). Nine IL-2 patients (50%) were alive at 3 years compared with 10
controls (28%) (P = 0.13). CONCLUSIONS: These results suggest that IL-2 is
tolerable in AML patients in first CR and should be studied further in future
studies as a therapeutic strategy to prolong remission duration.
PMID- 10193941
TI - Altered expression of bcl-2 family member proteins in nonmelanoma skin cancer.
AB - BACKGROUND: Differentiation, proliferation, and cell death are coordinated
tightly within the epidermis. Alterations within keratinocytes that disrupt these
processes are believed to contribute to the development of nonmelanoma skin
cancers (NMSC). In the current study the authors examined the expression of
selected members of the bcl-2 gene family in the skin and in case-matched samples
of NMSC. METHODS: Immunohistochemistry was performed on tissue sections using
antibodies against bcl-2, bcl-x, bax, and bak. Case-matched frozen nonneoplastic
skin samples and tumor tissues were used for Western blot analysis. RESULTS: In
normal epidermis, bcl-2 oncoprotein is expressed in keratinocytes of the basal
layer but is down-regulated in suprabasal layers. The proapoptotic bax protein is
expressed at low levels in basal keratinocytes and is up-regulated in suprabasal
layers. The bcl-x and bak proteins both are expressed in the basal and spinous
strata but are down-regulated in the granular cell layer. Both bcl-2 and bax were
diffusely cytosolic whereas bcl-x and bak exhibited a distinct perinuclear
distribution. Squamous cell carcinomas (SCC) were negative for bcl-2 whereas bcl
2 increased 5.5-fold in basal cell carcinomas (BCC). The distribution of bcl-x
and bax proteins within BCC and SCC overlapped and were associated with squamous
differentiation. Bax protein was increased twofold to threefold in NMSC. An
increase in bak protein also was observed in SCC. However, bak was diffusely
cytosolic within BCC in contrast to the perinuclear distribution in nonneoplastic
keratinocytes. CONCLUSIONS: These findings suggest that altered expression of bcl
2 family members may play a role in the pathogenesis of NMSC.
PMID- 10193942
TI - Effects of tamoxifen on telomerase activity in breast carcinoma cell lines.
AB - BACKGROUND: The authors tested the effects of the antiestrogenic agent tamoxifen
on telomerase activity and cell proliferation in MCF-7 and MDA-MB-231 breast
carcinoma cell lines. MCF-7 cells belong to a known estrogen receptor positive
cell line, whereas MDA-MB-231 cells, previously thought to be estrogen receptor
negative, are now shown to contain estrogen receptor-beta. METHODS: Both cell
lines were grown in the presence of tamoxifen 10(-6), 10(-7), 10(-8), and 10(-9)
M for 10 days. Cells in separate flasks were harvested daily for determination of
total cell number, protein was extracted for determination of telomerase
activity, and RNA was extracted for reverse transcriptase-polymerase chain
reaction analysis to measure expression levels of the telomerase components (the
RNA component and the catalytic subunit) and estrogen receptors. RESULTS: Total
cell counts and telomerase activity levels of both cell lines with 10(-8) M
tamoxifen treatment were lower than control cells and other tamoxifen treatments.
Changes in the expression of individual telomerase components correlated with
telomerase activity. Estrogen receptor status did not correlate with telomerase
activity. CONCLUSIONS: Tamoxifen strongly affected both cell count and telomerase
activity within the 10(-8) M concentration of both cell lines. Cells were able to
overcome drug inhibition at all other doses after 4 days. Telomerase activity and
cell proliferation were correlated in both cell lines and depended on drug
concentration. Tamoxifen showed long term effects on cell proliferation of the
MCF-7 cells.
PMID- 10193943
TI - Axillary lymph node metastases associated with small invasive breast carcinomas.
AB - BACKGROUND: Over the past 20 years the proportion of invasive breast carcinomas
measuring < or = 1 cm has increased progressively. Information regarding the
effect of clinical and histologic characteristics on the frequency of lymph node
metastases associated with small invasive breast carcinomas is limited. METHODS:
A review of Surveillance, Epidemiology, and End Results data was performed using
cases diagnosed between January 1988 through December 1993. A total of 12,950
patients with invasive breast carcinomas measuring < or = 1 cm undergoing a
resection of the primary tumor and an axillary lymph node dissection were
included in this study. The effect of clinical and histologic characteristics on
the frequency of lymph node metastases was reviewed. RESULTS: The frequency of
lymph node metastases associated with T1a tumors was less than that observed from
T1b tumors (9.6% vs. 14.3%; P < 0.001). Tumors with favorable histology
(mucinous, papillary, and tubular carcinomas) had a lower frequency of lymph node
metastases compared with all other histologic types (3.9% vs. 13.9%; P < 0.001).
Increasing histologic grade was associated with an increased risk of lymph node
metastases ranging from 7.8% in Grade 1 tumors to 21.0% in Grade 4 tumors (P <
0.001). Increasing patient age was associated with a progressively decreasing
frequency of associated axillary lymph node metastases ranging from 22.6% in
women age < 40 years to 10.2% in women age > or = 70 years (P < 0.001).
CONCLUSIONS: Cases in which an axillary lymph node dissection can be avoided are
those with an associated frequency of lymph node metastases < or = 5%, including
T1a and T1b mucinous and tubular carcinomas, T1a papillary carcinomas, and T1a
Grade 1 carcinomas.
PMID- 10193944
TI - Preoperative prognostic variables and the impact of postoperative adjuvant
therapy on the outcomes of Stage IB or II cervical carcinoma patients with or
without pelvic lymph node metastases: an analysis of 891 cases.
AB - BACKGROUND: The purpose of this study was to investigate pretreatment variables
that could predict prognosis and to evaluate the impact of postoperative adjuvant
therapy on the outcomes of patients with Stage IB or II cervical carcinoma with
or without pelvic lymph node metastases. METHODS: Eight hundred ninety-one
patients with Stage IB or II cervical carcinoma who underwent radical
hysterectomy and bilateral pelvic lymphadenectomy as primary treatment at a
single institution were analyzed. Potential prognostic variables were studied.
RESULTS: Among the variables that could be assessed before treatment, depth of
cervical stromal invasion (determined by magnetic resonance imaging), clinical
stage, tumor size, grade of differentiation, and DNA index (determined by flow
cytometry) were independent predictors of outcome in multivariate analysis using
a Cox regression model. Three distinct prognostic groups (low, intermediate, and
high risk) were defined using these variables. Five-year recurrence free survival
(RFS) rates for the low, intermediate, and high risk groups were 94.6%, 82.7%,
and 62.3%, respectively (P = 0.0001), and overall survival (OS) rates were 98.4%,
84.5%, and 68.7%, respectively (P = 0.0001). Among patients with pelvic lymph
node metastases who were free of parametrial extension, those who received
postoperative chemotherapy or chemoradiotherapy had significantly better RFS (P =
0.017) and OS (P = 0.043) than those who received no adjuvant therapy. Among
patients without pelvic lymph node metastases but at high risk of recurrence,
those who received adjuvant radiotherapy had significantly better RFS (P = 0.015)
and marginally improved OS (P = 0.087) compared with those who received no
adjuvant therapy. CONCLUSIONS: A model containing assessable pretreatment
variables for predicting the prognoses of patients with early stage cervical
carcinoma was formulated. Subsets of patients for whom postoperative chemotherapy
or radiotherapy might be beneficial were identified. The data from this
retrospective review may be useful when future prospective trials of the
treatment of early stage cervical carcinoma are designed.
PMID- 10193945
TI - Incidence and distribution pattern of pelvic and paraaortic lymph node metastasis
in patients with Stages IB, IIA, and IIB cervical carcinoma treated with radical
hysterectomy.
AB - BACKGROUND: The incidence and distribution pattern of retroperitoneal lymph node
metastasis in patients with cervical carcinoma should be investigated based on
data from systematic pelvic lymph node (PLN) and paraaortic lymph node (PAN)
dissection, so that a basis can be established for determining the site of
selective lymph node dissection or sampling. METHODS: A total of 208 patients
with Stages IB, IIA, and IIB cervical carcinoma who underwent radical
hysterectomy and systematic pelvic and PAN dissection were investigated for lymph
node metastasis and histopathologic risk factors for lymph node metastasis.
RESULTS: Fifty-three patients (25.5%) had lymph node metastasis. The obturator
lymph nodes were most frequently involved, with a rate of 18.8% (39/208). Forty
nine of 53 node-positive patients had lymph node metastasis in the obturator,
internal iliac, or common iliac lymph nodes. Of 26 solitary lymph node metastases
confined to one node group, 18 were in the obturator, 3 in the internal iliac, 3
in the parametrial, and 2 in the common iliac lymph nodes. A multiple logistic
regression analysis revealed that deep cervical stromal invasion and lymph
vascular space invasion were related to PLN metastasis. It was also shown that
metastasis to bilateral PLNs (excluding the common iliac lymph nodes) as well as
metastasis to the common iliac lymph nodes were significantly related to PAN
metastasis. CONCLUSIONS: The results of this study suggest that the obturator
lymph nodes can be sentinel lymph nodes of cervical carcinoma. PAN metastasis
appears to occur secondarily to wide-spread PLN metastasis. These results provide
a basis for determining the site of selective lymph node dissection and for
estimating the existence of PAN metastasis from the pattern of metastasis in PLN
in patients with cervical carcinoma.
PMID- 10193946
TI - High dose chemotherapy with autologous stem cell support in the treatment of
patients with ovarian carcinoma: long term results for 105 patients.
AB - BACKGROUND: In this study, the authors reviewed long term results and prognostic
factors of high dose chemotherapy (HDC) with autologous stem cell support
administered to 105 patients with epithelial ovarian carcinoma. METHODS: Prior to
HDC, platinum-based chemotherapy was given to optimize (n = 94) and/or to
mobilize peripheral blood stem cells (n = 33). After maximum debulking surgery,
HDC with stem cell support was given; it consisted of cyclophosphamide,
doxoribicin, and cisplatin (Regimen A, administered to 58 patients) or
cyclophosphamide and carboplatin (Regimen B, administered to 47 patients).
RESULTS: Five-year overall and disease free survival (OS, DFS) rates (%)
according to stage were IC: 92.3, 92.3; II: 73.3, 73.3; III: 58.1, 35.7; IV:
33.7, 22.6; relapsed: 37.5, 31.0; OS, DFS at 8 years were IC: 92.3, 92.3; II:
73.3, 73.3; III: 48.8, 31.7; IV: 33.7, 22.6; relapsed: 37.5, 31.0. There was no
difference in survival between patients who received Regimens A and B despite an
increase in the total dose of platinum and an increase of more than 1.5- to 3.5
fold in the platinum course of HDC in Regimen B from the equivalence ratio of 4:1
between carboplatin and cisplatin. Among 65 Stage III and IV patients, the best
results were obtained for 35 patients with small volume disease: 5-year OS, DFS
rates were 74.3, 51.6, and 8-year OS, DFS rates were 66.4, 46.3. CONCLUSIONS:
Good long term results were obtained with HDC. Small volume residual disease,
platinum sensitivity, and histology excluding mucinous and clear cell
adenocarcinoma were important factors for better survival. However, because the
results were obtained for selected patients, a prospective, randomized study
comparing HDC and standard chemotherapy is necessary if any definitive
conclusions are to be drawn.
PMID- 10193947
TI - Squamous cell carcinoma of the penis and microscopic pathologic margins: how much
margin is needed for local cure?
AB - BACKGROUND: Total or partial penile amputation is an effective treatment for
invasive squamous cell carcinoma of the penis. The authors evaluated the relation
between paraffin section microscopic pathologic margins and local recurrence.
METHODS: Seventeen cases of biopsy proven squamous cell carcinoma of the penis
treated with partial or total penectomy were reviewed retrospectively. All
resections were performed by one surgeon (K.R.L.). Permanent microscopic
pathologic margins and pathologic classification were determined by one
pathologist (A.A.R.) using the American Joint Committee on Cancer TNM
classification of 1997. RESULTS: Seven of the 10 patients who underwent a partial
penectomy were followed for a mean duration of 33.1 months (range, 3-75 months).
The average microscopic pathologic margin was 14.4 mm (range, 0-40 mm) for
lesions classified as T1 or greater. Three patients had a microscopic margin < or
= 10 mm. There were no local or regional recurrences in this group of patients.
The 7 patients who underwent a total penectomy were followed for a mean duration
of 25.2 months (range, 5-76 months). There were no local recurrences and only one
inguinal recurrence. The average microscopic pathologic margin was 14.8 mm
(range, 0-50 mm) for all stages. There were 4 patients who had microscopic
pathologic margins < or = 10 mm, and all were free of local disease at the last
follow-up. CONCLUSIONS: None of the 14 patients followed developed local
recurrence. Also, no recurrence occurred in 7 patients who had microscopic
margins of < or =10 mm. This suggests that local control can be obtained with
margins measuring less than the standard 15-25 mm.
PMID- 10193948
TI - The prognostic significance of proliferation-associated nucleolar protein p120
expression in prostate adenocarcinoma: a comparison with cyclins A and B1, Ki-67,
proliferating cell nuclear antigen, and p34cdc2.
AB - BACKGROUND: In this study, the authors evaluated the prognostic significance of
the expression of nucleolar antigen p120, along with other cell proliferation
associated proteins, in prostate adenocarcinomas (PACs) and compared the results
with previously reported data on p34cdc2 cyclin-dependent kinase (p34 cdk).
METHODS: Archival sections from 132 PACs were immunostained with monoclonal
antibodies against p120, cyclin A, cyclin B1, Ki-67, and proliferating cell
nuclear antigen (PCNA). The DNA content of each tumor was determined by the
Feulgen method using image analysis. The immunohistochemistry (IHC) results were
correlated with tumor grade, stage, margin positivity, metastasis, ploidy, and
postsurgical disease recurrence. RESULTS: The overall positivity for the various
proteins follows: p120, 36%; cyclin A, 35%; cyclin B1, 43%; Ki-67, 46%; and PCNA,
32%. p120 correlated with grade (P = 0.004), stage (P = 0.01), ploidy (P = 0.02),
margin positivity (P = 0.03), and metastasis (P = 0.004). Cyclin B1 correlated
with ploidy (P = 0.04) and grade (P = 0.05), Ki-67 with grade (P = 0.02) and
margins (P = 0.03), and PCNA with grade (P = 0.01). Significant coexpression
among these proteins was noted, as was a significant association between the
expression of these markers and that previously reported for p34 cdk. In
univariate analysis, p120 (P = 0.01), cyclin A (P = 0.01) and p34 cdk (P = 0.002)
correlated with disease recurrence. In multivariate analysis of all these
proteins, only p34 cdk independently predicted postsurgical recurrence (P =
0.05). CONCLUSIONS: Nucleolar antigen p120 expression appears to be an additional
marker of aggressiveness in PACs. The significant coexpression of the various
cell cycle regulatory proteins support their collective role in tumor cell
proliferation, with p34 cdk positivity being an independent predictor of
postsurgical recurrence.
PMID- 10193949
TI - Transrectal ultrasound for staging prostate carcinoma prior to radiation therapy:
an evaluation based on disease outcome.
AB - BACKGROUND: Despite its subjectivity and inaccuracy, digital rectal examination
(DRE) has a long history of well-documented prognostic significance in patients
with prostate carcinoma. To the authors' knowledge, very few studies have
evaluated the relative prognostic merits of transrectal ultrasound (TRUS) versus
DRE. This question is addressed in this study. METHODS: The outcome for 558 men
with T1-T3, N0, M0 adenocarcinoma of the prostate who underwent both DRE and TRUS
and received external beam radiation without androgen ablation was evaluated
relative to the prognostic information from DRE, TRUS, or both. The outcome
endpoints were no evidence of disease (NED) (no relapse or rising prostate
specific antigen level) and freedom from metastases. Prognostic factors were
evaluated with univariate and multivariate techniques. The median follow-up was
55 months. RESULTS: Both purely DRE-based and purely TRUS-based T categories
correlated significantly with NED status. For DRE T categories, 6-year NED rates
for T1/T2 and T3 disease were 64% and 36%, respectively (P < 0.001). For TRUS T
categories, the rates for T1/T2 and T3 were 63% and 39%, respectively (P <
0.001). There were significant differences in patient composition between DRE and
TRUS T categories. Only 40% of patients were in the same DRE and TRUS category,
but the majority of the reclassification based on TRUS was within rather than
between major T categories (T1/T2 vs. T3). Changes between the prognostically
significant T1/T2 versus T3 categories occurred in < or =25%. This accounted for
the similarity in NED outcome for DRE and TRUS T categories. However, TRUS
categories did not discriminate significantly for metastatic recurrence between
T1/T2 and T3 categories, whereas DRE categories did. Upstaging or downstaging by
TRUS relative to DRE did not alter the DRE prognostic groupings substantially.
CONCLUSIONS: There was no clinically meaningful superiority of TRUS over DRE in
the definition of prognostically useful T categories. Moreover, the addition of
TRUS to DRE did not enhance the prognostic value of DRE findings in any
meaningful way. Despite its subjectivity and inaccuracy, DRE provides prognostic
information at least equivalent to TRUS and is preferable because of its low
cost.
PMID- 10193950
TI - Comparison of clinical staging algorithms and 111indium-capromab pendetide
immunoscintigraphy in the prediction of lymph node involvement in high risk
prostate carcinoma patients.
AB - BACKGROUND: The pretherapy prediction of occult lymph node involvement and the
avoidance of otherwise futile and potentially morbid definitive local therapy is
paramount in men with newly diagnosed prostate carcinoma. To identify patients
with prostate carcinoma who likely have lymph node involvement and would benefit
from staging lymphadenectomy prior to definitive local therapy, the authors
compared the ability of several predictive staging algorithms and a radiolabeled
monoclonal antibody scan to predict lymphatic metastases prior to treatment.
METHODS: Between August 1991 and June 1994, 198 men with clinical T2 or T3
classified (TNM) prostate carcinoma (bone scan negative) who were at high risk of
lymph node involvement underwent a 111In-capromab pendetide scan prior to staging
lymphadenectomy. Several predictive models based on preoperative prostate
specific antigen level, biopsy Gleason score, and clinical stage were selected to
predict those men having a > or =20% probability of lymph node involvement. The
ability to predict pathologic stage using several clinical algorithms and the
monoclonal antibody scan was compared with pathologic examination of the lymph
nodes. RESULTS: Overall, 39% of the pelvic lymph node specimens were positive for
metastatic disease by pathologic analysis. Published algorithms predicting lymph
node metastases had a positive predictive value (PPV) ranging from 40.5% to 46.6%
and an area under the receiver operating characteristic curve (AUC) ranging from
0.52 to 0.61. The monoclonal antibody scan had a PPV of 66.7% and an AUC of 0.71.
The differences between the PPV and the AUC for the individual clinical
algorithms when compared with immunoscintigraphy were statistically significant.
Combining the radiolabeled monoclonal antibody scan with clinical predictive
models, a PPV of up to 72.1% could be obtained. CONCLUSIONS: These data suggest
that the PPVs for the clinical predictive algorithms are similar and that the PPV
of the radiolabeled monoclonal antibody scan alone or in combination with the
algorithms has additional value in predicting lymph node involvement in prostate
carcinoma patients at high risk of regional disease spread. These algorithms and
the 111In-capromab pendetide scan may be used for the appropriate selection of
candidates for definitive local therapy in men with clinically localized prostate
carcinoma and significant risk of lymph node involvement.
PMID- 10193951
TI - Biologic behavior of and p53 overexpression in multifocal renal cell carcinoma of
clear cell type: an immunohistochemical study correlating grading, staging, and
proliferation markers.
AB - BACKGROUND: In the treatment of small renal cell carcinoma (RCC), there is
controversy between radical and nephron-sparing surgical treatment because of the
risk of tumor multifocality. The biologic behavior of multifocal RCC compared
with that of unifocal RCC is not well investigated, and the relevance of p53 and
the proliferation markers MIB-1 and proliferating cell nuclear antigen (PCNA) to
multifocal RCC is not yet established. METHODS: In this study, p53 protein
overexpression was investigated immunohistochemically in 27 multifocal and 65
unifocal clear cell RCCs using a monoclonal antibody (DO-1). The nuclear
expression of p53 was compared with the expression of PCNA and MIB-1 (Ki-67
antigen) and other prognostic factors, including grade and stage. RESULTS: Thirty
three RCCs (35.9%) had p53 positive nuclear staining. MIB-1 positivity was
significantly higher in p53 positive tumors than in p53 negative tumors. PCNA
positivity was not different in p53 positive tumors compared with p53 negative
tumors. Proliferation marker expression was not associated with tumor focality.
p53 overexpression was more often found in unifocal tumors than in multifocal
tumors. Intracellular accumulation of the p53 protein was related to tumor grade
but not to the T classification of tumor stage. In addition, lymph node
involvement was significantly associated with p53 overexpression in tumors of the
kidney. Focality did not influence progression free survival. CONCLUSIONS: This
study demonstrated that there is no difference in the proliferative activity or
biologic behavior of multifocal and unifocal tumors.
PMID- 10193952
TI - Front-line chemotherapy with cisplatin and etoposide for patients with brain
metastases from breast carcinoma, nonsmall cell lung carcinoma, or malignant
melanoma: a prospective study.
AB - BACKGROUND: The conventional treatment of brain metastases not amenable to
surgery is most often radiotherapy. Until now, pharmacologic issues related to
the blood brain barrier (BBB) prevented a wide evaluation of chemotherapy. The
authors previously reported that the combination of cisplatin (P) and etoposide
(E) had strikingly high activity in patients with brain metastases from breast
carcinoma. The purpose of this study was to assess, in a larger prospective
study, the front-line activity of that combination against brain metastases from
breast carcinoma (BC), nonsmall cell lung carcinoma (NSCLC), and malignant
melanoma (MM) in patients previously untreated with radiotherapy. METHODS: From
December 1986 to July 1993, 116 patients received P 100 mg/m2 on Day 1 and E 100
mg/m2 on Days 1, 3, and 5 or on Days 4, 6, and 8 every 3 weeks. An insignificant
change in the E schedule using the same dose on a random basis assured the
prospective enrollment and the registration of all cases. Six patients were not
eligible and three patients were excluded from the analysis because they were
lost to follow-up shortly after the date of registration. One-hundred seven
patients were considered for analysis. The distribution according to the primary
tumor site was BC in 56 patients (52%), NSCLC in 43 (40%), and MM in 8 (8%). The
first evaluation of response was performed after two cycles. In cases of no
disease progression, chemotherapy was continued to a maximum of six cycles.
RESULTS: Among the 56 patients with BC, 7 achieved complete response (CR) (13%),
14 achieved partial response (PR), 12 had no change (NC), 15 had progressive
disease (PD), and 8 had insufficient treatment or response was not assessed. The
CR plus rate was 38%. Among the 43 patients with NSCLC, 3 achieved CR (7%), 10
achieved PR, 15 had SD, 7 had PD, and 8 had insufficient treatment or response
was not assessed. The CR plus PR rate was 30%. None of the eight patients with MM
achieved an objective response. The median survival was 31 weeks for patients
with BC (range, 0-287), 32 for patients with NSCLC (0-392+), and 17 for patients
with MM (2-48). CONCLUSIONS: The combination of P and E is effective for patients
with brain metastases from BC and NSCLC. In this study, the response rate was of
the same order as that reported for disseminated disease without central nervous
system involvement. The survival figures compare favorably with some others
reported in the literature for patients given radiotherapy. A randomized study is
warranted to compare this chemotherapy followed by radiotherapy with radiotherapy
alone for patients with brain metastases from BC or NSCLC not amenable to surgery
or radiosurgery.
PMID- 10193953
TI - Central neurocytoma: histologic atypia, proliferation potential, and clinical
outcome.
AB - BACKGROUND: Although central neurocytomas are considered benign, recent reports
suggest that some patients with histologic atypia and/or elevated proliferation
potential may have a poor outcome. METHODS: A retrospective review identified 15
cases of central neurocytoma. Clinical follow-up was available for 14 patients.
Each tumor was evaluated for the presence of atypical histologic features,
including cellular pleomorphism, endothelial proliferation, and necrosis. The
proliferation potential was assessed by MIB-1 immunohistochemistry. The
correlation among histology, MIB-1 labeling index (MIB-1 LI), and clinical
outcome was evaluated. RESULTS: Histologic atypia was identified in 3 tumors
(20%). The MIB-1 LI ranged from 0.1% to 6.0%, and 5 cases (33%) had an MIB-1 LI
>2%. The correlation between histologic atypia and MIB-1 LI was poor, with only 1
tumor having both atypia and MIB-1 LI >2%. Clinical follow-up ranged from 13 to
255 months postoperatively (mean, 68 months). Although most patients were alive
and well at last follow-up, three developed symptomatic recurrence and one died
as a result of increased tumor growth. The tumors from all 4 patients with a poor
outcome had MIB-1 LI >2%, but only 1 had histologic atypia. CONCLUSIONS: The
proliferation potential of central neurocytoma is a useful predictor of clinical
outcome, whereas histologic atypia alone is not prognostically significant. It
would be appropriate to recognize a subgroup of central neurocytomas with
elevated proliferation potential as WHO Grade 2 lesions. The terms "atypical" and
"anaplastic" are not appropriate to describe these lesions, as they imply a
certain histologic appearance. The most accurate designation would be
"proliferating neurocytoma."
PMID- 10193954
TI - Human immunodeficiency virus negative Kaposi sarcoma and lymphoproliferative
disorders.
AB - BACKGROUND: The concomitant occurrence of more than one primary neoplasm in the
same individual has led researchers to seek possible common etiopathogenetic
factors. Kaposi sarcoma (KS) is a multicentric neoplasm of vascular origin and
perhaps viral etiology. Four forms of KS are known: classic or Mediterranean,
endemic or African, posttransplant, and epidemic or acquired immunodeficiency
syndrome-associated KS. In its classic form KS mainly affects elderly people and
often has a long and indolent course that occasionally allows other malignancies
to appear. Previous studies of the possible association between human
immunodeficiency virus (HIV) negative KS and lymphoproliferative disorders (LDs)
have produced discordant results. METHODS: To verify a possibly significant
association between HIV negative KS and LDs, data relating to 250 evaluable
Italian patients with HIV negative KS were evaluated retrospectively. RESULTS: Of
the 250 KS patients, only 6 (2.4%) were found to have had an LD: 2 with Hodgkin
lymphoma, 1 with non-Hodgkin lymphoma, 1 with cutaneous T-cell lymphoma, 1 with
acute promyelocytic leukemia, and 1 with B-chronic lymphocytic leukemia.
CONCLUSIONS: No significant association was found between HIV negative KS and LDs
in the patient population in the current study. The authors believe that age, LD,
or therapy-related immunodepression played a role in the cases in which KS
appeared after the LD by determining the passing to the lytic phase of the herpes
virus HHV8 already present in anatomic sites of latency/persistence.
PMID- 10193955
TI - Factors affecting the risk of contralateral Wilms tumor development: a report
from the National Wilms Tumor Study Group.
AB - BACKGROUND: Approximately 1% of children with unilateral Wilms tumor develop
contralateral disease. The authors assessed the demographic and histologic
features associated with metachronous bilateral Wilms tumor (BWT). METHODS:
Characteristics of all children registered on the first four National Wilms Tumor
Studies (NWTS) were recorded. The primary endpoint for evaluation was the first
appearance of Wilms tumor in the remaining kidney. The cumulative risk of
contralateral disease as a function of time since initial presentation was
calculated as 1 minus the Kaplan-Meier estimate of remaining free of
contralateral disease. A matched case control study was conducted to determine
whether the presence and type of nephrogenic rests (NRs) were associated with
metachronous BWT. RESULTS: Fifty-eight of 4669 registered children developed
metachronous BWT; 38 of 2445 females (expected, 30.2) versus 20 of 2224 males
(expected, 27.8) (P = 0.04) developed BWT. The cumulative incidence of
contralateral disease 6 years after initial diagnosis decreased from greater than
3% in the first NWTS to approximately 1.5% in the three subsequent studies (P =
0.08). Patients with NRs had a significantly increased risk of metachronous BWT.
This was particularly true for young children (20 of 206 age < 12 months compared
with 0 of 304 age > 12 months). Data from the matched case control study
confirmed the increased relative risk associated with young age and the presence
of NRs. CONCLUSIONS: Children younger than 12 months diagnosed with Wilms tumor
who also have NRs, in particular perilobar NRs, have a markedly increased risk of
developing contralateral disease and require frequent and regular surveillance
for several years. Surveillance is also recommended for those with NRs who are
diagnosed after the age of 12 months.
PMID- 10193956
TI - Primary follicular lymphoma of the testis in childhood.
AB - BACKGROUND: Follicular lymphoma in childhood is rare. The authors present four
unusual primary follicular lymphomas of the testis in children. METHODS: Tumor
tissue was evaluated using light microscopy, immunohistochemistry, flow
cytometry, and polymerase chain reaction (PCR) for immunoglobulin heavy chain
(IgH) and bcl-2 gene rearrangements. Southern blot and immunohistochemical
analyses were used to detect bcl-6 gene rearrangements and protein expression,
respectively. RESULTS: Four young boys ranging in age from 3 to 10 years were
diagnosed with Stage IE follicular large cell lymphoma (Grade 3). A B-cell
phenotype was documented in all four cases; monoclonality was confirmed in three
cases by demonstration of light chain restriction or clonal IgH gene
rearrangement. None of the lymphomas expressed Bcl-2 or p53 protein, and bcl-2
gene rearrangements were not found in the three lymphomas studied. In contrast,
Bcl-6 protein was expressed by all three lymphomas studied, and a bcl-6 gene
rearrangement was detected in the one case analyzed by Southern blot. All four
boys were treated by orchiectomy and combination chemotherapy and are alive with
no evidence of disease 18-44 months following their initial diagnoses.
CONCLUSIONS: Follicular lymphomas may rarely occur as primary testicular tumors
in prepubertal boys and, when localized, appear to be associated with a favorable
prognosis. In contrast to follicular lymphoma in adults, pediatric follicular
lymphomas of the testis are usually of large cell type (Grade 3) and lack bcl-2
or p53 abnormalities. The identification, in one case, of a bcl-6 gene
rearrangement suggests an alternate molecular pathogenesis for pediatric
follicular lymphoma.
PMID- 10193957
TI - Clonal change of infiltrating T-cells in children with familial hemophagocytic
lymphohistiocytosis: possible association with Epstein-Barr virus infection.
AB - BACKGROUND: Although familial hemophagocytic lymphohistiocytosis (FHL) has been
considered a T-cell disorder, to the authors' knowledge there are no previous
reports on the clonal basis of FHL. In the current study the authors analyzed the
clonality of T-cells in two FHL patients at the time of disease onset and at
disease progression. METHODS: Patient 1 had FHL and died of recurrent disease 4
months after bone marrow transplantation (BMT). His liver and spleen showed
massive infiltrations of CD3+, CD4-, and CD8+ T-cells. The Epstein-Barr virus
(EBV) genome was detected by in situ hybridization. Patient 2 also had FHL and
died of progressive disease 9 weeks after the onset of disease despite
chemotherapy. A polymerase chain reaction (PCR) analysis showed positive EBV
genome in the peripheral blood, liver, and spleen of Patient 2. In the two
patients, T-cell receptor-beta and alpha-chain variable region (TCR Vbeta and V
alpha) repertoires in peripheral mononuclear cells were analyzed at the time of
disease onset and at disease progression by the inverse PCR method. When a high
usage (> 15%) of a specific Vbeta family member was observed, a clonal analysis
was performed by PCR using beta-chain joining region (Jbeta) primers. The
clonality of specific Vbeta-Jbeta fragments was confirmed by a single strand
confirmation polymorphism (SSCP) analysis. RESULTS: Although there was no
preferential usage of Vbeta in Patient 1, the exclusive expression of Jbeta1.2
for Vbeta13 was observed. A high frequency of Vbeta13 also was observed at the
time of disease progression, but the Jbeta fragment for Vbeta13 was polyclonal.
In Patient 2, the restricted usage of Jbeta1.6 for Vbeta5a was observed at the
time of disease onset, whereas Jbeta1.1 and 1.2 for Vbeta4 were observed
exclusively at the time of disease progression. The clonality of Vbeta13-Jbeta1.2
in Patient 1 and Vbeta5a-Jbeta1.6 and Vbeta4-Jbeta1.1/Jbeta1.2 in Patient 2 was
confirmed by SSCP analysis. CONCLUSIONS: These findings suggest that the
polyclonal T-cell lymphoproliferative disease associated with EBV was induced
after BMT in Patient 1, and that the clonal change of expanded T-cells also was
induced by EBV in Patient 2. The clonal analysis of T-cells is a useful tool to
clarify the pathogenesis of FHL.
PMID- 10193958
TI - Comparison of four carbon dioxide resurfacing lasers. A clinical and
histopathologic evaluation.
AB - BACKGROUND: Several high-energy, pulsed and scanned carbon dioxide (CO2) lasers
are currently available for cutaneous resurfacing. Although each laser system
adheres to the same basic principles of selective photothermolysis, there are
significant differences between lasers with respect to tissue dwell time, energy
output, and laser beam profile. These differences may result in variable clinical
and histologic tissue effects. OBJECTIVE: The purpose of this study was to
examine the in vivo clinical and histopathologic effects of four different high
energy, pulsed or scanned CO2 resurfacing lasers. METHODS: A prospective study
using four different CO2 resurfacing lasers (Coherent UltraPulse, Tissue
Technologies TruPulse, Sharplan FeatherTouch, and Luxar NovaPulse) was performed.
The cheeks of seven patients were divided into four quadrants. Each quadrant was
randomly assigned to receive treatment with one of four CO2 lasers. Skin biopsies
were obtained intraoperatively from each quadrant, after each of three laser
passes, and at 1 and 3 months postoperatively. Blinded clinical assessments of
each laser quadrant were made at 1, 3, and 6 months postoperatively by three
physicians. Degree of lesional improvement as well as erythema severity, re
epithelialization rates, and presence of side effects were recorded. Blinded
histologic examination of laser-treated quadrants was performed to determine the
amount of tissue ablation, residual thermal damage, inflammation, and new
collagen synthesis. RESULTS: The four CO2 lasers produced equivalent clinical
improvement of rhytides and scars. Re-epithelialization occurred in all laser
quadrants by day 7. Postoperative erythema was most intense in the quadrants
treated by UltraPulse and NovaPulse; however, overall duration of erythema was
equivalent for all four laser systems (3 months). Postinflammatory
hyperpigmentation was the most frequently encountered side effect and occurred
with equal frequency in each quadrant. No scarring, hypopigmentation, or
infections were observed. After one laser pass, histologic examination revealed
partial ablation of the epidermis with the TruPulse laser and complete epidermal
ablation using the UltraPulse, NovaPulse, and FeatherTouch laser systems. The
greatest degree of residual thermal damage was seen after FeatherTouch and
NovaPulse laser irradiation. New collagen formation was greatest in the
UltraPulse and FeatherTouch laser-irradiated quadrants. CONCLUSIONS: Equivalent
clinical results were observed using the FeatherTouch, NovaPulse, TruPulse, and
UltraPulse CO2 lasers. While postoperative erythema intensity differed between
laser systems, total duration of erythema was equivalent. The four lasers under
study resulted in minimal residual thermal damage and stimulated new collagen
formation within 6 months after treatment.
PMID- 10193959
TI - Combined laser resurfacing with the 950-microsec pulsed CO2 + Er:YAG lasers.
AB - INTRODUCTION: Laser resurfacing with the 950 microsec pulsed CO2 laser has been
proven to be efficacious in improving photodamaged skin and acne scarring.
Unfortunately, prolonged erythema and delayed wound healing are common adverse
sequelae, which require intensive patient education and intervention. These
adverse effects may be due to the degree of nonspecific thermal damage present
after resurfacing with the CO2 laser. Since erbium: YAG (Er:YAG) laser
vaporization leaves far less thermal damage, it is hypothesized that its use
after CO2 laser resurfacing will decrease the extent of nonspecific damage and
result in improved wound healing. METHODS: Ten patients were randomized to
receive laser resurfacing of one-half of the face with the 950 Msec pulsed CO2
laser with 3 passes at 300 mJ, utilizing the computer pattern generator (CPG) at
settings of 596, 595, 584, and the other half of the face (randomly chosen)
resurfaced with the 950 Msec pulsed CO2 laser 2 passes with the CPG at 300 mJ at
settings of 596 and 595, followed by 2 passes with the Er:YAG laser (Derma-20 or
Derma-K, ESC Medical Systems, Inc., Needham, MA) with a 4 mm diameter spot size
at 1.7 J (approximately 14 J/cm2). Patients were evaluated in a "blinded" manner
clinically and histologically before resurfacing, immediately after resurfacing,
2 to 3 days postoperatively, 1 week postoperatively, and, 4 to 8 weeks
postoperatively. RESULTS: There was slightly less inflammation with the
CO2/Er:YAG-treated patients. The epidermis re-formed 1 to 2 days faster with
combination (UPCO2)/Er:YAG treatment than with UPCO2 laser treatment alone. In 7
of 10 patients, Er:YAG erythema resolved within 2-3 weeks with CO2 x 3 erythema
persisting at the 8-week follow-up period in all patients. Three of 10 patients
had no difference in the degree of erythema between the 2 treatment areas.
Clinical findings correlated with histologic findings of vascularity. There was
no difference in the extent or time of edema between techniques. The usual
demarcation line between cheek and neck at the mandibular angle was less apparent
when the UPCO2/Er:YAG combination was used. Two of 10 patients noted quicker
healing with the combination laser technique. CONCLUSION: Treating a patient with
the Er:YAG laser after treatment with the UPCO2 laser results in a decreased
incidence of adverse sequelae without a noticeable difference in the degree of
wrinkle improvement.
PMID- 10193960
TI - Laser resurfacing of the neck with the Erbium: YAG laser.
AB - BACKGROUND: Laser resurfacing of the face is widely used to correct the effects
of photoaging. The neck also develops a similar degree of photoaging, but is not
usually treated because a higher incidence of adverse effects can occur with
laser treatment. OBJECTIVE: To present a new method for treating photoaged skin
of the neck with an erbium:yttrium aluminum garnet (Er:YAG) laser. METHODS:
Twenty patients underwent Er:YAG laser resurfacing of the neck with one of two
methods. Method 1 consisted of using the Er:YAG with a 5-mm diameter collimated
beam at a fluence of 8.7 J/cm2 followed by a second pass using a 0.2 mm diameter
non-collimated spot at 1.7 J in a defocused mode with spot sizes ranging from
about 5 to 10 mm in diameter (fluences from 2-9 J/cm2). Method 2 consisted of
treating the entire neck with a single pass of the Er:YAG laser with a 4 mm
diameter non-collimated spot at 1.7 J (fluence of 13.5 J/cm2). A second pass at
identical settings was made on the upper half of the neck with a more defocused
pass using a 6-10 mm diameter spot (fluence of 2-6 J/cm2) on the lower half of
the neck. Patients were evaluated by two nontreating physicians as to overall
satisfaction and improvement in skin texture and color. RESULTS: Overall, 51% of
patients were satisfied with their results. Skin texture improved an average of
39%. Method 1 produced a 28% improvement, Method 2 a 48% improvement. Skin color
improved an average of 37%. Method 1 produced a 28% improvement, Method 2 a 45%
improvement. CONCLUSION: Photoaged skin of the neck can be effectively treated
with the Er:Yag laser with minimal adverse effects.
PMID- 10193961
TI - Long-term effects of one general pass laser resurfacing. A look at dermal
tightening and skin quality.
AB - BACKGROUND: Laser resurfacing with high-energy, short-pulsed lasers is generally
a safe and cosmetically rewarding procedure. Nevertheless, the aggressive use of
these instruments has the potential for unpredictable, undesirable complications.
It has long been held that multiple passes are needed to achieve dermal
tightening (collagen shrinkage), which will result in a cosmetically desirable
appearance. The observation of skin tightening after one general pass has not
been previously reported. OBJECTIVE: To look at the long-term results after only
one general pass and of focal multiple passes over lines, with particular
attention to the degree of tightening and quality of the skin. METHODS: Fifteen
patients with varying degrees of photodamage and resulting skin laxity, and with
at least eighteen months follow-up, were evaluated. High quality photographic
records were compared between pre- and postoperative pictures at three different
angles on each. RESULTS: Cosmetically significant dermal tightening was observed
in all of these patients. This was noted in some patients after six months and
continued for several months after. All patients were pleased with the cosmetic
improvement obtained. Of note were fast healing and the absence of significant
complications in these patients. CONCLUSIONS: The appearance of dermal tightening
as a late occurrence in the postoperative course after one single general pass
has not been previously reported. When numerous general passes are done, dermal
tightening is quite impressive and appears much sooner; however, much of this
result is due to edema and the resulting skin quality in these patients is
different. A more natural look is achieved if only one pass is done. The
procedure is safer and has a faster recovery period.
PMID- 10193962
TI - Long-term epilation with long-pulsed neodimium:YAG laser.
AB - BACKGROUND: Unwanted body hair can represent a severe cosmetic disturbance. The
traditional methods used to epilate often have limitations, side effects, and
unsatisfactory results. In recent years, various light sources (lasers and
others) have been developed for long-term epilation of unwanted hair. OBJECTIVE:
This study evaluates, on a large number of patients, the efficiency and safety of
a long-pulsed low-potency Nd-Yag laser invented specifically for long-term hair
removal. METHODS: Some 208 subjects needing epilation were divided into three
groups and treated during an 11-month period. Group A included 79 patients with a
normal distribution of unwanted hair; Group B 67 patients with constitutional
hypertrichosis; and Group C 62 patients with hirsutism. Treatment sessions were
performed with a fluence of 23-56 J/cm2 at 1-month intervals until obtaining
desirable results. Follow-ups ranged from 1 to 6 months. In 3 patients 4-mm
diameter punch biopsy specimens were obtained before the first session and again
after 6 hours. A third biopsy was performed after 3 months. RESULTS: Every
session resulted in a 20-40% hair loss, depending on the color of hair. Complete
epilation was obtained in 4 to 6 sessions. Only white hair was not receptive to
laser light, and its growth was not modified. No patients, including dark
complexioned patients, had blistering, hypo-or hyperpigmentation. No pain was
present during treatment except for the axillary area. In the specimen obtained
after 6 hours, very extensive necrosis of the hair follicular and sebaceous gland
epithelium was evident. Histologic findings of the biopsies taken after three
months showed complete disappearance of hair and moderate fibrosis. CONCLUSION:
This study proves that the long-pulsed Nd:Yag laser treatment produces an
excellent prolonged epilation with no relevant side effects. This laser light,
having a 1064 nm wavelength, is minimally absorbed in superficial skin layers,
and pronounced scattering up to 5 mm occurs targeting the deeper follicles.
PMID- 10193963
TI - The effect of glycolic acid on photoaged albino hairless mouse skin.
AB - BACKGROUND: Several clinical reports have suggested that alpha hydroxy acids
(AHAs), including glycolic acid, may improve photoaging. However, the mechanism
of action of glycolic acid is not well understood. OBJECTIVE: In order to
investigate the mechanism of action of glycolic acid in improving photoaged skin,
we observed the effect of glycolic acid on collagen metabolism and wrinkle
effacement in chronically ultraviolet B (UVB) irradiated mice. METHODS: Skh:HR-1
mice were exposed to UVB for 10 weeks and then treated topically with 15%
glycolic acid for 10 weeks. We assessed the improvement in wrinkling, the depth
of the dermal repair zone, and the extent of the increase in collagen synthesis.
RESULTS: At treatment week 10, the glycolic acid-treated mice showed a
significant decrease in wrinkle score, an increased thickness of the dermal
repair zone, and an increase in the amount of collagen synthesized compared to
vehicle (hydrophilic ointment base) treated mice. CONCLUSION: Topically applied
glycolic acid may improve photoaging through modulation of collagen production.
PMID- 10193964
TI - Does wound healing contribute to the eradication of basal cell carcinoma
following curettage and electrodessication?
AB - BACKGROUND: Histologic studies indicate that C&D fails to mechanically remove all
the tumor in a percentage of cases that far exceeds the 5-year recurrence rate.
This raises the question that if C&D does not mechanically remove the tumor in a
significant number of patients, why don't we observe tumor recurrence in most of
these patients? Our previous study indicates that inflammation occurring over 1
month following C&D does not clear residual tumor. It may be some other process,
requiring more time, that clears the residual tumor. Perhaps the proliferative or
maturation phase of wound healing or, alternatively, a slow-acting process such
as a low-grade immune response set in motion earlier, clears the residual tumor.
OBJECTIVE: To test the hypothesis that wound healing and maturation following C&D
clear residual tumor that has not mechanically removed by the procedure. METHODS:
The frequency of residual BCC detected histologically immediately following C&D
was compared with the frequency 3 months after the C&D, an amount of time in
which the maturation phase of wound healing is well under way. RESULTS: Twenty
two of 29 primary BCC less than 1 cm in size were tumor-free immediately
following the procedure (clearance rate 75.9%). Twelve primary BCC <1 cm were
treated by C&D, allowed to heal for 3 months, and then excised and checked
histologically. Ten of the twelve BCC were free of tumor, for a clearance rate of
83.3%, which is not a statistically significant difference (p = 0.7187).
CONCLUSION: By 3 months, the proliferative phase of wound healing is complete,
and our study indicates that this phase has no effect on clearing the tumor. The
maturation phase is well under way three months following C&D, and no
statistically significant effect was observed.
PMID- 10193965
TI - Suspension sutures aid facial reconstruction.
AB - BACKGROUND: Suspension, pexing or tacking sutures, which have a long history of
use in facial cosmetic surgery, have only recently begun use in reconstruction.
OBJECTIVE: In this study, the suspension suture was used to fix the closure line
at the junction of cosmetic units, to prevent distortion of free margins
secondary to wound contraction, eg, ectropion or eclabium, to prevent tenting
across concavities, and to prevent scar spreading of wounds closed under tension.
The acute complications and long-term effectiveness of this suturing technique in
achieving the 4 desired results were evaluated. METHODS: During a 10-year period,
136 cases of surgical defects of the face created by the removal of nonmelanoma
skin cancer by Mohs micrographic surgery were repaired using absorbable
suspension sutures. The wounds were evaluated initially for acute complications
of hemorrhage, infection, dehiscence, and necrosis; and later over 3 years for
chronic sequela of hypertrophic scar, spread scar, contraction deformities such
as distortion of free margins, and pigmentary changes. RESULTS: Suspension
sutures were used in 60 cases of primary layered closure and 76 flaps of the
face. Suspension sutures allowed primary closure of defects that would have
required flaps in 72% of the cases and prevented distortion of free margins.
There were more acute and long-term complications related to excess tension with
primary closure than with flaps. Suspension sutures fixed the closure line at the
junction of cosmetic units, prevented tenting across concavities, and both
features were maintained over the duration of the study. CONCLUSION: Suspension
sutures aided in obtaining linear closures, prevented distortion of free margins,
prevented tenting across concavities, and fixed the closure line at the junction
of cosmetic units; however, they did not prevent spread scars.
PMID- 10193966
TI - Acute excisional wounds treated with a tissue-engineered skin (Apligraf).
AB - BACKGROUND: Tissue-engineered products are usually composed of living cells and
their supporting matrices that have been grown in vitro, using a combination of
engineering and life sciences principles. Apligraf is a bilayered product
composed of neonatal-derived dermal fibroblasts and keratinocytes, and Type I
bovine collagen. OBJECTIVE: To evaluate in a prospective, multicentered open
study, the effects of tissue therapy with a tissue-engineered skin (Apligraf)
with partial or full-thickness excisional wounds. METHODS: One hundred and seven
patients participated in this study. The tissue-engineered skin was applied once,
immediately after excisional surgery, usually for skin cancer, and patients were
followed for up to one year. RESULTS: The safety results were impressive, with no
clinical or laboratory evidence of rejection. Clinically, graft persistence was
good to excellent in 77 of 105 (73.3%) of patients at one week, falling to 56.6%
and 53.6% at two weeks and one month respectively. CONCLUSION: To date, this is
the largest experience with a tissue-engineered skin product in acute wounds, and
this study suggests that tissue therapy may be safe and useful.
PMID- 10193967
TI - Comparison of the frequency-doubled Q-switched Nd:YAG laser and 35%
trichloroacetic acid for the treatment of face lentigines.
AB - BACKGROUND: Face lentigines are one of the manifestations of photodamaged skin
and often put people in socially embarrassing situations. Several lasers have
been used to remove lentigines at vast expense. However, trichloroacetic acid
(TCA) is an alternative for treating lentigines that costs much less. OBJECTIVE:
To compare the efficacy of the frequency-doubled Q-Switched Nd:YAG laser (532 nm)
and 35% TCA for the treatment of face lentigines. METHODS: Twenty patients
(Fitzpatrick skin Types III-IV) with a total of 37 lentigines on faces were
randomly collected; each lentigo was divided into medial and lateral halves.
Frequency-doubled Q-switched Nd:YAG laser (532 nm) and 35% TCA were applied to
the medial and lateral halves of each lentigo respectively. The efficacy after 1
treatment was compared after 6 months. RESULTS: The frequency-doubled Q-switched
Nd:YAG laser (532 nm) had a better result than that of 35% TCA for the treatment
of facial lentigines. CONCLUSION: In order to get a better result after one
treatment, the authors suggest the frequency-doubled Q-switched Nd:YAG laser (532
nm) rather than 35% TCA for treating lentigines even though the cost of frequency
doubled Q-switched Nd:YAG laser (532 nm) is greater than that of 35% TCA for both
physician and patient.
PMID- 10193968
TI - Adjuvant therapy with hyaluronidase prior to excision of dermatofibrosarcoma
protuberans.
AB - BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) are uncommon, low grade
cutaneous malignancies, which rarely metastasize. Although surgery is the main
therapy for these tumors, they commonly recur in spite of wide excisions.
Hyaluronidase (HD) has been used both intralesionally as well as intravenously as
an adjuvant in therapy of both epithelial and mesenchymal malignancies to
decrease local spread, to potentiate differentiation induced apoptosis, and to
potentiate the tissue penetration of chemotherapeutic agents. In addition, there
is a long history of intralesional HD use without significant complications. The
biologic characteristics of DFSP including the observation that hyaluronic acid
is commonly present and sometimes is increased in these tumors and the known
effects of HD therapy in other malignancies suggested to us that HD pretreatment
may be a helpful adjuvant in the surgical management of DFSPs. Following
diagnostic biopsy of a recurrent DFSP, the patient was treated for 4 weeks with
intralesional HD injections. RESULTS: Based on margins necessary for complete
excision from past studies, this patient had decreased margin width and thus had
a postoperative wound size less than was expected. The patient has had no
evidence of recurrence at 24 months follow-up.
PMID- 10193969
TI - Serial scalp reductions: a biomechanical approach.
AB - BACKGROUND: Several technical aspects of scalp-reduction procedures still need to
be clearly elucidated: in particular, (a) the quantitative effects provided by
different amounts of subgaleal undermining, (b) the immediate gains provided by
increasing amount of tension when advancing a scalp flap, and (c) the eventual
benefits provided by galeotomies. OBJECTIVE: The aim of the present paper is to
report on some biomechanical properties of scalp flaps as related to serial scalp
reduction procedures for correction of male pattern baldness. METHODS: Data were
collected by stepwise loading of 20 scalp flaps, obtained by a reversed-Y scalp
incision, after increasing amounts of undermining, as well as after performing
three galeotomies. RESULTS: Increasing amounts of tension (while advancing a
scalp flap) affect the compliance of a scalp flap in a non-linear fashion;
increasing amounts of undermining permit obtaining significant, but not
proportional, gains; performing galeotomies is a useful adjunct to decrease the
amount of closing tension when performing scalp-reduction procedures. CONCLUSION:
When performing serial scalp reductions, to take into account the biomechanics of
scalp flaps may be of some utility in obtaining an optimal result.
PMID- 10193970
TI - Modified purse-string closure for reconstruction of moderate/large surgical
defects of the face.
AB - BACKGROUND: Large surgical defects of the face can often be difficult to repair.
Extensive adjacent tissue transfer may be necessary and may result in significant
scars and possible flap compromise. Often there may be less donor tissue
available than is necessary to achieve closure. The alternative is a split
thickness skin graft, which often has a poor cosmetic outcome with poor color
match and contour irregularities. OBJECTIVE. A novel approach to closing large
surgical defects of the face is described. This relies on a combination of side
to-side bilateral advancement and circumferential tissue recruitment utilizing
the purse-string suture. METHODS: Report of illustrated cases. RESULTS: A 3.5 x
5.5 cm preauricular cheek defect, which could not be closed primarily side-to
side, was successfully completely closed in a curvilinear fashion by implementing
both side-to-side bilateral advancement and circumferential tissue recruitment. A
3.8 x 5.5 cm cheek defect and a 6.0 x 8.0 cm temple defect were significantly
decreased by using the modified purse-string closure. Healing by second intention
in these two cases provided an excellent cosmetic result. CONCLUSION: The use of
the purse-string closure utilizing circumferential tissue recruitment in
combination with side-to-side bilateral adjacent tissue transfer allows seemingly
large facial defects to be closed or significantly reduced in size. Such closure
is evident even in cases where poor skin laxity and size of the defect would not
appear to allow this. The modified purse string closure can result in an
excellent cosmetic outcome.
PMID- 10193971
TI - Tumescent liposuction in Germany: history and new trends and techniques.
AB - Due to the developments and changes of tumescent solution, infiltration
technique, and cannulas, we perform tumescent liposuction today using up to 6-8 l
tumescent solution. Total aspirate measures up to 9 l, pure fat aspired up to 5
l. Tumescent liposuction of extended areas can still be done as an outpatient
procedure. The condition of patients intra- and postoperatively as well as
results has improved and the predictability of outcome is more certain.
PMID- 10193972
TI - Treatment of inflamed hypertrophic scars using intralesional 5-FU.
AB - BACKGROUND: Hypertrophic scars and keloids may complicate wound healing secondary
to trauma or surgery. A variety of treatment regimens have been used with a range
of success. OBJECTIVE: The purpose of this paper is to report the use of 5
fluorouracil (5-FU) intralesionally in treatment of inflamed hypertrophic scars,
both as an individual agent as well as in conjunction with low-dose intralesional
corticosteroids plus pulsed dye laser therapy. METHODS: The author's 9-year
experience in the use of this agent in treating hypertrophic scars is summarized,
and case reports are used to demonstrate its efficacy at 50 mg/cc as well as
mixed with Kenalog (1 mg/cc) plus concomitant use of the pulsed dye laser.
RESULTS: Frequent initial injections (once to thrice weekly) were found to be
more efficacious with decreasing frequency (weekly to monthly) during a period of
stabilization and resolution of the scars. The combination of 5-FU and Kenalog
appeared to be more effective and less painful. The addition of the pulsed dye
laser treatments simultaneous with injection therapy was found to be most
effective. CONCLUSION: The use of 5-FU intralesionally for treatment of
hypertrophic scars appears to be both effective and safe. Further study is
warranted.
PMID- 10193973
TI - Management of multiple miliary osteoma cutis.
AB - BACKGROUND: Multiple miliary osteoma cutis of the face is a variant of osteoma
cutis that usually occurs in women with a previous history of acne vulgaris.
OBJECTIVE: To effectively treat cosmetically objectionable lesions of multiple
miliary facial osteomas. METHODS: We report a patient with multiple miliary
osteoma cutis, without a previous history of acne vulgaris, and the results of
treatment of these lesions with curettage and the carbon dioxide continuous-wave
laser. RESULTS: The patient had an excellent cosmetic outcome with minimal
scarring and faint hypopigmentation after 3 treatment sessions. CONCLUSION:
Surgical ablative therapy remains the treatment of choice for patients with this
condition, and the use of curettage and carbon dioxide laser ablation provided
excellent results for our patient. To our knowledge, this approach to treatment
has not been previously described.
PMID- 10193974
TI - Venous leg ulcers: modern evaluation and management.
AB - BACKGROUND: Venous leg ulcers are common in the adult population and cause a
significant social economic burden. Despite their prevalence, venous leg ulcers
are often managed inadequately. OBJECTIVE: To provide an overview of venous
ulceration, including a review of the current understanding of the
pathophysiology of venous ulceration and the implications for management of
venous ulceration. METHODS: A review of the literature. RESULTS: Modern methods
of investigation have led to an improvement in our understanding of the
pathophysiology of venous disease. In many patients, superficial and/or
perforator venous disease is the only underlying hemodynamic abnormality.
Although compression should serve as the cornerstone of treatment of venous
ulceration, surgery and/or sclerotherapy can treat incompetent superficial and
perforator veins. Important hemodynamic improvement is obtained, and the long
term prognosis of these patients is greatly improved. CONCLUSION: One must define
the basic underlying abnormality of the venous system to form a rational,
individualized management plan for the patient with venous ulceration.
PMID- 10193975
TI - Famciclovir prophylaxis of herpes simplex virus reactivation after laser skin
resurfacing.
AB - BACKGROUND: Cutaneous laser resurfacing with carbon dioxide and erbium:YAG lasers
has achieved remarkable clinical results with a relatively low risk of morbidity
and complications. The incidence of herpes simplex virus (HSV) reactivation after
resurfacing can be decreased by prophylaxis with antiviral agents. Famciclovir is
effective in the suppression and treatment of HSV infections; however, no studies
have examined the optimum dosing regimen for HSV prophylaxis in laser
resurfacing. OBJECTIVE: The objective of this study was to determine the efficacy
of 2 doses of famciclovir as prophylactic anti-HSV therapy during cutaneous laser
resurfacing. METHODS: Ninety-nine consecutive patients undergoing full-face laser
or perioral resurfacing received either 500-mg or 250-mg famciclovir twice daily,
beginning 24 hours prior to laser resurfacing and continuing for 10 days.
RESULTS: No HSV recurrences were seen in 90% of patients receiving famciclovir at
either dose. Approximately one-third of patients in each group with a positive
history of oral herpes labialis experienced HSV recurrence compared to 5% of
those without a known HSV history. CONCLUSIONS: Famciclovir 250-mg or 500-mg
twice daily is effective in the prevention of HSV recurrence in patients
undergoing cutaneous laser resurfacing. Based on our clinical experience, a 500
mg dose is suggested for patients with a strong history of HSV, while 250-mg
should be sufficient for those without prior HSV.
PMID- 10193976
TI - The treatment of bovine collagen allergy with cyclosporin.
AB - BACKGROUND: Bovine collagen is currently the most common substance used in soft
tissue augmentation. Although patients should undergo routine skin testing for
allergy to bovine collagen prior to treatment, hypersensitivity reactions may
rarely still occur. Previously, there have been no reliable methods of treatment
for these reactions, and physicians could only reassure patients that the
reaction would slowly disappear. OBJECTIVE. The use of oral cyclosporin in a
patient with hypersensitivity to bovine collagen was evaluated. METHODS: A
patient with an allergic reaction to implanted bovine collagen was started on
cyclosporin 175 mg p.o. bid (5 mg/kg/day) after no improvement was seen after
treatment with oral and topical steroids. The cyclosporin was started on Day 23
of the allergic reaction. RESULTS: Improvement in the itching and redness was
noted by Day 28 of the allergic reaction, and complete clinical resolution of the
allergic reaction was noted on Day 41. On Day 47, the cyclosporin was stopped
without recurrence of symptoms. The patient did not experience side effects from
cyclosporin, and her blood pressure and renal function remained normal.
CONCLUSION: This case report shows that oral cyclosporin A may be a safe and
effective treatment for bovine collagen hypersensitivity.
PMID- 10193977
TI - Possible hazards of cryogen use with pulsed dye laser. A case report and summary.
AB - BACKGROUND: Pulsed dye laser treatment of port-wine stains is safe and effective.
However, the pain associated with this treatment is often difficult to tolerate,
especially for children. A laser-coupled delivery system known as dynamic
epidermal cooling has recently been developed to improve local anesthesia.
OBJECTIVE: To report laser ignition of a commercially-available, hand-held
cryogen spray used for local anesthesia, and describe possible mechanisms of the
fire; to define the chemical characteristics of other skin coolants suitable and
unsuitable for skin cooling with laser treatment. METHODS: Case report and
literature review. CONCLUSIONS: Clinicians must be aware of the thermodynamic
properties, potential for skin damage, cost and environmental consequences of
commercially available cryogens before considering their use for topical
anesthesia with laser surgery.
PMID- 10193978
TI - Nevus spilus successfully treated with an intense pulsed light source.
AB - BACKGROUND: Nevus spilus is usually an acquired lesion that can present
therapeutic dilemmas for clinicians. OBJECTIVE: Using an intense pulsed light
source, a nevus spilus on the face of a 23-year-old woman was treated. METHODS:
The intense pulsed light source, utilizing a 590 nanometer filter, was used to
treat the nevus spilus. RESULTS: Four treatment sessions with the intense pulsed
light successfully treated the nevus spilus, and it has remained clear at the 6
month follow-up. CONCLUSIONS: Nevus spilus is a difficult condition to treat; the
intense pulsed light source should be considered in the armamentarium when
treating this condition.
PMID- 10193979
TI - Infections and occlusive dressings.
PMID- 10193980
TI - Additional graft donor sites for the nasal ala.
PMID- 10193981
TI - Varicose disease treatment.
PMID- 10193982
TI - Leg and foot sclerotherapy.
PMID- 10193983
TI - Resurfacing and punch excision for scarring.
PMID- 10193984
TI - Development of blood cardioplegia and retrograde techniques: the
experimenter/observer complex.
PMID- 10193985
TI - Invited commentary on the Ross procedure.
PMID- 10193986
TI - Aortic pulmonary autograft implant: medium-term follow-up with a note on a new
right ventricular pulmonary artery conduit.
AB - BACKGROUND: The Ross operation has been applied to various aortic valve
pathologies, particularly when somatic growth is an issue. However, associated
cardiac disease and technical problems may limit its use with regard to
associated procedures and issues of right ventricular outflow reconstruction.
MATERIALS AND METHODS: From December 1992 to March 1998, 24 patients underwent
aortic pulmonary autograft implantation. There were 14 males and 10 females, 15+/
10 years of age (mean +/- SD) (range 1 to 50 years), weighing 42.8+/-20 kg (mean
+/- SD) (range 8 to 78 kg). Aortic insufficiency was present in 15 (62.5%)
patients, stenosis in 8 (33.3%) patients, and valvar stenosis associated with
left ventricular outflow tract obstruction in 1 (4.1%) patient. Etiology was
rheumatic in 17 patients and congenital in 7. The Ross procedure was accompanied
by a partial-Konno left ventricular outflow enlargement in one patient, and
mitral valve annuloplasty, mitral commissurotomy, and tricuspid valve replacement
in three other patients, respectively. The right ventricular outflow was
reconstructed with a valved pulmonary homograft in 14 patients and with a
Shelhigh No-React porcine pulmonary conduit in 10 patients. Evaluation was done
by New York Heart Association (NYHA) Class and by echocardiography at a follow-up
of 22.8+/-24 months (mean +/- SD) (range 3 to 63 months). RESULTS: There were no
operative mortalities and no postoperative arrhythmias. One (4.1%) patient
required intra-aortic balloon pump (IABP) support for 3 days, one (4.1%) patient
died 2 years later of probable arrhythmia, and one (4.1%) patient required
mechanical aortic valve replacement 2 years later for severe autograft
insufficiency. Left ventricular ejection fraction was unchanged (preoperative
62.4%+/-30%, postoperative 64.2%+/-30% [mean +/- SD], [p = NS]) and no
significant gradient was documented by echocardiographic Doppler in the right and
left ventricular outflow tracts. The aortic insufficiency scale decreased from a
mean of 3.9+/-0.2 to a mean of 1+/-0 (p < 0.01). NYHA Class decreased to I in all
patients, from III (10) and II (14). CONCLUSIONS: The pulmonary autograft in the
aortic position is suitable for aortic valve replacement in pediatric and adult
patients with good medium-term results and in patients with rheumatic etiology,
and it provides a desirable solution in the presence of associated pathologies,
such as left ventricular tract obstruction or associated multivalvular disease.
The development of new means of right ventricular outflow reconstruction must
parallel the progress achieved for the left side.
PMID- 10193987
TI - Rest and exercise hemodynamics after the Ross procedure: an echocardiographic
study.
AB - BACKGROUND: Aortic prosthetic valves with superior hemodynamic performance are
associated with more complete regression of left ventricular hypertrophy and
better left ventricular function postoperatively. The near normal function of the
pulmonary autografts at rest is well documented, however, exercise data has been
seldom reported. The purpose of this study is to evaluate the hemodynamic
performance of pulmonary autografts in the aortic position and the homografts
used to reconstruct the right ventricular outflow tract during conditions of high
cardiac output by means of dobutamine stress echocardiography. METHODS: Between
May 1995 and February 1998, 67 patients were submitted to a Ross operation at our
institution. Twenty of these patients had a mean age of 28.6+/-8.3 years and a
mean follow-up time of 15.7+/-5.9 months. They were studied by dobutamine stress
echocardiography to evaluate rest and exercise hemodynamics of the pulmonary
autografts as well as of the aortic and pulmonary homografts used to reconstruct
the right ventricular outflow tract. Dobutamine infusion was started at 5
microg/kg with incremental doses up to 40 microg/kg in every case. RESULTS: With
dobutamine infusion, heart rate increased from 71+/-10 to 142+/-11 beats/min,
left ventricular systolic volume from 86.8+/-33.9 mL to 115.9+/-52.6 mL, and
cardiac output from 6.3+/-2.9 L/min to 16.8+/-7.4 L/min. Left ventricular
function was considered satisfactory at rest and during exercise in all patients.
The mean gradient across the autograft increased from 1.03+/-0.95 mmHg to 4.03+/
2.05 mmHg and maximal instantaneous gradient from 2.45+/-2.21 mmHg to 9.54+/-4.85
mmHg. The mean effective orifice area for the autografts were 3.5+/-1.3 cm2 at
rest and 3.3+/-1.4 cm2 during exercise. The patients with mild aortic
insufficiency at rest had no increase in the degree of regurgitation with
exercise. In the right ventricular outflow tract, the mean gradient across the
homograft increased from 9.06+/-5.29 mmHg to 17.55+/-9.76 mmHg and maximal
instantaneous gradient from 21.4+/-12.5 mmHg to 41.5+/-23.1 mmHg. CONCLUSIONS:
Pulmonary autografts exhibit normal hemodynamic performance at rest and during
exercise after the Ross operation. However, mild-to-moderate gradients are common
at the right ventricular outflow tract and should be carefully monitored.
PMID- 10193988
TI - Options for right ventricular outflow tract reconstruction.
AB - The popularity of the Ross operation has drawn attention to the need for a
satisfactory replacement of the excised pulmonary valve and artery. Although
living autogenous tissue is desirable, it has not been possible to manufacture a
satisfactory living conduit, and pulmonary homografts have provided a
satisfactory long-term solution. Now, with the increasing shortage of homografts,
a number of alternative options have to be considered. The most useful and
readily acceptable replacement is a porcine pulmonary xenograft, which is now
commercially available. Other prospects for future consideration relate to the
use of transgenic pig tissue and developing techniques of tissue engineering. In
emergency conditions where a valve conduit is unavailable, a temporary solution
is to use a simple tube of autogenous pericardium.
PMID- 10193989
TI - Early results using an ePTFE membrane for pericardial closure following coronary
bypass grafting.
AB - A prospective randomized trial was conducted to evaluate the early efficacy and
safety of the Gortex surgical membrane. Three hundred two patients (265 males, 37
females) undergoing isolated coronary bypass surgery were randomized to receive a
Gortex membrane (GM = 138) or have the pericardium left open (complication [C] =
164). The groups did not differ in age, gender, urgency of procedure, length of
procedure, or use of arterial grafts. Two deaths occurred in each group giving an
overall mortality of 1.3%. Fifty-three (17%) patients experienced some
complication (C = 34, 21%), GM = 19 (14%). Although the combined complication
rate was higher in the control group, this was not statistically significant
(chi2 = 2.51, p = 0.11). Postoperative ischemic events (C = 8, GM = 4) observed
between the groups were not significant (chi2 = 0.05, p = 0.8), and no
statistically significant difference was observed between the incidences of
infections (C = 7, GM = 5) or mediastinal complications (C = 3, GM = 3). The
Gortex surgical membrane can be used safely without increasing the risk of
infection or mediastinal complications. The incidence of recurrent myocardial
ischemia, a possible indicator of graft compression, was not higher following
membrane implantation. Efficacy at injury prevention will need to be determined
by a longitudinal follow-up study presently underway.
PMID- 10193990
TI - Prevalence of aortocoronary graft marker use and the factors affecting this
decision.
AB - BACKGROUND: Despite quantifiable evidence that aortocoronary graft marker (ACGM)
insertion is associated with a beneficial impact at postoperative angiography,
the choice whether or not to insert them at the time of bypass surgery remains
optional. METHODS: A one-time anonymous membership survey of the Society of
Thoracic Surgeons was used to determine the prevalence of ACGM use and obtain
demographic data regarding (1) the type of ACGM inserted, (2) reasons influencing
the decision as to whether or not to use ACGMs, and (3) the occurrence of
possible related complications. RESULTS: Thirty-nine percent (1,405 of 3,558) and
37% (198 of 531) were returned from within and outside the Unites States,
respectively. Sixty percent of US respondents routinely insert ACGMs in the
majority of their individual cases. The most frequent reason to not insert ACGMs
was a "lack of perceived benefit." CONCLUSIONS: The majority of respondents
practicing within the United States routinely insert ACGMs at the time of
surgery. As no complication directly attributable to the use of graft markers has
been reported, further study is warranted to determine the actual complication
rate, although it is expected to be low.
PMID- 10193991
TI - Surgical treatment for aortic regurgitation caused by Takayasu's arteritis.
AB - Aortic regurgitation (AR) caused by Takayasu's arteritis is relatively rare. We
investigated the surgical results in patients with AR caused by Takayasu's
arteritis. Between 1978 and December 1997, 65 patients (5 males, 60 females) with
AR secondary to Takayasu's arteritis underwent surgery. The patients' ages ranged
from 19 to 70 years (mean, 48 years). Takayasu's arteritis was diagnosed by
clinical examination confirmed by intraoperative pathological examination of the
aortic wall. The surgical procedures for AR were aortic valve replacement in 45
patients, Bentall-type operation in 19, and remodeling in 1. Four (6.2%) patients
died during the hospital stay. The follow-up period ranged from 3 to 227 months
(mean, 111 months). Eleven patients died during the follow-up period, and the
actuarial survival rate was 87% at 5 years and 75% at 10 years. The incidence of
prosthetic valve detachment was 4.6% (3/65). Three patients required a composite
graft replacement. No prosthetic valve detachment was noted in 96% of the
patients at 5 years and in 94% at 10 years. Preoperative steroid administration
to treat inflammation and its postoperative use to control inflammation may be
important in the treatment of these patients.
PMID- 10193992
TI - Aortic valve replacement with medtronic freestyle bioprosthesis: operative
technique and results.
AB - OBJECTIVE: This study evaluates the initial results for safety and efficacy of
aortic valve replacement (AVR) using the Medtronic Freestyle Bioprosthesis.
METHODS: One hundred three patients underwent AVR with the Medtronic Freestyle
Bioprosthesis over a 40-month period. There were 59 male and 44 female patients
with a mean age of 74 years (range 36 to 88 years). Valve size ranged from 19 to
27 mm, and all valves were implanted using a freehand subcoronary technique.
Anticoagulation with coumadin was only used for atrial fibrillation. Aspirin was
given to patients with associated coronary artery disease. Echocardiography to
assess transvalvular pressure gradient and effective valve orifice area was
performed at discharge, 3 to 6 months, 1 year, and then annually. RESULTS: There
were 4 (3.9%) deaths within 30 days of operation and 5 (4.9%) late deaths. Two
(1.9%) deaths were valve-related, one from commissural dehiscence and one from
bacterial endocarditis. Three (2.9%) deaths, two early and one late, were from
other cardiac causes. The remaining deaths were from noncardiac causes. Five
(4.9%) patients suffered a thromboembolic event, two had permanent neurological
deficits, two had transient neurological events, and one had coronary artery
occlusion. Mean transvalvular gradient assessed by echocardiography was low at
all time intervals: discharge (12.8 mmHg), 3 to 6 months (11.3 mmHg), 1 year
(12.0 mmHg), and 2 years (11.6 mmHg). Mean effective valve orifice area was good
at all time intervals: discharge (1.4 cm2), 3 to 6 months (1.5 cm2), 1 year (1.6
cm2), and 2 years (1.6 cm2). Of the 38 patients assessed by echocardiography at 1
year, 33 (87%) had no or trivial valve incompetence and the remainder had mild
valve incompetence. CONCLUSIONS: Aortic valve replacement with the Medtronic
Freestyle Bioprosthesis has a low incidence of early valve-related mortality and
thromboembolism. The bioprosthesis demonstrates good hemodynamic performance even
in small diameters and is particularly well suited for older patients and the
small aortic root.
PMID- 10193993
TI - Phrenic nerve injury following cardiac surgery: a review.
AB - Phrenic nerve injury following cardiac surgery is variable in its incidence
depending on the diligence with which it is sought. Definitive studies have shown
this complication to be related to cold-induced injury during myocardial
protection strategies and possibly to mechanical injury during internal mammary
artery harvesting. The consequences are also variable and depend to a large
extent on the underlying condition of the patient, particularly with regard to
pulmonary function. The response of the patient may range from an asymptomatic
radiographic abnormality to severe pulmonary dysfunction requiring prolonged
mechanical ventilation and other associated morbidities and even mortality. Two
cases are presented to demonstrate the variability in clinical responses to
diaphragmatic dysfunction secondary to phrenic nerve injury from cardiac surgery.
In addition, treatment strategies are reviewed including early tracheostomy and
diaphragmatic plication, which appear to be the most effective options for
patients who are compromised by phrenic injuries.
PMID- 10193995
TI - Management of temporary epicardial ventricular pacing wires.
PMID- 10193994
TI - Prevention of ischemic damage using controlled limb reperfusion.
AB - Following prolonged limb ischemia, a reperfusion injury may occur with the
reintroduction of unmodified blood, resulting in tissue loss and, in severe
cases, limb loss. We have shown that the reperfusion injury in the heart can be
minimized by using controlled reperfusion with a substrate-enriched cardioplegia
solution prior to restoring normal blood flow. This article describes two
clinical cases in which we used controlled reperfusion in an ischemic limb to
prevent limb loss. It demonstrates that a controlled, substrate-enhanced,
hypocalcemic, leukodepleted, modified blood reperfusate solution can minimize
limb reperfusion damage and improve functional recovery. This preliminary
experience is presented to familiarize surgeons with this form of treatment and
to describe the solutions and method of administration that can be used to avoid
the devastating complications of severe limb ischemia.
PMID- 10193996
TI - The unmet anti-inflammatory needs in orthopedics.
AB - Approximately half of Americans 70 years of age or older suffer from arthritis.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most effective
nonsurgical therapies for arthritis, but usage often causes harmful side effects,
especially in the gastrointestinal tract. Such effects require supplemental
therapy that adds an economic burden and may even cause death. The benefits
derived from NSAIDs are believed to be due to suppression of cyclooxygenase-2
(COX-2), while the harmful side effects are believed to be due to suppression of
cyclooxygenase-1 (COX-1). COX-2-specific inhibitors that do not inhibit COX-1 may
meet arthritis sufferers' needs for therapies that are safe, convenient, and as
effective as conventional NSAIDs.
PMID- 10193997
TI - Role of cyclooxygenase-1 and -2 in health and disease.
AB - Animal and human data demonstrate that cyclooxygenase (COX)-2 upregulation in
osteoarthritis and rheumatoid arthritis is associated with the pain and
inflammation of the disease state. The COX-1 isoform, however, is a constitutive
enzyme with homeostatic functions. Unlike conventional nonsteroidal anti
inflammatory drugs, which inhibit both forms of the COX enzyme, celecoxib
inhibits COX-2 preferentially to COX-1 in vitro. Celecoxib reversed signs of
arthritis and pain in an animal model as effectively as indomethacin. Data from
murine studies as well as in vitro and epidemiologic data indicate that COX-2
plays a role in the development of colon cancer, and epidemiologic studies also
suggest that COX inhibition can slow the progression of Alzheimer's disease.
PMID- 10193998
TI - Celecoxib, a COX-2--specific inhibitor: the clinical data.
AB - Celecoxib offers the unique therapeutic prospect of alleviating pain and
inflammation without the untoward gastrointestinal, renal, and platelet effects
associated with conventional nonsteroidal anti-inflammatory drugs. This is
possible because celecoxib is a cyclooxygenase-2 (COX-2)-specific inhibiting
agent that inhibits the conversion of arachidonic acid to the prostaglandins that
mediate pain and inflammation while having no effect on the formation of the
prostaglandins that mediate normal homeostasis in the gastrointestinal tract,
kidneys, and platelets and that are formed under the control of cyclooxygenase-1
(COX-1). Double-blind clinical trials have demonstrated that celecoxib is as
effective in ameliorating the signs and symptoms of osteoarthritis and rheumatoid
arthritis as naproxen and as effective as aspirin in reducing pain following
dental extraction. Controlled trials have also shown that the incidence of
gastroduodenal ulcers and the combined incidence of gastroduodenal ulcers and
erosions are significantly lower with celecoxib therapy than with naproxen
therapy and are similar to those associated with placebo administration. In a
study of platelet function, it was found that a single 650-mg dose of aspirin
profoundly diminished platelet function, while therapeutic doses of celecoxib
exhibited no such effect. Celecoxib has been shown to be well tolerated, with
incidences of adverse events similar to placebo in most instances. In summary,
evidence to date indicates that celecoxib is a safe and effective therapeutic
modality for the management of arthritis and pain.
PMID- 10193999
TI - Practical implications of cyclooxygenase-2--specific inhibitors in orthopedics.
AB - Nonsteroidal anti-inflammatory drugs (NSAIDs) lead to severe and unpredictable
side effects that are costly for individuals and the economy overall. As baby
boomers enter their osteoarthritis years, there will be an increasing demand for
safe and effective arthritis therapies. Animal and human data suggest that
celecoxib, a cyclooxygenase-2-specific inhibitor, will provide an efficacious
treatment without the side effects of conventional NSAIDs. Clinicians will need
to determine individually and collegially how best to incorporate this new class
of drugs into comprehensive treatment algorithms.
PMID- 10194000
TI - The management of pain and inflammation in orthopedic medicine: question-and
answer period.
PMID- 10194001
TI - The world according to the hand: observation, art, and learning through the sense
of touch.
PMID- 10194002
TI - Hearing as substitution for sensation: a new principle for artificial
sensibility.
AB - We describe a new principle for artificial sensibility of the hand based on sense
substitution, using hearing as substitution for loss of sensation. The
experiments were performed on 3 patients who had recently undergone isolated
median nerve repair, 1 patient with replantation of an amputated forearm, 1
patient using a myoelectric prosthesis, and 4 patients using cosmetic prostheses.
Small condenser microphones were mounted dorsally on the distal phalanges of
multiple fingers of the nonsensate hands or prostheses. The friction sound,
reflecting the vibrotactile stimuli generated by the moving touch of the objects,
was picked up by the microphones and processed in a stereo amplifier that
separated signals from individual fingers into different channels. The signals
were transmitted to earphones, making possible a spatial resolution that enabled
identification of each finger by the generated acoustic stimuli. Since the
friction sound is characteristic of specific surfaces and textures, the
corresponding acoustic stimuli made possible identification of different
textures, such as glass, metal, wood, and paper, without using vision. We
conclude that sense substitution using specifically processed acoustic stimuli as
a substitute for sensation may represent a useful principle for generation of
artificial sensibility in prostheses or hands lacking sensibility due to lesions
in the peripheral or central nervous system or because of neurologic disease.
PMID- 10194003
TI - Occult scapholunate ganglion: a cause of dorsal radial wrist pain.
AB - There are multiple causes for chronic dorsal wrist pain over the scapholunate
ligament, including occult dorsal carpal ganglion cyst, scaphoid impaction
syndrome, dorsal carpal capsulitis, distal posterior interosseous nerve syndrome,
and dynamic scapholunate ligament instability. Patients with such pain often have
normal x-rays. A retrospective study of 21 patients undergoing surgical
exploration for chronic dorsal radial wrist pain who had no palpable cyst and
normal x-rays revealed that 18 of the patients had occult scapholunate ganglion
cysts or myxomatous degeneration within the scapholunate ligament. All had failed
long-term conservative management. Surgery involved an approach through Langer's
lines, resection of a large triangular portion of the capsule between the dorsal
intercarpal and radiotriquetral ligaments, and tangential debridement of the area
of myxoid degeneration proximal to the distal 2 to 3 mm of dorsal scapholunate
interosseous ligament. None of the patients had scapholunate instability or
scaphoid impacting syndrome. Of the 18 patients with histologically confirmed
myxomatous changes in the scapholunate ligament, 16 had an excellent outcome as
defined by rigorous criteria; 1 had a good outcome. There was 1 patient with a
poor result. A compelling argument is made for surgical exploration of the
scapholunate joint in patients with persistent dorsal radial wrist pain and
scapholunate point tenderness.
PMID- 10194004
TI - Dorsal intercarpal ligament capsulodesis for scapholunate dissociation:
biomechanical analysis in a cadaver model.
AB - The purpose of this study was to evaluate in cadavers a new method for treating
scapholunate dissociations, dorsal intercarpal ligament capsulodesis (DILC), and
to compare its performance with that of a previously described soft tissue
reconstruction, Blatt capsulodesis (BC). A cadaver model was used to simulate
normal and abnormal wrist motions. The positions of the scaphoid and lunate and
their changes with wrist motion and ligament condition were recorded using
biplanar radiographs taken posteroanteriorly and laterally. The scapholunate gap
was measured on the posteroanterior radiographs and the scapholunate angle was
measured on the lateral view radiographs. Following scapholunate interosseous
ligament sectioning, a diastasis developed between the scaphoid and lunate that
was maximum in the clenched fist position 2.1 +/- 0.33 mm (mean +/- SEM) with the
ligament intact versus 8.0 +/- 1.74 mm after the ligament was sectioned. Dorsal
intercarpal ligament capsulodesis reduced gap formation more than BC, including
when the specimens were in the clenched fist position: increased gap versus
intact specimens equals 1.0 mm for DILC versus 3.7 mm for BC. The differences in
diastasis were statistically significant between BC and DILC when the wrist was
in extension, radial deviation, and clenched fist positions. After the
scapholunate interosseous ligament was divided, the scaphoid flexed relative to
the lunate. Both capsulodeses improved scapholunate alignment and there was a
trend for DILC to correct the scapholunate angle more than BC. The results
demonstrate that DILC is an attractive alternative to BC ex vivo. Because DILC
does not tether the scaphoid to the distal radius, as BC does, improved wrist
motion, especially flexion, might be possible in vivo. The use of DILC in the
treatment of scapholunate dissociation warrants further investigation and
clinical trials.
PMID- 10194005
TI - Complete avulsion of the distal posterior interosseous nerve during wrist
arthroscopy: a possible cause of persistent pain after arthroscopy.
AB - A case of avulsion of the distal posterior interosseous nerve during wrist
arthroscopy is presented. Surgeons unaware of this entity may attribute
persistent middorsal wrist pain to the underlying disease rather than to
iatrogenic damage to the distal posterior interosseous nerve.
PMID- 10194006
TI - Septic arthritis and osteomyelitis of the wrist: reconstruction with a
vascularized fibular graft.
AB - A case of spontaneous staphylococcus arthritis of the wrist with associated
carpal and distal radius osteomyelitis is reported. Following sequential
debridements and a 6-week course of parenteral antibiotics, an extensive defect
was bridged with a vascularized fibular autograft to achieve a successful fusion.
There was no donor site morbidity or recurrent infection. Follow-up radiographs
41 months later demonstrated complete incorporation and hypertrophy of the graft.
PMID- 10194007
TI - Tilted lateral radiographs in the evaluation of intra-articular distal radius
fractures.
AB - The anatomy of the distal radius confounds the assessment of fracture
displacement of the lunate facet. Since reduction of the articular surface is
paramount to obtaining good clinical results, this study was designed to evaluate
whether a radiograph taken 22 degrees from true lateral (forearm held at a 22
degrees angle from the horizontal film cassette) would enhance the accuracy of
measuring displacement. Fifteen lunate facet fractures of varying depression were
produced in 7 fresh cadaveric wrists. Posteroanterior (PA), standard lateral, and
22 degrees tilted lateral radiographs were obtained of each fracture pattern.
Four observers reviewed the films and measured the depression of the fragments
from their anatomic position. Measurement error from actual depression averaged
1.1 mm when the evaluators evaluated the 22 degrees lateral and PA films, 1.5 mm
for the standard lateral and PA views, and 0.8 mm for the standard lateral, 22
degrees lateral, and PA radiographs (combined group). The decrease in measurement
error obtained from all 3 groups was statistically significant. The results of
this study suggest that the 22 degrees tilted lateral, either in combination with
the standard lateral radiograph or just with the PA view, may help the hand
surgeon better understand the intra-articular depression of lunate facet
fractures of the distal radius.
PMID- 10194008
TI - Ultrasound diagnosis and surgical pathology of the torn interosseous membrane in
forearm fractures/dislocations.
AB - Ultrasound was used to effectively diagnose and precisely locate a torn
interosseous membrane in 2 forearm fracture/dislocations. The ultrasound
appearance of the torn interosseous membrane in cadavers and in the
fractures/dislocations shows disruption of the anterior and posterior layers in
midsubstance or adjacent to the radius or ulna. The surgical pathology in 3
forearm fractures/dislocations (2 Galeazzi injuries and 1 Essex-Lopresti injury)
shows a longitudinal oblique tear of the interosseous membrane, parallel to its
major palmar fibers, oriented from proximal radial to the distal ulnar. After
ultrasound diagnosis, we demonstrated the feasibility of direct primary repair of
the torn interosseous membrane associated with the Essex-Lopresti injury in a
clinical case.
PMID- 10194009
TI - Early results with osseointegrated proximal interphalangeal joint prostheses.
AB - Osseointegrated endoprostheses were used in 22 proximal interphalangeal joint
replacements in 12 patients between 1993 and 1995. Indications for surgery were
joint destruction due to rheumatoid arthritis (13 joints), primary osteoarthrosis
(7 joints), posttraumatic arthrosis (1 joint), and psoriatic arthritis (1 joint).
The prostheses consisted of 2 screw-shaped titanium fixtures with a flexible
silicone spacer. The 1-stage surgical procedure included joint resection and
cancellous bone grafting from the iliac crest before insertion of the titanium
fixtures. At a follow-up examination 27 months (range, 12-37 months) after
surgery, the average active range of motion was 56 degrees (20 degrees to 80
degrees) with an extension lag of 11 degrees (-5 degrees to 45 degrees),
corresponding to an average arc of motion of from 11 degrees to 67 degrees
flexion. Radiographs indicated that 41 of 44 fixtures were osseointegrated. Four
of the 22 joint mechanisms showed fracture of the silicone spacer; deformation of
the silicone was noted in an additional 27%. Patient satisfaction was high (20 of
22 joints), with significantly improved range of motion and hand function,
increased grip strength, good pain relief, and satisfactory appearance. The
results of this study indicate good early clinical findings using osseointegrated
implants for proximal interphalangeal joint replacement but also show the need
for further development regarding the durability of the flexible silicone joint
spacer.
PMID- 10194010
TI - Outcome of avulsion fractures of the ulnar base of the proximal phalanx of the
thumb treated nonsurgically.
AB - We report a retrospective study of avulsion fractures of the ulnar collateral
ligament of the thumb metacarpophalangeal joint that were treated nonsurgically.
The study included 30 patients who answered a questionnaire. None of the patients
underwent surgery after treatment. The average follow-up interval was 3.1 years
(range, 1-5.2 years). All 30 patients were satisfied with the treatment and
outcome. No patient had a permanent job change or inability to participate in
recreational activities. Nineteen patients had no pain on motion of the thumb. Of
the 20 patients (67%) who agreed to a follow-up examination, key pinch and grip
strength were not statistically different between the injured and noninjured
sides. Three patients had instability on stress testing. There was a 25% nonunion
rate. While not statistically significant, symptomatic patients tended to have
slightly larger fragments (5.4 mm x 1.7 mm vs 3.2 mm x 1.4 mm on anterioposterior
x-rays) and greater initial rotation (26 degrees vs 24 degrees) of the fracture
than asymptomatic patients. Despite the nonunion rate and the patients with
clinical instability, all 30 patients were satisfied with their treatment.
PMID- 10194011
TI - The effect of thumb metacarpophalangeal ulnar collateral ligament attachment site
on joint range of motion: an in vitro study.
AB - Although reconstruction of the torn thumb metacarpophalangeal (MCP) joint ulnar
collateral ligament (UCL) has been shown to reduce symptoms, final joint motion
may be different from that of the uninjured state. It was hypothesized that
nonanatomic repositioning of the UCL might affect joint motion; therefore, the
effect of UCL attachment site on MCP range of motion was investigated. The UCL
and MCP joint capsule were visualized in each of 8 fresh cadaveric hands without
otherwise disrupting the joint. The centers of the ligament attachments were
marked with pins and each specimen was mounted on a testing frame capable of
applying loads through the flexor and extensor tendons. After measuring the
flexion, extension, and radial and ulnar deviation ranges of motion of the intact
specimen, the origin of the ligament (on the metacarpal) and an attached bone
block were elevated and repositioned 2 mm proximal and 2 mm palmar and range of
motion was tested. The origin was reattached in its anatomic location and the
insertion of the ligament was similarly elevated and displaced 2 mm in distal,
dorsal, and palmar directions. Compared with the intact joint, palmar placement
of the UCL origin on the metacarpal increased radial deviation (from a mean of 18
degrees to a mean of 27 degrees); proximal placement of the origin decreased it
(from 18 degrees to 10 degrees). Similarly, dorsal placement of the UCL insertion
on the phalanx increased radial deviation (from 18 degrees to 25 degrees) and
distal positioning of the insertion decreased it (from 18 degrees to 11 degrees).
Relative to intact joint flexion range of motion (mean, 57 degrees), distal
placement of the UCL phalangeal insertion restricted motion (mean, 47 degrees),
as did palmar placement (mean, 48 degrees). Extension and ulnar deviation motions
were unaffected by ligament attachment position. This study demonstrates that
nonanatomic reconstruction of the UCL alters normal MCP joint range of motion.
PMID- 10194012
TI - Results of proximal interphalangeal joint release for flexion contractures:
midlateral versus palmar incision.
AB - Forty-two patients (45 fingers) were retrospectively reviewed after operative
release of flexion contractures of the proximal interphalangeal (PIP) joint. The
release was accomplished through a palmar incision in 19 fingers, usually
followed by skin coverage using a lateral transposition flap. A midlateral
incision was used in 26 fingers. The 2 groups were comparably matched with
respect to degree of contracture and demographic characteristics. Active range of
motion (ROM) was measured before and after surgery. In the palmar incision group,
preoperative median PIP joint ROM was 60 degrees to 90 degrees
(extension/flexion) and 30 degrees to 90 degrees at the 3-year follow-up
examination. In the midlateral incision group, preoperative median PIP joint ROM
was 50 degrees to 90 degrees (extension/flexion) and 0 degrees to 90 degrees at
the 1.5-year follow-up examination. The improvement in ROM was significantly
better in the midlateral incision group than in the palmar incision group.
PMID- 10194013
TI - Biomechanical analysis of the cruciate four-strand flexor tendon repair.
AB - The purpose of this study was to develop and test in vitro a new flexor tendon
suture technique that was simple and easy to perform, yet strong enough to
withstand the projected forces of an in vivo active motion rehabilitation
protocol. Forty human cadaveric flexor digitorum profundus tendons were divided
and repaired using 1 of 4 suture techniques (the modified Kessler, the
Strickland, the modified 4-strand Savage, and the Cruciate 4-strand repairs).
Each repair was tested using a slow-test machine and displacement control at 2
mm/s. Force applied, the resultant gap, and ultimate tensile strength were
recorded and statistical comparisons were performed using a two-tailed Student's
t-test with level of significance set at p = .05. The Cruciate suture technique
was demonstrated to be nearly twice as strong to 2-mm gap formation (44 N)
compared with the Kessler, Strickland, and Savage repairs. Ultimate tensile
strength was also significantly stronger for the Cruciate technique (56 N) than
the Kessler, Strickland, or Savage repairs. The technique was significantly
faster to perform than the Savage or Strickland repairs and was comparable in
repair time to the 2-stranded Kessler repair. The design of the new suture
technique allowed the tendon repair to be completed with the ease and speed of a
2-strand technique, but bestowed on the repair strength that exceeded current 4
strand techniques.
PMID- 10194014
TI - Effects of tenorraphy on the gliding function and tensile properties of partially
lacerated canine digital flexor tendons.
AB - Management of a partially lacerated digital flexor tendon within zone II remains
controversial. To address this issue, we undertook an evaluation of the impact of
tenorrhaphy on the gliding function and tensile properties of canine flexor
tendons with lacerations involving either 30% or 70% of their cross-sectional
area. Assessment of tendon excursion and joint rotation after 6 weeks of
postoperative controlled passive mobilization failed to reveal any statistically
significant benefit from tenorrhaphy on the gliding function. In fact, we
demonstrated a significant negative effect of repair on tendons with 30%
lacerations. Moreover, no significant differences between the structural
properties or integrity of the repaired and nonrepaired tendons could be
demonstrated. Thus, in light of the inherent tensile properties in these
partially lacerated tendons, our data suggest that digital function of partially
lacerated tendons of up to 70% of the cross-sectional area may be preserved
without primary repair. However, additional work is needed to more definitively
address this issue in a clinical context.
PMID- 10194015
TI - Feasibility of partial A2 and A4 pulley excision: effect on finger flexor tendon
biomechanics.
AB - We investigated the effect of partial excision of the A2 and A4 digital pulleys,
separately and in combination, on finger angular rotation and the energy for
finger flexion. Statistically significant decreases in angular rotation resulted
only after 50% and 75% excision of A2, A4, or A2 and A4 in combination. Work of
flexion trends were weak and none of the changes were statistically significant.
Although optimal finger function relies on the integrity of the A2 and A4 pulleys
to maintain the efficiency of the digital flexor system, these data suggest that
the A2 and A4 pulleys can be excised up to 25%, either separately or in
combination, without significant effects on angular rotation. Decreases in total
angular range of motion after 50% and 75% pulley excision were small, even for
combined pulley excision (9 degrees +/- 3 degrees and 15 degrees +/- 5 degrees
[mean +/- SD], respectively), and may be clinically acceptable.
PMID- 10194016
TI - Abducted, hyperextended small finger deformity of nonneurologic etiology.
AB - The abduction and hyperextension deformity of the small finger is usually
associated with ulnar nerve palsy. Six patients who sustained an abduction force
to their small finger presented with the finger in an abducted and hyperextended
position. All patients were neurologically intact and were unable to adduct or
flex the finger at the metacarpophalangeal joint. Surgical findings in these
patients included rupture of the radial sagittal band, collateral ligament, and
junctura tendinum. Sequential division of these structures in cadaveric hands
confirmed that all these tissues had to be deficient for this deformity to occur.
The traumatic abducted, hyperextended small finger deformity may respond to
conservative treatment, but surgery is sometimes necessary.
PMID- 10194017
TI - A method of restoration of the abduction of the thumb in traumatic tetraplegic
patients.
AB - A method of restoring extension and abduction of the thumb in traumatic
tetraplegia is described. This method includes tenodesis of the abductor pollicis
longus, transfer of the distal stump of the extensor pollicis brevis tendon to
the flexor carpi radialis tendon, and transfer of the distal stump of the
extensor pollicis longus tendon to the brachioradialis tendon. I performed this
procedure on 6 hands in 5 patients and monitored each patient for 6 to 12 months.
A significant increase in radial abduction of the thumb (0.5 +/- 0.2 cm to 2.8 +/
0.2 cm) occurred in all hands.
PMID- 10194018
TI - Upper extremity surgical treatment of cerebral palsy.
AB - The purpose of this report is to review the surgical treatment of the upper
extremity involved with cerebral palsy over a 25-year period and present our
results with regard to changes in upper limb function. Surgical results were
assessed by comparison of preoperative and postoperative levels of upper
extremity functional use using a previously described 9-level scale. The effect
of the following cofactors on surgical outcome were examined: type of cerebral
palsy, age, voluntary control, mental impairment, sensibility, and type of
surgical treatment. One hundred eighty operations representing 718 procedures in
134 patients were reviewed. Surgical treatment was based on the following
principles: soft tissue releases of deforming spastic muscles, tendon transfers
to augment antagonistic activity, and joint stabilization. Surgical planning was
tailored to each child's particular needs. Comparison of the preoperative and
postoperative 9-level functional use scores showed an average improvement of 2.6
functional levels for all patients. Patients with fair and good voluntary control
had significantly greater improvement in functional use scores than those with
poor voluntary control. No other statistically significant predictive cofactor
was found. In selected patients with upper extremity dysfunction secondary to
spastic cerebral palsy, surgical intervention improves function, as measured by
the upper extremity functional use scale.
PMID- 10194019
TI - Lengthening of pediatric forearm deformities using the Ilizarov technique:
functional and cosmetic results.
AB - Eight patients (average age, 10 years) had a unilateral forearm lengthening
procedure using the technique developed by Ilizarov. The procedure was performed
in 4 patients with radial agenesis, in 2 with multiple hereditary exostosis, in 1
with ulnar agenesis, and in 1 with multiple enchondromatosis. Patients underwent
distraction osteogenesis through either a unifocal or bifocal corticotomy.
Forearm length increased on average 6.0 cm (range, 3.6-8.1 cm) or 54% (range, 21%
to 94%) with a lengthening index of 1.3 months per centimeter (range, 0.6-1.9
months per centimeter). The length of follow-up averaged 4.5 years and involved
office examinations with task evaluation and a questionnaire addressing function
and appearance. Limb length discrepancy at follow-up measured 3.7 cm (range, 0.0
8.0 cm). Lengthening of the forearm was found to improve upper extremity
function; it allowed the patient to reach distant body parts and to perform
select activities requiring near-equal arm length. Forearm lengthening also
improved the appearance of the arm if adequate soft tissue was preserved. Full
restoration of arm length was not a requirement for a successful outcome and
patient satisfaction with the results of the procedure was high.
PMID- 10194020
TI - Evidence for a polyclonal etiology of palmar fibromatosis.
AB - X chromosome inactivation patterns at the androgen receptor locus were evaluated
to determine clonality in microdissected lesional tissue and in leukocytes from 2
women with Dupuytren's disease. The tissue from both patients generated a
polyclonal pattern of X chromosome inactivation of the human androgen receptor
gene. This finding supports a polyclonal reactive process as the underlying
etiology for palmar fibromatosis.
PMID- 10194021
TI - Fingertip reconstruction with flaps and nail bed grafts.
AB - We retrospectively reviewed the cases of 14 fingertips reconstructed with a
combination of local or regional flaps and nail bed grafts, some of which were
placed wholly or partially over a de-epithelialized flap. Most of the fingertips
sustained a crushing injury and were reconstructed at the time of the injury.
Soft tissue coverage was provided by palmar V-Y flaps in 6 cases, thenar flaps in
4, lateral V-Y flaps in 2, a Moberg flap in 1, and a cross-finger flap in 1.
Split toenail bed grafts were used in 6 cases, full-thickness nail bed grafts
from the amputated part in 6, and split nail bed grafts from the injured digit in
2. There was 1 partial graft loss and 1 partial flap loss. The remaining cases
had completely successful grafts and good soft tissue healing. Subsequent nail
growth and adherence were good in all but the 1 digit requiring secondary
composite grafting.
PMID- 10194022
TI - Upper extremity salvage using the tensor fascia lata flap: report of two cases.
AB - The tensor fascia lata pedicled flap was successfully used to salvage 3 severely
injured upper extremities in 2 patients. Both patients had undergone 3 prior free
tissue transfers without complete closure of their wounds. All 3 tensor fascia
lata flaps (2 myocutaneous, 1 myofascial) survived entirely. We believe this flap
offers a distinct advantage compared with the groin flap when pedicled flap
coverage of the upper extremity is required.
PMID- 10194023
TI - The anconeus muscle flap: its anatomy and clinical application.
AB - The arterial anatomy, coverage area, and potential donor site morbidity of the
anconeus muscle flap are described. Using 17 cadaveric upper extremities, we
investigated the muscle's arterial anatomy in 12 specimens and defined the
coverage area of the anconeus flap in 5 specimens. We also reviewed the records
of 9 patients who underwent a pedicle anconeus muscle flap for elbow coverage to
assess clinical results of the procedure. The anconeus muscle is supplied from 3
arterial pedicles: the recurrent posterior interosseus artery, the medial
collateral artery, and the posterior branch of the radial collateral artery. The
recurrent posterior interosseus artery and the medial collateral artery were
present in all dissected cadavers and consistently anastomosed with each other
underneath the anconeus muscle. By harvesting the muscle on the medial collateral
artery, the anconeus muscle flap can be expected to cover a 7.3 cm2 defect over
the radiocapitellar joint, a 6.1 cm2 defect over the distal triceps tendon, and a
7.2 cm2 defect over the olecranon. In this series, none of the patients
experienced loss of elbow motion, stability, or extension strength. The results
of this study indicate that the anconeus can be harvested with minimal risk of
morbidity and provides effective coverage for soft tissue defects of the elbow.
PMID- 10194024
TI - Early "simple" release of posttraumatic elbow contracture associated with
heterotopic ossification.
AB - "Simple" elbow release in the setting of heterotopic ossification is defined as
excision of ectopic bone and removal of restricting soft tissues without
associated articular procedures. In the past, such procedures were postponed
until bone scans were quiescent, serum alkaline phosphatase was normal, and the
ectopic bone was mature. Postoperative management sometimes included radiation
therapy, prolonged nonsteroidal anti-inflammatory agents, and intensive
physiotherapy. We believe that delayed treatment beyond the time of fracture
healing is unnecessary to obtain results comparable to those of previous studies.
Similarly, we propose that radiation therapy is not necessary after excision of
heterotopic ossification. Fourteen patients (15 elbows) were prospectively
managed with early excision of posttraumatic heterotopic ossification, immediate
postoperative mobilization, and a 5-day course of indomethacin. The average time
from injury to release was 23 weeks. The mean preoperative arc of
flexion/extension was 43 degrees; that of pronation/supination was 79 degrees.
After 2 years, the corresponding values were 120 degrees and 152 degrees. Cubital
tunnel syndrome, present in 5 patients, resolved after surgery. Three
postoperative complications occurred in 2 patients. There were no recurrent
contractures or loss of motion.
PMID- 10194025
TI - Snapping of the triceps tendon over the lateral epicondyle.
AB - We present a patient with translocation (snapping) of a portion of the triceps
over the lateral epicondyle with elbow flexion. This condition is in many ways
analogous to its counterpart at the medial aspect of the elbow, snapping of the
medial head of the triceps, a clinical entity that is being increasingly
recognized.
PMID- 10194026
TI - Pigmented villonodular synovitis of the elbow: a case report and literature
review.
AB - Pigmented villonodular synovitis is a well-described, benign proliferative
disorder of the synovium that rarely affects the elbow joint. Only 12 cases have
been reported in this site. A case is presented of elbow involvement by pigmented
villonodular synovitis that was documented by magnetic resonance imaging before
surgery and monitored until recurrence.
PMID- 10194027
TI - Innervation density of the base of the palm.
AB - Cutaneous nerves of the palm were localized and quantitated by longitudinal axis,
proximity to the distal palmar crease, and tissue layer to identify an incision
that would avoid injury to the palmar branches of cutaneous nerves. Cadaveric
palms (n = 10) harvested en bloc were fixed at physiologic tension and prepared
using the celloidin method and hematoxylin-eosin staining. The cutaneous nerves
of the palm were counted and classified by their size and location within each
tissue layer and longitudinal axis as well as by proximal, middle, and distal
locations within each axis. The mean number of large nerves identified within
regions of the palm differed by tissue layer and longitudinal axis but not by
longitudinal location within axes. The long/ring finger web space was
characterized by the lowest innervation density; the index/long finger web space
and ring finger axis were characterized by the greatest innervation density. An
incision in the long/ring finger web space 2 cm proximal to Kaplan's cardinal
line should result in injury to fewer nerves and reduce the incidence of painful
neuromas during open carpal tunnel release.
PMID- 10194028
TI - Symptoms, disability, and quality of life in patients with carpal tunnel
syndrome.
AB - We used validated outcome instruments to measure symptoms, disability, and health
related quality of life in 58 patients with carpal tunnel syndrome (CTS). The
patients completed the CTS instrument before and 6 weeks, 3 months, and 6 months
after surgery and the Short Form-36 (SF-36) before and 3 months after surgery.
The size of clinical change detected by each outcome measure was estimated by the
standardized response mean (mean change/ standard deviation of the change). Large
improvement was observed for the CTS symptom scale (mean standardized response,
1.4-1.9) and function scale (0.8-1.1). Improvement in SF-36 scales was large for
pain (1.0) and moderate for physical role, mental health, and the physical
component summary (0.5-0.6). Compared with the general population SF-36 norms (n
= 2,181), CTS patients had significantly worse scores for physical functioning,
physical role, pain, vitality, and the physical component summary before surgery.
After surgery, SF-36 scores had normalized except for physical role and the
physical component summary.
PMID- 10194029
TI - Recurrent aneurysmal bone cyst of the proximal phalanx treated with cryosurgery:
a case report.
AB - A recurrent aneurysmal bone cyst of the proximal phalanx treated with curettage,
cryosurgery, and bone grafting is presented. There is no evidence of recurrence
after 5 years. Although cryosurgery is commonly used as an adjuvant for
intralesional treatment for aneurysmal bone cyst, there have been no reports of
its use for the treatment of a lesion arising in the hand.
PMID- 10194030
TI - Pacinian neurofibroma of the hand: a case report and literature review.
AB - Pacinian neurofibroma is a rare, benign tumor not associated with von
Recklinghausen's disease (neurofibromatosis). Histologically, it is composed of a
proliferation of structures resembling normal pressure receptors. A case of
pacinian neurofibroma of the hand in a 4-year-old child is presented, along with
a review of the literature.
PMID- 10194031
TI - Small cell osteosarcoma of the ulna: a case report and review of the literature.
AB - We report a case of small cell osteosarcoma arising in the distal ulna. The
radiologic and pathologic features of this histologic variant of osteosarcoma
that allow differentiation from other lytic lesions with small round cells are
discussed.
PMID- 10194032
TI - Salvage by volume reduction of chronic allograft rejection in emphysema.
AB - BACKGROUND: We hypothesized that native lung volume reduction surgery (LVRS)
would improve respiratory function in patients who had previously undergone
single lung transplantation for emphysema and who were disabled by obliterative
bronchiolitis. METHODS: Seven single lung transplant recipients who had advanced
bronchiolitis obliterans syndrome (BOS grade 3b), absence of active infection,
and suitable anatomy underwent native LVRS. Mean time from lung transplantation
to LVRS was 39 +/- 17 months. RESULTS: Mean FEV1 rose from 684 +/- 164 ml before
LVRS to 949 +/- 219 ml at 3 months after LVRS, an increment of 40% (p = .002).
Mean 6-minute walk rose from 781 +/- 526 ft before LVRS to 887 +/- 539 ft at 3
months after LVRS (p = .031), and mean dyspnea index declined from 3.1 +/- 1.1
before LVRS to 1.6 +/- 0.5 at 3 months after LVRS (p = .010). Mean native lung
volume declined from 2956 +/- 648 ml before LVRS to 2541 +/- 621 ml at 3 months
after LVRS, but the change was not statistically significant (p = .12). Mean
transplant lung volume was little changed before and after LVRS (2099 +/- 411 ml
and 1931 +/- 607 ml, respectively, p = NS). There was also a trend toward
increased ventilation and perfusion of the native lung and reduction in
ventilation and perfusion of the transplant lung, but these changes did not
achieve statistical significance. By six months after LVRS, three patients died
(two as a consequence respiratory failure), and survivors began to show evidence
of deteriorating spirometry. CONCLUSIONS: LVRS is capable of salvaging
respiratory function in chronic allograft rejection in emphysema by reducing
native lung hyperinflation. These benefits, however, appear to be limited in
magnitude and duration by the severity of the underlying allograft dysfunction.
PMID- 10194033
TI - Maximal exercise capacity and peripheral skeletal muscle function following lung
transplantation.
AB - BACKGROUND: There have been many suggestions that diminished exercise capacity in
patients that have undergone lung transplantation is due, in part, to peripheral
muscle dysfunction, brought on by either detraining or immunosuppressive therapy.
There is limited data quantifying skeletal muscle function in this population,
especially in those more than 18 months post-procedure. The present study sought
to quantitate skeletal muscle function and cardiopulmonary responses to graded
exercise in 19 lung transplant recipients, 15 of which were mostly more than 18
months post-procedure. METHODS: Ten single- (SLT) and 9 double-lung
transplantation (DLT) underwent anthropometric measures and performed expiratory
spirometry, whole body plethysmography to assess lung volumes, static maximal
mouth pressures to assess respiratory muscle strength, progressive exercise
testing on a cycle ergometer (with cardiac output measurements being performed
every second workload) and isokinetic cycling to assess peripheral muscle power
and work capacity. RESULTS: The DLT group was younger than the SLT group (23.0
[21.0-32.0] vs 47.5 [43.0-55.0] median [interquartile range], p < .05) with no
differences in height, weight, or BMI. Despite the DLT group having significantly
better spirometric values (FEV1: 86% vs 56.5% median) and less airtrapping
(RV/TLC: 30% vs 53.5%), both groups were equally limited in exercise capacity
(Wmax)(38.0 percent predicted [30.0-65.0] vs 37.5 percent predicted [30.0-44.0],
SLT vs DLT), leg power (76.1 percent predicted [53.8-81.4] vs 69.0 percent
predicted [58.3-76.0]) and leg work capacity (63.3 percent predicted [34.7-66.8]
vs 38.4 percent predicted [27.5-57.3]). This lack of difference in performance
persisted when the analysis was limited to those more than 18 months post
procedure. Respiratory muscle strength was also not different for the two groups,
and was within normal limits. Wmax was best correlated with leg work capacity (r
= .84), but also with leg power, RV/TLC, FEV1 (r = .49, -.52, .58). When
normalized for age, height, and sex, percent predicted Wmax only correlated with
percent predicted leg work capacity (r = .58). Cardiac output was appropriate for
the work performed. CONCLUSIONS: We conclude that peripheral skeletal muscle work
capacity is reduced following lung transplantation and mostly responsible for the
limitation of exercise performance. While the causes of muscular dysfunction have
yet to be clarified, the preservation of respiratory muscle strength with the
concomitant reduction in leg power and work capacity suggests that most of the
muscular dysfunction post-transplantation is attributable to detraining.
PMID- 10194034
TI - The contribution of donor management and modified cold blood lung perfusate to
post-transplant lung function.
AB - BACKGROUND: Donor organ availability remains the major limiting factor in the
treatment of patients with end-stage lung disease by lung transplantation.
Maximising the use of available organs is therefore crucial. Details available at
the time of organ referral may give a misleading impression of their quality.
Intensive donor management may improve the quality of the organs thereby
improving the quality of the outcome. METHODS: We performed 56 heart-lung and 5
double lung transplants between November 1990 and September 1993; 49 had adequate
documentation for analysis. All organs were preserved with modified cold blood
solution with an ischemic time of 197 (117-297) minutes. Assessment of lung
function post-implantation was performed using an acute lung injury score as this
gives a more accurate indication of overall lung function. Donors were treated
intensively by bronchoscopy, optimal fluid management and appropriate lung
expansion. RESULTS: Careful management improved donor quality so that the
alveolar-arterial oxygen gradient fell significantly from 185 (+/-20) mmHg at
arrival to 80 (+/-11) mmHg (p < .0001) immediately prior to harvesting 190
minutes later. This improvement was maintained following harvesting using the
modified cold blood preservation solution so that lung injury was assessed as
"mild" according to the acute lung injury criteria post-transplantation. There
was one instance of primary lung failure following transplantation which was
neither related to the quality of the organ at harvesting nor to the method of
lung preservation. CONCLUSIONS: Intensive donor management significantly improves
the quality of donor organs, providing an improvement in immediate post
transplantation lung function. This improvement is maintained using modified cold
blood lung preservation solution.
PMID- 10194035
TI - Calcium channel blocker enhances lung preservation.
AB - BACKGROUND: The standard program for lung transplantation employs PGE1
pretreatment for donor lungs, but its efficacy remains controversial. Calcium
channel blocker has been reported more effective for reducing potassium-induced
vasoconstriction. We investigate the efficacy of calcium channel blocker in the
initial lung flush using rat lung transplant model. METHODS: The excised rat
lungs (n = 30) were flushed with either University of Wisconsin solution (UWS)
with a prior injection of 50 microg/kg PGE1 into the pulmonary artery (UWS +
PGE1; n = 7), UWS only (UWS; n = 7), or UWS containing 10(-6) M nifedipine (UWS +
Nif; n = 8). After storage (4 degrees C) for 24 hours, all lungs were reperfused
for 2 hours using an isolated, pulsatile blood perfused lung model. Control lungs
(n = 8) were reperfused immediately after harvest. Blood gas analysis and shunt
fraction, lung airway resistance, dynamic lung compliance, and pulmonary vascular
resistance were assessed. RESULTS: The pO2 at 30 minutes after reperfusion in the
control, UWS, UWS + PGE1, and UWS + Nif group were 88.0 +/- 3.2, 49.6 +/- 2.2,
52.0 +/- 2.4, 85.1 +/- 2.1 (mmHg), respectively. Until 30 minutes after
reperfusion, the pO2 in UWS and UWS + PGE1 group were significantly lower than
those in UWS + Nif group (p < .001). Shunt fraction, lung airway resistance, and
dynamic lung compliance also demonstrated the superiority of UWS + Nif group.
CONCLUSIONS: The early graft function after storage was significantly enhanced in
lungs flushed with UWS containing nifedipine. Calcium channel blocker is more
effective than PGE1 in reducing the potassium-induced vasoconstriction. Optimal
composition of the flush may require both calcium channel blocker for pulmonary
vasodilation and PGE1 for pulmonary protection by non-vasodilatory mechanisms.
PMID- 10194036
TI - Gas exchange function one month after transplantation of lungs topically cooled
for 2 hours in the non-heart-beating cadaver after failed resuscitation.
AB - BACKGROUND: If lungs from subjects dying of heart attacks could be used for
transplantation, the lung donor shortage could be radically reduced. The aim of
this study was to investigate, in an experimental survival model, the results of
lung transplantation using lungs from non-heart-beating donors. METHODS: The left
lung, topically cooled to 25 degrees C for 2 hours in situ after 5 minutes of
circulatory arrest and 26 minutes of unsuccessful cardiopulmonary resuscitation,
was transplanted into a syngeneic rat. Five weeks after the transplantation,
right pneumonectomy was performed and blood gases measured every 10 minutes for 1
hour. Comparison were made with two control groups, one where fresh donor lungs
were transplanted and another where only right pneumonectomy was done. RESULTS:
All animals survived and were in good condition at the end of the observation
period. There was no statistically significant difference in arterial oxygen or
carbon dioxide tension between the groups. The bronchial anastomoses showed
normal healing in all cases. CONCLUSION: Lungs from non-heart-beating donors
topically cooled in situ to 25 degrees C for 2 hours before being harvested
showed excellent gas exchange and bronchial healing 5 weeks after
transplantation.
PMID- 10194037
TI - Does PGE1 attenuate potassium-induced vasoconstriction in initial pulmonary
artery flush on lung preservation?
AB - The standard clinical protocol for lung transplantation employs cold single
pulmonary artery flush with Euro-Collins solution or the University of Wisconsin
solution. Prostaglandin E1 (PGE1) is usually given by direct injection into the
pulmonary artery to reduce pulmonary vasoconstriction caused by these
intracellular, high-potassium solutions, however, the efficacy of PGE1 on lung
preservation remains controversial. In this study we demonstrated that
vasodilator effects of PGE1 were markedly reduced under a high-potassium
condition, and that potassium-induced pulmonary vasoconstriction were inhibited
by calcium channel blocker nifedipine. There are three therapeutic options in the
cold single pulmonary artery flush for optimal lung transplantation, including
the use of a higher dose of PGE1, use of the calcium channel blocker instead of
PGE1, or the use of the extracellular, low-potassium solution such as low
potassium dextran solution for initial pulmonary artery flush before the lung
harvest.
PMID- 10194038
TI - Combination therapy with tacrolimus and mycophenolate mofetil following cardiac
transplantation: importance of mycophenolic acid therapeutic drug monitoring.
AB - BACKGROUND: Interest has recently been expressed in tacrolimus and mycophenolate
mofetil (MMF), two potent immunosuppressants, for a variety of transplant
indications. The efficacy of this combination was assessed as primary therapy
following cardiac transplantation. METHODS: Forty-five patients were enrolled; 15
into Phase I and 30 to Phase II of the study. Intravenous tacrolimus was
administered for 2-3 days to all patients prior to conversion to oral therapy;
target blood concentrations were 10-15 ng/mL. Treatment also consisted of
steroids and MMF. During Phase I, a fixed 2 g/day dose of MMF was given whilst
doses were adjusted according to mycophenolic acid (MPA) plasma levels during
Phase II (target range 2.5-4.5 microg/mL). Mean follow-up was 696 +/- 62 days and
436 +/- 88 days for Phases I and II, respectively. RESULTS: Phase I: Patient
survival was 100%. Rejection was diagnosed in 66.7% of patients (mean number of
episodes per patient 1.33 +/- 1.18). Retrospective analyses indicated that
whereas mean MPA plasma levels >3.0 microg/mL were not associated with rejection,
no correlation was found with tacrolimus blood concentrations. Phase II: A
survival rate of 96.7% was evident, one patient having died from aspergillosis.
Diagnoses of rejection were made in 10.0% of patients (0.10 +/- 0.31 episodes per
patient) and confounding factors were present in all 3 cases. MPA trough levels
were 1.0 +/- 0.3 microg/mL at this time. Resolution was apparent following pulse
steroid therapy. Steroids were successfully withdrawn from all patients who
completed 6 months' treatment. CONCLUSIONS: Combination therapy with tacrolimus
and MMF is associated with suppression of acute myocardial rejection; however,
this is dependent upon routine therapeutic drug monitoring.
PMID- 10194039
TI - Suppression of acute rejection in allogeneic rat lung transplantation: a study of
the efficacy and pharmacokinetics of rapamycin derivative (SDZ RAD) used alone
and in combination with a microemulsion formulation of cyclosporine.
AB - BACKGROUND: The novel immunosuppressant SDZ RAD, 40-0 (2-hydroxyethyl)rapamycin,
is an orally active rapamycin analogue developed for use in combination with
cyclosporine (Neoral). The present study was designed to evaluate the efficacy of
SDZ RAD, Neoral, or a combination of both drugs for suppression of acute
rejection in an allogeneic, unilateral rat lung transplant model. METHODS: Brown
Norway (RT1n) donor lungs were implanted into Lewis (RT1l) recipients that were
observed for 21 days. Postoperative evaluation included daily weights, serial
chest radiographs, drug trough levels, and histology scores of the transplanted
lung on the day of sacrifice. Treatment groups were comprised of rats treated
orally with the RAD vehicle as controls (n = 6); SDZ RAD 2.5 mg/kg/day (n = 9);
Neoral 7.5 mg/kg/day (n = 8); Neoral 2.5 mg/kg/day (n = 6); SDZ RAD 2.5 mg/kg/day
plus Neoral 7.5 mg/kg/day (n = 7); and Neoral 2.5 mg/kg/day plus SDZ RAD 2.5
mg/kg/day (n = 6). RESULTS: The results of this study showed that neither
monotherapy with 2.5 mg/kg/day of Neoral, nor 2.5 mg/kg/day of SDZ RAD prevented
severe acute rejection in unilateral lung transplant recipients. Furthermore,
despite high dose (7.5 mg/kg/day) Neoral treatment, graft histology showed
moderate rejection. However, addition of 2.5 mg/kg/day of SDZ RAD to 7.5
mg/kg/day of Neoral completely prevented histologic rejection in four of seven
grafts, although the remaining 3 grafts showed minimal rejection. This
combination resulted in significantly higher RAD trough levels when compared to
SDZ RAD treatment alone. Combining a lower dose of Neoral (2.5 mg/ kg/day) with
2.5 mg/kg/day of SDZ RAD resulted in less weight loss and improved animal health;
however, the histology of lung grafts in these rats showed mild rejection.
CONCLUSIONS: This is the first study on the efficacy of the novel rapamycin
derivative SDZ RAD for the control of acute lung allograft rejection. Results
showed that acute unilateral rat lung allograft rejection is refractory to
monotherapy with either high dose Neoral or SDZ RAD. The two regimens of combined
treatment with Neoral plus SDZ RAD used in these studies produced either minimal
rejection and reduced tolerability or mild rejection and better tolerability and
showed potentiation of immunosuppression when both drugs were used together.
Additional investigation of these two drugs is needed, however, to devise
regimens that produce both high immunosuppressive efficacy and good tolerability.
PMID- 10194040
TI - Avoidance of cellular blood product transfusions in LVAD recipients does not
prevent HLA allosensitization.
AB - BACKGROUND: Transfusion of cellular blood products during left ventricular assist
device (LVAD) implantation has been associated with HLA allosensitization,
resulting in the need for a negative prospective cross-match and prolonged
transplant waiting times. In order to prevent this risk, we developed a protocol
to avoid transfusion of cellular blood products. METHODS: The protocol included
preoperative patient stabilization, perioperative recombinant erythropoietin and
blood conservation strategies, and postoperative monitoring of mixed venous
oxygen saturation (SVO2) to assure adequate peripheral oxygen delivery. Panel
reactive antibody (PRA) was measured in all patients pre and post LVAD placement
to assess HLA sensitization. RESULTS: Seven consecutive patients underwent LVAD
implantation without transfusion of blood or platelets, one of whom expired
perioperatively. Mean hematocrit was 35.2% preoperatively, and 21.8%
postoperatively, reaching a nadir of 20.2%. Postoperative SVO2 was >60% in all
patients. In the six survivors, mean hematocrit reach 24.3%, 27.3%, and 33.0% by
postoperative day seven, fourteen, and thirty, respectively. PRA in three
patients was 0% preoperatively and remained 0% until transplantation after 33,
34, and 50 days of support. In two patients, preoperative PRA was 7% and 17%,
dropped to 3% and 0% after thirty days, then progressively rose to 96% and 100%
after 60 and 90 days, respectively. In one other patient, preoperative PRA was
0%, remained at 0% after thirty days, then rose to 96% by 60 days. CONCLUSIONS:
Avoiding transfusion of cellular blood products in LVAD recipients is safe and
well tolerated, but does not universally protect from HLA allosensitization.
Other factors may also produce sensitization, such as immunogenic components of
the LVAD, soluble antigen in fresh frozen plasma, or latent sensitization which
is not initially evident in critically ill and possibly anergic patients.
PMID- 10194041
TI - Development of a ventricular assist device for out-of-hospital use.
AB - BACKGROUND: Success with temporary ventricular assist devices, has prompted
interest in devices developed for long term use outside of the hospital setting.
METHODS: A totally implantable intrathoracic electro-hydraulic ventricular assist
device has been developed. Design focused on providing the recipient with a near
normal quality of life. To meet this goal the system utilizes transcutaneous
energy transfer and biotelemetry to eliminate percutaneous drive-lines/cables as
well as a displacement chamber capable of pressure equalization to atmospheric
pressures, so as to eliminate the need for percutaneous venting. An implanted
battery provides backup power to allow the recipient the ability to bathe,
shower, or swim without connection to an external power source. An integrated
telemedicine capability allows the device to be monitored/controlled remotely,
using telephone lines. RESULTS: The system has been tested in vitro with early
prototypes running for up to 5 1/2 years. The system was studied in calves (n =
25) with durations of support of up to 30 days, demonstrating the ability of the
device to function as a totally implantable device without percutaneous
connections. CONCLUSIONS: The various in vitro and in vivo studies have
demonstrated the feasibility of the totally implantable device. Chronic in vivo
experiments will follow in preparation for regulatory submissions for human use.
PMID- 10194043
TI - Summary measures: a superior method of data analysis in lung preservation
studies.
PMID- 10194042
TI - Cardiac troponin T is not a marker of biopsy-proven cellular rejection.
PMID- 10194044
TI - Diphtheria by donation?
PMID- 10194045
TI - Avoidance as a predictor of the biological course of HIV infection over a 7-year
period in gay men.
AB - The present study prospectively investigated the relation between avoidance
coping and active cognitive and behavioral coping and the progression of HIV
infection over 7 years in 181 gay men. Findings revealed that for a number of
medical and behavioral factors, (a) avoidance coping predicted a lower rate of
decline in CD4 cells, (b) the proportional hazard (PH) attributable to avoidance
of developing a syncytium-inducing HIV variant was 0.72 (95% confidence interval
[CI]: 0.53 - 0.99, p < .05), and (c) the PH attributable to avoidance of dropping
below 200 CD4 cells/microl was 0.66 (95% CI: 0.50 - 0.89, p < .01). Avoidance
coping was not related to the development of AIDS-defining clinical symptoms.
Active cognitive and behavioral coping was not related to the outcome measures.
PMID- 10194046
TI - Neurodevelopmental outcomes of Ugandan infants with HIV infection: an application
of growth curve analysis.
AB - Neurodevelopmental outcomes of human immunodeficiency virus Type 1 (HIV-1)
infected infants of non-drug-using mothers were assessed in a controlled,
prospective study from birth to 24 months with 3 groups: 61 infants of HIV
infected mothers, 234 uninfected infants of HIV-infected mothers (seroreverters),
and 115 uninfected infants of uninfected mothers. Compared with seroreverters and
uninfected infants, HIV-infected infants demonstrated lower mental and motor
development on the Bayley Scales and greater deceleration in their rate of motor
development. HIV-infected infants with abnormal neurologic exams had lower motor
and mental test scores and lower rates of motor Bayley Scales scores than their
HIV-infected counterparts with normal neurologic exams. Contrary to prediction,
no group differences in mean performance or growth rates were found on visual
information processing on the Fagan Test of Infant Intelligence.
PMID- 10194047
TI - Oral contraceptive use and hemodynamic, lipid, and fibrinogen responses to
smoking and stress in women.
AB - The effects of acute smoking and oral contraceptive (OC) use on cardiovascular,
lipid, and fibrinogen stress responses were examined in 52 female smokers and
nonsmokers, half of whom were using OCs. Women smoked or sham-smoked a cigarette
and then performed 2 stressful tasks. Stress elicited increases in total and low
density lipoprotein cholesterol, and in triglycerides among women who smoked, and
in fibrinogen among all women. Smokers who used OCs had greater blood pressure
increases to smoking and to stress than did smokers who did not use OCs. OC use
was also associated with enhanced total peripheral resistance stress responses
among women who smoked and cardiac output stress responses among women who sham
smoked. Results suggest that OC use moderates cardiovascular reactivity in
smokers but not nonsmokers, enhancing vascular responsivity to smoking combined
with stress and myocardial responsivity to stress alone.
PMID- 10194048
TI - Association of negative and positive social ties with fibrinogen levels in young
women.
AB - The associations between positive and negative aspects of social relationships
and fibrinogen, a risk factor for coronary heart disease (CHD), were examined in
young, healthy women recruited from the community (n = 46) and from a college
campus (n = 42). For community women, the perception that individuals in their
social networks frequently undermined them was related to higher fibrinogen,
independent of perceived frequency of support. For college women, fibrinogen was
elevated among women with frequent undermining only when they also reported
infrequent support. After controlling for other risk factors, the associations
between social ties and fibrinogen remained significant in both samples. These
results indicate that positive and negative social ties are associated with
fibrinogen levels and suggest that social relationships may affect CHD risk in
part through their influence on fibrinogen.
PMID- 10194049
TI - Modeling relationships among socioeconomic status, hostility, cardiovascular
reactivity, and left ventricular mass in African American and White children.
AB - In African American and White children and adolescents (N = 147), socioeconomic
status (SES) was measured in 2 ways: (a) using neighborhood-level measures of
population density, median income, educational attainment, and the number of
children born to single mothers and (b) using family-level measures of parents'
occupation and education. Structural equation modeling revealed that both lower
family SES and lower neighborhood SES were independently associated with greater
hostility and consequently greater cardiovascular reactivity to laboratory
stressors in African Americans. Independent of neighborhood SES, only lower
family SES was associated with greater cardiovascular reactivity in Whites.
Heightened cardiovascular reactivity was associated with greater left ventricular
mass (LVM) in Whites and marginally greater LVM in African Americans. Results
suggest the importance of using multiple indicators of SES and confirm the
relationship between SES and LVM in African Americans and Whites, albeit through
different pathways.
PMID- 10194050
TI - Social comparison and adjustment to breast cancer: an experimental examination of
upward affiliation and downward evaluation.
AB - In a study designed to evaluate the divergence of social comparison activities
under health threat, breast cancer patients (n = 94) were assigned randomly to
listen to an audiotaped interview in which the target's psychological adjustment
and disease prognosis were manipulated to reflect good, poor, and unspecified
psychological and physical health status. Results supported hypotheses regarding
downward self-evaluative and upward affiliative comparison activity, as well as
predictions regarding the influences of comparison dimension. With regard to
desire for affiliation, participants demonstrated a greater desire for
information and emotional support from the well-adjusted target than from the
poorly adjusted target. Self-evaluation of adjustment and prognosis varied as a
function of target characteristics, although a pervasive tendency toward downward
comparison in self-evaluation also was noted.
PMID- 10194051
TI - Concerns about breast cancer and relations to psychosocial well-being in a
multiethnic sample of early-stage patients.
AB - Much work on psychosocial sequelae of breast cancer has been guided by the
assumption that body image and partner reaction issues are focal. In a tri-ethnic
sample of 223 women treated for early-stage breast cancer within the prior year,
the authors assessed a wider range of concerns and relations to well-being.
Strongest concerns were recurrence, pain, death, harm from adjuvant treatment,
and bills. Body-image concerns were moderate; concern about rejection was
minimal. Younger women had stronger sexual and partner-related concerns than
older women. Hispanic women had many stronger concerns and more disruption than
other women. Life and pain concerns and sexuality concerns contributed uniquely
to predicting emotional and psychosexual disruption; life and pain concerns and
rejection concerns contributed to predicting social disruption. In sum,
adaptation to breast cancer is a process bearing on several aspects of the
patient's life space.
PMID- 10194052
TI - Assessment of irrational health beliefs: relation to health practices and medical
regimen adherence.
AB - The purpose of the present research was to provide initial validation of the 20
item Irrational Health Belief Scale (IHBS). Study 1 included 392 undergraduate
psychology students. Results from Study 1 suggested that the IHBS total score is
internally consistent and stable over an 18-month time period. Greater health
related cognitive distortion (higher IHBS scores) was associated with weaker
internal health locus of control beliefs, lower positive affectivity, stronger
chance health locus of control beliefs, and greater negative affectivity. Most
important, greater cognitive distortion was uniquely and significantly associated
with a less positive pattern of health practices. Study 2 involved 107
individuals with Type I diabetes mellitus. Results indicated that higher IHBS
scores were significantly associated with both objective (hemoglobin HbA1) and
self-reported diabetic regimen adherence independent of trait neuroticism and
conscientiousness.
PMID- 10194053
TI - Temporomandibular disorders: evidence for significant overlap with
psychopathology.
AB - Data were analyzed for 277 acute and chronic temporomandibular disorder (TMD)
patients to determine if there was a relationship between psychological and
physical diagnoses. A significant (p < .01) relationship existed among the
following: combined past or current mood disorder-personality disorder and muscle
disorder; combined current mood, anxiety, or substance use disorder-personality
disorder and muscle disorder; and combined current anxiety disorder-personality
disorder and muscle disorder. This study further confirmed other research that
has found that significant psychopathology exists in TMD. More important, this
psychopathology appears to be linked primarily to muscle disorders, as opposed to
disc or joint disorders, within the rubric of TMD.
PMID- 10194054
TI - The patient exit interview as an assessment of physician-delivered smoking
intervention: a validation study.
AB - In evaluating the efficacy of physician-delivered counseling interventions for
health behavior changes such as smoking cessation, a major challenge is
determining the degree to which interventions are implemented by physicians. The
Patient Exit Interview (PEI; J. Ockene et al., 1991) is a brief measure of a
patient's perception of the content and quantity of smoking cessation
intervention received from his or her physician. One hundred eight current
smokers seen in a primary care clinic completed a PEI following their physician
visit. Participants were 45% male, 95% Caucasian, with a mean age of 42 years and
an average of 22 years of smoking. The PEI correlated well with a criterion
measure of an audiotape assessment of the physician-patient interaction (r = .67,
p < .001). When discrepancy occurred, in general it was due to patients' over
reporting of intervention as compared with the criterion measure. Implications
and limitations of these findings are discussed.
PMID- 10194055
TI - Message framing and sunscreen use: gain-framed messages motivate beach-goers.
AB - Prospect theory suggests that people respond differentially to factually
equivalent messages depending on how these messages are framed (A. Tversky & D.
Kahneman, 1981). A. J. Rothman and P. Salovey (1997) relied on prospect theory to
predict that messages highlighting potential "gains" should promote prevention
behaviors such as sunscreen use best. This experiment compared the effectiveness
of 4 differently framed messages (2 highlighting gains, 2 highlighting losses) to
persuade 217 beach-goers to obtain and use sunscreen. Attitudes and intentions
were measured before and immediately following the delivery of the framed
information, and after completing the questionnaire participants were given a
coupon redeemable for a small bottle of sunscreen later that same day. People who
read either of the 2 gain-framed brochures, compared with those who read either
of the 2 loss-framed brochures, were significantly more likely to (a) request
sunscreen, (b) intend to repeatedly apply sunscreen while at the beach, and (c)
intend to use sunscreen with a sun protection factor of 15 or higher.
PMID- 10194056
TI - Of needles and skinned knees: children's coping with medical procedures and minor
injuries for self and other.
AB - Children participated in four role-plays designed to assess what the children
themselves would do and what they would suggest a friend should do when
encountering a medical procedure and a minor injury. Open-ended responses were
coded into an empirically derived continuum suggested by past research. Similar
responses were given to cope with medical procedures and injuries. However,
children suggested more reactive coping strategies (e.g., cry, pull away) for
themselves and more proactive responses (e.g., think of something fun, take deep
breaths) for friends. This finding questions the assumption that children choose
the most effective coping strategy in their repertoire when they themselves
confront an aversive stimulus, suggesting that preparation for invasive
procedures should include motivational components.
PMID- 10194057
TI - Therapeutic implications of drug interactions in the treatment of human
immunodeficiency virus-related tuberculosis.
PMID- 10194058
TI - Proceedings of a symposium on molecular mechanisms of microbial host cell
interactions in periodontal disease. St Petersburg, Florida, USA. March 1997.
PMID- 10194059
TI - Pathogenic neisseriae: complexity of pathogen-host cell interplay.
AB - Recent studies have provided insight into the function of important neisserial
adhesins (pili and Opa) and their interaction with cellular receptors, including
members of heparan sulfate proteoglycan, CD66, and integrin receptor families.
These interactions not only allow colonization of the human mucosa but also
stimulate cellular signaling cascades involving phosphatidylcholine-dependent
phospholipase C, acidic sphingomyelinase and protein kinase C in epithelial
cells, and Src-related kinases, Rac1, p21-activated kinase, and Jun N-terminal
kinase in phagocytic cells. Activation of these pathways is essential for
cellular entry and intracellular accommodation of the pathogens but also leads to
early induction of cytokine release, thus priming the immune response. Detailed
knowledge of the cellular signaling cascades that are activated by infection will
aid us in applying both current and novel interfering drugs (in addition to
classical antibiotic therapy) as therapy and prophylaxis for persistent or
otherwise difficult-to-treat bacterial infections, including periodontal
infections.
PMID- 10194060
TI - Cystalysin, a 46-kDa L-cysteine desulfhydrase from Treponema denticola:
biochemical and biophysical characterization.
AB - A 46-kDa hemolytic protein referred to as cystalysin, from Treponema denticola
ATCC 35404, was characterized and overexpressed in Escherichia coli LC-67.
Cystalysin lysed erythrocytes, hemoxidized hemoglobin to sulfhemoglobin and
methemoglobin, and removed the sulfhydryl and amino group from selected S
containing compounds (e.g., cysteine) producing H2S, NH3, and pyruvate. With L
cysteine as substrate, cystalysin obeys Michaelis-Menten kinetics. Cystathionine
and s-aminoethyl-L-cysteine were also substrates. Several of the small alpha
amino acids were found to be competitive inhibitors of cystalysin. The enzymatic
activity was increased by beta-mercaptoethanol and was not inhibited by the
proteinase inhibitor TLCK (N alpha-p-tosyl-L-lysine chloromethyl ketone),
pronase, or proteinase K, suggesting the functional site was physically protected
or located in a small fragment of the polypeptide. We hypothesize that cystalysin
is a pyridoxal-5-phosphate-containing enzyme with the activity of an alphaC-N and
betaC-S lyase (cystathionase). Since high amounts of H2S have been reported in
deep periodontal pockets, this metabolic enzyme from T. denticola may also
function in vivo as an important virulence molecule.
PMID- 10194061
TI - Interactions between enteropathogenic Escherichia coli and epithelial cells.
AB - Enteropathogenic Escherichia coli (EPEC) may be considered a paradigm for a
multistage interaction between pathogen and host cell. EPEC strains produce a
type IV pilus that is associated with initial adherence to host cells, and these
strains possess a type III secretion apparatus that is necessary for transducing
signals to host cells. Secretion of three Esp proteins is required for activation
of a phosphotyrosine-containing receptor that allows EPEC to bind intimately to
host cells via the bacterial outer membrane protein intimin. Intimately attached
bacteria rest upon a pedestal composed of host cytoskeletal proteins in an
arrangement recognized as the attaching and effacing phenotype. The precise
molecular interactions that lead to these dramatic alterations in the host cell
cytoskeleton remain to be elucidated.
PMID- 10194062
TI - Role of gingipains R in the pathogenesis of Porphyromonas gingivalis-mediated
periodontal disease.
AB - It has been demonstrated that the Porphyromonas gingivalis cysteine proteinases
(gingipains) activate and/or degrade a broad range of host proteins. Inactivation
of gingipains R prior to infection of mice results in a decrease in the virulence
of P. gingivalis. Analysis of mouse, rabbit, and chicken antisera raised to
gingipain R1 demonstrated that the hemagglutinin domains of gingipains are very
immunogenic; however, immunization of mice with a peptide derived from the
hemagglutinin domain did not protect mice from P. gingivalis infection. Our
recent studies indicate that immunization of mice with a peptide corresponding to
the N-terminus of the catalytic domain of gingipains R results in the generation
of an immune response that affords protection of mice from P. gingivalis
infection. It is postulated that the protection observed results from the
inactivation of the enzymatic activity of gingipains R as a result of antibody
recognition of a processing site on the gingipain R precursor.
PMID- 10194063
TI - Rupture of the intestinal epithelial barrier and mucosal invasion by Shigella
flexneri.
AB - Invasion of the intestinal barrier by Shigella flexneri involves complex
interactions with epithelial and phagocytic cells. Major perturbation of the
signals that maintain epithelial integrity permits mucosal invasion, leading to
tissue destruction. Expression of this invasive phenotype depends on the
secretion of Ipa proteins (invasins), which can trigger entry of the pathogen
into epithelial cells by causing massive rearrangement of the host cell
cytoskeleton and cause macrophage apoptotic death by direct interaction of IpaB
with interleukin-1beta (IL-1beta)-converting enzyme. This results in the killing
of defense cells and in the release of IL-1beta. In vivo, bacteria translocate
through the epithelial barrier, essentially via M cells of the follicle
associated epithelium in the colonic and rectal mucosa. Apoptotic death of
macrophages in subepithelial tissues allows bacterial survival and triggers
inflammation, which destabilizes epithelial structures and facilitates further
bacterial entry. Once they are intracellular, bacteria multiply within the
cytoplasm and move from cell to cell by an actin-dependent process.
PMID- 10194064
TI - Endotoxin interactions with lipopolysaccharide-responsive cells.
AB - Recent work has identified two proteins that work together to enable many cell
types to respond to endotoxin. These two proteins, lipopolysaccharide (LPS)
binding protein (LBP) and CD14, also participate in cellular internalization of
endotoxin, which may occur independently of cellular activation. Current work
with antibodies to LBP and CD14 as well as "knockout" mice in the context of LPS
initiated endotoxic shock suggests that inhibition of this pathway could be
therapeutically useful. These observations point to the need to identify new
molecules that mediate LPS-initiated transmembrane signaling and internalization
of LPS-protein complexes.
PMID- 10194065
TI - The potential role of chemokines and inflammatory cytokines in periodontal
disease progression.
AB - Inflammation is regulated by the expression of mediators that cause a number of
pleiotropic events culminating in the recruitment of inflammatory cells and
release of biologic mediators by leukocytes. If the inflammation is transient in
nature, it can protect the host by activating defense mechanisms and initiating
wound repair. However, if the inflammation is inappropriate, it can lead to
considerable tissue damage. My colleagues and I have investigated the role of
chemokines, particularly monocyte chemoattractant protein 1, in various
pathological processes and the role of the proinflammatory cytokines interleukin
1 (IL-1) and tumor necrosis factor (TNF) in experimental periodontitis. I will
discuss first the studies on chemokines and then the use of IL-1 and TNF blockers
in inhibiting inflammation and bone loss in the periodontium.
PMID- 10194066
TI - Lipopolysaccharide structure influences the macrophage response via CD14
independent and CD14-dependent pathways.
AB - CD14, a protein expressed on the surface of monocytes and neutrophils, is a major
receptor for lipopolysaccharide (LPS). Studies with normal and CD14-deficient
macrophages show that responses to low concentrations of LPS require expression
of CD14, whereas responses to high concentrations of LPS are CD14-independent.
Since LPS isolated from different bacterial species shows structural variability,
studies were performed to determine whether differences in LPS structure
influence CD14-dependent and CD14-independent responses. Studies with LPS
purified from Escherichia coli, Salmonella abortus subspecies equi, Salmonella
minnesota, Pseudomonas aeruginosa, Neisseria meningitidis, Bacteroides fragilis,
and Rhodobacter sphaeroides show that the strongest CD14-dependent responses
require a typical O-antigen, long carbohydrate chains, at least 6 acyl chains in
their lipid A, and 2-phosphorylated Kdo moieties; wild-type LPS lacking a typical
O-antigen and containing short carbohydrate chains and 2-phosphorylated Kdo
moieties induces the strongest CD14-independent response.
PMID- 10194067
TI - Escherichia coli and Porphyromonas gingivalis lipopolysaccharide interactions
with CD14: implications for myeloid and nonmyeloid cell activation.
AB - Porphyromonas gingivalis, a gram-negative bacterium, is an etiologic agent for
adult periodontitis. Lipopolysaccharide (LPS) released from this bacterium can
react with numerous host cell types. P. gingivalis LPS stimulates tumor necrosis
factor alpha and interleukin-1beta secretion from monocytes (myeloid) but does
not elicit E-selectin expression from human endothelial cells (nonmyeloid). In
contrast, Escherichia coli LPS facilitates expression of these inflammatory
mediators through CD14-dependent pathways on both myeloid and nonmyeloid cells.
LPS binding studies have revealed that although P. gingivalis and E. coli LPSs
bind to CD14 differently, this fact does not adequately explain the lack of
endothelial cell activation by P. gingivalis LPS. Rather, LPS binding site and
blocking monoclonal antibody epitope mapping studies have suggested that CD14
presents a charged surface that captures different microbial ligands by
electrostatic interactions. We propose that human endothelial cells do not
respond to P. gingivalis LPS because of their inability to "recognize" CD14-P.
gingivalis LPS complexes.
PMID- 10194068
TI - Induction of prostaglandin release from macrophages by bacterial endotoxin.
AB - This review summarizes the role of the monocytic responses to lipopolysaccharide
as it relates to periodontal disease severity. Data are presented which
illustrate that the levels of prostaglandin E2 (PGE2) secreted by systemic
peripheral blood monocytes in culture, in the presence of bacterial endotoxins,
are highly correlated with the levels observed in the gingival crevicular fluid.
Furthermore, the different periodontal diagnostic categories have varying levels
of monocytic and crevicular fluid PGE2, in juxtaposition with clinical disease
severity. These data are consistent with the concept that there is close
synchrony between the systemic responsiveness of peripheral blood monocytes with
regard to prostanoid synthesis and the local levels of mediator present within
the gingival crevice.
PMID- 10194069
TI - Differential tumor necrosis factor alpha production in simian immunodeficiency
virus-infected rhesus macaques coinfected with Mycobacterium avium.
AB - Mycobacterium avium infections are the third most common opportunistic infection
in patients with AIDS. Simian immunodeficiency virus (SIV)-infected rhesus
macaques naturally acquire M. avium infections from the environment, and their
clinical symptoms are similar to those observed in AIDS patients. We
characterized concurrent infection with SIV and M. avium in monkeys on the basis
of the growth of the bacteria in macrophages (Mphis) from rhesus macaques and the
ability of M. avium to induce SIV replication and tumor necrosis factor alpha
(TNF-alpha) production. The simian M. avium isolate grew significantly better
than did an isolate from an AIDS patient or a chicken isolate (P = .001); it
induced significantly more TNF-alpha production in Mphis from SIV-positive and
SIV-negative monkeys than did the isolate from an AIDS patient (P = .013). No
significant increase in SIV replication was seen in the M. avium isolates, and no
correlation was found between increased SIV replication and increased TNF-alpha
production. In addition, Mphis from monkeys infected with M. avium during late
stage SIV disease produced less TNF-alpha when stimulated with virulent M. avium.
PMID- 10194070
TI - Host modulation as a therapeutic strategy in the treatment of periodontal
disease.
AB - Specific microorganisms initiate the immunoinflammatory processes that destroy
tissue in periodontitis. Recent work has demonstrated, in addition to bacterial
control, that modulation of the host immunoinflammatory response is also capable
of controlling periodontitis. Matrix metalloproteinases (MMPs) destroy collagen
and other matrix components, and the osteoclastic bone remodeling determines the
periodontal bone response to a bacterial challenge. Other components of the
biology, including cytokines and prostanoids, regulate MMPs and bone remodeling
and are also involved in regulating the production of defensive elements, such as
antibody. Agents directed at blocking MMPs or osteoclastic activity are effective
in reducing periodontitis. Agents that inhibit prostaglandin E2 and selective
blockage of specific cytokines have also been effective. Improved knowledge of
bacterium-host interactions and of the processes leading to tissue destruction
will help to identify targets for host modulation to reduce periodontitis in
selected situations.
PMID- 10194071
TI - Photo quiz. HIV seroconversion illness.
PMID- 10194072
TI - Phase I study of combination therapy with intravenous cidofovir and oral
ganciclovir for cytomegalovirus retinitis in patients with AIDS.
AB - Ganciclovir and cidofovir, two antiviral agents used in the treatment of
cytomegalovirus (CMV) retinitis, have a synergistic effect inhibiting CMV
replication in vitro. In a phase I study, seven patients with AIDS-related CMV
retinitis were treated with cidofovir (5 mg/kg intravenously every 2 weeks)
combined with ganciclovir (1 g orally three times a day). During a median of 5.5
months (range, 1-12 months) of combined therapy, only one patient had retinitis
progression, and only two of 28 blood cultures (specimens of which were obtained
on a monthly basis) yielded CMV. Dose-limiting adverse ocular effects (anterior
uveitis [two patients] and hypotony [two patients]) occurred in three of seven
patients. The results suggest that combination therapy with intravenous cidofovir
and oral ganciclovir (a regimen that does not require indwelling central venous
catheter access) might enhance clinical efficacy. Less frequent administration of
cidofovir in combination with oral ganciclovir should be prospectively studied to
determine if the incidence of treatment-associated toxicity might be reduced.
PMID- 10194073
TI - Cytomegalovirus retinitis in persons with AIDS--a shift in the treatment
paradigm?
PMID- 10194074
TI - A high prevalence of serum GB virus C/hepatitis G virus RNA in children with and
without liver disease.
AB - The role of GB virus C/hepatitis G virus (GBV-C/HGV) in adult and pediatric liver
disease is unclear. We detected serum GBV-C/HGV RNA by reverse transcriptase
polymerase chain reaction in 1 (3%) of 38 cholestatic infants, in 4 (4%) of 95
children without liver disease, and in none of 30 children with autoimmune
hepatitis. One cholestatic infant had antibodies, presumably maternal, to GBV
C/HGV. Sequence analysis of a nonstructural 3 region fragment suggested that
mother-to-infant transmission was the route of infection for the cholestatic
infant. The four infected children without liver disease had normal liver
function test results and lacked risk factors for bloodborne infections. Thus,
the detection of GBV-C/HGV RNA among children with and without liver disease
suggests that chronic GBV-C/ HGV infections may be established early in life,
possibly by mother-to-infant transmission. This may explain in part the high
prevalence of serum GBV-C/HGV RNA and antibodies in healthy adults.
PMID- 10194075
TI - Influenza vaccination of human immunodeficiency virus (HIV)-infected adults:
impact on plasma levels of HIV type 1 RNA and determinants of antibody response.
AB - We assessed the effect of influenza vaccination on plasma levels of human
immunodeficiency virus type 1 (HIV-1) RNA and the impact of age, plasma HIV-1 RNA
level, CD4 cell count, and anti-HIV therapy on immune response. Forty-nine adults
(mean age, 38.7 years; mean CD4 cell count +/- SD, 190 +/- 169/mL; mean plasma
HIV-1 RNA level +/- SD, 154,616 +/- 317,192 copies/mL) were immunized. Elevations
of > or = 0.48 log in plasma HIV-1 RNA levels occurred in two (4%) of 49 subjects
within 4 weeks of vaccination. A fourfold or greater increase in antibody titer
occurred in 13 (45%) of 29 subjects, correlating directly with CD4 cell count (P
= .002) and inversely with plasma HIV-1 RNA level (P = .034). By multivariate
analysis, CD4 cell count was a stronger predictor of antibody response than was
plasma HIV-1 RNA level. We conclude that increases in plasma HIV-1 RNA levels
following influenza vaccination are rare and transient and that antibody response
is impaired with CD4 cell counts of < 100/mL and plasma HIV-1 RNA levels of >
100,000 copies/mL. Prospective trials are needed to evaluate the impact of highly
active therapy on immune response after vaccination.
PMID- 10194076
TI - Influenza, influenza virus vaccine, and human immunodeficiency virus infection.
PMID- 10194077
TI - Serum IgG antibody responses to pertussis toxin and filamentous hemagglutinin in
nonvaccinated and vaccinated children and adults with pertussis.
AB - Levels of IgG antibody to pertussis toxin (PT) and filamentous hemagglutinin
(FHA) were measured in paired serum samples from 781 patients fulfilling at least
one laboratory criterion for pertussis that was suggested by an ad hoc committee
sponsored by the World Health Organization. The patients were participants or
family members of participants in a double-blind efficacy trial of a
monocomponent pertussis toxoid vaccine. Of 596 nonvaccinated children, 90% had
significant (two-fold or more) rises in PT IgG and FHA IgG levels. Only 17 (32%)
of 53 children previously vaccinated with three doses of pertussis toxoid had
rises in PT IgG levels because they already had elevated PT IgG levels in their
acute-phase serum samples. PT IgG and FHA IgG levels were significantly higher in
acute-phase serum samples from 29 adults than in acute-phase serum samples from
the nonvaccinated children. Nevertheless, significant rises in levels of PT IgG
(79% of samples) and FHA IgG (90%) were demonstrated in adults. In conclusion,
assay of PT IgG and FHA IgG in paired serum samples is highly sensitive for
diagnosing pertussis in nonvaccinated individuals. Assay of PT IgG levels in
paired sera is significantly less sensitive for diagnosis of pertussis for
children vaccinated with pertussis toxoid.
PMID- 10194078
TI - Serum IgG antibody response to pertussis toxin in persons for whom pertussis
vaccination failed depends upon the number of antigens in the vaccine.
PMID- 10194079
TI - Human herpesvirus 6 DNA in cerebrospinal fluid specimens from allogeneic bone
marrow transplant patients: does it have clinical significance?
AB - Cerebrospinal fluid (CSF) specimens from 22 allogeneic bone marrow transplant
patients with central nervous system (CNS) symptoms (cases) and 107 patients who
were immunocompromised but did not have CNS symptoms (controls) were assayed for
human herpesvirus 6 (HHV-6) DNA. HHV-6 DNA was detected in CSF specimens from
five (23%) of 22 cases and in CSF specimens from one (0.9%) of 107 controls (P <
.001, Fisher's exact test). In addition, none of the five cases with HHV-6 DNA
detected in CSF samples had any other identified cause of their CNS symptoms, and
none of the other 11 cases with known causes for their CNS diseases had HHV-6 DNA
detected in CSF samples (P = .03, Fisher's exact test). In three cases, HHV-6
variant B was identified, and the HHV-6 variant could not be defined in the other
two cases. Prophylaxis with acyclovir did not prevent the occurrence of HHV-6
associated CNS disease after allogeneic bone marrow transplantation. Four cases'
conditions were improved or they were cured after treatment with either
ganciclovir or foscarnet, and one case died of CNS disease despite foscarnet
treatment.
PMID- 10194080
TI - Successful oral doxycycline treatment of Lyme disease-associated facial palsy and
meningitis.
AB - Twenty-nine patients, aged 11-79 years (mean, 50 years), with Lyme
neuroborreliosis, facial nerve palsy, and meningitis were treated with oral
doxycycline (daily dose, 200-400 mg) for 9-17 days in a prospective,
nonrandomized study. Facial paresis was bilateral in eight (28%) of the 29
patients. Twenty-six patients (90%) recovered without sequelae within 6 months,
while three of the patients with bilateral facial palsy at admission had
remaining paresis at follow-up. In five patients, contralateral facial paresis
developed 1-12 days after initiation of therapy, and two patients were retreated
with antibiotics. Posttreatment examinations of cerebrospinal fluid showed a
marked decrease of inflammatory cells and protein concentrations compared with
pretreatment levels in all followed up patients. The favorable clinical outcome
agrees with findings of other reports on intravenous antibiotic therapy for Lyme
disease-associated meningitis with facial palsy. Our conclusion is that oral
doxycycline is an effective and convenient therapy for Lyme disease-associated
facial palsy.
PMID- 10194081
TI - Incidence and risk factors of toxoplasmosis in a cohort of human immunodeficiency
virus-infected patients: 1988-1995. HEMOCO and SEROCO Study Groups.
AB - The incidence of cerebral and extracerebral toxoplasmosis among 1,699 HIV
infected patients followed in the SEROCO and HEMOCO cohorts (1988-1995) was
studied. It increased from 0.7 per 100 person-years in 1988 to 2.1 per 100 person
years in 1992, as a result of the increasing prevalence of patients with CD4 cell
counts below 200/microL. It decreased thereafter to 0.2 per 100 person-years in
1995, while the proportion of patients receiving specific prophylaxis was
increasing. A Toxoplasma antibody titer of >150 IU/mL was an important predictor
of toxoplasmosis (adjusted relative risk [aRR], 3.6 [95% confidence interval, 2.1
6.0]), independent of a CD4+ cell count of <200/microL (aRR, 20.8) and specific
prophylaxis (aRR, 0.2 [0.1-0.3]). The median CD4+ cell count was 389/microL at
the time the antibody titer was first noted to be >150 IU/mL, while the median
CD4 cell count at onset of toxoplasmosis was 58/microL. Thus, disease was
diagnosed 10 days to 74 months after the rise in Toxoplasma antibody titers.
While the risk factors for development of toxoplasmosis remain incompletely
defined, the importance of specific prophylaxis for patients with low CD4 cell
counts and high Toxoplasma antibody titers is supported by these findings.
PMID- 10194082
TI - Relative bradycardia is not a feature of enteric fever in children.
AB - We investigated pulse-temperature relationships in 66 children with enteric fever
(group 1) and in 76 with other infections (group 2). Group 1 children were older
than group 2 children (mean age +/- SD, 91 +/- 36 vs. 66 +/- 32 months,
respectively; P < .001) and had mean oral temperatures +/- SD similar to those of
group 2 children (38.3 +/- 1.0 vs. 38.3 +/- 0.9 degrees C, respectively; P > .2);
however, group 1 children had lower mean baseline pulse rates +/- SD than did
group 2 children (119 +/- 25 vs. 127 +/- 28 beats/min, respectively; P < .001).
In a multiple linear regression model, pulse rate was independently associated
with age (inversely; P < .001) and oral temperature (positively; P < .006) but
not with diagnostic group or gender (P > .5). After adjustment of the mean
initial pulse rate +/- SD to age of 72 months, there was no difference between
group 1 and group 2 children (126 +/- 24 vs. 126 +/- 20 beats/min, respectively;
P > .5). From 4 to 72 hours after commencement of treatment, the mean oral
temperature in group 1 patients was approximately 0.3 degrees C higher than that
in group 2 patients, and the age-adjusted pulse rate was 5 beats/min higher in
group 1 children than in group 2 children. These data suggest that relative
bradycardia is not characteristic of enteric fever in children.
PMID- 10194083
TI - Assessment of therapeutic response of oropharyngeal and esophageal candidiasis in
AIDS with use of a new clinical scoring system: studies with D0870.
AB - We developed and compared five scoring systems designed to quantitate therapeutic
response in cases of oropharyngeal candidiasis. We utilized prospectively
collected data on 114 patients treated with several doses of the azole D0870.
Patients were infected with fluconazole-susceptible (n = 49) or -resistant
organisms (MIC, > or = 16 mg/mL; n = 61). Patients with fluconazole resistance
had lower CD4+ cell counts at baseline; more symptoms (P = .0006); a higher
frequency of dysgeusia (P = .004), dysphagia (P = .006), and throat pain (P =
.0034); and greater oral coverage by plaques of Candida. There was no difference
between the two groups in terms of colony-forming units, and any change did not
correlate with response to therapy. Resolution of dysphagia (P < .01) and oral
pain (P < .01) correlated well with response to therapy, unlike retrosternal pain
and throat pain, which were also less frequent. Xerostomia, a "furry" taste, and
dysgeusia were frequent nonspecific symptoms. Scoring system C, weighting
resolution of a symptom higher than absence of a symptom at baseline, yielded the
best correlation with global outcome (r = 0.86) and allows the quantitation of
incomplete but clinically beneficial responses to therapy.
PMID- 10194084
TI - Artemether for severe malaria: a meta-analysis of randomized clinical trials.
AB - The treatment of choice for severe malaria is quinine. However, a gradual
progression of resistance to quinine has become a concern in parts of the world.
Artemisinin-related compounds are a relatively new class of drugs. This meta
analysis assesses the evidence regarding the clinical effectiveness of artemether
for severe malaria. Computerized literature searches identified all randomized
clinical trials of artemether in comparison with quinine. Standardized data
extraction was independently performed by both authors. Results of nine trials,
entered in the meta-analysis, demonstrate the absence of a significant difference
between artemether and quinine in terms of mortality rate (odds ratio [OR], 0.76;
95% confidence interval [CI], 0.50-1.14). Statistical pooling of data from trials
in Southeast Asia showed a trend toward enhanced reduction of mortality (OR,
0.38; 95% CI, 0.14-1.02). These data demonstrate the equality of artemether and
quinine for severe malaria and indicate a trend toward greater effectiveness of
artemether in regions where there is recognized quinine resistance.
PMID- 10194085
TI - Evidence of efficacy of the Lederle/Takeda acellular pertussis component
diphtheria and tetanus toxoids and pertussis vaccine but not the Lederle whole
cell component diphtheria and tetanus toxoids and pertussis vaccine against
Bordetella parapertussis infection.
AB - A subanalysis of a recent cohort efficacy trial of a pertussis vaccine was
performed to determine its efficacy against cough illnesses due to Bordetella
parapertussis infections. Infants received four doses of either the
Lederle/Takeda acellular pertussis component diphtheria and tetanus toxoids and
pertussis (DTaP) vaccine or the Lederle whole-cell component diphtheria and
tetanus toxoids and pertussis (DTP) vaccine at 3, 4.5, 6, and 15-18 months of
age; controls received three doses of diphtheria and tetanus toxoids (DT) vaccine
only. All subjects were prospectively followed for cough illnesses of > or = 7
days' duration; cases of B. parapertussis infection were confirmed by positive
culture, household contact, or serology. Seventy-six cough illnesses due to B.
parapertussis were identified; 24 occurred in 929 DTaP recipients, 37 in 937 DTP
recipients, and 15 in 321 DT recipients, resulting in an efficacy of 50% for DTaP
vaccine (95% CI [confidence interval], 5% to 74%) and 21% for DTP vaccine (95%
CI, -45% to 56%). The data in the present analysis suggest that the
Lederle/Takeda DTaP vaccine but not the Lederle whole-cell component DTP vaccine
has efficacy against B. parapertussis infection.
PMID- 10194086
TI - Molecular epidemiology of gram-negative bacteremia.
AB - We did pulsed field gel electrophoresis (PFGE) and antibiotic susceptibility
testing on 202 gram-negative isolates obtained from blood cultures between 1
January 1989 and 31 December 1993. Seventy-eight patients had at least two gram
negative isolates of the same species recovered from blood drawn one or more days
apart and met the other study criteria. Twenty patients had only 1 bloodstream
infection, 48 patients had 1 recurrence of bacteremia, and 10 patients had > 1
recurrence of bacteremia. Of 80 recurrences of bacteremia, 52 (65%) were relapses
and 28 (35%) were reinfections. Seventy-eight percent of the episodes of
bacteremia occurring < or = 300 days apart were relapses, and 100% occurring >
300 days apart were reinfections (P < .001). Organisms causing recurrent
bacteremia were not more resistant than those causing initial episodes. In
conclusion, most episodes of recurrent gram-negative bacteremia were relapses.
Relapses and reinfections could not be distinguished only by the length of time
between episodes or by antimicrobial susceptibility patterns.
PMID- 10194087
TI - Recurrent gram-negative bacteremia: incidence and clinical patterns.
AB - Fifty-eight patients who had at least two episodes of gram-negative bacteremia
were evaluated to define the epidemiology of recurrent bacteremia caused by these
organisms. Thirty-two patients (55%) had single relapses, 16 (28%) had one
reinfection, and 10 (17%) had more than one recurrence of bacteremia. Intravenous
catheters were the most common probable source of bacteremia. Relapses occurred
earlier after the initial episode than did reinfections (58 days vs. 292 days; P
= .002). The duration of antibiotic therapy for the first episode was shorter for
patients with relapses than for those with reinfections (13.9 days vs. 17.5 days;
P = .046). Microorganisms causing recurrent bacteremic episodes were not
unusually resistant to antimicrobial agents. Reinfections may be difficult to
prevent because they are associated with the severity of the underlying illness,
which may not improve. The frequency of relapses might be reduced by increasing
the duration of antibiotic therapy and eliminating foci of infection.
PMID- 10194088
TI - Late cytomegalovirus pneumonia in adult allogeneic blood and marrow transplant
recipients.
AB - To assess the impact of antiviral prophylaxis during the first 3 months after
transplantation on the frequency, timing, and outcome of cytomegalovirus (CMV)
pneumonia during the first year, 541 adult allogeneic blood and marrow transplant
recipients were evaluated. Thirty-four patients (6.3%) developed 35 episodes of
CMV pneumonia at a mean of 188 days after transplantation, with an associated
mortality rate of 76%. Twenty-six episodes (74%) occurred late (after day 100).
Of the patients with late CMV pneumonia almost all (92%) had chronic graft vs.
host disease or had received T cell-depleted transplants. Fourteen late CMV
pneumonias (54%) were associated with serious concurrent infections, and 100% of
these episodes were fatal. In conclusion, although the frequency of CMV pneumonia
in the early posttransplantation period may be substantially reduced by
prophylaxis, CMV continues to be a major cause of morbidity and mortality in the
late period. Some subsets of patients need more prolonged surveillance and
prophylaxis and/or preemptive therapy.
PMID- 10194089
TI - Clinical and virological monitoring during treatment with intrathecal cytarabine
in patients with AIDS-associated progressive multifocal leukoencephalopathy.
AB - We describe the clinical and virological outcome of human immunodeficiency virus
infected patients with progressive multifocal leukoencephalopathy (PML) treated
with cytarabine. Twenty-seven patients received intrathecal cytarabine, 5
received concomitant intravenous cytarabine, and 20 received concomitant
antiretroviral therapy. The median baseline CD4+ cell count was 28/mm3. After 4
weeks, 4 (19%) of 21 evaluable patients had stable disease, whereas the others
progressed. The median survival from diagnosis and from onset was 66 and 128
days, respectively. Patients with Karnofsky scores of >50 and those previously
taking antiretroviral medications had a higher probability of survival 3 months
after diagnosis (P = .003 and P = .05, respectively). Overall, after 4 weeks,
median JC virus load in CSF increased by 0.7 log10 copies/mL from baseline (P =
NS). The mean JC virus load at 4 weeks was lower in patients with stable disease
than in progressors (3.47 vs. 4.47 log10 copies/mL; P = .027). JC virus became
undetectable in the only patient who had a long-term stable condition. The
concentration of JC virus in CSF showed a correlation with clinical outcome.
PMID- 10194090
TI - Treatment of hydrocephalus secondary to cryptococcal meningitis by use of
shunting.
AB - Hydrocephalus can be associated with increased morbidity and mortality in
cryptococcal meningitis if left untreated. Both ventriculoperitoneal and
ventriculoatrial shunting have been used in persons with cryptococcosis
complicated by hydrocephalus, but the indications for and complications, success,
and timing of these interventions are not well known. To this end, we reviewed
the clinical courses of 10 non-human immunodeficiency virus-infected patients
with hydrocephalus secondary to cryptococcal meningitis who underwent shunting
procedures. Nine of 10 patients who underwent shunting had noticeable improvement
in dementia and gait. Two patients required late revision of their shunts. Shunt
placement in eight patients with acute infection did not disseminate cryptococcal
infection into the peritoneum or bloodstream, nor did shunting provide a nidus
from which Cryptococcus organisms proved difficult to eradicate. Shunting
procedures are a safe and effective therapy for hydrocephalus in patients with
cryptococcal meningitis and need not be delayed until patients are mycologically
cured.
PMID- 10194091
TI - Sustained anabolic effects of long-term androgen administration in men with AIDS
wasting.
AB - Fifty-one human immunodeficiency virus-positive men with hypogonadism and wasting
were randomized to receive testosterone enanthate, 300 mg i.m. every 3 weeks, or
placebo for 6 months, followed by open-label testosterone administration for 6
months. Subjects initially randomized to placebo gained lean body mass (LBM) only
after crossover to testosterone administration (mean change +/- standard error of
the mean, -0.6 +/- 0.7 kg [months 0-6] vs. 1.9 +/- 0.7 kg [months 6-12]; P =
.03). In contrast, subjects initially randomized to testosterone continued to
gain LBM during open-label administration (2.0 +/- 0.7 kg [months 0-6] vs. 1.6 +/
0.6 kg [months 6-12]; P = .62) and had gained more LBM at 1 year than did
subjects receiving testosterone for only the final 6 months of the study (3.7 +/-
0.8 kg vs. 1.0 +/- 1.0 kg; P = .05). Testosterone administration results in
sustained increases in LBM during 1 year of therapy in hypogonadal men with AIDS
wasting.
PMID- 10194092
TI - Effects of dengue fever during pregnancy in French Guiana.
AB - To determine the effects of dengue fever (DF) during pregnancy, pregnant women
presenting with a dengue-like syndrome at a hospital in Saint-Laurent du Maroni,
French Guiana, from 1 January 1992 to 1 April 1998 were studied. The diagnosis of
DF was made by serological tests, virus isolation on AP 61 mosquito cells, and/or
reverse transcriptase polymerase chain reaction analysis. Twenty-two women had
either probable or confirmed DF. Dengue virus serotype 2 was detected in four
cases, and dengue virus serotype 1 was detected in one. Three fetuses died
following the onset of the disease, and three cases of prematurity occurred. All
infants appeared normal during physical examination, and no neonatal DF was
diagnosed. In conclusion, DF in pregnant women did not cause any infant
abnormality, but it may have been responsible for fetal death. The rate of fetal
death associated with DF (13.6%) was much higher than the mean rate for the
gynecology unit at the hospital (1.9%). However, these differences were not
significant, and consequently these preliminary results need to be confirmed.
PMID- 10194093
TI - Seroconversion to circumsporozoite antigen of Plasmodium falciparum demonstrates
a high risk of malaria transmission in travelers to East Africa.
AB - Circumsporozoite (CS) antibodies have been shown to be reliable indicators of
malaria transmission in endemic areas. Their prevalence in travelers can indicate
the degree of exposure to plasmodial infection. Two hundred sixty-two short-term
travelers to Kenya were recruited to a prospective study to determine the
incidence of CS antibody conversion. All travelers were receiving malaria
chemoprophylaxis. Serum samples were drawn before departure and 4-6 weeks after
their return to Germany. Sera from 310 volunteers who did not leave Germany
served as controls. Serum specimens from 13 (4.96%) of the 262 travelers were
found to be positive after return. None of the travelers developed symptoms of
clinical malaria or antibodies against the blood stages of Plasmodium falciparum.
All 310 control samples tested negative. These data demonstrate a considerable
risk of malaria transmission for short-term travelers to East Africa.
PMID- 10194094
TI - Guide to major clinical trials of antiretroviral therapy in human
immunodeficiency virus-infected patients: protease inhibitors, non-nucleoside
reverse transcriptase inhibitors, and nucleotide reverse transcriptase
inhibitors.
PMID- 10194095
TI - Antibodies to human herpesvirus 8 in POEMS (polyneuropathy, organomegaly,
endocrinopathy, M protein, skin changes) syndrome with multicentric Castleman's
disease.
PMID- 10194096
TI - A traveler returning from Central Africa with fever and a skin lesion.
PMID- 10194097
TI - Successful use of liposomal amphotericin B in a case of amphotericin B-induced
nephrogenic diabetes insipidus.
PMID- 10194098
TI - Septic shock caused by Staphylococcus lugdunensis.
PMID- 10194099
TI - Mycobacterium neoaurum--an unusual cause of infection of vascular catheters: case
report and review.
PMID- 10194100
TI - Fatal infection due to extended-spectrum beta-lactamase-producing Escherichia
coli: implications for antibiotic choice for spontaneous bacterial peritonitis.
PMID- 10194101
TI - Prevotella oralis homograft-valve endocarditis complicated by aortic-root
abscess, intracardiac fistula, and complete heart block.
PMID- 10194102
TI - Severe acute respiratory failure due to legionella pneumonia treated with
extracorporeal membrane oxygenation.
PMID- 10194103
TI - Invasive sinusitis and cerebritis due to Curvularia clavata in an immunocompetent
adult.
PMID- 10194104
TI - Successful treatment of persistent vancomycin-resistant Enterococcus faecium
bacteremia with linezolid and gentamicin.
PMID- 10194105
TI - Successful treatment of adenovirus disease with intravenous cidofovir in an
unrelated stem-cell transplant recipient.
PMID- 10194106
TI - Lofgren's syndrome as the first manifestation of acute infection due to Chlamydia
pneumoniae: a prospective study.
PMID- 10194107
TI - Ochrobactrum anthropi as an agent of nosocomial septicemia in the setting of
AIDS.
PMID- 10194108
TI - Mycoplasma infections of aneurysms or vascular grafts.
PMID- 10194109
TI - Peritonitis due to Rothia dentocariosa in a patient receiving continuous
ambulatory peritoneal dialysis.
PMID- 10194110
TI - Progress report on new antiepileptic drugs: a summary of the fourth Eilat
conference (EILAT IV).
AB - The Fourth Eilat Conference on New Antiepileptic Drugs (AEDs) was held at the
Royal Beach Hotel, Eilat, Israel, from 6th to 10th September 1998.
Epileptologists and scientists from 20 countries attended the conference, which
was held to discuss a number of issues in drug development, including outcome
assessment in epilepsy (long-term efficacy, quality of life, safety), cost
effectiveness, an update on drugs in development, a progress report on recently
marketed AEDs, and controversies in strategies for drug development. This review
focuses on drugs in development and recently marketed AEDs. Drugs in development
include ADCI, AWD 131-138, DP16, ganaxolone (CCD 1042), levetiracetam (ucb L059),
losigamone, pregabalin (isobutyl GABA [CI-1008]), remacemide hydrochloride,
retigabine (D-23129), rufinamide (CGP 33101), soretolide (D2916), TV1901, and
534U87. New information on the safety and efficacy of recently marketed drugs
(felbamate, fosphenytoin, gabapentin, lamotrigine, oxcarbazepine, tiagabine,
topiramate, vigabatrin, zonisamide) and of a new antiepileptic device, the
neurocybernetic prosthesis (NCP), has become available. This paper summarizes the
presentations made at the conference.
PMID- 10194111
TI - Felbamate in refractory partial epilepsy.
AB - This open-label study was performed to evaluate efficacy and safety of Felbamate
(FBM) add-on therapy in drug-refractory partial epilepsy. We evaluated 36
patients (12 males) aged 11-68 years (mean 29.8) in which FBM was titrated
gradually from 300 mg/day to a mean total maintenance daily dose of 1936 mg.
Patients were monitored according to clinical practice and performed regularly
laboratory tests. Mean follow-up of FBM therapy was 10 months (range 2-27). In
this study, 5% of patients resulted to be seizure-free, 11% showed a seizure
reduction more than 75%, 23% decreased their seizure frequency between 50% and
75% (P = 0.0001). The adverse events which were reported more frequently were:
nausea, vomiting, anorexia and weight loss. Even if the patients sample is small
FBM proves its efficacy in partial epilepsy, showing a relatively well tolerated
profile.
PMID- 10194112
TI - Acoustic brainstem nuclei express Fos after flurothyl-induced generalized
seizures in rats.
AB - The inferior colliculus (IC) plays a key role in modulating audiogenic seizures
(AS) in rats. We investigated whether acoustic brainstem nuclei express Fos-like
immunoreactivity (FLI) after flurothyl-induced generalized seizures in rats.
Compared to controls, experimental animals showed significantly (P<0.05) more FLI
in the dorsal and external cortex of the IC, as well as in the medial part of the
medial geniculate body (MGB), perigeniculate area, and dorsal cochlear nucleus.
No significant increase of FLI was observed in the central nucleus of the IC,
ventral and dorsal parts of the MGB, dorsal nucleus of the lateral lemniscus, or
ventral cochlear nucleus. Because this pattern of FLI closely resembles that
observed after AS in previous studies, these results suggest that Fos expression
in acoustic brainstem nuclei is not specific for AS.
PMID- 10194113
TI - The novel anticonvulsant AWD 140-190 acts as a highly use-dependent sodium
channel blocker in neuronal cell preparations.
AB - The effect of the new anticonvulsant drug AWD 140-190 (4-(p-bromophenyl)-3
morpholino-1H-pyrrole-2-carboxylic acid methyl ester) on neuronal sodium channels
was evaluated in differentiated NG 108-15 cells using the patch clamp technique.
AWD 140-190 blocked neuronal sodium channels more potently than phenytoin in a
dose-dependent manner (1-30 microM). As with phenytoin, the blocking effect was
voltage and frequency dependent. However, comparing equi-effective doses of AWD
140-190 and phenytoin, the frequency dependence was two to three times stronger.
This pronounced use dependent effect of AWD 140-190 may be the reason for the
superior tolerability and anticonvulsant activity in experimental models of
epilepsy.
PMID- 10194114
TI - The significance of bilateral EEG abnormalities before and after hemispherectomy
in children with unilateral major hemisphere lesions.
AB - The rate of seizure relief following hemispherectomy varies between 50 and more
than 80%. There has been particular debate concerning the significance of
bilateral electroencephalography (EEG) abnormalities in influencing prognosis.
This study was set out to determine the frequency of bilateral EEG abnormalities
and their relationship to underlying pathology and outcome. We investigated 28
children with unilateral hemisphere lesions, who underwent hemispherectomy.
Interictal and ictal EEGs before and after hemispherectomy were reviewed. Post
operative outcome with respect to seizures was noted. Bilateral EEG abnormalities
were seen in 75%, but were more common in children with malformations of cortical
development than in patients with acquired cerebral lesions, and were found more
often in interictal than in ictal records. Post-operative EEG abnormalities were
variable and did not consistently predict outcome. Short-term outcome was
similar, irrespective of aetiology. With longer term follow-up, only 47% of
children with developmental abnormalities were still seizure-free in contrast to
77% of children with acquired abnormalities. Although the incidence of bilateral
EEG abnormalities in patients with major unilateral hemisphere lesions is high,
these findings alone should not preclude further consideration for
hemispherectomy. Our findings emphasise that the aetiology of the lesion plays a
major role in determining outcome.
PMID- 10194115
TI - Analysis of CSF amino acids in young patients with generalised refractory
epilepsy during an add-on study with lamotrigine.
AB - The effect of add-on administration of lamotrigine (1-12 mg/kg per day, 2-12
months) on the levels of neurotransmission related amino acids including gamma
aminobutyric acid (GABA), glutamate, aspartate, glycine and antiepileptic drugs
(AEDs) in lumbar cerebrospinal fluid (CSF) was studied in 22 children and young
adults with generalised therapy resistant epilepsy. Two lumbar punctures were
performed, one prior to, and one following a mean of 5 months (2-12 months) of
lamotrigine treatment. Lamotrigine decreased seizure incidence and severity in 12
of the 22 patients without influencing CSF GABA, glutamate, aspartate or glycine
levels. Lamotrigine did not alter the concentrations of AEDs in CSF or plasma.
However, CSF GABA levels were 86% higher in those patients also treated with
gamma-vinyl-GABA (vigabatrin, GVG) compared with patients treated with other
combinations and this was not altered by co-medication with lamotrigine. The
proposed mechanism of action of lamotrigine, namely that it may inhibit glutamate
release in the CNS, is not reflected by changes in CSF glutamate levels. The
present findings indicate that CSF GABA, glutamate, aspartate and glycine levels
may not be useful as in vivo neurochemical markers in young patients responding
to the therapeutic dose of lamotrigine used in this study.
PMID- 10194116
TI - Human cytomegalovirus infection of human hematopoietic progenitor cells.
AB - For a number of years it has been well established that human cytomegalovirus
(HCMV) can be transmitted by the cellular components of blood. HCMV is also
associated with a number of hematologic disorders. Although HCMV was thought to
be present in blood cells in a latent or persistent form, it was not known how
the virus was maintained and which cells were the carriers of HCMV. In addition
to peripheral blood cells, there has been clinical evidence that HCMV may be
associated with specific disorders of the hematopoietic system. Recently, a
number of advances in cell and molecular biology have helped to develop a better
understanding of the relationship between HCMV and the hematopoietic system. The
application of the polymerase chain reaction (PCR) to the study of HCMV infection
has revealed that the virus was present in mononuclear cells with only limited
transcription of its genome. Studies conducted in our laboratory have
demonstrated that both CD34+ progenitor cells and monocytes could be infected
with HCMV and virus recovered when the cells were allowed to terminally
differentiate. Subsequently, these results have been confirmed in vivo: HCMV DNA
and limited RNA transcripts could be detected in in vivo infected hematopoietic
progenitor cells and HCMV has been rescued from macrophages derived through in
vitro differentiation of monocytes from normal seropositive blood donors.
Although our understanding of the relationship between HCMV and the hematopoietic
system has been advanced, the mechanisms by which the virus can be maintained in
a latent state and how it is reactivated is still unclear. Furthermore, it
remains to be determined what HCMV-mediated effect is responsible for the
inhibition of hematopoiesis following an in vitro infection and its significance
in vivo.
PMID- 10194117
TI - Extracellular matrix receptors and the differentiation of human megakaryocytes in
vitro.
AB - We investigated the expression and functions of extracellular matrix receptors
(or integrins) in the course of the differentiation of human megakaryocytes (Mks)
leading to the formation of platelets. Integrins beta1 or Very Late Antigens
(VLA) are specialized transmembrane receptors allowing the attachment of the
cells to collagen (VLA-2), fibronectin (VLA-4 and -5) and laminin (VLA-6). A
proportion of committed megakaryocytic progenitor cells (CFU-MK) adhere to
fibronectin but not to collagen or laminin. The early immature Mks are retained
on fibronectin (30%) and laminin (12%) but not on collagen whereas large mature
Mks are still adherent to fibronectin and laminin and also acquired the capacity
to adhere to collagen. The expression of the different VLA in the maturation of
Mks correlates well with their adhesive properties. Hence, VLA-2 is not expressed
on immature Mks but is present on the mature polyploid cells. VLA-4 is detected
only on immature Mks which do not seem to bear VLA-5, while this last integrin
appears on late Mks. VLA-6 showed a broad distribution from the early to late
stages of Mks differentiation. Integrins beta3 of the cytoadhesin family are
represented by alphaIIb beta3 that is the receptor for fibrinogen and alphaV
beta3 which mediates adhesion to vitronectin. AlphaIIb beta3 is present on the
CFU-MK and highly expressed throughout the Mks maturation stages while alphaV
beta3 expression is much lower and seems to be detected only on the late Mks. The
regulation of the expression of these receptors by cytokines and their respective
roles in the maturation of Mks and the final production of platelets, are
discussed. The development of efficient culture systems of human Mks in the
presence of the recently cloned thrombopoietin will undoubtedly help to shed more
light on the molecular mechanisms of their interactions via integrins with the BM
microenvironment.
PMID- 10194118
TI - The relevance of plasminogen activator inhibitor 1 (PAI-1) as a marker for the
diagnosis of hepatic veno-occlusive disease in patients after bone marrow
transplantation.
AB - Hepatic veno-occlusive disease (VOD) is the third most important fatal
complication in allogeneic bone marrow transplantation (BMT), the second most
significant one in the autologous setting and the most severe of all the regimen
related toxicities. A growing number of VOD cases has to be expected due to the
increasing number of high dose chemotherapies given with consecutive stem cell
transplantation in patients with solid tumors. Confirmation of the diagnosis of
VOD by biopsy is associated with a high risk of severe bleeding complications
and, unfortunately, until now reliable laboratory markers have not as yet been
established. Recently, plasminogen activator inhibitor 1 (PAI-1), the main
inhibitor of the fibrinolytic system, has been found to be significantly elevated
in VOD patients probably reflecting hypofibrinolysis in these patients.
Furthermore, PAI-1 was able to distinguish between patients with VOD and those
with hyperbilirubinemia after BMT caused by graft-versus-host-disease (GVHD) or
toxic effects, in which cases the PAI-1 levels were mostly within the normal
range. In this overview we summarize the data strongly indicating that PAI-1 is a
useful marker for the diagnosis of VOD and helps in the differential diagnosis of
hyperbilirubinemia after BMT.
PMID- 10194119
TI - The concept of typical and atypical chronic lymphocytic leukaemia.
AB - Subdivision of CLL into typical and atypical subtypes, as proposed by the FAB
group in 1989, is not yet widely accepted and its clinical significance is still
debated. In recent years, however, a strong correlation was found between
atypical morphology trisomy 12 and an aberrant immunophenotype. In the first part
of this review we discuss current concepts and generally accepted data on
morphology, immunophenotype, genetic abnormalities, clinical features and
prognostic factors in CLL. Subsequently, based on our own series and other
recently published data, we analyse the validity and clinical impact of
classifying CLL into typical and atypical entities and demonstrate that they may
represent two closely related but different entities.
PMID- 10194120
TI - Detection of residual disease in acute lymphoblastic leukemia of childhood.
AB - Several techniques developed in recent years provide us with the capability to
detect sub-microscopic leukemia during remission. Quantitative polymerase chain
reaction (PCR) is thus far the most sensitive assay that is applicable in most
patients with acute lymphoblastic leukemia (ALL) of childhood. However, false
positive and false-negative results may provide the clinician with misleading
data and therefore PCR analysis should be accompanied by another assay and
changes in the level of residual disease should be confirmed at different time
points following treatment. Furthermore, several studies did not determine a
threshold of residual disease level above which relapse is likely to occur, and
more recent data show that long-term remission may be sustained in the presence
of residual disease. Thus, additional studies of the biology of residual disease
in childhood ALL should be performed before sensitive assays of residual disease
detection and quantitation can be clinically utilized.
PMID- 10194121
TI - Diagnostic approaches to acute promyelocytic leukaemia.
AB - Delivering the most effective clinical therapy in acute promyelocytic leukaemia
(APL) is dependent on accurately making the diagnosis. The morphological
diagnosis can be improved by detecting the presence of a specific chromosome
translocation, the t(15;17)(q22;q21). This can be achieved using cytogenetics, RT
PCR, FISH and anti-PML monoclonal antibody. The optimal approach will be rapid,
accurate and readily integrated into the routine haematology laboratory.
Immunofluorescent detection of microparticulate PML protein fulfils these
criteria, however, karyotyping will also detect the variant translocations and
remains the 'gold-standard'.
PMID- 10194122
TI - Ovarian injury and modern options to preserve fertility in female cancer patients
treated with high dose radio-chemotherapy for hemato-oncological neoplasias and
other cancers.
AB - High dose chemotherapy and radiotherapy have radically increased long term
survival of young cancer patients. Among the side effects of chemotherapy
treatments are ovarian failure and infertility, which are of particularly great
concern to young cancer patients. Recently, cryopreservation procedures such as
in vitro fertilization and embryo storage, or ovarian tissue cryopreservation
have been used to preserve fertility in patients subjected to cancer treatments.
Knowledge of the risks and probabilities of ovarian failure as well as the risks
of the cryopreservation procedures is crucial for patients and physicians in
order to make informed choices that will best serve the patients interests. This
article presents data of a prospective study that determines the risk of ovarian
failure following exposure to chemotherapy as well as a review of related
publications. Progressive, dose-related depletion of primordial follicles is
noted on histology, explaining the risk of undergoing premature ovarian failure
years after exposure to chemotherapy. The safety of ovarian tissue
cryopreservation procedures with a new round biopter was evaluated, as well as
the risk of malignant cell transmission. It has been shown that laproscopic
ovarian biopsy performed with the round biopter is a safe and efficient method
for collection of ovarian tissue in cancer patients. In Hodgkin's disease
patients' ovarian cortical tissue obtained for cryopreservation does not contain
malignant cells. However the risk of cryopreserving and transferring malignant
cells should be tested separately for each disease according to the risk of
ovarian metastasis and the ability to detect single malignant cells.
PMID- 10194123
TI - Significance of BCR-ABL transcripts in bone marrow aspirates of Philadelphia
negative essential thrombocythemia patients.
AB - Philadelphia-negative (Ph-neg) essential thrombocythemia (ET), polycythemia vera
(PV) and idiopathic myelofibrosis (IMF) form a syndrome of related chronic
myeloproliferative disorders (MPD) characterized by expansion of one or more of
the hematopoietic progenitors. Based on our previous finding of BCR-ABL
transcripts in bone marrow aspirates of 12/25 Ph-neg ET patients, we have
expanded our study up to 40 patients. Here we describe the rational for
performing this study and report 19 of 40 patients who have BCR-ABL transcripts
in their BM, 11 of them carry b3a2 and 8 carry b2a2. The two groups, BCR-ABL
positive and negative, were completely identical with regard to clinical
characteristics and laboratory data. We also report preliminary results of our
attempt to examine concordance or discordance of BCR-ABL expression in the
peripheral blood and bone marrow of Ph-neg ET patients.
PMID- 10194124
TI - Effects of FLT3 ligand on proliferation and survival of myeloid leukemia cells.
AB - FLT3 ligand (FL) acting through its tyrosine kinase receptor FLT3 has pleiotropic
and potent effects on hematopoietic cells. The well-described involvement of this
ligand-receptor pair in physiological hematopoiesis raised the question whether
FL and FLT3 also play a role in the pathobiology of leukemia. Following the early
discovery of high receptor expression by myeloid leukemia cells, several
investigators have focused their attention on these cells, both primary acute
myeloid leukemia (AML) cells and continuous human myeloid leukemia cell lines.
Regardless of the morphological FAB subtype, the vast majority of AML cases were
FLT3-positive both at the mRNA and protein level; among the myeloid cell lines,
predominantly the monocytic and myelocytic cell lines were FLT3-positive whereas
the erythrocytic and megakaryocytic cell lines were FLT3-negative. Virtually all
cell lines studied expressed FL transcripts; the finding that some cell lines
displayed both ligand and receptor indicates the possibility of autocrine,
intracrine or paracrine stimulatory loops. In vitro growth assays showed that FL
caused a proliferative response in a high percentage of AML cases. Only
constitutively growth factor-dependent myelocytic cell lines increased their
proliferation upon incubation with FL whereas all growth factor-independent cell
lines were refractory to FL stimulation. Combinations of FL with various
cytokines (e.g. G-CSF, GM-CSF, IL-3, M-CSF, PIXY-321, SCF) had synergistic or
additive mitogenic effects. Finally, FL had significant anti-apoptotic, survival
promoting effects on primary AML cells and myeloid cell lines under serum-free
culture conditions. On the strength of the above findings, it can be concluded
that the FL-FLT3 signaling system may play a certain, albeit probably not causal
role in the development of human leukemias. Dissection of the exact molecular
pathways that lead to proliferation and/or anti-apoptosis of myeloid leukemia
cells as well as the detailed elucidation of the possible contribution of the FL
FLT3 genes to leukemogenesis remain future challenges.
PMID- 10194125
TI - Lymphomas in patients with Sjogren's syndrome: review of the literature and
physiopathologic hypothesis.
AB - The occurrence of non Hodgkin's lymphoma (NHL) is the most serious complication
of Sjogren's syndrome (SS). Taking the opportunity to study 16 patients with
lymphoma and an underlying SS, we performed a review of literature concerning SS
and lymphoma and made an hypothesis on the physiopathology of lymphoproliferation
in patients with SS. Lymphomas occurring in patients with SS are in most cases
low grade marginal zone lymphomas (MZL). They arise frequently in mucosal
extranodal sites, not only in the salivary glands but also the stomach and the
lung. These lymphomas are not associated with viruses including hepatitis C virus
(HCV), Epstein-Barr virus, human herpes virus 8 or human T lymphotropic virus-I,
known to be present in other types of lymphomas. Some of the translocations or
mutations of oncogenes or anti-oncogenes described in other lymphomas are also
detected in SS-associated lymphomas. Lymphomas complicating SS share a number of
characteristics with lymphomas complicating HCV infection. We make the assumption
that, in both diseases, the first event of lymphomagenesis is the chronic
stimulation, on the site of the disease, of polyclonal B-cells secreting
rheumatoid factor (RF). Then, these RF B-cells may become monoclonal and
disseminate in other organs. The monoclonal secreted RF complexed with polyclonal
IgG may cryoprecipitate. The following step would be a chromosomal abnormality
(e.g. trisomy 3) which would confer to these cells a low grade B-cell lymphoma
compartment. A last event (e.g. mutation of p53) could transform this low grade B
cell lymphoma into a high grade large B-cell lymphoma. If this hypothesis was
correct, most of B-cell lymphomas associated with SS should have a surface
immunoglobulin with RF activity and should grow through an auto-antigen driven
process.
PMID- 10194126
TI - Poor treatment outcome of Philadelphia chromosome-positive pediatric acute
lymphoblastic leukemia despite intensive chemotherapy.
AB - Children with Philadelphia (Ph) chromosome positive (+) acute lymphoblastic
leukemia (ALL) represent a subgroup at very high risk for treatment failure. This
study included 1322 children enrolled between 1988 and 1994 on CCG risk-adjusted
studies for ALL who had centrally reviewed cytogenetic data. Thirty patients had
a t(9;22) and are referred to as Ph+; 1292 were Ph-. 23 of these 30 patients were
treated on the CCG-1882 high risk ALL protocol. The event-free survival (EFS)
outcome in CCG-1882 was significantly worse for Ph+ compared with Ph- patients,
with 4-year estimates of 11.3% (SD = 9.8%) and 73.4% (SD = 2.3%), respectively (p
< 0.0001).
PMID- 10194127
TI - Suppression of growth and dissemination in human pre-B leukemia cells by tumor
necrosis factor-alpha in scid mice.
AB - Tumor necrosis factor (TNF) has been shown to inhibit the growth of ALL cells.
Since the systemic administration of TNF for malignancy results in poor response
and severe toxicity, future efforts should concentrate on local treatment. Here
we examined the suppressive effect of TNF alpha on leukemic cells engrafted in
scid mice. NALM6 cells derived from pre-B ALL were injected in scid mice
subcutaneously with or without Matrigel. In mice with Matrigel, subcutaneous
tumors rapidly increased with time, whereas none of the mice without Matrigel
showed any obvious signs of disease or apparent tumors. High levels of leukemic
infiltration were observed in peripheral organs in mice with Matrigel by flow
cytometry and PCR for human beta-actin mRNA expression, while mice without
Matrigel showed low or undetectable infiltration in these organs. Human TNF alpha
was also coinjected subcutaneously with NALM6 cells and Matrigel into scid mice.
Mice with 10 ng of TNF alpha showed small subcutaneous tumors at 8 weeks, which
slowly increased. They were found to have a small number of leukemic cells in
peripheral organs by flow cytometry. By PCR, all organs with the exception of
lung and brain showed low or undetectable expression of beta-actin. However, a
large dose of TNF alpha (100 ng) had no suppressive effect on tumor growth and
leukemic infiltration in mouse organs. Similar results were obtained in colony
formation of leukemic cells in vitro. To examine the mechanism of the suppressive
effect of TNF alpha, the expression of TNF receptors in tumor cells was analyzed
by flow cytometry. Parental NALM6 expressed both TNF alpha receptors I (TNFR60)
and II (TNFR80), but these expressions were suppressed in tumor cells from mice
with Matrigel. Only TNFR80 expression was induced in tumor cells of mice with 10
ng of TNF alpha. The induction of Fas expression was also detected, whereas
neither DNA fragmentation nor apoptotic change in histology was observed in tumor
cells of mice with TNF alpha. These results suggest that the suppressive effect
of TNF alpha on the growth of leukemic cells in scid mice is mediated through the
activation of TNFR80 without apoptotic signal.
PMID- 10194128
TI - CRKL binding to BCR-ABL and BCR-ABL transformation.
AB - The SH2-SH3 domain-containing adaptor protein CRKL is the predominant tyrosine
phosphorylated protein in chronic myelogenous leukemia (CML) neutrophils and BCR
ABL-expressing cell lines. The amino terminal CRKL SH3 domain binds directly to a
proline-rich region in the C-terminus of BCR-ABL. BCR-ABL mutants with deletions
of this region were constructed to assess biologic effects of eliminating the
CRKL binding site. Yeast two-hybrid analysis and gel overlay assays show
eradication of the direct interaction of CRKL with BCR-ABL in the proline
deletion mutants. However, these BCR-ABL mutants transform myeloid cells to
growth factor independence, and in these cells CRKL is tyrosine phosphorylated
and associates with BCR-ABL. These findings suggest both direct and indirect
interactions of CRKL with BCR-ABL. Thus, disruption of the direct interaction
with BCR-ABL has not excluded a role for CRKL in BCR-ABL-mediated transformation.
PMID- 10194129
TI - Altered T cell repertoire usage in CD4 and CD8 subsets of multiple myeloma
patients, a Study of the Eastern Cooperative Oncology Group (E9487).
AB - Previous investigations have demonstrated that an expanding circulating T cell
population is able to modulate the malignant clone in multiple myeloma. More
recently, an expansion of T cell subsets exhibiting a restricted T cell
repertoire has been detected in some MM patients. To further elucidate if a
selected T cell expansion occurs in MM, we studied the T cell receptor (TCR)
variable (V) region expression from a cohort of previously diagnosed and treated
MM patients (N=37). The latter was done by assessing the reactivity of a panel of
monoclonal antibodies specific for different V region families (alpha or beta) in
combination with anti-CD4 or anti-CD8, for purified blood T cells from MM
patients. TCR V region usage in MM patients was compared to blood T cells from
age matched (N=13) control individuals. The multivariate analysis of variance did
not uncover a difference for distribution of TCR V region usage between the
normal controls and the MM cohort. However, there were individual MM patients who
had expanded T cells with specific TCR V region expression when compared to the
control group. Several MM patients had multiple, expanded CD4 and/or CD8 subsets
based on TCR V region expression. The majority of MM patients had expanded T cell
subsets that constituted less than 10% of the total blood T cell pool. However, a
few MM patients (N=3) had larger percentages (range 34-84%) of these expanded T
cell subsets within their blood T (CD3+) cells. The stage of disease and
treatment status (currently on or off therapy) did not associate with the pattern
of restricted T cell repertoire. Finally, a smaller cohort of newly diagnosed,
untreated MM patients (N=13) also demonstrated an expanded T cell repertoire.
However, these patients had more CD4 than CD8 cell subsets involved in the
altered V region expression in several Vbeta families. Thus, these results add to
the evidence that this malignant B cell disorder whether newly diagnosed or of
longer duration, may be accompanied by an altered T cell repertoire characterized
in part by expanded T cell clones.
PMID- 10194130
TI - Leukoencephalopathy in childhood acute lymphoblastic leukemia with t(1;19).
AB - To clarify the incidence of leukoencephalopathy in patients with t(1;19) and
their clinical characteristics, we studied 239 acute lymphoblastic leukemia (ALL)
cases. The 1;19 translocation was found in 20 (8.5%) of the 239 children with
ALL. Leukoencephalopathy occurred in 2 (10%) patients with t(1;19) during the
early first remission and in one case with t(1;19) at the time of central nervous
system (CNS) relapse. Leukoencephalopathy was not found during the early first
remission in patients lacking t(1;19), but did develop in 4 patients lacking
t(1;19) at the time of CNS relapse. There were no differences in age, sex,
leukocyte count, platelet count or serum lactate dehydrogenase level between
t(1;19) patients with and without leukoencephalopathy. Our results suggest the
incidence of leukoencephalopathy in patients with t(1;19) during the early first
remission to be 10%, but we can not predict which patients will develop
leukoencephalopathy.
PMID- 10194131
TI - Cytotoxicity of 2-chlorodeoxadenosine (cladribine, 2-cdA) in combination with
other chemotherapy drugs against two lymphoma cell lines.
AB - Cladribine is a purine analog with impressive activity in patients with low-grade
lymphoproliferative disorders. We studied the combination of cladribine with
other antineoplastic drugs against two human-derived B-cell lymphoma cell lines
in vitro. Cladribine was combined with cisplatin, daunorubicin, chlorambucil,
paclitaxel or etoposide. Under the experimental conditions studied, only the
combination of cladribine and cisplatin showed significantly increased
cytotoxicity compared to the effect of either drug alone.
PMID- 10194132
TI - Cytotoxic combination of loxoribine with fludarabine and mafosfamide on freshly
isolated B-chronic lymphocytic leukemia cells.
AB - Fludarabine has shown a definite clinical activity in B-cell chronic lymphocytic
leukemia (B-CLL). Recently it has been demonstrated that loxoribine, a guanine
ribonucleotide derivative, is able to increase the cytotoxicity of fludarabine in
B-CLL cells, in vitro. We have here extended these findings by testing the
activity of loxoribine in combination with fludarabine and mafosfamide. As we
have previously demonstrated, loxoribine enhances the activity of fludarabine at
all concentrations, while only lower doses of mafosfamide seem to be positively
affected by loxoribine. The combination of fludarabine and mafosfamide is
synergistic on CLL cells, and the cytotoxic activity is increased by the addition
of loxoribine. We have also evaluated the pro-apoptotic activity of each drug,
both alone and in combination; these results are concordant with the cytotoxicity
data, thus demonstrating that, even though loxoribine is more active in
combination with fludarabine than with mafosfamide, the efficacy of the triple
combination is higher than that obtained with any other agent alone or in double
combination.
PMID- 10194133
TI - Salvage chemotherapy using a combination of fludarabine and cyclophosphamide for
refractory or relapsing indolent and aggressive non-Hodgkin's lymphomas.
AB - The prognosis of patients with refractory or relapsing non-Hodgkin's lymphoma
(NHL) after primary therapy is poor and multi-drug salvage treatments are
associated with less than 60% response rates, usually of short duration. Here we
report the results of a phase II study using a fludarabine-cyclophosphamide (FAMP
Cy) combination as a salvage failure regimen in refractory and relapsing low
grade (6) and intermediate-grade (9) NHL patients. Fifteen patients, who had
received up to 4 regimens prior to therapy with FAMP-Cy were treated with
fludarabine (25 mg/m2) and cyclophosphamide (300 mg/m2) for 3 consecutive days
followed by G-CSF (5 microg/kg). The overall response was 74%, 4 achieving
complete responses (CR) and 7 partial responses (PR). All patients with low-grade
NHL responded (4 CR, 2 PR); 5 patients with intermediate-grade NHL achieved PR
lasting for a median of 5 months. The main toxicity encountered was moderate
myelosuppression. Three patients had febrile neutropenia, one had drug-induced
fever and a single patient developed severe neurotoxicity. Opportunistic
infections due to lymphopenia were not seen. The combination of fludarabine and
cyclophosphamide used as a salvage regimen showed an impressive response in a
small group of heavily pretreated low-grade NHL patients who had previously
received a large number of prior regimens. FAMP-Cy had limited effect in a
similar group of intermediate-grade NHL patients. Results with this "failure"
regimen are encouraging, however further studies are needed in order to confirm
these observations in a larger series of patients.
PMID- 10194134
TI - Other cancers in patients with gastric MALT lymphoma.
AB - Patients with Hodgkin's disease and nodal non-Hodgkin's lymphomas seem to have an
excess risk for other cancers. A high incidence of other cancers has also been
found in some series of patients with gastric MALT lymphomas. In a series of 136
patients with gastric MALT lymphomas the occurrence and features of other cancers
have been described. In order to evaluate their occurrence statistically
(excluding skin cancers) standard incidence ratios (SRI) have been calculated,
using the incidence rates of a Cancer Registry in Spain as a reference. A Cox's
multivariate proportional hazard model was fitted in order to evaluate the
influence of age, sex, histological grade and treatment with chemotherapy or
chemotherapy plus radiotherapy in the development of other non-skin cancers
occurring after the diagnosis of MALT lymphoma. Other cancers were detected in 16
of the 136 patients (11.7%); the other cancer was detected prior to MALT gastric
lymphoma in 6 patients (4.41%), concomitantly in 4 (2.9%) and after diagnosis of
the lymphoma in 6 (4.41%). Other cancers occurred in 14.4% of the male and in
8.3% of the female patients; in 12% of the patients with low grade and in 11% of
the patients with high grade lymphomas. Of the 6 cancers that occurred after
diagnosis of the gastric lymphoma, 3 did in the 80 patients (3.7%) that had been
treated with chemotherapy, 1 in the 3 cases (33%) treated with chemotherapy and
radiotherapy and 2 in the 53 patients (3.7%) who had not received chemotherapy or
radiotherapy. The most frequent other cancers were lymphoid neoplasms and gastric
carcinoma. There was not an excess of other cancers in the whole cohort or in the
sex or histological grade strata. There was an excess close to significance (SIR
=2.59; 95% CI:0.98-6.88) in the patients under 50 years of age. In the Cox's
analysis, age, sex, histological grade and treatment did not influence the
occurrence of other cancers after the diagnosis of lymphoma. In conclusion, in
patients with gastric MALT lymphoma other cancers also occur. An excess incidence
was not demonstrated, although it may exist in patients under 50 years. Of
special importance is the occurrence of gastric cancer that appears concomitantly
or after gastric lymphoma.
PMID- 10194135
TI - B-cell prolymphocytic leukemia: a survey of 35 patients emphasizing
heterogeneity, prognostic factors and evidence for a group with an indolent
course.
AB - We report a retrospective survey of 35 patients (18 males and 17 females) with B
Prolymphocytic leukemia (B-PLL) followed for a median of 63 months. Twelve
patients fulfilled Galton's original clinical and hematological criteria,
presented with prominent splenomegaly and hyperleukocytosis and showed rapid
progression soon after diagnosis. Twelve cases with gradually increasing spleen
size and prolymphocyte count had an indolent course. Seven of this group are
alive 68 to 164 months after diagnosis, whereas five died from causes unrelated
to PLL. Eleven patients who never developed impressive leukocytosis had a
variable prognosis. In the group of 17 patients treated with chlorambucil and
prednisone (CP) or cyclophosphamide, vincristine, prednisone (COP) 8 achieved a
partial remission (PR) with a median response of 32 months. In the group of six
cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) treated patients
one achieved a complete remission and two PR (median response was maintained for
30 months). Three patients treated with 2CdA achieved good PR. Six patients
remained untreated. Median survival was 65 months and the probability of overall
survival for 3, 5, and 10 years was 63%, 56% and 35%, respectively. Anemia < 11
g/dl and lymphocytosis > 100 x 10(9)/l were predictors of shorter survival in
this group of patients. Age over 70, gender, B-symptoms at presentation, spleen
size, thrombocytopenia, low IgG and complement levels, presence of
paraproteinemia and the pattern of bone marrow infiltrate were not significant.
Our findings show that all B-PLL may not have such a poor prognosis as described
in earlier reports. The existence of prior symptoms evolving gradually after
years to obvious PLL and cases with mild prolymphocytosis could possibly lead to
underdiagnosis of the entity. Identification and follow-up of such cases may
suggest a different natural history, variable prognostic features and different
survival curves for B-PLL patients. In the light of the above, we suggest that
the therapeutic approach for B-PLL should always relate to the severity of the
disease.
PMID- 10194137
TI - Tuberculosis meningitis in a patient with acute myelogenous leukemia.
AB - We present a case of tuberculous meningitis in a patient with acute myelogenous
leukemia. The patient was in complete remission; he had persistent lymphopenia
and CD4+ T lymphocytopenia. Diagnosis was complicated by the chronic and subacute
nature of symptoms; some originally thought to be secondary to depression and
chemotherapy related toxicity. Treatment was further complicated by the unusual
phenomenon of paradoxical progression of disease while on appropriate therapy.
This case illustrates the importance of consideration of mycobacteriosis in the
differential diagnosis of chronic unexplained fever complicating treatment for
acute leukemia. The natural history and essential aspects of diagnosis and
treatment of CNS tuberculosis are reviewed. The clinical significance of
unexplained CD4+ T lymphocytopenia and chronic lymphopenia in patients with
leukemia is also discussed.
PMID- 10194136
TI - The mechanisms of death of an erythroleukemic cell line by p53: involvement of
the microtubule and mitochondria.
AB - A murine erythroleukemic cell line (1-2-3) which expresses only the temperature
sensitive mutant p53 gene (Ala-to-Val substitution at codon 135) was established.
These cells showed typical characteristics of apoptosis, when they were cultured
at 32 degrees C. In this process, p53 recovered the wild-type p53 function and
the expression of the p21 (waf1/cip1/sdi1), cyclin G1 and gadd45 genes was
increased. However, no significant changes were detected in the expression of the
mdm2, bcl-2, bax, fas and fasl genes, suggesting the existence of other genes
associated with apoptosis. Genes up-regulated by p53 were screened by the mRNA
differential display method. One of the up-regulated genes was identified as the
elongation factor 1 alpha (EF-1 alpha) gene. EF-1 alpha is also a microtubule
severing protein. Upon the temperature-shift, the cells developed the morphology
and the localization of alpha-tubulin similar to those of the cells treated with
vincristine, a drug that affects microtubules. The microtubule-severing
associated with up-regulation of EF-1 alpha by p53 may be a cause of the cell
death. On the other hand, the function of cyclin G1 is not so clear despite the
fact that 1-2-3 cells showed a significant increase of the cyclin G1 gene during
the early stage of apoptosis. The yeast two-hybrid system was used to identify
cyclin G1-associated proteins. One is a cytochrome c (Cyt c) oxidase subunit II
(COXII). Cyclin G1 and COXII were co-immunoprecipitated from an extract of human
osteosarcoma cell line that expressed high levels of cyclin G1. COX activity was
also increased by temperature-shift in this cell line. The pattern of changes in
COX activity was closely reflected by the expression of the cyclin G1 gene.
Cyclin G1 and COXII associate physically with each other in vivo and that
activation of COXII by binding to cyclin G1 upregulated by p53 may be associated
with apoptosis. These two new pathways, p53-EF-1 alpha-microtubule-severing (
distortion of cytoskeleton) and p53-cyclin G1-COXII (-CytC, ATP-caspase-3
activation), may cooperate to induce apoptosis in this cell line.
PMID- 10194138
TI - Long-term third chronic phase of chronic myelogenous leukemia maintained by
interferon-alpha and methotrexate.
AB - The prognosis of blast crisis (BC) of chronic myelogenous leukemia (CML) is
extremely poor despite many efforts to induce remission with chemotherapy. We
have recently treated a long-surviving CML patient who developed three separate
episodes of BC. The administration of interferon-alpha (IFN-alpha) alone as
maintenance therapy was incapable of preventing BC, which occurred twice in the
first 2 years after the diagnosis of CML. Intensive chemotherapy using
enocitabine, mitoxantrone, and etoposide was effective to induce hematological
remission. Thereafter once per week oral administration of methotrexate (10-15
mg/week) was combined with IFN-alpha after the second BC. This treatment
succeeded in obtaining a major cytogenetic response and keeping him in third
chronic phase for 5 years until the last most recent third BC. We present here
the rare clinical course of the patient, review the past literature, and discuss
the efficacy of the combination of IFN-alpha and methotrexate in this disease.
PMID- 10194139
TI - Primary esophageal T cell lymphoma.
AB - A 60 year-old woman with primary esophageal T-cell lymphoma in clinical stage
I(E)B is presented. Immunohistologic examination showed tumor cells to be
positive for anti-LCA, anti-UCHL-1, anti-MT-1, anti-CD3 antibodies, and negative
for anti-L26 antibody. Disappearance of dysphagia and improvement in esophageal
findings were noted after 65 Gy of irradiation, and biopsy specimens from the
esophagus revealed no malignancy. Primary esophageal lymphoma is extremely rare,
and this T-cell lymphoma is only the fourth case reported in the literature.
PMID- 10194140
TI - Transition of polycythemia vera to chronic neutrophilic leukemia.
AB - Two cases of polycythemia vera (PV) had transition to a hematological condition
compatible with chronic neutrophilic leukemia (CNL) 17 and 8 years after
diagnosis, respectively. One patient was treated with carboquone followed by
hydroxyurea (HU) and the other with HU during PV phase. On transition, both had
neutrophilia with white blood cell count above 40,000/microl, elevated neutrophil
alkaline phosphatase activity, splenomegaly, normal karyotype without bcr-abl
rearrangement. Busulfan was temporally effective in controlling the neutrophil
count. However, one patient progressed to the so-called spent phase and the other
subsequently had multiple transitions between PV and CNL. These cases may
represent a form of uncommon evolution of PV and support the contention that CNL
is a type of myeloproliferative disorder and that at least some CNL cases have
derangement at the hematopoietic stem cell level.
PMID- 10194141
TI - Aerosolized bronchodilators in the intensive care unit: much ado about nothing?
PMID- 10194142
TI - Lung volume reduction surgery: is less really more?
PMID- 10194143
TI - Inhaled fenoterol-ipratropium bromide in mechanically ventilated patients with
chronic obstructive pulmonary disease.
AB - In 18 patients with chronic obstructive pulmonary disease intubated and
mechanically ventilated, we prospectively randomized 200 micrograms fenoterol-80
micrograms ipratropium bromide (four puffs) from a metered-dose inhaler (MDI)
versus 1.25 mg fenoterol-500 micrograms ipratropium bromide in 5 ml saline from a
nebulizer (NEB). Respiratory mechanics were assessed before and 30 min after the
end of each delivery by the rapid end-inspiratory airway occlusion technique. We
did vary on single breaths the inflation flow (V) from 0.2 to 1.2 L. s-1, at
constant inflation volume. The total respiratory resistance of the respiratory
system (Rrs) was partitioned into airway (Rint,rs) and tissue (DeltaRrs)
resistances. We found that Rrs was equivalently reduced, from 16.49 +/- 1.37 to
14.85 +/- 1.88 cm H2O. L-1. s with MDI (p < 0.05) and from 18.04 +/- 1.85 to
15.15 +/- 1.33 cm H2O. L-1. s with NEB (p < 0.01). Whereas the prevailing effect
of MDI was to reduce Rint,rs, that of NEB was to decrease DeltaRrs. In addition,
the V resistance of the respiratory system over the whole range of V was
significantly affected by NEB but not by MDI.
PMID- 10194144
TI - Clinical control and histopathologic outcome of asthma when using airway
hyperresponsiveness as an additional guide to long-term treatment. The AMPUL
Study Group.
AB - According to international guidelines, the level and adjustment of
antiinflammatory treatment for asthma are based solely on symptoms and lung
function. We investigated whether a treatment strategy aimed at reducing airway
hyperresponsiveness (AHR strategy) in addition to the recommendations in the
existing guidelines (reference strategy) led to: (1) more effective control of
asthma; and (2) greater improvement of chronic airways inflammation. To
accomplish this, we conducted a randomized, prospective, parallel trial involving
75 adults with mild to moderate asthma who visited a clinic every 3 mo for 2 yr.
At each visit, FEV1 and AHR to methacholine were assessed, and subjects kept
diaries of symptoms, beta2-agonist use, and peak expiratory flow (PEF).
Medication with corticosteroids (four levels) was adjusted according to a
stepwise approach (reference strategy), to which four severity classes of AHR
were added (AHR strategy). At entry and after 2 yr, bronchial biopsies were
obtained by fiberoptic bronchoscopy. Patients treated according to the AHR
strategy had a 1.8-fold lower rate of mild exacerbations than did patients in the
reference strategy group (0. 23 and 0.43 exacerbation/yr/patient, respectively).
FEV1 also improved to a significantly greater extent in the AHR strategy group (p
= 0.05). In bronchial biopsies this was accompanied by a greater reduction in
thickness of the subepithelial reticular layer in the AHR strategy group than in
the reference strategy group (mean difference [95% confidence interval (CI): 1.7
micrometers (0.2 to 3.1) micrometers]). The changes in AHR in both strategy
groups were correlated with eosinophil counts in the biopsies (r = -0.48, p =
0.003). We conclude that reducing AHR in conjunction with optimizing symptoms and
lung function leads to more effective control of asthma while alleviating chronic
airways inflammation. This implies a role for the monitoring of AHR or other
surrogate markers of inflammation in the long-term management of asthma.
PMID- 10194145
TI - Assessment of abdominal muscle contractility, strength, and fatigue.
AB - We evaluated abdominal muscle contractility and fatigue by measuring twitch
gastric pressure (Pgat) after percutaneous supramaximal electrical stimulation of
the abdominal wall before and after sit-ups to task failure. Mouth pressures
during maximal voluntary expulsive maneuvers (PEmax) at TLC and FRC with
superimposed twitches, and maximum voluntary ventilation (MVV) were also
assessed. Mean fresh Pgat was 36.1 +/- 3.0 cm H2O with a coefficient of variation
that ranged between 3.0 to 4.8%. Pgat decreased by 25% (p < 0.001) and 37% (p <
0.001) at 1 and 30 min after sit-ups. During maximal voluntary contraction twitch
occlusion never occurred. PEmax at TLC and FRC decreased by 15% (p < 0.001) and
11% (p < 0.017) at 1 min, and 8% (p < 0.036) and 9% (p < 0.030) at 30 min after
sit-ups, respectively. Despite the abdominal muscle fatigue, MVV values at 1 and
30 min after sit-ups were not significantly different from the value obtained
before the sit-ups. We conclude that (1) Pgat is a useful objective indicator of
abdominal muscle contractility and fatigue; (2) during maximal voluntary
expulsive maneuvers the abdominal muscles are never fully activated; (3) sit-ups
lead to substantial low-frequency fatigue but little high-frequency fatigue of
the abdominal muscles, which has little effect on maximal breathing capacity.
PMID- 10194146
TI - Treatment of idiopathic pulmonary fibrosis with a new antifibrotic agent,
pirfenidone: results of a prospective, open-label Phase II study.
AB - Idiopathic pulmonary fibrosis (IPF) is a progressive clinical syndrome of unknown
etiology and fatal outcome. Currently available therapies are ineffective and
associated with significant adverse effects. Pirfenidone, a new, investigational
antifibrotic agent, was evaluated for its tolerability and usefulness in
terminally ill patients with advanced IPF. Consecutive patients with IPF and
deterioration despite conventional therapy or who were unable to tolerate or
unwilling to try conventional therapy were treated with oral pirfenidone.
Treatment was administered on a compassionate basis (open-label). Fifty-four
patients were followed for mortality, change in lung function, and adverse
effects. Their mean age was 62, mean duration of symptoms 4.6 yr, and time since
lung biopsy was 3.2 yr. Conventional therapy was discontinued in 38 of 46
patients; the other eight were able to decrease their prednisone dosage and eight
had no previous conventional treatment. One- and 2-yr survival was 78% (95% CI
66%, 89%) and 63% (95% CI 50%, 76%), respectively. Patients whose lung functions
had deteriorated prior to enrollment appeared to stabilize after beginning
treatment. Adverse effects were relatively minor. The results of this study are
encouraging. Pirfenidone is a promising new treatment for IPF that is well
tolerated.
PMID- 10194147
TI - Effect of body position changes on pulmonary gas exchange in Eisenmenger's
syndrome.
AB - Preliminary studies on sleep of patients with congenital heart disease and
Eisenmenger's syndrome (ES) at our institution demonstrated nocturnal worsening
arterial unsaturation, which appeared to be a body position-related phenomenon.
To investigate the potential effect of body position on gas exchange in ES, we
carried out a prospective study of 28 patients (mean age, 34.8 +/- 11.7 yr) with
established ES due to congenital heart disease. In every patient, arterial blood
gases were performed during both sitting and supine positions under three
different conditions: room air, while breathing 100% oxygen, and after breathing
oxygen at a flow rate of 3 L/min through nasal prongs. Alveolar oxygen pressure
(PaO2) for the calculation of alveolar-arterial oxygen tension differences
(AaPO2) was derived from the alveolar gas equation using PaCO2 and assuming R =
1. We used paired t test, repeated-measures two-way ANOVA with Bonferroni's test,
and regression analysis. From sitting to supine position on room air, there was a
significant decrease in PaO2 (from 52.5 +/- 7.5 to 47.5 +/- 5.5 mm Hg; p < 0.
001) and SaO2 (from 86.7 +/- 4.6 to 83.3 +/- 4.9%; p < 0.001), both of which were
corrected by nasal O2 (to 68.2 +/- 21 mm Hg and to 92 +/- 4%, respectively, p <
0.005). PaCO2 and pH remained unchanged. The magnitude of the change in PaO2
correlated with the change in AaPO2 on room air (r = 0.77; p < 0.01) but not with
the change in AaPO2 on 100% oxygen. It is concluded that in adult patients with
ES there is a significant decrease in PaO2 and SaO2 when they change from the
sitting to the supine position. A ventilation-perfusion (V/Q) distribution
abnormality and/or a diffusion limitation phenomenon rather than an increase in
true shunt may be the mechanisms responsible for this finding. The response to
nasal O 2 we observed warrants a trial with long-term nocturnal oxygen therapy in
these patients.
PMID- 10194148
TI - Long-term topical exposure to toluene diisocyanate in mice leads to antibody
production and in vivo airway hyperresponsiveness three hours after intranasal
challenge.
AB - Toluene diisocyanate (TDI) is a low-molecular-weight compound which is known to
cause occupational asthma in 5 to 10% of exposed workers. Previously, we
developed a murine model to investigate TDI-induced occupational asthma. Short
term exposure to TDI (skin sensitization twice daily on Day 0 and Day 1 and
intranasal challenge on Day 8) led to a nonspecific tracheal hyperractivity 24 h
after the challenge in TDI-sensitized mice when compared with nonsensitized mice
whereas no TDI-specific IgE antibodies were found in the serum. Because 20% of
subjects with TDI-induced occupational asthma exhibit an increase in serum IgE
antibodies, we exposed mice for a longer period of time to investigate whether
this procedure could induce TDI-specific antibody production in exposed mice.
Long-term exposure (skin sensitization on 6 consecutive weeks followed by
intranasal challenge on Week 7) resulted in the production of total IgE and IgG
and TDI-specific IgE and IgG antibodies. Airway reactivity to various agonists
was also measured in vitro and in vivo in long-term exposed mice. TDI-sensitized
mice exhibited in vitro tracheal hyperreactivity to carbachol 3 h after the
challenge when compared with the nonsensitized mice. Moreover, in vivo airway
hyperresponsiveness to serotonin (5-hydroxytryptamine [5HT]) was found 3 h after
the challenge in TDI-sensitized mice. Interestingly, in vivo airway
hyperresponsiveness was not observed at any time point in the mice exposed to TDI
according to the short-term protocol. In conclusion, by altering the exposure
time and/or cumulative dosage of TDI different biological reactions can be
elicited in exposed mice. This important finding might be a reflection of the
diversity of symptoms found in patients suffering from TDI-induced asthma. Both
the short-exposure and the long-exposure model will be useful to further
investigate the mechanisms of action of TDI.
PMID- 10194149
TI - Foci of tuberculosis transmission in central Los Angeles.
AB - To identify sites of tuberculosis transmission and to determine the contribution
of HIV-infected patients to tuberculosis morbidity in an urban area, we
prospectively evaluated 249 patients with culture-proven tuberculosis in central
Los Angeles. Restriction fragment length polymorphism (RFLP) analysis was
performed on Mycobacterium tuberculosis isolates to identify patients infected
with the same strain. Using RFLP and clinical and epidemiologic data, we
identified the most likely source case and site of transmission for 79 patients.
Homelessness, birth in the United States and Native American ethnicity were
independent predictors of being a source case, but HIV infection was not. Three
homeless shelters were sites of tuberculosis transmission for 55 (70%) of the 79
patients. HIV-infected patients constituted 27% (66/249) of the study population,
but only 17% (13/79) of patients were infected by an HIV-infected source case. We
conclude that transmission of tuberculosis in central Los Angeles was highly
focal, and that the major transmission sites were three homeless shelters. HIV-
infected tuberculosis patients did not play a major role in spread of
tuberculosis. Tuberculosis control measures targeted at specific homeless
shelters can reduce tuberculosis morbidity in urban areas where homelessness is
common and the incidence of tuberculosis is high.
PMID- 10194150
TI - The effect of mode, inspiratory time, and positive end-expiratory pressure on
partial liquid ventilation.
AB - Partial liquid ventilation (PLV) has been shown to be an effective means of
improving oxygenation in the injured lung. However, little is known about how
approach to ventilation during PLV affects gas exchange and pulmonary mechanics.
We hypothesized that gas exchange and pulmonary mechanics would be best with
positive end-expiratory pressure (PEEP) set above the lower inflection point
(LIP) of the pressure-volume (P-V) curve regardless of mode of ventilation or
inspiratory to expiratory time (I:E) ratio and that the efficiency of ventilation
would be greatest with volume-controlled ventilation (VCV) compared with pressure
controlled ventilation (PCV) and with long inspiratory time as compared with
short inspiratory time. Lung injury was induced in 14 sheep by lavage, 10 of
which were studied. Sheep were then assigned to high-PEEP (Group H, n = 5) and
low-PEEP (Group L, n = 5) groups. In Group H applied PEEP was set at the LIP and
in Group L applied PEEP was set at 5 cm H2O after the lung was filled with
perflubron (PFB). We randomly compared VCV and PCV with I:E ratios of 1:2, 1:1,
and 2:1. Peak inspiratory pressure and VT were adjusted to maintain a constant
end-inspiratory plateau pressure (Pplat) of about 25 cm H2O in both groups and a
constant total PEEP of about 5 cm H2O in Group L and about 12 cm H2O in Group H.
There were no differences in oxygenation among modes in Group H. In Group L VCV
2:1 and all of the PCV modes in Group L had a lower PaO2 than VCV 1:1 (p < 0.05).
PaCO2 and VD/VT were significantly different (p < 0.05) among modes. VD/VT was
highest during PCV 1:2 with PEEP of 5 cm H2O (p < 0.05). Quasi-static compliance
in Group H was higher than in Group L (p < 0.05). We conclude that during low
PEEP gas exchange deteriorated in VCV with long inspiratory time and in PCV.
Oxygenation was enhanced during VCV 1:1 when compared with VCV at longer I:E
ratios or PCV at any I:E ratio. With PEEP set at the LIP, adequate gas exchange
and improved lung mechanics could be obtained in all modes assessed.
PMID- 10194151
TI - Can intensive support improve continuous positive airway pressure use in patients
with the sleep apnea/hypopnea syndrome?
AB - Continuous positive airway pressure (CPAP) therapy is widely prescribed for
patients with the sleep apnea/hypopnea syndrome (SAHS), but the use of CPAP for
such patients is disappointingly low. We postulated that providing intensive
educational programs and nursing support to SAHS patients might improve CPAP use
and outcomes. We also examined the hypothesis that CPAP use would be greater
among patients who had initiated their own referral than among those asked to
seek help by a partner. We randomized 80 consecutive, new patients with SAHS to
receive either usual support or additional nursing input including CPAP education
at home and involving their partners, a 3-night trial of CPAP in our
institution's sleep center, and additional home visits once they had begun CPAP.
The primary outcome variable was objective CPAP use; symptoms, mood, and
cognitive function were also assessed after 6 mo. CPAP use over 6 mo was greater
(p = 0.003) among patients receiving intensive than among those receiving
standard support (5.4 +/- 0.3 versus 3.9 +/- 0. 4 h/night [mean +/- SEM]), with
greater improvements (p < 0.05) in SAHS symptoms, mood, and reaction time in the
intensively supported group. CPAP use was greater (p = 0.002) among patients who
initiated their own referrals. CPAP use and outcomes of therapy can be improved
by provision of a nurse-led intensive CPAP education and support program. CPAP
use is lower among patients whose partners ask them to seek treatment.
PMID- 10194152
TI - Hyperventilation with dry air increases airway surface fluid osmolality in canine
peripheral airways.
AB - Hyperventilation-induced bronchoconstriction (HIB) is a component of exercise
induced asthma (EIA) believed to result from the penetration of unconditioned air
into the lung periphery. We used a canine model of EIA to examine the effect of
hyperventilation on airway surface fluid (ASF) volume and osmolality, and to
determine if the observed kinetics support the hypothesis that hyperventilation
induced changes in ASF osmolality initiate bronchoconstriction. Exposure of
sublobar airways to dry air at baseline insufflation resulted in stable
measurements of ASF volume, ASF osmolality, and peripheral airway resistance
(Rp). Baseline insufflation of warm humidified air increased ASF volume, but did
not alter ASF osmolality. Hyperventilation challenge with warm humidified air
(WAC) increased Rp and ASF volume, but decreased ASF osmolality. Dry air
challenge (DAC) increased Rp, ASF volume, and ASF osmolality. ASF osmolality
during DAC was markedly higher when compared with posthyperventilation values.
Post-DAC changes in (Delta) ASF volume and osmolality were poorly correlated with
the development of HIB. In contrast to Delta ASF after DAC, Delta ASF osmolality
during DAC was strongly correlated with HIB, and tended to be inversely related
to Delta ASF volume. These observations are consistent with the hypothesis that
changes in airway osmolality during hyperventilation initiate peripheral airway
constriction.
PMID- 10194153
TI - Long-term use of CPAP therapy for sleep apnea/hypopnea syndrome.
AB - Patients with the sleep apnea/hypopnea syndrome (SAHS) treated by nasal
continuous positive airway pressure (CPAP) need to use CPAP long-term to prevent
recurrence of symptoms. It is thus important to clarify the level of long-term
CPAP use and the factors influencing long-term use. We examined determinants of
objective CPAP use in 1, 211 consecutive patients with SAHS who were prescribed a
CPAP trial between 1986 and 1997. Prospective CPAP use data were available in 1,
155 (95.4%), with a median follow-up of 22 mo (interquartile range [IQR], 12 to
36 mo). Fifty-two (4.5%) patients refused CPAP treatment (these were more often
female and current smokers); 1,103 patients took CPAP home, and during follow-up
20% stopped treatment, primarily because of a lack of benefit. Methods of
survival analysis showed that 68% of patients continued treatment at 5 yr.
Independent predictors of long-term CPAP use were snoring history, apnea/hypopnea
index (AHI), and Epworth score; 86% of patients with Epworth > 10 and an AHI >/=
30 were still using CPAP at 3 yr. Average nightly CPAP use within the first 3 mo
was strongly predictive of long-term use. We conclude that long-term CPAP use is
related to disease severity and subjective sleepiness and can be predicted within
3 mo.
PMID- 10194154
TI - Surfactant protein levels in severe respiratory syncytial virus infection.
AB - Infection with respiratory syncytial virus (RSV) is a common cause of respiratory
disease in infancy. Surfactant phospholipids have been shown to be reduced in
severe RSV infection. Reduction in surfactant proteins might also contribute to
the pathogenesis of this disease. We investigated daily levels of surfactant
proteins in bronchoalveolar lavage (BAL) fluid from 18 ventilated infants with
RSV infection (median age 3.1 mo) and in a control group of 16 ventilated
surgical patients (median age 0.4 mo). Surfactant proteins were measured by
ELISA, total protein by the Lowry method. Surfactant protein A (SP-A) was reduced
in BAL fluid from children with RSV infection (median 5.6 micrograms/ml; range
0.6 to 151.9 micrograms/ml) compared with control samples (median 9.0
micrograms/ml; range 0.5 to 139.6 micrograms/ml, p = 0.0368). Surfactant protein
B (SP-B) was lower in the RSV group (median 12.0 ng/ml; range 0 to 60. 8 ng/ml)
than in control patients (median 118.1 ng/ml; range 0 to 778.2 ng/ml, p <
0.0000). Surfactant protein D (SP-D) was also reduced in the RSV group (median
130.3 ng/ml; range 0 to 1,486.0 ng/ml) versus median 600.4 ng/ml; range 0 to
1,869.0 ng/ml, p < 0. 0000. Total protein levels were higher in the RSV group
(median 0.49 mg/ml; range 0.13 to 2.46 mg/ml versus median 0.36 mg/ml; range 0.07
to 1.65 mg/ml, p = 0.0079). The median value of SP-A was significantly lower in
the initial sample (2.3 micrograms/ml) than in the final one (6.0 micrograms/ml).
However, no significant correlation was found between surfactant protein
concentrations and disease severity measured by arterial alveolar oxygen ratio.
We conclude that alterations in surfactant protein concentrations are present in
severe RSV infection and speculate that these may contribute to the abnormalities
of lung function seen in this condition.
PMID- 10194155
TI - Pulmonary auscultatory skills during training in internal medicine and family
practice.
AB - We conducted a multicenter, cross-sectional assessment of pulmonary auscultatory
skills among medical students and housestaff. Our study included 194 medical
students, 18 pulmonary fellows, and 656 generalists-in-training from 17 internal
medicine and 23 family practice programs in the Mid- Atlantic area of the United
States. All participants listened to 10 pulmonary events recorded directly from
patients, and answered by completing a multiple choice questionnaire. Proficiency
scores were expressed as the percentage of respondents per year and type of
training who correctly identified each event. In addition, we calculated a series
of cumulative scores for sound recognition, disease identification, and basic
knowledge of lung auscultation. Trainees' cumulative scores ranged from 0 to 85
for both internal medicine and family practice residents (median = 40). On
average, internal medicine and family practice trainees recognized less than half
of all respiratory events, with little improvement per year of training, and were
not significantly better than medical students in their scores. Pulmonary fellows
had the highest diagnostic and knowledge scores of all groups. These data
indicate that there is very little difference in auscultatory proficiency between
internal medicine and family practice trainees, and suggest the need for
revisiting these time-honored skills during residency training.
PMID- 10194156
TI - Assessment of nitric oxide formation during exercise.
AB - We measured the end-tidal plateau in exhaled NO concentration (CETNO) by
chemiluminescence and calculated the product of V E and CETNO (V NO) in nine
healthy subjects at rest and during three intensities of cycling exercise (30%,
60%, and 90% V O2max), two levels of hyperventilation (V E = 42.8 +/- 9.1 L/min
and 84.2 +/- 6. 6 L/min), and during breathing of hypoxic gas mixtures (five
subjects, FIO2 = 14%) at rest and during exercise at 90% V O2max. Immediately
after each trial we also measured exhaled [NO] at constant expiratory flow rates
([NO]CF) of 46 ml/s and 950 ml/s, utilizing added expiratory resistance to
increase mouth pressure and close the velum (Silkoff and colleagues, Am. J.
Respir. Crit. Care Med. 1997;155:260). CETNO decreased and V NO increased above
resting levels with increasing exercise intensity during hyperventilation and
during hypoxic exercise (p < 0.05). [NO]CF, measured at either 46 ml/s or 950
ml/s, did not increase under any of the conditions investigated (exercise,
hyperventilation, or hypoxia). Venous blood from seven of the subjects was
sampled for the measurement of plasma [NO3-]. Resting plasma [NO3-] averaged 42.5
+/- 14.7 micromol/L, with no change during exercise, hyperventilation, or
hypoxia. On the basis of these results we conclude that reported increases in V
NO do not reflect an exercise-induced augmentation of systemic and/or airway NO
production. Rather, the increases in V NO during exercise or hyperventilation are
a function of high airflow rates, which reduce the luminal [NO]. This decreases
the concentration gradient for NO between the alveolar space and pulmonary
capillary blood, which results in a decrease in the fraction of NO taken up by
the blood and an increase in the volume of NO recovered in the exhaled air (V
NO).
PMID- 10194157
TI - Ozone exposure increases aldehydes in epithelial lining fluid in human lung.
AB - We hypothesized that exposure of healthy humans to ozone causes both ozonation
and peroxidation of lipids in lung epithelial lining fluid. Twelve smokers and 15
nonsmokers (eight lung function "responders" and seven "nonresponders") were
exposed once to air and twice to 0. 22 ppm ozone for 4 h with exercise in an
environmental chamber, with each exposure separated by at least 3 wk.
Bronchoalveolar lavage (BAL) was performed immediately after one ozone exposure
and 18 h after the other ozone exposure. BAL fluid was analyzed for the aldehyde
products of ozonation and lipid peroxidation, nonanal (C9) and hexanal (C6), as
well as total protein, albumin, and immunoglobulin M as markers of changes in
epithelial permeability. Ozone exposure resulted in a significant early increase
in C9 (p = 0. 0001), with no statistically significant relationship between
increases in C9 and lung function changes, airway inflammation, or changes in
epithelial permeability. Increases in C6 levels were not statistically
significant (p = 0.16). Both C9 and C6 levels returned to baseline by 18 h after
exposure. These studies confirm that exposure to ozone with exercise, at
concentrations relevant to urban outdoor air, results in ozonation of lipids in
the airway epithelial lining fluid of humans.
PMID- 10194158
TI - Human neutrophil elastase augments fibroblast-mediated contraction of released
collagen gels.
AB - In the present study, we tested the hypothesis that neutrophil elastase (NE)
might mediate remodeling of extracellular matrix by affecting fibroblast-mediated
contraction of three-dimensional collagen gels. Human lung fibroblasts were cast
into type I collagen gels containing NE. After gelation, the gels were released
into medium and the area was measured by image analyzer. NE augmented gel
contraction (p < 0.001). This was not due to cell proliferation or to degradation
to soluble collagen fragments because the amounts of DNA and hydroxyproline were
not altered. alpha1-Protease inhibitor and the synthetic inhibitor of NE, L
680,833, when added in sufficient amount to inhibit free elastase activity,
blocked the contraction induced by NE. Furthermore, neutrophil granulocytes (PMN)
in coculture, as well as conditioned media from PMN, resulted in an increased
contractility (p < 0.001 for both). Bronchoalveolar lavage fluid (BALF) from
patients with increased PMN in their lower respiratory tract and free elastase
activity had augmentive activity for gel contraction which could be partially
blocked by the inhibitors. We conclude that NE augments fibroblast-mediated
contraction of collagen gels. The findings support the notion that products
secreted by PMN in inflammatory disorders may lead to rearrangement of
extracellular matrix and could subsequently lead to tissue dysfunction.
PMID- 10194159
TI - Entrainment of blood pressure and heart rate oscillations by periodic breathing.
AB - Cheyne-Stokes respiration (CSR) is a form of periodic breathing associated with
periodic oscillations in blood pressure (BP) and heart rate (HR), which have been
attributed to hypoxia and arousals from sleep. We hypothesized that periodic
alterations in ventilation alone would promote oscillations in BP and HR. Seven
healthy, wakeful subjects breathed in three patterns, as follows: (1) regular
breathing (RB); (2) periodic breathing with three (PB3: cycle frequency = 0.035
Hz) augmented breaths alternating with 20-s apneas; and (3) periodic breathing
with five (PB5: cycle frequency = 0.030 Hz) augmented breaths alternating with 20
s apneas. SaO2 remained above 95% throughout. During periodic breathing, peaks in
BP and HR occurred during the ventilatory period and troughs occurred during
apnea. The magnitudes of systolic BP oscillations increased significantly from RB
(14 +/- 5 mm Hg) to PB3 (20 +/- 4 mm Hg) and PB5 (25 +/- 7 mm Hg; p < 0.005). HR
oscillations also increased from regular breathing (13 +/- 6.0 beats/min) to PB3
(20.2 +/- 2.3 beats/min) and PB5 (20.2 +/- 4.7 beats/ min; p < 0.01). Spectral
analysis showed that during periodic breathing there were discrete peaks in the
spectral power of ventilation, BP, and R-wave-to-R-wave interval at the periodic
breathing cycle frequencies. We conclude that oscillations in ventilation
occurring during periodic breathing can amplify and entrain oscillations in BP
and HR in the absence of hypoxia or arousals from sleep.
PMID- 10194160
TI - Patient perception of sleep quality and etiology of sleep disruption in the
intensive care unit.
AB - The etiology of sleep disruption in patients in intensive care units (ICUs) is
poorly understood, but is thought to be related to environmental stimuli,
especially noise. We sampled 203 patients (121 males and 82 females) from
different ICUs (cardiac [CCU], cardiac stepdown [CICU], medical [MICU], and
surgical [SICU]) by questionnaire on the day of their discharge from the unit, to
determine the perceived effect of environmental stimuli on sleep disturbances in
the ICU. Perceived ICU sleep quality was significantly poorer than baseline sleep
at home (p = 0.0001). Perceived sleep quality and daytime sleepiness did not
change over the course of the patients' stays in the ICU, nor were there any
significant differences (p > 0.05) in these parameters among respective units.
Disruption from human interventions and diagnostic testing were perceived to be
as disruptive to sleep as was environmental noise. In general, patients in the
MICU appeared to be more susceptible to sleep disruptions from environmental
factors than patients in the other ICUs. Our data show that: (1) poor sleep
quality and daytime sleepiness are problems common to all types of ICUs, and
affect a broad spectrum of patients; and (2) the environmental etiologies of
sleep disruption in the ICU are multifactorial.
PMID- 10194161
TI - Diurnal variation in lung function in subgroups from two Dutch populations:
consequences for longitudinal analysis.
AB - We studied circadian variation in FVC, FEV1, PEF, TLC, VC, and RV between 9:00
A.M. and 9:00 P.M. and analyzed how this variation affected estimated
longitudinal change. Data from 876 adults were obtained in a longitudinal survey
of samples from two Dutch areas. Subjects participated in four surveys held at 3
yr intervals between 1975 and 1985. FVC, FEV1, PEF, and VC increased from 9:00
A.M. until noon and decreased afterwards. TLC was constant over the day, whereas
RV decreased from 9:00 A.M. to noon. Average variation in FVC, FEV1 and PEF,
expressed as percentages of average level, was 4. 8% (200 ml), 2.8% (86 ml), and
3.1% (250 ml/s), respectively. These results are compatible with circadian
changes in airway size. No differences in variability were found between men and
women. Significantly larger changes between 9:00 A.M. and noon were found in
young adults, smokers, and those with respiratory symptoms than in other
subgroups. Adjustment for diurnal variation reduced, albeit slightly, residual
standard deviations of estimated longitudinal declines. Average diurnal change
was large relative to underlying longitudinal change. Its effect on longitudinal
change within an individual can therefore be large depending on age, smoking
habits, symptomatology, number of visits, time of measurement, and difference in
time between measurements. However, when people are measured at random times
during the day for at least three visits, or when measurements are made after
11:00 A.M., effects of diurnal variation in pulmonary function on estimated
average longitudinal decline are minimal.
PMID- 10194162
TI - Pressure-volume curves and compliance in acute lung injury: evidence of
recruitment above the lower inflection point.
AB - Measuring elastic pressure-volume (Pel-V) curves of the respiratory system and
the volume recruited by a positive end-expiratory pressure (PEEP) allows one to
study the pressure range over which recruitment occurs in acute lung injury
(ALI), and to explain how recruitment affects the compliance. Pel-V curves were
measured with the low flow inflation technique in 11 patients mechanically
ventilated for ALI. Curve I was recorded during inflation from the volume
attained after a prolonged expiration (6 s) at PEEP (9.0 +/- 2.2 cm H2O), and
Curve II after expiration to the elastic equilibrium volume at zero end
expiratory pressure (ZEEP). By using the end-expiratory volume of the breaths,
the curves were aligned on a common volume axis to determine the effect of a
single complete expiration. In each patient, Curve II (from ZEEP) was shifted
toward lower volumes than Curve I. The volume shift, probably due to
derecruitment, was 205 +/- 100 ml at 15 cm H2O (p < 0.01) and 78 +/- 93 ml at 30
cm H2O (p < 0.01); thus, during inflation from ZEEP, the volume deficit was
successively regained over a pressure range up to at least 30 cm H2O. At any
pressure, compliance was higher on the curve from ZEEP than from PEEP, by 10.0 +/
8.7 ml/cm H2O at 15 cm H2O (p < 0.01), and by 5.4 +/- 5.5 at 30 cm H2O (p <
0.01). It is concluded that in ALI, a single expiration to ZEEP leads to lung
collapse. High compliance during insufflation from ZEEP indicates that lung
recruitment happens far above the lower inflection point of the Pel-V curve.
PMID- 10194163
TI - Bone mineral density in perimenopausal women with asthma: a population-based
cross-sectional study.
AB - It is not known whether asthma constitutes a risk factor for osteoporosis or what
the impact is of inhaled corticosteroids on bone mineral density (BMD). The study
population (n = 3,222) was a random stratified sample from the Kuopio
Osteoporosis Study, which included all women 47 to 56 yr of age residing in
Kuopio Province, Eastern Finland. Spinal and femoral BMDs were measured using
dual-energy X-ray absorptiometry. The BMD values of 119 asthmatics were cross
sectionally compared with those of 3,103 nonasthmatics. Of the 119 asthmatic
women, 28 had not used corticosteroids, 65 had used oral corticosteroids, and 26
had used only inhaled corticosteroids. The asthmatics with no hormone replacement
therapy (HRT) (n = 83) had lower mean spinal and femoral BMD value than did the
corresponding nonasthmatics (spinal BMD, 1.083 +/- 0.150 [SD] versus 1.128 +/-
0.160 g/cm2, p < 0.05; femoral BMD, 0.894 +/- 0.112 [SD] versus 0.929 +/- 0.128
g/cm2, p < 0.05). Although BMDs were not significantly decreased in the
asthmatics who had used inhaled corticosteroids, the duration of use correlated
negatively with spinal BMD and was also associated with spinal BMD in multiple
regression analysis. In perimenopausal women, asthma is associated with decreased
bone density. This may be due to the corticosteroids rather than to the disease
itself. However, HRT appears to be protective against bone loss also in
asthmatics.
PMID- 10194164
TI - Effects of norepinephrine on the renal vasculature in normal and endotoxemic
dogs.
AB - Septic shock is often complicated by systemic hypotension despite normal or
increased cardiac output. Restoration of arterial pressure usually requires the
administration of systemic vasopressor agents, such as norepinephrine. However,
because norepinephrine induces vasoconstriction in other vascular beds, it may
decrease visceral blood flow, impairing visceral organ function. Because sepsis
is often associated with impaired peripheral vascular responsiveness, we
hypothesized that, unlike in normal circulatory conditions, norepinephrine would
improve visceral organ blood flow in sepsis by selectively increasing organ
perfusion pressure. Thus, in nine pentobarbital-anesthetized, mechanically
ventilated dogs, we measured the effect of norepinephrine infusion (0.3
microgram/kg/min) on renal, hepatic, and portal steady-state pressure-flow
relations (P/Q) and the dynamic vascular P/Q, created by transient inferior vena
caval occlusion, under basal and endotoxic conditions. Norepinephrine increased
organ perfusion pressures during both control and endotoxemic conditions.
However, even after controlling for the pressure effect using a general linear
model, NE was associated with an increase in renal blood flow both before and
after endotoxin administration. We conclude that, unlike the effects of
administering norepinephrine under baseline conditions, norepinephrine infusion
during endotoxic shock actually increases renal blood flow and that this effect
is not the result of an increase in perfusion pressure alone.
PMID- 10194165
TI - Effect of nitric oxide on rhinovirus replication and virus-induced interleukin-8
elaboration.
AB - Nitric oxide (NO) has been reported to have disparate effects in different viral
infections. We conducted a study to determine whether rhinovirus (RV) infection
is associated with production of NO, and to assess the effect of NO on RV-induced
interleukin-8 (IL-8) elaboration both in vitro in monolayers of BEAS-2B cells, an
immortalized respiratory epithelial cell line, and in MRC-5 cells, a diploid
human embryonic lung fibroblast cell line, challenged with purified RV type 39,
as well as in vivo, in experimental infections with RV type 23. Virus replication
was not affected by pretreatment of cell monolayers with any of three different
NO donors, and RV infection did not stimulate production of NO. Pretreatment of
cell monolayers with either NO donors or inhibitors of NO synthase had no effect
on RV-induced IL-8 elaboration measured either 6 or 24 h after virus challenge.
Nasal wash specimens from RV-infected volunteers contained low concentrations of
nitrite that were not different from the concentrations in specimens from sham
challenged subjects. The concentration of nitrite in these specimens did not
change over the course of the subjects' rhinoviral illness. These results suggest
that NO does not participate in the pathogenesis of RV infections.
PMID- 10194166
TI - Viruses and bacteria in bronchial samples from patients with primary
hypogammaglobulinemia.
AB - Viruses and bacteria in bronchoalveolar lavage fluids, protected specimen brush
samples, and bronchial biopsies from 14 patients with primary
hypogammaglobulinemia (11 patients with common variable immunodeficiency [CVID]
and three patients with X-linked agammaglobulinemia [XLA]) were analyzed. At the
time of the study, the patients had no signs of acute respiratory infections, and
no antibiotics were administered. In addition to routine bacterial and viral
cultures, polymerase chain reaction tests were used for the detection of
adenovirus, cytomegalovirus (CMV), herpes simplex virus 1, enterovirus,
rhinovirus, Borrelia burgdorferi, Chlamydia pneumoniae, Legionella spp.,
Mycoplasma pneumoniae, Pneumocystis carinii, and Ureaplasma urealyticum. Viruses
(four adenoviruses, one CMV, and one rhinovirus) were detected in four of the 11
(36%) CVID patients. No viruses were found in the three patients with XLA or in
13 control patients. Bacteria from the lower respiratory tract were detected in
nine of the 14 (64%) patients with hypogammaglobulinemia and three of the 13
(23%) control patients. Haemophilus influenzae was the most prevalent bacterium
(43%) in the hypogammaglobulinemia patients. The study shows that patients with
CVID harbor viral and bacterial infections in the lower respiratory tract, which
may predispose to the development of changes in the respiratory tract.
PMID- 10194167
TI - Selectin blockade prevents antigen-induced late bronchial responses and airway
hyperresponsiveness in allergic sheep.
AB - Antigen challenge can elicit an allergic inflammatory response in the airways
that involves eosinophils, basophils, and neutrophils and that is expressed
physiologically as a late airway response (LAR) and airway hyperresponsiveness
(AHR). Although previous studies have suggested that E-selectin participates in
these allergic airway responses, there is little information concerning the role
of L-selectin. To address this question, we examined the effects of administering
an L-selectin-specific monoclonal antibody, DU1-29, as well as three small
molecule selectin binding inhibitors, on the development of early airway
responses (EAR), LAR and AHR in allergic sheep undergoing airway challenge with
Ascaris suum antigen. Sheep treated with aerosol DU1-29 before antigen challenge
had a significantly reduced LAR and did not develop postchallenge AHR. No
protective effect was seen when sheep were treated with a nonspecific control
monoclonal antibody. Treatment with DU1-29 also reduced the severity of the EAR
to antigen. Similar results were obtained with each of the three small molecule
selectin inhibitors at doses that depended on their L-, but not necessarily E
selectin inhibitory capacity. The inhibition of the EAR with one of the
inhibitors, TBC-1269, was associated with a reduction in histamine release.
Likewise, treatment with TBC-1269 reduced the number of neutrophils recovered in
bronchoalveolar lavage (BAL) during the time of LAR and AHR. TBC-1269, given 90
min after antigen challenge also blocked the LAR and the AHR, but this protection
was lost if the treatment was withheld until 4 h after challenge, a result
consistent with the proposed time course of L-selectin involvement in leukocyte
trafficking. These are the first data indicating that L-selectin may have a
unique cellular function that modulates allergen-induced pulmonary responses.
PMID- 10194168
TI - Circulating leptin in patients with chronic obstructive pulmonary disease.
AB - Unexplained weight loss is common in patients with chronic obstructive pulmonary
disease (COPD). Since leptin, an obesity gene product, is known to play important
roles in the control of body weight and energy expenditure, we investigated serum
leptin levels, along with circulating tumor necrosis factor-alpha (TNF-alpha) and
soluble TNF receptor (sTNF-R55 and -R75) levels, in 31 patients with COPD and 15
age-matched healthy controls. The body mass index (BMI) and percent body fat
(%fat) were significantly lower in the COPD patients than in the healthy controls
(BMI = 18.1 +/- 2.7 kg/m2 versus 22.8 +/- 2.2 kg/m2 [mean +/- SD]; p < 0.0001;
%fat = 16.9 +/- 5.8% versus 24.3 +/- 4.9%; p < 0.001). Serum leptin levels were
significantly lower in the COPD patients than in the healthy controls (1.14 +/-
1.17 ng/ml versus 2.47 +/- 2.01 ng/ml; p < 0.05). In contrast, serum TNF-alpha
levels (6.59 +/- 1.92 pg/ml versus 5.41 +/- 1.60 pg/ml; p < 0.05), plasma sTNF
R55 (1.16 +/- 0.47 ng/ml versus 0.67 +/- 0.13 ng/ml; p < 0.0001) and sTNF-R75
(3.65 +/- 1.29 ng/ml versus 2.25 +/- 0.43 ng/ml; p < 0.0001) levels were
significantly higher in the COPD patients than in the healthy controls.
Importantly, circulating leptin levels (log transformed) did correlate well with
BMI and %fat, but not with TNF-alpha or with sTNF-R levels in the COPD patients.
These data suggest that circulating leptin is independent of the TNF-alpha system
and is regulated physiologically even in the presence of cachexia in patients
with COPD.
PMID- 10194169
TI - Independent and combined effects of inhaled nitric oxide, liquid
perfluorochemical, and high-frequency oscillatory ventilation in premature lambs
with respiratory distress syndrome.
AB - Acute lung injury caused by tidal volume ventilation in the premature lamb with
respiratory distress syndrome (RDS) is characterized by progessive deterioration
in gas exchange and lung inflammation. Inhaled nitric oxide (iNO) improves gas
exchange and decreases lung neutrophil accumulation in premature lambs with RDS.
Mechanical lung recruitment techniques such as high-frequency oscillatory
ventilation (HFOV) and partial liquid ventilation (PLV) also decrease lung injury
and improve gas exchange in experimental models of neonatal respiratory failure.
We hypothesized that two lung recruitment strategies (HFOV and PLV) would have
similar effects on gas exchange and lung inflammation, and would augment the
response to iNO. We studied the individual and combined effects of iNO, HFOV, and
PLV (perflubron) in 31 extremely premature lambs (115 d, 0.78 term) using seven
mechanical ventilation protocols. Four groups were treated with conventional
ventilation (control CV, CV + iNO, CV + PLV, and CV + PLV + iNO). Three groups
were treated with HFOV (control HFOV, HFOV + iNO, HFOV + PLV). Control CV animals
had progressive deterioration in gas exchange over the 4-h study period (a/AO2 at
4 h = 0.06 +/- 0.01). In contrast, both HFOV and CV + PLV caused sustained
improvements in oxygenation at 4 h (HFOV a/AO2 = 0. 27 +/- 0.06, CV + PLV a/AO2 =
0.25 +/- 0.04; p < 0.01 versus CV). Both lung recruitment strategies improved
oxygenation when combined with iNO (5 ppm). Lung neutrophil accumulation was
reduced by HFOV, PLV, and iNO compared to CV. We conclude that HFOV and PLV with
perflubron cause similar improvements in gas exchange and lung inflammation in
the premature lamb with severe RDS, and both strategies augment the oxygenation
response to iNO.
PMID- 10194170
TI - Different effects of inhaled aspirinlike drugs on allergen-induced early and late
asthmatic responses.
AB - Little is known about the anti-asthmatic effects of powerful anti-inflammatory
agents such as aspirin-like drugs. We compared the effects of two aspirin-like
drugs with different pharmacologic activities, sodium salicylate (SSA) and
indomethacin, with the effect of lysine acetylsalicylate (LASA), inhaled 30 min
before challenge, on the early and the late asthmatic response induced by a
single dose of allergen causing a 25% decrease in FEV1 in a preliminary
challenge. Inhaled SSA partially prevented both the early and late response,
providing a protection with respect to placebo of 22 +/- 6% in the early phase
and 23 +/- 9% in the late phase of the response. These values were lower (but not
significantly) than those of LASA (41 +/- 9% and 39 +/- 11%, respectively). In a
second group of patients, indomethacin failed to affect the early response, while
LASA provided a protection of 31 +/- 7%. However, these two drugs were equally
effective in reducing the late response (44 +/- 18% and 39 +/- 17% protection for
LASA and indomethacin, respectively). In subjects with an early response, despite
being ineffective in preventing allergen-induced bronchoconstriction,
indomethacin blocked the allergen-induced increase in bronchial
hyperresponsiveness measured 2 h after challenge. We conclude that inhaled
salicylates, but not indomethacin, exert a protective activity against the early
allergic response. This difference is not explained by the different pattern of
cyclooxygenase inhibitory activity of these drugs.
PMID- 10194171
TI - Severity of illness models for respiratory syncytial virus-associated
hospitalization.
AB - The objective of this investigation was to examine the feasibility of
multivariate severity of illness models for pediatric patients hospitalized with
respiratory syncytial virus (RSV) infection. From a preexisting retrospective
cohort study database, all infants and children 2 yr of age or younger with
community-acquired RSV infection admitted to the University of Michigan's C. S.
Mott Children's Hospital during nine epidemics were examined. The study group
consisted of 802 hospitalized patients younger than 2 yr of age with community
acquired RSV infection; 182 (23%) patients had prolonged hospital length of stay
defined as 7 d or greater. Multivariate logistic regression modeling of nine
variables measurable during the first hospital day was strongly associated with
prolonged hospitalization (p < 0.0001). Receiver operator characteristic curve
analysis resulted in an area under the curve of 0.894, indicating excellent model
discrimination. Goodness-of-fit testing indicated excellent model calibration for
observed versus predicted outcomes (p = 0.216). We conclude that severity of
illness models for RSV-associated hospitalization with excellent predictive
properties in terms of classification, discrimination, and calibration are
possible. Further study is required to determine if such models are generalizable
across multiple centers and epidemics.
PMID- 10194172
TI - Spontaneous breathing during ventilatory support improves ventilation-perfusion
distributions in patients with acute respiratory distress syndrome.
AB - Ventilation-perfusion (V A/Q) distributions were evaluated in 24 patients with
acute respiratory distress syndrome (ARDS), during airway pressure release
ventilation (APRV) with and without spontaneous breathing, or during pressure
support ventilation (PSV). Whereas PSV provides mechanical assistance of each
inspiration, APRV allows unrestricted spontaneous breathing throughout the
mechanical ventilation. Patients were randomly assigned to receive APRV and PSV
with equal airway pressure limits (Paw) (n = 12) or minute ventilation (V E) (n =
12). In both groups spontaneous breathing during APRV was associated with
increases (p < 0.05) in right ventricular end-diastolic volume, stroke volume,
cardiac index (CI), PaO2, oxygen delivery, and mixed venous oxygen tension (PvO2)
and with reductions (p < 0.05) in pulmonary vascular resistance and oxygen
extraction. PSV did not consistently improve CI and PaO2 when compared with APRV
without spontaneous breathing. Improved V A/Q matching during spontaneous
breathing with APRV was evidenced by decreases in intrapulmonary shunt (equal
Paw: 33 +/- 4 to 24 +/- 4%; equal V E: 32 +/- 4 to 25 +/- 2%) (p < 0.05), dead
space (equal Paw: 44 +/- 9 to 38 +/- 6%; equal V E: 44 +/- 9 to 38 +/- 6%) (p <
0.05), and the dispersions of ventilation (equal Paw: 0.96 +/- 0.23 to 0.78 +/-
0.22; equal V E: 0.92 +/- 0.23 to 0.79 +/- 0.22) (p < 0.05), and pulmonary blood
flow distribution (equal Paw: 0.89 +/- 0.12 to 0.72 +/- 0.10; equal V E: 0.94 +/-
0.19 to 0.78 +/- 0.22) (p < 0.05). PSV did not improve V A/Q distributions when
compared with APRV without spontaneous breathing. These findings indicate that
uncoupling of spontaneous and mechanical ventilation during APRV improves V A/Q
matching in ARDS presumably by recruiting nonventilated lung units. Apparently,
mechanical assistance of each inspiration during PSV is not sufficient to
counteract the V A/Q maldistribution caused by alveolar collapse in patients with
ARDS.
PMID- 10194173
TI - The attributable morbidity and mortality of ventilator-associated pneumonia in
the critically ill patient. The Canadian Critical Trials Group.
AB - To evaluate the attributable morbidity and mortality of ventilator-associated
pneumonia (VAP) in intensive care unit (ICU) patients, we conducted a
prospective, matched cohort study. Patients expected to be ventilated for > 48 h
were prospectively followed for the development of VAP. To determine the excess
ICU stay and mortality attributable to VAP, we matched patients with VAP to
patients who did not develop clinically suspected pneumonia. We also conducted
sensitivity analyses to examine the effect of different populations, onset of
pneumonia, diagnostic criteria, causative organisms, and adequacy of empiric
treatment on the outcome of VAP. One hundred and seventy-seven patients developed
VAP. As compared with matched patients who did not develop VAP, patients with VAP
stayed in the ICU for 4.3 d (95% confidence interval [CI]: 1.5 to 7. 0 d) longer
and had a trend toward an increase in risk of death (absolute risk increase:
5.8%; 95% CI: -2.4 to 14.0 d; relative risk (RR) increase: 32.3%; 95% CI: -20.6
to 85.1%). The attributable ICU length of stay was longer for medical than for
surgical patients (6. 5 versus 0.7 d, p < 0.004), and for patients infected with
"high risk" organisms as compared with "low risk" organisms (9.1 d versus 2.9 d).
The attributable mortality was higher for medical patients than for surgical
patients (RR increase of 65% versus -27.3%, p = 0. 04). Results were similar for
three different VAP diagnostic criteria. We conclude that VAP prolongs ICU length
of stay and may increase the risk of death in critically ill patients. The
attributable risk of VAP appears to vary with patient population and infecting
organism.
PMID- 10194174
TI - Long-term ambient air pollution and respiratory symptoms in adults (SAPALDIA
study). The SAPALDIA Team.
AB - The association between long-term exposure to ambient air pollution and
respiratory symptoms was investigated in a cross-sectional study in random
population samples of adults (aged 18 to 60 yr, n = 9,651) at eight study sites
in Switzerland. Information on respiratory symptoms was obtained with an extended
version of the European Community Respiratory Health Survey questionnaire. The
impact of annual mean concentrations of air pollutants was analyzed separately
for never-, former, and current smokers. After controlling for age, body mass
index, gender, parental asthma, parental atopy, low education, and foreign
citizenship, we found positive associations between annual mean concentrations of
NO2, total suspended particulates, and particulates of less than 10 micrometers
in aerodynamic diameter (PM10) and reported prevalences of chronic phlegm
production, chronic cough or phlegm production, breathlessness at rest during the
day, breathlessness during the day or at night, and dyspnea on exertion. We found
no associations with wheezing without cold, current asthma, chest tightness, or
chronic cough. Among never-smokers, the odds ratio (95% confidence interval) for
a 10 micrograms/ m3 increase in the annual mean concentration of PM10 was 1. 35
(1.11 to 1.65) for chronic phlegm production, 1.27 (1.08 to 1.50) for chronic
cough or phlegm production, 1.48 (1.23 to 1.78) for breathlessness during the
day, 1.33 (1.14 to 1.55) for breathlessness during the day or at night, and 1.32
(1.18 to 1.46) for dyspnea on exertion. No associations were found with annual
mean concentrations of O3. Similar associations were also found for former and
current smokers, except for chronic phlegm production. The observed associations
remained stable when further control was applied for environmental tobacco smoke
exposure, past and current occupational exposures, atopy, and early childhood
respiratory infections when restricting the analysis to long-term residents and
to non- alpine areas, and when excluding subjects with physician-diagnosed
asthma. The high correlation between the pollutants makes it difficult to sort
out the effect of one single pollutant. This study provides further evidence that
long-term exposure to air pollution of rather low levels is associated with
higher prevalences of respiratory symptoms in adults.
PMID- 10194175
TI - Reversible and irreversible airflow obstruction as predictor of overall mortality
in asthma and chronic obstructive pulmonary disease.
AB - The importance of reversible airflow obstruction to the prognosis of asthma and
chronic obstructive pulmonary disease (COPD) is not clear. We tested the
hypothesis that reversibility to corticosteroid and bronchodilator is not an
independent predictor of prognosis, but merely reflects a component of the
maximal attainable lung function, which is the best spirometric predictor of
survival. During a 6-yr period (1983-1988), 1,586 subjects with asthma or COPD
underwent standardized bronchodilator and corticosteroid reversibility tests at a
chest clinic in Copenhagen. The vital status was obtained by September 1997. The
relationship between mortality and age, gender, smoking, FEV1, and
reversibilities was examined by Cox proportional hazards analyses. Of 1,586
subjects, 850 had died before September 1997. Age, smoking, and FEV1 were
significant predictors of mortality. After controlling for baseline FEV1,
bronchodilator and corticosteroid reversibility were significantly associated
with better survival. However, after controlling for best FEV1 all
reversibilities became nonsignificant and nonpredictive. The combined use of
corticosteroid and bronchodilator reversibility in survival analyses is a novel
approach, and we have shown that both contribute to survival prediction to the
extent that they modify FEV1. However, reversibility per se does not influence
survival in subjects with moderate to severe asthma or COPD.
PMID- 10194176
TI - Inhibition of bronchoprotective effects of beta2-adrenoceptor agonists by
peroxynitrite in guinea pig airways.
AB - Peroxynitrite plays an important role in the pathogenesis of inflammatory
diseases, including those affecting the lung. In inflamed airways, simultaneous
cellular production of superoxide anion (.O2-) and nitric oxide (NO) may occur,
potentially resulting in continuous formation of peroxynitrite. However, because
peroxynitrite has a short half-life, its in vivo physiologic effects in the
airways may not be sufficiently evaluated with a single administration.
Accordingly, this study was designed to use 3-morpholinosydnonimine (SIN-1), a
compound that releases peroxynitrite, to determine whether peroxynitrite could
alter airway beta2-adrenoceptor (beta2-AR) function in anesthetized guinea pigs.
Though SIN-1(10(-)7 M) alone had no effect on pulmonary resistance, pretreatment
with SIN-1 significantly attenuated isoprenaline- and salbutamol-induced
bronchoprotection against acetylcholine. Pretreatment with SIN-1 also attenuated
forskolin-induced bronchoprotection. S-Nitroso-N-acetylpenicillamine (SNAP), a
potent NO donor, did not have the same effect as SIN-1. N-Acetylcysteine and
glutathione each significantly reversed the inhibitory effect of SIN-1 on
isoprenaline-induced bronchoprotection in a dose-dependent manner. These striking
findings suggested that peroxynitrite, but not NO, is an important mediator of
alteration of beta2-AR function in airway smooth muscle. Additionally, the action
of peroxynitrite seems to be directed either at adenylate cyclase activity or at
effects downstream of such activity.
PMID- 10194177
TI - Cardiopulmonary exercise testing before and after lung and heart-lung
transplantation.
AB - Heart-lung (HLT) and lung transplantation (LT) have been shown to be effective
procedures for patients with end-stage cardiopulmonary disorders. As yet, few
data exist on the exercise performance of patients before and after thoracic
transplantation except with regard to 6-min walk tests. In this article we report
cardiopulmonary exercise test results of lung and heart-lung transplant
recipients in comparison with their pretransplant values. We studied 103
consecutive recipients of single-lung (n = 46), bilateral lung (n = 32), and
heart-lung (n = 25) transplants. Cardiopulmonary exercise testing with a cycle
ergometer was performed before and shortly after surgery. Before transplantation,
all patients showed severe exercise intolerance and markedly impaired parameters
reflecting cardiopulmonary function (e.g., work capacity: 20 +/- 11% predicted;
oxygen uptake: 34 +/- 12% predicted; oxygen pulse: 50 +/- 18% predicted;
functional dead space ventilation: 57 +/- 10% of minute ventilation; alveolar
arterial oxygen difference during exercise: 79 +/- 15 mm Hg). At 55 +/- 9 d after
transplantation, transplant recipients reached maximum oxygen uptakes in the
range of 22 to 71% of predicted values; the peak oxygen uptake was increased
after transplantation (13.1 +/- 3.4 ml/min/kg versus 10.4 +/- 3.8 ml/min/kg; p <
0.001). Work capacity, oxygen pulse, tidal volume, and peak minute ventilation
did not differ in patients following single- or double-lung tranplantation or
HLT. Ventilatory factors did not appear to limit exercise capacity in any group.
Despite the persistent limitations in aerobic capacity and work rate seen in many
of the recipients, cardiopulmonary performance is reasonably well restored
shortly after LT and HLT.
PMID- 10194178
TI - Exhaled nitric oxide concentrations during treatment of wheezing exacerbation in
infants and young children.
AB - While it is known that exhaled nitric oxide (ENO) is increased in adults and
school children with asthma exacerbation probably as an expression of disease
activity, no studies have investigated whether this phenomenon also occurs in
infants and young children with recurrent wheeze exacerbation. We measured ENO in
13 young children (mean age 20.2 mo) with recurrent wheeze (Group 1) during an
acute episode and after 5 d of oral prednisone therapy. ENO was measured also in
nine healthy control subjects (Group 2) (mean age 16.9 mo) and in six children
with a first-time viral wheezy episode (Group 3) (mean age 11 mo). To measure
ENO, infants inhaled NO-free air via a face mask from a reservoir and, through a
nonrebreathing valve, exhaled in a collecting bag that was analyzed by
chemiluminescence. To address the question of whether the levels of ENO collected
in the bag are a reflection of the pulmonary airway, ENO determinations were
performed in two healthy infants before and after tracheal intubation for
elective surgery. During the acute episode of wheezing the mean (+/- SEM) value
of ENO in children with recurrent wheeze (Group 1) was 14.1 +/- 1.8 ppb, almost
threefold higher than in healthy control subjects (5.6 +/- 0.5 ppb, p < 0.001).
After steroid therapy we found a mean fall of 52% in ENO (5.9 +/- 0.7 ppb, p <
0.01) compared with baseline values. ENO values measured before and after
intubation in two infants were 6 ppb and 5 ppb in one child and 7 ppb and 6 ppb
in the other one. The mean value of ENO of children with first-time wheeze (Group
3) was 8.3 +/- 1.3 ppb, significantly lower (p < 0.05) than the value of children
with recurrent wheeze (Group 1). In conclusion, we describe a method to measure
ENO in young children and show that infants with recurrent wheeze have elevated
levels of ENO during exacerbation that rapidly decrease after steroid therapy.
This suggests that, in these children, airway inflammation could be present at a
very early stage.
PMID- 10194179
TI - Isocapnic hyperpnea accelerates carbon monoxide elimination.
AB - A major impediment to the use of hyperpnea in the treatment of CO poisoning is
the development of hypocapnia or discomfort of CO2 inhalation. We examined the
effect of nonrebreathing isocapnic hyperpnea on the rate of decrease of
carboxyhemoglobin levels (COHb) in five pentobarbital-anesthetized ventilated
dogs first exposed to CO and then ventilated with room air at normocapnia
(control). They were then ventilated with 100% O2 at control ventilation, and at
six times control ventilation without hypocapnia ("isocapnic hyperpnea") for at
least 42 min at each ventilator setting. We measured blood gases and COHb. At
control ventilation, the half-time for elimination of COHb (t1/2) was 212 +/- 17
min (mean +/- SD) on room air and 42 +/- 3 min on 100% O2. The t1/2 decreased to
18 +/- 2 min (p < 0.0005) during isocapnic hyperpnea. In two similarly prepared
dogs treated with hyperbaric O2, the t1/2 were 20 and 28 min. We conclude that
isocapnic hyperpnea more than doubles the rate of COHb elimination induced by
normal ventilation with 100% O2. Isocapnic hyperpnea could improve the efficacy
of the standard treatment of CO poisoning, 100% O2 at atmospheric or increased
pressures.
PMID- 10194180
TI - Baroreflex control of heart rate in a canine model of obstructive sleep apnea.
AB - We have recently demonstrated the development of systemic hypertension in a
canine model of obstructive sleep apnea (OSA), but the underlying physiological
mechanisms were not identified. Therefore, the purpose of this study was to
examine the effect of OSA on arterial baroreceptor control of heart rate (HR) in
this canine model. OSA was produced in three dogs for 1 to 3 mo. Baroreflex
control of HR was determined with graded infusions of vasoactive agents
(phenylephrine and nitroprusside) administered over 30 to 60 s, during which
steady-state systolic blood pressure (BP) and cardiac R-R interval responses were
recorded. BP was measured with a permanently implanted arterial catheter and a
telemetry system. Although, as previously reported, OSA resulted in increases in
daytime (awake) mean BP of 6.0 to 26.8 mm Hg, there was no change in daytime
baseline HR or in the slope of the systolic BP-R-R interval curve (p > 0.2). The
findings demonstrate that OSA in the dog is associated with resetting of the
baroreceptors to a higher pressure, but no change in baroreflex sensitivity.
PMID- 10194182
TI - LPS challenge in D-galactosamine-sensitized mice accounts for caspase-dependent
fulminant hepatitis, not for septic shock.
AB - Experimental models of sepsis using endotoxin challenges, including studies with
sensitized animals with D-galactosamine, have largely contributed to the basic
rationale for innovative clinical trials in human septic shock, which have, to
date, failed. The ability of these models to reproduce human disease has been
highly discussed. We report here that the widely used D-galactosamine/LPS model
does not account for septic shock. Treatment with YVAD-CMK, a potent tetrapeptide
inhibitor of caspases of the interleukin (IL)-1beta converting enzyme (ICE)
family, protects from LPS-induced liver apoptosis and mortality in D
galactosamine-sensitized mice when administered either before or up to 2 h after
the lethal challenge. This curative effect is related to complete inhibition of
caspase-3 activity in the liver. However, YVAD-CMK does not affect LPS-induced
release of IL-1beta and does not protect from a lethal dose of LPS in
unsensitized mice. These experiments demonstrate the difference between these two
widely recognized experimental models of sepsis. LPS toxicity in D-galactosamine
treated mice, leading to blocked gene transcription, results from tumor necrosis
factor (TNF)-alpha-induced caspase-3-dependent liver injury, not from the
systemic inflammatory response. These results provide evidence that inhibitors of
the ICE caspase family can prevent or even overcome the ongoing hepatic injury
induced by TNF-alpha during sepsis, ischemia-reperfusion, or severe hepatitis.
PMID- 10194181
TI - Contribution of 92 kDa gelatinase/type IV collagenase in bronchial inflammation
during status asthmaticus.
AB - In order to assess inflammatory features related to severe asthma as compared
with mild asthma, we investigated the secretion of 92 kDa gelatinase matrix
metalloproteinase (MMP-9) in bronchial lavages of six patients undergoing
mechanical ventilation (MV) for status asthmaticus (SA) and in six patients with
mild asthma. Ten healthy nonventilated patients and four patients under MV
without preexisting respiratory disease were also investigated. Patients with SA
were characterized by prominent neutrophilic inflammation (82 +/- 4% versus 10%
in mild asthma). On the basis of enzymatic and immunological analysis, results
showed an acute 10- to 160-fold increase of 92 kDa gelatinase (MMP-9)
concentration in epithelial lining fluid (ELF) from patients with SA, together
with activated forms (46 and 26 kDa) of stromelysin-1 matrix metalloproteinase
(MMP-3) and detectable concentration of free metallogelatinolytic activity (1-5
micrograms gelatin hydrolyzed/48 h/ml ELF). Concomitant elevated level of tissue
inhibitor of metalloproteinase-1 (TIMP-1) was shown only in patients with SA,
thus counterbalancing, at least partially, excess of activated 92 kDa gelatinase.
Acutely enhanced albumin levels were only observed in patients with SA; in
addition, 92 kDa gelatinase and albumin levels were significantly and positively
correlated (r = 0.96, p < 0.0001), suggesting that 92 kDa gelatinase may account
for increased bronchial permeability in patients with SA. Several arguments
support that 92 kDa gelatinase during SA originates both from numerous activated
chemoattracted neutrophils and from activated bronchial epithelial cells in
response to in situ lung injury. The fact that no relevant change in ELF,
albumin, MMP-9, MMP-3, TIMP-1, or laminin degradation products was observed
during mild asthma, strongly supports that the mechanism of airway inflammation
in SA is quite distinct from that observed in mild asthma.
PMID- 10194183
TI - Common respiratory viruses in lower airways of patients with acute
hypersensitivity pneumonitis.
AB - Hypersensitivity pneumonitis (HP), a lung disease with "flulike" symptoms,
results from repeated exposures to well defined, nonpathogenic antigens. This
study examined whether respiratory viruses are present in the lower airways, the
likely site of hypersensitivity reaction, in patients with HP. The polymerase
chain reaction (PCR) method was used to test for 10 common respiratory viruses in
bronchoalveolar lavage (BAL) cells obtained from patients with acute HP and from
unexposed healthy volunteers. Immunocytochemistry was subsequently used to
localize viral proteins within BAL cells. The results of PCR showed that
influenza A virus was the most frequently detected virus in the BAL cells of our
study patients (six of 13) and control subjects (two of six). Influenza A
proteins were detected within alveolar macrophages in nine of 13 patients and in
two of six control subjects. The number of total BAL cells, but not lymphocytes,
was higher in patients with documented influenza A proteins than in patients with
no influenza A proteins (p = 0.017) and correlated with the proportion of
influenza-A-positive alveolar macrophages (r = 0.7; p = 0.036). This report
documents the presence of viruses in the lower airways of patients with acute HP.
The findings may imply a potential role for influenza A in the modulation of HP
during antigen exposure.
PMID- 10194184
TI - Activation of NF-kappaB in Mycobacterium tuberculosis- induced interleukin-2
receptor expression in mononuclear phagocytes.
AB - Soluble interleukin-2 receptor-alpha (IL-2Ralpha) has been reported to be
increased in the sera of patients with advanced tuberculosis, and levels decline
after therapy in accordance with improvement of radiologic findings. We
investigated expression of the IL-2Ralpha in bronchoalveolar lavage (BAL) cells
in active pulmonary tuberculosis, and evaluated the mechanism Mycobacterium
tuberculosis induces in the IL-2Ralpha using the THP-1 mononuclear phagocyte cell
line. We found IL-2Ralpha expression to be increased in BAL cells from involved
sites of active pulmonary tuberculosis. Expression of the alpha-chain of IL
2Ralpha on peripheral blood monocytes (PBM) was induced by M. tuberculosis by
flow cytometry evaluation. Northern analysis demonstrated increased IL-2Ralpha
gene expression after stimulation with M. tuberculosis which was further induced
by interferon-gamma (IFN-gamma). The IL-2Ralpha promoter containing the nuclear
factor kappa B (NF-kappaB) site was transcriptionally induced by M. tuberculosis
and this NF-kappaB site could confer inducibility to a heterologous herpes
thymidine kinase (TK) promoter by M. tuberculosis. Electrophoretic mobility shift
assays (EMSAs) revealed specific binding of nuclear protein to the NF-kappaB site
upon induction with M. tuberculosis. Using antibodies against the p50 and p65
subunits of NF-kappaB in EMSAs, the involvement of both p50 and p65 proteins was
further demonstrated. Functional expression of the IL-2Ralpha on mononuclear
phagocytes in M. tuberculosis infection may play an important immunomodulatory
role in the host response.
PMID- 10194185
TI - Localization of TFF3, a new mucus-associated peptide of the human respiratory
tract.
AB - Trefoil factor family (TFF)-domain peptides (formerly P-domain peptides, trefoil
factors) represent major mucin-associated peptides of the gastrointestinal tract.
Here, the first localization studies on TFF3 in the lower respiratory tract of
human material are presented. Immunohistochemistry revealed significant
accumulation of TFF3 to mucous cells in the acini of submucosal glands and
varying amounts in goblet cells at the ductular portions and the surface
epithelium. TFF3 appears also as a component of the mucus, for example from
patients with chronic bronchitis. Expression of TFF3 was also shown by use of the
polymerase chain reaction. In contrast, TFF1 and TFF2 transcripts were hardly
detectable in the human respiratory tract. Thus, a structural function of TFF3
for the airway mucus is discussed, possibly together with the mucins MUC5B and
MUC5AC.
PMID- 10194186
TI - The detection of Epstein-Barr virus DNA in lung tissue from patients with
idiopathic pulmonary fibrosis.
AB - Idiopathic pulmonary fibrosis (IPF) is a clinical syndrome in which the
precipitating factors are unclear. An association between Epstein-Barr Virus
(EBV) and IPF had previously been suggested using serology and
immunohistochemistry. This study sought confirmation of the presence of EBV DNA
in the lung tissue of patients with IPF. Lung tissue obtained surgically from 27
patients with IPF and 28 control subjects was investigated for the presence of
EBV by immunohistochemistry and polymerase chain reaction (PCR) analysis.
Immunohistochemistry used antibodies specific for EBV lytic cycle antigens
(gp340/220 and VCA). Nested PCR analysis used oligonucleotide primers specific
for EBV and was sensitive to one copy of EBV DNA. Twelve of the 27 patients with
IPF (44%) and three of the 28 control subjects (10%) were EBV positive by
immunohistochemistry (p = 0.005). Thirteen of the patients with IPF (48%) and
four of the control subjects (14%) were EBV positive by PCR (p = 0.007). Eleven
of the patients with IPF (41%) and none of the control subjects were EBV positive
by both immunohistochemistry and PCR (p = < 0.001). These data further suggest an
association between EBV and IPF. In addition it defines a novel method for
detecting EBV in lung tissue. EBV may be involved in the pathogenesis of the
disease; however, further studies are required to establish a causal
relationship.
PMID- 10194187
TI - Angiotensin-1 converting enzyme polymorphisms in chronic beryllium disease.
AB - To test the hypothesis that the angiotensin converting enzyme (ACE) genotype is
associated with chronic beryllium disease (CBD) and disease severity, we studied
50 cases of CBD and compared their ACE genotype to that of two different control
groups, consisting of: (1) 50 participants from a beryllium machining facility;
and (2) 50 participants from a non-beryllium-associated workplace. We found no
statistically significant difference in the frequency of the I or D allele or of
the DD genotype among cases of CBD and either control group. The odds ratio (OR)
for the CBD DD genotype as compared with the non-DD genotype was 1.58 (95%
confidence interval [CI]: 0.68 to 3.66, p = 0.12) for the beryllium-exposed
control group, and 1.09 (95% CI: 0.48 to 2.46, p = 0.56) for the non-beryllium
exposed controls. We found an association between serum ACE activity and the ACE
genotype, with DD cases having the highest median serum ACE activity (p = 0.005).
We evaluated the beryllium lymphocyte proliferation test (BeLPT), bronchoalveolar
lavage (BAL) cell components, chest radiography, pulmonary function test results,
and exercise physiology in our CBD cases. No statistically significant
associations with these disease markers were found for the CBD cases with the DD
genotype. Although the difference was not statistically significant, the DD cases
had a shorter median duration of exposure to beryllium before diagnosis of CBD,
and tended to have a weaker response in their blood and BAL BeLPT than did the
non-DD cases. These findings may indicate that the ACE genotype is important in
the immune response to beryllium and in progression to beryllium disease.
PMID- 10194188
TI - Does snoring contribute to presbycusis?
AB - It is well known that hearing acuity decreases with age. The precise mechanism
responsible for this phenomenon, called presbycusis, is unknown. One hypothesis
advanced to explain this loss of acuity implicates chronic exposure to snoring
noise. Consequently, the purpose of this study was to investigate whether snoring
is associated with hearing loss. We examined 219 patients (63 women and 156 men)
referred to our sleep disorders center. All of the patients underwent nocturnal
polysomnography with measurements of snoring, as well as standard audiometry
(i.e., measurement of hearing thresholds at 250 Hz, 500 Hz, 1 kHz, 2 kHz, 3 kHz,
4 kHz, 6 kHz, and 8 kHz). Snoring was quantified by measuring three parameters:
snoring index (SI = number of snores/h of sleep), average nocturnal sound
intensity (dBav), and maximum nocturnal sound intensity (dBmax). We used simple
correlation analysis to investigate the relationship between snoring and hearing
thresholds; multiple linear regression analysis to determine individual
contributions of age, sex, and snoring to the variability in hearing thresholds;
and comparison tests to determine whether mild snorers had less hearing
impairment than severe snorers. None of these statistical tests demonstrated that
snoring was a significant determinant of hearing. We conclude that snoring is not
associated with hearing loss and is therefore unlikely to account for
presbycusis.
PMID- 10194189
TI - Skeletal muscle dysfunction in chronic obstructive pulmonary disease. A statement
of the American Thoracic Society and European Respiratory Society.
PMID- 10194190
TI - Interaction of factors determining oxygen uptake at the onset of exercise.
AB - Considerable debate surrounds the issue of whether the rate of adaptation of
skeletal muscle O2 consumption (QO2) at the onset of exercise is limited by 1)
the inertia of intrinsic cellular metabolic signals and enzyme activation or 2)
the availability of O2 to the mitochondria, as determined by an extrinsic inertia
of convective and diffusive O2 transport mechanisms. This review critically
examines evidence for both hypotheses and clarifies important limitations in the
experimental and theoretical approaches to this issue. A review of biochemical
evidence suggests that a given respiratory rate is a function of the net drive of
phosphorylation potential and redox potential and cellular mitochondrial PO2
(PmitoO2). Changes in both phosphorylation and redox potential are determined by
intrinsic metabolic inertia. PmitoO2 is determined by the extrinsic inertia of
both convective and diffusive O2 transport mechanisms during the adaptation to
exercise and the rate of mitochondrial O2 utilization. In a number of exercise
conditions, PmitoO2 appears to be within a range capable of modulating muscle
metabolism. Within this context, adjustments in the phosphate energy state of the
cell would serve as a cytosolic "transducer," linking ATP consumption with
mitochondrial ATP production and, therefore, O2 consumption. The availability of
reducing equivalents and O2 would modulate the rate of adaptation of QO2.
PMID- 10194191
TI - Invited editorial on "Kinetics of absorption atelectasis during anesthesia: a
mathematical model"
PMID- 10194192
TI - Kinetics of absorption atelectasis during anesthesia: a mathematical model.
AB - Recent computed tomography studies show that inspired gas composition affects the
development of anesthesia-related atelectasis. This suggests that gas absorption
plays an important role in the genesis of the atelectasis. A mathematical model
was developed that combined models of gas exchange from an ideal lung
compartment, peripheral gas exchange, and gas uptake from a closed collapsible
cavity. It was assumed that, initially, the lung functioned as an ideal lung
compartment but that, with induction of anesthesia, the airways to dependent
areas of lung closed and these areas of lung behaved as a closed collapsible
cavity. The main parameter of interest was the time the unventilated area of lung
took to collapse; the effects of preoxygenation and of different inspired gas
mixtures during anesthesia were examined. Preoxygenation increased the rate of
gas uptake from the unventilated area of lung and was the most important
determinant of the time to collapse. Increasing the inspired O2 fraction during
anesthesia reduced the time to collapse. Which inert gas (N2 or N2O) was breathed
during anesthesia had minimal effect on the time to collapse.
PMID- 10194193
TI - Chronic exposure to nicotine alters endothelium-dependent arteriolar dilatation:
effect of superoxide dismutase.
AB - The first goal of this study was to determine whether chronic injection of
nicotine alters endothelium-dependent arteriolar dilatation. We measured the
diameter of cheek pouch resistance arterioles (approximately 50 microm in
diameter) in response to endothelium-dependent (acetylcholine and ADP) and
independent (nitroglycerin) agonists in control hamsters and hamsters treated
with nicotine (2 microg. kg-1. day-1 for 2-3 wk). In control hamsters,
acetylcholine (0.1 and 1.0 microM) dilated arterioles by 13 +/- 2 and 31 +/- 3%,
respectively, and ADP (1.0 and 10 microM) dilated arterioles by 18 +/- 1 and 30
+/- 1%, respectively. In contrast, acetylcholine (0.1 and 1.0 microM) dilated
arterioles by only 5 +/- 2 and 12 +/- 3%, respectively, and ADP (1.0 and 10
microM) dilated arterioles by only 7 +/- 2 and 13 +/- 3%, respectively, in
animals treated with nicotine (P < 0.05 vs. response in control hamsters).
Nitroglycerin produced similar dose-related dilatation of cheek pouch arterioles
in control and nicotine-treated hamsters. Our second goal was to examine a
possible mechanism for impaired endothelium-dependent arteriolar dilatation
during chronic treatment with nicotine. We found that superfusion of the cheek
pouch microcirculation with superoxide dismutase (150 U/ml) restored impaired
endothelium-dependent, but did not alter endothelium-independent, arteriolar
dilatation in hamsters treated with nicotine. Superfusion with superoxide
dismutase did not alter endothelium-dependent or -independent arteriolar
dilatation in control hamsters. We suggest that chronic exposure to nicotine
produces selective impairment of endothelium-dependent arteriolar dilatation via
a mechanism related to the synthesis/release of oxygen-derived free radicals.
PMID- 10194194
TI - Pulmonary perfusion is more uniform in the prone than in the supine position:
scintigraphy in healthy humans.
AB - The main purpose of this study was to find out whether the dominant dorsal lung
perfusion while supine changes to a dominant ventral lung perfusion while prone.
Regional distribution of pulmonary blood flow was determined in 10 healthy
volunteers. The subjects were studied in both prone and supine positions with and
without lung distension caused by 10 cmH2O of continuous positive airway pressure
(CPAP). Radiolabeled macroaggregates of albumin, rapidly trapped by pulmonary
capillaries in proportion to blood flow, were injected intravenously. Tomographic
gamma camera examinations (single-photon-emission computed tomography) were
performed after injections in the different positions. All data acquisitions were
made with the subject in the supine position. CPAP enhanced perfusion differences
along the gravitational axis, which was more pronounced in the supine than prone
position. Diaphragmatic sections of the lung had a more uniform pulmonary blood
flow distribution in the prone than supine position during both normal and CPAP
breathing. It was concluded that the dominant dorsal lung perfusion observed when
the subjects were supine was not changed into a dominant ventral lung perfusion
when the subjects were prone. Lung perfusion was more uniformly distributed in
the prone compared with in the supine position, a difference that was more marked
during total lung distension (CPAP) than during normal breathing.
PMID- 10194195
TI - External thoracic restriction, respiratory sensation, and ventilation during
exercise in men.
AB - Multiple factors may contribute to the dyspnea associated with restrictive
ventilatory disease (RVD). Simple models that examine specific features of this
problem are likely to provide insight into the mechanisms. Previous models of RVD
utilizing elastic loads may not represent completely the impact on pulmonary and
chest wall receptors derived from breathing at low thoracic volumes. The purpose
of this study was to investigate the sensory consequences of breathing at low
lung volumes induced by external thoracic restriction in an attempt to further
elucidate the etiology of dyspnea in this setting. Ten men were studied, with and
without an inelastic corset applied at residual volume (restriction resulted in
mean reductions in vital capacity, functional residual capacity, residual volume,
and forced expired volume in 1 s of 44, 31, 12.5, and 42%, respectively). During
10-min steady-state exercise tests (at a workload set to achieve approximately
65% maximum heart rate), restriction resulted in significant increases, compared
with control, in minute ventilation (61 vs. 49 l/min), respiratory frequency (43
vs. 23 breaths/min), and visual analog scale measurements of respiratory
discomfort (65 vs. 20 mm). Alveolar hyperventilation (end-tidal PCO2 = 39 vs. 44
Torr for control) and mild O2 desaturation (arterial blood O2 saturation = 93 vs.
95% for control) occurred. Hypoxemia, atelectasis, increased work and effort of
breathing, or a decrease in the volume-related feedback from chest wall and/or
lungs could be responsible for the increased dyspnea reported. External thoracic
restriction provides a useful model to study mechanisms of dyspnea in RVD.
PMID- 10194196
TI - Role of L-selectin in physiological manifestations after burn and smoke
inhalation injury in sheep.
AB - The effects of a monoclonal antibody against L-selectin [leukocyte adhesion
molecule (LAM)1-3] on microvascular fluid flux were determined in conscious sheep
subjected to a combined injury of 40% third-degree burn and smoke inhalation.
This combined injury induced a rapid increase in systemic prefemoral lymph flow
(sQlymph) from the burned area and a delayed-onset increase in lung lymph flow.
The initial increase in sQlymph was associated with an elevation of the lymph-to
plasma oncotic pressure ratio; consequently, it leads to a predominant increase
in the systemic soft tissue permeability index (sPI). In an untreated control
group, the increased sPI was sustained beyond 24 h after injury. Pretreatment
with LAM1-3 resulted in earlier recovery from the increased sPI, although the
initial responses in sQlymph and sPI were identical to those in the nontreatment
group. The delayed-onset lung permeability changes were significantly attenuated
by pretreatment with LAM1-3. These findings indicate that both leukocyte
dependent and -independent mechanisms are involved in the pathogenesis that
occurs after combined injury with burn and smoke inhalation.
PMID- 10194197
TI - Combined inhaled nitric oxide and inhaled prostacyclin during experimental
chronic pulmonary hypertension.
AB - Inhaled nitric oxide (NO) and inhaled prostacyclin (PGI2) produce selective
reductions in pulmonary vascular resistance (PVR) through differing mechanisms.
NO decreases PVR via cGMP, and PGI2 produces pulmonary vasodilation via cAMP. As
a general pharmacological principle, two drugs that produce similar effects via
different mechanisms should have additive or synergistic effects when combined.
We designed this study to investigate whether combined inhaled NO and PGI2
therapy results in additive effects during chronic pulmonary hypertension in the
rat. Monocrotaline injected 4 wk before study produced pulmonary hypertension in
all animals. Inhaled NO (20 parts/million) reversibly and selectively decreased
pulmonary artery pressure (Ppa) with a mean reduction of 18%. Four concentrations
of PGI2 were administered via inhalation (5, 10, 20, and 80 microg/ml), both
alone and combined with inhaled NO. Inhaled PGI2 alone decreased Ppa in a dose
dependent manner with no change in mean systemic arterial pressure. Combined
inhaled NO and PGI2 selectively and significantly decreased Ppa more did than
either drug alone. The effects were additive at the lower concentrations of PGI2
(5, 10, and 20 microg/ml). The combination of inhaled NO and inhaled PGI2 may be
useful in the management of pulmonary hypertension.
PMID- 10194198
TI - Airway hyperresponsiveness to ultrasonically nebulized distilled water in
subjects with tetraplegia.
AB - The majority of otherwise healthy subjects with chronic cervical spinal cord
injury (SCI) demonstrate airway hyperresponsiveness to aerosolized methacholine
or histamine. The present study was performed to determine whether ultrasonically
nebulized distilled water (UNDW) induces airway hyperresponsiveness and to
further elucidate potential mechanisms in this population. Fifteen subjects with
SCI, nine with tetraplegia (C4-7) and six with paraplegia (T9-L1), were initially
exposed to UNDW for 30 s; spirometry was performed immediately and again 2 min
after exposure. The challenge continued by progressively increasing exposure time
until the forced expiratory volume in 1 s decreased 20% or more from baseline
(PD20) or the maximal exposure time was reached. Five subjects responding to UNDW
returned for a second challenge 30 min after inhalation of aerosolized
ipratropium bromide (2.5 ml of a 0.6% solution). Eight of nine subjects with
tetraplegia had significant bronchoconstrictor responses to UNDW (geometric mean
PD20 = 7.76 +/- 7.67 ml), whereas none with paraplegia demonstrated a response
(geometric mean PD20 = 24 ml). Five of the subjects with tetraplegia who
initially responded to distilled water (geometric mean PD20 = 5.99 +/- 4.47 ml)
were not responsive after pretreatment with ipratropium bromide (geometric mean
PD20 = 24 ml). Findings that subjects with tetraplegia are hyperreactive to UNDW,
a physicochemical agent, combined with previous observations of hyperreactivity
to methacholine and histamine, suggest that overall airway hyperresponsiveness in
these individuals is a nonspecific phenomenon similar to that observed in
patients with asthma. The ability of ipratropium bromide to completely block UNDW
induced bronchoconstriction suggests that, in part, airway hyperresponsiveness in
subjects with tetraplegia represents unopposed parasympathetic activity.
PMID- 10194199
TI - V(O2) recovery kinetics in the horse following moderate, heavy, and severe
exercise.
AB - At the onset of exercise, horses exhibit O2 uptake (VO2) kinetics that are
qualitatively similar to those of humans. In humans, there is a marked
dissymmetry between on- and off-kinetics for VO2. This investigation sought to
formally characterize the off-transient (recovery) VO2 kinetics in the horse
within the moderate (M), heavy (H), and severe (S) exercise domains. Six horses
were run on a high-speed treadmill at M, H, and S exercise intensities (i.e.,
that speed which yielded approximately 50, 85, 100% peak VO2, respectively, on
the maximal incremental test). The time courses for the recovery were modeled by
using a three-phase model with a single-exponential (fast component) or double
exponential (fast and slow component) phase 2. The single-exponential phase 2
model provided an excellent fit to the off-transient data, with the exception of
one horse in the H domain which was best modeled by a double exponential. The
time delay elicited no domain dependency (M, 18.0 +/- 1.0; H, 17.6 +/- 1.1; S,
17.8 +/- 2.0 s; P > 0.05), as was the case for the fast-component time constants
(M, 16.3 +/- 2.0 s; H, 13.5 +/- 1.0 s; S, 14.6 +/- 0.3 s; P > 0.05). In the H and
S (but not M) domains, the VO2 following resolution of the fast component was
elevated above the preexercise baseline (H, 3.0 +/- 1.0 l/min; S, 5.7 +/- 1.1
l/min). This additional postexercise VO2 was correlated to the end-exercise
increase in lactate (r = 0.94, P < 0.001) but not the end-exercise pulmonary
arterial blood temperature (r = 0.45, P > 0.05). These data indicate that the
time delay and subsequent kinetic response of the primary (fast-component) phase
of exercise VO2 recovery in the horse is independent of the preceding exercise
intensity domain. However, in the H and S domains, the fast component resolves to
an elevated baseline.
PMID- 10194200
TI - Myogenic and vasoconstrictor responsiveness of skeletal muscle arterioles is
diminished by hindlimb unloading.
AB - The purpose of the present study was to determine whether hindlimb unloading of
rats alters vasoconstrictor and myogenic responsiveness of skeletal muscle
arterioles. After either 2 wk of hindlimb unloading (HU) or cage control (C),
second-order arterioles were isolated from the white portion of gastrocnemius
(WG; C: n = 9, HU: n = 10) or soleus (Sol; C: n = 9, HU: n = 10) muscles and
cannulated with two micropipettes connected to reservoir systems for in vitro
study. Intraluminal pressure was set at 60 cmH2O. The arterioles were exposed to
step changes in intraluminal pressure ranging from 20 to 140 cmH2O to determine
myogenic responsiveness and to KCl (10-100 mM) and norepinephrine (10(-9)-10(-4)
M) to determine vasoconstrictor responsiveness. Although maximal diameter of WG
arterioles was not different between C (185 +/- 12 microm) and HU (191 +/- 14
microm) rats, WG arterioles from HU rats developed less spontaneous tone (C: 33
+/- 5%, HU 20 +/-3%), were unable to maintain myogenic tone at pressures from 140
to 100 cmH2O, and were less sensitive to the vasoconstrictor effects of KCl and
norepinephrine (as indicated by a higher agonist concentration that produced 50%
of maximal vasoconstrictor response). In contrast, maximal diameter of Sol
arterioles from HU rats (117 +/- 12 microm) was smaller than that in C rats (148
+/- 14 microm). However, the development of spontaneous tone (C: 30 +/- 4%, HU:
36 +/- 5%), myogenic activity, and the responsiveness to vasoconstrictor agonists
were not different between Sol arterioles from C and HU rats. These results
indicate that hindlimb unloading diminishes the myogenic autoregulatory and
contractile responsiveness of arterioles from muscle composed of type IIB fibers
and suggest that the compromised ability to elevate vascular resistance after
exposure to microgravity may be related to these vascular alterations. In
addition, hindlimb unloading appears to induce vascular remodeling of arterioles
from muscle composed of type I fibers, as indicated by the decrease in maximal
diameter of arterioles from Sol muscle.
PMID- 10194201
TI - Role of nitric oxide in the vascular effects of local warming of the skin in
humans.
AB - Local warming of skin induces vasodilation by unknown mechanisms. To test whether
nitric oxide (NO) is involved, we examined effects of NO synthase (NOS)
inhibition with NG-nitro-L-arginine methyl ester (L-NAME) on vasodilation induced
by local warming of skin in six subjects. Two adjacent sites on the forearm were
instrumented with intradermal microdialysis probes for delivery of L-NAME and
sodium nitroprusside. Skin blood flow was monitored by laser-Doppler flowmetry
(LDF) at microdialysis sites. Local temperature (Tloc) of the skin at both sites
was controlled with special LDF probe holders. Mean arterial pressure (MAP;
Finapres) was measured and cutaneous vascular conductance calculated (CVC =
LDF/MAP = mV/mmHg). Data collection began with a control period (Tloc at both
sites = 34 degrees C). One site was then warmed to 41 degrees C while the second
was maintained at 34 degrees C. Local warming increased CVC from 1.44 +/- 0.41 to
4.28 +/- 0.60 mV/mmHg (P < 0.05). Subsequent L-NAME administration reduced CVC to
2.28 +/- 0.47 mV/mmHg (P < 0.05 vs. heating), despite the continued elevation of
Tloc. At a Tloc of 34 degrees C, L-NAME reduced CVC from 1.17 +/- 0.23 to 0.75 +/
0.11 mV/mmHg (P < 0.05). Administration of sodium nitroprusside increased CVC to
levels no different from those induced by local warming. Thus NOS inhibition
attenuated, and sodium nitroprusside restored, the cutaneous vasodilation induced
by elevation of Tloc; therefore, the mechanism of cutaneous vasodilation by local
warming requires NOS generation of NO.
PMID- 10194202
TI - Alpha-lipoic acid supplementation: tissue glutathione homeostasis at rest and
after exercise.
AB - Antioxidant nutrients have demonstrated potential in protecting against exercise
induced oxidative stress. alpha-Lipoic acid (LA) is a proglutathione dietary
supplement that is known to strengthen the antioxidant network. We studied the
effect of intragastric LA supplementation (150 mg/kg, 8 wk) on tissue LA levels,
glutathione metabolism, and lipid peroxidation in rats at rest and after
exhaustive treadmill exercise. LA supplementation increased the level of free LA
in the red gastrocnemius muscle and increased total glutathione levels in the
liver and blood. The exercise-induced decrease in heart glutathione S-transferase
activity was prevented by LA supplementation. Exhaustive exercise significantly
increased thiobarbituric acid-reactive substance levels in the liver and red
gastrocnemius muscle. LA supplementation protected against oxidative lipid damage
in the heart, liver, and red gastrocnemius muscle. This study reports that orally
supplemented LA is able to favorably influence tissue antioxidant defenses and
counteract lipid peroxidation at rest and in response to exercise.
PMID- 10194203
TI - Effect of a single bout of acute exercise on plasma human immunodeficiency virus
RNA levels.
AB - Acute exercise is known to activate the immune system and thus could lead to
increased human immunodeficiency virus (HIV) replication. We sought to determine
whether a single acute bout of exercise, similar to what people experience when
starting an intensive exercise program, has a detrimental effect on plasma HIV
RNA levels. Twenty-five patients with HIV infection performed one 15-min bout of
acute exercise. Absolute neutrophil counts, serum creatine phosphokinase, and 72
h urinary 3-methylhistidine (a marker of muscle protein breakdown) were measured
before and after the exercise, along with plasma HIV RNA levels. There were
increases in neutrophil counts (P < 0.06), serum creatine phosphokinase (P < 0.
01), and urinary 3-methylhistidine (P < 0.01) in response to exercise, indicating
a mild acute-phase response with muscle proteolysis. However, mean HIV RNA, which
was elevated at baseline in 22 of the 25 subjects (mean of 4 x 10(5) +/- 0.7 x
10(5) copies/ml), did not increase during the week after exercise (P = 0. 12).
Small changes in RNA were seen in the three subjects with initially undetectable
HIV RNA, but the significance of these changes is unclear. Acute exercise does
not have a deleterious effect on HIV replication in adults with high viral loads.
Because regular exercise training has not been shown to activate the acute-phase
response, the lack of increased viral loads in response to an acute exercise
intervention suggests that exercise training is safe in people with HIV
infection.
PMID- 10194204
TI - Hyperosmolar saline induces reflex nasal secretions, evincing neural
hyperresponsiveness in allergic rhinitis.
AB - We investigated whether hyperosmolar saline (HS), applied via paper disk onto the
septum of one nostril, induces a nasal secretory response. Furthermore, we
examined whether this response is accentuated in patients with active allergic
rhinitis (AR) compared with healthy volunteers. Unilateral HS produced
significant nasal secretions both ipsilateral and contralateral to the site of
challenge in the AR group and only ipsilaterally in the healthy group. The HS
induced nasal secretions were significantly greater in the AR vs. the healthy
subjects. In a separate study, we ascertained that the nasal response to HS is
neurally mediated and found that ipsilateral nerve blockade with lidocaine
significantly attenuates the HS-induced secretions bilaterally. In another group
of AR subjects, we determined whether nociceptive fibers were involved in this
response and found that sensory nerve desensitization with repeated application
of capsaicin attenuated the HS-induced nasal secretions. Finally, we determined
whether the secretory hyperresponsiveness in AR is attributable to increased
reactivity of submucosal glands rather than of nerves. We found that the dose
response to methacholine, which directly stimulates the glands, was identical
among AR and healthy subjects. We conclude that, in AR, nasal challenge with HS
induces significantly greater reflex secretions involving capsaicin-sensitive
nerve fibers, consistent with the notion of neural hyperresponsiveness in this
disease.
PMID- 10194205
TI - Increased brain capillaries in chronic hypoxia.
AB - The effect of chronic hypobaric hypoxia (28 days, 455 Torr) on the organization
of brain vessels was studied in Balb/c mice. In comparison to age-matched
controls kept at sea level, emulsion-perfused capillaries in hypoxic mice showed
marked dilation in all brain areas studied. Capillary length per unit volume of
tissue (Lv) was increased in the cerebellar granular layer, the caudate nucleus,
the globus pallidus, the substantia nigra, the superior colliculus, and the
dentate gyrus. There was a selective increase of Lv in the hippocampus (CA1
strata pyramidale and lacunosum and CA3 strata pyramidale and oriens) and in
somatosensory cortex layers V and VI, motor cortex layers II, III, V, and VI, and
auditory cortex layers II and III. An increase in capillary surface area per unit
volume of tissue was also determined in several brain areas, including layer IV
of somatosensory cortex, where Lv was not significantly increased. The O2
diffusion conductance and PO2 in the tissues were estimated with a mathematical
model. The remodeling of capillary diameter and length during chronic hypoxia
accounts for the significant increase of O2 conductance to neural tissues. Also
the estimated tissue PO2 in chronic brain hypoxia is markedly increased in the
caudate nucleus and the substantia nigra compared with acute hypoxia. These
results suggest that formation of new capillaries is an important mechanism to
restore the O2 deficit in chronic brain hypoxia and that local rates of energy
utilization may influence angiogenesis in different areas of the brain.
PMID- 10194206
TI - Stimulation of myofibrillar synthesis by exercise is mediated by more efficient
translation of mRNA.
AB - Resistance exercises stimulate protein synthesis in human muscle, but the roles
of changes in mRNA concentrations and changes in the efficiency of mRNA
translation have not been defined. The present study was done to determine
whether resistance exercise affects concentrations of total RNA, total mRNA,
actin mRNA, or myosin heavy-chain mRNA (total and isoform specific). Eight
subjects, 62-75 yr old, performed unilateral knee extensions at 80% of their one
repetition-maximum capacity on days 1, 3, and 6 of the study. On day 7, biopsies
of exercised and nonexercised vastus lateralis muscles were obtained.
Myofibrillar synthesis was determined by stable- isotope incorporation, and mRNA
concentrations were determined by membrane hybridization and PCR-based methods.
The exercise stimulated myofibrillar synthesis [30 +/- 6 (SE)%] without affecting
RNA or mRNA concentrations. The effect of exercise on protein synthesis in
individual subjects did not correlate with the effect on total RNA and mRNA
concentrations. These data suggest that the stimulation of myofibrillar synthesis
by resistance exercise is mediated by more efficient translation of mRNA.
PMID- 10194207
TI - Larynx vs. esophagus as reflexogenic sites for acid-induced bronchoconstriction
in dogs.
AB - Bronchoconstriction in asthmatic patients is frequently associated with
gastroesophageal reflux. However, it is still unclear whether bronchoconstriction
originates from the esophagus or from aspiration of the refluxate into the larynx
and larger airway. We compared the effect of repeated esophageal and laryngeal
instillations of HCl-pepsin (pH 1.0) on tracheal smooth muscle activity in eight
anesthetized and artificially ventilated dogs. Saline was used as control. We
used pressure in the cuff of an endotracheal tube (Pcuff) as a direct index of
smooth muscle activity at the level of the larger airways controlled by vagal
efferents. The Pcuff values of the first 60 s after instillations were averaged,
and the difference from the baseline values was evaluated. Changes in Pcuff were
significantly greater with laryngeal than with esophageal instillations (P =
0.0166). HCl-pepsin instillation into the larynx evoked greater responses than
did saline (P = 0.00543), whereas no differences were detected with esophageal
instillations. Repeated laryngeal exposure enhanced the responsiveness
significantly (P < 0. 001). Our data indicate that the larynx is more important
than the esophagus as a reflexogenic site for the elicitation of reflex
bronchoconstriction in response to acidic solutions.
PMID- 10194208
TI - Vagal esophageal receptors in anesthetized dogs: mechanical and chemical
responsiveness.
AB - This study was performed to evaluate the characteristics of esophageal receptors
in anesthetized and artificially ventilated dogs. The electrical activity of the
esophageal afferents was recorded from the peripheral cut end of the cervical
vagus nerve. A cuffed catheter was inserted into the esophagus at the level of
the third tracheal ring and was used to establish the esophageal location of the
endings. Most of the receptors were localized in the intrathoracic portion of the
esophagus. The majority of the receptors studied (36 of 43) showed a slow
adaptation to a maintained stretch of the esophageal wall. Vagal cooling blocked
receptor activity at temperatures ranging from 3.5 to 25 degrees C. Twenty-eight
of 43 receptors, including 4 rapidly adapting endings (RAR), were challenged with
saline, HCl + pepsin (HCl-P; pH 1) and distilled water (8 ml, 37 degrees C). HCl
P solutions specifically stimulated only three receptors; saline or water did
not. Five slowly adapting receptors and two RARs were also challenged with
topically applied capsaicin; only one RAR was stimulated. To ascertain a possible
effect of smooth muscle contraction, 17 receptors were tested with intravenous
injections of ACh and/or asphyxia; only 4 were stimulated. These characteristics
do not support an important reflexogenic role of the esophagus in response to
chemical stimuli.
PMID- 10194209
TI - Mechanisms of acute cardiovascular response to periodic apneas in sedated pigs.
AB - This study was designed to evaluate the importance of sympathoadrenal activation
in the acute cardiovascular response to apneas and the role of hypoxemia in this
response. In addition, we evaluated the contribution of the vagus nerve to apnea
responses after chemical sympathectomy. In six pigs preinstrumented with an
electromagnetic flow probe and five nonpreinstrumented pigs, effects of periodic
nonobstructive apneas were tested under the following six conditions: room air
breathing, 100% O2 supplementation, both repeated after administration of
hexamethonium (Hex), and both repeated again after bilateral vagotomy in addition
to Hex. With room air apneas, during the apnea cycle, there were increases in
mean arterial pressure (MAP; from baseline of 108 +/- 4 to 124 +/- 6 Torr, P <
0.01), plasma norepinephrine (from 681 +/- 99 to 1,825 +/- 578 pg/ml, P < 0.05),
and epinephrine (from 191 +/- 67 to 1,245 +/- 685 pg/ml, P < 0.05) but decreases
in cardiac output (CO; from 3.3 +/- 0.6 to 2.4 +/- 0.3 l/min, P < 0.01) and
cervical sympathetic nerve activity. With O2 supplementation relative to
baseline, apneas were associated with small increases in MAP (from 112 +/- 4 to
118 +/- 3 Torr, P < 0.01) and norepinephrine (from 675 +/- 97 to 861 +/- 170
pg/ml, P < 0.05). After Hex, apneas with room air were associated with small
increases in MAP (from 103 +/- 6 to 109 +/- 6 Torr, P < 0.05) and epinephrine
(from 136 +/- 45 to 666 +/- 467 pg/ml, P < 0.05) and decreases in CO (from 3.6 +/
0.4 to 3.2 +/- 0. 5 l/min, P < 0.05). After Hex, apneas with O2 supplementation
were associated with decreased MAP (from 107 +/- 5 to 100 +/- 5 Torr, P < 0.05)
and no other changes. After vagotomy + Hex, with room air and O2 supplementation,
apneas were associated with decreased MAP (from 98 +/- 6 to 76 +/- 7 and from 103
+/- 7 to 95 +/- 6 Torr, respectively, both P < 0.01) but increased CO [from 2.7
+/- 0.3 to 3. 2 +/- 0.4 l/min (P < 0.05) and from 2.4 +/- 0.2 to 2.7 +/- 0.2
l/min (P < 0.01), respectively]. We conclude that sympathoadrenal activation is
the major pressor mechanism during apneas. Cervical sympathetic nerve activity
does not reflect overall sympathoadrenal activity during apneas. Hypoxemia is an
important but not the sole trigger factor for sympathoadrenal activation. There
is an important vagally mediated reflex that contributes to the pressor response
to apneas.
PMID- 10194210
TI - High aerobic capacities in the skeletal muscles of pinnipeds: adaptations to
diving hypoxia.
AB - The objective was to assess the aerobic capacity of skeletal muscles in
pinnipeds. Samples of swimming and nonswimming muscles were collected from
Steller sea lions (Eumetopias jubatus, n = 27), Northern fur seals (Callorhinus
ursinus, n = 5), and harbor seals (Phoca vitulina, n = 37) by using a needle
biopsy technique. Samples were either immediately fixed in 2% glutaraldehyde or
frozen in liquid nitrogen. The volume density of mitochondria, myoglobin
concentration, citrate synthase activity, and beta-hydroxyacyl-CoA dehydrogenase
was determined for all samples. The swimming muscles of seals had an average
total mitochondrial volume density per volume of fiber of 9.7%. The swimming
muscles of sea lions and fur seals had average mitochondrial volume densities of
6.2 and 8.8%, respectively. These values were 1.7- to 2.0-fold greater than in
the nonswimming muscles. Myoglobin concentration, citrate synthase activity, and
beta-hydroxyacyl-CoA dehydrogenase were 1.1- to 2. 3-fold greater in the swimming
vs. nonswimming muscles. The swimming muscles of pinnipeds appear to be adapted
for aerobic lipid metabolism under the hypoxic conditions that occur during
diving.
PMID- 10194211
TI - Effect of chronic sodium cyanate administration on O2 transport and uptake in
hypoxic and normoxic exercise.
AB - Systemic O2 transport during maximal exercise at different inspired PO2 (PIO2)
values was studied in sodium cyanate-treated (CY) and nontreated (NT) rats. CY
rats exhibited increased O2 affinity of Hb (exercise O2 half-saturation pressure
of Hb = 27.5 vs. 42.5 Torr), elevated blood Hb concentration, pulmonary
hypertension, blunted hypoxic pulmonary vasoconstriction, and normal ventilatory
response to exercise. Maximal rate of convective O2 transport was higher and
tissue O2 extraction was lower in CY than in NT rats. The relative magnitude of
these opposing changes, which determined the net effect of cyanate on maximal O2
uptake (VO2 max), varied at different PIO2: VO2 max (ml. min-1. kg-1) was lower
in normoxia (72.8 +/- 1.9 vs. 81. 1 +/- 1.2), the same at 70 Torr PIO2 (55.4 +/-
1.4 vs. 54.1 +/- 1.4), and higher at 55 Torr PIO2 (48 +/- 0.7 vs. 40.4 +/- 1.9)
in CY than in NT rats. The beneficial effect of cyanate on VO2 max at 55 Torr
PIO2 disappeared when Hb concentration was lowered to normal. It is concluded
that the effect of cyanate on VO2 max depends on the relative changes in blood O2
convection and tissue O2 extraction, which vary at different PIO2. Although
uptake of O2 by the blood in the lungs is enhanced by cyanate, its release at the
tissues is limited, probably because of a reduction in the capillary-to-tissue
PO2 diffusion gradient secondary to the increased O2 affinity of Hb.
PMID- 10194212
TI - Enhanced peripheral chemoreflex function in conscious rabbits with pacing-induced
heart failure.
AB - The present study aimed to determine whether peripheral and/or central
chemoreflex function is altered in chronic heart failure (CHF) and whether
altered chemoreflex function contributes to sympathetic activation in CHF. A
rabbit model of pacing-induced CHF was employed. The development of CHF (3-4 wk
of pacing) was characterized by an enlarged heart, an attenuated contractility,
and an elevated central venous pressure. Renal sympathetic nerve activity (RSNA)
and minute volume (MV) of ventilation in response to stimulation of peripheral
chemoreceptors by isocapnic/hypoxic gases were measured in the conscious state.
It was found that the baseline RSNA at normoxia was higher in CHF rabbits than in
sham rabbits (35. 00 +/- 4.03 vs. 20.75 +/- 2.87% of maximum, P < 0.05).
Moreover, the magnitudes of changes in RSNA and MV in response to stimulation of
the peripheral chemoreceptors and the slopes of RSNA-arterial PO2 and MV-arterial
PO2 curves were greater in CHF than in sham rabbits. Inhibition of the peripheral
chemoreceptors by inhalation of 100% O2 decreased RSNA in CHF but not in sham
rabbits. The central chemoreflex function, as evaluated by the responses of RSNA
and MV to hyperoxic/hypercapnic gases, was not different between sham and CHF
rabbits. These data suggest that an enhancement of the peripheral chemoreflex
occurs in the rabbit model of pacing-induced CHF and that the enhanced peripheral
chemoreflex function contributes to the sympathetic activation in the CHF state.
PMID- 10194213
TI - Enhanced activity of carotid body chemoreceptors in rabbits with heart failure:
role of nitric oxide.
AB - An enhanced peripheral chemoreflex has been documented in patients with chronic
heart failure (CHF). This study aimed to examine the characteristics of carotid
body (CB) chemoreceptors in response to isocapnic hypoxia in a rabbit model of
pacing-induced CHF and to evaluate the possible role that nitric oxide (NO) plays
in the altered characteristics. The chemosensitive characteristics of the CB were
evaluated by recording single-unit activity from the carotid sinus nerve in both
an intact and a vascularly isolated preparation. It was found that the baseline
discharge under normoxia (intact preparation: arterial PO2 90-95 Torr; isolated
preparation: PO2 100-110 Torr) and the chemosensitivity in response to graded
hypoxia (PO2 40-70 Torr) were enhanced in CHF vs. sham rabbits. These alterations
were independent of the CB preparations (intact vs. isolated). NO synthase
inhibition by Nomega-nitro-L-arginine increased the baseline discharge and the
chemosensitivity in the intact preparation, whereas L-arginine (10(-5) M)
inhibited the baseline discharge and the chemosensitivity in the isolated
preparation in sham but not in CHF rabbits. S-nitroso-N-acetylpenicillamine, an
NO donor, inhibited the baseline discharge and the chemosensitivity in both CB
preparations in CHF rabbits but only in the isolated preparation in sham rabbits.
The amount of NO produced in vitro by the CB under normoxia was less in CHF
rabbits than in sham rabbits (P < 0.05). NO synthase-positive varicosities of
nerve fibers within the CB were less in CHF rabbits than in sham rabbits (P <
0.05). These data indicate that an enhanced input from CB occurs in the rabbit
model of pacing-induced CHF and that an impairment of NO production may
contribute to this alteration.
PMID- 10194214
TI - Altered reflex sensitivity after repeated and prolonged passive muscle
stretching.
AB - Experiments were carried out to test the effect of prolonged and repeated passive
stretching (RPS) of the triceps surae muscle on reflex sensitivity. The results
demonstrated a clear deterioration of muscle function immediately after RPS.
Maximal voluntary contraction, average electromyographic activity of the
gastrocnemius and soleus muscles, and zero crossing rate of the soleus muscle
(recorded from 50% maximal voluntary contraction) decreased on average by 23.2,
19.9, 16.5, and 12.2%, respectively. These changes were associated with a clear
immediate reduction in the reflex sensitivity; stretch reflex peak-to-peak
amplitude decreased by 84. 8%, and the ratio of the electrically induced maximal
Hoffmann reflex to the maximal mass compound action potential decreased by 43.
8%. Interestingly, a significant (P < 0.01) reduction in the stretch-resisting
force of the measured muscles was observed. Serum creatine kinase activity stayed
unaltered. This study presents evidence that the mechanism that decreases the
sensitivity of short-latency reflexes can be activated because of RPS. The origin
of this system seems to be a reduction in the activity of the large-diameter
afferents, resulting from the reduced sensitivity of the muscle spindles to
repeated stretch.
PMID- 10194215
TI - Reduced reflex sensitivity persists several days after long-lasting stretch
shortening cycle exercise.
AB - The mechanisms related to the acute and delayed secondary impairment of the
stretch reflex function were investigated after long-lasting stretch-shortening
cycle exercise. The results demonstrated a clear deterioration in muscle function
immediately after fatigue, which was accompanied by a clear reduction in active
and passive reflex sensitivity. For active and passive stretch reflexes, this
reduction was biphasic (P < 0.05 to P < 0.001). However, for the ratio of the
electrically induced maximal Hoffmann reflex to the maximal mass compound action
potential, only one significant reduction was seen immediately after fatigue
(71.2%, P < 0.01). A similar significant (P < 0.01) decrease in the stretch
resisting force of the muscle was also detected. Clear increases were found in
the indirect markers of muscle damage (serum creatine kinese activity and
skeletal troponin I), which could imply the occurrence of ultrastructural muscle
damage. It is suggested that the acute reduction in reflex sensitivity is of
reflex origin and due to two active mechanisms, disfacilitation and presynaptic
inhibition. However, the delayed second decline in the sensitivity of some reflex
parameters may be attributable to the secondary injury, because of some
inflammatory response to the muscle damage. This might emphasize the role of
presynaptic inhibition via group III and IV muscle afferents.
PMID- 10194216
TI - Compensatory alveolar growth normalizes gas-exchange function in immature dogs
after pneumonectomy.
AB - To determine the extent and sources of adaptive response in gas-exchange to major
lung resection during somatic maturation, immature male foxhounds underwent right
pneumonectomy (R-Pnx, n = 5) or right thoracotomy without pneumonectomy (Sham, n
= 6) at 2 mo of age. One year after surgery, exercise capacity and pulmonary gas
exchange were determined during treadmill exercise. Lung diffusing capacity (DL)
and cardiac output were measured by a rebreathing technique. In animals after R
Pnx, maximal O2 uptake, lung volume, arterial blood gases, and DL during exercise
were completely normal. Postmortem morphometric analysis 18 mo after R-Pnx (n =
3) showed a vigorous compensatory increase in alveolar septal tissue volume
involving all cellular compartments of the septum compared with the control lung;
as a result, alveolar-capillary surface areas and DL estimated by morphometry
were restored to normal. In both groups, estimates of DL by the morphometric
method agreed closely with estimates obtained by the physiological method during
peak exercise. These data show that extensive lung resection in immature dogs
stimulates a vigorous compensatory growth of alveolar tissue in excess of
maturational lung growth, resulting in complete normalization of aerobic capacity
and gas-exchange function at maturity.
PMID- 10194217
TI - Gas supersaturation in the cecal wall of mice due to bacterial CO2 production.
AB - PCO2 in the lumen and serosa of cecum and jejunum was measured in mice. The
anesthetic used was a fentanyl-fluanisone-midazolam mixture. PCO2 was recorded in
vivo and postmortem. PCO2 was 409 +/- 32 Torr (55 +/- 4 kPa) in the cecal lumen
and 199 +/- 22 Torr (27 +/- 3 kPa) on the serosa in normal mice. Irrigation of
the cecum resulted in serosal and luminal PCO2 levels of 65-75 Torr. Cecal PCO2
was significantly lower in germ-free mice (65 +/- 5 Torr). Cecal PCO2 increased
significantly after introduction of normal bacterial flora into germ-free mice.
Introduction of bacterial monocultures into germ-free mice had no effect. After
the deaths of the mice, cecal PCO2 increased rapidly in normal mice. The
intestinal bacteria produced the majority of the cecal PCO2, and the use of
tonometry in intestinal segments with a high bacterial activity should be
interpreted with caution. We propose that serosal PCO2 levels >150-190 Torr (20
25 kPa) in the cecum of mice with a normal circulation may represent a state of
gas supersaturation in the cecal wall.
PMID- 10194219
TI - Expiratory time determined by individual anxiety levels in humans.
AB - We have previously found that individual anxiety levels influence respiratory
rates in physical load and mental stress (Y. Masaoka and I. Homma. Int. J.
Psychophysiol. 27: 153-159, 1997). On the basis of that study, in the present
study we investigated the metabolic outputs during tests and analyzed the
respiratory timing relationship between inspiration and expiration, taking into
account individual anxiety levels. Disregarding anxiety levels, there were
correlations between O2 consumption (VO2) and minute ventilation (VE) and between
VO2 and tidal volume in the physical load test, but no correlations were observed
in the noxious audio stimulation test. There was a volume-based increase in
respiratory patterns in physical load; however, VE increased not only for the
adjustment of metabolic needs but also for individual mental factors; anxiety
participated in this increase. In the high-anxiety group, the VE-to-VO2 ratio,
indicating ventilatory efficiency, increased in both tests. In the high-anxiety
group, increases in respiratory rate contributed to a VE increase, and there were
negative correlations between expiratory time and anxiety scores in both tests.
In an awake state, the higher neural structure may dominantly affect the
mechanism of respiratory rhythm generation. We focus on the relationship between
expiratory time and anxiety and show diagrams of respiratory output, allowing for
individual personality.
PMID- 10194218
TI - Physiological responses of exercised-fatigued individuals exposed to wet-cold
conditions.
AB - Thirteen healthy and fit men [age = 27 +/- 8 (SD) yr, height = 177 +/- 5 cm, mass
= 75 +/- 7 kg, body fat = 14 +/- 5%, maximal O2 consumption = 51 +/- 4 ml. kg-1.
min-1] participated in an experiment designed to test their thermoregulatory
response to a challenging cold exposure after 5 h of demanding mixed exercise
during which only water was consumed. Subjects expended 7,314 +/- 741 kJ on
cycling, rowing, and treadmill-walking machines, performed 8,403 +/- 1,401 kg. m
of mechanical work during resistance exercises, and completed 120 inclined sit
ups. Subjects then assumed a seated position in a 10 degrees C air environment
while wearing shorts, T-shirt, rain hat, and neoprene gloves and boots. After 30
min the subjects were showered continuously with cold water ( approximately 920
ml/min at 10 degrees C) on their backs accompanied by a 6 km/h wind for up to 4
h. Blood samples were taken from the nondominant arm every 30 min during the
exposure and assayed for energy metabolites, hormones, indexes of hydration, and
neurotransmitters. Counterbalanced control trials without prior exercise were
also conducted. Blood insulin was higher during the control trial, whereas values
of glycerol, nonesterified fatty acids, beta-hydroxybutyrate, lactate, cortisol,
free triiodothyronine, and thyroxine were lower. Three subjects lasted the
maximum duration of 4.5 h for control and fatigue trials, with final rectal
temperatures of 36.43 +/- 0.21 and 36.08 +/- 0.49 degrees C, respectively.
Overall, the duration of 172 +/- 68 (SD) min for the fatigue trial was not
significantly different from that of the control trial (197 +/- 72 min) and,
therefore, was not affected by the preexposure exercise. Although duration was
positively correlated to body fatness and shivering intensity, the latter was not
correlated to any physical characteristic or the fitness level of the individual.
PMID- 10194220
TI - Effects of activation frequency and force on low-frequency fatigue in human
skeletal muscle.
AB - No comparison of the amount of low-frequency fatigue (LFF) produced by different
activation frequencies exists, although frequencies ranging from 10 to 100 Hz
have been used to induce LFF. The quadriceps femoris of 11 healthy subjects were
tested in 5 separate sessions. In each session, the force-generating ability of
the muscle was tested before and after fatigue and at 2, approximately 13, and
approximately 38 min of recovery. Brief (6-pulse), constant-frequency trains of
9.1, 14.3, 33.3, and 100 Hz and a 6-pulse, variable-frequency train with a mean
frequency of 14.3 Hz were delivered at 1 train/s to induce fatigue. Immediately
postfatigue, there was a significant effect of fatiguing protocol frequency.
Muscles exhibited greater LFF after stimulation with the 9.1-, 14.3-, and
variable-frequency trains. These three trains also produced the greatest mean
force-time integrals during the fatigue test. At 2, approximately 13, and
approximately 38 min of recovery, however, the LFF produced was independent of
the fatiguing protocol frequency. The findings are consistent with theories
suggesting two independent mechanisms behind LFF and may help identify the
optimal activation pattern when functional electrical stimulation is used.
PMID- 10194221
TI - Tomographical description of tennis-loaded radius: reciprocal relation between
bone size and volumetric BMD.
AB - Effects of long-term tennis loading on volumetric bone mineral density (vBMD) and
geometric properties of playing-arm radius were examined. Paired forearms of 16
tennis players (10 women) and 12 healthy controls (7 women), aged 18-24 yr, were
scanned at mid and distal site by using peripheral quantitative computerized
tomography. Tomographic data at midradius showed that tennis playing led to a
slight decrease in cortical vBMD (-0.8% vs. nonplaying arm, P < 0. 05) and
increase both in periosteal and endocoritcal bone area (+15. 2% for periosteal
bone, P < 0.001; and +18.8% for endocortical bone, P < 0.001). These data suggest
that, together with an increase in cortical thickness (+6.4%, P < 0.01), cortical
drift toward periosteal direction resulted in improvement of mechanical
characteristics of the playing-arm midradius. Enlargement of periosteal bone area
was also observed at distal radius (+6.8%, P < 0.01), and the relative side-to
side difference in periosteal bone area was inversely related to that in
trabecular vBMD (r = -0.53, P < 0.05). We conclude that an improvement of
mechanical properties of young adult bone in response to long-term exercise is
related to geometric adaptation but less to changes in vBMD.
PMID- 10194222
TI - Eosinophils in the bronchial mucosa in relation to methacholine dose-response
curves in atopic asthma.
AB - Asthma is characterized by both local infiltration of eosinophils in the
bronchial mucosa and bronchial hyperreactivity (BHR). A detailed characterization
of BHR implies analysis of a histamine or methacholine dose-response curve
yielding not only the dose at 20% fall of baseline forced expiratory volume in 1
s (FEV1), but also a plateau (P) representing the maximal narrowing response in
terms of percent change in FEV1 and reactivity as the steepest slope at 50% of P
(%FEV1/doubling dose). In the baseline condition, the specific airway conductance
(sGaw) may be considered closely related to airway lumen diameter. In 20
nonsmoking asthmatic patients, methacholine dose-response curves were obtained,
and a sigmoid model fit yielded the BHR indexes. Immunohistochemistry with the
monoclonal antibodies (EG1 and EG2) was used to recognize the total number of
eosinophils and activated eosinophils, respectively. The number of activated
eosinophils was significantly correlated to both P (r = 0.62; P < 0.05) and sGaw
(r = -0.52; P < 0.05), whereas weaker and nonsignificant correlations were found
for dose at 20% fall of baseline FEV1 and the total number of eosinophils. We
conclude that the number of activated eosinophils can be considered a marker of
the inflammation-induced decrease of airway lumen diameter as represented by the
plateau index and sGaw.
PMID- 10194223
TI - Role of expiratory flow limitation in determining lung volumes and ventilation
during exercise.
AB - We determined the role of expiratory flow limitation (EFL) on the ventilatory
response to heavy exercise in six trained male cyclists [maximal O2 uptake = 65
+/- 8 (range 55-74) ml. kg-1. min-1] with normal lung function. Each subject
completed four progressive cycle ergometer tests to exhaustion in random order:
two trials while breathing N2O2 (26% O2-balance N2), one with and one without
added dead space, and two trials while breathing HeO2 (26% O2-balance He), one
with and one without added dead space. EFL was defined by the proximity of the
tidal to the maximal flow-volume loop. With N2O2 during heavy and maximal
exercise, 1) EFL was present in all six subjects during heavy [19 +/- 2% of tidal
volume (VT) intersected the maximal flow-volume loop] and maximal exercise (43 +/
8% of VT), 2) the slopes of the ventilation (DeltaVE) and peak esophageal
pressure responses to added dead space (e.g., DeltaVE/DeltaPETCO2, where PETCO2
is end-tidal PCO2) were reduced relative to submaximal exercise, 3) end
expiratory lung volume (EELV) increased and end-inspiratory lung volume reached a
plateau at 88-91% of total lung capacity, and 4) VT reached a plateau and then
fell as work rate increased. With HeO2 (compared with N2O2) breathing during
heavy and maximal exercise, 1) HeO2 increased maximal flow rates (from 20 to 38%)
throughout the range of vital capacity, which reduced EFL in all subjects during
tidal breathing, 2) the gains of the ventilatory and inspiratory esophageal
pressure responses to added dead space increased over those during room air
breathing and were similar at all exercise intensities, 3) EELV was lower and end
inspiratory lung volume remained near 90% of total lung capacity, and 4) VT was
increased relative to room air breathing. We conclude that EFL or even impending
EFL during heavy and maximal exercise and with added dead space in fit subjects
causes EELV to increase, reduces the VT, and constrains the increase in
respiratory motor output and ventilation.
PMID- 10194224
TI - Human muscle performance and PCr hydrolysis with varied inspired oxygen
fractions: a 31P-MRS study.
AB - The purpose of this study was to use 31P-magnetic resonance spectroscopy to
examine the relationships among muscle PCr hydrolysis, intracellular H+
concentration accumulation, and muscle performance during incremental exercise
during the inspiration of gas mixtures containing different fractions of inspired
O2 (FIO2). We hypothesized that lower FIO2 would result in a greater disruption
of intracellular homeostasis at submaximal workloads and thereby initiate an
earlier onset of fatigue. Six subjects performed plantar flexion exercise on
three separate occasions with the only variable altered for each exercise bout
being the FIO2 (either 0.1, 0.21, or 1.00 O2 in balance N2). Work rate was
increased (1-W increments starting at 0 W) every 2 min until exhaustion. Time to
exhaustion (and thereby workload achieved) was significantly (P < 0.05) greater
as FIO2 was increased. Muscle phosphocreatine (PCr) concentration, Pi
concentration, and pH at exhaustion were not significantly different among the
three FIO2 conditions. However, muscle PCr concentration and pH were
significantly reduced at identical submaximal workloads (and thereby equivalent
rates of respiration) above 4-5 W during the lowest FIO2 condition compared with
the other two FIO2 conditions. These results demonstrate that exhaustion during
all FIO2 occurred when a particular intracellular environment was achieved and
suggest that during the lowest FIO2 condition, the greater PCr hydrolysis and
intracellular acidosis at submaximal workloads may have contributed to the
significantly earlier time to exhaustion.
PMID- 10194225
TI - Effects of a high-fat diet and voluntary wheel running on gluconeogenesis and
lipolysis in rats.
AB - The purpose of the present study was to determine the effects of diet composition
and exercise on glycerol and glucose appearance rate (Ra) and on nonglycerol
gluconeogenesis (Gneo) in vivo. Male Wistar rats were fed a high-starch diet (St,
68% of energy as cornstarch, 12% corn oil) for a 2-wk baseline period and then
were randomly assigned to one of four experimental groups: St (n = 7), high-fat
(HF; 35% cornstarch, 45% corn oil; n = 8), St with free access to exercise wheels
(StEx; n = 7), and HF with free access to exercise wheels (HFEx; n = 7). After 8
wk, glucose Ra when using [3-3H]glucose, glycerol Ra when using [2H5]glycerol
(estimate of whole body lipolysis), and [3-13C]alanine incorporation into glucose
(estimate of alanine Gneo) were determined. Body weight and fat pad mass were
significantly (P < 0.05) decreased in exercise vs. sedentary animals only. The
average amount of exercise was not significantly different between StEx (3,212 +/
659 m/day) and HFEx (3,581 +/- 765 m/day). The ratio of glucose to alanine
enrichment and absolute glycerol Ra (micromol/min) were higher (P < 0.05) in HF
and HFEx compared with St and StEx rats. In separate experiments, the ratio of 3H
in C-2 to C-6 of glucose from 3H2O (estimate of Gneo from pyruvate) was also
higher (P < 0.05) in HF (n = 5) and HFEx (n = 5), compared with St (n = 5) and
StEx (n = 5) rats. Voluntary wheel running did not significantly increase
estimated alanine or pyruvate Gneo or absolute glycerol Ra. Voluntary wheel
running increased (P < 0.05) glycerol Ra when normalized to fat pad mass. These
data suggest that a high-fat diet can increase in vivo Gneo from precursors that
pass through pyruvate. They also suggest that changes in the absolute rate of
glycerol Ra may contribute to the high-fat diet-induced increase in Gneo.
PMID- 10194226
TI - Transport of colloidal particles in lymphatics and vasculature after subcutaneous
injection.
AB - This study was designed to determine the transport of subcutaneously injected
viral-size colloid particles into the lymph and the vascular system in the hind
leg of the dog. Transport of two colloid particles, with average size
approximately 1 and 0.41 microm, respectively, and with and without leg rotation,
was tested. Leg rotation serves to enhance the lymph flow rates. The right
femoral vein, lymph vessel, and left femoral artery were cannulated while the
animal was under anesthesia, and samples were collected at regular intervals
after subcutaneous injection of the particles at the right knee level. The number
of particles in the samples were counted under fluorescence microscopy by using a
hemocytometer. With and without leg rotation, both particle sets were rapidly
taken up into the venous blood and into the lymph fluid. The number of particles
carried away from the injection site within the first 5 min was <5% of the
injected pool. Particles were also seen in arterial blood samples; this suggests
reflow and a prolonged residence time in the blood. These results show that
particles the size of viruses are rapidly taken up into the lymphatics and blood
vessels after subcutaneous deposition.
PMID- 10194227
TI - Evaluation of pulmonary resistance and maximal expiratory flow measurements
during exercise in humans.
AB - To evaluate methods used to document changes in airway function during and after
exercise, we studied nine subjects with exercise-induced asthma and five subjects
without asthma. Airway function was assessed from measurements of pulmonary
resistance (RL) and forced expiratory vital capacity maneuvers. In the asthmatic
subjects, forced expiratory volume in 1 s (FEV1) fell 24 +/- 14% and RL increased
176 +/- 153% after exercise, whereas normal subjects experienced no change in
airway function (RL -3 +/- 8% and FEV1 -4 +/- 5%). During exercise, there was a
tendency for FEV1 to increase in the asthmatic subjects but not in the normal
subjects. RL, however, showed a slight increase during exercise in both groups.
Changes in lung volumes encountered during exercise were small and had no
consistent effect on RL. The small increases in RL during exercise could be
explained by the nonlinearity of the pressure-flow relationship and the increased
tidal breathing flows associated with exercise. In the asthmatic subjects, a deep
inspiration (DI) caused a small, significant, transient decrease in RL 15 min
after exercise. There was no change in RL in response to DI during exercise in
either asthmatic or nonasthmatic subjects. When percent changes in RL and FEV1
during and after exercise were compared, there was close agreement between the
two measurements of change in airway function. In the groups of normal and mildly
asthmatic subjects, we conclude that changes in lung volume and DIs had no
influence on RL during exercise. Increases in tidal breathing flows had only
minor influence on measurements of RL during exercise. Furthermore, changes in RL
and in FEV1 produce equivalent indexes of the variations in airway function
during and after exercise.
PMID- 10194228
TI - Effect of upper airway negative pressure on proprioceptive afferents from the
tongue.
AB - We examined whether receptors in the tongue muscle respond to negative upper
airway pressure (NUAP). In six cats, one hypoglossal nerve was cut and its distal
end was prepared for single-fiber recording. Twelve afferent fibers were selected
for study on the basis of their sensitivity to passive stretch (PS) of the
tongue. Fiber discharge frequency was measured during PS of the tongue and after
the rapid onset of constant NUAP. During PS of 1-3 cm, firing frequency increased
from 17 +/- 7 to 40 +/- 11 (SE) Hz (P < 0.01). In addition, 8 of the 12 fibers
responded to NUAP (-10 to -30 cmH2O), with firing frequency increasing from 23 +/
9 to 41 +/- 9 Hz (P < 0.001). In two fibers tested, the increase in firing
frequency in response to NUAP was not altered by topical anesthesia (10%
lignocaine) applied liberally to the entire upper airway mucosa. Our results
demonstrate that afferent discharges from the hypoglossal nerve are elicited by
1) stretching of the tongue and 2) NUAP before and after upper airway anesthesia.
We speculate that activation of proprioceptive mechanoreceptors in the cat's
tongue provides an additional pathway for the reflex activation of upper airway
dilator muscles in response to NUAP, independent of superficially located mucosal
mechanoreceptors.
PMID- 10194229
TI - Dispersion of 0.5- to 2-micron aerosol in microG and hypergravity as a probe of
convective inhomogeneity in the lung.
AB - We used aerosol boluses to study convective gas mixing in the lung of four
healthy subjects on the ground (1 G) and during short periods of microgravity
(microG) and hypergravity ( approximately 1. 6 G). Boluses of 0.5-, 1-, and 2
micron-diameter particles were inhaled at different points in an inspiration from
residual volume to 1 liter above functional residual capacity. The volume of air
inhaled after the bolus [the penetration volume (Vp)] ranged from 150 to 1,500
ml. Aerosol concentration and flow rate were continuously measured at the mouth.
The dispersion, deposition, and position of the bolus in the expired gas were
calculated from these data. For each particle size, both bolus dispersion and
deposition increased with Vp and were gravity dependent, with the largest
dispersion and deposition occurring for the largest G level. Whereas intrinsic
particle motions (diffusion, sedimentation, inertia) did not influence dispersion
at shallow depths, we found that sedimentation significantly affected dispersion
in the distal part of the lung (Vp >500 ml). For 0.5-micron-diameter particles
for which sedimentation velocity is low, the differences between dispersion in
microG and 1 G likely reflect the differences in gravitational convective
inhomogeneity of ventilation between microG and 1 G.
PMID- 10194230
TI - Increased cerebral extracellular adenosine and decreased PGE2 during ethanol
induced inhibition of FBM.
AB - Adenosine and PGE2 are neuromodulators, both of which inhibit fetal breathing
movements (FBM). Although circulating PGE2 has been implicated as a mediator of
ethanol-induced inhibition of FBM in the late-gestation ovine fetus, a role for
adenosine has not been examined. The objective of this study was to determine the
effect of maternal ethanol infusion on ovine fetal cerebral extracellular fluid
adenosine and PGE2 concentrations by using in utero microdialysis and to relate
any changes to ethanol-induced inhibition of FBM. Dialysate samples were obtained
from the fetal parietal cortex over 70 h after surgery to determine steady-state
extracellular fluid adenosine and PGE2 concentrations. On each of postoperative
days 3 and 4, after a 2-h baseline period, ewes received a 1-h infusion of
ethanol (1 g/kg maternal body wt) or an equivalent volume of saline, and the
fetus was monitored for a further 11 h with 30-min dialysate samples collected
throughout. Immediately after surgery, dialysate PGE2 and adenosine
concentrations were 3.7 +/- 0.7 and 296 +/- 127 nM, respectively. PGE2 did not
change over the 70 h, whereas adenosine decreased to 59 +/- 14 nM (P < 0.05) at 4
h and then remained unchanged. Ethanol decreased dialysate PGE2 concentration for
2 h (3.3 +/- 0.3 to 1.9 +/- 0.4 nM; P < 0.05) and increased adenosine
concentration for 6 h (87 +/- 13 to a maximum of 252 +/- 59 nM, P < 0.05).
Ethanol decreased FBM incidence from 47 +/- 7 to 16 +/- 5% (P < 0.01) for 8 h.
Saline infusion did not change dialysate adenosine or PGE2 concentrations or FBM
incidence. These data are consistent with the hypothesis that fetal cerebral
adenosine, and not PGE2, is the primary mediator of ethanol-induced inhibition of
FBM at 123 days of gestation in sheep.
PMID- 10194231
TI - Modeling the effects of proteins on pH in plasma.
AB - Stewart's model of plasma acid-base balance (Can. J. Physiol. Pharmacol. 61: 1444
1461, 1983) has three weaknesses in the treatment of weak acids: 1) the
combination of all weak acids into one entity, 2) inappropriate chemistry for the
protein combination with H+, and 3) undocumented values for the dissociation
parameters. The present study models serum albumin acid-base properties by fixed
negative charges and the association of H+ with the imidazole side chain of
histidine. This model has three parameters: 1) the net negative fixed charge (21
eq/mol), 2) the number of histidine residues (16/mol), and 3) the association
constant for the imidazole side chain (1.77 x 10(-7) eq/l), all determined from
published values. The model was compared with that of Figge, Mydosh, and Fencl
(J. Lab. Clin. Med. 120: 713-719, 1992) and with the pH data of Figge, Rossing,
and Fencl (J. Lab. Clin. Med. 117: 453-467, 1991). The predictions of pH were
excellent, comparable to those found by Figge, Mydosh, and Fencl. The model has
the advantages that its structure and parameter values are supported by the
literature and that the acid-base effects of factors modifying protein can be
investigated.
PMID- 10194232
TI - Relationship between activity levels, aerobic fitness, and body fat in 8- to 10
yr-old children.
AB - The relationships between children's activity, aerobic fitness, and fatness are
unclear. Indirect estimates of activity, e.g., heart rate (HR) and recall, may
mask any associations. The purpose of this study was to assess these
relationships by using the Tritrac-R3D, a pedometer, and heart rate. Thirty-four
children, ages 8-10 yr, participated in the study. The Tritrac and pedometer were
worn for up to 6 days. HR was measured for 1 day. Activity measured by Tritrac or
pedometer correlated positively to fitness in the whole group (Tritrac, r = 0.66;
pedometer, r = 0.59; P < 0.01) and in boys and girls separately (P < 0.05) and
correlated negatively to fatness in the whole group (r = -0.42, P < 0.05). In
contrast, HR did not correlate significantly to fitness, and HR of >139 beats/min
correlated positively to fatness in girls (r = 0.64, P < 0.05). This suggests
that HR is misleading as a measure of activity. This study supports a positive
relationship between activity and fitness and suggests a negative relationship
between fatness and activity.
PMID- 10194233
TI - Serum levels of total and free IGF-I and IGFBP-3 are increased and maintained in
long-term training.
AB - The goals of this study were to determine whether the long-term training regimens
experienced by competitive collegiate swimmers would result in altered levels of
total and free serum insulin-like growth factor I (IGF-I) as well as IGF-binding
proteins (BP) IGFBP-1 and -3. Two male (Teams 1M and 2M) and one female (Team 2F)
teams were studied at the start of training, after 2 mo of training, after 4 mo
(2-4 mo had the highest volume of training), after 5 mo (near the end of
tapering; only for Team 1M), and several days after training was over. For Team
1M, total IGF-I concentrations were increased by 76% after 4 mo and were
subsequently maintained at this level. Total IGF-I responses were more variable
for Teams 2F and 2M. Free IGF-I levels were increased nearly twofold for all
teams at 2 mo and were maintained or increased further with subsequent training.
Only the levels of free IGF-I for Team 1M returned to pretraining values after
training had ended. Training had little effect on IGFBP-1 levels. For all teams,
serum IGFBP-3 was elevated by 4 mo of training (for Team 2F it was increased at 2
mo) by 30-97% and remained at these higher levels thereafter. The ratio of total
IGF-I to IGFBP-3 was not increased by training in any group. These data indicate
that serum levels of total and free IGF-I and total IGFBP-3 can be increased with
intense training and maintained with reduced training (tapering). The findings
show that changes in free IGF-I levels are not accounted for by alterations in
the total IGF-I/IGFBP-3 complex or in IGFBP-3 levels and indicate that there are
other important determinants of free IGF-I.
PMID- 10194234
TI - A population-based study of survival and childbearing among female subjects with
birth defects and the risk of recurrence in their children.
AB - BACKGROUND AND METHODS: Persons with birth defects are at high risk for death
during the perinatal period and infancy. Less is known about the later survival
or reproduction of such persons. We studied a cohort that comprised 8192 women
and adolescent girls with registered birth defects and 451,241 women and
adolescent girls with no birth defects, all of whom were born in Norway from 1967
through 1982. The rate of survival was determined through 1992, and the rate of
childbearing was determined through October 1997. We also estimated the risk of
birth defects in the children of these subjects. RESULTS: Among the subjects with
birth defects, 80 percent survived to 15 years of age, as compared with 98
percent of those with no birth defects. Among the surviving subjects, 53 percent
of those with birth defects gave birth to at least one infant by the age of 30
years, as compared with 67 percent of those with no birth defects. The subjects
with birth defects were one third less likely to give birth by the age of 30 than
those with no birth defects. The children of the subjects with birth defects had
a significantly higher risk of birth defects than the children of those with no
birth defects (relative risk, 1.6; 95 percent confidence interval, 1.3 to 2.1).
This increased risk was confined entirely to the specific defect carried by the
mother, with the relative risk of recurrence varying from 5.5 to 82 according to
the defect. In contrast, there was no increase in the risk of having an infant
with a different type of defect. CONCLUSIONS: Women and girls with birth defects
have decreased survival as compared with those with no birth defects, especially
in the first years of life, and are less likely to have children. In addition,
they have an increased risk of having children with the same defect.
PMID- 10194236
TI - Recurrence of bronchioloalveolar carcinoma in transplanted lungs.
AB - BACKGROUND: Bronchioloalveolar carcinoma is a distinctive subtype of typical
adenocarcinoma of the lung that tends to metastasize widely throughout the lungs
but less commonly elsewhere. Because conventional therapies for intrapulmonary
metastatic bronchioloalveolar carcinoma are generally ineffective, we treated
seven patients who had intrapulmonary metastatic bronchioloalveolar carcinoma
with lung transplantation. METHODS: Seven patients with biopsy-proved
bronchioloalveolar carcinoma and no evidence of extrapulmonary disease received
transplants of either one or two cadaveric lungs. At transplantation, all native
lung tissue was removed and replaced with a donor lung or lungs. The patients
received the usual post-transplantation care given at the institution. RESULTS:
Four of the seven patients had recurrent bronchioloalveolar carcinoma within the
donor lungs; the recurrences appeared from 10 to 48 months after transplantation.
All recurrences were limited to the donor lungs. Histologic and molecular
analyses showed that the recurrent tumors in three patients originated from the
recipients of the transplants. CONCLUSIONS: Lung transplantation for
bronchioloalveolar carcinoma is technically feasible, but recurrence of the
original tumor within the donor lungs up to four years after transplantation was
common.
PMID- 10194235
TI - Oral ganciclovir for patients with cytomegalovirus retinitis treated with a
ganciclovir implant. Roche Ganciclovir Study Group.
AB - BACKGROUND: The intraocular ganciclovir implant is effective for local treatment
of cytomegalovirus retinitis in patients with the acquired immunodeficiency
syndrome (AIDS), but it does not treat or prevent other systemic manifestations
of cytomegalovirus infection. METHODS: Three hundred seventy-seven patients with
AIDS and unilateral cytomegalovirus retinitis were randomly assigned to one of
three treatments: a ganciclovir implant plus oral ganciclovir (4.5 g daily), a
ganciclovir implant plus oral placebo, or intravenous ganciclovir alone. The
primary outcome measure was the development of new cytomegalovirus disease,
either contralateral retinitis or biopsy-proved extraocular disease. RESULTS: The
incidence of new cytomegalovirus disease at six months was 44.3 percent in the
group assigned to the ganciclovir implant plus placebo, as compared with 24.3
percent in the group assigned to the ganciclovir implant plus oral ganciclovir
(P=0.002) and 19.6 percent in the group assigned to intravenous ganciclovir alone
(P<0.001). As compared with placebo, oral ganciclovir reduced the overall risk of
new cytomegalovirus disease by 37.6 percent over the one-year period of the study
(P=0.02). However, in the subgroup of 103 patients who took protease inhibitors,
the rates of new cytomegalovirus disease were low and of similar magnitude,
regardless of treatment assignment. Progression of retinitis in the eye that
initially received an implant was delayed by the addition of oral ganciclovir, as
compared with placebo (P=0.03). Treatment with oral or intravenous ganciclovir
reduced the risk of Kaposi's sarcoma by 75 percent (P=0.008) and 93 percent
(P<0.001), respectively, as compared with placebo. CONCLUSIONS: In patients with
AIDS and cytomegalovirus retinitis, oral ganciclovir in conjunction with a
ganciclovir implant reduces the incidence of new cytomegalovirus disease and
delays progression of the retinitis. Treatment with oral or intravenous
ganciclovir also reduces the risk of Kaposi's sarcoma.
PMID- 10194237
TI - Central hypothyroidism associated with retinoid X receptor-selective ligands.
AB - BACKGROUND: The occurrence of symptomatic central hypothyroidism (characterized
by low serum thyrotropin and thyroxine concentrations) in a patient with
cutaneous T-cell lymphoma during therapy with the retinoid X receptor-selective
ligand bexarotene led us to hypothesize that such ligands could reversibly
suppress thyrotropin production by a thyroid hormone-independent mechanism and
thus cause central hypothyroidism. METHODS: We evaluated thyroid function in 27
patients with cutaneous T-cell lymphoma who were enrolled in trials of high-dose
oral bexarotene at one institution. In addition, we evaluated the in vitro effect
of triiodothyronine, 9-cis-retinoic acid, and the retinoid X receptor-selective
ligand LGD346 on the activity of the thyrotropin beta-subunit gene promoter.
RESULTS: The mean serum thyrotropin concentration declined from 2.2 mU per liter
at base line to 0.05 mU per liter during treatment with bexarotene (P<0.001), and
the mean serum free thyroxine concentration declined from 1.0 ng per deciliter
(12.9 pmol per liter) at base line to 0.45 ng per deciliter (5.8 pmol per liter)
(P<0.001) during treatment. The degree of suppression of thyrotropin secretion
tended to be greater in patients treated with higher doses of bexarotene (>300 mg
per square meter of body-surface area per day) and in those with a history of
treatment with interferon alfa. Nineteen patients had symptoms or signs of
hypothyroidism, particularly fatigue and cold intolerance. The symptoms improved
after the initiation of thyroxine therapy, and all patients became euthyroid
after treatment with bexarotene was stopped. In vitro, LGD346 suppressed the
activity of the thyrotropin beta-subunit gene promoter in thyrotrophs by as much
as 50 percent, an effect similar to that of triiodothyronine and 9-cis-retinoic
acid. CONCLUSIONS: Hypothyroidism may develop in patients with cutaneous T-cell
lymphoma who are treated with high-dose bexarotene, most likely because the
retinoid X receptor-selective ligand suppresses thyrotropin secretion.
PMID- 10194238
TI - Images in clinical medicine. Congenital hemangioma.
PMID- 10194239
TI - Lung transplantation.
PMID- 10194240
TI - Eating disorders.
AB - Eating disorders are common among adolescent girls and young women and are
associated with potentially serious medical complications, yet they often go
undetected and untreated. All patients with eating disorders should be evaluated
and treated for medical complications of the disease at the same time that
psychotherapy and nutritional counseling are undertaken. Pharmacologic agents are
often useful as adjuncts to psychotherapy for bulimia nervosa or binge-eating
disorder; in the case of anorexia nervosa, psychotropic medication is generally
reserved for patients with a concurrent psychiatric illness or those who have
recovered some weight.
PMID- 10194241
TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological
exercises. Case 10-1999. A 53-year-old man with acute renal failure, cortical
blindness, and respiratory distress.
PMID- 10194242
TI - Good news and bad for women with birth defects.
PMID- 10194243
TI - Cytomegalovirus retinitis--evolving therapies in a new era.
PMID- 10194244
TI - Managed care arrives in Latin America.
PMID- 10194246
TI - The exportation of managed care to Latin America.
PMID- 10194247
TI - [A preliminary study of human Y chromosome specific short tandem repeat loci].
AB - OBJECTIVE: To understand the allele structure and reveal genetic polymorphism of
Y chromosome specific short tandem repeat (Y-specific STR) loci in Chinese Han
population. METHODS: The authors used a set of five Y-specific STR loci which
were tetrameric tandem repeat loci chosen from the Genome Database. EDTA-blood
specimens were collected from the unrelated individuals. DNA was extracted by
Chelex method and amplified by the polymerase chain reaction (PCR). The PCR
products were analyzed using both the PAGE horizontal electrophoresis with
discontinuous buffer system and the automated fluorescence detection approach.
RESULTS: The authors observed that the alleles at the five Y-specific STR loci
were composed of some complex repeat structures. They successfully prepared a set
of human allele ladders for the typing of the five Y-specific STRs and
demonstrated the polymorphisms at the five Y-specific STR loci in Chinese Han
population. CONCLUSION: Y-specific STRs are good genetic markers for the purpose
of analysis of genetic relationship between populations. This preliminary study
not only reveals allele frequencies and haplotype distribution of Y-specific STR
in Chinese Han population, but also indicates a reference population for
detecting male migration events and for reconstructing paternal history.
PMID- 10194248
TI - [A comparative study of HLA-A locus in northern and southern Chinese bymeans of
PCR/SSOP typing].
AB - OBJECTIVE: To compare the HLA-A locus in a population selected from Beijing
(northern group) with that in a population selected from Guangzhou (southern
group). METHODS: HLA typing was performed by using PCR/SSOP method. A pair of
primer and 54 probes were used. RESULTS: In 18 alleles identified, the
differences in gene frequency between northern and southern Chinese were found.
In northern group, A*0205, 0210 and 2901 were absent, and the frequencies of
A*2601, 3001 and 3101 were higher than those of southern group; while in southern
group, A*3103, 3201 and 6801 were absent, the frequencies of A*0203 and 1101 were
higher than those of northern group; and in addition, six subtypes of A2
serological specificity, namely A*0201, 0203, 0205, 0206, 0207 and 0210, were
found, in which A*0201 predominated. CONCLUSION: There are some differences in
the genetic background of northern and southern Chinese. A2 subtypes have
important implications for unrelated-donor transplantation.
PMID- 10194249
TI - [Polymorphism of HLA-DRB1, DQB1 in the Hans of north China].
AB - OBJECTIVE: To understand polymorphism of HLA-DRB1, DQB1 in the Hans of north
China and obtain more comprehensive and accurate data on genetics at DNA level.
METHODS: Polymerase chain reaction-sequence specific primers (PCR-SSP) were used
to determine HLA-DRB1, DQB1 alleles in 107 unrelated healthy Han individuals of
north China. RESULTS: The authors determined 14 DRB1, 9 DQB1 alleles, which
included not only the allele frequencies that corresponded to the gene
frequencies of DR, DQ loci determined by other 9 cooperating labs but also the
allele frequencies of DRB1*15, DRB1*16, DQB1*0301, DQB1*0302, DQB1*0303, DQB1*05,
DQB1*0601, DQB1*0602, and DQB1*0604 that other serology labs did not report.
CONCLUSION: This study has obtained a more comprehensive and accurate data set of
the normal allele frequencies and linkage disequilibrium parameters of HLA-DRB1,
DQB1 in the Hans of north China, which may be of significance in the studies on
population genetics and disease association.
PMID- 10194250
TI - [Polymorphisms of five short tandem repeat systems in Chinese Han population in
Chengdu].
AB - OBJECTIVE: To get preliminary genotype and allele frequency distributions of
D6S366, D6S477, D12S375, D12S391 and PLA2A loci in Chinese Han population in
Chengdu area and to validate more short Tandem repeat (STR) systems for forensic
application. METHODS: The polymerase chain reaction (PCR) was used. Five STR
systems (D6S366, D6S477, D12S375, D12S391 and PLA2A) were amplified on DNA
samples, which were extracted from 108 unrelated individuals EDTA-blood by
Phenol/Chloroform method. The PCR products were analyzed by PAG vertical
electrophoresis. RESULTS: Seven alleles were found at D6S366 locus, nine alleles
at D6S477 locus, five alleles at D12S375 locus, nine alleles at D12S391 locus and
seven alleles at PLA2A locus. No deviations from Hardy-Weinberg equilibrium were
observed. The heterozygosities observed were 0.69, 0.78, 0.81, 0.68 and 0.79 for
D6S366, D6S477, D12S375, D12S391 and PLA2A respectively. The chances of exclusion
were 0.3621, 0.6004, 0.4581, 0.7014 and 0.5589 and the discriminating powers were
0.79, 0.93, 0.86, 0.96 and 0.91. CONCLUSION: All of the five loci in this study
were useful markers for individual identification and paternity test and for
genetics purposes.
PMID- 10194251
TI - [Genetic linkage of polymorphisms of type I angiotensin II receptor gene to
Chinese Han hypertension].
AB - OBJECTIVE: To observe the CA repeat polymorphism of the type I angiotensin II
receptor gene on Chinese Han people, and evaluate the genetic linking to
hypertension. METHODS: The CA repeat polymorphism at 3'-flanking region of AT1R
gene was studied by amplified fragment length polymorphism (Amp-FLP ) in Chinese
Han people from Shandong and Xi'an. RESULTS: There were 9 alleles ranging from
130bp to 146bp in all subjects. The allele frequencies were 0.01 to 0.38, and
allele A4 was more frequent in the control. The heterozygosity of CA repeat locus
was 0.789, the polymorphic information content, 0.746. There was no significant
difference in distribution of CA repeat polymorphism genotype between different
regions in same ethnic (P>0. 05), but the allele frequency of CA repeat
polymorphism in hypertensive group was significantly different from that of
control (P<0.05). There was no detectable distortion from Hardy-Weinberg
equilibrium in both groups. CONCLUSION: The results suggest that CA repeat
polymorphism of AT1R gene be associated with Chinese Han hypertensive people.
PMID- 10194252
TI - [HLA-DQA1 genes involved in the genetic susceptibility to duodenal ulcer in Wuhan
Hans].
AB - OBJECTIVE: To study the genetic susceptibility of HLA-DQA1 alleles to duodenal
ulcer in Chinese Hans from Wuhan and its nearby regions. METHODS: Seventy
patients with duodenal ulcer and fifty healthy controls were examined for HLA
DQA1 genotypes. HLA-DQA1 typing was carried out by digesting the locus specific
polymerase chain reaction amplified products with alleles specific restriction
enzymes (PCR-RFLP), Apal I, Basj I, Hph I, Fok I, Mbo II and Mnl I. RESULTS: The
allele frequency of DQA1 0301 in patients with duodenal ulcer (64.3%) was
significantly higher than that in healthy controls (36%). In contrast, the allele
frequency of DQA1 0102 in patients with duodenal ulcer (8.6%) was significantly
lower than that in healthy controls (26%). CONCLUSION: These findings suggest
that DQA1 0301 is a susceptible gene for duodenal ulcer in Wuhan Hans while DQA1
0102 is its resistant gene, and there are immunogenetic differences in HLA-DQA1
locus between duodenal ulcer patients and healthy controls.
PMID- 10194253
TI - [Study on mutation of exon 8 of Wilson's disease gene].
AB - OBJECTIVE: To analyze the frequency of mutation in exon 8 of Wilson's disease
(WD) gene in Chinese people. METHODS: Screening for ATP7B gene mutation was
conducted in 45 WD patients. Mobility shift of exon 8 was analyzed by SSCP.
Nucleotide sequence of exon 8 was analyzed, and the PCR products were cut by
enzyme Msp I. The authors found G2273T mutation at codon 778, and according to
this mutation sequence, made an analysis of enzyme cut by Msp I in all patients.
2 WD families were analyzed. RESULTS: No abnormality was found in 20 controls. In
45 patients, 2 were homozygous (4.4%) and 11 heterozygous (12.2 ). The positive
rate of mutation was 16.67%. The Arg778Leu mutation was validated by this study.
CONCLUSION: The mutation in exon 8 of WD gene may play an important role in
pathogenesis of Wilson's disease in Chinese.
PMID- 10194254
TI - [Missense mutations of exons 14 and 18 of Wilson's disease gene in Chinese
patients].
AB - OBJECTIVE: To investigate the characteristics of mutations of exons 14 and 18 of
Wilson's disease (WD) gene in Chinese patients. METHODS: The subjects of study
included 60 unrelated normal controls and 44 unrelated WD patients. Genomic DNA
was prepared from peripheral blood leukocytes by a salt-out method. Mutations of
exons 14 and 18 in these subjects were screened by polymerase chain reaction
single strand conformation polymorphism (PCR-SSCP) and further confirmed by
sequencing. RESULTS: One patient was homozygous for Arg1041Pro mutation of exon
14 and another patient was heterozygous for Asn1270Ser mutation of exon 18.
CONCLUSION: The mutations of exons 14 and 18 of WD gene in Chinese patients were
confirmed by sequencing for the first time in China. Arg1041Pro was identified as
a novel missense mutation. In addition, an Asn1270Ser, previously described
mutation, was detected in this study. But exons 14 and 18 are not the hot point
mutations of WD gene in Chinese patients.
PMID- 10194255
TI - [The relation between alpha1-antichymotrypsin gene polymorphism and epsilon4
allele of apolipoprotein E gene in Alzheimer disease in Chinese].
AB - OBJECTIVE: To detect the relation between alpha1-antichymotrpsin(AACT)gene
polymorphism and epsilon4 allele of apolipoprotein E (ApoE) gene in Alzheimer
disease (AD) in Chinese. METHODS: The gene polymorphisms of ApoE and AACT were
genotyped in 125 AD cases and 140 controls with PCR methods and RFLP typing. Then
the association between AACT polymorphism and ApoE epsilon4 was analysed.
RESULTS: There was no association between AD and any allele or genotype of AACT
polymorphism; AACT polymorphism was not associated with AD ApoE epsilon4 or
without ApoE epsilon4. In AACT*AT and AACT*TT genotypes, ApoE epsilon4 allele was
associated with AD, but no association was observed in AACT*AA genotype.
CONCLUSION: AACT may not be associated with AD in Chinese, and this effect can
not be influenced by ApoE epsilon4, but AACT gene polymorphism may affect the
association between ApoE epsilon4 allele and AD.
PMID- 10194256
TI - [Study of NAIP gene in spinal muscular atrophy].
AB - OBJECTIVE: Investigating the correlation between the genotype and spinal muscular
atrophy(SMA) clinical phenotype. METHODS: Neuronal apoptosis inhibitory
protein(NAIP) gene analysis was performed by PCR amplification of exon 5 in 13
unrelated SMA patients with deletions of SMN gene. RESULTS: Two Type-I patients(2
M5, 40%) lacked the NAIP exon 5. CONCLUSION: The results suggest a possible
correlation between NAIP gene deletion and the disease severity of SMA.
PMID- 10194257
TI - [Loss of heterozygosity and microsatellite instability in laryngeal carcinoma
near p16 gene].
AB - OBJECTIVE: To search for the minimal overlap region of tumor suppressor gene in
laryngeal carcinoma and discuss the correlation of p16 gene with laryngeal
carcinogenesis. METHODS: Five microsatellite polymorphism markers near p16 gene
were selected to detect loss of heterozygosity (LOH) and microsatellite
instability (MI) in 60 cases of laryngeal squamous cell carcinoma. RESULTS: The
frequencies of LOH in 5 markers were less than 23.1%, while the frequencies of MI
in 2 markers were higher, with the highest frequency (46.1%) in D9S1752.
CONCLUSION: The results suggest that the deletion of p16 gene does not play an
important role in the laryngeal carcinogenesis and there may exist a gene around
D9S1752 participating in the development of laryngeal carcinoma, which correlates
with the mutation of repair gene.
PMID- 10194258
TI - [Influence of aging and sex on chromosome 21 segregation in human lymphocytes].
AB - OBJECTIVE: To determine the influence of aging and sex on the segregation of
chromosome 21. METHODS: Lymphocytes were obtained from healthy donors of
different ages, both sexes, and were treated with cytochalasin B. Binucleated
cells were hybridized with chromosome 21 specific probe, and simultaneously,
chromosome 21 loss and non-disjunction were detected. RESULTS: The coefficients
of correlation between age and binucleated cells containing 4, 2 and 6 signals
were -0.35(P<0.01), 0.18 and 0.38(P<0.01) respectively. The coefficients of
correlation between age and nondisjunction of chromosome 21 and micronuclei were
0.56(P<0.01) and 0.70(P<0.01) respectively. CONCLUSION: There is a significant
increase with age in the number of micronuclei and missegregation. Nondisjunction
of chromosome 21 is much more frequent than loss in vivo and in vitro. No
significant difference in nondisjunctioin between male and female was noted. Age
effect is more significant in female than in male.
PMID- 10194259
TI - [Detection of ABO genotypes by simultaneous PCR-RFLP method].
AB - OBJECTIVE: To study human ABO genotyping by means of multiplex PCR and
restriction fragment length polymorphism. METHODS: Two specific fragments of ABO
gene were simultaneously amplified in a single tube, and then the double
restriction digestion with RE Kpn I and Alu I was performed in the same tube. The
amplified products were analyzed by PAGE and silver staining. A total of 125 Han
unrelated individuals living in Wuhan were genotyped. RESULTS: Six genotypes of
ABO were detected and the distribution was in good agreement with Hardy-Weinberg
equilibrium. CONCLUSION: The results demonstrate that PCR-RFLP based approach is
convenient, reliable and should be of value in forensic application.
PMID- 10194260
TI - [Rapid detection of non-deletional alpha-thalassemia mutations by PCR-LIS-SSCP].
AB - OBJECTIVE: To establish a rapid and convenient single strand conformation
polymorphism (SSCP) analysis method for detecting the point mutation of non
deletional alpha-thalassemia. METHODS: The 543bp DNA fragment spanning the hot
spot region mainly responsible for non-deletional alpha-thalassemia was nested
amplified using the selective amplification of alpha2 globin gene as a template
and was denatured with low ionic strength(LIS) solution followed by SSCP
analysis. RESULTS: LIS buffer was more efficient for ssDNA formation than
formamide buffer was and the formation of ssDNA was very stable. In addition to a
normal electrophoresis pattern, at least three SSCP profiles can be detected by
the present method when the DNA samples bearing non-deletional genes of Hb H
disease were screened. Confirmed by DNA sequencing analysis, the DNAs represented
these profiles have turned out to be the different three mutants, i.e., the
alpha&supCS; mutation, the alpha &supQS; mutation and the alpha&supWestmead;
mutation, respectively. Only 3 hours were needed to complete the electrophoresis
procedure of this method. CONCLUSION: PCR-LIS-SSCP can be used as a tool in rapid
screening for the alterations in human alpha-globin gene.
PMID- 10194261
TI - [Using the method of two-color fluorescence in situ hybridization to detect
aneuploidy of human sperms].
AB - OBJECTIVE: To develop the method of two-color fluorescence in situ hybridization
(FISH) assay and use it for detecting the aneuploidy frequency of human sperm
chromosome. METHODS: Sperm sample was washed three times and the slides were
prepared. The sperm heads were decondensed with dithiothreitol (DTT) and lithium
diiodosalicylate (LIS). Then, the sperm nuclei were hybridized with biotin
labeled alpha satellite X chromosome DNA probe (DXZ1) and digoxigenin labeled
alpha satellite Y chromosome DNA probe (DYZ3). The hybridization signals were
detected with CY3-Streptavidin, goat antistrepavidin for biotin labeled probe and
with mouse antidigoxigenin, rabbit antimouse-FITC for digoxigenin labeled probe.
RESULTS: Under the Nikon fluorescence microscope, the hybridization signals in
the sperm heads were clearly visible. The sperm with one red hybridization signal
was X chromosome sperm (X sperm), and the sperm with one green hybridization
signal in the sperm head was Y chromosome sperm (Y sperm). In the case of two
hybridization signals in one sperm head, the sperm should be a numerical abnormal
one. By using two color FISH with one euchromosome probe and one sex chromosome
probe, the sperm with same color of two hybridization signals in one sperm head
could be identified as aneuploidy sperm or diploid sperm. CONCLUSION: The two
color FISH assay may be used to detect the aneuploidy frequency of human sperms
that were exposed to mutagents and environmental potential aneuoploidogenic
agents.
PMID- 10194276
TI - A study of 1000 malocclusions selected by the HLD (CalMod) Index.
AB - The purpose was to study the results of applying the HLD (CalMod) Index to a very
large population of patients. The materials were the study models of 1000 cases
that had already been measured and approved for treatment. Each model was
remeasured and studied. The average age of the patients was 14.138 years of age;
55% were females and 45% were males. Fifty-six percent were approved on the basis
of a score of 26 or more, and 44% were approved as one of the exceptions in the
index. Fifty-eight percent of the patients were Class I, 35% were Class II, and
7% were Class III. Surprisingly, 26% of all the approvals (19% adjusted for
overlap) were for overjets greater than 9 mm. Reverse overjets occurred at the
rate of 2% of approvals. Deep impinging overbites with tissue destruction
comprised 12% of all approvals and crossbites of individual anterior teeth with
tissue destruction 4%. Only 4 cleft palate cases were recorded, as they do not
routinely enter the system through the index route. No traumatic deviations were
found. The HLD (CalMod) Index has been field tested under a very heavy load. This
study demonstrated that it selects a very wide range of malocclusions.
PMID- 10194277
TI - Efficient and effective indirect bonding.
AB - A new resin designed specifically for indirect bonding has been developed.
Previous problems with indirect bonding systems, which were partly related to the
fact that resins designed for direct bonding had to be used, have been addressed.
A cohesive and complete system for fabricating bonding trays, and the indirect
bonding procedure, is presented.
PMID- 10194278
TI - Condylar cartilage response to continuous passive motion in adult guinea pigs: A
pilot study.
AB - This article reports on the development and testing of a continuous passive
motion device suitable for experimental animals and on the effect of 1 week of
continuous passive motion on the thickness of the condylar cartilage in adult
guinea pigs. Continuous passive motion is currently used for postsurgical joint
therapy and consists of moving a synovial joint passively and constantly through
its normal range of motion. In this study continuous passive motion was applied
to the temporomandibular joints of two experimental animals for 7 hours per day
for 5 days. Two animals were restrained for the same amount of time that the
experimental animals were on the continuous passive motion machines (control
group 1), and two animals were allowed normal cage activity (control group 2).
Six weeks later all animals were sacrificed. Each mandibular condyle was
sectioned sagitally, and routine histologic sections were prepared with
hematoxylin-eosin stain. Microscopic examination of the mandibular condylar
cartilage of the animals placed on continuous passive motion showed a marked
increase in thickness compared with the condylar cartilage found on the control
animals. The condylar cartilage of the animals placed on continuous passive
motion averaged 345 microm, and the controls averaged 232 microm. These findings
demonstrate the application of continuous passive motion in an experimental model
and provide interesting information regarding the response of the mandibular
condyle to increased motion. More studies are necessary to further investigate
the effect of continuous passive motion on the condylar cartilage.
PMID- 10194279
TI - A new accurate approach to the anterior ratio with clinical applications. Part 1:
a computer program.
AB - The arcs of the six anterior maxillary and mandibular teeth have recently been
described mathematically by the hyperbolic cosine function with a maxillary
correlation coefficient (r ) of 0.885 and a mandibular correlation coefficient (r
) of 0.951. Because the geometric relationships of the anterior dental arcs are
known when the occlusion is Class I, a computer program has been developed for
use in clinical practice. Rapid forecasting of the interrelationships between the
maxillary and mandibular arc depths (related to overjet) with variations in the
mesiodistal sums of the six maxillary and mandibular anterior teeth for various
intercanine widths is now possible with ease and accuracy (+/- 0.1 mm). Clinical
applications are illustrated.
PMID- 10194280
TI - Considerations of functional aspects in dentofacial orthopedics and orthodontics:
Sheldon Friel Memorial Lecture.
PMID- 10194281
TI - Accuracy of video imaging for predicting the soft tissue profile after mandibular
set-back surgery.
AB - The purpose of this study was to compare the accuracy of two video-imaging
programs for predicting the soft tissue outcomes of mandibular set-back surgery
for patients with skeletal class III malocclusion. The sample consisted of 30
previously treated, nongrowing, white patients who had undergone isolated
mandibular set-back surgery. An objective comparison was made of each program's
cephalometric prediction using a customized analysis, as well as a subjective
comparison of the predicted images as evaluated by a panel of six raters. The
results showed that both programs produced similar cephalometric and video image
predictions. The cephalometric visual treatment objective predictions were found
to be most accurate in the horizontal plane; approximately 30% of cases showed
errors greater than 2.0 mm, whereas in the vertical plane, the error rate was
greater (50%). The resulting video image predictions were judged by the panel as
being in the "fair" category. A particular problem was noted when significant
vertical compression of the soft tissue images was required. Video imaging was
suitable for patient education but not accurate enough for detailed diagnosis and
treatment planning.
PMID- 10194282
TI - Mechanical properties of several nickel-titanium alloy wires in three-point
bending tests.
AB - The purpose of this study was to clarify the mechanical properties of 42 brands
of nickel-titanium alloy orthodontic wires from 9 manufacturers by conducting
three-point bending tests under uniform testing conditions. Manufacturers
included A-Company, Hoya Medical, Lancer, Ormco, Rocky Mountain, Sankin, Tomy
(GAC), TP, and 3M/Unitek. Cobalt-chrome, and titanium-molybdenum alloy wires were
also tested as a reference for comparison of force levels. All reported data were
recorded during the unloading process to simulate the force that a wire exerts on
a tooth as it is moved into the dental arch from a position of malocclusion. The
following results were obtained for the nickel-titanium wires tested. (1) Among
the 0.016 inch round wires tested under a maximum deflection of 1.5 mm, the
difference between the smallest (Copper nickel-titanium 35) and the largest
(Aline) load values was 136 g. For the 0.016 x 0.022 inch rectangular wires
tested, the difference between the smallest (Copper nickel-titanium 40) and the
largest (Aline) load values was 337 g. (2) The change in load between 1.5 and 0.5
mm of deflection was examined to clarify the superelastic properties of the wires
tested. For the 0.016 inch wires, 17 wire brands produced a load difference of
less than 100 g, and two brands produced a difference of at least 100 g (Aline
and Titanal = 100 g). For the 0.016 x 0.022 inch wires, 15 brands produced a load
difference of less than 100 g, and eight brands produced a difference of over 100
g. The smallest and largest load differences were 3 g (Copper nickel-titanium 35)
and 200 g (Aline). (3) The majority of the samples with a smaller load difference
between deflections of 1.5 mm and 0.5 mm in the unloading process were found
among super-elastic wires, while samples with a larger load difference were
predominantly found among work-hardened wires. Compared with cobalt-chrome and
TMA wires, nickel-titanium alloy wires exert significantly less force. However,
the amount of force varies greatly from brand to brand. Consequently, when using
nickel-titanium alloy wires, brands must be selected carefully by taking into
consideration the severity of the malocclusion and the stage of orthodontic
treatment in each case. It is the intent of this study to offer clinicians an
unbiased guide for the selection of appropriate nickel-titanium alloy wires.
PMID- 10194283
TI - Congenitally missing second premolars in cleft lip and cleft palate children.
AB - Panoramic and periapical radiographs of 278 patients with cleft lip, cleft
palate, or both (158 males and 120 females), age 5 to 18 years, were examined to
determine the frequency of missing second premolars and the possible association
between the cleft side and the side from which the premolar was absent. The
prevalence (18%) of missing premolars found in this study is significantly higher
than is found in the general population. A considerably higher incidence of
missing second premolars was found in the maxilla compared with the mandible both
for unilateral and bilateral missing teeth. The second premolar was absent more
frequently on the left than on the right side, both in males and females and in
both jaws. Interestingly but consistent with our previous reporting, this
corresponded to the side where clefts occurred more often. The cause of the
higher prevalence of left-sided clefts and missing second premolars in human
beings is not known at the present time.
PMID- 10194284
TI - Three-dimensional dental arch curvature in human adolescents and adults.
AB - The three-dimensional arrangement of dental cusps and incisal edges in human
dentitions has been reported to fit the surface of a sphere (the curve of
Monson), with a radius of about 4 inches in adults. The objective of the current
study was to compare the three-dimensional curvature of the mandibular dental
arch in healthy permanent dentitions of young adults and adolescents. The
mandibular casts of 50 adults (aged 19 to 22 years) and 20 adolescents (aged 12
to 14 years) with highly selected sound dentitions that were free from
temporomandibular joint problems were obtained. The three coordinates of cusp
tips excluding the third molars were digitized with a three-dimensional
digitizer, and used to derive a spherical model of the curvature of the occlusal
surfaces. From the best interpolating sphere, the radii of the left and right
curves of Spee (quasi-sagittal plane) and of molar curve of Wilson (frontal
plane) were computed. Mandibular arch size (interdental distances) was also
calculated. The occlusal curvature of the mandibular arch was not significantly
influenced by sex, although a significant effect of age was found (Student t, P
<.005). The radii of the overall sphere, right and left curves of Spee, and curve
of Wilson in the molar area were about 101 mm in adults, and about 80 mm in
adolescents. Arch size was not influenced by either sex or age. The different
curvatures of the occlusal plane in adolescents and adults may be explained by a
progressive rotation of the major axis of the teeth moving the occlusal plane
toward a more buccal position. These dental movements should be performed in a
frontal plane on an anteroposterior axis located next to the dental crown.
PMID- 10194285
TI - Treatment of an impacted dilacerated maxillary central incisor.
AB - Impacted Incisor With Dilaceration refers to a dental deformity characterized by
an angulation between crown and root causing noneruption of the incisor. Surgical
extraction used to be the first choice in treating the severely dilacerated
incisor. In this article, a horizontally impacted and dilacerated maxillary
central incisor was diagnosed radiographically. By combining two stages of the
crown exposure surgery with light force orthodontic traction, the impacted
dilacerated incisor was successfully moved into proper position. However, long
term monitoring of the stability and periodontal health is critical after
orthodontic traction.
PMID- 10194286
TI - Asymmetric extraction treatment of a Class II Division 1 subdivision left
malocclusion with anterior and posterior crossbites.
PMID- 10194287
TI - Correction of a severe Class II Division 1 malocclusion with bilateral buccal
crossbite.
PMID- 10194288
TI - Site-specific subgingival colonization by Actinobacillus actinomycetemcomitans in
orthodontic patients.
AB - A high prevalence of Actinobacillus actinomycetemcomitans (Aa) in subgingival
plaque in patients for orthodontia already has been observed. The present study
had the following aims: 1) to ascertain a direct relationship between the
orthodontic appliance placement and the subgingival colonization by Aa, and 2) to
determine whether the Aa growth specifically occurred on teeth with braces
attached or whether the presence of orthodontic appliances could also cause the
isolation of Aa in teeth free from therapeutic appliances. Twenty-four young
systemically and periodontally healthy subjects with malaligned and crowded teeth
in the anterior sextants of both dental arches participated in this study. After
1 session of ultrasonic scaling with oral hygiene instructions during the first
experimental session, the mesiobuccal sites of the first molars and the
distobuccal sites of the lateral incisors in both dental arches in each
participant were subjected to clinical and microbiologic examination for the
recovery of Aa. Clinical examination consisted of recording the presence of
plaque and the examination of gingival bleeding on probing and probing depth.
Microbiologic sampling was obtained with the insertion of 3 sterile paper points
at the deepest part of each gingival sulcus. Altogether, 192 periodontal sites
were examined. After the examinations, the patients received fixed orthodontic
appliances in only 1 dental arch (test sites) and the other one was left free
from appliances (control sites). Clinical examination and microbiologic sampling
were repeated in the same experimental test and control sites after 4, 8, and 12
weeks. At the 12-week session, the orthodontic appliance was removed from the
test arch, and, 4 weeks later, a further clinical and microbiologic examination
was performed. The results showed that, during the period with orthodontic
appliances, the presence of plaque scores and the gingival bleeding on probing
scores were increased significantly and that Aa, initially absent from all but 1
subject, was isolated in 19 and 20 subjects after 4 and 8 weeks, respectively.
Furthermore, no gingival sites from the control teeth (free from Aa colonization
at baseline) showed positive results for the sought-after bacterium throughout
the entire length of the study. It was concluded that the placement of
orthodontic appliances promotes the subgingival growth of Aa; this specific
microbial change is specifically restricted to subgingival plaque from
orthodontic appliance-bearing teeth. The presence of orthodontic bands and
brackets therefore cannot affect the microbiologic condition of the whole mouth.
PMID- 10194289
TI - Treatment and posttreatment effects of acrylic splint Herbst appliance therapy.
AB - This study evaluated the skeletal and dentoalveolar changes induced by acrylic
splint Herbst therapy of Class II malocclusion. The treated group comprised 55
subjects with Class II malocclusion treated with the acrylic splint Herbst
appliance followed by comprehensive edgewise therapy. The mean age at Time 1
(immediately before treatment) was 12 years and 10 months +/- 1 year and 2
months. The mean age at Time 2 (immediately after debonding of the Herbst
appliance) and Time 3 (posttreatment) was 13 years and 10 months +/- 1 year and 2
months and 15 years and 2 months +/- 1 year and 4 months, respectively. The two
control groups were one group of 30 subjects with untreated Class II malocclusion
and another group of 33 subjects with Class I occlusion. The three groups were
homogeneous as to the stage of maturation of cervical vertebrae at all
observation times. A modification of Pancherz's cephalometric analysis was
applied to the lateral cephalograms of the three groups at Time 1, Time 2, and
Time 3. Linear and angular measurements for mandibular dimensions, cranial base
angulation, and vertical relationships were added to the original analysis.
Differences for all the variables from Time 1 to Time 2 (active treatment
effects), from Time 2 to Time 3 (posttreatment effects), and from Time 1 to Time
3 (overall treatment effects) were calculated for the treated group and
contrasted to corresponding differences of both untreated groups by means of
ANOVA (P <.05). The study showed that two thirds of the achieved occlusal
correction was due to skeletal effects and only one third to dentoalveolar
adaptations. Both skeletal and dentoalveolar effects were due mainly to changes
in mandibular structures. A significant amount of relapse in molar relationship
occurred during the posttreatment period, and this change could be ascribed to
the mesial movement of the upper molars.
PMID- 10194290
TI - An evaluation of factors affecting duration of orthodontic treatment.
AB - One of the first questions asked by new orthodontic patients is: How long will I
need to wear my braces? A multitude of factors have the potential to influence
the answer to this question. The purpose of this retrospective study was to
identify some of the primary factors that influence orthodontic treatment
duration. Few studies have attempted to evaluate these factors. Data were
gathered from 140 consecutively completed, comprehensive treatment patient
records in five orthodontic offices. Thirty-one variables related to patient
characteristics, diagnostic factors, modality of treatment, and patient
cooperation were evaluated. Average treatment time was 28.6 months with a range
of 23.4 to 33.4 months among the five offices. Nearly half (46.9%) of the
variation in treatment duration was explained by a five-step multiple regression
analysis. Included in the regression equation were the number of missed
appointments, the number of replaced brackets and bands, the number of treatment
phases, the number of negative chart entries regarding oral hygiene, and the
prescription of headgear wear during treatment. An additional 6.7% of the
variance was explained by variation among the five offices. Six of the 31
variables examined made a statistically significant (alpha =.01) contribution to
the explanation of variation in treatment time. The quality of the finished cases
and the appropriateness of the original diagnosis and treatment plan were not
evaluated. Developing an objective assessment to evaluate these areas may be
important for increasing our understanding of treatment time variation.
PMID- 10194291
TI - Mandibular distraction osteogenesis: a historic perspective and future
directions.
AB - Although orthognathic surgery has gained a generalized acceptance for
maxillomandibular deformity correction, several limitations are associated with
acute advancement of osteotomized bone segments. Furthermore, large skeletal
discrepancies, such as those seen in syndromic patients, require such extensive
bone movements that the surrounding soft tissues will not adapt to their new
position, resulting in relapse or compromised function and esthetics. Recently, a
number of experimental and clinical investigations have demonstrated that gradual
mechanical traction of bone segments at an osteotomy site created in the
craniofacial region can generate new bone parallel to the direction of traction.
This phenomenon, known as distraction osteogenesis, opens up new possibilities in
the correction of craniofacial deformities by orthodontists and maxillofacial
surgeons. Hence, the purpose of this article is to review the historic
development and biologic foundation of mandibular distraction osteogenesis,
critically evaluate the current mandibular distraction devices with their
clinical applications, and predict the future evolution of mandibular
osteodistraction techniques.
PMID- 10194292
TI - Morphing and warping. Part I.
PMID- 10194294
TI - Eli lilly award in biological chemistry pfizer award in enzyme chemistry and
repligen corporation award in chemistry of biological processes nominations
solicited
PMID- 10194293
TI - Litigation, legislation, and ethics. Ethics case analysis: the ethics of
terminating care because of financial delinquency.
PMID- 10194295
TI - Multiple conformations of the acylenzyme formed in the hydrolysis of methicillin
by Citrobacter freundii beta-lactamase: a time-resolved FTIR spectroscopic study.
AB - Time-resolved infrared difference spectroscopy has been used to show that the
carbonyl group of the acylenzyme reaction intermediate in the Citrobacter
freundii beta-lactamase-catalyzed hydrolysis of methicillin can assume at least
four conformations. A single-turnover experiment shows that all four
conformations decline during deacylation with essentially the same rate constant.
The conformers are thus in exchange on the reaction time scale, assuming that
deacylation takes place only from the conformation which is most strongly
hydrogen bonded or from a more minor species not visible in these experiments.
All conformers have the same (10 cm-1) narrow bandwidth compared with a model
ethyl ester in deuterium oxide (37 cm-1) which shows that all conformers are well
ordered relative to free solution. The polarity of the carbonyl group environment
in the conformers varies from 'ether-like' to strongly hydrogen bonding (20
kJ/mol), presumably in the oxyanion hole of the enzyme. From the absorption
intensities, it is estimated that the conformers are populated approximately
proportional to the hydrogen bonding strength at the carbonyl oxygen. A change in
the difference spectrum at 1628 cm-1 consistent with a perturbation (relaxation)
of protein beta-sheet occurs slightly faster than deacylation. Consideration of
chemical model reactions strongly suggests that neither enamine nor imine
formation in the acyl group is a plausible explanation of the change seen at 1628
cm-1. A turnover reaction supports the above conclusions and shows that the
conformational relaxation occurs as the substrate is exhausted and the
acylenzymes decline. The observation of multiple conformers is discussed in
relation to the poor specificity of methicillin as a substrate of this beta
lactamase and in terms of X-ray crystallographic structures of acylenzymes where
multiple forms are not apparently observed (or modeled). Infrared spectroscopy
has shown itself to be a useful method for assessment of the uniqueness of enzyme
substrate interactions in physiological turnover conditions as well as for
determination of ordering, hydrogen bonding, and protein perturbation.
PMID- 10194296
TI - Origin of the transient electron paramagnetic resonance signals in DNA
photolyase.
AB - DNA photolyase repairs pyrimidine dimer lesions in DNA through light-induced
electron donation to the dimer. During isolation of the enzyme, the flavin
cofactor necessary for catalytic activity becomes one-electron-oxidized to a
semiquinone radical. In the absence of external reducing agents, the flavin can
be cycled through the semiquinone radical to the fully reduced state with light
induced electron transfer from a nearby tryptophan residue. This cycle provides a
convenient means of studying the process of electron transfer within the protein
by using transient EPR. By studying the excitation wavelength dependence of the
time-resolved EPR signals we observe, we show that the spin-polarized EPR signal
reported earlier from this laboratory as being initiated by semiquinone
photochemistry actually originates from the fully oxidized form of the flavin
cofactor. Exciting the semiquinone form of the flavin produces two transient EPR
signals: a fast signal that is limited by the time response of the instrument and
a slower signal with a lifetime of approximately 6 ms. The fast component appears
to correlate with a dismutation reaction occurring with the flavin. The longer
lifetime process occurs on a time scale that agrees with transient absorption
data published earlier; the magnetic field dependence of the amplitude of this
kinetic component is consistent with redox chemistry that involves electron
transfer between flavin and tryptophan. We also report a new procedure for the
rapid isolation of DNA photolyase.
PMID- 10194297
TI - Evidence for a regulatory role of cholesterol superlattices in the hydrolytic
activity of secretory phospholipase A2 in lipid membranes.
AB - We have conducted a detailed study of the effect of membrane cholesterol content
on the initial hydrolytic activity of Crotalus durissus terrificus venom
phospholipase A2 (sPLA2) in large unilamellar vesicles of cholesterol/dimyristoyl
L-alpha-phosphatidylcholine (DMPC) and cholesterol/1-palmitoyl-2-oleoyl-L-alpha
phosphatidylcholine (POPC) at 37 degrees C. The activity was monitored by using
the acrylodan-labeled intestinal fatty acid binding protein and HPLC. In contrast
to conventional approaches, we have used small cholesterol concentration
increments ( approximately 0.3-1.0 mol %) over a wide concentration range (e.g.,
13-54 mol % cholesterol). In both membrane systems examined, the initial
hydrolytic activity of sPLA2 is found to change with cholesterol content in an
alternating manner. The activity reaches a local minimum when the membrane
cholesterol content is at or near the critical cholesterol mole fractions (e.g.,
14.3, 15.4, 20.0, 22.2, 25.0, 33.3, 40.0, and 50.0 mol % cholesterol) predicted
for cholesterol regularly distributed in either hexagonal or centered rectangular
superlattices. According to the sterol regular distribution model [Chong, P. L.
G. (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 10069-10073; Liu et al. (1997)
Biophys. J. 72, 2243-2254], the extent of lipid superlattices is maximal at the
critical cholesterol mole fractions, at which the membrane free volume is
minimal. Thus, our present data can be taken to indicate that the initial
hydrolytic activity of sPLA2 is governed by the extent of cholesterol
superlattice. These data provide the first functional evidence for the formation
of cholesterol superlattices in both saturated (e.g., DMPC) and unsaturated
(e.g., POPC) liquid-crystalline phospholipid bilayers. The data also illustrate
the functional importance of cholesterol superlattice and demonstrate a new type
of regulation of sPLA2. Furthermore, upon binding to cholesterol/POPC large
unilamellar vesicles, the intrinsic fluorescence intensity of sPLA2 shows an
alternating variation with cholesterol content, exhibiting a minimum at the
critical cholesterol mole fractions. This result suggests that either the number
of sPLA2 bound to lipid vesicles or the conformation of membrane-bound sPLA2 or
both vary with the extent of the cholesterol superlattice in the plane of the
membrane.
PMID- 10194298
TI - NMR solution structure of alpha-conotoxin ImI and comparison to other conotoxins
specific for neuronal nicotinic acetylcholine receptors.
AB - Alpha-Conotoxins, peptides produced by predatory species of Conus marine snails,
are potent antagonists of nicotinic acetylcholine receptors (nAChRs), ligand
gated ion channels involved in synaptic transmission. We determined the NMR
solution structure of the smallest known alpha-conotoxin, ImI, a 12 amino acid
peptide that binds specifically to neuronal alpha7-containing nAChRs in mammals.
Calculation of the structure was based on a total of 80 upper distance
constraints and 31 dihedral angle constraints resulting in 20 representative
conformers with an average pairwise rmsd of 0.44 A from the mean structure for
the backbone atoms N, Calpha, and C' of residues 2-11. The structure of ImI is
characterized by two compact loops, defined by two disulfide bridges, which form
distinct subdomains separated by a deep cleft. Two short 310-helical regions in
the first loop are followed by a C-terminal beta-turn in the second. The two
disulfide bridges and Ala 9 form a rigid hydrophobic core, orienting the other
amino acid side chains toward the surface. Comparison of the three-dimensional
structure of ImI to those of the larger, 16 amino acid alpha-conotoxins PnIA,
PnIB, MII, and EpI-also specific for neuronal nAChRs-reveals remarkable
similarity in local backbone conformations and relative solvent-accessible
surface areas. The core scaffold is conserved in all five conotoxins, whereas the
residues in solvent-exposed positions are highly variable. The second helical
region, and the specific amino acids that the helix exposes to solvent, may be
particularly important for binding and selectivity. This comparative analysis
provides a three-dimensional structural basis for interpretation of mutagenesis
data and structure-activity relationships for ImI as well other neuronal alpha
conotoxins.
PMID- 10194299
TI - NF-kappa B binding mechanism: a nuclear magnetic resonance and modeling study of
a GGG --> CTC mutation.
AB - We present the solution structure of the nonpalindromic 16 bp DNA
5'd(CTGCTCACTTTCCAGG)3'. 5'd(CCTGGAAAGTGAGCAG)3' containing a mutated kappaB site
for which the mutation of a highly conserved GGG tract of the native kappaB HIV-1
site to CTC abolishes NF-kappaB binding. 1H and 31P NMR spectroscopies have been
used together with molecular modeling to determine the fine structure of the
duplex. NMR data show evidence for a BI-BII equilibrium of the CpA.TpG steps at
the 3'-end of the oligomer. Models for the extreme conformations reached by the
mutated duplex (denoted 16M) are proposed in agreement with the NMR data. Since
the distribution of BII sites is changed in the mutated duplex compared to that
of the native duplex (denoted 16N), large differences are induced in the
intrinsic structural properties of both duplexes. In particular, in BII
structures, 16M shows a kink located at the 3'-end of the duplex, and in
contrast, 16N exhibits an intrinsic global curvature toward the major groove.
Whereas 16N can reach a conformation very favorable for the interaction with NF
kappaB, 16M cannot mimic such a conformation and, moreover, its deeper and
narrower major groove could hinder the DNA-protein interactions.
PMID- 10194300
TI - Catalase HPII from Escherichia coli exhibits enhanced resistance to denaturation.
AB - Catalase HPII from Escherichia coli is a homotetramer of 753 residue subunits.
The multimer displays a number of unusual structural features, including
interwoven subunits and a covalent bond between Tyr415 and His392, that would
contribute to its rigidity and stability. As the temperature of a solution of
HPII in 50 mM potassium phosphate buffer (pH 7) is raised from 50 to 92 degrees
C, the enzyme begins to lose activity at 78 degrees C and 50% inactivation has
occurred at 83 degrees C. The inactivation is accompanied by absorbance changes
at 280 and 407 nm and by changes in the CD spectrum consistent with small changes
in secondary structure. The subunits in the dimer structure remain associated at
95 degrees C and show a significant level of dissociation only at 100 degrees C.
The exceptional stability of the dimer association is consistent with the
interwoven nature of the subunits and provides an explanation for the resistance
to inactivation of the enzyme. For comparison, catalase-peroxidase HPI of E. coli
and bovine liver catalase are 50% inactivated at 53 and 56 degrees C,
respectively. In 5.6 M urea, HPII exhibits a coincidence of inactivation, CD
spectral change, and dissociation of the dimer structure with a midpoint of 65
degrees C. The inactive mutant variants of HPII which fold poorly during
synthesis and which lack the Tyr-His covalent bond undergo spectral changes in
the 78 to 84 degrees C range, revealing that the extra covalent linkage is not
important in the enhanced resistance to denaturation and that problems in the
folding pathway do not affect the ultimate stability of the folded structure.
PMID- 10194301
TI - Site-directed mutagenesis of phosphate-contacting amino acids of bovine
pancreatic deoxyribonuclease I.
AB - Bovine pancreatic deoxyribonuclease I (DNase I) is an endonuclease which cleaves
double-stranded DNA. Cocrystal structures of DNase I with oligonucleotides have
revealed interactions between the side chains of several amino acids (N74, R111,
N170, S206, T207, and Y211) and the DNA phosphates. The effects these
interactions have on enzyme catalysis and DNA hydrolysis selectivity have been
investigated by site-directed mutagenesis. Mutations to R111, N170, T207, and
Y211 severely compromised activity toward both DNA and a small chromophoric
substrate. A hydrogen bond between R111 (which interacts with the phosphate
immediately 5' to the cutting site) and the essential amino acid H134 is probably
required to maintain this histidine in the correct orientation for efficient
hydrolysis. Both T207 and Y211 bind to the phosphate immediately 3' to the
cleavage site. Additionally, T207 is involved in binding an essential,
structural, calcium ion, and Y211 is the nearest neighbor to D212, a critical
catalytic residue. N170 interacts with the scissile phosphate and appears to play
a direct role in the catalytic mechanism. The mutation N74D, which interacts with
a phosphate twice removed from the scissile group, strongly reduced DNA
hydrolysis. However, a comparison of DNase I variants from several species
suggests that certain amino acids, which allow interaction with phosphates
(positively charged or hydrogen bonding), are tolerated. S206, which binds to a
DNA phosphate two positions away from the cleavage site, appears to play a
relatively unimportant role. None of the enzyme variants, including a triple
mutation in which N74, R111, and Y211 were altered, affected DNA hydrolysis
selectivity. This suggests that phosphate binding residues play no role in the
selection of DNA substrates.
PMID- 10194302
TI - Photoaffinity labeling with the activator IMP and site-directed mutagenesis of
histidine 995 of carbamoyl phosphate synthetase from Escherichia coli demonstrate
that the binding site for IMP overlaps with that for the inhibitor UMP.
AB - Photoaffinity labeling with IMP was used to attach covalently this activator to
its binding site of Escherichia coli carbamoyl phosphate synthetase. We now
identify histidine 995 of the large enzyme subunit as the amino acid that is
cross-linked with IMP. The identification was carried out by comparative peptide
mapping in two chromatographic systems of peptides differentially labeled with
[3H]IMP and with the labeled inhibitor [14C]UMP, followed by automated Edman
degradation and radiosequence analysis. Site-directed substitution of His995 by
alanine confirmed His995 to be the only amino acid in the protein forming a
covalent adduct with IMP. The His995Ala mutant protein was soluble and active and
exhibited normal kinetics for the activator ornithine and for the substrates in
the presence of ornithine. However, the mutation selectively induced changes in
the activation by IMP and the inhibition by UMP, and it abolished the
photolabeling of the enzyme by IMP without affecting the photolabeling by the
inhibitor UMP. Since UMP is cross-linked to Lys993 [Cervera, J., et al. (1996)
Biochemistry 35, 7247-7255] only two residues upstream of the site of IMP
labeling, the results provide structural evidence for earlier proposals which
suggested that UMP and IMP bind in a single or overlapping site. The two residues
are within the region previously proposed as the binding fold for the nucleotide
effectors. In the crystal structure of the enzyme, Lys993 and His995 are exposed
and line a crevice where a Pi molecule was found [Thoden, J. B., et al. (1997)
Biochemistry 36, 6305-6316]. UMP and IMP appear to bind in this crevice, possibly
toward the C-side of the beta-sheet in a Rossman fold. Their binding in this site
is consistent with the selectivity of adduct formation of UMP with Lys993 and of
IMP with His995. It is also consistent with the nonessentiality of His995 for the
binding, since the interactions with other residues that line the crevice must
contribute a large part of the binding energy. The lack of an effect of the
mutation on the activation by ornithine is consistent with the binding of this
activator in a separate site in the protein.
PMID- 10194303
TI - Hydrogen bonding and equilibrium protium-deuterium fractionation factors in the
immunoglobulin G binding domain of protein G.
AB - Protium-deuterium fractionation factors (phi) were determined for more than 85%
of the backbone amide protons in the IgG binding domains of protein G, GB1 and
GB2, from NMR spectra recorded over a range of H2O/D2O solvent ratios. Previous
studies suggest a correlation between phi and hydrogen bond strength; amide and
hydroxyl groups in strong hydrogen bonds accumulate protium (phi < 1), while weak
hydrogen bonds accumulate deuterium (phi > 1). Our results show that the alpha
helical residues have slightly lower phi values (1.03 +/- 0.05) than beta-sheet
residues (1.12 +/- 0.07), on average. The lowest phi value obtained (0.65) does
not involve a backbone amide but rather is for the interaction between two side
chains, Y45 and D47. Fractionation factors for solvent-exposed residues are
between the alpha-helix and beta-sheet values, on average, and are close to those
for random coil peptides. Further, the difference in phiav between alpha-helix
and solvent-exposed residues is small, suggesting that differences in hydrogen
bond strength for intrachain hydrogen bonds and amide...water hydrogen bonds are
also small. Overall, the enrichment for deuterium suggests that most
backbone...backbone hydrogen bonds are weak.
PMID- 10194304
TI - Structural independence of ligand-binding modules five and six of the LDL
receptor.
AB - The low-density lipoprotein receptor (LDLR) is the primary mechanism for the
uptake of plasma cholesterol into cells and serves as a prototype for a growing
family of cell surface receptors. These receptors all utilize tandemly repeated
LDL-A modules to bind their ligands. Each LDL-A module is about 40 residues long,
has six conserved cysteine residues, and contains a conserved acidic region near
the C-terminus which serves as a calcium-binding site. The structure of the
interface presented for ligand binding by these modules, and the basis for their
specificity and affinity in ligand binding, is not yet known. We have purified
recombinant molecules corresponding to LDL-A modules five (LR5), six (LR6), and
the module five-six pair (LR5-6) of the LDL receptor. Calcium is required to
establish native disulfide bonds and to maintain the structural integrity of LR5,
LR6, and the LR5-6 module pair. Folding studies of the I189D and D206Y mutations
within LR5 indicate that each change leads to misfolding of the module,
explaining the previous observation that each of these changes mimics the
functional effect of deletion of the entire module [Russell, D. W., Brown, M. S.,
and Goldstein, J. L. (1989) J. Biol. Chem. 264, 21682-21688]. By fluorescence,
the affinity of LR5 for calcium, which is crucial for folding and function of
these modules, remains approximately 40 nM whether LR6 is attached. Comparison of
proton and multidimensional heteronuclear NMR spectra of individual modules to
those of the module pair indicates that most of the significant spectroscopic
changes lie within the linker region between modules and that little structural
interaction occurs between the cores of modules five and six in the 5-6 pair.
These findings strongly support a model in which each module is essentially
structurally independent of the other.
PMID- 10194305
TI - Analysis of the functional coupling between calmodulin's calcium binding and
peptide recognition properties.
AB - The enhancement of calmodulin's (CaM) calcium binding activity by an enzyme or a
recognition site peptide and its diminution by key point mutations at the protein
recognition interface (e.g., E84K-CaM), which is more than 20 A away from the
nearest calcium ligation structure, can be described by an expanded version of
the Adair-Klotz equation for multiligand binding. The expanded equation can
accurately describe the calcium binding events and their variable linkage to
protein recognition events can be extended to other CaM-regulated enzymes and can
potentially be applied to a diverse array of ligand binding systems with
allosteric regulation of ligand binding, whether by other ligands or protein
interaction. The 1.9 A resolution X-ray crystallographic structure of the complex
between E84K-CaM and RS20 peptide, the CaM recognition site peptide from
vertebrate smooth muscle and nonmuscle forms of myosin light chain kinase,
provides insight into the structural basis of the functional communication
between CaM's calcium ligation structures and protein recognition surfaces. The
structure reveals that the complex adapts to the effect of the functional
mutation by discrete adjustments in the helix that contains E84. This helix is on
the amino-terminal side of the helix-loop-helix structural motif that is the
first to be occupied in CaM's calcium binding mechanism. The results reported
here are consistent with a sequential and cooperative model of CaM's calcium
binding activity in which the two globular and flexible central helix domains are
functionally linked, and provide insight into how CaM's calcium binding activity
and peptide recognition properties are functionally coupled.
PMID- 10194306
TI - Biochemical characterization of mono(ADP-ribosyl)ated poly(ADP-ribose)
polymerase.
AB - Here, we report the biochemical characterization of mono(ADP-ribosyl)ated
poly(ADP-ribose) polymerase (PARP) (EC 2.4.2. 30). PARP was effectively mono(ADP
ribosyl)ated both in solution and via an activity gel assay following SDS-PAGE
with 20 microM or lower concentrations of [32P]-3'-dNAD+ as the ADP-ribosylation
substrate. We observed the exclusive formation of [32P]-3'-dAMP and no polymeric
ADP-ribose molecules following chemical release of enzyme-bound ADP-ribose units
and high-resolution polyacrylamide gel electrophoresis. The reaction in solution
(i) was time-dependent, (ii) was activated by nicked dsDNA, and (iii) increased
with the square of the enzyme concentration. Stoichiometric analysis of the
reaction indicated that up to four amino acid residues per mole of enzyme were
covalently modified with single units of 3'-dADP-ribose. Peptide mapping of
mono(3'-dADP-ribosyl)ated-PARP following limited proteolysis with either papain
or alpha-chymotrypsin indicated that the amino acid acceptor sites for chain
initiation with 3'-dNAD+ as a substrate are localized within an internal 22 kDa
automodification domain. Neither the amino-terminal DNA-binding domain nor the
carboxy-terminal catalytic fragment became ADP-ribosylated with [32P]-3'-dNAD+ as
a substrate. Finally, the apparent rate constant of mono(ADP-ribosyl)ation in
solution indicates that the initiation reaction catalyzed by PARP proceeds 232
fold more slowly than ADP-ribose polymerization.
PMID- 10194307
TI - Depolymerization of phospholamban in the presence of calcium pump: a fluorescence
energy transfer study.
AB - Phospholamban (PLB), a 52-amino acid protein, regulates the Ca-ATPase (calcium
pump) in cardiac sarcoplasmic reticulum (SR) through PLB phosphorylation mediated
by beta-adrenergic stimulation. The mobility of PLB on SDS-PAGE indicates a
homopentamer, and it has been proposed that the pentameric structure of PLB is
important for its regulatory function. However, the oligomeric structure of PLB
must be determined in its native milieu, a lipid bilayer containing the Ca
ATPase. Here we have used fluorescence energy transfer (FET) to study the
oligomeric structure of PLB in SDS and dioleoylphosphatidylcholine (DOPC) lipid
bilayers reconstituted in the absence and presence of Ca-ATPase. PLB was labeled,
specifically at Lys 3 in the cytoplasmic domain, with amine-reactive fluorescent
donor/acceptor pairs. FET between donor- and acceptor-labeled subunits of PLB in
SDS solution and DOPC lipid bilayers indicated the presence of PLB oligomers. The
dependence of FET efficiency on the fraction of acceptor-labeled PLB in DOPC
bilayers indicated that it is predominantly an oligomer having 9-11 subunits,
with approximately 10% of the PLB as monomer, and the distance between dyes on
adjacent PLB subunits is 0.9 +/- 0.1 nm. When labeled PLB was reconstituted with
purified Ca-ATPase, FET indicated the depolymerization of PLB into smaller
oligomers having an average of 5 subunits, with a concomitant increase in the
fraction of monomer to 30-40% and a doubling of the intersubunit distance. We
conclude that PLB exists primarily as an oligomer in membranes, and the Ca-ATPase
affects the structure of this oligomer, but the Ca-ATPase binds preferentially to
the monomer and/or small oligomers. These results suggest that the active
inhibitory species of PLB is a monomer or an oligomer having fewer than 5
subunits.
PMID- 10194308
TI - Replication protein A interactions with DNA. 1. Functions of the DNA-binding and
zinc-finger domains of the 70-kDa subunit.
AB - Human replication protein A (RPA) is a multiple subunit single-stranded DNA
binding protein that is required for multiple processes in cellular DNA
metabolism. This complex, composed of subunits of 70, 32, and 14 kDa, binds to
single-stranded DNA (ssDNA) with high affinity and participates in multiple
protein-protein interactions. The 70-kDa subunit of RPA is known to be composed
of multiple domains: an N-terminal domain that participates in protein
interactions, a central DNA-binding domain (composed of two copies of a ssDNA
binding motif), a putative (C-X2-C-X13-C-X2-C) zinc finger, and a C-terminal
intersubunit interaction domain. A series of mutant forms of RPA were used to
elucidate the roles of these domains in RPA function. The central DNA-binding
domain was necessary and sufficient for interactions with ssDNA; however,
adjacent sequences, including the zinc-finger domain and part of the N-terminal
domain, were needed for optimal ssDNA-binding activity. The role of aromatic
residues in RPA-DNA interactions was examined. Mutation of any one of the four
aromatic residues shown to interact with ssDNA had minimal effects on RPA
activity, indicating that individually these residues are not critical for RPA
activity. Mutation of the zinc-finger domain altered the structure of the RPA
complex, reduced ssDNA-binding activity, and eliminated activity in DNA
replication.
PMID- 10194309
TI - Replication protein A interactions with DNA. 2. Characterization of double
stranded DNA-binding/helix-destabilization activities and the role of the zinc
finger domain in DNA interactions.
AB - Human replication protein A (RPA) is a heterotrimeric single-stranded DNA-binding
protein that is composed of subunits of 70, 32, and 14 kDa. RPA is required for
multiple processes in cellular DNA metabolism. RPA has been reported to (1) bind
with high affinity to single-stranded DNA (ssDNA), (2) bind specifically to
certain double-stranded DNA (dsDNA) sequences, and (3) have DNA helix
destabilizing ("unwinding") activity. We have characterized both dsDNA binding
and helix destabilization. The affinity of RPA for dsDNA was lower than that of
ssDNA and precisely correlated with the melting temperature of the DNA fragment.
The rates of helix destabilization and dsDNA binding were similar, and both were
slow relative to the rate of binding ssDNA. We have previously mapped the regions
required for ssDNA binding [Walther et al. (1999) Biochemistry 38, 3963-3973].
Here, we show that both helix-destabilization and dsDNA-binding activities map to
the central DNA-binding domain of the 70-kDa subunit and that other domains of
RPA are needed for optimal activity. We conclude that all types of RPA binding
are manifestations of RPA ssDNA-binding activity and that dsDNA binding occurs
when RPA destabilizes a region of dsDNA and binds to the resulting ssDNA. The 70
kDa subunit of all RPA homologues contains a highly conserved putative (C-X2-C
X13-C-X2-C) zinc finger. This motif directly interacts with DNA and contributes
to dsDNA-binding/unwinding activity. Evidence is presented that a metal ion is
required for the function of the zinc-finger motif.
PMID- 10194310
TI - 2'-deoxyribonolactone lesion in DNA: refined solution structure determined by
nuclear magnetic resonance and molecular modeling.
AB - The solution conformation of the DNA duplex
d(C1G2C3A4C5L6C7A8C9G10C11).d(G12C13G14T15G16T17G18T19G20C21G22 ) containing the
2'-deoxyribonolactone lesion (L6) in the middle of the sequence has been
investigated by NMR spectroscopy and restrained molecular dynamics calculations.
Interproton distances have been obtained by complete relaxation matrix analysis
of the NOESY cross-peak intensities. These distances, along with torsion angles
for sugar rings and additional data derived from canonical A- and B-DNA, have
been used for structure refinement by restrained molecular dynamics (rMD). Six
rMD simulations have been carried out starting from both regular A- and B-DNA
forms. The pairwise rms deviations calculated for each refined structure are <1
A, indicating convergence to essentially the same geometry. The accuracy of the
rMD structures has been assessed by complete relaxation matrix back-calculation.
The average sixth-root residual index (Rx = 0.052 +/- 0.003) indicated that a
good fit between experimental and calculated NOESY spectra has been achieved.
Detailed analysis revealed a right-handed DNA conformation for the duplex in
which both the T17 nucleotide opposite the abasic site and the lactone ring are
located inside the helix. No kinking is observed for this molecule, even at the
abasic site step. This structure is compared to that of the oligonucleotide with
the identical sequence containing the stable tetrahydrofuran abasic site analogue
that we reported previously [Coppel, Y., Berthet, N., Coulombeau, C., Coulombeau,
Ce., Garcia, J., and Lhomme, J. (1997) Biochemistry 36, 4817-4830].
PMID- 10194311
TI - Coupling of transcription and translation in Dictyostelium discoideum nuclei.
AB - The nuclei of Dictyostelium discoideum cells have been found to contain
polyribosomes active in protein synthesis. mRNA molecules enter nuclear
polyribosomes while they are still being synthesized. "Non sense mediated mRNA
decay" occurs in the nucleus, through the interaction of the mRNAs containing a
nonsense codon with newly formed nuclear ribosomes, rather than with cytoplasmic
ribosomes, as previously generally supposed.
PMID- 10194312
TI - Subsets of the zinc finger motifs in dsRBP-ZFa can bind double-stranded RNA.
AB - dsRBP-ZFa is a Xenopus zinc finger protein that binds dsRNA and RNA-DNA hybrids
with high affinity and in a sequence-independent manner. The protein consists of
a basic N-terminal region with seven C2H2 zinc finger motifs and an acidic C
terminal region that is not required for binding. The last four zinc finger
motifs, and the linkers that join them, are nearly identical repeats, while the
first three motifs and their linkers are each unique. To identify which regions
of the protein are involved in nucleic acid binding, we examined the ability of
five protein fragments to bind dsRNA and RNA-DNA hybrids. Our studies reveal that
a fragment encompassing the three N-terminal, unique zinc finger motifs and
another encompassing the last three of the nearly identical motifs have binding
properties similar to the full-length protein. Since these two fragments do not
share zinc finger motifs of the same sequence, dsRBP-ZFa must contain more than
one type of zinc finger motif capable of binding dsRNA. As with the full-length
protein, ssRNA and DNA do not significantly compete for dsRNA binding by the
fragments.
PMID- 10194313
TI - Stability of the dimerization domain effects the cooperative DNA binding of short
peptides.
AB - The basic region peptide derived from the basic leucine zipper protein GCN4 bound
specifically to the native GCN4 binding sequences in a dimeric form when the beta
cyclodextrin/adamantane dimerization domain was introduced at the C-terminus of
the GCN4 basic region peptide. We describe here how the structure and stability
of the dimerization domain affect the cooperative formation of the peptide dimer
DNA complex. The basic region peptides with five different guest molecules were
synthesized, and their equilibrium dissociation constants with a peptide
possessing beta-cyclodextrin were determined. These values, ranging from 1.3 to
15 microM, were used to estimate the stability of the complexes between the
dimers with various guest/cyclodextrin dimerization domains and GCN4 target
sequences. An efficient cooperative formation of the dimer complexes at the GCN4
binding sequence was observed when the adamantyl group was replaced with the
norbornyl or noradamantyl group, but not with the cyclohexyl group that formed a
beta-cyclodextrin complex with a stability that was 1 order of magnitude lower
than that of the adamantyl group. Thus, cooperative formation of the stable dimer
DNA complex appeared to be effected by the stability of the dimerization domain.
For the peptides that cooperatively formed dimer-DNA complexes, there was no
linear correlation between the stability of the inclusion complex and that of the
dimer-DNA complex. With the beta-cyclodextrin/adamantane dimerization domain, the
basic region peptide dimer preferred to bind to a palindromic 5'-ATGACGTCAT-3'
sequence over the sequence lacking the central G.C base pair and that with an
additional G.C base pair in the middle. Changing the adamantyl group into a
norbornyl group did not alter the preferential binding of the peptide dimers to
the palindromic sequence, but slightly affected the selectivity of the dimer for
other nonpalindromic sequences. The helical contents of the peptides in the DNA
bound dimer with the adamantyl group were decreased by reducing the stability of
the dimer-DNA complex, which was possibly caused by deformation of the helical
structure proximal to the dimerization domain.
PMID- 10194314
TI - Raman markers of nonaromatic side chains in an alpha-helix assembly: Ala, Asp,
Glu, Gly, Ile, Leu, Lys, Ser, and Val residues of phage fd subunits.
AB - The study of filamentous virus structure by Raman spectroscopy requires accurate
band assignments. In previous work, site- and residue-specific isotope
substitutions were implemented to elucidate definitive assignments for Raman
bands arising from vibrational modes of the alpha-helical coat protein main chain
and aromatic side chains in the class I filamentous phage, fd [Overman, S. A.,
and Thomas, G. J., Jr. (1995) Biochemistry 34, 5440-5451; Overman, S. A., and
Thomas, G. J., Jr. (1998) Biochemistry 37, 5654-5665]. Here, we extend the
previous methods and expand the assignment scheme to identify Raman markers of
nonaromatic side chains of the coat protein in the native fd assembly. This has
been accomplished by Raman analysis of 11 different fd isotopomers selectively
incorporating deuterium at specific sites in either alanine, aspartic acid,
glutamic acid, glycine, isoleucine, leucine, lysine, serine, or valine residues
of the coat protein. Raman markers are also identified for the corresponding
deuterated side chains. In combination with previous assignments, the results
provide a comprehensive understanding of coat protein contributions to the Raman
signature of the fd virion and validate Raman markers assigned to the packaged
single-stranded DNA genome. The findings described here show that nonaromatic
side chains contribute prolifically to the fd Raman signature, that marker bands
for specific nonaromatics differ in general from those observed in corresponding
polypeptides and amino acids, and that the frequencies and intensities of many
nonaromatic markers are sensitive to secondary and higher-order structures.
Nonaromatic markers within the 1200-1400 cm-1 interval also interfere seriously
with the diagnostic Raman amide III band that is normally exploited in secondary
structure analysis. Implications of these findings for the assessment of protein
conformation by Raman spectroscopy are considered.
PMID- 10194315
TI - Plasmid DNA cleavage by MunI restriction enzyme: single-turnover and steady-state
kinetic analysis.
AB - Mutational analysis has previously indicated that D83 and E98 residues are
essential for DNA cleavage activity and presumably chelate a Mg2+ ion at the
active site of MunI restriction enzyme. In the absence of metal ions, protonation
of an ionizable residue with a pKa > 7.0, most likely one of the active site
carboxylates, controls the DNA binding specificity of MunI [Lagunavicius, A.,
Grazulis, S., Balciunaite, E., Vainius, D., and Siksnys, V. (1997) Biochemistry
36, 11093-11099.]. Thus, competition between H+ and Mg2+ binding at the active
site of MunI presumably plays an important role in catalysis/binding. In the
present study we have identified elementary steps and intermediates in the
reaction pathway of plasmid DNA cleavage by MunI and elucidated the effect of pH
and Mg2+ ions on the individual steps of the DNA cleavage reaction. The kinetic
analysis indicated that the multiple-turnover rate of plasmid cleavage by MunI is
limited by product release throughout the pH range 6.0-9.3. Quenched-flow
experiments revealed that open circle DNA is an obligatory intermediate in the
reaction pathway. Under optimal reaction conditions, open circle DNA remains
bound to the MunI; however it is released into the solution at low [MgCl2]. Rate
constants for the phoshodiester bond hydrolysis of the first (k1) and second (k2)
strand of plasmid DNA at pH 7.0 and 10 mM MgCl2 more than 100-fold exceed the
kcat value which is limited by product dissociation. The analysis of the pH and
[Mg2+] dependences of k1 and k2 revealed that both H+ and Mg2+ ions compete for
the binding to the same residue at the active site of MunI. Thus, the decreased
rate of phosphodiester hydrolysis by MunI at pH < 7.0 may be due to the reduction
of affinity for the Mg2+ binding at the active site. Kinetic analysis of DNA
cleavage by MunI yielded estimates for the association-dissociation rate
constants of enzyme-substrate complex and demonstrated the decreased stability of
the MunI-DNA complex at pH values above 8.0.
PMID- 10194316
TI - Regulation of catalytic activity and processivity of human telomerase.
AB - The ends of eukaryotic chromosomes are specialized sequences, called telomeres
comprising tandem repeats of simple DNA sequences. Those sequences are essential
for preventing aberrant recombination and protecting genomic DNA against
exonucleolytic DNA degradation. Telomeres are maintained at a stable length by
telomerase, an RNA-dependent DNA polymerase. Recently, human telomerase has been
recognized as a unique diagnostic marker for human tumors and is potentially a
highly selective target for antitumor drugs. In this study, we have examined the
major factors affecting the catalytic activity and processivity of human
telomerase. Specifically, both the catalytic activity and processivity of human
telomerase were modulated by temperature, substrate (dNTP and primer)
concentration, and the concentration of K+. The catalytic activity of telomerase
increased as temperature (up to 37 degrees C), concentrations of dGTP, primer,
and K+ were increased. However, the processivity of human telomerase decreased as
temperature, primer concentration, and K+ were increased. Our results support the
current model for human telomerase reaction and strengthen the hypothesis that a
G-quadruplex structure of telomere DNA plays an important role in the regulation
of the telomerase reaction.
PMID- 10194317
TI - Chitin oligosaccharide synthesis by rhizobia and zebrafish embryos starts by
glycosyl transfer to O4 of the reducing-terminal residue.
AB - Lipochitin oligosaccharides are organogenesis-inducing signal molecules produced
by rhizobia to establish the formation of nitrogen-fixing root nodules in
leguminous plants. Chitin oligosaccharide biosynthesis by the Mesorhizobium loti
nodulation protein NodC was studied in vitro using membrane fractions of an
Escherichia coli strain expressing the cloned M. loti nodC gene. The results
indicate that prenylpyrophosphate-linked intermediates are not involved in the
chitin oligosaccharide synthesis pathway. We observed that, in addition to N
acetylglucosamine (GlcNAc) from UDP-GlcNAc, NodC also directly incorporates free
GlcNAc into chitin oligosaccharides. Further analysis showed that free GlcNAc is
used as a primer that is elongated at the nonreducing terminus. The synthetic
glycoside p-nitrophenyl-beta-N-acetylglucosaminide (pNPGlcNAc) has a free
hydroxyl group at C4 but not at C1 and could also be used as an acceptor by NodC,
confirming that chain elongation by NodC takes place at the nonreducing-terminal
residue. The use of artificial glycosyl acceptors such as pNPGlcNAc has not
previously been described for a processive glycosyltransferase. Using this
method, we show that also the DG42-directed chitin oligosaccharide synthase
activity, present in extracts of zebrafish embryos, is able to initiate chitin
oligosaccharide synthesis on pNPGlcNAc. Consequently, chain elongation in chitin
oligosaccharide synthesis by M. loti NodC and zebrafish DG42 occurs by the
transfer of GlcNAc residues from UDP-GlcNAc to O4 of the nonreducing-terminal
residue, in contrast to earlier models on the mechanism of processive beta
glycosyltransferase reactions.
PMID- 10194318
TI - Identification of the 16S rRNA m5C967 methyltransferase from Escherichia coli.
AB - The fmu gene product has been proposed to be an RNA methyltransferase [Koonin, E.
V. (1994) Nucleic Acids Res. 22, 2476-2478]. Fmu has been cloned and expressed,
and the encoded 47 kDa protein has been purified and characterized. The enzyme
catalyzed specific methylation of C967 of unmodified 16S rRNA transcripts. A
16mer stem-loop structure containing C967 (nt 960-975) was also a good substrate
for the enzyme in vitro. Methylation of C967 was confirmed by several methods
including analysis of RNase T1 digests and nearest-neighbor analysis. Fmu did not
catalyze methylation of transcripts of 23S rRNA. E. coli cells that contained
kanr-disrupted fmu produced 16S rRNA that could be specifically methylated by Fmu
in vitro at C967 but not C1407. Further, fmu disruption did not significantly
alter the growth rate of E. coli in rich or minimal media. We propose renaming
this ORF "rrmB" and the enzyme "RrmB" for rRNA methyltransferase.
PMID- 10194319
TI - Evidence for a two-base mechanism involving tyrosine-265 from arginine-219
mutants of alanine racemase.
AB - A positively charged residue, R219, was found to interact with the pyridine
nitrogen of pyridoxal phosphate in the structure of alanine racemase from
Bacillus stearothermophilus [Shaw et al. (1997) Biochemistry 36, 1329-1342].
Three site-directed mutants, R219K, R219A, and R219E, have been characterized and
compared to the wild type enzyme (WT) to investigate the role of R219 in
catalysis. The R219K mutation is functionally conservative, retaining
approximately 25% of the WT activity. The R219A and R219E mutations decrease
enzyme activity by approximately 100- and 1000-fold, respectively. These results
demonstrate that a positively charged residue at this position is required for
efficient catalysis. R219 and Y265 are connected through H166 via hydrogen bonds.
The R219 mutants exhibit similar kinetic isotope effect trends: increased primary
isotope effects (1.5-2-fold) but unchanged solvent isotope effects in the L --> D
direction and increased solvent isotope effects (1.5-2-fold) but unchanged
primary isotope effects in the D --> L direction. These results support a two
base racemization mechanism involving Y265 and K39. They additionally suggest
that Y265 is selectively perturbed by R219 mutations through the H166 hydrogen
bond network. pH profiles show a large pKa shift from 7.1-7.4 (WT and R219K) to
9. 5-10.4 (R219A and R219E) for kcat/KM, and from 7.3 to 9.9-10.4 for kcat. The
group responsible for this ionization is likely to be the phenolic hydroxyl of
Y265, whose pKa is electrostatically perturbed in the WT by the H166-mediated
interaction with R219. Accumulation of an absorbance band at 510 nm, indicative
of a quinonoid intermediate, only in the D --> L direction with R219E provides
additional evidence for a two-base mechanism involving Y265.
PMID- 10194320
TI - 3'-Phosphoadenosine 5'-phosphosulfate binding site of flavonol 3-sulfotransferase
studied by affinity chromatography and 31P NMR.
AB - The function of Lys-59, Arg-141, and Arg-277 in PAPS binding and catalysis of the
flavonol 3-sulfotransferase was investigated. Affinity chromatography of
conservative mutants with PAPS analogues allowed us to determine that Lys-59
interacts with the 5' portion of the nucleotide, while Arg-141 interacts with the
3' portion, confirming assignments deduced from the crystal structure of mouse
estrogen sulfotransferase [Kakuta, Y., Pedersen, L. G., Carter, C. W. , Negishi,
M., and Pedersen, L. C. (1997) Nat. Struct. Biol. 4, 904-908]. The affinity
chromatography method could be used to characterize site-directed mutants for
other types of enzymes that bind nucleoside 3',5'- or 2',5'-diphosphates. 31P NMR
spectra of enzyme-PAP complexes were recorded for the wild-type enzyme and K59R
and K59A mutants. The results of these experiments suggest that Lys-59 is
involved in the determination of the proper orientation of the phosphosulfate
group for catalysis.
PMID- 10194321
TI - Dual-mode EPR study of new signals from the S3-state of oxygen-evolving complex
in photosystem II.
AB - The light-induced new EPR signals at g = 12 and 8 were observed in photosystem II
(PS II) membranes by parallel polarization EPR. The signals were generated after
two flashes of illumination at room temperature, and the signal intensity had
four flashes period oscillation, indicating that the signal origin could be
ascribed to the S3-state. Successful simulations were obtained assuming S = 1
spin for the values of the zero-field parameters, D = +/-0.435 +/- 0. 005 cm-1
and E/D = -0.317 +/- 0.002. Orientation dependence of the g =12 and 8 signal
intensities shows that the axial direction of the zero-field interaction of the
manganese cluster is nearly parallel to the membrane normal.
PMID- 10194322
TI - Identification of metal-binding residues in the Klebsiella aerogenes urease
nickel metallochaperone, UreE.
AB - The urease accessory protein encoded by ureE from Klebsiella aerogenes is
proposed to bind intracellular Ni(II) for transfer to urease apoprotein. While
native UreE possesses a histidine-rich region at its carboxyl terminus that binds
several equivalents of Ni, the Ni-binding sites associated with urease activation
are internal to the protein as shown by studies involving truncated H144UreE
[Brayman and Hausinger (1996) J. Bacteriol. 178, 5410-5416]. Nine potential Ni
binding residues (five His, two Cys, one Asp, and one Tyr) within H144UreE were
independently substituted by mutagenesis to determine their roles in metal
binding and urease activation. In vivo effects of these substitutions on urease
activity were measured in Escherichia coli strains containing the K. aerogenes
urease gene cluster with the mutated ureE genes. Several mutational changes led
to reductions in specific activity, with substitution of His96 producing urease
activity below the level obtained from a ureE deletion mutant. The metal-binding
properties of purified variant UreE proteins were characterized by a combination
of equilibrium dialysis and UV/visible, EPR, and hyperfine-shifted 1H NMR
spectroscopic methods. Ni binding was unaffected for most H144UreE variants, but
mutant proteins substituted at His110 or His112 exhibited greatly reduced
affinity for Ni and bound one, rather than two, metal ions per dimer. Cys79 was
identified as the Cu ligand responsible for the previously observed charge
transfer transition at 370 nm, and His112 also was shown to be associated with
this chromophoric site. NMR spectroscopy provided clear evidence that His96 and
His110 serve as ligands to Ni or Co. The results from these and other studies, in
combination with prior spectroscopic findings for metal-substituted UreE [Colpas
et al. (1998) J. Biol. Inorg. Chem. 3, 150-160], allow us to propose that the
homodimeric protein possesses two nonidentical metal-binding sites, each
symmetrically located at the dimer interface. The first equivalent of added Ni or
Co binds via His96 and His112 residues from each subunit of the dimer, and two
other N or O donors. Asp111 either functions as a ligand or may affect this site
by secondary interactions. The second equivalent of Ni or Co binds via the
symmetric pair of His110 residues as well as four other N or O donors. In
contrast, the first equivalent of Cu binds via the His110 pair and two other N/O
donors, while the second equivalent of Cu binds via the His112 pair and at least
one Cys79 residue. UreE sequence comparisons among urease-containing
microorganisms reveal that residues His96 and Asp111, associated with the first
site of Ni binding, are highly conserved, while the other targeted residues are
missing in many cases. Our data are most compatible with one Ni-binding site per
dimer being critical for UreE's function as a metallochaperone.
PMID- 10194323
TI - Redox reactivity of animal apoferritins and apoheteropolymers assembled from
recombinant heavy and light human chain ferritins.
AB - The redox reactivities of air-oxidized apo horse spleen ferritin (HoSF) and apo
rat liver ferritin (RaF) were examined by microcoulometry and reductive optical
titrations. Microcoulometry on several independent lots of commercial HoSF
revealed two distinct types of redox activity: one requiring 3-4 electrons and
one requiring 6-7 electrons for full reduction of the protein shell. ApoRaF
required 8-9 electrons to fully reduce the oxidized form. Reductive optical
titrations confirmed the microcoulometric reduction stoichiometry and, in
addition, showed that the spectra of both oxidized and reduced apoHoSF were
distinct and possessed absorbances tailing into the visible region. The redox
reactivity of both apoRaF and apoHoSF correlated with their H-subunit
composition. Identical microcoulometric and optical experiments were conducted
with recombinant apo human liver heavy (rHuHF) and light (rHuLF) ferritins, but
neither was redox-active. These results suggest that the redox reactivity of
native ferritins is due to their heteropolymeric nature. This was confirmed by
mixing various proportions of rHuHF and rHuLF, dissociating the 24-mers into
individual subunits with guanidine hydrochloride at pH 3.5, and renaturing to
form heteropolymeric 24-mers. Microcoulometric measurements of these
apoheteropolymers reassembled in vitro showed that they were redox-active like
their native apoheteropolymer counterparts. The redox activity of these
apoheteropolymers increased with H-subunit composition, reached a maximum near 12
H- and 12 L-subunits, and then declined to zero with increasing L-subunit
composition. The decline in redox reactivity at high L-subunit concentrations
indicates that both H- and L-subunits are involved in forming the observed redox
centers. Apoheteropolymers formed from rHuLF and W93F (an H-chain mutant) were
redox-inactive, suggesting that the conserved tryptophan is necessary for redox
center formation.
PMID- 10194324
TI - Bilin organization in cryptomonad biliproteins.
AB - The bilin organization of three cryptomonad biliproteins (phycocyanins 612 and
645 and phycoerythrin 545) was examined in detail. Two others (phycocyanin 630
and phycoerythrin 566) were studied less extensively. Phycocyanin 645 and
phycoerythrin 545 were suggested to have one bilin in each monomeric (alphabeta)
unit of the dimer (alpha2beta2) isolated from the others, and the remaining six
bilins may be in pairs. One pair was found across the monomer-monomer interface
of the protein dimer, and two identical pairs were proposed to be within the
monomer protein units. For phycocyanin 612, a major surprise was that a pair of
bilins was apparently not found across the monomer-monomer interface, but the
remaining bilins were distributed as in the other two cryptomonad proteins. The
effect of temperature on the CD spectra of phycocyainin 612 demonstrated that two
of the bands (one positive and one negative) behaved identically, which is
required if they are coupled. The two lowest-energy CD bands of phycocyanin 612
originated from paired bilins, and the two higher-energy bands were from more
isolated bilins. The paired bilins within the protein monomers contained the
lowest-energy transition for these biliproteins. Using the bilins as naturally
occurring reporter groups, phycocyanin 612 was shown to undergo a reversible
change in tertiary structure at 40 degrees C. Protein monomers were shown to be
functioning biliproteins. A hypothesis is that the coupled pair of bilins within
the monomeric units offers important advantages for efficient energy migration,
and other bilins transfer energy to this pair, extending the wavelength range or
efficiency of light absorption.
PMID- 10194325
TI - Catalytic acid/base residues of glutamate racemase.
AB - Glutamate racemase is a cofactor-independent enzyme that employs two active-site
cysteine residues as acid/base catalysts during the interconversion of glutamate
enantiomers. In a given reaction direction, a thiolate from one of the cysteines
abstracts the alpha-proton, and the other cysteine thiol delivers a proton to the
opposite face of the resulting carbanionic intermediate. This paper reports that
the C73S and C184S mutants are still capable of racemizing glutamate with
specificity constants about 10(3)-fold lower than those of the wild-type enzyme.
A "one-base requiring" reaction, the elimination of water from N
hydroxyglutamate, has been used to deduce which thiol acts as the base for a
given enantiomer. With D-N-hydroxyglutamate the C73S mutant is a much poorer
catalyst than wild-type enzyme, whereas the C184S mutant is a somewhat better
catalyst. This trend was reversed with L-N-hydroxyglutamate, suggesting that
Cys73 is responsible for the deprotonation of D-glutamate and Cys184 is
responsible for the deprotonation of L-glutamate. In addition, with C73S the
Vmax/KM isotope effect on D-glutamate racemization was greater than that seen
with wild-type enzyme, whereas the isotope effect with L-glutamate had decreased.
The results were reversed with the C184S mutant. This is interpreted as being due
to an asymmetry in the free energy profiles that is induced upon mutation, with
the deprotonation step involving a serine becoming the more cleanly rate
determining of the two. These results support the above assignment and the notion
that a carbanionic intermediate is formed during catalysis.
PMID- 10194326
TI - Derivatization of the interface cysteine of triosephosphate isomerase from
Trypanosoma brucei and Trypanosoma cruzi as probe of the interrelationship
between the catalytic sites and the dimer interface.
AB - In the interface of homodimeric triosephosphate isomerase from Trypanosoma brucei
(TbTIM) and Trypanosoma cruzi (TcTIM), one cysteine of each monomer forms part of
the intersubunit contacts. The relatively slow derivatization of these cysteines
by sulfhydryl reagents induces progressive structural alterations and abolition
of catalysis [Garza-Ramos et al. (1998) Eur. J. Biochem. 253, 684-691].
Derivatization of the interface cysteine by 5, 5-dithiobis(2-nitrobenzoate)
(DTNB) and methylmethane thiosulfonate (MMTS) was used to probe if events at the
catalytic site are transmitted to the dimer interface. It was found that enzymes
in the active catalytic state are significantly less sensitive to the thiol
reagents than in the resting state. Maximal protection against derivatization of
the interface cysteine by thiol reagents was obtained at near-saturating
substrate concentrations. Continuous recording of derivatization by DTNB showed
that catalysis hinders the reaction of sulfhydryl reagents with the interface
cysteine. Therefore, in addition to intrinsic structural barriers, catalysis
imposes additional impediments to the action of thiol reagents on the interface
cysteine. In TcTIM, the substrate analogue phosphoglycolate protected strongly
against DTNB action, and to a lesser extent against MMTS action; in TbTIM,
phosphoglycolate protected against the effect of DTNB, but not against the action
of MMTS. This indicates that barriers of different magnitude to the reaction of
thiol reagents with the interface cysteine are induced by the events at the
catalytic site. Studies with a Cys14Ser mutant of TbTIM confirmed that all the
described effects of sulfhydryl reagents on the trypanosomal enzymes are a
consequence of derivatization of the interface cysteine.
PMID- 10194327
TI - Transition state of the rate-limiting step of heat denaturation of Cry3A delta
endotoxin.
AB - Heat denaturation of Cry3A delta-endotoxin from Bacillus thuringiensis var.
tenebrionis and its 55 kDa fragment was studied by differential scanning
microcalorimetry at low pH. Analysis of the calorimetric data has shown that
denaturation of Cry3A delta-endotoxin is a nonequilibrium process at heating
rates from 0. 125 to 2 K/min. This means that the stability of delta-endotoxin
(the apparent temperature of denaturation Tm) under these conditions is under
kinetic control rather than under thermodynamic control. It has been shown that
heat denaturation of this protein is a one-step kinetic process. The enthalpy of
the process and its activation energy were measured as functions of temperature.
The data obtained allow confirmation of the fact that the conformation of delta
endotoxin at the transition state only slightly differs from its native
conformation with respect to compactness and extent of hydration. The comparison
of the activation energy for intact delta-endotoxin and the 55 kDa fragment
showed that the transition of the molecule to a transition state does not cause
any changes in the conformation of three N-terminal alpha-helices. Complete
removal of the N-terminal domain of delta-endotoxin and 40 amino acids from the C
terminus beta-sheet domain III causes an irreversible loss of the tertiary
structure. Thus, during protein folding the nucleation core determining protein
stability does not involve its three initial alpha-helices but may include the
remaining alpha-helices of the N-terminal domain. The functional significance of
peculiarities of structure arrangement of the delta-endotoxin molecule is
discussed.
PMID- 10194328
TI - Nativelike structure and stability in a truncation mutant of a protein
minidomain: the peripheral subunit-binding domain.
AB - Despite its small size, the peripheral subunit-binding domain from the
dihydrolipoamide acetyltransferase component of the Bacillus stearothermophilus
pyruvate dehydrogenase multienzyme complex adopts a unique, compact structure. To
determine whether the full 43 residue sequence is required for the domain to
adopt a stable, nativelike structure, 3 proteins of different lengths were
prepared. Psbd41 corresponds to residues 3-43 of the domain, psbd36 spans
residues 6-41, and psbd33 comprises residues 7-39. Psbd41 folds in a cooperative,
two-state fashion with a Tm of 53 degrees C and a stability at 25 degrees C of
2.2 kcal mol-1. Psbd36 is nearly as stable with a Tm of 48 degrees C and a
stability of 1.8 kcal mol-1. Similar m-values and heat capacities suggest that
psbd36 and psbd41 bury approximately the same surface area. Minimal differences
in CalphaH and NH chemical shifts between psbd41 and psbd36 show that the two
sequences adopt the same tertiary fold. On a per residue basis, DeltaH degrees
and DeltaC degrees p fall within the range typical for single-domain globular
proteins. Psbd33 is significantly less stable. It is not fully folded at 25
degrees C, and at all temperatures it shows broadened NMR lines. ANS titrations
provide evidence that this is due to an equilibrium between nativelike and
unfolded molecules rather than formation of a molten globule. The fraction of
psbd33 molecules which are folded appear to adopt the same structure as the full
length domain. Thus, although more than the 33 residue core is required to form a
fully stable native structure, the entire sequence is not required for folding.
PMID- 10194329
TI - Interactions of amyloid beta-peptide (1-40) with ganglioside-containing
membranes.
AB - Interactions between amyloid beta-peptides (Abeta) and neuronal membranes have
been postulated to play an important role in the neuropathology of Alzheimer's
disease. To gain insight into the molecular details of this association, we
investigated the interactions of Abeta (1-40) with ganglioside-containing
membranes by circular dichroism (CD) and Fourier transform infrared-polarized
attenuated total reflection (FTIR-PATR) spectroscopy. The CD study revealed that
at physiological ionic strength Abeta (1-40) specifically binds to ganglioside
containing membranes inducing a two-state, unordered --> beta-sheet transition
above a threshold intramembrane ganglioside concentration, which depends on the
host lipid bilayers used. Furthermore, differences in the number and position of
sialic acid residues of the carbohydrate backbone significantly affected the
conformational transition of the peptide. FTIR-PATR spectroscopy experiments
demonstrated that Abeta (1-40) forms an antiparallel beta-sheet, the plane of
which lies parallel to the membrane surface, inducing dehydration of lipid
interfacial groups and perturbation of acyl chain orientation. These results
suggest that Abeta (1-40) imposes negative curvature strain on ganglioside
containing lipid bilayers, disturbing the structure and function of the
membranes.
PMID- 10194330
TI - Intestinal absorption of dietary cholesteryl ester is decreased but retinyl ester
absorption is normal in carboxyl ester lipase knockout mice.
AB - Carboxyl ester lipase (CEL; EC 3.1.1.13) hydrolyzes cholesteryl esters and
retinyl esters in vitro. In vivo, pancreatic CEL is thought to liberate
cholesterol and retinol from their esters prior to absorption in the intestine.
CEL is also a major lipase in the breast milk of many mammals, including humans
and mice, and is thought to participate in the processing of triglycerides to
provide energy for growth and development while the pancreas of the neonate
matures. Other suggested roles for CEL include the direct facilitation of the
intestinal absorption of free cholesterol and the modification of plasma
lipoproteins. Mice with different CEL genotypes [wild type (WT), knockout
(CELKO), heterozygote] were generated to study the functions of CEL in a
physiological system. Mice grew and developed normally, independent of the CEL
genotype of the pup or nursing mother. Consistent with this was the normal
absorption of triglyceride in CELKO mice. The absorption of free cholesterol was
also not significantly different between CELKO (87 +/- 26%, mean +/- SD) and WT
littermates (76 +/- 10%). Compared to WT mice, however, CELKO mice absorbed only
about 50% of the cholesterol provided as cholesteryl ester (CE). There was no
evidence for the direct intestinal uptake of CE or for intestinal bacterial
enzymes that hydrolyze it, suggesting that another enzyme besides CEL can
hydrolyze dietary CE in mice. Surprisingly, CELKO and WT mice absorbed similar
amounts of retinol provided as retinyl ester (RE). RE hydrolysis, however, was
required for absorption, implying that CEL was not the responsible enzyme. The
changes in plasma lipid and lipoprotein levels to diets with increasing lipid
content were similar in mice of all three CEL genotypes. Overall, the data
indicate that in the mouse, other enzymes besides CEL participate in the
hydrolysis of dietary cholesteryl esters, retinyl esters, and triglycerides.
PMID- 10194331
TI - Carboxyl ester lipase overexpression in rat hepatoma cells and CEL deficiency in
mice have no impact on hepatic uptake or metabolism of chylomicron-retinyl ester.
AB - To study the role of carboxyl ester lipase (CEL) in hepatic retinoid (vitamin A)
metabolism, we investigated uptake and hydrolysis of chylomicron (CM)-retinyl
esters (RE) by rat hepatoma (McArdle-RH7777) cells stably transfected with a rat
CEL cDNA. We also studied tissue uptake of CM-RE in CEL-deficient mice generated
by targeted disruption of the CEL gene. CEL-transfected cells secreted active
enzyme into the medium. However, both control and CEL-transfected cells
accumulated exogenously added CM-RE or CM remnant (CMR)-derived RE in equal
amounts. Serum clearance of intravenously injected CM-RE and cholesteryl ester
were not different between wild-type and CEL-deficient mice. Also, the uptake of
the two compounds by the liver and other tissues did not differ. These data
indicate that the lack of CEL expression does not affect the uptake of dietary CM
RE by the liver or other tissues. Moreover, the percentage of retinol formed in
the liver after CM-RE uptake, the levels of retinol and retinol-binding protein
in serum, and retinoid levels in various tissues did not differ, indicating that
CEL deficiency does not affect hepatic retinoid metabolism and retinoid
distribution throughout the body. Surprisingly, in both pancreas and liver of
wild-type, heterozygous, and homozygous CEL-deficient mice, the levels of bile
salt-dependent retinyl ester hydrolase (REH) activity were similar. This
indicates that in the mouse pancreas and liver an REH enzyme activity, active in
the presence of bile salt and distinct from CEL, is present, compatible with the
results from our accompanying paper that the intestinal processing and absorption
of RE were unimpaired in CEL-deficient mice.
PMID- 10194332
TI - Exploring the temperature-pressure phase diagram of staphylococcal nuclease.
AB - The temperature dependence of the pressure-induced equilibrium unfolding of
staphylococcal nuclease (Snase) was determined by fluorescence of the single
tryptophan residue, FTIR absorption for the amide I' and tyrosine O-H bands, and
small-angle X-ray scattering (SAXS). The results from these three techniques were
similar, although the stability as measured by fluorescence was slightly lower
than that measured by FTIR and SAXS. The resulting phase diagram exhibits the
well-known curvature for heat and cold denaturation of proteins, due to the large
decrease in heat capacity upon folding. The volume change for unfolding became
less negative with increasing temperatures, consistent with a larger thermal
expansivity for the unfolded state than for the folded state. Fluorescence
detected pressure-jump kinetics measurements revealed that the curvature in the
phase diagram is due primarily to the rate constant for folding, indicating a
loss in heat capacity for the transition state relative to the unfolded state.
The similar temperature dependence of the equilibrium and activation volume
changes for folding indicates that the thermal expansivities of the folded and
transition states are similar. This, along with the fact that the activation
volume for folding is positive over the temperature range examined, the nonlinear
dependence of the folding rate constant upon temperature implicates significant
dehydration in the rate-limiting step for folding of Snase.
PMID- 10194333
TI - DnaJ dramatically stimulates ATP hydrolysis by DnaK: insight into targeting of
Hsp70 proteins to polypeptide substrates.
AB - Most, if not all, of the cellular functions of Hsp70 proteins require the
assistance of a DnaJ homologue, which accelerates the weak intrinsic ATPase
activity of Hsp70 and serves as a specificity factor by binding and targeting
specific polypeptide substrates for Hsp70 action. We have used pre-steady-state
kinetics to investigate the interaction of the Escherichia coli DnaJ and DnaK
proteins, and the effects of DnaJ on the ATPase reaction of DnaK. DnaJ
accelerates hydrolysis of ATP by DnaK to such an extent that ATP binding by DnaK
becomes rate-limiting for hydrolysis. At high concentrations of DnaK under single
turnover conditions, the rate-limiting step is a first-order process, apparently
a change of DnaK conformation, that accompanies ATP binding and proceeds at 12-15
min-1 at 25 degrees C and 1-1.5 min-1 at 5 degrees C. By prebinding ATP to DnaK
and subsequently adding DnaJ, the effects of this slow step may be bypassed, and
the maximal rate-enhancement of DnaJ on the hydrolysis step is approximately 15
000-fold at 5 degrees C. The interaction of DnaJ with DnaK.ATP is likely a rapid
equilibrium relative to ATP hydrolysis, and is relatively weak, with a KD of
approximately 20 microM at 5 degrees C, and weaker still at 25 degrees C. In the
presence of saturating DnaJ, the maximal rate of ATP hydrolysis by DnaK is
similar to previously reported rates for peptide release from DnaK.ATP. This
suggests that when DnaK encounters a DnaJ-bound polypeptide or protein complex, a
significant fraction of such events result in ATP hydrolysis by DnaK and
concomitant capture of the polypeptide substrate in a tight complex with
DnaK.ADP. Furthermore, a broadly applicable kinetic mechanism for DnaJ-mediated
specificity of Hsp70 action arises from these observations, in which the
specificity arises largely from the acceleration of the hydrolysis step itself,
rather than by DnaJ-dependent modulation of the affinity of Hsp70 for substrate
polypeptides.
PMID- 10194334
TI - Time-resolved fluorescence anisotropy study of the refolding reaction of the
alpha-subunit of tryptophan synthase reveals nonmonotonic behavior of the
rotational correlation time.
AB - Time-resolved fluorescence anisotropy of a bound extrinsic probe was studied in
an effort to characterize dynamic properties of the transient partially folded
forms that appear during the folding of the alpha-subunit of tryptophan synthase
(alphaTS) from Escherichia coli. Previous studies have shown that alphaTS, a
single structural domain, can be cleaved into autonomously folding amino- and
carboxy-folding units comprising residues 1-188 and 189-268, respectively
[Higgins, W., Fairwell, T., and Miles, E. W. (1979) Biochemistry 18, 4827-4835].
By use of a double-kinetic approach [Jones, B. E., Beechem, J. M., and Matthews,
C. R. (1995) Biochemistry 34, 1867-1877], the rotational correlation time of 1
anilino-8-naphthalene sulfonate bound to nonpolar surfaces of folding
intermediates was measured by time-correlated single photon counting at varying
time delays following initiation of folding from the urea-denatured form by
stopped-flow techniques. Comparison of the rotational correlation times for the
full-length alphaTS and the amino-terminal fragment suggests that folding of the
amino-terminal fragment and carboxy-terminal fragment is coordinated, not
autonomous, on the milliseconds to seconds time scale. If a spherical shape is
assumed, the apparent hydrodynamic radius of alphaTS after 5 ms is 26.8 A. The
radius increases to 28.5 A by 1 s before decreasing to the radius for native
alphaTS, 24.7 A, on a longer time scale (>25 s). Viewed within the context of the
kinetic folding model of alphaTS [Bilsel, O., Zitzewitz, J. A., Bowers, K. E. ,
and Matthews, C. R. (1999) Biochemistry 38, 1018-1029], the initial collapse
reflects the formation of an off-pathway burst-phase intermediate in which at
least part of the carboxy folding unit interacts with the amino folding unit. The
subsequent increase in rotational correlation time corresponds to the formation
of an on-pathway intermediate that leads to the native conformation. The apparent
increase in the radius for the on-pathway intermediate may reflect a change in
the interaction of the two-folding units, thereby forming a direct precursor for
the alpha/beta barrel structure.
PMID- 10194335
TI - An EPR study of the dinuclear iron site in the soluble methane monooxygenase from
Methylococcus capsulatus (Bath) reduced by one electron at 77 K: the effects of
component interactions and the binding of small molecules to the diiron(III)
center.
AB - Reduction of the soluble methane monooxygenase hydroxylase (MMOH) from
Methylococcus capsulatus (Bath) in frozen 4:1 buffer/glycerol solutions at 77 K
by mobile electrons generated by gamma-irradiation produces an EPR-detectable,
mixed-valent Fe(II)Fe(III) center. At this temperature the conformation of the
enzyme remains essentially unaltered during reduction, so the mixed-valent EPR
spectra serve to probe the active site structure of the EPR-silent, diiron(III)
state. The EPR spectra of the cryoreduced samples reveal that the diiron(III)
cluster of the resting hydroxylase has at least two chemically distinct forms,
the structures of which differ from that of the equilibrium Fe(II)Fe(III) site.
Their relative populations depend on pH, the presence of component B, and
formation of the MMOH/MMOB complex by reoxidation of the reduced, diiron(II)
hydroxylase. The formation of complexes between MMOB, MMOR, and the oxidized
hydroxylase does not measurably affect the structure of the diiron(III) site.
Cryogenic reduction in combination with EPR spectroscopy has also provided
information about interaction of MMOH in the diiron(III) state with small
molecules. The diiron(III) center binds methanol and phenols, whereas DMSO and
methane have no measurable effect on the EPR properties of cryoreduced
hydroxylase. Addition of component B favors the binding of some exogenous
ligands, such as DMSO and glycerol, to the active site diiron(III) state and
markedly perturbs the structure of the diiron(III) cluster complexed with
methanol or phenol. The results reveal different reactivity of the Fe(III)Fe(III)
and Fe(II)Fe(III) redox states of MMOH toward exogenous ligands. Moreover, unlike
oxidized hydroxylase, the binding of exogenous ligands to the protein in the
mixed-valent state is allosterically inhibited by MMOB. The differential
reactivity of the hydroxylase in its diiron(III) and mixed-valent states toward
small molecules, as well as the structural basis for the regulatory effects of
component B, is interpreted in terms of a model involving carboxylate shifts of a
flexible glutamate ligand at the Fe(II)Fe(III) center.
PMID- 10194336
TI - Modulating electron density in the bound product, 4-hydroxybenzoyl-CoA, by
mutations in 4-chlorobenzoyl-CoA dehalogenase near the 4-hydroxy group.
AB - The enzyme 4-chlorobenzoyl-CoA dehalogenase hydrolyzes 4-chlorobenzoyl-CoA (4-CBA
CoA) to 4-hydroxybenzoyl-CoA (4-HBA-CoA). Biochemical and crystallographic
studies have identified a critical role for the dehalogenase residue Asp 145 in
close proximity to the ligand's 4-hydroxy group in the structure of the product
enzyme complex. In the present study the effects of site selective mutations at
Asp 145 on the product complex are explored by Raman spectroscopy. The spectral
signatures of the WT-product complex, the large red shift in lambdamax, and the
complete reorganization of the benzoyl ring modes in Raman data are absent for
the D145E complex. The major spectral perturbations in the WT complex are brought
about by strong electron "pull" at the benzoyl carbonyl and electron "push" by
the side chain of Asp 145 near the 4-OH group. Acting in concert, these factors
polarize the benzoyl's pi-electrons. Since the Raman data show that very strong
electron pull occurs at the benzoyl's carbonyl in the D145E complex, it is
apparent that the needed electron push near the benzoyl's 4-OH group is missing.
Thus, very precise positioning of Asp 145's side chain near the benzoyl's 4
position is needed to bring about the dramatic electron reorganization seen in
the WT complex, and this criterion cannot be met by the glutamate side chain with
its additional CH2 group. For two other Asp145 mutants D145A and D145S that lack
catalytic activity, Raman difference spectroscopic data for product complexes
demonstrate the presence of a population of ionized product (i.e., 4-O-) in the
active sites. The presence of the ionized phenolate form explains the observation
that these complexes have highly red-shifted absorbance maxima with lambdamaxs
near 400 nm. For the WT complex only the 4-OH form is seen, ionization being
energetically expensive with the presence of the proximal negative charge on the
Asp 145 side chain. Semiquantitative estimates of the pKa for the bound product
in D145S and D145A indicate that this ionization lies in the pH 6.5-7.0 range.
This is approximately 2 pH units below the pKa for the free product. The Raman
spectrum of 4-dimethylaminobenzoyl-CoA undergoes major changes upon binding to
dehalogenase. The bound form has two features near 1562 and 1529 cm-1 and
therefore closely resembles the spectrum of product bound to wild-type enzyme,
which underlines the quinonoid nature in these complexes. The use of a newly
developed Raman system allowed us to obtain normal (nonresonance) Raman data for
the dehalogenase complexes in the 100-300 microM range and heralds an important
advance in the application of Raman spectroscopy to dilute solutions of
macromolecules.
PMID- 10194337
TI - Product catalyzes the deamidation of D145N dehalogenase to produce the wild-type
enzyme.
AB - Aspartate 145 plays an essential role in the active site of 4-chlorobenzoyl-CoA
dehalogenase, forming a transient covalent link at the 4-position of the benzoate
during the conversion of the substrate to 4-hydroxybenzoyl-CoA. Replacement of
Asp 145 by residues such as alanine or serine results in total inactivation, and
stable complexes can be formed with either substrate or product. The Raman
spectroscopic characterization of some of the latter is described in the
preceding publication (Dong et al.). The present work investigates complexes
formed by D145N dehalogenase and substrate or product. Time-resolved absorption
and Raman difference spectroscopic data show that these systems evolve rapidly
with time. For the substrate complex, initially the absorption and Raman spectra
show the signatures of the substrate bound in the active site of the asparagine
145 form of the enzyme but these signatures are accompanied by those for the
ionized product. After several minutes these signatures disappear to be replaced
with those closely resembling the un-ionized product in the active site of wild
type dehalogenase. Similarly, for the product complex, the absorption and Raman
spectra initially show evidence for ionized product in the active site of D145N,
but these are rapidly replaced by signatures closely resembling the un-ionized
product bound to wild-type enzyme. It is proposed that product bound to the
active site of asparagine 145 dehalogenase catalyzes the deamidation of the
asparagine side chain to produce the wild-type aspartate 145. For the complexes
involving substrate, the asparagine 145 enzyme population contains a small amount
of the WT enzyme, formed by spontaneous deamidation, that produces product. In
turn, these product molecules catalyze the deamidation of Asn 145 in the major
enzyme population. Thus, conversions of substrate to product and of D145N to
D145D dehalogenase go on simultaneously. The spontaneous deamidation of
asparagine 145 has been characterized by allowing the enzyme to stand at RT in
Hepes buffer at pH 7.5. Under these conditions deamidation occurs with a rate
constant of 0.0024 h-1. The rate of product-catalyzed deamidation in Hepes buffer
at 22 degrees C was measured by stopped-flow kinetics to be 0.024 s-1, 36000
times faster than the spontaneous process. A feature near 1570 cm-1 could be
observed in the early Raman spectra of both substrate and product-enzyme
complexes. This band is not associated with either substrate or product and is
tentatively assigned to an ester-like species formed by the attack of the
product's 4-O- group on the carbonyl of asparagine's side chain and the
subsequent release of ammonia. A reaction scheme is proposed, incorporating these
observations.
PMID- 10194338
TI - Evidence for altered ion transport in Saccharomyces cerevisiae overexpressing
human MDR 1 protein.
AB - Recently [Hoffman, M. M., and Roepe, P. D. (1997) Biochemistry 36, 11153-11168]
we presented evidence for a novel Na+- and Cl--dependent H+ transport process in
LR73/hu MDR 1 CHO transfectants that likely explains pHi, volume, and membrane
potential changes in eukaryotic cells overexpressing the hu MDR 1 protein. To
further explore this process, we have overexpressed human MDR 1 protein in yeast
strain 9.3 following a combination of approaches used previously [Kuchler, K.,
and Thorner, J. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 2302-2306; Ruetz, S., et
al. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 11588-11592]. Thus, a truncated hu
MDR 1 cDNA was cloned behind a tandem array of sterile 6 (Ste6) and alchohol
dehydrogenase (Adh) promoters to create the yeast expression vector pFF1.
Valinomycin resistance of intact cells and Western blot analysis with purified
yeast plasma membranes confirmed the overexpression of full length, functional,
and properly localized hu MDR 1 protein in independently isolated 9.3/pFF1
colonies. Interestingly, relative valinomycin resistance and growth of the 9.3/hu
MDR 1 strains are found to strongly depend on the ionic composition of the growth
medium. Atomic absorption reveals significant differences in intracellular K+ for
9.3/hu MDR 1 versus control yeast. Transport assays using
[3H]tetraphenylphosphonium ([3H]TPP+) reveal perturbations in membrane potential
for 9.3/hu MDR 1 yeast that are stimulated by KCl and alkaline pHex. ATPase
activity of purified plasma membrane fractions from yeast strains and LR73/hu MDR
1 CHO transfectants constructed previously [Hoffman, M. M., et al. (1996) J. Gen.
Physiol. 108, 295-313] was compared. MDR 1 ATPase activity exhibits a higher pH
optimum and different salt dependencies, relative to yeast H+ ATPase. Inside-out
plasma membrane vesicles (ISOV) fabricated from 9.3/hu MDR 1 and control strains
were analyzed for formation of H+ gradients +/- verapamil. Similar pharmacologic
profiles are found for verapamil stimulation of MDR 1 ATPase activity and H+
pumping in 9.3/hu MDR 1 ISOV. In sum, these experiments strongly support the
notion that hu MDR 1 catalyzes H+ transport in some fashion and lowers membrane
potential in yeast when K+ contributes strongly to that potential. In the
accompanying paper [Santai, C. T., Fritz, F., and Roepe, P. D. (1999)
Biochemistry 38, XXXX-XXXX] the effects of ion gradients on H+ transport by hu
MDR 1 are examined.
PMID- 10194339
TI - Effects of ion gradients on H+ transport mediated by human MDR 1 protein.
AB - In the previous paper we presented a variety of data consistent with significant
perturbations in 9.3 yeast plasma membrane ion transport upon overexpression of
the hu MDR 1 protein. Thus, in this paper, we compare formation of DeltapH for
inside-out yeast plasma membrane vesicles (ISOV) prepared from control 9.3/pVT
versus 9.3/hu MDR 1 yeast. Since MDR 1 ATPase activity has a broader, more
alkaline pH profile relative to endogenous yeast H+ ATPase activity, we analyzed
H+ pumping at pH >/= 8.0 in detail in order to selectively amplify hu MDR 1
contributions to H+ movement over those of the endogenous yeast H+ ATPase. We
observed: (1) imposition of a Cl- gradient oriented outside to in enhances
acidification for 9.3/pVT ISOV (as expected), but decreases acidification for
9.3/hu MDR 1 ISOV; (2) imposition of a Cl- gradient oriented inside to out
decreases acidification for 9.3/pVT ISOV (as expected) but enhances acidification
for 9.3/hu MDR 1 ISOV; (3) a Na+ gradient oriented in the same direction as the
Cl- gradient amplifies the effects due to hu MDR 1 when both gradients are
oriented inside to out, but not outside to in. The data are most easily explained
by interesting Na+, Cl-, and ATP-dependent H+ transport mediated by hu MDR 1
protein as previously suggested [Hoffman and Roepe (1997) Biochemistry 36, 11153
11168]. These data may help to resolve a variety of conflicting reports in the
literature regarding ion transport mediated by hu MDR 1 and have implications for
the physiology of a number of polarized epithelia in which hu MDR 1 is
endogenously expressed.
PMID- 10194340
TI - Characterizing the response of calcium signal transducers to generated calcium
transients.
AB - Cellular Ca2+ transients and Ca2+-binding proteins regulate physiological
phenomena as diverse as muscle contraction, neurosecretion, and cell division.
When Ca2+ is rapidly mixed with slow Ca2+ chelators, EGTA, or Mg2+/EDTA,
artificial Ca2+ transients (ACTs) of varying duration (0.1-50 ms half-widths
(hws)) and amplitude can be generated. We have exposed several Ca2+ indicators,
Ca2+-binding proteins, and a Ca2+-dependent enzyme to ACTs of various durations
and observed their transient binding of Ca2+, complex formation, and/or
activation. A 0.1 ms hw ACT transiently occupied approximately 70% of the N
terminal regulatory sites of troponin C consistent with their rapid Ca2+ on-rate
(8.7 +/- 2.0 x 10(7) M-1 s-1). A 1.1 ms hw ACT produced approximately 90%
transient binding of the N-terminal of calmodulin (CaM) to the RS-20 peptide, but
little binding of CaM's C-terminal to RS-20. A 0.6 ms hw ACT was sufficient for
the N-terminal of CaM to transiently bind approximately 60% of myosin light chain
kinase (MLCK), while a 1.8 ms hw ACT produced approximately 22% transient
activation of the sarcoplasmic reticulum (SR) Ca2+/ATPase. In both cases, the ACT
had fallen back to baseline approximately 10-30 ms before maximal binding of CaM
to MLCK or SR Ca2+/ATPase activation occurred and binding and enzyme activation
persisted long after the Ca transient had subsided. The use of ACTs has allowed
us to visualize how the Ca2+-exchange rates of Ca2+-binding proteins dictate
their Ca2+-induced conformational changes, Ca2+-induced protein/peptide and
protein/protein interactions, and enzyme activation and inactivation, in response
to Ca2+ transients of various amplitude and duration. By characterizing the
response of these proteins to ACTs, we can predict with greater certainty how
they would respond to natural Ca2+ transients to regulate cellular phenomena.
PMID- 10194341
TI - Regulation of caspase activation and cis-diamminedichloroplatinum(II)-induced
cell death by protein kinase C.
AB - Activation of caspases is critical for the induction of apoptosis. We have shown
previously that cell death mediated by the anticancer agent cis
diamminedichloroplatinum(II) (cDDP) is influenced by the protein kinase C (PKC)
signal transduction pathway. In the present study, we have examined whether
regulation of cDDP sensitivity by PKC involves caspase activation. cDDP caused a
time- and concentration-dependent increase in the generation of the catalytic
fragment (CF) of novel (n) PKCdelta, nPKCepsilon, and atypical (a) PKCzeta but
had little effect on conventional (c) PKCalpha. Cleavage of PKC isozymes was
associated with the activation of caspase-3 and -7 but not of caspase-2. PKC
activators enhanced cDDP-induced cleavage of these isozymes and activation of
caspase-3. Rottlerin, an inhibitor of nPKCdelta, blocked caspase-3 activation and
proteolytic cleavage of nPKCdelta by cDDP. Bryostatin 1, which elicits a biphasic
concentration-response in potentiating cell death by cDDP, exhibited a similar
biphasic effect on cDDP-induced activation of caspase-3 and caspase-7 and the
cleavage of poly(ADP-ribose) polymerase; while 1 nM bryostatin 1 induced maximum
activation of these caspases, 1 microM bryostatin 1 had little effect. z-DEVD
fmk, an inhibitor of caspase-3-like proteases, prevented cDDP-induced cell death.
Bryostatin 1 also induced a similar biphasic down-regulation of nPKCdelta but not
of cPKCalpha or nPKCepsilon. These results suggest that nPKCdelta not only acts
downstream of caspases but also regulates the activation of caspases and that the
biphasic concentration response of bryostatin 1 on cDDP-induced cell death could
be explained by its distinct effect on nPKCdelta down-regulation and caspase
activation.
PMID- 10194342
TI - Unexpected divergence of enzyme function and sequence: "N-acylamino acid
racemase" is o-succinylbenzoate synthase.
AB - A protein identified as "N-acylamino acid racemase" from Amycolaptosis sp. is an
inefficient enzyme (kcat/Km = 3.7 x 10(2) M-1 s-1). Its sequence is 43% identical
to that of an unidentified protein encoded by the Bacillus subtilis genome. Both
proteins efficiently catalyze the o-succinylbenzoate synthase reaction in
menaquinone biosynthesis (kcat/Km = 2.5 x 10(5) and 7.5 x 10(5) M-1 s-1,
respectively), suggesting that this is their "correct" metabolic function. Their
membership in the mechanistically diverse enolase superfamily provides an
explanation for the catalytic promiscuity of the protein from Amycolaptosis. The
adventitious promiscuity may provide an example of a protein poised for evolution
of a new enzymatic function in the enolase superfamily. This study demonstrates
that the correct assignment of function to new proteins in functional and
structural genomics may require an understanding of the metabolism of the
organism.
PMID- 10194343
TI - Mapping protein-protein interactions with a library of tethered cutting reagents:
the binding site of sigma 70 on Escherichia coli RNA polymerase.
AB - Surface-exposed lysine amino groups and other reactive nucleophiles of the sigma
70 protein were conjugated with the cutting reagent iron (S)-1-[p
(bromoacetamido)benzyl]ethylenediaminetetraacetate (FeBABE) via 2-iminothiolane
(2IT) with low efficiency. The result is a library of sigma 70 conjugates, with
an average of 1-2 cutting reagents tethered to any of a variety of sites (lysine,
cysteine, etc.) on the surface of the protein. Model calculations indicate that
the conjugates in this library should be capable of cutting nearby sites on the
backbone of almost any protein or nucleic acid to which sigma 70 binds. Since
cutting occurs only when the protein is bound, the cleaved sites indicate
proximity; since only proximal sites are cleaved, interpretation of the results
is straightforward. We used this library to map the periphery of the binding site
on the core enzyme (alpha 2 beta beta') of Escherichia coli RNA polymerase. The
beta subunit was cut primarily within its conserved regions C, D, Rif I, and G;
additional sites were also cut between A and B and near conserved regions E and
H. The cut sites within the beta' subunit were intensely clustered between
residues 250-450, which include its conserved regions C and D, along with two
additional cut sites in conserved regions A and G. No cut sites on the alpha
subunit were observed. These results recapitulate and extend those obtained using
FeBABE conjugates of seven strategically placed single-Cys sigma 70 mutants
[Owens, J. T., Miyake, R., Murakami, K., Chmura, A. J., Fujita, N., Ishihama, A.,
and Meares, C. F. (1998) Proc. Natl. Acad. Sci. U.S.A. 95, 6021-6026]. This
technique provides a straightforward, general approach to mapping protein
interactions without mutagenesis.
PMID- 10194344
TI - X-ray structure of 5-aminolevulinic acid dehydratase from Escherichia coli
complexed with the inhibitor levulinic acid at 2.0 A resolution.
AB - 5-Aminolevulinic acid dehydratase (ALAD), an early enzyme of the tetrapyrrole
biosynthesis pathway, catalyzes the dimerization of 5-aminolevulinic acid to form
the pyrrole, porphobilinogen. ALAD from Escherichia coli is shown to form a homo
octameric structure with 422 symmetry in which each subunit adopts the TIM barrel
fold with a 30-residue N-terminal arm. Pairs of monomers associate with their
arms wrapped around each other. Four of these dimers interact, principally via
their arm regions, to form octamers in which each active site is located on the
surface. The active site contains two lysine residues (195 and 247), one of which
(Lys 247) forms a Schiff base link with the bound substrate analogue, levulinic
acid. Of the two substrate binding sites (referred to as A and P), our analysis
defines the residues forming the P-site, which is where the first ALA molecule to
associate with the enzyme binds. The carboxyl group of the levulinic acid moiety
forms hydrogen bonds with the side chains of Ser 273 and Tyr 312. In proximity to
the levulinic acid is a zinc binding site formed by three cysteines (Cys 120,
122, and 130) and a solvent molecule. We infer that the second substrate binding
site (or A-site) is located between the triple-cysteine zinc site and the bound
levulinic acid moiety. Two invariant arginine residues in a loop covering the
active site (Arg 205 and Arg 216) appear to be appropriately placed to bind the
carboxylate of the A-site substrate. Another metal binding site, close to the
active site flap, in which a putative zinc ion is coordinated by a carboxyl and
five solvent molecules may account for the activating properties of magnesium
ions.
PMID- 10194345
TI - Crystal structure determination of cholesterol oxidase from Streptomyces and
structural characterization of key active site mutants.
AB - Cholesterol oxidase is a monomeric flavoenzyme which catalyzes the oxidation and
isomerization of cholesterol to cholest-4-en-3-one. The enzyme interacts with
lipid bilayers in order to bind its steroid substrate. The X-ray structure of the
enzyme from Brevibacterium sterolicum revealed two loops, comprising residues 78
87 and residues 433-436, which act as a lid over the active site and facilitate
binding of the substrate [Vrielink et al. (1991) J. Mol. Biol. 219, 533-554; Li
et al. (1993) Biochemistry 32, 11507-11515]. It was postulated that these loops
must open, forming a hydrophobic channel between the membrane and the active site
of the protein and thus sequestering the cholesterol substrate from the aqueous
environment. Here we describe the three-dimensional structure of the homologous
enzyme from Streptomyces refined to 1.5 A resolution. Structural comparisons to
the enzyme from B. sterolicum reveal significant conformational differences in
these loop regions; in particular, a region of the loop comprising residues 78-87
adopts a small amphipathic helical turn with hydrophobic residues directed toward
the active site cavity and hydrophilic residues directed toward the external
surface of the molecule. It seems reasonable that this increased rigidity reduces
the entropy loss that occurs upon binding substrate. Consequently, the
Streptomyces enzyme is a more efficient catalyst. In addition, we have determined
the structures of three active site mutants which have significantly reduced
activity for either the oxidation (His447Asn and His447Gln) or the isomerization
(Glu361Gln). Our structural and kinetic data indicate that His447 and Glu361 act
as general base catalysts in association with conserved water H2O541 and Asn485.
The His447, Glu361, H2O541, and Asn485 hydrogen bond network is conserved among
other oxidoreductases. This catalytic tetrad appears to be a structural motif
that occurs in flavoenzymes that catalyze the oxidation of unactivated alcohols.
PMID- 10194346
TI - Design and synthesis of substrate analogue inhibitors of peptide deformylase.
AB - Series of substrates derivatives of peptide deformylase were systematically
synthesized and studied for their capacities to undergo hydrolysis. Data analysis
indicated the requirement for a hydrophobic first side chain and for at least two
main chain carbonyl groups in the substrate. For instance, Fo-Met-OCH3 and Fo-Nle
OCH3 were the minimal substrates of peptide deformylase obtained in this study,
while positively charged Fo-Nle-ArgNH2 was the most efficient substrate (kcat/Km
= 4.5 x 10(5) M-1.s-1). On the basis of this knowledge, 3-mercapto-2
benzylpropanoylglycine (thiorphan), a known inhibitor of thermolysin, could be
predicted and further shown to inhibit the deformylation reaction. The inhibition
by this compound was competitive and proved to depend on the hydrophobicity at
the P1' position. Spectroscopic evidence that the sulfur group of thiorphan binds
next to the active site metal ion on the enzyme could be obtained. Consequently,
a small thiopseudopeptide derived from Fo-Nle-OCH3 was designed and synthesized.
This compound behaved as a competitive inhibitor of peptide deformylase with KI =
52 +/- 5 microM. Introduction of a positive charge to this thiopeptide via
addition of an arginine at P2' improved the inhibition constant up to 2.5 +/- 0.5
microM, a value 4 orders of magnitude smaller than that of the starting
inhibitors. Evidence that this inhibitor, imino[(5-methoxy-5-oxo-4-[[2
(sulfanylmethyl)hexanoyl]amino]pentyl )am ino]methanamine, binds inside the
active site cavity of peptide deformylase, while keeping intact the 3D fold of
the protein, was provided by NMR. A fingerprint of the interaction of the
inhibitor with the residues of the enzyme was obtained.
PMID- 10194347
TI - The staphylococcal alpha-toxin pore has a flexible conformation.
AB - The alpha-toxin from Staphylococcus aureus undergoes several conformational
changes from the time it is released from the bacterium to the moment it forms a
channel in the plasma membrane of its target cell. It is initially a soluble
monomer, which undergoes membrane binding and oligomerization into a heptameric
ring and finally inserts into the lipid bilayer to form a pore. Here we have
analyzed the stability of different forms of the alpha-toxin (monomer as well as
heptamers in solution, bound to the membrane and membrane-inserted) by
differential scanning calorimetry and limited proteolysis. Data presented here
show that, in contrast to both the membrane-bound prepore complex and the monomer
in solution, the membrane-inserted alpha-toxin channel does not undergo
cooperative unfolding and is highly susceptible to proteases. These observations
suggest that the channel has a looser conformation. Interestingly, resistance to
proteases could be recovered upon solubilization of the channel, indicating that
the loss of rigid tertiary packing only occurred upon membrane insertion. Far-UV
CD data, however, suggest that the transmembrane beta-barrel must be stably
folded and that therefore only the Cap and Rim domains of the channel are loosely
packed. All together, our data show that the alpha-toxin channel is not a rigid
complex within the membrane but adopts a rather flexible conformation.
PMID- 10194348
TI - Ligand-induced conformational changes in the crystal structures of Pneumocystis
carinii dihydrofolate reductase complexes with folate and NADP+.
AB - Structural data from two independent crystal forms (P212121 and P21) of the
folate (FA) binary complex and from the ternary complex with the oxidized
coenzyme, NADP+, and recombinant Pneumocystis carinii dihydrofolate reductase
(pcDHFR) refined to an average of 2.15 A resolution, show the first evidence of
ligand-induced conformational changes in the structure of pcDHFR. These data are
also compared with the crystal structure of the ternary complex of methotrexate
(MTX) with NADPH and pcDHFR in the monoclinic lattice with data to 2.5 A
resolution. Comparison of the data for the FA binary complex of pcDHFR with those
for the ternary structures reveals significant differences, with a >7 A movement
of the loop region near residue 23 that results in a new "flap-open" position for
the binary complex, and a "closed" position in the ternary complexes, similar to
that reported for Escherichia coli (ec) DHFR complexes. In the orthorhombic
lattice for the binary FA pcDHFR complex, there is also an unwinding of a short
helical region near residue 47 that places hydrophobic residues Phe-46 and Phe-49
toward the outer surface, a conformation that is stabilized by intermolecular
packing contacts. The pyrophosphate moiety of NADP+ in the ternary folate pcDHFR
complexes shows significant differences in conformation compared with that
observed in the MTX-NADPH-pcDHFR ternary complex. Additionally, comparison of the
conformations among these four pcDHFR structures reveals evidence for subdomain
movement that correlates with cofactor binding states. The larger binding site
access in the new "flap-open" loop 23 conformation of the binary FA complex is
consistent with the rapid release of cofactor from the product complex during
catalysis as well as the more rapid release of substrate product from the binary
complex as a result of the weaker contacts of the closed loop 23 conformation,
compared to ecDHFR.
PMID- 10194349
TI - Identification of residues of Escherichia coli phosphofructokinase that
contribute to nucleotide binding and specificity.
AB - The apparent affinity of phosphofructo-1-kinase (PFK) of Escherichia coli for ATP
is at least 10 times higher than for other nucleotides. Mutagenesis was directed
toward five residues that may interact with ATP: Y41, F76, R77, R82, and R111.
Alanine at position 41 or 76 increased the apparent Km by 49- and 62-fold,
respectively. Position 41 requires the presence of a large hydrophobic residue
and is not restricted to aromatic rings. Tryptophan and, to a lesser extent,
phenylalanine could substitute at position 76. None of the mutants at 41 or 76
showed a change in the preference for alternative purines, although F76W used CTP
3 times better than the wild type enzyme. Mutations of R77 suggested that the
interaction was hydrophobic with no influence on nucleotide preference. Mutation
of R82 to alanine or glutamic acid increased the apparent Km for ATP by more than
20-fold and lowered the kcat/Km with ATP more than 30-fold. However, these
mutants had a higher kcat/Km than wild type for both GTP and CTP, reflecting a
loss of substrate preference. A loss in preference is seen as well with R111A
where the kcat/Km for ATP decreases by only 68%, but the kcat/Km with GTP
increases more than 10-fold. Activities with ITP, CTP, and UTP are also higher
than with the wild type enzyme. Arginine residues at positions 82 and 111 are
important dictators of nucleoside triphosphate preference.
PMID- 10194350
TI - Structural basis for light activation of a chloroplast enzyme: the structure of
sorghum NADP-malate dehydrogenase in its oxidized form.
AB - Some key chloroplast enzymes are activated by light via a ferredoxin-thioredoxin
reduction system which reduces disulfide bridges in the enzymes. We describe for
the first time the structural basis for the redox activation of a chloroplast
enzyme, the NADP-dependent malate dehydrogenase (MDH) from Sorghum vulgare whose
structure has been determined and refined at 2.4 A resolution. In addition to the
normal structural components of MDHs, the enzyme exhibits extensions at both the
N- and C-termini, each of which contains a regulatory disulfide bridge which must
be reduced for activation. The N-terminal disulfide motif is inserted in a cleft
between the two subunits of the dimer, thereby locking the domains in each
subunit. The C-terminal disulfide keeps the C-terminal residues tight to the
enzyme surface and blocks access to the active site. Reduction of the N-terminal
disulfide would release the stopper between the domains and give the enzyme the
necessary flexibility. Simultaneous reduction of the C-terminal disulfide would
free the C-terminal residues from binding to the enzyme and make the active site
accessible.
PMID- 10194351
TI - Amphipathic alpha-helix bundle organization of lipid-free chicken apolipoprotein
A-I.
AB - Apolipoprotein A-I (apoA-I), the major protein component of plasma high-density
lipoprotein (HDL), exists in alternate lipid-free and lipid-bound states. Among
various species, chicken apoA-I possesses unique structural properties: it is a
monomer in the lipid-free state and it is virtually the sole protein component of
HDL. Near-UV circular dichroism (CD) spectroscopic studies provide evidence that
chicken apoA-I undergoes a major conformational change upon binding to lipid,
while far-UV CD data indicate its overall alpha-helix content is maintained
during this transition. The fluorescence emission wavelength maximum (excitation
295 nm) of the tryptophans in apoA-I (W74 and W107) displayed a marked blue shift
in both the lipid-free (331 nm) and HDL-bound (329 nm) states, compared to free
tryptophan in solution. The effect of aqueous quenchers on tryptophan
fluorescence was determined in lipid-free, dimyristoylphosphatidylcholine (DMPC)-
and HDL-bound states. The most effective quencher in the lipid-free and HDL-bound
states was acrylamide, giving rise to Ksv values of 1.6 +/- 0.1 and 1.2 +/- 0.1 M
1, respectively. Together, these data suggest that a hydrophobic environment
around the two tryptophan residues (W74 and W107) is maintained in alternate
conformations of the protein. To further probe the molecular organization of
lipid-free apoA-I, its effect on the fluorescence properties of 8-anilino-1
naphthalenesulfonic acid (ANS) was determined. Human and chicken apoA-I induced a
similar increase in ANS fluorescence quantum yield, in keeping with the
hypothesis that these proteins adopt a similar global fold in the absence of
lipid. When considered with near- and far-UV CD experiments, the data support a
model in which lipid-free chicken apoA-I is organized as an amphipathic alpha
helix bundle. In other studies, lipid-soluble quenchers, 5-, 7-, 10-, and 12
DOXYL stearic acid (DSA), were employed to investigate the depth of penetration
of apoA-I into the surface monolayer of spherical HDL particles. 5-DSA was the
most effective quencher, suggesting that apoA-I tryptophan residues localize near
the surface monolayer, providing a structural rationale for the reversibility of
apoA-I-lipoprotein particle interactions.
PMID- 10194352
TI - Functional analysis of the two zinc fingers of SRE, a GATA-type factor that
negatively regulates siderophore synthesis in Neurospora crassa.
AB - Multiple GATA factors, zinc finger DNA binding proteins that recognize consensus
GATA elements, exist in Neurospora crassa. One of them, SRE, is involved in
controlling the iron metabolic pathway of N. crassa. In N. crassa, iron transport
is mediated by a number of small cyclic peptides, known as siderophores. The
siderophore synthesis pathway is negatively regulated by SRE; a loss-of-function
sre mutant strain showed partial constitutive synthesis of siderophore. In the
research presented here, the negative function of SRE was further confirmed by a
heterokaryon test and by gene complementation. SRE was expressed as a GST fusion
protein. In vitro EMSA revealed that SRE binds specifically to DNA molecules
containing GATA sequence elements. Autoregulation of sre gene expression appears
possible because the sre gene promoter itself contains GATA sequences. Mutations
were introduced into sre that lead to amino acid substitutions in each of the
zinc fingers that will disrupt their function. In vitro EMSA revealed that both N
terminal and C-terminal zinc fingers of SRE are involved in DNA binding. This
feature is different from that found with the vertebrate two zinc finger GATA
factors. Invivo tests, accomplished by transforming the mutant sre genes into sre
rip mutant, showed that SRE with mutations in either or both zinc fingers still
maintained its function under low-iron conditions. In contrast, these mutant SRE
proteins fail to function under high-iron conditions. Our results predict the
presence of other positive or negative regulators of the siderophore synthetic
pathway.
PMID- 10194353
TI - Mechanistic studies on the base-catalyzed transformation of neocarzinostatin
chromophore: roles of bulged DNA.
AB - Nucleic acid bulges have been implicated in a number of biological processes and
are specific cleavage targets for the enediyne antitumor antibiotic
neocarzinostatin chromophore (NCS-chrom) in a base-catalyzed, radical-mediated
reaction. Studies designed to elucidate the detailed mechanism of the base
catalyzed activation of NCS-chrom and to evaluate the roles of bulged DNA in its
activation are described. They show that nucleobases in the DNA bulge are not
required to form an effective bulge pocket but enhance the binding of the wedge
shaped activated drug molecule. Analysis of solvent deuterium isotope effects on
NCS-chrom degradation and DNA cleavage efficiency experiments suggests that the
spirolactone biradical 6 is a relatively stable species and that intramolecular
quenching of the C2 radical of 6 to form the biologically active
cyclospirolactone radical 7a occurs first (pathway a in Scheme 2), leaving the C6
radical to abstract the hydrogen atom from the DNA deoxyribose and to form the
cyclospirolactone 8. Binding of the activated drug at the bulge site is required,
but not sufficient, for efficient 8 formation, whereas cleavage of bulged DNA is
not essential. Efficient generation of 8, but inefficient DNA damage generation,
comes mainly from the likely high off-rate of 7a binding. The finding that
thymidine 5'-carboxylic acid-ended oligonucleotide fragment can be formed in the
reaction suggests that the process of DNA cleavage is rather slow and that
sequential oxidations of the target 5'-carbon are possible. Study of the effect
of solvent (methanol) concentration on NCS-chrom degradation indicates that
bulged DNA acts to assist the intramolecular quenching of the radical at C2 by
C8' ' of the naphthoate moiety by excluding solvent from the binding pocket, thus
preventing the formation of spirolactones 9, and by blocking radical
polymerization. Because in the absence or near absence of solvent methanol 8
formation does not reach even 10% that formed in the presence of bulged DNA, it
is possible that the DNA bulge also induces a conformational change in the drug
to promote the intramolecular reaction.
PMID- 10194354
TI - Determinants of DNA quadruplex structural type: sequence and potassium binding.
AB - There are DNA sequences which adopt the same quadruplex structural type in the
presence of sodium as in the presence of sodium and potassium. There are also
sequences that appear to have a requirement for the presence of potassium for the
adoption of a particular quadruplex structural type. Information about the basis
for these potassium effects has been obtained by examining the structures of a
set of DNAs with differing numbers of loop residues and different lengths of runs
of dG residues in the presence of sodium alone and in the presence of potassium
and sodium. On the basis of the results, obtained primarily via solution-state
NMR, it appears that very small loops favor parallel stranded quartet structures
which do not require the presence of potassium. DNAs with loops of two to four
residues and runs of two dG residues can form quadruplex structures of the "edge"
or "chair" type in the presence of potassium but not in the presence of sodium
alone. When all of the loops contain four residues, a "crossover" or "basket"
type structure can be formed in the presence of sodium as well as in the presence
of sodium and potassium. Structures with runs of three or four dG residues and
with loops from two to four residues can form basket or crossover type structures
in the absence of potassium. The presence of a purine in a loop can block both
potassium binding and formation of chair type structures. Modeling of the
interactions of cations with these quadruplex structures indicates that the
potassium ions required for chair type structures interact with a terminal
quartet and residues in the adjacent loop.
PMID- 10194355
TI - Characterization of the neuronal targeting protein spinophilin and its
interactions with protein phosphatase-1.
AB - Protein phosphatase-1 (PP1) plays an important role in a variety of cellular
processes, including muscle contraction, cell-cycle progression, and
neurotransmission. The localization and substrate specificity of PP1 are
determined by a class of proteins known as targeting subunits. In the present
study, the interaction between PP1 and spinophilin, a neuronal protein that
targets PP1 to dendritic spines, has been characterized. Deletion analysis
revealed that a high-affinity binding domain is located within residues 417-494
of spinophilin. This domain contains a pentapeptide motif (R/K-R/K-V/I-X-F)
between amino acids 447 and 451 (R-K-I-H-F) that is conserved in other PP1
regulatory subunits. Mutation of phenylalanine-451 (F451A) or deletion of the
conserved motif abolished the ability of spinophilin to bind PP1, as observed by
coprecipitation, overlay, and competition binding assays. In addition, deletion
of regions 417-442 or 474-494, either singly or in combination, impaired the
ability of spinophilin to coprecipitate PP1. A comparison of the binding and
inhibitory properties of spinophilin peptides suggested that distinct subdomains
of spinophilin are responsible for binding and modulating PP1 activity.
Mutational analysis of the modulatory subdomain revealed that spinophilin
interacts with PP1 via a mechanism unlike those used by the cytosolic inhibitors
DARPP-32 (dopamine- and cAMP-regulated phosphoprotein, Mr 32 000) and inhibitor
1. Finally, characterization of the interactions between spinophilin and PP1 has
facilitated the design of peptide antagonists capable of disrupting spinophilin
PP1 interactions. These studies support the notion that spinophilin functions in
vivo as a neuronal PP1 targeting subunit by directing the enzyme to postsynaptic
densities and regulating its activity toward physiological substrates.
PMID- 10194356
TI - Role of the 20-hydroxyl group in camptothecin binding by the topoisomerase I-DNA
binary complex.
AB - Recent findings concerning the structure of the covalent binary complex formed by
DNA topisomerase I and its DNA substrate, as well as the nature of interactions
with inhibitors that bind reversibly to this binary complex, have led to two
proposed models for the binding of the prototype inhibitor camptothecin to the
DNA-topisomerase I binary complex. While these models differ in many regards,
they both suggest the involvement of the 20-OH group of camptothecin in a donor
hydrogen bond with an enzyme side chain functional group. Presently, five
analogues of camptothecin that differ only at C-20 have been evaluated for their
ability to bind to the topoisomerase I-DNA binary complex and thereby inhibit
enzyme function. Both 20-chloro- and 20-bromocamptothecin bound as well to the
enzyme-DNA binary complex as 20-aminoCPT despite the absence of a substituent at
C-20 capable of contributing a donor hydrogen bond.
PMID- 10194357
TI - Inhibition of topoisomerase II catalytic activity by two ruthenium compounds: a
ligand-dependent mode of action.
AB - The ability of two structurally different ruthenium complexes to interfere with
the catalytic activity of topoisomerase II was studied to elucidate their
molecular mechanism of action and relative antineoplastic activity. The first
complex, [RuCl2(C6H6)(dmso)], could completely inhibit DNA relaxation activity of
topoisomerase II and form a drug-induced cleavage complex. This strongly suggests
that the drug interferes with topoisomerase II activity by cleavage complex
formation. The bi-directional binding of [RuCl2(C6H6)(dmso)] to DNA and
topoisomerase II was verified by immunoprecipitation experiments which confirmed
the presence of DNA and ruthenium in the cleavage complex. The second complex,
Ruthenium Salicylaldoxime, could not inhibit topoisomerase II relaxation activity
appreciably and also could not induce cleavage complex formation, though its DNA
binding characteristics and antiproliferation activity were almost comparable to
those of [RuCl2(C6H6)(dmso)]. The results suggest that the difference in ligands
and their orientation around a metal atom may be responsible for topoisomerase II
poisoning by the first complex and not by the second. A probable mechanism is
proposed for [RuCl2(C6H6)(dmso)], where the ruthenium atom interacts with DNA and
ligands of the metal atom form cross-links with topoisomerase II. This may
facilitate the formation of a drug-induced cleavage complex.
PMID- 10194358
TI - The role of water in the catalytic efficiency of triosephosphate isomerase.
AB - The structural basis for the effect of the S96P mutation in chicken
triosephosphate isomerase (cTIM) has been analyzed using a combination of X-ray
crystallography and Fourier transform infrared spectroscopy. The X-ray structure
is that of the enzyme complexed with phosphoglycolohydroxamate (PGH), an
intermediate analogue, solved at a resolution of 1.9 A. The S96P mutation was
identified as a second-site reverent when catalytically crippled mutants, E165D
and H95N, were subjected to random mutagenesis. The presence of the second
mutation leads to enhanced activity over the single mutation. However, the effect
of the S96P mutation alone is to decrease the catalytic efficiency of the enzyme.
The crystal structures of the S96P double mutants show that this bulky proline
side chain alters the water structure within the active-site cavity (E165D; ref
1) and prevents nonproductive binding conformations of the substrate (H95N; ref
2). Comparison of the S96P single mutant structure with those of the wild-type
cTIM, those of the single mutants (E165D and H95N), and those of the double
mutants (E165D/S96P and H95N/S96P) begins to address the role of the conserved
serine residue at this position. The results indicate that the residue positions
the catalytic base E165 optimally for polarization of the substrate carbonyl,
thereby aiding in proton abstraction. In addition, this residue is involved in
positioning critical water molecules, thereby affecting the way in which water
structure influences activity.
PMID- 10194359
TI - Alpha-secondary tritium kinetic isotope effects indicate hydrogen tunneling and
coupled motion occur in the oxidation of L-malate by NAD-malic enzyme.
AB - The NAD-malic enzyme from Ascaris suum catalyzes the divalent metal ion-dependent
oxidative decarboxylation of L-malate to give pyruvate and CO2, with NAD+ as the
oxidant. Alpha-secondary tritium kinetic isotope effects were measured with NAD+
or APAD+ and L-malate-2-H(D) and several different divalent metal ions. The alpha
secondary tritium kinetic isotope effects are slightly higher than 1 with NAD+
and L-malate as substrates, much larger than the expected inverse isotope effect
for a hybridization change from sp2 to sp3. The alpha-secondary tritium kinetic
isotope effects are reduced to values near 1 with L-malate-2-D as the substrate,
regardless of the metal ion that is used. Data suggest the presence of quantum
mechanical tunneling and coupled motion in the malic enzyme reaction when NAD+
and malate are used as substrates. Isotope effects were also measured using the
D/T method with NAD+ and Mn2+ as the substrate pair. A Swain-Schaad exponent of
2.2 (less than the value of 3.26 expected for strictly semiclassical behavior) is
estimated, suggesting the presence of other slow steps along the reaction
pathway. With APAD+ and Mn2+ as the substrate pair, inverse alpha-secondary
tritium kinetic isotope effects are observed, and a Swain-Schaad exponent of 3.3
is estimated, consistent with rate-limiting hydride transfer and no quantum
mechanical tunneling or coupled motion. Data are discussed in terms of the malic
enzyme mechanism and the theory developed by Huskey for D/T isotope effects as an
indicator of tunneling [Huskey, W. P. (1991) J. Phys. Org. Chem. 4, 361-366].
PMID- 10194360
TI - Catalytic cycle of the phosphatidylcholine-preferring phospholipase C from
Bacillus cereus. Solvent viscosity, deuterium isotope effects, and proton
inventory studies.
AB - The phosphatidylcholine-preferring phospholipase C from Bacillus cereus (PLCBc)
is a 28.5 kDa enzyme with three zinc ions in its active site. Although much is
known about the roles that various PLCBc active site amino acids play in binding
and catalysis, there is little information about the rate-determining step of the
PLCBc-catalyzed hydrolysis of phospholipids and the catalytic cycle of the
enzyme. To gain insight into these aspects of the hydrolysis, solvent viscosity
variation experiments were conducted to determine whether an external step
(substrate binding or product release) or an internal step (hydrolysis) is rate
limiting. The data indicate that the PLCBc-catalyzed reaction is unaffected by
changes in solvent viscosity. This observation is inconsistent with the notion of
substrate binding or product release being rate-determining and supports the
hypothesis that a chemical step is rate-limiting. Furthermore, a deuterium
isotope effect of 1.9 and a linear proton inventory plot indicate one proton is
transferred in the rate-determining step. These data may be used to formulate a
comprehensive catalytic cycle that is for the first time based on experimental
evidence. In this mechanism, Asp55 of PLCBc activates an active site water
molecule for attack on the phosphodiester bond, the hydrolysis of which is rate
limiting. The phosphorylcholine product is the first to leave the active site,
followed by diacylglycerol.
PMID- 10194361
TI - Effects of mutations of the alpha His45 residue of Vibrio harveyi luciferase on
the yield and reactivity of the flavin peroxide intermediate.
AB - This work was undertaken to investigate the functional consequences of mutations
of the essential alpha His45 residue of Vibrio harveyi luciferase, especially
with respect to the yield and reactivity of the flavin 4a-hydroperoxide
intermediate II. A total of 14 luciferase variants, each with a different single
residue replacement for the alpha His45, were examined. These variants showed
changes, mostly slight, in their light decay rates of the nonturnover
luminescence reaction and in their Km values for decanal and reduced riboflavin
5'-phosphate (FMNH2). All alpha His45 mutants, however, showed markedly reduced
bioluminescence activities, the magnitude of the reduction ranging from about 300
fold to 6 orders of magnitude. Remarkably, a good correlation was obtained for
the wild-type luciferase, 12 alpha His45-mutated luciferases, and six additional
variants with mutations of other alpha-subunit histidine residues between the
degrees of luminescence activity reduction and the dark decay rates of
intermediate II. Such a correlation further indicates that the activation of the
O-O bond fission is an important function of the flavin 4a-hydroperoxide
intermediate II. Both alpha H45G and alpha H45W were found to bind near
stoichiometric amounts of FMNH2. Moreover, each variant catalyzed the oxidation
of bound FMNH2 by two mechanisms, with a minor pathway leading to the formation
of a luminescence-active intermediate II and a major dark pathway not involving
any detectable flavin 4a-hydroperoxide species. This latter pathway mimics that
in the normal catalysis by flavooxidases, and its elicitation in luciferase was
demonstrated for the first time by single-residue mutations.
PMID- 10194362
TI - Chemical mechanism of Haemophilus influenzae diaminopimelate epimerase.
AB - Seven unique enzymatic steps lead to the biosynthesis of L-lysine from L
aspartate semialdehyde and pyruvate in bacteria. The immediate precursor to L
lysine is D,L-diaminopimelate, a diamino acid which is incorporated into the
pentapeptide of the Gram-negative peptidoglycan moiety. D,L-Diaminopimelate is
generated from the corresponding L,L-isomer by the dapF-encoded epimerase.
Diaminopimelate epimerase is a representative of the pyridoxal phosphate
independent amino acid racemases, for which substantial evidence exists
supporting the role of two cysteine residues as the catalytic acid and base. The
pH dependencies of the maximum velocities in the L,L --> D,L and D,L --> L,L
direction depend on a single catalytic group exhibiting pK values of 7.0 and 6.1,
respectively, which must be unprotonated for activity. The pH dependencies of the
V/K values in both directions depend on the ionization of two groups, one
exhibiting a pK value of 6.7 which must be unprotonated and one exhibiting a pK
value of 8.5 which must be protonated. Primary kinetic isotope effects on V and
V/K are unequal, with D(V/K) being larger than DV in both the forward and reverse
directions. Solvent kinetic isotope effects in both directions are inverse on
V/K, but normal on V. Both of these isotopic observations support a model in
which proton isomerization after catalysis and substrate dissociation is
kinetically significant. A single solvent "overshoot" is observed when L, L
diaminopimelate is incubated with enzyme in D2O; however, an unprecedented double
overshoot is observed when D,L-diaminopimelate is incubated with enzyme in D2O. A
model has been developed which allows these two overshoots to be simulated. A
chemical mechanism is proposed invoking the function of two cysteine residues,
Cys73 and Cys217, observed in the recently determined three-dimensional structure
of this enzyme [Cirilli, M., et al. (1998) Biochemistry 37, 16452-16458], as the
acid and base in the mechanism.
PMID- 10194363
TI - Oxygen activation catalyzed by methane monooxygenase hydroxylase component:
proton delivery during the O-O bond cleavage steps.
AB - The effects of solvent pH and deuteration on the transient kinetics of the key
intermediates of the dioxygen activation process catalyzed by the soluble form of
methane monooxygenase (MMO) isolated from Methylosinus trichosporium OB3b have
been studied. MMO consists of hydroxylase (MMOH), reductase, and "B" (MMOB)
components. MMOH contains a carboxylate- and oxygen-bridged binuclear iron
cluster that catalyzes O2 activation and insertion chemistry. The diferrous MMOH
MMOB complex reacts with O2 to form a diferrous intermediate compound O (O) and
subsequently a diferric intermediate compound P (P), presumed to be a peroxy
adduct. The O decay reaction was found to be pH-independent within error at 4
degrees C (kobs = 22 +/- 2 s-1 at pH 7.7; kobs = 26 +/- 2 s-1 at pH 7.0). In
contrast, the P formation rate was found to decrease sharply with increasing pH
to near zero at pH 8.6; the observed rate constants fit to a single deprotonation
event with a pKa = 7.6 and a maximal formation rate at 4 degrees C of kP = 9.1 +/
0.9 s-1 achieved near pH 6.5. The formation of P was slower than the
disappearance of O, indicating that at least one other undetected intermediate
(P) must form in between. P decays spontaneously to the highly chromophoric
intermediate, compound Q (Q). The decay rate of P matched the formation rate of
Q, and both rates decreased sharply with increasing pH to near zero at pH 8.6;
the observed rate constants fit to a single deprotonation event with a pKa = 7.6
and a maximal formation rate at 4 degrees C of kQ = 2.6 +/- 0.1 s-1 achieved near
pH 6.5. No pH dependence was observed for the decay of Q. The formation and decay
rates of P and the formation rate of Q decreased linearly with mole fraction of
D2O in the reaction mixture. Kinetic solvent isotope effect values of kH/kD = 1.3
+/- 0.1 (P formation) and kH/kD = 1.4 +/- 0.1 (P decay and Q formation) were
observed at 5 degrees C. The linearity of the proton inventory plots suggests
that only a single proton is transferred in the transition state of the formation
reaction for each intermediate. If these protons are transferred to the bound
oxygen molecule, as formally required by the reaction stoichiometry, the data are
consistent with a model in which water is formed concurrently with the formation
of the reactive bis mu-oxo-binuclear Fe(IV) species, Q.
PMID- 10194364
TI - Acid-base catalysis in the chemical mechanism of inosine monophosphate
dehydrogenase.
AB - Inosine-5'-monophosphate dehydrogenase (IMPDH) catalyzes the K+-dependent
reaction IMP + NAD + H2O --> XMP + NADH + H+ which is the rate-limiting step in
guanine nucleotide biosynthesis. The catalytic mechanism of the human type-II
IMPDH isozyme has been studied by measurement of the pH dependencies of the
normal reaction, of the hydrolysis of 2-chloro-IMP (which yields XMP and Cl- in
the absence of NAD), and of inactivation by the affinity label 6-chloro-purine
ribotide (6-Cl-PRT). The pH dependence of the IMPDH reaction shows bell-shaped
profiles for kcat and the kcat/Km values for both IMP and NAD, illustrating the
involvement of both acidic and basic groups in catalysis. Half-maximal kcat
values occur at pH values of 7.2 and 9.8; similar pK values of 6.9 and 9.4 are
seen in the kcat/Km profile for NAD. The kcat/Km profile for IMP, which binds
first in the predominantly ordered kinetic mechanism, shows pK values of 8.1 and
7.3 for acidic and basic groups, respectively. None of the kinetic pK values
correspond to ionizations of the free substrates and thus reflect ionization of
the enzyme or enzyme-substrate complexes. The rate of inactivation by 6-Cl-PRT,
which modifies the active site sulfhydryl of cysteine-331, increases with pH; the
pK of 7.5 reflects the ionization of the sulfhydryl in the E.6-Cl-PRT complex.
The pKs of the acids observed in the IMPDH reaction likely also reflect
ionization of the cysteine-331 sulfhydryl which adds to C-2 of IMP prior to NAD
reduction. The kcat and kcat/Km values for hydrolysis of 2-Cl-IMP show a pK value
of 9.9 for a basic group, similar to that seen in the overall reaction, but do
not exhibit the ionization of an acidic group. Surprisingly, the rates of 2-Cl
IMP hydrolysis and of inactivation by 6-Cl-PRT are not stimulated by K+, in
contrast to the >100-fold K+ activation of the IMPDH reaction. Apparently the
enigmatic role of K+ lies in the NAD(H)-dependent segment of the IMPDH reaction.
To evaluate the importance of hydrogen bonding in substrate binding, several
deamino- and deoxy-analogues of IMP were tested as substrates and inhibitors.
Only 2'-deoxy-IMP was a substrate; the other compounds tested were competitive
inhibitors with Ki values at most 10-fold greater than the KD for IMP,
illustrating the greater importance of hydrogen-bonding interactions in the
chemistry of the IMPDH reaction than simply in nucleotide binding.
PMID- 10194365
TI - 5-lipoxygenase binds calcium.
AB - 5-Lipoxygenase (5LO) catalyzes the first two steps in the biosynthesis of
leukotrienes and lipoxins and has therefore become an important target for
pharmacological treatment of inflammatory disorders. Binding of calcium to 5LO
was shown using several different approaches. Human recombinant enzyme was
expressed in E. coli and purified. Association of Ca2+ to 5LO was demonstrated by
a calcium-induced mobility shift in gel electrophoresis, by calcium overlay, by
gel filtration in the presence of calcium, and by equilibrium dialysis. The two
latter methods also showed that calcium binds reversibly to 5LO. Equilibrium
dialysis gave a Kd close to 6 microM; the stoichiometry of maximum calcium
binding seemed to average around two Ca2+ per 5LO. Similar results were obtained
when 5LO was inactivated during equilibrium dialysis, indicating that the calcium
binding site(s) is (are) different from the active site. By Triton X-114
partitioning, it was confirmed that calcium increases the hydrophobicity of 5LO.
PMID- 10194366
TI - Site-directed mutants of charged residues in the active site of tyrosine
hydroxylase.
AB - The active site of tyrosine hydroxylase consists of a hydrophobic cleft with an
iron atom near the bottom. Within the cleft are several charged residues which
are conserved across the family of pterin-dependent hydroxylases. We have studied
four of these residues, glutamates 326 and 332, aspartate 328, and arginine 316
in tyrosine hydroxylase, by site-directed substitution with alternate amino acid
residues. Replacement of arginine 316 with lysine results in a protein with a
Ktyr value that is at least 400-fold greater and a V/Ktyr value that is 4000-fold
lower than those found in the wild-type enzyme; substitution with alanine,
serine, or glutamine yields insoluble enzyme. Arginine 316 is therefore critical
for the binding of tyrosine. Replacement of glutamate 326 with alanine has no
effect on the KM value for tyrosine and results in a 2-fold increase in the KM
value for tetrahydropterin. The Vmax for DOPA production is reduced 9-fold, and
the Vmax for dihydropterin formation is reduced 4-fold. These data suggest that
glutamate 326 is not directly involved in catalysis. Replacement of aspartate 328
with serine results in a 26-fold higher KM value for tyrosine, a 8-fold lower
Vmax for dihydropterin formation, and a 13-fold lower Vmax for DOPA formation.
These data suggest that aspartate 328 has a role in tyrosine binding. Replacement
of glutamate 332 with alanine results in a 10-fold higher KM value for 6
methyltetrahydropterin with no change in the KM value for tyrosine, a 125-fold
lower Vmax for DOPA formation, and an only 3.3-fold lower Vmax for
tetrahydropterin oxidation. These data suggest that glutamate 332 is required for
productive tetrahydropterin binding.
PMID- 10194367
TI - Folding-unfolding equilibrium and kinetics of equine beta-lactoglobulin:
equivalence between the equilibrium molten globule state and a burst-phase
folding intermediate.
AB - The denaturant-induced equilibrium unfolding transition of equine beta
lactoglobulin was investigated by ultraviolet absorption, fluorescence, and
circular dichroism (CD) spectra. An equilibrium intermediate populates at
moderate denaturant concentrations, and its CD spectrum is similar to that of the
molten globule state previously observed for this protein at acid pH [Ikeguchi,
M., Kato, S., Shimizu, A., and Sugai, S. (1997) Proteins: Struct., Funct., Genet.
27, 567-575]. The unfolding and refolding kinetics were also investigated by the
stopped-flow CD and fluorescence. A significant change in the CD intensity was
observed within the dead time of measurements (25 ms) when the refolding reaction
was initiated by diluting the urea-unfolded protein solution, indicating the
transient accumulation of the folding intermediate. The CD spectrum of this burst
phase intermediate agrees well with that of the molten globule state at acid pH.
The stability of the burst-phase intermediate was also estimated from the urea
concentration dependence of the burst-phase amplitude, and it shows a fair
agreement with that of the equilibrium intermediate. These results indicate that
the molten globule state of equine beta-lactoglobulin populates at moderate urea
concentration as well as at acid pH and it is equivalent with the kinetic folding
intermediate.
PMID- 10194368
TI - Thermal stability and mode of oligomerization of the tetrameric peanut
agglutinin: a differential scanning calorimetry study.
AB - Peanut agglutinin is a homotetrameric legume lectin. The crystal structure of
peanut agglutinin shows that the four subunits associate in an unusual manner,
giving rise to open quaternary structure [Banarjee, R., et al. (1994) Proc. Natl.
Acad. Sci. U.S.A. 91, 227-231]. The thermal unfolding of peanut agglutinin has
been characterized by differential scanning calorimetry and gel filtration to
elucidate its thermal stability and its mode of oligomerization. The unfolding
process is reversible and could be described by a three-state model with two
transitions occurring at around 331 and 336 K. For the tetramer, the ratio of
DeltaHc/DeltaHv for the first transition is close to 4 and for the second
transition is close to 0.25, suggesting that 4 and 0.25 cooperative unit(s) of
the tetramer are involved in the first and second transitions, respectively. The
agreement between the model-independent DeltaHv(S) determined from the values of
the temperatures of the peak maximum (Tp1) with the protein concentration with
the values of DeltaHv obtained from the fit of the data to the transition
confirms that the first peak is associated with the dissociation of peanut
agglutinin tetramers (A4) to "folded" monomers (4A), whereas the second peak
describes the unfolding (4U) of these monomers. The overall process for the
thermal unfolding of peanut agglutinin could therefore be summarized as A4 <==>
4A <==> 4U. Gel filtration studies confirm this process, as peanut agglutinin
elutes as a tetramer up to 50 degrees C, and at and above 56 degrees C (Tm of
first transition), it elutes at a position commensurate with that of the folded
monomer of peanut agglutinin. The unfolding behavior of peanut agglutinin in the
presence of saturating amounts of carbohydrate ligands is similar to that
observed for the unligated form. The temperature of maximal stability of the
peanut agglutinin tetramer at pH 7.4 is calculated to be around 33 degrees C with
a maximal free energy of stabilization of 8.70 kcal/mol. The results demonstrate
that unfolding of peanut agglutinin goes through two distinct phases with folded
monomer being the intermediate.
PMID- 10194369
TI - The roles of Glu-327 and His-446 in the bisphosphatase reaction of rat liver 6
phosphofructo-2-kinase/fructose-2,6-bisphosphatase probed by NMR spectroscopic
and mutational analyses of the enzyme in the transient phosphohistidine
intermediate complex.
AB - The bisphosphatase domain derived from the rat liver 6-phosphofructo-2
kinase/fructose-2,6-bisphosphatase was studied by 1H-13C HMQC NMR spectroscopy of
the histidine C2' and H2' nuclei. The bacterially expressed protein was
specifically labeled with 13C at the ring C2' position of the histidines. Each of
the seven histidine residues gave rise to a single cross-peak in the HMQC
spectra, and these were assigned by use of a series of histidine-to-alanine point
mutants. His-304, His-344, and His-469 exhibit 13C and 1H resonances that
titrated with pH, while the remaining histidine-associated resonances did not.
The 13C and 1H chemical shifts indicate that at neutral pH, His-304 and His-446
are deprotonated, while His-469 is protonated. The pKa of His-344 was determined
to be 7.04. The 13C chemical shifts suggest that the deprotonated His-258 exists
as the N1' tautomer, while His-392 and His-419 are protonated in the resting,
wild-type enzyme. Mutation of the remaining member of the catalytic triad, Glu
327, to alanine in the resting enzyme caused an upfield shift of 1.58 and 1.30
ppm in the 1H and 13C dimensions, respectively, and significant narrowing of the
His-258 cross-peak. Mutation of His-446 to alanine produced perturbations of the
His-258 cross-peak that were similar to those detected in the E327A mutant. The
His-392 resonances were also shifted by the E327A and H446A mutations. These
observations strongly suggest that residues His-258, Glu-327, His-392, and His
446 exist within a network of interacting residues that encompasses the catalytic
site of the bisphosphatase and includes specific contacts with the C-terminal
regulatory region of the enzyme. The specifically 13C-labeled bisphosphatase was
monitored during turnover by HMQC spectra acquired from the transient N3'
phosphohistidine intermediate complex in the wild-type enzyme, the E327A mutant,
and the H446A mutant. These complexes were formed during reaction with the
physiological substrate fructose-2, 6-bisphosphate. Upon formation of the
phosphohistidine at His-258, the 13C and 1H resonances of this residue were
shifted downfield by 1.7 and 0.31 ppm, respectively, in the wild-type enzyme. The
upfield shifts of the His-258 resonances in the E327A and H446A mutant resting
enzymes were reversed when the phosphohistidine was formed, generating spectra
very similar to that of the wild-type enzyme in the intermediate complex. In
contrast, the binding of fructose-6-phosphate, the reaction product, to the
resting enzyme did not promote significant changes in the histidine-associated
resonances in either the wild-type or the mutant enzymes. The interpretation of
these data within the context of the X-ray crystal structures of the enzyme is
used to define the role of Glu-327 in the catalytic mechanism of the
bisphosphatase and to identify His-446 as a putative link in the chain of
molecular events that results in activation of the bisphosphatase site by cAMP
dependent phosphorylation of the hepatic bifunctional enzyme.
PMID- 10194370
TI - Assignment of 15N chemical shifts and 15N relaxation measurements for oxidized
and reduced iso-1-cytochrome c.
AB - A protocol for complete isotopic labeling of iso-1-cytochrome c from the
eukaryote Saccharomyces cerevisiae is reported. Assignments are reported for the
vast majority of the 15N amide resonances in both oxidized and reduced states.
15N heteronuclear relaxation experiments were collected to study the picosecond
nanosecond backbone dynamics of this protein. Relaxation rates were computed and
fit to spectral density functions by a model-free analysis. Backbone amides in
the overlapping loop B/C region are the most flexible on the picosecond
nanosecond time scale in both forms of the protein. The results show that, on
average, the protein backbone is slightly more dynamic in the oxidized than the
reduced state, though not significantly so. Exchange terms, which suggest
significant motion on a time scale at least an order of magnitude slower than the
overall correlation time of 5.2 ns, were required for only two residues in the
reduced state and 27 residues in the oxidized state. When analyzed on a per
residue basis, the lower order parameters found in the oxidized state were
scattered throughout the protein, with a few continuous segments found in loop C
and the C-terminal helix, suggesting greater flexibility of these regions in the
oxidized state. The results provide dynamic interpretations for previously
presented structural and functional data, including redox-dependent changes that
occur in the protein. The way is now paved for extensive dynamic analysis of
variant cytochromes c.
PMID- 10194371
TI - Hydrogen exchange behavior of [U-15N]-labeled oxidized and reduced iso-1
cytochrome c.
AB - Heteronuclear NMR spectroscopy was used to measure the hydrogen-deuterium
exchange rates of backbone amide hydrogens in both oxidized and reduced [U
15N]iso-1-cytochrome c from the yeast Saccharomyces cerevisiae. The exchange data
confirm previously reported data [Marmorino et al. (1993) Protein Sci. 2, 1966
1974], resolve several inconsistencies, and provide more thorough coverage of
exchange rates throughout the cytochrome c protein in both oxidation states.
Combining the data previously collected on unlabeled C102T with the current data
collected on [U-15N]C102T, exchange rates for 53 protons in the oxidized state
and 52 protons in the reduced state can now be reported. Most significantly,
hydrogen exchange measurements on [U-15N]iso-1-cytochrome c allowed the
observation of exchange behavior of the secondary structures, such as large
loops, that are not extensively hydrogen-bonded. For the helices, the most slowly
exchanging protons are found in the middle of the helix, with more rapidly
exchanging protons at the helix ends. The observation for the Omega-loops in
cytochrome c is just the opposite. In the loops, the ends contain the most slowly
exchanging protons and the loop middles allow more rapid exchange. This is found
to be true in cytochrome c loops, even though the loop ends are not attached to
any regular secondary structures. Some of the exchange data are strikingly
inconsistent with data collected on the C102S variant at a different pH, which
suggests pH-dependent dynamic differences in the protein structure. This new
hydrogen exchange data for loop residues could have implications for the
substructure model of eukaryotic cytochrome c folding. Isotopic labeling of
variant forms of cytochrome c can now be used to answer many questions about the
structure and folding of this model protein.
PMID- 10194372
TI - Reactions of nitric oxide with the reduced non-heme diiron center of the soluble
methane monooxygenase hydroxylase.
AB - The soluble methane monooxygenase system from Methylococcus capsulatus (Bath)
catalyzes the oxidation of methane to methanol and water utilizing dioxygen at a
non-heme, carboxylate-bridged diiron center housed in the hydroxylase (H)
component. To probe the nature of the reductive activation of dioxygen in this
system, reactions of an analogous molecule, nitric oxide, with the diiron(II)
form of the enzyme (Hred) were investigated by both continuous and discontinuous
kinetics methodologies using optical, EPR, and Mossbauer spectroscopy. Reaction
of NO with Hred affords a dinitrosyl species, designated Hdinitrosyl, with
optical spectra (lambdamax = 450 and 620 nm) and Mossbauer parameters (delta =
0.72 mm/s, DeltaEQ = 1.55 mm/s) similar to those of synthetic dinitrosyl
analogues and of the dinitrosyl adduct of the reduced ribonucleotide reductase R2
(RNR-R2) protein. The Hdinitrosyl species models features of the Hperoxo
intermediate formed in the analogous dioxygen reaction. In the presence of
protein B, Hdinitrosyl builds up with approximately the same rate constant as
Hperoxo ( approximately 26 s-1) at 4 degrees C. In the absence of protein B, the
kinetics of Hdinitrosyl formation were best fit with a biphasic A --> B --> C
model, indicating the presence of an intermediate species between Hred and
Hdinitrosyl. This result contrasts with the reaction of Hred with dioxygen, in
which the Hperoxo intermediate forms in measurable quantities only in the
presence of protein B. These findings suggest that protein B may alter the
positioning but not the availability of coordination sites on iron for exogenous
ligand binding and reactivity.
PMID- 10194373
TI - The conformational and dynamic basis for ligand binding reactivity in hemoglobin
Ypsilanti (beta 99 asp-->Tyr): origin of the quaternary enhancement effect.
AB - Hemoglobin Ypsilanti (HbY) is a stable tetrameric hemoglobin that binds oxygen
with little or no cooperativity and with high affinity [Doyle, M. L., et al.
(1992) Proteins: Struct., Funct., Genet. 14, 351-362]. It displays an especially
large quaternary enhancement effect. An X-ray crystallographic study [Smith, F.
R., et al. (1991) Proteins: Struct., Funct., Genet. 10, 81-91] of the carboxy
derivative of this hemoglobin (COHbY) revealed a new quaternary structure that
partially resembles the recently described R2 structure [Silva, M. M., et al.
(1992) J. Biol. Chem. 267, 17248-17256]. Very little is known about either the
solution phase conformations of the liganded and deoxy forms of HbY or the
molecular basis for the large quaternary enhancement effect (Doyle et al., 1992).
In this study, near-IR absorption, Soret-enhanced Raman, and UV (229 nm)
resonance Raman spectroscopies are used to probe the liganded and deoxy
derivatives of HbY in solution. Nanosecond time-resolved near-IR absorption
measurements are used to expose the relaxation properties of the photoproduct of
COHbY. Time-resolved (Soret band) absorption is used to generate the geminate and
solvent phase ligand rebinding curves for photodissociated COHbY. The
spectroscopic results indicate that COHbY has an R-like conformation with respect
to both the proximal heme pocket and the hinge region of the alpha 1 beta 2
interface. The deoxy derivative of HbY has spectroscopic features that are very
similar to those observed for species assigned to the deoxy R or half-liganded R
conformations of human adult hemoglobin (HbA). The 10 ns to 100 micros relaxation
properties of the photoproduct of COHbY are distinctly different from those of
HbA in that for HbY, little if any tertiary or quaternary relaxation is observed.
The near-absence of relaxation in the HbY photoproduct explains the differences
in the geminate and solvent phase CO recombination between HbA and HbY. The
impact of the conformational and relaxation properties of HbY on the geminate
rebinding process forms the basis of a model that accounts for the large
quaternary enhancement effect reported for HbY (Doyle et al., 1992). In addition,
the spectroscopic data and the X-ray crystallographic results explain the slow
relaxation for HbY and the near-absence of cooperative ligand binding for this
protein based on the behavior of the penultimate tyrosines.
PMID- 10194374
TI - Cu XAS shows a change in the ligation of CuB upon reduction of cytochrome bo3
from Escherichia coli.
AB - Copper X-ray absorption spectroscopy (XAS) has been used to examine the
structures of the Cu(II) and Cu(I) forms of the cytochrome bo3 quinol oxidase
from Escherichia coli. Cytochrome bo3 is a member of the superfamily of heme
copper respiratory oxidases. Of particular interest is the fact that these
enzymes function as redox-linked proton pumps, resulting in the net translocation
of one H+ per electron across the membrane. The molecular mechanism of how this
pump operates and the manner by which it is linked to the oxygen chemistry at the
active site of the enzyme are unknown. Several proposals have featured changes in
the coordination of CuB during enzyme turnover that would result in sequential
protonation or deprotonation events that are key to the functioning proton pump.
This would imply lability of the ligands to CuB. In this work, the structure of
the protein in the immediate vicinity of CuB, in both the fully oxidized and
fully reduced forms of the enzyme, has been examined by Cu XAS, a technique that
is particularly sensitive to changes in metal coordination. The results show that
in the oxidized enzyme, CuB(II) is four-coordinate, consistent with three
imidazoles and one hydroxyl (or water). Upon reduction of the enzyme, the
coordination of CuB(I) is significantly altered, consistent with the loss of one
of the histidine imidazole ligands in at least a substantial fraction of the
population. These data add to the credibility that changes in the ligation of CuB
might occur during catalytic turnover of the enzyme and, therefore, could, in
principle, be part of the mechanism of proton pumping.
PMID- 10194375
TI - Low-frequency fourier transform infrared spectroscopy of the oxygen-evolving and
quinone acceptor complexes in photosystem II.
AB - The low-frequency (<1000 cm-1) region of the IR spectrum has the potential to
provide detailed structural and mechanistic insight into the photosystem
II/oxygen evolving complex (PSII/OEC). A cluster of four manganese ions forms the
core of the OEC and diagnostic manganese-ligand and manganese-substrate modes are
expected to occur in the 200-900 cm-1 range. However, water also absorbs IR
strongly in this region, which has limited previous Fourier transform infrared
(FTIR) spectroscopic studies of the OEC to higher frequencies (>1000 cm-1). We
have overcome the technical obstacles that have blocked FTIR access to low
frequency substrate, cofactor, and protein vibrational modes by using partially
dehydrated samples, appropriate window materials, a wide-range MCT detector, a
novel band-pass filter, and a closely regulated temperature control system. With
this design, we studied PSII/OEC samples that were prepared by brief illumination
of O2 evolving and Tris-washed preparations at 200 K or by a single saturating
laser flash applied to O2 evolving and inhibited samples at 250 K. These
protocols allowed us to isolate low-frequency modes that are specific to the QA
/QA and S2/S1 states. The high-frequency FTIR spectra recorded for these samples
and parallel EPR experiments confirmed the states accessed by the trapping
procedures we used. In the S2/S1 spectrum, we detect positive bands at 631 and
602 cm-1 and negative bands at 850, 679, 664, and 650 cm-1 that are specifically
associated with these two S states. The possible origins of these IR bands are
discussed. For the low-frequency QA-/QA difference spectrum, several modes can be
assigned to ring stretching and bending modes from the neutral and anion radical
states of the quinone acceptor. These results provide insight into the PSII/OEC
and demonstrate the utility of FTIR techniques in accessing low-frequency modes
in proteins.
PMID- 10194376
TI - Electron and proton transfer on the acceptor side of the reaction center in
chromatophores of Rhodobacter capsulatus: evidence for direct protonation of the
semiquinone state of QB.
AB - 1. The absorption changes associated with the formation of P+QBred (QBred stands
for the semiquinone state of the secondary quinone acceptor) were investigated in
chromatophores of Rhodobacter capsulatus. Marked modifications of the semiquinone
spectrum were observed when the pH was lowered from 7 to 5. These modifications
match those expected for a complete conversion of QBred from the anionic state QB
at pH 7 to the neutral protonated state QBH at pH 5. Similar modifications were
observed in chromatophores from Rb. sphaeroides, but not in purified reaction
centers from Rb. capsulatus, suggesting that the environment of the reaction
center (native membrane vs detergent micelle) is the crucial parameter. 2. The
recombination reaction P+QBred --> PQB was investigated as a function of pH. No
particular kinetic heterogeneity was observed at low pH, showing that QBH remains
mostly bound to the reaction center. The rate constant reaches a minimum value of
0.08 s-1 at pH 6, suggesting that the direct route for recombination prevails in
chromatophores below this pH, instead of the usual pathway via QA-. 3. The proton
uptake caused by QBred is about 1 below pH 7 and decreases at higher pH. It is
suggested that the pH dependence of the conversion of QB- to QBH, occurring in a
range where the uptake is constant, cannot be accommodated by a purely
electrostatic model, but probably involves a conformational change. 4. The
kinetics of the electron-transfer reaction QA-QB-->QAQBred were investigated. A 2
fold acceleration was observed between pH 7 and pH 5 (t1/2 approximately 30 and
15 microseconds, respectively). A fast (<<10 microseconds) unresolved phase
appears to be present at both pHs. The second electron-transfer QA-QBred-->QAQBH2
proceeds with a similar rate as the first electron transfer (15-30 microseconds
phase). Consequences for the rate-limiting step are discussed. 5. The carotenoid
shift, indicative of the membrane potential, displays a rising phase concomitant
with the QA-QB-->QAQBred electron transfer. Its relative extent is markedly
increased at pH 5, with part of the kinetics occurring during the unresolved fast
phase. 6. The extent of the electrochromic shift of bacteriopheophytin around 750
nm associated with formation of QBred decreases toward acidic pH, reflecting the
charge compensation due to proton uptake and the formation of neutral QBH.
PMID- 10194377
TI - Circular permutation of granulocyte colony-stimulating factor.
AB - The sequence of granulocyte colony-stimulating factor (G-CSF) has been circularly
permuted by introducing new chain termini into interhelical loops and by
constraining the N- and C-terminal helices, either by direct linkage of the
termini (L0) or by substitution of the amino-terminal 10-residue segment with a
seven-residue linker composed of glycines and serines (L1). All the circularly
permuted G-CSFs (cpG-CSFs) were able to fold into biologically active structures
that could recognize the G-CSF receptor. CD and NMR spectroscopy demonstrated
that all of the cpG-CSFs adopted a fold similar to that of the native molecule,
except for one [cpG-CSF(L1)[142/141]] which has the new termini at the end of
loop 34 with the shorter L1 linker. All of the cpG-CSFs underwent cooperative
unfolding by urea, and a systematically lower free energy change (DeltaGurea) was
observed for molecules with the shorter L1 linker than for those molecules in
which the original termini were directly linked (the L0 linker). The
thermodynamic stability of the cpG-CSFs toward urea was found to correlate with
their relative ability to stimulate proliferation of G-CSF responsive cells.
Taken together, these results indicate that the G-CSF sequence is robust in its
ability to undergo linear rearrangement and adopt a biologically active
conformation. The choice of linker, with its effect on stability, seems to be
important for realizing the full biological activity of the three-dimensional
structure. The breakpoint and linker together are the ultimate determinants of
the structural and biological profiles of these circularly permuted cytokines. In
the following paper [McWherter, C. A., et al. (1999) Biochemistry 38, 4564-4571],
McWherter and co-workers have used circularly permuted G-CSF sequences to
engineer chimeric dual IL-3 and G-CSF receptor agonists in which the relative
spatial orientation of the receptor agonist domains is varied. Interpreting the
differences in activity for the chimeric molecules in terms of the connectivity
between domains depends critically on the results reported here for the isolated
cpG-CSF domains.
PMID- 10194378
TI - Circular permutation of the granulocyte colony-stimulating factor receptor
agonist domain of myelopoietin.
AB - Myelopoietins (MPOs) are a family of engineered dual interleukin-3 (IL-3) and
granulocyte colony-stimulating factor (G-CSF) receptor agonists that are superior
in comparison to the single agonists in their ability to promote the growth and
maturation of hematopoietic cells of the myeloid lineage. A series of MPO
molecules were created which incorporated circularly permuted G-CSF (cpG-CSF)
sequences with an IL-3 receptor (IL-3R) agonist moiety attached at locations that
correspond to the loops that connect the helices of the G-CSF four-helix bundle
structure. The cpG-CSF linkage sites (using the original sequence numbering) were
residue 39, which is at the beginning of the first loop connecting helices 1 and
2; residue 97, which is in the turn connecting helices 2 and 3; and residues 126,
133, and 142, which are at the beginning, middle, and end, respectively, of the
loop connecting helices 3 and 4. The N- and C-terminal helices of each cpG-CSF
domain were constrained, either by direct linkage of the termini (L0) or by
replacement of the amino-terminal 10-residue segment with a seven-residue linker
composed of SGGSGGS (L1). All of the MPO molecules stimulated the proliferation
of both IL-3-dependent (EC50 = 13-95 pM) and G-CSF-dependent (EC50 = 35-710 pM)
cell lines. MPOs with the IL-3R agonist domain linked to cpG-CSFs in the first
(residue 39) or second (residue 133) long overhand loops were found by CD
spectroscopy to have helical contents similar to that expected for a protein
comprised of two linked four-helix bundles. The MPOs retained the ability to bind
to the IL-3R with affinities similar to that of the parental MPO. Using both a
cell surface competitive binding assay and surface plasmon resonance detection of
binding kinetics, the MPOs were found to bind to the G-CSF receptor with low
nanomolar affinities, similar to that of G-CSF(S17). In a study of isolated cpG
CSF domains [Feng, Y., et al. (1999) Biochemistry 38, 4553-4563], domains with
the L1 linker had lower G-CSF receptor-mediated proliferative activities and
conformational stabilities than those which had the L0 linker. A similar trend
was found for the MPOs in which the G-CSFR agonist activity is mostly a property
of the cpG-CSF domain. Important exceptions were found in which the linkage to
the IL-3R agonist domain either restored (e.g., attachment at residue 142) or
further decreased (linkage at residue 39) the G-CSFR-mediated proliferative
activity. MPO in which the IL-3R agonist domain is attached to the cpG
CSF(L1)[133/132] domain was shown to be more potent than the coaddition of the IL
3R agonist and G-CSF in stimulating the production of CFU-GM colonies in a human
bone marrow-derived CD34+ colony-forming unit assay. Several MPOs also had
decreased proinflammatory activity in a leukotriene C4 release assay using N
formyl-Met-Leu-Phe-primed human monocytes. It was found that circular permutation
of the G-CSF domain can alter the ratio of G-CSFR:IL-3R agonist activities,
demonstrating that it is a useful tool in engineering chimeric proteins with
therapeutic potential.
PMID- 10194379
TI - Plasmin desensitization of the PAR1 thrombin receptor: kinetics, sites of
truncation, and implications for thrombolytic therapy.
AB - It has been hypothesized that protease-activated receptors may be activated and
attenuated by more than one protease. Here, we explore a desensitization
mechanism of the PAR1 thrombin receptor by anticoagulant proteases and provide an
explanation to the enigma of why plasmin/tissue plasminogen activator (t-PA) can
both activate and deactivate platelets prior to thrombin treatment. By using a
soluble N-terminal exodomain (TR78) as a model for the full-length receptor, we
were able to unambiguously compare cleavage rates and specificities among the
serum proteases. Thrombin cleaves TR78 at the R41-S42 peptide bond with a kcat of
120 s-1 and a KM of 16 microM to produce TR62 (residues 42-103). We found that,
of the anticoagulant proteases, only plasmin can rapidly truncate the soluble
exodomain at the R70/K76/K82 sites located on a linker region that tethers the
ligand to the body of the receptor. Plasmin cleavage of the TR78 exodomain is
nearly equivalent to that of thrombin cleavage at R41 with similar rates (kcat =
30 s-1) and affinity (KM = 18 microM). Specificity was demonstrated since there
is no observed cleavage at the five other potential plasmin-cleavage sites.
Plasmin also cleaves the TR78 exodomain at the R41 thrombin-cleavage site
generating transiently activated exodomain. We directly demonstrated that plasmin
cleaves these same sites in full-length membrane-embedded receptor expressed in
yeast and COS7 fibroblasts. The rate of plasmin truncation is similar between the
extensively glycosylated COS7-expressed receptor and the nonglycosylated yeast
produced receptor. Mutation of the R70/K76/K82 sites to A70/A76/A82 eliminates
plasmin truncation and desensitization of thrombin-dependent Ca2+ signaling and
converts PAR1 into a plasmin-activated receptor with full agonist activity for
plasmin. Plasmin does not desensitize the Ca2+ response of platelets or COS7
cells to SFLLRN consistent with intermolecular ligand-binding sites being located
to the C-terminal side of K82. Truncation of the wild-type receptor at the C
terminal plasmin-cleavage sites removes the N-terminal tethered ligand or
preligand, thereby providing an effective pathway for PAR1 desensitization in
vivo.
PMID- 10194380
TI - Subunit affinities and stoichiometries of the human papillomavirus type 11
E1:E2:DNA complex.
AB - The association between the papillomavirus E1 and E2 proteins is an important
regulatory interaction, imparting coordinated control of viral transcription and
replication. Using fluorescence polarization, we have characterized the
interactions between HPV-11 E1, HPV-11 E2, and DNA in solution at equilibrium.
For these studies, two double-stranded fluorescein-labeled oligonucleotides were
prepared. The first fluorescent oligonucleotide, designated Fl-E2BS and
containing a single E2 binding-site palindrome (ACCGN6CGGT), was used to
determine the affinity of E2 for its DNA binding site. HPV-11 E2 bound Fl-E2BS
with an apparent Kd of 0.84 nM. Binding was saturable and consistent with a
single class of noninteracting sites. The second oligonucleotide, designated Fl
E1E2BS, contained both E1 and E2 sites in sequence derived directly from the HPV
11 origin of replication. Under titration conditions identical to those used for
Fl-E2BS, the E2 protein exhibited reduced affinity for Fl-E1E2BS (Kd > 100 nM).
E1 binding to Fl-E1E2BS was of very low affinity. Addition of excess HPV-11 E1 to
Fl-E1E2BS lowered the dissociation constant for the E2:Fl-E1E2BS interaction to 2
nM. This effect was not dependent upon ATP or magnesium ion. Fluorescence
polarization and other data suggest formation of a complex containing six E1
molecules and a single dimer of E2 bound to a single Fl-E1E2BS oligonucleotide;
E2 dissociation from the final complex did not occur. In summary, physical
interaction between E1 and E2 increases the DNA binding affinity of each. The
role of this energy coupling may be to promote origin-specific binding of both E1
and E2 to DNA.
PMID- 10194381
TI - Differential effects of apolipoprotein E isoforms on metal-induced aggregation of
A beta using physiological concentrations.
AB - The epsilon 4 allele of apolipoprotein E (APOE) has been found to be a risk
factor for late-onset Alzheimer's disease (AD). While the pathogenic mechanism of
APOE in AD is not yet clear, APOE isoforms appear to differentially influence the
aggregation of A beta, the principal component of Alzheimer-associated beta
amyloid deposits. To date, no data are available for the propensity of A beta to
aggregate in the presence of APOE under conditions where these components are at
physiological concentrations (in cerebrospinal fluid, APOE and A beta are
approximately 100 nM and approximately 5 nM, respectively). We employed a novel
in vitro filtration assay for detecting zinc(II)- and copper(II)-induced
aggregation of A beta in solutions containing concentrations of the peptide that
are similar to those reported for human cerebrospinal fluid. The potential for
resolubilization with EDTA and the relative densities of zinc- and copper-induced
A beta aggregates were also compared. Zinc-induced A beta aggregates were found
to be denser and less easily resolubilized than copper-induced precipitates.
Metal-induced aggregation of A beta was studied in the presence of purified
apolipoprotein E2, apolipoprotein E3, and apolipoprotein E4 under conditions that
approximate the physiological concentrations and ratios of these proteins. In the
presence of all three APOE isoforms, zinc-induced aggregation of A beta was
attenuated, while precipitation with copper was enhanced. Consistent with the
increased risk for AD associated with the epsilon 4 allele of APOE, metal-induced
aggregation of A beta was highest for both zinc and copper in the presence of
apolipoprotein E4. Our data are consistent with a role for APOE as an in vivo
molecular chaperone for A beta.
PMID- 10194382
TI - Lysophosphatidylcholine modulates catalytically important motions of the Ca
ATPase phosphorylation domain.
AB - Catalytically important motions of the Ca-ATPase, modulated by the physical
properties of surrounding membrane phospholipids, have been suggested to be rate
limiting under physiological conditions. To identify the nature of the structural
coupling between the Ca-ATPase and membrane phospholipids, we have investigated
the functional and structural effects resulting from the incorporation of the
lysophospholipid 1-myristoyl-2-hydroxy-sn-glycerol-3-phosphocholine (LPC) into
native sarcoplasmic reticulum (SR) membranes. Nonsolubilizing concentrations of
LPC abolish changes in fluorescence signals associated with either intrinsic or
extrinsic chromophores that monitor normal conformational transitions
accompanying calcium activation of the Ca-ATPase. There are corresponding
decreases in the rates of calcium transport coupled to ATP hydrolysis, suggesting
that LPC may increase conformational barriers associated with catalytic function.
Fluorescence anisotropy measurements of the lipid analogue 1-(4
trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH) partitioned into SR
membranes indicate that LPC does not significantly modify lipid acyl chain
rotational dynamics, suggesting differences in headgroup conformation between LPC
and diacylglycerol phosphatidylcholines. Complementary measurements using
phosphorescence anisotropy of erythrosin isothiocyanate at Lys464 on the Ca
ATPase provide a measure of the dynamic structure of the phosphorylation domain,
and indicate that LPC restricts the amplitude of rotational motion. These results
suggest a structural linkage between the cytosolic phosphorylation domain and the
conformation of membrane phospholipid headgroups. Thus, changes in membrane
phospholipid composition can modulate membrane surface properties and affect
catalytically important motions of the Ca-ATPase in a manner that suggests a role
for LPC generated during signal transduction.
PMID- 10194383
TI - Thermodynamic stability of a cold-active alpha-amylase from the Antarctic
bacterium Alteromonas haloplanctis.
AB - The thermal stability of the cold-active alpha-amylase (AHA) secreted by the
Antarctic bacterium Alteromonas haloplanctis has been investigated by intrinsic
fluorescence, circular dichroism, and differential scanning calorimetry. It was
found that this heat-labile enzyme is the largest known multidomain protein
exhibiting a reversible two-state unfolding, as demonstrated by the recovery of
DeltaHcal values after consecutive calorimetric transitions, a
DeltaHcal/DeltaHeff ratio close to unity, and the independence of unfolding
thermodynamic parameters of scan rates. By contrast, the mesophilic alpha
amylases investigated here (from porcine pancreas, human salivary glands, yellow
meal beetle, Bacillus amyloliquefaciens, and Bacillus licheniformis) unfold
irreversibly according to a non-two-state mechanism. Unlike mesophilic alpha
amylases, the melting point of AHA is independent of calcium and chloride binding
while the allosteric and structural functions of these ions are conserved. The
thermostability of AHA at optimal conditions is characterized by a Tm of 43.7
degrees C, a DeltaHcal of 238 kcal mol-1, and a DeltaCp of 8.47 kcal mol-1 K-1.
These values were used to calculate the Gibbs free energy of unfolding over a
wide range of temperatures. This stability curve shows that (a) the specific
DeltaGmax of AHA [22 cal (mol of residue)-1] is 4 times lower than that of
mesophilic alpha-amylases, (b) group hydration plays a crucial role in the enzyme
flexibility at low temperatures, (c) the temperature of cold unfolding closely
corresponds to the lower limit of bacterial growth, and (d) the recombinant heat
labile enzyme can be expressed in mesophilic hosts at moderate temperatures. It
is also argued that the cold-active alpha-amylase has evolved toward the lowest
possible conformational stability of its native state.
PMID- 10194384
TI - Phosphorylation of the major Drosophila lamin in vivo: site identification during
both M-phase (meiosis) and interphase by electrospray ionization tandem mass
spectrometry.
AB - Phosphorylation can have profound effects on the properties of nuclear lamins.
For instance, phosphorylation of specific sites on mammalian lamins drastically
alters their propensity to polymerize. Relatively little is known about the
effects of phosphorylation during interphase and about phosphorylation of
invertebrate nuclear lamins. Here, using electrospray ionization tandem mass
spectrometry, we determined the phosphorylation sites of both interphase and M
phase isoforms of nuclear lamin Dm from Drosophila melanogaster. Interphase
lamins are phosphorylated at three sites: two of these sites (Ser25 and a site
located between residues 430 and 438) flank the alpha-helical rod domain, whereas
the third site (Ser595) is located close to the C-terminus. The M-phase lamin
isoform is phosphorylated predominantly at Ser45, a residue contained within a
sequence matching the consensus site for phosphorylation by cdc2 kinase. Our
study confirms the important role in vivo for cdc2 kinase in M-phase disassembly
of nuclear lamins and provides the basis for understanding Drosophila lamin
phosphorylation during interphase.
PMID- 10194385
TI - Thermodynamic study of phosphoglycerate kinase from Thermotoga maritima and its
isolated domains: reversible thermal unfolding monitored by differential scanning
calorimetry and circular dichroism spectroscopy.
AB - The folding of phosphoglycerate kinase (PGK) from the hyperthermophilic bacterium
Thermotoga maritima and its isolated N- and C-terminal domains (N1/2 and C1/2)
was characterized by differential scanning calorimetry (DSC) and circular
dichroism (CD) spectroscopy. At pH 3.0-4.0, reversible thermal denaturation of
TmPGK occurred below 90 degrees C. The corresponding peaks in the partial molar
heat capacity function were fitted by a four-state model, describing three well
defined unfolding transitions. Using CD spectroscopy, these are ascribed to the
disruption of the domain interactions and subsequent sequential unfolding of the
two domains. The isolated N-terminal domain unfolds reversibly between pH 3.0 and
pH 4.0 to >90% and at pH 7.0 to about 70%. In contrast, the isolated engineered C
terminal domain only shows reversible thermal denaturation between pH 3.0 and pH
3.5. Neither N1/2 nor C1/2 obeys the simple two-state mechanism of unfolding.
Instead, both unfold via a partially structured intermediate. In the case of
N1/2, the intermediate exhibits native secondary structure and perturbed tertiary
structure, whereas for C1/2 the intermediate could not be defined with certainty.
PMID- 10194386
TI - A new method for determining the stereochemistry of DNA cleavage reactions:
application to the SfiI and HpaII restriction endonucleases and to the MuA
transposase.
AB - A new method was developed for tracking the stereochemical path of enzymatic
cleavage of DNA. DNA with a phosphorothioate of known chirality at the scissile
bond is cleaved by the enzyme in H218O. The cleavage produces a DNA molecule with
the 5'-[16O,18O, S]-thiophosphoryl group, whose chirality depends on whether the
cleavage reaction proceeds by a single-step hydrolysis mechanism or by a two-step
mechanism involving a protein-DNA covalent intermediate. To determine this
chirality, the cleaved DNA is joined to an oligonucleotide by DNA ligase. Given
the strict stereochemistry of the DNA ligase reaction, determined here, the
original chirality of the phosphorothioate dictates whether the 18O is retained
or lost in the ligation product, which can be determined by mass spectrometry.
This method has advantages over previous methods in that it is not restricted to
particular DNA sequences, requires substantially less material, and avoids
purification of the products at intermediate stages in the procedure. The method
was validated by confirming that DNA cleavage by the EcoRI restriction
endonuclease causes inversion of configuration at the scissile phosphate. It was
then applied to the reactions of the SfiI and HpaII endonucleases and the MuA
transposase. In all three cases, DNA cleavage proceeded with inversion of
configuration, indicating direct hydrolysis of the phosphodiester bond by water
as opposed to a reaction involving a covalent enzyme-DNA intermediate.
PMID- 10194387
TI - Chloride binding regulates the Schiff base pK in gecko P521 cone-type visual
pigment.
AB - The binding of chloride is known to shift the absorption spectrum of most long
wavelength-absorbing cone-type visual pigments roughly 30 nm to the red. We
determined that the chloride binding constant for this color shift in the gecko
P521 visual pigment is 0.4 mM at pH 6.0. We found an additional effect of
chloride on the P521 pigment: the apparent pKa of the Schiff base in P521 is
greatly increased as the chloride concentration is increased. The apparent Schiff
base pKa shifts from 8.4 for the chloride-free form to >10.4 for the chloride
bound form. We show that this shift is due to chloride binding to the pigment,
not to the screening of the membrane surface charges by chloride ions. We also
found that at high pH, the absorption maximum of the chloride-free pigment shifts
from 495 to 475 nm. We suggest that the chloride-dependent shift of the apparent
Schiff base pKa is due to the deprotonation of a residue in the chloride binding
site with a pKa of ca. 8.5, roughly that of the Schiff base in the absence of
chloride. The deprotonation of this site results in the formation of the 475 nm
pigment and a 100-fold decrease in the pigment's ability to bind chloride.
Increasing the concentration of chloride results in the stabilization of the
protonated state of this residue in the chloride binding site and thus increased
chloride binding with an accompanying increase in the Schiff base pK.
PMID- 10194388
TI - Application of enzymes in the pulp and paper industry
AB - The pulp and paper industry processes huge quantities of lignocellulosic biomass
every year. The technology for pulp manufacture is highly diverse, and numerous
opportunities exist for the application of microbial enzymes. Historically,
enzymes have found some uses in the paper industry, but these have been mainly
confined to areas such as modifications of raw starch. However, a wide range of
applications in the pulp and paper industry have now been identified. The use of
enzymes in the pulp and paper industry has grown rapidly since the mid 1980s.
While many applications of enzymes in the pulp and paper industry are still in
the research and development stage, several applications have found their way
into the mills in an unprecedented short period of time. Currently the most
important application of enzymes is in the prebleaching of kraft pulp. Xylanase
enzymes have been found to be most effective for that purpose. Xylanase
prebleaching technology is now in use at several mills worldwide. This technology
has been successfully transferred to full industrial scale in just a few years.
The enzymatic pitch control method using lipase was put into practice in a large
scale paper-making process as a routine operation in the early 1990s and was the
first case in the world in which an enzyme was successfully applied in the actual
paper-making process. Improvement of pulp drainage with enzymes is practiced
routinely at mill scale. Enzymatic deinking has also been successfully applied
during mill trials and can be expected to expand in application as increasing
amounts of newsprint must be deinked and recycled. The University of Georgia has
recently opened a pilot plant for deinking of recycled paper. Pulp bleaching with
a laccase mediator system has reached pilot plant stage and is expected to be
commercialized soon. Enzymatic debarking, enzymatic beating, and reduction of
vessel picking with enzymes are still in the R&D stage but hold great promise for
reducing energy. Other enzymatic applications, i.e., removal of shives and slime,
retting of flax fibers, and selective removal of xylan, are also expected to have
a profound impact on the future technology of the pulp and paper-making process.
PMID- 10194389
TI - Expression of Vitreoscilla hemoglobin in Escherichia coli enhances ribosome and
tRNA levels: a flow field-flow fractionation study.
AB - Asymmetrical flow field-flow fractionation (FFF) was used to separate and
quantitate 70S ribosomes, the 30S and 50S subunits, and tRNA in one single
analytical procedure. The method was applied to an investigation of the effect of
Vitreoscilla hemoglobin (VHb) on the translational machinery of the recombinant
Escherichia coli cells. The number of active 70S ribosomes per cell increased
dramatically, more than 2-fold, as did also the tRNA levels for the VHb
expressing strain relative to VHb-negative control at the end of a 30-h fed-batch
cultivation. This was accompanied by a corresponding 61% increase of a cloned
marker enzyme activity. The results clearly indicate that VHb promotes the level
of translational components. There should be many other cases in bioengineering
where it is important to relate the protein production level in a bioreactor to
the ribosome and tRNA levels.
PMID- 10194390
TI - Secretory production of recombinant protein by a high cell density culture of a
protease negative mutant Escherichia coli strain.
AB - Several protease negative mutant strains including HM114, HM126, and HM130 as
well as their parent strain KS272 were compared for their growth and secretory
production of a model fusion protein, protein A-beta-lactamase. HM114, a strain
deficient in two cell envelope proteases, grew slightly faster and produced more
fusion protein than the other strains deficient in more proteases. HM114 was
grown to a cell dry weight of 47.86 g/L in 29 h using pH-stat, fed-batch
cultivation. The beta-lactamase activity was 11.25 x 10(4) U/L, which was 30%
higher than that obtained with its parent strain KS272. Up to 96% of protein A
beta-lactamase fusion protein could be recovered by a simple cold osmotic shock
method. The specific beta-lactamase activity obtained with HM114 after
fractionation was 4.5 times higher than that obtained with KS272.
PMID- 10194391
TI - Use of mannosamine for inducing the addition of outer arm N-acetylglucosamine
onto N-linked oligosaccharides of recombinant proteins in insect cells.
AB - Glycosylation is a cellular process accomplished by a series of sequential
enzymatic processing steps through the endoplasmic reticulum and Golgi apparatus
with vesicle transport between the membranous organelles. The capacity for
complex glycosylation is considered to be conferred by cell genetics, while the
roles of nongenetic factors in protein processing are often ignored. It was
hypothesized that the glycosyltransferase reactions in the insect cell
baculovirus system were limited by the small supply of sugar donor cosubstrates.
By adding mannosamine, the glycosylation of a human secreted alkaline phosphatase
in Spodoptera frugiperda (Sf-21) cells was extended to include terminal N
acetylglucosamine structures which were not seen in control cultures, and in
Trichoplusic ni (BTI-Tn5B1-4) cells the amount of terminal N-acetylglucosamine
structures was increased.
PMID- 10194392
TI - Application of a fed-batch system to produce RNA by in vitro transcription.
AB - A novel fed-batch method is presented for the production of RNA by in vitro
transcription performed in a stirred-cell reactor with pH-controlled addition of
reaction components. Solution equilibrium analysis is applied to determine the
ratios of feed components (including nucleoside triphosphates (NTPs), magnesium
salt, and base) which allow the desired NTP concentrations, free magnesium
concentration, and pH to be maintained during the reaction. Results are presented
for fed-batch and batch reactions performed with two DNA templates encoding a
12mer RNA and a 38mer RNA. For the dodecamer RNA, the fed-batch mode is only
modestly better than batch reactions, with no significant increase in the
efficiency of NTP incorporation but with 40% improvement in the amount of RNA
produced per unit of polymerase or DNA. For the 38mer, fed-batch transcription
provides a substantial increase in the efficiency of NTP incorporation and 100%
improvement in the production of RNA per unit of polymerase or DNA. Cost analyses
are presented which show how optimal NTP concentrations in batch and fed-batch
reactions will be dependent on the relative costs of NTPs, T7 RNA polymerase, and
DNA templates for the particular application. The use of a fed-batch mode appears
to have the potential for substantial improvement in the economics of RNA
production for at least some RNA sequences.
PMID- 10194393
TI - Performance trade-offs in in situ chemostat NMR.
AB - Investigating cell cultures with NMR requires high cell densities to provide
adequate signal-to-noise, or scans must be summed over long time periods and
short-term events are lost. The mixing within a chemostat can be used to shorten
the time required to acquire informative in situ NMR spectra from cell cultures.
However, performance trade-offs can occur between net signal, spectral
resolution, and oxygenation due to sampling volume, conductivity, gas bubble, and
fluid flow effects. These trade-offs and the effect of different mixing regimes
were theoretically analyzed to quantify how device design decisions impact
performance. The results were found to concur with data from cell-free NMR
experiments performed in 18 mS/cm conductivity medium. The results also guided
the redesign of an NMR bioreactor in terms of relative radio frequency (rf) coil
and sample dimensions and other factors. The design, which entails using
chemostat mixing to shunt sample through a rf coil in ca. 0.4 s, provides
adequate oxygenation for the 4-16% (v/v) cell suspensions examined. Gains
realized include lower conductive losses, better magnetic field homogeneity, and
the exclusion of gas bubbles from the sampling zone. These gains enable the
acquistion of spectra from dilute (3-4% v/v) Saccharomyces cerevisiae chemostat
cultures in 6.9 min with high resolution in both the orthophosphate and the beta
NTP regions. Samples with 16% (v/v) cells also yield useful spectra within 0.5
1.0 min.
PMID- 10194394
TI - Modification of the carbohydrate composition of sulfite pulp by purified and
characterized beta-xylanase and beta-xylosidase of Aureobasidium pullulans.
AB - Both beta-xylanase and beta-xylosidase were purified to homogeneity from a xylose
grown culture of Aureobasidium pullulans. Cellular distribution studies of enzyme
activities revealed that beta-xylanase was an extracellular enzyme, during both
the exponential and stationary phases, whereas beta-xylosidase was mostly
periplasmic associated. The beta-xylanase exhibited very high specificity for
xylan extracted from Eucalyptus grandis dissolving pulp, whereas the beta
xylosidase was only active on p-nitrophenyl xyloside and xylobiose. Comparison of
kcat/Km ratios showed that the beta-xylanase hydrolyzed xylan from dissolving
pulp 1.3, 2.1, and 2. 3 times more efficiently than Eucalyptus hemicellulose B,
Eucalyptus hemicellulose A, and larchwood xylan, respectively. The beta
xylosidase exhibited a transxylosylation reaction during the hydrolysis of
xylobiose. When applied on acid sulfite pulp, both enzymes released xylose and
hydrolyzed xylan to a different extent. Although beta-xylosidase (0.4 U/g pulp)
liberated more xylose from pulp than beta-xylanase (4.7 U/g pulp), it was
responsible for only 3% of xylan solubilization. Treatment of pulp with beta
xylanase liberated 51.7 microgram of xylose/g and hydrolyzed 10% of xylan. The
two enzymes acted additively on pulp and removed 12% of pulp xylan. A synergistic
effect in terms of release of xylose from pulp was observed when the enzyme
mixture of beta-xylanase and beta-xylosidase was supplemented with beta
mannanase. However, this did not result in further enzymatic degradation of pulp
xylan. Both beta-xylanase and beta-xylosidase altered the carbohydrate
composition of sulfite pulp by increasing the relative cellulose content at the
expense of reduced hemicellulose content of pulp.
PMID- 10194395
TI - Metabolic pathway of Propionibacterium growing with oxygen: enzymes, 13C NMR
analysis, and its application for vitamin B12 production with periodic
fermentation.
AB - The metabolic pathway of Propionibacterium grown under an aerobic condition is
still not clear so far. In this work, cell growth, organic acid formation,
vitamin B12 synthesis, and enzyme activities were determined in different aerobic
cultivation systems. It was found that the propionate, which is accumulated
during anaerobic cultivation, was completely decomposed when the cultivation was
shifted to an aerobic condition. Moreover, pyruvate was formed in accordance with
the decomposition of the propionate. Besides, more acetate was produced and a
large amount of malate was formed during the aerobic cultivation. Such phenomena
could be repeatedly observed in a periodic cultivation in which the dissolved
oxygen concentration was alternatively controlled at 0 or 1 ppm. Enzyme analysis
indicates that the regulation of organic acid formation depends on which
molecule, i.e., oxygen or fumarate, serves as an electron acceptor in the
respiratory chain reactions. No tricarboxylic acid cycle was found to exist in
this species grown under an aerobic condition. It is evident that the randomizing
pathway worked in a reversed direction in the presence of oxygen, through which
the propionate is oxidized to pyruvate. The 13C NMR spectral analysis confirmed
this observation.
PMID- 10194396
TI - Hydrazide-functionalized poly(2-hydroxyethyl methacrylate) microspheres for
immobilization of horseradish peroxidase.
AB - Nonporous cross-linked poly(2-hydroxyethyl methacrylate-co-ethylene
dimethacrylate) (poly(HEMA-co-EDMA)) microspheres were prepared by dispersion
polymerization of HEMA and EDMA. The polymerization was performed in toluene/2
methylpropan-1-ol in the presence of cellulose acetate butyrate as a steric
stabilizer and dibenzoyl peroxide initiator. The particle size may be increased
by decreasing the toluene/2-methylpropan-1-ol ratio and by increasing
polymerization temperature. Adipohydrazide was attached to the microspheres
activated with 2,4,6-trichloro-1,3,5-triazine. After periodate oxidation of its
carbohydrate moieties, horseradish peroxidase was coupled to the hydrazide
functionalized poly(HEMA-co-EDMA) microparticles up to 7.3 microgram of enzyme/g
of carrier without a significant loss of its activity. Immobilized peroxidase was
found to be stable, retaining more than 97% of its initial activity when stored
for 23 days after the preparation.
PMID- 10194397
TI - Potential of enzymatic kinetic resolution using solid substrates suspension:
improved yield, productivity, substrate concentration, and recovery
AB - In the literature the enzymatic kinetic resolution of a suspension of a solid
substrate has largely been treated as a conventional kinetic resolution of a
fully dissolved substrate. In this paper it is shown that this type of kinetic
resolution is different in several important aspects. Quantitative models are
developed for two types of such suspension processes. These models are used to
compare the merits of these processes with the conventional kinetic resolution
process where fully dissolved substrate is used. In the suspension processes the
liquid phase concentration of substrate enantiomer that should be converted can
be kept close to the maximum value, i.e., the solubility, when process conditions
are properly chosen, whereas in a conventional process this concentration
gradually decreases. Calculations show that this leads to a productivity that is
about 6-fold higher in the suspension processes. Also, for enzymes with a low
enantioselectivity, a severalfold increase in yield of remaining enantiopure
substrate is predicted compared to the conventional kinetic resolution of
dissolved enantiomers. Other potential advantages of using suspension reactions
are that the initial substrate concentration may be higher (up to 25% (w/w)) and
that the desired remaining substrate may be recovered by simply filtering off the
solid crystals. Experimental evidence that these merits can be exploited is only
partly given, using the few available examples from the literature.
PMID- 10194398
TI - Biosorption of lead, cadmium, and zinc by Citrobacter strain MCM B-181:
characterization studies.
AB - The biosorption process for removal of lead, cadmium, and zinc by Citrobacter
strain MCM B-181, a laboratory isolate, was characterized. Effects of
environmental factors and growth conditions on metal uptake capacity were
studied. Pretreatment of biomass with chemical agents increased cadmium sorption
efficiency; however, there was no significant enhancement in lead and zinc
sorption capacity. Metal sorption by Citrobacter strain MCM B-181 was found to be
influenced by the pH of the solution, initial metal concentration, biomass
concentration, and type of growth medium. The metal sorption process was not
affected by the age of the culture or change in temperature. Equilibrium metal
sorption was found to fit the Langmuir adsorption model. Kinetic studies showed
that metal uptake by Citrobacter strain MCM B-181 was a fast process, requiring
<20 min to achieve >90% adsorption efficiency. The presence of cations reduced
lead, zinc, and cadmium sorption to the extent of 11. 8%, 84.3%, and 33.4%,
respectively. When biomass was exposed to multimetal solutions, metals were
adsorbed in the order Co2+ < Ni2+ < Cd2+ < Cu2+ < Zn2+ < Pb2+. Among various
anions tested, only phosphate and citrate were found to hamper metal sorption
capacity of cells. Biosorbent beads prepared by immobilizing the Citrobacter
biomass in polysulfone matrix exhibited high metal loading capacities. A new
mathematical model used for batch kinetic studies was found to be highly useful
in prediction of experimentally obtained metal concentration profiles as a
function of time. Metal desorption studies indicated that Citrobacter beads
could, in principle, be regenerated and reused in adsorption-desorption cycles.
In an expanded scale trial, biosorbent beads were found to be useful in
removal/recovery of metals such as lead from industrial wastewaters.
PMID- 10194399
TI - Capture of rare cells in suspension with antibody-coated polystyrene beads.
AB - A method for the separation of one cell type present in small number from a
predominant mixture of cell types using macroscopic polystyrene beads is
demonstrated. An antibody specific to murine leukocytes (CD45) was adsorbed to
the surface of the beads. Beads and murine hybridoma B cells were placed in test
tubes and periodically inverted at fixed time intervals, causing the beads to
settle through the suspension under creeping flow conditions. Capture was
dependent upon interception: the captured cells must have traveled along
streamlines that brought them to within a cell radius of the bead surface. B
cells attached to 99-micrometer beads (maximum shear rate 8.1 s-1) were captured
with greater efficiency but in lesser quantity than those attached to 170
micrometer beads (maximum shear rate 13.9 s-1). Cell capture unexpectedly reached
a plateau in less than 2 h, a phenomenon that appears to involve changes in both
the cells and the beads. Capture of cells was effective out to dilutions of 1:10
000 with purity in the captured population of better than 74%. This method allows
for the study of physical parameters important for cell attachment and capture as
well as for practical separation of rare cells.
PMID- 10194400
TI - Measurement of bacterial flagellar thrust by negative dielectrophoresis.
AB - The force produced by the flagella of the bacterium Salmonella typhimurium has
been measured using negative dielectrophoretic methods. The bacteria are held in
a force funnel, produced using a nonuniform electric field. When the motor force
is balanced against an opposing negative dielectrophoretic force the bacteria
become motionless. Numerical simulations have been used to estimate the electric
field gradient in the electrodes. Together with experimental observations of
bacterial motion the data gives a value of the force produced by the bacterial
motor to be 0.37 pN.
PMID- 10194401
TI - Binding of water, oil, and bile acids to dietary fibers of the cellan type.
AB - Dietary fibers (DF) of the "cellan" type (consisting mainly or exclusively of
undestroyed cells) were prepared as ethanol-dried materials from apple, cabbage,
sugar-beet, soybean hulls, wheat bran, and suspension cultures of Chenopodium
album L. and investigated with respect to their interactions with water, water
oil dispersions, bile acids, and oil. Water binding and retention capacities were
found to be especially high in cellans obtained from thin-walled raw material.
Water damp sorption by dry cellans, when analyzed according to the GAB and BET
equations, shows a considerable fraction of monolayer water. At a water activity
of 0.98, the cell and capillary spaces outside the walls remained in the air
filled state but the cell wall pores are filled with water. When the water
content of a concentrated aqueous cellan suspension was equal to or below the
water binding capacity, its rheological behavior was found to be of pseudoplastic
nature. At a given dry weight concentration, yield stress and viscosity of such
concentrated suspensions were highest for cellans with the highest water binding
capacity. Dry cellan particles absorbed fatty oils without swelling but swell in
a detergent-stabilized oil/water emulsion with a similar liquid absorption
capacity as in water. In contrast to the dry or alkane-saturated cell wall, the
hydrated wall is not permeable to oils in the absence of a detergent. Oil
droplets may be entrapped within the cells, yielding a stable dispersion of oil
in water. As DF of the cellan type absorb bile acids, preferentially
glycoconjugates, from diluted solutions, they may have a potential to decrease
the serum cholesterol level.
PMID- 10194402
TI - Modeling the response time of an in vivo glucose affinity sensor.
AB - A mathematical model was developed to describe the dose-response relationship of
an optical glucose sensor. The basis for glucose detection is the reversible
competitive displacement of a ligand from a receptor protein with specific
binding sites for certain carbohydrates. Detection of glucose is based on
measurements of the change in fluorescent lifetime of the donor-labeled protein,
as it binds to the acceptor-labeled ligand. The sensor was modeled as a hollow
fiber membrane, permeable to glucose, which encapsulates a solution of the
receptor protein and competing ligand. Model equations that describe the
diffusion of glucose through the fiber membrane and the subsequent displacement
reactions within the fiber lumen were solved numerically to predict the response
time of the sensor following a step change in bulk glucose concentration. The
incorporation of an external mass transfer boundary layer was found to increase
the response time by a factor of 3.7 over the well-stirred case. On the basis of
the results of a parametric study, the response time of the sensor was found to
be most sensitive to the diffusion coefficient of glucose in the membrane. When
compared to experimental response times for an intensity-based affinity sensor
using Concanavalin A as the receptor protein and dextran as the competing ligand,
the model predictions were found to be significantly shorter than those observed.
The effect of the in vivo environment on the performance of the sensor was also
investigated through the incorporation of a fibrotic capsule layer. The
additional diffusional resistance offered by the capsular tissue resulted in a 5
fold increase in the response time of the sensor.
PMID- 10194403
TI - Development of a cell-loaded biosupport separator for continuous immobilized-cell
perfusion culture.
AB - An efficient cell-loaded biosupport separator of the decantor type was developed
and applied for a continuous perfusion culture to produce cyclosporin A (CyA), in
which fungal cells were immobilized on Celite beads. In the preliminary
experiments employing highly viscous polymer (carboxymethyl cellulose) solutions,
the decantor showed good separation performances at high solution viscosites and
dilution rates. Two concentric cylindrical tubes installed inside the decantor
turned out to play key roles in the efficient separation of the immobilized
cells. By installing the decantor on an immobilized-cell perfusion bioprocess
system, a stable continuous operation was possible even at a high dilution rate
for an extended period, leading to high productivities of free cells and CyA.
Almost no immobilized biomass existed in the effluent stream from the bioreactor,
demonstrating the effectiveness of the decantor system. It is noteworthy that we
could obtain these results despite unfavorable fermentation conditions, i.e.,
reduced apparent density of cell-loaded beads and increased drag force on the
bead particles caused by overgrowth of cells on the bead surface, tubulence
caused by large air bubbles, and the existence of a high density of suspended
fungal cells (10 g/L) in the fermentation broth.
PMID- 10194404
TI - Single, combined, or sequential action of pressure and temperature on
lipoxygenase in green beans (Phaseolus vulgaris L.): a kinetic inactivation
study.
AB - The objective of this investigation was to study kinetically the effect of
pressure and temperature either as a single, as a combined, or as a sequential
action on lipoxygenase (LOX) inactivation in crude green beans extract. The LOX
isozymes in green beans extract had a different heat sensitivity but a similar
pressure stability: two fractions following apparent first-order reactions, i.e.,
a heat-labile fraction and a heat-stable fraction, were observed in studies on
its thermostability, whereas only one fraction following a first-order reaction
was noticed in studies on its pressure stability. At ambient pressure,
irreversible LOX inactivation was studied in a temperature range from 55 to 70
degrees C. At room temperature, pressures around 500 MPa were required in order
to inactivate LOX in green beans extract. The effect of a pressure or a thermal
pretreatment on LOX thermo- or barostability, respectively, was also investigated
but no significant differences in inactivation kinetics due to the pretreatment
were observed.
PMID- 10194405
TI - Direct Agrobacterium tumefaciens-mediated transformation of Hyoscyamus muticus
hairy roots using green fluorescent protein.
AB - Hyoscyamus muticus hairy root segments were infected with Agrobacterium
tumefaciens ASE containing the binary vector pCGN1548 with a green fluorescent
protein (GFP) reporter gene under the control of the CaMV 35S promoter. The roots
were incubated on callus-inducing medium to generate transformed cells.
Transformants were selected on medium containing 50 and 100 mg/L kanamycin and
screened by visual inspection for GFP expression. Highly fluorescent cells were
incubated on phytohormone-free medium for regeneration of the hairy root
phenotype. This infection technique can be applied directly to existing hairy
root cultures which have been previously characterized and selected for desirable
physiological traits. These studies also indicate that GFP is not toxic to H.
muticus plant tissue and that H. muticus hairy roots have minimal
autofluorescence which allows for clear observation of GFP.
PMID- 10194406
TI - Purification of human interleukin-2 fusion protein produced in insect larvae is
facilitated by fusion with green fluorescent protein and metal affinity ligand.
AB - The fusion protein of green fluorescent protein (GFP) and human interleukin-2
(hIL-2) was produced in insect Trichoplusia ni larvae infected with recombinant
baculovirus derived from the Autographa californica nuclear polyhedrosis virus
(AcNPV). This fusion protein was composed of a metal ion binding site (His)6 for
rapid one-step purification using immobilized metal affinity chromatography
(IMAC), UV-optimized GFP (GFPuv), enterokinase cleavage site for recovering hIL-2
from purified fusion protein, and hIL-2 protein. The additional histidine
residues on fusion protein enabled the efficient purification of fusion protein
based on immobilized metal affinity chromatography. In addition to advantages of
GFP as a fusion marker, GFP was able to be used as a selectable purification
marker; we easily determined the correct purified fusion protein sample fraction
by simply detecting GFP fluorescence.
PMID- 10194407
TI - Examining the relationship between the gelatinolytic balance and the invasive
capacity of endothelial cells.
AB - Angiogenesis and the formation of new blood vessels requires coordinated
regulation of matrix proteolysis and endothelial cell migration. Cellular
proteolytic capacity is the balance between secreted matrix metalloproteinases
(MMP) and their inhibitors (TIMPs). We have examined the regulation of the
gelatinase/TIMP balance by transforming growth factor-beta1 (TGF-beta1) and
phorbol myristate acetate (PMA) in bovine endothelial cells. The low constitutive
expression of gelatinase A/MMP-2 was upregulated by TGF-beta1 in a dose-dependent
manner. Gelatinase B/MMP-9 was only detected upon treatment with either PMA or
TGF-beta1. However, addition of both factors together revealed a striking
synergistic effect causing upregulation of MMP-9 and downregulation of TIMPs,
thereby increasing the net MMP-9/TIMP balance and the gelatinolytic capacity.
These effects were observed at both the protein and mRNA levels. We demonstrate
that changes in different members of the Jun oncogene family with distinct
transactivation properties may account for this synergistic effect. We
investigated the contribution of these changes in gelatinolytic balance to
endothelial cell migration and invasion. The endothelial cells showed increased
cell motility in response to PMA, but the addition of TGF-beta1 had an inhibitory
effect. Hence, regulation of the MMP-9/TIMP balance failed to correlate with the
migratory or invasive capacity. These results question a direct role for MMP-9 in
endothelial cell motility and suggest that gelatinases may contribute in
alternative ways to the angiogenic process.
PMID- 10194409
TI - Inhibition of clathrin-coated pit assembly by an Eps15 mutant.
AB - Recent data have shown that Eps15, a newly identified component of clathrin
coated pits constitutively associated with the AP-2 complex, is required for
receptor-mediated endocytosis. However, its precise function remains unknown.
Interestingly, Eps15 contains three EH (Eps15-Homology) domains also found in
proteins required for the internalization step of endocytosis in yeast. Results
presented here show that EH domains are required for correct coated pit targeting
of Eps15. Furthermore, when cells expressed an Eps15 mutant lacking EH domains,
the plasma membrane punctate distribution of both AP-2 and clathrin was lost,
implying the absence of coated pits. This was further confirmed by the fact that
dynamin, a GTPase found in coated pits, was homogeneously redistributed on the
plasma membrane and that endocytosis of transferrin, a specific marker of
clathrin-dependent endocytosis, was strongly inhibited. Altogether, these results
strongly suggest a role for Eps15 in coated pit assembly and more precisely a
role for Eps15 in the docking of AP-2 onto the plasma membrane. This hypothesis
is supported by the fact that a GFP fusion protein encoding the ear domain of
(alpha)-adaptin, the AP-2 binding site for Eps15, was efficiently targeted to
plasma membrane coated pits.
PMID- 10194408
TI - Dynein is required for spindle assembly in cytoplasmic extracts of Spisula
solidissima oocytes.
AB - Meiosis I spindle assembly is induced in lysate-extract mixtures prepared from
clam (Spisula solidissima) oocytes. Unactivated lysate prepared from unactivated
oocytes contain nuclei (germinal vesicles, GVs) which house condensed
chromosomes. Treatment of unactivated lysate with clarified activated extract
prepared from oocytes induced to complete meiosis by treatment with KCl induces
GV breakdown (GVBD) and assembly of monopolar, bipolar, and multipolar aster
chromosome complexes. The process of in vitro meiosis I spindle assembly involves
the assembly of microtubule asters and the association of these asters with the
surfaces of the GVs, followed by GVBD and spindle assembly. Monoclonal antibody
m74-1, known to react specifically with the N terminus of the intermediate chain
of cytoplasmic dynein, recognizes Spisula oocyte dynein and inhibits in vitro
meiosis I spindle assembly. Control antibody has no affect on spindle assembly. A
similar inhibitory effect on spindle assembly was observed in the presence of
orthovanadate, a known inhibitor of dynein ATPase activity. Neither m74-1 nor
orthovanadate has any obvious affect on GVBD or aster formation. We propose that
dynein function is required for the association of chromosomes with astral
microtubules during in vitro meiosis I spindle assembly in these lysate-extract
mixtures. However, we conclude that dynein function is not required for
centrosome assembly and maturation or for centrosome-dependent aster formation.
PMID- 10194410
TI - nimO, an Aspergillus gene related to budding yeast Dbf4, is required for DNA
synthesis and mitotic checkpoint control.
AB - The nimO predicted protein of Aspergillus nidulans is related structurally and
functionally to Dbf4p, the regulatory subunit of Cdc7p kinase in budding yeast.
nimOp and Dbf4p are most similar in their C-termini, which contain a PEST motif
and a novel, short-looped Cys2-His2 zinc finger-like motif. DNA labelling and
reciprocal shift assays using ts-lethal nimO18 mutants showed that nimO is
required for initiation of DNA synthesis and for efficient progression through S
phase. nimO18 mutants abrogated a cell cycle checkpoint linking S and M phases by
segregating their unreplicated chromatin. This checkpoint defect did not
interfere with other checkpoints monitoring spindle assembly and DNA damage
(dimer lesions), but did prevent activation of a DNA replication checkpoint. The
division of unreplicated chromatin was accelerated in cells lacking a component
of the anaphase-promoting complex (bimEAPC1), consistent with the involvement of
nimO and APC/C in separate checkpoint pathways. A nimO deletion conferred DNA
synthesis and checkpoint defects similar to nimO18. Inducible nimO alleles
lacking as many as 244 C-terminal amino acids supported hyphal growth, but not
asexual development, when overexpressed in a ts-lethal nimO18 strain. However,
the truncated alleles could not rescue a nimO deletion, indicating that the C
terminus is essential and suggesting some type of interaction among nimO
polypeptides.
PMID- 10194411
TI - New actin mutants allow further characterization of the nucleotide binding cleft
and drug binding sites.
AB - We have generated 9 site-specific mutations in Saccharomyces cerevisiae actin.
These mutants display a variety of phenotypes when expressed in vivo, including
slow actin filament turnover, slow fluid-phase endocytosis, and defects in actin
organization. Actin mutation D157E confers resistance to the actin-sequestering
drug, latrunculin A. Latrunculin A inhibits nucleotide exchange on wild-type
yeast actin but not on D157E actin, suggesting that this residue is part of the
latrunculin A binding site. We have refined our earlier map of the phalloidin
binding site on actin, demonstrating a requirement for residue G158 in addition
to D179 and R177. The nine new actin mutants as well as a large collection of
existing actin mutants were also used to identify the putative binding site of
another actin binding drug, tolytoxin, on actin. The actin alleles that result in
decreased sensitivity to this drug cluster at a site near the nucleotide-binding
pocket. Actin purified from one of these mutants has a reduced affinity for
tolytoxin. In addition, tolytoxin causes a 2.4-fold increase in the t1/2 of ATP
exchange, further suggesting that this drug binds near the nucleotide-binding
pocket of actin. We note that the binding sites for latrunculin A, phalloidin,
and tolytoxin all map close to the actin nucleotide binding pocket.
PMID- 10194412
TI - A switch in the cellular localization of macrophage migration inhibitory factor
in the rat testis after ethane dimethane sulfonate treatment.
AB - Macrophage migration inhibitory factor (MIF), one of the first cytokines to be
discovered, has recently been localized to the Leydig cells in adult rat testes.
In the following study, the response of MIF to Leydig cell ablation by the Leydig
cell-specific toxin ethane dimethane sulfonate (EDS) was examined in adult male
rats. Testicular MIF mRNA and protein in testicular interstitial fluid measured
by ELISA and western blot were only marginally reduced by EDS treatment, in spite
of the fact that the Leydig cells were completely destroyed within 7 days.
Immunohistochemistry using an affinity-purified anti-mouse MIF antibody localized
MIF exclusively to the Leydig cells in control testes. At 7 days post-EDS
treatment, there were no MIF immunopositive Leydig cells in the interstitium,
although distinct MIF immunostaining was observed in the seminiferous tubules,
principally in Sertoli cells and residual cytoplasm, and some spermatogonia. A
few peritubular and perivascular cells were also labelled at this time, which
possibly represented mesenchymal Leydig cell precursors. At 14 and 21 days,
Sertoli cell MIF immunoreactivity was observed in only a few tubule cross
sections, while some peritubular and perivascular mesenchymal cells and the re
populating immature Leydig cells were intensely labeled. At 28 days after EDS
treatment, the MIF immunostaining pattern was identical to that of untreated and
control testes. The switch in the compartmentalization of MIF protein at 7 days
after EDS-treatment was confirmed by western blot analysis of interstitial tissue
and seminiferous tubules separated by mechanical dissection. These data establish
that Leydig cell-depleted testes continue to produce MIF, and suggest the
existence of a mechanism of compensatory cytokine production involving the
Sertoli cells. This represents the first demonstration of a hitherto unsuspected
pattern of cellular interaction between the Leydig cells and the seminiferous
tubules which is consistent with an essential role for MIF in male testicular
function.
PMID- 10194413
TI - Mutational analysis of cysteine-string protein function in insulin exocytosis.
AB - Cysteine-string proteins (Csps) are vesicle proteins involved in
neurotransmission. They contain at least four domains: an N-terminal J-domain
which can interact with the chaperone Hsc70, an adjacent linker region, the
defining cysteine rich domain and a variable C terminus. As the relevance of
these domains for the function of Csps in exocytosis is unknown, we have
performed a mutational analysis of Csp domains using insulin release by large
dense core vesicles (LDCVs) as a model of regulated exocytosis. All mutants were
apparently palmitoylated and their subcellular distribution was similar to
endogenous Csp. Point mutations within the highly conserved HPD motif of the J
domain abolished activation of Hsc70. However, these mutations altered the effect
of Csp on exocytosis only after additional truncation of the extreme C terminus
as found in the Csp splice variant Csp2. Furthermore, the strikingly conserved
linker region adjacent to the J-domain was important for Csp function in
exocytosis, but not for the activation of Hsc70 ATPase. The effects of Csp wild
type or mutants were preserved in permeabilized cells excluding an effect on
transmembrane ion fluxes. These observations demonstrate a functional difference
between the two isoforms and suggest a role for the J-domain co-chaperone
function as well as for the newly defined linker region in LDCV exocytosis.
PMID- 10194414
TI - HP33: hepatocellular carcinoma-enriched 33-kDa protein with similarity to
mitochondrial N-acyltransferase but localized in a microtubule-dependent manner
at the centrosome.
AB - Using a new subtraction method and chemically induced rat hepatocellular
carcinomas, we identified a hepatocellular carcinogenesis and hepatocyte
proliferation-related gene designated hp33 that encoded a 33-kDa protein. The
predicted protein was similar to the bovine aralkyl N-acyltransferase and
arylacetyl N-acyltransferase. HP33 was restrictively expressed in the liver and
kidney, and its gene expression was stimulated in the regenerating liver as well
as in hepatocellular carcinoma. Interestingly, it was demonstrated in various
hepatic cells that HP33 was localized in regions surrounding the centrosome,
where mitochondria were not concentrated. Moreover, its centrosomal localization
was evident in the interphase but not in the mitotic phase of the cell cycle. The
centrosomal localization of HP33 was dependent on microtubules, and ectopically
expressed HP33 was seen at centrosomes even in fibroblasts, which do not exhibit
a typical staining pattern of HP33. The centrosomal localization of HP33 became
invisible by nocodazole treatment, whereas the mitochondrial staining pattern was
not affected by it. In vitro cosedimentation experiments using purified
microtubules indicated that HP33 bound to MTs directly and that its MT-binding
ability was dependent on the C-terminal basic domain of the protein. These
results suggest that, different from early predictions based on its primary
structure, HP33 has a growth- and carcinogenesis-related function that may be
independent of mitochondrial function.
PMID- 10194415
TI - Activation of pp60(src) is critical for stretch-induced orienting response in
fibroblasts.
AB - When subjected to uni-axial cyclic stretch (120% in length, 1 Hz), fibroblasts
(3Y1) aligned perpendicular to the stretch axis in a couple of hours.
Concomitantly with this orienting response, protein tyrosine phosphorylation of
cellular proteins (molecular masses of approximately 70 kDa and 120-130 kDa)
increased and peaked at 30 minutes. Immuno-precipitation experiments revealed
that paxillin, pp125(FAK), and pp130(CAS) were included in the 70 kDa, and 120
130 kDa bands, respectively. Treatment of the cells with herbimycin A, a tyrosine
kinase inhibitor, suppressed the stretch induced tyrosine phosphorylation and the
orienting response suggesting that certain tyrosine kinases are activated by
stretch. We focused on pp60(src), the most abundant tyrosine kinase in
fibroblasts. The kinase activity of pp60(src) increased and peaked at 20 minutes
after the onset of cyclic stretch. Treatment of the cells with an anti-sense S
oligodeoxynucleotide (S-ODN) against pp60(src), but not the sense S-ODN,
inhibited the stretch induced tyrosine phosphorylation and the orienting
response. To further confirm the involvement of pp60(src), we performed the same
sets of experiments using c-src-transformed 3Y1 (c-src-3Y1) fibroblasts. Cyclic
stretch induced a similar orienting response in c-src-3Y1 to that in wild-type
3Y1, but with a significantly faster rate. The time course of the stretch-induced
tyrosine phosphorylation was also much faster in c-src-3Y1 than in 3Y1
fibroblasts. These results strongly suggest that cyclic stretch induces the
activation of pp60(src) and that pp60(src) is indispensable for the tyrosine
phosphorylation of pp130(CAS), pp125(FAK) and paxillin followed by the orienting
response in 3Y1 fibroblasts.
PMID- 10194416
TI - NH4+-induced down-regulation of the Saccharomyces cerevisiae Gap1p permease
involves its ubiquitination with lysine-63-linked chains.
AB - Addition of ammonium ions to yeast cells growing on proline as the sole nitrogen
source induces internalization of the general amino acid permease Gap1p and its
subsequent degradation in the vacuole. An essential step in this down-regulation
is Gap1p ubiquitination through a process requiring the Npi1p/Rsp5p ubiquitin
ligase. We show in this report that NPI2, a second gene required for NH4+-induced
down-regulation of Gap1p, codes for the ubiquitin hydrolase Doa4p/Ubp4p/Ssv7p and
that NH4+-induced Gap1p ubiquitination is strongly reduced in npi2 cells. The
npi2 mutation results in substitution of an aromatic amino acid located in a 33
residue sequence shared by some ubiquitin hydrolases of the Ubp family. In this
mutant, as in doa4(delta) cells, the amount of free monomeric ubiquitin is at
least four times lower than in wild-type cells. Both ubiquitination and down
regulation of the permease can be restored in npi2 cells by over-expression of
ubiquitin. In proline-grown wild-type and npi2/doa4 cells overproducing
ubiquitin, Gap1p appears to be mono-ubiquitinated at two lysine acceptor sites.
Addition of NH4+ triggers rapid poly-ubiquitination of Gap1p, the poly-ubiquitin
chains being specifically formed by linkage through the lysine 63 residue of
ubiquitin. Gap1p is thus ubiquitinated differently from the proteins targeted by
ubiquitination for proteolysis by the proteasome, but in the same manner as the
uracil permease, also subject to ubiquitin-dependent endocytosis. When poly
ubiquitination through Lys63 is blocked, the Gap1p permease still undergoes NH4+
induced down-regulation, but to a lesser extent.
PMID- 10194417
TI - RA regulation of keratin expression and myogenesis suggests different ways of
regenerating muscle in adult amphibian limbs.
AB - Formation of a regeneration blastema following limb amputation is believed to
occur through a process of dedifferentiation. It has been suggested, however,
that the cells contributed to the blastema by the stump muscle are satellite-like
cells, rather than cells originated by dedifferentiation. We have previously
shown that simple epithelial keratins 8 and 18 are expressed in the mesenchymal
progenitor cells of the regenerating amphibian limb and in cultured cells with
myogenic potential, and that their expression appears to be causally related to
changes in proliferation and differentiation. We show here that retinoic acid
(RA) affects the expression of these keratins differently in myogenic cells
originated from normal limb and limb blastema. Furthermore, we find that the
effects of RA on proliferation, myogenic differentiation and adhesion of these
cells also differ. In fact, whereas RA does not affect keratin expression,
proliferation or myogenic differentiation in blastemal cells, it does decrease
keratin levels and thymidine incorporation and increase myogenesis in cells from
normal limb. Conversely, RA increases cell adhesion only in blastemal cells.
Significantly, these effects of RA on cultured cells are consistent with those
observed in vivo. Overall the results presented here suggest that in the urodele
limb there are two distinct cell populations with myogenic potential, one
originating from dedifferentiation and one equivalent to the satellite cells of
the mammalian muscle, which are likely to be primarily involved in blastema
formation and muscle repair, respectively.
PMID- 10194418
TI - Glutathione S-conjugate transport in hepatocytes entering the cell cycle is
preserved by a switch in expression from the apical MRP2 to the basolateral MRP1
transporting protein.
AB - The multidrug resistance protein MRP1 and its isoform MRP2 are involved in ATP
dependent glutathione S-conjugate transport and have similar substrate
specificities. MRP2 mediates hepatic organic anion transport into bile. The
physiological function of MRP1 in hepatocytes is unknown. Previous results show
that MRP1 expression is low in quiescent hepatocytes but increased after SV40
large T antigen immortalization, suggesting a relationship with cell
proliferation. Therefore, we determined mrp1 and mrp2 expression in rat
hepatocytes in relation to the cell cycle. By varying cell density we obtained
cultures that are mainly in G1 (high density) or have progressed into the S-phase
or beyond (low density). In both cultures mrp1 mRNA and protein levels are
increased, concomitantly with the disappearance of mrp2. This switch from mrp2 to
mrp1 occurs in the G1 phase of the cell cycle and is associated with a decreased
cell polarity. Mrp1 is located on lateral membranes or on intracellular vesicles,
depending on whether cell-cell contact is established. In both locations mrp1
contributes to cellular glutathione S-conjugate efflux and protects against
oxidative stress-inducing quinones. We conclude that a switch in expression from
the apically located mrp2 to the basolaterally located mrp1 preserves glutathione
S-conjugate transport in hepatocytes entering the cell cycle and protects against
certain cytotoxic agents.
PMID- 10194419
TI - Influence of transforming growth factor beta1 (TGF-beta1) on the behaviour of
porcine thyroid epithelial cells in primary culture through thrombospondin-1
synthesis.
AB - Transforming growth factor beta1 (TGF-beta1) is a secreted polypeptide that is
thought to play a major role in the regulation of folliculogenesis and
differentiation of thyroid cells. On porcine thyroid follicular cells cultured on
plastic substratum, TGF-beta1, in a concentration-dependent way, promoted the
disruption of follicles, cell spreading, migration and confluency by a mechanism
that did not involve cell proliferation. TGF-beta1 strongly activated the
production of thrombospondin-1 and (alpha)vbeta3 integrin in a concentration
dependent manner whereas the expression of thyroglobulin was unaffected.
Anisomycin, an inhibitor of protein synthesis, inhibited the effect of TGF-beta1
on cell organization. Thrombospondin-1 reproduced the effect of TGF-beta1. In the
presence of thrombospondin-1 cells did not organize in follicle-like structures
but, in contrast, spreaded and reached confluency independently of cell
proliferation. This effect is suppressed by an RGD-containing peptide. The
adhesive properties of thrombospondin-1 for thyroid cells were shown to be
mediated by both the amino-terminal heparin-binding domain and the RGD domain of
thrombospondin-1. Adhesion was shown to involve (alpha)vbeta3 integrin. The
results show that TGF-beta1 exerted an influence upon function and behaviour of
follicle cells partly mediated by the synthesis of thrombospondin-1 and of its
receptor (alpha)vbeta3 integrin.
PMID- 10194420
TI - Notch as a mediator of cell fate determination in hematopoiesis: evidence and
speculation.
PMID- 10194421
TI - Association of the platelet glycoprotein Ia C807T gene polymorphism with nonfatal
myocardial infarction in younger patients.
AB - Recently, we have shown that two alleles of the glycoprotein (GP) Ia gene,
designated C807 and T807, are associated with low or high platelet GPIa-IIa
density and consequently with slower or faster rate of platelet adhesion to type
I collagen, respectively. This polymorphism could therefore present a genetic
predisposition for the development of thrombotic disease and hemostasis. We
investigated the relationship of the GPIa C807T dimorphism to the risk of
coronary artery disease (CAD) and myocardial infarction (MI). An allele-specific
polymerase chain reaction (PCR) was developed for genotyping of C807T
polymorphism. DNA samples from 2237 male patients who underwent coronary
angiography on account of coronary heart disease as verified illness or
presumptive diagnosis were genotyped. The odds ratio was calculated as an
estimate of the relative risk by multiple logistic regression. We found a strong
association between the T allele and nonfatal MI among individuals younger than
the mean age of 62 years (n = 1,057; odds ratio, 1.57; P =.004). The odds ratio
of MI increased for T807 carriers with decreasing age. The highest odds ratio was
detected within the youngest 10% of the study sample (<49 years; n = 223; odds
ratio, 2. 61; P =.009). In contrast, no evidence of an association between C807T
dimorphism with CAD was found. Our findings suggest that inherited platelet GP
variations might have an important impact on acute thrombotic disease.
PMID- 10194422
TI - A CD4-independent interaction of human immunodeficiency virus-1 gp120 with CXCR4
induces their cointernalization, cell signaling, and T-cell chemotaxis.
AB - The gp120 envelope glycoprotein of human immunodeficiency virus-1 (HIV-1)
interacts with the CXCR4 chemokine receptor, but it is not known whether gp120
activates CXCR4-mediated signaling cascades in the same manner as its natural
ligand, SDF1alpha. We assessed the effects of wild-type gp120 and a mutant gp120
that interacts with CXCR4 but not CD4 on CD4(-)/CXCR4(+) cells and
CD4(+)/CXCR4(+) cells, respectively. Under both experimental conditions, the
interaction of CXCR4 and gp120 resulted in their CD4-independent
cointernalization. Both molecules were translocated into early endosomes, whereas
neither protein could be detected in late endosomes. Binding of gp120 to CXCR4
resulted in a CD4-independent phosphorylation of Pyk2 and an induction of
chemotactic activity, demonstrating that this interaction has functional
consequences. Interestingly, however, whereas SDF1alpha activated the ERK/MAP
kinase pathway, this cascade was not induced by gp120. Together, these results
suggest that the pathology of HIV-1 infection may be modulated by the distinct
signal transduction pathway mediated by gp120 upon its interaction with CXCR4.
PMID- 10194423
TI - Differential chemokine expression in tissues involved by Hodgkin's disease:
direct correlation of eotaxin expression and tissue eosinophilia.
AB - Hodgkin's disease (HD) is a lymphoid malignancy characterized by infrequent
malignant cells surrounded by abundant inflammatory cells. In this study, we
examined the potential contribution of chemokines to inflammatory cell
recruitment in different subtypes of HD. Chemokines are small proteins that are
active as chemoattractants and regulators of cell activation. We found that HD
tissues generally express higher levels of interferon-gamma-inducible protein-10
(IP-10), Mig, RANTES, macrophage inflammatory protein-1alpha (MIP-1alpha), and
eotaxin, but not macrophage-derived chemotactic factor (MDC), than tissues from
lymphoid hyperplasia (LH). Within HD subtypes, expression of IP-10 and Mig was
highest in the mixed cellularity (MC) subtype, whereas expression of eotaxin and
MDC was highest in the nodular sclerosis (NS) subtype. A significant direct
correlation was detected between evidence of Epstein-Barr virus (EBV) infection
in the neoplastic cells and levels of expression of IP-10, RANTES, and MIP
1alpha. Levels of eotaxin expression correlated directly with the extent of
tissue eosinophilia. By immunohistochemistry, IP-10, Mig, and eotaxin proteins
localized in the malignant Reed-Sternberg (RS) cells and their variants, and to
some surrounding inflammatory cells. Eotaxin was also detected in fibroblasts and
smooth muscle cells of vessels. These results provide evidence of high level
chemokine expression in HD tissues and suggest that chemokines may play an
important role in the recruitment of inflammatory cell infiltrates into tissues
involved by HD.
PMID- 10194424
TI - Filgrastim for cladribine-induced neutropenic fever in patients with hairy cell
leukemia.
AB - Cladribine treatment of hairy cell leukemia (HCL) is complicated by neutropenic
fever in 42% of patients despite documented infections being relatively uncommon.
We performed a study of priming filgrastim followed by cladribine and then
filgrastim again to determine if filgrastim would lead to a reduction of
neutropenia and febrile episodes. Thirty-five patients received filgrastim and
cladribine and were compared with 105 historic controls treated with cladribine
alone. Cladribine was administered at 0.1 mg/kg/d by continuous infusion for 7
days. Filgrastim was administered at 5 micrograms/kg/d subcutaneously on days -3,
-2, and -1 and then again after the completion of cladribine until the absolute
neutrophil count (ANC) was >/=2 x 10(9)/L on 2 consecutive days (days +8, +9,
etc). After filgrastim priming, the median ANC increased from 0.9 x 10(9)/L to
2.26 x 10(9)/L (2.5-fold increase), and after cladribine, the median nadir ANC in
the filgrastim-treated group was 0.53 x 10(9)/L compared with 0.29 x 10(9)/L
among historic controls (P =. 04). The median number of days to an ANC greater
than 1.0 x 10(9)/L was 9 days in the filgrastim-treated group versus 22 days
among historic controls (P < 10(-5)). The percentage of febrile patients, number
of febrile days, and frequency of admissions for antibiotics were not
statistically different in the two groups. Filgrastim regularly increases the ANC
in patients with HCL and shortens the duration of severe neutropenia after
cladribine. This phase II study, with comparison to historical controls, failed
to detect any clinical advantage from the use of filgrastim and cladribine in the
treatment of HCL. Accordingly, the routine adjunctive use of filgrastim with
cladribine in the treatment of HCL cannot be recommended.
PMID- 10194425
TI - Randomized phase II study of fludarabine + cytosine arabinoside + idarubicin +/-
all-trans retinoic acid +/- granulocyte colony-stimulating factor in poor
prognosis newly diagnosed acute myeloid leukemia and myelodysplastic syndrome.
AB - Preclinical data suggest that retinoids, eg, all-trans retinoic acid (ATRA),
lower concentrations of antiapoptotic proteins such as bcl-2, possibly thereby
improving the outcome of anti-acute myeloid leukemia (AML) chemotherapy.
Granulocyte colony-stimulating factor (G-CSF) has been considered to be
potentially synergistic with ATRA in this regard. Accordingly, we randomized 215
patients with newly diagnosed AML (153 patients) or high-risk myelodysplastic
syndrome (MDS) (refractory anemia with excess blasts [RAEB] or RAEB-t, 62
patients) to receive fludarabine + ara-C + idarubicin (FAI) alone, FAI + ATRA,
FAI + G-CSF, or FAI + ATRA + G-CSF. Eligibility required one of the following:
age over 71 years, a history of abnormal blood counts before M.D. Anderson (MDA)
presentation, secondary AML/MDS, failure to respond to one prior course of
chemotherapy given outside MDA, or abnormal renal or hepatic function. For the
two treatment arms containing ATRA, ATRA was given 2 days (day-2) before
beginning and continued for 3 days after completion of FAI. For the two treatment
arms including G-CSF, G-CSF began on day-1 and continued until neutrophil
recovery. Patients with white blood cell (WBC) counts >50,000/microL began ATRA
on day 1 and G-CSF on day 2. Events (death, failure to achieve complete remission
[CR], or relapse from CR) have occurred in 77% of the 215 patients. Reflecting
the poor prognosis of the patients entered, the CR rate was only 51%, median
event-free survival (EFS) time once in CR was 36 weeks, and median survival time
was 28 weeks. A Cox regression analysis indicated that, after accounting for
patient prognostic variables, none of the three adjuvant treatment combinations
(FAI + ATRA, FAI + G, FAI + ATRA + G) affected survival, EFS, or EFS once in CR
compared with FAI. Similarly, there were no significant effects of either ATRA
ignoring G-CSF, or of G-CSF ignoring ATRA. As previously found, a diagnosis of
RAEB or RAEB-t rather than AML was insignificant. There were no indications that
the effect of ATRA differed according to cytogenetic group, diagnosis (AML or
MDS), or treatment schedule. Logistic regression analysis indicated that, after
accounting for prognosis, addition of G-CSF +/- ATRA to FAI improved CR rate
versus either FAI or FAI + ATRA, but G-CSF had no effect on the other outcomes.
We conclude that addition of ATRA +/- G-CSF to FAI had no effect on CR rate,
survival, EFS, or EFS in CR in poor prognosis, newly diagnosed AML or high-risk
MDS.
PMID- 10194426
TI - TT virus in bone marrow transplant recipients.
AB - TT virus (TTV) is a newly discovered transfusion-transmissible DNA virus, which
may cause posttransfusion hepatitis. The virus was detected in 12% of Japanese
blood donors. The aim of the study is to investigate the prevalence and clinical
influence of TTV in bone marrow transplant (BMT) recipients. Sera from 25 BMT
recipients obtained 6 to 12 weeks after the transplant were examined for TTV-DNA
by the seminested polymerase chain reaction. Serial samples were additionally
analyzed in patients with TTV-DNA. Fifteen of 25 recipients (60%) were positive
for TTV-DNA after transplant, whereas it was detected in only two of 20 BMT
donors (10%). In patients positive for TTV-DNA before BMT, the amount of TTV-DNA
decreased to an undetectable level during the myelosuppressed period after BMT.
We also found that there was a novel group of TTV, G3, classified by the
nucleotide sequences. The median peak alanine aminotransferase (ALT) levels were
135.0 IU/L and 116.5 IU/L (normal range, 4 to 36 IU/L) in TTV-positive and TTV
negative recipients, respectively. In one of the seven TTV-positive patients who
developed hepatic injury (ALT > 150 IU/L), a serial change in the serum TTV titer
showed a good correlation with the ALT level. We concluded that (1) the
prevalence of TTV is high in BMT recipients, (2) TTV might be replicated mainly
in hematopoietic cells, (3) transfusion-transmitted TTV may cause persistent
infection, (4) a novel genetic group of TTV, G3, was discovered, and (5) TTV does
not seem to frequently cause hepatic injury, although one patient was strongly
suggested to have TTV-induced hepatitis.
PMID- 10194427
TI - A randomized phase 3 study of peripheral blood progenitor cell mobilization with
stem cell factor and filgrastim in high-risk breast cancer patients.
AB - This randomized study compared the number of leukaphereses required to collect an
optimal target yield of 5 x 10(6) CD34(+) peripheral blood progenitor cells/kg,
using either stem cell factor (SCF) at 20 micrograms/kg/d in combination with
Filgrastim at 10 micrograms/kg/d or Filgrastim alone at 10 micrograms/kg/d, from
203 patients with high-risk stage II, III, or IV breast cancer. Leukapheresis
began on day 5 of cytokine administration and continued daily until the target
yield of CD34(+) cells had been reached or a maximum of 5 leukaphereses
performed. By day 5 of leukapheresis, 63% of the patients treated with SCF plus
Filgrastim (n = 100) compared with 47% of those receiving Filgrastim alone (n =
103) reached the CD34(+) cell target yield. There was a clinically and
statistically significant reduction (P <.05) in the number of leukaphereses
required to reach the target yield for the patients receiving SCF plus Filgrastim
(median, 4 leukaphereses) compared with patients receiving Filgrastim alone
(median, 6 or more leukapherses; ie, <50% of patients reached the target in 5
leukaphereses). All patients receiving SCF were premedicated with antihistamines,
albuterol, and pseudoephedrine. Treatment was safe, generally well tolerated, and
not associated with life-threatening or fatal toxicity. In conclusion, SCF plus
Filgrastim is a more effective peripheral blood progenitor cell (PBPC)
mobilization regimen than Filgrastim alone. In addition to the potential for
reduced leukapheresis-related morbidity and costs, SCF offers additional options
for obtaining cells for further graft manipulation.
PMID- 10194428
TI - HFE mutations analysis in 711 hemochromatosis probands: evidence for S65C
implication in mild form of hemochromatosis.
AB - Hereditary hemochromatosis (HH) is a common autosomal recessive genetic disorder
of iron metabolism. The HFE candidate gene encoding an HLA class I-like protein
involved in HH was identified in 1996. Two missense mutations have been
described: C282Y, accounting for 80% to 90% of HH chromosomes, and H63D, which is
associated with a milder form of the disease representing 40% to 70% of non-C282Y
HH chromosomes. We report here on the analysis of C282Y, H63D, and the 193A-->T
substitution leading to the S65C missense substitution in a large series of
probands and controls. The results confirm that the C282Y substitution was the
main mutation involved in hemochromatosis, accounting for 85% of carrier
chromosomes, whereas the H63D substitution represented 39% of the HH chromosomes
that did not carry the C282Y mutation. In addition, our screening showed that the
S65C substitution was significantly enriched in probands with at least one
chromosome without an assigned mutation. This substitution accounted for 7.8% of
HH chromosomes that were neither C282Y nor H63D. This enrichment of S65C among HH
chromosomes suggests that the S65C substitution is associated with the mild form
of hemochromatosis.
PMID- 10194429
TI - Neutrophil activation and hemostatic changes in healthy donors receiving
granulocyte colony-stimulating factor.
AB - Granulocyte colony-stimulating factor (G-CSF) enhances neutrophil functions in
vitro and in vivo. It is known that neutrophil-derived products can alter the
hemostatic balance. To understand whether polymorphonuclear leukocyte (PMN)
activation, measured as PMN degranulation and phenotypical change, may be
associated to hemostatic alterations in vivo, we have studied the effect of
recombinant human G-CSF (rHuG-CSF) administration on leukocyte parameters and
hemostatic variables in healthy donors of hematopoietic progenitor cells (HPCs).
Twenty-six consecutive healthy donors receiving 10 micrograms/kg/d rHuG-CSF
subcutaneously for 5 to 7 days to mobilize HPCs for allogeneic transplants were
included in the study. All of them responded to rHuG-CSF with a significant white
blood cell count increase. Blood samples were drawn before therapy on days 2 and
5 and 1 week after stopping rHuG-CSF treatment. The following parameters were
evaluated: (1) PMN activation parameters, ie, surface CD11b/CD18 antigen
expression, plasma elastase antigen levels and cellular elastase activity; (2)
plasma markers of endothelium activation, ie, thrombomodulin (TM) and von
Willebrand factor (vWF) antigens; (3) plasma markers of blood coagulation
activation, ie, F1+2, TAT complex, D-dimer; and (4) mononuclear cell (MNC)
procoagulant activity (PCA) expression. The results show that, after starting
rHuG-CSF, an in vivo PMN activation occurred, as demonstrated by the significant
increment of surface CD11b/CD18 and plasma elastase antigen levels. Moreover, PMN
cellular elastase activity, which was significantly increased at 1 day of
treatment, returned to baseline at day 5 to 6, in correspondence with the
elastase antigen peak in the circulation. This change was accompanied by a
parallel significant increase in plasma levels of the two endothelial and the
three coagulation markers. The PCA generated in vitro by unstimulated MNC
isolated from rHuG-CSF-treated subjects was not different from that of control
cells from untreated subjects. However, endotoxin-stimulated MNC isolated from on
treatment individuals produced significantly more PCA compared with both baseline
and control samples. All of the parameters were decreased or normal 1 week after
stopping treatment. These data show that rHuG-CSF induces PMN activation and
transiently affects some hemostatic variables in healthy HPC donor subjects. The
clinical significance of these findings remains to be established.
PMID- 10194430
TI - Tissue uptake of circulating thrombopoietin is increased in immune-mediated
compared with irradiated thrombocytopenic mice.
AB - We have previously demonstrated a significant inverse correlation between
circulating thrombopoietin (TPO) levels and peripheral platelet (PLT) counts in
patients with thrombocytopenia secondary to megakaryocytic hypoplasia but not in
patients with immune thrombocytopenic purpura (ITP; Chang et al, Blood 88:3354,
1996). To test the hypothesis that the differences in the circulating TPO levels
in these two types of thrombocytopenia are caused by differences in the total
capacity of Mpl receptor-mediated TPO clearance, thrombocytopenia was induced in
female CD-1 mice either by sublethal irradiation (irradiated) or rabbit antimouse
PLT serum (RAMPS) for 1 day (1 d RAMPS) and 5 days (5 d RAMPS). A well
characterized murine model of autoimmune thrombocytopenic purpura, male (NZW x
BXSB) F1 mice (W/B F1), was also included in this study. All thrombocytopenic
mice and their controls received trace amounts of 125I-recombinant murine TPO
(125I-rmTPO) intravenously and were killed 3 hours postinjection. Blood cell
associated radioactivity was significantly decreased in all 4 groups of
thrombocytopenic mice. Significantly increased plasma and decreased whole spleen
associated radioactivity was observed in the irradiated group compared with
controls (P <.05). While a lesser but still significant increase in plasma and
decrease in whole spleen-associated radioactivity was observed in the 1 d RAMPS
mice (P <.05), there were no significant differences between the 5 d RAMPS nor
the W/B F1 male mice compared with controls, although whole spleen-associated
radioactivity was higher in the W/B F1 male. A significant inverse correlation of
plasma and whole spleen-associated radioactivity was demonstrated in W/B F1 male
mice (r = -.91, n = 6, P <.05). There was also a decrease in bone (femur)/blood
associated radioactivity in the irradiated group compared with controls (P <.05),
but a significant increase in 1 d and 5 d RAMPS mice (P <.01). Furthermore, the
125I-rmTPO uptake capacity within the spleen and marrow of immune
thrombocytopenic mice appeared to be associated with a higher megakaryocytic mass
when tissue samples were examined by light microscopy. Internalization of 125I
rmTPO by megakaryocytes and PLTs in the spleens and marrows of ITP mice was also
demonstrated directly using electron microscopic autoradiography. Labeled PLTs
were also found within splenic macrophages. Additionally, the mean PLT volumes of
RAMPS mice were significantly higher than those of the control and irradiated
mice (P <.05), as was the bound 125I-rmTPO (cpm) per million PLT (P <.05).
Finally, significantly decreased 125I-rmTPO degradation products were only found
in the plasma of the irradiated mice compared with control animals (P <.05).
These data suggest that the lack of Mpl+ cells in the mice with thrombocytopenia
secondary to megakaryocytic hypoplasia (irradiated) results in decreased uptake
and degradation of TPO and higher circulating TPO levels. Furthermore, these data
also suggest that, after a brief TPO surge in response to immune thrombocytopenia
(1 d RAMPS), the lack of an inverse correlation of circulating TPO with PLT
counts during steady-state immune thrombocytopenic mice (5 d RAMPS + W/B F1 male)
is due, at least in part, to its uptake and degradation by the high PLT turnover
and increased mass of megakaryocytes.
PMID- 10194431
TI - Soluble interleukin-6 (IL-6) receptor with IL-6 stimulates megakaryopoiesis from
human CD34(+) cells through glycoprotein (gp)130 signaling.
AB - We have recently shown that stimulation of glycoprotein (gp) 130, the membrane
anchored signal transducing receptor component of IL-6, by a complex of human
soluble interleukin-6 receptor (sIL-6R) and IL-6 (sIL-6R/IL-6), potently
stimulates the ex vivo expansion as well as erythropoiesis of human
stem/progenitor cells in the presence of stem cell factor (SCF). Here we show
that sIL-6R dose-dependently enhanced the generation of megakaryocytes (Mks)
(IIbIIIa-positive cells) from human CD34(+) cells in serum-free suspension
culture supplemented with IL-6 and SCF. The sIL-6R/IL-6 complex also
synergistically acted with IL-3 and thrombopoietin (TPO) on the generation of Mks
from CD34(+) cells, whereas the synergy of IL-6 alone with TPO was barely
detectable. Accordingly, the addition of sIL-6R to the combination of SCF + IL-6
also supported a substantial number of Mk colonies from CD34(+) cells in serum
free methylcellulose culture, whereas SCF + IL-6 in the absence of sIL-6R rarely
induced Mk colonies. The addition of monoclonal antibodies against gp130 to the
suspension and clonal cultures completely abrogated the megakaryopoiesis induced
by sIL-6R/IL-6 in the presence of SCF, whereas an anti-TPO antibody did not,
indicating that the observed megakaryopoiesis by sIL-6R/IL-6 is a response to
gp130 signaling and independent of TPO. Furthermore, human CD34(+) cells were
subfractionated into two populations of IL-6R-negative (CD34(+) IL-6R-) and IL-6R
positive (CD34(+) IL-6R+) cells by fluorescence-activated cell sorting. The
CD34(+) IL-6R- cells produced a number of Mks as well as Mk colonies in cultures
supplemented with sIL-6R/IL-6 or TPO in the presence of SCF. In contrast, CD34(+)
IL-6R+ cells generated much less Mks and lacked Mk colony forming activity under
the same conditions. Collectively, the present results indicate that most of the
human Mk progenitors do not express IL-6R, and that sIL-6R confers the
responsiveness of human Mk progenitors to IL-6. Together with the presence of
functional sIL-6R in human serum and relative unresponsiveness of human Mk
progenitors to IL-6 in vitro, current results suggest that the role of IL-6 may
be mainly mediated by sIL-6R, and that the gp130 signaling initiated by the sIL
6R/ IL-6 complex is involved in human megakaryopoiesis in vivo.
PMID- 10194432
TI - Characterization of bone marrow laminins and identification of alpha5-containing
laminins as adhesive proteins for multipotent hematopoietic FDCP-Mix cells.
AB - Laminins are extracellular matrix glycoproteins that influence the phenotype and
functions of many types of cells. Laminins are heterotrimers composed of alpha,
beta, and gamma polypeptides. So far five alpha, three beta, and two gamma
polypeptide chains, and 11 variants of laminins have been proposed. Laminins
interact in vitro with mature blood cells and malignant hematopoietic cells. Most
studies have been performed with laminin-1 (alpha1beta1gamma1), and its
expression in bone marrow is unclear. Employing an antiserum reacting with most
laminin isoforms, we found laminins widely expressed in mouse bone marrow.
However, no laminin alpha1 chain but rather laminin alpha2, alpha4, and alpha5
polypeptides were found in bone marrow. Our data suggest presence of laminin-2
(alpha2beta1gamma1), laminin-8 (alpha4beta1gamma1), and laminin-10
(alpha5beta1gamma1) in bone marrow. Northern blot analysis showed expression of
laminin alpha1, alpha2, alpha4, and alpha5 chains in long-term bone marrow
cultures, indicating upregulation of laminin alpha1 chain expression in vitro.
Laminins containing alpha5 chain, in contrast to laminin-1, were strongly
adhesive for multipotent hematopoietic FDCP-mix cells. Integrin alpha6 and beta1
chains mediated this adhesion, as shown by antibody perturbation experiments. Our
findings indicate that laminins other than laminin-1 are functional in adhesive
interactions in bone marrow.
PMID- 10194433
TI - Functional expression of the high affinity receptor for IgE (FcepsilonRI) in
human platelets and its' intracellular expression in human megakaryocytes.
AB - The high affinity IgE receptor (FcepsilonRI) expressed on the cell surface of
mast cells and basophils is the key molecule in triggering the IgE-mediated
allergic reaction. Recently, it was elucidated that the FcepsilonRI is expressed
on a variety of other cells like Langerhans cells, monocytes, and eosinophils,
and the functional importance of the FcepsilonRI expression in Langerhans cells
was also shown. Some studies suggest that human platelets may play important
roles in allergic inflammation through the cell-surface expression of the
FcepsilonRII and FcgammaRII. Here, we report that human platelets and
megakaryocytes constitutively express the messenger RNA and protein for the
FcepsilonRI. Although the FcepsilonRI is expressed on the cell surface of human
platelets, it is only detected in the cytoplasm of human megakaryocytes. We also
confirmed that human platelets express the genes for the alpha, beta, and gamma
chains of the FcepsilonRI without any defined mutations. Furthermore, stimulation
of human platelets via the FcepsilonRI induced the release of serotonin and
RANTES (Regulated on Activation, Normal T Expressed, and presumably Secreted).
Taken together, these results suggest a novel and important role for human
platelets in perpetuating allergic inflammation through the expression of and
activation via the FcepsilonRI.
PMID- 10194434
TI - Cleavage of factor V at Arg 506 by activated protein C and the expression of
anticoagulant activity of factor V.
AB - Activated protein C (APC) inhibits coagulation by cleaving and inactivating
procoagulant factor Va (FVa) and factor VIIIa (FVIIIa). FV, in addition to being
the precursor of FVa, has anticoagulant properties; functioning in synergy with
protein S as a cofactor of APC in the inhibition of the FVIIIa-factor IXa (FIXa)
complex. FV:Q506 isolated from an individual homozygous for APC-resistance is
less efficient as an APC-cofactor than normal FV (FV:R506). To investigate the
importance of the three APC cleavage sites in FV (Arg-306, Arg-506, and Arg-679)
for expression of its APC-cofactor activity, four recombinant FV mutants
(FV:Q306, FV:Q306/Q506, FV:Q506, and FV:Q679) were tested. FV mutants with Gln
(Q) at position 506 instead of Arg (R) were found to be poor APC-cofactors,
whereas Arg to Gln mutations at positions 306 or 679 had no negative effect on
the APC-cofactor activity of FV. The loss of APC-cofactor activity as a result of
the Arg-506 to Gln mutation suggested that APC-cleavage at Arg-506 in FV is
important for the ability of FV to function as an APC-cofactor. Using Western
blotting, it was shown that both wild-type FV and mutant FV was cleaved by APC
during the FVIIIa inhibition. At optimum concentrations of wild-type FV (11
nmol/L) and protein S (100 nmol/L), FVIIIa was found to be highly sensitive to
APC with maximum inhibition occurring at less than 1 nmol/L APC. FV:Q506 was
inactive as an APC-cofactor at APC-concentrations = 1 nmol/L and only partially
active at higher APC concentrations. Our results show that increased expression
of FV anticoagulant activity correlates with APC-mediated cleavage at Arg-506 in
FV, but not with cleavage at Arg-306 nor at Arg-679.
PMID- 10194435
TI - A mutation in the extracellular cysteine-rich repeat region of the beta3 subunit
activates integrins alphaIIbbeta3 and alphaVbeta3.
AB - Inside-out signaling regulates the ligand-binding function of integrins through
changes in receptor affinity and/or avidity. For example, alphaIIbbeta3 is in a
low-affinity/avidity state in resting platelets, and activation of the receptor
by platelet agonists enables fibrinogen to bind. In addition, certain mutations
and truncations of the integrin cytoplasmic tails are associated with a high
affinity/avidity receptor. To further evaluate the structural basis of integrin
activation, stable Chinese hamster ovary (CHO) cell transfectants were screened
for high-affinity/avidity variants of alphaIIbbeta3. One clone (AM-1) expressed
constitutively active alphaIIbbeta3, as evidenced by (1) binding of soluble
fibrinogen and PAC1, a ligand-mimetic antialphaIIbbeta3 antibody; and (2)
fibrinogen-dependent cell aggregation. Sequence analysis and mutant expression in
293 cells proved that a single amino acid substitution in the cysteine-rich,
extracellular portion of beta3(T562N) was responsible for receptor activation. In
fact, T562N also activated alphaVbeta3, leading to spontaneous binding of soluble
fibrinogen to 293 cells. In contrast, neither T562A nor T562Q activated
alphaIIbbeta3, suggesting that acquisition of asparagine at residue 562 was the
relevant variable. T562N also led to aberrant glycosylation of beta3, but this
was not responsible for the receptor activation. The binding of soluble
fibrinogen to alphaIIbbeta3(T562N) was not sufficient to trigger tyrosine
phosphorylation of pp125(FAK), indicating that additional post-ligand binding
events are required to activate this protein tyrosine kinase during integrin
signaling. These studies have uncovered a novel gain-of-function mutation in a
region of beta3 intermediate between the ligand-binding region and the
cytoplasmic tail, and they suggest that this region is involved in integrin
structural changes during inside-out signaling.
PMID- 10194436
TI - Optimal proliferation of a hematopoietic progenitor cell line requires either
costimulation with stem cell factor or increase of receptor expression that can
be replaced by overexpression of Bcl-2.
AB - In vitro proliferation of hematopoietic stem cells requires costimulation by
multiple regulatory factors whereas expansion of lineage-committed progenitor
cells generated by stem cells usually requires only a single factor. The distinct
requirement of factors for proliferation coincides with the differential temporal
expression of the subunits of cytokine receptors during early stem cell
differentiation. In this study, we explored the underlying mechanism of the
requirement of costimulation in a hematopoietic progenitor cell line TF-1. We
found that granulocyte-macrophage colony-stimulating factor (GM-CSF) optimally
activated proliferation of TF-1 cells regardless of the presence or absence of
stem cell factor (SCF). However, interleukin-5 (IL-5) alone sustained survival of
TF-1 cells and required costimulation of SCF for optimal proliferation. The
synergistic effect of SCF was partly due to its anti-apoptosis activity.
Overexpression of the IL-5 receptor alpha subunit (IL5Ralpha) in TF-1 cells by
genetic selection or retroviral infection also resumed optimal proliferation due
to correction of the defect in apoptosis suppression. Exogenous expression of an
oncogenic anti-apoptosis protein, Bcl-2, conferred on TF-1 cells an IL-5
dependent phenotype. In summary, our data suggested SCF costimulation is only
necessary when the expression level of IL5Ralpha is low and apoptosis suppression
is defective in the signal transduction of IL-5. Expression of Bcl-2 proteins
released the growth restriction of the progenitor cells and may be implicated in
leukemia formation.
PMID- 10194437
TI - Erythropoietin induces the tyrosine phosphorylation of GAB1 and its association
with SHC, SHP2, SHIP, and phosphatidylinositol 3-kinase.
AB - Five tyrosine-phosphorylated proteins with molecular masses of 180, 145, 116,
100, and 70 kD are associated with phosphatidylinositol 3-kinase (PI 3-kinase) in
erythropoietin (Epo)-stimulated UT-7 cells. The 180- and 70-kD proteins have been
previously shown to be IRS2 and the Epo receptor. In this report, we show that
the 116-kD protein is the IRS2-related molecular adapter, GAB1. Indeed, Epo
induced the transient tyrosine phosphorylation of GAB1 in UT-7 cells. Both
kinetics and Epo dose-response experiments showed that GAB1 tyrosine
phosphorylation was a direct consequence of Epo receptor activation. After
tyrosine phosphorylation, GAB1 associated with the PI 3-kinase, the
phosphotyrosine phosphatase SHP2, the phosphatidylinositol 3,4,5 trisphosphate 5
phosphatase SHIP, and the molecular adapter SHC. GAB1 was also associated with
the molecular adapter GRB2 in unstimulated cells, and this association
dramatically increased after Epo stimulation. Thus, GAB1 could be a scaffold
protein able to couple the Epo receptor activation with the stimulation of
several intracellular signaling pathways. Epo-induced tyrosine phosphorylation of
GAB1 was also observed in normal human erythroid progenitors isolated from cord
blood. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and
thrombopoietin (TPO) also induced the tyrosine phosphorylation of GAB1 in UT-7
cells, indicating that this molecule participates in the signal transduction of
several cytokine receptors.
PMID- 10194438
TI - Stromal cell CD9 regulates differentiation of hematopoietic stem/progenitor
cells.
AB - CD9 belongs to the transmembrane 4 superfamily, and has been shown to influence
cell proliferation, motility, and adhesion. We show here that ligation of CD9
modifies proliferation and/or differentiation of hematopoietic stem/progenitors.
Pluripotent EML-C1 hematopoietic cells were cocultured with MS-5 stromal cells in
the presence of KMC8.8, an anti-CD9 antibody. Numbers of recovered EML-C1 cells
were slightly reduced and the antibody caused the hematopoietic cells to migrate
beneath the adherent stromal cell layer. Of particular interest, EML-C1 cells
recovered from CD9-ligated cultures had undifferentiated properties. Separate
pretreatment of the two cell types with antibody showed that stromal-cell CD9
mediated these responses. Spontaneous expression of erythroid marker was
completely blocked and there was a shift towards undifferentiated clonogenic
progenitors. Immunoprecipitation studies showed that stromal-cell CD9 associates
with the beta1 subunit of integrin, as well as a novel 100 kD protein. Antibody
cross-linking of cell surface CD9 increased the amount of 100 kD protein that was
subsequently coprecipitated with CD9. These observations show that stromal-cell
CD9 influences physical interactions with hematopoietic cells and may be one
factor that determines the degree of stem cell differentiation.
PMID- 10194439
TI - Mechanism of flt3 ligand expression in bone marrow failure: translocation from
intracellular stores to the surface of T lymphocytes after chemotherapy-induced
suppression of hematopoiesis.
AB - The flt3 ligand (FL) is a growth factor for primitive hematopoietic cells. Serum
levels of FL are inversely related to the number and proliferative capacity of
early hematopoietic progenitors. We sought to elucidate the molecular mechanism
underlying this regulation. Expression of FL was examined in peripheral blood
(PB) and bone marrow (BM) cells under normal steady-state hematopoiesis and
during transient BM failure induced by chemoradiotherapy in 16 patients with
hematological malignancies. Using anti-FL antibodies in Western analysis, flow
cytometry, and confocal microscopy, we detected high levels of preformed FL
inside but not on the surface of T lymphocytes in steady-state hematopoiesis.
Intracellular FL colocalized with giantin and ERGIC-53, indicating that it is
stored within and close to the Golgi apparatus. After chemotherapy-induced
hematopoietic failure, FL rapidly translocated to the surface of T lymphocytes
and the levels of FL released to serum increased approximately 100-fold.
Expression of FL mRNA was enhanced only about sevenfold; a similar, twofold to
sixfold increase in mRNA was observed in the thymus and BM of mice with
irradiation-induced aplasia. Upregulation of FL mRNA was delayed when compared
with the appearance of cell surface-associated and soluble protein isoforms. The
described changes in FL expression in response to chemotherapy-induced aplasia
were observed in all patients, irrespective of the diagnosis and treatment
regimen. Our data demonstrate that mobilization of preformed FL from
intracellular stores rather than de novo synthesis is responsible for increased
FL levels in BM failure.
PMID- 10194440
TI - Identification and characterization of endothelial glycoprotein Ib using viper
venom proteins modulating cell adhesion.
AB - The expression and function of a glycoprotein Ib (GPIb) complex on human
umbilical vein endothelial cells (HUVECs) is still a matter of controversy. We
characterized HUVEC GPIb using viper venom proteins: alboaggregins A and B,
echicetin, botrocetin, and echistatin. Echicetin is an antagonist, and
alboaggregins act as agonists of the platelet GPIb complex. Botrocetin is a venom
protein that alters von Willebrand factor (vWF) conformation and increases its
binding affinity for the GPIb complex. Echistatin is a disintegrin that blocks
alphavbeta3. Echistatin, but not echicetin, inhibited the adhesion to vWF of
Chinese hamster ovary (CHO) cells transfected with alphavbeta3. We found the
following: (1) Binding of monoclonal antibodies against GPIbalpha to HUVECs was
moderately increased after stimulation with cytokines and phorbol ester.
Echicetin demonstrated an inhibitory effect. (2) Both echicetin and echistatin,
an alphavbeta3 antagonist, inhibited the adhesion of HUVECs to immobilized vWF in
a dose-dependent manner. The inhibitory effect was additive when both proteins
were used together. (3) Botrocetin potentiated the adhesion of HUVECs to vWF, and
this effect was completely abolished by echicetin, but not by echistatin. (4) CHO
cells expressing GPIbalphabeta/IX adhered to vWF (in the presence of botrocetin)
and to alboaggregins; GPIbalpha was required for this reaction. Echicetin, but
not echistatin, inhibited the adhesion of cells transfected with GPIbalphabeta/IX
to immobilized vWF. (5) HUVECs adhered strongly to immobilized vWF and
alboaggregins with extensive spreading, which was inhibited by LJ1b1, a
monoclonal antibody against GPIb. The purified alphavbeta3 receptor did not
interact with the alboaggregins, thereby excluding the contribution of
alphavbeta3 in inducing HUVEC spreading on alboaggregins. In conclusion, our data
confirm the presence of a functional GPIb complex expressed on HUVECs in low
density. This complex may mediate HUVEC adhesion and spreading on immobilized vWF
and alboaggregins.
PMID- 10194441
TI - Human platelets contain SNARE proteins and a Sec1p homologue that interacts with
syntaxin 4 and is phosphorylated after thrombin activation: implications for
platelet secretion.
AB - In response to thrombin and other extracellular activators, platelets secrete
molecules from large intracellular vesicles (granules) to initiate thrombosis.
Little is known about the molecular machinery responsible for vesicle docking and
secretion in platelets and the linkage of that machinery to cell activation. We
found that platelet membranes contain a full complement of interacting proteins
VAMP, SNAP-25, and syntaxin 4-that are necessary for vesicle docking and fusion
with the plasma membrane. Platelets also contain an uncharacterized homologue of
the Sec1p family that appears to regulate vesicle docking through its binding
with a cognate syntaxin. This platelet Sec1 protein (PSP) bound to syntaxin 4 and
thereby excluded the binding of SNAP-25 with syntaxin 4, an interaction critical
to vesicle docking. As predicted by its sequence, PSP was detected predominantly
in the platelet cytosol and was phosphorylated in vitro by protein kinase C
(PKC), a secretion-linked kinase, incorporating 0.87 +/- 0.11 mol of PO4 per mole
of protein. PSP was also specifically phosphorylated in permeabilized platelets
after cellular stimulation by phorbol esters or thrombin and this phosphorylation
was blocked by the PKC inhibitor Ro-31-8220. Phosphorylation by PKC in vitro
inhibited PSP from binding to syntaxin 4. Taken together, these studies indicate
that platelets, like neurons and other cells capable of regulated secretion,
contain a unique complement of interacting vesicle docking proteins and PSP, a
putative regulator of vesicle docking. The PKC-dependent phosphorylation of PSP
in activated platelets and its inhibitory effects on syntaxin 4 binding provide a
novel functional link that may be important in coupling the processes of cell
activation, intracellular signaling, and secretion.
PMID- 10194442
TI - Human erythropoietin induces a pro-angiogenic phenotype in cultured endothelial
cells and stimulates neovascularization in vivo.
AB - Hematopoietic and endothelial cell lineages share common progenitors.
Accordingly, cytokines formerly thought to be specific for the hematopoietic
system have been shown to affect several functions in endothelial cells,
including angiogenesis. In this study, we investigated the angiogenic potential
of erythropoietin (Epo), the main hormone regulating proliferation,
differentiation, and survival of erythroid cells. Epo receptors (EpoRs) have been
identified in the human EA.hy926 endothelial cell line by Western blot analysis.
Also, recombinant human Epo (rHuEpo) stimulates Janus Kinase-2 (JAK-2)
phosphorylation, cell proliferation, and matrix metalloproteinase-2 (MMP-2)
production in EA.hy926 cells and significantly enhances their differentiation
into vascular structures when seeded on Matrigel. In vivo, rHuEpo induces a
potent angiogenic response in the chick embryo chorioallantoic membrane (CAM).
Accordingly, endothelial cells of the CAM vasculature express EpoRs, as shown by
immunostaining with an anti-EpoR antibody. The angiogenic response of CAM blood
vessels to rHuEpo was comparable to that elicited by the prototypic angiogenic
cytokine basic fibroblast growth factor (FGF2), it occurred in the absence of a
significant mononuclear cell infiltrate, and it was not mimicked by endothelin-1
(ET-1) treatment. Taken together, these data demonstrate the ability of Epo to
interact directly with endothelial cells and to elicit an angiogenic response in
vitro and in vivo and thus act as a bona fide direct angiogenic factor.
PMID- 10194443
TI - Regulation of the megakaryocytic glycoprotein IX promoter by the oncogenic Ets
transcription factor Fli-1.
AB - Glycoprotein (GP) IX is a subunit of the von Willebrand receptor, GPIb-V-IX,
which mediates adhesion of platelets to the subendothelium of damaged blood
vessels. Previous characterization of the GPIX promoter identified a functional
Ets site that, when disrupted, reduced promoter activity. However, the Ets
protein(s) that regulated GPIX promoter expression was unknown. In this study,
transient cotransfection of several GPIX promoter/reporter constructs into 293T
kidney fibroblasts with a Fli-1 expression vector shows that the oncogenic
protein Fli-1 can transactivate the GPIX promoter when an intact GPIX Ets site is
present. In addition, Fli-1 binding of the GPIX Ets site was identified in
antibody supershift experiments in nuclear extracts derived from hematopoietic
human erythroleukemia cells. Comparative studies showed that Fli-1 was also able
to transactivate the GPIbalpha and, to a lesser extent, the GPIIb promoter.
Immunoblot analysis identified Fli-1 protein in lysates derived from platelets.
In addition, expression of Fli-1 was identified immunohistochemically in
megakaryocytes derived from CD34(+) cells treated with the megakaryocyte
differentiation and proliferation factor, thrombopoietin. These results suggest
that Fli-1 is likely to regulate lineage-specific genes during
megakaryocytopoiesis.
PMID- 10194444
TI - Genetic and pharmacological analyses of Syk function in alphaIIbbeta3 signaling
in platelets.
AB - Agonists induce inside-out alphaIIbbeta3 signaling resulting in fibrinogen
binding and platelet aggregation. These in turn trigger outside-in signaling
resulting in further platelet stimulation. Because the Syk tyrosine kinase is
activated during both phases of integrin signaling, we evaluated its role in
alphaIIbbeta3 function in murine platelets rendered null for Syk by gene
targeting and in human platelets incubated with piceatannol, a tyrosine kinase
inhibitor reportedly selective for Syk. Both Syk null murine platelets and
piceatannol-treated human platelets exhibited a partial, but statistically
significant defect in activation of alphaIIbbeta3 by adenine diphosphate (ADP) +/
epinephrine as assessed by fibrinogen binding. Syk null platelets adhered
normally to immobilized fibrinogen, and mice with these platelets exhibited
normal tail bleeding times. In contrast, piceatannol treatment of human platelets
completely inhibited platelet adhesion to immobilized fibrinogen. The discrepancy
in extent of integrin dysfunction between murine and human platelet models may be
due to lack of specificity of piceatannol, because this compound inhibited the
activity of Src and FAK as well as Syk and also reduced tyrosine phosphorylation
of multiple platelet proteins. These results provide genetic evidence that Syk
plays a role in alphaIIbbeta3 signaling in platelets and pharmacological evidence
that, although piceatannol also inhibits alphaIIbbeta3 signaling, it does so by
inhibtion of multiple protein tyrosine kinases.
PMID- 10194445
TI - Immunization with recombinant human granulocyte-macrophage colony-stimulating
factor as a vaccine adjuvant elicits both a cellular and humoral response to
recombinant human granulocyte-macrophage colony-stimulating factor.
AB - Granulocyte-macrophage colony-stimulating factor (GM-CSF) is an important
cytokine for the generation and propagation of antigen-presenting cells and for
priming a cellular immune response. We report here that use of recombinant human
GM-CSF (rhGM-CSF), administered as an adjuvant in a peptide-based vaccine trial
given monthly by intradermal injection, led to the development of a T-cell and
antibody response to rhGM-CSF. An antibody response occurred in the majority of
patients (72%). This antibody response was not found to be neutralizing. In
addition, by 48-hour delayed type hypersensitivity (DTH) skin testing, 17% of
patients were shown to have a cellular immune response to the adjuvant rhGM-CSF
alone. Thymidine incorporation assays also showed a peripheral blood T-cell
response to rhGM-CSF in at least 17% of the patients. The generation of rhGM-CSF
specific T-cell immune responses, elicited in this fashion, is an important
observation because rhGM-CSF is being used as a vaccine adjuvant in various
vaccine strategies. rhGM-CSF-specific immune responses may be incorrectly
interpreted as antigen-specific immunity, particularly when local DTH responses
to vaccination are the primary means of immunologic evaluation. We found no
evidence of hematologic or infectious complications as a result of the
development of rhGM-CSF-specific immune responses.
PMID- 10194446
TI - Functional Fas expression in human thymic epithelial cells.
AB - Fas, a cell surface receptor, can induce apoptosis after cross-linking with its
ligand. We report that Fas antigen is constitutively expressed in medullary
epithelial cells of the human thymus. Expression is decreased in cultured thymic
epithelial cells (TEC), similarly to HLA-DR antigen. TEC are resistant to anti
Fas-induced apoptosis after 4 days of primary culture, and this resistance is
reversed by concomitant addition of cycloheximide. Cycloheximide also
downregulated the expression of Fas-associated phosphatase-1, which has been
found to inhibit Fas-induced apoptosis. This phosphatase could be involved in the
resistance to Fas-induced apoptosis observed on day 4 of TEC culture. When TEC
were subcultured after 10 to 13 days of primary culture, exposure to interleukin
1-beta, tumor necrosis factor-alpha, and interferon-gamma, alone or together,
reinduced Fas mRNA and protein expression. In coculture with activated
thymocytes, TEC also upregulated Fas protein expression. Cytokine-activated TEC
became sensitive to apoptosis induced by an agonistic anti-Fas antibody. This
apoptosis was inhibited by Z-VAD-fmk but not by Z-DEVD-fmk and DEVDase activity
was slightly increased in Fas-stimulated TEC, suggesting that DEVDase activity is
not sufficient to induce TEC apoptosis. Taken together, these data show that the
Fas receptor is expressed in medullary epithelial cells of the human thymus and
is able to induce apoptosis.
PMID- 10194447
TI - Increased BAX expression is associated with an increased risk of relapse in
childhood acute lymphocytic leukemia.
AB - Studies in cell lines have indicated that expression of the BCL-2 family of
proteins is an important determinant of chemotherapy-induced apoptosis; however,
the level of expression of these proteins in childhood acute lymphoblastic
leukemia (ALL) has not been extensively reported. Using quantitative Western
blotting we have determined the level of expression of BCL-2, BAX, MCL-1, and BCL
X in lymphoblasts from 47 children with ALL (33 at presentation only, 4 at
relapse only, and 10 at both presentation and on relapse). Results were
determined as a ratio to actin as an internal control. BCL-2, BAX, and MCL-1 were
detected in all samples. BCL-XL was only detected in 6 cases (4 at presentation
and 2 at relapse) and BCL-XS in none. No correlation was found between expression
and white blood cell count, age at diagnosis, gender, or blast karyotype. BCL-2
levels and the BCL/BAX and MCL-1/BAX ratios were found to be significantly higher
in B-lineage as compared with T-lineage disease (P <.003,.02, and.02,
respectively). No consistent pattern of change in expression was noted in the 10
cases studied at both presentation and relapse. Kaplan-Meier analysis showed a
significant correlation between high BAX expression and an increased probability
of relapse (P <.05 by the log rank test), suggesting that chemosensitivity in
leukemic blasts may be regulated by factors that override the BCL-2 pathway.
PMID- 10194448
TI - Molecular analysis of single B cells from T-cell-rich B-cell lymphoma shows the
derivation of the tumor cells from mutating germinal center B cells and
exemplifies means by which immunoglobulin genes are modified in germinal center B
cells.
AB - T-cell-rich B-cell lymphoma (TCRBCL) belongs to the group of diffuse large cell
lymphomas (DLL). It is characterized by a small number of tumor B cells among a
major population of nonmalignant polyclonal T cells. To identify the
developmental stage of the tumor progenitor cells, we micromanipulated the
putative neoplastic large CD20(+) cells from TCRBCLs and amplified and sequenced
immunoglobulin (Ig) V gene rearrangements from individual cells. In six cases,
clonal Ig heavy, as well as light chain, gene rearrangements were amplified from
the isolated B cells. All six cases harbored somatically mutated V gene
rearrangements with an average mutation frequency of 15.5% for heavy (VH) and
5.9% for light (VL) chains and intraclonal diversity based on somatic mutation.
These findings identify germinal center (GC) B cells as the precursors of the
transformed B cells in TCRBCL. The study also exemplifies various means how Ig
gene rearrangements can be modified by GC B cells or their malignant counterparts
in TCRBCL: In one case, the tumor precursor may have switched from kappa to
lambda light chain expression after acquiring a crippling mutation within the
initially functional kappa light chain gene. In another case, the tumor cells
harbor two in-frame VH gene rearrangements, one of which was rendered
nonfunctional by somatic mutation. Either the tumor cell precursor entered the GC
with two potentially functional in-frame rearrangements or the second VHDHJH
rearrangement occurred in the GC after the initial in-frame rearrangement was
inactivated by somatic mutation. Finally, in each of the six cases, at least one
cell contained two (or more) copies of a clonal Ig gene rearrangement with
sequence variations between these copies. The presence of sequence variants for V
region genes within single B cells has so far not been observed in any other
normal or transformed B lymphocyte. Fluorescence in situ hybridization (FISH)
points to a generalized polyploidy of the tumor cells.
PMID- 10194449
TI - Adverse effects of activated cytotoxic T lymphocytes on the clinical outcome of
nodal anaplastic large cell lymphoma.
AB - Systemic (nodal) anaplastic large cell lymphoma (ALCL) is a subgroup of T-cell
non-Hodgkin's lymphomas with a relatively favorable clinical outcome. Part of
systemic ALCLs harbor a genetic aberration (usually the t(2;5)(p23;q35)
translocation) containing the anaplastic lymphoma kinase (ALK) gene at 2p23,
which results in aberrant expression of the ALK protein. Recently, we have shown
that the presence of high percentages of activated cytotoxic T lymphocytes (CTLs)
in tumor biopsy specimens of Hodgkin's disease (HD) is associated with a poor
prognosis. In the present study, we investigated the prognostic value of
percentages of activated CTLs in combination with ALK expression in primary nodal
ALCL. Primary nodal biopsies of 42 patients with ALCL were investigated for the
percentage of activated CTLs (quantified using Q-PRODIT) and the expression of
ALK by immunohistochemistry using monoclonal antibodies (MoAbs) directed against
T-cell antigen granzyme B (GrB) and ALK, respectively. These parameters were
evaluated for their predictive value regarding progression-free and overall
survival time. The presence of a high percentage of activated CTLs (ie, >/=15%)
was found to be an unfavorable prognostic marker. In combination with a lack of
ALK expression, it was possible to identify a group of patients with a very poor
prognosis. In this group, 13 of 16 patients died within 2 years as a result of
the disease. Of the remaining 26 patients, only three (all ALK negative) died (P
<.0001). Furthermore, the percentage of activated CTLs combined with ALK status
appeared to be of stronger prognostic value than the International Prognostic
Index (IPI). We conclude that a high percentage of activated CTLs present in
biopsy material of patients with primary nodal ALCL is a strong indicator for an
unfavorable clinical outcome. The combination of ALK expression and percentage of
activated CTLs appears to be more sensitive than the IPI in identifying a group
of patients with a highly unfavorable clinical outcome who may be eligible for
alternative (high dose) therapy schemes.
PMID- 10194450
TI - ALK+ lymphoma: clinico-pathological findings and outcome.
AB - A distinct pathologic entity (ALK+ lymphoma) that is characterized by expression
of the anaplastic lymphoma kinase (ALK) protein has recently emerged within the
heterogeneous group of CD30(+) anaplastic large-cell lymphomas. Information on
clinical findings and treatment outcome of ALK+ lymphoma is still limited, and no
data are available concerning the value of the International Prognostic Index
when applied to this homogeneous disease entity. To clarify these issues, a
recently developed monoclonal antibody ALKc (directed against the cytoplasmic
portion of ALK) was used to detect expression of the ALK protein in paraffin
embedded biopsies from 96 primary, systemic T/null anaplastic large-cell
lymphomas, and the ALK staining pattern was correlated with morphological
features, clinical findings, risk factors (as defined by the International
Prognostic Index), and outcome in 78 patients (53 ALK+ and 25 ALK-). Strong
cytoplasmic and/or nuclear ALK positivity was detected in 58 of 96 ALCL cases
(60.4%), and it was associated with a morphological spectrum (common type, 82.7%;
giant cell, 3.5%; lymphohistiocytic, 8. 6%; and small cell, 5.2%) that reflected
the ratio of large anaplastic elements (usually showing cytoplasmic and nuclear
ALK positivity) to small neoplastic cells (usually characterized by nucleus
restricted ALK expression). Clinically, ALK+ lymphoma mostly occurred in children
and young adults (mean age, 22.01 +/- 10.87 years) with a male predominance
(male/female [M/F] ratio, 3.0) that was particularly striking in the second-third
decades of life (M/F ratio, 6.5) and usually presented as an aggressive, stage
III-IV disease, frequently associated with systemic symptoms (75%) and extranodal
involvement (60%), especially skin (21%), bone (17%), and soft tissues (17%). As
compared with ALK+ lymphoma, ALK- cases occurred in older individuals (mean age,
43.33 +/- 16.15 years) and showed a lower M/F ratio (0.9) as well as lower
incidence of stage III-IV disease and extranodal involvement at presentation.
Overall survival of ALK+ lymphoma was far better than that of ALK- anaplastic
large-cell lymphoma (71% +/- 6% v 15% +/- 11%, respectively). However, within the
good prognostic category of ALK+ lymphoma, survival was 94% +/- 5% for the
low/low intermediate risk group (age-adjusted International Prognostic Index, 0
to 1) and 41% +/- 12% for the high/high intermediate risk group (age-adjusted
International Prognostic Index, >/=2). Multivariate analysis identified ALK
expression and the International Prognostic Index as independent variables that
were able to predict survival among T/null primary, systemic anaplastic large
cell lymphoma. Thus, we suggest that such parameters should be taken into
consideration for the design of future clinical trials.
PMID- 10194451
TI - A novel SH2-containing phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase
(SHIP2) is constitutively tyrosine phosphorylated and associated with src
homologous and collagen gene (SHC) in chronic myelogenous leukemia progenitor
cells.
AB - Because of the probable causal relationship between constitutive p210(bcr/abl)
protein tyrosine kinase activity and manifestations of chronic-phase chronic
myelogenous leukemia (CML; myeloid expansion), a key goal is to identify relevant
p210 substrates in primary chronic-phase CML hematopoietic progenitor cells. We
describe here the purification and mass spectrometric identification of a 155-kD
tyrosine phosphorylated protein associated with src homologous and collagen gene
(SHC) from p210(bcr/abl)-expressing hematopoietic cells as SHIP2, a recently
reported, unique SH2-domain-containing protein closely related to
phosphatidylinositol polyphosphate 5-phosphatase SHIP. In addition to an N
terminal SH2 domain and a central catalytic region, SHIP2 (like SHIP1) possesses
both potential PTB(NPXY) and SH3 domain (PXXP) binding motifs. Thus, two unique 5
ptases with striking structural homology are coexpressed in hematopoietic
progenitor cells. Stimulation of human hematopoietic growth factor responsive
cell lines with stem cell factor (SCF), interleukin-3 (IL-3), and granulocyte
macrophage colony-stimulating factor (GM-CSF) demonstrate the rapid tyrosine
phosphorylation of SHIP2 and its resulting association with SHC. This finding
suggests that SHIP2, like that reported for SHIP1 previously, is linked to
downstream signaling events after activation of hematopoietic growth factor
receptors. However, using antibodies specific to these two proteins, we
demonstrate that, whereas SHIP1 and SHIP2 selectively hydrolyze PtdIns(3,4,5)P3
in vitro, only SHIP1 hydrolyzes soluble Ins(1,3,4,5)P4. Such an enzymatic
difference raises the possibility that SHIP1 and SHIP2 may serve different
functions. Preliminary binding studies using lysates from p210(bcr/abl)
expressing cells indicate that both Ptyr SHIP2 and Ptyr SHIP1 bind to the PTB
domain of SHC but not to its SH2 domain. Interestingly, SHIP2 was found to
selectively bind to the SH3 domain of ABL, whereas SHIP1 selectively binds to the
SH3 domain of Src. Furthermore, in contrast to SHIP1, SHIP2 did not bind to
either the N-terminal or C-terminal SH3 domains of GRB2. These observations
suggest (1) that SHIP1 and SHIP2 may have a different hierarchy of binding SH3
containing proteins and therefore may modulate different signaling pathways
and/or localize to different cellular compartments and (2) that they may be
substrates for tyrosine phosphorylation by different tyrosine kinases. Because
recent evidence has clearly implicated both PI(3,4, 5)P3 and PI(3,4)P2 in growth
factor-mediated signaling, our finding that both SHIP1 and SHIP2 are
constitutively tyrosine phosphorylated in CML primary hematopoietic progenitor
cells may thus have important implications in p210(bcr/abl)-mediated myeloid
expansion.
PMID- 10194452
TI - Induced differentiation of U937 cells by 1,25-dihydroxyvitamin D3 involves cell
cycle arrest in G1 that is preceded by a transient proliferative burst and an
increase in cyclin expression.
AB - The hormonal form of vitamin D, 1,25-dihydroxyvitamin D3 [1, 25(OH)2D3], is a
potent inhibitor of cellular proliferation as well as an inducer of
differentiation of myeloid leukemic cells to macrophages. We have previously
reported that a number of genes are upregulated by 1,25(OH)2D3 during myeloid
differentiation, including the cyclin-dependent kinase (CDK) inhibitors p21, p27,
15, and p18, suggesting that cell cycle arrest and differentiation are tightly
linked processes. We further explore here the relationship between growth
inhibition and differentiation. We report that, upon 1, 25(OH)2D3 treatment, U937
cells exhibited an early proliferative burst followed by growth inhibition and
subsequent differentiation. Although CDK levels remain constant throughout, this
transient increase in proliferation was accompanied by increases in cyclin A, D1,
and E protein levels. p21 and p27 levels were also elevated during both the
proliferative burst and subsequent inhibition of cell growth. Ectopic
overexpression of p21 and/or p27 in U937 cells, in the absence of hormone,
resulted in an induction of the expression of monocyte/macrophage-specific
markers, whereas overexpression of p15 and p18 had no effect, suggesting that a
subset of CDK inhibitors are important for both growth arrest and differentiation
and that an early increase in proliferation is somehow a prerequisite for
subsequent differentiation. However, no such biphasic behavior was detected in
cells that are growth inhibited by 1,25(OH)2D3 but do not differentiate, such as
MCF-7 cells. Taken together, these results indicate that both growth stimulation
and subsequent inhibition precede differentiation and involve induction of both
cyclins and p21 and p27, whereas cell cycle arrest of differentiated cells can be
achieved simply by elevations in CDK inhibitors.
PMID- 10194453
TI - The effect of glucocorticoids on the expression of L-selectin on
polymorphonuclear leukocyte.
AB - When active bone marrow release is induced by inflammatory stimuli, it is
associated with an increase in L-selectin expression on circulating
polymorphonuclear leukocyte (PMN). This contrasts sharply with glucocorticoid
induced granulocytosis that is associated with decreased L-selectin expression on
PMN. The present study was designed to determine if the reduced L-selectin
expression observed after glucocorticoid treatment is the result of suppression
of L-selectin synthesis in the bone marrow. New Zealand white rabbits treated
with dexamethasone (2.0 mg/kg, a single dose intravenously) were shown to have
decreased L-selectin expression on circulating PMN 12 to 24 hours after treatment
(P <.01) with a return to baseline levels by 48 hours. When dexamethasone was
administered 48 hours after the bone marrow PMN were pulse labeled with the
thymidine analogue, 5'-bromo-2'-deoxyuridine (BrdU), L-selectin expression on
BrdU-labeled PMN released from the bone marrow was decreased (P <.01).
Dexamethasone decreased L-selectin expression on segmented PMN in the bone marrow
(P <.05) but not on PMN already in the circulation. We conclude that
glucocorticoids decrease L-selectin expression on circulating PMN by
downregulating L-selectin expression in the maturation pool of bone marrow and
speculate that this is an important glucocorticoid effect that influences the
recruitment of PMN into inflammatory sites.
PMID- 10194454
TI - Graft-versus-leukemia effect and graft-versus-host disease can be differentiated
by cytotoxic mechanisms in a murine model of allogeneic bone marrow
transplantation.
AB - Allogeneic bone marrow transplantation (allo-BMT) is associated with both graft
versus-host disease (GVHD) and graft-versus-leukemia (GVL) effect. In the present
study, we examined the contribution of cytotoxic effector mechanisms, which are
mediated by tumor necrosis factor-alpha (TNF-alpha), Fas ligand (FasL), or
perforin, to GVHD and GVL effect in a murine BMT model. Bone marrow cells plus
spleen cells (BMS) from wild-type, FasL-defective, or perforin-deficient donors
were transferred into lethally irradiated recipients in the parent (C57BL/6) to
F1 (C57BL/6 x DBA/2) BMT model with or without prior inoculation of DBA/2
leukemia L1210 or P815 mast cytoma cells. The effect of anti-TNF-alpha antibody
administration was also examined. Whereas the defect or blockade of each
cytotoxic pathway could ameliorate lethal acute GVHD, the GVL effect was
differentially affected. The wild-type BMS recipients died of acute GVHD within
50 days without residual leukemia cells. The FasL-defective BMS recipients showed
60%< survival over 80 days without acute GVHD or residual leukemia cells.
Administration of anti-TNF-alpha antibody resulted in early leukemia relapse and
the recipients died within 25 days with massive leukemia infiltration in the
liver. The perforin-deficient BMS recipients died within 60 days with residual
leukemia cells. These results suggest that blockade of the Fas/FasL pathway could
be used for ameliorating GVHD without impairing GVL effect in allo-BMT.
PMID- 10194455
TI - Clinical Microbiology Reviews: genesis of a journal.
AB - In 1986 planning for a new ASM review journal, Clinical Microbiology Reviews
(CMR), began. CMR would publish articles primarily of interest to persons
concerned with pathogenesis, laboratory diagnosis, epidemiology, and control of
human and veterinary pathogens. The first issue was published in January 1988,
with quarterly publication since then. The journal quickly became successful in
terms of subscribers and impact on the field, earning a strong national and
international reputation. The achievements of CMR are owed to many persons,
including the editorial board, the production team, and especially the
contributing authors.
PMID- 10194457
TI - Chagas' disease and the autoimmunity hypothesis.
AB - The notion that the pathology of Chagas' disease has an autoimmune component was
initially based on the finding of circulating antibodies binding heart tissue
antigens in patients and mice chronically infected with Trypanosoma cruzi. Later,
T lymphocytes reactive with heart or nerve tissue antigens were found in chagasic
mice and patients, extending the concept to include cell-mediated immunity.
However, there is disagreement about whether the observed immunologic
autoreactivities are triggered by T. cruzi epitopes and then affect host tissue
antigens by virtue of molecular mimicry or are elicited by host antigens exposed
to lymphocytes after tissue damage caused by the parasite. There is also
disagreement about the relevance of immunologic autoreactivities to the
pathogenesis of Chagas' disease because of the lack of reproducibility of some
key reports supporting the autoimmunity hypothesis, conflicting data from
independent laboratories, conclusions invalidated by advances in our
understanding of the immunologic mechanisms underlying cell lysis, and, last but
not least, a lack of direct, incontrovertible evidence that cross-reacting
antibodies or autoreactive cells mediate the typical pathologic changes
associated with human Chagas' disease. The data and views backing and questioning
the autoimmunity hypothesis for Chagas' disease are summarized in this review.
PMID- 10194456
TI - Syphilis: review with emphasis on clinical, epidemiologic, and some biologic
features.
AB - Syphilis is a chronic disease with a waxing and waning course, the manifestations
of which have been described for centuries. It occurs worldwide, and the
incidence varies significantly with geographic location. Transmission is mainly
by sexual contact. The causative organism, Treponema pallidum, was first
described in 1905, but because of the inability to culture the organism and the
limitations of direct microscopy, serologic testing is the mainstay of laboratory
diagnosis. The disease has been arbitrarily divided into several stages. The
primary stage is defined by a chancre at the site of inoculation. The secondary
stage is characterized by a polymorphic rash, lymphadenopathy, and other systemic
manifestations. A variable asymptomatic latent period follows, which for
epidemiologic purposes is divided into early (<1 year) and late (>1 year) stages.
The early stages (primary, secondary, and early latent) are potentially
infectious. The tertiary stage is the most destructive and is marked by
cardiovascular and neurologic sequelae and gummatous involvement of any organ
system. Congenital infection may result in protean early or late manifestations.
Unlike many other bacteria causing infectious diseases, the organism remains
sensitive to penicillin, and this remains the mainstay of therapy.
PMID- 10194460
TI - Resistance of human cytomegalovirus to antiviral drugs.
AB - Resistance of cytomegalovirus (CMV) to antiviral agents is a well-recognized
phenomenon that has been observed in the laboratory and in the clinical setting.
Infections caused by antiviral-resistant CMV have been found exclusively among
immunocompromised individuals, including patients with AIDS, bone marrow and
solid-organ transplant recipients, and patients with hematologic malignancies,
and in individuals with primary immunodeficiencies. The majority of these
infections have been described to occur in patients with AIDS receiving prolonged
antiviral therapy for CMV end-organ disease. Antiviral agents currently licensed
for the treatment of CMV infections include ganciclovir, foscarnet, and
cidofovir. Resistance of CMV to ganciclovir is related to mutations in the UL97
region of the viral genome and/or mutations in the viral DNA polymerase.
Resistance to foscarnet and cidofovir is associated with mutations in the viral
DNA polymerase. Antiviral susceptibility of CMV strains containing DNA polymerase
mutations is dependent on the region of the DNA polymerase where the mutations
are located. Some DNA polymerase mutant viruses are cross-resistant to
ganciclovir, foscarnet, and cidofovir. The recognition that specific UL97 and
UL54 mutations are associated with resistance to antiviral agents has led to the
development of molecular methods for detection of mutant viruses. This article
reviews the mechanisms of resistance of CMV to antiviral agents, the laboratory
methods for detection of resistant CMV, and the clinical aspects of infections
caused by antiviral-resistant CMV.
PMID- 10194458
TI - Clinical, microbial, and biochemical aspects of the exfoliative toxins causing
staphylococcal scalded-skin syndrome.
AB - The exfoliative (epidermolytic) toxins of Staphylococcus aureus are the causative
agents of the staphylococcal scalded-skin syndrome (SSSS), a blistering skin
disorder that predominantly affects children. Clinical features of SSSS vary
along a spectrum, ranging from a few localized blisters to generalized
exfoliation covering almost the entire body. The toxins act specifically at the
zona granulosa of the epidermis to produce the characteristic exfoliation,
although the mechanism by which this is achieved is still poorly understood.
Despite the availability of antibiotics, SSSS carries a significant mortality
rate, particularly among neonates with secondary complications of epidermal loss
and among adults with underlying diseases. The aim of this article is to provide
a comprehensive review of the literature spanning more than a century and to
cover all aspects of the disease. The epidemiology, clinical features, potential
complications, risk factors, susceptibility, diagnosis, differential diagnoses,
investigations currently available, treatment options, and preventive measures
are all discussed in detail. Recent crystallographic data on the toxins has
provided us with a clearer and more defined approach to studying the disease.
Understanding their mode of action has important implications in future treatment
and prevention of SSSS and other diseases, and knowledge of their specific site
of action may provide a useful tool for physiologists, dermatologists, and
pharmacologists.
PMID- 10194459
TI - Molecular techniques for detection, species differentiation, and phylogenetic
analysis of microsporidia.
AB - Microsporidia are obligate intracellular protozoan parasites that infect a broad
range of vertebrates and invertebrates. These parasites are now recognized as one
of the most common pathogens in human immunodeficiency virus-infected patients.
For most patients with infectious diseases, microbiological isolation and
identification techniques offer the most rapid and specific determination of the
etiologic agent. This is not a suitable procedure for microsporidia, which are
obligate intracellular parasites requiring cell culture systems for growth.
Therefore, the diagnosis of microsporidiosis currently depends on morphological
demonstration of the organisms themselves. Although the diagnosis of
microsporidiosis and identification of microsporidia by light microscopy have
greatly improved during the last few years, species differentiation by these
techniques is usually impossible and transmission electron microscopy may be
necessary. Immunfluorescent-staining techniques have been developed for species
differentiation of microsporidia, but the antibodies used in these procedures are
available only at research laboratories at present. During the last 10 years, the
detection of infectious disease agents has begun to include the use of nucleic
acid-based technologies. Diagnosis of infection caused by parasitic organisms is
the last field of clinical microbiology to incorporate these techniques and
molecular techniques (e.g., PCR and hybridization assays) have recently been
developed for the detection, species differentiation, and phylogenetic analysis
of microsporidia. In this paper we review human microsporidial infections and
describe and discuss these newly developed molecular techniques.
PMID- 10194461
TI - Respiratory syncytial virus infection: immune response, immunopathogenesis, and
treatment.
AB - Respiratory syncytial virus (RSV) is the single most important cause of lower
respiratory tract infection during infancy and early childhood. Once RSV
infection is established, the host immune response includes the production of
virus-neutralizing antibodies and T-cell-specific immunity. The humoral immune
response normally results in the development of anti-RSV neutralizing-antibody
titers, but these are often suboptimal during an infant's initial infection. Even
when the production of RSV neutralizing antibody following RSV infection is
robust, humoral immunity wanes over time. Reinfection during subsequent seasons
is common. The cellular immune response to RSV infection is also important for
the clearance of virus. This immune response, vital for host defense against RSV,
is also implicated in the immunopathogenesis of severe lower respiratory tract
RSV bronchiolitis. Many details of the immunology and immunopathologic mechanisms
of RSV disease known at present have been learned from rodent models of RSV
disease and are discussed in some detail. In addition, the roles of
immunoglobulin E, histamine, and eosinophils in the immunopathogenesis of RSV
disease are considered. Although the treatment of RSV bronchiolitis is primarily
supportive, the role of ribavirin is briefly discussed. Novel approaches to the
development of new antiviral drugs with promising anti-RSV activity in vitro are
also described.
PMID- 10194464
TI - Recent developments in lymphocyte activation: linking kinases to downstream
signaling events.
PMID- 10194463
TI - Update on diagnosis, management, and prevention of hepatitis B virus infection.
AB - Acute and chronic hepatitis B virus (HBV) infection is a leading cause of liver
disease worldwide. It is estimated that approximately 350 million people
worldwide have chronic HBV infection and that 1 million persons die each year
from HBV-related chronic liver disease. In the past decade, significant progress
in the understanding of the molecular virology and pathogenesis of HBV infection
has been made. In addition, effective treatment modalities have been developed
for persons with chronic infection. Worldwide, prevention of HBV transmission has
become a high priority. In 1992, the Global Advisory Group to the World Health
Organization recommended that all countries integrate hepatitis B vaccine into
national immunization programs by 1997. Currently, 80 countries have done so and
several others are planning to. Many countries have reported dramatic reductions
in the prevalence of chronic HBV infection among children born since the
hepatitis B vaccine was introduced into infant immunization schedules. Recent
reports from Taiwan indicate a reduction in the incidence of liver cancer among
children as a result of widespread hepatitis B vaccination programs.
PMID- 10194466
TI - Patients with preeclampsia develop agonistic autoantibodies against the
angiotensin AT1 receptor.
AB - Immune mechanisms and the renin-angiotensin system are implicated in
preeclampsia. We investigated 25 preeclamptic patients and compared them with 12
normotensive pregnant women and 10 pregnant patients with essential hypertension.
Antibodies were detected by the chronotropic responses to AT1 receptor-mediated
stimulation of cultured neonatal rat cardiomyocytes coupled with receptor
specific antagonists. Immunoglobulin from all preeclamptic patients stimulated
the AT1 receptor, whereas immunoglobulin from controls had no effect. The
increased autoimmune activity decreased after delivery. Affinity-column
purification and anti-human IgG and IgM antibody exposure implicated an IgG
antibody directed at the AT1 receptor. Peptides corresponding to sites on the AT1
receptor's second extracellular loop abolished the stimulatory effect. Western
blotting with purified patient IgG and a commercially obtained AT1 receptor
antibody produced bands of identical molecular weight. Furthermore, confocal
microscopy of vascular smooth muscle cells showed colocalization of purified
patient IgG and AT1 receptor antibody. The protein kinase C (PKC) inhibitor
calphostin C prevented the stimulatory effect. Our results suggest that
preeclamptic patients develop stimulatory autoantibodies against the second
extracellular AT1 receptor loop. The effect appears to be PKC-mediated. These
novel autoantibodies may participate in the angiotensin II-induced vascular
lesions in these patients.
PMID- 10194467
TI - Angiotensin II attenuates renal cortical cyclooxygenase-2 expression.
AB - We have previously shown that in rat renal cortex, cyclooxygenase-2 (COX-2)
expression is localized to cTALH cells in the region of the macula densa, and
that dietary salt restriction increases COX-2 expression. Administration of the
angiotensin converting inhibitor, captopril, further increased COX-2 mRNA and
renal cortical COX-2 immunoreactivity, with the most pronounced expression in the
macula densa. Administration of an AT1 receptor antagonist, losartan, also
significantly increased cortical COX-2 mRNA expression and COX-2
immunoreactivity. Mutant mice homozygous for both Agtr1a and Agtr1b null
mutations (Agtr1a-/-,Agtr1b-/-) demonstrated large increases in immunoreactive
COX-2 expression inthe cTALH/macula densa. To determine whether increased COX
2expression in response to ACE inhibition mediated increases in renin production,
rats were treated with captopril for one week with or without the specific COX-2
inhibitor, SC58236. Plasma renin activity increased significantly in the
captropril group, and this increase was significantly inhibited by simultaneous
treatment with SC58236. Thus, these studies indicated that angiotensin II
inhibitors augment upregulation of renal cortical COX-2 in states of volume
depletion, suggesting that negative feedback by the renin-angiotensin system
modulates renal cortical COX-2 expression and that COX-2 is a mediator of
increased renin production in response to inhibition of angiotension II
production.
PMID- 10194465
TI - Protein-protein interaction in insulin signaling and the molecular mechanisms of
insulin resistance.
PMID- 10194468
TI - Carbon monoxide stimulates the apical 70-pS K+ channel of the rat thick ascending
limb.
AB - We have investigated the expression of heme oxygenase (HO) in the rat kidney and
the effects of HO-dependent heme metabolites on the apical 70-pS K+ channel in
the thick ascending limb (TAL). Reverse transcriptase-PCR (RT-PCR) and Western
blot analyses indicate expression of the constitutive HO form, HO-2, in the rat
cortex and outer medulla. Patch-clamping showed that application of 10 microM
chromium mesoporphyrin (CrMP), an inhibitor of HO, reversibly reduced the
activity of the apical 70-pS K+ channel, defined by NPo, to 26% of the control
value. In contrast, addition of 10 microM magnesium protoporphyrin had no
significant effect on channel activity. HO involvement in regulation of the
apical 70-pS K+ channel of the TAL, was further indicated by the addition of 10
microM heme-L-lysinate, which significantly stimulated the channel activity in
cell-attached patches by 98%. The stimulatory effect of heme on channel activity
was also observed in inside-out patches in the presence of 0.5-1 mM reduced
nicotinamide adenine dinucleotide phosphate. This was completely abolished by 10
microM CrMP, suggesting that a HO-dependent metabolite of heme mediated the
effect. This was further supported by exposure of the cytosolic membrane of
inside-out patches to a carbon monoxide-bubbled bath solution, which increased
channel activity. Moreover, carbon monoxide completely abolished the effect of 10
microM CrMP on the channel activity. In contrast, 10 microM biliverdin, another
HO-dependent metabolite of heme, had no effect. We conclude that carbon monoxide
produced from heme via an HO-dependent metabolic pathway stimulates the apical 70
pS K+ channel in the rat TAL.
PMID- 10194469
TI - Ordering of ceramide formation, caspase activation, and mitochondrial changes
during CD95- and DNA damage-induced apoptosis.
AB - To evaluate the role of ceramide (Cer) in apoptosis signaling, we examined Cer
formation induced by CD95, etoposide, or gamma-radiation (IR) in relation to
caspase activation and mitochondrial changes in Jurkat T cells. The Cer response
to all three stimuli was mapped in between caspases sensitive to
benzoyloxycarbonyl-VAD-fluoromethylketone (zVAD-fmk) and acetyl-DEVD-aldehyde
(DEVD-CHO). Cer production was independent of nuclear fragmentation but
associated with the occurrence of other aspects of the apoptotic morphology.
Caspase-8 inhibition abrogated Cer formation and apoptosis induced by CD95 but
did not affect the response to etoposide or IR, placing CD95-induced Cer
formation downstream from caspase-8 and excluding a role for caspase-8 in the DNA
damage pathways. CD95 signaling to the mitochondria required caspase-8, whereas
cytochrome c release in response to DNA damage was caspase-independent. These
results indicate that the caspases required for the Cer response to etoposide and
IR reside at or downstream from the mitochondria. Bcl-2 overexpression abrogated
the Cer response to etoposide and IR and reduced CD95-induced Cer accumulation.
We conclude that the Cer response to DNA damage fully depends on mitochondrion
dependent caspases, whereas the response to CD95 partially relies on these
caspases. Our data imply that Cer is not instrumental in the activation of
inducer caspases or signaling to the mitochondria. Rather, Cer formation is
associated with the execution phase of apoptosis.
PMID- 10194462
TI - Aspergillus fumigatus and aspergillosis.
AB - Aspergillus fumigatus is one of the most ubiquitous of the airborne saprophytic
fungi. Humans and animals constantly inhale numerous conidia of this fungus. The
conidia are normally eliminated in the immunocompetent host by innate immune
mechanisms, and aspergilloma and allergic bronchopulmonary aspergillosis,
uncommon clinical syndromes, are the only infections observed in such hosts.
Thus, A. fumigatus was considered for years to be a weak pathogen. With increases
in the number of immunosuppressed patients, however, there has been a dramatic
increase in severe and usually fatal invasive aspergillosis, now the most common
mold infection worldwide. In this review, the focus is on the biology of A.
fumigatus and the diseases it causes. Included are discussions of (i) genomic and
molecular characterization of the organism, (ii) clinical and laboratory methods
available for the diagnosis of aspergillosis in immunocompetent and
immunocompromised hosts, (iii) identification of host and fungal factors that
play a role in the establishment of the fungus in vivo, and (iv) problems
associated with antifungal therapy.
PMID- 10194470
TI - Pregnant rat uterus expresses high levels of the type 3 iodothyronine deiodinase.
AB - Although thyroid hormones are critically important for the coordination of
morphogenic processes in the fetus and neonate, premature exposure of the embryo
to levels of the hormones present in the adult is detrimental and can result in
growth retardation, malformations, and even death. We report here that the
pregnant rat uterus expresses extremely high levels of the type 3 iodothyronine
deiodinase (D3), which inactivates thyroxine and 3,3', 5-triiodothyronine by 5
deiodination. Both D3 mRNA and activity were present at the implantation site as
early as gestational day 9 (E9), when expression was localized using in situ
hybridization to uterine mesometrial and antimesometrial decidual tissue. At
later stages of gestation, uterine D3 activity remained very high, and the levels
exceeded those observed in the placenta and in fetal tissues. After days E12 and
E13, as decidual tissues regressed, D3 expression became localized to the
epithelial cells lining the recanalized uterine lumen that surrounds the fetal
cavity. These findings strongly suggest that the pregnant uterus, in addition to
the placenta, plays a critical role in determining the level of exposure of the
fetus to maternal thyroid hormones.
PMID- 10194471
TI - Deficiency of platelet-activating factor acetylhydrolase is a severity factor for
asthma.
AB - Asthma, a family of airway disorders characterized by airway inflammation, has an
increasing incidence worldwide. Platelet-activating factor (PAF) may play a role
in the pathophysiology of asthma. Its proinflammatory actions are antagonized by
PAF acetylhydrolase. A missense mutation (V279F) in the PAF acetylhydrolase gene
results in the complete loss of activity, which occurs in 4% of the Japanese
population. We asked if PAF acetylhydrolase deficiency correlates with the
incidence and severity of asthma in Japan. We found that the prevalence of PAF
acetylhydrolase deficiency is higher in Japanese asthmatics than healthy subjects
and that the severity of this syndrome is highest in homozygous-deficient
subjects. We conclude that the PAF acetylhydrolase gene is a modulating locus for
the severity of asthma.
PMID- 10194472
TI - Heteropolymerization of S, I, and Z alpha1-antitrypsin and liver cirrhosis.
AB - The association between Z alpha1-antitrypsin deficiency and juvenile cirrhosis is
well-recognized, and there is now convincing evidence that the hepatic inclusions
are the result of entangled polymers of mutant Z alpha1-antitrypsin. Four percent
of the northern European Caucasian population are heterozygotes for the Z
variant, but even more common is S alpha1-antitrypsin, which is found in up to
28% of southern Europeans. The S variant is known to have an increased
susceptibility to polymerization, although this is marginal compared with the
more conformationally unstable Z variant. There has been speculation that the two
may interact to produce cirrhosis, but this has never been demonstrated
experimentally. This hypothesis was raised again by the observation reported here
of a mixed heterozygote for Z alpha1-antitrypsin and another conformationally
unstable variant (I alpha1-antitrypsin; 39Arg-->Cys) identified in a 34-year-old
man with cirrhosis related to alpha1-antitrypsin deficiency. The conformational
stability of the I variant has been characterized, and we have used fluorescence
resonance energy transfer to demonstrate the formation of heteropolymers between
S and Z alpha1-antitrypsin. Taken together, these results indicate that not only
may mixed variants form heteropolymers, but that this can causally lead to the
development of cirrhosis.
PMID- 10194473
TI - Aldose reductase functions as a detoxification system for lipid peroxidation
products in vasculitis.
AB - Giant cell arteritis (GCA) is a systemic vasculitis preferentially affecting
large and medium-sized arteries. Inflammatory infiltrates in the arterial wall
induce luminal occlusion with subsequent ischemia and degradation of the elastic
membranes, allowing aneurysm formation. To identify pathways relevant to the
disease process, differential display-PCR was used. The enzyme aldose reductase
(AR), which is implicated in the regulation of tissue osmolarity, was found to be
upregulated in the arteritic lesions. Upregulated AR expression was limited to
areas of tissue destruction in inflamed arteries, where it was detected in T
cells, macrophages, and smooth muscle cells. The production of AR was highly
correlated with the presence of 4-hydroxynonenal (HNE), a toxic aldehyde and
downstream product of lipid peroxidation. In vitro exposure of mononuclear cells
to HNE was sufficient to induce AR production. The in vivo relationship of AR and
HNE was explored by treating human GCA temporal artery-severe combined
immunodeficiency (SCID) mouse chimeras with the AR inhibitors Sorbinil and
Zopolrestat. Inhibition of AR increased HNE adducts twofold and the number of
apoptotic cells in the arterial wall threefold. These data demonstrate that AR
has a tissue-protective function by preventing damage from lipid peroxidation. We
propose that AR is an oxidative defense mechanism able to neutralize the toxic
effects of lipid peroxidation and has a role in limiting the arterial wall injury
mediated by reactive oxygen species.
PMID- 10194474
TI - Surfactant protein-A enhances respiratory syncytial virus clearance in vivo.
AB - To determine the role of surfactant protein-A(SP-A) in antiviral host defense,
mice lacking SP-A (SP-A-/-) were produced by targeted gene inactivation. SP-A-/-
and control mice (SP-A+/+) were infected with respiratory syncytial virus (RSV)
by intratracheal instillation. Pulmonary infiltration after infection was more
severe in SP-A-/- than in SP-A+/+ mice and was associated with increased RSV
plaque-forming units in lung homogenates. Pulmonary infiltration with
polymorphonuclear leukocytes was greater in the SP-A-/- mice. Levels of
proinflammatory cytokines tumor necrosis factor-alpha and interleukin-6 were
enhanced in lungs of SP-A-/- mice. After RSV infection, superoxide and hydrogen
peroxide generation was deficient in macrophages from SP-A-/- mice, demonstrating
a critical role of SP-A in oxidant production associated with RSV infection.
Coadministration of RSV with exogenous SP-A reduced viral titers and inflammatory
cells in the lung of SP-A-/- mice. These findings demonstrate that SP-A plays an
important host defense role against RSV in vivo.
PMID- 10194475
TI - Macrophages are a significant source of type 1 cytokines during mycobacterial
infection.
AB - T-helper 1 (Th1) cells are believed to be the major producer of the type 1
cytokine interferon-gamma (IFN-gamma) in cell-mediated immunity against
intracellular infection. We have investigated the ability of macrophages to
release type 1 cytokines and their regulatory mechanisms using both in vivo and
in vitro models of pulmonary mycobacterial infection. During pulmonary infection
by live Mycobacterium bovis bacilli Calmette-Guerin (BCG) in wild-type mice, lung
macrophages released interleukin-12 (IL-12), IFN-gamma, and tumor necrosis factor
alpha (TNF-alpha), and expressed surface activation markers. However, macrophages
in infected IL-12(-/-) mice released TNF-alpha but not IFN-gamma and lacked
surface activation makers. In freshly isolated lung macrophages from naive IL-2(
/-) mice, mycobacteria alone released TNF-alpha but not IFN-gamma, whereas
exogenously added IL-12 alone released a minimum of IFN-gamma. However, these
macrophages released large quantities of IFN-gamma upon stimulation with both
mycobacteria and IL-12. In contrast, mycobacteria and exogenous IFN-gamma
released only a minimum of endogenous IFN-gamma. Endogenous IL-18 (IFN-gamma
inducing factor) played little role in IFN-gamma responses by macrophages
stimulated by mycobacteria and IL-12. Our data reveal that macrophages are a
significant source of type 1 cytokines during mycobacterial infection and that
both IL-12 and intracellular pathogens are required for the release of IFN-gamma
but not TNF-alpha. These findings suggest that macrophages regulate cell-mediated
immunity by releasing not only IL-12 and TNF-alpha but also IFN-gamma and that
full activation of IFN-gamma response in macrophages is tightly regulated.
PMID- 10194476
TI - Plasma from human mothers of fetuses with severe arthrogryposis multiplex
congenita causes deformities in mice.
AB - Arthrogryposis multiplex congenita (AMC) is characterized by fixed joint
contractures and other deformities, sometimes resulting in fetal death. The cause
is unknown in most cases, but some women with fetuses affected by severe AMC have
serum antibodies that inhibit fetal acetylcholine receptor (AChR) function, and
antibodies to fetal antigens might play a pathogenic role in other congenital
disorders. To investigate this possibility, we have established a model by
injecting pregnant mice with plasma from four anti-AChR antibody-positive women
whose fetuses had severe AMC. We found that human antibodies can be transferred
efficiently to the mouse fetus during the last few days of fetal life. Many of
the fetuses of dams injected with AMC maternal plasmas or Ig were stillborn and
showed fixed joints and other deformities. Moreover, similar changes were found
in mice after injection of a serum from one anti-AChR antibody-negative mother
who had had four AMC fetuses. Thus, we have confirmed the role of maternal
antibodies in cases of AMC associated with maternal anti-AChR, and we have
demonstrated the existence of pathogenic maternal factors in one other case.
Importantly, this approach can be used to look at the effects of other maternal
human antibodies on development of the fetus.
PMID- 10194477
TI - Proteolysis of monocyte CD14 by human leukocyte elastase inhibits
lipopolysaccharide-mediated cell activation.
AB - Human leukocyte elastase (HLE), a polymorphonuclear neutrophil (PMN) serine
proteinase, is proteolytically active on some membrane receptors at the surface
of immune cells. The present study focused on the effect of HLE on the expression
of CD14, the main bacterial lipopolysaccharide (LPS) receptor at the surface of
monocytes. HLE exhibited a time- and concentration-dependent downregulatory
effect on CD14 surface expression. A 30-minute incubation of 3 microM HLE was
required to display 95% disappearance of the receptor. This downregulation
resulted from a direct proteolytic process, not from a shedding consecutive to
monocyte activation as observed upon challenge with phorbol myristate acetate
(PMA). To confirm that CD14 is a substrate for HLE, this enzyme was incubated
with recombinant human CD14 (Mr approximately 57,000), and proteolysis was
further analyzed by immunoblot analysis. Cleavage of the CD14 molecule was
directly evidenced by the generation of short-lived fragments (Mr approximately
47,000 and 30,000). As a consequence of the CD14 proteolysis, a decrease in the
responsiveness of monocytes to LPS was observed, as assessed by measuring tumor
necrosis factor-alpha (TNF-alpha) formation. This inhibition was only observed
with 1 ng/ml of LPS, i.e., when only the CD14-dependent pathway was involved. At
a higher LPS concentration, such as 10 microgram/ml, when CD14-independent
pathways were operative, this inhibition was overcome. The direct proteolysis by
HLE of the membrane CD14 expressed on monocytes illustrates a potential anti
inflammatory effect of HLE through inhibition of LPS-mediated cell activation.
PMID- 10194478
TI - Exogenous administration of heme oxygenase-1 by gene transfer provides protection
against hyperoxia-induced lung injury.
AB - Heme oxygenase-1 (HO-1) confers protection against a variety of oxidant-induced
cell and tissue injury. In this study, we examined whether exogenous
administration of HO-1 by gene transfer could also confer protection. We first
demonstrated the feasibility of overexpressing HO-1 in the lung by gene transfer.
A fragment of the rat HO-1 cDNA clone containing the entire coding region was
cloned into plasmid pAC-CMVpLpA, and recombinant adenoviruses containing the rat
HO-1 cDNA fragment Ad5-HO-1 were generated by homologous recombination.
Intratracheal administration of Ad5-HO-1 resulted in a time-dependent increase in
expression of HO-1 mRNA and protein in the rat lungs. Increased HO-1 protein
expression was detected diffusely in the bronchiolar epithelium of rats receiving
Ad5-HO-1, as assessed by immunohistochemical studies. We then examined whether
ectopic expression of HO-1 could confer protection against hyperoxia-induced lung
injury. Rats receiving Ad5-HO-1, but not AdV-betaGal, a recombinant adenovirus
expressing Escherichia coli beta-galactosidase, before exposure to hyperoxia
(>99% O2) exhibited marked reduction in lung injury, as assessed by volume of
pleural effusion and histological analyses (significant reduction of edema,
hemorrhage, and inflammation). In addition, rats receiving Ad5-HO-1 also
exhibited increased survivability against hyperoxic stress when compared with
rats receiving AdV-betaGal. Expression of the antioxidant enzymes manganese
superoxide dismutase (Mn-SOD) and copper-zinc superoxide dismutase (CuZn-SOD) and
of L-ferritin and H-ferritin was not affected by Ad5-HO-1 administration.
Furthermore, rats treated with Ad5-HO-1 exhibited attenuation of hyperoxia
induced neutrophil inflammation and apoptosis. Taken together, these data suggest
the feasibility of high-level HO-1 expression in the rat lung by gene delivery.
To our knowledge, we have demonstrated for the first time that HO-1 can provide
protection against hyperoxia-induced lung injury in vivo by modulation of
neutrophil inflammation and lung apoptosis.
PMID- 10194479
TI - Extracellular superoxide dismutase in the airways of transgenic mice reduces
inflammation and attenuates lung toxicity following hyperoxia.
AB - Extracellular superoxide dismutase (EC-SOD, or SOD3) is the major extracellular
antioxidant enzyme in the lung. To study the biologic role of EC-SOD in hyperoxic
induced pulmonary disease, we created transgenic (Tg) mice that specifically
target overexpression of human EC-SOD (hEC-SOD) to alveolar type II and
nonciliated bronchial epithelial cells. Mice heterozygous for the hEC-SOD
transgene showed threefold higher EC-SOD levels in the lung compared with wild
type (Wt) littermate controls. A significant amount of hEC-SOD was present in the
epithelial lining fluid layer. Both Tg and Wt mice were exposed to normobaric
hyperoxia (>99% oxygen) for 48, 72, and 84 hours. Mice overexpressing hEC-SOD in
the airways attenuated the hyperoxic lung injury response, showed decreased
morphologic evidence of lung damage, had reduced numbers of recruited
inflammatory cells, and had a reduced lung wet/dry ratio. To evaluate whether
reduced numbers of neutrophil infiltration were directly responsible for the
tolerance to oxygen toxicity observed in the Tg mice, we made Wt and Tg mice
neutropenic using anti-neutrophil antibodies and subsequently exposed them to 72
hours of hyperoxia. Both Wt and Tg neutrophil-depleted (ND) mice have less severe
lung injury compared with non-ND animals, thus providing direct evidence that
neutrophils recruited to the lung during hyperoxia play a distinct role in the
resultant acute lung injury. We conclude that oxidative and inflammatory
processes in the extracellular lung compartment contribute to hyperoxic-induced
lung damage and that overexpression of hEC-SOD mediates a protective response to
hyperoxia, at least in part, by attenuating the neutrophil inflammatory response.
PMID- 10194480
TI - Disruption of LDL receptor gene in transgenic SREBP-1a mice unmasks
hyperlipidemia resulting from production of lipid-rich VLDL.
AB - Transgenic mice that overexpress the nuclear form of sterol regulatory element
binding protein-1a (SREBP-1a) in liver (TgBP-1a mice) were shown previously to
overproduce cholesterol and fatty acids and to accumulate massive amounts of
cholesterol and triglycerides in hepatocytes. Despite the hepatic overproduction
of lipids, the plasma levels of cholesterol ( approximately 45 mg/dl) and
triglycerides ( approximately 55 mg/dl) were not elevated, perhaps owing to
degradation of lipid-enriched particles by low-density lipoprotein (LDL)
receptors. To test this hypothesis, in the current studies we bred TgBP-1a mice
with LDL receptor knockout mice. As reported previously, LDLR-/- mice manifested
a moderate elevation in plasma cholesterol ( approximately 215 mg/dl) and
triglycerides ( approximately 155 mg/dl). In contrast, the doubly mutant TgBP
1a;LDLR-/- mice exhibited marked increases in plasma cholesterol ( approximately
1,050 mg/dl) and triglycerides ( approximately 900 mg/dl). These lipids were
contained predominantly within large very-low-density lipoprotein (VLDL)
particles that were relatively enriched in cholesterol and apolipoprotein E.
Freshly isolated hepatocytes from TgBP-1a and TgBP-1a;LDLR-/- mice overproduced
cholesterol and fatty acids and secreted increased amounts of these lipids into
the medium. Electron micrographs of livers from TgBP-1a mice showed large amounts
of enlarged lipoproteins within the secretory pathway. We conclude that the TgBP
1a mice produce large lipid-rich lipoproteins, but these particles do not
accumulate in plasma because they are degraded through the action of LDL
receptors.
PMID- 10194481
TI - Regulation of TH1- and TH2-type cytokine expression and action in atopic
asthmatic sensitized airway smooth muscle.
AB - CD4(+) T helper (TH)1- and TH2-type cytokines reportedly play an important role
in the pathobiology of asthma. Recent evidence suggests that proasthmatic changes
in airway smooth muscle (ASM) responsiveness may be induced by the autocrine
release of certain proinflammatory cytokines by the ASM itself. We examined
whether TH1- and TH2-type cytokines are expressed by atopic asthmatic sensitized
ASM and serve to autologously regulate the proasthmatic phenotype in the
sensitized ASM. Expression of these cytokines and their receptors was examined in
isolated rabbit and human ASM tissues and cultured cells passively sensitized
with sera from atopic asthmatic patients or control subjects. Relative to
controls, atopic sensitized ASM cells exhibited an early increased mRNA
expression of the TH2-type cytokines, interleukin-5 (IL-5) and granulocyte
macrophage colony-stimulating factor (GM-CSF), and their receptors. This was
later followed by enhanced mRNA expression of the TH1-type cytokines, IL-2, IL
12, and interferon-gamma (IFN-gamma), as well as their respective receptors. In
experiments on isolated ASM tissue segments (a) exogenous administration of IL-2
and IFN-gamma to atopic asthmatic serum-sensitized ASM ablated both their
enhanced constrictor responsiveness to acetylcholine (ACh) and their attenuated
relaxation responsiveness to beta-adrenoceptor stimulation with isoproterenol,
and (b) administration of IL-5 and GM-CSF to naive ASM induced significant
increases in their contractility to ACh and impaired their relaxant
responsiveness to isoproterenol. Collectively, these observations provide new
evidence demonstrating that human ASM endogenously expresses both TH1- and TH2
type cytokines and their receptors, that these molecules are sequentially
upregulated in the atopic asthmatic sensitized state, and that they act to
downregulate and upregulate proasthmatic perturbations in ASM responsiveness,
respectively.
PMID- 10194482
TI - Differential regulation of inotropy and lusitropy in overexpressed Gsalpha
myocytes through cAMP and Ca2+ channel pathways.
AB - We investigated the mechanisms responsible for altered contractile and relaxation
function in overexpressed Gsalpha myocytes. Although baseline contractile
function (percent contraction) in Gsalpha mice was similar to that of wild-type
(WT) mice, left ventricular myocyte contraction, fura-2 Ca2+transients, and Ca2+
channel currents (ICa) were greater in Gsalpha mice in response to 10(-8) M
isoproterenol (ISO) compared with WT mice. The late phase of relaxation of the
isolated myocytes and fura-2 Ca2+ transients was accelerated at baseline in
Gsalpha but did not increase further with ISO. In vivo measurements using
echocardiography also demonstrated enhanced relaxation at baseline in Gsalpha
mice. Forskolin and CaCl2 increased contraction similarly in WT and Gsalpha mice.
Rp-cAMP, an inhibitor of protein kinase, blocked the increases in contractile
response and Ca2+ currents to ISO in WT and to forskolin in both WT and Gsalpha.
It also blocked the accelerated relaxation in Gsalpha at baseline but not the
contractile response to ISO in Gsalpha myocytes. Baseline measurements of cAMP
and phospholambation phosphorylation were enhanced in Gsalpha compared with WT.
These data indicate that overexpression of Gsalpha accelerates relaxation at end
diastolic but does not affect baseline systolic function in isolated myocytes.
However, the enhanced responses to sympathetic stimulation partly reflect
increased Ca2+ channel activity; i.e the cellular mechanisms mediating these
effects appear to involve a cAMP-independent as well as a cAMP-dependent pathway.
PMID- 10194483
TI - Subclavian artery resection and reconstruction for thoracic inlet cancers.
AB - PURPOSE: We previously described an original transcervical approach to resect
primary or secondary malignant diseases that invade the thoracic inlet (TI). The
purpose of this study was to evaluate the technical aspects and long-term results
of the resection and revascularization of the subclavian artery (SA). METHODS:
Between 1986 and 1998, 34 patients (mean age, 49 years) underwent en bloc
resection of TI cancer that had invaded the SA. The surgical approach was an L
shaped transclavicular cervicotomy in 33 patients. In 14 of these patients, this
approach was associated with a posterolateral thoracotomy (n = 10) or a posterior
midline approach (n = 4). In one patient, the procedure was achieved with a
single posterolateral thoracotomy approach. An end-to-end anastomosis was
performed in 16 patients. In one patient, a subclavian-left common carotid artery
transposition was performed. In one other patient, an end-to-end anastomosis was
performed between the proximal innominate artery and the SA. The right carotid
artery was transposed into the SA in an end-to-side fashion. In 16 patients,
prosthetic revascularization with a polytetrafluoroethylene graft was performed.
Thirty-three patients underwent postoperative radiation therapy. RESULTS: There
were no cases of perioperative death, neurologic sequelae, graft infections or
occlusions, or limb ischemia. There were two delayed asymptomatic
polytetrafluoroethylene graft occlusions at 12 and 31 months. The 5-year patency
rate was 85%. During this study, 20 patients died: 18 died of tumor recurrence (5
local and systemic and 13 systemic), one of respiratory failure, and one of an
unknown cause at 74 months. The overall 5-year survival rate was 36%, and the 5
year disease-free survival rate was 18%. CONCLUSION: Tumor arterial invasion per
se should not be a contraindication to TI cancer resection. This study shows that
cancers that invade the SA can be resected through an L-shaped transclavicular
cervicotomy, with good results with a concomitant revascularization of the SA.
PMID- 10194484
TI - Stripping the long saphenous vein reduces the rate of reoperation for recurrent
varicose veins: five-year results of a randomized trial.
AB - OBJECTIVE: The purpose of this study was to investigate the possible long-term
clinical advantages of stripping the long saphenous vein during routine primary
varicose vein surgery. METHODS: The study was designed as a 5-year, clinical and
duplex scan follow-up examination of a group of patients who were randomized to
stripping of the long saphenous vein during varicose vein surgery versus
saphenofemoral ligation alone. The study was conducted in the vascular unit of a
district general hospital. One hundred patients (133 legs) with uncomplicated
primary long saphenous varicose veins originally were randomized. After
invitation 5 years later, 78 patients (110 legs) underwent clinical review and
duplex scan imaging. RESULTS: Sixty-five patients remained pleased with the
results of their surgery (35 of 39 stripped vs 30 of 39 ligated; P = .13).
Reoperation, either done or awaited, for recurrent long saphenous veins was
necessary for three of 52 of the legs that underwent stripping versus 12 of 58
ligated legs. The relative risk was 0.28, with a 95% confidence interval of 0.13
to 0.59 (P = .02). Neovascularization at the saphenofemoral junction was
responsible for 10 of 12 recurrent veins that underwent reoperation and also was
the cause of recurrent saphenofemoral incompetence in 12 of 52 stripped veins
versus 30 of 58 ligated legs. The relative risk was 0.45, with a 95% confidence
interval of 0.26 to 0.78 (P = .002). CONCLUSION: Stripping reduced the risk of
reoperation by two thirds after 5 years and should be routine for primary long
saphenous varicose veins.
PMID- 10194485
TI - High-pressure, rapid-inflation pneumatic compression improves venous hemodynamics
in healthy volunteers and patients who are post-thrombotic.
AB - PURPOSE: Deep vein thrombosis (DVT) is a preventable cause of morbidity and
mortality in patients who are hospitalized. An important part of the mechanism of
DVT prophylaxis with intermittent pneumatic compression (IPC) is reduced venous
stasis with increased velocity of venous return. The conventional methods of IPC
use low pressure and slow inflation of the air bladder on the leg to augment
venous return. Recently, compression devices have been designed that produce high
pressure and rapid inflation of air cuffs on the plantar plexus of the foot and
the calf. The purpose of this study is to evaluate the venous velocity response
to high-pressure, rapid-inflation compression devices versus standard, low
pressure, slow-inflation compression devices in healthy volunteers and patients
with severe post-thrombotic venous disease. METHOD: Twenty-two lower extremities
from healthy volunteers and 11 lower extremities from patients with class 4 to
class 6 post-thrombotic chronic venous insufficiency were studied. With duplex
ultrasound scanning (ATL-Ultramark 9, Advanced Tech Laboratory, Bothell, Wash),
acute DVT was excluded before subject evaluation. Venous velocities were
monitored after the application of each of five IPC devices, with all the
patients in the supine position. Three high-pressure, rapid-compression devices
and two standard, low-pressure, slow-inflation compression devices were applied
in a random sequence. Maximal venous velocities were obtained at the common
femoral vein and the popliteal vein for all the devices and were recorded as the
mean peak velocity of three compression cycles and compared with baseline
velocities. RESULTS: The baseline venous velocities were higher in the femoral
veins than in the popliteal veins in both the volunteers and the post-thrombotic
subjects. Standard and high-pressure, rapid-inflation compression significantly
increased the popliteal and femoral vein velocities in healthy and post
thrombotic subjects. High-pressure, rapid-inflation compression produced
significantly higher maximal venous velocities in the popliteal and femoral veins
in both healthy volunteers and patients who were post-thrombotic as compared with
standard compression. Compared with the healthy volunteers, the patients who were
post-thrombotic had a significantly attenuated velocity response at both the
popliteal and the femoral vein levels. CONCLUSION: High-pressure, rapid-inflation
pneumatic compression increases popliteal and femoral vein velocity as compared
with standard, low-pressure, slow-inflation pneumatic compression. Patients with
post-thrombotic venous disease have a compromised hemodynamic response to all IPC
devices. However, an increased velocity response to the high-pressure, rapid
inflation compression device is preserved. High-pressure, rapid-inflation
pneumatic compression may offer additional protection from thrombotic
complications on the basis of an improved hemodynamic response, both in healthy
volunteers and in patients who were post-thrombotic.
PMID- 10194486
TI - Arterial aneurysms in patients infected with human immunodeficiency virus: a
distinct clinicopathology entity?
AB - Arterial aneurysms have only recently been associated with the human
immunodeficiency virus (HIV). The clinical and pathological features of 10 HIV
positive patients with arterial aneurysms were retrospectively evaluated. These
aneurysms were unusual in that they affected young black patients, occurred in
atypical sites, and tended toward multiplicity. Surgery was performed in eight
patients. Acute and chronic inflammatory changes were revealed by means of
histologic examination of the aneurysm walls, with occlusion of the vasa vasora
by inflammatory infiltrate or edema being a prominent feature. Culture of the
aneurysm wall or thrombus yielded positive results in two patients. The
association between HIV and aneurysms may be coincidental, caused by direct viral
action or by bacterial infection resulting from immunosuppression. Implications
for therapy are discussed, and the need for further study is highlighted.
PMID- 10194487
TI - Hemodialysis access: influence of the human immunodeficiency virus on patency and
infection rates.
AB - PURPOSE: The complication rate for patients who are dialysis dependent and
infected with the human immunodeficiency virus (HIV) and the role of viral
indicators (CD4 counts) as predictors of these complications are poorly
characterized. To determine the influence of HIV status and viral activity on
graft patency and infection rates, we retrospectively reviewed our results.
METHODS: Between June 1993 and March 1997, the charts of 104 patients (HIV+, n =
42; HIV-, n = 62) who required 112 hemodialysis access grafts were reviewed. Of
the 112 procedures, 55 (48%) were autologous arteriovenous fistulae (AVF)
procedures (HIV+, n = 23; HIV-, n = 32) and 57 (52%) were prosthetic expanded
polytetrafluoroethylene grafting procedures (HIV+, n = 27; HIV-, n = 30).
Transcutaneous catheter procedures were excluded from the study. The autologous
AVF procedures consisted of direct and transposed AVFs. Patency rates were
determined by means of life-table analysis. Infection rates and CD4 counts were
compared with the chi2 test and the Fisher exact test. Significance was accepted
at a P value of.05 or less. RESULTS: The cumulative 12-month and 24-month patency
rates for prosthetic grafts in patients who were HIV+ were 49% and 21%,
respectively, versus 77% and 45% for patients who were HIV-. The differences in
the prosthetic graft patency rates between these two groups were significant (P
=.05). The cumulative 12-month and 24-month patency rates for autologous AVF
procedures did not differ significantly. The AVF procedure patency rates were 72%
and 51%, respectively, in patients who were HIV+ versus 54% and 50% for patients
who were HIV-. The prosthetic graft infection rate for patients who were HIV+ and
HIV- were 30% and 7%, respectively ( P =.04). However, the infection rates in
autologous AVF procedures did not differ between the groups (9% vs 0%; P>.05).
The mean CD4+ cell counts were 174: CD4+ counts that were less than 200 did not
correlate with or predict the development of infection (P >.05). CONCLUSION: Our
data showed that prosthetic graft infection rates were increased and patency
rates were decreased in patients who were HIV+ as compared with patients who were
HIV- and HIV+ with autologous AVFs. There were no differences in patency rates or
infection rates in patients who had undergone autologous access procedures. Long
term graft patency rates were not affected by HIV status, and CD4+ lymphocyte
counts were not predictive of infection development. Because the prosthetic graft
infection rates exceeded those rates of autologous access procedures, we
recommend the vigorous use of autologous AVFs in all patients who are HIV+,
regardless of CD4+ count.
PMID- 10194488
TI - Renal artery stenosis treated with stent deployment: indications, technique, and
outcome for 108 patients.
AB - From January 1993 to May 1996, 108 patients (64 men, 44 women; mean age, 72
years; age range, 37 to 87 years) underwent 125 percutaneous transluminal
angioplasties and stent implantations primarily for atherosclerotic lesions of
the renal artery. Sixty-four patients underwent treatment for renovascular
hypertension (two antihypertensive medications or more), 32 patients underwent
treatment for a combination of hypertension and renal failure (serum creatinine
level >/=1.6 mg/dL), and a small group of six patients (5%) without hypertension
or diminished renal function underwent treatment to prevent the progression to
renal artery occlusion and kidney loss. Thirty-three patients (31%) had
renovascular hypertension that was classified as severe on three or more
medications, 31 patients (29%) had renovascular hypertension that was classified
as moderate on two medications, and 38 patients (35%) had renovascular
hypertension that was classified in the mild group on a single antihypertensive
agent. Stenotic lesions were located at the ostium of the renal artery in 82
cases (65%) and were ostial-adjacent (<5 mm from renal ostium) in the other 43
cases (34%). A total of 125 stents were deployed in 125 arteries (procedural
success 97.6%). Renovascular hypertension either was cured or was improved in 73
patients (68%), with 14 patients (13%) considered cured (normotensive on no
medications). The conditions of 29 patients (27%) were unchanged, and 6 patients
(5%) had worsening hypertension after surgery. We were unable to demonstrate a
statistically significant improvement in serum creatinine levels after renal
artery balloon angioplasty/stenting. Complications occurred in a total of nine
cases (7.2%), six of which were related to technical problems. One patient had
worsening renal insufficiency caused by contrast agent, and another patient had a
perinephric hematoma develop that necessitated evacuation. There were four
postoperative deaths (30-day mortality). Two of these deaths were caused by
postoperative myocardial infarction. The other two patients had progressive renal
failure develop that necessitated dialysis. These patients later died of the
disease process despite supportive care. Follow-up renal artery duplex scan
studies and angiograms were available on 96 patients (76%). The mean peak
systolic renal/aortic ratio on duplex scanning was 2.2. Life-table analysis
yielded a 74% primary patency rate and an 85% secondary patency rate at 36
months. This retrospective analysis showed the effectiveness of combining
percutaneous transluminal angioplasty with stent deployment for significant renal
artery stenosis to treat renovascular hypertension.
PMID- 10194489
TI - A prospective study to assess changes in proximal aortic neck dimensions after
endovascular repair of abdominal aortic aneurysms.
AB - OBJECTIVE: The purpose of this study was to detect any change in the proximal
neck diameter after endovascular repair of abdominal aortic aneurysm. METHODS:
The study was performed in a teaching hospital with an endovascular program on
112 patients who had undergone endovascular repair of abdominal aortic aneurysm.
The interventions were pre-endovascular and postendovascular repair of abdominal
aortic aneurysms with contrast-enhanced, spiral computerized tomography, and the
main outcome measures were change in aortic proximal neck diameter, change in
maximum aortic diameter, presence of endoleaks, and change in length from lowest
renal artery to aortic bifurcation. RESULTS: The median anterior-posterior and
transverse diameter decreased from 63.5 mm before surgery to 50.4 and 54.5 mm,
respectively, after surgery in a period of 4 years. This trend in reduction in
maximum diameter was not seen in the patients with endoleaks. There was no
significant change in the proximal neck diameters when measured at 5-mm intervals
after endovascular repair. There was also no significant change in the aortic
length after endovascular repair. CONCLUSION: We have not demonstrated any
evidence for proximal neck dilatation after endovascular repair of abdominal
aortic aneurysm.
PMID- 10194490
TI - Accurate assessment of abdominal aortic aneurysm with intravascular ultrasound
scanning: validation with computed tomographic angiography.
AB - PURPOSE: The purpose of this study was to assess the accuracy of intravascular
ultrasound (IVUS) parameters of abdominal aortic aneurysm, used for endovascular
grafting, in comparison with computed tomographic angiography (CTA). METHODS:
This study was designed as a descriptive study. Between March 1997 and March
1998, 16 patients with abdominal aortic aneurysms were studied with angiography,
IVUS (12.5 MHz), and CTA. The length of the aneurysm and the length and lumen
diameter of the proximal and distal neck obtained with IVUS were compared with
the data obtained with CTA. The measurements with IVUS were repeated by a second
observer to assess the reproducibility. Tomographic IVUS images were
reconstructed into a longitudinal format. RESULTS: IVUS results identified 31 of
32 renal arteries and four of five accessory renal arteries. A comparison of the
length measurements of the aneurysm and the proximal and distal neck obtained
with IVUS and CTA revealed a correlation of 0.99 (P <.001), with a coefficient of
variation of 9%. IVUS results tended to underestimate the length as compared with
the CTA results (0.48 +/- 0.52 cm; P <.001). A comparison of the lumen diameter
measurements of the proximal and distal neck derived from IVUS and CTA showed a
correlation of 0.93 (P <.001), with a coefficient of variation of 9%. IVUS
results tended to underestimate aneurysm neck diameter as compared with CTA
results (0.68 +/- 1.76 mm; P =.006). Interobserver agreement of IVUS length and
diameter measurements showed a good correlation (r = 1.0; P <.001), with
coefficients of variation of 3% and 2%, respectively, and no significant
differences (0.0 +/- 0.16 cm and 0.06 +/- 0.36 mm, respectively). The
longitudinal IVUS images displayed the important vascular structures and improved
the spatial insight in aneurysmal anatomy. CONCLUSION: Intravascular ultrasound
scanning results provided accurate and reproducible measurements of abdominal
aortic aneurysm. The longitudinal reconstruction of IVUS images provided
additional knowledge on the anatomy of the aneurysm and its proximal and distal
neck.
PMID- 10194491
TI - Laparoscopic aortofemoral bypass grafting: human cadaveric and initial clinical
experiences.
AB - PURPOSE: Postoperative complications are mainly related to the surgical trauma
derived from the extensive abdominal incision and dissection after a conventional
aortofemoral bypass grafting procedure. In an attempt to reduce postoperative
complications, a concept of video-endoscopic vascular surgery on the infrarenal
aortoiliac artery has been developed. On the basis of our experience with the
practicability of video-endoscopic vascular surgery in the pelvic region in an
animal study and in a pilot study of human cadavers, the purpose of this report
was to describe three different methods that we evaluated on human cadavers and
that we partly applied to patients. METHODS: In this experimental study, three
different approaches were used to perform video-endoscopic aortofemoral bypass
grafting. We performed an observational trial on human corpses (n = 24) with the
transabdominal-retroperitoneal approach (TARA), the extraperitoneal approach
(EPA), and the transabdominal left paracolic approach (TAPA). The EPA also was
applied to patients with aortoiliac occlusive diseases. RESULTS: The TARA on
cadavers (n = 4) soon was abandoned because it caused a burdensome sliding of the
intestine into the operative field adjacent to the renal vessels, particularly in
cases with obese subjects. In comparison, the TAPA (n = 6) with right-sided
positioning of the patient retained the intestine in the right upper abdomen
throughout the procedure. Until a surgeon actually is acquainted with the
anatomic landmarks and the laparoscopic preparation technique, the EPA (n = 14)
is a challenging procedure that necessitates thorough training. As with the TAPA,
the EPA represents a procedure that reveals constant exposure of the operating
field, even in cases with obese subjects. In the clinical observational study (n
= 7), aortobifemoral bypass grafting was achieved totally laparoscopically with
the EPA. The mean operating time was 6.5 hours and ranged from 3 to 10 hours.
Blood transfusions were necessary after surgery in three patients (range, 1 to 3
red packed blood cells). One patient, who had had occlusion of the inferior
mesenteric artery, died of ischemic colitis at postoperative day 10. The other
patients had uneventful postoperative courses with minor wound discomfort.
CONCLUSION: Laparoscopic vascular surgery seems to be a promising procedure to
minimize postoperative complications. On the basis of our experience, we do not
favor the TARA. Because it necessitates steep Trendelenburg positioning to
displace intra-abdominal organs, the TARA is not an appropriate approach,
particularly in obese and cardiopulmonary frail cases. Contrarily, the TAPA and
the EPA deliver potentially better results in terms of exposing the operative
field and thus reducing operating time and perioperative morbidity rates. A
prospective cadaveric and clinical trial may be justified to further evaluate the
use of these surgical techniques.
PMID- 10194492
TI - Familial carotid body tumors: a closer look.
AB - PURPOSE: A family spanning three generations with a history of familial carotid
body tumors (CBTs) was studied, and previously proposed hypotheses of tumor
characteristics and genetic mode of transmission were addressed. METHODS:
Clinically occult lesions in adult subjects were detected by means of high
resolution computed tomography. RESULTS: A 60% incidence of bilaterality of CBTs
associated with multiple paragangliomas was noted in the family studied. The
genetic mode for CBTs in this family was not simple autosomal dominant
transmission and appeared to be paternally directed with complete penetrance.
CONCLUSION: In patients with familial CBTs, high-resolution computed tomography
is recommended for early screening as a means of prompting diagnosis and
definitive treatment, an approach that minimizes morbidity and facilitates
surgical excision.
PMID- 10194493
TI - Carotid endarterectomy outcome with vein or Dacron graft patch angioplasty and
internal carotid artery shortening.
AB - OBJECTIVE: This analysis of the outcome of carotid endarterectomy (CEA) was
performed during a period of transition from the frequent use of autologous
greater saphenous vein grafting to the frequent use of Dacron graft patch
reconstruction and from the infrequent use to the moderate use of eversion
plication shortening of the endarterectomized internal carotid artery segment.
METHODS: From 1990 to 1997, 697 consecutive primary CEAs were performed on 326
men (61 bilateral CEAs) and 272 women (38 bilateral CEAs) with a mean age (+/-
SD) of 68 +/- 9 years. The indications were transient ischemic attack in 31% of
the patients, stroke or reversible ischemic neurologic deficit in 18%, global
ischemia in 12%, and asymptomatic stenosis >/=70% in 39%. Patch reconstruction
was performed in the 678 CEAs in which the arteriotomy extended distal to the
internal carotid artery bulb (97%; 370 saphenous vein grafts, 308 Dacron grafts).
Primary closure was used in the other 19 CEAs. Early in this series, saphenous
vein patching frequently was performed, with a gradual transition to the frequent
use of knitted Dacron grafts. Concurrent with this, the frequency of the
shortening of the internal carotid artery increased from 7% to 40%. Postoperative
duplex scans were obtained on 619 CEAs (91%). RESULTS: There were four deaths
(0.6%) in 30 days-three from myocardial infarction and one from hyperperfusion
stroke. Thirteen strokes (1.9%), nine ipsilateral and four contralateral,
occurred in 30 days. Four nonfatal strokes and one death occurred in the
saphenous vein group (3.2%), and eight strokes and two deaths occurred in the
Dacron graft group (1.4%; P =.16). The combined 30-day stroke or death rate was
2.3% (16/697), and the hospital rate was 1.7% (12/697). Of the three internal
carotid artery occlusions, two were identified at 2 months (one Dacron graft, one
saphenous vein) and one was identified at 1 year (Dacron graft). Nonocclusive
(>/=50%) restenosis was identified in 16 CEAs. Fifteen of these were in the
internal carotid artery. The cumulative Kaplan-Meier method of life-table
analysis for the >/=50% restenosis rate at 2 months, 6 months, 1 year, and 3
years for Dacron graft patched CEA was 1.7%, 2.3%, 8.8%, and 12.3% and for
saphenous vein patched CEA was 0.3%, 0.3%, 0.3%, and 1.1% ( P <.0001). At the
same time intervals, the >/=50% restenosis rate for internal carotid artery
shortening was 1.0%, 2.5%, 13.7%, and 19.5%, and, when shortening was not done,
the rate was 0.8%, 0.8%, 1.1%, and 3.1% (P <.0001). The >/=50% restenosis rate at
the same intervals for women was 0.8%, 1.3%, 5.2%, and 8.9%, and, for men, the
rate was 0.9%, 0.9%, 1.8%, and 2.5% (P =.11). Univariate analysis of the rate of
>/=50% restenosis in 3 years for the 346 vein patched (2; 0.6%) and 186 Dacron
graft patched (7; 3.8%) CEAs that did not have internal carotid artery shortening
gave a P value of .015. Similarly, Kaplan-Meier method analysis of this subset of
nonshortened CEAs gave a higher restenosis rate with Dacron graft patching (P
=.012). With multiple logistic regression, the >/=50% restenosis rate was
significantly associated with Dacron graft patching (P =.023; odds ratio, 4.5)
and internal carotid artery shortening (P =.025; odds ratio, 3.1) and was weakly
associated with female gender (P =.15; odds ratio, 2.0). Cox proportional hazards
model analysis for >/=50% restenosis gave relative risk ratios of 3.0 (1.6 to
6.8; 95% confidence interval [CI]) for Dacron graft versus vein patching, 2.0
(1.2 to 3.3; 95% CI) for shortening versus not shortening, and 1.5 (0.9 to 2.4;
95% CI) for female versus male gender. CONCLUSION: CEA patching with Dacron
grafts and saphenous vein grafts have similar low perioperative thrombosis,
stroke, and death rates, although the stroke and death rates were slightly higher
but not statistically different when Dacron grafts were used. Dacron graft
patched CEAs are more likely to develop >/=50% restenosis than are those that are
patched
PMID- 10194494
TI - Assessment of ocular perfusion after carotid endarterectomy with color-flow
duplex scanning.
AB - PURPOSE: The purpose of this study was to assess the effect of carotid
endarterectomy (CEA) on ocular perfusion with the measurement of the ophthalmic
artery (OA) and the central retinal artery (CRA) flow velocities with color-flow
ocular duplex scanning (ODS). Ocular hemodynamics also were examined in a subset
of patients with visual symptoms in an attempt to characterize the origin of the
ocular symptoms and their response to surgery. METHODS: Twenty-five patients with
internal carotid artery stenoses (>/=70%) underwent 29 CEAs. All the patients
underwent ODS for the measurement of the peak systolic velocity (PSV) in the OA
and the CRA of the ipsilateral eye before and after CEA. The preoperative and
postoperative flow velocities were compared in all the patients and in the
patients with and without visual symptoms. RESULTS: The preoperative PSV in the
OA was 21.6 +/- 2.2 cm/s and in the CRA was 7.7 +/- 0.7 cm/s. These values were
reduced as compared with normative values (OA, 37.8 cm/s; CRA, 10.7 cm/s). After
CEA, the PSV increased significantly in both vessels (postoperative OA, 38.6 +/-
2.5 cm/s, P <.0001; postoperative CRA, 12.1 +/- 0.9 cm/s, P =.0008). Fifteen of
the 29 CEAs were performed for visual symptoms. The patients with ocular symptoms
had significantly lower preoperative PSVs in the CRA as compared with those
patients without visual symptoms (CRA with ocular symptoms, 6.5 +/- 0.8 cm/s; CRA
with no ocular symptoms, 9.4 +/- 0.9 cm/s; P =.02). The PSV in the OA was not
significantly lower in the patients with ocular symptoms. Eight patients (28%)
were found to have reversed OA flow before surgery, but only three patients had
ocular symptoms. All eight patients had normal antegrade flow in the OA after
surgery. CONCLUSION: Severe carotid stenosis may be associated with reduced
ocular perfusion, which can be quantitatively evaluated with ODS. Reduced OA and
CRA flow velocities are corrected with successful CEA. The patients with ocular
symptoms were observed to have significant reductions in CRA flow velocities.
Reversed flow in the OA was not a marker for ocular symptoms in this study. ODS
can identify global ocular ischemia and may be helpful in the evaluation of
patients with atypical visual symptoms or with amaurosis fugax and no evidence of
retinal emboli.
PMID- 10194495
TI - Carotid endarterectomy in patients with significant renal dysfunction.
AB - PURPOSE: Recent reports suggest that carotid endarterectomy (CEA) should not be
performed in patients with end-stage renal disease (ESRD) because of an
unacceptable rate of perioperative stroke and other morbidity. Because these
conclusions were based on a small number of patients, we reviewed the
perioperative and long-term outcome of patients with ESRD and chronic renal
insufficiency (CRI) who underwent CEA at our institution. METHODS: The 1081
patients who had a CEA between 1990 and 1997 were cross-referenced with those
patients in whom renal insufficiency had been diagnosed. These charts were
reviewed for patient demographics and perioperative and long-term outcome.
Patients undergoing CEA during a 1-year period (1993) served as controls.
RESULTS: Fifty-one CEAs were performed in 44 patients with CRI (32 in 27
patients) and ESRD (19 in 17 patients). In the CRI+ESRD group, 66.7% were
symptomatic, and 70.7% of the control group were symptomatic. Six operations
(11.8%) in the CRI+ESRD group were redo endarterectomies. There were no
perioperative strokes in the CRI+ESRD group, but one patient died 29 days
postoperatively because of a myocardial infarction, for a combined stroke
mortality rate of 2.0%. The control group had a 2.6% combined stroke-mortality
rate. Long-term survival analysis revealed a 4-year survival rate of 12% for
patients with ESRD and 54% for patients with CRI, compared with 72% for controls
(P <.05). CONCLUSION: CEA can be performed safely in patients with ESRD or CRI,
with perioperative stroke and death rates equivalent to that of patients without
renal dysfunction. However, the benefit of long-term stroke prevention in the
asymptomatic patient with ESRD is in question because of the high 4-year
mortality rate of this patient population.
PMID- 10194496
TI - Endothelial-dependent vasodilation is associated with increases in the
phosphorylation of a small heat shock protein (HSP20).
AB - PURPOSE: Increases in the phosphorylation of a small heat shock protein (HSP20)
are associated with cyclic nucleotide-dependent vasorelaxation. The effect of
pressure and flow on vessel diameter was studied. We hypothesized that
physiologic conditions that induce vasorelaxation would lead to increases in
HSP20 phosphorylation. METHODS: Flow-dependent changes in vessel diameter, at
different intraluminal pressures, were measured with a laser optical micrometer
in intact bovine carotid arteries. Experiments were performed in the presence and
absence of norepinephrine (10(-5) mol/L). Increases in the phosphorylation of
HSP20 were determined with isoelectric focusing immunoblots. RESULTS: The
increase in vessel diameter was most significant at low intraluminal pressures
(20 mm Hg), high flow rates (200 mL/min), and in the presence of the
vasoconstrictor norepinephrine (10(-5) mol/L). The addition of methylene blue (a
guanylate cyclase inhibitor) completely inhibited flow-induced vasodilation.
Under conditions in which maximal flow induced vasodilation occurred, there were
significant increases in the phosphorylation of HSP20. CONCLUSION: Flow-dependent
vasodilation in isolated perfused segments of bovine carotid arteries was maximal
when the intraluminal pressures were low and when the vessels were precontracted
with norepinephrine. Flow-dependent vasodilation was inhibited by methylene blue
and was associated with increases in the phosphorylation of HSP20, suggesting
that the vasodilation was mediated by endothelial production of nitric oxide.
PMID- 10194497
TI - Effects of somatostatin, somatostatin analogs, and endothelial cell somatostatin
gene transfer on smooth muscle cell proliferation in vitro.
AB - OBJECTIVE: Somatostatin analogs inhibit neointimal hyperplasia and smooth muscle
cell (SMC) proliferation in vivo. The gene transfer of somatostatin to
endothelial cells (ECs) represents a potential means of local delivery of
somatostatin to areas of arterial injury. This study tested the hypothesis that
the retroviral gene transfer of somatostatin to ECs would inhibit SMC
proliferation in vitro and evaluated the effects of somatostatin analogs on DNA
synthesis and the growth of SMCs. METHODS: Media transfer and coculture were used
to determine the effects of somatostatin-producing ECs on SMC proliferation in
vitro. The effects of a variety of somatostatin isoforms and analogs on the
proliferation of SMCs, mitogenesis of serum-restimulated quiescent SMCs, and
arterial explants were measured. RESULTS: Despite the production of biologically
relevant concentrations of somatostatin by ECs, no inhibition of SMC
proliferation was noted. Somatostatin analogs inhibited DNA synthesis in arterial
explants but did not inhibit either DNA synthesis or growth of cultured SMCs,
which showed a likely effect of somatostatin on the initial transition in SMC
phenotype. CONCLUSION: Somatostatin exerts inhibitory effects on SMC
proliferation only during the early transition to a proliferative phenotype.
There are significant differences between this in vivo transition and the
standard serum-restimulated model of cultured SMCs. These differences may account
for the failure of somatostatin to inhibit SMC proliferation in the standard in
vitro models.
PMID- 10194498
TI - Immunosuppression with FK506 in rat arterial allografts: fate of allogeneic
endothelial cells.
AB - PURPOSE: This study clarified the efficacy of low-dose FK506 and the possibility
of discontinuing the use of FK506. METHODS: Fresh carotid arteries were
allografted from ACI rats to Lewis rats. FK506 (0.2 mg/kg/day) was given
intramuscularly from day 3 after transplantation until the rats were killed
(group III), or it was given for 4 weeks and then discontinued (group IV).
Isogeneic (group I) and allogeneic (group II) models served as untreated control
groups. Grafts were harvested on days 0, 1, 3, 7, 14, 21, 28, 70, and 105 after
transplantation. Histological evaluation and measurement of the endothelial cell
(EC)-covered area were performed by means of scanning electron microscopy.
RESULTS: In group I, ECs were denuded immediately after transplantation and
subsequently regenerated within 2 weeks. In group II, after denudation and
regeneration of ECs, massive leukocyte adhesion and subsequent destruction of
regenerated ECs, followed by intimal hyperplasia, were observed. In group III,
FK506 suppressed rejection almost completely, without intimal hyperplasia. In
group IV, severe rejection and denudation of regenerated intima appeared 2 weeks
after the use of FK506 ended. CONCLUSION: The denudation and regeneration of ECs
may play an important role in the process of rejection and graft performance.
FK506 proved to be successful in rat arterial allografting, and ECs of donor
origin could survive on the allograft as long as FK506 was effective; however,
cessation of the use of FK506 resulted in severe destruction of intima. To
prevent allograft failure, long-term administration of an immunosuppressant is
essential.
PMID- 10194499
TI - The role of radial elastic properties in the development of aortic dissections.
AB - PURPOSE: The response of the upper and lower thoracic aorta to radial tensile
stresses was compared with the response to circumferential and longitudinal
stresses to understand the role of tensile stress in the tearing phase of an
aortic dissection. METHODS: Square tissue samples (1.6 by 1.6 cm) were cut from
the upper and lower segments of six porcine thoracic aortas and were elongated in
the radial direction with a tensile testing machine. The radial extensibility of
the thoracic aorta was compared with adjacent tissue samples that were tested in
tension in the circumferential and longitudinal directions based on Young's
modulus (ie, the ratio of tensile stress to strain). RESULTS: The elastic
properties of the thoracic aorta in the radial direction were markedly different
from both the circumferential and longitudinal properties. The average Young's
modulus (calculated immediately before failing) was significantly lower in the
radial direction for both the upper and lower thoracic segments (61.4 +/- 4.3
kPa, SEM) than the Young's modulus of corresponding segments in the
circumferential and longitudinal directions that were not tested to failure
(151.1 +/- 8.6 kPa and 112.7 +/- 9.2 kPa, respectively; P <. 05). Sections 7
micrometer thick were collected from four samples obtained from one upper
thoracic aorta that were strained at 0, 1.0, 2.5, and 4.0 and then stained either
with Movat's pentachrome or with hematoxylin and eosin. Histological analysis of
the samples stressed in the radial direction revealed that smooth muscle cells
were torn loose from their attachments to each other and to adjacent elastin.
CONCLUSION: Although the aorta normally functions under radial compressive
stresses associated with lumen blood pressure, these results show that the aorta
tears radially at a much lower value of stress than would have been predicted
from previous studies that have reported longitudinal and circumferential Young's
modulus. This could explain why dissections propagate readily once the initial
tear occurs.
PMID- 10194500
TI - Celiomesenteric anomaly with concurrent aneurysm.
AB - We describe a rare case of a celiomesenteric anomaly with concurrent aneurysm.
The patient, a 53-year-old man, had no abdominal pain or discomfort. The presence
of a celiac artery aneurysm was suspected on the basis of the results of
abdominal computerized tomographic scanning and echo ultrasound scanning
performed because of proteinuria. Intra-arterial digital subtraction angiographic
results showed the anomaly and aneurysm. Because of the risk of rupture of the
aneurysm, the lesion was repaired surgically, with the placement of an
interpositional prosthetic graft. We found no previous reports of celiomesenteric
anomaly with concurrent aneurysm repaired with prosthetic graft.
PMID- 10194501
TI - Left subclavian artery aneurysm: two cases of rare congenital etiology.
AB - Subclavian artery aneurysms are uncommon. The most common causes of these
aneurysms are atherosclerosis and traumatic pseudoaneurysm. We report two cases
of rare congenial left subclavian artery aneurysms. Diagnosis with aortography
and treatment with resection with bypass grafting are the optimal approaches to
avoid life-threatening and limb-threatening ischemia.
PMID- 10194502
TI - Splenic vein aneurysm: is it a surgical indication?
AB - Splenic vein aneurysms are rare and are usually caused by portal hypertension.
Symptoms are unusual, but may include rupture or abdominal pain. Diagnosis can
usually be made either by means of duplex ultrasonography or computed tomography
scanning. Treatment varies from noninvasive follow-up to aneurysm excision. We
report an expanding splenic vein aneurysm in a young woman with abdominal and
back pain and no history of portal hypertension. She was treated with aneurysm
excision and splenectomy.
PMID- 10194503
TI - Late rupture of a saphenous vein aortorenal graft.
PMID- 10194504
TI - Unilateral iliac vein occlusion, caused by bladder enlargement, simulating deep
venous thrombosis.
AB - A variety of conditions cause unilateral leg swelling and thus mimic deep venous
thrombosis (DVT). A heretofore-underappreciated condition that may lead to
unilateral iliac vein compression, simulating DVT, is massive enlargement of the
bladder caused by urinary retention. A case that demonstrates this condition is
described. Although this disorder has been reported only three times before, its
occurrence should be recognized by clinicians in light of the overall aging of
our society. In addition, this case highlights the need for careful and thorough
evaluation of patients who have unilateral lower-extremity edema.
PMID- 10194505
TI - Bypass graft of an occluded inferior vena cava: report of a case with patency at
five years.
AB - Venous reconstructive surgery for chronic occlusive disease has evolved slower
than its arterial counterpart. Factors intrinsic to the venous system that have
been implicated in discouraging experimental and clinical results include
enhanced graft thrombogenicity, low velocity of blood flow, and wall
collapsibility. 1,2 We present a case of a 24-year-old man with symptomatic
occlusion of the inferior vena cava, treated with a prosthetic bypass graft to
the supra diaphragmatic cava. The graft was patent 5 years later, and the patient
remained asymptomatic.
PMID- 10194506
TI - Video-assisted crossover iliofemoral obturator bypass grafting: a minimally
invasive approach to extra-anatomic lower limb revascularization.
AB - Graft infection continues to be one of the most feared complications in vascular
surgery. It can lead to disruption of anastomoses with life-threatening bleeding,
thrombosis of the bypass graft, and systemic septic manifestations. One method to
ensure adequate limb perfusion after removal of an infected aortofemoral graft is
extra-anatomical bypass grafting. We used a minimally invasive, video-assisted
approach to implant a crossover iliofemoral obturator bypass graft in a patient
with infection of the left limb of an aortofemoral bifurcated graft. This appears
to be the first case report describing the use of this technique.
PMID- 10194507
TI - Mastication steal: an unusual precipitant of cerebrovascular insufficiency.
AB - An 83-year-old man had episodic dizziness, visual disturbance, and facial and
extremity weakness associated with eating. Occlusion of the ipsilateral common
carotid artery and stenosis or occlusion of the major collateral sources were
demonstrated. We believe this anatomic configuration, combined with increases in
demand for external carotid artery blood flow necessitated by the act of chewing,
resulted in a vascular steal syndrome. An extended carotid endarterectomy was
performed, and there were no additional episodes.
PMID- 10194508
TI - Spontaneous popliteal artery dissection: a case report and review of the
literature.
AB - Spontaneous arterial dissection of a peripheral artery involving an extremity is
a rare event. We report a case of atraumatic, nonaneurysmal dissection of the
popliteal artery that occurred in a 62-year-old man who was admitted with
progressive right lower-extremity claudication. Preoperative arteriography was
suggestive of arterial dissection, and surgical treatment was undertaken before
irreversible ischemia developed. Intraoperatively, a dissection of the popliteal
artery was observed, and the patient underwent femoral-popliteal bypass grafting
with the ipsilateral, greater saphenous vein and the popliteal artery was ligated
distal to the dissection. Spontaneous dissection limited to the popliteal artery
has not previously been reported in the literature. Successful management depends
on consideration of the diagnosis, particularly when other, more common diseases
have been excluded.
PMID- 10194509
TI - Posterior approach to the deep femoral artery.
AB - Unusual surgical approaches to the deep femoral artery are valuable when the
standard anterior approach is difficult because of scarring or infection. A
posterior approach to the deep femoral artery in patients, in whom all other
approaches were unsuitable, is described.
PMID- 10194510
TI - Access to occluded infrainguinal bypass grafts with a loopsnare.
AB - Thrombolysis for the treatment of occluded bypass grafts is used in selected
clinical circumstances. Unfortunately, a minority of these procedures are
technical failures because of the inability to access the occluded graft. We
describe a technique that greatly increases the chances of technical success.
PMID- 10194511
TI - Heat shock proteins: a review of the molecular chaperones.
PMID- 10194512
TI - Chronic leg ulcers: the impact of venous disease.
PMID- 10194513
TI - Hormonal regulation of apolipoprotein AI.
AB - Apolipoprotein AI (apo AI) is the major protein component of the serum high
density lipoprotein (HDL) particles. The antiatherogenic properties of apo AI
alone or as part of HDL and their inverse correlation with the incidence of
coronary heart disease underlie the clinical importance of the protein. A
detailed understanding of the mechanisms by which apo AI is regulated will help
us develop new and better ways to manipulate expression of the protein. Although
there are many factors that influence apo AI expression, endogenous hormones are
attractive because simple changes in abundance of these compounds will alter gene
activity. Hormones belonging to the thyroid/steroid family that influence
activity of the gene include thyroid hormone, glucocorticoids, gender-specific
steroids and retinoic acid. Whereas thyroid, glucocorticoid and estradiol enhance
activity of the gene, retinoic acid and androgens decrease it. The mechanisms
that mediate the effects of the hormones include direct effects of the ligand and
nuclear receptor complex on gene activity. However, indirect means involving the
participation of transcription factors other than the hormone receptors are also
possible. In summary, members of the same hormone family may have different
mechanisms that mediate their activities on apo AI gene activity.
PMID- 10194514
TI - The structure and function of the ATP-sensitive K+ channel in insulin-secreting
pancreatic beta-cells.
AB - ATP-sensitive K+ channels (KATP channels) play important roles in many cellular
functions by coupling cell metabolism to electrical activity. The KATP channels
in pancreatic beta-cells are thought to be critical in the regulation of glucose
induced and sulfonylurea-induced insulin secretion. Until recently, however, the
molecular structure of the KATP channel was not known. Cloning members of the
novel inwardly rectifying K+ channel subfamily Kir6.0 (Kir6.1 and Kir6.2) and the
sulfonylurea receptors (SUR1 and SUR2) has clarified the molecular structure of
KATP channels. The pancreatic beta-cell KATP channel comprises two subunits: a
Kir6.2 subunit and an SUR1 subunit. Molecular biological and molecular genetic
studies have provided insights into the physiological and pathophysiological
roles of the pancreatic beta-cell KATP channel in insulin secretion.
PMID- 10194515
TI - Expression of cyclo-oxygenase types-1 and -2 in human fetal membranes throughout
pregnancy.
AB - Human labour is associated with increased prostaglandin synthesis within the
fetal membranes. We have studied the expression of the two isoforms of the
central prostaglandin synthetic enzyme, cyclo-oxygenase (COX-1 and COX-2), in
human fetal membranes throughout pregnancy, at mRNA, protein and activity levels.
COX-1 mRNA expression was low in human amnion and chorion-decidua and did not
change with gestational age. COX-2 mRNA expression in fetal membranes increased
with gestational age, with significant up-regulation prior to the onset of labour
and in association with labour. Protein concentrations of COX-1 did not change,
whilst concentrations of COX-2 increased from the first to the third trimester.
COX activity increased with gestational age and in association with labour,
although prostaglandin production in fetal membranes collected after labour was
reduced, suggesting reduced substrate supply. These data suggest that it is up
regulation of COX-2, rather than of COX-1, which mediates increased prostaglandin
synthesis within the fetal membranes at term. Much of the increase in COX-2
expression precedes the onset of labour, suggesting that it is a cause, rather
than a consequence, of labour.
PMID- 10194516
TI - Polyamine biosynthesis inhibitors alter protein-protein interactions involving
estrogen receptor in MCF-7 breast cancer cells.
AB - We investigated the effects of polyamine biosynthesis inhibition on the
estrogenic signaling pathway of MCF-7 breast cancer cells using a protein-protein
interaction system. Estrogen receptor (ER) linked to glutathione-S-transferase
(GST) was used to examine the effects of two polyamine biosynthesis inhibitors,
difluoromethylornithine (DFMO) and CGP 48664. ER was specifically associated with
a 45 kDa protein in control cells. In cells treated with estradiol, nine proteins
were associated with ER. Cells treated with polyamine biosynthesis inhibitors in
the absence of estradiol retained the binding of their ER with a 45 kDa protein
and the ER also showed low-affinity interactions with a number of cellular
proteins; however, these associations were decreased by the presence of estradiol
and the inhibitors. When samples from the estradiol+DFMO treatment group were
incubated with spermidine prior to GST-ER pull down assay, an increased
association of several proteins with ER was detected. The intensity of the ER
associated 45 kDa protein increased by 10-fold in the presence of 1000 microM
spermidine. These results indicate a specific role for spermidine in ER
association of proteins. Western blot analysis of samples eluted from GST-ER
showed the presence of chicken ovalbumin upstream promoter-transcription factor,
an orphan nuclear receptor, and the endogenous full-length ER. These results show
that multiple proteins associate with ER and that the binding of some of these
proteins is highly sensitive to intracellular polyamine concentrations. Overall,
our results indicate the importance of the polyamine pathway in the gene
regulatory function of estradiol in breast cancer cells.
PMID- 10194517
TI - Effect of insulin-like growth factor binding protein-1 on integrin signalling and
the induction of apoptosis in human breast cancer cells.
AB - Interaction of epithelial cells with the extracellular matrix is mediated through
integrin receptors, which transmit signals regulating cell growth,
differentiation and death. Occupation of these receptors, via Arg-Gly-Asp (RGD)
recognition sequences, leads to activation of focal adhesion kinase (FAK). We
treated human breast cancer cell lines with RGD-containing peptides, which can
disrupt integrin attachment, and investigated alterations in FAK phosphorylation,
cell detachment and death. Cells grown in vitro were treated with insulin-like
growth factor-binding protein-1 (IGFBP-1) and a small, synthetic RGD-containing
peptide (Gly-Arg-Gly-Asp-Thr-Pro) and its negative control peptide RGE (Arg-Gly
Glu-Ser) for either 30 min followed by immunoprecipitation of cell lysates with
anti-phosphotyrosine and Western immunoblotting with anti-FAK or for 24 h
followed by cell counting, immunocytochemistry and flow cytometry. Both IGFBP-1
(0-800 ng/ml) and the synthetic RGD-containing peptide (1-100 microg/ml) caused
significant dephosphorylation of FAK. Furthermore, after 24 h both peptides
caused detachment from the matrix and the induction of apoptosis. We conclude
from these data that IGFBP-1 can interact with integrin receptors to induce FAK
dephosphorylation and subsequently influence attachment and cell death.
PMID- 10194518
TI - Generating FSH antagonists and agonists through immunization against FSH receptor
N-terminal decapeptides.
AB - Follicle-stimulating hormone (FSH) via interaction with G-protein coupled
specific receptors plays a central role in the control of gametogenesis in
mammals of both sexes. In females, FSH is crucial for follicle growth, follicle
maturation and ovulation. FSH receptors, together with luteinizing hormone
chorionic gonadotropin and thyrotropin receptors belong to a subfamily of
structurally related receptors within the seven transmembrane receptor family.
Among several other regions, the N-terminus of these receptors is believed to be
responsible for important specific hormone-receptor contact sites. Recombinant
filamentous phages displaying at their surface three overlapping N-terminal
decapeptides of the FSH receptor, peptides A18-27, B25-34 and C29-38 were
constructed. Ewes and female mice were immunized against the three FSH receptor
(FSHR) recombinant phages. Immunoglobulins purified from immunized animals were
analyzed for their biochemical properties on a Chinese hamster ovary cell line
expressing the porcine FSH receptor. AntiA and antiB immunoglobulins (IgGs)
behave as antagonists for 125I-FSH binding and for FSH-dependent cAMP production,
while antiC IgGs did not compete for hormone binding. By contrast, antibodies
against the C29-38 peptide displayed FSH agonist activity and stimulated the FSH
receptor, whereas antiA and antiB IgGs did not. Furthermore, when the FSHR phages
were used as peptidic vaccines, they induced a reversible inhibition of ovulation
rate in ewes, and impaired fertility in female mice.
PMID- 10194519
TI - Gene expression of vasoactive intestinal contractor/endothelin-2 in ovary, uterus
and embryo: comprehensive gene expression profiles of the endothelin ligand
receptor system revealed by semi-quantitative reverse transcription-polymerase
chain reaction analysis in adult mouse tissues and during late embryonic
development.
AB - Vasoactive intestinal contractor (VIC)/endothelin-2 (ET-2) is a 21 amino acid
intestinal peptide characterized as a potent vasoactive and intestinal smooth
muscle-contracting compound. To investigate the physiological roles of VIC/ET-2
further, we characterized the specificity of VIC gene expression relative to that
of other members of the endothelin (ET) ligand-receptor system in adult mouse
tissues and during embryonic development. Gene expression of ET-1, ET-3, ETA and
ETB was ubiquitous in almost all tissues we examined while gene expression of VIC
was localized to certain tissues. A high level of VIC gene expression was
observed in ovary and uterus. The gene expression of VIC, relative to that of
glyceraldehyde-3-phosphate dehydrogenase, was approximately 2.0%, 0.4%, and 2.3%
in ovary, uterus, and intestine respectively, and was approximately 1.6 and 7. 1
times higher than that of ET-1 in ovary and intestine respectively. Thus, VIC may
have some physiological role in adult ovary and uterus as well as intestine. In
embryonic development, VIC gene expression sharply increased between 11 and 15
days post coitus and decreased after birth, suggesting an involvement in the
later stages of embryonic development.
PMID- 10194520
TI - Leptin signalling in pancreatic islets and clonal insulin-secreting cells.
AB - Leptin is a cytokine secreted from adipose tissue at a rate commensurate with the
size of the body's fat stores. In addition to its anorectic and thermogenic
central actions, leptin is known to act on peripheral tissues, including the
pancreatic beta-cell where it inhibits insulin secretion and reduces insulin
transcript levels. However, the role of leptin signalling through its full-length
receptor, OB-Rb, in the beta-cell remains unclear. In the present study, we show
that leptin activates a signal transducer and activator of transcription (STAT)3
signalling mechanism in pancreatic islets and in a rat model of the pancreatic
beta-cell, RINm5F. Leptin induced DNA binding to a STAT consensus oligonucleotide
and resulted in transcriptional activation from STAT reporter constructs in a
manner consistent with STAT3 activation. Western blot analysis confirmed
activation of STAT3 in RINm5F and isolated rat islets. Conditions that mimic
increased metabolic activity resulted in attenuation of leptin-mediated STAT DNA
binding but had no significant effect on STAT3 tyrosine phosphorylation in RINm5F
cells. In addition, leptin activated the mitogen activated protein (MAP) kinase
pathway in RINm5F cells. The present study provides a framework for OB-Rb
signalling mechanisms in the programming of the beta-cell by leptin and suggests
that increased metabolic activity may modulate this function.
PMID- 10194521
TI - The beta-subunit of human chorionic gonadotrophin exists as a homodimer.
AB - The free beta-subunit of human chorionic gonadotrophin (hCGbeta) is well
recognised as a product of many epithelial tumours. Recently, it has been shown
that this ectopic production may have a functional relationship to tumour growth.
The growth-promoting activity of hCGbeta may be explained by its structural
similarity to a family of growth factors which all contain the same distinct
topological fold known as the cystine-knot motif. Since the other members of this
family all exhibit their activities as homo- and heterodimers, it is possible
that the same may be true for hCGbeta. Using size-exclusion chromatography, low
stringency SDS-PAGE and matrix assisted laser desorption/ionisation (MALDI) time
of-flight (TOF) mass spectrometry (MS) we have shown that pure preparations of
hCGbeta contain hCGbetabeta homodimers. Size-exclusion chromatography revealed
asymmetric elution profiles with a forward peak corresponding to the size
exclusion characteristic of a globular protein with an approximate mass of 44-54
kDa and a late shoulder centered around an elution position expected for a
globular protein of approximately 29 kDa. Two immunoreactive hCGbeta species, of
approximately 32 and 64 kDa, were clearly resolved by SDS-PAGE and Western
blotting. When analysed by MALDI-TOF MS a |mf23 kDa monomer and a |mf46 kDa dimer
were identified. Formation of hCGbetabeta homodimers is consistent with the
behaviour of other cystine-knot growth factors and strengthens the inclusion of
the glycoprotein hormones within this superfamily. It has yet to be determined
whether it is this dimeric molecular species that is responsible for growth
promoting activity of hCGbeta preparations in tumours.
PMID- 10194522
TI - Amnion-derived cells express intercellular adhesion molecule-1: regulation by
cytokines.
AB - We have examined the expression of the intercellular adhesion molecule-1 (ICAM-1)
mRNA in primary and established amnion-derived cell cultures and regulation of
this expression by tumour necrosis factor-alpha (TNF-alpha) and interleukin (IL)
1beta. TNF-alpha (50 ng/ml) and IL-1beta (1.0 ng/ml) induced 18- and 11-fold
increases respectively in expression of the ICAM-1 mRNA in WISH cells (an amnion
epithelium-derived cell line). The increase was detectable within one hour of
treatment and peaked by two hours. The protein synthesis inhibitor, cycloheximide
(10 microg/ml) did not inhibit this induction. Increased levels of ICAM-1 protein
were detected in the cells within 4 h after initiation of treatment with either
cytokine. By 16 h of treatment with IL-1beta or TNF-alpha ICAM-1 reached 40 and
73 pg/microg cellular protein, representing 6- and 11-fold stimulations
respectively. In primary amnion cells, basal expression of ICAM-1 mRNA was
undetectable. However, TNF-alpha (50 ng/ml) induced ICAM-1 mRNA within two hours,
peak expression being reached between four and eight hours after initiation of
treatment. The present report demonstrates for the first time that amnion derived
cells can express ICAM-1 and, further, that this expression is regulated by pro
inflammatory cytokines. This has implications for the amnion as a possible source
for soluble ICAM-1, for this gene product as a marker for preterm labour, and for
participation of the amnion, additional to its reported secretory role, in
inflammatory processes of the fetal membranes.
PMID- 10194523
TI - IGFs and IGF-binding proteins in the regulation of human ovarian and endometrial
function.
PMID- 10194524
TI - Augmentation of diabetes-associated renal hyperfiltration and nitric oxide
production by pregnancy in rats.
AB - We tested the hypothesis that pregnancy might increase diabetes-associated nitric
oxide (NO) production and renal hyperfiltration. Two weeks following i.v.
streptozotocin (40 mg/kg), mean arterial pressure (MAP) was not modified by
diabetes; glomerular filtration rate (GFR), renal plasma flow (RPF) and
filtration fraction (FF) were higher in pregnant than in virgin controls and
increased by diabetes to a greater extent in pregnant than in virgin rats.
Urinary volume (UV), creatinine, albumin and sodium (UNaV) were significantly
increased by diabetes. Diabetes led to an increase in renal, cardiac, aortic and
uterine but not in placental NO synthase activities. Infusion of NG-nitro-l
arginine (l-NA) caused a dose-dependent reduction in GFR, RPF, plasma NO2-/NO3-,
UV and UNaV; in general, diabetes increased these effects to a greater extent in
pregnant than in virgin rats. l-NA increased MAP in all groups of rats but did
not alter FF. Diabetes did not alter responses of thoracic aorta rings to
vasoconstrictor effects of phenylephrine and the vasorelaxant effects of sodium
nitroprusside but increased endothelium-dependent relaxant effects of
acetylcholine. In general the effects of diabetes of 7 days duration were similar
to those described above for diabetes of 14 days duration. These data suggest
that diabetes-associated renal hyperfiltration and NO production are augmented by
pregnancy.
PMID- 10194525
TI - The influence of the colon on postprandial glucagon-like peptide 1 (7-36) amide
concentration in man.
AB - Glucagon-like peptide (7-36) amide (GLP-1) is an incretin hormone of the
enteroinsular axis released rapidly after meals despite the fact that GLP-1
secreting cells (L-cells) occur predominantly in the distal gut. The importance
of these colonic L-cells for postprandial GLP-1 was determined in healthy control
subjects and in ileostomy patients with minimal small bowel resection (<5 cm).
Subjects were fed a high complex carbohydrate test meal (15.3 g starch) followed
by two carbohydrate-free, high fat test meals (25 g and 48.7 g fat respectively).
Circulating levels of glucose, insulin, glucagon, glucose insulinotrophic peptide
(GIP) and GLP-1 were measured over a 9-h postprandial period. For both subject
groups the complex carbohydrate test meal failed to elicit a rise in either GIP
or GLP-1. However, both hormones were elevated after the fat load although the
GLP-1 concentration was significantly reduced in the ileostomist group when
compared with controls (P=0.02). Associated with this reduction in circulating
GLP-1 was an elevation in glucagon concentration (P=0.012) and a secondary rise
in the plasma glucose concentration (P=0.006). These results suggest that the
loss of colonic endocrine tissue is an important determinant in the postprandial
GLP-1 concentration. Ileostomists should not be assumed to have normal
enteroinsular function as the colon appears to have an important role in
postprandial metabolism.
PMID- 10194526
TI - Involvement of gonadal steroid hormone disturbance in altered prolactin receptor
gene expression in the liver of diabetic mice.
AB - The levels of mRNA for long and three short forms of prolactin receptor (PRLR)
were examined in the livers of normal (db+/db-) and insulin-resistant diabetic
(db+/db+) mice to assess the role of gonadal steroid hormones in the regulation
of PRLR gene expression in diabetes mellitus. In females, plasma levels of
testosterone in diabetic mice were higher, and those of 17beta-estradiol were
lower when compared with levels in normal mice. By contrast, diabetic male mice
had lower plasma levels of testosterone than normal males and showed no
significant difference in the low circulating level of 17beta-estradiol compared
with normal males. The short 3 form of PRLR (PRLR3) mRNA was the most abundant in
the liver of both normal and diabetic mice. In addition, the level of PRLR3 mRNA
in normal females was 8-fold higher than in normal males. The level of PRLR3 mRNA
in diabetic females was approximately a quarter lower than in normal females,
whereas the level of PRLR3 mRNA in diabetic males was approximately 2-fold higher
than in normal males. During postnatal development, the level of PRLR3 mRNA
increased during puberty in normal females, while the level in diabetic females
decreased to a nadir at 7 weeks of age followed by a progressive rise. On the
other hand, the levels of PRLR3 mRNA in both normal and diabetic males decreased
gradually during 5 to 14 weeks of age. Testosterone treatment of diabetic males
and females resulted in a 49.1 and 49.8% decrease of PRLR3 mRNA respectively.
17beta-Estradiol treatment slightly (18%) increased levels of PRLR3 mRNA in
diabetic males. These results suggest that the hepatic level of PRLR mRNA is
regulated by the inhibitory effect of testosterone and the stimulatory effect of
estrogen in both normal and diabetic mice.
PMID- 10194527
TI - Vascular endothelial growth factor gene and protein: strong expression in
thyroiditis and thyroid carcinoma.
AB - Angiogenesis is implicated in several pathological conditions, such as
inflammation and tumor growth. Vascular endothelial growth factor (VEGF), also
known as vascular permeability factor, is a potent stimulator of endothelial cell
proliferation in vitro and in vivo. The present work aimed to compare VEGF
expression in human normal thyroid glands, thyroiditis tissue and thyroid
carcinomas using immunohistochemistry and in situ hybridization (ISH). Both
chronic lymphocytic thyroiditis and differentiated thyroid carcinomas were found
to strongly express VEGF mRNA and encode larger amounts of VEGF than normal
thyroid tissue as attested by a VEGF immunostaining score. In addition, tumor
samples from patients with metastases showed a higher immunostaining score than
their non-metastatic counterparts (P<0.05). Carcinomas with the greatest contents
of VEGF mRNA and VEGF protein had the most intense mitogenic activity. Special
focus on endothelial cells showed intense mitogenic activity in neoplastic
tissues in contrast to the total quiescence of endothelial cells in non-tumoral
tissues. An intense VEGF production by differentiated thyroid carcinoma, attested
either by a higher immunostaining score or a strong VEGF mRNA expression using
ISH, could be a promising marker of tumor aggressiveness and may also be useful
as a predictor of metastatic potential.
PMID- 10194528
TI - Actions of vasoactive intestinal peptide on the rat adrenal zona glomerulosa.
AB - Previous studies, by this group and others, have shown that vasoactive intestinal
peptide (VIP) stimulates aldosterone secretion, and that the actions of VIP on
aldosterone secretion by the rat adrenal cortex are blocked by beta adrenergic
antagonists, suggesting that VIP may act by the local release of catecholamines.
The present studies were designed to test this hypothesis further, by measuring
catecholamine release by adrenal capsular tissue in response to VIP stimulation.
Using intact capsular tissue it was found that VIP caused a dose-dependent
increase in aldosterone secretion, with a concomitant increase in both adrenaline
and noradrenaline release. The effects of VIP on aldosterone secretion were
inhibited by atenolol, a beta1 adrenergic antagonist, but not by ICI-118,551, a
beta2 adrenergic antagonist. Binding studies were carried out to investigate VIP
receptors. It was found that adrenal zona glomerulosa tissue from control rats
contained specific VIP binding sites (Bmax 853+/-101 fmol/mg protein; Kd 2.26+/
0.45 nmol/l). VIP binding was not displaced by ACTH, angiotensin II or by either
of the beta adrenergic antagonists. The response to VIP in adrenals obtained from
rats fed a low sodium diet was also investigated. Previous studies have found
that adrenals from animals on a low sodium diet exhibit increased responsiveness
to VIP. Specific VIP binding sites were identified, although the concentration or
affinity of binding sites in the low sodium group was not significantly different
from the controls. In the low sodium group VIP was found to increase
catecholamine release to the same extent as in the control group, however, in
contrast to the control group, the adrenal response to VIP was not altered by
adrenergic antagonists in the low sodium group. These data provide strong support
for the hypothesis that VIP acts by the local release of catecholamines in
adrenal zona glomerulosa tissue in normal animals. It does not appear that VIP
acts through the same mechanism in animals maintained on a low sodium diet. The
mechanism by which VIP stimulates aldosterone in this group remains to be
determined.
PMID- 10194529
TI - Beta-cell gene expression and functional characterisation of the human insulinoma
cell line CM.
AB - Animal insulinoma cell lines are widely used to study physiological and
pathophysiological mechanisms involved in glucose metabolism and to establish in
vitro models for studies on beta-cells. In contrast, human insulinoma cell lines
are rarely used because of difficulties in obtaining and culturing them for long
periods. The aim of our study was to investigate, under different experimental
conditions, the capacity of the human insulinoma cell line CM to retain beta-cell
function, particularly the expression of constitutive beta-cell genes (insulin,
the glucose transporters GLUT1 and GLUT2, glucokinase), intracellular and
secreted insulin, beta-cell granules, and cAMP content. Results showed that CM
cells from an early-passage express specific beta-cell genes in response to
glucose stimulation, in particular the insulin and GLUT genes. Such capacity is
lost at later passages when cells are cultured at standard glucose
concentrations. However, if cultured at lower glucose concentration (0.8 mM) for
a longer time, CM cells re-acquire the capacity to respond to glucose
stimulation, as shown by the increased expression of beta-cell genes (insulin,
GLUT2, glucokinase). Nonetheless, insulin secretion could not be restored under
such experimental conditions despite the presence of intracellular insulin,
although cAMP response to a potent activator of adenylate cyclase, forskolin, was
present indicating a viable system. In conclusion, these data show that the human
insulinoma cell line CM, at both early-passage and late-passage, posseses a
functional glucose-signalling pathway and insulin mRNA expression similar to
normal beta-cells, representing, therefore, a good model for studies concerning
the signalling and expression of beta-cells. Furthermore, we have previously
shown that it is also a good model for immunological studies. In this respect it
is important to note that the CM cell line is one of the very few existing human
beta-cell lines in long-term culture.
PMID- 10194530
TI - Effects of ethanol on intraovarian nitric oxide production in the prepubertal
rat.
AB - Nitric oxide (NO) has been shown to contribute to ovarian development and
function. In non-ovarian tissues NO can be altered by ethanol (ETOH), a drug
considered to be a gonadal toxin in men as well as male and female rats. The
present study was undertaken to determine if some of the detrimental effects of
chronic ETOH exposure on prepubertal ovarian function could be due to ETOH
induced alterations in the intraovarian NO system. Rats were implanted with
intragastric cannulae on day 24 and began receiving control or ETOH diets on day
29. All rats were killed on day 34, determined to be in the late juvenile stage
of development, and their ovaries and blood were collected. We analyzed the
expression of the two constitutive forms of nitric oxide synthase (NOS), i.e.
neuronal (n) NOS and endothelial (e) NOS, as well as the inducible (i) form of
NOS protein in the ovaries of control and ETOH-treated rats by Western
immunoblotting. Results demonstrate that eNOS protein increased markedly (P<0.02;
140 kDa) in ETOH-treated rats compared with controls. ETOH treatment did not
alter the protein expression of nNOS (155 kDa) and only slightly increased that
of iNOS (130 kDa). We also assessed NOS activity as determined by nitrite
accumulation and by the conversion of L-[14C]arginine to L-[14C]citrulline. In
this regard, the ETOH-treated animals showed an increase in ovarian nitrite
generation (P<0.05), as well as an increase in ovarian citrulline formation
(P<0.0001), when compared with control animals. Along with the above described
ETOH-induced increases in ovarian eNOS and NO activity, the serum levels of
estradiol were concomitantly suppressed (P<0.001) in the ETOH-treated rats. These
results demonstrate for the first time the ETOH-induced changes in the
prepubertal ovarian NO/NOS system, and suggest that these alterations contribute
to the detrimental actions of the drug on prepubertal ovarian development and
function.
PMID- 10194531
TI - Differential expression of the growth hormone receptor and growth hormone-binding
protein in epithelia and stroma of the mouse mammary gland at various
physiological stages.
AB - Increasing evidence suggests that GH is important in normal mammary gland
development. To investigate this further, we studied the distribution and levels
of growth hormone receptor (GHR) and GH-binding protein (GHBP) in the mouse
mammary gland. At three weeks of age, the epithelial component of the right
fourth inguinal mammary gland of female mice was removed. These animals were then
either maintained as virgins until they were killed or they were mated. One group
of the mated mice was killed on day 18 of pregnancy and the remaining mated
animals were allowed to carry their pups until term and were killed on day 6 of
lactation. At the time of death, both the intact left and the de-epithelialized
right mammary glands were collected from all three groups. Some of the intact
glands served as a source of epithelial cells, free of stroma. The mRNA levels
for GHR and GHBP were measured in intact glands, epithelia-cleared fat pads, and
isolated mammary epithelial cells. GHR and GHBP mRNAs were expressed in both the
mammary epithelium and stroma. However, the levels of both GHR and GHBP mRNAs
were significantly higher in the stroma as compared with the epithelium
component. This increase for both mRNAs was from 3- to 12-fold at each
physiological state examined. In the intact gland, both GHR and GHBP transcripts
were highest in virgins, declined during late pregnancy, and the lowest levels
were found in the lactating gland. GHBP and GHR protein concentrations were also
assessed in intact glands and epithelia-free fat pads. Similar to the mRNAs, GHR
and GHBP protein levels (means+/-s.e.m.) in intact glands were highest in virgin
mice (0.891+/-0.15 pmoles/mg protein and 0.136+/-0.26 pmoles/mg protein
respectively), declined during late pregnancy (0. 354+/-0.111 pmoles/mg protein
and 0.178+/-0.039 pmoles/mg protein respectively), and were lowest during
lactation (0.096+0.037 pmoles/mg protein and 0.017+0.006 pmoles/mg protein
respectively). Immunocytochemistry utilizing specific antisera against mouse (m)
GHR and mGHBP revealed that the two proteins are localized to both the stroma and
parenchyma of mouse mammary glands, with similar patterns of immunostaining
throughout the different physiological stages analyzed. GHR immunolocalized to
the plasma membrane and cytosol of mammary epithelial cells and adipocytes,
whereas the GHBP immunostaining was nuclear and cytosolic. In conclusion, we
report here that GHR and GHBP mRNAs and proteins are expressed in both the
epithelium and the stroma of mammary glands of virgin, pregnant, and lactating
mice. In intact glands, GHR and GHBP proteins, as well as their transcripts are
higher in abundance in virgin relative to lactating mice. At all physiological
stages, GHR and GHBP mRNA levels are higher in the stroma compared with the
parenchyma. These findings indicate that the actions of GH in the mammary gland
are both direct through its binding to the epithelia, and indirect by binding to
the stroma and stimulation of IGF-I production which, in turn, affects mammary
epithelial development.
PMID- 10194532
TI - Modulation of rat preadipocyte adipose conversion by androgenic status:
involvement of C/EBPs transcription factors.
AB - Androgenic status affects rat preadipocyte adipose conversion from two deep intra
abdominal (epididymal and perirenal) fat depots differently. The aim of this
study was to establish whether these site-specific alterations of adipogenesis
are related to altered expressions of the transcriptional factors regulating
proliferation and differentiation of preadipocytes, c-myc and CCAAT/enhancer
binding proteins (C/EBPs: C/EBPalpha and beta). The increased proliferation of
epididymal and perirenal preadipocytes from castrated rats was not linked to
variations in c-myc mRNA and protein levels. The expression of the early marker
of adipogenesis, lipoprotein lipase (LPL), was decreased by androgenic
deprivation in epididymal cells but remained insensitive to the androgenic status
in perirenal preadipocytes. In contrast, LPL expression increased in subcutaneous
preadipocytes from castrated rats, an effect which was partly corrected by
testosterone treatment. Expression of C/EBPbeta was unaffected by androgenic
status whatever the anatomical origin of the preadipocytes. In contrast, the mRNA
and protein levels of C/EBPalpha were greatly decreased by androgenic deprivation
in epididymal cells, an alteration which could not be corrected by in vivo
testosterone administration. Altogether these results demonstrated that in
preadipocytes androgenic deprivation affects site-specifically the expression of
LPL, an early marker of adipogenesis and of C/EBPalpha, a master regulator of
adipogenesis. These observations contribute to an explanation of why castration
induces defective adipose conversion in rat epididymal preadipocytes
specifically.
PMID- 10194533
TI - Early pregnancy human chorionic gonadotropin (hCG) isoforms measured by an
immunometric assay for choriocarcinoma-like hCG.
AB - Human chorionic gonadotropin (hCG) exhibits molecular heterogeneity in both its
protein and carbohydrate moieties. This communication describes changes in hCG
isoforms detected directly in clinical samples. These isoforms, quantified in
blood or urine specimens, show a progression of change throughout normal
pregnancy. Early pregnancy produces a type of hCG that resembles, in terms of
immunoreactivity, a major form of hCG excreted in choriocarcinoma. The isoforms
predominate for the first 5-6 weeks of gestation and then diminish, being
replaced with the hCG isoforms which predominate throughout the remainder of
pregnancy. The alteration in hCG isoform content occurs in both blood and urine.
The progression of isoforms is best delineated by calculating the change in the
ratio of the two forms, as many hCG assays either do not detect or fail to
discriminate among these isoforms. An analogous pattern of hCG isoforms was
observed in patients with in vitro fertilization pregnancies. hCG isolated from
the pituitary displayed binding characteristics similar to those of the hCG
derived from normal pregnancy urine. The early pregnancy hCG isoforms appear to
have a differential expression in normal pregnancy as opposed to pregnancies
which will not carry to term, suggesting that a determination of the relative
balance of hCG isoforms may have diagnostic application in predicting pregnancy
outcome.
PMID- 10194535
TI - A negative iodine balance is found in healthy neonates compared with neonates
with thyroid agenesis.
AB - We studied the effects of the presence or absence of the thyroid gland on the
iodine metabolism and excretion in term Dutch newborns by performing a
retrospective study of the urinary iodine excretion in 193 term newborns with
abnormal congenital hypothyroidism screening results. Thirty-six euthyroid
newborns with decreased thyroxine-binding globulin levels were compared with 157
hypothyroid patients, 54 due to thyroid agenesis and 103 due to thyroid
dysgenesis. A significant difference in the urinary iodine excretion was observed
between the agenesis group (mean: 28 micrograms/24 h) and the euthyroid newborns
(mean: 46 micrograms/24 h, P=0.001). In conclusion, healthy, euthyroid, term
newborns excreted more iodine in their urine than newborns with thyroid agenesis.
These results strongly indicated the existence of a temporarily negative iodine
balance: the excretion of iodine prevailed over the intake and the newborn's
thyroidal iodine, stored during pregnancy, could be used for thyroxine synthesis
in the postnatal period. Since healthy term neonates were able to maintain
adequate plasma free thyroxine concentrations under normal TSH stimulation, the
prenatally acquired iodine stores could be considered sufficiently high to
compensate for the transient postnatal losses.
PMID- 10194534
TI - Comparison of mechanisms mediating uptake and efflux of thyroid hormones in the
human choriocarcinoma cell line, JAR.
AB - We compared the specificities of transport mechanisms for uptake and efflux of
thyroid hormones in cells of the human choriocarcinoma cell line, JAR, to
determine whether triiodothyronine (T3), thyroxine (T4) and reverse T3 (rT3) are
carried by the same transport mechanism. Uptake of 125I-T3, 125I-T4 and 125I-rT3
was saturable and stereospecific, but not specific for T3, T4 and rT3, as
unlabelled L-stereoisomers of the thyroid hormones inhibited uptake of each of
the radiolabelled hormones. Efflux of 125I-T3 was also saturable and
stereospecific and was inhibited by T4 and rT3. Efflux of 125I-T4 or 125I-rT3
was, in contrast, not significantly inhibited by any of the unlabelled thyroid
hormones tested. A range of compounds known to interfere with receptor-mediated
thyroid hormone uptake in cells inhibited uptake of 125I-T3 and 125I-rT3, but not
125I-T4. We conclude that in JAR cells uptake and efflux of 125I-T3 are mediated
by saturable and stereospecific membrane transport processes. In contrast, the
uptake, but not the efflux, of 125I-T4 and 125I-rT3 is saturable and
stereospecific, indicating that uptake and efflux of T4 and rT3 in JAR cells
occur by different mechanisms. These results suggest that in JAR cells thyroid
hormones may be transported by at least two types of transporters: a low affinity
iodothyronine transporter (Michaelis constant, Km, around 1 microM) which
interacts with T3, T4 and rT3, but not amino acids, and an amino acid transporter
which takes up T3, but not T4 or rT3. Efflux of T4 and rT3 appears to occur by
passive diffusion in these cells.
PMID- 10194536
TI - Is the primitive regulation of pituitary prolactin (tPRL177 and tPRL188)
secretion and gene expression in the euryhaline tilapia (Oreochromis mossambicus)
hypothalamic or environmental?
AB - We examined the effects of environmental salinity on circulating levels of the
two prolactins (tPRL177 and tPRL188) and levels of pituitary tPRL177 and tPRL188
mRNA in the euryhaline tilapia, Oreochromis mossambicus. Fish were sham-operated
or hypophysectomized and the rostral pars distalis (RPD) autotransplanted onto
the optic nerve. Following post-operative recovery in (1/4) seawater, tilapia
were transferred to fresh water (FW), (1/4) seawater (SW) or SW. Serum tPRL177
and tPRL188 levels in sham-operated and RPD-autotransplanted fish were highest in
FW and decreased as salinity was increased. tPRL177 and tPRL188 mRNA levels in
RPD implants as well as in pituitaries from the sham-operated fish were also
highest in FW and decreased with increasing salinity. Serum osmolality increased
with salinity, with the highest levels occurring in the seawater groups. We
conclude that some plasma factor (probably plasma osmolality), in the absence of
hypothalamic innervation, exerts a direct regulatory action on prolactin release
and gene expression in the pituitary of O. mossambicus. This regulation is in
accord with the actions of the two prolactins in the freshwater osmoregulation of
the tilapia.
PMID- 10194537
TI - Experimental cryptorchidism induces a change in the pattern of expression of LH
receptor mRNA in rat testis after selective Leydig cell destruction by ethylene
dimethane sulfonate.
AB - In the rat, the cytotoxic drug ethylene dimethane sulfonate (EDS) selectively
eliminates mature Leydig cells (LCs) from testicular interstitium, activating a
complex process of proliferation and differentiation of pre-existing LC
precursors. We observed previously that after EDS treatment, the early LC
precursors persistently express a truncated 1.8 kb form of LH receptor (LHR)
mRNA. This prompted us to study whether experimental cryptorchidism, known to
alter the process of LC repopulation, can influence the pattern of testicular LHR
mRNA expression after EDS administration. EDS treatment completely eliminated
mature LCs both in control and unilaterally cryptorchid (UC) rats. This response
was followed by gradual reappearance of newly formed, functionally active LCs, as
evidenced by the recovery in testicular LHR content and plasma testosterone
levels in both experimental groups. Noteworthy, the rate of LC repopulation was
higher in the abdominal testes of UC rats, in keeping with previous findings.
Interestingly, the 1.8 kb LHR transcript was persistently expressed in scrotal
testes at all time-points, but undetectable upon Northern hybridization in
abdominal testes at early stages after EDS administration, when low levels of
expression of truncated LHR transcripts could only be detected by semi
quantitative RT-PCR analysis. In addition, the faster LC repopulation in
cryptorchid testes was associated with precocious recovery of the complete array
of LHR mRNA transcripts, including the 1.8 kb species. These changes appeared
acutely and irreversibly, as unilateral positioning of scrotal testes into the
abdomen resulted in a rapid loss of expression of the 1.8 kb LHR transcript,
whereas scrotal relocation of the UC testes failed to alter the pattern of LHR
gene expression. In conclusion, experimental cryptorchidism changes the pattern
of LHR mRNA expression in rat testis after selective LC destruction by EDS. This
change, i.e. repression of the 1.8 kb LHR transcript after EDS administration, is
acute and irreversible, and likely related to the impairment of testicular
microenvironment following cryptorchidism. However, even though at low levels,
the expression of truncated forms of LHR mRNA appears to be a universal feature
of proliferating LC precursors. The UC testis may represent a good model for
analysis of the regulatory signals involved in the control of LHR gene
expression.
PMID- 10194538
TI - Oxytocin receptor expression in human term and preterm gestational tissues prior
to and following the onset of labour.
AB - Oxytocin receptor (OTR) mRNA expression has previously been demonstrated in human
myometrium, decidua, chorion and amnion but the effect of gestational age and the
onset of labour has not been determined in these individual tissues. Spatial OTR
mRNA expression was examined by in situ hybridization and ligand binding was
confirmed using autoradiography with the iodinated oxytocin antagonist
d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH29]-vasotocin (125I-OTA). Tissue was collected at
term (>37 weeks of gestation) or preterm (24-36 weeks of gestation) caesarean
section and classified as labour (contractions every 5 min associated with
cervical dilatation) or non-labour. OTR mRNA expression was measured as optical
density units from autoradiographs. There was a highly significant (P<0.001)
effect of tissue type on expression of OTR mRNA with expression greatest in
myometrium, low in decidua and chorion and not detected in placenta. Similar
results were obtained with the 125I-OTA-binding studies, indicating that the
message was translated. Amnion had an apparently high level of both hybridization
and 125I-OTA binding in some samples, but a lack of specificity prevented
quantification of the signal in this tissue type. Term myometrium (labour and non
labour) had significantly higher (P<0.01) OTR mRNA expression than preterm
myometrium, but there was no further increase in mRNA concentration associated
with labour onset. In contrast, 125I-OTA binding in myometrium was already high
at 33 weeks and did not increase further either later in pregnancy or with
labour. In decidua there was no effect of gestational age or labour onset on OTR
mRNA expression or 125I-OTA binding. In summary, OTR mRNA expression in the
myometrium increased in late pregnancy whereas decidual expression was much lower
and did not rise at term.
PMID- 10194539
TI - Insulin-like growth factors prevent cytokine-mediated cell death in isolated
islets of Langerhans from pre-diabetic non-obese diabetic mice.
AB - Interleukin-1beta (IL-1beta), tumour necrosis factor-alpha (TNF-alpha) and
interferon-gamma (IFN-gamma) contribute to the initial stages of the autoimmune
destruction of pancreatic beta cells. IL-1beta is released by activated
macrophages resident within islets, and its cytotoxic actions include a
stimulation of nitric oxide (NO) production and the initiation of apoptosis.
Insulin-like growth factors (IGFs)-I and -II prevent apoptosis in non-islet
tissues. This study investigated whether IGFs are cytoprotective for isolated
islets of Langerhans from non-obese diabetic mice (NOD) mice exposed to
cytokines. Pancreatic islets isolated from 5-6-week-old, pre-diabetic female NOD
mice were cultured for 48 h before exposure to IL-1beta (1 ng/ml), TNF-alpha (5
ng/ml), IFN-gamma (5 ng/ml) or IGF-I or -II (100 ng/ml) for a further 48 h. The
incidence of islet cell apoptosis was increased in the presence of each cytokine,
but this was significantly reversed in the presence of IGF-I or -II (IL-1beta
control 3.5+/-1.6%, IL-1beta 1 ng/ml 27.1+/-5.8%, IL-1beta+IGF-I 100 ng/ml 4.4+/
2.3%, P<0.05). The majority of apoptotic cells demonstrated immunoreactive
glucose transporter 2 (GLUT-2), suggesting that they were beta cells. Islet cell
viability was also assessed by trypan blue exclusion. Results suggested that
apoptosis was the predominant cause of cell death following exposure to each of
the cytokines. Co-incubation with either IGF-I or -II was protective against the
cytotoxic effects of IL-1beta and TNF-alpha, but less so against the effect of
IFN-gamma. Exposure to cytokines also reduced insulin release, and this was not
reversed by incubation with IGFs. Immunohistochemistry showed that IGF-I was
present in vivo in islets from pre-diabetic NOD mice which did not demonstrate
insulitis, but not in islets with extensive immune infiltration. Similar results
were seen for IGF-binding proteins (IGFBPs). These results suggest that IGFs
protect pre-diabetic NOD mouse islets from the cytotoxic actions of IL-1beta, TNF
alpha and IFN-gamma by mechanisms which include a reduction in apoptosis.
PMID- 10194540
TI - Somatostatin receptor subtype expression in cells of the rat immune system during
adjuvant arthritis.
AB - Somatostatin is a neuropeptide that is widely distributed throughout the body. It
acts as a neurohormone and a neurotransmitter and may also have an
immunomodulatory role. The genes for five subtypes of somatostatin receptors
(sst) have been cloned, suggesting that the diverse effects of the peptide might
be mediated by different receptors. We are interested in studying the role of sst
ininflammation, using an animal model. Because of the up-regulation of sst
expression in inflamed joints in human rheumatoid arthritis, we chose rat
adjuvant arthritis as an experimental model. In order to determine which of the
sst subtypes might be important in immune modulation, subtype expression in
leukocytes isolated from different lymphoid tissues of the rat was studied. Also,
the expression levels of the most abundantly expressed sst mRNAs in leukocytes
from spleen and blood were compared in rats with adjuvantarthritis and controls,
using a semi-quantitative approach. Furthermore, the effect of systemic
administration of a long-acting somatostatin analogue, octreotide, which binds
selectively to sst subtypes 2 and 5 (sst2 and sst5), on the incidence and the
severity of rat adjuvant arthritis, was studied. The main sst expressed in cells
of the rat immune system, both resting and activated, were found to be sst3 and
sst4. This contrasts with the human and murine situations, in which sst2 appears
to be the main subtype expressed in the immune system. No quantitative
differences in sst subtype mRNA levels in leukocytes from spleen and blood were
found between rats with adjuvant arthritis and controls. Finally, no effect of
systemic administration of octreotide on either the incidence or severity of
adjuvant arthritis in Lewis rats was found. As octreotide binds selectively to
sst2 and sst5, the absence of an immunomodulatory effect of this analogue in rat
adjuvant arthritis corroborates our finding that these sst subtypes are not
expressed in cells of the rat immune system. In conclusion, cells of the rat
immune system appear to express a spectrum of sst (sst3 and sst4) different from
that found in human granulomatous and autoimmune disease (mainly sst2).
Therefore, the rat adjuvant arthritis model appears to be suitable only for
studying the immunomodulatory effects of somatostatin analogues which have a high
affinity for sst3 and sst4, but not for studying the immunomodulatory effects of
octreotide, which has a high affinity only for sst2 and sst5.
PMID- 10194541
TI - Patients who are receiving concomitant medications should not systematically be
excluded from phase I studies.
AB - This retrospective study was designed to evaluate possible relationships between
the number and types of concomitant medications administered to patients on the
first day of therapy in phase I trials and demographic characteristics, outcome
measures and toxicities. Concomitant medications received by 690 patients
enrolled on 28 phase I trials between August 1985 and January 1996 were grouped
into 31 categories based on the American Hospital Formulary Service 1993. These
patients received 1650 cycles of treatment with investigational agents (median 2
cycles per patient). Median duration on-study was 49 days (range 1-776 days).
Clinical response rate (complete, partial, minor) was 3.8%. Only three toxic
deaths occurred (0.4%). Nearly all patients (90.9%) received at least one
concomitant medication on the first day of therapy. The number of concomitant
medications directly correlated with poor performance status (rSp = 0.27, p <
0.0001) and indirectly with duration on-study (rSp = -0.18, p < 0.0001). The dose
of the investigational agent administered during the first course of therapy was
not related to concomitant medications on the first day of therapy. Most
importantly, no relationships were observed between concomitant medications and
either toxicities or clinical response to therapy. We conclude that patients who
are receiving concomitant medications should not systematically be excluded from
phase I studies.
PMID- 10194542
TI - Sparse-data set analysis for irinotecan and SN-38 pharmacokinetics in cancer
patients co-treated with cisplatin.
AB - The clinical pharmacokinetics of the antineoplastic agent irinotecan (CPT-11) are
associated with substantial interpatient variability. The degree to which this
variability in CPT-11 exposure impacts upon the response and toxicity of the drug
has not yet been properly determined. In general, the area under the plasma
concentration-time curve (AUC) is an appropriate indicator of exposure, but
requires collection of up to 17 timed blood samples. This presents difficulties
if large-scale population samplings are required. The present study involved the
development and validation of a strategy to estimate the AUCs of the lactone and
total (i.e. lactone plus carboxylate) forms of CPT-11 and its active metabolite
SN-38 from a limited number of blood samples in patients co-treated with
cisplatin. Using data from 24 patients, univariate and multivariate regression
analyses were employed to generate the models. The best predictive models for
simultaneous estimation of CPT-11 and SN-38 AUCs were obtained with three time
points at 0.5, 1.67 and 5.50 h after start of the 90 min i.v. infusion of CPT-11.
The models were tested separately in another group of 24 patients receiving the
same combination treatment. This validation set demonstrated that CPT-11 and SN
38 AUCs after standard dose administration could be predicted sufficiently
unbiased and precisely with three timed samples to warrant clinical application.
PMID- 10194543
TI - Topoisomerase I/II inhibitor intoplicine administered as a 24 h infusion: phase I
and pharmacologic study.
AB - Intoplicine, an antitumor drug which interacts with both topoisomerase enzymes I
and II, has demonstrated a broad spectrum of activity in preclinical studies.
This indicates further clinical evaluation. In the present phase I study, with
the primary objective to determine the maximum tolerated dose, intoplicine was
administered by a 24 h continuous infusion every 21 days to 32 patients with
solid malignant tumors. The patients received 12-640 mg/m2 by a central venous
catheter. Liver toxicity was dose limiting. One patient died in a hepatic coma
after the first course (dose 640 mg/m2), which was associated with intoplicine
treatment. Other side effects were sporadic and mild. Myelotoxicity was virtually
absent. Twenty-two patients had stable disease for four to six courses of
treatment. The plasma concentration-time curves were compatible with standard
linear pharmacokinetic models, with a protracted terminal half-life (mean 115 h).
Although one sudden death occurred probably due to intoplicine toxicity, we
nevertheless feel that research with intoplicine should continue, mainly because
of its preclinical activity and its unique mechanism of action. The recommended
dose for phase II studies with intoplicine administered as a 24 h infusion is 384
mg/m2. Liver toxicity, also seen in studies employing other dosages and infusion
durations, should be investigated extensively in further clinical studies.
PMID- 10194544
TI - Prospective evaluation of high-dose ifosfamide-related nephrotoxicity in young
adult patients with recurrent osteosarcoma previously treated with cisplatin,
methotrexate and standard-dose ifosfamide.
AB - A prospective evaluation of high-dose ifosfamide (IFO)-related nephrotoxicity in
adults and young adults previously treated with cisplatin, methotrexate (MTX) and
standard-dose IFO was performed. Eighteen patients (median age 22) with recurrent
osteosarcoma were studied: 11 were pretreated with MTX, cisplatin and standard
dose IFO, and seven with MTX and cisplatin. The treatment was comprised of four
cycles of high-dose IFO (15 g/m2 over 5 days CI) and mesna at equivalent dose
with granulocyte colony stimulating factor support. Renal function was assessed
before treatment, after each IFO cycle and after chemotherapy completion. Acute
nephrotubular damage was always observed after each IFO cycle with significant
changes of renal tubular enzymes N-acetyl-beta-D-glucosaminidase, alanine
aminipeptidase, urinary excretion and reduction of tubular reabsorption of
phosphate. The appearance of glycosuria was related to the cumulative dose
received. Transient and reversible renal tubular acidosis was observed in three
patients. WHO grade I renal toxicity was observed in two patients. After
chemotherapy completion, persistent mild glomerular and nephrotubular impairment
was observed in one patient who had also received aminoglycoside antibiotics due
to febrile neutropenia. Persistent and mild glycosuria was documented in another
patient. No significant changes compared to baseline values were observed in the
remaining patients. We conclude that a chemotherapy regimen with high-dose IFO in
young adults pretreated with MTX, cisplatin and standard-dose IFO is feasible
with a mild, usually reversible, nephrotoxicity.
PMID- 10194545
TI - Impressive remission in a patient with locally advanced malignant pleural
mesothelioma treated with gemcitabine.
AB - The results of treatment of malignant pleural mesothelioma are quite
unsatisfactory regardless of the substance or schedule employed. Although some
activity is proved for anthracyclines, platinum compounds and alkylating
substances, no chemotherapeutic regimen has emerged as a standard of care.
Response rates documented in literature are between 10 and 20% for all these
regimens. We report about a patient with locally advanced, unresectable pleural
mesothelioma treated with the nucleoside analog gemcitabine (2,2
difluorodeoxycytidine). A 54-year-old male patient with unresectable pleural
mesothelioma confirmed by thoracoscopic biopsy was treated with seven cycles of
gemcitabine (1000 mg/m2 on day 1, 8 and 15) over a period of 36 weeks. Restaging
by thoracic computed tomography (CT) scan was performed after 8, 20 and 36 weeks.
At week 36 after beginning of treatment, the CT scan exhibited a substantial
partial remission with a reduction of tumor volume of over 50%. The adverse
effects of the therapy were very moderate with a hematotoxicity not exceeding WHO
grade I and a mild 'flu-like syndrome' during the first three cycles which
responded quite well to steroids. The compliance of the patient was excellent and
his general condition improved significantly under therapy. Gemcitabine seems to
be an active drug for the treatment of pleural mesothelioma. Compared to other
active regimens it is normally very well tolerated by the patients. Because of
these characteristics gemcitabine seems a suitable antineoplastic substance,
especially in palliative settings. It would be worthwhile to test its activity in
pleural mesotheliomas in controlled trials.
PMID- 10194546
TI - Makaluvamines vary in ability to induce dose-dependent DNA cleavage via
topoisomerase II interaction.
AB - The makaluvamines are marine natural products that were originally isolated
because of their cytotoxicity in a cell-based mechanism screen. They have
significant anti-cancer activity in animal models. There is, however,
disagreement in the literature as to whether these compounds target topoisomerase
II via a clinically relevant mechanism. This work shows that the makaluvamines
can induce dose-dependent DNA cleavage via topoisomerase II. For most of the
makaluvamines the levels of cleavage are significantly below those achieved by
equimolar concentrations of etoposide. To some extent these results might explain
the discrepancies present in the literature.
PMID- 10194547
TI - The cardioprotective and DNA topoisomerase II inhibitory agent dexrazoxane (ICRF
187) antagonizes camptothecin-mediated growth inhibition of Chinese hamster ovary
cells by inhibition of DNA synthesis.
AB - Dexrazoxane (ICRF-187), which is clinically used to reduce doxorubicin-induced
cardiotoxicity, has cell growth inhibitory properties through its ability to
inhibit the catalytic activity of DNA topoisomerase II. A study was undertaken to
investigate whether preincubating Chinese hamster ovary cells (CHO) with
dexrazoxane prior to camptothecin treatment resulted in potentiation.
Camptothecin is a DNA topoisomerase I poison. It was found that pretreating CHO
cells with concentrations of dexrazoxane sufficient to strongly inhibit
topoisomerase II for periods from 18 to 96 h resulted in significant antagonism
of camptothecin-mediated growth inhibition. Lower concentrations that were
sufficient to cause partial inhibition of topoisomerase II and partial
dexrazoxane-mediated cell growth inhibition had little effect on camptothecin
mediated growth inhibition. Neither topoisomerase I protein levels nor
camptothecin-induced topoisomerase I-DNA covalent complexes were affected by
dexrazoxane concentrations that were sufficient to cause antagonism of
camptothecin-induced growth inhibition. However, under these experimental
conditions, dexrazoxane caused a decrease in DNA synthesis. Therefore, results
presented here confirm the importance of the DNA synthesis-dependent replication
fork interaction with topoisomerase I-DNA covalent complexes for the expression
of camptothecin activity. It is concluded that dexrazoxane and camptothecin
analogs should be used with caution in combination chemotherapy.
PMID- 10194548
TI - Novel artificial endonucleases inhibit base excision repair and potentiate the
cytotoxicity of DNA-damaging agents on L1210 cells.
AB - A series of molecules with apurinic/apyrimidic (AP) endonuclease activity
targeted to abasic sites in DNA, which incorporate an intercalating moiety linked
to a purine base by a polyamino chain and recognize and cleave abasic sites in
DNA with high efficiency, has been studied. The aim was first to establish
whether these compounds were inhibitors of base excision DNA repair, since abasic
sites are generated during this process. Using an extension of a recently
established methodology, two members of this series have been identified as
definite repair inhibitors. Secondly, the potential of using such compounds as
sensitizers of alkylating agents has been investigated by determining the
cytotoxic activity of these compounds on L1210 cells in culture. A concentration
dependent potentiation of nitrosoureas has been demonstrated, but interpretation
is complicated by the inherent cytotoxic properties of the test compounds
themselves. Such molecules, however, provide interesting lead compounds for new
strategies aimed at enhancing the cytotoxic potential of clinically useful DNA
damaging agents.
PMID- 10194549
TI - Differential effects of UCN-01, staurosporine and CGP 41 251 on cell cycle
progression and CDC2/cyclin B1 regulation in A431 cells synchronized at M phase
by nocodazole.
AB - UCN-01 (7-hydroxystaurosporine) and CGP 41 251 (4'-N-benzoyl staurosporine), both
of which were discovered as protein kinase C selective inhibitors, have entered
in phase 1 clinical trials as anti-cancer drugs. In this study, we have directly
compared the effects of these drugs as well as staurosporine (STP) on cell cycle
progression of A431 human epidermoid carcinoma cells synchronized at M phase by
treatment with nocodazole. The nocodazole-synchronized cells progressed from M to
G1 phase in the absence of the drug, which was accompanied by a decrease of
cyclin B1 protein expression, disappearance of the complex formation of CDC2 with
cyclin B1 and reduction of the kinase activity. Treatments of the M phase cells
with UCN-01, STP and CGP 41 251 at 80% growth-inhibitory concentrations (IC80S)
resulted in specific G1 block, G2M block and polyploidy, respectively. Decreases
of cyclin B1 protein expression was partially prevented by treatments with STP
and CGP 41 251 but not with UCN-01 at IC80S. Reductions of active complex and
kinase activity of CDC2/cyclin B1 were also observed in the presence of the three
drugs. In addition, augmentation of CDC2 protein tyrosine phosphorylation was
induced only when the cells were treated with STP. These observations
demonstrated that higher concentrations of UCN-01, STP and CGP 41 251 showed
different effects on cell cycle progression as well as CDC2/cyclin B1 regulation
in A431 cells synchronized at M phase. The data suggest that UCN-01 and CGP 41
251 may act at quite different points on the cell cycle.
PMID- 10194550
TI - Pharmacokinetics and central nervous system toxicity of declopramide (3
chloroprocainamide) in rats and mice.
AB - Declopramide (3-chloroprocainamide) has been identified in previous studies as a
representative of a new class of chemosensitizers. In this study, the toxicity
and pharmacokinetics of declopramide have been investigated and compared with a
structural analog, metoclopramide (MCA). Declopramide has not induced central
nervous system (CNS)-related side effects in rats at doses up to 200 mg/kg,
whereas MCA does at 12.5 mg/kg. In addition, declopramide did not bind to
dopamine D2 receptors in subcellular preparations at doses up to 100 microM,
whereas MCA showed affinity at 1 microM. Declopramide bound with affinity to 5
hydroxytryptamine3 receptors which are important in controlling vomiting. In
contrast to MCA, declopramide has a rapid clearance from serum, a lower tissue
concentration (about 15-fold lower than MCA) and a lower oral bioavailability
(about 6-fold lower than MCA). However, declopramide was shown in vitro to
possess a higher tumor cell absorption rate. One of the main metabolites of
declopramide was identified as N-acetyl declopramide. Taken together, these data
suggest that the clinical development of declopramide as a sensitizer of radio-
and chemotherapies is an improvement over MCA, because it can be administered in
a high dose and is devoid of CNS side effects.
PMID- 10194551
TI - Biodistribution and scintigraphy of [111In]DTPA-adriamycin in mammary tumor
bearing rats.
AB - The aim of this study was to develop an 111In-labeled diethylenetriamine
pentaacetic acid-adriamycin (DTPA-ADR) conjugate to image breast cancer. DTPA-ADR
was synthesized by reacting adriamycin with DTPA anhydride in the presence of
carbonyldiimidazole. After dialysis (MW cut off was 500), the product was freeze
dried (yield 40-50%). An in vitro cell culture study was performed using cells
from the 13,762 Fischer rat mammary tumor line. Drug concentrations tested were
0.1-100 microM. Biodistribution studies were conducted at 0.5, 2, 24 and 48 h in
mammary tumor-bearing rats (n = 3/time interval, 10 microCi/rat, i.v.) with
13,762 cells (10(5) cells/rat, s.c.). Planar imaging and autoradiograms were
obtained at the same intervals. In vitro cell culture assays showed an IC50 of
0.1 +/- 0.01 microM for ADR and 7.2 +/- 0.29 microM for DTPA-ADR, respectively.
In biodistribution studies, tumor/blood uptake ratios of [111In]DTPA-ADR at 0.5,
2, 24 and 48 h were 0.55 +/- 0.17, 0.94 +/- 0.17, 3.06 +/- 0.53 and 3.66 +/-
0.35, respectively, whereas those for [111In]DTPA (control) were 1.19 +/- 0.69,
0.84 +/- 0.07, 0.56 +/- 0.10 and 0.60 +/- 0.03, respectively. The tumor uptake
value (%ID/g) of [111In]DTPA-ADR at 0.5 h was 0.20 +/- 0.06. Planar images and
autoradiograms showed good visability of tumors. Biodistribution, autoradiography
and radionuclide imaging of [111In]DTPA-ADR in breast tumor-bearing rats showed
that tumor-to-blood ratios increased steadily between 30 min and 48 h. These
results indicate that DTPA-ADR, a new cancer imaging agent, might be useful in
the diagnosis of breast cancer and may predict a therapeutic effect prior to
treatment.
PMID- 10194552
TI - Recombinant human interleukin-11 is unlikely to stimulate the growth of the most
common solid tumors.
AB - Recombinant human interleukin-11 (rhIL-11) has been shown to enhance recovery
from thrombocytopenia and mucosal injury after cancer chemotherapy. Since RNA for
the receptor and signal transducer for IL-11 is detected in many cell types
including some cancer cells, it was theoretically possible that rhIL-11 could
affect the growth of tumor cells. This study was intended to determine whether
rhIL-11 stimulates the proliferation of human tumor colony-forming units (TCFUs)
taken directly from patients. Tumor cells were cultured in soft agar and
continuously exposed to three concentrations of rhIL-11 (1.0, 10.0 and 100.0
U/ml) for 14 days in the capillary cloning system. Growth stimulation was noted
in two of 66 (3%) of evaluable specimens, including one of 14 evaluable non-small
cell lung cancer and one of five evaluable colon cancer specimens. In these two
specimens, there was no increased stimulation of TCFUs with escalating
concentrations of rhIL-11. Interestingly, the highest concentration of rhIL-11
tested inhibited the growth of 16 specimens (24.2%; 95% confidence interval 13.9
34.5%). Growth inhibition demonstrated a concentration-response relationship (p <
0.001). These results suggest that rhIL-11 appears unlikely to stimulate the
growth of the most common solid tumors.
PMID- 10194553
TI - Effects of methylacetylenic putrescine, an ornithine decarboxylase inhibitor and
potential novel anticancer agent, on human and mouse cancer cell lines.
AB - Sensitivity of several human and mouse cancer cell lines to methylacetylenic
putrescine (MAP) was evaluated using clonogenic, sulforhodamine B and cell
counting assays. The effects of MAP on cell morphology, cell cycle phase
distribution and changes in polyamine metabolism of xenografted MCF-7 and MDA-MB
231 human mammary tumor cells were also investigated. On the basis of IC50
values, BHT-101 human thyroid carcinoma cells were the most sensitive (9
micrograms/ml), followed by P388 mouse lymphoma (32 micrograms/ml), MCF-7 (48
micrograms/ml) and MDA-MB-231 (110 micrograms/ml) human breast carcinoma cell
lines. MAP treatment led to accumulation of P388 cells in G1 phase. At higher
doses, the cytoplasm of the cells became vacuolated followed by apoptosis. The
foamy cytoplasm may suggest a rare type of cell death (Clarke III type) called
non-apoptotic programmed cell death. MAP treatment resulted in a total inhibition
of ornithine decarboxylase (ODC) activity with a concomitant decrease of
intracellular polyamine (mostly putrescine and spermidine) content in the breast
cancer cells, whilst the spermine concentration was shown to increase. MAP proved
at least 10 times more potent than the formerly studied DL-alpha
difluoromethylornithine making it an attractive candidate for clinical testing.
PMID- 10194554
TI - Growth inhibitory effect of L-canavanine against MIA PaCa-2 pancreatic cancer
cells is not due to conversion to its toxic metabolite canaline.
AB - L-Canavanine (CAV) is an arginine (ARG) analog isolated from the jack bean,
Canavalia ensiformis. CAV becomes incorporated into cellular proteins of MIA PaCa
2 human pancreatic cancer cells and the aberrant, canavanyl proteins are not
preferentially degraded. Hydrolytic cleavage of CAV to canaline (CAN) and urea is
mediated by arginase. CAN is a potent metabolite that inactivates vitamin B6
containing enzymes and may inhibit cell growth. To determine the presence of
arginase and its specificity for ARG and CAV in MIA PaCa-2 cells, a radiometric
assay, which quantifies the 14C released from the hydrolytic cleavage of L
[guanidino-14C]ARG or L-[guanidinooxy-14C]CAV mediated by arginase, was employed.
Insignificant amounts of 14CO2 were released when cells were exposed to [14C]CAV
or to [14C]ARG. Pancreatic cancer cells secrete a negligible amount of arginase.
Cytotoxic effects of CAN and CAV were compared on cells exposed to varying
concentrations of ARG. These studies provide evidence that CAV's cytotoxic
effects on MIA PaCa-2 cells cannot be attributed to conversion to the active
metabolite CAN. A slower and decreased hydrolysis of CAV by arginase allows CAV
to persist and increases its chances of incorporating into proteins in these
cells. Lack of considerable amounts of arginase in the pancreas makes CAV a
worthy candidate for further studies in pancreatic cancer.
PMID- 10194555
TI - Effect of vesnarinone in combination with anti-cancer drugs on lung cancer cell
lines.
AB - Vesnarinone, a quinolinone derivative which is used as an oral inotropic agent in
the clinic, has recently also been shown to have anti-cancer activity. We have
studied the anti-cancer effect of vesnarinone in combination with cisplatin, VP
16 (etoposide) and gemcitabine, against human lung cancer cell lines (PC-9 and Lu
134A) using the MTT assay and isobologram analysis. Simultaneously, by
establishing two cisplatin-resistant sublines, i.e. PC-9/CDDP and Lu 134A/CDDP,
we analyzed the cross-resistance between vesnarinone and cisplatin and the
resistance-reversing effect of vesnarinone. Nuclear fragmentation, as the
presumed mechanism of tumor cell growth inhibition, was further studied
quantitatively using flow cytometric analysis. Combination of vesnarinone with
the studied anti-cancer drugs had a synergic or additive inhibitory effect on
both PC-9 and Lu 134A tumor cell growth. Neither decrease of the sensitivity to
vesnarinone nor cross-resistance between vesnarinone and anti-cancer drugs was
observed. On the contrary, vesnarinone showed a resistance-reversing effect. Both
vesnarinone and the studied anti-cancer drugs could induce tumor cell apoptosis,
but a definite correlation between nuclear fragmentation and the growth
inhibitory effect was not established.
PMID- 10194556
TI - Reduction of lung metastasis by ImH[trans-RuCl4(DMSO)Im]: mechanism of the
selective action investigated on mouse tumors.
AB - NAMI-A (imidazolium trans-imidazoledimethylsulfoxidetetrachlororuthenate,
ImH[trans-RuCl4(DMSO)Im]) is a new ruthenium compound active against lung
metastasis of solid metastasizing tumors. We have tested this compound in mice
with Lewis lung carcinoma or MCa mammary carcinoma in order to compare the
effects on primary tumor and lung metastases with possible alterations of cell
cycle distribution of tumor cells. We have also investigated whether there were
unequal tissue accumulations of the compound itself at different dose levels
ranging from 17.5 to 70 mg/kg/day given for six consecutive days. NAMI-A caused a
reduction of metastasis weight larger than that of metastasis number; we explain
this finding as the capacity of NAMI-A to selectively interfere with the growth
of metastases already settled in the lungs. However, this specificity is not
simply related to a larger concentration of NAMI-A in the lungs than in other
tissues. Following i.p. treatment, NAMI-A rapidly disappeared from the peritoneal
cavity; its low blood concentration may be caused by rapid renal clearance. These
data provide further evidence for a selective anti-metastasis effect of the
ruthenium complex NAMI-A. The reduction of lung metastasis is followed by a
significant prolongation of the host's life-time expectancy, indicating a
therapeutic benefit of NAMI-A on lung metastases from solid tumors.
PMID- 10194557
TI - Interaction of static and extremely low frequency electric and magnetic fields
with living systems: health effects and research needs.
AB - An international seminar was held June 4-6, 1997, on the biological effects and
related health hazards of ambient or environmental static and extremely low
frequency (ELF) electric and magnetic fields (0-300 Hz). It was cosponsored by
the World Health Organization (WHO), the International Commission on Non-Ionizing
Radiation Protection (ICNIRP), the German, Japanese, and Swiss governments.
Speakers provided overviews of the scientific literature that were discussed by
participants of the meeting. Subsequently, expert working groups formulated this
report, which evaluates possible health effects from exposure to static and ELF
electric and magnetic fields and identifies gaps in knowledge requiring more
research to improve health risk assessments. The working groups concluded that,
although health hazards exist from exposure to ELF fields at high field
strengths, the literature does not establish that health hazards are associated
with exposure to low-level fields, including environmental levels. Similarly,
exposure to static electric fields at levels currently found in the living and
working environment or acute exposure to static magnetic fields at flux densities
below 2 T, were not found to have demonstrated adverse health consequences.
However, reports of biological effects from low-level ELF-field exposure and
chronic exposure to static magnetic fields were identified that need replication
and further study for WHO to assess any possible health consequences. Ambient
static electric fields have not been reported to cause any direct adverse health
effects, and so no further research in this area was deemed necessary.
PMID- 10194558
TI - Biphasic effects of static magnetic fields on cutaneous microcirculation in
rabbits.
AB - The biphasic effects of locally applied static magnetic fields (SMF) on the
cutaneous microcirculation within a rabbit ear chamber (REC) were evaluated under
conscious conditions. The microcirculatory vasomotion within a REC was measured
continuously and analyzed multilaterally by microphotoelectric plethysmography, a
real-time image analyzer and an image shearing monitor. SMF intensities at the
REC were controlled at 1 mT and the duration of exposure was 10 min. Seventy
eight experimental trials were carried out on 22 healthy adult rabbits weighing
2.6-3.5 kg. Five experimental groups were chosen at random: 1) no pharmacological
treatment or SMF exposure, 2) increased vascular tone induced by noradrenaline
infusion without SMF exposure, 3) increased vascular tone induced by
noradrenaline infusion with SMF exposure, 4) decreased vascular tone induced by
acetylcholine infusion without SMF exposure, 5) decreased vascular tone induced
by acetylcholine infusion with SMF exposure. The results demonstrated that SMF
significantly enhanced vasodilatation, with increased vasomotion under
noradrenaline-induced high vascular tone as well as vasoconstriction with reduced
vasomotion under acetylcholine-induced low vascular tone. This suggests,
therefore, that SMF can modulate vascular tone due to biphasic modification of
vasomotion in the cutaneous tissue.
PMID- 10194559
TI - Different effects of microwave energy and conventional heat on the activity of a
thermophilic beta-galactosidase from Bacillus acidocaldarius.
AB - The effect of microwave (f = 10.4 GHz) irradiation on a thermostable enzyme was
experimentally tested, showing that irreversible inactivation is obtained.
Enzymatic solutions (500 microliters, with concentrations between 10-100
micrograms/ml) were exposed at 70 degrees C, at SAR levels of 1.1 and 1.7 W/g for
15, 30, 45, or 60 min, and their activity was compared to that of a sample heated
in a water bath at the same temperature. The residual activity of the exposed
samples depends on enzyme concentration, microwave power level, and exposure
time; activity was reduced to 10% in 10 micrograms/ml solutions treated at 1.7
W/g for 60 min. Microwave effects disappeared at concentrations above 50
micrograms/ml. These results were not found following water bath heating at the
same temperature and durations.
PMID- 10194560
TI - Correlation between pulsed electromagnetic fields exposure time and cell
proliferation increase in human osteosarcoma cell lines and human normal
osteoblast cells in vitro.
AB - We have exposed cultured bone cells to a pulsed electromagnetic field (PEMF) for
different times to find the minimal exposure time necessary to stimulate an
increase of DNA synthesis. We used two different human osteosarcoma cell lines,
TE-85 and MG-63, and human normal osteoblast cell (NHOC) obtained from surgical
bone specimens. The cells were placed in multiwell plates and set in a tissue
culture incubator between a pair of Helmoltz coils powered by a pulse generator
(1.3-ms pulse, repeated at 75 Hz) for different periods of time. [3H]Thymidine
incorporation was used to evaluate cell proliferation. The two osteosarcoma cell
lines increase their thymidine incorporation when exposed to a PEMF for at least
30 min, both in a medium containing 10% fetal calf serum and in a serum-free
medium. NHOC are known to increase their cell proliferation when exposed to PEMF
but only if cultured in the presence of 10% fetal calf serum. In this
experimental condition, three of the four cell lineages studied required at least
9 h of PEMF exposure to increase their DNA synthesis, whereas one cell lineage
increased its cell proliferation after 6 h of PEMF exposure. Our observations
confirm the hypothesis that the proliferative responses of NHOC and human
osteosarcoma cell lines to PEMF exposure are quite different. Moreover, NHOC
required minimal exposure times to PEMF to increase their cell proliferation,
similar to that needed to stimulate bone formation in vivo.
PMID- 10194561
TI - Simplified model and measurement of specific absorption rate distribution in a
culture flask within a transverse electromagnetic mode exposure system.
AB - In vitro experiments in bioelectromagnetics frequently require the determination
of specific absorption rate (SAR) within a layer of cells on the bottom of a
culture flask when the SAR has rapid spatial variation both horizontally within
the cell layer and vertically in the medium bathing the cells. This problem has
only recently been treated in the literature; and it is here approached
differently for another irradiation system. It is shown that a simple two
dimensional frequency-domain guided-wave treatment yields results qualitatively
comparable to those of more computationally intensive three-dimensional time
domain free-field scattering treatments. The problem of inferring local SARs from
temperature-vs.-time curves is shown to be seriously confounded by thermal
diffusion; and specific analytic and numerical results are presented to aid in
understanding this effect. A novel experimental technique is introduced for
measuring millikelvin temperature offsets with subsecond resolution, and
illustrative experimental data are presented. Finally, present experimental and
theoretical uncertainties are considered; and it is pessimistically asserted
that, in a culture flask where spatial SAR variation is rapid, point SAR
measurements by thermal methods may be in error by as much as +/- 3 dB. More
reliable thermal determinations will require extreme care, challenging
technological innovations, or both.
PMID- 10194562
TI - Kinetics of sealing for transient electropores in isolated mammalian skeletal
muscle cells.
AB - Permeabilization of the plasma membrane by electrical forces (electroporation)
can be either transient or stable. Although the exact molecular mechanics have
not yet been described, electroporation is believed to initiate primarily in the
lipid bilayer. To better understand the kinetics of membrane permeabilization, we
sought to determine the time constants for spontaneous transient pore sealing. By
using isolated rat flexor digitorum brevis skeletal muscle cells and a two
compartment diffusion model, we found that pore sealing times (tau p) after
transient electroporation were approximately 9 min. tau p was not significantly
dependent on the imposed transmembrane potential. We also determined the
transmembrane potential (delta Vm) thresholds necessary for transient and stable
electroporation in the skeletal muscle cells. delta VmS ranging between 340 mV
and 480 mV caused a transient influx of magnesium, indicating the existence of
spontaneously sealing pores. An imposed delta Vm of 540 mV or greater led to
complete equilibration of the intracellular and extracellular magnesium
concentrations. This finding suggests that stable pores are created by the larger
imposed transmembrane potentials. These results may be useful for understanding
nerve and skeletal muscle injury after an electrical shock and for developing
optimal strategies for accomplishing transient electroporation, particularly for
gene transfection and cell transformation.
PMID- 10194563
TI - Designing medical devices to reduce the likelihood of error.
PMID- 10194564
TI - Equipment management risk rating system based on engineering endpoints.
AB - The equipment management risk ratings system outlined here offers two significant
departures from current practice: risk classifications are based on intrinsic
device risks, and the risk rating system is based on engineering endpoints.
Intrinsic device risks are categorized as physical, clinical and technical, and
these flow from the incoming equipment assessment process. Engineering risk
management is based on verification of engineering endpoints such as clinical
measurements or energy delivery. This practice eliminates the ambiguity
associated with ranking risk in terms of physiologic and higher-level outcome
endpoints such as no significant hazards, low significance, injury, or mortality.
PMID- 10194565
TI - Home health care: a new challenge for clinical engineers.
PMID- 10194566
TI - Meeting the requirements for medical equipment EMC: a test house perspective.
PMID- 10194567
TI - The physiologic and medical rationale for intrapartum fetal monitoring.
AB - In the United States and most industrialized countries, intrapartum fetal
surveillance is performed primarily by electronic fetal heart rate monitoring.
Following implementation of this technology into clinical practice, a reduction
in perinatal mortality has been accompanied by a concomitant increase in the
cesarean section rate to concerning levels. Although these trends are not solely
due to one factor such as electronic fetal heart rate monitoring, it is well
recognized that this method of surveillance is hampered by subjectivity in
interpretation and by a high false-positive (falsely nonreassuring) rate. The
purpose of this review is to assess the physiologic rationale for intrapartum
assessment, the significant limitations of current primary and ancillary
monitoring methods, and the development of new technologies such as fetal oxygen
saturation monitoring (pulse oximetry) that potentially hold great promise for
the future.
PMID- 10194569
TI - How do transitional objects work?: the therapist's view.
AB - Research into the use of transitional objects (Winnicott, 1971) by adult clients
in psychotherapy has given little attention to the question of how a transitional
object (TO) works. This question is addressed through the use of a semi
structured interview. Data was collected on the clinical practice and theoretical
understanding of TO emergence and use of three psychodynamic-interpersonal (PI)
and three Gestalt psychotherapists. A grounded theory analysis suggests that a TO
works by a process of embodiment which can be structured with reference to a four
level model consisting of physical, process, contextual and conceptual levels.
Therapists of both orientations emphasized the TO as a focus of intersubjectivity
within the therapeutic relationship. Differences between the PI and Gestalt
therapists are also examined. The clinical implications of this four-level model
of embodiment for the use of TOs in psychotherapy are explored, together with
suggestions for further research.
PMID- 10194568
TI - Chronomes, time structures, for chronobioengineering for "a full life".
AB - Week-long or longer monitoring of blood pressure and heart rate, coupled to time
structure analyses, can help detect disease-risk elevations, as a warning of the
need for a preventive prehabilitation. Within the normal range of physiologic
variation, computer methods quantify time structures, or chronomes, that can
serve as reference values. The major applied purpose for mapping chronomes is the
detection of disease-risk syndromes such as blood pressure "overswinging" and
heart rate "underswinging." Too much blood pressure variability (circadian
hyperamplitude tension; CHAT), is a risk factor for vascular disease. Other risk
syndromes are chronome alterations of heart rate variability (CAHRVs), consisting
of a loss of "jitter", i.e., a reduced standard deviation of heart rate or of
alterations in the spectral element of the heart-rate-variability chronome, such
as in the correlation dimension, an endpoint of deterministic chaos. These
alterations can again serve for prehabilitation. On the basic side, the spectral
element of the heart-rate-variability chronomes extends from focus on the
heartbeat's period of about 1 second to periods in heart rate and its standard
deviation that are numerical equivalents of about 10.5- and about 21-year cycles
of solar activity. A seemingly unnatural physiologic rhythm or pattern (such as
one of 81.6 hours) may correspond numerically to a purely physical environmental
rhythm. For example, interplanetary magnetic storms, with their cycles as
external chronome components, trigger myocardial infarctions, strokes, and
traffic accidents. The systematic monitoring of external rhythms along with
physiologic ones for the concurrent analysis of rhythms with longer and longer
periods could detect alterations anywhere in and between the 1 cycle/sec and the
1 cycle/10.5- or 21-years regions of the spectrum. Chronobiomimetic engineering
for discovering both instantaneous and long-term chronorisk alterations can
provide warnings of increased risk. If risk-lowering therapy is then instituted
automatically, instrumented health care will be extended beyond the pacemaker
cardioverter-defibrillator, which focuses on the frequency of 1 cycle/sec.
Instrumentation that automatically detects blood pressure that varies too much
and heart rate that varies too little is needed for prompting prophylactic CHAT
and CAHRV treatment. A database of reference values that can be used for
chronodiagnosis is now accumulating.
PMID- 10194570
TI - Detecting complex patterns in interpersonal profiles.
AB - The assessment of interpersonal problems has advanced in recent years with the
development of new methods for analysing individual profiles. These new methods
assume that each profile can be modelled by a mathematical function that reflects
the person's single prevailing interpersonal theme. However, some profiles may
contain more complex patterns, with two or more distinct themes. Such
complexities in a person's interpersonal profile might be clinically important,
perhaps reflecting an interpersonal style that is conflictual. In an effort to
detect complex patterns, Fourier analysis was applied to profiles of 200
psychotherapy out-patients and 200 undergraduates, using the Inventory of
Interpersonal Problems. Although many profiles did not clearly manifest a single
prevailing interpersonal theme, having two distinct profile peaks, their apparent
complexity generally resulted from measurement error. Systematically complex or
conflictual patterns were rarely detectable. Profiles of interpersonal problems
may contain complex patterns, but simple patterns reflecting the prevailing
interpersonal theme are apt to be more clinically informative.
PMID- 10194571
TI - Multidimensional scaling analysis of paranoid symptoms in the context of
depressive and psychotic disorders.
AB - The present study examined a continuum of paranoid symptoms in the context of
depressive and psychotic disorders from a multidimensional perspective on
psychopathology. Based on the self-ratings of 404 community residents, 96
depressed patients, and 65 psychotic patients, similarities or dissimilarities
among multiple measures of paranoia (i.e. mild, moderate, and severe types),
along with 16 other psychiatric symptom scales taken from the Psychiatric
Epidemiology Research Interview (PERI; Dohrenwend, Shrout, Egri & Mendelsohn,
1980, Dohrenwend, Levav & Shrout, 1986b, were analysed using multidimensional
scaling supplemented by cluster analysis. Four hypotheses were tested. Only one
hypothesis was fully supported and two were partially supported. No distinct
dimension for the continuum of paranoia emerged, but a global dimension of
severity of psychopathology was pervasive and stable across diagnostic subgroups.
The latter finding replicated and extended previous multidimensional studies of
psychopathology.
PMID- 10194572
TI - Designing response scales for cross-cultural use in health care: data from the
development of the UK WHOQOL.
AB - Designing response scales for use in cross-cultural situations presents several
semantic and conceptual challenges. Here we report response scales designed in
the UK, using a method developed collaboratively by the WHOQOL Group to tackle
some of these issues. The response scales were generated for use with items
established for a British version of a new cross-cultural quality of life measure
for health and health care--the UK WHOQOL. A quota sample of 20 sick and well
people assigned 60 descriptions to separate 100 mm lines (15 for each of 4 types
of response scale) where the polar anchor points had been internationally agreed
as meaningful in 10 countries. Means and standard deviations (SD) were calculated
for each label appropriate to that response scale. The closest mean and smallest
SD earmarked labels for each type of scale at the 25%, 50% and 75% interval. This
research provides a set of contemporary, 5-point interval response scales that
have the potential to be used in any number of British health and health-care
questionnaires where subjective measures are needed.
PMID- 10194573
TI - Transference--counter-transference constellations and enactments in the
psychotherapy of destructive narcissism.
AB - Destructive narcissism, characterized by a perverse alliance between the self and
an omnipotent bad internal object, constitutes a serious obstacle to
psychoanalytic psychotherapy. This paper draws together various object relations
theories of destructive narcissism, and presents a case study of a failed
psychotherapy to illustrate the transference--counter-transference constellations
and their associated enactments in treatment of this disturbance.
PMID- 10194574
TI - GP referrals to adult psychological services: a research agenda for promoting
needs-led practice through the involvement of mental health clinicians.
AB - General practitioners' responses to psychological problems presented in the
surgery have a significant impact on the care that their patients will receive.
Importantly, their referral behaviour has a knock-on effect on the shaping of
psychological treatment services. The present paper summarizes the types of
influences that impact on GPs' referral decisions and investigates the possible
role that mental health clinicians may play in facilitating these processes. GPs'
referral decisions are shown to be affected by a large number of factors which
fall within the following domains: patients' help-seeking behaviour and their
representations of mental ill-health; the ability of GPs to detect psychological
disorders; GPs' attitudes towards psychological problems and their management;
service criteria for appropriate referral; and links with mental health services.
For each of these domains, methods by which mental health clinicians can promote
better referral practice are suggested. Recommendations are made for further
research into the efficacy and clinical utility of these methods.
PMID- 10194575
TI - Representation of goodness or badness in contacts of 5-year-old children with
mother and nursery school teacher.
AB - The present study assessed children's evaluation of their own 'goodness' or
'badness' in interactions with a caregiver. These assessments were derived from 5
year-olds' responses to interviews where (a) the adult takes the role of a child
and addresses the child as a knowledgeable fairy (with the help of two
appropriate dolls), and (b) the adult addresses the child directly. These
interviews referred to positive as well as negative contacts with two different
adult figures, mother and nursery school teacher; and two different child-rearing
settings, town and kibbutz. The sample consisted of 72 5-year-olds drawn from
both kibbutzim and towns in Israel. Results indicated that children's
representation of self-goodness or self-badness, in positive as well as negative
contacts, was more positive in the role of self than in the role of a fairy. The
difference between these representations was larger among kibbutz children than
among town peers. Statistical interactions were obtained (three-way child role by
nature of contact by place of origin) for contacts with mother, and were not
replicated in child contacts with the nursery school teacher. These findings
suggest that the regulation of feelings of goodness or badness of 5-year-old
children is facilitated and sustained by 'lived' experiences with significant
other, as compared with as if relations.
PMID- 10194576
TI - The plans in unplanned pregnancy: secondary gain and the partnership.
AB - A total of 128 North London women were interviewed using a semi-structured
interview technique. Life-events, difficulties, variables relating to the quality
of their sexual partnerships, self-esteem and the secondary gain inherent in
becoming pregnant were examined. Results indicated that women with unplanned
pregnancies were significantly more likely to have been in a situation of
potential secondary gain from a pregnancy than were women with planned
pregnancies and women who were not pregnant. Measurements of the women's
partnerships were also linked to the intentionality of pregnancy. The
implications of these results are discussed.
PMID- 10194577
TI - Doctors' narratives in Balint groups.
AB - There is a limited place today for narratives in traditional medicine. However,
the Balint group is a legitimate forum providing doctors to unconditionally
engage in discussing patients' stories within a secure and safe environment. This
paper examines the importance of doctors' narratives in Balint groups and
describes how insightful listening may help them move from a mainly biomedical
mode to a narrative one, in order to change and repair their patients' and their
own personal narratives.
PMID- 10194578
TI - Accessing the literature on outcome studies in group psychotherapy: the
sensitivity and precision of Medline and PsycINFO bibliographic database
searching.
AB - BACKGROUND: Bibliographic databases such as Medline and PsycINFO are major
sources of initial information for systematic reviews. This study investigates
the adequacy of Medline and PsycINFO in retrieving articles describing outcome
studies of group-based psychological treatments. METHOD: Ten journals publishing
a high number of group psychotherapy articles were hand searched for the
publication years 1993 and 1994. They were then searched using narrow and broad
strategies developed for each database. RESULTS: The sensitivities (number of
relevant articles identified by each search divided by the total number of known
relevant articles identified by all searches) of narrow and broad Medline
searches were 28% and 67% respectively. Precision (the number of relevant
articles identified by a search divided by the number of both relevant and
irrelevant articles identified by the search) was 91% and 35% for narrow and
broad searches respectively. The sensitivities of narrow and broad PsycINFO
searches were 8% and 47% respectively. Precision was 30% for the narrow search
and 36% for the broad search. The hand search identified 94% of all known
articles. CONCLUSIONS: PsycINFO performed more poorly than Medline. Although it
was possible to identify 67% of outcome studies using Medline, the low precision
of the necessary search strategies would make it uneconomical in practice.
Abstracts of papers not identified by either search strategy were examined for
possible reasons for this failure. For Medline this was generally due to the
terms used to identify group psychotherapy. For PsycINFO it appears that the
indexing system does not allow the easy identification of outcome studies.
PMID- 10194579
TI - Clinical Oncology Information Network: from drawing board to reality.
PMID- 10194580
TI - Breast screening: process and outcome.
PMID- 10194581
TI - Acquired immunodeficiency syndrome-related primary cerebral lymphoma.
PMID- 10194582
TI - The COIN workstation: state of the future art.
AB - This is a description of the clinical workstation now under development by the
Clinical Oncology Information Network (COIN) Project at the Clinical Oncology
Centre, North Middlesex Hospital, London, UK. It comprises: introduction;
background; technical requirements; design; what the workstation does; how the
workstation does it; future plans; glossary; and 26 figures showing screen shots
of the workstation in use. The following article sets out the guidance on the
creation of evidence-linked guidelines issued to the COIN Specialty Working
Groups charged in 1995 with producing clinical guidelines for breast, colorectal,
lung, prostate and testicular cancer and generic guidelines for the delivery of
radio- and chemotherapy on behalf of the Faculty of Clinical Oncology of The
Royal College of Radiologists and the Joint Council for Clinical Oncology. The
first of these guidelines, for lung cancer, is published elsewhere in this issue.
PMID- 10194583
TI - Guidance on the creation of evidence-linked guidelines for COIN.
AB - This guidance on the creation of evidence-linked guidelines was issued to the
COIN Specially Working Groups charged in 1995 with producing clinical guidelines
for breast, colorectral, lung, prostate and testicular cancer and generic
guidelines for the delivery of radio- and chemotherapy on behalf of the Faculty
of Clinical Oncology of The Royal College of Radiologists and the Joint Council
for Clinical Oncology. The first of these guidelines, for lung cancer, is
published elsewhere in this issue.
PMID- 10194584
TI - Computerizing the cancer centre.
AB - This article describes a PC-based computer network that caters for the clinical
information needs of a cancer centre, crossing specialty boundaries and involving
all members of the multidisciplinary team. Data are captured at all stages of
patients' progress, from diagnosis through to treatment and follow-up. Office
automation is integral to the system, which produces work-load and process audit
information as well as clinical outcomes. Data are entered prospectively at the
point of care by health care professionals, ensuring a high degree of clinical
confidence. It incorporates internationally recognized datasets and its modular
structure facilitates implementation and development.
PMID- 10194585
TI - Outcome of radiotherapy after breast conserving surgery in screen detected breast
cancers.
AB - The treatment outcomes were reviewed for all the patients at this institute who
underwent breast irradiation after breast conserving surgery in 1991. Of a total
of 643 patients treated, 194 (30%) had presented with tumours detected by
screening mammography. The breast was irradiated with a tangential pair of
fields, giving a dose of 40 Gy in 15 fractions over 3 weeks in 97% of these
patients. A boost was not used. With a median follow-up of 4.7 years, there was
better cancer related survival in patients with screen detected cancers compared
with those that were non-screen detected (94% versus 84% at 5 years; P = 0.002).
The breast recurrence rate at 5 years was 1% for screen detected cancers compared
with 6% for those that were non-screen detected (P = 0.01). Factors additional to
screen detected status that were found to be significant for cancer survival were
pathological stage (P = 0.03) and histological grade (P = 0.01). In a Cox
multivariate analysis, only two factors were significant for breast recurrence:
screen detected status (P = 0.023) and histological grade (P = 0.016). This study
suggests that breast irradiation with 40 Gy given over 3 weeks after breast
conserving surgery for screen detected breast cancer gives a high level of local
control out to 5 years.
PMID- 10194586
TI - Prevention of vaginal stenosis in patients following vaginal brachytherapy.
AB - The assessment of patients following intracavitary irradiation administered as
part of the treatment of gynaecological malignancy reveals vaginal stenosis in
the majority. Vaginal dilators are available for daily insertion in an attempt to
prevent the formation of adhesions. However, the design of the dilator neglects
the fact that the vagina is the most distensible in the upper third and hence
many patients develop stenosis of the upper vagina. Many clinicians have
abandoned the use of dilators and instead advise patients to have sexual
intercourse to prevent the problem. In 1994, we designed a new vaginal stent,
which was given to all patients who had received intracavitary irradiation with
full instructions about its use. This stent was designed to suit better the true
anatomy of the vagina and hence, with correct use, should prevent vaginal
stenosis. A retrospective study was undertaken to look at the incidence of
vaginal stenosis and this was compared with the incidence in patients using the
new stent. The study revealed that 57% of the patients who were advised to have
sexual intercourse had stenosis, whereas 11% of the patients using the stent had
evidence of stenosis, which, however, was related to their incorrect use of the
stent. In those who used the stent correctly there was no evidence of vaginal
stenosis. Details of the design of the stent and the problems relating to those
who used the stent incorrectly are presented. The findings of this study strongly
support the continued use of this vaginal stent in patients who have undergone
intracavitary irradiation as a means of preventing this common complication.
PMID- 10194587
TI - Primary non-Hodgkins lymphoma of muscle.
AB - A retrospective analysis was made of all patients with primary muscle non
Hodgkin's lymphomas registered with the Scotland and Newcastle Lymphoma Group
over a 15-year period. Only eight patients were identified. The median age was 69
years (range 27-93). Five patients were male and six lymphomas were of high grade
histology. The glutei and upper arm muscles were the main sites of origin, with
the additional involvement of adjacent bone in four patients; only three had
lymph node involvement at presentation. Most patients (6/8) received both
chemotherapy and radiotherapy. The median survival was 33 months. The conclusion
is that this is a small group of patients whose outlook is not as poor as has
been suggested in previous reports.
PMID- 10194588
TI - Breast cancer in Scotland: changes in treatment and work-load. Scottish Breast
Cancer Focus Group and the Scottish Cancer Therapy Network.
AB - Throughout Scotland, the patterns of care of patients with breast cancer were
examined for the years 1987 and 1993. Substantial changes in oncological work
load were shown in the intervening period. The number of patients referred to an
oncologist (clinical or medical) increased by 52% (from 1076 to 1634), the number
of patients receiving postoperative radiotherapy to the breast or chest wall
increased by 72% (from 724 to 1248) and the number of patients receiving adjuvant
chemotherapy increased by 215% (from 123 to 388). The number of consultant
oncologists increased by only 16% (from 32 to 37). If patients are to be treated
to the standards expected, then increases in work-load must be matched by
appropriate increases in staff.
PMID- 10194589
TI - Fifty years of the National Health Service 1948-1998: a personal history of
progress in the treatment of cancer.
PMID- 10194590
TI - Ductal carcinoma in situ recurrent on the chest wall after mastectomy.
AB - Two patients with local recurrence on the chest wall subsequent to mastectomy for
ductal carcinoma in situ (DCIS) are presented. One recurrence was invasive
carcinoma and the second was DCIS. Excision and chest wall irradiation, together
with chemotherapy in the first patient, have provided subsequent disease-free
survivals of 6 and 12 years respectively. Although mastectomy for DCIS is almost
always curative, the possibility of local recurrence requires careful
surveillance.
PMID- 10194591
TI - Testicular seminoma in a patient with ataxia-telangiectasia.
AB - The case history of a 27-year-old man with ataxia-telangiectasia (AT) and
testicular seminoma is reported. This is the first documented description of such
a malignancy in AT, a syndrome associated with a markedly increased risk of
malignant disease. Furthermore, alpha-foetoprotein levels have limitations as a
tumour marker in this situation because serum levels may be elevated as a
biochemical manifestation of AT.
PMID- 10194592
TI - Cervical spine involvement in metastatic colorectal carcinomas: should we think
about an alternative route of metastasis other than Batson's plexus?
PMID- 10194593
TI - The use of raltitrexed (tomudex) in a patient with 5-fluorouracil induced
myocardial ischaemia.
PMID- 10194594
TI - Methoxybutropate microencapsulation by gelatin-acacia complex coacervation.
AB - Microcapsules of methoxybutropate solid particles or of an oily saturated
solution of the same drug were prepared by complex coacervation between gelatin
and acacia and dried with three different methods: isopropanol addition, spray
drying, and freeze-drying. Successively, microparticles were analyzed by infrared
thermobalance, ultraviolet (UV) spectroscopy, optical and scanning electron
microscopy, and sieves to find out parameters such as yield, moisture content,
encapsulation percentage, morphology of solid particles, and particle size.
Results highlighted that the most appropriate drying method for industrial
purposes was spray-drying, particularly for oil-containing microcapsule
formulations.
PMID- 10194595
TI - Solubility and stability of lorazepam in bile salt/soya phosphatidylcholine-mixed
micelles.
AB - In the present study, the solubility and stability of the drug lorazepam, which
was solubilized in bile salt/soya phosphatidylcholine-mixed micelles (BS/SPC
MMs), were investigated. The solubility of lorazepam could be enhanced
substantially in different bile salts and also in sugar ether, whereas the
solubility in Pluronic F68 (Pl.F68) was of lower order. Moreover, the addition of
SPC to different BS solutions greatly enhanced their solubilizing capacities
toward lorazepam; this could be correlated with the ability of the formed MM to
reduce the surface tension. The stability study showed that lorazepam degradation
followed apparent first-order degradation kinetics in phosphate buffer, as well
as in the BS/SPC-MM, with highly enhanced stability in the latter system. The
stabilizing effect of BS/SPC-MM was higher in the case of trihydroxy BS than for
dihydroxy BS. From an Arrhenius plot with degradation constants in a temperature
range from 30 degrees C to 60 degrees C, a shelf stability of about 10 months
could be calculated for BS/SPC-MM at 5 degrees C. The solubility studies in
BS/SPC-MM showed a recrystallization and a polymorphic transition from
modification II to I.
PMID- 10194596
TI - Interaction of two diclofenac acid salts with copolymers of ammoniomethacrylate:
effect of additives and release profiles.
AB - The copolymer of ammoniomethacrylate Eudragit RL (ERL) interacted with diclofenac
acid salts (sodium and diethylamine salts) in aqueous solutions, forming a
complex. Sorption experiments were done in aqueous solutions of either sodium
lauryl sulfate (SLS), Tween 20, or Tween 80. The SLS competed strongly with the
drug, even at low concentrations, and reduced significantly the amount of drug
sorbed by ERL. Tweens at high concentrations exhibited two phase profiles: the
sorption phase, which was short and during which drug concentration dropped
sharply, and the release phase, during which the drug was released slowly over 24
hr and which was accompanied by dispersion of ERL particles into the colloidal
dispersion. The interaction was dependent on temperature, ionic strength, and
nature of the additives. The extent of interaction in water and phosphate buffer
solutions was in the following order: water > pH 6 > pH 7-8. In-vitro dissolution
studies of the dried complex were done over 24 hr. In water, the drug remained
bound to the polymer. In aqueous surfactant solutions (SLS, Tween 20, and Tween
80) and phosphate buffer at pH 6.8, a linear relationship between drug
concentration and the square root of time was obtained, indicating a matrix
diffusion-controlled mechanism. However, 100% release was not reached, and
resorption was observed in the phosphate buffer solution.
PMID- 10194597
TI - In vivo performance of wax matrix granules prepared by a twin-screw compounding
extruder.
AB - The in vivo performance of wax matrix granules (WMGs) prepared by a twin-screw
compounding extruder was evaluated in fasted beagle dogs. In vitro dissolution
behavior of the model drug, diclofenac sodium (DS), from WMGs was strongly
influenced by pH in a dissolution medium due to its solubility (DS is soluble in
pH 6.8 and insoluble in pH 1.2 and 4.0) and was independent of paddle rotation
rate (50, 100, and 200 rpm) of the dissolution apparatus. Pharmacokinetics
parameters such as mean residence time (MRT) showed a sustained action of WMGs in
beagle dogs; however, the transit time of WMGs in the small intestine is found to
control total drug absorption. Furthermore, the values of the area under the
curve (AUC) of the plasma concentration-time curve and the maximum concentration
Cmax significantly decreased with decreases in hydroxypropylcellulose (HPC)
content in WMGs. Good correlation between one in vitro dissolution parameter
(mean dissolution time, MDT) and two in vivo parameters (AUC12 and MRT) suggested
that it would be possible to design WMGs with a desired in vivo performance by
controlling HPC content.
PMID- 10194598
TI - Swelling and ketoprofen release characteristics of thermo- and pH-responsive
copolymer gels.
AB - Swelling-controlled drug delivery copolymer gels were newly synthesized by
introducing thermo- and pH-responsive methacryloyl-glycine (MA-Gly) or pH
responsive methacrylic acid (MA-Ac) for comparison with thermoresponsive acryloyl
L-proline ethyl ester (A-ProOEt). A homopolymer gel of A-ProOEt was kept at
degrees of swelling that were less than 0.5 at a pH from 2.5 to 7.5 at 37 degrees
C. The thresholds of swelling for copolymer gels consisting of A-ProOEt/MA-Gly
and A-ProOEt/MA-Ac with a composition of 40/60 mol% were found to be pH 3.0 and
pH 5.5, respectively, in buffer solutions at 37 degrees C. The diffusion
characteristics of 2-(3-benzoylphenyl)propionic acid (ketoprofen) from such
copolymer gels was evaluated in buffer solutions at pH's more than 5.5, and it
was found that A-ProOEt/MA-Gly gel possesses a case II transport mechanism that
is completely linear time dependent in both the amount diffused and the
penetrating swelling front position. On the other hand, A-ProOEt/MA-Ac gel
exhibited a non-Fickian (or anomalous) diffusion behavior under the same
conditions.
PMID- 10194599
TI - Prevention of small black spots on sugar-coated tablets containing aluminum
acetylsalicylic acid.
AB - Sugar-coated tablets containing aluminum acetylsalicylate gradually developed
black spots on their surface. A factorial experiment was performed based on an
L32 orthogonal array table in an attempt to halt this phenomenon. The factor
responsible proved to be talc used to formulate the smooth coating layer over the
subcoating layer containing aluminum acetylsalicylate. When HCl-treated talc was
used as a filler for the smoothing layer, the black spots were markedly
decreased. The spotting mechanism was considered to be due to hydrolysis of
aluminum acetylsalicylate in the subcoating layer to salicylic acid and acetic
acid, which sublimated into the pores of the smoothing layer. Then, ferrous ion
substituted from magnesium ion in the talc molecule center was extracted by
salicylic acid, acetic acid, and moisture. Finally, the ferrous ion was oxidized
to ferric ion, and this produced an Fe3+ chelate compound together with salicylic
acid.
PMID- 10194600
TI - Effects of thermal neutron irradiation on some potential excipients for colonic
delivery systems.
AB - Different excipients, which are currently being studied for colon delivery
systems, were examined with respect to their stability toward neutron irradiation
as a potential method of radiolabeling the formulations for gamma-scintigraphic
studies. Three different pectin and four different hydroxypropyl methylcellulose
(HPMC) types, in addition to two types of polymethacrylate films, were exposed to
1, 2, and 3 min of thermal neutron irradiation in a flux of 1.1 x 10(13) n cm-2 s
1. The physicochemical characteristics of pectins and HPMCs and the mechanical
properties of the polymethacrylate films were examined after the radioactivity of
the samples had declined to background levels. Methods included ultraviolet (UV)
and Fourier transform infrared (FTIR) spectroscopy, pH measurements, loss on
drying, thermogravimetric analysis (TGA), viscosimetry, gas chromatographic (GC)
analysis of pectin monosaccharides, and tensile strength testing of the films.
The results suggest that pectins and HPMCs undergo degradation, as expressed by a
significant reduction in the dynamic and intrinsic viscosities of the samples.
Generally, HPMCs were more sensitive than pectins to neutron irradiation.
However, calcium pectinate proved to be the most sensitive among all the
investigated polymers. Both polymethacrylate films (Eudragit L and S) resisted
loss of mechanical properties following 1 and 2 min of neutron irradiation,
whereas irradiation for 3 min implied significant changes in the appearance and
the mechanical properties of Eudragit L films. As a conclusion, neutron
irradiation results in dose-dependent degradation of the investigated
polysaccharides and polymethacrylates. The consequences on the in vitro behavior
of a formulation containing such polymers are discussed.
PMID- 10194601
TI - Cyclodextrin inclusion complexes of miconazole and econazole--isolation, toxicity
on human cells, and confirmation of a new interpretation of the drug
supersaturation phenomenon.
AB - Parameters that influence the precipitation of the beta-cyclodextrin (beta-CD)
inclusion complexes of the antimycotics miconazole and econazole were
investigated. The mechanistic reason for the superior antimycotic activity of the
miconazole inclusion complex was studied. The toxicity of the complex was
estimated. The temperature, the buffer strength, and the effect of the addition
of hydrotropic agents on the CD solubility diagrams for the antimycotics were
estimated. The miconazole and the CD dissolution rate for the complex was
measured. The hemolytic activity of the miconazole inclusion complex, the
physical mixture, miconazole, and the nitrate salt were compared. The toxicity on
TR146 oral cell layers was measured. Lowering the temperature meant that both
complexes precipitated at lower CD concentrations. Addition of hydrotropic agents
and variation of the buffer strength affected the solubility diagrams. The
dissolution medium was supersaturated with miconazole. The supersaturation was
not disclosed by the traditional method to analyze for drug supersaturation. The
miconazole complex was more toxic to erythrocytes than the physical mixture. On
the other hand, the toxic effects of the two products on the TR146 cell layers
were similar. Lowering the temperature eased the isolation of genuine CD
inclusion complexes of miconazole and econazole. The miconazole supersaturation
is likely to be the reason for the superior antimycotic activity of the complex.
The complex and the physical mixture had about the same toxicity on TR146 cell
layers.
PMID- 10194602
TI - Encapsulation of hydrophilic and lipophilic drugs in PLGA nanoparticles by the
nanoprecipitation method.
AB - The purpose of this study was to assess the relative advantages and drawbacks of
the nanoprecipitation-solvent displacement method for a range of drugs with
respect to the particle size and drug encapsulation in polylactic-co-glycolic
acid (PLGA) nanoparticles. The particle size analysis indicated a unimodal
particle size distribution in all systems, with a mean diameter of 160-170 nm,
except for insulin nanoparticles, which showed a smaller particle size. The
results of the encapsulation efficiency analysis demonstrated that more
lipophilic drugs, such as cyclosporin and indomethacin, do not suffer from the
problems of drug leakage to the external medium, resulting in improved drug
content in the nanoparticles. In spite of the fact that valproic acid is a liquid
that is very sparingly soluble in water, very low encapsulation efficiency was
obtained. Ketoprofen, a drug sparingly soluble in water, demonstrated
intermediate values of encapsulation that were well correlated with its
intermediate lipophilicity. More hydrophilic drugs, such as vancomycin and
phenobarbital, were poorly encapsulated in PLGA nanoparticles. Insulin was
preferentially surface bound on the PLGA nanoparticles. However, a strong
hypoglycemic effect of the insulin was observed after administration of the
suspension of PLGA nanoparticles with surface-bound insulin to the ileum loop of
male Wistar rats.
PMID- 10194603
TI - Development of terbutaline sulfate sustained-release coated pellets.
AB - Sustained-release coated pellets containing terbutaline sulfate (TS) 1.8% w/w
were prepared. The suitable core formulation that gave round-shape TS pellets was
preformulated and was composed of microcrystalline cellulose:lactose
38.61%:57.92%, hydroxypropyl cellulose (HPC-M) 1.67%, and water 40%,
respectively. The core pellets containing active drug were coated with various
amounts of ethylcellulose (EC) and a combination of EC/HPC-M polymers. The
effects of fluidized bed polymeric film coats on drug release were studied in
vitro. The dissolution characteristics were also investigated. The release of the
active drug decreased as the amount of EC increased. This may be due to water
insoluble EC film, leading to decreased permeability in water. In the case of the
combination of EC/HPC-M, the release of the active drug increased as the amount
of HPC-M in the coating solution increased. Since HPC-M is a water-soluble
polymer, it may be suggested that formation of pores were increased in the
coating layer. Among five coating formulas in this study, formulation 1 (F1) (at
1.1% EC concentration) shows a similar dissolution profile to Bricanyl Durules;
however, lag time for the release occurred. In conclusion, the formulation that
gave an insignificant release profile (p < .01) when compared with commercial
product was the capsule containing F1 (at 1.1% EC concentration) mixed with
uncoated pellets at a ratio of 7:1, and the release was found to be reproducible.
PMID- 10194604
TI - Formulation and release characteristics of hydroxypropyl methylcellulose matrix
tablet containing melatonin.
AB - A hydroxypropyl methylcellulose (HPMC) matrix tablet containing melatonin (MT)
was formulated as a function of HPMC viscosity, drug loading, type and amount of
disintegrant, lubricant and glidant, and aqueous polymeric coating level and was
compared with two commercial products. The release characteristics of the HPMC
matrix tablet were investigated in the gastric fluid for 2 hr followed by study
in intestinal fluid. The surface morphology of an uncoated HPMC matrix tablet
using scanning electron microscopy (SEM) was crude, showing aggregated particles
and rough crystals or pores, but it became smoother as the coating levels
increased. As the HPMC polymer viscosity increased, the release rate had a
tendency to decrease. As the drug loadings increased, the release rate slightly
decreased. When Polyplasdone XL, Primojel, and Ac-Di-Sol, except Avicel, were
incorporated in the HPMC matrix tablet, the release rate was markedly increased.
There was no significant difference in release profiles when a mixture of
lubricants and glidants (magnesium stearate, talc, and Cab-O-Sil), except for
magnesium stearate alone, was incorporated into low and high viscosity grade HPMC
matrix tablets. As the coating level increased, the release rate gradually
decreased, giving an increased lag time. The sustained-release HPMC matrix tablet
with optimizing formulations may provide an alternative for oral controlled
delivery of MT and be helpful in the future treatment of circadian rhythmic
disorders.
PMID- 10194606
TI - Effect of polysorbates on atenolol release from film-coated tablets.
AB - The effects of different concentrations of various polysorbates on the release
rate of atenolol from film-coated tablets were evaluated. The release profile of
atenolol showed that increasing the concentration of polysorbate resulted in an
increase in the release rate of atenolol. The type of polysorbate had less effect
on the release rate of atenolol. This study revealed that the release kinetic of
atenolol from these film-coated tablets was a function of polysorbate
concentration. Correlation coefficients of kinetic models could not solely
determine the suitability of the models; the sum of the least square of
differences also should be calculated when different kinetic models have similar
correlation coefficients.
PMID- 10194605
TI - The compression of spheres coated with an aqueous ethylcellulose dispersion.
AB - Tablets were compressed from commercial samples of Sugar Spheres NF, Sucrose NF,
Corn Starch NF, as well as ground spheres and a physical mixture of ground
sucrose plus cornstarch. Additional tablets were compressed from spheres that had
been coated with a water-soluble cellulosic polymer solution followed by an
aqueous ethylcellulose dispersion. Tableting parameters measured "in-die"
included work of compression, peak offset time, tablet density, and Young's
modulus. Following ejection, tensile strength was determined under diametrical
loading. Dissolution of a marker contained in the water-soluble layer was
determined for both compressed and uncompressed spheres. Porosities at peak
pressure and peak offset times or tensile strength as functions of peak pressure
did not differ between tablets compressed from pristine spheres or from ground
spheres. Tablets compressed from spheres had higher values for porosity, tensile
strength, and peak offset time than those compressed from sucrose or the sucrose:
starch mixture. Values for work of compression were higher for tablets compressed
from pristine spheres or from starch. This was attributed to the work required
for particle deformation and for breaking of the spheres. The greatest elastic
recovery during decompression was observed for tablets compressed from pristine
spheres or starch. More brittle behavior was observed for tablets compressed from
sucrose or the sucrose: starch mixture. Tablets compressed from ground spheres
were more brittle than those compressed from the pristine spheres, indicating an
effect due to grinding. Most mechanical properties of tablets compressed from the
coated spheres were comparable to those of tablets compressed from uncoated
spheres. An exception was diametric strain for tablets compressed from spheres
coated with the aqueous ethylcellulose dispersion. These values increased since
the plasticized ethylcellulose allowed greater distortion of the tablet before
failure occurred. The dye marker was released more rapidly from tablets
compressed from spheres coated with the aqueous ethylcellulose dispersion than
from comparable uncompressed spheres. At both the 5% and 10% coating levels,
spheres coated with the aqueous ethylcellulose dispersion fused into
nondisintegrating matrices during compression. Little difference in release rates
was seen between the two tablets.
PMID- 10194607
TI - The in vivo effect of liposomes on hematopoiesis.
AB - The influence of liposome structure on hematopoiesis in vivo was assessed in
relation to the different contents and origins of phospholipids that make up
their membrane structures. Changes within different hematopoietic cells and serum
tumor necrosis factor alpha (TNF-alpha) levels were estimated up to 14 days
following intravenous administration of liposomes made of either pure egg yolk
phosphatidylcholine (LEY) or a soybean phospholipid preparation (LSB) into normal
CBA mice. In peripheral blood, only transient changes within white blood cells
were observed. In bone marrow, a persistent decline in the number of mature
granulocytes, monocytes, and lymphocytes was found. The changes within femoral
granulocytic proliferative compartments in various stages of differentiation and
a maturation compartment pointed out that, parallel with the depletion of the
granulocyte-storage pool, stimulation of de novo production of granulocytic cells
occurred. Although both types of tested liposomes induced similar cellular
changes, only liposomes made of pure egg yolk phosphatidylcholine induced a
transient increase in serum TNF-alpha levels.
PMID- 10194608
TI - Synthesis and properties of disodium tetraethyleneglycol-bis-(alpha
carboxybenzylpenicillin).
AB - Disodium tetraethyleneglycol-bis-(alpha-carboxybenzylpenicillin) (TEG
carbenicillin), a tetraethyleneglycol (TEG) diester of carbenicillin, was
synthesized to develop a carbenicillin prodrug with enhanced acid stability for
oral administration. Antimicrobial activities of TEG-carbenicillin tested against
gram-negative Escherichia coli (TG-1) and gram-positive Staphylococcus aureus
(ATCC-12228) and Bacillus subtilis (NA-1) were comparable to that of
carbenicillin. Stability of the beta-lactam ring of TEG-carbenicillin was
determined by iodometry at pH 6.8, pH 4.5, and pH 2.0 at varied time intervals
and was compared to that of carbenicillin. In 26 hr, both of the compounds were
stable at pH 6.8. At pH 4.5, about 41% of the carbenicillin was decomposed, while
TEG-carbenicillin was not appreciably decomposed. At pH 2.0, carbenicillin was
decomposed about 61% after 6 hr, while TEG-carbenicillin was decomposed about 21%
during the same period.
PMID- 10194609
TI - Comparative pharmacodynamic-pharmacokinetic correlation of oral sustained-release
theophylline formulation in adult asthmatics.
AB - A sustained-release formulation of theophylline with an innovative release
mechanism was evaluated in adult asthmatics. The pharmacodynamics and
pharmacokinetic behavior of this formulation was compared with a market
formulation (Theobid). The formulations, each containing 200 mg of anhydrous
theophylline, were evaluated in six male subjects, 40-55 years of age, 151-169 cm
in height, 41-60 kg in weight, who were nonsmokers with moderate chronic
obstructive pulmonary disease (COPD); the study was a randomized, single-dose,
open, complete crossover study with an interval of 1 week. Written consent was
obtained from the patients prior to the trial. Plasma samples were obtained at 0,
1, 2, 4, 6, 8, 10, and 12 hr postadministration. Pulmonary functions were
simultaneously recorded using an Erich Jaeger spirometer. Plasma theophylline
assays were performed using high-performance thin-layer chromatography (HPTLC).
Individual bioavailability parameters were obtained using the S-Inv computer
program. Pharmacodynamic-pharmacokinetic correlation was studied using the Excel
95 version 7.0 Regression Statistics program. The test formulation (innovator)
was found to be comparable with the marketed product with respect to tmax, t1/2
and Kel (p < .05). A significant difference in the means of Cmax and AUC0-12
between the innovator and the market formulation indicated a superior extent of
absorption from the innovator formulation. A good pharmacodynamic-pharmacokinetic
correlation was observed when plasma theophylline concentration was compared with
forced expiratory volume.
PMID- 10194610
TI - Dissolution kinetics evaluation of controlled-release tablets containing
propranolol hydrochloride.
AB - In the present research, controlled-release propranolol hydrochloride tablets
were prepared for twice-daily administration, allowing more uniform plasmatic
levels of the drug. Pharmaceutical formulations were prepared with hydrophobic
Eudragit RSPO. The physical properties of the tablets were determined.
Dissolution tests were performed in capsules containing the raw material using
the following dissolution media: (A) distilled water, (B) simulated gastric juice
without enzymes, and (C) simulated enteric juice without enzymes. A dissolution
test was also performed for simulated samples (tablets) using distilled water as
the dissolution medium.
PMID- 10194611
TI - Inclusion complexation of nimesulide with beta-cyclodextrins.
AB - Nimesulide (NM), a nonsteroidal anti-inflammatory drug (NSAID) has poor aqueous
solubility. The present study describes the complexation of NM with beta
cyclodextrin (beta-CD) and its derivative hydroxypropyl beta-cyclodextrin (HP
beta-CD). The complexation was studied by phase solubility method, Fourier
transformed infrared (FTIR) spectroscopy, differential scanning calorimetry
(DSC), and X-ray diffractometry (XRD). The complexes were prepared by a freeze
drying technique. The in vitro dissolution rate of drug-HP beta-CD complex was
faster compared to the drug-beta-CD complex and drug alone.
PMID- 10194612
TI - Nonliposomal approach--a study of preparation of egg albumin nanospheres
containing amphotericin-B.
AB - The stability of liposomes after introduction into the body is presently being
discussed and needs thorough understanding. Hence, as a nonliposomal approach,
egg albumin nanospheres were prepared by the pH-coacervation method, and a
preliminary study was carried out of the influence of process variables on the
size and shape of nanospheres by changing the pH of the albumin solution,
concentration of albumin solution, and volume of cross-linking agent. The batch
prepared with an albumin medium of pH 9, 2% concentration, and 100 microliters of
4% glutaraldehyde-ethanol solution was found to have a spherical uniform shape
with an average size of 497.6 nm. The ideal batch was loaded with the systemic
antifungal drug amphotericin-B. Drug-loaded nanospheres were evaluated to study
their in vitro release. They were found to exhibit a biphasic pattern with a
cumulative percentage release of 97.7%.
PMID- 10194613
TI - Comments on drugs difficult to compound and the quality of chemicals to be used
in compounding.
AB - These comments are minor modifications to the material submitted by the author to
the docket for the FDA Pharmacy Compounding Committee that met on October 15 and
16, 1998.
PMID- 10194614
TI - Some observations on current and possible future developments in bioequivalency
testing.
AB - Present trends in the evolution of the design and interpretations of
bioequivalency studies are reviewed. It is suggested that, although such tests
are now being increasingly regarded as clinical mirrors rather than simply
quality control tests for final product testing, there is still the possibility
of simplifying such procedures. However, care must be exercised to ensure that
changes in bioequivalency tests are introduced only after careful public
discussions, which should involve both regulators and pharmaceutical scientists
from academia and industry. Further, it is important that bioequivalency
standards shall be internally consistent and applied in a politically neutral
manner.
PMID- 10194615
TI - Ethical issues in the design and conduct of randomised controlled trials.
PMID- 10194616
TI - Effect of partition coefficient, permeability surface product, and radioisotope
on the signal-to-noise ratio in PET functional brain mapping: a computer
simulation.
AB - In this work we use a computer simulation to estimate the magnitude of
improvement in the signal-to-noise ratio of PET functional brain mapping studies
as a function of partition coefficient and permeability surface product for O-14,
F-17, and O-15 labeled flow tracers. A model for signal-to-noise ratio is derived
from the Kety model for inert diffusible blood flow tracers. The results of the
simulation suggest that moderate increases in partition coefficient and
permeability surface product compared with water would lead to an increase in
signal-to-noise ratio of a factor of about 3.
PMID- 10194617
TI - Backus and Gilbert method for vector fields.
AB - This report describes the theory of Backus and Gilbert with special emphasis for
the case of vector fields as required for the solution of the electromagnetic
inverse problem. A description of the method is presented with the detailed
mathematical derivation of the coefficients that determine the solution for the
retrieval of vector fields. Such derivation, to our knowledge, has never been
reported in the literature. We also identify some crucial points that can (and
had) lead to misuse of this solution and describe some disadvantages of this
theory for the case of vector fields suggesting some alternatives to deal with
them.
PMID- 10194618
TI - Analysis of brain activation patterns using a 3-D scale-space primal sketch.
AB - A fundamental problem in brain imaging concerns how to define functional areas
consisting of neurons that are activated together as populations. We propose that
this issue can be ideally addressed by a computer vision tool referred to as the
scale-space primal sketch. This concept has the attractive properties that it
allows for automatic and simultaneous extraction of the spatial extent and the
significance of regions with locally high activity. In addition, a hierarchical
nested tree structure of activated regions and subregions is obtained. The
subject in this article is to show how the scale-space primal sketch can be used
for automatic determination of the spatial extent and the significance of rCBF
changes. Experiments show the result of applying this approach to functional PET
data, including a preliminary comparison with two more traditional clustering
techniques. Compared to previous approaches, the method overcomes the limitations
of performing the analysis at a single scale or assuming specific models of the
data.
PMID- 10194619
TI - Bayesian inference applied to the electromagnetic inverse problem.
AB - We present a new approach to the electromagnetic inverse problem that explicitly
addresses the ambiguity associated with its ill-posed character. Rather than
calculating a single "best" solution according to some criterion, our approach
produces a large number of likely solutions that both fit the data and any prior
information that is used. Whereas the range of the different likely results is
representative of the ambiguity in the inverse problem even with prior
information present, features that are common across a large number of the
different solutions can be identified and are associated with a high degree of
probability. This approach is implemented and quantified within the formalism of
Bayesian inference, which combines prior information with that of measurement in
a common framework using a single measure. To demonstrate this approach, a
general neural activation model is constructed that includes a variable number of
extended regions of activation and can incorporate a great deal of prior
information on neural current such as information on location, orientation,
strength, and spatial smoothness. Taken together, this activation model and the
Bayesian inferential approach yield estimates of the probability distributions
for the number, location, and extent of active regions. Both simulated MEG data
and data from a visual evoked response experiment are used to demonstrate the
capabilities of this approach.
PMID- 10194620
TI - "Sparse" temporal sampling in auditory fMRI.
AB - The use of functional magnetic resonance imaging (fMRI) to explore central
auditory function may be compromised by the intense bursts of stray acoustic
noise produced by the scanner whenever the magnetic resonance signal is read out.
We present results evaluating the use of one method to reduce the effect of the
scanner noise: "sparse" temporal sampling. Using this technique, single volumes
of brain images are acquired at the end of stimulus and baseline conditions. To
optimize detection of the activation, images are taken near to the maxima and
minima of the hemodynamic response during the experimental cycle. Thus, the
effective auditory stimulus for the activation is not masked by the scanner
noise. In experiment 1, the course of the hemodynamic response to auditory
stimulation was mapped during continuous task performance. The mean peak of the
response was at 10.5 sec after stimulus onset, with little further change until
stimulus offset. In experiment 2, sparse imaging was used to acquire activation
images. Despite the fewer samples with sparse imaging, this method successfully
delimited broadly the same regions of activation as conventional continuous
imaging. However, the mean percentage MR signal change within the region of
interest was greater using sparse imaging. Auditory experiments that use
continuous imaging methods may measure activation that is a result of an
interaction between the stimulus and task factors (e.g., attentive effort)
induced by the intense background noise. We suggest that sparse imaging is
advantageous in auditory experiments as it ensures that the obtained activation
depends on the stimulus alone.
PMID- 10194621
TI - Statistical methods for the analysis of cancer survival data.
PMID- 10194622
TI - World standard cancer patient populations: a resource for comparative analysis of
survival data.
PMID- 10194623
TI - Interpretation of population-based cancer survival data.
PMID- 10194624
TI - Database on cancer survival from developing countries.
PMID- 10194625
TI - Population-based cancer survival in Qidong, People's Republic of China.
PMID- 10194626
TI - Cancer survival in Shanghai, People's Republic of China.
PMID- 10194627
TI - Cancer survival in Cuba.
PMID- 10194628
TI - Population-based survival from breast and cervical cancer and lymphoreticular
malignancies in Bangalore, India.
PMID- 10194629
TI - Survival from cervical cancer in Barshi registry, rural India.
PMID- 10194630
TI - Survival from breast and cervical cancer in Mumbai (Bombay), India.
PMID- 10194631
TI - Cancer survival in Chennai (Madras), India.
PMID- 10194632
TI - Cancer survival in Rizal, Philippines.
PMID- 10194633
TI - Cancer survival in Chiang Mai, Thailand.
PMID- 10194634
TI - Cancer survival in Khon Kaen, Thailand.
PMID- 10194635
TI - An overview of cancer survival in developing countries.
PMID- 10194636
TI - To store or mature spermatozoa? The primary role of the epididymis.
AB - The function of the epididymis is considered in the context that it is necessary
to transport spermatozoa for internal fertilization, but is also an adaptation
involved in the competition between males to achieve paternity. Post-testicular
sperm maturation and storage occur in lower vertebrates, such as the
chondrichthyes, in which sperm storage is essential due to the slow rate of
spermatogenesis. These roles persist in higher vertebrates, including mammals.
However, they are less important in certain birds, in which the rate of sperm
production by the testes is sufficient to supply enough spermatozoa to cope with
the demands of a competitive mating system. There is no evidence for mammals,
other than humans, that spermatozoa can achieve the capacity to fertilize an ovum
without passing through some of the proximal epididymis. Storage of spermatozoa
in the epididymis is probably not essential for a male to achieve conception in a
protected mating system, but is very important in a competitive mating system.
There is some variation between species in the magnitude of the epididymal
storage region. This is related to the descent of the epididymides (and testes)
into a scrotal sac in some species and/or the demands of the mating system in
other species. The claims that humans are not dependent on post-testicular sperm
maturation and storage need to be qualified, as they are based on studies of
abnormal tracts and tests of fertility which are not rigorous. Nevertheless, the
claims are of considerable clinical significance and may indicate that humans are
less dependent on post-testicular sperm maturation and storage than other
mammals. This may be an adaptation of the testes and epididymides to the scrotal
conditions of modern man or a response to changing environmental factors.
PMID- 10194637
TI - Effects of male accessory sex glands on sperm decondensation and oocyte
activation during in vivo fertilization in golden hamsters.
AB - Removal of paternal male accessory sex glands (ASG) could cause a delay in DNA
synthesis in hamster zygotes fertilized in vivo. In view of the fact that this
process is closely related to pronuclear development which, in part, depends on
sperm nuclear decondensation and oocyte activation during fertilization, we
carried out a series of experiments were undertaken to determine whether ASG also
has an effect on these early events. (1) Oocytes were collected from females
mated with SH (sham-operated control), AGX (bilateral excision of ampullary
glands), VPX (bilateral excision of ventral prostates) or TX (excision of all
ASG) males (n = 8 per group) at 4, 5 and 6 h post coitus. (2) Epididymal
spermatozoa were incubated with total ventral prostate (VP) secretion to study
its effect on dithiothreitol-induced sperm decondensation. (3) Histone H1 kinase
activity in oocytes collected as described in (1) was determined. (4) Exocytosed
cortical granules on oocytes were labelled with FITC-LCA and quantified by a
Metamorph Imaging System. Results showed that sperm decondensation and resumption
of meiosis in oocytes in VPX and TX groups were significantly slower compared
with SH. VP secretion augmented sperm decondensation in vitro. At 4 h post
coitus, the relative activity of histone H1 kinase in the TX and VPX groups was
significantly higher than that in the SH group (p < 0.01). Cortical granule
exocytosis in the AGX group was consistently weaker at all time points studied
and was significantly lower than that of the control at 4 h post coitus (p <
0.05), while the percentage of polyspermic fertilization in the AGX group was
significantly higher compared with that in the SH group (p < 0.05). Taken
together, these results show that the lack of exposure of spermatozoa to
secretions of the ASG does not jeopardize their ability to penetrate ova,
although other aspects of their function in the early stages of gamete
interaction and subsequent initiation of embryonic development are affected.
PMID- 10194638
TI - Replicate and technician variation associated with computer aided bull sperm head
morphometry analysis (ASMA).
AB - Associations of abnormal spermatozoa with bull fertility have yielded varying
results. Manual methods of analysis are subjective and highly variable within and
between technicians, which may account for these differences. Computer-aided
sperm head morphometry appears to be a precise method of assessing sperm head
dimensions; however, the effects of replication and technician on sperm head
morphometry have not been assessed. The objective of this study was to determine
the inter- and intra-analysis and technician variation associated with computer
aided bull sperm head morphometry analysis. Semen from 10 bulls was diluted to
200 x 10(6) sperm/mL, and slide smears were prepared and stained using
haematoxylin and rose bengal. Each of two technicians analysed 250 images from
each slide, 3 times, using computer-aided sperm head morphometry analysis. The
morphometric dimensions of area, perimeter, length, width and width/length for
individual sperm heads of each analysis were assessed by GLM-ANOVA for effects of
bulls, replications and technicians. The coefficient of variation was recorded
for each analysis and across replications. The mean coefficients of variation
within and between analyses were compared between technicians by GLM-ANOVA. No
differences (p > 0.1) between technicians were found between or among bulls for
area (29.63 vs. 29.26 micron 2), perimeter (23.73 vs. 23.86 microns), length
(8.73 vs. 8.71 microns), width (4.47 vs. 4.46 microns), or width/length (0.51 vs.
0.51). No differences (p > 0.1) between replicates for sperm head dimension were
detected within or among bulls for either technician. No intra- or inter-analysis
differences (p > 0.1) between technicians on CVs were observed. The mean intra
analysis CVs for all bulls for both technicians were area = 6.9%, perimeter =
4.9%, length = 4.5%, width = 5.6% and width/length = 6.5%. The mean interanalysis
CVs for both technicians were area = 3.0%, perimeter = 2.4%, length = 2.0%, width
= 2.0%, and width/length = 1.7%. The results indicate that ASMA is a repeatable
and objective method of assessing bull sperm head morphometry within and between
technicians. No differences between replications were detected, and hence
replicate analyses are not necessary to acquire accurate morphometric data.
PMID- 10194639
TI - Co-localization of HP1 and TP1 transcripts in human spermatids by double electron
microscopy in situ hybridization.
AB - Nuclear changes in the basic nucleoprotein complement occur during spermiogenesis
in man. Somatic type histones are displaced by transition proteins which are
replaced themselves by protamines, the major nuclear proteins present in late
spermatids and sperm nuclei. Sense and antisense 35S-labelled riboprobes, coding
respectively for human transition protein 1 (TP1) and protamine 1 (HP1), were
synthesized with modified specific oligonucleotides and were used for light
microscopy in situ hybridization. A double EM in situ hybridization was performed
using a digoxigenin-labelled probe for TP1 and a biotin-labelled probe for HP1,
and hybrids were revealed, respectively, with specific antibodies coupled to
colloidal gold particles of different sizes (10 nm and 15 nm). For both types of
transcripts, histological study revealed a specific distribution of the silver
grains in the adluminal region of the seminiferous tubules where spermatids are
localized. Quantitative ultrastructural analysis of the nuclear and cytoplasmic
labelling densities for the mRNAs coding for TP1 and HP1 showed that the
transcripts were found in both the nucleus and cytoplasm of round spermatids and
persisted until the elongation phase. Transcripts accumulated in the spermatid
cytoplasm without any particular cellular compartmentalization. At the end of the
spermatid elongation phase, the disappearance of TP1 and HP1 transcripts may be
related to the arrest of transcriptional activity, while the deposition of
transition proteins and protamines occurs successively within spermatid nuclei.
PMID- 10194640
TI - Degeneration of the seminiferous epithelium with ageing is a cause of
spermatoceles?
AB - A spermatocele refers to the cystic accumulation of semen in the male
reproductive tract. Although it is thought to be caused by narrowing of the lumen
of the excurrent duct with resultant cystic dilatation of the duct, the
pathogenesis of the narrowing remains unknown. In the present study, we
histologically examined spontaneous spermatoceles in C3H/He mice to elucidate the
pathogenesis of the lesions. Testes, efferent ducts, epididymides and vas
deferens obtained from young and aged C3H/He mice were embedded in plastic for
histological observation at the light microscopic level. It was found that
spontaneous spermatoceles were localized in the rete testis and efferent ducts of
aged mice, as seen in man. The dilated rete testis and efferent ducts contained
many degenerated and aggregated germ cells derived from the exfoliated
seminiferous epithelium in the aged testis. In particular, it was noted that the
agglutinated germ cells obstructed the narrow lumen of the efferent ducts,
resulting in the failure of transport of germ cells to the caput epididymis, and
spermatoceles were consistently found in the region between the rete testis and
the obstructed site in the efferent ducts. However, no inflammatory cell
infiltration, traumatic injury or spermatic granulomas were found in the occluded
region. These results suggest that agglutinated germ cells may occupy the narrow
lumen of the efferent ducts, resulting in the formation of a spermatocele. It may
be that a senile change to the seminiferous epithelium, which releases immature
germ cells into the lumen of the seminiferous tubules, is the cause of this type
of spermatocele.
PMID- 10194641
TI - Interstitial cell tumour and germ cell tumour with carcinoma in situ in rabbit
testes.
AB - Simultaneous occurrence of a well-demarcated interstitial cell tumour and an
intratubular seminoma-like tumour, which was beginning to invade peritubular
areas, in the contralateral testes of a 3-year-old Dutch-Belted rabbit is
described. Morphological hallmarks of carcinoma in situ, which have not been
reported previously for the rabbit, were observed in association with the
seminoma. These observations indicate that carcinoma in situ, preceding a
seminoma-like tumour, occurs in the rabbit and that the rabbit may serve as a
practically useful animal model for studying testicular germ cell neoplasia.
PMID- 10194642
TI - The effects of feeding an Asian or Western diet on sperm numbers, sperm quality
and serum hormone levels in cynomolgus monkeys (Macaca fascicularis) injected
with testosterone enanthate (TE) plus depot medroxyprogesterone acetate (DMPA).
AB - The aim of this study was to elucidate the effects of an Asian diet compared to a
Western diet on sperm numbers and quality, and serum hormones in cynomolgus
monkeys (Macaca fascicularis) injected with testosterone enanthate (TE) plus
depot medroxyprogesterone acetate (DMPA). Thirty male monkeys were divided into
three groups of ten animals each. The first group (control) was fed with standard
diet 'monkey chow' (9% fat, 13% protein, 78% carbohydrate); the second group was
fed an 'asian' diet (15% fat, 15% protein, 70% carbohydrate); the third group was
fed a 'Western' diet (35% fat, 25% protein, 40% carbohydrate). These diets were
administered from the beginning (adaptation) until the experiment was terminated.
Three months after the adaptation period, all groups were injected with 20 mg TE
(once per week) and 25 mg DMPA (once every 6 weeks) for 18 weeks, while TE
injections were continued for another 6 weeks. There were no differences in sperm
numbers and quality, or in hormone levels between the first and second groups. In
both of these groups azoospermia was achieved in 100% of animals, while in the
third group only 70% achieved azoospermia. In all 3 groups, spermatozoa were once
again detectable by week 33. However, by the end of the study at week 39, sperm
numbers in the first and second groups reached only severe oligozoospermia (two
animals remained azoospermic in the first group) while in the third group,
numbers had returned to normozoospermia. The quality of spermatozoa during and
after the treatment in the third group was better than in the first and second
groups. Hormone concentrations decreased more rapidly in both the first and
second groups, compared to the third group, while the recovery period was slower
in the first and second groups, compared to the third group. It is concluded that
different formula diets result in differential decreases in sperm numbers and
quality, and in hormone concentrations in M. fascicularis injected with TE in
combination with DMPA. Animals fed with either monkey chow or an Asian diet
exhibited more severe and prolonged decreases in these parameters than did
animals fed with a Western diet.
PMID- 10194643
TI - Screening for Chlamydia trachomatis and Ureaplasma urealyticum infection in semen
from asymptomatic male partners of infertile couples prior to in vitro
fertilization.
AB - In a prospective study, the prevalence of infection with Chlamydia trachomatis
and Ureaplasma urealyticum was evaluated in the semen of 92 asymptomatic male
partners of infertile couples using polymerase chain reaction and culture,
respectively. The results were compared with the detection of serologically
specific antibodies. U. urealyticum and C. trachomatis were detected in 12 (13%)
and 10 (10.8%) of the tested ejaculates, respectively. One mixed infection was
detected. No correlation was found between detection of the pathogens in
ejaculates and the presence of specific antibodies in serum. This study therefore
confirms the limited diagnostic value of serological analysis to ascertain
infection with C. trachomatis or U. urealyticum. The high frequency of detection
of these pathogens among asymptomatic male partners of infertile couples
emphasizes their potential role in the impairment of male fertility, and the need
for sensitive and specific detection methods to prevent infection of the early
embryo when using new reproductive techniques such as zona pellucida hatching or
intracytoplasmic microinjection.
PMID- 10194644
TI - Manipulation of postnatal testosterone levels affects phallic and clitoral
development in infant rhesus monkeys.
AB - Male primates exhibit marked elevation of circulating testosterone levels during
the early postnatal period. The aim of this project was to test whether
experimental manipulation of circulating testosterone levels in male and female
infant rhesus monkeys affected development of the external genitalia during the
first six months of life. Four groups of infants were studied. Seven control male
infants exhibited high circulating testosterone levels during the first three
months of life. Seven males were treated with a GnRH agonist (avorelin) from the
first week of life onwards, which suppressed the postnatal testosterone surge.
Ten control females exhibited low circulating testosterone levels during the
early postnatal period. Administration of testosterone to 10 females resulted in
high circulating levels in these infants. Fortnightly blood samples and genital
measurements were taken from all infants during the first six months of life.
Growth of the penis of avorelin-treated males was significantly retarded when
compared to control males. Average length of the penis at six months of age was
significantly (p = 0.012) smaller for avorelin-treated males (25.2 +/- 2.8 mm)
than for control males (37.3 +/- 3.0 mm). Avorelin-treated males attained only
around 50% detachment of the prepuce from the glans of the penis, while control
males averaged 90% detachment. Treatment of females with testosterone resulted in
significant growth of the clitoris in comparison to control females. The growth
rates of the penis of control males and clitorides of testosterone-treated
females were similar and greatest during the first two months of life. Gain in
body weight was not affected by either hormonal manipulation. It is concluded
that manipulation of circulating testosterone levels during the early postnatal
period affects penile and clitoral development of infant rhesus monkeys. This
postnatal period may therefore represent an important stage in penile development
in primates.
PMID- 10194645
TI - Photoperiodic time measurement in insects: a review of clock models.
AB - Based on analyses of responses of insects and mites to a wide range of diel and
nondiel experimental light-dark schedules, a variety of models have been
developed for the photoperiodic clocks in these species by nearly as many
investigators. According to some of these models, the photoperiodic clock is
based on a mechanism separate from the circadian system, that is, a so-called
"hourglass." According to other models, the clock is based on one or more
circadian oscillators that may be coupled to each other and that may or may not
show a certain degree of damping. In this context, a rapidly damping oscillator
could be regarded as an hourglass. The present article gives an overview of the
many different clock models and their philosophies, and it makes comparisons
among them to provide a better understanding about how these models are related,
if at all, and why the double circadian oscillator model is the most favored
model at present.
PMID- 10194646
TI - Photoperiodic control of the rat pineal arylalkylamine-N-acetyltransferase and
hydroxyindole-O-methyltransferase gene expression and its effect on melatonin
synthesis.
AB - Photoperiodic changes of pineal melatonin (MEL) profile are accompanied by
parallel changes of arylalkylamine-N-acetyltransferase (AA-NAT) activity. In the
present study, the authors investigated, for the first time, whether two other
important variables of pineal metabolism, AA-NAT and hydroxyindole-O
methyltransferase (HIOMT) gene expression, also may be affected by the
photoperiod. Evening rises in AA-NAT and HIOMT mRNA and in circulating MEL
occurred concomitantly with an increased delay from dark onset as scotophase
shortened. On the opposite, the morning declines of all three variables occurred
with different kinetics but were locked to light onset. These observations
demonstrate that the daily rhythms in AA-NAT and HIOMT gene expression are
modulated by the photoperiod and bring further evidence in favor of nor
adrenaline as the possible link between the endogenous clock and MEL.
Interestingly, the duration of the nocturnal peak in HIOMT mRNA was positively
correlated with HIOMT activity. In conclusion, this study adds two important
links to the chain of mechanisms involved in the photoperiodic control of pineal
metabolism. First, photoperiodic modulation of the MEL rhythm primarily results
from changes in the AA-NAT gene expression. Second, the photoperiodic regulation
of HIOMT activity occurs at the transcriptional level.
PMID- 10194647
TI - Melatonin suppression by light in humans is maximal when the nasal part of the
retina is illuminated.
AB - This study investigated whether sensitivity of the nocturnal melatonin
suppression response to light depends on the area of the retina exposed. The
reason to suspect uneven spatial sensitivity distribution stems from animal work
that revealed that retinal ganglion cells projecting to the suprachiasmatic
nuclei (SCN) are unequally distributed in several species of mammals. Four
distinct areas of the retinas of 8 volunteers were selectively exposed to 500 lux
between 1:30 a.m. and 3:30 a.m. Saliva samples were taken before, during, and
after light exposure in 1-h intervals. A significant difference in sensitivity
was found between exposure of the lateral and nasal parts of the retinas, showing
that melatonin suppression is maximal on exposure of the nasal part of the
retina. The results imply that artificial manipulation of the circadian pacemaker
to alleviate jet lag, to improve alertness in shift workers, and possibly to
treat patients suffering from seasonal affective disorder should encompass light
exposure of the nasal retina.
PMID- 10194648
TI - Melatonin suppression by illumination of upper and lower visual fields.
AB - As a guide to optimizing the geometry of bright light treatment, 12 healthy
subjects were studied three times in the laboratory from 11 p.m. to 2 a.m. On
three evenings, in counterbalanced orders, subjects received 500 lux in the upper
visual field, 500 lux in the lower visual field, or 5 lux while watching
television. In the upper visual field, 500 lux significantly suppressed
melatonin, as compared to 500 lux in the lower visual field or to 5 lux. In the
lower visual field, 500 lux produced intermediate suppression of borderline
significance. The results suggest that bright light treatment of depression or
circadian phase disorders might be most effective when applied in the upper
visual field.
PMID- 10194649
TI - A reexamination of the role of GABA in the mammalian suprachiasmatic nucleus.
AB - Three independent electrophysiological approaches in hypothalamic slices were
used to test the hypothesis that gamma-amino butyric acid (GABA)A receptor
activation excites suprachiasmatic nucleus (SCN) neurons during the subjective
day, consistent with a recent report. First, multiple-unit recordings during
either the subjective day or night showed that GABA or muscimol inhibited firing
activity of the SCN population in a dose-dependent manner. Second, cell-attached
recordings during the subjective day demonstrated an inhibitory effect of bath-
or microapplied GABA on action currents of single SCN neurons. Third, gramicidin
perforated-patch recordings showed that bicuculline increased the spontaneous
firing rate during the subjective day. Therefore, electrophysiological data
obtained by three different experimental methods provide evidence that GABA is
inhibitory rather than excitatory during the subjective day.
PMID- 10194650
TI - Serotonin agonist quipazine induces photic-like phase shifts of the circadian
activity rhythm and c-Fos expression in the rat suprachiasmatic nucleus.
AB - Nonphotic stimuli can reset and entrain circadian activity rhythms in hamsters
and mice, and serotonin is thought to be involved in the phase-resetting effects
of these stimuli. In the present study, the authors examined the effect of the
serotonin agonist quipazine on circadian activity rhythms in three inbred strains
of rats (ACI, BH, and LEW). Furthermore, they investigated the effect of
quipazine on the expression of c-Fos in the mammalian circadian pacemaker, the
suprachiasmatic nucleus (SCN). Quipazine reduced the amount of running wheel
activity for 3 h after treatment, however, no long-term changes in tau and in the
activity level were observed. More important, quipazine induced significant phase
advances of the activity rhythm and c-Fos production in the SCN at the end of the
subjective night (Circadian Time [CT] 22), whereas neither phase shifts nor c-Fos
induction were observed during the subjective day. Quipazine injections also
resulted in moderate phase delays at the beginning of the subjective night (CT
14). A similar phase-response characteristic typically can be observed for photic
stimuli. By contrast, nonphotic stimuli normally produce phase advances during
the subjective day. The present results suggest species differences between the
hamster and the rat with respect to the serotonergic action on circadian
timekeeping and indicate that serotonergic pathways play a role in the
transmission of photic information to the SCN of rats.
PMID- 10194651
TI - A delayed rectifier current is modulated by the circadian pacemaker in Bulla.
AB - Basal retinal neurons of the marine mollusc Bulla gouldiana continue to express a
circadian modulation of their membrane conductance for at least two cycles in
cell culture. Voltage-dependent currents of these pacemaker cells were recorded
using the whole-cell perforated patch-clamp technique to characterize outward
currents and investigate their putative circadian modulation. Three components of
the outward potassium current were identified. A transient outward current (IA)
was activated after depolarization from holding potentials greater than -30 mV,
inactivated with a time constant of 50 ms, and partially blocked by 4
aminopyridine (1-5 mM). A Ca(2+)-dependent potassium current (IK(Ca)) was
activated by depolarization to potentials more positive than -10 mV and was
blocked by removing Ca2+ from the bath or by applying the Ca2+ channel blockers
Cd2+ (0.1-0.2 mM) and Ni2+ (1-5 mM). A sustained Ca(2+)-independent current
component including the delayed rectifier current (IK) was recorded at potentials
positive to -20 mV in the absence of extracellular Na+ and Ca2+ and was partially
blocked by tetraethylammonium chloride (TEA, 30mM). Whole-cell currents recorded
before and after the projected dawn and normalized to the cell capacitance
revealed a circadian modulation of the delayed rectifier current (IK). However,
the IA and IK(Ca) currents were not affected by the circadian pacemaker.
PMID- 10194653
TI - Addressing the heart failure management gap.
PMID- 10194652
TI - Aging affects the ocular circadian pacemaker of Aplysia californica.
AB - The eye of Aplysia has been used to explore various aspects of circadian rhythms.
The authors discovered that age has profound effects on the circadian rhythm of
nerve impulses from the eye. With age, there was a significant decrease in the
amplitude of the rhythm. The decrease appeared to be continuous over the life
span of the animal and was observed both in vitro and in vivo. The free-running
period and phase angle of the rhythm steadily increased with age, indicating that
the pacemaker itself was affected by age. Rates of transcription and translation
were significantly increased with age, suggesting that age-associated alterations
of the pacemaker may occur through changes in macromolecular synthesis.
Interestingly, eyes from some older (> or = 10 months) animals had "cloudy"
lenses (cataracts). Highly damped or arrhythmic rhythms always were seen in eyes
with cloudy lenses. Morphology of eyes with cloudy lenses indicated severe
retinal degeneration. No such degeneration was observed in eyes with clear lenses
that were used in the analysis of the rhythm with age.
PMID- 10194654
TI - Prescribing and emergency admissions for heart failure in greater Glasgow.
AB - BACKGROUND: We sought to determine whether there is an association between the
rate of prescription of angiotensin-converting enzyme (ACE) inhibitors and the
rate of hospitalization for heart failure. METHODS AND RESULTS: We conducted a
cross-sectional study linking prescribing data with hospital admission data from
215 primary health care practices in Greater Glasgow, United Kingdom. We obtained
numbers of prescriptions of diuretics. ACE inhibitors, and digoxin and numbers of
admissions for heart failure. The mean practice rate of diuretic prescription was
0.7 per patient per year, the mean practice rate of ACE inhibitor prescription
was 0.06 per patient per year, the mean practice rate of digoxin prescription was
0.09 per patient per year, and the mean practice rate of admission for heart
failure was 3.29 per 1,000 patients per year. There was a strong and significant
association between the rate of diuretic prescription and the rate of digoxin
prescription. There was only a moderate inverse association between the ratio of
ACE inhibitor to diuretic prescriptions and the rate of admissions for heart
failure. CONCLUSIONS: ACE inhibitors are underused. Rates of diuretic and digoxin
prescriptions correlate strongly and are presumably both markers for similar
cardiovascular morbidity. There was no evidence that ACE inhibitors modulated the
rate of heart failure admissions.
PMID- 10194655
TI - Electrical and hemodynamic correlates of the maximal rate of pressure increase in
the human left ventricle.
AB - BACKGROUND: The rate of left ventricular (LV) pressure increase (LV + dP/dt) may
be related to QRS duration, as well as to a number of hemodynamic parameters.
METHODS AND RESULTS: We studied the relation between basal LV + dP/dt and QRS
duration in 43 patients with normal LV function and 81 patients with heart
failure undergoing diagnostic catheterization. We also examined the relationship
between LV + dP/dt and heart rate, as well as measures of both LV preload and
afterload. In patients with normal LV function, there was a strong relationship
between basal LV + dP/dt and resting heart rate, whereas the relationship with
QRS duration was of borderline significance. In patients with heart failure, the
relationship with heart rate was lost; however, LV systolic pressure, QRS
duration, and LV end-diastolic pressure all made significant contributions to a
model predicting LV + dP/dt. CONCLUSIONS: These data show a strong relationship
between resting heart rate and LV + dP/dt in the healthy human LV. In patients
with heart failure, the relationship with heart rate is not maintained; however,
there is a systematic relationship between LV + dP/dt and both the time-course of
the electrical activation and measures of LV loading conditions.
PMID- 10194656
TI - Reversal of peripheral microvascular dysfunction during long-term treatment with
the angiotensin-converting enzyme inhibitor fosinopril in congestive heart
failure.
AB - BACKGROUND: Treatment with angiotensin-converting enzyme (ACE) inhibitors in
congestive heart failure (CHF) improves cardiac and peripheral hemodynamic
function and exercise performance. However, studies on the effects of long-term
treatment with an ACE inhibitor on the neurogenic and nonneurogenic regulation
and structural microangiopathy of the peripheral microvasculature in CHF are
lacking. METHODS AND RESULTS: We investigated the effect of 12 weeks of treatment
with the ACE inhibitor fosinopril on peripheral microvascular function in a
double-blind, placebo-controlled study of 12 patients treated with fosinopril and
10 patients treated with placebo. All had moderate CHF. Microvascular blood flow
and resistance were calculated after application of the local isotope washout
method in relaxed and nonrelaxed calf vascular beds in the supine position and
during head-up tilt. Skeletal muscle vascular resistance was reduced in the
fosinopril group (46 +/- 6 to 30 +/- 1 mm Hg.mL-1.100 g.min +/- standard error; P
< .05) and differed compared with the effect of placebo (P < .05) where no change
was seen (37 +/- 11 to 55 +/- 13 mm Hg.mL-1.100 g.min; not significant [NS]).
Also, skin minimal vascular resistance was reduced during fosinopril treatment
(13 +/- 0.6 to 11 +/- 0.7 mm Hg.mL-1.100 g.min; P < .05) and differed compared
with the effect of placebo (P < .05) with absence of change (12 +/- 1.6 to 14 +/-
1.4 mm Hg.mL-1.100 g.min; NS). CONCLUSIONS: These results suggest that long-term
ACE inhibitor treatment with fosinopril in patients with CHF improves hemodynamic
status to as far as the peripheral microvascular level in both the relaxed and
nonrelaxed microcirculation of the lower leg.
PMID- 10194657
TI - Effects of dobutamine on ischemic vasodilation of the forearm in patients with
severe congestive heart failure.
AB - BACKGROUND: The significant changes that occur in the peripheral circulatory
system in heart failure are well known. Although the central hemodynamic effects
of dobutamine have been well described, data on its effect on peripheral vascular
function in patients with severe left ventricular dysfunction are limited.
METHODS AND RESULTS: Resting and hyperemic forearm blood flow and resistance were
measured using forearm venous occlusion plethysmography in patients with advanced
congestive heart failure (CHF) before and during the infusion of increasing doses
of dobutamine. Total hyperemia was also calculated. We studied eight patients
with New York Heart Association classes III to IV CHF who had a mean age of 62 +/
5 years and a mean ejection fraction of 17.4% +/- 2.9%. Resting forearm blood
flow increased from 2.3 +/- 0.2 to 3.4 +/- 0.4 mL/min/100 mL during peak
dobutamine infusion (P < .05). Resting forearm vascular resistance decreased from
39 +/- 3 to 29 +/- 4 units (P < .02). Peak hyperemic forearm blood flow increased
from 25 +/- 3 to 34 +/- 6 mL/min/100 mL of tissue (P < .02) and peak hyperemic
vascular resistance decreased from 3.7 +/- 0.4 to 2.9 +/- 0.3 units (P < .01).
Total hyperemia increased from 14.3 +/- 1.9 to 19.4 +/- 2.4 mL/100 mL (P < .01).
CONCLUSIONS: The data show that in patients with advanced CHF, intravenous
dobutamine not only increases resting forearm blood flow and decreases resting
forearm vascular resistance, but augments the reactive hyperemic flow and
improves the vasodilatory response of the forearm vessels to transient ischemic
occlusion. The underlying mechanism for this response and its clinical
significance remain to be identified.
PMID- 10194658
TI - Intravenous thyroid hormone supplementation in heart failure with cardiogenic
shock.
AB - BACKGROUND: Thyroid hormone level abnormalities commonly exist in severe heart
failure and may be of prognostic value. The therapeutic potential of using
thyroid hormone for cardiogenic shock resulting from progressive heart failure
has not been previously delineated. We sought to evaluate the role of an
intravenous infusion of thyroxine as an adjunct to conventional inotropic agents
and intra-aortic balloon counterpulsation in patients with severe heart failure
with cardiogenic shock. METHODS AND RESULTS: We studied 10 consecutive patients
with severe systolic heart failure that progressed to a cardiogenic shock state
unresponsive to conventional pharmacological inotropic measures. Intravenous
thyroxine (20 micrograms/h) was used as an adjunctive salvage measure after the
failure of conventional pharmacological and mechanical support by intra-aortic
balloon pump. The invasive hemodynamic profile (right atrial pressure, pulmonary
capillary wedge pressure, cardiac index, mean arterial pressure), overall
clinical status, core temperature, renal function, and tachyarrhythmias were
compared before and sequentially at 6, 24, and 36 hours after the initiation of
thyroxine administration. Long-term outcome was also defined. All patients had
statistically significant improvements in cardiac index, pulmonary capillary
wedge pressure, and mean arterial pressure at 24 and 36 hours post-initiation of
thyroxine. No sustained tachyarrhythmias were seen during the thyroxine infusion.
In 9 of 10 patients who underwent left ventricular assist device placement and/or
heart transplantation, the use of thyroxine served as an effective adjunctive
measure to allow transitioning to definitive surgical therapy. The 6-month and 1
year cohort survival rates, achieved by the transition to surgical therapy, were
90% and 80%, respectively. CONCLUSION: The beneficial hemodynamic properties of
intravenous thyroid hormone can be effectively used in otherwise terminal
situations of cardiogenic shock, and in such situations, the use of thyroid
hormone can serve as a pharmacological adjunct to a definite surgical
intervention. Further studies in larger numbers of patients might be warranted to
confirm these findings.
PMID- 10194659
TI - Differential roles of endothelin-1 in the development of secondary pulmonary
hypertension in patients with left heart failure with or without acute
exacerbation.
AB - BACKGROUND: The aim of this study was to investigate the contribution of
endothelin-1 (ET-1) to the development of secondary pulmonary hypertension (PH)
in patients with left heart failure (HF). METHODS AND RESULTS: The subjects were
40 patients with left HF with (group 1; n = 20) and without (group 2; n = 20)
acute exacerbation. Before treatment, the ET-1 level in the pulmonary capillary
wedge region was three times greater in patients of group 2 than group 1,
although there was no significant difference in mean pulmonary artery pressure
(mPAP) or pulmonary vascular resistance index (PVRI) between the two groups.
Also, the ET-1 level significantly correlated with mPAP and PVRI for both groups,
but with different slopes of the regression lines. After treatment of group 1,
the extent of reduction in the ET-1 level significantly correlated with that in
mPAP and in PVRI, whereas the ET-1 level itself correlated with mPAP, with the
regression lines approximating those of group 2. CONCLUSIONS: Our findings
suggest that ET-1 may have differential roles in the development of secondary PH
in patients with left HF with or without acute exacerbation.
PMID- 10194660
TI - Right ventricular phenotypic characteristics in subjects with primary pulmonary
hypertension or idiopathic dilated cardiomyopathy.
AB - BACKGROUND: Studies of animal models and human subjects with cardiomyopathies
suggest that cardiac myocyte and ventricular chamber remodeling show distinct
phenotypic characteristics that may be dependent on specific signaling pathways.
METHODS AND RESULTS: In this study, we characterize right ventricular (RV)
chamber size, end-diastolic thickness, myocardial mass, and ejection fraction
(EF) in human subjects with chronic heart failure from primary pulmonary
hypertension (PPH; n = 10) and idiopathic dilated cardiomyopathy (IDC; n = 10).
Subjects underwent gated cardiac magnetic resonance imaging (MRI), and the RVs
were phenotypically classified based on the presence or absence of hypertrophy
(increased mass), systolic dysfunction (reduced EF), and degree of wall thickness
(concentric v eccentric pattern of hypertrophy). Within this schema, five
abnormal phenotypes could be identified. In PPH subjects, in whom the RV is
subjected to the uniform insult of chronic pressure overload, four different
abnormal phenotypes were identified. CONCLUSIONS: These data indicate that
distinct structural/functional ventricular chamber phenotypes may be classified
by MRI, and that a uniform insult can result in multiple RV phenotypes.
PMID- 10194661
TI - Vascular alterations during the development and progression of experimental heart
failure.
AB - BACKGROUND: Congestive heart failure (HF) is a multifactorial and progressive
condition associated with multiple systemic and vascular alterations. The onset
and progression of these alterations and the cause of the condition remain
undefined. The main purpose of the present study was to help understand the
temporal evolution of vascular alterations and their contribution to the
pathogenesis of HF. Vascular reactivity to angiotensin II (Ang II) and
norepinephrine (NE), as well as circulating and local angiotensin-converting
enzyme (ACE) activity, were assessed in the Syrian cardiomyopathic hamster (SCH)
model. METHODS AND RESULTS: We have shown previously that in 2-month-old SCH
animals that had not yet developed the clinical manifestations of HF, the
contractile response of aortic rings to Ang II was markedly enhanced compared
with normal animals. In addition, SCHs showed increased ACE activity in aortic
tissue. To assess the relevance of these findings to the development and
progression of HF, the temporal evolution of the contractile response of aortic
rings to Ang II and NE was evaluated in hamsters at 2, 6, and 11 months of age.
Age-matched normal hamsters were used as controls. Within the SCH group, the
maximal contraction induced to 10 mumol/L of NE in 2- and 11-month-old animals
was similar, but significantly greater than in the age-matched controls (for 2
month-old animals; 1.43 +/- 0.21 g in SCHs v 1.04 +/- 0.15 g in controls; P < .05
and for 11-month-old animals; 1.41 +/- 0.14 g in SCHs v 1.06 +/- 0.07 g in
controls; P < .05). The drug concentrations necessary to obtain 50% of the
maximal response from the NE concentration-response curves were similar for SCHs
and controls at all ages tested. In contrast, the contractility induced by 0.1
mumol/L of Ang II increased progressively in cardiomyopathic animals from 2 to 11
months of age (from 1.3 +/- 0.1 to 1.8 +/- 0.2 g; n = 9; P < .05). In age-matched
normal hamsters, the contractile response to Ang II (0.9 +/- 0.1 g) did not vary
with age. These findings were observed concomitantly with an increased ACE
activity in plasma (18.65 +/- 1.77 nmol/mg x min in controls v 26.5 +/- 1.79
nmol/mg x min in SCHs; P < .05; n = 7) and in heart tissue (0.244 +/- 0.016
nmol/mg x min in controls v 0.563 +/- 0.027 nmol/mg x min in SCHs; P < .05; n =
20) of 11-month-old SCHs. CONCLUSIONS: These results suggest that, in young
animals, increased vascular response to elevated levels of NE and hyperreactivity
to Ang II could be critical factors in the development and progression of HF.
Indeed, Ang II-induced contractility, as well as plasma and heart ACE activity,
are good predictors of the progression and severity of HF.
PMID- 10194662
TI - Heart failure disease management: a critical review.
AB - BACKGROUND: Despite major advances in the pharmacotherapy of heart failure,
hospitalization rates remain high, owing in large part to a multitude of
psychosocial, behavioral, and financial factors that serve as barriers to
effective compliance with prescribed treatment. To deal with these issues, many
centers have adopted a multidisciplinary approach to heart failure disease
management. METHODS AND RESULTS: A systematic review of the literature was
conducted using the Medline database supplemented by reference lists from
published articles. From 1983 to 1998, 16 studies describing multidisciplinary
heart failure disease management programs were published in the English language
literature. Of these, 10 were nonrandomized, observational studies and 6 were
randomized clinical trials. All studies reported significant benefits in terms of
reducing hospital utilization, and several studies reported improved quality of
life, functional capacity, patient satisfaction, and compliance with diet and
medications. In all studies in which a cost analysis was performed, heart failure
disease management programs were found to be cost-effective. The limitations of
the current data include concerns about the generalizability of published
findings to the large and heterogenous population of patients with heart failure
in the community, the feasibility of translating specific disease management
programs into diverse practice environments, uncertainty about how to design and
implement a maximally cost-effective heart failure disease management strategy,
and how to best tailor the treatment program to the needs of each individual
patient. The impact of heart failure disease management programs on survival is
also unknown. CONCLUSION: Based on currently available data, heart failure
disease management programs appear to be a cost-effective approach to reducing
morbidity and enhancing quality of life in selected patients with heart failure.
However, additional study is needed involving larger and more diverse populations
to define the optimal approach to heart failure disease management.
PMID- 10194663
TI - Measurement of bile salt hydrolase activity from Lactobacillus acidophilus based
on disappearance of conjugated bile salts.
AB - Bile salt hydrolase activity of Lactobacillus acidophilus was measured based on
the disappearance of sodium glycocholate and sodium taurocholate from the
reaction mixture using HPLC. The amount of sodium glycocholate and sodium
taurocholate that disappeared was proportional to the amount of sodium cholate
that appeared in the mixture as detected by HPLC. Sodium glycocholate did not
precipitate at the enzyme reaction conditions (37 degrees C and pH 5.4) for
determining bile salt hydrolase activity. The bile salt hydrolase assay was
insensitive to low oxidation-reduction potential when measuring bile salt
hydrolase from L. acidophilus, an intestinal microorganism. However, EDTA and
freezing temperatures were necessary to maintain stability of the partially
purified enzyme during storage.
PMID- 10194664
TI - Bile salt hydrolase activity of three strains of Lactobacillus acidophilus.
AB - Three strains of Lactobacillus acidophilus, two from human intestinal origin (016
and L1) and one from porcine intestinal origin (ATCC 43121), were tested for
their bile salt deconjugation activity. The L. acidophilus ATCC 43121 had more
deconjugating activity of both sodium glycocholate and sodium taurocholate at pH
6.5 than did either L. acidophilus 016 or L1. The activity of intracellular bile
salt hydrolase found in strain ATCC 43121 was 14-fold higher than that in either
of the other two strains. The optimum pH for deconjugation of sodium glycocholate
was between 4 and 5.5 for all three strains. For deconjugation of sodium
taurocholate, the optimum pH was between 3.5 and 4.5 for strains L1 and ATCC
43121 and was between pH 5 and 6 for strain O16. The molecular mass of the enzyme
in all three strains of L. acidophilus was estimated to be 126 kDa by Sephadex G
200 gel filtration. All three strains exhibited more bile salt hydrolase activity
towards sodium glycocholate than towards sodium taurocholate.
PMID- 10194665
TI - Proposing sequences for peptides derived from whey fermentation with potential
bioactive sites.
AB - In fed-batch fermentation by Kluyveromyces marxianus var. marxianus, whey-soluble
proteins were converted into oligopeptides. To assess whether bioactive peptides
could be produced during whey fermentation, K. marxianus was cultured in batch in
deproteinized media containing 5 or 15% (wt/vol) dehydrated whey for 20 h and
then was in fed-batch mode for 50 h. After harvesting the biomass (25,000 x g, 15
min), at 6-h intervals, the wort was analyzed to determine protein consumption
and oligopeptide production by HPLC. The proteins in the wort showed an
oscillatory degradation with a constant increase in the production of
oligopeptides. Four major peaks were collected and were analyzed by API mass
spectroscopy. Sequences of fermented peptides were compared with sequences of
known bioactive peptides. On the basis of their molecular weights, two amino acid
sequences were proposed. The presence of sites containing the peptide sequence of
beta-lactorphin (YLLF) suggests that these oligopeptides may have
antihypertensive properties.
PMID- 10194666
TI - Enhancement of the activity of novobiocin against Escherichia coli by
lactoferrin.
AB - The activity of novobiocin against Escherichia coli ATCC 25922 and three E. coli
strains that were isolated from cases of bovine mastitis was determined in
timekill studies in the presence of bovine lactoferrin. Lactoferrin alone did not
affect the growth of any of the strains of E. coli. A combination of 1.0 mg/ml of
lactoferrin and novobiocin at 1/16x minimum inhibitory concentration (MIC) was
bactericidal for E. coli ATCC 25922. When the concentration was increased to 3.0
mg/ml of lactoferrin, novobiocin was bactericidal at 1/64x MIC. Among the
mastitis strains tested, 6789 and 6806 were more susceptible to killing by
novobiocin than was strain 6800. Strains 6789 and 6806 were killed when treated
with novobiocin concentrations of 2, 1/2, and 1/4x MIC. When these strains were
also treated with lactoferrin at 3.0 mg/ml, there was a bacteriostatic effect at
novobiocin concentrations of 1/8 and 1/16x MIC for strains 6789 and 6800. Strain
6806 appeared to be more susceptible to the combination of lactoferrin and
novobiocin as was evidenced by a bactericidal effect over the 24-h testing
period. The combination treatment with cephapirin and lactoferrin showed that
there was a synergistic bactericidal effect against all of the E. coli strains
tested. These studies indicate that lactoferrin can potentiate the activity of
antibiotics against Gram-negative bacteria.
PMID- 10194667
TI - Effect of fatty liver on hepatic gluconeogenesis in periparturient dairy cows.
AB - The purpose of this study was to compare the hepatic enzyme activities of
gluconeogenesis between control cows and experimental cows that had been overfed
during the dry period to induce fatty liver postpartum. Blood and liver samples
were collected 1 wk before and 0.5, 1, 2, and 3 wk after parturition. Before
parturition, neither the serum nonesterified fatty acid nor the liver
triacylglycerol concentration differed between the two groups. After parturition,
these variables were higher in experimental cows than in control cows. Liver
glycogen was higher at 1 wk before parturition in experimental cows; sharply
decreased after parturition in both groups; and, at 1 wk after parturition, was
lower in experimental cows than in control cows. In the liver, activities of
phosphoenolpyruvate carboxykinase were significantly lower at 1 wk before and at
0.5 and 2 wk after parturition in experimental cows; in addition, the activities
tended to be lower at 1 wk after parturition. Activities of fructose 1,6
bisphosphatase tended to be lower, but activities of glucose 6-phosphatase tended
to be higher, at 0.5 wk after parturition in experimental cows than in control
cows. Our results suggest that, in fatty infiltrated liver, the rate of
gluconeogenesis is not optimal, which results in prolongation of lipolysis,
particularly during the first weeks after parturition.
PMID- 10194668
TI - Reproductive performance of dairy cows in various programmed breeding systems
including OvSynch and combinations of gonadotropin-releasing hormone and
prostaglandin F2 alpha.
AB - In Experiment 1, 308 Holstein cows were assigned randomly to four treatments: 1)
GnRH injection followed in 7 d by PGF2 alpha injection, then another GnRH
injection 33 h later, and artificial insemination (AI) 16 to 18 h after the
second GnRH injection; 2) GnRH injection followed in 7 d by PGF2 alpha injection
and AI only after detected estrus; 3) injections of PGF2 alpha 14 d apart, GnRH
injection 33 h after the second PGF2 alpha injection, and AI 16 to 18 h later;
and 4) injections of PGF2 alpha 14 d apart, AI only after detected estrus
following the second PGF2 alpha injection or, in the absence of detected estrus,
at 80 h after the second PGF2 alpha injection. In Experiment 2, 227 Holstein cows
were assigned randomly to two treatments: 1) GnRH injection followed in 7 d by
PGF2 alpha injection, then another GnRH injection 48 h later, and AI 16 to 18 h
after the second GnRH injection; and 2) GnRH injection followed in 7 d by PGF2
alpha injection and AI only after detected estrus. Although conception rates in
both experiments resulting from AI made after detected estrus either tended to be
greater or were consistently greater than those following GnRH injection and one
fixed-time AI, pregnancy rates were of greater magnitude after fixed-time AI
because of poor expression or detection of estrus.
PMID- 10194669
TI - Short communication: lack of stage-specific embryonic antigen-1 expression by
bovine embryos and primordial germ cells.
AB - The objective of this study was to determine whether stage-specific embryonic
antigen-1, a cellular marker commonly used to identify murine undifferentiated
embryonic cells, is also a useful marker for bovine pluripotent cells. Expression
of stage-specific embryonic antigen-1 was examined by indirect
immunohistochemistry on bovine preimplantation embryos and on primordial germ
cells contained in the genital ridge. Expression of stage-specific embryonic
antigen-1 was not observed in any of the cleavage-stage bovine embryos examined,
including one-cell, two-cell, four-cell, eight-cell, morula, and blastocyst
stages, nor in tissue sections of bovine genital ridges collected from embryos on
d 34, 37, and 40 of gestation. As expected, expression of stage-specific
embryonic antigen-1 was detected on murine preimplantation embryos and on murine
teratocarcinoma cells. Results of this study indicate that, unlike in the mouse,
stage-specific embryonic antigen-1 is not a useful cellular marker for
pluripotent bovine embryonic cells or bovine primordial germ cells.
PMID- 10194670
TI - Effect of applying lactic acid bacteria isolated from forage crops on
fermentation characteristics and aerobic deterioration of silage.
AB - Two selected strains, Lactobacillus casei FG 1 and Lactobacillus plantarum FG 10
that were isolated from forage crops were used as additives at 1.0 x 10(5) cfu/g
of fresh matter to alfalfa, Italian ryegrass, and sorghum, and their effect on
fermentation characteristics and aerobic deterioration of silage was studied. The
three silages treated with strains FG 1 or FG 10 were well preserved; had
significantly lower pH values, butyric acid, propionic acid, and ammonia N
concentrations, gas production, and dry matter losses; and had significantly
higher contents of residual water-soluble carbohydrates and lactic acid than did
the respective control silages. Yeast counts were high in all treated silages and
increased rapidly during aerobic exposure. As a result, treated silages spoiled
faster upon aerobic exposure than did the respective control silages. Most yeasts
isolated from deteriorated silages showed high tolerance to lactic acid but low
tolerance to butyric acid, and they were able to grow at low pH conditions and
assimilate lactic acid. The results confirmed that L. casei and L. plantarum
improved fermentation quality but did not inhibit the growth of silage yeast or
aerobic deterioration of the silage.
PMID- 10194671
TI - Metabolic and yield responses of multiparous Holstein cows to prepartum rumen
undegradable protein.
AB - The effects of concentration of rumen-undegradable protein (RUP) in prepartum
diets on performance and metabolic measures were determined. Pregnant,
nonlactating cows were assigned to one of three dietary treatments that differed
in concentrations of crude protein and RUP. The crude protein and RUP percentages
(dry matter basis) in the diets were 11.7 and 3.1%, 15.6 and 6.8%, and 20.6 and
10.6%, which were identified as low, medium, and high protein diets,
respectively. Dietary treatments were initiated 6 wk prior to expected calving
date and were fed until parturition. All cows were fed similar postpartum diets
through wk 10 of lactation. Prepartum intakes of dry matter and rumen-degradable
protein were similar among treatments. Yields of milk, protein, and fat were not
affected by prepartum RUP. Concentrations of plasma urea N in cows fed the medium
and high protein diets were elevated during the prepartum period even though
intakes of rumen-degradable protein were similar for cows on all treatments. Cows
fed the medium and high protein diets had greater prepartum concentrations of
Val, Ile, and Leu but not other essential amino acids in plasma. Dietary
treatments did not affect prepartum or postpartum contents of triglycerides in
liver or plasma nonesterified fatty acid concentrations. Thus, supplemental RUP
fed to cows for 6 wk prepartum affected protein metabolism but not measures of
energy metabolism.
PMID- 10194672
TI - Effect of micronizing full fat canola seed on amino acid disappearance in the
gastrointestinal tract of dairy cows.
AB - Ruminal and total tract digestion of the amino acids (AA) in full fat canola seed
was studied in two in situ experiments with three nonlactating, ruminally and
duodenally fistulated dairy cows. Whole, full fat canola seed was hand-cracked or
micronized (an infrared heat treatment) for 90 s and then studied in that form or
after grinding to pass a 1.25-mm sieve. In the first experiment, the four sample
types were ruminally incubated in nylon bags for up to 96 h. In the second
experiment, they were sealed in mobile nylon bags, incubated ruminally for 16 h,
placed in acidified pepsin for 1 h, and then inserted into duodenal cannulas for
passage through the intestine. Amino acids in the canola seed and in the residues
from in situ incubations were analyzed by HPLC. Micronization reduced ruminal
disappearance of total AA and essential AA from full fat canola seed. Degradation
kinetics from Experiment 1 indicated reduced soluble fraction and increased
slowly degradable fraction of both total AA and essential AA following
micronization. Micronization reduced disappearances of total AA and essential AA
from whole canola seed in the total digestive tract but did not affect total
tract digestion of total AA or essential AA in ground seed. Intestinal
disappearance of total AA and essential AA from both whole and ground full fat
canola seed were increased by micronization. Micronizing canola seed may be of
value in improving AA utilization in ruminants.
PMID- 10194673
TI - Effects of dietary crude protein concentration and degradability on milk
production responses of early, mid, and late lactation diary cows.
AB - Three experiments were conducted to investigate the effect of crude protein (CP)
concentration and ruminally undegraded protein (RUP) concentration on milk
production and composition of dairy cows at three different stages of lactation.
Experiments 1, 2, and 3 using 39, 40, and 39 Holstein cows were conducted for
cows in early (wk 4 to 14 postpartum), mid (wk 19 to 29), and late (wk 34 to 44)
lactation, respectively. Cows were assigned to one of four corn-based diets: high
CP, medium RUP (control); low CP, low RUP; low CP, medium RUP; and low CP, high
RUP. Percentages of CP in the high and low CP diets were, respectively, 17.4 and
15.2 for Experiment 1, 15.3 and 13.3 for Experiment 2, and 14.2 and 12.6 for
Experiment 3. The RUP concentrations (percentages of CP) for low, medium, and
high diets averaged 35.5, 41.4, and 46.5%, respectively. For Experiment 1,
production of milk, 4% fat-corrected milk, milk fat, and milk protein was
increased by the high protein diets versus the low protein diets. Production of
milk and fat-corrected milk increased linearly as RUP in the diet increased.
During Experiment 2, lactational responses were not affected by treatment. During
Experiment 3, dry matter intake, body weight, and body weight change increased
for cows fed the high protein diets versus those same measurements for cows fed
the low protein diets. Milk fat and milk protein percentage decreased linearly as
RUP in the diet increased. Because there was no effect of diet on milk
production, decreasing CP in diets fed to cows in mid or late lactation can
reduce the cost of the diet and waste N excreted from the cow.
PMID- 10194674
TI - Use of different dietary protein sources for lactating goats: milk production and
composition as functions of protein degradability and amino acid composition.
AB - To establish the effect of the nature of four different protein sources
[fababeans, 27.8% crude protein (CP); sunflower meal, 41.7% CP; corn gluten feed,
18.8% CP; and cottonseed, 18.3% CP] on milk protein production by goats, the
ruminal degradation of these feeds was studied as was the amino acid (AA)
composition of the original material and that of the undegradable fractions of
the protein sources. Four diets were designed; 20% of their protein was supplied
by each of the different sources. Four groups of 5 Granadina goats were used to
study the utilization of these diets for milk production. No significant
differences were observed in dry matter intake or milk production. The milk
produced by goats fed the diet containing sunflower meal had the lowest protein
concentration; the highest milk protein concentration was observed for goats fed
the diet containing corn gluten feed. From a multivariate analysis, it was
deduced that the quickly degradable protein fraction in the rumen and the
ruminally undegradable protein fraction were the components of the protein
sources most directly related to the milk protein produced. Given the similar AA
profiles of the undegradable fractions of the different protein sources, the
possible supplementation achieved from these ruminally undegradable fractions
must be established by the amount of protein supplied regardless of AA
composition.
PMID- 10194675
TI - Estimation of the digestible energy of ruminant feedstuffs by the combined bag
technique.
AB - The combined bag technique was used to estimate digestible energy of ruminant
feedstuffs. Samples of corn, barley, and sorghum grains; soybean and sunflower
meals; corn and wheat silages; and vetch and wheat hays were incubated in dacron
bags in the rumens of dairy cattle for 3 to 72 h. Bags containing residues after
12 h of ruminal incubation were introduced into the duodenum and recovered from
feces. Feeds and ruminal and intestinal residues were analyzed for dry matter
(DM), organic matter (OM), crude protein (CP), neutral detergent fiber, and
nonstructural carbohydrates. The effective ruminal degradability of OM was higher
in grains (639 g/kg of DM) and in protein supplements (609 g/kg of DM) than in
forages (373 g/kg of DM). For grains and forages, carbohydrates contributed most
of the degradable OM in the rumen, but, in protein supplements, about 50% of the
ruminally degradable OM originated from carbohydrate. For protein supplements,
54% of the OM that disappeared postruminally was CP, but, in the grains and
forage ingredients, CP contributed less than 20% of the postruminal OM that
disappeared. In grains and forages, 83% of total tract disappearance of OM was
from carbohydrates. For protein supplements, CP contributed 50% to overall OM
disappearance. The calculated energy equivalent of digested matter averaged among
feeds was 4.71 kcal/g. A high correlation was found between digestible energy
estimated by the combined bag technique and the respective National Research
Council values. The combined bag technique is a useful tool for the estimation of
digestible energy in feedstuffs.
PMID- 10194676
TI - Milk production and composition from cows fed wet corn distillers grains.
AB - Twelve lactating Holstein cows were utilized in a repeated switchback design to
evaluate milk production and milk fat composition responses to wet corn
distillers grains. Total mixed diets consisted of 31.4% corn silage, 18.4%
alfalfa hay, and either 50.2% of a concentrate mix that contained mostly corn and
soybean meal or 19.4% of a concentrate mix that contained mostly corn and 31.2%
wet corn distillers grains. The first 4 wk of each 6-wk period were for
adaptation to diets; data were collected during wk 5 and 6 of each period.
Although dry matter intake (22.1 vs. 19.7 kg/d) was lower when cows were fed the
wet corn distillers grains diet, milk production (30.7 vs. 30.8 kg/d) was similar
for cows fed both diets. Milk fat (3.60 vs. 3.85%) was slightly higher, and
protein (3.06 vs. 2.84%) was lower, when cows were fed the wet corn distillers
grains diet. Milk fat from cows fed wet corn distillers grains contained lower
concentrations of saturated fatty acids and higher concentrations of long-chain
and unsaturated fatty acids. The feeding of wet corn distillers grains increased
the proportion of unsaturated fatty acids in milk fat without changing milk
production.
PMID- 10194677
TI - Influence of particle size on the effectiveness of the fiber in corn silage.
AB - This experiment evaluated the influence of particle size on the effectiveness of
fiber in corn silage relative to that in hay crop, which consisted of mostly
alfalfa silage. Fifteen multiparous Holstein cows were assigned to five
treatments in each of 2 yr. The design was replicated but truncated 5 x 5 Latin
squares with three 21-d periods in 1994 and four 21-d periods in 1995. The five
diets (2-yr average, dry basis) were a basal, low fiber control with 12% neutral
detergent fiber (NDF) from hay crop forage (60% of total diet NDF); a high fiber
control with 22% NDF from hay crop forage (82% of total diet NDF); and three
diets each containing 12% NDF from hay crop forage and 9% NDF from coarse corn
silage, fine corn silage, or an equal mixture of the two. An increase in the
forage content above the basal amount with either hay crop or corn silage
increased rumination and total chewing time. No detectable differences in
rumination, total chewing time, or milk fat concentration were detected among the
corn silage diets. In yr 1, yield of milk components and dry matter intake were
greater for cows fed the four low alfalfa diets, but there was no effect due to
particle size of the corn silage. In yr 2, linear increases in milk, fat, and
protein yields were observed as the mean particle size of the corn silage
decreased. Reduction of corn silage particle size did not affect chewing
behavior.
PMID- 10194678
TI - Evaluation of the importance of the digestibility of neutral detergent fiber from
forage: effects on dry matter intake and milk yield of dairy cows.
AB - Effects of the digestibility of neutral detergent fiber (NDF) from forage on
performance of dairy cows were evaluated statistically using treatment means for
13 sets of forage comparisons reported in the literature. All comparisons
reported significant differences in NDF digestibilities of forages in situ or in
vitro. Treatment means were blocked by study or by additional factorial treatment
within a study to remove variation among experiments. The statistical model
included random effect of block, fixed factorial effect of NDF digestibility
(high or low), and dietary NDF concentration as a covariate. Enhanced NDF
digestibility of forage significantly increased dry matter intake (DMI) and milk
yield. A one-unit increase in NDF digestibility in vitro or in situ was
associated with a 0.17-kg increase in DMI and a 0.25-kg increase in 4% fat
corrected milk. Differences in NDF digestibility between treatments were greater
when measured in vitro or in situ than when measured in vivo. Digestibility of
NDF in vitro or in situ might be a better indicator of DMI than NDF digestibility
in vivo because forages with high in vitro or in situ NDF digestibilities might
have shorter rumen retention times, allowing greater DMI at the expense of NDF
digestibility in vivo. Digestibility of NDF is an important parameter of forage
quality.
PMID- 10194679
TI - Relationship of portal-drained viscera and liver net flux of glucose, lactate,
volatile fatty acids, and nitrogen metabolites to milk production in the ewe.
AB - The objectives of this study were, first, to determine the relationship between
hepatic glucose release and milk production and, second, to determine the
relationship between net hepatic uptake of gluconeogenic precursors and milk
production. Nine multiparous ewes were individually penned and fed an alfalfa hay
based diet for ad libitum intake. Catheters were surgically placed in the portal
vein, a branch of the hepatic vein, a mesenteric vein, and the abdominal aorta.
Metabolite fluxes across the portal-drained viscera and liver were subsequently
measured at 1, 3, 6, and 10 wk after parturition. Net hepatic glucose release,
net hepatic lactate uptake, and net hepatic propionate uptake increased with
increased milk production. Hepatic oxygen consumption increased with increased
net hepatic glucose release. Net hepatic glucose release increased with increased
hepatic propionate uptake and tended to increase with increases in metabolized
amino acid and lactate uptakes. The observed increases in oxygen consumption by
the portal-drained viscera with increased milk production were probably the
result of increased nutrient flux. Increased hepatic oxygen consumption with
increased milk production was probably due to increased glucose and urea
synthesis.
PMID- 10194680
TI - Dry matter intake and milk yield and composition of cows fed yeast prepartum and
postpartum.
AB - Thirty-six multiparous and 12 primiparous Holstein cows were utilized in a
completely randomized design to characterize the effects of feeding yeast
cultures (Saccharomyces cerevisiae) and enzymes on dry matter intake and milk
yield and composition. The prepartum diet consisted of a total mixed ration
containing chopped grass hay, corn silage, and grain pellet. The postpartum diet
consisted of a total mixed ration containing corn silage, legume silage, chopped
legume hay, and grain pellet. Treatments consisted of 1) whey control, 10 g/d; 2)
enzyme, 10 g/d; 3) yeast; 15 g/d; and 4) Biomate Yeast Plus (20 g/d; Chr. Hansen
BioSystems, Inc., Milwaukee, WI). Treatments were top-dressed at feeding time.
Cows were housed in a tie-stall barn, had continuous access to fresh water, and
were fed once daily at 0800 h for ad libitum intake. Daily intake and orts were
recorded beginning 28 d prior to the expected calving date through wk 13 of
lactation. Daily milk yield and weekly milk samples were collected through wk 13
of lactation. Body weight and body condition score were recorded once every 2 wk
throughout the experiment. Urine samples were collected at 30, 60, and 90 d of
lactation and were analyzed for allantoin and creatinine. Least squares means for
intake, milk yield, and milk composition were unaffected by treatment. The
allantoin to creatinine ratio was not affected by treatment. Yeast cultures with
or without enzyme had no direct effects on prepartum or postpartum dry matter
intake or milk yield and composition.
PMID- 10194681
TI - Effect of direct-fed fibrolytic enzymes on the lactational performance of dairy
cows.
AB - In trial 1, 30 midlactation (213 d in milk) Holstein cows were randomly assigned
to a control or enzyme treatment in a two-period crossover design and were fed a
total mixed ration based on alfalfa hay and silage. Cows on the enzyme treatment
received an enzyme solution containing cellulases and xylanases, which was
sprayed on the forage component of the ration at a rate of 1.65 ml/kg of forage
dry matter (DM) between 8 and 24 h prior to feeding. Cows consuming the forage
treated with enzyme produced more milk (27.2 vs. 25.9 kg/d) and digested more DM
per day than did cows fed the control forage. In trial 2, 40 early lactation
Holstein cows were assigned to one of four treatments for 16 wk. Following a 2-wk
covariate period, cows were assigned to 1) no enzyme treatment, 2) a low (1.25
ml/kg of forage DM) enzyme treatment, 3) a medium (2.5 ml/kg of forage DM) enzyme
treatment, or 4) a high (5.0 ml/kg of forage DM) enzyme treatment. Enzymes were a
2:1 combination of cellulase and xylanase diluted in water and sprayed on a
combination of alfalfa hay and silage and whole cottonseed immediately before
mixing with a concentrate based on barley. Dry matter intakes were similar for
cows on treatments 2, 3, and 4 and were greater than those for cows on treatment
1. Production of milk, 3.5% fat-corrected milk, and energy-corrected milk was
greater for cows on treatment 3 than for cows on treatment 1. Fibrolytic enzymes
applied to the forage portion of the rations prior to feeding improved
lactational performance of early and midlactation cows.
PMID- 10194682
TI - True absorption of calcium and phosphorus from corn silage fed to nonlactating,
pregnant dairy cows.
AB - A crossover design was implemented using four nonlactating dairy cows [mean body
weight (BW) = 678 kg] and two rations to measure the true absorption of Ca and P
from corn silage. True absorption was calculated after dosing cows intravenously
with 45Ca and 32P to measure endogenous fecal losses. Rations consisted mainly of
corn silage and were formulated to supply 32 g/d of Ca and 20 g/d of P or 16 g/d
of Ca and 12 g/d of P. The percentages of total Ca and P that came from corn
silage were 95 and 77%, respectively, for ration 1, and 98 and 79%, respectively,
for ration 2. Cows ate more dry matter (10.9 vs. 10.2 kg/d) when consuming the
corn silage in ration 1 than when consuming the corn silage in ration 2. Calcium
intake was greater for cows fed ration 1 than for cows fed ration 2 (32.6 vs.
16.1 g/d), and P intake was greater for cows fed ration 1 than for cows fed
ration 2 (20.1 vs. 11.7 g/d). True absorption of Ca was 34.4 and 43.7% for
rations 1 and 2, respectively, and true absorption of P was 84.5 and 93.9% for
rations 1 and 2, respectively. True absorption of Ca was about equal to values
currently used in the National Research Council (NRC) feeding standards, but true
absorption of P was higher than values currently used by the NRC. Fecal
endogenous excretion of Ca (mean = 8.23 mg/kg of BW per d) was one-half of the
value currently used by the NRC, and fecal endogenous excretion of P (mean = 7.23
mg/kg of BW per d) was only slightly less than NRC values.
PMID- 10194683
TI - Effect of administration of vitamin E and selenium during the dry period on
mammary health and milk cell counts in dairy ewes.
AB - The effect of parenteral administration of two subcutaneous injections of vitamin
E and Se (5 mg and 0.1 mg/kg of body weight, respectively) during the dry period
on the mammary health and milk somatic cell counts of 25 dairy ewes was
investigated. Supplementation reduced somatic cell counts (5.4 vs. 6.0 log10)
during the subsequent lactation but had no effect on the incidence of clinical
mastitis (4% vs. 6%) and intramammary infections (9.0% vs. 11.3%). Furthermore,
the administration of vitamin E and Se was associated with differences in
differential cell counts of milk samples (macrophages, 48.8% vs. 38.4%;
polymorphonuclear neutrophils, 40.1% vs. 50.7%; and eosinophils, 0.7% vs. 1.4%
for control ewes and ewes receiving supplements, respectively). The
administration of these supplements also increased erythrocyte glutathione
peroxidase activity (139.5 vs. 86.3 U/ml of packed cell volume) and the
percentage of blood neutrophils that reduced nitroblue tetrazolium after
bacterial extract stimulation (48.6% vs. 38.7%). Parenteral administration of
vitamin E and Se to ewes during the dry period appeared to have influenced
mammary gland status during the subsequent lactation and particularly total and
differential milk cell counts.
PMID- 10194684
TI - Genetic and environmental smoothing of lactation curves with cubic splines.
AB - Most approaches to modeling lactation curves involve parametric curves with fixed
or random coefficients. In either case, the resulting models require the
specification on an underlying parametric curve. The fitting of splines
represents a semiparametric approach to the problem. In the context of animal
breeding, cubic smoothing splines are particularly convenient because they can be
incorporated into a suitably constructed mixed model. The potential for the use
of splines in modeling lactation curves is explored with a simple example, and
the results are compared with those using a random regression model. The spline
model provides greater flexibility at the cost of additional computation. Splines
are shown to be capable of picking up features of the lactation curve that are
missed by the random regression model.
PMID- 10194685
TI - Genetic parameters of lactation cell counts and milk and protein yields in dairy
ewes.
AB - A total of 3231 lactation records of somatic cell counts (SCC), milk yield, and
protein percentage for 2379 Spanish Churra ewes from 10 flocks were used to
estimate genetic and environmental parameters. Genetic parameters were estimated
by REML with a multitrait repeatability animal model. A lactation measure of SCC
was obtained as the mean of test day log SCC adjusted for stage of lactation.
Heritabilities for SCC, milk yield, and protein percentage were 0.12, 0.24, and
0.17, respectively. The corresponding repeatabilities were 0.35, 0.49, and 0.38.
Heritability and repeatability estimates of SCC obtained from this study fell
within the range frequently reported for dairy cows. Therefore, as practiced for
dairy cattle, future possibilities for sire evaluation to improve udder health
status using lactation measures of SCC for dairy sheep are not rejected, although
hygienic practices are regarded as more important. Genetic correlations of SCC
with milk yield and protein percentage were -0.15 and -0.03, respectively. The
genetic correlation between milk yield and protein percentage was -0.47. The low
genetic correlations of SCC with milk yield and protein percentage may indicate
that breeding decisions to improve milk and protein yields of Churra ewes are not
expected to have an effective correlated response in SCC.
PMID- 10194686
TI - Efficacy of parenterally or intramammarily administered tilmicosin or ceftiofur
against Staphylococcus aureus mastitis during lactation.
AB - Two antibiotic preparations, tilmicosin and ceftiofur, were tested intramammarily
and parenterally against Staphylococcus aureus mastitis in lactating cows.
Neither product was effective as a lactating cow treatment at the doses and
durations of treatment tested. Injection or infusion of tilmicosin and infusion
of ceftiofur resulted in reductions of bacteria present in milk; however, only
one quarter treated with infusion of tilmicosin was cured, and no cures were
observed for the other treatments. Somatic cell counts were transiently reduced
by infusion of ceftiofur and by infusion and injection of tilmicosin; however,
they returned to pretreatment values by 28 d posttreatment.
PMID- 10194687
TI - Review of investigations regarding the etiology of port site tumor recurrence.
AB - The animal and human studies presented, at first glance, present a confusing and
conflicting story. In regards to the animal studies, much of this confusion can
be traced to the use of a variety of different models, none of which truly
reproduces the human situation. Nonetheless, there is much to be gleaned from
these efforts. The authors present conceptualization of the port wound tumor
dilemma follows. In order for wound tumors to develop, viable tumor cells must be
liberated from the primary tumor and find transport to a wound. Rarely, patients
with colon tumors will present with or will develop widespread intraabdominal
carcinomatosis. These tumors have the ability to spontaneously shed considerable
numbers of viable cells which have the ability to implant on uninjured peritoneal
surfaces. Unfortunately, the surgeon has little chance for success in these
patients with either open or minimally invasive methods. Fortunately, most colon
adenocarcinomas do not spread in this manner. Differences in the clinical
behavior and manifestations of colon tumors most likely reflect the genetic
makeup of individual tumors. Colonic neoplasm's ability to invade and metastasize
varies considerably from tumor to tumor. Thankfully, as mentioned, the vast
majority of colon tumors are not prone to cause carcinomatosis. Despite this
fact, the human data available suggests that tumor cells can be found in the
peritoneal cavity using sophisticated methods in about half of the patients after
colectomy. If this is the case, then why aren't more wound tumors seen? Logic
dictates that there must be a critical number of free intraabdominal cells above
which successful wound seeding is likely. It makes sense that traumatization of
the tumor will result in increased numbers of liberated cells. Therefore,
surgical approach and technique should impact considerably on outcome. For the
majority of colon tumors, if the lesion is assiduously avoided during
mobilization and resection, it is unlikely that enough tumor cells will be shed
to result in port site tumors. The recent interim results of the Cleveland
Clinic's and the Barcelona randomized trials certainly support such a hypothesis.
With over 300 patients enrolled (combined series) and with an average follow up
of over 2 years, in neither trial has a port site tumor been noted. Similarly,
with an average follow up of just under 3 years, Franklin et al noted that there
were no port site tumors in their prospective trial of 191 consecutive
laparoscopic colectomies for cancer. In the clinical setting, experience and
surgical expertise seem to be the best predictor of outcome, in regards to wound
tumors. The few animal studies that allow assessment of the impact of technique
(i.e. those that utilize an intraabdominal solid tumor model which allows tumor
excision) indeed support this hypothesis. In these studies poor technique
resulted in significantly more wound tumors. Furthermore, it has been shown that
for laparoscopic procedures, there is a definite learning period during which the
incidence of wound tumors is considerably higher than that of open resection.
With experience the laparoscopic incidence falls to that of open resection.
Furthermore, a number of recent studies suggest that is possible to lower the
incidence of wound tumors via peritoneal and wound irrigation with a variety of
agents. These animal study results are in keeping with the recent clinical
results. Both would suggest that given proper and adequate training and with
sufficient attention being paid to avoid tumor handling that the incidence of
wound tumors will be as low as that following open colectomy. How large a part,
if any, does the CO2 pneumoperitoneum play in the port wound tumor story?
Certainly, the results of the bulk of the animal studies performed, to date, have
suggested that the CO2 pneumoperitoneum plays a critical role in the development
of port wound tumors. With few exceptions, these studies have utilized tumor cel
PMID- 10194688
TI - Routine laparoscopic cholangiography: a means of avoiding unnecessary endoscopic
retrograde cholangiopancreatography.
AB - Controversy exists between routine and selective on-table cholangiography during
laparoscopic cholecystectomy. Endoscopic retrograde cholangiopancreatography
(ERCP) has been suggested as first-line investigation in patients with suspected
duct stones. We report a series of 154 on-table cholangiograms (OTC) and consider
the requirements for ERCP according to historical and biochemical markers. A
retrospective review of 154 consecutive patients undergoing laparoscopic
cholecystectomy with OTC was performed. Historical and biochemical markers of
duct stones were examined with respect to the necessity of ERCP. OTC was
performed, with a 100% success rate, and took approximately 10 min. Eight (5.2%)
of the patients had duct stones. Only one did not have preoperative indicators of
duct stones. Sixty-six patients had preoperative markers suggesting the need for
ERCP. According to the OTC findings, 59 (89.4%) of these patients would have
undergone unnecessary ERCP. Routine laparoscopic OTC is advocated because it
maintains expertise in the technique and avoids unnecessary ERCP with its
attendant costs and complications.
PMID- 10194689
TI - Laparoscopic gastric banding for morbid obesity.
AB - Morbid obesity is a serious disease that is responsible for several comorbid
conditions. Body mass indices > 40 require surgical procedures if diet programs
fail. Laparoscopic adjustable gastric banding (LAGB), a more recently introduced
gastric restrictive procedure, was designed to be a minimally invasive and
reversible operation. 184 patients (164 women, 20 men) with a mean body mass
index of 47.8 kg/m2 (range 36-79) were operated on. All patients had been
excessively overweight for > 5 years. Each patient was given general anesthesia,
and an adjustable LAP-BAND was implanted laparoscopically. The pouch size was 15
ml in all cases; and 3-4 sutures were placed to prevent dislocation. The
conversion rate was 0%. The median operating time was 65 min (range 45-190). The
mortality was 0%. The mean hospital stay was 5 days (range 4-6). The mean excess
weight loss was 16% in 4 weeks, 23% in 3 months, 31% in 6 months, 58% in 1 year,
and 87% in 2 years. The patient satisfaction index was 97.6%. Once a surgeon has
acquired the necessary laparoscopic surgical experience, LAGB is a feasible,
safe, and simple procedure with excellent postoperative results. LAGB does not
permanently modify the anatomy of the stomach and maintains the natural
continuity of the alimentary tract, while at the same time ensuring a steady
weight reduction in morbidly obese patients. The fact that the gastric band can
be applied laparoscopically is a significant advantage in this group of high-risk
patients, who have less pain, faster postoperative recovery, more rapid return to
normal activities, fewer wound infections, fewer hernia problems, and better
cosmetic results. The rate of postoperative complications is approximately 9%. In
1.1% of patients, erosion occurred, and in 2.2%, slippage of the band. The rate
of port-related complications was 3.2%. Reoperations were necessary in 6.4% of
the patients.
PMID- 10194690
TI - Timing of endoscopic retrograde cholangiopancreatography and laparoscopic
cholecystectomy in the treatment of choledocholithiasis.
AB - Although experience with laparoscopic approaches to common duct stones is
increasing, endoscopic retrograde cholangiopancreatography (ERCP) performed
either before or after laparoscopic cholecystectomy (LC) remains the most common
approach. Debate remains as to the best timing for ERCP in patients with
suspected choledocholithiasis. Because clinical, laboratory, and radiological
data are poor predictors of choledocholithiasis, many ERCPs done before LC give
negative results. ERCP performed after LC with a positive intraoperative
cholangiogram (i.o.p.) would eliminate many unnecessary preoperative endoscopic
studies. This is a retrospective analysis of the treatment of choledocholithiasis
with the combination of LC and ERCP. All patients included could have had ERCP
preoperatively or postoperatively; therefore, those with cholangitis requiring
emergent preoperative ERCP were excluded. Two groups of patients were compared:
those who underwent ERCP followed by LC and those who underwent LC and IOC
followed by ERCP. No significant differences were found with respect to age,
gender, health status, clinical presentation, laboratory values (most liver
functions, white blood cell count, hemoglobin, and serum amylase), surgery time,
blood loss, ERCP time, time between treatment modalities, and days to regular
diet. However, the preoperative ERCP group was found to have a longer hospital
stay (6.7 days vs. 3.5 days, p = 0.003) and higher hospital cost ($9,406.39 vs.
$12,816.23, p = 0.05). The preoperative ERCP group had two patients requiring two
ERCPs to clear the common duct, one patient requiring conversion to open
procedure because of failed LC, and four minor complications. The postoperative
ERCP group had no failed LC, IOC, or postoperative ERCPs and one minor
complication. The rate of false positive IOC was 6.7% and of negative
preoperative ERCP, 43%. We conclude that in the absence of cholangitis requiring
emergent endoscopic decompression, suspected choledocholithiasis can be
successfully managed first with LC, ERCP being reserved for patients with a
positive IOC. This eliminates many negative preoperative ERCPs.
PMID- 10194691
TI - Laparoscopy in the context of lower abdominal pain in young women.
AB - The management of lower abdominal pain in young women carries up to 45% chance of
diagnostic error. Laparoscopic management may be particularly beneficial in this
subset of patients. This study reviews the authors' experience with laparoscopy
as a potential diagnostic and therapeutic tool in young women with lower
abdominal pain. The authors analyzed 121 consecutive female patients, with a mean
age of 30 years, who were evaluated from June 1995 to October 1997. All patients
were managed by early laparoscopy within 24 h from the onset of symptoms.
Radiographic imaging, including computed tomography and ultrasound, was performed
in 79 patients (65.2%). Laparoscopy was diagnostic in all cases. In 58 patients
(48%), multiple pathologic conditions were identified. Acute appendicitis was the
most common diagnosis (82.6%), and benign gynecologic disorders was the
predominant reason for multiple pathologic conditions (clinical evaluation was
erroneous in 15% of patients). In 96% of patients, definite surgical treatment
was provided laparoscopically. The mean hospitalization time was 2.0 +/- 1 days,
and the mean operative time was 59.8 +/- 21 min. The overall complication rate
was 2.5%. In young women, early laparoscopy can offer a safe and effective
alternative for the definite diagnosis and treatment of lower abdominal pain.
PMID- 10194692
TI - Pubic bone suburethral stabilization sling: laparoscopic assessment of a
transvaginal operation for the treatment of stress urinary incontinence.
AB - The objective was to examine laparoscopically the mechanism and precision of a
new transvaginal method for fixation of a suburethral stabilization sling
prosthesis designed for the treatment of recurrent stress urinary incontinence.
Nine patients with recurrent stress urinary incontinence after previous anti
incontinence surgery underwent transvaginal placement of a pretrimmed 2.0 x 5.5
cm synthetic pubic bone suburethral stabilization sling prosthesis with pubic
bone anchors. Before the sling fixation sutures were tied, the space of Retzius
was opened laparoscopically with an operative laparoscope, and sling placement
was assessed. Patients were followed up postoperatively at routine intervals. All
nine procedures were accomplished uneventfully and as planned. Laparoscopic
surveillance demonstrated that bone anchor placement by palpation was accurate
and that low-tension sling fixation necessitated 2.0- to 2.5-cm suture bridges
between the lateral sling edges and the pubic bone anchors in all cases.
Continence was restored in all cases; two patients experienced mild, transient
urinary retention; one patient experienced transient detrusor instability. No
significant postoperative complications were noted. Low-tension pubic bone
suburethral sling placement requires suture bridging of approximately 2.0 to 2.5
cm per side when a prosthesis 5.5 cm long is employed.
PMID- 10194693
TI - Nausea and vomiting after laparoscopic gynecological surgery: a study of the
incidence and the effects of tropisetron prophylaxis.
AB - The authors studied the incidence of postoperative nausea and vomiting (PONV) and
the effect of prophylactic tropisetron, a 5-HT3 antagonist, during the first 24 h
following elective gynecologic laparoscopic surgery. Thirty-two of 68 (47%) of
the patients experienced nausea or vomiting some time during the observation
period. Sixteen of the 32 PONV patients (50%) had their first emetic symptoms
after discharge from the recovery room. We could see no difference in the
frequency of PONV in the patients who were given prophylactic tropisetron 5 mg
orally before anesthesia.
PMID- 10194694
TI - Combined use of mini-laparoscope and conventional laparoscope in laparoscopic
cholecystectomy: preservation of minimal invasiveness.
AB - Mini-laparoscopic cholecystectomy using a 2-mm mini-laparoscope has been reported
to be beneficial but technically difficult. This study attempted to evaluate the
relative efficacy of a new method, which provides the benefits of both
conventional and mini-laparoscopic cholecystectomy. From March 1997 to December
1997, 143 patients (49 men, 94 women, mean age 52.6 years, range 20-79), American
Society of Anesthesiology (ASA) class I-II, underwent elective cholecystectomy by
a combination of a 2-mm mini-laparoscope and 10-mm conventional laparoscope
(combined lap-aroscopic cholecystectomy, C group) in National Taiwan University
Hospital, Taipei, Taiwan. The entire procedure was done through four ports (one
11-mm port and three 2-mm ports). For comparison, records from 46 patients
receiving mini-laparoscopic cholecystectomy (M group, 17 men, 29 women, mean age
49.0 years, range 26-76) and 139 patients receiving conventional laparoscopic
cholecystectomy (L group, 47 men, 92 women, mean age 51.2 years, range 28-82) by
the same operative team were included retrospectively. Mean operation time, time
until first postoperative oral intake, dosage of analgesic, and postoperative
hospital stay as well as possible complications were compared. No significant
differences concerning the age, sex, and ASA classification were identified
between all groups. The operative time of the C group (59.9 +/- 17.3 min, p =
0.420) but was significantly shorter than that of the M group (72.8 +/- 26.5 min,
p < 0.001). No differences concerning the analgesic usage (0.5 +/- 0.8 unit vs.
0.4 +/- 0.7 unit, p = 0.372), postoperative oral intake (4.4 +/- 1.9 h vs. 3.3 +/
2.3 h, p = 0.067), and postoperative hospital stay (1.7 +/- 0.7 days vs. 1.7 +/-
0.7 days, p = 0.941) were found between the C group and the M group. However,
compared with the L group, analgesic usage (0.5 +/- 0.8 unit vs. 0.8 +/- 1.0
unit, p = 0.003) and time until first postoperative oral intake (4.4 +/- 1.9 h
vs. 6.2 +/- 3.0 h, p < 0.001) were less, and the postoperative hospital stay (1.7
+/- 0.7 days vs. 2.0 +/- 0.9 days, p = 0.002) was significantly shorter in the C
group. Combined use of the mini-laparoscope and the conventional laparoscope in
cholecystectomy provides the benefits of both conventional laparoscopic and mini
laparoscopic cholecystectomy. It is easier to perform than cholecystectomy that
uses the mini-laparoscope alone and results in a much smaller wound with less
pain than conventional laparoscopic cholecystectomy. It is a feasible, safe
procedure, and the minimal invasiveness of mini-laparoscopic cholecystectomy is
preserved. It is an alternative way to deal with gallstone disease, especially
for younger women, who tend to be more concerned about cosmetic outcome.
PMID- 10194695
TI - Laparoscopic ultrasound guidance for laparoscopic resection of benign gastric
tumors.
AB - Laparoscopic excision of gastric leiomyoma is technically feasible and safe, but
it may fail to localize the exact placement of the lesion because of the lack of
tactile sensitivity. The authors present two cases of small gastric leiomyomas
that were resected by a totally laparoscopic approach, assisted with
intraoperative laparoscopic ultrasonography because the lesions could not be
palpated. A gastric wedge resection with tumor-free margins was performed with an
endostapler device. Use of a harmonic scalpel to divide the gastroepiploic
vessels facilitated the laparoscopic procedure.
PMID- 10194696
TI - Single-stage laparoscopic and endoscopic treatment for choledocholithiasis: a
novel approach.
AB - The transcystic approach is ideal for the management of choledocholithiasis
detected during the course of laparoscopic cholecystectomy. When this approach is
not possible or fails, current alternatives include laparoscopic choledochotomy,
conversion to open common bile duct exploration, or postoperative endoscopic
sphincterotomy (ES). Intraoperative ES is not routinely advised, as it is thought
to be difficult to carry out in the operating room with the patient in the supine
position. We challenged this concept and have performed ES intraoperatively when
the transcystic approach had failed. Five consecutive patients in whom
transcystic extraction of choledocholiths had failed underwent intraoperative ES.
The laparoscopic procedure was terminated, the trocars were removed, the wounds
were closed, and the patients were placed in the left lateral decubitus position.
In this position, the endoscope was inserted, ES was performed under fluoroscopic
guidance, and choledocholithiasis was treated. There were no difficulties or
complications, and the postoperative course was similar to that of a simple
laparoscopic cholecystectomy in all five patients. Intraoperative ES is a viable
and effective treatment for choledocholithiasis when the transcystic approach
fails. This novel approach to choledocholithiasis is well tolerated and may save
the extra time and effort associated with all other current alternatives.
PMID- 10194697
TI - Routine use of open laparoscopy: 1,006 consecutive cases.
AB - Blind insertion of the Veress needle and of the first trocar is a significant
cause of laparoscopic surgery complications. Despite this risk, the closed
technique is still more popular than the open one. The authors retrospectively
evaluated 1006 consecutive laparoscopic operations in which Hasson's technique
was routinely performed. The overall complication rate was 2.2%, but the vast
majority of complications occurred during the first 50 cases (6% vs. 1.9%). They
conclude that after a learning phase of about 50 cases, Hasson's technique is a
quick and safe procedure.
PMID- 10194698
TI - A simple and inexpensive technique for closing trocar sites and grasping sutures.
AB - Grasping sutures during laparoscopic surgery is useful in closing trocar sites,
repairing ventral hernias, and securing abdominal wall bleeding. This can be a
cumbersome task through small incisions. An 18 gauge spinal needle and the suture
of choice for accomplishing the job at hand can be used with a laparoscopic
assisted technique that is simple, inexpensive, and easy to learn. Surgeons
performing laparoscopy should add this technique to their repertoire.
PMID- 10194699
TI - Laparoscopic resection of gastric diverticulum.
AB - Gastric diverticulum is a rare disorder. The laparoscopic approach may be ideal
for the resection of gastric diverticulum in some cases. The authors believe this
to be the first reported case of gastric diverticulum resected laparoscopically.
A 59-year-old woman was admitted with indigestion and epigastric pain. Upper
gastrointestinal series showed a single diverticulum (3 x 2 cm) on the posterior
wall of the upper part of the stomach. The neck of the diverticulum was
relatively narrow. Gastroduodenoscopy revealed that food residues were impacted
within the diverticular pouch. Other areas of the stomach and the duodenum were
normal. Abdominal ultrasonography showed no other pathologic conditions in the
upper part of abdomen. On operation, the lesser sac was entered by division of
the greater omentum along the avascular plane of the transverse colonic
attachment. The location of the diverticulum was confirmed by intraoperative
gastroscopy. Using a 5-cannula techniques, the diverticulum was resected with an
endoscopic linear stapler device. Pathologic examination of the resected specimen
demonstrated chronic superficial gastritis. Flatus was passed out on the first
postoperative day, diet was started from the second day, and the patient was
discharged on the fifth day without problems.
PMID- 10194700
TI - Laparoscopic repair of a Morgagni hernia: report of a case and review of the
literature.
AB - A case is reported of an 85-year-old woman with subacute intestinal obstruction
due to a large Morgagni hernia containing the transverse colon. The repair was
carried out laparoscopically without a mesh. The procedure lasted 45 min, and the
patient was discharged after 4 days. According to the literature, mini-invasive
repair of a Morgagni hernia can be performed easily and without complications. In
only few cases was a mesh necessary. The Morgagni hernia must be considered a
clear indication for laparoscopic surgery, which should be offered as the first
approach to this disease.
PMID- 10194701
TI - Laparoscopic Roux-en-Y gastric bypass: a case report at one-year follow-up.
AB - Surgery is the only treatment for morbid obesity that has been proven to achieve
a significant long-term weight loss. The Roux-en-Y gastric bypass procedure has
been performed for the treatment of morbid obesity over the past two decades with
excellent results. Wound complications and perioperative morbidity remain
unresolved problems of the procedure. A laparoscopic approach to this procedure
has great potential to minimize the complications of this highly effective
technique. We describe a laparoscopically performed Roux-en-Y gastric bypass in a
28-year-old woman with morbid obesity. The technique described here preserves the
anatomic construct of the operation but introduces the benefit of the
laparoscopic approach.
PMID- 10194702
TI - Full robotic assistance for laparoscopic tubal anastomosis: a case report.
AB - Optical magnification and long instrumentation significantly increase surgical
tremor, which makes laparoscopic microsuturing difficult. Therefore, laparoscopic
tubal anastomosis has not gained wide acceptance among gynecologic surgeons.
Robotic assistance facilitates this type of procedure by filtering tremor,
reducing the surgeon's fatigue, and scaling the maneuvers. The authors have
successfully completed a case of laparoscopic tubal reanastomosis using a "master
slave" robot to perform the standard microsuturing technique. A 33-year-old
woman, gravida 2, para 2, requested reversal of her previous tubal ligature. A
right isthmic-isthmic tubal anastomosis was performed laparoscopically, with
faithful adherence to the authors' standard technique applied at laparotomy. Full
robotic assistance was used to anastomose the tube. A chromotubation test showed
anastomotic patency without leak. The patient recovered uneventfully after
surgery and was discharged within 24 h after the procedure. Laparoscopic
microsurgical tubal anastomosis with full robotic assistance is feasible and safe
in humans.
PMID- 10194703
TI - High-level disinfection with 2% alkalinized glutaraldehyde solution for reuse of
laparoscopic disposable plastic trocars.
PMID- 10194704
TI - MRI of liver metastases: limitation of spleen-liver model in optimizing pulse
sequences.
AB - The spleen-liver model, as a predictor for contrast-to-noise ratio (C/N) in liver
metastases, was verified for seven sequences in 22 patients with 70 colorectal
metastases. Optimization of conventional spin-echo, T1-magnetization-prepared
gradient-echo and fat frequency-selective presaturation inversion-recovery fast
spin echo can be done using the spleen-liver model. C/N of liver-spleen and liver
metastases, however, differed significantly on our T1 gradient-echo and T2
weighted fast spin-echo images, with and without fat-selective saturation.
PMID- 10194705
TI - Pelvic floor descent in females: comparative study of colpocystodefecography and
dynamic fast MR imaging.
AB - The purpose of this study was to compare fast dynamic magnetic resonance imaging
(MRI) with colpocystodefecography (CCD) in the evaluation of pelvic floor descent
in women. Thirty-five women with clinical evidence of pelvic floor descent were
studied. A fast single-shot MR sequence was performed in the supine position
during pelvic floor relaxation and during maximal pelvic strain. On the same day,
a dynamic CCD was performed with the patient seated on a stool-chair. The degree
of descent of the bladder, vagina, and anorectal junction was evaluated as the
vertical distance between the pubococcygeal line and the bladder base, the
vaginal vault, and the anorectal junction, respectively. A bulge of more than 3
cm measured as the distance between the extended line of the anterior border of
the anal canal and the tip of the rectocele was interpreted as a rectocele. MRI
was compared with CCD during maximal pelvic strain (CCD 1) and during voiding and
defecation (CCD II). CCD was considered as the gold standard. Compared with
clinical examination, CCD I showed a larger number of involved compartments,
except for the middle compartment. CCD II was superior to clinical examination in
all cases. In comparison with CCD I and especially CCD II, MRI had a lower
sensitivity, especially for the anterior and middle compartment. Even four
enteroceles seen on CCD II were not detected by MRI. When CCD I and CCD II were
compared, a cystocele, a vaginal vault prolapse, an enterocele, and a rectocele
were more readily seen on CCD II than with CCD I. When compared with CCD, supine
dynamic MRI is unreliable, especially in the anterior and middle compartment.
Even in the detection of enteroceles CCD was superior to MRI. In general, the
best results with MRI can be expected for evaluation of the rectum.
PMID- 10194706
TI - Pelvic floor descent: dynamic MR imaging using a half-Fourier RARE sequence.
AB - Dynamic magnetic resonance imaging (MRI) using a single shot fast spin-echo
technique was evaluated as a noninvasive alternative to cystourethography or
colpocystorectography in patients with pelvic organ prolapse and/or urinary
incontinence. Thirty-two patients were included in this prospective study.
Colpocystorectography was performed in 10 patients who previously had undergone
hysterectomy and in 2 patients without history of hysterectomy with clinical
suspicion of rectoceles. Bead-chain cystourethrography was performed in 20
patients without hysterectomy. For dynamic MRI, a single-slice half-Fourier RARE
sequence (imaging time 2 seconds) was used to depict the pelvic organs at
different levels of pelvic strain. The results obtained with dynamic MRI were
correlated with the x-ray findings. All 17 cystoceles, 10 rectoceles, 2
enteroceles, and 7 vaginal prolapses could be demonstrated on MRI. Diagnostic
information gained from these images was equivalent to that obtained with
colpocystorectography and superior to that obtained with cystourethrography; with
the latter, important findings were missed (four rectoceles). We conclude that
dynamic MRI of the pelvic floor with a half-Fourier RARE sequence can reliably
detect descents of all three pelvic compartments, that it requires no contrast
agent, and that no radiation exposure is involved.
PMID- 10194707
TI - T2-weighted MRI of the uterus: fast spin echo vs. breath-hold fast spin echo.
AB - This study compared one routine T2-weighted fast spin echo (T2FSE) sequence with
a breath-hold T2FSE (BH T2FSE) sequence of the female pelvis for image quality,
uterine anatomy, lesion detection, and signal intensity measurements. Thirty-two
consecutive women (mean age 41.7 years) were imaged at 1.5 T with one high
resolution routine T2FSE sequence and one BH T2FSE sequence in the sagittal plane
as part of comprehensive pelvic magnetic resonance imaging. The different image
sets were rated separately for imaging characteristics (overall image quality,
uterine anatomy definition, lesion detection, and free fluid conspicuity) and
then compared side by side. The image sets were also compared for artifacts
(ghosting, blurring, pulsatility, and chemical shift misregistration). Signal-to
noise (S/N) and signal difference-to-noise (SD/N) ratios were calculated for the
different uterine zones, uterine abnormalities, free fluid, rectus abdominis
muscle, and bladder. Contrast-to-noise ratios (CNRs) were calculated for uterine
abnormalities. Twenty-eight uterine abnormalities were detected in 20 patients
and included leiomyomata (13 patients), adenomyosis (7 patients), benign
endometrial polyps (6 patients), endometrial carcinoma (1 patient), and pregnancy
(1 patient). BH T2FSE was superior or equivalent to T2FSE for overall image
quality in 23/32 patients (71.8%), uterine anatomy definition in 19/32 patients
(59.3%), and lesion detection in 13/20 patients (65%). BH T2FSE performed less
well than T2FSE for free fluid conspicuity in 5/5 (100%) patients. BH T2FSE was
equivalent to or less affected than T2FSE for ghosting artifact in 24/32 patients
(75%) and blurring artifact in 29/32 patients (90.6%). Pulsatility and chemical
shift artifacts were not problematic for either image set. S/N and SD/N were
higher for all BH T2FSE determinations compared with T2FSE. For the endometrium,
junctional zone, myometrium, and bladder, these differences were statistically
significant. There were no statistically significant differences for CNR between
the two image sets, although BH T2FSE values for leiomyomata, adenomyosis, and
abnormal endometria were higher than those calculated for T2FSE. All pathology
detected with T2FSE was detected on BH T2FSE despite the breath-hold sequence's
inherently poorer spatial resolution compared with the non-breath-hold sequence.
BH T2FSE may be able to replace T2FSE for some uterine applications with a
substantial time savings.
PMID- 10194708
TI - Detection of residual quadrupolar interaction in the human breast in vivo using
sodium-23 multiple quantum spectroscopy.
AB - Sodium multiple quantum (MQ) spectroscopy of the human breast in vivo was
performed. Double quantum (DQ) filtered spectra were used to demonstrate the
existence of a non-vanishing (residual) quadrupolar interaction in the tissue.
Triple quantum (TQ) filtered spectra were used to measure the two time constants
associated with the biexponential transverse relaxation times of sodium in
biological tissues. The two time constants were found to be 0.64 and 26.57 msec.
The potential applications of this finding are discussed.
PMID- 10194709
TI - Automated monitoring of diaphragm end-expiratory position for real-time navigator
echo MR coronary angiography.
AB - Real-time navigator echo (NE)-gated magnetic resonance coronary angiography
(MRCA) during free respiration is now possible. However, the mean diaphragm end
expiratory position (DEEP) drifts over time, and this results in a reduction in
scanning efficiency and increased artifacts due to the acquisition of data during
periods of high diaphragm velocity. To address these problems, a diaphragm
monitoring program that follows the mean DEEP over time has been developed.
Fifteen subjects with ischemic heart disease underwent continuous NE monitoring
of their diaphragm for 30 minutes. Using these diaphragm traces, theoretical MRCA
scans were performed. Several diaphragm monitoring algorithms were developed and
compared with the simplest case (a stationary 5 mm NE acceptance window placed
around the mean DEEP, as measured by NE monitoring at the outset of the scan). An
overall scan efficiency was calculated, and the number of completed scans where
the mean DEEP lay within the NE acceptance window was recorded. Of the six
algorithms considered, the most effective one monitored the mean DEEP and
prospectively placed the upper limit of the NE acceptance window on this position
for the subsequent acquisition. Using this algorithm in comparison with the
simplest stationary scenario, both scan efficiency (47.9% vs. 38.5%, P = 0.01)
and the number of completed scans where the mean DEEP lay within the NE
acceptance window (71.2 vs. 30.3, P < 0.001) were improved. The implementation of
such a monitoring algorithm, in combination with adaptive motion correction
techniques, should improve overall scan efficiency while maintaining the end
expiratory position at the top end of the NE acceptance window, to reduce image
artifacts.
PMID- 10194710
TI - Use of the mean transit time of an intravascular contrast agent as an exchange
insensitive index of myocardial perfusion.
AB - A simple two-compartment model was used to study the effects of water exchange on
the signal produced by an inversion recovery prepared rapid gradient-echo
sequence during the first passage of a low dose of an intravascular contrast
agent. Water exchange at intermediate rates of exchange (1-10 Hz) between the
vascular and extravascular spaces caused the form of the signal changes during
the first pass to be dependent on both the fractional sizes of the vascular and
extravascular compartments and on the exchange rate. Unless the effects of
exchange are minimized by using a very short inversion time, parameters such as
the peak height and area under the curve will be affected by regional and/or
pathological variations in the exchange rate and the size of the vascular
fraction. The mean transit time (MTT) is, however, less affected by water
exchange. Experimental first-pass data produced by intravascular low-dose
injections of iron oxide particles were studied in five pigs at 0.5 T. The MTT as
derived from the first-pass curves, without deconvolution with the arterial input
function, was well correlated with the myocardial blood flow (MBF) as measured
using radioactive microspheres (r = 0.70, n = 52, P < 0.01). Other first-pass
parameters such as the peak height or area under the curve exhibited either a
poorer, or no, correlation with the MBF. The data suggest that the MTT of the
first pass of an intravascular contrast agent may be a robust, quantitative
method for assessing myocardial blood flow in patients.
PMID- 10194711
TI - Simultaneous MRI tagging and through-plane velocity quantification: a three
dimensional myocardial motion tracking algorithm.
AB - A tracking algorithm was developed for calculation of three-dimensional point
specific myocardial motion. The algorithm was designed for images acquired with
simultaneous magnetic resonance imaging (MRI) grid tagging and through-plane
velocity quantification. The tagging grid provided the in-plane motion while the
velocity quantification measured the through-plane motion. In four healthy
volunteers, the in vivo performance was evaluated by comparing the systolic
through-plane displacement with the displacement of tagging-grid intersections in
long-axis images. The correlation coefficient was 0.93 (P < 0.001, N = 183). A t
test for paired samples revealed a small underestimation of the through-plane
displacement by 0.04 +/- 0.09 cm (mean +/- SD, P < 0.001) on an average
displacement of 0.77 +/- 0.23 cm toward the apex. The authors conclude that three
dimensional point-specific motion tracking based on simultaneous tagging and
velocity quantification is competitive with other methods such as tagging in
mutually orthogonal image planes or quantification of three orthogonal velocity
components.
PMID- 10194712
TI - Dynamic MR imaging of the carotid wall.
AB - The purpose of this study was to clarify temporal changes of carotid wall
enhancement using dynamic magnetic resonance (MR) and to correlate its findings
with pathological conditions. Cervical carotid arteries of 84 consecutive
patients were studied with a 1.5 T MR imager using phased array coils. Axial
spoiled gradient-echo (SPGR) images (30-58 second scan time) with fat saturation
were repeated 4-8 times after the injection of contrast material. We evaluated
the presence and thickness of hypointense inner rims and hyperintense outer rims
of the carotid wall, temporal changes of outer rim enhancement, and their changes
in relation to pathological conditions. Hypointense inner rims and enhanced outer
rims were clearly visualized in 87% (73/84) of our subjects. Enhancement of the
outer rim was minimal in early phases and gradually increased. Patient age had a
significant correlation with outer rim thickness. In the portions with large
atheromatous plaques, inner rims were disrupted or thickened. A marked thickening
of the outer rim was observed in one patient with arteritis. The outer rims
adjacent to malignant tumors were often obscured. Our study suggests that dynamic
MR images of the cervical carotid artery can uniquely demonstrate angiogenesis of
the wall itself. The outer rim of the artery shows relatively rapid enhancement,
and its thickness correlates with age.
PMID- 10194713
TI - Autoperfused balloon catheter for intravascular MR imaging.
AB - An intravascular magnetic resonance (MR) imaging catheter for high-resolution
imaging of vessel walls was developed. The catheter design is based on an
autoperfusion balloon catheter that allows passive perfusion of blood during
balloon inflation. The blood enters a central lumen through multiple sideholes of
the catheter shaft proximal to the balloon. A remotely tuned, matched, and
actively decoupled, expandable single-loop radiofrequency coil was mounted onto
the balloon to receive intravascular MR signals. The autoperfusion rate through
the catheter was determined experimentally relative to perfusion pressure. The
catheter concept was evaluated in vitro on human femoral artery specimens and in
vivo in the internal carotid artery of two pigs. The proposed catheter design
allowed for maintained blood perfusion during the acquisition of high-resolution
intravascular images. During perfusion, image quality remained unaffected by
flow, motion, and pulsatility artifacts. The availability of an autoperfused
intravascular catheter design can be considered an important step toward high
resolution atherosclerotic plaque imaging in critical vessels such as the carotid
and coronary arteries.
PMID- 10194714
TI - MR measurement of regional relative cerebral blood volume in epilepsy.
AB - The purpose of this study was to evaluate the utility of magnetic resonance (MR)
relative cerebral blood volume (rCBV) maps for studying regional hemodynamic
changes in interictal and ictal epilepsy patients. Ten epilepsy patients were
examined on a 1.5 T MR system. Nine patients were investigated interictally and
one patient ictally. In the nine interictal patients, the dynamic plane was
defined coronally through the hippocampus symmetrically. For the ictal patient,
an axial dynamic plane was defined and the patient was scanned during seizure.
Positron emission tomography (PET) studies were performed in 8 of the 10
patients. Lower rCBV of the left hippocampus was predicted by rCBV maps in seven
of the nine interictal patients. The mean ratios of rCBV were 1.96 for left
hippocampus/white matter and 2.49 for right hippocampus/white matter. The
difference between these two ratios is statistically significant (P = 0.01, t
test). In two of the nine interictal temporal lobe epilepsy patients, lower rCBV
areas were observed in the right hippocampus. In the ictal patient, the regional
rCBV map demonstrated increased blood volume in the lesions. In eight of eight
patients who underwent PET studies, MR rCBV findings were consistent with PET
findings. The results show that regional hemodynamic changes in epilepsy can be
evaluated with dynamic contrast-enhanced MR imaging. MR rCBV maps are sensitive
to characterize seizure foci both ictally and interictally.
PMID- 10194715
TI - A multicenter measurement of magnetization transfer ratio in normal white matter.
AB - To assess the importance of intercenter variations when measuring magnetization
transfer ratio (MTR) in the brain, six European centers measured MTR in normal
white matter. MTR ranged from 9 to 51 percent units (25 sequences). The effective
flip angle of the saturating pulse divided by the pulse repetition time (ENRsat
degrees/msec) was a good predictor of MTR (MTR = 3.25 ENRsat).
PMID- 10194716
TI - Comparison of iron oxide particles (AMI 227) with a gadolinium complex (Gd-DOTA)
in dynamic susceptibility contrast MR imagings (FLASH and EPI) for both phantom
and rat brain at 1.5 Tesla.
AB - The goal of the study was to compare, in phantom and normally perfused rat brain
tissue, a superparamagnetic iron oxide particle-based contrast agent (AMI 227)
with a low-molecular-weight gadolinium chelate, gadolinium
tetraazacyclododecanetetraacetic acid (Gd-DOTA), in two susceptibility contrast
magnetic resonance imaging (MRI) modes [fast low-angle shot sequence (FLASH) and
echoplanar imaging (EPI)]. A phantom consisting of dilution series of both
contrast agents was manufactured. Dilutions were obtained with isotonic serum
from the available agent solutions (0.5 mmol Gd/mL Gd-DOTA; 350 mumol Fe/mL AMI
227). Eighteen rats were studied. Contrast agent (0.1 mL) was bolus injected in
each rat, and dynamic MRI was performed (first pass of the contrast agent) in rat
brain. The doses of AMI 227 injected were extrapolated from the phantom
experiment: 0.2 mmol/kg body weight of Gd-DOTA and 7, 14, and 28 mumol Fe/kg body
weight of AMI 227 were injected. For both sequences, signal-to-noise ratios (S/N)
were measured on each tube of the phantom and on rat brain from each image of the
dynamic imaging. S/N was plotted versus contrast dilution (phantom) and versus
time (rats). In the FLASH sequence, a well-shaped curve (S/N decrease, S/N peak
decrease, S/N increase) of the first pass of the contrast agent was demonstrated
for Gd-DOTA and for AMI 227 (7 mumol Fe/kg body weight). In the EPI sequence, a
well-shaped curve was demonstrated for Gd-DOTA, and a plateau effect was noted
for both concentrations of AMI 227. With the FLASH technique, dynamic
susceptibility contrast imaging of rat brain can be performed with very low
concentrations of AMI 227 compared with the Gd-DOTA concentration (0.2 mmol Gd/kg
body weight) used in clinical practice. This could be of interest in perfusion
imaging, because it may allow for first-pass susceptibility imaging after
administration of a small volume in a narrow bolus.
PMID- 10194717
TI - Transfer insensitive labeling technique (TILT): application to multislice
functional perfusion imaging.
AB - Cerebral blood flow can be studied in a multislice mode with a recently proposed
perfusion sequence using inversion of water spins as an endogenous tracer without
magnetization transfer artifacts. The magnetization transfer insensitive labeling
technique (TILT) has been used for mapping blood flow changes at a microvascular
level under motor activation in a multislice mode. In TILT, perfusion mapping is
achieved by subtraction of a perfusion-sensitized image from a control image.
Perfusion weighting is accomplished by proximal blood labeling using two 90
degrees radiofrequency excitation pulses. For control preparation the labeling
pulses are modified such that they have no net effect on blood water
magnetization. The percentage of blood flow change, as well as its spatial
extent, has been studied in single and multislice modes with varying delays
between labeling and imaging. The average perfusion signal change due to
activation was 36.9 +/- 9.1% in the single-slice experiments and 38.1 +/- 7.9% in
the multislice experiments. The volume of activated brain areas amounted to 1.51
+/- 0.95 cm3 in the contralateral primary motor (M1) area, 0.90 +/- 0.72 cc in
the ipsilateral M1 area, 1.27 +/- 0.39 cm3 in the contralateral and 1.42 +/- 0.75
cm3 in the ipsilateral premotor areas, and 0.71 +/- 0.19 cm3 in the supplementary
motor area.
PMID- 10194718
TI - Quantitative analysis of cerebral microvascular hemodynamics with T2-weighted
dynamic MR imaging.
AB - The purpose of this study was to quantify cerebral microvascular hemodynamics
with T2-weighted dynamic susceptibility contrast-enhanced magnetic resonance
imaging (DSC-MRI) using a half-Fourier acquisition single-shot turbo spin-echo
(HASTE) sequence. We performed T2-weighted DSC-MRI with HASTE sequence in 19
normal subjects. After bolus injection of gadopentetate dimeglumine, HASTE images
of two sections were acquired for the simultaneous creation of concentration-time
curves in the internal carotid artery and in brain tissue. Absolute regional
cerebral blood volume (rCBV), regional cerebral blood flow (rCBF), and mean
transit time (MTT) values of brain tissue were calculated on a base of the
indicator dilution theory, and all values were corrected on the assumption that
rCBF of white matter is constant in 22 mL/100 g tissue/min without age-dependent
alteration. A decrease in rCBV and rCBF of gray matter was age dependent, while
rCBV of white matter did not show significant change with aging. The mean rCBF
value in gray matter was 37.3 +/- 8.4 mL/100 g tissue/min. The mean rCBV value
was 4.1 +/- 0.8 mL/100 g tissue in gray matter and 2.9 + 0.4 mL/100 g tissue in
white matter. The rCBV and rCBF values of gray and white matter obtained from T2
weighted DSC-MRI with HASTE sequence were slightly lower than the published data
calculated by gradient-echo sequence. We were able to perform absolute
quantifications of the capillary blood volume and flow, using a HASTE sequence,
which would not have been possible with a gradient-echo sequence. This technique
provides a new method for estimating cerebral microvascular hemodynamics.
PMID- 10194719
TI - The carpal ligaments in MR arthrography of the wrist: correlation with standard
MRI and wrist arthroscopy.
AB - We assessed the value of three-compartment magnetic resonance (MR) wrist
arthrography in comparison with non-enhanced magnetic resonance imaging (MRI) for
the evaluation of 13 individual wrist ligaments in 35 patients with refractory
wrist pain. In 20 of these patients MR findings were correlated with the findings
from multiportal wrist arthroscopy. For MR imaging (1.5-T magnet) a three
dimensional volume acquisition with a gradient-recalled echo sequence and 0.6-1.0
mm effective slice thickness was used. The delineation of individual wrist
ligaments was rated as "good" in 10% of non-enhanced MR and 90% of MR
arthrography images. Ligament evaluation was possible with high diagnostic
confidence in 11% by non-enhanced MR imaging and 90% by MR arthrography. With
wrist arthroscopy as the standard of reference, average
sensitivities/specificities/accuracies for the diagnosis of full-thickness
ligamentous defects were 0.81/0.75/0.77 for non-enhanced MR imaging and
0.97/0.96/0.96 for MR arthrography. Our findings suggest that MR arthrography is
more accurate than standard MRI in delineating and evaluating the ligaments of
the wrist.
PMID- 10194720
TI - Sub-millimeter fMRI at 1.5 Tesla: correlation of high resolution with low
resolution measurements.
AB - Functional magnetic resonance imaging of the visual cortex with an in-plane
resolution of 0.4 x 0.4 mm2 was performed using a simple visual stimulus
resulting in clear maps of activation. A collapsing filter was used to compare
these high-resolution images with low-resolution images collected during the same
session. A good correspondence between the high- and low-resolution functional
maps was found with respect to the center of localization of activation. However,
only 20% of the size of activated areas in the low-resolution experiment was
observed at high resolution, which was partly caused by the difference in signal
to-noise ratio. The high-resolution images produce signal changes much higher
than the low-resolution images due to reduced partial volume effects.
Additionally, the high-resolution functional maps were compared with detailed
anatomical and venous information. The activated areas were predominantly
observed at venous vessels within the sulci with a diameter on the order of the
pixel size.
PMID- 10194721
TI - MR perfusion imaging of pulmonary parenchyma using pulsed arterial spin labeling
techniques: FAIRER and FAIR.
AB - Magnetic resonance imaging of pulmonary parenchyma perfusion using pulsed
arterial spin labeling (ASL) techniques is presented. ASL uses magnetically
labeled water as an endogenous, freely diffusible tracer. Presented are
comparative results of ASL methods called Flow sensitive Alternating Inversion
Recovery (FAIR), and FAIR with an Extra Radiofrequency pulse (FAIRER). Six
healthy human volunteers were imaged. Perfusion-weighted images at different time
delays, TI, were calculated from the subtraction of the control and tag images,
which were acquired within a single breathhold. Detailed pulmonary structures can
be visualized with negligible cardiac or respiratory motion artifacts. Different
patterns of signal enhancement between the pulmonary vessels and parenchyma are
shown in the perfusion images acquired at different TIs.
PMID- 10194722
TI - Sonographic and MR findings of an extensive, HIV-related prostatic abscess.
AB - We present findings in a patient positive for the human immunodeficiency virus in
whom a prostatic abscess involving the entire gland was diagnosed by transrectal
ultrasonography and magnetic resonance imaging (MRI); he was subsequently treated
by transurethral resection, drainage, and antibiotics. To our knowledge, this is
the first report of a pelvic phased-array coil MRI performed in a patient with
prostatic abscess.
PMID- 10194723
TI - Magnetic resonance angiography of primary varicella vasculitis: report of two
cases.
AB - Two patients with onset of hemiparesis 3 weeks following primary varicella
infection demonstrated contralateral temporal lobe and basal ganglia infarctions
on magnetic resonance imaging. In both cases, magnetic resonance angiography
(MRA) was performed and demonstrated flow abnormalities ipsilateral to the
infarcts. Digital subtraction angiography was performed in one case; however, the
findings were significantly less conspicuous than those of the MRA. MRA proved to
be sensitive to the diagnosis of varicella-induced vasculitis in two consecutive
cases and provided a noninvasive means of following the progression of the
disease process in response to therapy.
PMID- 10194724
TI - Contemporaneous positron emission tomography and MR imaging at 1.5 T.
AB - Simultaneous acquisition of positron emission tomography (PET) and magnetic
resonance (MR) images using an MR-compatible PET system will obviate the need for
image registration and will allow unique studies of structure and function of
living organisms in one setting. Here we report on simultaneous acquisition of
PET and MR images on a clinical 1.5 T system using a 54 mm diameter prototype MR
compatible PET system (McPET). Phantom experiments were performed in order to
determine the effect of the McPET system on MR images. The results demonstrated
the system to be fully MR compatible, in both its detector head construction and
operation. The McPET construction offers a promising method for design of a large
scale MR-compatible PET system that will be useful in functional studies of the
brain.
PMID- 10194725
TI - The reinforcement of dentures.
AB - The material most commonly used for the fabrication of complete dentures is poly
(methyl methacrylate) (PMMA). This material is not ideal in every respect and it
is the combination of virtues rather than one single desirable property that
accounts for its popularity and usage. Despite its popularity in satisfying
aesthetic demands it is still far from ideal in fulfilling the mechanical
requirements of a prosthesis. The fracture of dentures may be due to the
mechanical properties of the acrylic resin or may be due to a multiplicity of
factors leading to failure of the denture base material. Generally, there are
three routes which have been investigated to improve the impact properties of
PMMA: the search for, or development of, an alternative material to PMMA; the
chemical modification of PMMA such as by the addition of a rubber graft
copolymer; and the reinforcement of PMMA with other materials such as carbon
fibres, glass fibres and ultra-high modulus polyethylene. The following review of
attempts to improve the mechanical properties of denture base material takes
account of papers published during the last 30 years.
PMID- 10194726
TI - A 5-year prospective randomized clinical trial on the influence of splinted and
unsplinted oral implants retaining a mandibular overdenture: prosthetic aspects
and patient satisfaction.
AB - Prosthetic outcome and patient satisfaction were evaluated in order to
investigate whether there is a need or advantage to splint two implants in the
mandible retaining a hinging overdenture. This study included 36 fully edentulous
patients randomly divided into three groups according to the attachment system
they received: magnets, ball attachments or straight bars (reference group). None
of the implants failed during the whole observation period in any of the groups.
After 5 years of observation, the Bar group presented the highest retention
capacity and the least prosthetic complications but revealed more mucositis and
gingival hyperplasia. Patient satisfaction rated similar for all groups although
the Magnet group showed lower retention forces. All patients would repeat the
same treatment even though the majority of the Magnet group would prefer a more
retentive solution because of limited denture stability.
PMID- 10194727
TI - Consistency of alginate impression materials and their evaluation.
AB - The apparent viscosity of 17 commercially available alginate impression materials
was examined using a rheometer. Each material was mixed for 15 s at a temperature
of 23 +/- 0.5 degrees C, using a specially designed alginate mixing instrument.
The water powder ratio was determined according to the manufacturer's
instruction. The mixed alginate paste was immediately transferred to the sample
stage of the rheometer or to a commercial perforated metal tray. Over the same
time scale adjusted according to the rheometer test, a discrimination test
(subjective test) was performed by 16 young dentists (each with more than 4 years
experience). The apparent viscosity of all materials rose as a function of time
after mixing and most of the material had properties similar to pseudoplastic
fluids. The relationship between the results of the subjective test and the
experimental values (objective test) with the rheometer was expressed in a
quadratic equation. The maximum value of the apparent viscosity derived from this
result was 1.52 x 10(3) Pa.s.
PMID- 10194729
TI - False localization of TMJ sounds to side is an important source of error in TMD
diagnosis.
AB - The results of the study indicate that the head tissues act as a band pass filter
that is far from flat. Instead there seems to be strong frequency variations in
attenuation of transmitted sounds. The sounds are subject to phase shift and time
delay, which can be used to decide from which TMJ the sound comes. Bilateral
electronic recording with high sampling rate (>> 44 kHz) is needed to accurately
and consistently identify the origin of a TMJ sound. Further studies on autopsy
specimens and large subject groups are motivated.
PMID- 10194728
TI - Unpolymerized surface layer of autopolymerizing polymethyl methacrylate resin.
AB - The aim of this study was to determine the thickness of the unpolymerized surface
layer of autopolymerizing polymethyl methacrylate (PMMA) resin. Powder: liquid
(P/L) ratios of 10:4-10 by weight of the PMMA were tested, and the PMMA resin was
polymerized at 55 degrees C either in water or in air under an air pressure of
100 kPa or 300 kPa. Five samples were polymerized for each of the test groups.
The thickness of the unpolymerized surface layer, i.e. inhibition depth of PMMA,
was measured by a light microscopic technique with polarized light. The
inhibition depth of the samples polymerized in air under 100 kPa pressure varied
from 39 to 174 microns, and the samples polymerized under 300 kPa pressure had an
inhibition depth of 91-391 microns. The P/L ratio and the polymerization pressure
had a significant effect on the inhibition depth (P < 0.001). No inhibition layer
was observed in the samples polymerized in water. The results suggest that in
order to obtain an adequate degree of polymerization on the surface of
autopolymerizing PMMA resin, the polymerization process should be carried out in
water.
PMID- 10194730
TI - Age-hardening associated with grain boundary precipitation in a commercial dental
gold alloy.
AB - The aim of this study was to make clear the age-hardening mechanism in a dental
high carat gold alloy. For this purpose, age-hardening behaviour of a commercial
dental high carat gold alloy, 65.5 wt% Au-14.0 wt% Ag-10.0 wt% Cu-8.9 wt% Pt, was
investigated by means of hardness testing, X-ray diffraction study and scanning
electron microscopy. Age-hardening was generated by the coherency strain
resulting from the transformation of the alpha single phase to the Ag-rich alpha
1 phase and the AuCu I type ordered phase. The coherency strain seemed to be
associated with the nucleation of the AuCu ordered structure initially, and then
was brought about with the simultaneous formation of the Ag-rich alpha 1 phase
and the AuCu I type ordered phase. Hardening was attributed mainly to the very
fine coherent precipitates of a lamellar structure composed of the Ag-rich alpha
1 phase and the AuCu I type ordered phase at grain boundaries, and softening,
which occurred following prolonged ageing, was due to the coarsening of the fine
lamellar structure by releasing the strain at the interfaces of the adjacent
lamellae.
PMID- 10194731
TI - Comparison of biting forces in different age and sex groups: a study of biting
efficiency with mobile and non-mobile teeth.
AB - This study aimed (1) to investigate the influences of sex, age and number of
teeth on biting ability through a descriptive survey, and (2) to compare the
biting ability between the subjects with and without mobile teeth in a case
control study. A total of 687 subjects cooperated in the descriptive survey. Each
subject bit on a pressure detecting sheet with their maximum biting force. Three
indices of biting ability: biting pressure (MPa), biting force (N) and occlusal
contact area (mm2) were calculated from the impressed marks on the sheet using a
high vision video processor system. These indices were correlated well with the
number of teeth according to the multiple regression analysis. In the case
control study, matching procedures with sex, age and number of teeth were
performed between the subjects with and without mobile teeth. No differences in
the three indices were observed between the two well-balanced groups. The results
showed that the number of teeth is most important to maintain biting ability, and
that the presence of mobile teeth does not always reduce biting ability.
PMID- 10194732
TI - Comparative wear ranking of dental restoratives with the BIOMAT wear simulator.
AB - Fundamental in vitro wear tests are important for the study of wear mechanisms,
provision of data during material development and screening of materials prior to
clinical trials. The aim of this project was to compare the wear of six dental
restoratives using the BIOMAT wear simulator which was developed to simulate jaw
movements and stresses generated in the occlusal contact areas during the chewing
process. The correlation of wear to hardness of the restoratives was also
assessed. Wear ranking from the least to the most volumetric wear was as follows:
high copper unicompositional alloy, Tytin (T) < high copper admixed alloy,
Valiant PhD (V) < microfilled composite resin, Silux Plus (S) < gallium alloy,
Galloy (G) < heavily filled composite resin, Z100 (Z) < hybrid composite resin,
P50 (P). The high copper amalgam alloys had significantly greater wear resistance
when compared with all the composite resins. The gallium alloy, microfilled and
heavily filled composite resins also exhibited significantly less wear than the
hybrid resin. Wear ranking with the BIOMAT simulator was similar to that obtained
in vivo. Ranking from the hardest to softest material: high copper
unicompositional alloy, T < gallium alloy, G < high copper admixed alloy, V <
hybrid composite resin, P < heavily filled composite resin, Z < microfilled
composite resin, S. The amalgam alloys were significantly harder than the heavily
filled and microfilled composite resins. There was no apparent correlation
between wear performance and material hardness.
PMID- 10194733
TI - A calculation method for the range of occluding phase at the lower incisal point
during chewing movements using the curved mesh diagram of mandibular excursion
(CMDME).
AB - The purpose of this study was to develop a method for calculating the range of
the occluding phase in chewing movements. In this study, we defined 'range' as
the distance of the movement at the lower incisal point while the mandible moves
with tooth contact. First, mandibular excursions were measured using an opto
electronic movement analysis system, which can measure mandibular movement with
six degrees-of-freedom at a sampling frequency of 100 Hz. With use of this
measurement data, the curved mesh diagram of mandibular excursion (CMDME)
previously reported was made. Then, chewing movements were measured using the
same analysis system. The movements were separated into their component chewing
cycles. Finally, we calculated the distance between each cycle and the CMDME. The
occluding range of our subject was 0.4 mm at the closing phase and 3.4 mm at the
opening phase. These results suggest that tooth contact occurs during chewing
movement and demonstrate that the range of the occluding phase for the opening
and closing phases of a subject can be calculated without morphological data from
a dental cast.
PMID- 10194734
TI - Quantitative evaluation of the effect of bolus size and number of chewing strokes
on the intra-oral mixing of a two-colour chewing gum.
AB - One of the major aims of the dental profession is the maintenance of oral
function, specifically chewing ability. However, there are no generally accepted
measures of chewing ability or even general agreement as to what level of tooth
loss is deemed to require clinical intervention. There is therefore a need for
simple objective tests of oral function. In this study a modification of the two
colour chewing gum test devised by Liedberg & Owall (1991, 1995) is described. In
this test chewing gum containing two contrasting colours is chewed. On removal
from the mouth the bolus is placed in a transparent plastic bag, flattened and a
digital image is taken. Several image processing techniques are described and
evaluated as measures of the amount of mixing present in the chewed gum.
Flattening the gum was found to increase the accuracy of subjective evaluation,
which was similar to that achieved by the image processing techniques.
PMID- 10194735
TI - Association between loss of occlusal support and symptoms of functional
disturbances of the masticatory system.
AB - The purpose of this study was to evaluate the association of loss of occlusal
support with symptoms of functional disturbances of the masticatory system, in
particular with the ones related to the temporomandibular dysfunction. A total of
483 adult subjects randomly selected from the population living in the
municipality of Segrate, northern Italy, were studied. Subjects were interviewed
by questionnaire about oral conditions and occurrence of symptoms of disturbances
of the masticatory system. Also, denture was examined by dentists during the
interview. Loss of occlusal support was observed in 60.2% of the subjects,
symptoms of functional disturbances in 68.7% and temporomandibular dysfunction in
55.1%. At univariate analysis loss of occlusal support was mainly associated with
a feeling of stiffness or fatigue of the jaws (P < 0.001), difficulty in closing
the mouth (P < 0.005) and difficulty on mastication (P < 0.0001). Association
with temporomandibular dysfunction as a whole was significant also (P < 0.001).
Multiple age- and sex-adjusted logistic analysis disclosed a significant strong
impact of loss of occlusal support on difficulty with mastication (odds ratio =
7.0, P < 0.0001). At that analysis, no significant relationship resulted with
symptoms of temporomandibular dysfunction. These findings confirm that presence
of an adequate occlusal support is a relevant factor in maintaining an efficient
chewing, and also suggest that it may play any indirect role in preventing
occurrence of symptoms of temporomandibular dysfunction.
PMID- 10194737
TI - An investigation of the stress values on a tooth restored by amalgam.
AB - The study was carried out in two stages: (1) MOD amalgam cavities were prepared
on maxillary second premolars and three strain gauges were attached to the
palatal surface of each tooth. The teeth were filled using amalgam with and
without base material (glass-ionomer). Stresses occurred during the hardening
phase and also through mastication and were measured by strain-gauge rosettes.
(2) The stresses which occurred at the same points were calculated by the finite
element method and compared with the values obtained experimentally. The highest
stress values were observed when no base material was used.
PMID- 10194736
TI - The effect of composite resin application and radiation techniques on dye
penetration in Class II direct composite resin restorations.
AB - This study examined the effect of the application of resin composite and
radiation techniques on dye penetration in class II direct composite resin
restorations. For the restorative procedure, the light-cone and the incremental
layering techniques were used. The null hypothesis of this experiment was, that
both techniques have the same influence on dye penetration. Evaluation of dye
penetration in the restoration/tooth interface was performed in 20 extracted
premolars and molars. On each tooth, two class II cavities were prepared. The
cervical margin of the proximal boxes were located in dentin or in enamel. When
the gingival margin of the cavity was located in enamel, a significant lower
level of dye penetration of the the test group was found (Wilcoxon rank test, P =
0.0102). This study showed that the application of a transparent cone seems to be
more effective than the three increments technique in the mechanical separation
of the first composite increment. Transmitting the curing light into the proximal
box, seems to have no positive effect on dye penetration in class II direct
composite resin restorations.
PMID- 10194738
TI - A review of recent findings on substance abuse treatment for pregnant women.
AB - Recent years have brought an increased interest in the treatment needs of
pregnant substance abusers. This article reviews the literature on this subject,
providing an overview of what is known about the prevalence of substance abuse
during pregnancy; the factors in women's lives, especially pregnant women, that
lead to substance abuse and that facilitate and impede treatment success; and the
components of successful treatment programs. The prevalence of prenatal illicit
drug use is known to be about 5% of all pregnant women nationwide, with higher
rates for selected subgroups. Local studies have shown much higher rates.
Substance abuse is associated with poverty, with the substance abuse of
significant others, and with family violence. Perinatal substance abusers
experience poorer birth outcomes. The negative consequences for babies do not
stop at birth; home environments may be chaotic and often children are removed
from their mother's care if substance abuse continues after birth. While the
literature on prevalence, correlates, and outcomes of perinatal substance abuse
is plentiful, there continues to be sparse information on successful treatment
approaches. Sample sizes are small and there are few studies with adequate
comparison groups. The small number of outcome studies we review suggest that, as
with the broader treatment literature for other populations, success (as measured
by abstinence) is associated with retention. Retention is facilitated by the
provision of support services, such as child care, parenting classes, and
vocational training. There is no clear empirical basis for concluding that one
type of treatment (for example, residential treatment) is more effective than
another.
PMID- 10194739
TI - Methadone maintenance. Does dose determine differences in outcome?
AB - We conducted a naturalistic study to determine if higher methadone doses were
more effective than lower doses in the outcome variables of illicit drug use,
treatment retention, missed medication days, and ratings of patient progress by
assigned counselor among 265 patients in a Department of Veterans Affairs
Methadone Maintenance Treatment Program. Results indicated no significant
differences on any outcome variable by methadone dose. However, we found a
significant effect by assigned therapist. Some therapists achieved better outcome
results on these same variables compared to other assigned therapists independent
of dose level. We conclude that, while methadone maintenance dose is an important
variable, researchers need to pay more attention to the interpersonal aspects of
methadone maintenance treatment.
PMID- 10194740
TI - Knowledge of tuberculosis among drug users. Relationship to return rates for
tuberculosis screening at a syringe exchange.
AB - Tuberculosis is an important health issue among drug users. We sought to evaluate
active drug users' (DUs) knowledge of tuberculosis (TB) and to assess the
relationship between TB knowledge and attitudes and tuberculin skin test (TST)
return rates at a syringe exchange program. DUs were recruited at a syringe
exchange program in New York City, were interviewed and offered TSTs, and
received $15.00 upon returning for TST reading. The questionnaire evaluated
knowledge of TB transmission, prevention, and treatment. From March 13, 1995 to
January 31, 1996, 610 of 650 (94%) of DUs approached agreed to participate. Of
these, 80% had previous TSTs within the past 2 years and 20% were known to be HIV
infected. Almost all knew that TB is contagious and more than two thirds knew
that TB is treatable and that TB preventive therapy existed. However, fewer than
half knew that HIV-related TB could be treated, 30% thought TB could be treated
without a medical doctor, and the majority (70%) thought a reactive TST implied
infectivity. The rate of return for TST reading was 93%. In multivariate
analysis, those who knew that HIV-related TB was curable were more likely to
return for TST reading (odds ratio 2.0; 95% confidence interval 1.04 to 3.95; p =
.03). The high acceptance and return rates suggest that TB services can be
incorporated into syringe exchange programs. However, several important gaps in
TB knowledge existed in this population at high risk of TB, which may impact on
adherence and which support the need for TB education for drug users.
PMID- 10194741
TI - A new multiscale measure of adult substance abuse.
AB - Several assessment measures exist in the adult substance abuse field, but the
majority of them are either screening tools or are limited to alcohol use.
Current trends in drug abuse patterns and the service care industry suggest the
need for sophisticated and comprehensive instrumentation. This paper focuses on
the design and psychometric properties of a 270-item, multiscale, self-report
inventory for measuring a wide range of problems associated with adult substance
abuse. The Personal Experience Inventory for Adults consists of problem severity
and psychosocial risk scales, validity indicators, and problem screens. Basic
reliability and validity data will be summarized.
PMID- 10194742
TI - Work dysfunction and addiction. Common roots.
AB - A review of the literature identified similarities in the self-efficacy roots of
substance abuse and vocational dysfunction, along with a potential benefit to
providing vocational interventions as part of substance abuse treatment. Based
upon the evidence presented, the author recommends the use of social cognitive
counseling; using client functioning and level of care to guide vocational
interventions; closely monitoring clients who are working; providing for ongoing
social support; and committing to the availability of long-term aftercare and
crisis intervention counseling to insure developmental gains are not lost.
PMID- 10194743
TI - Reflections on volatile substance dependency treatment. Negotiating the boundary
between inner and outer reality.
AB - A brief review of the causal and treatment literature relating to volatile
substance dependency suggests the interaction between individual and system
requires careful attention and understanding. A model is tentatively and
provisionally adumbrated to help clarify the main factors involved from a dynamic
biopsychosocial perspective. Ego boundary disturbances emerge from and
reciprocally influence behaviour and social interactions. These disturbances can
be avoided temporarily, although inevitably deepened in the long-term, by
substance dependence. Two case examples, selected because they differ in many
respects, including relative treatment effectiveness, illustrate this integrative
perspective. The discussion focuses on explaining the differing outcomes in terms
of the extent to which the inner-outer boundary is open to modification and how
far it can be successfully negotiated and clarified. A major factor in
differentiating between inside and outside is thought to be causal perceptions or
"attributions." Successful differentiation tends to facilitate change, as opposed
to reinforcing maladaptive homeostasis. Key issues for therapists overlap with
addictions treatment in general, including emotional blocks or barriers in
patients, difficulty engaging systems in a strategic manner, and
countertransference problems. It is argued that these difficulties in therapy
might respond to integrative psychotherapeutic responses, provided the
differences in perspective are sufficiently understood.
PMID- 10194744
TI - The development and evaluation of an alcohol and drug prevention and treatment
program for women and children. The AR-CARES program.
AB - This study examined the evolution of the Arkansas Center for Addictions Research,
Education, and Services (AR-CARES) over a 5-year period and evaluated its impact
on women and children. The program was designed to provide comprehensive
substance use prevention and treatment services to low-income pregnant and
parenting women and their children. The program changed significantly over this
time, based upon input from clients and staff, as well as in response to changing
community resources. The evaluation suggests that the program had an impact on
the substance use of study participants, birth outcomes, and the growth and
development of children.
PMID- 10194745
TI - Visual and olfactory responses of haematophagous Diptera to host stimuli.
AB - Key biotic and environmental constraints on the host-orientated behaviour of
haematophagous Diptera are summarized. For each major group of biting Diptera,
responses to host stimuli are reviewed, including activation and ranging
behaviour, long-range and short-range olfactory responses and visual responses.
Limitations to the comparison of results between groups of species, and the
practical problems of experimental method and equipment are discussed.
PMID- 10194746
TI - Identification of five species of the Anopheles dirus complex from Thailand,
using allele-specific polymerase chain reaction.
AB - The Anopheles dirus complex of mosquitoes contains some of the most important
vectors of malaria in Southeast Asia. To distinguish five species of the complex
that occur in Thailand, a method using the polymerase chain reaction (PCR) was
developed. The method utilizes allele-specific amplification to detect fixed
differences between the species in the DNA sequence of the ribosomal DNA internal
transcribed spacer 2. Primers were designed to amplify fragments of diagnostic
length from the DNA of the different species. The method was tested on 179
mosquitoes of the An. dirus complex from many parts of Thailand and shown to be
effective. Every specimen was unambiguously identified as species A, B, C, D or F
(i.e. An. dirus s.s. species B, C, D or An. nemophilous, respectively) by the PCR
method, with confirmation of 58/61 identifications from polytene chromosome
characteristics. For the other three specimens (3/44 from Kanchanaburi 5
locality), there was disagreement between the PCR and chromosomal methods of
species identification (probably due to errors in the chromosomal
identifications). Primers can be combined in a single PCR reaction providing a
rapid, sensitive and straightforward method of species identification. Only small
quantities of DNA are required, leaving most of the mosquito to be used for other
analyses.
PMID- 10194747
TI - Efficiency and cost of strategic use of acaricide for tick control in N'Dama
cattle in The Gambia.
AB - The efficiency of strategic and strategic/selective applications of flumethrin
spray formulation for controlling ticks were assessed, respectively, in two
groups of fourteen N'Dama cattle (Group S and Group S/S) by comparison of the
number of feeding ticks with thirteen untreated N'Dama cattle (Group U) over a
period of 11 months (June 1996 to April 1997). During the expected peak of tick
abundance, acaricide was applied fortnightly on the whole body in animals in
Group S and only on the most infested body areas in cattle in Group S/S. Weight
changes and skin lesions, directly associated with tick attachment, were recorded
in cattle in the three groups. The costs of the two tick control schemes were
estimated. Maximum level of ticks, all species together, feeding on cattle was
observed in the rainy season. Both in Group S/S and Group S, cattle carried a
lower (P < 0.001) number of feeding ticks than animals in Group U over the whole
study period. Percentage of tick control, over the entire period of tick
investigation, was satisfactory in both acaricide-treated groups, reaching 61.2
and 75.2% in Groups S/S and S, respectively. However, the proportion of control
varied according to tick species or genus. Significantly lower prevalence of skin
lesions was observed on the ano-genital and udder region in cattle in Group S/S
(P < 0.05) and Group S (P < 0.01) in comparison with cattle in Group U. Mean
amount of acaricide solution used and relative estimated cost of treatment in
cattle in Group S/S were, respectively, 25- and 14-fold lower than those in
cattle in Group S. At the end of the study, animals in Groups S/S and S were,
respectively, 7.2 and 15.9 kg heavier than animals in Group U. The difference was
statistically significant (P < 0.02) only between Groups S and U. However, the
efficiency, low cost and derived benefits of the strategic/selective acaricide
application scheme indicated that it might be the most cost effective.
PMID- 10194748
TI - Age structure of overwintered face fly populations estimated by pteridine
concentrations and ovarian dynamics.
AB - Pteridines in the head capsules of face flies, Musca autumnalis DeGeer, were
measured spectrofluorometrically to provide estimates of age. The flies also were
dissected to determine ovarian development and fat body hypertrophy.
Physiological ages in terms of degree-day accumulations were estimated among late
autumn, winter, and early spring face flies. The reproductive history of eight
overwintered face fly populations near Ames, Iowa, U.S.A., suggested that each
had behaved as a single cohort, maturing their eggs and ovipositing according to
a simple heat unit model. 83.8 +/- 16.4 degree-days above a 12 degrees threshold
(DD > 12 degrees) were estimated to elapse between 1 January and the date at
which 50% of overwintered cohorts had oviposited. Pteridine deposits indicated
that diapausing females in late autumn had acquired a mean 96 +/- 36 DD > 9.8
degrees and the males 135 +/- 39 DD > 9.8 degrees. Soon after emergence from
hibernaculae, females were average physiological ages of 135 +/- 25 DD > 9.8
degrees and the males were 152 +/- 28 DD > 9.8 degrees. Mean physiological age of
overwintered females was 155 +/- 37 DD > 9.8 degrees compared with 110 +/- 38 DD
> 9.8 degrees among parous flies in summer. Overwintered males in spring were an
average 175 +/- 41 DD > 9.8 degrees compared with 144 +/- 65 DD > 9.8 degrees
among summer flies.
PMID- 10194749
TI - Pteridine fluorescence for age determination of Anopheles mosquitoes.
AB - The age structure of mosquito populations is of great relevance to understanding
the dynamics of disease transmission and in monitoring the success of control
operations. Unfortunately, the ovarian dissection methods currently available for
determining the age of adult mosquitoes are technically difficult, slow and may
be of limited value, because the proportion of diagnostic ovarioles in the ovary
declines with age. By means of reversed-phase HPLC this study investigated the
malaria vectors Anopheles gambiae and An. stephensi to see if changes in
fluorescent pteridine pigments, which have been used in other insects to
determine the age of field-caught individuals, may be useful for age
determination in mosquitoes. Whole body fluorescence was inversely proportional
to age (P < 0.001, r2 > 91%) up to 30 days postemergence, with the regression
values: y = 40580-706x for An. gambiae, and y = 52896-681x for An. stephensi. In
both species the main pteridines were 6-biopterin, pterin-6-carboxylic acid and
an unidentified fluorescent compound. An. gambiae had only 50-70% as much
fluorescence as An. stephensi, and fluorescent compounds were relatively more
concentrated in the head than in the thorax (ratios 1:0.8 An. gambiae; 1:0.5 An.
stephensi). The results of this laboratory study are encouraging. It seems
feasible that this simpler and faster technique of fluorescence quantification
could yield results of equivalent accuracy to the interpretation of ovarian
dissection. A double-blind field trial comparing the accuracy of this technique
to marked, released and recaptured mosquitoes is required to test the usefulness
of the pteridine method in the field.
PMID- 10194750
TI - Induced immunity against the mosquito Anopheles stephensi: reactivity
characteristics of immune sera.
AB - This study shows the progression of immune responses in mice during five
sequential immunizations with Anopheles stephensi mosquito extracts,
characterized by ELISA, Western blot and immunohistochemistry. When exposed
repeatedly to mosquito bites, control mice developed antibodies which reached
titres of 1:10(5), reacted weakly in Western blot analysis and were localized to
the salivary glands. Mice immunized with mosquito head plus salivary glands,
midgut, ovary, fat body, midgut microvilli (Mv) and midgut basolateral plasma
membrane (Blm), showed increased titre with each successive boost. Epitopes were
shared between sera or were specific to the immunizing or heterologous extract.
Anti-Mv and Blm sera recognized proteins labelled by anti-midgut serum and gave
specific reactions with the midgut and head. Cross-reactivity was confirmed
immunohistochemically.
PMID- 10194751
TI - Sugar meals and longevity of the sandfly Phlebotomus papatasi in an arid focus of
Leishmania major in the Jordan Valley.
AB - The sugar diet and life-span of Phlebotomus papatasi were studied in a typical
zoonotic focus of Leishmania major in an arid area of the Jordan Valley during
1996-1997. Plant-tissue residues (cellulose particles) were identified in the
stained guts of 23% of P. papatasi and significant amounts of sugar were found in
the gut of 16%. Feeding on different plants was demonstrated by using their
branches, suffused with cellulose stain, as baits in the field. Ingested, stained
cellulose was detected in 10% of the sandflies (6% of males, 12.5% of females)
caught near bait-branches of common local plants, mostly Chenopodiaceae. The
similar rates of plant and sugar feeding, with the observed absence of aphids
(ruling out the availability of honeydew), implied that the sugar meals of
sandflies were obtained directly from plants. The relative paucity of sugar meals
in P. papatasi coincided with a short life-span, evaluated by daily growth lines
in the cuticle. The age of the oldest females was estimated to be 8 days, and 6
days for males. Under local conditions, the first gonotrophic cycle can be
completed in 6 days and the usual transmission of L. major is apparently
afterwards, when females ingest blood to initiate another cycle. Only about 9% of
P. papatasi females survived > 6 days.
PMID- 10194752
TI - Metaphase karyotypes and G-banding in sandflies of the Lutzomyia longipalpis
complex.
AB - Mitotic metaphase chromosomes (2n = 8) from brain cells of fourth instar sandfly
larvae of four geographical strains of the Lutzomyia longipaplis complex were
examined microscopically, with bright-field illumination, after staining by a new
G-banding technique involving exposure of air-dried chromosome preparations to
quinacrine and ultraviolet light. Differences of G-banding and/or position of the
centromere on chromosome 4 (the smallest chromosome pair) distinguished four
putative sibling species from Costa Rica, Colombia and Brazil (distinctive
populations from Jacobina and Lapinha Caves). The karyotype of the population
from Jacobina, Brazil, showed an apparently plesiomorphic pattern of G-banding.
On the basis of their recognizably different mitotic karyotypes, cytogenetic
identification of separate taxa in the L. longipalpis complex should be useful
for specific female vector competence and ecology studies.
PMID- 10194753
TI - Interspecific hybridization and genetic variability of Phlebotomus sandflies.
AB - The first successful hybridization is reported between Phlebotomus papatasi and
P. duboscqi, two important Old World sandfly vectors of leishmaniasis and other
diseases. Laboratory strains of P. papatasi and P. duboscqi were separable by six
diagnostic enzyme loci: Est-3, Idh-1, Mdh-2, Mpi, Tre-1 and Tre-3. Hybrids
between the two species were verified by the recovery of heterozygous isozyme
patterns for the diagnostic loci. No F2 or backcross progeny were obtained. P.
papatasi was separated from P. bergeroti by three diagnostic enzyme loci: Est-3,
Mpi and Pgd. The isozyme patterns of P. bergeroti contain elements of both P.
duboscqi and P. papatasi, although seven diagnostic loci (Est-3, Idh-1, Me, Mpi,
Pgd, Tre-1 and Tre-3) separated P. bergeroti from P. duboscqi. Genetic
variability profiles of the three species were established for 20 enzyme loci.
Three geographically distant strains of P. papatasi from Calcutta, Maharashtra
and Israel had isozyme genetic distances of < 0.05. The recently established
Calcutta strain showed an unexpectedly low genetic variability with only one (Idh
2) of 20 loci being polymorphic (average heterozygosity of 1.9%) in contrast to 5
8 polymorphic loci (10-12% heterozygosity) in the Maharashtra and Israel strains.
Mass and single pair crosses between the three P. papatasi strains were fertile
with normal progeny numbers. Thus we found no signs of speciation in P. papatasi.
PMID- 10194754
TI - Pyrethroid resistance mechanisms in the head louse Pediculus capitis from Israel:
implications for control.
AB - In Israel, the head louse, Pediculus capitis, developed resistance to DDT through
the extensive use of this insecticide until the 1980s. In 1991, permethrin was
introduced for control of DDT resistant P. capitis in Israel, leading to control
failure of this pyrethroid insecticide by 1994. Pyrethroid resistance of P.
capitis in Israel extends to phenothrin, which has not been used for louse
control. We identified a glutathione S-transferase(GST)-based mechanism of DDT
resistance in the Israeli head lice. This GST mechanism occurred before 1989,
while permethrin resistance in P. capitis developed after 1994, suggesting that
the main GST resistance mechanism selected by DDT use does not confer any
pyrethroid cross-resistance. Esterase activity levels were equivalent in
pyrethroid resistant and susceptible P. capitis field-collected in Israel, and in
a susceptible strain of P. humanus, the body louse, indicating no involvement of
any esterase-based mechanism in resistance. A weak monooxygenase-based permethrin
metabolism resistance mechanism was the only factor identified which could
account for any of the observed pyrethroid resistance in P. capitis. However, the
lack of synergism of phenothrin resistance by piperonyl butoxide suggests that a
non-oxidative mechanism is also present in the resistant lice. Therefore it seems
probable that pyrethroid resistance in Israeli P. capitis is due to a combination
of nerve insensitivity (knockdown resistance or 'kdr') and monooxygenase
resistance mechanisms.
PMID- 10194755
TI - Behavioural mode of action of deet: inhibition of lactic acid attraction.
AB - Using the mosquito Aedes aegypti in a novel olfactometer that measures movement
towards and away from a stimulus, we could not confirm that 'deet' is a repellent
of mosquitoes. In the absence of a host, deet was an attractant and in the
presence of a host, it was an inhibitor of attraction. This inhibition occurred
in the gaseous phase and was therefore not the result of the physical properties
of deet. We determined that L-lactic acid, a component of human sweat that is an
attractant to mosquitoes, is the target of this inhibition, implying that lactic
acid may be a bottleneck in the behavioural cascade preceding blood-sucking.
PMID- 10194756
TI - Morphology and ultrastructure of spiracles in phlebotomine sandfly larvae.
AB - The morphology and ultrastructure of the larval spiracle system of three
phlebotomine sandfly species, Phlebotomus perniciosus, P. perfiliewi and P.
papatasi, were examined by scanning (SEM) and transmission (TEM) electron
microscopy and by confocal scanning laser microscopy (CSLM). During larval
development, thoracic and abdominal spiracles show considerable modifications. In
fourth instar larvae, the spiracles consist of a plate with a sclerotized central
portion and a peripheral circle of papillae. The latter is distinctive in the
larvae of P. papatasi, which are readily distinguished from the other species.
Opening clefts across the papillae communicate with an internal chamber that
encircles an electrondense plug. Many cylindrical projections cross the chamber,
uniting the central plug with the larval body, forming an air filter. Spiracular
development in successive larval instars has both a taxonomic and adaptive value.
PMID- 10194757
TI - Membrane feeding Glossina morsitans centralis on livestock blood and its effect
on the tsetse susceptibility to pathogenic trypanosome infections.
PMID- 10194758
TI - Visualizing protein-protein interactions in the nucleus of the living cell.
PMID- 10194759
TI - Identification of a novel prohormone sorting signal-binding site on
carboxypeptidase E, a regulated secretory pathway-sorting receptor.
AB - Sorting of the prohormone POMC to the regulated secretory pathway necessitates
the binding of a sorting signal to a sorting receptor, identified as membrane
carboxypeptidase E (CPE). The sorting signal, located at the N terminus of POMC
consists of two acidic (Asp10, Glu14) and two hydrophobic (Leu11, Leu18) residues
exposed on the surface of an amphipathic loop. In this study, molecular modeling
of CPE predicted that the acidic residues in the POMC-sorting signal bind
specifically to two basic residues, Arg255 and Lys260, present in a loop unique
to CPE, compared with other carboxypeptidases. To test the model, these two
residues on CPE were mutated to Ser or Ala, followed by baculovirus expression of
the mutant CPEs in Sf9 cells. Sf9 cell membranes containing CPE mutants with
either Arg255 or Lys260, or both residues substituted, showed no binding of
[125I]N-POMC1-26 (which contains the POMC-sorting signal motif), proinsulin, or
proenkephalin. In contrast, substitution of an Arg147 to Ala147 at a substrate
binding site, Arg259 to Ala259 and Ser202 to Pro202, in CPE did not affect the
level of [125I]N-POMC1-26 binding when compared with-wild type CPE. Furthermore,
mutation of the POMC-sorting signal motif (Asp10, Leu11, Glu14, Leu18) eliminated
binding to wild-type CPE. These results indicate that the sorting signal of POMC,
proinsulin, and proenkephalin specifically interacts with Arg255 and Lys260 at a
novel binding site, independent of the active site on CPE.
PMID- 10194760
TI - Alternative splicing of vascular endothelial growth factor (VEGF)-R1 (FLT-1) pre
mRNA is important for the regulation of VEGF activity.
AB - Angiogenesis is essential for normal mammalian development and is controlled by
the local balance of pro- and antiangiogenic factors. Here we describe a novel
mouse cDNA sequence encoding sFLT-1 that is a potent antagonist to vascular
endothelial growth factor (VEGF) and show for the first time its in vivo
production. In situ hybridization and Northern blot analysis with probes specific
for sFLT-1 or FLT-1 showed that the relative abundance of their mRNAs changed
markedly in spongiotrophoblast cells in the placenta as gestation progressed. On
day 11 of pregnancy, sFLT-1 mRNA was undetectable but FLT-1 readily apparent, and
by day 17 sFLT-1 mRNA was abundant but FLT-1 barely detectable. sFLT-1 was
identified in conditioned medium of cultured placenta from day 17 pregnant mice
and likely to be present in the circulation, as there is a substantial increase
of VEGF-binding activity in the serum from day 13 of pregnancy, which coincides
with the abundant sFLT-1 expression in placenta. Expression of sFLT-1 was also
observed in adult lung, kidney, liver, and uterus. These data suggest a novel
mechanism of regulation of angiogenesis by alternative splicing of FLT-1 pre
mRNA. Treatment of pregnant mice with exogenous VEGF from day 9 to 17 of
pregnancy, which alters the ratio of VEGF to sFLT-1, resulted in an increase in
the number of resorption sites and fibrin deposition in the placenta of ongoing
pregnancies. These findings have important implications for understanding
placental function and may be relevant in a range of disease states.
PMID- 10194761
TI - Cyclic adenosine-3',5'-monophosphate-mediated activation of a glutamine
synthetase composite glucocorticoid response element.
AB - The glutamate synthetase gene (GS) contains a composite glucocorticoid response
element (cGRE) comprised of a GRE and an adjacent element with features of both a
cAMP-response element (CRE) and a 12-O-tetradecanoylphorbol 13-acetate (TPA)
response element (TRE). The CRE/TRE element of the cGRE contributed to two modes
of transcriptional activation: 1) enhancement of the response to cortisol and 2)
a synergistic response to cortisol and increased cAMP. COS-7 cells transfected
with a cGRE-luciferase construct show minimal expression under basal conditions
or forskolin treatment. After cortisol treatment, luciferase activity from the
cGRE is enhanced 4- to 8-fold greater than the GRE portion of the cGRE or a GRE
from the tyrosine aminotransferase gene. Treatment with both forskolin and
cortisol produced a 2- to 4-fold synergistic response over cortisol alone.
Synergy is also seen with 8-bromo-cAMP, is specific for the cGRE, and occurs in a
number of established cell lines. Elimination of the GRE or CRE/TRE reduces the
synergy by 70-100%. Altering the CRE/TRE to GRE spacing changed both enhancement
and synergy. Moving the elements 3 bp closer or extending 15 bp reduced
enhancement. Synergy was markedly reduced when elements were one half of a
helical turn out of phase. Western blots verified that CREB (cAMP-responsive
binding protein) and ATF-1 (activating transcription factor-1) binds to the cGRE
sequence. A specific dominant negative inhibitor of the CREB family, A-CREB,
reduced synergy by 50%. These results suggest that the GS cGRE can potentially
integrate signaling from both the cAMP and glucocorticoid receptor transduction
pathways and that CREB/ATF-1 may play an important role in this process.
PMID- 10194762
TI - Extracellular signal-regulated kinase (ERK) interacts with signal transducer and
activator of transcription (STAT) 5a.
AB - Serine phosphorylation of signal transducers and activators of transcription
(STAT) 1 and 3 modulates their DNA-binding capacity and/or transcriptional
activity. Earlier we suggested that STAT5a functional capacity could be
influenced by the mitogen-activated protein kinase (MAPK) pathway. In the present
study, we have analyzed the interactions between STAT5a and the MAPKs,
extracellular signal-regulated kinases ERK1 and ERK2. GH treatment of Chinese
hamster ovary cells stably transfected with the GH receptor (CHOA cells) led to
rapid and transient activation of both STAT5a and ERK1 and ERK2. Pretreatment of
cells with colchicine, which inhibits tubulin polymerization, did not inhibit
STAT5a translocation to the nucleus and ERK1/2 activation. In vitro precipitation
with a glutathione-S-transferase-fusion protein containing the C-terminal
transactivation domain of STAT5a showed GH-regulated association of ERK1/2 with
the fusion protein, while this was not seen when serine 780 in STAT5a was changed
to alanine. In vitro phosphorylation of the glutathione-S-transferase-fusion
proteins using active ERK only worked when the fusion protein contained wild-type
STAT5a sequence. The same experiment, performed with full-length wild-type STAT5a
and the corresponding S780A mutant, showed that serine 780 is the only substrate
in full-length STAT5a for active ERK. In coimmunoprecipitation experiments,
larger amounts of STAT5a-ERK1/2 complexes were detected in cytosol from untreated
CHOA cells than in cytosol from GH-treated cells, suggesting the presence of
preformed STAT5a-ERK1/2 complexes in unstimulated cells. Transfection experiments
with COS cells showed that kinase-inactive ERK1 decreased GH stimulation of STAT5
regulated reporter gene expression. These observations show, for the first time,
direct physical interaction between ERK and STAT5a and also clearly identify
serine 780 as a target for ERK. Furthermore, it is also established that serine
phosphorylation of STAT5a transactivation domain, via the MAPK pathway, is a
means of modifying GH-induced transcriptional activation.
PMID- 10194764
TI - Determination of peptide contact points in the human angiotensin II type I
receptor (AT1) with photosensitive analogs of angiotensin II.
AB - To identify ligand-binding domains of Angiotensin II (AngII) type 1 receptor
(AT1), two different radiolabeled photoreactive AngII analogs were prepared by
replacing either the first or the last amino acid of the octapeptide by p-benzoyl
L-phenylalanine (Bpa). High yield, specific labeling of the AT1 receptor was
obtained with the 125I-[Sar1,Bpa8]AngII analog. Digestion of the covalent 125I
[Sar1,Bpa8]AngII-AT1 complex with V8 protease generated two major fragments of
15.8 kDa and 17.8 kDa, as determined by SDS-PAGE. Treatment of the
[Sar1,Bpa8]AngII-AT1 complex with cyanogen bromide produced a major fragment of
7.5 kDa which, upon further digestion with endoproteinase Lys-C, generated a
fragment of 3.6 kDa. Since the 7.5-kDa fragment was sensitive to hydrolysis by 2
nitro-5-thiocyanobenzoic acid, we circumscribed the labeling site of 125I
[Sar1,Bpa8]AngII within amino acids 285 and 295 of the AT1 receptor. When the AT1
receptor was photolabeled with 125I-[Bpa1]AngII, a poor incorporation yield was
obtained. Cleavage of the labeled receptor with endoproteinase Lys-C produced a
glycopeptide of 31 kDa, which upon deglycosylation showed an apparent molecular
mass of 7.5 kDa, delimiting the labeling site of 125I-[Bpa1]AngII within amino
acids 147 and 199 of the AT1 receptor. CNBr digestion of the hAT1 I165M mutant
receptor narrowed down the labeling site to the fragment 166-199. Taken together,
these results indicate that the seventh transmembrane domain of the AT1 receptor
interacts strongly with the C-terminal amino acid of [Sar1, Bpa8]AngII interacts
with the second extracellular loop of the AT1 receptor.
PMID- 10194763
TI - Homologous regulation of the gonadotropin-releasing hormone receptor gene is
partially mediated by protein kinase C activation of an activator protein-1
element.
AB - Homologous regulation of GnRH receptor (GnRHR) gene expression is an established
mechanism for controlling the sensitivity of gonadotropes to GnRH. We have found
that expression of the GnRHR gene in the gonadotrope-derived alpha T3-1 cell line
is mediated by a tripartite enhancer that includes a consensus activator protein
1 (AP-1) element, a binding site for SF-1 (steroidogenic factor-1), and an
element we have termed GRAS (GnRHR-activating sequence). Further, in transgenic
mice, approximately 1900 b.p. of the murine GnRHR gene promoter are sufficient
for tissue-specific expression and GnRH responsiveness. The present studies were
designed to further delineate the molecular mechanisms underlying GnRH regulation
of GnRHR gene expression. Vectors containing 600 bp of the murine GnRHR gene
promoter linked to luciferase (LUC) were transiently transfected into alpha T3-1
cells and exposed to treatments for 4 or 6 h. A GnRH-induced, dose-dependent
increase in LUC expression of the -600 promoter was observed with maximal
induction of LUC noted at 100 nM GnRH. We next tested the ability of GnRH to
stimulate expression of vectors containing mutations in each of the components of
the tripartite enhancer. GnRH responsiveness was lost in vectors containing
mutations in AP-1. Gel mobility shift data revealed binding of fos/jun family
members to the AP-1 element of the murine GnRHR promoter. Treatment with GnRH or
phorbol-12-myristate-13-acetate (PMA) (100 nM), but not forskolin (10 microM),
increased LUC expression, which was blocked by the protein kinase C (PKC)
inhibitor, GF109203X (100 nM), and PKC down-regulation (10 nM PMA for 20 h). In
addition, a specific MEK1/MEK2 inhibitor, PD98059 (60 microM), reduced the GnRH
and PMA responses whereas the L-type voltage-gated calcium channel agonist, +/-
BayK 8644 (5 microM), and antagonist, nimodipine (250 nM), had no effect on GnRH
responsiveness. Furthermore, treatment of alpha T3-1 cells with 100 nM GnRH
stimulated phosphorylation of both p42 and p44 forms of extracellular signal
regulated kinase (ERK), which was completely blocked with 60 microM PD98059. We
suggest that GnRH regulation of the GnRHR gene is partially mediated by an ERK
dependent activation of a canonical AP-1 site located in the proximal promoter of
the GnRHR gene.
PMID- 10194765
TI - Control of action potential-driven calcium influx in GT1 neurons by the
activation status of sodium and calcium channels.
AB - An analysis of the relationship between electrical membrane activity and Ca2+
influx in differentiated GnRH-secreting (GT1) neurons revealed that most cells
exhibited spontaneous, extracellular Ca(2+)-dependent action potentials (APs).
Spiking was initiated by a slow pacemaker depolarization from a baseline
potential between -75 and -50 mV, and AP frequency increased with membrane
depolarization. More hyperpolarized cells fired sharp APs with limited capacity
to promote Ca2+ influx, whereas more depolarized cells fired broad APs with
enhanced capacity for Ca2+ influx. Characterization of the inward currents in GT1
cells revealed the presence of tetrodotoxin-sensitive Na+, Ni(2+)-sensitive T
type Ca2+, and dihydropyridine-sensitive L-type Ca2+ components. The availability
of Na+ and T-type Ca2+ channels was dependent on the baseline potential, which
determined the activation/inactivation status of these channels. Whereas all
three channels were involved in the generation of sharp APs, L-type channels were
solely responsible for the spike depolarization in cells exhibiting broad APs.
Activation of GnRH receptors led to biphasic changes in cytosolic Ca2+
concentration ([Ca2+]i), with an early, extracellular Ca(2+)-independent peak and
a sustained, extracellular Ca(2+)-dependent phase. During the peak [Ca2+]i
response, electrical activity was abolished due to transient hyperpolarization.
This was followed by sustained depolarization of cells and resumption of firing
of increased frequency with a shift from sharp to broad APs. The GnRH-induced
change in firing pattern accounted for about 50% of the elevated Ca2+ influx, the
remainder being independent of spiking. Basal [Ca2+]i was also dependent on Ca2+
influx through AP-driven and voltage-insensitive pathways. Thus, in both resting
and agonist-stimulated GT1 cells, membrane depolarization limits the
participation of Na+ and T-type channels in firing, but facilitates AP-driven
Ca2+ influx.
PMID- 10194766
TI - The phosphoenolpyruvate carboxykinase gene glucocorticoid response unit:
identification of the functional domains of accessory factors HNF3 beta (hepatic
nuclear factor-3 beta) and HNF4 and the necessity of proper alignment of their
cognate binding sites.
AB - Complete induction of hepatic phosphoenolpyruvate carboxykinase (PEPCK) gene
transcription by glucocorticoids requires a complex glucocorticoid response unit
(GRU). The GRU is comprised of two glucocorticoid receptor (GR)-binding sites
(GR1 and GR2) and four accessory factor-binding sites [AF1, AF2, AF3, and cAMP
response element (CRE)] that bind distinct transcription factors. Hepatic nuclear
factor 4 (HNF4) and chicken ovalbumin upstream promoter transcription factor
(COUP-TF) bind to the AF1 element and account for AF1 activity. Members of the
hepatic nuclear factor 3 (HNF3) family bind to the AF2 element and provide AF2
activity. In this report, we show that the functions of AF1 and AF2 are dependent
on their positions in the promoter, since they cannot substitute for each other
nor can they be exchanged without a reduction in the response to glucocorticoids.
We also identified the domains of HNF4 and HNF3 beta that are required for the
AF1 and AF2 activities, respectively. The carboxy-terminal transactivation domain
of HNF4 (amino acids 128-374) confers most of the AF1 activity, while the
carboxyterminal transactivation domain of HNF3 beta (amino acids 361-458)
mediates AF2 activity. These domains of HNF4 and HNF3 beta appear to have
distinct roles in the response to glucocorticoids, as there are unique structural
requirements for each, as judged by the failure of most other classes of
transactivation domains to serve as accessory factors. These results suggest that
the regulation of the PEPCK gene by glucocorticoids requires specific
interactions between GR, accessory factors, and coactivators, and that the
transactivation domains of AF1 and AF2 are of fundamental importance in the
assembly of this multiprotein complex.
PMID- 10194767
TI - Ternary complex factors Elk-1 and Sap-1a mediate growth hormone-induced
transcription of egr-1 (early growth response factor-1) in 3T3-F442A
preadipocytes.
AB - In our search for transcription factors induced by GH, we have analyzed immediate
early gene activation in a model of GH-dependent differentiation. Here we
describe the activation of early growth response factor-1 (egr-1) in GH
stimulated 3T3-F442A preadipocytes and the transcription factors responsible for
its transactivation. Binding activity of egr-1 in electrophoretic mobility shift
assay (EMSA) increased transiently 1 h after GH stimulation, accompanied by a
concomitant increase in egr-1 mRNA. egr-1 induction appeared not to be related to
proliferation since it was amplified in quiescent preadipocytes at a time when
cells were refractive to GH-stimulated DNA synthesis. Truncations of the proximal
1 kb of the egr-1 promoter revealed that a 374-bp region (-624 to -250)
contributes about 80% of GH inducibility in 3T3-F442A cells and approximately 90%
inducibility in CHO-K1 cells. This region contains three juxtaposed SRE (serum
response element)/Ets site pairs known to be important for egr-1 activity in
response to exogenous stimuli. Site-specific mutations of individual SRE and Ets
sites within this region each reduced GH inducibility of the promoter. Use of
these site-specific mutations in EMSA showed that disruption of either Ets or SRE
sites abrogated ternary complex formation at the composite sites. DNA binding of
ternary complexes, but not binary complexes, in EMSA was rapidly and transiently
increased by GH. EMSA supershifts indicated these ternary complexes contained
serum response factor (SRF) and the Ets factors Elk-1 and Sap-1a. Coexpression of
Sap-1a and Elk-1 resulted in a marked increase in GH induction of egr-1 promoter
activity, although transfection with expression vectors for either Ets factor
alone did not significantly enhance the GH response. We conclude that GH
stimulates transcription of egr-1 primarily through activation of these Ets
factors at multiple sites on the promoter and that stabilization of ternary
complexes with SRF at these sites maximizes this response.
PMID- 10194768
TI - HMG-1 stimulates estrogen response element binding by estrogen receptor from
stably transfected HeLa cells.
AB - Estrogen receptor (ER) toxicity has hampered the development of vertebrate cell
lines stably expressing substantial levels of recombinant wild-type ER. To
isolate clonal lines of HeLa cells stably expressing epitope-tagged ER, we used a
construction encoding a single bicistronic mRNA, in which FLAG-epitope-tagged
human ER alpha (fER) was translated from a 5'-translation initiation site and
fused to the neomycin resistance gene, which was translated from an internal
ribosome entry site. One stable HeLa-ER-positive cell line (HeLa-ER1) produces
1,300,000 molecules of fER/cell (approximately 20-fold more ER than MCF-7 cells).
The HeLa fER is biologically active in vivo, as judged by rapid death of the
cells in the presence of either 17 beta-estradiol or trans-hydroxytamoxifen and
the ability of the cell line to activate a transfected estrogen response element
(ERE)-containing reporter gene. The FLAG-tagged ER was purified to near
homogeneity in a single step by immunoaffinity chromatography with anti-FLAG
monoclonal antibody. Purified fER exhibited a distribution constant (KD) for 17
beta-estradiol of 0.45 nM. Purified HeLa fER and HeLa fER in crude nuclear
extracts exhibit similar KD values for the ERE (0.8 nM and 1 nM, respectively),
which are approximately 10 times lower than the KD of 10 nM we determined for
purified ER expressed using the baculovirus system. HMG-1 strongly stimulated
binding of both crude and purified HeLa fER to the ERE (KD of 0.25 nM). In
transfected HeLa cells, HMG-1 exhibited a dose-dependent stimulation of 17 beta
estradiol-dependent transactivation. At high levels of transfected HMG-1
expression plasmid, transactivation by ER became partially ligand-independent,
and transactivation by trans-hydroxytamoxifen was increased by more than 25-fold.
These data describe a system in which ER, stably expressed in HeLa cells and
easily purified, exhibits extremely high affinity for the ERE, and suggest that
intracellular levels of HMG-1 may be limiting for ER action.
PMID- 10194769
TI - Expression cloning and characterization of PREB (prolactin regulatory element
binding), a novel WD motif DNA-binding protein with a capacity to regulate
prolactin promoter activity.
AB - Previous studies have implied that a transcription factor(s) other than Pit-1 is
involved in homeostatic regulation of PRL promoter activity via Pit-1-binding
elements. One such element, 1P, was employed to clone from a rat pituitary cDNA
expression library a novel 417-amino acid WD protein, designated PREB (PRL
regulatory element binding) protein. PREB contains two PQ-rich potential
transactivation domains, but no apparent DNA-binding motif, and exhibits sequence
specific binding to site 1P, to a site nonidentical to that for Pit-1. The PREB
gene (or a related gene) is conserved, as an apparently single copy, in rat,
human, fly, and yeast. A single approximately 1.9-kb PREB transcript accumulates
in GH3 rat pituitary cells, to levels similar to Pit-1 mRNA. PREB transcripts
were detected in all human tissues examined, but the observation of tissue
specific multiple transcript patterns suggests the possibility of tissue-specific
alternative splicing. RT-PCR analysis of human brain tumor RNA samples suggested
region-specific expression of PREB transcripts in brain. Western and
immunocytochemical analysis implied that PREB accumulates specifically in GH3
cell nuclei. Transient transfection employing PREB-negative C6 rat glial cells
showed that PREB is as active as, and additive with, Pit-1 in transactivation of
a PRL promoter construct, and that PREB, but not Pit-1, can mediate
transcriptional activation by protein kinase A (PKA). Expression in GH3 cells of
a GAL4-PREB fusion protein both strongly transactivated a 5XGAL indicator
construct and yielded a further stimulation of expression of this construct by
coexpressed PKA, implying that PREB can mediate both basal and PKA-stimulated
transcriptional responses in pituitary cells. These observations imply that PREB
will prove to play a significant transcriptional regulatory role, both in the
pituitary and in other organs in which transcripts of its gene are expressed.
PMID- 10194770
TI - Spinal cord pathology and viral burden in homosexuals and drug users with AIDS.
AB - Unless treated with effective antiretroviral therapy many AIDS patients develop a
characteristic vacuolar myelopathy of the spinal cord associated with moderate
clinical disability. Opinion is divided as to whether vacuolar myelopathy is
causally linked to HIV myelitis. To investigate this further, spinal cord
pathology was assessed in 41 drug users, 33 homosexual men and 16 other patients,
all with AIDS. Previous work has shown that HIV encephalitis is more common in
Edinburgh drug users than in homosexual men. In the present study HIV myelitis
(10% overall) was more common in drug users (17%) than in homosexual men (3%) (P
= 0.05), whereas the incidence of opportunistic infections (7% v. 9%) and
lymphomas (2% v. 6%) was comparable in the two groups, but with a slight trend in
the reverse direction, reflecting similar findings in the brain. However,
moderate or severe vacuolar myelopathy was equally represented in both groups
(20% of drug users and 21% of homosexual men). The HIV proviral load, assessed by
polymerase chain reaction in frozen samples of thoracic spinal cord in 37 cases,
correlated closely with the presence of giant cells and/or with
immunocytochemical evidence of productive HIV infection. In 13 cases, the
proviral load was measured in cervical, thoracic and lumbar samples and proved to
be uniformly high or low in individual cases. This study provides no evidence for
direct involvement of HIV, cytomegalovirus, papovavirus or human foamy virus in
the pathogenesis of vacuolar myelopathy.
PMID- 10194771
TI - Progressive dendritic pathology in cynomolgus macaques infected with simian
immunodeficiency virus.
AB - Neuronal pathology in acquired immunodeficiency syndrome (AIDS) is of interest in
relation to cognitive impairment in AIDS patients and from the broader
perspective of the pathogenesis of neurodegeneration. Cortical dendritic spine
loss has been described in patients with AIDS and the aim of this study was to
test the hypothesis that similar pathology is present in cynomolgus macaques
infected with simian immunodeficiency virus (SIV). These animals develop an AIDS
like illness, but multinucleated giant cell encephalitis is not a feature and CNS
virus load is found to be very low. Four animals infected for 2.5-3 months and
four infected for 2-3 years were compared with four controls. The Golgi-Cox
technique was employed to demonstrate dendritic morphology in the frontal cortex
and the diameter of apical dendrites, dendritic spine density and dendritic spine
lengths were measured in layer V pyramidal cells. Immunohistochemistry for
microtubule-associated protein-2 (MAP-2), MHC class II and glial fibrillary
acidic protein (GFAP) was also performed. In infected animals there was
progressive spine loss and atrophy of remaining spines with loss of MAP-2
immunoreactivity at late time points. No parallel increase in GFAP immunostaining
or MHC-class II expression in microglial cells was seen. We conclude that
progressive neuronal dendritic pathology is a feature of SIVmac251 infection of
cynomolgus macaques and is apparent relatively early in disease. Furthermore,
dendritic abnormalities occur in the absence of either multinucleated giant cell
pathology or substantial CNS virus load.
PMID- 10194772
TI - The acute inflammatory response in CNS following injection of prion brain
homogenate or normal brain homogenate.
AB - The neuropathological hallmarks of end-stage prion disease are vacuolation,
neuronal loss, astrocytosis and deposition of PrPSc amyloid. We have also shown
that there is an inflammatory response in the brains of scrapie-affected mice
from 8 weeks post-injection. In this study we have investigated the acute CNS
response to the intracerebral injection of scrapie-affected brain homogenate. The
ME7 strain of scrapie (Neuropathogenesis Unit, Edinburgh) was used, and control
mice were injected with brain homogenate derived from normal C57BL/6 J mice. One
microlitre of 10% w/v ME7 (n = 33) and normal brain homogenate (n = 28) was
injected stereotaxically into the right dorsal hippocampus. Cryostat sections of
brains taken at 1, 2, 5, 7, 14 and 28 days post-injection were examined
histologically for neuronal loss, and immunocytochemically to study the
inflammatory response. This study shows that ME7 is not acutely neurotoxic in
vivo. There is also no difference (ANOVA) in the inflammatory response, which
peaked between 2 and 5 days and resolved by 4 weeks after intracerebral injection
of either ME7 or normal brain homogenate. The well circumscribed inflammatory
response seen previously at 8 weeks is therefore a consequence of a disease
process rather than a surgical artefact. This disease process may be related to a
localized accumulation of PrPSc sufficient to stimulate an inflammatory response
which in turn may contribute to neuronal loss. The role of the inflammatory
response in chronic neurodegeneration can be usefully studied using this mouse
model of prion disease, and this will undoubtedly shed light on the pathogenic
mechanisms underlying other chronic neurodegenerative diseases.
PMID- 10194773
TI - Histology and platinum content of sensory ganglia and sural nerves in patients
treated with cisplatin and carboplatin: an autopsy study.
AB - Cisplatin is a valuable antineoplastic drug which as a dose-limiting side-effect
causes sensory neuropathy, and which therefore is often combined with less
neurotoxic carboplatin. It has not been possible to reproduce cisplatin
neuropathy in experimental animals, and the neurotoxic mechanism in man is
disputed. We investigated post-mortem material from 12 patients and 15 control
subjects. Half of the fibres with diameters of > or = 9 microns, or more than 15%
of all fibres (P < 0.02), had disappeared in the sural nerves of patients. Signs
of axonal regeneration were lacking. The dorsal root ganglia D12 and L2 of some
but not of all patients contained necrotic neurons and nodules of Nageotte. The
mean volume of the somata was reduced by 18% (P < 0.03). A relation between
cumulated doses, treatment free interval and changes in nerve or ganglia was not
found. The platinum content was high in all tissues except in the spinal cord
when the patient had died shortly after treatment, and it decreased with
increasing interval, least so in liver, sensory ganglia and sural nerves. The
results support the hypothesis that cisplatin neuropathy is a neuroneopathy
rather than a dying-back axonopathy.
PMID- 10194774
TI - A comparison of manual and semi-automated methods in the assessment of axonal
injury.
AB - Diffuse axonal injury (DAI) in the central nervous system is a common cause of
post-traumatic coma and may result in varying degrees of disability up to and
including the vegetative state. Experimental studies in man and animals have
previously relied upon semi-quantitative grading systems for determining the
relationship between the extent of DAI and the clinical features of patients.
Using beta-amyloid precursor protein immunocytochemistry for the detection of DAI
in sections of corpus callosum from 15 cases of fatal head injury, we have
developed a quantitative image analysis technique for the assessment of axonal
injury. This new method is objective and reproducible and should allow better
correlation with biomechanical, radiological, and clinical parameters to increase
our understanding of DAI.
PMID- 10194775
TI - No evidence for astrogliosis in brains of schizophrenic patients. A post-mortem
study.
AB - Schizophrenia is clinically and neuropsychologically characterized by severe
cognitive and functional impairment suggesting the presence of a
neurodegenerative process in the brains of affected individuals. A variety of
neuroanatomical changes have been described such as loss and disorientation of
neurons in grey and white matter and cortical atrophy. However, the
neuropathological basis for schizophrenia is still unclear. In the present study
we monitored the density of GFAP-positive astrocytes in brains of 33
schizophrenic patients and 26 healthy controls. Both grey matter (entorhinal
cortex and subiculum) and white matter (premotor cortex, subventricular zone of
the third ventricle and next to inferior horn) structures were measured
bilaterally. The overall finding was that there is no evidence for increased
astrogliosis in brains of schizophrenic patients vs healthy controls. Therefore,
degeneration is unlikely to be the main neuropathological mechanism in
schizophrenic brains.
PMID- 10194776
TI - Expression of extracellular matrix degrading enzymes during migration of
xenografted brain cells.
AB - Proteolytic enzymes, postulated to create an avenue for cell migration by
digestion of host extracellular matrix molecules, have been implicated in
neoplastic glial cell migration. A similar process is likely to occur in the
developing brain. Fetal rabbit brain fragments transplanted into the striatum of
the neonatal Shiverer mouse give rise to cells which migrate from the graft site
and differentiate into astrocytes and oligodendrocytes. Proteinase expression by
transplanted brain cells was studied using immunohistochemistry and in situ
hybridization. Immature donor cells expressed the mRNAs for matrix
metalloproteinases (MMP) 1 (collagenase) and 3 (stromelysin). Northern blot
analysis of rabbit brain showed that MMP-1 in particular is expressed in the
immature rabbit cerebrum and down-regulated during maturation. Immature donor
cells exhibited immunoreactivity for urokinase plasminogen activator. However,
immunoreactivity was also present in maturing neurons. Donor and host astroglia
in the vicinity of grafts were immunoreactive for MMP-2 and tissue-type
plasminogen activator. This expression may represent a reactive phenomenon, not
specifically related to cell migration, by mature astrocytes. Based upon our
findings, MMP-1 appears to be a candidate for involvement in migration of
immature brain cells in the cerebrum.
PMID- 10194777
TI - Expression of angiogenic factors in rabbit spinal cord after transient ischaemia.
AB - It is known that angiogenic factors are induced in brain by ischaemia, and new
vessel formation is correlated with better prognosis in patients of stroke.
However, the role of angiogenesis and expression of angiogenic factors in spinal
cord ischaemia is uncertain. We here investigated expression of three highly
potent angiogenic peptides, i.e. basic fibroblast growth factor (bFGF), vascular
endothelial growth factor (VEGF), and hepatocyte growth factor (HGF) in the
rabbit spinal cord after transient ischaemia, by Western blot and
immunohistochemical analysis. Western blot analysis revealed that bFGF was
induced at 8 h after transient ischaemia and decreased thereafter. Immunoreactive
VEGF was also induced at 8 h, and it disappeared thereafter. HGF was not detected
in the spinal cord with sham-operation or ischaemic injury. By
immunohistochemical analysis, bFGF was weakly expressed in only a few small
interneurons in sham-operated spinal cords. However, it was induced to a marked
degree in motor neurons and interneurons of the anterior horn at 8 h after
reperfusion. It was also induced in small neurons of the posterior horn. The
expression in the anterior horn decayed thereafter though it lasted until 7 d in
the posterior horn. VEGF was not expressed in sham-operated spinal cords, but the
expression was induced in large motor neurons and interneurons at 8 h with marked
reduction at 1 d. In contrast, HGF was not expressed in the spinal cord with sham
operation or ischaemic injury. These factors are known to play pivotal roles in
angiogenesis, regulation of blood flow, and protection of endothelial cells.
Through induction of these angiogenic peptides, protection of vascular
endothelial cells and improvement of regional blood flow might be occurring in
the spinal cord after ischaemia.
PMID- 10194778
TI - Infantile HIV encephalopathy associated with cerebral and cerebellar
telangiectases.
AB - We describe a paediatric case of HIV encephalopathy associated with cerebral and
cerebellar telangiectases. Although immunohistochemistry failed to show HIV in
the walls of dilated blood vessels, or in their vicinity, brain capillary
telangiectases might be an additional complication indirectly related to
paediatric HIV infection.
PMID- 10194779
TI - Accuracy in breast imaging requires multiple views and an integrated approach.
PMID- 10194780
TI - Complications of cancer therapy in children: a radiologist's guide.
AB - As advances in cancer therapy improve the prognosis of patients with childhood
malignancies, awareness of the consequences of treatment methods assumes
increasing importance. All cancer treatment modalities are associated with toxic
effects, and the spectrum of therapy-induced complications involves all organ
systems. Radiologists have a pivotal role in detecting these sequelae, which can
be categorized by the affected organ system and by whether they occur (a) at
diagnosis or during initial therapy or (b) after the completion of treatment. The
first group consists of oncologic emergencies, infectious complications, and
irritant effects. Oncologic emergencies can be further categorized as space
occupying lesions (e.g., superior vena cava syndrome or spinal cord compression),
vascular abnormalities (e.g., hyperleukocytosis, anemia, coagulopathy), and
metabolic emergencies (e.g., tumor lysis syndrome). Common complications
developing after completion of treatment include leukoencephalopathy and
neurocognitive defects; cataract formation; cardiomyopathy and congestive heart
failure; hepatic dysfunction, fibrosis, and cirrhosis; radiation enteritis; renal
dysfunction or failure; scoliosis and short stature; hypothyroidism; gonadal
dysfunction; graft-versus-host disease; and development of secondary
malignancies. Physician awareness of these complications will permit more
effective patient surveillance, which may afford patients the opportunity for
earlier intervention in these situations and improved quality of life.
PMID- 10194782
TI - Imaging of cardiac transplantation complications.
AB - Common complications of cardiac transplantation include infection, rejection,
accelerated coronary artery atherosclerosis, and lymphoproliferative disease. The
authors reviewed radiographic and computed tomographic (CT) features of cardiac
transplantation and its complications in a series of 232 patients (with 89
complications and 49 deaths). Normal postoperative findings in the first few
weeks after surgery included enlarged cardiac silhouette, pneumomediastinum,
pneumothorax, pneumopericardium, subcutaneous emphysema, and mediastinal
widening. Infection was the most common complication, with pneumonia being the
leading infectious condition (28 cases, with Aspergillus [n = 11] and
cytomegalovirus [n = 10] being the most common pathogens) and the cause of death
in seven cases. Although many cases of pulmonary infections occur in the first 3
4 months after surgery, in this series several cases developed up to 3 years
afterward. Radiographic signs of acute rejection were nonspecific in the eight
patients affected who died, and endomyocardial biopsy was used to confirm the
suspected diagnosis. Accelerated atherosclerosis occurred in 13 patients between
10 months and 6.5 years after transplantation and led to death in eight.
Lymphoproliferative disorders, which range from benign lymphoid hyperplasia to
malignant lymphoma and which are the third leading cause of death beyond the
immediate perioperative period in heart transplant recipients, developed in four
patients who later died. Other complications related to endomyocardial biopsy and
cardiothoracic surgery (i.e., pneumothorax, hemothorax, pneumomediastinum,
mediastinitis, aortic dissection, aortic pseudoaneurysm, and pulmonary embolism)
occurred in 31 cases and were diagnosed with radiography and CT.
PMID- 10194781
TI - Intussusception in children: current concepts in diagnosis and enema reduction.
AB - Intussusception cannot be reliably ruled out with clinical examination and plain
radiography. However, a contrast material enema study and ultrasonography (US)
allow definitive diagnosis of intussusception. The components of an
intussusception produce characteristic appearances on US scans. These appearances
include the multiple concentric ring sign and crescent-in-doughnut sign on axial
scans and the sandwich sign and hayfork sign on longitudinal scans. Indicators of
ischemia and irreducibility are trapped fluid at US and absence of blood flow at
Doppler imaging. The aim of enema therapy is to reduce the greatest number of
intussusceptions without producing perforation. Barium, water-soluble contrast
media, water, electrolyte solutions, or air may be used with radiographic or US
guidance. The differences in reduction and perforation rates between the various
types of enemas are probably due more to perforations that occurred before enema
therapy and the pressure exerted within the colon than to the contrast material
used. The pressure within the colon is more constant with hydrostatic reduction
than with air reduction; this fact may explain the lower risk of perforation with
hydrostatic reduction. Radiation exposure is lower with air enema therapy than
with barium enema therapy and is absent in US-guided enema therapy.
PMID- 10194784
TI - Chemical shift: the artifact and clinical tool revisited.
AB - The chemical shift phenomenon refers to the signal intensity alterations seen in
magnetic resonance (MR) imaging that result from the inherent differences in the
resonant frequencies of precessing protons. Chemical shift was first recognized
as a misregistration artifact of image data. More recently, however, chemical
shift has been recognized as a useful diagnostic tool. By exploiting inherent
differences in resonant frequencies of lipid and water, fatty elements within
tissue can be confirmed with dedicated chemical shift MR pulse sequences.
Alternatively, the recognition of chemical shift on images obtained with standard
MR pulse sequences may corroborate the diagnosis of lesions with substantial
fatty elements. Chemical shift can aid in the diagnosis of lipid-containing
lesions of the brain (lipoma, dermoid, and teratoma) or the body (adrenal
adenoma, focal fat within the liver, and angiomyolipoma). In addition, chemical
shift can be implemented to accentuate visceral margins (e.g., kidney and liver).
PMID- 10194783
TI - Use of sentinel node lymphoscintigraphy in malignant melanoma.
AB - Lymphoscintigraphy is a sensitive, inexpensive, relatively noninvasive method of
identifying lymphatic drainage patterns and sentinel lymph nodes in patients with
malignant melanoma. Lymphoscintigraphy with filtered technetium-99m sulfur
colloid allows prompt visualization of the lymphatic system, produces high
quality images, and delivers a low radiation dose to the patient. In addition,
good regional lymph node retention is seen with filtered Tc-99m sulfur colloid,
improving the success rate of intraoperative gamma probe localization. In
combination with surgical localization, lymphoscintigraphy allows preoperative
and intraoperative identification of the sentinel node in patients with
intermediate thickness melanomatous lesions, obviating radical lymph node
dissection in most patients and possibly prolonging their survival. Variables
such as tumor location, type and preparation of radiopharmaceutical, injection
technique, imaging technique, and prior surgical intervention influence the
efficacy of lymphoscintigraphy. Nevertheless, lymphoscintigraphy is recommended
as a cost-effective preoperative procedure in all patients planning to undergo
elective lymph node dissection. Because of the unpredictability of lymphatic
drainage, preoperative scintigraphic findings may lead to changes in surgical
management.
PMID- 10194785
TI - Fat suppression in MR imaging: techniques and pitfalls.
AB - Fat suppression is commonly used in magnetic resonance (MR) imaging to suppress
the signal from adipose tissue or detect adipose tissue. Fat suppression can be
achieved with three methods: fat saturation, inversion-recovery imaging, and
opposed-phase imaging. Selection of a fat suppression technique should depend on
the purpose of the fat suppression (contrast enhancement vs tissue
characterization) and the amount of fat in the tissue being studied. Fat
saturation is recommended for suppression of signal from large amounts of fat and
reliable acquisition of contrast material-enhanced images. The main drawbacks of
this technique are sensitivity to magnetic field nonuniformity, misregistration
artifacts, and unreliability when used with low-field-strength magnets. Inversion
recovery imaging allows homogeneous and global fat suppression and can be used
with low-field-strength magnets. However, this technique is not specific for fat,
and the signal intensity of tissue with a long T1 and tissue with a short T1 may
be ambiguous. Opposed-phase imaging is a fast and readily available technique.
This method is recommended for demonstration of lesions that contain small
amounts of fat. The main drawback of opposed-phase imaging is unreliability in
the detection of small tumors embedded in fatty tissue.
PMID- 10194786
TI - Endoluminal MR imaging of the rectum and anus: technique, applications, and
pitfalls.
AB - Anorectal diseases (e.g., fecal incontinence, perianal and anovaginal fistulas,
anorectal tumors) require imaging for proper case management. Endoluminal
magnetic resonance (MR) imaging has become an important part of diagnostic work
up in such cases. Optimal endoluminal MR imaging requires careful attention to
patient preparation, imaging protocols, and potential pitfalls in interpretation.
Comfortable positioning and the use of an antiperistaltic drug are vital for
adequate patient preparation. Selected sequences and imaging planes are used in
imaging protocols tailored for specific diseases. In fecal incontinence, three
dimensional sequences allow detailed demonstration of the anal anatomy and
related defects. In perianal and anovaginal fistulas, longitudinal imaging planes
help determine the superior extent of the abnormality. In anorectal tumors, T1
weighted turbo spin-echo MR imaging can help detect extension into the perirectal
fat and T2-weighted turbo spin-echo MR imaging is used to optimize contrast
between tumor and the rectal wall. Off-axis and radial imaging planes are used in
all anorectal diseases to minimize partial volume effects. Potential pitfalls
include various parts of the normal anal anatomy mimicking sphincter defects,
veins and hemorrhoids mimicking fistulas and abscesses, and overhanging tumor
mimicking more extensive tumor. Adequate patient preparation combined with proper
technique and a knowledge of potential pitfalls will allow optimal endoluminal MR
imaging of the rectum and anus.
PMID- 10194787
TI - Chemoembolization of hepatic neoplasms: safety, complications, and when to worry.
AB - Chemoembolization of the liver for unresectable malignancy, although
controversial, is being used with increasing frequency. Chemoembolization can be
difficult, and there is great potential for causing complications. There are also
findings after chemoembolization, particularly on computed tomographic scans,
that may appear to indicate complications but are common and of no concern.
Chemoembolization requires an understanding of the congenital and acquired
variations of arterial anatomy that may be seen supplying the liver. Assessment
of the patency of the portal vein is also required. An abnormal portal vein
demands significant changes in technique to allow safe chemoembolization. Partial
or complete occlusion of the portal vein is associated with significantly
decreased survival but does not prevent a worthwhile response to
chemoembolization and is not an absolute contraindication. The presence of
chemoembolization material in the gallbladder is not uncommon; with the technique
used by the authors, the chemoembolization material infrequently causes
cholecystitis or gallbladder infarction. Extrahepatic chemoembolization material
is commonly seen in other organs but usually does not cause problems, presumably
because the dose deposited outside the liver is small compared with the dose
delivered to the liver. Other complications include pseudocirrhosis, liver
infarction and abscess formation, carcinoid crisis, hepatorenal syndrome, and
liver rupture.
PMID- 10194788
TI - Diagnostic pitfalls of MR cholangiopancreatography in the evaluation of the
biliary tract and gallbladder.
AB - Magnetic resonance (MR) cholangiopancreatography is a noninvasive imaging
technique that has proved accurate in the diagnosis of biliary obstruction.
However, various diagnostic pitfalls have been reported with MR
cholangiopancreatography that were not encountered previously at conventional
biliary imaging. These pitfalls may simulate or mask various pathologic
conditions of the extrahepatic bile duct or main pancreatic duct and may be
caused by a variety of factors. Because of its postprocessing nature, maximum
intensity-projection reconstruction may mask a small gallstone if the stone is
surrounded by hyperintense bile and may cause false ductal disconnection or
duplication when a breath hold is not performed perfectly. Extraductal factors
(e.g., metallic surgical clips, intravascular metallic coils, gas in the stomach
or duodenum) can cause signal loss in the adjacent part of the extrahepatic bile
duct, which may in turn lead to a false-positive diagnosis of ductal narrowing or
obstruction. Normal vascular structures including the right hepatic and
gastroduodenal arteries can cause pseudo-obstruction of the extrahepatic bile
duct by pulsatile compression. Intraductal factors (e.g., gas, hemorrhage,
debris, iodinated contrast material) reduce the signal intensity of the bile,
which may result in pseudo-obstruction, false filling defects, or a nonvisualized
gallbladder or bile duct. Knowledge of the existence and high prevalence of these
diagnostic pitfalls should help prevent misinterpretation of MR
cholangiopancreatograms.
PMID- 10194789
TI - CT and MR imaging of benign hepatic and biliary tumors.
AB - Benign hepatic and biliary tumors can present a difficult diagnostic challenge.
Spiral computed tomography (CT) and magnetic resonance (MR) imaging are useful in
the detection and characterization of these tumors. Imaging characteristics of
lesions such as hepatic cyst, hemangioma, focal nodular hyperplasia (FNH), and
hepatic adenoma are well known. Hepatic cysts demonstrate water attenuation at
CT, are isointense relative to water at MR imaging, and do not enhance after
intravenous administration of contrast material. Hemangiomas demonstrate
characteristic nodular peripheral enhancement on early-phase images with
subsequent fill-in centrally at both modalities. FNH classically demonstrates
intense early enhancement with washout on delayed images. Although hepatic
adenoma can also demonstrate intense early enhancement, it has a tendency to
bleed and thus often appears more heterogeneous than FNH due to hemorrhage.
Benign hepatic tumors that are less well described in the imaging literature
include hepatic lipoma or angiomyolipoma, infantile hemangioendothelioma, and
mesenchymal hamartoma. Hepatic lipoma has fat attenuation at CT, is isointense
relative to fat at MR imaging, and does not enhance after intravenous
administration of contrast material. Hepatic angiomyolipomas contain a variable
amount of soft tissue in addition to fat and may therefore demonstrate
enhancement at both modalities. The CT and MR imaging appearances of infantile
hemangioma are similar to those of adult hemangioma. Infantile
hemangioendothelioma occurs in infants under 6 months of age and is typically a
larger lesion. Mesenchymal hamartoma also occurs in children, and its imaging
appearance depends on the presence of stromal elements and the protein content of
the cyst fluid. Familiarity with these imaging features can help distinguish
particular disease entities.
PMID- 10194790
TI - Fibrolamellar carcinoma of the liver: radiologic-pathologic correlation.
AB - Fibrolamellar carcinoma is a malignant hepatocellular tumor with distinct
clinical and pathologic differences from hepatocellular carcinoma. It differs
from hepatocellular carcinoma in demographics, condition of the affected liver,
tumor markers, and prognosis. Fibrolamellar carcinoma characteristically
manifests as a large hepatic mass in adolescents or young adults (without gender
predominance). Cirrhosis; elevated alpha-fetoprotein levels; and typical risk
factors for hepatocellular carcinoma such as viral hepatitis, alcohol abuse, and
metabolic disease are typically absent. Fibrolamellar carcinoma is characterized
pathologically by cords of tumor cells surrounded by abundant collagenous fibrous
tissue arranged in a parallel or lamellar distribution. Fibrotic lamellae often
coalesce to form a central scar. Fibrolamellar carcinoma characteristically
appears on radiologic images as a lobulated heterogeneous mass with a central
scar in an otherwise normal liver. Radiologic evidence of cirrhosis, vascular
invasion, or multifocal disease--findings typical of hepatocellular carcinoma--is
uncommon in fibrolamellar carcinoma. Imaging features of fibrolamellar carcinoma
overlap with those of other scar-producing lesions including focal nodular
hyperplasia (FNH), hepatocellular adenoma and carcinoma, hemangioma, metastases,
and cholangiocarcinoma. FNH, in particular, may simulate fibrolamellar carcinoma,
since both have similar demographic and clinical characteristics. Because some
believe that radiologic diagnosis of FNH is possible, it is important to
understand the imaging appearance of fibrolamellar carcinoma to avoid
misdiagnosing this malignant tumor as a FNH.
PMID- 10194791
TI - Radiation detectors in nuclear medicine.
AB - Single-photon-emitting or positron-emitting radionuclides employed in nuclear
medicine are detected by using sophisticated imaging devices, whereas simpler
detection devices are used to quantify activity for the following applications:
measuring doses of radiopharmaceuticals, performing radiotracer bioassays, and
monitoring and controlling radiation risk in the clinical environment. Detectors
are categorized in terms of function, the physical state of the transducer, or
the mode of operation. The performance of a detector is described by the
parameters efficiency, energy resolution and discrimination, and dead time. A
detector may be used to detect single events (pulse mode) or to measure the rate
of energy deposition (current mode). Some detectors are operated as simple
counting systems by using a single-channel pulse height analyzer to discriminate
against background or other extraneous events. Other detectors are operated as
spectrometers and use a multichannel analyzer to form an energy spectrum. The
types of detectors encountered in nuclear medicine are gas-filled detectors,
scintillation detectors, and semiconductor detectors. The ionization detector,
Geiger-Muller detector, extremity and area monitor, dose calibrator, well
counter, thyroid uptake probe, Anger scintillation camera, positron emission
tomographic scanner, solid-state personnel dosimeter, and intraoperative probe
are examples of detectors used in clinical nuclear medicine practice.
PMID- 10194792
TI - Quality assurance in mammography: artifact analysis.
AB - Evaluation of mammograms for artifacts is essential for mammographic quality
assurance. A variety of mammographic artifacts (i.e., variations in mammographic
density not caused by true attenuation differences) can occur and can create
pseudolesions or mask true abnormalities. Many artifacts are readily identified,
whereas others present a true diagnostic challenge. Factors that create artifacts
may be related to the processor (eg, static, dirt or excessive developer buildup
on the rollers, excessive roller pressure, damp film, scrapes and scratches,
incomplete fixing, power failure, contaminated developer), the technologist (eg,
improper film handling and loading, improper use of the mammography unit and
related equipment, positioning and darkroom errors), the mammography unit (eg,
failure of the collimation mirror to rotate, grid inhomogeneity, failure of the
reciprocating grid to move, material in the tube housing, compression failure,
improper alignment of the compression paddle with the Bucky tray, defective
compression paddle), or the patient (e.g., motion, superimposed objects or
substances [jewelry, body parts, clothing, hair, implanted medical devices,
foreign bodies, substances on the skin]). Familiarity with the broad range of
artifacts and the measures required to eliminate them is vital. Careful attention
to darkroom cleanliness, care in film handling, regularly scheduled processor
maintenance and chemical replenishment, daily quality assurance activities, and
careful attention to detail during patient positioning and mammography can reduce
or eliminate most mammographic artifacts.
PMID- 10194793
TI - An economical, personal computer-based picture archiving and communication
system.
AB - Taichung Veterans General Hospital has been developing a hospital-wide picture
archiving and communication system (PACS) since 1993. A personal computer-based
environment was implemented to reduce costs (only $2,500 for each view station)
and take advantage of distributed system techniques. Other features of the PACS
are automatic image acquisition, hierarchic storage management, efficient image
transmission, robust fault tolerance, and user-friendly image manipulation. The
system is integrated with the hospital information system so that Chinese
language patient data can be automatically transferred. A four-tier storage
hierarchy and a multipath search strategy are used to improve reliability and
efficiency. Image compression and efficient image transmission techniques
(autorouting and prefetching) are used to reduce the response time. Robust fault
tolerance is achieved with fault-tolerant hardware, image replication, and a
system watchdog. User-friendly image manipulation features include easy
adjustment of the brightness, contrast, or quality of the displayed image;
several windows for image display; and image measurement capability. The PACS
currently supports computed tomography, ultrasound, magnetic resonance imaging,
computed radiography, and digital fluoroscopy; almost all appropriate personal
computers in the hospital can be used as view stations. Users are satisfied with
the quality, reliability, and performance of the system.
PMID- 10194794
TI - Epithelioid hemangioendothelioma of the lower extremity.
PMID- 10194796
TI - Neuroradiology case of the day. Alveolar soft part sarcoma.
PMID- 10194795
TI - General case of the day. Jejunal intussusception caused by an inflammatory
fibroid polyp (IFP).
PMID- 10194797
TI - Gastrointestinal case of the day. Gardner syndrome.
PMID- 10194798
TI - Breast imaging case of the day. Multiple giant fibroadenomas associated with
cyclosporin A therapy.
PMID- 10194799
TI - Pediatric case of the day. Tuberculous osteomyelitis with skull involvement and
epidural abscess.
PMID- 10194800
TI - US case of the day. Large, bilateral angiomyolipomas of the kidneys with tuberous
sclerosis.
PMID- 10194801
TI - Normal digital artery blood flow in antiepileptic drug embryopathy.
PMID- 10194802
TI - Risk factors for heart defects in Down syndrome.
PMID- 10194804
TI - Mechanism of hyperthermia effects on CNS development: rostral gene expression
domains remain, despite severe head truncation; and the hindbrain/otocyst
relationship is altered.
AB - To study the mechanism of hyperthermia on the development of the rostral neural
tube, we used a model in which closely-staged presomite 9.5-day rat embryos were
exposed in culture to 43 degrees C for 13 min, and then cultured further for 12
48 hr. This treatment had little effect on the development of the rest of the
embryo, but resulted in a spectrum of brain defects, the most severe being a lack
of all forebrain and midbrain structures. Whole-mount in situ hybridisation was
used to monitor the expression domains of Otx2, Emx2, Krox20, and hoxb1. These
showed that there were no ectopic expression patterns, for any gene at any stage
examined. Even in those embryos which apparently lacked all forebrain and
midbrain structures, there were expression domains of Otx2 and Emx2 in the most
rostral neural tissue, and these retained their nested dorso-ventral boundaries,
showing that cells fated to form rostral brain were not wholly eliminated. Thus,
heat-induced rostral neural tube truncation is of a quite different mechanism
from the respecification proposed for retinoic acid, despite their very similar
phenotypes. In the hindbrain region of treated embryos, we observed decreased
intensity of Krox20, staining and an abnormal relationship developed between the
position of hoxb1 expression and the otocyst and pharyngeal arches. In the most
extreme cases, this domain was shifted to be more caudal than the rostral edge of
the otocyst, while the otocyst retained its normal position relative to the
pharyngeal arches. We interpret this as a growth imbalance between
neuroepithelium and overlying tissues, perhaps due to a disruption of signals
from the midbrain/hindbrain boundary.
PMID- 10194805
TI - Bisdiamine inhibits extracellular matrix formation and cell proliferation of
atrioventricular mesenchyme from developing chick heart valves.
AB - Abnormalities of the cushion tissues lead to atrioventricular septal defects
(AVSD) and truncus arteriosus (TA). Bisdiamine exposure in the embryo frequently
causes AVSD and TA in the newborn chick, mouse, or rat. We studied the effects of
bisdiamine on mesenchymal cells grown in aggregate culture isolated from the
developing atrioventricular valves of the stage-36 chick embryo. Fibronectin
extracellular matrix formation and cell proliferation in the aggregates were
assessed in various media. Chick serum stimulated the cells to produce an
extracellular matrix and to divide, and the inclusion of bisdiamine inhibited
both responses. If we isolated an extracellular matrix from a monolayer of
mesenchymal cells and added the sonicated matrix to the medium containing serum
and bisdiamine, the matrix incorporated into the aggregates and the cells entered
the mitotic cycle. Our previous work established that cells need to attach to an
intact extracellular matrix to begin cell division. Thus, we suggest that
bisdiamine inhibits the normal formation of the extracellular matrix, leading to
reduced cell proliferation, but it does not affect matrix-cell interaction. The
lack of cushion growth in situ may be the cause of AVSD or TA.
PMID- 10194803
TI - Effect of prenatal gamma irradiation during the late fetal period on the
postnatal development of the mouse.
AB - Pregnant Swiss albino mice were exposed to 0.3, 0.5, 1.0, or 1.5 Gy of gamma
radiation on day 17 of gestation. Sham-exposed controls were examined for
comparison. Exposed mice as well as controls were left to complete gestation and
parturition. Pups were observed up to age 6 weeks; appearance of physiological
markers (pinna detachment, eye opening, fur development, vaginal opening, and
testes descent), postnatal mortality, body weight, body length, head length, head
width, and tail length were recorded. A significant delay in fur development was
observed at 0.3 Gy and in other physiological markers at doses above 0.3 Gy,
while a significant increase in mortality and growth retardation occurred only at
1.0 and 1.5 Gy. Although congenital anomalies such as syndactyly and bent tail
were observed at doses of 0.5-1.5 Gy, only syndactyly showed a statistically
significant increase in frequency. A statistically significant lower body weight
was observed during the first week of postnatal life, but body weights increased
to normal levels by the second week in animals exposed to doses less than 1.0 Gy.
At higher doses, low body weight persisted throughout the postnatal period. Head
length and tail length showed a significant decrease from controls at 0.5-1.5 Gy,
and the effect was evident from birth to age 6 weeks. But a similar effect on
body length and head width was noticed only at 1.0 and 1.5 Gy. These studies
indicate that even in the absence of any major morphological changes, normal
development of physiological landmarks and postnatal growth can be impaired by
fetal irradiation at 17 days p.c. (post coitus). Morphological changes appear to
have a threshold between 0.3-0.5 Gy, while physiological marker effects may occur
with a lower threshold.
PMID- 10194806
TI - Multigeneration reproductive toxicity assessment of 60-Hz magnetic fields using a
continuous breeding protocol in rats.
AB - Male and female reproductive functions have been proposed as possibly sensitive
targets for the biological effects of 60-Hz (power frequency) magnetic fields
(MF). However, experimental data relevant to this hypothesized association are
very limited. In the present study, the "reproductive assessment by continuous
breeding" design was used to identify possible effects of MF exposure on
reproductive performance, fetal development, and early postnatal growth in rats.
Groups of age-matched Sprague-Dawley rats (40 breeding pairs/group) were exposed
continuously (18.5 hr per day) to linearly polarized, transient-free 60-Hz MF at
field strengths of 0 Gauss (G; sham control), 0.02 G, 2.0 G, or 10.0 G. An
additional group of 40 breeding pairs received intermittent (1 hr on/1 hr off)
exposure to 10.0 G fields. F0 breeding pairs were exposed to MF or sham fields
for 1 week prior to mating, during a 14-week period of cohabitation, and during a
3-week holding period after cohabitation. The duration of the cohabitation period
was selected to be sufficient for the delivery of five litters in the sham
control group. Pups from the final F1 litter from each breeding pair were exposed
to MF or sham fields until sexual maturity, were cohabitated in MF or sham fields
for 7 days with nonsiblings from the same exposure group, and were held in the MF
or sham fields for 22 days to permit delivery of F2 pups for evaluation. No
evidence of exposure-related toxicity was identified in any rat in the F0, F1, or
F2 generations. Fetal viability and body weights in all litters of groups exposed
to MF were comparable to those of sham controls. No significant differences
between sham controls and MF-exposed groups were seen in any measure of
reproductive performance (litters/breeding pair, percent fertile pairs, latency
to parturition, litter size, or sex ratio) in either the F0 or F1 generation.
Exposure of Sprague-Dawley rats to 60-Hz MF strengths of up to 10.0 G either
during their peak reproductive period (F0) or during gestation and throughout
their life span (F1) has no biologically significant effects on reproductive
performance. These results do not support the hypothesis that exposure to pure,
linearly polarized 60-Hz MF is a significant reproductive or developmental
toxicant.
PMID- 10194807
TI - Fetal alcohol syndrome: changes in craniofacial form with age, cognition, and
timing of ethanol exposure in the macaque.
AB - One component of the fetal alcohol syndrome (FAS) facial phenotype is a
frontonasal anomaly characterized by a thin upper lip and a smooth philtrum. The
expression of this anomaly can diminish with age and occurs infrequently in
prenatal alcohol-exposed individuals. This study sought to explain these
observations. Standardized craniofacial cephalograms of 18 nonhuman primates
exposed weekly to ethanol or sucrose solution in utero were measured at ages 1,
6, 12, and 24 months to assess skeletal changes in craniofacial form with age,
cognition, and timing of ethanol exposure. The data suggest that there may be a
critical period for induction of alcohol-induced craniofacial alterations that
occurs very early in gestation and is very short in duration (gestational days 19
or 20). The alterations were scarcely detectable at age 1 month, were most
prominent at 6 months, and diminished progressively at 12 and 24 months in the
macaque. The appearance and disappearance of the thin upper lip and smooth
philtrum may be explained by underlying changes in skeletal structure with age.
The infrequent occurrence of the FAS frontonasal anomaly may be explained, in
part, by its short critical period of induction.
PMID- 10194808
TI - Use of hematoxylin stain to enhance evaluation of heart malformations in the
fetal rat.
AB - Fresh and formalin-fixed visceral microdissection techniques are valuable tools
for studying cardiac teratology in the fetal rat, but are limited by the
difficulty experienced in visualizing the minute structures needing to be
evaluated. This paper describes a simple and quick staining technique used to
enhance the examination procedure. A hematoxylin-saline mixture applied directly
on endothelial-lined surfaces of the heart at different stages during
microdissection greatly improved visualization of membrane-thin structures such
as the pulmonary and aortic semilunar valves, right- and left-side
atrioventricular valves, and atrial and ventricular septa. Hematoxylin staining
of endocardial surfaces is a useful adjunct to the standard visceral
microdissection technique.
PMID- 10194809
TI - Towards new vaccines and modern vaccinology: introductory remarks.
PMID- 10194810
TI - Broadening the approaches to developing more effective vaccines.
AB - Although vaccination has had a dramatic impact on reducing economic losses due to
infectious diseases, vaccination technology has not changed dramatically over the
last 200 years. However, with the advent of biotechnology and our understanding
of virulence factors of infectious agents combined with our knowledge of the host
immune response, we are now witnessing a revolution in the number of new agents
which may potentially be controlled by vaccination, as well as the approaches
being used to develop vaccines. These approaches include subunit vaccines,
genetically modified live vaccines and most recently, polynucleotide vaccines.
Pathogens involved in bovine respiratory disease are used as models to describe
recent advances in developing new vaccines that have the potential to be safer,
more economical and more efficacious. Emphasis will be placed on identification
of specific proteins involved in inducing protective immunity and producing these
in a mammalian expression system as subunit vaccines formulated with adjuvants.
To increase the duration of immunity, the genes encoding these antigens have been
introduced directly into animals as polynucleotide vaccines. The benefits and
short-comings, as well as the practical problems associated (both scientific and
regulatory) with eventual acceptance of these vaccines, are discussed.
PMID- 10194811
TI - New technologies for making vaccines.
AB - Technologies for making active vaccines fall into 3 general groups: live, subunit
(killed or inactivated) and genetic. Each of these groups is further divisible
into multiple categories, which include recombinant-derived antigens as well as
native microorganisms and their components. In addition, there are new enabling
technologies such as delivery systems and vectors which can be applied to these
approaches. Most disease targets, whether infectious or noninfectious in origin,
can be approached by the application of several different vaccine technologies,
as can be tested during the discovery phase of research. The criteria for
choosing early in a development program which of the vaccine technologies are
likely to ultimately be most fruitful for a given application include: knowledge
of the pathogenesis of the given infection/disease; technical feasibility;
immunobiology and associated mechanisms; preclinical efficacy profile;
anticipated clinical safety; regulatory; manufacturing; and marketing. All of
these criteria should be considered together in making selections for an R&D
program. This paper is reviewing the major vaccine technologies and relevant
examples of how these criteria are used to make decisions in vaccine development.
PMID- 10194812
TI - Current paradoxes and changing paradigms in vaccinology.
AB - Other than the provision of clean water, food and sanitation, no other deliberate
human intervention has prolonged the human life span as much as the provision of
vaccines and the control of infectious disease. Since 1950, 25 vaccines have been
licensed in the US, 15 of these for routine universal use in the population. On
the horizon are vaccines not only to prevent infectious diseases, but also
vaccines against cancer and a host of other human ills. Despite these public
health and scientific accomplishments however, the manner in which we think
about, develop and apply vaccines to the public health has common heuristic flaws
which prevent realizing the full benefits of vaccines to society. This paper will
discuss a number of current paradoxes and changing paradigms related to the field
of vaccinology.
PMID- 10194813
TI - DNA immunization: mechanistic studies.
AB - DNA immunization works, as has been amply demonstrated in a variety of microbial
and tumor models. However, the mechanisms which underpin its success remain
unclear. Using intramuscular delivery of DNA, we wish to precisely define how DNA
encoded antigens induce CD8+ T-cells (most cytotoxic T-cells; CTL), CD4+ T-cells
(mostly helper cells) and antibodies; and to use the accrued knowledge to
rationally manipulate DNA vaccines, thus enabling us to optimize each of the
above three types of immune response. We consider it likely that different
mechanisms operate in each case. We have designed a DNA vaccine which induces
CTL, but not antibodies. We will present evidence that CTL are induced by
endogenously-synthesized protein, not by protein released from cells; and that in
the absence of release of intact protein, antibodies are not induced, while CTL
induction remains strong. We have used plasmid-encoded minigenes and have found
that these short sequences also induce CTL; this, too, argues that CTL are
induced by antigens presented following endogenous synthesis. We are attempting
to determine how antigens are released from transfected cells, to interact with B
cells and induce antibodies, and are currently evaluating the CD4 responses
induced by DNA vaccines.
PMID- 10194814
TI - Development and clinical application of new polyvalent combined paediatric
vaccines.
AB - The availability of combined vaccines containing protective antigens against the
majority of (ideally all) diseases for which universal immunization is
recommended in infancy would simplify the implementation, increase the
acceptance, reduce the global cost of immunization programmes and improve disease
control, while offering the possibility of disease elimination or even pathogen
eradication. The desirability of combined vaccines is further enhanced, and made
more urgent, because of the increasing number of diseases that can be prevented
by vaccination. The complicated logistics of administering different vaccines
that each require several inoculations is a significant barrier to successful
immunization of a population. Furthermore, interest in immunization is
continuously gaining momentum since it is now generally recognised that vaccines
are among the safest and most cost-effective medical interventions for infectious
diseases that continue, in spite of the widespread use of efficacious
antimicrobial drugs, to be an important cause of morbidity and mortality. This
burden is likely to increase due to the development of antimicrobial resistance.
Basic research on new vaccines or improvement of existing ones such as the use of
new technologies may be carried out in academic or other non-industrial
laboratories but development work, including the necessary extensive clinical
testing, that lead to products that can be approved for routine use is usually co
ordinated and financed by commercial companies. The decision to develop any
particular combined vaccine will therefore be influenced not only by its medical
desirability and technical feasibility but also the potential financial returns
that the required investments in time and resources may bring to the company. All
major vaccine manufacturers are currently working, either alone or through
strategic alliances, towards developing more polyvalent vaccines by adding
antigens such as inactivated polio virus, conjugated Haemophilus influenzae type
b polysaccharide and hepatitis B surface antigen to the diphtheria-tetanus
pertussis vaccine either in its 'classical' (whole-cell) or more purified
(acellular) formulations. Experience is showing that the development of combined
vaccines involves much more than the simple mixing of existing antigens. Possible
incompatibilities or mutual interferences between the antigens themselves, or
between excipients, preservatives, adjuvants, residual contaminants, stabilisers
and suspending fluids make it mandatory that each formulation be thoroughly
tested for quality, stability, efficacy and safety. Furthermore the ability to
produce and control it consistently must be established before it can be licensed
for commercial use. The progress being made in this field is reviewed.
PMID- 10194815
TI - Promises and pitfalls of meta-analysis in vaccine research.
AB - Meta-analysis continues to grow in usage despite increased concern regarding its
soundness. Over twenty meta-analyses directly pertain to vaccines. Vaccine
researchers need to understand the technique as well as the criticisms. Meta
analysis involves four steps. First, the meta-analyst should establish certain
criteria in advance of the second step where the meta-analyst gathers the data-
the results of the individual studies. Third, the meta-analyst assesses the
individual studies for combinability and, fourth, the meta-analyst actually
combines the data to generate conclusions. Vaccine meta-analyses have addressed a
variety of vaccines and a variety of study objectives including efficacy,
immunogenicity and safety. Three classical concerns revolve around the issue of
publication bias, data dredging and individual study variability. Additionally,
vaccine meta-analyses suffer concerns particular to the field of vaccine
research.
PMID- 10194816
TI - Development of combination vaccines.
AB - Breakthroughs in molecular biology, biochemistry, process development, immunology
and related fields have provided the means for improving current vaccines and
developing new ones. The increasing availability of these vaccines is providing
the unprecedented opportunity to prevent serious infectious disease in different
age groups and to significantly reduce associated morbidity and mortality.
However, since the great majority of licensed and experimental vaccines in
advanced clinical studies are injected, each new vaccine creates the need for
additional needlesticks which could become so numerous as to discourage full
compliance with immunization schedules. Therefore, the development of combination
vaccines is a major way to assure compliance with immunization needs. The leading
types of licensed and experimental vaccines which have been or may be made into
combination vaccines will be described. In addition, key challenges common to the
development of all combination vaccines will be discussed; these include
pharmaceutical, immunological, clinical, regulatory, manufacturing, public health
and marketing issues. In order to assure timely development and availability of
such combination products, these issues must be integrated successfully early in
a development program.
PMID- 10194817
TI - New strategies for combination vaccines based on the extended recombinant
bacterial ghost system.
AB - Controlled expression of cloned PhiX174 gene E in Gram-negative bacteria results
in lysis of the bacteria by formation of an E-specific transmembrane tunnel
structure built through the cell envelope complex. Bacterial ghosts have been
produced from a great variety of bacteria and are used as non-living candidate
vaccines. In the recombinant ghost system, foreign proteins are attached on the
inside of the inner membrane as fusions with specific anchor sequences. Ghosts
have a sealed periplasmic space and the export of proteins into this space vastly
extents the capacity of ghosts or recombinant ghosts to function as carriers of
foreign antigens, immunomodulators or other substances. In addition, S-layer
proteins forming shell-like self assembly structures can be expressed in
bacterial candidate vaccine strains prior to E-mediated lysis. Such recombinant S
layer proteins carrying inserts of foreign epitopes of up to 600 amino acids
within the flexible surface loop areas of the S-layer further extend the
possibilities of ghosts as carriers of foreign epitopes. As ghosts do not need
the addition of adjuvants to induce immunity in experimental animals they can
also be used as carriers or targeting vehicles or as adjuvants in combination
with subunit vaccines. Matrixes like dextran which can be used to fill the
internal lumen of ghosts can be substituted with various ligands to bind the
subunit or other materials of interest. Oral, aerogenic or parenteral
immunization of experimental animals with recombinant ghosts induced specific
humoral and cellular immune responses against bacterial and target components
including protective mucosal immunity. The most relevant advantage of ghosts and
recombinant bacterial ghosts as immunogens is that no inactivation procedures
that denature relevant immunogenic determinants are employed in the production of
ghosts. This fact explains the superior quality of ghosts when compared to other
inactivated vaccines. As carriers of foreign antigens there is no limitation in
the size of foreign antigens to be inserted and the capacity of all spaces
including the membranes, periplasma and internal lumen of the ghosts can be fully
utilized. Using the different building blocks and combining them into the
recombinant ghost system represents a new strategy for adjuvant free combination
vaccines.
PMID- 10194818
TI - New acellular pertussis-containing paediatric combined vaccines.
AB - Combined pediatric vaccines have the advantages of conferring protection against
multiple common infectious diseases with a reduced number of injections. Their
use should lead to better compliance to recommended vaccination schedules.
Diphtheria (D), tetanus (T) and whole-cell pertussis vaccine (P) have been
successfully combined, with or without inactivated poliovirus vaccine (IPV) in
the same syringe for many years. Recently developed acellular pertussis (aP)
Haemophilus influenzae type B (Hib), inactivated poliomyelitis virus and
hepatitis B vaccines are ideal candidates for inclusion in current combined
vaccines. Nevertheless, the development of new combinations has to face
preclinical and clinical issues: the appropriate formulation of the new
antigen(s) and other vaccine components needs to be determined to ensure
compatibility and guard against potential additive or unexpected adverse
reactions; potential immunological interference between antigens and the negative
impact of other vaccine components on immunogenicity may occur, and these have to
be examined also. Whole-cell pertussis vaccines are highly protective against
whooping cough, but the severe adverse reactions that these vaccines sometimes
produce have led to hesitation over their use, including the decision of some
countries to stop pertussis immunization. To increase the acceptability of
pertussis vaccination, Pasteur Merieux Connaught has developed a combined D, T
and a two-component acellular pertussis vaccine (DTaP), composed of purified
pertussis toxoid (PT) and filamentous haemagglutinin (FHA), which has been shown
to be effective in an efficacy trial conducted in Senegal. Acellular DTaP
vaccines are immunogenic and have a better safety profile than DTP vaccines, when
given either for the primary series, for the booster vaccination or for both. In
order to meet worldwide demands, the combined DTaP-IPV or DTP-IPV has been
developed for countries where IPV is recommended. Following the encouragement of
the WHO, an H. influenzae type B tetanus-conjugated (Act-HIB) vaccine, has been
combined in a full liquid formulation with the whole-cell DTP. This vaccine
showed a good safety and immunogenicity profile in infants and in toddlers. A
combined DTaP-IPV-PRP-T vaccine (where the Act-HIB vaccine is reconstituted by
the full-liquid DTaP-IPV) also has been successfully developed both for the
primary series and for booster vaccination; although, a reduced immunogenicity
against PRP observed after the primary series, this did not affect vaccine
priming. Hepatitis B immunization campaigns targeting high-risk groups have
failed to control the disease in areas of low endemicity. In 1992, the WHO
recommended that hepatitis B vaccination should be integrated into the EPI in all
countries by 1997-1999. For that purpose, hepatitis B vaccine is currently
evaluated in pediatric combined vaccines. Developing new combination vaccines is
a difficult but essential process for maintaining high immunization rates
worldwide against infectious diseases, provided that the costs are acceptable.
New combined vaccines including pneumococcal and meningococcal component are
under wide-scale development.
PMID- 10194819
TI - The first combined vaccine against hepatitis A and B: an overview.
AB - Hepatitis A and B infections are prevalent world-wide and are a significant cause
of morbidity and mortality. A vaccine providing dual protection against hepatitis
A and B is now available (Twinrix, SmithKline Beecham Biologicals). Six pivotal
vaccine trials, involving 843 healthy adults, aged between 17 and 60 years and
vaccinated following a 0, 1, 6 month schedule are discussed. At month 2 more than
99% of the vaccinees were seropositive for anti-HAV and 84% were protected
against hepatitis B. The third dose induced a 12-fold increase in geometric mean
titres (GMTs) to 5404 mIU/ml. One month after completion of the vaccination
course nearly all vaccinees had protective titres against hepatitis B with a GMT
of 4818 mIU/ml. Long term follow-up data until month 48 is available for two
studies. At month 48 all 129 vaccinees sampled were still positive for anti-HAV
antibodies and > 95% were still protected against hepatitis B. The combined
hepatitis A and B vaccine Twinrix proves to be consistently safe, well tolerated
and highly immunogenic and compares well with serological responses reached with
monovalent vaccines. This combined hepatitis A and B vaccine offers more
convenience, potentially better compliance and lower administration costs.
PMID- 10194820
TI - A recombinant hybrid outer membrane protein for vaccination against Pseudomonas
aeruginosa.
AB - Among the numerous targets which can be used for the development of vaccines
against Pseudomonas aeruginosa we focused on the outer membrane proteins OprF and
OprI. The C-terminal part of OprF from aa 190 to aa 350 was investigated for its
conservation and its localization of B-cell epitopes. A hybrid protein which
combines the protective epitopes of OprF and OprI was expressed in E. coli and
was proven to be highly protective against an intraperitoneal challenge with P.
aeruginosa by active immunization of immunocompromised mice as well as by passive
immunization of SCID mice with specific antisera. A purification procedure of the
N-terminal His-tagged hybrid antigen was established using immobilized-metal
affinity chromatography. To evaluate its safety and immunogenicity the
recombinant protein was purified for the immunization of human volunteers. The
OprF/OprI hybrid protein is considered to be a candidate for a vaccine against P.
aeruginosa.
PMID- 10194821
TI - The attenuated Salmonella vaccine approach for the control of Helicobacter pylori
related diseases.
AB - The Gram-negative bacterium Helicobacter pylori is a widespread human pathogen
that colonizes the gastric mucosa and is associated with gastro-intestinal
illnesses such as gastritis, peptic ulcer, gastric lymphoma and gastric cancer.
Current pharmacological therapies are becoming less reliable for the control of
H. pylori due to the elevated costs and to the increasing number of antibiotic
resistant strains. New vaccination strategies utilizing H. pylori antigens
combined with adjuvants or delivery of antigens by attenuated Salmonella strains
have been successful in protecting mice against H. pylori infections. Oral
immunization with single doses of urease-expressing Salmonella vaccine strains
elicits mucosal and systemic antibody responses and fully protects different
mouse strains against challenge infections with H. pylori. The high efficacy in
the mouse model, combined with remarkable immunogenicity, safety and low-cost
production, makes attenuated live recombinant Salmonella promising vaccine
candidates for the control of H. pylori-related diseases in humans.
PMID- 10194822
TI - The burden of pneumococcal disease: the role of conjugate vaccines.
AB - The pneumococcus remains a major cause of morbidity and mortality in both
underdeveloped and developed countries. Although there are licensed, safe
vaccines against invasive pneumococcal disease currently available in the US and
Europe, several major dilemmas are apparent. First, the efficacy of these
vaccines in high risk immunocompetent adults is only moderate, with limited or no
immunogenicity in very high risk, immunocompromised adults. Secondly, efficacy of
the vaccine against pneumococcal pneumonia in adults is controversial. Thirdly,
the current vaccines are not efficacious in children < 2 years of age, which is
problematic given the high rate of invasive disease among this age group. The
solution to these dilemmas may lie in the development of protein conjugate
polysaccharide vaccines. This paper briefly reviews the role of conjugate
pneumococcal vaccines.
PMID- 10194823
TI - Herpes simplex virus vaccines.
AB - Herpes simplex virus (HSV) infections are common and produce not only a primary
infection, but also latent and recurrent infections. Therefore, the goals of a
HSV vaccine are different from other vaccines. In this review, the goals of both
prophylactic and therapeutic HSV vaccines are discussed and related to the
immunobiology of acute and recurrent HSV infections. Next, the vaccine strategies
that have been and are being evaluated for control of HSV disease are described.
Current approaches take advantage of many of the modern methodologies for vaccine
development. Thus, as we await final evaluations of subunit HSV glycoprotein
vaccines, early phase I trails are evaluating newer vaccine approaches including
DNA-based vaccines and replication-impaired viruses. The definitive HSV vaccine
may await increased knowledge of the optimal viral antigen(s) and routes to
induce genital tract immunity.
PMID- 10194824
TI - The current status of the rotavirus vaccine.
AB - The US just licensed of an oral tetravalent rhesus reassortant vaccine for
routine immunization of infants against rotavirus. The virus was first identified
25 years ago and is now recognized to be the most common single cause of severe
diarrhea throughout the world. Most children suffer at least one infection and
reinfection is common. Studies of natural immunity show that breastfeeding may
merely delay onset of primary infection and that maternal immunity has little
effect-especially in developing countries where onset in early infancy is common.
Immunity, furthermore, appears to be serotype-specific. Early attempts to develop
a vaccine focused on animal forms of rotavirus. More recent efforts have created
human-animal reassortants that have been far more successful.
PMID- 10194825
TI - Rationale for a vaccine using cellular-derived epitope presented by HIV isolates.
AB - It has been clearly demonstrated that cellular antigens (HLA, beta 2
microglobulin) are incorporated at the virion surface. The same epitope derived
from beta 2-microglobulin is presented on all virus isolates. The peptide was
identified by blocking the neutralizing capacity of a monoclonal antibody
directed to R7V epitope: using this peptide for developing an ELISA, we have
detected antibodies in nonprogressor patients with neutralizing property to
laboratory strains and primary isolates. Purified anti-R7V antibodies
immunoprecipitate all HIV isolates at concentration dependent. R7V is immunogenic
after rabbit immunization and induces HIV immunoprecipitating and neutralizing
antibodies. The patient's as well as the immunized rabbit antibodies did not bind
to any cell. No autoimmune disease is found in nonprogressor patients. For all
these reasons, R7V is a good candidate for an universal AIDS vaccine.
PMID- 10194826
TI - Correlates of protection, antigen delivery and molecular epidemiology: basics for
designing an HIV vaccine.
AB - Major obstacles in the development of HIV vaccines are the high variability of
the virus and its complex interaction with the immune system. Recent studies
demonstrated, that CTLs recognizing highly conserved epitopes in the group
specific antigen are capable of controlling HIV-replication in long-term
nonprogressors. Necessary consequences for novel vaccine concepts are the
presentation of a large repertoire of antigenic sites as well as the stimulation
of different effectors of the immune system. Accordingly, different types of
recombinant HIV-1 virus-like particles (VLPs) have been constructed stimulating
the induction of neutralizing antibodies and HIV-specific CD8-positive CTL
responses in preclinical studies. With respect to future vaccine trials, HIV
vaccine formulations may need to be tailored to the local strains circulating
within a geographical region. The expert group of the joint United Nations
Programme on AIDS recently identified Yunnan, a southwestern province of China,
as a region, in which the HIV epidemic is starting to gain speed, resembling to
the situation in Thailand 10 years ago. A molecular clone of a representative
virus strain is now available for the development of innovative antigen delivery
systems aiming to be evaluated in future clinical vaccine trials throughout this
area.
PMID- 10194827
TI - Immunization with a plasmid encoding a modified hepatitis B surface antigen
carrying the receptor binding site for hepatocytes.
AB - Intramuscular injection of a plasmid encoding a modified hepatitis B surface
antigen (HBsAg) induced humoral and cytotoxic responses in C57BL/6 mice. This
modified HBsAg contains a preS1-derived peptide (amino acids 21 to 47), that
carries the HBV receptor binding site for hepatocytes fused to the C-terminus of
the small protein (at the position of amino acid 223). After a single DNA
injection, the immunized mice elicited high titers of anti-HBs and anti-preS1
antibodies, and produced strong HBV specific cytotoxic T-lymphocyte (CTL)
responses. The immune response induced after a single injection of this modified
HBsAg gene in HBsAg-transgenic mice resulted in the clearance of circulating
HBsAg and the appearance of anti-HBs and anti-preS1 antibodies. The high titers
of preS1 antibody in transgenic mice were comparable to those found in non
transgenic controls and may be efficient to clear Dane particles existing in sera
from chronic carriers. These data indicated that a genetic vaccine consisting of
this modified HBsAg gene may have a potential use for both prophylactic and
therapeutic purposes.
PMID- 10194828
TI - Immunogenetic mechanisms of antibody response to measles vaccine: the role of the
HLA genes.
AB - Measles is the most transmissible human disease known to date. In the prevaccine
era, virtually every member of each birth cohort was infected with this virus,
leading to substantial morbidity and mortality, with millions of deaths on a
global scale. At the current time, measles causes an estimated 1 to 1.5 million
deaths per year world-wide. Since the advent of live, attenuated measles vaccines
measles has been controlled, but not eradicated. Central to the goal of measles
eradication are data relating to the influence of immunogenetics on vaccine
immunogenicity. In this paper, the results of studies are reviewed executed in my
laboratory examining the role of the class I and II HLA genes on the antibody
response to measles vaccine.
PMID- 10194829
TI - Measles vaccines, new developments and immunization strategies.
AB - The development of an attenuated measles virus vaccine gave us a tool to combat a
disease which has ravaged the child population throughout the centuries. Three
decades later the vaccine has shown its qualities and its problems. Using this
vaccine the WHO have decided on a measles eradication policy. This article
discusses some of the issues which are being addressed and possible solutions.
PMID- 10194830
TI - Strategies to prevent and control hepatitis B and C virus infections: a global
perspective.
AB - Hepatitis B virus (HBV) and hepatitis C virus (HCV) are major causes of acute and
chronic liver disease worldwide. Chronic infection with these viruses often leads
to chronic liver disease, including cirrhosis or primary hepatocellular
carcinoma. Both HBV and HCV are bloodborne viruses; however, HBV is transmitted
efficiently by both percutaneous and mucosal exposures, and HCV is transmitted
predominantly by percutaneous exposures. Because the relative importance of
various modes of transmission of these viruses differs by country, the choice of
specific prevention and control strategies depends primarily on the epidemiology
of infection in a particular country. Comprehensive hepatitis B prevention
strategies should include (1) prevention of perinatal HBV transmission, (2)
hepatitis B vaccination at critical ages to interrupt transmission and (3)
prevention of nosocomial HBV transmission. The prevention of hepatitis C is
problematic because a vaccine to prevent HCV infection is not expected to be
developed in the foreseeable future. From a global perspective, the greatest
impact on the disease burden associated with HCV infection will most likely be
achieved by focusing efforts on primary prevention strategies to reduce or
eliminate the risk for transmission from nosocomial exposures (e.g. blood
transfusion, unsafe injection practices) and high-risk practices (e.g. injecting
drug use).
PMID- 10194831
TI - Immunization programme against hepatitis B virus infection in Italy: cost
effectiveness.
AB - In Italy in the 1980s the extent of viral hepatitis B infection was on average
about 11,000 symptomatic cases of acute viral hepatitis (AVH) per year
(19/100,000 inhabitants). The prevalence of HBsAg carriers in the general
population was about 3% and in pregnant women 2.4%. 64,000 people were affected
by chronic viral hepatitis (CVH) or cirrhosis (prevalence rate 112/100,000) and
3400 by hepatocellular carcinoma (HCC) (prevalence rate 5.9/100,000). To reduce
these HBV related pathologies in the Italian population, universal vaccination of
newborn babies, 12-year old adolescents and high risk groups was implemented in
1991. The annual cost of this immunization is about 57 million 544 thousand USD:
direct costs: 41 million 34 thousand USD; indirect costs: 16 million 510 thousand
USD. Concerning the vaccination impact on HBV endemicity in Italy, we found a
significant reduction of acute viral hepatitis incidence (4.2/100,000 in 1996
versus 19/100,000 in the '80s) and HBsAg carrier prevalence (0.9% in 1997 versus
3% in the '80s). As for the assistance and social cost of acute viral hepatitis
occurring from 1991 to 1996 (17,608 cases) it was 238 million 908 thousand USD,
while the cost for the same pathology in the years from 1985 to 1990 (35,614
cases) was 483 million 216 thousand USD. Thus, the saving during the years of the
vaccination was evaluated in 244 million 308 thousand USD. At the moment, we have
no information about the reduction in chronic sequelae of HBV pathology as an
effect of the vaccination, because the incidence of this pathology generally
starts to appear after 15 years (in our case in 2006).
PMID- 10194832
TI - Rabipur: a reliable vaccine for rabies protection.
AB - Rabipur, a vaccine propagated on chick embryo fibroblasts, is one of the 'second
generation' rabies vaccines produced by cell culture techniques. It compares in
tolerance, immunogenicity and efficacy with the human diploid cell culture
vaccines and is significantly more economical to be produced. It has proven to be
an excellent vaccine, particularly when employed by the 2-1-1 schedule
vaccination. This approach combines economy of vaccine with increased safety of
treatment. Rabipur was investigated in all immunological parameters and can be
recommended as a vaccine of choice for postexposure rabies treatment.
PMID- 10194833
TI - Rabies--risk of exposure and current trends in prevention of human cases.
AB - According to official WHO data more than 2.5 billion people are at risk in over
100 countries reporting the disease. Rabies mortality ranks ten in all infectious
diseases worldwide. There are still about 50,000 to 60,000 human deaths annually
although effective vaccines for post-exposure treatment are available. Most
affected are the tropical countries in Africa, Asia, South America, and Oceania.
The mortality figures range from about 0.001 per 100,000 for the US to 18 per
100,000 in Ethiopia. The vast majority (95-98%) of the 60,000 annual human death
cases worldwide occur in canine (dog rabies) endemic regions with large stray dog
population. Control of the disease is hampered by cultural, social and economic
realities. In the rabies infested developing countries modern cell culture
vaccines are hardly affordable. Dangerous neural tissue derived vaccines are
still used. Three dose-saving treatment schedules have been developed: The
reduced dose intramuscular 2-1-1 regimen, the two-site intradermal and the 8-site
intradermal regimen. There is a critical shortage of human and purified equine
rabies immunoglobulins, which are essential biologicals in the treatment of
severe exposures.
PMID- 10194834
TI - Epidemiology and control of fox rabies in Europe.
AB - During recent years, most of the research on the control of sylvatic rabies has
concentrated on developing methods of oral vaccination of wild rabies vectors. In
order to improve both the safety and the stability of the vaccine used, a
recombinant vaccinia virus which expresses the immunizing glycoprotein of rabies
virus (VRG) has been developed and extensively tested in the laboratory as well
as in the field. From 1989 until 1995, several million VRG vaccine doses have
been dispersed in western Europe for vaccination of red foxes. In Europe, the use
of VRG has lead to the elimination of sylvatic rabies from large areas, which
have consequently been freed from vaccination. This may have consequences on the
regulation of pets movements within the whole European Union.
PMID- 10194835
TI - Prevention measures against foot-and-mouth disease in Europe in recent years.
AB - The paper describes the situation of foot-and-mouth disease in Europe over the
past 2 years and analyses the origin of the disease during the last decades.
Preventive vaccination has been banned in Europe in the early nineties. Since
then, despite several incursion of the virus, the disease has always been rapidly
contained and eradicated. Therefore the ban on vaccination did not result in an
increase of FMD outbreaks. Based on the recent source of introduction of the
virus, the author reviews the lines of defence which should be reinforced to
reduce the risk of further introduction of the disease.
PMID- 10194836
TI - Vital elements for the successful control of foot-and-mouth disease by
vaccination.
AB - The efficient control of foot-and-mouth disease (FMD) by immunisation depends not
only on the appropriate choice of vaccine in terms of innocuity, potency and
strain composition, but also on a series of inter-related zoo-sanitary factors
which are equally important. These include: national, centralised planning
(including contingency planning) and control; vaccination and revaccination
policy; the availability of epizootiological intelligence based on adequate
diagnostic capability and ongoing immunological surveillance; the logistics of
supply with its components of storage, transport and distribution; proper vaccine
application; cleaning and disinfection of premises, vehicles and personnel;
identification of individual animals; control of animal movement; recording;
ongoing economic outcome and benefit analyses: training and retraining of
professional and technical staff; public relations and especially the commitment
of the agricultural community. These elements are reviewed in this paper.
PMID- 10194837
TI - Optimisation of the immune response to foot-and-mouth disease vaccines.
AB - Considering the many variables influencing the immune response of the host to
vaccination against foot-and-mouth disease (FMD), the properties and
characteristics of the vaccine and recommendations concerning its mode of
application offer the best opportunity for the manufacturer to provide safe,
effective protection of livestock. There are a number of critical elements in the
production of FMD vaccines, such as the selection of appropriate strain(s), which
have a direct bearing on the quality of the immune response. Equally, development
of effective immunity depends on proper and timely application of good quality
vaccine. In contrast, several of the potential variables in vaccination against
FMD such as the use of oil adjuvants for cattle are probably less critical than
is sometimes perceived. This presentation considers some of the many variables
involved in the production and use of FMD vaccines.
PMID- 10194838
TI - Foot-and-mouth disease: current world situation.
AB - Foot-and-mouth disease (FMD) has increased in significance as a major constraint
to international trade in live animals and animal products as the World Trade
Organization agreements remove other obstructions. A consequence will be
reluctance to immediately declare the presence of FMD if it is thought possible
to quickly eliminate its presence and so avoid trade embargoes. This will
predispose to spread of disease between trading partners. In addition, as
countries tend to increase the requirements for testing and certification of
imported animals with the objective of reducing the risk of importing disease,
the increased costs and delays that this involves will encourage the illegal
trade and therefore have the converse result.
PMID- 10194839
TI - Killed whole bacterial cells, a mucosal delivery system for the induction of
immunity in the respiratory tract and middle ear: an overview.
AB - Infectious diseases remain a leading cause of morbidity and mortality worldwide
with mucosal membranes being the most frequent portals of entry of pathogenic
micro-organisms. This has prompted studies aimed at the development of
vaccination protocols that would lead to an increased protection of mucosae
through an understanding of the common mucosal immune system as an immune
communication network between mucosal sites. Recent studies have suggested that
preferential sub-networks exist within the system and these studies have
exploited the gut-associated lymphoid tissue (GALT)-lung sub-network in the
development of oral vaccine strategies for infections of the respiratory tract
and middle ear. Mucosal immunization with whole formalin killed Pseudomonas
aeruginosa (Pa), Branhamella catarrhalis, nontypable Haemophilus influenzae
(NTHi) or Streptococcus pneumoniae (Spn) results in enhanced homologous bacterial
clearance from the lung of immune animals challenged with live bacteria. These
studies have been extended to the middle ear where similar results have been
observed for NTHi and Spn. Mechanisms responsible for inducing enhanced bacterial
clearance from the airways include opsonising antibody, antigen specific CD4+ T
helper cells, cytokine responses and recruitment of activated polymophonuclear
neutrophils. The mechanisms induced by immunization which stimulates the immune
system to rapidly mobilise both innate and specific immune responses during
infection are the subject of ongoing research.
PMID- 10194840
TI - Adjuvant activity of immunopotentiating reconstituted influenza virosomes
(IRIVs).
AB - Using immunopotentiating, reconstituted influenza virosomes (IRIV) as a delivery
vehicle, a number of vaccines have been developed. In humans, IRIV-based vaccines
containing hepatitis A and influenza antigens have been found to possess enhanced
immunogenicity compared to alum-adsorbed vaccine for hepatitis A or commercial
subunits or whole virion influenza vaccines. These vaccines were safe and did not
engender any antiphospholipid antibodies against the liposome components of the
IRIV. Hepatitis B, tetanus toxoid and diphtheria toxoid, and nucleic acids have
also been incorporated into IRIVs. These vaccines are now undergoing clinical
phase I testing. IRIVs are also being evaluated in phase I trials for their
ability to deliver antigens by the intranasal route.
PMID- 10194841
TI - Liposome-mediated immunotherapy against respiratory influenza virus infection
using double-stranded RNA poly ICLC.
AB - The use of liposome delivery technology to enhance the antiviral activity of poly
ICLC (an immunomodulating dsRNA) while decreasing its intrinsic toxicity is
evaluated in this study. The antiviral efficacies of free and liposome
encapsulated poly ICLC were evaluated and compared using a lethal respiratory
influenza A virus infection in mice. The toxicity profiles of free and liposome
encapsulated poly ICLC were compared by determining the extent of hypothermia and
loss in body weights in mice pretreated with these drugs. Poly ICLC was
encapsulated in cationic liposomes prepared by the freeze drying method. To
determine the antiviral efficacies of free and liposome-encapsulated poly ICLC,
mice were intranasally pretreated with two doses of poly ICLC (free or liposomal,
1 mg/kg/dose) given 48 h apart. At various times post pretreatment, mice were
intranasally challenged with 10 LD50 mouse-adapted influenza A/PR/8 (H1N1) virus.
The survival rates of the mice were determined at day 14 post infected and
compared to the untreated control mice. Results indicate mice pretreated with
liposome-encapsulated poly ICLC within 3 weeks prior to virus challenge were
completely protected (100% survival compared to 0% for the untreated control
group, p < 0.001), while window of protection provided by free unencapsulated
poly ICLC was 12 days. When the toxicity profiles of free and liposome
encapsulated poly ICLC were compared, it was found that hypothermia and body
weight loss induced by poly ICLC were either completely mitigated or
significantly reduced in mice given equivalent doses of poly ICLC in the liposome
encapsulated form. These results suggest that liposomes are an excellent drug
carrier for poly ICLC, that liposome-encapsulated poly ICLC may provide a safe
and effective immunotherapeutic approach for the prevention of respiratory
influenza virus infections.
PMID- 10194842
TI - Dry powder inhalation as a potential delivery method for vaccines.
AB - Measles vaccine is administered to millions of children annually via a
percutaneous injection. There are, however, compelling reasons to search for
alternative routes of administration, especially in mass vaccination campaigns.
Two key factors are (1) decreased stability of the vaccine upon reconstitution
and, (2) the potential risks of contamination associated with needles. Dura has
developed a unique inhaler that can deliver a powder dose via the pulmonary route
for local or systemic action. The breath-actuated Spiros inhaler uses
electromechanical energy to aerosolize and deliver a consistent dose over a wide
range of inspiratory flow rates. To achieve alveolar (deep lung) deposition for
subsequent systemic absorption, dry-powder vaccine is size reduced to a mass
median diameter between 1 and 5 microns. Small vaccine particles are blended with
an inert carrier to improve dispersion. Measles vaccine formulated as a powder
blend may be more thermostable than existing reconstituted formulations. The
Spiros technology is available in three powder storage platforms. Two of these
formats are designed specifically for moisture and/or light sensitive compounds
and may be particularly suitable for delivery of measles vaccines in mass
campaigns because their design (1) eliminates the need for powder reconstitution,
and (2) reduces the risk of contamination.
PMID- 10194843
TI - Oral vaccination of animals with antigens encapsulated in alginate microspheres.
AB - Most infectious diseases begin at a mucosal surface. Prevention of infection must
therefore consider ways to enhance local immunity to prevent the attachment and
invasion of microbes. Despite this understanding, most vaccines depend on
parenterally administered vaccines that induce a circulating immune response that
often does not cross to mucosal sites. Administration of vaccines to mucosal
sites induces local immunity. To be effective requires that antigen be
administered often. This is not always practical depending on the site where
protection is needed, nor comfortable to the patient. Not all mucosal sites have
inductive lymphoid tissue present as well. Oral administration is easy to do, is
well accepted by humans and animals and targets the largest inductive lymphoid
tissue in the body in the intestine. Oral administration of antigen requires
protection of antigen from the enzymes and pH of the stomach. Polymeric delivery
systems are under investigation to deliver vaccines to the intestine while
protecting them from adverse conditions that could adversely affect the antigens.
They also can enhance delivery of antigen specifically to the inductive lymphoid
tissue. Sodium alginate is a readily available, inexpensive polymer that can be
used to encapsulate a wide variety of antigens under mild conditions. Orally
administered alginate microspheres containing antigen have successfully induced
immunity in mice to enteric (rotavirus) pathogens and in the respiratory tract in
cattle with a model antigen (ovalbumin). This delivery system offers a safe,
effective means of orally vaccinating large numbers of animals (and perhaps
humans) to a variety of infectious agents.
PMID- 10194844
TI - [The lung as an immunologic organ].
AB - Immune response and restructuring of tissue during organ fibrosis mutually
influence each other. It has become evident that the immunomodulatory properties
of lining cells of the lung, such as bronchial or alveolar epithelial cells or
pulmonary endothelial cells exert a major influence on the acute and chronic
activation of the immune system. On the other hand, recent data obtained under in
vivo conditions, suggest that the process of mesenchymal organ remodelling during
inflammation not only causes organ fibrosis, but may actually perpetuate the
process of chronic pulmonary inflammation due to its immunosuppressive effects.
In this short review, two examples for this reciprocal influence are discussed.
PMID- 10194845
TI - [Pathophysiology and respiratory therapy of chronic respiratory insufficiency in
chronic pulmonary fibrosis].
PMID- 10194846
TI - [Operative management of trigono-atrial lesions].
AB - Trigono-atrial-Lesions are microsurgically serios accessible, the results of
transcortical aproaches are difficult and frequently unsatisfactory. The
microsurgical anatomy of the trigono-atrial region will be studied on 100 brain
hemispheres (the posterior cerebral arteries were injected selective on 70
hemispheres). According to the anatomical findings, an interhemispheric
microsurgical approach has been developed. The operative results of 25 patients
with different atrial lesions are presented. There was no operative mortality,
the postoperative morbidity was 12%, in 24% (n = 6) the preoperative state was
still unchanged, in 12 cases (48%) we note a normal neurological and
neuropsychological postoperative status. In 4 patients (16%) the neurological
symptoms are postoperatively improved. According to these first results, the
described transatrial approach seems to be a real alternative for careful
selected meanly leftsided lesions of the trigone.
PMID- 10194847
TI - [Visual evoked potentials as an indicator of supratentorial and infratentorial
herniation].
AB - The VEP was investigated in 172 patients with infratentorial and in 100 patients
with supratentorial space occupying lesions. In each group 65% of the patients
showed marked or even extensive changes in VEP. An immediate relation of the
lesion to the optochiasmatic system or a hydrocephalus was noted in a few cases
only. In contrast the VEP of patients with a clear transtentorial herniation
showed severely pathological changes, occasionally up to complete loss of the
potential. The VEP changes were reversible on removal of the space occupying
lesions in all patients. The constellation of VEP changes in subgroups of
patients with different types of the space occupying lesions, as well as the
observed symmetry of the VEP changes, allow the assumption that the functional
inhibition of the optic pathway occurs in the perimesencephalic part via their
compression or stretching. The assumption is supported by pathoanatomical MRT
findings in some cases. It seems, therefore, that VEP investigations enable the
registration of a compression or torsion of the cranial mesencephalon
(mesencephalo-diencephalic mechanical irritation) or the presence of a clinical
silent transtentorial herniation in space occupying lesions. The loss of the VEP
appears to yield an early and certain signal of the progressing mid-brain
syndrome.
PMID- 10194848
TI - [[Assessment of quality of life of patients with brain tumors].
AB - In the treatment of patients with brain tumours, quality of life, as subjectively
assessed according to the needs, stresses and circumstances of the patient and
the subjectively experienced effects of the brain tumour, has recently been
considered. While much has been written relating to the difficulty in defining
and measuring the construct "quality of life" in the fields of clinical oncology
and geriatrics, possible alterations in the quality of life following brain
tumour have been largely ignored. The present article describes the targets of
research on quality of life in brain tumour patients and difficulties in defining
this construct. Furthermore, it discusses the limitations of the assessment of
quality of life, in particular with regard to available tests and the reliability
of brain damaged patients' self-assessment. In addition, a short overview is
given concerning research on quality of life in meningioma patients.
PMID- 10194849
TI - Bedside-microdialysis for early detection of vasospasm after subarachnoid
hemorrhage. Case report and review of the literature.
AB - Continuous monitoring of cerebral metabolism would be desirable for early
detection of vasospasm in SAH patients. Bedside-microdialysis, a new technique
for on-line monitoring of cerebral metabolism, may reflect changes seen in
cerebral vasospasm diagnosed by transcranial Doppler sonography (TCD). This
report represents the first case of combined TCD monitoring and on-line
microdialysis from the brain extracellular fluid in a SAH patient. A 48-year-old
woman suffered subarachnoid hemorrhage grade IV according to Hunt and Hess.
Angiography revealed an aneurysm of the left carotid artery. The aneurysm was
clipped 45 hours after bleeding. The microdialysis catheter was inserted after
aneurysm clipping into the white matter of the left temporal lobe. Sampling of
microdialysates started immediately, analyzing time for glucose, lactate,
pyruvate and glutamate was four minutes. Postoperatively, the patient was doing
well and microdialysis and TCD parameters remained within normal range. On the
third postoperative day a shift to anaerob metabolism (decrease of glucose,
increase of lactate and the lactate-pyruvate ratio up to pathological levels) and
an increase in glutamate was observed suggesting insufficient cerebral perfusion.
The patient progressively deteriorated clinically. Vasospasm was diagnosed by TCD
monitoring 36 hours after onset of ischemic changes monitored by microdialysis.
After elevation of mean arterial blood pressure, TCD values and metabolic
parameters normalized. Interestingly, the pathological changes in on-line
microdialysis preceded the typical increase in blood flow velocity by TCD and the
clinical deterioration. Our case suggests, that bedside-microdialysis may be
useful for early detection of vasospasm and continuous surveillance of treatment
and may be a new guide to treat ischemic neurological deficits following SAH.
PMID- 10194850
TI - Giant cavernous hemangioma of the scalp.
AB - In this article, a quite rare giant cavernous hemangioma located in right
frontoparietal region of a 16 year-old boy is presented. Cavernous hemangiomas
are commonly seen in extremities, neck, face and sometimes scalp, cutaneous or
subcutaneous in localization. Giant cavernous hemangioma in the right
frontoparietal region have been seen in two cases so far. In this article, we
discussed the differential diagnosis, characteristics and therapy methods of
giant cavernous hemangioma of the scalp.
PMID- 10194851
TI - Production of ginseng and its bioactive components in plant cell culture: current
technological and applied aspects.
AB - Ginseng (the root of Panax ginseng CA Mayer) is a valuable oriental herb, which
has been used in traditional Chinese medicine for thousands of years, both as a
disease-healing drug and a general tonic. The medicinal value of ginseng is now
also widely recognized in the west and the world ginseng market is expanding. The
current supply of ginseng depends mainly on field cultivation, which is a slow
and laborious process. Plant cell and tissue culture methods have been explored
as potentially more efficient alternatives for the mass production of ginseng and
its bioactive components. Research into ginseng cell and tissue cultures started
in the early 1960s and commercial applications have been underway since the late
1980s. The ginseng cell culture has continued to attract considerable research
and development effort in recent years as scientists seek to understand and
optimize the culture conditions. In this paper, we review recent studies on
ginseng cell culture processes, focusing on the physiological and bioengineering
factors affecting the productivity of ginseng biomass and useful metabolites
(e.g. ginseng saponin and polysaccharide) and the progress and concerns in large
scale applications.
PMID- 10194852
TI - Cloning, nucleotide sequence and expression of a new L-N-carbamoylase gene from
Arthrobacter aurescens DSM 3747 in E. coli.
AB - An L-N-carbamoyl amino acid amidohydrolase (L-N-carbamoylase) from Arthrobacter
aurescens DSM 3747 was cloned in E. coli and the nucleotide sequence was
determined. After expression of the gene in E. coli the enzyme was purified to
homogeneity and characterized. The enzyme was shown to be strictly L-specific and
exhibited the highest activity in the hydrolysis of beta-aryl substituted N alpha
carbamoyl-alanines as e.g. N-carbamoyl-tryptophan. Carbamoyl derivatives of beta
alanine and charged aliphatic amino acids were not accepted as substrates. The N
carbamoylase of A. aurescens DSM 3747 differs from all known enzymes with respect
to its substrate specificity although amino acid sequence identity scores of 35
38% to other N-carbamoylases have been detected. The enzyme consists of two
subunits of 44,000 Da, and has an isoelectric point of 4.3. The optima of
temperature and pH were determined to be 50 degrees C and pH 8.5 respectively. At
37 degrees C the enzyme was completely stable for several days.
PMID- 10194853
TI - Enhancing recombinant protein yields in Escherichia coli using the T7 system
under the control of heat inducible lambda PL promoter.
AB - A recombinant plasmid containing the complete lacZ gene downstream of the T7
promoter was used to transform Escherichia coli containing another plasmid which
had the T7 RNA polymerase gene under the control of heat inducible lambda PL
promoter. This recombinant E. coli containing the two plasmids was studied in
order to enhance beta-galactosidase expression. The heat shock time which
effectively regulates the T7 RNA polymerase was optimized and best expression of
beta-galactosidase was obtained with 2 min heat shock. Substrate feeding
increased the duration of log phase and allowed induction at a higher cell
density without affecting the specific activity. A high cell density (7 g l-1)
and high specific activity (approximately 20,000 U) were achieved which
effectively increased the product concentration 18-fold.
PMID- 10194854
TI - Inclusion body purification and protein refolding using microfiltration and size
exclusion chromatography.
AB - The presence of inclusion body impurities can affect the refolding yield of
recombinant proteins, thus there is a need to purify inclusion bodies prior to
refolding. We have compared centrifugation and membrane filtration for the
washing and recovery of inclusion bodies of recombinant hen egg white lysozyme
(rHEWL). It was found that the most significant purification occurred during the
removal of cell debris. Moderate improvements in purity were subsequently
obtained by washing using EDTA, moderate urea solutions and Triton X-100.
Centrifugation between each wash step gave a purer product with a higher rHEWL
yield. With microfiltration, use of a 0.45 micron membrane gave higher solvent
fluxes, purer inclusion bodies and greater protein yield as compared with a 0.1
micron membrane. Significant flux decline was observed for both membranes.
Second, we studied the refolding of rHEWL. Refolding from an initial
concentration of 1.5 mg ml-1, by 100-fold batch dilution gave a 43% recovery of
specific activity. Purified inclusion bodies gave rise to higher refolding
yields, and negligible activity was observed after refolding partially purified
material. Refolding rHEWL with a size exclusion chromatography based process gave
rise to a refolding yield of 35% that corresponded to a 20-fold dilution.
PMID- 10194855
TI - Safety of industrial lactic acid bacteria.
AB - Lactic acid bacteria (LAB) are ubiquitous in fermented and non-fermented foods
and are common components of the human commensal microflora. This long history of
human exposure and consumption has led to the reasonable conclusion that they are
generally safe. Recent attention has also focused on their possible role as
probiotic bacteria, promoting beneficial health effects. There have, however,
been a number of reports of human infections caused by LAB and these are
reviewed. In most cases, the source of the infection was the commensal LAB flora
rather than ingested bacteria and the patient had some underlying disease or
predisposing condition. Even as opportunistic pathogens, the LAB, with the
notable exception of the enterococci, are much less successful than a number of
other members of the commensal microflora. The use of new strains for probiotic
use is likely to require more detailed evidence for their safety, particularly if
the strains have been genetically modified or have been derived from animals.
Procedures that have been proposed for assessing the safety of new strains are
described.
PMID- 10194856
TI - Factors influencing the potential use of Aliquat 336 for the in situ extraction
of carboxylic acids from cultures of Pseudomonas putida.
AB - The use of extraction techniques to alleviate product inhibition in bioprocesses
is one of a number of potential separation methods. However, the intimate contact
of an organic phase with the broth implies that the organic components of this
phase may be present in the aqueous phase at saturation levels. The quaternary
amine Aliquat 336 (trioctyl/decylmethylammonium entity), dissolved in octan-1-ol
showed no inhibition on the growth of Pseudomonas putida, at least with respect
to molecular toxicity. Nevertheless, it is important to point out two main
effects of Aliquat 336 associated with its ion exchange properties. It is able
(1) to complex hydroxyl ions and therefore drastically lower the pH of the broth
and (2) release its counter ion through these exchanges. Therefore, a strict
control of the pH of the cultivation must be conducted, with the constraint that
Ps. putida has an optimal pH growth of 7.4-7.5. The pH range tolerated by this
strain is, however, between 5.0 and 9.0. In addition, the counter ion of Aliquat
336 needs to be carefully chosen and HSO4- should be preferred to Cl-.
PMID- 10194857
TI - Investigation of the impact of MIG1 and MIG2 on the physiology of Saccharomyces
cerevisiae.
AB - The gene functions of MIG1 and MIG2 are well known for their role in glucose
control in Saccharomyces cerevisiae. A prototrophic mig1 disruptant (T468) and
mig1mig2 double disruptant (T475) as well as their congenic wild-type strain
(CEN.PK 113-7D) were analysed for changes in their peripheral metabolism (batch
cultivations on sugar mixtures) and central metabolism (batch and continuous
cultivations as well as acceleratostats). Sucrose metabolism was alleviated of
glucose control in the mig1 disruptant, and even more so in the mig1mig2
disruptant compared with their wild-type strain. The lag phase in a batch
cultivation grown on a glucose-galactose mixture was reduced by 50% in either
disruptant, i.e. additional disruption of MIG2 in a mig1 background did not
further alleviate galactose metabolism from glucose control. In contrast, both
disruptants exhibited a more stringent glucose control of maltose metabolism
compared with the wild-type strain. Growing on glucose, the mig1mig2 double
disruptant exhibited a 12% higher specific growth rate than the wild-type strain,
as well as a significantly higher respiratory capacity.
PMID- 10194858
TI - Hybridoma cell growth and anti-neuroblastoma monoclonal antibody production in
spinner flasks using a protein-free medium with microcarriers.
AB - The main disadvantages of foetal calf serum as the world-wide common serum
supplement for cell growth are its content of various proteins of variable
concentrations between batches as well as its high cost. The use of serum-free
and protein-free media is gradually becoming one of the goals of cell culture
especially for standardizing culture conditions or for simple purification of
cell products like monoclonal antibodies. The mouse hybridoma cells 14/2/1 were
cultivated either in protein-free UltraDOMA medium or in serum-containing RPMI
medium with and without microcarriers to generate high quantities of monoclonal
antibodies against neuroblastoma tumour cells. Cell growth rate, IgG production,
viability, glucose and lactate concentrations, attachment rate and doubling time
have been used as investigation criteria. Modifications of culture procedures
(static or stirred), inoculum density, and microcarrier concentration caused an
improvement of monoclonal antibody production. The kinetics of antibody synthesis
was best in spinner culture with 2 ml of microcarriers in protein-free medium.
These results of short-term microcarrier culture in stirred spinner flasks
indicate that IgG yields in protein-free medium 2.5-fold higher to those in serum
supplemented medium can be achieved.
PMID- 10194859
TI - Purification, characterization, and application of an acid urease from
Arthrobacter mobilis.
AB - It has been shown that urea in fermented beverages and foods can serve as a
precursor of ethylcarbamate, a potential carcinogen, and acid urease is an
effective agent for removing urea in such products. We describe herein the
purification and characterization of a novel acid urease from Arthrobacter
mobilis SAM 0752 and show its unique application for the removal of urea from
fermented beverages using the Japanese rice wine, sake, as an example. The
purified acid urease showed an optimum pH for activity at pH 4.2. The enzyme
exhibited an apparent K(m) for urea of 3.0 mM and a Vmax of 2370 mumol of urea
per mg and min at 37 degrees C and pH 4.2. Gel permeation chromatographic and
sodium dodecyl sulfate gel electrophoretic analyses showed that the enzyme has an
apparent native molecular weight (M(r)) of 290,000 and consisted of three types
of subunit proteins (M(r), 67,000, 16,600, 14,100) denoted by alpha, beta, and
gamma. The most probable stoichiometry of the subunits was estimated to be alpha:
beta: gamma = 1:1:1, suggesting the enzyme subunit structure of (alpha beta
gamma)3. The enzyme also existed as an aggregated form with an M(r) of 580,000.
The purified enzyme contained 2 g-atom of nickel per alpha beta gamma unit of the
enzyme. Enzyme activity was inhibited by acetohydroxamic acid, HgCl2, and CuCl2.
The isoelectric point of the native enzyme was estimated by gel electrofocusing
to be 6.8. Urea (50 ppm), which was exogenously added to sake (pH 4.4, 17 +/- 1%
(v/v) ethanol), was completely decomposed by incubation with the enzyme (0.09 U
ml-1) at 15 degrees C for 13 days. The enzyme was unstable at temperatures higher
than 65 degrees C and pHs lower than 4, and was completely inactivated under the
conditions of a pasteurization step involved in the traditional sake-making
processes. These results indicate that the enzyme is applicable to the
elimination of urea in fermented beverages with minimal modification to the
conventional process.
PMID- 10194860
TI - Facilitated geranylgeranylation of shrimp ras-encoded p25 fusion protein by the
binding with guanosine diphosphate.
AB - A cDNA was isolated from the shrimp Penaeus japonicus by homology cloning.
Similar to the mammalian Ras proteins, this shrimp hepatopancreas cDNA encodes a
187-residue polypeptide whose predicted amino acid sequence shares 85% homology
with mammalian KB-Ras proteins and demonstrates identity in the guanine
nucleotide binding domains. Expression of the cDNA of shrimp in Escherichia coli
yielded a 25-kDa polypeptide with positive reactivity toward the monoclonal
antibodies against Ras of mammals. As judged by nitrocellulose filtration assay,
the specific GTP binding activity of ras-encoded p25 fusion protein was
approximately 30,000 units/mg of protein, whereas that of GDP was 5,000 units/mg
of protein. In other words, the GTP bound form of ras-encoded p25 fusion protein
prevails. Fluorography analysis demonstrated that the prenylation of both shrimp
Ras-GDP and shrimp Ras-GTP by protein geranylgeranyltransferase I of shrimp
Penaeus japonicus exceeded that of nucleotide-free form of Ras by 10-fold and
four-fold, respectively. That is, the protein geranylgeranyl transferase I
prefers to react with ras-encoded p25 fusion protein in the GDP bound form.
PMID- 10194861
TI - Effects of developmental and growth history on metamorphosis in the gray
treefrog, Hyla versicolor (Amphibia, Anura).
AB - In ecological models, the timing of amphibian metamorphosis is dependent upon
rate of larval growth, e.g., tadpoles that experience a decrease in growth rate
can initiate metamorphosis early. Recent authors have suggested that this
plasticity may be lost at some point during the larval period. We tested this
hypothesis by exposing groups of tadpoles of the gray treefrog, Hyla versicolor,
to different growth schedules. In endocrine models, metamorphosis is dependent on
thyroxine levels and thyroxine is antagonized by prolactin (amphibian larval
growth hormone), consistent with the idea that a rapidly growing tadpole can
delay metamorphosis. Thus, we also manipulated the rate of development by
supplementing or maintaining natural thyroxine levels for half of the tadpoles in
each growth treatment. All tadpoles that received thyroxine supplements
metamorphosed at the same time regardless of growth history. They also
metamorphosed earlier than tadpoles not treated with thyroxine. Tadpoles not
given thyroxine supplements metamorphosed at different times: those growing
rapidly during day 15-34 metamorphosed earlier than tadpoles growing slowly.
Growth rate before day 15 and after day 34 had no effect on metamorphic timing.
The difference in larval period between these rapidly growing tadpoles and their
sisters given thyroxine treatments was less than the same comparison for tadpoles
that grew slowly during the same period. This apparent prolactin/thyroxine
antagonism did not exist after day 34. These results are consistent with the
hypothesis of a loss of plasticity in metamorphic timing.
PMID- 10194862
TI - Precocious testicular growth in metamorphosis-arrested larvae of a salamander
Hynobius retardatus: role of thyroid-stimulating hormone.
AB - Precocious maturation of testes occurs in goitrogen-treated larvae of a
salamander Hynobius retardatus, a particular population of which has been
reported to show a neotenic reproduction in a specific environment. Similar
precocious growth of testes also was confirmed in thyroidectomized larvae in this
study. A possible involvement of thyroid-stimulating hormone (TSH) in the
precocious maturation of testes was examined in metamorphosis-arrested larvae
whose thyroid or pituitary glands had been removed surgically at embryonic stages
or which had been reared in goitrogens. The pituitary glands of both the
thyroidectomized and goitrogen-treated larvae contained extraordinarily large
number of TSH cells, which were called "thyroidectomy cells." When homogenates of
the pituitary glands from the goitrogen-treated larvae were injected into the
hypophysectomized larvae for a month, the testes grew larger than those in larvae
injected with the pituitary glands from normally metamorphosed controls. These
results are consistent with the idea that an extraordinarily high concentration
of TSH, which is induced by either thyroidectomy or goitrogen-treatment, causes
the precocious maturation of testes in the metamorphosis-arrested larvae of
Hynobius retardatus. In contrast to the precocious testicular development,
ovarian development in the metamorphosis-arrested larvae was almost identical to
that in normally metamorphosed animals within our experimental period. This also
suggests that in males the absence of thyroid hormones allows a gonadal response
that in females may require another activator in addition to or following thyroid
axis stimulation.
PMID- 10194863
TI - Plasma catecholamines and plasma corticosterone following restraint stress in
juvenile alligators.
AB - Ten juvenile alligators, mean body mass 793 g, hatched from artificially
incubated eggs and raised under controlled conditions, were held out of water
with their jaws held closed for 48 hr. An initial blood sample was taken and
further samples collected at 1, 2, 4, 8, 24, and 48 hr. Epinephrine,
norepinephrine, and dopamine were measured in plasma aliquots of 1.5 ml using
high pressure liquid chromatography with electrochemical detection.
Corticosterone was measured by radioimmunoassay. Plasma glucose was measured
using the Trinder method and plasma calcium, cholesterol, and triglycerides were
measured in an autoanalyzer. Epinephrine was about 4 ng/ml at the initial bleed,
but declined steadily to < 0.4 ng/ml by 24 hr. Norepinephrine was also about 4
ng/ml at the initial bleed, but rose to over 8 ng/ml at 1 hr, and then declined
to < 0.2 ng/ml at 24 hr. A second, but smaller increase in plasma norepinephrine
was seen at 48 hr. Plasma dopamine was low at the initial bleed (< 0.7 ng/ml),
rose to over 8 ng/ml at 1 hr, then declined to < 0.2 ng/ml. Plasma corticosterone
rose progressively for the first 4 hr, declined at 8 hr and 24 hr, then rose
again at 48 hr. Plasma glucose rose significantly by 24 hr and remained elevated
for 48 hr. Plasma calcium increased at 1, 2, and 4 hr then returned to levels not
significantly different from the initial sample at 24 and 48 hr. The white blood
cells showed changes indicating immune system suppression. By the end of the
treatment the hetorophil/lymphocyte ratio increased to 4.7. These results suggest
that handling alligators, taking multiple blood samples, and keeping them
restrained for more than 8 hr is a severe stress to the animals.
PMID- 10194864
TI - Agouti locus may influence reproduction under food deprivation in the water vole
(Arvicola terrestris).
AB - The effect of 16-hr food deprivation on day 3 and again on day 5 of pregnancy on
the fecundity of female water voles homozygous (ae/ae) or heterozygous (A/ae)
for, an allele at the Agouti (A) locus, non agouti extreme (ae) was studied. 63
A/ae females (mated to ae/ae males) produced 115 food-deprived and 115 control
pregnancies, and 52 ae/ae females (mated to A/ae males) produced 55 food-deprived
and 57 control pregnancies. Regardless of the experimental group, pregnant ae/ae
females weighed less than A/ae females. The effect of food deprivation on
fecundity depended on the Agouti-locus genotype of the female. In food-deprived
A/ae females, fecundity was diminished due to fewer successful pregnancies (P <
0.001) and lower survival of the young (P < 0.05). In food-deprived ae/ae
females, reproductive performance was not changed; a somewhat reduced rate of
successful pregnancies was compensated for by significantly increased (P < 0.002)
postnatal survival of the young. In progeny weaned from food-deprived mothers,
the frequency of A/ae females was diminished. Resistance of ae/ae females to the
negative effect of nutritional stress, and predominance of ae/ae young in progeny
produced by food-deprived mothers, may favour the maintenance of polymorphism for
the Agouti-locus in natural populations of the water vole.
PMID- 10194865
TI - Mouse embryos used as a bioassay to determine control of marsupial embryonic
diapause.
AB - Mouse blastocysts appear to be under direct inhibition from the uterine
environment, whereas no evidence of direct inhibition during diapause in the
tammar wallaby has been observed. Normally developing (day 4) and quiescent mouse
blastocysts were incubated for up to 12 hr in media supplemented with BSA,
wallaby plasma, wallaby day 0 (day of removal of pouch young; RPY), day 5, or day
10 endometrial exudates at a concentration of 2 mg/ml of protein, and analyzed
for rates of carbohydrate metabolism using fluorescence and radioisotopes. Rates
of glucose uptake and lactate production by day 4 blastocysts increase after
incubation with day 10 and day 5 wallaby exudates compared with rates by
blastocysts incubated in BSA. Pyruvate uptake increased after 8 hr irrespective
of incubation media, except for embryos incubated in day 0 exudate, which
maintained levels significantly lower than BSA-incubated embryos. Quiescent mouse
embryos displayed a high ATP/ADP ratio during diapause (1.06 +/- 0.24) which
decreased after 4 hr incubation in all media (0.42 +/- 0.05; P < 0.01) but
embryos incubated in day 0 exudate media remained at a significantly higher level
than embryos incubated in BSA. These results indicate that quiescent tammar
endometrial exudate is not capable of initiating diapause in mouse embryos at the
concentration used, but is able to slow the rate of reactivation of quiescent
blastocysts. Importantly, reactivated wallaby exudate increases mouse blastocyst
glucose metabolism and lactate production. It is possible that the quiescent
tammar endometrial environment has an inhibitory factor necessary to maintain
diapause in the tammar blastocyst.
PMID- 10194866
TI - Temporal difference between testis and ovary determinations with possible
involvement of testosterone and aromatase in gonadal differentiation in TSD
lacking lizard, Calotes versicolor.
AB - In the garden lizard, Calotes versicolor, which lacks identifiable sex
chromosomes, incubation temperature also does not have a deterministic effect on
the gender. However, the embryos reared at high temperature (33-35 degrees C)
have a shorter duration of incubation as well as gonadal differentiation. In
contrast, exogenous application of the male hormone testosterone to embryos at
ambient temperature (28 degrees C) results in almost all individuals with only
testis. Thus the testosterone treatment reverts genic females to males and
accelerates the differentiation of testis, a feature similar to the high
temperature treatment. Treatment of eggs with estradiol shows no difference from
that seen in the untreated eggs. The present series of experiments was done to
establish the "window" of testosterone sensitivity and to understand the
interaction between sex hormones and high temperature on gonadal differentiation.
The period between day 5 and 15 of embryonic development was the window period of
testosterone sensitivity for sex reversal. This period coincided with the
formation of the genital ridge and its differentiation into cortex and medulla.
Treatment of the 33 degrees C-reared embryos with testosterone resulted in
hatchlings of both the sexes, in contrast to only males at the ambient
temperature. In contrast, at the same temperature (33 degrees C), all the
dihydrotestosterone (nonaromatisable testosterone)-treated embryos hatched into
males. However, those given estradiol showed no sex bias regardless of the day of
application and the concentration of drug. Eggs were also treated with aromatase
inhibitor, CGS 16949 A, at ambient temperature and at 33 degrees C. All the 33
degrees C eggs to which the drug was given on day 25 hatched into males. These
results suggest that though high temperature has no direct effect on sex
determination in this species, it may have a stimulatory effect on aromatase
activity, leading to the conversion of the exogenously applied testosterone into
estradiol and permitting ovarian differentiation in the genic females. It also
follows from the present report that the pathway of testis formation in Calotes
versicolor is triggered much earlier, and irreversibly, than that for the ovary.
PMID- 10194867
TI - Time of ovulation in the brushtail possum (Trichosurus vulpecula) following
PMSG/LH induced ovulation.
AB - This study aimed to determine the timing of ovulation in response to a new
induced ovulation regime for the monovulatory brushtail possum (Trichosurus
vulpecula). Ovarian stimulation was achieved by a single subcutaneous injection
of 15 i.u. pregnant mare serum gonadotrophin (PMSG). This treatment resulted in
promotion of a large number (9-16) of Graafian follicles > 2 mm diameter on the
ovaries. Seventy-two hours later a single intramuscular injection of 4 mg porcine
luteinizing hormone (LH) was administered to induce ovulation. Groups of possums
were killed 24 hr post-LH injection and subsequent groups were killed at 6-hr
periods up to 48 hr later. Ovulation occurred from 30 hr to 42 hr post-LH. The
ovulatory success increased from 3% at 30 hr post-LH to 83% at 48 hr post-LH.
Oocytes were recovered primarily from the oviducts at 36 hr post-LH. Thereafter
oocytes were recovered increasingly from the uteri and by 48 hr post-LH, were
only found there. The implications of these observations for artificial breeding
in possums are discussed.
PMID- 10194868
TI - Developmental expression of the murine Prl-1 protein tyrosine phosphatase gene.
AB - The expression of the murine Prl-1 protein tyrosine phosphatase gene was examined
in normal embryos from E10.5 through E18.5. Prl-1 mRNA was detected in the brain,
neural tube, and dorsal root ganglia, and in several non-neuronal tissues,
including the skeletal system. Heart and skeletal muscle were consistently
negative. At E13.5, Prl-1 was expressed in the condensing prechondrogenic cells
of the vertebrae, whereas at E18.5, Prl-1 mRNA was localized to the hypertrophic
chondrocytes. The dynamic expression of Prl-1 during cartilage differentiation
may suggest a functional role in skeletal development.
PMID- 10194870
TI - Antibiotic treatment of adults with chest infection in general practice.
PMID- 10194869
TI - Montelukast and zafirlukast in asthma.
PMID- 10194871
TI - The place of pneumococcal vaccination.
PMID- 10194872
TI - Update on drugs for herpes zoster and genital herpes.
PMID- 10194873
TI - Co-proxamol or paracetamol for acute pain?
PMID- 10194874
TI - The structure and development of French prosodic representations.
AB - Prosody is assumed to play a crucial role during the preverbal stage of infancy,
as well as to be essential for the pragmatics of speech. Our experiments are
aimed at analyzing the production and perception of illocutionary forms. Using a
semantic neutralization procedure, the performance of children (5, 7, and 9 years
old) and adults was compared in two experiments focusing on prosodic
representations in production and perception tasks. The first experiment
investigated subjects' control of prosody in the unfolding of utterances by
studying the acoustic configurations of four illocutionary forms, two
corresponding to the linguistic mode (assertion, interrogation) and two
corresponding to the emotional mode (happiness, sadness). The second experiment
examined subjects' identification of the same illocutionary forms as above, plus
an additional form, irony, all produced by an expert speaker, using a word-by
word gating procedure. During speech production, control of the fundamental
frequency of the voice emerged earlier in childhood (5-year-olds) than control of
rhythmic parameters (7-year-olds) for the linguistic mode, whereas control of all
parameters was achieved by the age of five for the emotional mode. Children were
similar to adults with respect to the planning of intonation and they used it
right from the beginning of the sentence, which was not the case for the planning
of duration. During speech perception, only adults were able to anticipate
illocutionary forms. Taken together, the results strengthen the idea that
prosodic representations are acquired gradually during development, and they show
that pitch contour is acquired before duration parameters.
PMID- 10194875
TI - Syntactic persistence in Dutch.
AB - Three experiments are reported that showed effects of "structure priming," the
tendency to repeat syntactic structure across successive sentences. These effects
were demonstrated in a previously untested language, Dutch. All experiments
studied spoken sentence production. Importantly, pre-experimental baselines were
measured for all target structures in order to assess possible effects of
frequency on the magnitude of priming effect. We obtained priming with dative
sentences, including datives with medially placed prepositional phrases, a
sentence type not tested before. In one experiment we obtained priming effects
with passives, including passives with sentence-final verbs, which also have
never been tested before. However, we failed to obtain priming effects with
active transitives. A comparison with the baseline data suggested that priming is
not related to baseline frequency. Further, the results allowed us to draw an
empirical generalization: Structure priming is a relatively long-term event,
lasting at least several trials. The implications of these findings are
discussed.
PMID- 10194876
TI - Metrical segmentation in Dutch: vowel quality or stress?
AB - Previous experiments using a word-spotting task suggest that English listeners
use metrically strong syllables to segment continuous speech into discrete words
(Cutler & Norris, 1988). The present study is concerned with this metrical
segmentation strategy in Dutch. Although Dutch and English share general metrical
properties, they differ in ways that may affect segmentation. First, the acoustic
cues for metrically strong syllables are less salient in Dutch than in English;
hence a metrical segmentation strategy is less likely to be applied by Dutch
listeners. Second, vowel quality depends less on metrical structure in Dutch than
in English; hence segmentation in Dutch is presumably triggered by other acoustic
cues, namely, those related to stress. Experiment 1 shows that stress strongly
affects Dutch listeners' ability and speed in spotting Dutch monosyllabic words
in disyllabic nonwords. Experiment 2, however, finds the same stress effect when
only the target words are presented, without a subsequent syllable triggering
segmentation. A third experiment shows a small effect of vowel quality on error
scores, but not on latencies. These results suggest that Dutch listeners do not
apply a metrical segmentation strategy. The discrepancy between the two languages
suggests that segmentation strategies may depend on language-specific
regularities in the phonology and in the lexicon.
PMID- 10194877
TI - When can listeners detect disfluency in spontaneous speech?
AB - Three experiments investigated listeners' ability to detect disfluency in
spontaneous speech. All employed gated word recognition with judgments of
disfluency for spontaneous utterances containing disfluencies and for three kinds
of fluent control utterances from the same six speakers: repetitions of corrected
recordings of original disfluent items, spontaneous fluent utterances loosely
matched in structure to the disfluent items, and repetitions of those spontaneous
fluent items. In Experiment 1, 120 stimuli were word-level gated and presented to
20 subjects for word identification and for judgments on whether the utterance
was about to become disfluent. Listeners were unable to predict disfluency
reliably. New subjects (N = 20, 43) judged whether the same utterances had
already become disfluent at each word gate in Experiment 2 or at each 35 ms gate
in Experiment 3. Subjects reliably detected existing disfluencies during the
first word gate after the interruption and before they recognized the word.
Though more common around disfluencies than at similar points in controls,
failures of word identification were not reliably associated with detection.
Results are discussed in the light of computational models of disfluency
detection.
PMID- 10194878
TI - [Effect of methods of sterilization on thermoplastics with special reference to
modified surfaces].
AB - For materials intended for use in the medical setting their sterilizability is an
indispensable prerequisite. In the case of most polymers the usual sterilization
methods result in changes that even extend to cleavage of the polymer chains. A
particular problem in this respect are the surfaces modified for improved
biocompatibility investigated in the present study, which are characterised by
enlarged contact areas. For this reason, possible changes to three different
thermoplastics commonly used for medical applications (polyethylene,
thermoplastic polyurethane, polycarbonate) were investigated. Steam, gas and
radiation were used for sterilization. Tensile tests were employed to identify
changes in mucosal characteristics caused by different sterilization techniques
irrespective of the surface modification. Sterilization-related changes to the
structure of the modified surfaces were investigated with the scanning electron
microscope (SEM). Differential thermo analysis (DTA) was used to determine
changes in the thermal characteristics of the plastics. Clear tendencies with
regard to the behaviour of the plastics after sterilization with various
techniques were found. A general statement about the compatibility of plastic
materials with a specific sterilization method is not possible on the basis of
this study. For every new polymeric product used for medical purposes, the
characteristics required must first be defined and compliance with the
permissible variations of these characteristics investigated for each of the
various sterilization techniques available.
PMID- 10194879
TI - [Standardized testing of bone implant surfaces with an osteoblast cell culture
system. II. Titanium surfaces of different degrees of roughness].
AB - The effect of titanium surfaces with different degrees of roughness on osteoblast
proliferation and differentiation was investigated using a standardised cell
culture system. Human foetal osteoblasts (hFOB 1.19) were cultured on polished
(Ti pol), sandblasted (Ti sb) and sandblasted/heat treated (Ti sb-ht) titanium
surfaces for 17 days. Cell culture quality polystyrene (Ps) was used as a
control. Cell number and viability were determined for assessment of
proliferation. Alkaline phosphatase activity, collagen I and osteocalcin
production were measured as parameters for osteoblast differentiation. In the
early phase, higher proliferation values were measured on Ti pol. However, on Ti
sb and Ti sb-ht higher proliferation was found in the late phase. The activity of
the early differentiation marker alkaline phosphatase was higher on Ti pol. No
differences were seen for the late differentiation parameters collagen I and
osteocalcin. The test system permits the influence of the surface structure on
the dynamics of the osteoblast development cycle to be determined. The larger
surface area of rough materials leads to an initially delayed, but then prolonged
cell proliferation. This model correlates with recent in vivo findings, and
confirms the use of rough surfaces for implants in direct contact with bone, even
at the cellular level.
PMID- 10194880
TI - Design of an EEG-based brain-computer interface (BCI) from standard components
running in real-time under Windows.
AB - An EEG-based brain-computer interface (BCI) is a direct connection between the
human brain and the computer. Such a communication system is needed by patients
with severe motor impairments (e.g. late stage of Amyotrophic Lateral Sclerosis)
and has to operate in real-time. This paper describes the selection of the
appropriate components to construct such a BCI and focuses also on the selection
of a suitable programming language and operating system. The multichannel system
runs under Windows 95, equipped with a real-time Kernel expansion to obtain
reasonable real-time operations on a standard PC. Matlab controls the data
acquisition and the presentation of the experimental paradigm, while Simulink is
used to calculate the recursive least square (RLS) algorithm that describes the
current state of the EEG in real-time. First results of the new low-cost BCI show
that the accuracy of differentiating imagination of left and right hand movement
is around 95%.
PMID- 10194881
TI - [Classification of cytological smears of the cervix with neuronal methods].
AB - BACKGROUND: Cytological smears obtained from the cervix are routinely examined
under the microscope as part of screening programs for the early detection of
cervical cancer. The aim of the present study was to investigate whether a simple
feature extraction approach using only standard image processing techniques
combined with a neural classifier would lead to acceptable results that might
serve as a starting point for the development of a fully automated screening
system. MATERIALS AND METHODS: Gray-value images of 106 cervical smears (512 x
512 pixels) divided into two groups--inconspicuous (57) and atypical (49)--by an
experienced pathologist on the basis of the original smears were employed to
evaluate the method. From these images, 31 features quantifying properties of
either the cell nucleus or the cytoplasm were extracted. These features were
categorized with three different architectures of a neural classifier: learning
vector quantization (LVQ), multilayer perceptron (MLP) and a single perceptron.
CONCLUSIONS: The results show a reclassification accuracy of about 91% for all
three algorithms. Sensitivity was uniform at approximately 78%, and specificity
varied between 75% and 91% in the leave-one-out evaluation. These very good
results provide strong encouragement for further studies involving PAP scores and
colour images.
PMID- 10194882
TI - [Fiber optic sensor technology in the endotracheal tube].
AB - The measurement of individual respiratory parameters in the vicinity of the lungs
remains an unresolved problem in the areas of anesthesia and intensive care
medicine. New technologies such as fibreoptic technology, which meet the extreme
demands of medical sensor applications, and their innovative potential as a basis
for the development of marketable products, appear promising. This is illustrated
by the fundamental principles developed for a sensor-armed tracheal tube for on
line monitoring of ventilated patients.
PMID- 10194883
TI - Gender differences on Internet cancer support groups.
AB - The role of community-based cancer support groups (CSGs) in helping people cope
with cancer is well known. Recently, online CSGs have become a viable alternative
to traditional CSGs. The purposes of this study were to determine if categories
of responses on Internet cancer support groups (ICSGs) differ when the majority
of the participants were of a single gender, and whether response categories seen
on gender-specific ICSGs were different than those on ICSGs used equally by men
and women. A line-by-line analysis of postings on prostate, breast, and mixed
ICSGs were analyzed and responses categorized. Four categories (information
giving/seeking; encouragement/support; personal opinion; and personal experience)
accounted for approximately 80% of responses across the groups. Information
giving/seeking was ranked first in the prostate group, and personal experience
took priority in the breast group. Men were more than twice as likely to give
information and women more than twice as likely to give encouragement and
support. One category (prayer), identified in the mixed group, was lacking in the
prostate and breast groups, and an activism category was added to the prostate
group. Categorical responses differed by gender (chi 2 = 79.40, P < .0001).
Attention should be given to facilitating the entry of underserved groups into
ICSGs. Future research should explore the relationship between ICSG membership
and variables such as depression, survival time, and quality of life.
PMID- 10194885
TI - The copyright quagmire on the Internet.
AB - The use of the Internet is expanding exponentially. More and more individuals are
gaining access to the information structure once limited to universities and
military applications. The ease of access and distribution of materials were
never envisioned by the authors of the Berne Convention, which outlined original
international copyright laws. Along with greater freedom experienced through the
Internet and the creative exchange of ideas comes a quagmire of legal issues.
This article identifies the issues currently being discussed by world leaders in
copyright law and the implications to nursing education as it expands and
explores the use of the Internet for educational purposes.
PMID- 10194886
TI - Interactive videodisc instruction with undergraduate nursing students using
cooperative learning strategies.
AB - This study was conducted to explore the use of interactive videodisc instruction
(IVDI) with cooperative learning strategies. Baccalaureate students in their
junior year were assigned to one of three types of groups based on prenursing
grade point average: homogeneous average achievement, homogeneous high
achievement, and heterogeneous mixed achievement students. Groups of three to
five students viewed a lesson related to auscultation of heart sounds using IVDI
and were videotaped throughout the lesson. There were no significant differences
among the groups in their interaction frequencies, cooperativeness, or
achievement on the group posttest completed immediately after viewing the lesson.
Homogeneous high achievement students scored significantly higher than the other
two groups on the individual posttests given 2 weeks after viewing the lesson.
However, all three groups had very low scores. Several themes emerged related to
management of the lesson. A majority of the students without previous IVDI
experience had difficulty accessing and proceeding through the lesson: fill-in
the-blank questions posed by the lesson often were frustrating to the students,
students in groups had difficulty reading the touch screen monitor, a large
number of students attempted to locate the cardiac valves on themselves or other
group members, and male students tended to distance themselves from each other.
In this study, students needed more orientation to the computer equipment and to
cooperative learning strategies. When using IVDI with inexperienced students,
faculty should be certain that technical assistance is available throughout the
lesson.
PMID- 10194884
TI - Designing an information technology application for use in community-focused
nursing education. Nightingale Tracker Field Test Nurse Team.
AB - Changes in healthcare are highlighting the need for nurse educators to include
more community-focused clinical experiences in the nursing curriculum. Because
community experiences often require students to travel to clinics and patients'
homes at multiple distant sites, nurse educators are concerned about how to best
supervise their students and maintain reliable communication links. In light of
these needs, FITNE (formerly the Fuld Institute for Technology in Nursing
Education) undertook a 3-year information technology research and development
project known as the Nightingale Tracker. The design for the Nightingale Tracker
included activities aimed toward analyzing the unique communication needs faced
by practitioners in community settings. It incorporated multiple forms of user
input, including requirements-gathering focus groups, nurse educator surveys, and
feedback from two user tests. Subject feedback from using Tracker prototypes in
the field was invaluable in the design of the final product.
PMID- 10194888
TI - Leadership for nursing.
PMID- 10194887
TI - Partners ... in time.
PMID- 10194889
TI - Impact of federal funding increase for research.
PMID- 10194890
TI - Establishing a clinical track for faculty--feat or folly?
PMID- 10194891
TI - State and federal health priorities.
PMID- 10194892
TI - Evidence-based nursing practice: both state of the art in general and specific to
pressure sores.
AB - The importance of research-based practice in nursing has been frequently
stressed, and a number of nursing studies have been conducted whose results
enable nursing to improve knowledge and practice. This study reports a literature
review in which the current status of knowledge and research utilization with
regard to pressure sores is described. This review first gives an overview of
studies on knowledge utilization in general and shows that the spontaneous
diffusion of knowledge is inappropriate. Furthermore, an overview of planned
research utilization activities focusing on pressure sore prevention and
treatment in nursing is presented. The results of these studies show that planned
research utilization activities performed in individual organizations lead to
positive outcomes in almost all cases. Therefore, it could be concluded that
implementing planned research utilization activities in individual health care
institutions seems to be an effective strategy to decrease pressure sore
incidence and prevalence rates.
PMID- 10194893
TI - Gerontological nursing content in baccalaureate nursing programs: findings from a
national survey.
AB - Given the prevalence of elderly people in the health care system, it behooves the
nursing community to assure that every nurse graduating from a baccalaureate
nursing program has a defined level of competency in care of the elderly. To
accomplish this, it is necessary to establish a baseline of the current status of
geriatric content in the baccalaureate curriculum. This article provides such
baseline data using the findings of a national study of geriatrics in
baccalaureate nursing programs. The study, conducted in 1997, was distributed to
the universe of baccalaureate nursing programs (n = 598). The findings are based
on a respondent pool of 480 programs (80.3 per cent response rate). The survey
covered a range of educational topics, including curriculum, content, faculty
preparation, and how programs define their needs for further curriculum and
faculty development. The data analysis included the identification of
baccalaureate nursing programs with exemplary offerings in geriatric care.
Finally, in the discussion section, recommendations are advanced for the full
integration of geriatric content into baccalaureate nursing programs.
PMID- 10194894
TI - High school students of color tell us what nursing and college mean to them.
AB - Excerpts from application essays of urban public high school sophomores of color
enrolled in Choose Nursing!, a precollegiate nursing career development program,
illustrate their clear, insightful, and positive perceptions of nursing. The
hospital-based program received 187 applications over a 4-year period. It
enrolled 61 students and graduated 40, all of whom matriculated at 4-year
colleges; 36 declared a nursing major. Based on application and other student
essays, as well as data used for formative evaluation, the author suggests that
efforts to recruit urban students of color for baccalaureate nursing education
should be school focused and built on the positive perceptions and strong
interest in nursing and collegiate education held by many students. Promising
ways to engage and support interested students while they still have time to meet
college and nursing prerequisites are integrated within the discussion, as is the
value of hands-on experience in a "nursing" role in motivating students to
persist in reaching their goals.
PMID- 10194895
TI - Nurses' unique roles in randomized clinical trials.
AB - Nurses are in an ideal position to promote patients' awareness of the role played
by clinical trials in the advancement of health science and the subsequent
improvement of patient care. The history of clinical trials and the four phases
of clinical trials are described. Nurses' professional roles in clinical trial
participation, such as helping the patient to identify open clinical trials and
acting as clinical interpreter and patient advocate during the patient's
participation in a trial, are detailed. Professional considerations that must be
addressed by the nurse are reviewed and include ensuring that the trial has
received approval from an Institutional Review Board for the participation of
human subjects; that the responsibilities of participation are congruent with the
nurse's personal values and workplace obligations; and that once engaged, the
nurse can make the commitment to sustain participation in the trial. Most
important, the nurse must keep the patient's needs and values uppermost in mind
during the evaluation of potential clinical trials. Nurses have a critical role
to play in the promotion of clinical trials, the recruitment of patients for
clinical trial participation, the education of the patient and family, and the
clinical care and support of patients throughout their participation in clinical
trials.
PMID- 10194896
TI - A partnership model of distance education: students' perceptions of connectedness
and professionalization.
AB - This article describes a partnership model of distance education for a master's
nursing program in a midwestern state and an evaluation that assessed students'
perceptions of professionalization and connectedness in the program. Students at
the originating and distance sites were asked to complete evaluations at the end
of each course. Connectedness and professionalization were measured using rated
satisfaction with three modes of contact for each item. Results indicated that
students at the distance site had a significantly higher overall level of
satisfaction with interactive television (ITV) and experienced high levels of
connectedness and professionalization through the ITV courses. However, among the
three modes of connectedness, students at the distance site rated satisfaction
with contact with same-site students as the highest, followed by contact with the
instructor. Students also perceived that their professional identity increased
through the three modes, particularly for contact with same-site peers at the
distance site and for contact with instructors at both sites. Recommendations for
faculty and student responsibilities are provided to ensure a positive learning
environment.
PMID- 10194897
TI - Enhancing math competency of baccalaureate students.
AB - The result of a 4-year effort to study and institute changes in Baylor University
School of Nursing's baccalaureate (BSN) students' math competencies was
successful. The evolution of the current math competency process is detailed. By
identifying at-risk, entry-level students through math examination in the junior
I semester and each semester in the program, individual clinical faculty can
customize the teaching-learning experience for students. Students who need more
help than a clinical instructor has available, which is documented by semester
examination failure, benefit from taking a 1-hour medication administration
course before graduating from the BSN program. Insights and suggestions are
offered for other schools encountering this problem.
PMID- 10194898
TI - Certification and regulation of advanced practice nurses. American Association of
Colleges of Nursing.
PMID- 10194899
TI - [The intensive care unit is a hot zone for antibiotic resistance].
PMID- 10194900
TI - [The instruction for interns has many shortages].
PMID- 10194901
TI - [It is more important to warn practitioners about metal exposure than to train
"mouth specialists"].
PMID- 10194902
TI - [Public health research is a medical issue!].
PMID- 10194903
TI - [Safety belts as a traffic safety requirement].
PMID- 10194904
TI - [Medical ethics as individual psychology].
PMID- 10194905
TI - [What is the truth about sex distribution?].
PMID- 10194906
TI - [Who with acute otitis is to be treated with antibiotics?].
PMID- 10194907
TI - [It is not easy to examine the causes of fainting. Vasovagal syncope is mostly
not dangerous, cardiac syncope is potentially life-threatening].
AB - Of the approximately 30 per cent of the population who are afflicted with syncope
at some time of life, 30 per cent will relapse. Despite extensive investigation,
no specific cause is identified in about one third of cases. Although some
episodes of syncope, e.g. cardiovascular syncope, are benign and self-limiting,
others such as mechanical cardiac syncope and arrhythmogenic syncope are
associated with considerable mortality. The article consists in a review of
available data on differential diagnostic evaluation and treatment with special
emphasis on case history.
PMID- 10194908
TI - [Vaccination against type 1 diabetes at the clinical trial stage].
AB - The occurrence of type I diabetes is associated with autoimmunity against
insulin, glutamate decarboxylase (GAD65) and the transmembrane protein IA-2.
Experiments in the spontaneously diabetic NOD mouse and the BB rat have shown
early autoantigen treatment to confer protection from diabetes. The question
remains of whether human type I diabetes can be prevented by autoantigen
'vaccination'.
PMID- 10194909
TI - [The elderly should be vaccinated against pneumococci].
AB - Invasive pneumococcal diseases are associated with substantial mortality in the
elderly. The incidence of such diseases, particularly that of bacteraemic
pneumococcal pneumonia, has increased in Sweden during the past decade. At the
same time, there is a growing problem with beta-lactam-resistant and
multiresistant pneumococci in many nearlying countries. Although pneumococcal
vaccine probably provides only limited protection against pneumococcal pneumonia
in the elderly, it yields approximately 70 per cent protection against invasive
pneumococcal disease. Pneumococcal vaccination should therefore be recommended to
all those 65 years old and above, and a nationwide strategy developed to
implement good coverage in the age group.
PMID- 10194910
TI - [When the expected child dies. Both emotional and practical support is important
for the women affected].
AB - The results of a nationwide population-based epidemiological study of 636 women
showed the majority of those who lost a child prenatally in 1991 to have been
satisfied with the care they received. After a stillbirth it is beneficial to
create a peaceful, supportive atmosphere in which the woman may spend as much
time with her stillborn child as she wishes. Access to tangible reminders of the
child reduces the risk of anxiety. The findings suggest that delivery should be
induced as soon as the woman desires. Almost all the women stressed the
importance of obtaining an adequate explanation of the child's death, in order to
come to terms with their loss.
PMID- 10194911
TI - [A successful combination of PTCA and bypass surgery].
PMID- 10194912
TI - [Torsion of the hydatid of Morgagni--a hereditary disease? The most common cause
of acute scrotum in children].
PMID- 10194913
TI - [Medical education in the Netherlands. A great deal of general practice].
PMID- 10194914
TI - [New standards for infusion pumps--with shortages physicians should know about].
PMID- 10194915
TI - [Resources are still in short supply for mentally disabled criminals].
PMID- 10194916
TI - [Hallucinations after infusion of large doses of corticosteroids. A well-known
and unusually well-reported side effect].
PMID- 10194917
TI - [Cortisone--a Mene tekel?].
PMID- 10194918
TI - [Cognitive attitude is applicable even in general medicine].
PMID- 10194920
TI - [Electronic version of the Fass is also considered to be reliable].
PMID- 10194919
TI - [Criticism against the SBU coronary vessel study reflects a negative attitude
toward scrutiny].
PMID- 10194921
TI - Exponential growth in age-structured two-sex populations.
AB - We consider a continuous age-structured two-sex population model which is given
by a semilinear system of partial differential equations with nonlocal boundary
conditions and is a simpler case of Fredrickson-Hoppensteadt model. The non
linearity is introduced by a source term, called from its physical meaning, the
marriage function. The explicit form of the marriage function is not known;
however, there is an understanding among the demographers about the properties it
should satisfy. We have shown that the homogeneity property of the non-linearity
leads to the fact that the system supports exponentially growing persistent
solutions using a general form of the marriage function and its properties. This
suggests that the model can be viewed as a possible extension of the one-sex
stable population theory to monogamously mating two-sex populations.
PMID- 10194922
TI - Individual based modeling and parameter estimation for a Lotka-Volterra system.
AB - Stochastic component, inevitable in biological systems, makes problematic the
estimation of the model parameters from a single sequence of measurements,
despite the complete knowledge of the system. We studied the problem of parameter
estimation using individual-based computer simulations of a 'Lotka-Volterra
world'. Two kinds (species) of particles--X (preys) and Y (predators)--moved on a
sphere according to deterministic rules and at the collision (interaction) of X
and Y the particle X was changed to a new particle Y. Birth of preys and death of
predators were simulated by addition of X and removal of Y, respectively,
according to exponential probability distributions. With this arrangement of the
system, the numbers of particles of each kind might be described by the Lotka
Volterra equations. The simulations of the system with low (200-400 particles on
average) number of individuals showed unstable oscillations of the population
size. In some simulation runs one of the species became extinct. Nevertheless,
the oscillations had some generic properties (e.g. mean, in one simulation run,
oscillation period, mean ratio of the amplitudes of the consecutive maxima of X
and Y numbers, etc.) characteristic for the solutions of the Lotka-Volterra
equations. This observation made it possible to estimate the four parameters of
the Lotka-Volterra model with high accuracy and good precision. The estimation
was performed using the integral form of the Lotka-Volterra equations and two
parameter linear regression for each oscillation cycle separately. We conclude
that in spite of the irregular time course of the number of individuals in each
population due to stochastic intraspecies component, the generic features of the
simulated system evolution can provide enough information for quantitative
estimation of the system parameters.
PMID- 10194923
TI - A diffusive-convective model for the dynamics of population-toxicant
interactions: some analytical and numerical results.
AB - In this paper we consider a diffusive-convective model for the dynamics of a
population living in a polluted environment. Threshold results are given
concerning the effect of the toxicant on the living population. Some analytic
results are proved and numerical experiments give suggestions in more general
cases.
PMID- 10194924
TI - Two models for competition between age classes.
AB - We consider two lumped age-structured models of juvenile against adult
competition, one of which is a compartmental ordinary differential equation (ODE)
model and one of which is a system of ODEs with delay derived from the McKendrick
partial differential equation (PDE) model. Existence and stability of positive
equilibria and existence of oscillatory solutions of both models are studied.
Using a competition parameter, which measures the intra-specific competition, we
investigate the effects of the competitive interactions between juveniles and
adults on the dynamics of the population for both models. We find that these
effects are different for the two models and discuss the differences from the
modeling perspective. The discussion reveals an interesting relation between the
length of the maturation period and the vital rates' dependence on the
competition parameter.
PMID- 10194925
TI - A discrete model with density dependent fast migration.
AB - The aim of this work is to develop an approximate aggregation method for certain
non-linear discrete models. Approximate aggregation consists in describing the
dynamics of a general system involving many coupled variables by means of the
dynamics of a reduced system with a few global variables. We present discrete
models with two different time scales, the slow one considered to be linear and
the fast one non-linear because of its transition matrix depends on the global
variables. In our discrete model the time unit is chosen to be the one associated
to the slow dynamics, and then we approximate the effect of fast dynamics by
using a sufficiently large power of its corresponding transition matrix. In a
previous work the same system is treated in the case of fast dynamics considered
to be linear, conservative in the global variables and inducing a stable
frequency distribution of the state variables. A similar non-linear model has
also been studied which uses as time unit the one associated to the fast dynamics
and has the non-linearity in the slow part of the system. In the present work we
transform the system to make the global variables explicit, and we justify the
quick derivation of the aggregated system. The local asymptotic behaviour of the
aggregated system entails that of the general system under certain conditions,
for instance, if the aggregated system has a stable hyperbolic fixed point then
the general system has one too. The method is applied to aggregate a
multiregional Leslie model with density dependent migration rates.
PMID- 10194926
TI - Variables aggregation in a time discrete linear model.
AB - In this work we extend approximate aggregation methods to deal with a very
general linear time discrete model. Approximate aggregation consists in
describing some features of the dynamics of a general system in terms of the
dynamics of a reduced system governed by a few global variables. We present a
time discrete model for a structured population (i.e., the population is
subdivided in subpopulations) in which we can distinguish two processes of a
general nature and whose corresponding time scales are very different from each
other. We transform the general system to make the global variables appear and
obtain the reduced system. These global variables are, for each subpopulation, a
certain linear combination of the corresponding state variables. We show that,
under quite general conditions, the asymptotic behavior of the reduced system can
be known in terms of the corresponding behavior for the reduced system. The
general method is applied to aggregate a multiregional Leslie model in which the
demographic process is supposed to be fast with respect to migration.
PMID- 10194927
TI - On the numerical integration of non-local terms for age-structured population
models.
AB - We formulate explicit second-order finite difference schemes for the numerical
integration of non-linear age-dependent population models. These methods have
been designed by means of a representation formula for the theoretical solution
of the integro-differential equation joint with open quadrature formulae for the
numerical approximation of non-local terms. The schemes are analyzed and some
numerical experiments are also reported in order to show numerically their
accuracy.
PMID- 10194928
TI - Numerical schemes for size-structured population equations.
AB - We formulate schemes for the numerical solution of size-dependent population
models. Such schemes discretize size by means of a natural grid, which introduces
a discrete dynamics. The schemes are analysed and optimal rates of convergence
are derived. Some numerical experiments are also reported to demonstrate the
predicted accuracy of the schemes.
PMID- 10194929
TI - Behavioral choices based on patch selection: a model using aggregation methods.
AB - The aim of this work is to study the influence of patch selection on the dynamics
of a system describing the interactions between two populations, generically
called 'population N' and 'population P'. Our model may be applied to prey
predator systems as well as to certain host-parasite or parasitoid systems. A
situation in which population P affects the spatial distribution of population N
is considered. We deal with a heterogeneous environment composed of two spatial
patches: population P lives only in patch 1, while individuals belonging to
population N migrate between patch 1 and patch 2, which may be a refuge.
Therefore they are divided into two patch sub-populations and can migrate
according to different migration laws. We make the assumption that the patch
change is fast, whereas the growth and interaction processes are slower. We take
advantage of the two time scales to perform aggregation methods in order to
obtain a global model describing the time evolution of the total populations, at
a slow time scale. At first, a migration law which is independent on population P
density is considered. In this case the global model is equivalent to the local
one, and under certain conditions, population P always gets extinct. Then, the
same model, but in which individuals belonging to population N leave patch 1
proportionally to population P density, is studied. This particular behavioral
choice leads to a dynamically richer global system, which favors stability and
population coexistence. Finally, we study a third example corresponding to the
addition of an aggregative behavior of population N on patch 1. This leads to a
more complicated situation in which, according to initial conditions, the global
system is described by two different aggregated models. Under certain conditions
on parameters a stable limit cycle occurs, leading to periodic variations of the
total population densities, as well as of the local densities on the spatial
patches.
PMID- 10194930
TI - Resistance of a food chain to invasion by a top predator.
AB - We study the invasion of a top predator into a food chain in a chemostat. For
each trophic level, a bioenergetic model is used in which maintenance and energy
reserves are taken into account. Bifurcation analysis is performed on the set of
nonlinear ordinary differential equations which describe the dynamic behaviour of
the food chain. In this paper, we analyse how the ability of a top predator to
invade the food chain depends on the values of two control parameters: the
dilution rate and the concentration of the substrate in the input. We investigate
invasion by studying the long-term behaviour after introduction of a small amount
of top predator. To that end we look at the stability of the boundary attractors;
equilibria, limit cycles as well as chaotic attractors using bifurcation
analysis. It will be shown that the invasibility criterion is the positiveness of
the Lyapunov exponent associated with the change of the biomass of the top
predator. It appears that the region in the control parameter space where a
predator can invade increases with its growth rate. The resulting system becomes
more resistant to further invasion when the top predator grows faster. This
implies that short food chains with moderate growth rate of the top predator are
liable to be invaded by fast growing invaders which consume the top predator.
There may be, however, biological constraints on the top predator's growth rate.
Predators are generally larger than prey while larger organisms commonly grow
slower. As a result, the growth rate generally decreases with the trophic level.
This may enable short food chains to be resistant to invaders. We will relate
these results to ecological community assembly and the debate on the length of
food chains in nature.
PMID- 10194931
TI - Rheodynamic model of cardiac pressure pulsations.
AB - To analyse parametrically (in terms of the qualitative theory of dynamical
systems) the mechanical influence of inertia, resistance (positive and negative),
elasticity and other global properties of the heart-muscle on the left
ventricular pressure, an active rheodynamic model based on the Newtons's
principles is proposed. The equation of motion of the heart mass centre is
derived from an energy conservation law balancing the rate of mechanical (kinetic
and potential) energy variation and the power of chemical energy influx and
dissipative energy outflux. A corresponding dynamical system of two ordinary
differential equations is obtained and parametrically analysed in physiological
conditions. As a result, the following main conclusion is made: in physiological
norm, because of the heart electrical activity, its equilibrium state is unstable
and around it, mechanical self-oscillations emerge. In case the electrical
activity ceases, an inverse phase reconstruction occurs during which the unstable
equilibrium state of the system becomes stable and the self-oscillations
disappear.
PMID- 10194932
TI - Role of the dispersion of refractoriness on cardiac reentries.
AB - We used computer simulation to study the possible role of the dispersion of
cellular coupling, refractoriness or both, in the mechanisms underlying cardiac
arrhythmias. Local ischemia was first assumed to induce cell to cell dispersion
of the coupling resistance (case 1), refractory period (case 2), or both (case
3). Our numerical experiments based on the van Capelle and Durrer model showed
that vortices could not be induced. On the other hand, with cellular properties
dispersed in a patchy way within the ischemic zone, a single activation wave
could give rise to abnormal activities. This demonstrates the stability of the
wave front under small inhomogeneities. Probabilities of reentry, estimated for
the three cases cited above showed that a severe alteration of the coupling
resistance may be an important factor in the genesis of reentry. Moreover, use of
isochronal maps revealed that vortices were both stable and sustained with an
alteration of the coupling alone or along with a reduction of the action
potential duration. Conversely, simulations with reduction of the refractoriness
alone, inducing only transient patterns, could exhibit functionally determined
reentries.
PMID- 10194933
TI - Dynamics of the inducing signal for the SOS regulatory system in Escherichia coli
after ultraviolet irradiation.
AB - SOS response in Escherichia coli is induced by various DNA-damaging treatments,
for example by ultraviolet irradiation, to help a cell to recover from the
damage. During induction of the SOS regulatory system, generation of the inducing
signal for the system is the early step. In the present study a model for
quantitative description of the signal dynamics is developed. We derive the
inducing signal, in terms of concentration of single-stranded DNA, as a function
of time since the moment of ultraviolet irradiation. Simulation of the signal
level after irradiation with two doses of 5 and 20 J m-2 is presented. This
provides quantitative description of the event that controls various cellular
physiological reactions induced in the course of the SOS response. The dynamics
of the signal level are then used as an input for a dynamical equation
description of the SOS regulatory system that we proposed earlier. This allows
for a quantitative analysis of the subsequent step in the SOS induction: cleavage
of LexA protein, a negative regulator of the SOS system. The model is verified
against available experimental data for LexA protein level in ultraviolet
radiation-induced Escherichia coli cells.
PMID- 10194934
TI - Non-linear analysis of the rhythmic activity in rodent brains.
AB - This paper discusses the employment of non-parametric non-linear prediction
algorithms to investigate non-linear dynamics in the rhythmic brain activity of
rats. Three algorithms (Sugihara-May Simplex, K-neighbour and Casdagli's) were
tested yielding similar prediction results which--when subject to a suitable
bootstrap based t-tests--revealed that the theta waves recorded in rat brains
cannot have their intrinsic non-linearity dismissed at a significance of 0.05.
PMID- 10194935
TI - Testing procedures for non-stationarity and non-linearity in physiological
signals.
AB - Most of the physiological signals (EEG, ECG, blood flow, human gait, etc.)
characterize by complex dynamics including both non-stationarities and non
linearities. These time series resemble red noise with long-range correlation and
1/(f beta) power spectrum. A question arises as to how to distinguish the
characteristics of the process underlying the signal dynamics from the properties
of the observed time series. The classical methods to determine possible non
linear (chaotic) dynamics (e.g. correlation dimension) often fail in such signals
because of relatively short data records containing stochastic components and non
stationarities. We report an application of several approaches, aimed at (1)
determining of the non-stationarities in the signals and (2) testing whether non
linear dynamics exists. Assessment of the intrinsic correlation properties of the
dynamic process and distinguishing the same from external trends was performed
using singular spectra and detrended fluctuation analysis. The existence of non
linear dynamics was tested by correlation dimension (modified algorithm of re
embedding) and by correlation integrals of real and surrogate data. The
correlation integrals of real signal and surrogate data sets were statistically
compared using Kolmogorov-Smirnov (K-S) test. The procedures were tested on EEG
and laser-Doppler (LD) blood flow. Our suggestion is that no one approach taken
alone is the best for our aims. Instead, a battery of methods should be used.
PMID- 10194936
TI - A comparative study of processing simulated and experimental data in elastic
laser light scattering.
AB - The intensity of the laser light scattered by a suspension of biological
particles undergoing Brownian motion contains information about their size
distribution function and optical properties. We used several methods
(implemented in MathCAD programs), including a new one, to invert the Fredholm
integral equation of the first kind, which represents the angular dependence of
the elastic scattering of light. The algorithms were first tested on different
sets of simulated data. Experimental data were obtained using biological samples
and an experimental arrangement which are briefly described. We study the
stability of the inversion procedures relative to the noise levels, and compute
the first two moments of the retrieved size distribution function. A comparison
of the results corresponding to simulated and experimental data is done, to
select the best processing algorithm.
PMID- 10194937
TI - Determination of erythrocyte aggregation.
AB - One of the most common health criteria--erythrocyte sedimentation rate (ESR)--is
considered in the paper. It is shown that the simple model presented, based on
the generalized Stokes formula, the blood volume conservation law, and the
Smoluchowski theory of particles coagulation, makes it possible, on the basis of
experimentally recorded sedimentation curves, to identify quantitatively the
values of the essential physical parameters of the coupled processes of
erythrocyte aggregation and sedimentation. The analytical solution of
Smoluchowski equation is used to evaluate the sedimentation and aggregation rate
constants. The problem of determining the erythrocyte aggregation rate (EAR) is
transformed to a minimization task in which only the experimental results for ESR
are needed. Experimentally ESR is measured accurately enough by using an
equipment set up just for the purpose. This method of identification could be
used as a diagnostic test in hematological laboratories.
PMID- 10194938
TI - Non-linear qualitative signal processing for biological systems: application to
the algal growth in bioreactors.
AB - We present in this paper a qualitative method to validate and monitor the
structure of a non-linear model with respect to experimental data, under some
hypotheses. This method is broadly independent of the analytical formulation of
the model, and depends only on the qualitative structure (the signs of the
Jacobian matrix). The temporal sequences of the extrema of a filtered
experimental signal are compared with the transitions allowed by a graph. In
particular, we show that the usual moving average of the outputs follows this
transition graph. We apply this method to compare models of algal growth in a
bioreactor with experimental data.
PMID- 10194939
TI - [Galenic aspects and therapy of chronic inflammatory bowel diseases.
Introduction].
PMID- 10194940
TI - [Concept of control of galenic properties in oral administration of drugs].
AB - The pharmaceutical and biopharmaceutical development of drug preparations
comprehends the transformation of a drug in an applicable drug preparation with
optimal efficacy, safety and acceptance. Thus, a drug delivery system has to be
developed that controls the onset, the duration and the intensity of the expected
effect. Depending on the specific drug properties and to the special objectives
different controlling principles have to be selected. These are for example
delayed release (salivaresistance, gastroresistance), slow release, release in
distinct regions of the gastrointestinal tract and accelerated release.
PMID- 10194941
TI - ["Targeted delivery" in the gastrointestinal tract].
AB - Drug delivery to the intestine has become attractive to researchers with the main
interest in the delivery of peptide drugs to the large intestine and the
treatment of colonic diseases. There are currently 4 strategies that are pursued
to reach colon specificity: 1. by relying on the pH difference between the small
and the large intestine; 2. by exploiting the enzymatic activity of the colonic
microflora; 3. by relying on the relatively constant small intestinal transit
time and 4. by taking advantage of the increase of the luminal pressure in the
colon due to strong peristaltic waves. Drug delivery to the small intestine may
be achieved by pH-controlled and time-controlled drug release mechanisms.
Diffusion-controlled systems allow drug delivery over the entire gastrointestinal
tract.
PMID- 10194942
TI - [Effect of euddragit and ethylcellulose coatings. A short review of pH and
diffusion controlled drug delivery].
AB - In this short review the fundamental differences between pH- and diffusion
controlled drug releases are outlined. In a following step the characteristics of
single unit- and multiple units-dosage forms are discussed, and the predominantly
used excipients for pH- and diffusion-controlled drug release are mentioned.
Finally the influences of such special galenical designs for controlled drug
release are explained in the light of some selected examples. The exact knowledge
and consideration of these facts are extremely important in the development of
optimal drug systems, in the interpretation of results, and with respect to
interdisciplinary cooperation, e.g. between pharmaceutical technologists and
pharmacologists.
PMID- 10194943
TI - [Pharmacokinetic data for different 5-aminosalicylic acid and budesonide
preparations].
AB - Different orally and rectally applicable forms of 5-ASA and budesonide have been
developed to achieve sufficient high concentrations of the active moieties at the
site of inflammation (small and/or large bowel) and to limit the systemic action
of the drugs. This concept of drug targeting could be accomplished by both
special galenic formulations and by utilizing the pharmacokinetic properties of
the agents especially their high intestinal and hepatic presystemic elimination.
Thus, 5-ASA and budesonide represent drugs of first choice in the treatment of
Crohn's disease and ulcerative colitis. This review describes the various
pharmacokinetic and (patho)physiologic factors and their impact on drug delivery
and biological availability of the different 5-ASA and budesonide preparations.
PMID- 10194944
TI - [Clinical effects of 5-aminosalicylic acid preparations in Crohn disease].
AB - The antiinflammatory drug 5-aminosalicylic acid is available either as mesalamine
in various slightly different galenic preparations or as a prodrug with 5-ASA
bound to a carrier molecule as inert as possible, which releases 5-ASA via
bacterial degradation in the ileocolon. Data from therapeutic trials in patients
with Crohn's disease are only available for mesalamine and sulfasalazine. In
active Crohn's disease, high-dose (> 3 g per day) mesalamine only is more
effective than placebo, but inferior to systemic steroids. They may be used in
patients refusing treatment with classical steroids or not tolerating them if
this does not make a case for budesonide. The therapeutic gain of mesalamine over
placebo for the prevention recurrence in patients who have reached remission by
drug treatment is marginal. Thus, its use in this clinical situation is not
appealing. Results for the maintenance of a surgically induced remission appear
slightly better so that the use of > 3 g of mesalamine per day may be still
justified in this scenario. It is an unresolved question whether the clinical
efficacy of different galenic mesalamine prepations in maintaining postoperative
remission varies with the preoperative disease location. Present data are not
sufficient to support differential drug treatment based on this parameter.
PMID- 10194945
TI - [Clinical effect of various 5-ASA preparations in ulcerative colitis].
AB - Sulfasalazine (SASP), since 60 years standard in the treatment of ulcerative
colitis, is a double molecule where 5-aminosalicylic acid (5-ASA) and
sulfapyridine (SP) are linked together by an azobond. Bacterial splitting of SASP
within the colon allows delivery of 5-ASA for its topical action (prodrug
system). To target 5-ASA without the less tolerable SP down to the lower
intestine new prodrugs have been developed and, in addition, mesalazine is
offered which contains 5-ASA prepared as a delayed release preparation. A
clinical comparison (metaanalysis) tended towards superiority of the new prodrugs
and mesalazine over SASP for inducing remission, while SASP was more effective in
maintaining remission. Only few studies exist comparing the efficacy of the new
drugs and mesalazine. To date a slight superiority of the new prodrugs is
implied. With the exception of SASP safety profiles do not significantly differ
between the different drugs containing 5-ASA.
PMID- 10194946
TI - [Clinical effectiveness of various budesonide preparations in Crohn disease].
AB - Budesonide in the pH-dependent and time-dependent release preparation is at a
dose of 9 mg/day useful for treatment of mild to moderate active Crohn's disease.
Although the remission rates are somewhat lower as compared to systemic steroids,
the number of side effects is significantly decreased. Differences between both
preparations based on theoretical and pharmacological considerations have not yet
been proven in clinical practice. With regard to maintenance of steroid-induced
remission the data available do not justify continuous treatment. This is also
true for postoperative remission maintenance. It is not clear at the moment if
higher doses could possibly be effective for this indication. It has to be
expected, however, that side effects than will increase as well.
PMID- 10194947
TI - [Consequences of galenic differences and outcome of clinical trials with
budesonide and 5-aminosalicylic acids for therapy of Crohn disease].
AB - Budesonide in both galenic forms is suitable for the treatment of a flare of
Crohn's disease of up to moderate activity. The same holds true for 5-amino
salicylates, although they are less effective. Topical steroids delay but do not
prevent relapses. Aminosalicylates may be used in the postoperative situation for
prevention of relapse but are not significantly effective after drug-induced
remission.
PMID- 10194948
TI - [Consequences of galenic considerations and clinical results for therapy of
ulcerative colitis].
AB - Corticosteroids and 5-amino salicylic acid (5-ASA) are established therapies in
the induction of remission and in maintenance of remission in patients with
ulcerative colitis. 5-ASA exists in different delivery systems, however, clinical
studies directly comparing these preparations exist only in very limited numbers.
When analyzing placebo-controlled or comparative studies it is clearly evident
that 5-ASA is superior to placebo in both induction of remission and maintenance
therapy. In maintenance therapy prodrug compounds (sulfasalazine, SASP) seem to
be marginally better compared to 5-ASA slow release preparations. Direct
comparison of the newer 5-ASA preparations is not possible because of limited
data. Theoretical considerations based on the different principles of slow
release are also questionable since the intraluminal pH or intestinal motility
may be disturbed in IBD.
PMID- 10194949
TI - [Nicorandil: acute hemodynamic effects of 2 different oral doses of a potassium
channel opener in patients with coronary heart disease].
AB - BACKGROUND: In medical treatment of angina pectoris the 3 major groups of
antianginal agents are nitrates, beta blockers and calcium antagonists. Now a new
class of drugs is introduced in the therapy: the potassium channel openers. One
of the first potassium channel openers is nicorandil. We examined the acute
hemodynamic effects of 2 different oral nicorandil doses in patients with
coronary heart disease. PATIENTS AND METHODS: Twenty patients with angiographic
proven coronary heart disease and stable angina pectoris were treated with a dose
of 2 x 10 mg Nicorandil on day 1 and 2 x 20 mg Nicorandil on day 2, while being
hemodynamically monitored on an intensive care unit with a pulmonary artery
catheter. RESULTS: Through the hemodynamic monitoring a dose dependent,
significant reduction of systolic blood pressure was found (6%/9%), while the
heart rate increased dose dependently (6%/11%). The rate pressure product as a
marker of myocardial oxygen demand did not increase significantly. CONCLUSION:
The oral application of nicorandil causes an acute, dose dependent, significant
decrease in systolic blood pressure and induces a reflextachycardia.
PMID- 10194950
TI - [The role of problem-oriented learning programs in internal medicine; comment].
PMID- 10194951
TI - [Model trial: use and evaluation of a problem-oriented learning program in
internal medicine].
AB - BACKGROUND: Problem-based training is a new approach in medical education. It is
in particular essential that students work actively with authentic medical cases.
Modern software is appropriate for developing interactive case-based training
systems and the use in teaching environments. This method is still rarely
integrated within medical curricula. METHOD: In an educational trial with 287
students the conceptual background, feasibility and evaluation are discussed. The
learning program CASUS was used to present the case of a macroprolactinoma for
interactive training. A questionnaire with a return rate of 78% was used for
evaluation. RESULTS: 96% of the students had no problems in learning how to
handle and use the program. A major problem was to focus the contents of the
program exactly to the students' needs. The students' judgement was independent
of the individual computer skills. 82% of the students would like to use the
program in the future. CONCLUSION: Case-based and computer-assisted learning
increases motivation and probably improves the quality in medical education.
Controlled trials have to be implemented in future to show the effectiveness and
the long-term output of these learning systems.
PMID- 10194952
TI - [Magnesium excretion in urine is not a marker of magnesium deficiency.
Reliability of an oral magnesium administration test].
AB - BACKGROUND: Serum magnesium analysis does not reflect body content of magnesium.
So substitution is based on empirical maneuvers. PATIENTS AND METHOD: In a study
on 44 patients urinary magnesium excretion was analyzed before and after oral
magnesium substitution (40 mval). The provable hypothesis was the estimation that
patients in magnesium deficiency under chronical diuretic treatment (n = 11)
would have a lower magnesium excretion than patients of the control group (n =
10). Further analysis was done with patients after orthotopic cardiac
transplantation (n = 12) and those suffering from coronary heart disease (n =
11). RESULT: After oral administration of magnesium in all 4 groups there was a
rise in blood levels, only significant in the patient group under chronic
diuretic treatment. Urinary magnesium excretion, however, showed no significant
differences. Patients after cardiac transplantation had the lowest rise in
urinary magnesium excretion. CONCLUSION: There was no clear differentiation by
means of this oral magnesium substitution test. Magnesium excretion even after
oral substitution is of no value to analyze magnesium deficiency.
PMID- 10194953
TI - [Stent restenosis: therapy concepts and possibilities for prevention].
AB - BACKGROUND: In-stent restenosis has become a significant problem for
interventional cardiologists. Due to different pathogenic causes it remains
unclear whether a uniform therapeutic regimen is appropriate. TREATMENT:
Redilatation has predominantly been used for the treatment of instent restenosis,
however, in long and diffuse restenotic stents, long-term results are reported to
be poor. Therefore, tissue-debulking techniques may have beneficial effects in
complex cases of in-stent restenosis. The therapeutic benefit of intracoronary
radiation, local drug delivery or gene transfer has not been evaluated so far.
PREVENTION: Therefore, prevention of the iatrogenic entity in-stent restenosis
has become more important.
PMID- 10194954
TI - [Antiphospholipid antibody syndrome].
AB - BACKGROUND: Antiphospholipid antibodies comprise a family of auto-antibodies
mainly characterized by the presence of the lupus anticoagulant (LA) and
anticardiolipin antibodies (ACA). CLINICAL APPEARANCE: The antiphospholipid
antibody syndrome is defined by the appearance of frequent thromboses, repeated
fetal losses and thrombocytopenia. Other clinical manifestations associated with
APA include migraine, chorea, hemolytic anemia, heart valve disease, Budd-Chiari
syndrome, perpetual pancreatitic episodes, intestinal infarctions, malignant
hypertension, livedo reticularis, pre-eclampsia, fetal growth retardation or
catastrophic antiphospholipid syndrome. LA and ACA occur in a variety of clinical
conditions (secondary antiphospholipid antibody syndrome, SAPS), including other
autoimmune disorders, infectious diseases, neoplastic disorders, in association
with the use of certain drugs or in otherwise healthy individuals (primary
antiphospholipid antibody syndrome, PAPS). TREATMENT: Patients with thrombosis
associated with APA should receive long-term anticoagulation therapy, whereas
treatment of asymptomatic patients seems to be not indicated, because only
approximately 10% of patients with APA may develop thrombotic complications. In
patients with PAPS there is no evidence that the prophylactic administration of
immunosuppressive drugs will prevent thromboembolic events.
PMID- 10194955
TI - [Duodenal ulcer with penetration into the liver. Endoscopic-biopsy diagnosis].
AB - BACKGROUND: Penetration into the liver is a rare complication of peptic ulcer.
Usually the diagnosis is made by operation or autopsy. We found only 13 reports,
in which hepatic penetration was confirmed by endoscopy and histopathological
examination of the gastroscopic biopsy. Large ulcers with a pseudotumoral mass
protruding from the ulcer bed and the presence of liver tissue in the biopsy
specimen were the main findings. CASE REPORT: We describe clinical, endoscopic
and microscopic findings in another case.
PMID- 10194956
TI - [Lyme borreliosis: current status of diagnosis and therapy].
PMID- 10194957
TI - [Excluding thrombosis].
PMID- 10194958
TI - [Rationing in medicine from the economic viewpoint].
AB - The rationing of medical care is inevitable. The economic term "rationing"
describes in a value-neutral manner that goods and services have to be withhold
if financial means are limited. A changing demographic structure of society,
rising expectations of patients as well as relatives and medical-technological
progress are the main reasons for the rising rationing pressure and these
developments can, if at all, be influenced only to a minor degree.
Rationalization, i.e. to increase efficiency is a prerequisite before any
rationing should be initiated and it often combines cost-savings with improved
patient care. Rationalisation, however, cannot render rationing unnecessary.
Rationing should take place in an explicit manner, with open discussions and
comprehensible modes of discussion. One has to ask, a) which ideas about justice
prevail in a society, b) which philosophical theory could provide a widely
accepted and coherent basis for a rationing calculus and c) how a theoretical
model can be transformed into applicable social politics and decision modes.
PMID- 10194959
TI - [Rationing in public health: what criteria, what priorities?].
AB - Rationalization in clinical care has reached its limits. Facing the need of
further reducing health care costs it is relevant to reflect which diagnostic and
therapeutic procedures are justified considering the public economic interests. A
prioritized list of covered medical care requires a consensus of physicians,
insurance companies and patients organizations on the basis of evidence-based
medicine.
PMID- 10194960
TI - ["Clinically significant" new drug interactions].
AB - The concomitant intake of drugs with the potential to cause drug interactions is
frequent. In contrast, adverse effects due to drug interactions account for only
a small fraction of all adverse effects. A reproducible evaluation of the
clinical relevance of drug interactions is lacking. We now can accurately define
the potential of a drug to cause interactions, primarily by comparative
investigations within a drug class. Whether or not the selection of the drug
based on this information is useful for the patient is unknown. Therefore,
usually it is to be recommended to abandon therapeutically reasonable drug
combinations with a risk for interactions only if equivalent therapeutic options
are available. Several actual examples on interactions with selective serotonin
re-uptake inhibitors, HMG-CoA reductase inhibitors, mibefradil, sildenafil,
protease inhibitors and with grapefruit juice are discussed.
PMID- 10194961
TI - Error-related processing during a period of extended wakefulness.
AB - The nature of error detection as manifested by the error-related negativity was
examined in both a Sternberg memory search task and a visual search task. Both
tasks were performed in conditions with consistent or varied stimulus-response
mapping and loads of three or six letters. After subjects were trained
extensively in all conditions, they performed the tasks throughout the night
without sleeping. The data suggest that the effectiveness of error detection
decreases over time because of a decrease in the quality of perceptual
processing. Error detection also suffers when performance requires more search
related resources. In both cases, the representation of the correct response is
compromised. These results indicate that error detection depends on the same
perceptual and cognitive processes that are required for correct performance.
PMID- 10194962
TI - Effects of dual task demands on the accuracy of smooth pursuit eye movements.
AB - The effect of attention allocation on smooth pursuit eye movements (SPEM) was
investigated. Eye movements were electrooculographically recorded in 27 healthy
subjects who tracked a visual target that moved horizontally with constant or
unpredictably varying velocity. In some trials, subjects performed additional
auditory discrimination tasks varying in difficulty. Pursuit error decreased when
attention was divided between both tasks. The pattern of results is incompatible
with the assumption made in previous research that attention enhancement improves
SPEM accuracy. Rather, ocular smooth pursuit appears to be executed in the
automatic mode, although intentional and selective processes must contribute.
Moreover, controlled attention directed to the tracking task interfered with
smooth pursuit. A reinterpretation of earlier studies in which visual monitoring
tasks were used to improve eye tracking is needed.
PMID- 10194963
TI - The psychobiology of strained breathing and its cardiovascular implications: a
functional system review.
AB - Strained breathing is a natural respiratory pattern, with cardiovascular
implications. It is associated with social factors, attention, expectation, and
anxiety and with defense behavior in animals. An inhibition of active behavior is
characteristic. Strained breathing is based on the functional heterogeneity of
the medullary postinspiratory neurons. In stressful circumstances, muscle tension
and laryngeal reflexes induce a strong reduction of airflow in the glottis,
resulting in a prolonged Stage I of expiration and an elevated intrathoracic
pressure. The resulting elevations of blood pressure and CO2 level further
stimulate the strained breathing pattern. The straining factor intrathoracic
pressure is an important psychophysiological parameter. Functional aspects of
strained breathing may be an elevated brain perfusion and the prevention of
hyperventilation. It induces blood pressure oscillations and respiratory sinus
arrhythmia. Frequent strained breathing may contribute to cardiovascular
pathology and sleep apnea, creating a link between functional behavior and
disease.
PMID- 10194964
TI - Gender differences in late positive components evoked by human faces.
AB - Event-related potentials (ERPs) were recorded in male and female participants in
response to 32 male and 32 female faces. Participants were instructed to simply
look carefully at each face; after ERP collection they were asked to rate each
face on a 5-point attractiveness scale. A positive correlation between average
rating and average P300 scores to opposite sex faces was observed in male (r =
.40) and in preovulatory (r = .41) and postovulatory (r = .44) female subjects.
Correlations to same sex faces were only found in postovulatory females (r =
.61). Male participants showed a much larger average P300 than did female
participants, and the P300 evoked in female participants was unexpectedly larger
to female than to male faces. Neither task relevance nor stimulus probability is
a plausible explanations for these findings because they were experimentally
controlled. These results support the emotional value hypothesis, according to
which classical P300 processes reflect an affective evaluation of the stimulus,
which in turn produces context updating.
PMID- 10194965
TI - Schizophrenic patients show facial reactions to emotional facial expressions.
AB - Facial reactions in schizophrenic patients were assessed via electromyography
(EMG) in response to pictures of facial expressions. Male patients and nonpatient
controls viewed photographs of positive and negative facial expressions while EMG
activity from the corrugator and zygomatic muscle regions was recorded. Both
schizophrenic patients and controls exhibited greater zygomatic reactivity in
response to positive pictures than in response to negative pictures and greater
corrugator reactivity in response to negative pictures than in response to
positive pictures. Schizophrenic patients exhibited greater corrugator reactivity
than did nonpatient controls. Implications for understanding emotion expression
and perception in schizophrenic patients are discussed.
PMID- 10194966
TI - Individual differences in electrodermal responsivity to predictable aversive
stimuli and substance dependence.
AB - To determine if the inability to take advantage of the predictability of an
aversive stimulus to diminish its psychological impact reflects a deficit in
inhibitory control related to the development of substance dependence, we
recorded skin conductance responses (SCRs), heart rate (HR), and anticipatory
electrodermal nonspecific fluctuations (NSFs) from 175 16-18-year-old boys when a
white noise blast was either unpredictable or temporally predictable. Compared
with boys who had moderately reduced or augmented SCRs to predictable blasts
(moderate and poor modulators, respectively), boys whose SCRs were greatly
reduced (good modulators) had fewer symptoms of alcohol and nicotine dependence
and more anticipatory NSFs. HR appeared to index an active coping response for
good and moderate modulators. The autonomic response pattern evident for good
modulators may index an inhibitory control mechanism protecting them from
developing substance dependence.
PMID- 10194967
TI - Event-related potential correlates of proactive interference in schizophrenic
patients and controls.
AB - Performance and event-related potentials (ERPs) were examined in a proactive
interference (PI) task with 15 male schizophrenic patients and 15 matched healthy
controls. Within a paired-associate task, 30 pairs of semantically unrelated
words (A-B) were presented twice, followed by cued recall, in which the paired
associate B had to be named upon cue A. Subsequently, 50% of the A-words were
paired with new words (A-C) and presented in random order together with 15 novel
pairings (D-E). Slower responses and poorer recall of C- than of E-words in the
final recall indicated PI in both groups. During acquisition, the paired
associates (C/E) evoked larger P3 and positive slow wave in controls than in
patients. During recall, cues (A/D) evoked a slow wave with predominating
anterior negativity in controls and posterior positivity in patients. The group
specific ERP pattern suggests deviant encoding and retrieval processes in
schizophrenic individuals.
PMID- 10194968
TI - A distinction between the initiation and the continuation of response
preparation.
AB - Previous findings suggest that motoric response preparation cannot be initiated
in parallel with memory scanning. In the present study, response preparation was
initiated with the aid of a precue to examine whether such preparation can be
maintained or continued while memory scanning is active. In Experiment 1, each
trial began with a colored square indicating which hand might be needed to
respond. A probe letter's memory set membership determined whether the primed
response should be made or withheld. Lateralized readiness potentials were
initiated by the square precue and continued to increase after letter
presentation, suggesting that once response preparation had been initiated it was
continued in parallel with memory scanning. Experiment 2 suggested that the
difficulty of the concurrent memory search had little effect on the continuation
of response preparation. The results support the view that motoric response
preparation consists of at least two qualitatively distinct phases--initiation
and continuation.
PMID- 10194969
TI - Poststimulus EEG spectral analysis and P300: attention, task, and probability.
AB - Event-related potentials (ERPs) were elicited with auditory stimuli, and spectral
analysis was performed on the poststimulus electroencephalographic (EEG) activity
to assess how variables that influence the P300 affect spectral parameters of the
resultant ERP. In Experiment 1, a no-stimulus condition was compared with a
single repeated tone that was either ignored or counted. In Experiment 2, an
auditory oddball paradigm was used in which the subject ignored all stimuli,
counted only the target, or counted both the target and the standard stimuli in
different conditions. In Experiment 3, stimulus probability was manipulated in
separate conditions (.20, .50, .80), with the subject required to count the
target stimulus. Delta and theta band spectral power increased whenever P300
amplitude increased. However, as the attentional requirements increased across
tasks, alpha-1 and alpha-2 power and mean frequency increased. The findings
indicate that auditory stimulus processing modulates the EEG more than just by
adding ERP components to the epoch.
PMID- 10194970
TI - How many nights are enough? The short-term stability of sleep parameters in
elderly insomniacs and normal sleepers.
AB - Temporal stability is an important fundamental quality when measuring sleep
parameters, yet it has been infrequently assessed. Generalizability theory was
used to estimate the short-term temporal stability of five variables commonly
used to characterize insomnia: sleep onset latency, total sleep time, wake after
sleep onset, time in bed, and sleep efficiency. Estimates were calculated for 32
elderly primary insomniacs and 32 elderly normal sleepers, both in the lab and at
home, using both sleep logs and polysomnography (PSG). A week of recording using
either PSG or sleep logs was typically sufficient to achieve adequate stability
(defined as G coefficient of at least 0.80) with some notable exceptions: (a)
when using log-derived measures with insomniacs, a 3-week average was necessary
for wake after sleep onset and (b) more than a 2-week average was necessary for
sleep onset latency. Because of the substantial commitment involved in the
physiological recording of sleep, alternative forms of aggregation are considered
with the intent of improving temporal stability.
PMID- 10194971
TI - Dominance, gender, and cardiovascular reactivity during social interaction.
AB - Associations between trait dominance and cardiovascular reactivity were examined
in previously unacquainted healthy men and women. Subjects participated in three
mixed-gender dyadic interactions with the same partner while their cardiovascular
responses were assessed. Among men, but not women, trait dominance was positively
and significantly associated with systolic blood pressure reactivity. For men and
women, diastolic blood pressure reactivity was positively and significantly
associated with trait dominance while participants prepared to interact and with
partner's trait dominance while they interacted. All effects held after
controlling for trait hostility. Dominance merits attention as a correlate of
cardiovascular reactivity, a finding that parallels emerging patterns in the
cardiovascular disease literature. Gender and gender-related social factors as
potential moderators of this relationship are discussed.
PMID- 10194972
TI - Measuring facial expressions by computer image analysis.
AB - Facial expressions provide an important behavioral measure for the study of
emotion, cognitive processes, and social interaction. The Facial Action Coding
System (Ekman & Friesen, 1978) is an objective method for quantifying facial
movement in terms of component actions. We applied computer image analysis to the
problem of automatically detecting facial actions in sequences of images. Three
approaches were compared: holistic spatial analysis, explicit measurement of
features such as wrinkles, and estimation of motion flow fields. The three
methods were combined in a hybrid system that classified six upper facial actions
with 91% accuracy. The hybrid system outperformed human nonexperts on this task
and performed as well as highly trained experts. An automated system would make
facial expression measurement more widely accessible as a research tool in
behavioral science and investigations of the neural substrates of emotion.
PMID- 10194973
TI - An event-related brain potential study of visual selective attention to
conjunctions of color and shape.
AB - What cognitive processes underlie event-related brain potential (ERP) effects
related to visual multidimensional selective attention and how are these
processes organized? We recorded ERPs when participants attended to one
conjunction of color, global shape and local shape and ignored other conjunctions
of these attributes in three discriminability conditions. Attending to color and
shape produced three ERP effects: frontal selection positivity (FSP), central
negativity (N2b), and posterior selection negativity (SN). The results suggested
that the processes underlying SN and N2b perform independent within-dimension
selections, whereas the process underlying the FSP performs hierarchical between
dimension selections. At posterior electrodes, manipulation of discriminability
changed the ERPs to the relevant but not to the irrelevant stimuli, suggesting
that the SN does not concern the selection process itself but rather a cognitive
process initiated after selection is finished. Other findings suggested that
selection of multiple visual attributes occurs in parallel.
PMID- 10194974
TI - So nicotine is addictive ... so what?
PMID- 10194975
TI - Cause of ARDS.
PMID- 10194976
TI - Pain, death, and doctors.
PMID- 10194977
TI - Health care stocks make slow recovery.
PMID- 10194978
TI - Lessons for physicians. Why are hospitals losing money?
PMID- 10194979
TI - Loss prevention case of the month. Inattentive to essential details.
PMID- 10194980
TI - Divalproex sodium--review of prophylactic migraine efficacy, safety and dosage,
with recommendations.
PMID- 10194981
TI - Limb ischemia secondary to open pelvic fractures: a rare combination.
PMID- 10194982
TI - Recurrent skin lesions in a middle-age woman.
PMID- 10194983
TI - The Tennessee HIV Pregnancy Screening Act of 1997.
PMID- 10194984
TI - Costing model for neonatal screening and diagnosis of haemoglobinopathies.
AB - AIM: To compare the costs and cost effectiveness of universal and targeted
screening for the haemoglobinopathies; to compare the cost of two laboratory
methods; and to estimate the cost effectiveness of programmes at different levels
of prevalence and mix of haemoglobinopathy traits. METHODS: A retrospective
review of laboratory and follow up records to establish workload and costs, and
estimation of costs in a range of circumstances was made in a haematology
department and sickle cell and thalassaemia centre, providing antenatal and
neonatal screening programmes in Inner London. The costs for 47,948 babies,
screened during 1994, of whom 25 had clinically significant haemoglobinopathies
and 704 had haemoglobinopathy traits, were retrospectively assessed. RESULTS: The
average cost per baby tested (isoelectric focusing and high power liquid
chromatography) was 3.51 Pounds /3.83 Pounds respectively; the cost per case of
sickle cell disease identified (IEF/HPLC) was 6738 Pounds /7355 Pounds; the cost
per trait identified (IEF/HPLC) was 234 Pounds /255 Pounds; the cost per extra
case of SCD and trait identified by universal programme varied. CONCLUSIONS: IEF
and HPLC are very similar in terms of average cost per test. At 16 traits/1000
and 0.5 SCD/1000 there was no significant identification cost difference between
universal and targeted programmes. Below this prevalence, a targeted programme is
cheaper but likely to miss cases of SCD. If targeted programmes were 90-99%
effective, universal programmes would cease to be good value except at very high
prevalence. Greater use of prenatal diagnosis, resulting in termination, and
therefore fewer affected births, reduces the cost effectiveness of universal
screening. Screening services should aim to cover a screened population which
will generate a workload over 25,000 births a year, and preferably over 40,000.
PMID- 10194985
TI - Compiling a national register of babies born with anophthalmia/microphthalmia in
England 1988-94.
AB - AIM: To describe the prevalence of anophthalmia/microphthalmia in babies born in
England 1988-94, as well as their overall survival, and the incidence of
associated eye and non-eye malformations; to determine the usefulness of
different sources of medical and health service information for establishing a
retrospective register of anophthalmia/microphthalmia. METHODS: Multiple sources
for initial (retrospective) case ascertainment were surveyed, followed by
questionnaires to clinicians to establish severity, associated malformations, and
aetiology for England, 1988-94. The population surveyed was all births in England
for this time period (4,570,350 births). Cases included live births, stillbirths,
or terminations after prenatal diagnosis of congenital anomaly, with
anophthalmia/microphthalmia, with or without other malformations and syndromes.
Trisomy 13 was subsequently excluded. RESULTS: The proportion of cases notified
by any one information source was not more than 26% (Office for National
Statistics Register 22%, paediatricians 26%, district sources 25%). Sixty nine
per cent of cases (51% of severe cases) were notified by only one source. A total
of 449 cases were reported, prevalence 1.0 per 10,000 births. The prevalence was
stable over time, although the proportion notified by clinicians rose in more
recent years. Thirty four per cent of affected babies had mild microphthalmia. Of
those with severe anophthalmia/microphthalmia, 51% were bilateral, other eye
malformations were present in 72%, non-eye malformations in 65%, and a "known
aetiology" was attributed in 22%. Three quarters of those severely affected
survived infancy. CONCLUSIONS: Despite high response rates from the sources of
information contacted, the lack of duplication between sources indicates the
difficulties of retrospective ascertainment and the need for multiple sources
when establishing a register. Anophthalmos/microphthalmos is usually associated
with other malformations. Most cases are of unknown aetiology.
PMID- 10194986
TI - Long-term neurological dysfunction and neonatal hypoglycaemia after diabetic
pregnancy.
AB - AIM: To determine if children born to mothers with diabetes mellitus during
pregnancy, who subsequently developed neonatal hypoglycaemia, experienced long
term neurological dysfunction. METHODS: Thirteen children with, and 15 without,
neonatal hypoglycaemia (blood glucose < 1.5 mmol/l) were randomly selected from a
larger cohort and investigated at the age of 8 years. They were also compared
with 28 age matched healthy controls. RESULTS: Children with neonatal
hypoglycaemia had significantly more difficulties in a validated screening test
for minimal brain dysfunction than controls and were also more often reported to
be hyperactive, impulsive, and easily distracted. On psychological assessment,
they had a lower total development score than normoglycaemic children born to
diabetic mothers, and control children. CONCLUSIONS: Neonatal hypoglycaemia in
diabetic pregnancy was associated with long-term neurological dysfunction related
to minimal brain dysfunction/deficits in attention, motor control, and
perception.
PMID- 10194987
TI - Circulatory changes induced by isovolumic increase in red cell mass in fetal
lambs.
AB - AIM: To verify whether extra uterine changes in total peripheral vascular
resistance and cardiac output, caused by raised haematocrit, occur in fetal life
and if they can be documented using conventional ultrasound techniques. METHODS:
An exchange transfusion with packed red cells was performed on five fetal lambs
at 140 days of gestation (weight 3.44, SD 0.48 kg); three others were used as
controls. The haematocrit was raised from 44 +/- 3 to 64 (SD2)%. RESULTS: Body
temperature, blood gas, and pH remained within normal limits. Blood viscosity
increased from 5.3 (0.3) to 9.6 (1.6) cps. Combined cardiac output fell to 30% of
its initial value. The pulsatility index (PI) remained unchanged in the umbilical
artery (0.66, SD 0.1) and descending aorta (1.3, SD 0.3). A significant positive
correlation was found between haematocrit and PI only in the carotid artery (r =
0.67, p < 0.01). CONCLUSION: In the fetus, as in adults, an increase in blood
viscosity is associated with a fall in cardiac output. However, the low
resistance and the relative inertia of the placental vascular bed blunt the
velocimetric changes that could be induced in the lower body vascular system by
an increase in resistance. Such changes were observed only in the carotid artery.
These results could be of interest in the Doppler monitoring of human fetuses at
risk of an abnormal increase in their haematocrit.
PMID- 10194988
TI - Incidence of cranial ultrasound abnormalities in apparently well neonates on a
postnatal ward: correlation with antenatal and perinatal factors and neurological
status.
AB - AIM: To evaluate cranial ultrasonography and neurological examination in a cohort
of infants regarded as normal; and to determine the prevalence of ultrasound
abnormalities and any potential association with antenatal or perinatal factors
or deviant neurological signs. METHODS: Cranial ultrasound findings and
neurological status were evaluated in 177 newborns (gestational age 36.3 to 42
weeks), admitted to a postnatal ward directly after birth and regarded as normal
by obstetric and paediatric staff. The age of the infants at the time of
examination ranged between 6 and 48 hours. Ultrasound abnormalities were present
in 35 of the 177 infants studied (20%). Ischaemic lesions, such as
periventricular and thalamic densities were the most common finding (8%),
followed by haemorrhagic lesions (6%). The possible sequelae of antenatal
haemorrhages, such as focal ventricular dilatation or choroid cysts, were present
in 6%. Abnormal ultrasound findings were not significantly associated with signs
of perinatal distress, such as cardiotocographic abnormalities or passage of
meconium. Abnormal ultrasound findings tended to be associated with antenatal
problems, although this did not reach significance. Ultrasound abnormalities were
strongly associated with deviant patterns on the neurological examination.
CONCLUSIONS: These results suggest that ultrasound abnormalities are more common
than has been reported up to now. Lesions that could be ischaemic, such as flare
densities, are seen even in the absence of any antenatal or perinatal risk
factor.
PMID- 10194989
TI - Predictive value of plasma and cerebrospinal fluid tumour necrosis factor-alpha
and interleukin-1 beta concentrations on outcome of full term infants with
hypoxic-ischaemic encephalopathy.
AB - AIM: To determine the predictive value of plasma and cerebrospinal fluid (CSF)
tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta)
concentrations on the outcome of hypoxic-ischaemic encephalopathy (HIE) in full
term infants. METHODS: Thirty term infants with HIE were included in the study.
HIE was classified according to the criteria of Sarnat and Sarnat. Blood and CSF
were obtained within the first 24 hours of life and stored until assay. Five
infants died soon after hypoxic insult. Neurological examinations and Denver
Developmental Screening Test (DDST) were performed at 12 months in the survivors.
RESULTS: At the age of 12 months neurological examination and DDST showed that 11
infants were normal; 14 had abnormal neurological findings and/or an abnormal
DDST result. Eleven normal infants were classified as group 1 and 19 infants (14
with abnormal neurological findings and/or an abnormal DDST and five who died) as
group 2. CSF IL-1 beta and TNF-alpha concentrations in group 2 were significantly
higher than those in group 1. Plasma IL-1 beta and TNF-alpha concentrations were
not significantly different between the two groups. IL-1 beta, but not TNF-alpha
concentrations, in group 2 were even higher than those in group 1, although non
survivors were excluded from group 2. When the patients were evaluated according
to the stages of Sarnat, the difference in the three groups was again
significant. Patients whose CSF samples were taken within 6 hours of the hypoxic
insult had higher IL-1 beta and TNF-alpha concentrations than the patients whose
samples were taken after 6 hours. CONCLUSIONS: Both cytokines probably contribute
to the damage sustained by the central nervous system after hypoxic insult. IL-1
beta seems to be a better predictor of HIE than TNF-alpha.
PMID- 10194990
TI - Randomised controlled trial of low dose fentanyl infusion in preterm infants with
hyaline membrane disease.
AB - AIM: To evaluate the effects of low dose fentanyl infusion analgesia on
behavioural and neuroendocrine stress response and short term outcome in
premature infants ventilated for hyaline membrane disease. METHODS: Twenty seven
ventilated preterm infants were randomly assigned to receive a mean fentanyl
infusion of 1.1 (0.08 SE) micrograms/kg/h for 75 (5) hours, and 28 untreated
infants were considered a control group. A behavioural sedation score was used to
assess the infants' behaviour. Urinary metanephrine and the
normetanephrine:creatinine molar ratio were determined at 0, 24, 48 and 72 hours.
Outcome data and ventilatory indexes were recorded for each infant. RESULTS: The
fentanyl group showed significantly lower behavioural stress scores and O2
desaturations than controls and lower urinary concentrations of metanephrine and
normetanephrine at 24, 48, 72 hours. The two groups showed no significant
difference in ventilatory variables or short term outcome. CONCLUSIONS: A short
course of low dose fentanyl infusion reduces behavioural sedation scores, O2
desaturations and neuroendocrine stress response in preterm ventilated infants.
PMID- 10194991
TI - Caeruloplasmin isoforms in Wilson's disease in neonates.
AB - AIM: To investigate the neonatal diagnosis of Wilson's disease from
caeruloplasmin isoforms in cord blood. METHODS: Serum caeruloplasmin isoforms
were measured in 5-10 ml cord blood from 10 fresh umbilical cords using sodium
dodecyl polyacrylamide gel electrophoresis (SDS PAGE) and western blotting and
analysed by densitometry. Total caeruloplasmin concentrations were determined by
nephelometry and caeruloplasmin oxidase by p-nitrophenyldiamine. RESULTS:
Although total caeruloplasmin concentrations are reduced in neonates, the plasma
isoform was significantly reduced or absent in patients with Wilson's disease.
Sera from healthy neonates and from those with Wilson's disease had reduced
biliary isoforms. CONCLUSION: Identification of caeruloplasmin isoforms may be a
marker for Wilson's disease in neonates.
PMID- 10194993
TI - Immunogenicity of hepatitis B vaccine in preterm infants.
AB - AIM: To assess the immunogenicity of hepatitis B vaccine in preterm and term
infants, given in a sequence of three doses beginning soon after birth. METHOD:
The immunogenicity of hepatitis B vaccine was assessed in 176 preterm infants (<
35 weeks of gestation), immunised soon after birth, and compared with that in 46
term infants. Titres of hepatitis B antibodies were determined one to two months
after the third vaccine. The significance of the differences between the term and
preterm groups was determined using Student's t test. RESULTS: A similar
proportion of infants in both preterm and term groups attained protective titres
of hepatitis B antibodies (88.7% vs 93.4%, respectively; p = NS). However, the
term infants had a higher geometric mean titre of antibodies after the third
vaccine than did the preterm infants (701.2 (745.0) vs 469.1 (486.2) mU/ml,
respectively; p < 0.03). CONCLUSION: Hepatitis B vaccine is effective in most
preterm infants when given soon after birth. It may be advisable to determine the
immune response at 12-24 months of age to booster the non-responders.
PMID- 10194992
TI - Placental antibody transfer: influence of maternal HIV infection and placental
malaria.
AB - AIM: To determine the influence of placental malaria, maternal HIV infection, and
maternal hypergammaglobulinaemia on transplacental IgG antibody transfer.
METHODS: One hundred and eighty materno-neonatal pairs from a Malawian population
were assessed. Cord and maternal serum samples were tested for total serum IgG
antibody titres using nephelometry, and for specific IgG antibody titres to
Streptococcus pneumoniae, measles, and tetanus toxoid antibodies using an enzyme
linked immunosorbent assay (ELISA). RESULTS: Multiple regression analyses showed
that placental malaria was associated with a decrease in placental IgG antibody
transfer to S pneumoniae and measles to 82% and 81%, respectively. Maternal HIV
infection was associated with a reduction in IgG antibody transfer to S
pneumoniae to 79%; raised maternal total serum IgG titres were correlated with S
pneumoniae and measles IgG antibody transfer reduction to 86% and 87%,
respectively. No effect was seen with tetanus toxoid antibody transfer.
CONCLUSION: The combined influence of placental malaria, maternal HIV infection,
and maternal hypergammaglobulinaemia seems to be linked to the low transplacental
antibody transfer observed in the Malawian population.
PMID- 10194994
TI - Randomised controlled trial of paracetamol for heel prick pain in neonates.
AB - AIM: To evaluate the effectiveness of paracetamol in decreasing the pain from
heel prick. METHODS: A prospective randomised double blind placebo controlled
trial was conducted of 75 term neonates undergoing heel prick. Sixty to 90
minutes before the procedure neonates received paracetamol orally in a dose of 20
mg/kg (group 1) or an equal volume of placebo (group 2). Heel prick was performed
in a standardised manner. Pain assessments were made using per cent facial action
(brow bulge, eye squeeze, and nasolabial fold (range 0-300%) and per cent of time
spent crying (range 0-100%). RESULTS: Thirty eight neonates were enrolled in
group 1 and 37 neonates in group 2. There were no significant differences in the
demographic characteristics between groups. Mean gestational age was 39 (SD 1.4)
vs 39.4 (SD 1.2) weeks, p = 0.86, mean birthweight 3.45 (SD 0.45) vs 3.44 (SD
0.42) kg; p = 0.31 for groups 1 and 2, respectively. Facial action pain scores
did not differ between groups (143.5 (SD 54.2)% vs 131.1 (SD 59.6)%; p = 0.38).
Cry scores also did not differ (29.4 (SD 19.9)% vs 26.8 (SD 20.2)%; p = 0.60). No
adverse effects were observed. CONCLUSION: Paracetamol is ineffective for
decreasing the pain from heel prick in term neonates.
PMID- 10194995
TI - Influence of erythromycin on establishment of feeding in preterm infants:
observations from a randomised controlled trial.
AB - AIM: To determine the effect of erythromycin on the establishment of enteral
feeding in ventilated infants < 31 weeks gestation. METHODS: Erythromycin was
randomly allocated as an antimicrobial treatment for the first 7 days of life in
76 infants: 35 received erythromycin and 41 acted as controls. Feed toleration,
time taken to establish full enteral feeding, vomiting, prescription of glycerine
suppositories and occurrence of necrotising enterocolitis were recorded. RESULTS:
There were no significant differences between the groups for any of the outcomes.
The infants treated with erythromycin reached full feeding at a median (quartile)
age of 8 (5-12) days compared with 9 (6-14) days for controls. CONCLUSIONS:
Intravenous erythromycin in antimicrobial doses is unlikely to benefit the
introduction of feeding in preterm infants.
PMID- 10194996
TI - Trisomy 21 associated transient neonatal myeloproliferation in the absence of
Down's syndrome.
AB - Although usually associated with Down's syndrome, transient neonatal
myeloproliferation (TMD) can occur in the absence of a constitutional trisomy 21.
This report describes two such cases, both of whom had a trisomy 21 restricted to
clonal cells. Unlike in previous such reported cases, spontaneous morphological,
cytogenetic, and molecular remission in both cases was followed by re-emergence,
in one case, of an evolved clone with a more malignant phenotype which required
pharmacological intervention. Awareness that trisomy 21 bearing leukaemia in the
neonatal period can be transient even in the absence of Down's syndrome is
important to prevent unnecessary treatment. Equally, such cases require
indefinite follow up as a proportion may have a recurrence which may require
treatment.
PMID- 10194997
TI - Effect of vitamin K1 on glucose-6-phosphate dehydrogenase deficient neonatal
erythrocytes in vitro.
AB - AIM: To determine whether vitamin K1, which is routinely administered to
neonates, could act as an exogenous oxidising agent and be partly responsible for
haemolysis in glucose-6-phosphat-dehydrogenase (G-6-PD). METHODS: G-6-PD
deficient (n = 7) and control (n = 10) umbilical cord blood red blood cells were
incubated in vitro with a vitamin K1 preparation (Konakion). Two concentrations
of Vitamin K1 were used, both higher than that of expected serum concentrations,
following routine injection of 1 mg vitamin K1. Concentrations of reduced
glutathione (GSH) and methaemoglobin, indicators of oxidative red blood cell
damage, were determined before and after incubation, and the mean percentage
change from baseline calculated. RESULTS: Values (mean (SD)) for GSH, at
baseline, and after incubation with vitamin K1 at concentrations of 44 and 444
microM, respectively, and percentage change from baseline (mean (SD)) were 1.97 +
0.31 mumol/g haemoglobin, 1.89 +/- 0.44 mumol/g (-4.3 +/- 13.1%), and 1.69 +/-
0.41 mumol/g (-14.5 +/- 9.3%) for the G-6-PD deficient red blood cells, and 2.27
+/- 0.31 mumol/g haemoglobin, 2.09 +/- 0.56 mumol/g (-7.2 +/- 23.2%), and 2.12 +/
0.38 mumol/g (-6.0 + 14.1%) for the control cells. For methaemoglobin
(percentage of total haemoglobin), the corresponding values were 2.01 +/- 0.53%,
1.93 +/- 0.37% (-0.6 +/- 17.4%) and 2.06 +/- 0.43% (5.7 +/- 14.2%) for the G-6-PD
deficient red blood cells, and 1.56 +/- 0.74%, 1.70 +/- 0.78% (12.7 +/- 21.9%),
and 1.78 +/- 0.71% (20.6 +/- 26.8%) for the control red blood cells. None of the
corresponding percentage changes from baseline was significantly different when G
6-PD deficient and control red blood cells were compared. CONCLUSIONS: These
findings suggest that G-6-PD deficient red blood cells are not at increased risk
of oxidative damage from vitamin K1.
PMID- 10194998
TI - "Dewatering" of the lungs at birth.
PMID- 10195000
TI - Maimonides (1135-1204) and his philosophy of medicine.
PMID- 10194999
TI - Confined placental mosaicism and intrauterine fetal growth.
PMID- 10195001
TI - Justification in radiation protection.
PMID- 10195002
TI - Image guided breast biopsy--technical advances.
PMID- 10195003
TI - A comparison of a non-ionic dimer, iodixanol with a non-ionic monomer, iohexol in
low dose intravenous urography.
AB - A prospective, double-blind study of 392 patients randomized into four groups was
performed to establish whether diagnostic intravenous urograms could be obtained
with a lower dose of iodine when using the dimeric, non-ionic contrast medium
iodixanol compared with the monomeric, non-ionic iohexol. Patients received
iodixanol or iohexol containing either 9 or 12 g of iodine (gI). The primary
parameter was the diagnostic quality of the 6 min film, assessed in a blinded
fashion, by consensus, by four radiologists. Iodixanol at both doses was
diagnostic in over 90% of cases. Iohexol was only diagnostic in 74% (9 gI) and
81.8% (12 gI). Pairwise comparisons revealed that iodixanol 9 gI was
significantly better than both iohexol 9 gI (p = 0.0005) and 12 gI (p = 0.014).
No significant difference was present for different doses within the same
contrast medium group. Iodixanol resulted in poorer bladder distension than
iohexol. Iodixanol caused significantly less discomfort than iohexol.
PMID- 10195005
TI - CT dimensions of the normal pericardium.
AB - Previous studies have suggested that the upper limit of the thinnest portion of
the pericardium is 3-4 mm using 10 mm CT slices. However, these studies suffered
from small sample sizes, long data acquisition times and unconventional viewing
parameters. We have measured the width of the thinnest portion of the normal
pericardium using 10 mm (100 patients) and 1 mm (100 patients) high resolution CT
(HRCT) slices with modern CT equipment and fixed mediastinal window settings
(400/20). The pericardium was identified in all patients and was best seen
anterior to the heart. The pericardium is exceptionally well seen using 1 mm HRCT
slices and this may be the optimal technique for visualization of the
pericardium. The upper limit of the thinnest portion of the normal pericardium
(mean value + 2 SD) was 1.2 mm (10 mm CT slices) and 0.7 mm (1 mm HRCT slices).
These values are substantially lower than those previously reported and in line
with anatomical findings.
PMID- 10195004
TI - Comparison between the efficacy of dimeric and monomeric non-ionic contrast media
(iodixanol vs iopromide) in urography in patients with mild to moderate renal
insufficiency.
AB - Non-ionic dimers induce less diuresis than non-ionic monomers, resulting in
increased opacification of the urinary tract in intravenous (i.v.) urography.
This double blind, comparative, randomized, parallel trial compared the efficacy
of iodixanol (non-ionic dimer) and iopromide (non-ionic monomer) in 100 patients
with mild to moderate renal insufficiency (serum creatinine of 135 to 265 mumol l
1) who underwent i.v. urography. A total dose of 600 mgI kg-1 bw of iodixanol
(320 mgI ml-1) or iopromide (300 mgI ml-1) was injected. Radiographs were blindly
evaluated by three radiologists who analysed different parameters (renal border
visualization, nephrogram density, calyceal filling and density, papillary blush
detection, delineation of collecting ducts, renal pelvis opacification,
visualization of ureters, bladder density, bladder distention). Densitometric
evaluation on the renal pelvis and bladder was also performed. Iodixanol showed
better filling and density of the calyces (p = 0.004), more frequent detection of
papillary blush (p = 0.003) and better opacification of the renal pelvis (p =
0.006). No significant differences between the two contrast media were found in
regard to other parameters. In conclusion, the results confirmed theoretical
expectations. The non-ionic dimer iodixanol is to be preferred to a non-ionic
monomer such as iopromide in i.v. urography on patients with impaired renal
function.
PMID- 10195006
TI - Magnetic resonance imaging of soft tissue expanders used in the management of
musculoskeletal sarcomas.
AB - A soft tissue expander is surgically inserted into the body to displace
radiosensitive organs from the treatment field in a small number of patients
receiving radiotherapy for musculoskeletal sarcoma. MRI is routinely used to
monitor the response to the radiotherapy, local recurrence and complications of
treatment. This study retrospectively reviews MRI of soft tissue expanders in
seven patients with musculoskeletal sarcomas; six arising in the pelvis and one
in the retroperitoneum. In the absence of an appropriate clinical history, the
soft tissue expander may be mistaken for a pathological fluid collection such as
abscess, post-operative seroma or even recurrent tumour. MRI of the soft tissue
expanders and potential errors in image interpretation are illustrated.
PMID- 10195007
TI - An in vitro study comparing two different film-screen combinations in the
detection of impacted fish bones.
AB - Dried fish bones from eight species of Malaysian fish were placed in an animal
cadaver at four sites (tonsil, valleculae, larynx and oesophagus) and
radiographed using a double and a single film-screen combination. The use of the
single film-screen combination resulted in visibility of all fish bones placed in
the larynx, two of which were not visible on the double film-screen combination.
There was a 50% increase of the visibility of the fish bones in the oesophagus
using the single film-screen combination. The difference in dose and cost between
the two different film-screen combinations was not significant.
PMID- 10195008
TI - Diagnosis of osteoporosis by planar bone densitometry: can body size be
disregarded?
AB - Bone densitometry using dual energy X-ray absorptiometry (DXA) is frequently used
to diagnose osteoporosis and to identify patients at risk of later fractures. The
parameters of interest are bone mineral content (BMC) and bone mineral areal
density (BMD). Bone densitometry results have a large overlap between normals and
patient with fractures. This would suggest that other factors are important for
the development of fractures or that bone densitometry is not used optimally. It
is generally believed that the conversion of BMC to BMD by division of the former
by the projected bone area is a good normalization procedure. Other normalization
procedures have been attempted in the past with little success. We hypothesized
that this might be due to a blurring effect of time since menopause, and that
body size could be demonstrated to have an effect on measured BMC and BMD, if
this time effect could be eliminated. The results of this study, comprising 1625
early post-menopausal women studied at virtually the same time since menopause,
confirm that this is the case. Body surface area was the parameter among
conventional body size variables showing the highest correlation with BMC and
BMD. It was clearly shown that low values of BMD were seen more often in the
lowest than in the highest body surface area quartile. The difference between
quartiles was statistically significant. Simple division of BMC by actual body
surface area or division of BMD by the square root of body surface removed the
uneven distribution between the body surface area quartiles for lumbar spine and
femoral neck measurements, and reduced it at peripheral measuring sites. It is
suggested that BMC and BMD of the lumbar spine and the femoral neck should be
normalized as described to avoid overdiagnosis of osteoporosis in persons of
petite body stature and underdiagnosis in tall ones.
PMID- 10195009
TI - The diagnostic X-ray protection characteristics of Ytong, an aerated concrete
based building material.
AB - Ytong is a widely used building material. The X-ray attenuation properties of
Ytong for broad beam geometry conditions and for tube potentials in the 50-140
kVp range are investigated. Comparisons with published data for concrete and
other building materials are made. The results suggest that Ytong is not suitable
for primary X-ray shielding in common diagnostic installations. However, walls of
Ytong, typically 15-20 cm thick, may offer adequate protection in dental and
mammography installations, as well as in low workload diagnostic installations as
a secondary barrier.
PMID- 10195010
TI - Optimizing optical density of a Kodak mammography film-screen combination with
standard-cycle processing.
AB - The optimization of optical density in film-screen mammography is crucial in
attaining good image quality. While a target range for film optical density of
1.4-1.8 has been recommended for centres participating in the National Health
Service Breast Screening Programme (NHSBSP), past investigations have shown that
combinations of mammography film and screen and processor conditions can have
various optimum densities, some of which are outside this recommended range. The
optimum optical density of the film/screen/processor conditions combination used
at our institution (the Kodak MIN-RM/MIN-R combination designed for standard
cycle processing) was evaluated using a breast detail phantom study. It was found
that the optimum optical density was 1.25 OD. We recommend that an individual
institution determines the optimum optical density for the film-screen
combination it uses and the processing conditions specific to it.
PMID- 10195011
TI - Radiation exposure to medical staff in interventional and cardiac radiology.
AB - The aim of this work has been to determine typical occupational dose levels in
interventional radiology and cardiology installations and to relate doses to
patient and occupational dosimetry through the dose-area product. An experimental
correlation between environmental dosimetric records and dose-area products in
the centres studied was established. The study covered a sample of 83 procedures
performed by 10 specialists in six laboratories. The radiologists and
cardiologists monitored wore nine thermoluminescent chips next to eyes, forehead,
neck, hands, left shoulder, left forearm and left arm during each single
procedure. In addition, direct reading electronic devices for environmental
dosimetry were placed in the C-arm of the X-ray system, to estimate roughly the
occupational radiation risk level. Typical shoulder doses derived from electronic
dosimetry range between 300 and 500 muSv per procedure, assuming no lead
protective screens were used. Using these values and patient dose-area data from
two laboratories, averaged ratios of 84 and 120 muSv per 1000 cGy cm2 are
obtained for cardiology procedures. Finally, occupational dose reductions of
approximately 20% when using highly filtered X-ray beams with automatic tube
potential (kV) reduction (available in some facilities), and by a factor of about
three when using ceiling mounted screens, have been found.
PMID- 10195012
TI - Dose-area product readings for fluoroscopic and plain film examinations,
including an analysis of the source of variation for barium enema examinations.
AB - This paper contains the results of an investigation undertaken between 1994 and
1996 using dose-area product (DAP) meters for monitoring radiation doses from six
types of simple examinations and seven types of complex examinations. Mean
hospital DAP levels have been compared with National Reference Levels (NRL), with
most departments producing levels lower than NRLs. DAP readings have allowed the
proposal of provisional Reference Levels (RL) to be set for simple and complex
examinations. The results were also compared with recently published data from
the National Radiological Protection Board (NRPB), highlighting those hospitals
which need to make changes in radiographic technique. The study of DAP reference
doses also confirms that dose levels for complex investigations are clearly
related to technique, in terms of screening time and number of films. Although
the use of increased screening tube kilovoltage may be relevant, the overall
effect is small. The results suggest that there is still a need to optimize the
protocols for these examinations. The use of digital equipment has been shown to
have a complex effect on dose, particularly in the case of investigations
involving both films and fluoroscopy.
PMID- 10195013
TI - Determining the conditions for measurement of spatial-peak temporal-averaged
intensity in scanned ultrasound beams.
AB - This paper describes a new three stage approach which simplifies the process of
measurement of spatial-peak temporal-averaged intensity for scanned ultrasound
beams. Firstly, the conditions delivering the maximum total acoustic power are
determined. Secondly, out-of-plane beam-widths are measured which, together with
knowledge of the in-plane scan widths, are used to locate the depth at which the
scanned area is at a minimum. Finally, the spatial-peak temporal-average
intensity is measured using the conditions and depth identified in the first two
stages. Experimental results justify the use of this new procedure.
PMID- 10195014
TI - Aorto-oesophageal fistula presenting as a submucosal oesophageal haematoma.
AB - The CT findings in a fatal case of aorto-oesophageal fistula secondary to an
atheromatous plaque in the thoracic aorta are described. These features are
correlated with findings on endoscopy and barium studies.
PMID- 10195015
TI - Radiological findings in myxoid liposarcoma of the anterior mediastinum.
AB - CT and MR findings of a rare myxoid liposarcoma involving the anterior
mediastinum are reported. The mass was a low density lesion with calcific
septations and some peripheral frond-like enhancement on CT. MRI showed
heterogeneous intermediate to high signal intensity on T1 weighted images and
high signal intensity on T2 weighted images. The signal of the mass was not
suppressed on fat suppressed images.
PMID- 10195016
TI - Renal cell carcinoma with a fatty component mimicking angiomyolipoma on CT.
AB - A very unusual CT appearance of renal cel carcinoma is presented, in which the
fatty density mimicked a benign angiomyolipoma.
PMID- 10195017
TI - Synovial presentation of non-Hodgkin's lymphoma.
AB - The MRI appearances of synovial involvement from non-Hodgkin's lymphoma are
described in a 61-year-old man. These appearances have not previously been
described and the differential diagnosis is discussed.
PMID- 10195018
TI - Colon ischaemia secondary to barolith obstruction.
AB - A case is described of an elderly woman who developed an obstructing barolith in
the sigmoid colon following a barium enema. Colonic ischaemia developed in the
proximal colon. Predispositions and prevention of baroliths are discussed.
PMID- 10195019
TI - Imaging of pancreatic trauma.
AB - This pictorial review discusses the imaging findings in acute pancreatic injury
and its delayed complications. These findings are related to key decisions in
surgical management. Emphasis is placed on the difficulty of acute diagnosis
using CT and the pivotal role of endoscopic retrograde pancreatography (ERP) in
the definition of ductal anatomy with delayed diagnosis.
PMID- 10195020
TI - A sinus problem?
PMID- 10195022
TI - Estimation of effective dose in diagnostic radiology from entrance surface dose
and dose-area product measurements.
PMID- 10195021
TI - Fan beam dual X-ray absorptiometry: an important advance in bone densitometry.
PMID- 10195023
TI - Contact tracing--where do we go from here?
PMID- 10195024
TI - Sexually transmitted infection in the elderly.
PMID- 10195025
TI - Pathogenesis and treatment of HTLV-I associated myelopathy.
AB - That HTLV-I is not a latent infection is indicated by the detection of mRNA in
the peripheral blood and CNS of patients with HTLV-I infection and by the
persisting humoral and cellular immune responses. Indeed the frequency of anti
HTLV CTL is extremely high. The reduction in anti-TAX CTL frequency following
reduction in proviral load suggests that removal of viral antigen may result in a
reduced inflammatory response at least in peripheral blood and although the
clinical data should be interpreted with caution, perhaps in the CNS. Patients
with more advanced disease, and possibly fixed deficits may not benefit from
either anti-inflammatory or antiretroviral treatment. The patients with most to
gain are those with least deficit in whom early diagnosis and treatment will
depend on raising awareness of HTLV-I beyond the neurological community. Many
patients with HAM first present to a urologist or gynaecologist with bladder
dysfunction or may have been seen in the genitourinary clinical with impotence or
positive treponemal serology, which in the older patient is often the result of
childhood infection with Treponema pallidum pertenue. Investigation of these
patients should include HTLV-I serology and further investigation of HTLV-I
positive patients should include proviral load measurements as well as markers of
inflammation. Treatments whether antiviral or anti-inflammatory should be
assessed for their effect on both as well as a clinical response.
PMID- 10195026
TI - Patient referral outcome in gonorrhoea and chlamydial infections.
AB - OBJECTIVE: To describe the outcome of patient referral at the STD clinic of the
University Hospital Rotterdam. To study characteristics of heterosexual index
patients and partnerships related to referral outcome. METHODS: In 1994, patients
with gonorrhoea and chlamydia were referred to public health nurses for interview
and patient referral. Referral outcome was classified as "verified" if partners
attended the STD clinic and as "believed" if partners were said to have attended
elsewhere. RESULTS: Of 454 patients, 250 (55%) participated in the study. The
outcome of patient referral for the 502 eligible partners was 103 (20.5%)
verified referrals, 102 (20%) believed referrals, and 297 (59%) with unknown
follow up. Of the 103 partners examined, 43 had an STD of which 63% reported no
symptoms. The contact finding ratio was higher for chlamydia patients and
heterosexual men. Also, referral was more effective for index patients with
recent sexual contact, with follow up visits to the public health nurse, for men
who were not commercial sex worker (CSW) clients, and, to a lesser degree, for
Dutch patients and patients who sometimes used condoms. For steady partners,
referral was improved if the last sexual contact was more recent. Casual partners
visited the clinic more often if sexual contact occurred more than once, if the
last contact was more recent, if they were older, and if they were Dutch.
CONCLUSIONS: Patient referral was more effective for certain groups, such as
chlamydia patients and steady partners, but was inadequate for others, including
CSW and their clients, other "one night stands", young partners, and ethnic
minorities.
PMID- 10195027
TI - Effectiveness of patient delivered partner medication for preventing recurrent
Chlamydia trachomatis.
AB - OBJECTIVE: To determine if providing Chlamydia trachomatis infected women with
medication to deliver to their sex partner(s) could reduce recurrent chlamydia
infections compared with the standard partner referral method. STUDY DESIGN: A
observational cohort study of 178 women, 14-39 years old attending a family
planning clinic, diagnosed and treated for C trachomatis between October 1993 and
December 1994 was conducted (43 received patient delivered partner medication
(PDPM) and 135 received partner referral cards). Women were retested before or at
their annual visit. RESULTS: The mean time of follow up was 17.7 months (SD 7.7).
The PDPM group (n = 43) was similar to partner referral group (n = 135) for age,
race, contraceptive method, history of an STD, and follow up time. The annual
recurrent infection rate was lower among the PDPM group compared with the partner
referral group (11.5% v 25.5%, p < 0.05). After adjusting for age in logistic
regression, women in the PDPM group were less likely than women in the partner
referral group to have an incident C trachomatis infection (OR 0.37, 95% CI 0.15
0.97, p < 0.05). CONCLUSION: These findings suggest that patient delivered
partner medication can protect women from recurrent C trachomatis infection
compared with the standard partner referral approach. Prospective studies with
larger sample sizes are under way.
PMID- 10195028
TI - Psychological factors associated with recurrent vaginal candidiasis: a
preliminary study.
AB - OBJECTIVE: To identify psychological factors associated with chronic recurrent
vaginal candidiasis. DESIGN: A cross sectional exploratory study of women with
chronic, recurrent vaginal candidiasis. PATIENTS: 28 women found culture positive
and treated for vaginal candidiasis by a clinic physician at least twice within
the past 6 months. All women reported that they had experienced vaginal thrush
six or more times within 1 year. A comparison group comprised 16 women with no
history of recurrent vaginal candidiasis, of similar age range, and recruited
from a women's family planning service. METHODS: Both groups were compared on
demographic criteria, sexual health histories, mental health, and psychological
health characteristics. A purpose designed structured interview was administered
alongside a battery of standardised psychometric instruments measuring mood,
satisfaction with life, self esteem, and perceived stress. RESULTS: The two
groups showed considerable similarities, with no significant differences in
demographic characteristics and most sexual health issues. However, women with
recurrent vaginal candidiasis were significantly more likely to suffer clinical
depression, to be less satisfied with life, to have poorer self esteem, and to
perceive their lives as more stressful. Additionally, women with recurrent
vaginal candidiasis reported that their candidiasis seriously interfered with
their sexual and emotional relationships. CONCLUSIONS: Overall, this study
identified many areas of psychological morbidity associated with chronic vaginal
candidiasis, and indicates that development of appropriate psychological
treatment initiatives in this area is long overdue.
PMID- 10195029
TI - Heterosexual HIV transmission and STD prevalence: predictions of a theoretical
model.
AB - BACKGROUND: Previous studies suggest that concurrent sexually transmitted
infection may enhance HIV transmission. This paper explores some theoretical
consequences of this using a mathematical model of transmission of HIV and other
STD pathogens. OBJECTIVES: To develop a deterministic mathematical model to
describe the heterosexual transmission dynamics of both HIV and a bacterial STD.
STUDY DESIGN: We used survey derived estimates of sexual behaviour in a young
heterosexual London population in our deterministic mathematical model to
estimate the effects on an HIV epidemic of different levels of STD prevalence in
such a population. RESULTS: We show that the predictions of the model are
plausible and suggest that, even under conditions both of low STD prevalence and
of low HIV transmission enhancement, a substantial proportion of HIV transmission
events may be attributable to concurrent STD. CONCLUSIONS: It is likely that
epidemics of heterosexually transmitted HIV infection in industrialised countries
have been limited in size by the relative success of efforts to control STD. None
the less, a significant proportion of heterosexual transmission events which do
occur may be attributable to concurrent STD. In developing countries, cheap and
simple STD care is likely to be a highly cost effective strategy to prevent HIV
transmission.
PMID- 10195030
TI - Oral examination: a screening tool for HIV infection?
AB - OBJECTIVE: To estimate the predictive values for HIV infection of diagnosis of
oral manifestations of the infection. METHOD: Prevalence of oral manifestations
was compared in cross sectional blinded clinical examinations of homosexual men
attending a genitourinary medicine clinic. Data were extrapolated to populations
in England and Wales based on estimates of the prevalence of HIV infection.
RESULTS: Data were analysed for 572 HIV infected and non-infected men (312 and
260 respectively). Positive predictive values for erythematous candidiasis, hairy
leucoplakia and pseudomembranous candidiasis were greater than 0.96 at the
genitourinary medicine clinic and are estimated to be greater than 0.72 among
homosexual men in London. CONCLUSIONS: Clinical diagnoses of mucosal lesions
alone are poor predictors of HIV infection but are useful when used in
conjunction with a social history to establish if there are risk factors for
infection.
PMID- 10195032
TI - Immunoglobulin A, G, and M responses to L1 and L2 capsids of human papillomavirus
types 6, 11, 16, 18, and 33 L1 after newly acquired infection.
AB - OBJECTIVES: We performed a study to establish the pattern of serological
reactivity for immunoglobulins (Ig), to capsids of human papilloma virus (HPV)
after new HPV infection in two groups of subjects. METHODS: The pattern of
serological reactivity after acquisition of infection with HPV was investigated
by measuring IgA, IgM, and IgG antibodies to capsids containing L1 and L2
proteins of HPV types 6, 11, 16, 18, and 33 in longitudinal studies of groups
with different patterns of sexual activity. Individuals who tested negative for
HPV DNA by the polymerase chain reaction at enrolment, but who became HPV DNA
positive during follow up, were examined for antibodies to HPV capsids by enzyme
linked immunosorbent assay. One group consisted of 15 young girls (with eight
controls who remained HPV DNA negative) who were becoming sexually active and the
other comprised 12 male (with five controls) and 35 female (with seven controls)
heterosexual attenders of a sexually transmitted disease clinic who had had
multiple sexual partners. RESULTS: The sexually inexperienced girls showed IgA
and IgG responses, but seldom an IgM response to infection with HPV types 6/11,
16, and 18. No consistent pattern of serological reactivity was apparent for the
heterosexuals with multiple partners. The lack of association between current HPV
DNA positivity and detectable antibodies in these individuals was possibly
related to the duration of infection or to prior exposure to HPV. For the latter
group serological reactivity to HPV capsids was significantly greater in women
than in men (p = 0.001, p = 0.003, and p = 0.024, for IgG to HPV 6, 11, and 16,
respectively). CONCLUSION: The sex difference in antibody response detected in
previous studies with assays based on peptide antigens was thus corroborated in
the present study with capsid based serological assays. This sex difference might
reflect a difference in sexual activity and prior exposure to HPV between men and
women in this particular group.
PMID- 10195033
TI - How well is pelvic inflammatory disease managed in general practice? A postal
questionnaire survey.
AB - OBJECTIVE: Many patients with pelvic inflammatory disease (PID) present to their
general practitioners. Chlamydia trachomatis is the organism most commonly
implicated in this condition. This study aims to examine how well PID is managed
in the primary care setting and highlight areas for improvement. METHODS: The
study was performed by sending postal questionnaires to 180 randomly selected
general practitioners in Birmingham. Given the example of a woman presenting
clinically with PID, the doctors were asked questions on diagnosis and treatment.
To assess factors that may influence the answers, they were also asked about
their sex, year of qualification, and postgraduate training. RESULTS: 139
questionnaires (77%) were returned. 91.4% of the respondents feel confident in
managing patients with PID, and only 9.3% would usually refer these patients on.
However, 54.7% do not perform an endocervical swab for C trachomatis, 37.4% do
not include anti-chlamydial antibiotics in their treatment regimen, and 24.5% do
not advise sexual partners to be screened. Female doctors, those with higher
degrees, or obstetrics and gynaecology experience were more likely to give anti
chlamydial therapy, but no factors of the respondents significantly influenced
contact tracing behaviour. CONCLUSIONS: The management of a patient presenting
with PID should include investigation for C trachomatis and treatment with an
appropriate antibiotic. As PID is often a sexually transmitted disease, contact
tracing of sexual partners should be undertaken. The study suggests that a
significant proportion of general practitioners would not have offered optimal
management to patients with PID.
PMID- 10195031
TI - Tissue specific HPV expression and downregulation of local immune responses in
condylomas from HIV seropositive individuals.
AB - OBJECTIVE: To study the effect of tissue specific human papillomavirus (HPV)
expression and its effect on local immunity in condylomas from HIV positive
individuals. METHODS: Biopsy specimens of eight penile and eight perianal
condylomas from HIV seropositive individuals were analysed. Expression of viral
genes (HIV-tat and HPV E7 and L1) was determined by RT-PCR. The status of local
immunity also was determined by RT-PCR by measuring CD4, CD8, CD16, CD1a, HLA-DR,
and HLA-B7 mRNA levels in the tissues. Differentiation was determined by
measuring involucrin, keratinocyte transglutaminase, as well as cytokeratins 10,
16, and 17. Proliferation markers such as PCNA and c-myc were also determined.
RESULTS: The transcription pattern of HPV in perianal condylomas, which
preferentially expressed the early (E7) gene, was different from that of penile
condylomas, which primarily expressed the late (L1) gene. This transcription
pattern is in good correlation with the keratinisation and differentiation
patterns of the two epithelia: perianal biopsies preferentially expressed K16 and
K17 while penile warts mainly expressed K10, markers of parakeratotic and
orthokeratotic epithelia, respectively. Perianal biopsies also showed a higher
degree of proliferation (PCNA and c-myc). Interestingly, transcription of HIV-tat
was also higher in perianal than in penile biopsies. A high degree of local
immunodeficiency was observed in perianal biopsies--that is, levels of CD4, CD16,
and CD1a mRNAs were significantly lower. A negative correlation between CD1a
(Langerhans cells) levels and HPV E7 levels was established. HPV E7 levels
positively correlated with HIV-tat levels. Perianal tissues demonstrated more
CD1a depression and tat associated HPV upregulation. CONCLUSION: HIV influences
the expression of HPV genes resulting in local immunosuppression that might lead
to an inappropriate immune surveillance of viral infection. Also, tissue type is
an important factor in controlling viral transcription in a differentiation
dependent manner. These findings may explain the higher rate of dysplasia and
neoplasia in the perianal area.
PMID- 10195034
TI - Immunological functions of the human prepuce.
PMID- 10195036
TI - Hepatitis C: universal or selective screening?
PMID- 10195037
TI - Actual trends of the incidence of syphilis and gonorrhoea in the Slovak Republic
in the years 1990-6.
PMID- 10195035
TI - Male circumcision: assessment of health benefits and risks.
AB - OBJECTIVES: Globally approximately 25% of men are circumcised for religious,
cultural, medical, or parental choice reasons. However, controversy surrounds the
procedure, and its benefits and risks to health. We review current knowledge of
the health benefits and risks associated with male circumcision. METHODS: We have
used, where available, previously conducted reviews of the relation between male
circumcision and specific outcomes as "benchmarks", and updated them by searching
the Medline database for more recent information. RESULTS: There is substantial
evidence that circumcision protects males from HIV infection, penile carcinoma,
urinary tract infections, and ulcerative sexually transmitted diseases. We could
find little scientific evidence of adverse effects on sexual, psychological, or
emotional health. Surgical risks associated with circumcision, particularly
bleeding, penile injury, and local infection, as well as the consequences of the
pain experienced with neonatal circumcision, are valid concerns that require
appropriate responses. CONCLUSION: Further analyses of the utility and cost
effectiveness of male circumcision as a preventive health measure should, in the
light of this information, be research and policy priorities. A decision as to
whether to recommend male circumcision in a given society should be based upon an
assessment of the risk for and occurrence of the diseases which are associated
with the presence of the foreskin, versus the risk of the complications of the
procedure. In order for individuals and their families to make an informed
decision, they should be provided with the best available evidence regarding the
known benefits and risks.
PMID- 10195038
TI - Increased number of the cases of syphilis in Trabzon, a trade city in the Black
Sea region of Turkey.
PMID- 10195039
TI - Success of partner notification in heterosexuals with gonorrhoea: effects of sex
and ethnicity.
PMID- 10195040
TI - How common are sexually transmitted infections in the elderly?
PMID- 10195041
TI - Prospective analysis of STD related genital ulcers from Hamburg.
PMID- 10195042
TI - Public and personal health implications of asymptomatic viral shedding in genital
herpes.
PMID- 10195043
TI - Tuberculosis recommendations; a reply.
PMID- 10195045
TI - Control of STDs--the role of prophylactic vaccines against herpes simplex virus.
AB - OBJECTIVES: To summarise the current status of genital herpes simplex virus (HSV)
vaccine development and provide a discussion of the potential benefits and
limitations of genital herpes vaccines. METHODS: Literature review. RESULTS:
Genital herpes simplex virus infection has a complex pathogenesis that has
contributed to it becoming a serious worldwide problem. In an attempt to control
the problem five different types of genital herpes vaccines have been developed.
These include inactivated virion derived vaccines, adjuvanted subunit vaccines,
vectored vaccines, replication limited live viral vaccines, genetically
attenuated live viral vaccines, and nucleic acid vaccines. While available
commercially in some parts of the world, inactivated virion derived vaccines have
not been proved effective. Of the others, adjuvanted subunit vaccines,
replication limited live viral vaccines, and nucleic acid vaccines are currently
in clinical trials and vectored vaccines and genetically attenuated live viral
vaccines are in preclinical development. CONCLUSION: With regard to HSV vaccines
in general, it is reasonable to expect that the newer vaccines may protect the
individual from developing symptomatic genital herpes but may not protect against
asymptomatic viral infection. With widespread use HSV vaccines might help to
prevent the spread of genital herpes.
PMID- 10195046
TI - Sexual transmission and prevention of the hepatitis viruses A-E and G.
AB - OBJECTIVES: To assess current knowledge about the potential for sexual
transmission of the hepatitis viruses A-E and G and how to prevent any such
transmission. METHOD: A search of published literature identified through Medline
1966-June 1998 (Ovid v 3.0), the Cochrane Library and reference lists taken from
each article obtained. Textword and MeSH searches for hepatitis A, B, C, D, E, G,
delta, GB virus, GBV-C were linked to searches under the textword terms sex$,
vaccine$, prevent$, and MeSH subheadings, epidemiology, transmission, prevention,
and control. CONCLUSIONS: There is evidence for heterosexual transmission of
hepatitis B, C, D, and G and homosexual transmission of hepatitis A-D and G.
Condoms are an effective method for preventing transmission by penetrative
vaginal or anal sex although spread of types A and B are linked also to oro-anal
sex. Hepatitis types A and B can be prevented by pre- and post-exposure active or
passive immunisation. There is still some uncertainty about appropriate target
groups for pre-exposure vaccination, particularly against hepatitis A.
PMID- 10195048
TI - Behavioural intervention trials for HIV/STD prevention in schools: are they
feasible?
AB - OBJECTIVE: To assess the feasibility of conducting a large randomised controlled
trial (RCT) of peer led intervention in schools to reduce the risk of HIV/STD and
promote sexual health. METHODS: Four secondary schools in Greater London were
randomly assigned to receive peer led intervention (two experimental schools) or
to act as control schools. In the experimental schools, trained volunteers aged
16-17 years (year 12) delivered the peer led intervention to 13-14 year old
pupils (year 9). In the control schools, year 9 pupils received the usual teacher
led sex education. Questionnaire data collected from year 9 pupils at baseline
included views on the quality of sex education/intervention received, and
knowledge and attitudes about HIV/AIDS and other sexual matters. Focus groups
were also conducted with peer educators and year 9 pupils. Data on the process of
delivering sex education/intervention and on attitudes to the RCT were collected
for each of the schools. Analysis focused on the acceptability of a randomised
trial to schools, parents, and pupils. RESULTS: Nearly 500 parents were informed
about the research and invited to examine the study questionnaire; only nine
raised questions and only one pupil was withdrawn from the study. Questionnaire
completion rates were around 90% in all schools. At baseline, the majority of
year 9 pupils wanted more information about a wide range of sexual matters. Focus
group work indicated considerable enthusiasm for peer led education, among peer
educators and year 9 pupils. Class discipline was the most frequently noted
problem with the delivery of the peer led intervention. CONCLUSION: Evaluation of
a peer led behavioural intervention through an RCT can be acceptable to schools,
pupils, and parents and is feasible in practice. In general, pupils who received
the peer led intervention responded more positively than those in control
schools. A large RCT of the long term (5-7 year) effects of this novel
intervention on sexual health outcomes is now under way.
PMID- 10195047
TI - Sexual transmission of hepatitis C virus infection.
AB - BACKGROUND: Hepatitis C virus (HCV) is the cause of almost all cases of
parenterally transmitted non-A, non-B viral hepatitis (NANBH). HCV is an RNA
virus, unrelated to the hepatitis viruses, A, B, D, or E; it was first identified
in 1989. Although most infections become chronic, and it may lead to chronic
liver disease, most patients with HCV infection are asymptomatic. The predominant
modes of transmission are by blood, blood products, or other parenteral exposure,
particularly injecting drug use. More contentious is the role of sexual
transmission, although evidence for this was provided by studies of NANBH.
OBJECTIVE: This review considers the evidence for sexual transmission, and the
types of studies used to estimate the rate of transmission and the factors that
may influence it. METHOD: A Medline search using the keywords hepatitis C, sex,
transmission, and prevalence in MeSH and free text. References in papers were
searched, and some unpublished data identified. References were further selected
to illustrate different methodologies. FINDINGS: Evidence for sexual transmission
is provided by several types of study including prevalence studies in groups at
risk of other STDs, investigation of cases identified from surveillance reports,
and cross sectional and longitudinal partner studies. Many studies are limited by
their small size, the sensitivity and specificity of early assays, lack of
controls, or the difficulty of excluding other routes of transmission. One
prospective cohort study reported an incidence of 12 per 1000 person years in the
sexual partners of HCV infected patients. 1-3% of partners of HCV infected
patients are found to be infected in cross sectional studies. Co-infection with
HIV, duration of the relationship, or chronic liver disease may be independent
cofactors increasing the risk of transmission. A meta-analysis of selected
studies may be informative, and further larger prospective studies are required.
There is a small but definite risk of sexual transmission of hepatitis C.
PMID- 10195049
TI - Partner notification for gonorrhoea: a comparative study with a provincial and a
metropolitan UK clinic.
AB - OBJECTIVE: To compare partner notification practice and outcomes at a provincial
and a metropolitan clinic. DESIGN: Prospective study, following standardisation
of partner notification policy. SETTINGS: Sheffield Department of Genitourinary
Medicine, Royal Hallamshire Hospital and Jefferiss Wing Centre for Sexual Health,
St Mary's Hospital, London. SUBJECTS: Consecutive patients with culture positive
gonorrhoea between October 1994 and March 1996 who were interviewed by a health
adviser. RESULTS: In Sheffield, 235 cases reported 659 outstanding contacts, of
whom 129 (20%) were subsequently screened, and 65 (50%) had gonorrhoea. At St
Mary's 510 cases reported 2176 outstanding contacts, of whom 98 (5%) were known
to have been screened, and 53 (54%) had gonorrhoea. Patient or provider referral
agreements appeared more productive in Sheffield, where 60% resulted in contact
attendance, compared with 13% at St Mary's. Provider referral was used more
frequently in Sheffield, for 44% of referrals, compared with 1% at St Mary's.
Multivariate analysis showed that partner notification was less effective for
casual and short term (< 7 days) partnerships in both centres, and for homosexual
men at St Mary's. CONCLUSION: Partner notification outcomes were better in the
provincial setting where contact attendance could be recorded more reliably and
provider referral was used more extensively. The high proportion of contacts who
remained untraced in both settings indicates the need for complementary screening
and prevention initiatives.
PMID- 10195050
TI - Prevalence of HIV-1 among attenders at sexually transmitted disease clinics:
analyses according to country of birth.
AB - OBJECTIVES: To determine the importance of world region of birth as a risk factor
for HIV-1 infection, the likelihood of having an HIV-1 infection diagnosed and
the likelihood of having another coexisting acute sexually transmitted infection
(STI) among attenders at genitourinary medicine clinics. SUBJECTS: Specimens from
attenders having routine syphilis serology at 15 sexually transmitted disease
clinics in England, Wales, and Northern Ireland participating in the unliked
anonymous seroprevalence monitoring programme from 1994 to 1996. METHODS: Limited
data were collected with specimens that were irreversibly unlinked from the
source patients before testing for antibodies to HIV-1. Numbers of specimens, the
prevalence of HIV-1, the proportions of infections clinically diagnosed, and the
presence of coexisting acute STIs were analysed according to world region of
birth, sexual orientation, and injecting drug use. RESULTS: Between 1994 and
1996, 173,075 specimens were collected; 16.9% were from people born outside the
United Kingdom. Risk of being HIV-1 positive was significantly higher overall for
both men and women born abroad, but this was not the case for those born in south
Asia (India, Pakistan, and Bangladesh). Homosexual and bisexual males born abroad
were almost twice as likely to be HIV infected as their counterparts born in the
United Kingdom. However, homosexual and bisexual men born in the United Kingdom
accounted for almost three quarters of the 1174 HIV-1 positive specimens
detected. Among 158,728 non-drug injecting heterosexuals the highest prevalence
was observed in specimens from those men (4.0%) and women (5.8%) born in sub
Saharan Africa. The 6991 heterosexual men and women born in other European
countries were also more likely to provide HIV-1 positive specimens than UK born
heterosexuals. However, 39% of the HIV-1 positive specimens in heterosexuals come
from clinic attenders born in the United Kingdom. Heterosexual males were
generally less likely to have their infection diagnosed than females. There were
182 attendances (mostly from London clinics) non-drug injecting heterosexual men
and women who were infected with both HIV-1 and an acute sexually transmitted
infection; only 12% of whom had had their HIV-1 infection diagnosed. CONCLUSION:
Among most people attending genitourinary medicine clinics, being born abroad is
associated with an increased likelihood for HIV-1 infection. HIV-1 infected
heterosexuals, of whom 46% are people from sub-Saharan Africa, are unlikely to
have their infection clinically diagnosed and thus are unable to obtain
appropriate treatment. The presence of HIV-1 infected heterosexual men and women
with acute STI represents a potential source of heterosexual HIV transmission
both for those born in the United Kingdom and born abroad.
PMID- 10195051
TI - Asymptomatic non-ulcerative genital tract infections in a rural Ugandan
population.
AB - OBJECTIVE: To document the prevalence of asymptomatic non-ulcerative genital
tract infections (GTI) in a rural African cohort. METHODS: The study population
consisted of all adults aged 15-59 residing in 56 rural communities of Rakai
District, southwest Uganda, enrolled in the Rakai STD Control for AIDS Prevention
Study. Participants were interviewed about the occurrence of vaginal or urethral
discharge and frequent or painful urination in the previous 6 months. Respondents
were asked to provide blood and a first catch urine sample. Serum was tested for
HIV-1. Urine was tested with ligase chain reaction (LCR) for N gonorrhoeae and C
trachomatis. Women provided two self administered vaginal swabs; one for T
vaginalis culture and the other for a Gram stained slide for bacterial vaginosis
(BV) diagnosis. RESULTS: A total of 12,827 men and women were enrolled. Among
5140 men providing specimens, 0.9% had gonorrhoea and 2.1% had chlamydia. Among
6356 women, 1.5% had gonorrhoea, 2.4% had chlamydia, 23.8% were infected with
trichomonas and 50.9% had BV.53% of men and 66% of women with gonorrhoea did not
report genital discharge or dysuria at anytime within the previous 6 months. 92%
of men and 76% of women with chlamydia and over 80% of women with trichomonas or
BV were asymptomatic. The sensitivities of dysuria or urethral discharge for
detection of infection with either gonorrhoea or chlamydia among men were only
21.4% and 9.8% respectively; similarly, among women the sensitivity of dysuria
was 21.0% while that of vaginal discharge was 11.6%. For trichomonas or BV the
sensitivity of dysuria was 11.7% and that of vaginal discharge was 10.5%.
CONCLUSION: The prevalence of non-ulcerative GTIs is very high in this rural
African population and the majority are asymptomatic. Reliance on reported
symptoms alone would have missed 80% of men and 72% of women with either
gonorrhoea or chlamydia, and over 80% of women with trichomonas or BV. To achieve
STD control in this and similar populations public health programmes must target
asymptomatic infections.
PMID- 10195052
TI - Risk factors for laparoscopically confirmed pelvic inflammatory disease: findings
from Mumbai (Bombay), India.
AB - OBJECTIVES: Sexually transmitted diseases (STDs) are an important cause of pelvic
inflammatory disease (PID) but have often not been detected in microbiological
studies of Indian women admitted to hospital gynaecology wards or private
clinics. In this cross sectional study, women living in the inner city of Mumbai
(Bombay) were investigated for socioeconomic, clinical, and microbiological risk
factors for PID. METHODS: Microbiological tests and laparoscopic examination were
carried out on 2736 women aged < or = 35 years who came to a health facility with
suspected acute salpingitis or infertility or for laparoscopic sterilisation. 86
women with a clinical diagnosis of PID were not referred for laparoscopy although
their characteristics are described. Associations between various risk factors
and PID status were investigated and logistic regression performed on all factors
that remained significant. RESULTS: Of women with a laparoscopically confirmed
evaluation, 26 women had acute and 48 chronic pelvic infection. Independent risk
factors for PID were later age at menarche (> or = 14 years), a history of
stillbirth and no previous pregnancy, history of tuberculosis, STD, dilatation
and curettage or previous laparoscopy, and presence of Gardnerella vaginalis.
CONCLUSIONS: It is concluded that STD related risk factors applied to only a
small proportion of PID cases and that other determinants of PID are important,
including obstetric complications, invasive surgical procedures such as
laparoscopy, and tuberculosis.
PMID- 10195053
TI - Contraceptive needs of women attending a genitourinary medicine clinic for the
first time.
AB - OBJECTIVE: To assess the need for, and potential uptake of, a contraceptive
service within a genitourinary medicine (GUM) clinic. METHODS: 544 women, median
age 17 years (range 13-54) including 142 teenagers, attending the Fife GUM
clinics serving a semirural population of 350,000 for the first time in the 12
month period from 1 September 1995 to 31 August 1996 were interviewed. RESULTS:
Contraception was required by 353, of whom only 5% (29) were at risk of unplanned
pregnancy, although half (15) of these were teenagers. 23 of 29 (79%) stated that
they would access contraception at a GUM clinic if it were available. Of women
using contraception, 67% (217/324) were taking the oral contraceptive pill (OCP),
of whom 177 obtained supplies from their general practitioners and were happy
with this. However, 92/177 (52%) stated that they would access the OCP at GUM
clinics if it were available. Overall, of the 243 women who stated that they
would access contraception at the GUM clinic, 23 of whom were currently at risk
of an unplanned pregnancy, the demand was principally for condoms and the OCP.
CONCLUSION: The majority of women attending GUM clinics for the first time are
using contraception, or have deliberately chosen not to do so. Only 5% were at
risk of unplanned pregnancy. In general, the women using contraception were happy
with their current source of contraception, but about two thirds would use a
contraceptive service at GUM clinics if it were available at the time they were
attending the clinic. It was found that teenagers accounted for half of those
women at risk of unwanted pregnancy. However, the majority of teenagers requiring
contraception would consider obtaining it from GUM clinics.
PMID- 10195054
TI - Detection of Chlamydia trachomatis in vaginal specimens from female commercial
sex workers using a new improved enzyme immunoassay.
AB - OBJECTIVE: To evaluate the performance of a new improved enzyme immunoassay (EIA)
kit for the detection of Chlamydia trachomatis in vaginal swab and endocervical
swab specimens from female commercial sex workers, in comparison with a
conventional EIA test and a polymerase chain reaction (PCR) assay. METHODS: A
high risk group of 163 female commercial sex workers who visited a sexually
transmitted disease (STD) clinic in order to undergo screening for major STDs,
including chlamydial infection, were enrolled. A total of four swab specimens,
including two vaginal and two endocervical specimens, were collected from each
woman by a clinician. To identify C trachomatis, a new improved EIA kit (IDEIA
PCE), a conventional EIA kit (IDEIA), and PCR assay (Amplicor) were used.
Discrepancies in the results were resolved using supplementary PCR assay. A
female patient was considered to be infected with C trachomatis if the IDEIA PCE
test and PCR test for both sample sites (endocervical and vaginal) gave positive
results. Following resolution of these discrepancies, relative sensitivity and
specificity, confidence intervals, and predictive values for each type of
specimen by each assay were calculated. RESULTS: Of the 163 women tested, 35
(21.5%) were shown to be infected with C trachomatis. The relative sensitivities
in vaginal swab specimens were 88.8%, 68.6%, and 91.4% using IDEIA PCE, IDEIA,
and PCR, respectively. The relative specificities in vaginal swab specimens were
99.2%, 99.2%, and 100%, respectively. The relative sensitivities in endocervical
swab specimens were 85.7%, 77.1%, and 91.4% with IDEIA PCE, IDEIA, and PCR,
respectively. The relative specificities in endocervical swab specimens were all
100%. CONCLUSIONS: The results obtained in this study suggest that the
sensitivity and specificity of IDEIA PCE test on vaginal swab and endocervical
swab specimens were similar to those of PCR assay on the two types of specimen.
It is concluded that IDEIA PCE test on vaginal swab specimens is an acceptable,
sensitive, and less invasive approach for the detection of C trachomatis in
commercial sex workers with a high prevalence of C trachomatis infection.
PMID- 10195055
TI - Fever, weight loss, and night sweats: infection or malignancy?
PMID- 10195056
TI - Where young people with multiple sexual partners seek medical care: implications
for screening for chlamydial infection.
AB - OBJECTIVE: To investigate among young people the relation between the number of
sexual partners and use of medical services in order to guide planning of
sexually transmitted disease screening. DESIGN: Cross sectional study within a
birth cohort using a questionnaire presented by computer. SETTING: Dunedin, New
Zealand in 1993-4. SUBJECTS: 477 men and 458 women aged 21 enrolled in the
Dunedin Multidisciplinary Health and Development Study, comprising 91.7% of
survivors of the cohort. RESULTS: Men with multiple sexual partners in the
previous year were less likely to have a general practitioner than men with one
or no partners (76.2% v 88.5%, p < 0.01). Among the women the respective
proportions (83.1% and 88.4%) were not significantly different. Significantly
more women than men (75.8% v 50.7%, p = 0.03) with five or more partners in the
previous year had visited their own general practitioner over that period. Among
the sexually experienced, more women than men attended any setting appropriate
for sexually transmitted disease screening (93.6% v 71.6%, p < 0.001).
CONCLUSIONS: In New Zealand a screening programme for sexually transmitted
diseases among young adults reliant on invitation by their own general
practitioner would be biased towards those at less risk. Opportunistic screening
in general practice would potentially include only about half the most sexually
active men and three quarters of such women over a 12 month period. The extension
of opportunistic screening to other settings considered appropriate for
discussion of sexual health issues could potentially engage the vast majority of
women, but not men, at most risk. Any screening programme should incorporate an
effective method of finding and treating the sexual partners of infected women.
PMID- 10195057
TI - Low prevalence of hepatitis B markers among Mexican female sex workers.
AB - OBJECTIVES: To estimate the prevalence and associated risk factors of hepatitis B
virus (HBV) serological markers in female sex workers (FSW) in Mexico City.
METHODS: The study population consisted of 1498 FSW who attended a detection
centre for human immunodeficiency virus (HIV) in Mexico City, between January and
October 1992. Study participants responded to a standardised questionnaire and
provided a blood sample for serology of syphilis, HIV, and HBV. RESULTS: A total
of 0.2% (95% CI 0.1-0.3) of the population were hepatitis B surface antigen
(HBsAg) carriers. The general prevalence of antibodies to hepatitis B core
antigen (anti-HBc) was 6.3% (95% CI 5.5-7.1). This marker of previous exposition
to HBV, was independently associated by logistic regression multivariate analysis
with age, working in the street, and history of blood transfusion (BT) before
1987 (OR 4.8, 95% CI 2.1-11.3). Syphilis prevalence was 7.6% (95% CI 6.2-8.9) and
HIV prevalence was 0.1% (95% CI 0-0.3). CONCLUSIONS: The prevalence of HBV
infection in this group of Mexican FSW is lower than previously reported in other
countries. In addition, the frequency of HBsAg carriers is similar to that in the
general Mexican population. The absence of two major risk factors for HBV
transmission in this group of FSW--that is, injecting drug use and anal
intercourse, could help to explain this finding. However, the positive
association between anti-HBc and history of blood transfusion demonstrated here,
highlights the need to reinforce strict control of blood supplies in Mexico.
PMID- 10195058
TI - Gonococcal scalp abscess in a neonate delivered by caesarean section.
AB - Gonococcal infection in caesarean delivered babies is very rare and is usually
limited to ophthalmia neonatorum. The mother had rupture of membranes 14 hours
before the caesarean section. The infection was most likely introduced by the
fetal scalp electrode probes applied 2 hours before delivery. This is the first
reported of a neonatal gonococcal abscess in a caesarean delivered infant.
PMID- 10195059
TI - Services in genitourinary medicine: hospital and primary care sites have
different patient populations.
PMID- 10195060
TI - Early lipodystrophy occurring during post-exposure prophylaxis.
PMID- 10195061
TI - Recurrent bacterial vaginosis and metronidazole resistance in Gardnerella
vaginalis.
PMID- 10195062
TI - Cutaneous horn of glans penis.
PMID- 10195063
TI - The case against routine HPV testing in cervical screening.
PMID- 10195064
TI - Influence of genital infection on cervical cytology.
PMID- 10195065
TI - Influence of genital infection on cervical cytology.
PMID- 10195066
TI - DNase in cystic fibrosis: the challenge of assessing response and maximising
benefit.
PMID- 10195067
TI - Societal and health care benefits of early use of inhaled steroids.
PMID- 10195068
TI - Augmentation therapy for severe alpha 1-antitrypsin deficiency: is the jury still
out on a trial?
PMID- 10195069
TI - Effects of formoterol on histamine induced plasma exudation in induced sputum
from normal subjects.
AB - BACKGROUND: A number of studies have shown that beta 2 agonists, including
formoterol, inhibit plasma exudation induced by the inflammatory stimulus in
animal airways. Whether clinical doses of beta 2 agonists inhibit plasma
exudation in human bronchial airways is unknown. METHODS: In order to explore the
microvascular permeability and its potential inhibition by beta 2 agonists in
human bronchial airways a dual induction method was developed: plasma exudation
induced by histamine inhalation followed by sputum induction by hypertonic saline
(4.5%) inhalation. Sixteen healthy subjects received formoterol (18 micrograms)
in a placebo controlled, double blind, crossover study. Sputum was induced on
five occasions: once at baseline and four times after histamine challenge (30
minutes and eight hours after both formoterol and placebo treatments). Sputum
levels of alpha 2-macroglobulin were determined to indicate microvascular
epithelial exudation of bulk plasma. RESULTS: Histamine induced plasma exudation
30 minutes after placebo was considerably greater than at baseline (median
difference 11.3 micrograms/ml (95% confidence interval 0.9 to 90.0)). At 30
minutes after formoterol the effect of histamine was reduced by 5.1 (0.9 to 61.9)
micrograms/ml compared with placebo. At eight hours histamine produced less
exudation and inhibition by formoterol was not demonstrated. CONCLUSION: This
study shows for the first time an anti-exudative effect of a beta 2 agonist in
healthy human bronchial airways. Through its physical and biological effects,
plasma exudation is of multipotential pathogenic importance in asthma. If the
present findings translate to disease conditions, it suggests that an anti
exudative effect may contribute to the anti-asthmatic activity of formoterol.
PMID- 10195070
TI - Long-term effects of aerosolised rhDNase on pulmonary disease progression in
patients with cystic fibrosis.
AB - BACKGROUND: After multiple studies, including clinical trials, suggested some
mild clinical benefits from the use of rhDNase by patients with cystic fibrosis,
a widespread acceptance of the drug has followed. However, long-term effects,
specifically on lung disease progression, have not been demonstrated. Experience
with the use of this drug in a single cystic fibrosis centre is presented and
compared with the trends seen in the patient population of the centre before the
introduction of the drug. METHODS: Patients with cystic fibrosis routinely
followed at the University of Minnesota Cystic Fibrosis Center and prescribed
rhDNase for at least two years were included in this retrospective study. Data on
spirometric parameters (FEV1 and FEV1/FVC), allometric index, and admissions to
hospital were retrieved from the centre's database for the two years preceding
the prescription of rhDNase and the two years that followed. Trends in pulmonary
function and allometric index were analysed by mixed linear modelling, and
hospital admission rates for both periods were calculated and compared. RESULTS:
One hundred and ninety patients met the inclusion criteria for the study. In the
two years preceding the prescription of rhDNase the trends noted were those of a
mild decline in FEV1, a stable FEV1/FVC, and a mild improvement in allometric
index. In the two years that followed the prescription of rhDNase a mild decline
in all these parameters occurred which was a significant change from the previous
period (all p < 0.009). There was no difference between females and males in the
trends experienced after the start of rhDNase. By logistic regression analysis
only the presence of malnutrition at the time of prescription was associated with
a positive trend after the introduction of rhDNase. No significant change in the
hospital admission rates occurred, with rates of 0.52 (0.16) and 0.56 (0.21)
admissions/patient/year for the periods before and after the prescription of
rhDNase, respectively. CONCLUSIONS: The introduction of rhDNase to the regimen of
patients with cystic fibrosis cared for at this centre has not been followed by a
positive trend in lung function and nutritional parameters. There are some
differences between this patient population and those who participated in
previous studies which may help to explain the contrasting findings of this
study. However, it is also possible that factors other than mucus clearance need
to be improved to achieve a favourable response in disease progression. Patients
on this treatment should be followed closely and the benefit judged on an
individual basis. More studies are needed to define better the specific
indications and use of this form of treatment.
PMID- 10195071
TI - Contribution of genetic factors other than CFTR to disease severity in cystic
fibrosis.
AB - BACKGROUND: Disease severity in patients with cystic fibrosis shows marked
variability. Attempts to explain this phenotypic heterogeneity on the basis of
CFTR genotype have had limited success. A study was undertaken to test the
hypothesis that naturally occurring variants of the pro-inflammatory cytokine
tumour necrosis factor alpha (TNF-alpha) and the detoxifying enzyme glutathione S
transferase M1 (GSTM1) could influence disease severity in cystic fibrosis.
METHODS: Fifty-three children with cystic fibrosis were studied. To allow for the
effect of age, all clinical details were collected during the eighth year of age.
The subjects were divided into groups, both according to the presence or absence
of the TNF2 TNF-alpha -308 promoter polymorphism (n = 20), and by homozygosity
for the null allele of GSTM1 (n = 26). RESULTS: Percentage predicted forced
expiratory volume in one second (FEV1) and weight z scores were significantly
lower in the TNF2 group (mean difference (95% confidence intervals) for FEV1
11.6% (1.7 to 21.5) and 0.59 (0.06 to 1.12) for weight z score). The Chrispin
Norman chest radiographic score was significantly higher and the Shwachman score
was significantly lower in patients homozygous for the GSTM1 null allele.
CONCLUSIONS: Two independent genetic factors have been identified which appear to
influence disease severity in cystic fibrosis. These results support the
contention that inflammation in cystic fibrosis contributes to tissue damage.
Isolation of further such factors may lead to identification of patients at risk
of more severe disease and allow targeted aggressive therapy in this group.
PMID- 10195072
TI - Alpha-1 antitrypsin deficiency alleles and severe cystic fibrosis lung disease.
AB - BACKGROUND: Alpha-1 antitrypsin (alpha 1-AT) is the most abundant proteinase
inhibitor within the lung. We have recently reported the surprising observation
that cystic fibrosis patients with mild to moderate deficiency of alpha 1
antitrypsin have significantly better pulmonary function than non-deficient
patients. This study may have been biased as it did not include the most severely
affected patients who have died in childhood or those who have undergone
orthotopic lung transplantation. The prevalence of alpha 1-antitrypsin deficiency
alleles in this most severely affected group of patients with cystic fibrosis was
therefore assessed. METHODS: DNA was obtained from neonatal blood spots from
children with cystic fibrosis who had died from pulmonary disease and from
formalin fixed lung tissue from transplanted cystic fibrosis patients. The common
S and Z deficiency alleles of alpha 1-AT were sought by amplification mutagenesis
of the appropriate region of the alpha 1-AT gene followed by restriction enzyme
digestion with Xmn I and Taq I, respectively. RESULTS: Seventy-nine patients were
identified (seven dead, 72 transplanted). Two patients (2.5%) were heterozygous
for the Z allele of alpha 1-AT and four (5.1%) were heterozygous for the S
allele. This is not significantly different from the incidence in the normal
population of 4% and 8% for the S and Z alleles, respectively. CONCLUSIONS: These
data support previous findings that deficiency of alpha 1-AT is not associated
with more severe pulmonary disease in cystic fibrosis and may be associated with
milder lung disease. Further work is needed to clarify the mechanisms underlying
the progressive lung damage in cystic fibrosis.
PMID- 10195073
TI - First treatment with inhaled corticosteroids and the prevention of admissions to
hospital for asthma.
AB - BACKGROUND: Early treatment with inhaled corticosteroids appears to improve
clinical symptoms in asthma. Whether a first treatment initiated in the year
following the recognition of asthma can prevent major outcomes such as admission
to hospital has yet to be studied. METHODS: A case-control study nested within a
cohort of 13,563 newly treated asthmatic subjects selected from the databases of
Saskatchewan Health (1977-1993) was undertaken to investigate the effectiveness
of a first treatment with inhaled corticosteroids in preventing admissions to
hospital for asthma. Study subjects were aged between five and 44 years at cohort
entry. First time users of inhaled corticosteroids were compared with first time
users of theophylline for a maximum of 12 months of treatment. The two treatments
under study were further classified into initial and subsequent therapy to
minimize selection bias and confounding by indication. Odds ratios associated
with hospital admissions for asthma were estimated using conditional logistic
regression. Markers of asthma severity, as well as age and sex, were considered
as potential confounders. RESULTS: Three hundred and three patients admitted to
hospital with asthma were identified and 2636 matched controls were selected.
subjects initially treated with regular inhaled corticosteroids were 40% less
likely to be admitted to hospital for asthma than regular users of theophylline
(odds ratio 0.6; 95% CI 0.4 to 1.0). The odds ratio decreased to 0.2 (95% CI 0.1
to 0.5) when inhaled corticosteroids and theophylline were given subsequently.
CONCLUSION: The first regular treatment with inhaled corticosteroids initiated in
the year following the recognition of asthma can reduce the risk of admission to
hospital for asthma by up to 80% compared with regular treatment with
theophylline. This is probably due, at least in part, to reducing the likelihood
of a worsening in the severity of asthma.
PMID- 10195074
TI - Increase in exhaled nitric oxide levels in patients with difficult asthma and
correlation with symptoms and disease severity despite treatment with oral and
inhaled corticosteroids. Asthma and Allergy Group.
AB - BACKGROUND: Patients with difficult asthma suffer chronic moderate to severe
persistent asthma symptoms despite high doses of inhaled and oral corticosteroid
therapy. These patients suffer a high level of treatment and disease related
morbidity but little is known about the degree of airway inflammation in these
patients. METHODS: Fifty two patients were examined to assess levels of exhaled
nitric oxide (NO) as a surrogate marker of inflammatory activity in this
condition. From this group, 26 patients were defined with severe symptoms and
current physiological evidence of reversible airway obstruction requiring high
dose inhaled (> or = 2000 micrograms beclomethasone dipropionate (BDP)
equivalent) or oral steroid therapy to maintain disease control. RESULTS: Exhaled
NO levels were higher in subjects with difficult asthma (mean 13.9 ppb, 95% CI
9.3 to 18.5) than in normal controls (7.4 ppb, 95% CI 6.9 to 7.8; p < 0.002), but
lower than levels in steroid naive mild asthmatics (36.9 ppb, 95% CI 34.6 to
39.3; p < 0.001). Prednisolone treated patients had higher exhaled NO levels than
patients only requiring inhaled corticosteroids (17.5 ppb, 95% CI 11.1 to 24.0
versus 7.2 ppb, 95% CI 4.6 to 9.8; p = 0.016), suggesting greater disease
severity in this group. Non-compliance with prednisolone treatment was observed
in 20% of patients but this did not explain the difference between the treatment
groups. Exhaled NO levels were closely correlated with symptom frequency (p =
0.03) and with rescue beta agonist use (p < 0.002), but they did not correlate
with lung function. CONCLUSIONS: Exhaled NO may serve as a useful complement to
lung function and symptomatology in the assessment of patients with chronic
severe asthma, and in the control and rationalisation of steroid therapy in these
patients.
PMID- 10195075
TI - Effect of dampness at home in childhood on bronchial hyperreactivity in
adolescence.
AB - BACKGROUND: Relatively little is known about risk factors for the persistence of
asthma and respiratory symptoms from childhood into adolescence, and few studies
have included objective measurements to assess outcomes and exposure. METHODS:
From a large cross sectional study of all 4th grade school children in Munich
(mean age 10.2 years), 234 children (5%) with active asthma were identified. Of
these, 155 (66%) were reinvestigated with lung function measurements and
bronchial provocation three years later (mean age 13.5 years). RESULTS: At follow
up 35.5% still had active asthma. Risk factors for persisting asthma symptoms in
adolescence were more severe asthma (OR 4.94; CI 1.65 to 14.76; p = 0.004) or
allergic triggers (OR 3.54; CI 1.41 to 8.92; p = 0.007) in childhood. Dampness
was associated with increased night time wheeze and shortness of breath but not
with persisting asthma. Risk factors for bronchial hyperreactivity in adolescence
were bronchial hyperreactivity in childhood (p = 0.004), symptoms triggered by
allergen exposure (OR 5.47; CI 1.91 to 25.20; p = 0.029), and damp housing
conditions (OR 16.14; CI 3.53 to 73.73; p < 0.001). In a subgroup in whom house
dust mite antigen levels in the bed were measured (70% of the sample), higher
mite antigen levels were associated with bronchial hyperreactivity (OR per
quartile of mite antigen 2.30; CI 1.03 to 5.12; p = 0.042). Mite antigen levels
were also significantly correlated with dampness (p = 0.05). However, the effect
of dampness on bronchial hyperreactivity remained significant when adjusting for
mite allergen levels (OR 5.77; CI 1.17 to 28.44; p = 0.031). CONCLUSION: Dampness
at home is a significant risk factor for the persistence of bronchial
hyperreactivity and respiratory symptoms in children with asthma. This risk is
only partly explained by exposure to house dust mite antigen.
PMID- 10195076
TI - Exposure of healthy volunteers to swine house dust increases formation of
leukotrienes, prostaglandin D2, and bronchial responsiveness to methacholine.
AB - BACKGROUND: Acute exposure of healthy subjects to swine house dust causes
increased bronchial responsiveness to methacholine but no acute
bronchoconstriction. The role of cysteinyl leukotrienes and mast cells in
increased bronchial responsiveness is unclear. METHODS: Ten non-asthmatic
subjects were exposed to swine dust for three hours while weighing pigs in a
piggery. Urine was collected prior to and for up to 12 hours after entering the
piggery and at the same times five days before and the day after exposure. As
indices of whole body leukotriene production and mast cell activation, urinary
levels of leukotriene E4 (LTE4) and 9 alpha, 11 beta-PGF2, the earliest appearing
urinary metabolite of prostaglandin D2 (PGD2), were measured. Bronchial
responsiveness to methacholine was determined five days before and the day after
the exposure. RESULTS: Methacholine PD20FEV1 decreased from 1.32 mg (95% CI 0.22
to 10.25) before exposure to 0.38 mg (95% CI 0.11 to 1.3) after exposure (p <
0.01). Associated with the increase in bronchial responsiveness there was a
significant mean difference between post- and prechallenge levels of LTE4
(difference 38.5 ng/mmol creatinine (95% CI 17.2 to 59.8); p < 0.01) and 9 alpha,
11 beta-PGF2 (difference 69 ng/mmol creatinine (95% CI 3.7 to 134.3); p < 0.05)
on the day of exposure to swine dust. Swine dust exposure induced a 24-fold
increase in the total cell number and a 12-fold increase in IL-8 levels in the
nasal lavage fluid. The levels of LTB4 and LTE4 in nasal lavage fluid following
exposure also increased 5.5-fold and 2-fold, respectively. CONCLUSIONS: The
findings of this study indicate that cysteinyl leukotrienes and other mast cell
mediators contribute to the development of increased bronchial responsiveness
following inhalation of organic swine dust.
PMID- 10195077
TI - Inflammatory response after inhalation of bacterial endotoxin assessed by the
induced sputum technique.
AB - BACKGROUND: Organic dusts may cause inflammation in the airways. This study was
performed to assess the usefulness of the induced sputum technique for evaluating
the presence of airways inflammation using inhaled endotoxin (lipopolysaccharide)
as the inducer of inflammation. METHODS: To characterise the inflammatory
response after inhalation of endotoxin, 21 healthy subjects inhaled 40 micrograms
lipopolysaccharide and were examined before and 24 hours after exposure.
Examinations consisted of a questionnaire for symptoms, spirometric testing,
blood sampling, and collection of induced sputum using hypertonic saline. Eleven
of the subjects inhaled hypertonic saline without endotoxin exposure as controls.
Cell counts, eosinophilic cationic protein (ECP), and myeloperoxidase (MPO) were
determined in blood and sputum. RESULTS: A significantly higher proportion of
subjects reported respiratory and general symptoms after endotoxin inhalation.
MPO and the number of neutrophils in the blood were higher and spirometric values
were decreased after the lipopolysaccharide challenge. In the sputum MPO, ECP,
and the numbers of neutrophils and lymphocytes were higher after the
lipopolysaccharide challenge. No significant differences were found after the
inhalation of hypertonic saline compared with before, except for a significantly
lower number of lymphocytes in the sputum. CONCLUSIONS: The results support
previous studies that inhaled endotoxin causes an inflammation at the exposure
site itself, as well as general effects. Sampling of sputum seems to be a useful
tool for assessing the presence of airways inflammation, and the inhalation of
hypertonic saline used to induce sputum did not significantly interfere with the
results found after inhalation of lipopolysaccharide.
PMID- 10195078
TI - Cross-colonisation with Pseudomonas aeruginosa of patients in an intensive care
unit.
AB - BACKGROUND: Ventilator-associated pneumonia (VAP) caused by Pseudomonas
aeruginosa is usually preceded by colonisation of the respiratory tract. During
outbreaks, colonisation with P aeruginosa is mainly derived from exogenous
sources. The relative importance of different pathways of colonisation of P
aeruginosa has rarely been determined in non-epidemic settings. METHODS: In order
to determine the importance of exogenous colonisation, all isolates of P
aeruginosa obtained by surveillance and clinical cultures from two identical
intensive care units (ICUs) were genotyped with pulsed field gel electrophoresis.
RESULTS: A total of 100 patients were studied, 44 in ICU 1 and 56 in ICU 2.
Twenty three patients were colonised with P aeruginosa, seven at the start of the
study or on admission and 16 of the remaining 93 patients became colonised during
the study. Eight patients developed VAP due to P aeruginosa. The incidence of
respiratory tract colonisation and VAP with P aeruginosa in our ICU was similar
to that before and after the study period, and therefore represents an endemic
situation. Genotyping of 118 isolates yielded 11 strain types: eight in one
patient each, two in three patients each, and one type in eight patients. Based
on chronological evaluation and genotypical identity of isolates, eight cases of
cross-colonisation were identified. Eight (50%) of 16 episodes of acquired
colonisation and two (25%) of eight cases of VAP due to P aeruginosa seemed to be
the result of cross-colonisation. CONCLUSIONS: Even in non-epidemic settings
cross-colonisation seems to play an important part in the epidemiology of
colonisation and infection with P aeruginosa.
PMID- 10195079
TI - Urinary cGMP concentrations in severe primary pulmonary hypertension.
AB - BACKGROUND: Prognostic evaluation of patients with primary pulmonary hypertension
(PPH) requires right heart catheterisation. The development of accurate non
invasive methods for monitoring these patients remains an important task. Cyclic
guanosine monophosphate (cGMP) is an indicator of the action of natriuretic
peptides and nitric oxide on target cells. Plasma and urinary cGMP concentrations
are raised in patients with congestive heart failure in whom they correlate
closely with haemodynamic parameters and disease severity. The aim of the present
study was to determine whether the urinary concentration of cGMP could be used as
a non-invasive marker of haemodynamic impairment in patients with severe PPH.
METHODS: Urinary cGMP concentrations were measured in 19 consecutive patients
with PPH, seven with acute asthma, and 30 normal healthy controls. RESULTS:
Patients with PPH had higher urinary cGMP concentrations than asthmatic patients
or normal healthy controls (p = 0.001). Urinary cGMP concentrations were higher
in patients with severe haemodynamic impairment--that is, those with a cardiac
index (CI) of < or = 2 l/min/m2 (p = 0.002)--and urinary cGMP concentrations were
inversely correlated with CI (r = -0.69, p = 0.002) and venous oxygen saturation
(r = -0.65, p = 0.003). CONCLUSION: Urinary cGMP concentrations may represent a
non-invasive indicator of the haemodynamic status of patients with severe PPH.
PMID- 10195080
TI - Glucocorticoid insensitive asthma: a one year clinical follow up pilot study.
AB - BACKGROUND: Glucocorticoid resistant or insensitive asthmatic subjects are
usually defined as patients whose baseline pre-bronchodilation forced expiratory
volume in one second (FEV1) of less than 70-80% predicted improves significantly
in response to beta 2 agonists but by less than 15% following 1-2 weeks of 40 mg
prednisolone daily. Since there is little long term clinical information on these
patients, a one year prospective study was performed to assess whether
glucocorticoid sensitivity may vary over time. METHODS: Nineteen severe asthmatic
subjects were studied and received 40 mg prednisolone daily for seven days.
Prednisolone was given for a further seven days in glucocorticoid insensitive
asthmatics and then stopped. Patients were followed up for one year and the
glucocorticoid test was repeated on five patients in each group six months later.
RESULTS: Eleven patients were classified as glucocorticoid insensitive and eight
as glucocorticoid sensitive on day 7. The demographic characteristics of the
patients were similar in both groups. Four glucocorticoid insensitive patients
became responsive after one further week of prednisolone treatment. Six months
later, four of five glucocorticoid sensitive patients and three of five
previously glucocorticoid insensitive patients were glucocorticoid sensitive.
CONCLUSIONS: Glucocorticoid sensitivity varies over time.
PMID- 10195082
TI - Cellular responses to hypoxia in the pulmonary circulation.
PMID- 10195081
TI - Review of psychosocial stress and asthma: an integrated biopsychosocial approach.
AB - Environmental stressors may impact asthma morbidity through neuroimmunological
mechanisms which are adversely impacted and/or buffered y social networks, social
support, and psychological functioning. In addition, life stress may impact on
health beliefs and behaviours that may affect asthma management. Whereas earlier
psychosomatic models have supported a role for psychological stress in
contributing to variable asthma morbidity among those with existing disease, a
growing appreciation of the interactions between behavioural, neural, endocrine,
and immune processes suggest a role for these psychosocial factors in the genesis
of asthma as well. While a causal link between stress and asthma has not bee
established, this review provides a framework in which we can begin to see links
between these systems that might provide new insights to guide future
explorations. The complexity of these interactions underscore the need for a
multidisciplinary approach which combines the idea that the origin of asthma is
purely psychogenic in nature with the antithetical consideration that the
biological aspects are all important. These distinctions are artificial, and
future research that synthesizes biological, psychological, sociocultural, and
family parameters is urgently needed to further our understanding of the rising
burden of asthma.
PMID- 10195083
TI - Clinical usefulness of high resolution computed tomography in cryptogenic
fibrosing alveolitis.
PMID- 10195084
TI - Diagnosis of pulmonary sequestration by spiral CT angiography.
AB - The diagnosis of pulmonary sequestration traditionally requires arteriography to
identify abnormal systemic vessels feeding the abnormal portion of the lung. Non
invasive imaging techniques have recently been used to replace arteriography.
Conventional computed tomographic (CT) scanning is, however, at a disadvantage
because of its inability to obtain multiplanar images. The combination of slip
ring CT scanning and computerised three-dimensional reconstruction (spiral CT
angiography) can be used to visualise the anatomical detail of a wide range of
vessels within the lung. Four cases of pulmonary sequestration are reported which
were successfully diagnosed using spiral CT angiography. Spiral CT scanning
allows simultaneous imaging of anomalous vessels and lung parenchyma in a single
examination and is particularly useful in the diagnosis and assessment of
pulmonary sequestration.
PMID- 10195085
TI - Interventricular septal shift due to massive pulmonary embolism shown by CT
pulmonary angiography: an old sign revisited.
AB - The computed tomographic (CT) pulmonary angiogram appearances of acute right
ventricular dysfunction due to massive pulmonary embolus in a patient are
described. Abnormal findings comprised right ventricular dilatation,
interventricular septal shift, and compression of the left ventricle. These
changes resolved following thrombolysis. Use of CT pulmonary angiography to
diagnose pulmonary emboli is increasing. Secondary cardiac effects are
established diagnostic features shown by echocardiography. These have not been
previously described but are important to recognise as they may carry important
prognostic and therapeutic implications.
PMID- 10195086
TI - Cardiac risks with beta agonists.
PMID- 10195087
TI - Chlamydia pneumoniae and asthma.
PMID- 10195088
TI - Genetics and tuberculosis.
PMID- 10195089
TI - Chlamydia pneumoniae and asthma.
PMID- 10195090
TI - Non-Hodgkin's lymphoma with CFA.
PMID- 10195091
TI - The clinical management of sarcoidosis. A 50-year experience at the Johns Hopkins
Hospital.
AB - Sarcoidosis is an enigmatic disease with extremely variable manifestations in
pattern, severity and course. Since Longcope and Freiman's descriptive monograph
in 1952 (50) summarizing the clinical findings of the first half of this century,
new dimensions of assessing the disease and treatment have been added. The impact
of corticosteroids is central. The present review extends the studies to the
second half of this century. Earlier diagnosis is facilitated and treatment often
reverses many of the disease manifestations and improves the quality and extent
of life for the patient. The management issues and guidelines outlined in this
paper for both intrathoracic and extrathoracic disease are based on several
longitudinal studies of the sarcoidosis patients summarized here, and 50 years of
clinical experience by the senior author (CJJ) at Johns Hopkins Hospital, a
tertiary referral center with an active Sarcoid Clinic. Case reports are
presented in the appendix. It is clear that corticosteroids are the most
effective therapeutic agent for sarcoidosis, usually with impressive and prompt
response. This represents the dramatic difference in this disease after 1950. No
more specific or effective immunosuppressive or antiinflammatory agents have been
identified. Undesirable side effects are minimal if excessive doses are avoided.
The effectiveness of "steroid-sparing agents" such as methotrexate is uncertain.
Although irreversible tissue damage from the disease may limit the effectiveness
of treatment, benefits of corticosteroids greatly exceed the negative side
effects. Since spontaneous remissions without treatment do occur, a period of
observation of 2 years are more is warranted if the patient is relatively
asymptomatic. Gradual radiographic progression for 2 or more years, even without
major symptoms or reduction in pulmonary function, indicates the need for a trial
of corticosteroid treatment, especially in white patients where symptoms may lag
behind the radiographic changes. Relapses as treatment is withdrawn are frequent,
especially in African-American patients, who tend to have more severe and more
prolonged disease than white patients. A minimum of 1 year of treatment is
recommended unless no improvement is noted after 3 months. Continued low-dose
prednisone at daily doses of 10-15 mg is helpful in preventing relapses and
further progression of disease. Periodic attempts at tapering are justified.
Repeated relapses may indicate the need for life-long treatment. When
irreversible changes are present, especially in the presence of chronic fibrotic
disease, changing goals of treatment to provide optimal supportive care may
represent better management than having unrealistic expectations from increased
corticosteroid dosage or the addition of other potentially toxic
immunosuppressive agents. Many agents related to sarcoidosis require further
research. The most important question facing sarcoid researchers today is
etiology. It is difficult to design specific therapy when the fundamental causes
and disease mechanisms are not established. Rather than being a single disease
with a single cause, it is possible that a number of genetic factors and
environmental or infectious agents may result in an immune response that is
manifested as sarcoidosis. Understanding basic causal mechanisms may help explain
the varied disease manifestations and aid in designing curative treatments. Such
etiologic questions should be explored from both a basic science and an
epidemiologic approach. Therapeutic trials of new drugs such as pentoxyfylline
and possibly thalidomide are needed to address their potential as well as
limitations of steroid therapy. Finally, for patients who have progressed to
organ failure, the problems of sarcoid recurrence in transplanted tissue,
increased allograft rejection, and long-term prognosis of solid organ transplants
have yet to be resolved. (ABSTRACT TRUNCATED)
PMID- 10195093
TI - Invasive aspergillosis in transplant recipients.
PMID- 10195092
TI - Sarcoidosis presenting as a tumorlike muscular lesion. Case report and review of
the literature.
AB - Sarcoid myopathy presenting as a tumorlike lesion is an exceedingly rare
presentation of sarcoidosis. Concurrent extramuscular involvement is common.
Chest radiographs, if abnormal, may suggest the diagnosis. Magnetic resonance
imaging is the preferred study for diagnosis and follow-up of tumorous sarcoid
myopathy. Optimal therapy is not clear. Favorable responses have been cited with
surgery or corticosteroids (alone or in combination). Azathioprine or alternative
immunosuppressive agents (for example, antimalarials or methotrexate) may have a
role in corticosteroid-recalcitrant patients. The role of local radiotherapy is
controversial and should be reserved for severe localized disease refractory to
aggressive medical therapy.
PMID- 10195094
TI - From neurons to thoughts: exploring the new frontier.
PMID- 10195095
TI - Into orbit.
PMID- 10195096
TI - Stress hormones and brain aging: adding injury to insult?
PMID- 10195097
TI - How do you feel? Neurotrophins and mechanotransduction.
PMID- 10195099
TI - Low rates yield big returns.
PMID- 10195098
TI - A sense of direction: going with the flow.
PMID- 10195100
TI - Neurolab launches the decade of the brain into space.
PMID- 10195101
TI - Simple spike activity predicts occurrence of complex spikes in cerebellar
Purkinje cells.
PMID- 10195102
TI - Sex, lies and virtual reality.
PMID- 10195103
TI - Parietal neglect and visual awareness.
AB - The last decade has seen a resurgence of interest in the neural correlates of
conscious vision, with most discussion focused on the 'blindsight' that can
follow damage to primary visual cortex, in the occipital lobe. We suggest that
new insights into the neural basis of visual awareness may be gleaned from a
different neuropsychological phenomenon, namely visual 'neglect' after injury to
regions in the parietal lobe. Neglect provides several revealing contrasts with
occipital blindsight. Here we summarise four key findings. First, unlike the
deficits caused by damage to primary visual cortex, the loss of awareness in
parietal neglect is characteristically not strictly retinotopic. Second, visual
segmentation processes are preserved in neglect, and can influence what will
reach the patient's awareness. Third, extensive unconscious processing takes
place for those stimuli on the neglected side which escape awareness, including
some degree of object identification. Finally, parietal damage affects initial
stages of motor planning as well as perception. These findings are consistent
with recent data on single-cell activity in the monkey brain. They also suggest
why areas in the inferior parietal lobe may play a prominent role in visual
awareness.
PMID- 10195104
TI - Adjacent phosphorylation sites on GABAA receptor beta subunits determine
regulation by cAMP-dependent protein kinase.
AB - Activation of cAMP-dependent protein kinase (PKA) can enhance or reduce the
function of neuronal GABAA receptors, the major sites of fast synaptic inhibition
in the brain. This differential regulation depends on PKA-induced phosphorylation
of adjacent conserved sites in the receptor beta subunits. Phosphorylation of
beta 3 subunit-containing receptors at S408 and S409 enhanced the GABA-activated
response, whereas selectively mutating S408 to alanine converted the potentiation
into an inhibition, comparable to that of beta 1 subunits, which are
phosphorylated solely on S409. These distinct modes of regulation were
interconvertible between beta 1 and beta 3 subunits and depended upon the
presence of S408 in either subunit. In contrast, beta 2 subunit-containing
receptors were not phosphorylated or affected by PKA. Differential regulation by
PKA of postsynaptic GABAA receptors containing different beta subunits may have
profound effects on neuronal excitability.
PMID- 10195105
TI - Two sites of action for synapsin domain E in regulating neurotransmitter release.
AB - Synapsins, a family of synaptic vesicle proteins, have been shown to regulate
neurotransmitter release; the mechanism(s) by which they act are not fully
understood. Here we have studied the role of domain E of synapsins in
neurotransmitter release at the squid giant synapse. Two squid synapsin isoforms
were cloned and found to contain a carboxy (C)-terminal domain homologous to
domain E of the vertebrate a-type synapsin isoforms. Presynaptic injection of a
peptide fragment of domain E greatly reduced the number of synaptic vesicles in
the periphery of the active zone, and increased the rate and extent of synaptic
depression, suggesting that domain E is essential for synapsins to regulate a
reserve pool of synaptic vesicles. Domain E peptide had no effect on the number
of docked synaptic vesicles, yet reversibly inhibited and slowed the kinetics of
neurotransmitter release, indicating a second role for synapsins that is more
intimately associated with the release process itself. Thus, synapsin domain E is
involved in at least two distinct reactions that are crucial for exocytosis in
presynaptic terminals.
PMID- 10195106
TI - The metabolic cost of neural information.
AB - We derive experimentally based estimates of the energy used by neural mechanisms
to code known quantities of information. Biophysical measurements from cells in
the blowfly retina yield estimates of the ATP required to generate graded
(analog) electrical signals that transmit known amounts of information. Energy
consumption is several orders of magnitude greater than the thermodynamic
minimum. It costs 10(4) ATP molecules to transmit a bit at a chemical synapse,
and 10(6)-10(7) ATP for graded signals in an interneuron or a photoreceptor, or
for spike coding. Therefore, in noise-limited signaling systems, a weak pathway
of low capacity transmits information more economically, which promotes the
distribution of information among multiple pathways.
PMID- 10195107
TI - A role for BDNF in mechanosensation.
AB - Brain-derived neurotrophic factor (BDNF) is a survival factor for certain sensory
neurons during development. Using electrophysiology in BDNF-deficient mice, we
show here that slowly adapting mechanoreceptors (SAM), but not other types of
cutaneous afferents, require BDNF in postnatal life for normal
mechanotransduction. Neurons lacking BDNF did not die, but instead showed a
profound and specific reduction in their mechanical sensitivity, which was
quantitatively the same in BDNF -/- and BDNF +/- animals. Postnatal treatment of
BDNF +/- mice with recombinant BDNF completely rescued the mechanosensitivity
deficit. Therefore BDNF is important for regulating SAM mechanosensitivity,
independent of any survival-promoting function.
PMID- 10195108
TI - Tissue plasminogen activator mediates reverse occlusion plasticity in visual
cortex.
AB - Preventing visual input to one eye (monocular deprivation) in early postnatal
development reduces cortical responses to stimulation of the deprived eye, with a
significant loss of thalamocortical connections. These effects are reversible by
opening the deprived eye and closing the previously open eye (reverse occlusion).
We show that intracortical blockade of tissue plasminogen activator or plasmin
selectively prevents recovery of cortical function and thalamic neuron size
during reverse occlusion, without affecting the monocular deprivation response.
Therefore, a proteolytic cascade consisting of plasmin generated by tissue
plasminogen activator may selectively mediate reverse-occlusion-induced cortical
plasticity, perhaps via structural remodeling of axons.
PMID- 10195109
TI - Corticofugal modulation of the midbrain frequency map in the bat auditory system.
AB - The auditory system, like the visual and somatosensory systems, contains
topographic maps in its central neural pathways. These maps can be modified by
sensory deprivation, injury and experience in both young and adult animals. Such
plasticity has been explained by changes in the divergent and convergent
projections of the ascending sensory system. Another possibility, however, is
that plasticity may be mediated by descending corticofugal connections. We have
investigated the role of descending connections from the cortex to the inferior
colliculus of the big brown bat. Electrical stimulation of the auditory cortex
causes a downward shift in the preferred frequencies of collicular neurons toward
that of the stimulated cortical neurons. This results in a change in the
frequency map within the colliculus. Moreover, similar changes can be induced by
repeated bursts of sound at moderate intensities. Thus, one role of the mammalian
corticofugal system may be to modify subcortical sensory maps in response to
sensory experience.
PMID- 10195110
TI - Electrical microstimulation of cortical area MST biases heading perception in
monkeys.
AB - As we move through the environment, the pattern of visual motion on the retina
provides rich information about our movement through the scene. Human subjects
can use this information, often termed "optic flow", to accurately estimate their
direction of self movement (heading) from relatively sparse displays.
Physiological observations on the motion-sensitive areas of monkey visual cortex
suggest that the medial superior temporal area (MST) is well suited for the
analysis of optic flow information. To test whether MST is involved in extracting
heading from optic flow, we perturbed its activity in monkeys trained on a
heading discrimination task. Electrical microstimulation of MST frequently biased
the monkeys' decisions about their heading, and these induced biases were often
quite large. This result suggests that MST has a direct role in the perception of
heading from optic flow.
PMID- 10195111
TI - Long-term reorganization of human motor cortex driven by short-term sensory
stimulation.
AB - Removal of sensory input can induce changes in cortical motor representation that
reverse when sensation is restored. Here we ask whether manipulation of sensory
input can induce long-term reorganization in human motor cortex that outlasts the
initial conditioning. We report that for at least 30 minutes after pharyngeal
stimulation, motor cortex excitability and area of representation for the pharynx
increased, while esophagus representation decreased, without parallel changes in
the excitability of brainstem-mediated reflexes. Therefore increased sensory
input can drive long-term cross-system changes in motor areas of the cerebral
cortex, which suggests that sensory stimulation might rehabilitate dysphagia, a
frequent consequence of cerebral injury.
PMID- 10195112
TI - Cortisol levels during human aging predict hippocampal atrophy and memory
deficits.
AB - Elevated glucocorticoid levels produce hippocampal dysfunction and correlate with
individual deficits in spatial learning in aged rats. Previously we related
persistent cortisol increases to memory impairments in elderly humans studied
over five years. Here we demonstrate that aged humans with significant prolonged
cortisol elevations showed reduced hippocampal volume and deficits in hippocampus
dependent memory tasks compared to normal-cortisol controls. Moreover, the degree
of hippocampal atrophy correlated strongly with both the degree of cortisol
elevation over time and current basal cortisol levels. Therefore, basal cortisol
elevation may cause hippocampal damage and impair hippocampus-dependent learning
and memory in humans.
PMID- 10195113
TI - Right parietal cortex is involved in the perception of sound movement in humans.
AB - Changes in the delay (phase) and amplitude of sound at the ears are cues for the
analysis of sound movement. The detection of these cues depends on the
convergence of the inputs to each ear, a process that first occurs in the
brainstem. The conscious perception of these cues is likely to involve higher
centers. Using novel stimuli that produce different perceptions of movement in
the presence of identical phase and amplitude modulation components, we have
demonstrated human brain areas that are active specifically during the perception
of sound movement. Both functional magnetic resonance imaging (fMRI) and positron
emission tomography (PET) demonstrated the involvement of the right parietal
cortex in sound movement perception with these stimuli.
PMID- 10195114
TI - Transient activation of inferior prefrontal cortex during cognitive set shifting.
AB - The Wisconsin Card Sorting Test, which probes the ability to shift attention from
one category of stimulus attributes to another (shifting cognitive sets), is the
most common paradigm used to detect human frontal lobe pathology. However, the
exact relationship of this card test to prefrontal function and the precise
anatomical localization of the cognitive shifts involved are controversial. By
isolating shift-related signals using the temporal resolution of functional
magnetic resonance imaging, we reproducibly found transient activation of the
posterior part of the bilateral inferior frontal sulci. This activation was
larger as the number of dimensions (relevant stimulus attributes that had to be
recognized) were increased. These results suggest that the inferior frontal areas
play an essential role in the flexible shifting of cognitive sets.
PMID- 10195115
TI - New compensations for spinal injury.
PMID- 10195116
TI - Containing plasticity: neurite inhibitory factors of myelin.
PMID- 10195117
TI - Long-term depression with a flash.
PMID- 10195119
TI - Shining light on spiny matters.
PMID- 10195118
TI - Cocaine abuse: hard knocks for the dopamine hypothesis?
PMID- 10195120
TI - Visual cortex: pushing the envelope.
PMID- 10195121
TI - Visual psychophysics: synchrony in motion.
PMID- 10195122
TI - Persyn, a member of the synuclein family, influences neurofilament network
integrity.
PMID- 10195123
TI - Leptin affects food intake via CRF-receptor-mediated pathways.
PMID- 10195124
TI - Arachidonic acid elicits a substrate-gated proton current associated with the
glutamate transporter EAAT4.
AB - Arachidonic acid modulates both electrical and biochemical properties of membrane
proteins involved in cellular signaling. In Xenopus laevis oocytes expressing the
excitatory amino acid transporter EAAT4, physiologically relevant concentrations
of arachidonic acid increase the amplitude of the substrate-activated current by
roughly twofold at -60 mV. This stimulation is not attributable to the modulation
of either substrate/ion cotransport or the ligand-gated chloride current, the
major conductance associated with this carrier. Ion-substitution experiments
reveal that arachidonic acid stimulates a proton-selective conductance. The
effect does not require metabolism of arachidonic acid and is not blocked by
inhibitors of endogenous oocyte ion-exchangers. This proton conductance expands
the complex repertoire of the ligand-gated channel properties associated with
EAAT4.
PMID- 10195125
TI - NMDA receptors amplify calcium influx into dendritic spines during associative
pre- and postsynaptic activation.
AB - Long-term potentiation (LTP) of synaptic strength can be induced by synchronous
pre- and postsynaptic activation, and a rise in postsynaptic calcium is essential
for induction of LTP. Calcium can enter through both voltage-dependent Ca2+
channels and NMDA-type glutamate receptors, but the relative contributions of
these pathways is not known. We have examined this issue in layer V cortical
pyramidal neurons, using focal flash photolysis of caged glutamate to mimic
synaptic input and two-photon, laser-scanning microscopy to measure calcium
levels in dendritic spines. Most of the calcium entry in response to glutamate
alone was via voltage-dependent Ca2+ channels, and NMDA receptors accounted for
less than 20% of total Ca2+ entry. When glutamate was paired with postsynaptic
action potentials, however, the NMDA-receptor-dependent component was selectively
amplified. The same is likely to occur during paired physiological pre- and
postsynaptic activation, providing a mechanism for the input specificity and
Hebbian behavior of LTP.
PMID- 10195126
TI - Focal photolysis of caged glutamate produces long-term depression of hippocampal
glutamate receptors.
AB - Separating contributions of pre- and postsynaptic factors to the maintenance of
long-term potentiation (LTP) and long-term depression (LTD) has been confounded
by their experimental interdependence. To isolate the postsynaptic contribution,
glutamate-receptor-mediated currents were elicited by localized photolysis of
caged glutamate in small spots along the dendrites of CA1 hippocampal pyramidal
cells. With synaptic transmission blocked, pairing depolarization of pyramidal
cells with repeated photolysis of caged glutamate at one site markedly and
persistently depressed subsequent responses to glutamate; responses at a second,
unpaired site were unchanged. Like synaptically induced LTD at the CA3-CA1
synapse, this depression was site specific, NMDA-receptor dependent and blocked
by protein-phosphatase inhibitors. Thus, robust, persistent alterations of
postsynaptic glutamate receptor efficacy can occur without presynaptic
neurotransmitter release.
PMID- 10195127
TI - Neurite growth inhibitors restrict plasticity and functional recovery following
corticospinal tract lesions.
AB - Anatomical plasticity and functional recovery after lesions of the rodent
corticospinal tract (CST) decrease postnatally in parallel with myelin formation.
Myelin-associated neurite growth inhibitory proteins prevent regenerative fiber
growth, but whether they also prevent reactive sprouting of unlesioned fibers is
less clear. Here we show that after unilateral CST lesion in the adult rat
brainstem, both intact and lesioned tracts show topographically appropriate
sprouting after treatment with a monoclonal antibody that neutralizes these
inhibitory proteins. Antibody-treated animals showed full recovery in motor and
sensory tests, whereas untreated lesioned rats exhibited persistent severe
deficits. Neutralization of myelin-associated neurite growth inhibitors thus
restores in adults the structural plasticity and functional recovery normally
found only at perinatal ages.
PMID- 10195128
TI - Cocaine self-administration in dopamine-transporter knockout mice.
AB - The plasma membrane dopamine transporter (DAT) is responsible for clearing
dopamine from the synapse. Cocaine blockade of DAT leads to increased
extracellular dopamine, an effect widely considered to be the primary cause of
the reinforcing and addictive properties of cocaine. In this study we tested
whether these properties are limited to the dopaminergic system in mice lacking
DAT. In the absence of DAT, these mice exhibit high levels of extracellular
dopamine, but paradoxically still self-administer cocaine. Mapping of the sites
of cocaine binding and neuronal activation suggests an involvement of
serotonergic brain regions in this response. These results demonstrate that the
interaction of cocaine with targets other than DAT, possibly the serotonin
transporter, can initiate and sustain cocaine self-administration in these mice.
PMID- 10195129
TI - Receptor organ damage causes loss of cortical surround inhibition without
topographic map plasticity.
AB - Following restricted peripheral damage, reorganization of adult sensory or motor
cortex is believed to depend on loss of surround inhibition, which unmasks latent
inputs to the deprived cortex. Here I demonstrate that limited damage to auditory
receptors causes loss of functional surround inhibition in the cortex, unmasking
of latent inputs and significantly altered neural coding. However, these changes
do not lead to plasticity of the cortical map, defined by the most sensitive
input from the receptor surface to each cortical location. Thus, in sensory
cortex, loss of surround inhibition as a consequence of receptor organ damage
does not necessarily result in cortical map plasticity.
PMID- 10195130
TI - Neuronal correlates of visibility and invisibility in the primate visual system.
AB - A brief visual target stimulus may be rendered invisible if it is immediately
preceded or followed by another stimulus. This class of illusions, known as
visual masking, may allow insights into the neural mechanisms that underlie
visual perception. We have therefore explored the temporal characteristics of
masking illusions in humans, and compared them with corresponding neuronal
responses in the primary visual cortex of awake and anesthetized monkeys.
Stimulus parameters that in humans produce forward masking (in which the mask
precedes the target) suppress the transient on-response to the target in monkey
visual cortex. Those that produce backward masking (in which the mask comes after
the target) inhibit the transient after-discharge, the excitatory response that
occurs just after the disappearance of the target. These results suggest that,
for targets that can be masked (those of short duration), the transient neuronal
responses associated with onset and turning off of the target may be important in
its visibility.
PMID- 10195131
TI - A cortical locus for the processing of contrast-defined contours.
AB - Object boundaries in the natural environment are often defined by changes in
luminance; in other cases, however, there may be no difference in average
luminance across the boundary, which is instead defined by more subtle 'second
order' cues, such as changes in the contrast of a fine-grained texture. The
detection of luminance boundaries may be readily explained in terms of visual
cortical neurons, which compute the linear sum of the excitatory and inhibitory
inputs to different parts of their receptive field. The detection of second-order
stimuli is less well understood, but is thought to involve a separate nonlinear
processing stream, in which boundary detectors would receive inputs from many
smaller subunits. To address this, we have examined the properties of cortical
neurons which respond to both first- and second-order stimuli. We show that the
inputs to these neurons are also oriented, but with no fixed orientational
relationship to the neurons they subserve. Our results suggest a flexible
mechanism by which the visual cortex can detect object boundaries regardless of
whether they are defined by luminance or texture.
PMID- 10195132
TI - Orbitofrontal cortex and basolateral amygdala encode expected outcomes during
learning.
AB - Reciprocal connections between the orbitofrontal cortex and the basolateral
nucleus of the amygdala may provide a critical circuit for the learning that
underlies goal-directed behavior. We examined neural activity in rat
orbitofrontal cortex and basolateral amygdala during instrumental learning in an
olfactory discrimination task. Neurons in both regions fired selectively during
the anticipation of rewarding or aversive outcomes. This selective activity
emerged early in training, before the rats had learned reliably to avoid the
aversive outcome. The results support the concept that the basolateral amygdala
and orbitofrontal cortex cooperate to encode information that may be used to
guide goal-directed behavior.
PMID- 10195133
TI - Visual features that vary together over time group together over space.
AB - The visual system perceives objects as coherent even when some parts are hidden
or discontinuous. How this representation is constructed from local features of
many nearby objects is termed the 'binding problem.' Here we manipulate contrast
in several drifting gratings that can be perceived as either independent objects
or parts of a single object. Contrast modulations that are correlated in time
enhance perceptual coherence, whereas uncorrelated modulations impair coherence.
Presumably, correlated contrast modulations produce correlated responses in
cortical neurons. Therefore, our results are consistent with the hypothesis that
temporal correlation of neural activity is important for feature binding.
PMID- 10195134
TI - Visual search for motion-in-depth: stereomotion does not 'pop out' from disparity
noise.
AB - In a visual search task, targets defined by motion or binocular disparity stand
out effortlessly from stationary distractors ('pop-out'), suggesting that target
and distractors are processed by different neural mechanisms. We used pop-out to
explore whether motion directly toward or away from the observer (z-motion) is
detected using binocular motion cues. A target moving laterally (x-motion) popped
out amid stationary distractors with binocular disparity, but z-motion did not
pop out. However, a small x-motion added to the target's z-motion caused it to
pop out. We therefore suggest that the visual system may not be specifically
sensitive to binocular motion differences.
PMID- 10195135
TI - Making sense of channel diversity.
PMID- 10195136
TI - With color in mind.
PMID- 10195137
TI - Zinc, Src and NMDA receptors--a transmembrane connection.
PMID- 10195138
TI - Probing a complex question: when are SNARE proteins ensnared?
PMID- 10195139
TI - Getting a line on pain: is it mediated by dedicated pathways?
PMID- 10195140
TI - Cortical control of the thalamus: top-down processing and plasticity.
PMID- 10195141
TI - Where is the sun?
PMID- 10195142
TI - Tyrosine kinase potentiates NMDA receptor currents by reducing tonic zinc
inhibition.
AB - Activation of the tyrosine kinase Src potentiates NMDA-receptor currents, which
is thought to be necessary for induction of hippocampal long-term potentiation.
Although the carboxy(C)-terminal domain of the NR2A subunit contains potential
tyrosine phosphorylation sites, the mechanisms by which Src modulates synaptic
plasticity and NMDA receptor currents is not fully understood. Here we present
evidence from NR1 mutants and splice variants that Src potentiates NMDA-receptor
currents by reducing the tonic inhibition of receptors composed of NR1 and NR2A
subunits by extracellular zinc. Using site-directed mutagenesis, we have
identified three C-terminal tyrosine residues of NR2A that are required for Src's
modulation of the zinc sensitivity of NMDA receptors. Our data link two
modulatory sites of NMDA receptors that were previously thought to be
independent.
PMID- 10195143
TI - Multiple kinetic components of exocytosis distinguished by neurotoxin
sensitivity.
AB - The secretion of synaptic and other vesicles is a complex process involving
multiple steps. Many molecular components of the secretory apparatus have been
identified, but how they relate to the different stages of vesicle release is not
clear. We examined this issue in adrenal chromaffin cells, where capacitance
measurements and amperometry allow us to measure vesicle fusion and hormone
release simultaneously. Using flash photolysis of caged intracellular calcium to
induce exocytosis, we observed three distinct kinetic components to vesicle
fusion, of which only two are related to catecholamine release. Intracellular
dialysis with botulinum neurotoxin E, D or C1 or tetanus-toxin light chains
abolishes the catecholamine-related components, but leaves the third component
untouched. Botulinum neurotoxin A, which removes nine amino acids from the
carboxy(C)-terminal end of SNAP-25, does not eliminate catecholamine release
completely, but slows down both catecholamine-related components. Thus we assign
a dual role to SNAP-25 and suggest that its nine C-terminal amino acids are
directly involved in coupling the calcium sensor to the final step in exocytosis.
PMID- 10195144
TI - Presynaptic modulation of CA3 network activity.
AB - The simultaneous discharge of hippocampal CA3 pyramidal cells is a widely studied
in vitro model of physiological and pathological network synchronization. This
network is rapidly activated because of extensive positive feedback mediated by
recurrent axon collaterals. Here we show that population-burst duration is
limited by depletion of the releasable glutamate pool at these recurrent
synapses. Postsynaptic inhibitory conductances further limit burst duration but
are not necessary for burst termination. The interval between bursts in vitro
depends on the rate of replenishment of releasable glutamate vesicles and the
probability of release of those vesicles at recurrent synapses. Therefore
presynaptic factors controlling glutamate release at recurrent synapses regulate
the probability and duration of synchronous discharges of the CA3 network.
PMID- 10195145
TI - Input synchrony and the irregular firing of cortical neurons.
AB - Cortical neurons in the waking brain fire highly irregular, seemingly random,
spike trains in response to constant sensory stimulation, whereas in vitro they
fire regularly in response to constant current injection. To test whether, as has
been suggested, this high in vivo variability could be due to the postsynaptic
currents generated by independent synaptic inputs, we injected synthetic synaptic
current into neocortical neurons in brain slices. We report that independent
inputs cannot account for this high variability, but this variability can be
explained by a simple alternative model of the synaptic drive in which inputs
arrive synchronously. Our results suggest that synchrony may be important in the
neural code by providing a means for encoding signals with high temporal fidelity
over a population of neurons.
PMID- 10195146
TI - Nociceptive and thermoreceptive lamina I neurons are anatomically distinct.
AB - Pain and temperature stimuli activate neurons of lamina I within the dorsal horn
of the spinal cord, and although these neurons can be classified into three basic
morphological types and three major physiological classes, earlier studies did
not establish a structure/function correlation between their morphology and their
physiological responses. We recorded and intracellularly labeled 38 cat lamina I
neurons. All 12 fusiform cells were nociceptive-specific, responsive only to
pinch and/or heat. All 11 pyramidal cells were thermoreceptive-specific,
responsive only to innocuous cooling. Of ten multipolar cells, six were
polymodal, responsive to heat, pinch and cold, and four were nociceptive
specific. Five unclassified cells had features consistent with this pattern.
These results support the view that central pain and temperature pathways contain
anatomically discrete sets of modality-selective neurons.
PMID- 10195147
TI - Cortically induced thalamic plasticity in the primate somatosensory system.
AB - The influence of cortical feedback on receptive field organization in the
thalamus was assessed in the primate somatosensory system. Chronic and acute
suppression of neuronal activity in primary somatosensory cortex resulted in a
striking enlargement of receptive fields in the ventroposterior thalamus. This
finding demonstrates a dramatic 'top-down' influence of cortex on receptive field
size in the somatosensory thalamus. In addition, this result has important
implications for studies of adult neuronal plasticity because it indicates that
changes in 'higher-order' areas of the brain can trigger extensive changes in the
receptive field characteristics of neurons located earlier in the processing
pathway.
PMID- 10195148
TI - Strengthening of horizontal cortical connections following skill learning.
AB - Learning a new motor skill requires an alteration in the spatiotemporal pattern
of muscle activation. Motor areas of cerebral neocortex are thought to be
involved in this type of learning, possibly by functional reorganization of
cortical connections. Here we show that skill learning is accompanied by changes
in the strength of connections within adult rat primary motor cortex (M1). Rats
were trained for three or five days in a skilled reaching task with one forelimb,
after which slices of motor cortex were examined to determine the effect of
training on the strength of horizontal intracortical connections in layer II/III.
The amplitude of field potentials in the forelimb region contralateral to the
trained limb was significantly increased relative to the opposite 'untrained'
hemisphere. No differences were seen in the hindlimb region. Moreover, the amount
of long-term potentiation (LTP) that could be induced in trained M1 was less than
in controls, suggesting that the effect of training was at least partly due to
LTP-like mechanisms. These data represent the first direct evidence that
plasticity of intracortical connections is associated with learning a new motor
skill.
PMID- 10195149
TI - Retinotopy and color sensitivity in human visual cortical area V8.
AB - Prior studies suggest the presence of a color-selective area in the inferior
occipital-temporal region of human visual cortex. It has been proposed that this
human area is homologous to macaque area V4, which is arguably color selective,
but this has never been tested directly. To test this model, we compared the
location of the human color-selective region to the retinotopic area boundaries
in the same subjects, using functional magnetic resonance imaging (fMRI),
cortical flattening and retinotopic mapping techniques. The human color-selective
region did not match the location of area V4 (neither its dorsal nor ventral
subdivisions), as extrapolated from macaque maps. Instead this region coincides
with a new retinotopic area that we call 'V8', which includes a distinct
representation of the fovea and both upper and lower visual fields. We also
tested the response to stimuli that produce color afterimages and found that
these stimuli, like real colors, caused preferential activation of V8 but not V4.
PMID- 10195150
TI - Complete sparing of high-contrast color input to motion perception in cortical
color blindness.
AB - It is widely held that color and motion are processed by separate parallel
pathways in the visual system, but this view is difficult to reconcile with the
fact that motion can be detected in equiluminant stimuli that are defined by
color alone. To examine the relationship between color and motion, we tested
three patients who had lost their color vision following cortical damage (central
achromatopsia). Despite their profound loss in the subjective experience of color
and their inability to detect the motion of faint colors, all three subjects
showed surprisingly strong responses to high-contrast, moving color stimuli-
equal in all respects to the performance of subjects with normal color vision.
The pathway from opponent-color detectors in the retina to the motion analysis
areas must therefore be independent of the damaged color centers in the
occipitotemporal area. It is probably also independent of the motion analysis
area MT/V5, because the contribution of color to motion detection in these
patients is much stronger than the color response of monkey area MT.
PMID- 10195151
TI - The effects of frontal eye field and dorsomedial frontal cortex lesions on
visually guided eye movements.
AB - In the frontal lobe of primates, two areas play a role in visually guided eye
movements: the frontal eye fields (FEF) and the medial eye fields (MEF) in
dorsomedial frontal cortex. Previously, FEF lesions have revealed only mild
deficits in saccadic eye movements that recovered rapidly. Deficits in eye
movements after MEF ablation have not been shown. We report the effects of
ablating these areas singly or in combination, using tests in which animals were
trained to make saccadic eye movements to paired or multiple targets presented at
various temporal asynchronies. FEF lesions produced large and long-lasting
deficits on both tasks. Sequences of eye movements made to successively presented
targets were also impaired. Much smaller deficits were observed after MEF
lesions. Our findings indicate a major, long-lasting loss in temporal ordering
and processing speed for visually guided saccadic eye movement generation after
FEF lesions and a significant but smaller and shorter-lasting loss after MEF
lesions.
PMID- 10195152
TI - Top-down influences on stereoscopic depth-perception.
AB - The interaction between depth perception and object recognition has important
implications for the nature of mental object representations and models of
hierarchical organization of visual processing. It is often believed that the
computation of depth influences subsequent high-level object recognition
processes, and that depth processing is an early vision task that is largely
immune to 'top-down' object-specific influences, such as object recognition. Here
we present experimental evidence that challenges both these assumptions in the
specific context of stereoscopic depth-perception. We have found that observers'
recognition of familiar dynamic three-dimensional (3D) objects is unaffected even
when the objects' depth structure is scrambled, as long as their two-dimensional
(2D) projections are unchanged. Furthermore, the observers seem perceptually
unaware of the depth anomalies introduced by scrambling. We attribute the latter
result to a top-down recognition-based influence whereby expectations about a
familiar object's 3D structure override the true stereoscopic information.
PMID- 10195153
TI - Speaking of twins.
PMID- 10195154
TI - Collision-avoidance: nature's many solutions.
PMID- 10195155
TI - Neurogenic control of the cerebral microcirculation: is dopamine minding the
store?
PMID- 10195156
TI - The missing link: a failure of fronto-hippocampal integration in schizophrenia.
PMID- 10195157
TI - Coexpression of Agrp and NPY in fasting-activated hypothalamic neurons.
PMID- 10195158
TI - A role for NMDA-receptor channels in working memory.
PMID- 10195159
TI - Three-dimensional object recognition is viewpoint dependent.
PMID- 10195160
TI - Target-cell-specific facilitation and depression in neocortical circuits.
AB - In neocortical circuits, repetitively active neurons evoke unitary postsynaptic
potentials (PSPs) whose peak amplitudes either increase (facilitate) or decrease
(depress) progressively. To examine the basis for these different synaptic
responses, we made simultaneous recordings from three classes of neurons in
cortical layer 2/3. We induced repetitive action potentials in pyramidal cells
and recorded the evoked unitary excitatory (E)PSPs in two classes of GABAergic
neurons. We observed facilitation of EPSPs in bitufted GABAergic interneurons,
many of which expressed somatostatin immunoreactivity. EPSPs recorded from
multipolar interneurons, however, showed depression. Some of these neurons were
immunopositive for parvalbumin. Unitary inhibitory (I)PSPs evoked by repetitive
stimulation of a bitufted neuron also showed a less pronounced but significant
difference between the two target neurons. Facilitation and depression involve
presynaptic mechanisms, and because a single neuron can express both behaviors
simultaneously, we infer that local differences in the molecular structure of
presynaptic nerve terminals are induced by retrograde signals from different
classes of target neurons. Because bitufted and multipolar neurons both formed
reciprocal inhibitory connections with pyramidal cells, the results imply that
the balance of activation between two recurrent inhibitory pathways in the
neocortex depends on the frequency of action potentials in pyramidal cells.
PMID- 10195161
TI - Dopaminergic regulation of cerebral cortical microcirculation.
AB - Functional variations in cerebral cortical activity are accompanied by local
changes in blood flow, but the mechanisms underlying this physiological coupling
are not well understood. Here we report that dopamine, a neurotransmitter
normally associated with neuromodulatory actions, may directly affect local
cortical blood flow. Using light and electron-microscopic immunocytochemistry, we
show that dopaminergic axons innervate the intraparenchymal microvessels. We also
provide evidence in an in vitro slice preparation that dopamine produces
vasomotor responses in the cortical vasculature. These anatomical and
physiological observations reveal a previously unknown source of regulation of
the microvasculature by dopamine. The findings may be relevant to the mechanisms
underlying changes in blood flow observed in circulatory and neuropsychiatric
disorders.
PMID- 10195162
TI - Transplantation of expanded mesencephalic precursors leads to recovery in
parkinsonian rats.
AB - In vitro expansion of central nervous system (CNS) precursors might overcome the
limited availability of dopaminergic neurons in transplantation for Parkinson's
disease, but generating dopaminergic neurons from in vitro dividing precursors
has proven difficult. Here a three-dimensional cell differentiation system was
used to convert precursor cells derived from E12 rat ventral mesencephalon into
dopaminergic neurons. We demonstrate that CNS precursor cell populations expanded
in vitro can efficiently differentiate into dopaminergic neurons, survive
intrastriatal transplantation and induce functional recovery in hemiparkinsonian
rats. The numerical expansion of primary CNS precursor cells is a new approach
that could improve both the ethical and the technical outlook for the use of
human fetal tissue in clinical transplantation.
PMID- 10195163
TI - Computation of different optical variables of looming objects in pigeon nucleus
rotundus neurons.
AB - Three types of looming-selective neurons have been found in the nucleus rotundus
of pigeons, each computing a different optical variable related to image
expansion of objects approaching on a direct collision course with the bird. None
of these neurons respond to simulated approach toward stationary objects. A
detailed analysis of these neurons' firing pattern to approaching objects of
different sizes and velocities shows that one group of neurons signals relative
rate of expansion tau (tau), a second group signals absolute rate of expansion
rho (rho), and a third group signals yet another optical variable eta (eta). The
rho parameter is required for the computation of both tau and eta, whose
respective ecological functions probably provide precise 'time-to-collision'
information and 'early warning' detection for large approaching objects.
PMID- 10195164
TI - Dopamine neurons report an error in the temporal prediction of reward during
learning.
AB - Many behaviors are affected by rewards, undergoing long-term changes when rewards
are different than predicted but remaining unchanged when rewards occur exactly
as predicted. The discrepancy between reward occurrence and reward prediction is
termed an 'error in reward prediction'. Dopamine neurons in the substantia nigra
and the ventral tegmental area are believed to be involved in reward-dependent
behaviors. Consistent with this role, they are activated by rewards, and because
they are activated more strongly by unpredicted than by predicted rewards they
may play a role in learning. The present study investigated whether monkey
dopamine neurons code an error in reward prediction during the course of
learning. Dopamine neuron responses reflected the changes in reward prediction
during individual learning episodes; dopamine neurons were activated by rewards
during early trials, when errors were frequent and rewards unpredictable, but
activation was progressively reduced as performance was consolidated and rewards
became more predictable. These neurons were also activated when rewards occurred
at unpredicted times and were depressed when rewards were omitted at the
predicted times. Thus, dopamine neurons code errors in the prediction of both the
occurrence and the time of rewards. In this respect, their responses resemble the
teaching signals that have been employed in particularly efficient computational
learning models.
PMID- 10195165
TI - Inter-trial neuronal activity in inferior temporal cortex: a putative vehicle to
generate long-term visual associations.
AB - When monkeys perform a delayed match-to-sample task, some neurons in the anterior
inferotemporal cortex show sustained activity following the presentation of
specific visual stimuli, typically only those that are shown repeatedly. When
sample stimuli are shown in a fixed temporal order, the few images that evoke
delay activity in a given neuron are often neighboring stimuli in the sequence,
suggesting that this delay activity may be the neural correlate of associative
long-term memory. Here we report that stimulus-selective sustained activity is
also evident following the presentation of the test stimulus in the same task. We
use a neural network model to demonstrate that persistent stimulus-selective
activity across the intertrial interval can lead to similar mnemonic
representations (distributions of delay activity across the neural population)
for neighboring visual stimuli. Thus, inferotemporal cortex may contain neural
machinery for generating long-term stimulus-stimulus associations.
PMID- 10195166
TI - Impaired recruitment of the hippocampus during conscious recollection in
schizophrenia.
AB - Poor attention and impaired memory are enduring and core features of
schizophrenia. These impairments have been attributed either to global cortical
dysfunction or to perturbations of specific components associated with the
dorsolateral prefrontal cortex (DLPFC), hippocampus and cerebellum. Here, we used
positron emission tomography (PET) to dissociate activations in DLPFC and
hippocampus during verbal episodic memory retrieval. We found reduced hippocampal
activation during conscious recollection of studied words, but robust activation
of the DLPFC during the effort to retrieve poorly encoded material in
schizophrenic patients. This finding provides the first evidence of hippocampal
dysfunction during episodic memory retrieval in schizophrenia.
PMID- 10195167
TI - Genetic influence on language delay in two-year-old children.
AB - Previous work suggests that most clinically significant language difficulties in
children do not result from acquired brain lesions or adverse environmental
experiences but from genetic factors that presumably influence early brain
development. We conducted the first twin study of language delay to evaluate
whether genetic and environmental factors at the lower extreme of delayed
language are different from those operating in the normal range. Vocabulary at
age two was assessed for more than 3000 pairs of twins. Group differences
heritability for the lowest 5% of subjects was estimated as 73% in model-fitting
analyses, significantly greater than the individual differences heritability for
the entire sample (25%). This supports the view of early language delay as a
distinct disorder. Shared environment was only a quarter as important for the
language-delayed sample (18%) as for the entire sample (69%).
PMID- 10195168
TI - Probing the brain with DNA chips.
PMID- 10195169
TI - Silent synapses: I can't hear you! Could you please speak aloud?
PMID- 10195170
TI - A thorny question: how does activity maintain dendritic spines?
PMID- 10195171
TI - Seeing smells: imaging olfactory learning in bees.
PMID- 10195172
TI - Predicting the visual world: silence is golden.
PMID- 10195173
TI - Orbitofrontal cortex is activated during breaches of expectation in tasks of
visual attention.
PMID- 10195174
TI - Protein phosphatase 1 modulation of neostriatal AMPA channels: regulation by
DARPP-32 and spinophilin.
AB - Modulation of AMPA-type glutamate channels is important for synaptic plasticity.
Here we provide physiological evidence that the activity of AMPA channels is
regulated by protein phosphatase 1 (PP-1) in neostriatal neurons and identify two
distinct molecular mechanisms of this regulation. One mechanism involves control
of PP-1 catalytic activity by DARPP-32, a dopamine- and cAMP-regulated
phosphoprotein highly enriched in neostriatum. The other involves binding of PP-1
to spinophilin, a protein that colocalizes PP-1 with AMPA receptors in
postsynaptic densities. The results suggest that regulation of anchored PP-1 is
important for AMPA-receptor-mediated synaptic transmission and plasticity.
PMID- 10195175
TI - Cyclic GMP pathway is critical for inducing long-term sensitization of
nociceptive sensory neurons.
AB - Noxious stimulation can trigger persistent sensitization of somatosensory systems
that involves memory-like mechanisms. Here we report that noxious stimulation of
the mollusc Aplysia produces transcription-dependent, long-term hyperexcitability
(LTH) of nociceptive sensory neurons that requires a nitric oxide (NO)-cyclic GMP
protein kinase G (PKG) pathway. Injection of cGMP induced LTH, whereas
antagonists of the NO-cGMP-PKG pathway prevented pinch-induced LTH. Co-injection
of calcium/cAMP-responsive-element (CRE) blocked both pinch-induced LTH and cAMP
induced LTH, but antagonists of protein kinase A (PKA) failed to block pinch
induced LTH. Thus the NO-cGMP-PKG pathway and at least one other pathway, but not
the cAMP-PKA pathway, are critical for inducing LTH after brief, noxious
stimulation.
PMID- 10195176
TI - Cyclic AMP induces functional presynaptic boutons in hippocampal CA3-CA1 neuronal
cultures.
AB - Long-term forms of synaptic plasticity that may underlie learning and memory have
been suggested to depend on changes in the number of synapses between presynaptic
and postsynaptic neurons. Here we have investigated a form of synaptic plasticity
in cultures of hippocampal CA3 and CA1 neurons related to the late phase of long
term potentiation, which depends on cAMP and protein synthesis. Using the
fluorescent dye FM 1-43 to label active presynaptic terminals, we find that a
membrane permeable analog of cAMP enhances the number of active presynaptic
terminals and that this effect requires protein synthesis.
PMID- 10195177
TI - Selective acquisition of AMPA receptors over postnatal development suggests a
molecular basis for silent synapses.
AB - Early in postnatal development, glutamatergic synapses transmit primarily through
NMDA receptors. As development progresses, synapses acquire AMPA receptor
function. The molecular basis of these physiological observations is not known.
Here we examined single excitatory synapses with immunogold electron-microscopic
analysis of AMPA and NMDA receptors along with electrophysiological measurements.
Early in postnatal development, a significant fraction of excitatory synapses had
NMDA receptors and lacked AMPA receptors. As development progressed, synapses
acquired AMPA receptors with little change in NMDA receptor number. Thus,
synapses with NMDA receptors but no AMPA receptors can account for the
electrophysiologically observed 'silent synapse'.
PMID- 10195178
TI - Regulation of morphological postsynaptic silent synapses in developing
hippocampal neurons.
AB - Many excitatory synapses are thought to be postsynaptically 'silent', possessing
functional NMDA but lacking functional AMPA glutamate receptors. The acquisition
of AMPA receptors at silent synapses may be important in synaptic plasticity and
neuronal development. Here we characterize a possible morphological correlate of
silent synapses in cultured hippocampal neurons. Initially, most excitatory
synapses contained NMDA receptors, but only a few contained detectable AMPA
receptors. Synapses progressively acquired AMPA receptors as the cultures
matured. AMPA receptor blockade increased the number, size and fluorescent
intensity of AMPA receptor clusters and rapidly induced the appearance of AMPA
receptors at 'silent' synapses. In contrast, NMDA receptor blockade increased the
size, intensity and number of NMDA receptor clusters and decreased the number of
AMPA receptor clusters, resulting in an increase in the proportion of 'silent'
synapses. These results suggest that the number of silent synapses is regulated
during development and by changes in synaptic activity.
PMID- 10195179
TI - Miniature synaptic events maintain dendritic spines via AMPA receptor activation.
AB - We investigated the influence of synaptically released glutamate on postsynaptic
structure by comparing the effects of deafferentation, receptor antagonists and
blockers of glutamate release in hippocampal slice cultures. CA1 pyramidal cell
spine density and length decreased after transection of Schaffer collaterals and
after application of AMPA receptor antagonists or botulinum toxin to unlesioned
cultures. Loss of spines induced by lesion or by botulinum toxin was prevented by
simultaneous AMPA application. Tetrodotoxin did not affect spine density.
Synaptically released glutamate thus exerts a trophic effect on spines by acting
at AMPA receptors. We conclude that AMPA receptor activation by spontaneous
vesicular glutamate release is sufficient to maintain dendritic spines.
PMID- 10195180
TI - Slowing of axonal transport is a very early event in the toxicity of ALS-linked
SOD1 mutants to motor neurons.
AB - Mutations in copper/zinc superoxide dismutase 1 (SOD1), primary causes of human
amyotrophic lateral sclerosis (ALS), provoke motor neuron death through an
unidentified toxic property. The known neurofilament-dependent slowing of axonal
transport, combined with the prominent misaccumulation of neurofilaments in ALS,
suggests that an important aspect of toxicity may arise from damage to transport.
Here we verify this hypothesis for two SOD1 mutations linked to familial ALS.
Reduced transport of selective cargoes of slow transport, especially tubulin,
arises months before neurodegeneration. For one mutant, this represents the
earliest detectable abnormality. Thus, damage to the cargoes or machinery of slow
transport is an early feature of toxicity mediated by mutant SOD1.
PMID- 10195181
TI - Neurological dysfunctions in mice expressing different levels of the Q/R site
unedited AMPAR subunit GluR-B.
AB - We generated mouse mutants with targeted AMPA receptor (AMPAR) GluR-B subunit
alleles, functionally expressed at different levels and deficient in Q/R-site
editing. All mutant lines had increased AMPAR calcium permeabilities in pyramidal
neurons, and one showed elevated macroscopic conductances of these channels. The
AMPAR-mediated calcium influx induced NMDA-receptor-independent long-term
potentiation (LTP) in hippocampal pyramidal cell connections. Calcium-triggered
neuronal death was not observed, but mutants had mild to severe neurological
dysfunctions, including epilepsy and deficits in dendritic architecture. The
seizure-prone phenotype correlated with an increase in the macroscopic
conductance, as independently revealed by the effect of a transgene for a Q/R
site-altered GluR-B subunit. Thus, changes in GluR-B gene expression and Q/R site
editing can affect critical architectural and functional aspects of excitatory
principal neurons.
PMID- 10195182
TI - Spread of dendritic excitation in layer 2/3 pyramidal neurons in rat barrel
cortex in vivo.
AB - In layer 2/3 pyramidal neurons of barrel cortex in vivo, calcium ion
concentration ([Ca2+]) transients in apical dendrites evoked by sodium action
potentials are limited to regions close to the soma. To study the mechanisms
underlying this restricted pattern of calcium influx, we combined two-photon
imaging of dendritic [Ca2+] dynamics with dendritic membrane potential
measurements. We found that sodium action potentials attenuated and broadened
rapidly with distance from the soma. However, dendrites of layer 2/3 cells were
electrically excitable, and direct current injections could evoke large [Ca2+]
transients. The restricted pattern of dendritic [Ca2+] transients is therefore
due to a failure of sodium action-potential propagation into dendrites. Also,
stimulating subcortical activating systems by tail pinch can enhance dendritic
[Ca2+] influx induced by a sensory stimulus by increasing cellular excitability,
consistent with the importance of these systems in plasticity and learning.
PMID- 10195183
TI - Associative learning modifies neural representations of odors in the insect
brain.
AB - Recording brain activity in vivo during learning is fundamental to understanding
how memories are formed. We used functional calcium imaging to track odor
representations in the primary chemosensory center of the honeybee, the antennal
lobe, while training animals to discriminate a rewarded odor from an unrewarded
one. Our results show that associative learning transforms odor representations
and decorrelates activity patterns for the rewarded versus the unrewarded odor,
making them less similar. Additionally, activity for the rewarded but not for the
unrewarded odor is increased. These results indicate that neural representations
of the environment may be modified through associative learning.
PMID- 10195184
TI - Predictive coding in the visual cortex: a functional interpretation of some extra
classical receptive-field effects.
AB - We describe a model of visual processing in which feedback connections from a
higher- to a lower-order visual cortical area carry predictions of lower-level
neural activities, whereas the feedforward connections carry the residual errors
between the predictions and the actual lower-level activities. When exposed to
natural images, a hierarchical network of model neurons implementing such a model
developed simple-cell-like receptive fields. A subset of neurons responsible for
carrying the residual errors showed endstopping and other extra-classical
receptive-field effects. These results suggest that rather than being exclusively
feedforward phenomena, nonclassical surround effects in the visual cortex may
also result from cortico-cortical feedback as a consequence of the visual system
using an efficient hierarchical strategy for encoding natural images.
PMID- 10195185
TI - Dissociation of visual, motor and predictive signals in parietal cortex during
visual guidance.
AB - The role of the posterior parietal cortex (PPC) in the visual guidance of
movements was studied in monkeys trained to use a joystick to guide a spot to a
target. Visual and motor influences were dissociated by transiently occluding the
spot and by varying the relationship between the direction of joystick and spot
movements. We found a strong segregation of function in PPC during visual
guidance. Neurons in area MST were selectively modulated by the direction of
visible moving stimuli, whereas neurons in area MIP were selectively modulated by
the direction of hand movement. In contrast, the selectivity of cells in the
lateral intraparietal area (LIP) did not directly depend on either visual input
or motor output, but rather seemed to encode a predictive representation of
stimulus movement. These predictive signals may be an important link in
visuomotor transformations.
PMID- 10195186
TI - Enhanced recognition memory following vagus nerve stimulation in human subjects.
AB - Neuromodulators associated with arousal modulate learning and memory, but most of
these substances do not freely enter the brain from the periphery. In rodents,
these neuromodulators act in part by initiating neural messages that travel via
the vagus nerve to the brain, and electrical stimulation of the vagus enhances
memory. We now extend that finding to human verbal learning. We examined word
recognition memory in patients enrolled in a clinical study evaluating the
capacity of vagus nerve stimulation to control epilepsy. Stimulation administered
after learning significantly enhanced retention. These findings confirm in humans
the hypothesis that vagus nerve activation modulates memory formation similarly
to arousal.
PMID- 10195188
TI - Overuse of impact factors suppresses controversial ideas.
PMID- 10195187
TI - Science and terrorism in Europe.
PMID- 10195189
TI - Speech boundaries, syntax and the brain.
PMID- 10195190
TI - Coupling calcium to SNARE-mediated synaptic vesicle fusion.
PMID- 10195191
TI - The smell of adrenaline.
PMID- 10195192
TI - Weighing the evidence: how the brain makes a decision.
PMID- 10195193
TI - Neurotrophin-3 is required for proper cerebellar development.
PMID- 10195194
TI - Snapin: a SNARE-associated protein implicated in synaptic transmission.
AB - Synaptic vesicle docking and fusion are mediated by the assembly of a stable
SNARE core complex of proteins, which include the synaptic vesicle membrane
protein VAMP/synaptobrevin and the plasmalemmal proteins syntaxin and SNAP-25. We
have now identified another SNAP-25-binding protein, called Snapin. Snapin was
enriched in neurons and exclusively located on synaptic vesicle membranes. It
associated with the SNARE complex through direct interaction with SNAP-25.
Binding of recombinant Snapin-CT to SNAP-25 blocked the association of the SNARE
complex with synaptotagmin. Introduction of Snapin-CT and peptides containing the
SNAP-25 binding sequence into presynaptic superior cervical ganglion neurons in
culture reversibly inhibited synaptic transmission. These results suggest that
Snapin is an important component of the neurotransmitter release process through
its modulation of the sequential interactions between the SNAREs and
synaptotagmin.
PMID- 10195195
TI - Casein kinase-II regulates NMDA channel function in hippocampal neurons.
AB - Several second-messenger-regulated protein kinases have been implicated in the
regulation of N-methyl-D-aspartate (NMDA) channel function. Yet the role of
calcium and cyclic-nucleotide-independent kinases, such as casein kinase II
(CKII), has remained unexplored. Here we identify CKII as an endogenous Ser/Thr
protein kinase that potently regulates NMDA channel function and mediates
intracellular actions of spermine on the channel. The activity of NMDA channels
in cell-attached and inside-out recordings was enhanced by CKII or spermine and
was decreased by selective inhibition of CKII. In hippocampal slices, inhibitors
of CKII reduced synaptic transmission mediated by NMDA but not AMPA receptors.
The dependence of NMDA receptor channel activity on tonically active CKII thus
permits changes in intracellular spermine levels or phosphatase activities to
effectively control channel function.
PMID- 10195196
TI - Adrenaline enhances odorant contrast by modulating signal encoding in olfactory
receptor cells.
AB - Olfactory perception is influenced by hormones. Here we report that adrenaline
can directly affect the signal encoding of olfactory receptor cells. Application
of adrenaline suppressed action potentials near threshold and increased their
frequency in response to strong stimuli, resulting in a narrower dynamic range.
Under voltage-clamp conditions, adrenaline enhanced sodium current and reduced T
type calcium current. Because sodium current is the major component of spike
generation and T-type calcium current lowers the threshold in olfactory receptor
cells, the effects of adrenaline on these currents are consistent with the
results obtained under current-clamp conditions. Both effects involved a common
cytoplasmic pathway, cAMP-dependent phosphorylation. We suggest that adrenaline
may enhance contrast in olfactory perception by this mechanism.
PMID- 10195197
TI - Microdomains for neuron-glia interaction: parallel fiber signaling to Bergmann
glial cells.
AB - Astrocytes are considered a reticulate network of cells, through which calcium
signals can spread easily. In Bergmann glia, astrocytic cells of the cerebellum,
we identified subcellular compartments termed 'glial microdomains'. These
elements have a complex surface consisting of thin membrane sheets, contain few
mitochondria and wrap around synapses. To test for neuronal interaction with
these structures, we electrically stimulated parallel fibers. This stimulation
increased intracellular calcium concentration ([Ca2+]i) in small compartments
within Bergmann glial cell processes similar in size to glial microdomains. Thus,
a Bergmann glial cell may consist of hundreds of independent compartments capable
of autonomous interactions with the particular group of synapses that they
ensheath.
PMID- 10195198
TI - Voltage-activated sodium channels amplify inhibition in neocortical pyramidal
neurons.
AB - Inhibitory postsynaptic potentials (IPSPs) in neocortical pyramidal neurons are
increased in duration and amplitude at depolarized membrane potentials. This
effect was not due to changes in the time course of the underlying synaptic
current. The role of postsynaptic voltage-activated channels was investigated by
mimicking the voltage change that occurs during an IPSP with current injections.
The peak and integral of these 'simulated' IPSPs increased during depolarization
of the membrane potential in a tetrodotoxin-sensitive manner. This amplification
presumably occurs as the hyperpolarization associated with IPSPs turns off sodium
channels that are tonically active at depolarized membrane potentials. IPSP
amplification increased the ability of IPSPs to inhibit action potential firing
and promoted IPSP-induced action potential synchronization.
PMID- 10195199
TI - Retention of heroin and morphine-6 beta-glucuronide analgesia in a new line of
mice lacking exon 1 of MOR-1.
AB - Morphine produces analgesia by activating mu opioid receptors encoded by the MOR
1 gene. Although morphine-6 beta-glucuronide (M6G), heroin and 6-acetylmorphine
also are considered mu opioids, recent evidence suggests that they act through a
distinct receptor mechanism. We examined this question in knockout mice
containing disruptions of either the first or second coding exon of MOR-1. Mice
homozygous for either MOR-1 mutation were insensitive to morphine. Heroin, 6
acetylmorphine and M6G still elicited analgesia in the exon-1 MOR-1 mutant, which
also showed specific M6G binding, whereas M6G and 6-acetylmorphine were inactive
in the exon-2 MOR-1 mutant. These results provide genetic evidence for a unique
receptor site for M6G and heroin analgesia.
PMID- 10195200
TI - SOD1 rescues cerebral endothelial dysfunction in mice overexpressing amyloid
precursor protein.
AB - Peptides derived from proteolytic processing of the beta-amyloid precursor
protein (APP), including the amyloid-beta peptide, are important for the
pathogenesis of Alzheimer's dementia. We found that transgenic mice
overexpressing APP have a profound and selective impairment in endothelium
dependent regulation of the neocortical microcirculation. Such endothelial
dysfunction was not found in transgenic mice expressing both APP and superoxide
dismutase-1 (SOD1) or in APP transgenics in which SOD was topically applied to
the cerebral cortex. These cerebrovascular effects of peptides derived from APP
processing may contribute to the alterations in cerebral blood flow and to
neuronal dysfunction in Alzheimer's dementia.
PMID- 10195201
TI - The construction of movement by the spinal cord.
AB - We used a computational analysis to identify the basic elements with which the
vertebrate spinal cord constructs one complex behavior. This analysis extracted a
small set of muscle synergies from the range of muscle activations generated by
cutaneous stimulation of the frog hindlimb. The flexible combination of these
synergies was able to account for the large number of different motor patterns
produced by different animals. These results therefore demonstrate one strategy
used by the vertebrate nervous system to produce movement in a computationally
simple manner.
PMID- 10195202
TI - Self-sustained rhythmic activity in the thalamic reticular nucleus mediated by
depolarizing GABAA receptor potentials.
AB - Intracellular recordings from reticular thalamic (RE) neurons in vivo revealed
inhibitory postsynaptic potentials (IPSPs) between RE cells that reversed and
became depolarizing at the hyperpolarized membrane potentials that occur during
sleep. These excitatory IPSPs can directly trigger low-threshold spikes (LTSs).
The oscillatory mechanisms underlying IPSP-triggered LTSs crowned by spike bursts
were investigated in models of isolated RE networks. In a one-dimensional network
model, external stimulation evoked waves of excitation propagating at a constant
velocity of 25-150 cells per second. In a large-scale, two-dimensional model of
the reticular nucleus, the network showed transient or self-sustained
oscillations controlled by the maximum conductance of the low-threshold calcium
current and the membrane potential. This model predicts that the isolated
reticular nucleus could initiate sequences of spindle oscillations in
thalamocortical networks in vivo.
PMID- 10195203
TI - Neural correlates of a decision in the dorsolateral prefrontal cortex of the
macaque.
AB - To make a visual discrimination, the brain must extract relevant information from
the retina, represent appropriate variables in the visual cortex and read out
this representation to decide which of two or more alternatives is more likely.
We recorded from neurons in the dorsolateral prefrontal cortex (areas 8 and 46)
of the rhesus monkey while it performed a motion discrimination task. The monkey
indicated its judgment of direction by making appropriate eye movements. As the
monkey viewed the motion stimulus, the neural response predicted the monkey's
subsequent gaze shift, hence its judgment of direction. The response comprised a
mixture of high-level oculomotor signals and weaker visual sensory signals that
reflected the strength and direction of motion. This combination of sensory
integration and motor planning could reflect the conversion of visual motion
information into a categorical decision about direction and thus give insight
into the neural computations behind a simple cognitive act.
PMID- 10195204
TI - Weighted combination of size and disparity: a computational model for timing a
ball catch.
AB - How do we time hand closure to catch a ball? Binocular disparity and optical
looming provide two sources of information about an object's motion in depth, but
the relative effectiveness of the two cues depends on ball size. Based on results
from a virtual reality ball-catching task, we derive a simple model that uses
both cues. The model is sensitive to the relative effectiveness of size and
disparity and implicitly switches its response to the cue that specifies the
earliest arrival and away from a cue that is lost or below threshold. We
demonstrate the model's robustness by predicting the response of participants to
some very unusual ball trajectories in a virtual reality task.
PMID- 10195205
TI - Brain potentials indicate immediate use of prosodic cues in natural speech
processing.
AB - Spoken language, in contrast to written text, provides prosodic information such
as rhythm, pauses, accents, amplitude and pitch variations. However, little is
known about when and how these features are used by the listener to interpret the
speech signal. Here we use event-related brain potentials (ERP) to demonstrate
that intonational phrasing guides the initial analysis of sentence structure. Our
finding of a positive shift in the ERP at intonational phrase boundaries suggests
a specific on-line brain response to prosodic processing. Additional ERP
components indicate that a false prosodic boundary is sufficient to mislead the
listener's sentence processor. Thus, the application of ERP measures is a
promising approach for revealing the time course and neural basis of prosodic
information processing.
PMID- 10195206
TI - Pros and cons of open peer review.
PMID- 10195207
TI - An ambiguous fast synapse: a new twist in the tale of two transmitters.
PMID- 10195208
TI - GABA and the single oocyte: relating binding to gating.
PMID- 10195209
TI - New neurons in old brains: learning to survive?
PMID- 10195210
TI - Now you see it: frontal eye field responses to invisible targets.
PMID- 10195211
TI - Social context modulates singing-related neural activity in the songbird
forebrain.
PMID- 10195212
TI - Hepatocyte growth factor, a versatile signal for developing neurons.
AB - Here we summarize recent findings on the biology of hepatocyte growth factor
(HGF, also known as scatter factor), focusing on its effects on developing
neurons. HGF is both a chemoattractant and a survival factor for embryonic motor
neurons. In addition, sensory and sympathetic neurons and their precursors
respond to HGF with increased differentiation, survival and axonal outgrowth. The
broad spectrum of HGF activities and its observed synergy with other neurotrophic
factors suggest that the major role of HGF is to potentiate the response of
developing neurons to specific signals.
PMID- 10195213
TI - Channel opening locks agonist onto the GABAC receptor.
AB - Determination of the activation mechanism of neurotransmitter-operated ion
channels has been hindered by a limited understanding of the relationship between
agonist binding and the gating of the integral ion pore. Here we describe a
[3H]ligand binding assay that enables us to make repeated binding measurements
from the same intact oocyte expressing recombinant human rho 1 GABAC receptors
and directly correlate the binding kinetics with electrophysiological
measurements. We have determined an association rate for GABA of about 10(5) M-1s
1; this is four orders of magnitude slower than diffusion, indicating GABA has
restricted access to its binding site. We also demonstrate that GABA dissociates
at two rates. Our data are consistent with the faster rate being the true
microscopic dissociation rate of GABA, with the slower rate occurring because the
opening of the pore detains agonist release.
PMID- 10195214
TI - Acetylcholine receptor M3 domain: stereochemical and volume contributions to
channel gating.
AB - By defining the functional defect in a congenital myasthenic syndrome (CMS), we
show that the third transmembrane domain (M3) of the muscle acetylcholine
receptor governs the speed and efficiency of gating of its channel. The clinical
phenotype of this CMS results from the mutation V285I in M3 of the alpha subunit,
which attenuates endplate currents, accelerates their decay and causes abnormally
brief acetylcholine-induced single-channel currents. Kinetic analysis of
engineered alpha V285I receptors demonstrated a predominant effect on channel
gating, with abnormally slow opening and rapid closing rates. Analysis of site
directed mutations revealed stereochemical and volume-dependent contributions of
alpha V285 to channel gating. Thus, we demonstrate a functional role for the M3
domain as a key component of the nicotinic acetylcholine receptor channel-gating
mechanism.
PMID- 10195215
TI - Activation of NMDA receptors reverses desensitization of mGluR5 in native and
recombinant systems.
AB - The metabotropic glutamate receptor, mGluR5, has a critical role in induction of
NMDA-receptor-dependent forms of synaptic plasticity and excitotoxicity. This is
likely mediated by a reciprocal positive-feedback interaction between these two
glutamate receptor subtypes in which activation of mGluR5 potentiates NMDA
receptor currents and NMDA receptor activation potentiates mGluR5-mediated
responses. We have investigated the mechanism by which NMDA receptor activation
modulates mGluR5 function and find evidence that this response is mediated by
activation of a protein phosphatase and a resultant dephosphorylation of protein
kinase C phosphorylation sites on mGluR5. This form of neuromodulation may be
important in a number of normal and pathological processes that involve
activation of the NMDA receptor.
PMID- 10195216
TI - Synaptic corelease of ATP and GABA in cultured spinal neurons.
AB - In the spinal dorsal horn (DH), transmission and modulation of peripheral
nociceptive (pain-inducing) messages involve classical neurotransmitters and
neuropeptides. We show that approximately half of DH neurons use ATP as a fast
excitatory neurotransmitter acting at ionotropic P2X postsynaptic receptors. ATP
was not codetected with glutamate but was coreleased with the inhibitory
neurotransmitter GABA. Moreover, adenosine, probably generated by extracellular
metabolism of ATP, finely tuned GABAergic inhibitory postsynaptic currents.
Differential modulation of excitatory versus inhibitory components of this mixed
cotransmission may help to explain changes in sensory message processing in the
DH during mechanical hyperalgesia and neuropathic pain.
PMID- 10195217
TI - Changes in cerebral cortex size are governed by fibroblast growth factor during
embryogenesis.
AB - We show that fibroblast growth factor 2 (FGF2) and FGF receptors are transiently
expressed by cells of the pseudostratified ventricular epithelium (PVE) during
early neurogenesis. A single microinjection of FGF2 into cerebral ventricles of
rat embryos at E15.5 increased the volume and total number of neurons in the
adult cerebral cortex by 18% and 87%, respectively. Microinjection of FGF2 by the
end of neurogenesis, at E20.5, selectively increased the number of glia. Mice
lacking the FGF2 gene had fewer cortical neurons and glia at maturity. BrdU
studies in FGF2-microinjected and FGF2-null animals suggested that FGF2 increases
the proportion of dividing cells in the PVE without affecting the cell-cycle
length. Thus, FGF2 increases the number of rounds of division of cortical
progenitors.
PMID- 10195218
TI - Neuronal growth cone collapse triggers lateral extensions along trailing axons.
AB - Axonal outgrowth is generally thought to be controlled by direct interaction of
the lead growth cone with guidance cues, and, in trailing axons, by fasciculation
with pioneer fibers. Responses of axons and growth cones were examined as
cultured retinal ganglion cell (RGC) axons encountered repellent cues. Either
contact with cells expressing ephrins or mechanical probing increased the
probability of lead growth cone retraction. Lateral extension of filopodia and
lamellipodia hundreds of microns behind the lead growth cone was correlated with
its collapse. Transmission electron microscopy showed that some of the lateral
extensions originate from the pioneer axon, whereas others represent growth cones
of defasciculating trailing axons.
PMID- 10195219
TI - Learning enhances adult neurogenesis in the hippocampal formation.
AB - Thousands of hippocampal neurons are born in adulthood, suggesting that new cells
could be important for hippocampal function. To determine whether hippocampus
dependent learning affects adult-generated neurons, we examined the fate of new
cells labeled with the thymidine analog bromodeoxyuridine following specific
behavioral tasks. Here we report that the number of adult-generated neurons
doubles in the rat dentate gyrus in response to training on associative learning
tasks that require the hippocampus. In contrast, training on associative learning
tasks that do not require the hippocampus did not alter the number of new cells.
These findings indicate that adult-generated hippocampal neurons are specifically
affected by, and potentially involved in, associative memory formation.
PMID- 10195220
TI - Running increases cell proliferation and neurogenesis in the adult mouse dentate
gyrus.
AB - Exposure to an enriched environment increases neurogenesis in the dentate gyrus
of adult rodents. Environmental enrichment, however, typically consists of many
components, such as expanded learning opportunities, increased social
interaction, more physical activity and larger housing. We attempted to separate
components by assigning adult mice to various conditions: water-maze learning
(learner), swim-time-yoked control (swimmer), voluntary wheel running (runner),
and enriched (enriched) and standard housing (control) groups. Neither maze
training nor yoked swimming had any effect on bromodeoxyuridine (BrdU)-positive
cell number. However, running doubled the number of surviving newborn cells, in
amounts similar to enrichment conditions. Our findings demonstrate that voluntary
exercise is sufficient for enhanced neurogenesis in the adult mouse dentate
gyrus.
PMID- 10195221
TI - Impaired synaptic plasticity and learning in aged amyloid precursor protein
transgenic mice.
AB - We investigated synaptic communication and plasticity in hippocampal slices from
mice overexpressing mutated 695-amino-acid human amyloid precursor protein
(APP695SWE), which show behavioral and histopathological abnormalities simulating
Alzheimer's disease. Although aged APP transgenic mice exhibit normal fast
synaptic transmission and short term plasticity, they are severely impaired in in
vitro and in-vivo long-term potentiation (LTP) in both the CA1 and dentate gyrus
regions of the hippocampus. The LTP deficit was correlated with impaired
performance in a spatial working memory task in aged transgenics. These deficits
are accompanied by minimal or no loss of presynaptic or postsynaptic elementary
structural elements in the hippocampus, suggesting that impairments in functional
synaptic plasticity may underlie some of the cognitive deficits in these mice
and, possibly, in Alzheimer's patients.
PMID- 10195222
TI - Complex cells as cortically amplified simple cells.
AB - The majority of synapses in primary visual cortex mediate excitation between
nearby neurons, yet the role of local recurrent connections in visual processing
remains unclear. We propose that these connections are responsible for the
spatial-phase invariance of complex-cell responses. In a network model with
selective cortical amplification, neurons exhibit simple-cell responses when
recurrent connections are weak and complex-cell responses when they are strong,
suggesting that simple and complex cells are the low- and high-gain limits of the
same basic cortical circuit. Given the ubiquity of invariant responses in
cognitive processing, the recurrent mechanism we propose for complex cells may be
widely applicable.
PMID- 10195223
TI - The detection of visual signals by macaque frontal eye field during masking.
AB - The neural link between a sensory signal and its behavioral report was
investigated in macaques trained to locate an intermittently detectable visual
target. Neurons in the frontal eye field, an area involved in converting the
outcome of visual processing into motor commands, responded at short latencies to
the target stimulus whether or not the monkey reported its presence. Neural
activity immediately preceding the visual response to the mask was significantly
greater on hits than on misses, and was significantly greater on false alarms
than on correct rejections. The results show that visual signals masked by light
are not filtered out at early stages of visual processing; furthermore, the
magnitude of early visual responses in prefrontal cortex predicts the behavioral
report.
PMID- 10195224
TI - Amygdala activity related to enhanced memory for pleasant and aversive stimuli.
AB - Pleasant or aversive events are better remembered than neutral events. Emotional
enhancement of episodic memory has been linked to the amygdala in animal and
neuropsychological studies. Using positron emission tomography, we show that
bilateral amygdala activity during memory encoding is correlated with enhanced
episodic recognition memory for both pleasant and aversive visual stimuli
relative to neutral stimuli, and that this relationship is specific to emotional
stimuli. Furthermore, data suggest that the amygdala enhances episodic memory in
part through modulation of hippocampal activity. The human amygdala seems to
modulate the strength of conscious memory for events according to emotional
importance, regardless of whether the emotion is pleasant or aversive.
PMID- 10195226
TI - Gp120 sequence variation in brain and in T-lymphocyte human immunodeficiency
virus type 1 primary isolates.
AB - OBJECTIVE: We sought to identify genetic determinants within human
immunodeficiency virus type 1 (HIV-1) gp120 that differentiate viral species in
brain from those in lymphocytes. STUDY DESIGN/METHODS: Polymerase chain reaction
(PCR) was used to amplify gp120 genes from paired brain and T-cell isolates from
two infants and two adults with dementia. Amplimers were molecularly cloned and
sequenced. RESULTS: The degrees of amino acid divergence between brain and T-cell
clones for the two adults were 7.7% and 8.6% and, for the two infants, 2.4% and
2.7%. For one adult and one infant, divergence was greater among brain cell
clones than T-cell clones. In the adults, a 3-amino acid insertion, located
similarly within V4 and encoding asparagine residues, was identified in the T
cell clones. CONCLUSIONS: HIV-1 genetic variation within brain cells is not
necessarily restricted compared with that in blood lymphocytes. The species in
brain cells can be distinguished from those in lymphocytes by determinants within
V4. These differences suggest that immune-mediated selection ongoing within
lymphoid cell compartments may not occur within brain.
PMID- 10195227
TI - Identification of a major latent nuclear antigen, LNA-1, in the human herpesvirus
8 genome.
AB - OBJECTIVES: Human herpesvirus 8 (HHV-8) is strongly associated with all forms of
Kaposi's sarcoma (KS) and with primary effusion lymphomas (PEL). KS patients'
sera are immunoreactive against discrete nuclear localizing antigens in PEL cell
lines. This study sought to identify and characterize these nuclear localizing
proteins. STUDY DESIGN/METHODS: KS patients' sera were used to screen a cDNA
expression library derived from a PEL cell line (BCP-1) latently infected with
HHV-8. RESULTS: An HHV-8-specific cDNA clone was isolated. It encoded one partial
and two complete open reading frames (ORFs): ORF 73, ORF 72 (v-cyclin), and K13,
respectively. The immunodominant epitope was mapped to the C-terminal domain of
ORF 73. Analysis with the KS patients' sera of HEK 293 cells transfected with a
clone encompassing the complete coding region of ORF 73, ORF 72, and K13 gave a
nuclear immunofluorescence pattern similar to that observed in BCP-1 cells.
Western blot analysis with KS patients' sera of transfected HEK 293 cells
revealed an immunoreactive protein of 220 to 230 kD that was similar to that
observed previously in PEL cell lines. After induction of lytic replication of
HHV-8 in BCP-1 cells with n-butyrate, we observed a major reduction in the
expression of an ORF 73-specific 6.6-kb mRNA, indicating that this region is
under latent control. CONCLUSIONS: These data identify a region of HHV-8 encoding
for a major immunoreactive latent nuclear antigen (LNA-1), analogous to the
Epstein-Barr virus latent nuclear antigens.
PMID- 10195228
TI - Correlation of tumor suppressor P53 RNA expression with human immunodeficiency
virus disease in rapid and slow progressors.
AB - OBJECTIVE: To determine the relation between P53 tumor suppressor RNA expression
and human immunodeficiency virus (HIV) disease progression. STUDY DESIGN/METHODS:
A quantitative assay of P53 RNA expression was used to analyze a cohort of HIV
negative persons. The assay was then used in longitudinal and cross-sectional
studies of HIV slow and rapid progressors. RESULTS: We demonstrate first that P53
expression in peripheral blood mononuclear cells from HIV-1-seronegative persons
is minimal. Longitudinal studies in a small cohort of HIV-1-infected slow and
rapid progressors reveal that rapid progressors seem to have greater P53 RNA
expression over time. This was validated in a cohort of 26 HIV-1-infected persons
in whom the expression of P53 RNA was significantly greater in persons with rapid
progression of HIV-1 disease. CONCLUSION: These data suggest that P53 RNA
expression may play a role in the pathogenesis of HIV-1 disease, though the
mechanism of this interaction remains unknown.
PMID- 10195229
TI - Mother-to-child transmission of human T-cell lymphotropic virus type I associated
with prolonged breast-feeding.
AB - OBJECTIVES: We assessed the risk of transmitting human T-cell lymphotropic virus
type I (HTLV-I) through breast-feeding. STUDY DESIGN/METHODS: To assess the risk
of mother-to-child transmission of HTLV-I, 212 HTLV-I-seropositive women and 145
HTLV-I-seronegative women were enrolled in a prospective cohort study conducted
in Kingston, Jamaica. Their offspring were examined at regular intervals, and
HTLV-I serostatus was determined at each visit. RESULTS: Twenty-eight of the 181
children with at least one postnatal visit born to HTLV-I-seropositive women (and
none of the children born to HTLV-I-seronegative women) were persistently
seropositive and were considered HTLV-I infected (Kaplan-Meier estimated
cumulative incidence, 18%; 95% CI, 12%-24%). Among children observed for at least
24 months, 19 (32%) of 60 children breast fed for 12 months or longer were HTLV-I
seropositive, compared with only 8 (9%) of 86 children breast-fed for less than
12 months (relative risk, 3.4; 95% CI, 1.7-6.9). Compared with children weaned at
younger ages, transmission of HTLV-I was associated with continued breast-feeding
of children who were 12 to 18 months of age (relative hazard, 6.4; 95% CI, 2.1
180.2) and older than 18 months (relative hazard, 18.1; 95% CI, 1.4-29.5).
Transmission was also associated with higher maternal antibody titer (a possible
marker of virus load), prolonged duration of ruptured membranes during
childbirth, and lower maternal income. CONCLUSIONS: These results suggest that
limiting the duration of breast-feeding to less than 12 months for children born
to HTLV-I-seropositive mothers may significantly reduce mother-to-child
transmission of HTLV-I.
PMID- 10195230
TI - Diagnostic challenges for rapid human immunodeficiency virus assays. Performance
using HIV-1 group O, HIV-1 group M, and HIV-2 samples.
AB - OBJECTIVE: We sought to determine the ability of seven rapid assays for human
immunodeficiency virus (HIV) to detect antibodies in a panel of sera from
individuals infected with different types and groups of HIV. STUDY
DESIGN/METHODS: Sixty-eight well-characterized samples, including HIV-1 group O
(24), several HIV-1 group M clades (21), HIV-1/2 (10), HIV-2 (10), and samples
with indeterminate results (3), were tested by the following rapid HIV assays:
HIV-Spot, HIVCHEK System 3, A/Q Rapid HIV, Genie II HIV-1/HIV-2, Quix HIV-1-2-O,
ImmunoComb II HIV-1+2 BiSpot, and the Serodia HIV-1+2. RESULTS: All tests
successfully detected the HIV-1 group M clades and the HIV-1/2-positive samples.
Of the HIV-2 stand-alone samples, four tests missed the same sample, and three
tests missed another sample. Of the HIV-1 group O samples, four samples were
missed by at least one test, and another sample was missed by three tests. The
sensitivity of the seven rapid assays in detecting each group of sera was between
83% and 100%, with only one test having a sensitivity of 100% for all groups of
sera. Three samples proved to be problematic because they were misclassified by
more than one assay. CONCLUSIONS: The performance of rapid HIV assays is variable
when testing sera from individuals infected with HIV-1 group O and HIV-2.
PMID- 10195231
TI - Prevalence of specific IgA and IgM anti-HBc antibodies compared with HBV DNA in
the sera of HBsAg chronic carriers.
AB - OBJECTIVE: We evaluated the significance of IgA antibodies directed against the
hepatitis B virus core antigen (IgA anti-HBc) as a marker for viral replication.
STUDY DESIGN/METHODS: Serum samples of 143 hepatitis B surface antigen (HBsAg)
carriers and 189 HBsAg-negative subjects were studied. Hepatitis B virus (HBV)
DNA was detected by polymerase chain reaction. IgA anti-HBc was determined by a
capture enzyme-linked immunosorbent assay developed in our laboratory. The
results were compared with those for IgM anti-HBc, which were determined by a
commercially available method. RESULTS: IgA anti-HBc was detected in 57 (40%) and
HBV DNA in 38 (27%) of the HBsAg carriers. Among the HBsAg-negative subjects, IgA
anti-HBc and HBV DNA were detected simultaneously in four samples. All 42 HBV DNA
positive samples were IgA anti-HBc positive. IgM anti-HBc was detected in 27
(64%) of them. CONCLUSIONS: IgA anti-HBc is a sensitive marker for HBV
replication, and its absence may exclude HBV replication. The role of IgA anti
HBc in monitoring response to therapy and predicting clinical course is being
evaluated.
PMID- 10195232
TI - Optimization, assessment, and proposed use of a direct nested reverse
transcription-polymerase chain reaction protocol for the detection of hepatitis C
virus.
AB - OBJECTIVES: To compare the performance of reverse transcription followed by the
polymerase chain reaction (RT-PCR), without RNA purification, with the
performance of classic protocols. STUDY DESIGN/METHODS: Direct and classic
techniques were used to test three groups of samples: six hepatitis C virus (HCV)
seroconversion panels (n = 90), a HCV RNA reference panel (n = 26), and serial
dilutions of four HCV-positive sera (n = 24). These methods were then applied
sequentially through a clinical diagnostic algorithm to test 268 samples from
high-risk patients. RESULTS: For the three groups of samples, we found a 94%
concordance between direct and purified RT-PCR methods. For the detection of HCV
RNA in clinical samples, sensitivity was maximized and cost minimized using both
protocols according to the proposed algorithm. CONCLUSIONS: The direct PCR method
is reliable, sensitive, and can result in time and cost savings. The suggested
testing algorithm can enhance sensitivity and time savings for populations with a
high prevalence of infection.
PMID- 10195233
TI - Post-HAART therapy research.
PMID- 10195234
TI - Interferon downregulates CXCR4 (fusin) gene expression in peripheral blood
mononuclear cells.
AB - OBJECTIVE: Cytokines modulate human immunodeficiency virus type 1 (HIV-1)
replication at multiple stages of its life cycle. We examined the effects of
several HIV-1-stimulatory and HIV-1-inhibitory cytokines on CXCR4 (fusin) gene
expression in lymphoid cells. STUDY DESIGN/METHODS: Peripheral blood mononuclear
cells (PBMCs) were treated with various cytokines, and CXCR4 gene expression was
assessed by Northern blot analysis. Cell-cell fusion was assessed using HeLa-MAGI
cells expressing T-cell-tropic HIV-1 (i.e., LAV strain) envelope glycoproteins
and U937 cells expressing HIV-1 tat. RESULTS: Although treatment of PBMCs with
interferon-alpha (IFN-alpha) and IFN-gamma led to a significant repression of
CXCR4 gene expression, interleukin-1 beta (IL-1 beta), IL-6, and tumor necrosis
factor-alpha (TNF-alpha) had no significant effect on CXCR4 gene expression in
PBMCs. IFN-alpha and IFN-gamma also inhibited CXCR4 gene expression in the
promyelocytic cell line U937, and this inhibition led to a decrease in cell-cell
fusion between U937 cells and HeLa-MAGI cells. In U937 cells, TNF-alpha and
phorbol myristate acetate (PMA) stimulated CXCR4 gene transcription; this effect
was reversed with prior treatment of cells with IFN-gamma. CONCLUSIONS: IFN-alpha
and IFN-gamma effectively downmodulate fusin gene expression in lymphoid cells,
indicating that IFNs modulate HIV-1 replication at postentry levels as well as at
the level of HIV-1 entry.
PMID- 10195235
TI - Tumor necrosis factor alpha and human immunodeficiency virus-specific functional
immune responses after immunization with Gp120-depleted, inactivated HIV-1 in
incomplete Freund's adjuvant (REMUNE) in HIV-1-seropositive subjects.
AB - OBJECTIVE: We examined the relation between tumor necrosis factor-alpha (TNF
alpha) levels and human immunodeficiency virus type 1 (HIV-1)-specific functional
immune responses, as measured by HIV-1 antigen-stimulated lymphocyte
proliferation and beta-chemokine production after immunization with gp120
depleted, inactivated HIV-1 in incomplete Freund's adjuvant (i.e., HIV-1
Immunogen; REMUNE, The Immune Response Corporation, Carlsbad, CA, U.S.A.). STUDY
DESIGN/METHODS: HIV-1-seropositive subjects who enrolled in an open-label study
were immunized with REMUNE every 12 weeks and monitored for 60 weeks. HIV-1
antigen-stimulated lymphocyte proliferation and RANTES production were measured
in peripheral blood mononuclear cells (PBMCs). TNF-alpha levels were measured in
serum. RESULTS: TNF-alpha (P = 0.0003) significantly decreased and HIV-1 antigen
stimulated RANTES production (P = 0.002) and lymphocyte proliferation (P = 0.07)
increased after immunization with REMUNE. TNF-alpha levels negatively correlated
with HIV-1 antigen-stimulated RANTES production (r = -0.71; P = 0.0002) and
lymphocyte proliferation (r = -0.37; P = 0.09). CONCLUSIONS: This study
demonstrated decreased TNF-alpha levels with a concomitant augmentation of HIV
specific functional immunity in subjects immunized with REMUNE. Because TNF-alpha
has been implicated in the induction of anergy in HIV-1 infection, the ability to
decrease TNF-alpha may allow the immune system to respond to HIV and non-HIV
antigens. Larger studies are being conducted to confirm the clinical utility of
REMUNE in combination with potent antiviral drugs.
PMID- 10195237
TI - Five human immunodeficiency virus type 1 phenotypic variants with different MT-2
cell tropisms correlate with prognostic markers of disease.
AB - OBJECTIVES: We correlated virologic and immunologic parameters of disease
progression with cytopathogenicity of HIV isolates. STUDY DESIGN/METHODS: Human
immunodeficiency virus type 1 (HIV-1) isolates from 207 patients with CD4+ cell
counts < 500/mm3 were examined for biologic phenotype in MT-2 cells. We used a
cross-sectional study design. RESULTS: Three subtypes of syncytium-inducing (SI)
strains with different times of appearance of syncytia formation in cell culture
and two subtypes of non-syncytium-inducing (NSI) isolates, with (NSI/MT2+) or
without (NSI/MT2-) replicative capacity in MT-2 cells, were identified. Early SI
strains were associated with the lowest CD4+ cell counts and the highest levels
of viral load, and NSI/MT2- isolates correlated with the highest CD4+ cell counts
and the lowest viral loads. Patients with late SI and NSI/MT2+ strains showed
minimal differences in immunologic and virologic markers. CONCLUSIONS: Five HIV
phenotypic variants that correlate significantly (P < 0.001) with markers of
disease progression were identified.
PMID- 10195236
TI - AIDS-related Kaposi's sarcoma patients with visceral manifestations. Response to
human chorionic gonadotropin preparations.
AB - OBJECTIVE: In vitro cell culture studies and a murine model for human Kaposi's
sarcoma (KS) have shown that human chorionic gonadotropin (hCG)-associated factor
(HAF) isolated from commercial hCG preparations has antiproliferative and cell
killing effects on neoplastic KS cells, without toxic effects on normal
endothelial cells and lymphocytes. These findings prompted preliminary study of
hCG preparations for patients with early-stage KS with skin lesions only and no
known visceral involvement. Complete or partial regression of the skin lesions
occurred after intralesional injections of hCG (hCG-Pregnyl, hCG-APL). The
current study sought to extend these early observations to evaluation of the
safety of hCG in acquired immunodeficiency syndrome (AIDS) KS patients with
aggressive disease and visceral involvement. These patients present in a more
advanced stage of the disease that is coupled with serious immunodeficiency. They
commonly respond poorly to conventional chemotherapy and have a reduced median
life expectancy of only 4 to 9 months. STUDY DESIGN/METHODS: After approval by
the local institutional review boards, 13 patients with advanced AIDS-KS gave
informed consent and were treated with hCG preparations. These hCG preparations
are known to have antiproliferative activity in laboratory tests. Patients were
monitored for tumor size by clinical evaluation, ultrasonography, radiography,
respiratory functions, and endoscopic examination. Histologic examinations of
biopsied tissues were used for studies of apoptosis using in situ hybridization
techniques. The patients were also monitored for CD4+ T-cell numbers and human
immunodeficiency virus type 1 (HIV-1) plasma viral load according to common
clinical practice. RESULTS: Thirteen patients with advanced AIDS-KS and visceral
KS were treated with hCG. Five of 13 (38%) patients had dramatic responses to
therapy, and overall tolerance to the drug was excellent for all patients. Some
hCG preparations also showed beneficial effects against HIV-associated markers.
An accompanying decrease in viral load (plasma HIV-1 RNA) was observed in one
patient, a dramatic increase in CD4+ cells occurred in another, and significant
weight gain was seen in seven patients. CONCLUSIONS: These clinical observations
suggest that patients with aggressive visceral forms of KS, usually indicative of
an extremely poor prognosis and poor response to combined chemotherapy, can
benefit from this new therapeutic approach. In some patients, these preparations
also induce several other beneficial effects, such as weight gain, reduction in
HIV-1 RNA load, or increase in the CD4+ T-cell count. Additional controlled
clinical trials comparing this new therapeutic option with standard cytotoxic
chemotherapy are needed. These trials should be extended to patients with KS not
related to HIV-1 infection. Because we showed elsewhere that pure hCG had no
effect on KS, identification and subsequent clinical use of the active molecules
in hCG preparations is urgently needed.
PMID- 10195238
TI - Prevalence of hepatitis G virus RNA in human immunodeficiency virus type 1
positive intravenous drug users.
AB - OBJECTIVE: The aim of this study was to evaluate the prevalence of the new human
flavivirus hepatitis G virus (HGV) in Italian intravenous drug users (IDUs) and
its interaction with human immunodeficiency virus type 1 (HIV-1) and hepatitis C
virus (HCV). STUDY DESIGN/METHODS: Seventy-nine IDUs with different clinical
stages of HIV-1 infection and 20 non-IDU patients with chronic HCV infection were
included in the study. HGV RNA was detected by means of reverse transcription
polymerase chain reaction (RT-PCR) used for the amplification of two HGV-related
sequences included in the 5'-noncoding (NCR) and NS5a regions. RESULTS: Eighteen
(22.8%) of the 79 IDUs were positive for plasma HGV RNA; there was no difference
in mean serum alanine aminotransferase (ALT) levels between the HGV-positive and
HGV-negative patients. No significant correlation was observed between HGV and
other viral markers (hepatitis B virus [HBV], HCV, human T-cell lymphotropic
virus type II [HTLV-II]) or HCV genotype. The number of patients with symptomatic
HIV-1 infection in whom HGV RNA was detected was significantly lower than the
number of those who were asymptomatic (6 of 49 [12.2%] versus 12 of 30 [40%]; P =
0.004). The mean plasma HGV RNA titer was higher in the asymptomatic than in the
symptomatic patients (4.6 versus 3.2 log PCR-amplified units in 1 mL of plasma
sample [PU/mL]; P = 0.03). CONCLUSIONS: Our results show a considerable spread of
HGV levels among Italian HIV-1-positive IDUs and do not indicate that HGV
infection enhances liver impairment. We suggest that the greater prevalence of
HGV RNA in IDUs with asymptomatic HIV-1 infection may reflect the relatively
recent HGV infection in this population.
PMID- 10195239
TI - Transformation of guinea pig leukocytes by coinfection with human T-cell
lymphotropic virus types I and II.
AB - OBJECTIVE: The susceptibility of guinea pigs to human T-cell lymphotropic virus
(HTLV) infection and of their cardiac blood mononuclear cells (CBMCs) to HTLV
induced transformation were investigated. STUDY DESIGN/METHODS: Guinea pig CBMCs
were cocultured with HTLV-infected cell lines. Guinea pigs were then inoculated
with transformed guinea pig CBMCs. RESULTS: The coculture experiment gave rise to
a guinea pig cell line, GP-1, that was coinfected with both HTLV-I and HTLV-II as
shown by immunofluorescence staining, electron microscopy, polymerase chain
reaction (PCR) using primers specific for the pol region of each virus, and
Southern blot hybridization. The GP-1 cell line expressed T-cell markers and
monocyte/macrophage markers. Three guinea pigs given an intraperitoneal
inoculation of GP-1 cells seroconverted for HTLV-I and became positive for HTLV
I, HTLV-II, or both, as confirmed by PCR. CONCLUSIONS: Guinea pigs and their
CBMCs can be infected with HTLV-I and HTLV-II. This animal system may be useful
as an experimental model of HTLV-I and HTLV-II infection.
PMID- 10195240
TI - HIV-1, HHV-8, and Kaposi's sarcoma.
PMID- 10195241
TI - Inheritance pattern of mutant human immunodeficiency virus type 1 coreceptor gene
CCR5 in an Indian family.
AB - The most common form of mutation found in the CCR5 gene has been the precise 32
base pair (bp) deletion in the region corresponding to second extracellular loop
of the chemokine receptor CCR5. Individuals homozygous for the delta 32 allele of
CCR5 usually remain uninfected despite multiple exposures to HIV, whereas
heterozygous individuals support less virus replication and show slower
progression of the disease. This mutant allele in either homozygous or
heterozygous form is quite common in white people of European heritage. Earlier
work involving large populations of Asians and Africans failed to detect the
presence of this mutant allele. We screened 145 normal unrelated healthy Indians
and found one person who was heterozygous for the delta 32 allele of CCR5. We
studied the inheritance of this deleted allele in this person's family. One
parent, one of two sons, and the only daughter possessed this mutant allele. We
cloned the entire coding region of wild-type and mutant alleles of CCR5 gene from
the heterozygous individual mentioned and studied its coreceptor functions. The
mutant allele had only a moderate interfering effect on coreceptor activity of
the wild-type CCR5 allele in a cell fusion assay. We also report an improved
method of genotyping CCR5 gene in this communication.
PMID- 10195242
TI - Kaposi's sarcoma in the Gambia, West Africa is less frequent in human
immunodeficiency virus type 2 than in human immunodeficiency virus type 1
infection despite a high prevalence of human herpesvirus 8.
AB - OBJECTIVES: To investigate the distribution of Kaposi's sarcoma (KS) cases in
patients with human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2)
infection in the Gambia; to document the prevalence of human herpesvirus 8 (HHV
8) infection in various population groups in the Gambia. STUDY DESIGN/METHODS: A
retrospective analysis of KS cases in hospital records at the Medical Research
Council (MRC) hospital was performed, along with a cross-sectional survey of HHV
8 prevalence in hospital-based and community-based study population with
polymerase chain reaction (PCR) and serologic assays. RESULTS: After adjusting
for gender and CD% at the first visit, HIV-1-positive patients were 12.4 times
more likely to have KS than were HIV-2-positive patients. The prevalence of
antibodies to HHV-8 and the HHV-8 genome was high in both HIV-1-positive and HIV
2-positive patients without KS. The prevalence of antibodies was also high in
pregnant women who were HIV-1-positive, HIV-2-positive, or HIV-negative (73%,
83%, and 79%, respectively). CONCLUSIONS: HHV-8 infection is widespread in the
Gambia. In addition to immunosuppression and HHV-8 infection, other cofactors
specifically related to HIV-1 rather than HIV-2 appear to be involved in the
development of KS.
PMID- 10195243
TI - JC virus type 2B is found more frequently in brain tissue of progressive
multifocal leukoencephalopathy patients than in urine from controls.
AB - OBJECTIVES: Previous studies have shown that strains of human polyomavirus JC
(JCV) of Asian origin (type 2) are much more highly represented in progressive
multifocal leukoencephalopathy (PML) brain than would be expected from their
frequency of excretion in urine samples of a comparable control group. The
present studies were designed to test whether one subtype of type 2 was
preferentially elevated. STUDY DESIGN/METHODS: The statistical relation between
JCV subtypes represented in PML brain tissue from 51 probands and those in urine
samples from 115 control individuals was examined. RESULTS: The proportion of the
JCV subtype 2B in PML brain (36%) was highly significantly increased relative to
its occurrence in control urine samples (5.9%; P < .001). Type 1 and its subtypes
were not different in the PML brain and control urine cohorts. The number of type
4 strains in PML brains was reduced, although the difference did not reach
statistical significance (P = .08). CONCLUSIONS: The results predict that the
human immunodeficiency virus (HIV)-positive individuals at highest risk of PML
infection are those carrying the JCV genotype known as type 2B. Prospective
studies will be required to confirm this finding.
PMID- 10195244
TI - Seroprevalence of Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 in
several regions of Italy.
AB - OBJECTIVE: To study the seroprevalence of Kaposi's sarcoma-associated
herpesvirus/human herpesvirus type 8 (KSHV/HHV-8) in 779 Italian blood donors.
STUDY DESIGN/METHODS: Sera were tested for antibodies to a latency-associated
nuclear antigen (LANA) and a capsid related protein encoded by ORF65. RESULTS:
Among all Italian donors, 17.7% and 18.7% had antibodies to LANA and ORF65
protein, respectively, and 24.1% had antibodies to at least one antigen. KSHV/HHV
8 seroprevalence was higher in the Po valley and in Sardinia than close to the
sub-Alpine Veneto region, Tuscany, or Apulia. KSHV/HHV-8 seroprevalence was
almost equally distributed between men and women but increased in the older age
groups. CONCLUSIONS: The regional differences and age distribution in
seroprevalence agree partially with the incidence of classic KS in Italy. The
rarity of classic KS in KSHV/HHV-8-infected subjects and the equal gender
distribution of seroprevalence suggest that other cofactors may contribute to KS
development in human immunodeficiency virus type 1 (HIV-1)-uninfected
individuals.
PMID- 10195245
TI - Mammary epithelial cells support and transfer productive human T-cell
lymphotropic virus infections.
AB - OBJECTIVES: To investigate whether luminal and basal human mammary epithelial
cells (HMEC) are susceptible to productive infection by human T-cell lymphotropic
virus types I and II (HTLV-I and HTLV-II) and whether HTLV infection of breast
epithelial cells could contribute to the seeding of milk with HTLV infectivity
and support virus transmission from mother to nursing infant. STUDY
DESIGN/METHODS: Primary cultures of basal epithelial cells were infected by
coculture with mitomycin-C-treated HTLV-producer T-cell lines and HTLV-infected
milk epithelial cells, and the transfer of infection was monitored by polymerase
chain reaction (PCR) amplification and immunocytochemical staining. RESULTS:
Basal mammary epithelial cells were found to be susceptible to HTLV infection and
capable of transferring HTLV infection to normal peripheral blood lymphocytes
(PBL). CONCLUSIONS: A reservoir for HTLV infectivity could exist in mammary
epithelial cells and contribute to the introduction of HTLV infectivity into milk
by infecting lymphocytes that traverse the epithelium and by the release of
infected epithelial cells, infectious cell fragments, and free virions directly
into the milk.
PMID- 10195246
TI - Evolution of human immunodeficiency virus type 1 in relation to disease
progression in children.
AB - OBJECTIVE: To compare patterns of nonsynonymous and synonymous substitutions over
time in the V1V2 and C2V3 regions of human immunodeficiency virus type 1 (HIV-1)
env and in a conserved segment of pol in HIV-1-infected children with varying
rates of CD4+ T-cell decline. STUDY DESIGN/METHODS: Longitudinal study of HIV-1
genetic variants sampled from peripheral blood of 3 children affected with
acquired immunodeficiency syndrome (AIDS) and 4 children with slow disease
progression. Nested polymerase chain reaction (PCR) was used to detect HIV-1
genetic material in plasma-derived virions and cellular DNA. Sequence variants
were enumerated by screening cloned PCR products using heteroduplex mobility
assay (HMA) or single-strand conformation polymorphism analysis (SSCP) and
nucleotide sequencing. Frequencies of nonsynonymous and synonymous substitutions
within sampling points and the accumulation rate of nucleotide substitutions over
the period of observation were calculated. RESULTS: In the C2V3 region, higher
rates of accumulation of nonsynonymous substitutions were associated with more
precipitous declines in CD4+ cell numbers. In the V1V2 region, rates of
accumulation of nonsynonymous substitutions were comparable with those in the
C2V3 region, but similar rates were observed in AIDS-affected children and
children with slow disease progression. The rate of accumulation of nonsynonymous
substitutions in the pol region was lower than that in the C2V3 and V1V2 regions.
CONCLUSIONS: Rates of accumulation of nucleotide substitutions vary across the
HIV-1 genome and differ in relation to disease progression in children. The
finding of greater rates of nonsynonymous substitution in the immunodominant C2V3
region in children whose disease progressed rapidly is consistent with a vigorous
but inadequate immune response in children who are unable to control HIV-1
infection.
PMID- 10195247
TI - Cotransfection of mutated forms of human immunodeficiency virus type 1 Gag-Pol
with wild-type constructs can interfere with processing and viral replication.
AB - OBJECTIVES: We wished to generate a number of genetic constructs containing
mutations in the protease (PR) and reverse transcriptase (RT) genes of the Gag
Pol of human immunodeficiency virus type 1 (HIV-1) and to transfect these
constructs into COS-7 cells to determine their effect on wild-type (wt) viral
replication. RESULTS: The mutated Gag-Pol polyproteins were incorporated into
viral particles. Gag-Pol proteins that were mutated in PR as well as combinations
of mutations in PR and RT inhibited the production of fully processed and
infectious viral particles when these constructs were coexpressed with the
infectious HIV-1 molecular clone pBH10. Viral particles produced after
cotransfection of COS-7 cells with both pBH10 and infectious constructs
containing Gag-Pol, mutated in PR alone or in both RT and PR, showed abnormal
processing and lower infectivity. Complementation experiments in which pBH10
mutated in PR was coexpressed with wt Gag-Pol showed that the latter could be
incorporated into the viral particles that were generated. COS-7 cells stably
transfected with Gag-Pol, mutated in PR or in both PR and RT, and subsequently
transfected with pBH10, produced levels of p24 and RT activity that were
substantially diminished in comparison with levels produced by cells transfected
with wt pBH10 alone. CONCLUSIONS: These results suggest that trans-dominant
effects were potentially responsible for the observed inhibition of viral
replication.
PMID- 10195248
TI - Tat toxoid: its potential role as an HIV vaccine.
PMID- 10195249
TI - Lipopolysaccharide from an Escherichia coli htrB msbB mutant induces high levels
of MIP-1 alpha and MIP-1 beta secretion without inducing TNF-alpha and IL-1 beta.
AB - OBJECTIVE: To identify a lipopolysaccharide (LPS) that retains the capacity to
induce beta-chemokine secretion without the concomitant activation of pyrogenic
cytokines. METHODS: LPS was extracted from strain MLK986 (mLPS), an htrB1::Tn10,
msbB::ocam mutant of Escherichia coli that is defective for lipid A synthesis,
and from wild-type parent E coli strains, W3110 (wtLPS). The capacity of these
LPS preparations to induce tumor necrosis factor-alpha (TNF-alpha), interleukin-1
beta (IL-1 beta), and macrophage inflammatory proteins 1 alpha (MIP-1 alpha) and
MIP-1 beta was assessed using a human peripheral blood mononuclear cell (PBMC)
activation assay. RESULTS: Stimulation of PBMCs with mLPS did not induce
measurable levels of pyrogenic cytokines TNF-alpha and IL-1 beta, whereas wtLPS
induced high levels of these cytokines. Furthermore, mLPS antagonized the
induction of TNF-alpha secretion by wtLPS. Nonetheless, mLPS retained a discrete
agonist activity that induced MIP-1 alpha and MIP-1 beta secretion by PBMCs. This
latter agonist activity appears to be unique to mLPS, since two previously
documented LPS antagonists, Rhodobacter sphaeroides diphosphoryl lipid A and
synthetic lipid IVA, did not induce MIP-1 alpha and MIP-1 beta secretion.
Furthermore, synthetic lipid IVA was an antagonist of MIP-1 alpha and MIP-1 beta
induction by mLPS. CONCLUSION: These results show that mLPS exhibits a novel
bipartite activity, being an effective antagonist of TNF-alpha induction by
wtLPS, while paradoxically being an agonist of MIP-1 alpha and MIP-1 beta
secretion.
PMID- 10195250
TI - Stimulation of bystander T-cell proliferation by tumor necrosis factor produced
by HIV-1-infected macrophages.
AB - OBJECTIVE: Cocultivation of the CD4+CD95+ T-cell line (MT4) with monocyte-derived
macrophages (MDMs) infected with the HIV-1 resulted in costimulation of
proliferation and apoptosis after 20 hours of contact. This study sought to
determine whether tumor necrosis factor (TNF) produced by HIV-1-infected MDMs was
involved in the costimulation of cell proliferation, the apoptotic pathway, or
both. STUDY DESIGN/METHODS: MT4 cells were cocultivated with infected or
noninfected MDMs in the presence or absence of soluble TNF receptors (sTNFRs) or
antagonistic anti-Fas antibody (ZB4). Cell proliferation was assessed by
measuring thymidine incorporation. Apoptosis was monitored by using flow
cytometry and enzyme-linked immunosorbent assay (ELISA). RESULTS: Thymidine
incorporation was higher in cells cocultivated with HIV-infected or noninfected
MDMs than it was in controls grown in culture medium. It also was higher in cells
cocultivated with HIV-infected MDMs than it was in cells cocultivated with
noninfected MDMs. sTNFRs blocked the increase of thymidine incorporation
specifically induced by HIV-infected MDMs. They did not inhibit apoptosis at 20
hours. Cells recovered from cocultures involving HIV-infected or noninfected MDMs
exhibited decreased sensitivity to apoptosis induced through the Fas receptor.
CONCLUSION: TNF produced by HIV-infected MDMs acts as an accessory T-cell growth
factor that synergizes with an as yet unidentified growth-inducing signal or
signals produced by HIV-infected and noninfected MDMs. Stimulation of cell
proliferation by MDMs induces transient resistance to Fas-induced apoptosis.
PMID- 10195251
TI - Complete genome of a JC virus genotype type 6 from the brain of an African
American with progressive multifocal leukoencephalopathy.
AB - OBJECTIVES: The major genotypes of the human polyomavirus JC (JCV) include type 1
(European), type 2 (Asian), type 3 (African), and type 4 (United States). Here we
report characterization of the complete genome of a genotype obtained from the
brain of an African American with systemic lupus erythematosus (SLE) and
progressive multifocal leukoencephalopathy (PML). STUDY DESIGN/METHODS: DNA
extracted from JCV-infected brain tissue was subjected to whole-genome polymerase
chain reaction (PCR) amplification and direct cycle sequencing. Relations to
other JCV genotypes and the predicted amino acid sequence were analyzed. RESULTS:
This African-American type 6 strain (#601) differs from strains of all other
genotypes in about 2% of its DNA sequence. The length of the total coding region
of strain #601 is increased to 4855 bp by the insertion of a single nucleotide in
the large T-antigen intron. This strain, originally placed with the type 2 group
on the basis of its sequence in the VT-intergenic region, is very closely related
to strains recently identified in the urine of individuals from Ghana, West
Africa. CONCLUSIONS: This is the first example of an African JCV genotype
identified in the brain of an African-American PML patient. The extent of
sequence divergence of JCV type 6 suggests a split of type 6 strains before the
separation of types 2 and 3. These findings confirm that distinctive African
genotypes of JCV have been maintained in the African-American population and that
they are capable of causing PML.
PMID- 10195252
TI - Role of Kaposi's sarcoma cells in recruitment of circulating leukocytes:
implications in pathogenesis.
AB - OBJECTIVE: We sought to identify and characterize mechanisms of interaction
between Kaposi's sarcoma cells and circulating leukocytes leading to leukocyte
migration into the lesion. STUDY DESIGN/METHODS: By using static and dynamic
adhesion models, we measured the ability of late-stage KSY1 cells to support
adhesion and transmigration of peripheral blood lymphocytes (PBL). RESULTS: We
showed that resting as well as TNF-alpha- or PMA-activated KSY1 cells supported
adhesion and transmigration of PBL with a higher efficiency compared with normal
endothelial cells. The LFA1/ICAM1 pathway was totally involved in PBL adhesion to
resting or TNF-alpha-activated KSY1 cells and partially responsible for adhesion
to PMA-activated KSY1 cells. No inhibition of adhesion was observed by blockage
of the VLA4 pathway. Under flow conditions, PBL/KSY1 cell interaction was totally
dependent on L-selectin. CONCLUSION: Our data indicate that KS cells mimic an
endothelium-like structure by regulating extravasation of lymphocytes into
lesions.
PMID- 10195253
TI - Antibodies to the HIV-1 Tat protein correlated with nonprogression to AIDS: a
rationale for the use of Tat toxoid as an HIV-1 vaccine.
AB - OBJECTIVES: To investigate which immune parameters, such as antibodies against
HIV-1 specificities, or viral parameters, such as p24 antigenemia, are predictive
of disease progression. STUDY DESIGN: We performed studies on serum collected
from individuals exhibiting two extremes of disease evolution--67 fast
progressors (FP) and 182 nonprogressors (NP)--at their enrollment. After a 1- to
2-year clinical follow-up of 104 nonprogressors after their enrollment, we could
determine the best serologic predictors for disease progression. METHODS: We
investigated levels of antibodies to tetanus toxoid and to HIV antigens including
Env, Gag, Nef, and Tat proteins, as well as p24 antigenemia, viremia, CD4 cell
count, and interferon-alpha (IFN-alpha) titers in FPs and NPs, and we correlated
these data with clinical and biologic signs of progression. RESULTS: p24
Antigenemia, a marker of viral replication, and anti-Tat antibodies were highly
and inversely correlated in both groups (P < .001). Furthermore, anti-p24
antibodies and low serum IFN-alpha levels were correlated to the NP versus the FP
cohort. Finally, among NPs, only antibodies to Tat and not to the other HIV
specificities (Env, Nef, Gag) were significantly predictive of clinical stability
during their follow-up. CONCLUSION: Antibodies toward HIV-1 Tat, which are
inversely correlated to p24 antigenemia, appear as a critical marker for a lack
of disease progression. This study strongly suggests that rising anti-Tat
antibodies through active immunization may be beneficial in AIDS vaccine
development to control viral replication.
PMID- 10195254
TI - Safety and immunogenicity of HIV-1 Tat toxoid in immunocompromised HIV-1-infected
patients.
AB - OBJECTIVES: To antagonize the deleterious effects of the HIV-1 toxin
extracellular Tat on uninfected immune cells, we developed a new strategy of anti
HIV-1 vaccine using an inactivated but immunogenic Tat (Tat toxoid). Tat toxoid
has been assayed for safety and immunogenicity in seropositive patients. METHOD:
The phase I vaccine clinical trial testing Tat toxoid preparation in Seppic Isa
51 oil adjuvant was performed on 14 HIV-1-infected asymptomatic although
biologically immunocompromised individuals (500-200 CD4+ cells/mm3). RESULTS:
Following as many as 8 injections, no clinical defects were observed. All
patients exhibited an antibody (Ab) response to Tat, and some had cell-mediated
immunity (CMI) as evaluated by skin test in vivo and T-cell proliferation in
vitro. CONCLUSION: These results provide initial evidence of safety and potency
of Tat toxoid vaccination in HIV-1-infected individuals.
PMID- 10195255
TI - Prevalence of a CCR5 gene 32-bp deletion in an Israeli cohort of HIV-1-infected
and uninfected hemophilia patients.
AB - OBJECTIVE: The recently discovered connection of chemokines and their receptors
to HIV pathogenesis, and the description of the 32-bp deletion in the CCR5 gene
(delta 32 CCR5), led to heightened excitement and numerous reports regarding
their role in HIV transmission and disease progression. The populations in most
of these reports, except for one, consisted of homosexual men. Our objective was
to investigate the significance of delta 32 CCR5 in hemophilia patients in
Israel. STUDY DESIGN/METHODS: We have determined by polymerase chain reaction
(PCR) the prevalence of delta 32 CCR5 in 34 HIV-seropositive Israeli patients
with hemophilia A and compared them with a control group of 42 HIV-seronegative
hemophilia patients. RESULTS: Thirteen heterozygotes were identified among the 76
hemophilia patients tested (allelic frequency, 8.5%), 5 (14.7%) among the HIV
seropositive patients, and 8 (19%) among the noninfected. CONCLUSIONS: No
protective advantage to delta 32 CCR5 heterozygosity was seen as far as infection
with HIV is concerned. However, a trend of a slower progression to AIDS in delta
32 CCR5 heterozygotes compared with wild-type homozygotes may be apparent,
although no absolute correlation could be made.
PMID- 10195256
TI - HTLV-I serostatus of mothers of patients with adult T-cell leukemia and HTLV-I
associated myelopathy/tropical spastic paraparesis.
AB - OBJECTIVES: It has been shown that > 90% of mothers of HTLV-I-infected children
were themselves carriers of HTLV-I. This study was designed to determine the HTLV
I serostatus of mothers of patients with adult T-cell leukemia (ATL) and HTLV-I
associated myelopathy/tropical spastic paraparesis (HAM/TSP), and to assess the
association of age of exposure and disease outcome. STUDY DESIGN/METHODS: In a
cross-sectional study of the HTLV-I serostatus of mothers of HTLV-I-seropositive
patients with ATL and HAM/TSP, 36 living mothers of patients with ATL and 15
mothers of patients with TSP/HAM were traced and enrolled. RESULTS: Five of the
15 (33%) mothers of patients with HAM/TSP and 35 of the 36 (97.2%) mothers of
patients with ATL were HTLV-I-seropositive. All patients were breast-fed and none
received blood transfusions. CONCLUSION: This study confirms that infection with
HTLV-I in early childhood can lead to ATL in later life, and that HAM/TSP can
also result from early infection but more commonly results from infection
acquired in adulthood. There are several reports of posttransfusion HAM/TSP, but
ATL has not been reported following blood transfusion except in patients who were
immunocompromised. Because the newborn infant is considered to be
immunoincompetent, it seems that this is a necessary factor for the development
of ATL after infection.
PMID- 10195257
TI - Differential expression and localization of EBER-1 and EBER-2 in Epstein-Barr
virus-carrying cells.
AB - OBJECTIVE: The functions of the Epstein-Barr virus (EBV)-encoded small RNAs (EBER
1 and EBER-2) are unknown. We examined their fine intranuclear localization as
the first step to investigate their function. METHODS: We analyzed EBER-1 and
EBER-2 by in situ hybridization combined with two-color immunofluorescence
tagging. RESULTS: EBER-1 was visualized as fine dots, mainly in the euchromatin.
Ribosomal protein L-22 also formed fine dots, similar to those formed by EBER-1,
in the nuclei of EBV-carrying cells and colocalized with the latter by double
staining. EBER-2 was predominantly found in the nucleoli and was also present in
the euchromatin. The two EBERs were similarly expressed in B-cell lines of the
different phenotypes examined. The EBERs showed no colocalization by double
staining. Image analysis indicated that the level of their expression was not
correlated. CONCLUSION: The differential localization and expression of the EBER
1 and EBER-2 suggests that they may play different functional roles.
PMID- 10195258
TI - Evaluation of molecular parameters for routine assessment of viremia in patients
with chronic hepatitis C who are undergoing antiviral therapy.
AB - OBJECTIVE: To define the usefulness of molecular parameters in patients with
chronic hepatitis C who are undergoing antiviral therapy. Anti-hepatitis C virus
(HCV) treatment was monitored by determination of serum HCV load and by presence
of HCV RNA in peripheral blood mononuclear cells (PBMCs). STUDY DESIGN/METHODS:
Fifty-one patients with chronic hepatitis C undergoing antiviral therapy with
interferon-alpha plus ribavirin were studied. Serum HCV RNA load was tested with
a quantitative assay (Amplicor HCV Monitor Test) before, during, and up to 12
months after end of treatment. If HCV RNA was not detectable, serum samples were
subsequently tested with a qualitative assay (Cobas Amplicor HCV Test) and
corresponding ethylenediaminetetraacetic acid (EDTA)-treated blood was checked
for presence of HCV RNA in peripheral blood mononuclear cells (PBMCs). Sustained
virologic response was defined by loss of HCV RNA 12 months after the end of
treatment. RESULTS: Four patients (7.8%) were found to be sustained virologic
responders, 17 (33.3%) were transient virologic responders, and 30 (58.8%) were
virologic nonresponders. No significant difference was found in the median
pretreatment serum HCV RNA load between sustained virologic responders, transient
virologic responders, and virologic nonresponders. At 1 month after start of
therapy, HCV RNA was not detectable with both the serum and the PBMC assay in 12
(23.5%) of 51 patients. Four remained HCV RNA-negative until 12 months after the
end of treatment. In 14 of 17 transient virologic responders, reappearance of HCV
RNA was detected earlier in PBMCs than in serum. CONCLUSIONS: Based on these
results in 51 patients, quantitation of baseline serum HCV RNA does not appear to
be a decisive factor to the management of the individual patient. Early
assessment of serum HCV RNA level after start of anti-viral treatment seems to be
of major importance to identify virologic nonresponders. Reappearance of HCV RNA
may be demonstrated earlier in PBMCs than in serum.
PMID- 10195260
TI - Milk-borne transmission of HIV. Characterization of productively infected cells
in breast milk and interactions between milk and saliva.
AB - OBJECTIVES: Definition of the cellular constituents of breast milk and infant
saliva that are involved in milk-borne transmission of HIV infectivity. STUDY
DESIGN/METHODS: Productively infected cells in colostrum and milk of HIV-1
seropositive mothers were identified by in situ hybridization and
immunocytochemistry. Additionally, normal cells from mature milk were infected in
vitro to determine which cell types were capable of supporting productive HIV-1
infection. Cellular interactions and transfer of HIV-1 in saliva-milk mixtures
were studied to monitor the viability of milk cells and the potential for
transfer of infectious virus during ingestion of milk. RESULTS: Colostrum and
early milk from HIV-1-seropositive mothers contained 0.1% to 1% productivity
infected macrophages and T cells. Macrophages and epithelial cells from mature
milk were susceptible to productive HIV infection in vitro. When milk was mixed
with saliva, milk cells became disrupted or were bound and endocytized by
salivary epithelial cells. CONCLUSIONS: Productively infected milk cells may
contribute directly to transmission of HIV infectivity in breastfed infants
during both early and late lactation. Macrophages are the principal cellular
carriers of productive HIV-1 infection in milk. Cellular complexes produced
during milk-saliva interactions may play a key role in oral transmission of HIV.
PMID- 10195259
TI - HIV-1 nef mutations and clinical long-term nonprogression. A molecular
epidemiology study.
AB - OBJECTIVES: To analyze HIV-1 nef gene mutations in a cohort of Italian and
Swedish long-term nonprogressors (LTNP) and to investigate whether particular
amino acid substitutions are associated with LTNP. STUDY DESIGN/METHODS: nef
alleles from 21 LTNP and 8 progressor controls were amplified by polymerase chain
reaction (PCR) and sequenced. The amino acid sequences were compared with the
previously reported sequences of 16 North American LTNP and of 28 patients with
progressive infection. RESULTS: An untruncated intact open reading frame was
observed as major sequence in all LTNP and controls. None of the amino acid
substitutions in known biologically functional sites was linked to LTNP. A
valine/isoleucine at the variable position 11 was associated with both European
(P = .0001) and American (P = .001) LTNP. The interpatient nef variation was
lower among European LTNP (P = .002) than in European progressor controls.
CONCLUSIONS: Nef amino acid heterogeneity is lower among LTNP, probably
reflecting the lower HIV-1 replication rate. Nef gene defects appear uncommon in
both Swedish and Italian LTNP, although the presence of a valine/isoleucine at
position 11 is statistically associated with a lower probability to progress to
disease.
PMID- 10195261
TI - Effect of splenectomy on T-cell subsets and plasma HIV viral titers in HIV
infected patients.
AB - OBJECTIVE: In previous studies we have shown that removal of the spleen in HIV
infected people during the asymptomatic phase of disease results in slower time
to AIDS and may also result in improved survival. In this paper, we examine
whether splenectomy affects lymphocyte counts, T-cell subsets, and HIV plasma
viremia in a manner that could explain the clinical benefits associated with this
intervention. METHODS: 10 HIV-infected patients who underwent splenectomy and 23
HIV-infected controls with idiopathic thrombocytopenia purpura who did not
undergo splenectomy were studied. These groups were compared for changes in cell
subpopulations and HIV plasma viremia. RESULTS: Splenectomy resulted in increases
in absolute lymphocyte numbers with rises in both CD4 and CD8 counts, whereas CD4
and CD8 percentage levels remained unchanged. In controls, absolute and
percentage CD4+ T-cell counts declined with time from date of HIV infection.
Plasma viremia decreased more than threefold, the limit of biologic variation,
after splenectomy in 4 of 9 subjects and in only 1 of 18 controls. The proportion
of subjects exhibiting reduced viremia following splenectomy was greater than
that in HIV-infected patients that did not undergo splenectomy (chi 2 test, P =
.015). CONCLUSIONS: Improved survival and time to AIDS in splenectomized HIV
infected patients is associated with temporary reduction of plasma viremia and
increase in absolute CD4 and CD8 counts. These effects could not be attributed to
antiretroviral therapy because subjects were either untreated or treated with
antiretroviral monotherapy during the observation period. These observations may
have importance in the understanding of T-cell dynamics and the potential for
splenectomy as an HIV reservoir-debulking procedure.
PMID- 10195263
TI - State of the HIV pandemic.
PMID- 10195262
TI - Transduction of CD34+ cells by a vesicular stomach virus protein G (VSV-G)
pseudotyped HIV-1 vector. Stable gene expression in progeny cells, including
dendritic cells.
AB - OBJECTIVE: To use HIV-1 vectors to mediate stable gene transfer into
hematopoietic stem/progenitor cells. STUDY DESIGN/METHODS: Purified human CD34+
cells were transduced with HIV-1 vectors pseudotyped with VSV-G and subjected to
colony-forming assays and differentiation in liquid culture. Transduction was
determined by DNA-polymerase chain reaction (PCR) for the transgene. GFP reporter
gene expression and phenotypes of progeny cells were assessed by microscopy and
flow cytometry. RESULTS: The HIV-1 vector transduced CD34+ cells with high
efficiency. Transduction did not interfere with CD34+ cells differentiation in
vitro. Transduced genes are expressed in different subsets of progeny cells,
including those with normal dendritic cells (DC) morphology and phenotypes
(HLADR+/CD1a+/CD86+/CD14-). CONCLUSIONS: We have demonstrated efficient
transduction of hematopoietic progenitor cells by HIV-1 vectors. The transgenes
are expressed in different subsets of progeny cells, which suggests stable
integration. The generation of DCs stably expressing HIV antigens provides a new
approach for vaccine development.
PMID- 10195264
TI - Histone-mediated transfer and expression of the HIV-1 tat gene in Jurkat cells.
AB - We studied the gene transfer efficiency of lipofection reagents in comparison to
DEAE-Dextran. DOTAP, Dosper, and Lipofectin have lower transfection efficiency;
Lipofectamine has a 2.5-fold better efficiency compared with DEAE-Dextran. We
report a novel and highly efficient DNA transfer system based on the DNA-binding
proteins histone 3 and histone 4. We have transferred the HIV-1 tat gene and
measured the transactivation of HIV-1 LTR by the transactivator protein,
expressed in Jurkat cells. The HIV-1 LTR was linked to the CAT gene as a
reporter. Compared to DEAE-Dextran-mediated transfection, histone-mediated
transfection resulted in a sevenfold higher expression of the CAT gene. The
maximum transfection efficiency mediated by histones is dependent on the relative
concentration (DNA:histone ratio) and the incubation time. In a gel-retardation
assay, an optimal complex formation was observed under the same conditions that
allowed the highest transfection efficiency. This ability of histones to increase
the delivery and transgenic expression of foreign DNA in eukaryotic cells is not
simply due to the positive ionic character of the histone proteins. Polylysine,
histone H1, and histone H2A were unable to mediate gene transfection in our
system. Monoclonal antibodies that recognize antigenic determinant present on all
five histone proteins (anti-histone, pan) were able to neutralize the
transfection-enhancing potential of histone 3 and histone 4. However, anti
histone IgG enhanced the retardation of mobility of histone-DNA complexes. The
results of this study allow us to conclude that histones H3 and H4 can catalyze
gene transfer and gene expression in eukaryotic cells without any requirement for
additional constituents. For this reason, we have termed the new gene-delivery
system as histonefection.
PMID- 10195265
TI - Involvement of protein-DNA interaction in adeno-associated virus Rep78-mediated
inhibition of HIV-1.
AB - OBJECTIVE: It has been well documented by several laboratories that adeno
associated virus (AAV) is able to inhibit HIV-1 replication and gene expression.
This effect has been mapped to the AAV-encoded Rep78 protein. However, the
mechanism by which Rep78 is able to inhibit HIV-1 is unclear. As Rep78 is a DNA
binding transcription factor, the objective of this study was to investigate
where Rep78 might bind within the HIV-1 long terminal repeat (LTR) sequences and
to judge the importance of this protein-DNA interaction. STUDY DESIGN/METHODS:
Rep78's binding to HIV-LTR DNA was analyzed by electrophoretic mobility shift
assay (EMSA). The importance of this protein-DNA interaction was analyzed using a
Rep78 mutant defective for binding HIV-LTR DNA in an assay for monitoring gene
expression (chloramphenicol acetyltransferase [CAT] assay). RESULTS: The
preferred site for Rep78 binding was found to be adjacent to the HIV-LTR TATA
box, within nt -54 to -34 relative to the site of transcription initiation.
Furthermore, a Rep78 mutant with substitutions at amino acid residues 64 and 65
which was found defective for binding HIV-LTR DNA, was also found to be defective
for inhibition of tat transactivated HIV-LTR gene expression. CONCLUSION: These
data strongly suggest that Rep78's DNA binding ability is important for its
mechanism of inhibition. Furthermore, the TATA box region of the HIV-LTR, to
which Rep78 preferentially binds, is a likely target through which the inhibition
takes place.
PMID- 10195266
TI - Fast genotypic detection of drug resistance mutations in the HIV-1 reverse
transcriptase gene of treatment-naive patients.
AB - OBJECTIVES: This study was performed to assess the frequency of drug resistance
mutations in treatment-naive HIV-1-infected patients. STUDY DESIGN/METHODS:
Frozen plasma samples from 135 treatment-naive HIV-infected adults were available
from the first time the patients were seen for their infection in our center
between 1992 and 1997. A rapid genotypic assay based on reverse DNA hybridization
(LiPA HIV-1 RT, Murex, London, U.K.) was used to study substitutions at reverse
transcriptase (RT) codons 41, 69, 70, 74, 184, and 215. Additionally, a selective
polymerase chain reaction (PCR) for the multiple dideoxynucleoside resistance
(MddNR) mutation Q151M was performed. RESULTS: 16 patients (12%) harbored virus
with one or more drug resistance mutations. The prevalence of patients with drug
resistant virus was 0% in 1992, 17% in 1993, 0% in 1994 (only 6 samples tested),
18% in 1995, 14% in 1996, and 9% in 1997. Mutation K70R (resistance to
zidovudine) was found in 8 patients, M41L (resistance to zidovudine) in 5
patients, M184V/I (resistance to ddI/ddC/3TC) in 2 patients, and T215Y/F
(resistance to zidovudine) in 4 patients. All samples were wild type at codons 69
(ddC), 74 (ddI), and 151 (MddNR). CONCLUSIONS: Virus strains containing drug
resistance mutations are now found in about 1 of 10 treatment-naive HIV-1
seropositive patients in Luxembourg. We believe that testing for drug-resistant
virus before starting treatment should be recommended and will help to improve
the selection of the most effective antiretroviral treatment. We also suggest the
need for an international surveillance program on HIV drug resistance in
treatment-naive patients.
PMID- 10195268
TI - Role of the CCR5 delta 32 allele in resistance to HIV-1 infection in west Africa.
AB - OBJECTIVE: To determine the frequency of the mutant CCR5 delta 32 allele in high
risk HIV-seronegative Africans as compared with the general African population,
and to assess its in vitro protective efficacy against HIV-1 infection. STUDY
DESIGN: In the homozygous form, the CCR5 delta 32 allele confers resistance to
macrophage-tropic (M-tropic) strains of HIV-1. Assuming that genetic
characteristics favoring HIV resistance would prevail in a high-risk HIV
seronegative population, we examined the CCR5 genotypes of female commercial sex
workers (CSWs) from Dakar, Senegal, who have remained uninfected for an elongated
period. METHODS: The CCR5 genetic profile of study participants was determined by
polymerase chain reaction (PCR) amplification of genomic DNA followed by
sequencing. Peripheral blood mononuclear cells (PBMCs) were infected with
different strains of HIV-1 and monitored by p24 enzyme-linked immunosorbent assay
(ELISA). RESULTS: We confirmed the presence of two CCR5wt/delta 32 genotypes
among 139 individuals (1.44%). PBMCs from these 2 heterozygous individuals were
also found to be less susceptible to in vitro infection by an M-tropic HIV-1
primary isolate. CONCLUSIONS: Evidence was found of an increased prevalence of
the CCR5wt/delta 32 genotype in a high-risk HIV-seronegative cohort in West
Africa. Furthermore, reduced susceptibility to HIV-1 infection among heterozygous
individuals supports a role for 32-bp CCR5 deletion in HIV-1 resistance.
PMID- 10195267
TI - Low peripheral blood viral HIV-2 RNA in individuals with high CD4 percentage
differentiates HIV-2 from HIV-1 infection.
AB - OBJECTIVES: To elucidate why the virulence of HIV-1 and HIV-2 infections differ
in West African populations. STUDY DESIGN/METHOD: Peripheral blood plasma virion
RNA and cellular proviral DNA levels were measured in a cross-section of 59 HIV-1
and 49 HIV-2 singly infected individuals representing all stages of infection in
The Gambia, West Africa. Novel reverse transcriptase polymerase chain reaction
(RT-PCR) assays specific and sensitive for virus quantification of non-clade B
HIV-1 and HIV-2 infections were used. RESULTS: HIV-1 and HIV-2 proviral and
plasma RNA levels were inversely correlated with CD4+ count for both infections
with cellular proviral load similar at each stage of infection. Critically, up to
three-fourths of HIV-2-infected individuals with high CD4 percentages (> 28%) had
undetectable (< 500 copies/mL) levels of peripheral blood HIV-2 RNA in contrast
to HIV-1-infected individuals who had readily detectable plasma virus at all
stages of infection (P < .0001). Plasma RNA levels were similar in the
intermediate and end stages of infection, indicating similar replication
potential for both viruses. In the cross-section of HIV-1- and HIV-2-infected
patients studied, the data indicate a wider dynamic range of HIV-2 RNA in vivo
compared with HIV-1. DISCUSSION: Low levels of HIV-2 replication and virion
expression characterize individuals with high CD4+ lymphocyte counts, suggesting
that a very different dynamic equilibrium exists between virus and host for HIV-2
compared with HIV-1. By analogy with HIV-1, our data implicate a considerably
lower turnover of HIV-2 virion RNA in vivo with a markedly reduced production of
infectious genomes in individuals during the subclinical phase of infection.
CONCLUSION: The lower levels of virion expression of HIV-2 infections in vivo are
compatible with observed differences in the natural history of HIV-1 and HIV-2
infections, relating to overall differences in the pathogenesis and disease
progression of the two infections.
PMID- 10195269
TI - Lymphoblastoid cell lines with integrated human herpesvirus type 6.
AB - OBJECTIVE: Attempts were made to establish stable in vitro cell lines latently
infected with human herpesvirus type 6 (HHV-6). STUDY DESIGN/METHODS: We
previously studied a patient with B-cell acute lymphoblastic leukemia infected
with HHV-6. The peripheral blood mononuclear cells (PBMCs) from this patient were
immortalized by infection with Epstein-Barr virus (EBV) and herpesvirus saimiri
(HVS). RESULTS: Infection of the PBMCs with EBV and HVS gave rise to B- and T
lymphoblastoid cell lines, respectively. Both cell lines were positive for HHV-6
DNA, as confirmed by polymerase chain reaction (PCR) and Southern blot
hybridization. Fluorescence in situ hybridization (FISH) demonstrated integration
of HHV-6 in these cell lines. Only one integrated site of viral DNA was detected
in metaphase chromosome spreads, and it was preferentially located at the long
arm of chromosome 1 (1q44). HHV-6 appeared latent in the infected cells, since
neither the HHV-6 immediate-early gene transcript nor virion-associated protein
was detected. CONCLUSIONS: The HHV-6-positive lymphoblastoid cell lines would be
useful for study of the mechanism of HHV-6 integration.
PMID- 10195270
TI - Chamber testing of adsorption of volatile organic compounds (VOCs) on material
surfaces.
AB - A simple test chamber method to quantify adsorption and desorption of organic
compounds on material surfaces is described. Important environmental parameters
such as temperature, relative humidity and air velocity were varied and
controlled independently around typical indoor values. Experiments were performed
with alpha-pinene and toluene in concentrations of 160-300 micrograms/m3. The
measurements show adsorption on and desorption from wool carpet, nylon carpet,
polyvinyl chloride (PVC) floor coverings, cotton curtain material and the empty
chamber. The ranking of the materials, with respect to their sorption capacity,
is as mentioned above. The adsorption of alpha-pinene was higher than the
adsorption of toluene for all the materials. Air velocity was not found to
influence the sorption of alpha-pinene and toluene on wool carpet, tested with
air velocities at 0, 10 and 20 cm/s. The experiments were carried out during both
the adsorption and the desorption phase. The uncertainty of the experiments was
lowest during the desorption phase. Based on the results obtained, it can be
recommended that sorption experiments should be performed as desorption phase
experiments. A one-sink model, based on the Langmuir adsorption isotherm, appears
adequate to describe the results.
PMID- 10195271
TI - Volatile organic compound emissions from latex paint--Part 1. Chamber experiments
and source model development.
AB - Latex paints are widely used in residential and commercial indoor environments.
The surface areas covered by the paints in these environments are relatively
large. Thus, latex paints have the potential for having a major impact on indoor
air quality (IAQ). A study was undertaken to develop methods for evaluating the
impact of latex paint emission on IAQ. Small chamber experiments using stainless
steel and painted and unpainted gypsum board substrates were conducted to
determine the emission characteristics of latex paint. The emissions from the
stainless steel were relatively short lived (3 to 4 days), whereas the emissions
from gypsum board lasted for over 200 days. Because gypsum board is a common
substrate for latex paint, all emission models were developed for the gypsum
board substrates. The data from the small chamber tests led to the development of
two empirical and two mass-transfer-based source emission models. Approximately
100 to 200 days of data were required to estimate the parameters required for the
empirical models. Only 8 days of data were required to estimate the parameters
for the mass-transfer-based models. The final models use paint formulation and
mass transfer correlations to predict the emissions of the major individual
volatile organic compounds emitted by latex paint.
PMID- 10195272
TI - Volatile organic compound emissions from latex paint--Part 2. Test house studies
and indoor air quality (IAQ) modeling.
AB - Emission models developed using small chamber data were combined with an Indoor
Air Quality (IAQ) model to analyze the impact of volatile organic compound (VOC)
emissions from latex paint on indoor environments. Test house experiments were
conducted to verify the IAQ model's predictions. The agreement between model
predictions and experimental measurements met the American Society for Testing
and Materials criteria for model verification in the room with the source and met
most of the requirements in other rooms. The major cause of disagreement between
the model predictions and the experimental data in the test house appears to be
an inadequate sink model.
PMID- 10195273
TI - Reproducibility of indoor environment characteristics obtained in a walk through
questionnaire. A pilot study.
AB - Walk through questionnaires may be feasible tools to obtain data on the indoor
environment in community studies. However, limited information is available
regarding the reproducibility of the data obtained through these questionnaires.
In this pilot study, two construction engineering students inspected ten
dwellings twice by means of a standardized walk through questionnaire. The two
engineering students inspected the dwellings independent of each other within two
months. Time between the two visits varied between 14 and 40 days. The variables
presented were based on information from the residents and inspection. The
continuous variables recorded included number of rooms in the dwellings, room
volume, length of filled shelves and textile area. The inter- and intra-observed
variabilities were poorer for number of rooms and shelf factor than for the other
variables. For the 3 of the 9 categorical variables based on inspection, the
inter-observer comparison showed complete agreement with a kappa statistics of
1.0, these variables being condition of the window frames and construction of
outside walls and roof. One of the categorical variables showed a kappa
statistics of < 0.5, these variables being presence of basement and presence of
condensation at windows. This study indicates a wide variation in observer
variability between various items of a walk through questionnaire. Clear
definitions of all the parts of the questionnaire are needed, as well as thorough
training of observers.
PMID- 10195274
TI - Microanalysis of indoor aerosols and the impact of a compact high-efficiency
particulate air (HEPA) filter system.
AB - Aerosol particles in municipal atmospheres are of increasing public health
concern; however, since most of our time is spent indoors, indoor aerosols must
be researched in counterpart. Compact High-Efficiency Particulate Air (HEPA)
filter systems are commonly employed in residences to alleviate airborne dust
concentrations. In this study, a detailed and original methodology was used to
determine concentrations and types of submicrometer aerosols, as well as of large
(> 4 microns) dust particles. Scanning electron microscopy was used to quantify
and characterize ambient aerosols collected from filtered and non-filtered rooms.
Particle concentrations were significantly lower in samples collected in the
presence of the filter system (mean 23 to 8 coarse particles liter-1, 63%
reduction; 13 to 3 inorganic submicron particles cm-3, 76% reduction; 85 to 33
total submicron particles cm-3, 62% reduction; all P < 0.05). This study provides
a new methodology for analysis of indoor aerosols and new data on their physico
chemical characteristics. Since the filter systems are effective at reducing
submicron aerosol concentrations, they may improve the health of individuals such
as asthmatics, who experience health problems caused by anthropogenic fine
particles.
PMID- 10195275
TI - Measurements of biological contaminants and particulate matter inside a dwelling
in Japan.
AB - To investigate the biological contaminant levels inside dwellings in Japan, the
authors measured fungal indices, airborne mite allergens (Der 1 and Der 2), and
suspended particulate matter (SPM). Measurements were continuously conducted at
one dwelling located in Yokosuka-city, Kanagawa. The biosensors for fungal index
were set at 12 points inside and 2 points outside the dwelling. An SPM sampler
was placed in the living room, and samplers for collecting allergens were placed
in the living room and in the washroom. The peak level of the fungal index was
recorded during July, which is the rainy season in Japan. The highest value in
the dwelling was 6.9 in the toilet, and the second highest was 6.6 near a window
in the living room that faces southeast, and behind the sofa. The highest monthly
SPM level was 21.5 micrograms/m3 during October, and the highest monthly allergen
level (Der 1) in the living room was 25.7 pg/m3 during November. A positive
relationship between the fungal index and mite allergens was not observed, and
the levels of contaminants were not as those found in other studies. However,
further study to investigate the distribution of biological contaminants is
needed because indoor temperature and relative humidity are comparatively high.
PMID- 10195276
TI - Air-change effectiveness: theory and calculation methods.
AB - This paper reports the development of methods for calculating a ventilation
performance metric that is a measure of the airflow pattern in a room or zone of
a multi-zone ventilation system. Temporal mixing theory is used as the basis for
these methods. The methods are applicable to all ventilated systems that can be
modeled as a set of interconnected chambers. Relations between the ventilation
performance metric defined in this paper and those defined previously are
derived. The theoretical results of this paper are consistent with published
experimental findings. They also illustrate that the conclusions in some
experimental studies about the airflow patterns in working buildings may be
incorrect. Re-analysis of previously published data illustrates how common
features of mechanically ventilated buildings, such as recirculation of return
air and multiple chambers, confound information about airflow patterns in tracer
gas data. The calculation methods developed in this paper can be used to undo
this confounding.
PMID- 10195277
TI - Evaluating age from arbitrary forms of injection functions of tracer.
AB - The age of the air in a room is normally determined either from a pulse response
or from a step change response (up or down). There are a certain number of
problems involved in applying these two theoretical models, especially those
associated with the duration of the injection, which must either be infinitely
short or infinitely long. A hybrid method that consists of injecting a known
quantity of tracer for a given time offers the advantages of both methods. The
equation for calculating age is exact, regardless of the type of flow considered,
and is derived from the expressions already established for a pulse response to
which a correction is included to account for the tracer generation function. If
a rectangular pulse is used for the injection, the solution is particularly
simple.
PMID- 10195278
TI - Influence of the boundary thermal conditions on the air change efficiency
indexes.
AB - The influence of a thermal heterogeneity boundary conditions on the air change
efficiency (ACE) of a mechanical ventilation system in a test room was
experimentally evaluated by means of the "step-down" tracer gas technique in 24
different experimental conditions. The experiments were performed under
isothermal condition, varying the air supply temperature with respect to the
walls and varying the surface temperature of a wall with respect to the other
walls and the supply air, simulating both heating and cooling situations.
Changing the position of the outlet grid two different configurations of the
ventilation system were tested. The nominal supply air velocity varied between
0.04 and 0.11 m/s, corresponding to a range from 1 to 3 ach, and the temperature
differences varied from 0 to 5 degrees C. Results are reported in terms of air
change efficiency indexes, both local and global. The global air change
efficiency (ACE), values are presented as a function of the Archimedes number
(Ar), whose values were in the range 0 to 181. The reported results suggest that
the Ar number may be used to organize the ACE values when in the presence of
thermal heterogeneity, both in the external envelope and in the supplied air. The
obtained results show that there is a logarithmic relation between Ar and ACE. In
particular, for both ventilation strategies tested, the increase of the absolute
value of Ar leads to an increase of ACE when the supply air is warmer than the
walls, and to a decrease of ACE when the supply air is colder than the walls.
Under isothermal conditions the Reynolds number (Re) fairly correlates the
experimental results.
PMID- 10195279
TI - Twilight zone of protein sequence alignments.
AB - Sequence alignments unambiguously distinguish between protein pairs of similar
and non-similar structure when the pairwise sequence identity is high (>40% for
long alignments). The signal gets blurred in the twilight zone of 20-35% sequence
identity. Here, more than a million sequence alignments were analysed between
protein pairs of known structures to re-define a line distinguishing between true
and false positives for low levels of similarity. Four results stood out. (i) The
transition from the safe zone of sequence alignment into the twilight zone is
described by an explosion of false negatives. More than 95% of all pairs detected
in the twilight zone had different structures. More precisely, above a cut-off
roughly corresponding to 30% sequence identity, 90% of the pairs were homologous;
below 25% less than 10% were. (ii) Whether or not sequence homology implied
structural identity depended crucially on the alignment length. For example, if
10 residues were similar in an alignment of length 16 (>60%), structural
similarity could not be inferred. (iii) The 'more similar than identical' rule
(discarding all pairs for which percentage similarity was lower than percentage
identity) reduced false positives significantly. (iv) Using intermediate
sequences for finding links between more distant families was almost as
successful: pairs were predicted to be homologous when the respective sequence
families had proteins in common. All findings are applicable to automatic
database searches.
PMID- 10195280
TI - Combining sensitive database searches with multiple intermediates to detect
distant homologues.
AB - Using data from the CATH structure classification, we have assessed the blastp,
fasta, smith-waterman and gapped-blast algorithms, developed a portable
normalization scheme and identified safe thresholds for database searching. Of
the four methods assessed, fasta, smith-waterman and gapped-blast perform
similarly, whereas the sensitivity of blastp was much lower. Introduction of an
intermediate sequence search substantially improved the results. When tested on a
set of relationships that could not be identified by blastp, intermediate
sequences were able to find double the number of relationships identified by the
smith-waterman algorithm alone. However, we found that the benefit of using
intermediates varied considerably between each family and depended not only on
the number of available sequences, but also their diversity. In an attempt to
increase sensitivity further, a multiple intermediate sequence search (MISS)
procedure was developed. When assessed on 1906 cases from a wide range of
homologous families that could not be detected by the previous approaches, MISS
was able to identify 241 additional relationships. MISS uses the full extent of
sequence diversity to detect additional relationships, but does not consider any
structure-specific information. For this reason, it is more generally applicable
than fold recognition and threading methods, which require a library of known
structures.
PMID- 10195281
TI - Spatial sign-alternating charge clusters in globular proteins.
AB - Large sign-alternating charge clusters formed by the charged side groups of amino
acid residues and N- and C-terminal groups were found in the majority of
considered globular proteins, namely 235 in a total of 274 protein structures,
i.e. 85.8%. The clusters were determined by the criteria proposed earlier:
charged groups were included in the cluster if their charged N and O atoms were
located at distances between 2.4 and 7.0 A. The set of selected proteins
consisted of known non-homologous protein structures from the Protein Data Bank
with a resolution less than or equal to 2.5 A and pair sequence similarity less
than 25%. Molecular masses of the proteins were from 5.5 to 91.5 kDa and protein
chain length from 50 to 830 residues. The distribution of charged groups on the
protein surface between isolated charged groups, small clusters with two and
three groups, and large clusters with four or more groups were found to be
approximately similar making 33, 35 and 32% of the total amount of protein
charged groups, respectively. The large sign-alternating charge clusters with
four or more charged groups were studied in greater detail. The amount of such
clusters depends on the protein chain length. The small proteins contain 1-3
clusters while the large proteins display 4-6 or more clusters. On average, 1.5
clusters per each 100 residues were observed. In contrast with this, the size of
a cluster, i.e. the number of charged groups inside a cluster, does not depend on
the protein molecular mass, and large clusters are observed for proteins from a
range of molecular masses. Clusters consisting of four to six charged groups
occur most frequently, although extra large clusters are also often revealed. We
can conclude that sign-alternating charge clusters are a common feature of the
protein surface of globular protein. They are suggested to play a general
functional role as a local polar factor of protein surface.
PMID- 10195282
TI - Protein subcellular location prediction.
AB - The function of a protein is closely correlated with its subcellular location.
With the rapid increase in new protein sequences entering into data banks, we are
confronted with a challenge: is it possible to utilize a bioinformatic approach
to help expedite the determination of protein subcellular locations? To explore
this problem, proteins were classified, according to their subcellular locations,
into the following 12 groups: (1) chloroplast, (2) cytoplasm, (3) cytoskeleton,
(4) endoplasmic reticulum, (5) extracell, (6) Golgi apparatus, (7) lysosome, (8)
mitochondria, (9) nucleus, (10) peroxisome, (11) plasma membrane and (12)
vacuole. Based on the classification scheme that has covered almost all the
organelles and subcellular compartments in an animal or plant cell, a covariant
discriminant algorithm was proposed to predict the subcellular location of a
query protein according to its amino acid composition. Results obtained through
self-consistency, jackknife and independent dataset tests indicated that the
rates of correct prediction by the current algorithm are significantly higher
than those by the existing methods. It is anticipated that the classification
scheme and concept and also the prediction algorithm can expedite the
functionality determination of new proteins, which can also be of use in the
prioritization of genes and proteins identified by genomic efforts as potential
molecular targets for drug design.
PMID- 10195283
TI - Structural interpretation of site-directed mutagenesis and specificity of the
catalytic subunit of protein kinase CK2 using comparative modelling.
AB - The catalytic subunit of protein kinase casein kinase 2 (CK2alpha), which has
specificity for both ATP and GTP, shows significant amino acid sequence
similarity to the cyclin-dependent kinase 2 (CDK2). We constructed site-directed
mutants of CK2alpha and used a three-dimensional model to investigate the basis
for the dual specificity. Introduction of Phe and Gly at positions 50 and 51, in
order to restore the pattern of the glycine-rich motif, did not seriously affect
the specificity for ATP or GTP. We show that the dual specificity probably
originates from the loop situated around the position His115 to Asp120 (HVNNTD).
The insertion of a residue in this loop in CK2 alpha subunits, compared with CDK2
and other kinases, might orient the backbone to interact with the base A and G;
this insertion is conserved in all known CK2alpha. The mutant deltaN118, the
design of which was based on the modelling, showed reduced affinity for GTP as
predicted from the model. Other mutants were intended to probe the integrity of
the catalytic loop, alter the polarity of a buried residue and explore the
importance of the carboxy terminus. Introduction of Arg to replace Asn189, which
is mapped on the activation loop, results in a mutant with decreased k(cat),
possibly as a result of disruption of the interaction between this residue and
basic residues in the vicinity. Truncation at position 331 eliminates the last 60
residues of the alpha subunit and this mutant has a reduced catalytic efficiency
compared with the wild-type. Catalytic efficiency is restored in the truncation
mutant by the replacement of a potentially buried Glu at position 252 by Lys,
probably owing to a higher stability resulting from the formation of a salt
bridge between Lys252 and Asp208.
PMID- 10195284
TI - Molecular dynamics simulation of alpha-lactalbumin and calcium binding c-type
lysozyme.
AB - Alpha-lactalbumins (LAs) and c-type lysozymes (LYZs) are two classes of proteins
which have a 35-40% sequence homology and share a common three dimensional fold
but perform different functions. Lysozymes bind and cleave the glycosidic bond
linkage in sugars, where as, alpha-lactalbumin does not bind sugar but
participates in the synthesis of lactose. Alpha-lactalbumin is a metallo-protein
and binds calcium, where as, only a few of the LYZs bind calcium. These proteins
consist of two domains, an alpha-helical and a beta-strand domain, separated by a
cleft. Calcium is bound at a loop situated at the bottom of the cleft and is
important for the structural integrity of the protein. Calcium is an ubiquitous
intracellular signal in higher eukaryotes and structural changes induced on
calcium binding have been observed in a number of proteins. In the present study,
molecular dynamics simulations of equine LYZ and human LA, with and without
calcium, were carried out. We detail the differences in the dynamics of equine
LYZ and human LA, and discuss it in the light of experimental data already
available and relate it to the behavior of the functionally important regions of
both the proteins. These simulations bring out the role of calcium in the
conformation and dynamics of these metallo-proteins. In the calcium bound LA, the
region of the protein around the calcium binding site is not only frozen but the
atomic fluctuations are found to increase away from the binding site and peak at
the exposed sites of the protein. This channeling of fluctuations away from the
metal binding site could serve as a general mechanism by which the effect of
metal binding at a site is transduced to other parts of the protein and could
play a key role in protein-ligand and/or protein-protein interaction.
PMID- 10195285
TI - A three-dimensional construction of the active site (region 507-749) of human
neutral endopeptidase (EC.3.4.24.11).
AB - A three-dimensional model of the 507-749 region of neutral endopeptidase-24.11
(NEP; E.C.3.4.24.11) was constructed integrating the results of secondary
structure predictions and sequence homologies with the bacterial endopeptidase
thermolysin. Additional data were extracted from the structure of two other
metalloproteases, astacin and stromelysin. The resulting model accounts for the
main biological properties of NEP and has been used to describe the environment
close to the zinc atom defining the catalytic site. The analysis of several thiol
inhibitors, complexed in the model active site, revealed the presence of a large
hydrophobic pocket at the S1' subsite level. This is supported by the nature of
the constitutive amino acids. The computed energies of bound inhibitors
correspond with the relative affinities of the stereoisomers of benzofused
macrocycle derivatives of thiorphan. The model could be used to facilitate the
design of new NEP inhibitors, as illustrated in the paper.
PMID- 10195286
TI - Homogenization and crystallization of histidine ammonia-lyase by exchange of a
surface cysteine residue.
AB - Histidase (histidine ammonia-lyase, EC 4.3.1.3) from Pseudomonas putida was
expressed in Escherichia coli and purified. In the absence of thiols the
tetrameric enzyme gave rise to undefined aggregates and suitable crystals could
not be obtained. The solvent accessibility along the chain was predicted from the
amino acid sequence. Among the seven cysteines, only one was labeled as 'solvent
exposed'. The exchange of this cysteine to alanine abolished all undefined
aggregations and yielded readily crystals diffracting to 1.8 A resolution.
PMID- 10195287
TI - Mutation of a highly conserved aspartate residue in subdomain IX abolishes Fer
protein-tyrosine kinase activity.
AB - Before the structure of cAMP-dependent protein kinase had been solved, sequence
alignments had already suggested that several highly conserved peptide motifs
described as kinase subdomains I through XI might play some functional role in
catalysis. Crystal structures of several members of the protein kinase
superfamily have suggested that the nearly invariant aspartate residue within
subdomain IX contributes to the conformational stability of the catalytic loop by
forming hydrogen bonds with backbone amides within subdomain VI. However,
substitution of this aspartate with alanine or threonine in some protein kinases
have indicated that these interactions are not essential for activity. In
contrast, we show here that conversion of this aspartate to arginine abolished
the catalytic activity of the Fer protein-tyrosine kinase when expressed either
in mammalian cells or in bacteria. Structural modeling predicted that the
catalytic loop of the FerD743R mutant was disrupted by van der Waal's repulsion
between the side chains of the substituted arginine residue in subdomain IX and
histidine-683 in subdomain VI. The FerD743R mutant model predicted a shift in the
peptide backbone of the catalytic loop, and an outward rotation of histidine-683
and arginine-684 side chains. However, the position and orientation of the
presumptive catalytic base, aspartate-685, was not substantially changed. The
proposed model explains how substitutions of some, but not all residues could be
tolerated at this nearly invariant aspartate in kinase subdomain IX.
PMID- 10195288
TI - Mutations to alter Aspergillus awamori glucoamylase selectivity. IV. Combinations
of Asn20-->Cys/Ala27-->Cys, Ser30-->Pro, Gly137-->Ala, 311-4 loop, Ser411-->Ala
and Ser436-->Pro.
AB - Six previously constructed and nine newly constructed Aspergillus awamori
glucoamylases with multiple mutations made by combining existing single mutations
were tested for their ability to produce glucose from maltodextrins. Multiple
mutations have cumulative effects on glucose yield, specific activity and
thermostability. No general correlation between glucose yield and thermostability
was observed, although mutations that presumably impede unfolding at high
temperatures uniformly increase thermostability and generally increase glucose
yield. Peak glucose yields decrease with increasing temperature. The best
combination of high glucose yield, high specific activity and high
thermostability occurs in Asn20-->Cys/Ala27-->Cys/Ser30-->Pro/Gly137-->Ala
glucoamylase.
PMID- 10195289
TI - Hydrophobicity engineering of cholera toxin A1 subunit in the strong adjuvant
fusion protein CTA1-DD.
AB - Protein engineering of the cholera toxin A1 subunit (CTA1) fused to a dimer of
the Ig-binding D-region of Staphylococcus aureus protein A (DD) was employed to
investigate the effect of specific amino acid changes on solubility, stability,
enzymatic activity and capacity to act as an adjuvant in vivo. A series of CTA1
DD analogues were selected by a rational modeling approach, in which surface
exposed hydrophobic amino acids of CTA1 were exchanged for hydrophilic
counterparts modeled for best structural fit. Of six different mutants initially
produced, two analogues, CTA1Phe132Ser-DD and CTA1Pro185Gln-DD, were demonstrated
to have 50 and 70% increased solubility, respectively, at neutral pH. The double
mutant CTA1Phe132Ser/Pro185Gln-DD was at least threefold more soluble,
demonstrating an additive effect of the two mutations. Only the Phe132Ser
analogue retained full biological activity and stability compared with the native
CTA1-DD fusion protein. Two mutants, Pro185Gln and Phe31His mutations, exhibited
unaltered ADP-ribosyltransferase activity in vitro, but demonstrated markedly
reduced adjuvant function. Since the Pro185 and Phe31 amino acids are located in
close vicinity on the distal side of the molecule relative to the enzymatically
active cleft, it is conceivable that this region is involved in mediating a
biological function, separate from the enzymatic activity but intrinsic to the
adjuvant activity of CTA1.
PMID- 10195290
TI - Efficient site specific removal of a C-terminal FLAG fusion from a Fab' using
copper(II) ion catalysed protein cleavage.
AB - The peptide sequence (N)DKTH(C) was investigated as a site for efficient,
specific cleavage of a fusion protein by cupric ions using a humanised gamma1
Fab' as a model protein. The native upper hinge (N)DKTH(C) sequence was mutated
to create a site resistant to cleavage by cupric ions and a (N)DKTH(C) sequence
introduced between the hinge and a C-terminal FLAG peptide. Incubation of Fab'
with Cu2+ at 62 degrees C at alkaline pHs resulted in removal of the FLAG peptide
with efficiencies of up to 86%. Cleavage conditions did not detrimentally affect
the Fab' protein. Use of the (N)DKTH(C) sequence along with cupric ions may
provide a cost-effective method for large scale proteolytic cleavage of fusion
proteins.
PMID- 10195291
TI - Intermediate to long-term follow-up of medial-approach dorsal cheilectomy for
hallux rigidus.
AB - Dorsal cheilectomy of the hallux metatarsophalangeal (MTP) joint through a medial
approach can effectively provide long-term relief of pain and improve function in
symptomatic mild-to-moderate hallux rigidus, despite progression of generalized
first MTP joint arthritic degeneration and/or loss of motion. Fifty-seven
patients (75 feet) with arthritis of the first MTP joint underwent dorsal
cheilectomy through a medial approach for hallux rigidus failing nonoperative
management. Excision of the dorsal articular surface of the first metatarsal head
and dorsal osteophytes was performed through a medial approach that also allowed
for plantar capsular release and removal of lateral osteophytes. Minimum follow
up was 3 years (average, 63 months; range, 37-92 months). Fifty-two patients (68
feet) returned for clinical and radiographic evaluation. American Orthopaedic
Foot and Ankle Society Hallux Rating scores improved from a preoperative average
of 45 to 85 points at follow-up. Average dorsiflexion improved from 19 degrees to
39 degrees, and the average range of motion improved from 34 degrees to 64
degrees. Preoperative radiographic grade of arthritic degeneration was grade I in
17 feet, grade II in 39 feet, and grade III in 12 feet; at follow-up, the
radiographic grade was grade I in 2 feet, grade II in 26 feet, and grade III in
40 feet. Thirty-two feet worsened one grade, 6 feet worsened two grades, and 28
feet demonstrated no change (12 of 28 were grade III, preoperatively). A dorsal
spur recurred in 21 feet, 9 of which were symptomatic. Complications included two
superficial wound infections and four transient paresthesias of the hallux, all
of which resolved uneventfully.
PMID- 10195292
TI - Morton's metatarsalgia: sonographic findings and correlated histopathology.
AB - The results of 79 high resolution ultrasound examinations of the forefoot that
were performed for suspected Morton's metatarsalgia were retrospectively
assessed. Scans were only obtained if the pain was poorly localized or if there
were atypical features that made the clinical diagnosis uncertain. Ultrasound
detected 92 hypoechoic intermetatarsal web space masses in 63 patients. Surgery
was performed on 23 web spaces in 22 patients where the response to nonsurgical
management had been poor. The surgical specimens were retrieved and reviewed by a
pathologist in 21 cases. The histopathology in 20 of 21 operated cases was that
of Morton's neuroma; however, prominent mucoid degeneration was also found to
involve the adjacent loose fibroadipose tissues in 19 of 20 neuroma specimens.
Ultrasound was sensitive in the detection of web space abnormality (sensitivity,
0.95), but could not clearly separate Morton's neuroma from associated mass-like
mucoid degeneration in the adjacent loose connective tissues. The implications of
these observations for both diagnosis and treatment are discussed.
PMID- 10195293
TI - Comparison of open isolated subtalar arthrodesis with autogenous bone graft
versus outpatient arthroscopic subtalar arthrodesis using injectable bone
morphogenic protein-enhanced graft.
AB - Isolated subtalar joint arthrodesis is an established salvage procedure that can
be performed in various ways for varying diagnoses. The purpose of this article
is to report a new arthroscopic subtalar arthrodesis technique that has been
developed. The results of this method versus an open technique were compared.
Length of hospital stay, tourniquet time, morbidity, and fusion rate were studied
in 17 fusion patients between 1990 and 1997. Twelve patients had open arthrodesis
with bone graft and 5 patients had arthroscopic arthrodesis with supplemental,
injectable, osteoinductive enhanced-graft gel. The length of stay decreased 1.7
days with the arthroscopic procedure. Tourniquet time was not significantly
different. One open procedure required refusion, whereas none did in the
arthroscopic group. One patient in each group required AO screw removal. In
selected patients with subtalar arthrosis without significant hindfoot deformity,
arthroscopic arthrodesis can be an effective. It is too early to determine if
there are specific advantages in this procedure compared with a conventional open
arthrodesis.
PMID- 10195294
TI - Subtalar arthrodesis for late sequelae of calcaneal fractures: fusion in situ
versus fusion with sliding corrective osteotomy.
AB - Primary subtalar arthritis is not common. In most cases, it is the late sequela
of intra-articular calcaneal fracture. Subtalar arthrodesis is mostly used for
the treatment of traumatic subtalar arthritis in our clinics. We have compared
our early cases of in-situ subtalar fusion with our recent cases of fusion with
sliding corrective osteotomy in this clinical report. From 1989 to 1992, 15 feet
of 13 patients were treated with subtalar arthrodeses for subtalar arthritis
caused by malunion of calcaneal fractures. Fusion in situ was done by Ollier's
approach, and resection of bony protrusion was done if there was lateral
entrapment syndrome. From 1992 to 1995, 13 feet of 12 patients also received
subtalar arthrodeses to salvage their calcaneal fractures, but the subtalar
fusion was done by wide lateral approach, calcaneal sliding corrective osteotomy,
and sometimes (11 of 13 feet) with Achilles tendon lengthening to restore the
calcaneal height and width. Patients of both groups experienced obvious clinical
improvement in subtalar pain relief, but there was no difference with walking
distance, running, or jumping. The group undergoing fusion with sliding
corrective osteotomy was more satisfied with regard to cosmetic results and shoe
wear. The overall satisfactory rate in the group who underwent fusion with
sliding corrective osteotomy (92%) was superior to the group who underwent fusion
in situ (77%). Though our method of sliding corrective osteotomy does not provide
much improvement to the talus declination angle, it is suitable for those
patients with a "banana"-shaped calcaneus malunion. If the patient has prominent
anterior ankle pain caused by tibiotalar impingement, we believe that a
distraction subtalar arthrodesis would be more appropriate.
PMID- 10195295
TI - Basal closing wedge osteotomy for correction of hallux valgus and metatarsus
primus varus: 10- to 22-year follow-up.
AB - Between 1974 and 1985, 59 patients (83 feet) underwent basal closing wedge
osteotomy in combination with a bunionectomy and a lateral soft tissue release
for correction of hallux valgus and metatarsus primus varus at this institution.
Of the original 59 patients, 42 patients (60 feet) with at least 10 years of
follow-up (average, 194 months; range, 144-266 months) were available for this
study. Results were analyzed by review of the medical records and plain
radiographs, a standardized clinical questionnaire, and physical examination. Of
the 60 feet, patients rated outcomes as excellent or good in 51 feet (85%) and
rated cosmesis as excellent or good in 44 feet (73%). Radiographically at final
follow-up, hallux valgus and intermetatarsal angles averaged 19.9 degrees (range,
0-40 degrees) and 6.7 degrees (range, 0-18 degrees), respectively. The sesamoid
position was corrected from an average preoperative grade of 2.6 to a grade of
0.9 at final follow-up. The average shortening of the first metatarsal was 5 mm.
The disadvantages of the closing wedge osteotomy are that it is technically
demanding and it entails the risk of shortening, dorsal malalignment, and
metatarsalgia. In the current study, long-term complications included hallux
varus deformity (16 feet), dorsal malalignment (15 feet), and metatarsalgia (14
feet). Despite good correction of the intermetatarsal angle and sesamoid
position, the clinical results and the incidence of complications after basal
closing wedge osteotomy were not as favorable as those reported for other
procedures in the literature. Therefore, alternative procedures, such as the
basal crescentic osteotomy or the basal chevron osteotomy, should be used.
PMID- 10195296
TI - Radiographic evaluation of the calcaneocuboid joint: a cadaver study.
AB - Eighteen cadaver feet were used for radiographic evaluation of the calcaneocuboid
joint. The articular surface of the cuboid on all specimens was painted with a
radiopaque material. Fractures and 1-mm step-off of the fractures were simulated
in six specimens. The articular surface line and joint space could be visualized
maximally on an oblique radiograph without overlapping structures. The oblique
view is good for assessing the extent of the minor fracture-displacement, which
is normally obscured by overlapping projections in dorsoplantar and lateral
radiographs. If there is any doubt on the routine radiographs or any injury
involving the calcaneocuboid joint, an oblique view of the foot should be
performed. The early diagnosis and treatment of calcaneocuboid joint injuries may
minimize development of posttraumatic degenerative arthritis.
PMID- 10195297
TI - Risk of sural nerve injury with intramedullary screw fixation of fifth metatarsal
fractures: a cadaver study.
AB - The risk of injury to the sural nerve and its branches during operative
procedures performed on the lateral foot and ankle is well recognized; however,
there have been no anatomic studies demonstrating the proximity of the sural
nerve branches to the head of an intramedullary screw used for fixation of
fractures of the proximal fifth metatarsal. Dissection of 10 cadaver specimens,
after insertion of 4.5-mm screws, demonstrated that the screw head was within 2
mm of the dorsolateral branch of the sural nerve in five specimens and within 3
mm of eight specimens. Irritation of or injury to the nerve during screw
insertion may explain the persistence of pain after screw removal in some
patients. Furthermore, patients could sustain injury to the sural nerve at the
time of screw removal. Careful surgical technique, including the use of drill
guides and tissue protectors, may help lessen the risk of sural nerve injury and
subsequent neuroma formation.
PMID- 10195298
TI - Arthroscopic evaluation of the subtalar joint: does sinus tarsi syndrome exist?
AB - This is a retrospective review of 49 subtalar arthroscopies performed between
1989 and 1996. Patients were evaluated in the following areas: (1) preoperative
diagnosis, (2) preoperative tests and clinical evaluation, (3) intraoperative
findings, (4) postoperative diagnosis,(5) complications, and (6) clinical
outcome. Particular attention was paid to the accuracy of the preoperative
diagnosis, subtalar instability, intraoperative findings in sinus tarsi syndrome,
and clinical outcome. Overall, this study demonstrated a success rate of 94% good
and excellent results in the treatment of various types of subtalar pathologic
conditions with arthroscopic techniques. The Workers' Compensation cases reported
90% good and excellent results. The complication rate was low, with five minor
complications reported. The most common complication was a transient neuropraxia
involving branches of the superficial peroneal nerve. Of the 14 feet that had a
preoperative diagnosis of sinus tarsi syndrome, all the diagnoses were changed at
the time of arthroscopy. The postoperative diagnoses included 10 interosseous
ligament tears, two cases of arthrofibrosis, and two degenerative joints. Based
on these findings, "sinus tarsi syndrome" seems to be an inaccurate term that
should be replaced with a specific diagnosis. Arthroscopy is the tool that will
allow the orthopaedic surgeon to make a more accurate diagnosis.
PMID- 10195299
TI - Osteotomy for malunion of a talar neck fracture: a case report.
AB - A malunion of the talar neck after a Hawkins type II fracture/dislocation of the
talar neck occurred in a 34-year-old man after nonoperative treatment. Rigid
varus deformity of the forefoot was a source of severe pain and disability in
this patient. We describe our surgical technique for osteotomy of the talar neck
with insertion of a tricortical iliac crest bone graft to correct the deformity.
At follow-up (56 months), the patient had consistent relief of pain and was
employed at his preinjury job doing heavy labor. The score on the American
Orthopaedic Foot and Ankle Society Ankle-Hindfoot Scale improved from 11 points,
preoperatively, to 85 points, postoperatively. Radiographs showed maintenance in
the position of the osteotomy and no evidence of avascular necrosis in the talar
body. Evidence of arthrosis of the talonavicular joint was apparent
radiographically, but the patient did not complain of symptoms referable to this
area.
PMID- 10195300
TI - Inferomedial (subsustentacular) dislocation of the navicular: a case report.
AB - A unique case of subsustentacular dislocation of the navicular is presented. The
authors propose that such a severe displacement cannot occur until there is
complete instability across the whole midfoot. The mechanism of injury and the
treatment options are discussed. In the present case, there was late collapse of
the foot into abduction because the lateral column was not primarily stabilized.
Avascular necrosis is a common complication which leads to navicular collapse. A
midfoot arthrodesis gave a good result in our patient.
PMID- 10195301
TI - Tarsal tunnel syndrome: a review of the literature.
AB - Tarsal tunnel syndrome is an uncommon clinical entity. This article will review
the published reports on tarsal tunnel syndrome with respect to its anatomy,
cause, pathophysiology, clinical presentation, diagnosis, treatment, and results
of treatment in an attempt to improve understanding of this problem.
PMID- 10195302
TI - Revision tibiotalocalcaneal arthrodesis after a failed intramedullary rod: a
technique tip.
PMID- 10195303
TI - Vascularization and cartilage mineralization of the thyroid cartilage of Munich
minipigs and domestic pigs.
AB - Thyroid cartilages of Munich minipigs and domestic pigs were investigated by
polychrome sequential labeling, radiography, intravascular injections, histologic
examination and scanning electron microscopy in order to gain further insight
into the process of vascularization and cartilage mineralization. The
relationship between vascularization and cartilage mineralization has only been
studied in chondroepiphyses of long bones. Vessels branch off the perichondrial
vascular network and enter parts of the thyroid cartilage with a large transverse
diameter. Cartilage canals, which are perichondral invaginations, contain an
arteriole, a venule, a capillary network and connective tissue. The capillaries
form a glomerulus-like structure deep in the matrix of the cartilage.
Neighbouring cartilage canals do not display any anastomoses. Cartilage
mineralization occurs in large areas of the thyroid cartilage. It is only found
in the interterritorial extracellular matrix. Mineralization of the cartilage is
evident in areas supplied with cartilage canals as well as in non-supplied areas.
Mineralized interterritorial matrix is composed of circular structures of
different sizes fusing to form plaques. In scanning electron microscopy circular
structures appear as globules. It is possible to visualize the dynamic process of
cartilage mineralization with polychrome sequential labeling; it proceeds up to 4
microm per week. Distribution of cartilage canals reveals their nutritional role
for the cartilage. According to investigations in chondroepiphyses, cartilage
mineralization starts adjacent to the glomerular end of cartilage canals. In
contrast, no correlation between cartilage vascularization and the beginning of
cartilage mineralization of the thyroid cartilage of Munich minipigs and of
domestic pigs has been found.
PMID- 10195304
TI - Distribution of cytokeratin filaments and vimentin in developing human taste
buds.
AB - Taste buds in humans originate from approximately the 8th postovulatory week
under the influence of ingrowing nerve fibers. Since they develop from local
epithelium, it is of interest whether or not prospective taste cells maintain or
develop characteristics of epithelial cells that are different from those of the
adjacent epithelium during differentiation. The aim of this study was to monitor
changes of the distribution of the cytokeratin filaments (CKs) 8, 18, 19 and 20
("gastrointestinal" type), CK 7 ("ductal" type), and CK 13 (maturation "mucosa
type"), as well as vimentin in developing human taste buds and adjacent squamous
epithelium. With the exception of CK13, which remains negative in taste bud
anlagen and adult taste buds, all cytokeratins tested were present in taste
cells. With the progress of development, the distribution of CKs becomes more and
more restricted to taste cells and salivatory ducts as well as Ebner gland cells.
Only CK20 is exclusively specific to taste bud anlagen and sometimes to
individual bipolar cells occurring in early stages (week 8-9). Vimentin was
located mainly in mesodermal derivatives but also in perigemmal epithelial cells
during all stages of development. The occurrence of vimentin in "borderline"
epithelia that interface with underlying connective tissue, i.e., in a region of
discontinuity, may be associated with particular events in development, cell
migration or even dedifferentiation.
PMID- 10195305
TI - On the origin and prenatal development of the bovine adrenal gland.
AB - Decisive steps of bovine prenatal adrenal development were investigated in 46
embryos and fetuses using histological, electron microscopical, immuno-, enzyme
and lectin histochemical methods. About day 30, the intermediate mesoderm between
the cranial mesonephros and coelomic cavity is segmentally organized. It consists
of proliferating tissue complexes that are connected to the coelomic cavity by
vestigial nephrostomial tubules. This segmental organization soon disappears,
however, due to longitudinal fusion of the tissue complexes into a continuous
joined blastema. This blastema of intermediate mesodermal (nephric) origin
becomes positive for alkaline phosphatase at about 30 days, and slightly later
also for acetylcholinesterase. The most cranial portions of this common blastema
represent the adrenocortical anlage, the following portions the gonadal rete
blastema. A reevaluation of the comparative anatomical record revealed that a
nephric origin of adrenocortical or interrenal cells is a general feature of all
vertebrates and that the erroneous assumption of the lateral plate-derived
coelothelium as precursor of the adrenocortical (interrenal) blastema should be
definitively abandoned. The first adrenomedullary precursor cells become visible
in the bovine adrenal primordium at day 35. At 50 days, both components
(medullary and cortical precursors) are present as interpenetrating plates and
strands between large sinusoid vessels and exhibit a strong MIB-1 activity,
indicative of a high proliferation rate. About day 60 the cellular proliferation
slows down in some of the adrenocortical precursor cells, and the separation into
a visible cortex and medulla is initiated. From about day 80 on, the medullary
tissue coalesces into a large, continuous area in the interior of the gland,
surrounded by a narrow cortical glomerulo-fasciculata that becomes positive for
3beta-hydroxysteroid dehydrogenase at about day 90. Autonomous nerves penetrate
the blastemal region as early as day 31. When the separation into cortex and
medulla starts, the nerves are more concentrated in the latter. From 130 days on,
nerve fascicles reach the interior of the organ not only from its medial side,
but also from the capsule surrounding the gland. The penetrating bundles traverse
the zona glomerulo-fasciculata without ramification and split off at the border
to the medulla. Here, in the outer zone of the medulla, they constitute a
particularly dense plexus, whereas in the central medulla a less dense
innervation is observed. Up until 90 days, cells with the characteristic features
of primordial germ cells are present within the confines of the adrenal gland.
PMID- 10195306
TI - Parenchymal cells proliferate and differentiate in an organotypic slice culture
of the neonatal liver.
AB - We applied organotypic slice culture of neonatal mouse liver tissues to maintain
the parenchymal cells in ontogenesis and to investigate their proliferation and
differentiation. Cultured tissue spread gradually over 3 weeks. Small basophilic
cells formed several layers in the center of the cultured tissues, and a
monolayer of polygonal cells was seen at the periphery. Albumin- and alpha
fetoprotein-immunoreactions were seen in polygonal cells, as were proliferating
cell nuclear antigen-immunoreactions. Connexin 32- and 26-immunoreactions were
observed in small plaques on the membrane of the polygonal cells, and electron
microscopy showed gap junctional complexes. Ultrastructurally, polygonal cells
had a round nucleus and abundant cytoplasmic organelles, and bile canaliculi were
seen on the cytoplasmic membrane. Cytokeratin 19-immunoreactions were scattered
in clusters. There were ultrastructurally bile-duct-like structures with
microvilli on the inner surface of the cavity and tight junctions between their
constituent cells. Quantitative analysis of albumin-, alpha-fetoprotein- and
cytokeratin 19- or proliferating cell nuclear antigen-immunoreactivity in
parenchymal cells showed changes of their phenotypes or maintenance of their
proliferation in tissue culture. Our slice-culture system enabled us to maintain
and to develop parenchymal cells in the liver tissue for at least 3 weeks. The
findings suggest that organotypic slice culture applied to liver tissues in
ontogenesis may be a useful tool not only to maintain parenchymal cells but also
to investigate their proliferation and differentiation.
PMID- 10195307
TI - Postembryonic neural proliferation in the zebrafish forebrain and its
relationship to prosomeric domains.
AB - Large gaps of knowledge exist regarding postembryonic brain morphogenesis of the
zebrafish Danio rerio (Cyprinidae, Teleostei). The zebrafish represents together
with the frog (Xenopus), chick and mouse--one of four major models for the
genetic study of early brain development. Here, we used normal silver-stained
Bodian material and immunohistochemical material stained with a monoclonal
antibody against the proliferating cell nuclear antigen (PCNA, cyclin) to study
the morphogenetic appearance and location of proliferation zones of the zebrafish
brain between day 1 and day 10, focussing on the forebrain at day 5
postfertilization. Our results directly demonstrate that the dorsal telencephalic
proliferation zone (i.e. the pallium) extends--consistent with the process of
eversion--some distance laterally on top of the telencephalon. The subpallial
telencephalic proliferation consists of dorsal and ventral zones. The preoptic
region also includes dorsal and ventral proliferation zones. In the diencephalon
proper, separate proliferation zones are present in the habenula, and in the
periventricular cell masses of the dorsal thalamus, the ventral thalamus, and the
pretectum. More ventrocaudally, the latter three massive proliferation zones
appear to be replaced each by thinner, but distinct proliferation zones. Two of
them represent ventrocaudal continuations of the dorsal and ventral thalamus and
lie in the region referred to as the posterior tubercular area in adult
teleostean neuroanatomy. The third lies in the region of the nucleus of the
medial longitudinal fascicle. In addition, several hypothalamic proliferation
zones are present. The data for the diencephalon are largely in agreement with
the neuromeric model of brain organization of Puelles and Rubenstein (1993),
which is mostly based on amniote data. Generally, the understanding of the
prosomeric origin of teleostean prosencephalic cell masses may be regarded as
pivotal for their comparative interpretation.
PMID- 10195308
TI - Development of mechanoreceptor numbers in embryonic chick-quail chimeras.
AB - Our experiments addressed the problem of the regulation of the number of
mechanoreceptors by sensory axons and/or their peripheral target tissues.
According to a previous study (Zelena et al. 1997) white leghorn chickens have
more muscle spindles in the plantaris muscle (45.4+/-7.8; mean+/-SD) than the
Japanese quail (35.3+/-4.8) and significantly more Herbst corpuscles in the
crural region (380.0+/-85.0) than the quail (124.9+/-32.8). Embryonic chick-quail
chimeras were therefore used as a model with distinct recombinations of the nerve
supply and peripheral tissue for studying the developmental control of these
mechanoreceptors. The chick host leg bud was replaced with a quail leg bud of
equal age and vice versa on embryonic day 3, prior to the onset of innervation of
the periphery. Shortly before hatching the chimeras were sacrificed and muscle
spindles and Herbst corpuscles counted. Recombinations of chicken nerves with
quail limb buds have shown that the richer nerve supply by chick Ia axons induced
a significant increase in the number of muscle spindles in the plantaris muscles
(55.5+/-13.4) of the grafted quail limb. In some instances, a similar increase in
spindle numbers was also found in control legs grafted onto hosts of the same
species. In the reverse type of chimera where chick embryo legs were grafted onto
quail hosts, spindles developed in lower numbers (27.3+/-3.2). In that case the
lower number of Ia axons in quail nerves induced a lower number of spindles in
the chicken muscle. The numbers of Herbst corpuscles were, however, low in both
types of chimera. Quail legs grafted onto host chick embryos contained 126.8+/
26.4 corpuscles, presumably due to a restrictive influence of the smaller crural
area in the quail. Chick legs grafted onto quail hosts had only 99.6+/-34.1
crural corpuscles; the target area in chick embryo legs failed to attract more
quail axons and/or to induce axonal sprouting. The developmental regulation of
the number of the two types of mechanoreceptors examined in our study thus
differ. While sensory axons appear to play the dominant role in the development
of muscle spindles, their role seems to be restricted by hitherto unknown
peripheral factors during the development of Herbst corpuscles.
PMID- 10195309
TI - Connectivity in the somatosensory cortex of the adolescent rat: an in vitro
biocytin study.
AB - A promising way to elucidate neuronal information processing is to establish
detailed structure-function relationships of identified single neurons or
populations of nerve cells, especially their synaptic connectivity. This has been
greatly improved by the development of acute brain slice preparations. The
cellular physiology of the rodent primary somatosensory (barrel) cortex has been
extensively studied. However, for a meaningful interpretation of physiological
experiments the degree and pattern of connectivity has to be known for the
particular preparation. Since such studies are not available for rat (P15-25)
barrel cortex in vitro, we have traced the cortico-cortical and thalamo-cortical
connections in 400-microm-thick slices with biocytin. In coronal slices, a wealth
of axonal connections in retrograde and anterograde directions were heavily
labeled, resembling the full pattern of cortico-cortical projections described in
vivo. The most striking connections were vertical and horizontal connections
within the primary somatosensory cortex, as well as a columnar projection to the
secondary somatosensory cortex and beyond (mainly the parietal ventral area).
Electron microscopic extensions of the study indicated that the full possible set
of synaptic contacts with an adult-like appearance was already established in
these connections. In thalamo-cortical slices, strong reciprocal connections with
the ventrobasal (and to a much lesser extent also the posterior) thalamic nucleus
were always observed, together with an intensive ramification of fibers in the
reticular nucleus. A striatal terminal field was also consistently found. We
conclude that all major intracortical and thalamo-cortical connection are richly
preserved in the in vitro slice preparations of rats. Thus, these preparations
are suitable for elucidation of the functional interaction of the most crucial
brain structures involved in somatosensory information processing combining an in
vivo-like anatomical structure with the controlled environment of an in vitro
slice.
PMID- 10195310
TI - Smooth muscle cells and fibroblasts of the coronary arteries derive from
epithelial-mesenchymal transformation of the epicardium.
AB - Previous research has revealed that cells contributing to coronary vascular
formation are derived from the dorsal mesocardium, however, the fate of these
cells during consecutive stages of heart development is still unclear. We have
conducted a study regarding the recruitment of vascular components and the
subsequent differentiation into mature vessel wall structures with the aid of
immunohistochemical markers directed against endothelium, smooth muscle cells,
and fibroblasts. The proepicardial organ including an adhering piece of
primordial liver of quail embryos (ranging from HH15 to HH18) was transplanted
into the pericardial cavity of chicken embryos (ranging from HH15 to HH18). The
chicken-quail chimeras (n=16) were harvested from the early stage of endothelial
tube formation (HH25) to the late stage of mature vessel wall composition (HH43).
Before HH32 endothelial cells have invaded the myocardium to give rise to yet
undifferentiated coronary vessels. These endothelial cells are not accompanied by
other non-endothelial cells. The superficial epicardial layer changes from a
squamous mesothelium into a cuboid epithelium preceding media and adventitia
formation. Subsequently, a condensed area of mesenchymal cells delaminates from
the cuboidal lining extending toward the vessel plexus. Around the coronary
arteries, these mesenchymal cells differentiate into smooth muscle cells or
fibroblasts as shown by immunohistochemical markers. We conclude that epithelial
mesenchymal transformation of the epicardial lining delivers the smooth muscle
cells and fibroblasts of the coronary arterial vessel wall. Molecules involved in
epithelial transformation processes elsewhere in the embryo are also expressed
within the subepicardial layer, and are considered to participate in inducing
this process.
PMID- 10195311
TI - Psychoneuroimmunology: introductory comments on its physics and metaphysics.
PMID- 10195312
TI - Stress, depression and immunity: the role of defense and coping styles.
AB - It is by now widely recognized that acute and chronic stress have an impact on
the immune system. Acute stress may have a stimulating effect on the immune
system, while in the case of chronic stress--and in particular in depression--the
immune system may be down-regulated. However, there is considerable individual
variability in the immune response to stress. This seems to a large extent to be
determined by the subject's way of dealing with stress. The perception and
evaluation of a stressor and the specific ways of stress coping may in different
ways be related to various aspects of the stress response: sympathetic nervous
system (SNS) activation and activation of the hypothalamic-pituitary-adrenal
(HPA) axis, both systems affecting the immune system. Prolonged exposure to
stressors or to severe life stresses may outweigh the person's coping resources
leading to feelings of depression. The affective changes with the accompanying
changes in the HPA axis are one of the hypothesized mechanisms underlying the
immune changes in depression. It should be noted that the relationship between
depression and immunity is affected by several other factors, such as gender and
age and other personal resources. Increasing the subject's abilities to cope with
stress and to reduce the negative affect by psychological interventions may on
the other hand have a beneficial effect on the immune system.
PMID- 10195313
TI - Repressive/defensive coping, endogenous opioids and health: how a life so perfect
can make you sick.
AB - Hyperactivity of endogenous opioid systems has been postulated to mediate the
associations between defensive/repressive coping styles, enhanced stress
responsivity, and reduced immunocompetence. Study 1 examined whether
repressive/defensive coping would be associated with greater sensitivity to
opioid antagonism. Judgments of the painfulness of ascending series of
electrocutaneous stimulation applied to the forearm were determined before and
after the administration of naloxone and placebo in 38 men and 42 women. All
subjects were healthy with a mean age of 32.9 years. Naloxone (10 mg i.v.) and
placebo were administered in double-blind fashion and counterbalanced. Subjects
were classified as High- and Low-defensive and repressive copers on the basis of
scores on the Marlowe-Crowne Social Desirability Scale and the Balanced Inventory
of Desirable Responding, respectively. High Self-Deception was associated with
naloxone-induced hyperalgesia, whereas no effects of naloxone on pain ratings
were observed in low-Self-Deceptive subjects. In Study 2, resting plasma beta
endorphin levels were found to be positively correlated with defensiveness in men
(n = 26), but not women (n = 44). Study 3 examined 82 healthy subjects (mean age
= 28.7 years). Beta-endorphin/defensiveness correlations were found to be greater
following, compared to prior to, electrical nociceptive stimulation in men (n =
49), but unrelated in women (n = 33). These findings are consistent with the
hypothesized endorphinergic dysregulation associated with repressive/defensive
coping styles and are discussed in terms of the immuno-regulatory implications of
such a dysregulation.
PMID- 10195314
TI - Nitric oxide and biopterin in depression and stress.
AB - Depression has been hypothesized to be related to the reduced biosynthesis of
neurotransmitters such as serotonin, noradrenalin and dopamine. Much past
research has also been devoted to dysregulation of the hypothalamic-pituitary
adrenal (HPA) axis in depression. The present article reviews the evidence
linking tetrahydrobiopterin, a co-factor in the biosynthesis of
neurotransmitters, and nitric oxide, an apparent neuroendocrine modulator of the
HPA axis, to the immune system and to neuronal control within affective disorder
and stress. On the basis of this review, it is suggested that future
psychoneuroimmunological research should more fully explore the possible role of
tetrahydrobiopterin and nitric oxide in depressive disorders.
PMID- 10195315
TI - The time dimension in stress responses: relevance for survival and health.
AB - Within the Cognitive Activation Theory of Stress (CATS), the stress response
occurs whenever there is a discrepancy between what the organism is expecting,
and what really exists. It affects the biochemistry of the brain, mobilizes
resources, affects performance, and endocrine, vegetative, and immune systems.
Initial positive feedback and feed-forward mechanisms are gradually changed by
homeostatic mechanisms. Slower reactive hormones such as cortisol seem to dampen
the initial response. The time course may depend on psychological mechanisms.
Subjects with efficient coping show the fast- and short-lasting catecholamine
response, while subjects with high defense mechanisms (related to stimulus
expectancies) may show more signs of prolonged activation. Non-coping individuals
show a sustained general activation which may develop into somatic disease or
illness.
PMID- 10195316
TI - On the role of immunological factors as mediators between psychosocial factors
and cancer progression.
AB - Thirty-eight prospective studies on the role of psychological factors in cancer
initiation and progression are reviewed. Despite the availability of many
prospective studies, there is no certainty about the role of any specific factor.
An important reason might be that the interactions among several psychological
factors, and the interactions of psychological and biomedical risk factors, have
rarely been studied. Some evidence has been found that a low level of social
support, a tendency towards helplessness, and repression of negative emotions are
factors that promote cancer progression. The effect of psychological factors has
been more convincingly demonstrated with respect to cancer progression than
cancer initiation, and more convincingly in intervention than in natural history
studies. Possible mechanisms mediating associations between psychological factors
and disease outcome are discussed. The role of immunosurveillance seems modest
overall, and alternative pathways are suggested.
PMID- 10195317
TI - Depression and immunity: clinical factors and therapeutic course.
AB - While many reports describe associations between depressive disorders and altered
immunity, findings have not been fully consistent. Diagnostic subtype,
demographic factors such as age and gender, medical characteristics, and the
immune measures selected for assessment may have contributed to the heterogeneous
findings. In a study of 21 medically healthy young adults with major depression,
we found, consistent with previous reports, evidence of increased lymphocyte
activation to mitogen challenge and decreased natural killer (NK) cell numbers
and function during acute depression. Fifteen subjects were followed
longitudinally. T, CD4+, CD29+, and CD45RA+ lymphocytes and T-cell mitogen
responses decreased significantly (P<0.05) during 6 weeks of pharmacotherapy and
concurrent clinical improvement. There was no change in NK activity or CD56+
cells. The longitudinal effects appeared unrelated to tricyclic antidepressant
levels. Changes in the immune system with short-term clinical improvement in
depressed patients are not uniform providing further evidence that several
mechanisms are involved in the altered immunity associated with clinical
depression.
PMID- 10195318
TI - Alterations in immune functions during normal aging and Alzheimer's disease.
AB - It is thought that aging induces immune changes, which are related to the
pathophysiology of Alzheimer's disease (DAT). In this study, the total number of
leukocytes, white blood cell differentiation, mitogen-induced lymphocytic
proliferation, neutrophil phagocytosis and superoxide release, and prostaglandin
E2 (PGE2) production by mitogen-stimulated whole blood cultures were
comparatively investigated between healthy adults (range 22-45 years) and healthy
elderly volunteers (range 70-91 years), and between DAT patients (range 56-94
years) and age-matched control subjects. Healthy elderly volunteers showed
significantly lower phytohemagglutinin (PHA)-induced lymphocyte proliferation and
percentage and absolute number of basophils than young volunteers. In normal
volunteers, there were significant and negative correlations between age and the
number of basophils. Patients with DAT showed a trend toward significantly higher
PHA-induced lymphocyte proliferation and significantly decreased percentage and
absolute number of large unstained cells than healthy volunteers. In DAT
patients, the total number of leukocytes and the percentage and number of
neutrophils were positively correlated with age. All other immune-inflammatory
variables were not significantly altered either by the aging process or DAT. The
present study suggests that aging and DAT may differently affect some immune
variables.
PMID- 10195319
TI - The immunological and psychological effects of bereavement: does grief counseling
really make a difference? A pilot study.
AB - This study evaluates psychological and immunological functioning after
bereavement and the influence of group counseling. Eighteen widows (bereaved
within 3 months of enrolment) and a reference group of 10 married control
subjects were asked to fill in self-report scales and to donate a blood sample
(T1). After T1, half of the widows (the experimental group) were randomly
assigned to grief counseling (13 sessions over 4 months), while the other
subjects (the control group) received no treatment. Seven months after
bereavement (T2) or, in the case of the experimental group, immediately after the
intervention, a follow-up was conducted in the widowed subsample using the same
measures. Blood samples were analyzed to determine the total number of white
blood cells, number of lymphocyte subsets, natural killer cell activity (NKCA)
and lymphocyte proliferative response to phytohemagglutinin (PHA), anti-CD3 and
pokeweed mitogen (PWM). At T1, we found significant differences between widows
and non-widows regarding both psychological and immunological measures. Widows
felt more anxious, depressed, hostile and agoraphobic. At T1, widows had a lower
number of the CD19+CD5+ B cell subpopulation. The cell function tests for T and B
cells showed higher responses in widows (lymphocyte proliferation response to
PHA, anti-CD3 and PWM). No significant difference in NKCA was found between
widows and non-widows. At T2, there appeared to be no significant difference
between widows and non-widows on the psychological measures. With respect to the
immunological measures, widows and non-widows showed no significant differences
for the total number of white blood cells, number of lymphocyte subsets and NKCA.
Consistent with our findings at T1, the lymphocyte proliferation response to PHA,
anti-CD3 and PWM at T2 appeared to be higher in widows than in non-widows.
Comparing the experimental group (widows) and the control group (widows) with
respect to psychological measures at T1, widows in the experimental group felt
more insufficient and had more sleep disturbances. With respect to the
immunological measures, no differences were found between those two groups. When
the same two groups were again compared at T2, no differences were found in any
of the psychological or immunological measures (lymphocyte sub-populations,
proliferation tests and the NKCA).
PMID- 10195320
TI - Psychosocial predictors of psychological, neurochemical and immunological
symptoms of acute stress among breast cancer patients.
AB - The purpose of this study was to determine the impact of locus of control, social
support and their interaction on acute stress indicators as a consequence of the
communication of the results of a breast biopsy. Immunological and psychological
indicators were evaluated in 50 patients with breast tenderness. We found little
evidence for the existence of a relationship between psychosocial variables
considered to be stress indicators and acute stress symptoms. Concerning the
results of the first assessment, only the relation between locus of control and
psychological distress was meaningful. With regard to the existence of a
relationship between psychosocial variables and natural killer cell system
indicators, only the number of natural killer cells (NKC) could be explained by
the psychosocial model including locus of control, perceived social support from
relatives and the interaction between locus of control and perceived social
support from relatives.
PMID- 10195321
TI - Immune dysfunction associated with chronic professional stress in nurses.
AB - The relationship between chronic professional stress in nurses and immunity as
well as the possible impact of psychopathology upon this relationship have been
examined. Sixty subjects were selected on the basis of high/low scores on
professional stress and psychopathology. Chronic professional stress appeared to
be associated with immune dysfunction including signs of immune activation
(increased numbers of cells expressing the interleukin-2 receptor, especially
CD4+CD25+ cells) and possibly immune suppression (decrease in percentage of
natural killer cells). The increase in activation markers, CD3+CD16CD56+ cells
and serum neopterin was most pronounced in the group with high stress/low
psychopathology whereas the decrease in CD8+CD11b+ cells was most pronounced in
the group with high stress/high psychopathology. It is hypothesized that in the
presence of chronic stress distinct psychological mechanisms are associated with
specific immune dysfunctions.
PMID- 10195322
TI - The effect of depressive symptomatology on plasma cortisol responses to acute
bicycle exercise among post-menopausal women.
AB - The present study was designed to elucidate the effect of depressive
symptomatology on the cortisol response to strenuous exercise. Thirteen healthy,
post-menopausal women participated in this study. The results show that acute
bicycle exercise activates the hypothalamic-pituitary-adrenal (HPA) axis
resulting in rapid increases in plasma cortisol. Concerning the effect of
depressive symptomatology on cortisol release during physical performance, we
found a trend toward a negative relation between the level of depression and the
change in cortisol measured after termination of the exercise, but it failed to
reach statistical significance, probably due to the small sample size.
Interestingly, we found a significant negative correlation between basal cortisol
levels and cortisol release to the exercise protocol. Although this finding is
preliminary, it seems to suggest that a sustained activation of the HPA axis may
coincide with an adrenal insufficiency in response to physical performance of
post-menopausal women.
PMID- 10195323
TI - Diffusional anisotropy is induced by subcellular barriers in skeletal muscle.
AB - The time- and orientational-dependence of phosphocreatine (PCr) diffusion was
measured using pulsed-field gradient nuclear magnetic resonance (PFG-NMR) as a
means of non-invasively probing the intracellular diffusive barriers of skeletal
muscle. Red and white skeletal muscle from fish was used because fish muscle
cells are very large, which facilitates the examination of diffusional barriers
in the intracellular environment, and because they have regions of very
homogeneous fiber type. Fish were cold-acclimated (5 degrees C) to amplify the
contrast between red and white fibers. Apparent diffusion coefficients, D, were
measured axially, D(axially) and radially, D(radially), in small muscle strips
over a time course ranging from 12 to 700 ms. Radial diffusion was strongly time
dependent in both fiber types, and D decreased with time until a steady-state
value was reached at a diffusion time approximately 100 ms. Diffusion was also
highly anisotropic, with D(axially) being higher than D(radially) for all time
points. The time scale over which changes in D(radially) occurred indicated that
the observed anisotropy was not a result of interactions with the thick and thin
filament lattice of actin and myosin or restriction within the cylindrical
sarcolemma, as has been previously suggested. Rather, the sarcoplasmic reticulum
(SR) and mitochondria appear to be the principal intracellular structures that
inhibit mobility in an orientation-dependent manner. This work is the first
example of diffusional anisotropy induced by readily identifiable intracellular
structures.
PMID- 10195324
TI - Quantifying 1H decoupled in vivo 31P brain spectra.
AB - Our objective was to develop a precise method for quantification of in vivo
proton decoupled 31P spectra from the human brain. This objective required that
an appropriate spectral model be created and that the quantification was
performed using a non-subjective fitting technique. The precision of the
quantification was assessed using Cramer-Rao standard deviations and compared
using two different spectral models: one containing a pair of peaks representing
2,3-diphosphoglycerate, the other excluding this metabolite. The data was
quantified using a Marquardt-Levenberg (ML) algorithm incorporating prior
knowledge with a Hankel singular value decomposition (HSVD) performed initially
to provide parameter estimates for the ML algorithm. Quantification was performed
on two different in vivo 2-D CSI 31P data sets: the first examined 11 normal
controls, the second examined a single individual six times. Spectra from a
region in the parieto-occipital cortex were analyzed. The Cramer-Rao standard
deviations were significantly lower for some metabolites with 2,3
diphosphoglycerate in the model: in the repeat study mobile phospholipids (p =
0.045) and phosphocholine (p = 0.034), and in the 11 controls mobile
phospholipids (p = 0.003) and Pi (p = 0.002).
PMID- 10195325
TI - Rapid and continuous monitoring of cerebral perfusion by magnetic resonance line
scan assessment with arterial spin tagging.
AB - A new approach is presented for rapid and continuous monitoring of cerebral
perfusion which is based upon line-scan MR column imaging with arterial spin
tagging (AST) of endogenous water. Spin tagging of arterial water protons is
accomplished using adiabatic fast passage inversion, followed by acquisition of
the perfusion sensitive MR signal from a column placed at the desired level
through the brain using line scan localization techniques. A perfusion sensitive
line scan is followed by a non-perfusion sensitive line scan, and perfusion is
calculated pixel-by-pixel from the intensity difference of the two lines.
Continuous perfusion measurements are reported with temporal resolution of 10 s
in pixels of volume 0.027 cm3 or less. Examples of the methodology are given
during hypercapnic challenge induced with carbon dioxide, and during an ischemic
event induced by reversible middle cerebral artery occlusion. The method is also
used to characterize the signal response as a function of arterial inversion time
and post inversion acquisition delay. These methods permit rapid and continuous
monitoring of cerebral perfusion with high spatial resolution, and can be
interleaved with MR measurements of diffusion and T1 to follow the progression of
cerebral events during physiological or pharmacological intervention.
PMID- 10195326
TI - Spatial distribution of deoxymyoglobin in human muscle: an index of local tissue
oxygenation.
AB - The proximal histidyl NdeltaH signal of myoglobin is detectable in 1H NMR spectra
of myocardial and skeletal muscle, and its intensity reflects the intracellular
oxygenation. At 1.5 Tesla (T), the typical field strength of clinical magnetic
resonance imaging (MRI) magnets, the paramagnetic relaxation contribution
decreases sufficiently to permit the implementation of chemical shift imaging
technique to map the spatial distribution of the deoxy Mb NdeltaH signal from
human gastrocnemius muscle. One and two-dimensional chemical shift imaging
experiments reveal clearly the localized deoxy Mb signal in muscle and
consequently the spatial distribution of the cellular oxygenation. The results
indicate the feasibility to assess the pO2 in tissue regions and to directly
study the regulation of oxidative metabolism in human tissue.
PMID- 10195327
TI - Metabolite changes in neonatal rat brain during and after cerebral hypoxia
ischemia: a magnetic resonance spectroscopic imaging study.
AB - Cerebral metabolite concentrations were measured in infant rats using proton
magnetic resonance spectroscopic imaging. Measurements were made prior to, during
and after exposure of rats (6- and 7-day-old) to unilateral cerebral hypoxia
ischemia (right carotid artery occlusion +2h 8% oxygen). Data clustered according
to age and outcome-6-day-old animals with no infarct and 7-day-old animals with
infarct. In 6-day-old animals, cerebral lactate concentration increased during
hypoxia-ischemia, particularly ipsilateral to the occlusion, and returned to
normal soon after the end of hypoxia. There were no major changes in N-acetyl
aspartate levels (NAA) in this group and no regions of hyperintensity on T2 or DW
weighted images at 24 h. In the 7-day-old animals, lactate increased during
hypoxia-ischemia and remained elevated in the first hour after reperfusion.
Furthermore, lactate remained at 258+/-117% and 233+/-56% of pre-hypoxic levels,
24 and 48 h post-hypoxia, respectively. NAA concentrations ipsilateral to the
occlusion decreased to 55+/-14% during hypoxia, recovered early post-hypoxia and
again decreased to 61+/-25% and 41+/-28% at 24 and 48 h post-hypoxia-ischemia,
respectively. The infarct volumes measured by diffusion weighted and T2 weighted
MRI at 48 h post-hypoxia were 152+/-40 mm3 and 172+/-35 mm3, respectively. Thus,
irreversible damage correlated well with measured in vivo lactate and NAA
changes. Those animals in which NAA was unaltered and lactate recovered soon
after hypoxia did not show long-term damage (6-day-old animals), whereas those
animals in which NAA decreased and lactate remained elevated went on to
infarction (7-day-old animals).
PMID- 10195328
TI - In vivo magnetic resonance spectroscopy and dynamic contrast enhanced imaging of
the prostate gland.
AB - The quantitation of in vivo 1H MR spectroscopy and dynamic contrast enhanced MR
imaging is described for patients with histologically confirmed prostate
adenocarcinoma and benign prostatic hypertrophy (BPH). Results are presented
which suggest that combined use of these techniques may be helpful in improving
the characterization of prostate pathologies and ultimately increase the staging
accuracy of magnetic resonance.
PMID- 10195329
TI - Regional and directional anisotropy of apparent diffusion coefficient in rat
brain.
AB - Quantitative diffusion maps were recorded in normal rat brain. In multi-slice
sections covering the whole brain, strong variation of the apparent diffusion
coefficient (ADC) was observed depending on slice position at constant gradient
direction. Furthermore, a varying difference between apparent diffusion
coefficients depending on gradient direction was found, reaching 32% in the
cortex of the ventral-most horizontal sections while showing equal ADC on the
dorsal cortex side. The regional variation and directional anisotropy of the ADC
was not restricted to white matter but was described for both cortical and
subcortical brain tissue. From diffusion coefficients along the three major field
gradient directions (ADCx, ADCy, ADCz), the average ADC (ADCaverage) was
determined from the trace of the diffusion tensor (D) as 653+/-28 microm2/s for
parietal cortex and 671+/-32 microm2/s for lateral cortex, independent of
position along the sagittal direction. From these observations about the regional
diffusion anisotropy, a more stringent protocol for the description of ischemic
ADC changes is proposed.
PMID- 10195330
TI - Multi-component apparent diffusion coefficients in human brain.
AB - The signal decay with increasing b-factor at fixed echo time from brain tissue in
vivo has been measured using a line scan Stejskal-Tanner spin echo diffusion
approach in eight healthy adult volunteers. The use of a 175 ms echo time and
maximum gradient strengths of 10 mT/m allowed 64 b-factors to be sampled, ranging
from 5 to 6000 s/ mm2, a maximum some three times larger than that typically used
for diffusion imaging. The signal decay with b-factor over this extended range
showed a decidedly non-exponential behavior well-suited to biexponential
modeling. Statistical analyses of the fitted biexponential parameters from over
125 brain voxels (15 x 15 x 1 mm3 volume) per volunteer yielded a mean volume
fraction of 0.74 which decayed with a typical apparent diffusion coefficient
around 1.4 microm2/ms. The remaining fraction had an apparent diffusion
coefficient of approximately 0.25 microm2/ms. Simple models which might explain
the non-exponential behavior, such as intra- and extracellular water
compartmentation with slow exchange, appear inadequate for a complete
description. For typical diffusion imaging with b-factors below 2000 s/mm2, the
standard model of monoexponential signal decay with b-factor, apparent diffusion
coefficient values around 0.7 microm2/ms, and a sensitivity to diffusion gradient
direction may appear appropriate. Over a more extended but readily accessible b
factor range, however, the complexity of brain signal decay with b-factor
increases, offering a greater parametrization of the water diffusion process for
tissue characterization.
PMID- 10195331
TI - Paraquat induced activation of transcription factor AP-1 and apoptosis in PC12
cells.
AB - Drugs and certain environmental toxins may be responsible for the pathogenesis of
Parkinson's disease. We have used paraquat as a model toxin for this study since
paraquat has been shown to make its way to the nerve terminals and cause cell
death of dopamine neurons by oxidative injury. We have shown by the
electrophoretic mobility shift assay that paraquat, together with low
concentrations of chelated iron (Fe++/DETAPAC), induced the activation of
transcription factor AP-1 binding activity to DNA. Under similar conditions we
also found by both a DNA laddering assay procedure and by terminal
deoxynucleotidyl transferase assay (TUNEL assay) that paraquat also induces
apoptotic cell death. Interestingly, both apoptotic cell death and AP-1/DNA
binding activity induced by paraquat were blocked by cyclohexamide and genistein,
indicating that both the AP-1/DNA binding activation and apoptosis induced by
paraquat are closely related. Moreover, cells were also protected from paraquat
toxicity in the presence of antioxidant defense enzymes SOD and catalase. The
results support the hypothesis that oxidative stress may be contributing to the
apoptotic cell death of dopaminergic neurons, leading to the manifestation of
Parkinson's disease. Since paraquat was an important herbicide in the mid 20th
Century, our results have the important implication that exposure to
environmental toxins such as paraquat may induce Parkinson's disease.
PMID- 10195332
TI - Effect of acute and chronic administration of dehydroepiandrosterone on (+/-)-1
(2,5-dimethoxy-4-iodophenyl)-2-aminopropane-induced wet dog shaking behavior in
rats.
AB - It has been reported that dehydroepiandrosterone (DHEA) or dehydroepiandrosterone
sulfate (DHEA-S) is associated with affective disorders and that pathology of
affective disorders are related with dysfunction of serotonin(5-HT)-2A receptor
mediated responses. In this study, we investigated the effect of DHEA on (+/-)-1
(2,5-dimethoxy-4-iodophenyl)-2 aminopropane (DOI), 5-HT-2A receptor agonist,
induced wet dog shaking behavior (WDS) in rats. Acute treatment with DHEA
inhibited the DOI-induced WDSs dose dependently. This inhibition was recovered by
opioid receptor antagonist, naltrexone. 5-HT-2A receptor-mediated WDSs were
desensitized after chronic treatment with DOI, however chronic treatment with
DHEA had no effect on this desensitization. Chronic treatment with DHEA had no
facilitating effect of chronic dexamethasone treatment on DOI-induced WDSs. These
findings may lead the possibility that DHEA has the inhibitory effect of 5-HT-2A
mediated signaling pathway via non-genomic action.
PMID- 10195333
TI - Modulation of striatal acetylcholine concentrations by NMDA and the competitive
NMDA receptor-antagonist AP-5: an in vivo microdialysis study.
AB - The effects of local perfusion with the competitive NMDA receptor antagonist 2
amino-5-phosphonovalerate (AP-5) and the glutamate receptor agonist N-methyl-D
aspartate (NMDA) on release of extracellular acetylcholine (ACh) and choline (Ch)
in the dorsolateral striatum were studied using in vivo microdialysis in freely
moving rats. AP-5 caused a dose-dependent decrease in ACh release that was
counteracted by the addition of NMDA. Perfusion with AP-5 also decreased Ch
levels. Local perfusion with NMDA induced an elevation of ACh release in low (10(
5) M), but not high (10(-2) M and 10(-3) M) concentrations, that were associated
with massive cellular death. These inhibitory effects of AP-5 and the stimulatory
effect of NMDA in non-neurotoxic dosages on ACh release provide further evidence
for a tonic stimulation of striatal cholinergic interneurons by glutamatergic
neurons via NMDA receptors.
PMID- 10195334
TI - Clinical parkinsonism in dementia patients with substantia nigra Lewy bodies.
AB - In a retrospective clinicopathological study, we examined the substantia nigra
(SN) of 48 dementia patients with SN Lewy bodies (LBs) to determine if the
severity of degeneration correlated with either the occurrence of signs of
parkinsonism at dementia presentation or with the frequency of treatment for
parkinsonism during the disease course. The SN specimens were graded for
microscopic degeneration using a semi-quantitative five-tiered scale. Whereas no
correlation was found between the grade of degeneration and occurrence of signs
at presentation (r = -0.16, p = 0.18), with 16 of 38 patients having had signs
reported, a more severe grade was statistically correlated with an increased
frequency of treatment during the course (r = 0.41, p = 0.004), with ten of 41
patients having been treated for parkinsonism. Contrary to our expectations, we
found that fewer than half of the patients with the two most severe grades of
degeneration presented with signs of parkinsonism or were ever treated for
parkinsonism.
PMID- 10195335
TI - The effects of (+)-UH232 and (-)-DS121 on local cerebral glucose utilization in
rats.
AB - Although (+)-UH232 (cis-(+)-5-methoxy-1-methyl-2-(n-dipropylamino)tetralin) and (
)-DS121 (S(-)-3-(3-(cyanophenyl)-N-n-propylpiperidine) are both preferential
dopamine autoreceptor antagonists, (-)-DS121 is a more effective behavioral
stimulant and dopamine releasing agent. To further compare these two agents,
Sokoloff's 2-deoxyglucose autoradiography method was used to study the effects of
(+)-UH232 and (-)-DS121 on regional brain energy metabolism. (+)-UH232, 30 mg/kg
i.p., depressed metabolism in 37 of 65 brain regions and antagonized the
stimulant effects of amphetamine. (-)-DS121, 30 mg/kg i.p., exhibited a strong,
nonsignificant trend towards an increase in regional brain energy metabolism by
itself and enhanced the stimulant effects of amphetamine. The data demonstrate
dramatic differences in the effects of two autoreceptor antagonists on regional
brain energy metabolism. It is concluded that, compared to (+)-UH232, (-)-DS121
is a more effective stimulant of brain energy metabolism and autoreceptor
antagonist owing to its greater ability to increase DA release.
PMID- 10195337
TI - Internally and externally guided voluntary saccades in unmedicated and medicated
schizophrenic patients. Part I. Saccadic velocity.
AB - Saccadic eye movements were elicited in 30 schizophrenic patients before and in
17 of these 30 during antipsychotic treatment with neuroleptics, and compared
with those of 12 age-matched controls under three different conditions: (a) the
gap paradigm, which tests the visually triggered and visually guided saccades;
(b) the anti-task paradigm, which tests the internally guided, visually triggered
saccades; and (c) the memory paradigm, which tests the internally triggered and
guided saccades. Eye movements were recorded by DC electro-oculography, and the
peak eye velocities for the different saccades were calculated. We found that
antipsychotic treatment with neuroleptics reduces the peak saccadic eye velocity.
This effect is larger for internally guided saccades than for externally
triggered and guided eye movements. The saccadic velocity of the unmedicated
schizophrenic patients did not differ from that of the controls. Since patients
with diseases of the basal ganglia primarily show abnormalities of the internally
guided and triggered saccades, our findings indicate that neuroleptics influence
the oculomotor loop through the basal ganglia and that this loop, by means of
neuroleptic influence on the brainstem saccadic burst generator, also influences
the peak velocity of the internally guided saccades. This contradicts the current
idea of the role of the cortical input to the brainstem saccadic burst generator,
which is thought to not be involved in the determination of saccadic velocity.
PMID- 10195336
TI - Effects of antipsychotic drugs on dopamine and serotonin contents and
metabolites, dopamine and serotonin transporters, and serotonin1A receptors.
AB - The effects of neuroleptics have been attributed to dopamine (DA) receptor
blockade; however, other neurotransmitters, in particular serotonin (5-HT), have
also been implicated. In this study, we examined the effects of clozapine and
haloperidol on the distribution of DA and 5-HT transporters, on endogenous DA, 5
HT and their major metabolites, and on 5-HT1A receptors. Adult male Sprague
Dawley rats were treated with either haloperidol (1 mg/kg/day, i.p.), clozapine
(20 mg/kg/day, i.p.) or saline for 21 days, and following 3 days of withdrawal,
the brains were removed. Tissue levels of DA and 5-HT and their metabolites were
measured by high-performance liquid chromatography in 16 brain regions, while
quantitative autoradiography with [125I]RTI-121, [3H]citalopram and [3H]8-OH-DPAT
was employed to label DA transporters, 5-HT transporters and 5-HT1A receptors,
respectively. After haloperidol, densities of 5-HT transporters were increased in
the dorsal insular cortex and in the ventral half of caudal neostriatum, while 5
HT1A receptors augmented in cingulate cortex but decreased in the entorhinal
area. After clozapine, [3H]citalopram labelling was increased in ventral
hippocampus, ventral caudal neostriatum and nucleus raphe dorsalis, but decreased
in medio-dorsal and latero-dorsal neostriatum as well as in substantia nigra.
Binding of [3H]8-OH-DPAT following clozapine was decreased in frontal, parietal,
temporal and entorhinal cortices but increased in the CA3 division of Ammon's
horn. The changes in 5-HT transporters in nucleus raphe dorsalis and substantia
nigra, as well as the 5-HT1A receptor down-regulations caused by clozapine but
not by haloperidol, may explain effects obtained with clozapine and other
atypical neuroleptics. There were no modifications in densities of DA
transporters, nor of tissue DA levels, after the chronic neuroleptic treatments.
The results are in line with previous suggestions that a certain degree of
tolerance to neuroleptics develops, in spite of profound D1 and D2 receptor
changes that persist during the entire chronic treatment with these psychotropic
agents.
PMID- 10195338
TI - Internally and externally guided voluntary saccades in unmedicated and medicated
schizophrenic patients. Part II. Saccadic latency, gain, and fixation suppression
errors.
AB - Saccades were elicited in 30 schizophrenic patients before medication, in 17 of
them during medication with neuroleptics, and in 12 healthy controls using six
paradigms that tested different types of saccades: (a) the externally triggered
and visually guided saccades; (b) the externally triggered and internally guided
saccades (anti-saccades); and (c) the internally triggered and internally guided
saccades (memory-guided saccades). Latency of the primary saccade, gain (eye
amplitude to target amplitude), and percentage of unwanted saccades (fixation
suppression errors) were calculated. The externally triggered and externally
guided saccades were only slightly affected in the patients, indicating that the
function of parieto-tectal pathways was preserved. In contrast, the internally
guided and externally triggered saccades showed abnormally long latencies,
slightly smaller gains, and an increased rate of suppression errors regardless of
the medication status. These findings were even more pronounced in the internally
triggered and internally guided saccades such as memory-guided saccades.
According to animal experiments and studies on patients with disorders of the
basal ganglia, the performance of these saccades is based on the function of the
pre- and dorsolateral frontal cortex and its connections to the basal ganglia.
The minimal improvement of some of the parameters after clinical improvement and
during treatment with neuroleptics suggests that the eye-movement deficits are
associated with abnormalities of schizophrenia, which do not basically change
under medication with neuroleptics. The observed effects of neuroleptics also
argue against a primary abnormality in the dopaminergic input to the frontal
cortex - basal ganglia oculomotor loop and support the view that there is a
primary disturbance of the cortical input to the oculomotor loop through the
basal ganglia in schizophrenics.
PMID- 10195339
TI - Generators of brain electrical activity in patients with Wilson's disease.
AB - Electroencephalographic (EEG) generators were investigated in 13 patients
suffering from hepatolenticular degeneration with and without neurological
symptoms and in 13 healthy subjects for comparison by the use of FFT
approximation. Quantitative assessment of motor deficits and psychiatric
disturbances was correlated with EEG features. We found mainly an increase in
delta activity, a decrease in alpha activity combined with a more posterior
localisation of the EEG generators in the delta band and a more anterior one in
the alpha band in patients compared with healthy controls. The localisation of
the EEG generators in the patients with clinical apparent neurological symptoms
were in all frequency bands more superficial compared with controls and patients
without neurological symptoms. With longer duration of the disease, the lower the
premorbid intelligence the more posterior was the delta EEG generator localised.
Although the alpha EEG generator was more anteriorly localised with longer
duration of the disease and more severe cognitive deficits, it was more
superficial with more pronounced psychiatric symptoms, more severe cognitive
deficits, lower premorbid intelligence and more pronounced motor disabilities.
With more pronounced psychiatric symptoms and cognitive deficits, the beta EEG
generator was more anteriorly localised. The present study demonstrated that a
significant deviant EEG pattern exists between patients with and without clinical
neurological symptoms and that stage-dependent alterations in psychiatric
symptoms and cognitive ability are reflected on the EEG.
PMID- 10195340
TI - Application of a new statistical approach to evaluate a clinical trial with panic
disorder patients.
AB - In clinical trials in psychiatry, changes in severity are usually measured with
ordinal level scales which are applied repeatedly during the trial, showing a
constant decline in psychopathology scores as treatment leads to improvement.
Previous non-parametric tests for repeated measures in factorial designs did not
test the hypothesis that scale scores decrease constantly during the trial. A
recently developed "rank test for ordered alternatives in a mixed model" was
developed and applied to the data of a clinical trial in panic disorder. Thirty
seven outpatients with panic disorder and agoraphobia (PDA) were treated with
imipramine (75-150 mg/day) in an 8-week open, prospective trial. Patients with
intercurrent agoraphobia were instructed in practising self-exposure in their
agoraphobic situations. The total score on the Panic and Agoraphobia Scale, the
Hamilton Anxiety Scale (HAMA) and the Clinical Global Impression Scale (CGI) were
used as the main efficacy measures. The new rank test showed significant
treatment results in all scales applied. Treatment results were excellent, as was
shown by a decrease in the average Panic and Agoraphobia Scale severity scores
from 28.9 (range 14-45) to 13.3 (range 0-37; rank statistic Tn = 6.7; p <
0.0001). The largest effect size r(w) of all clinician-rated scales was seen with
the observer-rated version of the Panic and Agoraphobia Scale, although closely
followed by the CGI and the HAMA. Among the self-rated scales, the Panic and
Agoraphobia Scale also showed the largest effect size. All five subscores of the
Panic and Agoraphobia Scale showed significant improvements. The highest
treatment effect sizes were seen in the "panic attacks" subscore, followed by the
"anticipatory anxiety" subscore. The new statistical test applied in this study,
which has some advantages in comparison with previously applied tests, is
suitable for psychiatric treatment evaluations since it can also be applied in
the case of discrete repeated measurements.
PMID- 10195341
TI - Observation levels in acute psychiatric admissions.
AB - It was our objective to compare the influence of patients' variables and
circumstances of admission on the use of observation levels in acute psychiatric
admissions in a British mental health unit. We performed a prospective case note
survey of all acute psychiatric admissions during 28 consecutive days in June and
July 1991 within a large teaching hospital and a traditional psychiatric hospital
in Nottingham, England. We compared, the demographic characteristics of 88
consecutive admissions, admission procedures, clinical data, initial observation
levels and changes in observation levels. As for the results, most patients were
admitted outside of regular working hours (weekends or after 5 p.m.). Most
patients were placed on intermediate (close) observation. The most important
factor associated with the choice of observation level was the legal status of
the patient (chi2 = 14.79, df = 2, p < 0.001, Fisher's exact test p < 0.0001).
There were significantly fewer incidents (chi2 = 7.72, df= 2, p < 0.05, Fisher's
exact test p < 0.01) on the highest (special) category of observation. The
observation policy of the unit was not followed consistently. The number of
factors contributing to the choice of observation levels reflects the complexity
of the task facing the staff. Special observation is an effective method of
managing acutely disturbed patients. The time of admission of most patients
implies that more trained staff should be provided outside of regular hours.
Clinical staff should be regularly trained in the use of observation procedures.
It should be a regular topic in clinical audit.
PMID- 10195342
TI - Alcoholism in homeless men in the mid-nineties: results from the Bavarian Public
Health Study on homelessness.
AB - Parallel to structural economic changes homelessness has become publicly more
visible and has received increased media attention in Western industrialized
countries. Most studies on mental illness and homelessness in recent years were
carried out in North America but only few studies in Europe have dealt with these
issues. The goals of the present study were (1) to assess alcohol abuse and
dependence as well as other mental disorders in a representative sample of
homeless men in Munich using reliable methods of case identification (Structured
Clinical Interview for DSM-IV (SCID)), (2) to compare homeless alcoholics with
homeless non-alcoholics in our sample on relevant variables, and (3) to compare
our data from the Munich sample with data obtained by others. According to our
results, the life-time prevalence of any SCID-DSM-IV Axis I diagnoses was 93.2%
and the lifetime prevalence of substance use disorder was 79.6%. The single most
prevalent diagnosis among homeless males in Munich was alcohol dependence (life
time 72.7%); alcohol abuse (life-time 5.5%) and drug abuse/dependence were
considerably lower in prevalence (life-time 19.1%) (weighted data). A higher rate
of psychotic disorders was found for non-alcoholic homeless men. Data show that
alcoholism and its consequences were more severe in the Munich as compared to
North American samples. Homeless alcohol dependent men showed a high comorbidity
with other mental disorders (life-time) such as mood disorders (36.4%), anxiety
disorders (16.4%), drug abuse/dependence (18.9%) and psychotic disorders (4.5%).
Of those with alcohol dependence at some time during their life 59.1% had
experienced at least one other life-time mental disorder. Alcohol-related
behavioral patterns and symptoms as well as general social functioning are
described. Considering the very high prevalence of alcohol dependence (frequently
in combination with other mental disorders), the participation in alcohol
rehabilitation and other services as well as self-help groups was rather low
among Munich homeless alcoholics. Currently homeless men in Germany are
adequately supplied with food, clothes, and shelter but psychiatrically (and
medically) neglected. Existing concepts and programs for dealing with these
problems need to be implemented.
PMID- 10195343
TI - Cannabis and schizophrenia: results of a follow-up study.
AB - A total of 39 schizophrenic patients with a history of current cannabis abuse at
index admission was compared with a control group of schizophrenics without
substance abuse matched for age, gender, and year of admission. At follow-up
after 68.7+/-28.3 months, 27/ 39 cases and 26/39 controls could be investigated.
8/27 cases (30%) had continued cannabis abuse, 6/27 (22%) had become alcohol
abusers. Only one patient of the control group had started abusing alcohol.
Patients with previous cannabis abuse had significantly more rehospitalizations,
tended to worse psychosocial functioning, and scored significantly higher on the
psychopathological syndromes "thought disturbance" (BPRS) and "hostility" (AMDP).
These results confirm the major impact of cannabis abuse on the long-term outcome
of schizophrenic patients.
PMID- 10195344
TI - Absence of a subgroup of chronic schizophrenia in monozygotic twins. Consequences
for considerations on the pathogenesis of schizophrenic psychoses.
AB - In the region of Lower Franconia, Germany, all twins born after 1930 and
hospitalized for a schizophrenia spectrum psychosis were ascertained in a
systematic twin study comprising 22 monozygotic (MZ) and 25 dizygotic (DZ) pairs.
One aim of the study was to compare concordance rates between MZ and DZ pairs
with regard to various diagnostic classifications. Two experienced psychiatrists
independently classified the probands according to DSM-III-R, ICD-10, and
Leonhard's classification. Schizophrenic psychoses were found among MZ and DZ
pairs in equal proportions according to DSM-III-R and ICD-10 criteria. In
contrast, when Leonhard's classification was applied it became apparent that
systematic schizophrenias, which represent the core group of schizophrenias in
Leonhard's nosology, were completely lacking among the 34 ill MZ twins. Among the
30 ill DZ twins, 6 suffered from a systematic schizophrenia (p < 0.01).
Unsystematic schizophrenias and cycloid psychoses occurred among MZ twins at a
frequency of 58.8% and 41.2%, respectively. In the course of his own twin
investigations, Leonhard also observed an absence of systematic schizophrenias in
MZ twins, although his twins were not systematically ascertained. This striking
finding requires an explanation regarding its significance for the etiology of
chronic schizophrenic psychoses. In view of the absence of other conclusive
theories, one speculative explanatory model is that specific psychosocial
factors, i.e., a lack of communication during childhood, may result in distinct
biological damage to functional brain systems and, thus, may play a role in the
pathogenesis of these psychoses.
PMID- 10195345
TI - Progressive maturation resistance to microcystin-LR cytotoxicity in two different
hepatospheroidal models.
AB - To develop three-dimensional (3D) cytotoxicity models further, microcystin
induced cytoskeletal disruption was tested in two different models of
multicellular hepatocyte aggregate formation (hepatospheroids). Rat hepatocyte
suspensions were seeded either onto poly(2-hydroxyethylmethacrylate)-treated
culture wells (poly-HEMA) or in a rotating wall vessel (RWV) device which
provides minimal shear forces and enhances differentiated 3D growth. Ninety
percent of spheroids forming on poly-HEMA tended to fuse and form nonhomogeneous
multilobular structures by day 4 of incubation. In contrast, spheroids cultured
in the low-shear environment formed homogeneous aggregates that averaged 126 + 10
microm diameter in size at day 7. Microcystin-LR (10(-6) mol/L) was put into
contact (90 min in serum-free medium) with hepatocyte suspensions and spheroids
formed in both systems for 1, 4 or 7 days. As already described, microcystin-LR
(after 90 min), induced cytoskeletal disruptions (blebs) in 98% of the isolated
primary hepatocytes maintained in suspension. In 3D cultures, blebs were detected
only on poly-HEMA nonhomogeneous early prespheroids. All other mature spheroids
(poly-HEMA or RWV) exposed to the toxin did not exhibit obvious morphological
signs of toxicity. Moreover, microcystin-LR pre-incubation with hepatocyte
suspension prevented the formation of conventional spheroids. In conclusion, the
low-shear, simulated-microgravity environment generated high yields of regularly
engineered spheroids. In both models, progressive resistance of mature spheroids
to microcystin-LR-induced cell deformation developed with time in culture.
Microcystin-LR inhibition of the formation of rat hepatospheroids in isolated
hepatocyte suspension could be used as a complementary biological assay for
detection of the presence of biologically active microcystin-LR in water samples.
PMID- 10195346
TI - Genotoxic potential of cyclosporin A in patients with renal transplantation.
AB - We analyzed the induction of sister chromatid exchange (SCE) by cyclosporin A
(CsA) as a marker of genotoxic potential. In 30 patients undergoing renal
transplantation, SCE induction was tested before the introduction of CsA and 3
months later. We found that SCE frequency increased significantly at the end of 3
months. To our knowledge, this is the first study demonstrating in vivo induction
of SCE by CsA in humans. We conclude that CsA has a genotoxic potential on human
lymphocytes.
PMID- 10195347
TI - Involvement of phospholipase A2 activation in anthrax lethal toxin-induced
cytotoxicity.
AB - The molecular mechanism of cytotoxic effect exerted by the lethal toxin (LeTx) of
Bacillus anthracis is not well understood. In the present study, using primary
culture of mouse peritoneal macrophages, we have investigated possible cytotoxic
mechanisms. LeTx was not found to induce high levels of nitric oxide (NO)
production for NO-mediated toxicity. Fragmentation of DNA, a biochemical marker
of apoptosis, was not observed in LeTx-treated cells. Pretreatment of cells with
antioxidants such as melatonin and dehydroepiandrosterone (DHEA) did not protect
the LeTx-induced cytotoxicity. However, addition of phospholipase A2 (PLA2)
inhibitors (quinacrine, p-bromophenacyl bromide, manoalide, butacaine) to the
culture medium resulted in the inhibition of cytotoxicity of LeTx in a dose
dependent manner. LeTx-induced cytotoxicity was also inhibited by the tyrosine
specific protein kinase inhibitor genistein, but not by the protein kinase C
inhibitors staurosporine or H-7. The results of these studies indicate a role for
PLA2 and protein kinase in the cytotoxic mechanism of macrophages by anthrax
lethal toxin.
PMID- 10195348
TI - p53 expression and TGF-alpha-induced replication of hepatocytes isolated from
rats exposed to the carcinogen diethylnitrosamine.
AB - Previous reports indicate that the expression of transforming growth factor alpha
(TGF-alpha) is increased in enzyme-altered foci (EAF) arising in livers of rats
treated with a carcinogen. Here we have investigated the effects of TGF-alpha on
EAF cells in vitro. Hepatocytes were isolated from rats that had received
repeated treatment with diethylnitrosamine (DEN) and whose livers contained
glutathione S-transferase P (GST-P)-positive EAF. Primary cultures of GST-P
positive and GST-P-negative hepatocytes were exposed to TGF-alpha. TGF-alpha (20
40 ng/ml) increased DNA replication in the GST-P-negative, but not in the GST-P
positive cells. Furthermore, it was shown that this effect on GSTP-negative cells
could be blocked by p53 antisense oligonucleotides. We conclude that EAF
hepatocytes do not respond to TGF-alpha in vitro. This lack of response may
reflect the attenuated expression of p53 in these cells. These data corroborate
previous findings that, in response to DNA damage, many EAF hepatocytes do not
accumulate p53.
PMID- 10195349
TI - Immune functions of the human skin. Models of in vitro studies using Langerhans
cells.
AB - Human skin constitutes the first immune defense barrier. Among the epidermal
cells, the Langerhans cells, which belong to the dendritic cells, represent the
pivotal cells in cutaneous immune reactions. The possibility of obtaining human
Langerhans cells either from human skin or by in vitro generation from CD34+
hematopoietic precursors opens the way to studies reproducing the successive
steps of the Langerhans cells' role in contact dermatitis.
PMID- 10195350
TI - Development of structure-activity relationships (SARs) in allergic contact
dermatitis.
AB - One of the major objectives at the end of this century is the development of
"alternative" tests for the evaluation of the pharmacological and/or
toxicological activity of newly developed molecules. Contact allergy is no
exception to the rule and many research programs have been started to develop in
vitro techniques for the detection of allergizing compounds. In parallel with
these biological studies, another approach is becoming important and will no
doubt become more so, namely, the study of structure activity relationships
(SARs). This consists of using molecular or physicochemical properties to predict
and, in certain cases, quantify the allergizing potential of a new molecule
without using any biological test. Three main approaches are currently under
study: the creation of allergy databases, the design of "expert" computerized
systems, and the development of quantitative SARs. These three often
complementary approaches are still at the development stage, but we can begin to
see their potential and limitations. The aim of this article is not to give an
exhaustive description of all the systems developed worldwide, but to illustrate
each approach by giving some important examples.
PMID- 10195351
TI - Mechanisms of drug-induced allergic contact dermatitis.
AB - Allergic contact dermatitis is induced by a wide variety of drugs that trigger
specific immune responses following topical exposure. Identified chemical
structures involved in such reactions include the mercuric and thiosalicylic acid
groups of thimerosal, the diphenylketone group of the anti-inflammatory drug
ketoprofen, the amide or ester structure of local anesthetics, and the side-chain
and thiazolidine ring of beta-lactams. The T cell responses to such compounds
involve CD4+ and CD8+ alphabeta+ T lymphocytes and also CD4 /CD8 gammadelta+ T
cells. Although "T helper 2" cytokine production by drug-specific human T cells
from patients with allergic contact dermatitis has been described, T helper 1
like and T cytotoxic 1-like responses clearly play key roles in this cutaneous
reaction.
PMID- 10195352
TI - Use of skin cell cultures for in vitro assessment of corrosion and cutaneous
irritancy.
AB - Skin cell culture is one of the most promising tools for in vitro evaluation of
both cutaneous irritancy and corrosion. New culture methodologies, including
three-dimensional reconstruction of skin, allow the evaluation of a wide range of
compounds and complex formulations. A number of tests have already been developed
for the evaluation of cytotoxicity and many end-points are now currently used,
including cell viability, alteration of cell growth or cell function. In recent
years parameters more closely related to in vivo irritancy effects such as
synthesis of inflammatory mediators and/or their release by keratinocytes after
exposure to potential skin irritants have been evaluated. This paper reviews
technological aspects and results of validation using skin cell culture for in
vitro assessment of corrosion and skin irritancy. Advantages and limits of skin
cell cultures are also presented. Current questions about the validation process
of cutaneous irritation and corrosion are also considered.
PMID- 10195353
TI - The role of shock organs in influencing the clinical expression of allergy.
PMID- 10195354
TI - The clinical expression of allergy in the lungs.
PMID- 10195355
TI - Regulation and modulation of eosinophil effector functions.
PMID- 10195356
TI - Controversial aspects of adverse reactions to food. European Academy of
Allergology and Clinical Immunology (EAACI) Reactions to Food Subcommittee.
PMID- 10195357
TI - Cutaneous responses to substance P and calcitonin gene-related peptide in chronic
urticaria: the effect of cetirizine and dimethindene.
AB - BACKGROUND: Neuropeptides appear to participate in the pathogenesis of chronic
urticaria. The purpose of this study was to investigate the cutaneous responses
to substance P (SP) and calcitonin gene-related peptide (CGRP) in delayed
pressure urticaria patients (DPUpt) and chronic idiopathic urticaria patients
(CIUpt) compared to healthy adults (HA), and also to evaluate the effect of H1
antagonists on these responses. METHODS: Wheal (W) and flare (F) reactions to
intradermally (ID) injected SP, CGRP, histamine (H), and diluent controls were
evaluated in nine CIUpt, nine DPUpt, and nine HA at 3, 7, 15, 30, 60, and 120 min
after injection. Maximal W and F, area under curve (AUC), and time of W and F
disappearance were calculated at baseline and 4 h after a single dose of 20 mg
cetirizine (Ce), 4 mg dimethindene (Di), or placebo (P), in a double-blind,
placebo-controlled (DBPC), crossover, randomized study. RESULTS: CIUpt exhibited
enhanced and longer lasting W reactions to SP and CGRP (AUC: P<0.05) than HA; SP-
and CGRP-induced F (at maximal concentration) were larger and longer lasting in
CIUpt than in HA (P<0.003 and P = 0.004, respectively). In the DPU group, SP
induced W and F responses were intermediate in magnitude compared to CIUpt and
HA. In HA, SP-induced flares were significantly suppressed only by Ce (P<0.020),
while both Ce and Di affected SP-induced W and F in the two patient groups
(P<0.05). CGRP-induced flare inhibition by the two H1-antagonists was also
greater in the urticaria patient groups than in HA. CONCLUSIONS: CIUpt and, to a
lesser extent, DPUpt showed enhanced SP- and CGRP-induced W and F reactions. CGRP
elicited an immediate W and F response, followed by prolonged erythema. H1
antagonists partially affected W and F reactions to SP and only the F response
induced by CGRP; this effect was more pronounced in the urticaria patient groups
than in HA. Overall, W and F cutaneous responses to SP were suppressed to a
greater extent by Ce than Di.
PMID- 10195358
TI - Soluble E-selectin correlates with disease activity in cyclosporin A-treated
patients with atopic dermatitis.
AB - BACKGROUND: The expression of adhesion molecules on endothelial cells regulates
leukocyte migration. The level of soluble adhesion molecules which are shed into
the circulation is known to reflect the degree of inflammation, and this level
can therefore be used as an indicator of disease activity. The objective of this
study was first to investigate the relationship between sE-selectin levels and
disease activity parameters (scores of extent, severity, itch, and sleep) in
atopic dermatitis (AD) patients, and second to determine the effect of therapy
with an immunosuppressive drug (cyclosporin A) on sE-selectin levels. METHODS:
Fourteen patients with severe AD and 41 healthy controls were studied. sE
selectin was measured by ELISA both 2 weeks before therapy with cyclosporin A and
after 16 weeks of treatment. RESULTS: At baseline, the level of sE-selectin was
significantly higher in patients with AD than in healthy control subjects
(P<0.0001). After treatment of AD with cyclosporin A, there was a significant
reduction of the sE-selectin levels (P<0.0001). In addition, changes in sE
selectin levels significantly correlated with changes in disease activity
parameters such as severity (P<0.002) and extent of disease (P<0.049).
CONCLUSIONS: Soluble E-selectin is a new serologic marker in AD which reflects
disease activity. Therefore, soluble E-selectin may be a useful parameter in the
monitoring of this disease.
PMID- 10195359
TI - Onset of action of mometasone furoate nasal spray (NASONEX) in seasonal allergic
rhinitis.
AB - BACKGROUND: Mometasone furoate nasal spray (MFNS, NASONEX ), is a new synthetic
corticosteroid with considerable efficacy in the treatment of seasonal and
perennial rhinitis and less than 0.1% systemic absorption. This study was
designed to evaluate the time of onset of action of MFNS. The subjects were
evaluated over the course of 2 weeks during the spring allergy season. METHODS:
The effects of MFNS 200 microg given once daily for 2 weeks were evaluated in a
randomized, multicenter, double-blind, placebo-controlled study in 201 patients
with seasonal allergic rhinitis. Clinically significant onset of action was
assessed prospectively by special patient diary cards kept during the first 3
days of treatment. RESULTS: By 12 h after initial dosage (the earliest
evaluation), 28% of patients in the MFNS group experienced clinically significant
relief, compared with 13% of those given placebo (P = 0.01). Median time to at
least moderate symptom relief in patients who received MFNS was 35.9 h, compared
with more than 72 h in patients given placebo (P<0.01). By 72 h, 64% of the
patients receiving MFNS experienced at least moderate relief, compared with 40%
of those treated with placebo (P<0.01). Both patient and physician ratings of
symptom severity, response to treatment, and overall condition of rhinitis
indicated significant (P<0.01) superiority of MFNS over placebo. MFNS was well
tolerated, with adverse events comparable to placebo. CONCLUSIONS: MFNS provided
rapid onset of clinically significant symptom relief in patients with seasonal
allergic rhinitis.
PMID- 10195360
TI - Latex allergy in Saudi children with spina bifida.
AB - BACKGROUND: Children with spina bifida (SB) are exposed to latex soon after birth
during bladder catheterization, rectal disimpaction, and multiple surgical
procedures. IgE-mediated latex-allergic reactions have been reported recently in
these children. Our study was designed to assess the prevalence of allergic
reactions to latex products in a group of Saudi Arabian children with SB in a
tertiary care hospital. METHODS: Fifty-nine patients, aged 1-20 years, with SB
were evaluated by a questionnaire on type of latex reactions; family and personal
history of other allergic disorders, such as asthma, rhinitis, and urticaria;
type and number of surgical procedures; and frequency of bladder catheterization
and manipulation with latex materials. Confirmation of latex sensitivity was
measured by skin prick test (SPT), CAP test, and latex skin challenge. RESULTS:
Allergy to latex was detected in 25% of the study group. There was a significant
variation in allergic reaction by sex (males 42%, females 12%) (P<0.01), use of
catheters (yes 38%, no 13%) (P<0.05), and urologic surgery (yes 60%, no 18%)
(P<0.01). The number of surgical procedures, age of patient, and V-P shunt were
not significantly related to allergic reactions. CONCLUSIONS: Our findings
support previous studies indicating a high prevalence of latex allergy among SB
patients. The CAP test was a more sensitive measure of latex allergy in SB
patients than SPT or latex challenge. There was significant correlation with
urologic procedures and the use of urethral catheters.
PMID- 10195361
TI - Fatty acids in substitute formulas for cow's milk allergy.
AB - BACKGROUND: The role of dietary fats in food-related allergic symptoms is
increasingly being investigated, since the pivotal role of fat-derived
inflammatory substances, e.g., leukotrienes, has been realized. The objective of
this study was to describe the fatty acid composition of several commercially
available infant formulas that are used as substitutes for adapted cow's milk
formulas. METHODS: Samples of nine formulas (two soy, two extensively hydrolyzed
casein, three extensively hydrolyzed whey, and two amino-acid-based formulas) and
human milk as control were analyzed by gas chromatography. RESULTS: The quantity
of fatty acids in the formulas was within the breast-milk range. The percentage
of energy derived from fat was below the European Society for Pediatric
Gastroenterology and Nutrition recommendations in two cases, but, in the others,
it roughly met the recommendations. The percentage of energy derived from
linoleic acid was as recommended in all but two cases, where it was higher than
recommended. As indicated by a quality indicator, the linoleic to alpha-linolenic
acid ratio, altogether four formulas were within either the recommendations or
the analyzed breast-milk range. In three cases, it was 1.5-2.5 and in two cases 4
5 times higher than recommended. CONCLUSIONS: There are recommendations for
infant formulas to meet nutritional requirements of fat intake, and the analyzed
formulas are in most cases within the suggested ranges. However, little is known
of requirements in allergic or inflammatory conditions, and whether these
described fatty acid compositions are pro- or anti-inflammatory.
PMID- 10195362
TI - Latex and amoxicillin-provoked occupational asthma.
PMID- 10195363
TI - Open challenge to nuts in children.
PMID- 10195364
TI - Prevalence of latex-specific IgE in blood donors: an Italian survey.
PMID- 10195365
TI - Angioedema due to losartan.
PMID- 10195366
TI - Allergic contact dermatitis to propylene glycol.
PMID- 10195367
TI - Phenytoin hypersensitivity syndrome with fatal evolution.
PMID- 10195368
TI - Pattern of food-induced anaphylaxis in children of an Asian community.
PMID- 10195369
TI - Occupational asthma caused by esparto grass (Stipa tenacissima) fibers.
PMID- 10195370
TI - A new apple extract.
PMID- 10195371
TI - Combined immediate- and delayed-type hypersensitivity to metamizole.
PMID- 10195372
TI - Seizures induced by NSAID.
PMID- 10195373
TI - Immediate urticaria to Euphorbiaceae.
PMID- 10195374
TI - Tyr-Ala-Hexarelin, a synthetic octapeptide, possesses the same endocrine
activities of Hexarelin and GHRP-2 in humans.
AB - Hexarelin (HEX) and GHRP-2 are two synthetic hexapeptides, superanalogs of GHRP
6, belonging to GH secretagogue (GHS) family. GHS act via specific receptors at
both the pituitary and the hypothalamic level to stimulate GH release both in
animals and in humans. However, GHS also possess significant PRL- and
ACTH/cortisol-releasing activity. Tyr-Ala-HEX as well as Tyr-Ala-GHRP-6 are, in
turn, synthetic octapeptides generally used to perform binding studies because of
their easy iodination. However, their endocrine activities have never been
studied in humans. To clarify the endocrine activities of Tyr-Ala-HEX, in 7 young
adult volunteers we compared the effects of the maximal effective dose of HEX
(2.0 microg/kg i.v.) or GHRP-2 (2.0 microg/kg i.v.) with the same one of Tyr-Ala
HEX on GH, PRL, ACTH and cortisol levels. Basal GH, PRL, ACTH and cortisol levels
in all testing sessions were similar. The administration of placebo did not
modify hormonal levels. HEX and GHRP-2 administration induced the well known
strong GH response (Cmax, mean+/-SE: 77.3+/-6.0 and 74.1+/-12.1 microg/l; AUC,
mean+/-SE: 2596.7+/-251.1 and 2480.0+/-343.6 microg*min/l). These responses were
similar to that induced by Tyr-Ala-HEX (63.7+/-18.5 microg/l; 1986.6+/-622.4
microg*min/l). Moreover, HEX, GHRP-2 and Tyr-Ala-HEX had the same significant
stimulatory effect on PRL (14.9+/-2.5, 12.3+/-2.0 and 10.0+/-1.5 microg/l;
497.8+/-61.8, 480.4+/-66.9 and 415.8+/-58.5 microg*min/l), ACTH (48.0+/-10.1,
51.4+/-10.6 and 44.9+/-12.2 pg/ml; 1531.6+/-235.7, 1586.7+/-277.0 and 1338.1+/
164.5 pg*min/ml) and cortisol (179.9+/-10.0, 181.2+/-14.1 and 149.7+/-20.1
microg/l; 8465.0+/-406.6, 8689.2+/-788.1 and 6295.2+/-797.0 microg*min/l). Also
the mean Tmax of the endocrine responses to HEX, GHRP-2 and Tyr-Ala-HEX were
similar. In conclusion, the present results demonstrate that in humans Tyr-Ala
HEX is a GH secretagogue as potent as HEX and GHRP-2, two GHRP-6 superanalogs.
Tyr-Ala-HEX also shares with HEX and GHRP-2 the same PRL- ACTH- and cortisol
releasing activity.
PMID- 10195375
TI - Serum IGF-I and IGFBP-3 levels for the assessment of disease activity of
acromegaly.
AB - To assess the disease activity of acromegaly in patients, we measured the changes
in serum growth hormone (GH) levels during oral glucose tolerance test and the
basal serum levels of insulin-like growth factor I (IGF-I) and insulin-like
growth factor-binding protein 3 (IGFBP-3) in 29 acromegalic patients and 30
health persons served as normal controls. Based on the clinical and laboratory
criteria, acromegaly was in an active state of disease in 18 patients and was
inactive in the other 11 patients. Basal serum IGF-I levels were 177+/-116 ng/ml
(mean+/-SD), 250+/-135 ng/ml and 810+/-297 ng/ml in the normal subjects, the
inactive and active acromegalic patients, respectively. Basal serum IGFBP-3
levels were 1.71+/-1.29 microg/ml, 2.98+/-0.96 microg/ml and 6.82+/-1.31
microg/ml in the normal controls, the inactive and active acromegalic patients,
respectively. Serum levels of IGF-I and IGFBP-3 significantly correlated with
each other in the normal subjects as well as the patients. Both IGF-I and IGFBP-3
levels were significantly higher in the group of patients with active acromegaly
than inactive acromegalic patients and the normal subjects but there was not
statistically difference between the normal controls and the inactive
acromegalics. While serum IGF-I levels presented considerable overlapping
instances among the three groups, the serum IGFBP-3 of inactive patients and the
normal controls could rarely reach 4.44 ng/ml, the lowest value of the active
acromegalics. The serum IGF-I and IGFBP-3 levels declined with increased age in
normal controls, but not in the patients with acromegaly. There was no sex
predilection of serum IGF-I and IGFBP-3 found in our study. The results of this
study indicated that the serum IGFBP-3 level is an important laboratory parameter
for assessing growth hormone function in humans, and might be a more reliable
discrimination for the disease activity of acromegaly than the serum IGF-I is.
PMID- 10195376
TI - TRH is a tonic secretagogue in growth hormone secreting but not in nonfunctioning
pituitary tumors.
AB - In most patients with growth hormone (GH) secreting pituitary adenomas and
clinically nonfunctioning pituitary tumors (NFPT) the intravenous injection of
thyrotropin releasing hormone (TRH) augments the secretion of GH and subunits of
gonadotropin hormones respectively. Similar hormone responses to TRH have been
detected in rat pituitary cell lines and in primary human pituitary tumor
cultures in vitro. Nevertheless the TRH effect on tumor hormonal secretion has
not been well characterized. In the present study we examined TRH-induced hormone
secretion in GH secreting tumors and in NFPT in vitro. Cultured cells secreted
betaLH and betaFSH (NFPT) or GH (GH secreting adenomas) up to 14 days in culture.
In NFPT TRH (10(-8) mol/l) elicited peak betaLH and betaFSH secretion at 60 to 90
min, with no further increase at 24 h. TRH-stimulated GH secretion peaked at 90
120 min, and decreased after 3 h, but a secondary rise occurred after 24 h of
incubation. Chronic daily exposure to TRH followed by an acute TRH challenge
resulted in a further increase of GH secretion after one hour. In contrast, acute
TRH administration following chronic exposure did not elicit increased P-subunits
secretion in NFPT. Coadministration of cycloheximide did not change TRH induced
beta-subunits secretion in NFPT. However, when it was administered 24 h prior to
TRH, it blocked both basal and TRH induced beta-subunits levels in NFPT.
Cycloheximide had no effect on basal or stimulated GH secretion when administered
concomitantly or 24 h before TRH. Incubation of cultured GH secreting tumors with
cycloheximide during 5 days blocked both basal and TRH stimulated GH secretion,
thus indicating dependency on protein synthesis during the chronic, secondary
phase. Since the acute secretion was not affected by coadministration of
cycloheximide, these early increases in hormone levels apparently reflect the
release of stored hormone. In summary, GH secreting adenomas and NFPT differ
significantly in their hormonal response to continuous exposure to TRH. The
mechanisms underlying the sustained effect of TRH on GH secretion in vitro remain
to be investigated. If endogenous TRH exerts a similar continuous effect it may
contribute to the disregulated GH secretion in acromegaly.
PMID- 10195377
TI - Carbohydrate-induced thermogenesis in obese women. Effect of insulin and
catecholamines.
AB - Results of studies on diet-induced thermogenesis in obese persons are
contradictory. A number of factors have been postulated to mediate the obligatory
and facultative component of thermogenesis. This study was designed to
investigate some further factors mediating the carbohydrate-induced thermogenesis
in obese women. In 13 obese women, thermogenic responses to glucose and fructose
were compared and related to subsequent hormonal changes. The thermogenic effect
after fructose ingestion was significantly (p<0.006) higher in comparison with
glucose, despite lower values for both glucose and insulin concentrations.
Carbohydrate oxidation was significantly higher after fructose (81+/-7 E% vs 62+/
10 E% p<0.01) while oxidation of fat was lower (10+/-9 E% vs 21+/-12 E% p<0.01).
These effects may partly be due to the de novo lipogenesis and/or to changes in
cellular metabolism. No clear relationship could be found between thermogenesis
and the activity of the sympathetic nervous system, as expressed by urinary
catecholamine levels. These results indicate that not insulin but the cellular
rate of carbohydrate metabolism is responsible for the thermogenic response to
different carbo-nutrients.
PMID- 10195378
TI - Calcium modulation of the renin-aldosterone axis.
AB - Changes in the extracellular calcium concentration have important effects on
hormone secretion. In vitro, kidney juxtaglomerular cells have been shown to
secrete renin in an inverse relationship to the extracellular calcium
concentration. The effect of physiologic changes in calcium on renin secretion in
humans is less clear. We therefore investigated the effects of physiologic
changes in extracellular calcium levels on renin and aldosterone secretion in 7
healthy men. Serum ionized calcium, ACTH, plasma renin activity (PRA), and
aldosterone levels were serially measured during 90-min infusions of dextrose,
disodium edetate (EDTA) and calcium gluconate, and the latter two infusions were
repeated with dexamethasone pre-treatment. ACTH levels decreased during the 5%
dextrose in water and the EDTA infusions but increased during the calcium
infusion. Similarly, PRA and aldosterone levels fell during the D5W and EDTA
infusions but this decrease was absent with increments in calcium levels.
Dexamethasone administration suppressed ACTH and the aldosterone response to
calcium but did not affect the PRA response to the calcium infusion. Our data
indicate that increases in calcium within the physiological range blunt the
diurnal decline in both PRA and aldosterone. This appears to be a direct effect
of calcium on PRA but mediated through ACTH in the case of aldosterone.
PMID- 10195379
TI - Transient pseudo-hypoaldosteronism following resection of the ileum: normal level
of lymphocytic aldosterone receptors outside the acute phase.
AB - Pseudo-hypoaldosteronism (PHA) is due to mineralocorticoid resistance and
manifests as hyponatremia and hyperkalemia with increased plasma aldosterone
levels. It may be familial or secondary to abnormal renal sodium handling. We
report the case of a 54-year-old woman with multifocal cancer of the colon, who
developed PHA after subtotal colectomy, ileal resection and jejunostomy. She was
treated with 6 g of salt daily to prevent dehydration, which she stopped herself
because of reduced fecal losses. One month later she was admitted with signs of
acute adrenal failure, i.e. fatigue, severe nausea, blood pressure of 80/60 mmHg,
extracellular dehydration, hyponatremia (118 mmol/l); hyperkalemia (7.6 mmol/l),
increased blood urea nitrogen (BUN) (200 mg/dl) and creatininemia (2.5 mg/dl),
and decreased plasma bicarbonates level (HCO3-: 16 mmol/l; N: 27-30). However,
the plasma cortisol was high (66 microg/100 ml at 10:00 h; N: 8-15) and the ACTH
was normal (13 pg/ml, N: 10-60); there was a marked increase in plasma renin
activity (>37 ng/ml/h; N supine <3), active renin (869 pg/ml; N supine: 1.120),
aldosterone (>2000 pg/ml; N supine <150) and plasma AVP (20 pmol/l; N: 0.5-2.5).
The plasma ANH level was 38 pmol/l (N supine: 5-25). A urinary steroidogram
resulted in highly elevated tetrahydrocortisol (THF: 13.3 mg/24h; N: 1.4+/-0.8)
with no increase in tetrahydrocortisone (THE: 3.16 mg/24h; N: 2.7+/-2.0)
excretion, and with low THE/THF (0.24; N: 1.87+/-0.36) and alpha THF/THF (0.35;
N: 0.92+/-0.42) ratios. The number of mineralocorticoid receptors in mononuclear
leukocytes was in the lower normal range for age, while the number of
glucocorticoid receptors was reduced. Small-bowel resection in ileostomized
patients causes excessive fecal sodium losses and results in chronic sodium
depletion with contraction of the plasma volume and severe secondary
hyperaldosteronism. Nevertheless, this hyperaldosteronism may be associated with
hyponatremia and hyperkalemia suggesting PHA related to the major importance of
the colon for the absorption of sodium. In conclusion, this case report
emphasizes 1) the possibility of a syndrome of acquired PHA with severe
hyperkalemia after resection of the ileum and colon responding to oral salt
supplementation; 2) the major increase in AVP and the small increase in ANH; 3)
the strong increase in urinary THF with low THE/THF and alpha THF/THF ratios; 4)
the normal number of lymphocytic mineralocorticoid receptors outside the acute
episode.
PMID- 10195380
TI - The age of patients with thyrotoxicosis factitia in Italy from 1973 to 1996.
AB - Thyrotoxicosis factitia, a syndrome due to the surreptitious ingestion of excess
thyroid hormones, has generally been diagnosed in young or middle-aged women with
psychopathological disturbances. We reviewed all the cases seen at our
Institution over a 24-yr period, from 1973 to 1996. All 25 patients were women.
Analysis was restricted to 17 patients who were born and lived in Tuscany (our
region), since only these patients were distributed during the whole observation
period. Diagnosis of thyrotoxicosis factitia was based on the following
parameters: elevated serum total and/or free thyroid hormone levels, undetectable
serum thyrotropin levels, low/undetectable serum thyroglobulin concentration,
normal urinary iodine excretion, low/suppressed thyroidal radioactive iodine
uptake (RAIU), absence of goiter, absence of circulating anti-thyroid antibodies.
Surreptitious ingestion of thyroid hormone pill was eventually admitted by all
patients. Age at diagnosis was >50 yr in 7/17 patients (41%): 6 of them were
distributed in the period 1995-1996, and one in 1988. Patients older than 60 yr
were 5/17 (29%), all in the last two years of the period under investigation.
There was an increase in the age of patients with thyrotoxicosis factitia
(p=0.02), which lost a statistical significance when the patients of the 1995
1996 period were excluded from analysis (p=0.88). This study provides evidence of
an increased age of patients with thyrotoxicosis factitia in more recent years.
From a practical standpoint, our study suggests that thyrotoxicosis factitia
should be suspected and adequately looked for even in old patients with
thyrotoxicosis of inexplicable origin, especially in the absence of goiter and
thyroid autoimmune phenomena, and when common causes of low-RAIU hyperthyroidism,
such as a load with iodine-containing drugs or subacute thyroiditis, have been
excluded.
PMID- 10195381
TI - Three-month treatment with metformin or dexfenfluramine does not modify the
effects of diet on anthropometric and endocrine-metabolic parameters in abdominal
obesity.
AB - Abdominal obesity is connoted by hyperinsulinism and insulin insensitivity, a
trend toward glucose intolerance, hypoactivity of GH/IGF-I axis and alterations
of hypothalamo-pituitary-adrenal (HPA) axis. It has been hypothesized that
treatment with metformin (MET) and dexfenfluramine (DEX) could counteract those
endocrine-metabolic alterations. Thus, we studied the effects of 3-month
treatment with MET or DEX on anthropometric (BMI, WHR, FM and FFM), metabolic
(basal and OGTT-induced glucose) and hormonal variables (IGF-I, DHEA-S,
androstendione, testosterone, fT3, fT4, TSH, basal and OGTT-induced insulin) as
well as on blood pressure in 28 normotensive patients with abdominal obesity (OB,
3 M, 25 F; 47.5+/-1.5 yr [mean+/-SE], BMI 35.4+/-1.1 kg/m2, WHR 0.98+/-0.04 and
0.86+/-0.07, in M and F, respectively). All patients were on balanced hypocaloric
diet (1400 Kcal/day). Patients were randomly assigned to treatment with MET
(no.=10, 500 mg twice daily po) or DEX (no.=10, 15 mg thrice daily po) or placebo
(no.=8). Before treatment all groups had similar anthropometric, metabolic and
hormonal values. After 3-month treatment with MET, DEX or placebo, weight, BMI
and WHR reductions were similar in all groups (p<0.05 vs baseline in either
group). In each group FFM/FM ratio showed non significant trend toward increase.
No significant variations in metabolic and endocrine variables were recorded in
each group after 1 and 3-month treatment. However, glucose tolerance, OGTT
induced insulin response, glucose/insulin ratio showed a similar trend toward
improvement in all groups, while IGF-I, 24 h urinary cortisol, DHEA-S,
androstendione, testosterone, thyroid hormone and TSH levels did not show any
variation. Significant (p<0.02) and similar reductions of DBP, but not of SBP,
levels were found in all groups. In conclusion, our findings demonstrate that, at
least after 3-month treatment, metformin and dexfenfluramine do not modify the
effects of diet on anthropometric, metabolic and hormonal parameters as well as
on blood pressure in patients with abdominal obesity.
PMID- 10195382
TI - Headache and bilateral visual loss in a young hypothyroid Indian man.
AB - We describe the exceptional association of Vogt-Koyanagi-Harada syndrome (VKHS)
and hypothyroidism in a 29-year-old man of Indian heritage. VKHS is a rare
uveomeningoencephalitic syndrome with probably autoimmune pathogenesis.
Nontraumatic uveitis, aseptic meningoencephalitis, vitiligo, alopecia and
poliosis are the leading clinical features of VKHS. The reported patient
presented with bilateral visual loss and progressive frontal headache. VKHS was
diagnosed due to characteristic ophthalmological findings and the diagnosis of
aseptic meningitis. Due to the autoimmune pathogenesis, VKHS may be rarely
associated with other autoimmune disorders. Association of VKHS with autoimmune
thyroid disease has been described in the literature in three patients. In the
reported case hypothyroidism due to chronic autommune thyroiditis was diagnosed
in association with VKHS. Routinely determination of thyroid function in patients
with VKHS is recommended.
PMID- 10195383
TI - Short- and long-term effect of a long-acting somatostatin analogue, lanreotide
(SR-L) on metastatic gastrinoma.
AB - Medical treatment is the elective therapy for patients with gastrinoma when the
tumor is not found at surgery or is unresectable or when there is a metastatic
disease. H2-blockers and omeprazol are able to control gastric acid secretion
and, in addition, somatostatin analogues decrease gastrin levels. A new long
acting and slow release formulation of a somatostatin analogue (lanreotide, SR-L)
has been developed. We treated two patients suffering from gastrinoma, total
gastrectomy and hepatic metastases with 30 mg intramuscular injections of SR-L
every 15 and 10 days, respectively, for a seven-month period. After the
treatment, gastrin levels decreased from 35,494 and 15,086 ng/l to 3,211 and 167
ng/l (92 and 98% below pre-treatment levels) in case 1 and 2 respectively, with a
relief of symptoms and no side effects.
PMID- 10195384
TI - Appearance of anti TSH-receptor antibodies and clinical Graves' disease after
radioiodine therapy for hyperfunctioning thyroid adenoma.
AB - Radioiodine treatment use is frequent in patients with benign hyperfunctioning
thyroid diseases and the side-effects are rare. In this paper we described the
appearance of TSH-receptor antibodies and the concomitant development of
persistent hyperthyroidism in a patient with hyperfunctioning thyroid adenoma
after 131I treatment. A 70-year-old man presented a hyperfunctioning thyroid
adenoma with suppressed uptake in the adjacent normal gland. Antibodies against
the thyroglobulin (TgAb), thyroid peroxidase (TPOAb) and TSH-receptor (TRAb) were
absent. One year after remission by radioiodine therapy the patient developed
severe and persistent hyperthyroidism associated with diffuse 131I uptake in the
gland. TgAb and TPOAb remained absent, but TRAb were present. Although
spontaneous development of Graves' disease cannot be excluded, the time sequence
and the negative familial and personal history for autoimmune diseases suggest a
possible connection between the two phenomena. The release of TSH-receptor
antigen from follicular cells damaged by 131I may have triggered the autoimmune
response turning a toxic nodular goiter patient into a Graves' disease patient.
PMID- 10195385
TI - In vivo imaging of insulitis in autoimmune diabetes.
PMID- 10195386
TI - Orientation variance as a quantifier of structure in texture.
AB - I consider how structure is derived from texture containing changes in
orientation over space, and propose that multi-local orientation variance (the
average orientation variance across a series of discrete images locales) is an
estimate of the degree of organization that is useful both for spatial scale
selection and for discriminating structure from noise. The oriented textures used
in this paper are Glass patterns, which contain structure at a narrow range of
scales. The effect of adding noise to Glass patterns, on a structure versus noise
task (Maloney et al., 1987), is compared to discrimination based on orientation
variance and template matching (i.e. having prior knowledge of the target's
orientation structure). At all but very low densities, the variance model
accounts well for human data. Next, both models' estimates of tolerable
orientation variance are shown to be broadly consistent with human discrimination
of texture from noise. However, neither model can account for subjects' lower
tolerance to noise for translational patterns than other (e.g. rotational)
patterns. Finally, to investigate how well these structural measures preserve
local orientation discontinuities, I show that the presence of a patch of
unstructured dots embedded in a Glass pattern produces a change in multi-local
orientation variance that is sufficient to account for human detection (Hel Or
and Zucker, 1989). Together, these data suggest that simple orientation
statistics could drive a range of 'texture tasks', although the dependency of
noise resistance on the pattern type (rotation, translation, etc.) remains to be
accounted for.
PMID- 10195387
TI - Spatial frequency and visual persistence: cortical reset.
AB - Psychophysical studies show that the duration of visual persistence increases
with spatial frequency of gratings. Previous theories ascribe this finding to
differences between the spatial and temporal properties of sustained and
transient pathways. This paper proposes an alternative account that explains
persistence as a side-effect of excitatory feedback in neural circuits for
contour extraction. Mechanisms to break excitatory feedback include inhibitory
reset signals at stimulus offset. Simulations demonstrate how gratings with lower
spatial frequency generate stronger inhibitory reset signals, thereby resulting
in shorter persistence for lower spatial frequencies. Additional simulations
account for interactions of spatial frequency with stimulus duration, effects of
adaptation, and properties of residual traces, as opposed to visual persistence.
PMID- 10195388
TI - Sustained focal attention and peripheral letter recognition.
AB - Topographic characteristics of peripheral letter recognition were investigated
using a sustained attention paradigm to clarify whether its deployment in the
visual field is equally easy in all eight tested locations at 7.5 deg
eccentricity. Target size (36 arcmin) was clearly above threshold, so that
letters were easily recognized at long durations (> 500 ms). In the main
experiment, they were displayed for an individually determined duration of 66 to
167 ms. Six of twelve normally sighted subjects were in their twenties, the
others in their fifties. The target location was cued (1 s), and after 2.5-4 s
delay, a target was displayed. The results provide strong evidence that
performance depended significantly on location and subject. All spatial
characteristics showed anisometry, and most showed vertical asymmetry of either
sign. Performance was always best on the horizontal meridian. None of the results
correlated with subject age. These findings also show that in disfavored
locations, performance is limited by deploying attention there, not by holding it
there. Consequently, in low vision rehabilitation after binocular central field
loss, the choice of a preferred retinal locus for 'eccentric viewing' can be
limited by an attentional factor that is unrelated to the eye disease.
PMID- 10195389
TI - The Catch model: a solution to the problem of saliency in facial features.
AB - The goal of the present paper is to propose a solution to the 'saliency problem'
which has been raised in regard to Rakover and Cahlon's (1989) Catch model for
identifying a previously seen target face (Ft). In contrast to real life
situations, the Catch model assigned the same weight to different facial
dimensions and values. Mathematical proofs, reanalyses of the results of three
experiments reported in Rakover and Cahlon, and the analysis of the results of a
new experiment show that this proposal expands and improves the Catch model.
PMID- 10195390
TI - Factors limiting peripheral pattern discrimination.
AB - Previous reports indicate that some foveally discriminable compound gratings are
indiscriminable in peripheral vision, even when they are scaled by the ratio of
peripheral to foveal grating acuity. To determine the stimulus properties that
limit peripheral discrimination, we used Gaussian derivatives of various orders.
These patterns are spatially localized and have intrinsic even or odd symmetry.
Our results show that certain odd symmetric patterns are discriminable in the
periphery, while others are not. Furthermore, certain even symmetric patterns are
not peripherally discriminable. These data are consistent with three limitations
on peripheral pattern discrimination: (1) Patterns that produce different maximum
neural responses will be peripherally discriminable. (2) Positional uncertainty
and undersampling degrade discrimination of high spatial frequency patterns in
the periphery. (3) Patterns generating substantial neural activity within a
constrained region are processed as textures in peripheral vision so that pattern
details within that region are no longer available for discrimination. A neural
model incorporating inhibition of simple cells by complex cells implements a
transition between contour analysis and texture analysis in peripheral vision and
explains the experimental data.
PMID- 10195391
TI - Effects of parametric manipulation of inter-stimulus similarity on 3D object
categorization.
AB - To explore the nature of the representation space of 3D objects, we studied human
performance in forced-choice categorization of objects composed of four geon-like
parts emanating from a common center. Two categories were defined by prototypical
objects, distinguished by qualitative properties of their parts (bulging vs waist
like limbs). Subjects were trained to discriminate between the two prototypes
(shown briefly, from a number of viewpoints, in stereo) in a 1-interval forced
choice task, until they reached a 90% correct-response performance level. After
training, in the first experiment, 11 subjects were tested on shapes obtained by
varying the prototypical parameters both orthogonally (ORTHO) and in parallel
(PARA) to the line connecting the prototypes in the parameter space. For the
eight subjects who performed above chance, the error rate increased with the
ORTHO parameter-space displacement between the stimulus and the corresponding
prototype; the effect of the PARA displacement was weaker. Thus, the parameter
space location of the stimuli mattered more than the qualitative contrasts, which
were always present. To find out whether both prototypes or just the nearest one
to the test shape influenced the decision, in the second experiment we varied the
similarity between the categories. Specifically, in the test stage trials the
distance between the two prototypes could assume one of three values (FAR,
INTERMEDIATE, and NEAR). For the 13 subjects who performed above chance, the
error rate (on physically identical stimuli) in the NEAR condition was higher
than in the other two conditions. The results of the two experiments contradict
the prediction of theories that postulate exclusive reliance on qualitative
contrasts, and support the notion of a representation space in which distances to
more than one reference point or prototype are encoded (Edelman, 1998).
PMID- 10195392
TI - Characterization of human skin-derived CD1a-positive lymph cells.
AB - The phenotype and function of CD1a+ lymph cells is of considerable interest. By
means of microsurgical lymph cannulation human lymph derived from normal skin was
sampled. Cells were isolated and processed for immunocytochemistry, electron
microscopy, flow cytometry and functional assays. The majority of the cells,
(62%), were T cells. The other cells comprised CD1a+ cells (7%),
monocytes/macrophages (8%), and B cells (1%); the remainder were erythrocytes or
uncharacterized cells. The CD1a+ cells reacted with antibodies against protein S
100, HLA-DR, the Lag antigen, CD4, CD11a, CD11b, CD18, CD25, CD40, CD54, CD80 and
CD86. Interestingly, a small prolow portion the of CD1a+ cells (about 5%) reacted
with an antibody to CD14. The CD1a+ cells did not react with an antibody against
human follicular dendritic cells nor were they CD19-, CD23-, E-cadherin- or
factor XIIIa-positive. Both allogenic and antigen-specific T cell proliferation
stimulated by antigen-presenting lymph cells were strongly inhibited by adding
anti-CD80 and anti-CD86 antibodies. By electron microscopy Birbeck granules were
detected in only 22% of the CD1a+ lymph cells and these cells exhibited an
extensive ruffling of the surface. These findings demonstrate that CD1a+ lymph
cells, which do not express the dermal dendritic cell marker factor XIIIa,
resemble dendritic cells formerly designated as 'veiled' as well as lymphoid
dendritic cells, suggesting that after migration to the regional lymphoid organs,
Langerhans cells form a more differentiated population of dendritic cells
specialized in sensitizing T lymphocytes. Our results add further support to the
view that resident Langerhans cells may be precursors of lymphoid dendritic cells
acquiring the final phenotype in the microenvironment of the lymph node.
PMID- 10195393
TI - Identification and characterization of multiple forms of tryptase from human mast
cells.
AB - Mast cell tryptase purified from human adult skin (AS), adult lung (AL) and
newborn foreskin (NS) with a monoclonal antitryptase B2 immunoaffinity Sepharose
column was further fractionated by HPLC using a Mono-S cation exchange column at
pH 6.5. Tryptases exhibited two clearly separated major fractions, both of which
also revealed at least two overlapping peaks. Native tryptase molecules from skin
consisted of two diffuse protein bands in SDS-PAGE at about 31 and 35 kDa,
whereas those from lung usually exhibited a predominant diffuse band at about 29
kDa. The forms of tryptases separated by Mono-S HPLC gave a different banding
pattern in SDS-PAGE. Tryptase from NS exhibited chromatographic peaks that each
showed Mr values approximately 1-3 kDa higher than those of tryptase from AS. By
gel filtration, the Mr values for native major fractions of tryptases derived
from AS and AL were 178 kDa and 141 kDa, respectively. After carbohydrate removal
by glycanase, the observed differences in Mr values in SDS-PAGE reduced to two
similar sharp bands of Mr approximately 28 kDa and 30 kDa for all tryptase
preparations. AS and AL tryptases and their subfractions exhibited similar enzyme
kinetic values and similar immunoreactivities in a tryptase immunoassay.
Inactivation rates at physiologic ionic strength were similar for both AL and AS
tryptases. The results show the enzymatic and antigenic similarity between lung
and skin tryptases, and suggest that tryptase is stored mainly as beta-tryptase
in human mast cells. Tryptase immunoassay measures similarly both lung and skin
tryptases and, thus, this assay is suitable for detection of mast cell
activation, in contrast to assays for other proteinases of mast cells, e.g.
chymase, cathepsin G and carboxypeptidase, that are present in MC(TC) cells
mainly in skin only.
PMID- 10195394
TI - Increase in telomerase activity during progression of melanocytic cells from
melanocytic naevi to malignant melanomas.
AB - During successive cell divisions of mortal cells the length of the telomeres
(TTAGGG repeats in vertebrates) at the end of chromosomes decreases. It has been
suggested that this process is responsible for cellular senescence. Expression of
the ribonucleoprotein telomerase appears to prevent shortening of telomeres in
germ-line cells and cancer cells. The purpose of this study was to investigate
telomerase activity in melanocytic lesions and its possible role in the multi
step tumor progression model of malignant melanoma. To quantify the level of
telomerase activity both in cultured cells and in fresh tissue samples the TRAP
(telomeric repeat amplification protocol) ELISA was used. Eight cell lines of
malignant melanoma, 3 primary cultures of fibroblasts, 36 melanocytic naevi, 5
atypical melanocytic naevi, 3 Spitz's naevi, 31 primary malignant melanomas and
13 metastases of malignant melanomas were investigated. Also 34 samples of skin
(22 samples of perilesional skin and 12 samples of normal skin) were analysed. In
our experiments all melanoma cell lines were strongly positive, whereas in
fibroblasts telomerase activity could not be detected. Of the primary melanomas
and metastatic melanomas, 90.3% and 92.3%, respectively, were strongly positive,
and of the atypical melanocytic naevi, 80% were positive. Of the 36 common
melanocytic naevi only 10 (27.7%) expressed weak telomerase activity and of the
34 samples of human skin, 4 (11.7%) expressed very weak telomerase activity. Our
results indicate that telomerase activity increases from benign melanocytic naevi
to atypical naevi and further to malignant melanoma and metastatic melanoma
cells, and therefore may play a role in tumour initiation and progression.
PMID- 10195395
TI - Quantification of epidermal cell populations in the centre and margin of stable
psoriatic plaques.
AB - The histological picture of psoriasis has been studied extensively. Several
authors have investigated the differences between the centre and the margin of
spreading plaques, because the margin is of great pathogenic interest as lesions
enlarge by centrifugal expansion. However, little is known about the differences
between the centre and the margin of stable plaques. In the present study we
investigated quantitatively the differences between the centre and margin of
stable psoriatic plaques with respect to differentiation, inflammation and
proliferation. To quantify these parameters, we used flow cytometry. From nine
patients with nonspreading, stable psoriasis, we obtained punch biopsies from the
centre and from the lesional margin of a plaque, and performed a flow cytometric
assessment, using the markers keratin 10 for differentiation, vimentin for
inflammation, and TO-PRO-3 iodide for proliferation. We found that the
quantitative parameters showed a large interindividual variability, and that
there was no significant difference in the quantitative parameters for
inflammation and proliferation between the centre and margin of stable plaques.
However, the percentage of differentiated cells was significantly higher in the
margin than in the centre. We conclude that there is a great heterogeneity within
stable psoriatic plaques with respect to differentiation, inflammation and
proliferation, but further quantitative studies are needed to substantiate the
pathogenic relevance of the significant difference in keratinization between the
centre and the margin of stable psoriatic plaques.
PMID- 10195396
TI - Cultured fibroblasts from chronic diabetic wounds on the lower extremity (non
insulin-dependent diabetes mellitus) show disturbed proliferation.
AB - Patients with diabetes mellitus experience impaired wound healing often resulting
in chronic foot ulcers. Hospital discharge data indicate that 6-20% of all
diabetic individuals hospitalized (mostly with type 2 diabetes) have a lower
extremity ulcer. Maintaining glucose levels at acceptable levels (below 10
mmol/l) is considered to be an important part of the clinical treatment, but the
exact mechanism by which diabetes delays wound repair is not yet known. We
studied this phenomenon by determining the potential of fibroblasts isolated from
the ulcer sites of four patients with non-insulin-dependent diabetes mellitus to
proliferate in vitro. Controls were fibroblasts isolated from normal skin of the
upper leg of five healthy age-matched volunteers and of six non-insulin-dependent
diabetes patients. Proliferative capacity was analysed by evaluation of plates
after trypsinization and [3H]thymidine incorporation. Fibroblast morphology was
studied by light and transmission electron microscopy. Diabetic ulcer
fibroblasts, measured by [3H]thymidine incorporation, proliferated significantly
more slowly than the nonlesional control fibroblasts (P < 0.00047) and age
matched control fibroblasts (P < 0.00003). After culturing the fibroblasts for a
prolonged period in high-glucose (27.5 mM) and low-glucose (5.5 mM, i.e.
physiological) medium, this difference in proliferation rate between diabetic
ulcer fibroblasts and nonlesional diabetic fibroblasts remained (P < 0.0001 for
high-glucose and P < 0.0009 for low-glucose on day 7). Fibroblast proliferation
in all three groups was slightly lower in high-glucose than in low-glucose
medium, although not significantly at any time-point. Light microscopy showed
diabetic ulcer fibroblasts to be large and widely spread. Transmission electron
microscopy of cultured diabetic ulcer fibroblasts and nonlesional diabetic skin
fibroblasts revealed a large dilated endoplasmic reticulum, a lack of
microtubular structures and multiple lamellar and vesicular bodies. These results
show a diminished proliferative capacity and abnormal morphology of fibroblasts
derived from diabetic ulcers of non-insulin-dependent diabetes patients.
PMID- 10195397
TI - Finasteride is the main inhibitor of 5alpha-reductase activity in microdissected
dermal papillae of human hair follicles.
PMID- 10195398
TI - The SCID-hu xenogeneic transplantation model allows screening of anti-psoriatic
drugs.
PMID- 10195399
TI - Early diagnosis and the clinical genetics of Alzheimer's disease.
AB - Alzheimer's disease (AD) has a significant genetic background manifested as
autosomal dominant inheritance in some early-onset families and as familial risk
in late-onset cases. Three genes responsible for early-onset autosomal dominant
AD have been identified, and one gene, apolipoprotein E, has been confirmed as a
susceptibility gene for late-onset forms of the disorder. These findings raise
the possibility of genetic testing, either for early diagnosis or prediction. For
early-onset autosomal dominant AD genetic testing will have a limited but useful
role in confirming diagnosis in established cases and in predictive counselling
for relatives; a situation analogous to that for Huntington's disease. For late
onset AD significant problems remain to be overcome before the advances in
molecular genetics have a direct clinical application
PMID- 10195400
TI - Early diagnosis of dementia: which tests are indicated? What are their costs?
AB - Dementia is reversible in a minority of patients, and these should be diagnosed
but without subjecting the majority with irreversible disease to an excessive set
of investigations. Should a battery of ancillary investigations be performed
routinely in dementia? Or can these tests be carried out as clinically indicated?
Three arguments are important to answer this question. (a) Reversible dementia is
rare: about 1% of cases. (b) If the clinical criteria for diagnosing primary
degenerative disease are used consistently, the results of investigations can be
predicted with sufficient accuracy, except those of blood tests. (c) Treatment of
reversible dementia has the best results in its most frequent causes: depression
and drug intoxication; however, treatment of medical and surgical causes of
dementia may also be effective. Based on these three considerations, we propose
the following guideline in the setting of a memory clinic: to perform blood tests
in every patient with dementia, but also to perform other tests, such as
electroencephalography (EEG) and computed tomography (CT), as clinically
indicated.
PMID- 10195401
TI - Validation of a mail questionnaire for parkinsonism in two languages (German and
Italian).
AB - As part of a larger epidemiological study [Neuro-Epidemiology Project South-Tyrol
(NEPT)], we investigated the accuracy of a mail questionnaire for parkinsonism in
two languages (German and Italian). We administered the instrument to 40 randomly
selected subjects with parkinsonism (Italian-speaking, n = 20; German-speaking, n
= 20), attending our Parkinson's disease clinic regularly. Each patient was
matched by age, sex and language with a subject without parkinsonism residing in
the same South-Tyrol Province in Northern Italy. Subjects free of parkinsonism
were recruited randomly from two group practices collaborating in the NEPT study.
A questionnaire containing nine symptom questions and two additional questions
about the patient's diagnosis of parkinsonism and/or treatment was mailed to each
subject's home. Forty subjects with parkinsonism and 36 without parkinsonism
participated in the study. All nine symptom items showed significant differences
between affected and unaffected individuals. A combination of any three questions
yielded the best balance between sensitivity (95%) and specificity (89%). There
were no differences between the German- and Italian-speaking groups. We
demonstrated the usefulness of a simple questionnaire for validating the
diagnosis of parkinsonism irrespective of the primary native language.
PMID- 10195402
TI - Serum soluble adhesion molecules in multiple sclerosis: raised sVCAM-1, sICAM-1
and sE-selectin in primary progressive disease.
AB - Leucocyte invasion into the central nervous system in multiple sclerosis (MS) is
complex, involving T-cell/endothelium interaction dependent upon initial adhesion
mediated by molecules such as E-selectin, L-selectin, intracellular adhesion
molecule-1 (ICAM-1) and vascular cell adhesion molecule-(VCAM-1). Circulating
levels of these can be measured by sensitive enzyme-linked immunoassay (ELISA)
techniques. To assess whether serum concentrations of soluble adhesion molecules
vary across the spectrum of patients with relapsing-remitting (RR), secondary
progressive (SP) and primary progressive (PP) MS, we measured circulating levels
of soluble (s)E-selectin, sL-selectin, sICAM-1 and sVCAM-1 in serum obtained from
78 PPMS patients, 71 patients with RRMS, 65 patients with SPMS and 66 patients
with other neurological disease using commercially available ELISA systems.
Levels of serum sVCAM-1 were significantly elevated in PPMS compared with RRMS in
remission (P = 0.0001) and in relapse (P = 0.0001), whilst sICAM-1 was
significantly elevated in PPMS compared with all other MS groups (vs SPMS, P =
0.006; vs RRMS in relapse, P = 0.003; vs RRMS in remission, P = 0.0001). Serum sE
selectin levels were significantly higher in PPMS compared with all other groups
except inflammatory neurological disease (IND) [vs SPMS, P = 0.029; vs RRMS in
relapse, P = 0.002; vs RRMS in remission, P = 0.001; vs non-inflammatory
neurological disease (NIND), P = 0.002; vs IND, P = 0.076]. In PPMS there was no
correlation between levels of any adhesion molecule and disability or disease
duration. These results provide evidence for significant immunological
heterogeneity in MS and suggest that different leucocyte/endothelial cell
interactions may be active in various MS subgroups. It also challenges the
hypothesis that PPMS is a less inflammatory form of the disease.
PMID- 10195403
TI - Clinical outcome of sural nerve biopsy: a retrospective study.
AB - Sural nerve biopsy is a valuable tool in establishing the diagnosis and
investigating the underlying causes of peripheral neuropathies. Few
investigations have been carried out in which the sequelae of this procedure have
been described systematically. We studied the short-term adverse reactions in 110
patients and the long-term outcome of sural nerve biopsy in a subgroup of 54
patients after 5-32 months. Long-lasting sensory deficits were reported in 93%,
dysaesthesia in 19% and mild persistent pain in 33% of the 54 patients. No
significant differences were found between patients followed for 1-2 years and
those followed for more than 2 years in the frequency and distribution of
hypaesthesia and anaesthesia. However, dysaesthesia was less frequent after more
than 2 years (6/32 vs 1/16), and persistent pain completely subsided within our
observation period. We conclude that disabling sequelae regress and finally
subside over time. If we assume that returning for follow-up visits may cause
bias towards more severely affected patients, the overall prognosis may be even
better.
PMID- 10195404
TI - A comparison of the sensitivity of monthly unenhanced and enhanced MRI techniques
in detecting new multiple sclerosis lesions.
AB - In this longitudinal study, the sensitivities of three magnetic resonance imaging
techniques for detecting the appearance of new lesions in multiple sclerosis (MS)
were evaluated and compared. Dual-echo conventional spin-echo (CSE), fast fluid
attenuated inversion recovery (fast-FLAIR) and post-contrast T1-weighted scans
were obtained on four occasions, each separated by 28 days, from 18 patients with
relapsing-remitting MS using a 1.5-T machine. New lesions seen using each
sequence during the follow-up were counted by agreement by four observers in two
stages (stage 1: random review of complete sets of scans from each technique;
stage 2: side-by-side review with a 'retrospective' count of new lesions). At
stage 1, 1.44 new lesions per patient per month were detected on CSE scans, 1.88
on fast-FLAIR (31% more than CSE) and 2.07 on post-contrast T1-weighted scans
(44% more than CSE) (P = 0.03). Differences were, however, reduced after stage 2:
fast-FLAIR detected 29% and post-contrast T1-weighted scans detected 31% more new
lesions than CSE(P = 0.08). The combination of fast-FLAIR and post-contrast scans
detected 144 new lesions, whilst the usual combination of CSE and post-contrast
scans detected 133 new lesions. This study indicates that enhanced MRI remains
the most sensitive method for detecting 'active' lesions in MS and that fast
FLAIR may be used when monitoring short-term disease activity in MS, either
natural or modified by treatment.
PMID- 10195405
TI - Autosomal recessive type II hereditary motor and sensory neuropathy with
acrodystrophy.
AB - A family is described with presumed autosomal recessive inheritance in which
three siblings developed a progressive neuropathy that combined limb weakness and
severe distal sensory loss leading to prominent mutilating changes.
Electrophysiological and nerve biopsy findings indicated an axonopathy. The
disorder is therefore classifiable as type II hereditary motor and sensory
neuropathy (HMSN II). The clinical features differ from those reported in
previously described cases of autosomal recessive HMSN II. This disorder may
therefore represent a new variant.
PMID- 10195406
TI - Neuropsychological follow-up of 12 patients with neuro-Behcet disease.
AB - We analyzed the data obtained from neuropsychological evaluations of 12 neuro
Behcet Disease (NBD) patients who had been followed up for 35.6+/-23.7 months
with successive neuropsychological testing by a comprehensive battery. Memory
impairment, which seems to stem basically from a retrieval deficit, was the major
finding in this series. The most severely affected memory process was delayed
recall, being impaired in all of the patients in the verbal and/or visual
modalities. This was followed closely by an impairment in the process of
acquisition and storage. In addition to the memory impairment, a "clinical
impression of personality change" toward either disinhibition or apathy was seen
in 8 of the 12 patients. Attention deficit was of the third highest frequency and
was present in 7 patients, followed by deficits of executive functions of frontal
system which were present in 5. Other cognitive domains were rarely involved.
Neuropsychological status deteriorated insidiously, regardless of the
neurological attacks during the follow-up period in most of the patients.
Furthermore, our observations also showed the presence of cognitive decline prior
to detectable lesions on CT or MRI, emphasizing the need for neuropsychological
testing in NBD patients. The late stages of the disease seem to be reflected in
MRI as an enlargement of the third ventricle and atrophy of the upper brainstem,
which could be compatible with memory loss. Our series, a rather selected group,
suggests that NBD can be associated with a special pattern of cognitive deficit,
especially memory loss and personality change. The designation of any specific
neurobehavioral syndrome for NBD, however, awaits further study.
PMID- 10195407
TI - Paroxysmal kinesigenic choreoathetosis: a report of 26 patients.
AB - Paroxysmal kinesigenic choreoathetosis (PKC) is a neurological condition which
results in abnormal involuntary movements that are precipitated by sudden
movement. Because of its rarity, large case series of PKC have not been
published. We studied 26 patients with PKC, which represents the largest series
thus reported. We reviewed our cases with respect to attack characteristics,
aetiology, family history, and treatment response. Our population consisted of 23
men and 3 women. Seven patients had a family history of paroxysmal dyskinesia.
None of our patients had clear evidence of symptomatic PKC. Two-thirds of our
patients had attacks lasting between 30-60 s, and over one-half experienced one
to ten attacks per day. Attack distribution varied widely, and most experienced
pure dystonia rather than choreodystonic movements. Most patients responded very
well to anticonvulsant therapy. We also report the PET results from two of our
patients and Bereitschaftspotential abnormalities recorded from two others.
PMID- 10195408
TI - Emotionally evoked changes in cerebral hemodynamics measured by transcranial
Doppler sonography.
AB - The cerebral representation of emotions has previously been investigated by the
study of patients with local brain damage, experiments with selective stimulation
of only one hemisphere, and more recently by imaging techniques such as positron
emission tomography or magnetic resonance imaging measuring local cerebral blood
flow. We investigated the mean flow velocity (FVmean) in the middle cerebral
artery (MCA) by transcranial Doppler sonography during emotional stimulation with
video scenes in 24 healthy test persons. The videos consisted of an erotic scene
and a violent scene shown in contrast to a calming scene. Blood pressure, heart
rate, and breathing frequency were monitored continuously by noninvasive
measurement. FVmean increased during the erotic scene to 108.5+/-11.9% (P < 0.05)
of the baseline value in the right MCA and to 109.0+/-10.6% (n.s.) in the left
MCA. During the violent scene FVmean reached 109.0+/-8.7% (P < 0.05) on the right
side and 108.1+/-13.0% (n.s.) on the left side. The FVmean time course showed a
close relationship to the video sequence. During scenes involving great tension
FVmean showed a plateaulike state and peaked during sudden actions. Blood
pressure, heart rate, and respiratory rate showed no significant changes.
However, we observed a tendency towards lower heart rates (lowest value 94.5+/
13.6%) during the erotic scene and two peaks (103.2+/-13.3%, 104.8+/-16.8%)
coinciding with sudden violent actions. The significant increase in FVmean in the
right MCA supports the theory of a right hemisphere dominance for the processing
of emotions.
PMID- 10195409
TI - Craniofacial pain followed by scalp necrosis and stroke. An unusual presentation
of the primary antiphospholipid syndrome.
PMID- 10195410
TI - Atypical multiple sclerosis presenting as chronic-progressive encephalomyelitis
with polyneuritis and recurrent aseptic meningitis.
PMID- 10195411
TI - Blink reflex in trigeminal hypoesthesia caused by a pontine demyelinating lesion.
PMID- 10195412
TI - Pathological correlate of the slitlike changes on MRI at the putaminal margin in
multiple system atrophy.
PMID- 10195413
TI - Cerebral venous thrombosis: recurrence with fatal course.
PMID- 10195414
TI - Shoulder hopping on giants.
PMID- 10195415
TI - Moving from Zurich to Vienna--up or down?
PMID- 10195416
TI - The IMP and European molecular biology: moving the centre eastwards. Institute of
Molecular Pathology.
PMID- 10195417
TI - Max, the Vienna Biocenter and other 'spin-off'.
PMID- 10195418
TI - The functions of breast cancer susceptibility gene 1 (BRCA1) product and its
associated proteins.
AB - About half of the familial breast cancer cases are found to bear mutations in the
breast cancer susceptibility gene 1 (BRCA1). The majority of BRCA1 mutations
produce a truncated protein and BRCA1-associated breast tumors exhibit a number
of defined tumor phenotypes. The function of BRCA1 has been examined in gene
knockout mice in which the nullizygous mice die early in utero, but this
lethality can be partially rescued by a nullizygous p53 mutation. Wild-type BRCA1
protein binds to a number of cellular proteins, including DNA repair protein
Rad51, tumor suppressor p53, RNA polymerase II holoenzyme, RNA helicase A, CtBP
interacting protein, c-myc, BRCA1-associated RING domain protein (BARD1), BRCA2
protein, etc. These proteins likely mediate the involvement of BRCA1 in DNA
repair, transcriptional transactivation, and cell cycle control. Overall, BRCA1
protein may act as a converging vehicle for cell regulatory proteins to associate
with. Therefore, mutations in BRCA1 may affect the composition of these complexes
on which dysregulation of cellular functions with eventual development of
malignancy is expected.
PMID- 10195419
TI - Lymphocyte antigen receptor signal integration and regulation by the SHC adaptor.
AB - The Shc adaptor protein transduces signals from transmembrane receptors to the
Ras pathway of cell activation by providing binding sites for the recruitment to
the submembrane compartment of the Grb2/Sos G-nucleotide exchange complex. The
need for Shc in this process is however unclear since Grb2 can be recruited
directly to phosphotyrosine containing membrane receptors through its src
homology-2 domain. Evidence from studies in lymphocytes indicates that Shc is
multifunctional and is involved in the integration of independent signals to the
Ras pathway. Furthermore, Shc may be a key control point at which signaling can
be modulated both by interfering signals and by feedback mechanisms. Here we
review recent literature to support these functions for Shc.
PMID- 10195420
TI - New insights into signal recognition and elongation arrest activities of the
signal recognition particle.
AB - The signal recognition particle (SRP), a ubiquitous cytoplasmic ribonucleoprotein
particle, plays an essential role in promoting co-translational translocation of
proteins into the endoplasmic reticulum. Here, we summarise recent progress made
in the understanding of two essential SRP functions: the signal recognition
function, which ensures the specificity, and the elongation arrest function,
which increases the efficiency of translocation. Our discussion is based on
functional data as well as on atomic structure information, both of which also
support the notion that SRP is a very ancient particle closely related to
ribosomes. Based on the significant increase of knowledge that has been
accumulating on the structure of elongation factors and on their interactions
with the ribosome, we speculate about a possible mechanism of the elongation
arrest function.
PMID- 10195421
TI - Being at the right place at the right time: the role of nuclear transport in
dynamic transcriptional regulation in yeast.
AB - As a consequence of compartmentalization in eukaryotic cells, the transcriptional
response to extracellular stimuli requires signals to be transmitted from the
cytoplasm to the nucleus. Thus, nuclear import and export of signal transduction
and transcription factors provide an important level of transcriptional control
in eukaryotes. Recent investigations have illustrated the importance of this
control for dynamic gene expression, as will be discussed on transcriptional
activators and repressors (Mac1p, Mig1p, Msn2p/4p, Swi5p) and protein kinases
(Hog1p, Sty1/Spc1, protein kinase A).
PMID- 10195422
TI - Plectin: a cytolinker by design.
AB - Plectin is a cytoskeletal protein of >500 kDa that forms dumbbell-shaped
homodimers comprising a central parallel alpha-helical coiled coil rod domain
flanked by globular domains, thus providing a molecular backbone ideally suited
to mediate the protein's interactions with an array of other cytoskeletal
elements. Plectin self-associates and interacts with actin and intermediate
filament cytoskeleton networks at opposite ends, and it binds at both ends to the
hemidesmosomal transmembrane protein integrin beta-4, and likely to other
junctional proteins. The central coiled coil rod domain can form bridges over
long stretches and serves as a flexible linker between the structurally diverse N
terminal domain and the highly conserved C-terminal domain. Plectin is also a
target of p34cdc2 kinase that regulates its dissociation from intermediate
filaments during mitosis.
PMID- 10195423
TI - Regulation of the sea urchin early H2A histone gene expression depends on the
modulator element and on sequences located near the 3' end.
AB - Transcription of the sea urchin early histone genes occurs transiently during
early cleavage, reaching the maximum at the morula stage and declining to an
undetectable level at the gastrula stage. To identify the regulatory elements
responsible for the timing and the levels of transcription of the H2A gene, we
used promoter binding studies in nuclear extracts and microinjection of a CAT
transgene driven by the early H2A promoter. We found that morula and gastrula
nuclear proteins produced indistinguishable DNase I footprint patterns on the H2A
promoter. Two sites of interactions, centred on the modulator/enhancer and on the
CCAAT box respectively, were detected. Deletion of the modulator or coinjection
of an excess of modulator sequences severely affected the expression of two
transgenes driven by the enhancer-less and modulator-containing H2A promoter.
Finally, a DNA fragment containing 3' coding and post-H2A spacer sequences, where
upon silencing three micrococcal nuclease hypersensitive sites were previously
mapped, specifically repressed at the gastrula stage the expression of the
transgene driven by the H2A promoter. These results indicate that the modulator
is essential for the expression of early H2A gene and that sequences for
downregulation are localized near the 3' end of the H2A gene.
PMID- 10195424
TI - A ribosomal orphon sequence from Xenopus laevis flanked by novel low copy number
repetitive elements.
AB - We have used a differential cloning approach to isolate ribosomal/non-ribosomal
frontier sequences from Xenopus laevis. A ribosomal intergenic spacer sequence
(IGS) was cloned and shown not to be physically linked with the ribosomal locus.
This ribosomal orphon contained the IGS sequences found immediately downstream of
the 28S gene and included an array of enhancer repetitions and a non-functional
spacer promoter. The orphon sequence was flanked by a member of the novel 'Frt'
low copy repetitive element family. Three individual Frt repeats were sequenced
and all members of this family were shown to lie clustered at two chromosomal
sites, one of which contained the ribosomal orphon. One of the Frt elements
contained an insertion of 297 bp that showed extensive homology to sequences
within at least three other Xenopus genes. Each homology region was flanked by
members of the T2 family of short interspersed repetitive elements, (SINEs), and
by its target insertion sequence, suggesting multiple translocation events. The
data are discussed in terms of the evolution of the ribosomal gene locus.
PMID- 10195425
TI - Characterization of the transcription factor MTF-1 from the Japanese pufferfish
(Fugu rubripes) reveals evolutionary conservation of heavy metal stress response.
AB - The pufferfish Fugu rubripes was recently introduced as a new model organism for
genomic studies, since it contains a full set of vertebrate genes but only 13% as
much DNA as a mammal. Fugu genes tend to be smaller and densely spaced due to
shortening of introns and intergenic spacers. We isolated the Fugu gene for the
metal-responsive transcription factor MTF-1 (MTF1), a mediator of heavy metal
regulation and oxidative stress response previously characterized in mammals. In
addition, most of the cDNA sequence was also determined. The 780 amino acid MTF-1
protein of Fugu is very similar to that of mouse and human, with 90% amino acid
identity in the DNA binding zinc finger domain and 57% overall identity.
Expression of the pufferfish cDNA in mammalian cells shows that Fugu MTF-1 has
the same DNA binding specificity as its mammalian counterpart and also induces
transcription in response to zinc and cadmium. The protein-coding part of the
Fugu MTF-1 gene spans 6.4 kb and consists of 11 exons. Upstream region and first
exon constitute a CpG island. The distance between stop codon and polyadenylation
motifs is >2 kb, suggesting a very long 3' untranslated mRNA region, followed by
another CpG island which may represent the promoter of the next gene downstream.
Part of the MTF-1 genomic structure was also determined in the mouse, and some
striking similarities were found: for example, the upstream adjacent gene in both
species is INPP5P, encoding a phosphatase. The mouse MTF-1 promoter is also
embedded in a CpG island, which however shares no sequence similarity to the one
of Fugu. The Fugu CpG island is shorter than the one of the mouse and has no
elevated [G+C] content; these and other data indicate that CpG islands of fish
may represent a primordial stage of CpG island evolution.
PMID- 10195426
TI - A novel way to induce erythroid progenitor self renewal: cooperation of c-Kit
with the erythropoietin receptor.
AB - Red blood cells are of vital importance for oxygen transport in vertebrates.
Thus, their formation during development and homeostasis requires tight control
of both progenitor proliferation and terminal red cell differentiation. Self
renewal (i.e. long-term proliferation without differentiation) of committed
erythroid progenitors has recently been shown to contribute to this regulation.
Avian erythroid progenitors expressing the EGF receptor/c-ErbB (SCF/TGFalpha
progenitors) can be induced to long-term proliferation by the c-ErbB ligand
transforming growth factor alpha and the steroids estradiol and dexamethasone.
These progenitors have not yet been described in mammals and their factor
requirements are untypical for adult erythroid progenitors. Here we describe a
second, distinct type of erythroid progenitor (EpoR progenitors) which can be
established from freshly isolated bone marrow and is induced to self renew by
ligands relevant for erythropoiesis, i.e. erythropoietin, stem cell factor, the
ligand for c-Kit and the glucocorticoid receptor ligand dexamethasone. Limiting
dilution cloning indicates that these EpoR progenitors are derived from normal
BFU-E/CFU-E. For a detailed study, mEpoR progenitors were generated by retroviral
expression of the murine Epo receptor in bone marrow erythroblasts. These
progenitors carry out the normal erythroid differentiation program in recombinant
differentiation factors only. We show that mEpoR progenitors are more mature than
SCF/TGFalpha progenitors and also do no longer respond to transforming growth
factor alpha and estradiol. In contrast they are now highly sensitive to low
levels of thyroid hormone, facilitating their terminal maturation into
erythrocytes.
PMID- 10195427
TI - An unexpected role for p53 in augmenting SV40 large T antigen-mediated
tumorigenesis.
AB - Simian virus 40 large T antigen transforms cells by sequestration and
inactivation of the tumor suppressor proteins p53, retinoblastoma gene product
(pRb), and the pRb-related proteins p107 and p130. Thus, the absence of
functional p53 is expected to promote T antigen-mediated tumorigenesis. However,
in a transgenic mouse model of T antigen-mediated beta cell carcinogenesis
(Rip1Tag2), tumor volumes are significantly diminished when these mice are
intercrossed with p53-deficient mice. Whereas the incidence of beta tumor cell
apoptosis is unaffected, their proliferation rate is reduced in p53-deficient
beta cell tumors in vivo and in cell lines established from these tumors in
vitro. Biochemical analyses reveal higher levels of T antigen in wild-type tumor
cells as compared to p53-deficient tumor cells. The data indicate that p53
stabilizes SV40 large T antigen, thereby augmenting its oncogenic potential as
manifested by increased proliferation rates in wild-type beta tumor cells as
compared to p53-deficient beta tumor cells.
PMID- 10195428
TI - The Epstein-Barr virus nuclear antigen 2 (EBNA2), a protein required for B
lymphocyte immortalization, induces the synthesis of type I interferon in
Burkitt's lymphoma cell lines.
AB - Epstein-Barr virus nuclear antigen 2 (EBNA2), a protein involved in cell
transformation, interferes with the cellular response to type I interferons (IFN
alpha/beta). We investigated the function of conditionally expressed EBNA2 in the
context of the IFN response in Burkitt's lymphoma cell lines. Expression of EBNA2
led to the transcriptional activation of both endogenous or transfected IFN
stimulated genes (ISGs), genes which contain within their promoters either the
interferon-stimulated response element (ISRE) or the gamma interferon activation
site (GAS). In search of a molecular mechanism for the transcriptional induction
of ISGs, we observed an EBNA2-dependent synthesis of IFN-beta mRNA at low levels
and the secretion of low amounts of IFN. A transfected IFN-beta promoter
responded to EBNA2 activation, and a sequence closely resembling a RBP-Jkappa
binding site was pinpointed as a potential target of EBNA2 activity. EBNA2
dependent transcriptional induction of the IFN-beta promoter occurred in EBV
negative Burkitt's lymphoma cells, indicating that other EBV genes were not
required for the induction of IFN-beta synthesis.
PMID- 10195429
TI - Regulation of human c-Abl tyrosine kinase activity in Xenopus oocytes and
acceleration of progesterone-induced G2/M transition by oncogenic forms.
AB - Deregulated activity of the Abl protein tyrosine kinase is oncogenic in humans
and in animals. The normal cellular form of the enzyme is maintained at a low
state of activity by mechanisms that have not yet been entirely elucidated. In
particular, little is known about the trans-acting cellular factors involved. We
have tested the activity of human c-Abl microinjected into oocytes of Xenopus
laevis. In contrast to versions of Abl capable of transforming mammalian cells,
which were highly active when introduced into oocytes, the activity of wild type
c-Abl was inhibited. Oncogenic forms of Abl efficiently enhanced the ability of
Xenopus oocytes to enter M phase following stimulation by progesterone. Abl
enhanced maturation was normal as judged by accumulation of Mos as well as
activation of MAP kinase and Cdc2/CyclinB (MPF). Concomitant with maturation and
activation of these kinases, Abl became extensively phosphorylated. Altogether,
this suggests that an SH3 domain-dependent Abl regulation mechanism similar to
the one observed in mammalian cells operates in Xenopus oocytes. Maturation
enhancement by microinjection into Xenopus oocytes represents a useful novel
assay for analyzing Abl activity. Moreover, the Xenopus oocyte may be a
convenient source of trans-acting Abl regulators for biochemical studies.
PMID- 10195430
TI - Cmdr1, a chicken P-glycoprotein, confers multidrug resistance and interacts with
estradiol.
AB - We have cloned from a chicken intestinal cDNA library Cmdr1, the first avian P
glycoprotein. Cmdr1 is 67% and 69% identical to proteins encoded by the human
MDR1 and MDR2 genes, respectively. Functional expression of Cmdr1 in both mouse
NIH 3T3 and yeast cells demonstrated that Cmdr1 represents the avian ortholog of
human Mdr1, since it confers resistance to several anticancer drugs and the
fluorescent dye rhodamine 6G. Northern and immunoblot analysis showed that CMDR1
is highly expressed throughout the intestine and in the liver, and to a
considerable extent in kidney, brain, lung, heart, eye and follicles. In situ
hybridization revealed a cell type-specific expression of CMDR1 in the intestinal
epithelium, with high levels in the villi of the small and large intestine as
well as crypt cells. These data suggest that Cmdr1 could play a role in
intestinal detoxification. Most interestingly, immunoblotting showed that Cmdr1
is also expressed in ovarian tissues, particularly in theca cells, the major site
for ovarian estrogen production in birds. Indeed, competition experiments
indicated that Cmdr1 interacts with estradiol, since rhodamine 6G efflux was
efficiently blocked by estradiol in NIH 3T3 cells expressing Cmdr1. Rhodamine
efflux was also blocked by PSC-833, a specific inhibitor of steroid-transporting
P-glycoproteins from mammalian cells. We propose that Cmdr1 in ovarian cells
could be involved in the cell type-specific transport or release of estrogen that
is essential for avian follicular development.
PMID- 10195431
TI - Probing ribosome structure by europium-induced RNA cleavage.
AB - Divalent metal ions are absolutely required for the structure and catalytic
activities of ribosomes. They are partly coordinated to highly structured RNA,
which therefore possesses high-affinity metal ion binding pockets. As metal ion
induced RNA cleavages are useful for characterising metal ion binding sites and
RNA structures, we analysed europium (Eu3+) induced specific cleavages in both
16S and 23S rRNA of E. coli. The cleavage sites were identified by primer
extension and compared to those previously identified for calcium, lead,
magnesium, and manganese ions. Several Eu3+ cleavage sites, mostly those at which
a general metal ion binding site had been already identified, were identical to
previously described divalent metal ions. Overall, the Eu3+ cleavages are most
similar to the Ca2+ cleavage pattern, probably due to a similar ion radius.
Interestingly, several cleavage sites which were specific for Eu3+ were located
in regions implicated in the binding of tRNA and antibiotics. The binding of
erythromycin and chloramphenicol, but not tetracycline and streptomycin,
significantly reduced Eu3+ cleavage efficiencies in the peptidyl transferase
center. The identification of specific Eu3+ binding sites near the active sites
on the ribosome will allow to use the fluorescent properties of europium for
probing the environment of metal ion binding pockets at the ribosome's active
center.
PMID- 10195432
TI - The Oct-1 POU domain directs developmentally regulated nuclear translocation in
Xenopus embryos.
AB - Early embryonic development in Xenopus is characterized by transcriptional
repression which is relieved at the mid-blastula stage. Here we show that most of
the maternally inherited POU domain transcription factor Oct-1 is retained in the
cytoplasm during early development, and that it gradually translocates to the
nucleus around the mid-blastula transition. Overexpressed epitope-tagged Oct-1
exhibits highly similar localization properties compared to endogenous protein.
The amino acid sequence that directs this developmentally regulated nuclear
translocation resides in the POU domain. Our findings may suggest that
cytoplasmic retention of Oct-1 facilitates or contributes to the repression of
Oct-1 target genes before the mid-blastula transition.
PMID- 10195433
TI - Constitutive expression of interleukin-1beta (IL-1beta) in rat oligodendrocytes.
AB - The RT-PCR analysis of RNA from progenitor and differentiated primary rat
oligodendrocytes, and from the oligodendrocyte CG-4 cell line, shows the presence
of the IL-1beta mRNA, the type I IL-1beta receptor and the IL-1 receptor
accessory protein in these cells. In situ hybridization of a rat IL-1beta probe
to primary progenitor and differentiated rat oligodendrocytes results in a
positive signal. The double hybridization of the IL-1beta probe, together with an
oligodendrocyte-specific differentiation marker, to sections of postnatal rat
brain at different stages of differentiation is also positive. The double immuno
labelling technique utilized indicates coincidence of the signals on the brain
slices. The results show that IL-1beta mRNA is constitutively expressed in rat
brain oligodendrocytes from 1 day after birth onward. In agreement with this
observation, CG-4 cells, primary progenitor and differentiated rat
oligodendrocytes are positively stained by antibodies against IL-1beta. Postnatal
brain slices from 1 and 4 day old and adult rats, labelled with a double
immunofluorescence technique, are also stained by antibodies against IL-1beta.
This signal coincides with that of antibodies against oligodendrocyte-specific
surface markers. We conclude that IL-1beta is constitutively expressed in rat
brain progenitor and differentiated oligodendrocytes.
PMID- 10195434
TI - Conformational study of the HIV-1 reverse transcriptase inhibitor 1-[(2
hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT).
AB - The conformations of the HIV-1 reverse transcriptase inhibitor 1-[(2
hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) are calculated by
semiempirical and mainly by ab initio methods in order to estimate the potential
for the rotation around the carbon sulfur single bond. The results are compared
to X-ray structures of HEPT associated to the HIV-1 reverse transcriptase. The
NMR spectra of the compound are calculated to obtain some information about its
structure in solution. The structure of HEPT in the complex is analysed to study
the intermolecular interactions between the inhibitor and the surrounding
protein, which determine the geometry of the inhibition complex.
PMID- 10195435
TI - Transient transfection of mammary epithelial cells with a PEI/DNA/adenovirus
system.
AB - Studies on epithelial cells often require the transient expression of exogenous
proteins in polarized epithelial cells. However, the major limitation of this
approach has been the difficulty of obtaining transient gene expression in
polarized epithelial cell cultures. We report here on the application of a
polyethylenimine (PEI)/DNA/adenovirus system for efficient transient gene
expression in mammary epithelial cells. Based on luciferase assay and FACScan
analysis the PEI/DNA/adenovirus system is shown to be an effective and simple
method for transfecting epithelial cells.
PMID- 10195436
TI - Gaegurin 4, a peptide antibiotic of frog skin, forms voltage-dependent channels
in planar lipid bilayers.
AB - Gaegurin 4 (GGN4) is a cationic peptide of 37 amino acids (MW 3748) isolated from
the skin of Rana rugosa. It has shown a broad spectrum antimicrobial activity in
vitro against Gram-negative and -positive bacteria, fungi and protozoa. To
understand its mechanism of antimicrobial action, we examined the effect of GGN4
on the membrane conductance and the electrical properties of GGN4-induced pores
in planar lipid bilayers under voltage clamp. Natural and synthetic GGN4 (0.01-1
microg/mL) increased the membrane conductance in a concentration-dependent
manner, but GGN4 (1-23), an N-terminal fragment of the peptide with little
antimicrobial activity, failed to increase the conductance. At symmetrical 100 mM
KCI, unitary conductances of about 120 pS were frequently observed. Their current
voltage relations were linear and open state probabilities were close to 1, but
longer closing events were seen more frequently at negative voltages. In
addition, GGN4-induced pores were selective for cation over anion, the
permeability ratio of K+ to Cl- being 6: 1 in neutral and 7: 1 in acidic lipid
bilayers. In conclusion, our results indicate that GGN4 forms voltage-dependent
and cation-selective pores in planar lipid bilayers. The ionophoric property of
GGN4 is likely to contribute to its antimicrobial activity.
PMID- 10195438
TI - A Ca2+ binding cyclic peptide derived from the alpha-subunit of LFA-1: inhibitor
of ICAM-1/LFA-1-mediated T-cell adhesion.
AB - The objective of this work is to study the conformation of cyclic peptide (1),
cyclo (1, 12) Pen1-Gly2-Val3-Asp4-Val5-Asp6-Gln7-+ ++Asp8-Gly9-Glu10-Thr11-Cys12,
in the presence and absence of calcium. Cyclic peptide 1 is derived from the
divalent cation binding sequence of the alpha-subunit of LFA-1. This peptide has
been shown to inhibit ICAM-1-LFA-1 mediated T-cell adhesion. In order to
understand the structural requirements for this biologically active peptide, its
solution structure was studied by nuclear magnetic resonance (NMR), circular
dichroism (CD) and molecular dynamics simulations. This cyclic peptide exhibits
two types of possible conformations in solution. Structure I is a loop-turn-loop
type of structure, which is suitable to bind cations such as EF hand proteins.
Structure II is a more extended structure with beta-hairpin bend at Asp4-Val5
Asp6-Gln7. There is evidence that alterations in the conformation of LFA-1 upon
binding to divalent cations cause LFA-1 to bind to ICAM-1. To understand this
mechanism, the cation-binding properties of the peptide were studied by CD and
NMR. CD studies indicated that the peptide binds to calcium and forms a 1 : 1
(peptide: calcium) complex at low calcium concentrations and multiple types of
complexes at higher cation concentrations. NMR studies indicated that the
conformation of the peptide is not significantly altered upon binding to calcium.
The peptide can inhibit T-cell adhesion by directly binding to ICAM-1 or by
disrupting the interaction of the alpha and beta-subunits of LFA-1 protein. This
study will help us to understand the mechanism(s) of action of this peptide and
will improve our ability to design a better inhibitor of T-cell adhesion.
PMID- 10195437
TI - The influence of Lys68 in decepeptide agonists of C5a on C5a receptor binding,
activation and selectivity.
AB - The potent, conformationally biased C5a agonist peptide YSFKPMPLaR (C5a65-74,
Y65, F67, P69, P71, D-Ala73) was used as a template to gain insight into the
nature and importance of lysine at position 68 in the peptide-receptor
interaction. A panel of YSFKPMPLaR analogs with systematic substitutions for
Lys68 was evaluated for C5a receptor (C5aR) binding affinity and activation in
two well-characterized assay systems: human polymorphonuclear leukocytes (PMNs)
and human fetal artery. In addition, we determined the activity of these new
analogs in transfected rat basophilic leukemia (RBL) cells in which the Glu at
position 199 of the C5aR (wtGlu199) was replaced by a Gln (C5aR-Gln199) or a Lys
(C5aR-Lys199). Our results indicated that Lys68 in YSFKPMPLaR plays an important
role in binding the C5aR expressed on PMNs and RBL cells. Furthermore, the data
indicated that Lys68 interacted with Glu199 of the C5aR in PMNs and RBL cells. In
human fetal artery, however, Lys68 substitutions had little or no effect on
activity, which suggested that the receptor conformation may be different in this
tissue. Thus, the interaction between Lys68 of the decapeptide agonist and Glu199
of the C5aR may be cell type-specific and may form the molecular basis for tissue
specific responses to C5a agonists.
PMID- 10195439
TI - Conformational study of Ac-Xaa-Pro-NHMe dipeptides: proline puckering and
trans/cis imide bond.
AB - The conformational study on 20 Ac-Xaa-Pro-NHMe dipeptides has been carried out
using an empirical potential function ECEPP/3 in order to investigate the factors
responsible for the preference of proline puckering of the peptides with the
trans or cis imide bond preceding the proline. The general conformational
preference for down- and up-puckered dipeptides is calculated as trans-down >
trans-up > cis-down > cis-up, which is reasonably in accord with that estimated
by analyzing X-ray structures of proteins and the result for the single proline
residue. The overestimated occurrence of trans-down conformations of proline
seems to be caused by excluding long-range interactions that short dipeptides
cannot have. The average computed occurrence of dipeptides with cis imide bonds
is about 3%, somewhat lower than the value calculated for Ac-Pro-NHMe, which is
close to experimental estimates obtained from X-ray structures of proteins. In
particular, the interaction of the aromatic side chain of Xaa residue with the
proline ring appears not to be strong enough to stabilize the stacked
conformations of small dipeptides with cis imide bonds. The propensity to adopt
trans or cis imide bond and to form secondary structures of Xaa-Pro sequences is
discussed and compared with results obtained from X-ray structures of proteins.
PMID- 10195440
TI - Structure-activity relationship study: short antimicrobial peptides.
AB - Many short antimicrobial peptides (< 18mer) have been identified for the
development of therapeutic agents. However, Structure-activity relationship (SAR)
studies about short antimicrobial peptides have not been extensively performed.
To investigate the relationship between activity and structural parameters such
as an alpha-helical structure, a net positive charge and a hydrophobicity, we
synthesized and characterized diastereomers, scramble peptides and substituted
peptides of the short antimicrobial peptide identified by combinatorial
libraries. Circular dichroism (CD) spectra and in vitro activity indicated that
an alpha-helical structure correlated with the antimicrobial activity and a beta
sheet structure also satisfied a structural requirement for antimicrobial
activity. Most peptides consisting of L-amino acids lost antifungal activity in
the presence of heat-inactivated serum, while active diastereomers and a scramble
peptide with the beta-sheet structure retained antifungal activity in the same
condition.
PMID- 10195441
TI - Addition and omission analogs of the 13-residue antibacterial and hemolytic
peptide PKLLKTFLSKWIG: structural preferences, model membrane binding and
biological activities.
AB - The consequences of selective addition or deletion of polar amino acids in a 13
residue antibacterial peptide PKLLKTFLSKWIG on structure, membrane binding and
biological activities have been investigated. The variants generated are (a) S
and T residues replaced by K, (b) S and T residues deleted individually and
together, (c) introduction of two additional K and (d) deletion of L and L with
T. In the aqueous environment all the peptides were unordered. In
trifluoroethanol, the spectra of peptides belonging to groups (a-c) suggest
distorted helical conformation. Peptides in group (d) appear to adopt beta-sheet
conformation. The peptides bind to zwitterionic and negatively charged lipid
vesicles, although to different extents. With the exception of peptides in group
(d), all the other peptides exhibited comparable antibacterial activity against
Escherichia coli and Staphylococcus aureus. However, the changes made in the
peptides in groups (a-c) resulted in reduction of hemolytic activity compared to
the parent peptide. Extent of binding to lipid vesicles composed of
phosphatidylcholine and cholesterol appears to correlate with hemolytic activity.
It appears that polar and charged residues play a major role in modulating the
biological activities of the 13-residue peptide PKLLKTFLSKWIG. The 11-residue
peptide-like PKLLKFLKWIG has selective antibacterial activity. Thus, by judicious
engineering it should be possible to generate short peptides with selective
antibacterial activity.
PMID- 10195442
TI - A comparative study of cyclization strategies applied to the synthesis of head-to
tail cyclic analogs of a viral epitope.
AB - A family of head-to-tail cyclic peptide models of the antigenic site A (G-H loop
of viral protein 1) of foot-and-mouth disease virus has been designed on the
basis of the three-dimensional structure adopted by the linear peptide
YTASARGDLAHLTTT upon binding to neutralizing monoclonal antibodies. Three
different methods of cyclization have been examined to access the peptides.
Solution cyclization of a minimally protected linear precursor provided the
expected products but required several purification steps that lowered the yields
to approximately 10%. The two other approaches relied on side-chain anchoring of
the peptide through the Asp residue and cyclization on the solid phase. A
synthetic scheme combining Fmoc, tBu and OAI protections was practicable but
inefficient when scaled-up. The combination of Boc, Bzl and OFm protections was
more promising, but suffered from high epimerization during the initial
esterification of Boc-Asp-OFm to benzyl alcohol-type resins. This problem was
solved by performing the esterification via the cesium salt of Boc-Asp-OFm. With
this improvement, the Boc/Bzl/OFm has become the method of choice for the
preparation of cyclic head-to-tail peptides in satisfactory yields and with
minimal purification.
PMID- 10195443
TI - A cyclic peptide analogue of the loop III region of platelet-derived growth
factor-BB is a synthetic antigen for the native protein.
AB - We report the synthesis and characterization of a cyclic peptide analogue of the
loop III region of platelet-derived growth factor (PDGF) B-chain sequence,
cyclo(73Arg-Lys-Ile-Glu-Ile-Val-Arg-Lys-Lys81-Cys), incorporating a C-terminus
cysteine residue for the conjugation to a carrier protein. The synthesis involved
solid-phase chemistry, utilizing Fmoc-tBu chemistry and acid labile side-chain
protecting groups, followed by 'head-to-tail' cyclization using the allyl
protected glutamic acid anchored on its side chain to the solid support with
HATU/HOAt as the coupling agent. Conformational differences between the cyclic
and its linear counterpart PDGF peptides were determined by circular dichroism
measurements in aqueous media. High titre antisera were raised to both cyclic and
linear peptide immunogens. Antisera raised to the cyclic peptide cross-reacted
with PDGF-BB in both Western blot and ELISA, whereas antisera raised to the
linear peptide had no reactivity with PDGF-BB. The cyclic peptide (conformational
design analogue) produces an immunogen which is able to antigenically mimic the
secondary structure of loop III of PDGF-BB and forms a basis from which further
small molecular mimetics of PDGF may be designed for use as both immunogens and
also potential agonists/antagonists of PDGF. Similarly constructed immunogens may
also be useful in the design of vaccines which direct responses to loop regions
in other target proteins.
PMID- 10195444
TI - Conformational changes of polyomavirus major capsid protein VP1 in sodium dodecyl
sulfate solution.
AB - Conformations of polyomavirus (Py) major capsid protein VP1 were analyzed by
circular dichroism (CD) and fluorescence spectroscopy in the presence of sodium
dodecyl sulfate (SDS). Binding of PyVP1 to SDS induced marked conformational
changes of PyVP1, which were reflected on the CD and fluorescence spectra. Abrupt
changes in both optical properties occurred within the narrow ranges of SDS
concentrations with the transition midpoints closely related to SDS micelle
formation. Analysis of circular dichroism spectra showed that the contents of
alpha-helices, beta-sheets, beta-turns and random coils in PyVP1 varied upon
addition of SDS, demonstrating the exquisite sensitivity of the conformations of
the protein to the environment. The interactions of PyVP1 with SDS were shown to
be dependent on the ionic strength of the protein solution, suggesting that both
hydrophobic and electrostatic forces contribute to the PyVP1-SDS complex
formation. The SDS-induced conformational changes of PyVP1 appeared to be a two
stage process.
PMID- 10195445
TI - Structure-antibacterial, antitumor and hemolytic activity relationships of
cecropin A-magainin 2 and cecropin A-melittin hybrid peptides.
AB - In order to elucidate the structure-antibiotic activity relationship of cecropin
A-magainin 2 and cecropin A-melittin hybrid peptides, several truncated peptides
and the analogues with amino acid substitutions were synthesized and their
antibacterial, antitumor and hemolytic activities of were examined. Cecropin A
magainin 2 hybrid analog, L16-CA(1-8)-MA(1-12) (termed as L-CA-MA in this study:
KWKLFKKIGIGKFLHLAKKF-NH2), is known to have potent antibacterial and antitumor
activity with less hemolytic activity. We found that the C-terminal region of L
CA-MA is more involved in the alpha-helical structure on cell membrane-like
environment than N-terminal one by circular dichroism analysis. Deletion of the
Gly-Ile-Gly sequence, the central hinge region of L-CA-MA, produced a
considerable reduction in antitumor and hemolytic activity rather than an
antibacterial one. The insertion of Pro, Gly-Ile or Gly-Pro in this hinge region
of L-CA-MA caused retention of both antibacterial and antitumor activity while
causing a significant decrease in hemolytic activity. However, the substitution
with Gly-Pro-Gly instead of the Gly-Ile-Gly in CA(1-8)-MA(1-12), CA(1-8)-ME(1
12), CA(1-13)-MA(1-13) and CA(1-13)-ME(1-13) hybrids resulted in a drastic
decrease in antibacterial, antitumor and hemolytic activity. The increase of
hydrophobicity at position 16 in CA(1-8)-MA(1-12) by substituting Trp or Phe
induced a significant increase in hemolytic activity without a considerable
change in either antibacterial or antitumor activity. Therefore, these results
suggested that the appropriate flexibility in the hinge region of CA-MA and CA-ME
hybrid peptides and the appropriate hydrophobicity at position 16 in the
hydrophobic region of CA (1-8)-MA(1-12) are important in potent antibacterial and
antitumor activity with no hemolytic effect.
PMID- 10195446
TI - Removal of iodine by solid phase adsorption to charcoal following iodine
oxidation of acetamidomethyl-protected peptide precursors to their disulfide
bonded products: oxytocin and a Pre-S1 peptide of hepatitis B virus illustrate
the method.
AB - Chemical quenching, gel filtration or liquid phase extraction procedures are
currently in vogue for taking iodine off from the reaction mixtures in which it
is used to cause the formation of disulfide bonds in acetamidomethyl or trityl
protected peptides. It has been found that charcoal effectively, selectively and
rapidly removes iodine by solid phase extraction from reaction mixtures in which
it is used to convert the acetamidomethyl protected precursors of oxytocin or a
peptide from the Pre-S1 region of hepatitis B virus into their intramolecularly
disulfide-bonded products. The advantages of this new method, namely simplicity,
rapidity, quantitative yields, freedom from side reactions, linear scalability,
cost effectiveness and adsorption of iodine on to solid charcoal are discussed.
PMID- 10195447
TI - Evidence for helicity in insect diuretic peptide hormones: computational
analysis, spectroscopic studies, and biological assays.
AB - The conformation of four insect diuretic hormones has been analyzed
computationally using secondary structure prediction routines and comparison with
structures in the Brookhaven Protein Databank. Based on this analysis, a common
seven-residue peptide fragment (DVLRQRL) had a high probability of forming an
alpha-helix. Circular dichroism (CD) studies found that addition of
trifluoroethanol (TFE) to an aqueous solution of the seven-residue fragment
induces a change from random coil to helix. Subsequent NMR studies in water-TFE
(1:1) produced nOe values and 3JalphaNH coupling constants confirming a helical
conformation: 3JalphaNH coupling constants for the first five residues (D1 to Q5)
were all < or = 6.0 Hz and two medium-range nOe values (dalphaN (i,i+3)) were
observed between V2 and Q5, and R4 and L7. The longer fragments PLDVLRQRL in
water-TFE and Lom-DH 1-26 in water alone, both containing the DVLRQRL sequence of
the locust (Locusta migratoria) diuretic hormone, maintained the helicity as
determined by CD analysis. However, the remaining 20 residues of the locust
diuretic hormone did not maintain the same amount of helicity in water and all of
the truncated fragments were not biologically active.
PMID- 10195449
TI - Biological actions of the epidermal growth factors-like domain peptides of mouse
schwannoma-derived growth factor and human amphiregulin.
AB - Several members of the epidermal growth factor (EGF) family of growth factors
that contain EGF-like units at their carboxy portion have been isolated and
characterized. Schwannoma-derived growth factor (SDGF) and amphiregulin (AR) are
members of this family. SDGF has high sequence homology to AR, and is known to be
not only a potent mitogen for astrocytes and fibroblasts but also a neurotrophic
factor. We previously confirmed that the synthetic EGF-like peptides SDGF(38-80)
and AR(44-84), corresponding to the EGF-like domain of mouse SDGF and human AR,
respectively, formed similar disulfide bond patterns to that of EGF. In the
present study, we further investigated the biological actions of these two EGF
like peptides on several cultured cell lines. We found that SDGF(38-80) and AR(44
84) have weak mitogenic activity in NIH/3T3 cells and weak binding affinity to
the EGF receptor on the surface of A431 cells compared with EGF. However, SDGF(38
80) and EGF induced short neurite outgrowth in PC12 h cells, a subclone of PC12
cells, at 100 nM. In addition, a significant increase in acetylcholinesterase
(AChE) activity induced by SDGF(38-80) was observed at a concentration similar
range to that of EGF, which is known as a differentiation marker of these cells.
The effect of AR(44-84) in PC12 h cells was weaker than those of SDGF(38-80) and
EGF, but the AChE activity was significantly increased by the addition of 100 nM
AR(44-84), which did not stimulate NIH/3T3 cell growth. These results also
suggest that SDGF(38-80) and AR(44-84) may be effective for neuronal
differentiation rather than proliferation.
PMID- 10195448
TI - Chromogenic and fluorogenic glycosylated and acetylglycosylated peptides as
substrates for serine, thiol and aspartyl proteases.
AB - We synthesized short chromogenic peptidyl-Arg-p-nitroanilides containing either
(Galbeta)Ser or (Glcalpha,beta)Tyr at P2 or P3 sites as well as O-acetylated
sugar moieties and studied their hydrolysis by bovine trypsin, papain, human
tissue kallikrein and rat tonin. For comparison, the susceptibility to these
enzymes of Acetyl-X-Arg-pNa and Acetyl-X-Phe-Arg-pNa series, in which X was Ala,
Phe, Gln and Asn were examined. We also synthesized internally quenched
fluorescent peptides with the amino acid sequence Phe8-His-Leu-Val-Ile-His-Asn14
of human angiotensinogen, in which [GlcNAcbeta]Asn was introduced before Phe8
and/or after His13 and ortho-aminobenzoic acid (Abz) and N-[2-, 4-dinitrophenyl]
ethylenediamine (EDDnp) were attached at N- and C-terminal ends as a
donor/receptor fluorescent pair. These peptides were examined as substrates for
human renin, human cathepsin D and porcine pepsin. The chromogenic substrates
with hydrophilic sugar moiety increased their susceptibility to trypsin, tissue
kallikrein and rat tonin. For papain, the effect of sugar depends on its position
in the substrate, namely, at P3 it is unfavorable, in contrast to the P2 position
that resulted in increasing affinity, as demonstrated by the higher inhibitory
activity of Ac-(Gal3)Ser-Arg-pNa in comparison to Ac-Ser-Arg-pNa, and by the
hydrolysis of Ac-(Glcalpha,beta)Tyr-Arg-pNa. On the other hand, the acetylation
of sugar hydroxyl groups improved hydrolysis of the susceptible peptides to all
enzymes, except tonin. The P'4 glycosylated peptide [Abz-F-H-L-V-I-H
(GIcNAcbeta)N-E-EDDnp], that corresponds to one of the natural glycosylation
sites of angiotensinogen, was shown to be the only glycosylated substrate
susceptible to human renin, and was hydrolysed with lower K(m) and higher k(cat)
values than the same peptide without the sugar moiety. Human cathepsin D and
porcine pepsin are more tolerant to substrate glycosylation, hydrolysing both the
P'4 and P4 glycosylated substrates.
PMID- 10195450
TI - Synthesis and characterization of a series of novel glutamic gamma-15N-anilide
dipeptides.
AB - The preparation of a series of novel Cbz-Gln-Gly dipeptide derivatives is
reported, wherein the gamma-carboxamide groups of the glutamine side chains have
been modified to gamma-15N-anilides which are substituted in the para position
with -NO2, -Cl, -H, -CH3, -OCH3, and -N(CH3)2. Characterization of the free
anilines (p(kappa)a values and 15N NMR chemical shifts) and corresponding gamma
anilides (15N NMR chemical shifts and FTIR wavenumbers) is also reported.
Correlation of these physicochemical data to Hammett substituent parameters
((sigma)para) is discussed. These novel dipeptide derivatives should prove to be
generally useful for structure-function enzymology studies of gamma-glutamyl
transferring enzymes.
PMID- 10195451
TI - Synthesis and binding potencies of cyclic hexapeptide analogs of somatostatin
incorporating acidic and basic peptoid residues.
AB - The synthesis, binding affinity, and structure-activity relationships of
compounds related to the cyclic hexapeptide, c[Pro6-Phe7-D-Trp8-Lys9-Thr10
Phe11], L-363,301 (the numbering in the sequence refers to the position of the
residue in native somatostatin) is reported. The Pro residue in this compound is
replaced with the peptoid residues Nasp [N-(2-carboxyethyl) glycine], Ndab [N-(2
aminoethyl) glycine] and Nlys [N-(4-aminobutyl) glycine]. This series of
compounds enables us to draw conclusions about the influence of positively or
negatively charged residues in the bridging region on the binding affinity
towards the isolated human somatostatin receptors. A loss of binding to the
recombinant human somatostatin (hsst) receptors in the Nasp analog compared with
L-363,301 and compared with the Ndab and Nlys analogs clearly demonstrates that
the presence of an acidic residue in the bridging region is unfavorable for
binding to the hsst receptors. Comparison between the Ndab analog and the Nlys
analog suggests that the presence of a basic residue in the bridging region might
be advantageous for binding to the hsst5 receptor provided that the residue
bearing the basic group extends far enough to allow for interaction with the
receptor, while the length of the basic peptoid residue does not influence
binding to the hsst2 receptor. These results are useful for the design of hsst5
selective somatostatin analogs.
PMID- 10195452
TI - Conformational analyses by 1H NMR and computer simulations of cyclic hexapeptides
related to somatostatin containing acidic and basic peptoid residues.
AB - We report the conformational analysis by 1H NMR in DMSO and computer simulations
involving distance geometry and molecular dynamics simulations at 300K of peptoid
analogs of the cyclic hexapeptide c-[Phe11-Pro6-Phe7-D-Trp8-Lys9-Thr10]. The
analogs c-[Phe11-Nasp6-Phe7-D-Trp8-Lys9-Thr10](1), c-[Phe11-Ndab6Phe7-D-Trp8-Lys9
Thr10] (2) and c-[Phen11-Nlys6-Phe7-D-Trp8-Lys9-Thr10](3) where Nasp denotes N-(2
carboxyethyl) glycine, Ndab N-(2-aminoethyl) glycine and Nlys N-(4-aminobutyl)
glycine are subject to conformational studies. The results of free and restrained
molecular dynamics simulations at 300K are reported and give insight into the
conformational behaviour of these analogs. The compounds show two sets of nuclear
magnetic resonance signals corresponding to the cis and trans orientations of the
peptide bond between residues 11 and 6. The backbone conformation of the cis
isomers that we believe are the bioactive isomers of the three compounds are very
similar to each other while there are larger variations amongst the trans
isomers. The binding data to the isolated receptors show that the introduction of
the Nlys residue in analog 3 leads to an enhancement of binding potency to the
hsst5 receptor compared with analog 2 while maintaining identical binding potency
to the hsst2 receptor. The Nasp6 analog 1 binds weakly to the hsst2 and is
essentially inactive towards the other receptors. Comparison of the conformations
and binding activities of these three analogs indicates that the Nlys residue
extends sufficiently far to allow binding to a negatively charged binding domain
on the hsst5 receptor. According to this model, the Ndab analog 2 cannot extend
far enough to allow for binding to the receptor pocket. The loss of activity
observed for the Nasp6 compound 1 indicates that the presence of a negatively
charged residue in position 6 is unfavorable for binding to the hsst receptors.
PMID- 10195453
TI - Study on the synthesis and characterization of peptides containing phosphorylated
tyrosine.
AB - Phosphorylation and dephosphorylation are key events in receptor-mediated and
post-receptor-mediated signal transduction. Synthetic phosphopeptides have been
shown to have dramatic agonist or antagonist effects in several of these
signaling pathways. For its 1997 study, the Association of Biomolecular Resource
Facilities (ABRF) Peptide Synthesis Research Group assessed the ability of member
laboratories to synthesize phosphotyrosine peptides. Participating laboratories
were requested to synthesize and submit the following crude peptide, H-Glu-Asp
Tyr-Glu-Tyr(PO3H2)-Thr-Ala-Arg-Phe-NH2, for evaluation by amino acid analysis,
sequence analysis, RP-HPLC, MALDI-TOF and ESI mass spectrometry. Prior to
analysis of submitted peptides from ABRF members, the Peptide Synthesis Research
Group synthesized and characterized the nonphosphorylated form of the peptide,
the doubly phosphorylated form and the peptides singly phosphorylated on either
the first or the second tyrosine. These peptide standards were separated easily
by HPLC and capillary electrophoresis and the phosphotyrosine was detected
readily by Edman degradation sequence analysis. No differences were seen by amino
acid analysis and the expected masses were observed by mass spectrometry. The two
singly phosphorylated peptides were easily distinguished by MALDI-PSD. Analysis
of the peptides submitted from member facilities revealed that all but four of
the 33 samples contained the correct product as determined by HPLC and mass
spectrometry. HPLC analysis indicated that 20 of the 33 submitted samples
contained greater than 75% correct product, five contained less than 50% correct
product and four did not contain any correct product. By ESI/MS, an additional
singly charged ion at m/z 535.5 was detected in five of the 33 submitted samples;
this ion was subsequently shown to represent Ac-TARF-NH2. No correlation was
found to exist between coupling time and percentage correct product; however, a
correlation may exist between a greater percentage of correct product and the use
of non-protected phosphotyrosine.
PMID- 10195454
TI - Dipeptide derivative synthesis catalyzed by Pseudomonas aeruginosa elastase.
AB - Pseudomonas aeruginosa elastase was used to synthesize various N-protected
dipeptide amides. The identity of the products was confirmed by FAB(+)-MS. After
recrystallization, the yield of their synthesis was calculated, their purity was
checked by RP-HPLC and their melting point was measured. With regard to the
hydrolysis, it is well-established that the enzyme prefers hydrophobic amino
acids in P'1 position and it has a wide specificity for the P1 position. This
specificity was demonstrated to be quite unchanged when comparing the initial
rates of peptide bond formation between different carboxyl donors (Z-aa) and
nucleophiles (aa-NH2). The elastase, but not the thermolysin, was notably able to
incorporate tyrosine and tryptophan in P'1 position. Furthermore, synthesis
initial rates were at least 100 times faster with the elastase. To overcome the
problematic condensation of some amino acids during chemical peptide synthesis,
it has been previously suggested that enzymatic steps can combine with a chemical
strategy. We demonstrated that the elastase readily synthesizes dipeptide
derivatives containing various usual N-protecting groups. It was especially able
to condense phenylalaninamide to Fmoc- and Boc-alanine. Increasing interest in
peptides containing unnatural amino acids led us to try the elastase-catalyzed
synthesis of Z-dipeptide amides including those amino acids in the P1 position. A
synthesis was demonstrated with alphaAbu, Nle, Nva and Phg.
PMID- 10195455
TI - Enhanced cleavage of diaminopimelate-containing isopeptides by leucine
aminopeptidase and matrix metalloproteinases in tumors: application to
bioadhesive peptides.
AB - We prepared (2S,6S)-Z-Dpm(Z)(OMe) (4) by protease-mediated hydrolysis of
(R,R/S,S)-Z-Dpm(Z)(OMe)-OMe (3), converted it to (2S,6S)-Dpm(Z)(OMe) (6) via PCI5
to an NCA intermediate and hydrolysis, protected the amino group with Boc to give
(2S,6S)-Boc-Dpm(Z)(OMe) (7), which upon ammonolysis of the Me ester afforded
(2S,6S)-Boc-Dpm(Z)(NH2) (8). Hydrogenolysis of 8 and protection with Fmoc gave
(2S,6S)-Boc-Dpm(Fmoc)(NH2)(10). Using 10 and SPPS, we prepared three Dpm
containing peptides and their corresponding Lys peptides. Enzymatic studies with
mLAP and cLAP showed that the Leu moiety in Ac-Gly-(2S,6S)-Dpm(Leu)(NH2)-Ala (14)
was hydrolyzed 68-fold and >1000-fold more rapidly, respectively, than that in Ac
Gly-Lys(Leu)-Ala (12). The enhanced rate of Leu formation from 14 compared to 12
was also observed with homogenates of mouse C3 sarcomas. This homogenate also
hydrolyzed Ac-Gly-(2S,6S)-Dpm(Ac-Gly-Pro-Gln-Gly-Leu)(NH2)-Ala (16) to Ac-Gly
(2S,6S)-Dpm(NH2)-Ala (13), Leu and Ac-Gly-Pro-Gln-Gly (17). This implies the side
chain is cleaved first by endopeptidases, such as matrix metalloproteinases
(MMPs), and then the remaining Leu is cleaved by LAP-like exopeptidases. The rate
of liberation of 17 from 16 and the corresponding Lys isopeptide, Ac-Gly-Lys(Ac
Gly-Pro-Gln-Gly-Leu)-Ala (15), was not significantly different. The rate of
formation of 13 was faster from 16 than Ac-Gly-Lys-Ala (11) was from 15. Thus,
the entire isopeptide side chain can be removed by the cooperative action of LAP
like and MMP-like peptidases present in tumor tissue, which occurs faster in the
Dpm peptide 16 than in the Lys peptide 15. The rate of formation of 13 from 16 by
lung, liver, and intestine homogenates (from the same C3 tumor-bearing mice) was
comparable to or higher than from the tumor homogenates, but the rate by blood
was only 4% the value of the tumor homogenates. Analogs of a bioadhesive fragment
from the laminin alpha1 chain were prepared by replacing the essential Lys with
Dpm(NH2) (20) and Dpm(Leu)(NH2) (21). Both Dpm-containing peptides were active,
although considerably weaker than the corresponding Lys peptides 18 and 19, in a
cell attachment assay with human fibrosarcoma HT-1080 cells.
PMID- 10195456
TI - Molecular dynamics study of disulfide bond influence on properties of an RGD
peptide.
AB - Three 1 ns length molecular dynamics simulations of an RGD peptide (Ac-Pen-Arg
Gly-Asp-Cys-NH2, with Pen denoting penicillamine) have been performed in aqueous
solution, one for the disulfide bridged, and two for the unbridged form. The
trajectories were analyzed to identify conformations explored by the two forms
and to calculate several properties: NMR vicinal coupling constants, order
parameters, dipole moments and diffusion coefficients, in an effort to describe
the physical role of the disulfide bond. The cyclic peptide was able to explore
several distinct backbone conformations centered around a turn-extended-turn
structure. However, its flexibility was limited and it appeared to be 'locked in'
into a a family of structures characterized by a high dipole moment and a well
defined conformation of the pharmacophore, which has been previously identified
as biologically active. Excellent agreement between the simulated and observed
NMR vicinal coupling constants indicates that realistic structures were sampled
in the cyclic peptide simulation. The linear form of the peptide was much more
flexible than the cyclic one. In the two independent 1 ns simulations of the
linear form the explored conformations could be roughly grouped into two classes,
of cyclic-like and extended type. Within each simulation the peptide switched
between the two classes of structures several times. Exact matches between
conformations in the two linear peptide simulations were not found; several
conformational regions with backbone rms deviations below 1A were identified,
suggesting that representative structures of the linear form have also been
identified. In the linear peptide simulations the RGD pharmacophore is able to
adopt a wide range of conformations, including the one preferred by the cyclic
form. The lower biological activity of the linear peptide compared to the cyclic
one may be correlated with the lower population of this structure in the absence
of the disulfide bond.
PMID- 10195457
TI - Synthesis and characterization of multiply-tyrosinated, multiply-iodinated
somatostatin analogs.
AB - Radio-labeled somatostatin analogs have recently gained popularity as agents
useful in intraoperative tumor localization, external scintigraphy and in situ
radiotherapy. We have synthesized and characterized a series of novel N
terminally extended multiply-tyrosinated somatostatin analogs that possess high
binding affinity for somatostatin receptors, exhibit biological activity
comparable to the native peptide and retain these characteristics after
iodination. These analogs can be radio-iodinated to high specific activities.
Following radioiodination, these analogs exhibit minimal radiolysis and may be
clinically useful for tumor localization, scanning and therapy.
PMID- 10195458
TI - Conformational analysis of biologically active truncated linear analogs of
endothelin-1 using NMR and molecular modeling.
AB - Some linear truncated analogs of endothelin-1 display potent agonistic activity
at the ET(B) receptor, especially when the side chain of Trp21 is N-formylated.
Then, the three-dimensional arrangements of six structurally reduced linear
analogs, three formylated and three nonformylated, have been investigated by high
resolution NMR spectroscopy and molecular modeling, in order to pinpoint the
conformational features related to the biological activity. Two-dimensional
double-quantum-filtered correlation spectroscopy (DQFCOSY), total correlation
spectroscopy (TOCSY) and nuclear Overhauser enhancement spectroscopy (NOESY) were
recorded and analyzed for each molecule. Interspatial distance constraints were
derived from the intensity of the NOESY connectivities. The formation of hydrogen
bonding was monitored from the temperature dependence of the NH chemical shifts.
Molecular models calculated by means of distance geometry, simulated annealing
and energy minimization, using the NMR constraints, strongly suggested a global
elongated structure for the formylated analogs exhibiting biological activity,
and a folded arrangement for the unformylated derivatives. Homology comparisons
allowed the identification of a beta-turn-like folding of the C-terminal segment
Asp18-Trp21 as a probable key-factor for activity.
PMID- 10195459
TI - Secretion of IFN-gamma by bovine peripheral blood mononuclear cells stimulated
with Mycobacterium bovis protein fractions obtained by isoelectric-focusing.
AB - Due to the complexity and variety of biological effects found in Mycobacterium
bovis (M. bovis) proteins analyzed solely on a molecular weight (MW) basis, we
approached the purification of M. bovis proteins through their isoelectric point
(pI). Twenty M. bovis culture filtrate protein extract (CFPE) isoelectric focused
(IEF) protein fractions, confined between pI3 and 10, were isolated. The MW of
the major proteins isolated in the various fractions correlated with protein
already reported 14-, 18-, 20-, 25-, 31-, 38-, 45-, 64-, 67- and 70 kDa by SDS
PAGE. Since several different pI fractions showed proteins of the same MW we
tested the ability of all IEF fractions to stimulate interferon-gamma (IFN-gamma)
production by peripheral blood mononuclear cells (PBMC) isolated from cattle with
well defined M. bovis tuberculosis (TB) infection. In animals with few lesions
IFN-gamma inductive IEF fractions were in the acid range. As the number of
lesions increased, neutral fractions were also inductive. Some fractions with
relatively few proteins induced as much IFN-gamma production as others with
abundant proteins. None of the 20 IEF fractions enhanced IFN-gamma production by
anergic cells. We conclude that IFN-gamma production in diseased animals is
induced mainly by acidic mycobacterial proteins and that the response towards
these proteins is enhanced as the disease progresses, what coincides with higher
PPD reactivity. However, the IFN-gamma production in anergic status was severely
affected. We found that this cytokine production is spontaneous and antigen
independent.
PMID- 10195460
TI - Phenotypic comparison of ileal intraepithelial lymphocyte populations of suckling
and weaned calves.
AB - Ileal intraepithelial lymphocyte (IEL) suspensions from suckling calves (1-3
weeks old) and weaned calves (3-6 months old) were phenotyped to determine
whether there were differences in the lymphocyte populations consistent with
postnatal maturation of the mucosal immune system. Flow cytometric comparisons of
IEL from the two age groups revealed the presence of significantly larger
proportions of CD4+ T lymphocytes and CD8+ T cells in the weaned animals. In
contrast, there was a significantly larger proportion of B-B2+ IEL in the
suckling calves. Freshly isolated IEL from both groups of calves expressed mRNA
for TNF-alpha and IFN-gamma, but not IL-4 or IL-10. The B-B2+ IEL population was
more closely examined by flow cytometry. These cells co-expressed IgM and CD21.
However, they did not express IgA, IgG1, nor any of several additional leukocyte
differentiation molecules. Immunohistochemical data confirmed the presence of
IgM+ lymphocytes, and the paucity of IgA+ and IgG1+ lymphocytes in suckling calf
ileum. However, substantial numbers of IgA+ and IgG1+ cells were observed in
weaned calf ileum. Together, the data are consistent with ongoing postnatal
maturation of the gut mucosal immune system.
PMID- 10195461
TI - Effects of cytokines from thymocytes and thymic stromal cells on chicken
intrathymic T cell development.
AB - We have studied the ability of thymic stromal cells (TSC) and thymocytes to
produce cytokines and the involvement of cytokines in intrathymic T cell
development. When thymocytes were co-cultured with thymic stromal cells in
absence of direct contact and mitogenic stimulation, induction of thymocyte
proliferation was observed. Supernatants of cultured stromal cells (TSC-CS)
promoted a high proliferative response on CD3- thymocytes but had little effect
on CD3+ thymocytes. These results indicate that stromal cells have produced a
cytokine which can induce immature thymocyte proliferation. Moreover, stromal
cells express the MRNA for stem cell factor (SCF) and c-kit (the receptor for
SCF) was detected on CD3- thymocytes but not on CD3+ thymocytes. Since SCF can
enhance the proliferation of immature thymocytes in synergy with IL-7 in mammals,
there is a possibility that chicken stromal cells may produce a IL-7-like factor.
Thymocytes have clearly expressed interferon (IFN)-gamma. In contrast, thymic
stromal cells showed no detectable expression of IFN-gamma. CD3+ thymocytes
express IFN-gamma MRNA more strongly than CD3 thymocytes, suggesting that IFN
gamma from thymocytes may operate on stromal cells and then may indirectly induce
clonal elimination of CD3+ cells on stromal cells. The expression of these
cytokines and receptors by thymic stromal cells and thymocyte subpopulations
suggests that these cytokines participate in paracrine interactions between these
cell populations during thymocyte differentiation.
PMID- 10195462
TI - Streptococcus equi but not Streptococcus zooepidemicus produces potent mitogenic
responses from equine peripheral blood mononuclear cells.
AB - Streptococcus equi causes equine strangles. The acute disease has many of the
hallmarks of an acute response including high fever, elevated plasma fibrinogen
and neutrophilia, affects known to be mediated by proinflammatory cytokines. The
objective of this study was to screen-culture supernatants from equine clinical
isolates of S. equi and S. zooepidemicus for stimulation of mitogenic responses
by horse peripheral blood mononuclear cells. Mitogenicity comparable to that of
concanavalin A was detected in culture supernatants of S. equi strains but not in
those of S. zooepidemicus. Mitogenicity was neutralised by Proteinase K and a
post-strangles convalescent serum, and evidence for the presence of both thermo
resistant and thermo-labile mitogenic factors was obtained. Release of
proteinaceous immunogenic mitogens in combination with the antiphagocytic protein
SeM unique to S. equi may therefore contribute to some of the severe clinical
manifestations of acute strangles in the horse.
PMID- 10195463
TI - Secretion of 92 kDa gelatinase (MMP-9) by bovine neutrophils.
AB - To understand the process of neutrophil migration into mammary glands during
mastitis, secretion of MMP-9 by bovine neutrophils was investigated. The methods
of zymograms and RT-PCR were used to measure the secretory MMP-9 activity and its
gene transcription, respectively. Both MMP-9 protein and mRNA were found to be
expressed constitutively and greatly enhanced by PMA. However, the significant
increase in the enzyme activity was found after 1 ng/ml PMA treatment for 1 h,
while increasing MMP-9 mRNA transcription was only obvious after 1 ng/ml PMA
treatment for 3 h. Moreover, secretion of MMP-9 protein was not inhibited by
actinomycin D and cycloheximide. These results suggest that quick MMP-9 protein
release from bovine neutrophils by the stimulation of PMA was due to the
degranulation. As MMP-9 is an important proteinase in breakdown of the
extracellular matrix and can be rapidly secreted by neutrophils through
degranulation, it should play a critical role in the recruitment of neutrophils
into mammary glands in bovine mastitis.
PMID- 10195464
TI - Interaction between Salmonella typhimurium and phagocytic cells in pigs.
Phagocytosis, oxidative burst and killing in polymorphonuclear leukocytes and
monocytes.
AB - Interactions between Salmonella typhimurium and peripheral blood leucocytes from
healthy, Salmonella-free pigs were investigated in vitro. Both granulocytes and
monocytes phagocytized FITC-labelled heat-killed Salmonella bacteria as shown by
flow cytometry. Phagocytosis in whole blood and isolated leucocytes was measured
as acquired fluorescence in the leukocytes and was both time and dose related.
Living, serum-opsonized Salmonella bacteria induced a dose-dependent oxidative
burst in PMNs and monocytes as measured by luminol-enhanced chemiluminescence
(LC). When opsonized in normal serum the Salmonella bacteria, in the range of 2-5
x 10(7) cfu, induced a LC response in monocytes comparable to the level of
responses induced by phorbol myristate acetate (PMA) and opsonized zymosan, and
the Salmonella-induced response was only marginally reduced by superoxide
dismutase (SOD). Intracellular killing of Salmonella by monocytes was assessed
from plate colony counts of lysed monocytes and showed that Salmonella
typhimurium was able to survive and proliferate in adherent monocytes in vitro
despite a reduction in intracellular cfu during the first hour's incubation in
cells from some pigs. Experiments with the exhaustion of oxidative burst in non
adherent monocytes were performed by prestimulation with PMA, heat-killed
Salmonella or buffer. Prestimulation with PMA led to a strong reduction in
oxidative burst induced by living opsonized Salmonella bacteria, whereas
prestimulation with heat-killed bacteria gave rise to an enhanced response. In
these experiments intracellular killing of the added living Salmonella gave
variable results, in that monocytes from two out of three pigs showed no
essential change in intracellular bactericidal activity, but with cells from one
pig a less pronounced bactericidal activity was found after prestimulation with
PMA.
PMID- 10195466
TI - Cytotoxic interactions between bovine parainfluenza type 3 virus and bovine
alveolar macrophages.
AB - This paper describes an investigation of the cytotoxic activity of bovine
alveolar macrophages for parainfluenza type 3 (PI-3) virus-infected target cells,
using 51Cr release assays. Alveolar macrophages from uninfected calves were shown
to be capable of killing PI-3 virus infected cells without the presence of
antibody or complement (antibody-independent cell-mediated cytotoxicity). The
level of killing was shown to vary from animal to animal with specific lysis
values ranging from <5% to 70%. Presence of PI-3 virus antiserum was shown to
inhibit, rather than enhance macrophage cytotoxicity in a dose-dependent manner,
suggesting that bovine alveolar macrophages do not always exhibit antibody
dependent lysis in all cases. Following intranasal and intratracheal inoculation
of calves with PI-3 virus, the level of cytotoxicity by macrophages lavaged from
the lungs of the calves increased substantially, and by Day 5 post inoculation,
levels of 95% to 98% specific lysis were recorded. After Day 5, the killing
ability decreased rapidly to low levels. Cell-free lavage fluids, collected from
PI-3 virus infected and control calves at various times throughout the
experiment, were incubated with aliquots of an alveolar macrophage population
from an uninfected donor calf, which initially showed a low level of killing, and
were subsequently added to PI-3 virus infected target cells. The recorded levels
of cytotoxicity, mirrored those which were seen with the initial macrophage
effector cells from the infected and control animals, suggesting that macrophage
cytotoxicity was largely controlled by extracellular factors.
PMID- 10195465
TI - Up-regulation of inducible nitric oxide synthase mRNA in dogs experimentally
infected with Borrelia burgdorferi.
AB - The up-regulation of the inducible nitric oxide synthase (iNOS) mRNA was
determined by RT-PCR in 25 tissues each from 22 specific pathogen-free (SPF) dogs
experimentally infected with Borrelia burgdorferi by tick exposure and from five
uninfected control dogs. Using primers specific for a homologous region of the
human and canine iNOS sequence, and canine macrophage mRNA, we isolated and
partially sequenced canine iNOS. A sequence of 1775 bases was obtained and
primers specific for canine iNOS mRNA constructed to investigate the expression
of iNOS in dog tissues in response to infection with B. burgdorferi. In 12 out of
22 dogs infected with B. burgdorferi, acute lameness occurred within 55-82 days
after infection whereas the other 10 dogs showed no or only mild clinical signs
despite persistent infection up to Day 175. The numbers of iNOS mRNA-positive
tissues in dogs with acute lameness were significantly higher than in dogs
without lameness, while uninfected dogs showed only negligible iNOS expression.
Dogs with acute lameness also had higher numbers of borrelia-positive tissues as
well as higher scores in histopathological evaluations than infected dogs without
lameness. Our results show that the expression of iNOS mRNA is related to the
number of B. burgdorferi-positive tissues and the severity of inflammation as
assessed by histopathology. These results implicate an up-regulation of the iNOS
mRNA as part of the host's immune response to borrelia infection and a possible
role for NO in the pathogenesis of canine Lyme arthritis.
PMID- 10195467
TI - Fluid percussion brain injury exacerbates glutamate-induced focal damage in the
rat.
AB - The role of glutamate-mediated neuronal damage in neurotrauma remains
controversial. The cerebral levels measured in patients by microdialysis are
sufficient to kill neurons in culture, but not in the intact brain of the normal
rat. A synergistic effect between excitatory amino acid-mediated damage and other
posttrauma mechanisms must therefore be proposed, if glutamate is indeed a
significant cause of posttraumatic brain damage. The presence of such a
synergistic mechanism was therefore investigated by combining in vivo glutamate
perfusion and fluid percussion injury (FPI). Twenty-four adult male Sprague
Dawley rats were randomly assigned to three groups: (1) vehicle (n = 9): mock
cerebrospinal fluid (CSF) perfusion plus FPI; (2) glutamate + FPI (n = 9): 0.1 M
glutamate intracortical perfusion plus FPI; and (3) glutamate without FPI (n =
6). After preparation for central FPI, at a moderate level of injury (2 +/- 0.5
atm), glutamate or mock CSF perfusion was performed via a CMA/12 microdialysis
probe (3 mm). Animals were then perfusion fixed, under deep anesthesia, after 3-h
survival, for volumetric histopathology. The glutamate perfusion + FPI group
(2.42 +/- 1.63 mm3) produced a significantly bigger lesion than mock CSF
perfusion + FPI (0.063 +/- 0.41 mm3) and glutamate perfusion alone (1.00 +/- 0.47
mm3). Traumatic brain injury thus seems to enhance glutamate-mediated brain
damage, and this may be due to qualitative changes induced in ion channels and
receptors, such as the N-methyl-D-aspartate channel, after shear injury.
PMID- 10195468
TI - Effects of L-NAME and 7-NI on NOS catalytic activity and behavioral outcome after
traumatic brain injury in the rat.
AB - Traumatic brain injury (TBI) produces transient increases in constitutive nitric
oxide synthase (cNOS) activity and prolonged behavioral abnormalities. This study
investigated the effects of nitro-L-arginine-methyl ester (L-NAME) and 3-bromo-7
nitroindazole (7-NI) treatment on cNOS catalytic activity and sensorimotor
behavioral outcome after TBI. Rats underwent moderate (1.8-2.2 atm) parasagittal
fluid percussion brain injury (FPI). At 5 min after FPI, cNOS activity was
significantly increased within the damaged cerebral cortex of vehicle-treated
rats compared to the noninjured contralateral cortex (206.7 +/- 150.5 % of
contralateral, p < 0.01). Pretreatment with L-NAME and 7-NI significantly reduced
injury-induced cNOS activation (47.7 +/- 42.6 %, p < 0.05, and 96.16 +/- 12.76, p
< 0.05, respectively). Pretreatment with L-NAME and 7-NI also inhibited cNOS
activity within the contralateral noninjured cerebral cortex compared to vehicle
treated rats (L-NAME 43.7 +/- 12.47%, p < 0.05; 7-NI 36.8 +/- 7.47%, p < 0.05).
Furthermore, pretreatment with 7-NI, but not L-NAME, significantly reduced
forelimb placing sensorimotor deficits (3.14 +/- 1.07, p < 0.05) at 1 day after
TBI compared to vehicle-treated rats (5.38 +/- 0.42). These data indicate that
inhibition of injury-induced elevations in neuronal NOS activity has a beneficial
effect on neurological outcome after parasagittal FPI brain injury.
PMID- 10195469
TI - Regional changes in cerebral extracellular glucose and lactate concentrations
following severe cortical impact injury and secondary ischemia in rats.
AB - Traumatic brain injury (TBI) causes the brain to be more susceptible to secondary
insults, and the occurrence of a secondary insult after trauma increases the
damage that develops in the brain. To study the synergistic effect of trauma and
ischemia on brain energy metabolites, regional changes in the extracellular
concentrations of glucose and lactate following a severe cortical impact injury
were measured employing a microdialysis technique. Three microdialysis probes
were placed in center of the impact site, in an area adjacent to the impact site,
and in the contralateral parietal cortex, and perfused with artificial
cerebrospinal fluid (CSF) at 2 microl/min. Rats were assigned to one of the
following experimental groups (n = 7 per group): (1) combined impact injury and
secondary insult, (2) impact injury with sham secondary insult, (3) sham impact
with secondary insult, or (4) sham impact and sham secondary insult. The impact
injury was produced with a pneumatic impactor (5 m/sec, 3-mm deformation). One
hour following the impact injury, a secondary insult was produced by bilateral
carotid occlusion for 1 h. The impact injury resulted in a three- to fivefold
global increase in dialysate lactate concentrations, with a corresponding fall in
dialysate glucose concentration by 50% compared to no change in lactate or
glucose concentrations in sham-injured animals (p < .0001 for both lactate and
glucose). The secondary insult resulted in a second increase in dialysate lactate
and decrease in dialysate glucose concentration that was significantly greater in
the animals that had suffered the impact injury than in the sham-injured animals.
Ischemia and traumatic injury have synergistic effects on lactate accumulation
and on glucose depletion in the brain that probably reflects persisting ischemia,
but may also indicate mitochondrial abnormalities and inhibition of oxidative
metabolism.
PMID- 10195470
TI - Effect of moderate hypothermia on systemic and internal jugular plasma IL-6
levels after traumatic brain injury in humans.
AB - Moderate hypothermia may reduce subsequent neuronal damage after traumatic brain
injury. Interleukin (IL)-6 may have a role in the pathogenesis of traumatic
neuronal damage or repair. Using the enzyme-linked immunological sorbent assay
(ELISA), we serially measured IL-6 levels in plasma obtained from the radial
artery (systemic) and internal jugular vein (regional) in 13 cerebral trauma
patients who underwent hypothermia of 32-33 degrees C ranged from 4-9 days
postinjury and 10 head-injured patients who were maintained at normothermic
levels (36-37 degrees C). In both patient populations, surface cooling was used
since even in the normothermic group, cooling was needed to maintain patient
temperature in the normothermic range. All patients were mechanically ventilated
after injection of midazolam and vecuronium. The administration of these agents
were continued until the end of the study. Hypothermia was typically maintained
for four days, however, in some cases based upon CT findings and/or intra-cranial
pressure change, the duration was prolonged. No significant differences were
found between the two groups in age, gender and Glasgow Coma Scale upon
admission. Further, no differences were found in terms of the classification of
computed tomography findings or the occurrence of pupillary abnormalities on
admission. The patients in this study had not sustained either abdominal or
thoracic trauma. Before inducing hypothermia, IL-6 levels in the arterial and
internal jugular venous blood exceeded the normal range. Specifically, the
internal jugular plasma levels were significantly higher than those in the
arterial plasma. While IL-6 levels in the normothermic group did not decrease
even at 4 days postinjury, the plasma cytokine levels fell at both sites sharply
after moderate hypothermia. The cytokine suppression found in the hypothermic
group continued even after rewarming in these patients showing an improved
clinical course, but not in those whose condition worsened. In addition to these
changes in cytokine levels, the Glasgow Outcome Scale at 6 months postinjury was
significantly higher in the hypothermic group than in the normothermia group.
Based on the above, this clinical study with its small patient sample size
suggests the need for further prospective randomized studies to examine the role
of cytokine suppression in the beneficial effects of moderate hypothermia in
patients with traumatic brain injury.
PMID- 10195472
TI - Effects of six weeks of chronic ethanol administration on the behavioral outcome
of rats after lateral fluid percussion brain injury.
AB - This study examined the effects of 6 weeks of chronic ethanol administration on
the behavioral outcome in rats after lateral fluid percussion (FP) brain injury.
Rats were given either an ethanol liquid diet (ethanol diet-groups) or a pair-fed
isocaloric sucrose control diet (control diet groups) for 6 weeks. After 6 weeks,
the ethanol diet was discontinued for the ethanol diet rats and they were then
given the control sucrose diet for 2 days. During those 2 days, the rats were
trained to perform a beam-walking task and subjected to either lateral FP brain
injury of low to moderate severity (1.8 atm) or to sham operation. In both the
control diet and the ethanol diet groups, lateral FP brain injury caused beam
walking impairment on days 1 and 2 and spatial learning disability on days 7 and
8 after brain injury. There were no significant differences in beam-walking
performance and spatial learning disability between brain injured animals from
the control and ethanol diet groups. However, a trend towards greater behavioral
deficits was observed in brain injured animals in the ethanol diet group.
Histologic analysis of both diet groups after behavioral assessment revealed
comparable ipsilateral cortical damage and observable CA3 neuronal loss in the
ipsilateral hippocampus. These results only suggest that chronic ethanol
administration, longer than six weeks of administration, may worsen behavioral
outcome following lateral FP brain injury. For more significant behavioral and/or
morphological change to occur, we would suggest that the duration of chronic
ethanol administration must be increased.
PMID- 10195471
TI - Postpyloric enteral feeding costs for patients with severe head injury: blind
placement, endoscopy, and PEG/J versus TPN.
AB - This study describes the advantages and disadvantages of several forms of enteral
nutrition for patients with severe head injury (Glasgow Coma Scale Score [GCS],
<12). Included in the study are nasoenteric nutrition delivery using blind,
endoscopic, percutaneous endoscopic gastrostomy (PEG) and PEG with jejeunostomy
(PEG/J), and open jejeunostomy tube placement methods. These methods are compared
with parenteral delivery of nutrition. The study constituted a retrospective
analysis of the success rate of early enteral feedings by blind, endoscopic PEG
and PEG/J and by open jejeunostomy placement of small-bowel feeding tubes for 57
patients with severe head injury. The delivery cost of enteral nutrition per
intensive care unit day was compared to the delivery cost of parenteral nutrition
per intensive care unit day in the same group of patients. Fifty-three percent of
patients were adequately maintained nutritionally with nasoenteric delivery alone
and did not require parenteral feeding. The average number of days for initiation
of either enteral or parenteral feedings was 1.8 +/- 0.2 days from injury
[standard error of mean (SEM); range, 0-10 days]. An average of 3.3 days (range,
0-23 days) was required for feeding tube placement in all patients. For 70% of
patients, tube placement was completed within 48 h after injury. Full-strength,
full-rate enteral feedings were achieved by a mean of 4.9 days after injury. A
total of 128 feeding tubes were placed while the patients were in the intensive
care unit (ICU; 2.2 +/- 0.2 tubes per patient). Blind placement of feeding tubes
into the small bowel was rarely achieved without repositioning. Endoscopic tube
placement into the duodenum was achieved in 50% of patients, into the jejunum for
33% of patients, and into the stomach for 18% of patients. While in the intensive
care unit, patients received an average of 77 +/- 2% of their measured energy
expenditure (range, 57-114%). Eleven percent of patients experienced severe
gastrointestinal problems. Other problems were associated with the inability to
achieve or maintain access: dislodged tubes (30%), clogged or kinked tubes (21%),
and mechanical access problems (7 %). Seventy-one percent of patients in
barbiturate coma were able to tolerate early nasoenteric feedings. Aspiration
pneumonitis occurred equally among patients fed nasogastrically and those fed
nasoenterically. The overall aspiration rate was 14%. The cost of acute enteral
feeding was $170 per day and that for parenteral feeding, $308 per day. We
conclude that blind transpyloric feeding tube placement is difficult to achieve
in patients with severe head injury; endoscopically guided placement is a better
option. Endoscopic feeding tube placement most consistently allows for early
enteral nutritional support in severe head injured patients. Limitations include
the inability to establish and/or maintain enteral access, increased intracranial
pressure, unstable cervical spinal injuries, facial fractures, and dedication of
the physician to tube placement and monitoring.
PMID- 10195473
TI - Differential activation of microglia after experimental spinal cord injury.
AB - This study sought to experimentally clarify time-dependent, differential
microglial activation at various spinal cord locations in response to injury. The
spinal cords of Wistar rats were either sharply transected at the Th 11 or
subjected to compression at the same site. Immediately to 4 weeks after injury,
each spinal cord was fixed and cut into longitudinal frozen sections, and was
immunostained with OX42 for resident and activated microglia, OX-6 for activated
microglia, GFAP for activated astrocytes, and biotinylated BS-I, a lectin for
both resident and activated microglia. From three to 24 hours after injury, we
observed a narrow belt around the transection site in which OX42 positive
microglia were dramatically reduced in number, or often absent. BS-I labeling of
the zone disclosed the rapid transformation of those microglia possessing typical
antler-like processes to macrophage-like cells. At day 1 and thereafter, the zone
of reduced OX42 immunoreactivity was gradually replaced by macrophage-like OX42
positive round cells, and the lesion itself was ultimately capped by fibrogliotic
scar tissue. By 2-4 weeks postinjury, another phase of microglial activation was
observed in those white matter tracts undergoing Wallerian degeneration. These
microglia characterized by the presence of newly-expressed MHC class II antigens.
We posit that the decreased OX42 immunoreactivity suggests that CR3 is quickly
saturated by activated iC3b and internalized, but not down-regulated. The trigger
for this transformation most likely occurs through signaling by iC3b-saturated
CR3. In contrast, microglia activation along those degenerating tracts undergoing
Wallerian degeneration does not appear to be CR3-related, as the CR3 is
upregulated. These observations indicate microglia have at least two different
spatial and temporal patterns of activation. One is rapid and most likely
involves the blood-borne complement activating system. The other accompanies
Wallerian degeneration and is independent of the blood-borne complement system.
PMID- 10195474
TI - Functional recovery from cortical hemiplegia in the rat: effects of a
callosotomy.
AB - The present work aimed at studying the participation of the homologous
contralateral zone to a unilateral somatomotor cortex lesion, once the animals
had showed a significant functional recovery. We studied recovery of coordinated
walking after unilateral motor cortex aspiration in rats. A callosotomy was
performed 20 days after the initial lesion, without significant effects. We
conclude that after this time period, the intact hemisphere plays no role in the
recovery process, suggesting that at this time point recovery does not depend on
the integrity of corpus callosal fibers at this rostral-caudal level.
PMID- 10195475
TI - A randomized controlled trial of buffered lidocaine for local anesthetic
infiltration in children and adults with simple lacerations.
AB - This study assessed the efficacy of buffered lidocaine in children and adults for
the repair of simple lacerations. We compared plain lidocaine (PL) with buffered
lidocaine (BL) in a prospective, randomized, double-blind, placebo controlled
trial. Children had a 10-point pain score assessed by a nurse using predetermined
behavior criteria, and a visual analog pain score (VAS) as perceived by the
parent. Adult visual analog scores were self reported. In 135 adults, the median
VAS was 2.1 for PL and 2.0 for BL. In 136 children, the median nurse-rated pain
score was 4.5 for both PL and BL. The parent's median VAS was 4.5 for PL and 4.0
for BL. In contrast to previous studies, we conclude that buffered lidocaine does
not reduce infiltration pain in children or adults.
PMID- 10195476
TI - Utilization of lumbosacral spine radiographs for the evaluation of low back pain
in the emergency department.
AB - We sought to determine how often Emergency Physicians (EPs) order plain
radiographs (XRs) of the lumbosacral spine in evaluating patients with low back
pain (LBP). In addition, we sought to determine what history and physical
examination findings were statistically associated with the use of an XR.
Patients evaluated in our Emergency Department (ED) between April 1, 1995 and
September 30, 1995 for LBP were identified retrospectively by their ICD-9
discharge code. The ED record was reviewed, and an odds ratio (OR) was calculated
for each of several history and physical examination findings, to determine which
of them increased the likelihood of having an XR. Forty of 214 patients (19%)
with LBP had an XR done. Patient characteristics associated with the use of an XR
were: a positive straight leg examination, age > 50 years, a history of trauma,
and vertebral tenderness. In this series, only a small minority of patients with
LBP had an XR done as part of their ED evaluation. The choice of which patients
to image was determined by history and physical examination findings. We conclude
that the EPs we studied are evaluating LBP as conservatively, if not more so,
than physicians in other specialties.
PMID- 10195477
TI - Phytophotodermatitis: the other "lime" disease.
AB - Phytophotodermatitis is a skin eruption that occurs after contact with
photosensitizing compounds in plants and exposure to UV light. There are two
common presentations of phytophotodermatitis. Acutely, erythema and vesiculation
similar to a severe sunburn are noted. After resolution of the inflammation, the
involved skin has marked hyperpigmentation. Many plants have been identified that
contain furocoumarins (psoralens), including limes, lemons, and celery. We
present a patient with an acute phototoxic eruption and hyperpigmentation after
contact with limes during a beach vacation.
PMID- 10195478
TI - Acute abdominal pain and urgency to defecate in the young and the old: a useful
symptom-complex?
AB - In the belief that "pattern recognition" is an important first step of the
diagnostic process, we report our observation of an uncommon and heretofore
poorly documented symptom-complex in 10 patients, and suggest that the
constellation of abdominal pain and urgency to defecate in the acutely ill
surgical patient should raise the diagnostic possibility of intra-abdominal
bleeding. In our experience, this is statistically likely to be associated with a
ruptured abdominal aortic aneurysm in the old and a ruptured ectopic pregnancy in
the young.
PMID- 10195479
TI - A case of urachal remnant presenting as acute abdominal pain.
AB - A 30-year-old male presented to the Emergency Department, over sequential visits,
with abdominal complaints. The patient's presenting history and physical
examination were mistakenly diagnosed variously as gastroenteritis, omphalitis,
and appendicitis. Ultimately, the diagnosis of urachal fistula was made at
surgery. This case is discussed in light of prior published experiences with this
disease entity.
PMID- 10195480
TI - Epidural pneumatosis associated with spontaneous pneumomediastinum: case report
and review of the literature.
AB - Epidural pneumatosis rarely has been reported in association with spontaneous
pneumomediastinum. We report a case of an asymptomatic 24-year-old male who
presented after forceful vomiting with both findings. The patient recovered
uneventfully without residual signs or symptoms. We discuss spontaneous
pneumomediastinum as well as epidural pneumatosis and review reported cases in
the literature.
PMID- 10195481
TI - Coccygeal fracture and Paget's disease presenting as acute cauda equina syndrome.
AB - Paget's disease of bone affects a significant percentage of adult and elderly
patients. Although generally asymptomatic, the inflammatory changes and
hypervascularity of the affected bone is prone to pathologic fracture and
resultant hemorrhage. Epidural hematoma is well-described with vertebral
fractures and can present as acute cauda equina syndrome. We describe a case in
which an elderly female with Paget's disease sustained a minor coccygeal fracture
and developed local hemorrhage and edema, which caused a sacral plexopathy that
presented identical to acute cauda equina syndrome. A literature review will
follow.
PMID- 10195482
TI - A new hazard for windsurfers: needlefish impalement.
AB - Marine-related injuries and envenomations are common to the coastal physician.
Needlefish injuries, which occur almost exclusively in the Indo-Pacific region,
have not previously been reported along the Atlantic seaboard. This case report
describes a penetrating injury to the lower extremity from a needlefish.
Treatment is guided by general resuscitative procedures as well as antibiotic
therapy directed against infections unique to the marine environment.
PMID- 10195483
TI - Emergency department management of occupational exposures to HIV-infected fluids.
AB - The emergency department is where many healthcare workers will seek medical
advice and care after a potential exposure to bodily fluids contaminated with the
human immunodeficiency virus (HIV). The estimated risk of HIV infection in
healthcare workers with percutaneous exposures to HIV-infected blood is estimated
at 0.3% to 0.32%. Zidovudine (AZT) post-exposure prophylaxis has been associated
with a 79% reduction in the risk of seroconversion in a case-control study
sponsored by the Center for Disease Control and Prevention (CDC), and has become
part of the standard prophylactic treatment for patients with occupational HIV
exposure. This article reviews the current CDC recommendations as well as our
institutional practice guidelines for the management of healthcare workers who
are exposed to potential or confirmed HIV-infected fluids.
PMID- 10195484
TI - Two cases of neuroblastoma presenting to the emergency department.
AB - Neuroblastoma is the second most common malignant solid tumor in the pediatric
population. Recent advances in treatment options and identification of prognostic
subsets have made early detection important. Early classification into a
favorable stage and subset may carry a 10-year survival of about 90% (1). With
newer treatment regimens, the probability of long-term survival in patients with
metastatic disease has also increased about fourfold since 1979 (2). Emergency
physicians can contribute to improved morbidity and mortality with appropriate
evaluation and disposition of the patient presenting with neuroblastoma. Two
patients, a 6-month-old and a 2-week-old, presented to the Emergency Department
with weakness. Both had a presumptive diagnosis of neuroblastoma made by the
emergency physician. A brief discussion of the incidence, presentation, and
diagnosis of neuroblastoma follows.
PMID- 10195485
TI - Intussusception following a baby walker injury.
AB - Serious abdominal injury as a result of a fall in a baby walker has not been
previously reported. We present the case of a 13-month-old boy who developed
intussusception following a fall down five stairs in a baby walker. Attempted
hydrostatic reduction was unsuccessful. At operation, a bowel wall hematoma,
serving as a lead point, was identified. This case adds another type of injury to
the list of those previously associated with baby walker use.
PMID- 10195486
TI - Organophosphate poisoning in Perth, Western Australia, 1987-1996.
AB - This study aimed to review the presentation and management of patients with
organophosphate poisoning admitted to the four tertiary teaching hospitals in
Perth, Western Australia, over a 10-year period. The case notes of all 69
patients admitted with a discharge diagnosis of organophosphate poisoning were
reviewed. Twenty-two of 25 patients (88%) attempting suicide were admitted to
Intensive Care Units (ICUs), with a mean stay of 7 days (range 1-25 days). All
but one were men, and two died. The 44 patients with accidental exposure were
mainly children and had a mean stay of 2 days, with only seven going to the ICU.
All survived. Complications overall included respiratory failure, convulsions,
and aspiration pneumonia. Intubation and ventilation were required in 11 patients
(16%), with a mean ventilation duration of 6 days (range 1-25 days). We conclude
that deliberate ingestion of organophosphates is considerably more toxic than
accidental exposure. Men aged 30-50 years were the most likely to attempt suicide
with these agents and had prolonged ICU admissions with significant complications
and mortality.
PMID- 10195487
TI - Incidence of aspiration pneumonia in intubated patients receiving activated
charcoal.
AB - Several case reports and animal studies raise concerns over the risk of
aspiration pneumonia when administering activated charcoal (AC) to intubated
patients. Therefore, we sought to determine the incidence of aspiration pneumonia
in intubated overdose patients who then received AC. We conducted a retrospective
review from January 1994 to April 1997 of intubated patients who then received
AC. Patients were transferred to, or primarily treated at, an 843-bed tertiary
medical center with an annual emergency department volume of 100,000 patients.
Objective evidence of infiltrate on chest radiograph during initial 48 h of
hospitalization was used to determine the incidence of aspiration pneumonia.
Patients with known preexisting pneumonia or with administration of AC before
intubation were excluded. There were 64 patients identified. Fourteen were
excluded for clinical aspiration before intubation, receiving activated charcoal
before intubation, or abnormal immediate post-intubation chest radiographs. The
remaining 50 patients, ages 1-64 years, 33% male, overdosing on a large variety
of substances, required acute intubation and then received AC. Only two patients
of these 50 (4%) with initial negative radiographs developed a new infiltrate
after intubation and AC. Administration of AC to intubated overdose patients is
associated with a low incidence of aspiration pneumonia.
PMID- 10195488
TI - Dextromethorphan- and pseudoephedrine-induced agitated psychosis and ataxia: case
report.
AB - Pseudoephedrine and dextromethorphan are therapeutic constituents of numerous
commonly used, over-the-counter cough and cold preparations. Although this drug
combination is generally considered quite safe if utilized in recommended doses,
overmedication or overdose can result in serious neurologic and cardiovascular
abnormalities that occasionally can be life-threatening. We present a case of a 2
year-old child who developed hyperirritability, psychosis, and ataxia after being
overmedicated with a pseudoephedrine/dextromethorphan combination cough
preparation, and discuss probable mechanisms of toxicity and risk factors for
adverse events.
PMID- 10195489
TI - Cardiovascular toxicity after ingestion of "herbal ecstacy".
AB - "Herbal Ecstacy" (sic) is an alternative drug of abuse usually containing both
ephedrine and caffeine. Our literature search did not reveal any other reported
cases of cardiovascular toxicity related to herbal "drugs of abuse." A case of
cardiovascular toxicity following the ingestion of herbal ecstacy is presented. A
21-year-old male presented to the emergency department with an initial blood
pressure of 220/110 mmHg and ventricular dysrhythmias after ingesting four
capsules of herbal ecstacy. He was treated with lidocaine and sodium
nitroprusside, and his symptoms resolved in 9 h. The pathophysiology and clinical
course of ephedrine toxicity are discussed. Emergency physicians should consider
ephedrine preparations in the differential diagnosis of patients presenting with
a sympathomimetic toxidrome. Drugs of abuse containing "herbal" products can
produce serious morbidity and mortality.
PMID- 10195490
TI - Balcony collapse at the University of Virginia graduation: what hath Jefferson
wrought?
AB - The purpose of this report is to describe the emergency medical response to a
disaster caused by the collapse of a balcony in Pavilion I on the Lawn of the
University of Virginia during graduation. The emergency medical response to
rescue of the injured was hindered by five major factors: (1) a metal linked
chain blocked access of rescue vehicles, (2) inability to identify an emergency
medical command officer, (3) failure to transfer injured patients with stable
vital signs and secured to backboards to a triage area away from the scene of the
accident, (4) ineffective crowd control, and (5) the failure to delay procession
until completion of patient transport from the disaster site. Sixteen people were
injured in the accident and one patient died. The cause of the accident was the
absence of a redundant architectural support system for the balcony.
PMID- 10195491
TI - Can noncontrast helical computed tomography replace intravenous urography for
evaluation of patients with acute urinary tract colic?
AB - The objective of this study was to determine whether helical computed tomography
(CT) performed without oral or intravenous contrast agents is accurate in the
evaluation of patients with suspected acute renal colic. One hundred consecutive
patients with suspected renal colic or ureteral colic were referred by our
institution's emergency department for unenhanced helical CT scans. We reviewed
the original radiographic report for each patient and recorded the size and
location of ureteral calculi and other concurrent urinary tract calculi, if any.
We also recorded the presence or absence of hydronephrosis, hydroureter,
perinephric edema, and periureteral edema. A total of 49 patients had ureteral
calculi, 17 patients had only renal calculi, and 34 patients had no stones. Forty
nine patients had ureteral calculi, and 40 (82%) of these 49 patients had
associated CT signs including hydroureter and periureteral edema. Calculi were
present in the proximal ureter in 11 patients, the midureter in seven patients,
and the distal ureter including ureterovesical junction in 31 patients. Calculi
were seen elsewhere in the urinary tract and renal pelvis in 44 patients. Other
diagnostic tests and stone passage were used to confirm the CT diagnosis of
ureteral stones. The sensitivity and specificity of helical CT in evaluating
ureteral calculi were 100% and 94%, respectively. Sixteen extraurinary lesions
were detected in 34 patients who had no urinary calculi. Most extraurinary
lesions (81%) were deemed the cause of acute flank pain. The room time for CT
averaged 26 min, compared to 69 min for intravenous urography (IVU). The charge
for CT was $600 compared to $400 for IVU in our institution. Unenhanced helical
CT was fast and accurate in determining the cause of colic and proved to be
highly accurate for emergency situations.
PMID- 10195492
TI - Anterior process fracture or calcaneus secundarius: a case report.
AB - Avulsion of the anterior process of the calcaneus accounts for nearly 15% of
calcaneal fractures according to some sources. Yet, this fracture rarely has been
reported in the radiology literature. Lateral plain radiography of the foot may
demonstrate an ossific structure, distinct from the distal end of the calcaneus,
overlying the head of the talus. However, the fracture may be particularly subtle
and go undetected on plain radiography. Furthermore, it may be mistaken for the
calcaneus secundarius (CS), an accessory ossicle of the anterior facet of the
calcaneus identified in up to 5% of the population during cadaveric studies. This
article describes the physical and radiological findings in a patient with an
anterior process fracture and how this fracture can be distinguished from the CS.
PMID- 10195493
TI - Cerebral ventricular shunts.
AB - Cerebral ventricular shunts are siphoning devices used to treat hydrocephalus.
They are placed within cerebral ventricles and peripheral cavities such as the
ventricular atrium or peritoneal cavity. Complications include obstruction of
cerebral spinal fluid (malfunction) and infection. Morbidity and mortality rates
are high when shunt malfunction and infection are not treated emergently. This
report summarizes the physical examination of patients with ventricular shunts,
reviews the type of shunts commonly used, discusses shunt malfunctions (causing
overshunting or undershunting of cerebrospinal fluid) and infections, and makes
recommendations concerning empiric antibiotic therapy for shunt infection. The
technique of tapping a shunt is presented for management of patients with
elevated intracranial pressure that does not respond to non-invasive maneuvers to
lower the pressure.
PMID- 10195494
TI - Use of intramuscular midazolam for status epilepticus.
AB - Although intravenous (i.v.) administration of antiepileptic drugs is the
preferred route of therapy in status epilepticus, intramuscular (i.m.) delivery
may provide a valuable alternative when there are obstacles to venous access.
Compared to other treatment options such as rectal drug administration, which is
as challenging as the i.v. route in a convulsing patient, the i.m. route is
easier and less invasive. The two most commonly used first-line anticonvulsants,
diazepam and lorazepam, may be administered i.m., but are absorbed from the i.m.
site more slowly than midazolam. Midazolam, a fairly new benzodiazepine, is a
potent anticonvulsant with a fast onset of effect. Because of its water
solubility, midazolam is rapidly absorbed from the injection site and has
excellent local tolerability. The pharmacodynamic effects of midazolam can be
seen within seconds of its administration, and seizure arrest is usually attained
within 5 to 10 min. Case reports and a recent randomized trial that demonstrate
the successful use of i.m. midazolam in the termination of epileptic seizures are
reviewed.
PMID- 10195495
TI - Recurrent pleuritic chest pain.
PMID- 10195497
TI - Radiographic findings in intussusception.
PMID- 10195496
TI - Chest radiograph in pulmonary embolus.
PMID- 10195498
TI - Spontaneous pneumopericardium in an eight-year-old child.
PMID- 10195499
TI - The houses that Ruth and Jefferson built.
PMID- 10195500
TI - Drug development: an opportunity for unique alliances between industry and
academia.
PMID- 10195501
TI - The goals of medicine.
PMID- 10195502
TI - Re: Case presentations on angioedema.
PMID- 10195503
TI - Re: Ludwig's angina, Bramwell et al.
PMID- 10195504
TI - Assessment of pain management skills in emergency medicine residents: the role of
a pain education program.
AB - A prospective study of Emergency Medicine (EM) residents was conducted over two
consecutive 1-month periods at a rural tertiary-care teaching hospital with a
residency in EM to evaluate the effect of a 4-h pain management education program
on the assessment and management of acute pain in the emergency department (ED).
All patients presenting to the ED with an acute, painful condition were eligible
to participate in the survey. Patients were excluded if they had taken any pain
medication within 4 h of presenting to the ED, or had any condition requiring
immediate resuscitation, suspected cardiac pain, or pain from a potential
surgical abdomen. Baseline and 30-min pain scores were evaluated using a 100-mm,
unnumbered visual analog scale (VAS). A 4-h pain management educational program
(EP) aimed toward the EM residents was conducted. Comparisons were made with
respect to the overall treatment of pain as evaluated by the change in VAS score
between baseline and 30 min as well as the global assessment of treatment. A
total of 126 surveys were completed, 54 before (Group 1) and 72 after (Group 2)
the EP. The mean deltaVAS score for patients in Group 2 was significantly better
than the deltaVAS score for patients in Group 1. Only 65% of the patients studied
before the EP had significant reduction in their pain scores after 30 min in the
ED; after institution of the EP, 92% had a significant reduction in their pain
scores at 30 min. Similarly, a significant improvement was seen in the patients'
global evaluation of treatment after the educational program was instituted. It
appears that the use of a 4-h educational program on pain assessment and
management directed toward EM residents in their training can improve their
skills at recognizing and treating painful conditions.
PMID- 10195505
TI - Assessing emergency medicine resident communication skills using videotaped
patient encounters: gaps in inter-rater reliability.
AB - We report on a process for assessing the communication skills of emergency
medicine residents that includes 1) a faculty development initiative; 2)
videotaping of actual resident-patient encounters in the emergency department;
and 3) creation of an observation instrument for evaluating communication
behaviors. We tested this observation instrument for inter-rater reliability,
finding moderate-to-high agreement for only 11 of 32 items. These related to
personal introductions, conflict management, nonverbal communication, and overall
performance. There was poor or no agreement for behaviors related to establishing
rapport, gathering information, and contracting or informing. Challenges of
assessing interpersonal skills of emergency medicine residents are discussed.
PMID- 10195506
TI - The facilitated pediatric resuscitation room.
AB - Pediatric resuscitation is challenging for the emergency physician because the
diverse range in the age and size of the patients encountered complicates the
appropriate selection of medications, equipment, and supplies. The following
enhancements in the pediatric resuscitation room were made to facilitate
effective management of critically ill neonates and children: 1) expanding the
concept of the Broselow tape as the central color theme of organization of all
medication doses and equipment; 2) use of a large, simplified, color-coded wall
chart to define patient parameters; 3) color-coded equipment; 4) adjustable
"break-away" resuscitation stretcher; and 5) equipment suspended from the
ceiling: a) radiant warmer; b) suction, oxygen, and electricity; c) cardiac
monitor and fluid controller; d) X-ray unit. These changes give the resuscitation
team greater accessibility to both the patient and the needed resuscitation
supplies.
PMID- 10195507
TI - The potential for pain.
PMID- 10195509
TI - Isoflurane and sodium nitroprusside reduce the depressant effects of protamine
sulfate on isolated ischemic rat hearts.
AB - The administration of protamine sulfate (protamine) to reverse the action of
heparin is associated with adverse reactions. We studied the effects of protamine
and isoflurane on isolated, perfused rat hearts previously subjected to
cardioplegic ischemia. Hearts were perfused with oxygenated Krebs-Henseleit (KH)
solution for 30 min, then subjected to cardioplegic ischemia for 30 min (KCl 16
mEq/L at 31 degrees C) and 5 min reperfusion. Drug exposure lasted 15 min, and
the recovery period was 60 min. Test groups were control, protamine (10
microg/mL), isoflurane (1.5%), protamine +/- isoflurane, sodium nitroprusside
(SNP) (2.5 ng/mL), and SNP +/- protamine. Left ventricular developed pressure
(LVP), coronary flow, and myocardial oxygen consumption were depressed by
protamine to 30% +/- 4%, 47% +/- 4%, and 39% +/- 4% of baseline (P < 0.001 versus
control), respectively. Isoflurane and SNP afforded partial protection from the
effects of protamine: LVP was 57% +/- 5% and 51% +/- 3% of baseline, respectively
(P < 0.05 versus protamine alone and control); coronary flow was 70% +/- 6% and
97% +/- 12% of baseline, respectively (P < 0.05 versus protamine alone; P < 0.05
for isoflurane versus control); and O2 consumption was 69% +/- 6% and 88% +/- 15%
of baseline, respectively (P < 0.05 versus protamine; P < 0.05 for isoflurane
versus control). In this model, protamine-induced myocardial depression and
coronary vasoconstriction were less pronounced in the presence of either
isoflurane or SNP. IMPLICATIONS: We examined the interactions of isoflurane,
sodium nitroprusside, and protamine in a rat heart model and found that both
isoflurane and sodium nitroprusside partially protect the heart from the
depressant effects of protamine. This finding is significant, as these drugs are
often used in heart surgery.
PMID- 10195508
TI - High thoracic epidural anesthesia, but not clonidine, attenuates the
perioperative stress response via sympatholysis and reduces the release of
troponin T in patients undergoing coronary artery bypass grafting.
AB - In this prospective study, we evaluated whether high thoracic epidural anesthesia
(TEA) or i.v. clonidine, in addition to general anesthesia, affects the
cardiopulmonary bypass- and surgery-associated stress response and incidence of
myocardial ischemia by their sympatholytic properties. Seventy patients scheduled
for elective coronary artery bypass graft (CABG) received general anesthesia with
sufentanil and propofol. TEA was randomly induced before general anesthesia and
continued during the study period in 25 (anesthetized dermatomes C6-T10). Another
24 patients received i.v. clonidine as a bolus of 4 microg/kg before the
induction of general anesthesia. Clonidine was then infused at a rate of 1 microg
x kg(-1) x h(-1) during surgery and at 0.2-0.5 microg x kg(-1) x h(-1)
postoperatively. The remaining 21 patients underwent general anesthesia as
performed routinely (control). Hemodynamics, plasma epinephrine and
norepinephrine, cortisol, the myocardial-specific contractile protein troponin T,
and other cardiac enzymes were measured pre- and postoperatively. During the
preoperative night and a follow-up of 48 h after surgery, five-lead
electrocardiogram monitoring was used for ischemia detection. Both TEA and
clonidine reduced the postoperative heart rate compared with the control group
without jeopardizing cardiac output or perfusion pressure. Plasma epinephrine
increased perioperatively in all groups but was significantly lower in the TEA
group. Neither TEA nor clonidine affected the increase in plasma cortisol. The
release of troponin T was attenuated by TEA. New ST elevations > or = 0.2 mV or
new ST depression > or = 0.1 mV occurred in > 70% of the control patients but
only in 40% of the clonidine group and in 50% of the TEA group. We conclude that
TEA (but not i.v. clonidine) combined with general anesthesia for CABG
demonstrates a beneficial effect on the perioperative stress response and
postoperative myocardial ischemia. IMPLICATIONS: Thoracic epidural anesthesia
combined with general anesthesia attenuates the myocardial sympathetic response
to cardiopulmonary bypass and cardiac surgery. This is associated with decreased
myocardial ischemia as determined by less release of troponin T. These findings
may have an impact on the anesthetic management for coronary artery bypass
grafting.
PMID- 10195510
TI - Nitric oxide synthesis inhibition modifies the cardiotoxicity of tetracaine and
lidocaine.
AB - Suppression of nitric oxide (NO) production alters the toxicity of cocaine and
bupivacaine. We undertook this study to determine whether the systemic toxicity
of two other local anesthetics that differ in antiarrhythmic activity, plasma
clearance, and biotransformation are similarly affected by nitric oxide synthase
(NOS) inhibition. Sprague-Dawley rats anesthetized with 70% N2O and 0.5%
halothane mixed with O2 were pretreated with saline (0.2 mL x kg(-1) x min(-1)
i.v.) or N(omega)-nitro-L-arginine methyl ester (L-NAME; a competitive inhibitor
of NOS) (2 mg x kg(-1) x min(-1) i.v.) for 30 min. The animals were then given
tetracaine (3 mg x kg(-1) x min(-1) i.v.) or lidocaine (8 mg x kg(-1) x min(-1)
i.v.) until cardiac arrest (asystole). Doses of lidocaine or tetracaine that
produced arrhythmias, seizures, isoelectric encephalogram, and asystole were
determined. Hemodynamic recordings were performed throughout the experiments, and
plasma was collected to measure the concentration of lidocaine or tetracaine. L
NAME decreased tetracaine and lidocaine doses that produced arrhythmias (> or = 2
degrees atrioventricular conduction block) (tetracaine 14 +/- 2 mg/kg; lidocaine
102 +/- 9 mg/kg) versus saline treatment (tetracaine 28 +/- 2 mg/kg; lidocaine
136 +/- 9 mg/kg; P < 0.05). The tetracaine and lidocaine doses required to
produce asystole were also smaller in animals with L-NAME pretreatment than those
in saline-pretreated animals. L-NAME reduced the arrhythmia dose of tetracaine
more than the arrhythmia dose of lidocaine (28 of 14 = 2.0 fold and 136 of 102 =
1.3-fold). The plasma concentration of lidocaine, but not tetracaine, was
significantly higher at each sample time in L-NAME-pretreated animals than in
saline-pretreated animals. Inhibition of NOS by L-NAME enhances the
cardiotoxicity of lidocaine and tetracaine, with a greater effect on tetracaine
than on lidocaine. Altered drug clearance by L-NAME was insufficient to explain
these findings because L-NAME pretreatment increased the plasma levels of only
lidocaine, not tetracaine. IMPLICATIONS: Inhibition of nitric oxide production in
rats markedly enhances the cardiovascular toxicity of lidocaine and tetracaine.
Altered drug clearance by N(omega)-nitro-L-arginine methyl ester was insufficient
to explain these findings because N(omega)-nitro-L-arginine methyl ester
pretreatment increased the plasma levels of only lidocaine, not tetracaine.
PMID- 10195511
TI - The cost-effectiveness of methohexital versus propofol for sedation during
monitored anesthesia care.
AB - We designed this study to test the hypothesis that methohexital is a cost
effective alternative to propofol for sedation during local anesthesia. Sixty
consenting women undergoing breast biopsy procedures under local anesthesia were
randomly assigned to receive an infusion of either propofol (50 microg x kg(-1) x
min(-1)) or methohexital (40 microg x kg(-1) x min(-1)). The sedative infusion
rate was titrated to maintain an observer's assessment of alertness/sedation
(OAA/S) score of 3 (with 1 = awake/alert to 5 = asleep). Fentanyl 25 microg i.v.
was administered as a "rescue" analgesic during the operation. We assessed the
level of sedation (OAA/S score), vital signs, time to achieve an OAA/S score of 3
at the onset and a score of 1 after discontinuing the infusion, discharge times,
perioperative side effects, and patient satisfaction. The direct cost of
methohexital was lower than that of propofol, based on the milligram dosage
infused during the operation. The sedative onset (to achieve an OAA/S score of 3)
and the recovery (to return to an OAA/S score of 1) times, as well as discharge
times, did not differ between the two groups. Patients receiving methohexital had
a significantly lower incidence of pain on initial injection compared with those
receiving propofol (10% vs 23%). Because the use of methohexital (29.4 +/- 2.7
microg x kg(-1) x min(-1)) for sedation during breast biopsy procedures has a
similar efficacy and recovery profile to that of propofol (36.8 +/- 15.9 microg x
kg(-1) x min(-1)) and is less costly based on the amount infused, it seems to be
a cost-effective alternative to propofol for sedation during local anesthesia.
However, when the cost of the drug infused and drug wasted was calculated, there
was no difference in the overall drug cost. IMPLICATIONS: When administered to
maintain a stable level of sedation during local anesthesia, methohexital is an
acceptable alternative to propofol. However, the overall drug costs were similar
with the two drugs.
PMID- 10195512
TI - Postoperative analgesia for outpatient arthroscopic knee surgery with
intraarticular clonidine.
AB - Intraarticular (i.a.) local anesthetics are often used for the management and
prevention of pain after arthroscopic knee surgery. Clonidine prolongs the
duration of local anesthetics. We designed this study to determine whether
clonidine added to an i.a. injection would result in an analgesic benefit. Fifty
patients were randomly assigned to one of five groups that received clonidine
(either via the subcutaneous or i.a. route) or saline placebo with or without
i.a. bupivacaine, as follows: Group 1 received 30 mL of 0.25% bupivacaine i.a.;
Group 2 received 30 mL of 0.25% bupivacaine with clonidine (1 microg/kg) i.a.;
Group 3 received 30 mL of 0.25% bupivacaine i.a. and subcutaneous clonidine (1
microg/kg); Group 4 received 30 mL of 0.25% bupivacaine with epinephrine (5
microg/mL) i.a.; and Group 5 received clonidine (1 microg/kg) in 30 mL of saline
i.a.. The results of this study revealed a significant difference in analgesia
from the i.a. administration of clonidine. The group who received a combination
of i.a. bupivacaine and clonidine had a significantly decreased need for oral
postoperative analgesics and an increased analgesic duration (P < 0.0001). We
conclude that i.a. clonidine improved comfort in patients undergoing knee
arthroscopy. IMPLICATIONS: The intraarticular administration of clonidine along
with bupivacaine results in a significant improvement in analgesia compared with
either drug alone. There was an increased time to first analgesic request and a
decreased need for postoperative analgesics.
PMID- 10195513
TI - Use of remifentanil during anesthetic induction: a comparison with fentanyl in
the ambulatory setting.
PMID- 10195514
TI - Tracheal intubation of healthy pediatric patients without muscle relaxant: a
survey of technique utilization and perceptions of safety.
AB - We conducted a survey of Society for Pediatric Anesthesia anesthesiologists
practicing within the United States to determine the frequency of tracheal
intubation of healthy infants and children using an inhaled anesthetic without
muscle relaxation (IAWMR). We also examined reasons for the use of this
technique. Of all responders who listed their most often used technique for
tracheal intubation of healthy infants and children, IAWMR was chosen over
intubation with a muscle relaxant by 38.1% and 43.6%, respectively.
Anesthesiologists who most often used IAWMR for tracheal intubation of healthy
infants and children had over twice the odds (odds ratio [OR] 2.30 for infants,
95% confidence interval [CI] 1.18-4.50; P = 0.015) of classifying their own
practice as nonacademic, and one-third the odds (OR 0.34 for infants, 95% CI 0.17
0.68; P = 0.002) of conducting more than half of their cases in a supervisory
role. Anesthesiologists who use IAWMR to tracheally intubate healthy pediatric
patients most commonly selected as their reasons the lack of need for a muscle
relaxant and the desire to avoid both succinylcholine and the excessive duration
of nondepolarizing muscle relaxants. IMPLICATIONS: Inhaled anesthetic without
muscle relaxation is the most often used method of intubation for more than one
third of Society for Pediatric Anesthesia anesthesiologists when tracheally
intubating healthy, fasted pediatric patients undergoing elective procedures. The
frequency of this practice seems to be highest in nonacademic practices.
PMID- 10195515
TI - Tracheal extubation of deeply anesthetized pediatric patients: a comparison of
isoflurane and sevoflurane.
AB - We studied the emergence characteristics of unpremedicated children tracheally
extubated while deeply anesthetized ("deep extubation") with isoflurane or
sevoflurane. Forty children were assigned to one of two groups, Group I or Group
S. At the end of the operation, Group I patients were extubated while breathing
1.5 times the minimum alveolar anesthetic concentration (MAC) of isoflurane.
Group S patients were tracheally extubated while breathing 1.5 times the MAC of
sevoflurane. Recovery characteristics and complications were noted. Group S
patients were arousable sooner than Group I patients (10.1 + 6.5 vs 16.3 + 9.9
min). Later arousal scores and times to discharge were the same. There were no
serious complications in either group. Breath-holding was more common in Group I.
We conclude that the overall incidence of airway problems and desaturation
episodes was similar between groups. Emergency delirium was common in both groups
(32% overall: 40% for Group I, 25% for Group S). IMPLICATIONS: Deep extubation of
children can be safely performed with either isoflurane or sevoflurane. After
deep tracheal extubation, airway problems occur but are easily managed. Return to
an arousable state occurred more quickly with sevoflurane, although time to
meeting discharge criteria was not different between the two groups. Emergence
delirium occurs frequently with either technique.
PMID- 10195516
TI - The use of lidocaine for preventing the withdrawal associated with the injection
of rocuronium in children and adolescents.
AB - We designed this study to examine the incidence and degree of movement after the
administration of rocuronium in children and adolescents and to measure the
treatment effect of lidocaine for its prevention. One hundred patients (aged 5-18
yr) were randomly assigned to two groups. After general anesthesia was induced
with 5 mg/kg thiopental sodium and manual occlusion of venous outflow was
performed, one group of patients received 0.1 mL/kg 1% lidocaine i.v.. A second
group received 0.1 mL/kg of isotonic sodium chloride solution as a placebo
control. Venous outflow occlusion was held for 15 s, released, and immediately
followed by the administration of rocuronium 1 mg/kg i.v.. The patient's response
to rocuronium injection was graded using a 4-point scale. We observed that the
incidence of withdrawal was 84% in the placebo group and was significantly
decreased to 46% in patients pretreated with lidocaine (P < 0.001). This study
demonstrates that the i.v. injection of rocuronium is commonly associated with a
withdrawal reaction in anesthetized pediatric patients and that this reaction can
be attenuated or eliminated by pretreatment with i.v. lidocaine. IMPLICATIONS:
Pain on injection of rocuronium in pediatric patients can be alleviated by
pretreatment with i.v. lidocaine.
PMID- 10195517
TI - Preoperative oral dextromethorphan does not reduce pain or analgesic consumption
in children after adenotonsillectomy.
AB - In this randomized, double-blinded, placebo-controlled, prospective study, we
evaluated the analgesic efficacy of dextromethorphan 0.5 mg/kg or 1.0 mg/kg p.o.
1 h before adenotonsillectomy in 57 children 6-12 yr of age. Anesthetic
management was standardized. Morphine 0.075 mg/kg i.v. and acetaminophen 25-35
mg/kg p.r. were administered after anesthetic induction but before the start of
surgery. A 4-point behavioral score (1 = asleep, 2 = awake and calm, 3 = awake
and crying, 4 = thrashing) was recorded on admission to and discharge from the
postanesthesia care unit (PACU). In the PACU, pain was assessed with Children's
Hospital of Eastern Ontario Pain Scale (CHEOPS) and recorded every 15 min until
the patient was transferred to the day surgery unit (DSU). In the DSU, patients
rated their pain using a 10-cm baseline 0-10 visual analog pain scale (VAS) every
30 min until they were discharged home. A 24-h VAS was obtained by phone
interview, and parental satisfaction was scored (yes/no) regarding their child's
postoperative analgesia. Morphine 0.025 mg/kg i.v. was administered to children
with CHEOPS score >6, who verbalized pain, or who were crying in any consecutive
5-min observation periods in the PACU. Total morphine consumption was recorded.
The study groups were comparable with respect to demographic variables. We were
unable to detect any differences between study groups with respect to
postoperative morphine consumption, CHEOPS, behavior scores, VAS, or parental
satisfaction. IMPLICATIONS: Premedication with dextromethorphan 0.5 or 1.0 mg/kg
p.o. does not improve postoperative analgesia in school-aged children who receive
preemptive morphine 0.075 mg/kg i.v. and acetaminophen 25-35 mg/kg p.r. during
nitrous oxide and desflurane anesthesia for adenotonsillectomy.
PMID- 10195519
TI - The effect of a right-to-left intracardiac shunt on the rate of rise of arterial
and end-tidal halothane in children.
AB - In this prospective study, we evaluated the effect of a right-to-left
intracardiac shunt on the rate of rise of end-tidal and arterial halothane
concentration in children. Six children aged 23-43 mo undergoing surgical closure
of atrial fenestration after Fontan procedure were given 0.8% inspired halothane.
End-tidal halothane was recorded at 1-min intervals after the introduction of
halothane. Arterial halothane concentrations were determined 0, 1, 3, 5, 10, and
15 min after the introduction of halothane. The sampling was performed before and
after closure of the atrial fenestration. The ratio of pulmonary to systemic
blood flow (Qp/Qs) increased in this patient population, from 0.58 +/- 0.04 to
0.88 +/- 0.12 (P = 0.01). The rate of rise of end-tidal halothane did not change
significantly with a decrease in the magnitude of the right-to-left intracardiac
shunt after closure of the atrial fenestration. The ratio of arterial to inspired
halothane concentrations at 1, 3, 5, 10, and 15 min were lower before closure of
the atrial fenestration compared with after closure (P < 0.05). We conclude that
the presence of a right-to-left intracardiac shunt significantly slows the rate
of rise of arterial halothane in the face of a constant inspired concentration.
The rate of rise of end-tidal halothane is not significantly affected in the
presence of a right-to-left intracardiac shunt. IMPLICATIONS: In this prospective
study, we found a slower rate of rise of halothane in arterial blood in children
with right-to-left intracardiac shunting. Induction of anesthesia by inhalation
of volatile anesthetics may therefore be slower in these children.
PMID- 10195518
TI - Evaluating T-wave amplitude as a guide for detecting intravascular injection of a
test dose in anesthetized children.
AB - Previous reports have suggested that accidental intravascular injection of an
epinephrine-containing test dose increases T-wave amplitude in anesthetized
children. We designed this study to prospectively determine whether changes in T
wave amplitude could be a reliable indicator for detecting intravascular
injection. We studied 32 ASA physical status I infants and children (3.4 +/- 1.7
yr) undergoing elective minor surgeries during 1.0 minimum alveolar anesthetic
concentration of sevoflurane and 67% nitrous oxide in oxygen. After the i.v.
administration of atropine 0.01 mg/kg, the patients were randomly assigned to
receive either saline (n = 16) or a test dose consisting of 1% lidocaine (0.1
mL/kg) with 1:200,000 epinephrine (0.5 microg/kg, n = 16) via a peripheral vein
to simulate the intravascular injection of the test dose. Heart rate (HR) and
systolic blood pressure (SBP) were recorded every 20 and 30 s, respectively, and
the T-wave amplitude of lead II was continuously recorded for subsequent
analysis. Of the 16 children receiving the test dose, 16, 13, and 16 developed
increases in HR, SBP, and T-wave amplitude > or = 10 bpm, > or = 15 mm Hg, and >
or = 25%, occurring at 30 +/- 7, 70 +/- 31, and 20 +/- 5 s, respectively. Because
no patient receiving saline met these criteria, sensitivity, specificity, and
positive and negative predictive values were all 100% based on the criteria using
the T-wave amplitude and the peak HR. Our results suggest that changes in T-wave
amplitude are as effective as HR for detecting the intravascular injection of an
epinephrine-containing test dose in sevoflurane-anesthetized children.
IMPLICATIONS: To determine whether an epidurally administered local anesthetic is
unintentionally injected into a blood vessel, a small dose of epinephrine is
often added to a local anesthetic. We found that increases in T-wave amplitude by
> or = 25% in lead II monitor electrocardiography are as effective as a heart
rate increase > or = 10 bpm for detecting intravascular injection in sevoflurane
anesthetized children.
PMID- 10195520
TI - Intraoperative autotransfusion in small children: an in vitro investigation to
study its feasibility.
PMID- 10195521
TI - The assessment of four different methods to verify tracheal tube placement in the
critical care setting.
AB - One of the most serious complications of conventional endotracheal intubation is
unidentified placement of the tube in the esophagus. The aim of our study was to
evaluate four different methods for immediate detection of the tube position:
auscultation, capnographic determination of ETCO2, esophageal detection method
(EDM) using a self-inflating bulb, and the transillumination method using a
lighted stylet (Trachlight; Laerdal, Armonk, NY). Thirty-eight endotracheally
intubated patients admitted to our medical intensive care unit were enrolled in
the study. A second identical tube was inserted into the esophagus under
laryngoscopic control. The endotracheal tube was then disconnected from the
ventilator. Two blinded examiners, one experienced, the other inexperienced,
determined the tube position within 30 s using one of the four methods. The order
of the tubes tested and the methods used were randomized. In 130 of 152
examinations, both examiners correctly diagnosed the position of the tube. The
wrong result was obtained by both examiners 4 times; only the experienced
examiner was wrong 4 times, and only the inexperienced examiner was wrong 14
times. Using ETCO2, both examiners were correct in all cases. Auscultation showed
an obvious relation to the examiner's experience: the experienced examiner was
correct in all cases, the inexperienced examiner was correct in only 68% of
cases. Using the self-inflating bulb, there were two wrong results of the
experienced examiner and one wrong result of the inexperienced examiner. The
transillumination technique was associated with a high error rate by both
examiners (16% and 13%, respectively). Comparing all four methods showed that
capnography is superior to auscultation (P = 0.0005) and to the Trachlight
detection method (P = 0.0078). EDM was not statistically superior to auscultation
and transillumination. Capnography was the most reliable method for rapid
evaluation of tube position, followed by EDM, whereas auscultation and Trachlight
did not seem to be of comparable value. Experience was a determining factor for
auscultation. IMPLICATIONS: To prevent unidentified esophageal intubation, a
serious complication in the critical care setting, four methods for detecting
tube position were tested by two examiners (one experienced, the other
inexperienced) in endotracheally intubated patients after insertion of a second
tube into the esophagus.
PMID- 10195522
TI - Prevention by methylprednisolone of increased circulating tumor necrosis factor
alpha levels and lung injury associated with systemic inflammatory response
syndrome due to intraperitoneal hyperthermia.
AB - We previously demonstrated that intraperitoneal hyperthermic perfusion (IPHP),
which is performed clinically as a treatment for patients with advanced
gastrointestinal cancer, can lead to increased serum tumor necrosis factor-alpha
(TNF-alpha), systemic inflammatory response syndrome (SIRS), and acute lung
injury. Glucocorticoids inhibit the production and actions of TNF-alpha. We
investigated whether pretreatment with methylprednisolone (MPS) may modulate
serum TNF-alpha and lung injury in patients subjected to IPHP. Serum TNF-alpha
was not detected in the patients pretreated with MPS, whereas serum TNF-alpha
increased in the control patients (45.7 +/- 8.3 pg/mL, mean +/- SEM) after IPHP.
Postoperative lung injury scores were significantly lower in patients pretreated
with MPS than in the control patients (P < 0.001). IMPLICATIONS: Pretreatment
with methylprednisolone attenuates the increase in circulating tumor necrosis
factor-alpha and prevents lung injury in this systemic inflammatory syndrome due
to intraperitoneal hyperthermic perfusion.
PMID- 10195523
TI - Tracheo-innominate artery fistula after tracheostomy.
PMID- 10195525
TI - Effects of isoflurane, ketamine, and fentanyl/N2O on concentrations of brain and
plasma catecholamines during near-complete cerebral ischemia in the rat.
AB - We postulated that adrenergic responses to global cerebral ischemia are
anesthetic-dependent and similar in both brain and arterial blood. Rats were
anesthetized with isoflurane (1.4%), ketamine (1 mg x kg(-1) x min(-1)), or
fentanyl (25 microg x kg(-1) x h(-1))/70% N2O. The carotid arteries were occluded
for either 20 min with mean arterial pressure (MAP) 50 mm Hg (incomplete
ischemia) or 10 min with MAP 30 mm Hg (near-complete ischemia). Norepinephrine
was measured in hippocampal microdialysate. Norepinephrine and epinephrine were
measured in arterial plasma. In both hippocampus and plasma, basal norepinephrine
was similar among anesthetics. During incomplete ischemia, hippocampal
norepinephrine was twofold greater with fentanyl/N2O than with isoflurane (P =
0.037), but plasma norepinephrine and epinephrine were similar and unchanged
among all three anesthetics. During near-complete ischemia, hippocampal
norepinephrine was threefold greater with ketamine than fentanyl/N2O (P = 0.005),
whereas plasma norepinephrine and epinephrine were markedly greater with
fentanyl/N2O than with ketamine (P < 0.0005) or isoflurane (P = 0.05). There was
no correlation between norepinephrine concentrations in hippocampus and plasma
for either incomplete or near-complete ischemia. This study demonstrates that
adrenergic responses to global ischemia are anesthetic-dependent, particularly
during more severe insults. The absence of a correlation between plasma and brain
catecholamine concentrations indicates that adrenergic responses to ischemia are
independent in brain and blood. IMPLICATIONS: It has been proposed that
anesthetics modulate cerebral ischemic outcome by influencing peripheral
adrenergic responses to ischemia. This experiment demonstrates that anesthetics
differentially modulate adrenergic responses to ischemia but that effects in
plasma and brain are independent. This suggests that events detected in the
peripheral circulation do not implicate direct mechanisms of action of
catecholamines at the neuronal/glial level.
PMID- 10195526
TI - Venous air embolism during Parkinson surgery in patients with spontaneous
ventilation.
PMID- 10195524
TI - Trabecular outflow facility and formation rate of aqueous humor during anesthesia
with sevoflurane-nitrous oxide or sevoflurane-remifentanil in rabbits.
AB - In the present study, we examined the effect of sevoflurane and remifentanil on
intraocular pressure (IOP) and fluid dynamics. Twenty-eight rabbits were
anesthetized with halothane, and IOP was measured via a 25-gauge needle in the
anterior chamber. Rabbits were then assigned to one of four groups, and halothane
was replaced with sevoflurane 1% (n = 7), 2% (n = 7), 3% (n = 7), or 1% +
remifentanil 0.65 microg kg(-1) x min(-1) i.v. (n = 7). In all groups, a series
of intraocular infusions was made into the anterior chamber, and IOP, trabecular
outflow facility, the rate of aqueous humor formation, and intraocular compliance
were determined. With sevoflurane only, intraocular compliance decreased (55 +/-
14, 39 +/- 22, 31 +/- 17 nL/mm Hg; P < 0.05) as the concentration of sevoflurane
increased. With sevoflurane 1% + remifentanil, intraocular compliance was
significantly increased (100.1 +/- 30.5 nL/mm Hg; P < 0.05) compared with
sevoflurane 1%, 2%, or 3%. Trabecular outflow facility, rate of aqueous humor
formation, and IOP did not differ among groups, and IOP was similar to values
obtained during halothane anesthesia. IMPLICATIONS: The dose-related effects of
sevoflurane on intraocular compliance did not produce significant intraocular
pressure differences. Adding remifentanil to sevoflurane increased intraocular
compliance. Sevoflurane or sevoflurane + remifentanil causes a decrease in
intraocular pressure compared with the average of previously reported values in
awake rabbits, and the magnitude of the decrease is similar to that previously
reported in rabbits anesthetized with ethyl urethane, pentobarbital, or halothane
alone or in combination with propofol, cocaine, or lidocaine.
PMID- 10195527
TI - Panic attacks and lactated Ringer's solution: is there a relationship?
PMID- 10195528
TI - The neurotoxicity of drugs given intrathecally (spinal)
AB - Overall, most spinal drugs in clinical use have been poorly studied for spinal
cord and nerve root toxicity. Laboratory studies indicate that all local
anesthetics are neurotoxic in high concentrations and that lidocaine and
tetracaine have neurotoxic potential in clinically used concentrations. However,
spinal anesthesia (including lidocaine and tetracaine) has a long and enviable
history of safety. Spinal analgesics such as morphine, fentanyl, sufentanil,
clonidine, and neostigmine seem to have a low potential for neurotoxicity based
on laboratory and extensive clinical use. Most antioxidants, preservatives, and
excipients used in commercial formulations seem to have a low potential for
neurotoxicity. In addition to summarizing current information, we hope that this
review stimulates future research on spinal drugs to follow a systematic approach
to determining potential neurotoxicity. Such an approach would examine
histologic, physiologic, and behavioral testing in several species, followed by
cautious histologic, physiologic, and clinical testing in human volunteers and
patients with terminal cancer refractory to conventional therapy.
PMID- 10195529
TI - The epidural "top-up" in combined spinal-epidural anesthesia: the effect of
volume versus dose.
AB - The reinforcement of anesthesia by an epidural "top-up" in combined spinal
epidural anesthesia may be explained by a dual mechanism: a volume effect
compressing the dural sac and a local anesthetic effect. The purpose of our study
was to investigate the relative importance of each of these factors. Fifty
patients scheduled for lower limb orthopedic surgery under combined spinal
epidural anesthesia were randomly allocated to one of five groups comprising 10
patients each. Using a needle-through-needle technique, all patients received a
subarachnoid injection of 10 mg of plain bupivacaine and an epidural catheter.
After the maximal level of sensory blockade as a result of the subarachnoid
injection had been established, an epidural top-up was given according to the
randomization code. Patients in Group 1 received 10 mL of bupivacaine 0.25%;
patients in Group 2 received 10 mL of saline; patients in Group 3 received 5 mL
of bupivacaine 0.5%; patients in Group 4 received 5 mL of saline; and patients in
Group 5 received no epidural top-up. The maximal level of sensory blockade was
then assessed for an additional 30 min. In Groups 1-4, the maximal level of
sensory blockade increased significantly, whereas there was no significant
increase in Group 5. There was no significant difference in the increase in the
maximal level of sensory blockade among Groups 1-4. We conclude that, under the
conditions of our study, there is no difference between 5 and 10 mL with regard
to the volume effect of an epidural top-up in combined spinal-epidural anesthesia
and that to produce an additional local anesthetic effect with bupivacaine, the
dose must be larger than 25 mg. IMPLICATIONS: In combined spinal-epidural
anesthesia, an epidural "top-up" may increase the maximal level of sensory
blockade by means of a volume effect and a local anesthetic effect. In this
study, volumes of 5 and 10 mL produced a similar increase, and 25 mg of
bupivacaine was insufficient to produce an additional local anesthetic effect.
PMID- 10195530
TI - Sameridine is safe and effective for spinal anesthesia: a comparative dose
ranging study with lidocaine for inguinal hernia repair.
AB - Sameridine is a new compound with local anesthetic and analgesic properties when
injected intrathecally. We studied the anesthetic and analgesic efficacy of three
doses of isobaric sameridine (15, 20, and 23 mg) compared with 100 mg of
hyperbaric lidocaine for spinal anesthesia in 140 healthy male patients
undergoing inguinal hernia repair. Patients received spinal anesthesia with 4 mL
of the study drug injected at the L2-3 or L3-4 interspace in the lateral
decubitus position. All three doses of sameridine provided spinal anesthesia
similar to lidocaine, with a slightly longer time to reach peak block height. The
failure rate was highest in the 15-mg sameridine group, and accrual was
discontinued in that group after 35 patients. The duration of blockade was
shorter with lidocaine, but the time to voiding and ambulation was similar in all
groups. Patients receiving sameridine were less likely to request morphine for
postoperative analgesia and were less likely to request any analgesia in the
first 4 h after injection of the drug. Use of oral analgesics (hydrocodone and
acetaminophen) was similar in all groups after the first 4 h of the 24-h
observation. We conclude that, in the three doses studied, sameridine provided
spinal anesthesia similar to lidocaine, but with residual analgesia after drug
injection that reduced the need for systemic analgesics in the first 4 h
postoperatively. IMPLICATIONS: In this clinical trial, we show the potential
efficacy of a class of drugs that can produce both spinal anesthesia and
postoperative analgesia when used for hernia repair.
PMID- 10195531
TI - Optimization of the dose of intrathecal morphine in total hip surgery: a dose
finding study.
AB - We designed this study to determine the optimal intrathecal dose of morphine in
total hip surgery. The optimal intrathecal dose was defined as that providing
effective analgesia and minimal side effects 24 h after total hip surgery.
Patients (n = 143) scheduled for total hip surgery were randomized to four double
blinded groups with a standardized bupivacaine dose but different doses of
intrathecal morphine (Group I = 0.025 mg, Group II = 0.05 mg, Group III = 0.1 mg,
and Group IV = 0.2 mg). Pain scores, i.v. morphine intake (patient-controlled
analgesia), and morphine-related side effects (respiratory depression,
postoperative nausea and vomiting, itching, urinary retention) were recorded for
24 h after surgery. Excellent postoperative pain relief was present in all
groups. The highest pain scores were found in Group I. The mean use of systemic
morphine administered by patient-controlled analgesia infusion pump was 23.7,
17.8, 10.9, and 9.9 mg in Groups I-IV, respectively (P < 0.01 for Groups III and
IV versus Group I). We conclude that 0.1 mg of intrathecal morphine is the
optimal dose for pain relief after hip surgery with minimal side effects.
IMPLICATIONS: Earlier studies showed excellent postoperative pain relief after
intrathecal morphine. However, the severity of side effects resulted in decreased
enthusiasm for this anesthesia technique. In the present study, we show that an
intrathecal dose of 0.1 mg of morphine can be used safely in total hip surgery
with excellent postoperative pain relief.
PMID- 10195532
TI - The effects of three graded doses of meperidine for spinal anesthesia in African
men.
AB - The intrathecal injection of 0.7-1 mg/kg meperidine provides spinal anesthesia of
only short duration. In this study, we investigated the effects of three
different doses of meperidine for spinal anesthesia on the duration and level of
sensory block and the incidence of side effects. Forty-five African men were
randomly allocated to receive one of three doses of intrathecal meperidine: Group
A = 1.2 mg/kg, Group B = 1.5 mg/kg, and Group C = 1.8 mg/kg. The duration of
sensory block was significantly longer after 1.5 mg/kg compared with 1.2 mg/kg
meperidine (112 +/- 19 vs 79 +/- 27 min; P = 0.001). Increasing the dose to 1.8
mg/kg did not further increase the duration of block. The level and the onset of
the block were not affected by the dose. Common side effects were fatigue (27%),
pruritus (20%), and nausea (7%). Seven patients had respiratory depression and
seven had a decrease of systolic arterial blood pressure (SAP) >30% from
baseline. There was no difference in the incidence of any side effect among
groups. Respiratory depression and decreases in SAP were observed 5-50 min after
meperidine injection. Twenty-two patients had no pain after the sensory block had
terminated. We conclude that increasing the dose of meperidine from 1.2 to 1.5
mg/kg increased the duration, but not the level, of sensory block without an
increase in side effects. IMPLICATIONS: Intrathecal meperidine 1 mg/kg provides
surgical anesthesia for only 40-90 min. We investigated the effects of three
larger doses of meperidine in 45 African men. The 1.5 and 1.8 mg/kg doses provide
a longer duration of anesthesia compared with 1.2 mg/kg. Nausea, pruritus, and
respiratory depression were common in all dose groups. We conclude that
increasing the dose of meperidine from 1.2 to 1.5 mg/kg increased the duration,
but not the level, of sensory block without an increase in side effects.
PMID- 10195533
TI - A dose-response study of intravenous regional anesthesia with meperidine.
AB - Intravenous regional anesthesia (IVRA) with meperidine in doses > or = 100 mg
provides effective postoperative analgesia. However, this technique is associated
with excessive opioid-related side effects, which limit its clinical usefulness.
The minimal dose of meperidine that is effective for IVRA has yet to be
established. We added 0, 10, 20, 30, 40, or 50 mg of meperidine to 0.5% lidocaine
IVRA for either carpal tunnel or tenolysis surgery. Pain and sedation scores and
the incidence of side effects were assessed in the postanesthesia care unit. The
duration of analgesia, defined as the time to first request for pain medications,
and use of acetaminophen/codeine (T3) tablets were measured. The duration of
analgesia increased, in a dose-dependent manner, in the groups that received 0,
10, 20, and 30 mg of meperidine. There was no significant difference in the
duration of analgesia for patients receiving > or = 30 mg of meperidine. T3 use
was similar in the groups that received 0, 10, and 20 mg of meperidine and in the
groups that received 30, 40, and 50 mg. T3 use was significantly lower in the
larger dose groups. The incidence of sedation and of all other side effects was
significantly higher in the groups that received 30-50 mg of meperidine compared
with those that received smaller doses. We conclude that doses of meperidine
large enough to produce the most effective postoperative analgesia with IVRA
lidocaine causes a significant incidence of side effects, thus limiting its
clinical usefulness. IMPLICATIONS: Meperidine may be a useful addition to 0.5%
lidocaine for i.v. regional anesthesia. We showed that 30 mg is the optimal dose
of meperidine with respect to postoperative analgesia. However, this dose caused
a significant incidence of sedation, dizziness, and postoperative nausea and
vomiting.
PMID- 10195534
TI - Suppression of pain sensation caused by millimeter waves: a double-blinded, cross
over, prospective human volunteer study.
AB - We conducted a double-blinded, randomized, cross-over, prospective trial to
evaluate the pain relief effect of millimeter waves (MW) under experimental
conditions. The cold pressor test was used as a model of tonic aching pain.
Twelve healthy male volunteers were exposed to an active medical MW generator and
to a disabled sham generator with at least 24 h between exposures.
Characteristics of continuous-wave electromagnetic output from the active
generator were: wavelength 7.1 mm, incident power density 25 +/- 5 mW/cm2, and
duration of exposure 30 min. MW produced a significant (P < 0.05) suppression of
pain sensation, with an average 37.7% gain in pain tolerance and a 49.3% increase
in pain sensitivity range (the latter being the difference between pain tolerance
and pain threshold values). Of the 12 volunteers, 7 (58.3%) reacted to the active
MW generator with an increased pain tolerance, and the individual reactions
varied from 120% to 315% comparison with their own preexposure levels. MW therapy
can potentially be used as a supplementary or alternative treatment for pain
relief. IMPLICATIONS: Pain management is still a significant medical problem. In
a double-blinded, experimental setting, we confirmed that low-intensity
millimeter wave therapy can reduce pain sensitivity in healthy human volunteers
and can potentially be used as a supplementary or alternative treatment for pain
relief.
PMID- 10195535
TI - The effect of stimulus frequency on the analgesic response to percutaneous
electrical nerve stimulation in patients with chronic low back pain.
AB - Low back pain (LBP) is one of the most common medical problems in our society.
Increasingly, patients are turning to nonpharmacologic analgesic therapies such
as percutaneous electrical nerve stimulation (PENS). We designed this sham
controlled study to compare the effect of three different frequencies of
electrical stimulation on the analgesic response to PENS therapy. Sixty-eight
consenting patients with LBP secondary to degenerative lumbar disc disease were
treated with PENS therapy at 4 Hz, alternating 15 Hz and 30 Hz (15/30 Hz), and
100 Hz, as well as sham-PENS (0 Hz), according to a randomized, cross-over study
design. Each treatment was administered for a period of 30 min three times per
week for 2 wk. The pre- and posttreatment assessments included the health status
survey short form and visual analog scales for pain, physical activity, and
quality of sleep. After receiving all four treatments, patients completed a
global assessment questionnaire. The sham-PENS treatments failed to produce
changes in the degree of pain, physical activity, sleep quality, or daily intake
of oral analgesic medications. In contrast, 4-Hz, 15/30-Hz, and 100-Hz
stimulation all produced significant decreases in the severity of pain, increases
in physical activity, improvements in the quality of sleep, and decreases in oral
analgesic requirements (P < 0.01). Of the three frequencies, 15/30 Hz was the
most effective in decreasing pain, increasing physical activity, and improving
the quality of sleep (P < 0.05). In the global assessment, 40% of the patients
reported that 15/30 Hz was the most desirable therapy, and it was also more
effective in improving the patient's sense of well-being. We conclude that the
frequency of electrical stimulation is an important determinant of the analgesic
response to PENS therapy. Alternating stimulation at 15-Hz and 30-Hz frequencies
was more effective than either 4 Hz or 100 Hz in improving outcome measures in
patients with LBP. IMPLICATIONS: The frequency of electrical stimulation seems to
be an important determinant of the analgesic efficacy of percutaneous electrical
nerve stimulation. Mixed low- and high-frequency stimulation was more effective
than either low or high frequencies alone in the treatment of patients with low
back pain.
PMID- 10195536
TI - Nerve stimulator and multiple injection technique for upper and lower limb
blockade: failure rate, patient acceptance, and neurologic complications. Study
Group on Regional Anesthesia.
AB - To evaluate the failure rate, patient acceptance, effective volumes of local
anesthetic solution, and incidence of neurologic complications after peripheral
nerve block performed using the multiple injection technique with a nerve
stimulator, we prospectively studied 3996 patients undergoing combined sciatic
femoral nerve block (n = 2175), axillary blocks (n = 1650), and interscalene
blocks (n = 171). The success rate and mean injected volumes of local anesthetic
were: 93% with 22.6 +/- 4.5 mL in the axillary, 94% with 24.5 +/- 5.4 mL in the
interscalene, and 93% with 28.1 +/- 4.4 mL in the sciatic-femoral nerve blocks.
Patients receiving combined sciatic-femoral nerve block showed more discomfort
during block placement and worse acceptance of the anesthetic procedure than
patients receiving brachial plexus anesthesia. During the first month after
surgery, 69 patients (1.7%) developed neurologic dysfunction on the operated
limb. Complete recovery required 4-12 wk in all patients but one, who required 25
wk. The only variable showing significant association with the development of
postoperative neurologic dysfunction was the tourniquet inflation pressure (<400
mm Hg compared with >400 mm Hg, odds ratio 2.9, 95% confidence intervals 1.6-5.4;
P < 0.001). We conclude that using the multiple injections technique with a nerve
stimulator results in a success rate of >90% with a volume of <30 mL of local
anesthetic solution and an incidence of transient neurologic complication of <2%.
IMPLICATIONS: Based on a prospective evaluation of 3996 consecutive peripheral
nerve blocks, the multiple injection technique with nerve stimulator allows for
up to 94% successful nerve block with <30 mL of local anesthetic solution.
Although the data collection regarding neurologic dysfunction was limited, the
withdrawal and redirection of the stimulating needle was not associated with an
increased incidence of neurologic complications. Sedation/analgesia should be
advocated during block placement to improve patient acceptance.
PMID- 10195537
TI - Tramadol added to mepivacaine prolongs the duration of an axillary brachial
plexus blockade.
AB - Tramadol is an analgesic drug that is antagonized by alpha2-adrenoceptor
antagonists, as well as opioid antagonists. We hypothesized that tramadol might
produce effects on an axillary brachial plexus blockade similar to those of
clonidine. We designed a prospective, controlled, double-blinded study to assess
the impact of tramadol added to mepivacaine on the duration of an axillary
brachial plexus blockade. After institutional approval and informed consent, 60
patients (ASA physical status I or II) scheduled for forearm and hand surgery
after trauma under brachial plexus anesthesia were included in the study.
Patients were randomly assigned to receive either 40 mL of mepivacaine 1% with 2
mL of isotonic sodium chloride solution (Group A, n = 20); 40 mL of mepivacaine
1% with 100 mg of tramadol (Group B, n = 20); or 40 mL of mepivacaine 1% with 2
mL of isotonic sodium chloride solution and 100 mg of tramadol i.v. (Group C, n =
20). Sensory block, motor block, and hemodynamics were recorded before and 5, 10,
30, 60, 120, 180, and 360 min after local anesthetic injection. Duration of
sensory and motor block was significantly longer (P < 0.01; P < 0.05) in Group B
(299 +/- 84 and 259 +/- 76 min) than in Group A (194 +/- 35 and 181 +/- 24 min)
and Group C (187 +/- 35 and 179 +/- 16 min). There was no difference in onset of
sensory and motor blockade among groups. Hemodynamics remained unchanged in all
patients throughout the study period. We conclude that the addition of tramadol
prolongs the duration of brachial plexus block without side effects. Tramadol may
be an alternative to epinephrine or clonidine as an adjuvant to local anesthesia
for an axillary block. IMPLICATIONS: This study demonstrates that the admixture
of 100 mg of tramadol with mepivacaine 1% for brachial plexus block provides a
pronounced prolongation of blockade without side effects. Our data support a
specific analgesic effect of tramadol on peripheral nerves.
PMID- 10195539
TI - Endoscopic thoracic sympathectomy for primary erythromelalgia in the upper
extremities.
PMID- 10195538
TI - A comparison of epidural ropivacaine infusion alone and in combination with 1, 2,
and 4 microg/mL fentanyl for seventy-two hours of postoperative analgesia after
major abdominal surgery.
AB - Our aim in this prospective, randomized, double-blinded study was to compare the
analgesic effectiveness and side effects of epidural infusions with ropivacaine 2
mg/mL alone (Group R; n = 60) and in combination with fentanyl 1 microg/mL (R1F;
n = 59), 2 microg/mL (R2F; n = 62), and 4 microg/mL (R4F; n = 63) for up to 72 h
after major abdominal surgery. Effective epidural neural blockade was established
before surgery; postoperatively, the infusion rate was titrated to a maximum of
14 mL/h for analgesia. No additional analgesics other than acetaminophen were
permitted during the infusion. The median of individual visual analog scale score
with coughing were <20 mm for all groups (0 = no pain, 100 = worst pain) and was
significantly lower (P < 0.01) for Group R4F at rest and with coughing (compared
with Group R). Infusions were discontinued due to inability to control pain in
significantly fewer patients in Group R4F (16%) than the other groups (34% to
39%; P < 0.01). For all groups, >90% of patients had no detectable motor block
after 24 h. Hypotension, nausea, and pruritus were more common with the larger
dose of fentanyl. We conclude that, after major abdominal surgery, an epidural
infusion of ropivacaine 2 mg/mL with fentanyl 4 microg/mL provided significantly
more effective pain relief over a 3-day period than ropivacaine alone or
ropivacaine with lower concentrations of fentanyl. IMPLICATIONS: Postoperative
epidural analgesic infusions are widely used, but there is little information
regarding optimal strengths of opioid with local anesthetic. In this blinded,
prospective study, we compared four different epidural infusion solutions for
efficacy and side effects over a clinically useful postoperative period and
conclude that an epidural infusion of ropivacaine 2 mg/mL with fentanyl 4
microg/mL was most effective.
PMID- 10195540
TI - Minimum alveolar anesthetic concentration of fluorinated alkanols in rats:
relevance to theories of narcosis.
AB - The Meyer-Overton hypothesis predicts that the potency of conventional inhaled
anesthetics correlates inversely with lipophilicity: minimum alveolar anesthetic
concentration (MAC) x the olive oil/gas partition coefficient equals a constant
of approximately 1.82 +/- 0.56 atm (mean +/- SD), whereas MAC x the octanol/gas
partition coefficient equals a constant of approximately 2.55 +/- 0.65 atm. MAC
is the minimum alveolar concentration of anesthetic required to eliminate
movement in response to a noxious stimulus in 50% of subjects. Although MAC x the
olive oil/gas partition coefficient also equals a constant for normal alkanols
from methanol through octanol, the constant (0.156 +/- 0.072 atm) is one-tenth
that found for conventional anesthetics, whereas the product for MAC x the
octanol/gas partition coefficient (1.72 +/- 1.19) is similar to that for
conventional anesthetics. These normal alkanols also have much greater affinities
for water (saline/gas partition coefficients equaling 708 [octanol] to 3780
[methanol]) than do conventional anesthetics. In the present study, we examined
whether fluorination lowers alkanol saline/gas partition coefficients (i.e.,
decreases polarity) while sustaining or increasing lipid/gas partition
coefficients, and whether alkanols with lower saline/gas partition coefficients
had products of MAC x olive oil or octanol/gas partition coefficients that
approached or exceeded those of conventional anesthetics. Fluorination decreased
saline/gas partition coefficients to as low as 0.60 +/- 0.08 (CF3[CF2]6CH2OH)
and, as hypothesized, increased the product of MAC x the olive oil or octanol/gas
partition coefficients to values equaling or exceeding those found for
conventional anesthetics. We conclude that the greater potency of many alkanols
(greater than would be predicted from conventional inhaled anesthetics and the
Meyer-Overton hypothesis) is associated with their greater polarity.
IMPLICATIONS: Inhaled anesthetic potency correlates with lipophilicity, but
potency of common alkanols is greater than their lipophilicity indicates, in part
because alkanols have a greater hydrophilicity--i.e., a greater polarity.
PMID- 10195541
TI - Actions of fluorinated alkanols on GABA(A) receptors: relevance to theories of
narcosis.
AB - Previous work demonstrates that various anesthetics enhance the effect of gamma
aminobutyric acid (GABA), and this enhancement has been proposed as an
explanation for how anesthetics cause anesthesia. This explanation extends to
both fluorinated and unfluorinated alkanols. In the present study, we tested the
capacity of fluorinated alkanols to enhance the function of the GABA(A) receptors
expressed in Xenopus oocytes. CF3CH2OH, CF3(CF2)2CH2OH and CF3(CF2)4CH2OH
potentiated GABA(A) receptor function, but CF3(CF2)5CH2OH did not. The degree of
potentiation decreased in proportion to the chain length of the alkanols. These
findings were not specific for receptors expressed in oocytes, as similar results
were obtained with muscimol-stimulated 36Cl- uptake using mouse brain membrane
vesicles. Although CF3(CF2)5CH2OH has been reported to enhance the capacity of
desflurane to produce immobility in vivo, in our in vitro studies, this compound
reduced potentiation of GABA-gated response by anesthetics such as isoflurane,
enflurane, and pentobarbital. CHF2(CF2)5CH2OH, which has in vivo anesthetic
effects, also failed to potentiate GABA(A) receptor function. These results
indicate that the GABA(A) receptor is not the only receptor affected by
fluorinated alkanols and that other receptors contribute to the capacity of
alkanols to produce immobility. In particular, CF3(CF2)5CH2OH and CF3CH2OH
inhibited N-methyl-D-aspartate receptor-mediated responses, which raises the
possibility that this receptor is important for actions of fluorinated alkanols.
IMPLICATIONS: We find a consistent parallel between the immobilization produced
by fluorinated alkanols and their actions on N-methyl-D-aspartate receptors but
do not find a consistent parallel between immobilization and effects on gamma
aminobutyric acid type A receptors. Thus, we suggest that N-methyl-D-aspartate,
but not gamma-aminobutyric acid type A, receptors may mediate the capacity of
anesthetics to produce immobilization.
PMID- 10195542
TI - Nonimmobilizers and transitional compounds may produce convulsions by two
mechanisms.
AB - Some inhaled compounds cause convulsions. To better appreciate the physical basis
for this property, we correlated the partial pressures that produced convulsions
in rats with the lipophilicity (nonpolarity) and hydrophilicity (polarity) of 45
compounds: 3 n-alkanes, 18 n-haloalkanes, 3 halogenated aromatic compounds, 3
cycloalkanes and 3 halocycloalkanes, 13 halogenated ethers, and 2 noble gases (He
and Ne). In most cases, convulsions were quantified by averaging the alveolar
partial pressures just below the pressures that caused and slightly higher
pressures that did cause clonic convulsions (ED50). The ED50 did not correlate
with hydrophilicity (the saline/gas partition coefficient), nor was there an
obvious correlation with molecular structure. For 80% of compounds (36 of 45),
the ED50 correlated closely (r2 = 0.99) with lipophilicity (the olive oil/gas
partition coefficient). Perhaps because they block the effect of GABA on GABA(A)
receptors, five compounds were more potent than would be predicted from their
lipophilicity. Conversely, four compounds may have been less potent than would be
predicted because they (like conventional inhaled anesthetics) enhance the effect
of GABA on GABA(A) receptors. IMPLICATIONS: Nonimmobilizers and transitional
compounds may produce convulsions by two mechanisms. One correlates with
lipophilicity (nonpolarity), and the other correlates with an action on GABA(A)
receptors.
PMID- 10195543
TI - Xenon has greater inhibitory effects on spinal dorsal horn neurons than nitrous
oxide in spinal cord transected cats.
AB - Xenon (Xe) suppresses wide dynamic range neurons in cat spinal cord to a similar
extent as nitrous oxide (N2O). The antinociceptive action of N2O involves the
descending inhibitory system. To clarify whether the descending inhibitory system
is also involved in the antinociceptive action of Xe, we compared the effects of
Xe on the spinal cord dorsal horn neurons with those of N2O in spinal cord
transected cats anesthetized with alpha-chloralose and urethane. We investigated
the change of wide dynamic range neuron responses to touch and pinch by both
anesthetics. Seventy percent Xe significantly suppressed both touch- and pinch
evoked responses in all 12 neurons. In contrast, 70% N2O did not show significant
suppression in touch- and pinch-evoked responses. These results suggest that the
antinociceptive action of Xe might not be mediated by the descending inhibitory
system, but instead may be produced by the direct effect on spinal dorsal horn
neurons. IMPLICATIONS: Xenon (Xe) is an inert gas with anesthetic properties. We
examined the antinociceptive effects of Xe and nitrous oxide (N2O) in spinal cord
transected cats. Our studies indicate that Xe has a direct antinociceptive action
on the spinal cord that is greater than that of N2O.
PMID- 10195544
TI - Perioperative plasma endothelin-1 and Big endothelin-1 concentrations in elderly
patients undergoing major surgical procedures.
AB - Plasma concentrations of the vasoconstrictor endothelin-1 (ET-1) increase during
acute physiologic stress, but the role of ET-1 in the pathophysiology of stress
remains largely undefined. Whether ET-1 mediates thermoregulatory changes in
vasomotor tone is unknown. ET-1 and its more stable precursor, Big ET-1, were
measured in plasma obtained at several perioperative time points from 95
consecutive elderly patients (mean age 70 +/- 1 yr) randomized to receive either
normothermic or hypothermic perioperative care while undergoing major surgical
procedures. In the postoperative period, there were no significant changes in
plasma ET-1 concentrations, but Big ET-1 concentrations increased considerably (P
< 0.0001). There were no significant differences in mean ET-1 or Big ET-1 levels
in normothermic and hypothermic patients. Preoperative and postoperative ET-1
concentrations were significantly higher in patients with a history of
hypertension (P < 0.002) and in those requiring treatment for postoperative
hypertension (P < 0.003). Patients with cancer and those undergoing abdominal
surgery had significantly higher Big ET-1 concentrations (P < 0.0001 and P <
0.003, respectively). These data support the hypothesis that Big ET-1 is a more
sensitive measure of endothelin system activation after major surgery. Premorbid
conditions and location and type of surgery influence perioperative ET-1/Big ET-1
concentrations. IMPLICATIONS: The endothelin response seems to be significantly
associated with perioperative hemodynamic aberrations. The endothelin-1 (ET-1)
precursor Big ET-1 is a more sensitive measure of the endothelin system
activation in response to surgical stress than ET-1 alone. Thermoregulatory
vasoconstriction in response to mild perioperative hypothermia occurs
independently of the endothelin system.
PMID- 10195545
TI - Do laryngeal mask airway devices attenuate liquid flow between the esophagus and
pharynx? A randomized, controlled cadaver study.
AB - In this randomized, controlled cadaver study, we tested the hypothesis that the
standard laryngeal mask airway (LMA) and flexible laryngeal mask airway (FLMA)
attenuate liquid flow between the esophagus and pharynx. Fifty fresh cadavers
were studied in four LMA groups. Ten female cadavers had a size 4 LMA and 10 had
a size 4 FLMA; 10 male cadavers had a size 5 LMA and 10 had a size 5 FLMA; 5 male
and 5 female cadavers functioned as controls. The chest was opened, and the
infusion set of a pressure-controlled, continuous flow pump was inserted into the
esophagus and ligated into place. Esophageal pressure was increased in 2-cm H2O
increments. Regurgitation pressure was the esophageal pressure at which fluid was
first seen with a fiberoptic scope in the hypopharynx (control group) and above
the cuff or within the bowl (LMA groups). This was performed in the LMA groups at
0-40 mL cuff volume in 10-mL increments. Mean (95% confidence interval)
regurgitation pressure for the control group was 7 (6-8) cm H2O and for the LMA
groups combined was 19 (17-20) cm H2O at 0 mL cuff volume, 47 (41-52) cm H2O at
10 mL, 51 (44-55) cm H2O at 20 mL, 52 (45-56) cm H2O at 30 mL, and 52 (45-55) cm
H2O at 40 mL. The increase in regurgitation pressure with increasing cuff volume
from 0 to 10 mL was statistically significant (P < 0.0001). Regurgitation
pressure was higher for the LMA groups at all cuff volumes compared with the
control group (P < 0.0001). There were no differences in regurgitation pressure
among the LMA groups. We conclude that the correctly placed LMA and FLMA
attenuate liquid flow between the esophagus and pharynx. IMPLICATIONS: We have
shown, in cadavers, that the correctly placed standard and flexible laryngeal
mask airways attenuate liquid flow between the pharynx and esophagus.
PMID- 10195546
TI - Comparison of sevoflurane with propofol for laryngeal mask airway insertion in
adults.
AB - We performed a prospective, randomized, controlled trial to compare the quality
and ease of laryngeal mask airway (LMA) insertion after either rapid inhaled
sevoflurane or i.v. propofol induction of anesthesia. Seventy-six unpremedicated
ASA physical status I or II patients were anesthetized with either a single vital
capacity breath of sevoflurane 8% or i.v. propofol 3 mg/kg, which produced
equally rapid loss of consciousness (40.5 +/- 13.9 vs 37.7 +/- 9.9 s; P > 0.05).
The LMA was inserted more rapidly in patients in the propofol group (74 +/- 29 vs
127 +/- 35 s; P < 0.01) and required fewer attempts (1.2 vs 1.6; P < 0.05) than
the sevoflurane group. There was a greater incidence of initially impossible
mouth opening in the sevoflurane group (45% vs 21%; P < 0.05). Once mouth opening
was possible, the degree of attenuation of laryngeal reflexes was similar. The
overall incidence of complications related to LMA insertion, especially apnea
(32% vs 0%; P < 0.01), was more frequent in the propofol group (82% vs 26%; P <
0.01). There were four failures of LMA insertion in the propofol group and none
in the sevoflurane group. Both groups had stable hemodynamic profiles and good
patient satisfaction. We conclude that sevoflurane vital capacity breath
induction compares favorably with i.v. propofol induction for LMA insertion in
adults. However, prolonged jaw tightness after the sevoflurane induction of
anesthesia may delay LMA insertion. IMPLICATIONS: In this randomized, controlled
trial, we compared the ease of insertion of the laryngeal mask airway in adults
after induction of anesthesia with either a sevoflurane vital capacity breath
technique or propofol i.v.. We conclude that sevoflurane compares favorably with
propofol, although prolonged jaw tightness may delay laryngeal mask airway
insertion.
PMID- 10195547
TI - The influence of head and neck position on oropharyngeal leak pressure and cuff
position with the flexible and the standard laryngeal mask airway.
AB - We conducted a randomized, cross-over study of 20 paralyzed anesthetized adult
patients to test the hypothesis that oropharyngeal leak pressure and cuff
position (assessed fiberoptically) vary with head and neck position for the
flexible (FLMA) and standard laryngeal mask airway (LMA). Both devices were
inserted into each patient in random order. Oropharyngeal leak pressure and
fiberoptic position (including degree of rotation) were documented in four head
and neck positions (neutral first, then flexion, then extension and rotation in
random order) for each device. The size 5 was used for all patients, and the
intracuff pressure was set at 60 cm H2O in the neutral position. All airway
devices were inserted at the first attempt. Oropharyngeal leak pressure was
similar for the FLMA and LMA in the neutral (22 vs 21 cm H2O), flexed (26 vs 26
cm H2O), and extended positions (19 vs 18 cm H2O) but was slightly higher for the
LMA when the head was rotated (19 vs 22 cm H2O; P = 0.04). Compared with the
neutral position, oropharyngeal leak pressure for the LMA was higher with flexion
(26 vs 21 cm H2O; P = 0.0004) and lower with extension (18 vs 21 cm H2O; P =
0.03) but similar with rotation. Compared with the neutral position,
oropharyngeal leak pressure for the FLMA was higher with flexion (26 vs 22 cm
H2O; P = 0.0001) and lower with extension (19 vs 22 cm H2O; P = 0.03) and
rotation (19 vs 22 cm H2O; P = 0.03). The difference in oropharyngeal leak
pressure between flexion and extension was 7 and 8 cm H2O for the FLMA and LMA,
respectively. Fiberoptic position was similar between devices and was unchanged
by head and neck position. Rotation was not detected fiberoptically. We conclude
that there are small changes in oropharyngeal leak pressure but no changes in
cuff position in different head and neck positions for the FLMA and LMA.
Oropharyngeal leak pressure may be improved by head and neck flexion and by
avoiding extension. IMPLICATIONS: There are small changes in oropharyngeal leak
pressure but no changes in cuff position in different head and neck positions for
the flexible and standard laryngeal mask airways. Oropharyngeal leak pressure may
be improved by head and neck flexion and by avoiding extension.
PMID- 10195548
TI - The target plasma concentration of propofol required to place laryngeal mask
versus cuffed oropharyngeal airway.
AB - To determine the target plasma concentration of propofol required to place either
a laryngeal mask airway (LMA) or a cuffed oropharyngeal airway (COPA), we started
a continuous target-controlled infusion of propofol in 60 ASA physical status I
or II unpremedicated patients scheduled for minor orthopedic surgery with
peripheral nerve block. The target plasma concentration of propofol was initially
set at 2 microg/mL. When the effect-site calculated concentration of propofol was
equal to the plasma concentration according to the computer simulation, the
target plasma concentration was increased by 0.5-microg/mL steps until successful
placement of either the LMA (n = 30) or the COPA (n = 30). The mean target plasma
concentration of propofol required to place a LMA was 4.3 +/- 0.8 microg/mL
compared with 3.2 +/- 0.6 microg/mL to place a COPA (P < 0.001). To successfully
place the airways in 95% of patients, the target plasma concentration of propofol
had to be increased up to 4 microg/mL for the COPA and 6 microg/mL for the LMA.
We conclude that placing a LMA in healthy, unpremedicated patients requires
target plasma concentrations of propofol higher than those required for placing a
COPA. IMPLICATIONS: We evaluated the use of target-controlled infusion of
propofol to place extratracheal airways in this prospective, randomized study and
demonstrated that the target plasma concentration of propofol required to
successfully place a laryngeal mask in >95% of healthy, unpremedicated patients
is 6 microg/mL, compared with 4 microg/mL to place a cuffed oropharyngeal airway.
PMID- 10195549
TI - Less core hypothermia when anesthesia is induced with inhaled sevoflurane than
with intravenous propofol.
AB - Hypothermia after the induction of anesthesia results initially from core-to
peripheral redistribution of body heat. Sevoflurane and propofol both inhibit
central thermoregulatory control, thus causing vasodilation. Propofol differs
from sevoflurane in producing substantial peripheral vasodilation. This
vasodilation is likely to facilitate core-to-peripheral redistribution of heat.
Once heat is dissipated from the core, it cannot be recovered. We therefore
tested the hypothesis that the induction of anesthesia with i.v. propofol causes
more core hypothermia than induction with inhaled sevoflurane. We studied
patients undergoing minor oral surgery randomly assigned to anesthetic induction
with either 2.5 mg/kg propofol (n = 10) or inhalation of 5% sevoflurane (n = 10).
Anesthesia in both groups was subsequently maintained with sevoflurane and 60%
nitrous oxide in oxygen. Calf minus toe skin temperature gradients <0 degrees C
were considered indicative of significant vasodilation. Ambient temperature and
end-tidal concentrations of maintenance sevoflurane were comparable in each
group. Patients in both groups were vasodilated throughout most of the surgery.
Nonetheless, core temperatures in patients who received propofol were
significantly lower than those in patients who received inhaled sevoflurane.
These data support our hypothesis that even a brief period of vasodilation causes
substantial redistribution hypothermia that persists throughout surgery.
IMPLICATIONS: Core temperatures in patients who received i.v. propofol were
consistently lower than those in patients who received inhaled sevoflurane,
although anesthesia was subsequently maintained with sevoflurane in nitrous oxide
in both groups. This suggests that even a brief period of propofol-induced
vasodilation during anesthetic induction causes substantial redistribution
hypothermia that persists throughout surgery.
PMID- 10195550
TI - Exposure to sevoflurane and nitrous oxide during four different methods of
anesthetic induction.
AB - The National Institute for Occupational Safety and Health-recommended exposure
levels for nitrous oxide exposure are 25 ppm as a time-weighted average over the
time of exposure. The exposure limit for halogenated anesthetics (without
concomitant nitrous oxide exposure) is 2 ppm. Inhaled sevoflurane provides an
alternative to i.v. induction of anesthesia. However, the inadvertent release of
anesthetic gases into the room is likely to be greater than that with induction
involving i.v. anesthetics. We therefore evaluated anesthesiologist exposure
during four different induction techniques. Eighty patients were assigned to one
of the induction groups to receive: 1) sevoflurane and nitrous oxide from a
rebreathing bag, 2) sevoflurane and nitrous oxide from a circle circuit, 3)
propofol 3 mg/kg, and 4) thiopental sodium 5 mg/kg. Anesthesia was maintained
with sevoflurane and nitrous oxide via a laryngeal mask. Trace concentrations
were measured directly from the breathing zone of the anesthesiologist. During
induction, peak concentrations of sevoflurane and nitrous oxide with the two i.v.
methods rarely exceeded 2 ppm sevoflurane and 50 ppm nitrous oxide.
Concentrations during the two inhalation methods were generally <20 ppm
sevoflurane and 100 ppm nitrous oxide. During maintenance, median values were
near 2 ppm sevoflurane and 50 ppm nitrous oxide in all groups. Sevoflurane
concentrations during inhaled induction frequently exceeded the National
Institute for Occupational Safety and Health-recommended exposure ceiling of 2
ppm but mostly remained <20 ppm. Exposure during the maintenance phase of
anesthesia also frequently exceeded the 2-ppm ceiling. We conclude that operating
room anesthetic vapor concentrations are increased during inhaled inductions and
remain increased with laryngeal mask ventilation. IMPLICATIONS: We compared waste
gas concentrations to sevoflurane and nitrous oxide during four different
induction methods. During inhaled induction with a rebreathing bag or a circle
circuit system, waste gas concentrations frequently exceed National Institute for
Occupational Safety and Health limits of 2 ppm sevoflurane and 50 ppm nitrous
oxide. Therefore, we recommend that people at risk (e.g., women of child-bearing
age) should pay great attention when using this technique.
PMID- 10195552
TI - The effect of lidocaine on bacterial growth in propofol.
AB - Extrinsically contaminated propofol has been associated with multiple infectious
complications. Injection of propofol is associated with pain that is diminished
by the addition of lidocaine. Lidocaine has antibacterial properties at high
concentrations, but low concentrations of lidocaine (0.1%) have not been studied.
We examined the growth rates of Staphylococcus aureus, Serratia marcescens,
Pseudomonas aeruginosa, and Candida albicans in propofol containing disodium
edeteate with and without added lidocaine 0.1% 2, 5, and 24 h after inoculation.
There was no significant difference in the number of colony-forming units between
propofol with and without added lidocaine at any time after inoculation.
IMPLICATIONS: The addition of lidocaine to propofol in concentrations clinically
effective in reducing pain on injection had no effect on microbial growth.
Adherence to strict aseptic technique is further emphasized.
PMID- 10195551
TI - Onset time, recovery duration, and drug cost with four different methods of
inducing general anesthesia.
AB - We compared two conventional induction techniques (thiopental and propofol), an
inhaled induction with sevoflurane using a circle system, and a rebreathing
method. Fentanyl 1 microg/kg was given to women undergoing 10- to 20-min
procedures. Anesthesia was induced (n = 20 each) with one of the following: 1)
sevoflurane and N2O from a rebreathing bag (Sevo/Bag). A 5-L bag was prefilled
with a mixture of sevoflurane 7% and N2O 60% in oxygen. The bag was connected
between the normal circle system, separated by a spring-loaded valve; 2)
sevoflurane 8% and N2O 60% from a circle system on a conventional anesthesia
machine with a total fresh gas flow of 6 L/min (Sevo/Circle); 3) propofol 3 mg/kg
as an i.v. bolus; 4) thiopental sodium 5 mg/kg as an i.v. bolus. Postoperative
nausea and vomiting was treated with ondansetron. Induction times were comparable
with each method. Recovery duration was shortest with sevoflurane, intermediate
with propofol, and longest with thiopental. Induction drug costs were lowest with
Sevo/Bag and thiopental, intermediate with Sevo/Circle, and highest with
propofol. However, sevoflurane (by either method) caused considerable nausea and
vomiting that required treatment. Consequently, total drug cost was least with
thiopental, intermediate with Sevo/Bag and propofol, and greatest with
Sevo/Circle. Thus, no single technique was clearly superior. IMPLICATIONS:
Anesthetic induction techniques influence awakening time, recovery duration, and
drug costs. We tested two i.v. methods and two inhaled techniques. However, none
of the four tested methods was clearly superior to the others.
PMID- 10195553
TI - The effect of tenoxicam on intraperitoneal adhesions and prostaglandin E2 levels
in mice.
AB - We determined whether tenoxicam administered intraperitoneally in the
preoperative period had an effect on the development of postoperative
intraabdominal adhesions (IAA). For this purpose, 100 albino mice were divided
into four random groups. Mice in Group 1 were given only 1 mL of 0.9% NaCl
intraperitoneally, whereas in Group 2, 1 mL of tenoxicam (150 microg = 5 mg/kg)
was administered. After the induction of anesthesia, a median laparotomy was
performed, and the bowels were traumatized by touching them with powdered gloves
before the incision was closed in Groups 3 and 4. Intraperitoneal tenoxicam was
administered to mice in Group 4 after skin closure. All mice were killed after 14
days to determine macroscopic and microscopic IAA; prostaglandin E2 levels were
also measured. Postoperative evaluation revealed a reduced IAA formation and a
parallel decrease in tissue prostaglandin E2 levels in Group 1 and 2 mice. We
conclude that intraperitoneal tenoxicam decreased IAA formation with no
peritoneal reaction in the postoperative period. IMPLICATIONS: Postoperative
intraabdominal adhesions can cause intestinal obstruction, pelvic pain, or
infertility. In this study, we showed that intraperitoneally administered
tenoxicam decreases tissue prostaglandin E2 levels and intraabdominal adhesions
in mice.
PMID- 10195554
TI - The laryngotracheal topical anesthesia kit with capnography for difficult
endotracheal intubation.
PMID- 10195555
TI - Alcohol withdrawal in the surgical patient: prevention and treatment.
AB - In the literature on AWS, there is repeated emphasis on performing a thorough
preanesthesia assessment in patients with suspected chronic alcohol use. Because
these patients are difficult to diagnose and to treat in surgical settings if
complications arise, a multimodal approach is highly recommended (86). Ideally,
AWS should be prevented by adequate prophylaxis. If AWS develops after surgery or
trauma, immediate therapy is required. The symptoms of AWS can be controlled
using the combination of a benzodiazepine (in Europe, also chlormethiazole) with
haloperidol or clonidine. The drug regimens must be individualized and symptom
oriented to treat hallucinations and autonomic signs. Dosages are generally
larger than those in detoxification units. Other approaches to modulate the
neuroendocrine-immune axis in patients with an increased risk of postoperative
infectious complications look promising but await controlled trials.
PMID- 10195556
TI - Twelfth annual meeting of the Society for Pediatric Anesthesia, Orlando, Florida,
October 16, 1998.
PMID- 10195557
TI - Comparison of the laryngeal mask airway and cuffed oropharyngeal airway:
alternative hypotheses.
PMID- 10195558
TI - Epidural opioids and respiratory arrests.
PMID- 10195559
TI - The influence of epidural needle bevel on spread of sensory blockade in the
laboring parturient.
PMID- 10195560
TI - Successful strategies for improving operating room efficiency at academic
institutions.
PMID- 10195561
TI - Epidural analgesia and cesarean delivery: what is the relationship?
PMID- 10195562
TI - Valuing the work performed by anesthesiology residents.
PMID- 10195563
TI - Pacemaker-driven tachycardia revisited.
PMID- 10195564
TI - Saline solution as lubrication to manipulate a stuck fiberoptic bronchoscope.
PMID- 10195565
TI - Perioperative torsade de pointes ventricular tachycardia.
PMID- 10195566
TI - Distinct biological effects of macrophage inflammatory protein-1alpha and stroma
derived factor-1alpha on CD34+ hemopoietic cells.
AB - Chemokines are important regulators of both hemopoietic progenitor cell (HPC)
proliferation and adhesion to extracellular matrix molecules. Here, we compared
the biological effects of the CC chemokine macrophage inflammatory protein-1alpha
(MIP-1alpha) with those of the CXC chemokine stroma-derived factor-1alpha (SDF
1alpha) on immunomagnetically purified CD34+ cells from leukapheresis products
(LP CD34+). In particular, studies on chemokine-induced alterations of LP CD34+
cell attachment to fibronectin-coated plastic surfaces, proliferation of these
cells in colony-forming cell (CFC) assays and intracellular calcium mobilization
were performed. MIP-1alpha but not SDF-1alpha was found to increase the adhesion
of LP CD34+ cells to fibronectin in a dose-dependent manner. Both chemokines
elicited growth-suppressive effects on LP CD34+ cells in CFC assays. While MIP
1alpha reduced the number of granulomonocytic (CFC-GM) and erythroid (BFU-E)
colonies to the same extent, SDF-1alpha showed a significantly greater inhibitory
effect on CFC-GM than BFU-E. Finally, we demonstrated that SDF-1alpha but not MIP
1alpha triggers increases in intracellular calcium in LP CD34+ cells. The SDF
1alpha-induced calcium response was rapid and concentration-dependent, with a
maximal stimulation observed at > or = 15 ng/ml. In conclusion, our data suggest
distinct biological properties of SDF-1alpha and MIP-1alpha in terms of
modulation of LP CD34+ cell adhesion to fibronectin and intracellular calcium
levels. However, comparable growth-suppressive effects on HPC proliferation were
observed, indicating that this feature may be independent of chemokine-induced
calcium responses.
PMID- 10195567
TI - In vitro endothelial differentiation of long-term cultured murine embryonic yolk
sac cells induced by matrigel.
AB - The yolk sac of an early mammalian embryo contains progenitors of hematopoietic
cells and vascular endothelial cells. We established a cell line, YS4, from
murine embryonic yolk sac 10 years ago. The line has been successfully cultured
since then. To determine whether these long-term cultured yolk sac cells still
have the potential to differentiate into endothelial cells, an in vitro model of
yolk sac cell differentiation into tubeforming endothelial cells was established
in the present study by culturing the yolk sac cells on basement membrane
proteins (Matrigel). The results indicate that upon plating onto Matrigel, YS4
cells attach quickly, align in tandem, and form a complete network of capillary
structures within 12 h. By using antibodies against the known components of
Matrigel in a tube formation inhibition assay, we found that extracellular matrix
proteins such as laminin, collagen IV, vitronectin, and fibronectin are the most
important components in the Matrigel which induce the yolk sac cells to undergo
endothelial differentiation. New basement membrane proteins are also required for
the endothelial differentiation process, as indicated by the fact that base
membrane protein synthesis inhibitor, D609, can block the differentiation
process. Furthermore, our experiments revealed the involvement of several signal
transduction pathways, such as protein kinase A, C and protein tyrosine kinase in
this differentiation process.
PMID- 10195568
TI - HGF activates signal transduction from EPO receptor on human cord blood
CD34+/CD45+ cells.
AB - Hepatocyte growth factor (HGF) is a multifunctional cytokine with early
hematopoiesis-stimulatory activity. Here, we focus on its erythropoiesis
stimulatory effect on highly purified human hematopoietic progenitor cells
(CD34+/CD45+ cells) derived from the cord blood. In immunoblot analyses, c-met
protein (a receptor of HGF) was detected in the CD34+/CD45+ cells, although the
expression levels were different among samples. The c-met expression was
facilitated by incubation of the cells with stem cell factor (SCF) or interleukin
3 (IL-3), even if the expression level had been low. IL-6, G-CSF, or
erythropoietin (EPO) did not show such a stimulatory effect on the c-met
expression of the cells. When HGF was added to the CD34+/CD45+ cells in the
presence of SCF, the numbers of CD36+/CD11b- cells (very early erythroid lineage
cells) and BFU-E increased. EPO-dependent tyrosine phosphorylation of Stat 5 also
increased, but the EPO receptor (EPO-R) expression remained unchanged in the
CD34+/CD45+ cells treated with SCF + HGF. Our present study suggests that
stimulation of the HGF/c-met signal is concomitant with induction of c-met
protein by SCF. The subsequent enhancement of signal transduction via the
activation of Stat 5 from the EPO-R plays a crucial role in the commitment of
hematopoietic stem cells into erythroid lineage cells.
PMID- 10195569
TI - Cytokine-induced expansion of human CD34+ stem/progenitor and CD34+CD41+ early
megakaryocytic marrow cells cultured on normal osteoblasts.
AB - Thrombocytopenia remains a significant cause of morbidity in cancer patients
undergoing allogeneic bone marrow transplantation (BMT), which consumes millions
each year for frequent platelet transfusions. Using a novel culture system
containing appropriate cytokine(s) on a layer of normal human osteoblasts, we
investigated the expansion of early megakaryocytic progenitor cells while
maintaining the number of CD34+ stem/progenitor marrow cells in an attempt to
provide an effective solution for the problem of post-transplant
thrombocytopenia. After seven days of culture, normal human osteoblasts alone
without cytokines significantly increased the number of CD34+ and CD34+CD41+
marrow cells. Among the various cytokine combinations tested, both stem cell
factor (SCF), interleukin 3 (IL-3)+IL-11 and SCF+IL-3+IL-11+thrombopoietin (TPO)
emerged as the most effective in expanding early CD34+CD41+ megakaryocytic cells.
Early CD34+CD41+ megakaryocytic cells have increased by 3.1- and 4.7-fold
compared with day 7 control cultures, and by 62- and 94-fold, respectively,
compared with day 0 input, respectively. Also, late CD41+ megakaryocytic cells
have increased by 15.4- and 27.5-fold compared with day 7 control cultures in the
presence of the same two combinations. In addition, the same cytokine
combinations achieved 17.6- and 13.3-fold increases in the number of CD34+ marrow
cells after the same seven days of culture on a layer of human osteoblasts. The
combination (SCF+IL-3+IL-11+TPO) achieved the highest expansion of CD34+CD41+
early megakaryocytic cells from human marrow CD34+ cells reported so far in the
literature. Recently, transplantation of SCF+IL-1+IL-3+TPO ex vivo expanded
megakaryocytic progenitor cells as a supplement has been shown to accelerate
platelet recovery by three to five days in mice. Therefore, the clinical use of
the combination (SCF+IL-3+IL-11+TPO) for ex vivo expansion of CD34+ and
megakaryocytic progenitor cells from a portion of the donor's marrow harvest is
warranted in allogeneic BMT. Such a protocol would accelerate platelet recovery
and shorten the period of hospitalization after allogeneic BMT. The present study
has confirmed the role of human osteoblasts in supporting the proliferation and
maintenance of human CD34+ stem/progenitor marrow cells. Given the facilitating
role of osteoblasts shown previously in several allogeneic BMT studies in mice,
it is possible to envisage a future role for donor osteoblasts in clinical BMT.
Transplantation of the cultured donor osteoblasts together with the ex vivo
expanded CD34+ marrow cells as a supplement might not only accelerate platelet
recovery but also prevent acute graft-versus-host disease in allogeneic BMT. The
present novel culture system should have useful clinical application in
allogeneic BMT.
PMID- 10195570
TI - In vitro effect of acetyl-N-Ser-Asp-Lys-Pro (AcSDKP) analogs resistant to
angiotensin I-converting enzyme on hematopoietic stem cell and progenitor cell
proliferation.
AB - The tetrapeptide Acetyl-N-Ser-Asp-Lys-Pro (AcSDKP), an inhibitor of hematopoietic
stem cell proliferation, is known to reduce in vivo the damage resulting from
treatment with chemotherapeutic agents or ionizing radiation on the stem cell
compartment. Recently, AcSDKP has been shown to be a physiological substrate of
the N-active site of angiotensin I-converting enzyme (ACE). Four analogs of the
tetrapeptide expressing a high stability towards ACE degradation in vitro have
been synthesized in order to provide new molecules likely to improve the
myeloprotection displayed by AcSDKP. These analogs are three pseudopeptides with
a modified peptidic bond, Ac-Serpsi(CH2-NH)Asp-Lys-Pro, Ac-Ser-Asppsi(CH2-NH)Lys
Pro, Ac-Ser-Asp-Lyspsi(CH2-N)Pro, and one C-terminus modified peptide (AcSDKP
NH2). We report here that these analogs reduce in vitro the proportion of murine
colony-forming units-granulocyte/macrophage in S-phase and inhibit the entry into
cycle of high proliferative potential colony-forming cells. The efficacy of
AcSDKP analogs in preventing in vitro primitive hematopoietic stem cells from
entering into cycle suggests that these molecules could be new candidates for the
powerful inhibition of hematopoietic stem and progenitor cell proliferation in
vivo.
PMID- 10195571
TI - Stimulation of adult human bone marrow by factors secreted by fetal liver
hematopoietic cells: in vitro evaluation using semisolid clonal assay system.
AB - Fetal liver infusion (FLI) therapy has been used in various disorders, such as
aplastic anemia, leukemia, metabolic disorders, etc., and has been shown to
result in stimulation of autologous hematopoiesis in many cases. The aim of the
present study was to elucidate the mechanism of stimulation of adult
hematopoiesis by fetal liver hematopoietic cells (FLHC) and to identify the
factors involved in the process using a clonal assay system in vitro. The effect
of FLHC on the clonal growth of bone marrow cells was studied using a co-culture
system consisting of mitomycin C-treated FLHC with 2 x 10(5) bone marrow (BM)
mononuclear cells. It was observed that FLHC induced a two- to four-fold increase
in the BM colony formation. A further increase in the number of FLHC did not,
however, result in an equivalent fold increase in the colony formation,
indicating that the number of cells in the BM population responsive to FLHC was
perhaps the limiting factor. When the effect of fetal liver cell conditioned
medium (FLCM) was examined in a similar fashion, it was observed that the FLCM
showed a 1.5- to 4-fold increase in the colony formation when used at 1%-5% along
with limiting amounts of growth factors. Higher concentrations of conditioned
medium resulted in inhibitory responses. One of the principal factors responsible
for the stimulatory activity of FLCM was shown to be transforming growth factor
beta1 (TGF-beta1), by a variety of experiments such as its quantitation in FLCM
by enzyme-linked immunosorbent assay, antibody neutralization, and reconstruction
experiments using purified TGF-beta1 and normal medium. In these reconstitution
experiments, TGF-beta1 stimulated the colony formation when it was applied at 1
50 pg/ml, but at higher concentration it induced an inhibitory effect, mimicking
the behavior earlier seen with FLCM. Our data strongly suggest that one of the
mechanisms in stimulation of a recipient's hematopoiesis could be mediated by the
action of TGF-beta1 secreted by infused FLHC and could provide a rational
framework on which FLI therapy can be further evaluated.
PMID- 10195572
TI - Recombinant adeno-associated virus-based vectors provide short-term rather than
long-term transduction of primitive hematopoietic stem cells.
AB - Bone marrow stem cells collected from B6-Gpi-1a mice pretreated with 5
fluorouracil were incubated for 2 h at 37 degrees C in the presence of the
recombinant adenovirus-associated virus-based vector (rAAV) SSV9. As measured in
vitro immediately following transduction, SSV9 was found to be effective in
transducing the primitive cobble-stone-area-forming cell (CAFC)-35 subset (60%
transduction efficiency). However, this did not predict long-term expression as
the presence of the transgene could not be detected six months after
transplantation of 1-2 x 106 transduced bone marrow stem cells into lethally
irradiated recipients. CAFC analysis of bone marrow cells and Southern blot
analysis of bone marrow and spleen cells were negative, and polymerase chain
reaction analysis showed less than 0.1% transduction in bone marrow cells.
Therefore, based on our study we conclude that rAAV transiently transduces
hematopoietic stem cells but fails to integrate into the genome, leading to the
loss of the reporter gene within the first six months after transplantation in
vivo.
PMID- 10195573
TI - Expression of platelet-activating factor receptor transcript-1 but not transcript
2 by human bone marrow cells.
AB - The presence of platelet-activating factor receptor (PAF-R) transcripts 1 and 2
was investigated in human bone marrow cells by a reverse transcriptase polymerase
chain reaction (RT-PCR) procedure which detected their simultaneous presence. RT
PCR experiments reveal PAF-R transcript 1 (but not 2) in freshly isolated
mononuclear marrow cells, CD34+ hematopoietic stem/progenitor cells and cultured
marrow stromal cells. For these experiments, the 5637 human bladder carcinoma
cell line is used as a positive control for the presence of PAF-R transcripts 1
and 2. Flow cytometry experiments confirm the presence of PAF-R on marrow stromal
cells and CD34+ stem/progenitor cells. In conclusion, the expression of PAF-R
transcript 1, which mainly exists in circulating leukocytes, is also found in
CD34+ stem/progenitor cells and cells of the marrow microenvironment,
strengthening the potential role of PAF during marrow hematopoiesis.
PMID- 10195574
TI - Cotinine (a metabolite of nicotine) suppresses the growth of hematopoietic
progenitor cells at the concentration range equivalent to its serum levels in
smokers.
PMID- 10195575
TI - High-resolution, multiple gradient-echo functional MRI at 1.5 T.
AB - A multiple gradient echo, high resolution imaging method is proposed to better
visualize different sources of activation in functional magnetic resonance
imaging (fMRI) experiments. Eight echoes are collected from 30 ms to 205 ms with
an echo spacing of 25 ms. All echoes show significant activation, but each echo
reveals its own pattern of activation. From this variability, it appears that
large vessel contributions can be separated from small vessel contributions using
a fuzzy cluster analysis across echo times. The results demonstrate the
importance of a multiple gradient echo data acquisition approach in localizing
various vascular contributions to brain activation in fMRI.
PMID- 10195576
TI - An evaluation of the time dependence of the anisotropy of the water diffusion
tensor in acute human ischemia.
AB - We have performed MRI examinations to determine the water diffusion tensor in the
brain of six patients who were admitted to the hospital within 12 h after the
onset of cerebral ischemic symptoms. The examinations have been carried out
immediately after admission, and thereafter at varying intervals up to 90 days
post admission. Maps of the trace of the diffusion tensor, the fractional
anisotropy and the lattice index, as well as maps of cerebral blood perfusion
parameters, were generated to quantitatively assess the character of the water
diffusion tensor in the infarcted area. In patients with significant perfusion
deficits and substantial lesion volume changes, four of six cases, our
measurements show a monotonic and significant decrease in the diffusion
anisotropy within the ischemic lesion as a function of time. We propose that
retrospective analysis of this quantity, in combination with brain tissue
segmentation and cerebral perfusion maps, may be used in future studies to assess
the severity of the ischemic event.
PMID- 10195577
TI - Correlation of regional cerebral blood flow from perfusion MRI and spect in
normal subjects.
AB - The objective of this study was to determine the relationship in regional
cerebral blood flow (rCBF) as measured with perfusion magnetic resonance imaging
(pMRI) and single photon emission computer tomography (SPECT). rCBF was
determined in 26 healthy subjects with pMRI and SPECT. After co-registration of
pMRI with SPECT, rCBF was determined in 10 brain regions relative to the whole
slice value. pMRI was evaluated with and without elimination of large vessels.
rCBF from pMRI correlates significantly with rCBF from SPECT (r = 0.69 with and r
= 0.59 without elimination of large vessels; p < 0.0001 for both). Elimination of
large vessels reduced the interindividual variance of the pMRI measurements in
most regions. rCBF from pMRI shows good correlation with rCBF from SPECT. Because
pMRI is sensitive to flow in large vessels while SPECT is not, elimination of
large vessels in pMRI reduces the interindividual variability of pMRI and
improves the-correlation between the two methods. pMRI is a reliable noninvasive
method for rCBF measurements.
PMID- 10195578
TI - Perfusion imaging of the human lung using flow-sensitive alternating inversion
recovery with an extra radiofrequency pulse (FAIRER).
AB - Pulmonary perfusion is an important parameter in the evaluation of lung diseases
such as pulmonary embolism. A noninvasive MR perfusion imaging technique of the
lung is presented in which magnetically labeled blood water is used as an
endogenous, freely diffusible tracer. The perfusion imaging technique is an
arterial spin tagging method called Flow sensitive Alternating Inversion Recovery
with an Extra Radiofrequency pulse (FAIRER). Seven healthy human volunteers were
studied. High-resolution perfusion-weighted images with negligible artifacts were
acquired within a single breathhold. Different patterns of signal enhancement
were observed between the pulmonary vessels and parenchyma, which persists up to
TI = 1400 ms. The T1s of blood and lung parenchyma were determined to be 1.46s
and 1.35 s, respectively.
PMID- 10195579
TI - Quantitative 3D VUSE pulmonary MRA.
AB - The purposes of this study were to quantitatively evaluate a free-breathing three
dimensional (3D) variable angle uniform signal excitation (VUSE) magnetic
resonance angiography (MRA) technique in normal volunteers, to demonstrate
breathold 3D VUSE MRA in a normal volunteer, and to investigate the ability of
the free-breathing 3D VUSE MRA technique to quantify differential flow in lung
transplant patients. A free-breathing 3D VUSE MRA pulse sequence was run on the
right lungs of 15 normal volunteers and both lungs of eight single or double lung
transplant patients. A breathold scan was also used on one volunteer. No contrast
agents were used. Normal lung MRA images were analyzed for maximum level of
branching observed and minimum distance between distal vessels seen and the
pleura. In patients, differential flow was determined with a program that counted
the number of MRA pixels over a threshold signal level in each lung. These values
were compared to radionuclide perfusion (Q) scan results. Average observed
branching order in normal lung images was 5.9 +/- 0.7. Average distance between
the most peripheral vessels seen and the pleura was 0.9 cm. Differential blood
flow measured by pulmonary MRA was well correlated with that measured by Q scan
(R2 = 0.84, p < 0.005). In addition to providing good visualization of normal
pulmonary vessels, this technique was demonstrated to provide accurate estimates
of differential blood flow in lung transplant patients free of serious lung
scarring.
PMID- 10195580
TI - MR imaging of cervical spine motion with HASTE.
AB - The HASTE (half-Fourier acquisition single-shot turbo spin-echo) technique
delivers images with T2-weighting in about half a second and could be ideal for
fast dynamic studies when T2-weighting is needed. We evaluated cardiac-triggered
HASTE to study cervical spine flexion/extension. The cervical spines of ten
asymptomatic volunteers were studied during flexion/extension motion on a 1.5
Tesla imager using a cardiac triggered version of the HASTE technique. Midline
sagittal images were acquired every 2 to 3 s during neck flexion and extension.
Image quality was compared to traditional T2-weighted Turbo spin-echo. The study
duration per flexion/ extension was typically less than 20 seconds and well
tolerated. The cardiac-gated T2-weighted HASTE images compared favorably to the
traditional T2-weighted TSE images in quality and overall anatomic detail. Range
of motion averaged: flexion 30 degrees (range 8 degrees -48 degrees) and
extension 23 degrees (range 0 degrees -57 degrees ). Greatest motion occurred in
the lower cervical spine (C4-C7). At the intervertebral discs the canal diameter,
anterior and posterior CSF spaces were widest in neutral position and decreased
with flexion and extension. Therefore, Cardiac-gated T2 HASTE sequences provide
diagnostic and time-efficient dynamic MR images of cervical spine motion.
PMID- 10195581
TI - MRI with superparamagnetic iron oxide: efficacy in the detection and
characterization of focal hepatic lesions.
AB - The purpose of this study was to evaluate the potential of superparamagnetic iron
oxide particles (SPIO) as tissue specific contrast agent in magnetic resonance
(MR) imaging in detection and characterization of focal hepatic lesions. We
investigated 45 patients with focal hepatic lesions. T1-weighted SE (TR 650/TE 15
ms) and T2-weighted SE (TR 2015-2030/TE 45 and 90 ms) unenhanced images were
obtained. After SPIO application we performed T1-weighted images with and T2
weighted images with and without fat suppression using the same image parameters.
Liver signal intensity decreased by 74% (min 47%, max 83%) on T2-weighted images
after application of the contrast agent. Benign lesions (FNH, adenoma) showed an
average signal drop of 40% (min 20%, max 47%) whereas malignant lesions showed no
significant change of signal intensity on post-contrast images. The mean tumor-to
liver contrast-to-noise ratio (C/N) was improved in all post-contrast sequences
irrespective of the lesion type. An additional increase of tumor-to-liver
contrast by use of fat suppression technique could be established in the slightly
T2-weighted sequence (TE 45 ms). In metastases, divided in different size groups,
we could determine a significant size relation of tumor-to-liver C/N. After SPIO
application the number of detected lesions increased distinctly, especially small
foci are more easily demonstrated. SPIO particles are a efficacious contrast
agent for MR examinations of the liver. For tumor characterization T1- and T2
weighted pre- and post-contrast images are necessary. The T1-weighted sequences
are helpful to differentiate benign lesions such as cysts and hemangiomas from
malignant lesions. Detection and differential diagnoses of hepatic lesions are
improved by use of the SPIO-particles.
PMID- 10195582
TI - Measurement of proliferation activity in human melanoma xenografts by magnetic
resonance imaging.
AB - Tumor proliferation may be predictive for malignant progression and response to
fractionated therapy of cancer. The purpose of the present work was to
investigate whether the proliferation activity of solid tumors can be assessed in
vivo from the proton relaxation times, T1 and T2. Tumors of four amelanotic human
melanoma xenograft lines were studied. Three parameters were used to represent
tumor proliferation activity; the volume doubling time, Tvol, the potential
doubling time, Tpot, and the fraction of cells in S-phase. Tvol was determined
from volumetric growth data. Tpot and S-phase fraction were determined by flow
cytometric analysis of tumor cells after bromodeoxyuridine (BrdU) incorporation
in vivo. T1 and T2 were measured by 1H-MRI in vivo, using spin-echo pulse
sequences. The proliferation parameters and relaxation times differed
considerably among the tumor lines. Significant correlations were found between
the proliferation parameters and the relaxation times, regardless of whether
Tvol, Tpot, or S-phase fraction was considered. Tumors with short Tvol and Tpot
and high S-phase fraction had long T1 and T2 compared to tumors with long Tvol
and Tpot and low S-phase fraction. The elongated T1 and T2 of fast growing tumors
were probably due to increased interstitial and/or intravascular water content.
The present results suggest that in vivo spin-echo 1H-MRI can be used to
discriminate between tumors of high and low proliferation activity.
PMID- 10195583
TI - Optimization of tissue segmentation of brain MR images based on multispectral 3D
feature maps.
AB - The purpose of this work was to optimize and increase the accuracy of tissue
segmentation of the brain magnetic resonance (MR) images based on multispectral
3D feature maps. We used three sets of MR images as input to the in-house
developed semi-automated 3D tissue segmentation algorithm: proton density (PD)
and T2-weighted fast spin echo and, T1-weighted spin echo. First, to eliminate
the random noise, non-linear anisotropic diffusion type filtering was applied to
all the images. Second, to reduce the nonuniformity of the images, we devised and
applied a correction algorithm based on uniform phantoms. Following these steps,
the qualified observer "seeded" (identified training points) the tissue of
interest. To reduce the operator dependent errors, cluster optimization was also
used; this clustering algorithm identifies the densest clusters pertaining to the
tissues. Finally, the images were segmented using k-NN (k-Nearest Neighborhood)
algorithm and a stack of color-coded segmented images were created along with the
connectivity algorithm to generate the entire surface of the brain. The
application of pre-processing optimization steps substantially improved the 3D
tissue segmentation methodology.
PMID- 10195584
TI - Characterization of human head vasculature by percolation parameters.
AB - A data reduction procedure, originally proposed for characterization of fractals
and random percolation clusters, has been used to evaluate the vascular system of
the human head. The motivation behind this study arose from the wish to study
empirically transport properties of vascular systems and to find a suitable
formalism for their description. MR angiographic data acquired by a standard 3D
inflow method were used. The evaluated parameters refer to the backbone fractal
dimensionality and the correlation length. The fractal dimensionality of the
backbone was found to be 1.71 for the human head vasculature. This value fits the
theoretical range of random percolation networks. It is concluded that concepts
of percolation theory might have some value for characterizing the structure and
transport properties of the vascular system.
PMID- 10195585
TI - Effects of vigabatrin intake on brain GABA activity as monitored by spectrally
edited magnetic resonance spectroscopy and positron emission tomography.
AB - A deficit in gamma-aminobutyric acid (GABA) levels in the brain or the
cerebrospinal fluid (CSF) is found in many epilepsy patients. Frequency and
severity of seizures may be reduced by treatment with GABA increasing medicaments
as e.g. vigabatrin, an irreversible inhibitor of GABA-transaminase. For a better
understanding of the associated effects, healthy volunteers were examined with
magnetic resonance spectroscopy (MRS) and positron emission tomography (PET)
before and after intake of different doses of vigabatrin. For the MRS
examinations, a dedicated localized spectral editing method was developed to
determine GABA levels. The 11C-flumazenil (FMZ)-PET protocol allowed
determination of GABA-A receptor binding. The results show a clear and dose
dependent increase in the brain GABA levels after the medication period as
compared to the baseline values. The GABA-A receptor binding, on the other hand,
did not change significantly.
PMID- 10195586
TI - Effects of gender and region on proton MRS of normal human brain.
AB - Localized, in vivo 1H magnetic resonance spectroscopy has been performed in a
number of brain regions of neuropsychiatric interest in male and female control
subjects to determine if gender and region affect the measured metabolite ratios.
In contrast to some previous reports, no significant differences were seen in any
region for any metabolite ratio between males and females. As expected,
significant variations with brain region were seen for metabolite ratios for the
total group of subjects.
PMID- 10195587
TI - A hybrid technique for spectroscopic imaging with reduced truncation artifact.
AB - Traditionally, Fourier spectroscopic imaging is associated with a small k-space
coverage which leads to truncation artifacts such as "bleeding" and ringing in
the resultant image. Because substantial truncation artifacts mainly arise from
regions having intense signals, such as the subcutaneous lipid in the head,
effective reduction of truncation artifacts can be achieved by obtaining an
extended k-space coverage for these regions. In this paper, a hybrid technique
which employs phase-encoded spectroscopic imaging (SI) to cover the central
portion of the k-space and echo-planar spectroscopic imaging (EPSI) to measure
the peripheral portion of the k-space is developed. EPSI, despite its inherently
low SNR characteristics, provides a sufficient SNR for outer high-spatial
frequency components of the aforementioned high signal regions and supplies an
extended k-space coverage of these regions for the reduction of truncation
artifacts. The data processing includes steps designed to remove inconsistency
between the two types of data and a previously described technique for
selectively retaining only outer k-space information for the high signal regions
during the reconstruction. Experimental studies, in both phantoms and normal
volunteers, demonstrate that the hybrid technique provides significant reduction
in truncation artifacts.
PMID- 10195588
TI - Quantitative magnetic resonance imaging of fresh and frozen-thawed trout.
AB - Magnetic resonance imaging (MRI) has been used to visualise the major organs and
muscular-skeletal frame-work of fresh rainbow trout (Salmo gairdneri) in two
dimensions, and to identify the spatial distribution of lipid- and collagen-rich
tissues. Quantitative MRI provides the MR parameters (T1, T2, M0, T1sat, Msat/M0,
and the Magnetisation Transfer (MT) rate) for the tissue water; variations in
those parameters enable distinction to be made between a freshly killed trout and
one which has been frozen-thawed. The effects of freezing method, repeat freeze
thawing, and storage time on the MR parameters are discussed.
PMID- 10195589
TI - A longitudinal study comparing the sensitivity of CSE and RARE sequences in
detecting new multiple sclerosis lesions.
AB - In this longitudinal study, we evaluated the sensitivities of dual-echo,
conventional spin-echo (CSE), and rapid-acquisition relaxation-enhanced (RARE)
scans for detecting the appearance of new lesions in multiple sclerosis (MS).
Dual echo, CSE, and RARE scans were obtained on four occasions each separated by
28 days from five patients with relapsing-remitting MS using a 1.5-Tesla machine.
A total of 44 new lesions were detected by the two sequences. Thirty-five lesions
were seen on both sequences, three only on CSE and six only on FSE. This study
indicates that CSE may be substituted by RARE when monitoring short-term disease
activity in MS.
PMID- 10195590
TI - Lesion load measurements in multiple sclerosis: the effect of incorporating
magnetization transfer contrast in fast-FLAIR sequence.
AB - We compared the ability and reproducibility of a fast fluid-attenuated inversion
recovery (fast-FLAIR) sequence with and without a magnetization transfer (MT)
pulse for detecting and measuring multiple sclerosis (MS)-related abnormalities
on magnetic resonance imaging (MRI) scans from 20 patients. The Contrast-to-Noise
ratios between lesions and normal-appearing white matter, lesion numbers, lesion
volumes and the variability of such measurements were similar for the two
sequences. This suggests that the addition of MT to FLAIR sequences as currently
implemented on standard MRI scanners does not improve the detection of MS
lesions.
PMID- 10195591
TI - Three-dimensional magnetic resonance imaging of the interosseous membrane of
forearm: a new method using fuzzy reasoning.
AB - We now report newly developed three-dimensional magnetic resonance imaging (3D
MRI) system which is based on semiautomatic tissue extraction from the axial MR
images utilizing the fuzzy reasoning calculation method and 3D-image
reconstruction with surface rendering. We also studied normal in vivo dynamic
changes of the interosseous membrane (IOM) of forearm during rotation using this
3D-MRI. Serial axial MRI of right forearms of five healthy volunteers was
obtained in five rotational positions, and extraction and 3D-reconstruction of
the radius, ulna, and IOM was made using the system. Extraction results were well
with the fuzzy reasoning method. 3D-MRI of the radius and ulna, IOM were
reconstructed from these images respectively, and their 3D-shapes were almost
identical to the anatomic shape. 3D-MRI showed there were wavy deformities on the
IOM in pronation position in the all five subjects and dorsiflexion on the most
dorsal portion of the IOM at maximum supination in three forearms. In neutral
position, the IOM of all five volunteers was almost flat. From anatomic
orientation, these dynamic changes of the IOM mainly occurred at the membranous
portion, which is soft, thin, and elastic. Otherwise, the tendinous portion which
is a thick and strong complex of 5 to 10 bundles run from proximal one third of
the radius to distal one fourth of the ulna, demonstrated minimal dynamic changes
on the 3D-MRI. Therefore, the tendinous portion is considered to be taut during
rotation to provide stability between the radius and the ulna, while the
membranous portion is easy to deform and allowing smooth rotation. Furthermore,
because of wide-use, our 3D-MRI system is useful for in vivo analysis of soft
tissue kinesiology in normal and abnormal musculoskeletal systems.
PMID- 10195592
TI - Improvement of the acquisition of a large amount of MR images on a conventional
whole body system.
AB - Modern whole body MR systems are equipped with echo-planar-imaging capability,
which allows the measurement of a single slice in a fraction of a second or of
thousands of images in few minutes. A considerable restriction to the acquisition
of series containing large amounts of images in patient examinations is the time
consuming data handling time of the images at conventional systems, which
includes the time to insert the images into the systems database. We propose the
arrangement of several images on a new image with a large matrix size like a
mosaic. The handling time depends mostly on the number of images without
consideration of their matrix size. Therefore, image handling is strongly reduced
by the use of such mosaic images.
PMID- 10195593
TI - Intrahepatic arterioportal fistula: gadolinium-enhanced 3D magnetic resonance
angiography findings and angiographic embolization with steel coils.
AB - We describe a case of a 59-year-old patient with intrahepatic arterioportal
fistula secondary to blunt trauma sustained by a motor vehicle accident 36 years
earlier. The fistula was demonstrated 36 years after the accident in a clinical
work-up for diarrhea of 1 month's duration, using contrast enhanced three
dimensional breath-hold MRA. A communication between the dilated portal vein and
dilated hepatic artery was shown at the level of distal branches. After
subsequent demonstration by conventional angiography, the fistula was embolized
using steel coils. Following the therapeutic intervention, the patient's diarrhea
ceased.
PMID- 10195594
TI - Primary lymphoma of the breast: MR imaging features. A case report.
AB - Primary non-Hodgkin's lymphoma (NHL) of the breast are rare and represent less
than 0.6% of all mammary malignancies. Secondary involvement of the breast in
patients with diffuse disease occurs more frequently. The radiologic features of
breast lymphoma are nonspecific, and the diagnosis is based on histologic
criteria. We present the MR-imaging features of a case of primary NHL of the
breast.
PMID- 10195595
TI - Re: Serial precision of metabolite peak area ratios and water referenced
metabolite peak areas in proton MR spectroscopy of the human brain Simmons et al
1996, vol. 16, pages 319-330 1998.
PMID- 10195596
TI - Prevention of obesity in American Indian children: the Pathways study.
PMID- 10195597
TI - The epidemic of obesity in American Indian communities and the need for childhood
obesity-prevention programs.
AB - American Indians of all ages and both sexes have a high prevalence of obesity.
The high prevalence of diabetes mellitus in American Indians shows the adverse
effects that obesity has in these communities. Obesity has become a major health
problem in American Indians only in the past 1-2 generations and is believed to
be associated with the relative abundance of high-fat foods and the rapid change
from active to sedentary lifestyles. Intervention studies are urgently needed in
American Indian communities to develop and test effective strategies for weight
reduction. The poor success rate of adult obesity treatment programs in the
general population points to the need to develop prevention approaches aimed
toward children. Because eating and physical activity practices are formed early
in life and may be carried into adulthood, prevention programs that encourage
increased physical activity and healthful eating habits targeted toward young
people need to be developed and tested. To be most effective, interventions must
be developed with full participation of the American Indian communities.
PMID- 10195598
TI - Practicing participatory research in American Indian communities.
AB - The purpose of this article is to explore the historical issues that affect
research in American Indian communities and examine the implications of these
issues as they relate to culturally sensitive, respectful, and appropriate
research with this population. Methods include review and analysis of the
literature and examination of our collective experience and that of our
colleagues. Recommendations are given for conducting culturally sensitive,
participatory research. We conclude that research efforts must build on the
establishment of partnerships between investigators and American Indian
communities to ensure accurate findings and analyses and to implement culturally
relevant benefits.
PMID- 10195599
TI - Design and statistical analysis for the Pathways study.
AB - We report the design, rationale, and statistical procedures used in Pathways, a
randomized, school-based intervention for the primary prevention of obesity in
American Indian children. The intervention, which is now being implemented in 7
American Indian communities around the country, includes a health-promotion
curriculum, a physical education program, a school meal program, and a family
involvement component. Forty-one schools serving American Indian children were
randomly assigned to be either intervention or control groups. The intervention
will begin in the third grade and continue through the end of the fifth grade.
Efficacy of intervention will be assessed by differences in mean percentage body
fat, calculated by a prediction equation, between intervention and control
schools at the end of the fifth grade. Power computations indicate that the study
has power to detect a mean difference of 2.8% in body fat. Data analysis will use
intention-to-treat concepts and the mixed linear model. The study will be
completed in 2000.
PMID- 10195600
TI - Body composition assessment in American Indian children.
AB - Although the high prevalence of obesity in American Indian children was
documented in several surveys that used body mass index (BMI, in kg/m2) as the
measure, there is limited information on more direct measurements of body
adiposity in this population. The present study evaluated body composition in 81
boys (aged 11.2+/-0.6 y) and 75 girls (aged 11.0+/-0.4 y) attending public
schools in 6 American Indian communities: White Mountain Apache, Pima, and Tohono
O'Odham in Arizona; Oglala Lakota and Sicangu Lakota in South Dakota; and Navajo
in New Mexico and Arizona. These communities were participating in the
feasibility phase of Pathways, a multicenter intervention for the primary
prevention of obesity. Body composition was estimated by using a combination of
skinfold thickness and bioelectrical impedance measurements, with a prediction
equation validated previously in this same population. The mean BMI was 20.4+/
4.2 for boys and 21.1+/-5.0 for girls. The sum of the triceps plus subscapular
skinfold thicknesses averaged 28.6+/-7.0 mm in boys and 34.0+/-8.0 mm in girls.
Mean percentage body fat was 35.6+/-6.9 in boys and 38.8+/-8.5 in girls. The
results from this study confirmed the high prevalence of excess body fatness in
school-age American Indian children and permitted the development of procedures,
training, and quality control for measurement of the main outcome variable in the
full-scale Pathways study.
PMID- 10195601
TI - Multisite formative assessment for the Pathways study to prevent obesity in
American Indian schoolchildren.
AB - We describe the formative assessment process, using an approach based on social
learning theory, for the development of a school-based obesity-prevention
intervention into which cultural perspectives are integrated. The feasibility
phase of the Pathways study was conducted in multiple settings in 6 American
Indian nations. The Pathways formative assessment collected both qualitative and
quantitative data. The qualitative data identified key social and environmental
issues and enabled local people to express their own needs and views. The
quantitative, structured data permitted comparison across sites. Both types of
data were integrated by using a conceptual and procedural model. The formative
assessment results were used to identify and rank the behavioral risk factors
that were to become the focus of the Pathways intervention and to provide
guidance on developing common intervention strategies that would be culturally
appropriate and acceptable to all sites.
PMID- 10195602
TI - Development of a questionnaire to assess knowledge, attitudes, and behaviors in
American Indian children.
AB - One aim of the Pathways study is to improve the knowledge, attitudes, and
behaviors of American Indian children in grades 3-5 regarding physical activity
and diet in. This article describes the development of a culturally sensitive,
age-appropriate questionnaire to assess these variables. The questionnaire was
designed to be administered in the classroom in two 30-min sessions. Questions
were developed to assess 4 key areas: physical activity, diet, weight-related
attitudes, and cultural identity. Potential questions were written after review
of relevant literature and existing questionnaires. Numerous and extensive
revisions were made in response to input from structured, semistructured, and
informal data collection. Questions were pretested in 32 children in grades 3-5
by using semistructured interviews. Test-retest reliability and the internal
consistency of scales were examined in 371 fourth-grade children and subsequently
in 145 fourth-grade children. Questions were reviewed by American Indians from
the communities involved in the Pathways study several times during the
developmental process. The process described here serves as one model for the
development of a culturally appropriate tool to assess knowledge, attitudes, and
behaviors in American Indian children.
PMID- 10195603
TI - Portion-size estimation training in second- and third-grade American Indian
children.
AB - Training in portion-size estimation is known to improve the accuracy of dietary
self-reporting in adults, but there is no comparable evidence for children. To
obtain this information, we studied 110 second- and third-grade American Indian
schoolchildren (34 control subjects were not trained), testing the hypotheses
that a 45-min portion-size estimation training session would reduce children's
food quantity estimation error, and that the improvement would be dependent on
food type, measurement type, or both. Training was a hands-on, 4-step estimation
and measurement skill-building process. Mixed linear models (using logarithmic
transformed data) were used to evaluate within- and between-group differences
from pre- to posttest. Test scores were calculated as percentage estimation
errors by difference and absolute value methods. Mean within-group estimation
error decreased significantly (P<0.05) from pre- to posttest for 7 of 12 foods
(trained group) by both calculation methods, plus 3 additional foods by the
difference method and one additional food by the absolute value method.
Significant (P<0.05) between-group differences occurred for 3 foods, reflecting a
greater decrease in estimation error for the trained group. Improvement was
greatest for solid foods estimated by dimensions (P>0.05) or in cups (P<0.05),
for liquids estimated by volume or by label reading (P<0.001), and for one
amorphous food estimated in cups (P<0.01). Despite these significant improvements
in estimation ability, the error for several foods remained >100% of the true
quantity, indicating that more than one training session would be necessary to
further increase dietary reporting accuracy.
PMID- 10195604
TI - Physical activity assessment in American Indian schoolchildren in the Pathways
study.
AB - The objective of the Pathways physical activity feasibility study was to develop
methods for comparing type and amount of activity between intervention and
control schools participating in a school-based obesity prevention program. Two
methods proved feasible: 1) a specially designed 24-h physical activity recall
questionnaire for assessing the frequency and type of activities and 2) use of a
triaxial accelerometer for assessing amount of activity. Results from pilot
studies supporting the use of these methods are described. Analyses of activity
during different segments of the day showed that children were most active after
school. The activities reported most frequently (e.g., basketball and mixed
walking and running) were also the ones found to be most popular in the study
population on the basis of formative assessment surveys. Both the physical
activity recall questionnaire and the triaxial accelerometer methods will be used
to assess the effects of the full-scale intervention on physical activity.
PMID- 10195605
TI - Pathways: a culturally appropriate obesity-prevention program for American Indian
schoolchildren.
AB - Pathways, a culturally appropriate obesity prevention study for third-, fourth-,
and fifth-grade American Indian schoolchildren includes an intervention that
promotes increased physical activity and healthful eating behaviors. The Pathways
intervention, developed through a collaboration of universities and American
Indian nations, schools, and families, focuses on individual, behavioral, and
environmental factors and merges constructs from social learning theory with
American Indian customs and practices. We describe the Pathways program developed
during 3 y of feasibility testing in American Indian schools, with special
emphasis on the activities developed for the third grade; review the theoretical
and cultural underpinnings of the program; outline the construction process of
the intervention; detail the curriculum and physical education components of the
intervention; and summarize the formative assessment and the school food service
and family components of the intervention.
PMID- 10195606
TI - Pathways family intervention for third-grade American Indian children.
AB - The goal of the feasibility phase of the Pathways family intervention was to work
with families of third-grade American Indian children to reinforce health
behaviors being promoted by the curriculum, food service, and physical activity
components of this school-based obesity prevention intervention. Family behaviors
regarding food choices and physical activity were identified and ranked according
to priority by using formative assessment and a literature review of school-based
programs that included a family component. The family intervention involved 3
primary strategies designed to create an informed home environment supportive of
behavioral change: 1) giving the children "family packs" containing worksheets,
interactive assignments, healthful snacks, and low-fat tips and recipes to take
home to share with their families; 2) implementing family events at the school to
provide a fun atmosphere in which health education concepts could be introduced
and reinforced; and 3) forming school-based family advisory councils composed of
family members and community volunteers who provided feedback on Pathways
strategies, helped negotiate barriers, and explored ideas for continued family
participation. For strategy 2, a kick-off Family Fun Night provided a series of
learning booths that presented the healthful behaviors taught by Pathways. At an
end-of-year Family Celebration, a healthy meal was served, students demonstrated
newly learned Pathways activities, and certificates were presented in recognition
of completion of the Pathways curriculum. Based on evaluation forms and
attendance rosters, strategies 1 and 2 were more easily implemented and better
received than strategy 3. Implications for developing family involvement
strategies for intervention programs are discussed.
PMID- 10195607
TI - The Pathways study: a model for lowering the fat in school meals.
AB - We describe the development and implementation of the Pathways school food
service intervention during the feasibility phase of the Pathways study. The
purpose of the intervention was to lower the amount of fat in school meals to 30%
of energy to promote obesity prevention in third- through fifth-grade students.
The Pathways nutrition staff and the food service intervention staff worked
together to develop 5 interrelated components to implement the intervention.
These components were nutrient guidelines, 8 skill-building behavioral
guidelines, hands-on materials, twice yearly trainings, and monthly visits to the
kitchens by the Pathways nutrition staff. The components were developed and
implemented over 18 mo in a pilot intervention in 4 schools. The results of an
initial process evaluation showed that 3 of the 4 schools had implemented 6 of
the 8 behavioral guidelines. In an analysis of 5 d of school menus from 3 control
schools, the lunch menus averaged from 34% to 40% of energy from fat; when the
menus were analyzed by using the food preparation and serving methods in the
behavioral guidelines, they averaged 31% of energy from total fat. This unique
approach of 5 interrelated food service intervention components was accepted in
the schools and is now being implemented in the full-scale phase of the Pathways
study in 40 schools for 5 y.
PMID- 10195608
TI - Process evaluation in a multisite, primary obesity-prevention trial in American
Indian schoolchildren.
AB - We describe the development, implementation, and use of the process evaluation
component of a multisite, primary obesity prevention trial for American Indian
schoolchildren. We describe the development and pilot testing of the instruments,
provide some examples of the criteria for instrument selection, and provide
examples of how process evaluation results were used to document and refine
intervention components. The theoretical and applied framework of the process
evaluation was based on diffusion theory, social learning theory, and the desire
for triangulation of multiple modes of data collection. The primary objectives of
the process evaluation were to systematically document the training process,
content, and implementation of 4 components of the intervention. The process
evaluation was developed and implemented collaboratively so that it met the needs
of both the evaluators and those who would be implementing the intervention
components. Process evaluation results revealed that observation and structured
interviews provided the most informative data; however, these methods were the
most expensive and time consuming and required the highest level of skill to
undertake. Although the literature is full of idealism regarding the uses of
process evaluation for formative and summative purposes, in reality, many persons
are sensitive to having their work evaluated in such an in-depth, context-based
manner as is described. For this reason, use of structured, quantitative, highly
objective tools may be more effective than qualitative methods, which appear to
be more dependent on the skills and biases of the researcher and the context in
which they are used.
PMID- 10195609
TI - Efficacy of Vi polysaccharide vaccine against Salmonella typhi.
PMID- 10195610
TI - Humoral and cellular immunity induced by antigens adjuvanted with colloidal iron
hydroxide.
AB - The immunopotentiating activities of colloidal iron hydroxide, a novel,
experimental mineral adjuvant, and of aluminium hydroxide. the licensed adjuvant
for human vaccines, were compared. Our studies revealed that colloidal iron
hydroxide and aluminium hydroxide behaved comparably with respect to supporting
induction of an antibody response to tetanus toxoid. Furthermore, mice immunized
with both, the experimental vaccine (tick-borne encephalitis virus (TBEV) antigen
adsorbed to colloidal iron hydroxide) or with a commercially available TBEV
vaccine (adjuvanted with aluminium hydroxide), developed long-lasting antibody
responses which protected the animals from TBEV infection even one year after
vaccination. The use of colloidal iron hydroxide as adjuvant had the additional
advantage to reproducibly support induction of HIV-1 envelope-specific cytotoxic
T lymphocytes (CTL), when used as adjuvant for a HIV-1 env-carrying recombinant
fowlpox virus and being applied via the subcutaneous route. Aluminium hydroxide
was much less active in this respect. Non-adjuvanted recombinant fowlpox elicited
CTLs only when given intravenously or intraperitoneally, vaccination routes
considered not to be suitable for routine use in humans. Further studies to
evaluate the use of colloidal iron as possible alternative and/or supplement for
routinely used mineral adjuvants may therefore be warranted.
PMID- 10195611
TI - Effect of vaccination against Mycoplasma hyopneumoniae in pig herds with an all
in/all-out production system.
AB - A multi-site field study was conducted to evaluate an inactivated Mycoplasma
hyopneumoniae (Mh) vaccine in 14 pig herds infected by Mh and practising an all
in/all-out production system. In each herd, a vaccinated and control group of 250
pigs each were compared during the growing/finishing period with respect to
performance parameters (major variables) and by means of clinical, serological
and pathological parameters (ancillary variables). Mh vaccination significantly
(P < 0.05) improved daily weight gain (+22 g), feed conversion ratio (-0.07),
medication costs (-0.476 ECU/pig) (1 ECU = US$1.0269542), prevalence of pneumonia
lesions (-14%) and severity of pneumonia lesions (-3%). Mortality rate, severity
of coughing and carcass quality were not significantly influenced by Mh
vaccination. Serological results of Mh and other respiratory pathogens are
presented and discussed. A cost-benefit analysis based on significantly improved
performance parameters demonstrated that Mh vaccination was economically
attractive as it resulted in an increase of the net return to labour with 1.300
ECU per finishing pig sold. The sensitivity of the economic benefit was
illustrated towards fluctuations in pig finishing prices.
PMID- 10195612
TI - Enhanced immunogenicity of hepatitis B surface antigen by insertion of a helper T
cell epitope from tetanus toxoid.
AB - The currently marketed hepatitis B vaccines in the U.S. are based on the
recombinant major hepatitis B surface antigen (HBsAg) of hepatitis B virus.
Although a large majority of individuals develop protective immunity to HBV
induced disease after three immunizations, routinely a small but a significant
percentage of the human population does not respond well to these vaccines. In
this report, we describe the generation of a novel HBsAg molecule containing a Th
epitope derived from tetanus toxoid (TT). Using recombinant DNA technology. the
TT Th epitope (TTe) was inserted into the HBsAg coding sequence. Using a
recombinant adenovirus expression system, HBsAg TTe chimeric protein was produced
in A549 cells and found to be secreted into culture medium as 22 nm particles.
The chimeric HBsAg particles were readily purified by immunoaffinity
chromatography and their immunogenicity was evaluated relative to native HBsAg
produced in an adenovirus expression system. When evaluated in inbred and outbred
strains of mice, HBsAg TTe was shown to enhance several-fold the anti-HBs
response relative to native HBsAg. Further enhanced responses were observed in
mice primed with TT. This highly immunogenic form of HBsAg has promise as an
improved HBsAg subunit vaccine.
PMID- 10195613
TI - Recent immunization against measles does not interfere with the sero-response to
yellow fever vaccine.
AB - In order to determine whether previous measles vaccination interferes with the
sero-response to yellow fever vaccine, 294 children at nine months of age were
randomly assigned to immunization with yellow fever vaccine at different time
intervals after measles vaccination. The seroconversion rate (SCR) and the log10
geometric mean titer (GMT) for 17 DD yellow fever vaccine at different intervals
after Schwarz measles vaccination were: 1-6 days: SCR = 44/57 = 77%; GMT = 4.57;
7-13 days: SCR = 36/53 = 68%; GMT = 4.46; 14-21 days: SCR = 55/65 = 85%; GMT =
4.46; 22-27 days: SCR = 41/54 = 76%; GMT = 4.41 and >28 days: SCR = 52/65 = 80%;
GMT = 4.24 (p > 0.05). We conclude that recent immunization against measles does
not interfere with the sero-response to yellow fever vaccine.
PMID- 10195615
TI - Production of a highly immunogenic subunit ISCOM vaccine against Bovine Viral
Diarrhea Virus.
AB - Bovine Viral Diarrhea Virus (BVDV) is a major pathogen of cattle in most
countries. The main reservoir of virus in herds are BVDV persistently infected
animals, which arise as a result of infection of the bovine fetus early in
gestation. The spread of virus to the unborn fetus may be prevented by
vaccination of the dam. We describe in this report the production and initial
testing of an inactivated subunit vaccine against BVDV. The vaccine is based on
production of antigen in primary bovine cell cultures, extraction of antigens
from infected cells with detergent, chromatographic purification, concentration,
and insertion of antigens into immune stimulating complexes (ISCOMs). Vaccines
based on two different Danish strains of BVDV were injected into calves and the
antisera produced were tested for neutralising activity against a panel of Danish
BVDV strains. The two vaccines induced different neutralisation responses, which
seem to partly complement each other. The implication of these observations for
successful vaccination against BVDV is discussed.
PMID- 10195614
TI - MHC class I- and class II-restricted processing and presentation of
microencapsulated antigens.
AB - Macrophages were found of having a strong capacity of phagocytosing small size
microcapsules (MS) and presenting microencapsulated antigens to either CD4+ and
CD8- T cells. The class I-restricted presentation of microencapsulated tetanus
toxoid by macrophages requires an intracellular processing which might follow the
phagosome-to-cytosol route to enter the classical MHC class I presentation
pathway. In contrast, presentation of microencapsulated cytotoxic peptide PbCS252
260 to specific CD8+ T cells has been observed with different APC and is not
blocked by cytochalasin D, suggesting that peptide released from MS may directly
bind to MHC class I molecules on the cell surface. In the case of MHC class II
restricted T cells, prefixation or treatment of macrophages with chloroquine,
brefeldin A and cycloheximide inhibits the presentation of microencapsulated and
soluble tetanus toxoid. These findings illustrate the capacity of
microencapsulated antigens to enter different presentation pathways and should
facilitate the development of subunit vaccines.
PMID- 10195616
TI - Biodegradable microspheres containing influenza A vaccine: immune response in
mice.
AB - A monovalent influenza split vaccine was microencapsulated in poly(D,L-lactic-co
glycolic acid) (PLGA) and ABA triblock copolymers using a W/O/W double emulsion
technique. To stabilize the antigen, influenza vaccine was also coencapsulated
with liposomes. Antigen release from microspheres was determined in vitro using a
hemagglutinin-specific ELISA. PLGA-microspheres with liposomes released
immunoreactive hemagglutinin in a pulsatile manner, a preferred feature for the
development of a single dose vaccine delivery system. Influenza hemagglutinin
specific IgG and neutralizing antibody responses were studied in BALB/c mice
following subcutaneous injection of different microsphere preparations. PLGA
microspheres elicited a significantly higher primary IgG response compared to
nonencapsulated antigen. ABA-microspheres seemed to be less immunogenic than PLGA
microspheres based on the IgG antibody response, however, similar levels of
neutralizing antibodies were observed after eight weeks with both polymers.
Entrapment of the antigen in liposomes prior to microencapsulation did not
further enhance the immune response. The immunopotentating effect of the antigen
loaded microspheres was prominently enhanced when they were given as suspension
in fluid antigen, suggesting that free antigen may serve as priming and
microencapsulated antigen as booster dose. Eight weeks after a single
subcutaneous immunization with PLGA or ABA-microspheres neutralizing antibodies
were as high as those obtained after two subcutaneous administrations of fluid
vaccine four weeks apart. Microencapsulated influenza antigen may have potential
for a single dose vaccine delivery system with adjuvant properties.
PMID- 10195617
TI - Mucosal and systemic immune responses induced after oral delivery of vaccinia
virus recombinants.
AB - The immune responses elicited after oral delivery of vaccinia virus (VV)
recombinants are not well defined. In this study we show with mice, that after
oral administration of a VV recombinant expressing the luciferase reporter gene,
VV gene expression takes place for several days in gut-associated lymphoid (GALT)
tissues as well as in the spleen. After 14 days, a significant mucosal IgA
response against VV was detected in vaginal and intestinal washings, as well as a
systemic specific IgG response, which was principally of the IgG2a subclass.
Furthermore, orally immunized mice developed cellular immune responses to VV
(CD8+ T cells and T helper activities) in mesenteric lymph nodes (MLN) and
spleen. Oral immunization with a VV recombinant expressing, either the envelope
protein of HIV or beta-galactosidase, induced a specific immune response, locally
and systemically, against gp120 and beta-gal. The cytokine pattern found in
supernatants of spleen and MLN cells after stimulation with VV antigens or gp120
was clearly of type 1 cytokines. These studies demonstrate that VV recombinants
administered by the oral route generate mucosal and systemic immune responses
against antigens of the virus vector and to the recombinant products. These
observations are of significance in the use of poxvirus vectors as vaccines.
PMID- 10195618
TI - Randomised, controlled trial with the trypsin-modified inactivated poliovirus
vaccine: assessment of intestinal immunity with live challenge virus.
AB - The enhanced potency inactivated poliovirus vaccine (E-IPV) was modified to
contain trypsin-treated type 3 poliovirus (PV3), strain Saukett, as the type 3
component (TryIPV). This pilot vaccine was previously shown to redistribute the
vaccine-induced antibody specificities in mice to mimic those seen in man after
poliovirus infection. Groups of infants were then immunised with three doses of
TryIPV or E-IPV in a randomised, double-blind trial. Six months after the third
dose, at the age of 18 months, the children were challenged with one dose of oral
monovalent type 3 poliovirus vaccine. Intestinal immunity was evaluated by
assessing the length and extent of PV3 excretion through determination of PV3
titres in 9 successive faecal specimens (2-42 days after challenge). No
significant difference in the length or extent of virus excretion was seen
between the groups. The results indicate that TryIPV, under the conditions used,
was no more potent than the regular E-IPV in inducing resistance to intestinal
poliovirus infection.
PMID- 10195619
TI - A novel immunization method to induce cytotoxic T-lymphocyte responses (CTL)
against plasmid-encoded herpes simplex virus type-1 glycoprotein D.
AB - DNA molecules complexed with an asialoglycoprotein-polycation conjugate,
consisting of asialoorosomucoid (ASOR) coupled to poly-L-lysine, can enter
hepatocytes which bear receptors for ASOR. We used this receptor-mediated DNA
delivery system to deliver plasmid DNA encoding glycoprotein D (gD) of herpes
simplex virus type 1 to ASOR-positive cells. Maximum expression of gD protein was
seen at 3 days after injection of this preparation in approximately 13% of cells
from BALB/c mice [hepatocytes from mice injected intravenously (i.v.) or
peritoneal exudate cells from mice injected intraperitoneally (i.p.)]. In
comparison with mice injected with either the plasmid vector alone or the gD
containing plasmid uncomplexed to ASOR, mice immunized with gD-containing plasmid
complexed with ASOR-poly-L-lysine induced marked antigen-specific CTL responses.
BALB/c mice immunized with gD-DNA developed a T-cell-mediated CTL response
against target cells expressing gD and MHC class II glycoproteins, but not
against cells expressing only gD and MHC class I molecules. In C3H mice, gD-DNA
induced a T-cell-mediated CTL response against target cells expressing gD and
class I MHC molecules. Serum anti-gD antibody in low titers were produced in both
strains of mice. DNA complexed with ASOR-poly-L-lysine induced CTL responses in
mice.
PMID- 10195621
TI - Immunization of dogs and cats with a DNA vaccine against rabies virus.
AB - The applicability of DNA immunization technology for vaccine development in
companion animals was investigated by immunizing dogs and cats by the
intramuscular (i.m.) and intradermal (i.d.) routes with a plasmid DNA vector
encoding the rabies virus glycoprotein G. In dogs, administration of 100 microg
DNA doses by the i.m. route resulted in stronger and more durable rabies virus
neutralizing antibody (RVNA) titers than those obtained by i.d. inoculation. In
contrast, i.m. vaccination of cats with a similar dose was less effective in
terms of mean titer and seroconversion frequency. However, efficacy was improved
by increasing the dosage to 300 microg of DNA per immunization. Interestingly,
i.d. inoculation of cats appeared to be a superior route of delivery in this
species, resulting in higher seroconversion frequency than i.m. administration.
In addition, geometric mean RVNA titers in i.d. inoculated cats increased over
four-fold during a seven month period following a second and final immunization.
These results demonstrate that non-facilitated, naked DNA vaccines can elicit
strong, antigen-specific immune responses in dogs and cats, and DNA immunization
may be a useful tool for future development of novel vaccines for these species.
PMID- 10195620
TI - A live attenuated chimeric recombinant parainfluenza virus (PIV) encoding the
internal proteins of PIV type 3 and the surface glycoproteins of PIV type 1
induces complete resistance to PIV1 challenge and partial resistance to PIV3
challenge.
AB - The recovery of wild type and attenuated human parainfluenza type 3 (PIV3)
recombinant viruses has made possible a new strategy to rapidly generate a live
attenuated vaccine virus fof PIV1. We previously replaced the coding sequences
for the hemagglutinin-neuraminidase (HN) and fusion (F) proteins of PIV3 with
those of PIV1 in the PIV3 antigenomic cDNA. This was used to recover a fully
viable, recombinant chimeric PIV3-PIV1 virus, termed rPIV3-1, which bears the
major protective antigens of PIV1 and is wild type-like with regard to growth in
cell culture and in hamsters [Tao T, Durbin AP, Whitehead SS, Davoodi F, Collins
PL, Murphy BR. Recovery of a fully viable chimeric human parainfluenza virus
(PIV) type 3 in which the hemagglutinin-neuraminidase and fusion glycoprotein
have been replaced by those of PIV type 1. J Virol 1998;72:2955-2961]. Here we
report the recovery of a derivative of rPIV3-1 carrying the three temperature
sensitive and attenuating amino acid coding changes found in the L gene of the
live-attenuated cp45 PIV3 candidate vaccine virus. This virus, termed rPIV3
1.cp45L, is temperature-sensitive with a shut-off temperature of 38 degrees C,
which is similar to that of the recombinant rPIV3cp45L, which possesses the same
three mutations. rPIV3-1.cp45L is attenuated in the respiratory tract of hamsters
to the same extent as rPIV3cp45L. Infection of hamsters with rPIV3-1.cp45L
generated a moderate level of hemagglutination-inhibiting antibodies against wild
type PIV1 and induced complete resistance to challenge with wild type PIV1. This
demonstrates that this novel attenuated chimeric virus is capable of inducing a
highly effective immune response against PIV1. It confirms previous observations
that the surface glycoproteins of parainfluenza viruses are sufficient to induce
a high level of resistance to homologous virus challenge. Unexpectedly, infection
with recombinant chimeric virus rPIV3-1.cp45L or rPIV3-1, each bearing the
surface glycoprotein genes of PIV1 and the internal genes of PIV3, also induced a
moderate level of resistance to replication of wild type PIV3 challenge virus.
This indicates that the internal genes of PIV3 can independently induce
protective immunity against PIV3 in rodents, albeit a lower level of resistance
than that induced by the surface glycoproteins. Thus, a reverse genetics system
for PIV3 has been used successfully to produce a live attenuated PIV1 vaccine
candidate that is attenuated and protective in experimental infection in
hamsters.
PMID- 10195622
TI - Cross-protective efficacy of a bovine viral diarrhea virus (BVDV) type 1 vaccine
against BVDV type 2 challenge.
AB - A new genotype of bovine viral diarrhea virus (BVDV), designated BVDV type 2
(BVDV 2), has become prevalent in the field. BVDV 2 strains are antigenically
distinct from currently available vaccine strains of the BVDV 1 genotype, raising
concerns about cross-protection of these vaccines against BVDV 2 challenge. To
determine cross-protective efficacy of a modified-live virus (MLV) vaccine
containing BVDV 1 strain WRL (BVDV 1(WRL)), two studies were conducted in which
the relative magnitude and duration of BVDV 1- and BVDV 2-specific serologic
responses and protection against BVDV 2 challenge were determined. For the first
study, 27 heifers were vaccinated (13 i.m. and 14 s.c.), while 13 heifers
received negative control vaccine. Serum from the vaccinated heifers neutralized
both BVDV 1 and BVDV 2 strains. The evolution and duration of BVDV 1 and BVDV 2
serologic responses were comparable, and antibody titers to BVDV 2 persisted
through at least 105 days post-single vaccination. In a second, separate study,
17 calves were vaccinated (9 i.m. and 8 s.c.), and 11 calves were held as
unvaccinated controls. Approximately seven months following vaccination, the
calves were challenged intranasally with the 890 isolate of BVDV 2. Clinical
signs of disease and fever were significantly reduced in vaccinates in comparison
with controls. Vaccination eliminated nasal virus shedding in 87% of cattle and
completely prevented viremia and leukopenia. These data indicate utility of BVDV
1(WRL) MLV vaccine in stimulation of long-term BVDV 2-specific serologic
responses, protection against BVDV 2 challenge and reduction or elimination of
virus shedding which can contribute to spread of BVDV 2 in herds.
PMID- 10195623
TI - Evaluation of a new recombinant DNA hepatitis B vaccine (Shanvac-B).
AB - We assessed the efficacy and safety of Shanvac-B, a new recombinant hepatitis B
vaccine developed in India. Eighty-one healthy volunteers (75 women, 6 men; aged
18-40 yr), negative for markers for hepatitis B and HIV, received 20 microg of
the vaccine intramuscularly at 0, 1 and 2 months. Forty-three (53%) seroconverted
at one month after dose 1; of these, 26% were seroprotected (anti-HBs> 10
mIU/mL). Seroprotection at one month after doses 2 and 3 was 99% and 100%,
respectively. Geometric mean titres of anti-HBs in subjects who seroconverted
were 11 (range 2-366), 266 (8-7469) and 2246 (102-23680) mIU/mL, respectively.
One subject developed urticarial rash after the second dose; there was no other
adverse event. We conclude that this vaccine is safe and efficacious, providing
significant protection even after two doses.
PMID- 10195624
TI - Comparison between targeted and untargeted systemic immunizations with adjuvanted
urease to cure Helicobacter pylori infection in mice.
AB - Outbred OF1 mice infected in a first step with a mouse-adapted Helicobacter
pylori strain were immunized in a second step by systemic or mucosal routes:
systemic immunizations were performed subcutaneously with adjuvanted urease
either in the infra or supra-diaphragmatic region of the body, while mucosal
immunization was done with urease in the presence of E. coli heat Labile toxin.
Mucosal and subcutaneous immunizations induced in infected mice a significant
reduction in bacterial density whatever the site of injection but complete
eradication was preferentially observed in mice immunized subcutaneously in the
back. Systemic immunization with appropriate schedules and formulations could
constitute a valuable approach to cure Helicobacter pylori infection.
PMID- 10195625
TI - Enhanced cellular immunity to hepatitis C virus nonstructural proteins by
codelivery of granulocyte macrophage-colony stimulating factor gene in
intramuscular DNA immunization.
AB - Hepatitis C virus (HCV) nonstructural (NS) proteins appeared to be important
targets for HCV vaccine development, since NS-specific T-helper-cell responses
are associated with clearance from acute HCV infection. In this report, we have
constructed a plasmid, pTV-NS345, that encodes the HCV NS3, NS4 and NS5 proteins
(NS345) and a bicistronic plasmid, PTV-NS345/GMCSF, in which the HCV NS345
polyprotein and GMCSF are translated independently. Intramuscular inoculation
with pTV-NS345 plasmid DNA into the Buffalo rats generated both antibody and T
cell proliferative responses to each NS protein. The expression of GMCSF,
together with HCV NS345 proteins, appeared to significantly increase T-cell
proliferative responses. In particular, the inoculation of a bicistronic plasmid
generated higher T-cell proliferative responses to each NS protein than did the
coinjection of two separate plasmids, pTV-NS345 and pTV-GMCSF. These results
demonstrate that the codelivery of GMCSF augmented HCV NS345-specific cellular
immunity and that the intensity of the immunity was differed depending on how
GMCSF gene is codelivered.
PMID- 10195626
TI - Defective immune response to tetanus toxoid in hemodialysis patients and its
association with diphtheria vaccination.
AB - The incidence of infectious diseases is increased in patients with chronic renal
failure. This is thought to be due to an impaired T cell stimulation by antigen
presenting cells. Immunization programs are of great significance in the
prevention of infections in immunocompromised individuals. However, the immune
response to various vaccinations is impaired in patients with chronic renal
failure. So far only few studies have focused on seroresponse to tetanus toxoid.
Therefore we measured the levels of antitetanus toxoid antibodies in 71
hemodialysis patients with unknown vaccination history. The antibody levels were
detected prior to and twelve months after a single "Td" or "Td-d-d" vaccination.
Initially only 31 (44%) of the patients had a sufficient protection against
tetanus. Of the unprotected patients 15 (38%) seroconverted after immunization,
while 25 (63%) did not respond. We found a high association (p < 0.04, Fisher's
exact test) between the efficacy of vaccination against diphtheria and tetanus.
Out of 38 initially unprotected patients 27 (71%) showed a similar response to
both vaccines: 9 (24%) individuals seroconverted, while 18 (47%) did not. Our
data clearly demonstrate the need for frequent monitoring of antibody levels
after immunization against tetanus and diphtheria in hemodialysis patients.
PMID- 10195627
TI - Expression, processing, and immunogenicity of the structural proteins of
Venezuelan equine encephalitis virus from recombinant baculovirus vectors.
AB - Recombinant baculoviruses expressing the structural proteins of Venezuelan equine
encephalitis virus (VEE) have been constructed and the intracellular processing,
antigenicity, and immunogenicity of the expression products have been assessed.
Baculoviruses expressing the entire structural protein region (C-E3-E2-6K-E1), or
the complete glycoprotein region (E3-E2-6K-E1), generated products in Sf9 cells
that were accurately and completely processed, and resulted in mature proteins
that were antigenically and electrophoretically indistinguishable from authentic
viral proteins. These products were highly immunogenic in BALB/c mice, induced
efficient VEE neutralizing responses, and protected these animals against
challenge with virulent VEE. Expression of individual glycoprotein regions (E3-E2
and 6K-E1) generated products that were accurately but incompletely processed,
and induced non-neutralizing antibodies that reacted more efficiently with
denatured than native VEE proteins. Nonetheless, immunization with the 6K-E1
expression product provided complete protection against VEE challenge.
PMID- 10195628
TI - Prevention of infection of influenza virus in DQ6 mice, a human model, by a
peptide vaccine prepared according to the cassette theory.
AB - We proposed a strategy (cassette theory) in which non-binding peptides for murine
major histocompatibility complex (MHC) class II molecules are introduced into a
MHC-binding component to render the resultant hybrid peptides bound to the MHC
and thus immunogenic in animals carrying the relevant MHC. It was shown that
46F/HA127-133/54A(18mer) peptide which was prepared by introducing hemagglutinin
(HA)127-133 of influenza virus into the H-2Ab binding component induced
significant T cell responses and antibodies (Ab) specific for HA127-133 in H-2Ab
mice. Further we found that the H-2Ab binding component had a supermotif for
human class II molecules (i.e. HLA-DQ6). In the present study, a new peptide
vaccine, H3-H3, was prepared by combining 46F/HA127-133/54A(18mer) as a carrier
and HA127-133 attached to the C terminus of 46F/HA127-133/54A(18mer) as a hapten
and the effect of vaccine was examined in DQ6 mice which carry HLA-DQ6 alone as
MHC class II molecules and thus may be regarded as a model of the DQ6 positive
individuals. Since 46F/HA127-133/ 54A(18mer) induced merely Ab against HA127-133,
it was assumed that H3-H3 induced mainly HA127-133 specific Ab in DQ6 mice
without undesirable Ab production against the carrier. Indeed, H3-H3 elicited T
cell responses and induced HA127-133 specific Ab in DQ6 mice. Furthermore,
administration of H3-H3 inhibited growth of influenza virus until 9 weeks after
the last immunization in DQ6 mice.
PMID- 10195629
TI - Haemophilus influenzae type b conjugate vaccine stability: catalytic
depolymerization of PRP in the presence of aluminum hydroxide.
AB - The structural stability of the Haemophilus influenzae type b (Hib) capsular
polysaccharide, polyribosylribitolphosphate (PRP) in an aluminum hydroxide
adsorbed, polysaccharide-protein conjugate vaccine was monitored using
modifications of an HPLC assay developed by Tsai et al. [Tsai C-M, Gu X-X, Byrd
RA. Quantification of polysaccharide in Haemophilus influenzae type b conjugate
and polysaccharide vaccines by high-performance anion-exchange chromatography
with pulsed amperometric detection. Vaccine 1993;12:700-706.]. As applied to
products containing PRP conjugated to the outer membrane protein complex (OMPC)
from Neisseria meningitidis, this assay allows direct measurement of the total
PRP content in very complex samples including commercial vaccine products. In
addition, with the use of a high-speed centrifugation step, the assay can be used
to directly quantify any PRP that is not conjugated to the OMPC carrier protein.
These results provide evidence of what appears to be a catalytic reaction taking
place between the phosphodiester bond of PRP and the aluminum hydroxide adjuvant
that results in hydrolysis of the PRP polymer into smaller chain lengths and
liberation of PRP oligomers from the conjugate particle. The reaction approaches
an asymptotic limit after approximately two years at 2-8 degrees C. Clinical
studies which span this time period confirm that the modest decrease in
conjugated PRP content over time does not impact the overall clinical
effectiveness of PRP-OMPC-containing vaccines.
PMID- 10195630
TI - Evaluation of the stability and immunogenicity of autoclaved and nonautoclaved
preparations of a vaccine against American tegumentary leishmaniasis.
AB - This study was designed to evaluate the immunogenicity of autoclaved and
nonautoclaved preparations of a vaccine composed of whole antigens from killed
promastigotes of Leishmania amazonensis. Leishmanin skin-test (LST)-negative
volunteers were immunized with either autoclaved or nonautoclaved vaccine
preparations (32 and 36 subjects, respectively) that had been maintained at 4
degrees C for one year before the onset of this trial. Immunological tests were
performed two days before and 40 days after vaccination. The LST conversion rates
induced by the autoclaved and nonautoclaved vaccines were significantly
different: 59% and 83%, respectively. Leishmania antigen-stimulated proliferative
responses of peripheral blood mononuclear cells (PBMC) were significantly higher
after vaccination than before vaccination in both groups. The CD8+ subset was
predominant over the CD4+ subset among the leishmania-reactive cells after
vaccination in both groups. The production of IFN-gamma by the leishmania antigen
stimulated PBMC was significantly higher after vaccination than before
vaccination in the group receiving the nonautoclaved vaccine but not in the
autoclaved vaccine group. IL-2 was found both before and after vaccination with
no differences between its levels in these time points in either group. IL-4 was
not detected for either group during the study period.
PMID- 10195631
TI - Secondary vaccination with vaccinia virus recombinants: role of residual
virulence of recombinants and immunogenicity of extrinsic antigens.
AB - ICR mice were immunized intraperitoneally with two doses (10(6) PFU per dose) of
vaccinia virus (VV) recombinants of variable virulence expressing either the
strongly immunogenic glycoprotein E (gE) of varicella zoster virus (VZV) or
weakly immunogenic hepatitis B virus (HBV) preS2-S (S) antigen. Recombinants
expressing gE were able to elicit primary and secondary anti-gE antibody
irrespective of their residual virulence; after the second dose they did so even
in the presence of VV antibody resulting from primary vaccination dose or under
other conditions limiting VV replication. As for the S-recombinants, pronounced
anti-S antibody development was only observed in mice which had received the more
virulent recombinant virus as the first dose. A repeated dose of S-recombinants
was unable to elicit a secondary anti-S antibody response. The present findings
do not support the assumption that the poor immunogenicity of some extrinsic
antigens could be overcome by administering repeated doses of the particular VV
recombinant.
PMID- 10195632
TI - Activation of spleen lymphocytes by plasmid DNA.
AB - Plasmid pUC19 DNA was shown to stimulate in vitro proliferation of CBA mouse
splenocytes in a dose-dependent manner. Simultaneous treatment of the cells with
the plasmid DNA and Con A or LPS produced an additive effect, while PMA acted
synergistically with DNA. Monovalent Fab fragments of rabbit anti-mouse Ig
(RAMIg) antibodies significantly inhibited plasmid DNA-induced polyclonal
lymphocyte activation suggesting the involvement of Ig receptors in this process.
Affinity modification of lymphocytes membrane-cytosole proteins with a 32P
labeled alkylating oligonucleotide derivative resulted in labeling of 67-82 and
23 kDa polypeptides corresponding to IgD and IgM heavy and light chains
respectively. The immunoglobulin nature of the 82 and 23 kDa oligonucleotide
binding polypeptides was confirmed by immunoprecipitation with RAMIg antibodies.
PMID- 10195633
TI - Pan DR binding sequence provides T-cell help for induction of protective
antibodies against Plasmodium yoelii sporozoites.
AB - Pan-DR epitope (PADRE) peptides have demonstrated the capacity to deliver help
for antibody responses in vivo. They were also found, fortuitously, to be able to
provide significant helper T-cell activity in vivo. This suggested that linear
constructs, containing the PADRE epitope, might be as efficient at generating an
immune response as large multivalent antigens. Plasmodium falciparum and P.
yoelii PADRE constructs were capable of inducing a high titre IgG antibody
response that recognized intact sporozoites. We now report that these antibodies
can inhibit sporozoite invasion of hepatocytes in vitro and that mice immunized
with the PyCSP-PADRE linear construct were protected when challenged with P.
yoelii sporozoites.
PMID- 10195634
TI - Intra-nasal infection of macaques with Yellow Fever (YF) vaccine strain 17D: a
novel and economical approach for YF vaccination in man.
AB - Investigating new and simple application routes for YF vaccine, four groups of 4
6 rhesus monkeys were vaccinated with live attenuated 17D YF-vaccine. In two
groups the vaccine was administered either as spray into the oral cavity, or as
an encapsulated form directly into the stomach. Only one out of eight animals
developed a humoral immune response against 17D. In the third group receiving the
vaccine intranasally by spray and in the fourth group serving as control all ten
monkeys developed an immune response. From all except one of these seroconverted
monkeys virus could be detected either by virus reisolation or RT-PCR. All these
animals showed a serological immune response in immunofluorescence and
neutralisation test. Parallel to viremia, an increase of neopterin as an
unspecified immune activation marker could be demonstrated for these animals.
Intra-nasal application of 17D-vaccine seems to be a good alternative to
subcutaneous immunisation in mass vaccination campaigns.
PMID- 10195635
TI - The business of science and the science of business in the quest for an AIDS
vaccine.
AB - This paper simplifies and encapsulates the past, present and future for
developing vaccines, especially against AIDS. Needed technical information and
how it can best be obtained are delineated. The views are my own and may not be
shared by others. The science enterprise, including that for vaccines, is
enmeshed in the major evolution and restructuring of many of the world's
institutions. Changes brought by the knowledge revolution impinge on scientific
information, technology, public policy, societal demands, private and public
funding, academic and industrial organization and economic opportunity. Public
supported research is not an entitlement. It is in the scientific establishment's
best interest to organize for greatest efficiency and effectiveness to bring
paybacks commensurate with public investment.
PMID- 10195636
TI - A novel influenza subunit vaccine composed of liposome-encapsulated
haemagglutinin/neuraminidase and IL-2 or GM-CSF. I. Vaccine characterization and
efficacy studies in mice.
AB - The aim of this study was to improve the potency of the currently used influenza
subunit vaccines, which are of relatively low efficiency in high-risk groups.
Influenza A virus (Shangdong/9/93) haemagglutinin/neuraminidase (H3N2),
granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-2 (IL
2) were encapsulated, each separately or combined, in multilamellar vesicles
composed of dimyristoyl phosphatidylcholine. BALB/c mice were immunized once,
i.p. or s.c., with 0.05-2.0 microg HN administered either as free antigen (F-HN),
adsorbed to aluminum hydroxide (Al-HN), or encapsulated in liposomes (Lip-HN),
separately or together with 1 x 10(2)-4.5 x 10(4) units of free or encapsulated
cytokines. Serum antibodies were assayed on days 11-360 by the haemagglutination
inhibition (HI) test and ELISA. Protective immunity against intranasal virus
challenge was determined at 9-14 months post-vaccination. The following results
were obtained: (1) The efficiency of encapsulation in liposomes was 95, 90 and
38% for HN, IL-2 and GM-CSF, respectively, and the liposomal preparations were
highly stable as an aqueous dispersion for > 2 months at 4 degrees C. (2)
Following immunization with 0.5 microg Lip-HN, there was an earlier, up to 50
fold stronger, and 3-5 times longer response than that obtained with nonliposomal
HN. (3) Coimmunization with free cytokines further increased the response 2-20
times and the two cytokines had an additive effect. (4) Liposomal cytokines were
2-20 times more effective than the free cytokines and their stimulatory effect
was more durable. (5) A 100% seroconversion (HI titer > or = 40) was achieved
with only 10-25% of the routinely used antigen dose, by encapsulating either
antigen or cytokine. (6) The level of protection following vaccination with the
combined liposomal vaccines was 70-100% versus 0-25% in mice immunized with Al-HN
alone, and no toxicity was observed. In conclusion, our animal experiments show
that the liposomal vaccines are superior to the currently used influenza
vaccines, increasing the response by 2-3 orders of magnitude in mice. This
approach may also prove valuable for subunit vaccines against other
microorganisms.
PMID- 10195637
TI - A novel influenza subunit vaccine composed of liposome-encapsulated
haemagglutinin/neuraminidase and IL-2 or GM-CSF. II. Induction of TH1 and TH2
responses in mice.
AB - This study was aimed at analyzing, in parallel, the humoral and cellular immune
responses elicited in mice immunized with liposomal influenza A (Shangdong/9/93)
subunit vaccines composed of haemagglutinin/neuraminidase (H3N2) and IL-2 or GM
CSF. Recently, we reported that such vaccines evoke a more rapid, stronger and
longer-lasting (over 1 year) humoral response, as well as protective immunity
against viral infection, following a single administration, as compared with the
response induced by the free antigen given alone or together with soluble
cytokines. In the present study, BALB/C mice were immunized once, i.p., s.c.,
i.m. or i.n., with nonliposomal or liposomal vaccines and the humoral (antibody
titer and isotypes) and cellular (DTH, cytotoxicity, cytokine production)
responses were assessed at various times (2-56 weeks). The main findings were:
(a) the combined liposomal vaccines consisting of encapsulated antigen and
encapsulated cytokine, but not the free antigen, elicited a high titer of serum
IgG1, IgG2a, IgG3 and IgM antibodies; (b) the combined liposomal vaccines were
efficient following administration by the various routes, and induced a local (in
lung) IgA response in i.n. vaccinated mice; (c) the liposomal vaccines triggered
DTH and cytotoxic responses, as well as cytokine (mainly IL-4) production.
Together, these and other findings indicate that our cytokine-supported liposomal
influenza vaccines efficiently stimulate both Th1 and Th2 responses and that such
vaccines may be more potent in high-risk groups than the currently used subunit
vaccines.
PMID- 10195638
TI - Size fractionation of bacterial capsular polysaccharides for their use in
conjugate vaccines.
AB - We have developed a chromatographic method suitable for the fractionation of
polysaccharides having a negatively charged group. The method permits the removal
of all those polysaccharide fragments having a short sequence and which are
likely unsuitable for conjugate vaccine construction. The selected polysaccharide
fragments can be used to produce glycoconjugate vaccines containing a restricted
saccharide polydispersion. We have applied this chromatographic method to three
different antigens, Haemophilus influenzae type b and Neisseria meningitidis
group A and group C polysaccharides. The method is easily adapted for
manufacturing purposes.
PMID- 10195639
TI - Vaccination of pigs against pseudorabies virus with plasmid DNA encoding
glycoprotein D.
AB - We analysed the ability of a plasmid carrying the gene encoding glycoprotein D
(gD) of pseudorabies virus (PRV) to induce humoral and cell-mediated immune
responses and assessed the protection provided by PRV-gD DNA vaccination against
challenge infection with PRV. Immunization with plasmid PRV-gD induced
neutralizing antibodies and lymphocyte proliferative responses both in mice and
pigs. Moreover, when challenged with virulent PRV six weeks following the last
immunization, PRV-gD DNA vaccinated pigs excreted virus for a significantly
shorter period and showed less clinical symptoms than pigs vaccinated with a
control plasmid. Thus, in the target animal, DNA vaccination with PRV-gD DNA
induces protective immunity against challenge infection.
PMID- 10195640
TI - Construction and murine immunogenicity of recombinant Bacille Calmette Guerin
vaccines expressing the B subunit of Escherichia coli heat labile enterotoxin.
AB - Three recombinant strains of Mycobacterium bovis Bacille Calmette Guerin (rBCG)
were prepared in which the immunogenic B subunit of human Escherichia coli heat
labile enterotoxin (LT-Bh) was expressed either as a cytoplasm protein, a cell
wall associated lipoprotein or a secreted protein. Intraperitoneal immunisation
of mice with these rBCG induced IgG and IgA antibodies to LT-Bh and shifted the
serum IgG subclass response to subsequent challenge with purified LT-Bh from IgG1
to an IgG2a. Oral administration of recombinant BCG induced mucosal and serum IgA
antibodies to LT-Bh which peaked four months after immunisation. Antibody
responses were greater when LT-Bh was expressed as a secreted protein or
lipoprotein rather than in the cytoplasm. Oral vaccination with recombinant BCG
may be an effective approach, particularly to induce mucosal IgA and prime for a
serum TH1 recall response.
PMID- 10195642
TI - The trigonometric regressive spectral analysis--a method for mapping of beat-to
beat recorded cardiovascular parameters on to frequency domain in comparison with
Fourier transformation.
AB - Heart rate and peripheral blood pressure as physiological recorded vegetative
parameters are very often rhythmically investigated with the Fourier
Transformation (FT). In contrast to the original use of FT these parameters are
still stochastic with overlaying rhythmical structures. The R-R intervals as
independent variables of time are not equidistant. The mathematical structure for
the spectral decomposition is critically analysed. The purpose of this article is
the presentation of a mathematical method, considering both the statistical and
rhythmical features of such time series. On the basis of trigonometric
regressions, this method is presented to eliminate the equidistance problems,
arising with the usage of FT, by a new mathematical approach. This method
computes more precisely the spectral power especially in the VLF range (0.003
0.04 Hz) than FT, because this method of trigonometric regression does not
perform a frequency quantization. This method has been used and successfully
tested for the analysis of peripheral blood pressure and R-R intervals including
an effective reduction of input data.
PMID- 10195641
TI - The major Epstein-Barr virus (EBV) envelope glycoprotein gp340 when incorporated
into Iscoms primes cytotoxic T-cell responses directed against EBV lymphoblastoid
cell lines.
AB - A recombinant form of the EBV envelope glycoprotein and vaccine candidate gp340,
lacking its hydrophobic transmembrane region, was incorporated into Iscoms after
coupling to phosphatidyl ethanolamine via carbohydrate residues. Coupling by
partial oxidation of gp340 carbohydrate with sodium periodate partly denatured
the incorporated gp340 as indicated by its reduced reactivity with monoclonal
antibodies that recognise the major neutralising epitope. Immunisation of
cottontop tamarins with these Iscoms elicited antibody responses to gp340, but
these antibodies only poorly recognised the major neutralising epitope in a
competition ELISA and were unable to neutralise EBV in vitro. Despite the lack of
neutralising antibody, immunisation with these Iscoms primed significant in vitro
proliferative responses to soluble gp340 in lymphocytes from the draining lymph
nodes and spleen. T-cell lines were raised from both immunised and control
animals by in vitro stimulation of peripheral blood lymphocytes or spleen cells
with autologous EBV-transformed lymphoblastoid cell lines. The T-cell lines from
control animals had higher numbers of CD4+ T-cells than CD8+ T-cells and were not
cytotoxic for autologous lymphoblastoid cell lines (LCL). In contrast the lines
from immunised animals contained more CD8+ T-cells than CD4+ T-cells and had
marked cytotoxicity for autologous LCL.
PMID- 10195643
TI - Computing measures of explained variation for logistic regression models.
AB - The proportion of explained variation (R2) is frequently used in the general
linear model but in logistic regression no standard definition of R2 exists. We
present a SAS macro which calculates two R2-measures based on Pearson and on
deviance residuals for logistic regression. Also, adjusted versions for both
measures are given, which should prevent the inflation of R2 in small samples.
PMID- 10195644
TI - GEECAT and GEEGOR: computer programs for the analysis of correlated categorical
response data.
AB - GEECAT and GEEGOR are two user-friendly SAS macros for the analysis of clustered,
correlated categorical response data. Both programs implement methodology which
extend the generalized estimating equation (GEE) approach of Liang and Zeger
(Biometrika 73 (1986) 13-22). GEECAT and GEEGOR both use a first set of
estimating equations to model the marginal response. With GEECAT, either
correlated nominal or ordered categorical response data can be analyzed. The
program GEEGOR employs a second set of estimating equations to model the
association of ordered categorical responses within a cluster using the global
odds ratio as a measure of association. The programs run on both mainframe
computers and microcomputers. Examples are provided to illustrate the features of
both programs.
PMID- 10195645
TI - CORA--a knowledge-based system for the analysis of case-control studies.
AB - Carrying out a statistical analysis, the researcher is concerned with the problem
of choosing an appropriate statistical technique from a large number of competing
methods. Most common statistical software offer different methods for analysing
the data without giving any support regarding the adequacy of a method for a
particular data set. This paper outlines the main features of the computer system
CORA which provides a statistical analysis of stratified contingency tables and
additionally supports the researcher at the different steps of this analysis.
Here, the support given by the system consists of two different aspects. On the
one hand, the help system of CORA contains general information on the implemented
statistical methods which can be obtained on request. On the other hand, an
advice tool recommends an adequate statistical method which depends on the actual
empirical case-control data to be analysed. To build up the advice tool, a set of
rules being discovered by machine learning from simulation studies is integrated
into the system CORA.
PMID- 10195646
TI - Xpose--an S-PLUS based population pharmacokinetic/pharmacodynamic model building
aid for NONMEM.
AB - The building of population pharmacokinetic/pharmacodynamic (PK/PD) models is a
time consuming and complicated task. This is partly due the lack of specialized
tools for the visualization and exploration requirements of this type of
analysis. In this paper we present Xpose, a model building aid for population
PK/PD analysis using NONMEM, which simplifies the task of producing
documentation, data set checkout plots, goodness of fit plots and graphical model
comparison. It also facilitates covariate model building by the use of stepwise
generalized additive modeling (GAM), bootstrap of the GAM analyses and tree based
modeling. The plots and analyses are presented in the form of a text based menu
system and the only thing the user has to do is to make NONMEM produce one or
more table files named in a specific way.
PMID- 10195647
TI - An EXCEL-based method to search for potential Ser/Thr-phosphorylation sites in
proteins.
AB - A user-friendly, inexpensive EXCEL-based program to find potential
phosphorylation sites in proteins is presented. The input of the program is a
protein sequence in single letter code. The program searches for 93 different
protein kinase recognition sites from 30 different protein kinases. The output is
a list of these sites and their position in the sequence. The program can easily
be updated in case new recognition sites are described. With a few adaptations,
the tool can also be used to find other patterns in a protein sequence.
PMID- 10195648
TI - Classification of urinary stones by cluster analysis of ionic composition data.
AB - The cluster analysis technique is considered for classifying kidney stones based
on data for nine chemical analysis parameters. A set of 214 stones is used, which
has been previously classified using empirical classification rules into three
stone types using the percentage concentrations of the urate, oxalate, and
phosphate radicals. We investigate whether cluster analysis utilising data on all
parameters leads to different classifications and explore the possibility of
other effective classifiers. We also compare the performance of various
clustering techniques, distance and similarity measures and data standardisation
methods. Results indicate that inclusion of the additional six parameters does
not improve the classification accuracy. Best matching with the empirical
classification (6% error) is achieved using the average linkage (between groups)
clustering method and the squared Eculidean distance measure without data
standardisation. Excluding these three main radicals causes a 63% matching error.
Cluster analysis results suggest that carbon ions alone provide a single
classifier for the three stone types, giving a matching error of approximately
10% with the empirical classification.
PMID- 10195649
TI - Segregation analysis of quantitative traits.
AB - A review of advanced methods of segregation analysis of quantitative traits on
human pedigree data is presented. Special attention was paid to formulation of
genetic models tested in the analysis, to the possibility of statistical
distinguishing between these models, to the power of the used transmission
probability tests, and to the possibility of unambiguous interpretation of the
analysis results.
PMID- 10195650
TI - A case for reduced skin sensation in high latitude prehistoric Polynesians.
AB - The cranial sensory nerve supply in three skeletal populations, two distinct
prehistoric Polynesian groups from New Zealand, the Moriori and Maori, and one
contemporary Indian group, are investigated. This paper assesses an aspect of the
hypothesis that Polynesian groups have anatomical adaptations that enabled them
to survive in a cool and wet environment. To this end the relationship between
sensory nerve dimensions were examined, based on the area of cranial nerve
foramina, and external environmental temperature. Statistical comparisons between
the Polynesians and Indians showed significantly reduced cranial cutaneous
sensory nerve foramina size, and therefore diminished facial cutaneous sensory
nerve supply in the Polynesians. On this basis it is inferred that sensory supply
to the skin of the infracranial body was also lessened. This paper proposes that
reduced skin sensory nerve supply was selected as an adaptation to a cool and wet
environment, where it acted as a body energy conserving mechanism by delaying the
onset of body warming mechanisms.
PMID- 10195651
TI - Population structure of two black Venezuelan populations studied through their
mating structure and other related variables.
AB - In order to obtain information about the population structure of two black
Venezuelan populations with historical differences both in their origins and
development, a variety of variables were utilized, especially on marital
structure, including: frequency of surnames, isonymy, population genealogical
consanguinity, multiple unions, and marital distances, all of which provided
information and isolation, migration, endogamy, consanguinity, and patri
matrifocality. Results showed differences in the extent of isolation and
endogamy, as well as differences in population structure, which can be directly
related with historical conditions of each population. Results agree with those
previously obtained with traditional genetic polymorphisms and with the
historical information available. Thus, the usefulness of surnames for inferring
about population structure is supported, as well as the usefulness of historical
information for explaining genetic diversity.
PMID- 10195652
TI - Areas of fat loss in overweight young females following an 8-week period of
energy intake reduction.
AB - In order to investigate the main areas of fat loss after an 8-week period of
energy intake reduction, the distribution of body fat was assessed on 14 females
(BMI 27.3+/-0.83 kgm(-2)) (mean +/- SEM), aged 18-22 years. Total body fat was
determined by hydrostatic weighing and subcutaneous fat mass and distribution
were assessed using ultrasound and waist-hip circumference ratios prior to, and
following, an 8-week period during which subjects attempted to reduce their
energy intake by about 4.2 MJ day(-1). Subjects lost an average of 2.99+/-0.34 kg
(p < 0.001), with greater loss (p < 0.001) of internal fat (1.5+/-0.2 kg) than of
subcutaneous fat (0.7+/-0.1). Subjects reduced their waist-hip ratio from 0.771+/
0.01 to 0.762+/-0.01 (p < 0.01), their waist circumference from 807+/-24 to 790+/
23 mm (p < 0.001) and their hip circumference from 1047+/-29 to 1037+/-29 mm (p <
0.001). Those with an android distribution of fat (n = 5) lost more weight than
those with gynoid distribution (n = 9) (3.80+/-0.38 kg vs 2.54+/-0.14 kg, p <
0.05); they also showed a greater decrease in waist circumference (27+/-5 vs 14+/
4 mm, p < 0.05) and a greater loss from internal fat stores (2.1+/-0.3 kg vs
1.1+/-0.2 kg, p < 0.05). The findings suggest that individuals are prone to lose
internal fat during a short period of reduced energy intake. As the visceral fat
store is the largest internal fat depot in the body, this suggests that
individuals are indeed losing fat that could predispose to upper body obesity.
PMID- 10195654
TI - Age at menarche in Greek girls.
AB - This study reports menarcheal age in 1134 contemporary Greek girls and the
duration of their menstrual cycle. Comparison with a similar study performed 15
years ago shows that in Greek girls there is still a secular trend, although a
small one, towards earlier menarcheal age.
PMID- 10195653
TI - Past malaria, thalassemia and woman fertility in southern Italy.
AB - The role of natural selection in maintaining the thalassemia polymorphism is
examined in a southern Italy district, in the past affected by malaria endemia.
The Haldane's hypothesis that the thalassemia heterozygotes enjoy more protection
than the normal homozygotes against the risk of malaria infection, seems to be
confirmed by this indirect study at population level. The higher number of
children born of the women who lived in the highly endemic villages, where the
highest proportion of heterozygotes occurs, supports the hypothesis that the
woman fertility contributes to the thalassemia maintenance. The joint effects of
the acquired and inherited immunities and of the reproductive compensation are
assumed as the mechanisms through which malaria and thalassemia influence
fertility.
PMID- 10195655
TI - Hierarchical differences in body composition of professional Sumo wrestlers.
AB - The body composition of 36 professional Sumo wrestlers and 39 collegiate male
students were assessed densitometrically. The means of body weight, BMI and %fat
for Sumo wrestlers were 117.1 kg, 36.5 and 26.2%, extraordinarily large compared
with untrained men (p < 0.001). Results of the analysis of variance of divisions
of Sumo wrestlers revealed significant differences in body weight, fat-free mass,
fat mass, BMI, fat-free mass index (FFM/height2) and fat mass index (FM/height2).
For the visual expression of the hierarchical differences of body composition,
fat mass index and fat-free mass index of the wrestlers in various leagues were
plotted on a body composition chart. Wrestlers in the Sekitori division had
significantly larger fat-free mass index scores in comparison with wrestlers from
the lower divisions who share a common area of the chart. The cut-off point of
fat-free mass index which divided Sekitori wrestlers from other wrestlers is
approximately 30 and this value may be one of the anthropometrical indications of
whether or not a Sumo wrestler is destined to be successful.
PMID- 10195656
TI - Study of growth in rural school children from Buenos Aires, Argentina using upper
arm muscle area by height and other anthropometric dimensions of body
composition.
AB - The primary objective was to compare growth and body composition in an infantile
rural population by means of the upper arm muscle area by height and other
antropometric measurements. Research was carried out by way of a cross sectional
study, including 80% (321 6-13 year olds) of the schoolchildren living in General
Lavalle, a rural community of about 3000 inhabitants. The methods and procedures
included the evaluation of mother's educational levels and anthropometric
measurements. Height (H), weight, mid upper arm circumference, and triceps
skinfold (TS) were measured. The body mass index (BMI), the upper arm muscle area
(UAMA), the upper arm fat area (UAFA) and the upper arm muscle area by height
(UAMAH) were calculated. Variables were grouped by gender and age and transformed
into z-scores, using the US anthropometric standards as reference. The results
showed that: (1) the mother educational status was, in relation to z-scores, as
in an urban population, and (2) the z-scores for BMI, UAFA and TS were above the
reference, while the ones for H, UAMA and UAMAH were below the reference. The
differences between z-scores in relation to mother's educational levels were
statistically significant (p < 0.05). UAMA was correlated strongly with H (r =
0.67). The children of General Lavalle tend to be fatty and overweight, while
their muscle mass and H are proportionally low, but with values within the
reference. Thus, low muscle mass and H are, in general terms, indicative of low
protein reserves, the systematically low-anthropometry found for UAMAH suggests
that this index should be used in conjunction with other indexes (e.g. BMI, UAFA)
to obtain a more complete assessment of body composition and nutritional status.
PMID- 10195657
TI - Traditional reviews, meta-analyses and pooled analyses in epidemiology.
AB - BACKGROUND: The use of review articles and meta-analysis has become an important
part of epidemiological research, mainly for reconciling previously conducted
studies that have inconsistent results. Numerous methodologic issues particularly
with respect to biases and the use of meta-analysis are still controversial.
METHODS: Four methods summarizing data from epidemiological studies are
described. The rationale for meta-analysis and the statistical methods used are
outlined. The strengths and limitations of these methods are compared
particularly with respect to their ability to investigate heterogeneity between
studies and to provide quantitative risk estimation. RESULTS: Meta-analyses from
published data are in general insufficient to calculate a pooled estimate since
published estimates are based on heterogeneous populations, different study
designs and mainly different statistical models. More reliable results can be
expected if individual data are available for a pooled analysis, although some
heterogeneity still remains. Large prospective planned meta-analysis of
multicentre studies would be preferable to investigate small risk factors,
however this type of meta-analysis is expensive and time-consuming. CONCLUSION:
For a full assessment of risk factors with a high prevalence in the general
population, pooling of data will become increasingly important. Future research
needs to focus on the deficiencies of review methods, in particular, the errors
and biases that can be produced when studies are combined that have used
different designs, methods and analytic models.
PMID- 10195658
TI - Evaluation designs for adequacy, plausibility and probability of public health
programme performance and impact.
AB - The question of why to evaluate a programme is seldom discussed in the
literature. The present paper argues that the answer to this question is
essential for choosing an appropriate evaluation design. The discussion is
centered on summative evaluations of large-scale programme effectiveness, drawing
upon examples from the fields of health and nutrition but the findings may be
applicable to other subject areas. The main objective of an evaluation is to
influence decisions. How complex and precise the evaluation must be depends on
who the decision maker is and on what types of decisions will be taken as a
consequence of the findings. Different decision makers demand not only different
types of information but also vary in their requirements of how informative and
precise the findings must be. Both complex and simple evaluations, however,
should be equally rigorous in relating the design to the decisions. Based on the
types of decisions that may be taken, a framework is proposed for deciding upon
appropriate evaluation designs. Its first axis concerns the indicators of
interest, whether these refer to provision or utilization of services, coverage
or impact measures. The second axis refers to the type of inference to be made,
whether this is a statement of adequacy, plausibility or probability. In addition
to the above framework, other factors affect the choice of an evaluation design,
including the efficacy of the intervention, the field of knowledge, timing and
costs. Regarding the latter, decision makers should be made aware that evaluation
costs increase rapidly with complexity so that often a compromise must be
reached. Examples are given of how to use the two classification axes, as well as
these additional factors, for helping decision makers and evaluators translate
the need for evaluation--the why--into the appropriate design--the how.
PMID- 10195659
TI - Cancer mortality in Russia and Ukraine: validity, competing risks and cohort
effects.
AB - BACKGROUND: The dramatic increase in mortality in Russia and Ukraine in the late
1980s and 1990s has been due to increases in certain causes of death,
particularly cardiovascular disease and accidents and violence. In contrast,
there has been a slight fall in mortality from cancer. METHODS: This paper
presents an analysis of trends and patterns in cancer mortality and examines four
possible explanations for its recent fall: changes in data collection; cohort
effects; competing mortality from other causes of death; and improvements in
health care. RESULTS: All contribute to some extent to the observed changes, with
each affecting predominantly different age groups. There is evidence of a
significant underrecording of cancer deaths among the elderly especially in rural
areas and of significant changes in coding practices in the early 1990s.
Competing mortality from cardiovascular diseases and accidents can explain some
reduction in male deaths from cancer in middle age. Birth cohort effects can
explain some reduction among males after early middle age and among females at
all ages. The impact of changes in health care are more difficult to identify
with certainty but there is evidence of reduced deaths from childhood leukaemia.
IMPLICATIONS: Recent changes in mortality in Russia are complex and their
understanding will require a multidisciplinary approach embracing demography,
epidemiology and health services research.
PMID- 10195660
TI - Alcohol consumption as a major risk factor for the rise in liver cancer mortality
rates in Japanese men.
AB - BACKGROUND: Age-adjusted liver cancer mortality rates have been increasing for
both men and women in Japan since 1970; however, increases in mortality rates in
men are much greater than those in women. Hepatitis C virus infections and heavy
alcohol consumption are considered to be the major risk factors of liver cancer
deaths in Japanese. The purpose of this study is (1) to examine the pattern of
liver cancer mortality by gender and birth year to compare those with the pattern
of other alcohol-related mortality and (2) to estimate the attributable risk per
cent of heavy alcohol consumption for liver cancer deaths in Japanese men.
METHODS: Age-specific liver cancer mortality rates by gender were compared with
those of cirrhosis mortality rates. Then male-to-female mortality rate ratios
were calculated by birth cohort and compared with cirrhosis mortality rate ratios
and oesophageal cancer mortality rate ratios. The attributable risk per cent of
alcohol consumption for liver cancer death was calculated, using female liver
cancer mortality rates as standard rates. RESULTS: Examination of both gender and
birth cohort mortality rates revealed that male-to-female liver cancer mortality
rate ratios by birth cohort correspond well with those rate ratios for liver
cirrhosis and oesophageal cancer mortality. The attributable risk per cent of
alcohol consumption for liver cancer deaths in Japanese men was 70%. CONCLUSION:
Alcohol consumption is more important than hepatitis C virus infections as a
major cause of liver cancer deaths in Japanese men.
PMID- 10195661
TI - A mobile unit: an effective service for cervical cancer screening among rural
Thai women.
AB - BACKGROUND: We carried out a systematic screening programme using a mobile unit
with the purpose of increasing use of Papanicolaou (Pap) smear screening among
rural Thai women. The mobile unit campaign was carried out initially between
January and February 1993 and then in 1996 in all the 54 rural villages in Mae
Sot District, Tak Province, northern Thailand. METHODS: To evaluate the effect of
the programme on changes in knowledge and use of screening, we compared the
results of three interview surveys of women, 18-65 years old, in villages
selected by systematic sampling for each survey; first in 1991 (before the
operation of the programme), secondly in 1994 (one year after the first screening
campaign), and last in 1997 (one year after the second campaign). This report
also compares data on Pap smears taken by the mobile unit with other existing
screening services in the study area. RESULTS: A total of 1603, 1369, and 1576
women respectively, participated in each survey. The proportion of women reported
knowing of the Pap smear test increased from 20.8% in 1991 to 57.3% in 1994 and
to 75.5% in 1997. The proportion of women who had ever had a Pap smear increased
from 19.9% in 1991 to 58.1% in 1994 and to 70.1% by 1997. Screening by the mobile
unit accounted for 85.2% of all cervical intraepithelial neoplasia (CIN) III and
all invasive cancers identified among the Pap smears taken by screening services
in the area between 1992 and 1996. The rate of CIN III was 3.5/1000 smears in
this screening programme, which was 5.2 and 2.0 times higher than the rates in
the maternal and child health/family planning clinic and the annual one-week mass
screening campaign respectively. CONCLUSIONS: The use of a mobile unit may be an
effective screening programme in rural areas where existing screening activities
cannot effectively reach the female population at risk.
PMID- 10195662
TI - Trends in mortality from cutaneous malignant melanoma in Belgium.
AB - BACKGROUND AND METHODS: Changes over time of mortality rates from cutaneous
malignant melanoma (CMM) in Belgium were analysed, based on people (n = 3695)
aged 25-84 years, who died of CMM from 1954 to 1992. All data were collected from
the Belgian National Institute of Statistics. For the log-linear analysis and
calculation of the average annual change, only the data from 1973 to 1992 were
considered. RESULTS: The age-adjusted mortality rates (per 10(5)) for the age
group 25-84 years old increased from 0.5 in 1954 to 3.0 in 1992 in men, and from
0.8 in 1954 to 2.2 in 1992 in women. The average annual percentage change in men
(-0.003%) was stable over the period 1973-1982, and increased to 4.4% over the
period 1983-1992. In women, the average annual increase was 4.6% over the period
1973-1982, and continued to increase to 6.8% over the period 1983-1992. Log
linear analysis showed that the change in rates for both men and women was mainly
due to an age-'drift' effect, contrary to the results of the average annual
percentage change in men. CONCLUSION: The risk of dying from CMM increased in men
and women continuously over the whole period, irrespective of birth cohort. In
both men and women, there was approximately a 20% increase in CMM mortality per 5
year period.
PMID- 10195663
TI - Socioeconomic status and cardiovascular risk factors in the Czech Republic.
AB - BACKGROUND: In western countries, prevalence of cardiovascular diseases and most
risk factors is higher in lower socioeconomic groups. The social gradients in the
former communist societies are less well known. Because in western countries
different indicators of socioeconomic status (SES) are correlated, this gradient
is found with a number of different measures of SES. We have analysed the
presence and magnitude of the socioeconomic gradient in cardiovascular risk
factors in a former communist country. As the relationship between material
conditions and education has been much weaker than in the west, we have also
attempted to separate their effects. METHODS: A cross-sectional survey examined a
random sample of men and women resident in six Czech districts participating in
the MONICA study in 1992. Participants completed a questionnaire, underwent
anthropometric and blood pressure measurements, and provided a blood sample. Two
indicators of SES were used: education and material conditions, the indicator
constructed from car ownership and crowding. Linear regression was employed to
analyse the relation between SES and total and high-density lipoprotein (HDL)
cholesterol, body mass index (BMI), waist-hip ratio (WHR) and height. Logistic
regression was used to assess the association between SES and smoking and
hypertension. RESULTS: A total of 1141 men and 1212 women (overall response rate
75%) participated in the study. After controlling for age, all risk factors were
associated with education, except HDL cholesterol in women and BMI in men; only
smoking in both sexes and WHR in women and height in men were significantly
related to material conditions. In mutually adjusted analyses, educational
gradients persisted but associations with material conditions disappeared or
became substantially weaker. The magnitude of the educational differences was
similar to those found in western countries. CONCLUSIONS: Socioeconomic
differences in cardiovascular risk factors in Czech Republic in 1992 had the same
direction and similar magnitude as in Western Europe, and were strongly related
to education rather than material conditions. Materialist explanations for the
social differences seem unlikely in this population.
PMID- 10195664
TI - Physical activity assessment in population surveys: can it really be simplified?
AB - BACKGROUND: Several studies have used a simplified approach for the assessment of
physical activity such as the frequency of exercise-induced sweating. In this
study leisure-time physical activity has been assessed using this and another
more detailed measure. SUBJECTS AND METHODS: A sample of 4171 adults answered the
Health Interview Survey of Barcelona in 1992. The respondents were classified
into categories depending on participation in moderate and/or intense physical
activity (> or =20 min) and also according to the frequency of exercise-induced
sweating: 0, 1-2 and > or =3 times/week. Agreement between the two measures was
calculated using the weighted Kappa (Kw) statistic with 95% confidence intervals
(95% CI). Stratified analyses were performed. RESULTS: Prevalence of physical
activity > or =3 times/week was lower with the sweat question (12.5%) than with
the questions about the frequency of performance of selected activities (19.6%).
The physical activity patterns by age, gender and overweight were similar for the
two measures, but differed by month of the year. Agreement was lower among the
older age categories and was higher among males (Kw = 0.59, 95% CI: 0.57-0.62)
than among females (Kw = 0.48, 95% CI: 0.46-0.50). Overall, the agreement was
higher in the hotter months (Kw = 0.72 among males and 0.58 among females).
CONCLUSIONS: In the assessment of physical activity in the population by means of
the sweat question there can be interference from other variables, apart from the
intensity of the activity, which influence sweating during the exercise. Further
assessments of the validity of exercise-induced sweating in representative
samples of the general population would be useful.
PMID- 10195665
TI - Inequalities in mortality according to educational level in two large Southern
European cities.
AB - BACKGROUND: In Spain, studies on social inequalities in mortality based on
individuals are few due to the poor quality of information on occupation in death
certificates. This study looks at the differences in mortality according to
educational level, using individual information obtained through the linkage
between the Death Register and the Municipal Census, in the cities of Madrid and
Barcelona, Spain. METHODS: The study populations were residents of Madrid and
Barcelona aged >24 years, who died in 1993 and 1994. Indicators obtained for each
city and educational level were: age- and sex-specific mortality rates, and life
expectancy at 25 years. Poisson regression models were fitted to obtain the
relative risk (RR) of death for each educational level with respect to the
reference level (higher education completed), adjusted for age. RESULTS: The
mortality rate was lower among individuals with higher educational levels, while
life expectancy at 25 years was higher. In both cities men and women with no
education showed the highest mortality in all age groups, with very high RR in
the youngest age group (RR for men aged 25-34 years = 7.08 in Madrid and 6.02 in
Barcelona, whereas in women these RR were 6.33 and 5.63 respectively). In
Barcelona the greater part of the overall mortality difference for the group aged
25-34 years was due to AIDS (acquired deficiency syndrome, 33.4% in men and 59.3%
in women). CONCLUSION: The present study has found higher mortality (mainly from
AIDS) among individuals with no academic qualifications thus drawing attention to
the need to implement policies aimed at reducing these inequalities.
PMID- 10195666
TI - Classification differences and maternal mortality: a European study. MOMS Group.
MOthers' Mortality and Severe morbidity.
AB - OBJECTIVES: To compare the ways maternal deaths are classified in national
statistical offices in Europe and to evaluate the ways classification affects
published rates. METHODS: Data on pregnancy-associated deaths were collected in
13 European countries. Cases were classified by a European panel of experts into
obstetric or non-obstetric causes. An ICD-9 code (International Classification of
Diseases) was attributed to each case. These were compared to the codes given in
each country. Correction indices were calculated, giving new estimates of
maternal mortality rates. SUBJECTS: There were sufficient data to complete
reclassification of 359 or 82% of the 437 cases for which data were collected.
RESULTS: Compared with the statistical offices, the European panel attributed
more deaths to obstetric causes. The overall number of deaths attributed to
obstetric causes increased from 229 to 260. This change was substantial in three
countries (P < 0.05) where statistical offices appeared to attribute fewer deaths
to obstetric causes. In the other countries, no differences were detected.
According to official published data, the aggregated maternal mortality rate for
participating countries was 7.7 per 100,000 live births, but it increased to 8.7
after classification by the European panel (P < 0.001). CONCLUSION: The
classification of pregnancy-associated deaths differs between European countries.
These differences in coding contribute to variations in the reported numbers of
maternal deaths and consequently affect maternal mortality rates. Differences in
classification of death must be taken into account when comparing maternal
mortality rates, as well as differences in obstetric care, underreporting of
maternal deaths and other factors such as the age distribution of mothers.
PMID- 10195667
TI - Maternal mortality in Guinea-Bissau: the use of verbal autopsy in a multi-ethnic
population.
AB - BACKGROUND: In developing countries with scanty resources it is very important to
have reliable data to establish priorities for the health sector; e.g. to reduce
maternal mortality it is necessary to determine the most important causes. The
majority of deaths, however, occur without previous contact with the health
system and consequently conventional analyses of death certificates are not
feasible. Instead, studies have been carried out in some developing countries
with various forms of post-mortem interviews, the so-called verbal autopsies
(VA). METHODS: We developed a structured interview with filter questions, which
was applied to all deaths of women of fertile age in a cohort of 10,000 women
living in 100 clusters in Guinea-Bissau and followed over a period of 6 years.
The cause of death was ascertained by means of a series of diagnostic algorithms
for the most common causes of maternal mortality, including postpartum
haemorrhage, antepartum haemorrhage, puerperal infection, obstructed labour,
eclampsia, abortion, and ectopic pregnancy. RESULTS: Of the 350 deaths of women
of fertile age, 32% were maternal and it seems unlikely that a significant
proportion of maternal deaths have not been classified correctly. Using the
diagnostic algorithm 70% could be given a specific diagnosis, the most important
causes being postpartum haemorrhage (42% [29/69]), obstructed labour (19%
[13/69]), and puerperal infection (16% [11/69]). We attempted to identify the
factors that are critical for obtaining sufficient information to reach a
diagnosis. In the univariate analyses, it was important whether the respondent
had been present during the last illness (P = 0.04) and whether the death
occurred more than one week after delivery (P = 0.04). The husband was a better
respondent than a co-wife (P = 0.08), and men in general provided more specific
information than women (P = 0.08). Furthermore, information appeared to be better
if the woman had died in the rainy season (P = 0.08). The length of the recall
period, parity, age of woman, place of death, rural/urban residence, and ethnic
group were not decisive. In the multivariate analysis sex and presence of
respondent and time after delivery were significantly associated with the risk of
not reaching a specific diagnosis. Women are less likely to provide adequate
information for a diagnosis than men (odds ratio [OR] 3.1; 95% confidence
interval [CI]: 1.2-8.1). Respondents that did not reside in the village during
the departed woman's illness/delivery carried equal risk of not reaching a
conclusion (OR 3.1; CI: 1.1-9.1). Deaths occurring more than one week after
delivery were also less likely to be classified (OR 6.1; CI: 1.7-22.0).
CONCLUSION: The VA described in the present paper left 30% of the maternal deaths
unclassified without a specific diagnosis. Had all interviews been with husbands,
only 14% would have remained unclassified. If we had only asked people who were
present during the terminal phase of the victim's illness the proportion of
classified deaths would have risen from 70% to 75%. It is likely that delayed
maternal deaths have not been adequately covered by the present algorithms, but
they may also simply be more difficult to describe due to the duration of the
disease episode. In contrast to methods by which cause of death is established by
a panel of medical experts, the present VA should be economically and technically
viable in areas where health workers have only minimal training.
PMID- 10195668
TI - The effects of wine and tobacco consumption on cognitive performance in the
elderly: a longitudinal study of relative risk.
AB - BACKGROUND: Evidence relating to the potentially protective effect of smoking and
alcohol consumption in relation to senescent cognitive decline and Alzheimer's
disease is inconclusive. METHODS: The relationship between wine and tobacco
consumption and cognitive change was assessed within a longitudinal study of
normal elderly people showing recent instability in cognitive functioning using
an extensive battery of cognitive tests. RESULTS: While moderate wine consumption
was found to be associated with a fourfold diminishing of the risk of Alzheimer's
disease (OR = 0.26), as found in other studies, this effect was found to
disappear when institutionalization was taken into account. Wine consumption was
associated with an increased risk of decline over time in attention and in
secondary memory. No protective effect for Alzheimer's disease was found for
smoking, although smoking was associated with a decreased risk for decline over
time in attentional and visuospatial functioning. No clear combined effect of
smoking and drinking was found, even though smoking was found to increase the
risk of decline in language performance when adjusted on wine consumption.
CONCLUSIONS: There is no evidence to suggest that wine and tobacco consumption
may protect against Alzheimer's disease.
PMID- 10195669
TI - The comparison of mixed distribution analysis with a three-criteria model as a
method for estimating the prevalence of iron deficiency anaemia in Costa Rican
children aged 12-23 months.
AB - BACKGROUND: A maximum likelihood method of mixed distribution analysis (MDA) is
presented as a method to estimate the prevalence of iron deficiency anaemia (IDA)
in Costa Rican infants 12-23 months old. MDA characterizes the parameters of the
admixed distributions of iron deficient anaemics and non-iron-deficient-anaemics
(NA) from the frequency distribution of haemoglobin concentration of the total
sample population. METHODS: Data collected by Lozoff et al. (1986) from 345 Costa
Rican infants 12-23 months old were used to estimate the parameters of the IDA
and NA haemoglobin distributions determined by MDA and the widely used three
criteria model of iron deficiency. The estimates of the prevalence of IDA by each
of the methods were compared. The sensitivity and specificity of MDA compared to
diagnosis by the three-criteria method were assessed. Simulations were carried
out to assess the comparability of MDA and the three-criteria method in low and
high prevalence scenarios. RESULTS: The mean and standard deviation (SD) of the
NA haemoglobin distribution determined by both methods was 12.1 +/- 1.0 g/dL. The
IDA haemoglobin distribution determined by MDA had a mean and SD of 10.2 +/- 1.3
g/dL while the IDA distribution by the three-criteria method had a mean and SD of
10.4 +/- 1.3 g/dL. The prevalences of IDA as estimated by MDA and the three
criteria method were 24% and 29%, respectively. The sensitivity and specificity
of MDA were 95% and 97%, respectively. The performance of MDA was similar to the
three-criteria method at a simulated high prevalence of IDA and less similar at a
low prevalence of IDA. CONCLUSIONS: Compared to the reference three-criteria
method MDA provides a more accurate estimate of the true prevalence of IDA than
the haemoglobin cutoff method in a population of children aged 12-23 months with
a moderate to high prevalence of IDA. MDA is a less costly method for estimating
the severity of IDA in populations with moderate to high prevalences of IDA, and
for assisting in the design, monitoring and evaluation of iron intervention
programmes.
PMID- 10195670
TI - Poverty area residence and changes in depression and perceived health status:
evidence from the Alameda County Study.
AB - BACKGROUND: Previous evidence from the Alameda County Study indicated that
residential area has an independent effect on risk for mortality, adjusting for a
variety of important individual characteristics. The current research examined
the effect of poverty area residence on risk for developing depressive symptoms
and decline in perceived health status in a sample of 1737. METHODS: Data were
from a longitudinal population-based cohort. Multiple logistic regression
analyses were used. RESULTS: Age- and sex-adjusted risk for incident high levels
of depressive symptoms in 1974 was higher for poverty area residents (odds ratio
[OR] 2.14; confidence interval [CI]: 1.49-3.06). Those reporting excellent/good
health in 1965 were at higher risk for having fair/poor health in 1974 if they
lived in a poverty area (age- and sex-adjusted OR 3.30; CI: 2.32-4.71).
Independent of individual income, education, smoking status, body mass index, and
alcohol consumption, poverty area residence remained associated with change in
outcome variables. CONCLUSION: These results further support the hypothesis that
characteristics of place affect health conditions and health status.
PMID- 10195671
TI - Unemployment pre-dates symptoms of depression and anxiety resulting in medical
consultation in young men.
AB - BACKGROUND: There is evidence to support a link between unemployment and lower
levels of psychological well-being, but debate continues as to whether
unemployment results in psychological morbidity, or whether the association is
due to those who are more vulnerable to mental illness becoming unemployed. Here
we assess the effect of recent and accumulated unemployment in young men on the
risk of developing depression and anxiety leading to medical consultation.
Adjustment was made for a measure of pre-existing tendency to depression,
behavioural maladjustment, social class, qualifications and region of residence.
METHODS: Some 3241 men from the National Child Development Study (the 1958
British birth cohort) with data from birth to age 33 years, collected at birth
and ages 7, 11, 16, 23 and 33 years were used in these analyses. The outcome
measure was onset age of anxiety or depression between ages 24 and 33 years, that
resulted in consultation with a GP or a specialist. This was used in Cox
proportional hazards models where two measures of unemployment were modelled as
time varying covariates. Pre-existing tendency to depression was measured by the
Malaise Inventory prior to the experience of unemployment at age 23 years. Two
measures of unemployment were investigated: any unemployment in the year prior to
onset (recent unemployment) and all accumulated unemployment prior to onset
(divided into four categories: 0, 1-12, 13-36 and 37+ months of unemployment).
RESULTS: After adjustment for potential confounding factors including pre
existing tendency to depression, the relative risk (RR) for developing symptoms
resulting in consultation was 2.10 (95% CI: 1.21-3.63), when those who were
unemployed in the year prior to onset were compared with those who were not.
Accumulated unemployment was not statistically significantly related to onset of
symptoms in all men after adjustment for the potential confounding factors: an RR
of 1.63 (95% CI: 0.95-2.79) for men with 37+ months of accumulated unemployment
when compared with none. However, exclusion of men with a pre-existing tendency
to depression indicated by the Malaise Inventory score, increased the RR to 2.30
(95% CI: 1.44-3.65) for recent unemployment and 2.04 (95% CI: 1.17-3.54) for 37+
months of accumulated unemployment when compared with none. CONCLUSIONS:
Unemployment is a risk factor for psychological symptoms of depression requiring
medical attention, even in those men without previous psychological
vulnerability.
PMID- 10195672
TI - Health service accessibility and deaths from asthma.
AB - BACKGROUND: Good access to health services may be important for effective asthma
management amongst patients, thus preventing unnecessary deaths. In a previous
study, we found elevated levels of asthma mortality in English local authority
districts with poor access to acute hospitals. Here, the relationship between
asthma mortality and access to primary and secondary services within the rural
region of East Anglia is examined. METHODS: A geographically based descriptive
study, within 536 electoral wards in the region of East Anglia, England.
Regression analysis was used to examine the relationship between health service
accessibility, and mortality from asthma during the period January 1985 to
December 1995. RESULTS: After controlling for confounding factors, there was a
significant tendency for asthma mortality to increase with travel time to
hospital, with a relative risk of 1.07 for each 10-minute increase in journey
time (P = 0.04). There was no consistent trend for mortality to increase with
travel time to general practitioner surgeries. CONCLUSIONS: The results of this
study support the conclusions of earlier work that inaccessibility of acute
hospital services may increase the risk of asthma mortality. The provision of
good access to these facilities may be one factor in reducing the burden of
avoidable deaths from asthma.
PMID- 10195673
TI - Investigation of under-ascertainment in epidemiological studies based in general
practice.
AB - BACKGROUND: One of the aims of the Study of Infectious Intestinal Disease (IID)
in England is to estimate the incidence of IID presenting to general practice.
This sub-study aims to estimate and correct the degree of under-ascertainment in
the national study. METHODS: Cases of presumed IID which presented to general
practice in the national study had been ascertained by their GP. In 26 general
practices, cases with computerized diagnoses suggestive of IID were identified
retrospectively. Cases which fulfilled the case definition of IID and should have
been ascertained to the coordinating centre but were not, represented the under
ascertainment. Logistic regression modelling was used to identify independent
factors which influenced under-ascertainment. RESULTS: The records of 2021
patients were examined, 1514 were eligible and should have been ascertained but
only 974 (64%) were. There was variation in ascertainment between the practices
(30% to 93%). Patient-related factors independently associated with ascertainment
were: i) vomiting only as opposed to diarrhoea with and without vomiting (OR
0.37) and ii) consultation in the surgery as opposed to at home (OR 2.18).
Practice-related factors independently associated with ascertainment were: i)
participation in the enumeration study component (OR 1.78), ii) a larger number
of partners (OR 0.3 for 7-8 partners); iii) rural location (OR 2.27) and iv)
previous research experience (OR 1.92). Predicted ascertainment percentages were
calculated according to practice characteristics. CONCLUSION: Under-ascertainment
of IID was substantial (36%) and non-random and had to be corrected. Practice
characteristics influencing variation in ascertainment were identified and a
multivariate model developed to identify adjustment factors which could be
applied to individual practices. Researchers need to be aware of factors which
influence ascertainment in acute epidemiological studies based in general
practice.
PMID- 10195674
TI - Capture-recapture method for estimating misclassification errors: application to
the measurement of vaccine efficacy in randomized controlled trials.
AB - BACKGROUND: The measure of efficacy is optimally performed by randomized
controlled trials. However, low specificity of the judgement criteria is known to
bias toward lower estimation, while low sensitivity increases the required sample
size. A common technique for ensuring good specificity without a drop in
sensitivity is to use several diagnostic tests in parallel, with each of them
being specific. This approach is similar to the more general situation of case
counting from multiple data sources, and this paper explores the application of
the capture-recapture method for the analysis of the estimates of efficacy.
METHOD: An illustration of this application is derived from a study on the
efficacy of pertussis vaccines where the outcome was based on > or =21 days of
cough confirmed by at least one of three criteria performed independently for
each subject: bacteriology, serology, or epidemiological link. Log-linear methods
were applied to these data considered as three sources of information. RESULTS:
The best model considered the three simple effects and an interaction term
between bacteriology and epidemiological linkage. Among the 801 children
experiencing > or =21 days of cough, it was estimated that 93 cases were missed,
leading to a corrected total of 413 confirmed cases. The relative vaccine
efficacy estimated from the same model was 1.50 (95% confidence interval: 1.24
1.82), similar to the crude estimate of 1.59 and confirming better protection
afforded by one of the two vaccines. CONCLUSION: This method allows supporting
analysis to interpret primary estimates of vaccine efficacy.
PMID- 10195675
TI - Estimation of injecting drug users in the City of Edinburgh, Scotland, and number
infected with human immunodeficiency virus.
AB - OBJECTIVES: To estimate (1) the number of current and former injecting drug users
(IDU) infected with human immunodeficiency virus (HIV) alive in Edinburgh, and
(2) the total number of current injectors in the city. METHODS: The number of
infected IDU was estimated using a local register of HIV infections with
correction for incompleteness of the register. The number of injectors was
estimated by two independent methods, one based on the HIV register, the other by
log-linear modelling of four lists of IDU interviewed in a city-wide survey,
and/or attending drug treatment agencies and family doctors because of drug use.
MAIN OUTCOME MEASURES: Estimates for the period 1992-1994 of number of IDU
infected with HIV, total number of IDU, and prevalence of injecting. RESULTS: The
HIV register indicated that 371 infected drug users who had ever injected were
alive and resident in Edinburgh. In all, 95% of infected survey respondents
appeared in the register, leading to a corrected estimate of 472 infected ever
injectors. From this the number of IDU currently injecting (i.e. in the previous
6 months) was estimated to be 1770 (95% CI: 1340-2240), and the prevalence of
injecting as 8.0 (95% CI: 4.8-10.8) per 1000 Edinburgh residents aged 15-59
years. Log-linear modelling gave an estimate of 2070 (95% CI: 1360-2800) current
injectors. CONCLUSIONS: The number of HIV-infected IDU in Edinburgh was estimated
to be twice that in the larger nearby city of Glasgow, where a higher proportion
of young adults currently injected drugs. Knowledge of the high prevalence of HIV
in Edinburgh IDU (19.3%), the prescribing of oral substitutes, and counselling by
doctors and drug workers are perceived reasons for the reduction in the
prevalence of injecting which has occurred in Edinburgh in recent years. Such
measures need to be continued to encourage further reduction of injecting.
PMID- 10195676
TI - Reconstruction of human immunodeficiency virus (HIV) sub-epidemics in Italian
regions.
AB - BACKGROUND: The spread of human immunodeficiency virus (HIV) infections is likely
to consist of sub-epidemics in local areas and/or risk groups. Small-area risk
group specific analyses may thus be a suitable means of better understanding and
controlling the epidemic course. METHODS: An age, period, and cohort back
calculation method was used to reconstruct region-specific epidemics of HIV
infection. The HIV infection incidence rates were estimated for individual
Italian regions by using as denominator the specific risk category population
(i.e. intravenous drug user population [IDU], homosexual/ bisexual population
[MSWM], and Italian general population for heterosexual contacts [HST]).
Incidence rates obtained in this way represent the risk of HIV infection
conditional to belonging to the specific sub-group of the population. RESULTS:
The HIV epidemic is heterogeneous in terms of gender, risk category and region.
The highest risk of HIV infection has been estimated in the Lombardia region
(North-West area) among men belonging to the IDU category in 1985. In recent
years, a trend of decrease in HIV has been estimated, especially among IDU and
MSWM. For the HST category, some regions have shown trends of great increase,
particularly on the island of Sardegna and the regions of Puglia and Sicilia
(Southern Italy). In 1987, most HIV infections were observed among IDU (39-90%),
while in 1992 the MSWM and HST categories made the greatest contribution to the
HIV epidemic. CONCLUSIONS: The results stress the idea of sub-epidemics rather
than a single epidemic affecting the entire country. Some Southern regions emerge
as areas in which the spread of HIV infections, although still at a rather low
level, should cause considerable concern, particularly the trend of new
infections by heterosexual transmission involving the general population.
Detailed information on levels and trends of HIV infection epidemics at the local
level are essential for surveillance purposes and for planning health care
facilities, and can highlight areas in which preventive measures can be
effective.
PMID- 10195677
TI - Incidence rate of Creutzfeldt-Jakob disease in Japan.
AB - BACKGROUND: The objective of this study is to clarify the incidence rate of
Creutzfeldt-Jakob disease (CJD) during the last decade in Japan. METHODS: A
nationwide mail survey was conducted in all hospitals with a minimum bed capacity
of 100 and having at least one of three departments: neurology, psychiatry, and
neuropathology. The survey required the patient's sex, date of birth, date of
diagnosis, diagnostic criteria, medical history and CJD incidence in the family.
RESULTS: From 493 hospitals throughout the country, 821 patients with CJD were
reported from January 1985 through March 1996. The annual incidence rate was 0.49
per million population for males and 0.68 for females. The age-specific incidence
rate was highest among those 70-79 years of age, followed by the 60-69, and 50-59
age groups. The incidence and mortality increased during the observed period;
however, the incidence rate among younger generations did not rise. CONCLUSION: A
nationwide incidence survey of CJD in Japan revealed the incidence and
distribution of the disease over the recent decade. It was found that the
incidence and mortality rates had increased during the observed period.
PMID- 10195678
TI - Tuberculosis epidemiology and control in Veracruz, Mexico.
AB - BACKGROUND: Tuberculosis (TB) rates remain high in regions of Southern Mexico
despite the existence of a National Tuberculosis Program. Understanding TB
epidemiology in such settings would assist in the design of improved TB control
and highlight the challenges confronting TB control in developing countries.
METHODS: We conducted a retrospective review of treatment control cards from 1991
to 1994 in five municipalities in a semiurban region of Southern Mexico. RESULTS:
The relatively high rate of TB observed, 42.6 per 100,000 inhabitants, did not
change significantly during the study period. Cure rates among new cases were 79%
and significantly lower among retreatment cases (62%). Directly observed therapy
(DOT) was administered to 84% of patients. Approximately one-half of the
retreatment cases who were not cured were compliant with therapy, suggesting that
drug resistance contributed to these poor results. Of particular concern was a
core group of 16 patients who had received at least three treatments.
CONCLUSIONS: This region of Mexico has persistently high TB rates despite a DOT
based TB control programme which achieves an overall cure rate of 77%. There
exist many retreatment cases for whom cure rates are significantly lower. These
cases may serve as a core group for the dissemination of drug resistant TB. The
control programme is being reinforced by a nominal register of patients,
decreasing administrative barriers for drug supply to individual patients and the
availability of mycobacteria cultures. In addition to these measures, in regions
which are approaching the levels of efficacy recommended by the WHO it may be
appropriate to consider focusing efforts on the identification and treatment of
chronic cases.
PMID- 10195679
TI - Measles in adults in Canada and the United States: implications for measles
elimination and eradication.
AB - BACKGROUND: Despite the implementation of mass school catch-up campaigns for
measles in Canada, an outbreak of measles occurred in early 1997 mostly affecting
the adult population. The higher incidence in Canada in adults led us to compare
immunization policies and the evolution of measles among adults in Canada and the
US. METHODS: Based on information gathered from both national immunization
programmes and surveillance systems. RESULTS: Although the proportion of cases
occurring in adults has increased tremendously in both countries in the past
decade, there was no increase in measles incidence in these populations. The most
likely factors to explain the higher rate of measles occurring in adults in
Canada are the younger age at administration of first dose in Canada, the delay
in implementation of a second dose policy in Canada compared with the US combined
with the lack of prematriculation immunization requirements in Canadian colleges
and universities, and the higher rate of overseas travel to and from Canada. The
situation in Canada may also have been exacerbated by incomplete efforts to
control measles for many years without attempting to eliminate the disease.
CONCLUSIONS: In order to prevent measles in adults, high-risk groups must be
identified and catch-up for selected groups considered. Vaccination of
international travellers to endemic areas should be recommended until global
elimination has been achieved. Appropriate measles control strategies in younger
populations seem to be effective in preventing measles in adults. The experience
in Canada and the US suggests that measles transmission in adults is unlikely to
be a major impediment to regional elimination or global eradication.
PMID- 10195680
TI - Seroconversions in unvaccinated infants: further evidence for subclinical measles
from vaccine trials in Niakhar, Senegal.
AB - BACKGROUND: Increases in measles antibodies without rash-illnesses have been
documented in previously vaccinated children exposed to measles cases. The
phenomenon has been incompletely evaluated in young unvaccinated infants with
immunity of maternal origin. METHODS: Monthly cohorts of newborns were
prospectively randomized to vaccine and placebo control groups during a trial of
high-titre vaccines in Niakhar, Senegal. Measles antibodies were assayed in blood
samples of enrolled children collected at 5 months old, when controls received a
placebo injection, and at 10 months, when the placebo group was given measles
vaccine. Intensive prospective surveillance for measles was conducted throughout
the trial. RESULTS: One-fifth (n = 53) of the placebo controls seroconverted,
with known exposure to a measles case in only three of them. None of the
seroconverters developed a measles-like rash. Sixteen-fold or greater increases
in titres were noted in about one-quarter of them. Compared with placebo controls
who did not seroconvert, seroconverters were more likely to have had exposure to
a measles case and to travel, more likely to be boys than girls, and had
significantly lower baseline antibody titres. Measles was endemic in the study
area throughout the trial. Seroconversions did not adversely effect subsequent
nutritional indices or mortality. CONCLUSIONS: Although laboratory errors and
inadvertent injection of vaccine rather than placebo may have played some role,
they do not fully explain the above observations, which are consistent with
subclinical measles in the seroconverters. The possible role of subclinical
measles in occult transmission, its potential effect on the type and duration of
subsequent immunity, and its impact on response to primary vaccination need to be
determined.
PMID- 10195681
TI - Protective effect of breastfeeding: an ecologic study of Haemophilus influenzae
meningitis and breastfeeding in a Swedish population.
AB - BACKGROUND: In Orebro County, Sweden, a 2.5-fold increase in the incidence of
Haemophilus influenzae (HI) meningitis was found between 1970 and 1980. In a case
control study of possible risk factors for invasive HI infection conducted in the
same area, 1987-1992, breastfeeding was found to be a strong protective factor.
MATERIAL AND METHODS: In order to study the relation between incidence rates of
HI meningitis between 1956-1992 and breastfeeding rates in the population an
ecologic study was performed. RESULTS: A strong (negative) correlation between
breastfeeding and incidence of HI infection 5 to 10 years later (rho(xy) (s)
approximately -0.6) was seen, whereas no relation seems to exist for the time lag
15 years and beyond. The correlation for contemporary data was intermediate.
There were similar results for the breastfeeding proportions at 2, 4 as well as 6
months of age. DISCUSSION: Our ecologic data are consistent with results from our
case-control study. The time-lag for the delayed effect on the population level
could be estimated although sparse data make the estimates vulnerable to sampling
fluctuations. Limitations with ecologic studies are discussed. CONCLUSION: There
seems to be an association between high breastfeeding rate in the population and
a reduced incidence of HI meningitis 5 to 10 years later. These results do have
implications on strategies for breastfeeding promotion, especially in countries
where Hib vaccination is too costly and not yet implemented.
PMID- 10195682
TI - Risk factors for severe respiratory syncytial virus infection leading to hospital
admission in children in the Western Region of The Gambia.
AB - BACKGROUND: Acute lower respiratory tract infections (ALRI) are the major cause
of mortality and morbidity in young children worldwide. Respiratory syncytial
virus (RSV) infection is the most important viral cause of severe ALRI but only a
small proportion of children infected with this virus develop severe disease. To
identify possible risk factors for severe RSV infection leading to hospital
admission we have carried out a case-control study of Gambian children with RSV
infection admitted to hospital. METHODS: In all, 277 children admitted to three
hospitals in the Western Region of The Gambia with lower respiratory tract
infection due to RSV were compared with 364 control children matched for age and
location of residence who had not been admitted to hospital with an ALRI during
the RSV season. A detailed questionnaire covering a wide range of potential
social, environmental and nutritional risk factors was administered to the
child's guardian. RESULTS: Cases came from larger or more crowded compounds than
controls; increased risk was particularly associated with greater numbers of
children in the age group 3-5 years living in the compound (odds ratio [OR] for >
or =2 children in the age group 3-5 years = 9.1, 95% CI: 3.7-28). Cases were more
likely to have a sibling who had died (OR = 3.4, 95% CI: 1.7-7). Controls were
more likely to have been exposed to smoke from cooking fires (OR for the mother
of cases cooking at least once daily = 0.31, 95% CI: 0.14-0.7). Other protective
factors were father's nationality and some professions. Vegetables were included
in the diet of controls more frequently than in that of cases (OR = 0.16, 95% CI:
0.06-0.46). Mothers of cases complained of asthma more frequently than mothers of
controls, but the number of asthmatic mothers was small (4.2 versus 0.5%, P =
0.05). CONCLUSIONS: Risk factors for severe RSV infection identified in this
study are not amenable to public health interventions. Prevention of severe
infection is likely to require the development of an effective vaccine.
PMID- 10195683
TI - Dracunculiasis in Cameroon at the threshold of elimination.
AB - BACKGROUND: Dracunculiasis is endemic in Mayo Sava Division in the Far North
Province of Cameroon. Transmission occurs during the rainy season with a peak in
the months of July and August. METHODS: A combination of interventions consisting
of active surveillance, social mobilization, health education, distribution of
filters, construction of new water sources, chemical treatment of unsafe water
sources with temephos, and case containment were applied in Mayo Sava in 1990
1995 by the national Guinea Worm Elimination Programme (GWEP). Dracunculiasis
cases were detected by village health workers, confirmed by health outreach teams
and reported weekly to the GWEP. RESULTS: A decline in the incidence of
dracunculiasis by 98.1% from 778 cases in 1990 to 15 in 1995, and in the number
of endemic villages by 92.7% from 82 in 1990 to 6 in 1995 was achieved. The
proportion of cases identified < or =24 hours of worm emergence increased from
19% in 1991 to 73.6% in 1993. Over 1500 nylon monofilament filters were
distributed yearly to endemic villages lacking safe drinking water sources, while
81 new water sources were constructed (boreholes, wells and dikes), 55% in 1992
1993. The success of GWEP is attributed mainly to: intensive and simultaneous
implementation of interventions in highly endemic villages in the first 3 years
of the programme, case containment, and cash reward. CONCLUSIONS: Cameroon is on
the threshold of eliminating dracunculiasis from Mayo Sava but the major
remaining obstacle is the ever increasing threat of re-infestation from
neighbouring countries.
PMID- 10195684
TI - Nematode intestinal parasites of children in rural Guinea, Africa: prevalence and
relationship to geophagia.
AB - BACKGROUND: Intestinal parasitism is common among children in developing
countries, but the risk factors for infection are not well characterized.
METHODS: A stool examination was performed on 286 randomly selected children aged
1-18 years from three rural villages in Guinea, Africa. Information collected by
questionnaire was used to examine the relationship between geophagia and
infection with intestinal nematodes acquired by ingestion versus skin
penetration. RESULTS: Fifty-three per cent of children were infected by at least
one type of soil-transmitted nematode. Geophagia was reported by parents to occur
in 57%, 53%, and 43%, of children ages 1-5, 6-10, and 11-18 years, respectively.
The pattern of geophagia by age and gender of the children more closely resembled
the infection pattern for the two orally acquired and soil-transmitted nematodes
(Ascaris lumbricoides, Trichuris trichiura) than it did the infection pattern for
the two soil-transmitted nematodes that infect by skin penetration (hookworm,
Strongyloides stercoralis). CONCLUSIONS: These findings demonstrate that
geophagia is an important risk factor for orally acquired nematode infections in
African children. Education regarding geophagia prevention should be an integral
component of any soil-transmitted parasite control programme.
PMID- 10195685
TI - Estimation of prevalence proportion rates.
PMID- 10195686
TI - Insulin inhibition of glucocorticoid-stimulated gene transcription: requirement
for an insulin response element?
AB - The glucocorticoid hormone receptor binds to regulatory elements of target genes
and activates transcription through interactions with coactivators. For a subset
of genes, glucocorticoid receptor activity is inhibited by insulin. The present
paper analyzes recent data on the molecular mechanisms whereby insulin exerts
this antiglucocorticoid effect. Two models are proposed. In the first model
insulin controls the activity of an insulin-responsive factor bound to an insulin
responsive DNA element. In a second model, insulin targets a non-DNA bound
coactivator of the glucocorticoid receptor. Here, the gene-specificity of the
effect of insulin is conferred by the combined action of the glucocorticoid
receptor, of DNA-bound transcription factors and of coactivators, which form a
higher order structure that binds to a DNA sequence called glucocorticoid/insulin
responsive unit.
PMID- 10195687
TI - Treatment of human endometrial stromal cells with chorionic gonadotropin promotes
their morphological and functional differentiation into decidua.
AB - Human endometrial stromal cells contain luteinizing hormone (LH)/human chorionic
gonadotropin (hCG) receptors and treatment with highly purified hCG results in an
up-regulation of cyclooxygenase-2 (COX-2) gene expression and increased
production of prostaglandin (PG) E2. Since PGE2 promotes the differentiation of
endometrial stromal cells into decidua, we tested the hypothesis that LH and hCG
themselves may promote this process. The results revealed that these hormones can
promote morphological as well as functional differentiation. While their action
on morphological differentiation did not require the presence of estradiol (E2)
and progesterone (P4), they did require them for the functional differentiation.
The hCG effect was mimicked by LH, but not by follicle stimulating hormone (FSH),
thyroid stimulating hormone (TSH) or alpha and beta subunits of hCG, suggesting
that the hCG action was hormone specific and requires the conformation of native
hormone. The hCG treatment also increased the steady state PRL mRNA levels. This
increase was due to an increase in the transcription rate of the gene rather than
a decrease in the degradation of PRL transcripts. In summary, we conclude that
hCG and LH can increase the morphological as well as functional differentiation
of human endometrial stromal cells into decidua. This is one of the newly
discovered actions of LH and hCG that may be important for the implantation of
blastocyst and maintenance of pregnancy.
PMID- 10195688
TI - Regulation of human growth hormone receptor gene transcription by
triiodothyronine (T3).
AB - In this study the hypothesis that triiodothyronine (T3) and growth hormone (GH)
may have some direct or indirect effect on the regulation of GH-receptor/GH
binding protein (GHR/GHBP) gene transcription was tested. Different
concentrations of T3 (0, 0.5, 2, 10 nmol/l) and GH (0, 10, 150 ng/ml) were added
to human hepatoma (HuH7) cells cultured in serum-free hormonally-defined medium
for 0, 1 and 2 h. Thereafter GHR/GHBP mRNA expression was quantitatively assessed
by using PCR amplification. GH at a concentration of 10 ng/ml resulted in a
significant increase of GHR/GHBP gene expression whereas a supraphysiological
concentration of GH (150 ng/ml) caused a significant decrease of GHR/GHBP mRNA
levels. The simultaneous addition of 0.5 nmol/l T3 to the variable concentrations
of GH did not modify GHR/GHBP mRNA levels whereas the addition of 2 nmol/l up
regulated GHR/GHBP gene expression already after 1 h, an increase which was even
more marked when 10 nmol/l of T3 was added. Interestingly, there was a positive
correlation between the increase of GHR/GHBP mRNA levels and the T3 concentration
used (r: 0.8). In addition, nuclear run-on experiments and GHBP determinations
were performed which confirmed the changes in GHR/GHBP mRNA levels. Cycloheximide
(10 microg/ml) did not alter transcription rate following GH addition but blocked
GHR/GHBP gene transcription in T3 treated cells indicating that up-regulation of
GHR/GHBP gene transcription caused by T3 requires new protein synthesis and is,
therefore, dependent on indirect mechanisms. In conclusion, we present data
showing that T3 on its own has a stimulatory effect on GHR/GHBP gene
transcription which is indirect and additive to the GH-induced changes.
PMID- 10195689
TI - The stimulatory effect of endothelin-1 on frog adrenocortical cells is mediated
through both the phospholipase C and the adenylyl cyclase transduction pathways.
AB - We have previously shown that endothelin-1 (ET-1) stimulates corticosterone and
aldosterone secretion by the frog adrenal gland through activation of ET(A)
receptors. In the present study, we have investigated the transduction pathways
involved in the corticotropic action of ET-1. Exposure of frog adrenal explants
to ET-1 provoked a time- and dose-dependent increase in inositol phosphate
production and a parallel decrease in membrane polyphosphoinositide content.
Incubation of adrenal explants with ET-1 also induced a dose-related increase of
cAMP formation. The selective ET(A) receptor antagonist BQ-485 totally abolished
the stimulatory effects of ET-1 on both inositol phosphate and cAMP production.
In contrast, the selective ET(B) receptor agonist IRL 1620 did not significantly
modify polyphosphoinositide hydrolysis or cAMP formation. Administration of the
phospholipase C inhibitor U-73122 or the protein kinase A inhibitor H-89 to
perifused frog adrenal slices significantly reduced the stimulatory effect of ET
1 on corticosterone and aldosterone secretion. Concomitant administration of the
two inhibitors almost completely suppressed the corticotropic effect of ET-1.
Taken together, these data indicate that, in the frog adrenal gland, the
stimulatory effect of ET-1 on corticosteroid secretion is mediated through
activation of both the phospholipase C and the adenylyl cyclase transduction
pathways.
PMID- 10195690
TI - Conserved amino acids in the ligand-binding and tau(i) domains of the peroxisome
proliferator-activated receptor alpha are necessary for heterodimerization with
RXR.
AB - The peroxisome proliferator-activated receptors (PPARs) are members of the
nuclear hormone receptor superfamily. These ligand-activated transcription
factors are implicated in the regulation of lipid metabolism and adipocyte
differentiation and in the regulation of anti-inflammatory processes. In order to
bind to DNA and activate transcription PPAR requires the formation of
heterodimers with the retinoid X receptor (RXR). We have previously reported that
replacement of a single leucine by an arginine at position 433 of hPPAR alpha
(L433R), located in a highly conserved region of the ninth heptad repeat of a
leucine-zipper-like motif in the ligand binding domain, abolished
heterodimerization of PPAR with RXR and hence its trans-activating capacity. The
aim of our present work was to investigate if other conserved amino acids of the
ligand binding domain are important for heterodimerization of PPAR with RXR. We
found that conserved leucines, L370 and L391, in a leucine-zipper-like motif of
hPPAR alpha, as well as a highly conserved aspartic acid (D304) in the tau(i)
domain are necessary for heterodimerization with RXR. In contrast, mutations of
non-conserved amino acids within the leucine-zipper-like motif do not affect
PPAR:RXR heterodimerization. Surprisingly, we found that some mutants deficient
in heterodimerization with RXR (hPPAR alpha-L370R and -L391R) were still
functional on specific peroxisome proliferator-activator response elements
(PPREs). Both mutants could trans-activate on a PPRE from the P450 cytochrome
promoter CYP4A1, whereas only the hPPAR alpha-L391R mutant could trans-activate
from the acyl-CoA oxidase PPRE (ACOA) and, when stimulated with the peroxisome
proliferator Wy14643, also from the bifunctional enzyme PPRE. We therefore
hypothesize either that: (i) these mutants might be able to heterodimerize with a
protein other than RXR and the affinity for this novel partner may depend on the
nature of the PPRE and to some degree on the choice of the activator, or
alternatively; (ii) that additional nuclear proteins might compensate in vivo for
the decreased binding of RXR to these mutant PPARs observed in vitro.
PMID- 10195691
TI - Acute pretranslational regulation of type III iodothyronine deiodinase by growth
hormone and dexamethasone in chicken embryos.
AB - Both growth hormone (GH) and glucocorticoids are regulators of thyroid hormone
metabolism in vertebrates. Studies on chicken embryos demonstrated that
intravenous (i.v.) injection of chicken GH or glucocorticoids results in
increased plasma 3,3',5-triiodothyronine (T3) concentrations, and this through a
reduction of hepatic type III iodothyronine deiodinase (D3) activity. The recent
cloning of chicken type I iodothyronine deiodinase (D1) and D3 offers the tools
to investigate at what level (pre- or posttranslational) this downregulation of
D3 occurs. Eighteen day old chicken embryos were injected with either 0.9% NaCl
(control), 50 microg dexamethasone (DEX), or 20 microg cGH per animal. Plasma and
tissue samples were taken 5, 10, 30, 60, 120, and 240 min post-injection. Plasma
T3 and thyroxine (T4) were determined as well as in vitro hepatic D1 and D3
activities. Hepatic D1 and D3 mRNA levels were measured by both Northern analysis
and competitive reverse transcription polymerase chain reaction (RT-PCR).
Injection of GH or DEX resulted in a significant increase in plasma T3 when
compared to controls within 30 min post-injection. This increase remained until
the end of the experiment in the DEX-treated group, but not in the GH group. GH
administration had no influence on plasma T4 levels, whereas DEX significantly
reduced plasma T4 from 30 min onwards. Hepatic D1 activity and D1 mRNA levels
showed no changes. Hepatic D3 activity, however, decreased within 10 min after
DEX administration and somewhat slower after GH administration (within 30 min).
Hepatic D3 activity remained low for the remainder of the experiment in the DEX
treated group, whereas D3 activity gradually returned to control levels in the GH
group. This change in hepatic D3 activity was paralleled by the changes in
hepatic D3 mRNA levels (r = 0.88, P = 0.0001) as confirmed by both Northern
analysis and competitive RT-PCR. In conclusion, these results demonstrate that in
embryonic chicken GH and DEX acutely increase plasma T3 levels by decreasing
hepatic D3 activity, a decrease that seems to be regulated predominantly at the
pretranslational level. These results are also an indication for the short half
life (t(1/2)) of the D3 enzyme. The time lag between the effect of GH and DEX on
hepatic D3 mRNA may be due to differences in the mechanism of action between both
hormones, a subject that needs further investigation.
PMID- 10195692
TI - Biosynthesis of secretogranin II in Xenopus intermediate pituitary.
AB - Secretogranin II (SgII) is a sulphated secretory protein found in a broad variety
of neuroendocrine cells. We have raised an antiserum against SgII to monitor its
fate in Xenopus intermediate pituitary. Pulse-chase incubations in combination
with immunoprecipitation analysis showed that SgII was synthesised as an 84-kDa
precursor protein which was processed to fragments of 69, 54, 34, 21 and 15 kDa.
Secretion of these cleavage products was sensitive to the dopamine D2 receptor
agonist apomorphine, and thus occurred via the regulated secretory pathway. When
cells were treated with the fungal metabolite brefeldin A or with the specific
vacuolar H+-ATPase inhibitor bafilomycin A1, the processing of SgII and the
release of its cleavage products were strongly inhibited, indicating that its
processing commenced in the later compartments of the secretory pathway. Pulse
chase and immunoblot analysis showed that the 21-kDa fragment was the major SgII
derived cleavage and release product, and carried secretoneurin, a highly
conserved peptide flanked by potential dibasic processing sites. Hence, SgII is
cleaved to a variety of products that are released via the regulated secretory
pathway, while secretoneurin does not seem to represent a major end-product of
SgII processing in Xenopus intermediate pituitary.
PMID- 10195693
TI - Characterization of the porcine Lhx3/LIM-3/P-Lim LIM homeodomain transcription
factor.
AB - Lhx3/LIM-3/P-Lim is a LIM homeodomain transcription factor which is essential in
mice for the development of anterior and intermediate lobes of the pituitary
gland. We report the cloning and characterization of porcine Lhx3. The porcine
Lhx3 protein exhibits strong similarity to murine Lhx3 within the amino terminal
LIM domains and the homeodomain, however, it is diverged in regions outside these
motifs. Expression vectors for porcine Lhx3 activated murine and porcine alpha
glycoprotein reporter genes in transfection assays, and recombinant porcine Lhx3
protein specifically bound to a target site within the porcine alpha-glycoprotein
gene upstream sequence. In addition, porcine Lhx3 synergistically induced
transcription from prolactin enhancer/promoter reporter genes in cooperation with
the Pit-1 pituitary transcription factor. Porcine Lhx3 protein interacted with
Pit-1 protein in solution and also with the LIM domain-binding protein
NLI/Lbd1/CLIM. Together, these data indicate that many aspects of Lhx3 function
in the mammalian pituitary are conserved and that Lhx3 may be involved in the
activation of trophic hormone genes during early and late stages of pituitary
organogenesis. Divergence in the Lhx3 amino acid sequence between mammalian
species may suggest distinct activities for this protein in some species and may
help identify important functional domains of this key developmental
transcription factor.
PMID- 10195694
TI - Characterization of membrane estrogen binding proteins from rabbit uterus.
AB - Estrogens exert fast non-genomic actions in their target tissues which may
involve the participation of receptors located at the cell membrane. Studies were
performed to identify and characterize membrane-associated 17beta-estradiol
binding proteins in rabbit uterus. Specific and saturable [3H]17beta-estradiol
binding sites of high affinity (Kd = 0.36 nM) were detected in uterine microsomes
at higher concentration than in cytosol (370 +/- 98 vs. 270 +/- 87 fmol/mg
protein, respectively). Various other steroid hormones, the stereoisomer 17alpha
estradiol and the antiestrogen tamoxifen were significantly less effective than
17beta-estradiol to compete with the radioactive ligand for binding to the
membranes. The microsome binding sites were trypsin-sensitive and could be
extracted to a great extent (80-90%) with 0.4/0.6 M KCl. Assays of the marker
enzyme glucose-6-P dehydrogenase excluded membrane contamination with cytosolic
soluble components. Immunoblot analysis of particulate and soluble fractions
using monoclonal antibodies against the transactivation, heat shock protein
recognition, and steroid binding domains of the nuclear estrogen receptor (ER; 67
kDa), revealed lower concentrations of the ER in membranes and the presence of
five additional immunoreactive proteins of 57, 50, 32, 28, and 11 kDa which were
absent in cytosol. Moreover, the antibody against the steroid binding domain was
as effective as an inhibitor for cytosolic and membrane specific radioligand
binding. Extraction of microsomes with the nondenaturing detergent CHAPS allowed
a 2-fold enrichment of ER-like binding proteins as shown by antibody labeling and
[3H]17beta-estradiol binding analysis. The results of this work are consistent
with the existence of novel 17beta-estradiol membrane binding proteins
structurally related to the intracellular ER. Future studies should investigate
whether any of these proteins are involved in the primary events (e.g. receptor
function) mediating nongenomic estrogen effects.
PMID- 10195695
TI - Correlation between expression of peroxisome proliferator-activated receptor beta
and squamous differentiation in epidermal and tracheobronchial epithelial cells.
AB - Previously, several members of the nuclear receptor superfamily have been
implicated in the regulation of epidermal differentiation. In this study, we
analyze the expression of members of the PPAR nuclear receptor subfamily in
relation to the process of squamous differentiation in normal human epidermal
keratinocytes (NHEK), human tracheobronchial epithelial (HBE) cells and the
epidermis in vivo. Our results demonstrate that induction of differentiation in
NHEK by either treatment with the phorbol ester phorbol 12-myristate-13-acetate
(PMA), suspension culture or confluence greatly enhances the expression of
PPARbeta mRNA. Likewise, topical treatment of mouse skin with PMA results in
increased PPARbeta mRNA expression in the epidermis. In addition, the induction
of squamous differentiation in HBE cells was also associated with an upregulation
of PPARbeta mRNA expression. Finally, in situ hybridization analysis localized
PPARbeta mRNA to the suprabasal layers of normal human skin. Our results
demonstrate that the expression of PPARbeta is associated with squamous
differentiation suggesting a regulatory role for this receptor in the control of
specific genes during this differentiation process.
PMID- 10195696
TI - Analysis of proopiomelanocortin gene transcription mechanisms in bronchial tumour
cells.
AB - The ectopic ACTH syndrome results from the transcription of the
proopiomelanocortin (POMC) gene in non pituitary tumors. To determine its
mechanisms, we examined in the human bronchial carcinoma cell line DMS-79
transacting factors binding to the human POMC gene promoter. Three binding sites
were identified in the proximal promoter and proteins were studied by gel-shift
assays. One of them is a binding site for Nur77/Nurr1 proteins in corticotroph
cells but is bound in DMS-79 cells by factor(s) distinct from these proteins. The
remaining two binding sites bound yet unidentified proteins and were both
functionally active in DMS-79 cells. We also showed that DMS-79 cells lacked a
factor required for tissue-restricted POMC gene expression in corticotroph cells.
Altogether, our results indicate that POMC gene expression in DMS-79 cells is
achieved without several of the corticotroph factors and provide a preliminary
characterization of some factors involved in this process. They also reveal that
DMS-79 cells are deficient in proteins involved in the regulation by cAMP and
glucocorticoids.
PMID- 10195698
TI - Characterization of the translated products of the alternatively spliced
luteinizing hormone receptor in the ovine ovary throughout the oestrous cycle.
AB - The luteinizing hormone receptor (LHR) is alternatively spliced. It is not known
if the alternatively spliced mRNAs are translated in vivo, or indeed if they have
any vital role to play. The B splice form has been detected in every species
examined, and it encodes a putative protein with a high affinity LH/CG binding
domain but no trans-membrane or intra-cellular domains. We raised antisera that
recognize the putative protein of the B form, and the closely related G form, and
showed that the B form mRNA is translated in the ovine ovary, but not kidney or
liver. It localized to the luteal cytosolic and microsomal fractions and the
levels declined during regression induced by treatment with prostaglandin
F2alpha. We examined alternative splicing by RNase protection analyses and RT-PCR
analyses of healthy pre-ovulatory follicles, atretic or steroidogenically
inactive follicles, and of newly formed, mid-luteal and regressing corpora lutea.
There was approximately 5-fold more B form mRNA than A form. Thus we have
evidence that the LHR B form is translated in vivo, but no evidence that
alternative splicing of the LHR mRNA is differentially regulated, throughout the
oestrous cycle.
PMID- 10195697
TI - CBP-dependent and independent enhancing activity of steroid receptor coactivator
1 in thyroid hormone receptor-mediated transactivation.
AB - Full-length of steroid receptor coactivator-1 (F-SRC-1) has been shown to
interact with thyroid hormone receptors (TRs) in a ligand-dependent manner and to
stimulate receptor-dependent transcription. To identify functional domains of F
SRC-1, several internal deletion mutants of F-SRC-1 were constructed. Although in
vitro pull down assay with TR showed interaction of all of these mutants with TR,
lack of mid legion (amino acids 398-1172) lost enhancing activity of TR-mediated
transcription in a transient transfection assay. However, F-SRC-1 mutant lacking
CBP-interacting domain still preserved enhancing activity. Surprisingly, F-SRC-1
mutants also increased basal level of viral promoter activity depending upon
their deleted region. Yeast activation function assay revealed that these F-SRC-1
mutants had intrinsic activation function when bound to DNA. Analyses of small
fragments of F-SRC-1 identified three separable activation domains. In vitro
binding assay showed that TBP and TFIIB bound to C-terminal half of F-SRC-1.
These results suggest that F-SRC-1 can function via both CBP-dependent and
independent manners using various sets of activation domains and that direct
interactions between F-SRC-1 and TBP or TFIIB may not be important for CBP
independent transcription.
PMID- 10195699
TI - Prolactin kinase activity in bovine anterior pituitary sub-cellular fractions.
AB - Bovine anterior pituitary cells phosphorylate prolactin (PRL). We describe the
phosphorylation of endogenous and exogenous bPRL in highly enriched subcellular
fractions of bovine anterior pituitary using [gamma-32P]-ATP. 32P-labeling of
endogenous and exogenous bPRL occurred in all subcellular membrane fractions, but
most significantly in the fraction enriched for secretory granules. Zn2+ (0.8
mM), Cu2+ (0.8 mM), and Mn2+ (9.8 mM) increased bPRL phosphorylation by 268, 214,
and 154%, respectively, relative to basal phosphorylation with no added cations.
Neither Mg2+ (10 mM) nor Ca2+ (0.9 mM) increased bPRL phosphorylation above basal
levels. Phosphorylation was dependent on the concentration of Zn2+ with an
apparent Km of 570 microM. bPRL phosphorylation occurred over a wide pH range of
5.9-8.3, with the greatest activity at pH of 6.7 or greater. Phosphorylation of
bPRL was time-dependent. The apparent Kms of the bPRL kinase for exogenous bPRL
and ATP were 15.3 and 267 microM, respectively. bPRL incorporation of 32P was
unaffected by the presence of calcium and calmodulin, cAMP, phosphotidylserine
and diolein, or spermine. From these results we conclude that in vitro
phosphorylation of bPRL occurs under physiological conditions that would be found
in pituitary cells.
PMID- 10195700
TI - Different bioactivities of human thyrotropin receptors with different signal
peptides.
AB - For investigation of the mechanism and pathogenesis of Graves' disease,
availability of a large amount of functional human thyrotropin receptor (TSHR)
capable of recognition by Graves' autoantibodies is essential. Many attempts have
been made to produce the extracellular domain of TSH receptor (TSHRE) in a
baculovirus expression system. However, the receptor is expressed as an insoluble
form and the refolded protein is often not recognized by the autoantibodies. In
this study, we found that the TSHRE expressed with its own signal peptide (VL3
RE) in insect cells is retained inside of the cells and found in both soluble and
insoluble fractions in equal proportion. The signal peptide is not removed. The
receptor in the soluble fraction is not recognized by either TSH or Graves'
autoantibodies. The TSHRE with an insect-specific mellitin signal peptide (Mel
RE) is also retained inside of the cell and found in both the soluble and
insoluble fractions in equal proportion. However, the signal peptide is removed
and the receptor is recognized by the Graves' autoantibodies but not by TSH.
Also, the amount of Mel-RE expressed was 5-10-fold higher than VL3-RE. The two
receptor preparations apparently have the same degree of glycosylation as
evidenced by the same increased mass (approximately 15 kDa) due to glycosylation.
However, the two receptors have different affinity for an anion-exchange resin
and different pI. Deglycosylated receptors have the same pI. This suggests that
the composition of sugars may be different. Taken together, the results suggest
that the two receptors are modified and folded differently by different pathways
due to the presence of different signal peptides. Use of an insect-specific
signal peptide is recommended for expression of TSHR that is recognized by
Graves' autoantibodies in a baculovirus system.
PMID- 10195701
TI - Transcriptional regulation of adrenomedullin in rat vascular smooth muscle cells.
AB - Adrenomedullin (AM), a potent vasorelaxant peptide recently identified in
extracts of pheochromocytoma, is actively secreted from vascular smooth muscle
cells (VSMC). AM production in rat VSMC is potently stimulated by proinflammatory
cytokines including TNF alpha, and glucocorticoids and many vasoactive substances
have also been shown to alter AM synthesis. To study AM promoter function, we
cloned the 5'-flanking region of the rat AM gene, and AM promoter function was
assessed in rat VSMC stably transfected with a construct containing the cloned
fragment. This 1.4 kb AM promoter region includes a number of putative
transcriptional control elements. The promoter activity in VSMC was stimulated by
TNF alpha and dexamethasone, and was suppressed by 8-bromo-cAMP and forskolin.
These data indicate that transcriptional regulation is an important mechanism for
AM production in VSMC.
PMID- 10195702
TI - Growth hormone and the expression of mRNAs for matrix proteins and oncogenes in
bone.
AB - To examine the effects of growth hormone (GH) on the expression of the mRNAs of
bone matrix proteins, three experiments were carried out with 3-month-old female
Sprague-Dawley rats. In the first experiment rats were given a single
subcutaneous injection of recombinant human GH (8 mg rhGH/kg b. wt.), sacrificed
15 min, 1 h, 2 h, 4 h, 8 h, 16 h and 24 h later, and RNA isolated from cancellous
bone from the distal femoral metaphysis. Growth hormone increased the level of
type I collagen mRNA by 187, 417, and 509% over the control level at 15 min, 1 h
and 2 h, respectively; the mRNA levels declined to 119 and 99% at 4 and 8 h,
respectively, and then rose again to 351 and 423% over the control level at 16
and 24 h, respectively. Osteocalcin mRNA transcript increased by 89, 90, 325,
342, 361, and 407% over the control level at 15 min, 1 h, 2 h, 4 h, 8 h and 16 h,
respectively, and fell to 66% at 24 h. The level of IGF-I mRNA increased by 45,
83, 120, 140, and 175% over the control level at 2, 4, 8, 16, and 24 h,
respectively. In the second experiment, following the administration of rhGH (8
mg/kg b. wt.) bone osteocalcin mRNA increased by 127, 177, 361, and 413% over the
control level at 30 min, 1 h, 2 h and 4 h, respectively; IGF-I mRNAs increased by
38, 33, 87, and 437 at 30 min, 1 h, 2 h and 4 h, respectively, but the levels did
not become significant until 2 h; c-fos mRNA increased significantly at 30 min,
and c-jun and c-myc mRNAs did not increase until 4 h. In the third experiment,
animals were given a single injection of rhGH (8 mg/kg b. wt.) and the animals
were bled at timed intervals and acid ethanol-extractable serum IGF-I determined.
Serum IGF-I increased significantly only at 12 h following rhGH administration.
Our data indicate that GH stimulates a rapid increase in the expression of mRNAs
for the bone matrix proteins, type I collagen and osteocalcin, by a mechanism
that appears to be independent of IGF-I, the early response oncogenes or an
increase in osteoblast number.
PMID- 10195703
TI - The lack of gonadotrophin-releasing hormone (GnRH) receptor desensitisation in
alphaT3-1 cells is not due to GnRH receptor reserve or phosphatidylinositol 4,5
bis-phosphate pool size.
AB - The phospholipase C (PLC)-activating gonadotrophin-releasing hormone (GnRH)
receptor is thought not to rapidly desensitise in alphaT3-1 cells. This extremely
unusual characteristic raises the concern that it might be a feature of the cell
type, rather than the receptor per se. Here we have used video imaging to
establish whether the effects of endogenous PLC-activating G-protein coupled
receptors (GPCRs) on Ca2+ ion concentration [Ca2+]i desensitise in these cells.
Oxytocin, endothelin-1, methacholine, and UTP all caused [Ca2+]i increases which
underwent rapid homologous desensitisation in that they were transient and
responses to repeat stimuli were attenuated whereas subsequent responses to GnRH
were not. To test whether receptor reserve obscures functional desensitisation of
GnRH receptors, a photoaffinity antagonist (Pant-1), was used to effect a partial
and irreversible receptor blockade. UV crosslinking in medium with 1000 nM Pant-1
reduced GnRH receptor number to 20 +/- 5% and reduced maximal buserelin
stimulated [3H]IP(X) accumulation to 57 +/- 5%, demonstrating removal of receptor
reserve. In control alphaT3-1 cells the initial rate of GnRH-stimulated [3H]IP(X)
accumulation was maintained for at least 5 min and GnRH caused a sustained
increase in Ins(1,4,5)P3 mass (confirming the resistance of GnRH receptors to
desensitisation) and Pant-1 pre-treatment reduced the magnitude of these
responses without altering their temporal profiles. In alphaT3-1 cells stably
transfected with recombinant human muscarinic receptors (alphaT3-1/M3), responses
to methacholine were characteristic of desensitising GPCRs (transient
Ins(1,4,5)P3 and curvilinear [3H]IP(X) responses) and were unaltered by Pant-1.
To test the relevance of phospholipid pool size, alphaT3-1/M3 cells were pre
treated with GnRH or methacholine in medium with LiCl (to deplete PtdIns(4,5)P2
pools). These pre-treatments reduced subsequent responses to methacholine and
GnRH comparably, indicating access to a shared PtdIns(4,5)P2 pool. Partial
depletion of this pool (GnRH pre-treatment in medium with LiCl) reduced the
magnitude of the [3H]IP(X) and Ins(1,4,5)P3 responses to methacholine and GnRH,
without altering their temporal profiles. Thus the GnRH receptor does not undergo
rapid homologous desensitisation in alphaT3-1 cells in spite of the fact that
they can desensitise other endogenous (and recombinant) PLC-activating GPCRs, and
the lack of desensitisation cannot be attributed to the existence of GnRH
receptor reserve or access to an atypically large or rapidly re-cycled
PtdIns(4,5)P2 pool. This unique functional characteristic (mammalian GnRH
receptors are the only PLC-activating GPCRs known not to rapidly desensitise)
almost certainly therefore reflects the atypical structure of these receptors
(mammalian GnRH receptors are the only PLC-activating GPCRs known to lack C
terminal tails).
PMID- 10195704
TI - White matter injury in the preterm infant: an important determination of abnormal
neurodevelopment outcome.
AB - Periventricular white matter injury, specifically cystic periventricular
leukomalacia (PVL) and ipsilateral hemorrhage into white matter associated with
periventricular-intraventricular hemorrhage (PV-IVH), contribute significantly to
neonatal mortality and long-term neurodevelopmental deficits in the premature
infant. The first lesion PVL occurs in approximately 3-4% of infants of birth
weight (BW) < 1500 grams. It manifests either as a focal or diffuse lesion within
white matter. Although the pathogenesis of PVL is complex and likely
multifactorial, principle contributors include vascular factors which markedly
increase the risk for ischemia during periods of systemic hypotension and the
intrinsic vulnerability of the oligodendrocyte to neurotoxic factors such as free
radicals or cytokines. Clinical associations with PVL include a history of
chorioamnionitis, prolonged rupture of membranes, asphyxia, sepsis, hypocarbia,
etc. The vast majority of infants exhibit long-term neurodevelopmental deficits
that affect motor, cognitive and visual function. The second lesion, the
ipsilateral hemorrhage into white matter lesion associated with PV-IVH, occurs in
approximately 10-15% of infants of BW < 1000 grams. The white matter injury
appears to be a venous infarction with hemorrhage occurring as a secondary
phenomenon. Prevention of this lesion has to include prevention of the associated
PV-IVH. In this regard, the antenatal administration of glucocorticoids has been
associated with a significant reduction in the sonographic incidence of severe
IVH and the associated white matter involvement. The postnatal administration of
indomethacin to high risk infants appears to hold the most promise at the current
time in preventing this lesion. The neurodevelopmental outcome with extensive
white matter injury is universally poor, affecting long-term motor and cognitive
deficits; the long-term outcome is more favorable with lesser involvement. A
clearer understanding of pathogenesis of both conditions is essential so as to
provide targeted preventative strategies.
PMID- 10195705
TI - Chaotic and periodic heart rate dynamics in uncomplicated intrauterine growth
restricted fetuses.
AB - We studied how chaotic and periodic heart rate dynamics differ between normal
fetuses (n = 192) and uncomplicated intrauterine growth restricted fetuses (n =
86), aged 31-42 weeks of gestation. We analyzed each fetal heart rate time series
for 25 min. We quantified the chaotic dynamics of each fetal heart rate time
series by correlation dimension. The periodic dynamics were analyzed by power
spectral analysis. The correlation dimension and, therefore, the complexity, of
the heart rate dynamics of the uncomplicated intrauterine growth restricted
fetuses was significantly lower than that of the normal fetuses, which was marked
at 38-42 weeks of gestation. The low-frequency (0.04-0.15 Hz) component and,
therefore, the periodicity of the low-frequency range was significantly higher
than that of the normal fetuses during all the gestational weeks. These results
mean that, although the intrauterine growth restricted fetuses are not severely
compromised, the overall integrity of their cardiovascular control is impaired,
especially at term; and sympathetic modulation is increased, both of which may
contribute to increased perinatal mortality.
PMID- 10195706
TI - The first-appearance of neutrophils in the human fetal bone marrow cavity.
AB - We sought to define the time of first-appearance of neutrophils within the
developing human bone marrow cavity, and to compare this with the time of
appearance of G-CSF and its receptor (G-CSF-R) at that site. We hypothesized that
the onset of G-CSF production is an initiation signal for neutrophil production
within the marrow cavity, and that therefore G-CSF mRNA and G-CSF protein in the
marrow cavity would immediately precede the first-appearance of neutrophils. To
test this, we determined the time of first-appearance of neutrophils in the
clavicular marrow space using a monoclonal antibody against myeloperoxidase
(MPOAb), and then validated these findings by flow cytometric analyses, for
neutrophil cell-surface markers, of cells flushed from the marrow cavity. After
thus defining the time of first-appearance of neutrophils, specific mRNA
transcripts for G-CSF and G-CSF-R were sought from clavicles of varying
gestational ages, using RT-PCR, and the presence of these proteins in the
clavicles were sought using immunohistochemistry. We observed that; (1) MPO+
cells first appeared in the clavicular marrow cavity between the 10 to 11th weeks
post-conception, (2) Flow cytometric analyses confirmed that these MPO+ marrow
cells included CD11b+, CD15+ neutrophils, (3) Transcripts for G-CSF and G-CSF-R,
and the specific G-CSF and G-CSF-R proteins, were present in the clavicles by 6
weeks post-conception, 4 to 5 weeks before the first-appearance of neutrophils.
Thus, neutrophils first appear in the human clavicular marrow at 10-11 weeks post
conception, and G-CSF and G-CSF-R are present in the developing bone rudiment
preceding the appearance of neutrophils. It is unclear whether neutrophils arise
in the marrow cavity in response to the onset of production of G-CSF or to other
initiation signals.
PMID- 10195707
TI - Anti-insulin antibodies and birth weight in pregnancies complicated by diabetes.
AB - Free insulin cannot cross the placenta but insulin complexed to anti-insulin
antibodies has been demonstrated in cord blood. We studied whether antibody-bound
insulin in diabetic patients can evoke fetal macrosomia independently of maternal
metabolic control. In 457 non insulin-treated controls and 173 insulin-treated
diabetic patients we measured 1187 anti-insulin antibody levels and maternal
blood glucose, maternal fructosamine, cord blood insulin, cord blood C-peptide,
cord blood fructosamine and amniotic fluid insulin. Mean anti-insulin antibody
levels in maternal blood and cord blood were significantly higher in insulin
treated diabetic patients (4.6 and 5.4 U/ml) than in controls (1.8 and 1.7 U/ml)
with maxima of 89.2 in maternal and 120.0 U/ml in cord blood, respectively. In
insulin treated diabetic patients 16.6% (maternal blood) and 22% (cord blood)
anti-insulin antibody levels were above the 97th percentile. There was a high
significant correlation between maternal and cord blood anti-insulin antibodies
(R = 0.987, P = < 0.0001), but no correlation of anti-insulin antibodies with
maternal (glucose, fructosamine) or fetal (insulin, C-peptide, and fructosamine
in cord blood, amniotic fluid insulin) metabolic parameters. While maternal and
fetal metabolic parameters correlated with birth weight neither maternal nor cord
blood anti-insulin antibody levels correlated with birth weight. These findings
do not support the hypothesis that maternal anti-insulin antibodies independently
influence fetal weight.
PMID- 10195708
TI - Maternal and fetal plasma levels of markers of bone metabolism in gestational
diabetic pregnancies.
AB - The aim of this study is to determine whether gestational diabetes has any effect
on maternal and fetal bone metabolism. We collected maternal and umbilical cord
blood samples from 19 women with gestational diabetes and 19 controls at the time
of delivery. The plasma levels of carboxy terminal pro-peptide of type I pro
collagen (PICP) and cross-linked carboxyterminal telopeptide of type I collagen
(ICTP) were used to monitor the rate of bone formation and degradation
respectively. There is a significant correlation between the 1 hour postprandial
blood glucose and the maternal levels of ICTP (r = 0.560, P = 0.004), but there
was no significant difference in maternal or fetal levels of PICP and ICTP
between the study and control groups (P = 0.411 maternal PICP, P = 0.241 maternal
ICTP, P = 0.365 fetal PICP and P = 0.781 fetal ICTP). In the gestational diabetes
group, there was a significant correlation between maternal and fetal ICTP (r =
0.694, P = 0.001), but there was no correlation between maternal and fetal levels
of PICP (r = 0.334, P = 0.175). Although the maternal levels of ICTP is related
to the 1 hour postprandial blood glucose level, gestational diabetes does not
affect the maternal or umbilical cord levels of the serum markers of bone
metabolism.
PMID- 10195709
TI - Postnatal closure of ductus venosus in preterm infants < or = 32 weeks. An
ultrasonographic study.
AB - AIM: To assess ultrasonographically the flow pattern and the time of postnatal
closure of ductus venosus in preterm infants < or = 32 weeks. METHODS: Thirty
three preterm infants < or = 32 weeks were studied within the first 1 to 5 days
of life and followed every second day with ultrasound until no flow was detected
either through the ductus venosus or the ductus arteriosus. RESULTS: The ductus
venosus was closed in only 9% by day 3, in 40% by day 8 and 88% by day 18. All
were closed by day 37. This is significantly later than in healthy term neonates.
Closure of the ductus venosus was not significantly correlated with closure of
ductus arteriosus. CONCLUSION: The ductus venosus shows a delayed closure in
preterm infants, with no significant correlation to the closure of the ductus
arteriosus or the condition of the infant. We speculate that immaturity of the
ductus venosus and possibly increased levels of dilating prostaglandins leads to
a delayed obliteration of the vessel. An open ductus venosus represents a
portocaval shunt and may have metabolical and pharmacological consequences.
PMID- 10195710
TI - The relative accuracy of mercury, Tempa-DOT and FeverScan thermometers.
AB - This project aimed to assess the accuracy of Tempa-DOT and FeverScan for
measuring children's temperatures. Tempa-DOT is a small flat chemical thermometer
with 50 dots that change colour at specific temperatures. FeverScan is a liquid
crystal strip thermometer with temperature sensitive colour bars that change
colour when held against the forehead. Two medical students undertook this study
in a hospital in Zambia. They saw most children presented to the hospital over a
six-week period and on the children's ward. A mercury thermometer was placed in
one axilla, a Tempa-DOT thermometer in the other, and the FeverScan was held on
the child's forehead. Data were obtained from 1090 children with a median age of
two years. The sensitivity of FeverScan to correctly identify febrile children
was 89% and the positive predictive value to detect a fever was 57%. The
sensitivity of Tempa-DOT to correctly identify febrile children was 92% and the
positive predictive value for detecting febrile children was 86%. Tempa-DOT has a
much better predictive value than FeverScan for detecting fever.
PMID- 10195711
TI - Rhythmic changes in the stomach movement of the human fetus with congenital
duodenal obstruction during the third trimester of pregnancy.
AB - In order to reveal whether or not rhythmic changes exist in fetal stomach
movement (FSM), in utero FSM was assessed in three fetuses between 27 and 33
weeks' gestation with congenital duodenal obstruction. A total of four
observations, one each at 27, 29, 31 and 33 weeks' gestation, was obtained. The
longitudinal transection of each fetal stomach was continuously observed for 60
min using real-time ultrasound. The configuration and the area of the stomach
were analyzed for each 15-s epoch. The complexity of the stomach configuration
was quantified and defined as stomach complexity. For each case, the
chronological changes of the stomach complexity were analyzed using the least
median square of regression. The correlation between changes of the stomach
complexity and the area of the stomach was analyzed using the cross-correlation
method. (1) For gestational ages of 27, 29, 31 and 33 weeks, the 240 sequential
measurements of the stomach complexity were significantly stratified into
outlying and non-outlying points. The outlying points were 13.3% (32/240), 30.8%
(74/240), 32.9% (79/240) and 36.3% (87/240) of the total observation points,
respectively. (2) The percentages in which outlying points lasted 3 min (12
points) or more were 0% (0/240), 5.0% (12/240), 28.3% (68/240) and 30.4% (73/240)
of the total observation points, respectively. (3) For each gestational age, no
significant time series correlation was found between the stomach complexity and
the area of the stomach. These findings suggest that: (1) two different
conditions emerge in the FSM, at the latest at 27 weeks' gestation, and begin
manifesting from 29 weeks' gestation onwards. (2) These chronological changes
cluster into 'active' and 'quiet' phases from 31 weeks' gestation onwards. (3)
FSMs are not related to the changes in the stomach area throughout the
observation periods. The underlying mechanism of this rhythmicity may represent
the development of ultradian rhythm of the stomach movement, generated by the
central nervous system.
PMID- 10195712
TI - Newborns spontaneous arm movements are influenced by the environment.
AB - The spontaneous arm movements of 28 healthy full-term newborn infants were
observed for 1 min in four different environmental conditions: each infant was
placed in a vertical position in a bathtub filled with water with the water level
up to her or his neck in a vertical position in water with the water level up to
her or his waist in a supine position out of the water in a vertical position out
of the water. It was hypothesised that these different environmental constraints
would influence the infants spontaneous activity. From video recordings
spontaneous arm movements were categorised according to the classifications of
Hannan (Hannan TE. Young infant's hand and finger expressions: An analysis of
category reliability. In: Field T, Fogel A, editors. Emotion and Early
Interaction. New Jersey: Elbaum 1982;253-265). The statistical analyses showed,
firstly, that the frequency of occurrence of various arm movements is greater out
of the water than in the water. Secondly, for those out of the water the
frequency of occurrence of various arm movements is greater in the vertical
position in comparison to the supine position. Thirdly, the infants showed more
active arm movements (more upward movements) in the vertical position out of the
water in comparison to the two water and supine conditions. These findings lead
to the conclusion that different environmental constraints influenced the
spontaneous arm movements.
PMID- 10195713
TI - A controlled trial of alternative methods of oral feeding in neonates.
AB - BACKGROUND: Some neonatal units are introducing use of cup and traditional
feeding devices for feeding young infants although they have been not been
evaluated objectively. Hence this controlled trial of the use of the bottle, cup
and a traditional feeding device ('paladai') was undertaken in neonates. METHOD:
The study comprised of 100 infants including full-term normal weight infants (n =
66), term growth retarded infants (n = 20), and preterm infants (n = 14). All
three methods were tried on every infant by the same nurse for a particular baby,
so that each infant served as his/her control and in order to avoid the effect of
major influencing factors. Parameters evaluated were the volume ingested,
duration of the feed, degree of spilling and satiety. RESULTS: The infants took
the maximum volume in the least time and kept quiet longest with the paladai. The
findings were particularly significant in the group including all the categories
of infants. Spilling was the highest with the cup, especially with preterm
infants.
PMID- 10195714
TI - Behavioral state affects heart rate response to low-intensity sound in human
fetuses.
AB - The cardiac orienting reflex is elicited by a low-intensity sound, it consists of
a sustained heart rate (HR) deceleration, and it is a specific physiological
correlate of cognitive processing. In this study we examined the relationship
between behavioral state and the cardiac orienting reflex in 75 human fetuses
between 36 and 40 weeks gestation. Each fetus was stimulated with a 30-s speech
sound at an average intensity of 83 dB SPL in quiet sleep (QS) and active sleep
(AS). The fetal cardiac electrical signal was captured transabdominally at a rate
of 1024 Hz and fetal R-waves were extracted using adaptive signal processing.
Fetal behavioral states were assigned based on HR pattern and the presence or
absence of eye and general body movements. We found that a significant HR
deceleration occurred, in both QS and AS, following stimulus onset. However, HR
decelerations occurred more often in QS than AS; and for fetuses exhibiting a HR
deceleration, the magnitude of the deceleration was greater in AS compared to QS.
In addition, in AS female fetuses exhibited a larger, more sustained HR
deceleratory response than male fetuses, but the seconds x gender interaction in
QS was not significant. Based on these results, we concluded that behavioral
state is an important determinant of the HR deceleratory response in human
fetuses.
PMID- 10195715
TI - Predicting infant crying from fetal movement data: an exploratory study.
AB - Using a standardised procedure, 20 women who were 37 weeks pregnant logged fetal
movements for 1 h in the morning and evening for 3 days. Close agreement between
such logs and ultrasound recordings of individual differences in fetal movements
have been documented. After birth, the babies' sleeping, waking, feeding and
crying behaviour were recorded prospectively in validated behaviour diaries at 1,
6 and 12 weeks of age. The fetal movements showed an evening peak, due to a
diurnal variation in strong movements. These strong movements did not predict the
babies' crying. Weak fetal movements provided a reliable index of fetal
differences and predicted the amounts the babies cried at 1, 6 and 12 weeks of
age. The findings suggest that temperament-like dispositions present before
babies are born predict how much they are likely to cry.
PMID- 10195716
TI - Gunshot injuries to the liver: the role of selective nonoperative management.
AB - BACKGROUND: Selective nonoperative management of blunt liver injuries has become
standard practice in most trauma centers. We evaluated the role of selective
nonoperative management of gunshot wounds to the liver. STUDY DESIGN: This was a
retrospective review of gunshot wounds to the liver treated in a level I trauma
center. Patients with peritoneal signs or hemodynamic instability were operated
on without delay. Patients with a soft, nontender abdomen and no signs of heavy
bleeding were selected for nonoperative management. Liver injury was diagnosed by
CT scan. If peritonitis or signs of substantial internal bleeding developed, an
operation was performed; otherwise the patient was discharged within a few days
of admission. Analysis was restricted to the group of patients with isolated
liver injuries. RESULTS: During a 42-month period, 928 patients were admitted
with abdominal gunshot injuries, 152 of whom (16%) had a liver injury. In 52
patients (34% of all liver injuries), the liver was the only injured
intraabdominal organ (4 patients had associated kidney or splenic injuries that
did not require surgical repair). Thirty-six of the patients (69%) with isolated
liver injuries had an emergent operation because of signs of peritonitis or
hemodynamic instability. The remaining 16 patients (31%) were selected for
nonoperative management (3 patients had associated right kidney injury). Five
patients in the observed group required delayed operation because of development
of signs of peritonitis (4 patients) or abdominal compartment syndrome (1
patient). The remaining 11 patients (7% of all liver injuries or 21% of isolated
liver injuries) were managed successfully without operation. One patient with
delayed operation developed multiple complications from abdominal compartment
syndrome, and 1 patient in the nonoperative group had a biloma, which was treated
with percutaneous drainage. CONCLUSIONS: Selected patients with isolated grades I
and II gunshot wounds to the liver can be managed nonoperatively.
PMID- 10195717
TI - Trauma services: a profit center?
AB - BACKGROUND: Previous studies have demonstrated inadequate reimbursement for
severely injured patients with a resultant negative economic impact for the
trauma service and hospital. The purpose of this study was to assess the total
cost of care for all injured patients discharged from the trauma service in
fiscal year 1997, and to determine the proportion of costs for the most severely
injured on total cost. In addition, we assessed the total service costs and the
revenue for treatment of the most severely ill. The final result was the
determination of the profit (loss) margin for the entire service. STUDY DESIGN:
All patients discharged from our Level I Trauma Center in fiscal year 1997 were
included (n = 696). The population was then stratified into 2 subgroups using the
Injury Severity Score (ISS). Patient grouping was facilitated by integration of
the trauma registry with the hospital cost accounting system. The population was
sub-divided into 2 distinct groups. Group A represented all patients with an ISS
>15 (n = 192). Group B contained all patients with an ISS <15 (n = 504). Length
of stay and mortality of each group was recorded. Cost of care was determined by
the hospital cost accounting system TSI (Transition System Incorporated, Boston,
MA), which is designed to generate cost center data on a cost per patient basis.
Total costs were determined for the entire population and Groups A and B. The
proportion of costs consumed by each group was then calculated. Reimbursement was
determined by calculating expected payments for each patient. These calculations
are based on previously agreed upon allowances from each insurer and are
reconciled at the end of each fiscal year to ensure accuracy. RESULTS: The
average length of stay for the population and Groups A and B were 7.5, 9.8, and
6.7 days respectively. Mortality in each group was 9.7%, 19.3%, and 6%. Over 92%
of the population sustained blunt mechanism injury and only 8% were penetrating.
When controlled for length of stay, the profit margin for Group A is $1,242/day
and for Group B is $519/day. Comparison of mean cost/patient between Group A and
Group B was $35,727 versus $17,623, respectively. CONCLUSION: Trauma centers can
be profitable. Group A is responsible for 44% of the total service cost while
accounting for only 28% of the discharges. Moreover, this group is responsible
for 57% of the profit, and yields the greatest return. The ability to care for
the sickest patients, while enormously costly, is essential to the economic
viability of the trauma center and its future growth.
PMID- 10195718
TI - Pain after primary inguinal herniorrhaphy: influence of surgical technique.
AB - BACKGROUND: Pain is an important problem after ambulatory hernia repair. To
assess the influence of the surgical technique on postoperative pain, two
separate randomized, patient-blinded, controlled trials were performed in men
with an indirect inguinal hernia. STUDY DESIGN: In study A, 48 patients with an
internal inguinal ring smaller than 1.5 cm were randomly allocated to either
simple extirpation of the hernial sac or extirpation plus annulorrhaphy. In study
B, 84 patients with an internal inguinal ring wider than 1.5 cm were randomly
allocated to extirpation plus annulorrhaphy or extirpation plus Lichtenstein mesh
repair (modified). All operations were performed under unmonitored local
anesthesia with standardized perioperative analgesia using methadone and
tenoxicam. Pain was scored daily for the first postoperative week and after 4
weeks on a four-point verbal-rank scale (no, light, moderate, or severe pain)
during rest, while coughing, and during mobilization (rising to the sitting
position). Use of supplementary analgesics (paracetamol) was recorded. Cumulative
daily pain scores for the first postoperative week and the number of patients who
used supplementary analgesics were the main outcome measures. RESULTS: There were
no significant differences in cumulative pain scores or use of supplementary
analgesics between the treatment groups in either study. Cumulative pain scores
were significantly higher during coughing and mobilization than during rest in
both studies. CONCLUSIONS: Choice of surgical technique for open repair of a
primary indirect inguinal hernia has no influence on postoperative pain.
PMID- 10195719
TI - Laparoscopic ultrasonography versus operative cholangiography during laparoscopic
cholecystectomy: review of the literature and a comparison with open
intraoperative ultrasonography.
AB - BACKGROUND: Laparoscopic ultrasonography (LUS) has been used increasingly over
the last several years as a new imaging modality. To define the role of LUS
during laparoscopic cholecystectomy, we evaluated LUS by prospectively comparing
it with operative cholangiography (OC), by reviewing the literature on LUS, and
by retrospectively comparing it with intraoperative ultrasonography performed
during open cholecystectomy. STUDY DESIGN: LUS and OC were compared prospectively
in 100 consecutive patients during laparoscopic cholecystectomy. The success rate
of examination, the time required, the accuracy in diagnosing bile duct calculi,
and the delineation of biliary anatomy were evaluated. RESULTS: The success rate
of examination was 95% for LUS and 92% for OC. The main reason for unsatisfactory
LUS was incomplete visualization of the distal common bile duct. The time
required was 8.2 minutes for LUS and 15.9 minutes for OC (p<0.0001). Nine
patients had bile duct calculi. LUS had one false-negative result and OC had two
false-positives and one false-negative. The accuracies of LUS and OC were
comparable except for a slightly better positive predictive value of LUS (100%
versus 77.8%; p>0.1). In a literature review, 12 recent prospective studies
comparing LUS and OC and three studies on open intraoperative ultrasonography
were reviewed. Twelve studies of LUS with a total of 2,059 patients demonstrated
results similar to the present study. The success rate was 88% to 100% for both
tests. The time for LUS was approximately 7 minutes, about half of the time
needed for OC. Overall, LUS was associated with fewer false-positive results than
OC; the positive predictive value and specificity of LUS were better, while the
sensitivity and negative predictive value of LUS and OC were comparable. OC
detected ductal variations or anomalies more distinctly than LUS. Compared with
open intraoperative ultrasonography, LUS had a slightly lower success rate and
required a slightly longer time because it was technically more demanding, but
the two procedures had a similar accuracy for diagnosing bile duct calculi.
CONCLUSIONS: Because of their different advantages and disadvantages, LUS and OC
can be used in a complementary manner. There is a learning curve for LUS because
of its technical difficulty. Once learned, however, LUS can be used as the
primary screening procedure for bile duct calculi because of its safety, speed,
and cost-effectiveness. OC can be used selectively, particularly when ductal
anatomic variations or anomalies or bile duct injuries are suspected.
PMID- 10195720
TI - Comparison of costs between laparoscopic and open Nissen fundoplication: a
prospective randomized study with a 3-month followup.
AB - BACKGROUND: Laparoscopic antireflux surgery has replaced conventional operation
despite the fact that currently no randomized trials have been published
regarding its cost effectiveness. The objective of the present study was to
compare costs and some short-term outcomes of laparoscopic and open Nissen
fundoplication. STUDY DESIGN: Forty-two patients with documented gastroesophageal
reflux disease were randomized between October 1995 and October 1996 to either
laparoscopic (LNF) or open (ONF) Nissen fundoplication. Some short-term outcomes,
Gastrointestinal Quality of Life Index (GIQLI) hospital costs, and costs to
society were assessed. Followup was 3 months. RESULTS: Medians of operation times
in the LNF and ONF groups were 98 min and 74 min, respectively. Hospital stay was
2.5 days shorter after laparoscopic operation (LNF 3 days versus ONF 5.5 days).
Both operations were equally safe and effective, but the LNF group experienced
significantly less pain and fatigue during the first 3 postoperative weeks.
Improvement in the GIQLI and overall patient satisfaction were comparable between
the methods. Convalescence was faster in the LNF group: return to normal life
being 14 versus 31 days and return to work being 21 versus 44 days in the LNF and
ONF groups, respectively. Hospital costs were similar, $2,981 and $3,140 in the
LNF and ONF groups, respectively, but total costs were lower ($7,506 versus
$13,118) in the LNF group as a result of an earlier return to work. CONCLUSIONS:
LNF is superior in cost effectiveness, assuming that the longterm results between
the methods are comparable.
PMID- 10195721
TI - Sentinel lymph node biopsy in breast cancer: unfiltered radioisotope is superior
to filtered.
AB - BACKGROUND: The combination of gamma-probe radiolocalization and blue-dye mapping
of sentinel lymph nodes (SLNs) has been advocated as the most accurate method for
staging the clinically negative axilla in breast cancer patients, but the
technical aspects of these procedures are not fully characterized in the
literature. In this study, we compared the success of SLN localization in 134
consecutive breast cancer patients using blue dye plus two different preparations
of radiocolloid. STUDY DESIGN: A retrospective analysis of a prospectively
maintained data base was performed to assess SLN localization in two cohorts of
patients. Unfiltered technetium-99m (Tc-99m) sulfur colloid (in 77 patients;
group I) was compared with filtered Tc-99m sulfur colloid (in 57 patients; group
II). All patients had a peritumoral injection of blue dye and isotope, followed
immediately by lymphoscintigraphy to confirm radioactivity at the injection site
and to image the SLN. Statistical analysis was performed using the Pearson chi
square test. RESULTS: Unfiltered Tc-99m sulfur colloid was superior to the
filtered radiocolloid in localizing the SLN (88% versus 73%; p = 0.03). SLN
imaging by lymphoscintigraphy was also more successful in the unfiltered group.
Using the combination of blue dye and radiolocalization, SLNs were identified in
94% of patients. CONCLUSIONS: For optimal localization of the SLN in breast
cancer patients, surgeons should use the combined technique of blue-dye mapping
and gamma-probe localization using unfiltered Tc-99m sulfur colloid.
PMID- 10195722
TI - Heterogeneous gland size in sporadic multiple gland parathyroid hyperplasia.
AB - BACKGROUND: The success rate for bilateral exploration in patients with primary
hyperparathyroidism approaches 95%. Multiglandular parathyroid hyperplasia
accounts for approximately 10% to 30% of primary hyperparathyroidism. The
incidence of recurrent or persistent hyperparathyroidism is highest in familial
forms of the disease, in which multiglandular disease is more common; this may be
due to asymmetric enlargement of parathyroid glands. Because of improvements in
tumor-imaging capability, some surgeons are now advocating unilateral exploration
for primary hyperparathyroidism, but there is limited experience concerning how
often these imaging methods fail. STUDY DESIGN: The outcomes of 7 patients who
had sporadic primary hyperparathyroidism with multigland hyperplasia were
reviewed. We gathered demographic data and laboratory values and reviewed
radiologic tests, surgical findings, pathologic findings, and postoperative
followup. RESULTS: All patients underwent preoperative localization with
ultrasonography and technetium/sestamibi scans. The sensitivity of these two
tests for the dominantly enlarged gland was 100% for both, but dropped to 0% and
5%, respectively, for all other enlarged glands. The sensitivity of CT and MRI
for the dominant tumor was 67% (2 of 3) and 50% (1 of 2), respectively. Six of 7
patients underwent subtotal (3(1/2) gland) parathyroidectomy. The mean volume of
all glands was 1.51+/-5.89 cm3 compared with a mean of 5.66+/-11.4 cm3 for all
dominant glands and 0.123+/-0.1 cm3 for all nondominant hyperplastic glands.
There was a large amount of variability between the volumes of dominant and other
glands as demonstrated by large SDs from the mean. CONCLUSIONS: There is a marked
heterogeneity in gland size in patients with sporadic multigland hyperplasia,
which is similar to that found in multiple endocrine neoplasia type I. This
heterogeneity may result in failure to recognize multigland disease if a
unilateral neck exploration is performed. Intraoperative parathyroid hormone
assay may prove to be an important adjunct in this population of patients who
have unsuspected multigland disease.
PMID- 10195723
TI - Intussusception in adults: institutional review.
AB - BACKGROUND: Intestinal intussusception in the adult is a rare entity that differs
greatly in etiology from its pediatric counterpart. Controversy remains regarding
the optimal management of this problem in the adult patient. The purpose of this
study was to determine the cause(s) of intussusception and to determine the role
of intestinal reduction in the management of intussusception in adults. STUDY
DESIGN: A retrospective review performed at The Mount Sinai Medical Center
identified 27 patients, 16 years and older, with a diagnosis of intestinal
intussusception. Data related to presentation, diagnosis, treatment, and
pathology were analyzed. RESULTS: There were 13 males and 14 females. The median
age of the group was 52 years with a range of 16 to 90 years. Abdominal pain was
the most common presenting complaint. A preoperative diagnosis was suspected in
11 of 27 patients (40%). There were 22 small bowel lesions and 5 colonic lesions.
A pathologic cause was identified in 85% of patients with 8 of 22 (36%) small
bowel and 4 of 5 (80%) of large bowel lesions being malignant. All small bowel
cancers represented metastatic disease and all large bowel malignancies were
primary adenocarcinomas. The median age of patients with malignant disease was 60
years; it was 44 years for those with benign disease. Operative treatment
consisted of resection alone in 58% of patients and resection after reduction in
42%. Three patients were treated nonoperatively. CONCLUSIONS: Our data support a
selective approach to the operative treatment of intussusception in adults.
Colonic lesions should not be reduced before resection because they most likely
represent a primary adenocarcinoma. Small bowel intussusception should be reduced
only in patients in whom a benign diagnosis has been made preoperatively or in
patients in whom resection may result in short gut syndrome.
PMID- 10195724
TI - Budd-Chiari syndrome caused by Behcet's disease: treatment by side-to-side
portacaval shunt.
AB - BACKGROUND: Behcet's disease is a chronic multisystem vasculitis of unknown
etiology that involves skin, mucous membranes, eyes, blood vessels, joints,
central nervous system, digestive system, and occasionally other organs. Budd
Chiari syndrome from occlusion of the major hepatic veins is a rare and serious
complication of Behcet's disease. Although the mortality rate of Behcet's disease
is only 3% to 4%, development of Budd-Chiari syndrome in patients with Behcet's
disease has been associated with a mortality rate of 61%. This report presents
the largest reported experience of Behcet's disease-related Budd-Chiari syndrome
confined to the hepatic veins, and results of treatment by side-to-side
portacaval shunt (SSPCS). These results are compared with those we have obtained
in Budd-Chiari syndrome confined to the hepatic veins without Behcet's disease,
and with results of treatment of Budd-Chiari syndrome in Behcet's disease
reported in the literature. STUDY DESIGN: SSPCS was performed in 5 patients with
Behcet's disease who had developed acute Budd-Chiari syndrome, and 27 patients
with Budd-Chiari syndrome from other causes. In all patients, Budd-Chiari
syndrome was confined to the hepatic veins without involvement of the inferior
vena cava (IVC). Patients were studied prospectively and were followed up at
regular intervals for from 1.5 to 26 years (mean 10.6 years, 81% more than 5
years). Followup was 100%. Patients were mainly young adults; mean age was 24.6
years in the patients with Behcet's disease and 30.0 years in those without
Behcet's disease. All patients had massive ascites, abdominal pain,
hepatosplenomegaly, and abnormal liver function. Diagnosis was based on
angiographic demonstration of occlusion of the major hepatic veins, and liver
biopsy findings of intense hepatic congestion and necrosis. SSPCS was performed
within 4 months of the onset of Budd-Chiari syndrome in all but 3 patients. Every
year or two in followup, patients underwent liver biopsy and evaluation of SSPCS
by Doppler duplex ultrasonography and angiography with pressure measurements.
Outcomes criteria included mortality rate, SSPCS patency, maintenance of portal
decompression, liver function, presence of ascites, presence of portal-systemic
encephalopathy (PSE), need for diuretics, quality of life, and return to work.
Our results were compared with those reported in the literature in 42 patients
who had Budd-Chiari syndrome with Behcet's disease. RESULTS: SSPCS permanently
reduced the mean portal vein-IVC pressure gradient (mm saline) from 205 to 7 in
the 5 patients with Behcet's disease, and from 250 to 4 in the 27 without
Behcet's disease. There was only one operative death, a patient without Behcet's
disease. One patient with Behcet's disease died 2 years postoperatively from
diffuse vasculitis, a complication of Behcet's disease, and the other 4 (80%)
remain alive. All 26 operative survivors in the group without Behcet's disease
(96%) are alive. Only one patient developed occlusion of the SSPCS, a man without
Behcet's disease, and he required liver transplantation as a result of hepatic
decompensation, PSE, and recurrent ascites. All other patients with or without
Behcet's disease remained free of ascites, required no diuretics, were free of
PSE, and had reversal of hepatic dysfunction. Serial liver biopsies showed normal
architecture in 60% of patients with Behcet's disease and 46% of those without
Behcet's disease. Return to fulltime work or housekeeping occurred in 80% of
patients with Behcet's disease and 96% without Behcet's disease. Comparison of
outcomes of our patients with 42 cases of Behcet's disease with Budd-Chiari
syndrome reported in the literature, 79% of whom were treated medically, showed
striking differences with an overall mortality rate of 61% in generally shortterm
followup. (ABSTRACT TRUNCATED)
PMID- 10195725
TI - Fungal infection in acute necrotizing pancreatitis.
AB - BACKGROUND: Anecdotal reports suggest that patients with fungal infection of
necrotizing pancreatitis (NP) have worse outcomes than those with bacterial
infection. Our aim was to compare the clinical course and outcomes of patients
with NP infected with fungal versus nonfungal organisms. STUDY DESIGN:
Prospectively collected data on 57 patients with infected NP (1983-1995) were
reviewed. RESULTS: Seven patients (12%) developed fungal infection, and 50 (88%)
developed bacterial infection. Groups had similar mean ages (60 versus 63 years)
and APACHE-II scores on admission (9 each). The cause of NP was ERCP-induced in 3
of 7 with fungal infection versus 3 of 50 with bacterial infection. Patients with
fungal infection had been treated with a mean of 4 different antibiotics for a
mean of 23 days, and 4 of 7 (57%) required mechanical ventilation preoperatively.
In addition, postoperative ICU stays were longer (20 versus 10 days), as were
total hospital stays (59 versus 41 days). Mortality was higher with fungal
infection; 3 of 7 patients (43%) died versus 10 of 50 patients (20%).
CONCLUSIONS: Although NP presents with similar initial severity, patients with
fungal infection of NP tend to have a more complicated course and worse outcomes
compared with those with bacterial infection. Low-dose antifungal prophylaxis
should be added to early management of NP.
PMID- 10195726
TI - Diagnostic and prognostic values of CA 19-9 and CEA in periampullary cancers.
AB - BACKGROUND: The roles of carcinoembryonic antigen (CEA) and carbohydrate antigen
19-9 (CA 19-9) in periampullary cancers have not been clearly established.
Diagnostic and prognostic values of these two tumor markers were clarified in
this study. STUDY DESIGN: Preoperative serum levels of CEA and CA 19-9, and
clinicopathologic features were retrospectively reviewed in 143 surgical patients
with periampullary cancer from 1989 to 1997. RESULTS: There were 86 resectable
and 57 unresectable periampullary cancers. CA 19-9 demonstrated significantly
higher sensitivity in detecting these cancers than CEA. The cancer with
unresectable lesion, total bilirubin >7.3 mg/dL, or tumor size >2 cm tended to
associate with higher CA 19-9 level. CEA level was significantly higher in the
tumor >2 cm, not in the tumor < or =2 cm. CA 19-9 was a significant prognostic
factor in both resectable and unresectable periampullary cancers, but CEA was
significant only in the resectable group. Multivariate analysis revealed that
independent prognostic factors included CA 19-9, resectability, primary tumor,
and stage, and CA 19-9 was the most important one. CONCLUSION: CA 19-9 provided
more important diagnostic and prognostic values than CEA in periampullary cancers
and was the most important independent prognostic factor for periampullary
cancers. This study recommends serum CA 19-9 as an adjunct in detecting
periampullary cancers, in evaluating resectability, and in predicting prognosis.
PMID- 10195727
TI - Positive peritoneal cytology predicts unresectability of pancreatic
adenocarcinoma.
AB - BACKGROUND: Peritoneal cytology is clinically useful in gastric and gynecologic
malignancies. Its role in pancreatic adenocarcinoma remains less well defined.
Controversy exists as to the relationship between percutaneous fine needle
aspiration (FNA) of the pancreas and shedding of malignant cells with the
peritoneum. The aim of this study was to determine whether positive peritoneal
cytology (PPC) predicts unresectability of pancreatic adenocarcinoma and impacts
on overall survival. In addition, the study aimed to determine whether antecedent
FNA increases the incidence of PPC. STUDY DESIGN: Between January 1993 and June
1996, 228 patients with radiographically resectable pancreatic adenocarcinoma
underwent laparoscopic staging. Specimens were taken from right and left upper
quadrants at the beginning of laparoscopy. Various prognostic factors were
analyzed. RESULTS: PPC was identified in 34 patients (15%). Of patients that had
an antecedent FNA, 20% had PPC, and 13% of those without an antecedent FNA had
PPC (p = 0.22). The majority of patients with PPC had stage IV disease (26 of 34
[76%]) and only 8 (24%) had no evidence of metastases. Overall survival was
significantly higher in patients with negative peritoneal cytology (NPC) compared
with PPC (p<0.0006). PPC had a positive predictive value of 94.1%, specificity of
98.1%, and a sensitivity of 25.6% for determining unresectability of pancreatic
adenocarcinoma. PPC was not an independent prognostic variable for survival on
multivariate analysis. CONCLUSIONS: PPC is associated with advanced disease and
is highly specific in predicting unresectability of pancreatic adenocarcinoma,
resulting in decreased survival. Antecedent FNA is not associated with an
increased the incidence of PPC, nor does it significantly impact on overall
survival.
PMID- 10195728
TI - When is nonoperative management of a gunshot wound to the liver appropriate?
PMID- 10195729
TI - Incisional hernia: the problem and the cure.
PMID- 10195730
TI - Healing of the cervical esophagogastrostomy.
PMID- 10195731
TI - Titanium miniplates for the surgical correction of pectus excavatum.
PMID- 10195732
TI - Central integrative role of oestrogen in modulating the communication between the
placenta and fetus that results in primate fecal-placental development.
AB - This review summarizes the experimental evidence supporting the concept that
oestrogen has a central integrative role in modulating the communication that
occurs between the placenta and the fetus which results in primate fetal
placental development. Thus oestrogen, acting within placental trophoblasts,
regulates the functional differentiation of syncytiotrophoblasts, manifested as
an upregulation of key components of the progesterone biosynthetic pathway and
the 11beta-hydroxysteroid dehydrogenase (11beta-HSD)-1 and -2 enzymes controlling
cortisol-cortisone interconversion. The increase in 11beta-HSD expression results
in the switch in the qualitative and quantitative patterns of transplacental
corticosteroid metabolism that induces maturation of the primate fetal
hypothalamic pituitary adrenocortical axis. The studies outlined in this review,
therefore, provide new insight into the role that oestrogen plays during the
course of primate pregnancy and demonstrate that an oestrogen-dependent
signalling system exists in utero that coordinates the placental and fetal
dialogue critical to development of the placenta and endocrine systems underlying
neonatal self-sufficiency.
PMID- 10195733
TI - Flexner's Na+ clearances and the histological structure and age of the placenta
in various species.
AB - 1939 and the early 1940s saw the publication of a remarkable series of papers on
placental transfer. For the first time, a group of investigators made a
quantitative and systematic study of the transfer of a simple, presumably inert
physiological solute, the sodium ion, in a number of different species at various
gestational ages. The driving force behind these studies was Louis Barkhouse
Flexner.
PMID- 10195734
TI - Electrogenic sodium transport mediated by an amiloride-sensitive conductance in a
porcine trophectoderm cell line.
AB - This study examined the electrical properties and Na+ transport function of a
porcine trophectoderm cell line, TE1, which forms a polarized epithelium in
culture. Specifically, the capacity of TE1 cells to generate a transepithelial
potential difference, and to modify selectively the Na+, K+ and Cl- ionic
composition of medium in the apical and basolateral compartments, was examined
over a 48-h period using monolayers cultured on permeable tissue culture
supports. TE1-cell monolayers formed 'tight epithelia' in that significant
transepithelial electrical resistances (RT; median value 5.30 k(ohms)/cm2, range
2.26-9.18 k(ohms)/cm2, n = 72), and electrical potential differences (VT; maximum
mean value at 24 h, 42.9 mV, SEM 7.14; n = 6) were generated. It is concluded
that: (1) the VT was generated by the amiloride-sensitive, Na+ absorptive
function; (2) K+ transport across the monolayers was related to the electrogenic
Na+ transport function; and (3) the three ions traverse the epithelium by active
transport or co-transport, rather than simple diffusion. These data substantiate
the proposed role for porcine trophectoderm of generating electrical and chemical
potentials in vivo, and for regulating the environment of the blastocoel cavity
in the pre-implantation porcine embryo.
PMID- 10195736
TI - Uptake of L-triiodothyronine sulphate by human choriocarcinoma cell line, JAr.
AB - This study investigated uptake of triiodothyronine sulphate (T3S) and
interactions between uptake of T3S and triiodothyronine (T3) using the human
choriocarcinoma cell line (JAr) as a model of placental transport. Cells were
incubated at 37 degrees C with 30 pM 125I-T3 for 2 min with unlabelled T3 (0-30
microM) or T3S (0-1 mM). Addition of an excess unlabelled T3 (30 microM) or T3S
(1 mM) reduced the initial rate of 125I-T3 uptake by 69.3+/-3.6 per cent
(P<0.0001) and 52.9+/-7.8 per cent (P<0.0001), respectively. The calculated
Michaelis constant (Km) for T3 uptake was 0.378+/-0.133 microM (n = 3) with a
corresponding maximum velocity (Vmax) of 15.4+/-6.9 pmol/min/mg protein. Uptake
of 125I-T3 was inhibited in a dose-dependent way by the addition of unlabelled
T3S (0-1 mM). The calculated inhibition constant (Ki) for the inhibition of 125I
T3 uptake by T3S was 121.8+/-35.2 microM (n = 6). Saturable uptake of 125I-T3S by
JAr cells was negligible. The T3S preparation incubated with the cells contained
about 0.1 per cent T3, sufficient to explain the apparent inhibition of 125I-T3
uptake by unlabelled T3S. These results suggest that, in contrast to T3 uptake in
these cells, JAr cells do not have a saturable uptake mechanism for T3S, and that
T3S does not interact with the T3 transporter in these cells.
PMID- 10195735
TI - Gestational development of water and non-electrolyte permeability of human
syncytiotrophoblast plasma membranes.
AB - In order to establish a gestational profile for placental transcellular
permeabilities to water, urea and mannitol, syncytiotrophoblast microvillous
(MVM) and basal membrane (BM) vesicles were isolated from human placentae
obtained from 16 weeks of gestation to term. Using stop-flow/light-scattering
techniques the rate of change in vesicle volume in response to an osmotic
challenge was measured and osmotic water permeabilities (Pf) and solute
permeabilities (Ps) calculated. Membrane fluidity was assessed by steady-state
DPH anisotropy. Permeability of MVM to water and solutes increased by 20-30 per
cent in mid-pregnancy and declined again after the 36th week of gestation. In BM,
this pattern was apparent only for water permeability; solute permeabilities were
not significantly altered. MVM cholesterol content was approx two-fold higher and
membrane fluidity lower compared to BM. Cholesterol content in BM, but not in
MVM, increased during the late third trimester. Membrane fluidity did not change
consistently during gestational development. We conclude that syncytiotrophoblast
plasma membranes exhibit small but significant changes in passive permeability to
water and non-electrolytes from 16 weeks of gestation to term. It is suggested
that an increased water permeability of the syncytiotrophoblast plasma membranes
might contribute substantially to the gestational increase in water exchange
across the human placenta observed in vivo.
PMID- 10195737
TI - Transport of sugars across human placental membranes measured by light
scattering.
AB - The goal of this research was to investigate movement of sugars across placental
plasma membranes. Changes in vesicle volume produced by solute uptake were
measured by light scattering. Analysis, performed by fitting of the light
scattering data to exponentials, revealed that for certain sugars such as
glucose, a rapid component and a second, slower transport process were present.
Measurements in the presence of the glucose transport inhibitor phloretin,
comparison with the transport of mannitol and analysis of the concentration
dependence of the two transport components were used to demonstrate that these
two processes are consistent with protein-mediated and lipid-diffusional
transport of glucose. Calculation of glucose flux rates using the time constants
which define these processes provided values similar to those determined by
radioisotopic methods. Glucose, 2-deoxyglucose and galactose were transported
both by carrier-mediated and diffusional processes, while mannitol, fructose,
ribose and 2-deoxyribose were transported solely by the latter process and not by
a protein carrier. The rate of glucose transport across the syncytiotrophoblast
basal membrane was slightly greater than that across the microvillous membrane,
in contrast to that predicted previously by immunoblotting. In addition,
measurements of hexose transmembrane diffusion showed that microvillous and basal
transport rates were similar and lower than previously determined. We conclude
that this new technique represents a simple and rapid method for investigating
sugar transport across placental membranes.
PMID- 10195738
TI - Amniotic fluid lactoferrin in intrauterine infection.
AB - Lactoferrin (LF) has been found in most biological fluids including amniotic
fluid and cervical mucus in pregnant women and is released from neutrophils in
response to inflammation. It is an important component of the host defence
against microbial infections due to its antimicrobial properties. Premature
labour is caused by amniotic infection and high concentrations of inflammatory
cytokines in amniotic fluid with infection are well established. In the present
study, LF levels of intrauterine infection in amniotic fluid were measured and
the biological significance of LF was investigated. The effects of LF on IL-6
production in cultured amnion cells were also investigated. The concentrations of
LF and IL-6 in amniotic fluid with chorioamnionitis (CAM) were 8.76+/-0.65
microg/ml and 6.92+/-4.88 ng/ml (n = 28), respectively, and both were
significantly higher (P<0.01) than those without CAM (0.86+/-0.81 microg/ml and
0.34+/-0.25 ng/ml; n = 31). LF and IL-6 levels were significantly higher (P<0.01)
with CAM. A significant positive correlation between LF and IL-6 levels in
amniotic fluid was found (r = 0.91, P<0.01). To our knowledge, this was the first
study of its kind, which shows that IL-6 production induced by lipopolysaccharide
in cultured cells was significantly inhibited below physiological concentration
of LF in the amnion. In addition, the immunohistochemical localization of LF in
fetal membranes was investigated. In the fetal membranes with CAM, strong
positive staining was observed in amniotic and chorionic membranes, with
leucocyte migration, while weak staining was observed in membranes without CAM.
These results show conclusively that LF suppresses amniotic IL-6 production under
the conditions of intrauterine infection.
PMID- 10195739
TI - Region and labour-dependent synthesis of prostaglandin E2 by human fetal
membranes.
AB - To examine the effect of region and labour upon prostaglandin synthesis in human
fetal membranes, intact membranes from three regions, the cervical region, the
periplacental region and a region midway between the two, were collected
following spontaneous labour and delivery or at elective caesarean section prior
to labour. Discs of 2-cm diameter were cut from each of three regions and
incubated for 1, 2, 4, 6, 12 or 24 h after which prostaglandin E2 concentration
in the supernatant was measured. We found that there was an overall decrease in
prostaglandin synthesis in tissues collected after labour, but that this effect
could be reversed if exogenous arachidonic acid substrate was supplied. We found
no differences in prostaglandin synthesis between tissues collected from each of
the three regions. We conclude that prostaglandin synthesis from the fetal
membranes during labour leads to depletion of arachidonic acid substrate and that
regional changes in prostaglandin dehydrogenase activity do not appear to have a
significant effect upon overall prostaglandin synthesis.
PMID- 10195740
TI - Polymorphonuclear leukocytes in the fetal membranes are activated in patients
with preterm delivery: ultrastructural and enzyme-histochemical evidence.
AB - The purpose of this study was to examine evidence for the presence of activated
leukocytes in the fetal membranes from patients with preterm delivery.
Polymorphonuclear leukocytes in fetal membranes from seven patients with preterm
delivery (26-32 weeks of gestation) were analysed using transmission electron
microscopy and ultrastructural enzyme-histochemistry for peroxidase and alkaline
phosphatase. A large number of leukocytes accumulated in the fetal membranes from
preterm deliveries. Phagosome, phagocytosis of cell debris, attachment of primary
granules to the phagosomal membrane and cell surface projections were observed in
fetal membrane leukocytes from preterm delivery but not in peripheral blood
leukocytes. Peroxidase and alkaline phosphatase activity was demonstrated on the
plasma membrane of the phagosomes. Morphological and enzyme-histochemical
observation indicated that polymorphonuclear leukocytes in the fetal membrane in
patients with preterm delivery were stimulated or activated. Such activated
leukocytes may play a role in the pathophysiology or pathogenesis of preterm
delivery.
PMID- 10195741
TI - Biological activities of a human amniotic membrane interferon.
AB - In order to characterize further the human amniotic membrane interferon (IFN-AM),
an interferon antigenically unrelated to human IFN-alpha, -beta, and -gamma or
TNF, we analysed its biological activities. Here, we present direct evidence of
its ability to affect cell growth and to induce the IFN-stimulated genes (ISGs) 6
16 and 2'-5' oligoadenylate synthetase (OAS), in addition to its crossed anti
viral activity. The cellular growth arrest effect of IFN-AM was dose-dependent
and paralleled that of IFN-beta. IFN-AM was also able to inhibit thymidine
incorporation into DNA, similar to IFN-beta. The mRNA induction of 6-16 gene with
IFN-AM treatment reached its highest level at 500 IU/ml and remained constant up
to 2000 IU/ml. Conversely, 2'-5' OAS mRNA induction was dose-dependent, with the
maximum level detected at 2000 IU/ml of IFN-AM treatment. The time course of mRNA
accumulation by ISGs with IFN-AM (500 IU/ml) stimulation was also investigated.
Gene induction reached a maximum at 16 h after IFN treatment for 2'-5' OAS and at
48 h for the 6-16 gene. IFN-AM and human IFN-alpha induced similar levels of the
OAS enzyme. IFN-AM also showed small but significant activity in bovine cells. In
conclusion, the amniotic membrane IFN here studied showed both anti-cellular
activity and the ability to stimulate ISG-transcriptional activation in a similar
manner to IFN-beta. In addition, IFN-AM was also as able to induce the expression
of the enzyme 2'-5' OAS, as did IFN-alpha. Lastly, amniotic IFN showed a
significant cross-species anti-viral activity, which was different from both
human IFN-alpha and -beta. Taken together, these data strongly suggest that IFN
AM is a novel sub-type I IFN.
PMID- 10195742
TI - Placental release of corticotrophin-releasing hormone across the umbilical
circulation of the human newborn.
AB - This study attempted to determine the placental release of corticotrophin
releasing hormone (CRH) into the umbilical circulation, and the factors which
affect it, by measuring venous and arterial levels for CRH across the umbilical
circulation in labouring as well as non-labouring elective caesarean section
patients. The relationship with measures of fetal oxygenation and acid-base
status at birth was investigated also. Forty-eight patients were studied (term
labour n = 30, term elective caesarean section n = 12, and preterm labour n = 6)
with blood sampling from a clamped segment of cord after delivery of the fetus
and from the cord at its insertion into the placenta after delivery of the
placenta, with subsequent measurement of blood gases, pH, base excess, and CRH.
For all patients, mean plasma CRH levels in the umbilical and placental vein
(115+/-13 and 145+/-18 pg/ml) were higher than those from the corresponding
artery (85+/-7 and 102+/-8 pg/ml, P<0.01 and P<0.05, respectively), indicating
placental release of CRH into the fetal compartment. In addition, placental
venous and arterial cord CRH levels were higher than those from the corresponding
umbilical levels (P<0.01 and P<0.02, respectively) indicating continued placental
release of CRH into blood within the placenta after clamping of the umbilical
circulation and delivery of the fetus. While plasma CRH levels from respective
cord vessels were all significantly higher in labouring patients at term versus
elective caesarean section patients, there were no differences compared with
preterm labouring patients. For all patients, CRH as measured in both the
umbilical and placental vein showed a modest inverse correlation to base excess
as measured in the umbilical artery, -0.31 and -0.33, respectively, both P<0.05.
It is concluded that CRH is released by the placenta into the fetal compartment
and is increased with both term and preterm labour, and with metabolic acidosis
during labour, supporting a role in the endocrine events of labour and/or
compensatory changes in uteroplacental blood flow.
PMID- 10195743
TI - Functional expressions of fms and M-CSF during trophoectodermal differentiation
of human embryonal carcinoma cells.
AB - A human embryonal carcinoma (EC) cell line, NCR-G3 (G3), is capable of
differentiating into a variety of cell types in vitro, including epithelial,
muscle, neural and trophoectodermal cells. The production of human chorionic
gonadotropin (hCG), a trophoectoderm-specific hormone, begins 7 days after
retinoic acid (RR1) treatment and peaks on day 12-13. In this study, we used G3
cells to investigate the biological significance of macrophage colony-stimulating
factor (M-CSF), also called colony-stimulating factor-1 (CSF-1), and fms, a
receptor tyrosine kinase for M-CSF. The mRNA of c-fms is constitutively expressed
in both undifferentiated and differentiated G3 cells. Immunoprecipitation with
anti-fms antibodies or flow cytometry revealed that differentiated G3 cells
express fms on the cell surface. However, we were unable to demonstrate
expression of fms on the surface of undifferentiated G3 cells. Expression of M
CSF mRNA and protein, however, was upregulated by RA treatment prior to hCG
production. In order to investigate whether expression of both molecules is
biologically functional in G3 cells, we conducted experiments using anti-M-CSF
and fms antibodies with neutralizing activity and gene transfer to achieve over
expression of fms in G3 cells. As a result, we observed that hCG production
following treatment with both neutralizing antibodies was more than 90 per cent
inhibited, and that hCG production increased significantly as a result of over
expression of fms in G3 cells. Our results enabled us to show that M-CSF and fms
play important functional roles in the differentiation of G3 cells into
trophoectoderm. G3 cells are well suited to serve as an experimental model of
human early embryogenesis and of placental differentiation.
PMID- 10195744
TI - Trophoblastic cell lines generated from tumour necrosis factor receptor-deficient
mice reveal specific functions for the two tumour necrosis factor receptors.
AB - In mice and humans, expression of the tumour necrosis factor receptor-1 (TNF-R1)
gene in placental trophoblast cells is constitutive whereas expression of the TNF
R2 gene is developmentally programmed. In order to study the individual functions
of TNF-R1 and -R2 in this lineage, cell lines were generated from placental
explants of homozygous matings of gestation day 10 outbred mice (Swiss-Webster),
TNF-R1-deficient (TNF-R1-/-) and TNF-R2-/- transgenic mice as well as the
background strain for the TNF-R2-/- mice (WT, C57BL/6x129). All of the cells
exhibited trophoblast markers; they contained cytokeratin intermediate filaments,
expressed alkaline phosphatase activity and displayed transferrin receptors, but
were negative for vimentin filaments and the macrophage marker, F4/80. Analysis
of DNA by polymerase chain reaction demonstrated the expected TNF-R genotype in
each line. In experiments testing the effects of recombinant mouse TNF-alpha
(rmTNF-alpha) on viability and proliferation of the cell lines, rmTNF-alpha
modestly but dose-dependently inhibited the growth of WT and TNF-R2-/- cells
while having no effect on TNF-R1-/- cells. Actinomycin D-treated WT and, to a
lesser extent, TNF-R2-/- cells, were more sensitive to growth inhibition than
untreated cells whereas TNF-R1-/- cell responses remained unchanged. These data
indicated that rmTNF-alpha inhibits growth of trophoblastic cells through TNF-R1
and that newly synthesized protein(s) provide partial protection against
toxicity. In contrast to the receptor species-specific effects on cell growth
exerted by rmTNF-alpha, both TNF-R mediated inhibition of alkaline phosphatase
activity. Collectively, the observations support the postulate that receptor
expression is the key factor which determines the nature and extent of TNF-alpha
effects on trophoblast cell growth and function.
PMID- 10195745
TI - Apoptotic and proliferative activities in first trimester placentae.
AB - Apoptosis and cell proliferation are widely recognized to be important
physiological processes which together maintain tissue homeostasis. The apoptotic
and proliferative processes in 38 first trimester placentae were quantified using
terminal deoxynucleotidyl transferase mediated dUTP nick end-labelling (TUNEL)
and an antibody against Ki-67 antigen, respectively. In 14 cases, the estimation
of apoptotic index was repeated with sections stained with haematoxylin and eosin
by identifying the morphological features of apoptosis. We found that the indices
obtained by either method correlated well with each other although a lower rate
was obtained with the haematoxylin and eosin stained sections. Apoptosis was
found in clusters mainly in syncytiotrophoblasts in association with fibrinoid
deposits while proliferating activity was limited to cytotrophoblasts and stromal
cells. A significant inverse correlation was observed between the proliferative
index and gestational age as well as the apoptotic index. While the extent of
apoptosis decreased with advanced gestational age, the correlation was not
statistically significant. These findings provide a potential explanation for
villous remodelling during trophoblastic invasion in early pregnancy.
PMID- 10195746
TI - The distribution of macrophages in spiral arteries of the placental bed in pre
eclampsia differs from that in healthy patients.
AB - Placental bed biopsies taken during caesarean section from 10 patients with pre
eclampsia and six healthy pregnancies were studied. We applied antibodies against
cytokeratin and different macrophage markers to analyse the distribution of
invasive extravillous trophoblast cells as compared to that of macrophages in
myometrial segments of uteroplacental arteries. The data were evaluated
quantitatively. We found a clear inverse relationship between local infiltration
with macrophages and trophoblast invasion. In pre-eclampsia, vessel cross
sections prevailed which were characterized by large numbers of macrophages but a
low degree of trophoblast invasion. In contrast, in normal third trimester
pregnancies the respective arterial segments had a high degree of trophoblast
invasion but were largely void of macrophages. These data suggest causal links
between macrophages and inhibition of intra-arterial trophoblast invasion in pre
eclampsia.
PMID- 10195747
TI - Intravascular ultrasound contrast agent: an aid in imaging intervillous blood
flow?
AB - The aim of this study was to evaluate the applicability of an intravascular
ultrasound contrast agent in examination of the uteroplacental circulation.
Uteroplacental circulation in 25 singleton third trimester pregnancies was
examined by power Doppler, first without and then with contrast agent enhancement
(Levovist, Schering AG, Germany). Eight subjects had fetal growth retardation and
17 had normal-sized fetuses. The effect of the contrast agent was evaluated using
computerized power Doppler signal intensity measurements. The Doppler signal
intensity in the uteroplacental vessels increased within 25 sec of brachial
venous injection of the contrast agent, yielding an effect which was recognizable
up to 5-8 min later. There was clear enhancement of uteroplacental flow imaging
after addition of the contrast agent in all of the examined pregnancies. The mean
percentual intensity changes after administration of the contrast agent were 33
per cent (P<0.001) in the sub-placental myometrial area and 8 per cent (P<0.001)
in the intraplacental area. No association was found between fetal growth
retardation and intensity changes or absolute intensity parameters. In
conclusion, intravascular ultrasound contrast agent facilitates imaging of the
uteroplacental circulation. It may have a valuable role in determination of
intervillous blood flow and in imaging blood perfusion in different regions of
the placenta.
PMID- 10195748
TI - Relationships between orientation of the blastocyst during implantation, position
of the chorioallantoic placenta, and vascularization of the uterus in the
noctilionoid bats Carollia perspicillata and Noctilio sp.
AB - In most eutherian mammals, the inner cell mass (ICM) of the blastocyst assumes an
almost constantly specific orientation to the uterus at the time of implantation,
and this is usually correlated with subsequent positioning of the fetal membranes
and chorioallantoic placenta. Although these relationships tend to be conserved
between closely related species, this is not the case in the noctilionoid bats.
In Carollia perspicillata, which has a simplex uterus, the ICM of the single
blastocyst becomes oriented towards the uterotubal junction on the side of
ovulation, and the discoidal placenta develops in a fundic position. In Noctilio
sp., which have partially bicornuate uteri, the ICM becomes oriented instead
towards an endometrial ridge that runs along the antimesometrial to lateral side
of the gravid horn. As development proceeds, however, the blastocyst rotates
almost 180 degrees, and the discoidal placenta eventually assumes a mesometrial
to lateral position. In these species, implantation and subsequent development of
the discoidal placenta clearly seem to be targeting major maternal vessels
supplying the uterus, rather than exhibiting a consistent pattern of orientation
relative to its mesenteric attachments. This permits their chorioallantoic
placentae to develop a dual maternal blood supply that may be essential for the
development of relatively large, precocious infants.
PMID- 10195749
TI - The need for microbicides: why aren't women's groups more involved in the fight
against AIDS?
PMID- 10195751
TI - Marked increase in anti-HIV activity, as well as inhibitory activity against HIV
entry mediated by CXCR4, linked to enhancement of the binding ability of
tachyplesin analogs to CXCR4.
AB - T22 ([Tyr5,12, Lys7]-polyphemusin II) is a strong anti-HIV compound. Six analogs
of T22 and two natural forms were synthesized. Of them, all downsized peptides
(14 residues; TW70, T131, T134, and T140) showed a higher selectivity index than
did other, 17- or 18-residue peptides. In particular, T134 and T140 showed both
lower cytotoxicity and higher antiviral activity than did T22 against HIV
infection of MT-4 cells, an HTLV-I-bearing T cell line. To clarify the inhibitory
mode of T22 and its analogs, we used a single-round replication assay (luciferase
assay), in which different envelope-bearing pseudotypes were used to infect CXCR4
or CCR5-bearing U87 cells via CD4. All of the analogs inhibited T cell line
tropic strain HXB-2 (X4) and dual-tropic strain 89.6 (R5X4) HIV infections
mediated by CXCR4, but had no effect on macrophage-tropic strain ADA (R5) or 89.6
HIV infections mediated by CCR5. The inhibition by T134 (IC50 of 2.70 nM) and
T140 (IC50 of 0.432 nM) was also stronger than that by T22 (IC50 of 5.05 nM). The
binding of anti-CXCR4 monoclonal antibody 12G5 to lymphoma-derived T cell line
Sup-T1 was more efficiently blocked by T134 and T140 than by T22. Taken together,
T22 and its analogs T134 and T140 exerted their inhibition by specific binding to
CXCR4. The marked increase in the anti-HIV activity of T134 and T140 was ascribed
to an enhancement in their ability to bind to CXCR4.
PMID- 10195750
TI - Seroepidemiological and molecular studies of human T cell lymphotropic virus type
II, subtype b, in isolated groups of Mataco and Toba Indians of northern
Argentina.
AB - We studied plasma samples from 2082 Mataco Indians living in 22 different
communities in the western part of Formosa Province, northern Argentina. Samples
were screened for HTLV-I/II antibodies by particle agglutination assay. All
positive or borderline samples were then tested by an immunofluorescence assay
(IFA) on C19 HTLV-II-producing cells. Western blot was used for confirmation of
all IFA-positive plasma samples. The crude HTLV-II seroprevalence was 3.0% (62 of
2051), and 0.9% (5 of 588) in children less than 10 years old. The latter result
suggests ongoing mother-to-child transmission, probably by breast feeding. There
was a marked increase in HTLV-II seroprevalence with age (0.9%, 0-10 years; 1.6%,
11-20 years; 4.4%, 21-30 years; 3.4%, 31-40 years; 7.2%, 41-50 years; 5.7%, >50
years) in both male (p = 0.002) and female subjects (p = 0.00002). None of the 80
non-Indian inhabitants tested was HTLV-I/II seropositive. In a second study,
among 105 Toba Indians from a village (Primavera) of the eastern part of this
region, 23 were HTLV-II seropositive with a seroprevalence of 59% in those more
than 40 years old. From seven of the Indians from Primavera, three others from
neighboring regions (including two Tobas and one Pilaga), and one intravenous
drug user (IVDU) from Rosario, DNA was extracted from peripheral blood
mononuclear cells, and the gp21 transmembrane-encoding gene (590 bp) was
amplified by PCR, cloned, and sequenced. LTR sequences were also obtained from
the Pilaga, the IVDU, and one Toba. Molecular and phylogenetic analyses revealed
that the Indians were all infected with closely related HTLV-II molecular strains
belonging to the b subtype, while the IVDU was infected with an HTLV-II subtype a
variant. Such data help to make a phylogenetic atlas of HTLV-II among Amerindian
tribes and are crucial to gain new insights into the origin and modes of
dissemination of this human retrovirus in the Americas.
PMID- 10195752
TI - Inhibition of human immunodeficiency virus type 1 replication by the K10-K42
peptide of GAP31 is due to induction of rapid but nonspecific precipitation of
viral and nonviral proteins.
AB - The 33-amino acid peptide K10-K42 has previously been described as having potent
anti-HIV-1 activity, and antiviral efficacy against hepatitis B and human
cytomegalovirus in vitro. Although the exact mechanism of antiviral activity was
unknown, it was hypothesised that the K10-K42 peptide inhibited HIV-1 by
interfering with one or more of the intracellular processes of reverse
transcription, integration, and/or viral gene expression. We performed a series
of experiments to identify and characterize the inhibitory mechanism, and to
determine whether intracellular expression of the K10-K42 peptide would
potentiate its antiviral efficacy in vitro. Surprisingly, our results revealed
that the antiviral activity of the K10-K42 peptide could be explained without
implicating intracellular inhibition of HIV-1 replication. The activity appeared
to be due to an extraordinary capacity of the K10-K42 peptide to precipitate
viral and nonviral proteins in vitro. The protein-precipitating capacity of the
K10-K42 peptide was sequence specific and a scrambled version of the 33-amino
acid peptide did not retain the activity. Although the unusual biochemical
properties of the K10-K42 peptide probably negate a number of potential
therapeutic applications, they do merit further investigation. Moreover, these
findings provide a plausible explanation of the mechanism by which the K10-K42
peptide can inhibit replication of viruses from families as genetically and
functionally diverse as Retroviridae, Hepadnaviridae, and Herpesviridae.
PMID- 10195753
TI - Lymphocyte kinetics and precursor frequency-dependent recovery of
CD4(+)CD45RA(+)CD62L(+) naive T cells following triple-drug therapy for HIV type
1 infection.
AB - New therapeutic regimens have dramatically altered morbidity and mortality
attributed to HIV-1 infection. Changes in lymphocyte subsets after treatment may
mirror salutary clinical changes. Over 4 months we analyzed lymphocyte subsets in
20 patients starting new HIV-1 therapy. Absolute numbers of lymphocytes, CD4+ T
cells, CD8+ T cells, and B cells increased significantly by 4 months, but CD8+ T
cell and B cell increases were restricted to late-stage patients. Subset analysis
revealed that the magnitude of recovering naive-phenotype CD4+ T cells (slope)
correlated with the number of these cells present at baseline, equaling or
exceeding the memory-phenotype slope within days if these naive cells were
abundant at baseline. Five of 10 patients in whom naive-phenotype CD4+ T cells
were absent at baseline partially repopulated these cells by 4 months. These
findings have important implications for the origin and mechanisms of renewal of
naive-phenotype CD4+ T cells following effective treatment for HIV-1 infection.
PMID- 10195754
TI - Viremia and AIDS in rhesus macaques after intramuscular inoculation of plasmid
DNA encoding full-length SIVmac239.
AB - We have succeeded in stably maintaining the entire genome of SIVmac239 as a
plasmid clone. Supercoiled proviral plasmid DNA was inoculated intramuscularly
into two adult rhesus macaques and into a neonate. All three animals became
viremic and seroconverted. Viral kinetics were followed prospectively by
quantitative competitive reverse transcriptase polymerase chain reaction (QC-RT
PCR), measurement of proviral DNA load in peripheral blood mononuclear cells
(PBMCs) by PCR, and virus isolation by cocultivation. The infant developed high
virus loads and succumbed to AIDS and SIV-associated nephropathy at 10 weeks
postinoculation. Both adults are still living but have progressed to AIDS; one
adult has also developed severe thrombocytopenia. We conclude that infection
through intramuscular inoculation of cloned plasmid DNA encoding the entire
proviral genome is reproducible and will provide a useful tool for studying viral
pathogenesis.
PMID- 10195755
TI - Antigenicity and immunogenicity of the V3 domain of HIV type 1 glycoprotein 120
expressed on the surface of Streptococcus gordonii.
AB - Five different V3 domains of HIV-1 gp120 were expressed on the surface of the
gram-positive bacterium Streptococcus gordonii, a model live vector for vaccine
delivery. Sera of HIV-1-infected individuals and human monoclonal antibodies
specifically recognized the gp120 sequences on the bacterial surface. Recombinant
V3 from the reference HIV-1 strain MN was also shown to retain a conformation
that allowed reaction with a conformation-specific monoclonal antibody. A V3
specific serum antibody response was detected in mice immunized both by
subcutaneous injection and by vaginal colonization. V3-specific IgG2a antibodies,
suggestive of a Th1 response, were found in the sera of mice colonized by
recombinant bacteria.
PMID- 10195756
TI - CD8+ lymphocyte antiviral activity in monkeys immunized with SIV recombinant
poxvirus vaccines: potential role in vaccine efficacy.
AB - Protection against intravenous simian immunodeficiency virus (SIV) challenge was
assessed in rhesus macaques after immunization with a highly attenuated vaccinia
(NYVAC)-SIV recombinant. One-third of vaccinated animals controlled viral
infection and progressed to disease more slowly than control animals (Benson J,
et al.: J Virol 1998;72:4170). However, this protection was not associated with
neutralizing antibodies, cytotoxic T lymphocytes, or helper T cell responses. To
explore other potential correlates of protection, we examined CD8+ T cell
antiviral activity in macaques vaccinated with NYVAC-SIV, with or without added
cytokine adjuvants, and in controls receiving only IL-12 or IL-12 plus IL-2.
Before immunization, naive macaques exhibited a broad range of CD8+ T cell
antiviral activity. Nevertheless, in the course of immunization, the vaccinated
macaques as a group developed increased CD8+ T cell antiviral activity while the
controls remained stable. Infectious SIV exposure also increased antiviral
activity. Prechallenge antiviral activity levels of vaccinated macaques were not
sufficient to prevent SIV transmission or control viral replication during acute
infection. However, vaccinated animals consistently exhibited reduced viral loads
postchallenge compared with controls. Moreover, high suppressive activity 8 weeks
postchallenge, at which time the viremia set point was established, was
significantly correlated with reduced viral load and slow disease progression.
Prechallenge antiviral activity influenced this result, as decreased viremia and
slow progressor status were more apparent in macaques with high suppressive
activity both pre- and postchallenge. Our data demonstrate the impact of CD8+
antiviral activity on viral replication and disease progression, and suggest that
vaccine designs able to elicit high levels of this activity will contribute
significantly to protective efficacy.
PMID- 10195757
TI - Involvement of microglia in cerebrospinal fluid glutamate increase in SIV
infected rhesus monkeys (Macaca mulatta).
AB - Cerebrospinal fluid (CSF) samples were collected from 24 uninfected and 24 SIV251
MPBMC-infected rhesus monkeys during early infection and from 6 animals in a
longitudinal design up to 7 months postinfection to investigate excitatory and
inhibitory amino acid neurotransmitter levels. During the early infection period
CSF amino acid concentrations of infected animals were not significantly
different from those of uninfected animals. However, long-term studies
demonstrated that gamma-aminobutyric acid (GABA) concentrations were decreased
while glutamate concentrations were increased late in infection compared with the
preinfection values of the same animals. Moreover, we showed that the source of
increased glutamate in animals with AIDS is, at least partially, microglial
cells. Our data support the hypothesis that excitotoxicity is involved in
immunodeficiency virus-induced neurological disease and propose microglia as a
contributor to excitotoxic damage.
PMID- 10195758
TI - Species-specific changes in the CCR5 gene from African and Asian nonhuman
primates.
PMID- 10195759
TI - DNA sequence of the long terminal repeat of human immunodeficiency virus type 1
subtype A through G.
PMID- 10195760
TI - Role of peripheral blood mononuclear cell subsets of seronegative donors in HIV
replication: suppression by CD8+ and CD16+ cells and enhancement by CD14+
monocytes.
PMID- 10195761
TI - Rotavirus serotype G5: an emerging cause of epidemic childhood diarrhea.
PMID- 10195762
TI - Interferon gamma production during bovine respiratory syncytial virus (BRSV)
infection is diminished in calves vaccinated with formalin-inactivated BRSV.
AB - Formalin-inactivated respiratory syncytial virus (FI-RSV) vaccination has been
associated with severe disease in humans. Research in mice suggests that FI-RSV
may prime for decreased interferon gamma (IFN-gamma) production at subsequent
infection. Interferon-gamma production by peripheral blood mononuclear cells
(PBMC) was measured following challenge of calves vaccinated with FI-BRSV to
determine whether a similar mechanism is operative in a host naturally
susceptible to RSV. Eight-week old male Holstein calves were administered FI-BRSV
and mock challenge (V/M, n = 6); mock vaccination and BRSV challenge (M/C, n = 6)
or FI-BRSV and BRSV challenge (V/C, n = 7). Vaccine was administered twice at a 2
week interval; challenge followed one month later. On days 0, 5 and 10
postchallenge (PC), PBMC were stimulated in vitro for 24 h with live BRSV,
concanavalin A (positive control) or spent media (negative control). Supernatants
were assayed for IFN-gamma using ELISA. Interferon-gamma production by BRSV
stimulated PBMC was increased in M/C and V/C calves as compared to V/M calves on
day 5 PC (p < 0.015); and increased in M/C calves compared to V/C and V/M calves
on day 10 PC (p < 0.015). Over time postchallenge, a significant increase in IFN
gamma production by BRSV-stimulated PBMC was seen in M/C calves (p < 0.025) but
not in V/C calves. FI-BRSV vaccination of calves led to diminished IFN-gamma
production postchallenge. Decreased IFN-gamma production may have contributed to
impaired viral clearance and enhanced disease in FI-BRSV vaccinated calves.
PMID- 10195763
TI - Long-term protection of mice against Leishmania major with a synthetic peptide
vaccine.
AB - A single synthetic T cell epitope (PT3), obtained from the histidine zinc-binding
region of the metalloprotease gp63, was employed in a vaccine trial using two
virulent strains of L. major. When a single subcutaneous injection of PT3 was
delivered with the Thl stimulating adjuvant poloxamer 407, BALB/c mice were
protected for at least 10 months against the disease. Vaccinated mice were
largely free of lesions on termination of the experiment. Protection was similar
for both L. major MRHP/SU/59 Neals and L. major WHOM/IR/-/173 strains which
manifest different disease sequelae. Thus, these data provide evidence that a
single subcutaneous injection of a single synthetic T cell epitope is sufficient
to provide long-lasting protection against two highly virulent strains of L.
major in BALB/c mice.
PMID- 10195764
TI - Immunogenicity of IRIV- versus alum-adjuvanted diphtheria and tetanus toxoid
vaccines in influenza primed mice.
AB - The immunogenicity and protectivity of two different toxoid vaccines were
compared in mice. In one formulation, toxoids (diphtheria or tetanus) were
adsorbed to alumoxid, whereas in the other formulation the toxoids were
crosslinked to immunopotentiating reconstituted influenza virosomes (IRIVs). A
preimmunization with influenza antigens is necessary for a good anti-toxoid
antibody response when the IRIV formulation was administered. After two
immunizations with the IRIV- or alum-based vaccines, the IRIV-based formulation
induced a higher humoral immune response than toxoids adsorbed to alum. Using an
in vitro test, diphtheria toxin neutralizing antibodies were tested. Di-IRIV
induced a significantly (p = 0.002) higher titer of diphtheria toxin neutralizing
antibodies than Di-alum. Tetanus challenge experiments showed, that the IRIV
based tetanus vaccine induced a threefold higher titer of protective antibodies
than the tetanus toxoid adsorbed to alum. Therefore, the IRIV-based formulations
appeared to be superior to the alum-based vaccines in terms of immunogenicity and
protectivity.
PMID- 10195765
TI - A cost benefit analysis of routine varicella vaccination in Spain.
AB - The objective of the study was to assess varicella epidemiology and the cost of
disease in Spain, in order to perform a cost benefit analysis of universal
vaccination at 15 months of age. Epidemiological data were obtained from a survey
of 150 children with varicella, from hospitalizations and from the Spanish
literature. A Markov decision tree was designed with two alternatives,
vaccination or nonvaccination. Direct costs derived from the disease were lower
than the cost of vaccination (ratio 0.54:1), however when indirect costs, such as
working time loss were taken into account, vaccination was the best alternative,
with a saving of P(T)2627 per vaccinated subject (P(T)1.6 recovered per peseta
invested in the program). Sensitivity analysis shows that decreasing vaccine
coverage and efficacy to 0.7, increasing the annual discount rate to 20% and with
a vaccine price less than P(T)6000, vaccination is always the best alternative.
In conclusion, from the economic point of view, a universal varicella vaccination
program in children at 15 months of age would be justified in Spain.
PMID- 10195766
TI - Induction of protective immunity against Dengue virus type 2: comparison of
candidate live attenuated and recombinant vaccines.
AB - Dengue (DEN) viruses (serotypes 1 to 4) are mosquito-borne flaviviruses which
cause about fifty million human infections annually and represent an expanding
public health problem in the tropics. At present, there are no safe and effective
vaccines which induce protective immunity to all four serotypes of DEN. Natural
infection or vaccination with native and recombinant proteins may induce an
immune response to the surface envelope E-protein which was shown to be
protective to super-infection with homologous serotype of the virus. Purified
recombinant E-protein was made in the baculovirus-Spodoptera frugiperda
expression system. This protein induced neutralizing antibodies in mice. These
results prompted us to immunize cynomolgus monkeys (Macaca fascicularis) with
either a live attenuated DEN-2 vaccine or the recombinant E-protein complexed to
aluminum hydroxide. After immunization, the monkeys were challenged with the
homologous DEN virus. Serum was collected at several time points and a virus
specific antibody response including a virus neutralizing antibody response was
measured. Antibody kinetics and levels were similar to those recorded in humans
with a natural DEN-virus infection. Virus isolation and type specific RT-PCR were
performed on the serum samples. The virus was isolated from sham vaccinated
control monkeys but not from monkeys vaccinated with the live attenuated vaccine.
One of the two monkeys immunized with the recombinant E-protein was also
protected. Taken together these data indicate the potential of both candidate
vaccines and stress the need for evaluation of different antigen presentation
systems for the development of a subunit vaccine approach for DEN.
PMID- 10195767
TI - Antigenic drift in swine influenza H3 haemagglutinins with implications for
vaccination policy.
AB - In order to explore the occurrence of antigenic drift in swine influenza A(H3N2)
virus, we examined virus strains from outbreaks of respiratory disease among
finishing pigs in the Netherlands in 1996 and 1997 and from earlier outbreaks. In
contrast to swine H3N2 strains from the 1980s, the recent isolates did not show
significant cross-reactivity with human influenza A(H3N2) viruses from 1972-1975
in haemagglutination inhibition tests. These new strains form a separate branch
in the phylogenetic trec of the HA1 parts of HA. We conclude that recently there
has been considerable antigenic drift within the swine H3N2 viruses in the
Netherlands and Belgium and recommend replacement of the A/Port Chalmers/1/73
(H3N2) strain in the current vaccine by a more recent swine H3N2 isolate.
PMID- 10195768
TI - The influence of host factors and immunogenetics on lymphocyte responses to
Hepagene vaccination.
AB - We have shown that both demographic and immunogenetic factors are involved in the
immune responses of Hepagene vaccinated individuals who were persistent
nonresponders to 'S' containing hepatitis B vaccines. The HLA-DRB1 0701; DQB1
0202 genotype was found to be associated with a decline of anti-HBs antibodies
(anti-HBs) and were frequent in those individuals who remained nonresponders
following booster vaccination. Contrary to previously published 'S' vaccination
data, Hepagene stimulated T-cell responses showed a lack of correlation with the
humoral responses. Limiting dilution analysis demonstrated that the cellular
immune response is associated with the kinetics of exposure to Hepagene rather
than magnitude of the anti-HBs response. It remains that despite the inclusion of
the pre-S proteins 74% nonresponder vaccinated individuals failed to produce >
100 IU/l of anti-HBs. However, these were persistent nonresponders and it was
therefore encouraging that two doses of Hepagene did seroconvert (> 10 IU/L) 61%
of this difficult group.
PMID- 10195769
TI - Recombinant vaccinia viruses and gene gun vectors expressing the large subunit of
Schistosoma mansoni calpain used in a murine immunization-challenge model.
AB - Schistosomiasis is a parasitic disease affecting over 200 million people every
year in tropical regions of the world. Drug treatment and other existing control
measures are costly and have failed to eliminate the incidence of infection,
morbidity and mortality due to Schistosoma mansoni infection. Vaccination of
susceptible individuals using recombinant vaccines encoding key S. mansoni
antigens may be the most effective and least expensive means of controlling
schistosomiasis. A candidate vaccine antigen is p80, the large subunit of the S.
mansoni protease, calpain. In our vaccine studies, we have employed both the wild
type p80 and a mutant p80 (mut p80) in which an active site amino acid was
genetically altered to create a less proteolytically-active enzyme. Two vaccine
delivery approaches were implemented using p80 or mut p80 as vaccine antigen:
recombinant vaccinia virus (RVV) inoculation and DNA immunization via the Accell
gene gun (GG) delivery system. RVV's expressing p80 and mut p80 were generated
and tested for recombinant protein expression in vitro. These RVV's were tested
for protective capacity in mouse challenge studies. Neither subcutaneous nor
intranasal vaccinations with RVV-p80 or RVV-mut p80 were capable of significantly
reducing the mean worm burdens of vaccinated mice. A GG-RVV combination
immunization regime using WRG-vectors encoding p80 and mut p80 for GG priming and
the RVV's for boosting prior to S. mansoni challenge infection was performed and
no significant protection was obtained over two repeated studies. However,
duplicate challenge studies involving GG immunization of mice with WRG-vectors
encoding p80 or mut p80 revealed that 3 inoculations of mice with WRG-full5' mut
p80 (containing the full 5' untranslated region of mut p80) provided 60%
protection which was statistically significant (p < 0.05). These preliminary in
vivo studies demonstrate the potential for further study of the protection
afforded by gene gun-delivered WRG-full5' mut p80 into subsequently-challenged
mice. Such studies may pave the way to effective vaccination of humans using WRG
DNA vectors expressing a schistosomal calcium-activated neutral protease.
PMID- 10195770
TI - ISCOM vaccine induced protection against a lethal challenge with a human H5N1
influenza virus.
AB - Recently avian influenza A viruses of the H5N1 subtype were shown to infect
humans in the Hong Kong area, resulting in the death of six people. Although
these viruses did not efficiently spread amongst humans, these events illustrated
that influenza viruses of subtypes not previously detected in humans could be at
the basis of a new pandemic. In the light of this pandemic threat we evaluated
and compared the efficacy of a classical non-adjuvanted subunit vaccine and a
vaccine based on immune stimulating complexes (ISCOM) prepared with the membrane
glycoproteins of the human influenza virus A/Hong Kong 156/97 (H5N1) to protect
roosters against a lethal challenge with this virus. The ISCOM vaccine induced
protective immunity against the challenge infection whereas the non-adjuvanted
subunit vaccine proved to be poorly immunogenic and failed to induce protection
in this model.
PMID- 10195771
TI - Analysis of the ability of five adjuvants to enhance immune responses to a
chimeric plant virus displaying an HIV-1 peptide.
AB - The ability of five different adjuvants (alum, complete Freund's adjuvant, Quil
A, AdjuPrime and Ribi) to stimulate humoral and T-cell mediated immune responses
against a purified chimeric virus particle was investigated. Each adjuvant was
administered subcutaneously to adult mice together with 10 microg of wildtype
(wt) cowpea mosaic virus (CPMV) or a chimeric CPMV displaying the HIV-1 gp41
peptide, residues 731-752. All preparations elicited strong antibody responses to
CPMV, but Quil A elicited the highest and most consistent responses to the HIV-1
peptide. This finding was reflected in both ELISA titres with immobilized peptide
and in HIV-1-neutralizing antibody. In addition Quil A was also, the only
adjuvant to stimulate an in vitro proliferative T-cell response. Surprisingly
with all adjuvant formulations a predominately IgG2a anti-gp41 peptide response
was observed, indicating a type 1 T-helper cell-like response. Furthermore, the
efficiency of the CPMV display system was demonstrated by its ability to induce
good levels of peptide specific antibody in the absence of any adjuvant.
PMID- 10195772
TI - Expression of interleukin-2 (IL-2) receptor alpha and CD45RO antigen on T
lymphocytes cultured with measles virus antigens, compared with humoral immunity
in measles vaccinees.
AB - In response to two types of measles virus (MV) antigens, a vaccine strain CAM and
a wild strain isolated in 1994, the expression of IL-2 receptor alpha
(CD25)(+)CD45RO(+)CD4(+) T-lymphocytes (T-cell activation) was analyzed by flow
cytometry. In 75 healthy subjects with measles hemagglutination inhibition tests
> or =1:16, the percentage of T-cell activation was significantly increased
compared with that in seronegative individuals (p) < 0.05). Moreover, the T-cell
expression was not significantly different among the vaccinated (n = 38), the
naturally infected (n = 28) and the subclinically infected (exposed with wild
type without history of measles infection and HI titers > or =1:16) (n = 10)
groups. T-cell activation stimulated with MV antigens and HI antibody titers
persisted for almost 30 years in the vaccinated group. These results suggest that
cell-mediated immunity persists for long periods after vaccination and does not
be influenced by antigenic drift.
PMID- 10195773
TI - Immunoadjuvant action of plasmid DNA in liposomes.
AB - Bacterial DNA and oligodeoxynucleotides containing immunostimulatory sequences
with a CpG motif stimulated a Th1 type response in vivo. The adjuvant action of a
non-coding plasmid DNA derived from pRc/CMV HBS (encoding the S region of
hepatitis B surface antigen, HBsAg) in mice was investigated. The role of
methylation on the adjuvanticity of the plasmid as well as the effect of vaccine
formulation employed on the outcome of antigen-specific humoral and cellular
responses were also studied. The results demonstrated that plasmid DNA acted as a
Th1 promoting adjuvant when mixed as such or co-entrapped in liposomes with a
very low dose of antigen. However, the adjuvant activity was lost when separate
liposome entrapped formulations of both the antigen and the plasmid DNA were
mixed, indicating a necessity for the antigen and the plasmid DNA to contact the
same APC for optimal immune activation. A decreased adjuvanticity of plasmid DNA
upon methylation with HpaII methyltransferase was also demonstrated. A mechanism
that may help partially explain the reduction in adjuvanticity after modification
of C residues is also discussed.
PMID- 10195774
TI - Safety and immunogenicity of combined diphtheria-tetanus-pertussis (whole cell
and acellular)-Haemophilus influenzae-b conjugate vaccines administered to
Indonesian children.
AB - A randomized double-blind trial was conducted to evaluate the safety and
immunogenicity of vaccines comprised of diphtheria (D) and tetanus (T) toxoids
combined with either a whole cell (P) or an acellular (aP) pertussis component
and Haemophilus influenzae type b polyribosylphosphate (PRP) tetanus toxoid
conjugate (PRP-T) in Indonesian infants. Three doses of either DTaP, DTaP-PRP-T,
or DTP-PRP-T were administered to 930 infants approximately 2-3 months of age and
at 2 month intervals thereafter. A booster dose of either DTP-PRP-T or DTaP-PRP-T
was administered at 15-18 months of age. Both local and systemic reactions
occurred at a significantly (p < 0.001-0.026) higher rate in the group that
received whole cell pertussis vaccine versus groups which were immunized with aP
containing vaccines. There was no significant difference (p > 0.05) in the rate
of adverse events between groups immunized with DTaP or DTaP PRP T. One month
after the third dose of vaccine, 99% of subjects had achieved > or =0.1 IU of
anti-D and anti-T antibody per ml of serum. The geometric mean titer (GMT) to D
was significantly (p < 0.001) higher in the group immunized with DTaP versus the
other two groups whereas the anti-T GMT was significantly (p < 0.006) higher for
the group immunized with DTP-PRP-T. Both the anti-pertussis toxin (PT) and anti
filamentous hemagglutinin (FHA) antibody levels were significantly (p < 0.001)
higher in recipients of acellular versus whole cell pertussis vaccine. In
contrast, the anti-B. pertussis agglutinating antibody response was significantly
(p < 0.0001) higher in the group immunized with whole cell pertussis vaccine. The
anti-PRP GMTs (microg antibody/ml) at 7 months were 0.096, 3.35 and 6.11 for
groups immunized with DTaP, DTaP-PRP-T and DTP-PRP-T, respectively. The GMT for
those immunized with DTP-PRP-T was significantly (p < 0.001) higher compared to
recipients of DTaP-PRP-T. The percent of children who attained > or =0.15 or > or
=1 microg/ml after immunization was 18 and 2% for the DTaP group, 93 and 76% for
the DTaP-PRP-T group and 97 and 88% for the DTP-PRP-T group. At the > or =1
microg/ml level the difference between the DTaP-PRP0-T and DTP-PRP-T groups was
significant (p < 0.01). Children immunized with either DTaP, DTaP-PRP-T, or DTP
PRP-T were reimmunized with DTaP-PRP-T whereas a portion of children immunized
with DTP PRP T where also boosted with this vaccine at 15-18 months of age. There
was a vigorous anamnestic response to the D and T components with all children
possessing > or =0.1 IU/ml. There was also a substantial increase in anti-PT,
anti-FHA and B. pertussis agglutinating antibodies. The poorest anti-PT response
was seen among children receiving DTP-PRP-T for both primary and reimmunization
while the highest agglutinating antibody response followed receipt of 4 doses of
DTP-PRP-T. Greater than 80% of children immunized with either DTP PRP T or DTaP
PRP-T possessed > or =0.15 microg/ml before boosting versus 38% for those
vaccinated with DTaP (p < 0.001). Primary immunization with DTP-PRP-T resulted in
a significantly (p < 0.05) higher percentage (72%) maintaining > or =1 microg/ml
compared to those immunized with DTaP-PRP-T (46%). Prior to reimmunization, the
anti-PRP GMT was significantly (p < 0.005) higher for children immunized with 3
doses of DTP-PRP-T versus DTaP-PRP-T. Subsequent to reimmunization, > or =95% of
subjects attained > or =1 microg/ml.
PMID- 10195775
TI - Oral immunization with recombinant Helicobacter pylori urease confers long
lasting immunity against Helicobacter felis infection.
AB - Recombinant Helicobacter pylori urease (rUre) has been shown to confer protection
against challenge with Helicobacter felis in mice. The purpose of the present
study was to examine duration of the immune response and long-term protective
efficacy of immunization with rUre. Swiss Webster mice were orally immunized four
times at weekly intervals with 100 microg rUre plus 5 microg heat-labile
enterotoxin of Escherichia coli (LT) adjuvant, or with LT only. At 4, 10, 20 or
40 weeks post immunization, 25 rUre-immunized mice and control mice were
challenged with H. felis and sacrificed at 2 or 10 weeks post-challenge. H. felis
infection was assessed by gastric urease assay and by histology. Anti-H. pylori
urease specific antibody levels were measured in serum and saliva both pre- and
post-challenge. Over the 40 week time period, the infection rates in rUre
immunized mice were significantly lower than those in controls (p < 0.05) as
assessed by gastric urease activity. Protection ranged from 79 100% at 2 weeks
post-challenge and 63-78% at 10 weeks post-challenge. Gastric bacterial density
in rUre-immunized mice was significantly lower than that of controls (p < 0.03)
as determined by histologic assessment. Anti-urease antibody levels remained
elevated in the serum and mucosal compartments at 39 weeks following
immunization. This study shows that immunization with rUre plus LT results in
long-lasting protective immunity against challenge with H. felis.
PMID- 10195776
TI - Optimal induction of upper respiratory tract immunity to reovirus 1/L by combined
upper and lower respiratory tract inoculation.
AB - There has been an increasing interest in developing vaccines which are both easy
to administer and which elicit functionally protective immune responses at
mucosal and/or systemic sites. Intranasally administered vaccines meet the
criteria of ease of administration and are thought to stimulate respiratory
mucosal immunity via interaction with nasal associated lymphoid tissues (NALT).
The aim of this study was to gain a better understanding of how best to stimulate
respiratory-mucosal immunity using a murine model of respiratory reovirus
infection. Either a predominantly upper respiratory tract infection or a
combination upper and lower respiratory tract infection was established by
administering the same virus dose in either a small or large inoculum volume.
These studies demonstrate that stimulation of NALT alone by an upper respiratory
tract infection does not induce an optimal primary antibody response even in the
nasal cavity. Effective immunity of both the upper and lower respiratory tract
was obtained when a combination upper and lower respiratory tract infection was
established. These results have important clinical implications since they
suggest that effective respiratory mucosal immunity will be best achieved by the
combined stimulation of both the upper and lower respiratory tract and will
likely require both intranasal as well as inhaled aerosol delivery of antigen to
the lower respiratory tract in humans.
PMID- 10195777
TI - The two amino acid substitutions in the L protein of cpts530/1009, a live
attenuated respiratory syncytial virus candidate vaccine, are independent
temperature-sensitive and attenuation mutations.
AB - cpts530/1009 is a live-attenuated, temperature-sensitive (ts) RSV vaccine
candidate that was shown previously to be attenuated for seronegative humans. It
was generated by two rounds of chemical mutagenesis: first, a partially
attenuated, cold-passaged (cp), non-ts RSV mutant (cpRSV) was mutagenized to
yield the ts derivative cpts530, and then cpts530 was mutagenized to yield
cpts530/1009, which is more ts. Previous nucleotide (nt) sequence analysis of
cpts530 showed that it has a single nt change compared to cpRSV that results in
an amino acid substitution at residue 521 in the L protein. Reverse genetics
confirmed that this mutation is responsible for the ts phenotype of cpts530.
Here, determination of the complete 15,222-nt sequence of cpts530/ 1009
identified a single change compared to cpts530, namely a point mutation at nt
12002, which results in a methionine-tovaline substitution at amino acid 1169 in
the L protein. The contribution of the 1009 mutation to the level of temperature
sensitivity and attenuation exhibited by cpts530/1009 was evaluated by its
introduction alone or with the 530 and cp mutations into the full-length cDNA
clone of wild-type (wt) RSV. Subsequent analysis of infectious viruses recovered
from the mutant cDNAs indicated that (i) the 1009 mutation indeed was a ts
mutation and the level of temperature sensitivity specified by the 1009 mutation
was less than that specified by the 530 mutation, (ii) the 530 and 1009 mutations
each contributed to attenuation in the upper respiratory tract of mice and their
effects were additive, (iii) viruses bearing the 1009 mutation were more
attenuated in the lower respiratory tract of mice than viruses bearing the 530
mutation and (iv) the combination of the 530 and 1009 mutations in the cpRSV
background resulted in the same level of temperature sensitivity and attenuation
in mice as that observed for the biologically-derived cpts530/1009 mutant. These
data show that the genetic basis of the attenuation and temperature sensitivity
of the cpts530/1009 candidate vaccine virus is the sum of the contributions of
seven identified amino acid substitutions, i.e. the 5 cpRSV mutations, the 530
mutation and the 1009 mutation.
PMID- 10195778
TI - Mucosal administration of a chimera composed of Pseudomonas exotoxin and the
gp120 V3 loop sequence of HIV-1 induces both salivary and serum antibody
responses.
AB - We have used a mouse immunization model to evaluate the potential for a chimera
protein composed of a nontoxic form of Pseudomonas exotoxin (ntPE) to incite and
sustain a mucosal immune response against an integrated antigen. The chimera,
termed ntPE-V3MN26, contained 26 amino acids of the gp120 V3 loop region sequence
of the MN strain of HIV-1 integrated in place of the Ib region of ntPE. Following
either vaginal, rectal, oral or subcutaneous administration and boosting, anti
gp120-specific IgA and IgG levels in serum and saliva samples were assessed by
ELISA. All dosing regimens stimulated significant and comparable salivary IgA and
serum IgG responses at 1, 2 and 3 months after the initial inoculation. Following
a boost at 16 months with ntPE-V3MN26, a strong memory response to the antigen
was observed. Isotyping of serum antibodies at this time suggested that both a
Thl and a Th2 response had been induced. Responses to ntPE-V3MN26 following
subcutaneous injection in the presence or absence of Freund's adjuvant
demonstrated that Freund's adjuvant resulted in a three-fold greater enhancement
of immune response compared to administration of chimera alone. These results
demonstrate that mucosal presentation of a chimera composed of a nontoxic form of
Pseudomonas exotoxin can result in a strong mucosal and systemic antigen-specific
immune response to an integrated antigen. The profound memory responses induced
by this chimera may be particularly useful for practical vaccine applications.
PMID- 10195779
TI - Recognition of HIV-derived B and T cell epitopes displayed on filamentous phages.
AB - The amino acid sequence of HIV reverse transcriptase (RT) from residue 248 to
residue 262 was expressed on the surface of filamentous phage fd, fused to the
major coat protein gVIIIp. The chimeric phage was used to assess the ability of
anti-RT (248-262) human T cell lines and clones to become activated by the phage
displayed peptide. The RT peptide displayed on phage was recognized by the T
cells and induced production of Abs. However, not all T cells raised against the
synthetic RT (248-262) peptide could respond. Lack of recognition did not depend
on differences in the ability of different APCs to present the phage, but was
apparently determined by the TCR specificity. The results presented here may be
relevant to the design of recombinant protein-based subunit vaccines.
PMID- 10195780
TI - Novel modifications to the C-terminus of LTB that facilitate site-directed
chemical coupling of antigens and the development of LTB as a carrier for mucosal
vaccines.
AB - To facilitate site-directed chemical coupling of antigens to the heat labile
enterotoxin B subunit of Escherichia coli (LTB), a series of genetically modified
fusion proteins of LTB were constructed. The LTB fusion proteins had modified
versions of a short (14 amino acid) spacer epitope called the Pk tag attached at
their C termini. The LTB-Pk.cys mutants differed from each other in the position
of a single cysteine residue within the Pk tag. The presence of a cysteine
residue at any position within the Pk spacer tag did not prevent the LTB-Pk.cys
proteins from forming pentamers or binding to GM1 gangliosides, but the position
of the cysteine had variable impact on the yield of the fusion proteins.
Following site-directed chemical coupling of antigens to the cysteine residue
within the Pk tag, the LTB antigen conjugates retained their ability to bind GM1
on the surface of eukaryotic cells. Intranasal immunisation of mice with an
experimental antigen (HRP) chemically linked to LTB-Pk.cys induced high levels of
anti-HRP antibodies that could be detected in the serum, saliva and nasal and
lung washes. No antibody responses to HRP were detected when HRP was co
administered with, but not linked to, LTB-Pk.cys.
PMID- 10195781
TI - A novel epitope R7V common to all HIV-1 isolates is recognized by neutralizing
IgG found in HIV-infected patients and immunized rabbits.
AB - We have previously reported that the presence of antibodies (Ab) directed to the
beta2-microglobulin-derived peptide R7V in patient's serum correlated with the
nonprogression to AIDS. In order to investigate whether R7V motif could represent
a potential target for neutralization, we have immunopurified anti-R7V Ab from
sera of nonprogressors, as well as from sera of rabbits injected with R7V. We
showed that human as well as rabbit purified,anti-R7V IgG precipitated laboratory
adapted strains, as well as primary isolates from different clades indicating
that: (1) R7V epitope is a common motif presented at the surface of genetically
divergent HIV-1 strains (2) R7V is immunogenic in vivo. When used in neutralizing
assay, purified anti-R7V Ab from human or rabbit origin were shown to neutralize
infection by HIV-1 laboratory adapted strains and HIV-1 primary isolates. All
together, our results indicate that the R7V motif shared by all HIV strains could
be considered as a possible candidate for an HIV vaccine.
PMID- 10195782
TI - Identification of an active Chi recombinational hot spot within the HIV-1
envelope gene: consequences for development of AIDS vaccines.
AB - Because of a sequence similarity between the HIV-1 envelope glycoprotein gp120
and the variable region of human immunoglobulins, we have suggested that the use
of this protein as a vaccine component could strongly influence the host immune
system, making it more vulnerable to HIV, and in the long term, accelerate
disease progression in asymptomatic HIV patients. Using a chimeric primer
consisting of the nucleotide sequence derived from the HIV-1 env gene coding for
the second conserved region of gp120, and the highly conserved sequence derived
from the human immunoglobulin gene coding for the V(H)III domain, we have
identified in sera of AIDS patients HIV-1 field isolates carrying the complete
and active Chi recombinational hot spot (GCTGGTGG). We have also demonstrated in
vivo recombination between the HIV-1 gene coding for the central portion of the
gp120 involving the V3 loop and the bacterial gene coding for the clp protease.
These results strongly support and reinforce the previous contention and the
serious concern that AIDS vaccine candidates carrying the HIV-1 env gene on viral
and bacterial vectors, could result in the generation of new pathogens with
unpredictable effects on the immune system.
PMID- 10195783
TI - Concurrent administration of inactivated hepatitis A vaccine with immune globulin
in healthy adults.
AB - 301 healthy adult volunteers were randomized to one of three treatment groups:
inactivated hepatitis A vaccine alone; inactivated hepatitis A vaccine with
immune globulin (Ig) concurrently; or Ig alone. The first two treatment groups
received a second dose of hepatitis A vaccine at week 24. Anti-HAV was measured
4, 8, 12, 24 and 28 weeks after the primary immunization. When comparing subjects
receiving inactivated hepatitis A vaccine alone to those receiving vaccine and
Ig, the seropositivity rates were not significantly different at 4, 8, 12 and 28
weeks, but at week 24 the seropositivity rate was lower in the group receiving
both vaccine and Ig compared to the group receiving vaccine alone (92.0% compared
to 97.0%). At weeks 8, 12 and 24 the geometric mean titers (GMTs) were
significantly lower for subjects receiving both vaccine and Ig. The GMTs were not
significantly different after the second dose of vaccine. At all time points, the
lower serum antibody concentrations observed in subjects receiving both
inactivated hepatitis A vaccine and Ig were nevertheless substantially higher
than the cutoff for assay seropositivity and much higher than after Ig alone;
these differences are therefore clinically insignificant.
PMID- 10195784
TI - A new method of non-cross-linking conjugation of polysaccharides to proteins via
thioether bonds for the preparation of saccharide-protein conjugate vaccines.
AB - Bacterial polysaccharides, including capsular polysaccharides, are poor
immunogens particularly in young infants. However, conjugation of bacterial
polysaccharides to immunogenic carrier proteins generally results in conjugates
that induce strong antipolysaccharide T-helper-cell dependent immune responses,
also in young infants. The magnitude of the response and the extent of the T
helper-cell dependency is related to the chemical characteristics of the
particular conjugate such as presence or absence of polysaccharide-protein cross
linking, presence or absence of spacer arms, character of spacer arms, type of
carrier protein, size of conjugated polysaccharide hapten and molar degree of
substitution. In the present study a new, general and simple method for the
preparation of poly- and oligosaccharide-protein conjugates is presented. This
new method is based on spacer-introducing chemistry that allowed for conjugation
of a model polysaccharide, dextran, ranging in size from 0.5 to 150 kDa, to
tetanus toxoid (TTd). The developed conjugation method involves derivatization of
polysaccharide with 2-iminothiolane (2-IT) and activation of carrier protein,
such as TTd, with N-hydroxysuccinimide ester of bromoacetic acid. Reaction rates
and accordingly the substitution of the conjugates, could be controlled by
varying time, pH and concentration of the reactants. Unlike direct reductive
amination, the 2-IT based conjugation technology is fast and made it possible to
couple fairly large polysaccharides to TTd.
PMID- 10195785
TI - Inhibitory effect of trehalose dimycolate (TDM) and its stereoisometric
derivatives, trehalose dicorynomycolates (TDCMs), with low toxicity on lung
metastasis of tumour cells in mice.
AB - We examined the effect of semisynthetic trehalose-6,6 '-dimycolate (TDM) and its
synthetic stereoisomeric derivatives (trehalose 6,6'-dicorynomycolates; TDCMs)
prepared in oil-in-water (o/w) emulsion on inhibition of lung metastasis produced
by highly metastatic murine tumour cells, colon 26-M3.1 carcinoma and B16-BL6
melanoma cells, using experimental and spontaneous metastasis models. Intravenous
(i.v.) administration of TDM (100 microg/mouse) 1, 3 or 8 days before tumour
inoculation significantly inhibited lung metastasis of colon 26-M3.1 cells, in a
dose-dependent manner. Single administration of TDM 1 day after tumour
inoculation also showed the therapeutic effect on experimental lung metastasis of
colon 26-M3.1 cells. Similarly, multiple administrations of TDM after tumour
inoculation resulted in a significant inhibition of spontaneous lung metastasis
of B16-BL6 cells (on day 35), although it showed no effect on suppression of
tumour growth (on day 21). In comparison of toxicity in vivo among TDM and four
TDCMs such as TDCM(2R,3R), TDCM(2S,3R), TDCM(2R,3S) and TDCM(2S,3S), all of the
TDCMs appeared to be less toxic than TDM itself. Furthermore, all of the TDCMs
were prophylactically as well as therapeutically active for inhibition of lung
metastasis of both colon 26-M3.1 and B16-BL6 tumour cells, showing higher
inhibitory activity than that of TDM. In particular, TDCMs induced a marked
suppression of the growth of B16-BL6 tumour cells in vivo. These results suggest
that systemic administration of TDM as well as TDCMs led to inhibition of tumour
metastasis and TDCMs are more potential to suppress tumour growth and inhibit
tumour metastasis than TDM.
PMID- 10195786
TI - Immunization with recombinant Helicobacter pylori urease decreases colonization
levels following experimental infection of rhesus monkeys.
AB - Rhesus monkeys, naturally colonized with H. pylori as indicated by culture and
histology were immunized with either 40 mg recombinant H. pylori urease
administered orally together with 25 microg Escherichia coli heat-labile
enterotoxin (LT) or immunized with LT alone. An initial 6 doses were administered
over an 8 week period. All five vaccinated monkeys had a greater than two-fold
rise in urease-specific serum IgG and IgA level and urease-specific salivary IgA
was induced in 3 of 5 vaccinated animals after 6 or 7 doses of vaccine.
Vaccination had no measurable therapeutic effect on H. pylori colonization. H.
pylori was eradicated from these monkeys with a course of antimicrobials plus
omeprazole, a 7th vaccine dose was given (10 months after the 6th dose) and they
were rechallenged with H. pylori. Necropsy was performed 23 weeks after
rechallenge and H. pylori colonization was determined by histological examination
of 12 individual gastric sites. A significant reduction in colonization (p < or =
0.0001; Friedman's analysis of variance) was found in the vaccinated animals.
Histopathologic examination of necropsy tissues also revealed a trend towards
reduced gastritis and epithelial alterations in the vaccinated group compared to
animals receiving LT alone. This study provides the first evidence for effective
vaccination of nonhuman primates against H. pylori, and preliminary evidence that
a reduction in bacterial density attributable to immunization may lessen gastric
inflammation.
PMID- 10195787
TI - Synthetic peptide antigens induce antibodies to Taenia ovis oncospheres.
AB - Sheep immunised with the Taenia ovis recombinant 45W antigen are protected from
infection with the parasite. Two peptides were synthesised corresponding to
putative host-protective regions at the N- and C-termini of 45W. Sera from sheep
immunised with 45W or related recombinant proteins reacted strongly with the N
terminal peptide. Approximately 40% of the antibody directed against 45WB/X, a
truncated form of 45W, was found to be directed against the N-terminal peptide
sequence. Sheep were immunised with the N- and C-terminal peptides alone or
conjugated to a carrier protein. The N-terminal peptide was found to be highly
immunogenic whereas the C-terminal peptide required conjugation to a carrier
protein to be immunogenic. Antibodies raised against each of these immunogens
crossreacted with the parent protein, 45WB/X, however, only antibodies specific
for the N-terminal peptide were found to bind to antigens from the T. ovis
oncosphere.
PMID- 10195788
TI - Adjuvant effect of cholera toxin on systemic and mucosal immune responses in
chickens infected with E. tenella or given recombinant parasitic antigen per os.
AB - We investigated the adjuvant effect of cholera toxin (CT) on the intestinal and
systemic immune systems of chickens. The CT was given orally, mixed with a non
replicating antigen, a recombinant Eimeria protein, IPEI, or with a replicating
one, Eimeria tenella parasite. There were increases in the specific IgA and IgG
responses to the recombinant protein IPEI, with a significant anti-1PE1 IgG
response in the duodenum (p < 0.05) and caecum (p < 0.05) 4 weeks after
immunization and a specific IgA (p < 0.05) response in the duodenum after 3
weeks. A transient anti-1PE1 IgG (p < 0.05) response was detected in the serum 1
week post-injection and an IgA response (p < 0.05) at 2 weeks. CT given with the
replicative parasite caused no change in the intestinal and systemic immune
responses with 1 or 3 immunizations although a specific antiparasitic in vitro
proliferation of the spleen cells from infected chickens was observed.
Nevertheless, 0.05 mg CT given per os to chickens was strongly immunogenic in
both experiments. A strong serum IgG (p < 0.01) response was detected as soon as
1 week after the end of the immunization protocol with 1PE1 and 2 weeks after
infection with E. tenella. Strong anti-CT IgG responses were also detected by the
second week post-immunization in the duodenum and caeca (p < 0.01). Hence, CT can
be used as a mucosal adjuvant in chickens to improve the intestinal immune
response.
PMID- 10195789
TI - Measles antibody seroprevalence rates among immunized Inuit, Innu and Caucasian
subjects.
AB - Measles antibody seroprevalence was compared in Innu, Inuit, and Caucasian
peoples of northern Newfoundland, Canada, who were immunized with a single dose
of M-M-R-II (Merck Research Laboratories) vaccine. Healthy, volunteer
schoolchildren (n = 606) were enrolled. Measles antibody was measured with a
whole virus measles-specific IgG EIA. Native (Innu and Inuit) schoolchildren (n =
253) had a significantly higher seropositive rate (83%) after a single dose of
measles vaccine compared to Caucasian (n = 353) children (76%; p = 0.025), and
higher mean antibody levels after immunization compared to Caucasian children
(1.74 EIA units, vs. 1.63; p = 0.06). Caucasian children were more likely to have
been immunized after age 15 months (20.6% vs. 9.6%; p = 0.001). There was no
significant difference in the mean time interval between immunization and blood
sampling for natives versus Caucasian (8.0 years vs. 7.95 years; p = 0.49). After
adjustment for time from immunization and age at immunization, there remained a
marginally significant racial difference in seropositivity (OR = 1.65, 95% CI
0.96, 2.83, p = 0.068). The unadjusted odds ratio for seropositivity (comparing
natives vs. non-natives, combining negative and equivocal results) was 1.66 (95%
CI 1.06-2.59, p = 0.018). The higher measles-seropositive rate found among native
compared to non-native Canadian children suggests that genetic and/or
environmental factor(s) affect circulating antibody levels following
immunization. The determination of these sources of variability may lead to the
development of more efficacious vaccines or delivery strategies.
PMID- 10195790
TI - Protection against tick-borne encephalitis virus isolated in Japan by active and
passive immunization.
AB - In order to establish a firm preventive measure for tick-borne encephalitis (TBE)
in Japan, we evaluated the immune response of European vaccine against Japanese
TBE virus strain (Oshima 5-10) for man and mouse. Furthermore, the efficacy of
pre- and post-exposure protection by a polyclonal rabbit anti-TBE virus serum was
examined in the mouse model. 80% of vaccinees seroconverted against Oshima 5-10
strain after the 2nd immunization of vaccine and the remaining 20% seroconverted
after the 3rd immunization. Two persons with pre-existing anti-Japanese
encephalitis virus (JEV) antibodies showed low immune responses against TBE
virus. In mouse vaccination and challenge tests, efficient protection was
observed in mice challenged with lethal doses of Oshima 5-10 strain as well as
those observed in mice with the Western subtype and the Far Eastern subtype of
TBE strains. Pre-exposure treatment with rabbit anti-TBE virus serum provided
complete protection against lethal challenge with Oshima 5-10 strain. For post
exposure treatment with the antibody, significant protection was observed when
mice were treated 24 h after virus challenge, whereas it was not observed 48 h
after virus challenge. reserved.
PMID- 10195791
TI - Immunogenicity of synthetic HIV-1 V3 loop peptides by MPL adjuvanted pH-sensitive
liposomes.
AB - A successful HIV-1 vaccine should be capable of generating humoral and cellular
immune responses at the same time. The only response shown to be effective in
this regard is virus-neutralization antibodies and virus-specific cytotoxic T
lymphocytes (CTL) directed against the viral antigens. In the present study, it
is shown that V3 peptides encapsulated pH-sensitive liposomes elicit the virus
neutralization antibodies and virus specific CTL response at the same time in
Balb/c mice. None of the immunization protocols elicited an antibody response and
CTL response when R15K and T26K was used as immunogen without liposomes. In
contrast, antibodies and CTL response were detectable in the mice which were
immunized with peptide encapsulated pH-sensitive liposomes. Antibody production
was confirmed by virus neutralizing assay. CD4+ T-cells are involved in target
cell lysis to some degree but CTL activity is mainly due to the CD8 + T-cells.
The consistency of the antibody and CTL response was related to the V3 loop
peptides size. The T26K (26mer) peptide induced a stronger antibody and CTL
response than R15K (15mer) in vivo. Based on the results of this study, T26K was
used as a potentially effective HIV-1 vaccine component and T26K encapsulated pH
sensitive liposomes composed of phosphatidylethanolamine-beta-oleoyl-gamma
palmitoyl (POPE)/cholesterol hemisuccinate (CHOH)/monophosphoryl lipid A (MPL)
(7:3:0.1, mole ratio) may be used as a potentially immunomodulating adjuvant
system for the development of HIV and other viral vaccines.
PMID- 10195792
TI - Is there an advantage to including the nucleoprotein in a rabies glycoprotein
subunit vaccine?
AB - The PV rabies (genotype 1) G and N proteins were produced by recombinant
baculoviruses in insect cells. We tested the ability of recombinant antigens to
synergistically induce an immune response and, particularly, to broaden the
spectrum of Lyssavirus-neutralizing antibodies produced. Cell-free preparations
of recombinant proteins caused an immune response. Recombinant rabies G protein
(RRG) from infected cell extract or supernatant induced virus neutralizing
antibodies (VNAb) against rabies (CVS virus (genotype 1) and in a less extent
against European Bat Lyssavirus-1 (EBL-1:genotype 5) Recombinant rabies N protein
(RRN) induced antibodies that reacted with the rabies virus ribonucleoprotein
(RNP) and primed mice for both the production of VNAb induced by inactivated and
purified rabies virus and the protection conferred by RNP. RRN also had an
adjuvant effect on VNAb production induced by RRG when the two recombinant
proteins were physically associated either encapsulated in liposomes or subjected
to ultrasound treatment. However, there was no increase in production of VNAb
directed against EBL-1 although classical vaccines (genotype 1) induce partial
protection against this virus. thus, beside its adjuvant effect there is some
doubt as to whether including rabies N protein in a rabies subunit vaccine
containing the recombinant G protein would be advantageous.
PMID- 10195793
TI - Intramuscular injection of plasmid DNA encoding cottontail rabbit papillomavirus
E1, E2, E6 and E7 induces T cell-mediated but not humoral immune responses in
rabbits.
AB - To test the efficacy of genetic vaccination against papillomavirus infection,
plasmid DNA encoding cottontail rabbit papillomavirus (CRPV) E1, E2, E6, E7 or
without insert were intramuscularly injected into five groups of rabbits.
Peripheral blood mononuclear cells (PBMCs) showed specific proliferation upon in
vitro stimulation with E1, E2, E6 or E7 proteins in a majority of vaccinated
rabbits but Western blot analysis did not detect antibodies specific for these
viral proteins in rabbit serum. All rabbits grew papillomas after virus challenge
and none of the rabbits showed systemic papilloma regression. These observations
showed that intramuscular injection of plasmid DNA encoding CRPV E1, E2, E6 or E7
induced CD4+ T cell-mediated but not humoral immune responses, and did not result
in the protection of rabbits from virus infection.
PMID- 10195794
TI - A novel vaccine regimen utilizing DNA, vaccinia virus and protein immunizations
for HIV-1 envelope presentation.
AB - Recombinant DNA and vaccinia virus (VV) vectors that express envelope (Env)
proteins of the human immunodeficiency virus (HIV) have each been prominently
utilized in vaccine development. These two vectors (termed DNA-Env and VV-Env)
are attractive vaccine candidates due to their abilities to elicit both cytotoxic
T-lymphocyte and B-cell responses. Our previous work demonstrated that DNA-Env
primed animals, that were relatively unresponsive to DNA-Env boosters, could be
immunized with VV-Env to yield more than a 100-fold increase in antibody
responses. Here we show: (1) results with an optimized vaccine regimen that
primes with DNA-Env, boosts with VV-Env, and re-boosts with purified Env
proteins, (2) enhanced responses with 8 rather than 16 week intervals between VV
Env and protein immunizations, and (3) the failure of single Env vaccines to
reproducibly elicit responses toward heterologous Env, regardless of the
vaccination regimen utilized. Results encourage the use of poly-Env vaccine
cocktails administered via DNA/VV/protein regimens in future non-human primate
and clinical studies.
PMID- 10195795
TI - Effects of different adjuvants on rotavirus antibody responses and protection in
mice following intramuscular immunization with inactivated rotavirus.
AB - I.m. immunization of mice with inactivated rotavirus particles protects against
subsequent infection. To optimize protection, the effects of different adjuvants
(QS-21, QS-7, QUIL A, PCPP and RAS) with potential for human use were compared.
Twenty-eight days after i.m. immunization with 20 microg of purified, UV/psoralen
inactivated murine rotavirus (EDIM), either with or without adjuvant, BALB/c mice
were orally challenged with live EDIM and virus shedding was measured. All five
adjuvants stimulated large (P < 0.001) increases in rotavirus antibody, but
significant differences were found between adjuvants. The order of rotavirus IgG
responses, i.e. no adjuvant < RAS < QS-7 < Quil A < QS-21 < PCPP, was the same as
the order of protection except that QS-21 and PCPP were reversed. These results
establish the importance of adjuvants during i.m. immunization with rotavirus and
identify those with the greatest potential.
PMID- 10195796
TI - Self-assessment of puberty: problems and potential.
PMID- 10195797
TI - The Parma High School epidemiological survey: eating disorders.
PMID- 10195798
TI - Piercing and tattooing in patients with congenital heart disease: patient and
physician perspectives.
AB - PURPOSE: The frequency and safety of ear piercing and tattooing were assessed in
a group of children, adolescents, and adults with congenital heart disease (CHD).
Also, a group of physicians who care for adolescents and adults with CHD were
surveyed for opinions and experiences regarding piercing and tattooing. METHODS:
An eight-question survey was mailed to 445 patients (181 adults and 264 children)
from one center. A different five-question survey was mailed to 176 physician
members of the International Society of Adult Congenital Cardiac Disease.
RESULTS: The patient survey was completed by 152 of 445 (34%) patients (mean age
+/- standard deviation 19.8 +/- 16.2 years; range 0.25-67 years). Eighty-eight of
152 (58%) patients were female. Ear piercing occurred in 65 of 152 (43%) patients
(mean age 12.4 +/- 8.7 years; range 0.25-45 years). Prior to piercing, only 4 of
65 (6%) patients took antibiotics, but 15 of 65 (23%) had piercing-related
infections. No patient had endocarditis. Infections occurred 1 week to 3 years
after piercing. All were local skin infections. Tattoos were placed in 8 of 152
(5%) patients (median age 17.5 years; range 13-56 years). No antibiotic use or
infections were reported in patients with tattoos. The physician survey was
completed by 118 of 176 (67%) physicians. The majority of physicians did not
approve of patients having piercing or tattooing performed. However, 60% of
physicians believed that antibiotic prophylaxis is indicated for these
procedures. CONCLUSIONS: Despite the opinion of many physicians, most patients do
not take antibiotic prophylaxis for piercing and tattooing. Patients apparently
do not suffer serious sequelae. The efficacy of standard antibiotic regimes as
applied to ear piercing and tattooing requires further study, since these
procedures are increasingly popular in modern society.
PMID- 10195799
TI - Self-reported abuse history and adolescent problem behaviors. I. Antisocial and
suicidal behaviors.
AB - PURPOSE: To examine the associations of self-reported abuse and sexual
molestation with self-reported antisocial behavior and suicidal ideation/behavior
in a general population of adolescents. METHODS: We used a stratified cluster
sampling procedure with replacement to sample 4790 students in Washington State
public schools in Grades 8, 10, and 12. Students were asked in a self
administered questionnaire whether they had ever been abused by an adult and
whether they had ever been sexually molested. They were also asked about
antisocial behavior and suicidal ideation and behavior in the past year. We
conducted polytomous logistic regressions, controlling for gender and grade,
using Software for the Statistical Analysis of Correlated Data (SUDAAN). RESULTS:
Reported abuse history was associated with antisocial behavior and with suicidal
ideation and behavior. The associations were stronger for abuse and molestation
than for nonsexual abuse or molestation alone, and stronger at higher levels of
severity (e.g., suicide attempts vs. suicidal thoughts). For example, adjusted
odds ratios and 95% confidence intervals (in parentheses) for abuse and
molestation were 4.4 (3.1-6.2) for suicidal thoughts, 6.8 (4.4-10.4) for suicide
plan, 12.0 (7.9-18.4) for noninjurious suicide attempt, and 47.1 (23.3-95.3) for
injurious suicide attempt. For abuse alone, these figures were 2.3 (1.7-3.2), 3.1
(2.1-4.6), 5.1 (3.3-7.8), and 11.8 (4.4-31.9), respectively. CONCLUSIONS: Efforts
to reduce antisocial behavior and suicidal ideation/behavior in adolescence,
particularly early or severe manifestations of the behaviors, should consider the
possible role of a history of maltreatment, especially the possibility of sexual
abuse.
PMID- 10195800
TI - Self-reported abuse history and adolescent problem behaviors. II. Alcohol and
drug use.
AB - PURPOSE: We examined the associations of self-reported abuse and sexual
molestation with self-reported alcohol and drug use in a general population of
adolescents. METHODS: We used a stratified cluster sampling procedure with
replacement to sample 4790 students in Washington State public schools in Grades
8, 10, and 12. Students were asked whether they had ever been abused by an adult
and whether they had ever been sexually molested. They were also asked about
their levels of alcohol and drug use and about early initiation of substance use.
We conducted polytomous logistic regressions, controlling for gender and grade,
using Software for the Statistical Analysis of Correlated Data (SUDAAN). RESULTS:
We identified associations between reported abuse history and alcohol and drug
use in adolescence and early initiation of substance use. The associations
between reported abuse history and alcohol use were stronger at younger ages. The
strongest association was between combined abuse and molestation, and relatively
severe (heavy) drinking by eighth graders (odds ratio, 7.9; 95% confidence
interval, 2.6-17.4). For drug use, the associations with reported abuse history
were slightly stronger at higher levels of severity and for combined abuse and
molestation compared to nonsexual abuse. For early initiation, the associations
with abuse history were stronger for combined abuse and molestation than for
nonsexual abuse or molestation alone, and stronger for marijuana use/regular
drinking than for alcohol/cigarette experimentation. For example, adjusted odds
ratios and 95% confidence intervals (in parentheses) for combined abuse and
molestation were 3.5 (2.8-4.5) for alcohol/cigarette experimentation and 12.2
(6.3-23.6) for marijuana use/regular drinking by age 10. For abuse alone, these
figures were 2.5 (2.0-3.1) and 4.7 (3.0-7.3), respectively. CONCLUSION: Efforts
to reduce substance use and abuse in adolescence, particularly heavy use and use
early in adolescence, should consider the possible role of a history of
maltreatment.
PMID- 10195801
TI - Communication about sexual issues: mothers, fathers, and friends.
AB - PURPOSE: To identify the content, characteristics, and comfort level of
discussions about sexuality held between mothers and their early adolescent
children and to determine the extent to which the conversations predicted sexual
values and initiation of sexual intercourse of the adolescent. METHODS: This was
part of a larger study to evaluate the impact of personal family characteristics
on human immunodeficiency virus risk-reduction behavior among low-income
predominately African-American adolescents, ages 13-15 years. Adolescents
attending a metropolitan community-based afterschool program and their mothers
were invited to participate in a 1-hour interview. Mothers and adolescents were
interviewed separately. The interview included questions about the type of
information related to sexuality that adolescents discussed with mothers,
fathers, and friends; in addition, mothers were asked what topics they discussed
with their adolescents. Four hundred five adolescents and 382 mothers
participated. Some mothers had more than one adolescent in the study. RESULTS:
The results showed that both male and female adolescents were more likely to
discuss sexual topics with their mothers than their fathers. Male adolescents
were more likely than female adolescents to discuss sex-based topics with their
fathers. Both male and female adolescents were less likely to discuss sex-based
topics with their friends than with their mothers, but more likely to discuss
these topics with their friends than their fathers. Content of conversations of
male adolescents was fairly consistent among mothers, fathers, and friends, and
sexually transmitted disease/acquired immune deficiency syndrome and condom use
were popular topics of discussion. Female adolescents tended to talk about the
menstrual cycle with their mothers, sexual abstinence with their fathers, and
sexual intercourse with their friends. Adolescents who reported a greater number
of topics discussed with their mothers were more likely not to have initiated
sexual intercourse and to have conservative values, whereas adolescents who
reported a greater number of topics discussed with their friends were more likely
to report the initiation of intercourse and more "liberal" sexual values. Both
male and female adolescents were most comfortable discussing sexual issues with
their friends. Male adolescents were less comfortable talking to mothers, but
more comfortable talking to their fathers than were females. Mothers were likely
to report feeling very comfortable talking about almost all discussion areas.
Fathers' comfort level was not measured, as they were not directly questioned.
CONCLUSION: Early adolescence (13-15 years old) is characterized by more sex
based discussions with mothers than friends or fathers. Daughters and sons
discuss different topics with their fathers, although discussion by both genders
with fathers is limited. If an adolescent talks more with the mother about sexual
issues than with friends, he/she is less likely to initiate sexual intercourse
and more likely to have conservative values. This points to the importance of
fostering good communication and comfort between parents and adolescents about
sexual issues.
PMID- 10195802
TI - Service utilization among homeless and runaway youth in Los Angeles, California:
rates and reasons.
AB - PURPOSE: To describe the service utilization patterns of homeless and runaway
youth in a "service-rich" area (Los Angeles, California); identify demographic
and other correlates of utilization; and contextualize the findings with
qualitative data. METHOD: During Phase 1 of this study, survey data were
collected from an ethnically diverse sample of 296 youth aged 13-23 years,
recruited from both service and natural "hang-out" sites using systematic
sampling methods. During Phase 2, qualitative data were collected from 46 youth
of varying ethnicities and lengths of time homeless. RESULTS: Drop-in centers and
shelters were the most commonly used services (reported by 78% and 40%,
respectively). Other services were used less frequently [e.g., medical services
(28%) and substance abuse treatment (10%) and mental health services (9%)].
Utilization rates differed by ethnicity, length of time in Los Angeles, and city
of first homeless episode (Los Angeles vs. all others). Shelter use was strongly
associated with use of all other services. Despite youths' generally positive
reactions to services, barriers were described including restrictive rules,
confidentiality and reporting problems, and negative interactions with staff
members. Youth suggested improvements including more targeted services, more long
term services, revised age restrictions, and more and/or better job training and
transitional services to get them off the streets. CONCLUSIONS: Because shelters
and drop-in centers act as gateways to other services and offer intervention
potential for these hard-to-reach youth, it is vital that barriers to use of
these services are eliminated.
PMID- 10195803
TI - Validity of self-assessment of pubertal maturation in African American and
European American adolescents.
AB - PURPOSE: To evaluate interobserver reliability of physician assessments of
pubertal maturation and to evaluate the validity of self-assessment compared to
physician assessments of pubertal maturation by girls in a multiethnic sample.
METHODS: The study design is descriptive. A total of 107 8-17-year-old healthy
volunteers from settings with large minority populations in the Houston
metropolitan area were recruited for a study on adolescents' energy needs. The
two outcome measures were interobserver reliability between two physicians'
assessments of breast and pubic hair, and the self-assessment of breast and pubic
hair maturation compared to physicians' assessments. RESULTS: The kappa
coefficient for physician interobserver agreement for breast maturation was 0.5.
The kappa coefficient for physician interobserver agreement for assessment of
pubic hair was 0.79. The kappa coefficient for the validity of self-assessment of
breast development was 0.34, and that for self-assessment of pubic hair was 0.37.
CONCLUSION: Interobserver agreement for physician assessment of breast maturation
was low and self-assessment of breast maturation was not reliable in this group
of adolescent girls. However, whereas physician interobserver agreement for pubic
hair was good, self-assessment of pubic hair maturation was not reliable in this
group of adolescent girls.
PMID- 10195804
TI - Self-assessment of sexual maturation in adolescent females with anorexia nervosa.
AB - PURPOSE: To evaluate the accuracy of self-assessment of pubertal maturation and
to determine the desired stage of pubertal maturity in adolescent females with
anorexia nervosa. METHODS: Standardized figure drawings depicting Tanner's sexual
maturation stages were given to a consecutive sample of 40 adolescent females
with anorexia nervosa who were instructed to assess current and desired pubertal
development. Pubertal development was assessed independently by two
investigators. The percent agreement between physician and subject ratings was
determined. RESULTS: Percent agreement between physician and subject ratings was
30% for developmental stage for breasts and 50% for pubic hair. Subjects
underestimated breast development 3.4 times as often as they overestimated it and
overestimated pubic hair development 1.5 times as often as they underestimated
it. Multivariate probit analysis showed that inaccuracy in breast self-assessment
was inversely related to a desire for sexual maturity (p < 0.05). Ninety percent
of subjects stated that their desired stage of breast development was equal to or
more mature than their present stage. Eighty percent stated that their desired
stage of pubic hair development was equal to or more mature than their present
stage. CONCLUSIONS: Self-assessment of sexual maturity by adolescents with
anorexia nervosa using standardized figure drawings depicting Tanner's stages is
not accurate. Patients desiring a sexually immature body were most likely to be
inaccurate in their self-assessment of their pubertal stage.
PMID- 10195805
TI - Prevalence of eating disorders in a Spanish school-age population.
AB - PURPOSE: To determine the prevalence of eating disorders (anorexia nervosa,
bulimia, and partial syndromes) in students in a Madrid school district during
the 1993-1994 academic period. The results were compared with those of an earlier
study performed in 1985-1986 and with findings in other countries. METHODS: In
the first phase, 1314 adolescents (731 girls and 583 boys) with a mean age of
15.05 +/- 0.98 years were surveyed according to the Eating Disorder Inventory
(EDI) and a psychosocial data survey. Of these, 1281 (97.48%) [724 girls (99.04%)
and 557 boys (95.54%)] were considered appropriate for the study. The risk
population included individuals with a total EDI score over 50, plus a drive for
thinness (DT) score over 10; 180 girls (24.86%) and 19 boys (3.41%) were
identified on this basis. To reduce possible false negatives, those whose score
on the bulimia scale was over 5, with amenorrhea of more than 3 months duration
and a body mass index (weight in kilograms per height in square meters) under 18
were also considered to be at risk. The total risk population thus defined
consisted of 293 adolescents (22.87%): 67 boys (12.02%) and 226 girls (31.21%).
In the second phase, all risk subjects were reevaluated with a semistructured
interview for ED, and they were also weighed and measured. In all, 156
adolescents (53.24%)[103 girls (45.57%) and 53 boys (79.10%)] participated in
person. The remaining 137 subjects completed the interview by telephone.
Diagnostic and Statistical Manual (DSM)-III-R diagnostic criteria were applied.
RESULTS: Five girls (0.69% of the total study population) fulfilled the DSM-III-R
criteria for anorexia nervosa, and nine (1.24%), for bulimia nervosa. Two boys
(0.36%) had bulimia. Twenty girls (2.76%) and three boys (0.54%) represented
partial syndromes. The results of adding the full and partial syndromes showed
that 4.7% of the girls and 0.9% of the boys had eating disorders. CONCLUSIONS:
This study demonstrates an increase in the prevalence of eating disorders in
Madrid, reaching similar levels to those reported in the literature for other
developed countries.
PMID- 10195806
TI - Reproductive health risk behavior survey of Colombian high school students.
AB - PURPOSE: To establish rates of potentially risky sexual behaviors among Colombian
adolescent students. METHODS: A total of 230 9th and 11th graders at a Colombian
high school (69% of enrolled students) were anonymously surveyed about selected
reproductive health behaviors using the Centers for Disease Control and
Prevention's self-administered Youth Risk Behavior Survey. RESULTS: The response
rate was >90%. The group was demographically representative of students. Twenty
nine percent of the group had engaged in intercourse (13% of 9th and 43% of 11th
graders). Male gender [beta = 0.7873; odds ratio (OR) = 2.09; 95% confidence
interval (CI) = 1.57-3.08] and increasing age (beta = 0.3413; OR = 1.41; 95% CI =
1.02-1.93) were each significantly correlated with prior sexual activity.
Compared with females, males initiated intercourse at a significantly earlier age
(beta = 0.284; p < .001) but did not report significantly more partners (means
2.1 vs. 1.4; chi2 = 1.25; p = .262). Forty-eight percent of respondents used
contraception during their last encounter. Sixty-three percent used oral
contraceptives or condoms, while the remainder used less effective methods.
Contraceptive use did not correlate with gender or age. Age was significantly and
positively correlated with use of alcohol prior to sexual activity (B = 1.28; OR
= 3.6; 95% CI = 1.49-8.44). CONCLUSIONS: Compared with U.S. populations of
similar ages, the Colombian group surveyed had fewer sexually active members,
reported fewer partners, and used contraception with lower frequency.
PMID- 10195807
TI - Imperforate hymen and ruptured hematosalpinx: a case report with a review of the
literature.
AB - The imperforate hymen is a common genital disorder, but a ruptured hematosalpinx
is a fairly rare complication. This article presents one case with an imperforate
hymen as well as a bilateral hematosalpinx, with unilateral ruptured
hematosalpinx, giving a picture of acute abdomen. The pathology, diagnosis,
treatment, and complications of these rare cases are discussed. The most
important factor for the clinician to remember is the history; a simple
inspection provides the diagnostic clue.
PMID- 10195808
TI - Decreased ethanol sensitivity and tolerance development in gamma-protein kinase C
null mutant mice is dependent on genetic background.
AB - Initial sensitivity and tolerance development to the sedative-hypnotic and
hypothermic effects of ethanol were investigated in gamma-protein kinase C (PKC)
null mutant mice. Null mutants from a C57BL/6J x 129/SvJ mixed genetic background
demonstrated decreased ethanol sensitivity and failed to develop chronic
tolerance after 10 days of ethanol liquid diet. However, when the null mutation
was introgressed onto a C57BL/6J background for six generations, the "no
tolerance" phenotype for sedative-hypnotic and hypothermic effects of ethanol was
no longer apparent Outcrossing the gamma-PKC null mutation to a C57BL/6J x
129/SvEvTac mixed background restored the "no tolerance" phenotype to ethanol
induced sedation after chronic ethanol diet; however, as measured by hypothermia,
tolerance was still evident in the null mutant mice. These observations and the
results of tests of chronic tolerance in the C57BL/6J, 129/SvJ, and 129/SvEvTac
background inbred strains indicate that gamma-PKC plays an important role in
initial sensitivity and tolerance to ethanol. However, the impact of gamma-PKC is
modulated by the background genotype. These results stress the importance of
including the effect of genetic background when evaluating the effects of single
gene mutations on quantitative behavioral traits.
PMID- 10195809
TI - Independent ethanol- and sucrose-maintained responding on a multiple schedule of
reinforcement.
AB - Assessment of drug effects on two different reinforcers at the same time requires
that each reinforcer be sampled at approximately the same time. One procedure
that effectively produces this result is the use of a multiple schedule of
reinforcement in which two different reinforcers are presented in alternating 2
min components. In our study, sucrose and ethanol solutions were made available
after appropriate lever-press responding. Subjects were trained to self
administer 10% ethanol using a sucrose-substitution procedure and to discriminate
light cues associated with the different reinforcers until stable reinforcer
directed responding was achieved on both the ethanol- and the sucrose-associated
lever during the changing 2-min components of the schedule. Subsequently, the
reinforcer solution presented on one lever was held constant while the
concentration of the alternate reinforcer was manipulated, i.e., ethanol
concentrations of 0 to 15% and sucrose concentrations of 0 to 10% were assessed.
This multiple schedule procedure resulted in sustained and independent ethanol-
and sucrose-reinforced behavior. Manipulation of the characteristics of one
reinforcer had no effect on behavior maintained by the alternate reinforcer.
Increases in sucrose concentration resulted in increases in sucrose-directed
responding with no change in ethanol responding, and increases in ethanol
concentration resulted in increases in ethanol intake with no change in sucrose
responding. Our methods can be used to examine differential drug effects on
ethanol- and sucrose-reinforced behavior in the same animal over a single time
course without the confounds or interference from the concurrently available
reinforcer.
PMID- 10195811
TI - Increased expression of mitochondrial genes in human alcoholic brain revealed by
differential display.
AB - Polymerase chain reaction (PCR)-based differential display was used to screen for
alterations in gene expression in the mesolimbic system of the human alcoholic
brain. Total RNA was extracted from the nucleus accumbens of five alcoholic and
five control brains. A selected subpopulation of mRNA was reverse-transcribed to
cDNA and amplified by PCR. A differentially expressed cDNA fragment was
recovered, cloned, and sequenced. Full sequence analysis of this 467 bp fragment
revealed 98.2% homology with the human mitochondrial 12S rRNA gene. Dot-blot
analysis showed increased expression of this gene in nucleus accumbens and
hippocampus, but not in the superior frontal cortex, primary motor cortex,
caudate, and pallidus/putamen in a total of eight human alcoholic brains,
compared with seven control brains. A similar increased expression was observed
by dot-blot analysis, using RNA from the cerebral cortex of rats chronically
treated with alcohol vapor. Hybridization of a 16S rRNA oligonucleotide probe
indicated that the expression of both rRNAs genes was significantly increased in
nucleus accumbens. These results indicate that chronic alcohol consumption
induces alteration in expression of mitochondrial genes in selected brain
regions. The altered gene expression may reflect mitochondrial dysfunction in the
alcohol-affected brain.
PMID- 10195810
TI - Effect of chronic ethanol consumption on fatty acid profile of heart tissue in
rats.
AB - The effect of chronic ethanol ingestion on fatty acid composition and lipid
content of heart tissue in rats, and whether this effect depends on age, was
studied. Rats were maintained on a 30% ethanol solution in drinking water for 3
and 5 months. Control animals were given water. Phospholipid concentration was
unchanged in the ethanol-fed groups, compared with control groups, whereas total
cholesterol content was increased at 5 months of treatment. An increase in
stearic acid, palmitoleic acid, and 22:5n6 were observed at 3 months of ethanol
ingestion. When ethanol was administered for 5 months, polyunsaturated fatty
acids series n3 were decreased with respect to control. The effect of age on the
profile of fatty acids of heart showed an increase of monounsaturated fatty acids
and a decrease of long-chain polyunsaturated fatty acids in both control and
ethanol-fed rats. The effect of ethanol ingestion on fatty acid composition of
heart tissue is not very pronounced, but the small changes observed could
contribute to the development of functional and electrophysiological features of
alcoholic heart disease.
PMID- 10195812
TI - Gender differences in blood levels, but not brain levels, of ethanol in rats.
AB - Female rodents tend to drink more alcohol than males, a difference that emerges
at puberty and appears to vary over the female estrous cycle. In addition, male
and female rodents display different responses to alcohol; for example, female
rats are reported to have faster elimination rates than males. We were interested
in whether circulating ovarian hormones influence alcohol distribution to or
elimination from the brain of rats, which might explain observed differences in
drinking behavior. We administered 0.8 g/kg of ethanol via intraperitoneal
injection to age-matched male and female Sprague-Dawley rats. Extracellular brain
ethanol was sampled using microdialysis, and vascular ethanol concentrations were
determined via tail blood collection, in two separate experiments. Ethanol
pharmacokinetic parameters were calculated for both compartments. There were no
differences in pharmacokinetic parameters due to gender or estrous cycle stage in
brain ethanol concentration profiles. There were, however, differences in blood
ethanol profiles: females showed faster elimination rates and a smaller area
under the ethanol concentration versus time curve than males. In addition, the
maximum concentration varied significantly across the estrous cycle. These
results suggest that (1) circulating ovarian hormones do not influence alcohol
distribution to the brain, but do influence distribution to more peripheral
tissues such as the tail; and (2) apparent differences in tail blood alcohol
levels may not reflect differences in brain levels.
PMID- 10195813
TI - Effects of microinjection of the D2 dopamine antagonist raclopride into the
ventral tegmental area on ethanol and sucrose self-administration.
AB - From previous microinjection studies, a reciprocal feedback between the nucleus
accumbens and the ventral tegmental area (VTA) has been implicated in the
reinforcing stimulus actions of ethanol and sucrose. In these studies, the
effects of self administration of ethanol or sucrose solutions on maintained
responding were similar when a dopamine antagonist was injected in the nucleus
accumbens or a dopamine agonist was injected into the VTA. Our study was
performed to determine if the effects on responding that had been observed when a
dopamine agonist was injected into the nucleus accumbens would occur after an
injection of a dopamine antagonist into the VTA. Male, Long-Evans rats were
initially trained to lever press using either 10% ethanol or 75% sucrose
solutions as the reinforcers. Bilateral guide cannulae were implanted to allow
microinjection into the VTA of differing doses of the dopamine D2 antagonist,
raclopride. Only at the highest dose tested (10 microg) was any effect observed
on responding maintained by either reinforcer. The effect was minimal and
different from that observed after the microinjection of a dopamine agonist into
the nucleus accumbens. This suggests that either the actions of the nucleus
accumbens agonist manipulation involved other processes or that the level of
enhanced dopamine release in the nucleus accumbens from the VTA antagonist
injection was not sufficient to mimic the effect of the nucleus accumbens agonist
injections.
PMID- 10195814
TI - Association analysis of sequence variants of GABA(A) alpha6, beta2, and gamma2
gene cluster and alcohol dependence.
AB - Quantitative trait analyses in mice suggest a vulnerability locus for
physiological alcohol withdrawal severity on a chromosomal segment that harbors
the genes encoding the alpha1, alpha6, beta2, and gamma2 subunits of the gamma
aminobutyric acid type-A receptor (GABR). We tested whether genetic variation at
the human GABA(A) alpha6, beta2, and gamma2 gene cluster on chromosome 5q33
confers vulnerability to alcohol dependence. The genotypes of three nucleotide
substitution polymorphisms of the GABRA6, GABRB2, and GABRG2 genes were assessed
in 349 German alcohol-dependent subjects and in 182 ethnically matched controls.
To eliminate some of the genetic variance, three more homogeneous subgroups of
alcoholics were formed by: (1) a history of alcohol withdrawal seizure or
delirium (n = 106); (2) a history of parental alcoholism (n = 120); and (3) a
comorbidity of dissocial personality disorder (n = 57). We found no evidence that
any of the investigated allelic variants confers vulnerability to either alcohol
dependence or severe physiological alcohol withdrawal symptoms or familial
alcoholism (p > 0.05). The frequency of the T allele of the GABRA6 polymorphism
was significantly increased in dissocial alcoholics [f(T) = 0.799] compared with
the controls [f(T) = 0.658; p = 0.002; OR(T+) = 7.26]. Taking into account the
high a priori risk of false-positive association findings due to multiple
testing, further replication studies are necessary to examine the tentative
phenotype-genotype relationship of GABRA6 gene variants and dissocial alcoholism.
PMID- 10195815
TI - Effects of dexmedetomidine on rat locus coeruleus and ethanol withdrawal symptoms
during intermittent ethanol exposure.
AB - In the present study, the neuroprotective effects of dexmedetomidine on rat locus
coeruleus were studied during a 5-week intermittent ethanol exposure. Male Wistar
rats (3 to 4 months old) were given ethanol or isocaloric sucrose by intragastric
intubations three times a day for 4 days, which was followed by a 3-day
withdrawal period. This 7-day cycle of ethanol exposure and withdrawal was
repeated five times. Dexmedetomidine (at a dose decreasing from 30 microg/kg to
10 microg/kg, s.c.) was given to the treatment group during the withdrawal phase.
The results showed that, during the 5-week experiment, dexmedetomidine
significantly relieved the ethanol withdrawal syndrome, measured as the sum of
the three most specific symptoms (rigidity, tremor, and irritability). The total
neuron number of locus coeruleus (LC) decreased in the ethanol-treated group by
24%, compared with the nontreated control group and by 11%, compared with the
sucrose-treated control group. Interestingly, the LC neuron numbers were found to
decrease in the sucrose-intubated rats as well, compared with the nontreated
control group. Dexmedetomidine was found to relieve ethanol-induced neuronal loss
in the LC. Dexmedetomidine might be a new interesting alternative in the
treatment of ethanol withdrawal syndrome, particularly due to its possible
neuroprotective effects in the central nervous system.
PMID- 10195816
TI - Ethanol-nicotine interactions at alpha-bungarotoxin-insensitive nicotinic
acetylcholine receptors in rat cortical neurons.
AB - Numerous studies have indicated a correlation between ethanol intake and
cigarette smoking in heavy drinkers. We have studied the underlying
pharmacological basis of this relationship using cultured rat cortical neurons.
These neurons express nicotinic receptors having characteristics similar to those
described for the alpha4beta2 subunit combination. In the presence of alpha
bungarotoxin both acetylcholine (ACh) and nicotine evoked currents with
respective EC50 values of 4.3 and 3.4 microM. The maximal nicotine-activated
response, however, was only 56% that of the maximal ACh current. It was
previously shown that 10 to 100 mM of ethanol potentiated ACh-mediated currents
in these neurons. We demonstrate that 100 mM ethanol similarly potentiates
currents evoked by 300 nM (40%) and 1 microM nicotine 61%). This suggests that an
ethanol-induced potentiation of nicotinic currents may enhance the acute positive
reinforcement associated with nicotine and could increase tobacco use during
heavy ethanol intake. However, further experimentation indicated that the
continuous perfusion of 30, 100, or 300 nM nicotine desensitizes ACh-evoked
currents by 38, 54, and 62%, respectively, with little direct receptor-channel
activation. The residual ACh currents of nicotine-desensitized receptor channels
were potentiated by 100 mM ethanol to nearly the extent as were the
undesensitized control responses. We propose that the opposing effect of ethanol
on nicotine-induced desensitization could also explain the increased tobacco use
observed with excessive drinking. Thus, ethanol has a dual effect regarding
nicotine. It enhances acute nicotine-mediated receptor activation, although
opposing the net effect of nicotine-induced receptor channel desensitization.
PMID- 10195817
TI - Effects of alcohol on immediate-early gene expression in primary cultures of rat
cortical astrocytes.
AB - Ethanol is a potent inhibitor of muscarinic receptor-mediated proliferation in
glial cells. Glial proliferation has been suggested as a major target of ethanol
neurotoxicity during development, leading to the microencephaly that is a
predominant feature of fetal alcohol syndrome. As part of an attempt to
understand the mechanism of ethanol's inhibitory effects on muscarinic receptor
mediated proliferation, this study investigated the effects of ethanol on the
expression of the immediate-early genes (IEGs), c-fos and c-myc, whose induction
is thought to be an essential first step in the initiation of the mitogenic
program. Unexpectedly, ethanol had no inhibitory effect on c-fos and c-myc mRNA
expression induced in primary rat cortical astrocytes by the mitogens carbachol,
histamine, or tetradecanoyl phorbol 13-acetate; rather, a modest potentiation of
IEG expression was observed in the presence of 25 to 100 mM ethanol. Control
experiments showed that ethanol alone was capable of IEG mRNA induction, with 100
mM ethanol inducing IEG mRNA levels comparable with those induced by 100 ng/ml of
tetradecanoyl phorbol 13-acetate; as measured by [3H]thymidine incorporation,
however, 25 to 100 mM ethanol had no effect on proliferation. Experiments with
the protein kinase C inhibitor bisindolylmaleimide and the Ca2+ chelators BAPTA
and EGTA indicated that this IEG induction by ethanol was not mediated by protein
kinase C or Ca2+. A possible explanation for this ethanol-induced IEG expression
in the absence of a proliferative effect might be found in the increasing number
of studies showing IEG involvement (especially that of c-myc) in apoptosis.
PMID- 10195818
TI - Naltrexone effects on ethanol reward and discrimination in C57BL/6 mice.
AB - The effects of the opioid antagonist, naltrexone, on operant responding for oral
ethanol reward delivered on a fixed-ratio schedule, and on the discriminative
stimulus properties of intraperitoneally injected ethanol, was examined in two
separate experiments. The ages, food/water motivational conditions, and
naltrexone doses for the two experiments were similar to allow a direct
comparison of naltrexone effects on the two measures. Male food-deprived C57BL/6
mice responded for ethanol during either preprandial (low thirst, high hunger
motivation) or postprandial (high thirst, low hunger motivation tests). The
reinforcing value of ethanol relative to water was greater during the preprandial
tests; however, the amounts of ethanol consumed was greater during the
postprandial tests, with some mice becoming unconscious during the 15-min test
session. Naltrexone produced dose-responsive reductions in responding for ethanol
under either testing condition. During postprandial tests, naltrexone reduced
responding for ethanol reward at a dose (1.25 mg/kg) that had little effect on
responding for water reward, suggesting some selectivity for ethanol reward. In
addition, doses of naltrexone that reduced responding for ethanol rewards did not
alter the discrimination of ethanol (g/kg) in an operant discrimination task, but
did reduce the total number of responses made during these tests. Thus, under
similar motivational and dosing conditions, the opiate antagonist attenuated the
reinforcing, but not the discriminative properties of ethanol, suggesting that
the latter is mediated by either different or additional neural mechanisms in
C57BL/6 mice.
PMID- 10195819
TI - Thymocyte development in male fetal alcohol-exposed rats.
AB - We previously reported altered responses of thymocytes to mitogen stimulation
after fetal alcohol exposure (FAE) in prepubertal male Sprague-Dawley rats. The
purpose of this study was to examine the effect of FAE on the developmental
pattern of thymocyte subsets. In the first experiment, we found that the
proportion of double-labeled CD4+CD8+ thymocytes is identical in fetal alcohol
exposed (E) and control (C) animals at 34 and 45 days of age. In the second
experiment--at 20, 28, 35, and 48 days of age--we examined the proportion of CD4+
and CD8+ thymocytes that express or are devoid of the maturational markers, the
alpha/beta configuration of the T-cell receptor (TcR), and the restriction
fragment C of the common leukocyte antigen (CD45RC). We found significant age
dependent effects on the numbers of total double-positive CD4-TcR and CD8-TcR or
CD45RC thymocytes, and significantly lower numbers of total CD4+ and CD8+ cells
in E than in C rats throughout this period--a finding consistent with the
significantly lower total number of thymocytes in E than in C rats. The
developmental patterns for both markers were similar in E and C groups, in both
the rising (days 20 to 28) and declining (days 35 to 48) phases. However, on day
35, E rats had significantly lower numbers of double-positive CD8-TcR and CD8
CD45RC cells than C rats. It therefore seems that FAE tends to accelerate the
decline of double-positive CD8-TcR and CD8-CD45RC cells. The contribution of this
phenotypic change to the thymic functional alterations induced by FAE remains to
be determined.
PMID- 10195820
TI - Glucose metabolism, insulin-like growth factor-I, and insulin-like growth factor
binding protein-1 after alcohol withdrawal.
AB - Alcohol abusers often present with deteriorated glucose metabolism and insulin
resistance. Changes in other glucoregulators, such as insulin-like growth factor
I (IGF-I) and IGF-binding protein-1 (IGFBP-1) may also be related to alcohol
abuse. We studied the effects of alcohol withdrawal on blood glucose, serum
insulin and C-peptide, and plasma IGF-I and IGFBP-1 levels in 27 noncirrhotic
male alcoholics aged 43 +/- 9.0 (mean +/- SD) years on four consecutive days
immediately after withdrawal. A 4-day monitoring period was conducted in four
healthy nonalcoholic control men. The groups were similar in age and body mass
index. Glucose, insulin, IGF-I, and IGFBP-1 did not differ significantly between
the groups at the baseline, but C-peptide was higher in alcoholics (p < 0.01).
After alcohol withdrawal, serum insulin and C-peptide levels increased in close
correlation with each other (r = 0.82, p < 0.001). During the 4-day observation
period in alcoholics, IGFBP-1 levels declined by 59%, whereas IGF-I increased by
41% (p < 0.001 for both comparisons). The change in insulin correlated inversely
with the change in IGFBP-1 levels (r = -0.39, p < 0.05). In the control group,
glucose, insulin, IGF-I, and IGFBP-1 remained unchanged during the 4-day
monitoring period, whereas some reduction was observed in C-peptide. In
conclusion, alcohol withdrawal enhances insulin production, as seen in increased
C-peptide levels. An inverse correlation between the changes in insulin and that
in IGFBP-1 might suggest that inhibition of IGFBP-1 by insulin remains largely
unchanged during the acute phase of alcohol withdrawal.
PMID- 10195821
TI - Children of alcoholics exhibit attenuated cognitive impairment during an ethanol
challenge.
AB - In an attempt to identify markers potentially related to the development of
problem drinking, we examined cognitive functioning in children of alcoholics
(COAs) and children of nonalcoholics, both while sober and after consuming 0.85
ml/kg of ethanol. Consonant with previous research indicating that COAs exhibit
less intense responses to alcohol, we predicted that COAs would experience
attenuated cognitive deficits while intoxicated. Male (n = 71) and female (n =
29) college students completed tests of contextual and rote memory recall in a
repeated-measures design. Findings indicated that intoxication impaired both
memory and attentional capacities, and that COAs exhibited attenuated cognitive
deficits relative to children of nonalcoholics. Results were consistent with
previous research demonstrating attenuated responses to alcohol in COAs.
Potential mechanisms for the pathogenesis of problem drinking are discussed.
PMID- 10195822
TI - The Tridimensional Personality Questionnaire as a predictor of relapse in
detoxified alcohol dependents. The European Fluvoxamine in Alcoholism Study
Group.
AB - Personality traits have been found as strong predictors for treatment response in
different psychiatric disorders. We administered the Tridimensional Personality
Questionnaire, which measures the three personality dimensions: novelty seeking,
harm avoidance (HA), and reward dependence, as introduced by Cloninger in a
multicenter study (11 centers in the United Kingdom, Eire, Switzerland, and
Austria) with detoxified alcohol-dependent patients (n = 521). The objective of
this study was to evaluate a possible predictive value of these three dimensions
on relapse over 1 -year follow up. A logistic regression analysis showed that
novelty seeking is a strong predictor for relapse in detoxified male alcoholics
(p = 0.0007; p values adjusted for treatment), but not in females. In both sexes,
HA and reward dependence were of no predictive value. However, we found a trend
for significance of HA for predicting "early" relapse (4 weeks) in females (p =
0.074). Our results show that Tridimensional Personality Questionnaire
personality traits have direct clinical applications for prediction of relapse in
detoxified alcohol dependents and indicate the necessity of additional
therapeutic treatment in risk groups.
PMID- 10195823
TI - Ethyl linoleate in meconium: a biomarker for prenatal ethanol exposure.
AB - BACKGROUND: Fetal alcohol syndrome, fetal alcohol effects, alcohol-related
neurodevelopmental disorder, and alcohol-related birth defects, all terms
referring to the spectrum of consequences of in utero exposure to ethanol, are a
major public health burden. There is currently no laboratory test to identify
newborns exposed to ethanol in utero. Meconium was analyzed for ethyl linoleate,
a metabolite of ethanol, as a biological marker for fetal ethanol exposure.
METHODS: Samples of meconium were obtained from 248 infants and analyzed for
fatty acid ethyl esters. Detailed maternal alcohol, tobacco, and drug use
histories were obtained within 1 month of giving birth. RESULTS: The detection of
ethyl linoleate in meconium was called a positive test. The mean number of drinks
reported per week in the month before pregnancy, the first trimester, and overall
were significantly higher in the positive group (unadjusted: 9.2 +/- 1.9 vs. 4.3
+/- 1.4, p = 0.004; 7.3 +/- 1.7 vs. 3.8 +/- 1.2, p = 0.03; and 6.1 +/- 1.3 vs.
3.0 +/- 1.0, p = 0.006). A positive test was not associated with marijuana,
cocaine, or tobacco use. Sensitivity and specificity of the test were 72% and 51%
to distinguish women who reported 1 or more drinks/week in the third trimester
from women who denied use, and 68% and 48% to distinguish women who used > or =1
drink/week from women who used <1 drink/week in the month before pregnancy.
CONCLUSIONS: The presence of ethyl linoleate in meconium is the first reported
biological marker for maternal ethanol use during pregnancy. Because of the
inherent inaccuracy associated with the use of self-reporting, the establishment
of true values of sensitivity and specificity will require validation where the
presence, quantity, and timing of exposure to alcohol is known. Further
validation of this marker will permit identification and intervention of at-risk
infants.
PMID- 10195824
TI - A twin study of genetic influences on the acute adaptation of the EEG to alcohol.
AB - A two-dose alcohol challenge protocol was used to study genetic influences on the
acute adaptation of the EEG to alcohol in 53 monozygotic and 38 same-sex
dizygotic Caucasian twin pairs averaging 30 years of age. Equal doses of alcohol
were administered at 10:00 and 11:00 AM, yielding mean peak breath alcohol
concentrations of 0.057% and 0.099%, respectively. Eyes-closed, resting EEG was
recorded four times: at baseline; on the ascending limb of the overall experiment
at a breath alcohol concentration (BrAC) near 0.06%; on the descending limb at a
BrAC near the value when the subject's EEG was obtained on the ascending limb;
and, finally, when the BrAC fell to 0.02%. Genetic analyses of log-transformed
values of total spectral power (L10TSP) and spectral band power (L10SBP) were
performed on EEG spectra averaged across all 17 scalp lead locations. After
adjusting for body weight, a significant fraction of population variance in
L10TSP was attributable to genetic influence: H2 values for TSP were 0.73, 0.72,
and 0.73 at the three postalcohol EEG recordings, respectively. Similar findings
pertained to each L10SBP at each postalcohol recording, except forthe delta band.
The change in postethanol EEG power was examined for evidence that genes
influence acute adaptations in brain function. Descending-minus-ascending limb
L10TSP was normalized by the individual's ascending limb L10TSP to minimize
nonalcohol-related effects that can influence both measurements. Earlier analyses
of the same sample's initial EEG response to alcohol noted a substantial increase
in the ascending limb EEG power, compared with baseline. Thus, positive values of
the postethanol change denote a progression away from baseline attributable to
acute sensitization to alcohol; negative values signify a return toward baseline
values suggesting acute tolerance to alcohol. Genetic analysis of the normalized
difference in L10TSP had a highly significant H2 value of 0.70, indicating that
both acute tolerance and acute sensitization to alcohol may represent adaptations
reflecting substantial heritable influence. Slightly smaller, but significant
values of H2 for the normalized difference in L10SPB were observed for delta,
alpha-slow and beta-slow frequency bands. In contrast, H2 for the differences
between the final and ascending limb EEG power were not significant, except for
the theta band. Thus, heritable drowsiness may have contributed to detection of
genetic influences on acute adaptation, but represent a potential confound only
in the theta band.
PMID- 10195825
TI - Variable dose naltrexone-induced hypothalamic-pituitary-adrenal stimulation in
abstinent alcoholics: a preliminary study.
AB - Opiate antagonists have been found to stimulate the hypothalamic-pituitary
adrenal axis. However, despite established usefulness in the management of
alcoholism, systematic, oral dose-titrated natrexone-induced hypothalamic
pituitary-adrenal stimulation has never been studied in alcoholics. Six patients
(5 males, 1 female) with DSM-IV alcohol dependence, who were at least 4 weeks
abstinent from any alcohol [mean 55 days (+/-SE 7.5)], were given four challenges
of oral naltrexone (0, 25, 50, and 100 mg) in a randomized order at least 3 days
apart, after an overnight fast. Naltrexone was administered at 9 AM; serum ACTH,
cortisol, and prolactin were measured at time 0 and at 9 time points over the
next 4 hr. Subjects also filled out a side effect questionnaire and an alcohol
urge questionnaire. Physiological measurements of blood pressure and pulse rate
were taken at the same time points. Repeated-measures ANOVA of the changes in
serum ACTHs over time revealed a significant effect of drug (placebo vs. any dose
of naltrexone) (p < 0.05). Post-hoc analysis revealed a significant difference
between placebo and the 25 mg dose (p < 0.01), the 50 mg dose (p < 0.01), but no
significance between the placebo and the 100 mg dose (p = 0.1). A repeated
measures ANOVA of the changes in serum cortisols over time revealed a significant
effect of drug (p < 0.01). Post-hoc analysis revealed a significant difference
between placebo and the 25 mg dose (p < 0.01), between placebo and the 50 mg dose
(p < 0.05), and placebo and the 100 mg dose (p < 0.01). There was a significant
between dose difference in pulse rate changes over baseline (p < 0.01), and post
hoc analysis revealed a significant diminution in pulse rate at the 100 mg dose
relative to placebo (p < 0.001), and to the other doses. There were no
significant differences in reported side effects, alcohol urge questionnaire
scores, or in other physiological measurements between doses. These data suggest
a significant rise in ACTH and cortisol in response to naltrexone in alcoholics
compared with placebo, with no differences between 25 mg, 50 mg, and 100 mg
doses, and a significant diminution in pulse rate responses at the 100 mg dose.
PMID- 10195826
TI - Alcoholic pancreatitis and polymorphisms of the variable length polythymidine
tract in the cystic fibrosis gene.
AB - BACKGROUND: The observation that only a minority of alcoholics develops clinical
pancreatic disease has led to a search for a predisposing factor to the disease.
One possible predisposing factor is mutation of the cystic fibrosis transmembrane
conductance regulator (CFTR) gene as cystic fibrosis leads to pancreatic injury.
We have recently demonstrated that 15 common CFTR mutations are not found in
patients with alcoholic pancreatitis. Another common polymorphism of the CFTR
gene has recently been implicated in the pathogenesis of idiopathic chronic
pancreatitis, the 5T variant of the variable length polythymidine tract in intron
8 (the normal genotypes are 7T and 9T). The 5T variant inhibits transcription of
exon 9 resulting in a CFTR protein lacking chloride channel activity. The aim of
this study was to determine whether the 5T variant is associated with alcoholic
pancreatitis. METHODS: Fifty-two patients with alcoholic pancreatitis were
identified using standardized diagnostic criteria. Fifty alcoholics without
pancreatitis were also studied as controls. Genomic DNA was extracted from
peripheral blood leukocytes and the polythymidine tract of intron 8 was amplified
by nested polymerase chain reaction using established primers. The polymerase
chain reaction products were digested with MseI, separated by electrophoresis on
15% polyacrylamide gels and genotypes assigned by comparison with known positive
controls. RESULTS: The 5T allele we found in only two patients with alcoholic
pancreatitis (3.9% of th index group; 95% confidence intervals 0-10%) and in
seven alco holic controls. Allele frequencies for 5T, 7T, and 9T in patients with
alcoholic pancreatitis were 1.9%, 85.6%, and 12.5%, respectively These did not
differ from the allele frequencies in alcoholic controls (7%, 79%, and 14% for
5T, 7T, and 9T, respectively). CONCLUSION: The 5T allele was not associated with
alcoholic pancreatitis. Individual susceptibility to this disease remains
unexplained.
PMID- 10195827
TI - Parallels to early onset alcohol use in the relationship of early onset smoking
with drug use and DSM-IV drug and depressive disorders: findings from the
National Longitudinal Epidemiologic Survey.
AB - This paper endeavored to determine (1) if early onset of regular tobacco use is
as predictive of drug use and depressive disorders as it is of alcohol use
disorders; and (2) if a biological commonality, as measured by a family history
of alcoholism and both early onset and severity of disease, among all three
disorders can be evidenced in a large nationally representative sample.
Prevalences of lifetime drug use, drug abuse and dependence, and major depressive
disorders, as well as indices of their severity, were compared among smoking
groups defined by age at onset of regular tobacco use and among nonsmokers.
Linear logistic regression analyses, controlling for important covariates,
including a family history positive for alcoholism, were conducted to assess the
relationship between age at smoking onset and drug use, abuse and dependence, as
well as depressive disorders. Both objectives were met. Moreover, results suggest
that smoking may play an equally, if not even more, insidious role than drinking
in the use and development of dependence on illicit substances and depression.
PMID- 10195828
TI - Drinking patterns and problems: a comparison of two black primary care samples in
two regions.
AB - This paper explores the effect of regional ("wet" vs. "dry") variation in
drinking patterns and problems on the prevalence of alcohol-related problems
among those seeking care in primary care settings. A sample of black primary care
patients interviewed in Hinds County, MS (n = 740) and in Contra Costa County, CA
(n = 93) are compared on quantity and frequency of usual drinking, drunkenness,
consequences of drinking, and alcohol dependence. Controlling for demographic
differences in logistic regression analysis, drinkers in Contra Costa, while no
more likely to report heavy drinking, were four times more likely to report
alcohol-related consequences, more than five times more likely to report alcohol
dependence experiences, and more than nine and a half times more likely to report
ever having had treatment for an alcohol problem than those in Hinds County. Data
suggest that regional variations in drinking patterns may be reflected in alcohol
involvement in primary care caseloads, and that the large variation in the
prevalence of alcohol-related problems found in primary care settings may, in
part, be attributable to this. All primary care settings do not appear to hold
equal promise for screening for and intervening with problem drinking, and
further research is needed in determining those settings that provide the
greatest potential for targeting prevention efforts.
PMID- 10195829
TI - A comparative evaluation of substance abuse treatment: I. Treatment orientation,
amount of care, and 1-year outcomes.
AB - This article first explains the conceptual framework and plan of a naturalistic,
multisite evaluation of Department of Veterans Affairs (VA) substance abuse
treatment programs. It then examines the effectiveness of an index episode of
inpatient treatment and the effectiveness of continuing outpatient care and
participation in self-help groups. The study was conducted among 3018 patients
from 15 VA programs that emphasized 12-Step, cognitive-behavioral (CB), or
eclectic treatment. Casemix-adjusted 1-year outcomes showed that patients in 12
Step programs were the most likely to be abstinent, free of substance abuse
problems, and employed at the 1-year follow-up. Patients who obtained more
regular and more intensive outpatient mental health care, and those who
participated more in 12-Step self-help groups, were more likely to be abstinent
and free of substance use problems at the 1-year follow-up. These findings
support the effectiveness of 12-Step treatment and show that patients with
substance use disorders who become more involved in outpatient care and self-help
groups tend to experience better short-term substance use outcomes. Subsequent
papers in this section focus on the proximal outcomes of treatment, patients with
psychiatric as well as substance use disorders, patient-treatment matching
effects, and the link between program treatment orientation and patients'
involvement in and the influence of 12-Step self-help groups.
PMID- 10195830
TI - A comparative evaluation of substance abuse treatment: II. Linking proximal
outcomes of 12-step and cognitive-behavioral treatment to substance use outcomes.
AB - This study examines the linkages in the treatment process chains that are thought
to underlie two prevalent approaches to substance abuse treatment, traditional 12
Step treatment and cognitive-behavioral treatment. The focus is on the "proximal
outcomes" specified by the two treatment approaches and their relation to
"ultimate" substance use outcomes assessed at a 1-year follow-up. A total of 2687
men who received treatment in 15 Department of Veterans Affairs substance abuse
treatment programs were assessed at treatment entry, at or near discharge, and at
a 1-year follow-up. Based on the results of factor analyses, composite proximal
outcomes variables were constructed to assess 12-Step cognitions, 12-Step
behaviors, cognitive-behavioral beliefs, substance-specific coping, and general
coping. Correlation analyses indicated that some of the proximal outcome
composites assessed at treatment discharge were linked to 1-year outcomes, but
the relationships were weak (r = .09 to .15). At follow-up, the cross-sectional
relationships between the proximal outcome composites and two substance use
outcomes were stronger, but still modest in magnitude (r = .16 to .39). The weak
predictive findings suggest some mechanism is needed to sustain treatment-induced
change on proximal outcomes so that positive ultimate outcomes can be achieved
more frequently. In this regard, participation in continuing care was associated
with enhanced maintenance of treatment gains on proximal outcomes. However, the
modest cross-sectional relationships between proximal and substance use outcomes
at follow-up suggest that the theories on which 12-Step and cognitive-behavioral
substance abuse treatments are based are not sufficiently comprehensive.
PMID- 10195831
TI - A comparative evaluation of substance abuse treatment III. Examining mechanisms
underlying patient-treatment matching hypotheses for 12-step and cognitive
behavioral treatments for substance abuse.
AB - This study examined several hypotheses for matching patients to 12-Step and
cognitive-behavioral (CB) treatments in a multisite evaluation of VA inpatient
substance abuse programs. A total of 804 male patients in five 12-Step programs,
and 1069 male patients in five CB programs completed an intake, discharge, and 1
year follow-up questionnaire. The findings did not support the notion that
certain patient characteristics would differentially predict better outcomes
after 12-Step and CB treatment This conclusion held when the purest 12-Step and
CB programs were used, and when patients who received the full dose of treatment
(i.e., treatment completers) were examined separately. Process analyses of the
hypothesized mechanisms underlying the patient-treatment matching effects did not
yield the expected links among patient characteristics, proximal outcomes, and 1
year outcomes. Our conclusion is that there is no advantage to matching men with
substance abuse problems to 12-Step or CB treatments based on the patient
attributes measured here.
PMID- 10195832
TI - A comparative evaluation of substance abuse treatment IV. The effect of comorbid
psychiatric diagnoses on amount of treatment, continuing care, and 1-year
outcomes.
AB - Recent surveys of the substance abuse patient population have shown a striking
increase in the proportion of patients with a comorbid psychiatric disorder. In
this study, patients with substance abuse and psychotic, anxiety/depressive, or
personality disorders were compared with patients with only substance use
disorders on treatment experiences and outcomes. Regardless of dual diagnosis
status, patients generally improved on both substance use and social functioning
outcomes after substance abuse treatment. At the 1-year follow-up, dually
diagnosed patients, and patients with only substance use disorders, had
comparable substance use outcomes. However, patients with major psychiatric
disorders, specifically psychotic and anxiety/depressive disorders, fared worse
on psychological symptoms and employment outcomes than did patients with
personality disorders and only substance use disorders. Although there were some
group differences on the amount of index treatment received and continuing care,
the overall pattern of relationships between treatment variables and outcomes was
comparable for the patient groups. In addition, there was no diagnostic group by
treatment orientation matching effects, which indicated that the dual diagnosis
patient groups improved as much in 12-Step as in cognitive-behavioral substance
abuse programs.
PMID- 10195833
TI - A comparative evaluation of substance abuse treatment: V. Substance abuse
treatment can enhance the effectiveness of self-help groups.
AB - Affiliation with Alcoholics Anonymous (AA) and other 12-Step self-help groups is
becoming more common at the same time as professional substance abuse treatment
services are becoming less available and of shorter duration. As a result of
these two trends, patients' outcomes may be increasingly influenced by the degree
to which professional treatment programs help patients take maximum advantage of
self-help groups. The present study of 3018 treated veterans examined how the
theoretical orientation of a substance abuse treatment program affects (1) the
proportion of its patients that participate in self-help groups, and, (2) the
degree of benefit patients derive from participation in self-help groups.
Patients treated in 12-Step and eclectic treatment programs had higher rates of
subsequent participation in 12-Step self-help groups than did patients treated in
cognitive behavioral programs. Furthermore, the theoretical orientation of
treatment moderated the outcome of self-help group participation: As the degree
of programs' emphasis on 12-Step approaches increased, the positive relationships
of 12-Step group participation to better substance use and psychological outcomes
became stronger. Hence, it appears that 12-Step oriented treatment programs
enhance the effectiveness of 12-Step self-help groups. Findings are discussed in
terms of implications for clinical practice and for future evaluations of the
combined effects of treatment and self-help groups.
PMID- 10195834
TI - Efficacy and effectiveness: complementary findings from two multisite trials
evaluating outcomes of alcohol treatments differing in theoretical orientations.
PMID- 10195835
TI - Blaming the patient.
PMID- 10195836
TI - Interpreting the anatomy of the meniscofemoral ligaments.
PMID- 10195837
TI - Treatment of displaced fractures of the PIP joint.
PMID- 10195838
TI - Sequential irrigation with common detergents: a promising new method for
decontaminating orthopedic wounds.
AB - This investigation sought to determine the capacity of irrigation solutions in
decontaminating orthopedic wounds challenged with a polymicrobial inoculum. Rats
were divided into two groups, a control group and a treatment group. After
creation of a dorsolumbar incision and placement of a wire through the spinous
process, rats were inoculated with Staphylococcus aureus and Pseudomonas
aeruginosa. Wounds were irrigated with control or treated solutions. At 2 weeks,
cultures were obtained. There were statistically significant differences between
groups regarding total number of culture positive sites (P < 0.001), culture
positive animals (P = 0.02), and quantitative cultures (P < 0.02). Sequential
irrigation with surfactants lowers bacteria counts recovered from polymicrobial
wounds.
PMID- 10195839
TI - Outcome of infected total knee utilizing a staging system for prosthetic joint
infection.
AB - This study reviews, over a 5-year period, the records of 70 consecutive patients
with prosthetic knee infection and evaluates outcomes as a function of a staging
system for prosthetic joint infection. The staging system for prosthetic joint
infection was divided into three main categories that include infection type,
systemic host grade, and local extremity grade. Outcome indices analyzed included
Knee Society Score (KSS), complication rate, amputation rate, and rate of
permanent resection. We show that categorizing and stratifying data for patients
with infected total knee arthroplasty are useful. A universally accepted staging
system would allow for more objective comparisons of treatments and may
eventually define particular treatment regimens for particular classes of
patients.
PMID- 10195840
TI - Septic arthritis.
AB - Hematogenous septic arthritis causes pain and effusion and begins with
inoculation of the joint with bacteria from the intravascular space. The
degradation of ground substance by enzymes released and activated by the acute
inflammatory response, toxins and enzymes produced by the bacteria, and T
lymphocytes stimulated during the delayed immune response, leads to destruction
of the articular cartilage. Whether a given patient will develop a septic joint
or a less severe form of infection is dependent upon characteristics of the
bacterial strain and of the individual's host defenses. Management consists of
systemic antibiotic therapy and decompression of the joint. Synovectomy,
salicylate administration, and continuous passive motion are adjuvant therapies
that have not as yet not been proved to be of benefit.
PMID- 10195841
TI - The value of the pronated-grip view radiograph in assessing dynamic ulnar
positive variance: a case report.
AB - Positive ulnar variance affects surgical decision making when ulnar wrist pain is
refractory to conservative treatment and is either secondary to a posttraumatic
triangular fibrocartilage tear or associated with ulnar impaction syndrome. In
such settings, ulnar recession may be necessary to diminish load transmission
across the ulnocarpal joint. We present a case of a 24-year-old man with chronic
right ulnar wrist pain that illustrates the efficacy of the pronated-grip
radiograph in assessing dynamic ulnar positive variance.
PMID- 10195842
TI - Carry it on the bad side.
PMID- 10195843
TI - Bilateral femoral neck fractures secondary to hypocalcemic seizures in a
skeletally immature patient.
AB - We report the case of an 11-year-old, skeletally immature boy who sustained
bilateral femoral neck fractures during seizure activity. These fractures were
due to hypocalcemia. Although this condition is a rare complication of seizures,
its early recognition and treatment are essential to minimize complications
associated with the delayed treatment of intracapsular hip fractures.
PMID- 10195844
TI - Do all hip fractures result from a fall?
AB - Although most fractures of the proximal femur result from a fall and are related
to direct loads to the hip, there is evidence that intrinsic factors, such as
muscle contraction, can result in a hip fracture and subsequent fall. This paper
reviews the current literature on the various mechanisms of femoral neck and
intertrochanteric fractures.
PMID- 10195845
TI - Delivering bone grafts percutaneously.
AB - Many fractures that require external fixation occur in patients with deficient
bone. To prevent later collapse after the fixation is removed, bone graft
material can be placed into the fracture defect. Mineral can be placed accurately
through a minimal incision by using equipment in the external fixation set.
PMID- 10195846
TI - Immunogenetics of insulin-dependent diabetes mellitus.
PMID- 10195847
TI - Epidemiology of type 1 (insulin-dependent) diabetes mellitus: public health
implications in the Middle East.
AB - Recent estimates suggest that more than 100,000 inhabitants in the Middle East
suffer from type 1 diabetes and that about 6000 subjects in the region develop
the disease each year. This paper illustrates how epidemiological principles and
methods may assist in a rational assessment of the public health impact of type 1
diabetes in the Middle East. Making a series of assumptions, it is estimated that
the future prevalence of type 1 diabetes in the region will increase slightly,
but that the increase may be more pronounced if the disease incidence is
increasing and the prognosis improved. It is recommended that more valid
information is established on the basic epidemiological features of type 1
diabetes in the Middle East, as this will provide the basis of more rational
planning of the current and future diabetes healthcare in the region.
PMID- 10195848
TI - Incidence of insulin-dependent diabetes mellitus in Jordanian children aged 0-14
y during 1992-1996.
AB - An attempt was made by the Jordanian National Center for Diabetes, Endocrine and
Genetic Diseases (NCDEGD) to identify all cases of type 1 diabetes among
Jordanian children aged 0-14 y. Data were obtained retrospectively for the years
1992-1994 and prospectively for the years 1995 and 1996, including full name,
national identifying number, date of birth, date of diagnosis and family history.
The incidence was calculated as the number of cases per 100,000 population,
according to the national census of 1994. The incidence rate for these years
(1992 through 1996) was 2.8, 2.9, 3.2, 3.6 and 3.6 per 100,000 population,
respectively. The male:female ratio was (1:1.03). Seasonal variation at clinical
onset was noticed, with maximum incidence in the winter months and minimum
incidence in the summer months. In conclusion, the incidence of type 1 diabetes
mellitus in Jordanian children aged 0-14 y is among the lowest in the region, but
is rising.
PMID- 10195849
TI - Diabetic ketoacidosis.
AB - Diabetic ketoacidosis (DKA) is a true pediatric and medical emergency. Diagnosis
should be entertained and confirmed within 30 min of presentation. Any delay in
making the diagnosis or instituting fluid and electrolyte correction is likely to
increase morbidity and mortality. Slow and careful monitoring and correction of
water, sodium and potassium levels should decrease DKA-associated problems with
either continuous intravenous low-dose insulin or intramuscular insulin protocols
designed to slowly bring the hyperglycemic and hyperosmotic state towards normal
homeostasis. Special attention should be paid to potassium replenishment. Most
patients do not require bicarbonate replacement. Cerebral edema, when it occurs,
is associated with an approximately 50% morbidity and mortality; therefore, all
attempts should be made at early recognition and prevention since treatment is
less than ideal. Recurrent ketoacidosis is often related to omitted insulin and
major psychosocial turmoil in the family, such as depression substance abuse,
physical and/or sexual abuse. Prevention of recurrent DKA remains a major
challenge for diabetologists and involves detailed assessment of family
psychodynamics plus responsibility for home monitoring and insulin administration
by a mature adult. Sick day guidelines should be taught and reviewed frequently
in an effort to decrease ketoacidosis and metabolic decompensation during
episodes of intercurrent illness.
PMID- 10195850
TI - Modern insulin therapy in children and adolescents.
AB - Clear evidence exists that near-normal blood glucose control will prevent serious
late diabetic complications. This review summarizes the targets for blood glucose
control and discusses why insulin replacement therapy is so complicated in
children and adolescents. It is important that diabetes treatment teams have
excellent knowledge of insulin preparations, insulin pharmacokinetics and action
profiles and the limitations and pitfalls of therapy. This is necessary to be
able to optimize and individualize treatment. A detailed summary of different
insulin regimens is given and discussed to help treatment teams choose a suitable
regimen for the individual patient. The use of home blood glucose measurement is
necessary to reach the targets of treatment. If economic resources are limited,
alternative strategies are suggested. In wealthy countries the lifestyle of
adolescents demands great flexibility and a suggestion for systematic training to
increase flexibility in daily life is presented.
PMID- 10195851
TI - Hypoglycaemia in children with type 1 diabetes mellitus.
AB - Hypoglycaemia is a frequent acute complication of IDDM and is usually defined as
a blood glucose level below 3.0 mmol/l. Hypoglycaemia stimulates several
neuroendocrine responses, such as secretion of glucagon, adrenaline, growth
hormone and cortisol, which are generally increased during this phenomenon. The
true prevalence of hypoglycaemia is not known. Studies of the epidemiology of
severe hypoglycaemia give prevalences ranging from 2.7 to 85.7 episodes per 100
patients per year. The major risk factor for severe hypoglycaemia is
hypoglycaemia unawareness, which occurs particularly in patients with type 1
diabetes of long duration and in those with a history of frequent episodes of
hypoglycaemia. The first step in the management of hypoglycaemia is to check
blood glucose and to treat hypoglycaemia on the basis of symptoms. Hypoglycaemia
requires urgent treatment with a fast-acting carbohydrate or, if severe, with
parenteral glucagon or intravenous glucose. Prevention measures should be
instituted to prevent subsequent episodes, particularly in younger children with
hypoglycaemic seizures or when seizures are recurrent.
PMID- 10195852
TI - Prevention of microvascular complications in diabetic children and adolescents.
AB - Diabetes mellitus causes profound alterations in many body tissues. Microvascular
diabetic complications include diabetic neuropathy, nephropathy and retinopathy.
Nephropathy first becomes manifest with hyperfiltration and microalbuminuria.
These functional changes evolve over several years to a stage of marked
deterioration of renal function. The possible preventive measures are metabolic
control, reduction of dietary protein intake and use of ACE-inhibitors. Metabolic
control is also important for the prevention of diabetic retinopathy. In fact,
patients with HbA1c higher than 10% have an increased risk of progression of
retinopathy. Moreover, an accelerated progression of retinopathy has been
observed in patients with systemic hypertension following the onset of
microalbuminuria. It has been demonstrated that diabetic neuropathy can also be
present during childhood; therefore, it is possible to detect
electrophysiological abnormalities in children and adolescents with IDDM.
Glycaemic and blood pressure control are, so far, the main means for possible
prevention or modification of the natural history of diabetic microvascular
complications. Tight glycaemic control may have beneficial effects for diabetic
neuropathy. In addition, other preventive measures, such as aldose reductase
inhibitors, gangliosides, neurotrophic vitamins, etc., have been studied in the
last years. However, no conclusive results have been obtained so far.
PMID- 10195853
TI - The role of nutrition in prevention of complications in insulin-dependent
diabetes mellitus.
AB - Nutrition management is an integral part of overall diabetic treatment that
includes insulin, physical activity, emotional support and guidance. The aim of
the present study was to evaluate a dietary approach in line with the recommended
dietary allowances in terms of protein, total and saturated fat, carbohydrates as
well as fibre and polyunsaturated fatty acid. A correct dietary approach may help
to prevent and to reduce to a minimum any risk of hyperglycaemia, hypoglycaemia
and important long-term complications such as obesity, hyperlipidaemia and
hypertension, and at the same time normal growth development.
PMID- 10195854
TI - Present and future perspectives on children with type 1 diabetes.
AB - This review presents current achievements in paediatric diabetology and discusses
potential new approaches. Recent multinational investigations have demonstrated
that in spite of multidisciplinary diabetes care only one-third of young patients
with diabetes have an HbA1c below 8%, which is associated with a lower risk for
development of secondary complications. Since there is no standard protocol for
the optimal treatment of diabetes in children and adolescents, the therapy has to
be tailored to the individual child's needs, involving not only paediatricians,
but also dieticians, diabetes educators, psychologists and social workers. To
improve the current situation a major goal for the next few years appears to be
the establishment of standards for structure, process and outcome quality in
paediatric diabetology. Future perspectives include possibilities for a cure via
islet- or pancreas transplantation or improved pharmacological therapy following
the introduction of new types of insulin or other beta cell-related peptides as
adjunctive therapy not currently used.
PMID- 10195855
TI - Family management of insulin-dependent diabetes mellitus: a practical problem
solving approach.
AB - Insulin-dependent diabetes mellitus (IDDM) as a chronic and potentially life
threatening condition, may have a devastating acute and long-term effect on the
patient and his or her family. IDMM's management should include the following
components: (a) establishment of a co-operative relationship amongst the patient,
his or her family and the members of the diabetes team, (b) emphasis on the
promotion of problem-solving strategies, (c) sufficient emotional and
psychological support and proper education and training concerning diabetic
control, provided not only to the patient but to all the family members involved
in his or her care. The treatment regimen, as well as the above mentioned
components of IDMM management should be tailored to the individual's specific
needs, developmental stage and a level of adjustment. These facilitating
conditions can have a positive and long-standing effect on the individual's
capacity to cope efficiently in order to improve quality of life and obtain
adjustment.
PMID- 10195856
TI - Percutaneous chemolysis--an important tool in the treatment of urolithiasis.
AB - Persistent residual calculi after therapy, i.e. extracorporeal shock wave
lithotripsy (ESWL), percutaneous nephrolitholapaxy (PNL), as well as pyelo- and
nephrolithotomy are big problems in the treatment of urolithiasis. Furthermore,
the therapy of stones is problematic in patients with inadequate drainage,
impaired kidney function, or with high risks against anaesthetics. Between 1991
and 1997 percutaneous antegrade chemolysis was carried out in eleven patients. In
nine of them complete dissolution of stones was achieved. In two further cases,
in which calcium oxalate was the main component of the stones, chemolysis was
unsuccessful. Through our own cases and under consideration of the literature, we
will show that percutaneous chemolysis in these cases is useful and effective in
the treatment of urolithiasis.
PMID- 10195857
TI - The effect of ESWL of renal calculi on pancreatic function.
AB - Fifteen patients were treated by ESWL for renal calculi. The sagittal size of the
head, neck and tail of the pancreas, and serum amylase, insulin, c-peptide and 24
hour urine amylase levels were estimated pre and post-treatment. Serum glucose,
serum amylase and urinary levels remained within normal limits. Serum levels of
insulin, c-peptide and the size of the gland increased but this was not
statistically significant. There may be some danger to the pancreas during ESWL
as there are some morphological changes even though there are no evident peptide
changes. Caution should be taken if patients have a history of pancreatitis.
PMID- 10195858
TI - The patients perspective of extracorporeal shock wave lithotripsy.
AB - We studied the effect of a single analgesic regime for outpatient lithotripsy on
the patient's perception of pain and the disruption of their normal activities by
sending a postal questionnaire to 200 patients. Results showed that 15% of
patients received insufficient analgesia during ESWL, 25% considered treatment
painful, 6.8% had side effects from analgesia, 18% had delayed return to their
normal activities and 33% contacted their doctor within a week of lithotripsy
with problems related to it. This study shows that analgesic requirements of
patients treated with modern lithotriptors are underestimated. This can be
avoided by tailoring analgesia to individual needs and better patient
communication.
PMID- 10195859
TI - Bellini duct (collecting duct) carcinoma of the kidney.
AB - Carcinoma of the collecting ducts, or Bellini carcinoma, is a rare renal tumour
and, unlike most renal cell carcinomas, it derives from distal tubules. It
displays highly aggressive behaviour and has a poor prognosis. In this study, the
authors present three cases which they observed over the past three years.
PMID- 10195860
TI - Prognostic factors and the role of nephrectomy in metastatic renal cell
carcinoma.
AB - The objective of this study was to evaluate the prognostic factors and role of
nephrectomy in metastatic renal cell carcinoma. We reviewed 62 cases of
metastatic renal cell carcinoma (RCC) at presentation to document the factors
influencing the survival and to evaluate the role of nephrectomy. Sex and age of
the patients, size of the primary tumour, site and number of the metastases,
nephrectomy, cell type and grade of the tumour and type of the medical treatment
were analyzed as prognostic factors. The age and sex of the patients, cell type
and type of the medical treatment did not appear to be significant predictors of
prognosis. However, improved survival was correlated with tumours < or =7 cm in
diameter, low grade tumours, metastasis limited to single organ and removal of
the primary tumour. When these parameters were analyzed in a combined manner
patients who had undergone nephrectomy showed consistently longer survival. We
suggest that nephrectomy should be considered in all patients with metastatic
RCC, as long as the morbidity of the operation is predicted to be acceptable.
PMID- 10195861
TI - A rare complication of renal biopsy in a child with membranoproliferative
glomerulonephritis.
AB - Percutaneous renal biopsy is essential for the definitive diagnosis of chronic
glomerulonephritis. Large arteriovenous fistula (AVF) which is a rare
complication of native renal biopsy is generally diagnosed in the first weeks
after the procedure. We present a childhood membranoproliferative
glomerulonephritis case with an enormous AVF presenting with severe hypertension
15 months after the biopsy that was successfully embolized. In conclusion, AVF
must be considered in children having chronic glomerulonephritides even if
hypertension appears late after the renal biopsy.
PMID- 10195862
TI - An obvious upper tract lesion?
PMID- 10195863
TI - Pulmonary function after posterior retroperitoneoscopic surgery.
AB - Pulmonary function tests were performed in 12 patients who underwent posterior
retroperitoneoscopic surgery, before and on the 3rd and 7th days after operation.
Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1),
FEV1/FCV, vital capacity (VC), total lung capacity (TLC), residual volume (RV)
and functional residual capacity (FRC) were not significantly different between
before and after surgery. It is assumed that posterior retroperitoneoscopic
surgery could be performed without impairment of pulmonary function after
surgery.
PMID- 10195864
TI - An ureteric polyp removed by ureteroscopy.
AB - A case of benign ureteric polyp resected in one piece endoscopically is reported.
The authors emphasize the role of ureteroscopy in the differential diagnosis of
ureteric tumours. Unnecessary nephroureterectomies or open explorations can be
avoided by the use of this procedure.
PMID- 10195865
TI - Experience with the Dornier lithotriptor MPL 9000-X for the treatment of vesical
lithiasis.
AB - Between February 1994 and March 1995, 52 patients (48 men and 4 women) with
vesical lithiasis were treated by extracorporeal shock wave lithotripsy (ESWL),
using the MPL 9000-X Dornier lithotriptor. Twenty-five patients showed bladder
outlet obstruction. In 9 patients, there was evidence of associated bladder
neuropathy. In 6 patients, calculi presented idiopathically in normal bladders.
Two patients had silent migration of ureteral calculi and increase in bladder
volume, 8 were high risk and 2 others refused other methods of up to date
treatment. Vesical stone sizes ranged from 10 to 22 mm in greatest diameter (mean
15 mm). The treatments were performed without the use of anaesthesia and on an
outpatient basis. Complete fragmentation was achieved after a single session in
46 patients and 3 required 2 sessions. Postoperative adjunctive endourological
procedures included cystoscopy in 9 patients and urethroscopy in 1 patient for
evacuation of stone fragments. The overall stone-free rate was 94.2% (49 out of
52 patients) with ESWL and adjunctive measures as needed. No major complications
were noted. We find ESWL with the MPL 9000-X lithotriptor to be a simple,
effective and safe modality for the treatment of most patients with vesical
lithiasis, especially in high risk patients.
PMID- 10195867
TI - Spontaneous rupture of a bladder with invasive bladder carcinoma.
AB - Spontaneous bladder perforation associated with bladder tumour is extremely rare.
Such patients generally present with the clinical symptoms of an acute abdomen,
and in these settings the mortality rate is very high.
PMID- 10195866
TI - Possible factors affecting response to intravesical bacillus Calmette-Guerin
(Tokyo 172 strain) therapy for carcinoma in situ of the bladder: a multivariate
analysis.
AB - To evaluate clinicopathological factors affecting response to intravesical
instillation therapy with the bacillus Calmette-Guerin (BCG) Tokyo 172 strain for
carcinoma in situ (CIS) of the bladder, we reviewed data for 84 patients treated
between 1985 and 1996. Median follow-up was 56 months. The patients comprised
three groups: primary (only the in situ lesion, 31 patients), subsequent (found
after treatment of a gross neoplasm, 20), and concomitant (found together with a
gross neoplasm, 33). A complete response was found in 62 (74%) of the 84
patients. Intravesical BCG therapy eradicated tumour cells in 74% of the primary
group, 70% of the subsequent group, and 76% of the concomitant group.
Multivariate logistic regression analysis revealed that the presence of gross
haematuria and patient age were significantly associated with a complete response
to the intravesical BCG therapy (p<0.05). On the other hand, gender, irritative
bladder symptoms, type of extent of CIS, histological grade of CIS, BCG dose, and
number of times BCG was given did not exert any significant influence. The 5-year
recurrence rate was 33% for the 62 patients for whom a complete response was once
achieved. Patients aged 60 or older had a higher probability of recurrence than
those less than 60 years of age (p<0.05). Disease progression was found in 13% of
the 84 patients and total cystectomy was performed in 19%. The present finding
that patient age is related to the response to intravesical BCG therapy may point
to a role for the reduced host immunocompetence in elderly individuals.
PMID- 10195868
TI - Estimation of canine prostatic volume: nomogram based on prostatic cubic volume.
AB - To estimate prostate volume in canines, we demonstrated the nomogram based on
prostatic cubic volume. Transrectal ultrasonography (TRUS) was performed in
twenty beagle dogs. Prostatic length (L) and height (H) were determined on
sagittal image, and prostatic width (W) was determined on transaxial image. Data
of one dog, which had asymmetrical shaped prostate, were excluded from the
analysis. Prostate volume was estimated by the following nomogram: Gravimetric
prostatic volume (g) = 0.642 x prostatic cubic volume (cm3) + 1.84 (prostatic
cubic volume = L x H x W cm3, r = 0.997, p<0.001). By substituting the prostatic
height to the average of height, prostatic volume of one dog showing asymmetrical
shape was successfully estimated. We also showed technical points in evaluating
morphology of canine prostate on TRUS. In conclusion, this nomogram is of great
use for directly estimating prostatic volume.
PMID- 10195869
TI - Cells in various benign and malignant conditions of the human prostate express
different antigenic phenotypes.
AB - Prostatic epithelium basically consists of secretory-luminal, basal and endocrine
paracrine cells. Immunohistochemical procedures are frequently used for showing
the cells reflecting different differentiations. In this study, 40 prostatic
tissue specimens submitted to the Department of Pathology of Inonu University,
Research Hospital, between 1991 and 1996 were examined. Half of the cases were
diagnosed as cancer and the other half had various benign lesions. Of the cases
22.5% (n = 9) were needle biopsy material whereas the remainder, 47.5% (n = 19),
were from prostatectomy and 30% (n = 12) were transurethral resection of the
prostate (TURP) specimens. High molecular weight anti-cytokeratin antibodies (HMW
anti-cytokeratin) stained basal cells both in all normal prostatic tissue and
benign prostatic lesions, but in the majority of cancers (70%, n = 14) negative
immunoreactivity was seen. Nevertheless, in some of the cancer cases (30%, n = 6)
basal cell anti-cytokeratin staining was shown. Negative immunoreactivity with
HMW anti-cytokeratin is important in distinguishing between malignant and benign
lesions, whereas positive staining is not every time in favour of benign lesions.
With the usage of prostate specific antigen (PSA) it was seen that all of the
malignant and benign prostatic lesions stained positively. Basal cells in
hyperplastic glands were not stained with this stain. Irregular, and in some
areas, intense (PSA) immunoreactivity is present in precancerous and malignant
lesions. Endocrine cells, which are represented with Chromogranin-A (Chr-A)
immunoreactivity and reflecting neuroendocrine differentiation, are present in
75% (n = 15) of benign lesions and in 50% (n = 10) of cancer cases. It was
thought that the lesser number of these cells in neoplastic lesions in comparison
to the non-tumoral lesions is correlated with the disorder of mechanism that
regulates the cell growth. Both in neoplastic and non-tumoral tissues the
prostatic epithelial cells showed the three markers, namely HMW anti-cytokeratin,
PSA, and Chr-A, which may reflect the multidirectional differentiation of these
cells from a pluripotent origin.
PMID- 10195870
TI - Influence of luteinizing hormone-releasing hormone analogues on serum levels of
prostatic acid phosphatase and prostatic specific antigen in patients with
metastatic carcinoma of the prostate.
AB - Serum concentrations of luteinizing hormone (LH), testosterone, prostatic acid
phosphatase (PAP) and prostatic specific antigen (PSA) were measured in 16
patients with advanced prostatic cancer before and after treatment with
luteinizing hormone-releasing hormone (LHRH) analogue. An initial rise of serum
LH and testosterone levels was observed on day 2 of the treatment. Subsequently,
serum concentrations of PAP and PSA showed a transient increase on day 5 of the
treatment. This indicates that LHRH analogues had better be given in combination
with antiandrogens in patients with metastatic carcinoma of the prostate.
PMID- 10195871
TI - Effect of long-term alcohol abuse on male sexual function and serum gonadal
hormone levels.
AB - PURPOSE: The relationship between chronic alcohol abuse and male sexual
dysfunction and pituitary gonadal function abnormalities remains uncertain. The
purpose of this study was to assess the effect of chronic alcoholism on sexual
functions and serum hormone levels. MATERIALS AND METHODS: Forty-five chronically
alcoholic men and a control group of thirty healthy non-alcoholic volunteers were
enrolled in the study. Each of the men in the study and control group were
interviewed according to a sexual dysfunction questionnaire by an urologist.
Blood samples were collected for evaluation of hormone levels. Sera were stored
at -70 degrees C for analysis. RESULTS: The sexual desire and erection scores of
alcoholic men were not statistically different from those of the control group.
Fourteen out of the 45 alcoholic men complained of loss of erection during sexual
activity. No significant difference in hormone levels between groups was found
except for FSH. CONCLUSION: In the absence of hepatic and gonadal failure in
chronically alcoholic men, there is no significant difference in serum hormonal
levels, sexual dysfunction form, and sexual functions between alcoholics and
normal healthy non-alcoholic men.
PMID- 10195872
TI - Fracture of the penis.
AB - Fracture of the penis is a rare condition. The fracture is easy to recognize but
treatment remains controversial. Between December 1991 and January 1997, eleven
patients underwent emergency operation on the first day after penile fracture.
Our operative plan consisted of immediate exploration, identification,
debridement and primary repair of the tear in the tunica albuginea. The patients'
mean age was 27 years (range 21-38 yrs.). Penile fracture was due to sexual
manoeuvres in 8, manipulation in 2 and fall onto erect penis in one of 11
patients. The mean hospitalization time was 2.2 days (range 1 to 3 days). There
was no significant early postoperative complication except wound infection in one
patient. In the first postoperative month, there was a residual fibrosis due to
nonabsorbable sutures in one patient and mild pain during coitus in the other
one. All patients had full erection and no patient needed additional treatment.
To avoid serious complications and preserve penile functions immediate surgical
intervention is recommended.
PMID- 10195873
TI - The importance of obesity and hyperlipidaemia in patients with renal transplants.
AB - The authors studied dyslipidaemia and "obesity" in 137 patients (87 males and 50
females) following cadaver renal transplantation with regard to the applied
immunosuppressive treatment and the patients' hypertension. The most extreme
dyslipidaemic values, the highest levels of total cholesterol, LDL and Apo were
found 6 to 18 months after successful transplantation; these values were
significantly higher in women than in men. While in the dialysis programme only
21.89% of the patients had BMI values higher than 25.1 kg/m2, after
transplantation their proportion was 36.49%. In addition to hyperlipidaemia,
hyperuricaemia was encountered in 39.42%, erythrocytosis in 8.76% and diabetes
mellitus in 9.48%, respectively. In the group of patients treated only with
Cyclosporine-A the incidence of hyperlipidaemia and hypertension was
significantly lower than in those receiving a combination of either
corticosteroids and Cyclosporine-A or corticosteroids, Cyclosporine-A and
azathioprine. There was a close relationship between the unfavourable tendency of
obesity and the measured hyperlipidaemia. On the other hand, the extent of
proteinuria did not always have a positive correlation with the increase of BMI
and body weight, the severity of hypertension and hyperlipidaemia. The authors
emphasize the importance of a systematic control of the lipid levels, the
significance of a diet with an adequate carbohydrate and lipid content, and the
necessity of avoiding obesity by selecting the optimal immunosuppressive
treatment.
PMID- 10195874
TI - Cardiovascular risk factors and diseases after renal transplantation.
AB - Cardiovascular disease is a leading cause of death after renal transplantation
(tpx), and the incidence is considerably higher than in the general population.
OBJECTIVE: To evaluate the incidence of atherosclerotic cardiovascular
complications after tpx, the prevalence of cardiovascular risk factors, prior to
and following tpx, and the association between the risk factors and
complications. PATIENTS AND METHODS: Analysis of atherosclerotic cardiovascular
diseases (coronary artery disease, cerebral and peripheral vascular disease) and
cardiovascular risk factors before and after transplantation in 427 renal
transplant recipients between 1987 and 1992 (mean age at transplantation 45+/-12
years, 58% male, 7% diabetics) with a mean post-transplant follow-up of 29+/-20
months. RESULTS: Following tpx 11.7% developed atherosclerotic cardiovascular
diseases, the majority coronary artery disease (9.8%). The comparison of risk
factors 12 months before and 24 months following transplantation showed:
prevalence of systemic hypertension (from 73% to 85%), diabetes mellitus (from 7%
to 16%) and obesity with a body mass index >25 kg/m2 (from 26% to 48%) had
increased significantly whereas the number of smokers halved to 20%.
Triglycerides decreased significantly (from 235 mg/dl to 217 mg/dl). Total and
HDL cholesterol rose significantly (from 232 mg/dl to 273 mg/dl and from 47 mg/dl
to 56 mg/dl, respectively). LDL cholesterol increase was significant (from 180
mg/dl to 189 mg/dl). In the univariate analysis, cardiovascular diseases were
significantly associated with male gender, age over 50 years, diabetes mellitus
(DM), smoking, total cholesterol > or=200 mg/dl, LDL cholesterol >180 mg/dl, HDL
cholesterol < or =55 mg/dl, fibrinogen > or =350 mg/dl, body mass index >25
kg/m2, serum uric acid >6.5 mg/dl and with more than two antihypertensive agents
per day. The Cox proportional hazards model revealed DM with a relative risk (RR)
of 4.3, age >50 years (RR=2.7), body mass index >25 kg/m2 (RR=2.6), smoking
(RR=2.5), LDL cholesterol >180 mg/dl (RR=2.3) and uric acid >6.5 mg/dl as
independent risk factors. CONCLUSIONS: The high incidence of cardiovascular
disease following renal transplantation is mainly due to a high prevalence and
accumulation of classical risk factors before and following transplantation.
Future prospective studies should evaluate the success of treatment regarding
reduction of cardiovascular morbidity and mortality in this high risk population.
PMID- 10195875
TI - Effect of dialysis membranes on lipoprotein profile of serum in haemodialysed
patients.
AB - The subjects of the studies were 31 haemodialysed (HD) patients with chronic
renal insufficiency (CRI). In this group of patients the lipoprotein profile was
determined and 8 patients were selected for further studies. During the study the
patients were treated with cuprophane membranes for 6 months. For the next 6
months the same patients were treated using polysulfone dialysers, and for
further 6 months HD with polysulfone dialysers was continued. Patients' sera were
tested after every 6 months of treatment. The delta values were calculated as 6
month HD with polysulfone minus 6-month HD with cuprophane (deltaI) and 12-month
HD with polysulfone minus 6-month HD with polysulfone (deltaII). We concluded
that after long-term HD with low flux polysulfone treatment the lipoprotein
profiles improved, but the mechanism of the process is not clear.
PMID- 10195876
TI - Evaluation of autosomal dominant polycystic kidney disease by DTPA renal
scintigraphy.
AB - Sixty patients with previously documented autosomal dominant polycystic kidney
disease (ADPKD) were investigated using dynamic kidney scintigraphy with 99mTc
diethylenetriaminepentaacetic acid (DTPA). Patients were subdivided in respect of
glomerular filtration rate (GFR) as follows: PKD I group (normal GFR), PKD II
group (moderately reduced GFR), and PKD III (severely reduced GFR). Scintigraphic
features, time activity curves, excretion parameters, global and individual
kidney functions were analyzed. Because of GFR dependent sensitivity, in advanced
renal failure being only 0.1, and low reproducibility (11% intraobserver, 22%
interobserver), 99mTc-DTPA dynamic kidney scintigraphy cannot be generally
recommended for the diagnosis of ADPKD, but has to become a routine method for
functional evaluation of both global and individual renal functions, as well as
degree of excretion disturbances in ADPKD patients.
PMID- 10195877
TI - Use of L-plastin promoter to develop an adenoviral system that confers transgene
expression in ovarian cancer cells but not in normal mesothelial cells.
AB - The objective of this study was to develop an adenoviral vector system that would
generate a pattern of expression of exogenous therapeutic genes appropriate for
the treatment of ovarian cancer. For this purpose, we have generated a
replication-deficient recombinant adenoviral vector, AdLPLacZ, which contains the
human L-plastin (LP) promoter (LP-P) driving the Escherichia coli LacZ gene. LP
is constitutively expressed at high levels in malignant epithelial cells but is
not expressed in normal tissues, except at low levels in mature hematopoietic
cells. Because adenoviral vectors infect early hematopoietic multilineage
precursor cells only poorly or not at all, this vector would be of use in the
peritoneal cavity and in vitro for marrow purging. We first analyzed the
expression of the LacZ reporter gene in ovarian and breast cancer cell lines,
normal fibroblasts, and leukemia cell lines using the adenoviral vector in which
the LacZ gene is governed by the LP-P promoter (AdLPLacZ) or in which the LacZ
gene is governed by the cytomegalovirus (CMV) promoter (AdCMVLacZ). We found
equivalent and high levels of expression of beta-galactosidase (beta-gal) by
AdLPLacZ and AdCMVLacZ vectors in the breast or ovarian cancer cell lines as well
as in a fibrosarcoma cell line, indicating that the adenoviral vectors infected
these cells and expressed their transgenes equally with the LP and CMV promoters.
Expression of the LacZ gene with the CMV vector but not with the LP-P vector was
observed in experiments with normal fibroblasts, indicating that the vectors
infected the cells, but that the LP-P was not active within them. In
hematopoietic cells such as U937 cells, no measurable beta-gal activity was
detected in cells infected either by AdLPLacZ or by AdCMVLacZ, indicating that
the adenoviral vectors were not infecting the cells. Although beta-gal activity
was observed in fresh ascitic ovarian cancer cells after infection with
adenoviral vectors containing CMV or the LP promoters, beta-gal activity was
detected in a portion of a biopsy of normal peritoneum when the tissues were
exposed to the AdCMVLacZ vector, but not when tissues were exposed to the
AdLPLacZ vector. These results suggest that the transcription of therapeutic
genes in cells infected by the AdLP vectors would be restricted to LP expression
positive ovarian carcinoma cells but would not be seen in the normal mesothelial
cells of the peritoneal cavity. This possibility implies that adenoviral vectors
carrying therapeutic genes driven by the LP-P would be of use for the
intracavitary treatment ovarian cancer.
PMID- 10195878
TI - Coacervate microspheres as carriers of recombinant adenoviruses.
AB - The therapeutic utility of recombinant adenoviruses (rAds) is limited in part by
difficulties in directing the viruses to specific sites and by the requirement
for bolus administration, both of which limit the efficiency of target tissue
infection. As a first step toward overcoming these limitations, rAds were
encapsulated in coacervate microspheres comprised of gelatin and alginate
followed by stabilization with calcium ions. Ultrastructural evaluation showed
that the microspheres formed in this manner were 0.8-10 microM in diameter, with
viruses evenly distributed. The microspheres achieved a sustained release of
adenovirus with a nominal loss of bioactivity. The pattern of release and the
total amount of virus released was modified by changes in microsphere
formulation. Administration of the adenovirus-containing microspheres to human
tumor nodules engrafted in mice showed that the viral transgene was transferred
to the tumor cells. It is concluded that coacervate microspheres can be used to
encapsulate bioactive rAd and release it in a time-dependent manner.
PMID- 10195879
TI - Development and application of adenoviral vectors for gene therapy of cancer.
AB - For successful gene vaccination and therapy of cancer, it is essential to develop
gene delivery vectors that can meet clinical and social requirements. The need
for improved vectors was clearly manifested during the peak of the first wave of
gene therapy. Adenoviral (Ad) vectors have recently drawn the attention of many
of those involved in the field of gene therapy for cancer because of their
practical advantages and application potential. Many experiments, innovations,
preclinical studies, and clinical trials have generated an overwhelming amount of
data and literature concerning this vector system. It is hoped that the
comprehensive review presented here, which includes the principles, potential,
capacity, and limitations of the current Ad systems, will help to further the
rational development of the system. The literature in this article is organized
in an attempt to emphasize Ad vector development in the aspects of technical
approaches, practical hurdles and strategies to overcome them, significant
experimental results, recent advances, future directions, etc. The technical
range of this review covers details that are intended to serve as a reference for
advanced technical readers and provide a foundation for initiates in the field of
Ad vector gene therapy. The material presented here is also intended for
nontechnical persons who want to have an overview of the significance and
potential of the technology.
PMID- 10195880
TI - In vivo manipulation of interleukin-2 expression by a retroviral tetracycline
(tet)-regulated system.
AB - We have used the tetracycline (tet)-regulated system as described previously to
evaluate the applicability of controlled gene expression in cancer gene therapy.
As a model gene, we used the human interleukin-2 (IL-2) gene, which has been
placed under the transcriptional control of the tetO/promoter. Human melanoma
cells were transduced by two modified retroviral tet vectors containing the
transactivator regulatory unit and the IL-2 gene driven by the tetO/promoter,
respectively. In the absence of tet, IL-2 expression in the target cells was
stable over several months. IL-2 production was in the range of 40 U/10(6)
cells/24 hours. A fine tuning of IL-2 expression could be achieved by culturing
the transduced cells with increasing doses of tet, whereby a concentration of 500
ng/mL tet in the culture medium abrogated IL-2 expression. Most importantly for
clinical application, IL-2 expression by the transduced melanoma cells could also
be regulated in vivo. When nu/nu mice were inoculated with the transduced tumor
cells, they failed to develop tumors. Instead, the inhibition of IL-2 expression
in the transduced tumor cells by oral administration of tet led to subcutaneous
tumor growth; this growth rate was comparable with the growth rate of
subcutaneously inoculated untransduced parental cells. The finding demonstrates
the applicability of the tet-regulated system in cancer gene therapy.
PMID- 10195881
TI - Experimental gene therapy against subcutaneously implanted glioma with a herpes
simplex virus-defective vector expressing interferon-gamma.
AB - We investigated the feasibility of local treatment or tumor vaccination with a
herpes simplex virus (HSV) type 1-defective vector. The vector was engineered to
express murine interferon-gamma (IFN-gamma) for experimental gene therapy against
mouse glioma Rous sarcoma virus (RSV). The murine IFN-gamma gene was driven by
the cytomegalovirus promoter. The helper virus (tsk) was thermosensitive;
consequently, this vector could only proliferate at 31 degrees C. A high level of
murine IFN-gamma expression was confirmed in vitro and in vivo by
immunohistochemistry using anti-mouse IFN-gamma monoclonal antibody. This
engineered vector (dvHSV/MulFN-gamma) inhibited the proliferation of mouse glioma
RSV cells in vitro, and an intratumoral (i.t.) local injection of the vector
caused i.t. necrosis in vivo. The immunological effect of dvHSV/MulFN-gamma was
also examined in a mouse glioma RSV cell implantation model. A subcutaneous
(s.c.) implant of 1 x 10(6) mouse glioma RSV cells after treatment with
dvHSV/MulFN-gamma was rejected. However, the implant after treatment with an
engineered HSV-defective vector containing an antisense nucleotide sequence of
the murine IFN-gamma gene was not rejected. In addition, in another group of mice
in which RSV cells treated with dvHSV/MulFN-gamma were implanted into a femoral
(s.c.) region and nontreated RSV cells were implanted into a contralateral
femoral (s.c.) region, the implanted RSV cells were rejected. The rejection of
the implanted mouse glioma RSV was blocked by anti-asialo GM1, which was known to
inhibit natural killer cell activity. These results revealed that the HSV
defective vector could realize a high efficiency of transfection to glioma cells
through short-time treatment, and that the IFN-gamma gene transferred to the
cells had the effect of tumor vaccination, which was suggested be related to
natural killer cells. In conclusion, dvHSV/MulFN-gamma may be useful for the gene
therapy of malignant glioma through either i.t. local injection or a practical
tumor vaccination with ex vivo gene transfer.
PMID- 10195882
TI - Combined radiation and p53 gene therapy of malignant glioma cells.
AB - More than half of malignant gliomas reportedly have alterations in the p53 tumor
suppressor gene. Because p53 plays a key role in the cellular response to DNA
damaging agents, we investigated the role of p53 gene therapy before ionizing
radiation in cultured human glioma cells containing normal or mutated p53. Three
established human glioma cell lines expressing the wild-type (U87 MG, p53wt) or
mutant (A172 and U373 MG, p53mut) p53 gene were transduced by recombinant
adenoviral vectors bearing human p53 (Adp53) and Escherichia coli beta
galactosidase genes (AdLacZ, control virus) before radiation (0-20 Gy). Changes
in p53, p21, and Bax expression were studied by Western immunoblotting, whereas
cell cycle alterations and apoptosis were investigated by flow cytometry and
nuclear staining. Survival was assessed by clonogenic assays. Within 48 hours of
Adp53 exposure, all three cell lines demonstrated p53 expression at a viral
multiplicity of infection of 100. p21, which is a p53-inducible downstream
effector gene, was overexpressed, and cells were arrested in the G1 phase. Bax
expression, which is thought to play a role in p53-induced apoptosis, did not
change with either radiation or Adp53. Apoptosis and survival after p53 gene
therapy varied. U87 MG (p53wt) cells showed minimal apoptosis after Adp53,
irradiation, or combined treatments. U373 MG (p53mut) cells underwent massive
apoptosis and died within 48 hours of Adp53 treatment, independent of
irradiation. Surprisingly, A172 (p53mut) cells demonstrated minimal apoptosis
after Adp53 exposure; however, unlike U373 MG cells, apoptosis increased with
radiation dose. Survival of all three cell lines was reduced dramatically after
>10 Gy. Although Adp53 transduction significantly reduced the survival of U373 MG
cells and inhibited A172 growth, it had no effect on the U87 MG cell line.
Transduction with AdLacZ did not affect apoptosis or cell cycle progression and
only minimally affected survival in all cell lines. We conclude that responses to
p53 gene therapy are variable among gliomas and most likely depend upon both
cellular p53 status and as yet ill-defined downstream pathways involving
activation of cell cycle regulatory and apoptotic genes.
PMID- 10195883
TI - Apoptosis induction by E2F-1 via adenoviral-mediated gene transfer results in
growth suppression of head and neck squamous cell carcinoma cell lines.
AB - E2F-1, a transcription factor by discovery, is thought to play a crucial role in
regulating G1/S cell cycle progression. Its activity is modulated by complex
formation with the retinoblastoma protein and related proteins. Overexpression of
E2F-1 has been shown to induce apoptosis in quiescent fibroblasts. We constructed
a recombinant E2F-1 adenovirus to test whether an overexpression of E2F-1 in head
and neck squamous cell carcinoma cell lines would also induce apoptosis. Two cell
lines, Tu-138 and Tu-167, were chosen for use in this study. Both cell lines
harbor p53 mutations but express different levels of the retinoblastoma protein.
Upon E2F-1 adenovirus infection, both cell lines expressed elevated levels of E2F
1 protein and then activated a pRb-chloramphenicol acetyltransferase reporter
construct containing an E2F-1 binding motif. In vitro growth assay demonstrated
that growth suppression by the E2F-1 protein was effective on both cell lines.
Results from DNA fragmentation and terminal deoxynucleotidyl transferase-mediated
deoxyuridine triphosphate-biotin nick end-labeling analyses indicated apoptosis
induction in cells infected with AdCMV-E2F-1. Moreover, ex vivo experiments in
nude mice showed total suppression of tumor growth at sites that received cells
infected AdCMV-E2F-1. An in vivo analysis of apoptosis using in situ end-labeling
further demonstrated the induction of apoptosis by AdCMV-E2F-1 in tumor-bearing
animals. These data indicate that overexpression of E2F-1 via an adenoviral
vector suppresses in vitro and in vivo growth of head and neck squamous carcinoma
cell lines through induction of apoptosis.
PMID- 10195884
TI - Intraperitoneal gene therapy with adenoviral-mediated p53 tumor suppressor gene
for ovarian cancer model in nude mouse.
AB - In an effort to develop a method for better local control of advanced ovarian
cancers, we have established a peritoneal tumor model of ovarian cancer in the
nude mouse and applied intraperitoneal gene therapy with the recombinant
adenoviral-mediated wild-type p53 tumor suppressor gene (Avp53). The results
indicate that: (a) the recombinant adenoviral vector system effectively infected
the tumor and normal cells in the peritoneal cavity; and (b) Avp53 treatment
effectively suppressed the growth of peritoneal tumors and prolonged the survival
of the treated group, especially when the tumor burden was less. These results
suggest that intraperitoneal gene therapy using Avp53 is potentially useful as an
adjuvant therapeutic modality in human ovarian cancer.
PMID- 10195885
TI - Differential chemosensitivity of breast cancer cells to ganciclovir treatment
following adenovirus-mediated herpes simplex virus thymidine kinase gene
transfer.
AB - The development of resistance to radiation and chemotherapeutic agents that cause
DNA damage is a major problem for the treatment of breast and other cancers. The
p53 tumor suppressor gene plays a direct role in the signaling of cell cycle
arrest and apoptosis in response to DNA damage, and p53 gene mutations have been
correlated with increased resistance to DNA-damaging agents. Herpes simplex virus
thymidine kinase (HSV-tk) gene transfer followed by ganciclovir (GCV) treatment
is a novel tumor ablation strategy that has shown good success in a variety of
experimental tumor models. However, GCV cytotoxicity is believed to be mediated
by DNA damage-induced apoptosis, and the relationship between p53 gene status,
p53-mediated apoptosis, and the sensitivity of human tumors to HSV-tk/GCV
treatment has not been firmly established. To address this issue, we compared the
therapeutic efficacy of adenovirus-mediated HSV-tk gene transfer and GCV
treatment in two human breast cancer cell lines: MCF-7 cells, which express wild
type p53, and MDA-MB-468 cells, which express high levels of a mutant p53 (273
Arg-His). Treating MCF-7 cells with AdHSV-tk/GCV led to the predicted increase in
endogenous p53 and p21WAF1/CIP1 protein levels, and apoptosis was observed in a
significant proportion of the target cell population. However, treating MDA-MB
468 cells under the same conditions resulted in a much stronger apoptotic
response in the absence of induction in p21WAF1/CIP1 protein levels. This latter
result suggested that HSV-tk/GCV treatment can activate a strong p53-independent
apoptotic response in tumor cells that lack functional p53. To confirm this
observation, four additional human breast cancer cell lines expressing mutant p53
were examined. Although a significant degree of variability in GCV
chemosensitivity was observed in these cell lines, all displayed a greater
reduction in cell viability than MCF-7 or normal mammary cells treated under the
same conditions. These results suggest that endogenous p53 status does not
correlate with chemosensitivity to HSV-tk/GCV treatment. Furthermore, evidence
for a p53-independent apoptotic response serves to extend the potential of this
therapeutic strategy to tumors that express mutant p53 and that may have
developed resistance to conventional genotoxic agents.
PMID- 10195886
TI - Revisiting the commons: local lessons, global challenges.
AB - In a seminal paper, Garrett Hardin argued in 1968 that users of a commons are
caught in an inevitable process that leads to the destruction of the resources on
which they depend. This article discusses new insights about such problems and
the conditions most likely to favor sustainable uses of common-pool resources.
Some of the most difficult challenges concern the management of large-scale
resources that depend on international cooperation, such as fresh water in
international basins or large marine ecosystems. Institutional diversity may be
as important as biological diversity for our long-term survival.
PMID- 10195887
TI - Digital logic gate using quantum-Dot cellular automata
AB - A functioning logic gate based on quantum-dot cellular automata is presented,
where digital data are encoded in the positions of only two electrons. The logic
gate consists of a cell, composed of four dots connected in a ring by tunnel
junctions, and two single-dot electrometers. The device is operated by applying
inputs to the gates of the cell. The logic AND and OR operations are verified
using the electrometer outputs. Theoretical simulations of the logic gate output
characteristics are in excellent agreement with experiment.
PMID- 10195888
TI - Remote triggering of waves in an electrochemical system
AB - In the potentiostatic electrochemical oxidation of formic acid on a platinum ring
electrode under bistable conditions, an appropriate perturbation at one location
of the ring can cause the emergence of a wave on the opposite side (remote
triggering). These findings can be rationalized in terms of the nonlocal coupling
function of the system and are theoretically reproduced by solution of the
corresponding reaction-migration equation.
PMID- 10195889
TI - Electrodeposited ceramic single crystals
AB - Single-crystal films are essential for devices because the intrinsic properties
of the material, rather than its grain boundaries, can be exploited. Cubic
bismuth oxide has the highest known oxide ion mobility, which makes it useful for
fuel cells and sensors, but it is normally only stable from 729 degrees to 825
degrees C. The material has not been previously observed at room temperature.
Single-crystal films of the high-temperature cubic polymorph of bismuth oxide
were epitaxially electrodeposited from an aqueous solution onto single-crystal
gold substrates. The 35.4 percent lattice mismatch was accommodated by forming
coincidence lattices in which the bismuth oxide film was rotated in relation to
the gold substrate. These results provide a method for producing other
nonequilibrium phases that cannot be accessed by traditional thermal processing.
PMID- 10195890
TI - The fermionic hanbury brown and twiss experiment
AB - A Hanbury Brown and Twiss experiment for a beam of electrons has been realized in
a two-dimensional electron gas in the quantum Hall regime. A metallic split gate
serves as a tunable beam splitter to partition the incident beam into transmitted
and reflected partial beams. In the nonequilibrium case the fluctuations in the
partial beams are shown to be fully anticorrelated, demonstrating that fermions
exclude each other. In equilibrium, the cross-correlation of current fluctuations
at two different contacts is also found to be negative and nonzero, provided that
a direct transmission exists between the contacts.
PMID- 10195891
TI - Hanbury brown and twiss-type experiment with electrons
AB - Fermion anti-bunching was directly observed by measuring the cross-covariance of
the current fluctuations of partitioned electrons. A quantum point contact was
used to inject single-mode electrons into a mesoscopic electron beam splitter
device. The beam splitter output currents showed negative cross-covariance,
indicating that the electrons arrived individually at the beam splitter and were
randomly partitioned into two output channels. As the relative time delay between
the outputs was changed, the observed ringing in the cross-covariance was
consistent with the bandwidths used to monitor the fluctuations. The result
demonstrates a fermion complement to the Hanbury Brown and Twiss experiment for
photons.
PMID- 10195892
TI - The robust australopithecine face: a morphogenetic perspective.
AB - The robust australopithecines were a side branch of human evolution. They share a
number of unique craniodental features that suggest their monophyletic origin.
However, virtually all of these traits appear to reflect a singular pattern of
nasomaxillary modeling derived from their unusual dental proportions. Therefore,
recent cladistic analyses have not resolved the phylogenetic history of these
early hominids. Efforts to increase cladistic resolution by defining traits at
greater levels of anatomical detail have instead introduced substantial phyletic
error.
PMID- 10195893
TI - Solar cycle variability, ozone, and climate
AB - Results from a global climate model including an interactive parameterization of
stratospheric chemistry show how upper stratospheric ozone changes may amplify
observed, 11-year solar cycle irradiance changes to affect climate. In the model,
circulation changes initially induced in the stratosphere subsequently penetrate
into the troposphere, demonstrating the importance of the dynamical coupling
between the stratosphere and troposphere. The model reproduces many observed 11
year oscillations, including the relatively long record of geopotential height
variations; hence, it implies that these oscillations are likely driven, at least
in part, by solar variability.
PMID- 10195894
TI - Positive and negative regulation of IkappaB kinase activity through IKKbeta
subunit phosphorylation.
AB - IkappaB [inhibitor of nuclear factor kappaB (NF-kappaB)] kinase (IKK)
phosphorylates IkappaB inhibitory proteins, causing their degradation and
activation of transcription factor NF-kappaB, a master activator of inflammatory
responses. IKK is composed of three subunits-IKKalpha and IKKbeta, which are
highly similar protein kinases, and IKKgamma, a regulatory subunit. In mammalian
cells, phosphorylation of two sites at the activation loop of IKKbeta was
essential for activation of IKK by tumor necrosis factor and interleukin-1.
Elimination of equivalent sites in IKKalpha, however, did not interfere with IKK
activation. Thus, IKKbeta, not IKKalpha, is the target for proinflammatory
stimuli. Once activated, IKKbeta autophosphorylated at a carboxyl-terminal serine
cluster. Such phosphorylation decreased IKK activity and may prevent prolonged
activation of the inflammatory response.
PMID- 10195895
TI - Limb and skin abnormalities in mice lacking IKKalpha.
AB - The gene encoding inhibitor of kappa B (IkappaB) kinase alpha (IKKalpha; also
called IKK1) was disrupted by gene targeting. IKKalpha-deficient mice died
perinatally. In IKKalpha-deficient fetuses, limb outgrowth was severely impaired
despite unaffected skeletal development. The epidermal cells in IKKalpha
deficient fetuses were highly proliferative with dysregulated epidermal
differentiation. In the basal layer, degradation of IkappaB and nuclear
localization of nuclear factor kappa B (NF-kappaB) were not observed. Thus,
IKKalpha is essential for NF-kappaB activation in the limb and skin during
embryogenesis. In contrast, there was no impairment of NF-kappaB activation
induced by either interleukin-1 or tumor necrosis factor-alpha in IKKalpha
deficient embryonic fibroblasts and thymocytes, indicating that IKKalpha is not
essential for cytokine-induced activation of NF-kappaB.
PMID- 10195896
TI - Abnormal morphogenesis but intact IKK activation in mice lacking the IKKalpha
subunit of IkappaB kinase.
AB - The oligomeric IkappaB kinase (IKK) is composed of three polypeptides: IKKalpha
and IKKbeta, the catalytic subunits, and IKKgamma, a regulatory subunit. IKKalpha
and IKKbeta are similar in structure and thought to have similar function
phosphorylation of the IkappaB inhibitors in response to proinflammatory stimuli.
Such phosphorylation leads to degradation of IkappaB and activation of nuclear
factor kappaB transcription factors. The physiological function of these protein
kinases was explored by analysis of IKKalpha-deficient mice. IKKalpha was not
required for activation of IKK and degradation of IkappaB by proinflammatory
stimuli. Instead, loss of IKKalpha interfered with multiple morphogenetic events,
including limb and skeletal patterning and proliferation and differentiation of
epidermal keratinocytes.
PMID- 10195897
TI - Severe liver degeneration in mice lacking the IkappaB kinase 2 gene.
AB - Phosphorylation of inhibitor of kappa B (IkappaB) proteins is an important step
in the activation of the transcription nuclear factor kappa B (NF-kappaB) and
requires two IkappaB kinases, IKK1 (IKKalpha) and IKK2 (IKKbeta). Mice that are
devoid of the IKK2 gene had extensive liver damage from apoptosis and died as
embryos, but these mice could be rescued by the inactivation of the gene encoding
tumor necrosis factor receptor 1. Mouse embryonic fibroblast cells that were
isolated from IKK2-/- embryos showed a marked reduction in tumor necrosis factor
alpha (TNF-alpha)- and interleukin-1alpha-induced NF-kappaB activity and an
enhanced apoptosis in response to TNF-alpha. IKK1 associated with NF-kappaB
essential modulator (IKKgamma/IKKAP1), another component of the IKK complex.
These results show that IKK2 is essential for mouse development and cannot be
substituted with IKK1.
PMID- 10195898
TI - Evolution of a protein fold in vitro.
AB - A "switch" mutant of the Arc repressor homodimer was constructed by interchanging
the sequence positions of a hydrophobic core residue, leucine 12, and an adjacent
surface polar residue, asparagine 11, in each strand of an intersubunit beta
sheet. The mutant protein adopts a fold in which each beta strand is replaced by
a right-handed helix and side chains in this region undergo significant
repacking. The observed structural changes allow the protein to maintain solvent
exposure of polar side chains and optimal burial of hydrophobic side chains.
These results suggest that new protein folds can evolve from existing folds
without drastic or large-scale mutagenesis.
PMID- 10195899
TI - The Pex16p homolog SSE1 and storage organelle formation in Arabidopsis seeds.
AB - Mature Arabidopsis seeds are enriched in storage proteins and lipids, but lack
starch. In the shrunken seed 1 (sse1) mutant, however, starch is favored over
proteins and lipids as the major storage compound. SSE1 has 26 percent identity
with Pex16p in Yarrowia lipolytica and complements pex16 mutants defective in the
formation of peroxisomes and the transportation of plasma membrane- and cell wall
associated proteins. In Arabidopsis maturing seeds, SSE1 is required for protein
and oil body biogenesis, both of which are endoplasmic reticulum-dependent.
Starch accumulation in sse1 suggests that starch formation is a default storage
deposition pathway.
PMID- 10195900
TI - Regulation of maternal behavior and offspring growth by paternally expressed
Peg3.
AB - Imprinted genes display parent-of-origin-dependent monoallelic expression that
apparently regulates complex mammalian traits, including growth and behavior. The
Peg3 gene is expressed in embryos and the adult brain from the paternal allele
only. A mutation in the Peg3 gene resulted in growth retardation, as well as a
striking impairment of maternal behavior that frequently resulted in death of the
offspring. This result may be partly due to defective neuronal connectivity, as
well as reduced oxytocin neurons in the hypothalamus, because mutant mothers were
deficient in milk ejection. This study provides further insights on the evolution
of epigenetic regulation of imprinted gene dosage in modulating mammalian growth
and behavior.
PMID- 10195901
TI - Self-similarity in the distribution and abundance of species
AB - If the fraction of species in area A that are also found in one-half of that area
is independent of A, the distribution of species is self-similar and a number of
observed patterns in ecology, including the widely cited species-area
relationship connecting species richness to censused area, follow. Self
similarity also leads to a species-abundance distribution, which deviates
considerably from the commonly assumed lognormal distribution and predicts
considerably more rare species than the latter. Because the abundance
distribution is derived under the condition of self-similarity, it may be widely
applicable beyond ecology.
PMID- 10195902
TI - NMDA receptor-mediated K+ efflux and neuronal apoptosis.
AB - Neuronal death induced by activating N-methyl-D-aspartate (NMDA) receptors has
been linked to Ca2+ and Na+ influx through associated channels. Whole-cell
recording from cultured mouse cortical neurons revealed a NMDA-evoked outward
current, INMDA-K, carried by K+ efflux at membrane potentials positive to -86
millivolts. Cortical neurons exposed to NMDA in medium containing reduced Na+ and
Ca2+ (as found in ischemic brain tissue) lost substantial intracellular K+ and
underwent apoptosis. Both K+ loss and apoptosis were attenuated by increasing
extracellular K+, even when voltage-gated Ca2+ channels were blocked. Thus NMDA
receptor-mediated K+ efflux may contribute to neuronal apoptosis after brain
ischemia.
PMID- 10195903
TI - Ca2+-induced apoptosis through calcineurin dephosphorylation of BAD.
AB - The Ca2+-activated protein phosphatase calcineurin induces apoptosis, but the
mechanism is unknown. Calcineurin was found to dephosphorylate BAD, a pro
apoptotic member of the Bcl-2 family, thus enhancing BAD heterodimerization with
Bcl-xL and promoting apoptosis. The Ca2+-induced dephosphorylation of BAD
correlated with its dissociation from 14-3-3 in the cytosol and translocation to
mitochondria where Bcl-xL resides. In hippocampal neurons, L-glutamate, an
inducer of Ca2+ influx and calcineurin activation, triggered mitochondrial
targeting of BAD and apoptosis, which were both suppressible by coexpression of a
dominant-inhibitory mutant of calcineurin or pharmacological inhibitors of this
phosphatase. Thus, a Ca2+-inducible mechanism for apoptosis induction operates by
regulating BAD phosphorylation and localization in cells.
PMID- 10195904
TI - In memoriam. Tribute to Werner Risau: December 18, 1953-December 13, 1998.
PMID- 10195905
TI - In memoriam. Professor George Joseph Popj'ak, MD, DSc, FRS May 5, 1914-December
30, 1998.
PMID- 10195906
TI - Cholesterol and lipoprotein metabolism in aging: reversal of hypercholesterolemia
by growth hormone treatment in old rats.
AB - Plasma cholesterol levels increase with age, as does the incidence of coronary
heart disease. The mechanisms responsible for the age-related
hypercholesterolemia are not well understood. An interesting hypothesis suggests
that the relative deficiency in growth hormone (GH), which occurs with aging,
contributes to the development of the age-related hypercholesterolemia, because
GH has beneficial effects on cholesterol metabolism. In the present work, we
tested this hypothesis by the administration of GH to normal rats of varying
ages. Plasma lipids and hepatic cholesterol metabolism were characterized in 2-,
12-, and 18-month-old male Sprague-Dawley rats. In 2-month-old rats, GH
specifically stimulated the hepatic low density lipoprotein (LDL) receptor
expression in a dose-dependent way, both at the protein level and at the mRNA
level. Concomitantly, plasma cholesterol increased by approximately 30% within
the large high density lipoprotein and LDL fractions. In 12-month-old animals,
cholesterol 7alpha-hydroxylase (C7alphaOH) activity was reduced, whereas hepatic
LDL receptors and plasma total cholesterol were unchanged. GH treatment (1 mg. kg
1. d-1) normalized the activity of C7alphaOH and had effects on plasma
cholesterol and LDL receptors similar to those seen in 2-month-old animals. In 18
month-old rats, plasma cholesterol was increased 2-fold, whereas hepatic LDL
receptor expression and C7alphaOH activity were similar to those of the 12-month
old animals. Infusion of GH to 18-month-old rats had similar effects on hepatic
C7alphaOH and LDL receptors as seen in 12-month-old rats. However, GH treatment
strongly reduced the hypercholesterolemia in 18-month-old animals. We conclude
that the age-dependent increase of plasma cholesterol in rats can be reversed by
the administration of GH, presumably through the pleiotropic effects of this
hormone on lipoprotein metabolism.
PMID- 10195907
TI - 17 beta-estradiol reduces glycoxidative damage in the artery wall.
AB - Glycoxidative damage in the vasculature has been linked to atherosclerotic
cardiovascular disease. Estrogens protect against the development and progression
of atherosclerosis. Because estrogens are potent antioxidants that also effect
glucose metabolism, part of their protection against atherosclerosis could be
through attenuation of glycoxidative damage in the vascular wall. In this study,
we tested the hypothesis that chronic estradiol administration is associated with
decreased levels of glycoxidative damage in arterial walls. We harvested and
examined iliac arteries from ovariectomized, 8-month-old rats that had been
implanted for 6 months with 1 of the following subcutaneous hormone pellets: low
estradiol (2.5 mg estradiol), high estradiol (25 mg estradiol), P4 (200 mg
progesterone), low estradiol and P4, placebo (no hormone), or control (no
implant). Using pentosidine as a biomarker of glycoxidative damage, we found that
all vessels from rats receiving estradiol (low estradiol, high estradiol, and low
estradiol+P4) exhibited a 50% reduction in glycoxidative damage compared with P4,
placebo, and control vessels (P<0.05). Consistent with this finding, we observed
that estradiol-treated rats had a 30% decrease in tissue levels of
hydroperoxides, a marker of oxidative stress. Finally, estradiol-treated rats had
a small, but significant, decrease in plasma glucose levels (P<0.01). In summary,
we report the novel finding that chronic estrogen administration is associated
with significant decreases in glycoxidative damage and oxidative stress in the
arterial wall. It seems likely that these actions may constitute a mechanism by
which estrogen attenuates the progression of atherosclerosis.
PMID- 10195908
TI - Ultrastructure of early lipid accumulation in ApoE-deficient mice.
AB - Apolipoprotein (apo) E-deficient mice develop severe hypercholesterolemia and
have lesions that progress from fatty streaks to fibrous plaques distributed in
lesion-prone areas throughout the aorta. Lesions develop in apoE-deficient mice
on a regular chow diet and will occur faster on a diet higher in cholesterol.
Examination of the aortas from these mice on a chow diet by high-resolution,
freeze-etch electron microscopy demonstrated lipid retention in the intima by 3
weeks of age. Lipid was retained in the matrix as individual particles between 33
and 48 nm in diameter, aligned along the collagen fibrils and in aggregates
consisting of lipid particles with average diameters of 33 and 68 nm. Larger
particles seemed to have formed from fusion of smaller particles. Lipid retention
was more widespread in 5- and 9-week-old mice. Monocyte attachment to endothelial
cells was observed by electron microscopy at 5 weeks of age. The appearance of
the intimal lipid was similar to that previously described in rabbit models and
suggests that lipid interaction with matrix filaments and subsequent aggregation
of lipid particles are critical first steps in the process of foam cell
formation.
PMID- 10195909
TI - Modified LDL-mediated increases in endothelial layer permeability are attenuated
with 17 beta-estradiol.
AB - -Current research suggests that estrogen may have primary effects on the artery
wall. To investigate the mechanisms of female sex hormone actions in the artery
wall, we used an isolated, perfused, rat carotid artery model to examine the
effects of estradiol on the rates of accumulation of normal (N-LDL) and minimally
modified (MM-LDL) low density lipoprotein in ovariectomized rats. N-LDL, MM-LDL,
and oxidized LDL (OX-LDL) were fluorescently labeled and perfused into individual
arteries. The rate of LDL accumulation was measured by quantitative fluorescence
microscopy before and after treatment with estradiol (1 nmol/L, 272 pg/mL).
Estradiol had no effect on the rate of N-LDL accumulation (45+/-12 versus 48+/-15
ng cholesterol per cm2 per h). However, estradiol significantly decreased the
rate of MM-LDL (240+/-48 versus 160+/-48 ng cholesterol per cm2 per h; P<0.05)
and OX-LDL (191+/-53 versus 112+/-36 ng cholesterol per cm2 per h; P<0.05)
accumulation. Further experiments showed that perfusion of unlabeled MM-LDL (100
microgram/mL) increased endothelial layer permeability when the rate of
accumulation of a water-soluble, fluorescently labeled, reference molecule (64
000-molecular weight dextran) was determined before and after perfusion of MM-LDL
(319+/-96 versus 510+/-191 ng per cm2 per h, n=6 arteries; P<0.05). Estradiol
prevented the expected increase in the rate of dextran accumulation when perfused
with MM-LDL (control, 415+/-49 ng per cm2 per h and MM-LDL+estradiol, 415+/-160
ng per cm2 per h). Our studies show that estradiol prevents compromise of the
endothelial barrier mediated by MM-LDL and attenuates accumulation of MM-LDL in
the artery wall.
PMID- 10195910
TI - Polymorphisms of the tissue factor pathway inhibitor (TFPI) gene in patients with
acute coronary syndromes and in healthy subjects : impact of the V264M
substitution on plasma levels of TFPI.
AB - -Mutations of the gene encoding tissue factor pathway inhibitor (TFPI), an
inhibitor of TF-induced activation of the coagulation cascade, were screened for
in 130 patients and 142 healthy controls to determine whether these variants
contribute to acute coronary syndromes or modify plasma TFPI levels. The
following 3 new polymorphisms were identified: 384T-->C in exon IV, which does
not change the corresponding amino acid (tyrosine 57); -33C-->T in intron 7 (the
T/T, C/T, and C/C genotypes were found in approximately 50%, 40%, and 10% of
subjects in both groups); and 874G-->A in exon IX (GTG-->ATG), which predicts a
valine to methionine change (V264M) in the carboxy-terminus tail of TFPI. The
V264M polymorphism was found in 9.2% of the cases and 4.9% of the controls; the
associated odds ratio (OR) for acute coronary syndromes was 2.0 (95% confidence
interval [CI], 0.7 to 5.1). The OR increased to 3.6 (95% CI, 0.8 to 15.7) and 3.2
(95% CI, 0.9 to 11.8) in nonsmokers and patients without other risk factors,
respectively. The possible link between the V264M polymorphism and coronary heart
disease was checked in a large case-control study of myocardial infarction (Etude
Cas-Temoins de l'Infarctus du Myocarde [the ECTIM Study]). The results showed no
link between the V264M polymorphism and coronary syndromes. Interestingly,
however, 5 patients heterozygous for the V264M polymorphism had significantly
lower plasma TFPI levels than did 13 patients with the most common genotype.
Although our present results do not support an association between TFPI
polymorphisms and acute coronary syndromes, the possibility that 1 of them,
especially the exon IX polymorphism, is associated with subtypes of myocardial
infarction or to evolutive particularities that were not assessed in this study,
cannot be excluded and is currently being evaluated.
PMID- 10195911
TI - Evidence of hypoxic areas within the arterial wall in vivo.
AB - The anoxemia theory of atherosclerosis states that an imbalance between the
demand and supply of oxygen in the arterial wall is a key factor for the
development of atherosclerotic lesions. Direct in vitro and in situ measurements
have shown that PO2 is decreased in the more deeply situated parts of the media,
but the degree of hypoxia in vivo or the distribution of hypoxia along the
arterial tree is not known. For this reason, we have developed a method for the
detection of hypoxia in the arterial wall in vivo by using a hypoxia marker, 7
(4'-(2-nitroimidazol-1-yl)-butyl)-theophylline, that may be visualized by
immunofluorescence. In the present study, we have used this method in rabbits
with experimentally induced atherosclerosis. Our results indicate that zones of
hypoxia occur at depth in the atherosclerotic plaque. The mechanism was probably
an impaired oxygen diffusion capacity due to the thickness of the lesion,
together with high oxygen consumption by the foam cells. Thus, we have for the
first time demonstrated that hypoxia actually does exist in the arterial wall in
vivo, lending support to the anoxemia theory of atherosclerosis.
PMID- 10195912
TI - AJvW-2, an anti-vWF monoclonal antibody, inhibits enhanced platelet aggregation
induced by high shear stress in platelet-rich plasma from patients with acute
coronary syndromes.
AB - The platelet aggregation that is dependent on von Willebrand factor (vWF) is
important in the thrombogenesis that occurs under conditions of high shear
stress, eg, during acute coronary syndromes (ACSs). A monoclonal antibody, AJvW
2, directed against the A1 domain of human vWF specifically blocks the
interaction between plasma vWF and platelet glycoprotein (GP) Ib. To evaluate the
association between the vWF-GPIb interaction and the enhanced shear-induced
platelet aggregation (SIPA) observed in ACSs, we tested the effect of this
antibody on platelet aggregation. Platelet-rich plasma was prepared from the
citrated blood of 12 patients with unstable angina (UAP) and 20 patients with
acute myocardial infarction (AMI) who were admitted within 3 hours of the onset
of cardiac symptoms and from 18 controls. We observed the following: (1) 1.7-fold
higher plasma levels of vWF and ristocetin cofactor activity in UAP patients and
(2) 2.8-fold higher levels in the AMI group than in controls. Using a cone-and
plate viscometer, we measured the mean value of SIPA under high-shear conditions
(108 dyne/cm2) and found them to be 1.3-fold higher in the UAP group and 2.0-fold
higher in the AMI group than in controls. The high SIPA in all groups was
completely inhibited by 10 microgram/mL AJvW-2. Under low-shear conditions (12
dyne/cm2), platelet aggregation was increased only in the AMI group, but this was
unaffected by AJvW-2. We observed a significant correlation in both ACS groups
between high SIPA and the plasma vWF level or vWF larger multimers. These
findings suggest that the vWF-GPIb interaction is important in coronary occlusion
and that inhibition of this interaction (with the use of AJvW-2) may prevent
further events in the coronary arteries.
PMID- 10195913
TI - Individual propensity for arterial thrombosis.
AB - Arterial thrombophilia independent of vascular pathology has not been previously
defined either experimentally or epidemiologically. To address the existence of
an individual propensity to arterial thrombosis, we exploited a previously
developed procedure entailing traumatic (crush) injury of paired porcine carotid
arteries for generating platelet-rich thrombi. Porcine carotid arteries were
injured bilaterally by serial hemostat crushes. Thrombus generation was monitored
by local accumulation of autologous 111In-labeled platelets and Doppler blood
flow. Within this cohort of animals of similar age and size, the lowest to the
highest responders in thrombus mass spanned a 7-fold range, showing no
correlation with shear, platelet or leukocyte count, or plasma concentrations of
fibrinogen or von Willebrand factor. However, there was strong intra-individual
correlation (r2=0.80; P<0.001) of thrombus deposition between carotid artery
pairs. The wide variation in thrombotic response to a standardized stimulus, not
accounted for by shear stress or typical hematological variables, appears to be
an intrinsic propensity of the individual. The experimental system for thrombus
generation is sufficiently quantitative for assessment of variables determining
this propensity.
PMID- 10195914
TI - Fibrinogen: a possible link between alcohol consumption and cardiovascular
disease? DESIR Study Group.
AB - The relation between alcohol consumption and fibrinogen concentration was
evaluated in a French population to investigate whether fibrinogen could explain
part of the relation between alcohol consumption and cardiovascular disease.
Cross-sectional data on self-reported alcohol consumption and fibrinogen,
measured by the immunonephelometric method, of 4967 men and women aged 30 to 64
years were used. These subjects were volunteers for a free health checkup in the
western central part of France from 1994 to 1996 and participated in the DESIR
Study (Data from an Epidemiological Study on the Insulin Resistance syndrome).
Alcohol consumption was strongly associated with fibrinogen concentration, with
higher concentrations in those who were nondrinkers or who drank >60 g of alcohol
per day. This U-shaped association was stronger among men than women. Consumption
of wine and spirits was associated with fibrinogen, whereas consumption of beer
or cider was not. Furthermore, smoking was positively associated with fibrinogen
concentration, and in men the difference between nondrinkers and drinkers with
the lowest fibrinogen level was higher in nonsmokers and ex-smokers than in
current smokers. We conclude that moderate drinking may lower fibrinogen
concentration. If fibrinogen is a causal risk factor for cardiovascular disease,
it may be 1 of the variables that explain the protective effect of moderate
alcohol consumption on cardiovascular disease.
PMID- 10195915
TI - Hormone replacement therapy, inflammation, and hemostasis in elderly women.
AB - Lipid-lowering by postmenopausal hormone therapy (HRT) explains only partly the
assumed coronary risk reduction associated with therapy. To explore other
possible mechanisms, we studied associations of HRT use with inflammation and
hemostasis risk markers in women >/=65 years of age. Subjects were selected from
3393 participants in the fourth year examination of the Cardiovascular Health
Study, an observational study of vascular disease risk factors. After excluding
women with vascular disease, we compared levels of inflammation and hemostasis
variables in the 230 women using unopposed estrogen and 60 using
estrogen/progestin, with those of 196 nonusers selected as controls. Compared
with nonusers, unopposed estrogen use was associated with 59% higher mean C
reactive protein (P<0.001), but with modestly lower levels of other inflammation
indicators, fibrinogen, and alpha-1 acid glycoprotein (P<0.001). Factor VIIc was
16% higher among estrogen users (P<0.001), but this was not associated with
higher thrombin production (prothrombin fragment 1-2), or increased fibrin
breakdown (D-dimer). Concentration of plasminogen activator inhibitor-1 was 50%
lower in both using groups (P<0.001) compared with nonusers, and this was
associated with higher plasmin-antiplasmin complex: 8% higher in estrogen and 18%
higher in estrogen/progestin users (P<0. 05). Relationships between the markers
and hormone use were less pronounced in estrogen/progestin users, with no
association for C-reactive protein except in women in upper 2 tertiles of body
mass index (P for interaction, 0.02). The direction and strength of the
associations of HRT use with inflammation markers differed depending on the
protein, so it is not clear whether HRT confers coronary risk reduction through
an inflammation-sensitive mechanism. Associations with hemostasis markers
indicated no association with evidence of procoagulation and a possible
association with increased fibrinolytic activity.
PMID- 10195916
TI - The role of alpha and beta platelet-derived growth factor receptor in the
vascular response to injury in nonhuman primates.
AB - Restenosis remains a significant clinical problem associated with mechanical
interventional procedures for arterial revascularization or repair, including
coronary angioplasty and stenting. Studies with rodents have established that
platelet-derived growth factor (PDGF), a potent chemotactic and mitogenic agent
for vascular smooth muscle cells, is a key mediator of lesion formation after
vascular injury. To further explore this hypothesis in a more clinically relevant
model, neutralizing monoclonal antibodies (mAbs) were used to examine the effect
of selective inhibition of alpha or beta PDGF receptor (PDGFR) on neointima
formation in nonhuman primates. Carotid arteries were injured by surgical
endarterectomy and femoral arteries by balloon catheter dilatation.
Immunostaining revealed that both injuries induced cell proliferation and the
upregulation of beta PDGFR but not alpha PDGFR. By 7 days after injury, beta
PDGFR staining was limited to the luminal region of the media, the small areas of
neointima, and the adventitia. Nearly all bromodeoxyuridine-positive cells were
found in these regions as well. After 30 days, a concentric neointima that
stained strongly for beta PDGFR had formed in the carotid and femoral arteries.
Treatment of baboons with anti-beta PDGFR mAb 2A1E2 for 6 days after injury
reduced the carotid artery and femoral artery lesion sizes by 37% (P<0.05) and
48% (P<0.005), respectively, when measured at 30 days. Under the same conditions,
treatment with anti-alpha PDGFR mAb 2H7C5 had no effect. These findings suggest
that PDGF mediates neointima formation through the beta PDGFR, and that
antagonism of this pathway may be a promising therapeutic strategy for reducing
clinical restenosis.
PMID- 10195917
TI - High-density lipoproteins differentially modulate cytokine-induced expression of
E-selectin and cyclooxygenase-2.
AB - Atherogenesis is a multifactorial chronic inflammatory disease in which low
plasma levels of HDLs are a strong predictor of the condition. Although the
mechanism of protection by HDLs is not precisely known, HDLs have been shown to
influence many of the events involved in the development of atherosclerosis.
Previously we have shown that HDLs inhibited the cytokine-induced expression of
adhesion molecules (E-selectin, VCAM-1, and ICAM-1) by endothelial cells (ECs).
As the complete transcriptional regulation of all 3 genes requires the NF-kappaB
family of transcription factors, we examined the effect of HDLs on activation of
NF-kappaB. We also investigated the effect of HDLs on 2 other cytokine-induced
genes, granulocyte-macrophage colony-stimulating factor (GM-CSF) and
cyclooxygenase (Cox-2; prostaglandin H2 synthase, EC 0.1.14.99.1). E-selectin
expression in response to tumor necrosis factor-alpha (TNFalpha) was, as
expected, inhibited in ECs that had been preincubated with HDLs. However, the
level of secretion of GM-CSF in the same cultures was no different from control.
In a similar manner, although HDLs had no effect on steady-state mRNA levels of
GM-CSF, the levels of E-selectin were significantly inhibited by HDLs. In
transient cotransfection experiments we found that HDLs inhibited the cytokine
induced expression of a reporter gene driven by the E-selectin proximal promoter
(-383 to 80) but had no effect on the expression of a reporter gene driven under
the control of the proximal promoter of GM-CSF (-627 to 28). As would be
predicted from this differential response, HDLs did not influence the nuclear
translocation or DNA binding of NF-kappaB, or alter the kinetics of degradation
and resynthesis of the inhibitory protein IkappaBalpha. We found that HDLs
synergized with cytokine to enhance the expression of Cox-2 and induce the
synthesis of its main EC product, prostacyclin (PGI2), a potent inhibitor of
platelet and leukocyte functions. In conclusion, HDL induces an antiinflammatory
phenotype in cytokine-induced ECs, synergizing with cytokine to induce elevation
of Cox-2 in addition to inhibiting adhesion molecule expression. Our studies show
that these differential effects are mediated in a manner that is likely to be
independent of NF-kappaB per se.
PMID- 10195918
TI - Dietary restriction of saturated fat and cholesterol decreases HDL ApoA-I
secretion.
AB - We examined the mechanisms responsible for the decrease in HDL cholesterol (HDL
C) levels after the consumption of a diet low in total fat, saturated fat, and
cholesterol. Twenty-one subjects with a mean age of 58+/-12 years were placed on
a baseline isocaloric diet (15% protein, 49% carbohydrate, 36% fat, and 150
mg/1000 kcals of cholesterol) and then switched to an NCEP Step 2 diet (15%
protein, 60% carbohydrate, 25% fat, and 45 mg/1000 kcals of cholesterol). After 6
or 24 weeks on each diet, subjects received a 15-hour primed-constant infusion of
[5,5,5-2H3]-L-leucine. HDL apoA-I and apoA-II tracer curves were determined by
gas chromatography-mass spectrometry and fitted to a monoexponential equation.
Compared with the baseline diet, consumption of the Step 2 diet lowered HDL-C
mean levels by 15% (1.03+/-0.23 to 0.88+/-0.16 mmol/L, P<0.001), apoA-I by 12%
(1.25+/-0.15 to 1.10+/-0.13 g/L, P<0. 001) and the TC/HDL-C ratio by 5% (0.145+/
0.04 to 0.137+/-0.03). No significant changes were observed in apoA-II levels and
HDL particle size with diet. HDL apoA-I fractional catabolic rate did not change
(0.219+/-0.052 to 0.220+/-0.043 pools/day, P=0.91) but HDL apoA-I secretion rate
decreased by 8% (12.26+/-3.07 to 10.84+/-2.11 mg. kg-1. day-1, P=0.03) during
consumption of the Step 2 diet. There was no effect of diet on apoA-II fractional
catabolic rate or secretion rate. Our results indicate that the decrease in HDL-C
and apoA-I levels during the isocaloric consumption of a Step 2 diet paralleled
the reductions in apoA-I secretion rate.
PMID- 10195919
TI - Uptake of 13-hydroperoxylinoleic acid by cultured cells.
AB - Oxidized free fatty acids have profound effects on cultured cells. However,
little is known about whether these effects depend on their uptake and metabolism
by cells or primarily involve their interaction with cell-surface components. We
determined the uptake and metabolism of unoxidized (linoleic or oleic acid) and
oxidized linoleic acid (13-hydroperoxyoctadecadienoic acid, 13-HPODE) by
endothelial cells, smooth muscle cells, and macrophages. We show that 13-HPODE is
poorly taken up by cells. The levels of uptake were dependent on the cell type
but were independent of the expression of CD36. 13-HPODE was also poorly used by
microsomal lysophosphatidylcholine acyltransferase that is involved in the
formation of phosphatidylcholine. Based on these results, we suggest that most of
the biological effects of 13-HPODE and other oxidized free fatty acids on cells
might involve a direct interaction with cell-surface components. Alternatively,
very small amounts of oxidized free fatty acids that enter the cell may have
effects, analogous to those of hormones or prostanoids.
PMID- 10195920
TI - A new promoter polymorphism in the gene of lipopolysaccharide receptor CD14 is
associated with expired myocardial infarction in patients with low
atherosclerotic risk profile.
AB - Recent findings suggest that inflammation plays a role in atherosclerosis and its
acute complications. Cellular response in infections with Gram-negative bacteria
is mediated by bacterial lipopolysaccharide (LPS), which activates monocytes to
expression of cytokines, growth factors, and procoagulatory factors via LPS
receptor CD14. Endothelial cells and smooth muscle cells are stimulated by a
complex of LPS and soluble CD14. In this study, LPS receptor CD14 was analyzed to
find genetic variants and check them for an association with coronary artery
disease or myocardial infarction (MI). When screening the CD14 gene by single
strand conformation polymorphism analysis, a promoter polymorphism was detected
and confirmed as a T-to-C exchange at position -159. We determined the genotypes
of 2228 men who had undergone coronary angiography for diagnostic purposes.
Within the total study group there was no significant association of either
genotype with MI or coronary artery disease. However, in a subgroup with low
coronary risk (normotensive nonsmokers), a relative risk for MI in probands
homozygous for the T allele could be evaluated (OR, 1.6; 95% CI, 1.0 to 2.4;
P<0.05). The association was even stronger in low-risk patients older than 62
years (OR, 3.8; 95% CI, 1.6 to 9.0; P<0.01). In conclusion, we describe a new
CD14 promoter polymorphism that is associated with MI, especially in older
patients with a low atherosclerotic risk profile.
PMID- 10195921
TI - ApoB100 secretion from HepG2 cells is decreased by the ACAT inhibitor CI-1011: an
effect associated with enhanced intracellular degradation of ApoB.
AB - The concept that hepatic cholesteryl ester (CE) mass and the rate of cholesterol
esterification regulate hepatocyte assembly and secretion of apoB-containing
lipoproteins remains controversial. The present study was carried out in HepG2
cells to correlate the rate of cholesterol esterification and CE mass with apoB
secretion by CI-1011, an acyl CoA:cholesterol acyltransferase (ACAT) inhibitor
that is known to decrease apoB secretion, in vivo, in miniature pigs. HepG2 cells
were incubated with CI-1011 (10 nmol/L, 1 micromol/L, and 10 micromol/L) for 24
hours. ApoB secretion into media was decreased by 25%, 27%, and 43%, respectively
(P<0.0012). CI-1011 (10 micromol/L) inhibited HepG2 cell ACAT activity by 79%
(P<0.002) and cellular CE mass by 32% (P<0.05). In contrast, another ACAT
inhibitor, DuP 128 (10 micromol/L), decreased cellular ACAT activity and CE mass
by 85% (P<0.002) and 42% (P=0.01), respectively, but had no effect on apoB
secretion into media. To characterize the reduction in apoB secretion by CI-1011,
pulse-chase experiments were performed and analyzed by multicompartmental
modelling using SAAM II. CI-1011 did not affect the synthesis of apoB or albumin.
However, apoB secretion into the media was decreased by 42% (P=0.019).
Intracellular apoB degradation increased proportionately (P=0.019). The secretion
of albumin and cellular reuptake of labeled lipoproteins were unchanged. CI-1011
and DuP 128 did not affect apoB mRNA concentrations. These results show that CI
1011 decreases apoB secretion by a mechanism that involves an enhanced
intracellular degradation of apoB. This study demonstrates that ACAT inhibitors
can exert differential effects on apoB secretion from HepG2 cells that do not
reflect their efficacy in inhibiting cholesterol esterification.
PMID- 10195922
TI - A bioluminescence method for the mapping of local ATP concentrations within the
arterial wall, with potential to assess the in vivo situation.
AB - According to the anoxemia theory of atherosclerosis, an imbalance between the
demand for and supply of oxygen and nutrients in the arterial wall is a key
factor in atherogenesis. However, the energy metabolic state of the arterial
tissue in vivo is largely unknown. We applied a bioluminescence method, metabolic
imaging, to study local ATP concentrations in cryosections of normal pig and
atherosclerotic and normal rabbit aorta. Some vessels were subjected to energy
metabolic restrictions by incubation at different oxygen and glucose
concentrations and others were rapidly frozen in liquid nitrogen to reflect the
in vivo situation. Local ATP concentrations and the ATP distribution at a
microscale was dependent on oxygen as well as glucose concentrations during
incubation. ATP depletion was seen in the mid media of pig aorta in all
incubations, but only at low oxygen concentration without glucose in the media of
the thinner rabbit aorta. ATP-depleted zones were seen deep in pig media (>750
microm from the lumen) and in rabbit plaques (>300 micrometer+ from the lumen)
even at high oxygen (pig 75% O2 and rabbit 21% O2) and glucose concentrations
(5.6 mmol/L glucose). This observation probably illustrates an insufficient
diffusion of glucose, which highlights the importance of studying the conditions
for diffusion not only of oxygen but also of other metabolites in the arterial
wall. In rapidly frozen vessels the medial ATP concentration was shown to be 0.6
to 0.8 micromol/g wet weight (both pig and rabbit aorta) and in pig aorta a
gradient could be seen indicating higher ATP concentrations at the lumenal side.
We propose that metabolic imaging, as applied to snap-frozen tissue, may be used
to assess the energy metabolic situation in the arterial wall in vivo. The
spatial resolution allows the detection of local variations within the arterial
tree. However, steep concentration gradients (eg, near the border of the tissue)
will be underestimated. The method may be extended to include determinations of
glucose and lactate concentrations and will be used in parallel with an
established method to assess hypoxia in the arterial wall in vivo.
PMID- 10195923
TI - Farnesol blocks the L-type Ca2+ channel by targeting the alpha 1C subunit.
AB - We recently demonstrated that farnesol, a 15-carbon isoprenoid, blocks L-type
Ca2+ channels in vascular smooth muscle cells. To elucidate farnesol's mechanism
of action, we performed whole-cell and perforated-patch clamp experiments in rat
aortic A7r5 cells and in Chinese hamster ovary (CHO) C9 cells expressing smooth
muscle Ca2+ channel alpha 1C subunits. Farnesol dose-dependently and voltage
independently inhibited Ba2+ currents in both A7r5 and CHOC9 cells, with similar
half-maximal inhibitions at 2.6 and 4.3 micromol/L, [corrected] respectively
(P=NS). In both cell lines, current inhibition by farnesol was prominent over the
whole voltage range without changes in the current-voltage relationship peaks.
Neither intracellular infusion of the stable GDP analogue guanosine-5'-O-(2
thiodiphosphate) (100 micromol/L) [corrected] via the patch pipette nor strong
conditioning membrane depolarization prevented the inhibitory effect of farnesol,
which indicates G protein-independent inhibition of Ca2+ channels. In an analysis
of the steady-state inactivation curve for voltage dependence, farnesol induced a
significant, negative shift ( approximately 10 mV) of the potential causing 50%
channel inactivation in both cell lines (P<0. 001). In contrast, the steepness
factor characterizing the voltage sensitivity of the channels was unaffected.
Unlike pharmacological Ca2+ channel blockers, farnesol blocked Ca2+ currents in
the resting state: initial block was 63+/-8% in A7r5 cells and 50+/-9% in CHOC9
cells at a holding potential of -80 mV. We then gave 500 mg/kg body weight
farnesol by gavage to Sabra hypertensive and normotensive rats and found that
farnesol reduced blood pressure significantly in the hypertensive strain for at
least 48 hours. We conclude that farnesol may represent an endogenous smooth
muscle L-type Ca2+ channel antagonist. Because farnesol is active in cells
expressing only the pore-forming alpha1 subunit, the data further suggest that
this subunit represents the molecular target for farnesol binding and principal
action. Finally, farnesol has a blood pressure-lowering action that may be
relevant in vivo.
PMID- 10195924
TI - Increased plasma 7 beta-hydroxycholesterol concentrations in a population with a
high risk for cardiovascular disease.
AB - The mortality in coronary heart disease among 50- to 54-year-old men is 4 times
higher in Lithuania than in Sweden. It was recently suggested that traditional
risk factors could not explain this mortality difference. LDL of Lithuanian men
showed, however, a lower resistance to oxidation than that of Swedish men. In
addition, the plasma concentration of gamma-tocopherol, lycopene, and beta
carotene were lower in Lithuanian men. In the present investigation, we
determined plasma oxysterols in men from Lithuania and Sweden and found that the
plasma concentration of 7 beta-hydroxycholesterol was higher in Lithuanian men,
12+/-5 versus 9+/-8 (SD) ng/mL (P=0.0011). This oxysterol is a cholesterol
autoxidation product and there is no indication that it should have an enzymatic
origin. Mean LDL oxidation lag time was shorter in Lithuanian men (75+/-14 versus
90+/-13 minutes, P<0.0001) and the concentration of LDL linoleic acid was lower
(249+/-56 versus 292+/-54 microgram/mg of LDL protein, P<0.0001). Lipid corrected
gamma-tocopherol was 0.07+/-0.02 mg/mL in Vilnius men and 0.12+/-0. 04 mg/mL
(P<0.0001) in Linkoping men. There was a negative correlation between the
concentration of 7 beta-hydroxycholesterol and lag time (R=-0.31, P=0.0023). It
is suggested that the higher 7 beta-hydroxycholesterol concentration in
Lithuanian men is an indication of an increased in vivo lipid peroxidation.
PMID- 10195925
TI - C-reactive protein in healthy subjects: associations with obesity, insulin
resistance, and endothelial dysfunction: a potential role for cytokines
originating from adipose tissue?
AB - C-reactive protein, a hepatic acute phase protein largely regulated by
circulating levels of interleukin-6, predicts coronary heart disease incidence in
healthy subjects. We have shown that subcutaneous adipose tissue secretes
interleukin-6 in vivo. In this study we have sought associations of levels of C
reactive protein and interleukin-6 with measures of obesity and of chronic
infection as their putative determinants. We have also related levels of C
reactive protein and interleukin-6 to markers of the insulin resistance syndrome
and of endothelial dysfunction. We performed a cross-sectional study in 107
nondiabetic subjects: (1) Levels of C-reactive protein, and concentrations of the
proinflammatory cytokines interleukin-6 and tumor necrosis factor-alpha, were
related to all measures of obesity, but titers of antibodies to Helicobacter
pylori were only weakly and those of Chlamydia pneumoniae and cytomegalovirus
were not significantly correlated with levels of these molecules. Levels of C
reactive protein were significantly related to those of interleukin-6 (r=0.37,
P<0.0005) and tumor necrosis factor-alpha (r=0.46, P<0.0001). (2) Concentrations
of C-reactive protein were related to insulin resistance as calculated from the
homoeostasis model assessment model, blood pressure, HDL, and triglyceride, and
to markers of endothelial dysfunction (plasma levels of von Willebrand factor,
tissue plasminogen activator, and cellular fibronectin). A mean standard
deviation score of levels of acute phase markers correlated closely with a
similar score of insulin resistance syndrome variables (r=0.59, P<0.00005), this
relationship being weakened only marginally by removing measures of obesity from
the insulin resistance score (r=0.53, P<0.00005). These data suggest that adipose
tissue is an important determinant of a low level, chronic inflammatory state as
reflected by levels of interleukin-6, tumor necrosis factor-alpha, and C-reactive
protein, and that infection with H pylori, C pneumoniae, and cytomegalovirus is
not. Moreover, our data support the concept that such a low-level, chronic
inflammatory state may induce insulin resistance and endothelial dysfunction and
thus link the latter phenomena with obesity and cardiovascular disease.
PMID- 10195926
TI - Acute effects of intravenous infusion of ApoA1/phosphatidylcholine discs on
plasma lipoproteins in humans.
AB - To investigate the metabolism of nascent HDLs, apoA1/phosphatidylcholine
(apoA1/PC) discs were infused IV over 4 hours into 7 healthy men. Plasma total
apoA1 and phospholipid (PL) concentrations increased during the infusions. The
rise in plasma apoA1 was greatest in small prebeta-migrating particles not
present in the infusate. Total HDL unesterified cholesterol (UC) also increased
simultaneously. After stopping the infusion, the concentrations of apoA1, PL, HDL
UC, and small prebeta HDLs decreased, whereas those of HDL cholesteryl ester (CE)
and large alpha-migrating apoA1 containing HDLs increased. ApoB-containing
lipoproteins became enriched in CEs. Addition of apoA1/PC discs to whole blood at
37 degrees C in vitro also generated small prebeta HDLs, but did not augment the
transfer of UC from erythrocytes to plasma. We conclude that the disc infusions
increased the intravascular production of small prebeta HDLs in vivo, and that
this was associated with an increase in the efflux and esterification of UC
derived from fixed tissues. The extent to which the increase in tissue
cholesterol efflux was dependent on that in prebeta HDL production could not be
determined. Infusion of discs also reduced the plasma apoB and apoA2
concentrations, and increased plasma triglycerides and apoC3. Thus, nascent HDL
secretion may have a significant impact on prebeta HDL production, reverse
cholesterol transport and lipoprotein metabolism in humans.
PMID- 10195927
TI - Effect of Lp(a) on the early functional and structural changes of
atherosclerosis.
AB - Epidemiologic studies have shown a significant relationship between elevated
plasma levels of Lp(a) and increased risk of cardiovascular events; however, the
mechanisms by which elevated Lp(a) levels produce this increased risk are not
known. To test the hypothesis that high Lp(a) levels might contribute to the
development of subclinical atherosclerosis, we examined the influence of Lp(a)
levels on early functional and structural atherosclerotic vascular changes. Flow
mediated (endothelium-dependent) and nitrate-mediated (smooth muscle-dependent)
arterial dilations were measured by high-resolution ultrasound in 241 normal
healthy subjects (aged 15 to 69 years; 116 men). In addition, carotid artery
intima-media thickness was measured by ultrasound in 71 subjects. Plasma Lp(a)
was measured using a 2-sided immunoradiometric assay (cohort median, 10 mg/dL;
interquartile range, 3.9 to 24.4 mg/dL). In these subjects, there were no
significant relationships between Lp(a) and arterial endothelial function, smooth
muscle responses, or carotid wall thickness (P>0.25). By contrast, other lipid
risk factors, such as LDL-cholesterol and LDL-cholesterol/HDL-cholesterol ratio,
were significantly correlated with abnormal arterial function and structure
(P=0.01). These data suggest that elevated Lp(a) levels do not confer
cardiovascular risk by contributing to the early functional or structural changes
of atherosclerosis.
PMID- 10195928
TI - Temporal gradient in shear but not steady shear stress induces PDGF-A and MCP-1
expression in endothelial cells: role of NO, NF kappa B, and egr-1.
AB - Three well-defined laminar flow profiles were created to distinguish the
influence of a gradient in shear and steady shear on platelet-derived growth
factor A (PDGF-A) and monocyte chemoattractant protein-1 (MCP-1) expression in
human endothelial cells. The flow profiles (16 dyne/cm2 maximum shear stress)
were ramp flow (shear stress smoothly transited at flow onset), step flow (shear
stress abruptly applied at flow onset), and impulse flow (shear stress abruptly
applied for 3 s only). Ramp flow induced only minor expression of PDGF-A and did
not increase MCP-1 expression. Step flow increased PDGF-A and MCP-1 mRNA levels 3
and 2-fold at 1.5 hours, respectively, relative to ramp flow. In contrast,
impulse flow increased PDGF-A and MCP-1 expression 6- and 7-fold at 1.5 hours,
and these high levels were sustained for at least 4 hours. These results indicate
that a temporal gradient in shear (impulse flow and the onset of step flow) and
steady shear (ramp flow and the steady component of step flow) stimulates and
diminishes the expression of PDGF-A and MCP-1, respectively. NO synthase
inhibitor NG-amino-L-arginine (L-NAA) was found to markedly enhance MCP-1 and
PDGF-A expression induced by step flow, but decrease their expression induced by
impulse flow, in a dose-dependent manner. NO donor spermine-NONOate (SPR/NO) dose
dependently reduced the MCP-1 and PDGF-A expression induced by impulse flow.
Moreover, impulse flow was found to stimulate sustained (4 hours) I kappa B-alpha
degradation and egr-1 mRNA induction. L-NAA prevented I kappa B-alpha
degradation, whereas SPR/NO increased I kappa B-alpha resynthesis 2 hours after
impulse flow. Both L-NAA and SPR/NO inhibited the impulse flow inducibility of
egr-1 4 hours after the flow stimulation. The results show that both NO induced
by steady shear and NO donor inhibit temporal gradient in shear-induced MCP-1 and
PDGF-A expression by downregulation of their respective transcription factors NF
kappa B and egr-1, whereas NO induced by impulse flow stimulates MCP-1 and PDGF-A
expression by upregulation of the transcription factors. The above findings
suggest distinct roles of temporal gradient in shear and steady shear in
atherogenesis in vivo.
PMID- 10195929
TI - Formation of hyaluronan- and versican-rich pericellular matrix is required for
proliferation and migration of vascular smooth muscle cells.
AB - The accumulation of hyaluronan (HA) and the HA-binding proteoglycan versican
around smooth muscle cells in lesions of atherosclerosis suggests that together
these molecules play an important role in the events of atherogenesis. In this
study we have examined the formation of HA- and versican-rich pericellular
matrices by human aortic smooth muscle cells in vitro, using a particle-exclusion
assay, and the role of the pericellular matrix in cell proliferation and
migration. The structural dependence of the pericellular matrix on HA can be
demonstrated by the complete removal of the matrix with Streptomyces
hyaluronidase. The presence of versican in the pericellular matrix was confirmed
immunocytochemically. By electron microscopy, the cell coat was seen as a tangled
network of hyaluronidase-sensitive filaments decorated with ruthenium red
positive proteoglycan granules. Ninety percent of migrating cells in wounded
cultures, and virtually all mitotic cells, displayed abundant HA- and versican
rich coats. Time-lapse video imaging revealed that HA- and versican-rich
pericellular matrix formation is dynamic and rapid, and coordinated specifically
with cell detachment and mitotic cell rounding. HA oligosaccharides, which
inhibit the binding of HA to the cell surface and prevent pericellular matrix
formation, significantly reduced proliferation and migration in response to
platelet-derived growth factor, whereas larger HA fragments and high molecular
weight HA had no effect. Treatment with HA oligosaccharides also led to changes
in cell shape from a typical fusiform morphology to a more spread and flattened
appearance. These data suggest that organization of HA- and versican-rich
pericellular matrices may facilitate migration and mitosis by diminishing cell
surface adhesivity and affecting cell shape through steric exclusion and the
viscous properties of HA proteoglycan gels.
PMID- 10195930
TI - Poor glycemic control predicts coronary heart disease events in patients with
type 1 diabetes without nephropathy.
AB - Patients with type 1 diabetes mellitus, especially those with nephropathy, are at
increased risk for coronary heart disease (CHD). However, information on the
predictive value of cardiovascular risk factors and the degree of hyperglycemia
with respect to CHD events in patients with type 1 diabetes without nephropathy
is still incomplete. Therefore, we performed a prospective study on risk factors
for CHD in patients with type 1 diabetes free of clinical nephropathy. At
baseline examination, cardiovascular risk factor levels of CHD were determined in
177 patients with type 1 diabetes (87 men and 90 women), age 45 to 64 years at
baseline and >/=30 years at the time of diagnosis of diabetes. These patients
were followed up to 7 years with respect to CHD events. Altogether, 20 patients
with type 1 diabetes (13 men [7.3%] and 7 women [3.9%]) died of CHD and 28
patients with type 1 diabetes (17 men [9.6%] and 11 women [6.2%]) had a serious
CHD event (death from CHD or nonfatal myocardial infarction). In multivariate Cox
regression analysis, a previous history of myocardial infarction (hazard ratio
[HR] and its 95% confidence interval, 8.0 [3.1 to 21.0], P<0.001), high
glycohemoglobin A1 (>10.4%, the highest tertile, HR 5.4 [1.4 to 20.4], P=0.013),
and the duration of diabetes (>16 years, the highest tertile, HR 4.2 [1.3 to
12.9], P=0.013) were the only variables associated with CHD death even after
adjustment for other cardiovascular risk factors. These variables also predicted
the incidence of all CHD events. Our results indicate that poor metabolic control
is a strong predictor of CHD events in patients with late-onset type 1 diabetes
without nephropathy, independently of other cardiovascular risk factors.
PMID- 10195931
TI - Coagulation factors II, V, VII, and X, prothrombin gene 20210G-->A transition,
and factor V Leiden in coronary artery disease: high factor V clotting activity
is an independent risk factor for myocardial infarction.
AB - Increased levels of hemostatic factors and genetic mutations of proteins involved
in coagulation may play a role in the pathogenesis of coronary artery disease. We
investigated clotting activity of factors II (FII:C), V (FV:C), VII (FVII:C), and
X (FX:C), the prothrombin gene 20210G-->A transition, and the factor V Leiden
mutation in 200 survivors of myocardial infarction and in 100 healthy controls.
FV:C (P<0.0001) and FVII:C (P<0.0001) were found to be independent risk factors
for myocardial infarction. High FV:C or high FVII:C combined with smoking or
arterial hypertension increased the relative risk for myocardial infarction up to
50-fold. One of 177 patients (0.6%) and 4 of 89 controls (4.5%) had the
prothrombin 20210 AG genotype. Eleven of 177 patients (6.2%) and 6 of 89 controls
(6.7%) were heterozygous for the factor V Leiden mutation. No homozygous carrier
for these mutations was found. Neither the prothrombin gene 20210G-->A transition
(odds ratio [OR], 0.1; 95% confidence interval [CI], 0.01 to 1.1) nor the factor
V Leiden mutation (OR, 1.0; 95% CI, 0.4 to 2.8) were associated with an increased
relative risk for myocardial infarction. In conclusion, our data indicate that
neither the prothrombin gene 20210G-->A transition nor the factor V Leiden
mutation are risk factors for myocardial infarction. High FVII:C was confirmed to
be an independent risk factor for myocardial infarction. Moreover, we describe
for the first time that high FV:C is an independent risk factor for myocardial
infarction.
PMID- 10195932
TI - Risk of venous thromboembolism and clinical manifestations in carriers of
antithrombin, protein C, protein S deficiency, or activated protein C resistance:
a multicenter collaborative family study.
AB - Deficiencies of antithrombin (AT), protein C (PC) or protein S (PS), and
activated protein C resistance (APCR) are very well-established coagulation
defects predisposing to venous thromboembolism (VTE). We performed a
retrospective cohort family study to assess the risk for VTE in individuals with
AT, PC, or PS deficiency, or APCR. Five hundred thirteen relatives from 9 Italian
centers were selected from 233 families in which the proband had had at least 1
episode of VTE. We calculated the incidence of VTE in the whole cohort and in the
subgroups after stratification by age, sex, and defect. The overall incidence of
VTE (per 100 patient-years) in the group of relatives was 0.52. It was 1.07 for
AT, 0.54 for PC, 0.50 for PS, 0.30 for APCR, and 0.67 in the group with a double
defect. The incidence was associated with age, but not with sex. The mean age at
onset was between 30 and 40 years for all the coagulation defects. Women had the
peak of incidence in the age range of 21 to 40 years, earlier than men. The
lifetime risk for VTE was 4.4 for AT versus APCR, 2.6 for AT versus PS, 2.2 for
AT versus PC, 1.9 for PC versus APCR, and 1.6 for PS versus APCR. AT deficiency
seems to have a higher risk for VTE than the other genetic defects. There is a
relation between age and occurrence of thrombosis for both men and women. The
latter had the peak of incidence earlier than the former.
PMID- 10195933
TI - Antagonistic effects of 17 beta-estradiol, progesterone, and testosterone on Ca2+
entry mechanisms of coronary vasoconstriction.
AB - The clinical observation that coronary artery disease is more common in men and
postmenopausal women than in premenopausal women has suggested cardioprotective
effects of female sex hormones including hormone-mediated coronary vasodilation.
The purpose of this study was to investigate whether the sex hormone-induced
coronary relaxation is caused by inhibition of Ca2+ mobilization into coronary
smooth muscle. The effects of 17beta-estradiol, progesterone, and testosterone on
vascular reactivity and 45Ca2+ influx were tested in deendothelialized coronary
artery strips isolated from castrated male pigs. Prostaglandin F2alpha
(PGF2alpha) (10(-5) mol/L) caused significant, maintained contraction of coronary
artery strips. Caffeine (25 mmol/L), an activator of Ca2+ release from
intracellular stores, caused transient contraction in Ca2+-free solution whereas
membrane depolarization by 96 mmol/L KCl, an activator of Ca2+ entry, caused
maintained contraction in the presence of external Ca2+. The 3 sex hormones
caused significant and concentration-dependent relaxation of PGF2alpha- and 96
mmol/L KCl-induced contractions with 17beta-estradiol being the most effective.
The sex hormones did not significantly affect the transient caffeine contraction
in Ca2+-free solution. In contrast, the sex hormones significantly inhibited the
PGF2alpha- and KCl-induced 45Ca2+ influx. 17beta-Estradiol caused similar
inhibition of PGF2alpha- and KCl-induced contractions, suggesting inhibition of
the same Ca2+ entry mechanism. However, progesterone and testosterone caused
greater relaxation of PGF2alpha-induced contraction than of KCl-induced
contraction. We conclude that in coronary arteries of castrated male pigs, sex
hormones inhibit Ca2+ entry from extracellular space but not Ca2+ release from
intracellular stores. 17beta-Estradiol mainly inhibits Ca2+ entry, whereas
progesterone and testosterone cause coronary relaxation by inhibiting other
mechanisms in addition to Ca2+ entry.
PMID- 10195934
TI - NGF activates similar intracellular signaling pathways in vascular smooth muscle
cells as PDGF-BB but elicits different biological responses.
AB - The signaling pathways that regulate smooth muscle cell migration and
proliferation are incompletely understood. Smooth muscle cells express at least 3
families of receptor tyrosine kinases that mediate cell migration: platelet
derived growth factor (PDGF) receptors, the trk family of neurotrophin receptors,
and insulin-like growth factor 1 receptor. The neurotrophin, nerve growth factor
(NGF), and insulin-like growth factor 1 induce the migration but not the
proliferation of smooth muscle cells, whereas PDGF-BB stimulates both responses.
To determine whether distinct signaling pathways downstream of receptor tyrosine
kinases specifically mediate smooth muscle cell migration or proliferation, the
ligand-induced activation of different signaling pathways in smooth muscle cells
was examined. NGF induces prolonged activation of the Shc/MAP kinase pathway and
phospholipase Cgamma compared with PDGF-BB. The activation of
phosphatidylinositol-3 kinase, however, was 10-fold greater in response to PDGF
BB compared with NGF. Insulin-like growth factor 1 activates only
phosphatidylinositol-3 kinase. Pharmacological inhibitors of phosphatidylinositol
3 kinase, Wortmannin and LY294002, inhibit PDGF-BB and NGF-induced migration,
whereas an inhibitor of MAP kinase kinase, PD98059, has no effect. Our results
suggest that (1) different receptor tyrosine kinases use similar patterns of
activation of signaling pathways to mediate distinct biological outcomes of cell
migration and proliferation, (2) NGF activates signaling proteins in smooth
muscle cells similar to those activated during NGF-induced neuronal
differentiation, and (3) the combinatorial effects of different signaling
pathways are important for the regulation of smooth muscle cell migration and
proliferation. Further studies using mutant trk receptors will help to define the
signal transduction pathways mediating NGF-induced smooth muscle cell migration.
PMID- 10195935
TI - Niacin accelerates intracellular ApoB degradation by inhibiting triacylglycerol
synthesis in human hepatoblastoma (HepG2) cells.
AB - The mechanism by which the potent drug niacin decreases apoB-containing
atherogenic lipoproteins and prevents coronary disease is unclear. Utilizing
human hepatoblastoma (HepG2) cells as an in vitro model, we have examined the
effect of niacin on intracellular degradation of apoB and the regulatory
mechanisms involved in apoB processing. Niacin significantly increased apoB
degradation in a dose- and time-dependent manner. Treatment of HepG2 cells with
calpain inhibitor I [N-acetyl-leucyl-leucyl-norleucinal (ALLN), an inhibitor of
certain protease-mediated apoB degradation], did not alter niacin-induced apoB
degradation. Niacin decreased inhibition of oleate-mediated apoB degradation.
Niacin dose-dependently inhibited the synthesis of both fatty acids and
triacylglycerol (TG) by 20% to 40% as determined by the incorporation of 14C
acetate and 3H-glycerol into fatty acids and TG, respectively. Incubation of
HepG2 cells with niacin significantly inhibited (by 12% to 15%) fatty acid
esterification to produce TG as assessed by the incorporation of 3H-oleic acid
into TG. 14C-acetate incorporation into cholesterol and phospholipids was
unchanged. The activity of microsomal triglyceride transfer protein (MTP), a
carrier protein for lipids, was not altered by pretreatment of cells with niacin.
ApoB mRNA expression and 125I-LDL protein uptake were also unchanged. These data
indicate that niacin accelerates hepatic intracellular post-translational
degradation of apoB by selectively reducing triglyceride synthesis (through
inhibiting both fatty acid synthesis and fatty acid esterification to produce TG)
without affecting ALLN-inhibitable protease- or MTP-mediated intracellular apoB
processing, resulting in decreased apoB secretion and hence lower circulating
levels of the atherogenic lipoproteins.
PMID- 10195936
TI - Effect of cardiopulmonary bypass and heparin on plasma levels of Lp(a) and Apo(a)
fragments.
AB - Fragments of apolipoprotein(a) [apo(a)], the distinctive glycoprotein of
lipoprotein(a) [Lp(a)], are present in human plasma and urine and have been
implicated in the development of atherosclerosis. The mechanism responsible for
the generation of apo(a) fragments in vivo is poorly understood. In this study,
we examined the plasma levels of Lp(a) and apo(a) fragments [or free apo(a)] and
urinary apo(a) in 15 subjects who underwent cardiac surgery necessitating
cardiopulmonary bypass. We also measured the plasma concentration and activity of
polymorphonuclear elastase, an Lp(a)-cleaving enzyme in vitro, and plasma levels
of C-reactive protein. Despite a marked activation of polymorphonuclear cells and
a pronounced inflammatory response, as documented by an 8-fold and a 35-fold
increase in plasma levels of polymorphonuclear elastase and C-reactive protein,
respectively, the proportion of plasma free apo(a) to Lp(a) and urinary excretion
of apo(a) remained unchanged over a 7-day period after surgery, and
polymorphonuclear elastase activity remained undetectable in plasma. No
fragmentation of apo(a) was observed ex vivo in plasma samples collected before
and after surgery. These data indicate that in this model, apo(a) is not
fragmented in plasma and are consistent with the hypothesis that apo(a) fragments
result from a constitutively active tissue mechanism that is not modified by
cardiac surgery with cardiopulmonary bypass.
PMID- 10195937
TI - Depletion of pre beta 1LpA1 and LpA4 particles by mast cell chymase reduces
cholesterol efflux from macrophage foam cells induced by plasma.
AB - Exposure of the LpA1-containing particles present in HDL3 and plasma to a minimal
degree of proteolysis by the neutral protease chymase from exocytosed rat mast
cell granules (granule remnants) leads to a reduction in the high-affinity
component of cholesterol efflux from macrophage foam cells. In this study, we
demonstrate for the first time, a role for mast cell chymase in the depletion of
the lipid-poor minor components of HDL that are specifically involved in reverse
cholesterol transport as initial acceptors of cellular cholesterol. Thus,
addition of proteolytically active granule remnants or human skin chymase to
cholesterol-loaded macrophages of mouse or human origin incubated with human
apoA1, ie, a system in which prebeta1LpA1 is generated, resulted in a sharp
reduction in the high-affinity cholesterol efflux promoted by apoA1. As
determined by nondenaturing 2-dimensional polyacrylamide gradient gel
electrophoresis, the granule remnants effectively depleted the prebeta1LpA1, but
not the alphaLpA1, in HDL3 and in plasma during incubation at 37 degrees C for <1
hour. Incubation of plasma with granule remnants for 1 hour also led to near
disappearance of the LpA4-1 and LpA4-2 particles, but did not affect the
distribution of the apoA2-containing lipoproteins present in the plasma. We
conclude that the reduced ability of granule remnant-treated HDL3 and granule
remnant-treated plasma to induce cholesterol efflux from macrophage foam cells is
caused by selective depletion by mast cell chymase of quantitatively minor A1-
and A4-containing subpopulations of HDL. Because these particles, ie,
prebeta1LpA1 and LpA4, are efficient acceptors of cholesterol from cell surfaces,
their depletion by mast cells may block the initiation of reverse cholesterol
transport in vivo and thereby favor foam cell formation in the arterial intima,
the site of atherogenesis.
PMID- 10195938
TI - Dose-dependent inverse relationship between alcohol consumption and serum Lp(a)
levels in black African males.
AB - Serum or plasma levels of Lp(a) vary widely between individuals and are higher in
Africans and their descendants compared with white persons. In whites, high serum
levels of Lp(a) are associated with the premature development of atherosclerosis.
In both ethnic groups, serum Lp(a) levels are highly genetically determined and
only a few environmental or physiological factors, like testosterone or estrogen,
have been shown to lower serum Lp(a) levels. In whites, alcohol consumption is
associated with lower serum Lp(a) levels. However, the mechanism underlying this
association and whether it holds true for blacks is not known. To address these
questions, we analyzed serum Lp(a) levels in 333 middle-aged males of African
descent from the Seychelles Islands (Indian Ocean). In addition, we analyzed the
size of the apo(a) isoforms and the serum levels of albumin and sex hormones in a
subset of 279 subjects. Serum Lp(a) levels were similar in teetotalers (median,
32.5 mg/dL; n=42) and occasional drinkers (median, 34.1 mg/dL; n=112). In
contrast, individuals consuming 10 to 80 g of ethanol/d (n=83) and heavy drinkers
(>80 g of ethanol/d, n=96) had a 9% and 32% lower median Lp(a) level than
teetotalers, respectively (P=0.01). The size distribution of the apo(a) isoforms
and the mean serum levels of albumin, estradiol, and luteinizing hormone were
similar in teetotalers and occasional drinkers compared with moderate and heavy
drinkers. These latter 2 groups had lower serum levels of testosterone and sex
hormone-binding globulin. These data indicate that alcohol intake is associated
in a dose-dependent manner with lower serum Lp(a) levels in males of African
descent and that this association is not related to the size of the apo(a)
isoforms, to the synthetic function of the liver, or to sex hormone biochemical
status.
PMID- 10195939
TI - Adhesive interaction between P-selectin and sialyl Lewis(x) plays an important
role in recurrent coronary arterial thrombosis in dogs.
AB - Cell adhesion molecules may play an important role in the disease process of
acute coronary syndromes. We have shown a neutralizing anti-P-selectin monoclonal
antibody and a sialyl Lewis(x)-containing oligosaccharide (SLe(x)-OS), an
analogue of selectin ligand on leukocytes, reduce cyclic flow variations (CFVs)
in a canine model of recurrent coronary arterial thrombosis, suggesting the
important interaction between P-selectin and SLex for the pathophysiology of
these syndromes. However, the functional role of these adhesion molecules in the
thrombotic process remains unclear. Therefore, we investigated effects of SLe(x)
OS on CFVs, platelet P-selectin expression, and morphology of the stenotic site
in the same model. Anesthetized open-chest dogs (n=34) were randomly divided into
4 groups after developing CFVs. Dogs intravenously received saline or graded
doses of SLe(x)-OS (5, 20, or 40 mg/kg bolus) infusion followed by a continuous
infusion (5 mg. kg-1. h-1) for 60 minutes. By flow cytometric analysis, P
selectin expression on platelets after CFVs was significantly upregulated during
CFVs. Immunohistochemical analysis revealed the incorporation of platelets with
upregulated P-selectin within thrombi at the stenotic site. Microscopic
observations revealed the presence of numerous platelets adhered to leukocytes at
the stenotic site on the damaged endothelium. SLe(x)-OS significantly reduced
CFVs, inhibited the P-selectin expression on platelets, and prevented the
adherence of platelets and leukocytes. These findings further support the notion
that the adhesive interaction between P-selectin on platelets and SLe(x) on
leukocytes plays an important role in platelet-mediated thrombus formation in
this model.
PMID- 10195940
TI - Structural, functional, and hemodynamic changes of the common carotid artery with
age in male subjects.
AB - Aging of the common carotid artery (CCA) is associated with different principal
structural, functional, and hemodynamic changes, which are often influenced by
several atherosclerotic risk factors, so that it is difficult to estimate the
exclusive effect of aging on this process. Studies dealing with vascular aging of
the CCA usually assess only single, dimensional, or functional parameters,
although it is likely that there are interactions and probably differences
between them. Moreover, regional vascular blood flow characteristics are often
not taken into consideration. Therefore, the aim of the study was to assess the
age-related multiparametric changes of the CCA properties with ultrasound in 69
male subjects between the ages of 16 and 75 (42.4+/-16.5 years), who were
screened for the absence of major atherosclerotic risk factors or existing
vascular disease. As a result, the intima media thickness (0.052 mm/10 y) and
diastolic diameter (0.17 mm/10 y) increased nearly linearly with age (r=0.60,
P<0.001; and r=0.46, P<0.001, respectively). The absolute diastolic/systolic
diameter change diminished by 0.10 mm/10 y (r=-0. 73, P<0.001) and peak expansion
velocity dropped by 0.12 cm/s per 10 years (r=-0.62, P<0.001) highly
significantly with age. The peak blood flow velocity decreased continuously with
age (r=-0.67, P<0. 00) by 9.3 cm/s per 10 years. According to multiple regression
analysis, peak blood flow velocity seems to reflect the changes of several
structural and functional parameters in one; intima-media thickness was
determined by diastolic arterial diameter and age as independent variables. The
data indicate that a multiparametric assessment may contribute to a better
understanding of vascular aging and might be the basis for further studies to
evaluate the association of atherosclerotic risk factors and/or major vascular
disease with local changes in the CCA.
PMID- 10195941
TI - Mutations in promoter region of thrombomodulin and venous thromboembolic disease.
AB - The present study was designed to analyze the thrombomodulin proximal promoter
region spanning nucleotides -293 to -12 to search for polymorphisms that could
modify thrombomodulin gene expression in patients with venous thromboembolic
disease. The study population comprised 205 patients and 394 healthy subjects of
similar age and sex distribution. No polymorphisms and only 1 point mutation (G
33A) were found. The G-33A mutation was present at the heterozygous state in 2
patients and in 1 control. Being more frequent in the patients (0.97%) than in
the controls (0.25%), the G-33A mutation might be a risk factor for venous
thrombosis. To investigate the effect of this mutation on the thrombomodulin
promoter activity, the proximal promoter region of the gene (bearing or not
bearing the G-33A mutation) was inserted into a promotorless expression vector,
upstream of the firefly luciferase gene, and transiently transfected into
EA.hy926 endothelial cells. Under the conditions of the assay, the G-33A mutation
mildly decreased the promoter activity. This study confirms that abnormalities of
the thrombomodulin proximal promoter are not frequent in patients with venous
thromboembolism.
PMID- 10195943
TI - Omega-3 fatty acids in adipose tissue and risk of myocardial infarction: the
EURAMIC study.
AB - Omega-3 fatty acids have potential antiatherogenic, antithrombotic, and
antiarrhythmic properties, but their role in coronary heart disease remains
controversial. To evaluate the association of omega-3 fatty acids in adipose
tissue with the risk of myocardial infarction in men, a case-control study was
conducted in eight European countries and Israel. Cases (n=639) included patients
with a first myocardial infarction admitted to coronary care units within 24
hours from the onset of symptoms. Controls (n=700) were selected to represent the
populations originating the cases. Adipose tissue levels of fatty acids were
determined by capillary gas chromatography. The mean (+/-SD) proportion of alpha
linolenic acid was 0.77% (+/-0.19) of fatty acids in cases and 0.80% (+/-0.19) of
fatty acids in controls (P=0.01). The relative risk for the highest quintile of
alpha-linolenic acid compared with the lowest was 0.42 (95% confidence interval
[CI] 0.22 to 0.81, P-trend=0.02). After adjusting for classical risk factors, the
relative risk for the highest quintile was 0.68 (95% CI 0.31 to 1.49, P
trend=0.38). The mean proportion of docosahexaenoic acid was 0.24% (+/-0.13) of
fatty acids in cases and 0.25% (+/-0.13) of fatty acids in controls (P=0. 14),
with no evidence of association with risk of myocardial infarction. In this large
case-control study we could not detect a protective effect of docosahexaenoic
acid on the risk of myocardial infarction. The protective effect of alpha
linolenic acid was attenuated after adjusting for classical risk factors (mainly
smoking), but it deserves further research.
PMID- 10195942
TI - Increased atherosclerosis in ApoE and LDL receptor gene knock-out mice as a
result of human cholesteryl ester transfer protein transgene expression.
AB - The plasma cholesteryl ester transfer protein (CETP) plays a major role in the
catabolism of HDL cholesteryl ester (CE). CETP transgenic mice have decreased HDL
cholesterol levels and have been reported to have either increased or decreased
early atherosclerotic lesions. To evaluate the impact of CETP expression on more
advanced forms of atherosclerosis, we have cross-bred the human CETP transgene
into the apoE knock-out (apoE0) background with and without concomitant
expression of the human apo A-I transgene. In this model the CETP transgene is
induced to produce plasma CETP levels 5 to 10 times normal human levels. CETP
expression resulted in moderately reduced HDL cholesterol (34%) in apoE0 mice and
markedly reduced HDL cholesterol (76%) in apoE0/apoA1 transgenic mice. After
injection of radiolabeled HDL CE, the CETP transgene significantly delayed the
clearance of CE radioactivity from plasma in apoE0 mice, but accelerated the
clearance in apoE0/apoA1 transgenic mice. ApoE0/CETP mice displayed an increase
in mean atherosclerotic lesion area on the chow diet (approximately 2-fold after
2 to 4 months, and 1.4- to 1.6-fold after 7 months) compared with apoE0 mice
(P<0.02). At 7 months apoA1 transgene expression resulted in a 3-fold reduction
in mean lesion area in apoE0 mice (P<0.001). In the apoE0/apoA1 background, CETP
produced an insignificant 1.3- to 1.7-fold increase in lesion area. In further
studies the CETP transgene was bred onto the LDL receptor knock-out background
(LDLR0). After 3 months on the Western diet, the mean lesion area was increased
1.8-fold (P<0.01) in LDLR0/CETP mice, compared with LDLR0 mice. These studies
indicate that CETP expression leads to a moderate increase in atherosclerosis in
apoE0 and LDLR0 mice, and suggest a proatherogenic effect of CETP activity in
metabolic settings in which clearance of remnants or LDL is severely impaired.
However, apoA1 overexpression has more dramatic protective effects on
atherosclerosis in apoE0 mice, which are not significantly reversed by
concomitant expression of CETP.
PMID- 10195944
TI - Prooxidant and antioxidant activities of macrophages in metal-mediated LDL
oxidation: the importance of metal sequestration.
AB - Murine macrophages incubated in metal-supplemented RPMI could block or promote
oxidation of low-density lipoprotein (LDL) depending on the degree of metal
supplementation. Only at high concentrations of Cu (1 micromol/L) and Fe (30
micromol/L) were cells prooxidant, leading to an accelerated rate of LDL
oxidation over that measured in comparable cell-free media. At lower
concentrations of Cu and Fe in RPMI, LDL oxidation in the presence of macrophages
was inhibited relative to the cell-free condition. This appeared to be dependent
on a stable modification of the culture medium, because preconditioning of media
by incubation with macrophages could also decrease their capacity to sustain
subsequent cell-free LDL oxidation. This was due, in part, to a removal of metal
from the media during preconditioning. However, resupplementation of media with
metals did not fully restore oxidative capacity, indicating that other cell
dependent antioxidant modifications occurred. This did not involve significant
alterations to the thiol content of the media. This study highlights the
complexity of the role that cells such as macrophages have with regards to LDL
oxidation in vitro and demonstrate that there are both antioxidative and
prooxidative components.
PMID- 10195945
TI - Alpha-tocopherol decreases interleukin-1 beta release from activated human
monocytes by inhibition of 5-lipoxygenase.
AB - Cardiovascular disease is the leading cause of morbidity and mortality in
westernized populations. Low levels of alpha-tocopherol (AT) are associated with
increased incidence of atherosclerosis and increased intakes appear to be
protective. Recently, we showed that supplementation with AT resulted in
significant decreases in monocyte superoxide anion release, lipid oxidation,
interleukin-1 beta (IL-1 beta) release, and adhesion to endothelium. The
reduction in superoxide and lipid oxidation by AT seemed to be mediated by
inhibition of protein kinase C. The aim of this study was to investigate the
mechanism(s) by which AT inhibits IL-1 beta release. Potential mechanisms
examined included its effect as an antioxidant and its inhibitory effects on
protein kinase C and the cyclooxygenase-lipoxygenase pathways. Although AT
decreased superoxide release from activated monocytes, superoxide dismutase and
catalase had no effect on IL-1 beta release. Also, a similar antioxidant, beta
tocopherol, had no effect on IL-1 beta release. The protein kinase C inhibitor,
bisindolylmaleimide, did not inhibit IL-1 beta release from activated monocytes,
in spite of AT decreasing protein kinase C activity. Leukotriene B4, a major
product of 5-lipoxygenase, has been shown to augment IL-1beta release. In the
presence of AT, a significant reduction in leukotriene B4 and IL-1 beta levels
was observed, which was reversed by the addition of leukotriene B4. Similar
observations were seen with specific inhibitors of 5-lipoxygenase. The product of
cyclooxygenase, prostaglandin E2, has been shown to inhibit IL-1 beta activity in
some systems. However, AT had no significant effect on prostaglandin E2 levels in
activated monocytes. In the presence of indomethacin, a cyclooxygenase inhibitor,
AT inhibited IL-1 beta activity. Also, AT had no effect on IL-1 beta mRNA levels
or stability, suggesting a posttranscriptional effect. Thus, in activated human
monocytes, AT exerts a novel biological effect of inhibiting the release of the
proinflammatory cytokine, IL-1 beta, via inhibition of the 5-lipoxygenase
pathway.
PMID- 10195946
TI - Pleiotropy and genotype by diet interaction in a baboon model for
atherosclerosis: a multivariate quantitative genetic analysis of HDL subfractions
in two dietary environments.
AB - We investigated dietary effects on pleiotropic relationships among 3 HDL
cholesterol (C) subfractions (HDL1-C, HDL2-C, and HDL3-C; levels quantified by
gradient gel electrophoresis) for 942 pedigreed baboons (Papio hamadryas) who
were fed a basal (Chow) diet and a high cholesterol, saturated fat (HCSF)
challenge diet. Using multivariate maximum likelihood methods we estimated
heritabilities for all 6 traits, genetic and environmental correlations (rhoG and
rhoE) between them, and the additive genetic variance of each subfraction's
response to the diets. On the Chow diet, genetic correlations between the 3
subfractions were significant, and we observed complete pleiotropy between HDL1-C
and HDL3-C (rhoG=-0.81). On the HCSF diet, only the genetic correlation between
HDL1-C and HDL3-C (rhoG=-0.61) was significant. Genetic correlations between
individual subfractions on the Chow and HCSF diets did not differ significantly
from 1.0, indicating that the same additive genes influenced each subfraction's
levels regardless of diet. However, the additive genetic variance of response to
the diets was highly significant for HDL1-C and HDL2-C, but not for HDL3-C.
Similar sets of genes influence variation in the 3 HDL subfractions on the Chow
diet, and the same set influences variation in each subfraction on the HCSF diet.
However, the expression of genes influencing HDL1-C and HDL2-C is altered by the
HCSF diet, disrupting the pleiotropy observed between the 3 subfractions on the
Chow diet.
PMID- 10195947
TI - Increased platelet aggregability associated with platelet GPIIIa PlA2
polymorphism: the Framingham Offspring Study.
AB - The platelet glycoprotein IIb/IIIa (GP IIb/IIIa) plays a pivotal role in platelet
aggregation. Recent data suggest that the PlA2 polymorphism of GPIIIa may be
associated with an increased risk for cardiovascular disease. However, it is
unknown if there is any association between this polymorphism and platelet
reactivity. We determined GP IIIa genotype and platelet reactivity phenotype data
in 1422 subjects from the Framingham Offspring Study. Genotyping was performed
using PCR-based restriction fragment length polymorphism analysis. Platelet
aggregability was evaluated by the Born method. The threshold concentrations of
epinephrine and ADP were determined. Allele frequencies of PlA1 and PlA2 were
0.84 and 0.16, respectively. The presence of 1 or 2 PlA2 alleles was associated
with increased platelet aggregability as indicated by incrementally lower
threshold concentrations for epinephrine and ADP. For epinephrine, the mean
concentrations were 0.9 micromol/L (0.9 to 1.0) for homozygous PlA1, 0.7 mmol/L
(0.7 to 0.9) for the heterozygous PlA1/PlA2, and 0.6 micromol/L (0.4 to 1.0) for
homozygous PlA2 individuals, P=0.009. The increase in aggregability induced by
epinephrine remained highly significant (P=0.007) after adjustment for
covariates. For ADP-induced aggregation, the respective mean concentrations were
3.1 micromol/L (3.0 to 3.2), 3.0 micromol/L (2.9 to 3.2), and 2.8 micromol/L (2.4
to 3.3); P=0.19 after adjustment for covariates. Our findings indicate that
molecular variants of the gene encoding GP IIIa play a role in platelet
reactivity in vitro. Our observations are compatible with and provide an
explanation for the reported association of the PlA2 allotype with increased risk
for cardiovascular disease.
PMID- 10195948
TI - Kevorkian and assisted death in the United States.
PMID- 10195949
TI - Prisoners: an end to second class health care?
PMID- 10195950
TI - Medical fiction.
PMID- 10195951
TI - Doing something about tuberculosis.
PMID- 10195952
TI - The largest mass gathering.
PMID- 10195954
TI - Breast cancer treatment delays affect survival
PMID- 10195953
TI - Will the NHS pay awards help recruitment?
PMID- 10195955
TI - Strokes at night more likely to delay care.
PMID- 10195956
TI - In brief
PMID- 10195957
TI - Cholesterol lowering margarine launched in united kingdom
PMID- 10195958
TI - Spain tackles eating disorders.
PMID- 10195959
TI - UN responding slowly to Kosovo refugee crisis.
PMID- 10195960
TI - Germany plans to make GPs gatekeepers.
PMID- 10195961
TI - Canada's drug plan hits old, mentally ill, and those on welfare.
PMID- 10195962
TI - Drug companies criticised for exaggeration.
PMID- 10195963
TI - UK appeal upholds clinical responsibility of managers.
PMID- 10195964
TI - Fertility patterns after appendicectomy: historical cohort study.
AB - OBJECTIVE: To examine fertility patterns in women who had their appendix removed
in childhood. DESIGN: Historical cohort study with computerised data and
fertility data for this cohort and for an age matched cohort of women from the
Swedish general population. The cohorts were followed to 1994. SETTING: General
population. PARTICIPANTS: 9840 women who were under 15 years when they underwent
appendicectomy between 1964 and 1983; 47 590 control women. MAIN OUTCOME
MEASURES: Diagnoses at discharge. Distributions of age at birth of first child
among women with perforated and non-perforated appendix and women who underwent
appendicectomy but were found to have a normal appendix compared with control
women by using survival analysis methods. Parity distributions at the latest
update of the registry were also examined. RESULTS: Women with a history of
perforated appendix had a similar rate of first birth as the control women
(adjusted hazard ratio 0.95; 95% confidence interval 0.88 to 1. 04) and had a
similar distribution of parity at the end of follow up. Women who had had a
normal appendix removed had an increased rate of first births (1.48; 1.42 to
1.54) and on average had their first child at an earlier age and reached a higher
parity than control women. CONCLUSION: A history of perforated appendix in
childhood does not seem to have long term negative consequences on female
fertility. This may have important implications for the management of young women
with suspected appendicitis as the liberal attitude to surgical explorations with
a subsequently high rate of removal of a normal appendix is often justified by a
perceived increased risk of infertility after perforation. Women whose appendix
was found to be normal at appendicectomy in childhood seem to belong to a
subgroup with a higher fertility than the general population.
PMID- 10195965
TI - Ethnic differences in incidence of stroke: prospective study with stroke
register.
AB - OBJECTIVE: To identify ethnic differences in the incidence of first ever stroke.
DESIGN: A prospective community stroke register (1995-6) with multiple
notification sources. Pathological classification of stroke in all cases was
based on brain imaging or necropsy data. Rates were standardised to European and
world populations and adjusted for age, sex, and social class in multivariate
analysis. SETTING: A multi-ethnic population of 234 533 in south London, of whom
21% are black. RESULTS: 612 strokes were registered. The crude annual incidence
rate was 1.3 strokes per 1000 population per year (95% confidence interval 1.20
to 1.41) and 1.25 per 1000 population per year (1.15 to 1.35) age adjusted to the
standard European population. Incidence rates adjusted for age and sex were
significantly higher in black compared with white people (P<0.0001), with an
incidence rate ratio of 2.21 (1.77 to 2.76). In multivariable analysis increasing
age (P<0.0001), male sex (P<0.003), black ethnic group (P<0.0001), and lower
social class (P<0.0001) in people aged 35-64 were independently associated with
an increased incidence of stroke. CONCLUSIONS: Incidence rates of stroke are
higher in the black population; this is not explained by confounders such as
social class, age, and sex. Ethnic differences in genetic, physiological, and
behavioural risk factors for stroke require further elucidation to aid
development of effective strategies for stroke prevention in multi-ethnic
communities.
PMID- 10195966
TI - Effects of a drug overdose in a television drama on presentations to hospital for
self poisoning: time series and questionnaire study.
AB - OBJECTIVES: To determine whether a serious paracetamol overdose in the medical
television drama Casualty altered the incidence and nature of general hospital
presentations for deliberate self poisoning. DESIGN: Interrupted time series
analysis of presentations for self poisoning at accident and emergency
departments during three week periods before and after the broadcast.
Questionnaire responses collected from self poisoning patients during the same
periods. SETTING: 49 accident and emergency departments and psychiatric services
in United Kingdom collected incidence data; 25 services collected questionnaire
data. SUBJECTS: 4403 self poisoning patients; questionnaires completed for 1047.
MAIN OUTCOME MEASURES: Change in presentation rates for self poisoning in the
three weeks after the broadcast compared with the three weeks before, use of
paracetamol and other drugs for self poisoning, and the nature of overdoses in
viewers of the broadcast compared with non-viewers. RESULTS: Presentations for
self poisoning increased by 17% (95% confidence interval 7% to 28%) in the week
after the broadcast and by 9% (0 to 19%) in the second week. Increases in
paracetamol overdoses were more marked than increases in non-paracetamol
overdoses. Thirty two patients who presented in the week after the broadcast and
were interviewed had seen the episode-20% said that it had influenced their
decision to take an overdose, and 17% said it had influenced their choice of
drug. The use of paracetamol for overdose doubled among viewers of Casualty after
the episode (rise of 106%; 28% to 232%). CONCLUSIONS: Broadcast of popular
television dramas depicting self poisoning may have a short term influence in
terms of increases in hospital presentation for overdose and changes in the
choice of drug taken. This raises serious questions about the advisability of the
media portraying suicidal behaviour.
PMID- 10195967
TI - All in the family
PMID- 10195968
TI - Effects of a drug overdose in a television drama on knowledge of specific dangers
of self poisoning: population based surveys.
PMID- 10195969
TI - TB or not TB
PMID- 10195970
TI - Time
PMID- 10195973
TI - The wrong notes
PMID- 10195972
TI - Computer support for determining drug dose: systematic review and meta-analysis.
AB - OBJECTIVE: To review the effectiveness of computer support for determining
optimum drug dose. DESIGN: Systematic review of comparative studies where
computers gave advice to clinicians on the most appropriate drug dose. Search
methods used were standard for the Cochrane Collaboration on Effective
Professional Practice. SUBJECTS: Comparative studies conducted worldwide and
published between 1966 and 1996. MAIN OUTCOME MEASURES: For qualitative review,
relative percentage differences were calculated to compare effects of computer
support in different settings. For quantitative data, effect sizes were
calculated and combined in meta-analyses. RESULTS: Eighteen studies met the
inclusion criteria. The drugs studied were theophylline, warfarin, heparin,
aminoglycosides, nitroprusside, lignocaine, oxytocin, fentanyl, and midazolam.
The computer programs used individualised pharmacokinetic models to calculate the
most appropriate dose. Meta-analysis of data from 671 patients showed higher
blood concentrations of drug with computer support (effect size 0.69, 95%
confidence interval 0.36 to 1.02) and reduced time to achieve therapeutic control
(0.44, 0.17 to 0.71). The total dose of drug used was unchanged, and there were
fewer unwanted effects of treatment. Five of six studies measuring outcomes of
care showed benefit from computer assistance. CONCLUSIONS: This review suggests
that using computers to determine the correct dose of certain drugs in acute
hospital settings is beneficial. Computers may give doctors the confidence to use
higher doses when necessary, adjusting the drug dose more accurately to
individual patients. Further research is necessary to evaluate the benefits in
general use.
PMID- 10195971
TI - Preventing injuries in children: cluster randomised controlled trial in primary
care.
AB - OBJECTIVE: To assess the effectiveness of safety advice at child health
surveillance consultations, provision of low cost safety equipment to families
receiving means tested state benefits, home safety checks, and first aid training
on frequency and severity of unintentional injuries in children at home. DESIGN:
Cluster randomised controlled trial. SETTING: 36 general practices in Nottingham.
SUBJECTS: All children aged 3-12 months registered with participating practices.
INTERVENTIONS: A package of safety advice at child health surveillance
consultations at 6-9, 12-15, and 18-24 months; provision of low cost safety
equipment to families on means tested state benefits; and home safety checks and
first aid training by health visitors. OUTCOME MEASURES: Primary outcomes
measures were frequency and severity of medically attended injuries. Secondary
outcome measures were self reported safety practices, possession and use of
safety equipment, knowledge and confidence in dealing with first aid, and
perceptions of risk of injury and risk of hazards assessed by postal
questionnaire at baseline and follow up at 25 months. RESULTS: At baseline, both
groups had similar risk factors for injury, sociodemographic characteristics,
safety practices, possession and use of safety equipment, knowledge and
confidence in dealing with first aid, and perceptions of risk. No significant
difference was found in frequency of at least one medically attended injury (odds
ratio 0.97, 95% confidence interval 0.72 to 1.30), at least one attendance at an
accident and emergency department for injury (1.02, 0.76 to 1.37), at least one
primary care attendance for injury (0.75, 0.48 to 1.17), or at least one hospital
admission for injury (0.69, 0.42 to 1.12). No significant difference in the
secondary outcome measures was found between the intervention and control groups.
CONCLUSIONS: The intervention package was not effective in reducing the frequency
of minor unintentional injuries in children at home, and larger trials are
required to assess the effect on more severe injuries.
PMID- 10195974
TI - Recent advances in haematology.
PMID- 10195976
TI - The royal academy exhibition
PMID- 10195975
TI - ABC of labour care: induction.
PMID- 10195977
TI - Probiotics and prebiotics: can regulating the activities of intestinal bacteria
benefit health?
PMID- 10195978
TI - The World Bank on world health: under fire.
PMID- 10195979
TI - Smear tests were not on trial but should have been.
PMID- 10195980
TI - Postcoital testing. Criterion for positive test was not given.
PMID- 10195981
TI - Value of breast imaging in women with painful breasts. Negative results are not
reassuring.
PMID- 10195982
TI - More on the Bristol affair. The affair has had several serious negative outcomes.
PMID- 10195983
TI - Use of asthma drugs is less among women pregnant with boys rather than girls.
PMID- 10195984
TI - Australian university students agree with Clinton's definition of sex.
PMID- 10195985
TI - Prevalence of smoking among pregnant women is lower in Italy than England.
PMID- 10195986
TI - The profession, not the media, should assess where Kasai portoenterostomy should
be performed.
PMID- 10195987
TI - Political correctness is behind proposed appraisal system.
PMID- 10195988
TI - Prescribing antibiotics for sore throats. Doctor uses different method from
authors.
PMID- 10195989
TI - Emyr wyn jones
PMID- 10195990
TI - Cardiovascular disease in the octogenarian and beyond
PMID- 10195991
TI - Safety, health and environmental hazards at the workplace
PMID- 10195993
TI - Website of the week
PMID- 10195992
TI - Journal of clinical effectiveness
PMID- 10195994
TI - A step towards effective self regulation
PMID- 10195996
TI - Fertility effects need not be considered in women with suspected appendicitis
PMID- 10195995
TI - May I take this opportunity
PMID- 10195997
TI - Black people are twice as likely as white people to suffer stroke
PMID- 10195998
TI - Overdoses on television may encourage others
PMID- 10195999
TI - Watching medical soaps may increase medical knowledge
PMID- 10196000
TI - Intervention package did not reduce minor injuries in children
PMID- 10196001
TI - Computer support for determining drug doses improves outcomes
PMID- 10196002
TI - Morbidity and mortality in redefining adequacy of peritoneal dialysis: a step
beyond the National Kidney Foundation Dialysis Outcomes Quality Initiative.
AB - The National Kidney Foundation Dialysis Outcomes Quality Initiative (NKF-DOQI)
Peritoneal Dialysis (PD) Adequacy Work Group intentionally limited the scope of
its work to address adequacy in terms of small-solute removal. This decision was
based on the need for rigorous evidence and that mortality is the most objective
parameter in the literature. This review attempts to more broadly redefine the
concept of the adequacy of PD, particularly as it relates to the most common
general medical problems that PD patients experience; namely, cardiovascular
disease and malnutrition. Whereas we are sensitive to the developmental process
of the NKF-DOQI, we are critical that the definition of adequacy may be too
narrow, leading clinicians to overlook other important morbidities. We have
reiterated the evidence that suggests a weekly solute clearance (Kt/Vurea) of 1.7
or greater is associated with better patient survival. The arguments to target a
greater Kt/Vurea of 2.0 are challenged, yet the concept is ultimately supported.
Because cardiovascular disease is the cause of death in half of all patients with
end-stage renal disease, dialysis adequacy must be defined, in part, by the
potential of that therapy to diminish cardiovascular maladies. Blood pressure,
volume, left ventricular hypertrophy, and dyslipidemias are discussed in this
context. Lastly, assumptions that increasing total solute clearance leads to
improved nutrition in PD patients are challenged. We have attempted to expand on
what the NKF-DOQI did not include, and we urge the dialysis community to seek the
answers to the many controversies that remain. We need to redefine the adequacy
of PD in a holistic manner and find outcome parameters that are not as final as
death.
PMID- 10196003
TI - Role of fermentable carbohydrate supplements with a low-protein diet in the
course of chronic renal failure: experimental bases.
AB - During the past few years, considerable attention has been given to the impact of
nutrition on kidney disease. The question arises of whether the effect of a
moderate dietary protein restriction could be reinforced by enrichment of the
diet with fermentable carbohydrates. Feeding fermentable carbohydrates may
stimulate the extrarenal route of nitrogen (N) excretion through the fecal route.
Such an effect has been reported in several species, including healthy humans and
patients with chronic renal failure (CRF). Furthermore, studies of these subjects
show that the greater fecal N excretion during the fermentable carbohydrate
supplementation period was accompanied by a significant decrease in plasma urea
concentration. In animal models of experimental renal failure, the consumption of
diets containing fermentable carbohydrates results in a greater rate of urea N
transfer from blood to the cecal lumen, where it is hydrolyzed by bacterial
urease before subsequent microflora metabolism and proliferation. Therefore, this
results in a greater fecal N excretion, coupled with a reduction in urinary N
excretion and plasma urea concentration. Because elevated concentrations of serum
urea N have been associated with adverse clinical symptoms of CRF, these results
suggest a possible usefulness of combining fermentable carbohydrates with a low
protein diet to increase N excretion through the fecal route. Further
investigations in this population of patients of whether fermentable
carbohydrates in the diet may be beneficial in delaying or treating the symptoms
and chronic complications of CRF will certainly emerge in the future. This should
be realized without adversely affecting nutritional status and, as far as
possible, by optimizing protein intake for the patients without being detrimental
to renal function.
PMID- 10196004
TI - Role of physician assistants in dialysis units and nephrology.
AB - We surveyed physician assistants who work in nephrology to report their
experience level, primary employer, salary, job responsibilities, and job
satisfaction. Additional data were obtained from the Nephrology Manpower Study.
The 67 responding physician assistants of 97 surveyed have 10.8 +/- 6.5 years
(mean +/- standard deviation) total experience (6.2 +/- 5.0 years in nephrology).
Typically, nephrologists (56.1%) or hospitals (30.3%) employ them. The majority
(74%) earn $49,999 to $75,000; 79.1% work in outpatient units, 52.4% in inpatient
units, 52.4% in hospitals, 43.3% in outpatient offices, and 23.9% in transplant
units. In outpatient units, they manage 111 +/- 111 patients, mostly in free
standing (71.1%), for-profit (69.7%), corporately owned (87.3%) units in urban
(80%) or suburban (18%) areas. Most (>85%) manage all dialysis- and nondialysis
related problems, including health maintenance; 84.3% are contacted first by
staff, and 78% see patients more often than physicians. Of nephrologists who
responded to the Manpower Study, 8.9% work with physician assistants and 20.7%
work with nurse practitioners. Nephrologists in academic practice or private
nephrology groups are more likely to use physician assistants (P < 0.05) and
nurse practitioners (P < 0.005) than those in solo practice or multispecialty
groups. Nephrologists with physician assistants (33.8 +/- 19.5 v 41.7 +/- 16.8
h/wk) or nurse practitioners (35.8 +/- 18.1 v 42.7 +/- 16.9 h/wk) tended to spend
less time in direct patient care than those without physician extenders (P <
0.001). Nephrologists with renal fellows, however, spent the least time of all in
direct patient care (30.0 +/- 15.9 v 47.3 +/- 14.9 h/wk; P < 0.001). Physician
assistants can perform nearly all the medical tasks in dialysis units. They may
offer one approach to providing effective and complete care for patients if
nephrology manpower becomes limited.
PMID- 10196005
TI - Collapsing glomerulopathy: clinical characteristics and follow-up.
AB - In 1986, Weiss et al reported a group of patients with nephrotic syndrome,
progressive chronic renal failure, and the histopathologic features of glomerular
capillary collapse. Similar lesions are often described in human immunodeficiency
virus (HIV) nephropathy. We evaluated 893 consecutive nontransplant renal
biopsies performed in our department and the follow-up of the patients at our
outpatient service. Sixteen specimens were identified with the pathological
features of collapsing glomerulopathy (focal segmental or global glomerular
capillary collapse and visceral epithelial cell hyperplasia), with no evidence of
HIV infection and/or intravenous drug abuse. Their clinical characteristics were
analyzed and compared with a group of 29 patients with noncollapsing focal
segmental glomerulosclerosis (FSGS). The follow-up period of both patient groups
was 5 +/- 1.46 years. The Kaplan-Meier life table method was used to present
survival of the patients. The age of both groups was similar, 34 +/- 4 years
(mean +/- standard error of the mean) for patients with collapsing glomerulopathy
and 35 +/- 3 years for those with FSGS. The serum creatinine level was greater in
patients with collapsing glomerulopathy (183 +/- 31 micromol/L) compared with
those with FSGS (115 +/- 18 micromol/L), but the difference was not significant
(P = 0.0504). The difference in proteinuria was not significant (P = 0.7668); it
was 5.83 +/- 0.74 g/d in patients with collapsing glomerulopathy and 5.42 +/-
0.84 g/d in those with focal sclerosing glomerulonephritis. The difference in
systolic (P = 0.4) and diastolic blood pressure (P = 0.556) was also not
significant. Survival of the patients with collapsing glomerulopathy was worse
than that of patients with FSGS (P = 0.025). Renal function survived 5 years in
40% of the patients with FSGS, but patients with collapsing glomerulopathy had no
renal function survival. Our data suggest that idiopathic collapsing
glomerulopathy is a distinct clinicopathologic entity with similar clinical
features to focal sclerosing glomerulonephritis, but a worse prognosis and a
rapidly progressive course toward end-stage renal disease.
PMID- 10196006
TI - Collapsing glomerulopathy in renal allografts: a morphological pattern with
diverse clinicopathologic associations.
AB - We reviewed the clinical and pathological characteristics of seven patients with
collapsing glomerulopathy (CG) in renal allograft biopsy specimens. All patients
underwent biopsies for graft dysfunction. Two patients had nephrotic proteinuria
(protein, >3.5 g/24 h), whereas all others had only modest or insignificant
proteinuria. In five of seven patients, additional pathological processes,
including microvascular injury, acute rejection, recurrent diabetic nephropathy,
and immune complex glomerulonephritis, were present, each of which likely
contributed to graft dysfunction and proteinuria. None of the patients in this
series had nephrotic syndrome solely attributable to CG. Three biopsy specimens
had features consistent with chronic rejection. The development of CG in renal
allograft biopsy specimens was associated with graft dysfunction and a high rate
of graft loss. These findings emphasize the prognostic significance of CG in
renal allografts and suggest that CG may result from diverse pathogenic
mechanisms.
PMID- 10196007
TI - Ambulatory blood pressure monitoring and interdialytic weight gain in children
receiving chronic hemodialysis.
AB - Volume overload appears to induce hypertension in hemodialysis patients, yet
studies of the effect of hydration status on interdialytic blood pressure (BP)
have yielded contradictory results. We measured interdialytic BP by ambulatory BP
monitoring (ABPM) during inpatient fluid restriction in 12 children receiving
chronic hemodialysis to describe the overall BP pattern and to determine the
effect of weight gain on BP change. Weight was measured on admission and four
times each day. For each weight, casual BP was measured and compared with the
mean of 3 hours of ABPM surrounding the weight measurement. Sleep BP decreased
from daytime BP by 6% for systolic BP (SBP) and 11% for diastolic BP (DBP). Sleep
loads were greater than daytime loads (P < 0.01) for SBP (53% v 28%) and DBP (57%
v 27%). Overall, 58% (7 of 12) of the patients had sleep SBP load greater than
50%, and 67% (8 of 12) of the patients had sleep DBP load greater than 50%.
Casual and ABPM measurements of BP showed moderate correlations for SBP (r =
0.51) and DBP (r = 0.46) and mean differences between methods of 6.3 +/- 13.2 mm
Hg and -1.4 +/- 12.6 mm Hg, respectively. Increases in interdialytic weight were
positively associated with increases in SBP (r = 0.41; P < 0.001), and
interdialytic BP changes varied closely with corresponding weight changes. We
conclude that in children receiving chronic hemodialysis: (1) sleep BP decreases
are attenuated and sleep BP loads are elevated, (2) casual BP correlates poorly
with ABPM, and (3) interdialytic weight and BP are related.
PMID- 10196008
TI - Blood pressure, antihypertensive medication, and atherosclerotic renal artery
stenosis.
AB - The relationship between atherosclerotic renal artery stenosis (ARAS) and blood
pressure control remains poorly understood. Duplex ultrasonography is a
noninvasive method for detecting and grading ARAS. The purpose of this study was
to characterize the relationship between the degree of ARAS, levels of blood
pressure, and control of blood pressure with antihypertensive medication. A cross
sectional analysis was performed on 139 patients with ARAS. All patients had at
least one diseased renal artery by duplex ultrasound. Renal arteries were
classified as normal, less than 60% stenosis, or 60% or greater (high-grade)
stenosis. Data regarding blood pressure, coexisting risk factors, and medications
were collected. The extent of ARAS was significantly associated with progressive
elevation of the systolic blood pressure, whereas the diastolic component was
elevated in the case of unilateral high-grade stenosis: no high-grade stenoses,
153 +/- 22/81 +/- 10 mm Hg; unilateral high-grade stenosis, 162 +/- 22/86 +/- 9
mm Hg; and bilateral high-grade stenoses, 174 +/- 27/82 +/- 9 mm Hg (P = 0.002
systolic; P = 0.02 diastolic). Eighty-two percent of the patients were taking
known antihypertensive medications. Angiotensin-converting enzyme inhibitor
(ACEI) usage versus nonusage was associated with a significantly lower systolic
(157 +/- 27 v 169 +/- 22 mm Hg; P = 0.03) and diastolic (79 +/- 9 v 85 +/- 9 mm
Hg; P = 0.001) blood pressure. The effect of ACEI usage was observed in patients
with high-grade ARAS. None of the other classes of antihypertensive medications
were associated with significantly lower blood pressure. In patients with ARAS,
blood pressure levels were correlated with the severity of renal artery disease.
Patients taking ACEIs had significantly lower blood pressures, and the effect of
ACEI usage was strongest among patients with unilateral ARAS.
PMID- 10196009
TI - Role of home blood pressure monitoring in hemodialysis patients.
AB - To investigate the use of manual home blood pressure (BP) monitoring in chronic
hemodialysis patients, daily home BPs in 20 patients undergoing chronic
hemodialysis were compared with the 44-hour interdialytic ambulatory BPs (ABPs).
Each patient recorded home BPs for 2 consecutive weeks with a digital BP monitor
three times daily. Prehemodialysis and posthemodialysis BPs were recorded by an
oscillometric device in the hemodialysis unit during the same 2 weeks. ABPs were
recorded either after the first or second hemodialysis session of the second week
during a 44-hour interdialytic period using a Spacelab 90207 ABP monitor. ABP
monitoring showed that BP decreased progressively after dialysis, decreased
during the first night, and rapidly reached predialysis levels by the next
morning. There was no decrease in BP during the second night. There was an
excellent correlation between average systolic and diastolic ABP and respective
home BPs. Prehemodialysis diastolic BPs were a good reflection of diastolic ABP,
but there was more variability in predialysis systolic BP. Posthemodialysis BPs
did not correlate with ABP. In patients undergoing chronic hemodialysis, home BPs
more reliably reflected the overall BP than incenter BP readings. Predialysis,
but not postdialysis, BP should be used as a screening tool to detect
hypertension in the hemodialysis unit. Home BP monitoring should be used as a
cost-effective means to diagnose occult hypertension in chronic hemodialysis
patients.
PMID- 10196010
TI - Failure of advance care planning to elicit patients' preferences for withdrawal
from dialysis.
AB - Although withdrawal from dialysis is relatively common among dialysis patients,
little is known about the patients' consideration of withdrawal during advance
care planning. We studied a stratified random sample of 400 hemodialysis patients
in two geographic areas (all six dialysis units within 75 miles of Morgantown,
WV, and all nine dialysis units in Rochester, NY) by reviewing responses to a
questionnaire addressing issues of advance care planning. Interviews were
performed by trained interviewers during a routine hemodialysis treatment. Fifty
one percent of the patients had completed an advance directive (29% had a living
will and a health care proxy, 22% had a living will or proxy). Patients who had
completed advance directives were more likely to have notified their decision
makers of their roles (91% with a living will and health care proxy, 81% with a
living will or proxy v 55% who had no advance directive; P < 0.01). Most patients
had not discussed their wishes for specific interventions in the event of
permanent coma: 41% had discussed mechanical ventilation; 35%, tube feedings;
25%, cardiopulmonary resuscitation; and only 18% had discussed stopping dialysis.
Patients who had completed a living will and proxy were most likely to have
discussed end-of-life care, but stopping dialysis was the least often discussed
intervention, even in this patient subset. Sixty-nine percent had discussed
mechanical ventilation; 55%, tube feedings; 43%, cardiopulmonary resuscitation;
and only 31% had discussed stopping dialysis (all P < 0.001). Although withdrawal
from dialysis is relatively common, it is rarely discussed in advance care
planning by dialysis patients. Dialysis unit staff and nephrologists should
address issues involving withdrawal from dialysis with their chronic dialysis
patients.
PMID- 10196011
TI - A comparison of the calcium-free phosphate binder sevelamer hydrochloride with
calcium acetate in the treatment of hyperphosphatemia in hemodialysis patients.
AB - Current phosphate binders used in hemodialysis patients include calcium-based
binders that result in frequent hypercalcemia and aluminum-based binders that
result in total body aluminum accumulation over time. This investigation
describes the use of a calcium- and aluminum-free phosphate-binding polymer in
hemodialysis patients and compares it with a standard calcium-based phosphate
binder. An open-label, randomized, crossover study was performed to evaluate the
safety and effectiveness of sevelamer hydrochloride in controlling
hyperphosphatemia in hemodialysis patients. After a 2-week phosphate binder
washout period, stable hemodialysis patients were administered either sevelamer
or calcium acetate, and the dosages were titrated upward to achieve improved
phosphate control over an 8-week period. After a 2-week washout period, patients
crossed over to the alternate agent for 8 weeks. Eighty-four patients from eight
centers participated in the study. There was a similar decrease in serum
phosphate values over the course of the study with both sevelamer (-2.0 +/- 2.3
mg/dL) and calcium acetate (-2.1 +/- 1.9 mg/dL). Twenty-two percent of patients
developed a serum calcium greater than 11.0 mg/dL while receiving calcium
acetate, versus 5% of patients receiving sevelamer (P < 0.01). The incidence of
hypercalcemia for sevelamer was not different from the incidence of hypercalcemia
during the washout period. Patients treated with sevelamer also sustained a 24%
mean decrease in serum low-density lipoprotein cholesterol levels. Sevelamer was
effective in controlling hyperphosphatemia without resulting in an increase in
the incidence of hypercalcemia seen with calcium acetate. This agent appears
quite effective in the treatment of hyperphosphatemia in hemodialysis patients,
and its usage may be advantageous in the treatment of dialysis patients.
PMID- 10196012
TI - Prevalence of preterminal pulmonary thromboembolism among patients on maintenance
hemodialysis treatment before and after introduction of recombinant
erythropoietin.
AB - The prevalence of pulmonary thromboembolism at autopsy was assessed in a
retrospective study of a cohort of 185 patients undergoing maintenance
hemodialysis treatment who died in the last decade. The overall frequency of
thromboembolism was 12.43% in the dialysis population, which statistically was
significantly less than in a control group of 8,051 nondialysis patients (21.77%;
P = 0.0023). Moreover, pulmonary thromboembolism was less frequently fatal or
contributing to death in the dialysis group than in the control group (P =
0.039). The prevalence of pulmonary thromboembolism in the dialysis group
remained statistically unchanged over the 10-year period and was independent of a
steady increase in the percentage of patients receiving recombinant
erythropoietin therapy and the average hematocrit values. The occurrence of
preterminal pulmonary thromboembolism was associated with a shorter period since
onset of hemodialysis treatment and with infection as cause of death (P = 0. 031;
P = 0.029, respectively). No statistically significant influence of the type of
basic renal disease, type of dialysis anticoagulation, or dialysis access could
be found. Our data suggest that, at least in the preterminal stage, the
introduction of recombinant erythropoietin within the last decade had no
substantial influence on the prevalence of pulmonary thromboembolism.
PMID- 10196013
TI - Double-blind, placebo-controlled study of growth hormone treatment in elderly
patients undergoing chronic hemodialysis: anabolic effect and functional
improvement.
AB - Elderly patients with end-stage renal disease often have protein and/or caloric
malnutrition that severely affects general well-being and mortality. Uremia is
associated with resistance to the action of growth hormone (GH). This resistance
could be of clinical importance in elderly dialysis patients. In the present
study, the effects of GH treatment were assessed in elderly patients receiving
chronic hemodialysis. Twenty hemodialysis patients with a mean age of 71.7 years
(range, 53 to 92 years) were included on a 6-month, randomized, double-blind,
placebo-controlled trial of GH treatment. The dose of GH was 66.7 microgram/kg,
administered subcutaneously three times weekly immediately after each dialysis
session. Body composition was measured using total-body potassium levels,
computed tomography of the lower leg, and bioelectrical impedance analysis. Serum
albumin concentrations and handgrip strength were also measured. GH treatment
increased the serum concentration of insulin-like growth factor-I (IGF-I), IGF
I/IGF-binding protein-3 ratio, fat-free mass, and the serum concentration of
albumin compared with placebo. The number of patients with serum albumin levels
less than 40 g/L was reduced by a factor of three in the GH-treated group.
Handgrip strength increased in response to GH treatment compared with placebo.
Six months of GH treatment in elderly hemodialysis patients produced anabolic
effects, with improved muscle performance. Also, the number of patients with low
albumin levels was markedly reduced, indicating improved nutritional status
and/or attenuated catabolism. These are all important beneficial effects for
individual patient outcomes.
PMID- 10196014
TI - An innovative approach to temporary hemodialysis vascular access.
AB - The National Kidney Foundation Dialysis Outcomes Quality Initiative (NKF-DOQI)
has set down explicit and extensive guidelines for temporary and permanent
hemodialysis vascular access. It is now incumbent on the nephrologist to ensure
compliance to these standards. Two of our interventional nephrologists performed
402 central venous access procedures over a 12-month period (November 1996 to
October 1997) to test the hypothesis that increased control over insertion
technique would improve outcome. All but eight of the procedures were
successfully completed, resulting in a failure rate of 2%. The expected serious
procedural complication rate outlined in the NKF-DOQI standards is 2%. Our
complication rate was 0.7% if all procedures were accounted for and 0.89% for
just internal jugular and subclavian catheters. We conclude that the use of
interventionally trained nephrologists and strict control of technique can
improve outcome in temporary vascular access procedures.
PMID- 10196015
TI - Ultrasonography of the catheter tunnel in peritoneal dialysis patients: what are
the indications?
AB - The importance of sonography for the early detection and follow-up of tunnel
infections in peritoneal dialysis patients is well documented, whereas other
indications are less clear. We investigated indications and outcome of 738
ultrasound examinations of the peritoneal dialysis catheter tunnel. Indications
for tunnel sonography included routine screening (27%), exit-site infection
without peritonitis (24.1%), follow-up of tunnel infection (29.5%), clarification
of questionable results (7.5%), pain in the course of the catheter tunnel (1.8%),
peritonitis without (5.3%) and with (2.0%) exit-site infection, search for foci
(2.2%), and recurrent peritonitis (0.7%). No positive sonographic results were
obtained during routine screening or in patients with fever or elevated C
reactive protein levels showing no clinical signs of exit-site infection.
Sonographic examinations were positive in 1 of 13 patients with pain in the
course of the catheter tunnel, in 1 of 39 cases of peritonitis not associated
with exit-site infection, in 12 of 15 patients with peritonitis and simultaneous
exit-site infection, and in 2 of 5 patients with recurrent peritonitis.
Questionable results were detected in 15 of 178 patients with exit-site
infection, in 15 of 199 routine examinations, in 2 of 16 examinations of patients
with elevated C-reactive protein levels or fever, and in 2 of 15 cases of
peritonitis and simultaneous exit-site infection. All but two of these
questionable results had to be rated as negative during further follow-up. We
conclude that tunnel sonography is indicated in patients with exit-site infection
(including cases with simultaneous peritonitis), for follow-up of tunnel
infections, and for estimating the prognosis of these infections. Furthermore,
tunnel sonography should be performed in patients with recurrent peritonitis.
Tunnel sonography is not indicated for routine screening, search for foci, in
cases of peritonitis without exit-site infection, or in patients with pain in the
course of the catheter tunnel showing no other clinical signs of exit-site
infection.
PMID- 10196016
TI - Delayed referral of black, Hispanic, and older patients with chronic renal
failure.
AB - Delayed referral (defined as a serum creatinine concentration > 4 mg/dL at
referral) of patients with chronic renal failure to the nephrologist is common in
the United States. We retrospectively examined the records of 220 consecutive
patients referred to an urban teaching hospital nephrology division for
evaluation of chronic renal failure from January 1987 to December 1994 to detect
any relationship between race, renal diagnosis, or age and the timing of referral
of medically-insured patients with chronic renal failure. We documented serum
creatinine concentration and hematocrit at referral, length of time under the
care of a nephrologist (interval from referral to initiation of dialysis), and
total number of clinic visits. The 220 study subjects (120 women, 100 men)
included 139 blacks (63%), 61 whites (28%), 16 Hispanics (7%), and 4 Asians (2%)
aged 51.7 +/- 1.06 years (mean +/- standard error of the mean) at referral. At
referral, nonwhites (black and Hispanic patients) had a greater mean serum
creatinine concentration than whites (4.3 +/- 0.38 v 3 +/- 0.24 mg/dL; P =
0.001), as well as a lower mean hematocrit (31.7% +/- 1.3% v 34.7% +/- 0.9%; P =
0.001). Mean length of time under the care of a nephrologist was shorter in
nonwhites (13 +/- 0.8 months) than whites (43.5 +/- 4.8 months; P = 0.001).
Delayed referral was almost six times more likely in nonwhites than whites (odds
ratio, 5.6; 95% confidence interval [CI], 1.52 to 20; P = 0.008) and five times
more likely in those aged older than 55 years than in those 55 years or younger
(odds ratio, 4. 7; 95% CI, 1.37 to 16; P = 0.01). The greater the serum
creatinine concentration at referral, the greater the odds of receiving less than
12 months of nephrologic care before initiation of dialysis (odds ratio, 1.8; 95%
CI, 1.04 to 3.13; P = 0.03). We conclude that even among those patients with
health insurance, delayed referral to the nephrologist is more likely in black,
Hispanic, and older patients with chronic renal failure than in their white or
younger counterparts.
PMID- 10196017
TI - Hantavirus-specific IgG, IgM, and IgA in acute and chronic renal disease versus
congenital renal disease in the United States.
AB - In a blinded fashion, 165 serum samples from patients with biopsy-characterized
acute and chronic renal diseases (ACRDs), 34 serum samples from patients with
congenital renal diseases (CRDs), and 100 serum samples from healthy adults were
assayed for immunoglobulin G (IgG), IgM, and IgA antibodies to Hantaan and
Puumala viruses by enzyme immunoassay (EIA). Twenty-six percent (44 of 165) of
ACRDs, 3% (1 of 34) of CRDs, and none (0 of 100) of the healthy serum samples
were positive for hantavirus-specific antibodies (P < 0.001, Fisher's exact
test). Thirty of 44 positive serum samples (68%) were from three groups: ie,
acute tubulointerstitial nephritis (AIN), 20% (9 of 44); necrotizing
glomerulonephritis (NG), 27% (12 of 44); and IgA nephropathy, 20% (9 of 44). The
remaining 14 positive samples were from patients with a varied group of renal
conditions. IgA antibody levels alone were elevated in 37%, IgG alone in 33%, IgM
alone in 17%, and all three isotypes in 13% of the AIN-, NG-, and IgA-positive
samples. These data indicate that three renal diseases account for approximately
68% of the hantavirus-positive sera tested and that serological evaluations
should include all three isotypes of antibodies.
PMID- 10196018
TI - Risk factors for IgA nephropathy: a case-control study in Japan.
AB - To disclose the risk factors for immunoglobulin A nephropathy (IgAN), we
conducted a case-control study in the Tokai area of central Japan. The subjects
were 94 patients, aged 20 years or older at diagnosis, who had histologically
confirmed IgAN. Two sex-, age-, and residence-matched controls were randomly
selected for each case from the general population. Information on medical
history and lifestyle was collected using a self-administered questionnaire. The
strength of association between IgAN and a potential risk factor was assessed by
calculating an odds ratio. A family history of chronic nephritis, susceptibility
to the common cold, preference for salty foods, frequent consumption of raw eggs,
and a high intake of carbohydrates, including rice, were significantly associated
with an increased risk for IgAN. Alcohol consumption, use of antioxidant vitamin
supplements, and a high intake of protein, fat, monounsaturated fatty acids, and
all/n-3 polyunsaturated fatty acids were somewhat protective against IgAN.
Episodes of tonsillitis and exposure to organic solvents were found not to be
associated with the risk in the present study. Our findings may provide some
clues to the cause of IgAN.
PMID- 10196019
TI - Renoprotection by nitric oxide donor and lisinopril in the remnant kidney model.
AB - Previous studies showed a renoprotective effect of l-arginine in experimental
uremia. Whether this was caused by an increased nitric oxide (NO) release or
depended on l-arginine per se is not clear. Here, we evaluated whether chronic
administration of an NO donor, molsidomine, controlled systemic blood pressure
and renal disease progression and prolonged survival in rats with renal mass
reduction (RMR). Rats with RMR received the following daily in the drinking
water: group 1 (n = 21), no specific therapy (vehicle); group 2 (n = 12),
molsidomine, 120 mg/L; group 3 (n = 9), lisinopril, 25 mg/L; and group 4 (n =
12), reserpine, 5 mg/L, hydralazine, 80 mg/L, and hydrochlorothiazide, 25 mg/L,
from day 21 after surgery, when rats had hypertension and proteinuria, until the
death of the vehicle-treated rats. Molsidomine normalized systemic hypertension,
only partially reduced proteinuria and serum creatinine levels, but significantly
prolonged animal survival, particularly in the early stage of the disease.
Lisinopril at a similar systemic blood pressure was even better than molsidomine
in limiting proteinuria, preserving renal function, and prolonging survival, but
triple therapy, despite being effective on blood pressure, offered no
renoprotection or prolonged survival. Endothelin-1 (ET-1) levels, formed in
excessive amounts by the kidneys of these animals, were reduced by molsidomine
and lisinopril, but not by triple therapy. The prolongation of survival by NO
donor could be attributed to its effect of reducing ET levels, which in turn may
limit the smooth muscle cell proliferation and matrix accumulation responsible
for organ and, especially, myocardial fibrosis in uremia.
PMID- 10196020
TI - Use of contrast-enhanced computed tomography to measure clearance per unit renal
volume: a novel measurement of renal function and fractional vascular volume.
AB - The iodinated contrast agents used for computed tomography (CT) have
pharmacokinetics similar to inulin and can measure physiological indices, such as
clearance per unit renal volume (alpha/V) and fractional vascular volume (fvv).
Clinical experience with these techniques is, however, scanty, and the present
study explored their potential in subjects with and without renal dysfunction. In
a series of subjects, a single slice of kidney was scanned sequentially after the
bolus injection of contrast material. Time-attenuation curves were constructed,
and alpha/V and fvv were calculated using a Patlak graphic analysis. In the first
part of the study, 50 normal kidneys in 35 subjects (aged 21 to 75 years) were
studied. In the second stage, alpha/V was compared with glomerular filtration
rate (GFR) measurements in 24 patients with diabetes (aged 28 to 84 years) with
or without renal dysfunction. In normal kidneys, alpha/V averaged 0.49 +/- 0.11
mL/min/mL and fvv averaged 35% +/- 12%. These values agree with literature data
obtained using other techniques. A negative correlation was seen between age and
alpha/V (r = 0.66; P < 0.0001), but not fvv. In patients with diabetes, a strong
correlation was observed between renal clearance values, calculated from CT and
corrected for renal volume, and GFR (r = 0.87; P < 0.0001). Dynamic CT can
provide quantitative renal physiological information on a regional basis
noninvasively.
PMID- 10196021
TI - Calcium oxalate nephrolithiasis: effect of renal crystal deposition on the
cellular composition of the renal interstitium.
AB - Urinary calcium oxalate (CaOx) crystals and crystal agglomerates are normally
harmlessly excreted, but in nephrolithiasis they are retained by tubular
epithelial cells and shifted into the renal interstitium. This crystalline
material induces an inflammatory response consisting of an increase in the number
of interstitial cells and an expansion of the extracellular matrix. The newly
arrived cells either derive from the blood or the connective tissue or they are
formed by local proliferation. Identification of the cells that surround the
interstitial crystals is a first step in investigating the question of whether
the interstitial cells could remove the crystalline material. Therefore, we
performed an immunohistochemical study on the kidneys of rats made hyperoxaluric
by ethylene glycol (EG) and ammonium chloride (AC). Attention was paid to
expression of the leukocyte common antigen (LCA), which identifies all types of
leukocytes, the ED1 antigen, which is specific for monocytes and macrophages, and
the major histocompatibility class II antigen (MHC II), which is present on
dendritic cells, B lymphocytes, and activated macrophages. The results obtained
were compared with those seen in two human kidney specimens with acute and
chronic oxalosis. In both rat and humans, macrophages and multinucleated giant
cells are the major cells that encapsulate the interstitial crystals. This
similarity in response underlines the relevance of the rat nephrolithiasis model.
The rat experiments showed, furthermore, that the number of interstitial crystals
and the amount of biochemically measured kidney-associated oxalate both decrease
with time, if the nephrolithiatic agents EG and AC are omitted from the drinking
water. Further studies must clarify whether macrophages and multinucleated giant
cells are able to remove the interstitial crystals and how these cells are
recruited at the inflammatory site.
PMID- 10196022
TI - Increased urinary levels of adrenomedullin in patients with cystitis.
AB - In this study, we examined urinary levels of adrenomedullin (AM) in 18 healthy
volunteers and 18 patients with cystitis. We also compared urinary levels of AM
in 11 patients with cystitis before and after antibiotic treatment. Urinary AM
concentrations were measured by a radioimmunoassay specific for human AM. Urinary
AM levels in patients with cystitis were significantly elevated compared with
those of healthy volunteers and correlated positively with the number of urine
leukocytes. By antibiotic treatment, urinary AM levels significantly decreased as
compared with before the treatment. By RNA blot analysis of AM transcript, we
detected significant levels of AM mRNA in canine urinary bladder and ureter.
Intravenous administration of lipopolysaccharide elevated the AM mRNA level in
the urinary bladder. These data suggest that infection and inflammation stimulate
AM production in the urinary tract, which results in increased urinary AM levels
in patients with cystitis. Based on these results, it is deduced that AM
participates in the pathophysiology of cystitis, and its urinary level could be
used as an index of the degree of cystitis.
PMID- 10196023
TI - Recombinant human growth hormone and Gitelman's syndrome.
AB - Gitelman's syndrome is a primary renal tubular disorder with hypokalemic
metabolic alkalosis, hypocalciuria, and magnesium deficiency. Short stature is
one of clinical manifestations in children. The pathogenesis of short stature in
Gitelman's syndrome is not known. To evaluate whether growth hormone (GH) is
deficient and whether recombinant human GH (rhGH) improves growth rate, rhGH
therapy was tried in a child with Gitelman's syndrome. Both height and body
weight were less than the third percentile. Laboratory and radiologic findings
suggested GH deficiency. During the first 6 months, rhGH therapy with potassium
supplement markedly elevated growth rate from 3.8 cm/yr to 12.0 cm/yr. After
cessation of rhGH, height increment markedly decreased to the pretreatment level
of 3.6 cm/yr during the second 6 months. Additionally, hypomagnesemia was
corrected after rhGH therapy. Accordingly, GH deficiency may contribute to short
stature in children with Gitelman's syndrome, and rhGH therapy would be an
excellent adjunctive treatment for short children with Gitelman's syndrome whose
condition is resistant to conventional therapies in terms of growth.
PMID- 10196024
TI - Acute hyperkalemia associated with intravenous epsilon-aminocaproic acid therapy.
AB - Epsilon-aminocaproic acid (Amicar) is used to treat severe hemorrhage refractory
to usual medical management. This antifibrinolytic drug has been associated with
a number of renal complications. However, there are no descriptions of this
medication causing hyperkalemia. This report describes the development of
hyperkalemia in a patient with underlying chronic renal insufficiency treated
with intravenous epsilon-aminocaproic acid. The patient, who underwent coronary
artery bypass grafting, had no other obvious cause for the acute increase in
serum potassium concentration. Based on data in animals and humans, the cationic
amino acids lysine and arginine have been shown to enter muscle cells in exchange
for potassium and lead to hyperkalemia through a shift of potassium from the
intracellular to the extracellular space. Epsilon-aminocaproic acid, a synthetic
amino acid structurally similar to lysine and arginine, also has been noted to
cause an acute increase in serum potassium in anephric dogs infused with this
medication. It is probable that the mechanism underlying the increase in serum
potassium with epsilon-aminocaproic acid is also based on the shift of potassium
from the intracellular to the extracellular space. Hence, it appears that
intravenous epsilon-aminocaproic acid can also cause hyperkalemia in humans.
PMID- 10196025
TI - Successful treatment of valproic acid overdose with hemodialysis.
AB - A 43-year-old woman took a large amount of depakote (divalproex, a slow-release
form of valproate), became comatose, and developed severe hypotension refractory
to fluid resuscitation and high-dose vasopressors. The serum valproic acid (VPA)
concentration on admission was 1,380 microgram/mL (therapeutic range, 50 to 100
microgram/mL). She also had metabolic acidosis, thrombocytopenia, and normal
renal and liver functions. Hemodialysis was initiated 4 hours after presentation.
After 6 hours of hemodialysis with a high-flux dialyzer, her serum VPA
concentration decreased from 940 microgram/mL to 164 microgram/mL, coincident
with improvement in clinical status. The half-life of VPA was reduced to 2.4
hours with hemodialysis, whereas it was 7.2 hours before the procedure.
Hemodialysis could be a valuable therapeutic intervention in VPA toxicity.
PMID- 10196026
TI - Meropenem pharmacokinetics in a patient with multiorgan failure from
Meningococcemia undergoing continuous venovenous hemodiafiltration.
AB - Meropenem is a carbapenem antibiotic with a broad antibacterial spectrum of
activity. Its main route of elimination is through the kidneys, with 63% of the
drug excreted unchanged in the urine. Meropenem clearance is diminished in renal
impairment; therefore, doses need to be adjusted in patients with varying degrees
of renal function. An appropriate dose of meropenem for patients undergoing
continuous venovenous hemodiafiltration (CVVHDF) is unknown. We evaluated the
pharmacokinetics of meropenem in a patient with fulminant meningococcemia
undergoing CVVHDF. Meropenem concentrations in serial venous, arterial, and
ultrafiltrate samples after a 1 g intravenous dose were measured using high
performance liquid chromatography (HPLC). Meropenem clearance was found to be
129.36 mL/min and 141.29 mL/min for every 8- and 12-hour dosing, respectively.
Trough levels were above the MIC90 for Neisseria meningitidis and most anaerobic
pathogens. We recommend that meropenem 1 g intravenously every 12 hours be used
as the initial dose in patients undergoing CVVHDF. Differences between meropenem
clearance during CVVHDF and other forms of renal replacement therapy are
discussed.
PMID- 10196027
TI - Are physicians assistants the answer to a shortage of nephrologists?
PMID- 10196028
TI - Nephrology workforce shortfall: solutions are needed.
PMID- 10196029
TI - Collapsing glomerulopathy: expanding interest in a shrinking tuft.
PMID- 10196030
TI - Using enhanced computed tomography to measure renal function and fractional
vascular volume.
PMID- 10196031
TI - Cigarette smoking and renal function impairment.
PMID- 10196033
TI - Serotonin and the regulation of renal blood flow in acute renal failure
PMID- 10196032
TI - Hematuria, proteinuria, hypertension, and renal failure in a 10-year-old boy.
PMID- 10196034
TI - MPO-ANCA-Positive crescentic glomerulonephritis: a distinct entity of scleroderma
renal disease?
AB - Scleroderma renal crisis is characterized by intimal thickening of the afferent
glomerular arterioles resulting in hypertension and fibrinoid necrosis of the
capillary tuff. We report a 67-year-old man with long-standing systemic sclerosis
who developed normotensive progressive renal failure, proteinuria, and a
nephritic urinary sediment with serum myeloperoxidase-antineutrophil
cytoplasmatic antibodies (MPO-ANCA). Renal biopsy showed pauci-immune crescentic
glomerulonephritis but none of the typical vascular changes of scleroderma renal
crisis. Because comparable cases have recently been reported from Japan,
normotensive MPO-ANCA-positive crescentic glomerulonephritis may form an entity
of progressive renal failure in scleroderma.
PMID- 10196035
TI - Ask-Upmark kidney associated with renal and extrarenal arterial aneurysms.
AB - Reports of Ask-Upmark kidney, initially described as a congenital defect in renal
development, are uncommon. We report a case with the features of bilateral
asymmetrical segmental atrophy in a patient with childhood-onset hypertension. As
an adult, she developed cerebral, celiac, and renal artery aneurysms. She
underwent successful clipping of the cerebral aneurysm and renal artery repair
with preservation of renal function. Novel radiologic techniques make possible
the noninvasive diagnosis of segmental atrophy and its complications.
PMID- 10196037
TI - Pneumoperitoneum caused by a perforated peptic ulcer in a peritoneal dialysis
patient: difficulty in diagnosis.
AB - Peritonitis due to viscus perforation in peritoneal dialysis (PD) patients can be
catastrophic. We describe the first reported case of perforated peptic ulcer
(PPU) in a PD patient. This 78-year-old man presented with a 1-day history of
mild abdominal pain. He had been receiving nocturnal intermittent PD for 2 years
and had ischemic heart disease and cirrhosis of the liver. Pneumoperitoneum and
peritonitis were documented, but the symptoms were mild. The "board-like abdomen"
sign was not noted. Air inflation and contrast radiography indicated a
perforation in the upper gastrointestinal tract, and laparotomy disclosed a
perforation in the prepyloric great curvature. Unfortunately, the patient died
during surgery. This case illustrates that the "board-like abdomen" sign may be
absent in PD patients with PPU because of dilution of gastric acid by the
dialysate. Free air in the abdomen, although suggestive of PPU, is also not
uncommon in PD patients without viscus perforation. Because PD has to be
discontinued after laparotomy and exploratory laparotomy may be fatal in high
risk patients, other diagnostic methods should be used to confirm viscus
perforation before surgery. PPU, which can be proved by air inflation and
contrast radiography, should be suspected in PD patients with pneumoperitoneum
and peritonitis.
PMID- 10196036
TI - Steroid-responsive pleuropericarditis and livedo reticularis in an unusual case
of adult-onset primary hyperoxaluria.
AB - We present a case of a 54-year-old woman with rapidly progressive renal failure
of uncertain origin, who developed pleuropericarditis and livedo reticularis 6
weeks after initiation of hemodialysis (HD). The presentation with acute renal
failure, the development of serositis, and the dramatic clinical response to
empiric steroid therapy initially suggested the diagnosis of a systemic
inflammatory disorder or vasculitis. Renal biopsy, performed 3 days after
presentation, suggested crystal deposition disease, and subsequent
investigations, using both dialysate oxalate concentrations and liver biopsy, led
to the diagnosis of primary hyperoxaluria (PH). We discuss this atypical adult
presentation of PH and propose a role for the use of steroids in the management
of the acute inflammatory symptoms of oxalosis. We also briefly discuss the
current medical management of patients with PH, including transplantation.
PMID- 10196038
TI - Recurrence of scleroderma in a renal allograft from an identical twin sister.
AB - A patient with scleroderma developed renal failure secondary to recurrence of
scleroderma in a renal allograft from an identical twin. This report reviews the
previous reports of scleroderma recurrence in renal allografts; the differential
diagnosis of scleroderma renal crisis, including cyclosporine toxicity, malignant
hypertension, and allograft rejection; and the pathophysiology of this disease.
PMID- 10196040
TI - Human evolutionary psychology and animal behaviour.
AB - Homo sapiens is increasingly being studied within the evolutionary
(adaptationist, selectionist) framework favoured by animal behaviour researchers.
There are various labels for such work, including evolutionary psychology, human
behavioural ecology and human sociobiology. Collectively, we call these areas
'human evolutionary psychology' (HEP) because their shared objective is an
evolutionary understanding of human information processing and decision making.
Sexual selection and sex differences have been especially prominent in recent HEP
research, but many other topics have been addressed, including parent-offspring
relations, reciprocity and exploitation, foraging strategies and spatial
cognition. Many HEP researchers began their scientific careers in animal
behaviour, and in many ways, HEP research is scarcely distinguishable from other
animal behaviour research. Currently controversial issues in HEP, such as the
explanation(s) for observed levels of heritable diversity, the kinds of data
needed to test adaptationist hypotheses, and the characterization of a species
typical 'environment of evolutionary adaptedness', are issues in animal behaviour
as well. What gives HEP a distinct methodological flavour is that the research
animal can talk, an ability that has both advantages and pitfalls for
researchers. The proper use of self-reports and other verbal data in HEP might
usefully become a subject of future research in its own right. Copyright 1999 The
Association for the Study of Animal Behaviour.
PMID- 10196039
TI - Unexpected severe hypocalcemia during continuous venovenous hemodialysis with
regional citrate anticoagulation.
AB - Citrate is known to induce acute hypocalcemia in patients undergoing liver
transplantation during the anhepatic phase. We describe the case of a 71-year-old
woman with fulminant hepatic failure secondary to hepatitis A, who was started on
continuous venovenous hemodialysis (CVVHD) for acute renal failure. Because
anticoagulation with heparin was untenable, regional anticoagulation was
accomplished by trisodium citrate (46.7%) infusion. Unfortunately, severe
hypocalcemia developed when citrate accumulated because of impaired hepatic
metabolism. Because of chelation by citrate, the ionized calcium concentration
declined to values as low as 2.72 mg/dL (normal, 4.5 to 5.6 mg/dL), whereas the
total calcium concentration remained in the normal range. With an unusually high
calcium chloride infusion rate via a central line (up to 140 mL/h of 10 mEq/dL
CaCl2) and additional boli of CaCl2 (for a total of 190 mEq), the ionized calcium
concentration could be maintained at target levels. Nevertheless, the ionized
calcium concentration was maintained in the normal range, and the total calcium
concentration increased to a value as high as 15 mg/dL. Thus, the total to
ionized calcium ratio was 3.5:1. After 24 hours of treatment, trisodium citrate
infusion was gradually reduced from 15 mL/h to 7 mL/h, and the calcium chloride
infusion was decreased to 50 mL/h. Nevertheless, persistence of the elevated
total to ionized calcium ratio (3:1) indicated citrate accumulation likely
secondary to decreased hepatic metabolism. Using this approach, the patient was
successfully maintained on CVVHD with regional citrate anticoagulation for a
total of 11 days without any additional complications. We conclude that CVVHD
with regional citrate anticoagulation can be used in patients with acute hepatic
failure if increased CaCl2 requirements are anticipated and if citrate is infused
at a lower rate compatible with decreased citrate metabolism. Citrate
accumulation should be suspected in patients with an elevated total to ionized
Ca++ ratio during CVVHD with citrate anticoagulation.
PMID- 10196041
TI - Experimental evidence for mutual inter- and intrasexual selection favouring a
crested auklet ornament.
AB - During the breeding season, female and male crested auklets Aethia cristatella
(Alcidae), display similar conspicuous crest ornaments composed of elongated
forward-curving feathers on their foreheads. Based on quantifications of brief
agonistic interactions at a large breeding colony, we found that crest length was
strongly correlated with dominance within both sexes. Across the full range of
crest length, individuals with longer crests were dominant over shorter-crested
individuals in agonistic interactions involving same-sex adults. Within subadults
(2-year-olds of unknown sex), there was a similar trend towards longer-crested
individuals being dominant. In agonistic interactions involving individuals of
different sex and age, adult males were dominant over adult females and adults
were dominant over subadults, regardless of crest length. In an experiment in
which we manipulated crest length using life-size realistic models, male auklets
that responded were less aggressive to male models with longer crests than to
models with normal or shorter crests, confirming that crest length by itself
signals dominance status. In a related experiment in which we controlled
intrasexual competition, both males and females responded to opposite-sex models
with more frequent sexual displays when the models had long crests compared with
those having short crests, suggesting that crested auklets also have mating
preferences that favour long crest ornaments. Taken together, these results
support the idea that the crest ornament is favoured by both intra- and
intersexual selection. Copyright 1999 The Association for the Study of Animal
Behaviour.
PMID- 10196042
TI - Acoustic interference limits call detection in a Neotropical frog Hyla ebraccata.
AB - Problems1999 The Association for the Study of Animal Behaviourassociated with
communication in noisy environments include detection, discrimination, and
localization of appropriate signals. I investigated the effects of broadband
background noise on call detection by female Copyright 1999 The Association for
the Study of Animal Behaviour.
PMID- 10196043
TI - The cost of peripheral males in a brook trout mating system.
AB - A focus on the reproductive contributions of males displaying alternative life
histories has neglected the role of size-dependent peripheral males in salmonine
mating systems. We documented mating behaviour of brook trout Salvelinus
fontinalis, including observations of spawning, over two breeding seasons to
determine the mating costs of peripheral males to dominant males (kleptogamy) and
females (egg cannibalism). For males and females, the mating costs of peripheral
males were substantial because more than half (56%) of all observed brook trout
spawnings involved peripheral males. Males that paired with large females
experienced a greater incidence of kleptogamy due to increased numbers of
peripheral males present. Large males face a conflict when mating in that they
prefer to spawn with large females; however, these same females attract numerous
males against which the dominant male cannot defend. From paternity studies, we
estimated that males that had peripheral males participate in spawning may
fertilize, on average, equal numbers of eggs compared to males spawning solely
with a smaller female. Females that paired with relatively smaller males had
significantly more eggs eaten by peripheral males than females that paired with
relatively larger males. Latency to spawn by females increased when paired with a
relatively small male, and resulted in females obtaining a larger spawning
partner. The observed patterns of size-assortative mating, kleptogamy and
cannibalism are discussed in relation to mate choice for this population of brook
trout. Copyright 1999 The Association for the Study of Animal Behaviour.
PMID- 10196044
TI - Contextual determinants of female-female mounting in laboratory rats.
AB - Female-female mounting is widespread among mammalian species, but little is known
about the proximal function of this behaviour. While such mounting is often
regarded as a 'masculine' trait, its widespread occurrence may indicate that it
serves specific functions within the context of female-female social behaviour.
We valuated female mounting behaviour in Long-Evans rats in standard observation
chambers and in a seminatural enclosure. Under these conditions, we examined a
number of potential factors that might influence mounting, including the oestrous
cycle, social hierarchy, familiarity and male presence. The female's mounting was
not influenced by her own oestrous cycle, but did vary with the oestrous cycle of
the stimulus female. Socially dominant females mounted significantly more than
subordinate females, and mounting by the dominant female was most frequent when
the subordinate female was sexually receptive. Females mounted (and fought with)
unfamiliar females significantly more than they did with familiar cagemates.
Female-female mounting was dramatically reduced when males were present. Further
testing showed that female mounting did not affect the induction of the
progestational state of pregnancy, suggesting that female mounting does not
function as a pseudomale behaviour that can substitute for genital stimulation
provided by the male. Based on these data, female mounting does not appear to
function as a sexual behaviour per se, but may serve as a form of female social
behaviour related to maintenance of the female's social status within female
groups. In this regard, the results of this study suggest that female mounting is
part of the normal female's complex behavioural repertoire and does not
necessarily reflect masculinization of some underlying neural substrate.
Copyright 1999 The Association for the Study of Animal Behaviour.
PMID- 10196045
TI - The role of urine marking in the foraging behaviour of least chipmunks.
AB - Least chipmunks Tamias minimus, occasionally deposit urine on buried patches of
seeds after sampling the patch, a behaviour never before reported for rodents.
The results of these experiments show that (1) patch-marking is a deliberate act,
bearing no resemblance to routine excretion, (2) marking deters both the marker
and conspecifics from harvesting attempts, (3) chipmunks can discriminate their
own marks from those of others, and (4) the incidence of marking in the wild is
at least as frequent, and its deterrent effect as strong as in the laboratory.
Although the message conveyed by a mark is clearly exploited by conspecifics, and
may benefit kin, the results accord best with prevailing theory advanced for
canids, that an olfactory reminder of patch value improves the marker's foraging
efficiency. Copyright 1999 The Association for the Study of Animal Behaviour.
PMID- 10196046
TI - Problem solving and functional design features: experiments on cotton-top
tamarins, Saguinus oedipus oedipus.
AB - In any problem-solving situation, there are features associated with the problem
that are relevant from a functional perspective and other features that are
irrelevant. To determine whether animals are sensitive to the distinction between
functionally relevant and irrelvant features of a problem, we conducted two main
experiments with a New World monkey, the cotton-top tamarin. In the first
condition of both experiments, subjects were required to pull a piece of cloth to
gain access to a piece of food. The first experiment involved choosing between
food that was on the cloth and food that was off the cloth. The second experiment
involved choosing between food that was on a connected piece of cloth and food
that was on two pieces of cloth separated by a horizontal gap. Having learned to
solve either of these two problems, we conducted a series of probe conditions to
determine whether the tamarins would generalize to changes in the shape, size,
colour, and texture of the cloth and food, the position of the food relative to
the cloth, and the type of connection between two pieces of cloth. For most of
the probe conditions, the tamarins readily generalized, showing no decrement in
performance, even on the first trial. For other conditions, involving apparently
more subtle discrimination (e.g. a narrow vertical gap between the two pieces of
cloth), explicit training was required. These results indicate that tamarins
solve means-end relationships, and that their ability depends on a discrimination
between properties that are functionally relevant as opposed to irrelevant.
Copyright 1999 The Association for the Study of Animal Behaviour.
PMID- 10196047
TI - The meaning and function of grunt variants in baboons.
AB - Wild baboons Papio cynocephalus ursinus, give tonal, harmonically rich
vocalizations, termed grunts, in at least two distinct, behavioural contexts:
when about to embark on a move across an open area ('move' grunts); and when
approaching mothers and attempting to inspect or handle their young infants
('infant' grunts). Grunts in these two contexts elicit different responses from
receivers and appear to be acoustically distinct (Owren et al. 1997 Journal of
the Acoustical Society of America101 2951-2963). Differences in responses to
grunts in the two contexts may, then, be due to acoustic differences, reflecting
at least a rudimentary capacity for referential signalling. Alternatively,
responses may differ simply due to differences in the contexts in which the
grunts are being produced. We conducted playback experiments to test between
these hypotheses. Experiments were designed to control systematically the effects
of both context and acoustic features so as to evaluate the role of each in
determining responses to grunts. In playback trials, subjects differentiated
between putative move and infant grunts. Their responses based only on the
acoustic features of grunts were functionally distinct and mirrored their
behaviour to naturally occurring move and infant grunts. However, subjects'
responses were in some cases also affected by the context in which grunts were
presented, and by an interaction between the context and the acoustic features of
the grunts. Furthermore, responses to grunts were affected by the relative rank
difference between the caller and the subject. These results indicate that baboon
grunts can function in rudimentary referential fashion, but that the context in
which grunts are produced and the social identity of callers can also affect
recipients' responses. Copyright 1999 The Association for the Study of Animal
Behaviour.
PMID- 10196048
TI - Behavioural aspects of the raccoon mating system: determinants of consortship
success.
AB - We monitored raccoons Procyon lotor, in southern Texas during the 1990-1992
mating seasons to describe mating behaviour and identify factors affecting
consortship success. During most of this study, raccoons were spatially
aggregated, with female home ranges congregated around permanent water sources
and larger home ranges of male groups encompassing each female group. Consortship
success varied among males and ranged from zero to six females per male within a
mating season. Individual females consorted with one to four different males
during an oestrous period; however, most (62%) females consorted with only one
male during their oestrus. Dominance through overt conflict appeared to influence
male consortship success. During two mating seasons, one male from each group
consorted with females on more days than all other males combined. Body weight of
males was positively correlated with number of consortship days. As synchrony of
oestrus increased, variance in number of consortship days among males decreased,
and access to oestrous females increased for subordinate males. Wounding among
males increased during the mating season, and was more frequent for males than
for females. The mating system, as determined by consortship behaviour, appeared
to shift between polygyny and promiscuity, and possibly varied annually as a
result of the timing of oestrous cycles. Copyright 1999 The Association for the
Study of Animal Behaviour.
PMID- 10196049
TI - Social interactions unmask sex differences in humoral immunity in voles.
AB - Sex differences in immune function are well established among laboratory rodents,
with males typically having lower immunity than females. This sex difference may
reflect the suppressive effects of testosterone on immune function. Because
polygynous males generally have higher circulating testosterone concentrations
than monogamous males, sex differences in immune function are hypothesized to be
more pronounced among polygynous as compared to monogamous species. Sex
differences in immune function have not been consistently observed among
individually housed Microtus in the laboratory; thus, social interactions are
hypothesized to be necessary for the expression of sex differences in immune
function. We assessed the effect of differential housing conditions on humoral
immunity and steroid hormone concentrations in polygynous meadow voles Microtus
pennsylvanicus, and monogamous prairie voles M. ochrogaster. We examined humoral
immunity by immunizing voles with keyhole limpet haemocyanin (KLH) and measuring
antibody production 5, 10, 15 and 30 days postimmunization. Overall, meadow voles
mounted higher anti-KLH immunoglobulin (Ig)M and IgG responses than prairie
voles, regardless of the housing condition. Sex differences in antibody
production were only observed among meadow voles housed in pairs, in which
females had higher anti-KLH IgM and IgG responses than males. Sex differences in
antibody production were not observed among prairie voles or meadow voles housed
individually. Sex and species differences in circulating oestradiol,
testosterone, and corticosterone concentrations were not related to differences
in humoral immunity. These data suggest that sex differences in immune function
are more pronounced among polygynous species than monogamous species, but may be
context dependent. Copyright 1999 The Association for the Study of Animal
Behaviour.
PMID- 10196050
TI - Temporal call changes and prior experience affect graded signalling in the
cricket frog.
AB - We investigated how male cricket frogs Acris crepitans, alter their advertisement
calls in response to broadcasts of synthetic calls that were either 'attractive'
or 'aggressive'. The stimulus calls differed in temporal but not spectral
characteristics. Male cricket frogs produced a more aggressive call when
presented with the aggressive stimulus, indicating that they perceived the
temporal differences between the two call categories. The direction and degree of
temporal and spectral changes depended on the relative dominant frequency of the
resident and opponent. If the resident's dominant frequency was initially higher
than the stimulus frequency, the pattern of change in dominant frequency mirrored
that seen for the temporal call characters. In contrast, if the resident's
initial dominant frequency was below that of the stimulus, then the temporal and
spectral changes were in opposite directions. Furthermore, stimulus order
influenced whether males responded differently to playbacks of aggressive and
attractive calls; males that received the aggressive call first produced more
aggressive calls during the aggressive stimulus, while males that received the
attractive call first produced similar calls in response to the two stimuli. This
suggests that experience with different types of signals influences the
subsequent calling behaviour of male cricket frogs. Copyright 1999 The
Association for the Study of Animal Behaviour.
PMID- 10196051
TI - Variation and consistency of female preferences for simulated courtship songs in
Drosophila virilis.
AB - To study the variation and consistency of song preferences in Drosophila virilis
females, we played them species-specific song and songs with modified sound
pulses and/or interpulse intervals on 3 consecutive days. Species-specific song
was played again on the fourth day. All playbacks were done without the presence
of males. About 62% of the females indicated their readiness to mate by spreading
their wings in at least one of the trials. The proportion of the females
responding to species-specific song was about twice that of the females
responding to modified songs. The majority of females responded to only one song
type, which suggests that the females varied in their preferences and that their
preference windows were rather narrow. The females were consistent in their
responsiveness to species-specific song played on 2 days. If the female responded
to normal song during the first trial, the probability of her responding to the
same song during the second trial increased by about 32%. The number of songs
required by the females before responding in the two subsequent trials was also
correlated within the females (repeatability 0.328). Repeatability of female
preferences for male sexual traits is expected both in the viability and
Fisherian models of sexual selection. Copyright 1999 The Association for the
Study of Animal Behaviour.
PMID- 10196052
TI - Parent-offspring interactions in food provisioning of Manx shearwaters:
implications for nestling obesity.
AB - Procellariiform seabirds such as the Manx shearwater Puffinus puffinus, rear only
one chick at a time but may breed many times in their lives; parents should thus
limit food delivery to the chick in keeping with the balance between current and
future reproductive output. Yet procellariiform chicks accumulate large
quantities of lipid, which may provide a buffer against pronounced and
unpredictable variation in food provisioning, resulting in part from an inability
of parents to regulate food supply to the nest. We switched chicks between nests
to examine the roles of parents and offspring in controlling food delivery. The
serial autocorrelation in age-specific body masses for unmanipulated chicks
decreased from 0.61 (P< 0.01) to 0.35 (NS) over a period of 15 days and remained
nonsignificant thereafter. By contrast, the serial autocorrelation for switched
chicks increased from 0.64 (P< 0.01) to 0.83 (P< 0.001) and the serial cross
correlation rose from 0.23 (NS) to 0.50 (P< 0.05). These results supported both
chick determination and parental determination models of food provisioning,
indicating that chicks conveyed information about their nutritional status, which
parents acted upon by adjusting their rate of food delivery. We discuss these
results in relation to the optimization of nestling lipid reserves and parental
foraging effort. We suggest that information conveyed by the chick's begging
intensity serves to reduce the provisioning rate to well-fed chicks, but parents
cannot or do not increase food provisioning to poorly fed chicks. Such adjustment
of food provisioning does not refute the hypothesis that nestling obesity
provides a buffer against highly variable food delivery. Copyright 1999 The
Association for the Study of Animal Behaviour.
PMID- 10196053
TI - Helping behaviour in facultatively eusocial hover wasps: an experimental test of
the subfertility hypothesis.
AB - A candidate explanation for the evolution of eusociality is that helpers are
physiologically constrained such that helping is their only realistic option. We
tested this subfertility hypothesis in a species of facultatively eusocial hover
wasp (Hymenoptera, Stenogastrinae: Liostenogaster flavolineata) by seeing whether
helpers that were forced to nest on their own were able to mature their own eggs.
One focal helper was left alone on each of 22 nests, from which all other adult
wasps (including the dominant) were permanently removed. After 18 days, all but
one of the 19 focal helpers that remained on their nests had ovarian development
and insemination status characteristic of dominants, and the majority had
probably laid eggs. This was in striking contrast to the reproductive status of
other helpers removed from the same nests at the start of the experiment. These
results provide convincing experimental evidence that females do not become
helpers because of some unconditional physiological constraint. There is
currently no unequivocal support for the subfertility hypothesis in facultatively
eusocial Hymenoptera lacking morphological castes. Copyright 1999 The Association
for the Study of Animal Behaviour.
PMID- 10196054
TI - Yelling for sex: harem males compete for female access in bronze-winged jacanas.
AB - Sperm competition in sex-role reversed, polyandrous jacanas is intense because
females copulate with multiple male mates before laying each clutch. These males
may be unable to attempt to maximize their share of copulations by mate guarding
or forcing copulations. Instead, males in polyandrous harems may compete for
sexual access to the female by giving a call, termed the 'yell', to attract her.
Male bronze-winged jacanas, Metopidius indicus, yelled at higher rates in larger
harems, and when the female was further from the yeller or on a comate's
territory. Half of all yells were given at mating platforms where all copulations
occurred. Males that received the clutch yelled at lower rates during the
incubation and chick care periods. Yells attracted the female when she was far
from the yeller or with a comate. When the yell of a polyandrous male was
broadcast from his territory, the female was more likely to fly to his territory
during playback than during control periods. Within polyandrous harems the males
that yelled at the highest rates received the most copulations, and three out of
four females gave clutches to the male that gave the longest and most frequent
yells, so females may have used yells to assess male quality. Intrusions by
females, but not males, increased during yell playbacks, and tended to be more
frequent on the territories of males with high yell rates. Females may therefore
respond to their mates' yells because yells may attract female intruders which
may attempt to take over the territory. Copyright 1999 The Association for the
Study of Animal Behaviour.
PMID- 10196055
TI - Prospecting enhances breeding success of first-time breeders in the great
cormorant, Phalacrocorax carbo sinensis.
AB - In many species of colonial seabirds, young birds visit colonies in the years
before they start breeding. This prospecting behaviour may allow them to obtain
information that could enhance their future breeding success. We examined the
reproductive consequences of prospecting behaviour in the colonial great
cormorant, and found support for this idea. New breeders that had been
prospecting actively in the previous year obtained breeding sites of higher
quality (i.e. closer to sites where conspecifics had fledged young in the
previous year) and had higher breeding success than those that had been less
active. Prospecting occurred mostly late in the breeding season, and coincided
with the time when the majority of the eggs had hatched but before the chicks
started fledging, that is, when breeding success in the colony reflected habitat
suitability. These results are thus consistent with the use of conspecific
reproductive performance as a cue for the quality of a breeding habitat as
expected from the 'performance-based conspecific attraction hypothesis'.
Copyright 1999 The Association for the Study of Animal Behaviour.
PMID- 10196056
TI - Song type switching in the chaffinch, Fringilla coelebs : timing or counting?
AB - The song of many bird species is relatively constant in form, yet each bird has
more than one song type, making it an excellent model for studies of the
mechanisms underlying switching between behaviour patterns. The chaffinch is a
good example. Males sing with eventual variety, repeating each song type in the
repertoire a few times before switching to another type. The mechanism triggering
these switches is not known. We investigated long continuous recordings of
spontaneous singing by six wild males to test two hypotheses: (1) that a maximum
number of repetitions limits bout length; or (2) that a switch occurs after a
song type bout reaches a maximum duration ('time window'). Strong evidence was
found for a temporal limitation: song type bouts with many repetitions were
delivered only at a fast rate, whereas bouts consisting of few songs were
delivered either fast or slow. Copyright 1999 The Association for the Study of
Animal Behaviour.
PMID- 10196057
TI - Food provisioning to nestling shearwaters: why parental behaviour should be
monitored?
AB - We examined temporal variation in food delivery to nestling Cory's shearwaters
Calonectris diomedea, by repeated periodic weighings during the night. We tested
whether the magnitude and frequency of meals were influenced by the condition of
chicks. In contrast to previous studies of chick provisioning in petrels and
shearwaters, the evidence of feeding derived from chick weight gains was
complemented by data provided by an electronic system, which logged the entry of
each parent to the nest. Estimates of feed size and visiting frequency obtained
from chick weighing alone differed from similar estimates obtained using the
automatic logging equipment. The data obtained with the logging system combined
with chick weighing also showed that, to some extent, food provisioning was
regulated, chicks left in poorer condition being more likely to receive food the
next night than those left in better condition. The methods based on chick weight
gains alone did not detect this regulation effect. Our findings suggest that
resolving parental visits to the nest is crucial to obtain accurate parameter
estimates, and to address the problem of regulation of provisioning rates in
Procellariiformes. Our results do not support the hypothesis that accumulation of
fat is just a by-product of chronic overfeeding arising from stochastic variation
in foraging success at sea. Copyright 1999 The Association for the Study of
Animal Behaviour.
PMID- 10196058
TI - Suckling behaviour does not measure milk intake in horses, Equus caballus.
AB - Studies of parental investment in mammals have frequently used suckling behaviour
to estimate energy transfer from mother to offspring, and consequently to measure
maternal input. Such studies assume that the more an offspring sucks, the more
milk it will receive. This assumption has been questioned, and a review of the
literature found little support for it. To test if suckling behaviour provided an
accurate index of milk or energy intake we used a radioactive isotope technique
to label the milk of thoroughbred mares and to measure milk transfer to foals. We
found no significant linear relationship between usual measures of suckling
behaviour and milk or energy intake. No behaviours associated with suckling nor
with characteristics of mares and foals improved the relationship; only the
number of butts associated with each suck episode even approached significance.
If we had used suckling behaviour to test theories on differential maternal
investment our conclusions would have been in error. For example, female foals
tended to suck for longer than males did but there was no difference in the
amount of milk transferred. Consequently, we show that measures of suckling
behaviour do not adequately predict milk intake in the domestic horse and we
suggest that conclusions about differential maternal investment in mammals based
on suckling behaviour are likely to be in error. Copyright 1999 The Association
for the Study of Animal Behaviour.
PMID- 10196059
TI - Mate choice copying versus preference for actively displaying males by female
pied flycatchers.
AB - Should a female copy the mate choice of other females? A female may rank a mated
male higher in quality than an unmated male because the former has demonstrated
that he is able to attract a female. However, a prospecting female may also avoid
a mated male because of the risk that she has to compete with the male's initial
mate over access to copulations, breeding resources and male parental care. We
studied the mate choice of female pied flycatchers Ficedula hypoleuca, in
aviaries divided into three compartments, two for males, and one for a female. A
female was allowed to choose (build a nest in a nestbox) between two males after
a period when she had been kept in a cage behind a one-way mirror and had
presumably seen that one of the males was in the company of another female for 5
h. There was no evidence that females copied the mate choice of conspecific
females, or that they avoided males that had recently been in the company of
another female. Instead, females apparently chose a mate independently of others,
choosing the male showing most courtship display. The latter result explains the
consistency in mate choice observed when different females chose between the same
pair of males in repeat trials. The ability of females to pick out the same male
independently may also explain why a few males obtain most copulations in lekking
species. Copyright 1999 The Association for the Study of Animal Behaviour.
PMID- 10196060
TI - Cattle egrets are less able to cope with light refraction than are other herons.
AB - The majority of heron species (Aves, Ardeidae) forage on aquatic prey in shallow
water. Prey detection, aiming and the beginning of the capture strikes are
performed while the heron's eyes are above water. For most angles, as a result of
air/water light refraction, the apparent image available to a heron is vertically
displaced from the prey's real position. Herons must therefore correct for
refraction. We tested the hypothesis that species that forage in aquatic habitats
should be more able to correct for image disparity than those of terrestrial
habitats. The ability of hand-reared herons of four species to capture stationary
prey (fish) underwater (submerged) or in air (aerial) was tested. Three species
(little egret Egretta garzetta, squacco heron Ardeola ralloides, and night heron
Nycticorax nycticorax) normally forage in aquatic habitats while the fourth
(cattle egret Bubulcus ibis) forages in terrestrial habitats. No individuals
missed aerial prey. Success rates of little egrets and of squacco herons with
submerged prey were high, while night herons became less successful with
increased prey depth and/or distance. In cattle egrets, success rate was low and
negatively correlated with prey depth. The observed interspecific differences may
thus be related to (1) differential ability to correct for air/water light
refraction and (2) the species' foraging behaviour. We suggest that cattle egrets
are in the process of losing their ability to cope with submerged prey. Copyright
1999 The Association for the Study of Animal Behaviour.
PMID- 10196061
TI - Staying in plastic containers interferes with the orientation of clock-shifted
homing pigeons.
AB - Staying in plastic containers ventilated with natural air during transport and
while waiting at the release site was found to affect the initial orientation of
pigeons, Columba livia f. domestica, that were exposed to a 6-h clock-shift. The
deflection from the mean direction of controls was significantly smaller, and the
mean vector length was significantly shorter, than that of clock-shifted pigeons
transported in conventional wooden cages. This effect was most pronounced when
the birds stayed in plastic containers for the first and second time. Nonshifted
control birds seemed to be largely unaffected by plastic containers. There was no
influence on homing performance, which suggests a transient nature of the effect.
Since the clock-shifted birds had access to the same orientational cues as the
controls, we suggest that their sun compass was impaired by stress. We discuss
general implications of this container effect, particularly in relation to some
cases of olfactory deprivation where containers have been used and stress-induced
side-effects cannot be excluded. Copyright 1999 The Association for the Study of
Animal Behaviour.
PMID- 10196062
TI - Alliances and reproductive success in Camargue stallions.
AB - A study of a herd of Camargue horses Equus caballus, showed that while the
majority of high-ranking stallions held single-male harems, some sons of low
ranking mares, being low ranking themselves, formed alliances that could last a
lifetime. The two stallions were each other's closest associate and preferential
grooming partner. Alliances were based on coalitions in which either both
partners confronted an intruder synchronously or the dominant of the pair tended
the female(s) while the subordinate simultaneously displayed towards the rival.
Alliance partners were of similar age but were not more closely related to each
other than to other stallions in the herd. Long-term paternity data revealed that
subordinates sired close to a quarter of the foals born into the alliance group,
and significantly more foals than low-ranking stallions in the herd adopting a
'sneak'-mating strategy. The dominant appeared to benefit from the presence of
his subordinate partner. Fights occurred all year round, and the subordinate
stallion of each alliance pair fought outside competitors more than twice as
often as the dominant. Forming short-term alliances before defending mares on
their own may enhance long-term reproductive success for both partners. Other
benefits to both partners include higher survivorship of their foals and
increased access to proven reproductive mares. These results suggest that the
relationship between alliance partners is based on mutualism, but several
conditions for reciprocity seem to be fulfilled: the benefit to the dominant
(assistance in fights), and the benefit to the subordinate (access to
reproduction), are both costly to the other partner and delayed in time.
Copyright 1999 The Association for the Study of Animal Behaviour.
PMID- 10196063
TI - The social transmission of spatial information in homing pigeons.
AB - We adapted a technique to explore the social transmission of spatial information
in homing pigeons Columba livia. Five demonstrator pigeons were first trained to
find a food goal within an indoor arena. This arena consisted of nine lidded cups
laid out within a 12x12 grid on the floor. The task was to find the goal cup and
flip the lid to obtain the food hidden within. Once the demonstrators had reached
criterion the experiment proper began. During stage 1 of the experiment, 10
target birds, which had not previously been trained to find the goal, were
introduced to the spatial task either in isolation or paired with a demonstrator.
We measured how long they took to complete the task, the number of squares
crossed on the grid, and the number of incorrect lids flipped. In stage 2, the
target birds were introduced to the arena a second time, by themselves, and we
compared the performance of the birds in the two treatments. The pigeons that had
been introduced to the task with a demonstrator in stage 1 walked further and
made more incorrect choices when searching for the food goal in stage 2 than the
pigeons that were introduced to the task alone. This indicates that pigeons learn
a spatial, food-finding task more effectively when performing the task alone than
when accompanied by a knowledgeable conspecific. We discuss possible reasons for
this in the light of previous experiments. Copyright 1999 The Association for the
Study of Animal Behaviour.
PMID- 10196064
TI - Synchronous polyandry and multiple paternity in the frog Crinia georgiana (Anura:
Myobatrachidae).
AB - Multiple paternity has rarely been reported in anuran amphibians, with only three
previous documented examples. For the Australian frog Crinia georgiana, we
observed synchronous polyandry in an average of 44% of matings observed at four
field sites. This suggests matings involving more than one male are common in
this species. One to eight males were observed in amplectant groups with second
males amplexed ventrally. Genetic analyses, using allozyme electrophoresis, of
offspring from two matings indicated that at least two of three possible males
fathered offspring. Third males were unlikely to have shared paternity, explained
by their inappropriate position during amplexus. Multiple paternity may be more
common in frogs than has been reported. Copyright 1999 The Association for the
Study of Animal Behaviour.
PMID- 10196066
TI - Intraindividual variance in trait size and the analysis of developmental
instability.
PMID- 10196065
TI - Semelparity and the evolution of maternal care in insects.
PMID- 10196067
TI - Book Received.
PMID- 10196068
TI - How do animals 'do' geometry?
PMID- 10196069
TI - How do they, indeed? A reply to Biegler et al.
PMID- 10196070
TI - Human parallel to voluntary wheel running: exercise.
PMID- 10196071
TI - Call for papers
PMID- 10196072
TI - Acknowledgments
PMID- 10196073
TI - Verbal and spatial short-term memory: common sources of developmental change?
AB - Verbal and spatial span, articulation and tapping rate, and verbal and spatial
speed-of-search tasks were administered to sixty 6- to 12-year-olds. A variance
partitioning procedure was then used to identify age-related and age-invariant
components of variance in span. Outcomes were very similar for verbal and spatial
span, in particular, (i) most of the age-related variance was shared by the speed
of-search and rate predictors, (ii) articulation rate provided an age-independent
contribution, (iii) changing-state versions of predictor tasks did not account
for variance over steady-state versions, and (iv) predictors of the same modality
as the span task did not outperform predictors of the other modality. We conclude
that verbal and spatial short-term memory appear to rely on similar processes
when serial recall is required and that developments in span are closely tied to
increases in processing speed.
PMID- 10196074
TI - Memory strength affects reporting of misinformation.
AB - A model of long-term retention was used to examine whether and how the strength
of original information (differences in learning and testing time) and the
strength of misleading information (differences in timing and frequency)
influence 3- to 5-year-olds' memory for an event. In three experiments,
preschoolers viewed a slide presentation depicting an event, some of them were
asked misleading questions, and memory for event details was tested. There was
little evidence of memory impairment, but exposure to misleading information
encouraged reporting of this information. Differences in learning influenced
reporting in that children exposed to the event once reported more misled details
than those who saw the event multiple times. Furthermore, preschoolers who saw
the event once were just as susceptible to misleading information whether exposed
to misinformation once or three times; however, preschoolers who had seen the
event multiple times were susceptible only to repeated presentations of
misinformation. Given that the reporting of misinformation is determined by the
degree of integrity of both the original and misleading information, it is
important to control for differences in trace strength for both types of
information in future research.
PMID- 10196075
TI - Infants' memory processing of a serial list: list length effects.
AB - Six-month-olds, trained with a three-mobile serial list, exhibit a primacy effect
24 h later. In three experiments, we demonstrated that increasing list length
impairs their memory for serial order. In all experiments, 6-month-olds were
trained with a five-mobile list. In Experiment 1, infants failed to exhibit a
primacy effect on a 24-h delayed recognition test, recognizing mobiles from all
serial positions. In Experiment 2, infants did exhibit a primacy effect on a
reactivation (priming) test, suggesting that they may originally have encoded
serial-order information. Experiment 3 confirmed that serial-order information
was represented in infants' training memory. After the reactivation treatment,
infants were precued with one list member and tested for recognition of another.
When precues specified valid order information, infants recognized test mobiles
from the later serial positions. The memory dissociation for serial order on
delayed recognition and reactivation tests adds to the growing evidence that
young infants possess two functionally distinct memory systems.
PMID- 10196076
TI - Mitochondrial DNA phylogeny of West African aplocheiloid killifishes
(Cyprinodontiformes, Aplocheilidae).
AB - African killifishes (Cyprinodontiformes, Aplocheilidae) historically associated
with the genus Aphyosemion occur in two geographically distinct regions. One
assemblage from far West Africa has been previously shown to be monophyletic and
not closely related to the remaining eastern species of Aphyosemion (W. J. Murphy
and G. E. Collier, 1997, Mol. Biol. Evol. 14, 790-799). This is supported by
further analysis of mitochondrial DNA sequences from 19 species from 21 different
localities, representing 19 of the putative 22 species of this western group.
Phylogenetic analyses of these data corroborate the monophyly and sister-group
relationship of two distinct groups of taxa: Callopanchax and Scriptaphyosemion.
Many of the relationships within Scriptaphyosemion suggest that these taxa may
have radiated within a short period of time relative to the rate of substitutions
within these sequences. A third, and possibly paraphyletic group of species,
Archiaphyosemion, is suggested to be the sister taxon to the first two groups.
These three groups are elevated to generic rank and together represent the sister
group to the genus Epiplatys. Biogeographic inference suggests that the ancestors
of this group diversified westward through upland habitat and have only
relatively recently entered the lowland habitats in which Scriptaphyosemion and
Callopanchax have diversified, with the latter genus reacquiring a suite of
traits collectively referred to as annualism.
PMID- 10196077
TI - Phylogenetic relationships of African killifishes in the genera Aphyosemion and
Fundulopanchax inferred from mitochondrial DNA sequences.
AB - We have analyzed the phylogenetic relationships of 52 species representing all
defined species groups (J. J. Scheel, 1990, Atlas of Killifishes of the Old
World, 448 pp.) of the African aplocheiloid fish genera Aphyosemion and
Fundulopanchax in order to examine their interrelationships and to reveal trends
of karyotypic evolution. The data set comprised 785 total nucleotides from the
mitochondrial 12S rRNA and cytochrome b genes. The molecular-based topologies
analyzed by both maximum parsimony and neighbor-joining support the monophyly of
most previously defined species groups within these two killifish genera. The
genus Aphyosemion is monophyletic except for the nested position of
Fundulopanchax kunzi (batesi group; subgenus Raddaella) within this clade,
suggesting that this taxon was improperly assigned to Fundulopanchax. The
remaining Fundulopanchax species sampled were supported as being monophyletic in
most analyses. Relationships among the species groups in both genera were not as
strongly supported, suggesting that further data will be required to resolve
these relationships. Additional sampling from the 16S rRNA gene allowed further
resolution of relationships within Fundulopanchax, more specifically identifying
the nonannual scheeli group as the basal lineage of this otherwise annual genus.
Chromosomal evolution within Aphyosemion has been episodic, with the evolution of
a reduced n = 9-10 metacentric complement having occurred in multiple,
independent lineages. Polarity of chromosomal reductions within the elegans
species group appears to support previous hypotheses concerning mechanisms of
karyotypic change within the genus Aphyosemion.
PMID- 10196079
TI - Phylogeny of salmonine fishes based on growth hormone introns: Atlantic (Salmo)
and Pacific (Oncorhynchus) salmon are not sister taxa.
AB - Though salmonid fishes are a well-studied group, phylogenetic questions remain,
especially with respect to genus-level relationships. These questions were
addressed with duplicate growth hormone (GH) introns. Intron sequences from each
duplicate gene yielded phylogenetic trees that were not significantly different
from each other in topology. Statistical tests supported validity of the
controversial monotypic genus Parahucho, monophyly of Oncorhynchus, and inclusion
of Acantholingua ohridana within Salmo. Suprisingly, GH1 intron C (GH1C) did not
support the widely accepted hypothesis that Oncorhynchus (Pacific salmon and
trout) and Salmo (Atlantic salmon and trout) are sibling genera; GH2C was
ambiguous at this node. Previously published data were also examined for support
of Salmo and Oncorhynchus as sister taxa and only morphology showed significant
support. If not sister taxa, the independent evolution of anadromy-the migration
to sea and return to freshwater for spawning-is most parsimonious. While there
was incongruence with and among published data sets, the GH1C intron phylogeny
was the best hypothesis, based on currently available molecular data.
PMID- 10196078
TI - Internal transcribed spacer sequence phylogeny of Crambe L. (Brassicaceae):
molecular data reveal two Old World disjunctions.
AB - Crambe L. (Brassicaceae) is an Old World genus with a disjunct distribution among
four major centers of species diversity. A phylogenetic analysis of nucleotide
sequences of the internal transcribed spacers (ITS) of the nuclear ribosomal
repeat was conducted with 27 species of Crambe and 18 related genera. Cladistic
analyses using weighted and unweighted parsimony support Crambe as a monophyletic
genus with three major lineages. The first comprises those taxa endemic to the
Macaronesian archipelagos. Taxa with a predominant Mediterranean distribution
form the second assemblage, and a disjunction between east Africa (C. abyssinica)
and the Mediterranean (C. hispanica) occurs in this clade. The third lineage
includes all Eurosiberian-Asian taxa and C. kilimandscharica, a species from the
highlands of east Africa. A basal biogeographic split between east Africa and
Eurasia is present in the third clade. The patterns of relationships in the ITS
tree are concordant with known climatic events in northern Africa and
southwestern Asia since the middle Miocene. The ITS trees are congruent with the
current sectional classification except for a few members of sections Crambe,
Leptocrambe, and Orientecrambe (C. cordifolia, C. endentula, C. kilimandscharica,
and C. kotschyana). Low levels of support in the basal branches do not allow
resolution of which genera of the subtribes Raphaniae or Brassicinae are sister
to Crambe. Both subtribes appear to be highly polyphyletic in the ITS trees.
PMID- 10196080
TI - Origin of the unisexual lizard Gymnophthalmus underwoodi (Gymnophthalmidae)
inferred from mitochondrial DNA nucleotide sequences.
AB - Analysis of variation in nucleotide sequences in mitochondrial DNA genes among
species of Gymnophthalmus supports three major conclusions. First, samples of G.
underwoodi, a unisexual species of hybrid origin, have identical nucleotide
sequences, supporting the hypothesis that all individuals from localities in the
Guianan Region of South America and the Lesser Antilles descended from a single
hybridization event. Second, G. underwoodi and G. cryptus share derived
similarities in nucleotide sequences of the maternally inherited mitochondrial
DNA, suggesting that the female participant in the hybridization event that
produced the hybrid species was either G. cryptus or most closely related to it.
Last, phylogenetic analyses recovered historical structure among population
samples of G. speciosus supporting previous claims that there is unrecognized
diversity under that binomial, and some analyses suggest that G. speciosus does
not comprise a natural group.
PMID- 10196081
TI - Molecular phylogeny of the Ceratosolen species pollinating Ficus of the subgenus
Sycomorus sensu stricto: biogeographical history and origins of the species
specificity breakdown cases.
AB - The 14 species of Ficus of the subgenus Sycomorus (Moraceae) are invariably
pollinated by Ceratosolen species (Hym. Chalcidoidea), which in turn reproduce in
the fig florets. They are distributed mostly in continental Africa, Madagascar,
and the Mascarene and Comoro Islands, but 1 species extends its geographical
range all over the Oriental region. Fig-pollinator relationships are usually
strictly species specific, but exceptions to the 'one-to-one' rule occur within
the group we studied. In order to understand both the biogeographical history of
the Ceratosolen species associated with Ficus of the subgenus Sycomorus and the
origins of the specificity breakdown cases, we have used cytochrome b sequences
to reconstruct a phylogeny of the fig wasps. The results show that the
pollinators from the Malagasy region and those from continental Africa form two
distinct clades, which probably diverged after the crossing of the Mozambique
Channel by an ancestral population. The Oriental wasp species show strong
affinities with the African species. The two species-specificity exceptions are
due to different evolutionary events. The occurrence of the two West African
pollinators associated with F. sur can be explained by successive speciation
events of the mutualistic partner without plant radiation. In contrast, we
hypothesize that C. galili shifted by horizontal transfer from an unknown,
presumably extinct, Ficus species to F. sycomorus after this native Malagasy fig
species colonized Africa.
PMID- 10196083
TI - Evolution of a mitochondrial cytochrome b gene sequence in the species-rich genus
sebastes (Teleostei, Scorpaenidae) and its utility in testing the monophyly of
the subgenus Sebastomus.
AB - The ecologically diverse and species-rich rockfishes (Sebastes) are a useful
group for the study of marine speciation. The monophyly of the genus is generally
accepted, as is the validity of most of the numerous species found along the West
Coast of North America. However, the subgeneric groupings that would help in the
proposal and interpretation of various speciation schemes are poorly supported
based on widely overlapping morphological characters. The use of genetic
characters provides an alternative approach. In this study, we present the first
quantitative analysis supporting the monophyly of all 14 species of the subgenus
Sebastomus among 54 congeners. The structural features and evolution of the 750
bp of the cytochrome b gene used to test the monophyly were similar to those of
other vertebrates. Low levels of intrageneric sequence divergence (<10%) and
incipient levels of saturation at third-codon positions were found in the gene.
The monophyly of Sebastomus was supported in extensive phylogenetic analyses
using distance, cladistic, and likelihood methods. Further corroboration was
obtained from permutation- and simulation-based statistical tests.
PMID- 10196082
TI - The phylogenetic relationships of the suborder Acanthuroidei (Teleostei:
Perciformes) based on molecular and morphological evidence.
AB - Fragments of 12S and 16S mitochondrial DNA genes were sequenced for 14
acanthuroid taxa (representing all six families) and seven outgroup taxa. The
combined data set contained 1399 bp after removal of all ambiguously aligned
positions. Examination of site saturation indicated that loop regions of both
genes are saturated for transitions, which led to a weighted parsimony analysis
of the data set. The resulting tree topology generally agreed with previous
morphological hypotheses, most notably placing the Luvaridae within the
Acanthuroidei, but it also differed in several areas. The putative sister group
of Acanthuroidei, Drepane, was recovered within the suborder, and the sister
group of the family Acanthuridae, Zanclus, was likewise recovered within the
family. Morphological characters were included to produce a combined data set of
1585 characters for 14 acanthuroid taxa and a single outgroup taxon. An analysis
of the same 15 taxa was performed with only the DNA data for comparison. The
total-evidence analysis supports the monophyly of the Acanthuridae. A parametric
bootstrap suggests the possibility that the paraphyly of Acanthuridae indicated
by the molecular analyses is the result of long-branch attraction. The
disagreement between molecular and morphological data on the relationships of the
basal acanthuroids and its putative sister taxon is unresolved.
PMID- 10196084
TI - Molecular evolution, systematics, and zoogeography of the rockfish subgenus
Sebastomus (Sebastes, Scorpaenidae) based on mitochondrial cytochrome b and
control region sequences.
AB - Sebastomus is one of the most species-rich subgenera of Sebastes, whose monophyly
is well supported by morphological and molecular data. We present the first
description of the complete nucleotide sequence of the mitochondrial cytochrome b
gene and the partial sequence of the control region of the 14 species of
Sebastomus. We used these data in phylogenetic analyses to investigate their
evolutionary relationships. Extremely low levels of sequence divergence indicated
a recent ancestry of these species, suggesting a very rapid radiation within the
last million years. The molecular data revealed two main clades within
Sebastomus, each with species of different affinities that invaded new habitats
from the subgeneric center of distribution. The rapid speciation in this lineage
was manifested in the poor resolution of some nodes in the phylogeny. Internal
fertilization and viviparity in Sebastes may have played an important role in the
sudden acquisition of reproductive barriers during its radiation. The
mitochondrial DNA data suggest that prolific speciation in Sebastomus may have
been associated with rapid lineage sorting punctuated by allopatric reproductive
isolation subsequent to dispersal events and, perhaps, by sympatric reproductive
isolation associated with internal fertilization.
PMID- 10196085
TI - Phylogenetic relationships of the New World monkeys (Primates, platyrrhini) based
on nuclear G6PD DNA sequences.
AB - In order to test hypotheses about the phylogenetic relationships among living
genera of New World monkeys, 1.3 kb of DNA sequence information was collected for
two introns of the glucose-6-phosphate dehydrogenase (G6PD) locus, encoded on the
X chromosome, for 24 species of New World monkeys. These data were analyzed using
a maximum parsimony algorithm. The strict consensus of the three most
parsimonious gene trees that result shows support for the following clades: a
pitheciine clade including Callicebus within which Chiropotes and Cacajao are
sister taxa, an Alouatta-atelin clade within which Brachyteles is the sister
taxon of Lagothrix and which is sister to another clade containing the
callitrichines, and a callitrichine/Aotus/Cebus/Saimiri clade. Within the
callitrichines, Callimico is the sister taxon of Callithrix. Cebus and Saimiri
form a clade. These results are broadly consistent with previously published DNA
sequence analyses of platyrrhine phylogeny and provide additional support for
groupings provisionally proposed in those earlier studies. Nevertheless,
questions remain as to the relative phylogenetic placement of Leontopithecus and
Saguinus, the branching order within the Aotus/Cebus/Saimiri/callitrichine clade,
and the placement of the pitheciine clade relative to the atelines and the
callitrichines.
PMID- 10196086
TI - Single-locus tests of microsatellite evolution: multi-step mutations and
constraints on allele size.
AB - We evaluate some common simulation procedures as well as a recently developed
likelihood method used for testing hypotheses regarding microsatellite evolution.
Results from simulated data revealed that the tests for the detection of multi
step mutations in general have some power, whereas tests for the presence of
constraints on the repeat number have only very limited power. The tests were
applied to population data obtained from nine different baleen whale populations.
High agreement was found between results obtained using the simulation-based
approach and results obtained using a likelihood ratio test. In four of the nine
population samples the tests rejected the one-step mutation model. In two
instances the significant deviation was due to excess of heterozygosity and in
two instances to a reduced level of heterozygosity relative to the expectations
under the stepwise mutation model. The former significant deviation was
consistent with occasional multi-step mutations, whereas the latter may indicate
the presence of constraints on the number of repeats.
PMID- 10196087
TI - Stochastic mechanism of cellular aging--abrupt telomere shortening as a model for
stochastic nature of cellular aging.
AB - A strong stochastic component has been described for the appearance of senescent
cells in cultures that have not completed their in vitro lifespan. The
proliferative potential of individual clones show a bimodal distribution.
Additionally, two cells arising from a single mitotic event can exhibit large
differences in their doubling capacities. In this report we present a model and a
computer simulation of the model that explains the observed stochastic phenomena.
The model is based on both gradual and abrupt telomere shortening. Gradual
telomere shortening (GTS) occurs during each cell division as a consequence of
the inability of DNA polymerase to replicate the very ends of chromosomal DNA. It
is responsible for the gradual decline in proliferative potential of a cell
culture, but does not explain the stochastic aspects of cellular aging. Abrupt
telomere shortening (ATS) occurs either through DNA recombination or nuclease
digestion at the subtelomeric/telomeric border region of the chromosome.
Recombination involves the invasion of a telomere single-strand three-prime
protruding end at this border in the telomere of the same chromosome or in
another subtelomeric/telomeric region. Shortening of one or more telomeres in the
cell causes a sudden onset of cell senescence, referred to as sudden senescence
syndrome (SSS). This is manifested as a stochastic and abrupt transition of cells
from the larger to the smaller proliferative potential pool and can cause cell
cycle arrest within one cell division. The computer simulation matches well with
experimental data supporting the prediction that abrupt telomere shortening
underlies the stochastic onset of cell senescence. Sudden senescence syndrome
appears to be the most important mechanism in the control of the extent of
proliferation of a cell culture because it prevents virtually every cell in the
culture from reaching its maximum doubling capacity, that would otherwise be
allowed by telomere shortening via the end-replication mechanism alone.
PMID- 10196088
TI - Predictors of light-limited growth and competition of phytoplankton in a well
mixed water column
AB - Based on a model of light limited growth, Huisman and Weissing found that in a
well mixed water column with constant light supply (energy reaching the water
surface), equilibrium growth and competition of phytoplankton for light can be
characterised by a critical light intensity at the base of the column (I*out).
The present study attempts to give a further insight into this model. We first
analyse the dependence of the critical light intensity on four parameters:
initial slope of the photosynthesis-intensity (p-I) curve, maximal photosynthetic
rate, the light-saturated parameter Ikand specific carbon loss rate. Increases in
the first two parameters tend to reduce the critical light intensity and
increases in the last two tend to increase the critical light intensity. Then we
analyse the performance of a model under variable light supply with a time-scale
of 1 day (24 hr). Within this time-scale, the critical light intensity changes
with time. However, the equilibrium growth and the outcome of competition for
light can be adequately characterised by critical light extinction defined as the
upper limit of total light extinction due to both biomass and non-living matter
in the water column. Under constant light supply, a critical light intensity
uniquely corresponds to a critical light extinction. Therefore, critical light
extinction can be utilised to predict the equilibrium growth and the outcome of
competition under both constant and variable light supply. By changing the
maximal light supply at noon, seasonal succession of species composition of
communities is investigated. The possible effect of two typical photoresponses,
photoadaptation and photoinhibition, on growth and competiton are discussed.
Copyright 1999 Academic Press.
PMID- 10196089
TI - A p-Adic model for the process of thinking disturbed by physiological and
information noise.
AB - We develop a model of the process of thinking in the presence of noise (which is
produced by the simultaneous action of a huge number of neurons in the brain as
well as by external information and internal cognitive processes). Our model is
based on Freud's idea on the splitting of cognitive processes into two (closely
connected) domains: consciousness and subconsciousness. We represent the process
of thinking as a random dynamical process in a space of ideas endowed with a non
Euclidean geometry (which differs extremely from the ordinary Euclidean geometry
of spatial location of neurons in the brain). The so-called p-adic geometry on a
space of ideas describes the ability of cognitive systems to form associations.
We show that random dynamical thinking systems on a p -adic space of ideas still
generate only deterministic ideas. We also study positive and negative effects of
noise (in particular, creativeness and stress).
PMID- 10196090
TI - What pair formation can do to the battle of the sexes: towards more realistic
game dynamics.
AB - In the various dynamic models of Dawkin's Battle of the Sexes, payoff matrices
serve as the basic ingredients for the specification of a game-dynamic model.
Here I model the sex war mechanistically, by expressing the costs of raising the
offspring and performing a prolonged courtship via a time delay for the
corresponding individuals, instead of via payoff matrices. During such a time
delay an individual is not able to have new matings. Only after the delay has
occurred, an individual (and its offspring) appears on the mating market again.
From these assumptions I derive a pair-formation submodel, and a system of delay
differential equations describing the dynamics of the game. By a time-scale
argument, I obtain an approximation of this system by means of a much simpler
system of ordinary differential equations. Analysis of this simplified system
shows that the model can give rise to two non-trivial asymptotically stable
equilibrium points: an interior equilibrium where both female strategies and both
male strategies are present, and a boundary equilibrium where only one of the
female strategies and both male strategies are present. This behaviour is
qualitatively different from that of models of the battle of the sexes formulated
in the traditional framework of game-dynamic equations. In other words, the
addition of a most elementary further assumption about individual life history
fundamentally changes the model predictions. These results show that in analysing
evolutionary games one should pay careful attention to the specific mechanisms
involved in the conflict. In general, I advocate deriving simple models for
evolutionary games, starting from more complex, mechanistic building blocks. The
wide-spread method of modelling games at a high phenomenological level, through
payoff matrices, can be misleading.
PMID- 10196091
TI - Sex specific X chromosome expression caused by genomic imprinting.
AB - The conflict theory of genomic imprinting predicts that imprinted genes are
growth enhancing when paternally expressed and growth suppressing when maternally
expressed. The expression pattern of autosomal imprinted genes generally fits
these predictions. However, the conflict theory cannot easily account for the
pattern of X-linked imprinting in humans and mice. This has led us to propose a
novel hypothesis that X-linked imprinting has evolved to control sex specific
gene expression in early embryos. The hypothesis links paternal X-imprinting
(i.e. paternal copy silencing) to random X-inactivation and the retention of Y
linked copies, and links maternal X-imprinting to escape from random X
inactivation and the loss of Y-linked copies. The hypothesis offers a good
explanation of the existing data on X-imprinted genes.
PMID- 10196092
TI - Reaction-diffusion-advection model for pattern formation of rhythmic contraction
in a giant amoeboid cell of the physarum plasmodium
AB - The plasmodium of Physarum polycephalum is a large amoeboid organism showing
rhythmic contraction everywhere within an organism, and moves by forming spatio
temporal patterns of the rhythmic contraction. We propose a reaction-diffusion
advection model for the pattern formation. This model is constructed under
physiological suggestions that the chemical oscillator acts as a clock regulating
the rhythmic contraction and interacts spatially not only by diffusion but also
by advection of protoplasm. Behavior of the model is studied by numerical
calculation, especially the effects of the advection term on a simple reaction
diffusion system. The advection effect reproduces experimentally observed
phenomena of fluctuating propagation of the contraction wave. Concept of the
reaction-diffusion-advection system is promising for modeling the mechanism of
amoeboid behaviour in the Physarum plasmodium. Copyright 1999 Academic Press.
PMID- 10196093
TI - The disappearing CD4(+)T cells in HIV infection: a case of over-stimulation?
AB - Infection with the human immunodeficiency virus (HIV) causes a gradual decline in
essential immune-system cells called CD4(+)"helper" T cells. These cells are also
principal viral targets, but, paradoxically, direct cell-killing does not explain
their disappearance. HIV also induces a chronic and increasing state of immune
activation. In a mathematical model of normal T-cell kinetics incorporating a
cytokine growth factor, increased activation alone explains these T-cell losses,
a switch from "naive" to "memory" phenotype, and certain other features of HIV
disease.
PMID- 10196094
TI - On fractal properties of arterial trees.
AB - The question of fractal properties of arterial trees is considered in light of
data from the extensive tree structure of the right coronary artery of a human
heart. Because of the highly non-uniform structure of this tree, the study
focuses on the purely geometrical rather than statistical aspects of fractal
properties. The large number of arterial bifurcations comprising the tree were
found to have a mixed degree of asymmetry at all levels of the tree, including
the depth of the tree where it has been generally supposed that they would be
symmetrical. Cross-sectional area ratios of daughter to parent vessels were also
found to be highly mixed at all levels, having values both above and below 1.0,
rather than consistently above as has been generally supposed in the past.
Calculated values of the power law index which describes the theoretical relation
between the diameters of the three vessel segments at an arterial bifurcation
were found to range far beyond the two values associated with the cube and square
laws, and not clearly favoring one or the other. On the whole the tree structure
was found to have what we have termed "pseudo-fractal" properties, in the sense
that vessels of different calibers displayed the same branching pattern but with
a range of values of the branching parameters. The results suggest that a higher
degree of fractal character, one in which the branching parameters are constant
throughout the tree structure, is unlikely to be attained in non-uniform vascular
structures.
PMID- 10196095
TI - How costly is the honest signaling of need?
AB - ESS models of biological signaling have shown that costly signals can provide
honest information. In the context of parent-offspring conflict over the
allocation of resources by parents to their young, the theory explains costly
offspring solicitation behavior as an accurate signal of offspring need to
parents who cannot assess offspring condition directly. In this paper, we provide
a simple but general characterization of the honest signaling of need in models
of parent-offspring conflict: the offspring's signaling cost is proportional to
the parent's fitness loss from satisfying the offspring's resource requirement.
The factor of proportionality is given by a measure of the extent of parent
offspring conflict that depends only on coefficients of relatedness. These
results hold for interbrood conflict with uniparental investment even if the
relationship between offspring condition and resource requirement is not
monotonic, and extend to cases of biparental care, uncertainty concerning the
parent's condition, and intra-brood conflict. Copyright 1999 Academic Press.
PMID- 10196096
TI - Risky business: sexual and asexual reproduction in variable environments.
AB - Patterns of reproductive uncertainty can have an important influence on
population dynamics. There is a crucial distinction between what we describe here
as aggregate uncertainty (in which reproductive output in each generation is
correlated among the individuals in a population) and idiosyncratic risk (in
which reproductive output is independent across individuals). All else being
equal, populations experiencing idiosyncratic risk enjoy a higher asymptotic
growth rate than do those experiencing aggregate uncertainty. Therefore
individuals in populations of the former type will have a competitive advantage
over individuals in populations of the latter type. Applying this distinction to
models of randomly fluctuating environments, we point out that genetic variation
among offspring can serve to reduce aggregate uncertainty, transforming it into a
more idiosyncratic form of risk. We show that this transformation underlies the
dynamics observed in several previous models of the role of outcrossing in the
evolution of sex.
PMID- 10196097
TI - A kinetic model of the system: tyrosyl radical-nitrogen oxide-superoxide ion.
AB - It is generally recognized that the initial step in the formation of
atherosclerotic plaque in humans involves the peroxidation of low density
lipoproteins (LDL). However, there is no agreement on the mechanism that
initiates peroxidation. Among the candidates are several that involve tyrosyl
radical, nitrogen oxide, and superoxide ion or their mutual reaction products. In
this paper a kinetic model of this system is constructed that examines the nature
of these reactions, and places some constraints on their possible overall
contribution to the initiation of peroxidation. The reversible reaction of nitric
oxide and tyrosyl radical acts to "buffer" tyrosyl radical concentrations while
the reaction of tyrosyl radical with superoxide ion scavenges tyrosyl radical.
Quantitatively, the reaction of nitric oxide with superoxide to form
peroxynitrite is a more important process, but the physiological significance
would appear to be related to details of the decay of peroxynitrite that are
still in dispute.
PMID- 10196098
TI - Database search strategies used to isolate cell death proteins.
AB - The identification of proteins involved in the early phases of cell death has
relied primarily on the modular organization of shared sequences and structural
motifs of previously identified proteins in the apoptotic machinery. This
property has facilitated the isolation of proteins that interact with each other
through structural domains using yeast two-hybrid cloning. Likewise, the
conservation in primary sequence of the various shared domains has promoted the
use of polymerase chain reaction and database search strategies to isolate
additional family members. Here, we discuss the use of database search strategies
in the isolation of novel death proteins, as well as how similar strategies may
be extended to discover additional, novel cell death proteins.
PMID- 10196099
TI - Isolation and analysis of components of CD95 (APO-1/Fas) death-inducing signaling
complex.
AB - CD95 (APO-1/Fas) is an apoptosis-inducing receptor belonging to the tumor
necrosis factor receptor superfamily. Multimerization of CD95 leads to instant
recruitment of the signaling molecules FADD and caspase-8 to the activated
receptor forming the death-inducing signaling complex (DISC). DISC formation is
the first essential step of CD95 signaling and results in activation of caspase-8
starting a signaling cascade that leads to apoptosis. Here we describe a method
for analyzing the CD95 DISC. The method is based on coimmunoprecipitation of the
signaling molecules with the activated CD95 receptor followed by Western blot
detection of associated molecules. Therefore, this method can analyze the very
first signaling events during CD95-mediated apoptosis.
PMID- 10196100
TI - Methods of assaying Bcl-2 and Bax family proteins in yeast.
AB - Bcl-2 family proteins play an evolutionarily conserved role in regulating the
life and death of the cell. Certain proapoptotic members of the Bcl-2 family, Bax
and Bak, have intrinsic cytotoxic activities in that they not only induce or
sensitize mammalian cells to undergo apoptosis but also display a lethal
phenotype when ectopically expressed in two yeast species Saccharomyces
cerevisiae and Schizosaccharomyces pombe. Furthermore, the antiapoptotic Bcl-2
and Bcl-XL proteins can protect yeast against Bax-mediated lethality, suggesting
that the death-regulatory functions of these Bcl-2 family proteins are well
preserved in yeast. These observations provide the opportunity to study the
function of Bcl-2 family proteins in genetically tractable yeast and to apply
classical yeast genetics and functional cloning approaches to the dissection of
programmed cell death pathway regulated by Bcl-2 family proteins. We describe
here methods used in our laboratory to express and to study the functions of Bcl
2 family proteins in both the budding yeast S. cerevisiae and the fission yeast
S. pombe.
PMID- 10196101
TI - Use of gene knockouts in cultured cells to study apoptosis.
AB - The avian DT40 cell system represents a novel method to generate loss of function
mutations in vertebrate cells. These chicken B lymphoma cells undergo homologous
recombination at very high frequencies and can thus be used to "knock out" genes
believed to function in apoptotic processes. The knockout cells can then be used
to determine how the cell death process is modulated after induction of apoptosis
and to order components in cell death pathways. The system can be further
modified, using tetracycline-responsive promoters, to allow expression of wild
type cDNAs to rescue "knockout cells" if the gene of interest is essential.
Alternatively, cDNA expression constructs containing mutations or deletions in
the cDNA encoding the absent protein can be used to delineate functional domains.
cDNA expression libraries or known proteins believed to function downstream of
the target in a signal transduction pathway could also be transfected into the
knockout cell line, and the resultant cells could be assayed for complementation
and/or rescue of the apoptotic alteration/defect. Finally, the system has
recently been adapted to allow disruption of human genes in DT40/human hybrid
cell lines thereby potentially extending this system for use in studying human
genes.
PMID- 10196102
TI - Caspases: preparation and characterization.
AB - Caspases and their involvement in programmed cell death have been an area of
significant interest since their initial identification in 1992. To facilitate
the search for new components involved in cell death, and to aid researchers in
understanding the interactions between currently known cell death proteins, we
describe a number of techniques commonly used in the preparation and
characterization of caspases.
PMID- 10196103
TI - Irreversible caspase inhibitors: tools for studying apoptosis.
AB - Irreversible inhibitors of caspase proteases are often used in studies of
apoptosis. However, vigorous interpretation of data generated with irreversible
inhibitors requires quantitative analysis of their effects on enzyme kinetics. A
simple method for the quantitative analysis of affinity irreversible inhibitors
is introduced. The method allows simultaneous measurement of the dissociation
constant Ki for the reversible binding to a caspase and the first-order rate
constant k3 for the subsequent in situ covalent reaction that follows the
noncovalent binding. The Ki value provides information regarding the affinity of
an inhibitor for the enzyme, whereas the k3 value provides a measure of the in
situ reactivity between the reactive functional groups of the bound inhibitor and
the nearby nucleophilic side chain at the protease active site. This two-step
kinetic analysis offers a more complete description of the characteristics of an
irreversible inhibitor than does the commonly used second-order rate constant.
The method has been applied to a library of irreversible caspase inhibitors. We
demonstrate how the resulting quantitative inhibitory constants can be used to
identify key caspase activities responsible for apoptosis in specific cellular
models.
PMID- 10196104
TI - Detection of DNA fragmentation and endonucleases in apoptosis.
AB - DNA degradation during apoptosis is endonuclease mediated and proceeds through an
ordered series of stages commencing with the production of large DNA pieces of
300 kb which are then degraded to fragments of 50 kb. The 50-kb fragments are
further degraded, in some but not all cells, to smaller pieces (10-40 kb)
releasing the small oligonucleosome fragments that are detected as a
characteristic DNA ladder on conventional agarose gels. Methodology is presented
for the detection of both DNA ladders and the initial stages of DNA fragmentation
using pulsed-field gel electrophoresis. We have developed electrophoresis
conditions that resolve large fragments of DNA and also retain the smaller
fragments on the same gel. Methods for the detection of endonuclease activities
responsible for the cleavage of DNA during apoptosis are also presented.
PMID- 10196105
TI - 5HT antagonists attenuate MK801-impaired radial arm maze performance in rats.
AB - Glutamatergic hypofunction occurs in Alzheimer's disease (AD). MK801, a
noncompetitive blocker of glutamate N-methyl-D-aspartate receptors, was used to
disrupt the cognitive performance of rats trained on a delayed nonmatching to
sample radial maze task. Drugs which act by blocking serotonin (5-HT) receptors
were evaluated for their ability to reduce the cognitive impairment produced by
MK801. Specifically, WAY-100635, a selective 5-HT1A receptor antagonist,
buspirone, a 5-HT1A partial agonist, ritanserin, a 5-HT2 antagonist, and
ondansetron, a 5-HT3 antagonist, were assessed. In addition, the muscarinic
agonist arecoline was evaluated for its potential cognitive benefit in this
model. It was found that WAY-100635 significantly reduced the cognitive
impairment induced by MK801. Treatment with single doses of ritanserin,
ondansetron, or arecoline in combination with MK801 did not result in a cognitive
impairment, indicating that these drugs attenuated the MK801 impairment. The
combination of buspirone and MK801 resulted in an inability of the animals to
complete the task. These results suggest that interactions between 5-HT and
glutamate may mediate the beneficial effects of reducing cognitive impairment and
that 5-HT antagonists, especially selective 5-HT1A antagonists, may be useful in
treating AD. Further, it is indicated that the MK801 model of cognitive
impairment may add to the armamentarium of tools available to predict treatment
efficacy in AD.
PMID- 10196106
TI - Interactions between perinatal and neonatal associative learning defined by
contiguous olfactory and tactile stimulation.
AB - Tactile stimulation of the neonate, as performed by the mother during and after
delivery, has been described as an effective unconditioned stimulus during early
ontogeny (Leon, 1987; Ronca & Alberts, 1994). The present experiments examined
the interaction between perinatal and neonatal learning determined by the
explicit association between alcohol odor and vigorous body stimulation of the
perinatal organism. In Experiment 1, rat fetuses were exposed to either alcohol
or saline 10 min prior to cesarean delivery. The alcohol administration procedure
here employed was sufficient to provide sensory contamination of the amniotic
fluid but avoid fetal alcohol intoxication. Pups in the two prenatal treatments
later experienced the smell of alcohol, tactile stimulation, or both stimuli
explicitly paired or unpaired. Other postnatal groups were composed of pups that
had no explicit experience with either experimental stimulus. Pups subjected to
alcohol odor in utero displayed more overall motor activity in response to that
odor than saline controls. The increased motor responses were further potentiated
in pups that experienced additional postnatal alcohol odor paired with tactile
stimulation. In Experiment 2, pups were exposed to alcohol in the amniotic fluid
10 or 30 min prior to birth. As previously demonstrated the memory acquired in
utero appears highly dependent upon contingency between exposure to this
particular scent and delivery procedures. Pups in both prenatal treatment groups
were then exposed to alcohol odor paired or unpaired with tactile stimulation.
Some control animals received no further experience with either stimuli. Those
pups exposed to alcohol odor paired with tactile stimulation both pre- and
postnatally later showed maximum motor activity elicited by the odor of alcohol.
The results support the notion of fetal associative learning comprising alcohol's
chemosensory cues and behaviorally activating stimuli. Furthermore, the
conditioned response under analysis is potentiated whenever neonates are
reexposed to contingent presentations of the elements that defined the original
associative memory.
PMID- 10196107
TI - Enhanced release of norepinephrine in rat hippocampus during spontaneous
alternation tests.
AB - Recent evidence suggests that release of acetylcholine (ACh) in the hippocampus
is associated with performance on a spontaneous alternation task and with
enhancement of that performance by systemic and central injections of glucose.
The present study extended these findings by examining norepinephrine (NE)
release in the hippocampus using in vivo microdialysis while rats were tested for
spontaneous alternation performance with and without prior injections (ip) of
glucose. Microdialysis samples were collected every 12 min and assayed for NE
content by HPLC-ECD. Like ACh, NE release in hippocampus increased during
spontaneous alternation testing. As in past experiments, administration of
glucose (250 mg/kg) significantly enhanced alternation scores. However, glucose
did not influence NE release either during behavioral testing or at rest. These
findings contrast with prior evidence showing that glucose augments testing
related increases in ACh release. The findings suggest that norepinephrine is
released within the hippocampus while rats are engaged in alternation
performance. However, increased release of norepinephrine apparently does not
contribute to the enhancement of alternation scores produced by glucose.
PMID- 10196108
TI - Effects of the novel acetylcholinesterase inhibitor N-octyl-1,2,3, 4-tetrahydro-9
aminoacridine on locomotor activity and avoidance learning in mice.
AB - The acetylcholinesterase reversible inhibitor N-octyl-1,2,3, 4-tetrahydro-9
aminoacridine (THA-C8) is a new synthesized derivative of tacrine (THA)
characterized by an alkyl chain in the molecular structure which ameliorates the
penetrability of the compound into the central nervous system. THA-C8 (0.1-5
mg/kg) significantly reduced spontaneous locomotor activity in CD1 mice at a dose
of 3 mg/kg. Moreover, THA-C8 (0.2-2 mg/kg) significantly improved shuttle-box
avoidance acquisition at doses (0.25, 0.3, 1 mg/kg) not affecting locomotion and
that are much lower than the doses reported to be effective for THA in animal
models. From the data reported it seems that the new compound could be
interesting for therapeutic purposes.
PMID- 10196109
TI - Enhanced learning by posttrial injection of H1-but not H2-histaminergic
antagonists into the nucleus basalis magnocellularis region.
AB - The aim of this study was to examine the effects of histaminergic antagonists on
memory upon injection into the region of the nucleus basalis magnocellularis
(NBM). In experiment 1, rats with chronically implanted cannulae were trained on
the uphill avoidance task, which involves a punishment of a high-probability
turning response on a tilted platform (negative geotaxis). Immediately after the
training trial, that is, after a tail shock was administered upon performing the
response, rats received one microinjection (0.5 microliter) of H1-receptor
blocker chlorpheniramine (dose range 0.1 to 20 microgram) or the H2-receptor
blocker ranitidine (same dose range) or saline into the NBM region. When tested
24 h later, rats treated with chlorpheniramine (20 micrograms) had significantly
longer uphill latencies than vehicle controls and ranitidine-treated animals,
indicative of superior learning of the avoidance response. In experiment 2, a
test for possible proactive effects of posttrial chlorpheniramine on performance
during the retention trial was performed. Animals were injected with either 20
micrograms chlorpheniramine or saline immediately after the training trial of the
uphill task. One chlorpheniramine control group was treated with a delay of 5 h.
Additional groups which received chlorpheniramine or vehicle after the training
trial but no trail shock were included. When tested 24 h later, rats injected
with 20 micrograms chlorpheniramine again exhibited significantly longer uphill
latencies than did vehicle-injected rats. Retention latencies for the rats of the
chlorpheniramine 5-h delayed group did not differ from those of the vehicle
injected rats, ruling out proactive effects of chlorpheniramine on performance.
In summary, the histaminergic H1-blocker chlorpheniramine can enhance mnemonic
functioning in addition to its reinforcing effects upon NBM injection as reported
previously.
PMID- 10196111
TI - Side-chains configurations in coiled coils revealed by the 5.15-A meridional
reflection on hard alpha-keratin X-ray diffraction patterns.
AB - The origin of the 5.15-A meridional reflection on hard alpha-keratin X-ray
diffraction patterns is discussed in terms of side-chains conformations. We show
it to reveal specific configurations of the side chains which are common to all
two-stranded alpha-helical coiled coils. Combining literature data on
crystallised coiled coil pieces and molecular dynamics results with our X-ray
diffraction pattern simulations, we propose rules for the attribution of chi1
torsion angles for coiled coils involved in fibres whose structure cannot be
resolved at atomic resolution: in a (a b c d e f g) heptad repeat, a and d
residues, respectively, adopt mean t and g+ configurations, whereas statistical
rules are given for the other residues.
PMID- 10196110
TI - Deficit in selective and divided attention associated with cholinergic basal
forebrain immunotoxic lesion produced by 192-saporin; motoric/sensory deficit
associated with Purkinje cell immunotoxic lesion produced by OX7-saporin.
AB - The immunotoxin 192-saporin, infused intracerebroventricularly into rats,
destroys cholinergic neurons in the basal forebrain nuclei. Doses required for
complete cholinergic loss also kill some Purkinje cells. The immunotoxin OX7
saporin, when infused intraventricularly into rats, destroys Purkinje cells in a
pattern similar to that produced by 192-saporin, without affecting cholinergic
neurons. Thus, we used OX7-saporin to distinguish behavioral effects of 192
saporin due to cerebellar damage versus those due to cholinergic cell loss. Three
doses of 192-saporin (1.6, 2.6, and 3.3 micrograms/rat) were chosen along with a
dose of OX7-saporin (2.0 micrograms/rat) that produced Purkinje loss equivalent
to the two highest doses of 192-saporin. Groups of Fischer-344 rats were trained
in the multiple choice reaction time task and retested with more complex tasks
after lesioning. They were also tested in the water maze, passive avoidance,
acoustic startle, and open field. The OX7-saporin group exhibited changes in many
tests suggesting hypermotility and sensory deficits. The 192-saporin groups
differed from the OX7-saporin group when they displayed deficits in multiple
choice reaction time tasks in which novel challenges were introduced, including
sessions with a noise distractor, shortened and lengthened intertrial intervals,
and use of nine instead of five sources of light stimulus. The 192-saporin groups
showed no impairment in the other tasks. The cholinergic basal forebrain lesion
may mask some of the effects of cerebellar damage up to a threshold after which
effects of Purkinje cell loss predominate when 192-saporin is administered
intraventricularly.
PMID- 10196112
TI - Single-molecule imaging of human insulin receptor ectodomain and its Fab
complexes.
AB - The insulin receptor (IR) is a four-chain, transmembrane dimer held together by
disulfide bonds. To gain information about the molecular envelope and the
organization of its domains, single-molecule images of the IR ectodomain and its
complexes with three Fabs have been analyzed by electron microscopy. The data
indicate that the IR ectodomain resembles a U-shaped prism of approximate
dimensions 90 x 80 x 120 A. The width of the cleft (assumed membrane-distal)
between the two side arms is sufficient to accommodate ligand. Fab 83-7, which
recognizes the cys-rich region of IR, bound halfway up one end of each side arm
in a diametrically opposite manner, indicating a twofold axis of symmetry normal
to the membrane surface. Fabs 83-14 and 18-44, which have been mapped
respectively to the first fibronectin type III domain (residues 469-592) and
residues 765-770 in the insert domain, bound near the base of the prism at
opposite corners. These images, together with the data from the recently
determined 3D structure of the first three domains of the insulin-like growth
factor type I receptor, suggest that the IR dimer is organized into two layers
with the L1/cys-rich/L2 domains occupying the upper (membrane distal) region of
the U-shaped prism and the fibronectin type III domains and the insert domains
located predominantly in the membrane-proximal region.
PMID- 10196113
TI - Structural studies of a novel germination protease from spores of Bacillus
megaterium.
AB - The amino acid sequence-specific protease (termed GPR) in the bacterium Bacillus
megaterium initiates the rapid degradation of small, acid-soluble spore proteins
during the germination of spores of this organism. GPR is synthesized during
spore formation as an inactive zymogen termed P46, which later autoprocesses to a
smaller active form termed P41, which acts during spore germination. However, GPR
exhibits no obvious mechanistic or amino acid sequence similarity to any of the
known classes of proteases. To initiate the determination of the mechanisms of
P46 to P41 conversion, P46 inactivity, and P41 catalysis, B. megaterium GPR has
been overexpressed in Escherichia coli and purified to homogeneity by anion
exchange and size exclusion chromatography, and crystals of both P46 and P41 have
been obtained by the vapor diffusion method. P46 crystals diffracted x rays to
3.5 A but the crystals of P41 diffracted x rays to only 6.5 A. A native x-ray
diffraction data set of P46 has been collected; the unit cell parameters are a =
b = 76.8, c = 313.1 A, alpha = beta = gamma = 90 degrees; the space group is
tetragonal P41212 or P43212. The asymmetric unit contains two monomeric molecules
with a crystal volume per unit protein mass of 2. 85 A3/Da and a solvent content
of about 57%. An isomorphous heavy atom derivative data set has also been
obtained for P46 crystals with potassium dicyanoaurate (I).
PMID- 10196114
TI - Effects of surface-bound water and surface stereochemistry on cell adhesion to
crystal surfaces.
AB - Crystals of calcium-(R,S)-tartrate trihydrate were used as adhesion substrates
(for A6 epithelial cells), to study specific stages in cell adhesion. Events such
as surface recognition, cell attachment, spreading, motility, cell-cell
aggregation, and cell penetration into the crystal bulk are all shown to depend
on the molecular structure of the various crystal faces. These crystals exhibit
three chemically equivalent, yet structurally distinct, faces. On the {100}, a
layered surface exposing bound water, the cells attach, are motile, and tend to
form multicellular aggregates, but do not spread and do not form focal contacts.
Following prolonged incubation, single cells attached to the {100} surface
undergo apoptosis, while those interacting with other cells are rescued.
Macroscopic spiral dislocations emerging on the {100} face of the crystal are
highly adhesive for cells. Cells attached to these sites develop long protrusions
that penetrate into the crystal. The {011} faces expose mainly hydroxyls attached
to the chiral carbons. The cells interact extensively with these faces, are
immobilized, do not spread, do not form focal contacts, and subsequently die. The
faces belonging to the {0kl}? family are characterized by molecular and
topographical steps. The cells attach to these faces, spread, and form focal
contacts and stress fibers. Thus the molecular character of the crystal surfaces,
including the presence of bound water, the exposure of determinants that promote
rapid surface recognition, and the effective association with extracellular
adhesive proteins, affect the patterns of cell adhesive behavior and fate.
PMID- 10196115
TI - Atomic force microscopy study of tooth surfaces.
AB - Atomic force microscopy (AFM) was used to study tooth surfaces in order to
compare the pattern of particle distribution in the outermost layer of the tooth
surfaces. Human teeth and teeth from a rodent (Golden hamster), from a fish
(piranha), and from a grazing mollusk (chiton) with distinct feeding habits were
analyzed in terms of particle arrangement, packing, and size distribution.
Scanning electron microscopy and transmission electron microscopy were used for
comparison. It was found that AFM gives high-contrast, high-resolution images and
is an important tool as a source of complementary and/or new structural
information. All teeth were cleaned and some were etched with acidic solutions
before analysis. It was observed that human enamel (permanent teeth) presents
particles tightly packed in the outer surface, whereas enamel from the hamster
(continuously growing teeth) shows particles of less dense packing. The piranha
teeth have a thin cuticle covering the long apatite crystals of the underlying
enameloid. This cuticle has a rough surface of particles that have a globular
appearance after the brief acidic treatment. The similar appearance of the in
vivo naturally etched tooth surface suggests that the pattern of globule
distribution may be due to the presence of an organic material. Elemental
analysis of this cuticle indicated that calcium, phosphorus, and iron are the
main components of the structure while electron microdiffraction of pulverized
cuticle particles showed a pattern consistent with hydroxyapatite. The chiton
mineralized tooth cusp had a smooth surface in an unabraded region and a very
rough structure with the magnetite crystals (already known to make part of the
structure) protruding from the surface. It was concluded that the structures
analyzed are optimized for efficiency in feeding mechanism and life span of the
teeth.
PMID- 10196116
TI - Cellular control over spicule formation in sea urchin embryos: A structural
approach.
AB - The spicules of the sea urchin embryo form in intracellular membrane-delineated
compartments. Each spicule is composed of a single crystal of calcite and
amorphous calcium carbonate. The latter transforms with time into calcite by
overgrowth of the preexisting crystal. Relationships between the membrane
surrounding the spiculogenic compartment and the spicule mineral phase were
studied in the transmission electron microscope (TEM) using freeze-fracture. In
all the replicas observed the spicules were tightly surrounded by the membrane.
Furthermore, a variety of structures that are related to the material exchange
process across the membrane were observed. The spiculogenic cells were separated
from other cell types of the embryo, frozen, and freeze-dried on the TEM grids.
The contents of electron-dense granules in the spiculogenic cells were shown by
electron diffraction to be composed of amorphous calcium carbonate. These
observations are consistent with the notion that the amorphous calcium carbonate
containing granules contain the precursor mineral phase for spicule formation and
that the membrane surrounding the forming spicule is involved both in transport
of material and in controlling spicule mineralization.
PMID- 10196118
TI - Reconstitution of detergent-solubilized Na,K-ATPase and formation of two
dimensional crystals.
AB - Very pure, detergent-solubilized Na,K-ATPase from dog or lamb kidneys has been
successfully reconstituted at high protein-to-lipid weight ratios. Studies have
been conducted to establish the orientation of the Na,K-ATPase molecules in the
reconstituted membranes and to assess the functional activity and the
conformational state of the reconstituted enzyme. Results indicate that
reincorporation of the Na,K-ATPase molecules in the lipid bilayer is
unidirectional and that the reconstituted enzyme retains its functional and
structural integrity. Two-dimensional crystals have been induced in these
preparations by vanadate ions. The arrays, with a dimeric structure in the unit
cell, have a morphology similar to that of the crystals that had previously
formed in the native membranes. Filtered images show that in projection, the
molecule had an asymmetrical mass distribution, which at the resolution of 2.5 nm
is identical to that of the earlier crystals. These sheets, although small,
represent the first crystals of Na, K-ATPase to be formed by reconstitution. We
expect that optimization of the reconstitution and crystallization parameters
will lead to larger and better-ordered sheets, suitable for electron
crystallography.
PMID- 10196117
TI - Two-dimensional crystallization of Escherichia coli lactose permease.
AB - A chimeric protein consisting of lactose permease with cytochrome b562 in the
middle cytoplasmic loop and six His residues at the C terminus
(LacY/L6cytb562/417H6 or "red permease") was overexpressed in Escherichia coli
and isolated by nickel affinity chromatography after solubilization with dodecyl
beta,d-maltopyranoside. Red permease was then reconstituted in the presence of
phospholipids, yielding densely packed vesicles and well-ordered two-dimensional
(2D) crystals as shown by electron microscopy of negatively stained specimens.
Single-particle analysis of 16 383 protein particles in densely packed vesicles
reveals a 5.4-nm-long trapeziform protein of 4.1 to 5.1 nm width, with a central
stain-filled indentation. Depending on reconstitution conditions, trigonal and
rectangular crystallographic packing arrangements of these elongated particles
assembled into trimers are observed. The best ordered 2D crystals exhibit a
rectangular unit cell, of dimensions a = 9.9 nm, b = 17.4 nm, that houses two
trimeric complexes. Projection maps calculated to a resolution of 2 nm show that
these crystals consist of two layers.
PMID- 10196119
TI - High-resolution crystals of the HU mutant K38N from Bacillus stearothermophilus.
AB - The DNA-binding protein HU is ubiquitous in the prokaryotic cell. It is a major
protein component of isolated nucleoids and is believed to control the tertiary
structure of prokaryotic DNA. The Bacillus stearothermophilus HU (BstHU) mutants
obtained by mutagenesis have been investigated. Crystallization experiments of
BstHU-K38N (Lys38 is substituted with Asn) resulted in two forms of crystals
suitable for high-resolution x-ray analysis. The first form belongs to the
monoclinic space group C2 with unit-cell dimensions of a = 90.1 A, b = 43.5 A, c
= 63.7 A, and beta = 135.1 degrees, and it diffracts x rays to 1.5-A resolution.
The second form belongs to the tetragonal space group I41 with a = b = 62.6 A and
c = 43.3 A, and it diffracts up to 1.8-A resolution.
PMID- 10196120
TI - Crystallization and preliminary X-ray analysis of active site-inhibited human
coagulation factor VIIa (des-Gla).
AB - Human coagulation factor VIIai that lacks the Gla domain (residues 1-44) has been
prepared, purified, and crystallised. First, recombinant factor VII was activated
to form factor VIIa, the active site was then inhibited with 1,5-dansyl-Glu-Gly
Arg-chloromethyl ketone, and finally the Gla domain was removed by chymotryptic
digestion, yielding factor VIIai (des-Gla). After further purification single
crystals suitable for x-ray analysis were obtained by vapour diffusion. Crystals
of factor VIIai (des-Gla) belong to the tetragonal space group P41212 or P43212
with unit cell dimensions a = b = 94.85 A, c = 114.30 A, contain one molecule per
asymmetric unit, and diffract to 2.3-A resolution when exposed to synchrotron
radiation.
PMID- 10196121
TI - NMR structure of the human oncofoetal fibronectin ED-B domain, a specific marker
for angiogenesis.
AB - BACKGROUND: The process of angiogenesis (i.e. the formation of new blood vessels
from pre-existing ones) is fundamental to physiological processes such as
reproduction, development and repair, as well as to pathological conditions such
as tumor progression, rheumathoid arthritis and ocular disorders. The oncofoetal
ED-B domain, a specific marker of angiogenesis, consists of 91 amino acid
residues that are inserted by alternative splicing into the fibronectin (FN)
molecule. RESULTS: The NMR structure of the ED-B domain is reported and reveals
important differences from other FN type III domains. A comparison of the ED-B
domain with the crystal structure of a four-domain FN fragment shows the novel
features of ED-B to be located in loop regions that are buried at interdomain
interfaces, and which therefore largely determine the global shape of the FN
molecule. The negatively charged amino acids in this highly acidic protein are
uniformly distributed over the molecular surface, with the sole exception of a
solvent-exposed hydrophobic patch that represents a potential specific
recognition site. Epitope mapping with 82 decapeptides that span the ED-B
sequence revealed that three ED-B-specific monoclonal antibodies, which
selectively target newly forming blood vessels in tumor-bearing mice, bind to
adjacent regions on the ED-B surface. CONCLUSIONS: The NMR structure enables the
identification of a large surface area of the ED-B domain that appears to be
accessible in vivo, opening up new diagnostic and therapeutic opportunities.
Furthermore, the mapping of specific monoclonal antibodies to the three
dimensional structure of the ED-B domain, and their use in angiogenesis
inhibition experiments, provides a basis for further investigation of the role of
the ED-B domain in the formation of new blood vessels.
PMID- 10196122
TI - Structural basis of activation and GTP hydrolysis in Rab proteins.
AB - BACKGROUND: Rab proteins comprise a large family of GTPases that regulate vesicle
trafficking. Despite conservation of critical residues involved in nucleotide
binding and hydrolysis, Rab proteins exhibit low sequence identity with other
GTPases, and the structural basis for Rab function remains poorly characterized.
RESULTS: The 2. 0 A crystal structure of GppNHp-bound Rab3A reveals the
structural determinants that stabilize the active conformation and regulate
GTPase activity. The active conformation is stabilized by extensive hydrophobic
contacts between the switch I and switch II regions. Serine residues in the
phosphate-binding loop (P loop) and switch I region mediate unexpected
interactions with the gamma phosphate of GTP that have not been observed in
previous GTPase structures. Residues implicated in the interaction with effectors
and regulatory factors map to a common face of the protein. The electrostatic
potential at the surface of Rab3A indicates a non-uniform distribution of charged
and nonpolar residues. CONCLUSIONS: The major structural determinants of the
active conformation involve residues that are conserved throughout the Rab
family, indicating a common mode of activation. Novel interactions with the gamma
phosphate impose stereochemical constraints on the mechanism of GTP hydrolysis
and provide a structural explanation for the large variation of GTPase activity
within the Rab family. An asymmetric distribution of charged and nonpolar
residues suggests a plausible orientation with respect to vesicle membranes,
positioning predominantly hydrophobic surfaces for interaction with membrane
associated effectors and regulatory factors. Thus, the structure of Rab3A
establishes a framework for understanding the molecular mechanisms underlying the
function of Rab GTPases.
PMID- 10196123
TI - Structure of the vault, a ubiquitous celular component.
AB - BACKGROUND: The vault is a ubiquitous and highly conserved ribonucleoprotein
particle of approximately 13 MDa. This particle has been shown to be upregulated
in certain multidrug-resistant cancer cell lines and to share a protein component
with the telomerase complex. Determination of the structure of the vault was
undertaken to provide a first step towards understanding the role of this
cellular component in normal metabolism and perhaps to shed some light on its
role in mediating drug resistance. RESULTS: Over 1300 particle images were
combined to calculate an approximately 31 A resolution structure of the vault.
Rotational power spectra did not yield a clear symmetry peak, either because of
the thin, smooth walls or inherent flexibility of the vault. Although cyclic
eightfold (C8) symmetry was imposed, the resulting reconstruction may be
partially cylindrically averaged about the eightfold axis. Our results reveal the
vault to be a hollow, barrel-like structure with two protruding caps and an
invaginated waist. CONCLUSIONS: Although the normal cellular function of the
vault is as yet undetermined, the structure of the vault is consistent with
either a role in subcellular transport, as previously suggested, or in
sequestering macromolecular assemblies.
PMID- 10196124
TI - A single-domain antibody fragment in complex with RNase A: non-canonical loop
structures and nanomolar affinity using two CDR loops.
AB - BACKGROUND: Camelid serum contains a large fraction of functional heavy-chain
antibodies - homodimers of heavy chains without light chains. The variable
domains of these heavy-chain antibodies (VHH) have a long complementarity
determining region 3 (CDR3) loop that compensates for the absence of the antigen
binding loops of the variable light chains (VL). In the case of the VHH fragment
cAb-Lys3, part of the 24 amino acid long CDR3 loop protrudes from the antigen
binding surface and inserts into the active-site cleft of its antigen, rendering
cAb-Lys3 a competitive enzyme inhibitor. RESULTS: A dromedary VHH with
specificity for bovine RNase A, cAb-RN05, has a short CDR3 loop of 12 amino acids
and is not a competitive enzyme inhibitor. The structure of the cAb-RN05-RNase A
complex has been solved at 2.8 A. The VHH scaffold architecture is close to that
of a human VH (variable heavy chain). The structure of the antigen-binding
hypervariable 1 loop (H1) of both cAb-RN05 and cAb-Lys3 differ from the known
canonical structures; in addition these H1 loops resemble each other. The CDR3
provides an antigen-binding surface and shields the face of the domain that
interacts with VL in conventional antibodies. CONCLUSIONS: VHHs adopt the common
immunoglobulin fold of variable domains, but the antigen-binding loops deviate
from the predicted canonical structure. We define a new canonical structure for
the H1 loop of immunoglobulins, with cAb-RN05 and cAb-Lys3 as reference
structures. This new loop structure might also occur in human or mouse VH
domains. Surprisingly, only two loops are involved in antigen recognition; the
CDR2 does not participate. Nevertheless, the antigen binding occurs with
nanomolar affinities because of a preferential usage of mainchain atoms for
antigen interaction.
PMID- 10196125
TI - Crystal structure of the human p58 killer cell inhibitory receptor (KIR2DL3)
specific for HLA-Cw3-related MHC class I.
AB - BACKGROUND: T cells and natural killer (NK) cells perform complementary roles in
the cellular immune system. T cells identify infected cells directly through
recognition of antigenic peptides that are displayed at the target cell surface
by the classical major histocompatibility complex (MHC) class I molecules. NK
cells monitor the target cell surface for malfunction of this display system,
lysing potentially infected cells that might otherwise evade recognition by the T
cells. Human killer cell inhibitory receptors (KIRs) control this process by
either inhibiting or activating the cytotoxic activity of NK cells via specific
binding to MHC class I molecules on the target cell. RESULTS: We report the
crystal structure of the extracellular region of the human p58 KIR (KIR2DL3),
which is specific for the human MHC class I molecule HLA-Cw3 and related alleles.
The structure shows the predicted topology of two tandem immunoglobulin-like
domains, but comparison with the previously reported structure of the related
receptor KIR2DL1 reveals an unexpected change of 23 degrees in the relative
orientation of these domains. CONCLUSIONS: The altered orientation of the
immunoglobulin-like domains maintains an unusually acute interdomain elbow angle,
which therefore appears to be a distinctive feature of the KIRs. The putative MHC
class I binding site is located on the outer surface of the elbow, spanning both
domains. The unexpected observation that this binding site can be modulated by
differences in the relative domain orientations has implications for the general
mechanism of KIR-MHC class I complex formation.
PMID- 10196126
TI - Crystal structure and functional characterization of OmpK36, the osmoporin of
Klebsiella pneumoniae.
AB - BACKGROUND: Porins are channel-forming membrane proteins that confer solute
permeability to the outer membrane of Gram-negative bacteria. In Escherichia
coli, major nonspecific porins are matrix porin (OmpF) and osmoporin (OmpC),
which show high sequence homology. In response to high osmolarity of the medium,
OmpC is expressed at the expense of OmpF porin. Here, we study osmoporin of the
pathogenic Klebsiella pneumoniae (OmpK36), which shares 87% sequence identity
with E. coliOmpC in an attempt to establish why osmoporin is best suited to
function at high osmotic pressure. RESULTS: The crystal structure of OmpK36 has
been determined to a resolution of 3.2 A by molecular replacement with the model
of OmpF. The structure of OmpK36 closely resembles that of the search model. The
homotrimeric structure is composed of three hollow 16-stranded antiparallel beta
barrels, each delimiting a separate pore. Most insertions and deletions with
respect to OmpF are found in the loops that protrude towards the cell exterior. A
characteristic ten-residue insertion in loop 4 contributes to the subunit
interface. At the pore constriction, the replacement of an alanine by a tyrosine
residue does not alter the pore profile of OmpK36 in comparison with OmpF because
of the different course of the mainchain. Functionally, as characterized in lipid
bilayers and liposomes, OmpK36 resembles OmpC with decreased conductance and
increased cation selectivity in comparison with OmpF. CONCLUSIONS: The osmoporin
structure suggests that not an altered pore size but an increase in charge
density is the basis for the distinct physico-chemical properties of this porin
that are relevant for its preferential expression at high osmotic strength.
PMID- 10196127
TI - The crystal structure of pyroglutamyl peptidase I from Bacillus amyloliquefaciens
reveals a new structure for a cysteine protease.
AB - BACKGROUND: The N-terminal pyroglutamyl (pGlu) residue of peptide hormones, such
as thyrotropin-releasing hormone (TRH) and luteinizing hormone releasing hormone
(LH-RH), confers resistance to proteolysis by conventional aminopeptidases.
Specialized pyroglutamyl peptidases (PGPs) are able to cleave an N-terminal
pyroglutamyl residue and thus control hormonal signals. Until now, no direct or
homology-based three-dimensional structure was available for any PGP. RESULTS:
The crystal structure of pyroglutamyl peptidase I (PGP-I) from Bacillus
amyloliquefaciens has been determined to 1.6 A resolution. The crystallographic
asymmetric unit of PGP-I is a tetramer of four identical monomers related by
noncrystallographic 222 symmetry. The protein folds into an alpha/beta globular
domain with a hydrophobic core consisting of a twisted beta sheet surrounded by
five alpha helices. The structure allows the function of most of the conserved
residues in the PGP-I family to be identified. The catalytic triad comprises
Cys144, His168 and Glu81. CONCLUSIONS: The catalytic site does not have a
conventional oxyanion hole, although Cys144, the sidechain of Arg91 and the
dipole of an alpha helix could all stabilize a negative charge. The catalytic
site has an S1 pocket lined with conserved hydrophobic residues to accommodate
the pyroglutamyl residue. Aside from the S1 pocket, there is no clearly defined
mainchain substrate-binding region, consistent with the lack of substrate
specificity. Although the overall structure of PGP-I resembles some other
alpha/beta twisted open-sheet structures, such as purine nucleoside phosphorylase
and cutinase, there are important differences in the location and organization of
the active-site residues. Thus, PGP-I belongs to a new family of cysteine
proteases.
PMID- 10196128
TI - Crystal structures of Bacillus caldovelox arginase in complex with substrate and
inhibitors reveal new insights into activation, inhibition and catalysis in the
arginase superfamily.
AB - BACKGROUND: Arginase is a manganese-dependent enzyme that catalyzes the
hydrolysis of L-arginine to L-ornithine and urea. In ureotelic animals arginase
is the final enzyme of the urea cycle, but in many species it has a wider role
controlling the use of arginine for other metabolic purposes, including the
production of creatine, polyamines, proline and nitric oxide. Arginase activity
is regulated by various small molecules, including the product L-ornithine. The
aim of these structural studies was to test aspects of the catalytic mechanism
and to investigate the structural basis of arginase inhibition. RESULTS: We
report here the crystal structures of arginase from Bacillus caldovelox at pH 5.6
and pH 8.5, and of binary complexes of the enzyme with L-arginine, L-ornithine
and L-lysine at pH 8.5. The arginase monomer comprises a single compact
alpha/beta domain that further associates into a hexameric quaternary structure.
The binary complexes reveal a common mode of ligand binding, which places the
substrate adjacent to the dimanganese centre. We also observe a conformational
change that impacts on the active site and is coupled with the occupancy of an
external site by guanidine or arginine. CONCLUSIONS: The structures reported here
clarify aspects of the active site and indicate key features of the catalytic
mechanism, including substrate coordination to one of the manganese ions and an
orientational role for a neighboring histidine residue. Stereospecificity for L
amino acids is found to depend on their precise recognition at the active-site
rim. Identification of a second arginine-binding site, remote from the active
site, and associated conformational changes lead us to propose a regulatory role
for this site in substrate hydrolysis.
PMID- 10196129
TI - Structure of the PH domain from Bruton's tyrosine kinase in complex with inositol
1,3,4,5-tetrakisphosphate.
AB - BACKGROUND: The activity of Bruton's tyrosine kinase (Btk) is important for the
maturation of B cells. A variety of point mutations in this enzyme result in a
severe human immunodeficiency known as X-linked agammaglobulinemia (XLA). Btk
contains a pleckstrin-homology (PH) domain that specifically binds
phosphatidylinositol 3,4,5-trisphosphate and, hence, responds to signalling via
phosphatidylinositol 3-kinase. Point mutations in the PH domain might abolish
membrane binding, preventing signalling via Btk. RESULTS: We have determined the
crystal structures of the wild-type PH domain and a gain-of-function mutant E41K
in complex with D-myo-inositol 1,3,4,5-tetra-kisphosphate (Ins (1,3,4,5)P4). The
inositol Ins (1,3,4,5)P4 binds to a site that is similar to the inositol 1,4,5
trisphosphate binding site in the PH domain of phospholipase C-delta. A second
Ins (1,3,4,5)P4 molecule is associated with the domain of the E41K mutant,
suggesting a mechanism for its constitutive interaction with membrane. The
affinities of Ins (1,3,4,5)P4 to the wild type (Kd = 40 nM), and several XLA
causing mutants have been measured using isothermal titration calorimetry.
CONCLUSIONS: Our data provide an explanation for the specificity and high
affinity of the interaction with phosphatidylinositol 3,4,5-trisphosphate and
lead to a classification of the XLA mutations that reside in the Btk PH domain.
Mis-sense mutations that do not simply destabilize the PH fold either directly
affect the interaction with the phosphates of the lipid head group or change
electrostatic properties of the lipid-binding site. One point mutation (Q127H)
cannot be explained by these facts, suggesting that the PH domain of Btk carries
an additional function such as interaction with a Galpha protein.
PMID- 10196131
TI - Chloroplast NADP-malate dehydrogenase: structural basis of light-dependent
regulation of activity by thiol oxidation and reduction.
AB - BACKGROUND: NADP-dependent malate dehydrogenase (EC 1.1.1.82) is a light
activated chloroplast enzyme that functions in the C4 pathway of photosynthesis.
The light regulation is believed to be mediated in vivo by thioredoxin-catalyzed
reduction and re-oxidation of cystine residues. The rates of reversible
activation and inactivation of the enzyme are strongly influenced by the coenzyme
substrates that seem to ultimately determine the steady-state extent of
activation in vivo. RESULTS: The X-ray structure of the inactive, oxidized enzyme
was determined at 2.8 A resolution. The core structure is homologous to AND
dependent malate dehydrogenases. Two surface-exposed and thioredoxin-accessible
disulfide bonds are present, one in the N-terminal extension and the other in the
C-terminal extension. The C-terminal peptide of the inactive, oxidized enzyme is
constrained by its disulfide bond to fold into the active site over NADP+,
hydrogen bonding to the catalytic His225 as well as obstructing access of the C4
acid substrate. Two loops flanking the active site, termed the Arg2 and Trp
loops, that contain the C4 acid substrate binding residues are prevented from
closing by the C-terminal extension. CONCLUSIONS: The structure explains the role
of the C-terminal extension in inhibiting activity. The negative C terminus will
interact more strongly with the positively charged nicotinamide of NADP+ than
NADPH, explaining why the coenzyme-binding affinities of the enzyme differ so
markedly from those of all other homologous alpha-hydroxy acid dehydrogenases.
NADP+ may also slow dissociation of the C terminus upon reduction, providing a
mechanism for the inhibition of activation by NADP+ but not NADPH.
PMID- 10196130
TI - ATP synthase: two motors, two fuels.
AB - FoF1 ATPase is the universal protein responsible for ATP synthesis. The enzyme
comprises two reversible rotary motors: Fo is either an ion 'turbine' or an ion
pump, and F1 is either a hydrolysis motor or an ATP synthesizer. Recent
biophysical and biochemical studies have helped to elucidate the operating
principles for both motors.
PMID- 10196132
TI - Who solved the protein folding problem?
AB - For the third time, techniques for the prediction of three-dimensional structures
of proteins were critically assessed in a worldwide blind test. Steady progress
is undeniable. How did this happen and what are the implications?
PMID- 10196133
TI - The role of phosphatases in inositol signaling reactions.
PMID- 10196134
TI - Crystal structure of the sulfotransferase domain of human heparan sulfate N
deacetylase/ N-sulfotransferase 1.
AB - Heparan sulfate N-deacetylase/N-sulfotransferase (HSNST) catalyzes the first and
obligatory step in the biosynthesis of heparan sulfates and heparin. The crystal
structure of the sulfotransferase domain (NST1) of human HSNST-1 has been
determined at 2.3-A resolution in a binary complex with 3'-phosphoadenosine 5'
phosphate (PAP). NST1 is approximately spherical with an open cleft, and consists
of a single alpha/beta fold with a central five-stranded parallel beta-sheet and
a three-stranded anti-parallel beta-sheet bearing an interstrand disulfide bond.
The structural regions alpha1, alpha6, beta1, beta7, 5'-phosphosulfate binding
loop (between beta1 and alpha1), and a random coil (between beta8 and alpha13)
constitute the PAP binding site of NST1. The alpha6 and random coil (between
beta2 and alpha2), which form an open cleft near the 5'-phosphate of the PAP
molecule, may provide interactions for substrate binding. The conserved residue
Lys-614 is in position to form a hydrogen bond with the bridge oxygen of the 5'
phosphate.
PMID- 10196135
TI - Identification of NSF as a beta-arrestin1-binding protein. Implications for beta2
adrenergic receptor regulation.
AB - Previous studies have demonstrated that beta-arrestin1 serves to target G protein
coupled receptors for internalization via clathrin-coated pits and that its
endocytic function is regulated by dephosphorylation at the plasma membrane.
Using the yeast two-hybrid system, we have identified a novel beta-arrestin1
binding protein, NSF (N-ethylmaleimide-sensitive fusion protein), an ATPase
essential for many intracellular transport reactions. We demonstrate that
purified recombinant beta-arrestin1 and NSF interact in vitro and that these
proteins can be coimmunoprecipitated from cells. beta-Arrestin1-NSF complex
formation exhibits a conformational dependence with beta-arrestin1 preferentially
interacting with the ATP bound form of NSF. In contrast to the beta-arrestin1
clathrin interaction, however, the phosphorylation state of beta-arrestin1 does
not affect NSF binding. Functionally, overexpression of NSF in HEK 293 cells
significantly enhances agonist-mediated beta2-adrenergic receptor (beta2-AR)
internalization. Furthermore, when coexpressed with a beta-arrestin1 mutant
(betaarr1S412D) that mimics a constitutively phosphorylated form of beta
arrestin1 and that acts as a dominant negative with regards to beta2-AR
internalization, NSF rescues the betaarr1S412D-mediated inhibition of beta2-AR
internalization. The demonstration of beta-arrestin1-NSF complex formation and
the functional consequences of NSF overexpression suggest a hitherto
unappreciated role for NSF in facilitating clathrin coat-mediated G protein
coupled receptor internalization.
PMID- 10196136
TI - Phosphorylation of axin, a Wnt signal negative regulator, by glycogen synthase
kinase-3beta regulates its stability.
AB - Axin forms a complex with glycogen synthase kinase-3beta (GSK-3beta) and beta
catenin and promotes GSK-3beta-dependent phosphorylation of beta-catenin, thereby
stimulating the degradation of beta-catenin. Because GSK-3beta also
phosphorylates Axin in the complex, the physiological significance of the
phosphorylation of Axin was examined. Treatment of COS cells with LiCl, a GSK
3beta inhibitor, and okadaic acid, a protein phosphatase inhibitor, decreased and
increased, respectively, the cellular protein level of Axin. Pulse-chase analyses
showed that the phosphorylated form of Axin was more stable than the
unphosphorylated form and that an Axin mutant, in which the possible
phosphorylation sites for GSK-3beta were mutated, exhibited a shorter half-life
than wild type Axin. Dvl-1, which was genetically shown to function upstream of
GSK-3beta, inhibited the phosphorylation of Axin by GSK-3beta in vitro.
Furthermore, Wnt-3a-containing conditioned medium down-regulated Axin and
accumulated beta-catenin in L cells and expression of Dvl-1(DeltaPDZ), in which
the PDZ domain was deleted, suppressed this action of Wnt-3a. These results
suggest that the phosphorylation of Axin is important for the regulation of its
stability and that Wnt down-regulates Axin through Dvl.
PMID- 10196137
TI - Interaction of heterotrimeric G protein Galphao with Purkinje cell protein-2.
Evidence for a novel nucleotide exchange factor.
AB - The heterotrimeric G protein Galphao is ubiquitously expressed throughout the
central nervous system, but many of its functions remain to be defined. To search
for novel proteins that interact with Galphao, a mouse brain library was screened
using the yeast two-hybrid interaction system. Pcp2 (Purkinje cell protein-2) was
identified as a partner for Galphao in this system. Pcp2 is expressed in
cerebellar Purkinje cells and retinal bipolar neurons, two locations where
Galphao is also expressed. Pcp2 was first identified as a candidate gene to
explain Purkinje cell degeneration in pcd mice (Nordquist, D. T., Kozak, C. A.,
and Orr, H. T. (1988) J. Neurosci. 8, 4780-4789), but its function remains
unknown as Pcp2 knockout mice are normal (Mohn, A. R., Feddersen, R. M., Nguyen,
M. S., and Koller, B. H. (1997) Mol. Cell. Neurosci. 9, 63-76). Galphao and Pcp2
binding was confirmed in vitro using glutathione S-transferase-Pcp2 fusion
proteins and in vitro translated [35S]methionine-labeled Galphao. In addition,
when Galphao and Pcp2 were cotransfected into COS cells, Galphao was detected in
immunoprecipitates of Pcp2. To determine whether Pcp2 could modulate Galphao
function, kinetic constants kcat and koff of bovine brain Galphao were determined
in the presence and absence of Pcp2. Pcp2 stimulates GDP release from Galphao
more than 5-fold without affecting kcat. These findings define a novel nucleotide
exchange function for Pcp2 and suggest that the interaction between Pcp2 and
Galphao is important to Purkinje cell function.
PMID- 10196138
TI - Toll-like receptor-4 mediates lipopolysaccharide-induced signal transduction.
AB - TLR4 is a member of the recently identified Toll-like receptor family of proteins
and has been putatively identified as Lps, the gene necessary for potent
responses to lipopolysaccharide in mammals. In order to determine whether TLR4 is
involved in lipopolysaccharide-induced activation of the nuclear factor-kappaB
(NF-kappaB) pathway, HEK 293 cells were transiently transfected with human TLR4
cDNA and an NF-kappaB-dependent luciferase reporter plasmid followed by
stimulation with lipopolysaccharide/CD14 complexes. The results demonstrate that
lipopolysaccharide stimulates NF-kappaB-mediated gene expression in cells
transfected with the TLR4 gene in a dose- and time-dependent fashion.
Furthermore, E5531, a lipopolysaccharide antagonist, blocked TLR4-mediated
transgene activation in a dose-dependent manner (IC50 approximately 30 nM). These
data demonstrate that TLR4 is involved in lipopolysaccharide signaling and serves
as a cell-surface co-receptor for CD14, leading to lipopolysaccharide-mediated NF
kappaB activation and subsequent cellular events.
PMID- 10196139
TI - Trimethylamine N-oxide-induced cooperative folding of an intrinsically unfolded
transcription-activating fragment of human glucocorticoid receptor.
AB - A number of biologically important proteins or protein domains identified
recently are fully or partially unstructured (unfolded). Methods that allow
studies of the propensity of such proteins to fold naturally are valuable. The
traditional biophysical approaches using alcohols to drive alpha-helix formation
raise serious questions of the relevance of alcohol-induced structure to the
biologically important conformations. Recently we illustrated the extraordinary
capability of the naturally occurring solute, trimethylamine N-oxide (TMAO), to
force two unfolded proteins to fold to native-like species with significant
functional activity. In the present work we apply this technique to recombinant
human glucocorticoid receptor fragments consisting of residues 1-500 and residues
77-262. CD and fluorescence spectroscopy showed that both were largely disordered
in aqueous solution. TMAO induced a condensed structure in the large fragment,
indicated by the substantial enhancement in intrinsic fluorescence and blue shift
of fluorescent maxima. CD spectroscopy demonstrated that the TMAO-induced
structure is different from the alpha-helix-rich conformation driven by
trifluoroethanol (TFE). In contrast to TFE, the conformational transition of the
1-500 fragment induced by TMAO is cooperative, a condition characteristic of
proteins with unique structures.
PMID- 10196140
TI - Interaction of human macrophage C-type lectin with O-linked N-acetylgalactosamine
residues on mucin glycopeptides.
AB - A fluorescein-labeled synthetic peptide, PTTTPITTTTK, was converted into O
glycosylated glycopeptides with various numbers of attached N-acetyl-D
galactosamines (GalNAcs) by in vitro glycosylation with UDP-GalNAc and a
microsomal fraction of LS174T human colon carcinoma cells. Glycopeptides with 1,
3, 5, and 6 GalNAc residues (G1, G3, G5, and G6) were obtained, and their sizes
were confirmed by matrix-assisted laser desorption ionization time-of-flight mass
spectrometry. Their sequences were determined by a peptide sequencer to be
PTTTGalNAcPITTTTK for G1, PTGalNAcTTPITGalNAcTGalNAcTTK for G3,
PTTGalNAcTGalNAcPITGalNAcTGalNAcTGalNAcTK for G5, and
PTGalNAcTGalNAcTGalNAcPITGalNAcTGalNAcTGalNAcTK for G6. A calcium-type human
macrophage lectin (HML) was prepared in a recombinant form, and its interaction
with these glycopeptides was investigated by surface plasmon resonance (SPR)
spectroscopy and fluorescence polarization. The affinity of recombinant HML
(rHML) for immobilized glycopeptides increased, as revealed by SPR, in parallel
with the number of GalNAc. The highest affinity was obtained when the G6-peptide
was immobilized at high density. Fluorescence polarization equilibrium-binding
assays also revealed that the affinity of rHML for soluble gly-copeptides
increased, depending on the number of attached GalNAcs. Carbohydrate recognition
domain (CRD) fragments of HML were prepared, and their affinity for these four
glycopeptides was also determined, this affinity was apparently lower than that
of rHML. Affinity constants of rHML for the G3- and G5-peptides were 11- and 38
fold higher, respectively, than for the G1-peptide, whereas those of CRD
fragments were only 2- and 6-fold higher, respectively. A chemical cross-linking
study revealed that rHML but not recombinant CRD forms trimers in an aqueous
solution. Thus, preferential binding of densely glycosylated O-linked
glycopeptides should be due to the trimer formation of rHML.
PMID- 10196141
TI - The vacuolar H+-ATPase of lemon fruits is regulated by variable H+/ATP coupling
and slip.
AB - Lemon fruit tonoplasts, unlike those of seedling epicotyls, contain nitrate
insensitive H+-ATPase activity (Muller, M. L., Irkens-Kiesecker, U., Rubinstein,
B., and Taiz, L. (1996) J. Biol. Chem. 271, 1916-1924). However, the degree of
nitrate-insensitivity fluctuates during the course of the year with a seasonal
frequency. Nitrate uncouples H+ pumping from ATP hydrolysis both in epicotyls and
in nitrate-sensitive fruit V-ATPases. Neither bafilomycin nor oxidation cause
uncoupling. The initial rate H+/ATP coupling ratios of epicotyl and the nitrate
sensitive fruit proton pumping activities are the same. However, the H+/ATP
coupling ratio of the nitrate-insensitive fruit H+ pumping activity is lower than
that of nitrate-sensitive and epicotyl V-ATPases. Several properties of the
nitrate-insensitive H+-ATPase of the fruit indicate that it is a modified V
ATPase rather than a P-ATPase: 1) insensitivity to low concentrations of
vanadate; 2) it is initially strongly uncoupled by nitrate, but regains coupling
as catalysis proceeds; 3) both the nitrate-sensitive and nitrate-insensitive
fruit H+-pumps have identical Km values for MgATP, and show similar pH-dependent
slip and proton leakage rates. We conclude that the ability of the juice sac V
ATPase to build up steep pH gradients involves three factors: variable coupling,
i.e. the ability to regain coupling under conditions that initially induce
uncoupling; a low pH-dependent slip rate; the low proton permeability of the
membrane.
PMID- 10196142
TI - Target cell susceptibility to lysis by human natural killer cells is augmented by
alpha(1,3)-galactosyltransferase and reduced by alpha(1, 2)-fucosyltransferase.
AB - Susceptibility of porcine endothelial cells to human natural killer (NK) cell
lysis was found to reflect surface expression of ligands containing Gal
alpha(1,3)Gal beta(1,4)GlcNAc [corrected], the principal antigen on porcine
endothelium recognized by xenoreactive human antibodies. Genetically modifying
expression of this epitope on porcine endothelium by transfection with the
alpha(1,2)-fucosyltransferase gene reduced susceptibility to human NK lysis.
These results indicate that surface carbohydrate remodeling profoundly affects
target cell susceptibility to NK lysis, and suggest that successful transgenic
strategies to limit xenograft rejection by NK cells and xenoreactive antibodies
will need to incorporate carbohydrate remodeling.
PMID- 10196143
TI - Critical role for STAT3 in murine pituitary adrenocorticotropin hormone leukemia
inhibitory factor signaling.
AB - Leukemia inhibitory factor (LIF) is a pleiotropic neuroimmune cytokine that
promotes corticotroph cell differentiation and induces proopiomelanocortin (POMC)
mRNA expression and adrenocorticotropin hormone (ACTH) secretion. However,
molecular mechanisms for this induction remain elusive. We therefore developed
ACTH-secreting AtT20 transformants for wild-type or mutated STAT3, a cytokine
signaling molecule, to address whether STAT3 is a determinant of LIF-mediated
ACTH regulation. We show that these mutants act in a dominant negative manner by
blocking endogenous STAT3 tyrosine phosphorylation or STAT3 DNA binding.
Attenuation of STAT3 activity in the dominant negative AtT20 clones prevented LIF
from promoting transcriptional activation of the POMC promoter (2.1-fold),
whereas this LIF action was enhanced (7.7-fold; p < 0.05) in wild-type STAT3
overexpressing clones in comparison to mock-transfected cells (4.5-fold).
However, wild-type or dominant negative STAT3-overexpressing clones showed
comparable (4-fold) POMC induction after treatment with cyclic adenosine
monophosphate (cAMP), an alternate inducer of POMC transcription, indicating the
STAT3 specificity for LIF signaling. Moreover, dominant negative inactivation of
STAT3 activity resulted in abrogation of LIF-induced POMC mRNA levels and ACTH
secretion, confirming the in vivo role of STAT3 in LIF-mediated corticotroph
action. Chemical or molecular blockade of the mitogen-activated protein kinase
pathway did not affect LIF-mediated corticotroph function. These results indicate
that STAT3 is a critical intrapituitary component of the LIF-mediated
neuroimmunoendocrine interface in corticotroph cells.
PMID- 10196144
TI - Dominant negative isoform of rat norepinephrine transporter produced by
alternative RNA splicing.
AB - We have cloned from rat brain a family of alternatively spliced cDNAs from a
single gene, which encodes a norepinephrine transporter (NET) having variations
at the 3'-region including both coding and noncoding regions. This produces two
transporter isoforms, rNETa and rNETb, which differ at their COOH termini. The
rNETa isoform reveals a COOH terminus homologous to human NET and transports
norepinephrine. In contrast, rNETb revealed no detectable transport function but
reduced functional expression of rNETa when both isoforms were expressed in the
same cell. Thus, rNETb potentially functions as a dominant negative inhibitor of
rNETa activity. Co-expression of rNETb with a gamma-aminobutyric acid transporter
(rGAT1), a serotonin transporter (rSERT), and a dopamine transporter (rDAT)
reduced their transport activity. No reduction was found with the
glutamate/aspartate transporter (rGLAST). Alternative RNA splicing of NET
suggests a novel mechanism for the regulation of synaptic transmission.
PMID- 10196145
TI - mRNAs encoding a von Ebner's-like protein and the Huntington disease protein are
induced in rat male germ cells by Sertoli cells.
AB - The success of spermatogenesis is dependent upon closely coordinated interactions
between Sertoli cells and germ cells. To identify specific molecules that mediate
interactions between somatic cells and germ cells in the rat testis, Sertoli cell
germ cell co-cultures and mRNA differential display were used. Two cDNAs, clone 1
(660 nucleotides) and clone 2 (390 nucleotides) were up-regulated when Sertoli
cells were co-cultured with pachytene spermatocytes or round spermatids. Northern
blot analyses confirmed the differential display expression patterns. Sequence
analyses indicated that clone 1 was similar to a von Ebner's gland protein (87%
at the nucleotide level and 80% at the amino acid level) and clone 2 was
identical to a region of the Huntington disease protein. The von Ebner's-like
protein mRNA was induced after 4 h of co-culture, while the Huntington disease
protein required 18 h of co-culture for expression. The von Ebner's-like protein
was induced in germ cells by a secreted Sertoli cell factor(s) smaller than 10
kDa that is sensitive to freezing and thawing or boiling. The Huntington disease
protein was induced in germ cells by a Sertoli cell secreted factor(s) larger
than 10 kDa which survives freezing and thawing, but is inactivated by boiling.
PMID- 10196146
TI - Specific isoforms of actin-binding proteins on distinct populations of Golgi
derived vesicles.
AB - Golgi membranes and Golgi-derived vesicles are associated with multiple
cytoskeletal proteins and motors, the diversity and distribution of which have
not yet been defined. Carrier vesicles were separated from Golgi membranes, using
an in vitro budding assay, and different populations of vesicles were separated
using sucrose density gradients. Three main populations of vesicles labeled with
beta-COP, gamma-adaptin, or p200/myosin II were separated and analyzed for the
presence of actin/actin-binding proteins. beta-Actin was bound to Golgi cisternae
and to all populations of newly budded vesicles. Centractin was selectively
associated with vesicles co-distributing with beta-COP-vesicles, while
p200/myosin II (non-muscle myosin IIA) and non-muscle myosin IIB were found on
different vesicle populations. Isoforms of the Tm5 tropomyosins were found on
selected Golgi-derived vesicles, while other Tm isoforms did not colocalize with
Tm5 indicating the association of specialized actin filaments with Golgi-derived
vesicles. Golgi-derived vesicles were shown to bind to F-actin polymerized from
cytosol with Jasplakinolide. Thus, newly budded, coated vesicles derived from
Golgi membranes can bind to actin and are customized for differential
interactions with microfilaments by the presence of selective arrays of actin
binding proteins.
PMID- 10196147
TI - Activity and stability of recombinant bifunctional rearranged and monofunctional
domains of ATP-sulfurylase and adenosine 5'-phosphosulfate kinase.
AB - Murine adenosine 3'-phosphate 5'-phosphosulfate (PAPS) synthetase consists of a
COOH-terminal ATP-sulfurylase domain covalently linked through a nonhomologous
intervening sequence to an NH2-terminal adenosine 5'-phosphosulfate (APS) kinase
domain forming a bifunctional fused protein. Possible advantages of
bifunctionality were probed by separating the domains on the cDNA level and
expressing them as monofunctional proteins. Expressed protein generated from the
ATP-sulfurylase domain alone was fully active in both the forward and reverse
sulfurylase assays. APS kinase-only recombinants exhibited no kinase activity.
However, extension of the kinase domain at the COOH terminus by inclusion of the
36 residue linker region restored kinase activity. An equimolar mixture of the
two monofunctional enzymes catalyzed the overall reaction (synthesis of PAPS from
ATP + SO42-) comparably to the fused bifunctional enzyme. The importance of the
domain order and organization was demonstrated by generation of a series of
rearranged recombinants in which the order of the two active domains was reversed
or altered relative to the linker region. The critical role of the linker region
was established by generation of recombinants that had the linker deleted or
rearranged relative to the two active domains. The intrinsic stability of the
various recombinants was also investigated by measuring enzyme deactivation as a
function of time of incubation at 25 or 37 degrees C. The expressed
monofunctional ATP-sulfurylase, which was initially fully active, was unstable
compared with the fused bifunctional wild type enzyme, decaying with a t1/2 of 10
min at 37 degrees C. Progressive extension by addition of kinase sequence at the
NH2-terminal side of the sulfurylase recombinant eventually stabilized
sulfurylase activity. Sulfurylase activity was significantly destabilized in a
time-dependent manner in the rearranged proteins as well. In contrast, no
significant deactivation of any truncated kinase-containing recombinants or
misordered kinase recombinants was observed at either temperature. It would
therefore appear that fusion of the two enzymes enhances the intrinsic stability
of the sulfurylase only.
PMID- 10196148
TI - Porcine pancreatic phospholipase A2 stimulates secretin release from secretin
producing cells.
AB - We have isolated, from canine pancreatic juice, two 14-kDa proteins with secretin
releasing activity that had N-terminal sequence homology with canine pancreatic
phospholipase A2 (PLA2). In this study we have obtained evidence that secretin
releasing activity is an intrinsic property of pancreatic PLA2. Porcine
pancreatic PLA2 from Sigma or Boehringer Mannheim was fractionated into several
peaks by reverse phase high performance liquid chromatography. They were tested
for stimulation of secretin release from murine neuroendocrine intestinal tumor
cell line STC-1 and secretin cells enriched mucosal cell preparations isolated
from rat upper small intestine. Each enzyme preparation was found to contain
several components of secretin-releasing activity. Each bioactive fraction was
purified to homogeneity by rechromatography and then subjected to mass spectral
analysis and assays of PLA2 and secretin-releasing activities. It was found that
the fraction with highest enzymatic activity also had the highest secretin
releasing activity and the same Mr as porcine pancreatic PLA2. Moreover, it also
had the same N-terminal amino acid sequence (up to 30 residues determined) as
that of porcine pancreatic PLA2, suggesting that it was identical to the enzyme.
Purified porcine pancreatic PLA2 also stimulated secretin release concentration
dependently from both STC-1 cells and a mucosal cell preparation enriched in
secretin-containing endocrine cells isolated from rat duodenum. Abolishment of
the enzymatic activity by pretreatment with bromophenacyl bromide did not affect
its secretin-releasing activity. The stimulatory effect of purified pancreatic
PLA2 on secretin secretion from STC-1 cells was inhibited by an L-type Ca2+
channel blocker, by down-regulation of protein kinase C or by pretreatment of the
cell with pertussis toxin. It is concluded that porcine pancreatic PLA2 possesses
an intrinsic secretin-releasing activity that was independent of its enzymatic
activity. This action is pertussis toxin-sensitive and is in part dependent on
Ca2+ influx through the L-type channel and activation of protein kinase C.
PMID- 10196149
TI - Cleavage of zetaPKC but not lambda/iotaPKC by caspase-3 during UV-induced
apoptosis.
AB - The stimulation of caspases is a critical event in apoptotic cell death. Several
kinases critically involved in cell proliferation pathways have been shown to be
cleaved by caspase-mediated mechanisms. Thus, the degradation of delta protein
kinase C (PKC) and MEKK-1 by caspase-3 generates activated fragments
corresponding to their catalytic domains, consistent with the observations that
both enzymes are important for apoptosis. In contrast, other kinases reported to
have anti-apoptotic properties, such as Raf-1 and Akt, are inactivated by
proteolytic degradation by the caspase system. Since the atypical PKCs have been
shown to play critical roles in cell survival, in the study reported here we have
addressed the potential degradation of these PKCs by the caspase system in UV
irradiated HeLa cells. Herein we show that although zetaPKC and lambda/iotaPKC
are both inhibited in UV-treated cells, only zetaPKC but not lambda/iotaPKC is
cleaved by a caspase-mediated process. This cleavage generates a fragment that
corresponds to its catalytic domain that is enzymatically inactive. The sequence
where caspase-3 cleaves zetaPKC was mapped, and a mutant resistant to degradation
was shown to protect cells from apoptosis more efficiently than the wild-type
enzyme.
PMID- 10196150
TI - Oxidation of ultrafast radical clock substrate probes by the soluble methane
monooxygenase from Methylococcus capsulatus (Bath).
AB - Radical clock substrate probes were used to assess the viability of a discrete
substrate radical species in the mechanism of hydrocarbon oxidation by the
soluble methane monooxygenase (sMMO) from Methylococcus capsulatus (Bath). New
substituted cyclopropane probes were used with very fast ring-opening rate
constants and other desirable attributes, such as the ability to discriminate
between radical and cationic intermediates. Oxidation of these substrates by a
reconstituted sMMO system resulted in no rearranged products, allowing an upper
limit of 150 fs to be placed on the lifetime of a putative radical species. This
limit strongly suggests that there is no such substrate radical intermediate. The
two enantiomers of trans-1-methyl-2-phenyl-cyclopropane were prepared, and the
regioselectivity of their oxidation to the corresponding cyclopropylmethanol and
cyclopropylphenol products was determined. The results are consistent with
selective orientation of the two enantiomeric substrates in the hydrophobic
cavity at the active site of sMMO, specific models for which were examined by
molecular modeling.
PMID- 10196151
TI - The conserved lysine 860 in the additional fatty-acylation site of Bordetella
pertussis adenylate cyclase is crucial for toxin function independently of its
acylation status.
AB - The Bordetella pertussis RTX (repeat in toxin family protein) adenylate cyclase
toxin-hemolysin (ACT) acquires biological activity upon a single amide-linked
palmitoylation of the epsilon-amino group of lysine 983 (Lys983) by the accessory
fatty-acyltransferase CyaC. However, an additional conserved RTX acylation site
can be identified in ACT at lysine 860 (Lys860), and this residue becomes
palmitoylated when recombinant ACT (r-Ec-ACT) is produced together with CyaC in
Escherichia coli K12. We have eliminated this additional acylation site by
replacing Lys860 of ACT with arginine, leucine, and cysteine residues. Two
dimensional gel electrophoresis and microcapillary high performance liquid
chromatography/tandem mass spectrometric analyses of mutant proteins confirmed
that the two sites are acylated independently in vivo and that mutations of
Lys860 did not affect the quantitative acylation of Lys983 by palmitoyl (C16:0)
and palmitoleil (cis Delta9 C16:1) fatty-acyl groups. Nevertheless, even the most
conservative substitution of lysine 860 by an arginine residue caused a 10-fold
decrease of toxin activity. This resulted from a 5-fold reduction of cell
association capacity and a further 2-fold reduction in cell penetration
efficiency of the membrane-bound K860R toxin. These results suggest that lysine
860 plays by itself a crucial structural role in membrane insertion and
translocation of the toxin, independently of its acylation status.
PMID- 10196152
TI - Cosuppression of photosystem I subunit PSI-H in Arabidopsis thaliana. Efficient
electron transfer and stability of photosystem I is dependent upon the PSI-H
subunit.
AB - PSI-H is an intrinsic membrane protein of 10 kDa that is a subunit of photosystem
I (PSI). PSI-H is one of the three PSI subunits found only in eukaryotes. The
function of PSI-H was characterized in Arabidopsis plants transformed with a psaH
cDNA in sense orientation. Cosuppressed plants containing less than 3% PSI-H are
smaller than wild type when grown on sterile media but are similar to wild type
under optimal conditions. PSI complexes lacking PSI-H contain 50% PSI-L, whereas
other PSI subunits accumulate in wild type amounts. PSI devoid of PSI-H has only
61% NADP+ photoreduction activity compared with wild type and is highly unstable
in the presence of urea as determined from flash-induced absorbance changes at
834 nm. Our data show that PSI-H is required for stable accumulation of PSI and
efficient electron transfer in the complex. The plants lacking PSI-H compensate
for the less efficient PSI with a 15% increase in the P700/chlorophyll ratio, and
this compensation is sufficient to prevent overreduction of the plastoquinone
pool as evidenced by normal photochemical quenching of fluorescence.
Nonphotochemical quenching is approximately 60% of the wild type value,
suggesting that the proton gradient across the thylakoid membrane is decreased in
the absence of PSI-H.
PMID- 10196153
TI - "Half of the sites" binding of D-glyceraldehyde-3-phosphate dehydrogenase folding
intermediate with GroEL.
AB - Two D-glyceraldehyde-3-phosphate dehydrogenase (GAPDH) folding intermediate
subunits bind with chaperonin 60 (GroEL) to form a stable complex, which can no
longer bind with additional GAPDH intermediate subunits, but does bind with one
more lysozyme folding intermediate or one chaperonin 10 (GroES) molecule,
suggesting that the two GAPDH subunits bind at one end of the GroEL molecule
displaying a "half of the sites" binding profile. For lysozyme, GroEL binds with
either one or two folding intermediates to form a stable 1:1 or 1:2 complex with
one substrate on each end of the GroEL double ring for the latter. The 1:1
complex of GroEL.GroES binds with one lysozyme or one dimeric GAPDH folding
intermediate to form a stable ternary complex. Both complexes of GroEL.lysozyme1
and GroEL.GAPDH2 bind with one GroES molecule only at the other end of the GroEL
molecule forming a trans ternary complex. According to the stoichiometry of GroEL
binding with the GAPDH folding intermediate and the formation of ternary
complexes containing GroEL.GAPDH2, it is suggested that the folding intermediate
of GAPDH binds, very likely in the dimeric form, with GroEL at one end only.
PMID- 10196154
TI - A new cytochrome subunit bound to the photosynthetic reaction center in the
purple bacterium, Rhodovulum sulfidophilum.
AB - The nucleotide sequence of the puf operon, which contains the genes encoding the
B870 light-harvesting protein and the reaction center complex of the purple
photosynthetic bacterium, Rhodovulum sulfidophilum, was determined. The operon,
which consisted of six genes, pufQ, pufB, pufA, pufL, pufM, and pufC, is a new
variety in photosynthetic bacteria in the sense that pufQ and pufC coexist. The
amino acid sequence of the cytochrome subunit of the reaction center deduced from
the pufC sequence revealed that this cytochrome contains only three possible heme
binding motifs; the heme-1-binding motif of the corresponding tetraheme
cytochrome subunits was not present. This is the first exception of the
"tetraheme" cytochrome family in purple bacteria and green filamentous bacteria.
The pufC sequence also revealed that the sixth axial ligands to heme-1 and heme-2
irons were not present in the cytochrome either. This cytochrome was actually
detected in membrane preparation as a 43-kDa protein and shown to associate
functionally with the photosynthetic reaction center as the immediate electron
donor to the photo-oxidized special pair of bacteriochlorophyll. This new
cytochrome should be useful for studies on the role of each heme in the
cytochrome subunit of the bacterial reaction center and the evolution of proteins
in photosynthetic electron transfer systems.
PMID- 10196155
TI - Direct EPR detection of the carbonate radical anion produced from peroxynitrite
and carbon dioxide.
AB - The biological effects of peroxynitrite have been recently considered to be
largely dependent on its reaction with carbon dioxide, which is present in high
concentrations in intra- and extracellular compartments. Peroxynitrite anion
(ONOO-) reacts rapidly with carbon dioxide, forming an adduct,
nitrosoperoxocarboxylate (ONOOCO2-), whose decomposition has been proposed to
produce reactive intermediates such as the carbonate radical (CO-3). Here, by the
use of rapid mixing continuous flow electron paramagnetic resonance (EPR), we
directly detected the carbonate radical in flow mixtures of peroxynitrite with
bicarbonate-carbon dioxide over the pH range of 6-9. The radical was
unambiguously identified by its EPR parameters (g = 2.0113; line width = 5.5 G)
and by experiments with bicarbonate labeled with 13C. In this case, the singlet
EPR signal obtained with 12C bicarbonate splits into the expected doublet because
of 13C (a(13C)= 11.7 G). The singlet spectrum of the unlabeled radical was
invariant between pH 6 and 9, confirming that in this pH range the detected
radical is the carbonate radical anion (CO-3). Importantly, in addition to
contributing to the understanding of nitrosoperoxocarboxylate decomposition
pathways, this is the first report unambiguously demonstrating the formation of
the carbonate radical anion at physiological pHs by direct EPR spectroscopy.
PMID- 10196156
TI - Selective stimulation of hepatitis C virus and pestivirus NS5B RNA polymerase
activity by GTP.
AB - NS5B of the hepatitis C virus is an RNA template-dependent RNA polymerase and
therefore the key player of the viral replicase complex. Using a highly purified
enzyme expressed with recombinant baculoviruses in insect cells, we demonstrate a
stimulation of RNA synthesis up to 2 orders of magnitude by high concentrations
of GTP but not with ATP, CTP, UTP, GDP, or GMP. Enhancement of RNA synthesis was
found with various heteropolymeric RNA templates, with poly(C)-oligo(G)12 but not
with poly(A)-oligo(U)12. Several amino acid substitutions in polymerase motifs B,
C, and D previously shown to be crucial for RdRp activity were tested for GTP
stimulation of RNA synthesis. Most of these mutations, in particular those
affecting the GDD motif (motif C) strongly reduced or completely abolished
activation by GTP, suggesting that the same NTP-binding site is used for
stimulation and RNA synthesis. Since GTP did not affect the overall RNA binding
properties or the elongation rate, high concentrations of GTP appear to
accelerate a rate-limiting step at the level of initiation of RNA synthesis.
Finally, enhancement of RNA synthesis by high GTP concentrations was also found
with NS5B of the pestivirus classical swine fever virus, but not with the 3D
polymerase of poliovirus. Thus, stimulation of RdRp activity by GTP is
evolutionarily conserved between the closely related hepaciviruses and
pestiviruses but not between these and the more distantly related picornaviruses.
PMID- 10196157
TI - Glypican-1 is a VEGF165 binding proteoglycan that acts as an extracellular
chaperone for VEGF165.
AB - Glypican-1 is a member of a family of glycosylphosphatidylinositol anchored cell
surface heparan sulfate proteoglycans implicated in the control of cellular
growth and differentiation. The 165-amino acid form of vascular endothelial
growth factor (VEGF165) is a mitogen for endothelial cells and a potent
angiogenic factor in vivo. Heparin binds to VEGF165 and enhances its binding to
VEGF receptors. However, native HSPGs that bind VEGF165 and modulate its receptor
binding have not been identified. Among the glypicans, glypican-1 is the only
member that is expressed in the vascular system. We have therefore examined
whether glypican-1 can interact with VEGF165. Glypican-1 from rat myoblasts binds
specifically to VEGF165 but not to VEGF121. The binding has an apparent
dissociation constant of 3 x 10(-10) M. The binding of glypican-1 to VEGF165 is
mediated by the heparan sulfate chains of glypican-1, because heparinase
treatment abolishes this interaction. Only an excess of heparin or heparan
sulfates but not other types of glycosaminoglycans inhibited this interaction.
VEGF165 interacts specifically not only with rat myoblast glypican-1 but also
with human endothelial cell-derived glypican-1. The binding of 125I-VEGF165 to
heparinase-treated human vascular endothelial cells is reduced following
heparinase treatment, and addition of glypican-1 restores the binding. Glypican-1
also potentiates the binding of 125I-VEGF165 to a soluble extracellular domain of
the VEGF receptor KDR/flk-1. Furthermore, we show that glypican-1 acts as an
extracellular chaperone that can restore the receptor binding ability of VEGF165,
which has been damaged by oxidation. Taken together, these results suggest that
glypican-1 may play an important role in the control of angiogenesis by
regulating the activity of VEGF165, a regulation that may be critical under
conditions such as wound repair, in which oxidizing agents that can impair the
activity of VEGF are produced, and in situations were the concentrations of
active VEGF are limiting.
PMID- 10196158
TI - Mapping functional domains of the guanylate cyclase regulator protein, GCAP-2.
AB - Guanylate cyclase regulator protein (GCAP)-2 is a Ca2+-binding protein that
regulates photoreceptor outer segment membrane guanylate cyclase (RetGC) in a
Ca2+-sensitive manner. GCAP-2 activates RetGC at free Ca2+ concentrations below
100 nM, characteristic of light-adapted photoreceptors, and inhibits RetGC when
free Ca2+ concentrations are above the 500 nM level, characteristic of dark
adapted photoreceptors. We have mapped functional domains in GCAP-2 by using
deletion mutants and chimeric proteins in which parts of GCAP-2 were substituted
with corresponding fragments of other closely related recoverin-like proteins
that do not regulate RetGC. We find that in addition to the EF-hand Ca2+-binding
centers there are three regions that contain GCAP-2-specific sequences essential
for regulation of RetGC. 1) The region between Phe78 and Asp113 determines
whether GCAP-2 activates outer segment RetGC in low or high Ca2+ concentrations.
Substitution of this domain with the corresponding region from neurocalcin causes
a paradoxical behavior of the chimeric proteins. They activate RetGC only at high
and not at low Ca2+ concentrations. 2) The amino acid sequence of GCAP-2 between
Lys29 and Phe48 that includes the EF-hand-related motif EF-1 is essential both
for activation of RetGC at low Ca2+ and inhibition at high Ca2+ concentrations.
Most of the remaining N-terminal region can be substituted with recoverin or
neurocalcin sequences without loss of GCAP-2 function. 3) Region Val171-Asn189,
adjacent to the C-terminal EF-4 contributes to activation of RetGC, but it is not
essential for the ability of Ca2+-loaded GCAP-2 to inhibit RetGC. Other regions
of the molecule can be substituted with the corresponding fragments from
neurocalcin or recoverin, or even partially deleted without preventing GCAP-2
from regulating RetGC. Substitution of these three domains in GCAP-2 with
corresponding neurocalcin sequences also affects activation of individual
recombinant RetGC-1 and RetGC-2 expressed in HEK293 cells.
PMID- 10196159
TI - Mapping sites in guanylyl cyclase activating protein-1 required for regulation of
photoreceptor membrane guanylyl cyclases.
AB - Guanylyl cyclase activating protein (GCAP)-1 regulates photoreceptor membrane
guanylyl cyclase, RetGC, in a Ca2+-sensitive manner. It contains four Ca2+
binding motifs, EF-hands, three of which are capable of binding Ca2+. GCAP-1
activates RetGC in low Ca2+ and inhibits it in high Ca2+. In this study we used
deletion and substitution analysis to identify regions of GCAP-1 sequence that
are specifically required for inhibition and activation. A COOH-terminal sequence
within Met157 to Arg182 is required for activation but not for inhibition of
RetGC. We localized one essential stretch to 5 residues from Arg178 to Arg182.
Another sequence essential for activation is within the N-terminal residues Trp21
to Thr27. The region between EF-hands 1 and 3 of GCAP-1 also contains elements
needed for activation of RetGC. Finally, we found that inhibition of RetGC
requires the first 9 amino-terminal residues of GCAP-1, but none of the residues
from Gln33 to the COOH-terminal Gly205 are specifically required for inhibition.
The ability of GCAP-1 mutants to regulate RetGC was tested on total guanylyl
cyclase activity present in rod outer segments. In addition, the key mutants were
also shown to produce similar effects on recombinant bovine outer segment
cyclases GC1 and GC2.
PMID- 10196160
TI - Transcription activation by CooA, the CO-sensing factor from Rhodospirillum
rubrum. The interaction between CooA and the C-terminal domain of the alpha
subunit of RNA polymerase.
AB - CooA, a member of the cAMP receptor protein (CRP) family, is a CO-sensing
transcription activator from Rhodospirillum rubrum that binds specific DNA
sequences in response to CO. The location of the CooA-binding sites relative to
the start sites of transcription suggested that the CooA-dependent promoters are
analogous to class II CRP-dependent promoters. In this study, we developed an in
vivo CooA reporter system in Escherichia coli and an in vitro transcription assay
using RNA polymerases (RNAP) from E. coli and from Rhodobacter sphaeroides to
study the transcription properties of CooA and the protein-protein interaction
between CooA and RNAP. The ability of CooA to activate CO-dependent transcription
in vivo in heterologous backgrounds suggested that CooA is sufficient to direct
RNAP to initiate transcription and that no other factors are required. This
hypothesis was confirmed in vitro with purified CooA and purified RNAP. Use of a
mutant form of E. coli RNAP with alpha subunits lacking their C-terminal domain
(alpha-CTD) dramatically decreased CooA-dependent transcription of the CooA
regulated R. rubrum promoter PcooF in vitro, which indicates that alpha-CTD plays
an important role in this activation. DNase I footprinting analysis showed that
CooA facilitates binding of wild-type RNAP, but not alpha-CTD-truncated RNAP, to
PcooF. This facilitated binding provides evidence for a direct contact between
CooA and alpha-CTD of RNAP during activation of transcription. Mapping the CooA
contact site in alpha-CTD suggests that CooA is similar but not identical to CRP
in terms of its contact sites to the alpha-CTD at class II promoters.
PMID- 10196161
TI - Human tissue inhibitor of metalloproteinases 3 interacts with both the N- and C
terminal domains of gelatinases A and B. Regulation by polyanions.
AB - We compared the association constants of tissue inhibitor of metalloproteinases
(TIMP)-3 with various matrix metalloproteinases with those for TIMP-1 and TIMP-2
using a continuous assay. TIMP-3 behaved more like TIMP-2 than TIMP-1, showing
rapid association with gelatinases A and B. Experiments with the N-terminal
domain of gelatinase A, the isolated C-terminal domain, or an inactive
progelatinase A mutant showed that the hemopexin domain of gelatinase A makes an
important contribution to the interaction with TIMP-3. The exchange of portions
of the gelatinase A hemopexin domain with that of stromelysin revealed that
residues 568-631 of gelatinase A were required for rapid association with TIMP-3.
The N-terminal domain of gelatinase B alone also showed slower association with
TIMP-3, again implying significant C-domain interactions. The isolation of
complexes between TIMP-3 and progelatinases A and B on gelatin-agarose
demonstrated that TIMP-3 binds to both proenzymes. We analyzed the effect of
various polyanions on the inhibitory activity of TIMP-3 in our soluble assay. The
association rate was increased by dextran sulfate, heparin, and heparan sulfate,
but not by dermatan sulfate or hyaluronic acid. Because TIMP-3 is sequestered in
the extracellular matrix, the presence of certain heparan sulfate proteoglycans
could enhance its inhibitory capacity.
PMID- 10196162
TI - Unconjugated bilirubin exhibits spontaneous diffusion through model lipid
bilayers and native hepatocyte membranes.
AB - The liver is responsible for the clearance and metabolism of unconjugated
bilirubin, the hydrophobic end-product of heme catabolism. Although several
putative bilirubin transporters have been described, it has been alternatively
proposed that bilirubin enters the hepatocyte by passive diffusion through the
plasma membrane. In order to elucidate the mechanism of bilirubin uptake, we
measured the rate of bilirubin transmembrane diffusion (flip-flop) using stopped
flow fluorescence techniques. Unconjugated bilirubin rapidly diffuses through
model phosphatidylcholine vesicles, with a first-order rate constant of 5.3 s-1
(t(1)/(2) = 130 ms). The flip-flop rate is independent of membrane cholesterol
content, phospholipid acyl saturation, and lipid packing, consistent with
thermodynamic analyses demonstrating minimal steric constraint to bilirubin
transmembrane diffusion. The coincident decrease in pH of the entrapped vesicle
volume supports a mechanism whereby the bilirubin molecule crosses the lipid
bilayer as the uncharged diacid. Transport of bilirubin by native rat hepatocyte
membranes exhibits kinetics comparable with that in model vesicles, suggesting
that unconjugated bilirubin crosses cellular membranes by passive diffusion
through the hydrophobic lipid core. In contrast, there is no demonstrable flip
flop of bilirubin diglucuronide or bilirubin ditaurate in phospholipid vesicles,
yet these compounds rapidly traverse isolated rat hepatocyte membranes,
confirming the presence of a facilitated uptake system(s) for hydrophilic
bilirubin conjugates.
PMID- 10196163
TI - Formation of reactive cyclopentenone compounds in vivo as products of the
isoprostane pathway.
AB - Cyclopentenone prostaglandins A2 and J2 are reactive compounds that possess
unique biological activities. However, the extent to which they are formed in
vivo remains unclear. In this study, we explored whether D2/E2-isoprostanes
undergo dehydration in vivo to form A2/J2-isoprostanes. Oxidation of arachidonic
acid in vitro generated a series of compounds that were confirmed to be A2/J2
isoprostanes by mass spectrometric analyses. A2/J2-isoprostanes were detected in
vivo esterified to lipids in livers from normal rats at a level of 5. 1 +/- 2.3
ng/g, and levels increased dramatically by a mean of 24-fold following
administration of CCl4. An A2-isoprostane, 15-A2t-isoprostane, was obtained and
found to readily undergo Michael addition with glutathione and to adduct
covalently to protein. A2/J2-isoprostanes could not be detected in the
circulation, even following CCl4 administration, which we hypothesized might be
explained by rapid formation of adducts. This was supported by finding that
essentially all the radioactivity excreted into the urine following infusion of
radiolabeled 15-A2t-isoprostane into a human volunteer was in the form of a polar
conjugate(s). These data identify a new class of reactive compounds that are
produced in vivo as products of the isoprostane pathway that can exert biological
effects relevant to the pathobiology of oxidant injury.
PMID- 10196164
TI - Miniglucagon (glucagon 19-29), a potent and efficient inhibitor of secretagogue
induced insulin release through a Ca2+ pathway.
AB - Using the MIN6 B-cell line, we investigated the hypothesis that miniglucagon, the
C-terminal () fragment processed from glucagon and present in pancreatic A cells,
modulates insulin release, and we analyzed its cellular mode of action. We show
that, at concentrations ranging from 0.01 to 1000 pM, miniglucagon dose
dependently (ID50 = 1 pM) inhibited by 80-100% the insulin release triggered by
glucose, glucagon, glucagon-like peptide-1-(7-36) amide (tGLP-1), or
glibenclamide, but not that induced by carbachol. Miniglucagon had no significant
effects on cellular cAMP levels. The increase in 45Ca2+ uptake induced by
depolarizing agents (glucose or extracellular K+), by glucagon, or by the
Ca2+channel agonist Bay K-8644 was blocked by miniglucagon at the doses active on
insulin release. Electrophysiological experiments indicated that miniglucagon
induces membrane hyperpolarization, probably by opening potassium channels, which
terminated glucose-induced electrical activity. Pretreatment with pertussis toxin
abolished the effects of miniglucagon on insulin release. It is concluded that
miniglucagon is a highly potent and efficient inhibitor of insulin release by
closing, via hyperpolarization, voltage-dependent Ca2+ channels linked to a
pathway involving a pertussis toxin-sensitive G protein.
PMID- 10196165
TI - Intracellular pH and multidrug resistance regulate complement-mediated
cytotoxicity of nucleated human cells.
AB - In previous work (Weisburg, J. H., Curcio, M., Caron, P. C., Raghi, G.,
Mechetner, E. B., Roepe, P. D., and Scheinberg, D. A. (1996) J. Exp. Med. 183,
2699-2704), we showed that multidrug resistance (MDR) cells created by continuous
selection with the vinca alkaloid vincristine (HL60 RV+) or by retroviral
infection (K562/human MDR 1 cells) exhibited significant resistance to complement
mediated cytotoxicity (CMC). This resistance was due to the presence of
overexpressed P-glycoprotein (P-GP). In this paper, we probe the molecular
mechanism of this phenomenon. We test whether the significant elevated
intracellular pH (pHi) that accompanies P-GP overexpression is sufficient to
confer resistance to CMC and whether this resistance is related to effects on
complement function in the cell membrane. Control HL60 cells not expressing P-GP,
but comparably elevated in cytosolic pHi by two independent methods (CO2
"conditioning" or isotonic Cl- substitution), are tested for CMC using two
different antibody-antigen systems (human IgG and murine IgM; protein and
carbohydrate) and two complement sources (rabbit and human). Elevation of pHi by
either of these methods or by expression of P-GP confers resistance to CMC.
Resistance is not observed when the alkalinization mediated by reverse Cl-/HCO3-
exchange upon Cl- substitution is blocked by treatment with dihydro-4,4'
diisothiocyanostilbene-2,2'-disulfonate. Continuous photometric monitoring of
2',7'-bis(carboxyethyl)-5, 6-carboxyfluorescein (BCECF), to assess changes in pHi
or efflux of the probe through MAC pores, in single cells or cell populations,
respectively, verifies changes in pHi upon CO2 conditioning and Cl- substitution
and release of BCECF upon formation of MAC pores. Antibody binding and
internalization kinetics are similar in both the parental and resistant cell
lines as measured by radioimmunoassay, but flow cytometric data showed that net
complement deposition in the cell membrane is both delayed and reduced in
magnitude in the MDR cells and in the cells with increased pHi. This
interpretation is supported by comparison of BCECF release data for the different
cells. Dual isotopic labeling of key complement components shows no significant
change in molecular stoichiometry of the MACs formed at different pHi. The
results are relevant to understanding clinical implications of MDR, the
physiology of P-GP, and the biochemistry of the complement cascade and further
suggest that the "drug pump" model of P-GP action cannot account for all of its
effects.
PMID- 10196166
TI - The AcbC protein from Actinoplanes species is a C7-cyclitol synthase related to 3
dehydroquinate synthases and is involved in the biosynthesis of the alpha
glucosidase inhibitor acarbose.
AB - The putative biosynthetic gene cluster for the alpha-glucosidase inhibitor
acarbose was identified in the producer Actinoplanes sp. 50/110 by cloning a DNA
segment containing the conserved gene for dTDP-D-glucose 4,6-dehydratase, acbB.
The two flanking genes were acbA (dTDP-D-glucose synthase) and acbC, encoding a
protein with significant similarity to 3-dehydroquinate synthases (AroB
proteins). The acbC gene was overexpressed heterologously in Streptomyces
lividans 66, and the product was shown to be a C7-cyclitol synthase using sedo
heptulose 7-phosphate, but not ido-heptulose 7-phosphate, as its substrate. The
cyclization product, 2-epi-5-epi-valiolone ((2S,3S,4S,5R)-5
(hydroxymethyl)cyclohexanon-2,3,4,5-tetrol), is a precursor of the valienamine
moiety of acarbose. A possible five-step reaction mechanism is proposed for the
cyclization reaction catalyzed by AcbC based on the recent analysis of the three
dimensional structure of a eukaryotic 3-dehydroquinate synthase domain
(Carpenter, E. P., Hawkins, A. R., Frost, J. W., and Brown, K. A. (1998) Nature
394, 299-302).
PMID- 10196167
TI - Bone morphogenetic protein 2 inhibits platelet-derived growth factor-induced c
fos gene transcription and DNA synthesis in mesangial cells. Involvement of
mitogen-activated protein kinase.
AB - Bone morphogenetic proteins (BMPs) play an important role in nephrogenesis. The
biologic effect and mechanism of action of these proteins in the adult kidney has
not yet been studied. We investigated the effect of BMP2, a member of these
growth and differentiation factors, on mitogenic signal transduction pathways
induced by platelet-derived growth factor (PDGF) in glomerular mesangial cells.
PDGF is a growth and survival factor for these cells in vitro and in vivo.
Incubation of mesangial cells with increasing concentrations of BMP2 inhibited
PDGF-induced DNA synthesis in a dose-dependent manner with maximum inhibition at
250 ng/ml. Immune complex tyrosine kinase assay of PDGF receptor beta
immunoprecipitates from lysates of mesangial cells treated with PDGF showed no
inhibitory effect of BMP2 on PDGF receptor tyrosine phosphorylation. This
indicates that the inhibition of DNA synthesis is likely due to postreceptor
events. However, BMP2 significantly inhibited PDGF-stimulated mitogen-activated
protein kinase (MAPK) activity that phosphorylates the Elk-1 transcription
factor, a component of the ternary complex factor. Using a fusion protein-based
reporter assay, we also show that BMP2 blocks PDGF-induced Elk-1-mediated
transcription. Furthermore, we demonstrate that BMP2 inhibits PDGF-induced
transcription of c-fos gene, a natural target of Elk-1 that normally forms a
ternary complex that activates the serum response element of the c-fos gene.
These data provide the first evidence that in mesangial cells, BMP2 signaling
cross-talks with MAPK-based transcriptional events to inhibit PDGF-induced DNA
synthesis. One target for this inhibition is the early response gene c-fos.
PMID- 10196168
TI - A modification of apolipoprotein B accounts for most of the induction of
macrophage growth by oxidized low density lipoprotein.
AB - It has recently been shown that macrophage proliferation occurs during the
progression of atherosclerotic lesions and that oxidized low density lipoprotein
(LDL) stimulates macrophage growth. Possible mechanisms for this include the
interaction of oxidized LDL with integral plasma membrane proteins coupled to
signaling pathways, the release of growth factors and autocrine activation of
growth factor receptors, or the potentiation of mitogenic signal transduction by
a component of oxidized LDL after internalization. The present study was
undertaken to further elucidate the mechanisms involved in the growth-stimulating
effect of oxidized LDL in macrophages. Only extensively oxidized LDL caused
significant growth stimulation, whereas mildly oxidized LDL, native LDL, and
acetyl LDL were ineffective. LDL that had been methylated before oxidation (to
block lysine derivatization by oxidation products and thereby prevent the
formation of a scavenger receptor ligand) did not promote growth, even though
extensive lipid peroxidation had occurred. The growth stimulation could not be
attributed to lysophosphatidylcholine (lyso-PC) because incubation of oxidized
LDL with fatty acid-free bovine serum albumin resulted in a 97% decrease in lyso
PC content but only a 20% decrease in mitogenic activity. Similarly, treatment of
acetyl LDL with phospholipase A2 converted more than 90% of the initial content
of phosphatidylcholine (PC) to lyso-PC, but the phospholipase A2-treated acetyl
LDL was nearly 10-fold less potent than oxidized LDL at stimulating growth.
Platelet-activating factor receptor antagonists partly inhibited growth
stimulation by oxidized LDL, but platelet-activating factor itself did not induce
growth. Digestion of oxidized LDL with phospholipase A2 resulted in the
hydrolysis of PC and oxidized PC but did not attenuate growth induction. Native
LDL, treated with autoxidized arachidonic acid under conditions that caused
extensive modification of lysine residues by lipid peroxidation products but did
not result in oxidation of LDL lipids, was equal to oxidized LDL in potency at
stimulating macrophage growth. Albumin modified by arachidonic acid peroxidation
products also stimulated growth, demonstrating that LDL lipids are not essential
for this effect. These findings suggest that oxidatively modified apolipoprotein
B is the main growth-stimulating component of oxidized LDL, but that oxidized
phospholipids may play a secondary role.
PMID- 10196169
TI - Inhibition of cyclooxygenase-2 gene expression by p53.
AB - Oncogenes enhance the expression of cyclooxygenase (Cox)-2, but interactions
between tumor suppressor genes and Cox-2 have not been studied. In the present
work, we have compared the levels of Cox-2 and the production of prostaglandin E2
in mouse embryo fibroblasts that do not express any p53 ((10)1) versus the same
cell line ((10. 1)Val5) engineered to overexpress wild-type (wt) p53 at 32
degrees C or mutant p53 at 39 degrees C. Cells expressing wt p53 showed about a
10-fold decrease in synthesis of prostaglandin E2 compared with those expressing
mutant p53. Levels of Cox-2 protein and mRNA were markedly suppressed by wt p53
but not by mutant p53. Nuclear run-offs revealed decreased rates of Cox-2
transcription in cells expressing wt p53. The activity of the Cox-2 promoter was
reduced by 85% in cells expressing wt p53 but was reduced only by 30% in cells
expressing mutant p53 compared with cells null for p53. The effect of p53 on the
suppression of Cox-2 promoter activity was localized to the first 40 base pairs
5' from the transcription start site. Electrophoretic mobility shift assay
revealed that p53 competed with TATA-binding protein for binding to mouse Cox-2
or human Cox-2 promoter extending from -50 to +52 base pairs. The results of this
study suggest that interactions between p53 and Cox-2 could be important for
understanding why levels of Cox-2 are undetectable in normal cells and increased
in many tumors.
PMID- 10196170
TI - Differential involvement of MEK kinase 1 (MEKK1) in the induction of apoptosis in
response to microtubule-targeted drugs versus DNA damaging agents.
AB - MEK kinase 1 (MEKK1) is a 196-kDa enzyme that is involved in the regulation of
the c-Jun N-terminal kinase (JNK) pathway and apoptosis. In cells exposed to
genotoxic agents including etoposide and cytosine arabinoside, MEKK1 is cleaved
at Asp874 by caspases. The cleaved kinase domain of MEKK1, itself, stimulates
caspase activity leading to apoptosis. Kinase-inactive MEKK1 expressed in HEK293
cells effectively blocks genotoxin-induced apoptosis. Treatment of cells with
taxol, a microtubule stabilizing agent, did not induce MEKK1 cleavage in cells,
and kinase-inactive MEKK1 expression failed to block taxol-induced apoptosis.
MEKK1 became activated in HEK293 cells exposed to taxol, but in contrast to
etoposide-treatment, taxol failed to increase JNK activity. Taxol treatment of
cells, therefore, dissociates MEKK1 activation from the regulation of the JNK
pathway. Overexpression of anti-apoptotic Bcl2 blocked MEKK1 and taxol-induced
apoptosis but did not block the caspase-dependent cleavage of MEKK1 in response
to etoposide. This indicates Bcl2 inhibition of apoptosis is, therefore,
downstream of caspase-dependent MEKK1 cleavage. The results define the
involvement of MEKK1 in the induction of apoptosis by genotoxins but not
microtubule altering drugs.
PMID- 10196171
TI - Transmembrane segment 5 of the Glut1 glucose transporter is an amphipathic helix
that forms part of the sugar permeation pathway.
AB - Transmembrane segment 5 of the Glut1 glucose transporter has been proposed to
form an amphipathic transmembrane helix that lines the substrate translocation
pathway (Mueckler, M., Caruso, C., Baldwin, S. A., Panico, M., Blench, I.,
Morris, H. R., Allard, W. J., Lienhard, G. E., and Lodish, H. F. (1985) Science
229, 941-945). This hypothesis was tested using cysteine-scanning mutagenesis in
conjunction with the membrane-impermeant, sulfhydryl-specific reagent, p
chloromercuribenzenesulfonate (pCMBS). A series of 21 mutants was created from a
fully functional, cysteine-less, parental Glut1 molecule by changing each residue
within putative transmembrane segment 5 to cysteine. Each mutant was then
expressed in Xenopus oocytes and its steady-state protein level, 2-deoxyglucose
uptake activity, and sensitivity to pCMBS were measured. All 21 mutants exhibited
measurable transport activity, although several of the mutants exhibited reduced
activity due to a corresponding reduction in steady-state protein. Six of the
amino acid side chains within transmembrane segment 5 were clearly accessible to
pCMBS in the external medium, as determined by inhibition of transport activity,
and a 7th residue showed inhibition that lacked statistical significance because
of the extremely low transport activity of the corresponding mutant. All 7 of
these residues were clustered along one face of a putative alpha-helix, proximal
to the exoplasmic surface of the plasma membrane. These results comprise the
first experimental evidence for the existence of an amphipathic transmembrane
alpha-helix in a glucose transporter molecule and strongly suggest that
transmembrane segment 5 of Glut1 forms part of the sugar permeation pathway.
PMID- 10196173
TI - Interactions of CcdB with DNA gyrase. Inactivation of Gyra, poisoning of the
gyrase-DNA complex, and the antidote action of CcdA.
AB - The F plasmid-carried bacterial toxin, the CcdB protein, is known to act on DNA
gyrase in two different ways. CcdB poisons the gyrase-DNA complex, blocking the
passage of polymerases and leading to double-strand breakage of the DNA.
Alternatively, in cells that overexpress CcdB, the A subunit of DNA gyrase (GyrA)
has been found as an inactive complex with CcdB. We have reconstituted the
inactive GyrA-CcdB complex by denaturation and renaturation of the purified GyrA
dimer in the presence of CcdB. This inactivating interaction involves the N
terminal domain of GyrA, because similar inactive complexes were formed by
denaturing and renaturing N-terminal fragments of the GyrA protein in the
presence of CcdB. Single amino acid mutations, both in GyrA and in CcdB, that
prevent CcdB-induced DNA cleavage also prevent formation of the inactive
complexes, indicating that some essential interaction sites of GyrA and of CcdB
are common to both the poisoning and the inactivation processes. Whereas the
lethal effect of CcdB is most probably due to poisoning of the gyrase-DNA
complex, the inactivation pathway may prevent cell death through formation of a
toxin-antitoxin-like complex between CcdB and newly translated GyrA subunits.
Both poisoning and inactivation can be prevented and reversed in the presence of
the F plasmid-encoded antidote, the CcdA protein. The products of treating the
inactive GyrA-CcdB complex with CcdA are free GyrA and a CcdB-CcdA complex of
approximately 44 kDa, which may correspond to a (CcdB)2(CcdA)2 heterotetramer.
PMID- 10196172
TI - Cyclic GMP-dependent protein kinase activates cloned BKCa channels expressed in
mammalian cells by direct phosphorylation at serine 1072.
AB - NO-induced activation of cGMP-dependent protein kinase (PKG) increases the open
probability of large conductance Ca2+-activated K+ channels and results in smooth
muscle relaxation. However, the molecular mechanism of channel regulation by the
NO-PKG pathway has not been determined on cloned channels. The present study was
designed to clarify PKG-mediated modulation of channels at the molecular level.
The cDNA encoding the alpha-subunit of the large conductance Ca2+-activated K+
channel, cslo-alpha, was expressed in HEK293 cells. Whole cell and single channel
characteristics of cslo-alpha exhibited functional features of native large
conductance Ca2+-activated K+ channels in smooth muscle cells. The NO-donor
sodium nitroprusside increased outward current 2.3-fold in whole cell recordings.
In cell-attached patches, sodium nitroprusside increased the channel open
probability (NPo) of cslo-alpha channels 3.3-fold without affecting unitary
conductance. The stimulatory effect of sodium nitroprusside was inhibited by the
PKG-inhibitor KT5823. Direct application of PKG-Ialpha to the cytosolic surface
of inside-out patches increased NPo 3.2-fold only in the presence of ATP and cGMP
without affecting unitary conductance. A point mutation of cslo-alpha in which
Ser-1072 (the only optimal consensus sequence for PKG phosphorylation) was
replaced by Ala abolished the PKG effect on NPo in inside-out patches and the
effect of SNP in cell attached patches. These results indicate that PKG activates
cslo-alpha by direct phosphorylation at serine 1072.
PMID- 10196174
TI - Distinct secondary structures of the leucine-rich repeat proteoglycans decorin
and biglycan. Glycosylation-dependent conformational stability.
AB - Biglycan and decorin have been overexpressed in eukaryotic cells and two major
glycoforms isolated under native conditions: a proteoglycan substituted with
glycosaminoglycan chains; and a core protein form secreted devoid of
glycosaminoglycans (Hocking, A. M., Strugnell, R. A., Ramamurthy, P., and
McQuillan, D. J. (1996) J. Biol. Chem. 271, 19571-19577; Ramamurthy, P., Hocking,
A. M., and McQuillan, D. J. (1996) J. Biol. Chem. 271, 19578-19584). Far-UV CD
spectroscopy of decorin and biglycan proteoglycans indicates that, although they
are predominantly beta-sheet, biglycan has a significantly higher content of
alpha-helical structure. Decorin proteoglycan and core protein are very similar,
whereas the biglycan core protein exhibits closer similarity to the decorin
glycoforms than to the biglycan proteoglycan form. However, enzymatic removal of
the chondroitin sulfate chains from biglycan proteoglycan does not induce a shift
to the core protein structure, suggesting that the final form is influenced by
polysaccharide addition only during biosynthesis. Fluorescence emission
spectroscopy demonstrated that the single tryptophan residue, which is at a
conserved position at the C-terminal domain of both biglycan and decorin, is
found in similar microenvironments. This indicates that in this specific domain
the different glycoforms do exhibit apparent conservation of structure. Exposure
of decorin and biglycan to 10 M urea resulted in an increase in fluorescent
intensity, which indicates that the emission from tryptophan in the native state
is quenched. Comparison of urea-induced protein unfolding curves provide further
evidence that decorin and biglycan assume different structures in solution.
Decorin proteoglycan and core protein unfold in a manner similar to a classic two
state model, in which there is a steep transition to an unfolded state between 1
and 2 M urea. The biglycan core protein also shows a similar steep transition.
However, biglycan proteoglycan shows a broad unfolding transition between 1 and 6
M urea, probably indicating the presence of stable unfolding intermediates.
PMID- 10196175
TI - Alternative splicing determines the intracellular localization of the novel
nuclear protein Nop30 and its interaction with the splicing factor SRp30c.
AB - We report on the molecular cloning of a novel human cDNA by its interaction with
the splicing factor SRp30c in a yeast two-hybrid screen. This cDNA is
predominantly expressed in muscle and encodes a protein that is present in the
nucleoplasm and concentrated in nucleoli. It was therefore termed Nop30
(nucleolar protein of 30 kDa). We have also identified a related cDNA with a
different carboxyl terminus. Sequencing of the NOP gene demonstrated that both
cDNAs are generated by alternative 5' splice site usage from a single gene that
consists of four exons, spans at least 1800 nucleotides, and is located on
chromosome 16q21-q23. The alternative 5' splice site usage introduces a
frameshift creating two different carboxyl termini. The carboxyl terminus of
Nop30 is rich in serines and arginines and has been found to target the protein
into the nucleus, whereas its isoform is characterized by proline/glutamic acid
dipeptides in its carboxyl terminus and is predominantly found in the cytosol.
Interaction studies in yeast, in vitro protein interaction assays, and co
immunoprecipitations demonstrated that Nop30 multimerizes and binds to the RS
domain of SRp30c but not to other splicing factors tested. Overexpression of
Nop30 changes alternative exon usage in preprotachykinin and SRp20 reporter
genes, suggesting that Nop30 influences alternative splice site selection in
vivo.
PMID- 10196176
TI - Proliferative defect and embryonic lethality in mice homozygous for a deletion in
the p110alpha subunit of phosphoinositide 3-kinase.
AB - Phosphatidylinositol 3,4,5-trisphosphate is a phospholipid signaling molecule
involved in many cellular functions including growth factor receptor signaling,
cytoskeletal organization, chemotaxis, apoptosis, and protein trafficking.
Phosphorylation at the 3 position of the inositol ring is catalyzed by many
different 3-kinases (classified as types IA, IB, II, and III), but the
physiological roles played by each of the different 3-kinase isozymes during
embryonic development and in homeostasis in animals is incompletely understood.
Mammalian type IA kinase isozymes are heterodimers that are active at 37 degrees
C when the catalytic 110-kDa subunit interacts through an amino-terminal binding
domain with a regulatory 85- or 55-kDa subunit. Using gene targeting in embryonic
stem cells, we deleted this binding domain in the gene encoding the alpha isoform
of the 110-kDa catalytic subunit (Pik3ca) of the alpha isozyme of the type IA
kinases, leading to loss of expression of the p110 catalytic subunit. We show
that Pik3cadel/del embryos are developmentally delayed at embryonic day (E) 9.5
and die between E9.5 and E10.5. E9. 5 Pik3cadel/del embryos have a profound
proliferative defect but no increase in apoptosis. A proliferative defect is
supported by the observation that fibroblasts from Pik3cadel/del embryos fail to
replicate in Dulbecco's modified Eagle's medium and fetal calf serum, even with
supplemental growth factors.
PMID- 10196177
TI - Identification of the individual residues that determine human CD59 species
selective activity.
AB - Formation of the cytolytic membrane attack complex of complement on host cells is
inhibited by the membrane-bound glycoprotein, CD59. The inhibitory activity of
CD59 is species restricted, and human CD59 is not effective against rat
complement. Previous functional analysis of chimeric human/rat CD59 proteins
indicated that the residues responsible for the species selective function of
human CD59 map to a region contained between positions 40 and 66 in the primary
structure. By comparative analysis of rat and human CD59 models and by mutational
analysis of candidate residues, we now identify the individual residues within
the 40-66 region that confer species selective function on human CD59. All
nonconserved residues within the 40-66 sequence were substituted from human to
rat residues in a series of chimeric human/rat CD59 mutant proteins. Functional
analysis revealed that the individual human to rat residue substitutions F47A,
T51L, R55E, and K65Q each produced a mutant human CD59 protein with enhanced rat
complement inhibitory activity with the single F47A substitution having the most
significant effect. Interestingly, the side chains of the residues at positions
47, 51, and 55 are all located on the short single helix (residues 47-55) of CD59
and form an exposed continuous strip parallel to the helix axis. A single human
CD59 mutant protein containing rat residue substitutions at all three helix
residues produced a protein with species selective activity comparable to that of
rat CD59. We further found that synthetic peptides spanning the human CD59 helix
sequence were able to inhibit the binding of human CD59 to human C8, but had
little effect on the binding of rat CD59 to rat C8.
PMID- 10196178
TI - Expression of macrophage MARCO receptor induces formation of dendritic plasma
membrane processes.
AB - MARCO is a novel macrophage-specific receptor structurally related to macrophage
class A scavenger receptors. It is constitutively expressed in macrophages of the
marginal zone of the spleen and in lymph nodes and is up-regulated in other
tissues during systemic bacterial infections. In this study, we show that ectopic
expression of MARCO in cell lines such as Chinese hamster ovary, HeLa, NIH3T3,
and 293 induces dramatic cell shape changes. Typically these changes include
formation of large lamellipodia-like structures and of long dendritic processes.
The morphological changes are accompanied by disassembly of actin stress fibers
and often also by complete loss of focal adhesions. The MARCO-induced changes are
dependent on cell adhesion and are inhibited, but not completely abolished, when
the cells are plated on fibronectin-coated surfaces. Similarly, a dominant
negative mutant of the Rho family GTPase Rac1 partially inhibited the morphogenic
effects of MARCO in Chinese hamster ovary cells, whereas a dominant-negative form
of a related protein, Cdc42, did not. Expression studies with a variety of
truncated MARCO forms indicated that the proximal segment of the cysteine-rich
domain V is important for the morphoregulatory activity. The results indicate
that expression of MARCO has a direct effect in generating the phenotype of
activated macrophages necessary for the trapping and removal of pathogens and
other foreign substances.
PMID- 10196179
TI - Phosphatidylinositol 3-kinase-dependent membrane association of the Bruton's
tyrosine kinase pleckstrin homology domain visualized in single living cells.
AB - Phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) has been proposed to act
as a second messenger to recruit regulatory proteins to the plasma membrane via
their pleckstrin homology (PH) domains. The PH domain of Bruton's tyrosine kinase
(Btk), which is mutated in the human disease X-linked agammaglobulinemia, has
been shown to interact with PI(3,4,5)P3 in vitro. In this study, a fusion protein
containing the PH domain of Btk and the enhanced green fluorescent protein (BtkPH
GFP) was constructed and utilized to study the ability of this PH domain to
interact with membrane inositol phospholipids inside living cells. The
localization of expressed BtkPH-GFP in quiescent NIH 3T3 cells was
indistinguishable from that of GFP alone, both being cytosolic as assessed by
confocal microscopy. In NIH 3T3 cells coexpressing BtkPH-GFP and the epidermal
growth factor receptor, activation of epidermal growth factor or endogenous
platelet-derived growth factor receptors caused a rapid (<3 min) translocation of
the cytosolic fluorescence to ruffle-like membrane structures. This response was
not observed in cells expressing GFP only and was completely inhibited by
treatment with the PI 3-kinase inhibitors wortmannin and LY 292004. Membrane
targeted PI 3-kinase also caused membrane localization of BtkPH-GFP that was
slowly reversed by wortmannin. When the R28C mutation of the Btk PH domain, which
causes X-linked agammaglobulinemia, was introduced into the fluorescent
construct, no translocation was observed after stimulation. In contrast, the E41K
mutation, which confers transforming activity to native Btk, caused significant
membrane localization of BtkPH-GFP with characteristics indicating its possible
binding to PI(4,5)P2. This mutant, but not wild-type BtkPH-GFP, interfered with
agonist-induced PI(4,5)P2 hydrolysis in COS-7 cells. These results show in intact
cells that the PH domain of Btk binds selectively to 3-phosphorylated lipids
after activation of PI 3-kinase enzymes and that losing such binding ability or
specificity results in gross abnormalities in the function of the enzyme.
Therefore, the interaction with PI(3,4,5)P3 is likely to be an important
determinant of the physiological regulation of Btk and can be utilized to
visualize the dynamics and spatiotemporal organization of changes in this
phospholipid in living cells.
PMID- 10196180
TI - Two distinct regions of cyclophilin B are involved in the recognition of a
functional receptor and of glycosaminoglycans on T lymphocytes.
AB - Cyclophilin B is a cyclosporin A-binding protein exhibiting peptidyl-prolyl
cis/trans isomerase activity. We have previously shown that it interacts with two
types of binding sites on T lymphocytes. The type I sites correspond to specific
functional receptors and the type II sites to sulfated glycosaminoglycans. The
interactions of cyclophilin B with type I and type II sites are reduced in the
presence of cyclosporin A and of a synthetic peptide mimicking the N-terminal
part of cyclophilin B, respectively, suggesting that the protein possesses two
distinct binding regions. In this study, we intended to characterize the areas of
cyclophilin B involved in the interactions with binding sites present on Jurkat
cells. The use of cyclophilin B mutants modified in the N-terminal region
demonstrated that the 3Lys-Lys-Lys5 and 14Tyr-Phe-Asp16 clusters are probably
solely required for the interactions with the type II sites. We further
engineered mutants of the conserved central core of cyclophilin B, which bears
the catalytic and the cyclosporin A binding sites as an approach to localize the
binding regions for the type I sites. The enzymatic activity of cyclophilin B was
dramatically reduced after substitution of the Arg62 and Phe67 residues, whereas
the cyclosporin A binding activity was destroyed by mutation of the Trp128
residue and strongly decreased after modification of the Phe67 residue. Only the
substitution of the Trp128 residue reduced the binding of the resulting
cyclophilin B mutant to type I binding sites. The catalytic site of cyclophilin B
therefore did not seem to be essential for cellular binding and the cyclosporin A
binding site appeared to be partially involved in the binding to type I sites.
PMID- 10196181
TI - Cellular trafficking of G protein-coupled receptor/beta-arrestin endocytic
complexes.
AB - beta-Arrestins are multifunctional proteins identified on the basis of their
ability to bind and uncouple G protein-coupled receptors (GPCR) from
heterotrimeric G proteins. In addition, beta-arrestins play a central role in
mediating GPCR endocytosis, a key regulatory step in receptor resensitization. In
this study, we visualize the intracellular trafficking of beta-arrestin2 in
response to activation of several distinct GPCRs including the beta2-adrenergic
receptor (beta2AR), angiotensin II type 1A receptor (AT1AR), dopamine D1A
receptor (D1AR), endothelin type A receptor (ETAR), and neurotensin receptor
(NTR). Our results reveal that in response to beta2AR activation, beta-arrestin2
translocation to the plasma membrane shares the same pharmacological profile as
described for receptor activation and sequestration, consistent with a role for
beta-arrestin as the agonist-driven switch initiating receptor endocytosis.
Whereas redistributed beta-arrestins are confined to the periphery of cells and
do not traffic along with activated beta2AR, D1AR, and ETAR in endocytic
vesicles, activation of AT1AR and NTR triggers a clear time-dependent
redistribution of beta-arrestins to intracellular vesicular compartments where
they colocalize with internalized receptors. Activation of a chimeric AT1AR with
the beta2AR carboxyl-terminal tail results in a beta-arrestin membrane
localization pattern similar to that observed in response to beta2AR activation.
In contrast, the corresponding chimeric beta2AR with the AT1AR carboxyl-terminal
tail gains the ability to translocate beta-arrestin to intracellular vesicles.
These results demonstrate that the cellular trafficking of beta-arrestin proteins
is differentially regulated by the activation of distinct GPCRs. Furthermore,
they suggest that the carboxyl-tail of the receptors might be involved in
determining the stability of receptor/betaarrestin complexes and cellular
distribution of beta-arrestins.
PMID- 10196182
TI - Plastidic pathway of serine biosynthesis. Molecular cloning and expression of 3
phosphoserine phosphatase from Arabidopsis thaliana.
AB - In plants, Ser is biosynthesized by two different pathways: a photorespiratory
pathway via Gly and a plastidic pathway via the phosphorylated metabolites from 3
phosphoglycerate. In contrast to the better characterization of the
photorespiratory pathway at a molecular level, the molecular regulation and
significance of the plastidic pathway are not yet well understood. An Arabidopsis
thaliana cDNA encoding 3-phosphoserine phosphatase, the enzyme that is
responsible for the conversion of 3-phosphoserine to Ser in the final step of the
plastidic pathway of Ser biosynthesis, was cloned by functional complementation
of an Escherichia coli serB- mutant. The 1.1-kilobase pair full-length cDNA,
encoding 295 amino acids in its open reading frame, contains a putative organelle
targeting presequence. Chloroplastic targeting has been demonstrated by particle
gun bombardment using an N-terminal 60-amino acid green fluorescence protein
fusion protein. Southern hybridization suggested the existence of a single-copy
gene that mapped to chromosome 1. 3-Phosphoserine phosphatase enzyme activity was
detected in vitro in the overexpressed protein in E. coli. Northern analysis
revealed preferential gene expression in leaf and root tissues of light-grown
plants with an approximately 1.5-fold abundance in the root compared with the
leaf tissues. This indicates the possible role of the plastidic pathway in
supplying Ser to non-photosynthetic tissues, in contrast to the function of the
photorespiratory pathway in photosynthetic tissues. This work completes the
molecular cloning and characterization of the three genes involved in the
plastidic pathway of Ser biosynthesis in higher plants.
PMID- 10196183
TI - Involucrin cross-linking by transglutaminase 1. Binding to membranes directs
residue specificity.
AB - The transglutaminase 1 (TGase 1) enzyme is essential for the assembly of the cell
envelope barrier in stratified squamous epithelia. It is usually bound to
membranes, but to date most studies with it have involved solution assays. Here
we describe an in vitro model system for characterizing the function of TGase 1
on the surface of synthetic lipid vesicles (SLV) of composition similar to
eukaryote plasma membranes. Recombinant baculovirus-expressed human TGase 1
readily binds to SLV and becomes active in cross-linking above 10 microM Ca2+, in
comparison to above 100 microM in solution assays, suggesting that the membrane
surface is important for enzyme function. Involucrin also binds to SLV containing
12-18% phosphatidylserine and at Ca2+ concentrations above 1 microM. In reactions
of involucrin with TGase 1 enzyme in solution, 80 of its 150 glutamines serve as
donor residues. However, on SLV carrying both involucrin and TGase 1, only five
glutamines serve as donors, of which glutamine 496 was the most favored. As
controls, there was no change in specificity toward the glutamines of other
substrates used by free or SLV-bound TGase 1 enzyme. We propose a model in which
involucrin and TGase 1 bind to membranes shortly after expression in
differentiating keratinocytes, but cross-linking begins only later as
intracellular Ca2+ levels increase. Furthermore, the data suggest that the
membrane surface regulates the steric interaction of TGase 1 with substrates such
as involucrin to permit specific cross-linking for initiation of cell envelope
barrier formation.
PMID- 10196184
TI - Altered regulation of cyclin G in human breast cancer and its specific
localization at replication foci in response to DNA damage in p53+/+ cells.
AB - Cyclin G, a recent addition to the cyclin family, was initially identified in
screens for new src kinase family members and soon thereafter by differential
screening for transcriptional targets of the tumor suppressor gene, p53. We have
identified cyclin G as being overexpressed in breast and prostate cancer cells
using differential display polymerase chain reaction screening. We demonstrate
here that cyclin G is overexpressed in human breast and prostate cancer cells and
in cancer cells in situ from tumor specimens. Cyclin G expression was tightly
regulated throughout the cell cycle in normal breast cells, peaking at the S and
G2/M phases of the cell cycle with lower levels in G1. The cell cycle-dependent
expression was absent in breast cancer cells. Following DNA damage in normal
p53+/+ cells, cyclin G is triggered to cluster in discrete nuclear DNA
replication foci that contain replication-associated proteins such as
proliferating cell nuclear antigen (PCNA). While p53-/- cells displayed a faint
cyclin G nuclear staining pattern, there was no increased expression and no
change in distribution of the staining pattern after DNA damage. The specific
subcellular localization of cyclin G at DNA replication foci provides an
additional link between p53-mediated growth arrest and cell cycle regulation and
suggests that cyclin G may act as an effector of p53-mediated events by
functional association with replication foci protein(s).
PMID- 10196185
TI - Ovalbumin in developing chicken eggs migrates from egg white to embryonic organs
while changing its conformation and thermal stability.
AB - Ovalbumin was detected in developing chicken eggs. The large majority of these
ovalbumin molecules was found to be in a heat-stable form reminiscent of S
ovalbumin. About 83 and 90% of the ovalbumin population was in a heat-stable form
in day 14 or stage 40 amniotic fluid and day 18 or stage 44 egg yolk,
respectively, whereas ovalbumin in newly deposited eggs was in the heat-unstable,
native form. Purified preparations of stable ovalbumin from egg white and
amniotic fluid showed a less ordered configuration than native ovalbumin, as
analyzed by circular dichroism and differential scanning calorimetry. In
addition, mass spectrometric analysis exhibited distinct size microheterogeneity
between the stable and native forms of ovalbumin. Immunohisotochemical study
revealed that ovalbumin was present in the central nervous system and other
embryonic organs. These results indicated that egg white ovalbumin migrates into
the developing embryo while changing its higher order structure.
PMID- 10196186
TI - Sphingolipid activator proteins are required for epidermal permeability barrier
formation.
AB - The epidermal permeability barrier is maintained by extracellular lipid membranes
within the interstices of the stratum corneum. Ceramides, the major components of
these multilayered membranes, derive in large part from hydrolysis of
glucosylceramides mediated by stratum corneum beta-glucocerebrosidase (beta
GlcCerase). Prosaposin (pSAP) is a large precursor protein that is
proteolytically cleaved to form four distinct sphingolipid activator proteins,
which stimulate enzymatic hydrolysis of sphingolipids, including
glucosylceramide. Recently, pSAP has been eliminated in a mouse model using
targeted deletion and homologous recombination. In addition to the extracutaneous
findings noted previously, our present data indicate that pSAP deficiency in the
epidermis has significant consequences including: 1) an accumulation of epidermal
glucosylceramides together with below normal levels of ceramides; 2) alterations
in lipids that are bound by ester linkages to proteins of the cornified cell
envelope; 3) a thickened stratum lucidum with evidence of scaling; and 4) a
striking abnormality in lamellar membrane maturation within the interstices of
the stratum corneum. Together, these results demonstrate that the production of
pSAP, and presumably mature sphingolipid activator protein generation, is
required for normal epidermal barrier formation and function. Moreover, detection
of significant amounts of covalently bound omega-OH-GlcCer in pSAP-deficient
epidermis suggests that deglucosylation to omega-OH-Cer is not a requisite step
prior to covalent attachment of lipid to cornified envelope proteins.
PMID- 10196187
TI - A novel cytotoxin from Clostridium difficile serogroup F is a functional hybrid
between two other large clostridial cytotoxins.
AB - The large clostridial cytotoxins (LCTs) constitute a group of high molecular
weight clostridial cytotoxins that inactivate cellular small GTP-binding
proteins. We demonstrate that a novel LCT (TcdB-1470) from Clostridium difficile
strain 1470 is a functional hybrid between "reference" TcdB-10463 and Clostridium
sordellii TcsL-1522. It bound to the same specific receptor as TcdB-10463 but
glucosylated the same GTP-binding proteins as TcsL-1522. All three toxins had
equal enzymatic potencies but were equally cytotoxic only when microinjected.
When applied extracellularly TcdB-1470 and TcdB-10463 were considerably more
potent cytotoxins than TcsL-1522. The small GTP-binding protein R-Ras was
identified as a target for TcdB-1470 and also for TcsL-1522 but not for TcdB
10463. R-Ras is known to control integrin-extracellular matrix interactions from
inside the cell. Its glucosylation may be a major determinant for the cell
rounding and detachment induced by the two R-Ras-attacking toxins. In contrast,
fibroblasts treated with TcdB-10463 were arborized and remained attached, with
phosphotyrosine containing structures located at the cell-to-cell contacts and
beta3-integrin remaining at the tips of cellular protrusions. These components
were absent from cells treated with the R-Ras-inactivating toxins. The novel
hybrid toxin will broaden the utility of the LCTs for clarifying the functions of
several small GTPases, now including also R-Ras.
PMID- 10196188
TI - An alternative splicing form of phosphatidylserine-specific phospholipase A1 that
exhibits lysophosphatidylserine-specific lysophospholipase activity in humans.
AB - Phosphatidylserine-specific phospholipase A1 (PS-PLA1), which acts specifically
on phosphatidylserine (PS) and 1-acyl-2-lysophosphatidylserine (lyso-PS) to
hydrolyze fatty acids at the sn-1 position of these phospholipids, was first
identified in rat platelets (Sato, T., Aoki, J., Nagai, Y., Dohmae, N., Takio,
K., Doi, T., Arai, H., and Inoue, K. (1997) J. Biol. Chem. 272, 2192-2198). In
this study we isolated and sequenced cDNA clones encoding human PS-PLA1, which
showed 80% homology with rat PS-PLA1 at the amino acid level. In addition to an
mRNA encoding a 456-amino acid product (PS-PLA1), an mRNA with four extra bases
inserted at the boundary of the exon-intron junction was detected in human
tissues and various human cell lines. This mRNA is most probably produced via an
alternative use of the 5'-splicing site (two consensus sequences for RNA splicing
occur at the boundary of the exon-intron junction) and encodes a 376-amino acid
product (PS-PLA1DeltaC) that lacks two-thirds of the C-terminal domain of PS
PLA1. Unlike PS-PLA1, PS-PLA1DeltaC hydrolyzed exclusively lyso-PS but not PS
appreciably. Any other phospholipids such as phosphatidylcholine (PC),
phosphatidylethanolamine (PE), phosphatidic acid (PA), and their lyso derivatives
were not hydrolyzed at all. These data demonstrated that PS-PLA1DeltaC exhibits
lyso-PS-specific lysophospholipase activity and that the C-terminal domain of PS
PLA1 is responsible for recognizing diacylphospholipids. In addition, human PS
PLA1 gene was mapped to chromosome 3q13.13-13.2 and was unexpectedly identical to
the nmd gene, which is highly expressed in nonmetastatic melanoma cell lines but
poorly expressed in metastatic cell lines (van Groningen, J. J., Bloemers, H. P.,
and Swart, G. W. (1995) Cancer Res. 55, 6237-6243).
PMID- 10196189
TI - Human acyl-CoA:cholesterol acyltransferase-1 (ACAT-1) gene organization and
evidence that the 4.3-kilobase ACAT-1 mRNA is produced from two different
chromosomes.
AB - Acyl-CoA:cholesterol acyltransferase (ACAT) plays important roles in cellular
cholesterol homeostasis. Four human ACAT-1 mRNAs (7.0, 4.3, 3.6, and 2.8
kilobases (kb)) share the same short 5'-untranslated region (exon 1) and coding
sequence (exons 2-15). The 4.3-kb mRNA contains an additional 5'-untranslated
region (1289 nucleotides in length; exons Xa and Xb) immediately upstream from
the exon 1 sequence. One ACAT-1 genomic DNA insert covers exons 1-16 and a
promoter (the P1 promoter). A separate insert covers exon Xa (1277 base pairs)
and a different promoter (the P7 promoter). Gene mapping shows that exons 1-16
and the P1 promoter sequences are located in chromosome 1, while exon Xa and the
P7 promoter sequence are located in chromosome 7. RNase protection assays
demonstrate three different protected fragments, corresponding to the 4.3-kb mRNA
and the two other mRNAs transcribed from the two promoters. These results are
consistent with the interpretation that the 4.3-kb mRNA is produced from two
different chromosomes, by a novel RNA recombination mechanism involving trans
splicing of two discontinuous precursor RNAs.
PMID- 10196190
TI - Metastability in the inhibitory mechanism of human alpha1-antitrypsin.
AB - Metastability of the native form of proteins has been recognized as a mechanism
of biological regulation. The energy-loaded structure of the fusion protein of
influenza virus and the strained native structure of serpins (serine protease
inhibitors) are typical examples. To understand the structural basis and
functional role of the native metastability of inhibitory serpins, we
characterized stabilizing mutations of alpha1-antitrypsin in a region presumably
involved in complex formation with a target protease. We found various
unfavorable interactions such as overpacking of side chains, polar-nonpolar
interactions, and cavities as the structural basis of the native metastability.
For several stabilizing mutations, there was a concomitant decrease in the
inhibitory activity. Remarkably, some substitutions at Lys-335 increased the
stability over 6 kcal mol-1 with simultaneous loss of activity over 30% toward
porcine pancreatic elastase. Considering the location and energetic cost of Lys
335, we propose that this lysine plays a pivotal role in conformational switch
during complex formation. Our current results are quite contradictory to those of
previously reported hydrophobic core mutations, which increased the stability up
to 9 kcal mol-1 without any significant loss of activity. It appears that the
local strain of inhibitory serpins is critical for the inhibitory activity.
PMID- 10196191
TI - Discriminatory residues in Ras and Rap for guanine nucleotide exchange factor
recognition.
AB - The inability of the S17N mutant of Rap1A to sequester the catalytic domain of
the Rap guanine nucleotide exchange factor C3G (van den Berghe, N., Cool, R. H.,
Horn, G., and Wittinghofer, A. (1997) Oncogene 15, 845-850) prompted us to study
possible fundamental differences in the way Rap1 interacts with C3G compared with
the interaction of Ras with the catalytic domain of the mouse Ras guanine
nucleotide exchange factor Cdc25(Mm). A variety of mutants in both Ras and Rap1A
were designed, and both the C3G and Cdc25(Mm) catalyzed release of guanine
nucleotide from these mutants was studied. In addition, we could identify regions
in Rap2A that are responsible for the lack of recognition by C3G and induce high
C3G activity by replacement of these residues with the corresponding Rap1A
residues. The different Ras and Rap mutants showed that many residues were
equally important for both C3G and Cdc25(Mm), suggesting that they interact
similarly with their substrates. However, several residues were also identified
to be important for the exchange reaction with only C3G (Leu70) or only Cdc25(Mm)
(Gln61 and Tyr40). These results are discussed in the light of the structure of
the Ras-Sos complex and suggest that some important differences in the
interaction of Rap1 with C3G and Ras with Cdc25(Mm) indeed exist and that marker
residues have been identified for the different structural requirements.
PMID- 10196192
TI - Complete mapping of divergent amino acids responsible for differential ligand
binding of folate receptors alpha and beta.
AB - The folate receptor (FR) type alpha may be distinguished from FR-beta by its
higher affinity for the circulating folate coenzyme, (6S)-5
methyltetrahydrofolate (5-CH3H4folate), and its opposite stereospecificity for
reduced folate coenzymes. Previous studies showed that a single leucine to
alanine substitution at position 49 of the mature protein sequence is responsible
for the functional divergence of FR-beta (Shen, F., Zheng, X., Wang, H., and
Ratnam, M. (1997) Biochemistry 36, 6157-6163); however, the results also
indicated that the minimum requirement for conversion of FR-beta to the
functional equivalent of FR-alpha should include amino acid substitution(s)
downstream of residue 92 in addition to mutation of L49A. To pinpoint those
residues, chimeric FR-betaL49A/FR-alpha constructs including progressively
shorter segments of FR-alpha downstream of position 92 as well as selected point
mutants were studied. Simultaneous substitution of Leu-49, Phe-104, and Gly-166
in FR-beta with the corresponding FR-alpha residues Ala, Val, and Glu,
respectively, reconstituted the ligand binding characteristics of FR-alpha. The
results also exclude a role for other residues in FR-alpha in determining its
functional divergence. A homology model of FR-alpha based on the three
dimensional structure of the chicken riboflavin-binding protein is used to show
the position of residues 49, 104, and 166 in relation to the hydrophobic cleft
corresponding to the riboflavin-binding pocket.
PMID- 10196193
TI - CheY-dependent methylation of the asparagine receptor, McpB, during chemotaxis in
Bacillus subtilis.
AB - For the Gram-positive organism Bacillus subtilis, chemotaxis to the attractant
asparagine is mediated by the chemoreceptor McpB. In this study, we show that
rapid net demethylation of B. subtilis McpB results in the immediate production
of methanol, presumably due to the action of CheB. We also show that net
demethylation of McpB occurs upon both addition and removal of asparagine. After
each demethylation event, McpB is remethylated to nearly prestimulus levels. Both
remethylation events are attributable to CheR using S-adenosylmethionine as a
substrate. Therefore, no methyl transfer to an intermediate carrier need be
postulated to occur during chemotaxis in B. subtilis as was previously suggested.
Furthermore, we show that the remethylation of asparagine-bound McpB requires the
response regulator, CheY-P, suggesting that CheY-P acts in a feedback mechanism
to facilitate adaptation to positive stimuli during chemotaxis in B. subtilis.
This hypothesis is supported by two observations: a cheRBCD mutant is capable of
transient excitation and subsequent oscillations that bring the flagellar
rotational bias below the prestimulus value in the tethered cell assay, and the
cheRBCD mutant is capable of swarming in a Tryptone swarm plate.
PMID- 10196194
TI - Del1 induces integrin signaling and angiogenesis by ligation of alphaVbeta3.
AB - Del1 is a novel extracellular matrix protein encoding three Notch-like epidermal
growth factor repeats, an RGD motif, and two discoidin domains. Del1 is expressed
in an endothelial cell-restricted pattern during early development. In studies
reported here, recombinant baculovirus Del1 protein was shown to promote
alphavbeta3-dependent endothelial cell attachment and migration. Attachment of
endothelial cells to Del1 was associated with clustering of alphavbeta3, the
formation of focal complexes, and recruitment of talin and vinculin into these
complexes. These events were shown to be associated with phosphorylation of
proteins in the focal complexes, including the time-dependent phosphorylation of
p125(FAK), MAPK, and Shc. When recombinant Del1 was evaluated in an in ovo chick
chorioallantoic membrane assay, it was found to have potent angiogenic activity.
This angiogenic activity was inhibited by a monoclonal antibody directed against
alphavbeta3, and an RAD mutant Del1 protein was inactive. Thus Del1 provides a
unique autocrine angiogenic pathway for the embryonic endothelium, and this
function is mediated in part by productive ligation of integrin alphavbeta3.
PMID- 10196195
TI - Mechanism of triclosan inhibition of bacterial fatty acid synthesis.
AB - Triclosan is a broad-spectrum antibacterial agent that inhibits bacterial fatty
acid synthesis at the enoyl-acyl carrier protein reductase (FabI) step.
Resistance to triclosan in Escherichia coli is acquired through a missense
mutation in the fabI gene that leads to the expression of FabI[G93V]. The
specific activity and substrate affinities of FabI[G93V] are similar to FabI. Two
different binding assays establish that triclosan dramatically increases the
affinity of FabI for NAD+. In contrast, triclosan does not increase the binding
of NAD+ to FabI[G93V]. The x-ray crystal structure of the FabI-NAD+-triclosan
complex confirms that hydrogen bonds and hydrophobic interactions between
triclosan and both the protein and the NAD+ cofactor contribute to the formation
of a stable ternary complex, with the drug binding at the enoyl substrate site.
These data show that the formation of a noncovalent "bi-substrate" complex
accounts for the effectiveness of triclosan as a FabI inhibitor and illustrates
that mutations in the FabI active site that interfere with the formation of a
stable FabI-NAD+-triclosan ternary complex acquire resistance to the drug.
PMID- 10196197
TI - The subcellular localization of SF2/ASF is regulated by direct interaction with
SR protein kinases (SRPKs).
AB - Serine/arginine-rich (SR) proteins play an important role in constitutive and
alternative pre-mRNA splicing. The C-terminal arginine-serine domain of these
proteins, such as SF2/ASF, mediates protein-protein interactions and is
phosphorylated in vivo. Using glutathione S-transferase (GST)-SF2/ASF-affinity
chromatography, the SF2/ASF kinase activity was co-purified from HeLa cells with
a 95-kDa protein, which was recognized by an anti-SR protein kinase (SRPK) 1
monoclonal antibody. Recombinant SRPK1 and SRPK2 bound to and phosphorylated GST
SF2/ASF in vitro. Phosphopeptide mapping showed that identical sites were
phosphorylated in the pull-down kinase reaction with HeLa extracts and by
recombinant SRPKs. Epitope-tagged SF2/ASF transiently expressed in COS7 cells co
immunoprecipitated with SRPKs. Deletion analysis mapped the phosphorylation sites
to a region containing an (Arg-Ser)8 repeat beginning at residue 204, and far
Western analysis showed that the region is required for binding of SRPKs to
SF2/ASF. Further binding studies showed that SRPKs bound unphosphorylated SF2/ASF
but did not bind phosphorylated SF2/ASF. Expression of an SRPK2 kinase-inactive
mutant caused accumulation of SF2/ASF in the cytoplasm. These results suggest
that the formation of complexes between SF2/ASF and SRPKs, which is influenced by
the phosphorylation state of SF2/ASF, may have regulatory roles in the assembly
and localization of this splicing factor.
PMID- 10196196
TI - SPI-B activates transcription via a unique proline, serine, and threonine domain
and exhibits DNA binding affinity differences from PU.1.
AB - SPI-B is a B lymphocyte-specific Ets transcription factor that shares a high
degree of similarity with PU.1/SPI-1. In direct contrast to PU.1(-/-) mice that
die in utero and lack monocytes, neutrophils, B cells, and T cells, Spi-B-/- mice
are viable and exhibit a severe B cell proliferation defect. Since PU.1 is
expressed at wild type levels in Spi-B-/- B cells, the mutant mice provide
genetic evidence that SPI-B and PU.1 have at least some non-redundant roles in B
lymphocytes. To begin to understand the molecular basis for these defects, we
delineated functional domains of SPI-B for comparison to those of PU.1. By using
a heterologous co-transfection system, we identified two independent
transactivation domains in the N terminus of SPI-B. Interestingly, only one of
these domains (amino acids 31-61), a proline/serine/threonine-rich region, unique
among Ets proteins, is necessary for transactivation of the immunoglobulin lambda
light chain enhancer. This transactivation motif is in marked contrast to PU.1,
which contains acidic and glutamine-rich domains. In addition, we describe a
functional PU.1 site within the c-FES promoter which SPI-B fails to bind
efficiently and transactivate. Finally, we show that SPI-B interacts with the
PU.1 cofactors Pip, TBP, c-Jun and with lower affinity to nuclear factor
interleukin-6beta and retinoblastoma. Taken together, these data suggest that SPI
B binds DNA with a different affinity for certain sites than PU.1 and harbors
different transactivation domains. We conclude that SPI-B may activate unique
target genes in B lymphocytes and interact with unique, although currently
unidentified, cofactors.
PMID- 10196198
TI - Functional-structural analysis of threonine 25, a residue coordinating the
nucleotide-bound magnesium in elongation factor Tu.
AB - Elongation factor (EF) Tu Thr-25 is a key residue binding the essential magnesium
complexed to nucleotide. We have characterized mutations at this position to the
related Ser and to Ala, which abolishes the bond to Mg2+, and a double mutation,
H22Y/T25S. Nucleotide interaction was moderately destabilized in EF-Tu(T25S) but
strongly in EF-Tu(T25A) and EF-Tu(H22Y/T25S). Binding Phe-tRNAPhe to
poly(U).ribosome needed a higher magnesium concentration for the latter two
mutants but was comparable at 10 mM MgCl2. Whereas EF-Tu(T25S) synthesized
poly(Phe), as effectively as wild type, the rate was reduced to 50% for EF
Tu(H22Y/T25S) and was, surprisingly, still 10% for EF-Tu(T25A). In contrast,
protection of Phe-tRNAPhe against spontaneous hydrolysis by the latter two
mutants was very low. The intrinsic GTPase in EF-Tu(H22Y/T25S) and (T25A) was
reduced, and the different responses to ribosomes and kirromycin suggest that
stimulation by these two agents follows different mechanisms. Of the mutants,
only EF-Tu(T25A) forms a more stable complex with EF-Ts than wild type. This
implies that stabilization of the EF-Tu.EF-Ts complex is related to the inability
to bind Mg2+, rather than to a decreased nucleotide affinity. These results are
discussed in the light of the three-dimensional structure. They emphasize the
importance of the Thr-25-Mg2+ bond, although its absence is compatible with
protein synthesis and thus with an active overall conformation of EF-Tu.
PMID- 10196199
TI - A phosphotransferase that generates phosphatidylinositol 4-phosphate (PtdIns-4-P)
from phosphatidylinositol and lipid A in Rhizobium leguminosarum. A membrane
bound enzyme linking lipid a and ptdins-4-p biosynthesis.
AB - Membranes of Rhizobium leguminosarum contain a 3-deoxy-D-manno-octulosonic acid
(Kdo)-activated lipid A 4'-phosphatase required for generating the unusual
phosphate-deficient lipid A found in this organism. The enzyme has been
solubilized with Triton X-100 and purified 80-fold. As shown by co-purification
and thermal inactivation studies, the 4'-phosphatase catalyzes not only the
hydrolysis of (Kdo)2-[4'-32P]lipid IVA but also the transfer the 4'-phosphate of
Kdo2-[4'-32P]lipid IVA to the inositol headgroup of phosphatidylinositol (PtdIns)
to generate PtdIns-4-P. Like the 4'-phosphatase, the phosphotransferase activity
is not present in Escherichia coli, Rhizobium meliloti, or the nodulation
defective mutant 24AR of R. leguminosarum. The specific activity for the
phosphotransferase reaction is about 2 times higher than that of the 4'
phosphatase. The phosphotransferase assay conditions are similar to those used
for PtdIns kinases, except that ATP and Mg2+ are omitted. The apparent Km for
PtdIns is approximately 500 microM versus 20-100 microM for most PtdIns kinases,
but the phosphotransferase specific activity in crude cell extracts is higher
than that of most PtdIns kinases. The phosphotransferase is absolutely specific
for the 4-position of PtdIns and is highly selective for PtdIns as the acceptor.
The 4'-phosphatase/phosphotransferase can be eluted from heparin- or Cibacron
blue-agarose with PtdIns. A phosphoenzyme intermediate may account for the dual
function of this enzyme, since a single 32P-labeled protein species (Mr
approximately 68,000) can be trapped and visualized by SDS gel electrophoresis of
enzyme preparations incubated with Kdo2-[4'-32P]lipid IVA. Although PtdIns is not
detected in cultures of R. leguminosarum/etli (CE3), PtdIns may be synthesized
during nodulation or supplied by plant membranes, given that soybean PtdIns is an
excellent phosphate acceptor. A bacterial enzyme for generating PtdIns-4-P and a
direct link between lipid A and PtdIns-4-P biosynthesis have not been reported
previously.
PMID- 10196201
TI - Temporal coordination between initiation of HIV (+)-strand DNA synthesis and
primer removal.
AB - In this study, we have analyzed the interdependence between the polymerase and
RNase H active sites of human immunodeficiency virus-1 reverse transcriptase (RT)
using an in vitro system that closely mimics the initiation of (+)-strand DNA
synthesis. Time course experiments show that RT pauses after addition of the 12th
DNA residue, and at this stage the RNase H activity starts to cleave the RNA
primer from newly synthesized DNA. Comparison of cleavage profiles obtained with
3'- and 5'-end-labeled primer strands indicates that RT now translocates in the
opposite direction, i.e. in the 5' direction of the RNA strand. DNA synthesis
resumes again in the 3' direction, after the RNA-DNA junction was efficiently
cleaved. Moreover, we further characterized complexes generated before, during,
and after position +12, by treating these with Fe2+ to localize the RNase H
active site on the DNA template. Initially, when RT binds the RNA/DNA substrate,
oxidative strand breaks were seen at a distance of 18 base pairs upstream from
the primer terminus, whereas 17 base pairs were observed at later stages when the
enzyme binds more and more DNA/DNA. These data show that the initiation of (+)
strand synthesis is accompanied by a conformational change of the polymerase
competent complex.
PMID- 10196200
TI - A deacylase in Rhizobium leguminosarum membranes that cleaves the 3-O-linked beta
hydroxymyristoyl moiety of lipid A precursors.
AB - Lipid A from the nitrogen-fixing bacterium Rhizobium leguminosarum displays many
structural differences compared with lipid A of Escherichia coli. R.
leguminosarum lipid A lacks the usual 1- and 4'-phosphate groups but is
derivatized with a galacturonic acid substituent at position 4'. R. leguminosarum
lipid A often contains an aminogluconic acid moiety in place of the proximal
glucosamine 1-phosphate unit. Striking differences also exist in the secondary
acyl chains attached to E. coli versus R. leguminosarum lipid A, specifically the
presence of 27-hydroxyoctacosanoate and the absence of laurate and myristate in
R. leguminosarum. Recently, we have found that lipid A isolated by pH 4.5
hydrolysis of R. leguminosarum cells is more heterogeneous than previously
reported (Que, N. L. S., Basu, S. S., White, K. A., and Raetz, C. R. H. (1998)
FASEB J. 12, A1284 (abstr.)). Lipid A species lacking the 3-O-linked beta
hydroxymyristoyl residue on the proximal unit contribute to this heterogeneity.
We now describe a membrane-bound deacylase from R. leguminosarum that removes a
single ester-linked beta-hydroxymyristoyl moiety from some lipid A precursors,
including lipid X, lipid IVA, and (3-deoxy-D-manno-octulosonic acid)2-lipid IVA.
The enzyme does not cleave E. coli lipid A or lipid A precursors containing an
acyloxyacyl moiety on the distal glucosamine unit. The enzyme is not present in
extracts of E. coli or Rhizobium meliloti, but it is readily demonstrable in
membranes of Pseudomonas aeruginosa, which also contains a significant proportion
of 3-O-deacylated lipid A species. Optimal reaction rates are seen between pH 5.5
and 6.5. The enzyme requires a nonionic detergent and divalent metal ions for
activity. It cleaves the monosaccharide lipid X at about 5% the rate of lipid IVA
and (3-deoxy-D-manno-octulosonic acid)2-lipid IVA. 1H NMR spectroscopy of the
deacylase reaction product, generated with lipid IVA as the substrate, confirms
unequivocally that the enzyme cleaves only the ester-linked beta-hydroxymyristoyl
residue at the 3-position of the glucosamine disaccharide.
PMID- 10196202
TI - The role of GMXCXXC metal binding sites in the copper-induced redistribution of
the Menkes protein.
AB - The Menkes protein (MNK or ATP7A) is a transmembrane, copper-transporting CPX
type ATPase, a subgroup of the extensive family of P-type ATPases. A striking
feature of the protein is the presence of six metal binding sites (MBSs) in the N
terminal region with the highly conserved consensus sequence GMXCXXC. MNK is
normally located in the trans-Golgi network (TGN) but has been shown to
relocalize to the plasma membrane when cells are cultured in media containing
high concentrations of copper. The experiments described in this report test the
hypothesis that the six MBSs are required for this copper-induced trafficking of
MNK. Site-directed mutagenesis was used to convert both cysteine residues in the
conserved MBS motifs to serines. Mutation of MBS 1, MBS 6, and MBSs 1-3 resulted
in a molecule that appeared to relocalize normally with copper, but when MBSs 4-6
or MBSs 1-6 were mutated, MNK remained in the TGN, even when cells were exposed
to 300 microM copper. Furthermore, the ability of the MNK variants to relocalize
corresponded well with their ability to confer copper resistance. To further
define the critical motifs, MBS 5 and MBS 6 were mutated, and these changes
abolished the response to copper. The region from amino acid 8 to amino acid 485
was deleted, resulting in mutant MNK that lacked 478 amino acids from the N
terminal region, including the first four MBSs. This truncated molecule responded
normally to copper. Moreover, when either one of the remaining MBS 5 and MBS 6
was mutated to GMXSXXS, the resulting proteins were localized to the TGN in low
copper and relocalized in response to elevated copper. These experiments
demonstrated that the deleted N-terminal region from amino acid 8 to amino acid
485 was not essential for copper-induced trafficking and that one MBS close to
the membrane channel of MNK was necessary and sufficient for the copper-induced
redistribution.
PMID- 10196204
TI - Identification of the APS protein as a novel insulin receptor substrate.
AB - In order to identify novel substrates involved in insulin receptor signaling, a
yeast two-hybrid 3T3-L1 adipocyte cDNA library was screened with the cytoplasmic
domain of the human insulin receptor as bait. Here we describe the isolation and
characterization of an interacting protein, APS, which contains pleckstrin
homology and Src homology 2 domains and several potential tyrosine
phosphorylation sites. APS mRNA and protein are expressed primarily in skeletal
muscle, heart, and adipose tissue, and in differentiated 3T3-L1 adipocytes. We
show that APS associates with phosphotyrosines situated within the activation
loop of the insulin receptor via the APS Src homology 2 domain. Insulin
stimulation of 3T3-L1 adipocytes resulted in rapid tyrosine phosphorylation of
endogenous APS on tyrosine 618, whereas platelet-derived growth factor treatment
resulted in no APS phosphorylation. In summary, we have identified a new insulin
receptor substrate that is primarily expressed in insulin-responsive tissues and
in 3T3-L1 adipocytes whose phosphorylation shows insulin receptor specificity.
These findings suggest a potential role for APS in insulin-regulated metabolic
signaling pathways.
PMID- 10196203
TI - The extracellular signal-regulated kinase pathway is required for activation
induced cell death of T cells.
AB - T cells can undergo activation-induced cell death (AICD) upon stimulation of the
T cell receptor-CD3 complex. We found that the extracellular signal-regulated
kinase (ERK) pathway is activated during AICD. Transient transfection of a
dominant interfering mutant of mitogen-activated/extracellular signal-regulated
receptor protein kinase kinase (MEK1) demonstrated that down-regulation of the
ERK pathway inhibited FasL expression during AICD, whereas activation of the ERK
pathway with a constitutively active MEK1 resulted in increased expression of
FasL. We also found that pretreatment with the specific MEK1 inhibitor PD98059
prevented the induction of FasL expression during AICD and inhibited AICD.
However, PD98059 had no effect on other apoptotic stimuli. We found only very
weak ERK activity during Fas-mediated apoptosis (induced by Fas cross-linking).
Furthermore, preincubation with the MEK1 inhibitor did not inhibit Fas-mediated
apoptosis. Finally, we also demonstrated that pretreatment with the MEK1
inhibitor could delay and decrease the expression of the orphan nuclear steroid
receptor Nur77, which has been shown to be essential for AICD. In conclusion,
this study demonstrates that the ERK pathway is required for AICD of T cells and
appears to regulate the induction of Nur77 and FasL expression during AICD.
PMID- 10196205
TI - Identification of a nuclear targeting domain in the insertion between helices C
and D in protease inhibitor-10.
AB - Protease inhibitor 10 (PI-10), an intracellular ovalbumin-serpin, contains a
series of basic amino acids in the loop between helices C and D that exhibit
homology to known nuclear targeting signals. Transfection of HeLa cells with
plasmids encoding enhanced green fluorescent protein (EGFP) coupled to PI-10
revealed an intense fluorescence of the nucleus. Immunoblotting demonstrated a
single Mr 80,000 EGFP.PI-10 complex in isolated nuclei. Mutation of four basic
amino acids in the interhelical loop to alanines (i.e. K74A, K75A, R76A, K77A)
resulted in the fluorescent complex being confined to the cytoplasm. Further
evidence for a nuclear targeting signal in this region was provided by
localization of the fluorescent label to the nucleus in cells transfected with a
plasmid encoding EGFP fused to the 25 amino acids comprising the interhelical
loop of PI-10 (i.e. Arg-63 to Glu-87), whereas a cytoplasmic distribution was
noted for the construct encoding EGFP coupled to the mutated interhelical loop.
These data raise the possibility that PI-10 may play a role in regulating
protease activity within the nucleus, a property unique in the field of serpin
biology.
PMID- 10196206
TI - Transcomplementation between different types of respiration-deficient
mitochondria with different pathogenic mutant mitochondrial DNAs.
AB - Two cell lines were used for determination of whether interaction occurred
between different types of respiration-deficient mitochondria. One was a
respiration-deficient rho- cell line having mutant mitochondrial DNA (mtDNA) with
a 5,196-base pair deletion including five tRNA genes (tRNAGly, Arg, Ser(AGY),
Leu(CUN), His), DeltamtDNA5196, causing Kearns-Sayre syndrome. The other was a
respiration-deficient syn- cell line having mutant mtDNA with an A to G
substitution at 4,269 in the tRNAIle gene, mtDNA4269, causing fatal
cardiomyopathy. The occurrence of mitochondrial interaction was examined by
determining whether cybrids constructed by fusion of enucleated rho- cells with
syn- cells became respiration competent by exchanging their tRNAs. No cybrids
were isolated in selection medium, where only respiration-competent cells could
survive, suggesting that no interaction occurred, or that it occurred so slowly
that sufficient recovery of mitochondrial respiratory function was not attained
by the time of selection. The latter possibility was confirmed by the
observations that heteroplasmic cybrids with both mutant mtDNA4269 and
DeltamtDNA5196 isolated without selection showed restored mitochondrial
respiration activity. This demonstration of transcomplementation between
different respiration-deficient mitochondria will help in understanding the
relationship between somatic mutant mtDNAs and the roles of such mutations in
aging processes.
PMID- 10196207
TI - Inhibitory modulation of B cell receptor-mediated Ca2+ mobilization by Src
homology 2 domain-containing inositol 5'-phosphatase (SHIP).
AB - Src homology 2 domain-containing inositol 5'-phosphatase (SHIP) mediates
inhibitory signals that attenuate intracellular Ca2+ mobilization in B cells upon
B cell receptor (BCR) stimulation. To clarify the mechanisms affected by SHIP, we
analyzed Ca2+ mobilization in the DT40 B cell line in which the SHIP gene was
disrupted. In SHIP-deficient cells, Ca2+ transient elicited by BCR stimulation
was more prolonged than that in control cells both in the presence and absence of
extracellular Ca2+. Inositol 1,4, 5-trisphosphate production following BCR
stimulation was enhanced in SHIP-deficient cells. In SHIP-deficient cells in
comparison with the control cells, BCR stimulation in the absence of
extracellular Ca2+ induced a greater degree of Ca2+ store depletion and the Ca2+
influx upon re-addition of extracellular Ca2+ was also greater. However, store
operated Ca2+ influx (SOC) elicited by thapsigargin-induced store depletion was
not affected by SHIP. These results indicate that the primary target pathway of
SHIP is the Ca2+ release from the stores, and that Ca2+ influx by the SOC
mechanism is secondarily controlled by the level of Ca2+ in the stores without
direct inhibition of SOC. In this way, SHIP may play an important role in
ensuring the robust tuning of Ca2+ signaling in B cells.
PMID- 10196208
TI - Integrin-mediated migration of murine B82L fibroblasts is dependent on the
expression of an intact epidermal growth factor receptor.
AB - To evaluate the mechanisms by which epidermal growth factor (EGF) regulates actin
based cellular processes such as cell migration, we first examined the effects of
EGF on cell adhesion, which is essential for cell migration. In mouse B82L
fibroblasts transfected with the full-length EGF receptor, EGF promotes cell
rounding and attenuates cell spreading on fibronectin, laminin, and vitronectin,
and thus appears to reduce the strength of cell adhesion. Moreover, EGF
synergizes with multiple extracellular matrix (ECM) components in the promotion
of integrin-mediated cell migration of several different cell types, including
fibroblasts and various carcinoma and osteosarcoma cell lines. Interestingly, co
presentation (co-positioning) of EGF with laminin or fibronectin is essential for
EGF-stimulated migration. When EGF is mixed with the cells instead of the ECM
components, it has little effect on cell migration. These results suggest that co
presentation of EGF with ECM components can enhance the polarization events
required for directional cell movement. To identify the EGF receptor elements
critical for the EGF stimulation of cell migration, B82L fibroblasts were
transfected with either mutated or wild-type EGF receptors. Surprisingly, we
found that B82L-Parental cells that lack the EGF receptor are not able to migrate
to fibronectin, even though they can adhere to fibronectin. However, the
introduction of wild-type EGF receptors into these fibroblasts enables them to
migrate toward fibronectin even in the absence of EGF. The requirement of the EGF
receptor for cell migration does not appear to result from the secretion of EGF
or TGF-alpha by the cells transfected with the EGF receptor. Furthermore, cells
expressing EGF receptors that are kinase-inactive, or C-terminally truncated,
exhibit little migration toward fibronectin, indicating that an intact EGF
receptor kinase is required for fibronectin-induced cell migration. In addition,
neutralizing anti-EGF receptor antibodies attenuate cell migration in the
presence of EGF, and inhibit migration to fibronectin or laminin alone. These
results further suggest that the EGF receptor is downstream of integrin
activation in the signal transduction pathways leading to fibroblast migration.
PMID- 10196209
TI - Cloning of the cyclin A1 genomic structure and characterization of the promoter
region. GC boxes are essential for cell cycle-regulated transcription of the
cyclin A1 gene.
AB - Cyclin A1 is a recently cloned cyclin with high level expression in meiotic cells
in the testis. However, it is also frequently expressed at high levels in acute
myeloid leukemia. To elucidate the regulation of cyclin A1 gene expression, we
cloned and analyzed the genomic structure of cyclin A1. It consists of 9 exons
within 13 kilobase pairs. The TATA-less promoter initiates transcription from
several start sites with the majority of transcripts beginning within a 4-base
pair stretch. A construct containing a fragment from -190 to +145 showed the
highest transcriptional activity. Transfection of cyclin A1 promoter constructs
into S2 Drosophila cells demonstrated that Sp1 is essential for the activity of
the promoter. Sp1, as well as Sp3, bound to four GC boxes between nucleotides
130 and -80 as observed by gel shift analysis. Mutations in two or more of the
four GC boxes decreased promoter activity by >80%. The promoter was found to be
cell cycle-regulated with highest activities found in late S and G2/M phase.
Further analyses suggested that cell cycle regulation was accomplished by
periodic repression of the GC boxes in G1 phase. Taken together, our data show
that cyclin A1 promoter activity critically depends on four GC boxes, and members
of the Sp1 family appear to be involved in directing expression of cyclin A1 in
both a tissue- and cell cycle-specific manner.
PMID- 10196210
TI - The roles of 5'-HS2, 5'-HS3, and the gamma-globin TATA, CACCC, and stage selector
elements in suppression of beta-globin expression in early development.
AB - The roles of HS2 and HS3 from the human beta-globin locus control region and of
the TATA, CACCC, and stage selector elements of the gamma-globin promoter, in
competitive inhibition of beta-globin gene expression in early development, were
tested using stable transfections of HEL and K562 cells. Cells with an HS3gamma
beta construct demonstrate that HS3 exhibits enhancing activity, but compared
with HS2, this site participates less consistently in the inhibition of
embryonic/fetal beta-globin expression. In cells with HS3HS2gamma beta
constructs, the two HS sites act in concert to more effectively enhance gamma
globin gene expression and to drive stage-specific expression of the gamma- and
beta-globin genes. A gamma-globin gene with a -161 promoter can competitively
inhibit beta-globin gene expression. HS3HS2gamma beta constructs were used to
determine the effects of gamma-globin promoter mutations within this region on
competition. The CACCC and TATA elements, but not the stage selector element,
inhibit inappropriate embryonic/fetal stage expression of the beta-globin gene.
The mutation in the gamma-globin TATA element results in the use of two major
alternative transcription start sites. The data suggest that proteins binding to
the gamma-globin CACCC and TATA elements interact with those binding to HS2
and/or HS3 to preclude beta-globin transcription in early development.
PMID- 10196211
TI - Recombinant glycoproteins that inhibit complement activation and also bind the
selectin adhesion molecules.
AB - Soluble human complement receptor type 1 (sCR1, TP10) has been expressed in
Chinese hamster ovary (CHO) DUKX-B11 cells and shown to inhibit the classical and
alternative complement pathways in vitro and in vivo. A truncated version of sCR1
lacking the long homologous repeat-A domain (LHR-A) containing the C4b binding
site has similarly been expressed and designated sCR1[desLHR-A]. sCR1[desLHR-A]
was shown to be a selective inhibitor of the alternative complement pathway in
vitro and to function in vivo. In this study, sCR1 and sCR1[desLHR-A] were
expressed in CHO LEC11 cells with an active alpha(1,3)-fucosyltransferase, which
makes possible the biosynthesis of the sialyl-Lewisx (sLex) tetrasaccharide
(NeuNAcalpha2-3Galbeta1-4(Fucalpha1-3)GlcNAc) during post-translational
glycosylation. The resulting glycoproteins, designated sCR1sLex and sCR1[desLHR
A]sLex, respectively, retained the complement regulatory activities of their DUKX
B11 counterparts, which lack alpha(1-3)-fucose. Carbohydrate analysis of purified
sCR1sLex and sCR1[desLHR-A]sLex indicated an average incorporation of 10 and 8
mol of sLex/mol of glycoprotein, respectively. sLex is a carbohydrate ligand for
the selectin adhesion molecules. sCR1sLex was shown to specifically bind CHO
cells expressing cell surface E-selectin. sCR1[desLHR-A]sLex inhibited the
binding of the monocytic cell line U937 to human aortic endothelial cells, which
had been activated with tumor necrosis factor-alpha to up-regulate the expression
of E-selectin. sCR1sLex inhibited the binding of U937 cells to surface-adsorbed P
selectin-IgG. sCR1sLex and sCR1[desLHR-A]sLex have thus demonstrated both
complement regulatory activity and the capacity to bind selectins and to inhibit
selectin-mediated cell adhesion in vitro.
PMID- 10196212
TI - The role of antiapoptotic Bcl-2 family members in endothelial apoptosis
elucidated with antisense oligonucleotides.
AB - In this study, we utilized potent antisense oligonucleotides to examine the role
of two Bcl-2 family members found in human umbilical vein endothelial cells
(HUVEC). The first, A1, is thought to be a TNF-alpha-inducible cytoprotective
gene, and the second, Bcl-XL, is constitutively expressed. Inhibition of the
constitutive levels of Bcl-XL caused 10-25% of the cell population to undergo
apoptosis and increased the susceptibility of cells to treatment with low
concentrations of staurosporin or ceramide. The caspase inhibitor
benzyloxycarbonyl-Val-Ala-Asp(OMe)-CH2 prevented DNA fragmentation and DeltaYm
loss caused by Bcl-XL inhibition or Bcl-XL inhibition combined with staurosporin.
However, disruption of DeltaYm caused by Bcl-XL inhibition combined with ceramide
treatment was not inhibited by benzyloxycarbonyl-Val-Ala-Asp(OMe)-CH2, although
DNA fragmentation was completely prevented. Taken together, these results
demonstrate a direct protective role for Bcl-XL under normal resting conditions
and under low level apoptotic challenges to HUVEC. Furthermore, Bcl-XL protects
cells from caspase-dependent and -independent mechanisms of DeltaYm disruption.
In contrast to Bcl-XL, A1 inhibition did not show a marked effect on the
susceptibility of HUVEC to undergo apoptosis in response to TNF-alpha, ceramide,
or staurosporin. These results demonstrate that although A1 may be a
cytoprotective gene induced by TNF-alpha, it is not primarily responsible for
HUVEC resistance to this cytokine.
PMID- 10196213
TI - Role of arrestins in endocytosis and signaling of alpha2-adrenergic receptor
subtypes.
AB - We investigated the role of arrestins in the trafficking of human alpha2
adrenergic receptors (alpha2-ARs) and the effect of receptor trafficking on
p42/p44 MAP kinase activation. alpha2-ARs expressed in COS-1 cells demonstrated a
modest level of agonist-mediated internalization, with alpha2c > alpha2b >
alpha2a. However, upon coexpression of arrestin-2 (beta-arrestin-1) or arrestin-3
(beta-arrestin-2), internalization of the alpha2b AR was dramatically enhanced
and redistribution of receptors to clathrin coated vesicles and endosomes was
observed. Internalization of the alpha2c AR was selectively promoted by
coexpression of arrestin-3, while alpha2a AR internalization was only slightly
stimulated by coexpression of either arrestin. Coexpression of GRK2 had no effect
on the internalization of any alpha2-AR subtype, either in the presence or
absence of arrestins. Internalization of the alpha2b and alpha2c ARs was
inhibited by coexpression of dominant negative dynamin-K44A. However, alpha2-AR
mediated activation of either endogenous or cotransfected p42/p44 mitogen
activated protein (MAP) kinase was not affected by either dynamin-K44A or
arrestin-3. Moreover, activation of p42/p44 MAP kinase by endogenous epidermal
growth factor, lysophosphatidic acid, and beta2-adrenergic receptors was also
unaltered by dynamin-K44A. In summary, our data suggest that internalization of
the alpha2b, alpha2c, and to a lesser extent alpha2a ARs, is both arrestin- and
dynamin-dependent. However, endocytosis does not appear to be required for alpha2
adrenergic, epidermal growth factor, lysophosphatidic acid, or beta2-adrenergic
receptor-mediated p42/p44 MAP kinase activation in COS-1 cells.
PMID- 10196214
TI - Vitamin D-dependent suppression of human atrial natriuretic peptide gene promoter
activity requires heterodimer assembly.
AB - Crystallographic structures of the ligand-binding domains for the retinoid X
(RXR) and estrogen receptors have identified conserved surface residues that
participate in dimer formation. Homologous regions have been identified in the
human vitamin D receptor (hVDR). Mutating Lys-386 to Ala (K386A) in hVDR
significantly reduced binding to glutathione S-transferase-RXRalpha in solution,
whereas binding of an I384R/Q385R VDR mutant was almost undetectable. The K386A
mutant formed heterodimers with RXRalpha on DR-3 (a direct repeat of AGGTCA
spaced by three nucleotides), whereas the I384R/Q385R mutant completely
eliminated heterodimer formation. Wild type hVDR effected a 3-fold induction of
DR-3-dependent thymidine kinase-luciferase activity in cultured neonatal rat
atrial myocytes, an effect that was increased to 8-9-fold by cotransfected
hRXRalpha. Induction by K386A, in the presence or absence of RXRalpha, was only
slightly lower than that seen with wild type VDR. On the other hand, I384R/Q385R
alone displayed no stimulatory activity and less than 2-fold induction in the
presence of hRXRalpha. Qualitatively similar findings were observed with the
negative regulation of the human atrial natriuretic peptide gene promoter by
these mutants. Collectively, these studies identify specific amino acids in hVDR
that play a critical role in heterodimer formation and subsequent modulation of
gene transcription.
PMID- 10196215
TI - The goodpasture autoantigen. Mapping the major conformational epitope(s) of
alpha3(IV) collagen to residues 17-31 and 127-141 of the NC1 domain.
AB - The Goodpasture (GP) autoantigen has been identified as the alpha3(IV) collagen
chain, one of six homologous chains designated alpha1-alpha6 that comprise type
IV collagen (Hudson, B. G., Reeders, S. T., and Tryggvason, K. (1993) J. Biol.
Chem. 268, 26033-26036). In this study, chimeric proteins were used to map the
location of the major conformational, disulfide bond-dependent GP autoepitope(s)
that has been previously localized to the noncollagenous (NC1) domain of
alpha3(IV) chain. Fourteen alpha1/alpha3 NC1 chimeras were constructed by
substituting one or more short sequences of alpha3(IV)NC1 at the corresponding
positions in the non-immunoreactive alpha1(IV)NC1 domain and expressed in
mammalian cells for proper folding. The interaction between the chimeras and
eight GP sera was assessed by both direct and inhibition enzyme-linked
immunosorbent assay. Two chimeras, C2 containing residues 17-31 of alpha3(IV)NC1
and C6 containing residues 127-141 of alpha3(IV)NC1, bound autoantibodies, as did
combination chimeras containing these regions. The epitope(s) that encompasses
these sequences is immunodominant, showing strong reactivity with all GP sera and
accounting for 50-90% of the autoantibody reactivity toward alpha3(IV)NC1. The
conformational nature of the epitope(s) in the C2 and C6 chimeras was established
by reduction of the disulfide bonds and by PEPSCAN analysis of overlapping 12-mer
peptides derived from alpha1- and alpha3(IV)NC1 sequences. The amino acid
sequences 17-31 and 127-141 in alpha3(IV)NC1 have thus been shown to contain the
critical residues of one or two disulfide bond-dependent conformational
autoepitopes that bind GP autoantibodies.
PMID- 10196216
TI - Interaction between the nucleotide exchange factor Mge1 and the mitochondrial
Hsp70 Ssc1.
AB - Function of Hsp70s such as DnaK of the Escherichia coli cytoplasm and Ssc1 of the
mitochondrial matrix of Saccharomyces cerevisiae requires the nucleotide release
factors, GrpE and Mge1, respectively. A loop, which protrudes from domain IA of
the DnaK ATPase domain, is one of six sites of interaction revealed in the
GrpE:DnaK co-crystal structure and has been implicated as a functionally
important site in both DnaK and Ssc1. Alanine substitutions for the amino acids
(Lys-108 and Arg-213 of Mge1) predicted to interact with the Hsp70 loop were
analyzed. Mge1 having both substitutions was able to support growth in the
absence of the essential wild-type protein. K108A/R213A Mge1 was able to
stimulate nucleotide release from Ssc1 and function in refolding of denatured
luciferase, albeit higher concentrations of mutant protein than wild-type protein
were required. In vitro and in vivo assays using K108A/R213A Mge1 and Ssc1
indicated that the disruption of contact at this site destabilized the
interaction between the two proteins. We propose that the direct interaction
between the loop of Ssc1 and Mge1 is not required to effect nucleotide release
but plays a role in stabilization of the Mge1-Ssc1 interaction. The robust growth
of the K108A/R213A MGE1 mutant suggests that the interaction between Mge1 and
Ssc1 is tighter than required for function in vivo.
PMID- 10196217
TI - Evidence of interactions between the nucleocapsid protein NCp7 and the reverse
transcriptase of HIV-1.
AB - The human immunodeficiency virus (HIV-1) nucleocapsid protein NCp7 containing two
CX2CX4HX4C-type zinc fingers was proposed to be involved in reverse transcriptase
(RT)-catalyzed proviral DNA synthesis through promotion of tRNA3Lys annealing to
the RNA primer binding site, improvement of DNA strand transfers, and enhancement
of RT processivity. The NCp7 structural characteristics are crucial because
mutations altering the finger domain conformation led to noninfectious viruses
characterized by defects in provirus integration. These findings prompted us to
study a putative RT/NCp7 protein-protein interaction. Binding assays using far
Western analysis or RT immobilized on beads clearly showed the formation of a
complex between NCp7 and RT. The affinity of NCp7 for p66/p51RT was 0.60 microM
with a 1:1 stoechiometry. This interaction was confirmed by chemical cross
linking and co-immunoprecipitation of the two proteins in a viral environment.
Competition experiments using different NCp7 mutants showed that alteration of
the finger structure disrupted RT recognition, giving insights into the loss of
infectivity of corresponding HIV-1 mutants. Together with structural data on RT,
these results suggest that the role of NCp7 could be to enhance RT processivity
through stabilization of a p51-induced active form of the p66 subunit and open
the way for designing new antiviral agents.
PMID- 10196218
TI - Dual mechanisms of regulation of Na/H exchanger NHE-3 by parathyroid hormone in
rat kidney.
AB - Parathyroid hormone (PTH) is a potent inhibitor of mammalian renal proximal
tubule sodium absorption via suppression of the apical membrane Na/H exchanger
(NHE-3). We examined the mechanisms by which PTH inhibits NHE-3 activity by
giving an acute intravenous PTH bolus to parathyroidectomized rats.
Parathyroidectomy per se increased apical membrane NHE-3 activity and antigen.
Acute infusion of PTH caused a time-dependent decrease in NHE-3 activity as early
as 30 min. Decrease in NHE-3 activity at 30 and 60 min was accompanied by
increased NHE-3 phosphorylation. In contrast to the rapid changes in NHE-3
activity and phosphorylation, decrease in apical membrane NHE-3 antigen was not
detectable until 4-12 h after the PTH bolus. The decrease in apical membrane NHE
3 occurred in the absence of changes in total renal cortical NHE-3 antigen.
Pretreatment of the animals with the microtubule-disrupting agent colchicine
blocked the PTH-induced decrease in apical NHE-3 antigen. We propose that PTH
acutely cause a decrease in NHE-3 intrinsic transport activity possibly via a
phosphorylation-dependent mechanism followed by a decrease in apical membrane NHE
3 antigen via changes in protein trafficking.
PMID- 10196219
TI - Disruption of YHC8, a member of the TSR1 gene family, reveals its direct
involvement in yeast protein translocation.
AB - Genetic studies of Saccharomyces cerevisiae have identified many components
acting to deliver specific proteins to their cellular locations. Genome analysis,
however, has indicated that additional genes may also participate in such protein
trafficking. The product of the yeast Yarrowia lipolytica TSR1 gene promotes the
signal recognition particle-dependent translocation of secretory proteins through
the endoplasmic reticulum. Here we describe the identification of a new gene
family of proteins that is well conserved among different yeast species. The TSR1
genes encode polypeptides that share the same protein domain distribution and,
like Tsr1p, may play an important role in the early steps of the signal
recognition particle-dependent translocation pathway. We have identified five
homologues of the TSR1 gene, four of them from the yeast Saccharomyces cerevisiae
and the other from Hansenula polymorpha. We generated a null mutation in the S.
cerevisiae YHC8 gene, the closest homologue to Y. lipolytica TSR1, and used
different soluble (carboxypeptidase Y, alpha-factor, invertase) and membrane
(dipeptidyl-aminopeptidase) secretory proteins to study its phenotype. A large
accumulation of soluble protein precursors was detected in the mutant strain.
Immunofluorescence experiments show that Yhc8p is localized in the endoplasmic
reticulum. We propose that the YHC8 gene is a new and important component of the
S. cerevisiae endoplasmic reticulum membrane and that it functions in protein
translocation/insertion of secretory proteins through or into this compartment.
PMID- 10196220
TI - Expression, purification, and biochemical characterization of the amino-terminal
extracellular domain of the human calcium receptor.
AB - We purified the extracellular domain (ECD) of the human calcium receptor (hCaR)
from the medium of HEK-293 cells stably transfected with a hCaR cDNA containing
an isoleucine 599 nonsense mutation. A combination of lectin, anion exchange, and
gel permeation chromatography yielded milligram quantities of >95% pure protein
from 15 liters of starting culture medium. The purified ECD ran as an
approximately 78-kDa protein on SDS-polyacrylamide gel electrophoresis and was
found to be a disulfide-linked dimer. Its NH2-terminal sequence, carbohydrate
content, and CD spectrum were defined. Tryptic proteolysis studies showed two
major sites accessible to cleavage. These studies provide new insights into the
structure of the hCaR ECD. Availability of purified ECD protein should permit
further structural studies to help define the mechanism of Ca2+ activation of
this G protein-coupled receptor.
PMID- 10196221
TI - CD40 ligand mutants responsible for X-linked hyper-IgM syndrome associate with
wild type CD40 ligand.
AB - CD40 ligand (CD40L) is a 33-kDa type II membrane glycoprotein mainly expressed on
activated CD4(+) T cells in trimeric form. When it is mutated, the clinical
consequences are X-linked hyper-IgM syndrome (XHIM), a primary immunodeficiency
disorder characterized by low levels of IgG, IgA, and elevated or normal levels
of IgM. Mutated CD40L can no longer bind CD40 nor provide signals for B cells to
proliferate and to switch from IgM to other immunoglobulin isotypes. When
considering gene therapy for XHIM, it is important to address the possibility
that the mutated CD40L associates with transduced wild type CD40L, and as a
consequence, immune reconstitution is not attained. In this study, we demonstrate
that the various mutated CD40L species we have identified in patients with XHIM,
including both full-length and truncated mutants, associate with wild type CD40L
on the cell surface of co-transfected COS cells. The association between wild
type and mutated CD40L was also observed in CD4(+) T cell lines established from
XHIM patients with leaky splice site mutations. The clinical phenotype of these
patients suggests that this association between wild type and mutated CD40L
species may result in less efficient cross-linking of CD40.
PMID- 10196222
TI - Brain-derived neurotrophic factor induces phosphorylation of fibroblast growth
factor receptor substrate 2.
AB - Brain-derived neurotrophic factor (BDNF) promotes neuronal survival. Gaining an
understanding of how BDNF, via the tropomyosin-related kinase B (TRKB) receptor,
elicits specific cellular responses is of contemporary interest. Expression of
mutant TrkB in fibroblasts, where tyrosine 484 was changed to phenylalanine,
abrogated Shc association with TrkB, but only attenuated and did not block BDNF
induced phosphorylation of mitogen-activated protein kinase (MAPK). This suggests
there is another BDNF-induced signaling mechanism for activating MAPK, which
compelled a search for other TrkB substrates. BDNF induces phosphorylation of
fibroblast growth factor receptor substrate 2 (FRS2) in both fibroblasts
engineered to express TrkB and human neuroblastoma (NB) cells that naturally
express TrkB. Additionally, BDNF induces phosphorylation of FRS2 in primary
cultures of cortical neurons, thus showing that FRS2 is a physiologically
relevant substrate of TrkB. Data are presented demonstrating that BDNF induces
association of FRS2 with growth factor receptor-binding protein 2 (GRB2) in
cortical neurons, fibroblasts, and NB cells, which in turn could activate the
RAS/MAPK pathway. This is not dependent on Shc, since BDNF does not induce
association of Shc and FRS2. Finally, the experiments suggest that FRS2 and suc
associated neurotrophic factor-induced tyrosine-phosphorylated target are the
same protein.
PMID- 10196223
TI - Role of clathrin-mediated endocytosis in CXCR2 sequestration, resensitization,
and signal transduction.
AB - CXCR2 is a seven-transmembrane receptor that transduces intracellular signals in
response to the chemokines interleukin-8, melanoma growth-stimulatory
activity/growth-regulatory protein, and other ELR motif-containing CXC chemokines
by coupling to heterotrimeric GTP-binding proteins. In this study, we explored
the mechanism responsible for ligand-induced CXCR2 endocytosis. Here, we
demonstrate that dynamin, a component of clathrin-mediated endocytosis, is
essential for CXCR2 endocytosis and resensitization. In HEK293 cells, dynamin I
K44A, a dominant-negative mutant of dynamin that inhibits the clathrin-mediated
endocytosis, blocks the ligand-stimulated CXCR2 sequestration. Furthermore, co
expression of dynamin I K44A significantly delays dephosphorylation of CXCR2
after ligand stimulation, suggesting that clathrin-mediated endocytosis plays an
important role in receptor dephosphorylation and resensitization. In addition,
ligand-mediated receptor down-regulation is attenuated when receptor
internalization is inhibited by dynamin I K44A. Interestingly, inhibition of
receptor endocytosis by dynamin I K44A does not affect the CXCR2-mediated
stimulation of mitogen-activated protein kinase. Most significantly, our data
indicate that the ligand-stimulated receptor endocytosis is required for CXCR2
mediated chemotaxis in HEK293 cells. Taken together, our findings suggest that
clathrin-mediated CXCR2 internalization is crucial for receptor endocytosis,
resensitization, and chemotaxis.
PMID- 10196224
TI - Binding of CtIP to the BRCT repeats of BRCA1 involved in the transcription
regulation of p21 is disrupted upon DNA damage.
AB - Mutations in BRCA1 are responsible for nearly all of the hereditary ovarian and
breast cancers, and about half of those in breast cancer-only kindreds. The
ability of BRCA1 to transactivate the p21 promoter can be inactivated by mutation
of the conserved BRCA1 C-terminal (BRCT) repeats. To explore the mechanisms of
this BRCA1 function, the BRCT repeats were used as bait in a yeast two-hybrid
screen. A known protein, CtIP, a co-repressor with CtBP, was found. CtIP
interacts specifically with the BRCT repeats of BRCA1, both in vitro and in vivo,
and tumor-derived mutations in this region abolished these interactions. The
association of BRCA1 with CtIP was also abrogated in cells treated with DNA
damaging agents including UV, gamma-irradiation, and adriamycin, a response
correlated with BRCA1 phosphorylation. The transactivation of the p21 promoter by
BRCA1 was diminished by expression of exogenous CtIP and CtBP. These results
suggest that the binding of the BRCT repeats of BRCA1 to CtIP/CtBP is critical in
mediating transcriptional regulation of p21 in response to DNA damage.
PMID- 10196225
TI - Regions of Byr4, a regulator of septation in fission yeast, that bind Spg1 or
Cdc16 and form a two-component GTPase-activating protein with Cdc16.
AB - In the fission yeast Schizosaccharomyces pombe, septation and constriction of the
actomyosin ring for cell division are positively regulated by the Spg1 GTPase, a
member of the Ras superfamily. Spg1 is negatively regulated by Byr4 and Cdc16,
which together form a two-component GTPase-activating protein for the Spg1
GTPase. To better understand how Byr4 regulates septation, Byr4 mutants were
tested for in vitro functions. This analysis revealed that Byr4 contained one
Cdc16-binding site and four Spg1-binding sites (SBS), designated SBS1-SBS4.
Although mutants with a single SBS bound Spg1 and inhibited GTP dissociation, the
equilibrium binding affinity of these mutants was 28-280-fold weaker than Byr4.
Because some Byr4 mutants with multiple SBSs bound Spg1 tighter than the
corresponding mutants with a single SBS, multiple SBSs probably interact to cause
the high affinity binding of Byr4 to Spg1. A region of Byr4 that bound Spg1,
SBS4, and the region that bound Cdc16, Cdc16-binding site, was necessary and
sufficient to form Cdc16-dependent Spg1GAP activity that was similar to that of
wild-type Byr4 with Cdc16.
PMID- 10196226
TI - The small heat shock-related protein, HSP20, is phosphorylated on serine 16
during cyclic nucleotide-dependent relaxation.
AB - The small heat shock-related protein 20 (HSP20) is present in four isoforms in
bovine carotid artery smooth muscles. Three of the isoforms are phosphorylated
and one is not. Increases in the phosphorylation of two isoforms of HSP20
(isoform 3, pI 5.9; and 8, pI 5.7) are associated with cyclic nucleotide
dependent relaxation of bovine carotid artery smooth muscles. Increases in the
phosphorylation of another isoform (isoform 4, pI 6.0) are associated with
phorbol ester-induced contraction of bovine carotid artery smooth muscles. In
this investigation we determined that isoforms 3 and 8 are phosphorylated on
Ser16 of the HSP20 molecule during activation of cAMP-dependent signaling
pathways. Phosphorylation state-specific antibodies produced against a peptide
containing phosphorylated Ser16 recognized isoforms 3 and 8 but not isoform 4. In
human vascular tissue, only isoform 3 is present. Incubation of transiently
permeabilized strips of bovine carotid artery smooth muscle with synthetic
peptides in which Ser16 is phosphorylated, inhibits contractile responses to high
extracellular KCl and to serotonin. These data suggest that phosphorylation of
HSP20 on Ser16 modulates cAMP-dependent vasorelaxation.
PMID- 10196227
TI - Structural features of LIM kinase that control effects on the actin cytoskeleton.
AB - LIM kinase phosphorylates and inactivates the actin binding/depolymerizing factor
cofilin and induces actin cytoskeletal changes. Several unique structural
features within LIM kinase were investigated for their roles in regulation of LIM
kinase activity. Disruption of the second LIM domain or the PDZ domain or
deletion of the entire amino terminus increased activity in vivo measured as
increasing aggregation of the actin cytoskeleton. A kinase-deleted alternate
splice product was identified and characterized. This alternate splice product
and a kinase inactive mutant inhibited LIM kinase in vivo, indicating that the
amino terminus suppresses activity of the kinase domain. Mutation of threonine
508 in the activation loop to valine abolished activity whereas replacement with
2 glutamic acid residues resulted in a fully active enzyme. Dephosphorylation of
LIM kinase inhibited cofilin phosphorylation. Mutation of the basic insert in the
activation loop inhibited activity in vivo, but not in vitro. These results
indicate phosphorylation is an essential regulatory feature of LIM kinase and
indicate that threonine 508 and the adjacent basic insert sequences of the
activation loop are required for this process. A combination of structural
features are thus involved in receiving upstream signals that regulate LIM kinase
induced actin cytoskeletal reorganization.
PMID- 10196228
TI - Transforming growth factor beta1 rescues serum deprivation-induced apoptosis via
the mitogen-activated protein kinase (MAPK) pathway in macrophages.
AB - Cell death and cell survival are central components of normal development and
pathologic states. Transforming growth factor beta1 (TGF-beta1) is a pleiotropic
cytokine that regulates both cell growth and cell death. To better understand the
molecular mechanisms that control cell death or survival, we investigated the
role of TGF-beta1 in the apoptotic process by dominant-negative inhibition of
both TGF-beta1 and mitogen-activated protein kinase (MAPK) signaling pathways.
Murine macrophages (RAW 264.7) undergo apoptosis following serum deprivation, as
determined by DNA laddering assay. However, apoptosis is prevented in serum
deprived macrophages by the presence of exogenous TGF-beta1. Using stably
transfected RAW 264.7 cells with the kinase-deleted dominant-negative mutant of
TbetaR-II (TbetaR-IIM) cDNA, we demonstrate that this protective effect by TGF
beta1 is completely abrogated. To determine the downstream signaling pathways, we
examined TGF-beta1 effects on the MAPK pathway. We show that TGF-beta1 induces
the extracellular signal-regulated kinase (ERK) activity in a time-dependent
manner up to 4 h after stimulation. Furthermore, TGF-beta1 does not rescue serum
deprivation-induced apoptosis in RAW 264.7 cells transfected with a dominant
negative mutant MAPK (ERK2) cDNA or in wild type RAW 264.7 cells in the presence
of the MAPK kinase (MEK1) inhibitor. Taken together, our data demonstrate for the
first time that TGF-beta1 is an inhibitor of apoptosis in cultured macrophages
and may serve as a cell survival factor via TbetaR-II-mediated signaling and
downstream intracellular MAPK signaling pathway.
PMID- 10196229
TI - A TATA element is required for tRNA promoter activity and confers TATA-binding
protein responsiveness in Drosophila Schneider-2 cells.
AB - In contrast to yeast and mammalian systems, which depend principally on internal
promoter elements for tRNA gene transcription, insect systems require additional
upstream sequences. To understand the function of the upstream sequences, we have
asked whether the Bombyx mori tRNACAla and tRNASGAla genes, which are absolutely
dependent on these sequences in vitro, also require them for transcription in
vivo. We introduced wild-type and mutant versions of the Bombyx tRNAAla genes
into Drosophila Schneider-2 cells and found that the tRNACAla gene is efficiently
transcribed and that its transcription depends strongly on the distal segment of
its upstream promoter. In contrast, the tRNASGAla gene is inefficiently
transcribed, and this inefficiency results from lack of a specific sequence
within the distal tRNACAla upstream promoter. This sequence, 5'-TTTATAT-3', is
sufficient to increase the activity of the tRNASGAla promoter to that of the
tRNACAla promoter. Moreover, promoters containing the 5'-TTTATAT-3' element are
stimulated by increased levels of cellular TATA-binding protein. Together these
results indicate that, in insect cells, a TATA-like element is specifically
required to form functional TATA-binding protein-containing complexes that
promote efficient transcription of tRNA genes.
PMID- 10196230
TI - Identification by differential display of a hypertonicity-inducible inward
rectifier potassium channel highly expressed in chloride cells.
AB - By using differential mRNA display to monitor the molecular alterations
associated with adaptation of euryhaline eels to different salinities, we
identified a cDNA fragment strongly induced in seawater eel gills. Cloning of a
full-length cDNA and its expression in COS-7 cells indicated that the clone codes
for an inward rectifier K+ channel (eKir) of 372 amino acid residues, which has
two transmembrane segments and a typical pore-forming region (H5). Only low
sequence similarities are present, except the H5 region, compared with other
members of the inward rectifier K+ channel family (Kir). Consistent with this
divergence in the amino acid sequence, a phylogenetic analysis indicated early
divergence and independent evolution of eKir from other members; it is only
distantly related to the Kir5.0 subfamily members. RNase protection analysis
showed that eKir is highly expressed in the seawater eel gill, kidney, and
posterior intestine but very weakly in freshwater eels. Immunohistochemistry of
gill sections revealed dense localization of eKir in the chloride cells.
Immunoelectron microscopy indicated that eKir is mainly present in the
microtubular system in the chloride cell. This location and its salt-inducible
nature suggest that the eKir channel cloned here is a novel member of the Kir5.0
subfamily of the Kir family and is implicated in osmoregulation.
PMID- 10196231
TI - The structure of an electron transfer complex containing a cytochrome c and a
peroxidase.
AB - Efficient biological electron transfer may require a fluid association of redox
partners. Two noncrystallographic methods (a new molecular docking program and 1H
NMR spectroscopy) have been used to study the electron transfer complex formed
between the cytochrome c peroxidase (CCP) of Paracoccus denitrificans and
cytochromes c. For the natural redox partner, cytochrome c550, the results are
consistent with a complex in which the heme of a single cytochrome lies above the
exposed electron-transferring heme of the peroxidase. In contrast, two molecules
of the nonphysiological but kinetically competent horse cytochrome bind between
the two hemes of the peroxidase. These dramatically different patterns are
consistent with a redox active surface on the peroxidase that may accommodate
more than one cytochrome and allow lateral mobility.
PMID- 10196232
TI - Posttranslational removal of the carboxyl-terminal KDEL of the cysteine protease
SH-EP occurs prior to maturation of the enzyme.
AB - SH-EP is a cysteine protease from germinating mung bean (Vigna mungo) that
possesses a carboxyl-terminal endoplasmic reticulum (ER) retention sequence,
KDEL. In order to examine the function of the ER retention sequence, we expressed
a full-length cDNA of SH-EP and a minus-KDEL control in insect Sf-9 cells using
the baculovirus system. Our observations on the synthesis, processing, and
trafficking of SH-EP in Sf-9 cells suggest that the KDEL ER-retention sequence is
posttranslationally removed either while the protein is still in the ER or
immediately after its exit from the ER, resulting in the accumulation of proSH-EP
minus its KDEL signal. It is this intermediate form that appears to progress
through the endomembrane system and is subsequently processed to form mature
active SH-EP. The removal of an ER retention may regulate protein delivery to a
functional site and present an alternative role for ER retention sequences in
addition to their well established role in maintaining the protein composition of
the ER lumen.
PMID- 10196233
TI - A silencer element in the regulatory region of glutamine synthetase controls cell
type-specific repression of gene induction by glucocorticoids.
AB - Glutamine synthetase is a key enzyme in the recycling of the neurotransmitter
glutamate. Expression of this enzyme is regulated by glucocorticoids, which
induce a high level of glutamine synthetase in neural but not in various non
neural tissues. This is despite the fact that non-neural cells express functional
glucocorticoid receptor molecules capable of inducing other target genes.
Sequencing and functional analysis of the upstream region of the glutamine
synthetase gene identified, 5' to the glucocorticoid response element (GRE), a 21
base pair glutamine synthetase silencer element (GSSE), which showed considerable
homology with the neural restrictive silencer element NRSE. The GSSE was able to
markedly repress the induction of gene transcription by glucocorticoids in non
neural cells and in embryonic neural retina. The repressive activity of the GSSE
could be conferred on a heterologous GRE promoter and was orientation- and
position-independent with respect to the transcriptional start site, but appeared
to depend on a location proximal to the GRE. Gel-shift assays revealed that non
neural cells and cells of early embryonic retina contain a high level of GSSE
binding activity and that this level declines progressively with age. Our results
suggest that the GSSE might be involved in the restriction of glutamine
synthetase induction by glucocorticoids to differentiated neural tissues.
PMID- 10196234
TI - Pro-adhesive and chemotactic activities of thrombospondin-1 for breast carcinoma
cells are mediated by alpha3beta1 integrin and regulated by insulin-like growth
factor-1 and CD98.
AB - Thrombospondin-1 (TSP1) is a matricellular protein that displays both pro- and
anti-adhesive activities. Binding to sulfated glycoconjugates mediates most high
affinity binding of soluble TSP1 to MDA-MB-435 cells, but attachment and
spreading of these cells on immobilized TSP1 is primarily beta1 integrin
dependent. The integrin alpha3beta1 is the major mediator of breast carcinoma
cell adhesion and chemotaxis to TSP1. This integrin is partially active in MDA-MB
435 cells but is mostly inactive in MDA-MB-231 and MCF-7 cells, which require
beta1 integrin activation to induce spreading on TSP1. Integrin-mediated cell
spreading on TSP1 is accompanied by extension of filopodia containing beta1
integrins. TSP1 binding activity of the alpha3beta1 integrin is not stimulated by
CD47-binding peptides from TSP1 or by protein kinase C activation, which activate
alphavbeta3 integrin function in the same cells. In MDA-MB-231 but not MDA-MB-435
cells, this integrin is activated by pertussis toxin, whereas serum, insulin,
insulin-like growth factor-1, and ligation of CD98 increase activity of this
integrin in both cell lines. Serum stimulation is accompanied by increased
surface expression of CD98, whereas insulin-like growth factor-1 does not
increase CD98 expression. Thus, the pro-adhesive activity of TSP1 for breast
carcinoma cells is controlled by several signals that regulate activity of the
alpha3beta1 integrin.
PMID- 10196235
TI - Enhancement of cell adhesion and spreading by a cartilage-specific noncollagenous
protein, cartilage matrix protein (CMP/Matrilin-1), via integrin alpha1beta1.
AB - Cartilage matrix protein (CMP; also known as matrilin-1), one of the major
noncollagenous proteins in most cartilages, binds to aggrecan and type II
collagen. We examined the effect of CMP on the adhesion of chondrocytes and
fibroblasts using CMP-coated dishes. The CMP coating at 10-20 micrograms/ml
enhanced the adhesion and spreading of rabbit growth plate, resting and articular
chondrocytes, and fibroblasts and human epiphyseal chondrocytes and MRC5
fibroblasts. The effect of CMP on the spreading of chondrocytes was
synergistically increased by native, but not heated, type II collagen (gelatin).
The monoclonal antibody to integrin alpha1 or beta1 abolished CMP-induced cell
adhesion and spreading, whereas the antibody to integrin alpha2, alpha3, alpha5,
beta2, alpha5beta1, or alphaVbeta5 had little effect on cell adhesion or
spreading. The antibody to integrin alpha1, but not to other subunits,
coprecipitated 125I-CMP that was added to MRC5 cell lysates, indicating the
association of CMP with the integrin alpha1 subunit. Unlabeled CMP competed for
the binding to integrin alpha1 with 125I-CMP. These findings suggest that CMP is
a potent adhesion factor for chondrocytes, particularly in the presence of type
II collagen, and that integrin alpha1beta1 is involved in CMP-mediated cell
adhesion and spreading. Since CMP is expressed almost exclusively in cartilage,
this adhesion factor, unlike fibronectin or laminin, may play a special role in
the development and remodeling of cartilage.
PMID- 10196236
TI - Age-dependent decline in mitogenic stimulation of hepatocytes. Reduced
association between Shc and the epidermal growth factor receptor is coupled to
decreased activation of Raf and extracellular signal-regulated kinases.
AB - The proliferative potential of the liver has been well documented to decline with
age. However, the molecular mechanism of this phenomenon is not well understood.
Cellular proliferation is the result of growth factor-receptor binding and
activation of cellular signaling pathways to regulate specific gene
transcription. To determine the mechanism of the age-related difference in
proliferation, we evaluated extracellular signal-regulated kinase-mitogen
activated protein kinase activation and events upstream in the signaling pathway
in epidermal growth factor (EGF)-stimulated hepatocytes isolated from young and
old rats. We confirm the age-associated decrease in extracellular signal
regulated kinase-mitogen-activated protein kinase activation in response to EGF
that has been previously reported. We also find that the activity of the upstream
kinase, Raf kinase, is decreased in hepatocytes from old compared with young
rats. An early age-related difference in the EGF-stimulated pathway is shown to
be the decreased ability of the adapter protein, Shc, to associate with the EGF
receptor through the Shc phosphotyrosine binding domain. To address the mechanism
of decreased Shc/EGF receptor interaction, we examined the phosphorylation of the
EGF receptor at tyrosine 1173, a site recognized by the Shc phosphotyrosine
binding domain. Tyrosine 1173 of the EGF receptor is underphosphorylated in the
hepatocytes from old animals compared with young in a Western blot analysis using
a phosphospecific antibody that recognizes phosphotyrosine 1173 of the EGF
receptor. These data suggest that a molecular mechanism underlying the age
associated decrease in hepatocyte proliferation involves an age-dependent
regulation of site-specific tyrosine residue phosphorylation on the EGF receptor.
PMID- 10196237
TI - The proteoglycan lectin domain binds sulfated cell surface glycolipids and
promotes cell adhesion.
AB - The lecticans are a group of chondroitin sulfate proteoglycans characterized by
the presence of C-type lectin domains. Despite the suggestion that their lectin
domains interact with carbohydrate ligands, the identity of such ligands has not
been elucidated. We previously showed that brevican, a nervous system-specific
lectican, binds the surface of B28 glial cells (Yamada, H., Fredette, B.,
Shitara, K., Hagihara, K., Miura, R., Ranscht, B., Stallcup, W. B., and
Yamaguchi, Y. (1997) J. Neurosci. 17, 7784-7795). In this paper, we demonstrate
that two classes of sulfated glycolipids, sulfatides and HNK-1-reactive
sulfoglucuronylglycolipids (SGGLs), act as cell surface receptors for brevican.
The lectin domain of brevican binds sulfatides and SGGLs in a calcium-dependent
manner as expected of a C-type lectin domain. Intact, full-length brevican also
binds both sulfatides and SGGLs. The lectin domain immobilized as a substrate
supports adhesion of cells expressing SGGLs or sulfatides, which was inhibited by
monoclonal antibodies against these glycolipids or by treatment of the substrate
with SGGLs or sulfatides. Our findings demonstrate that the interaction between
the lectin domains of lecticans and sulfated glycolipids comprises a novel cell
substrate recognition system, and suggest that lecticans in extracellular
matrices serve as substrate for adhesion and migration of cells expressing these
glycolipids in vivo.
PMID- 10196238
TI - Trafficking of the Igalpha/Igbeta heterodimer with membrane Ig and bound antigen
to the major histocompatibility complex class II peptide-loading compartment.
AB - The binding of antigen to the B cell antigen receptor (BCR) initiates two major
cellular events. First, upon cross-linking by antigen, the BCR induces signal
transduction cascades leading to the transcription of a number of genes
associated with B cell activation. Second, the BCR internalizes and delivers
antigens to processing compartments, where processed antigenic peptides are
loaded onto major histocompatibility complex (MHC) class II molecules for
presentation to T helper cells. The BCR consists of membrane Ig (mIg) and
Igalpha/Igbeta heterodimer (Igalpha/Igbeta). The Igalpha/Igbeta, the signal
transducing component of the BCR, has been indicated to play a role in antigen
processing. In order to understand the function of the Igalpha/Igbeta in antigen
transport, we studied the intracellular trafficking pathway of the
Igalpha/Igbeta. We show that in the absence of antigen binding, the
Igalpha/Igbeta constitutively traffics with mIg from the plasma membrane, through
the early endosomes, to the MHC class II peptide-loading compartment. Cross
linking the BCR does not alter the trafficking pathway; however, it accelerates
the transport of the Igalpha/Igbeta to the MHC class II peptide-loading
compartment. This suggests that the Igalpha/Igbeta heterodimer is involved in BCR
mediated antigen transport through the entire antigen transport pathway.
PMID- 10196240
TI - When two is better than one: thoughts on three decades of interaction between
Virology and the Journal of Virology.
PMID- 10196241
TI - Role of rubella virus glycoprotein domains in assembly of virus-like particles.
AB - Rubella virus is a small enveloped positive-strand RNA virus that assembles on
intracellular membranes in a variety of cell types. The virus structural proteins
contain all of the information necessary to mediate the assembly of virus-like
particles in the Golgi complex. We have recently identified intracellular
retention signals within the two viral envelope glycoproteins. E2 contains a
Golgi retention signal in its transmembrane domain, whereas a signal for
retention in the endoplasmic reticulum has been localized to the transmembrane
and cytoplasmic domains of E1 (T. C. Hobman, L. Woodward, and M. G. Farquhar,
Mol. Biol. Cell 6:7-20, 1995; T. C. Hobman, H. F. Lemon, and K. Jewell, J. Virol.
71:7670-7680, 1997). In the present study, we have analyzed the role of these
retention signals in the assembly of rubella virus-like particles. Deletion or
replacement of these domains with analogous regions from other type I membrane
glycoproteins resulted in failure of rubella virus-like particles to be secreted
from transfected cells. The E1 transmembrane and cytoplasmic domains were not
required for targeting of the structural proteins to the Golgi complex and,
surprisingly, assembly and budding of virus particles into the lumen of this
organelle; however, the resultant particles were not secreted. In contrast,
replacement or alteration of the E2 transmembrane or cytoplasmic domain,
respectively, abrogated the targeting of the structural proteins to the budding
site, and consequently, no virion formation was observed. These results indicate
that the transmembrane and cytoplasmic domains of E2 and E1 are required for
early and late steps respectively in the viral assembly pathway and that rubella
virus morphogenesis is very different from that of the structurally similar
alphaviruses.
PMID- 10196242
TI - Regulation of vaccinia virus morphogenesis: phosphorylation of the A14L and A17L
membrane proteins and C-terminal truncation of the A17L protein are dependent on
the F10L kinase.
AB - This study focused on three vaccinia virus-encoded proteins that participate in
early steps of virion morphogenesis: the A17L and A14L membrane proteins and the
F10L protein kinase. We found that (i) the A17L protein was cleaved at or near an
AGX consensus motif at amino acid 185, thereby removing its acidic C terminus;
(ii) the nontruncated form was associated with immature virions, but only the C
terminal truncated protein was present in mature virions; (iii) the nontruncated
form of the A17L protein was phosphorylated on serine, threonine, and tyrosine
residues, whereas the truncated form was unphosphorylated; (iv) nontruncated and
truncated forms of the A17L protein existed in a complex with the A14L membrane
protein; (v) C-terminal cleavage of the A17L protein and phosphorylation of the
A17L and A14L proteins failed to occur in cells infected with a F10L kinase
mutant at the nonpermissive temperature; and (vi) the F10L kinase was the only
viral late protein that was necessary for phosphorylation of the A17L protein,
whereas additional proteins were needed for C-terminal cleavage. We suggest that
phosphorylation of the A17L and A14L proteins is mediated by the F10L kinase and
is required to form the membranes associated with immature virions. Removal of
phosphates and the A17L acidic C-terminal peptide occur during the transition to
mature virions.
PMID- 10196243
TI - Highly potent RANTES analogues either prevent CCR5-using human immunodeficiency
virus type 1 infection in vivo or rapidly select for CXCR4-using variants.
AB - The natural ligands for the CCR5 chemokine receptor, macrophage inflammatory
protein 1alpha (MIP-1alpha), MIP-1beta, and RANTES (regulated on T-cell
activation, normal T-cell expressed and secreted), are known to inhibit human
immunodeficiency virus (HIV) entry, and N-terminally modified RANTES analogues
are more potent than native RANTES in blocking infection. However, potent CCR5
blocking agents may select for HIV-1 variants that use alternative coreceptors at
less than fully inhibitory concentrations. In this study, two N-terminal chemical
modifications of RANTES produced by total synthesis, aminooxypentane (AOP)
RANTES[2-68] and N-nonanoyl (NNY)-RANTES[2-68], were tested for their ability to
prevent HIV-1 infection and to select for coreceptor switch variants in the human
peripheral blood lymphocyte-SCID mouse model. Mice were infected with a CCR5
using HIV-1 isolate that requires only one or two amino acid substitutions to use
CXCR4 as a coreceptor. Even though it achieved lower circulating concentrations
than AOP-RANTES (75 to 96 pM as opposed to 460 pM under our experimental
conditions), NNY-RANTES was more effective in preventing HIV-1 infection.
However, in a subset of treated mice, these levels of NNY-RANTES rapidly selected
viruses with mutations in the V3 loop of envelope that altered coreceptor usage.
These results reinforce the case for using agents that block all significant HIV
1 coreceptors for effective therapy.
PMID- 10196244
TI - Evolution and biological characterization of human immunodeficiency virus type 1
subtype E gp120 V3 sequences following horizontal and vertical virus transmission
in a single family.
AB - It has been suggested that immune-pressure-mediated positive selection operates
to maintain the antigenic polymorphism on the third variable (V3) loop of the
gp120 of human immunodeficiency virus type 1 (HIV-1). Here we present evidence,
on the basis of sequencing 147 independently cloned env C2/V3 segments from a
single family (father, mother, and their child), that the intensity of positive
selection is related to the V3 lineage. Phylogenetic analysis and amino acid
comparison of env C2/V3 and gag p17/24 regions indicated that a single HIV-1
subtype E source had infected the family. The analyses of unique env C2/V3 clones
revealed that two V3 lineage groups had evolved in the parents. Group 1 was
maintained with low variation in all three family members regardless of the
clinical state or the length of infection, whereas group 2 was only present in
symptomatic individuals and was more positively charged and diverse than group 1.
Only virus isolates carrying the group 2 V3 sequences infected and induced
syncytia in MT2 cells, a transformed CD4(+)-T-cell line. A statistically
significant excess of nonsynonymous substitutions versus synonymous substitutions
was demonstrated only for the group 2 V3 region. The data suggest that HIV-1
variants, possessing the more homogeneous group 1 V3 element and exhibiting the
non-syncytium-inducing phenotype, persist in infected individuals independent of
clinical status and appear to be more resistant to positive selection pressure.
PMID- 10196245
TI - Enhanced measles virus cDNA rescue and gene expression after heat shock.
AB - Rescue of negative-stranded RNA viruses from full-length genomic cDNA clones is
an essential technology for genetic analysis of this class of viruses. Using this
technology in our studies of measles virus (MV), we found that the efficiency of
the measles virus rescue procedure (F. Radecke et al., EMBO J. 14:5773-5784,
1995) could be improved by modifying the procedure in two ways. First, we found
that coculture of transfected 293-3-46 cells with a monolayer of Vero cells
increased the number of virus-producing cultures about 20-fold. Second, we
determined that heat shock treatment increased the average number of transfected
cultures that produced virus another two- to threefold. In addition, heat shock
increased the number of plaques produced by positive cultures. The effect of heat
shock on rescue led us to test the effect on transient expression from an MV
minireplicon. Heat shock increased the level of reporter gene expression when
either minireplicon DNA or RNA was used regardless of whether complementation was
provided by cotransfection with expression plasmids or infection with MV helper
virus. In addition, we found that MV minireplicon gene expression could be
stimulated by cotransfection with an Hsp72 expression plasmid, indicating that
hsp72 likely plays a role in the effect of heat shock.
PMID- 10196246
TI - Phylogenetic analysis of H7 avian influenza viruses isolated from the live bird
markets of the Northeast United States.
AB - The presence of low-pathogenic H7 avian influenza virus (AIV), which is
associated with live-bird markets (LBM) in the Northeast United States, was first
detected in 1994 and, despite efforts to eradicate the virus, surveillance of
these markets has resulted in numerous isolations of H7 AIVs from several states
from 1994 through 1998. The hemagglutinin, nonstructural, and matrix genes from
representative H7 isolates from the LBM and elsewhere were sequenced, and the
sequences were compared phylogenetically. The hemagglutinin gene of most LBM
isolates examined appeared to have been the result of a single introduction of
the hemagglutinin gene. Evidence for evolutionary changes were observed with
three definable steps. The first isolate from 1994 had the amino acid threonine
at the -2 position of the hemagglutinin cleavage site, which is the most commonly
observed amino acid at this site for North American H7 AIVs. In January 1995 a
new genotype with a proline at the -2 position was detected, and this genotype
eventually became the predominant virus isolate. A third viral genotype, detected
in November 1996, had an eight-amino-acid deletion within the putative receptor
binding site. This viral genotype appeared to be the predominant isolate,
although isolates with proline at the -2 position without the deletion were still
observed in viruses from the last sampling date. Evidence for reassortment of
multiple viral genes was evident. The combination of possible adaptive evolution
of the virus and reassortment with different influenza virus genes makes it
difficult to determine the risk of pathogenesis of this group of H7 AIVs.
PMID- 10196247
TI - Characterization of an E1A-CBP interaction defines a novel transcriptional
adapter motif (TRAM) in CBP/p300.
AB - The adenovirus E1A protein subverts cellular processes to induce mitotic activity
in quiescent cells. Important targets of E1A include members of the
transcriptional adapter family containing CBP/p300. Competition for CBP/p300
binding by various cellular transcription factors has been suggested as a means
of integrating different signalling pathways and may also represent a potential
mechanism by which E1A manipulates cell fate. Here we describe the
characterization of the interaction between E1A and the C/H3 region of CBP. We
define a novel conserved 12-residue transcriptional adapter motif (TRAM) within
CBP/p300 that represents the binding site for both E1A and numerous cellular
transcription factors. We also identify a sequence (FPESLIL) within adenovirus
E1A that is required to bind the CBP TRAM. Furthermore, an E1A peptide containing
the FPESLIL sequence is capable of preventing the interaction between CBP and
TRAM-binding transcription factors, such as p53, E2F, and TFIIB, thus providing a
molecular model for E1A action. As an in vivo demonstration of this model, we
used a small region of CBP containing a functional TRAM that can bind to the p53
protein. The CBP TRAM binds p53 sequences targeted by the cellular regulator
MDM2, and we demonstrate that an MDM2-p53 interaction can be disrupted by the CBP
TRAM, leading to stabilization of cellular p53 levels and the activation of p53
dependent transcription. Transcriptional activation of p53 by the CBP TRAM is
abolished by wild-type E1A but not by a CBP-binding-deficient E1A mutant.
PMID- 10196248
TI - Identification of a novel GC-rich 113-nucleotide region to complete the circular,
single-stranded DNA genome of TT virus, the first human circovirus.
AB - The sequence data (H. Okamoto et al., Hepatol. Res. 10:1-16, 1998) of a newly
discovered single-stranded DNA virus, TT virus (TTV), showed that it did not have
the terminal structure typical of a parvovirus. Elucidation of the complete
genome structure was necessary to understand the nature of TTV. We obtained a 1.0
kb amplified product from serum samples of four TTV carriers by an inverted,
nested long PCR targeted for nucleotides (nt) 3025 to 3739 and 1 to 216 of TTV.
The sequence of a clone obtained from serum sample TA278 was compared with those
registered in GenBank. The complete circular TTV genome contained a novel
sequence of 113 nt (nt 3740 to 3852 [=0]) in between the known 3'- and 5'-end
arms, forming a 117-nt GC-rich stretch (GC content, 90.6% at nt 3736 to 3852). We
found a 36-nt stretch (nt 3816 to 3851) with an 80.6% similarity to chicken
anemia virus (CAV) (nt 2237 to 2272 of M55918), a vertebrate circovirus. A
putative SP-1 site was located at nt 3834 to 3839, followed by a TATA box at nt
85 to 90, the first initiation codon of a putative VP2 at nt 107 to 109, the
termination codon of a putative VP1 at nt 2899 to 2901, and a poly(A) signal at
nt 3073 to 3078. The arrangement was similar to that of CAV. Furthermore, several
AP-2 and ATF/CREB binding sites and an NF-kappaB site were arranged around the GC
rich region in both TTV and CAV. The data suggested that TTV is circular and
similar to CAV in its genomic organization, implying that TTV is the first human
circovirus.
PMID- 10196249
TI - Cleavage of RasGAP and phosphorylation of mitogen-activated protein kinase in the
course of coxsackievirus B3 replication.
AB - Recently, we reported on tyrosine phosphorylation of distinct cellular proteins
in the course of enterovirus infections (M. Huber, H.-C. Selinka, and R. Kandolf,
J. Virol. 71:595-600, 1997). These phosphorylation events were mediated by Src
like kinases and were shown to be necessary for effective virus replication. That
study is now extended by examination of the interaction of the adapter protein
Sam68, a cellular target of Src-like kinases which has been shown to interact
with the poliovirus 3D polypeptide, with cellular signaling proteins as well as
the function of the latter during infection. Here, we report that the RNA-binding
and protein-binding protein Sam68 associates with the p21(ras) GTPase-activating
protein RasGAP. Remarkably, RasGAP is cleaved during infections with different
strains of coxsackievirus B3 as well as with echovirus 11 and echovirus 12,
yielding a 104-kDa protein fragment. This cleavage event, which cannot be
prevented by the general caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp
fluoromethylketone, may promote the activation of the Ras pathway, as shown by
the activating dual phosphorylation of the mitogen-activated protein kinases Erk
1 and Erk-2 in the late phase of infection. Moreover, downstream targets of the
mitogen-activated protein kinases, i.e., the p21(ras) exchange factor Sos-1 and
cytoplasmic phospholipase A2, are phosphorylated with parallel time courses
during infection. Activation or inhibition of cellular signaling pathways may
play a general role in regulating effective enterovirus replication and
pathogenesis, and the results of this study begin to unravel the molecular cross
talk between enterovirus infection and key cellular signaling networks.
PMID- 10196250
TI - Retroviral insertions in Evi12, a novel common virus integration site upstream of
Tra1/Grp94, frequently coincide with insertions in the gene encoding the
peripheral cannabinoid receptor Cnr2.
AB - The common virus integration site (VIS) Evi11 was recently identified within the
gene encoding the hematopoietic G-protein-coupled peripheral cannabinoid receptor
Cnr2 (also referred to as Cb2). Here we show that Cnr2 is a frequent target (12%)
for insertion of Cas-Br-M murine leukemia virus (MuLV) in primary tumors in
NIH/Swiss mice. Multiple provirus insertions in Evi11 were cloned and shown to be
located within the 3' untranslated region of the candidate proto-oncogene Cnr2.
These results suggest that proviral insertion in the Cnr2 gene is an important
step in Cas-Br-M MuLV-induced leukemogenesis in NIH/Swiss mice. To isolate
Evi11/Cnr2 collaborating proto-oncogenes, we searched for novel common VISs in
the Cas-Br-M MuLV-induced primary tumors and identified a novel frequent common
VIS, Evi12 (14%). Interestingly, 54% of the Evi11/Cnr2-rearranged primary tumors
contained insertions in Evi12 as well, which suggests cooperative action of the
target genes in these two common VISs in leukemogenesis. By interspecific
backcross analysis it was shown that Evi12 resides on mouse chromosome 10 in a
region that shares homology with human chromosomes 12q and 19p. Sequence analysis
demonstrated that Evi12 is located upstream of the gene encoding the molecular
chaperone Tra1/Grp94, which was previously mapped to mouse chromosome 10 and
human chromosome 12q22-24. Thus, Tra1/Grp94 is a candidate target gene for
retroviral activation or inactivation in Evi12. However, Northern and Western
blot analyses did not provide evidence that proviral insertion had altered the
expression of Tra1/Grp94. Additional studies are required to determine whether
Tra1/Grp94 or another candidate proto-oncogene in Evi12 is involved in
leukemogenesis.
PMID- 10196251
TI - Human follicular dendritic cells remain uninfected and capture human
immunodeficiency virus type 1 through CD54-CD11a interaction.
AB - It has been reported that human immunodeficiency virus type 1 (HIV-1) bound to
follicular dendritic cells (FDCs) remains highly infectious to CD4(+) T cells
even when it forms immune complexes with neutralizing antibody (HIV-1/IC). To
elucidate the role of FDCs in HIV-1 transmission to CD4(+) T cells in lymph
nodes, we have isolated and purified FDCs from human tonsils and examined whether
the HIV-1/IC trapped on their surface is infectious to CD4(+) T cells. To our
surprise, not the HIV-1/IC but the antibody-free HIV-1 on FDCs could be
transmitted to CD4(+) T cells. Furthermore, in contrast to previous studies
showing that FDCs are productively infected with HIV-1, the present study clearly
demonstrated that FDCs were not the target cells for HIV-1 infection. FDCs could
capture the viral particles on their surface; however, the binding of HIV-1 to
FDCs was strongly inhibited by the presence of anti-CD54 (ICAM-1) monoclonal
antibody (MAb) and anti-CD11a (LFA-1) MAb, suggesting that the adhesion molecules
play an important role in the interaction between HIV-1 and FDCs.
PMID- 10196252
TI - Opposite effects of SDF-1 on human immunodeficiency virus type 1 replication.
AB - The alpha-chemokine SDF-1 binds CXCR4, a coreceptor for human immunodeficiency
virus type 1 (HIV-1), and inhibits viral entry mediated by this receptor. Since
chemokines are potent chemoattractants and activators of leukocytes, we examined
whether the stimulation of HIV target cells by SDF-1 affects the replication of
virus with different tropisms. We observed that SDF-1 inhibited the entry of X4
strains and increased the infectivity of particles bearing either a CCR5-tropic
HIV-1 envelope or a vesicular stomatitis virus G envelope. In contrast to the
inhibitory effect of SDF-1 on X4 strains, which is at the level of entry, the
stimulatory effect does not involve envelope-receptor interactions or proviral
DNA synthesis. Rather, we observed an increased ability of Tat to transactivate
the HIV-1 long terminal repeat in the presence of the chemokine. Therefore, the
effects of SDF-1 on the HIV-1 life cycle can be multiple and opposite, including
both an inhibition of viral entry and a stimulation of proviral gene expression.
PMID- 10196253
TI - Enrichment of a precore-minus mutant of duck hepatitis B virus in experimental
mixed infections.
AB - A precore-deficient mutant of duck hepatitis B virus (DHBV) produced by site
directed mutagenesis was tested for its ability to compete with wild-type virus
in a mixed infection of 3-day-old ducklings. The mutation was shown to produce a
cis-acting defect, resulting in a replication rate that was about one-half that
of wild-type virus. Accordingly, wild-type virus was rapidly selected during the
spread of infection. During the chronic phase of the infection, however, two
selection patterns were seen. In 4 of 10 ducks, the wild-type virus slowly
replaced the precore mutant. In another four ducks, the precore mutant virus
slowly replaced the wild-type virus. In the remaining two ducklings, ratios of
wild-type and precore mutant virus fluctuated, with wild-type virus slowly
predominating. The replacement of wild-type virus was not due to the emergence of
a rapidly replicating variant of the precore mutant, since genomes cloned from
the infected ducks retained their original replication defect. Replacement of
wild-type virus, however, correlated with elevated anti-core antibody titers,
which continued to increase with time. The selection of a precore-negative strain
of DHBV may be analogous to the selection for precore mutants of HBV during
chronic hepatitis in humans.
PMID- 10196254
TI - Bystander target cell lysis and cytokine production by dengue virus-specific
human CD4(+) cytotoxic T-lymphocyte clones.
AB - Dengue hemorrhagic fever, the severe form of dengue virus infection, is believed
to be an immunopathological response to a secondary infection with a heterologous
serotype of dengue virus. Dengue virus capsid protein-specific CD4(+) cytotoxic T
lymphocyte (CTL) clones were shown to be capable of mediating bystander lysis of
non-antigen-presenting target cells. After activation by anti-CD3 or in the
presence of unlabeled antigen-presenting target cells, these clones could lyse
both Jurkat cells and HepG2 cells as bystander targets. Lysis of HepG2 cells
suggests a potential role for CD4(+) CTL in the liver involvement observed during
dengue virus infection. Three CD4(+) CTL clones were demonstrated to lyse
cognate, antigen-presenting target cells by a mechanism that primarily involves
perforin, while bystander lysis occurred through Fas/Fas ligand interactions. In
contrast, one clone used a Fas/Fas ligand mechanism to lyse both cognate and
bystander targets. Cytokine production by the CTL clones was also examined. In
response to stimulation with D2 antigen, CD4(+) T-cell clones produced gamma
interferon, tumor necrosis factor alpha (TNF-alpha) and TNF-beta. The data
suggest that CD4(+) CTL clones may contribute to the immunopathology observed
upon secondary dengue virus infections through direct cytolysis and/or cytokine
production.
PMID- 10196255
TI - Mutational analysis of heptad repeats in the membrane-proximal region of
Newcastle disease virus HN protein.
AB - For most paramyxoviruses, syncytium formation requires the expression of both
surface glycoproteins (HN and F) in the same cell, and evidence suggests that
fusion involves a specific interaction between the HN and F proteins (X. Hu et
al., J. Virol. 66:1528-1534, 1992). The stalk region of the Newcastle disease
virus (NDV) HN protein has been implicated in both fusion promotion and virus
specificity of that activity. The NDV F protein contains two heptad repeat motifs
which have been shown by site-directed mutagenesis to be critical for fusion (R.
Buckland et al., J. Gen. Virol. 73:1703-1707, 1992; T. Sergel-Germano et al., J.
Virol. 68:7654-7658, 1994; J. Reitter et al., J. Virol. 69:5995-6004, 1995).
Heptad repeat motifs mediate protein-protein interactions by enabling the
formation of coiled coils. Upon analysis of the stalk region of the NDV HN
protein, we identified two heptad repeats. Secondary structure analysis of these
repeats suggested the potential for these regions to form alpha helices. To
investigate the importance of this sequence motif for fusion promotion, we
mutated the hydrophobic a-position amino acids of each heptad repeat to alanine
or methionine. In addition, hydrophobic amino acids in other positions were also
changed to alanine. Every mutant protein retained levels of attachment activity
that was greater than or equal to the wild-type protein activity and bound to
conformation-specific monoclonal as well as polyclonal antisera. Neuraminidase
activity was variably affected. Every mutation, however, showed a dramatic
decrease in fusion promotion activity. The phenotypes of these mutant proteins
indicate that individual amino acids within the heptad repeat region of the stalk
domain of the HN protein are important for the fusion promotion activity of the
protein. These data are consistent with the idea that the HN protein associates
with the F protein via specific interactions between the heptad repeat regions of
both proteins.
PMID- 10196256
TI - Sequence and structural elements at the 3' terminus of bovine viral diarrhea
virus genomic RNA: functional role during RNA replication.
AB - Bovine viral diarrhea virus (BVDV), a member of the genus Pestivirus in the
family Flaviviridae, has a positive-stranded RNA genome consisting of a single
open reading frame and untranslated regions (UTRs) at the 5' and 3' ends.
Computer modeling suggested the 3' UTR comprised single-stranded regions as well
as stem-loop structures-features that were suspected of being essentially
implicated in the viral RNA replication pathway. Employing a subgenomic BVDV RNA
(DI9c) that was shown to function as an autonomous RNA replicon (S.-E. Behrens,
C. W. Grassmann, H. J. Thiel, G. Meyers, and N. Tautz, J. Virol. 72:2364-2372,
1998) the goal of this study was to determine the RNA secondary structure of the
3' UTR by experimental means and to investigate the significance of defined RNA
motifs for the RNA replication pathway. Enzymatic and chemical structure probing
revealed mainly the conserved terminal part (termed 3'C) of the DI9c 3' UTR
containing distinctive RNA motifs, i.e., a stable stem-loop, SL I, near the RNA
3' terminus and a considerably less stable stem-loop, SL II, that forms the 5'
portion of 3'C. SL I and SL II are separated by a long single-stranded
intervening sequence, denoted SS. The 3'-terminal four C residues of the viral
RNA were confirmed to be single stranded as well. Other intramolecular
interactions, e.g., with upstream DI9c RNA sequences, were not detected under the
experimental conditions used. Mutagenesis of the DI9c RNA demonstrated that the
SL I and SS motifs do indeed play essential roles during RNA replication.
Abolition of RNA stems, which ought to maintain the overall folding of SL I, as
well as substitution of certain single-stranded nucleotides located in the SS
region or SL I loop region, gave rise to DI9c derivatives unable to replicate.
Conversely, SL I stems comprising compensatory base exchanges turned out to
support replication, but mostly to a lower degree than the original structure.
Surprisingly, replacement of a number of residues, although they were previously
defined as constituents of a highly conserved stretch of sequence of the SS
motif, had little effect on the replication ability of DI9c. In summary, these
results indicate that RNA structure as well as sequence elements harbored within
the 3'C region of the BVDV 3' UTR create a common cis-acting element of the
replication process. The data further point at possible interaction sites of host
and/or viral proteins and thus provide valuable information for future
experiments intended to identify and characterize these factors.
PMID- 10196257
TI - Transduction of human progenitor hematopoietic stem cells by human
immunodeficiency virus type 1-based vectors is cell cycle dependent.
AB - Human immunodeficiency virus (HIV) type 1 vectors are highly efficient in their
ability to transduce human progenitor hematopoietic stem cells (PHSC). Although
mitosis was not required for transduction of these cells, transduction rates were
much greater once cells had been cultured in the presence of cytokines.
Transduction rates, however, rarely exceeded 70%. We demonstrate here that there
is a distinct subpopulation that is more easily transduced by HIV vectors. These
cells were distinguished by a disproportionate population in the S/G2/M phases of
the cell cycle. By sorting them prior to transduction, we found that those cells
in either the G1 or S/G2/M fraction were more readily transduced than G0 cells.
Maintaining the cells in G0 by omitting cytokines from the medium reduced
transduction rates by up to 10-fold. Addition of cytokines to the medium
immediately after transduction did not improve the transduction efficiency as
measured by expression of the transgene. Analysis of replication intermediates
indicated that the block to transduction of G0 cells operated near the time of
initiation of reverse transcription. These results suggest that although
lentivirus vectors can transduce nondividing PHSC, transduction efficiency is
severalfold greater once the cells exit G0 and enter G1. Further characterization
of these more transducible cells and identification of the cellular factors
responsible may enhance transduction while maintaining the pluripotentiality of
the PHSC.
PMID- 10196258
TI - Shared usage of the chemokine receptor CXCR4 by primary and laboratory-adapted
strains of feline immunodeficiency virus.
AB - Strains of the feline immunodeficiency virus (FIV) presently under investigation
exhibit distinct patterns of in vitro tropism. In particular, the adaptation of
FIV for propagation in Crandell feline kidney (CrFK) cells results in the
selection of strains capable of forming syncytia with cell lines of diverse
species origin. The infection of CrFK cells by CrFK-adapted strains appears to
require the chemokine receptor CXCR4 and is inhibited by its natural ligand,
stromal cell-derived factor 1alpha (SDF-1alpha). Here we found that inhibitors of
CXCR4-mediated infection by human immunodeficiency virus type I (HIV-1), such as
the bicyclam AMD3100 and short peptides derived from the amino-terminal region of
SDF-1alpha, also blocked infection of CrFK by FIV. Nevertheless, we observed
differences in the ranking order of the peptides as inhibitors of FIV and HIV-1
and showed that such differences are related to the species origin of CXCR4 and
not that of the viral envelope. These results suggest that, although the envelope
glycoproteins of FIV and HIV-1 are substantially divergent, FIV and HIV-1
interact with CXCR4 in a highly similar manner. We have also addressed the role
of CXCR4 in the life cycle of primary isolates of FIV. Various CXCR4 ligands
inhibited infection of feline peripheral blood mononuclear cells (PBMC) by
primary FIV isolates in a concentration-dependent manner. These ligands also
blocked the viral transduction of feline PBMC by pseudotyped viral particles when
infection was mediated by the envelope glycoprotein of a primary FIV isolate but
not by the G protein of vesicular stomatitis virus, indicating that they act at
an envelope-mediated step and presumably at viral entry. These findings strongly
suggest that primary and CrFK-adapted strains of FIV, despite disparate in vitro
tropisms, share usage of CXCR4.
PMID- 10196259
TI - Genetic divergence with emergence of novel phenotypic variants of equine
arteritis virus during persistent infection of stallions.
AB - The persistently infected carrier stallion is the critical natural reservoir of
equine arteritis virus (EAV), as venereal infection of mares frequently occurs
after breeding to such stallions. Two Thoroughbred stallions that were infected
during the 1984 outbreak of equine viral arteritis in central Kentucky
subsequently became long-term EAV carriers. EAV genomes amplified from the semen
of these two stallions were compared by sequence analysis of the six 3' open
reading frames (ORFs 2 through 7), which encode the four known structural
proteins and two uncharacterized glycoproteins. The major variants of the EAV
population that sequentially arose within the reproductive tract of each carrier
stallion varied by approximately 1% per year, and the heterogeneity of the viral
quasispecies increased during the course of long-term persistent infection. The
various ORFs of the dominant EAV variants evolved independently, and there was
apparently strong selective pressure on the uncharacterized GP3 protein during
persistent infection. Amino acid changes also occurred in the V1 variable region
of the GL protein. This region has been previously identified as a crucial
neutralization domain, and selective pressures exerted on the V1 region during
persistent EAV infection led to the emergence of virus variants with distinct
neutralization properties. Thus, evolution of the EAV quasispecies that occurs
during persistent infection of the stallion clearly can influence viral
phenotypic properties such as neutralization and perhaps virulence.
PMID- 10196260
TI - Spliced mRNA encoding the murine cytomegalovirus chemokine homolog predicts a
beta chemokine of novel structure.
AB - A viral mRNA of the late kinetic class expressed by murine cytomegalovirus (MCMV)
contains an open reading frame (ORF) whose predicted protein, designated MCK-1,
has homology to beta chemokines (M. R. MacDonald, X.-Y. Li, and H. W. Virgin IV,
J. Virol. 71:1671-1678, 1997). The present study analyzed further the structure
of the transcript in infected fibroblast cells. A splicing event removed the MCK
1 stop codon, bringing a downstream ORF into frame with the chemokine homolog and
demonstrating that the MCK-1 ORF was an exon of a larger gene. The predicted 31.4
kDa protein, designated MCK-2, contains a putative amino-terminal signal sequence
and a beta chemokine domain, followed by a carboxyl-terminal domain without
significant homology to known proteins. Quantitative analysis of mRNA forms in
MCMV-infected fibroblast cells at late times after infection indicated that the
viral chemokine RNA was predominantly spliced. There was no evidence for
expression of RNA encoding either MCK-1 or MCK-2 at immediate early or early
times after infection with MCMV. Monoclonal antibodies generated against
bacterially expressed MCK-2 recognized multiple proteins in the range of
approximately 30 to approximately 45 kDa in Western blot analysis of MCK-2
expressed in transfected COS cells. The monoclonal antibodies immunoprecipitated
a similar group of proteins in transfected COS cells metabolically labeled with
radioactive cysteine. Radiolabelled protein of apparent higher molecular mass was
immunoprecipitated from culture medium overlying the transfected cells,
suggesting that posttranslationally modified MCK-2 can be secreted. Two proteins
with apparent molecular mass suggestive of posttranslational modification were
detected by Western blot analysis of cells harvested at late times after
infection with MCMV. These studies show that MCMV encodes and expresses a beta
chemokine homolog with a novel predicted structure.
PMID- 10196261
TI - High major histocompatibility complex-unrestricted lysis of simian
immunodeficiency virus envelope-expressing cells predisposes macaques to rapid
AIDS progression.
AB - Before the development of virus-specific immune responses, peripheral blood
mononuclear cells (PBMC) from uninfected rhesus monkeys and human beings have the
capacity to lyse target cells expressing simian immunodeficiency virus (SIV) or
human immunodeficiency virus-1 (HIV) envelope (gp130 and gp120) antigens. Lysis
by naive effector cells does not require major histocompatibility complex (MHC)
restricted antigen presentation, is equally effective for allogeneic and
xenogeneic targets, and is designated MHC-unrestricted (UR) lysis. UR lysis is
not sensitive to EGTA and does not require de novo RNA or protein synthesis.
Several kinds of envelope-expressing targets, including cells that poorly express
MHC class I antigens, can be lysed. CD4(+) effectors are responsible for most of
the lytic activity. High lysis is correlated with high expression of HIV or SIV
envelope, specifically, the central one-third of the gp130 molecule, and lysis is
completely inhibited by a monoclonal antibody against envelope. Our work extends
observations of human lymphocytes expressing HIV gp120 to the SIV/rhesus monkey
model for AIDS. Additionally, we address the relevance of UR lysis in vivo. A
survey of PBMC from 56 uninfected rhesus monkeys indicates that 59% of the
individuals had peak UR lytic activity above 15% specific lysis. Eleven of these
monkeys were subsequently infected with SIV. Animals with UR lytic activity above
15% specific lysis were predisposed to more rapid disease progression than
animals with low UR lytic activity, suggesting a strong correlation between this
form of innate immunity and disease progression to AIDS.
PMID- 10196262
TI - Prevalent class I-restricted T-cell response to the Theiler's virus epitope
Db:VP2121-130 in the absence of endogenous CD4 help, tumor necrosis factor alpha,
gamma interferon, perforin, or costimulation through CD28.
AB - C57BL/6 mice mount a cytotoxic T-lymphocyte (CTL) response against the Daniel's
strain of Theiler's murine encephalomyelitis virus (TMEV) 7 days after infection
and do not develop persistent infection or the demyelinating syndrome similar to
multiple sclerosis seen in susceptible mice. The TMEV capsid peptide VP2121-130
sensitizes H-2Db+ target cells for killing by central-nervous-system-infiltrating
lymphocytes (CNS-ILs) isolated from C57BL/6 mice infected intracranially.
Db:VP2121-130 peptide tetramers were used to stain CD8(+) CNS-ILs, revealing that
50 to 63% of these cells bear receptors specific for VP2121-130 presented in the
context of Db. No T cells bearing this specificity were found in the cervical
lymph nodes or spleens of TMEV-infected mice. H-2(b) mice lacking CD4, class II,
gamma interferon, or CD28 expression are susceptible to persistent virus
infection but surprisingly still generate high frequencies of CD8(+), Db:VP2121
130-specific T cells. However, CD4-negative mice generate a lower frequency of
Db:VP2121-130-specific T cells than do class II negative or normal H-2(b)
animals. Resistant tumor necrosis factor alpha receptor I knockout mice also
generate a high frequency of CD8(+) CNS-ILs specific for Db:VP2121-130.
Furthermore, normally susceptible FVB mice that express a Db transgene generate
Db:VP2121-130-specific CD8(+) CNS-ILs at a frequency similar to that of C57BL/6
mice. These results demonstrate that VP2121-130 presented in the context of Db is
an immunodominant epitope in TMEV infection and that the frequency of the VP2121
130-specific CTLs appears to be independent of several key inflammatory mediators
and genetic background but is regulated in part by the expression of CD4.
PMID- 10196263
TI - Altered expression of tyrosine kinases of the Src and Syk families in human T
cell leukemia virus type 1-infected T-cell lines.
AB - During the late phase of adult T-cell leukemia/lymphoma, a severe
lymphoproliferative disorder caused by human T-cell leukemia virus type 1 (HTLV
1), leukemic cells no longer produce interleukin-2. Several studies have reported
the lack of the Src-like protein tyrosine kinase Lck and overexpression of Lyn
and Fyn in these cells. In this report we demonstrate that, in addition to the
downregulation of TCR, CD45, and Lck (which are key components of T-cell
activation), HTLV-1-infected cell lines demonstrate a large increase of FynB, a
Fyn isoform usually poorly expressed in T cells. Furthermore, similar to anergic
T cells, Fyn is hyperactive in one of these HTLV-1-infected T-cell lines,
probably as a consequence of Csk downregulation. A second family of two proteins,
Zap-70 and Syk, relay the signal of T-cell activation. We demonstrate that in
contrast to uninfected T cells, Zap-70 is absent in HTLV-1-infected T cells,
whereas Syk is overexpressed. In searching for the mechanism responsible for FynB
overexpression and Zap-70 downregulation, we have investigated the ability of the
Tax and Rex proteins to modulate Zap-70 expression and the alternative splicing
mechanism which gives rise to either FynB or FynT. By using Jurkat T cells stably
transfected with the tax and rex genes or inducibly expressing the tax gene, we
found that the expression of Rex was necessary to increase fynB expression,
suggesting that Rex controls fyn gene splicing. Conversely, with the same Jurkat
clones, we found that the expression of Tax but not Rex could downregulate Zap-70
expression. These results suggest that the effect of Tax and Rex must cooperate
to deregulate the pathway of T-cell activation in HTLV-1-infected T cells.
PMID- 10196264
TI - Activation of the grp78 and grp94 promoters by hepatitis C virus E2 envelope
protein.
AB - The hepatitis C virus E1 and E2 envelope proteins are targeted to the endoplasmic
reticulum, but instead of being secreted, they are retained in a pre-Golgi
compartment, at least partly in a misfolded state. Since secretory proteins which
are retained in the endoplasmic reticulum frequently can activate the
transcription of intraluminal chaperone proteins, we measured the effect of the
E1 and E2 proteins on the promoters of two such chaperones, GRP78 (BiP) and
GRP94. We found that E2 but not E1 protein activates these two promoters, as
assayed by a reporter gene system. Furthermore, E2 but not E1 protein induces the
synthesis of GRP78 from the endogenous cellular gene. We also found that E2 but
not E1 protein expressed in mammalian cells is bound tightly to GRP78. This
association may explain the ability of E2 protein to activate transcription,
since GRP78 has been postulated to be a sensor of stress in the endoplasmic
reticulum. Since overexpression of GRP78 has been shown to decrease the
sensitivity of cells to killing by cytotoxic T lymphocytes and to increase
tumorigenicity and resistance to antitumor drugs, this activity of E2 protein may
be involved in the pathogenesis of hepatitis C virus-induced diseases.
PMID- 10196265
TI - Attenuated vesicular stomatitis viruses as vaccine vectors.
AB - We showed previously that a single intranasal vaccination of mice with a
recombinant vesicular stomatitis virus (VSV) expressing an influenza virus
hemagglutinin (HA) protein provided complete protection from lethal challenge
with influenza virus (A. Roberts, E. Kretzschmar, A. S. Perkins, J. Forman, R.
Price, L. Buonocore, Y. Kawaoka, and J. K. Rose, J. Virol. 72:4704-4711, 1998).
Because some pathogenesis was associated with the vector itself, in the present
study we generated new VSV vectors expressing HA which are completely attenuated
for pathogenesis in the mouse model. The first vector has a truncation of the
cytoplasmic domain of the VSV G protein and expresses influenza virus HA (CT1
HA). This nonpathogenic vector provides complete protection from lethal influenza
virus challenge after intranasal administration. A second vector with VSV G
deleted and expressing HA (DeltaG-HA) is also protective and nonpathogenic and
has the advantage of not inducing neutralizing antibodies to the vector itself.
PMID- 10196266
TI - Receptor-mediated interference mechanism responsible for resistance to polytropic
leukemia viruses in Mus castaneus.
AB - The Asian mouse Mus castaneus is resistant to infection by the polytropic mink
cell focus-inducing (MCF) subgroup of murine leukemia viruses (MuLVs). Genetic
crosses showed this recessive resistance to be governed by a single gene that
maps at or near the gene encoding the polytropic viral receptor, Rmc1. To
investigate this resistance, we mated M. castaneus with mice carrying the wild
mouse Sxv variant of the Rmc1 receptor that allows infection by xenotropic as
well as polytropic virus. Unlike other F1 hybrids of M. castaneus, these F1 mice
were resistant to both xenotropic and polytropic classes of MuLVs. Analysis of
backcrossed progeny of the F1 hybrids mated to Sxv mice indicates that resistance
is due to inheritance of two M. castaneus genes. Cells from individual backcross
mice were also examined for cell surface antigen by fluorescence-activated cell
sorter analysis with monoclonal antibodies reactive with xenotropic or MCF virus
env glycoproteins. A correlation was observed between virus resistance and
antigen, suggesting that virus resistance is due to expression of endogenous
viral envelope genes that interfere with infection by exogenous virus. Since the
inbred strain Rmc1 receptor remains functional in the presence of these M.
castaneus genes, and since M. castaneus contains multiple copies of xenotropic
MuLV env genes, we suggest that these resistance genes control expression of
xenotropic env glycoprotein that interferes with exogenous virus in cells
containing the Sxv variant of Rmc1.
PMID- 10196267
TI - Identification of a coronavirus hemagglutinin-esterase with a substrate
specificity different from those of influenza C virus and bovine coronavirus.
AB - We have characterized the hemagglutinin-esterase (HE) of puffinosis virus (PV), a
coronavirus closely related to mouse hepatitis virus (MHV). Analysis of the
cloned gene revealed approximately 85% sequence identity to HE proteins of MHV
and approximately 60% identity to the corresponding esterase of bovine
coronavirus. The HE protein exhibited acetylesterase activity with synthetic
substrates p-nitrophenyl acetate, alpha-naphthyl acetate, and 4
methylumbelliferyl acetate. In contrast to other viral esterases, no activity was
detectable with natural substrates containing 9-O-acetylated sialic acids.
Furthermore, PV esterase was unable to remove influenza C virus receptors from
human erythrocytes, indicating a substrate specificity different from HEs of
influenza C virus and bovine coronavirus. Solid-phase binding assays revealed
that purified PV was unable to bind to sialic acid-containing glycoconjugates
like bovine submaxillary mucin, mouse alpha1 macroglobulin or bovine brain
extract. Because of the close relationship to MHV, possible implications on the
substrate specificity of MHV esterases are suggested.
PMID- 10196268
TI - Replicative fitness of protease inhibitor-resistant mutants of human
immunodeficiency virus type 1.
AB - The relative replicative fitness of human immunodeficiency virus type 1 (HIV-1)
mutants selected by different protease inhibitors (PIs) in vivo was determined.
Each mutant was compared to wild type (WT), NL4-3, in the absence of drugs by
several methods, including clonal genotyping of cultures infected with two
competing viral variants, kinetics of viral antigen production, and viral
infectivity/virion particle ratios. A nelfinavir-selected protease D30N
substitution substantially decreased replicative capacity relative to WT, while a
saquinavir-selected L90M substitution moderately decreased fitness. The D30N
mutant virus was also outcompeted by the L90M mutant in the absence of drugs. A
major natural polymorphism of the HIV-1 protease, L63P, compensated well for the
impairment of fitness caused by L90M but only slightly improved the fitness of
D30N. Multiply substituted indinavir-selected mutants M46I/L63P/V82T/I84V and
L10R/M46I/L63P/V82T/I84V were just as fit as WT. These results indicate that the
mutations which are usually initially selected by nelfinavir and saquinavir, D30N
and L90M, respectively, impair fitness. However, additional mutations may improve
the replicative capacity of these and other drug-resistant mutants. Hypotheses
based on the greater fitness impairment of the nelfinavir-selected D30N mutant
are suggested to explain observations that prolonged responses to delayed salvage
regimens, including alternate PIs, may be relatively common after nelfinavir
failure.
PMID- 10196269
TI - Protection against establishment of retroviral persistence by vaccination with a
live attenuated virus.
AB - Many human viruses not only cause acute diseases but also establish persistent
infections. Such persistent viruses can cause chronic diseases or can reactivate
to cause acute diseases in AIDS patients or patients receiving immunosuppressive
therapies. While the prevention of persistent infections is an important
consideration in the design of modern vaccines, surprisingly little is known
about this aspect of protection. In the current study, we tested the feasibility
of vaccine prevention of retroviral persistence by using a Friend virus model
that we recently developed. In this model, persistent virus can be detected at
very low levels by immunosuppressing the host to reactivate virus or by
transferring persistently infected spleen cells into highly susceptible mice. Two
vaccines were analyzed, a recombinant vaccinia virus vector expressing Friend
virus envelope protein and a live attenuated Friend virus. Both vaccines reduced
pathogenic virus loads to levels undetectable by infectious center assays.
However, only the live, attenuated vaccine prevented immunosuppression-induced
reactivation of persistent virus. Thus, even very low levels of persistent Friend
virus posed a significant threat during immunosuppression. Our results
demonstrate that vaccine protection against establishment of retroviral
persistence is attainable.
PMID- 10196270
TI - Identification of a receptor-binding pocket on the envelope protein of friend
murine leukemia virus.
AB - Based on previous structural and functional studies, a potential receptor-binding
site composed of residues that form a pocket at one end of the two long
antiparallel helices in the receptor-binding domain of Friend 57 murine leukemia
virus envelope protein (RBD) has been proposed. To test this hypothesis, directed
substitutions for residues in the pocket were introduced and consequences for
infection and for receptor binding were measured. Receptor binding was measured
initially by a sensitive assay based on coexpression of receptor and RBD in
Xenopus oocytes, and the findings were confirmed by using purified proteins.
Three residues that are critical for both binding and infection (S84, D86, and
W102), with side chains that extend into the pocket, were identified. Moreover,
when mCAT-1 was overexpressed, the infectivity of Fr57-MLV carrying pocket
substitutions was partially restored. Substitutions for 18 adjacent residues and
11 other previously unexamined surface-exposed residues outside of the RBD pocket
had no detectable effect on function. Taken together, these findings support a
model in which the RBD pocket interacts directly with mCAT-1 (likely residues,
Y235 and E237) and multiple receptor-envelope complexes are required to form the
fusion pore.
PMID- 10196271
TI - Host-specific modulation of the selective constraints driving human
immunodeficiency virus type 1 env gene evolution.
AB - To address the evolution of human immunodeficiency virus type 1 (HIV-1) within a
single host, we analyzed the HIV-1 C2-V5 env regions of both cell-free genomic
RNA- and proviral-DNA-derived clones. Sequential samples were collected over a
period of 3 years from six untreated subjects (three typical progressors [TPs]
and three slow progressors [SPs], all with a comparable length of infection
except one. The evolutionary analysis of the C2-V5 env sequences performed on 506
molecular clones (253 RNA- and 253 DNA-derived sequences) highlighted a series of
differences between TPs and SPs. In particular, (i) clonal sequences from SPs
(DNA and RNA) showed lower nucleotide similarity than those from TPs (P = 0.
0001), (ii) DNA clones from SPs showed higher intra- and intersample nucleotide
divergence than those from TPs (P < 0.05), (iii) higher host-selective pressure
was generally detectable in SPs (DNA and RNA sequences), and (iv) the increase in
the genetic distance of DNA and RNA sequences over time was paralleled by an
increase in both synonymous (Ks) and nonsynonymous (Ka) substitutions in TPs but
only in nonsynonymous substitutions in SPs. Several individual peculiarities of
the HIV-1 evolutionary dynamics emerged when the V3, V4, and V5 env regions of
both TPs and SPs were evaluated separately. These peculiarities, probably
reflecting host-specific features of selective constraints and their continuous
modulation, are documented by the dynamics of Ka/Ks ratios of hypervariable env
domains.
PMID- 10196272
TI - Activation of caspases and p53 by bovine herpesvirus 1 infection results in
programmed cell death and efficient virus release.
AB - Programmed cell death (PCD), or apoptosis, is initiated in response to various
stimuli, including virus infection. Bovine herpesvirus 1 (BHV-1) induces PCD in
peripheral blood mononuclear cells at the G0/G1 phase of the cell cycle (E.
Hanon, S. Hoornaert, F. Dequiedt, A. Vanderplasschen, J. Lyaku, L. Willems, and
P.-P. Pastoret, Virology 232:351-358, 1997). However, penetration of virus
particles is not required for PCD (E. Hanon, G. Meyer, A. Vanderplasschen, C.
Dessy-Doize, E. Thiry, and P. P. Pastoret, J. Virol. 72:7638-7641, 1998). The
mechanism by which BHV-1 induces PCD in peripheral blood mononuclear cells is not
understood, nor is it clear whether nonlymphoid cells undergo PCD following
infection. This study demonstrates that infection of bovine kidney (MDBK) cells
with BHV-1 leads to PCD, as judged by terminal deoxynucleotidyltransferase
mediated dUTP-biotin nick end labeling, DNA laddering, and chromatin
condensation. p53 appears to be important in this process, because p53 levels and
promoter activity increased after infection. Expression of proteins that are
stimulated by p53 (p21(Waf1) and Bax) is also activated after infection. Cleavage
of Bcl-xL, a protein that inhibits PCD, occurred after infection, suggesting that
caspases (interleukin-1beta-converting enzyme-like proteases) were activated.
Other caspase substrates [poly(ADP-ribose) polymerase and actin] are also cleaved
during the late stages of infection. Inhibition of caspase activity delayed
cytotoxic activity and virus release but increased the overall virus yield. Taken
together, these results indicate that nonlymphoid cells undergo PCD near the end
of productive infection and further suggest that caspases enhance virus release.
PMID- 10196273
TI - Modulation of phosphate uptake and amphotropic murine leukemia virus entry by
posttranslational modifications of PIT-2.
AB - PIT-2 is a type III sodium phosphate cotransporter and the receptor for
amphotropic murine leukemia viruses. We have investigated the expression and the
functions of a tagged version of PIT-2 in CHO cells. PIT-2 remained equally
abundant at the cell surface within 6 h following variation of the phosphate
supply. In contrast, the efficiency of phosphate uptake and retrovirus entry was
inversely related to the extracellular phosphate concentration, indicating that
PIT-2 activities are modulated by posttranslational modifications of cell surface
molecules induced by phosphate. Conformational changes of PIT-2 contribute to
both activities, as shown by the inhibitory effect of sulfhydryl reagents known
as inhibitors of type II cotransporters. A physical association of PIT-2 with
actin was demonstrated. Modifications of the actin network were induced by
variations of the concentrations of extracellular phosphate, cytochalasin D, or
lysophosphatidic acid. They revealed that the formation of actin stress fibers
determines the cell surface distribution of PIT-2, the internalization of the
receptor in response to virus binding, and the capacity to process retrovirus
entry. Thus, the presence of PIT-2 at the cell surface is not sufficient to
ensure phosphate transport and susceptibility to amphotropic retrovirus
infection. Further activation of cell surface PIT-2 molecules is required for
these functions.
PMID- 10196274
TI - Expression and characterization of a novel structural protein of human
cytomegalovirus, pUL25.
AB - Human cytomegalovirus (HCMV) UL25 has recently been found to encode a new
structural protein that is present in both virion and defective viral particles
(C. J. Baldick and T. Shenk, J. Virol. 70:6097-6105, 1996). In the present work a
polyclonal antibody was raised against a prokaryotic pUL25 fusion protein in
order to investigate the biosynthesis and localization of the UL25 product
(pUL25) during HCMV replication in human fibroblasts. Furthermore, pUL25 was
transiently expressed in its native form and fused to the FLAG epitope, in COS7
and U373MG cells, in order to compare the properties of the isolated protein and
that produced during infection. Immunoblotting analysis revealed a group of
polypeptides, ranging from 80 to 100 kDa, in both transfected and infected cells;
in vivo labeling experiments with infected cells demonstrated they are
posttranslationally modified by phosphorylation. The transcriptional analysis of
the UL25 open reading frame combined with the study of pUL25 biosynthesis showed
true late kinetics for this protein in infected human fibroblasts. By indirect
immunofluorescence both recombinant and viral pUL25 were detected exclusively in
the cytoplasm of transfected or infected cells. Interestingly, pUL25 was shown to
localize in typical condensed structures in the perinuclear region as already
observed for other HCMV tegument proteins. Colocalization of ppUL99 in the same
vacuoles suggests that these structure are endosomal cisternae, which are
proposed to be a preferential site of viral particle envelopment. Our data
suggest that pUL25 is most likely a novel tegument protein and possibly plays a
key role in the process of envelopment.
PMID- 10196275
TI - A novel cellular protein, p60, interacting with both herpes simplex virus 1
regulatory proteins ICP22 and ICP0 is modified in a cell-type-specific manner and
Is recruited to the nucleus after infection.
AB - Herpes simplex virus 1 encodes two multifunctional regulatory proteins, infected
cell proteins 22 and 0 (ICP22 and ICP0). ICP0 is a promiscuous transactivator,
whereas ICP22 is required in vivo and for efficient replication and expression of
a subset of late (gamma2) genes in rodent or rabbit cell lines and in primary
human cell strains (restrictive cells) but not in HEp-2 or Vero (permissive)
cells. We report the identification in the yeast two-hybrid system of a cellular
protein designated p60 that interacts with ICP22. This protein (apparent Mr of
60,000) has not been previously described and has no known motifs. Analyses of
p60 revealed the following. (i) p60 bound fast-migrating, underprocessed wild
type ICP22 and ICP22 lacking the carboxyl-terminal 24 amino acids but not ICP22
lacking the carboxyl-terminal 40 amino acids, whereas the previously identified
cellular protein p78 (R. Bruni and B. Roizman, J. Virol. 72:8525-8531, 1998)
bound all forms of ICP22. The interaction of p60 with only one isoform of ICP22
supports that hypothesis that each isoform of herpes simplex virus proteins
performs a specific function that may be different from that of other isoforms.
(ii) p60 also bound ICP0; the binding of ICP0 was independent of that of ICP22.
(iii) p60 localized in uninfected rabbit skin cells in both nuclei and cytoplasm.
In rabbit skin cells infected with wild-type virus, p60 was posttranslationally
processed to a higher apparent Mr but was not redistributed. Posttranslational
processing required the presence of the genes encoding ICP22 and UL13 protein
kinase. (iv) In uninfected HEp-2 cells, p60 localized primarily in nuclei. Soon
after infection with wild-type virus, the p60 localized in discrete small nuclear
structures with ICP0. Late in infection, both ICP0 and p60 tended to disperse but
p60 did not change in apparent Mr. The localization of p60 was independent of
ICP22, but p60 tended to be more localized in small nuclear structures and less
dispersed in cells infected with mutants lacking the genes encoding the UL13 or
US3 protein kinases. The results suggest that posttranslational modification of
p60 is mediated either by ICP0 (permissive cells) or by ICP22 and UL13 protein
kinase (restrictive rabbit skin cells) and that the restrictive phenotype of
rabbit skin cells may be related to the failure to process p60 by mutants lacking
the genes encoding UL13 or ICP22.
PMID- 10196276
TI - Virus promoters determine interference by defective RNAs: selective amplification
of mini-RNA vectors and rescue from cDNA by a 3' copy-back ambisense rabies
virus.
AB - Typical defective interfering (DI) RNAs are more successful in the competition
for viral polymerase than the parental (helper) virus, which is mostly due to an
altered DI promoter composition. Rabies virus (RV) internal deletion RNAs which
possess the authentic RV terminal promoters, and which therefore are
transcriptionally active and can be used as vectors for foreign gene expression,
are poorly propagated in RV-infected cells and do not interfere with RV
replication. To allow DI-like amplification and high-level gene expression from
such mini-RNA vectors, we have used an engineered 3' copy-back (ambisense) helper
RV in which the strong replication promoter of the antigenome was replaced with
the 50-fold-weaker genome promoter. In cells coinfected with ambisense helper
virus and mini-RNAs encoding chloramphenicol acetyltransferase (CAT) and
luciferase, mini-RNAs were amplified to high levels. This was correlated with
interference with helper virus replication, finally resulting in a clear
predominance of mini-RNAs over helper virus. However, efficient successive
passaging of mini-RNAs and high-level reporter gene activity could be achieved
without adding exogenous helper virus, revealing a rather moderate degree of
interference not precluding substantial HV propagation. Compared to infections
with recombinant RV vectors expressing CAT, the availability of abundant mini-RNA
templates led to increased levels of CAT mRNA such that CAT activities were
augmented up to 250-fold, while virus gene transcription was kept to a minimum.
We have also exploited the finding that internal deletion model RNAs behave like
DI RNAs and are selectively amplified in the presence of ambisense helper virus
to demonstrate for the first time RV-supported rescue of cDNA after transfection
of mini-RNA cDNAs in ambisense RV-infected cells expressing T7 RNA polymerase.
PMID- 10196277
TI - Antiretroviral cytolytic T-lymphocyte nonresponsiveness: FasL/Fas-mediated
inhibition of CD4(+) and CD8(+) antiviral T cells by viral antigen-positive veto
cells.
AB - C57BL/6 (H-2(b)) mice generate type-specific cytolytic T-lymphocyte (CTL)
responses to an immunodominant Kb-restricted epitope, KSPWFTTL located in the
membrane-spanning domain of p15TM of AKR/Gross murine leukemia viruses (MuLV).
AKR.H-2(b) congenic mice, although carrying the responder H-2(b) major
histocompatibility complex (MHC) haplotype, are low responders or nonresponders
for AKR/Gross MuLV-specific CTL, apparently due to the presence of inhibitory
AKR. H-2(b) cells. Despite their expression of viral antigens and Kb, untreated
viable AKR.H-2(b) spleen cells cause dramatic inhibition of the C57BL/6 (B6)
antiviral CTL response to in vitro stimulation with AKR/Gross MuLV-induced tumor
cells. This inhibition is specific (AKR.H-2(b) modulator spleen cells do not
inhibit allogeneic MHC or minor histocompatibility antigen-specific CTL
production), dependent on direct contact of AKR.H-2(b) cells in a dose-dependent
manner with the responder cell population, and not due to soluble factors. Here,
the mechanism of inhibition of the antiviral CTL response is shown to depend on
Fas/Fas-ligand interactions, implying an apoptotic effect on B6 responder cells.
Although B6.gld (FasL-) responders were as sensitive to inhibition by AKR.H-2(b)
modulator cells as were B6 responders, B6.lpr (Fas-) responders were largely
insensitive to inhibition, indicating that the responder cells needed to express
Fas. A Fas-Ig fusion protein, when added to the in vitro CTL stimulation
cultures, relieved the inhibition caused by the AKR.H-2(b) cells if the primed
responders were from either B6 or B6.gld mice, indicating that the inhibitory
AKR.H-2(b) cells express FasL. Because of the antigen specificity of the
inhibition, these results collectively implicate a FasL/Fas interaction
mechanism: viral antigen-positive AKR.H-2(b) cells expressing FasL inhibit
antiviral T cells ("veto" them) when the AKR.H-2(b) cells are recognized.
Consistent with this model, inhibition by AKR.H-2(b) modulator cells was MHC
restricted, and resulted in approximately a 10- to 70-fold decrease in the in
vitro expansion of pCTL/CTL. Both CD8(+) CTL and CD4(+) Th responder cells were
susceptible to inhibition by FasL+ AKR.H-2(b) inhibitory cells as the basis for
inhibition. The CTL response in the presence of inhibitory cells could be
restored by several cytokines or agents that have been shown by others to
interfere with activation-induced cell death (e.g. , interleukin-2 [IL-2], IL-15,
transforming growth factor beta, lipopolysaccharide, 9-cis-retinoic acid) but not
others (e.g., tumor necrosis factor alpha). These results raise the possibility
that this type of inhibitory mechanism is generalized as a common strategy for
retrovirus infected cells to evade immune T-cell recognition.
PMID- 10196278
TI - Identification of a cell surface protein from Crandell feline kidney cells that
specifically binds Aleutian mink disease parvovirus.
AB - Aleutian mink disease parvovirus (ADV) is the etiological agent of Aleutian
disease of mink. The acute disease caused by ADV consists of permissive infection
of alveolar type II cells that results in interstitial pneumonitis. The
permissive infection is experimentally modeled in vitro by infecting Crandell
feline kidney (CrFK) cells with a tissue culture-adapted isolate of ADV, ADV-G.
ADV-G VP2 empty virions expressed in a recombinant baculovirus system were
analyzed for the ability to bind to the surface of CrFK cells. Radiolabeled VP2
virions bound CrFK cells specifically, while they did not bind either Mus dunni
or Spodoptera frugiperda cells, cells which are resistant to ADV infection. The
binding to CrFK cells was competitively inhibited by VP2 virions but not by
virions of cowpea chlorotic mottle virus (CCMV), another unenveloped virus
similar in size to ADV. Furthermore, preincubation of CrFK cells with the VP2
virions blocked infection by ADV-G. The VP2 virions were used in a virus overlay
protein binding assay to identify a single protein of approximately 67 kDa, named
ABP (for ADV binding protein), that demonstrates specific binding of VP2 virions.
Exogenously added VP2 virions were able to competitively inhibit the binding of
labeled VP2 virions to ABP, while CCMV virions had no effect. Polyclonal
antibodies raised against ABP reacted with ABP on the outer surface of CrFK cells
and blocked infection of CrFK cells by ADV-G. In addition, VP2 virion attachment
to CrFK cells was blocked when the VP2 virions were preincubated with partially
purified ABP. Taken together, these results indicate that ABP is a cellular
receptor for ADV.
PMID- 10196279
TI - Intrastrain variants of herpes simplex virus type 1 isolated from a neonate with
fatal disseminated infection differ in the ICP34.5 gene, glycoprotein processing,
and neuroinvasiveness.
AB - Two intrastrain variants of herpes simplex virus type 1 (HSV-1) were isolated
from a newborn with fatal disseminated infection. A small-plaque-producing
variant (SP7) was the predominant virus (>99%) in the brain, and a large-plaque
producing variant (LP5) was the predominant virus (>99%) in the lung and
gastrointestinal tract. EcoRI and BamHI restriction fragment patterns indicated
that SP7 and LP5 are related strains. The large-plaque variants produced plaques
similar in size to those produced by HSV-1 KOS. Unlike LP5 or KOS, SP7 was highly
cell associated and processing of glycoprotein C and glycoprotein D was limited
to precursor forms in infected Vero cells. The large-plaque phenotype from KOS
could be transferred into SP7 by cotransfection of plasmids containing the EK or
JK EcoRI fragment or a 3-kb plasmid with the UL34.5 gene of HSV-1 KOS together
with SP7 DNA. PCR analysis using primers from within the ICP34.5 gene indicated
differences for SP7, LP5, and KOS. Sequencing data indicated two sets of
deletions in the UL34.5 gene that distinguish SP7 from LP5. Both SP7 and LP5
variants were neurovirulent (lethal following intracranial inoculation of young
BALB/c mice); however, the LP5 variant was much less able to cause lethal
neuroinvasive disease (footpad inoculation) whereas KOS caused no disease.
Passage of SP7 selected for viruses (SLP-5 and SLP-10) which were attenuated for
lethal neuroinvasive disease, were not cell-associated, and differed in the
UL34.5 gene. UL34.5 from SLP-5 or SLP-10 resembled that of KOS. These findings
support a role for UL34.5 in promoting virus egress and for neuroinvasive
disease.
PMID- 10196280
TI - Selection of RNA replicons capable of persistent noncytopathic replication in
mammalian cells.
AB - The natural life cycle of alphaviruses, a group of plus-strand RNA viruses,
involves transmission to vertebrate hosts via mosquitoes. Chronic infections are
established in mosquitoes (and usually in mosquito cell cultures), but infection
of susceptible vertebrate cells typically results in rapid shutoff of host mRNA
translation and cell death. Using engineered Sindbis virus RNA replicons
expressing puromycin acetyltransferase as a dominant selectable marker, we
identified mutations allowing persistent, noncytopathic replication in BHK-21
cells. Two of these adaptive mutations involved single-amino-acid substitutions
in the C-terminal portion of nsP2, the viral helicase-protease. At one of these
loci, nsP2 position 726, numerous substitution mutations were created and
characterized in the context of RNA replicons and infectious virus. Our results
suggest a direct correlation between the level of viral RNA replication and
cytopathogenicity. This work also provides a series of alphavirus replicons for
noncytopathic gene expression studies (E. V. Agapov, I. Frolov, B. D. Lindenbach,
B. M. Pragai, S. Schlesinger, and C. M. Rice, Proc. Natl. Acad. Sci. USA 95:12989
12994, 1998) and a general strategy for selecting RNA viral mutants adapted to
different cellular environments.
PMID- 10196282
TI - Activation of promoter P4 of the autonomous parvovirus minute virus of mice at
early S phase is required for productive infection.
AB - Autonomous parvoviruses are tightly dependent on host cell factors for various
steps of their life cycle. In particular, DNA replication and gene expression of
the prototype strain of the minute virus of mice (MVMp) are closely linked to the
onset of host cell DNA replication, pointing to the involvement of an S-phase
specific cellular factor(s) in parvovirus multiplication. The viral nonstructural
protein NS-1 is absolutely required for parvovirus DNA replication and is able to
transcriptionally regulate parvoviral and heterologous promoters. We previously
showed that the promoter P4, which directs the transcription unit encoding the NS
proteins, is activated at the onset of S phase. This activation is dependent on
an E2F motif in the proximal region of promoter P4. An infectious MVM DNA clone
was mutated in the E2F motif of P4. The wild type and the E2F mutant derivative
were tested for their ability to produce progeny viruses after transfection of
permissive cells. In the context of the whole MVMp genome, the E2F mutation
abolished P4 induction in S phase and inactivated the infectious molecular clone,
which failed to become amplified and generate progeny particles. The virus could
be rescued when NS proteins were supplied in trans, showing that P4 hyperactivity
in S is needed to reach a level of NS-1 expression that is sufficient to drive
the viral replication cycle. These data show that E2F-mediated P4 activation at
the early S phase is a limiting factor for parvovirus production. The primary
barrier to parvovirus gene expression in G1 is thought to be promoter formation
rather than activation, due to the poor conversion of the parental single-strand
genome to a duplex form. The S dependence of P4 activation may therefore be a
sign of the virus adaptation to life in the S-phase host cell. If the conversion
block in G1 were to be leaky, the S induction of promoter P4 could be envisioned
as a safeguard against the production of toxic NS proteins until cells reach the
S phase and provide the full machinery for parvovirus replication.
PMID- 10196281
TI - Genetic studies exposing the splicing events involved in herpes simplex virus
type 1 latency-associated transcript production during lytic and latent
infection.
AB - Herpes simplex virus type 1 (HSV-1) establishes latency in sensory neurons, a
state in which the viral lytic genes are silenced and only the latency locus is
transcriptionally active, producing the 2. 0- and 1.5-kb latency-associated
transcripts (LATs). Previous experimental evidence indicates that the LATs are
stable introns, and it has been reported that LAT formation is abolished by
debilitating substitution mutations in the predicted splice sites during lytic
infection but not latency (J. L. Arthur et al., J. Gen. Virol. 79:107-116, 1998).
We have independently studied a set of deletion mutations to explore the roles of
the proposed splice sites during lytic and latent infection. HSV-1 mutant viruses
missing the invariant intron-terminal 5'-G(T/C) or 3'-AG dinucleotides were
analyzed for LAT formation during lytic infection in vitro, when only the 2-kb
LAT is produced, and during latency in mouse trigeminal ganglia, where both LATs
are expressed. Northern blot analysis of total RNAs from different productively
infected cell lines showed that the lytic (2-kb) LAT was not expressed by the
various splice site deletion mutants. In vivo studies using a mouse eye model of
latency similarly showed that the latent (2- and 1. 5-kb) LATs were not expressed
by the mutants. PCR analysis with primers flanking the LAT sequence revealed the
expected splice junction for LAT excision in RNA from sensory neurons latently
infected with wild-type but not mutant virus. Using a virus mutant deleted in the
splicing signals flanking the 556-bp region of LAT whose absence distinguishes
the 1.5- and 2-kb LATs, we observed selective elimination of 1.5-kb LAT
expression in latency, supporting previous suggestions that the internal region
is removed by splicing. Taken together, these results demonstrate that the 2-kb
LAT is formed during both lytic and latent infection by splicing at the predicted
splice sites and that an additional splicing event is involved in the latency
restricted production of the 1.5-kb LAT. We have also mapped the 3' end of the
lytic 2-kb LAT and discuss our results in the context of previous models
addressing the unusual stability of the LATs.
PMID- 10196283
TI - Intracellular formation and processing of the heterotrimeric gH-gL-gO (gCIII)
glycoprotein envelope complex of human cytomegalovirus.
AB - The human cytomegalovirus (HCMV) gCIII complex contains glycoprotein H (gH;
gpUL75), glycoprotein L (gL; gpUL115), and glycoprotein O (gO; gpUL74). To
examine how gH, gL, and gO interact within HCMV-infected cells to assemble the
tripartite complex, pulse-chase experiments were performed. These analyses
demonstrated that gH and gL associate by the end of the pulse period to form a
disulfide dependent gH-gL complex. Subsequently, the gH-gL complex interacts with
a 100-kDa precursor form of gO to form a 220-kDa precursor of the mature gH-gL-gO
complex that contains a 125-kDa form of gO. The 220-kDa precursor complex
(pgCIII) was sensitive to treatment with endoglycosidase H (endo H), while the
mature gCIII complex was essentially resistant to digestion with this enzyme,
suggesting that formation of pgCIII complex occurs in the endoplasmic reticulum
(ER) and is processed to mature gH-gL-gO (gCIII) in a post-ER compartment. While
the N-linked glycans on the 100-kDa form of gO were modified to endo H-resistant
states as the 125-kDa gO formed, additional posttranslational modifications were
detected on gO. These processing alterations were non-N-linked oligosaccharide
modifications that could not be accounted for by phosphorylation or by O
glycosylation of the type sensitive to O-glycanase. Of gH, gL, gO, and the
various complexes that they form, only the mature form of the complex was
detectable at the infected cell membrane, as judged by surface biotinylation
studies.
PMID- 10196285
TI - Highly diverse intergenic regions of the paramyxovirus simian virus 5 cooperate
with the gene end U tract in viral transcription termination and can influence
reinitiation at a downstream gene.
AB - A dicistronic minigenome containing the M-F gene junction was used to determine
the role of the simian virus 5 (SV5) intergenic regions in transcription. The M-F
junction differs from the other SV5 junctions by having a short M gene end U
tract of only four residues (U4 tract) and a 22-base M-F intergenic sequence
between the M gene end and F gene start site. Replacing the 22-base M-F
intergenic region with nonviral sequences resulted in a minigenome template (Rep
22) that was defective in termination at the end of the M gene. Efficient M gene
termination could be restored to the mutant Rep 22 template in either of two
ways: by increasing the U tract length from four to six residues or by restoring
a G residue immediately downstream of the wild-type (WT) U4 tract. In a
dicistronic SH-HN minigenome, a U4-G combination was functionally equivalent to
the naturally occurring SH U6-A gene end in directing SH transcription
termination. In addition to affecting termination, the M-F intergenic region also
influenced polymerase reinitiation. In the context of the WT U4-G M gene end,
substituting nonviral sequences into the M-F intergenic region had a differential
effect on F gene reinitiation, where some but not all nonviral sequences
inhibited reinitiation. The inhibition of F gene reinitiation correlated with
foreign sequences having a high C content. Deleting 6 bases or inserting 18
additional nucleotides into the middle of the 22-base M-F intergenic segment did
not influence M gene termination or F gene reinitiation, indicating that M-F
intergenic length per se is not a important factor modulating the SV5 polymerase
activity. Our results suggest that the sequence diversity at an SV5 gene junction
reflects specific combinations which may differentially affect SV5 gene
expression and provide an additional level of transcriptional control beyond that
which results from the distance of a gene from the 3' end promoter.
PMID- 10196284
TI - Ikappakappa mediates NF-kappaB activation in human immunodeficiency virus
infected cells.
AB - Human monocytes and macrophages are persistent reservoirs of human
immunodeficiency virus (HIV) type-1. Persistent HIV infection of these cells
results in increased levels of NF-kappaB in the nucleus secondary to increased
IkappaBalpha, IkappaBbeta, and IkappaBepsilon degradation, a mechanism postulated
to regulate viral persistence. To characterize the molecular mechanisms
regulating HIV-mediated degradation of IkappaB, we have sought to identify the
regulatory domains of IkappaBalpha targeted by HIV infection. Using monocytic
cells stably expressing different transdominant molecules of IkappaBalpha, we
determined that persistent HIV infection of these cells targets the NH2 but not
the COOH terminus of IkappaBalpha. Further analysis demonstrated that
phosphorylation at S32 and S36 is necessary for HIV-dependent IkappaBalpha
degradation and NF-kappaB activation. Of the putative N-terminal IkappaBalpha
kinases, we demonstrated that the Ikappakappa complex, but not p90(rsk), is
activated by HIV infection and mediates HIV-dependent NF-kappaB activation.
Analysis of viral replication in cells that constitutively express IkappaBalpha
negative transdominant molecules demonstrated a lack of correlation between virus
induced NF-kappaB (p65/p50) nuclear translocation and degree of viral persistence
in human monocytes.
PMID- 10196287
TI - Cooperative interaction of CI protein regulates lysogeny of Lactobacillus casei
by bacteriophage A2.
AB - The temperate bacteriophage A2 forms stable lysogens in Lactobacillus casei. The
A2-encoded cI product (CI), which is responsible for maintaining the A2 prophage
in the lysogenic state, has been purified. The CI protein, which is a monomer of
25.3 kDa in solution, specifically binds to a 153-bp DNA fragment that contains
two divergent promoters, PL and PR. These promoters mediate transcription from cI
and a putative cro, respectively. Three similar, although not identical, 20-bp
inverted repeated DNA segments (operator sites O1, O2, and O3) were found in this
segment. CI selectively interacts with O1, which is placed downstream from the
transcription start point of the cro gene, and with O2 and O3, which overlap with
the -35 region of the two promoters. Using a heterologous RNA polymerase, we have
determined the transcription start points of PL and PR. CI exerts a negative
effect on the in vitro transcription of PR by repositioning the RNA polymerase in
a concentration-dependent manner. CI, when bound to O1 and O2, enhances the
positioning of the RNA polymerase with the PL promoter. Our data indicate that
the CI protein regulates the lytic and lysogenic pathways of the A2 phage.
PMID- 10196286
TI - Role of cellular tumor necrosis factor receptor-associated factors in NF-kappaB
activation and lymphocyte transformation by herpesvirus Saimiri STP.
AB - The STP oncoproteins of the herpesvirus saimiri (HVS) subgroup A strain 11 and
subgroup C strain 488 are now found to be stably associated with tumor necrosis
factor receptor-associated factor (TRAF) 1, 2, or 3. Mutational analyses
identified residues of PXQXT/S in STP-A11 as critical for TRAF association. In
addition, a somewhat divergent region of STP-C488 is critical for TRAF
association. Mutational analysis also revealed that STP-C488 induced NF-kappaB
activation that was correlated with its ability to associate with TRAFs. The HVS
STP-C488 P10-->R mutant was deficient in human T-lymphocyte transformation to
interleukin-2-independent growth but showed wild-type phenotype for marmoset T
lymphocyte transformation in vitro and in vivo. The STP-C488 P10-->R mutant was
also defective in Rat-1 fibroblast transformation, and fibroblast cell
transformation was blocked by a TRAF2 dominant-negative mutant. These data
implicate TRAFs in STP-C488-mediated transformation of human lymphocytes and
rodent fibroblasts. Other factors are implicated in immortalization of common
marmoset T lymphocytes and may also be critical in the transformation of human
lymphocytes and rodent fibroblasts.
PMID- 10196288
TI - Herpes simplex virus transactivator VP16 discriminates between HCF-1 and a novel
family member, HCF-2.
AB - Herpes simplex virus infection is initiated by VP16, a viral transcription factor
that activates the viral immediate-early (IE) genes. VP16 does not recognize the
IE gene promoters directly but instead forms a multiprotein complex with Oct-1
and HCF-1, a ubiquitous nuclear protein required for progression through the G1
phase of the cell cycle. The functional significance of recruiting HCF-1 to the
VP16-induced complex is not understood. Here we describe the identification of a
second HCF-like protein, designated HCF-2. HCF-2 is smaller than HCF-1 but shares
three regions of strong amino acid sequence homology, including the beta
propeller domain required for association with VP16. HCF-2 is expressed in many
tissues, especially the testis, and shows a more dynamic pattern of subcellular
localization than HCF-1. Although HCF-2 associates with VP16 and can support
complex assembly with Oct-1 and DNA, it is significantly less efficient than HCF
1. A similar preference is shown by LZIP, a cellular counterpart of VP16.
Analysis of chimeric proteins showed that differences between the fifth and sixth
kelch repeats of the beta-propeller domains from HCF-1 and HCF-2 dictate this
selectivity. These results reveal an unexpected level of specificity in the
recruitment of HCF-1 to the VP16-induced complex, paralleling the preferential
selection of Oct-1 rather than the closely related POU domain protein Oct-2.
Implications for regulation of the viral life cycle are discussed.
PMID- 10196289
TI - In vitro recoating of reovirus cores with baculovirus-expressed outer-capsid
proteins mu1 and sigma3.
AB - Reovirus outer-capsid proteins mu1, sigma3, and sigma1 are thought to be
assembled onto nascent core-like particles within infected cells, leading to the
production of progeny virions. Consistent with this model, we report the in vitro
assembly of baculovirus-expressed mu1 and sigma3 onto purified cores that lack
mu1, sigma3, and sigma1. The resulting particles (recoated cores, or r-cores)
closely resembled native virions in protein composition (except for lacking cell
attachment protein sigma1), buoyant density, and particle morphology by scanning
cryoelectron microscopy. Transmission cryoelectron microscopy and image
reconstruction of r-cores confirmed that they closely resembled virions in the
structure of the outer capsid and revealed that assembly of mu1 and sigma3 onto
cores had induced rearrangement of the pentameric lambda2 turrets into a
conformation approximating that in virions. r-cores, like virions, underwent
proteolytic conversion to particles resembling native ISVPs (infectious subvirion
particles) in protein composition, particle morphology, and capacity to
permeabilize membranes in vitro. r-cores were 250- to 500-fold more infectious
than cores in murine L cells and, like virions but not ISVPs or cores, were
inhibited from productively infecting these cells by the presence of either NH4Cl
or E-64. The latter results suggest that r-cores and virions used similar routes
of entry into L cells, including processing by lysosomal cysteine proteinases,
even though the former particles lacked the sigma1 protein. To examine the
utility of r-cores for genetic dissections of mu1 functions in reovirus entry, we
generated r-cores containing a mutant form of mu1 that had been engineered to
resist cleavage at the delta:phi junction during conversion to ISVP-like
particles by chymotrypsin in vitro. Despite their deficit in delta:phi cleavage,
these ISVP-like particles were fully competent to permeabilize membranes in vitro
and to infect L cells in the presence of NH4Cl, providing new evidence that this
cleavage is dispensable for productive infection.
PMID- 10196290
TI - Cellular entry of hantaviruses which cause hemorrhagic fever with renal syndrome
is mediated by beta3 integrins.
AB - Hantaviruses replicate primarily in the vascular endothelium and cause two human
diseases, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary
syndrome (HPS). In this report, we demonstrate that the cellular entry of HFRS
associated hantaviruses is facilitated by specific integrins expressed on
platelets, endothelial cells, and macrophages. Infection of human umbilical vein
endothelial cells and Vero E6 cells by the HFRS-causing hantaviruses Hantaan
(HTN), Seoul (SEO), and Puumala (PUU) is inhibited by antibodies to alphavbeta3
integrins and by the integrin ligand vitronectin. The cellular entry of HTN, SEO,
and PUU viruses, but not the nonpathogenic Prospect Hill (PH) hantavirus (i.e., a
virus with no associated human disease), was also mediated by introducting
recombinant alphaIIbbeta3 or alphavbeta3 integrins into beta3-integrin-deficient
CHO cells. In addition, PH infectivity was not inhibited by alphavbeta3-specific
sera or vitronectin but was blocked by alpha5beta1-specific sera and the integrin
ligand fibronectin. RGD tripeptides, which are required for many integrin-ligand
interactions, are absent from all hantavirus G1 and G2 surface glycoproteins, and
GRGDSP peptides did not inhibit hantavirus infectivity. Further, a mouse-human
hybrid beta3 integrin-specific Fab fragment, c7E3 (ReoPro), also inhibited the
infectivity of HTN, SEO, and PUU as well as HPS-associated hantaviruses, Sin
Nombre (SN) and New York-1 (NY-1). These findings indicate that pathogenic HPS-
and HFRS-causing hantaviruses enter cells via beta3 integrins, which are present
on the surfaces of platelets, endothelial cells, and macrophages. Since beta3
integrins regulate vascular permeability and platelet function, these findings
also correlate beta3 integrin usage with common elements of hantavirus
pathogenesis.
PMID- 10196291
TI - Simultaneous infection with retroviruses pseudotyped with different envelope
proteins bypasses viral receptor interference associated with colocalization of
gp70 and target cells on fibronectin CH-296.
AB - Several factors are thought to limit the efficiency of retroviral transduction in
clinical gene therapy protocols that target hematopoietic stem cells. For
example, the level of expression of the amphotropic receptor Pit-2, a phosphate
symporter, appears to be low in human and murine hematopoietic stem cells. We
have previously demonstrated that transduction of hematopoietic cells in the
presence of the fibronectin (FN) fragment CH-296 is extremely efficient (H.
Hanenberg, X. L. Xiao, D. Dilloo, K. Hashino, I. Kato, and D. A. Williams, Nat.
Med. 2:876-882, 1996). To examine functionally whether the retrovirus receptor is
a limiting factor in transduction of hematopoietic cells, we performed
competition experiments in the presence of FN CH-296 with retrovirus vectors
pseudotyped with the same or a different envelope protein. We demonstrate in both
human erythroleukemia (HEL) cells and primary human CD34(+) hematopoietic cells
inhibition of efficient infection due to receptor interference when two vectors
targeting the amphotropic receptor are used simultaneously. Receptor interference
lasted up to 24 h. No interference was demonstrated when vectors targeting the
amphotropic receptor and the gibbon ape leukemia virus (GALV) receptor Pit-1 were
used concurrently. In contrast, simultaneous infection with vectors targeting
both Pit-1 and Pit-2 yielded transduction efficiencies consistently higher than
with either vector alone in both HEL cells and human CD34(+) hematopoietic cells.
These data demonstrate that the use of FN CH-296 leads to amphotropic receptor
saturation in these cells. Simultaneous infection with vectors targeting both
amphotropic and GALV receptors may prove to be of additional benefit in the
design of gene therapy protocols.
PMID- 10196292
TI - Nef enhances human immunodeficiency virus replication and responsiveness to
interleukin-2 in human lymphoid tissue ex vivo.
AB - The nef gene is important for the pathogenicity associated with simian
immunodeficiency virus infection in rhesus monkeys and with human
immunodeficiency virus type 1 (HIV-1) infection in humans. The mechanisms by
which nef contributes to pathogenesis in vivo remain unclear. We investigated the
contribution of nef to HIV-1 replication in human lymphoid tissue ex vivo by
studying infection with parental HIV-1 strain NL4-3 and with a nef mutant
(DeltanefNL4-3). In human tonsillar histocultures, NL4-3 replicated to higher
levels than DeltanefNL4-3 did. Increased virus production with NL4-3 infection
was associated with increased numbers of productively infected cells and greater
loss of CD4(+) T cells over time. While the numbers of productively infected T
cells were increased in the presence of nef, the levels of viral expression and
production per infected T cell were similar whether the nef gene was present or
not. Exogenous interleukin-2 (IL-2) increased HIV-1 production in NL4-3-infected
tissue in a dose-dependent manner. In contrast, DeltanefNL4-3 production was
enhanced only marginally by IL-2. Thus, Nef can facilitate HIV-1 replication in
human lymphoid tissue ex vivo by increasing the numbers of productively infected
cells and by increasing the responsiveness to IL-2 stimulation.
PMID- 10196293
TI - Frequent detection of escape from cytotoxic T-lymphocyte recognition in perinatal
human immunodeficiency virus (HIV) type 1 transmission: the ariel project for the
prevention of transmission of HIV from mother to infant.
AB - Host immunologic factors, including human immunodeficiency virus (HIV)-specific
cytotoxic T lymphocytes (CTL), are thought to contribute to the control of HIV
type 1 (HIV-1) replication and thus delay disease progression in infected
individuals. Host immunologic factors are also likely to influence perinatal
transmission of HIV-1 from infected mother to infant. In this study, the
potential role of CTL in modulating HIV-1 transmission from mother to infant was
examined in 11 HIV-1-infected mothers, 3 of whom transmitted virus to their
offspring. Frequencies of HIV-1-specific human leukocyte antigen class I
restricted CTL responses and viral epitope amino acid sequence variation were
determined in the mothers and their infected infants. Maternal HIV-1-specific CTL
clones were derived from each of the HIV-1-infected pregnant women. Amino acid
substitutions within the targeted CTL epitopes were more frequently identified in
transmitting mothers than in nontransmitting mothers, and immune escape from CTL
recognition was detected in all three transmitting mothers but in only one of
eight nontransmitting mothers. The majority of viral sequences obtained from the
HIV-1-infected infant blood samples were susceptible to maternal CTL. These
findings demonstrate that epitope amino acid sequence variation and escape from
CTL recognition occur more frequently in mothers that transmit HIV-1 to their
infants than in those who do not. However, the transmitted virus can be a CTL
susceptible form, suggesting inadequate in vivo immune control.
PMID- 10196294
TI - Complete sequence of enzootic nasal tumor virus, a retrovirus associated with
transmissible intranasal tumors of sheep.
AB - The sequence of the complete genome of ovine enzootic nasal tumor virus, an
exogenous retrovirus associated exclusively with contagious intranasal tumors of
sheep, was determined. The genome is 7,434 nucleotides long and exhibits a
genetic organization characteristic of type B and D oncoviruses. Enzootic nasal
tumor virus is closely related to the Jaagsiekte sheep retrovirus and to sheep
endogenous retroviruses.
PMID- 10196295
TI - Gene therapy vectors based on adeno-associated virus type 1.
AB - The complete sequence of adeno-associated virus type 1 (AAV-1) was defined. Its
genome of 4,718 nucleotides demonstrates high homology with those of other AAV
serotypes, including AAV-6, which appears to have arisen from homologous
recombination between AAV-1 and AAV-2. Analysis of sera from nonhuman and human
primates for neutralizing antibodies (NAB) against AAV-1 and AAV-2 revealed the
following. (i) NAB to AAV-1 are more common than NAB to AAV-2 in nonhuman
primates, while the reverse is true in humans; and (ii) sera from 36% of nonhuman
primates neutralized AAV-1 but not AAV-2, while sera from 8% of humans
neutralized AAV-2 but not AAV-1. An infectious clone of AAV-1 was isolated from a
replicated monomer form, and vectors were created with AAV-2 inverted terminal
repeats and AAV-1 Rep and Cap functions. Both AAV-1- and AAV-2-based vectors
transduced murine liver and muscle in vivo; AAV-1 was more efficient for muscle,
while AAV-2 transduced liver more efficiently. Strong NAB responses were detected
for each vector administered to murine skeletal muscle; these responses prevented
readministration of the same serotype but did not substantially cross-neutralize
the other serotype. Similar results were observed in the context of liver
directed gene transfer, except for a significant, but incomplete, neutralization
of AAV-1 from a previous treatment with AAV-2. Vectors based on AAV-1 may be
preferred in some applications of human gene therapy.
PMID- 10196296
TI - Jaagsiekte retrovirus is widely distributed both in T and B lymphocytes and in
mononuclear phagocytes of sheep with naturally and experimentally acquired
pulmonary adenomatosis.
AB - Jaagsiekte sheep retrovirus (JSRV) is a type D retrovirus specifically associated
with a contagious lung tumor of sheep, sheep pulmonary adenomatosis (SPA). JSRV
replicates actively in the transformed epithelial cells of the lung, and JSRV DNA
and RNA have been detected in lymphoid tissues of naturally affected animals. To
determine the lymphoid target cells of JSRV, CD4(+) T cells, CD8(+) T cells, B
lymphocytes, and adherent cell (macrophage/monocyte) populations were isolated
from the mediastinal lymph nodes of naturally affected sheep and lambs inoculated
with JSRV. Cells were enriched to high purity and then analyzed for JSRV proviral
DNA by heminested PCR, and the proviral burden was quantitated by limiting
dilution analysis. JSRV proviral DNA was found in all subsets examined but not in
appropriate negative controls. In sheep naturally affected with SPA, JSRV
proviral burden was greatest in the adherent cell population. In the nonadherent
lymphocyte population, surface immunoglobulin-positive B cells contained the
greatest proviral burden, while CD4(+) and CD8(+) T cells contained the lowest
levels of JSRV proviral DNA. In most of the cases (5 of 8), provirus also could
be detected in the peripheral blood mononuclear cell (PBMC) population. A kinetic
study of JSRV infection in the mediastinal lymphocyte population of newborn lambs
inoculated with JSRV found that JSRV proviral DNA could be detected as early as 7
days postinoculation before the onset of pulmonary adenomatosis, although the
proviral burden was greatly reduced compared to adult natural cases. This was
reflected in the levels found in PBMC since proviral DNA was detected in 2 of 13
animals. At the early time points studied (7 to 28 days postinoculation) no one
subset was preferentially infected. These data indicate that JSRV can infect
lymphoid and phagocytic mononuclear cells of sheep and that dissemination
precedes tumor formation. Infection of lymphoid tissue, therefore, may play an
important role in the pathogenesis of SPA.
PMID- 10196297
TI - Protection of Macaques against pathogenic simian/human immunodeficiency virus
89.6PD by passive transfer of neutralizing antibodies.
AB - The role of antibody in protection against human immunodeficiency virus (HIV-1)
has been difficult to study in animal models because most primary HIV-1 strains
do not infect nonhuman primates. Using a chimeric simian/human immunodeficiency
virus (SHIV) based on the envelope of a primary isolate (HIV-89.6), we performed
passive-transfer experiments in rhesus macaques to study the role of anti
envelope antibodies in protection. Based on prior in vitro data showing
neutralization synergy by antibody combinations, we evaluated HIV immune globulin
(HIVIG), and human monoclonal antibodies (MAbs) 2F5 and 2G12 given alone,
compared with the double combination 2F5/2G12 and the triple combination
HIVIG/2F5/2G12. Antibodies were administered 24 h prior to intravenous challenge
with the pathogenic SHIV-89.6PD. Six control monkeys displayed high plasma
viremia, rapid CD4(+)-cell decline, and clinical AIDS within 14 weeks. Of six
animals given HIVIG/2F5/2G12, three were completely protected; the remaining
three animals became SHIV infected but displayed reduced plasma viremia and near
normal CD4(+)-cell counts. One of three monkeys given 2F5/2G12 exhibited only
transient evidence of infection; the other two had marked reductions in viral
load. All monkeys that received HIVIG, 2F5, or 2G12 alone became infected and
developed high-level plasma viremia. However, compared to controls, monkeys that
received HIVIG or MAb 2G12 displayed a less profound drop in CD4(+) T cells and a
more benign clinical course. These data indicate a general correlation between in
vitro neutralization and protection and suggest that a vaccine that elicits
neutralizing antibody should have a protective effect against HIV-1 infection or
disease.
PMID- 10196298
TI - Human herpesvirus 6 infects dendritic cells and suppresses human immunodeficiency
virus type 1 replication in coinfected cultures.
AB - Human herpesvirus 6 (HHV-6) has been implicated as a cofactor in the progressive
loss of CD4(+) T cells observed in AIDS patients. Because dendritic cells (DC)
play an important role in the immunopathogenesis of human immunodeficiency virus
(HIV) disease, we studied the infection of DC by HHV-6 and coinfection of DC by
HHV-6 and HIV. Purified immature DC (derived from adherent peripheral blood
mononuclear cells in the presence of granulocyte-macrophage colony-stimulating
factor and interleukin-4) could be infected with HHV-6, as determined by PCR
analyses, intracellular monoclonal antibody staining, and presence of virus in
culture supernatants. However, HHV-6-infected DC demonstrated neither cytopathic
changes nor functional defects. Interestingly, HHV-6 markedly suppressed HIV
replication and syncytium formation in coinfected DC cultures. This HHV-6
mediated anti-HIV effect was DC specific, occurred when HHV-6 was added either
before or after HIV, and was not due to decreased surface expression or function
of CD4, CXCR4, or CCR5. Conversely, HIV had no demonstrable effect on HHV-6
replication. These findings suggest that HHV-6 may protect DC from HIV-induced
cytopathicity in AIDS patients. We also demonstrate that interactions between HIV
and herpesviruses are complex and that the observable outcome of dual infection
is dependent on the target cell type.
PMID- 10196300
TI - Immunotyping of human immunodeficiency virus type 1 (HIV): an approach to
immunologic classification of HIV.
AB - Because immunologic classification of human immunodeficiency virus type 1 (HIV)
might be more relevant than genotypic classification for designing polyvalent
vaccines, studies were undertaken to determine whether immunologically defined
groups of HIV ("immunotypes") could be identified. For these experiments, the V3
region of the 120-kDa envelope glycoprotein (gp120) was chosen for study.
Although antibodies (Abs) to V3 may not play a major protective role in
preventing HIV infection, identification of a limited number of immunologically
defined structures in this extremely variable region would set a precedent
supporting the hypothesis that, despite its diversity, the HIV family, like the
V3 region, might be divisible into immunotypes. Consequently, the immunochemical
reactivities of 1,176 combinations of human anti-V3 monoclonal Abs (MAbs) and V3
peptides, derived from viruses of several clades, were studied. Extensive cross
clade reactivity was observed. The patterns of reactivities of 21 MAbs with 50
peptides from clades A through H were then analyzed by a multivariate statistical
technique. To test the validity of the mathematical approach, a cluster analysis
of the 21 MAbs was performed. Five groups were identified, and these MAb clusters
corresponded to classifications of these same MAbs based on the epitopes which
they recognize. The concordance between the MAb clusters identified by
mathematical analysis and by their specificities supports the validity of the
mathematical approach. Therefore, the same mathematical technique was used to
identify clusters within the 50 peptides. Seven groups of peptides, each
containing peptides from more than one clade, were defined. Inspection of the
amino acid sequences of the peptides in each of the mathematically defined
peptide clusters revealed unique "signature sequences" that suggest structural
motifs characteristic of each V3-based immunotype. The results suggest that
cluster analysis of immunologic data can define immunotypes of HIV. These
immunotypes are distinct from genotypic classifications. The methods described
pave the way for identification of immunotypes defined by immunochemical and
neutralization data generated with anti-HIV Env MAbs and intact, viable HIV
virions.
PMID- 10196299
TI - Alpha interferon inhibits human herpesvirus 8 (HHV-8) reactivation in primary
effusion lymphoma cells and reduces HHV-8 load in cultured peripheral blood
mononuclear cells.
AB - Infection by human herpesvirus 8 (HHV-8) is associated with the development of
Kaposi's sarcoma (KS). Since regression of KS can be achieved by treatment of the
patients with alpha interferon (IFN-alpha), we analyzed the effects of IFN-alpha
or anti-IFN-alpha antibodies (Ab) on HHV-8 latently infected primary effusion
lymphoma-derived cell lines (BCBL-1 and BC-1) and on peripheral blood mononuclear
cells (PBMC) from patients with all forms of KS and from at-risk subjects. IFN
alpha inhibited in a dose-dependent manner the amplification of HHV-8 DNA in BCBL
1 cells induced to lytic infection with tetradecanoyl phorbol acetate (TPA). This
effect was associated with the inhibition of the expression of HHV-8 nut-1 and
kaposin genes that are induced early and several hours, respectively, after TPA
treatment. In addition, IFN-alpha inhibited virus production and/or release from
BCBL-1 cells. Inhibition of nut-1 and kaposin genes by IFN-alpha was also
observed in BC-1 cells induced with n-butyrate. Conversely, the addition of anti
IFN-alpha Ab to TPA-induced BCBL-1 cells resulted in a larger number of mature
enveloped particles and in a more extensive cytopathic effect due to the
neutralization of the endogenous IFN produced by these cells. IFN was also
produced by cultured PBMC from HHV-8-infected individuals, and this was
associated with a loss of viral DNA during culture. However, the addition of anti
IFN-alpha Ab or anti-type I IFN receptor Ab promoted the maintenance of HHV-8 DNA
in these cells that was associated with the detection of the latency-associated
kaposin RNA. Finally, the addition of IFN-alpha reduced the HHV-8 load in PBMC.
Thus, IFN-alpha appears to have inhibitory effects on HHV-8 persistent infection
of PBMC. These results suggest that, in addition to inhibiting the expression of
angiogenic factors that are key to KS development, IFN-alpha may induce KS
regression by reducing the HHV-8 load and/or inhibiting virus reactivation.
PMID- 10196301
TI - In vitro infection of human peripheral blood mononuclear cells by GB virus
C/Hepatitis G virus.
AB - GB virus C (GBV-C), also known as hepatitis G virus, is a recently discovered
flavivirus-like RNA agent with unclear pathogenic implications. To investigate
whether human peripheral blood mononuclear cells (PBMC) are susceptible to in
vitro GBV-C infection, we have incubated PBMC from four healthy blood donors with
a human GBV-C RNA-positive serum. By means of (i) strand-specific reverse
transcription-PCR, cloning, and sequencing; (ii) sucrose ultracentrifugation and
RNase sensitivity assays; (iii) fluorescent in situ hybridization; and (iv)
Western blot analysis, it has been demonstrated that GBV-C is able to infect in
vitro cells and replicate for as long as 30 days under the conditions developed
in our cell culture system. The concentration of GBV-C RNA increased during the
second and third weeks of culture. The titers of the genomic strand were 10 times
higher than the titers of the antigenomic strand. In addition, the same
predominant GBV-C sequence was found in all PBMC cultures and in the in vivo-GBV
C-infected PBMC isolated from the donor of the inoculum. GBV-C-specific
fluorescent in situ hybridization signals were confined to the cytoplasm of cells
at different times during the culture period. Finally, evidence obtained by
sucrose ultracentrifugation, RNase sensitivity assays, and Western blot analysis
of the culture supernatants suggests that viral particles are released from in
vitro-GBV-C-infected PBMC. In conclusion, our study has demonstrated, for the
first time, GBV-C replication in human lymphoid cells under experimental in vitro
infection conditions.
PMID- 10196303
TI - Mutational analysis of glycosylation, membrane translocation, and cell surface
expression of the hepatitis E virus ORF2 protein.
AB - Hepatitis E virus (HEV) is the etiological agent for viral hepatitis type E,
which is a major problem in the developing world. Because HEV cannot be cultured
in vitro, very little information exists on the mechanisms of HEV gene expression
and genome replication. HEV is a positive-strand RNA virus with three potential
open reading frames (ORFs), one of which (ORF2) is postulated to encode the major
viral capsid protein (pORF2). We earlier showed (S. Jameel, M. Zafrullah, M. H.
Ozdener, and S. K. Panda, J. Virol. 70:207-216, 1996) pORF2 to be a approximately
88-kDa glycoprotein, carrying N-linked glycans and a potential endoplasmic
reticulum (ER)-directing signal at its N terminus. Treatment with the drugs
brefeldin A and monensin suggest that the protein may accumulate within the ER.
Based on mutational analysis, we demonstrate Asn-310 to be the major site of N
glycan addition. In COS-1 cell expression and in vitro translation experiments,
we confirm the ER-translocating nature of the pORF2 N-terminal hydrophobic
sequence and show that the protein is cotranslationally, but not
posttranslationally, translocated across the ER membrane. Earlier, we had also
demonstrated cell surface localization of a fraction of the COS-1 cell-expressed
pORF2. Using glycosylation- and translocation-defective mutants of pORF2, we now
show that while transit of pORF2 into the ER is necessary for its cell surface
expression, glycosylation of the protein is not required for such localization.
These results may offer clues to the mechanisms of gene expression and capsid
assembly in HEV.
PMID- 10196302
TI - Functional dissection of CCR5 coreceptor function through the use of CD4
independent simian immunodeficiency virus strains.
AB - With rare exceptions, all simian immunodeficiency virus (SIV) strains can use
CCR5 as a coreceptor along with CD4 for viral infection. In addition, many SIV
strains are capable of using CCR5 as a primary receptor to infect CD4-negative
cells such as rhesus brain capillary endothelial cells. By using coupled
fluorescence-activated cell sorter (FACS) and infection assays, we found that
even very low levels of CCR5 expression could support CD4-independent virus
infection. CD4-independent viruses represent valuable tools for finely dissecting
interactions between Env and CCR5 which may otherwise be masked due to the
stabilization of these contacts by Env-CD4 binding. Based on the ability of SIV
Env to bind to and mediate infection of cells expressing CCR5 chimeras and
mutants, we identified the N terminus of CCR5 as a critical domain for direct Env
binding and for supporting CD4-independent virus infection. However, the activity
of N-terminal domain CCR5 mutants could be rescued by the presence of CD4,
indicating that other regions of CCR5 are important for post-binding events that
lead to viral entry. Rhesus CCR5 supported CD4-independent infection and direct
Env binding more efficiently than did human CCR5 due to a single amino acid
difference in the N terminus. Interestingly, uncleaved, oligomeric SIV Env
protein bound to both CD4 and CCR5 less efficiently than did monomeric gp120.
Finally, several mutations present in chronically infected monkey populations are
shown to decrease the ability of CCR5 to serve as a primary viral receptor for
the SIV isolates examined.
PMID- 10196304
TI - Design of 5' untranslated sequences in retroviral vectors developed for medical
use.
AB - Utilizing genetic modules of simple retroviruses, we have developed a novel
generation of gene transfer vectors with improved therapeutic potential. In the
5' untranslated "leader" sequences, all AUG codons which may aberrantly initiate
translation and all viral coding sequences were removed. Thus, the probability of
expressing unwanted peptides and the potential for homologous recombination with
retroviral genes were largely reduced, and the cloning capacity was increased.
The transgene was inserted to replace the viral gag sequences, and a new minimal
splice acceptor was introduced, resulting in increased expression with all genes
tested (those coding for human multidrug resistance 1 and enhanced green
fluorescent protein, as well as the lacZ gene). These vectors may represent
attractive tools for human gene therapy, because they increase the efficiency of
transgene expression and may also increase safety in medical applications.
PMID- 10196305
TI - The C-terminal region but not the Arg-X-Pro repeat of Epstein-Barr virus protein
EB2 is required for its effect on RNA splicing and transport.
AB - The Epstein-Barr virus BMLF1 gene product EB2 has been shown to efficiently
transform immortalized Rat1 and NIH 3T3 cells, to bind RNA, and to shuttle from
the nucleus to the cytoplasm. In transient-expression assays EB2 seems to affect
mRNA nuclear export of intronless RNAs and pre-mRNA 3' processing, but no direct
proof of EB2 being involved in RNA processing and transport has been provided,
and no specific functional domain of EB2 has been mapped. Here we significantly
extend these findings and directly demonstrate that (i) EB2 inhibits the
cytoplasmic accumulation of mRNAs, but only if they are generated from precursors
containing weak (cryptic) 5' splice sites, (ii) EB2 has no effect on the
cytoplasmic accumulation of mRNA generated from precursors containing
constitutive splice sites, and (iii) EB2 has no effect on the 3' processing of
precursor RNAs containing canonical and noncanonical cleavage-polyadenylation
signals. We also show that in the presence of EB2, intron-containing and
intronless RNAs accumulate in the cytoplasm. EB2 contains an Arg-X-Pro tripeptide
repeated eight times, similar to that described as an RNA-binding domain in the
herpes simplex virus type 1 protein US11. As glutathione S-transferase fusion
proteins, both EB2 and the Arg-X-Pro repeat bound RNA in vitro. However, by using
EB2 deletion mutants, we demonstrated that the effect of EB2 on splicing and RNA
transport requires the C-terminal half of the protein but not the Arg-X-Pro
repeat.
PMID- 10196306
TI - Human immunodeficiency virus type 1 (HIV-1) Vpr functions as an immediate-early
protein during HIV-1 infection.
AB - Human immunodeficiency virus type 1 (HIV-1) Vpr is a virion-associated protein
which facilitates HIV-1 infection of nondividing cells by contributing to the
nuclear transport of the preintegration complex (PIC). Vpr was also shown to
induce a cell cycle G2 arrest in infected proliferating cells that optimizes HIV
1 long terminal repeat (LTR)-directed gene expression and viral production.
However, it is unclear whether this activity is mediated primarily early by
virion-associated Vpr or alternatively late during infection when Vpr is de novo
expressed. We report here that in the absence of de novo expression, virion
associated Vpr induces a transient G2 arrest that can subsequently lead to cell
killing by apoptosis. Interestingly, the induction of both cell cycle G2 arrest
and apoptosis by virion-associated Vpr requires viral entry but not viral
replication, since reverse transcriptase and protease inhibitor treatments do not
prevent these Vpr effects. These results raise the possibility that in vivo both
infectious and noninfectious viruses contribute to the dysfunction and killing of
CD4(+) cells. In addition, our results reveal that virion-associated Vpr
stimulates viral replication in proliferating cells after establishing a cell
cycle G2 arrest by increasing LTR-directed gene expression. Importantly, this Vpr
mediated LTR activation appears to be a requirement for subsequent optimal Tat
transactivation. Taken together, these results strongly suggest that in addition
to participating in the HIV PIC nuclear transport in nondividing cells, virion
associated Vpr activates HIV-1 LTR-directed gene expression by manipulating the
host cell cycle. From this, we conclude that Vpr functions as an immediate-early
protein during HIV-1 infection.
PMID- 10196307
TI - Live-cell analysis of a green fluorescent protein-tagged herpes simplex virus
infection.
AB - Many stages of the herpes simplex virus maturation pathway have not yet been
defined. In particular, little is known about the assembly of the virion tegument
compartment and its subsequent incorporation into maturing virus particles. Here
we describe the construction of a herpes simplex virus type 1 (HSV-1) recombinant
in which we have replaced the gene encoding a major tegument protein, VP22, with
a gene expressing a green fluorescent protein (GFP)-VP22 fusion protein (GFP-22).
We show that this virus has growth properties identical to those of the parental
virus and that newly synthesized GFP-22 is detectable in live cells as early as 3
h postinfection. Moreover, we show that GFP-22 is incorporated into the HSV-1
virion as efficiently as VP22, resulting in particles which are visible by
fluorescence microscopy. Consequently, we have used time lapse confocal
microscopy to monitor GFP-22 in live-cell infection, and we present time lapse
animations of GFP-22 localization throughout the virus life cycle. These
animations demonstrate that GFP-22 is present in a diffuse cytoplasmic location
when it is initially expressed but evolves into particulate material which
travels through an exclusively cytoplasmic pathway to the cell periphery. In this
way, we have for the first time visualized the trafficking of a herpesvirus
structural component within live, infected cells.
PMID- 10196308
TI - CpG-containing oligonucleotides are efficient adjuvants for induction of
protective antiviral immune responses with T-cell peptide vaccines.
AB - Synthetic nonmethylated oligonucleotides containing CpG dinucleotides (CpG-ODNs)
have been shown to exhibit immunostimulatory activity. CpG-ODNs have the capacity
to directly activate B cells, macrophages, and dendritic cells, and we show here
that this is reflected by cell surface binding of oligonucleotides to these cell
subsets. However, T cells are not directly activated by CpG-ODNs, which
correlates with the failure to bind to the T-cell surface. Efficient competition
for CpG-induced B-cell activation by non-CpG-containing oligonucleotides suggests
that oligonucleotides might bind to an as yet undefined sequence-nonspecific
receptor prior to cellular activation. Induction of protective T-cell responses
against challenge infection with lymphocytic choriomeningitis virus (LCMV) or
with recombinant vaccinia virus expressing the LCMV glycoprotein was achieved by
immunizing mice with the immunodominant major histocompatibility complex class I
binding LCMV glycoprotein-derived peptide gp33 together with CpG-ODNs. In these
experiments, B cells, potentially serving as CpG-ODN-activated antigen-presenting
cells (APCs), were not required for induction of protective immunity since CpG
ODN-gp33-immunized B-cell-deficient mice were equally protected against challenge
infection with both viruses. This finding suggested that macrophages and/or
dendritic cells were sufficiently activated in vivo by CpG-ODNs to serve as
potent APCs for the induction of naive T cells. Furthermore, treatment with CpG
ODN alone induced protection against infection with Listeria monocytogenes via
antigen-independent activation of macrophages. These data suggest that CpG
activation of macrophages and dendritic cells may provide a critical step in CpG
ODN adjuvant activity.
PMID- 10196309
TI - An intact TAR element and cytoplasmic localization are necessary for efficient
packaging of human immunodeficiency virus type 1 genomic RNA.
AB - Although most reports defining the human immunodeficiency virus type 1 (HIV-1)
genomic RNA packaging signal have focused on the region downstream of the major
5' splice site, others have suggested that sequences upstream of the splice site
may also play an important role. In this study we have directly examined the role
played by the HIV-1 TAR region in RNA packaging. For these experiments we used a
proviral expression system that is largely independent of Tat for transcriptional
activation. This allowed us to create constructs that efficiently expressed RNAs
carrying mutations in TAR and to determine the ability of these RNAs to be
packaged. Our results indicate that loss of sequences in TAR significantly reduce
the ability of a viral RNA to be packaged. The requirement for TAR sequences in
RNA packaging was further examined by using a series of missense mutations
positioned throughout the entire TAR structure. TAR mutations previously shown to
influence Tat transactivation, such as G31U in the upper loop region or UCU to
AAG in the bulge (nucleotides [nt] 22 to 24), failed to have any effect on RNA
packaging. Mutations which disrupted the portion of the TAR stem immediately
below the bulge also had little effect. In contrast, dramatic effects on RNA
packaging were observed with constructs containing mutations in the lower portion
of the TAR stem. Point mutations which altered nt 5 to 9, 10 to 15, 44 to 49, or
50 to 54 all reduced RNA packaging 11- to 25-fold. However, compensatory double
mutations which restored the stem structure were able to restore packaging. These
results indicate that an intact lower stem structure, rather than a specific
sequence, is required for RNA packaging. Our results also showed that RNA
molecules retained within the nucleus cannot be packaged, unless they are
transported to the cytoplasm by either Rev/Rev response element or the Mason
Pfizer monkey virus constitutive transport element.
PMID- 10196310
TI - Binding of human immunodeficiency virus type 1 Gag to membrane: role of the
matrix amino terminus.
AB - Binding of the human immunodeficiency virus type 1 (HIV-1) Gag protein precursor,
Pr55(Gag), to membrane is an indispensable step in virus assembly. Previously, we
reported that a matrix (MA) residue 6 substitution (6VR) imposed a virus assembly
defect similar to that observed with myristylation-defective mutants, suggesting
that the 6VR change impaired membrane binding. Intriguingly, the 6VR mutation had
no effect on Gag myristylation. The defective phenotype imposed by 6VR was
reversed by changes at other positions in MA, including residue 97. In this
study, we use several biochemical methods to demonstrate that the residue 6
mutation, as well as additional substitutions in MA amino acids 7 and 8, reduce
membrane binding without affecting N-terminal myristylation. This effect is
observed in the context of Pr55(Gag), a truncated Gag containing only MA and CA,
and in MA itself. The membrane binding defect imposed by the 6VR mutation is
reversed by second-site changes in MA residues 20 and 97, both of which, when
present alone, increase membrane binding to levels greater than those for the
wild type. Both reduced and enhanced membrane binding imposed by the MA
substitutions depend upon the presence of the N-terminal myristate. The results
support the myristyl switch model recently proposed for the regulation of Gag
membrane binding, according to which membrane binding is determined by the degree
of exposure or sequestration of the N-terminal myristate moiety. Alternatively,
insertion of the myristate into the lipid bilayer might be a prerequisite event
for the function of other distinct MA-encoded membrane binding domains.
PMID- 10196311
TI - Differential inhibition of human immunodeficiency virus type 1 fusion, gp120
binding, and CC-chemokine activity by monoclonal antibodies to CCR5.
AB - The CC-chemokine receptor CCR5 mediates fusion and entry of the most commonly
transmitted human immunodeficiency virus type 1 (HIV-1) strains. We have isolated
six new anti-CCR5 murine monoclonal antibodies (MAbs), designated PA8, PA9, PA10,
PA11, PA12, and PA14. A panel of CCR5 alanine point mutants was used to map the
epitopes of these MAbs and the previously described MAb 2D7 to specific amino
acid residues in the N terminus and/or second extracellular loop regions of CCR5.
This structural information was correlated with the MAbs' abilities to inhibit
(i) HIV-1 entry, (ii) HIV-1 envelope glycoprotein-mediated membrane fusion, (iii)
gp120 binding to CCR5, and (iv) CC-chemokine activity. Surprisingly, there was no
correlation between the ability of a MAb to inhibit HIV-1 fusion-entry and its
ability to inhibit either the binding of a gp120-soluble CD4 complex to CCR5 or
CC-chemokine activity. MAbs PA9 to PA12, whose epitopes include residues in the
CCR5 N terminus, strongly inhibited gp120 binding but only moderately inhibited
HIV-1 fusion and entry and had no effect on RANTES-induced calcium mobilization.
MAbs PA14 and 2D7, the most potent inhibitors of HIV-1 entry and fusion, were
less effective at inhibiting gp120 binding and were variably potent at inhibiting
RANTES-induced signaling. With respect to inhibiting HIV-1 entry and fusion, PA12
but not PA14 was potently synergistic when used in combination with 2D7, RANTES,
and CD4-immunoglobulin G2, which inhibits HIV-1 attachment. The data support a
model wherein HIV-1 entry occurs in three stages: receptor (CD4) binding,
coreceptor (CCR5) binding, and coreceptor-mediated membrane fusion. The
antibodies described will be useful for further dissecting these events.
PMID- 10196312
TI - High-level variability in the ORF-K1 membrane protein gene at the left end of the
Kaposi's sarcoma-associated herpesvirus genome defines four major virus subtypes
and multiple variants or clades in different human populations.
AB - Infection with Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) or human
herpesvirus 8 (HHV8) is common in certain parts of Africa, the Middle East, and
the Mediterranean, but is rare elsewhere, except in AIDS patients. Nevertheless,
HHV8 DNA is found consistently in nearly all classical, endemic, transplant and
AIDS-associated KS lesions as well as in some rare AIDS-associated lymphomas. The
concept that HHV8 genomes fall into several distinct subgroups has been confirmed
and refined by PCR DNA sequence analysis of the ORF-K1 gene encoding a highly
variable glycoprotein related to the immunoglobulin receptor family that maps at
the extreme left-hand end of the HHV-8 genome. Among more than 60 different tumor
samples from the United States, central Africa, Saudi Arabia, Taiwan, and New
Zealand, amino acid substitutions were found at a total of 62% of the 289 amino
acid positions. These variations defined four major subtypes and 13 distinct
variants or clades similar to those found for the HIV ENV protein. The B and D
subtype ORF-K1 proteins differ from the A and C subtypes by 30 and 24%,
respectively, whereas A and C differ from each other by 15%. In all cases tested,
multiple samples from the same patient were identical. Examples of the B subtype
were found almost exclusively in KS patients from Africa or of African heritage,
whereas the rare D subtypes were found only in KS patients of Pacific Island
heritage. In contrast, C subtypes were found predominantly in classic KS and in
iatrogenic and AIDS KS in the Middle East and Asia, whereas U.S. AIDS KS samples
were primarily A1, A4, and C3 variants. We conclude that this unusually high
diversity, in which 85% of the nucleotide changes lead to amino acid changes,
reflects some unknown powerful biological selection process that has been acting
preferentially on this early lytic cycle membrane signalling protein. Two
distinct levels of ORF-K1 variability are recognizable. Subtype-specific
variability indicative of long-term evolutionary divergence is both spread
throughout the protein as well as concentrated within two 40-amino-acid
extracellular domain variable regions (VR1 and VR2), whereas intratypic
variability localizes predominantly within a single 25-amino-acid hypervariable
Cys bridge loop and apparently represents much more recent changes that have
occurred even within specific clades. In contrast, numerous extracellular domain
glycosylation sites and Cys bridge residues as well as the ITAM motif in the
cytoplasmic domain are fully conserved. Overall, we suggest that rather than
being a newly acquired human pathogen, HHV8 is an ancient human virus that is
preferentially transmitted in a familial fashion and is difficult to transmit
horizontally in the absence of immunosuppression. The division into the four
major HHV8 subgroups is probably the result of isolation and founder effects
associated with the history of migration of modern human populations out of
Africa over the past 35,000 to 60,000 years.
PMID- 10196313
TI - Human corneal cells and other fibroblasts can stimulate the appearance of herpes
simplex virus from quiescently infected PC12 cells.
AB - A two-cell system for the stimulation of herpes simplex virus type 1 (HSV-1) from
an in vitro model of long-term (quiescent) infection is described. Rat
pheochromocytoma (PC12) cells differentiated with nerve growth factor were
infected with HSV-1 strain 17. Little, if any, cytotoxicity was observed, and a
quiescent infection was established. The long-term infection was characterized by
the absence of all detectable virus in the culture medium and little, if any,
detectable early or late viral-gene expression as determined by reverse
transcriptase PCR analysis. The presence of HSV-1 DNA was determined by PCR
analysis. This showed that approximately 180 viral genomes were present in
limiting dilutions where as few as 16 cells were examined. The viral DNA was
infectious, since cocultivation with human corneal fibroblasts (HCF) or human
corneal epithelial cells (HCE) resulted in recovery of virus from most, if not
all, clusters of PC12 cells. Following cocultivation, viral antigens appeared
first on PC12 cells and then on neighboring inducing cells, as determined by
immunofluorescent staining, demonstrating that de novo viral protein synthesis
first occurred in the long-term-infected PC12 cells. Interestingly, the ability
to induce HSV varied among the cell lines tested. For example, monkey kidney CV-1
cells and human hepatoblastoma HepG2 cells, but not mouse neuroblastoma cells or
undifferentiated PC12 cells, mediated stimulation. This work thus shows that (i)
quiescent HSV infections can be maintained in PC12 cells in vitro, (ii) HSV can
be induced from cells which do not accumulate significant levels of latency
associated transcripts, and (iii) the activation of HSV gene expression can be
induced via neighboring cells. The ability of adjacent cells to stimulate HSV
gene expression in neuron-like cells represents a novel area of study. The
mechanism(s) whereby HCF, HCE, and HepG2 and CV-1 cells communicate with PC12
cells and stimulate viral replication, as well as how this system compares with
other in vitro models of long-term infection, is discussed.
PMID- 10196314
TI - Cellular tropism and viral interleukin-6 expression distinguish human herpesvirus
8 involvement in Kaposi's sarcoma, primary effusion lymphoma, and multicentric
Castleman's disease.
AB - Human herpesvirus 8 (HHV-8) infection has been implicated in the etiology of
Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and multicentric
Castleman's disease (MCD), three diseases that frequently develop in
immunocompromised, human immunodeficiency virus-positive individuals. One
hypothesis that would account for different pathological manifestations of
infection by the same virus is that viral genes are differentially expressed in
heterogeneous cell types. To test this hypothesis, we analyzed the localization
and levels of expression of two viral genes expressed in latent and lytic
infections and the viral homologue of interleukin-6 (vIL-6). We show that PEL
parallels KS in the pattern of latent and lytic cycle viral gene expression but
that the predominant infected cell type is a B cell. We also show that MCD
differs from KS not only in the infected cell type (B-cell and T-cell lineage)
but also in the pattern of viral gene expression. Only a few cells in the lesion
are infected and all of these cells express lytic-cycle genes. Of possibly
greater significance is the fact that in a comparison of KS, PEL, and MCD, we
found dramatic differences in the levels of expression of vIL-6. Interleukin-6 is
a B-cell growth and differentiation factor whose altered expression has been
linked to plasma cell abnormalities, as well as myeloid and lymphoid
malignancies. Our findings support the hypothesis that HHV-8 plays an important
role in the pathogenesis of PEL and MCD, in which vIL-6 acts as an autocrine or
paracrine factor in the lymphoproliferative processes common to both.
PMID- 10196316
TI - Characterization of Varicella-Zoster virus glycoprotein K (open reading frame 5)
and its role in virus growth.
AB - Varicella-zoster virus (VZV) is an alphaherpesvirus that is the causative agent
of chickenpox and herpes zoster. VZV open reading frame 5 (ORF5) encodes
glycoprotein K (gK), which is conserved among alphaherpesviruses. While VZV gK
has not been characterized, and its role in viral replication is unknown,
homologs of VZV gK in herpes simplex virus type 1 (HSV-1) and pseudorabies virus
(PRV) have been well studied. To identify the VZV ORF5 gene product, we raised a
polyclonal antibody against a fusion protein of ORF5 codons 25 to 122 with
glutathione S-transferase and used it to study the protein in infected cells. A
40,000-molecular-weight protein was detected in cell-free virus by Western
blotting. In immunogold electron microscopic studies, VZV gK was in enveloped
virions and was evenly distributed in the cytoplasm in infected cells. To
determine the function of VZV gK in virus growth, a series of gK deletion mutants
were constructed with VZV cosmid DNA derived from the Oka strain. Full and
partial deletions in gK prevented viral replication when the gK mutant cosmids
were transfected into melanoma cells. Insertion of the HSV-1 (KOS) gK gene into
the endogenous VZV gK site did not compensate for the deletion of VZV gK. The
replacement of VZV gK at a nonnative AvrII site in the VZV genome restored the
phenotypic characteristics of intact recombinant Oka (rOka) virus. Moreover, gK
complementing cells transfected with a full gK deletion mutant exhibited viral
plaques indistinguishable from those of rOka. Our results are consistent with the
studies of gK proteins of HSV-1 and PRV showing that gK is indispensable for
viral replication.
PMID- 10196315
TI - Properties of monoclonal antibodies directed against hepatitis B virus polymerase
protein.
AB - Hepadnavirus polymerases are multifunctional enzymes that play critical roles
during the viral life cycle but have been difficult to study due to a lack of a
well-defined panel of monoclonal antibodies (MAbs). We have used recombinant
human hepatitis B virus (HBV) polymerase (Pol) expressed in and purified from
baculovirus-infected insect cells to generate a panel of six MAbs directed
against HBV Pol protein. Such MAbs were subsequently characterized with respect
to their isotypes and functions in analytical and preparative assays. Using these
MAbs as probes together with various deletion mutants of Pol expressed in insect
cells, we mapped the B-cell epitopes of Pol recognized by these MAbs to amino
acids (aa) 8 to 20 and 20 to 30 in the terminal protein (TP) region of Pol, to aa
225 to 250 in the spacer region, and to aa 800 to 832 in the RNase H domain.
Confocal microscopy and immunocytochemical studies using various Pol-specific
MAbs revealed that the protein itself appears to be exclusively localized to the
cytoplasm. Finally, MAbs specific for the TP domain, but not MAbs specific for
the spacer or RNase H regions of Pol, appeared to inhibit Pol function in the in
vitro priming assay, suggesting that antibody-mediated interference with TP may
now be assessed in the context of HBV replication.
PMID- 10196317
TI - Functional interactions between herpesvirus oncoprotein MEQ and cell cycle
regulator CDK2.
AB - Marek's disease virus, an avian alphaherpesvirus, has been used as an excellent
model to study herpesvirus oncogenesis. One of its potential oncogenes, MEQ, has
been demonstrated to transform a rodent fibroblast cell line, Rat-2, in vitro by
inducing morphological transformation and anchorage- and serum-independent growth
and by protecting cells from apoptosis induced by tumor necrosis factor alpha, C2
ceramide, UV irradiation, or serum deprivation. In this report, we show that
there is a cell cycle-dependent colocalization of MEQ protein and cyclin
dependent kinase 2 (CDK2) in coiled bodies and the nucleolar periphery during the
G1/S boundary and early S phase. To our knowledge, this is the first
demonstration that CDK2 is found to localize to coiled bodies. Such an in vivo
association and possibly subsequent phosphorylation may result in the cytoplasmic
translocation of MEQ protein. Indeed, MEQ is expressed in both the nucleus and
the cytoplasm during the G1/S boundary and early S phase. In addition, we were
able to show in vitro phosphorylation of MEQ by CDKs. We have mapped the CDK
phosphorylation site of MEQ to be serine 42, a residue in the proximity of the
bZIP domain. An indirect-immunofluorescence study of the MEQ S42D mutant, in
which the CDK phosphorylation site was mutated to a charged residue, reveals more
prominent cytoplasmic localization. This lends further support to the notion that
the translocation of MEQ is regulated by phosphorylation. Furthermore,
phosphorylation of MEQ by CDKs drastically reduces the DNA binding activity of
MEQ, which may in part account for the lack of retention of MEQ oncoprotein in
the nucleus. Interestingly, the localization of CDK2 in coiled bodies and the
nucleolar periphery is observed only in MEQ-transformed Rat-2 cells, implicating
MEQ in modifying the subcellular localization of CDK2. Taken together, our data
suggest that there is a novel reciprocal modulation between the herpesvirus
oncoprotein MEQ and CDK2.
PMID- 10196319
TI - The amino-terminal region of Vpr from human immunodeficiency virus type 1 forms
ion channels and kills neurons.
AB - We have previously reported that the accessory protein Vpr from human
immunodeficiency virus type 1 forms cation-selective ion channels in planar lipid
bilayers and is able to depolarize intact cultured neurons by causing an inward
sodium current, resulting in cell death. In this study, we used site-directed
mutagenesis and synthetic peptides to identify the structural regions responsible
for the above functions. Mutations in the N-terminal region of Vpr were found to
affect channel activity, whereas this activity was not affected by mutations in
the hydrophobic region of Vpr (amino acids 53 to 71). Analysis of mutants
containing changes in the basic C terminus confirmed previous results that this
region, although not necessary for ion channel function, was responsible for the
observed rectification of wild-type Vpr currents. A peptide comprising the first
40 N-terminal amino acids of Vpr (N40) was found to be sufficient to form ion
channels similar to those caused by wild-type Vpr in planar lipid bilayers.
Furthermore, N40 was able to cause depolarization of the plasmalemma and cell
death in cultured hippocampal neurons with a time course similar to that seen
with wild-type Vpr, supporting the idea that this region is responsible for Vpr
ion channel function and cytotoxic effects. Since Vpr is found in the serum and
cerebrospinal fluids of AIDS patients, these results may have significance for
AIDS pathology.
PMID- 10196318
TI - CCAAT displacement protein binds to and negatively regulates human papillomavirus
type 6 E6, E7, and E1 promoters.
AB - Expression of human papillomavirus genes increases as the target cell, the
keratinocyte, differentiates. CCAAT displacement protein (CDP) is a cellular
protein which has been shown in other cell types to negatively regulate gene
expression in undifferentiated cells but not in differentiated cells. We have
previously shown that a 66-bp purine-thymidine-rich sequence (the 66-mer) binds
CDP and negatively regulates the human papillomavirus type 6 (HPV-6) E6 promoter
(S. Pattison, D. G. Skalnik, and A. Roman, J. Virol. 71:2013-2022, 1997).
Cotransfection experiments with a plasmid expressing luciferase from the HPV-6
E6, E7, or E1 regulatory region and a plasmid carrying the CDP gene indicate that
CDP represses transcription from all three HPV-6 promoters. Using electrophoretic
mobility shift assays (EMSAs), we have shown that CDP binds HPV-6 both upstream
and downstream of the E6, E7, and E1 transcription initiation start sites.
Furthermore, when keratinocytes were induced to differentiate, all three promoter
activities increased. Consistent with this, immunoblotting and EMSAs revealed
that endogenous nucleus CDP and, correspondingly, DNA binding activity decreased
when keratinocytes were induced to differentiate. The elevated promoter
activities were abrogated by exogenously transfected CDP. Our data demonstrate
that CDP fulfills the requirement of a differentiation-dependent negative
regulator that could tie the HPV life cycle to keratinocyte differentiation.
PMID- 10196320
TI - Assembly of the herpes simplex virus procapsid from purified components and
identification of small complexes containing the major capsid and scaffolding
proteins.
AB - An in vitro system is described for the assembly of herpes simplex virus type 1
(HSV-1) procapsids beginning with three purified components, the major capsid
protein (VP5), the triplexes (VP19C plus VP23), and a hybrid scaffolding protein.
Each component was purified from insect cells expressing the relevant protein(s)
from an appropriate recombinant baculovirus vector. Procapsids formed when the
three purified components were mixed and incubated for 1 h at 37 degrees C.
Procapsids assembled in this way were found to be similar in morphology and in
protein composition to procapsids formed in vitro from cell extracts containing
HSV-1 proteins. When scaffolding and triplex proteins were present in excess in
the purified system, greater than 80% of the major capsid protein was
incorporated into procapsids. Sucrose density gradient ultracentrifugation
studies were carried out to examine the oligomeric state of the purified assembly
components. These analyses showed that (i) VP5 migrated as a monomer at all of
the protein concentrations tested (0.1 to 1 mg/ml), (ii) VP19C and VP23 migrated
together as a complex with the same heterotrimeric composition (VP19C1-VP232) as
virus triplexes, and (iii) the scaffolding protein migrated as a heterogeneous
mixture of oligomers (in the range of monomers to approximately 30-mers) whose
composition was strongly influenced by protein concentration. Similar sucrose
gradient analyses performed with mixtures of VP5 and the scaffolding protein
demonstrated the presence of complexes of the two having molecular weights in the
range of 200,000 to 600,000. The complexes were interpreted to contain one or two
VP5 molecules and up to six scaffolding protein molecules. The results suggest
that procapsid assembly may proceed by addition of the latter complexes to
regions of growing procapsid shell. They indicate further that procapsids can be
formed in vitro from virus-encoded proteins only without any requirement for cell
proteins.
PMID- 10196321
TI - The human immunodeficiency virus type 1 Gag polyprotein has nucleic acid
chaperone activity: possible role in dimerization of genomic RNA and placement of
tRNA on the primer binding site.
AB - The formation of an infectious retrovirus particle requires several RNA-RNA
interaction events. In particular, the genomic RNA molecules form a dimeric
structure, and a cellular tRNA molecule is annealed to an 18-base complementary
region (the primer binding site, or PBS) on the genomic RNA, where it will serve
as primer for reverse transcription. tRNAs normally possess a highly stable
secondary and tertiary structure; it seems unlikely that annealing of a tRNA
molecule to the PBS, which involves unwinding of this structure, could occur
efficiently at physiological temperatures without the assistance of a cofactor.
Many prior studies have shown that the viral nucleocapsid (NC) protein can act as
a nucleic acid chaperone (i.e., facilitate annealing events between nucleic
acids), and the assays used to demonstrate this activity include its ability to
catalyze dimerization of transcripts representing retroviral genomes and the
annealing of tRNA to the PBS in vitro. However, mature NC is not required for
these events in vivo, since protease-deficient viral mutants, in which NC is not
cleaved from the parental Gag polyprotein, are known to contain dimeric RNAs with
tRNA annealed to the PBS. In the present experiments, we have tested recombinant
human immunodeficiency virus type 1 Gag polyprotein for nucleic acid chaperone
activity. The protein was positive by all of our assays, including the ability to
stimulate dimerization and to anneal tRNA to the PBS in vitro. In quantitative
experiments, its activity was approximately equivalent on a molar basis to that
of NC. Based on these results, we suggest that the Gag polyprotein (presumably by
its NC domain) catalyzes the annealing of tRNA to the PBS during (or before)
retrovirus assembly in vivo.
PMID- 10196322
TI - Gag protein epitopes recognized by CD4(+) T-helper lymphocytes from equine
infectious anemia virus-infected carrier horses.
AB - Antigen-specific T-helper (Th) lymphocytes are critical for the development of
antiviral humoral responses and the expansion of cytotoxic T lymphocytes (CTL).
Identification of relevant Th lymphocyte epitopes remains an important step in
the development of an efficacious subunit peptide vaccine against equine
infectious anemia virus (EIAV), a naturally occurring lentivirus of horses. This
study describes Th lymphocyte reactivity in EIAV carrier horses to two proteins,
p26 and p15, encoded by the relatively conserved EIAV gag gene. Using partially
overlapping peptides, multideterminant and possibly promiscuous epitopes were
identified within p26. One peptide was identified which reacted with peripheral
blood mononuclear cells (PBMC) from all five EIAV-infected horses, and three
other peptides were identified which reacted with PBMC from four of five EIAV
infected horses. Four additional peptides containing both CTL and Th lymphocyte
epitopes were also identified. Multiple epitopes were recognized in a region
corresponding to the major homology region of the human immunodeficiency virus, a
region with significant sequence similarity to other lentiviruses including
simian immunodeficiency virus, puma lentivirus, feline immunodeficiency virus,
Jembrana disease virus, visna virus, and caprine arthritis encephalitis virus.
PBMC reactivity to p15 peptides from EIAV carrier horses also occurred. Multiple
p15 peptides were shown to be reactive, but not all infected horses had Th
lymphocytes recognizing p15 epitopes. The identification of peptides reactive
with PBMC from outbred horses, some of which encoded both CTL and Th lymphocyte
epitopes, should contribute to the design of synthetic peptide or recombinant
vector vaccines for EIAV.
PMID- 10196323
TI - Genetic and phenotypic changes accompanying the emergence of epizootic subtype IC
Venezuelan equine encephalitis viruses from an enzootic subtype ID progenitor.
AB - Recent studies have indicated that epizootic Venezuelan equine encephalitis (VEE)
viruses can evolve from enzootic, subtype ID strains that circulate continuously
in lowland tropical forests (A. M. Powers, M. S. Oberste, A. C. Brault, R. Rico
Hesse, S. M. Schmura, J. F. Smith, W. Kang, W. P. Sweeney, and S. C. Weaver, J.
Virol. 71:6697-6705, 1997). To identify mutations associated with the phenotypic
changes leading to epizootics, we sequenced the entire genomes of two subtype IC
epizootic VEE virus strains isolated during a 1992-1993 Venezuelan outbreak and
four sympatric, subtype ID enzootic strains closely related to the predicted
epizootic progenitor. Analysis by maximum-parsimony phylogenetic methods revealed
25 nucleotide differences which were predicted to have accompanied the 1992
epizootic emergence; 7 of these encoded amino acid changes in the nsP1, nsP3,
capsid, and E2 envelope glycoprotein, and 2 were mutations in the 3' untranslated
genome region. Comparisons with the genomic sequences of IAB and other IC
epizootic VEE virus strains revealed that only one of the seven amino acid
changes associated with the 1992 emergence, a threonine-to-methionine change at
position 360 of the nsP3 protein, accompanied another VEE virus emergence event.
Two changes in the E2 envelope glycoprotein region believed to include the major
antigenic determinants, both involving replacement of uncharged residues with
arginine, are also candidates for epizootic determinants.
PMID- 10196324
TI - The cholesterol requirement for sindbis virus entry and exit and characterization
of a spike protein region involved in cholesterol dependence.
AB - Semliki Forest virus (SFV) and Sindbis virus (SIN) are enveloped alphaviruses
that enter cells via low-pH-triggered fusion in the endocytic pathway and exit by
budding from the plasma membrane. Previous studies with cholesterol-depleted
insect cells have shown that SFV requires cholesterol in the cell membrane for
both virus fusion and efficient exit of progeny virus. An SFV mutant, srf-3,
shows efficient fusion and exit in the absence of cholesterol due to a single
point mutation in the E1 spike subunit, proline 226 to serine. We have here
characterized the role of cholesterol in the entry and exit of SIN, an alphavirus
quite distantly related to SFV. Growth, primary infection, fusion, and exit of
SIN were all dramatically inhibited in cholesterol-depleted cells compared to
control cells. Based on sequence differences within the E1 226 region between
SFV, srf-3, and SIN, we constructed six SIN mutants with alterations within this
region and characterized their cholesterol dependence. A SIN mutant, SGM, that
had the srf-3 amino acid sequence from E1 position 224 to 235 showed increases of
approximately 100-fold in infection and approximately 250-fold in fusion with
cholesterol-depleted cells compared with infection and fusion of wild-type SIN.
Pulse-chase analysis demonstrated that SGM exit from cholesterol-depleted cells
was markedly more efficient than that of wild-type SIN. Thus, similar to SFV, SIN
was cholesterol dependent for both virus entry and exit, and the cholesterol
dependence of both steps could be modulated by sequences within the E1 226
region.
PMID- 10196325
TI - Quantitative analysis of the acute and long-term CD4(+) T-cell response to a
persistent gammaherpesvirus.
AB - The murine gammaherpesvirus 68 (MHV-68) replicates in respiratory epithelial
cells, where it establishes a persistent, latent infection limited predominantly
to B lymphocytes. The virus-specific CD4(+) T-cell response in C57BL/6 mice
challenged intranasally with MHV-68 is detected first in the mediastinal lymph
nodes and then in the cervical lymph nodes and the spleen. The numbers of MHV-68
specific CD4(+) T cells generated in congenic mice homozygous for disruption of
the beta2-microglobulin gene tended to be higher, indicating that the absence of
the CD8(+) set in this group resulted in a compensatory response. The peak
frequency within the splenic CD4(+) T-cell population may reach 1:50 in the acute
response; it then drops to 1:400 to 1:500 within 4 months and stays at that level
in the very long term. Sorting for L-selectin (CD62L) expression established that
all virus-specific CD4(+) T cells were initially CD62Llow, with >80% maintaining
that phenotype for the next 14 months. The overall conclusion is that MHV-68
specific CD4(+) T cells remain activated (CD62Llow) and at a stable frequency in
the face of persistent infection.
PMID- 10196326
TI - Intracellular retention of hepatitis B virus surface proteins reduces interleukin
2 augmentation after genetic immunizations.
AB - We have previously shown that hepatitis B virus (HBV) surface antigens (HBsAgs)
are highly immunogenic after genetic immunization. Compared to the secreted
middle HBV surface proteins (MHBs) or small HBV surface proteins (SHBs), the
nonsecreted large HBV surface protein (LHBs), however, induced significantly
weaker humoral and cellular immune responses that could not be augmented by
genetic coimmunizations with cytokine expression plasmids. In order to understand
the mechanisms underlying this phenomenon, we examined the effect of
coimmunizations with an interleukin-2 (IL-2) DNA expression plasmid on the
immunogenicity at the B- and T-cell level of nonsecreted wild-type LHBs, a
secreted mutant LHBs, wild-type SHBs, and a nonsecreted mutant SHBs.
Coimmunizations of mice with plasmids encoding wild-type SHBs or the secreted
mutant LHBs and IL-2 increased anti-HBs responses, helper T-cell proliferative
activity and cytotoxic T-lymphocyte killing. By contrast, coimmunizations of
plasmids encoding wild-type LHBs or nonsecreted mutant SHBs and IL-2 had no
significant effects on immune responses. Interestingly, mice immunized with
cytokine expression plasmids 14 days after the injection of the wild-type LHBs
plasmid showed augmented immune responses compared to animals simultaneously
injected with both expression constructs. Anti-HBs responses in mice injected
with plasmids encoding secreted forms of HBsAgs were detectable about 10 days
earlier than those in mice immunized with plasmids encoding nonsecreted forms of
HBsAgs. Based on these observations, we conclude that cytokines produced by DNA
plasmids at the initial site of antigen presentation cannot augment LHBs specific
immune responses because LHBs is not produced at high enough levels or is not
accessible for uptake by antigen-presenting cells.
PMID- 10196327
TI - Adeno-associated virus (AAV) type 5 Rep protein cleaves a unique terminal
resolution site compared with other AAV serotypes.
AB - Adeno-associated virus (AAV) replication depends on two viral components for
replication: the AAV nonstructural proteins (Rep) in trans, and inverted terminal
repeat (ITR) sequences in cis. AAV type 5 (AAV5) is a distinct virus compared to
the other cloned AAV serotypes. Whereas the Rep proteins and ITRs of other
serotypes are interchangeable and can be used to produce recombinant viral
particles of a different serotype, AAV5 Rep proteins cannot cross-complement in
the packaging of a genome with an AAV2 ITR. In vitro replication assays indicated
that the block occurs at the level of replication instead of at viral assembly.
AAV2 and AAV5 Rep binding activities demonstrate similar affinities for either an
AAV2 or AAV5 ITR; however, comparison of terminal resolution site (TRS)
endonuclease activities showed a difference in specificity for the two DNA
sequences. AAV2 Rep78 cleaved only a type 2 ITR DNA sequence, and AAV5 Rep78
cleaved only a type 5 probe efficiently. Mapping of the AAV5 ITR TRS identified a
distinct cleavage site (AGTG TGGC) which is absent from the ITRs of other AAV
serotypes. Comparison of the TRSs in the AAV2 ITR, the AAV5 ITR, and the AAV
chromosome 19 integration locus identified some conserved nucleotides downstream
of the cleavage site but little homology upstream.
PMID- 10196328
TI - Disruption of nucleotide excision repair by the human T-cell leukemia virus type
1 Tax protein.
AB - The Tax protein of human T-cell leukemia virus type 1 (HTLV-1) is a
transcriptional transactivator and viral oncogene. Since cellular transformation
has been frequently linked to alterations in genome stability, we investigated
the effect of Tax on nucleotide excision repair (NER), a prominent cellular DNA
repair pathway. Cells expressing Tax exhibited a reduced capacity for NER as
measured by unscheduled DNA synthesis and host cell reactivation assays. The
cellular proliferating cell nuclear antigen (PCNA) gene product regulates DNA
replication and repair pathways, including NER. Since Tax activates transcription
of the PCNA promoter, we investigated whether this activity contributes to the
reduction of NER. Tax increased endogenous PCNA protein expression, and analysis
of Tax mutant proteins demonstrated that the reduction in NER correlated with Tax
transactivation of PCNA gene expression. Direct overexpression of PCNA also
reduced NER. We propose that overexpression of PCNA, and disruption of NER
induced by Tax, predisposes cells to accumulate DNA damage and contributes to
HTLV-1 transformation.
PMID- 10196329
TI - Functional anatomy of herpes simplex virus 1 overlapping genes encoding infected
cell protein 22 and US1.5 protein.
AB - Earlier studies have shown that (i) the coding domain of the alpha22 gene encodes
two proteins, the 420-amino-acid infected-cell protein 22 (ICP22) and a protein,
US1.5, which is initiated from methionine 147 of ICP22 and which is colinear with
the remaining portion of that protein; (ii) posttranslational processing of ICP22
mediated largely by the viral protein kinase UL13 yields several isoforms
differing in electrophoretic mobility; and (iii) mutants lacking the carboxyl
terminal half of the ICP22 and therefore DeltaUS1.5 are avirulent and fail to
express normal levels of subsets of both alpha (e.g., ICP0) or gamma2 (e.g., US11
and UL38) proteins. We have generated and analyzed two sets of recombinant
viruses. The first lacked portions of or all of the sequences expressed solely by
ICP22. The second set lacked 10 to 40 3'-terminal codons of ICP22 and US1. 5. The
results were as follows. (i) In cells infected with mutants lacking amino
terminal sequences, translation initiation begins at methionine 147. The
resulting protein cannot be differentiated in mobility from authentic US1.5, and
its posttranslational processing is mediated by the UL13 protein kinase. (ii)
Expression of US11 and UL38 genes by mutants carrying only the US1.5 gene is
similar to that of wild-type parent virus. (iii) Mutants which express only US1.
5 protein are avirulent in mice. (iv) The coding sequences Met147 to Met171 are
essential for posttranslational processing of the US1.5 protein. (v) ICP22 made
by mutants lacking 15 or fewer of the 3'-terminal codons are posttranslationally
processed whereas those lacking 18 or more codons are not processed. (vi) Wild
type and mutant ICP22 proteins localized in both nucleus and cytoplasm
irrespective of posttranslational processing. We conclude that ICP22 encodes two
sets of functions, one in the amino terminus unique to ICP22 and one shared by
ICP22 and US1.5. These functions are required for viral replication in
experimental animals. US1.5 protein must be posttranslationally modified by the
UL13 protein kinase to enable expression of a subset of late genes exemplified by
UL38 and US11. Posttranslational processing is determined by two sets of
sequences, at the amino terminus and at the carboxyl terminus of US1.5,
respectively, a finding consistent with the hypothesis that both domains interact
with protein partners for specific functions.
PMID- 10196330
TI - Genetic and fitness changes accompanying adaptation of an arbovirus to vertebrate
and invertebrate cells.
AB - The alternating host cycle and persistent vector infection may constrain the
evolution of arboviruses. To test this hypothesis, eastern equine encephalitis
virus was passaged in BHK or mosquito cells, as well as in alternating (both)
host cell passages. High and low multiplicities were used to examine the effect
of defective interfering particles. Clonal BHK and persistent mosquito cell
infections were also evaluated. Fitness was measured with one-step growth curves
and competition assays, and mutations were evaluated by nucleotide sequencing and
RNA fingerprinting. All passages and assays were done at 32 degrees C to
eliminate temperature as a selection factor. Viruses passaged in either cell type
alone exhibited fitness declines in the bypassed cells, while high-multiplicity
and clonal passages caused fitness declines in both types of cells. Bypassed cell
fitness losses were mosquito and vertebrate specific and were not restricted to
individual cell lines. Fitness increases occurred in the cell line used for
single-host-adaptation passages and in both cells for alternately passaged
viruses. Surprisingly, single-host-cell passage increased fitness in that cell
type no more than alternating passages. However, single-host-cell adaptation
resulted in more mutations than alternating cell passages. Mosquito cell
adaptation invariably resulted in replacement of the stop codon in nsP3 with
arginine or cysteine. In one case, BHK cell adaptation resulted in a 238
nucleotide deletion in the 3' untranslated region. Many nonsynonymous
substitutions were shared among more than one BHK or mosquito cell passage
series, suggesting positive Darwinian selection. Our results suggest that
alternating host transmission cycles constrain the evolutionary rates of
arboviruses but not their fitness for either host alone.
PMID- 10196331
TI - Structures of endogenous nonecotropic murine leukemia virus (MLV) long terminal
repeats in wild mice: implication for evolution of MLVs.
AB - To develop a better understanding of the interaction between retroviruses and
their hosts, we have investigated the polymorphism in endogenous murine leukemia
proviruses (MLVs). We used genomic libraries of wild mouse DNAs and PCR to
analyze genetic variation in the proviruses found in wild mouse species,
including Mus musculus (M. m. castaneus, M. m. musculus, M. m. molossinus, and M.
m. domesticus), Mus spretus, and Mus spicelegus, as well as some inbred
laboratory strains. In this analysis, we detected several unique forms of
sequence organization in the U3 regions of the long terminal repeats of these
proviruses. The distribution of the proviruses with unique U3 structures
demonstrated that xenotropic MLV-related proviruses were present only in M.
musculus subspecies, while polytropic MLV-related proviruses were found in both
M. musculus and M. spretus. Furthermore, one unique provirus from M. spicelegus
was found to be equidistant from ecotropic provirus and nonecotropic provirus by
phylogenetic analysis. This provirus, termed HEMV, was thus likely to be related
to the common ancestor of these MLVs. Moreover, an ancestral type of polytropic
MLV-related provirus was detected in M. spretus species. Despite their
"ancestral" phylogenetic position, proviruses of these types are not widespread
in mice, implying more-recent spread by infection rather than inheritance. These
results imply that recent evolution of these proviruses involved alternating
periods of replication as virus and residence in the germ line.
PMID- 10196332
TI - Polyvalent Rev decoys act as artificial Rev-responsive elements.
AB - Interactions between Rev and the Rev-responsive element (RRE) control the order,
rate, and extent of gene expression in human immunodeficiency virus type 1. Rev
decoys may therefore prove to be useful RNA therapeutics for the treatment of
AIDS. To improve upon the current generation of Rev decoys that bind single Rev
molecules, it would be useful to generate polyvalent Rev decoys that could bind
multiple Rev molecules. J. Kjems and P. A. Sharp (J. Virol. 67:4769-4776, 1993)
originally constructed functional polyvalent Rev decoys, but the structural
context of these polyvalent decoys remains unclear, and it has been argued that
the individual decoys were either structurally discrete (Kjems and Sharp, J.
Virol. 67:4769-4776, 1993) or were part of an extended helix (R. W. Zemmel et
al., Mol. Biol. 258:763-777, 1996). To resolve the differences between these
models, we have designed and synthesized concatemers of Rev-binding elements
(RBEs) that fold to form multiple, discrete, high-affinity Rev-binding sites. We
find that the concatenated RBEs can facilitate the cytoplasmic transport of viral
mRNAs and therefore likely bind multiple Rev molecules. These artificial RREs may
simultaneously sequester Rev and hinder access to the cellular transport
machinery.
PMID- 10196333
TI - Retrograde, transneuronal spread of pseudorabies virus in defined neuronal
circuitry of the rat brain is facilitated by gE mutations that reduce virulence.
AB - The pseudorabies virus (PRV) gE gene encodes a multifunctional membrane protein
found in infected cell membranes and in the virion envelope. Deletion of the gE
gene results in marked attenuation of the virus in almost every animal species
tested that is permissive for PRV. A common inference is that gE mutants are less
virulent because they have reduced ability to spread from cell to cell; e.g., gE
mutants infect fewer cells and, accordingly, animals live longer. In this report,
we demonstrate that this inference does not hold in a rat experimental model for
virus invasion of the brain. We find that animals infected with gE mutants live
longer despite extensive retrograde, transneuronal spread of virus in the rat
brain. In this model of brain infection, virus is injected into the stomach
musculature and virions spread to the brain in long axons of brain stem neurons
that give rise to the tenth cranial nerve (the vagus). The infection then spreads
from neuron to neuron in well-defined, and physically separated, areas of the
brain involved in autonomic regulation of the viscera. We examined the
progression of infection of five PRV strains in this circuitry: the wild-type PRV
Becker strain, the attenuated PRV-Bartha vaccine strain, and three gE mutants
isogenic with the PRV-Becker strain. By 60 to 67 h after infection, all PRV
Becker-infected animals were dead. Analysis of Becker-infected rats killed prior
to virus-induced death demonstrated that the virus had established an infection
only in the primary vagal neurons connected directly to the stomach and
synaptically linked neurons in the immediate vicinity of the caudal brain stem.
There was little spread to other neurons in the vagus circuitry. In contrast,
rats infected with PRV-Bartha or PRV-Becker gE mutants survived to at least 96 h
and exhibited few overt signs of disease. Despite this long survival and the lack
of symptoms, brains of animals sacrificed at this time revealed extensive
transsynaptic infection not only of the brain stem but also of areas of the
forebrain synaptically linked to neurons in the brain stem. This finding provides
evidence that the gE protein plays a role in promoting symptoms of infection and
death in animals that is independent of neuron-to-neuron spread during brain
infection. When this early virulence function is not active, animals live longer,
resulting in more extensive spread of virus in the brain.
PMID- 10196334
TI - Cyanovirin-N binds to gp120 to interfere with CD4-dependent human
immunodeficiency virus type 1 virion binding, fusion, and infectivity but does
not affect the CD4 binding site on gp120 or soluble CD4-induced conformational
changes in gp120.
AB - Cyanovirin-N (CV-N), an 11-kDa protein isolated from the cyanobacterium Nostoc
ellipsosporum, potently inactivates diverse strains of human immunodeficiency
virus type 1 (HIV-1), HIV-2, and simian immunodeficiency virus. While it has been
well established that the viral surface envelope glycoprotein gp120 is a
molecular target of CV-N, the detailed mechanism of action is of further
interest. We compared matched native and CV-N-treated virus preparations in a
panel of assays that measure viral replication, assessing successive stages of
the viral life cycle. CV-N-treated virions failed to infect cells as detected by
p24 production and quantitative PCR for HIV-1 reverse transcription products,
whereas treatment of the target cells did not block infection, confirming that CV
N acts at the level of the virus, not the target cell, to abort the initial
infection process. Compared to native HIV-1 preparations, CV-N-treated HIV-1
virions showed impaired CD4-dependent binding to CD4(+) T cells and did not
mediate "fusion from without" of CD4(+) target cells. CV-N also blocked HIV
envelope glycoprotein Env-induced, CD4-dependent cell-cell fusion. Mapping
studies with monoclonal antibodies (MAbs) to defined epitopes on the HIV-1
envelope glycoprotein indicated that CV-N binds to gp120 in a manner that does
not occlude or alter the CD4 binding site or V3 loop or other domains on gp120
recognized by defined MAbs and does not interfere with soluble CD4-induced
conformational changes in gp120. Binding of CV-N to soluble gp120 or virions
inhibited subsequent binding of the unique neutralizing MAb 2G12, which
recognizes a glycosylation-dependent epitope. However, prior binding of 2G12 MAb
to gp120 did not block subsequent binding by CV-N. These results help clarify the
mechanism of action of CV-N and suggest that the compound may act in part by
preventing essential interactions between the envelope glycoprotein and target
cell receptors. This proposed mechanism is consistent with the extensive activity
profile of CV-N against numerous isolates of HIV-1 and other lentiviruses and
supports the potential broad utility of this protein as a microbicide to prevent
the sexual transmission of HIV.
PMID- 10196335
TI - Intracellular trafficking and localization of the pseudorabies virus Us9 type II
envelope protein to host and viral membranes.
AB - The Us9 protein is a phosphorylated membrane protein present in the lipid
envelope of pseudorabies virus (PRV) particles in a unique tail-anchored type II
membrane topology. In this report, we demonstrate that the steady-state residence
of the Us9 protein is in a cellular compartment in or near the trans-Golgi
network (TGN). Through internalization assays with an enhanced green fluorescent
protein epitope-tagged Us9 protein, we demonstrate that the maintenance of Us9 to
the TGN region is a dynamic process involving retrieval of molecules from the
cell surface. Deletion analysis of the cytoplasmic tail reveals that an acidic
cluster containing putative phosphorylation sites is necessary for the recycling
of Us9 from the plasma membrane. The absence of this cluster results in the
relocalization of Us9 to the plasma membrane due to a defect in endocytosis. The
acidic motif, however, does not contain signals needed to direct the
incorporation of Us9 into viral envelopes. In this study, we also investigate the
role of a dileucine endocytosis signal in the Us9 cytoplasmic tail in the
recycling and retention of Us9 to the TGN region. Site-directed mutagenesis of
the dileucine motif results in an increase in Us9 plasma membrane staining and a
partial internalization defect.
PMID- 10196336
TI - Mapping EBNA-1 domains involved in binding to metaphase chromosomes.
AB - The Epstein-Barr virus (EBV) genome can persist in dividing human B cells as
multicopy circular episomes. Viral episomes replicate in synchrony with host cell
DNA and are maintained at a relatively constant copy number for a long time. Only
two viral elements, the replication origin OriP and the EBNA-1 protein, are
required for the persistence of viral genomes during latency. EBNA-1 activates
OriP during the S phase and may also contribute to the partition and/or retention
of viral genomes during mitosis. Indeed, EBNA-1 has been shown to interact with
mitotic chromatin. Moreover, viral genomes are noncovalently associated with
metaphase chromosomes. This suggests that EBNA-1 may facilitate the anchorage of
viral genomes on cellular chromosomes, thus ensuring proper partition and
retention. In the present paper, we have investigated the chromosome-binding
activity of EBV EBNA-1, herpesvirus papio (HVP) EBNA-1, and various derivatives
of EBV EBNA-1, fused to a variant of the green fluorescent protein. The results
show that binding to metaphase chromosomes is a common property of EBV and HVP
EBNA-1. Further studies indicated that at least three independent domains (CBS-1,
-2, and -3) mediate EBNA-1 binding to metaphase chromosomes. In agreement with
the anchorage model, two of these domains mapped to a region that has been
previously demonstrated to be required for the long-term persistence of OriP
containing plasmids.
PMID- 10196338
TI - Long-term episomal maintenance of bovine papillomavirus type 1 plasmids is
determined by attachment to host chromosomes, which Is mediated by the viral E2
protein and its binding sites.
AB - Papillomavirus genomes are stably maintained as extrachromosomal nuclear plasmids
in dividing host cells. To address the mechanisms responsible for stable
maintenance of virus, we examined nuclear compartmentalization of plasmids
containing the full-length upstream regulatory region (URR) from the bovine
papillomavirus type 1 (BPV1) genome. We found that these plasmids are tightly
associated with the nuclear chromatin both in the stable cell lines that maintain
episomal copies of the plasmids and in transiently transfected cells expressing
the viral E1 and E2 proteins. Further analysis of viral factors revealed that the
E2 protein in trans and its multiple binding sites in cis are both necessary and
sufficient for the chromatin attachment of the plasmids. On the other hand, the
BPV1 URR-dependent plasmid replication and chromatin attachment processes are
clearly independent of each other. The ability of the plasmids to stably maintain
episomes correlates clearly with their chromatin association function. These data
suggest that viral E2 protein-mediated attachment of BPV1 genomes to the host
cell chromatin could provide a mechanism for the coupling of viral genome
multiplication and partitioning to the host cell cycle during viral latent
infection.
PMID- 10196337
TI - Subtypes of human immunodeficiency virus type 1 and disease stage among women in
Nairobi, Kenya.
AB - In sub-Saharan Africa, where the effects of human immunodeficiency virus type 1
(HIV-1) have been most devastating, there are multiple subtypes of this virus.
The distribution of different subtypes within African populations is generally
not linked to particular risk behaviors. Thus, Africa is an ideal setting in
which to examine the diversity and mixing of viruses from different subtypes on a
population basis. In this setting, it is also possible to address whether
infection with a particular subtype is associated with differences in disease
stage. To address these questions, we analyzed the HIV-1 subtype, plasma viral
loads, and CD4 lymphocyte levels in 320 women from Nairobi, Kenya. Subtype was
determined by a combination of heteroduplex mobility assays and sequence analyses
of envelope genes, using geographically diverse subtype reference sequences as
well as envelope sequences of known subtype from Kenya. The distribution of
subtypes in this population was as follows: subtype A, 225 (70.3%); subtype D, 65
(20.5%); subtype C, 22 (6.9%); and subtype G, 1 (0.3%). Intersubtype recombinant
envelope genes were detected in 2.2% of the sequences analyzed. Given that the
sequences analyzed represented only a small fraction of the proviral genome, this
suggests that intersubtype recombinant viral genomes may be very common in Kenya
and in other parts of Africa where there are multiple subtypes. The plasma viral
RNA levels were highest in women infected with subtype C virus, and women
infected with subtype C virus had significantly lower CD4 lymphocyte levels than
women infected with the other subtypes. Together, these data suggest that women
in Kenya who are infected with subtype C viruses are at more advanced stages of
immunosuppression than women infected with subtype A or D. There are at least two
models to explain the data from this cross-sectional study; one is that infection
with subtype C is associated with a more rapid disease progression, and the
second is that subtype C represents an older epidemic in Kenya. Discriminating
between these possibilities in a longitudinal study will be important for
increasing our understanding of the role of specific subtypes in the transmission
and pathogenesis of HIV-1.
PMID- 10196339
TI - Comparative analysis of evolutionary mechanisms of the hemagglutinin and three
internal protein genes of influenza B virus: multiple cocirculating lineages and
frequent reassortment of the NP, M, and NS genes.
AB - Phylogenetic profiles of the genes coding for the hemagglutinin (HA) protein,
nucleoprotein (NP), matrix (M) protein, and nonstructural (NS) proteins of
influenza B viruses isolated from 1940 to 1998 were analyzed in a parallel manner
in order to understand the evolutionary mechanisms of these viruses. Unlike human
influenza A (H3N2) viruses, the evolutionary pathways of all four genes of recent
influenza B viruses revealed similar patterns of genetic divergence into two
major lineages. Although evolutionary rates of the HA, NP, M, and NS genes of
influenza B viruses were estimated to be generally lower than those of human
influenza A viruses, genes of influenza B viruses demonstrated complex
phylogenetic patterns, indicating alternative mechanisms for generation of virus
variability. Topologies of the evolutionary trees of each gene were determined to
be quite distinct from one another, showing that these genes were evolving in an
independent manner. Furthermore, variable topologies were apparently the result
of frequent genetic exchange among cocirculating epidemic viruses. Evolutionary
analysis done in the present study provided further evidence for cocirculation of
multiple lineages as well as sequestering and reemergence of phylogenetic
lineages of the internal genes. In addition, comparison of deduced amino acid
sequences revealed a novel amino acid deletion in the HA1 domain of the HA
protein of recent isolates from 1998 belonging to the B/Yamagata/16/88-like
lineage. It thus became apparent that, despite lower evolutionary rates,
influenza B viruses were able to generate genetic diversity among circulating
viruses through a combination of evolutionary mechanisms involving cocirculating
lineages and genetic reassortment by which new variants with distinct gene
constellations emerged.
PMID- 10196340
TI - Molecular cloning and phylogenetic analysis of human immunodeficiency virus type
1 subtype C: a set of 23 full-length clones from Botswana.
AB - To better understand the virological aspect of the expanding AIDS epidemic in
southern Africa, a set of 23 near-full-length clones of human immunodeficiency
virus type 1 (HIV-1) representing eight AIDS patients from Botswana were
sequenced and analyzed phylogenetically. All study viruses from Botswana belonged
to HIV-1 subtype C. The interpatient diversity of the clones from Botswana was
higher than among full-length isolates of subtype B or among a set of full-length
HIV-1 genomes of subtype C from India (mean value of 9. 1% versus 6.5 and 4.3%,
respectively; P < 0.0001 for both comparisons). Similar results were observed in
all genes across the entire viral genome. We suggest that the high level of HIV-1
diversity might be a typical feature of the subtype C epidemic in southern
Africa. The reason or reasons for this diversity are unclear, but may include an
altered replication efficiency of HIV-1 subtype C and/or the multiple
introduction of different subtype C viruses.
PMID- 10196341
TI - Subdomain folding and biological activity of the core structure from human
immunodeficiency virus type 1 gp41: implications for viral membrane fusion.
AB - The envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1) consists
of two subunits, gp120 and gp41. The extraviral portion (ectodomain) of gp41
contains an alpha-helical domain that likely represents the core of the fusion
active conformation of the molecule. Here we report the identification and
characterization of a minimal, autonomous folding subdomain that retains key
determinants in specifying the overall fold of the gp41 ectodomain core. This
subdomain, designated N34(L6)C28, is formed by covalent attachment of peptides N
34 and C-28 by a short flexible linker in place of the normal disulfide-bonded
loop sequence. N34(L6)C28 forms a highly thermostable, alpha-helical trimer.
Point mutations within the envelope protein complex that abolish membrane fusion
and HIV-1 infectivity also impede the formation of the N34(L6)C28 core. Moreover,
N34(L6)C28 is capable of inhibiting HIV-1 envelope-mediated membrane fusion.
Taken together, these results indicate that the N34(L6)C28 core plays a direct
role in the membrane fusion step of HIV-1 infection and thus provides a molecular
target for the development of antiviral pharmaceutical agents.
PMID- 10196343
TI - Immunization with a live, attenuated simian immunodeficiency virus vaccine leads
to restriction of viral diversity in Rhesus macaques not protected from
pathogenic challenge.
AB - Rhesus macaques immunized with simian immunodeficiency virus SIVmac239Deltanef
but not protected from SIVmac251 challenge were studied to determine the genetic
and biological characteristics of the breakthrough viruses. Assessment of SIV
genetic diversity (env V1-V2) revealed a reduction in the number of viral species
in the immunized, unprotected macaques, compared to the number in nonimmunized
controls. However, no evidence for selection of a specific V1-V2 genotype was
observed, and biologically cloned isolates from the animals with breakthrough
virus were similar with respect to replication kinetics and coreceptor use in
vitro.
PMID- 10196342
TI - Oncogene activation in myeloid leukemias by Graffi murine leukemia virus proviral
integration.
AB - The Graffi murine leukemia virus (MuLV) is a nondefective retrovirus that induces
granulocytic leukemia in BALB/c and NFS mice. To identify genes involved in
Graffi MuLV-induced granulocytic leukemia, tumor cell DNAs were examined for
genetic alterations at loci described as common proviral integration sites in
MuLV-induced myeloid, lymphoid, and erythroid leukemias. Southern blot analysis
revealed rearrangements in c-myc, Fli-1, Pim-1, and Spi-1/PU.1 genes in 20, 10,
3.3, and 3.3% of the tumors tested, respectively. These results demonstrate for
the first time the involvement of those genes in granulocytic leukemia.
PMID- 10196344
TI - Type 1 CD4(+) T-cell help is required for induction of antipeptide multispecific
cytotoxic T lymphocytes by a lipopeptidic vaccine in rhesus macaques.
AB - We have optimized the induction of antiviral cytotoxic T lymphocytes (CTL) in
rhesus macaques by a lipopeptide vaccine containing seven peptides from simian
immunodeficiency virus (SIV) Nef and Gag proteins and a strong T-helper peptide
from tetanus toxoid (TT) that is promiscuous in humans (peptide TT 830-846). Two
of the eight immunized macaques showed T-helper (Th) cell proliferation and a
specific synthesis of gamma interferon in response to TT 830-846 peptide. They
also showed multispecific cytotoxic activity against three to five of the
immunizing SIV peptides. These results show the importance of a strong specific
type 1 Th response for inducing a multispecific CTL response in vivo, which is
essential for the development of an anti-human immunodeficiency virus vaccine.
PMID- 10196345
TI - Immunization with potato plants expressing VP60 protein protects against rabbit
hemorrhagic disease virus.
AB - The major structural protein VP60 of rabbit hemorrhagic disease virus (RHDV) has
been produced in transgenic potato plants under the control of a cauliflower
mosaic virus 35S promoter or a modified 35S promoter that included two copies of
a strong transcriptional enhancer. Both types of promoters allowed the production
of specific mRNAs and detectable levels of recombinant VP60, which were higher
for the constructs carrying the modified 35S promoter. Rabbits immunized with
leaf extracts from plants carrying this modified 35S promoter showed high anti
VP60 antibody titers and were fully protected against the hemorrhagic disease.
PMID- 10196346
TI - Cellular elongation factor 1delta is modified in cells infected with
representative alpha-, beta-, or gammaherpesviruses.
AB - Earlier reports (Y. Kawaguchi, R. Bruni, and B. Roizman, J. Virol. 71:1019-1024,
1997; Y. Kawaguchi, C. Van Sant, and B. Roizman, J. Virol. 72:1731-1736, 1998)
showed that herpes simplex virus 1 (HSV-1) infection causes the
hyperphosphorylation of translation elongation factor 1delta (EF-1delta) and that
the modification of EF-1delta is the consequence of direct phosphorylation by a
viral protein kinase encoded by the UL13 gene of HSV-1. The UL13 gene is
conserved in members of all herpesvirus subfamilies. Here we report the
following. (i) In various mammalian cells, accumulation of the
hyperphosphorylated form of EF-1delta is observed after infection with alpha-,
beta-, and gammaherpesviruses, including HSV-2, feline herpesvirus 1,
pseudorabiesvirus, bovine herpesvirus 1, human cytomegalovirus (HCMV), and equine
herpesvirus 2. (ii) In human lung fibroblast cells infected with recombinant HSV
1 lacking the UL13 gene, the hypophosphorylated form of EF-1delta is a minor
species, whereas the amount of the hyperphosphorylated form of EF-1delta
significantly increases in cells infected with the recombinant HSV-1 in which
UL13 had been replaced by HCMV UL97, a homologue of UL13. These results indicate
that the posttranslational modification of EF-1delta is conserved herpesvirus
function and the UL13 homologues may be responsible for the universal
modification of the translation factor.
PMID- 10196347
TI - Contribution of virus-receptor interaction to distinct viral proliferation of
neuropathogenic and nonneuropathogenic murine leukemia viruses in rat glial
cells.
AB - The efficiency of receptor-mediated entry of pseudotyped virus carrying the
surface protein (SU) of clone A8, a neuropathogenic variant of Friend murine
leukemia virus (FrMLV), to rat glial cell line F10 was 1 order of magnitude
greater than that of pseudotyped virus carrying SU of nonneuropathogenic FrMLV
clone 57. Introduction of the gene coding for ecotropic MLV receptor on F10 cells
(F10-ecoR) into SIRC cells, which are naturally resistant to FrMLV infection,
also revealed the difference in receptor recognition between the A8 and the 57
viruses. Our results show that the difference in receptor utilization between A8
SU and 57-SU only partially explains the 3-order-of-magnitude difference in
proliferation between A8 and 57 viruses in F10 cells.
PMID- 10196348
TI - Molecular cloning and expression of major structural protein VP1 of the human
polyomavirus JC virus: formation of virus-like particles useful for immunological
and therapeutic studies.
AB - The major structural viral protein, VP1, of the human polyomavirus JC virus
(JCV), the causative agent of progressive multifocal leukoencephalopathy (PML),
was expressed by using recombinant baculoviruses. Recombinant VP1 formed virus
like particles (VLP) with the typical morphology of empty JCV capsids. Purified
VP1 VLP bind to SVG, B, and T cells, as well as to monkey kidney cells. After
binding, VP1 VLP were also internalized with high efficiency and transported to
the nucleus. Immunization studies revealed these particles as highly immunogenic
when administered with adjuvant, while immunization without adjuvant induced no
immune response. VP1 VLP hyperimmune serum inhibits binding to SVG cells and
neutralizes natural JCV. Furthermore, the potential of VP1 VLP as an efficient
transporter system for gene therapy was demonstrated. Exogenous DNA could be
efficiently packaged into VP1 VLP, and the packaged DNA was transferred into COS
7 cells as shown by the expression of a marker gene. Thus, VP1 VLP are useful for
PML vaccine development and represent a potential new transporter system for
human gene therapy.
PMID- 10196349
TI - A sodium-dependent neutral-amino-acid transporter mediates infections of feline
and baboon endogenous retroviruses and simian type D retroviruses.
AB - The type D simian retroviruses cause immunosuppression in macaques and have been
reported as a presumptive opportunistic infection in a patient with AIDS.
Previous evidence based on viral interference has strongly suggested that the
type D simian viruses share a common but unknown cell surface receptor with three
type C viruses: feline endogenous virus (RD114), baboon endogenous virus, and
avian reticuloendotheliosis virus. Furthermore, the receptor gene for these
viruses has been mapped to human chromosome 19q13.1-13.2. We now report the
isolation and characterization of a cell surface receptor for this group of
retroviruses by using a human T-lymphocyte cDNA library in a retroviral vector.
Swiss mouse fibroblasts (NIH 3T3), which are naturally resistant to RD114, were
transduced with the retroviral library and then challenged with an RD114
pseudotyped virus containing a dominant selectable gene for puromycin resistance.
Puromycin selection yielded 12 cellular clones that were highly susceptible to a
beta-galactosidase-encoding lacZ(RD114) pseudotype virus. Using PCR primers
specific for vector sequences, we amplified a common 2.9-kb product from 10
positive clones. Expression of the 2.9-kb cDNA in Chinese hamster ovary cells
conferred susceptibility to RD114, baboon endogenous virus, and the type D simian
retroviruses. The 2.9-kb cDNA predicted a protein of 541 amino acids that had 98%
identity with the previously cloned human Na+-dependent neutral-amino-acid
transporter Bo. Accordingly, expression of the RD114 receptor in NIH 3T3 cells
resulted in enhanced cellular uptake of L-[3H]alanine and L-[3H]glutamine. RNA
blot (Northern) analysis suggested that the RD114 receptor is widely expressed in
human tissues and cell lines, including hematopoietic cells. The human Bo
transporter gene has been previously mapped to 19q13.3, which is closely linked
to the gene locus of the RD114 receptor.
PMID- 10196350
TI - Monoclonal antibodies against the minimal DNA-binding domain in the carboxyl
terminal region of human immunodeficiency virus type 1 integrase.
AB - Integrase of human immunodeficiency virus type 1 (HIVIN) consists of 288 amino
acids, and its minimum DNA-binding domain (MDBD) (amino acids [aa] 220 to 270) is
required for the integration reaction. We produced and characterized four murine
monoclonal antibodies (MAbs) to the MDBD of HIVIN (strain LAI). Immunoblot and
enzyme-linked immunosorbent assays with truncated HIVINs showed that those MAbs
recognized sequential epitopes within the MDBD (aa 228 to 236, 237 to 252, 253 to
261, and 262 to 270). Their binding to HIVIN inhibited terminal cleavage and
strand transfer activities but not disintegration activity in vitro. This
collection of MAbs is useful for studying the structure and function of the MDBD
by complementing mutational analyses and other biochemical studies.
PMID- 10196351
TI - The proto-oncogene c-myc is a direct target gene of Epstein-Barr virus nuclear
antigen 2.
AB - Epstein-Barr virus (EBV) infects and transforms primary B lymphocytes in vitro.
Viral infection initiates the cell cycle entry of the resting B lymphocytes. The
maintenance of proliferation in the infected cells is strictly dependent on
functional EBNA2. We have recently developed a conditional immortalization system
for EBV by rendering the function of EBNA2, and thus proliferation of the
immortalized cells, dependent on estrogen. This cellular system was used to
identify early events preceding induction of proliferation. We show that LMP1 and
c-myc are directly activated by EBNA2, indicating that all cellular factors
essential for induction of these genes by EBNA2 are present in the resting cells.
In contrast, induction of the cell cycle regulators cyclin D2 and cdk4 are
secondary events, which require de novo protein synthesis.
PMID- 10196352
TI - The role of Pr55(gag) in the annealing of tRNA3Lys to human immunodeficiency
virus type 1 genomic RNA.
AB - During human immunodeficiency virus type 1 (HIV-1) assembly, the primer tRNA for
the reverse transcriptase-catalyzed synthesis of minus-strand strong-stop cDNA,
tRNA3Lys, is selectively packaged into the virus and annealed onto the primer
binding site on the RNA genome. Annealing of tRNA3Lys in HIV-1 is independent of
polyprotein processing and is facilitated in vitro by p7 nucleocapsid (NCp7). We
have previously shown that mutations in clusters of basic amino acids flanking
the first Cys-His box in NC sequence inhibit annealing of tRNA3Lys in vivo by 70
to 80%. In this report, we have investigated whether these NC mutations act
through Pr55(gag) or Pr160(gag-pol). In vivo placement of tRNA3Lys is measured
with total viral RNA as the source of primer tRNA-template in an in vitro reverse
transcription assay. Cotransfection of COS cells with a plasmid coding for either
mutant Pr55(gag) or mutant Pr160(gag-pol), and with a plasmid containing HIV-1
proviral DNA, shows that only the NC mutations in Pr55(gag) inhibit tRNA3Lys
placement. The NC mutations in Pr55(gag) reduce viral infectivity by 95% and are
trans-dominant-negative, i.e., they inhibit genomic placement of tRNA3Lys even in
the presence of wild-type Pr55(gag). This dominant phenotype may indicate that
the mutant Pr55(gag) is disrupting an ordered Pr55(gag) structure responsible for
the annealing of tRNA3Lys to genomic RNA.
PMID- 10196353
TI - Novel role for E4 region genes in protection of adenovirus vectors from lysis by
cytotoxic T lymphocytes.
AB - Target cells infected with adenovirus (Ad) vectors containing intact E3 and E4
regions were found to be relatively resistant to lysis by Ad-specific cytotoxic T
lymphocytes. Elements from both the E3 and the E4 regions were required for this
effect, leading to the identification of a previously undescribed role for E4
gene products in resistance to cytolysis.
PMID- 10196354
TI - The murine homolog (Mph) of human herpesvirus entry protein B (HveB) mediates
entry of pseudorabies virus but not herpes simplex virus types 1 and 2.
AB - A mouse member of the immunoglobulin superfamily, originally designated the
murine poliovirus receptor homolog (Mph), was found to be a receptor for the
porcine alphaherpesvirus pseudorabies virus (PRV). This mouse protein, designated
here murine herpesvirus entry protein B (mHveB), is most similar to one of three
related human alphaherpesvirus receptors, the one designated HveB and also known
as poliovirus receptor-related protein 2. Hamster cells resistant to PRV entry
became susceptible upon expression of a cDNA encoding mHveB. Anti-mHveB antibody
and a soluble protein composed of the mHveB ectodomain inhibited mHveB-dependent
PRV entry. Expression of mHveB mRNA was detected in a variety of mouse cell
lines, but anti-mHveB antibody inhibited PRV infection in only a subset of these
cell lines, indicating that mHveB is the principal mediator of PRV entry into
some mouse cell types but not others. Coexpression of mHveB with PRV gD, but not
herpes simplex virus type 1 (HSV-1) gD, inhibited entry activity, suggesting that
PRV gD may interact directly with mHveB as a ligand that can cause interference.
By analogy with HSV-1, envelope-associated PRV gD probably also interacts
directly with mHveB during viral entry.
PMID- 10196355
TI - Packaging cell lines for simian foamy virus type 1 vectors.
AB - Foamy viruses are nonpathogenic retroviruses that offer several unique
opportunities for gene transfer in various cell types from different species. We
have previously demonstrated the utility of simian foamy virus type 1 (SFV-1) as
a vector system by transient expression assay (M. Wu et al., J. Virol. 72:3451
3454, 1998). In this report, we describe the first stable packaging cell lines
for foamy virus vectors based on SFV-1. We developed two packaging cell lines in
which the helper DNA is placed under the control of either a constitutive
cytomegalovirus (CMV) immediate-early gene or inducible tetracycline promoter for
expression. Although the constitutive packaging expressing cell line had a higher
copy number of packaging DNA, the inducible packaging cell line produced four
times more vector particles. This result suggested that the structural gene
products in the constitutively expressing packaging cell line were expressed at a
level that is not toxic to the cells, and thus vector production was reduced. The
SFV-1 vector in the presence of vesicular stomatitis virus envelope protein G
(VSV-G) produced an insignificant level of transduction, indicating that foamy
viruses could not be pseudotyped with VSV-G to generate high-titer vectors. The
availability of stable packaging cell lines represents a step toward the use of
an SFV-1 vector delivery system that will allow scaled-up production of vector
stocks for gene therapy.
PMID- 10196356
TI - Incomplete regulation of NF-kappaB by IkappaBalpha during respiratory syncytial
virus infection in A549 cells.
AB - Respiratory syncytial virus (RSV) infection of airway epithelial cells results in
persistent NF-kappaB activation and NF-kappaB-mediated interleukin-8 production.
Previous studies in airway epithelial cells demonstrated that tumor necrosis
factor alpha (TNF-alpha)-induced NF-kappaB activation is transient due to
regulation by IkappaBalpha. However, during RSV infection, IkappaBalpha has only
a partial inhibitory effect on NF-kappaB activation. Studies presented here
demonstrate that neither increased IkappaBalpha production which occurs as a
result of RSV-induced NF-kappaB activation nor inhibition of proteasome-mediated
IkappaBalpha degradation results in a reversal of RSV-induced NF-kappaB
activation. Thus, while manipulation of IkappaBalpha results in reversal of TNF
alpha-induced NF-kappaB activation, manipulation of IkappaBalpha does not result
in a reversal of RSV-induced NF-kappaB activation.
PMID- 10196357
TI - Detection of simian immunodeficiency virus Gag-specific CD8(+) T lymphocytes in
semen of chronically infected rhesus monkeys by cell staining with a tetrameric
major histocompatibility complex class I-peptide complex.
AB - Evaluation of human immunodeficiency virus type 1-specific mucosal cytotoxic T
lymphocytes can be hampered by limited cell yields from mucosal sites. We sought
to characterize virus-specific CD8(+) T lymphocytes with cytotoxic activity in
the male genital tracts of SIVmac-infected rhesus monkeys by using a peptide
epitope-specific functional T-cell assay and a tetrameric major
histocompatibility complex class I-peptide complex. This tetrameric complex was
constructed with the rhesus monkey HLA-A homolog molecule Mamu-A*01 and a
dominant-epitope 9-amino-acid fragment of SIVmac Gag (p11C, C-M). The proportion
of tetramer-positive CD8(+) T cells in semen of SIVmac-infected monkeys ranged
from 5.9 to 22.0%. By the use of a standard 51Cr release assay, these cells were
found to have peptide epitope-specific cytolytic activity after in vitro
expansion. Four-color flow-cytometric analysis of these seminal tetramer-positive
CD8(+) T cells demonstrated that they express memory-associated (CD62L- CD45RA-)
and activation-associated (CD11a+ Fas+ HLA-DR+) molecules. The present
experiments illustrate the power of tetramer technology for evaluating antigen
specific CD8(+) T lymphocytes in a mucosal tissue compartment.
PMID- 10196358
TI - The human HLA-A*0201 allele, expressed in hamster cells, is not a high-affinity
receptor for adenovirus type 5 fiber.
AB - The coxsackie B virus and adenovirus receptor (CAR) and the major
histocompatibility complex (MHC) class I alpha2 domain have been identified as
high-affinity cell receptors for adenovirus type 5 (Ad5) fiber. In this study we
show that CAR but not MHC class I allele HLA-A*0201 binds to Ad5 with high
affinity when expressed on hamster cells. When both receptors are coexpressed on
the cell surface of hamster cells, Ad5 fiber bind to a single high-affinity
receptor, which is CAR.
PMID- 10196359
TI - Gastrointestinal epithelium is an early extrathymic site for increased prevalence
of CD34(+) progenitor cells in contrast to the thymus during primary simian
immunodeficiency virus infection.
AB - The objective of this study was to determine the effects of primary simian
immunodeficiency virus (SIV) infection on the prevalence and phenotype of
progenitor cells present in the gastrointestinal epithelia of SIV-infected rhesus
macaques, a primate model for human immunodeficiency virus pathogenesis. The
gastrointestinal epithelium was residence to progenitor cells expressing CD34
antigen, a subset of which also coexpressed Thy-1 and c-kit receptors, suggesting
that the CD34(+) population in the intestine comprised a subpopulation of
primitive precursors. Following experimental SIVmac251 infection, an early
increase in the proportions of CD34(+) Thy-1(+) and CD34(+) c-kit+ progenitor
cells was observed in the gastrointestinal epithelium. In contrast, the
proportion of CD34(+) cells in the thymus declined during primary SIV infection,
which was characterized by a decrease in the frequency of CD34(+) Thy-1(+)
progenitor cells. A severe depletion in the frequency of CD4-committed CD34(+)
progenitors was observed in the gastrointestinal epithelium 2 weeks after SIV
infection which persisted even 4 weeks after infection. A coincident increase in
the frequency of CD8- committed CD34(+) progenitor cells was observed during
primary SIV infection. These results indicate that in contrast to the primary
lymphoid organs such as the thymus, the gastrointestinal epithelium may be an
early extrathymic site for the increased prevalence of both primitive and
committed CD34(+) progenitor cells. The gastrointestinal epithelium may
potentially play an important role in maintaining T-cell homeostasis in the
intestinal mucosa during primary SIV infection.
PMID- 10196360
TI - Identification and initial characterization of the murine gammaherpesvirus 68
gene M3, encoding an abundantly secreted protein.
AB - Several viruses, including members of the gammaherpesvirus family, encode
proteins that are secreted into the extracellular environment. We have identified
an abundant 44-kDa secreted protein that is present in the supernatant of
fibroblasts infected with murine gammaherpesvirus 68 (gammaHV68; also referred to
as MHV-68) but not in that of uninfected fibroblasts. Sequence analysis of the
amino terminus and of internal peptides revealed that this protein is encoded by
the gammaHV68 M3 open reading frame (ORF). The amino-terminal sequence of the
secreted protein starts at residue 25 of the M3 ORF, consistent with the first 24
residues functioning as a signal peptide. Northern blot analysis revealed a
single abundant approximately 1.4-kb early-late lytic transcript encoded by the
M3 ORF. Analysis of a partial cDNA clone and subsequent analyses of products of
rapid amplification of cDNA ends coupled with S1 nuclease protection assays
demonstrate that the M3 protein is encoded by an unspliced, polyadenylated mRNA
initiating at bp 7294 and terminating at bp 6007 of the gammaHV68 genome. The 3'
end of the M3 transcript maps 9 bp downstream of a consensus polyadenylation
signal. Thus, the predicted M3 ORF is a functional gene that encodes an abundant
secreted protein which is a candidate for interacting with host cellular
receptors or cytokines.
PMID- 10196361
TI - Embryonic lethality and vascular defects in mice lacking the Notch ligand
Jagged1.
AB - The Notch signaling pathway is an evolutionarily conserved intercellular
signaling mechanism essential for embryonic development in mammals. Mutations in
the human JAGGED1 ( JAG1 ) gene, which encodes a ligand for the Notch family of
transmembrane receptors, cause the autosomal dominant disorder Alagille syndrome.
We have examined the in vivo role of the mouse Jag1 gene by creating a null
allele through gene targeting. Mice homozygous for the Jag1 mutation die from
hemorrhage early during embryogenesis, exhibiting defects in remodeling of the
embryonic and yolk sac vasculature. We mapped the Jag1 gene to mouse chromosome
2, in the vicinity of the Coloboma ( Cm ) deletion. Molecular and complementation
analyses revealed that the Jag1 gene is functionally deleted in the Cm mutant
allele. Mice heterozygous for the Jag1 null allele exhibit an eye dysmorphology
similar to that of Cm /+ heterozygotes, but do not exhibit other phenotypes
characteristic of Cm /+ mice or of humans with Alagille syndrome. These results
establish the phenotype of Cm /+ mice as a contiguous gene deletion syndrome and
demonstrate that Jag1 is essential for remodeling of the embryonic vasculature.
PMID- 10196362
TI - Polyglutamine-expanded androgen receptors form aggregates that sequester heat
shock proteins, proteasome components and SRC-1, and are suppressed by the HDJ-2
chaperone.
AB - Spinal bulbar muscular atrophy is a neurodegenerative disorder caused by a
polyglutamine expansion in the androgen receptor (AR). We show in transiently
transfected HeLa cells that an AR containing 48 glutamines (ARQ48) accumulates in
a hormone-dependent manner in both cytoplasmic and nuclear aggregates. Electron
microscopy reveals both types of aggregates to have a similar ultrastructure.
ARQ48 aggregates sequester mitochondria and steroid receptor coactivator 1 and
stain positively for NEDD8, Hsp70, Hsp90 and HDJ-2/HSDJ. Co-expression of HDJ
2/HSDJ significantly represses aggregate formation. ARQ48 aggregates also label
with antibodies recognizing the PA700 proteasome caps but not 20S core particles.
These results suggest that ARQ48 accumulates due to protein misfolding and a
breakdown in proteolytic processing. Furthermore, the homeostatic disturbances
associated with aggregate formation may affect normal cell function.
PMID- 10196363
TI - Mutation of a putative mitochondrial iron transporter gene (ABC7) in X-linked
sideroblastic anemia and ataxia (XLSA/A).
AB - X-linked sideroblastic anemia and ataxia (XLSA/A) is a recessive disorder
characterized by an infantile to early childhood onset of non-progressive
cerebellar ataxia and mild anemia with hypochromia and microcytosis. A gene
encoding an ATP-binding cassette (ABC) transporter was mapped to Xq13, a region
previously shown by linkage analysis to harbor the XLSA/A gene. This gene, ABC7,
is an ortholog of the yeast ATM1 gene whose product localizes to the
mitochondrial inner membrane and is involved in iron homeostasis. The full-length
ABC7 cDNA was cloned and the entire coding region screened for mutations in a
kindred in which five male members manifested XLSA/A. An I400M variant was
identified in a predicted transmembrane segment of the ABC7 gene in patients with
XLSA/A. The mutation was shown to segregate with the disease in the family and
was not detected in at least 600 chromosomes of general population controls.
Introduction of the corresponding mutation into the Saccharomyces cerevisiae ATM1
gene resulted in a partial loss of function of the yeast Atm1 protein. In
addition, the human wild-type ABC7 protein was able to complement ATM1 deletion
in yeast. These data indicate that ABC7 is the causal gene of XLSA/A and that
XLSA/A is a mitochondrial disease caused by a mutation in the nuclear genome.
PMID- 10196364
TI - Generation of an approximately 2.4 Mb human X centromere-based minichromosome by
targeted telomere-associated chromosome fragmentation in DT40.
AB - A linear mammalian artificial chromosome (MAC) will require at least three types
of functional element: a centromere, two telomeres and origins of replication. As
yet, our understanding of these elements, as well as many other aspects of
structure and organization which may be critical for a fully functional mammalian
chromosome, remains poor. As a way of defining these various requirements,
minichromosome reagents are being developed and analysed. Approaches for
minichromosome generation fall into two broad categories: de novo assembly from
candidate DNA sequences, or the fragmentation of an existing chromosome to reduce
it to a minimal size. Here we describe the generation of a human minichromosome
using the latter, top-down, approach. A human X chromosome, present in a DT40
human microcell hybrid, has been manipulated using homologous recombination and
the targeted seeding of a de novo telomere. This strategy has generated a linear
approximately 2.4 Mb human X centromere-based minichromosome capped by two
artificially seeded telomeres: one immediately flanking the centromeric alpha
satellite DNA and the other targeted to the zinc finger gene ZXDA in Xp11.21. The
chromosome retains an alpha-satellite domain of approximately 1. 8 Mb, a small
array of gamma-satellite repeat ( approximately 40 kb) and approximately 400 kb
of Xp proximal DNA sequence. The mitotic stability of this minichromosome has
been examined, both in DT40 and following transfer into hamster and human cell
lines. In all three backgrounds, the minichromosome is retained efficiently, but
in the human and hamster microcell hybrids its copy number is poorly regulated.
This approach of engineering well-defined chromosome reagents will allow key
questions in MAC development (such as whether a lower size limit exists) to be
addressed. In addition, the 2.4 Mb minichromosome described here has potential to
be developed as a vector for gene delivery.
PMID- 10196365
TI - A Huntington's disease CAG expansion at the murine Hdh locus is unstable and
associated with behavioural abnormalities in mice.
AB - Huntington's disease (HD) is a dominant disorder characterized by premature and
progressive neurodegeneration. In order to generate an accurate model of the
disease, we introduced an HD-like mutation (an extended stretch of 72-80 CAG
repeats) into the endogenous mouse Hdh gene. Analysis of the mutation in vivo
reveals significant levels of germline instability, with expansions, contractions
and sex-of-origin effects in evidence. Mice expressing full-length mutant protein
display abnormal social behaviour in the absence of acute neurodegeneration.
Given that psychiatric changes, including irritability and aggression, are common
findings in HD patients, our data are consistent with the hypothesis that some
clinical features of HD may be caused by pathological processes that precede
gross neuronal cell death. This implies that effective treatment of HD may
require an understanding and amelioration of these dysfunctional processes,
rather than simply preventing the premature death of neurons in the brain. These
mice should facilitate the investigation of the molecular mechanisms that
underpin the pathway from genotype to phenotype in HD.
PMID- 10196366
TI - The RNA-binding properties of SMN: deletion analysis of the zebrafish orthologue
defines domains conserved in evolution.
AB - Spinal muscular atrophy (SMA) is a common autosomal recessive disorder that
results in the degeneration of spinal motor neurons. SMA is caused by alterations
of the survival motor neuron ( SMN ) gene which encodes a novel protein of
hitherto unclear function. The SMN protein associates with ribonucleoprotein
particles involved in RNA processing and exhibits an RNA-binding capacity. We
have isolated the zebrafish Danio rerio and nematode Caenorhabditis elegans
orthologues and have found that the RNA-binding capacity is conserved across
species. Purified recombinant SMN proteins from both species showed selectivity
to poly(G) homopolymer RNA in vitro, similar to that of the human protein.
Studying deletions of the zebrafish SMN protein, we defined an RNA-binding
element in exon 2a, which is highly conserved across species, and revealed that
its binding activity is modulated by protein domains encoded by exon 2b and exon
3. Finally, the deleted recombinant zebrafish protein mimicking an SMA frameshift
mutation showed a dramatic change in vitro in the formation of the RNA-protein
complexes. These observations indicate that the RNA-binding capacity of SMN is an
evolutionarily conserved function and further support the view that defects in
RNA metabolism most likely account for the pathogenesis of SMA.
PMID- 10196367
TI - A novel imprinted gene, encoding a RING zinc-finger protein, and overlapping
antisense transcript in the Prader-Willi syndrome critical region.
AB - We describe a complex imprinted locus in chromosome 15q11-q13 that encodes two
genes, ZNF127 and ZNF127AS. The ZNF127 gene encodes a protein with a RING (C3HC4)
zinc-finger and multiple C3H zinc-finger motifs, the former being closely related
to a protein from variola major virus, the smallpox etiological agent. These
motifs allow prediction of ZNF127 function as a ribonucleoprotein. The intronless
ZNF127 gene is expressed ubiquitously, but the entire coding sequence and 5' CpG
island overlaps a second gene, ZNF127AS, that is transcribed from the antisense
strand with a different transcript size and pattern of expression. Allele
specific analysis shows that ZNF127 is expressed only from the paternal allele.
Consistent with this expression pattern, in the brain the ZNF127 5' CpG island is
completely unmethylated on the paternal allele but methylated on the maternal
allele. Analyses of adult testis, sperm and fetal oocytes demonstrates a gametic
methylation imprint with unmethylated paternal germ cells. Recent findings
indicate that ZNF127 is part of the coordinately regulated imprinted domain
affected in Prader-Willi syndrome patients with imprinting mutations. Therefore,
ZNF127 and ZNF127AS are novel imprinted genes that may be associated with some of
the clinical features of the polygenic Prader-Willi syndrome.
PMID- 10196368
TI - Imprinting of a RING zinc-finger encoding gene in the mouse chromosome region
homologous to the Prader-Willi syndrome genetic region.
AB - A novel locus in the human Prader-Willi syndrome (PWS) region encodes the
imprinted ZNF127 and antisense ZNF127AS genes. Here, we show that the mouse
ZNF127 ortholog, Zfp127, encodes a homologous putative zinc-finger polypeptide,
with a RING (C3HC4) and three C3H zinc-finger domains that suggest function as a
ribonucleoprotein. By the use of RT-PCR across an in-frame hexamer tandem repeat
and RNA from a Mus musculus x M.spretus F1interspecific cross, we show that
Zfp127 is expressed only from the paternal allele in brain, heart and kidney.
Similarly, Zfp127 is expressed in differentiated cells derived from androgenetic
embryonic stem cells and normal embryos but not those from parthogenetic
embryonic stem cells. We hypothesize that the gametic imprint may be set, at
least in part, by the transcriptional activity of Zfp127 in pre- and post-meiotic
male germ cells. Therefore, Zfp127 is a novel imprinted gene that may play a role
in the imprinted phenotype of mouse models of PWS.
PMID- 10196369
TI - Genome-wide scan for autism susceptibility genes. Paris Autism Research
International Sibpair Study.
AB - Family and twin studies have suggested a genetic component in autism. We
performed a genome-wide screen with 264 microsatellites markers in 51 multiplex
families, using non-parametric linkage methods. Families were recruited by a
collaborative group including clinicians from Sweden, France, Norway, the USA,
Italy, Austria and Belgium. Using two-point and multipoint affected sib-pair
analyses, 11 regions gave nominal P -values of 0.05 or lower. Four of these
regions overlapped with regions on chromosomes 2q, 7q, 16p and 19p identified by
the first genome-wide scan of autism performed by the International Molecular
Genetic Study of Autism Consortium. Another of our potential susceptibility
regions overlapped with the 15q11-q13 region identified in previous candidate
gene studies. Our study revealed six additional regions on chromosomes 4q, 5p,
6q, 10q, 18q and Xp. We found that the most significant multipoint linkage was
close to marker D6S283 (maximum lod score = 2.23, P = 0.0013).
PMID- 10196370
TI - Formation of polyglutamine inclusions in non-CNS tissue.
AB - Huntington's disease (HD) is one of a class of inherited progressive
neurodegenerative disorders that are caused by a CAG/polyglutamine repeat
expansion. We have previously generated mice that are transgenic for exon 1 of
the HD gene carrying highly expanded CAG repeats which develop a progressive
movement disorder and weight loss with similarities to HD. Neuronal inclusions
composed of the exon 1 protein and ubiquitin are present in specific brain
regions prior to onset of the phenotype, which in turn occurs long before
specific neurodegeneration can be detected. In this report we have extended the
search for polyglutamine inclusions to non-neuronal tissues. Outside the central
nervous system (CNS), inclusions were identified in a variety of post-mitotic
cells. This is consistent with a concentration-dependent nucleation and
aggregation model of inclusion formation and indicates that brain-specific
factors are not necessary for this process. To possibly gain insights into the
wasting that is observed in the human disease, we have conducted a detailed
analysis of the timing and progression of inclusion formation in skeletal muscle
and an investigation into the cause of the severe muscle atrophy that occurs in
the mouse model. The formation of inclusions in non-CNS tissues will be
particularly useful with respect to in vivo monitoring of pharmaceutical agents
selected for their ability to prevent polyglutamine aggregation in vitro, without
the requirement that the agent can cross the blood-brain barrier in the first
instance.
PMID- 10196372
TI - Adenoviral gene therapy of the Tay-Sachs disease in hexosaminidase A-deficient
knock-out mice.
AB - The severe neurodegenerative disorder, Tays-Sachs disease, is caused by a beta
hexosaminidase alpha-subunit deficiency which prevents the formation of lysosomal
heterodimeric alpha-beta enzyme, hexosaminidase A (HexA). No treatment is
available for this fatal disease; however, gene therapy could represent a
therapeutic approach. We previously have constructed and characterized, in vitro,
adenoviral and retroviral vectors coding for alpha- and beta-subunits of the
human beta-hexosaminidases. Here, we have determined the in vivo strategy which
leads to the highest HexA activity in the maximum number of tissues in hexA
deficient knock-out mice. We demonstrated that intravenous co-administration of
adenoviral vectors coding for both alpha- and beta-subunits, resulting in
preferential liver transduction, was essential to obtain the most successful
results. Only the supply of both subunits allowed for HexA overexpression leading
to massive secretion of the enzyme in serum, and full or partial enzymatic
activity restoration in all peripheral tissues tested. The enzymatic correction
was likely to be due to direct cellular transduction by adenoviral vectors and/or
uptake of secreted HexA by different organs. These results confirmed that the
liver was the preferential target organ to deliver a large amount of secreted
proteins. In addition, the need to overexpress both subunits of heterodimeric
proteins in order to obtain a high level of secretion in animals defective in
only one subunit is emphasized. The endogenous non-defective subunit is otherwise
limiting.
PMID- 10196371
TI - Mismatch repair gene defects contribute to the genetic basis of double primary
cancers of the colorectum and endometrium.
AB - Hereditary non-polyposis colorectal cancer (HNPCC) is a dominantly inherited
cancer syndrome caused by germline defects of mismatch repair (MMR) genes.
Endometrial cancer is the most common extracolonic neoplasm in HNPCC and is the
primary clinical manifestation of the syndrome in some families. The cumulative
incidence of endometrial cancer among HNPCC mutation carriers is high, estimated
to be from 22 to 43%. We hypothesized that women with double primary cancers of
the colorectum and endometrium are likely to be members of HNPCC families. In
order to determine how frequently HNPCC manifests in the context of double
primary cancers, we examined alterations of two MMR genes, hMSH2 and hMLH1, in 40
unrelated women affected with double primary cancers. These cases were identified
using hospital-based and population-based cancer registries in Ontario, Canada.
MMR gene mutations were screened by single-strand conformation polymorphism
analysis and confirmed by direct sequencing. Eighteen percent (seven of 40) were
found to harbor mutations of one of the two MMR genes. Analysis of colorectal
and/or endometrial tumors of mutation-negative probands found microsatellite
instability in seven of 20 cases. Six of seven mutation-positive probands had
strong family histories suggestive of HNPCC. First degree relatives of mutation
positive probands had a very high relative risk (RR) of colorectal cancer (RR =
8.1, CI 3. 5-15.9) and endometrial cancer (RR = 23.8, CI 6.4-61.0). The relative
risk of mutation-negative cases was 2.8 (CI 1.7-4.5) for colorectal cancer and
5.4 (CI 2.0-11.7) for endometrial cancer. We recommend that all double primary
patients with cancers at these sites should have a genetic evaluation, including
molecular analysis for HNPCC where appropriate.
PMID- 10196373
TI - Impaired synaptic plasticity in mice carrying the Huntington's disease mutation.
AB - Cognitive impairment is an early symptom of Huntington's disease (HD). Mice
engineered to carry the HD mutation in the endogenous huntingtin gene showed a
significant reduction in long-term potentiation (LTP), a measure of synaptic
plasticity often thought to be involved in memory. However, LTP could be induced
in mutant slices by an 'enhanced' tetanic stimulus, implying that the LTP
producing mechanism is intact in mutant mice, but that their synapses are less
able to reach the threshold for LTP induction. Mutant mice showed less post
tetanic potentiation than wild-type animals, and also showed decreased paired
pulse facilitation, suggesting that excitatory synapses in HD mutant mice are
impaired in their ability to sustain transmission during repetitive stimulation.
We show that mutants, while normal in their ability to transmit at low
frequencies, released significantly less glutamate during higher frequency
synaptic activation. Thus, a reduced ability of Huntington synapses to respond to
repetitive synaptic demand of even moderate frequency could result not only in a
functional impairment of LTP induction, but could also serve as a substrate for
the cognitive symptoms that comprise the early-stage pathology of HD.
PMID- 10196374
TI - Zim1, a maternally expressed mouse Kruppel-type zinc-finger gene located in
proximal chromosome 7.
AB - In analysis of a conserved region of proximal mouse chromosome 7 and human
chromosome 19q, we have isolated a novel mouse gene, Zim1 (imprinted zinc-finger
gene 1), encoding a typical Kruppel-type (C2H2) zinc-finger protein, located
within 30 kb of a known imprinted gene, Peg3 (paternally expressed gene 3). Our
studies demonstrate that Zim1 is also imprinted; the gene is expressed mainly
from the maternal allele and at high levels only during embryonic and neonatal
stages. In contrast to most tissues, Zim1 is expressed biallelically in neonatal
and adult brain with slightly more input from the maternal allele. Zim1 produces
multiple transcripts that range in size from 7.5 to 15 kb. The 7.5 kb transcript
is expressed at highest levels and appears to be embryo specific. Whole mount in
situ hybridization analysis indicates that Zim1 is expressed at significant
levels in the apical ectodermal ridge of the limb buds during embryogenesis,
suggesting a potential role of Zim1 in limb formation. We have identified the
potential human ortholog of Zim1 near PEG3 in a conserved, gene-rich region of
human chromosome 19q13.4. The close juxtaposition of reciprocally imprinted genes
has also been seen in other imprinted regions, such as human 11p15.5/Mmu7 ( H19 /
Igf2 ) and suggests that the two genes may be co-regulated. These and other data
suggest the presence of an unexplored, conserved imprinted domain in human
chromosome 19q13.4 and proximal Mmu7.
PMID- 10196375
TI - Dysferlin is a plasma membrane protein and is expressed early in human
development.
AB - Recently, a single gene, DYSF, has been identified which is mutated in patients
with limb-girdle muscular dystrophy type 2B (LGMD2B) and with Miyoshi myopathy
(MM). This is of interest because these diseases have been considered as two
distinct clinical conditions since different muscle groups are the initial
targets. Dysferlin, the protein product of the gene, is a novel molecule without
homology to any known mammalian protein. We have now raised a monoclonal antibody
to dysferlin and report on the expression of this new protein: immunolabelling
with the antibody (designated NCL-hamlet) demonstrated a polypeptide of
approximately 230 kDa on western blots of skeletal muscle, with localization to
the muscle fibre membrane by microscopy at both the light and electron
microscopic level. A specific loss of dysferlin labelling was observed in
patients with mutations in the LGMD2B/MM gene. Furthermore, patients with two
different frameshifting mutations demonstrated very low levels of immunoreactive
protein in a manner reminiscent of the dystrophin expressed in many Duchenne
patients. Analysis of human fetal tissue showed that dysferlin was expressed at
the earliest stages of development examined, at Carnegie stage 15 or 16
(embryonic age 5-6 weeks). Dysferlin is present, therefore, at a time when the
limbs start to show regional differentiation. Lack of dysferlin at this critical
time may contribute to the pattern of muscle involvement that develops later,
with the onset of a muscular dystrophy primarily affecting proximal or distal
muscles.
PMID- 10196376
TI - Different targets for the fragile X-related proteins revealed by their distinct
nuclear localizations.
AB - Fragile X syndrome is caused by the absence of the fragile X mental retardation
protein (FMRP). FMRP and its structural homologues FXR1P and FXR2P form a family
of RNA-binding proteins (FXR proteins). The three proteins associate with
polyribosomes as cytoplasmic mRNP particles. Here we show that small amounts of
FMRP, FXR1P and FXR2P shuttle between cytoplasm and nucleus. Mutant FMRP of a
severely affected fragile X patient (FMRPI304N) does not associate with
polyribosomes and shuttles more frequently than normal FMRP, indicating that the
association with polyribosomes regulates the shuttling process. Using leptomycin
B we demonstrate that transport of the FXR proteins out of the nucleus is
mediated by the export receptor exportin1. Finally, inactivation of the nuclear
export signal in two FXR proteins shows that FMRP shuttles between cytoplasm and
nucleoplasm, while FXR2P shuttles between cytoplasm and nucleolus. Therefore,
molecular dissection of the shuttling routes used by the FXR proteins suggests
that they transport different RNAs.
PMID- 10196377
TI - Identical mutation in patients with limb girdle muscular dystrophy type 2B or
Miyoshi myopathy suggests a role for modifier gene(s).
AB - Limb girdle muscular dystrophy type 2B (LGMD2B) and Miyoshi myopathy (MM), a
distal muscular dystrophy, are both caused by mutations in the recently cloned
gene dysferlin, gene symbol DYSF. Two large pedigrees have been described which
have both types of patient in the same families. Moreover, in both pedigrees
LGMD2B and MM patients are homozygous for haplotypes of the critical region. This
suggested that the same mutation in the same gene would lead to both LGMD2B or MM
in these families and that additional factors were needed to explain the
development of the different clinical phenotypes. In the present paper we show
that in one of these families Pro791 of dysferlin is changed to an Arg residue.
Both the LGMD2B and MM patients in this kindred are homozygous for this mutation,
as are four additional patients from two previously unpublished families.
Haplotype analyses suggest a common origin of the mutation in all the patients.
On western blots of muscle, LGMD2B and MM patients show a similar abundance in
dysferlin staining of 15 and 11%, respectively. Normal tissue sections show that
dysferlin localizes to the sarcolemma while tissue sections from MM and LGMD
patients show minimal staining which is indistinguishable between the two types.
These findings emphasize the role for the dysferlin gene as being responsible for
both LGMD2B and MM, but that the distinction between these two clinical
phenotypes requires the identification of additional factor(s), such as modifier
gene(s).
PMID- 10196378
TI - Extremely complex repeat shuffling during germline mutation at human
minisatellite B6.7.
AB - Human minisatellite B6.7 is a highly variable locus showing extensive
heterozygosity with alleles ranging from six to >500 repeat units. Paternal and
maternal mutation rates to new length alleles were estimated from pedigrees at
7.0 and 3.9% per gamete, respectively, indicating that B6.7 is one of the most
unstable minisatellites isolated to date. Mutation at this locus was also
analysed by small pool PCR of sperm and blood DNA. Male germline instability
varied from <0.8 to 14% per allele and increased with tandem array size. In
contrast, the frequency of mutants in somatic (blood) DNA was far lower (<0.5%),
consistent with a meiotic origin of germline mutants. Sperm mutants were further
characterized by minisatellite variant repeat mapping using four major
polymorphic sites within the B6.7 repeats. This highly informative system
revealed a wide variety of changes in allele structure, including simple intra
allelic duplications and deletions and more complicated inter- and intra-allelic
transfers of repeat blocks, as seen at other human minisatellites. The main mode
of sperm mutation, however, resulted in extremely complex allele reorganization
with evidence of inter-allelic transfer plus the generation of novel repeats by
rearrangement at the sub-repeat level, suggesting that recombinational
instability at B6.7 is a complex multistep process.
PMID- 10196379
TI - Germline BRCA1 alterations in a population-based series of ovarian cancer cases.
AB - The objective of this study was to provide more accurate frequency estimates of
breast cancer susceptibility gene 1 ( BRCA1 ) germline alterations in the ovarian
cancer population. To achieve this, we determined the prevalence of BRCA1
alterations in a population-based series of consecutive ovarian cancer cases.
This is the first population-based ovarian cancer study reporting BRCA1
alterations derived from a comprehensive screen of the entire coding region. One
hundred and seven ovarian cancer cases were analyzed for BRCA1 alterations using
the RNase mismatch cleavage assay followed by direct sequencing. Two truncating
mutations, 962del4 and 3600del11, were identified. Both patients had a family
history of breast or ovarian cancer. Several novel as well as previously reported
uncharacterized variants were also identified, some of which were associated with
a family history of cancer. The frequency distribution of common polymorphisms
was determined in the 91 Caucasian cancer cases in this series and 24 sister
controls using allele-specific amplification. The rare form of the Q356R
polymorphism was significantly ( P = 0.03) associated with a family history of
ovarian cancer, suggesting that this polymorphism may influence ovarian cancer
risk. In summary, our data suggest a role for some uncharacterized variants and
rare forms of polymorphisms in determining ovarian cancer risk, and highlight the
necessity to screen for missense alterations as well as truncating mutations in
this population.
PMID- 10196380
TI - Analysis of myocilin mutations in 1703 glaucoma patients from five different
populations.
AB - A glaucoma locus, GLC1A, was identified previously on chromosome 1q. A gene
within this locus (encoding the protein myocilin) subsequently was shown to
harbor mutations in 2-4% of primary open angle glaucoma patients. A total of 1703
patients was screened from five different populations representing three racial
groups. There were 1284 patients from primarily Caucasian populations in Iowa
(727), Australia (390) and Canada (167). A group of 312 African American patients
was from New York City and 107 Asian patients from Japan. Overall, 61 different
myocilin sequence variations were identified. Of the 61 variations, 21 were
judged to be probable disease-causing mutations. The number of probands found to
harbor such mutations in each population was: Iowa 31/727 (4.3%), African
Americans from New York City 8/312 (2.6%), Japan 3/107 (2.8%), Canada 5/167
(3.0%), Australia 11/390 (2.8%) and overall 58/1703 (3. 4%). Overall, 16 (76%) of
21 mutations were found in only one population. The most common mutation
observed, Gln368Stop, was found in 27/1703 (1.6%) glaucoma probands and was found
at least once in all groups except the Japanese. Studies of genetic markers
flanking the myocilin gene suggest that most cases of the Gln368Stop mutations
are descended from a common founder. Although the specific mutations found in
each of the five populations were different, the overall frequency of myocilin
mutations was similar ( approximately 2-4%) in all populations, suggesting that
the increased rate of glaucoma in African Americans is not due to a higher
prevalence of myocilin mutations.
PMID- 10196381
TI - Adrenoleukodystrophy-related protein can compensate functionally for
adrenoleukodystrophy protein deficiency (X-ALD): implications for therapy.
AB - Inherited defects in the peroxisomal ATP-binding cassette (ABC) transporter
adrenoleukodystrophy protein (ALDP) lead to the lethal peroxisomal disorder X
linked adrenoleukodystrophy (X-ALD), for which no efficient treatment has been
established so far. Three other peroxisomal ABC transporters currently are known:
adrenoleukodystrophy-related protein (ALDRP), 70 kDa peroxisomal membrane protein
(PMP70) and PMP70- related protein. By using transient and stable overexpression
of human cDNAs encoding ALDP and its closest relative ALDRP, we could restore the
impaired peroxisomal beta-oxidation in fibroblasts of X-ALD patients. The
pathognomonic accumulation of very long chain fatty acids could also be prevented
by overexpression of ALDRP in immortalized X-ALD cells. Immunofluorescence
analysis demonstrated that the functional replacement of ALDP by ALDRP was not
due to stabilization of the mutated ALDP itself. Moreover, we were able to
restore the peroxisomal beta-oxidation defect in the liver of ALDP-deficient mice
by stimulation of ALDRP and PMP70 gene expression through a dietary treatment
with the peroxisome proliferator fenofibrate. These results suggest that a
correction of the biochemical defect in X-ALD could be possible by drug-induced
overexpression or ectopic expression of ALDRP.
PMID- 10196382
TI - DNA pooling identifies QTLs on chromosome 4 for general cognitive ability in
children.
AB - General cognitive ability (g), which is related to many aspects of brain
functioning, is one of the most heritable traits in neuroscience. Similarly to
other heritable quantitatively distributed traits, genetic influence on g is
likely to be due to the combined action of many genes of small effect
[quantitative trait loci (QTLs)], perhaps several on each chromosome. We used DNA
pooling for the first time to search a chromosome systematically with a dense map
of DNA markers for allelic associations with g. We screened 147 markers on
chromosome 4 such that 85% of the chromosome were estimated to be within 1 cM of
a marker. Comparing pooled DNA from 51 children of high g and from 51 controls of
average g, 11 significant QTL associations emerged. The association with three of
these 11 markers ( D4S2943, MSX1 and D4S1607 ) replicated using DNA pooling in
independent samples of 50 children of extremely high g and 50 controls.
Furthermore, all three associations were confirmed when each individual was
genotyped separately ( D4S2943, P = 0. 00045; MSX1, P = 0.011; D4S1607, P =
0.019). Identifying specific genes responsible for such QTL associations will
open new windows in cognitive neuroscience through which to observe pathways
between genes and learning and memory.
PMID- 10196383
TI - Transchromosomal mouse embryonic stem cell lines and chimeric mice that contain
freely segregating segments of human chromosome 21.
AB - At least 8% of all human conceptions have major chromosome abnormalities and the
frequency of chromosomal syndromes in newborns is >0.5%. Despite these disorders
making a large contribution to human morbidity and mortality, we have little
understanding of their aetiology and little molecular data on the importance of
gene dosage to mammalian cells. Trisomy 21, which results in Down syndrome (DS),
is the most frequent aneuploidy in humans (1 in 600 live births, up to 1 in 150
pregnancies world-wide) and is the most common known genetic cause of mental
retardation. To investigate the molecular genetics of DS, we report here the
creation of mice that carry different human chromosome 21 (Hsa21) fragments as a
freely segregating extra chromosome. To produce these 'transchromosomal' animals,
we placed a selectable marker into Hsa21 and transferred the chromosome from a
human somatic cell line into mouse embryonic stem (ES) cells using irradiation
microcell-mediated chromosome transfer (XMMCT). 'Transchromosomal' ES cells
containing different Hsa21 regions ranging in size from approximately 50 to
approximately 0.2 Mb have been used to create chimeric mice. These mice maintain
Hsa21 sequences and express Hsa21 genes in multiple tissues. This novel use of
the XMMCT protocol is applicable to investigations requiring the transfer of
large chromosomal regions into ES or other cells and, in particular, the
modelling of DS and other human aneuploidy syndromes.
PMID- 10196384
TI - Alterations in the CSB gene in three Italian patients with the severe form of
Cockayne syndrome (CS) but without clinical photosensitivity.
AB - Cockayne syndrome (CS) is a rare autosomal recessive disorder characterized by
postnatal growth failure, mental retardation and otherwise clinically
heterogeneous features which commonly include cutaneous photosensitivity.
Cultured cells from sun-sensitive CS patients are hypersensitive to ultraviolet
(UV) light and, following UV irradiation, are unable to restore RNA synthesis
rates to normal levels. This has been attributed to a specific deficiency in CS
cells in the ability to carry out preferential repair of damage in actively
transcribed regions of DNA. We report here a cellular and molecular analysis of
three Italian CS patients who were of particular interest because none of them
was sun-sensitive, despite showing most of the features of the severe form of CS,
including the characteristic cellular sensitivity to UV irradiation. They all
were altered in the CSB gene. The genetically related patients CS1PV and CS3PV
were homozygous for the C1436T transition resulting in the change Arg453opal.
Patient CS2PV was a compound heterozygote for two new causative mutations,
insertions of an A at position 1051 and of TGTC at 2053, leading to truncated
proteins of 367 and 681 amino acids. These mutations result in severely truncated
proteins, as do many of those that we previously identified in several sun
sensitive CS-B patients. These observations confirm that the CSB gene is not
essential for viability and cell proliferation, an important issue to be
considered in any speculation on the recently proposed additional function of the
CSB protein in transcription. Our investigations provide data supporting the
notion that other factors, besides the site of the mutation, influence the type
and severity of the CS clinical features.
PMID- 10196385
TI - Actinomycosis and other bronchopulmonary infections with bacterial granules.
AB - Pulmonary infections with formation of bacterial granules are rare. We reviewed
the clinical and pathologic data from 18 cases diagnosed using surgical specimens
in our department during the last 10 years. Three clinicopathologic forms were
observed: endobronchial infections complicating tuberculous sequelae or
bronchiectases (n = 7), tumor-like lesions (n = 8), and diffuse pneumonia (n =
3). The two latter forms contrasted with the former by a male predominance,
association with general debilitating conditions and inflammatory syndrome, and
pathologically by smaller granules often located in parenchymal abscesses or
excavations. The pathologic examination of the bacteria forming the granules
permitted the diagnoses of actinomycosis (n = 10), botryomycosis (n = 7), or
nocardiosis (n = 1). The latter case corresponded to an endobronchial infection.
Both actinomycosis and botryomycosis were encountered in every clinicopathologic
form. At present, pulmonary actinomycosis and related infections rarely seems to
present with chest wall invasion. On the contrary, purely endobronchial forms
represented a large proportion of our cases. Cultures are often difficult and the
clinical appearance is not specific. However, pathologic examination with special
stains must indicate the type of involved microorganism.
PMID- 10196386
TI - Well-differentiated adenocarcinoma, gastric foveolar type, of the extrahepatic
bile ducts: A previously unrecognized and distinctive morphologic variant of bile
duct carcinoma.
AB - Two examples of a rare but distinctive morphologic variant of extremely well
differentiated adenocarcinoma of the extrahepatic bile ducts are reported. One
tumor arose in the common bile duct of a 51-year-old man; the other arose in the
common hepatic duct of a 27-year-old man. Both tumors were composed predominantly
(>95%) of gastric foveolar-type epithelium. Because of their bland nuclear
features, low mitotic index, and focal polypoid and lobular architecture, they
were initially confused with adenomas. Foci of less-differentiated adenocarcinoma
and perineural invasion present in the deep portions of the tumors facilitated
recognition. The neoplastic cells and extracellular mucin were periodic acid
Schiff- and alcian blue-positive. By immunohistochemistry, the tumor cells
expressed cytokeratins 8 and 20 as well as cathepsin D, as reported in normal
foveolar cells. Likewise, p53 overexpression was documented immunohistochemically
in both adenocarcinomas, which also stained with the Ki-67 antibody. Despite the
well-differentiated nature of the neoplasms and their deceptively benign
microscopic appearance, one patient developed recurrence and liver metastasis 5
years after surgery. The other patient is disease-free 2 years following a
segmental resection of the common hepatic duct, cystic duct, and gallbladder. The
cell phenotype of these tumors can be explained by the ability of the bile duct
epithelium to differentiate along gastric cell lines.
PMID- 10196387
TI - Expression of multidrug resistance-associated protein in endometrial carcinomas:
correlation with clinicopathology and prognosis.
AB - The objective of the study reported here was to investigate the expression of
multidrug resistance-associated protein (MRP) in endometrial carcinomas and to
evaluate the relationship between its expression and clinical data. Using
immunohistochemistry, we examined MRP expression in 15 normal endometria, 10
cases of endometrial hyperplasia, and 64 cases of endometrial carcinoma. The
normal endometrial glands were weakly immunopositive throughout the menstrual
cycle. In addition, we found a progressive increase in the MRP expression of the
endometrial hyperplasias. Of the 64 cases of endometrial carcinoma, 62 (97%)
expressed MRP. Of these 62 cases, 34 (55%) showed strong immunostaining (>/=50%)
and 28 (45%) showed weak immunostaining (<50%). In particular, the intensity of
the immunostaining was very strong in 25 (71%) of the 35 grade 1 carcinomas.
There was a significant difference in MRP expression between the grade 1
carcinomas and the more poorly differentiated carcinomas (grade 2 or grade 3) (P
<.01), especially at stages 1a and 1b (P <.001). However, beyond stage 1c, there
was no significant difference in MRP immunoreactivity between the histologic
differentiations. Furthermore, beyond stage 1c, those patients with strongly MRP
positive carcinomas had a relatively poorer survival rate than those with weakly
MRP-positive carcinomas (P <.05). We concluded that MRP immunoreactivity was
already present in normal endometrium and showed a progressive increase from
endometrial hyperplasia to well-differentiated carcinoma. Beyond stage 1c,
strongly MRP-positive carcinoma indicated a poorer survival rate.
PMID- 10196388
TI - Renal angiomyolipoma resembling gastrointestinal stromal tumor with skenoid
fibers.
AB - We report an unusual case of renal angiomyolipoma occurring in 68-year-old man.
The tumor lacked well-developed vascular and adipose components and was composed
almost exclusively of smooth muscle cells. Numerous skenoid-like periodic acid
Schiff-positive globules were interspersed between the tumor cells; the lesion
therefore closely resembled a low-grade stromal tumor of the gastrointestinal
tract. The HMB45-positive/CD34-negative immunophenotype was essential for the
diagnosis of angiomyolipoma. Neither gastrointestinal tumor nor any signs of
tuberous sclerosis were found. This lesion should be included in the list of
morphologic variations of angiomyolipoma, which may cause diagnostic
difficulties.
PMID- 10196389
TI - Myxoid variant of follicular dendritic cell sarcoma arising in the breast.
AB - Follicular dendritic cell sarcoma is a malignant tumor of the follicular
dendritic cell which can arise in extranodal sites. We present here a case
arising as a mass in the breast of a 41-year-old woman. The tumor was composed of
mildly pleomorphic spindly cells with pale ovoid nuclei and cell processes
intimately admixed with mature lymphocytes. In much of the lesion the cells were
dispersed in cords in a myxoid stroma, and elsewhere there were solid sheets. The
neoplastic cells were immunoreactive for CD21, CD35, EMA, and S100 protein, but
not for other lymphoid markers or cytokeratin. Electron microscopy showed
interdigitating cytoplasmic processes with junctions but no external lamina. The
differential diagnosis includes carcinoma, lymphomas, and a variety of myxoid
sarcomas. The tumor recurred within a few months and displayed increased nuclear
pleomorphism and lymphatic invasion but the patient appears free of disease 3
years after the further excision. This case extends the spectrum of follicular
dendritic cell sarcoma in soft tissue sites.
PMID- 10196390
TI - Pseudosarcoma in Paget's disease of bone.
AB - The appearance of a sarcoma of bone is a well-recognized complication of Paget's
disease. The most common type of such a sarcoma is osteosarcoma. Much less common
are soft tissue lesions adjoining the pagetic bone that clinically and
radiologically simulate sarcoma but histologically represent exaggerated
periosteal bone formation as a manifestation of the basic pathologic process. We
present a case of a bulky juxtacortical soft tissue mass in the thigh arising
from a pagetic femur in a 62-year-old patient with polyostotic Paget's disease
that was clinically and radiologically suspected to be a juxtacortical
osteosarcoma. Microscopically, the lesion showed features of florid Paget's
disease without any evidence of sarcomatous growth. It is important to be aware
of this rare manifestation of Paget's disease to avoid unnecessary overtreatment.
PMID- 10196391
TI - Practical applications of immunohistochemistry in hematolymphoid neoplasms.
AB - Immunohistochemistry plays a key role in the diagnosis and classification of
hematolymphoid neoplasms. New cell and lineage markers are constantly being
discovered and added to the existing long list of antibodies. In this review
article we provide general information and new applications of the commonly used
hematolymphoid markers. We also discuss the features and applications of some
newly discovered markers, such as ALK, fascin, granzyme/perforin, and tryptase.
There is no universal "panel" for the diagnosis of hematolymphoid neoplasms.
However, in this review article, we provide suggested panels for a given
hematolymphoid neoplasm that is based on our experience and that reported in the
literature.
PMID- 10196392
TI - The "Gnomes": An adventure in hepatopathology.
AB - The "Gnomes" are an international group of liver pathologists and clinicians
interested in liver morphology. The group was founded 30 years ago in an attempt
to clarify the confusing concepts of chronic hepatitis that were then prevalent.
Its first slide circulation and meeting resulted in the 1968 classification of
chronic hepatitis. Recognizing the potential fruitfulness of the group, the
members continued to meet for 2 or 3 days each year to discuss a variety of
topics. The group has published nine reports that include guidelines for
pathologists on different aspects of liver disease. Its membership has changed
over the years, but many of the founding members continue to take part in the
annual discussions.
PMID- 10196393
TI - Drs chalk and cheese: A tale of two surgical pathologists
PMID- 10196394
TI - Radiation therapy treatment optimization. Introduction.
PMID- 10196395
TI - Managing geometric uncertainty in conformal intensity-modulated radiation
therapy.
AB - The geometric precision of radiotherapy treatments must increase if the
objectives of dose escalation and increased disease control are to be achieved.
There are multiple strategies for increasing the geometric precision of a
radiotherapy treatment system, including immobilization and setup aids for
reducing random and systematic components of setup errors and organ motion alike.
Alternatively, more complex strategies can be implemented based on additional
information acquired over the course of treatment. Generally, these strategies
can be divided into two categories: off-line and on-line. The strategies that are
implemented in the clinic must consider the required geometric precision for a
given treatment. From this specification, it is possible to select the
appropriate strategies and approaches. The cost associated with each approach
must also be considered. Once a system for delivery has been designed, the
residual uncertainties must still be considered in the planning process. Parallel
to the development of strategies for reducing uncertainty, progress is being made
in better relating these residual uncertainties to margins for use in treatment
planning. This article reviews advances in reducing uncertainty.
PMID- 10196396
TI - Optimized planning using physical objectives and constraints.
AB - Intensity-modulated radiation therapy (IMRT) allows one to achieve a better
conformation of the high-dose region to the prescribed tumor target volume than
uniform beam therapy, especially in complex treatment situations. Still, perfect
conformation is impossible. Hence the goal of optimized IMRT planning or inverse
planning is to find the beam profiles that yield the optimum among the physically
achievable treatment plans. The principal physical advantage of IMRT is best
exploited if the optimization is driven by physical criteria. This article
presents an overview of such physical, yet clinically relevant, criteria along
with optimization algorithms that take these criteria into account. Practical
computer implementations are described, which allow one to perform the
optimization in an interactive manner within a few minutes. The application of
these methods to some complex clinical example cases is presented, and the
results are compared with uniform beam treatment plans and with biologically
optimized plans.
PMID- 10196397
TI - Optimized radiation therapy based on radiobiological objectives.
AB - In the broad field of radiation therapy optimization, both simple and complex
problems have their origins in the interaction of the radiation beams with the
biological structures of normal and malignant tissues of the human body.
Therefore, it is no great surprise that many treatment optimization problems are
best handled by the use of well-designed radiobiological models. The classic way
of quantifying dose-response relations for tumors and normal tissues as well as
their cross-correlation with each other and their dependence on the underlying
genetic and molecular biology of the cell are first briefly reviewed.
Radiobiological objective functions, such as the probability of achieving
complication-free cure and its expectation value under influence of stochastic
processes during the course of treatment, are defined and shown to solve many of
the problems of radiation therapy planning. Finally, it is shown through the use
of these quantifiers that, simply by introducing biologically optimal intensity
modulated dose delivery, the treatment outcome can be improved by about 20% or
more in cases with a complex spread of the disease. Once radiobiological optimal
plans have been developed, they can be approximated by ordinary physical
planning, but the biological objective functions are still needed to have a
figure of merit for the quality of the treatment.
PMID- 10196398
TI - Intensity-modulated radiation therapy with dynamic multileaf collimators.
AB - Intensity-modulated radiotherapy (IMRT) has been considered as a means of
providing dose distributions that conform to concave target volumes. For computer
controlled multileaf collimators (MLCs) to be used to modulate x-ray beams, some
procedure must be used to determine the sequence of leaf positions used to
produce the desired modulation. This article derives and compares four leaf
sequencing algorithms. MLC leaf sequencing can be accomplished by representing
the areal intensity modulation of a beam with a series of beam profiles. A
velocity-modulation equation for computing the modulation required for a one
dimensional profile, described originally using more extensive algebra, is
derived using a graphic approach. The velocity-modulation approach is compared
with an equal incremental step-and-shoot approach derived by Bortfeld and Boyer.
An areal step-and-shoot technique derived by Xia and Verhey is introduced and
compared with the profile-by-profile methods. Finally, an approach is considered
using multiple repeated arcs developed by Yu. This wide variety of methods can
yield an approach to IMRT that conforms to the engineering constraints imposed by
the design of a particular linear accelerator.
PMID- 10196399
TI - Optimization and clinical use of multisegment intensity-modulated radiation
therapy for high-dose conformal therapy.
AB - Intensity-modulated radiation therapy (IMRT) may be performed with many different
treatment delivery techniques. This article summarizes the clinical use and
optimization of multisegment IMRT plans that have been used to treat more than
350 patients with IMRT over the last 4.5 years. More than 475 separate clinical
IMRT plans are reviewed, including treatments of brain, head and neck, thorax,
breast and chest wall, abdomen, pelvis, prostate, and other sites. Clinical
planning, plan optimization, and treatment delivery are summarized, including
efforts to minimize the number of additional intensity-modulated segments needed
for particular planning protocols. Interactive and automated optimization of
segmental and full IMRT approaches are illustrated, and automation of the
segmental IMRT planning process is discussed.
PMID- 10196400
TI - Comparison of three-dimensional conformal radiation therapy and intensity
modulated radiation therapy systems.
AB - The use of three-dimensional conformal radiation therapy (3DCRT) has now become
common practice in radiation oncology departments around the world. Using beam's
eye viewing of volumes defined on a treatment planning computed tomography scan,
beam directions and beam shapes can be selected to conform to the shape of the
projected target and minimize dose to critical normal structures. Intensity
modulated radiation therapy (IMRT) can yield dose distributions that conform
closely to the three-dimensional shape of the target volume while still
minimizing dose to normal structures by allowing the beam intensity to vary
across those shaped fields. Predicted dose distributions for patients with tumors
of the prostate, nasopharynx, and paraspinal region are compared between plans
made with 3DCRT programs and those with inverse-planned IMRT programs. The IMRT
plans are calculated for either static or dynamic beam delivery methods using
multileaf collimators. Results of these comparisons indicate that IMRT can yield
significantly better dose distributions in some situations at the expense of
additional time and resources. New technologies are being developed that should
significantly reduce the time needed to plan, implement, and verify these
treatments. Current research should help define the future role of IMRT in
clinical practice.
PMID- 10196401
TI - Clinical and financial issues for intensity-modulated radiation therapy delivery.
AB - Intensity-modulated radiation therapy (IMRT) is a term applied to a new
technology that uses nonuniform radiation beams to achieve conformal dose
distributions. This article reviews the use of a commercial system, the Peacock
system, which uses a special multileaf collimator (MIMiC) to deliver the dose
distribution using arc therapy and segmented fields, similar to a moving strip.
Although initially designed for stereotactic radiosurgery, this system has been
employed to treat various body sites. More than 300 patients have been treated at
our institution in the past 4 years, mainly for cranial, head-and-neck, and
prostate tumors. Presently, we treat 40 to 45 patients per day with this
technology using two linear accelerators operating with 10 MV and 15 MV x-rays,
as Peacock has become a standard therapy procedure. Cases are presented that show
the unique ability of IMRT to deliver conformal dose distributions. Why this type
of technology can become a standard procedure and why it is cost-effective
therapy for both the institution and the patient are discussed.
PMID- 10196402
TI - Tomotherapy.
AB - Tomotherapy is delivery of intensity-modulated, rotational radiation therapy
using a fan-beam delivery. The NOMOS (Sewickley, PA) Peacock system is an example
of sequential (or serial) tomotherapy that uses a fast-moving, actuator-driven
multileaf collimator attached to a conventional C-arm gantry to modulate the beam
intensity. In helical tomotherapy, the patient is continuously translated through
a ring gantry as the fan beam rotates. The beam delivery geometry is similar to
that of helical computed tomography (CT) and requires the use of slip rings to
transmit power and data. A ring gantry provides a stable and accurate platform to
perform tomographic verification using an unmodulated megavoltage beam. Moreover,
megavoltage tomograms have adequate tissue contrast and resolution to provide
setup verification. Assuming only translational and rotational offset errors, it
is also possible to determine the offsets directly from tomographic projections,
avoiding the time-consuming image reconstruction operation. The offsets can be
used to modify the leaf delivery pattern to match the beam to the patient's
anatomy on each day of a course of treatment. If tomographic representations of
the patient are generated, this information can also be used to perform dose
reconstruction. In this way, the actual dose distribution delivered can be
superimposed onto the tomographic representation of the patient obtained at the
time of treatment. The results can be compared with the planned isodose on the
planning CT. This comparison may be used as an accurate basis for adaptive
radiotherapy whereby the optimized delivery is modified before subsequent
fractions. The verification afforded tomotherapy allows more precise conformal
therapy. It also enables conformal avoidance radiotherapy, the complement to
conformal therapy, for cases in which the tumor volume is ill-defined, but the
locations of sensitive structures are adequately determined. A clinical
tomotherapy unit is under construction at the University of Wisconsin.
PMID- 10196403
TI - Medicolegal issues: headache.
AB - This article addresses headache-related topics in which medicolegal issues have
occurred or in which they are likely to occur. Where possible, an actual case has
been presented. Most sections of this article are divided into three parts:
principle of care, case history, and discussion and recommendations. When
appropriate, American Academy of Neurology guidelines have been noted.
PMID- 10196404
TI - Medical-legal aspects of sleep medicine.
AB - Sleepiness and sleep disorders are increasingly raising interesting and important
medical-legal issues in three areas: violent or injurious behavior arising from
the sleep period, accidents or errors in judgment caused by sleepiness behind the
wheel or in the workplace, and disability determinations caused by sleepiness
induced work impairment. Sleep-related violence may be caused by many conditions,
most of which are diagnosable and treatable. Legal issues raised by these
behaviors are usually enigmatic. The nature of such behaviors may be extremely
complex, and documenting that a given violent act was caused by such a behavior,
after the fact, may be difficult. Guidelines for the medical-legal evaluation of
such behaviors have been developed and are evolving. Culpability determination in
sleepiness-related industrial or motor vehicle accidents is in the developmental
stage, and varies by jurisdiction. Disability determination for workplace
sleepiness caused by sleep disorders is in its infancy, and poses a challenge,
given the erroneous but pervasive societal attitude that sleepiness is a
manifestation of laziness, depression, sloth, work-avoidance behavior, or a
defect of character.
PMID- 10196405
TI - Legal aspects of epilepsy.
AB - This article discusses issues of concern for physicians who treat patients with
epilepsy. It particularly focuses on driving laws and employment of people with
epilepsy. Physicians are often asked to provide certification to state driving
authorities regarding whether their patients are fit to drive; sometimes, they
are required to report patients who experience seizures to the state. Potential
liability areas for physicians are also discussed in this article. In addition,
this article addresses the increasing importance of the physician's role in
determining whether a person who has seizures can perform certain jobs safely,
and discusses approaches the physician can take to assist employers in providing
reasonable accommodations for people with epilepsy.
PMID- 10196406
TI - Violence and the epilepsy defense.
AB - The essence of the epilepsy defense is the argument that a crime was committed as
a result of the perpetrator having epilepsy, and thus that he or she should not
be held responsible for a violent crime. Neurologists are frequently asked to
pass judgment regarding whether an alleged act may have been the result of an
epileptic condition; therefore, neurologists should be informed as to what
criteria should be used to decide if a given act was, or could have been, the
result of an epileptic seizure. This article discusses three cases where epilepsy
is used as the defense argument. In addition, this article reviews types of
epileptic seizures, syncopal events, and pseudoseizures.
PMID- 10196407
TI - Selected legal issues in movement disorders.
AB - This article explores the long-standing question of whether trauma causes
Parkinson's disease, and discusses the impact of informed consent and
confidentiality in issues of genetic testing for Huntington's disease.
Neurologists are appropriately concerned about the legal aspects of genetic
testing, and this article attempts to address that subject from a medical-legal
perspective.
PMID- 10196408
TI - Approach to neurotoxicity tort cases.
AB - This article provides the neurologist with simple methods that can be applied to
all clinical neurologic evaluations, regardless of the future potential for
litigation. This article defines the appropriate application and interpretation
of conventional neurologic, neurophysiologic, neuropsychological, and biochemical
diagnostic tests that are sensitive to neurotoxic exposures. This article also
provides the neurologist with guidance in the preparation of clinical findings
and tips on the recognition and use of supportive literature that is often
required for admissibility of evidence at a deposition or testimony.
PMID- 10196409
TI - The neurologically impaired child and alleged malpractice at birth.
AB - Controlled studies, improved epidemiologic and statistical techniques, and an
increase in biological information on mechanisms of fetal and neonatal brain
injury or maldevelopment have led to a better, although still imperfect,
understanding of the cause of developmental disabilities. The role of asphyxia
during the birth process is smaller than was once believed. Intrauterine exposure
to infection, autoimmune and coagulation disorders, and problems specific to
multiple pregnancies are risk factors for cerebral palsy. Electronic fetal
monitoring and other observations during birth are unsatisfactory management
guides, having enormously high rates of false-positive identification. There is
no evidence that caesarean section can prevent cerebral palsy in term infants.
PMID- 10196410
TI - Brain death.
AB - Current law in the United States authorizes physicians to diagnose brain death by
applying generally accepted neurologic criteria for determining loss of function
of the entire brain. This article offers a medical-legal perspective on problems
that may arise with respect to the determination of brain death. These include
the possibility of diagnostic error, conceptual disagreements that may constrain
the use of neurologic criteria to diagnose death, and the conflation of brain
death and loss of consciousness. This article also addresses legal aspects of the
debate over whether to expand the definition of brain death to include permanent
unconsciousness. Although existing laws draw a clear distinction between brain
death and the persistent vegetative state, many courts have authorized removal of
life support from individuals whose unconsciousness is believed to be permanent
on proof that removal accords with preferences expressed before sentience was
lost.
PMID- 10196411
TI - Medical records confidentiality.
AB - Laws defining the physician's duty of confidentiality vary from state to state.
Legal and ethical requirements may not be the same for all specialties. Advances
in information technology threaten the patient's right to medical records'
privacy. Physicians must take the lead in preserving that right.
PMID- 10196412
TI - Managed care liability: what is the proper remedy?
AB - This article discusses current state and federal regulations regarding managed
care liability. Significant statutory reform is the proper remedy for consumers
and individually practicing physicians who are now confronted with objectionable
managed care organization behavior and practices. Other possible reforms to the
current statutes regarding managed care organizations and their practices are
also discussed in this article.
PMID- 10196413
TI - Health care fraud.
AB - The term health care fraud describes a variety of sins committed with more
frequency and sophistication by a multitude of sinners. Because physicians are
among those most likely to be affected by such fraud and efforts to prevent it,
they may want to be familiar with this subject. Accordingly, certain aspects of
health care fraud are reviewed from a physician's perspective.
PMID- 10196414
TI - Introduction to notification, deposition, and court testimony: A primer for the
defendant physician.
AB - Knowledge of legal mechanisms in a medical malpractice case is the defendant
physician's power. Truth cannot be compromised; however, information can be
displayed in the best light, which requires intense preparation, the best
predictor of a successful case presentation.
PMID- 10196415
TI - Neurologic malpractice: the perspective of a patient's lawyer.
AB - The definition of professional negligence is clearer than is commonly believed.
Trials rarely involve lack of informed consent. In fact, the main dispute at a
trial usually concerns what really happened. Causation, however, is the prime
area of disagreement between the experts. The trial judge and the appeals court
are required to set aside a jury verdict that is without proper legal basis,
either regarding liability or the amount awarded. The best screen against
unjustified lawsuits is a knowledgeable plaintiff's attorney aided by a competent
expert review.
PMID- 10196416
TI - Expert witness testimony: A trial judge's perspective.
AB - This article discusses the use of expert, scientific testimony in Judge
Weinstein's courtroom cases that involved Agent Orange, silicone breast implants,
repetitive stress injuries, diethylstilbestrol (DES), and asbestos. The author
summarizes the evidentiary standards for admitting expert, scientific testimony,
and discusses some of the unique ethical and logistical issues presented by such
evidence. Advice is offered for prospective expert witnesses. Possible solutions
to the problems the legal and scientific communities face in balancing society's
need for expert evidence and its limitations are addressed.
PMID- 10196417
TI - Expert witness testimony: An update.
AB - This update provides an overview of the current state of expert witness testimony
regarding malpractice cases. Many trials are reduced to a battle of the experts
and many physicians advertise their credentials and expertise in hopes of
attracting lucrative cases. This article focuses on what constitutes an expert
witness, medical organizations oversight, the peer review process, and physician
immunity.
PMID- 10196418
TI - Documentation and informed consent.
AB - Documentation remains the key factor that leads to success or failure of a claim
in a significant number of cases. Since the time of a trial is often years later,
an accurate memory can only be reflected by the records kept by the physician in
question. This article focuses on developing good habits of documentation in
areas such as medical record maintenance, handwriting, informed consent, and
record tampering. Guidelines for improved record keeping are also presented in
this article.
PMID- 10196419
TI - Malpractice or maloccurrence: A detailed analysis of two cases.
AB - Sometimes neurologists face malpractice suits that occur from cases when a
patient's diagnosis is not foreseeable. This requires that neurologists make
clear and accurate notes on patient charts to show current reasoning in
expectation that eventually, the neurologist may have to defend his or her
misdiagnosis in court. Two current trial cases are presented in this article. You
decide, which case should be considered malpractice or maloccurrence?
PMID- 10196420
TI - Epidemiology: hip and knee.
AB - This article reviews the epidemiologic features of periprosthetic fractures
around total hip arthroplasty and total knee arthroplasty according to the site
of fracture occurrence. The frequency and cause of intraoperative and
postoperative periprosthetic fractures vary by anatomic site. For each anatomic
site, unique risk factors, some demographic and some technical, appear to be
related to risk of fracture. For several anatomic sites, excellent articles that
collate large numbers of series are available to the reader to provide aggregate
information concerning the epidemiology of these fractures.
PMID- 10196421
TI - The prevention of periprosthetic fractures in total hip and knee arthroplasty.
AB - Periprosthetic fractures in total hip and total knee arthroplasty lead to
considerable morbidity in terms of component fixation, bone loss, and subsequent
function. The management of these fractures is technically demanding and may
result in suboptimal fixation owing to poor bone stock. The prevention, early
recognition, and appropriate management of such fractures are therefore critical.
The pathogenesis of periprosthetic factors is multifactorial. There are a number
of intrinsic patient influences such as bone stock, biomechanics, and compliance.
There are also a host of extrinsic factors over which the surgeon has more
control. The prevention of periprosthetic fractures requires careful preoperative
planning and templating, the availability of the necessary expertise and
equipment, and knowledge of the potential pitfalls so that these can be avoided
both intraoperatively and in follow-up.
PMID- 10196422
TI - Classification of periprosthetic fractures complicating total knee arthroplasty.
AB - As the total number of knee arthroplasties increase, the frequency with which
periprosthetic fractures will be encountered can be expected to increase as well.
The classification of these fractures is an important aspect in the development
of an understanding of these problems. Adequate classification systems allow
accurate communication between researchers and comparisons to be made between
different techniques. Classification systems also allow algorithms to be
developed to guide clinicians in the diagnosis, investigation, and treatment of
these fractures. The authors present an outline of the classification systems
described for fractures occurring in relation to total knee arthroplasty.
PMID- 10196423
TI - Classification of the hip.
AB - A number of classification systems have been proposed for periprosthetic
fractures of the femur following total hip replacement. Most of these rely purely
on the site and pattern of the fracture. However, it is only after consideration
of other important factors, including the stability of the prosthesis as well as
the quality of the surrounding bone stock, that appropriate management can be
instituted. The authors have developed a new classification system that addresses
these other important factors. The authors believe that only after classifying a
periprosthetic fracture with specific reference to fracture site, stability of
the implant, and quality of the surrounding bone stock, can one make a rational
decision towards a treatment algorithm.
PMID- 10196424
TI - Periprosthetic fractures of the acetabulum.
AB - Periprosthetic acetabular fractures during and after total hip replacement occur
infrequently. Intraoperative fractures have risen with the use of press fit
cementless fixation techniques and postoperative fractures are increasing because
of the long-term problems associated with osteolysis. This article outlines the
classification and management of these fractures.
PMID- 10196425
TI - Fractures of the femur after hip replacement: the Oregon experience.
AB - The article provides an analysis of 102 interventions in 93 periprosthetic
fractures of the femur contributed by multiple surgeons predominately in
community practice. The authors find that treatment of periprosthetic fracture of
the femur is problematic. Success in terms of arthroplasty function and fracture
treatment is difficult to achieve. Specific treatment recommendations are made
based upon the success and failures of this survey.
PMID- 10196426
TI - The treatment of periprosthetic fractures of the femur using cortical onlay
allograft struts.
AB - Periprosthetic fractures of the femur are a complex problem to treat. Careful
planning is essential before embarking on such a technically demanding procedure.
There are many factors to be considered, including the premorbid condition of the
patient and previous experience and training of the surgeon. Important factors
relating directly to the fracture include the site, stability of the implant, and
the state of the surrounding bone stock.
PMID- 10196427
TI - The use of structural allografts for treating periprosthetic fractures about the
hip and knee.
AB - When a periprosthetic fracture about the knee or hip is associated with segmental
bone loss and a loose implant, a structural allograft may be indicated. The
implant is cemented into the allograft but not into the host. The host graft
junction is stabilized by the long stem of the implant and a step-cut osteotomy.
The junction can be further reinforced by cortical strut allograft and residual
host bone with soft tissues still attached to enhance union. Once the host bone
unites to the allograft, the reconstruction is stabilized.
PMID- 10196428
TI - Periprosthetic fractures of the femur complicating total knee arthroplasty.
AB - Fractures of the femur in the presence of a total knee arthroplasty may occur
intraoperatively or postoperatively. Management of these fractures is often
challenging because of a variety of factors, including those related to the
fracture itself, and the quality of the bone, prosthesis, and patient. Treatment
options include nonoperative methods, reduction and internal fixation, and
revision of the arthroplasty. Complications of treatment are not uncommon and may
be severe. These issues are discussed in the article.
PMID- 10196429
TI - Total knee arthroplasty: periprosthetic tibial fractures.
AB - A classification for periprosthetic tibial fractures is presented. It is based on
the anatomic location of the fracture in reference to the tibial component;
whether the fracture occurred during surgery or in the postoperative period; and
whether the prosthesis is radiographically well-fixed or loose. A treatment
algorithm is proposed for each fracture type.
PMID- 10196430
TI - Fractures of the patella after total knee replacement.
AB - Pateller fractures in association with total knee replacement are uncommon, but
potentially a cause of an unsatisfactory clinical outcome. Patient, implant, and
technical factors are important predisposing causes of these patellar fractures.
Prevention is the best treatment. Important outcome criteria include the
integrity of the extensor mechanism, patellar implant fixation, and anatomic
location. Patients requiring operative intervention often have an unsatisfactory
outcome.
PMID- 10196431
TI - Knee: role and results of allografts.
AB - The vast majority of periprosthetic fractures occur as the result of trauma.
There are many predisposing factors for these factors, including osteopenia,
neurologic disorders, medications, rheumatoid arthritis, previous arthroplasty,
and infection. These same factors also increase the likelihood of fracture
comminution, and the presence of poor bone quality makes fixation difficult and
prone to failure.
PMID- 10196432
TI - Periprosthetic fractures of the humerus and scapula: management and prevention.
AB - The management of humerus fractures is complicated by the presence of a
prosthesis. Vigilance in addressing the mechanisms and predisposing factors for
periprosthetic fracture may prevent their occurrence. In the event of a
periprosthetic fracture, attention to prosthetic stability, fracture location and
stability, and bone quality will help guide treatment decisions. Treatment should
be commensurate with the goals of fracture stability, early rehabilitation, and
maintaining a well-functioning prosthesis.
PMID- 10196433
TI - Periprosthetic fractures about the elbow.
AB - As total elbow replacements are being performed more frequently, more
periprosthetic fractures are occurring. Although this is a frequent topic of
discussion for hips and knees, the literature contains little information to
guide treatment of such fractures around the elbow. This article outlines the
principles of classification and treatment based on the authors' clinical
experience with more than 1000 total elbow arthroplasties.
PMID- 10196434
TI - Septorhinoplasty. Form versus function.
AB - Septorhinoplasty is the most difficult and complicated procedure in facial
plastic surgery. Because of the complex interdependency of the anatomical parts,
alteration of one may have an impact on another. Three-dimensional relationships
are important, as is the maintenance of a proper framework for the internal and
external nose. Form and function are completely interwoven in septorhinoplasty.
PMID- 10196435
TI - Considerations before rhinoplasty.
AB - Patient evaluation and selection for aesthetic facial surgery and rhinoplasty in
particular goes beyond assessment of anatomical indications. The selection of
appropriate candidates involves an understanding of the patient's motivations for
the procedure, expectations for the surgical outcome, and ego strength for
tolerating the stress of operative intervention. The patient interview must be
structured to give the surgeon ample information to determine the psychological
and emotional stability of the candidate. Psychiatric consultation may be
required if evidence is uncovered indicating psychiatric illness. Time spent
informing the patient preoperatively will pay off great dividends in the
postoperative period. If patient dissatisfaction does occur, validate and address
the patient's concerns with a nondefensive posture.
PMID- 10196436
TI - The septum in rhinoplasty.
AB - Recognition and correction of septal abnormalities in rhinoplastic surgery has
been a constant evolution aided by the development of an in depth anatomic
understanding of the nose and the refinement of techniques based on the pertinent
anatomy. Whether the deformity presents a functional, aesthetic, or combined
problem, the authors prefer a single stage technique that separates the
structural components of the nose, isolating the deformities present, and then
reconstructing the components to effect a desirable result in terms of airway and
appearance. Although no two nasal surgeries are identical, there are
characteristic deformities that are noted to be generally more problematic. We
briefly review normal septal anatomy as it pertains to the septorhinoplasty
operation and then discuss our approach to specific septal variations that we
have found to have a significant impact with regard to achieving satisfactory
functional and aesthetic results.
PMID- 10196437
TI - Functional nasal surgery.
AB - Functional nasal surgery is designed to repair nasal obstruction frequently
caused by previous reduction rhinoplasty or blunt nasal trauma. Distinguishing
the statically narrowed nasal valve from the weak sidewall with dynamic collapse
is an important part of the preoperative evaluation. Our workhorse for repair of
static obstruction is the combination of spreader grafts and flaring sutures,
which together create a significant increase in the intranasal valve area.
Dynamic collapse of the sidewall is corrected with cartilaginous batten grafts
designed to increase sidewall rigidity. Less common causes of valve obstruction,
such as tip ptosis, facial paralysis, cicatricial stenosis, Mohs reconstruction,
and paradoxical lateral crura, are repaired by more individualized techniques.
PMID- 10196438
TI - Repairing the twisted nose.
AB - Correction of the deviated nose presents a challenge to even the experienced
rhinoplastic surgeon. This article describes the etiology, analysis, and surgical
treatment for the severely twisted nose. The applied anatomy of the deviated nose
is discussed in detail. Finally, a graduated approach to surgical management is
described.
PMID- 10196439
TI - Deprojecting the nasal profile.
AB - The nose is the most prominent aesthetic feature of the facial profile. Nasal
length, tip rotation, and tip projection are integral aspects in analysis of the
nasal profile. In most rhinoplasties the surgeon has the difficult task of
increasing or maintaining tip projection of an underprojected or normally
projected nasal tip. Less commonly, the rhinoplastic surgeon is presented with an
overprojected nasal tip, and efforts are focused on deprojecting the nasal
profile. In this article, the authors present a discussion of the overprojected
tip, elucidating strategies of analysis, etiologies, and management of the nasal
profile and give clinical examples.
PMID- 10196440
TI - Architectural deficiencies of the nose: treatment of the saddle nose and short
nose deformities.
AB - The saddle nose and short nose deformities are challenging surgical problems
characterized by significant architectural deficiencies of the nasal framework.
These defects produce cosmetic and functional nasal problems. Reconstructive
techniques and augmentation materials are reviewed. Case examples illustrate the
authors currently preferred techniques.
PMID- 10196442
TI - Special article
PMID- 10196441
TI - Grafts amd implants in rhinoplasty and nasal reconstruction.
AB - The quest for nasal symmetry and balance with the face often mandates the need
for implantable materials to sculpt and rebuild the nasal skeleton and the
overlying tissues. A suitable implant must be biocompatible, strong, and elastic.
Implant materials that may be used in the nose can be divided into four groups:
autografts, homografts, xenografts, and alloplasts. Each type of implant is
reviewed and discussed in the context of rhinoplasty and nasal reconstruction.
PMID- 10196443
TI - Surgical anatomy of the nose
AB - It is imperative to know the details of the anatomy of the nose before
understanding any surgical procedure performed on the nose. The details presented
in this article should help the experienced and the novice surgeon accomplish the
difficult task of a rhinoplasty.
PMID- 10196444
TI - Role of carbon monoxide in L-glutamate-induced cardiovascular responses in
nucleus tractus solitarius of conscious rats.
AB - Heme oxygenase degrades heme to form carbon monoxide. It has been reported that
heme oxygenase-derived carbon monoxide may interact with L-glutamate (L-Glu)
receptors in the nucleus tractus solitarius (NTS). Integrative studies suggest
that heme oxygenase inhibitors raise blood pressure, in part, by inhibiting
carbon monoxide formation in the NTS. The currents studies were designed to
determine if heme oxygenase inhibitors affect the cardiovascular actions of L-Glu
in the NTS. Accordingly, MAP and HR responses to unilateral microinjections of L
Glu (5 nmol/100 nl) into the NTS were measured before and after ipsilateral
microinjections of zinc deuteroporphyrin 2,4-bis glycol (ZnDPBG, 4.5 nmol/100 nl)
or chromium mesoporphyrin (CrMP, 1.5 nmol/100 nl) in awake rats chronically
instrumented with NTS guide cannulaes and arterial catheters. With respect to non
treatment (+36+/-5 mmHg, -107 bpm, n=10), ZnDPBG pre-treatment attenuated the
pressor and bradycardic responses to L-Glu (+7+/-3 mmHg, -10+/-6 bpm, P<0.05).
CrMP similarly attenuated cardiovascular responses to L-Glu (+47+/-3 mmHg, -68+/
8 bpm vs. +20+/-5 mmHg, -40+/-9 bpm; before vs. after, n=10, P<0.05). Matched
series yielded no vehicle- or time-related effects. Our findings suggest that a
heme oxygenase product, such as carbon monoxide, may affect NTS glutamatergic
neurotransmission to participate in cardiovascular control.
PMID- 10196445
TI - Transient increase of synapsin-I immunoreactivity in the mossy fiber layer of the
hippocampus after transient forebrain ischemia in the mongolian gerbil.
AB - Synapsin-I is a vesicular phosphoprotein, which regulates neurotransmitter
release, neurite development, and maturation of synaptic contacts during normal
development and following various brain lesions in adulthood. In the present
study, we have examined by immunohistochemistry possible modifications in the
expression of synapsin-I in the hippocampus of Mongolian gerbils after transient
forebrain ischemia. The animals were subjected to 5 min of transient forebrain
ischemia through bilateral common carotid occlusion, and were examined at
different time-points post-ischemia. Transient forebrain ischemia produces cell
death of the majority of CA1 pyramidal neurons of the hippocampus and polymorphic
hilar neurons of the dentate gyrus. This is followed by reactive changes,
including synaptic reorganization and modifications in the expression of synaptic
proteins, which provide the molecular bases of synaptic plasticity. Transient
decrease of synapsin-I immunoreactivity was observed in the inner zone of the
molecular layer of the dentate gyrus, thus suggesting denervation and posterior
reinervation in this area. In addition, a strong increase in synapsin-I
immunoreactivity was observed in the hilus of the dentate gyrus and in the mossy
fiber layer of the hippocampus at 2, 4 and 7 days after ischemia. Parallel
increases in synaptophysin immunoreactivity were not observed, thus suggesting a
selective induction of synapsin-I after ischemia. The present results indicate
that synapsin-I participates in the reactive response of granule cells to
transient forebrain ischemia in the hippocampus of the gerbil, and suggest a role
for this protein in the plastic adaptations of the hippocampus following injury.
PMID- 10196446
TI - Modulation of rhythmic melatonin synthesis in Xenopus retinal photoreceptors by
cyclic AMP.
AB - Cyclic AMP regulates melatonin synthesis in vertebrate photoreceptor cells. In
the present study, we investigated whether the circadian rhythm of melatonin
synthesis in Xenopus retinal photoreceptor layers is driven by rhythmic changes
in cyclic AMP. When the photoreceptor layers were continuously treated with 8-(4
chlorophenylthio)-cyclic AMP (8-CPT-cAMP) at a saturating concentration (1 mM),
melatonin release was increased at all times of the day, but robust melatonin
rhythms were maintained for 2 days in constant darkness (DD). We also measured
cyclic AMP efflux and melatonin release simultaneously from photoreceptor layers
that were continuously treated with forskolin and/or 3-isobutyl-1-methylxanthine
(IBMX) in light-dark (LD) and DD. Circadian rhythmicity was observed in melatonin
release, but not in cyclic AMP efflux, suggesting that changes of melatonin
levels are not always caused by the changes of the cyclic AMP levels. In
addition, the simultaneous treatment of forskolin and IBMX appeared to saturate
sensitivity of melatonin synthesis to cyclic AMP, but this treatment did not
abolish melatonin rhythms. These results suggest that circadian rhythms of
melatonin can be driven without rhythmic changes of cyclic AMP, and that cyclic
AMP regulates melatonin in parallel with the output pathways from the circadian
oscillator.
PMID- 10196447
TI - Mechanism of the kainate-induced intracellular acidification in leech Retzius
neurons.
AB - We examined the effect of the glutamatergic agonist kainate on the membrane
potential, the intracellular Na+ concentration ([Na+]i), the intracellular-free
Ca2+ concentration, and on the intracellular pH of Retzius neurons of the
medicinal leech, Hirudo medicinalis, in order to investigate the mechanism
responsible for the intracellular acidification caused by glutamatergic
stimulation. The recordings were made with Na+- and pH-sensitive microelectrodes
and iontophoretically injected Fura-2. Bath application of kainate evoked a
marked membrane depolarization, a [Na+]i increase, and an intracellular
acidification. The intracellular acidification was unaffected by reversal of the
electromotive force for H+, suggesting that an influx of H+ from the interstitial
space does not contribute to the acidification. While the Ca2+ channel blockers
La3+ and Co2+ had no effect on the kainate-induced intracellular acidification,
suggesting that a Ca2+ influx via voltage-dependent Ca2+ channels was not
relevant, the acidification was reduced in Ca2+-free saline solution. In Na+-free
saline solution the kainate-induced intracellular acidification was absent,
suggesting the involvement of Na+ influx in generating the acidification. When
injected iontophoretically Na+ induced an intracellular acidification but Li+,
K+, Rb+ or Cs+ did not. Furthermore, a [Na+]i increase induced by blocking the
Na+/K+ pump also led to an intracellular acidification. We conclude that the
[Na+]i increase is the crucial event underlying the kainate-induced intracellular
acidification. Possible mechanisms linking the [Na+]i increase to the
intracellular acidification are discussed.
PMID- 10196448
TI - Comparison of touch- and laser heat-evoked cortical field potentials in conscious
rats.
AB - Field potentials and multiunit activities from chronically implanted cortical
electrodes were used to study tactile and nociceptive information processing from
the tail of the rat. Fourteen stainless steel screws implanted in the skull were
used as electrodes to record field potentials in different cortical areas.
Electrical, mechanical, and laser pulses were applied to the tail to induce
evoked cortical field potentials. Evoked responses were compared before and after
sodium pentobarbital anesthesia (50 mg/kg, i.p.). In both electrical- and
mechanical-evoked potential (EEP and MEP) studies, two major peaks were found in
the conscious animal. The polarity of the late component was modified after
pentobarbital anesthesia. In the laser-evoked potential (LEP) study, two distinct
negative peaks were found. Both peaks were very sensitive to anesthesia.
Following quantitative analysis, our data suggest that the first positive peak of
EEP and MEP corresponded to the activation of the Abeta fiber, the second
negative peak of MEP and the first peak of LEP corresponded to Adelta fiber
activation, while the second peak of LEP corresponded to C fiber activation. The
absolute magnitudes of all cortical components were positively related to the
intensity of the stimulation. From spatial mapping analysis, a localized
concentric source of field potential was observed in the primary somatosensory
cortex (SI) only after activation of the Abeta fiber. Larger responsive cortical
areas were found in response to Adelta and C fiber activation. In an
intracortical recording experiment, both tactile and nociceptive stimulation
evoked heightened unit activity changes at latencies corresponding to respective
field potentials. We conclude that different cortical areas are involved in the
processing of A and C fiber afferent inputs, and barbiturate anesthesia modifies
their processing.
PMID- 10196449
TI - Reduced synaptophysin immunoreactivity in the dentate gyrus of prepulse
inhibition-impaired isolation-reared rats.
AB - Isolation rearing of rat pups from weaning produces neurochemical and behavioural
changes that may have relevance to the neurodevelopmental basis of
neuropsychiatric disorders such as schizophrenia. Although limited, studies have
begun to probe for neuroanatomical changes produced by isolation rearing. In the
present study, rat pups were reared in isolation, i.e., housed one per cage, from
weaning. After 8 weeks of isolation, 'isolates' were compared to their socially
reared controls (housed three per cage) in two behavioural paradigms: locomotor
activity in a novel open field and prepulse inhibition (PPI) of the acoustic
startle response. Subsequently, all rats were sacrificed and their brains
removed. The hippocampus was sectioned and analysed immunohistochemically using
an antibody to the synapse-specific protein synaptophysin, to gain an estimate of
the synaptic content of selected hippocampal subfields. Isolates demonstrated
locomotor hyperactivity and deficits in PPI relative to socially reared controls.
Analysis of synaptophysin immunoreactivity suggested that isolates had
significantly reduced synaptic content in the hippocampal dentate gyrus molecular
layer, with smaller, non-significant reductions in the CA1 and CA3 regions. This
pattern of change may be consistent with reduced neuronal input to the dentate
gyrus via the entorhinal cortex, suggesting developmental changes in hippocampal
cortical circuitry. These preliminary studies extend the characterisation of
isolation rearing as a model for the investigation of neurodevelopmental diseases
such as schizophrenia.
PMID- 10196450
TI - Axonal cytoskeleton changes in experimental optic neuritis.
AB - Axonal loss and degeneration in multiple sclerosis (MS) and experimental allergic
encephalomyelitis (EAE) have been suggested by brain imaging, pathological and
axonal transport studies. Further elucidation of the processes and mechanisms of
axonal degeneration in demyelinating diseases is therefore of potential
importance in order to alleviate the permanent disabilities of MS patients.
However, detailed studies in this area are impeded by the small number of
reliable models in which the onset and location of demyelination can be well
controlled. In this study, microinjection of polyclonal rabbit anti
galactocerebroside (anti-Gal C) antibody and guinea pig complement was used to
induce local demyelination in the rat optic nerve. We found that treatment with
appropriate volumes of the antibody and complement could induce local
demyelination with minimal pressure- or trauma-induced damage. Local changes in
neurofilaments (NFs) and microtubules (MTs) were examined with both
immunohistochemistry (IHC) and electron microscopy (EM). On day 1 after
microinjection, we observed moderate NF and MT disassembly in the local
demyelinated area, although in most cases, no apparent inflammatory cell
infiltration was seen. The NF and MT changes became more apparent on days 3, 5, 7
after microinjection, along with gradually increased inflammatory cell
infiltration. These results suggested that acute demyelination itself may induce
local cytoskeleton changes in the demyelinated axons, and that the ensuing local
inflammation may further enhance the axonal damage. When the lesions were stained
with specific antibodies for T lymphocytes, macrophages, and astrocytes, we found
that most of the cells were macrophages, suggesting that macrophages may play a
greater role in inflammation-related axonal degeneration and axonal loss. These
results were confirmed and further characterized on the ultrastructural level.
PMID- 10196451
TI - Myelinated afferent fiber types that become spontaneously active and
mechanosensitive following nerve transection in the rat.
AB - It is difficult to know which afferent types preferentially develop ectopic
firing characteristics following nerve injury because axotomy disconnects the
sensory receptor ending from the remainder of the afferent neuron. We compared
the prevalence of ectopic firing originating in nerve-end neuromas of nerves
serving muscle and skin in the rat. Spontaneous firing was much more prevalent in
the injured medial gastrocnemius nerve, a hindlimb muscle nerve, than in the
saphenous and sural nerves which primarily innervate hindlimb skin. Ectopic
mechanosensitivity, on the other hand, was more prominent in neuromas of the
cutaneous nerves. In neuromas of the facial nerve, a cranial nerve which serves
striated muscles of the face, there was no spontaneous discharge and very little
ectopic mechanosensitivity. We conclude that the development of spontaneous
ectopic discharge and ectopic mechanosensitivity depends on the type of
myelinated afferent fiber involved.
PMID- 10196452
TI - Differential vulnerability of dopamine receptors in the mouse brain treated with
MPTP.
AB - We investigated the chronological changes of dopamine D1 and D2 receptors and
dopamine uptake sites in the striatum and substantia nigra of mouse brain treated
with 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP) by quantitative
autoradiography using [3H]SCH23390, [3H]raclopride and [3H]mazindol,
respectively. The mice received i.p. injections of MPTP (10 mg/kg) four times at
intervals of 60 min, the brains were analyzed at 6 h and 1, 3, 7 and 21 days
after the last the injection. Dopamine D2 receptor binding activity was
significantly decreased in the substantia nigra from 7 to 21 days after MPTP
administration, whereas such binding activity was significantly increased in the
medial part of the striatum at 21 days. There was no alteration of dopamine D1
receptor binding activity in either the striatum or the substantia nigra for the
21 days. The number of dopamine uptake sites gradually decreased in the striatum
and the substantia nigra, starting at 6 h after MPTP administration, and the
lowest levels of binding activity were observed at 3 and 7 days in the striatum
(18% of the control values in the medial part and 30% in the lateral part) and at
1 day in the substantia nigra (20% of the control values). These results indicate
that severe functional damage to the dopamine uptake sites occurs in the striatum
and the substantia nigra, starting at an early stage after MPTP treatment. Our
findings also demonstrate the compensatory up-regulation in dopamine D2
receptors, but not dopamine D1 receptors, in the striatum after MPTP treatment.
Furthermore, our results support the existence of dopamine D2 receptors, but not
dopamine D1 receptors, on the nigral neurons. The present findings suggest that
there are differential vulnerabilities to MPTP toxicity in the nigrostriatal
dopaminergic receptor systems of mouse brain.
PMID- 10196453
TI - Lipopolysaccharide-induced changes in monoamines in specific areas of the brain:
blockade by interleukin-1 receptor antagonist.
AB - The purpose of this study was to examine the specificity in the effects of
lipopolysaccharide (LPS) on monoamine concentrations in different areas of the
brain and the involvement of interleukin-1 (IL-1) in the LPS-induced effects.
Adult male rats were injected i.p. with saline, 10 micrograms/kg body weight of
LPS, or treated with 250 micrograms of IL-1 receptor antagonist (IL-1ra) 5 min
before and 2 h after LPS. Several brain areas including the hippocampus (HI),
caudate putamen (CP), the hypothalamic paraventricular nucleus (PVN), arcuate
nucleus (AN), median eminence (ME) and the medial preoptic area (MPA) were
microdissected and analyzed for neurotransmitter concentrations by HPLC-EC. LPS
treatment produced marked increases in the concentrations of norepinephrine (NE),
dopamine (DA), serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5
HIAA) in the PVN. In the AN, it increased DA concentrations and was without any
effect on the MPA, ME, CP and HI. Treatment with IL-1ra in combination with LPS
completely blocked the LPS-induced effects. It is concluded that LPS produces
highly specific changes in monamine metabolism in the hypothalamus and that these
effects are mediated at least in part by IL-1beta.
PMID- 10196454
TI - Effects of changes in glucose concentration on synaptic plasticity in hippocampal
slices.
AB - The effects of a low or high concentration of glucose in the perfusion medium on
synaptic activity and plasticity were studied in hippocampal slices from rats.
Low-glucose medium depressed the field excitatory post-synaptic potentials
(fEPSP) significantly, whereas high-glucose medium had little effect on the
fEPSP. Tetanization of the afferent fibres elicited significant potentiation
(LTP) of synaptic activity irrespective of the glucose concentration in the
medium. This may indicate that LTP induction does not depend on optimal neural
transmission. Paired-pulse facilitation (PPF) experiments showed that the medium
glucose concentration did not significantly influence potentiation of the second
response.
PMID- 10196455
TI - Increased catecholamine levels in specific brain regions of a rat model of
depression: normalization by chronic antidepressant treatment.
AB - Alterations in catecholamine levels and neurotransmission have been shown in
depressive disorders. However, the exact sites of alterations and the relation
between these alterations to the etiology of the disease and the effectiveness of
antidepressant therapy are poorly understood. In this study, catecholamine levels
and metabolism were measured in specific brain regions of a genetic rat model of
depression [Flinders Sensitive Line (FSL) rats], and compared to normal Sprague
Dawley rats. Norepinephrine levels were found to be two to threefold higher in
the nucleus accumbens, prefrontal cortex, hippocampus and median raphe nucleus of
FSL rats as compared with control Sprague-Dawley rats. Dopamine levels were
sixfold higher in the nucleus accumbens and twofold higher in the striatum,
hippocampus and hypothalamus of FSL rats as compared with control Sprague-Dawley
rats. After chronic treatment with the antidepressant desipramine, the immobility
score in a swim test, as a measure of a behavioral deficit, as well as
catecholamine levels of the FSL rats became normalized, but these parameters in
the control rats did not change. The results indicate that the behavioral
deficits expressed in the FSL model for depression correlate with increased
catecholamine levels in specific brain sites, and further suggest the FSL rats as
a model for elucidation of the molecular mechanism of clinically used
antidepressant drugs.
PMID- 10196456
TI - Stress reduces morphine's antinociceptive potency: dependence upon spinal
cholecystokinin processes.
AB - The antinociceptive potency of opioids is altered by stress. We have shown that
repetitive exposure of rats to noxious heat produced stress-induced analgesia as
detected by the tail-flick test, but decreased the potency of the opioid beta
endorphin in the periaqueductal gray region of the midbrain (PAG). In this study,
we examined the effects of this same stressor on the antinociceptive actions of
the alkaloid narcotic, morphine, following either i.p. or intracerebral
administration. Regardless of the route of administration, a significant
reduction in the narcotic's ability to produce antinociception during stress was
observed. The stress-induced reduction in morphine's potency was reversed by the
intrathecal administration of the cholecystokinin (CCK) receptor antagonist L
365,260 (0.1 ng per rat), suggesting that spinal CCK-dependent 'anti-analgesic'
processes are involved. Since stress influences the potency of narcotics, it may
be an important physiological component to be considered in the clinical
management of pain. Moreover, CCK receptor antagonists may improve the
reliability of narcotic therapy.
PMID- 10196457
TI - Regulation of cyclic AMP level by progesterone in ovariectomized rat neocortex.
AB - Exposure of neocortical slices to progesterone, without prior treatment with
estrogen, augmented forskolin-induced cyclic AMP within 15 min. 30 nM
progesterone produced approximately 1/2 the maximal effect but as little as 10 nM
progesterone produced a detectable increase in cyclic AMP. When forskolin was
replaced by dideoxyforskolin, an analog that does not directly stimulate adenylyl
cyclase but shares many of its other actions, progesterone did not augment cyclic
AMP. Progesterone also failed to affect increased cyclic AMP that followed
exposure to norepinephrine or isoproterenol. The effect of progesterone upon
cyclic AMP was also evident when tetrodotoxin was added to block voltage
dependent sodium channels, suggesting that intercellular communication that is
dependent upon action potentials was not necessary. The effect of progesterone
was at least partially blocked by antagonists of GABAA receptor action,
suggesting the involvement of GABAA or GABAA-like receptors. The effect of
progesterone was also not homogeneous over the neo cortex. While forskolin
stimulated cyclic AMP was augmented by progesterone in the parietal and occipital
regions, it was suppressed in the frontal region. These results are envisioned as
a progesterone action upon a small and perhaps compartmentalized component of the
cellular cyclic AMP system, an effect that is made detectable in our whole-tissue
assay by the well known ability of forskolin to potentiate many hormonal effects
upon cyclic AMP.
PMID- 10196458
TI - Identification of neuronal input to the arcuate nucleus (ARH) activated during
lactation: implications in the activation of neuropeptide Y neurons.
AB - Activation of the neuropeptide Y (NPY) neuronal system in the arcuate nucleus of
the hypothalamus (ARH) during lactation in the rat is likely due to the neural
impulses arising from the suckling stimulus. However, the afferent neuronal input
to the ARH that is activated during lactation and is responsible for activation
of NPY neurons is currently unknown. Previously, using cFos as a marker for
neuronal activation, we identified several brain areas in the lactating animals
that were activated by the suckling stimulus. Thus, the objective of the present
study was to determine if these activated areas observed in the lactating animals
project directly into the ARH. The retrograde tracer, fluorogold (FG), was
injected into the ARH on day 4 postpartum. Chronically suckled rats were then
deprived of their eight-pup litters on day 9 postpartum, and 48 h later, the pups
were returned to the females to reinitiate the suckling stimulus for 90 min to
induce cFos expression. The animals were then perfused and the brains were
subjected to double-label immunohistochemistry to visualize both FG- and cFos
positive cells. Substantial FG/cFos double-labeled cells were found in forebrain
regions, including the medial preoptic area, periventricular preoptic area, bed
nucleus of the stria terminalis, and the medial amygdala, and in brainstem
regions including the lateral parabrachial nucleus, peripeduncular area and
ventrolateral medulla. The results of the present study demonstrate that specific
areas in the brain are activated during lactation and send direct projections to
the ARH. Thus, these areas are potentially important candidates for mediating the
activation of the NPY neuronal system in the ARH during lactation.
PMID- 10196459
TI - Influence of stimulation of the olivocerebellar pathway by harmaline on spatial
learning in the rat.
AB - Administration of harmaline to the rat, which activates synchronously and
rhythmically the olivary neurons and the olivocerebellar pathway, elicits visuo
motor, spatial learning and spatial memory deficiencies which are dose-dependent.
Since activation and lesion of the olivocerebellar pathway have similar effects,
it is concluded that normal functioning of this pathway is required for spatial
learning achievement.
PMID- 10196460
TI - Apoptotic cascade of neurons in the subcortical sensory relay nuclei following
the neonatal infraorbital nerve transection.
AB - A terminal transferase-mediated dUTP nick end labeling (TUNEL) method was
utilized for detection of neuronal death in the subcortical relay nuclei of the
trigeminosensory system following the infraorbital nerve transection in newborn
rats. At 18-24 h after injury, numerous TUNEL-positive profiles were found within
the ventroposteromedial thalamic nucleus (VPM) contralateral to the injury,
whereas the VPM on the ipsilateral side and of the age-matched normal control
contained only a few profiles per section. Electron microscopy revealed that the
TUNEL-positive profiles were apoptotic neurons. The ventral part of the
ipsilateral brainstem sensory trigeminal nuclear complex (the nucleus
principalis, and the subnuclei oralis and interpolaris) exhibited statistically
significant 65-70% increase in number of apoptotic neurons compared to the
contralateral side. Taken together with our previous study [T. Sugimoto, C. Xiao,
H. Ichikawa, Neonatal primary neuronal death induced by capsaicin and axotomy
involves an apoptotic mechanism, Brain Res. 807 (1998) 147-154], the present
results demonstrated a cascade of apoptosis in the primary, secondary and
tertiary order sensory neurons along the neuroaxis.
PMID- 10196461
TI - Mapping of secondary somatosensory cortex activation induced by vibrational
stimulation: an fMRI study.
AB - Sensory functional MRI was performed in seven normal volunteers at 1. 5 T using a
vibratory stimulus applied to the pad of the first finger of the left hand. The
data was normalized to a standard atlas, and individual and group statistical
parametric maps were computed. Robust bilateral activation was demonstrated in
the secondary somatosensory cortex (SII), indicating a bilateral representation
of SII in humans. Greater maxima and activation volumes were achieved in
contralateral SII as compared to SI. Sensory fMRI can provide a sensitive assay
for probing the nature and function of SII in vivo.
PMID- 10196462
TI - Development of inflammatory hypersensitivity and augmentation of sodium channels
in rat dorsal root ganglia.
AB - The development of thermal allodynia in relationship to sodium channel
augmentation in dorsal root ganglia (DRGs) was studied in albino rats. Paw
withdrawal latencies were measured hourly following complete Freund's adjuvant
(CFA) injections. Sodium channels were demonstrated with immunocytochemistry.
Sustained minimum latencies were attained between 10 and 12 h post-injection.
Sodium channel labeling began to increase at 23 h post-injection and reached
maximum levels by 24 h. Thermal hypersensitivity is thus established 12 h before
sodium channel augmentation can be demonstrated.
PMID- 10196463
TI - Impaired phosphorylation of cyclic AMP response element binding protein in the
hippocampus of dementia of the Alzheimer type.
AB - Cyclic AMP (cAMP) is disrupted in the brain in dementia of the Alzheimer type
(DAT). We investigated whether the cAMP reduction is accompanied by an alteration
in the cAMP response element binding protein (CREB) downstream in DAT and control
hippocampi. Immunoreactivity of pCREB was significantly decreased in DAT, while
total CREB level was unchanged. These findings indicate that impaired cAMP
signaling may contribute to the pathophysiology of the disease.
PMID- 10196464
TI - Regulation of CCK mRNA expression in the rat brain by stress and treatment with
sertraline, a selective serotonin re-uptake inhibitor.
AB - In this paper, we have investigated the regulation of CCK mRNA expression in the
brain after restraint stress with and without long-term treatment with the
selective serotonin reuptake inhibitor sertraline. Stress alone increases CCK
mRNA levels in the hippocampus, whereas no changes were found in the cerebral
cortex, amygdaloid complex and thalamus. CCK mRNA expression decreases in the
hippocampus, increases in the thalamus and was not modified in the cerebral
cortex and amygdaloid complex after sertraline alone. CCK mRNA content was
unchanged in all investigated areas after stress plus sertraline compared to
control rats.
PMID- 10196465
TI - Injury induces neuropsin mRNA in the central nervous system.
AB - We have shown that neuropsin is expressed in the neurons of the limbic system in
the adult mouse. After the central nervous system was injured by incision or
intraperitoneal kainate injection, neuropsin mRNA was induced in the peri
lesioned region. The cells in which neuropsin mRNA was induced were localized
mainly in axon fiber pathways and closely associated to proteolipid protein (PLP)
mRNA expressing oligodendrocytes.
PMID- 10196466
TI - Estrogen protects against 3-methylindole-induced olfactory loss.
AB - Olfactory dysfunction is among the first signs of Alzheimer's disease (AD). Since
estrogen therapy may mitigate the cognitive symptoms of AD, we determined whether
17beta-estradiol (E2) alters the olfactory discrimination performance of female
rats exposed to the olfactotoxicant 3-methylindole (3-MI). Twelve ovariectomized
rats received daily injections of E2 (1 mg/kg i.p.) in corn oil and 10 received
daily injections of corn oil alone. Sensory testing occurred on a near-daily
basis throughout a 10-week test period, midway in which a single injection of 3
MI was administered (300 mg/kg i.p.). On each pre- and post-3-MI test day, the
rats were required to perform a series of successively more difficult odor
discrimination tasks until one was reached where <80% performance was attained.
The tasks were between the odor of a 10-4 v/v concentration of ethyl acetate (EA)
and the odor of each of six different concentrations of butanol added to the EA
(10-4, 10-4.5, 10-5.0, 10-5.5, 10-6.0, 10-6.5 v/v). Following 3-MI treatment, the
performance of the E2-treated rats was found to be superior to that of the oil
treated rats and to return more quickly to the pre-3 MI baseline, suggesting that
high doses of E2 mitigate 3-MI-induced smell loss in rats. Additional work is
needed to determine the physiologic basis of this phenomenon.
PMID- 10196467
TI - Plant chromosomal HMGI/Y proteins and histone H1 exhibit a protein domain of
common origin.
AB - The chromosomal high-mobility-group (HMG) proteins of the HMGI/Y family interact
with A/T-rich stretches in duplex DNA, and are considered assistant factors in
transcriptional regulation. A cDNA encoding an HMGI/Y protein of 190 amino acid
residues was isolated from maize and characterized. Like other plant HMGI/Y
proteins, the maize HMGI/Y protein contains four copies of the AT-hook DNA
binding motif and an amino-terminal 'histone H1-like region' with a similarity to
the globular domain of H1. The maize hmgi/y gene that was isolated from a genomic
DNA library contains a single intron that is localized in the region of sequence
similarity to histone H1. Interestingly, the genes encoding plant H1 contain an
intron at exactly the same relative position, indicating an evolutionary
relationship of the plant genes encoding HMGI/Y and H1 proteins.
PMID- 10196468
TI - Characterization, cloning, and evolutionary history of the chloroplast and
cytosolic class I aldolases of the red alga Galdieria sulphuraria.
AB - Two fructose-1,6-bisphosphate aldolases from the acido- and thermophilic red alga
Galdieria sulphuraria were purified to apparent homogeneity and N-terminally
microsequenced. Both aldolases had similar biochemical properties such as Km
(FBP) (5.6-5.8 microM) and molecular masses of the native enzymes (165kDa) as
determined by size exclusion chromatography. The subunit size of the purified
aldolases, as determined by SDS-PAGE, was 42kDa for both aldolases. The
isoenzymes were not inhibited by EDTA or affected by cysteine or potassium ions,
implying that they belong to the class I group of aldolases, while other red
algae are known to have one class I and one class II aldolase inhibited by EDTA.
cDNA clones of the cytosolic and plastidic aldolases were isolated and sequenced.
The gene for the cytosolic isoenzyme contained a 303bp untranslated leader
sequence, while the gene for the plastidic isoenzyme exhibited a transit sequence
of 56 amino-acid residues. Both isoenzymes showed about 48% homology in the
deduced amino-acid sequences. A gene tree relates both aldolases to the basis of
early eukaryotic class I aldolases. The phylogenetic relationship to other
aldolases, particularly to cyanobacterial class II aldolases, is discussed.
PMID- 10196469
TI - Characterisation of XlCdc1, a Xenopus homologue of the small (PolD2) subunit of
DNA polymerase delta; identification of ten conserved regions I-X based on
protein sequence comparisons across ten eukaryotic species.
AB - DNA polymerase delta (Pol delta), which plays keys roles in DNA replication,
repair and recombination in eukaryotic cells, comprises at least two essential
subunits - a large catalytic subunit (PolD1) possessing both DNA polymerase and
3'-5' exonuclease activities, and a smaller subunit (PolD2) whose function is not
yet clear. Here we describe the cloning and sequencing of a Xenopus cDNA encoding
a homologue of the PolD2 subunit. This protein (designated XlCdc1) is 69%
identical to the human PolD2 protein and 34% identical to fission yeast Cdc1.
Alignment of PolD2 protein sequences across ten eukaryotic species identifies 36
invariant amino-acid positions. These 36 residues are located within ten
conserved regions (designated I-X) likely to have key functional roles.
Consistent with this, the mutations in six previously identified yeast mutant
PolD2 proteins map within conserved regions III, VI, VII and VIII. Several of the
invariant amino acids are also conserved across the archaeal DNA polymerase II
DP1 protein family.
PMID- 10196470
TI - Characterization of katD, a kinesin-like protein gene specifically expressed in
floral tissues of Arabidopsis thaliana.
AB - Kinesin and kinesin-like proteins (KLPs) are microtubule-based motor proteins
that play important roles in organelle transport. Based on the homology to these
proteins, a katD cDNA has now been isolated from a library prepared from flowers
of Arabidopsis thaliana ecotype Columbia. Sequence analysis of the katD cDNA
revealed an open reading frame of 2691bp [corrected], encoding a protein of 987
amino acids. Comparison of the nucleotide sequences of katD genomic and cDNA
clones revealed the presence of 18 introns, 17 of which conform to the GU-AG
rule. The central region of the KatD polypeptide exhibits substantial amino acid
sequence homology to the motor domain of kinesin heavy chains, although the motor
domain of KatD appears to be phylogenetically distant from those of other KLPs in
plants. The amino-terminal region of KatD shares marked sequence similarity with
the calponin homology domain, whereas the approximately 240-residue carboxyl
terminal region shows no significant homology to other known proteins. The
predicted secondary structure of KatD revealed the lack of an alpha-helical
coiled coil structure typical of kinesin heavy chains, suggesting that KatD may
function as a monomeric motor. A recombinant truncated KatD protein containing
the putative motor domain was shown both to bind to mammalian microtubules in a
manner dependent on a non-hydrolyzable ATP analog, and to possess microtubule
dependent ATPase activity. Immunoblot and Northern blot analyses showed that both
KatD protein and mRNA are expressed specifically in floral tissues. These results
suggest that the structurally distinct KatD protein functions as a floral tissue
specific motor protein.
PMID- 10196471
TI - Isolation and characterization of a cDNA clone from Arabidopsis thaliana with
partial sequence similarity to integrins.
AB - An Arabidopsis thaliana cDNA, called At14a, was isolated by immunoscreening an
expression library with an anti-integrin antibody. The At14a cDNA is 1459
nucleotides and has an open reading frame encoding a protein of 385 amino acids
and a predicted molecular weight of 43kDa. At14a has a small domain that has
sequence similarities to integrins from fungi, insects and humans. Transcripts of
At14a are found in all Arabidopsis tissues examined, and when expressed as an
epitope tagged fusion protein in transgenic plants, At14a localizes partly to the
plasma membrane.
PMID- 10196472
TI - Persistent expression of foreign genes in cultured hepatocytes: expression
vectors.
AB - We have optimized a liposome-based transfection method that mediated highly
efficient stable expression of foreign genes in hepatocytes. Moreover, we have
observed that the metallothionein 1 promoter in the bovine papilloma virus-based
expression vector drove the highest expression of foreign genes in hepatocytes as
compared with the cytomegalovirus and the human polypeptide chain elongation
factor 1alpha (EF-1alpha) promoters in the pcDNA 3-based expression vector. The
cytomegalovirus promoter failed to yield significant expression in these cells.
Furthermore, expression of foreign genes persisted up to at least 15 passages
when expression was under the control of either the EF-1alpha or the
metallothionein 1 promoter. Thus, these two promoters led to comparable stability
of foreign genes in hepatocytes, with the metallothionein 1 promoter yielding a
higher level of expression of foreign genes in these cells.
PMID- 10196473
TI - Allelic recombination and linkage disequilibrium within Msp-1 of Plasmodium
falciparum, the malignant human malaria parasite.
AB - The C-terminal, cysteine-rich 19kDa domain of merozoite surface protein-1 (MSP-1)
of Plasmodium falciparum is a target of the host's humoral immunity and thus a
malaria vaccine candidate. Although variation in the 19kDa domain is limited
among parasite isolates, tertiary structure-dependent intramolecular associations
between the 19kDa domain and other parts of MSP-1 are suggested to be involved in
immune evasion by allowing competitive binding of protective and non-protective
antibodies directed to their epitopes, which are conformationally in close
proximity but separated at the primary structure. Since allelic recombination can
account for the major variability of the Msp-1 gene, we examined whether linkage
disequilibrium occurs between polymorphic loci in the 5'- and the 3'-region, the
latter encoding the 19kDa domain. From 184 Thai field isolates, we selected 69
isolates with a single allelic type in six variable blocks of Msp-1 as determined
by PCR-based allelic typing. All the isolates showed no evidence of recombination
in blocks 6 to 16, whereas recombination was apparent in blocks 2 to 6.
Sequencing of the 3'-region revealed two potential recombination sites in block
17. Strong linkage disequilibrium was seen between polymorphic loci in the 5'-
and 3'-regions. The strength of this disequilibrium did not correlate with
distance between loci. We discuss the possible role of epistatic selection on
particular association types (haplotypes) of Msp-1.
PMID- 10196474
TI - Alternate Pax7 paired box transcripts which include a trinucleotide or a
hexanucleotide are generated by use of alternate 3' intronic splice sites which
are not utilized in the ancestral homologue.
AB - In the mouse, Pax7 plays an important role in development of the skeletal muscles
of the limbs, elements of the nervous system and cranio-facial structures. It is
expressed in the brain and skeletal muscles of the limbs in the mature mouse.
Recently, we have identified alternate transcripts that differ by inclusion or
exclusion of a trinucleotide and/or a hexanucleotide in the paired domain
encoding region. Sequencing of the paired box in genomic DNA from SJL/J and
BALB/c mice reveals that the trinucleotide and hexanucleotide are generated by
selection of alternate splice sites at the 3' terminus of each of the two paired
box introns, respectively. The proximal 3' splice site of the first intron, which
includes the trinucleotide in the mature transcript, is preferentially selected
in skeletal muscle and brain. By contrast, the proximal 3' splice site of the
second intron, which results in inclusion of the hexanucleotide in the mature
transcript, is preferentially selected only in skeletal muscle. The distal
alternate 3' splice site, which results in exclusion of the hexanucleotide in the
mature transcript, is preferentially selected in the brain. These findings raise
the possibility that there may be tissue-specific factors that influence the
specificity of the spliceosomal machinary. Reference to the structure of the
proposed primordial form of Pax7 suggests that the ability to utilize the
alternate splice sites that generate inclusion of the trinucleotide and the
hexanucleotide in the mature transcripts may have occurred in recent evolutionary
times.
PMID- 10196475
TI - The ClpB protein from Campylobacter jejuni: molecular characterization of the
encoding gene and antigenicity of the recombinant protein.
AB - The ClpB heat-shock protein is necessary for the survival of Escherichia coli
cells upon sudden increase of temperature. Using a PCR-based genomic walking
method, the nucleotide sequence of a clpB homolog from Campylobacter jejuni was
determined. The clpB gene encodes a protein of 857 amino acid (aa) residues, with
a predicted molecular mass of 95.3kDa. Alignment of the deduced aa sequence with
other known bacterial ClpB proteins revealed overall identity from 47% (E. coli)
to 61% (Helicobacter pylori). Within the clpB promoter region, as indicated by
primer extension analysis, we identified a sequence identical to the E. coli
sigma70 consensus promoter. Northern blot analysis confirmed that clpB is heat
inducible in C. jejuni. The ClpB protein, fused to a 6xHis tag, was synthesized
in E. coli and purified by metal-affinity and size exclusion chromatography. In
ELISA studies, IgA levels reactive to recombinant ClpB were significantly higher
in sera of patients with prior C. jejuni infections than in sera obtained from
healthy control persons.
PMID- 10196476
TI - Genomic organization of the human fibroblast growth factor receptor 2 (FGFR2)
gene and comparative analysis of the human FGFR gene family.
AB - The human fibroblast growth factor receptor (FGFR) genes play important roles in
normal vertebrate development. Mutations in the human FGFR2 gene have been
associated with many craniosynostotic syndromes and malformations, including
Crouzon, Pfeiffer, Apert, Jackson-Weiss, Beare-Stevenson cutis gyrata, and Antley
Bixler syndromes, and Kleeblaatschadel (cloverleaf skull) deformity. The
mutations identified to date are concentrated in the previously characterized
region of FGFR2 that codes for the extracellular IgIII domain of the receptor
protein. The search for mutations in other regions of the gene, however, has been
hindered by lack of knowledge of the genomic structure. Using a combination of
genomic library screening, long-range PCR, and genomic walking, we have
characterized the genomic structure of nearly the entire human FGFR2 gene,
including a delineation of the organization and size of all introns and exons and
determination of the DNA sequences at the intron/exon boundaries. Comparative
analysis of the human FGFR gene family reveals that the genomic organization of
the FGFRs is relatively conserved. Moreover, alignment of the amino acid
sequences shows that the four corresponding proteins share 46% identity overall,
with up to 70% identity between individual pairs of FGFR proteins. However, the
FGFR2 gene contains an additional exon not found in other members of the family,
and it also has much larger intronic sequences throughout the gene. Remarkable
similarities in genomic organization, intron/exon boundaries, and intron sizes
are found between the human and mouse FGFR2 genes. Knowledge gained from this
study of the human FGFR2 gene structure may prove useful in future screening
studies designed to find additional mutations associated with craniosynostotic
syndromes, and in understanding the molecular and cell biology of this receptor
family.
PMID- 10196477
TI - Isolation and characterization of the murine zinc finger coding gene, ZT2:
expression in normal and transformed myogenic cells.
AB - In the context of a project aimed at the identification of zinc finger proteins
involved in skeletal muscle histogenesis and differentiation, we isolated a
murine gene, named ZT2. The 2.44kb partial cDNA clone corresponds to the 3'
region of the gene, and contains a 0.54kb open reading frame encoding four C2H2
like zinc finger domains, organized in tandem. This cDNA hybridizes with multiple
transcripts (2, 4.5 and 7kb), whose expression levels vary in different tissues
and at different developmental stages in the same tissue. At least in skeletal
muscle we observed differences in the polyadenylation state of the transcripts at
different stages of development. Moreover, ZT2 expression is correlated with cell
proliferation and transformation. Sequence analysis and genetic mapping indicate
that ZT2 is the homologue of ZNF125, one of the linked zinc finger encoding genes
localized on human Chr 11q23. In humans, a high frequency of tumor-associated
translocations is found in this chromosome region. As expected, ZT2 maps to the
corresponding region on chromosome 9 in the mouse.
PMID- 10196478
TI - Molecular cloning and characterization of two sets of alpha-theta genes in the
rat alpha-like globin gene cluster.
AB - The highly heterogeneous rat hemoglobin system was investigated at the gene
level. Two regions of the alpha-like globin gene cluster from a Wistar rat were
isolated. Four lambda Dash recombinant clones carrying rat alpha-like globin
genes were localized on two distinct gene regions. A region of approximately 16kb
was found to contain the 5'-IIalpha1-psi theta 1-3' loci, and another of
approximately 24kb the 5'-IIalpha2-psi theta2-psiI alpha3-3' loci. Both IIalpha1
and IIalpha2 are considered to be active, coding the IIalpha-globin chain. The nt
sequences of IIalpha1 and IIalpha2 are identical except for six nt in the non
coding region. The psiI alpha3 locus is a truncated pseudogene. The putative
promoter region of an alpha-like globin gene is joined directly to the third
exon, homologous to that of Ialpha-globin cDNA. psi theta1 and psi theta2 are
also pseudogenes, as evidenced by several deletions located in the protein-coding
regions of these loci. The psi theta1 and psi theta2 loci exhibit extensive
homology, but the restriction maps of these genes and their flanking regions
differ considerably. Genomic Southern blot analyses of the total liver DNA from
six rats showed the existence of three theta-globin-related genes, including psi
theta1 and psi theta2. These results indicate that the two gene regions
investigated are not allelic variants, but may be generated by block duplication.
This is the first report of the existence of rodent theta-globin genes.
PMID- 10196479
TI - Intron splice sites of Papilio glaucus PglRh3 corroborate insect opsin phylogeny.
AB - Full-length cDNA clones encoding the PglRh3 opsin from the tiger swallowtail
butterfly Papilio glaucus were isolated from cDNA synthesized from adult head
tissue total RNA. This cDNA consists of 1679 nucleotides and contains a single
open reading frame predicted to be 379 amino acids in length. PCR amplification
of genomic DNA with primers spanning the coding region yielded a single 2760bp
fragment which was sequenced. The PglRh3 gene has nine exons and eight introns,
four of which are in unique locations relative to the positions of introns in
other known insect opsin sequences. Phylogenetic analyses of amino acid and
nucleotide sequence data places PglRh3 within a clade of insect visual pigments
thought to be sensitive to long wavelengths of light. The genomic structure of
PglRh3 is the first characterized from a member of this opsin clade. Three PglRh3
intron positions are shared with Drosophila Rh1, and one of these is also shared
with Drosophila Rh2. By contrast, none of the known intron locations in a clade
of anciently diverged ultraviolet- and blue-sensitive visual pigments are shared
by P. glaucus PglRh3, Drosophila Rh1 or Rh2. The placement of introns within
opsin genes therefore independently supports the clustering of a putatively long
wavelength-sensitive clade with a clade of blue-green-sensitive visual pigments.
PMID- 10196480
TI - An antisilencer element is involved in the transcriptional regulation of the
human vimentin gene.
AB - Vimentin is an intermediate filament protein normally expressed in cells of
mesenchymal origin. The promoter of the human vimentin gene was previously
reported to contain two positive-acting regions, separated by a negative region
(Rittling, S.R., Baserga, R., 1987. Functional analysis and growth factor
regulation of the human vimentin promoter. Mol. Cell. Biol. 7, 3908-3915). Here,
detailed studies reveal two additional regulatory elements, a new positive
transcriptional element located between -717 and -757, and a new repressor
element at -780 to -821. In transient transfections, the positive-acting element
is able to completely override the effect of different silencer elements when
fused to a heterologous promoter. However, this element does not enhance gene
activity when the silencer element is absent and thus cannot be viewed as a true
enhancer. Since it appears to overcome the effect of a silencer element, we refer
to it as an antisilencer element. Gel mobility shift assays, UV-cross-linking
experiments, and Southwestern blots reveal that a 105-kDa protein specifically
binds to this region.
PMID- 10196481
TI - Cloning and characterization of the gene encoding mouse osteoclast
differentiation factor.
AB - Osteoclast differentiation factor (ODF), a ligand for osteoclastogenesis
inhibitory factor (OCIF)/ osteoprotegerin (OPG), is a member of the membrane
associated tumor necrosis factor (TNF) family and induces osteoclast-like cell
formation in vitro. In the present study, mouse ODF genomic clones were isolated
and sequenced to determine their gene structure. The mouse ODF gene is a single
copy gene consisting of five exons and spans approximately 40kb of the mouse
genome. The first exon encodes the intracellular and transmembrane domains. The
extracellular region of ODF containing the TNF homologous domain is encoded by
exons 1 through 5. The translation-termination codon and six polyadenylation
signal residues are present in exon 5. A major transcription-initiation site is
present 143 nucleotides upstream of the initiation-ATG codon. This genomic
organization is similar to that of other members of the TNF family, especially
the CD40 ligand.
PMID- 10196482
TI - Outcomes management: trendy phrase or mandate for survival?
PMID- 10196483
TI - APACHE II and ISS scores as predictors of nosocomial infections in trauma
patients.
AB - BACKGROUND: Nosocomial infections affect more than 2 million patients annually in
the United States at a cost of $4.5 billion. The aim of this study is to identify
the role of the APACHE II score and the Injury Severity Scale (ISS) as
independent predictors of nosocomial infections in trauma patients admitted to
the intensive care unit (ICU). METHODS: A retrospective chart review of 113
trauma patients admitted to the ICU was conducted by an infectious disease
physician. Demographic data and incidence of nosocomial infections were recorded.
Multivariate logistic regression analysis was used to determine variables that
are predictive of the occurrence of nosocomial infections. RESULTS: Presence or
absence of intubation, ICU length of stay, APACHE II score, and ISS were related
to the presence of infections; however, only the ICU length of stay was an
independent predictor of a nosocomial infection, with an odds ratio of 1.81. By
linear regression, 17% of the variance in the ICU duration of stay was a result
of the APACHE II score in patients with a score >/=5. CONCLUSION: APACHE II score
and ISS score were not good predictors of the incidence of nosocomial infections
in trauma patients admitted to the ICU, but the APACHE II score has a modest
correlation with the duration of stay in the ICU. A stratified cohort study could
identify the subset of patients for which the APACHE II score predicts a
prolonged stay in the ICU, thus an increased risk of infection.
PMID- 10196484
TI - Improving the appropriateness of vancomycin use by sequential interventions.
AB - BACKGROUND: Vancomycin usage is directly associated with the incidence of
vancomycin-resistant enterococci. Optimal methods to reduce inappropriate use
have not been delineated. We determined the appropriateness of vancomycin
prescribing at our hospital on the basis of national guidelines and assessed the
effect of sequential administrative and educational interventions. METHODS: In
this prospective 3-phase study conducted in a Veterans Affairs Medical Center, we
monitored vancomycin prescribing at baseline and in 2 follow-up periods.
Administrative interventions included discussions with service chiefs and
revising routine perioperative antibiotic prophylaxis orders. Educational
interventions included in-services about vancomycin-resistant enterococci and
appropriate vancomycin prescribing. In each monitoring period, 50 consecutive new
vancomycin orders that could be evaluated were classified for appropriateness and
categorized by indication. RESULTS: At baseline, 70% of vancomycin use was
inappropriate. Surgical services accounted for 84% of orders. Interventions
targeted services with high or frequently inappropriate vancomycin use. After
administrative interventions, inappropriate vancomycin use dropped to 40% of
orders (P =.003). Improvements were noted in targeted services. Educational
interventions further decreased inappropriate vancomycin use, but the effect
appeared transient. CONCLUSIONS: The simple, nonrestrictive administrative
interventions used resulted in a statistically significant (30%) reduction in
inappropriate vancomycin prescribing. However, educational interventions provided
only transient benefit on institutional prescribing patterns.
PMID- 10196485
TI - Reducing the rate of nosocomially transmitted respiratory syncytial virus.
AB - BACKGROUND: A large number (17) of nosocomial respiratory syncytial virus cases
led to the development of control measures to prevent transmission of respiratory
syncytial virus (RSV) within the Johns Hopkins Hospital's Children's Center.
METHODS: The control plan is based on a 2-stage process. In stage 1, the staff
are notified that RSV is in the community, and information is distributed through
a communication tree. Stage 2 requires that nasopharyngeal aspirates be obtained
from all children <3 years of age who have respiratory symptoms. The aspirates
are tested directly for RSV antigen and cultured for RSV. The children are placed
on pediatric droplet precautions pending those results. RESULTS: The proportion
of nosocomial RSV cases dropped from 16.5% before the use of RSV control measures
to 7.2% after the initiation of the control program. A case of RSV identified in
the hospital was 2.6 times more likely to be nosocomially acquired before the
intervention compared with after the intervention. Approximately 14 cases of RSV
are prevented each year, which results in a savings of 56 hospital-days and more
than $84,000 in direct hospital-related charges alone. CONCLUSIONS: The
nosocomial spread of RSV can be reduced by a specific and feasible control plan
that includes early identification and rapid isolation of potential RSV cases.
PMID- 10196487
TI - Guideline for Prevention of Surgical Site Infection, 1999. Centers for Disease
Control and Prevention (CDC) Hospital Infection Control Practices Advisory
Committee.
AB - EXECUTIVE SUMMARY The "Guideline for Prevention of Surgical Site Infection, 1999"
presents the Centers for Disease Control and Prevention (CDC)'s recommendations
for the prevention of surgical site infections (SSIs), formerly called surgical
wound infections. This two-part guideline updates and replaces previous
guidelines.1,2 Part I, "Surgical Site Infection: An Overview," describes the
epidemiology, definitions, microbiology, pathogenesis, and surveillance of SSIs.
Included is a detailed discussion of the pre-, intra-, and postoperative issues
relevant to SSI genesis. Part II, "Recommendations for Prevention of Surgical
Site Infection," represents the consensus of the Hospital Infection Control
Practices Advisory Committee (HICPAC) regarding strategies for the prevention of
SSIs.3 Whenever possible, the recommendations in Part II are based on data from
well-designed scientific studies. However, there are a limited number of studies
that clearly validate risk factors and prevention measures for SSI. By necessity,
available studies have often been conducted in narrowly defined patient
populations or for specific kinds of operations, making generalization of their
findings to all specialties and types of operations potentially problematic. This
is especially true regarding the implementation of SSI prevention measures.
Finally, some of the infection control practices routinely used by surgical teams
cannot be rigorously studied for ethical or logistical reasons (e.g., wearing vs
not wearing gloves). Thus, some of the recommendations in Part II are based on a
strong theoretical rationale and suggestive evidence in the absence of
confirmatory scientific knowledge.It has been estimated that approximately 75% of
all operations in the United States will be performed in "ambulatory," "same
day," or "outpatient" operating rooms by the turn of the century.4 In
recommending various SSI prevention methods, this document makes no distinction
between surgical care delivered in such settings and that provided in
conventional inpatient operating rooms. This document is primarily intended for
use by surgeons, operating room nurses, postoperative inpatient and clinic
nurses, infection control professionals, anesthesiologists, healthcare
epidemiologists, and other personnel directly responsible for the prevention of
nosocomial infections. This document does not: Specifically address issues unique
to burns, trauma, transplant procedures, or transmission of bloodborne pathogens
from healthcare worker to patient, nor does it specifically address details of
SSI prevention in pediatric surgical practice. It has been recently shown in a
multicenter study of pediatric surgical patients that characteristics related to
the operations are more important than those related to the physiologic status of
the patients.5 In general, all SSI prevention measures effective in adult
surgical care are indicated in pediatric surgical care. Specifically address
procedures performed outside of the operating room (e.g., endoscopic procedures),
nor does it provide guidance for infection prevention for invasive procedures
such as cardiac catheterization or interventional radiology. Nonetheless, it is
likely that many SSI prevention strategies also could be applied or adapted to
reduce infectious complications associated with these procedures. Specifically
recommend SSI prevention methods unique to minimally invasive operations (i.e.,
laparoscopic surgery). Available SSI surveillance data indicate that laparoscopic
operations generally have a lower or comparable SSI risk when contrasted to open
operations.6-11 SSI prevention measures applicable in open operations (e.g., open
cholecystectomy) are indicated for their laparoscopic counterparts (e.g.,
laparoscopic cholecystectomy). Recommend specific antiseptic agents for patient
preoperative skin preparations or for healthcare worker hand/forearm antisepsis.
Hospitals should choose from products recommended for these activitie
PMID- 10196489
TI - Role of surveillance in emerging health systems: measurement is essential but not
sufficient.
PMID- 10196490
TI - APIC guidelines committee: using science to guide practice. Association for
Professionals in Infection Control and Epidemiology.
PMID- 10196491
TI - Job analysis 1996: Infection control professional. Certification Board in
Infection Control and Epidemiology, Inc, 1996 Job Analysis Committee.
AB - The Certification Board in Infection Control and Epidemiology, Inc, directed its
Test and Administrative Subcommittees to compose a Job Analysis Committee in
1995. This 16-member Job Analysis Committee, in collaboration with Applied
Measurement Professionals, Inc, conducted a job analysis survey of infection
control professionals in the United States and Canada during 1996. The
reassessment of the previous Certification Board in Infection Control and
Epidemiology, Inc, task analysis, formation of a job-analysis survey tool, the
actual job-analysis process, and its results are described in this article. The
previous and newly revised test specification outlines are compared. The Revised
Certification Examination for Infection Control offered beginning in 1997 will
reflect the efforts of this endeavor.
PMID- 10196492
TI - Outcomes of a postdischarge surveillance system for surgical site infections at a
Midwestern regional referral center hospital.
AB - BACKGROUND: Postdischarge surveillance has been reported in the literature as one
method for detecting surgical site infections (SSIs) that more traditional
methods of surveillance (review of readmission data, monitoring of microbiology,
radiology, pharmacy antibiotic usage reports, and medical record review) fail to
include. METHODS: This article describes a postdischarge surveillance program
that used surgeon questionnaires and was implemented at a 225-bed Midwestern
regional referral center hospital. Evaluation of the postdischarge program was
accomplished by review of infection control program data for calendar years 1995
through 1997. RESULTS: Implementation of the postdischarge program resulted in an
almost fourfold increase (in both 1995 and 1996) in SSI rates over the reported
SSI rates if only traditional surveillance methods had been used. A majority of
surgeons (79% in 1995 and 83% in 1996) had individual response rates of 80% or
greater. In addition, implementation of the postdischarge program required only
3.5 to 4 additional hours per month. CONCLUSIONS: Results suggest that the
postdischarge surveillance program identified SSIs missed by traditional
surveillance methods, resulted in higher reported rates of SSI, was moderately to
well accepted by surgeons, and was implemented with a minimum of organizational
resources.
PMID- 10196493
TI - Effective cost-reduction strategies in the management of regulated medical waste.
PMID- 10196494
TI - RNA virus of hepatitis G (GB virus) prevalence in health care personnel.
PMID- 10196495
TI - Additional cost savings of an effective employee influenza program on prevention
of nosocomial influenza.
PMID- 10196496
TI - Evaluating the protective value of hospital gowns...
PMID- 10196498
TI - Potential applications of intracardiac echocardiography in the assessment of the
aortic valve from the right ventricular outflow tract.
AB - Intracardiac echocardiography (ICE) is a developing technology and a promising
method for visualizing intracardiac structures. However, its applications are
currently limited to guidance during mitral valvuloplasty, catheter ablation, or
electrophysiologic examination. The goal of this study was to observe the aortic
valve, measure the annular diameter of the valve by ICE through a right-sided
approach, and compare the results by ICE with those by transthoracic
echocardiography (TTE) or transesophageal echocardiography (TEE). We studied 18
patients (9 men, 9 women, aged 19 to 72 years) with various heart diseases,
including 15 patients with mitral or aortic valvular disease. An imaging catheter
was advanced through a long sheath into the outflow tract of the right ventricle.
We obtained good longitudinal views of the aortic valve in all patients. Two of
the 18 patients had poor image quality by TTE. The annular diameter by ICE
correlated more closely with TEE than with TTE. In conclusion, right-sided ICE is
a safe, simple, and useful procedure for observing the aortic valve during
cardiac catheterization without additional discomfort in the patients. Right
sided ICE is superior to TTE in observing the aortic valve and measuring the
annular diameter of the valve. The annular diameter can be measured by ICE as
precisely as by TEE.
PMID- 10196499
TI - Intraoperative transesophageal echocardiography in minimally invasive cardiac
valve surgery.
AB - The minimally invasive procedure is a new surgical technique that uses a small
sternal incision. Because of limited surgical exposure, removal of intracavitary
air and visual assessment of cardiac function are not possible. We studied the
utility of intraoperative transesophageal echocardiography (IOE) before and after
cardiopulmonary bypass in 112 patients (mean age 53.1 +/- 15.2 years, 74 males)
who underwent minimally invasive valvular surgery. Surgical procedures included
52 isolated mitral valve procedures (49 repairs, 3 prostheses), 58 isolated
aortic valve procedures (16 repairs, 26 prostheses, 16 homografts), and 2
combined aortic and mitral valve repairs. Prepump IOE was useful to confirm valve
dysfunction and assist determination of arterial cannulation site. Postpump IOE
identified intracardiac air in all patients, which was defined as extensive in 58
(52%) cases. Postoperatively, new left ventricular dysfunction was noted in 22
(20%) patients, more often in the group with extensive air by IOE (17 [30%] of 58
patients) compared with those without extensive air (5 [10%] of 54 patients, P
=.01). Second pump runs were required in 7 (6%) of 112 patients: 3 cases of
residual aortic regurgitation, 1 case of residual mitral regurgitation, and 3
cases with new ventricular dysfunction. No deaths occurred. We conclude that IOE
is essential in minimally invasive valvular surgery because it detects problems
that require immediate remedy. IOE allows real-time assessment of ventricular
filling, ventricular and valvular function, and intracardiac air.
PMID- 10196500
TI - Comparison of intraoperative transesophageal echocardiographic examinations with
the operative findings: prospective review of 1918 cases.
AB - The purpose of this study was to prospectively compare the intraoperative
transesophageal echocardiographic (IOTEE) findings with the operative findings in
1918 consecutive cardiac cases. Forty-eight discordant findings were found
between the IOTEE and operative findings. Of the 48 discordant findings, most
were related to valve pathology. Structural abnormalities that were missed by
IOTEE included those of the aortic valve, 12 cases (25%), mitral valve, 13 cases
(27%), and pulmonic and tricuspid valves, 5 cases (10%). Functional discrepancies
occurred in 8% of cases. Overall, incidence of discrepant findings between IOTEE
and operative findings was low (2.5%). This resulted in an alteration of the
planned surgical procedure in a small number of cases (0.3%).
PMID- 10196501
TI - Assessment of transmural coronary blood flow with intraoperative transesophageal
color Doppler echocardiography during coronary revascularization.
AB - Intraoperative color Doppler transesophageal echocardiography with a 4- to 7-MHz
transducer was performed on 28 consecutive patients who underwent coronary artery
bypass grafting to image and evaluate the transmural coronary blood flow before
and after cardiopulmonary bypass. The transmural coronary flow was visualized in
26 (92.8%) of 28 patients in the inferior wall and in 13 (46.4%) of 28 patients
in the lateral wall. The peak diastolic flow velocity of the transmural coronary
artery in the inferior and lateral wall was significantly increased after
coronary revascularization in patients with a successful bypass graft to the
right coronary artery (from 34.0 +/- 19.7 to 64.9 +/- 30.9 cm/s, P <.001, n = 10)
and to the left circumflex coronary artery (from 35.1 +/- 18.6 to 62.1 +/- 21.1
cm/s, P <.001, n = 10). No significant changes were observed in patients with no
bypass graft to the right or left circumflex coronary artery. Coronary blood flow
can be mapped and the velocity measured with Doppler transesophageal
echocardiography with a high-frequency (4- to 7-MHz) transducer. Assessment of
the transmural coronary flow may provide valuable information and aid in decision
making during surgical revascularization.
PMID- 10196502
TI - Improved high-frequency transthoracic flow velocity measurement in the left
anterior descending coronary artery after intravenous peripheral injection of
levovist.
AB - New ultrasonic technology allows noninvasive measurement of the flow in the
distal left anterior descending coronary artery. The goal of this study was to
validate transthoracic determination of coronary flow velocity with the
intracoronary Doppler flow wire technique. In 20 patients with normal coronary
arteries, 2 intracoronary and 2 comparative transthoracic Doppler measurements
(TTDMs) of the average peak velocity (APV) and the mean systolic and diastolic
velocities were performed. The diastolic/systolic ratio was calculated. Blood
flow velocity was determined in the distal left anterior descending coronary
artery with a Doppler guide wire. Color Doppler and subsequent pulsed wave
Doppler readings in an optimal left lateral position were available within 1 hour
after completion of the invasive examinations. TTDM were performed during
continuous administration of 2.0 g of contrast agent. A modified apical view was
obtained from the fourth or fifth intercostal space, and a high-frequency
transducer was used (7 MHz for 2-dimensional and 6 MHz for color Doppler imaging;
3.5 MHz for pulsed wave Doppler readings). The Doppler flow signal quality was
graded from I to III (I = no flow mapping obtainable, II = poor quality, III =
Doppler signals with a well-defined outline). In 13 (65%) patients, 26 TTDMs
revealed signal quality of grade III. APV was calculated to be within normal
limits (APVecho = 19.96 +/- 7.62 cm/s vs APVinvasive = 20.77 +/- 7.87 cm/s).
APVecho correlated well with APVinvasive (r = 0.85, y = 0.82x + 2.85, P <.001).
The mean difference between APVecho and APVinvasive (Bias) was -0.81 +/- 4.23
cm/s. No correlation was found between invasive and noninvasive measurements of
diastolic/systolic velocity ratios (P >.05). High-frequency TTDM provides
reliable data on APV in the majority of patients. It has the potential to be
introduced as a relevant screening test for follow-up of patients after
interventional treatment.
PMID- 10196503
TI - Assessment of flow mismatch with pharmacologic stress test on myocardial contrast
echocardiography in a model of critical stenosis: adenosine triphosphate and
dipyridamole.
AB - Although adenosine triphosphate (ATP) is a favorable vasodilator because of its
short-acting duration, the agent's effectiveness in facilitating the diagnosis of
myocardial ischemia with myocardial contrast echocardiography (MCE) is not fully
understood. The goal of this study was to examine the efficacy of intravenous ATP
administration (0.15 to 0.30 mg/kg/min for 5 minutes) in diagnosing the flow
mismatch with MCE. To achieve this, a critical stenosis was produced in the left
circumflex artery in 10 anesthetized dogs. The peak intensity ratio of risk area
to control area was reduced by ATP from 0.51 +/- 0.19 to 0.31 +/- 0.12 (P <.05).
Systolic wall thickening of the risk area did not change significantly (32.8% +/-
9.8% to 27.5% +/- 12.8%). These changes did not differ from those obtained after
dipyridamole. We conclude that MCE with intravenous ATP administration is as
useful as the dipyridamole method for diagnosing critical coronary stenosis.
PMID- 10196504
TI - Real-time visualization of myocardial perfusion and wall thickening in human
beings with intravenous ultrasonographic contrast and accelerated intermittent
harmonic imaging.
AB - Previous work has demonstrated that at higher peak negative pressures,
microbubbles are destroyed by diagnostic ultrasonography. At lower pressures
(lower mechanical index), less destruction occurs but enhanced contrast persists.
In animals, this lower mechanical index has resulted in enhanced contrast after
administration of intravenous microbubbles with intermittent imaging at faster
frame rates. We tested whether this accelerated intermittent imaging technique
could produce myocardial contrast and detect myocardial perfusion abnormalities
in 25 patients (10 with normal wall motion, 15 after myocardial infarction).
Three independent reviewers detected persistent myocardial contrast defects
within the infarct zone throughout the cardiac cycle in 9 of the 15 patients
after acute myocardial infarction; the presence of such defects was predictive of
a persistent regional wall motion abnormality at 4-week follow-up. Interobserver
agreement on regional contrast enhancement ranged from 88% to 90%. We conclude
that accelerated intermittent imaging permits real-time visualization of
myocardial blood flow and wall thickening.
PMID- 10196506
TI - Right lateral transthoracic approach mimicking standard transesophageal
echocardiographic views in a patient with giant left atrium.
AB - We describe the case of a patient with long-standing severe mitral periprosthetic
regurgitation and a giant left atrium. The patient was referred for surgery. On
the third postoperative day, after resuture of the dehiscence of the valve sewing
ring, the patient complained of dyspnea. Transthoracic ultrasound examination was
performed to eliminate pleural effusion. The severe right lateral displacement of
an aneurysmatic left atrial cavity contacting with the thoracic wall allowed us
to obtain excellent images of the posterior cardiac anatomy by a right lateral
thoracic view. The new transthoracic approach made it possible to safely assess
the atrial side of the mitral prosthesis, eliminating mitral regurgitation after
surgery without transesophageal echocardiographic examination.
PMID- 10196505
TI - Potential utility of left heart contrast agents in diagnosis of myocardial
rupture by 2-dimensional echocardiography.
AB - This case illustrates the use of intravenous injections of a contrast agent
during 2-dimensional echocardiography in a patient with myocardial rupture after
myocardial infarction. Intravenous injections of echocardiographic contrast
agents may have potential use in the identification of intrapericardial
hemorrhage after myocardial infarction caused by myocardial rupture or
development of ventricular pseudoaneurysm.
PMID- 10196507
TI - Cardiovascular applications of the Doppler technique: A long way from birth to
scientific acceptance.
AB - Analysis of the early developments of cardiac Doppler illustrates a gap,
frequently encountered in science, between initial concepts and final acceptance.
Acceptance may only emerge as a result of multidisciplinary collaboration and
fruitful dialogue between physicians, physiologists, physicists, and engineers.
By 1980, after a good deal of trial and error and a long period of incremental
improvement, the majority of the theoretic and scientific issues had been
defined. The explosive development of Doppler techniques can now intervene to
sweep aside the medical community's scepticism.
PMID- 10196508
TI - Search for Extrapancreatic Effects of New Oral Hypoglycemic Agent A-4166: 1. Oral
Glucose Tolerance Tests in Normal and Hereditary Insulin Resistant Rats.
AB - OBJECTIVE: To test the effect of new oral hypoglycemic compound A-4166 on insulin
secretion during oral glucose challenge in normal and hereditary non-obese,
hypertriglyceridemic, insulin resistant and hypertensive rats fed either a normal
or high fat diet. METHODS: The rats used were 15 weeks old males of Wistar
Charles River strain (controls) and Wistar-derived hereditary
hypertriglyceridemic (hHTg) rats of our own colony. They were fed either basal
(12 cal% of fat) or high fat diet (70 cal% fat). After 3 weeks of feeding the
above diets, the oral glucose tolerance tests (2 g/kg) were carried out in
unrestrained conscious rats kept in special metabolic cages after overnight
fasting and ten minutes after the administration of A-4166 (100 mg/kg) or placebo
by the stomach tube. Plasma glucose, triglycerides, free fatty acids and insulin
levels were measured by routine analytical methods. RESULTS: High fat diet
feeding resulted in an increase in fasting plasma insulin in both rat strains,
while fasting plasma glucose in high fat diet fed animals remained unchanged as
compared to those fed basal diet. No differences in the fasting FFA levels were
found. The glucose area under curve (AUC) did not differ between the two strains
used and high fat diet resulted in a higher glucose AUC in both strains. The
administration of A-4166 improved the glucose tolerance in all animals, namely in
those fed the basal diet. Insulin AUC showed very similar pattern in both rat
strains proving the stimulatory effect of A-4166 on insulin secretion during an
oral glucose challenge. High fat feeding resulted in an impairment of insulin
action, but the administration of A-4166 restored the antilipolysis in both
strains to the normal range. CONCLUSIONS: The previously reported hypoglycemic
action of A-4166 resulting from the increased insulin secretion was confirmed.
Moreover, some beneficial action of A-4166 on antilipolysis in vivo was
demonstrated.
PMID- 10196509
TI - Influence of Ethynodiol Diacetate on the Formation of A-Homo-3Oxa-5?-Pregnane
4,20-Dione in Female Rats.
AB - OBJECTIVE: To give more insight in the progesterone metabolism in rat after the
treatment with the progestin ethynodiol diacetate. METHODS: Urinary excretion of
the metabolites of subcutaneously administred (4-14C)-progesterone was studied in
female rats. After an acid hydrolysis and extraction of urine the metabolites
were analysed by thin layer chromatography and by gas chromatography-mass
spectrometry. RESULTS: The most of radioactivity was excreted during the first 24
h, and total of 8.36 % has been recovered within four days. The excreted
metabolites in urine were found as glucuronides and free steroids (80.72 %), and
19.28 % were determined as sulphates. Among detected metabolites, 5alpha-pregnane
3,20-dione, 3alpha-hydroxy-5alpha-pregnan-20-one and A-homo-3-oxa-5alpha-pregnane
4,20-dione were determined in the urinary extracts. The last one has not yet been
identified before in rat urine. CONCLUSIONS: Consecutive injections of progestin
ethynodiol diacetate (6 mg/kg b.w. daily) to adult female rats during 10 days
(short-term treatment), or during 70 days (long-term treatment), starting on the
21st day of life, caused significant differences in the amounts of excreted
3alpha-hydroxy-5alpha-pregnan-20-one and A-homo-3-oxa-5alpha-pregnane-4,20-dione.
Significant increase in the weights of pituitary, liver and kidneys were noted in
rats treated with ethynodiol diacetate. The short-term treatment caused an
increase, while after the long-term treatment a decrease of the ovarian weight
was observed.
PMID- 10196510
TI - Early Postnatal Glutamate Treatment Results in Altered Vascular Responsiveness to
Serotonin and Noradrenaline in Adult Rats.
AB - OBJECTIVES: To evaluate possible alterations of vascular responsiveness to
vasoactive hormones in the vessel preparations from adult rats treated neonatally
with high doses of glutamate. METHODS: The responses to noradrenaline and
serotonin in perfused hindlimb vascular bed and isolated renal artery were
measured in MSG-treated (2 and 4 mg/g BW) and control groups of adult rats at the
age of 10 weeks. Acetylcholine test was used to assess the endothelium-dependent
relaxation of the hindlimb vascular preparation. The vessel specimens from this
vascular bed were evaluated histologically. RESULTS: Vasoconstrictory responses
to noradrenaline and serotonin were significantly reduced in the hindlimb
vascular bed in MSG-treated rats. In the renal artery, a significant decrease of
the responses to noradrenaline was found without significant changes in the
responses to serotonin. The observed changes were more pronounced in groups
treated with a high dose of MSG. Comparison of relaxing responses to
acetylcholine in the hindlimb preparation did not show any statistically
significant differences in control and MSG treated groups. Histological
evaluation of this preparations did not reveal any endothelial damage or
morphological changes of vessel wall. CONCLUSIONS: The obtained results showed
reduced vascular responsiveness to vasoconstrictory agents in adult rats
neonatally treated with MSG suggesting that early postnatal administration of
glutamate may result in irreversible changes in cardiovascular function.
PMID- 10196511
TI - Radioimmunoassay for Aquaporin-2.
AB - OBJECTIVE: To develop radioimmunoassay for aquaporin-2 (AQP-2). METHODS: Anti-AQP
2 antiserum has been raised in New Zealand white rabbits immunized with a
conjugate of synthetic AQP-2 peptide (257-271) with bovine serum albumin.
Radioiodination of synthetic peptide (tyrosine-AQP2 (257-271) was performed by
chloramine T method, followed by purification of radioiodinated material on
Sephadex G-25 column. RESULTS: The obtained antibody did not crossreact with
vasopressin, pituitary hormones, hypothalamic hormones and neuropeptides. The
assay was performed with a double antibody system. The values are expressed as an
equivalent of synthetic AQP-2 peptide (257-271). The dilution curve of high AQP-2
urine in radioimmunoassay system was parallel to the standard curve. The recovery
percentage of AQP-2 added to urine was about 100 % in this assay system. Intra
assay and inter-assay variation was 4.5 % and 7.2 %, respectively. Mean urinary
excretion of AQP-2 was 1.16 ng equivalent of AQP-2 (257-271)/mg creatine and was
lower in patients with diabetes insipidus. CONCLUSION: These data suggest that
his assay system is a suitable to measure AQP-2 in urine.
PMID- 10196512
TI - Acrosomal Component of Rat Round Spermatids Recognized by a Novel Monoclonal
Antibody.
AB - OBJECTIVE: To characterize immunocytochemically the antigen recognized which
appears at specific stages of germ cell development and acrosomal biogenesis by
the novel monoclonal antibody (Mab 3C2). METHODS: The novel monoclonal antibody
(Mab 3C2) raised against testicular Sertoli and germ cells. RESULTS: The
immunoreactivity of this Mab in testicular sections from immature 20-day-old rats
was confined to the pachytene spermatocytes. In adult testis the Mab 3C2, besides
meiotic cells, recognized also acrosomal component of round spermatids. The
immune reaction was observed in Golgi and cap phases of acrosomal development
until the stage VIII of the cycle of the seminiferous epithelium. Immunostaining
was absent in acrosome of elongating and mature spermatids and indicated that
some modifications in acrosomal protein may exist in subsequent stages of
acrosomal development. CONCLUSIONS: Novel Mab 3C2 shares a common antigen in
pachytene spermatocytes and round spermatids. Therefore, it may be a marker of
meiotic and postmeiotic germ cells.
PMID- 10196513
TI - Repeated Maternal Deprivation Alters Behavioral Pattern and Attenuates Prolactin
Response to Mild Stressor in Adult Male Wistar Rats.
AB - OBJECTIVE: To evaluate the impact of repeated neonatal mother deprivation (RMD)
of male rats on the behavioral parameters and response of prolactin to mild
stress stimuli in the adulthood. METHODS: Afer birth, the pups of Wistar Porton
Olac rats were crossfostered and their number was adjusted to 8 per litter (4
males and 4 females). They were removed from the dam for 6 hours daily on
postnatal day 6, 7, 8 and for 12 hours daily on postnatal day 12, 13, 15, 16 and
placed to another cage lined with cotton wool at controlled temperature 37 oC.
Body weight was estimated repeatedly from postnatal day 9 to 97. At 14 weeks of
life the behavioral activity was measured in an open field on 2 occasions, 2 days
apart. One week later the rats were exposed to 15 min novelty stress or to 3 min
handling and decapitated 15 min after the initiation of both. Trunk blood was
collected and plasma prolactin (PRL) was measured by radioimmunoassay. RESULTS:
On postnatal day 15 the eye opening was found in 75 % of control pups and 73 % of
pups with RMD. In the rats after RMD the body weight gain was significantly
decreased from day 21 until the day 97. Vertical behavioral activity (rearing)
was enhanced in RMD rats when measured on the first occasion. Horizontal
behavioral activity did not significantly differ from the control group. Stress
of novel environment elicited the activation of PRL secretion in untreated
animals (19.3 1+4.6 ng/ml vs. 7.17+1.03 ng/ml, P<0.05), while no change was found
in the rats after RMD (8.15+2.0 ng/ml vs. 4.35+0.48 ng/ml). CONCLUSIONS: In the
rats exposed to neonatal mother deprivation the lower emotionality was found.
Significantly decreased body weight gain in these animals was probably due to the
nutritional deprivation during the postnatal separation from the mother. The
nonresponsiveness of lactotrophs to mild stressor in adult rats after RMD may
have a negative impact on defense mechanisms to immune challenges.
PMID- 10196514
TI - Pseudomeningitis caused by Acinetobacter baumannii.
PMID- 10196515
TI - Analyzing the auditory scene.
PMID- 10196516
TI - Has a new color area been discovered?
PMID- 10196517
TI - Of vulcan ears, human ears and 'earprints'.
PMID- 10196518
TI - Opening the third eye.
PMID- 10196519
TI - Intrathalamic connections: a new way to modulate cortical plasticity?
PMID- 10196520
TI - How do our brains analyze temporal structure in sound?
PMID- 10196521
TI - Molecular identification of the corticosterone-sensitive extraneuronal
catecholamine transporter.
PMID- 10196522
TI - Development of language-specific phoneme representations in the infant brain.
PMID- 10196523
TI - Genetic dissection of Alzheimer's disease and related dementias: amyloid and its
relationship to tau.
AB - Molecular genetic analysis is revealing the etiologies of Alzheimer's disease
(AD) and related dementias. Here we review genetic and molecular biological
evidence suggesting that the peptide A beta 42 is central to the etiology of AD.
Recent data also suggests that dysfunction in the cytoskeletal protein tau is on
the pathway that leads to neurodegeneration and dementia. Tau is produced either
indirectly, by A beta 42, or directly, in some forms of frontotemporal dementia
by mutations in tau itself. These data support are refine the amyloid cascade
hypothesis for AD and suggest that understanding the causes and consequences of
tau dysfunction is an important priority for dementia research.
PMID- 10196524
TI - An unusual cGMP pathway underlying depolarizing light response of the vertebrate
parietal-eye photoreceptor.
AB - All cellular signaling pathways currently known to elevate cGMP involve the
activation of a guanylyl cyclase to synthesize cGMP. Here we describe an
exception to this rule. In the vertebrate parietal eye, the photoreceptors
depolarize to light under dark-adapted conditions, unlike rods and cones but like
most invertebrate photoreceptors. We report that the signaling pathway for this
response involves a rise in intracellular cGMP resulting from an inhibition of
the phosphodiesterase that hydrolyzes cGMP. Furthermore, this phosphodiesterase
is driven by an active G protein in darkness. These results indicate an
antagonistic control of the phosphodiesterase by two G proteins, analogous to the
Gs/Gi control of adenylyl cyclase. Our findings demonstrate an unusual
phototransduction mechanism and at the same time indicate that signaling
involving cyclic nucleotides is more elaborate than previously known.
PMID- 10196525
TI - Glutamate-induced neuron death requires mitochondrial calcium uptake.
AB - We have investigated the role of mitochondrial calcium buffering in excitotoxic
cell death. Glutamate acts at NMDA receptors in cultured rat forebrain neurons to
increase the intracellular free calcium concentration. Although concurrent
inhibition of mitochondrial calcium uptake substantially enhanced this
cytoplasmic calcium increase, it significantly reduced glutamate-stimulated
neuronal cell death. Mitochondrial inhibition did not affect nitric oxide
production or MAP kinase phosphorylation, which have been proposed to mediate
excitotoxicity. These results indicate that very high levels of cytoplasmic
calcium are not necessarily toxic to forebrain neurons, and that potential-driven
uptake of calcium into mitochondria is required to trigger NMDA-receptor
stimulated neuronal death.
PMID- 10196526
TI - A null mutation in TGF-alpha leads to a reduction in midbrain dopaminergic
neurons in the substantia nigra.
AB - Transforming growth factor (TGF)-alpha is neurotrophic for midbrain dopaminergic
neurons in vitro. Here I investigated whether a null mutation in the TGF-alpha
gene affects the normal development or survival of dopaminergic neurons in either
the substantial nigra (SN) or the ventral tegmental area (VTA). The SN of TGF
alpha knockout mice contained 50% fewer dopaminergic neurons than the control SN,
but VTA neuron number was unchanged. In addition, the overall volume of the
dorsal striatum was reduced by 20%. Newborn mice showed a similar decrease in the
number of SN dopaminergic neurons, suggesting that TGF-alpha is unlikely to
regulate developmental neuron death. These studies indicate that TGF-alpha is
required for the normal proliferation or differentiation of a select population
of dopaminergic neurons within the SN.
PMID- 10196527
TI - Presynaptic long-term depression at a central glutamatergic synapse: a role for
CaMKII.
AB - CaMKII is a calcium-activated kinase that is abundant in neurons and has been
strongly implicated in memory and learning. Here we show that low-frequency
stimulation of glutamatergic afferents in hippocampal slices from juvenile
domestic chicks results in long-term depression of synaptic transmission. This
reduction does not require activation of NMDA or metabotropic glutamate receptors
and does not require a rise in postsynaptic calcium. However, buffering
presynaptic calcium prevents the reduction of the excitatory postsynaptic
potential or current that is induced by low-frequency stimulation. In addition,
application of the calmodulin antagonist calmidazolium, or the specific CaMKII
antagonist KN-93, completely blocks long-term depression. These findings
demonstrate a newly discovered form of long-term synaptic depression in the avian
hippocampus.
PMID- 10196528
TI - Mechanoelectrical transduction assisted by Brownian motion: a role for noise in
the auditory system.
AB - The organs of the vestibular, auditory and lateral line systems rely on a common
strategy for the stimulation of their primary receptors, the hair cells: stimuli
induce shear between hair cell epithelia and accessory structures to which hair
bundles, the hair cells' mechanosensitive organelles, are attached. The inner
hair cells of the cochlea, whose hair bundles are not attached to the overlying
tectorial membrane, are a notable exception. Because their hair bundles are not
restrained, they undergo significant Brownian motion, a characteristic
traditionally thought to blunt the sensitivity of hearing. Contrary to this view,
the work reported here indicates that Brownian motion of the hair bundle serves
to enhance the sensitivity of mechanoelectrical transduction.
PMID- 10196529
TI - A new intrathalamic pathway linking modality-related nuclei in the dorsal
thalamus.
AB - Transmission of sensory information through the dorsal thalamus involves two
types of modality-related nuclei, first order and higher order, between which
there are thought to be no intrathalamic interactions. We now show that within
the somatosensory thalamus, cells in one nucleus, the ventrobasal complex, can
influence activity in another nucleus, the medial division of the posterior
complex. Stimulation of ventrobasal complex cells evoked inhibitory postsynaptic
currents in cells of the medial division of the posterior complex. These currents
exhibited the reversal potential and pharmacology of a GABAA receptor-mediated
chloride conductance, indicating that they result from the activation of a
disynaptic pathway involving the GABAergic cells of the thalamic reticular
nucleus. These findings provide the first direct evidence for intrathalamic
interactions between dorsal thalamic nuclei.
PMID- 10196530
TI - Functional connectivity between simple cells and complex cells in cat striate
cortex.
AB - In the cat primary visual cortex, neurons are classified into the two main
categories of simple cells and complex cells based on their response properties.
According to the hierarchical model, complex receptive fields derive from
convergent inputs of simple cells with similar orientation preferences. This
model received strong support from anatomical studies showing that many complex
cells lie within the range of layer IV simple-cell axons but outside the range of
most thalamic axons. Physiological evidence for the model, however, has remained
elusive. Here we demonstrate that layer IV simple cells and layer II and III
complex cells show correlated firing consistent with monosynaptic connections. As
expected from the hierarchical model, all connections were in the direction from
the simple cell to the complex cell, most frequently between cells with similar
orientation preferences.
PMID- 10196531
TI - A neural correlate for vestibulo-ocular reflex suppression during voluntary eye
head gaze shifts.
AB - The vestibulo-ocular reflex (VOR) is classically associated with stabilizing the
visual world on the retina by producing an eye movement of equal and opposite
amplitude to the motion of the head. Here we have directly measured the efficacy
of VOR pathways during voluntary combined eye-head gaze shifts by recording from
individual vestibular neurons in monkeys whose heads were unrestrained. We found
that the head-velocity signal carried by VOR pathways is reduced during gaze
shifts in an amplitude-dependent manner, consistent with results from behavioral
studies in humans and monkeys. Our data support the hypothesis that the VOR is
not a hard-wired reflex, but rather a pathway that is modulated in a manner that
depends on the current gaze strategy.
PMID- 10196532
TI - Expectation of reward modulates cognitive signals in the basal ganglia.
AB - Action is controlled by both motivation and cognition. The basal ganglia may be
the site where these kinds of information meet. Using a memory-guided saccade
task with an asymmetric reward schedule, we show that visual and memory responses
of caudate neurons are modulated by expectation of reward so profoundly that a
neuron's preferred direction often changed with the change in the rewarded
direction. The subsequent saccade to the target was earlier and faster for the
rewarded direction. Our results indicate that the caudate contributes to the
determination of oculomotor outputs by connecting motivational values (for
example, expectation of reward) to visual information.
PMID- 10196533
TI - Relearning sound localization with new ears.
AB - Because the inner ear is not organized spatially, sound localization relies on
the neural processing of implicit acoustic cues. To determine a sound's position,
the brain must learn and calibrate these cues, using accurate spatial feedback
from other sensorimotor systems. Experimental evidence for such a system has been
demonstrated in barn owls, but not in humans. Here, we demonstrate the existence
of ongoing spatial calibration in the adult human auditory system. The spectral
elevation cues of human subjects were disrupted by modifying their outer ears
(pinnae) with molds. Although localization of sound elevation was dramatically
degraded immediately after the modification, accurate performance was steadily
reacquired. Interestingly, learning the new spectral cues did not interfere with
the neural representation of the original cues, as subjects could localize sounds
with both normal and modified pinnae.
PMID- 10196535
TI - Making the most of transgenic mice.
PMID- 10196534
TI - Analysis of temporal structure in sound by the human brain.
AB - For over a century, models of pitch perception have been based on the frequency
composition of the sound. Pitch phenomena can also be explained, however, in
terms of the time structure, or temporal regularity, of sounds. To locate the
mechanism for the detection of temporal regularity in humans, we used functional
imaging and a 'delay-and-add' noise, which activates all frequency regions
uniformly, like noise, but which nevertheless produces strong pitch perceptions
and tuneful melodies. This stimulus has temporal regularity that can be
systematically altered. We found that the activity of primary auditory cortex
increased with the regularity of the sound. Moreover, a melody composed of delay
and-add 'notes' produced a distinct pattern of activation in two areas of the
temporal lobe distinct from primary auditory cortex. These results suggest a
hierarchical analysis of time structure in the human brain.
PMID- 10196537
TI - Ion-binding sites in NMDA receptors: classical approaches provide the numbers.
PMID- 10196536
TI - Calcium tsunamis: do astrocytes transmit cell death messages via gap junctions
during ischemia?
PMID- 10196538
TI - Interneurons and the ghost of the sea.
PMID- 10196539
TI - Axon guidance mechanisms: semaphorins as simultaneous repellents and anti
repellents.
PMID- 10196540
TI - Bimanual coupling in amputees with phantom limbs.
PMID- 10196541
TI - Unraveling the central nervous system pathways underlying responses to leptin.
AB - Here we summarize recent progress in the biology of leptin, concentrating on its
central nervous system (CNS) actions. The product of the ob gene, leptin is a
circulating hormone produced by white adipose tissue that has potent effects on
feeding behavior, thermogenesis and neuroendocrine responses. Leptin regulates
energy homeostasis, as its absence in rodents and humans causes severe obesity.
We consider the physiological mechanisms underlying leptin action, along with
several novel hypothalamic neuropeptides that affect food intake and body weight.
The molecular causes of several other obesity syndromes are discussed to
illuminate how the CNS regulates body weight. We describe neural circuits that
are downstream of leptin receptors and propose a model linking populations of
leptin-responsive neurons with effector neurons underlying leptin's endocrine,
autonomic and behavioral effects.
PMID- 10196542
TI - Binding sites for permeant ions in the channel of NMDA receptors and their
effects on channel block.
AB - We report the presence of binding sites for permeant monovalent cations at the
internal and external entrances to the channel of NMDA receptors. We measured the
effects of changing internal cesium (Cs+) and external sodium (Na+)
concentrations on the channel-blocking kinetics of the adamantane derivatives IEM
1754 and IEM-1857. Binding of Na+, or of Cs+ after it permeates the channel, to
sites at the external channel entrance prevents blockers from entering the
channel. Binding of Na+ to a blocked channel prevents blocker unbinding. Cs+
binding to a site at the internal channel entrance prevents IEM-1754 from
occupying the deeper of its two sites of block. The results show the critical
effects of permeant ions on the kinetics, affinity and voltage-dependence of
channel blockers.
PMID- 10196543
TI - Formation of intermediate-conductance calcium-activated potassium channels by
interaction of Slack and Slo subunits.
AB - Large-conductance calcium-activated potassium channels (maxi-K channels) have an
essential role in the control of excitability and secretion. Only one gene Slo is
known to encode maxi-K channels, which are sensitive to both membrane potential
and intracellular calcium. We have isolated a potassium channel gene called Slack
that is abundantly expressed in the nervous system. Slack channels rectify
outwardly with a unitary conductance of about 25-65 pS and are inhibited by
intracellular calcium. However, when Slack is co-expressed with Slo, channels
with pharmacological properties and single-channel conductances that do not match
either Slack or Slo are formed. The Slack/Slo channels have intermediate
conductances of about 60-180 pS and are activated by cytoplasmic calcium. Our
findings indicate that some intermediate-conductance channels in the nervous
system may result from an interaction between Slack and Slo channel subunits.
PMID- 10196544
TI - GluR5 kainate receptor activation in interneurons increases tonic inhibition of
pyramidal cells.
AB - We studied the modulation of GABAergic inhibition by glutamate and kainate acting
on GluR5-containing kainate receptors in the CA1 hippocampal region. Glutamate,
kainate or ATPA, a selective agonist of GluR5-containing receptors, generates an
inward current in inhibitory interneurons and cause repetitive action potential
firing. This results in a massive increase of tonic GABAergic inhibition in the
somata and apical dendrites of pyramidal neurons. These effects are prevented by
the GluR5 antagonist LY 293558. Electrical stimulation of excitatory afferents
generates kainate receptor-mediated excitatory postsynaptic currents (EPSCs) and
action potentials in identified interneurons that project to the dendrites and
somata of pyramidal neurons. Therefore glutamate acting on kainate receptors
containing the GluR5 subunit may provide a protective mechanism against
hyperexcitability.
PMID- 10196545
TI - Synaptic activation of kainate receptors on hippocampal interneurons.
AB - Although kainate receptor activation has been known to evoke epileptiform
activity, little is known about the role of kainate receptors in synaptic
transmission. Here we report that kainate (KA) receptors are present on
interneurons and, when activated, cause a large increase in the frequency of
spontaneous inhibitory postsynaptic currents (IPSCs) driven by action potentials.
Stimulation of excitatory afferents generates a pharmacologically identifiable
synaptic current mediated by KA receptors in interneurons. This synaptic current
is similar to that mediated by AMPA receptors in its response to short stimulus
trains, current-voltage relations and coefficient of variation, but it is much
smaller in peak amplitude and much slower. KA application also considerably
depresses evoked IPSCs. This depression seems to be in large part an indirect
consequence of the repetitive firing evoked by the activation of the
interneuronal somatic/dendritic KA receptors.
PMID- 10196546
TI - Semaphorins A and E act as antagonists of neuropilin-1 and agonists of neuropilin
2 receptors.
AB - Neuropilin-1 (NP-1) has been identified as a necessary component of a semaphorin
D (SemD) receptor that repulses dorsal root ganglion (DRG) axons during
development. SemA and SemE are related to SemD and bind to NP-1, but do not
repulse DRG axons. By expressing NP-1 in retinal neurons and NP-2 in DRG neurons,
we demonstrate that neuropilins are sufficient to determine the functional
specificity of semaphorin responsiveness. SemA and SemE block SemD binding to NP
1 and abolish SemD repulsion in axons expressing NP-1. SemA and SemE seem to have
a newly discovered protein antagonist capacity at NP-1 receptors, whereas they
act as agonists at receptors containing NP-2.
PMID- 10196547
TI - Gap-junction-mediated propagation and amplification of cell injury.
AB - Gap junctions are conductive channels that connect the interiors of coupled
cells. We determined whether gap junctions propagate transcellular signals during
metabolic stress and whether such signaling exacerbates cell injury. Although
overexpression of the human proto-oncogene bcl2 in C6 glioma cells normally
increased their resistance to injury, the relative resistance of bcl2+ cells to
calcium overload, oxidative stress and metabolic inhibition was compromised when
they formed gap junctions with more vulnerable cells. The likelihood of death was
in direct proportion to the number and density of gap junctions with their less
resistant neighbors. Thus, dying glia killed neighboring cells that would
otherwise have escaped injury. This process of glial 'fratricide' may provide a
basis for the secondary propagation of brain injury in cerebral ischemia.
PMID- 10196548
TI - Coding of visual information by precisely correlated spikes in the lateral
geniculate nucleus.
AB - Correlated firing among neurons is widespread in the nervous system. Precisely
correlated spiking, occurring on a millisecond time scale, has recently been
observed among neurons in the lateral geniculate nucleus with overlapping
receptive fields. We have used an information-theoretic analysis to examine the
role of these correlations in visual coding. Considerably more information can be
extracted from two cells if temporal correlations between them are considered.
The percentage increase in information depends on the degree of correlation; the
average increase is approximately 20% for strongly correlated pairs. Thus,
precise temporal correlation could be used as an additional information channel
from thalamus to visual cortex.
PMID- 10196549
TI - Visual interactions in the path of apparent motion.
AB - When two stationary visual objects appear in alternating sequence, they evoke the
perception of a single object moving back and forth between them. This is known
as stroboscopic or apparent motion and forms the basis of perceived continuity
in, for example, motion pictures. When the spatiotemporal separation between the
inducing objects is optimal, the subjective appearance of apparent motion is
nearly indistinguishable from that of real motion. Here we report that the
detection and identification of a simple visual form in the path of apparent
motion is impaired by the illusory perception of an object moving through the
empty space between the locations at which the inducing objects are presented.
This observation may be a manifestation of perceptual completion or 'filling in'
during apparent motion perception. We propose that feedback from higher to lower
visual cortical areas activates an explicit neural representation of a moving
object, which can then disrupt the representation of visual stimuli in the path
of the movement.
PMID- 10196550
TI - Gating of auditory responses in the vocal control system of awake songbirds.
AB - Nucleus HVc of the avian song system is a forebrain structure critical in song
production, perception and learning. Here we show that most HVc neurons that
respond to auditory stimuli under anesthesia show no responses to the same
stimulus in the awake, unrestrained bird. This suppression of auditory responses
in awake birds does not occur in the forebrain field L complex, which is one of
the auditory input stages for HVc. Gating of auditory input at the junction
between the auditory and vocal control system may be essential for regulating
auditory feedback signals necessary for song learning and maintenance.
PMID- 10196551
TI - Long-term temporal integration in the anuran auditory system.
AB - Analysis of the temporal structure of acoustic signals is important for the
communication and survival of a variety of animals including humans. Recognition
and discrimination of particular temporal patterns in sounds may involve
integration of auditory information presented over hundreds of milliseconds or
seconds. Here we show neural evidence for long-term integration in the anuran
auditory system. The responses of one class of auditory neurons in the torus
semicircularis (auditory midbrain) of frogs reflect the integration of
information, gathered over approximately 45-150 ms, from a series of stimulus
pulses, not stimulus energy. This integration process is fundamental to the
selective responses of these neurons for particular call types.
PMID- 10196552
TI - Functional anatomy of saccadic adaptation in humans.
AB - Positron emission tomography (PET) was used to investigate the neurophysiological
substrate of human saccadic adaptation. Subjects made saccadic eye movements
toward a visual target that was displaced during the course of the initial
saccade, a time when visual perception is suppressed. In one condition,
displacement was random from trial to trial, precluding any systematic
modification of the initial saccade amplitude. In the second condition, the
direction and magnitude of displacement were consistent, causing adaptative
modification of the initial saccade amplitude. PET difference images reflecting
metabolic changes attributable to the process of saccadic adaptation showed
selective activation of the medioposterior cerebellar cortex. This localization
is consistent with neurophysiological findings in monkeys and brain-lesioned
humans.
PMID- 10196553
TI - Maintaining internal representations: the role of the human superior parietal
lobe.
AB - In sensorimotor integration, sensory input and motor output signals are combined
to provide an internal estimate of the state of both the world and one's own
body. Although a single perceptual and motor snapshot can provide information
about the current state, computational models show that the state can be
optimally estimated by a recursive process in which an internal estimate is
maintained and updated by the current sensory and motor signals. These models
predict that an internal state estimate is maintained or stored in the brain.
Here we report a patient with a lesion of the superior parietal lobe who shows
both sensory and motor deficits consistent with an inability to maintain such an
internal representation between updates. Our findings suggest that the superior
parietal lobe is critical for sensorimotor integration, by maintaining an
internal representation of the body's state.
PMID- 10196554
TI - Does neuroscience threaten human values?
PMID- 10196555
TI - Survival of expanded dopaminergic precursors is critical for clinical trials.
PMID- 10196556
TI - Synaptic depression: a key player in the cortical balancing act.
PMID- 10196557
TI - Gephyrin, a major player in GABAergic postsynaptic membrane assembly?
PMID- 10196558
TI - Toward a molecular biology of memory: the light's coming on!
PMID- 10196559
TI - Electrophysiology and behavior converge in human extrastriate cortex.
PMID- 10196560
TI - Inferring behavior from functional brain images.
PMID- 10196561
TI - A v-SNARE participates in synaptic vesicle formation mediated by the AP3 adaptor
complex.
AB - Reconstitution of synaptic vesicle formation in vitro has revealed a pathway of
synaptic vesicle biogenesis from endosomes that requires the heterotetrameric
adaptor complex AP3. Because synaptic vesicles have a distinct protein
composition, the AP3 complex should selectively recognize some or all of the
synaptic vesicle proteins. Here we show that one element of this recognition
process is the v-SNARE, VAMP-2, because tetanus toxin, which cleaves VAMP-2,
inhibited the formation of synaptic vesicles and their coating with AP3 in vitro.
Mutant tetanus toxin and botulinum toxins, which cleave t-SNAREs, did not inhibit
synaptic vesicle production. AP3-containing complexes isolated from coated
vesicles could be immunoprecipitated by a VAMP-2 antibody. These data imply that
AP3 recognizes a component of the fusion machinery, which may prevent the
production of inert synaptic vesicles.
PMID- 10196562
TI - The long internal loop of the alpha 3 subunit targets nAChRs to subdomains within
individual synapses on neurons in vivo.
AB - Different types of neurotransmitter receptors coexist within single neurons and
must be targeted to discrete synaptic regions for proper function. In chick
ciliary ganglion neurons, nicotinic acetylcholine receptors (nAChRs) containing
alpha 3 and alpha 5 subunits are concentrated in the postsynaptic membrane,
whereas alpha-bungarotoxin receptors composed of alpha 7 subunits are localized
perisynaptically and excluded from the synapse. Using retroviral vector-mediated
gene transfer in vivo, we show that the long cytoplasmic loop of alpha 3 targets
chimeric alpha 7 subunits to the synapse and reduces endogenous nAChR surface
levels, whereas the alpha 5 loop does neither. These results show that a
particular domain of one subunit targets specific receptor subtypes to the
interneuronal synapse in vivo. Moreover, our findings suggest a difference in the
mechanisms that govern assembly of interneuronal synapses as compared to the
neuromuscular junction in vertebrates.
PMID- 10196563
TI - Postsynaptic clustering of major GABAA receptor subtypes requires the gamma 2
subunit and gephyrin.
AB - Most fast inhibitory neurotransmission in the brain is mediated by GABAA
receptors, which are mainly postsynaptic and consist of diverse alpha and beta
subunits together with the gamma 2 subunit. Although the gamma 2 subunit is not
necessary for receptor assembly and translocation to the cell surface, we show
here that it is required for clustering of major postsynaptic GABAA receptor
subtypes. Loss of GABAA receptor clusters in mice deficient in the gamma 2
subunit, and in cultured cortical neurons from these mice, is paralleled by loss
of the synaptic clustering molecule gephyrin and synaptic GABAergic function.
Conversely, inhibiting gephyrin expression causes loss of GABAA receptor
clusters. The gamma 2 subunit and gephyrin are thus interdependent components of
the same synaptic complex that is critical for postsynaptic clustering of
abundant subtypes of GABAA receptors in vivo.
PMID- 10196564
TI - Afferent-specific innervation of two distinct AMPA receptor subtypes on single
hippocampal interneurons.
AB - Using the polyamine toxin philanthotoxin, which selectively blocks calcium
permeable AMPA receptors, we show that synaptic transmission onto single
hippocampal interneurons occurs by afferent-specific activation of philanthotoxin
sensitive and -insensitive AMPA receptors. Calcium-permeable AMPA receptors are
found exclusively at synapses from mossy fibers. In contrast, synaptic responses
evoked by stimulation of CA3 pyramidal neurons are mediated by calcium
impermeable AMPA receptors. Both pathways converge onto single interneurons and
can be discriminated with Group II mGluR agonists. Thus, single interneurons
target AMPA receptors of different subunit composition to specific postsynaptic
sites, providing a mechanism to increase the synapse-specific computational
properties of hippocampal interneurons.
PMID- 10196565
TI - Use-dependent AMPA receptor block in mice lacking GluR2 suggests postsynaptic
site for LTP expression.
AB - The mechanisms responsible for enhanced transmission during long-term
potentiation (LTP) at CA1 hippocampal synapses remain elusive. Several popular
models for LTP expression propose an increase in 'use' of existing synaptic
elements, such as increased probability of transmitter release or increased
opening of postsynaptic receptors. To test these models directly, we studied a
GluR2 knockout mouse in which AMPA receptor transmission is rendered sensitive to
a use-dependent block by polyamine compounds. This method can detect increases
during manipulations affecting transmitter release or AMPA receptor channel open
time and probability, but shows no such changes during LTP. Our results indicate
that the recruitment of new AMPA receptors and/or an increase in the conductance
of these receptors is responsible for the expression of CA1 LTP.
PMID- 10196566
TI - Frequency-dependent synaptic depression and the balance of excitation and
inhibition in the neocortex.
AB - The stability of cortical neuron activity in vivo suggests that the firing rates
of both excitatory and inhibitory neurons are dynamically adjusted. Using dual
recordings from excitatory pyramidal neurons and inhibitory fast-spiking neurons
in neocortical slices, we report that sustained activation by trains of several
hundred presynaptic spikes resulted in much stronger depression of synaptic
currents at excitatory synapses than at inhibitory ones. The steady-state
synaptic depression was frequency dependent and reflected presynaptic function.
These results suggest that inhibitory terminals of fast-spiking cells are better
equipped to support prolonged transmitter release at a high frequency compared
with excitatory ones. This difference in frequency-dependent depression could
produce a relative increase in the impact of inhibition during periods of high
global activity and promote the stability of cortical circuits.
PMID- 10196567
TI - Stimulation of cAMP response element (CRE)-mediated transcription during
contextual learning.
AB - Recent studies suggest that the CREB-CRE transcriptional pathway is pivotal in
the formation of some types of long-term memory. However, it has not been
demonstrated that stimuli that induce learning and memory activate CRE-mediated
gene expression. To address this issue, we used a mouse strain transgenic for a
CRE-lac Z reporter to examine the effects of hippocampus-dependent learning on
CRE-mediated gene expression in the brain. Training for contextual conditioning
or passive avoidance led to significant increases in CRE-dependent gene
expression in areas CA1 and CA3 of the hippocampus. Auditory cue fear
conditioning, which is amygdala dependent, was associated with increased CRE
mediated gene expression in the amygdala, but not the hippocampus. These data
demonstrate that learning in response to behavioral conditioning activates the
CRE transcriptional pathway in specific areas of brain.
PMID- 10196568
TI - The MAPK cascade is required for mammalian associative learning.
AB - Mitogen-activated protein kinase (MAPK) is an integral component of cellular
signaling during mitogenesis and differentiation of mitotic cells. Recently MAPK
activation in post-mitotic cells has been implicated in hippocampal long-term
potentiation (LTP), a potential cellular mechanism of learning and memory. Here
we investigate the involvement of MAPK in learning and memory in behaving
animals. MAPK activation increased in the rat hippocampus after an associative
learning task, contextual fear conditioning. Two other protein kinases known to
be activated during hippocampal LTP, protein kinase C and alpha
calcium/calmodulin protein kinase II, also were activated in the hippocampus
after learning. Inhibition of the specific upstream activator of MAPK, MAPK
kinase (MEK), blocked fear conditioning. Thus, classical conditioning in mammals
activates MAPK, which is necessary for consolidation of the resultant learning.
PMID- 10196569
TI - Alcohol preference and sensitivity are markedly reduced in mice lacking dopamine
D2 receptors.
AB - Although dopaminergic transmission has been strongly implicated in alcohol self
administration, the involvement of specific dopamine receptor subtypes has not
been well established. We studied the ethanol preference and sensitivity of D2
receptor-deficient mice to directly evaluate whether dopamine D2 receptors
contribute to alcohol (ethanol) consumption. We report a marked aversion to
ethanol in these mice, relative to the high preference and consumption exhibited
by wild-type littermates. Sensitivity to ethanol-induced locomotor impairment was
also reduced in these mutant mice, although they showed a normal locomotor
depressant response to the dopamine D1 antagonist SCH-23390. These data
demonstrate that dopamine signaling via D2 receptors is an essential component of
the molecular pathway determining ethanol self-administration and sensitivity.
PMID- 10196570
TI - Integration of surface information in primary visual cortex.
AB - Ample evidence suggests that primary visual cortex is involved in the perception
of form, and there is increasing evidence that it may also be important in the
perception of surfaces. Perceptual qualities of surfaces, such as brightness, are
based on extensive integration of information throughout the visual field. In
primary visual cortex, we found that the responses of neurons to surfaces were
also influenced by the intensity and organization of light in large portions of
the visual field. Interactions with surrounding stimuli typically extended 10 to
20 degrees beyond a cell's receptive field the same spatial scale as perceptual
interactions. Moreover, there were both facilitatory and inhibitory influences,
just as there are additive and substractive perceptual interactions.
Surprisingly, influences from outside the receptive field obtained with surface
stimuli did not reliably correlate with influences recorded with gratings. These
properties suggest that the underlying neuronal interactions may serve as the
fundamental building blocks of surface perception.
PMID- 10196571
TI - Simultaneous encoding of tactile information by three primate cortical areas.
AB - We used simultaneous multi-site neural ensemble recordings to investigate the
representation of tactile information in three areas of the primate somatosensory
cortex (areas 3b, SII and 2). Small neural ensembles (30-40 neurons) of broadly
tuned somatosensory neurons were able to identify correctly the location of a
single tactile stimulus on a single trial, almost simultaneously. Furthermore,
each of these cortical areas could use different combinations of encoding
strategies, such as mean firing rate (areas 3b and 2) or temporal patterns of
ensemble firing (area SII), to represent the location of a tactile stimulus.
Based on these results, we propose that ensembles of broadly tuned neurons,
located in three distinct areas of the primate somatosensory cortex, obtain
information about the location of a tactile stimulus almost concurrently.
PMID- 10196572
TI - The time course of cortical facilitation during cued shifts of spatial attention.
AB - Adaptive behavior requires the rapid switching of attention among potentially
relevant stimuli that appear in the environment. The present study used an
electrophysiological approach to continuously measure the time course of visual
pathway facilitation in human subjects as attention was shifted from one location
to another. Steady-state visual evoked potentials (SSVEPs) were recorded to
rapidly flickering lights at attended and unattended locations, and variations in
SSVEP amplitude over time were calculated after a cue to shift attention. The
build-up of cortical facilitation reflected in SSVEP amplitude was found to bear
a close temporal relationship with the emergence of accurate target
discriminations at the newly attended location.
PMID- 10196573
TI - Central cancellation of self-produced tickle sensation.
AB - A self-produced tactile stimulus is perceived as less ticklish than the same
stimulus generated externally. We used fMRI to examine neural responses when
subjects experienced a tactile stimulus that was either self-produced or
externally produced. More activity was found in somatosensory cortex when the
stimulus was externally produced. In the cerebellum, less activity was associated
with a movement that generated a tactile stimulus than with a movement that did
not. This difference suggests that the cerebellum is involved in predicting the
specific sensory consequences of movements, providing the signal that is used to
cancel the sensory response to self-generated stimulation.
PMID- 10196574
TI - Citation data: the wrong impact?
PMID- 10196575
TI - He's got rhythm: single neurons signal timing on a scale of seconds.
PMID- 10196576
TI - Young neurons for old brains?
PMID- 10196577
TI - Perception of heading is a brain in the neck.
PMID- 10196578
TI - Two sodium channels contribute to the TTX-R sodium current in primary sensory
neurons.
PMID- 10196579
TI - Light detection in a 'blind' mammal.
PMID- 10196580
TI - Latency difference, not spatial extrapolation.
PMID- 10196581
TI - Phenylethanolamines inhibit NMDA receptors by enhancing proton inhibition.
AB - The phenylethanolamines, ifenprodil and CP-101,606, are NMDA receptor antagonists
with promising neuroprotective properties. In recombinant NMDA receptors
expressed in Xenopus oocytes, we found that these drugs inhibit NMDA receptors
through a unique mechanism, making the receptor more sensitive to inhibition by
protons, an endogenous negative modulator. These findings support a critical role
for the proton sensor in gating the NMDA receptor and point the way to
identifying a context-dependent NMDA receptor antagonist that is inactive at
physiological pH, but is a potent inhibitor during the acidic conditions that
arise during epilepsy, ischemia and brain trauma.
PMID- 10196582
TI - Inhibition of T-type voltage-gated calcium channels by a new scorpion toxin.
AB - The biophysical properties of T-type voltage-gated calcium channels are well
suited to pacemaking and to supporting calcium flux near the resting membrane
potential in both excitable and non-excitable cells. We have identified a new
scorpion toxin (kurtoxin) that binds to the alpha 1G T-type calcium channel with
high affinity and inhibits the channel by modifying voltage-dependent gating.
This toxin distinguishes between alpha 1G T-type calcium channels and other types
of voltage-gated calcium channels, including alpha 1A, alpha 1B, alpha 1C and
alpha 1E. Like the other alpha-scorpion toxins to which it is related, kurtoxin
also interacts with voltage-gated sodium channels and slows their inactivation.
Kurtoxin will facilitate characterization of the subunit composition of T-type
calcium channels and help determine their involvement in electrical and
biochemical signaling.
PMID- 10196583
TI - Development of the quantal properties of evoked and spontaneous synaptic currents
at a brain synapse.
AB - In many studies of central synaptic transmission, the quantal properties of
miniature synaptic events do not match those derived from synaptic events evoked
by action potentials. Here we show that at mossy fiber-granule cell (MF-gc)
synapses of mature cerebellum, evoked excitatory postsynaptic currents (EPSCs)
are multiquantal, and their amplitudes vary in discrete steps, whereas miniature
(m)EPSCs are monoquantal or multiquantal with quantal parameters identical to
those of the EPSCs. In contrast, at immature MF-gc synapses, EPSCs are
multiquantal, but their amplitudes do not vary in discrete steps, whereas most
mEPSCs seem to be monoquantal with a broad and skewed amplitude distribution. The
results demonstrate that quantal variance decreases during synaptic development.
They also directly confirm the quantal hypothesis of neurotransmission at a
mature brain synapse.
PMID- 10196584
TI - Astrocyte-mediated potentiation of inhibitory synaptic transmission.
AB - We investigated the role of astrocytes in activity-dependent modulation of
inhibitory synaptic transmission in hippocampal slices. Repetitive firing of an
interneuron decreased the probability of synaptic failures in spike-evoked
inhibitory postsynaptic currents (unitary IPSCs) in CA1 pyramidal neurons. The
GABAB-receptor antagonist CGP55845A abolished this effect. Direct stimulation of
astrocytes, or application of the GABAB-receptor agonist baclofen, potentiated
miniature inhibitory postsynaptic currents (mIPSCs) in pyramidal neurons. These
effects were blocked by inhibition of astrocytic calcium signaling with the
calcium chelator BAPTA or by antagonists of the ionotropic glutamate receptors.
These observations suggest that interneuronal firing elicits a GABAB-receptor
mediated elevation of calcium in surrounding astrocytes, which in turn
potentiates inhibitory transmission. Astrocytes may therefore be a necessary
intermediary in activity-dependent modulation of inhibitory synapses in the
hippocampus.
PMID- 10196585
TI - Light and circadian rhythmicity regulate MAP kinase activation in the
suprachiasmatic nuclei.
AB - Although the circadian time-keeping properties of the suprachiasmatic nuclei
(SCN) require gene expression, little is known about the signal transduction
pathways that initiate transcription. Here we report that a brief exposure to
light during the subjective night, but not during the subjective day, activates
the p44/42 mitogen-activated protein kinase (MAPK) signaling cascade in the SCN.
In addition, MAPK stimulation activates CREB (cAMP response element binding
protein), indicating that potential downstream transcription factors are
stimulated by the MAPK pathway in the SCN. We also observed striking circadian
variations in MAPK activity within the SCN, suggesting that the MAPK cascade is
involved in clock rhythmicity.
PMID- 10196586
TI - Zebrafish Clock rhythmic expression reveals independent peripheral circadian
oscillators.
AB - The only vertebrate clock gene identified by mutagenesis is mouse Clock, which
encodes a bHLH-PAS transcription factor. We have cloned Clock in zebrafish and
show that, in contrast to its mouse homologue, it is expressed with a pronounced
circadian rhythm in the brain and in two defined pacemaker structures, the eye
and the pineal gland. Clock oscillation was also found in other tissues,
including kidney and heart. In these tissues, expression of Clock continues to
oscillate in vitro. This demonstrates that self-sustaining circadian oscillators
exist in several vertebrate organs, as was previously reported for invertebrates.
PMID- 10196587
TI - Clock controls circadian period in isolated suprachiasmatic nucleus neurons.
AB - The suprachiasmatic nucleus (SCN) is the master circadian pacemaker in mammals,
and one molecular regulator of circadian rhythms is the Clock gene. Here we
studied the discharge patterns of SCN neurons isolated from Clock mutant mice.
Long-term, multielectrode recordings showed that heterozygous Clock mutant
neurons have lengthened periods and that homozygous Clock neurons are arrhythmic,
paralleling the effects on locomotor activity in the animal. In addition, cells
in dispersals expressed a wider range of periods and phase relationships than
cells in explants. These results suggest that the Clock gene is required for
circadian rhythmicity in individual SCN cells and that a mechanism within the SCN
synchronizes neurons and restricts the range of expressed circadian periods.
PMID- 10196588
TI - Lateral inhibition in the inner retina is important for spatial tuning of
ganglion cells.
AB - The center-surround receptive-field organization in retinal ganglion cells is
widely believed to result mainly from lateral inhibition at the first synaptic
level (in the outer retina). Inhibition at the second synaptic level (in the
inner retina) is thought to mediate more complex response properties. Here we
show that much of the sustained surround antagonism in certain on-center ganglion
cells results from lateral inhibition in the inner retina, via GABAergic amacrine
cells, and that the lateral conduction of this signal requires voltage-gated
sodium currents. Blocking lateral inhibition in the inner retina eliminates the
preference of small-center ganglion cells for small stimuli but has little effect
on ganglion cells with large receptive-field centers. These results illustrate
how lateral inhibition at successive synaptic stages can selectively control the
size of neural receptive-field centers.
PMID- 10196589
TI - Transduction of temporal patterns by single neurons.
AB - As our ability to communicate by Morse code illustrates, nervous systems can
produce motor outputs, and identify sensory inputs, based on temporal patterning
alone. Although this ability is central to a wide range of sensory and motor
tasks, the ways in which nervous systems represent temporal patterns are not well
understood. I show here that individual neurons of the lobster pyloric network
can integrate rhythmic patterned input over the long times (hundreds of
milliseconds) characteristic of many behaviorally relevant patterns, and that
their firing delays vary as a graded function of the pattern's temporal
character. These neurons directly transduce temporal patterns into a neural code,
and constitute a novel biological substrate for temporal pattern detection and
production. The combined activities of several such neurons can encode simple
rhythmic patterns, and I provide a model illustrating how this could be achieved.
PMID- 10196590
TI - Plasticity of temporal information processing in the primary auditory cortex.
AB - Neurons in the rat primary auditory cortex (A1) generally cannot respond to tone
sequences faster than 12 pulses per second (pps). To test whether experience can
modify this maximum following rate in adult rats, trains of brief tones with
random carrier frequency but fixed repetition rate were paired with electrical
stimulation of the nucleus basalis (NB) 300 to 400 times per day for 20-25 days.
Pairing NB stimulation with 5-pps stimuli markedly decreased the cortical
response to rapidly presented stimuli, whereas pairing with 15-pps stimuli
significantly increased the maximum cortical following rate. In contrast, pairing
with fixed carrier frequency 15-pps trains did not significantly increase the
mean maximum following rate. Thus this protocol elicits extensive cortical
remodeling of temporal response properties and demonstrates that simple
differences in spectral and temporal features of the sensory input can drive very
different cortical reorganizations.
PMID- 10196591
TI - Visual self-motion perception during head turns.
AB - Extra-retinal information is critical in the interpretation of visual input
during self-motion. Turning our eyes and head to track objects displaces the
retinal image but does not affect our ability to navigate because we use extra
retinal information to compensate for these displacements. We showed observers
animated displays depicting their forward motion through a scene. They perceived
the simulated self-motion accurately while smoothly shifting the gaze by turning
the head, but not when the same gaze shift was simulated in the display; this
indicates that the visual system also uses extra-retinal information during head
turns. Additional experiments compared self-motion judgments during active and
passive head turns, passive rotations of the body and rotations of the body with
head fixed in space. We found that accurate perception during active head turns
is mediated by contributions from three extra-retinal cues: vestibular canal
stimulation, neck proprioception and an efference copy of the motor command to
turn the head.
PMID- 10196593
TI - Evaluation of red light camera enforcement in Oxnard, California.
AB - Red light cameras are increasingly being used to supplement police efforts to
enforce against noncompliance with traffic signals--a substantial contributing
factor in urban motor vehicle crashes. Camera enforcement is intended to modify
driver behavior through both general deterrence and punishment of individual
violators. A before/after quasi-experimental design with controls was employed to
evaluate the influence of a red light camera enforcement program on red light
violation rates in the city of Oxnard, CA. A total of 14 intersections (nine
camera sites, three non-camera sites, and two control sites) were studied.
Overall, the red light violation rate was reduced approximately 42% several
months after the enforcement program began. Increases in driver compliance with
red lights were not limited to the camera-equipped intersections but spilled over
to nonequipped intersections as well. Results of public opinion surveys conducted
approximately 6 weeks before, 6 weeks after, and 6 months after the camera
enforcement program began indicated that nearly 80% of Oxnard residents support
using red light cameras as a supplement to police efforts to enforce traffic
signal laws.
PMID- 10196592
TI - The anatomy of conscious vision: an fMRI study of visual hallucinations.
AB - Despite recent advances in functional neuroimaging, the apparently simple
question of how and where we see--the neurobiology of visual consciousness-
continues to challenge neuroscientists. Without a method to differentiate neural
processing specific to consciousness from unconscious afferent sensory signals,
the issue has been difficult to resolve experimentally. Here we use functional
magnetic resonance imaging (fMRI) to study patients with the Charles Bonnet
syndrome, for whom visual perception and sensory input have become dissociated.
We found that hallucinations of color, faces, textures and objects correlate with
cerebral activity in ventral extrastriate visual cortex, that the content of the
hallucinations reflects the functional specializations of the region and that
patients who hallucinate have increased ventral extrastriate activity, which
persists between hallucinations.
PMID- 10196594
TI - Police officers' detection of breath odors from alcohol ingestion.
AB - Police officers frequently use the presence or absence of an alcohol breath odor
for decisions on proceeding further into sobriety testing. Epidemiological
studies report many false negative errors. The current study employed 20
experienced officers as observers to detect an alcohol odor from 14 subjects who
were at blood alcohol concentrations (BACs) ranging from zero to 0.130 g/dl. Over
a 4 h period, each officer had 24 opportunities to place his nose at the terminal
end of a 6 in. tube through which subjects blew. Subjects were hidden behind
screens with a slit for the tube to prevent any but odor cues. Under these
optimum conditions, odor was detected only two-thirds of the time for BACs below
0.08 and 85% of the time for BACs at or above 0.08%. After food consumption,
correct detections declined further. Officers were unable to recognize whether
the alcohol beverage was beer, wine, bourbon or vodka. Odor strength estimates
were unrelated to BAC levels. Estimates of BAC level failed to rise above random
guesses. These results demonstrate that even under optimum laboratory conditions,
breath odor detection is unreliable, which may account for the low detection rate
found in roadside realistic conditions.
PMID- 10196595
TI - Characteristics of traffic crashes among young, middle-aged, and older drivers.
AB - An overview of the characteristics of traffic crashes among young, middle-aged
and older drivers is presented. The results suggest that the youngest and the
oldest drivers were more likely to be considered at-fault. With respect to crash
characteristics, older drivers were less likely to have crashes involving driver
fatigue, during the evening and early morning, on curved roads, during adverse
weather, involving a single vehicle, and while traveling at high speeds.
Conversely, older drivers were over-represented in crashes at intersections
and/or involving failure to yield the right of way, unseen objects, and failure
to heed stop signs or signals. Crashes occurring while turning and changing lanes
were also more common among older drivers. Alcohol was less likely to be a factor
in traffic crashes involving older adults. Synthesizing these results led to the
conclusion that the primary problem with the young is risk-taking and lack of
skill. The strength of older drivers lies in their aversion to risk, but
perceptual problems and difficulty judging and responding to traffic flow often
counterbalance this attribute.
PMID- 10196596
TI - Preventing drowsiness accidents by an alertness maintenance device.
AB - The reported experiment investigated in an advanced driving simulator whether
drivers' alertness can be maintained in drowsiness-inducing conditions by a
special game-like system, a 'gamebox'. Drowsiness was assessed by self-rating and
eye-closures. Mental effort was assessed by a subjective workload rating scale
and by a physiological measure (the 0.1 Hz component of heart rate). Driving
quality and safety were assessed by steering movements, time-to-line crossings,
and by the occurrence of safety-related driving errors--solid line crossings,
driving off-road incidents and accidents. When driving with the gamebox, drivers
reported a lower degree of drowsiness and fewer instances of sleep episodes as
compared to a control condition. Driving with the device resulted in fewer
incidents and accidents, and these occurred later in the session. The quality of
vehicle control deteriorated progressively over the course of the session, but
less so in the gamebox condition. Hence, the results corroborate the notion that
mental activity counteracts drowsiness in prolonged driving.
PMID- 10196597
TI - An aggregate level analysis of the socioeconomic correlates of drink driving
offenders.
AB - Research within urban sociology and social geography has discussed the relation
between the spatial or aggregate level distribution of various social and
demographic variables and a wide range of social problems. This paper takes the
spirit of these studies as a starting point and applies methods of social area
analysis to study drink driving offender rates within the Sunshine Coast-Brisbane
Gold Coast conurbation. The major findings of the paper are that at the aggregate
level there is a strong correlation between rates of drink driving offenders and
particular social and demographic factors. As such the findings support existing
studies that have identified given social characteristics of drink drivers. In
addition, the findings also illustrate the need to consider a range of aggregate
social and demographic variables in future research.
PMID- 10196598
TI - Effects of changes in travel patterns on highway fatalities.
AB - This paper estimates the number of deaths that may have been avoided in 1995
because of changes in selected travel patterns during the period from 1969 to
1995 in the US. Four travel patterns are considered, including distributions of
travel between urban and rural areas, between interstates and other roadways,
between night and day time hours, and between female and male drivers. At the
1995 mobility level, changes in the selected travel patterns during the period
from 1969 to 1995 may have avoided up to 9970 deaths in 1995 alone. These deaths
avoided represent over 12% of the total number of deaths avoided in 1995 as a
result of overall improvements in highway safety during the same period in this
country.
PMID- 10196599
TI - The prevalence of non-standard helmet use and head injuries among motorcycle
riders.
AB - OBJECTIVES: This study examined the prevalence of non-standard helmet use among
motorcycle riders following introduction of a mandatory helmet use law and the
prevalence of head injuries among a sample of non-standard helmet users involved
in motorcycle crashes. METHODS: Motorcycle rider observations were conducted at
29 statewide locations in the 2 years following the introduction of the mandatory
helmet use law in January, 1992. Medical records of motorcyclists who were
injured in 1992 for whom a crash report was available and for whom medical care
was administered in one of 28 hospitals were reviewed. Chi-squares and analysis
of variance were used to describe differences between groups. RESULTS: Prevalence
of non-standard helmet use averaged 10.2%, with a range across observation sites
from 0 to 48.0%. Non-standard helmet use varied by type of roadway, day of week,
and time of day. Injuries to the head were more frequent and of greater severity
among those wearing non-standard helmets than both those wearing no helmet and
those wearing standard helmets. CONCLUSIONS: Non-standard helmets appear to offer
little head protection during a crash. Future study is needed to understand the
dynamics leading to head injury when different types of helmets are worn.
PMID- 10196600
TI - Impacts of culture on driver knowledge and safety device usage among Hispanic
farm workers.
AB - This study examines Hispanic migrant farm workers' driving behaviors and
knowledge of the laws. These laborers worked and drove in California's
agricultural region up to 8 months a year. Results are based on 167 face-to-face
interviews conducted in Spanish at five labor camps and 126 observations
conducted at these same camps in California. Most drivers were male licensed
drivers (79%), who learned to drive at ages 8-14 in Mexico (42%). Those licensed
in Mexico versus the US received more citations and unlicensed drivers were rated
with poor driving skills. Drivers reported 'always' using seat belts (86%), yet
admitted not buckling up within the previous 2 months. Observational data showed
that only 37% used belts and 55% of drivers riding alone were belted. Reasons for
non-use reflected cultural and economic issues and lack of effective media safety
campaigns for this group. Most (75%) drivers with children (< 4 years) said they
used child safety seats and others with 1+ children (< 4 years) used no safety
seats (20%) or only one seat (53%). Observations showed that regardless of the
number of riders aged 0-4, the number of car seats never exceeded one. In 66% of
the cars where a single child was carried and where two children were carried, no
car seats were used. In all of these cases there were other passengers and
drivers who were not belted.
PMID- 10196601
TI - Executing effective road safety advertising: are big production budgets
necessary?
AB - Twelve (12) road safety television commercials (TVCs) ranging in production costs
from $A15,000 to $A250,000 (current prices) were evaluated using standard
advertising pre-test procedures. The twelve ads covered four road safety
behaviours (speeding; drink driving; fatigue; and inattention), and included a
variety of executional types within and across behaviours. One ad in each of the
four behaviours was an expensive TAC and ($A200,000 or more). The testing
procedure assessed respondents' self-reported impact of the ad on their future
intentions to comply with the road safety behavior advocated in the ad. Just
under 1000 appropriately screened motor vehicle drivers license holders were
recruited via street intercept methods and randomly allocated to one of the
twelve and exposure conditions. The results showed that while the two best
performing ads were highly dramatic TAC ads showing graphic crash scenes, these
were also the most expensive ads to produce, and, being 60 and 90 s, the most
expensive to air. In several cases, 30 s low cost talking heads testimonials
performed equally as well as their far more expensive counterparts. We conclude
that big production budgets may not be necessary to create effective road safety
advertising.
PMID- 10196602
TI - Estimation of expected utility gained from the helmet law in Taiwan by quality
adjusted survival time.
AB - The objective of this study was to empirically estimate the expected utility
gained from the implementation of the 1997 helmet law in Taiwan by using quality
adjusted survival time (QAST). We randomly selected 400 out of 8221 registered
cases of head injury and successfully interviewed 99 cases with the index of
health-related quality of life (IHRQ). The function of IHRQ was then multiplied
with the corresponding survival function to obtain the QAST for head injury. The
total utility gained from the helmet law in Taipei within 1 year was estimated by
multiplying the expected loss of utility per patient with the number of prevented
cases. The results showed that after 80 months of follow-up, the QAST of the
injured population was 66.3 quality-adjusted life-months (QALMs), while that of
the reference population was 78.7 QALMs. We extrapolated the QAST for total life
expectancy by simulating the survival of head injury cases using the life table
data from the general population. The life-long utility loss of a head injury
case was found to be 4.8 quality-adjusted life-years (QALY). The number of
prevented cases during the first year of enforcement of the helmet law was
estimated to be 1300 cases in Taipei, which amounted to 6240 QALYs gained. For
lack of data, we were unable to calculate the possible gain from helmet on
reduction of severity among nonfatal cases with head injury, and the estimation
was only a lower bound. We concluded that the QAST approach is a feasible
approach applicable to health policy decision-making, especially in cost-utility
analysis.
PMID- 10196603
TI - Can injury prevention efforts go too far? Reflections on some possible
implications of Vision Zero for road accident fatalities.
AB - The Swedish National Road Administration has launched a long term vision of a
road transport system in which nobody is killed or sustains an injury resulting
in permanent impairment (Vision Zero). This paper examines some possible
implications of Vision Zero for traffic fatalities. The main points of the paper
can be summarised as follows: An objective of eliminating traffic deaths can be
interpreted as an application of a general principle of minimising mortality.
Minimising overall mortality implies that a survival lottery must be introduced,
at any rate as long as there is a shortage of organs for transplants. A survival
lottery is a scheme in which people are drawn at random to sacrifice their life
for the benefit of others. An objective of eliminating a certain cause of death,
like traffic accidents, may be so expensive to realise that there is so much less
resources available to control other causes of death that general mortality
increases. Several analyses of the relationship between income per capita and
general mortality based on Norwegian data document a negative relationship
between income and mortality. The loss of income that induces an additional
statistical death, due to economic inefficiency, is estimated to between 25 and
317 million NOK (3.8-47.5 million US dollars). These estimates are in line with
those of most previous studies. No study of the relationship between income and
mortality fully satisfies commonly used criteria of causality. However, the
balance of evidence suggests that the relationship between income and mortality
is a causal one. A hypothetical programme designed to implement Vision Zero for
traffic fatalities was developed and its effects on the number of fatalities
estimated. Implementing the whole programme could reduce the number of traffic
deaths in Norway from about 300 per year to about 90 per year. Applying the
lowest estimate of the income loss that induces an additional death (25 million
NOK), it was estimated that implementing the entire hypothetical Vision Zero
programme would increase general mortality by about 1355. This would lead to a
net increase of about 1145 deaths per year (1355 minus 210 prevented traffic
deaths). The analyses presented in this paper show that the possibility cannot be
ruled out that a massive effort to eliminate traffic deaths would be
counterproductive in terms of overall mortality. This possibility must be
regarded as a moral dilemma by advocates of Vision Zero, who have invoked the
ethical principle that 'one must always do everything in one's power to prevent
death or serious injury' to justify the vision.
PMID- 10196605
TI - Primary malignant lymphoma of the appendix (a case report and review of the
literature).
AB - Authors report a case of a 29-year-old male with primary malignant lymphoma of
the appendix with involvement of lymph nodes in the mesenteries. Surgical
intervention was performed, adjuvant chemotherapy was applied. No recurrences,
metastases or complaints occurred after one year of follow-up. The case is of
interest due to the clinical and histopathological diagnostic problems as well as
the dimension of the metastatic lymph node in the ileal mesentery.
PMID- 10196606
TI - The importance of arthroscopy in diagnosing synovial haemangioma of the knee
joint.
AB - In connection with one of their cases, authors call attention to the importance
of differential diagnosis in synovial haemangioma of the knee joint, a rare
condition. They also give a survey of its clinical, radiological and pathological
features, review the literature on the topic, with special emphasis on the
importance of arthroscopy in making the clinical diagnosis, and describe the
treatment applied in their case.
PMID- 10196604
TI - Changing diagnostic and therapeutic approaches to the 'Ogilvie syndrome'.
AB - The only thing that has remained unchanged about the genuinely described 'Ogilvie
syndrome' is its name. Recently it was considered to be an acute colonic
pseudoobstruction, a clinical entity mimicking the mechanic ileus of the distal
large intestine, without organic obstruction. It is almost always secondary to
other diseases. Not all details of the pathogenesis are known, but it has become
clear that the direct factor leading to the disturbance of the motility is a
vegetative imbalance. X-ray findings are highly characteristic and critical in
the planning of treatment. The danger for the patients is the progression of the
state or the long duration of the process. Conservative treatment is suitable
only for early cases, without complications. In case of failure non-invasive
endoscopic or endoscopically assisted minimally invasive procedures may be
mandatory. These methods have seen rapid advance in recent years. Uncertain
diagnoses or complications call for open surgery. Cecostomy is the solution of
choice anyway. The mortality is high in this group of elderly polymorbid
patients. Authors compare six of their cases with data collected from the
literature.
PMID- 10196607
TI - Re-evaluation of the role of impedance plethysmography in the diagnosis of deep
vein thrombosis in surgical patients.
AB - The clinical diagnosis of deep-vein thrombosis (DVT) is nonspecific and
nonsensitive. As a result invasive and non-invasive laboratory tests are needed.
In order to detect the diagnostic value of impedance plethysmography (IPG), a
widely used non-invasive laboratory test, a prospective clinical trial was
performed to compare IPG with color Doppler-ultrasonography (CDUS) and
venography. Seventy-six (41 female, 35 male) high-risk abdominal surgery patients
were included in the study. IPG and CDUS were performed preoperatively. During
the postoperative period IPG, CDUS and venography were carried out. The
sensitivity, specificity, positive predictive value (PPV), negative predictive
value (NPV) and accuracy of IPG were all determined. The preoperative IPG was
positive in 32 patients, being (+) in 29 patients postoperatively. On the other
hand, two of the 29 postoperative IPG (+) patients had DVT diagnosed
postoperatively by CDUS and venography. One of 47 IPG (-) patients had DVT
diagnosed postoperatively. According to these findings, the sensitivity of IPG
was 67%, specificity 63%, and PPV, NPV and accuracy were 7%, 98% and 63%,
respectively. Our study showed that IPG was not a reliable non-invasive
laboratory method in the diagnosis and screening of DVT of the lower extremity.
PMID- 10196608
TI - Overview of our 13-year-long experience with cochlear implants.
AB - Authors give account of their 13-year-old experience of cochlear implantation.
Their results with different devices as well as some observations regarding
fitting and rehabilitation are also discussed.
PMID- 10196609
TI - Serologic examinations in acute appendicitis.
AB - Authors studied the formation of endotoxic antibody level in healthy adults and
in patients with appendicitis with a technique (indirect haemagglutination) not
used till now. They found the antibody level against endotoxin to be increased in
91% of their patients in the postoperative period. Decrease in the antibody level
against endotoxin was observed in two patients with gangrenous appendicitis and
two patients with perforated appendicitis. Summarizing their results, authors
consider mixed (aerobic, anaerobic) infection to be of decisive importance in the
development of acute appendicitis, contributing to the weakened immune response
of the host.
PMID- 10196610
TI - Reverse two-stage procedure in the surgical treatment of esophageal cancer.
AB - Authors have performed 266 one-stage resections and 6 reversed two-stage
operations for the treatment of esophageal cancer during a 10-year-period. In six
cases first a substernal bypass with colon or stomach was carried out while the
tumourous esophagus was removed only 3-4 weeks later from a right thoracic
approach. All six patients recovered. The reverse two-stage operation for
esophageal cancer can be suggested with rare indications (pulmonary abscess,
previous abdominal operations, severe malnutrition, etc.) and it is only
justified when the advantage gained by increased operability and decreased
morbidity and/or mortality is higher than the disadvantage ensuing from
oncological, financial and patient demanding considerations.
PMID- 10196611
TI - Pharyngeal dysphagia caused by isolated myogen dystrophy of musculus
cricopharyngeus.
AB - Five patients suffering from idiopathic cricopharyngeal dysfunction (without
Zenker's diverticulum) were treated surgically. Together with
cricopharyngeomyotomy biopsies were taken at the level of the cricopharyngeus.
Histological, enzyme hystochemical and electronmicroscopic examinations were
performed on all patients. In two cases the histology revealed myogen dystrophy
(presence of necrosis, myophagocytosis, abnormal fiber structure, basophilic
fibers, fibrosis, mild cellular reaction and predominancy of fiber type I). Since
the complete patient evaluation (clinical features, electromyography, serum
creatinin phosphokinase level, etc.) could rule out any general, muscle
disorders, the cause of the idiopathic pharyngeal dysfunction must have been in
these two cases an isolated myogen dystrophy of the cricopharyngeus.
PMID- 10196612
TI - Functional improvement after knee arthroplasty without resurfacing of patella.
AB - There has been no universal agreement so far regarding the necessity of patellar
resurfacing in total knee arthroplasty. As resurfacing has been reported to be
associated with high incidence of complications, this practice has been avoided
in our Department. A report is given on the analysis of the functional outcome of
60 knee arthroplasties without patellar resurfacing in 53 patients (7 bilateral)
followed up for twelve to thirty months, with special regard to the functions
closely related to patelloformal articulation. The underlying diagnosis was
osteoarthritis in 78.3%, rheumatoid arthritis in 13.3%, and posttraumatic
arthritis in 8.3% of the patients. Graded according to the modified knee-rating
system of the Hospital for Special Surgery, excellent or good results were
obtained in the case of 55 knees (91.6%) and the mean score improved from 53.6
points preoperatively to 82.6 points following arthroplasty. Subjective and
objective functional assessment of stair climbing and transfer activities have
shown no functional deficit attributed to the patellofemoral joint of the
replaced knee.
PMID- 10196613
TI - Methods helping the diagnosis of "acute scrotum" based on medical practice in our
department.
AB - Authors have analysed the case records of their patients admitted in the last 2.5
years. The color-doppler US is stated to be the most efficient method in
differential diagnostics, but the conventional ultrasound + Doppler +
scintigraphy can also help in establishing quick and reliable diagnosis as it has
been proved in practice.
PMID- 10196614
TI - Eight-year experience in treatment of hemorrhoidal disease.
AB - During an eight-year period 887 patients with symptoms of hemorrhoids were
treated at the Department of Surgery and Outpatient Care of the Vaszary Kolos
County Hospital, Esztergom. 178 patients with first degree hemorrhoids received
only conservative treatment. Rubber band ligation (RBL) which can be performed on
outpatients was applied in 324 patients with first, second and third degree
hemorrhoids. Thrombosed external hemorrhoids were treated by excision in 215
patients. Hemorrhoidectomy (H) was mainly carried out in 91 cases for treatment
of circular 3rd and 4th degree nodules involving complications. More than 80 per
cent of the patients receiving rubber band ligation and hemorrhoidectomy were
followed up. 65% of the RBL group and 85% of the H group were symptom free, while
76% of the RBL group and 91% of the H group showed great improvement after the
treatment. Personal results, complications, and review of the literature are
discussed in detail.
PMID- 10196615
TI - Unstable pelvic fractures in children.
AB - A total of 3561 freshly injured children received treatment at the paediatric
trauma department of the National Institute of Traumatology between 1984 and
1994. Out of these 38 (approx. 1%) had pelvic fractures. Based on the
classification of Tile and Laer, 15 pelvic fractures were diagnosed to be
unstable, from which 8 were polytraumatised, 4 shocked and 1 was a casualty. Run
downs could be considered as the main cause of these fractures. Conservative
treatment was provided for 13 unstable cases (bed rest: 5, band suspension: 1,
femur skeletal traction: 4, femur traction and band suspension: 3). Surgery was
performed in 2 cases (symphysis cerclage: 1, acetabulum plate o.s.: 1). Eleven
patients were called in for late controls (after 3 years). Subsequent
complications were: pain: 3, limb shortening: 4, lumbal scoliosis: 1, minor
pelvic deformations: 4, partial necrosis of caput femoris: 2. The subjective
complaints of 3 adolescent cases seem to be small in number, however, it is a
fair assumption that the control period of 3-6 years later is not enough to form
a comprehensive conception on the nature of early degenerative deformations
occurring later, e.g. during adulthood. Because of further surgeries and
examinations, correct traction and suspensional treatment can only be carried out
with great difficulties regarding children. Therefore, posterior stabilisation of
the pelvic ring must be planned with percutaneous sacroiliac pinning or screwing
in unstable cases.
PMID- 10196616
TI - How effective is the routine mediastinal blockdissection in the surgery of non
small cell lung cancer?
AB - The performance of ipsilateral mediastinal blockdissection as a routine in every
non-small cell lung cancer (NSCLC) operation gives us a chance to judge the
accuracy of the preoperative CT examination. The accuracy rate of the CT in our
316 cases was 70.6%, the false positive rate was 69.6%, the false negative rate
was 18.2%. Taking into account the 18.2% false negative rate and the slightly
better survival of patients operated with routine blockdissection compared to the
survival of a group of patients who had mediastinal blockdissection only if
suspicion of tumour spread arose, we consider the procedure reasonable in every
NSCLC operation.
PMID- 10196617
TI - Biopsy-based diagnosis of prostate cancer in 1290 patients referred for prostate
examination: results according to the PSA level, digital rectal examination and
ultrasonography.
AB - Authors present their retrospective study of 1290 patients referred for prostate
evaluation. The risk of cancer was analysed according to PSA, rectal palpation
and ultrasound examination. Among the 1290 patients, 54.8% had cancer. The risk
of cancer was multiplied by 2.8 when the PSA was between the normal limit and 10
ng/ml, by 7.5 when it exceeded 10 ng/ml, by 4.0 when rectal palpation was
abnormal and by 1.6 when a hypoechogenic zone was present. Although a
hypoechogenic zone does not improve the detection of cancer compared to PSA and
rectal palpation, an increased PSA level even lower than 10 ng/ml indicates
biopsies.
PMID- 10196618
TI - Data to the clinical manifestation of the Krukenberg tumour.
AB - Ovarian cancer is one of the most frequent malignant tumours in the female
population. The screening of this tumour type is unsolved. The tumours are
usually diagnosed in the advanced stage; thus the results of survival are
unfavourable. Their histopathological appearance has a wide variety, with the
occurrence of numerous metastatic forms. In these metastatic cases the choice of
treatment is more difficult and prognosis is also worse. Among the metastatic
tumours, the primary tumours of the gastrointestinal tract occur the most
frequently. They are known as the Krukenberg tumour. Authors present two cases of
Krukenberg tumours in order to summarize our knowledge on this rare tumour type
and to give some practical advice.
PMID- 10196619
TI - Ureter and bladder replacement following radical cystectomy.
AB - During the course of Hautmann-type bladder replacement, left sided ureter damage
necessitated ureter replacement as well, modifying the removal of the ileum
bladder. The proximal 20 cm length of the 70 cm long isolated ileum portion was
not detubularized; instead it was slipped through the mesosigma and mesocolon to
the left side of the colon and the left ureter stub was anastomized without
tautness to the ileum according to Le Duc. The implantation of the right ureter
was accomplished according to Hautmann. For similar cases authors recomment this
procedure, since neither stricture, nor reflux could be detected at later
examinations.
PMID- 10196620
TI - Organ-preserving surgery of renal cell carcinoma: report of four cases.
AB - Authors removed the renal tumour of four patients by means of resection in an
organ-preserving manner. Of the four patients, one had bilateral carcinoma. The
right-sided carcinoma of this patient was removed by resection while the other
kidney was removed radically, by transabdominal approach. In three of the four
cases which were in the process of stages T1 and N0M0, organ-preserving surgery
was performed in the presence of intact opposite kidneys. Authors point out the
fact that the resection method might be indicated even in the case of early (T1)
stage tumours with intact opposite side kidneys. Furthermore, they do not
recommend the enucleation of renal carcinomas for the surgical treatment of
kidney tumours, since experimental studies have proved that these tumours can be
transferred into the parenchyma of the kidney through the pseudocapsule of the
tumour.
PMID- 10196621
TI - Bilateral ureteric replacement with ileum.
AB - In connection with a report of a case, authors discuss in outline the
possibilities of ureter replacement. If both the ureters are injured, they can be
substituted with one single segment of the intestine, as it happened in their
case. Authors raise the idea that a longer segment of the intestine used for
substitution provides sufficient capacity and isoperistaltic function, and this
may protect from the negative effects of possible vesicoileal reflux. In this
case, the reflux does not spread to the kidneys even if the ureteroileal was not
made with anti-reflux technique.
PMID- 10196622
TI - Kidney oncocytoma.
AB - Authors review the case history of three patients with kidney tumours which had
been surgically removed. In two of the cases radical nephrectomy while in one,
organ-preserving surgery was performed. In all the cases histology revealed
benign kidney tumours--oncocytomas. In light of the available literature authors
indicate that preoperative diagnosis is almost impossible. Furthermore, it is
their opinion that this benign kidney tumour has a less frequent occurrence than
earlier thought.
PMID- 10196623
TI - Pancreas, diabetes mellitus and pancreatic transplantation--a retrospective
survey.
AB - The administration of exogenous insulin ameliorated the symptoms and increased
the life expectancy of insulin dependent diabetic patients, but could not cure or
prevent the devastating complications including retinopathy, nephropathy and
angiopathy. It was recognised that despite insulin therapy, the severity and
frequency of the degenerative late complications are still high in patients
suffering from diabetes mellitus. The recognition of the increased frequency of
and complications accompanying the disease has intensified efforts by scientists
to find the form of pancreatic tissue to be transplanted and the suitable site in
a bid to secure an insulin producing graft. This review presents an update in
pancreatic organ and fragment transplantation. The history of the pancreas is
also brought into limelight to show the long, hard and exciting path pancreas and
diabetes mellitus have both gone through. An account is also given of
experimental and clinical pancreatic whole organ/fragment transplantation
including transplantation sites, the evaluation of the viability of pancreatic
grafts and the complications of transplantation. Pancreatic islet transplantation
is not discussed.
PMID- 10196625
TI - Alternative medicine--how safe is it?
PMID- 10196624
TI - Famous names in toxicology. Inoculators and vaccinators of the 18th century II.
Dr Thomas Dimsdale of Hertford.
PMID- 10196626
TI - Diethylene glycol poisoning associated with paracetamol liquid formulations.
PMID- 10196627
TI - Serious adverse reactions to anorectic agents.
PMID- 10196628
TI - Adverse effects of corticosteroids.
PMID- 10196629
TI - Expression of delta-endotoxin cryIA(c) gene of Bacillus thuringiensis in
Escherichia coli and Streptomyces lividans.
AB - The cryIA(c) gene of Bacillus thuringiensis was isolated from plasmid pOS1000. In
order to obtain a proper cloning site and open reading frame, some DNA sequences
preceding the initiating codon of the gene were replaced by synthetic
oligonucleotide sequences. The isolated cryIA(c) was cloned into E. coli
expression vector pKK223-3, and production of CryIA(c) protein was detected after
induction by IPTG. A recombinant plasmid, pHZ1256, was constructed by insertion
of the cryIA(c) gene into Streptomyces vector pHZ1272. pHZ1256 was introduced
into Streptomyces lividans, and the production of CryIA(c) protein was confirmed
by Western blotting after thiostrepton induction. A bioassy experiment showed
that the CryIA(c) protein produced by E. coli and S. lividans caused 93% and 57%
mortality to Plutella xylostella, respectively.
PMID- 10196630
TI - Study on the genetic determinants responsible for expression and assembly of CS3
fimbriae.
AB - Colonization factor antigens (CFAs) are important virulent factors and protective
antigens of enterotoxigenic Escherichia coli (ETEC). Among the known CFAs of
human origin, CS3 is a major fimbriae antigen. To study the genes associated with
the expression and assembly of CS3 is a key step to delineate the regulating
mechanism of expression and assembly of the fimbriae. In this paper we analyzed
the restriction map of the CS3 genetic determinant and successfully cloned the
CS3 subunit gene and the region encoding the auxiliary proteins. Expression
results of the recombinant plasmids in minicells showed that the genetic
determinant of CS3 fimbriae encodes six polypeptides with molecular weights 15,
17, 24, 27, 48, and 90 kDa. Western blotting and complementary expression
analysis among the different mutants showed that the 15 kDa/17 kDa proteins
compose the CS3 subunit and the 17 kDa protein is the precursor. The others may
be necessary for the assembly of CS3 fimbriae. The relative locations of various
genes of the CS3 genetic determinant were also determined.
PMID- 10196631
TI - Cloning of 1-aminocyclopropane-1-carboxylate (ACC) synthetase cDNA and the
inhibition of fruit ripening by its antisense RNA in transgenic tomato plants.
AB - A 1.7 kb fragment of ACC synthetase cDNA, one member of the ACC synthetase
multigene family, was amplified from total tomato cDNA through a polymerase chain
reaction (PCR) and cloned in E. coli. Restriction mapping and sequencing analysis
confirmed its fidelity and correctness. The cloned ACC synthetase gene was then
inserted into a binary vector pBin437, in an inverted orientation between the
CaMV 35S promoter with duplicated enhancers and the Nos 3' transcriptional
termination sequence, to construct an expression vector pBACC. Transgenic tomato
plants were obtained by A. tumefaciens-mediated transformation of cotyledons. PCR
detection and Southern blot analysis confirmed the integration of the antisense
ACC synthetase gene in the transformed tomato genome. The results from RT-PCR of
RNAs isolated from transgenic tomato leaves confirmed that antisense ACC
synthetase RNA was synthesized in these transgenic plants. The amount of ethylene
released from transgenic tomato fruits was reduced significantly to about 30% of
that released by non-transformed controls. The inhibition effect of antisense RNA
on fruit ripening was observed in transgenic plants and their progeny (T1). The
shelf life of transgenic tomato fruits was at least 60 days at room temperature
without significant change in hardness and color. After 15-20 days of treatment
of the transgenic fruits with ethylene, most of them reached the ripe stage. The
antisense ACC synthetase gene was inherited as a single gene in the progenies of
transgenic tomatoes determined by T1 progeny analysis, consistent with the
results of Southern blot analysis. Transgenic homozygotes expressing antisense
ACC synthetase RNA showed prolonged shelf life in the T2 progeny.
PMID- 10196632
TI - The effect of environmental conditions and glucose feeding in shaking flask on
glutathione (GSH) production.
AB - The effects of pH, broth volume, initial sugar concentration, ratio of carbon to
nitrogen and phosphorus, and the glucose feeding method on GSH production in a
shaking flask were investigated. The results showed that the proper pH and broth
content for GSH production were 6.0 and 60 ml broth per 500 ml flask,
respectively. The initial glucose concentration distinctly affected the GSH
production; the intracellular GSH content of yeast would decrease when the
initial glucose concentration was beyond 12 g/L. A glucose feeding strategy with
the purpose of controlling the specific growth rate at an expected value was
developed and applied to a 12 hour fermentation with the total glucose
concentration 26.2 g/L; the final cell concentration (DCW) and the intracellular
GSH content could reach 8.78 g/L and 13.6 mg/g, respectively, while the total GSH
in the broth was 119.4 mg/L and the yield of cell to glucose was 0.335 g/g.
PMID- 10196633
TI - Studies on chemical constituents and immunological function activity of hairy
root of Astragalus membranaceus.
AB - Using a large-scale culture technique, the hairy roots of Astragalus membranaceus
were produced with a yield reaching 10 g/L. The results from RP-HPLC detection
showed that the contents of crude saponin and astragaloside i.v. in the hairy
roots were 5.81% and 0.14%, respectively. Six isoflavonoid compounds were also
determined. Polysaccharide analysis showed that the total polysaccharide content
in the hairy roots was 22.97%; of this content, acidic 8.29% and soluble 14.88%.
In comparison with the dry roots, the hairy roots contained higher crude saponin
and soluble polysaccharide contents, similar astragaloside i.v. content and lower
contents of 6 isoflavonoids, total and acidic polysaccharides, showing that the
quality of both types of roots was similar. Regaining the immunity function of
rats with low immunity after feeding the aqueous extract of the hairy roots
produced by large-scale culture showed that its capacity was similar to the dry
roots of A. membranaceus in increasing the immunity function. The results in this
paper give evidence that the hairy roots may be a new source of A. membranaceus.
PMID- 10196634
TI - Oxygen transfer characteristics in the compact callus aggregates of Rhodiola
sachalinensis.
AB - The effective diffusivity of oxygen in compact callus aggregates (CCA) of
Rhodiola sachalinensis was extremely small, varying from 0.34 x 10(-11) to 5.4 x
10(-9) m2/s and increasing with particle diameter. The calculated results
indicated that severe oxygen limitations occurred in the CCA aggregates. However,
the direct determination of the viability of the cells demonstrated that the CCA
aggregates contained a high fraction of viable cells. It was suggested that the
tissue differentiation or plasmodesmata within the CCA aggregates may provide
capillaries for improving transport of oxygen and other nutrients.
PMID- 10196635
TI - Downstream technique study of human tumor necrosis factor alpha and its mutant.
AB - The study of downstream techniques for recombinant human necrosis factor alpha
(rhTNF alpha) and its mutant (Lys2)-rhTNF alpha led to the results of
approximately 50 g wet recombinant E. coli per liter with high expression level
(> 50%) harvested from autocontrolled fed-batch culture in 15 L fermentor (B.
Braun). The rhTNF alpha and (Lys2)-rhTNF alpha expressed are totally soluble.
Followed by the process of ultrasonication, ammonium sulfate precipitation, ion
exchange chromatography (DEAE-sepharose FF, CM-sepharose FF), and molecular sieve
(Sephacryl S-200), a yield of approximately 1 g pure recombinant protein from 1 L
broth is obtained. The purity is up to 98%. The specific activity of rhTNF alpha
and (Lys2)-rhTNF alpha are approximately 1.5 x 10(8) IU/mg and approximately 6 x
10(8) IU/mg, respectively.
PMID- 10196636
TI - Transformation of cortisone acetate using immobilized Arthrobacter simplex cells.
AB - A new cell immobilization method was developed in which cells of Arthrobacter
simplex BY-2-3-51 were immobilized by entrapment with a polyvinyl alcohol
alginate complex carrier. The immobilized cells preparation contains spherical
beads with high mechanical strength and delta 1-dehydrogenase activity. The
activation conditions and enzymatic properties of the immobilized cells were
studied. When the initial substrate concentration was 20 mg/mL, the conversion of
cortisone acetate to prednisone acetate by immobilized cells in the shaken
culture was 98% at 18 hours. The stability of immobilized cells was maintained by
activation at proper times.
PMID- 10196637
TI - A neural network for the optimization of fed-batch glutamic acid production.
AB - A neural network system, which is composed of a simulation subnetwork and an
optimization subnetwork, was constructed to predict and optimize the industrial
fed-batch fermentation of glutamic acid. A data-compression and filtration
network structure was incorporated into the simulation subnetwork to extract
"noise-free" patterns from the input signals. The sole-variant optimization and
the multiple-variant optimization can be easily carried out by the neural network
developed. A satisfactory result has been achieved.
PMID- 10196638
TI - Guidelines, standards and protocols in head and neck cancer: tools not
restraints.
PMID- 10196639
TI - Diabetes and hearing loss.
PMID- 10196640
TI - Bipolar scissor tonsillectomy.
AB - We describe a new technique for tonsillectomy using dual-function scissors that
cut and bipolar coagulate at the same time. The technique shortens operating time
and decreases intra-operative blood loss. Forty patients had their tonsillectomy
performed using this technique. The mean operating time was 5.5 min (SD 2.1) and
mean blood loss was 1.3 ml (SD 3.6). All patients were able to eat and drink on
the same postoperative day and all were discharged the following morning. None of
the patients had primary haemorrhages and two patients (5%) had minor secondary
haemorrhages. We found bipolar scissor tonsillectomy to be a safe technique that
shortens surgery and minimises blood loss without causing increased postoperative
morbidity.
PMID- 10196641
TI - Investigations into the natural history of vestibular schwannomas.
AB - In the period from 1977 to 1996 143 vestibular schwannomas were diagnosed in 138
patients in the County of Aarhus, Denmark. The natural history of vestibular
schwannomas was observed in 50 patients with 52 tumours who did not undergo
immediate surgical removal of their tumour due to small tumour size, advanced
age, poor general health and the patients' refusal of surgery. The management
included serial CT- or MR-imaging and complete otoneurological evaluation. The
imaging interval was between 6 months and 2 years and depended on the recorded
growth rate. Thirty-three (64%) of the tumours showed continuous growth with a
mean growth rate of 1.6 mm/year. In 11 (21%) of the tumours the size was
unchanged and eight (15%) remitted. The last group consisted mainly of the
largest tumours. Among the tumours with positive growth, 15 (45%) had a growth
rate of 1 mm/year or less. Generally, our findings showed that approximately two
thirds of all the tumours did not grow, were getting smaller or had a growth rate
sufficiently small to be simply watched. Additionally, our results suggest that
some symptomatic tumours will grow to a certain point whereupon stagnation or
remission occurs.
PMID- 10196642
TI - Short-term benefits of grommet insertion in children.
AB - It is commonly acknowledged that otitis media with effusion (OME) can cause
behavioural disturbances and that this can be relieved by grommet insertion.
However, this widely-held perception has not been documented in the literature.
In this study parents were asked to complete a short behavioural questionnaire on
the day of the admission and 6 weeks later. A total of 32 children admitted to
the Day Care Unit for insertion of grommets at The Royal National Throat, Nose
and Ear Hospital, London, UK, were recruited. There was a significant behavioural
change, evident by the difference in the scores before and after grommet
insertion (P < 0.001).
PMID- 10196643
TI - Twenty-four hour ambulatory nasal pH monitoring.
AB - The nasal delivery of drugs, both for systemic and local use, is an expanding
field with many drugs being delivered by this route. It is known that changes in
pH can affect drug absorption but there is no data regarding intranasal pH over
time. We present the results of 24-h ambulatory nasal pH monitoring in four
subjects, each of whom had monitoring on two separate occasions. The apparatus
consisted of a pH monitor with two electrodes, thus enabling us to take readings
from 1 and 4 cm behind the anterior end of the inferior turbinate. Measurements
were recorded every 6 s by the posterior electrode and every 30 s by the anterior
electrode. The recording apparatus was worn around the subjects waist. Analysis
of the results showed that there was no diurnal variation and no significant
differences between the subjects. The mean pH from the anterior electrode was
higher than that from the posterior (7.1 versus 6.6). The pH did not fluctuate
with daily activities such as eating, drinking or sleeping. The results are
interesting and may be of importance with regard to the design of formulations
for nasal drug delivery systems.
PMID- 10196644
TI - Trends in the UK contribution to the otolaryngological literature.
AB - Ten leading otolaryngological journals were reviewed with a view to detecting the
UK contribution to the ENT literature from 1985 to 1994. From a total number of
12,293 publications studied 2414 (19.6%) papers were found to originate from
British and Northern Irish otolaryngological departments, with the proportion of
UK papers remaining at around 20% throughout the whole 10-year period. These
papers were fully reviewed and the number of authors, paper type, names of
authors and originating department recorded. Eleven departments were responsible
for 50.2% of the total number of publications with the most prolific author being
responsible for 2.5% (n = 60) of the total number of UK papers. Over the 10-year
period, there has been a significant change towards the publication of more
clinical research at the expense of pure laboratory research in these 10 journals
(chi 2 P < 0.001). There has also been a move towards multiple authorship (three
or more co-authors) over the same period with fewer single-author papers (P <
0.001).
PMID- 10196645
TI - The effect of severity of unilateral vestibular dysfunction on symptoms,
disabilities and handicap in vertiginous patients.
AB - This study compares the symptoms, disabilities and handicap, as assessed by means
of a questionnaire, in two groups of patients with a unilateral peripheral
vestibular disorder: those with a total canal paresis and those with a partial
canal paresis, as judged by the duration parameter using the Fitzgerald Hallpike
caloric test in the absence of optic fixation. The results of the study indicate
that the severity of dizziness, the Dizziness Index (severity x frequency) and
the overall level of disabilities related to visual vertigo are less severe in
unilateral profound or total loss of vestibular function than in unilateral mild
vestibular loss.
PMID- 10196646
TI - The outcome of endoscopic sinus surgery: correlation with computerized tomography
score and systemic disease.
AB - We have prospectively analysed the outcome of patients undergoing endoscopic
sinus surgery for chronic rhinosinusitis in relation to the Lund and Mackay
system of scoring the preoperative computerized tomography scan for extent of
disease, and also investigated the possible links of outcome to the presence or
absence of systemic respiratory tract conditions which may relate to the
pathogenesis of chronic rhinosinusitis. Statistical analysis of the data by chi 2
test, unpaired t-test and logistic regression analysis has shown significant
correlation between outcome at 2 years and preoperative computerized tomography
scan score, but that the most statistically significant factor determining the
success or failure of surgery is the presence of a systemic disease known to
predispose to chronic rhinosinusitis.
PMID- 10196647
TI - Epley's manoeuvre for benign paroxysmal positional vertigo: a prospective study.
AB - The treatment of benign paroxysmal positional vertigo (BPPV) by the Epley,
canalith repositioning, manoeuvre was popularized following clinical reports
which demonstrated a significant success rate. Benign paroxysmal positional
vertigo is considered a self-limiting disease, yet only few authors have analysed
the effect of this manoeuvre in randomized, controlled terms. A prospective 3
year, controlled study of patients with BPPV of long duration (mean = 6 months)
verified its benefit: the recovery course differed significantly between a group
of 31 patients treated with the manoeuvre and a control group of 10 untreated
patients. Symptoms subsided within 72 h in 35% and within a week in 74% of
patients after one session of treatment. Only two treated patients (6.5%) did not
recover versus a 50% failure rate among untreated patients (P = 0.0005). The rate
of recovery was not affected by the duration of symptoms before initiation of
treatment, or by the patient's age and gender.
PMID- 10196648
TI - The effects of oral pseudoephedrine on nasal patency in the common cold: a double
blind single-dose placebo-controlled trial.
AB - A placebo-controlled double-blind randomized trial was carried out to assess the
efficacy of pseudoephedrine in relieving nasal congestion in the common cold.
Fifty-four previously healthy persons who had a common cold for at least 5 days
or less at the start of the study with moderate to severe nasal congestion were
recruited, 52 completed the trial. Following a single dose of oral
pseudoephedrine (60 mg capsule) or placebo, symptoms of congestion improved
significantly compared with placebo at times 60, 90, 120, and 150 min after the
dose. Total nasal minimum cross-sectional area and nasal volume measured by
acoustic rhinometry increased significantly compared to placebo (P = 0.018 and P
= 0.003, respectively) after the dose. There was no significant change in nasal
area as measured by active posterior rhinomanometry after pseudoephedrine
compared to placebo. We conclude that in the acute common cold, a single 60 mg
dose of pseudoephedrine produces significant increases in the dimensions of the
nasal cavity compared to placebo and this is associated with a reduction in the
symptom of congestion.
PMID- 10196649
TI - Immunohistochemical detection of oestrogen and progesterone receptors in salivary
tumours.
AB - The purpose of this study was to determine the oestrogen and progesterone
receptor status of a selection of salivary tumours. Using immunohistochemistry,
we detected nine oestrogen receptor and six progesterone receptor positive
tumours from a sample of 36. One acinic cell carcinoma and two mucoepidermoid
carcinomas demonstrated positivity for both receptors. We suggest that there may
be role for oestrogen manipulation in the management of some salivary tumours.
PMID- 10196650
TI - Streptomycin perfusion of the labyrinth in the treatment of Meniere's disease: a
modified technique.
AB - The ideal surgical procedure for Meniere's disease would combine the high rate of
vertigo control and the good hearing preservation of vestibular nerve section
with the low morbidity of labyrinthectomy. Shea's technique of streptomycin
perfusion of the labyrinth has been modified by making an additional opening into
the posterior semicircular canal in an effort to limit the amount of streptomycin
going into the cochlea. Seventeen patients with definite Meniere's with poor
hearing have had this procedure. Vertigo was controlled in 94% and the hearing
preserved in 55%. Vestibular rehabilitation was not a problem. It is speculated
that hearing preservation would be better if the procedure were not restricted to
those with poor hearing. This method of destruction of the vestibular system
carries the possibility of hearing preservation and maintains the possibility of
cochlear implantation should this ever be required.
PMID- 10196651
TI - The use of two pedicled skin flaps in the surgical treatment of acquired atresia
of the outer ear canal.
AB - Surgical treatment of acquired atresia of the outer ear canal remains in some
cases troublesome. Based on previous experience, we have refined the existing
surgical technique to obtain better results. In four patients we used two
pedicled skin flaps for the treatment of total mature post-inflammatory atresia
of the outer ear canal. We raised two well-vascularized pedicled skin flaps with
the distal 1.5-2 cm thinned to the level of a full-thickness skin graft. All
patients showed complete primary healing with stable coverage and near to
complete air-bone gap closure.
PMID- 10196652
TI - The endoscopic management of sinonasal inverted papillomas.
AB - Sinonasal inverted papillomas are well known for high recurrence rates after
surgery and the risk of malignant change. Recurrent disease occurs because of
inadequate excision as a result of poor exposure and visualization. For these
reasons, aggressive surgery has been advocated-classically a lateral rhinotomy
and en bloc medial maxillectomy. Endoscopic techniques have provided excellent
visualization and a less invasive approach to these tumours. We describe 18
patients with inverted papillomas treated endoscopically at the Singapore General
Hospital since 1993. The presentation, sites of involvement and diagnostic
imaging are presented. All the patients had a minimum follow-up of 18 months with
a mean of 32.8 months. One case of recurrence at the frontal recess is reported.
Endoscopic management is appropriate for the diagnosis, follow-up and treatment
of circumscribed primary and recurrent inverted papillomas.
PMID- 10196653
TI - Nasal pH measurement: a reliable and repeatable parameter.
AB - The nasal mucosal pH is approximately 5.5-6.5, and increases in rhinitis to 7.2
8.3. This knowledge has not led to the widespread measurement of the nasal
mucosal pH as an objective clinical parameter. The purpose of this study was to
assess whether repeatable measures of nasal mucosal pH could be obtained in the
clinical setting. Fifty-four adults without nasal symptoms were prospectively
recruited. Using a semi-disposable antimony pH catheter, the nasal mucosal pH was
measured in four specific areas of the nose and each reading repeated three
times. The patients' age, sex, smoking habits, nasal anatomical variation and
clearest nostril at the time of measurement were also recorded. The data shows
that it is possible to obtain reliable and repeatable values for the pH of the
nasal mucosa (Spearman-Brown R = 0.84). Analysis shows there is no significant
difference between septal and turbinate mucosal pH. Subset analysis implies that
nasal mucosal pH is higher in men then women (P < 0.05). The other variables did
not affect the nasal mucosal pH significantly.
PMID- 10196654
TI - Management of inverted papilloma via Denker's approach.
AB - Denker's approach was used in the management of 78 patients presenting with an
inverted papilloma of the nasal sinus complex between the years 1986 and 1993 at
the University Teaching Hospital in Rotterdam. The recurrence rate was 9% with a
mean follow-up after surgery of 56 months. There was minimal morbidity and no
mortality associated with the procedure. Three patients had a squamous cell
carcinoma associated with the inverted papilloma. The results of our study
indicate that Denker's approach has a similar or lower recurrence rate than an
open external approach to papilloma and is a safe procedure with minimal
morbidity.
PMID- 10196655
TI - Does bismuth subgallate have haemostatic effects in tonsillectomy?
AB - Previous studies have shown that bismuth subgallate added to gauze swabs in
tonsillectomy reduces the time to achieve haemostasis and probably reduces the
risk of postoperative haemorrhage. All these studies have used bismuth subgallate
in combination with adrenaline. In this randomised clinical study we investigated
the effect of bismuth subgallate alone. A total of 204 patients were randomised
into two groups. One hundred and six patients had swabs with bismuth subgallate.
In the control group (n = 98), plain swabs were used. Operating time time to
achieve haemostasis, peroperative blood loss, and incidence of postoperative
haemorrhages were recorded. There were no significant differences between the two
groups. We conclude that the evidence for using bismuth subgallate as a
haemostatic agent in tonsillectomy is weak. The effect observed in previous
studies can probably be ascribed to the effect of adrenaline.
PMID- 10196656
TI - Management of the N0 neck in early cancer of the oral tongue.
AB - Elective treatment of the clinically negative neck in the management of early
oral tongue cancers remains controversial. A retrospective review of 71 patients
with T1, 2 N0M0 squamous cell carcinoma of the oral tongue treated at the Royal
Marsden Hospital was carried out. Cervical nodal recurrence at 2 years was 17% in
the group of patients who received elective neck treatment as compared to 43% in
the group who had observation of the neck and the difference is statistically
significant (P = 0.025). The difference in 5-year survival between the group who
had elective neck treatment and the group who did not (75% versus 65%) was not
statistically significant. Until future research allows us to be more selective
on the basis of a reliable panel of histological and/or biological markers for
propensity to nodal metastases, elective neck treatment should be considered in
the initial management of the patients with early oral tongue cancer.
PMID- 10196657
TI - Re: Endoscopic inferior dacryocystorhinostomy.
PMID- 10196658
TI - Damage pattern as a function of radiation quality and other factors.
AB - An understanding of damage pattern in critical cellular structures such as DNA is
an important prerequisite for a mechanistic assessment of primary radiation
damage, its possible repair, and the propagation of residual changes in somatic
and germ cells as potential contributors to disease or ageing. Important
quantitative insights have been made recently on the distribution in time and
space of critical lesions from direct and indirect action of ionizing radiation
on mammalian cells. When compared to damage from chemicals or from spontaneous
degradation, e.g. depurination or base deamination in DNA, the potential of even
low-LET radiation to create local hot spots of damage from single particle tracks
is of utmost importance. This has important repercussions on inferences from
critical biological effects at high dose and dose rate exposure situations to
health risks at chronic, low-level exposures as experienced in environmental and
controlled occupational settings. About 10,000 DNA lesions per human cell nucleus
and day from spontaneous degradation and chemical attack cause no apparent
effect, but a dose of 4 Gy translating into a similar number of direct and
indirect DNA breaks induces acute lethality. Therefore, single lesions cannot
explain the high efficiency of ionizing radiation in the induction of mutation,
transformation and loss of proliferative capacity. Clustered damage leading to
poorly repairable double-strand breaks or even more complex local DNA
degradation, correlates better with fixed damage and critical biological
endpoints. A comparison with other physical, chemical and biological agents
indicates that ionizing radiation is indeed set apart from these by its unique
micro- and nano-dosimetric traits. Only a few other agents such as bleomycin have
a similar potential to cause complex damage from single events. However, in view
of the multi-stage mechanism of carcinogenesis, it is still an open question
whether dose-effect linearity for complex primary DNA damage and resulting fixed
critical cellular lesions translate into linearity for radiation-induced cancer.
To solve this enigma, a quantitative assessment of all genotoxic and harmful non
genotoxic agents affecting the human body would be needed.
PMID- 10196659
TI - Repair of ionizing radiation damage in mammalian cells. Alternative pathways and
their fidelity.
AB - Ionizing radiation causes a variety of types of damage to DNA in cells, requiring
the concerted action of a number of DNA repair enzymes to restore genomic
integrity. The DNA base-excision repair and DNA double-strand break repair
pathways are particularly important. While single base damages are rapidly
excised and repaired using the opposite (undamaged) strand as a template, the
correct repair of DNA double-strand breaks may present more difficulties to
cellular enzymes owing to the loss of template. In the last few years evidence in
support of several enzymatic pathways for the repair of such double-stranded
damage has been found. At present we may distinguish at least three pathways:
homologous recombination repair, non-homologous (DNA-PK-dependent) end joining,
and repeat-driven end joining. This paper focuses on evidence for the first and
third of these pathways, and considers in particular their relative importance in
mammalian cells and implications for the fidelity of repair.
PMID- 10196660
TI - Double strand break rejoining by the Ku-dependent mechanism of non-homologous end
joining.
AB - The DNA-dependent protein kinase functions in the repair of DNA double strand
breaks (DSBs) and in V(D)J recombination. To gain insight into the function of
DNA-PK in this process we have carried out a mutation analysis of Ku80 and DNA
PKcs. Mutations at multiple sites within the N-terminal two thirds of Ku80 result
in loss of Ku70/80 interaction, loss of DNA end-binding activity and inability to
complement Ku80 defective cell lines. In contrast, mutations in the carboxy
terminal region of the protein do not impair DNA end-binding activity but
decrease the ability of Ku to activate DNA-PK. To gain insight into important
functional domains within DNA-PKcs, we have analysed defective mutants, including
the mouse scid cell line, and the rodent mutants, irs-20 and V-3. Mutational
changes in the carboxy terminal region have been identified in all cases. Our
results strongly suggest that the C-terminus of DNA-PKcs is required for kinase
activity.
PMID- 10196662
TI - Radiation-induced signal transduction. Mechanisms and consequences.
AB - Over a dose range up to 50 Gy of low-LET (linear energy transfer) ionizing
radiation and up to 5 kJ/m2 UVB, mammalian cells convert molecular damage into
productive response (mostly gain of function). By inactivation of negative
regulatory components, such as protein tyrosine phosphatases as one mechanism
discovered, the balance between restraining and stimulating influences is
disturbed and an increase in signal flow results. Also DNA damage causing
transcriptional arrest produces a signalling cascade of as yet unknown details.
Such stimulation of the intracellular communication network can lead to
apoptosis, elevated cell cycling and differentiation processes possibly including
repair and recombination. The outcome likely depends on integration of all
signals received which is as yet ill-understood. Although accurate determinations
of low-dose inductions have not been achieved for technical reasons, the dose
response curves of induced signal transduction likely show threshold
characteristics, in contrast to the direct consequences of DNA damage.
PMID- 10196661
TI - Cellular response to DNA damage. Link between p53 and DNA-PK.
AB - Cells which lack DNA-activated protein kinase (DNA-PK) are very susceptible to
ionizing radiation and display an inability to repair double strand DNA breaks.
DNA-PK is a member of a protein kinase family that includes ATR and ATM which
have strong homology in their carboxy-terminal kinase domain with PL-3 kinase.
ATM has been proposed to act upstream of p53 in cellular response to ionizing
radiation. DNA-PK may similarly interact with p53 in cellular growth control and
in mediation of the response to ionizing radiation.
PMID- 10196663
TI - Induction of genetic instability by ionizing radiation.
AB - Evidence is presented to support the hypothesis that radiation may induce a
heritable, genome-wide process of instability that leads to an enhanced frequency
of genetic changes occurring among the progeny of the original irradiated cell.
This instability is transmissible over many generations of cell replication.
Mutational instability is induced in a relatively large fraction (approximately
10%) of the cell population, and may be modulated by factors acting in vivo.
Thus, it cannot be a targeted event involving a specific gene or set of genes.
There is no dose-response relationship in the range 2-12 Gy, suggesting that the
instability phenotype may be induced by quite low radiation doses. The molecular
mechanisms associated with the genesis of mutations in unstable populations
differ from those for direct X-ray-induced mutations. These results suggest that
it may not be possible to predict the nature of the dose-response relationship
for the ultimate genetic effects of radiation based on a qualitative or
quantitative analysis of the original DNA lesions.
PMID- 10196664
TI - The role of animal models in the development of knowledge of radiation
carcinogenesis and their potential contribution to judgements of risk at low
doses.
PMID- 10196665
TI - DNA repair pathways and dose responses to ionizing radiations.
PMID- 10196666
TI - Mechanisms of mutagenesis in mammalian cells. Application to human thyroid
tumours.
AB - Mutations are defined as stable and irreversible modifications of the normal
genetic message due to small changes in the number or type of bases, or to large
modifications of the genome such as deletions, insertions or chromosome
rearrangements. These lesions are due to either polymerase errors during normal
DNA replication or unrepaired DNA lesions, which will give rise to mutations
through a mutagenic pathway. The molecular process leading to mutagenesis depends
largely on the type of DNA lesions. Base modifications, such as 8-oxo-guanine or
thymine glycol, both induced by ionizing radiations (IR), are readily replicated
leading to direct mutations, usually base-pair substitutions. The 8-oxo-G gives
rise predominantly to G to T transversions, the type of mutations found in ras or
p53 gene from IR-induced tumors. Bulky adducts produced by chemical carcinogens
or UV-irradiation are usually repaired by the nucleotide excision repair (NER)
pathway which is able to detect structural distortion in the normal double-strand
DNA backbone. These lesions represent a blockage to DNA and RNA polymerases as
well as some signal for p53 accumulation in the damaged cell. In the absence of
repair, these lesions could be eventually replicated owing to the induction of
specific proteins at least in bacteria during the SOS process. The precise nature
of the error-prone replication across an unexcised DNA lesion in the template is
not fully understood in detailed biochemical terms, in mammalian cells. IR
basically produce a very large number of DNA lesions from unique base
modifications to single- or double-strand breaks and even complex DNA lesions due
to the passage of very high energy particles or to a local re-emission of
numerous radicals. The breakage of the double-helix is a difficult lesion to
repair. Either it will result in cell death or, after an incorrect
recombinational pathway, it will induce frameshifts, large deletions or
chromosomal rearrangements. Most of the IR-induced mutations are recessive ones,
requiring therefore a second genetic event in order to exhibit any harmful effect
and a long latency period before the development of a radiation-induced tumor.
The fact that IR essentially induced deletions and chromosomal translocations
renders very difficult the use of the p53 gene as a marker for mutation analysis.
In agreement with the type of lesions induced by IR, it is interesting to point
out that the presence has been observed, in a vast majority of radiation-induced
papillary thyroid carcinomas (PTC), of an activated ret proto-oncogene originated
by the fusion of the tyrosine kinase 3' domain of this gene with the 5' domain of
four different genes. These ret chimeric genes which are due to intra- or inter
chromosomal translocations, were called RET/PTC1 to PTC5. The RET/PTC
rearrangements were found in PTC from children contaminated by the Chernobyl fall
out as well as in tumours from patients with a history of therapeutic external
radiation, with a frequency of 60-84%. This frequency was only 15% in
'spontaneous' PTC. The type of ret chimeric gene predominantly originated by the
accidental or therapeutic IR was different. Indeed, PTC1 was present in 75% of
the tumours linked to a therapeutic radiation and PTC3 in 75% of the Chernobyl
ones. The other forms of RET/PTC were observed in only a minority of the post
Chernobyl PTC (< 20%). The difference in the frequency of PTC1 and PTC3 in both
types of PTC, is statistically significant (P < 10(-5), Fischer's exact test). In
two of the post-therapeutic radiation PTC, RET/PTC1 and PTC3 were simultaneously
present. A PTC1 gene was also observed in 45% of the adenomas appearing after
therapeutic radiation. The long-period of latency between exposure to IR and the
appearance of thyroid tumours is probably due to the conversion of a heterozygote
genotype of IR-induced mutations to a homozygote one. It will be interesting to
use this time lag in accidental or therapeutic-irradiated p
PMID- 10196667
TI - Role of connexin (gap junction) genes in cell growth control and carcinogenesis.
AB - Gap junctional intercellular communication (GJIC) is considered to play a key
role in the maintenance of tissue independence and homeostasis in multicellular
organisms by controlling the growth of GJIC-connected cells. Gap junction
channels are composed of connexin molecules and, so far, more than a dozen
different connexin genes have been shown to be expressed in mammals. Reflecting
the importance of GJIC in various physiological functions, deletion of different
connexin genes from mice results in various disorders, including cancers, heart
malformation or conduction abnormality, cataract, etc. The possible involvement
of aberrant GJIC in abnormal cell growth and carcinogenesis has long been
postulated and recent studies in our own and other laboratories have confirmed
that expression and function of connexin genes play an important role in cell
growth control. Thus, almost all malignant cells show altered homologous and/or
heterologous GJIC and are often associated with aberrant expression or
localization of connexins. Aberrant localization of connexins in some tumour
cells is associated with lack of function of cell adhesion molecules, suggesting
the importance of cell-cell recognition for GJIC. Transfection of connexin genes
into tumorigenic cells restores normal cell growth, supporting the idea that
connexins form a family of tumour-suppressor genes. Some studies also show that
specific connexins may be necessary to control growth of specific cell types. We
have produced various dominant-negative mutants of Cx26, Cx32 and Cx43 and showed
that some of them prevent the growth control exerted by the corresponding wild
type genes. However, we have found that connexins 32, 37 and 43 genes are rarely
mutated in tumours. In some of these studies, we noted that connexin expression
per se, rather than GJIC level, is more closely related to growth control,
suggesting that connexins may have a GJIC-independent function. We have recently
created a transgenic mouse strain in which a mutant Cx32 is specifically
overexpressed in the liver. Studies with such mice indicate that Cx32 plays a key
role in liver regeneration after partial hepatectomy. A decade ago, we proposed a
method to enhance killing of cancer cells by diffusion of therapeutic agents
through GJIC. Recently, we and others have shown that GJIC is responsible for the
bystander effect seen in HSV-tk/ganciclovir gene therapy. Thus, connexin genes
can exert dual effects in tumour control: tumour suppression and a bystander
effect for cancer therapy.
PMID- 10196668
TI - Hybrid polar inducers of transformed cell differentiation/apoptosis. From the
cell to the clinic.
PMID- 10196669
TI - Adaptive response and induced resistance.
AB - Cellular stress responses are upregulated following exposure to radiation and
other DNA-damaging agents. Therefore radiation response can be dose dependent so
that small acute exposures (and possibly exposures at very low dose rates?) are
more lethal per unit dose than larger exposures above a threshold (typically 10
40 cGy) where induced radioprotection is triggered. We have termed these
interlinked phenomena low-dose hypersensitivity (HRS) and induced radioresistance
(IRR) as the dose increases. HRS/IRR has been recorded in cell-survival studies
with yeast, bacteria, protozoa, algae, higher plant cells, insect cells,
mammalian and human cells in vitro, and in studies on animal normal-tissue models
in vivo. There is indirect evidence that cell survival-related HRS/IRR in
response to single doses is a manifestation of the same underlying mechanism that
determines the well-known adaptive response in the two-dose case and that it can
be triggered by high- and low-LET radiations as well as a variety of other stress
inducing agents such as hydrogen peroxide and chemotherapeutic agents. Little is
currently known about the precise nature of this underlying mechanism, but there
is evidence that it operates by increasing the amount and rate of DNA repair,
rather than by indirect mechanisms such as modulation of cell-cycle progression
or apoptosis. Changed expression of some genes, only in response to low and not
high doses, may occur within a few hours of irradiation and this would be rapid
enough to explain the phenomenon of induced radioresistance although its specific
molecular components have yet to be identified. Net cancer risk is a balance
between cell transformation and cell kill. Our known low-dose cell-survival
responses suggest that lethality may more than compensate for transformation at
low radiation doses. However, adaptive reduction in sensitivity to radio-mutation
has also been reported, which implies the existence also of enhanced mutation
following very low single doses. So far this has not been confirmed, but provided
the trigger dose for mutational protection was lower than the trigger dose for
protection against cytotoxicity, cell killing would still dominate over at least
the first 10 cGy of low-LET exposure. This would lead to a non-linear, threshold,
dose-risk relationship and even provide some explanation for anecdotal reports of
apparent 'health promoting' effects and lowered cancer risk from very low
exposure to ionising radiation.
PMID- 10196670
TI - The various models of carcinogenesis. Susceptibility genes, mutations, epigenetic
processes.
PMID- 10196671
TI - Mechanisms, dose-effect relationship. Recent data.
PMID- 10196672
TI - Time sequence of cancer occurrence. Implications in low level radiation risk
assessment.
AB - A total of 8,229 C57 Black mice of both sexes were randomly assigned to various
groups. In some groups, mice aged 33 +/- 3 days were submitted to either sham,
neutron or cobalt external radiation at 32, 45, 63, 88 and 123 mGy or at 18, 25,
36 and 51 cGy dose levels, respectively. In other groups, mice either at birth or
weaning, were injected with tritiated thymidine or tritiated water, or were given
tritiated water as drinking water for the entire lifespan. The main purpose of
the experiment was to investigate the low dose-response relationship of cancer
induction, especially leukemogenesis and to evaluate the excess risk, using
actuarial age-specific rates. Following neutron or cobalt exposure, the
phenotypic occurrence of lymphocytic lymphomas was earlier in appearance and
higher in yield during the first decades of lifespan in irradiated groups versus
matching controls, whereas such occurrence was markedly lower in yield at a later
age. Under parallel experimental conditions, induction of reticulum cell
lymphomas, however, was uniformly enhanced throughout the entire lifespan.
Induction rates of all tumors (reticular and solid) pooled were significantly
increased, and more so following cobalt than neutron irradiation. In mice
injected with tritiated thymidine, the overall tumor incidence was increased
monotonically throughout the lifespan. In mice exposed to tritiated water, the
incidence of lymphocytic lymphomas was markedly increased throughout the
lifespan, whereas no such effect was observed for reticulum cell tumors. In the
light of tumor data analysis, it appears that selection of a particular type of
tumor as a dependent variable for dose-response assessment cannot disregard the
primary modulation of the whole tumor spectrum, In C57 Black murine
leukemogenesis, the shape and structure of the dose-response regression curve
over the entire lifespan dose not fit the linear-quadratic model. It is, however,
theorized that our data are consistent with the two-mutation clonal expansion
model, assuming creation of initiated cells which are added to the pool of
spontaneously occurring initiated cells and implying that the excess risk is
initially high at early age and then decreases with increasing age following
exposure. It is concluded that murine radiocarcinogenesis investigation may
contribute to improving the assessment as well as understanding the underlying
mechanisms of low level radiation hazards.
PMID- 10196673
TI - Molecular biology, epidemiology, and the demise of the linear no-threshold (LNT)
hypothesis.
AB - The prime concern of radiation protection policy since 1959 has been protecting
DNA from damage. The 1995 NCRP Report 121 on collective dose states that since no
human data provides direct support for the linear no threshold hypothesis (LNT),
and some studies provide quantitative data that, with statistical significance,
contradict LNT, ultimately, confidence in LNT is based on the biophysical concept
that the passage of a single charged particle could cause damage to DNA that
would result in cancer. Current understanding of the basic molecular biologic
mechanisms involved and recent data are examined before presenting several
statistically significant epidemiologic studies that contradict the LNT
hypothesis. Over eons of time a complex biosystem evolved to control the DNA
alterations (oxidative adducts) produced by about 10(10) free radicals/cell/d
derived from 2-3% of all metabolized oxygen. Antioxidant prevention, enzymatic
repair of DNA damage, and removal of persistent DNA alterations by apoptosis,
differentiation, necrosis, and the immune system, sequentially reduce DNA damage
from about 10(6) DNA alterations/cell/d to about 1 mutation/cell/d. These
mutations accumulate in stem cells during a lifetime with progressive DNA damage
control impairment associated with aging and malignant growth. A comparatively
negligible number of mutations, an average of about 10(-7) mutations/cell/d, is
produced by low LET radiation background of 0.1 cGy/y. The remarkable efficiency
of this biosystem is increased by the adaptive responses to low-dose ionizing
radiation. Each of the sequential functions that prevent, repair, and remove DNA
damage are adaptively stimulated by low-dose ionizing radiation in contrast to
their impairment by high-dose radiation. The biologic effect of radiation is not
determined by the number of mutations it creates, but by its effect on the
biosystem that controls the relentless enormous burden of oxidative DNA damage.
At low doses, radiation stimulates this biosystem with consequent significant
decrease of metabolic mutations. Low-dose stimulation of the immune system may
not only prevent cancer by increasing removal of premalignant or malignant cells
with persistent DNA damage, but used in human radioimmunotherapy may also
completely remove malignant tumors with metastases. The reduction of gene
mutations in response to low-dose radiation provides a biological explanation of
the statistically significant observations of mortality and cancer mortality risk
decrements, and contradicts the biophysical concept of the basic mechanisms upon
which, ultimately, the NCRPs confidence in the LNT hypothesis is based.
PMID- 10196674
TI - Irradiation and second cancers. The thyroid as a case in point.
AB - The thyroid gland is highly sensitive to radiation during childhood: the risk of
thyroid tumours is increased for mean doses as low as 100 mGy and for higher
doses, the risk increases linearly with the dose. Excess relative risk is
important, being 7.7 for 1 Gy delivered to the thyroid gland during childhood.
The risk of thyroid tumours is modified by several factors: a) age at exposure:
in childhood, the risk decreases with increasing age at exposure and is not
significant after 20 years; b) gender: females are two times more likely than
males to develop thyroid tumours; c) genetic predisposition due to a defect in
DNA repair mechanisms, and dietary and hormonal factors may modify the risk; d)
the influence of fractionation and dose rate is not well established. Radioiodine
131 (1311) used for medical purposes has almost no tumourigenic effect on the
adult thyroid gland. The consequences of the Chernobyl accident have clearly
shown that the risk of thyroid cancer after exposure to 1311 in childhood is
important, and that such exposure should be prevented by potassium iodine
prophylaxis. RET/PTC rearrangements are found in 60-80% of papillary carcinomas
and in 45% of adenomas occurring after radiation exposure. They are found in 5
15% of papillary carcinoma and in no follicular adenomas that occurred in the
absence of radiation exposure.
PMID- 10196675
TI - Contribution of human data to the analysis of human carcinogenesis.
AB - Human data strongly suggest that small doses or low concentrations of genotoxic
agents cause only a relatively small number of human cancers. They emphasize the
role of promotion, in particular that associated with cell proliferation. There
is therefore a qualitative difference between high doses of genotoxic agents
which provoke cell death and a compensatory increase in cell division, and low
doses which do not. During the promotion phase, human data demonstrate the
importance of induced genetic instability and defects in apoptosis as well as
that of cell immortalization which play a main role for the accumulation in a
cell genome of several specific lesions. Carcinogenesis is a complex process in
which initial mutations do not appear to be a limiting or crucial step. This view
is supported by the paramount influence of age on the induction by radiation of
thyroid and breast cancer. It is also compatible with practical thresholds
observed in subjects whose bones or liver were exposed to alpha-emitters, as well
as with the curvilinearity in the leukemia incidence dose-response in the
Japanese atomic bomb survivors. The linear no threshold model assumes that: 1)
the probability of DNA lesion repair is constant whatever the dose and, hence,
the number of lesions provoked in the same cell and the surrounding cells; 2) the
probability for a damaged cell to evolve toward an invasive cancer is not
influenced by the possible promotional effect of further irradiation or induced
tissue proliferation, nor the control exerted by surrounding cells. These
assumptions deserve a critical analysis.
PMID- 10196676
TI - Radiation-inducible gene therapy.
AB - The radiation-inducible chimeric genetic construct Egr-TNF alpha introduced into
human xenografts produces cytotoxicity of infected tumor cells resulting in tumor
growth inhibition. The interaction between Egr-TNF and radiation is selectively
cytotoxic for the tumor microvasculature resulting in vascular thrombosis and
tumor necrosis. Gene therapy combined with radiation therapy offers great
potential for the treatment of localized human cancers.
PMID- 10196677
TI - The effects of neutrons in Hiroshima. Implications for the risk estimates.
AB - Risk estimates for radiation-induced late effects are relevant to various
considerations in radiation protection. Most of these considerations relate to
small doses for which no excess risk can be seen even in extensive
epidemiological studies. Risk coefficients for radiation protection must,
therefore, be based on uncertain extrapolation of observations obtained at
moderate or high doses. The extrapolation can not be replaced, as yet, by new,
more direct information on processes such as radiation-induced genetic
instability or adaptive response. While the new findings indicate complexities
that may be highly relevant to the effectiveness- or lack of effectiveness- of
radiation at low doses, they remain insufficiently understood to permit a
decision as to whether dose-effect relations are linear, curvilinear, or have a
threshold in dose. In view of these uncertainties radiation-protection
regulations are, today, based on the conservative assumption of a linear dose
dependence without threshold. This approach assures a sufficient degree of
protection, but it may become unreasonably over-conservative, when the cautious
hypothesis is treated as proven fact, and when-in addition-the assumed initial
slope of the dose relation is not critically evaluated. A reliable evaluation
needs to be based on the follow-up of the atom-bomb bomb survivors, and several
major aspects of current interest are discussed here. a) Mortality from solid
tumours in Hiroshima shows a statistically significant excess at a colon dose of
50 mGy; however, it is likely that this is the result of a bias in assigning
causes of death. b) The solid cancer mortality data of the atom-bomb survivors
are consistent with linearity in dose, but they can be shown to be equally
consistent with a considerable degree of curvature. c) Even with the present
dosimetry system, DS86, a substantial part of the effect at small doses in
Hiroshima could be due to neutrons. If this is the case, the risk estimates for
gamma-rays need to be accordingly decreased. d) Numerous neutron-activation
measurements in Hiroshima indicate that the DS86 underestimates the neutron
doses. The evidence is, up to now, based only on activation products of low
energy neutrons, but efforts are currently underway to determine activation
products of high energy neutrons. If these measurements should substantiate the
present trend, the cancer data in Hiroshima would cease to be reliable proof of
an effect of gamma-rays at low doses. Instead the dose dependence for gamma-rays
could be purely quadratic, and any initial slope in the linear-quadratic
dependence might well be attributable to neutrons only.
PMID- 10196678
TI - How to collect pertinent data for the assessment of the medical consequences of
an irradiation?
PMID- 10196679
TI - Regulation of low-level radiation.
PMID- 10196680
TI - Cellular signal adaptation with damage control at low doses versus the
predominance of DNA damage at high doses.
AB - Ionizing radiation is known to potentially interfere with cellular functions at
all levels of cell organization and induces DNA lesions apparently with an
incidence linearly related to D, also at low doses. On the other hand, low doses
have also been observed to initiate a slowly appearing temporary protection
against causation and accumulation of DNA lesions, involving the radical
detoxification system, DNA repair and removal of DNA damage. This protection
apparently does not operate at high doses; it has been described to be nonlinear,
increasing initially with D, beginning to decrease when D exceeds approximately
0.1-0.2 Gy, and eventually disappearing at higher D. The various adaptive
responses have been shown to last individually from hours to weeks in different
cell types and resemble responses to oxidative stress. Damage to DNA is
continuously and endogenously produced mainly by reactive oxygen species (ROS)
generated in a normal oxidative metabolism. This endogenous DNA damage
quantitatively exceeds DNA damage from low-dose irradiation, by several orders of
magnitude. Thus, the protective responses following acute low-dose irradiation
may be presumed to mainly counteract the endogenous DNA damage. Accordingly, the
model described here uses two dose-effect functions, a linear one for causing and
a nonlinear one for protecting against DNA damage from whatever cause in the
irradiated cells and tissues. The resulting net dose-risk function strongly
suggests that the incidence of cancer versus dose in the irradiated tissues is
much less likely to be linear than to exhibit a threshold. The observed cancer
incidence may even fall below the spontaneous incidence, when D to cells is below
approximately 0.2 Gy. However incomplete, these data support a reexamination of
the LNT hypothesis.
PMID- 10196681
TI - Effect of leisure time and working activity on principal risk factors and
relative interactions in active middle-aged men.
AB - DESIGN: This study was designed to evaluate, in a cohort of 1039 middle-aged men,
the interaction between the duration and intensity of physical activity performed
either during leisure time (competitive sports, walking, cycling) or work, and
principal coronary disease risk factors. METHOD: A cohort of subjects aged 45-64
years were recruited in 1993. Subjects included both individuals who were
physically active and those who were sedentary, and were age-matched. RESULTS:
Leisure time physical activity was inversely related to levels of total
cholesterol, triglycerides, and fibrinogen, and to diastolic and systolic blood
pressure. High-density lipoprotein cholesterol level was directly related to
leisure time activity. Working activity, even if strenuous, was not related to
risk profile. Leisure time activity did not favorably influence lipid levels in
smokers, obese subjects or those with known dyslipidemia. CONCLUSIONS: This study
further reinforces the use of continuous diet and drug treatment in dyslipidemic
subjects and in smokers, who have to refrain from smoking if they are to benefit
fully from the effects of physical activity.
PMID- 10196682
TI - Granulomatous 'foreign body reactions' contribute to exaggerated in-stent
restenosis.
AB - BACKGROUND: Results of previous studies with stents coated with 'biocompatible'
polymers showed that severe inflammatory reaction and subsequent in-stent
restenosis may occur. OBJECTIVE: To evaluate the contribution of granulomatous
reaction from uncoated stents to formation of in-stent neointimal hyperplasia.
METHODS: Uncoated stainless-steel stents were implanted into 21 porcine coronary
arteries without oversizing and harvested after 2 months (n = 6) or 6 months (n =
7). We compared the stents with granulomatous reaction with those without foreign
body reaction. RESULTS: Granulomatous reactions occurred in five 21 stents and
resulted in there being significantly greater in-stent neointimal hyperplasia
than there was with stents without foreign-body reaction (angiographic diameter
stenosis 45 +/- 36 versus 16 +/- 16%, area of neointimal 3.30 +/- 1.4 versus 1.22
+/- 0.4 mm2, thickness of neointima 0.46 +/- 0.29 versus 0.11 +/- 0.09 mm,
stenosed area 56 +/- 24 versus 20 +/- 7%, P < 0.01 for each comparison). This
increase in amount of neointima was accompanied by significantly greater
proliferating cell nuclear antibody staining (15 +/- 5 versus 3 +/- 2%, P < 0.05)
in the presence of a granuloma near the stent struts. CONCLUSIONS: A localized
granulomatous reaction is associated with a significant increase in amount of
stent neointima and proliferation of cells. Thus, permanent stent implants may
provoke granulomatous vascular reactions that may affect late-healing responses
and clinical outcomes.
PMID- 10196683
TI - Critical appraisal of exercise variables: a treadmill study.
AB - BACKGROUND: New criteria for diagnosing ischemic response to treadmill exercise
testing (TET) have continuously been proposed. Simultaneous comparison of test
performances according to these criteria is likely contributory to interpreting
TET and needs to be updated time after time. This study was conducted to
accomplish this end. METHODS: A comparison of test performances of various TET
variables for a cohort of 107 clinical normals and 139 angiographic patients with
normal resting electrocardiograms was performed. Angiographic references included
enumeration of diseased coronary vessels, Gensini's and Duke's coronary scores,
left ventricular wall motion score and ejection fraction at rest. RESULTS: The ST
segment-related variables (depression, integral, and heart-rate-adjusted slope or
index) outdid non-ST-segment variables (changes in R amplitude, the Athens QRS
score, peak exercise blood pressure increment and recovery pressure ratios; most
P < 0.05) in diagnosing coronary artery disease. Among them the heart-rate
adjusted ST-segment depression performed still better. This trend was not evident
in identifying left main and three-vessel disease. However, correlation to the
coronary scores favored the ST-segment-related criteria (r = 0.18-0.39, P < 0.05
to P < 0.001 versus r = 0.05-0.23, NS to P < 0.01) for evaluating severity of
coronary artery disease. CONCLUSIONS: For patients with normal resting
electrocardiograms, the adjustment of ST-segment depression for heart rate is
valuable for evaluating coronary artery disease.
PMID- 10196684
TI - Type 2 diabetes: one disease, multiple cardiovascular risk factors.
AB - Type 2 diabetes mellitus is a major independent risk factor for coronary artery
disease. Atherosclerosis accounts for about 80% of all deaths from type 2
diabetes, of which roughly 75% are attributable to coronary artery disease and
the remainder to cerebrovascular or peripheral vascular events [1]. The earlier
onset and accelerated course of atherosclerosis in individuals with type 2
diabetes mellitus is multifactorial. Type 2 diabetes is associated with
abnormalities in lipoprotein metabolism and increased propensity for oxidative
damage. The hyperglycemia of patients with type 2 diabetes, in itself, may
accelerate vascular damage. Type 2 diabetes is a hypercoagulable state
attributable to enhanced coagulation and decreased fibrinolysis, as well as
platelet hyperaggregability and endothelial dysfunction. Hypertension is common
in individuals with type 2 diabetes and has a major impact in the accelerated
atherosclerosis of this disease. This review provides an overview of selected
aspects of these alterations.
PMID- 10196685
TI - Exercise and physical therapy in elderly, more severely incapacitated patients in
cardiac rehabilitation.
PMID- 10196686
TI - The physiology of physical performance and training in old age.
AB - Maximal aerobic power, muscular strength and explosive power decline even with
healthy ageing. Their values are lower in women than in men of the same age.
Women are therefore at risk of crossing functionally important thresholds much
earlier. Physical training can increase maximal aerobic power, muscular strength
and explosive power in older men and women. These increases may help to delay the
crossing of thresholds, and may therefore help the older individual to maintain
their independence. For the older patient there may be an additive effect of age
and disease. Rehabilitation-induced improvements in exercise performance can
therefore offer the potential for even greater gains in the everyday functional
ability of the older cardiac patient. When performing tests of physiological
responses to exercise or when designing exercise programmes for older people,
adaptations need to be made to ensure they are suitable for use with the intended
age group.
PMID- 10196687
TI - Are current exercise test protocols appropriate for older patients?
PMID- 10196688
TI - Psychosocial issues for cardiac rehabilitation with older individuals.
AB - Psychological management of older people undergoing cardiac rehabilitation should
be delivered, in the main, as it is to younger people with the heterogeneity of
patient characteristics taken as standard. General considerations in delivering a
service to older people include societal definitions of ageing, the profile of
older cardiac patient groups, ageism as practised by both health professionals
and patients, psychological issues of particular relevance to ageing and evidence
from scientific studies with older individuals. These topics are considered in
this review. The challenge is to develop a system which includes and is
responsive to this growing subgroup of patients who can benefit from cardiac
rehabilitation.
PMID- 10196689
TI - Cost implications of cardiac rehabilitation in older patients.
PMID- 10196690
TI - Bibliography current world literature.
PMID- 10196691
TI - Multipoint genomic scanning for quantitative loci: effects of map density,
sibship size and computational approach.
AB - Multipoint interval mapping (MIM) and the MAPMAKER/SIBS program (M/S) are two
methods of mapping quantitative loci by examining identity by descent (IBD)
sharing in a region spanned by multiple microsatellite DNA markers. For the
purpose of comparison, we simulated a quantitative trait controlled by a two
locus model, and evaluated the power and genome-wide false positive rate of both
approaches. Based on our simulation, we examined the effects of marker density (5
cM, 10 cM and 20 cM) and sibship size (2, 3, 4 and 5) on the power to detect
linkage. Our results indicate that a 10 cM map provides the optimal trade-off
between power and type I error, and that the power of MIM increases with sibship
size and, in general, performs better than MAPMAKER/SIBS. Furthermore, we
conclude that using a reasonable sample of randomly ascertained sibships, it is
possible to map a quantitative trait locus (QTL) which accounts for 25% of the
phenotypic variance.
PMID- 10196692
TI - Association and linkage analysis of candidate chromosomal regions in multiple
sclerosis: indication of disease genes in 12q23 and 7ptr-15.
AB - Four recent genome-wide screen studies in multiple sclerosis (MS) identified a
number of candidate regions for susceptibility genes in addition to the HLA
complex in 6p21. However, none of these regions provided formally significant
evidence for genome-wide linkage. We have investigated such regions in 46 Swedish
multiplex MS families, 28 singleton families, 190 sporadic MS patients and 148
normal controls by parametric and nonparametric linkage and association analysis.
One microsatellite marker, in 12q23, provided evidence for association in
addition to suggestive transmission distortion and slightly positive linkage. In
addition, a marker in 7ptr-15 showed a significant transmission distortion as
well as a highly significant score in affected pedigree member analysis, but not
quite significant deviations in association analysis. One of three markers in 5p,
a region implicated in all four previous studies, showed a weakly positive lod
score, but no other evidence of importance. Markers in 2p23, 5q11-13, 6q25, 7q21
22, 11q21-23, 13q33-34, 16p13.2, 18p11.32-23, Xp21.3 provided little or no
evidence of importance for MS. In summary, these data support the importance of
genome-wide screens in the identification of new candidate loci in polygenic
disorders.
PMID- 10196693
TI - Testing of human homologues of murine obesity genes as candidate regions in
Finnish obese sib pairs.
AB - The human homologues of recently discovered murine obesity genes provide relevant
candidates to study the genetic component of obesity in humans. We analysed the
human counterparts to murine obesity genes ob, db, agouti, tub, melanocortin 4
receptor (MC4-R) and mitochondrial uncoupling proteins 2 and 3 (UCP2 and UCP3),
as well as two other chromosomal regions reported to be linked to obesity-related
phenotypes in restricted populations. We found no significant evidence for
linkage to any analysed loci in our total study material of 105 affected sib
pairs collected from the genetically homogenous population of Finland. However,
several markers on 14 cM chromosomal region flanking the MC4-R gene showed
sharing of alleles identical-by-descent (IBD) more frequently than expected. A
selected subset of non-diabetic obese sib pairs strengthened the P values down to
0.003 in this particular region. The smallest P value (P = 0.001) was obtained
with a marker D18S487 in a subgroup containing only sib pairs with one lean and
one obese parent. We therefore screened seven obese subjects included in our sib
pair material for sequence changes in their MC4-R gene, but no mutations of
apparent causal relationship were found. In conclusion, we could not find
evidence for significant contribution of the chromosomal loci corresponding to
the murine single gene obesity genes for human morbid obesity, but additional
studies are still needed to clarify whether DNA alterations within or adjacent to
the MC4-R gene play some role.
PMID- 10196695
TI - Phenotype-genotype correlation in 20 deletion and 20 non-deletion Angelman
syndrome patients.
AB - Angelman syndrome (AS) is a neurodevelopmental disorder caused by the absence of
a maternal contribution to chromosome 15q11-q13. There are four classes of AS
according to molecular or cytogenetic status: maternal microdeletion of 15q11-q13
(approximately 70% of AS patients); uniparental disomy (UPD); defects in a
putative imprinting centre (IM); the fourth includes 20-30% of AS individuals
with biparental inheritance and a normal pattern of allelic methylation in 15q11
q13. Mutations of UBE3A have recently been identified as causing AS in the latter
group. Few studies have investigated the phenotypic differences between these
classes. We compared 20 non-deletion to 20 age-matched deletion patients and
found significant phenotypic differences between the two groups. The more severe
phenotype in the deletion group may suggest a contiguous gene syndrome.
PMID- 10196694
TI - An Asn > Lys substitution in saposin B involving a conserved amino acidic residue
and leading to the loss of the single N-glycosylation site in a patient with
metachromatic leukodystrophy and normal arylsulphatase A activity.
AB - Sphingolipid activator proteins are small glycoproteins required for the
degradation of sphingolipids by specific lysosomal hydrolases. Four of them,
called saposins, are encoded by the prosaposin gene, the product of which is
proteolytically cleaved into the four mature saposin proteins (saposins A, B, C,
D). One of these, saposin B, is necessary in the hydrolysis of sulphatide by
arylsulphatase A where it presents the solubilised substrate to the enzyme. As an
alternative to arylsulphatase A deficiency, deficiency of saposin B causes
metachromatic leukodystrophy. We identified a previously undescribed mutation
(N215K) in the prosaposin gene of a patient with metachromatic leukodystrophy but
with normal arylsulphatase A activity and elevated sulphatide in urine. The
mutation involves a highly conserved amino acidic residue and abolishes the only
N-glycosylation site of saposin B.
PMID- 10196696
TI - Analysis of the trinucleotide CAG repeat from the human mitochondrial DNA
polymerase gene in healthy and diseased individuals.
AB - The human nuclear gene (POLG) for the catalytic subunit of mitochondrial DNA
polymerase (DNA polymerase gamma) contains a trinucleotide CAG microsatellite
repeat within the coding sequence. We have investigated the frequency of
different repeat-length alleles in populations of diseased and healthy
individuals. The predominant allele of 10 CAG repeats was found at a very similar
frequency (approximately 88%) in both Finnish and ethnically mixed population
samples, with homozygosity close to the equilibrium prediction. Other alleles of
between 5 and 13 repeat units were detected, but no larger, expanded alleles were
found. A series of 51 British myotonic dystrophy patients showed no significant
variation from controls, indicating an absence of generalised CAG repeat
instability. Patients with a variety of molecular lesions in mtDNA, including
sporadic, clonal deletions, maternally inherited point mutations, autosomally
transmitted mtDNA depletion and autosomal dominant multiple deletions showed no
differences in POLG trinucleotide repeat-length distribution from controls. These
findings rule out POLG repeat expansion as a common pathogenic mechanism in
disorders characterised by mitochondrial genome instability.
PMID- 10196698
TI - Characterisation and expression of a large, 13.7 kb FMR2 isoform.
AB - FMR2 is the gene associated with FRAXE fragile site non-specific mental
retardation (FRAXE MRX). Previously a male patient was identified with
developmental delay and speech problems who had a deletion within intron 3 of
FMR2. No known FMR2 exonic sequences were missing in this patient. Detailed
northern blot analysis revealed existence of a new large isoform of FRM2 in
foetal brain. This isoform was characterised and found to be due entirely to an
addition of an extra 4.9 kb of the 3' UTR to the previously characterised 8.755
kb FMR2 transcript. This excluded involvement of the large FMR2 isoform in the
MRX phenotype of three individuals now known to have the same deletion of intron
3 FMR2 sequences. Expression studies on the new 13.7 kb FMR2 isoform show that it
is expressed predominantly in foetal brain and adult pituitary gland, whilst the
expression of the shorter previously characterised 8.755 kb isoform is broader,
including testis, thymus and placenta. Possible consequences of the alternative
processing and expression of FMR2 for the molecular pathology of FRAXE MRX are
discussed.
PMID- 10196697
TI - Study of three intragenic polymorphisms in the Machado-Joseph disease gene (MJD1)
in relation to genetic instability of the (CAG)n tract.
AB - Intergenerational instability is one of the most important features of the
disease-associated trinucleotide expansions, leading to variation in size of the
repeat among and within families, which manifests as variable age at onset and
severity, and is probably the basis for the occurrence of anticipation. Several
factors are known to affect the degree of instability, namely the type of
repeated sequence, its initial size, the presence or absence of interruptions in
the repetitive tract and the gender of the transmitting parent. A recent study
demonstrated the effect of an intragenic polymorphism (C987GG/G987GG) in the
Machado-Joseph disease causative gene, immediately downstream of the CAG repeat,
on the intergenerational instability of the expanded repeat. Surprisingly, there
was an effect not only of the specific allele in cis to the disease chromosome,
but also of the allele on the normal chromosome, suggesting the existence of an
interaction between the normal and expanded alleles that affects the fidelity of
replication of the (CAG)n tract. This effect could be a direct effect of the
polymorphism studied or, alternatively, this polymorphism could be in
disequilibrium with some other flanking sequence which affects the instability of
the repetitive (CAG)n tract. In order to confirm the previous results in a
different population and to distinguish between a direct and indirect effect of
the CGG/GGG polymorphism, we typed 70 parent-progeny pairs for which the
variation in the (CAG)n length in the MJD1 gene was known, for three intragenic
polymorphisms: C987GG/G987GG and two additional, newly described ones,
TAA1118/TAC1118 and A669TG/G669TG. We also typed a control population of 125
individuals for the A669TG/G669TG, C987GG/G987GG and TAA1118/TAC1118
polymorphisms, in an attempt to identify any association between haplotype and
(CAG)n length in normal chromosomes, suggestive of an instability-predisposing
effect of the repeat-flanking sequences, which could have led to the origin of
the MJD mutation in the human population. We confirmed the effect of the
C987GG/G987GG polymorphism on intergenerational instability when present in
trans. Our results suggest that this effect is restricted to a small region of
the gene, immediately downstream of the CAG repeat, which includes this
particular nucleotide substitution and the stop codon of the MJD1 cDNA, and is
not a more widespread chromosomal effect. The lack of a significant association
of any specific intragenic haplotype with larger CAG repeats in normal
chromosomes, together with the absence of an effect of the intragenic haplotype
in cis on the intergenerational instability of the expanded (CAG)n in MJD
families does not indicate the existence of an instability-predisposing
haplotype.
PMID- 10196699
TI - A complex haemoglobinopathy diagnosis in a family with both beta zero- and alpha
(zero/+)-thalassaemia homozygosity.
AB - The occurrence of point mutation alpha-thalassaemia and of complex combinations
of haemoglobin defects is underestimated. Haemoglobinopathies, the most frequent
monogenic recessive autosomal disorder in man, occur predominantly in
Mediterranean, African and Asiatic populations. However, countries of immigration
with a low incidence in the indigenous population, are now confronted with a
highly heterogeneous array of imported defects. Furthermore, the occurrence of
severe phenotypes is bound to increase in the near future because of the
endogamous growth of the ethnical minorities and the lack of prevention. We
describe an Afghan family in which both partners of a consanguineous relationship
are carriers of a beta- as well as an alpha-thalassaemia determinant. The
combination of defects was revealed by the in vitro measurement of the beta/alpha
biosynthetic ratio and was characterised at the DNA level. The molecular defects
involved are the Cd5(-CT), a Mediterranean beta zero-thalassaemia mutation, and
the alpha 2(zero/+)-thalassaemia AATA(-AA) polyadenylation defect. The alpha
thalassemia defect is a rare RNA-processing mutant described only twice before in
heterozygous form in Asian-Indian patients. The mutation suppresses the
expression of a alpha 2 gene and reduces the expression of the less efficient, 3'
located alpha 1 gene as well, inducing a near alpha zero-thalassaemia phenotype.
This defect is now described for the first time in the homozygous condition in
one of the children who, in addition to being homozygous for the alpha
thalassaemia point mutation, is also a carrier of the beta zero-thalassaemia
defect. A previously described homozygous case of the alpha (zero/+)-thalassaemia
condition, caused by a similar polyadenylation defect, was characterised by a
severe HbH disease. However, the patient described here present at 7 years of age
with severe caries, like his beta-thalassaemia homozygous brother but without
hepatosplenomegaly, haemolysis or severe anaemia. The haematological analysis
revealed 9.5 g/dl Hb; 5.4 x 10(12)/I RBC; 0.33 I/I PCV; 61 fl MCV; 17.6 pg MCH
and 6.2% of HbA2. The biosynthetic ratio beta:alpha was 1.6 and no HbH fraction
was detectable either on electrophoresis or as inclusion bodies. The parents
reported no complications during pregnancy, at birth, or in the neonatal period
in rural Afghanistan. We presume therefore that the counterbalancing effect
induced by the co-existing beta-thalassaemia defect could have modified a
potentially severe perinatal HbH disease into a strongly hypochromic but well
compensated 'alpha zero-like heterozygous' thalassaemia phenotype. The risk of a
severe HbH disease, could have been easily missed in this family which was
referred because of a child affected with beta-thalassaemia major.
PMID- 10196700
TI - Genetic control of lipoprotein(a) concentrations is different in Africans and
Caucasians.
AB - Lipoprotein(a) (Lp(a)) represents a quantitative trait in human plasma associated
with atherothrombotic disease. Large variation in the distribution of Lp(a)
concentrations exists across populations which is at present unexplained. Sib
pair linkage analysis has suggested that the apo(a) gene on chromosome 6q27 is
the major determinant of Lp(a) levels in Caucasians. We have here dissected the
genetic architecture of the Lp(a) trait in Africans (Khoi San, South African
Blacks) and Caucasians (Austrians) by family/sib-pair analysis. Heritability
estimates ranged from h2 = 51% in Blacks, h2 = 61% in Khoi San, to h2 = 71% in
Caucasians. Analysis by a variance components model also demonstrated that the
proportion of the total phenotypic variance explained by genetic factors is
smaller in Africans (65%) than in Caucasians (74%). Importantly the sib-pair
analysis clearly identified the apo(a) gene as the major locus in Caucasians
which explained the total genetic variance. In the African samples the apo(a)
gene accounted for only half the genetic variance. Together with previous results
from population studies our data indicate that genetic control of Lp(a) levels
seems to be distinctly different between Africans and Caucasians. In the former
genetic factors distinct from the apo(a) locus and also non-genetic factors may
play a major role.
PMID- 10196701
TI - Screening for minor changes in the distal part of the human dystrophin gene in
Greek DMD/BMD patients.
AB - The distal part of the human dystrophin gene is characterised by particular
features and seems to play an important functional role. Additionally in recent
years several data have implicated minor mutations in this gene region in some
patients with mental retardation (MR). In order to screen for pathogenic
mutations at the distal part of the human dystrophin gene we have used single
strand conformation analysis of products amplified by polymerase chain reaction
(PCR-SSCA) in 35 unrelated male Greek DMD/BMD patients with no detectable
deletions. Seven patients also had severe mental retardation. Direct sequencing
of samples demonstrating a shift of SSCA mobility revealed six different and
pathogenic minor changes, five in DMD and one in a BMD patient. Four of the
mutations were found in DMD patients with severe MR. Three of these mutations
were localised in exon 66, which presents an interesting similarity with part of
the 3' end of the genome of eastern equine encephalomyelitis virus (EEEV). The
present data from Greek DMD/BMD patients give further information about the
phenotypic effects consequent on mutations in exons at the distal part of the
human dystrophin gene.
PMID- 10196702
TI - Tracing past population migrations: genealogy of steroid 21-hydroxylase (CYP21)
gene mutations in Finland.
AB - The genealogic origin of steroid 21-hydroxylase gene (CYP21) mutations and
associated haplotypes was determined in 74 unrelated Finnish families with CYP21
deficiency (congenital adrenal hyperplasia, CAH). These families account for two
thirds (85/119) of all diagnosed patients of Finnish descent found in this
country. We recently demonstrated that multiple founder mutations each associated
with a particular haplotype can be found in Finland. Interestingly, some of the
haplotypes were identical to those observed in various European populations,
whereas others have not been described elsewhere, indicating a local and perhaps
a more recent origin. In the present report we show that each of the major
founder haplotypes originates from a particular geographic region of Finland.
Thus many local genetic isolates are to be expected in Finland. Our finding is in
a clear contrast to the genetic diseases known as the 'Finnish disease heritage',
in which only one mutation usually predominates. Some of the CYP21 haplotypes
proved very informative for analysis of the history of the Finnish population.
For example, the origin of one frequent haplotype was shown to cluster in a
region assumed by archaeological data to be a major site of immigration by
settlers of either Scandinavian or Baltic origin during the first centuries AD.
As this haplotype is frequent in many European patient populations, we provide
independent genetic evidence of this Iron Age immigration. On the other hand,
another frequent haplotype found solely in Finland reflects a more recent (post
15th century) settlement expansion. Consequently, well characterised and
sufficiently frequent autosomal gene markers can provide useful information on
migrations both between and within populations.
PMID- 10196703
TI - Mortality risk in men is associated with a common mutation in the methylene
tetrahydrofolate reductase gene (MTHFR).
AB - An elevated level of homocysteine in plasma is associated with the occurrence of
cardiovascular disease. A common ala-to-val mutation in the
methylenetetrahydrofolate reductase gene (MTHFR) is associated with an elevated
level of plasma homocysteine. We studied the possible detrimental effects of the
MTHFR mutation on mortality. Within a population-based study in the city of
Leiden, the Netherlands, we first compared the MTHFR genotype distribution among
365 elderly subjects aged 85 years and over born in Leiden, and 250 young
subjects aged 18 to 40 years whose families originated from the same geographical
region. Second, the complete cohort of 666 subjects aged 85 years and over was
followed over a period of 10 years for all-cause and cause-specific mortality and
stratified according to MTHFR genotype. The frequency of the MTHFR mutation was
significantly lower in the elderly than in the young (0.30 and 0.36,
respectively; P = 0.03). The difference in genotype distribution was only present
in men. The estimated mortality risk up to 85 years in men carrying the vallval
genotype was 3.7 (95% confidence interval (CI), 1.3-10.9). Over the age of 85,
mortality in men with the vallval genotype was increased 2.0-fold (95% CI, 1.1
3.9) and appeared to be attributable to cancer rather than cardiovascular causes
of death. Among women aged 85 years and over, no deleterious effect of the MTHFR
mutation was observed. In conclusion, the MTHFR mutation is associated with
increased mortality in men in middle and old age, but not in women.
PMID- 10196704
TI - Nephronophthisis in Finland: epidemiology and comparison of genetically
classified subgroups.
AB - Nephronophthisis--medullary cystic kidney disease is a progressive chronic
tubulointerstitial nephritis leading to terminal renal failure. About two thirds
of the patients with familial juvenile nephronophthisis, an autosomal recessive
disease, have a homozygous deletion at the gene locus on 2q13. Through a
nationwide search, 59 patients were ascertained in Finland. The incidence was
1:61,800 live births when calculated over a 20-year period. Of the patients, 17
came from four families showing dominant inheritance and 37 patients from 28
apparently recessive families when classified by family history, clinical
features or presence of a deletion on 2q13. Two were considered as new dominant
mutations; three sporadic patients could not be classified. The most significant
difference between the patients with deletions, patients without deletions but
having recessive family history, and patients belonging to families with dominant
inheritance was the age at first symptoms, at the start of dialysis and at
transplantation. These facts will be of help in determining the mode of
inheritance of a sporadic patient without a deletion.
PMID- 10196705
TI - Feasibility and acceptance of screening for fragile X mutations in low-risk
pregnancies.
AB - Fragile X syndrome is the second leading cause of mental retardation after Down
syndrome. Most women carriers of the fragile X mutation are unaware of their
condition. We critically evaluated whether screening pregnant women at low risk
for FMR1 mutation would be feasible as a routine part of antenatal care in
general practice. We also studied acceptance and attitudes to gene testing. From
July 1995 until December 1996, a carrier test was offered at the Kuopio City
Health Centre free of charge to all pregnant women in the first trimester
following counselling given by midwives on fragile X syndrome. All women found to
be carriers of FMR1 gene mutations underwent detailed genetic counselling and
were offered prenatal testing. Attitudes towards the gene test were elicited by
questionnaire. Most pregnant women (85%) elected to undertake the gene test. Six
women were found to be carriers (a rate of 1 in 246), and all subsequently
accepted prenatal testing. Three foetuses had a normal FMR1 gene, one had a large
premutation, one a 'size mosaic' mutation pattern, and another a full mutation.
This observational and interventional study demonstrates that antenatal screening
provides an effective way of identifying carriers and incorporating prenatal
testing into this process.
PMID- 10196706
TI - A European pilot quality assessment scheme for molecular diagnosis of
Huntington's disease.
AB - This paper reports a European pilot External Quality Assessment (EQA) scheme for
the molecular diagnosis of Huntington's disease (HD). The European Molecular
Genetics Quality Network (EMQN) chose HD as a relatively simple assay that allows
a range of difficulty in terms of technical competence and interpretation.
Fourteen centres from 12 different countries participated. The scheme organiser
provided five cases together with mock clinical information. The participating
laboratories were asked to complete the analyses and return the reports in
English to their normal laboratory format within a fixed period. The scheme
demonstrates a level of potential misdiagnosis in molecular analysis of HD as
well as a wide variety in way of reporting laboratory results. Overall 9/146
(6.2%) of alleles fell outside the set limits, and the rate of misdiagnosis was
1/78 (1.3%). A closer estimate of diagnostic accuracy will require expansion of
the scheme.
PMID- 10196707
TI - Asynchronous replication of alleles in genomes carrying an extra autosome.
AB - Transcriptional activity of genes appears to be highly related to their
replication timing; alleles showing the common biallelic mode of expression
replicate highly synchronously, whereas those with a monoallelic mode of
expression replicate asynchronously. Here we used FISH to determine the level of
synchronisation in replication timing of alleles in amniotic fluid cells derived
from normal foetuses and from those with either of the trisomies for autosomes
21, 18 or 13, or for sex chromosomes (47,XXX and 47,XXY). Two pairs of alleles,
not associated with the extra chromosome, were studied in subjects with each
trisomy and three in normal subjects. In cells derived from normal foetuses and
from foetuses with sex chromosome trisomies, each pair of alleles replicated
synchronously; yet these very same alleles replicated asynchronously in cells
derived from foetuses with trisomy for any of the three autosomes studied. The
results suggest that the gross phenotypic abnormalities associated with an extra
autosome are brought about not only by over-expression of genes present in three
doses, but also by modifications in the expression of genes present in the normal
two doses.
PMID- 10196708
TI - Cytogenetic analysis of sperm chromosomes and sperm nuclei in a male heterozygous
for a reciprocal translocation t(5;7)(q21;q32) by in situ hybridisation.
AB - We have studied the meiotic segregation of a reciprocal translocation
t(5;7)(q21;q32) in a male carrier, using the human sperm-hamster oocyte fusion
technique and the whole chromosome painting. A total of 296 sperm complements
were analysed by dual chromosome painting. The frequencies of alternate, adjacent
1, adjacent-2 and 3:1 segregation were 49.7%, 32.4%, 16.2% and 1.7% respectively.
Aneuploidy frequencies for chromosomes not involved in the translocation were
determined by FISH on decondensed sperm heads using probes from chromosomes X, Y,
6, 18 and 21. A total of 20,118 spermatozoa was analysed, 10,201 by two-colour
FISH (probes for chromosomes 6 and 21) and 9917 by three-colour FISH (probes for
chromosomes X, Y, and 18). There was no evidence of an interchromosomal effect,
since disomy frequencies were within the range of normal controls.
PMID- 10196709
TI - Direct estimation of the recombination frequency between the RB1 gene and two
closely linked microsatellites using sperm typing.
AB - In this study, single sperm typing has been used for high-resolution
recombination analysis between the retinoblastoma gene and two closely linked
extragenic microsatellites (D13S284 and D13S1307). The analysis of 1198 single
sperm from three donors allowed the determination of recombination fractions
between RB1.20 and D13S284 and RB1.20 and D13S1307 of 0.022 and 0.033,
respectively. These results show that RB1 gene and the two microsatellites are
closely linked, which validates their potential use in indirect genetic diagnosis
of retinoblastoma.
PMID- 10196710
TI - DFNB20: a novel locus for autosomal recessive, non-syndromal sensorineural
hearing loss maps to chromosome 11q25-qter.
AB - Autosomal recessive non-syndromal deafness is an extremely heterogeneous
condition with at least 19 loci (DFNB1-19) already described. We have used
autozygosity mapping to localise a further novel locus, DFNB20, to chromosome
11q25-qter in a consanguineous family originating from Pakistan. A region of
homozygosity was observed in affected individuals spanning the interval D11S969
qter.
PMID- 10196711
TI - No evidence for involvement of KCNN3 (hSKCa3) potassium channel gene in familial
and isolated cases of schizophrenia.
AB - Several studies have reported in schizophrenia a decrease of age of onset in
successive family generations, and this observation is consistent with
anticipation. Anticipation is known to result from expansion of CAG repeats in
several neurodegenerative disorders. Longer alleles of the KCNN3 gene, which
contains a highly polymorphic CAG repeat, and encodes a neuronal small
conductance calcium-activated potassium channel, have recently been shown to be
over-represented in sporadic cases of schizophrenia. In this report, we tested
the hypothesis of an association between longer alleles of CAG repeat in the
KCNN3 gene and schizophrenia in 20 families with clinical evidence for
anticipation and in 151 unrelated schizophrenic cases. No significant difference
in the distributions of allele frequencies was observed between familial cases of
schizophrenia and controls, and between unrelated cases and controls.
Furthermore, no intergenerational CAG repeat instability was detected in the 20
families. Our results do not support the involvement of the KCNN3 (hSKCa3) gene
in the etiology of schizophrenia.
PMID- 10196713
TI - Mutation in the zonadhesin-like domain of alpha-tectorin associated with
autosomal dominant non-syndromic hearing loss.
AB - A gene responsible for autosomal dominant non-syndromic hearing impairment in two
families (DFNA8 and DFNA12) has recently been identified as TECTA encoding alpha
tectorin, a major component of the tectorial membrane. In these families,
missense mutations within the zona pellucida domain of alpha-tectorin were
associated with stable severe mid-frequency hearing loss. The present study
reports linkage to DFNA12 in a new family with autosomal dominant high frequency
hearing loss progressing from mild to moderate severity. The candidate region
refined to 3.8 cM still contained the TECTA gene. A missense mutation (C1619S)
was identified in the zonadhesin-like domain. This mutation abolishes the first
of the vicinal cysteines (1619Cys-Gly-Leu- 1622Cys) present in the D4 von
Willebrand factor (vWf) type D repeat. These results further support the
involvement of TECTA mutations in autosomal dominant hearing impairment, and
suggest that vicinal cysteines are involved in tectorial membrane matrix
assembly.
PMID- 10196712
TI - Further evidence for the organisation of the four sarcoglycans proteins within
the dystrophin-glycoprotein complex.
AB - Based on the pattern of distribution of the SG proteins in patients with LGMD2C
and 2D, and on the observed decreased abundance of dystrophin through WB in some
sarcoglycans (SG) patients, we have recently suggested that alpha, beta and delta
subunits of sarcoglycan complex might be more closely associated and that gamma
SG might interact more directly with dystrophin. Two additional SG patients here
reported give further support to these suggestions: an LGMD2F patient showed
patchy labelling for gamma-SG, despite the lack of staining of the other three SG
proteins; an LGMD2C boy showed deficiency in dystrophin by means of WB and IF,
comparable with an DMD manifesting carrier. These two patients represent further
evidence of a closer relation of alpha, beta and delta-SG than of gamma-SG and of
the possible association of gamma-SG with dystrophin. In addition the LGMD2C
patient illustrates the potential risk of misdiagnosis using only dystrophin
analysis, in cases with no positive family history, or when DNA analysis is not
informative.
PMID- 10196715
TI - Experimentally observed germline mutations at human micro- and minisatellite
loci.
AB - We have analysed close to 30,000 human germline transmission events at five
microsatellite loci (D3S1359, HumTH01, HumvWA, HumTPO and HumFES) and four
minisatellite loci (D1S80, ApoB, Col2A1 and D17S30). At these loci the mutation
rates are similar at the microsatellite and the minisatellite loci, varying from
0.2 x 10(-3) to < 3.3 x 10(-3) and from 0.5 x 10(-3) to 1.5 x 10(-3),
respectively. Interestingly, paternal mutations appeared to be dominant at the
microsatellite loci, whilst maternal mutations are dominant at minisatellite
loci. Based on our data, no unequivocal support for a strict strand-slippage
mutation mechanism (gain or loss of a single repeat) was found, although the vast
majority of the mutational events were small gains or losses of one to three
repeats, and only few unequivocal large gains or losses were observed.
PMID- 10196714
TI - Haplotypes and mutations of the PAH locus in Egyptian families with PKU.
AB - A high degree of molecular heterogeneneity at the phenylalanine hydroxylase (PAH)
locus was established by examining RFLP haplotypes and PAH mutations in the
families of 13 Egyptians with phenylketenouria (PKU). Thirteen different
haplotypes were unequivocally determined in these kindreds. Haplotypes 1.8, 3.9,
4.3, 7.8, 22.11, 27.6, and 52.8 were found segregating with normal chromosomes,
whilst haplotypes 1.8, 5.9, 23.8, 32.8, the newly assigned 73.9, and two as yet
incomplete but novel haplotypes were found segregating with the mutant
chromosomes. There was no particular preference for a single haplotype among
normal or mutant chromosomes. Nine different mutations were also identified among
the 26 alleles. IVS 10nt11g (8/26), IVS 2nt5g-c (4/26), R261Q (3/26), R176X
(2/26), Y206D (2/26), S231P (2/26), Y198fs [593-614del22bp]; (2/26), G46fs
[136/137delG]; (1/26), and E178G (1/26). Six of these mutations (IVS 2nt5g-c,
R176X, Y198fs, R261Q, S231P, and IVS 10nt11g) are common to other Mediterranean
populations. Two mutations not previously reported in the Mediterranean basin
were also observed (Y206D and G46fs). These intriguing preliminary findings
confirm IVS 10nt11g as a major mutation among Mediterranean mutations and
demonstrate the need for a more comprehensive study of Arab populations to
confirm the uniqueness of the two novel mutations to the Egyptian population.
PMID- 10196716
TI - Unilateral hypoxic-ischemic injury in the neonatal rat brain evaluated by in vivo
MRI. Correlation with histopathology and neuroprotection by MK-801.
AB - RATIONALE AND OBJECTIVES: MRI was used for the in vivo evaluation of unilateral
hypoxic-ischemic brain injury and the evaluation of MK-801 in the neonatal rat.
METHODS: T2-weighted scans were obtained during the acute phase of HI injury and
3 months later. Histology was performed to correlate MRI signal changes with
pathology. Finally, the effectiveness of MK-801 to limit brain injury was
regionally assessed in vivo using T2-weighted MRI. RESULTS: Injury visualized by
MRI at 72 hours after hypoxia correlated strongly with histopathologic analysis.
Transient injury was identified. MK-801 significantly reduced the lesion extent
at the level of the hippocampus. Patterns of unilateral versus bilateral neonatal
brain injury were found to differ. CONCLUSIONS: The study demonstrates unique
patterns of brain injury not seen in adult animal hypoxia-ischemia studies, and
the sensitivity of the corpus callosum to hypoxia-ischemia. MK-801, although
neuroprotective, did not offer any selective neuroprotective benefit.
PMID- 10196717
TI - Neurotolerability of gadobenate dimeglumine in a rat model of focal brain
ischemia: EEG evaluation.
AB - RATIONALE AND OBJECTIVES: The neurologic pathologies for which contrast-enhanced
MRI is indicated are often accompanied by a disruption of the blood-brain barrier
(BBB), which allows the contrast agent to come into contact with the nervous
tissue. Thus, assessment of the neurologic safety for a new contrast agent is of
crucial importance. The objective of this study was to assess the
neurotolerability of the new MRI contrast agent gadobenate dimeglumine using EEG
in the presence of focal lesions of the BBB. METHODS: Lesions of the BBB were
obtained inducing a photochemical ischemia in rats. Gadobenate dimeglumine was
intravenously administered at 4.0 mmol/kg. An EEG was recorded during sleep/awake
behavior and was analyzed for pathologic tracing and for changes in spectral
content in terms of total power and frequency index. The presence of the BBB
lesions was verified using high-performance liquid chromatography measurement of
the gadobenate ion content in the brain. RESULTS: Gadobenate dimeglumine did not
have any epileptogenic effect in ischemic rats. However, it caused a transitory
shift of the EEG power spectrum toward the 0.5 to 9 Hz frequency bands of the
lesioned hemisphere during quiet wake. In the lesioned cortex, higher levels of
gadobenate ion were found until 3 hours after administration. CONCLUSIONS: In
experimental conditions of focal brain ischemia associated with BBB lesions,
gadobenate dimeglumine was well tolerated up to doses even 10 times higher than
the maximum clinical dose (0.3 mmol/kg) intended for brain imaging procedures.
PMID- 10196718
TI - Acoustic properties of NC100100 and their relation with the microbubble size
distribution.
AB - RATIONALE AND OBJECTIVES: NC100100 is a contrast agent for medical imaging with
ultrasonography consisting of stabilized gas microbubbles in an aqueous
suspension. The objective of this article is to explore the acoustic properties
of NC100100 and their relation with the microbubble size distribution. The
results are used to motivate the choice of a suitable assay/dosage parameter for
precise control of product efficacy. METHODS: The concentration and size
distribution of microbubbles in > 50 preparations of NC100100 were determined by
Coulter counting, and the acoustic attenuation and backscatter efficacy were
determined for all samples. The in vivo efficacy of the product was investigated
by harmonic imaging of the heart in a dog model. RESULTS: The results
demonstrated that the attenuation and backscatter efficacy per microbubble volume
vary strongly with size, showing distinct maxima with respect to microbubble
diameter. Sizes for optimal attenuation per volume ranged from 2.6 to 5.8
microns, depending on ultrasound frequency. The contribution of the smaller end
tail of the microbubble distribution was shown to be negligible. From the
observed size dependency for the acoustic properties, the volume concentration of
microbubbles was chosen as the assay/dosage parameter for NC100100. The accuracy
of this parameter as a descriptor of product efficacy was demonstrated by
precise, linear relations between volume, concentration, and
attenuation/backscatter. In comparison, the correlation between the microbubble
number and acoustic properties was not significant. Results from the in vivo
study showed a precise, linear relation between injected microbubble volume and
the observed in vivo efficacy. CONCLUSIONS: The acoustic properties of NC100100
are dependent on microbubble size. The observed batch-to-batch variance in the
acoustic properties of the product may be fully explained by variation in
concentration and size. Microbubble volume is a more precise predictor of in
vitro/in vivo efficacy than microbubble number and consequently was chosen as the
assay/dosage parameter for NC100100.
PMID- 10196719
TI - Reliability of technetium-99m Q12 and thallium-201 myocardial activity
measurements after triphenyl tetrazolium chloride myocardial staining by
perfusion.
AB - RATIONALE AND OBJECTIVES: Investigations in animal models of severe myocardial
ischemia or infarction use triphenyl tetrazolium chloride (TTC) staining to
document infarction size histologically and to correlate these data with uptake
measurements of radiolabeled tracers. Previously published data suggest that TTC
staining itself has an important impact on myocardial tracer activity
measurements. The authors hypothesized that TTC staining by perfusion has no
significant effect on relative regional myocardial activity measurements of
technetium-99m Q12 and thallium-201 in an open-chest canine model. METHODS: Eight
dogs underwent left anterior descending artery occlusion for 2 hours with 30
minutes of reperfusion, followed immediately by injection of technetium-99m Q12
(n = 4) or thallium-201. Total myocardial activity was recorded in a dose
calibrator, and regional myocardial samples were obtained by Cope needle biopsies
from the ischemic and normal zones, both before and after TTC staining. RESULTS:
The mean percent activity retention for the whole heart after perfusion staining
with TTC was significantly reduced when compared to the preperfusion value for
both technetium-99m Q12 and thallium-201. Regional measurements revealed no
significant difference between the mean percent retention of technetium-99m Q12
in the ischemic and normal zones. After TTC perfusion, regional mean percent
retention of thallium-201 was similar in the ischemic and normal zones.
CONCLUSIONS: In a canine model of myocardial ischemia and infarction with
reperfusion, TTC staining can be performed by coronary artery perfusion without
significantly affecting comparative regional measurements of either technetium
99m Q12 or thallium-201. Whole heart tracer retention is significantly reduced by
TTC perfusion staining, but thallium-201 is more affected than technetium-99m
Q12.
PMID- 10196720
TI - Image mottle in abdominal CT.
AB - RATIONALE AND OBJECTIVES: To investigate image mottle in conventional CT images
of the abdomen as a function of radiographic technique factors and patient size.
METHODS: Water-filled phantoms simulating the abdomens of adult (32 cm in
diameter) and pediatric (16 cm in diameter) patients were used to investigate
image mottle in CT as a function of x-ray tube potential and mAs. CT images from
39 consecutive patients with noncontrast liver scans and 49 patients with iodine
contrast scans were analyzed retrospectively. Measurements were made of the mean
liver parenchyma Hounsfield unit value and the corresponding image mottle.
RESULTS: For a given water phantom and x-ray tube potential, image mottle was
proportional to the mAs-0.5. Increasing the phantom diameter from 16 cm
(pediatric) to 32 cm increased the mottle by a factor of 2.4, and increasing the
x-ray tube potential from 80 kVp to 140 kVp reduced the mottle by a factor of
2.5. All patients were scanned at 120 kVp, with no correlation between patient
size and the x-ray tube mAs. The mean mottle level was 7.8 +/- 2.2 and 10.0 +/-
2.5 for the noncontrast and contrast studies, respectively. An increase in
patient diameter of 3 cm would require approximately 65% more mAs to maintain the
same level of image mottle. CONCLUSIONS: The mottle in abdominal CT images may be
controlled by adjusting radiographic technique factors, which should be adjusted
to take into account the size of the patient undergoing the examination.
PMID- 10196721
TI - NMRD investigation of DyDTPA- and GdDTPA-labeled starch particles. Selection of a
suitable suspension medium and influence of the starch matrix on relaxivity.
AB - RATIONALE AND OBJECTIVES: The primary aim was to investigate the influence of the
starch matrix on the T1 relaxivities of starch particles labeled with gadolinium
and dysprosium diethylenetriamine pentaacetic acid (GdDTPA-SP and DyDTPA-SP).
Achieving this required the selection of a medium that was suitable for
suspending the particles and that had field-independent T1 relaxation rates,
thereby eliminating errors in relaxivity determinations resulting from a field
dependent background. METHODS: GdDTPA-SP with low and high gadolinium content,
DyDTPA-SP, and empty DTPA-SP were suspended in an aqueous medium containing 5%
(w/w) of a polyethylene glycol-based block copolymer. 1/T1 NMRD profiles were
obtained in the temperature range of 5 degrees to 35 degrees C. RESULTS: Using
the block copolymer, particles did not settle, and samples could be prepared at a
low temperature to avoid particle degradation, the intrinsic T1 relaxation rate
of the suspension medium was field-independent and identical to that of water
from 25 degrees to 35 degrees C. The T1 relaxivities of DyDTPA-SP were higher
than those of dysprosium diethylenetriamine pentaacetate-bis(methylamide) (DyDTPA
BMA) and decreased with increasing magnetic field strength. The T1 relaxivity of
GdDTPA-SP was higher than that of GdDTPA at all fields, and decreased with
decreasing temperature and increasing gadolinium content. CONCLUSIONS: The GdDTPA
SP results showed that the particulate starch matrix served a dual role, with
opposing influences on relaxivity. It provided a means for increasing the
rotational correlation time (tau R), which resulted in higher relaxivities.
However, it also retarded radial diffusion of water molecules within the particle
interior, which significantly counteracted the enhancing effect of tau R. For
DyDTPA-SP, the starch matrix provided an additional diamagnetic contribution,
resulting in relaxivities higher than those of DyDTPA-BMA. The block copolymer
was suitable as a suspension medium for DyDTPA-SP and GdDTPA-SP and should also
be applicable for other particulates.
PMID- 10196722
TI - Comparison between a screen-film system and a selenium radiography system. An ROC
study using simulated thoracic lesions.
AB - RATIONALE AND OBJECTIVES: To evaluate the diagnostic image quality of the hard
copies of a commercially available selenium detector-based computed radiography
system compared to that of a conventional screen-film system. METHODS: Ten
radiographs of an anthropomorphic chest phantom with simulated nodular and linear
reticular lesions were produced using either system. Each radiograph was
subdivided into 15 fields containing zero lesions, one nodular lesion, one linear
reticular lesion, or both lesions. The total of 150 fields for each modality was
reviewed by six radiologists, and receiver operating analysis was performed.
RESULTS: The conventional screen-film system performed significantly better for
nodular lesions, whereas no statistically significant difference was found
between the detection rates of both systems for linear-reticular lesions.
CONCLUSIONS: The better detection of nodules with the dedicated selenium detector
can be explained by the higher dynamic range of the system. Detection of linear
reticular lesions was slightly but not significantly better with the screen-film
system, but the detection rate of the selenium detector might be further improved
with a different image processing technique.
PMID- 10196723
TI - Sources of error in lung densitometry with CT.
AB - RATIONALE AND OBJECTIVES: To determine and analyze the most important error
sources in lung CT densitometry in vivo. METHODS: The authors examined the
influences of CT acquisition errors, physiologic changes, and image segmentation
errors on lung densitometry. Among others, spatial dependency and long-term
reproducibility of the density measurements of blood and air were examined over a
period of 4 years in a group of 28 patients with pulmonary emphysema. These
results were related to the measured lung densities in this group. RESULTS: The
density measurement of blood and air is strongly dependent on the position in the
thorax. Despite full-scanner calibrations, x-ray tube replacement can induce a
significant increase in measured blood density. CONCLUSIONS: A change in a lung
density parameter over time can actually be the result of tube replacement or
changing blood density. A simple postprocessing technique can correct for these
changes.
PMID- 10196724
TI - Computer-aided diagnosis in full digital mammography.
AB - RATIONALE AND OBJECTIVES: The authors clarify the detection rates for breast
cancerous tumors and clustered microcalcifications with computer-aided diagnosis
(CAD) based on Fuji Computed Radiography. The authors also determine whether
mammographic reading with CAD contributes to the discovery of breast cancer.
METHODS: Data acquired by Fuji Computed Radiography 9000, which consisted of 4148
digital mammograms including 267 cases of breast cancer, was transferred directly
to an analysis workstation where an original software program determined
extraction rates for breast tumors and clustered microcalcifications.
Furthermore, using another 344 mammograms from 86 women, observer performance
studies were conducted on five doctors for receiver operating characteristic
(ROC) analysis. RESULTS: Sensitivity to breast cancerous tumors and clustered
microcalcifications were 89.9% and 92.8%, respectively false-positive rates were
1.35 and 0.40 per image, respectively. The observer performance studies indicate
that an average Az value for the five doctors was greater with the CAD system
than with a film-only reading without CAD, and that a reading with CAD was
significantly superior at P < 0.022. CONCLUSIONS: It has been shown that CAD
based on Fuji Computed Radiography offers good detection rates for both breast
cancerous tumors and clustered microcalcifications, and that the reading of
mammograms with this CAD system would provide potential improvement in diagnostic
accuracy for breast cancer.
PMID- 10196725
TI - Embolotherapy of aneurysms under temporary balloon occlusion of the neck. In
vitro study of a newly designed eccentric balloon catheter.
AB - RATIONALE AND OBJECTIVES: To test embolotherapy of aneurysms in an in vitro model
using standard and specially designed eccentric occlusion balloon catheters for
simultaneous delivery of the embolization agent and occlusion of the neck of the
aneurysm. METHODS: Two different in vitro set-ups were used: a bifurcational
aneurysm and an aneurysm with a straight parent vessel segment, both made from
elastic silicone and glass. Each model was exposed to a pulsating perfusion. The
effluent was collected and filtered. For the bifurcational aneurysms,
commercially available occlusion balloon catheters with a working channel exiting
at the tip were used. For the aneurysms with straight parent vessel, the
catheters were modified so that the balloon opened eccentrically. The working
channel of the catheter led to a side hole, which was located where the balloon
membrane was fixed to the catheter shaft. The aneurysms were filled with coils,
ethibloc, or hydrogel, and with coils combined with ethibloc or hydrogel, while
the expanded balloon occluded the neck. RESULTS: Embolization of aneurysms under
balloon occlusion of the neck was technically feasible with the catheter devices.
Dense packing with coils was possible in all cases without coil dislocation, but
unfilled interspaces remained between the coil wires. Best filling was achieved
with ethibloc or hydrogel alone or in combination with coils. During the filling
procedure, there was no distal embolization of the liquid agents. However, after
balloon deflation, considerable amounts of hydrogel or ethibloc were washed out
from the aneurysm. CONCLUSIONS: The results suggest that balloon occlusion of the
neck allows compact filling and minimizes the risk of dislocation in coil
embolotherapy of aneurysms. In nonbifurcational aneurysms, the eccentric balloon
catheter seems to be suitable for this treatment concept. Although liquid agents
may be safely delivered into the aneurysm under balloon protection, their
considerable washout rate after balloon removal requires further refinements of
the technique before clinical application is advisable.
PMID- 10196726
TI - Testosterone and men's health.
AB - Medical and behavioral research depicts the influence of testosterone on health
in opposite ways, the former finding beneficial effects and the latter
potentially detrimental ones. We investigate the relationship between
testosterone and health risk behavior, indicators of disease, and overall health
in a sample of 4393 men who were interviewed and medically examined. Analysis
revealed that having a high level of testosterone, compared to a low level,
increased the odds of health risk behavior. With respect to disease, high
testosterone increased the odds of some health problems but decreased the chances
of others. At very high levels testosterone loses many of its beneficial effects.
Overall, men with high testosterone would be healthier if they did not engage in
health risk behavior.
PMID- 10196727
TI - Exploring associations in developmental trends of adolescent substance use and
risky sexual behavior in a high-risk population.
AB - This study examined associations between the development of adolescent alcohol,
cigarette, and marijuana use and risky sexual behavior, over time, using latent
growth modeling methodology. Gender differences in the development and
relationships between use of substances and risky sexual behavior were also
examined. Participants were 257 adolescents (mean age = 15.96 years) assessed at
three time points over an 18-month period. The intercepts of marijuana with
cigarettes and alcohol, and all three substances with risky sexual behavior were
significantly related. Development of the three substances showed similar
patterns and development of cigarette use covaried with development of risky
sexual behavior. There were no significant differences for boys and girls in
these relationships. Results are discussed in relation to the need for greater
understanding of nonsexual and sex-related problem behaviors and for analyses
examining development and change in these behaviors during adolescence.
PMID- 10196728
TI - After-school supervision and adolescent cigarette smoking: contributions of the
setting and intensity of after-school self-care.
AB - This paper looks at the independent contributions of the setting and the
intensity of after-school self-care to the cigarette smoking behaviors of 2352
ninth graders. We controlled for a variety of correlates of adolescent cigarette
smoking that have not been accounted for in existing research. Results indicated
that the intensity of the self-care experience was significantly associated with
adolescent smoking behavior irrespective of the typical setting of the
adolescents' after-school activities. Our findings also indicated that a
nonpermissive parenting style, family rule-setting about cigarettes, and
especially, in absentia parental monitoring may reduce the likelihood of
cigarette smoking among latchkey and nonlatchkey adolescents alike. However,
latchkey youth were not any more sensitive to these aspects of parenting than
other adolescents. This is consistent with the notion that targeting these
aspects of the home lives of all adolescents has the potential to reduce smoking
behaviors among latchkey as well as nonlatchkey children.
PMID- 10196729
TI - The role of body dissatisfaction and bingeing in the self-esteem of women with
type II diabetes.
AB - This study investigated the impact of body dissatisfaction and binge eating on
self-esteem in women with Type II diabetes. The relationship of body
dissatisfaction and bingeing to perceived blood glucose control was also
assessed. Questionnaires were completed by a total of 215 women: 125 women with
Type II diabetes and 90 comparison women, who were roughly matched for age,
education, and ethnicity. When actual weight (BMI) was statistically controlled,
there was no difference between the groups in body dissatisfaction or bingeing
behavior. The women with diabetes, however, had significantly lower self-esteem.
Further, bingeing made a significant contribution to their self-esteem, in
contrast to the women without diabetes. For the women with diabetes, body
dissatisfaction and bingeing were also related to perceived blood glucose
control, although only bingeing remained significant when both variables were
entered into the regression equation. It was concluded that diabetes broadens the
domains of body dissatisfaction which are related to self-esteem.
PMID- 10196730
TI - Nonevaluative social support reduces cardiovascular reactivity in young women
during acutely stressful performance situations.
AB - We tested whether the presence of a stranger reduces cardiovascular responses
during stressful tasks if the evaluation potential of the stranger is minimized
and whether cardiovascular responses are affected by the quality of support in a
friendship. Undergraduate women performed stressful tasks in one of three
conditions: Alone, with a same-sex Stranger, or with a same-sex best Friend. The
stranger and friend could not hear participants' responses. Alone women had the
greatest increases in SBP and HR while women in the Stranger and Friend
conditions did not differ in their responses. In the Friend condition, HR
responses were smallest in women who were highly satisfied with the support that
they generally received from their friend. We conclude that the presence of a
nonevaluative friend or stranger can reduce cardiovascular responses and that the
quality of supportive ties modulates the impact of those ties on responses to
stress.
PMID- 10196731
TI - How many self-measured blood pressure readings are needed to estimate
hypertensive patients' "true" blood pressure?
AB - The present research was aimed at determining the number of self-measured blood
pressure (BP) readings needed to attain reliable estimates of true BP in
hypertensive patients. Correlation coefficients and standard deviation of
differences between pairs of measurements as well as generalizability theory were
applied to data from a controlled study on stress management training for
essential hypertension (Garcia-Vera et al., 1997). Forty-three hypertensive
patients self-recorded 48 readings of BP (at home and at work) at both the
pretreatment and the posttreatment (separated by a period of 2 months) and 24
readings of BP at follow-up (6 months after the pretreatment). The results showed
that it is enough to take two readings, one at work and the other at home, from
each of 3 consecutive days to get reliable estimates of SBP and DBP across
settings, over 1 week and over 2 months. This same criterion would be valid to
get reliable estimates of DBP over 6 months, but two readings, one at work and
the other at home, from 8 or more consecutive days may need to be taken to
achieve similarly reliable results for SBP.
PMID- 10196732
TI - Peritrophic matrix proteins.
AB - The peritrophic matrix (or peritrophic membrane) lines the gut of most insects at
one or more stages of the life cycle. It has important roles in the facilitation
of the digestive processes in the gut and the protection of the insect from
invasion by microorganisms and parasites. The traditional view of the peritrophic
matrix as a relatively insert sieve, composed largely of proteins and
glycosaminoglycans embedded in a chitinous matrix, is under revision as more is
learned about the molecular characteristics of the peritrophic matrix proteins.
This review summarizes emerging knowledge of the main protein constituents of the
peritrophic matrix. The availability of the first sequences of integral
peritrophic matrix proteins has coincided with the explosion of information in
sequence databases. It is therefore possible to examine common structural themes
in this family of proteins as well as in proteins of unknown location and
function from a variety of other insects, nematodes and viruses. The review
concludes with speculation about the biological functions of the proteins in this
matrix.
PMID- 10196733
TI - Satellite DNA transcription in Diadromus pulchellus (Hymenoptera).
AB - Previous studies have shown that the satellite DNAs in Hymenoptera account for 1
25% of the genome. They mainly correspond to a single family, or to several
subfamilies having the same evolutionary origin. We have now showed that the
satellite DNAs in the genomes of the hymenopterans Diadromus pulchellus,
Diadromus collaris, Eupelmus vuilletti and Eupelmus orientalis are transcribed in
both males and females. Satellite DNA transcripts could only be extracted with
NP40/Urea, indicating that they are strongly associated with proteins. The
satellite DNA in D. pulchellus was transcribed on the two DNA strands. The
satellite DNA transcripts were single-stranded and not polyadenylated in vivo.
The transcripts were found in embryos, larvae and imagos stages. The transcripts
detected included one major transcript (1.9 kb) and several discrete smaller
transcripts. The in vivo synthesis of these satellite DNA transcripts was
explored by identifying their putative initiation sites.
PMID- 10196734
TI - Molecular basis for thermoprotection in Bemisia: structural differences between
whitefly ketose reductase and other medium-chain dehydrogenases/reductases.
AB - The silverleaf whitefly (Bemisia argentifolii, Bellows and Perring) accumulates
sorbitol as a thermoprotectant in response to elevated temperature. Sorbitol
synthesis in this insect is catalyzed by an unconventional ketose reductase (KR)
that uses NADPH to reduce fructose. A cDNA encoding the NADPH-KR from adult B.
argentifolii was cloned and sequenced to determine the primary structure of this
enzyme. The cDNA encoded a protein of 352 amino acids with a calculated molecular
mass of 38.2 kDa. The deduced amino acid sequence of the cDNA shared 60% identity
with sheep NAD(+)-dependent sorbitol dehydrogenase (SDH). Residues in SDH
involved in substrate binding were conserved in the whitefly NADPH-KR. An
important structural difference between the whitefly NADPH-KR and NAD(+)-SDHs
occurred in the nucleotide-binding site. The Asp residue that coordinates the
adenosyl ribose hydroxyls in NAD(+)-dependent dehydrogenases (including NAD(+)
SDH), was replaced by an Ala in the whitefly NADPH-KR. The whitefly NADPH-KR also
contained two neutral to Arg substitutions within four residues of the Asp to Ala
substitution. Molecular modeling indicated that addition of the Arg residues and
loss of the Asp decreased the electric potential of the adenosine ribose-binding
pocket, creating an environment favorable for NADPH-binding. Because of the
ability to use NADPH, the whitefly NADPH-KR synthesizes sorbitol under
physiological conditions, unlike NAD(+)-SDHs, which function in sorbitol
catabolism.
PMID- 10196735
TI - Cloning of soluble alkaline phosphatase cDNA and molecular basis of the
polymorphic nature in alkaline phosphatase isozymes of Bombyx mori midgut.
AB - A cDNA coding for soluble type alkaline phosphatase (sALP) of Bombyx mori was
isolated. Deduced amino acid sequence showed high identities to various ALPs and
partial similarities to ATPase of Manduca sexta. Using this cDNA sequence as a
probe, the molecular basis of electrophoretic polymorphism in sALP and membrane
bound type ALP (mALP) was studied. As for mALP, the result suggested that post
translational modification was important for the proteins to express activity and
to represent their extensive polymorphic nature, whereas the magnitude of
activities was mainly regulated by transcription. On the other hand, sALP
zymogram showed poor polymorphism, but one exception was the null mutant, in
which the sALP gene was largely lost. Interestingly, the sALP gene was shown to
be transcribed into two mRNAs of different sizes, 2.0 and 2.4 Kb. In addition to
the null mutant of sALP, we found a null mutant for mALP. Both of these mutants
seem phenotypically silent, suggesting that the functional differentiation
between these isozymes is not perfect, so that they can still work mutually and
complement each other as an indispensable enzyme for B. mori.
PMID- 10196736
TI - Differential distribution of pyrokinin-isoforms in cerebral and abdominal
neurohemal organs of the American cockroach.
AB - Different pyrokinin isoforms were identified from major neurohemal organs of the
American cockroach. During their isolation they were recognized by bioassay using
a hyperneural muscle preparation that is sensitive to pyrokinins. All structures
were elucidated by sequence analysis and mass spectrometry. The primary
structures of the novel peptides isolated from the retrocerebral complex are
LVPFRPRL-NH2 (designated Pea-PK-3) and DHLPHDVYSPRL-NH2 (designated Pea-PK-4). A
pyrokinin, labeled Pea-PK-5, was isolated from abdominal perisympathetic organs.
Structural analysis of this peptide yielded the sequence GGGGSGETSGMWFGPRL-NH2.
The threshold concentrations of the identified pyrokinins for an eliciting effect
on contractions of the hyperneural muscle preparations differed dramatically.
This indicates that the different distribution of pyrokinin-isoform observed in
neurohemal organs may be associated with different functions. This is the first
report of a differential distribution of peptide-isoforms in the neurohemal
organs of insects.
PMID- 10196737
TI - Isolation and characterisation of a cytochrome b5 cDNA clone from Helicoverpa
armigera (Hubner): possible involvement of cytochrome b5 in cytochrome P450
CYP6B7 activity towards pyrethroids.
AB - A cDNA clone specific for cytochrome b5 was isolated from Helicoverpa armigera.
This sequence corresponded to a mRNA of an estimated 544 nucleotides in length
excluding the poly A tail. The mRNA contained an open reading frame of 381
nucleotides encoding a protein of 127 amino acid residues with a molecular weight
of 14,564 Daltons. The encoded protein sequence showed 51% protein sequence
identity with cytochrome b5 from M. domestica and 36-37% identity with mammalian
and avian cytochrome b5 sequences. Northern analysis of larval RNA using this
cDNA as probe, revealed that cytochrome b5 mRNA expression is tissue specific
with the mRNAs being expressed in abundance in the midguts of larvae, at a lower
level in fatbody but is not detectable in larval integument. During normal
development this mRNA was undetectable in eggs but was present at similar levels
from first to fifth instar larvae. The mRNA was expressed at very low levels in
pupae and adult moths. The cytochrome b5 mRNA was found to be inducible by
treatment with the monoterpene, a-pinene, and to be over-expressed in some
individuals of a pyrethroid resistant population of H. armigera. The induction
and over-expression patterns were identical to the cytochrome P450, CYP6B7 mRNA.
The present data suggests that cytochrome b5 may be involved in CYP6B7 mediated
pyrethroid resistance in H. armigera.
PMID- 10196738
TI - Wolbachia infections are distributed throughout insect somatic and germ line
tissues.
AB - Wolbachia are intracellular microorganisms that form maternally-inherited
infections within numerous arthropod species. These bacteria have drawn much
attention, due in part to the reproductive alterations that they induce in their
hosts including cytoplasmic incompatibility (CI), feminization and
parthenogenesis. Although Wolbachia's presence within insect reproductive tissues
has been well described, relatively few studies have examined the extent to which
Wolbachia infects other tissues. We have examined Wolbachia tissue tropism in a
number of representative insect hosts by western blot, dot blot hybridization and
diagnostic PCR. Results from these studies indicate that Wolbachia are much more
widely distributed in host tissues than previously appreciated. Furthermore, the
distribution of Wolbachia in somatic tissues varied between different
Wolbachia/host associations. Some associations showed Wolbachia disseminated
throughout most tissues while others appeared to be much more restricted, being
predominantly limited to the reproductive tissues. We discuss the relevance of
these infection patterns to the evolution of Wolbachia/host symbioses and to
potential applied uses of Wolbachia.
PMID- 10196739
TI - The role of inositol 1,4,5-trisphosphate 5-phosphatase in inositol signaling in
the CNS of larval Manduca sexta.
AB - Production of inositol 1,4,5-trisphosphate (IP3) in cells results in the
mobilization of intracellular calcium. Therefore, the dynamics of IP3 metabolism
is important for calcium dependent processes in cells. This report investigates
the coupling of mAChRs to the inositol lipid pathway in the CNS of the larval
Manduca sexta. Stimulation of intact abdominal ganglia prelabeled with [3H]
inositol using a muscarinic agonist, oxotremorine-M (oxo-M), increased total
inositol phosphate levels in a dose dependent manner (EC50 = 4.23 microM). These
inositol phosphates consisted primarily of inositol 1,4-bisphosphate (IP2) and
inositol monophosphate (IP1). Similarly, when nerve cord homogenates were
provided with [3H]-phosphatidylinositol 4,5-bisphosphate ([3H]-PIP2) (10-13
microM) the predominant products were IP2 and IP1. In contrast, incubation of
purified membranes with 1 mM oxo-M in the presence of 100 microM GTP gamma S and
[3H]-PIP2 increased IP3 levels, suggesting that the direct activation of
phospholipase C (PLC) by mAChRs occurs in a membrane delimited process. Together,
these results suggest that in the intact nerve cord and in crude homogenates, a
cytosolic 5-phosphatase quickly metabolizes IP3 to produce to IP2 and IP1. This
enzyme was kinetically characterized using IP3 (Km = 43.7 microM, Vmax = 864
pmoles/min/mg) and IP4 (Km = 0.93 microM; Vmax = 300pmoles/min/mg) as substrates.
The enzyme activity can be potently inhibited by two IP thiol compounds; IP3S3
(1,4,6) and IP3S3 (2,3,5), that show complex binding kinetics (Hill numbers < 1)
and can distinguish different forms of the 5-phosphatase in purified membranes.
These two inhibitors could be very useful tools to determine the role of the
inositol lipid pathway in neuroexcitability.
PMID- 10196740
TI - Isolation and characterization of two digestive trypsin-like proteinases from
larvae of the stalk corn borer, Sesamia nonagrioides.
AB - Two digestive trypsin-like proteinases from Sesamia nonagrioides Lef.
(Lepidoptera: Noctuidae) larvae were purified by benzamidine-Sepharose affinity
chromatography. The purified enzymes showed molecular size of 27 (trypsin-I) and
24 KDa (trypsin-II). Amino acid analysis and N-terminal sequencing confirmed
their relationship with other trypsins from lepidopteran larvae. However, trypsin
I presented one lysine at position 11, being the first report of this amino acid
in the sequence of a lepidopteran digestive trypsin. Trypsin-I had an isoelectric
point of 6.0, and a Km of 2.2 x 10(-4) M and 3.9 x 10(-5) M for BApNa and BAEE,
respectively. Trypsin-II presented an isoelectric point of 8.7, and Km values of
1.7 x 10(-4) M (BApNa) and 3.8 x 10(-5) M (BAEE). Both enzymes were
differentially inhibited by some proteinase inhibitors. In particular, trypsin-I
was inhibited by E-64 (ID50 = 6 microM) but not by lima bean trypsin inhibitor
(LBI), whereas trypsin-II was inhibited by LBI (ID50 = 1 microM) and poorly by E
64 (ID50 = 85 microM). Changes in the susceptibility of the trypsin-like activity
of midgut extracts from different larval instars to these inhibitors suggest that
the relative proportion of these two enzymes varied through larval development,
being predominant in early instars trypsin-I and in late instars trypsin-II.
PMID- 10196741
TI - Mutations in the house fly Vssc1 sodium channel gene associated with super-kdr
resistance abolish the pyrethroid sensitivity of Vssc1/tipE sodium channels
expressed in Xenopus oocytes.
AB - The super-kdr insecticide resistance trait of the house fly confers resistance to
pyrethroids and DDT by reducing the sensitivity of the fly nervous system. The
super-kdr genetic locus is tightly linked to the Vssc1 gene, which encodes a
voltage-sensitive sodium channel alpha subunit that is the principal site of
pyrethroid action. DNA sequence analysis of Vssc1 alleles from several
independent super-kdr fly strains identified two amino acid substitutions
associated with the super-kdr trait: replacement of leucine at position 1014 with
phenylalanine (L1014F), which has been shown to cause the kdr resistance trait in
this species, and replacement of methionine at position 918 with threonine
(M918T). We examined the functional significance of these mutations by expressing
house fly sodium channels containing them in Xenopus laevis oocytes and by
characterizing the biophysical properties and pyrethroid sensitivities of the
expressed channels using two-electrode voltage clamp. House fly sodium channels
that were specifically modified by site-directed mutagenesis to contain the
M918T/L1014F double mutation gave reduced levels of sodium current expression in
oocytes but otherwise exhibited functional properties similar to those of
wildtype channels and channels containing the L1014F substitution. However,
M918T/L1014F channels were completely insensitive to high concentrations of the
pyrethroids cismethrin and cypermethrin. House fly sodium channels specifically
modified to contain the M918T single mutation, which is not known to exist in
nature except in association with the L1014F mutation, gave very small sodium
currents in oocytes. Assays of these currents in the presence of high
concentrations of cismethrin suggest that this mutation alone is sufficient to
abolish the pyrethroid sensitivity of house fly sodium channels. These results
define the functional significance of the Vssc1 mutations associated with the
super-kdr trait of the house fly and are consistent with the hypothesis that the
super-kdr trait arose by selection of a second-site mutation (M918T) that confers
to flies possessing it even greater resistance than the kdr allele containing the
L1014F mutation.
PMID- 10196742
TI - Serotyping of Campylobacter jejuni based on heat-stable antigens: relevance,
molecular basis and implications in pathogenesis.
PMID- 10196743
TI - The qacG gene on plasmid pST94 confers resistance to quaternary ammonium
compounds in staphylococci isolated from the food industry.
AB - The 2.3 kb resistance plasmid pST94 revealed a new gene (qacG) encoding
resistance to benzalkonium chloride (BC), a commonly used quaternary ammonium
disinfectant, and the intercalating dye ethidium bromide (Eb) in staphylococci
isolated from the food industry. The 107 amino acid QacG protein showing 69.2%
identity to the staphylococcal multi-drug resistance protein Smr is a new member
of the small multi-drug resistance (SMR) protein family. QacG conferred
resistance via proton dependent efflux. An additional ORF on pST94 encoded a
protein with extensive similarity to replication proteins of other Gram-positive
bacteria. Gene constructs containing the qacG and smr gene region combined with
the smr or qacG promoter, respectively, indicated that QacG is more efficient
than Smr and that qacG has a weaker promoter. Resistant qacG-containing cells
could be adapted to withstand higher concentrations of BC. Adapted qacG
containing cells showed increased resistance mainly to BC. In contrast,
adaptation of sensitive cells showed cross-resistance development to a range of
compounds. Induction of proton-dependent efflux was observed for BC-adapted
staphylococci cells not containing qacG. The ability of sublethal concentrations
of BC to develop cross-resistance and induce efflux mechanisms could be of
practical significance; it should be considered before use of any new
disinfectant and in the design of better disinfection procedures.
PMID- 10196744
TI - Fermentation extract effects on the morphology and metabolism of the rumen fungus
Neocallimastix frontalis EB188.
AB - The effects of Aspergillus oryzae fermentation extract, Amaferm, on the rumen
fungus Neocallimastix frontalis EB188 were studied. The secretion of cellulase
was increased by 67% and rhyzoid development was increased 3.8-fold in the
presence of extract. Strength of fungal response increased in a dose-dependent
manner and demonstrated a positive correlation between cell surface area and
enzyme secretion. Above certain concentrations of extract, however, the
development of the fungus and enzyme secretions remained at control values or
slightly diminished. Supernatant fluid appearance of the intracellular enzyme,
malate dehydrogenase, paralleled the secretion of cellulase both in the presence
and absence of extract. Ether solubilization of extract demonstrated that the
active component(s) possessed a moderately polar value between 2.7 and 2.8. Thin
layer chromatography separated extract into inert, inhibitory and intensely
stimulating fractions. These results support the idea that by accelerating fungal
growth and metabolism, Amaferm increases the rate (or extent) of fibre
degradation caused by rumen fungi and that this, in turn, may contribute to
enhanced animal performance.
PMID- 10196745
TI - The survival characteristics of a non-toxigenic strain of Escherichia coli
O157:H7.
AB - The survival characteristics of a non-toxigenic, antibiotic-resistant strain of
Escherichia coli O157:H7 in bovine faeces were investigated. Faecal samples were
inoculated with 10(8-9) cfu g-1 of the organism and (i) stored in closed plastic
containers at 10 degrees C, (ii) stored in closed plastic containers placed
outside or (iii) decanted onto the surface of grazing land. Recovery and
enumeration on Sorbitol MacConkey Agar (SMAC) and Tryptic Soya Agar (TSA)
revealed that the E. coli O157:H7 numbers in both enclosed samples (i and ii) had
decreased by 4.5-5.5 log10 cfu g-1 within 99 d. Numbers in samples decanted onto
grassland (iii) decreased by 4.0-5.0 log10 cfu g-1 within 50 d but the organism
was still detectable in the surrounding soil for up to 99 d. Persistence of E.
coli O157:H7 in bovine faeces and contaminated pastures may therefore be an
important factor in the initial infection and re-infection of cattle.
PMID- 10196746
TI - Isolation and characterization of two glycerol-fermenting clostridial strains
from a pilot scale anaerobic digester treating high lipid-content slaughterhouse
waste.
AB - Two obligately anaerobic bacterial strains were isolated from the contents of a
pilot scale, anaerobic digester treating slaughterhouse waste with a high protein
and lipid content. The isolates, LIP1 and MW8, were characterized as spore
forming, Gram-positive rods, capable of fermenting glycerol. Isolate LIP1 was
also observed to be lipolytic and was able to hydrolyse tallow and olive oil.
Both isolates grew optimally at 37 degrees C and formed either acetate and
formate (LIP1), or acetate and butyrate (MW8), as major glycerol fermentation
products. Both isolates produced ethanol as the major reduced fermentation end
product. Neither MW8 nor LIP1 had growth and metabolism inhibited by the addition
of stearic acid at concentrations normally considered bactericidal. Analysis of
the 16S rRNA gene sequences, in conjunction with the phenotypic data, confirmed
that the isolates are members of the genus Clostridium (sensu lato), clustering
with species of clostridial clusters I (MW8) and XIVa (LIP1).
PMID- 10196747
TI - Diversity of bacterial strains degrading hexadecane in relation to the mode of
substrate uptake.
AB - The relative distribution of the modes of hydrocarbon uptake, used by bacteria of
the environment for the degradation of long-chain alkanes, has been evaluated.
The first mode of uptake, direct interfacial accession, involves contact of cells
with hydrocarbon droplets. In the second mode, biosurfactant-mediated transfer,
cell contact takes place with hydrocarbons emulsified or solubilized by
biosurfactants. Sixty-one strains growing on hexadecane were isolated from
polluted and non-polluted soils and identified. The majority (61%) belonged to
the Corynebacterium-Mycobacterium-Nocardia group. Criteria selected for
characterizing hexadecane uptake were cell hydrophobicity, interfacial and
surface tensions and production of glycolipidic extracellular biosurfactants.
These properties were determined in flask cultures on an insoluble (hexadecane)
and on a soluble (glycerol or succinate) carbon source for a subset of 23
representative strains. Exclusive direct interfacial uptake was utilized by 47%
of studied strains. A large proportion of strains (53%) produced biosurfactants.
The data on cellular hydrophobicity suggested the existence of two distinct
alkane transfer mechanisms in this group. Accordingly, tentative assignments of
biosurfactant-mediated micellar transfer were made for 11% of the isolated
strains, and of biosurfactant-enhanced interfacial uptake for 42%.
PMID- 10196748
TI - Effect of elevated oxygen and carbon dioxide on the surface growth of vegetable
associated micro-organisms.
AB - The impact of a novel type of Modified Atmosphere (MA), referred to as high O2
MA, on micro-organisms associated with the spoilage of minimally-processed
vegetables was studied. Pure cultures of Pseudomonas fluorescens, Enterobacter
agglomerans, Aureobacterium strain 27, Candida guilliermondii, C. sake,
Salmonella typhimurium, Salm. enteritidis, Escherichia coli, Listeria
monocytogenes, Leuconostoc mesenteroides var. mesenteroides, Lactobacillus
plantarum and Lactococcus lactis were cultured on an agar-surface model system
and incubated at 8 degrees C under an atmosphere composed of O2 (80 or 90%,
balanced with N2), CO2 (10 or 20%, balanced with N2), or a combination of both
gases. In general, exposure to high O2 alone did not inhibit microbial growth
strongly, while CO2 alone reduced growth to some extent in most cases.
Consistently strong inhibition was observed only when the two gases were used in
combination. With minimally-processed vegetables, where CO2 levels of around 20%
or above cannot be used because of physiological damage to the produce, the
combined treatment of high O2 and 10-20% CO2 may provide adequate suppression of
microbial growth, allowing a safe, prolonged shelf-life.
PMID- 10196749
TI - Influence of organic matter, cations and surfactants on the antimicrobial
activity of Melaleuca alternifolia (tea tree) oil in vitro.
AB - The effect of some potentially interfering substances and conditions on the
antimicrobial activity of Melaleuca alternifolia (tea tree) oil was investigated.
Agar and broth dilution methods were used to determine minimum inhibitory and
cidal concentrations of tea tree oil in the presence and absence of each
potentially interfering substance. Activity was determined against Gram-positive
and -negative bacteria, and Candida albicans. Minimum inhibitory or cidal
concentrations differed from controls by two or more dilutions, for one or more
organisms, where Tween-20, Tween-80, skim-milk powder and bovine serum albumin
were assessed. These differences were not seen when assays were performed in
anaerobic conditions, or in the presence of calcium and magnesium ions. The
effect of organic matter on the antimicrobial activity of tea tree oil was also
investigated by an organic soil neutralization test. Organisms were exposed to
lethal concentrations of tea tree oil ranging from 1-10% (v/v), in the presence
of 1-30% (w/v) dry bakers' yeast. After 10 min contact time, viability was
determined. At > or = 1%, organic matter compromised the activity of each
concentration of tea tree oil against Staphylococcus aureus and C. albicans. At
10% or more, organic matter compromised the activity of each tea tree oil
concentration against Pseudomonas aeruginosa. Organic matter affected 1 and 2%
tea tree oil, but not 4 and 8%, against Escherichia coli. In conclusion, organic
matter and surfactants compromise the antimicrobial activity of tea tree oil,
although these effects vary between organisms.
PMID- 10196750
TI - X-ray microanalysis of chlorine and phosphorus content in biguanide-treated
Acanthamoeba castellanii.
AB - Energy dispersive analysis of X-rays (EDAX) was used to study the effects of
chlorhexidine diacetate (CHA) and polyhexamethylene biguanide (PHMB) on
Acanthamoeba castellanii. A high variation of elements occurred in untreated
individual cells and only two elements, Cl (a biocide marker) and P, were
investigated. X-ray dot mapping of untreated trophozoites and cysts revealed that
Cl in cells was uniformly distributed throughout the cytoplasm, whereas P was
less dense in the vacuoles. X-ray dots of Cl in biocide-treated trophozoites and
cysts appeared denser and evenly distributed within the cells as the biguanide
concentration increased. Quantitative analysis of either CHA or PHMB within the
cells using Cl as an elemental marker was unsatisfactory because of the high Cl
levels in untreated cells. The apparent increases of P in some experiments with
treated cells might be associated with reduced permeability, protein coagulation
or aggregation of phospholipids.
PMID- 10196751
TI - Genotypic and phenotypic relationships in Burkholderia cepacia isolated from
cystic fibrosis patients and the environment.
AB - Twenty-one strains of Burkholderia cepacia isolated from the environment, and 21
clinical strains isolated principally from sputum of cystic fibrosis (CF)
patients, were characterized genotypically by macrorestriction analysis (genome
fingerprinting) and PCR ribotyping, and phenotypically by susceptibility to
antibiotics and the ability to macerate onion tissue. The plasmid content of the
strains was also investigated. Environmental isolates showed a high degree of
genetic variability, all strains differing from both one another and the CF
isolates. The CF isolates were less variable, with common strains found in
patients attending three geographically distinct CF centres. Phenotypic variation
was found both within and between CF and environmental strains. Generally, CF
isolates displayed higher levels of antibiotic resistance, while the ability to
macerate onion tissue was more prevalent amongst environmental isolates. Plasmids
were more frequently found in CF isolates, but were of similar size in both
groups of strains. Such variability is not surprising in view of the existence of
multiple genomovars within the B. cepacia complex.
PMID- 10196752
TI - Effect of osmotic, alkaline, acid or thermal stresses on the growth and
inhibition of Listeria monocytogenes.
AB - Five strains of Listeria monocytogenes (a, b, c, d and e) isolated from
industrial plants have been subjected to different osmotic, alkaline, acid or
thermal stresses. The effects of these treatments on lag-phase (L) and growth
rate (mu) of cells in mid-log phase have been followed using an automated optical
density monitoring system. Increasing the osmotic pressure by the addition of
different amounts of NaCl increased the lag phase and decreased the growth rate.
The same phenomena were observed after decreasing the pH of the medium to 5.8,
5.6 or 5.4 by addition of acetic, lactic or hydrochloric acids. The inhibitory
effect was: acetic acid > lactic acid > hydrochloric acid. The addition of NaOH
to attain pH values of 9.5, 10.0, 10.5 or 11.0 in the medium produced a dramatic
increase of the lag phase at pH 10.5 and 11. Growth rates were also decreased
while the maximal population increased with high pH values. These effects varied
according to strains. Strains d and e were the most resistant to acidic and
alkaline stresses, and e was the most affected by the addition of NaCl. A cold
shock of 30 min at 0 degree C had limited effects on growth parameters. On the
other hand, hyperthermal shocks (55 or 63 degrees C, 30 min) led to similar
increased lag phases and to significant increases of the maximal population in
all five strains.
PMID- 10196753
TI - Unique activity associated with non-insecticidal Bacillus thuringiensis
parasporal inclusions: in vitro cell-killing action on human cancer cells.
AB - Parasporal inclusion proteins from a total of 1744 Bacillus thuringiensis
strains, consisting of 1700 Japanese isolates and 44 reference type strains of
existing H serovars, were screened for cytocidal activity against human leukaemia
T cells and haemolytic activity against sheep erythrocytes. Of 1684 B.
thuringiensis strains having no haemolytic activity, 42 exhibited in vitro
cytotoxicity against leukaemia T cells. These non-haemolytic but leukaemia cell
toxic strains belonged to several H-serovars including dakota, neoleonensis,
shandongiensis, coreanensis and other unidentified serogroups. Purified
parasporal inclusions of the three selected strains, designated 84-HS-1-11, 89-T
26-17 and 90-F-45-14, exhibited no haemolytic activity and no insecticidal
activity against dipteran and lepidopteran insects, but were highly cytocidal
against leukaemia T cells and other human cancer cells, showing different
toxicity spectra and varied activity levels. Furthermore, the proteins from 84-HS
1-11 and 89-T-26-17 were able to discriminate between leukaemia and normal T
cells, specifically killing the former cells. These findings may lead to the use
of B. thuringiensis inclusion proteins for medical purposes.
PMID- 10196754
TI - Rapid enumeration of physiologically active bacteria in purified water used in
the pharmaceutical manufacturing process.
AB - Physiologically active bacteria in purified water used in the manufacturing
process of pharmaceutical products were enumerated in situ. Bacteria with growth
potential were enumerated using the micro-colony technique and direct viable
counting (DVC), followed by 24 h of incubation in 100-fold diluted SCDB (Soybean
Casein Digest Broth) at 30 degrees C. Respiring and esterase-active bacteria were
detected by fluorescent staining with 5-cyano-2,3-ditolyl tetrazolium chloride
(CTC) and 6-carboxyfluorescein diacetate (6CFDA), respectively. A large number of
bacteria in purified water retained physiological activity, while most could not
form colonies on conventional media. The techniques applied in this study enabled
bacteria to be counted within 24 h so results could be available within one
working day. These rapid and convenient techniques should be useful for the
systematic monitoring of bacteria in water used for pharmaceutical manufacturing.
PMID- 10196755
TI - Differentiation between brewing and non-brewing yeasts using a combination of PCR
and RFLP.
AB - In order to differentiate brewing from non-brewing yeasts, a specific polymerase
chain reaction (PCR) which targeted the open reading frame of FLO1 was employed.
Non-brewing yeasts include 'non-brewing Saccharomyces yeasts' and 'non
Saccharomyces yeasts'. The molecular sizes of the PCR products differed between
brewing and non-brewing Saccharomyces yeasts. No FLO1 PCR products were obtained
from non-Saccharomyces yeasts. Specific PCR, using oligonucleotide primers that
targeted the region between the 5S and 26S rRNA genes, could be used to
differentiate brewing yeasts from some non-brewing yeasts. These PCR products
were digested with restriction enzymes, Scr FI and Msp I. Different restriction
profiles were obtained from brewing and non-brewing yeasts which could not be
differentiated using specific PCR of rDNA. These results suggest that it is
possible to identify brewing from non-brewing yeasts using specific PCR of FLO1
and rDNA, and detection of restriction fragment polymorphism of rDNA.
PMID- 10196756
TI - Genetic diversity among dairy lactococcal strains investigated by polymerase
chain reaction with three arbitrary primers.
AB - Randomly amplified polymorphic DNA (RAPD) has been used for the rapid typing of
Lactococcus lactis strains isolated from raw milk from the Camembert region of
Normandy. It is thought that the diversity and perhaps the area strain
specificity due to climatic and geographical factors of such wild-type
lactococcal strains could contribute to the flavour differences and specific
features detected for the same product in different areas. The patterns from 58
isolates were analysed by UPGMA dendrograms. At a similarity level of 50%, four
RAPD clusters were distinguished. Clusters 1 and 2 contained strains of
subspecies lactis and cluster 3 contained strains related to the C2 strain which
is genetically cremoris but phenotypically lactis. The type strain of cremoris
subspecies was significantly differentiated from these strains with primers P2
and P3. Thus, there was a real genetic diversity in pattern, making it possible
to detect potential typical RAPD fragments.
PMID- 10196757
TI - Resistant starch modifies gut microflora and microbial metabolism in human flora
associated rats inoculated with faeces from Italian and UK donors.
AB - The effect of sucrose and resistant starch ('CrystaLean'--a retrograded, amylose
starch) on human gut microflora and associated parameters was studied in human
flora-associated (HFA) rats, colonized with microfloras from UK or Italian
subjects, to determine whether such floras were affected differently by dietary
carbohydrates. Consumption of the resistant starch diet resulted in significant
changes in four of the seven main groups of bacteria enumerated. In both the UK
and Italian flora-associated rats, numbers of lactobacilli and bifidobacteria
were increased 10-100-fold, and there was a concomitant decrease in
enterobacteria when compared with sucrose-fed rats. The induced changes in caecal
microflora of both HFA rat groups were reflected in changes in bacterial enzyme
activities and caecal ammonia concentration. Although it had little effect on
caecal short-chain fatty acid concentration, CrystaLean markedly increased the
proportion of n-butyric acid in both rat groups and was associated with a
significant increase in cell proliferation in the proximal colon of the Italian
flora-associated rats. CrystaLean appeared to play a protective role in the colon
environment, lowering caecal ammonia concentration, caecal pH and beta
glucuronidase activity.
PMID- 10196758
TI - Intermittent shedding of thermophilic campylobacters by sheep at pasture.
AB - The rates at which sheep on different types of pasture shed campylobacters in
their faeces were measured over 12 months. Overall, shedding of campylobacters at
pasture was between a third and a half of the carriage rate (92%) of the
intestines of sheep at slaughter. Shedding was highest during saltmarsh grazing,
followed by upland fell and farm grazing. The rate of shedding varied at
different times of the year, with the highest rates (100%) coinciding with
lambing, weaning, and movement onto new pasture. The lowest rates (0%) occurred
when sheep were fed on hay and silage. On the farm, low rates occurred during the
whole of gestation, both when the sheep were indoors and outdoors. Campylobacter
jejuni was the main species isolated and survived for up to 4 d in sheep faeces.
Lambs became colonized by Campylobacter within 1-5 d of being born. Ewes, which
were not shedding campylobacters prior to lambing, started to shed after lambing,
and ewes which were shedding low numbers of Campylobacter before lambing,
increased the numbers of bacteria being shed after lambing.
PMID- 10196760
TI - Response to high-pressure, low-temperature treatment in vegetables: determination
of survival rates of microbial populations using flow cytometry and detection of
peroxidase activity using confocal microscopy.
AB - Application of high hydrostatic pressure (200, 300, 350 and 400 MPa) at 5 degrees
C for 30 min to different micro-organisms, including Gram-positive and Gram
negative bacteria, moulds and yeasts, proved to be more effective in inactivating
these organisms than treatments at 20 degrees C for 10 min and at 10 degrees C
for 20 min. Moulds, yeasts, Gram-negative bacteria and Listeria monocytogenes
were most sensitive, and their populations were completely inactivated at
pressures between 300 and 350 MPa. The same conditions of pressure, temperature,
and time were applied to different vegetables (lettuce, tomato, asparagus,
spinach, cauliflower and onion), achieving reductions of from 2-4 log units in
both viable mesophiles and moulds and yeasts at pressures of between 300 and 400
MPa. Sensory characteristics were unaltered, especially in asparagus, onion,
tomato and cauliflower, though slight browning was observed in cauliflower at 350
MPa. Flow cytometry was applied to certain of the microbial populations used in
the above experiment before and after the pressurization treatment. The results
were indicative of differing percentage survival rates depending on micro
organism type, with higher survival rates for Gram-positive bacteria, except L.
monocytogenes, than in the other test micro-organisms. Growth of survivors was
undetectable using the plate count method, suggesting that micro-organisms
suffering from pressure stress were metabolically inactive though alive. The
pressurization treatments did not inactivate the peroxidase responsible for
browning in vegetables. Confocal microscopic examination of epidermal tissue from
onion showed that the enzyme had been displaced to the cell interior. Use of low
temperatures and moderately long pressurization times yielded improved
inactivation of micro-organisms and better sensorial characteristics of the
vegetables, and should lower industrial costs.
PMID- 10196759
TI - Inositol polyphosphate-mediated iron transport in Pseudomonas aeruginosa.
AB - It has previously been shown that myo-inositol hexakisphosphate (myo-InsP6)
mediates iron transport into Pseudomonas aeruginosa and overcomes iron-dependent
growth inhibition. In this study, the iron transport properties of myo-inositol
trisphosphate and tetrakisphosphate regio-isomers were studied. Pseudomonas
aeruginosa accumulated iron (III) at similar rates whether complexed with myo
Ins(1,2,3)P3 or myo-InsP6. Iron accumulation from other compounds, notably D/L
myo-Ins(1,2,4,5)P4 and another inositol trisphosphate regio-isomer, D-myo
Ins(1,4,5)P3, was dramatically increased. Iron transport profiles from myo-InsP6
into mutants lacking the outer membrane porins oprF, oprD and oprP were similar
to the wild-type, indicating that these porins are not involved in the transport
process. The rates of reduction of iron (III) to iron (II) complexed to any of
the compounds by a Ps. aeruginosa cell lysate were similar, suggesting that a
reductive mechanism is not the rate-determining step.
PMID- 10196761
TI - Human ileostomy glycoproteins as a model for small intestinal mucus to
investigate adhesion of probiotics.
AB - Human ileostomy glycoproteins were used as a model for small intestinal mucus to
investigate the adhesion of 12 Lactobacillus strains, one Lactococcus strain and
one Propionibacterium strain, Both probiotic and dairy strains were tested.
Adhesive and non-adhesive Escherichia coli strains were used as controls. All the
strains were also tested for their adhesion to polystyrene. Adhesion to ileostomy
glycoproteins and to polystyrene varied significantly among the strains tested.
Lactobacillus rhamnosus (human isolate), Lactobacillus GG, Lact. acidophilus 1
and P. freudenreichii adhered to ileostomy glycoproteins. Adhesion was
concentration-dependent and the most adhesive strains were able to saturate the
substratum. These results indicate that human ileostomy glycoproteins can be used
as a model system to select potential probiotic strains to complement the
adhesion test with intestinal cell lines.
PMID- 10196762
TI - Antibiotic resistance of native and faecal bacteria isolated from rivers,
reservoirs and sewage treatment facilities in Victoria, south-eastern Australia.
AB - The incidence of resistance to ampicillin, chloramphenicol, kanamycin, nalidixic
acid, neomycin and streptomycin was significantly greater (P < 0.001) in native
heterotrophic bacteria than in Escherichia coli isolated from a range of sites
along the Yarra River in south-eastern Australia. There was no significant
difference in the incidence of resistance between native and faecal bacteria to
tetracycline. Both groups were almost totally resistant to penicillin.
Multivariate analyses indicated little clear spatial pattern in the incidence of
resistance in native bacteria from upstream vs downstream sites along the Yarra
River. In contrast, E. coli isolated from upstream (rural) sites tended to have a
lower incidence of resistance than isolates from downstream (urban) sites. These
findings have implications for the use of antibiotic resistance as a
bacteriological water quality parameter.
PMID- 10196763
TI - Use of pyrrolidonyl peptidase to distinguish Citrobacter from Salmonella.
AB - In the routine testing of foods for Salmonella, Citrobacter and other members of
the Enterobacteriaceae often produce colonies which are almost indistinguishable
from Salmonella on commonly used selective agars. Biochemical confirmation of
such colonies can be expensive and time-consuming. It has been suggested that the
enzyme pyrrolidonyl peptidase (PYRase) could be used as a rapid test to
distinguish Citrobacter colonies (PYRase-positive) from Salmonella (PYRase
negative). Pure cultures of Salmonella, Citrobacter and other Enterobacteriaceae
were tested for PYRase activity; all strains of Salmonella tested were PYRase
negative, and all Citrobacter tested were PYRase-positive. Inoculated and
naturally contaminated food samples were tested for the presence of Salmonella by
a standard cultural method. A PYR test was used to test Salmonella-like colonies
isolated on selective agar and potentially, eliminate PYR-positive isolates from
further biochemical testing. The test was able to screen out 6% of colonies
selected from samples inoculated with Salmonella, and 43% of colonies selected
from uninoculated samples.
PMID- 10196764
TI - Antiaflatoxigenic activity of eugenol is due to inhibition of lipid peroxidation.
AB - Eugenol inhibited aflatoxin production by Aspergillus parasiticus NRRL 2999 in a
dose-dependent manner up to a concentration of 0.75 mmol l-1 without inhibiting
growth. When the mould was grown for 3 d in the presence of 0.45 mmol l-1 eugenol
(concentration inhibiting aflatoxin production by 50%), in vivo activities of
components of polysubstrate monooxygenase were decreased at idiophase,
concomitant with decreased activities of enzymes involved in free radical
scavenging, lipid peroxidation and maintenance of redox potential. These results
indicate that antiaflatoxigenic actions of eugenol may be related to inhibition
of the ternary steps of aflatoxin biosynthesis involving lipid peroxidation and
oxygenation.
PMID- 10196765
TI - The effect of wind speed and direction on the distribution of sewage-associated
bacteria.
AB - A study of the relationship between wind and the distribution of sewage
associated bacteria was undertaken at a location where the sewage was discharged
into the sea adjacent to the mouth of a river. The numbers of presumptive
Escherichia coli were determined in 149 sea-water samples taken from three
locations at distances of 1.9, 2.4 and 4.3 km from the outfall. On each sampling
occasion, data on the wind speed and direction in the 3 h prior to collection of
the samples were also collected. Analysis of these data demonstrated a
significant role for wind speed and direction. With respect to wind direction,
the numbers of presumptive E. coli present in a sample were significantly higher
when the sample site lay downwind of the outfall. Wind speed was shown to have an
influence on the numbers of presumptive E. coli only when the sample site was
downwind of the outfall. In an analysis of 61 samples, an inverse correlation (r2
= 0.73) between salinity and log presumptive E. coli numbers was demonstrated.
These data demonstrate that wind speed and direction at the time of sampling
significantly influence the numbers of presumptive E. coli detected in any sea
water sample. It is argued that failure to pay sufficient attention to these
parameters in the design of monitoring programmes may result in the generation of
data that could provide a seriously distorted picture of the microbiological
status of a water body.
PMID- 10196766
TI - Nisin A depletes intracellular ATP and acts in bactericidal manner against
Mycobacterium smegmatis.
AB - Nisin is a bacteriocin produced by many strains of Lactococcus lactis. This study
examined the effect of nisin on Mycobacterium smegmatis, a non-pathogenic species
of Mycobacterium. Nisin had a minimum inhibitory concentration of 8.0 micrograms
ml-1 and a minimum inhibitory dose of 7.5 micrograms ml-1 against Myco.
smegmatis. Treatment with 25.0 micrograms ml-1 nisin caused partial inhibition of
Myco smegmatis; the survivors were nisin-sensitive when tested in a separate
experiment. Mycobacterium smegmatis cells exposed to 50.0 micrograms ml-1 of
nisin, lost their viability. the effect of nisin on the growth of Myco. smegmatis
was both time- and concentration-dependent. Nisin (10.0 micrograms ml-1) caused
97.7 +/- 2.0% reduction in internal ATP and leakage of intracellular ATP out of
Myco. smegmatis cells after several hours of treatment. These data suggest that
nisin inhibits Myco. smegmatis by the same mechanism by which it inhibits other
bacteria and warrants further investigation as a possible antitubercular agent.
PMID- 10196767
TI - Morphological changes of synchronized Campylobacter jejuni populations during
growth in single phase liquid culture.
AB - Campylobacter jejuni strains demonstrate a variety of growth phase-linked
distinct morphological forms when grown in liquid culture. The typical spiral
form of the organism, evident during logarithmic phase, undergoes elongation
during stationary phase before becoming coccoid via the formation of membrane
blebs and budded forms in decline phase. Cellular elongation and coccoid
formation occurred despite the inhibition of protein synthesis and without a
detectable change in the protein components of the inner and outer cell
membranes.
PMID- 10196768
TI - Actinorhodin production by Streptomyces coelicolor A3(2) in iron-restricted
media.
AB - Production of the polyketide antibiotic actinorhodin by Streptomyces coelicolor
A3(2) was investigated using a defined medium with or without iron
supplementation. Iron limitation was found to enhance the intracellular
production and export of the pigmented antibiotic. The effect of iron deficiency
was particularly pronounced when the bacterium was grown with nitrate instead of
ammonium. Analysis of the excreted pigment led to the identification of the
lactone form of actinorhodin, gamma-actinorhodin.
PMID- 10196770
TI - Assessment of microbial parameters as indicators of viral contamination of
aerosol from urban sewage treatment plants.
AB - In order to evaluate possible indicators of viral aerosol contamination in sewage
treatment plants, a year-long study was carried out on the relationships between
the presence of cytopathogenic viruses and the counts of total bacteria, faecal
streptococci and somatic coliphages in samples collected at various distances
from the aerosol source (aeration tank). The activated sludge plant studied
proved to be a significant source of microbe-bearing aerosol with high levels of
viral contamination. When the virus was found in sewage, it was also found in the
air, at least in the sites closest to the aeration tank. With regard to the
possibility of using the chosen parameters as markers of viral contamination, the
total bacteria and faecal streptococci counts were generally positively
correlated with viral presence, while coliphage counts yielded no analogous
relationship.
PMID- 10196771
TI - Growth of moulds inoculated into commercial mineral water.
AB - The growth of mould spores of Penicillium sp. and Cladosporium sp. inoculated in
a commercial mineral water product was studied. The strains had been isolated as
fungal foreign bodies in commercial mineral waters. In product A, which was not
originally sterilized and was contaminated with psychrophilic bacteria, the
inoculated mould spores of the strains did not grow; no increases in viable
colony counts or beta-glucans concentration in the samples were observed during
storage. In a sterilized product A, inoculated spores of the strains grew into
visible foreign bodies. The viable colony counts and the beta-glucans
concentration in the samples increased during storage. These results showed that
in a sterilized mineral water product, mould spores could grow into visible
foreign bodies.
PMID- 10196772
TI - Behaviour of Listeria monocytogenes under combined chilling processes.
AB - The behaviour of Listeria monocytogenes under chilling processes was
investigated. Growth kinetics were measured at 7 degrees C in TSBYE culture
medium as a function of pH (7.2 and 6.2), pre-incubation temperatures (4 or 7
degrees C), cooling (0.05 or 0.1 degree C min-1) and freezing (0 and -5 degrees
C) treatments. Growth curves generated were fitted by Gompertz and Baranyi
functions. The Baranyi function gave better parameter estimation values than the
Gompertz equation which over-estimated the specific growth rate values. Listeria
monocytogenes grew at 7 degrees C without a lag phase, except when the sub
culture was performed at 37 degrees C, whereas the specific growth rate was
affected by the chilling processes. In fact, L. monocytogenes grew slightly
faster at 7 degrees C when a 4 degrees C pre-incubation treatment was applied
than with a 7 degrees C pre-incubation treatment. These results suggest that to
mimic the processes of contamination in industry, predictive microbiology studies
with L. monocytogenes should be performed with organisms cultured at low
temperatures.
PMID- 10196773
TI - Detection of toxigenic strains of Bacillus cereus and other Bacillus spp. with an
improved cytotoxicity assay.
AB - An improved qualitative cell cytotoxicity assay for the detection of Bacillus
cereus emetic and enterotoxin is described. The presence of toxin in culture
supernatant fluids was detected by measurement with the tetrazolium salt MTT, as
it adversely affects the metabolic status of cultured CHO cells. Psychrotrophic
B. cereus isolates (65) were assessed for toxin production using the cytotoxicity
assay, and 91% of culture supernatant fluids were cytotoxic. Toxin assessment
using BCET-RPLA and ELISA immunoassays indicated that 51% and 85% of the
cultures, respectively, were toxigenic. There were pronounced strain differences
in the amount of toxin produced by the B. cereus isolates. Some isolates of B.
circulans, B. laterosporus/cereus, B. lentus, B. licheniformis, B. mycoides, B.
subtilis and B. thuringiensis were also toxigenic.
PMID- 10196774
TI - Biopreservation in modified atmosphere stored mungbean sprouts: the use of
vegetable-associated bacteriocinogenic lactic acid bacteria to control the growth
of Listeria monocytogenes.
AB - Two bacteriocinogenic strains of Pediococcus parvulus and one bacteriocinogenic
Enterococcus mundtii strain were evaluated for their potential to control the
growth of Listeria monocytogenes on refrigerated, modified atmosphere (MA) stored
mungbean sprouts. These three strains, which were isolated from minimally
processed vegetables, were shown to grow in culture broth at 4, 8, 15 and 30
degrees C. However, only Ent. mundtii was capable of bacteriocin production at 4
8 degrees C. Examination of the growth of these strains on agar under 1.5% O2 in
combination with 0, 5, 20 or 50% CO2 revealed significantly higher maximum
specific growth rates for Ent. mundtii than for Pediococcus parvulus at CO2
concentrations below 20%, which are relevant for MA-storage of vegetables.
Enterococcus mundtii was subsequently evaluated for its ability to control the
growth of L. monocytogenes on vegetable agar and fresh mungbean sprouts under
1.5% O2/20% CO2/78.5% N2 at 8 degrees C. The growth of L. monocytogenes was
inhibited by bacteriocinogenic Ent. mundtii on sterile vegetable-medium but not
on fresh produce. However, mundticin, the bacteriocin produced by Ent. mundtii,
was found to have potential as a biopreservative agent for MA-stored mungbean
sprouts when used in a washing step or a coating procedure.
PMID- 10196775
TI - Identification of a gene encoding an immuno-reactive membrane protein from
Campylobacter jejuni.
AB - A gene encoding a putative membrane protein has been identified from
Campylobacter jejuni NCTC 11168 following an immuno-screen of a lambda ZAP II
genomic DNA library with antiserum raised against glycine-extractable proteins.
The nucleotide sequence of the entire genomic insert revealed six open reading
frames, all but one of which have sequence homologues in the complete genome
sequence of Helicobacter pylori. The gene encoding the immuno-reactive protein
was further identified by independent expression of these reading frames in
Escherichia coli. The gene encodes an integral membrane protein, expression of
which in E. coli results in a profound filamentous phenotype.
PMID- 10196776
TI - Biodegradation of lindane (gamma-hexachlorocyclohexane) by the white-rot fungus
Trametes hirsutus.
AB - The ability of the white-rot fungus Trametes hirsutus to degrade an insecticide,
lindane, in liquid culture was investigated and compared with that of
Phanerochaete chrysosporium. Trametes hirsutus degraded lindane faster than P.
chrysosporium but the mechanism of degradation appears to be the same in both.
Two metabolites identified in both fungi were tetrachlorocyclohexane and
tetrachlorocyclohexanol. The presence of lindane alone inside the mycelium ruled
out the involvement of any intracellular enzyme(s) during the initial step of
lindane degradation. Lindane at a concentration of 0.27 mumol l-1 exhibited no
adverse effect on fungal growth.
PMID- 10196777
TI - Transmission of bovine TB in cattle: a critical reappraisal.
PMID- 10196778
TI - Concentration of metallothionein in mice livers after a small dose of
irradiation.
PMID- 10196779
TI - Specific radioactivity of europium-152 in roof tiles exposed to atomic bomb
radiation in Nagasaki.
AB - Specific radioactivities of residual europium (Eu)-152 were measured in six roof
tile samples exposed to the Nagasaki atomic bomb at two locations. The ground
distances of the two locations from the hypocenter are 1020 m and 1060 m. In
order to obtain reliable data, Eu-enriched samples (from 207 to 855 mg) were
prepared by separating Eu from each roof tile sample (from 1 to 2 kg). For the
major aliquot of the Eu-enriched sample, residual radioactivity of 152Eu was
measured using a low-energy photon spectrometer. For the minor aliquot of the Eu
enriched sample, Eu content was determined by neutron activation analysis.
Results of the specific radioactivity (152Eu/Eu, Bq mg-1) corrected to the time
of bombing were in a range from 0.080 to 0.446. Although the measured values
showed some scattering, they are moderately consistent with the calculated values
by the DS86 methodology, i.e. the average ratio of the calculated to measured
values is 1.3 +/- 0.8.
PMID- 10196780
TI - Protective roles of bacterioruberin and intracellular KCl in the resistance of
Halobacterium salinarium against DNA-damaging agents.
AB - Halobacterium salinarium, a member of the extremely halophilic archaebacteria,
contains a C50-carotenoid namely bacterioruberin. We have previously reported the
high resistance of this organism against the lethal actions of DNA-damaging
agents including ionizing radiation and ultraviolet light (UV). In this study, we
have examined whether bacterioruberin and the highly concentrated salts in this
bacterium play protective roles against the lethal actions of ionizing radiation,
UV, hydrogen peroxide, and mitomycin-C (MMC). The colourless mutant of H.
salinarium deficient in bacterioruberin was more sensitive than the red-pigmented
wild-type to all tested DNA-damaging agents except MMC. Circular dichroism (CD)
spectra of H. salinarium chromosomal DNA at various concentrations of KCl (0-3.5
M) were similar to that of B-DNA, indicating that no conformational changes
occurred as a result of high salt concentrations. However, DNA strand-breaks
induced by ionizing radiation were significantly reduced by the presence of
either bacterioruberin or concentrated KCl, presumably due to scavenging of free
radicals. These results suggest that bacterioruberin and intracellular KCl of H.
salinarium protect this organism against the lethal effects of oxidative DNA
damaging agents.
PMID- 10196781
TI - An improved system for selection of forward mutations in an Escherichia coli supF
gene carried by plasmids.
AB - An improved system to examine forward mutations that occurred in the supF gene of
Escherichia coli carried on a multicopy plasmid is described. The system was
validated by measuring spontaneous mutations of supF plasmids propagated in wild
type, recA- and mutM- mutY- E. coli strains, the mutation frequencies of which
were 1.3 x 10(-7), 6.3 x 10(-7) and 1.5 x 10(-6), respectively. Sequence analysis
of the supF mutant plasmids revealed that G:C-->T:A and G:C-->C:G transversions
dominated. This improved system allows rapid scoring and sequencing forward
mutations in the supF gene, thus permitting its use as a genetic target for
repair and mutagenesis studies in bacteria and mammalian cells.
PMID- 10196782
TI - Effects of X-ray irradiation on genomic DNA methylation levels in mouse tissues.
AB - Effects of ionizing radiation on the level of genomic DNA methylation in liver,
brain and spleen of mouse as well as in two kinds of cultured cells were examined
by high-performance liquid chromatography. Ten Gy of whole body X-radiation
reduced the 5-methyldeoxycytidine contents by about 40% within 8 hours after
irradiation in liver. Similar effects were observed at 4 or 7 Gy of X-ray
irradiation. However, no such change was detected in brain, spleen and cultured
cells. The data indicate that radiation-induced alteration in genomic DNA
methylation is not ubiquitous among different tissues and cells.
PMID- 10196783
TI - The effects of static magnetic fields and X-rays on instability of microsatellite
repetitive sequences.
AB - To determine the genetic effect of static magnetic fields (SMF), which are not
supposed to produce any significant DNA damage, we took advantage of DNA mismatch
repair (MMR) deficient cells, in which all the errors produced during DNA
replication are left uncorrected. We first established a simple and less labor
intensive method to analyze genetic changes in microsatellite repetitive
sequences in the MMR-deficient cells. After exposure to a strong SMF (6.34T) for
24 h, both MMR deficient HCT116 cells and proficient HeLa S3 cells did not
exhibit any significant effect on microsatellite changes. Moreover, when HCT116
cells were synchronized at the G1/S boundary by aphidicolin and exposed to SMF
during the whole S-phase, no increase in microsatellite changes was either
observed. In contrast, irradiation by a low dose X-ray (2Gy) significantly
increased microsatellite changes in HCT116 cells. This suggested that exposure to
strong SMF may not induce any significant level of genetic changes in
microsatellite sequences.
PMID- 10196784
TI - Bone classification: clinical-histomorphometric comparison.
AB - This study was aimed to correlate the hand clinical assessment of the bone
quality to the histologic structure quantified by histomorphometric evaluation of
bone density. Small bone biopsies were harvested in 56 patients during oral
implant surgery, and were utilized for histomorphometric evaluation. The bone
scoring was recorded during drilling of the implant bed, based on the hand-felt
perception of the drilling resistance. The bone biopsies were then processed to
obtain thin ground sections. The results of histomorphometric analysis were
expressed as percentage of bony trabeculae over the total biopsy area, and the
Spearman's rank correlation test, was applied to calculate the statistical
differences of the clinically assessed classes of bone density and linear
regression was calculated. Samples from the D1 showed a mean histomorphometric
density of 76.54% +/- 16.19. Samples from D2 showed a mean value of 66.78% +/-
15.82. D3 specimens had a mean histomorphometric density scoring 59.61% +/-
19.55%. D4 samples had a mean value of 28.28% +/- 12.02. The interclass
correlation analysis of the variance, showed that the clinically assessed classes
D1 (P = 0.01) and D4 (P = 0.0006) were significantly different from the
population. On the other hand, the classes D2 (P = 0.6) and D3 (P = 0.4) were not
significantly different. This study demonstrated that hand feeling allows to
distinguish, with statistically significant confidence, D1 and D4 bone, but
failed to distinguish between the intermediate classes of bone quality.
PMID- 10196785
TI - Immediate functional loading of Branemark dental implants. An 18-month clinical
follow-up study.
AB - A clinical and radiographical study was performed to compare the outcome of oral
rehabilitation in the edentulous mandible by fixed supraconstructions connected
to implants installed according to either i) a 1-stage surgical procedure and
immediate loading (Experimental Group-EG), or ii) the original 2-stage concept
(Reference Group-RG). The EG comprised 16 subjects with edentulous mandibles.
Beyond the non-smoking criteria the following specific inclusion criteria were
adopted: i) all patients had to consider themselves to be in good general health,
ii) the amount of bone had to enable the installation of 5-6, at least 10 mm long
fixtures to be bicortically anchored (Mk II fixtures; Nobel Biocare AB, Goteborg,
Sweden) between the mental foramina, and iii) the patients had to be available
for the follow-up and maintenance programme. A total of 88 implants were placed
in the EG (16 patients) compared to 30 in the RG (11 patients). In the EG, fixed
appliances were connected to the implants within 20 days following implant
installation while the fixed appliances in the RG were connected about 4 months
following fixture installation. At the time for delivery of the
supraconstructions all 27 patients were radiographically examined, an examination
that was repeated at the 18-month follow-up. The analysis of the radiographs from
the EG disclosed that during the 18-month observation period the mean loss of
bone support amounted to 0.4 mm. The corresponding value observed in the RG was
0.8 mm. During the 18-month observation period no fixture was lost in any of the
2 groups examined. The implants under study as well as those in the reference
material were at all observation intervals found to be clinically stable. The
present clinical study demonstrated that it is, at least based on an 18-month
observation period, possible to successfully load titanium dental implants
immediately following installation via a permanent fixed rigid cross-arch
supraconstruction. However, such a treatment approach has so far to be strictly
limited to the inter-foramina area of the edentulous mandible.
PMID- 10196786
TI - Guided bone regeneration with barrier membranes--a clinical and radiographic
follow-up study after 24 months.
AB - The present follow-up study evaluated clinical and radiographic parameters of
dental implants placed with simultaneous guided bone regeneration with expanded
polytetrafluoroethylene (e-PTFE) membranes. All implants were functioning well 24
months after insertion. In all, 63 patients with a total of 91 e-PTFE-augmented
implants were integrated in a regular maintenance protocol. Modified periodontal
data of 85 implants in 59 patients were recorded at 24 months and indicated no
difference to implants placed in sufficient pristine bone. The mean plaque score
(mplI) was 0.29, 74% of the sites showed no plaque. The sulcular probing depth
ranged from 1 to 7 mm with a mean of 2.6 mm (SD +/- 0.8). Of the sites 96.5% were
< or = 4 mm deep, in 49% of them probing resulted in bleeding. Periotest values 6
and 24 months (mean: -3.4 and -3.4) after placement revealed stable peri-implant
conditions and sustained osseointegration. The radiographic evaluation performed
6, 12 and 24 months post insertion yielded a mean bone loss of 0.93, 1.36 and
1.51 mm ranging from 0 to 4 mm. The short-term results of our clinical study
demonstrated stable peri-implant conditions 2 years after membrane-protected
osseous regeneration. The newly formed bone seemed to be able to withstand
functional loading in a predictable manner after 18 months.
PMID- 10196787
TI - Implant placement and simultaneous ridge augmentation using autogenous bone and a
micro titanium mesh: a prospective clinical study with 20 implants.
AB - This prospective clinical study evaluated bone regeneration around 20 dental
implants placed in 15 patients (mean age 39.7 years). Peri-implant bone defects
were augmented with autogenous bone grafts harvested intraorally from the
mandible (chin or retromolar area). Augmented sites were covered with an
individually trimmed micro titanium mesh which was rigidly affixed with
microscrews to the residual jaw bone. Height of implant exposure (mean 6.5 mm),
i.e. dehiscencies (80%) or fenestrations (20%), and graft height (mean 6.2 mm)
were measured in an apico-coronal direction using a periodontal probe. At re
entry (mean interval 6.6 months) the titanium mesh and microscrews were removed
and bone regeneration assessed. The mean height of the integrated bone graft was
5.8 mm corresponding to a mean bone fill of 93.5%. The overall postop healing
course was excellent with only one site developing a soft tissue dehiscence with
subsequent mesh exposure (complication rate 5%). This study demonstrated that a
micro titanium mesh in combination with autogenous bone grafts is effective for
treatment of peri-implant bone defects.
PMID- 10196788
TI - Blood supply to the maxillary sinus relevant to sinus floor elevation procedures.
AB - The maxillary blood supply is essential for preserving the vitality of the
affected maxillary region, integration of the grafting material, and wound
healing such as following sinus floor elevation. Although it is well established
that edentulous maxillae demonstrate a decreasing vascularity as bone resorption
progresses, the vascular conditions relevant to sinus floor elevation procedures
have not been investigated yet. This study deals with maxillary arteries relevant
to sinus floor elevation surgery and examines the vascularization of the lateral
maxilla after tooth loss. The vessels of the lateral maxilla of 18 maxillary
specimens (10 male, 8 female, mean age 67 years) were prepared anatomically and
the local main arteries, the number of macroscopically discernible branches and
anastomoses, their calibers, and the distance between the caudal main branches
and the alveolar ridge recorded. The lateral maxilla is supplied by branches of
the posterior superior alveolar artery (PSAA) and the infraorbital artery (IOA)
that form an anastomosis in the bony lateral antral wall, which also supplies the
Schneiderian membrane. This intraosseous anastomosis was found in all of the
specimens. Eight of 18 also showed an extraosseous anastomosis between PSAA and
IOA, vestibular to the antral wall, giving off an average of 3 branches cranially
and 5 branches caudally. The two anastomoses form a double arterial arcade to
supply the lateral antral wall and, partly, the alveolar process. The PSAA had a
mean caliber of 1.6 mm and exhibited an average of 2 endosseous and 1
extraosseous branches. The IOA had a mean diameter of 1.6 mm and showed an
average of 1 endosseous and 3 extraosseous branches. The mean distance between
the intraosseous anastomosis and the alveolar ridge was 19 mm in 2 defined
measuring sites. Its mean length was 44.6 mm. The epiperiosteal vestibular
anastomosis was situated further cranially at a mean distance of 23 to 26 mm from
the alveolar ridge and had a mean length of 46 mm. The rather large caliber of
the vessels supplying the lateral antral wall seems to be crucial to the fact
that the periosteal blood supply is maintained even in severe maxillary atrophy
and after complete disappearance of the centro-medullary vessels.
PMID- 10196789
TI - Evaluation of single-tooth restorations on ITI dental implants. A prospective
study of 29 patients.
AB - From January 1992 to March 1997, a total of 30 ITI hollow cylinder implants were
installed to replace lost single maxillary incisor teeth. Conical abutments with
cemented all-ceramic crowns were used in 10 cases and the Octa-abutment with
screw-retained metallo-ceramic crowns in 19 cases. One implant failed due to
postoperative infection, and was extracted a month after installation. After a
mean observation time of 3.4 years, the cumulative success rate is 96.7%. Only
minor bone loss has occurred around the implants, and there have been no other
complications to date. The implant system fulfills the requirements for good
function and esthetics.
PMID- 10196790
TI - Temperature increases during surface decontamination of titanium implants using
CO2 laser.
AB - The purpose of the present in vitro investigation was to measure temperature
changes at the implant surface when using pulsed CO2 laser in a simulated implant
surface decontamination protocol. Six threaded titanium implants were placed in a
fresh resected pig mandible. A 4 x 4 mm defect was created buccally to each
implant in order to expose the implant head and approximately 5 threads.
Temperature changes were monitored by two thermocouples placed near the
dehiscence and at the apical part of the implant. Several setting combinations of
the CO2 laser with regard to output power, pulse width, pulse repetition rate and
irradiation time were tested on dry and wet (distilled water) surfaces. Only
minor temperature increases were measured when lasing wet titanium surfaces,
while the temperature at dry surfaces exceeded the proposed thresholds for bone
damage at clinically relevant settings. It is concluded that the CO2 laser when
used on a wet implant surface in a pulsed mode at 8 W/10 ms/20 hz during 5 s
induces a temperature increase of less than 3 degrees C. This would minimize the
risk of temperature induced tissue damage as a result of lasing implant surfaces.
PMID- 10196791
TI - Guided bone regeneration using titanium grids: report of 10 cases.
AB - In order to ensure an adequate space where new bone can be formed in guided bone
regeneration (GBR), most surgeons fill bone defects with biomaterials. In this
work we evaluated new bone regeneration in 10 patients using only a blood clot
protected with titanium grids and non-resorbable membranes, without any filling
material. A manual measurement of the size of the bone defect, using a plastic
probe, was performed at 2 surgical steps. After 5 months of treatment, a biopsy
was taken from each patient, fixed and embedded in PMMA, examined
microradiographically and morphologically to evaluate the newly-formed bone. Our
results showed a good repair of the defects by bone regeneration (about 85%
overall), high mineral density of new bone around the implants after 5 months,
and steady state deposition processes. These results in GBR, without filling
material, appear very promising for implantology and reconstructive
odontostomatology practice.
PMID- 10196792
TI - Evaluation of restorative and implant alloys galvanically coupled to titanium.
AB - OBJECTIVES: As the success of implants leads to their increasing use in
restorative dentistry, attention should be devoted to the galvanic combination of
restorative materials with titanium. This paper used continuous corrosion
potential monitoring in conjunction with zero-resistance ammetry to obtain
galvanic corrosion properties of restorative and implant materials coupled with
titanium (ASTM F67-Grade II). METHODS: Direct coupling or galvanic experiments
were conducted on eight restorative and implant materials coupled to titanium.
Deaerated artificial saliva solution in a specifically designed corrosion cell
simulated an oral crevice situation. Open circuit potentials (Eo.c.) of each
material in the couple, coupled corrosion potentials (Ecouple corr), coupled
corrosion current density (lcouple corr) and the resultant charge transfer were
monitored. The results were analyzed using single factor ANOVA and Duncan's
multiple range tests. RESULTS: Noble restorative (Au-, Ag-, and Pd-based) alloys
coupled to titanium were found to be least susceptible to galvanic corrosion. Co
Cr-Mo, Ni-Cr and Fe-based alloys coupled to tatanium were found to be moderately
susceptible to galvanic corrosion due to mechanical-electrochemical interaction.
Ni-Cr-Be alloy coupled to titanium was found to be highly susceptible to galvanic
corrosion. The in vitro test results for the titanium/Disperalloy combination
does not concur with the published clinical performance of this combination, and
thus warrants further investigation. SIGNIFICANCE: From the data obtained in this
study and current literature profiles, acceptable restorative couples were
developed for use as clinical guidelines in restorative dentistry.
PMID- 10196793
TI - The effect of water contamination on dimensional change and corrosion properties
of a gallium alloy.
AB - OBJECTIVE: This aim of this study was to determine the effect of water
contamination on the dimensional change over time and the corrosion properties of
a gallium-based alloy (Galloy, SDI), compared to an amalgam (Tytin, Kerr).
METHODS: Normal and water-contaminated (10 microL of dH2O during condensation)
Galloy and Tytin samples were fabricated using a split metal mold and mechanical
condenser. The normal samples were tested for dimensional change under dry and
wet (immersed in dH2O) conditions. The water-contaminated samples were tested for
dimensional change under only dry conditions. Linear measurements were made over
a 7 day period using a stage-equipped dial micrometer. The corrosion potential
(Ecorr), the corrosion current density (lcorr), the passive current density (lp),
the protective scale formation current density (lps) and potential (Eps), and the
breakdown potential (Ebd) were obtained from the polarization curves generated in
oxygenated saline solution. Single factor ANOVA and Duncan's multiple range tests
were used to determine differences between the various samples. RESULTS: The
water-contaminated Galloy samples contracted to a minimum of -3.42 +/- 1.73
microns cm-1 in 5 h followed by expansion to a maximum of 22.56 +/- 3.90 microns
cm-1 at the end of 7 days. Normal Galloy and Tytin samples and water-contaminated
Tytin samples exhibited rapid contraction during the first 24 h, followed by
minimal change over the next 7 days. The Ecorr of normal and water-contaminated
Galloy samples was more active than that of the normal and water-contaminated
Tytin samples. The lcorr of the normal and water-contaminated Galloy samples was
three orders of magnitude greater than the lcorr of normal and water-contaminated
Tytin samples. The Eps for the water-contaminated Galloy and Tytin samples was
more noble than for the normal Galloy and Tytin samples. The Ebd for the Tytin
and water-contaminated Tytin samples was greater than the corresponding values
for the Galloy and water-contaminated Galloy samples. SIGNIFICANCE: The gallium
based alloy exhibited expansion if contaminated with water during the condensing
and setting process. Post-setting exposure to water did not result in expansion
of the gallium-based alloy. The alloy also exhibited a greater susceptibility to
corrosion than the amalgam. Due to the possibility of delayed expansion, this
material should be used cautiously, particularly in applications involving
weakened tooth structure.
PMID- 10196794
TI - Microhardness of in vitro caries inhibition zone adjacent to conventional and
resin-modified glass ionomer cements.
AB - OBJECTIVE: This study was conducted to correlate Knoop and triangular hardness
numbers by measuring the microhardness of in vitro caries-inhibited and
demineralized dentin adjacent to a conventional and two resin-modified glass
ionomer cements. METHODS: Box-shaped cavities were prepared on bovine root dentin
and restored with either Fuji II, Fuji II LC, or Vitremer. The teeth were then
decalcified in an acid buffered solution of 50 mmol l-1 acetic acid adjusted to
pH = 4.5 for 3 days. Knoop and triangular microhardness indentations were
performed perpendicular to the surface and parallel to the cavity wall, in the
demineralized lesion and inhibition zone. Calcium and phosphorous contents of the
outer lesions and inhibition zones were compared using energy-dispersive X-ray
spectrometry (EDS). The correlation between Knoop and triangular hardness was
analyzed by correlation coefficient. The statistical significance of hardness
data was analyzed by one-way ANOVA and Fisher's PLSD test (p < 0.05). RESULTS:
Triangular hardness (HT) correlated well with Knoop hardness number (KHN) (r2 =
0.81, p < 0.05). The microhardness of the inhibition zone created by Fuji II was
of 59.2 +/- 3.8 HT and was statistically significantly higher than the zone
produced by Fuji II LC and Vitremer. Fuji II LC and Vitremer produced inhibition
zones with similar microhardness [48.3 +/- 3.5 HT and 44.0 +/- 7.6 HT,
respectively (p > 0.05)]. Calcium and Phosphorous were present in the inhibition
zone, but did not exist in the demineralized lesion. SIGNIFICANCE: Knoop and
triangular hardness numbers correlated significantly (p < 0.05), and the latter
seems to be a promising alternative method for measuring very narrow surfaces.
Despite the fact that all glass ionomer materials used in this study were
effective in producing an acid-resistant layer, microhardness and intensity of
these layers were material dependent.
PMID- 10196795
TI - Polishing and coating of dental ceramic materials with 308 nm XeCl excimer laser
radiation.
AB - OBJECTIVES: The polishing and coating of ceramic surfaces is recommended in order
to improve the physical properties of dental ceramics. Conventional methods for
the surface treatment of dental ceramic materials are not capable of creating a
smooth surface without microcracks. The special radiation characteristics of XeCl
excimer laser light indicate that it must be possible to treat ceramic surfaces
in order to produce a polished finish. The aim of this study was to investigate
the efficacy of XeCl excimer laser radiation for the polishing and coating of
dental ceramics. METHODS: Samples (n = 64) of four different dental ceramic
materials were irradiated with 308 nm XeCl excimer laser radiation at varying
energy densities per laser pulse of 1.57, 3.14, and 6.28 J cm-2. In detail, the
subjects for irradiation were samples of Ivoclar-Empress (leucite-reinforced
feldspathic ceramic), In-Ceram Spinell (double crystalline spinell ceramic), In
Ceram Alumina (alumina oxide; continous interpenetrating phase composite ceramic)
and Vita-Mark II (feldspathic ceramic). The roughness (Ra) of the laser-treated
ceramic surfaces was measured using a profilometer. In addition, SEM and AFM
investigations of the changes in surface structure were conducted. The changes in
surface roughness due to laser treatment were analyzed for their statistical
significance using ANOVA with the Scheffe test at a level of significance of
0.05% (p < 0.05). Depending on the type of ceramic material and the energy
density of the radiation, varying reductions of the surface roughness were
obtained. In general, minimum values of the roughness were measured on samples
irradiated with maximum energy density of radiation. RESULTS: The lowest
roughness value was obtained for the specimen of In-Ceram Spinell: 1.30 (+/-
0.19) microns. The mean value for minimal roughness of Ivoclar-Empress was 1.92
(+/- 0.35) microns, that for In-Ceram Alumina was 2.04 (+/- 0.49) microns, and
that for Vita-Mark II was 2.72 (+/- 0.40) microns. Ultrastructural examination of
laser-treated ceramics in part demonstrated both extensive fusion and
inhomogeneous surfaces with blistering and the formation of microcracks.
SIGNIFICANCE: It is concluded that the physical roughness of dental ceramic
surfaces can be significantly reduced by 308 nm excimer laser irradiation.
Nevertheless, the laser-treated surface was in no case completely fused and the
formation of microcracks and blistering was observed. Therefore, after using an
XeCl excimer laser for finishing dental ceramic alloys, further polishing of the
laser-treated ceramic surfaces will be needed.
PMID- 10196796
TI - Microtensile testing of dentin adhesives.
AB - OBJECTIVES: This study was conducted in order to compare the microtensile and
shear bond strengths of five commercial dentin adhesive systems. Scotchbond
Multipurpose with maleic acid (SM), Scotchbond Multipurpose with phosphoric acid
(SP), Scotchbond Multipurpose Plus (SBP), Clearfil Liner Bond System (CL), and
Prime and Bond (PB) were tested. METHODS: Thirty extracted unerupted third
molars, in groups of six teeth per adhesive system, were prepared for
microtensile testing. The specimens were tested following a 24 h incubation at 37
degrees C in normal saline. Shear bond testing was performed on 35 additional
teeth, using seven teeth per adhesive system. After testing, the fracture sites
were observed using light microscopy and a scanning electron microscope to
determine the type of failure involved. RESULTS: The microtensile test results
(mean +/- SD) were SM, 24.6 +/- 7.2 MPa; SP, 28.8 +/- 11.8 MPa; SBP, 22.7 +/- 6.5
MPa; PB, 25.5 +/- 9.4 MPa; and CL, 36.8 +/- 10.0 MPa. A Bonferroni post-hoc test
showed significantly (p < 0.05) greater strength for CL compared to SM, SP, SBP,
and PB. The shear bond strength test results were SM, 19.4 +/- 4.4 MPa; SP, 24.5
+/- 8.4 MPa; SBP, 15.3 +/- 4.9 MPa; PB, 23.2 +/- 7.1 MPa; and CL, 24.8 +/- 3.5
MPa. No statistically significant differences were found among the shear bond
strength test results. The shear bond test produced significantly more failures
within dentin and composite than the microtensile method. SIGNIFICANCE: It is
concluded that the microtensile test produced a more definitive assessment of
adhesive bond strength than the shear bond test. Microtensile testing showed CL
to be significantly stronger than SM, SP, SBP, and PB (p < 0.05).
PMID- 10196797
TI - Stress induced phase transformation of a cesium stabilized leucite porcelain and
associated properties.
AB - OBJECTIVES: The addition of CS2O to dental porcelains might provide a means for
controlling the thermal expansion and toughness of feldspathic porcelains. The
purpose of this investigation was to determine for a leucite porcelain the effect
of CS2O content upon its coefficient of thermal expansion (alpha), toughness,
hardness, and content of low (tetragonal) leucite and high (cubic) leucite.
METHODS: In order to determine the amount of low leucite in the specimens, an x
ray calibration curve for low leucite and an internal standard of copper was
obtained using quantitative x-ray diffraction techniques. Utilizing a stress
induced phase transformation between low and high leucite, an x-ray intensity
conversion ratio (r) was determined for high leucite so that the calibration
curve for low leucite could be used to determine the amount of high leucite
present in the experimental porcelains. Specimens were prepared with various
amounts of CS2O (0.0, 0.5, 1.0, 1.5, 2.0 mol%) so that, except for the as
received porcelain (A), all had the same thermal history. Specimens were tested
for content of low and high leucite, hardness (Vickers), toughness (indentation
strength method), and coefficient of thermal expansion (alpha) over two
temperature ranges (30-500 degrees C and 30-640 degrees C). Fractured surfaces
were examined with a scanning electron microscope (SEM). For each property,
specimen groups were compared for statistical differences. These comparisons were
statistically analyzed using analysis of variance (ANOVA) and Fisher's protected
least significant differences (PLSD). RESULTS: Quantitative x-ray examination of
abraded and heat-treated specimens demonstrated that a stress induced phase
transformation occurred which could be reversed by heat treatment. The conversion
ratio was determined as r = 1.93 +/- 0.29. The addition of CS2O lowered the wt%
of low leucite from 63 +/- 6% to 0% and increased the amount of high leucite from
0% to 62 +/- 5%. ANOVA showed that the addition of CS2O had a significant effect
on alpha (p < 0.0001), hardness (p < 0.005), and toughness (p < 0.0001). CS2O
significantly (PLSD) lowered the alpha (p < 0.0001), hardness (p < 0.01), and
toughness (p < 0.0001) of a high-content leucite porcelain. SIGNIFICANCE: A
stress induced phase transformation of high leucite to low leucite was
demonstrated and, as a consequence, suggested the potential for phase
transformation toughening. The alpha of a leucite porcelain could be controlled
by stabilizing high (cubic) leucite to room temperature with the fraction of high
leucite dependent upon the amount of CS2O added. A method was developed to
determine the amount of high leucite present in a porcelain.
PMID- 10196798
TI - The influence of cross-sectional shape and surface area on the microtensile bond
test.
AB - OBJECTIVES: The purpose of this study was to determine the effect of the cross
sectional area shape (cylindrical vs. rectangular) and the bonding surface area
on the microtensile bond strengths and stress distribution of four dentin
adhesive systems (Scotchbond MP Plus, OptiBond FL, OptiBond Solo, One-Step). In
addition, finite element analysis (FEA) models were developed to investigate
stress distributions. METHODS: Extracted human molars were cut vertically and the
occlusal enamel removed; one-half of the tooth was used for rectangular
specimens, the other half for cylindrical specimens. The occlusal dentin was
bonded according to the manufacturers' directions and covered with a block of
resin composite. For the cylindrical specimens, the bonded dentin was shaped with
a diamond bur on a lathe to produce specimens of area 1.1, 1.5 or 3.1 mm2 at the
bonded interface. The rectangular specimens were sectioned to obtain bar-shaped
specimens, which were shaped to produce hour-glass shaped specimens with the same
area as the round specimens. Bonds were stressed in tension at a speed of 1 mm
min-1. The mean bond strengths were compared using two-way ANOVA, one-way ANOVA,
LSD and Student's t tests. The fractured surfaces were examined by scanning
electron microscopy, and the frequencies of the fracture modes were compared
using the Kruskal-Wallis and Mann-Whitney U tests. FEA models were created
simulating the cross-sectional areas for bonding to determine the stress
distribution. RESULTS: The 3.1 mm2 bonding area groups showed significantly lower
bond strengths than the 1.1 mm2 bonding area groups (p < 0.05), except for the
rectangular specimens using Scotchbond MP Plus and One-Step. Most cylindrical
specimens of bonding area 1.1 or 1.5 mm2 exhibited adhesive failure at the
interface between the dentin and the adhesive resin. No differences were
determined between cylindrical and rectangular specimens. The fracture mode
matched the stress distribution patterns calculated from the FEA modeling.
SIGNIFICANCE: The results indicate that the test methods using small surface
areas produce higher bond strengths than those using larger surface areas, and
that cross-sectional shape has little effect. This is probably a result of fewer
defects occurring in the small-area specimens.
PMID- 10196800
TI - Ethics and the three faces of statistics.
PMID- 10196799
TI - Effects of acid-etching on the tensile properties of demineralized dentin matrix.
AB - OBJECTIVES: Little research has been done to evaluate the effects of acids
commonly used in adhesive dentistry, on the tensile properties of the
demineralized dentin matrix. The purpose of this study was to evaluate the
effects of a number of acidic conditioners on the ultimate tensile strength (UTS)
and modulus of elasticity (E) of human coronal dentin matrix. METHODS: Small hour
glass shaped (for UTS) or l-beam shaped (for determination of E) were prepared
from mid-coronal dentin of extracted human third molars. After protecting the
ends with varnish, the middle of the specimens was completely demineralized in
0.5 M EDTA (pH 7). UTS was determined by tensile stressing to failure. Modulus of
elasticity was calculated from stress strain curves. The results were analyzed by
ANOVA and Student-Neuman-Keuls test at the 95% confidence level. RESULTS: Brief
(ca. 1-2 min) exposure of demineralized dentin matrix to acids had no measurable
effects on its tensile properties. Ten-minute exposures to 2.5% and 17.5% nitric
acid lowered (p < 0.05) the UTS compared to phosphate buffered saline (PBS)
exposed controls. Exposure of the decalcified dentin to 10% citric acid
containing 3% ferric chloride, 10% citric acid, 37% phosphoric acid or 17.5%
nitric acid containing 3% ferric chloride for 10 min had no effect on UTS. None
of these acids consistently lowered stiffness. SIGNIFICANCE: The results indicate
that relatively long exposures to acids are required to alter the tensile
properties of demineralized dentin. It is unlikely that the brief exposures to
acids that are used in adhesive dentistry would acutely weaken the physical
properties of demineralized dentin. However, long-term studies should be done to
determine if such treatment increases the susceptibility of the matrix to
hydrolysis.
PMID- 10196801
TI - Implants--now is the time.
PMID- 10196802
TI - Loss of crestal bone around dental implants: a retrospective study.
AB - The loss of crestal bone associated with dental implants is a significant
clinical phenomenon. The occurrence of such bone loss will often compromise long
term prognosis and, if extensive, ultimately lead to failure. Relatively few
studies have focused on the reasons for loss of crestal-supporting bone around
implants, although numerous explanations for the phenomenon have been proposed.
This retrospective investigation examines one potential causative factor for
implant-associated crestal bone loss, which has only recently received attention,
i.e., location of the implant/transmucosal abutment interface (ITAI) relative to
the crestal bone. A retrospective clinical evaluation of 350 individual implants
in 255 patients indicates a direct relationship between subgingival placement of
the ITAI and loss of crestal supporting bone. In addition, scanning electron
microscopic examination of 45 failed implants showed significant plaque
accumulation at the ITAI, the transmucosal abutment/prosthesis interface (TAPI),
and the interface between the implant smooth collar and subjacent plasma-spray
coated surface.
PMID- 10196803
TI - Bone structure, metabolism, and physiology: its impact on dental implantology.
AB - When placing implants in the mandible or maxilla, it is important for clinicians
to understand the process of bone remodeling, the different types of bone, and
how these factors can affect the integration of osseous dental implants.
Approximately 0.7% of a human skeleton is resorbed daily and replaced by new
healthy bone. With aging and metabolic disease states, the normal turnover
process may be reduced, resulting in an increase in the mean age of the present
bone. This increase can affect the placement and integration of implants. Herein
follows a discussion of different types of bone cells, the metabolism of bone,
the microscopic, macroscopic, and molecular structure of bone, and the process of
bone modeling and remodeling.
PMID- 10196804
TI - Reduction of implant loading with therapeutic biomechanics.
AB - All physiologic biomechanical processes are interrelated and, therefore,
reactive, which produces an accumulative effect that can cause implant overload.
A new approach called "therapeutic biomechanics" suggests using corrective
procedures to reduce implant loading. The head of the implant is positioned as
close to the midline of the restoration as possible. Implant inclination may be
required, but it produces less torque (moment) than horizontal implant offset.
Posterior cross occlusion should be used where possible to decrease horizontal
implant offset. Angulated, or reangulated abutments provide access or parallelism
as needed. The posterior cusp inclination should be markedly reduced. When a
vertical overlap is present anteriorly, a horizontal stop on the maxillary
lingual surface redirects harmful lateral force to be vertical toward the implant
and supporting bone. Because of physiologic variability, creating a modified
centric occlusion that contains a 1.5-mm fossa will produce vertical resultant
force within this range of motion rather than lateral force.
PMID- 10196805
TI - Five-year 224-patient prospective histological study of clinical applications
using a synthetic bone alloplast.
AB - Clinical and histologic evaluations of a synthetic bone were performed in 224
patients in a well monitored environment. This material (Bioplant HTR, Bioplant
Inc., South Norwalk, CT) was used to obliterate cysts, treat periodontal defects,
correct jawbone contours and deficiencies, and gain sufficient support for the
placement of dental implants in maxillary subantral augmentation. Implants were
positioned either at the time of the synthetic bone graft or after the new
supporting tissue was formed. Evidence of new bone formation between the
synthetic granules and host tissue was observed during histological examinations.
After the material was placed, tissue that could strengthen and augment the
inferior wall of the maxillary sinus formed in 3 months. This was observed both
clinically and radiographically. After 8 to 12 months, this tissue provided
sufficient hard tissue support for the placement of dental implants. This
clinical study reconfirmed the applicability of a synthetic bone for bone
replacement and augmentation in oral and maxillofacial surgery. No complications
caused by infection, inflammation, or rejection of the implanted graft material
were observed.
PMID- 10196806
TI - Introduction: surface and coating variability on implanted biomaterials.
PMID- 10196807
TI - Overview of surface variability of metallic endosseous dental implants: textured
and porous surface-structured designs.
AB - A variety of successful endosseous dental implants with different surface forms
are currently available for clinical use. These all achieve implant-to-bone
fixation primarily (if not totally) through mechanical interlock of bone with
implant surface features introduced by design or chance during implant
fabrication. Equally important to establishment of rigid fixation is the rate at
which it is achieved, because faster rates allow earlier implant loading and less
chance of inadvertent early loading that might prevent implant
"osseointegration." Investigations of surface modification to favorably affect
osteoconductivity and bone bonding represent an active area of research in the
field of dental implant development. This article presents a review of available
surface designs and future research directions for improved devices.
PMID- 10196808
TI - Current status of ceramic coatings for dental implants.
AB - There are various ceramic coatings available for dental implants. From a
commercial standpoint, plasma-sprayed hydroxyapatite (HA) is the most popular.
These coatings are typically partially amorphous after processing and contain
crystalline phases other than HA. Plasma-sprayed HA and the other bioactive
ceramic coating materials have been shown to enhance bone apposition as compared
with uncoated metal implants. Some of the other available materials include the
bioglasses, other calcium phosphates such as fluorapatite and tricalcium
phosphate, and the inert ceramics such as alumina. The plasma-spray process is
not optimum for all types of ceramic coatings, because it is not suitable for
coating porous surfaces; the exact control of structure and chemistry is
difficult with this process, and bond strength is not as high as is desired for
some applications. Alternative methods for coating include sol-gel processing,
ion beam and radio frequency (RF) sputtering, pulsed laser deposition, hot
isostatic pressing, and electrophoretic deposition. The use of osteoinductive
agents in conjunction with ceramic-coated implants is of current interest, and
the degree and type of bonding of these agents appear to vary with the
composition of the ceramic coating. Because there seems to be no satisfactory
means of incorporating osteoinductive agents into ceramic coatings during any of
the conventional coating procedures, the best approach seems to be to diffuse the
agents into the coating after processing. Other possibilities include the
tethering of the agents to the surface of the ceramic by suitable organic
molecules or the placing of the agent in some carrier material such as a cement,
which is placed around the implants.
PMID- 10196809
TI - Dissolution kinetics of calcium phosphate coatings.
AB - Plasma spray and high velocity oxy-fuel (HVOF) techniques produce coatings with
varying composition and amounts of amorphous and crystalline phases. For coatings
containing greater amorphous phases, a higher release of calcium ions is evident
when samples are placed in Hank's calcium-free balanced salt solutions. Calcium
is released from the amorphous phases in the coating, a conclusion that is
supported by x-ray powder diffraction (XRD) results. Ion beam sputtering and RF
magnetron sputtering under lower energy conditions produce amorphous coatings
that will dissolve in a very short time period. When heat treated, crystalline
phases are produced in the coatings. Heat-treated coatings are significantly more
stable than the amorphous coatings. The dissolution rates of both amorphous and
crystalline coatings produced by RF magnetron sputtering have been measured under
constant solution conditions at pH 6.50. No reprecipitation is possible under
these conditions. The amorphous coating dissolved at a significantly higher rate
than the heat-treated coating. Reprecipitation of calcium phosphate onto
amorphous coatings is possible in a physiological pH solution. Under these
conditions, the dissolution rate of the amorphous coating is four times slower
than at the pH 6.50 conditions.
PMID- 10196810
TI - Tissue compatibility to different surfaces of dental implants: in vitro studies.
AB - Factors affecting cell and tissue responses to dental implant biomaterials are
typically characterized as spatial and temporal. Spatially, a dental implant must
form an interface with both bone tissue for the development and maintenance of
biomechanical stability and soft tissue for the prevention of microbial infection
that can lead to peri-implantitis. There is a developing body of knowledge
regarding the reactions of host tissues to implant materials, although the
specific mechanisms by which these responses are not yet totally understood. From
a temporal standpoint, there seems to be a sequence of events after placement of
an implant that involves cell attachment, migration, and differentiation. These
early wound healing responses appear to be influenced significantly by the
properties of the underlying implant surface. Our laboratory has focused its
attention on the first cellular event, i.e., cell attachment at the interface
between bone and the implant surface. An in vitro primary cell model has been
developed and used to study the influence of materials selection (Ti, Ti-6Al-4V,
hydroxyapatite-like coatings), surface topography (smooth to rough), and surface
chemistry (as a function of preparation treatments) on the cellular events that
occur at implant surfaces. Currently, we believe that both uncoated Ti implants
and those fabricated with calcium phosphate or hydroxyapatite-like coatings are
capable of supporting initial cellular attachment, although they probably occur
by different and incompletely understood mechanisms. The initial interactions of
the host tissues with the implant surface remain key for long-term acceptance and
must be understood if new generations of tissue engineered devices are to be
developed and used clinically.
PMID- 10196811
TI - In vivo evaluation of the biocompatibility of implanted biomaterials: morphology
of the implant-tissue interactions.
AB - Electron microscopic observations were made from tissues apposing titanium and
ceramic root form and blade implants. The tissue was serially sectioned from the
most coronal epithelium, through the gingival connective tissue, to the osseous
support tissues, and directly to the most apical tissue support. Of the thousands
of sections analyzed for each implant, 500 micrographs were routinely viewed for
each of the implants analyzed by this study. Of the 120 total implants placed in
30 adult dogs, 60 were used for electron microscopy. Osseointegrated implants
were often apposed by a mineralized matrix of collagenous fibers. The dense
mineralized collagen matrix was often separated from the implant by only a
ruthenium positive electron dense deposit 20 to 50 nanometers thick. Areas of the
same implant were also apposed by an unmineralized collagen fiber stroma, which
ranged in thickness, that contained osteoblasts. Interaction of the osteoblasts
and the unmineralized collagen fibers resulted in the mineralization events of
osteogenesis. Also apposing other areas of the same integrated implants were
lacunar areas containing osteoclasts and vessels. These zones were similar to
Howship's Lacunae. These results demonstrated that a normal homeostasis of
catabolic osteoclastic activity and metabolic osteoblastic activity resulted in a
dynamic implant-tissue interface. This biocompatible and dynamic support complex
provides a construct for the long-term clinical serviceability of osseointegrated
implants.
PMID- 10196812
TI - Unanticipated outcomes: dental implants.
AB - Dental surgical implant treatment modalities continue to be relatively successful
within musculoskeletal restorative systems. Because available systems include a
wide range of metallic and ceramic biomaterials plus multiple designs for the
implant body, transgingival abutment, and intraoral crown constructs, failure
analyses of explanted devices must include comprehensive information. The current
opinions are based on approximately 4000 musculoskeletal implant device studies
conducted from 1970 to 1997. As a subset, the dental systems with and without
calcium phosphate ceramic on the endosteal portion of the implants will be
considered at 0 to 1, 1 to 5, 5 to 10, and beyond 10 years in vivo. Observations
will be reported and opinions provided about the advantages and disadvantages of
ceramic coated implant systems.
PMID- 10196813
TI - Guidelines for analysis and redesign of dental implants.
AB - This article describes the simulation of the mechanical behavior of two types of
endosseous-threaded dental implants and the development of design guidelines for
such implants. Two- and three-dimensional representations, static and dynamic
cyclic loads, different material models, axial loads, and loads directed at the
occlusal angle are all used. A novel model of trabecular bone is used to
incorporate fatigue effects. Directional material behavior, progressive bone
loss, and partial osseointegration are also modeled. Bone support using muscle
attachment is modeled using spring constraints as opposed to fixed constraints
used in previous studies. The tapered thread design from Branemark Inc. exhibited
higher stress levels in bone than those observed in the parallel profile thread
from BUD Medical Devices, Inc. The BUD implant distributes stresses more evenly.
Studies examining 25%, 75%, and 100% osseointegration showed cortical bone
carried most of the load with resulting overload leading to crestal bone loss.
Plots of stress showed that with increasing crestal bone loss, the majority of
the load was transferred directly to the weaker trabecular bone tissue. Finally,
it was shown that with proper implant redesign, loads can be transferred more
evenly to the implant. This also improves fatigue life of the bone.
PMID- 10196814
TI - Correcting vertically altered faces: orthodontics and orthognathic surgery.
AB - Traditional methods of model and cephalometric examination are often unreliable
for diagnosis and treatment planning. This article presents soft tissue
cephalometric analysis that measures the face, analyzes important dentoskeletal
structures that determine facial appearance, and reveals the etiology of
malocclusions. A technique for cephalometric treatment planning for guiding
esthetic facial changes and the method of occlusal correction are also described.
Vertical maxillary excess and vertical maxillary deficiency malocclusions are
used to illustrate these techniques.
PMID- 10196815
TI - Morphologic analysis of dentofacial structure in patients with acromegaly.
AB - The purpose of this study was to investigate the morphologic changes of the oral
and maxillofacial skeletal structure in patients with acromegaly and the
correlation between growth hormone, age at onset, and duration. Fifty-four
acromegalic patients (28 men and 26 women) were compared with 45 normal adults
(23 men and 22 women) using casts and cephalometric analysis. The incisor
relationship was classified into four types: edge-to-edge bite, crossbite,
maxillary incisor protrusion, and normal bite. Many cases of edge-to-edge bite
and crossbite were observed in acromegalic patients. The most characteristic
craniofacial skeletal differences in patients with acromegaly were protruded
glabella and increased anterior face height. Enlargement of the ascending ramus
and prominence of the mandible, chin, and mouth were the most noticeable profile
characteristics of acromegalic patients. Male patients tended to demonstrate
downward mandibular advancement and crossbite, while females showed extension of
the ascending ramus, downward displacement of mandible, bimaxillary alveolar
protrusion, and edge-to-edge bite.
PMID- 10196816
TI - Anterior-inferior mandibular osteotomy in treatment of obstructive sleep apnea
syndrome.
AB - In a prospective randomized study on treatment of obstructive sleep apnea
syndrome, anterior-inferior mandibular osteotomy with the purpose of stretching
the suprahyoidal muscle was performed as one of the treatment methods. Ten men
aged 20 to 65 years, without cardiovascular or neurologic disease, with normal
maxillomandibular relation, and having an apnea index between 5 and 25 were
included in the study. After a specially designed osteotomy of the chin, the
anterior suprahyoidal muscles were detached, stretched approximately 10 to 12 mm,
and sutured. The chin was then placed in its original position and post-operative
evaluation was performed. Although there were initial reports of decreased
daytime sleepiness and less snoring after surgery, the results after 12 months
were discouraging. Somnographic registration (apnea index, apnea/hypopnea index,
and oxygen desaturation index) as well as cephalometric analysis failed to show
positive results. Hence, suspension of the suprahyoidal muscles as a method of
treatment for obstructive sleep apnea syndrome cannot be recommended.
PMID- 10196817
TI - Morphologic changes in the upper airway structure following surgical correction
of mandibular prognathism.
AB - The purpose of this study was to investigate morphologic changes in oropharyngeal
structures in mandibular prognathic patients after orthognathic surgery. The
study consisted of 25 patients (12 males and 13 females) with mandibular
prognathism who underwent surgical and orthodontic treatment. A set of 4
standardized lateral cephalograms were obtained from each subject preoperatively
and at 3 months, 6 months, and 1 year postoperatively. Morphologic changes in
upper airway structures were evaluated longitudinally by gender. Parameters of
the anteroposterior width of the pharynx significantly decreased at 3 and 6
months in both genders, and these parameters tended to rebound to the
preoperative values 1 year postoperatively in females, but not in males. The
hyoid bone significantly descended inferiorly 1 year postoperatively in males,
while there were no significant changes in females. The distance between the
hyoid bone and the third vertebra gradually decreased in males postoperatively;
however, there were no significant changes in females. The cross-sectional area
of the hypopharynx significantly decreased 1 year postoperatively in males, but
not in females. These results indicate that the upper airway morphology changed
differently in males and females following surgery. To compensate for skeletal
changes following surgery, it appears that males and females responded in
different ways to preserve a functional upper airway.
PMID- 10196818
TI - Surgical manipulation of the occlusal plane: new concepts in geometry.
AB - Rotation of the maxillomandibular complex and the consequent alteration of the
occlusal plane angulation to improve functional and esthetic results have been
well documented. The decision to change the occlusal plane angulation cannot be
arbitrary and is made only when desired results cannot be obtained by
conventional treatment planning. The geometry of rotation should be accurately
planned by establishing a specific point around which the maxillomandibular
complex should be rotated to achieve specific esthetic results. Treatment
planning using anterior nasal spine and maxillary incisor tip as rotation points
has been described and results demonstrated. This article will introduce
additional points of rotation that may be considered based on a triangle
constructed during treatment planning. Two clinical examples are presented in
which these types of rotation were implemented.
PMID- 10196819
TI - Stability after Le Fort I osteotomy in cleft lip and palate patients.
AB - Le Fort I osteotomies were performed in 20 patients with cleft lip and palate as
a one-segment movement, and the fragments were fixed with miniplates without bone
grafting. Tracings of preoperative and serial postoperative lateral cephalograms
were used to determine changes in maxillary position. The posterior nasal spine,
not subjected to extensive changes during surgical procedures and remodeling, was
found to be the most reliable landmark for measuring maxillary advancement and
stability. The mean maxillary advancement was 5.96 mm. Analysis did not reveal
significant changes in linear and angular measurements from immediately
postoperative to 6 months postoperative. A modest maxillary advancement by Le
Fort I osteotomy, along with alleviation of palatal scar tissue tension and
miniplate fixation, is a stable surgical method in patients with cleft lip and
palate.
PMID- 10196820
TI - Orthodontic fixation of mandibular fracture: a case report.
AB - The present case illustrates a nonsurgical method of fixing a minimally displaced
mandibular fracture with use of an easily prepared orthodontic appliance. This
method offers several advantages for both the attending staff and the patient.
PMID- 10196821
TI - Correction of posttraumatic maxillary deficiency by anterolateral alveolar
osteotomy.
AB - Anterolateral alveolar osteotomy was performed in a patient who experienced
facial trauma in a traffic accident. Bony sequela had remained in the maxilla
after the emergency surgery, affecting the facial appearance. A different
technique of osteotomy for this unusual type of deformity is presented.
PMID- 10196822
TI - Prosthodontics looks to the future.
PMID- 10196823
TI - The esthetics of the smile: a review of some recent studies.
AB - PURPOSE: This article reviews recent research on the esthetics of the smile,
covering the attractiveness of the smile, the effect of aging on the smile, oral
condition and the smile, personality and smile, and smile exercises. MATERIAL AND
METHODS: The subjects were Koreans with normal occlusion. Photographs of a full
smile were taken and the esthetic quality of the subjects' smiles was estimated.
Smile scores were correlated with oral condition, personality, the practice of
smile exercises, and elements of the smile, such as the position of the lip in a
smile. The personality of the subjects was assessed by means of a Sixteen
Personality Factor Questionnaire. Gibson's smile exercises were used to
investigate the effect of smile exercise. RESULTS: In an attractive smile, the
full shape of the maxillary anterior teeth was shown between the upper and lower
lip, the upper lip curved upward or was straight, the maxillary anterior incisal
curve was parallel to the lower lip, and teeth were displayed to the first molar.
The amount of maxillary incisal exposure gradually decreased with age,
accompanied by a gradual increase in mandibular incisal exposure. Personality
traits such as warmth, calmness, extroversion, and low anxiety were closely
related to an attractive smile. Smile exercises were an effective means of
improving the esthetic level of the smile if patients exercised continuously.
CONCLUSION: An attractive smile is important for esthetic treatment. The lip
position, oral condition, personality traits, and smile exercise affect the
esthetics of the smile.
PMID- 10196824
TI - Fabrication of a wax ear by rapid-process modeling using stereolithography.
AB - PURPOSE: The purpose of this article is to describe an automated technique that
creates a mirror-image wax model of the contralateral ear using a rapid
prototyping technique, which allows precise positioning and adaptation to the
deficient side of the face. MATERIALS AND METHODS: Magnetic resonance images
(MRI) are taken of the face and then digitized and reformatted into a 3
dimensional image. The image of the normal ear is extracted, mirrored, and
positioned onto the image of the deformed side of the face. The digitized data,
when used in conjunction with stereolithography, produces a photopolymerized
resin model ear. A model wax ear is created by pouring molten wax into a silicone
mold of the resin model ear. RESULTS: A model wax ear of identical dimensions,
shape, and internal contouring as the contralateral normal ear is created. The
technique allows the undersurface of the model wax ear to be precisely positioned
against the surface contours of the deformed side of the face in 1 patient.
CONCLUSION: The use of stereolithography from MRI scan data is a suitable
technique for producing a model wax ear that fits the deformed side of the face.
The 3-dimensional computer image of the face may also be used to plan the
position (level and protrusion) of the ear.
PMID- 10196825
TI - Effects of cyclic loading on the strength of all-ceramic materials.
AB - PURPOSE: To investigate the effects of fatigue on the strength of materials used
in all-ceramic crowns, the biaxial flexural strength of all-ceramic restorative
materials was measured with precracked and laminated specimens after cyclic
loading. MATERIALS AND METHODS: Two types of all-ceramic systems were used to
prepare specimens: a glass-infiltrated alumina core system (In-Ceram) and a
leucite-reinforced feldspathic porcelain system (IPS-Empress). Monolayer and
laminated disks with a diameter of about 11.75 mm and a thickness of 1.20 +/-
0.05 mm were prepared. The biaxial flexural strength of the specimens that were
polished and/or created with a precrack was measured. Their strength was also
measured following cyclic loading. A cyclic load that was 60% of the mean
breaking load of the specimens (before cyclic loading) was applied to specimens
for 10(5) cycles in 37 degrees C water. RESULTS: Although 20% to 30% of the
polished specimen samples fractured during cyclic loading, the biaxial flexural
strength of specimens that survived the cyclic loading was nearly the same as
that of specimens not subjected to the cyclic loading. The strength of the
alumina system decreased with the introduction of precracks, and nearly all
specimens fractured during cyclic loading. The strength of the leucite system,
however, did not decrease with the presence of precracks, and no fractures were
observed on these specimens during cyclic loading. CONCLUSION: These results
suggest that although the alumina system has high flexural strength, it is more
sensitive to flaws and susceptible to fatigue fracture. The effect of fatigue on
the leucite system appears to be low.
PMID- 10196826
TI - Fracture strength of glass infiltrated-magnesia core porcelain.
AB - PURPOSE: This study determined the fracture strength of magnesia-core porcelain
after using a glass infiltration firing technique. MATERIALS AND METHODS: Eighty
refractory dies were replicated from a stainless steel master die milled to the
dimensions of a maxillary premolar that had been prepared for a porcelain crown.
The core porcelain was applied to the refractory dies using traditional
condensation methods, and then formed into standardized copings using a
centrifugal sculpturing device. The copings were vacuum-fired from 593 degrees C
to 1 of 8 high temperatures. Five copings per temperature were then coated with a
glass-infiltrate and ground back to a standard thickness. The finished copings
were bonded to a duplicate die with an adhesive resin luting system and placed in
an Instron testing machine and loaded to fracture. RESULTS: Analysis of variance
and Student-Newman-Keuls tests demonstrated significant differences among
treatments and temperatures (P < 0.05). A significant increase in fracture
strength was observed after glass infiltration of the magnesia-core porcelain.
Sintering the copings to 871 degrees C or 899 degrees C prior to glass
infiltration gave the highest fracture load values. CONCLUSION: Glass
infiltration significantly increased the fracture strength of the magnesia-core
porcelain.
PMID- 10196827
TI - General dentists' attitudes toward delegation, information, and patient influence
in a prosthodontic context.
AB - PURPOSE: The aim of this study was to investigate attitudes among general
dentists in Sweden in relation to gender, age, prosthodontic activity, and dental
delivery system (private or public). MATERIALS AND METHODS: Questionnaires were
sent to a random sample of 2,059 dentists, and a response rate of 76% (1,567
dentists) was achieved. Among those who responded, 50% were private practitioners
and 50% were publicly employed practitioners; 42% were female and 58% were male.
The questionnaire contained 10 statements aimed at measuring attitudes. Their
dimensionality was analyzed using principal components analysis. The resulting
factors were related to delivery system (public or private), gender, age, job
satisfaction, and weekly working hours used for prosthodontics in multiple
regression models. RESULTS: There was a wide variation in the answers to the
statements, indicating great individual differences in opinions among dentists.
Several distributions differed with respect to gender and delivery system, but
the mean differences between various groups of dentists were small. The most
affirmative attitude was shown for delegation of impression taking to auxiliaries
(mean 6.7; SD 1.8), and the most negative attitude was shown for close
cooperation between dentists (mean 1.8; SD 1.4). The factor analysis gave 3
factors, with a variance explanation of 57%. Regression models for the 3 attitude
dimensions ("patient influence," "delegation," and "patient information") showed
that female dentists felt more positive about delegation and information than
male dentists. The explained variance was very low for all 3 models and varied
from 0.01 to 0.05. CONCLUSION: Although the differences in attitudes between
various groups of dentists were statistically significant, these differences were
small in relation to the large variation in attitudes among individual dentists.
PMID- 10196828
TI - Methods used to select artificial anterior teeth for the edentulous patient: a
historical overview.
AB - PURPOSE: Selecting artificial teeth for a denture is complex when there are no
remaining natural teeth and no pre-extraction records. The aim of this paper is
to review the methods used to select artificial anterior teeth for the
endentulous individual. MATERIALS AND METHODS: The review takes account of the
majority of papers published during the last 100 years and is organized according
to the methods used for determining artificial tooth form. RESULTS: Several
factors have been proposed as aids for artificial tooth selection, and numerous
methods have been devised for the evaluation of reliable esthetic factors in
determining artificial tooth form. CONCLUSION: To date, no universally reliable
method of determining tooth form has been found. The Williams classification
(1914) is the most universally accepted method of determining anterior tooth
form.
PMID- 10196829
TI - Correlation of topography to bond strength of etched ceramic.
AB - PURPOSE: Bonding techniques are commonly used today to ensure the durability of
porcelain laminate veneers and ceramic inlay-onlays, which are esthetically
pleasing solutions to the problem of dental restoration. Acid etching and
silanization of porcelain have been widely used to enhance the retention between
bonding resins and ceramic restorations. The purpose of this study was to
evaluate the effect of surface modifications with 10% hydrofluoric acid gel and a
coupling agent (a dual component silane) on the bond strength of 2 dental
feldspathic ceramics (GC and PVS) bonded with an unfilled resin (Super-Bond).
MATERIALS AND METHODS: Eighty samples of GC and eighty samples of PVS were built
for a mechanical study. Mechanical tests were conducted using a Lloyd T 6000 R
tensile machine, which determined the bond strengths of the 2 ceramics after
different surface treatments (etching or silanization). In the next part of the
study, 10 surfaces of GC and 10 surfaces of PVS were studied with a scanning
mechanical microscope to evaluate the action of hydrofluoric acid gel on the
roughness of the 2 ceramics. RESULTS: Etching ceramic with hydrofluoric acid gel
increased the developed surface of feldspathic ceramics, especially for PVS, but
this treatment was not sufficient to obtain the highest shear bond strength. The
highly positive influence of silanization was shown, particularly for GC ceramic
bonded with an unfilled resin. CONCLUSION: Silane combined with the action of
hydrofluoric acid gel is the most effective surface treatment for ceramic.
PMID- 10196830
TI - Clinical experiences with laser-welded titanium frameworks supported by implants
in the edentulous mandible: a 5-year follow-up study.
AB - PURPOSE: The purpose of this study was to report the 5-year clinical performance
of implant-supported prostheses with laser-welded titanium frameworks and to
compare their performance with that of prostheses provided with conventional cast
frameworks. MATERIALS AND METHODS: On a routine basis, a consecutive group of 824
edentulous patients were provided with fixed prostheses supported by implants in
the edentulous mandible. In addition to conventional gold-alloy castings,
patients were at random provided with 2 kinds of laser-welded titanium
frameworks. In all, 155 patients were included in the 2 titanium framework
groups. A control group of 53 randomly selected patients with conventional gold
alloy castings was used for comparison. Clinical and radiographic 5-year data was
collected for the 3 groups. RESULTS: All followed patients still had fixed
prostheses in the mandible after 5 years. The overall cumulative success rates
were 95.9% and 99.7% for titanium-framework prostheses and implants,
respectively. The corresponding success rates for the control group were 100% and
99.6%, respectively. Bone loss was 0.5 mm on average during the 5-year follow-up
period. The most common complications for titanium frameworks were resin or tooth
fractures, gingival inflammation, and fractures of the metal frames (10%). One of
the cast frameworks fractured and was resoldered. Loose and fractured implant
screw components were few (< 1%). CONCLUSION: Even though the cast frameworks had
a higher success rate, the overall titanium framework treatment result was well
in accordance with the result of the control group. The test groups performed
better after clinicians had gained some experience with the technique, and laser
welded titanium frameworks seem to be a viable alternative to conventional
castings in the edentulous mandible.
PMID- 10196831
TI - Proliferative activity of denture-induced fibrous inflammatory hyperplasia
analyzed by proliferating cell nuclear antigen labeling index.
AB - PURPOSE: Denture-induced fibrous inflammatory hyperplasia (FIH) occurs around the
borders of an ill-fitting denture. There has been no report in the literature
concerning epithelial proliferative activity in FIH. The purpose of this study
was to observe the labeling of proliferating cell nuclear antigen (PCNA) and
evaluate its clinicopathologic results. MATERIALS AND METHODS: The labeling index
(LI) was assessed by using the PCNA, a nuclear protein synthesized mainly in the
G1-S stages of the cell cycle that could be detected immunohistochemically by the
monoclonal antibody PC10. The PCNA LI was assessed in FIH specimens, in
clinically normal specimens 1 cm from the FIH margin (adjacent group), and in
clinically normal specimens located at least 2 cm from the adjacent group; the
last were considered the control group. RESULTS: The mean PCNA LI values in the
basal, parabasal, and overall epithelial layers were similar in FIH and in the
adjacent group and were significantly higher than in the control group.
CONCLUSION: These data support the importance of the surgical treatment of FIH
with wide excision (about 1 cm) since the clinically normal tissue around the
lesion could be histologically altered.
PMID- 10196832
TI - The influence of post length and crown ferrule length on the resistance to cyclic
loading of bovine teeth with prefabricated titanium posts.
AB - PURPOSE: The purpose of this in vitro study was to evaluate the influence of post
and ferrule length on the resistance to cyclic (fatigue) loading of teeth with
prefabricated titanium posts (ParaPost) and crowns. MATERIALS AND METHODS: Ninety
bovine teeth with similar dimensions were mounted in acrylic blocks with
artificial silicone periodontal ligaments. Combinations of post lengths of 5 mm,
7.5 mm, and 10 mm, and ferrule lengths (i.e., the vertical dentinal overlap of
the crown) of 0 mm, 1.25 mm, and 2.5 mm made up 9 different groups consisting of
10 teeth each. The posts were cemented with zinc phosphate cement. Composite
resin cores were made and crowns were cemented. Each test specimen underwent
cyclic loading of 400 N with a frequency of 1 load per second at an angulation of
45 degrees to the long axis of the tooth. RESULTS: All but 2 specimens failed
with a root fracture; in the remaining 2 specimens the core lost retention. A
large variation in the results between the various groups was observed. A
nonparametric 2-way analysis for groups with a natural order revealed that the
fracture resistance to cyclic loading increased statistically significantly with
increasing ferrule length (P < 0.01), whereas increasing post length did not
increase fracture resistance (P = 0.44). CONCLUSION: Ferrule length was more
important than post length in increasing fracture resistance to cyclic loading of
crowned teeth.
PMID- 10196833
TI - Adherence of Candida albicans to the surface of polymethylmethacrylate--E glass
fiber composite used in dentures.
AB - PURPOSE: The use of reinforcing fibers in dentures has raised concerns about
possible increased adherence of yeasts to the surface. The aim of this in vitro
study was to compare the adherence of Candida albicans to the surface of denture
base polymer and to E-glass fibers. MATERIALS AND METHODS: Test specimens were
made from an autopolymerized denture-base resin (Palapress) reinforced with
preimpregnated unidirectional E-glass fibers, which were exposed at the surface.
The test specimens were pretreated with parotid saliva and incubated without
agitation in standardized yeast suspensions (10(8) colony-forming units per mL)
in phosphate-buffered saline at 37 degrees C for 1 hour. The test specimens were
then washed to remove nonadherent cells. After being air dried, they were sputter
coated with gold-palladium for scanning electron microscopy (SEM). To compare the
adherence to different surfaces, the number of yeast cells found either on the
polymer matrix or on the glass fibers was counted from SEM fields (170 microns x
120 microns, 600 x) of randomly selected areas. RESULTS: The mean density of
yeast cell found on the surface of the polymer matrix was significantly higher (P
< 0.001) than that on the surface of glass fibers. The number of adherent yeast
cells found at the interface between the fibers and polymer matrix was high.
CONCLUSION: The adherence of C albicans to E-glass fibers was lower than to
polymer matrix in the denture composite. If fibers are exposed only during
polishing of the composite, the reinforcing material appears not to increase the
adherence of this common oral yeast. However, areas with permanently exposed
fibers may provide mechanical retention for yeast cells at the interface of the
components.
PMID- 10196834
TI - A comparative study of root-end induction using osteogenic protein-1, calcium
hydroxide, and mineral trioxide aggregate in dogs.
AB - Calcium hydroxide has been the material of choice for apexification. The purpose
of this study was to compare the efficacy of osteogenic protein-1 and mineral
trioxide aggregate with that of calcium hydroxide in the formation of hard tissue
in immature roots of dogs. Sixty-four roots of premolars were used. After
induction of periradicular lesions, the canals were debrided and filled with
calcium hydroxide for 1 wk. After the removal of calcium hydroxide, the root
canals received one of the treatment materials in a balanced design. The animals
were euthanized 12 wk later. The degree of hard tissue formation and amount of
inflammation were evaluated histomorphically. Data were statistically evaluated
using ANOVA, chi 2, and Kruskal-Wallis. Mineral trioxide aggregate produced
apical hard tissue formation with significantly greater consistency. The
difference in the amount of hard tissue produced among the three test materials
was not statistically significant. Furthermore, the degree of inflammation was
not significantly different between the various test groups.
PMID- 10196835
TI - In vitro fracture strength of endodontically treated premolars.
AB - The recent introduction of new bonding agents has led some authors to suggest
that certain endodontically treated posterior teeth could be restored with a
bonded restoration instead of a full-coverage crown or onlay. To test the
fracture resistance of endodontically treated premolars restored with and without
bonding agents, we randomly divided 56 intact and caries-free maxillary premolars
into seven groups as follows: unaltered teeth; access only; MOD prep and RCT; MOD
prep, RCT, and amalgam restoration; MOD prep, RCT, and amalgam with 4-META
bonding agent; MOD prep, RCT, and composite resin restoration; and MOD prep, RCT,
and composite resin with 4-META bonding agent. The teeth were subjected to
compressive fracture tests in a Zwick 1435 Universal Testing Machine. Unaltered
teeth and those with access only demonstrated similar fracture strengths. Under
the conditions of this study, there was no significant difference in fracture
strength between the experimental groups.
PMID- 10196836
TI - Comparison of two devices for root canal cleansing by the noninstrumentation
technology.
AB - Optimal cleansing of the root canal system is a prime prerequisite for long-term
success in endodontics. Recently, a new method and device were presented
providing "automatic" root canal cleansing without the need of endodontic
instrumentation. Cleanliness results equivalent to or better than those with
conventional methods were achieved in considerably less time. The purpose of the
present study was 2-fold: (a) optimization of the device to make it applicable to
patients and (b) to measure its effectiveness against the predecessor model. A
total of 156 root canals of 66 freshly extracted vital human molars were cleansed
with the new device and their cleanliness compared with that of 149 canals of 52
molars cleansed previously with the first apparatus. Data indicated that the
smaller new machine produced equivalent or better cleanliness results in the root
canal system using significantly less irrigant (NaOCl).
PMID- 10196837
TI - Corrosion in stainless-steel and nickel-titanium files.
AB - This study evaluated and compared the corrosion susceptibility of stainless-steel
and nickel-titanium (NiTi) endodontic files immersed in sodium hypochlorite. For
each of the stainless-steel files (Kerr K-Flex, Caulk Flex-O, and Union Broach
Flex-R) plus the NiTi files (Union Broach NiTi and Tulsa NiTi), the cutting
flutes of 24 ISO size 20 files were immersed into 5.25% sodium hypochlorite.
Their open circuit potential (OCP) was recorded for 1 h on a strip chart with
high impedance. The strip chart recording for each file was classified into a
stability score: (i) stable, (ii) unstable, or (iii) erratic. The OCP was
measured by a potentiostat and a standard calomel electrode reference. The OCP
classification of unstable and erratic for the files evaluated were as follows: K
Flex (16%), Flex-R (12%), Flex-O (75%), Union Broach NiTi (62%), and Tulsa NiTi
(0%). After OCP testing, each of the 120 files was inspected by light microscopy
at x 25. The frequencies of visually observed corrosion were detected as follows:
K-Flex (2/24), Flex-R (1/24), Flex-O (6/24), Union Broach NiTi (2/24), and Tulsa
NiTi (0/24). There was a significant difference in corrosion frequency between
brands when evaluated by OCP and light microscopy; however, there was no
significant difference between stainless steel and NiTi.
PMID- 10196838
TI - Cytotoxic effects of different concentrations of neutral and alkaline EDTA
solutions used as root canal irrigants.
AB - The cytotoxic effects of neutral and alkaline EDTA solutions were evaluated and
compared with those of sodium hypochlorite solution using an established cell
line: L929. Cytotoxicity was assessed by a quantitative technique at five
observation periods (1, 3, 6, 12, and 24 h). All tested agents showed moderate to
severe cytotoxicity in the present experimental model in a concentration
dependent manner.
PMID- 10196839
TI - An in vitro pulp chamber with three-dimensional cell cultures.
AB - To better simulate the in vivo situation, a three-dimensional fibroblast cell
culture was introduced into an in vitro pulp chamber model. The system was
evaluated by testing a series of dental filling materials. After a 24-h exposure
with (0.3 or 5 ml/h) and without perfusion of the pulp chamber, the tissues were
subjected to a routine MTT assay. Zinc phosphate cement, conventional glass
ionomer cements, a silicone impression material, and zinc oxide-eugenol did not
influence cell viability, compared with untreated controls; but, a light-curing
glass ionomer cement significantly reduced cell survival. Perfusion of the
chambers did not significantly influence the results, but perfusion conditions of
5 ml/h lead to a general decrease of cell vitality. The three-dimensional cell
culture system in an in vitro pulp chamber seems to be a substantial improvement,
because zinc oxide-eugenol does not evoke a cellular reaction (as is the case in
vivo), and the test system is sensitive enough to detect other toxicants.
PMID- 10196840
TI - Stimulatory effect of laser irradiation on calcified nodule formation in human
dental pulp fibroblasts.
AB - The purpose of the present study was to investigate the effect of laser
irradiation on calcified nodule formation in human dental pulp (HDP) cells. HDP
cells were irradiated once with a Ga-Al-As laser for 5 and 10 min, and calcified
nodule formation was determined by von Kossa staining. The laser irradiation
increased the number of calcified nodules in a time-dependent manner. The
activity of alkaline phosphatase and production of collagen and osteocalcin in
conditioned medium were measured. Both were higher in the irradiated group than
in the nonirradiated group. These results suggested that formation of calcified
nodules in HDP cells, as well as in alkaline phosphatase activity, the production
of collagen and osteocalcin were enhanced by laser irradiation.
PMID- 10196841
TI - Growth inhibition of Streptococcus anginosus (milleri) by three calcium hydroxide
sealers and one zinc oxide-eugenol sealer.
AB - The inhibition of growth of Streptococcus anginosus (milleri) by three calcium
hydroxide sealers--calciobiotic root canal sealer (Hygienic Corporation, Akron,
OH), Sealapex (Kerr Division, Sybron Corporation, Romulus, MI), and Apexit
(Vivadent, USA, Amherst, NY)--was compared with a zinc oxide-eugenol sealer: Roth
(Roth International, Chicago, IL). Sixteen brain heart infusion agar plates were
inoculated with S. anginosus. Each plate was divided into five separate areas. In
each area, a 0.1 ml droplet of a given sealer was placed such that each plate had
five areas with the same sealer. There were four plates (for each of the four
sealers) for a total of 20 observation areas to evaluate each sealer. The plates
were incubated at 37 degrees C in a 5% CO2 atmosphere. After varying periods of
incubation, the zones of inhibition of bacterial growth were observed and
measured. Roth sealer had a statistically significant larger mean zone of
inhibition than the calcium hydroxide sealers. However, all of the sealers
exhibited clinically relevant antimicrobial activity. It is likely that the
eugenol in the Roth sealer is responsible for its greater antimicrobial activity.
PMID- 10196843
TI - Occlusal rehabilitation using implants for orthodontic anchorage.
AB - Osseointegration is defined as a direct interaction of bone to an implant
surface. As a result, the implant fixture is immobilized in the bone and lends
itself to function as an anchor for orthodontic tooth movements. When properly
treatment-planned, these implants can also be used as prosthodontic abutments for
single crowns, or removable or fixed partial dentures. This article describes how
implant fixtures were surgically placed within the maxillary and mandibular
arches of a partially edentulous patient, and used for orthodontic anchorage to
reposition the remaining teeth into a more favorable arch position, creating
increased posterior interocclusal space. The fixtures were then restored with
fixed partial dentures to rehabilitate the patient into a mutually protected
occlusion.
PMID- 10196842
TI - Histological study of periapical tissue healing in the rat molar after
retrofilling with various materials.
AB - We histologically examined the effects on the periapical tissue of various dental
filling materials applied as retrofillings in rats and compared them with those
of amalgam. The 4-META-TBB resin Superbond and the light-cured composite resin
produced the least severe inflammatory reaction, with the greatest amount of new
bone. In these specimens, regeneration of a part of the periodontal ligament was
also observed. These results indicate that these materials might be very
biocompatible and thus foster the natural regeneration of the periapical tissue.
PMID- 10196844
TI - Using a colorimeter to develop an intrinsic silicone shade guide for facial
prostheses.
AB - PURPOSE: To determine if using CIE L*a*b* color measurements of white facial skin
could be correlated to those of silicone shade samples that visually matched the
skin. Secondly, to see if a correlation in color measurements could be achieved
between the silicone shade samples and duplicated silicone samples made using a
shade-guide color formula. MATERIALS AND METHODS: A color booth was designed
according to ASTM specifications, and painted using a Munsell Value 8 gray. A
Minolta colorimeter was used to make facial skin measurements on 15 white adults.
The skin color was duplicated using custom-shaded silicone samples. A 7-step
wedge silicone shade guide was then fabricated, representing the commonly
encountered thicknesses when fabricating facial prostheses. The silicone samples
were then measured with the Minolta colorimeter. The readings were compared with
the previous L*a*b* readings from the corresponding patient's skin measurements,
and the relative color difference was then calculated. Silicone samples were
fabricated and analyzed for three of the patients to determine if duplication of
the visually matched silicone specimen was possible using the silicone color
formula, and if the duplicates were visually and colorimetrically equivalent to
each other. The color difference Delta E and chromaticity was calculated, and the
data were analyzed using a coefficient-of-variation formula expressed by percent.
A Pearson Product Moment Correlation Coefficient was performed to determine if a
correlation existed between the skin and the silicone samples at the p < or = .05
level. RESULTS: The highest correlation was found in the b* dimension for
silicone thicknesses of 1 to 4 mm. For silicone thicknesses of 6 to 10 mm, the
highest correlation was found in the L* dimension. All three dimensions had
positive correlations (R2 > 0), but only the 1-mm and 4-mm b* readings were very
strong. Patient and silicone L*a*b* measurement results showed very little change
in the a* axis, while the L* and b* measurements showed more change in their
numbers, with changes in depth for all patient silicone samples. Delta E numbers
indicated the lowest Delta E at the 1-mm depth and the highest Delta E at the 10
mm depth. All duplicated samples matched their original silicone samples to a
degree that visual evaluation could not distinguish any color differences. Using
volumetric measurements, a shade guide was developed for all 15 patients.
CONCLUSIONS: There was good correlation between the patient's colorimeter
measurements and the silicone samples, with the b* color dimension the most
reproducible, followed by the L* and the a*. Silicone samples at 6, 8, and 10 mm
matched the patient the best, and this study showed that silicone samples can be
duplicated successfully if a good patient-silicone match is obtained. Rayon
flocking fibers and liquid makeup are effective at matching facial prostheses and
can be used to develop a simple shade guide for patient application.
PMID- 10196845
TI - Working times and dimensional accuracy of the one-step putty/wash impression
technique.
AB - PURPOSE: Using the one-step polyvinyl siloxane impression technique, this study
compared the effect of putty material working time on the dimensional accuracy of
recovered improved stone casts. MATERIALS AND METHODS: An acrylic resin master
cast was fabricated with embedded reference points to enable both horizontal and
vertical measurements. Four commercially available polyvinyl siloxane impression
putties with light body washes were evaluated: 1) Extrude (Kerr), 2) Cutter
(Coltere), 3) Express (3M), and 4) Reprosil (Caulk). Each putty was mixed by hand
for 30 seconds, placed in a plastic stock tray, and seated on the master cast at
0, 30, 60, 90, and 120 seconds after mixing (N = 100, n = 5). The impressions
were poured in improved stone, and vertical and horizontal measurements were made
to 0.001 mm between reference points on recovered casts using an optical
traveling microscope. ANOVA (p < or = .05) was used to compare vertical and
horizontal measurements to master cast dimensions. RESULTS: No statistically
significant difference was found among casts for all materials and time periods
tested. When horizontal measurement ranges were evaluated, Extrude casts
exhibited the widest range of measurement, especially when the trays were seated
at 90 and 120 seconds. When vertical measurement ranges were evaluated, Express
casts at 120 seconds exhibited the widest range. CONCLUSIONS: A high range of
variability in vertical and horizontal dimensions occurred at the later time
periods, especially for Extrude and Express casts. As a result of rapid
polymerization and poor flow properties of putty materials, the impression tray
should be seated within 60 seconds after putty mixing to reduce dimensional
variability of recovered casts.
PMID- 10196847
TI - Computed tomographic scan template for maximum accuracy of reformatted CT scan
images.
AB - The dental computed tomographic (CT) scan is useful in presurgical planning for
implant prosthodontics. To provide accurate information, the patient must be
positioned properly during the scan procedure. This article describes a method
for fabricating a template that provides guidance to the CT technologist for
desired head orientation of the patient.
PMID- 10196848
TI - Template for surgical crown lengthening: fabrication technique.
AB - This article describes a technique for the easy fabrication of a template to
facilitate surgical lengthening of the clinical crown to enhance esthetics and/or
increase retention of a fixed prosthesis. The use of this surgical guide should
result in more predictable clinical results.
PMID- 10196846
TI - Effect of polymerization mode on bond strengths of resin adhesive/cement systems.
AB - PURPOSE: The purpose of this study was to examine the effect of resin
adhesive/cement system primer and cement polymerization mode (auto- vs dual
polymerized) on the shear bond strength to dentin. MATERIALS AND METHODS: Dentin
surfaces of 90 bovine teeth were polished to 600 grit. The dentin was etched for
15 seconds with phosphoric acid, rinsed, and blotted. Three adhesive systems, All
Bond 2, Prime & Bond 2.1 Dual-Cure, or Scotchbond Multi-Purpose Plus, were
applied. Three primer polymerization methods were used with each system: dual
polymerized, autopolymerized, or strictly following manufacturers'
recommendations. Resin cements, which were also either auto- or dual-polymerized,
were applied to dentin using gelatin capsules. Shear bond strengths were
determined using an Instron universal testing machine. RESULTS: The greatest bond
strength, 15.4 MPa, was found with the Scotchbond system when the primer was dual
polymerized and the cement was autopolymerized. The lowest bond strength, 7.5
MPa, was found with All-Bond 2/Duo-Link, when the primer and cement were dual
polymerized. The autopolymerization mode produced the highest mean bond strength
for All-Bond 2, while dual-polymerization of primer and cement resulted in the
highest mean bond strength for Prime & Bond 2.1. Scotchbond Multi-Purpose Plus
was least affected by the polymerization method. Two-way ANOVA showed that the
interaction between the type of adhesive system and the method of polymerization
significantly influenced bond strength (p = .0001). CONCLUSIONS: The effect of
the primer polymerization method on ultimate bond strength was different for each
adhesive system evaluated. More research is needed to elucidate the interaction
between adhesive system and method of polymerization on bonding of resin cements
to dentin.
PMID- 10196850
TI - A technique to stabilize record bases for Gothic arch tracings in patients with
implant-retained complete dentures.
AB - Clinicians have long expressed concern about the accuracy of the Gothic arch
tracing for recording centric relation in edentulous patients. With the use of
dental implants to assist in retaining complete dentures, the problem of
inaccurate recordings, made for patients without natural teeth, can be
significantly reduced. This article presents a technique that uses healing
abutments to stabilize the record bases so that an accurate Gothic arch tracing
can be made.
PMID- 10196849
TI - The Twin-Flex removable partial denture: design, fabrication, and clinical usage.
AB - A rationale for the use of Twin-Flex clasps is presented. Twin-Flex clasps may
provide improved esthetics, an increased number of clasping sites, and enhanced
patient comfort when compared with conventional clasping systems. Two fabrication
methods are described, and departures from conventional clasping techniques are
explained.
PMID- 10196851
TI - Evidence-based dentistry: is it worth changing our approach to practice?
PMID- 10196852
TI - Preimpregnated, fiber-reinforced prostheses. Part II. Direct applications:
splints and fixed partial dentures.
AB - This article is the second in a series that describes the development, physical
properties, and clinical applications of fiber-reinforced composite materials.
The development of fiber-reinforced composite technology has opened new avenues
for fabricating direct tooth replacements and splints that are esthetic and
simple in design and execution and have the potential for excellent durability.
Splinting techniques for hypermobile dentitions or postorthodontic retention and
the replacement of anterior and posterior teeth using a groove preparation, a
denture tooth, and a fiber-reinforced composite framework will be described.
PMID- 10196853
TI - An evaluation of a chemical cautery agent and an anti-inflammatory ointment for
the treatment of recurrent aphthous stomatitis: a pilot study.
AB - OBJECTIVE: Recurrent aphthous stomatitis is a very common condition, currently
treated with anti-inflammatory agents, which palliate the symptoms. The purpose
of this clinical trial was to compare a medication commonly used to treat
recurrent aphthous stomatitis, Kenalog-in-Orabase, and a newer agent, Debacterol.
METHOD AND MATERIALS: Sixty patients diagnosed with recurrent aphthous stomatitis
were enrolled in the study. Twenty patients were assigned to each of the two
treatment groups, and 20 age- and sex-matched patients were assigned to the
control group, which received no treatment. After the diagnosis was made,
clinical examinations and ulcer measurements were performed, and a subjective
evaluation of symptoms (100-mm visual analog scale) was completed by each
subject. The subjects did not use any other medications. Both agents were applied
topically (the frequency varied depending on the group of subjects) at specified
intervals. Ulcer measurements and subjective evaluations were made at days 0, 3,
6, and 10 for all subjects. RESULTS: In both treatment groups, by day 10, 100% of
the ulcers had clinically healed and were no longer causing pain. Patients in the
Debacterol group reported a significantly greater decrease in pain at 3 days (>
70%) than did subjects in the other groups (< 20%), although the size of the
ulcer did not differ significantly in any of the groups. After day 6, 80% of the
ulcers in the Debacterol group had clinically disappeared and no longer caused
symptoms, as compared to about 30% in the other groups. CONCLUSION: Patients
subjectively reported significantly greater relief from symptoms with Debacterol
than with Kenalog-in-Orabase or no treatment. The relief of symptoms associated
with recurrent aphthous stomatitis may or may not correspond to clinical
improvement, and these two topical medications may affect signs and symptoms of
the lesions differently.
PMID- 10196854
TI - Evaluation of the handling of a new compomer and novel dispensing system in
general dental practice.
AB - OBJECTIVE: Easy handling of materials is essential to the production of good
clinical results. The handling properties of a new compomer material and its
novel primer/adhesive-dispensing system were tested in clinical use. METHOD AND
MATERIALS: Ten general dental practitioners used the new material and dispenser
for 3 weeks and completed a questionnaire regarding the handling, esthetics, and
ease of use. They were asked to compare the new material to the compomer, resin
composite, and glass-ionomer materials normally used in their own practice.
RESULTS: The material scored a mean of 4.4 for dispensing convenience on a linear
scale of 1 (inconvenient) to 5 (convenient) and 4.6 for ease of use (5 = easy to
use, and 1 = difficult to use). The dispensing system achieved a high rating of
4.9 for convenience (5 = convenient, and 1 = inconvenient). CONCLUSION: The new
material received ratings that were superior to those of the glass-ionomer and
compomer materials normally used by the evaluators and similar to ratings of the
resin composite normally used.
PMID- 10196855
TI - Single-use, disposable, presterilized light-activation probe: the future?
AB - OBJECTIVE: The purpose of this study was to compare a single-use, disposable,
presterilized light activation probe with an equivalent autoclavable probe. Light
output, heat generation, and depth of cure were investigated. METHOD AND
MATERIALS: Ten disposable and two reusable probe tips were tested. Three maximum
light output readings for each tip were recorded with a radiometer. Heat
generation at the probe tip was recorded, at 30-second intervals over a five
minute period, with a thermocouple probe placed under a 3-mm-thick glass slide.
After light-activated "compomer" was placed in a sectional two-piece stainless
steel mold and cured, depth of cure was evaluated using the scrape technique.
RESULTS: With respect to light output and depth of cure, there were no
statistically significant differences between probe types, but the disposable
probe generated significantly less heat. CONCLUSION: The disposable probe
performed clinically as well as an autoclavable counterpart with respect to light
output, heat generation, and depth of cure.
PMID- 10196856
TI - In vitro shear bond strength of two resin composites to dentin with five
different dentin adhesives.
AB - OBJECTIVE: The aim of this in vitro study was to evaluate the shear bond strength
to dentin of five different dentin bonding agents in combination with two resin
composites (Tetric and Z-100). METHOD AND MATERIALS: Human third molars were
selected for the study, and cylindrical posts of either Tetric or Z-100 were
bonded vertically to a standard flat dentinal area, prepared on the buccal
surface of the teeth. A chisel-shaped shearing blade, attached to the crosshead
of a universal testing machine, was positioned so that its edge was immediately
adjacent to the adhesive joint. The shear bond strengths to dentin of 10 resin
composite-dentin adhesive combinations were measured. RESULTS: The results showed
that the bond strength of dentin bonding agents may depend on the choice of
restorative material. The in vitro bond strength of dentin bonding agents also
differed significantly. In several cases, the bond strength exceeded the cohesive
strength of dentin. CONCLUSION: It seems important for clinicians to be
acquainted with the variation in bond strength values that is experienced with
any bonding system.
PMID- 10196857
TI - Role of chemical erosion in generalized attrition.
PMID- 10196858
TI - Evidence-based dentistry: what is it, and what does it have to do with practice?
Anecdote vs. data--a case for evidence-based decision making.
PMID- 10196860
TI - Evidence-based dentistry: what is it, and what does it have to do with practice?
The relevance of evidence.
PMID- 10196859
TI - Evidence-based dentistry: what is it, and what does it have to do with practice?
It works in my hands. Why isn't that good enough?
PMID- 10196861
TI - Evidence-based dentistry: what is it, and what does it have to do with practice?
Assessing risk improves predictability of treatment outcomes.
PMID- 10196862
TI - Evidence-based dentistry: what is it, and what does it have to do with practice?
The methods of evidence-based dentistry.
PMID- 10196863
TI - Teaching minority students.
PMID- 10196865
TI - Using support programs to facilitate academic success in African American
students.
AB - Academic problems resulting from both internal and external factors affect the
ability of students to be successful in their course study. Verbalization about
problems and concerns to supportive teachers and counselors is not uncommon.
However students often do not possess the knowledge and skills needed to handle
these problems. This article describes support programs that have been put into
place at Indiana University School of Nursing to assist students with specific
problems and describes the benefits associated with these programs.
PMID- 10196864
TI - The role of the historically black college and university (HBCU) in student
learning.
AB - This article takes a brief view of the role of Historically Black Colleges and
Universities (HBCUs) in the teaching/learning of African American students. The
article also presents Mrs. Ray Kornegay's view on her personal experience at a
Historically Black College/University. Mrs. Kornegay's views are congruent with
the espoused beliefs found in the article.
PMID- 10196866
TI - Teaching nursing research to minority students.
AB - Teaching nursing research can be a challenging role for nurse educators. Even
when the nurse educator is equipped with a large arsenal of teaching strategies
designed to promote student interest, that students will leave the class with a
basic understanding of the research concepts is not guaranteed. It is important
to know the audience, which in this case are the students, so that the nurse
educator can select teaching strategies that will assist the students in
achieving course objectives. The purpose of this article is to describe the use
of two teaching strategies that have been effective in teaching nursing research
to minority students.
PMID- 10196867
TI - The Mentoring Program at Fayetteville State University: a key to success for
minority students.
AB - This article gives a detailed description of the Mentoring Program at
Fayetteville State University. The program was developed and in implemented by
the University College of Fayetteville State University and has played a key role
in the academic success of students. This purpose of this paper was to provide
information about an approach that may assist nursing faculty teaching minority
students and others to more effectively promote their academic success.
PMID- 10196868
TI - Philosophy at the grass roots.
PMID- 10196869
TI - Nurse prescribing: the wider view.
PMID- 10196870
TI - The process of decision-making by emergency nurses.
AB - The manner in which emergency nurses make decisions is a fundamental component of
their practice but has not been widely researched. A review of nursing literature
revealed that the decision model used by nurses in other clinical areas was a
hypothetico-deductive method of clinical reasoning. It appeared cogent to
determine whether the hypothetico-deductive decision-making theory held true for
emergency nursing. Accordingly, the overall objective in this study was to
establish the method of decision-making used by emergency nurses. A modified
grounded theory framework was chosen to validate the model put forward by White
et al. Three participants, all clinical nurse specialists, were given five
clinical situations to respond to and asked to describe and discuss their
thoughts when arriving at a diagnostic conclusion. The results demonstrated that
the use of the hypothetico-deductive model of clinical reasoning, utilising
verbal, non-verbal and other sources of information, was used by clinical nurse
specialists in the emergency setting.
PMID- 10196871
TI - Nurses' knowledge and attitudes concerning pain management in an Australian
hospital.
AB - Pain management is widely acknowledged as being a significant concern for many
health professionals. Effective management of patients' pain is a crucial nursing
activity dependent on accurate pain knowledge, attitudes, and assessment. The
development of a questionnaire by McCaffery and Ferrell allowed the
quantification of registered nurses' knowledge and attitudes concerning their
pain management decisions. When this questionnaire was applied to registered
nurses working in four different hospital departments within an Australian
hospital, the results showed that many nurses have inadequate knowledge and
attitudinal barriers that may hamper effective pain management decisions. These
results demonstrate that Australian registered nurses may have knowledge
deficiencies and attitudinal barriers similar to their overseas counterparts.
PMID- 10196872
TI - Reliability and validity of an instrument to measure tissue hardness in breasts.
AB - The author investigated the effectiveness of the Roberts Durometer, an instrument
developed to measure human tissue hardness for a study on breast engorgement. The
instrument is a small portable pressure gauge comprising a probe attached to a
spring and contained in a tubular housing, connected to a dial gauge. The
instrument was first trialed using foam rubber of differing hardness and football
bladders of differing hardness. It was then used to measure the hardness of a non
pregnant, non-lactating human breast, followed by trials on postpartum women
comparing breast tissue hardness on the day of birth with that of subsequent
days. The instrument detected significant differences in hardness of foams,
football bladders and human breast tissue. It was therefore considered suitable
for measuring, in both research and clinical applications, hardness of breast
tissue, which is a major physical feature of breast engorgement. Other clinical
applications could include the hardness of abdominal and other skin tissues in
conditions such as ascites, peritonitis and cellulitis.
PMID- 10196873
TI - Beyond interactivity....
PMID- 10196874
TI - Nurses' perceptions of their professional growth on completion of two years of
postgraduate education.
AB - In a climate of diminishing financial resources in service industries such as
health care and education, it is not surprising that a focus on measuring and
ensuring appropriate outcomes is widespread. Graduate education has the potential
to make a significant difference to the professional behaviour of graduates.
Postgraduate nursing coursework programs have been developed and offered in such
a climate, many now charging full course fees, which no doubt stimulates
participants and employers to look for value for money in terms of outcomes. A
ten year longitudinal study began in 1992 and was designed to determine the
impact of postgraduate coursework nursing education on the careers and the
professional and personal development of graduates. This paper reports graduates'
perception of their personal and professional growth in terms of professional
activities such as writing for publication, research, mentoring, and involvement
in professional organisations at the completion of their university course.
Respondents indicated the course had contributed to increased professional
behaviours in all aspects and to a marked improvement in their clinical
confidence. Improved self esteem and increased participation in professional
activities reflects changing attitudes towards nursing work that have important
implications for improved quality of patient care.
PMID- 10196875
TI - Therapeutically conducive relationships between nurses and patients: an important
component of quality nursing care.
AB - The relationship between nurses and patients was identified as an important
component of quality nursing care in two grounded theory studies carried out
concurrently in Perth, Western Australia. Interviews with 22 nurses and 23
patients provided the primary sources of data. Analysis was performed using the
constant comparative method. Comparison of the findings of these two studies
focussed on aspects of the nurse-patient relationship and revealed additional
information concerning the establishment of relationships, the association with
quality nursing care, as well as factors influencing relationship development.
This research demonstrated that the overriding contextual condition needed for
relationship development was the availability of adequate time.
PMID- 10196876
TI - The transition experience of epilepsy patients/families: results of a telephone
survey.
AB - Little has been written about the transition experiences of persons with epilepsy
and their families. The results of the survey presented in this report support
the notion that transition from pediatric to adult care for persons with chronic
illness can be very painful. The sadness produced by the ending of close
relationships, and fear and uncertainty about the future are commonly experienced
emotions at this time. Careful assessment and planning by the entire team coupled
with cooperative efforts between adult and pediatric care providers are necessary
to ensure a smooth and seamless transition from pediatric to adult epilepsy care.
PMID- 10196877
TI - Truly a team effort.
AB - Jane was a healthy 16 year old girl who attended a high school dance and
subsequently had a grand mal seizure--her first! She was taken home, developed a
decreasing level of consciousness and was admitted to the local hospital, where
it progressed to status epilepticus. We will describe the classifications of
seizures including status epilepticus, which demands the highest level of
clinical expertise and attention to preventative medicine, for a desirable
outcome. During the eleven months of care a massive multi disciplinary team
approach was instituted which extended across borders. Jane's story demonstrates
a truly Neuroscience team effort from acute care to a rehabilitation center to
home.
PMID- 10196878
TI - [Intervention of a support group based on a systemic approach with couples in
which one partner has a brain tumor].
PMID- 10196879
TI - The Program Recognition Committee: an introduction.
PMID- 10196880
TI - Getting the written word out.
PMID- 10196881
TI - The Internet and resources across the lifespan: focus on children.
PMID- 10196882
TI - Opportunities for holistic practice in managed care.
PMID- 10196883
TI - Increasing staff knowledge regarding resident transfers.
PMID- 10196884
TI - Geriatric pain "think tank".
PMID- 10196885
TI - Complementary and alternative techniques and systems in long-term care
facilities.
PMID- 10196886
TI - So now you are the director of nursing...
PMID- 10196887
TI - Congress hears about malnutrition in nursing homes and the influence of staffing.
PMID- 10196888
TI - SUPPORT revisited: the nurse clinician's perspective. Study to Understand
Prognoses and Preferences for Outcomes and Risks of Treatment.
AB - SUPPORT (the Study To Understand Prognoses and Preferences for Outcomes and Risks
of Treatment) has brought to the fore the complexities-involved in end-of-life
decision making. The article addresses the use of aggressive treatment in
patients with poor prognoses, patient preferences, and the effects of advance
directives on the care of the seriously ill patient. Discussion of end-of-life
decisions is recommended among the patient, family members, and physician before
the hospitalization, as is improved exposure to alternatives to aggressive
treatment, such as hospice and terminal care units.
PMID- 10196889
TI - Hospice: what gets in the way of appropriate and timely access.
AB - Although hospice is viewed as highly effective in managing a good death, this
service remains on the fringe of traditional medical care and is underutilized in
the United States today. The same reimbursement criteria that facilitate access
to hospice care for many also create barriers for others or exclude them
altogether. The article examines who is and who is not receiving hospice care and
why. Interventions and corrective actions are proposed.
PMID- 10196890
TI - Planning for death and dying while healthy: lessons from the Gulf War
mobilization.
AB - To enable nurses to assume an active role in helping patients and families
discuss and plan ahead for end-of-life decision making, factors that influence
response to being asked to consider one's death while one is still healthy need
to be considered. Members of the National Guard were interviewed about the
cognitive, behavioral, and affective responses they had when they were asked to
make plans and decisions to be implemented in the event of their injury or death
as part of mobilization for the Gulf War. Content and thematic analyses revealed
six patterns in their responses: reference to a context of meaningfulness;
recognition of infrastructure that provided direction; awareness of social
support; overriding concern for family; denial and avoidance, most notably in the
service of protecting family members; and focus on tasks. Nurse practitioners and
educators can use these findings to guide program format and content as well as
future research.
PMID- 10196891
TI - Facing death: donor and recipient responses to the gift of life.
AB - Bone marrow transplantation is an increasingly preferred method of treatment for
patients with aplastic anemia, some forms of leukemia, and certain tumors, such
as lymphoma and breast cancer. When the patient's only alternative is death,
psychosocial and cultural aspects of the relationship between the donor and the
recipient become of paramount importance. In relation to organ transplantation,
the gift has a special emotional meaning because it signifies life and creates a
spiritual bond between the donor and the recipient. The article explores the
theme of gift exchange and its psychosocial implications in bone marrow
transplant donors and recipients. The impact of the relationship of the donor to
the recipient is of particular interest because a live donor is indicated for all
bone marrow transplants. The influence of cultural and religious attitudes also
is investigated.
PMID- 10196892
TI - Reflections on loss without death: the lived experience of acute care nurses
caring for neurologically devastated patients.
AB - The article reports the lived experiences of eight acute care nurses who cared
for three patients with severe brain injury. The patients were hospitalized for
months, primarily as a result of family dynamics. Semistructured interviews of
the nurses were audiotaped, transcribed, and analyzed for common themes that
described their experiences. Research focused on what the nurses experienced
regarding patient care and how they interpreted their experiences. Seven themes
were uncovered: fear and vulnerability, trying to connect (with patients),
empathy, futility, feeling abused (by families), struggling for support (from
colleagues and physicians), and seeking affirmation through physical care.
General interpretations of the experience were negative.
PMID- 10196893
TI - Nurse anesthetist reaction to the unexpected or untimely death of patients in the
operating room.
AB - Certified registered nurse anesthetists (CRNAs) experience the unexpected death
of the their patients much differently than other nurses. Unlike all other
nurses, they are held directly responsible for maintaining their patients'
physiologic parameters in the face of surgical and pharmacologic insults and not
only for selecting the types of anesthetic and adjuvant drugs but also for
manipulating their doses on a minute-to-minute basis. Four factors significantly
enhance their stress: the presence of an unrescinded advance medical directive
and/or do not resuscitate order; the harvesting of vital organs; psychologic
factors, including distractions, errors in clinical judgment, fatigue, boredom,
or lack of vigilance; and legal threats. Unless CRNAs have significant coping
skills firmly in place, any of these stresses may cause them to deteriorate
physically, emotionally, or professionally.
PMID- 10196894
TI - Chronic sorrow: parents' lived experience.
AB - The article compares the literature on chronic sorrow with the life experiences,
memories, and opinions of two health care professionals who are the parents of a
profoundly mentally retarded adult child. Both the literature and these parents'
experiences confirm the lasting nature of chronic sorrow. A lifetime of ongoing
losses experienced by these parents is compared with loss resulting from the
death of a loved one. This sadness without end continues to be a force in the
lives of these parents even though they no longer serve as caretakers for their
child. The article recommends interventions that health care workers can use with
parents of retarded children.
PMID- 10196895
TI - Transformation through grieving: art and the bereaved.
AB - The literature on grief has focused primarily on the grieving process and
individual manifestations of grief. Little has been written, however, about the
transformative or growth potential of grief. The article focuses on the use of
art therapy in an adult bereavement group and the potential benefits of using
expressive art therapy in bereavement work. The art therapy activities provided
the group members with occasions to express a full range of feelings and
opportunities for them to reflect on their individual views of themselves.
PMID- 10196896
TI - The story of Rabbia, a dying person.
AB - Many nurses report that caring for the dying and the dead is the most difficult
situation they face. Several factors contribute to this anxiety: inexperience,
sociocultural influences, and the lack of education about death. Current nursing
practice in caring for the dying is philosophically steeped in the Western
medical model. From this viewpoint, death is considered an enemy, and its
occurrence implies that the practitioner has failed. The article explores how
nursing care of the dying and dead is influenced by multicultural dimensions:
Western medicine, societal norms, and religious beliefs. The nursing care of a
dying American Muslim woman is compared with the care provided by the patient's
family and religious community.
PMID- 10196897
TI - Collaborative practice: a nursing perspective of the psychiatric
interdisciplinary treatment team.
AB - The article describes the evolution of collaborative practice across the
continuum of care of nurse members of two psychiatric interdisciplinary treatment
teams in an inpatient mental health care unit and a psychiatric partial hospital
program. The benefits and difficulties of the process are examined in the context
of Bowen's family systems theory and a patient case study. There is evidence that
patients on these two units have benefited from the improved communication and
coordinated care arising from collaborative practice. The sharing of expertise,
insights, and knowledge has led to individual professional and personal growth
for members of the treatment teams.
PMID- 10196898
TI - Interdisciplinary education in clinical ethics: a work in progress.
AB - Clinical decision making and, broadly speaking, patient care are increasingly
collaborative endeavors dependent on the integration of the profession-specific
knowledge, skills, and perspectives of physicians and nurses. Conflicts over the
ethical dimensions of clinical decision making often arise from these differing
but complementary perspectives. Neither medical nor nursing education adequately
prepares future clinicians for these realities of practice. At Georgetown
University, students and faculty in medicine and nursing have developed an
interdisciplinary curriculum in clinical ethics. The curriculum will bring
together medical students and graduate nursing students with the aim of educating
and training them to analyze and resolve dilemmas in clinical ethics critically
and collaboratively.
PMID- 10196899
TI - Holism in the care of the allogeneic bone marrow transplant population: role of
the nurse practitioner.
AB - In the last 40 years, allogeneic bone marrow transplantation (BMT) has progressed
from the laboratory and animal models to benefit humans with life-threatening
illnesses. Therapeutic outcomes have continued to improve, as has long-term
survival. The advent of this advanced technology in medicine has produced
survivors of serious illness, patients who otherwise would have died years
earlier. The challenge for nursing in this rapidly growing field is to provide
comprehensive, quality care to a sick population. The article attempts to develop
Watson's concept of human care through the role of the nurse practitioner.
Allogeneic BMT is explained, and Watson's theory and its application to BMT are
explored.
PMID- 10196900
TI - Nurse, physician, and consumer role responsibility perceived by health care
providers.
AB - The article describes a study that addressed perceptions of unilateral and
egalitarian role functions for nurses, physicians, and consumers in a long-term,
345-bed psychiatric facility in the western United States. Findings indicated
that physicians desired to retain authority for health care decisions and that
nurses, social workers, and hospital administrators preferred collaborative
practice. Support for shared responsibility increased among psychiatric
technicians with years of experience. Experience did not alter the attitudes of
physicians, occupational therapists, and recreational therapists for physician
dominance. With experience, nurses increased their belief in nurse
responsibility. Despite evidence for collaborative decision making, results of
this study indicate that attitudes of health care providers may prevent this
tenet from being actualized.
PMID- 10196901
TI - The impact of physician-nurse interaction on patient care.
AB - The perceptions of physicians and nurses vary in a number of respects, including
the extent to which collaboration and joint decision making are valued, the
definition of what constitutes adequate and appropriate interprofessional
communication, the quality of nurse-physician interactions, and the understanding
of respective areas of responsibility as well as patient goals. Reasons for these
differences have been attributed to gender, historical origins of the two
professions, and disparities between physicians and nurses with regard to
socioeconomic status, education, and socialization. Failure of physicians and
nurses to interact in a coordinated and positive fashion results in unhealthy
work environments and poor patient outcomes. Both professions must examine their
will to improve interprofessional interactions.
PMID- 10196902
TI - Developing a shared language: interdisciplinary communication among diverse
health care professionals.
AB - Multidisciplinary teams of nurses, physicians, and other professionals may have
difficulty communicating because of inconsistent theoretical underpinnings. A
theoretical base that spans both clinical outcomes and professional boundaries is
needed. The web of causation is a theoretical framework that provides a platform
of communication connecting issues related to infant mortality among various
health-related professions. It includes professional, community, and
institutional issues relevant to pregnant women and new mothers as infant
caregivers. The article discusses how the web was used for interdisciplinary
health care professional interaction and how it was used to develop a series of
research protocols that will affect the care of mothers and infants in the
District of Columbia.
PMID- 10196903
TI - A holistic interdisciplinary health care research model.
AB - Collaboration, when viewed as a nonhierarchic endeavor based on a sharing of
power and authority, may not be an ideal model for interdisciplinary research. A
cooperative venture in which participants willingly join in planning, making
decisions about, and implementing a project supervised by a principal
investigator is historically the successful structure for interdisciplinary
research. A holistic model of mutually respectful cooperation in a hierarchic
team is a more realistic goal for interdisciplinary research efforts.
PMID- 10196905
TI - Nursing and medical student teaming for service learning in partnership with the
community: an emerging holistic model for interdisciplinary education and
practice.
AB - To meet the health needs of communities today, health professionals need to be
trained in working with persons from various cultural backgrounds, practicing
disease prevention and health promotion in community-based settings, and working
in teams with other professionals. The article focuses on interdisciplinary
teaming for education and practice. In this model, medical and nursing students
partner with communities to plan and deliver health promotion education programs
and activities. Four service learning projects providing collaborative teaming
opportunities as part of the Health Professions Schools in Service to the Nation
Program are described. Interdisciplinary service learning has benefits for the
community, students, and faculty and will prepare nurses and physicians to have a
positive impact on care through future interdisciplinary collaboration in
community-based settings.
PMID- 10196904
TI - Partners in care: a model of collaboration.
AB - It is estimated that 3 million persons in the United States have congestive heart
failure. This diagnosis accounts for more than 5% of total health expenditures. A
method to decrease the costs of health care was initiated through the partners-in
care model of collaborative practice. A research study exploring the use of nurse
case managers in collaboration with cardiologists and primary care physicians is
being conducted with persons older than 65 years. This care encompasses both
inpatient and outpatient care. The intervention comprises nurse visits in the
hospital and in the home as well as telephone support for 6 months after the
index hospitalization. The outcomes of quality of life, functional status,
mortality, morbidity, and costs are being examined. Collaborative health care
partnerships may be an effective strategy to decrease health care costs and
improve quality of life and functional status of older persons with congestive
heart failure.
PMID- 10196906
TI - Mental health care: a collaborative, holistic approach.
AB - Managed care has dramatically transformed mental health care. The solo physician
practice, once the dominant mode of delivery of care, has almost disappeared.
Multidisciplinary, collaborative practices have emerged as flexible, cost
effective alternatives. The article describes a holistic, collaborative model of
mental health care. A holistic model includes the professionals, administrative
staff, patients, and families in the treatment plan and maximizes collaboration.
Cooperation and trust among all the individuals involved are essential to ensure
a comprehensive plan to restore health.
PMID- 10196907
TI - Consulting on critical care--mental as well as physical.
PMID- 10196908
TI - Intensive therapy unit nurses' beliefs about and attitudes towards visiting in
three district general hospitals.
AB - The beliefs and attitudes of intensive therapy unit (ITU) nurses regarding
visiting of critically ill patients are believed to be influenced by many
factors, such as the need to promote patient rest, the need to prevent
physiological and psychological complications to the patient and the need to
improve communications between all parties. In this paper, some of the factors
are examined with attempts to establish whether there are any correlations
between such factors as the length of time individual nurses have worked in the
area, their professional qualifications, their job satisfaction and their
perceptions of visiting and visitors. Sixty-eight nurses from three general ITUs
situated in district general hospitals were interviewed. The conclusion was that
nurses still have many negative beliefs and attitudes towards visiting and
visitors. ITU nurses in this study generally appeared to consider the effects of
visiting pessimistically, suggesting they believe they are doing so in the best
interests of the patients, themselves and the ITU itself.
PMID- 10196909
TI - Inhaled nitric oxide: are the safety issues being addressed?
AB - Interest in the therapeutic uses of Nitric Oxide (NO) has gathered pace over the
last decade. It is no exaggeration for the UK Guidelines on the Use of Inhaled
Nitric Oxide (Cuthbertson et al. 1997) to say that 'the use of inhaled nitric
oxide in the UK has become commonplace'. The index of the third edition (1990) of
TE Oh's notable Intensive Care Manual carries no reference to it. Yet, from its
origins in obscure research, the discovery of NO has promised the development of
therapies which might include the revolutionary transformation of approaches to
the treatment of septic shock. It also holds promise in the treatment of acute
respiratory distress syndrome (ARDS). It is in this context that this discussion
will seek to raise fundamental questions about the health and safety aspects of
this substance.
PMID- 10196910
TI - Effects of extended preoperative information on perioperative stress: an
anaesthetic nurse intervention for patients with breast cancer and total hip
replacement.
AB - An anaesthetic nurse intervention was performed in order to evaluate the effects
of extended preoperative information, given by anaesthetic nurses, on
perioperative stress in patients operated on for breast cancer or total hip
replacement (THR). Forty-six consecutive patients scheduled for surgery for
breast cancer, and 55 for THR, were randomized into two groups which were given
different modes of preoperative information. Patients in the control group were
informed about pre- and postoperative routines by a ward nurse. Patients in the
intervention group were given extended formalized information by an anaesthetic
nurse. Wilcoxon rank sum test was used to show relations between variables. There
were no significant differences between the intervention group and control group
for patients with breast cancer or for patients with THR. Breast cancer patients
in the intervention group were significantly more anxious than THR patients in
the intervention group (P < 0.01). Breast cancer patients in the intervention
group showed the highest anxiety scores on the Hospital Anxiety and Depression
Scale (HADS) scale on the day of surgery. This information may reflect an
increased level of anxiety due to the extended information given preoperatively.
The information may thus have had a negative effect on breast cancer patients,
resulting in an increased state of anxiety. The result indicates a need for
individualized modes of information to provide a proper balance between enough
and too much information.
PMID- 10196911
TI - Cardiac and circulatory assessment in intensive care units.
AB - As healthcare delivery changes in critical care, nursing continues to evolve and
develop. Nursing skills are expanding to incorporate skills once seen as the
remit of the medical profession. Nurses are now equipping themselves with the
skills and knowledge that can enhance the care they provide to their patients.
Assessment of patients is a major role in nursing and, by expanding assessment
skills, nurses can ensure that patients receive the care most appropriate to
their needs. Nurses in critical care settings are well placed to carry out a more
detailed assessment, which can help to focus nursing care. This article describes
the step-by-step process of undertaking a full and comprehensive cardiac and
circulatory assessment in a clinical setting. It identifies many of the problems
that patients may have and the signs that the nurse may note whilst undertaking
the assessment.
PMID- 10196912
TI - Should relatives of patients with cardiac arrest be invited to be present during
cardiopulmonary resuscitation?
AB - Witnessing the attempted resuscitation of a loved one is likely to be traumatic
and distressing. However, because the majority of patients requiring
cardiopulmonary resuscitation (CPR) die, this raises the question, within the
hospital environment, of whether relatives should be invited to be present. There
is a distinct lack of nursing research available on this subject, particularly
with regard to the possible long-term effects on relatives. Much of the
information is anecdotal and focuses on the positive aspects of this practice.
With particular reference to the intensive care unit (ICU), the discussion in
this paper includes not only family presence during CPR from the perspective of
the patient, relatives and healthcare professionals, but also the potential legal
implications. Recommendations for nursing practice are offered.
PMID- 10196913
TI - Patients' experience of being critically ill or severely injured and cared for in
an intensive care unit in relation to the ICU syndrome. Part I.
AB - The intensive care unit (ICU) syndrome is regarded principally as a complex
interaction of several contributory factors, all of which can be seen as partly
responsible for the development of the syndrome. The purpose of this study was to
describe and give a deeper insight into patients' experiences and memory recall,
both during and after their stay in the ICU. Nineteen patients who had been
respirator treated (ventilated), and had stayed at least 36 hours in the ICU,
were interviewed about one week after discharge, and again 4-8 weeks after their
discharge from the ICU. Patients' experiences are interpreted and related to
previous views held concerning the syndrome, together with an awareness of other
important and significant phenomena, i.e. a hermeneutic approach. This study
partly confirms the findings of earlier studies concerning the ICU syndrome, but
also reveals some new aspects, which have not previously been considered. The
patients described themselves as experiencing some sort of state of chaos
following the onset of their sickness, injury or accident, which resulted in
feelings of extreme instability, vulnerability and fear, often experienced as
prolonged inner tension. It was reported that even the most trivial events in
circumstances or routines could trigger changes-either an increase or decrease-in
patients' feelings of fear or inner tension. The caring relationship was
perceived as providing an important degree of security and comfort. Nursing care
actions can therefore be seen as vital factors in patients overcoming the
accompanying horrific experiences to which they can be subjected. This state of
chaotic feeling, and how it is combated and treated, appear to be one critical
factor in the development and progression of the ICU syndrome.
PMID- 10196914
TI - Identifying the practice characteristics of advanced practitioners in acute and
critical care settings.
AB - This paper reports the results of a longitudinal, qualitative study into the role
transition of advanced nurse practitioners (ANPs) in the UK. Following the
completion of a Master's Degree in Health Studies programme, eleven ANPs working
in high-dependency and acute care settings completed a purpose-designed 'role
development diary' for the first six months they practised in their new role. In
the diary, ANPs recorded the nature and focus of practice activities, identified
the components of their practice perceived to be 'advanced', and documented the
factors that influenced role implementation and development. Once completed, the
diaries were subjected to a comparative analysis, which revealed that the level
of patient dependency and the type of clinical environment had a direct bearing
on the nature and extent of certain aspects of role performance. The findings
also indicated that, whilst practitioners identified multiple components in their
roles, priority was initially given to the acquisition and development of
technical and diagnostic skills. It was concluded that variations in the
performance of ANPs could be attributed not only to the nature of the clinical
environment, but prevailing personal, political and organizational agendas.
PMID- 10196915
TI - Analgesics in the management of chronic pain. Part four: Step 3 oral analgesic
drug therapy.
AB - Reluctance to commence treatment with a Step 3 drug on the Analgesic Stepladder
is a common reason for failure to manage chronic severe pain in many situations.
The fourth article in the series reviews the potent opioid analgesics for oral
use and in doing so addresses the various prejudices that surface when such
therapy is denied.
PMID- 10196916
TI - Extended hospitalization of medically stable children dependent on technology: a
focus on mutable family factors.
AB - This study identified three factors that influenced extended hospital stay in
medically stable children dependent on medical technology. A retrospective review
of 50 charts in a level II nursery was conducted. Bivariate analysis identified
factors contributing to extended stay: parental factors, societal factors, health
care factors, and presence of disease. Multiple regression explained 98% of the
variance in extended length of stay. Family factors accounted for 19.6%,
nonfamily factors accounted for 42.5%, and the two sets of factors together
accounted for an additional 35.9%. Family-related issues with a high potential
for change were identified. Pediatric providers should develop family
intervention strategies that identify the most appropriate level of care that
both advocates in the best interest of the child and family and contains the
rising cost of health care.
PMID- 10196917
TI - Test or trauma? The voiding cystourethrogram experience of young children.
AB - Many diagnostic procedures, while necessary and appropriate, may be experienced
by a child as a trauma. Health care professionals often perceive invasive
procedures such as surgery and needle biopsies as more painful and threatening to
the child than "test" such as voiding cystourethrograms (VCUGs). However,
clinical experience indicates that the VCUG is often perceived by children as
more highly distressing than other procedures. Success and a sense of competence
(or shame and doubt) in mastering challenging life experiences, such as medical
procedures, contribute to a child's evolving self-concept (Harter, 1983). These
memories and successful behaviors can be applied to future similar situations.
Health care professionals are challenged to help the child and the parents
through the procedure with minimal distress in an effective and efficient manner.
A series of vignettes illustrating parents' and children's experiences with a
VCUG procedure highlight the impact of the VCUG on children's coping ability and
adjustment. Recommendations for developmentally appropriate clinical practice
standards of care related to the VCUG procedure in young children also are
presented. Preparation as an ongoing partnership process among children, parents,
and health care professionals.
PMID- 10196918
TI - Facilitating the transition of adolescents with chronic conditions from pediatric
to adult health care and community settings.
AB - This article provides an overview of the health care issues and concerns of
adolescents with special health care needs and disabilities who are in transition
from pediatric to adult health care settings. Adolescents and their families face
numerous challenges in accessing adult health care providers who can give
adequate primary and specialized health care services to this growing population
of youth. Navigating the myriad new and unfamiliar adult services available can
be overwhelming for adolescents, their families, and pediatric providers.
Assessment and intervention strategies are described that can be used by the
pediatric nurse to facilitate successful transitions to adult health care and
community-based services.
PMID- 10196919
TI - Pneumatic otoscopy: a review of the literature.
AB - Pneumatic otoscopy is a universally recommended method of diagnosing otitis media
by detecting the presence of a middle ear effusion and hypomobility of the
tympanic membrane. This review presents a synthesis of the existing research on
the value of pneumatic otoscopy as a diagnostic tool. A literature search from
1987 to 1997 produced 11 applicable research articles. In five studies, which
compared pneumatoscopy with myringotomy, the mean sensitivity score was 89% and
the mean specificity score was 80%. In the only study of clinical use of
pneumatic otoscopy, 21% of respondents always used it, while 42% never used it as
part of their routine examinations. Education level of the examiner had no affect
on the value of pneumatoscopic findings. Pneumatic otoscopy is an important
diagnostic tool available to all health care providers, but replication of these
studies is essential to support these results. Furthermore, research is needed to
quantify its actual application on the clinical level.
PMID- 10196920
TI - Some challenges for mental health nurses in 1999.
PMID- 10196921
TI - Mental health nursing in the 21st century.
AB - Mental health nursing in the 21st century will expand to include a
neuropsychiatric focus that encompasses the science, knowledge, and skills of
both neurology and psychiatry. The shift to neuropsychiatric nursing is directed
by the explosion of knowledge in the neurobiologic basis of mental illness,
tremendous advances in diagnostic technology, and the discovery of new and more
effective psychopharmacologic treatments. Neuropsychiatric disorders are common,
disabling, costly, and stigmatizing. A neuropsychiatric paradigm allows treatment
to reach more people who are affected and is less stigmatizing than a
psychosocial view alone. Neuropsychiatric advanced practice nurses will need both
primary care and specialty knowledge and skills. The challenge to nursing
education is to determine how best to incorporate this knowledge and skills into
curricula. Neuropsychiatric research must focus on both biologic and behavioral
measures and interventions. The philosophical and ethical challenge to nursing is
to integrate biologic and behavioral concepts into the nursing care of mentally
ill people while remaining centered in the nursing domain and maintaining our
focus on caring and our sensitivity to the human condition.
PMID- 10196922
TI - "We may be different, but we are still nurses": an exploratory study of drug and
alcohol nurses in Australia.
AB - The problems experienced by generalist nurses in providing care to patients who
abuse alcohol and other drugs have been acknowledged in the literature. Despite
the demonstrated success of educational programs in improving attitudes and
enhancing the confidence of nurses in dealing with this clientele, the problem
remains. Although large numbers of nurses specialize in the care of patients with
drug- and alcohol-related problems, their specific skills have not been well
researched. This article reports on a qualitative research project undertaken
with 6 nurses currently practicing in a drug and alcohol unit in metropolitan
Victoria, Australia. The findings suggest that these nurses are very skilled in
their area of practice, and they can potentially provide information and support
to nurses from other areas. This liaison role can help minimize the negative
experiences frequently encountered by nonspecialist nurses caring for patients
with drug- and alcohol-related problems.
PMID- 10196923
TI - Distressed and stress resistant nurses.
AB - This study examines the relative contribution of personality, coping, and family
support to adaptation to stress in nursing. The sample (N = 1,043, mean age =
33.8 years) were nurses from three large public hospitals in Singapore. The
findings indicated that stress resistant nurses who adapted to high work stress
with good mental health status as measured by the General Health Questionnaire
(GHQ-12) developed by Goldberg (1972) had a higher self-esteem and were more
internal in locus of control than the distressed nurses who reported poor mental
health status under high work stress. The use of negative emotion focused coping
was less frequent among the stress-resistant nurses who also had greater supports
from family relationships. Discriminant function analysis revealed that
behavioral coping (e.g., enhancement of ability and physical health) had greater
contribution to stress resistance than cognitive coping (e.g., acceptance of
situations or change of perspectives). The findings were discussed with reference
to the high level of performance demanded by nursing.
PMID- 10196924
TI - Facilitating empowerment groups: dismantling professional boundaries.
AB - The purpose of this study was to identify the issues and the process faced by
public health nurses facilitating empowerment groups with people with a chronic
and persistent mental illness. Five public health nurses facilitated seven groups
which met weekly for a period of one year. Nurses kept field notes following each
group session and methods of grounded theory were used to develop an
understanding of the process of facilitating empowerment groups. A process of
dismantling professional boundaries was identified which included three
dimensions: experiencing the clash of worlds; joining the lives of people with a
mental illness; and an exploration of professional self. The results highlight
the need to challenge traditional ways of practicing.
PMID- 10196926
TI - Nephrology and the Internet.
PMID- 10196925
TI - Life events and psychological well-being in women sentenced to prison.
AB - There have been no systematic analyses of the factors that influence the
development of psychological well-being in women sentenced to prison. This study
identified relationships among life events, coping resources, and psychological
well-being (indicated by the absence of anxiety and depression). A descriptive
correlational design was used in a convenience sample of 62 incarcerated female
offenders. The respondents were in their early 30s, single, unemployed, and
receiving financial support from a variety of sources. They reported an average
of 10 life events in the 12 months preceding incarceration and accumulated an
average of 354 life change units. A positive correlation between the number of
life events and depression was identified (r = .24, p < .05). The women in this
study had high levels of depression as measured by the Center for Epidemiologic
Studies Depression Scale (L. Radloff, 1977; M = 31) and anxiety as measured by
the State-Trait Anxiety Inventory (C. D. Spielberger, 1983; M = 46). Nursing
interventions to reduce psychological distress at the time of admission to a
correctional facility may reduce feelings of loss, inadequacy, and powerlessness
that the women might otherwise have to endure.
PMID- 10196927
TI - Hepatitis B vaccine as a cause of false positive hepatitis B surface antigen.
AB - The hemodialysis unit at The Toronto Hospital routinely vaccinates its patients
against hepatitis B using Engerix B Hepatitis B Vaccine (Recombinant). A new
positive hepatitis B surface antigen (HBsAg) was flagged by the lab, but upon
investigation it was discovered that the patient had received hepatitis vaccine
two days earlier. The infectious diseases service was consulted and the case was
referred to the microbiologist. Subsequent testing showed a conversion to
negative antigen. We decided to test other patients who had just been vaccinated
to see if we could replicate our results. Seven other patients were selected, and
we found the incidence of false positive HBsAg to be 50%. The duration of the
vaccine-induced positive HBsAg lasted no more than two weeks. Our results are
compatible with the results found in the current literature.
PMID- 10196928
TI - The use of group process in the education of renal patients and families: a multi
centred collaborative approach.
AB - As health care systems are redefined in the 1990s, and as resources decrease,
group work is effective as an intervention. Social workers from three acute care
hospitals utilized group process as the primary theoretical framework to develop
a four-week education/support program for renal patients and families. In
collaboration with other health care team members, program format and content
were defined within a group development model. In addition, an understanding of
the adjustment process, and educational and emotional needs of group participants
were inherent in the planning. Interdisciplinary team members from three centres
shared responsibility for the agenda which created greater investment and
ownership. Evaluation of the program incorporated patient and family feedback
from each session and, as a result, content was further developed and refined.
This collaborative approach has become a standard component of renal care in the
community. However, the integrity of each centre's nephrology program has been
maintained. This article describes an educational program for renal patients and
families which was developed collaboratively by three nephrology programs. Data
collected from 1993 to 1997 have been incorporated.
PMID- 10196929
TI - A writing workshop for the CANNT Journal.
AB - Writing for publication requires special skills and understanding. The aim of
this workshop held by the co-editors of the CANNT Journal was to help
participants identify the first steps needed to initiate the process of writing
for publication. During the workshop, the attendees were invited to join small
groups with a facilitator for each group. The individual groups identified what
they considered to be their first five steps to writing for publication. This
information from each group was shared with all the attendees. At the end of the
session, helpful tools to aid potential authors were identified and thoughts on
future writing workshops were discussed.
PMID- 10196930
TI - Calciphylaxis: one hospital's experience.
AB - The lives of the ESRD population have been enhanced and prolonged by improved
conservative management, efficient dialysis and successful transplantation.
However, practitioners are noting some significant morbidity in these long-term
surviving nephrology patients. Clinical signs of renal osteodystrophy can be very
subtle and insidious. Bone pain, muscle weakness, and pruritus can be vague
symptoms. Calciphylaxis, which is classified as a skin disorder is an extremely
rare, painful, and progressive complication. Typically, the patient presents with
vascular calcifications, cutaneous ulcerations and tissue necrosis. The treatment
regimen for bone disease in the ESRD population will be reviewed. The symptoms of
calciphylaxis, diagnostic tests and prognosis will be discussed. Four case
studies describe our recent experience. Emphasis will be on the intense
multidisciplinary care required for this devastating and often fatal syndrome.
PMID- 10196931
TI - The value of communication through the use of a newsletter.
PMID- 10196932
TI - How does volunteerism develop?
PMID- 10196933
TI - Enhancing research participation and retention for three ethnically diverse
groups.
AB - Many researchers naively assume that the methods and research approaches that are
useful with European-Americans can also be used with minority populations. Little
attention has been paid to the development of culturally appropriate research
procedures and a discussion of the limitations of traditional research
methodologies. In this article I include the experiences and suggestions for
successfully conducting research with minority populations.
PMID- 10196934
TI - Cultural competence for nurses: canonical correlation of two culture scales.
AB - As the diversity of the US residential population increases, healthcare
professionals need to recognize the importance of culturally competent care on
health outcomes of individuals and communities. The purpose of this descriptive
correlational pilot study (N = 51) was to describe the relationship among scores
and sub-scores on scales measuring concepts of cultural competence. An additional
purpose was to develop reliability and validity data on each of three culture
scales for the population of hospital based registered nurses. Each of the scales
had previously reported reliability and validity data but were administered to
populations potentially different from southern-based, hospital-employed RNs. A
large medical center located in Southeastern US was chosen as the study's site
due to its diverse staff and client base. The Giger and Davidhizar Transcultural
Assessment Model and Theory was the theoretical foundation for the study and
Cultural Self-Efficacy Scale (CSES), Cultural Attitude Scale as developed by
Bonaparte (1977, 1979) and modified by Rooda (1990, 1992) (CAS-Modified), and
knowledge base questions (Rooda, 1990) were the chosen instruments. For this
group of hospital based RNs, the reliability analysis--scale (Alpha) for the 58
item CSES was .9778. The reliability analysis (Alpha) for the 22 knowledge base
questions was .6038 and .6412 for the 40 item CAS-M. Canonical correlation
analysis was performed between a set of attitude variables and a set of self
efficacy variables using SPSS (1995). Both sets of variables demonstrated
statistically significant relationships (at an a priori alpha of .05) to each
other (with an approximate Eta squared value for practical significance of .336),
providing sufficient evidence to reject the non-relationship null hypothesis. For
this sample and for these data, cultural self-efficacy toward Asian, Black,
Hispanic clients, and self-efficacy regarding nursing skills when caring for
diverse clients related to cultural attitudes and cultural self-efficacy. Nursing
care, cultural health beliefs, and cultural health attitudes related to attitudes
toward care of diverse clients. Both sets of variables related to each other as
qualities of culturally competent nursing care.
PMID- 10196935
TI - Voices from an Afghan community.
AB - A major role of the community health nurse is advocating to meet the needs of
population groups. This article describes how community health nurses utilized
two assessment tools, a windshield survey, a semi-structured interview protocol,
and the Healthy People 2000 National Health Objectives to collect pertinent
information and recommend program strategies at the primary, secondary and
tertiary prevention levels to reduce the prevalence of domestic violence in an
Afghan community.
PMID- 10196936
TI - An innovative approach for affirming cultural diversity among baccalaureate
nursing students and faculty.
AB - "Cultural Diversity" has become the buzz word of the nineties. The United States
has become the most culturally diverse nation in the world. Since there is no
arena where cultural diversity is more critical than health care, it is
imperative that nursing students and faculty become comfortable with the issues
surrounding the delivery of culturally competent care. The University of Southern
Mississippi has developed an innovative program with a dual purpose: (a) to
provide an environment of mutual understanding and respect for people of
different cultures; and (b) to provide a comfortable environment where minority
students can be valued and nurtured.
PMID- 10196937
TI - Workforce diversity and cultural competence in healthcare.
AB - This paper presents a discussion of workforce diversity in healthcare and its
attendant requisite of cultural competency. The first section of the paper argues
that self-assessments and diversity training are integral to workforce diversity
management. This paper maintains that diversity training should be a part of
overall strategic goals, and that the development of management goals should be
based on self-assessments. The second section of the review offers a framework of
cultural competency in healthcare delivery based on the relationship between
patient and provider, and the community and health system. For this relationship
to be successful, this review argues that health systems should foster providers
that can also be cultural brokers. The cultural broker role is seen as core to
achieving cultural competency.
PMID- 10196938
TI - Accessing spirituality.
PMID- 10196940
TI - American Cancer Society Oncology Professor named.
PMID- 10196941
TI - Spiritually connecting.
PMID- 10196939
TI - Connecting spiritually.
PMID- 10196942
TI - Web of vulnerability: Women In Street Prostitution.
PMID- 10196943
TI - Teaching breast self-examination to homeless women.
PMID- 10196944
TI - The need for tuberculosis education in the homeless male population.
PMID- 10196945
TI - Advanced nursing degree essential for future.
PMID- 10196947
TI - Student perspective: "I have a dream!".
PMID- 10196946
TI - Spiritual assessment of leadership.
PMID- 10196948
TI - Pursuit of a dream.
PMID- 10196949
TI - From stumbling blocks to stepping stones.
PMID- 10196950
TI - Building a viable infrastructure for ESRD risk contracting. Gambro nephrology
partners, renal care network of Florida show positive results. Part II.
PMID- 10196951
TI - Rediscovering method II as a reimbursement option.
AB - Recent discussions within the renal community confirm the following: we are in an
evolving health care environment that obliges us to review reimbursement
opportunities that promote patient care, contain costs, and maximize revenues.
This article will look at a sometimes overlooked option--Method II reimbursement
for home dialysis patients--as a way for dialysis facilities to work within the
established rules to both benefit patients and the overall dialysis program.
PMID- 10196952
TI - Rehabilitation as an essential social work function: A study of LORAC exemplary
practice winners. Life Options Rehabilitation Advisory Council. Part I.
PMID- 10196953
TI - Nutritionists in the renal care setting: an NN&I survey. Part I.
PMID- 10196954
TI - What makes the ideal dialysis setting?
PMID- 10196955
TI - Immunizing the ESRD patient population: providers face challenges.
PMID- 10196956
TI - A teaching tool for managing hemodialysis vascular access failure. Part II.
PMID- 10196957
TI - Strategies for influencing outcomes in pre-ESRD and ESRD patients.
PMID- 10196958
TI - 1998 U.S. Renal Data System Report/Part II. Living unrelated donor rate grew 46%
annually from 1993-96; hospitalizations higher for pediatric HD vs. PD patients.
PMID- 10196959
TI - Quality care organizations collaborate on performance measurement activities.
PMID- 10196961
TI - 1999 ESRD marketplace.
PMID- 10196960
TI - NKF public policy office emphasizes state initiatives.
PMID- 10196962
TI - PREP and profiles. Setting up a team for professional development.
PMID- 10196963
TI - Education for practice. Competence: an outcome-based approach as a model for
practice.
PMID- 10196965
TI - Understanding statistics. 5. ANOVA and linear regression.
PMID- 10196964
TI - Primary Care groups. Using health profiling as a tool for needs assessment.
PMID- 10196966
TI - Open learning. Complementary therapies and research.
PMID- 10196967
TI - PREP and profiles. The educational needs of nursing home nurses.
PMID- 10196968
TI - Education in practice. Learning to work with social workers.
PMID- 10196969
TI - On the job. Child health in the community.
PMID- 10196970
TI - Clinical supervision. Can nurse managers supervise?
PMID- 10196971
TI - Personality, and forces that influence behaviour.
PMID- 10196972
TI - Learning in clinical practice: 4. Developing competence.
PMID- 10196973
TI - What's the point of ... clinical governance?
PMID- 10196974
TI - Employing older nurses.
PMID- 10196975
TI - Divided loyalties.
PMID- 10196976
TI - Operation zero tolerance.
PMID- 10196977
TI - What is clinical governance?
PMID- 10196978
TI - Some patients can be awful.
PMID- 10196979
TI - Nursing education should be as much about self-development as about fact
cramming.
PMID- 10196980
TI - Make me welcome to your world.
PMID- 10196981
TI - The difference a day makes.
PMID- 10196982
TI - A day to remember, or perhaps best forgotten.
PMID- 10196983
TI - Mended knee.
PMID- 10196984
TI - The good and the bad of day surgery.
PMID- 10196985
TI - Great expectations.
PMID- 10196986
TI - Look before you leap.
PMID- 10196988
TI - Face to face. Interview by Eileen Fursland.
PMID- 10196987
TI - So you want to be an ... osteopath.
PMID- 10196989
TI - Dutch courage.
PMID- 10196991
TI - Ethics.
PMID- 10196990
TI - May name is Joe....
PMID- 10196992
TI - Libraries on the Internet.
PMID- 10196993
TI - The share index.
PMID- 10196994
TI - Basic powers under the Mental Health Act.
PMID- 10196995
TI - Cancer-stress link: the truth.
PMID- 10196996
TI - Pressure for evidence.
PMID- 10196997
TI - A&E nurses and alcohol-related attendances.
PMID- 10196998
TI - High time for justice.
PMID- 10196999
TI - Public misery, private profit.
PMID- 10197000
TI - Culture club.
PMID- 10197001
TI - A change of mind.
PMID- 10197002
TI - Removal of sutures.
PMID- 10197003
TI - Reuniting education and practice: new perspectives for a new age.
PMID- 10197005
TI - Regaining lost ground.
PMID- 10197004
TI - Dilemmas in mandatory reporting of domestic violence: carative ethics in
emergency rooms.
AB - Laws are clear when it comes to reporting child abuse, elder abuse, or
maltreatment of the disabeled; however, the fuzzy area of domestic violence, or
injury to women by their husbands or intimates, puzzles the system ethically and
legally. Experts are divided on the issue of mandatory reporting of domestic
violence by health care professionals. As exemplified by the Florida law, the
crux of the problem may be twofold. First, the law requires reporting of certain
incidents that are ambiguously defined. Second, reporting may be mandatory
without the patient's consent. Many experts in the field of domestic violence
suggest that mandated reporting by health care workers is not in the best
interests of the victims; it may lead to more violence and increase the victim's
reluctance to get needed health care. This victim vulnerability creates ethical
dilemmas in the emergency department, often the first outside contact after a
violent incident. This paper examines the implications of reporting applied to
emergency practice in the context of basic ethical standards. The application of
mandatory reporting laws to competent adult victims presents questions related to
nonmaleficence, beneficence, autonomy, confidentiality, and a variety of
contextual issues that arise from these main ethical domains.
PMID- 10197006
TI - Factors in job satisfaction of the psychiatric clinical nurse specialist.
AB - This exploratory descriptive study examines variables that affect the job
satisfaction of psychiatric clinical nurse specialists (CNSs). A convenience
sample of 52 psychiatric CNSs revealed a moderate amount of job satisfaction as
indicated on the Mueller/McCloskey Satisfaction Scale. CNSs employed outside
hospitals and those who had a private practice component to their jobs had
greater mean job satisfaction than those who were employed in the hospital
setting and did not have a private practice besides this work (p = 0.0188).
Hospital executives are urged to look at the structures of their organizations to
enhance the job satisfaction of these advanced nurses who work in a hospital.
PMID- 10197007
TI - The ethics of long-distance intercessory prayer.
PMID- 10197008
TI - Behaviorism to humanism: the case for philosophical transformations in nursing
education.
AB - Collaborative learning processes and problem-based learning methods facilitate
critical thinking capabilities for nurses practicing in multidisciplinary
settings. Nursing education, as well as that of other healthcare providers,
traditionally has been based on behaviorist educational theory. Massive economic
and cultural shifts, and the nationwide movement toward community-based
healthcare environments will mandate broad changes for structuring the
philosophical framework for nursing education. Humanistic collaborative learning
methods are proposed to meet the needs of preparing the next century of nursing
care professionals.
PMID- 10197009
TI - The effects of personal and environmental factors on health behaviors of older
adults.
AB - The purpose of this study was to examine the effects of personal factors, self
esteem and functional health and environmental factors, social support and
resource availability, on health behaviors of older adults. The interaction
effects of personal and environmental factors on health behavior were also
examined. Self-reported survey data were collected from a sample of 120 subjects.
Results of multiple regression analysis indicated that the combination of
personal and environmental factors explained 13% of the variance in health
behaviors for the older adult sample population. Resource availability and
functional health made significant independent contributions to the explanation.
Adding variables to represent the interaction of social support and functional
health and the interaction of social support and self-esteem significantly
increased the explained variance in health behavior (to 24%) for older residents
of resource-poor environments.
PMID- 10197010
TI - Critical thinking: linking assessment data and knowledge.
AB - A vital element of the assessment process is critical thinking; that is, linking
assessment data to knowledge. Making links or constructing knowledge is difficult
for students because of the complex skill and cognitive load that the assessment
process generates and because of students' limited view of the clinical
environment. Viewing learning from the cognitive psychological perspective
provides insight into knowledge construction and offers suggestions for faculty
who teach nursing students.
PMID- 10197011
TI - Nutrition in pregnancy: why is it important for the baby?
PMID- 10197012
TI - Primary care groups: a new opportunity for nurses.
PMID- 10197013
TI - Managing diabetes in children and adolescents: 1.
PMID- 10197014
TI - Skin problems and parasites in children: 3--Head lice.
AB - Head lice are common in children, occur occasionally in women and are rare in
men. All social classes are affected. Treatment should be reserved for genuine
cases of infestation, i.e. where live lice are seen. More research is needed into
methods of treating head lice. The school nurse has an important role in
educating children, parents and school staff.
PMID- 10197015
TI - Autism: recognising the signs in young children.
AB - Autism is an organic disorder affecting several areas of a child's development.
Autism is present from birth, or very soon after, but the nature of the disorder
can mean that diagnosis is delayed for months for years. Early intervention can
improve long-term function and help the families. Babies with autism may display
characteristic features of gaze, hearing, social development and play. Nurses
working with babies and young children are in a prime position to recognise these
characteristics and refer the family for specialised assessment. Learning
disabilities may or may not be present in children with autism. Always listen to
the parents. They often suspect something is wrong even though they may not be
able to be precise.
PMID- 10197016
TI - Life as a student health visitor.
PMID- 10197017
TI - One-to-one midwifery care at the Wessex Maternity Centre.
AB - Independent midwifery practice can offer women greater choice, flexibility and
more personalised care than may be available in NHS maternity units. The Wessex
Maternity Centre offers continuity of care through paired caseloading by
midwives. If women need to go into hospital, there is an arrangement whereby
their midwife goes with them and continues to provide care in hospital. 50% of
clients at the Centre are primiparae. The Centre's midwives have their own
clinical protocols based on up-to-date research and practice.
PMID- 10197018
TI - Helping brain injured children and their families.
AB - For many brain injured children, whether the injury is congenital or the result
of subsequent illness or accident, there is little to be done to put right the
underlying problem. Treatment programmes, however, can encourage better motor and
cognitive function and better nutrition. NHS continuing care for brain injured
children is under-resourced, often amounting to only half an hour of
physiotherapy fortnightly or even monthly. The British Institute for Brain
Injured Children (BIBIC) is a registered charity which exists to help families
with a brain injured child to learn to apply simple, practical, inexpensive
treatment programmes themselves, in their own homes. Initial assessments and
training take place at the BIBIC Centre in Somerset. Families are asked to
contribute towards costs if they are in a position to, but treatment does not
depend on ability to pay. Treatment sessions often last about 30 minutes and
families may be advised to carry out two or more sessions every day. Telephone
help and continuing support is available from BIBIC, and families are encouraged
to retain contact with their GP and hospital consultants, and local services.
PMID- 10197019
TI - Face up to acne.
PMID- 10197020
TI - Iron deficiency anaemia in the under-5s: how should we tackle it?
PMID- 10197021
TI - Osteoporosis in pregnancy: more than postural backache.
AB - Though uncommon, osteoporosis can occur in pregnancy or shortly after delivery.
The most common feature is back pain, often severely disabling. Suspect
osteoporosis if pain of sudden onset in the upper lumbar or thoracic spine is not
relieved by simple analgesia, or if there is a noticeable loss of height. X-rays
reveal low bone density and fractures of the vertebrae. 70% of cases occur in
first pregnancies. Recurrence is unusual. Most cases resolve spontaneously; a
minority cause disability lasting months or years. If osteoporosis is diagnosed,
breast feeding should be discouraged because of its effect on bone mineral
density. Anyone who has had osteoporosis of pregnancy is at risk of
postmenopausal osteoporosis and should take medical advice.
PMID- 10197022
TI - Recent developments in infant formulae: 1--The addition of LCPs.
AB - Long chain polyunsaturated fats (LCPs) are important components of membranes in
the human brain and retina. Preterm babies require a dietary source of LCPs, and
all preterm formulae in the UK are currently supplemented with LCPs.
Supplementation of term infant formulae with AA and DHA has resulted in apparent
improvements to visual and cognitive functioning in bottle-fed babies. These
improvements may be temporary and more research is needed to determine whether
these differences remain in the longer term.
PMID- 10197023
TI - Recognising meningococcal meningitis and septicaemia.
PMID- 10197024
TI - Reducing child accidents: lessons from down under.
AB - Home visits by public health nurses with knowledge of accident prevention
strategies can reduce hazards to children. Several areas in Australia are
developing "safe communities" in response to a WHO project. In several towns the
public health nurse delivers age-related safety information to families during
routine contacts. Health visitor education in the UK is falling to respond to the
challenge of reducing the main cause of death in children aged 1-4 years because
it is not giving practitioners adequate preparation for accident prevention work.
PMID- 10197025
TI - Quality, clinical governance and nurse prescribing.
PMID- 10197026
TI - The changing US health care system: challenges for responsible public policy.
AB - The "managed care backlash" arguably topped the list of media and policy concerns
in 1998. Yet, against the background of the highly charged environment in which
the future of our health care system continues to be debated, there is a dearth
of concrete, "objective" facts on the nature of the changes, the reasons for
them, and their meaning. An analysis of five important themes that emerged from a
review of the recent literature on health system change concludes that an
inherent tension exists between the interest in rapidly driving down health care
costs through organizational change and the long time frames that are required to
make fundamental changes in structure, process, and orientation. Unfortunately,
in an environment in which purchasers are driven to seek cost savings and the
political will supports a pluralistic and mixed public/private system, the health
system may chart an alternative course, with the result that purchasers may rely
increasingly on individual cost sharing and continue to cut back the amount of
coverage they are willing to offer. The real challenge for public policy makers
is to confront the issues directly, avoiding political incentives to adopt easy
and fast solutions for these complex matters.
PMID- 10197027
TI - The case of disability in the family: impact on health care utilization and
expenditures for nondisabled members.
AB - Families with a disabled member undergo heightened emotional and financial
stress, which can arise from caring for the person with one or more disabilities
over the life course or at the end of life. Because health care resources are
strained by the needs of the disabled family member, nondisabled members are
often limited in health care access and utilization when they are most in need of
care. This analysis uses the National Medical Expenditure Survey to describe
families with disabled members, based on multiple definitions of disability, and
to examine health care utilization and expenditures by nondisabled family
members. Indications of higher use of medical care by adult, nondisabled members
of such families support the frequent reports in the literature of stress
occurring in these situations. The signals of a household rationing effect for
families near and at poverty levels should alert policy makers to consider the
needs of the whole family when creating or modifying assistance programs.
PMID- 10197028
TI - Five laws for integrating medical and social services: lessons from the United
States and the United Kingdom.
AB - Because persons with disabilities (PWDs) use health and social services
extensively, both the United States and the United Kingdom have begun to
integrate care across systems. Initiatives in these two countries are examined
within the context of the reality that personal needs and use of systems differ
by age and by type and severity of disability. The lessons derived from this
scrutiny are presented in the form of five "laws" of integration. These laws
identify three levels of integration, point to alternative roles for physicians,
outline resource requirements, highlight friction from differing medical and
social paradigms, and urge policy makers and administrators to consider carefully
who would be most appropriately selected to design, oversee, and administer
integration initiatives. Both users and caregivers must be involved in planning
to ensure that all three levels of integration are attended to and that the
borders between medical and other systems are clarified.
PMID- 10197029
TI - Innovation and public accountability in clinical research.
AB - For more than 20 years, clinical researchers have expressed alarm about the
decline of their field, but they have failed to achieve a consensus on policies
to revitalize and sustain it. Although they have traced the plight of clinical
research to profound changes in science, medicine, and public expectations, their
conservative vision and preference for short-term measures inhibit effective
policy formulation. These trends are the outcome of historical developments, and
they seem to mandate a new approach to public policy. A potential source for more
viable and socially accountable policies lies in practitioners' notion that
clinical research bridges basic and applied science (by translating scientific
innovations into practical measures). Exploiting that idea, however, would
require a major reorientation of the field toward health services research and
the institutions that are struggling to support it.
PMID- 10197030
TI - Carnitine palmitoyltransferase: a viable target for the treatment of NIDDM?
AB - Inhibition of fatty acid oxidation is well recognized as a potentially effective
mechanism for controlling glycemia in non-insulin-dependent diabetes mellitus
(NIDDM). However, a direct targeting of inhibition of the intramitochondrial beta
oxidation pathway or an indirect modulation of fatty acid oxidation by inhibition
of substrate release from adipose stores has been fraught with lack of efficacy,
unacceptable side-effects or both. Focus has therefore recently been directed
towards the carnitine palmitoyltransferase (CPT) system, a three-component system
necessary for the transfer of long-chain fatty acids into the intramitochondrial
matrix. This article will briefly review the background for fatty acid oxidation
inhibition in NIDDM and then focus on the progress in the biological
understanding and drug discovery targeting of the CPT system for the treatment of
NIDDM. Based upon the review, it is concluded that mechanism-based hepatic and
myocardial toxicities in normal animals and a potential for a lack of human
efficacy may pose insurmountable hurdles for the development of CPT inhibitors
for the treatment of NIDDM.
PMID- 10197031
TI - Gastroprotective agents for the prevention of NSAID-induced gastropathy.
AB - Over 30 million people in the world take non-steroidal anti-inflammatory drugs
(NSAID's). A large percentage of these individuals will develop gastric ulcers
and related complications, a condition known as "NSAID gastropathy". NSAID
gastropathy differs from classic peptic ulcer disease in many ways, and
traditional peptic ulcer therapy is largely ineffective in preventing NSAID
induced gastropathy. The prostaglandin misoprostol has been shown to be effective
and is approved for the prevention of NSAID gastropathy. However, misoprostol has
side effects that limit its general use. For this reason, considerable effort
throughout the 1990's has focused on the identification of new gastroprotective
molecules. Some synthetic studies have been aimed at the preparation of new
prostaglandins, prostacyclin mimetics, and thromboxane antagonists. New histamine
H2 receptor antagonists have also been developed which, unlike cimetidine or
ranitidine, now appear to couple true gastroprotective activity with
antisecretory properties. One new H2 antagonist, ebrotidine, has shown clinical
utility in preventing NSAID gastropathy. Many other types of structures
(flavonoids, peptides, terpenoids, xanthines, others), as well as compounds
displaying certain pharmacological actions (5-hydroxytryptamine receptor binding,
adrenergic receptor binding, mast cell stabilization, others) have been linked in
some way to gastroprotection. This article reviews many of these recent
gastroprotection findings, with emphasis on those of potential use for prevention
of NSAID gastropathy.
PMID- 10197032
TI - Animal models of atherosclerosis and interpretation of drug intervention studies.
AB - Atherosclerosis has often been defined as a multifactoral disease; however, a
common risk factor associated with accelerated vascular disease in man or animals
is an elevated plasma cholesterol level. Even though there is no one perfect
animal model that completely replicates the stages of human atherosclerosis,
cholesterol feeding and mechanical endothelial injury are two common features
shared by most models of atherosclerosis. The models may differ with respect to
degree of dietary cholesterol supplementation, length of hypercholesterolemia,
dietary regimen and type, duration and degree of mechanical endothelial injury.
With the advent of genetic engineering, transgenic mouse models have supplemented
the classical dietary cholesterol induced disease models such as the cholesterol
fed hamster, rabbit, pig and monkey. The desire to limit the progression of
atherosclerosis has spawned numerous drug intervention studies. Biochemical as
well as morphologic and morphometric changes in the extent, structure and
composition of atherosclerotic lesions following drug intervention have become
major endpoints of in vivo drug intervention studies. Interpretations of
alterations in vascular pathology following drug administration are often
confounded by associated changes in plasma lipids and lipoproteins, limitation of
the animal models and additional properties of compounds unrelated to their
primary mode of action. Thus, the current review will summarize the pathology of
atherosclerosis, describe various animal models of vascular disease and provide a
critical review of the methods utilized and conclusions drawn when evaluating
pharmacologic agents in animals.
PMID- 10197033
TI - High density lipoprotein: are elevated levels desirable and achievable?
AB - In this review we focus on addressing two questions concerning high density
lipoproteins (HDL). First, are elevated levels of HDL a desirable clinical plasma
endpoint and secondly, if so, can strategies be devised that would allow the
identification of agents to elevate HDL. To address the first question we briefly
review the human epidemiologic and prospective data that identifies HDL as a risk
factor for coronary heart disease (CHD). To introduce HDL elevating strategies,
we next provide a brief review of the structural and enzymatic features of HDL
followed by a discussion on the current thinking of the metabolic origin of the
lipoprotein. We then turn to discussions on the key plasma and cell associated
proteins involved in the synthesis, catabolism, and remodeling of HDL by
analyzing data derived from human mutations, genetically engineered animal models
with altered HDL metabolism and in vitro experimental systems. Lastly, we propose
approaches to raise HDL that are either based on identification of small organic
molecules or more unconventional approaches such as gene therapy or delivery of
biologicals into plasma. This last section is based on an evaluation of the
putative mechanism of actions of both old and new HDL elevating compounds. Our
review concludes with an optimistic view that agents can be identified which may
have promise in the treatment of human hypoalphalipoproteinemia and CHD.
PMID- 10197034
TI - Selective estrogen receptor modulators (SERMs).
AB - Naturally occurring estrogens, such as 17 beta-estradiol and estrone, have
traditionally been thought to play a central role in the development and
maintenance of the female reproductive system and secondary sexual
characteristics. In recent years, their beneficial effects on the skeleton, the
cardiovascular system, and the central nervous system, as well as the cancer
risks associated with long term exposure have also been recognized. The
widespread use of "antiestrogens" such as tamoxifen for the prevention and
treatment of breast cancer has revealed that such compounds, while functioning as
estrogen antagonists in mammary tissue, actually mimic the effects of estrogen in
other tissues. The search for more selective agents has led to the development of
raloxifene, a Selective Estrogen Receptor Modulator, which functions as an
estrogen antagonist in the breast and uterus and as an estrogen agonist in the
skeleton and cardiovascular system. Recent progress in the development of SERMs
is the subject of this review, with an emphasis on structure activity
relationships and on their effects in non-traditional target tissues.
PMID- 10197035
TI - The fluorinated quinolones.
AB - Following the discovery of nalidixic acid in 1962, numerous structural
modifications have been made to the quinolone nucleus to increase antimicrobial
activity and improve pharmacokinetic performance. A major advance occurred during
the 1980's with the discovery that a fluorine at position-6 conferred broad and
potent antimicrobial activity, (e.g. norfloxacin) but still with relatively less
activity for Gram-positive and antiaerobic organisms than Gram-negative bacteria.
Subsequent developments produced quinolones with further improvements,
predominantly in either solubility (e.g. ofloxacin), antimicrobial activity (e.g.
ciprofloxacin) or prolonged serum half-life (e.g. pefloxacin). Recent
modifications have attempted to achieve an optimal blend of favourable properties
together with minimal potential for undesirable side-effects. The mode of action
of quinolones is by blocking of the bacterial enzyme gyrase. This enzyme is
responsible for the coiling and supercoiling of the DNA within the cell. When
this enzyme is inhibited, DNA transcription, which results in protein synthesis,
and DNA replication, which results in cell division, are inhibited. Improvements
in antimicrobial activity combined with adequate blood and tissue concentrations
do offer expectancy of enhanced therapeutic efficacy for new derivatives in those
infections by organisms which are 'marginally' sensitive to currently used
quinolones. The possibility of resistance emerging in these organisms during
treatment should also be reduced.
PMID- 10197036
TI - Recent developments in tetracycline antibiotics.
AB - The rapid emergence of pathogenic bacteria resistant to tetracyclines and other
currently available antibiotics has caused serious concern among medical
professionals. It has heightened resurgent interest in studying the mechanisms of
resistance and in developing new antibiotics. A comprehensive review has outlined
the developments of tetracyclines prior to 1980 [47]. This review will highlight
the pertinent advances in the tetracycline field during the last two decades,
including recent progress on elucidating the mechanisms of resistance, and the
development of novel tetracyclines to combat bacterial resistance. Most of the
new tetracycline derivatives described in this review have been either prepared
semisynthetically or isolated from fermentation. In the semisynthetic area,
efflux inhibitors that are effective in an in vitro model have been identified. A
new class of tetracyclines, named glycylcyclines has been the subject of numerous
reports, and will be the major focus of this review. The glycylcyclines are
currently the only derivatives that exhibit antibacterial activity comparable to
that of the early tetracyclines when they were first introduced. These compounds
show potent activity against a broad spectrum of Gram-positive and Gram-negative
bacteria, including strains that carry the two major tetracycline-resistance
determinants, efflux and ribosomal protection. Two of the glycylcycline
derivatives. DMG-MINO and DMG-DMDOT, have been studied by several groups of
investigators against a large number of clinical pathogens isolated from various
sources. The spectrum of activity of these compounds includes organisms with
resistance to antibiotics other than tetracyclines, e.g., methicillin-resistant
staphylococci, penicillin-resistant streptococcus pneumoniae, and vancomycin
resistant enterococci. Their in vitro, as well as in vivo activity against
bacteria with characterized tetracycline- or minocycline-resistant elements will
be summarized. The structure-activity relationships of glycylcyclines and their
mode of action will also be discussed.
PMID- 10197037
TI - Inhibitors of bacterial signal peptidases.
AB - Signal peptidases are serine endoproteinases responsible for the proteolytic
removal of N-terminal amino acid signal sequences from pre-secretory proteins in
all cellular lifeforms including bacteria. The demonstrated essentiality of the
enzymatic activity and the ubiquitous occurrence in bacteria, coupled with the
significant molecular differences between bacterial signal peptidases and those
of eukaryotes, define these enzymes as potential molecular targets for the
development of novel antibacterial agents. Few compounds are known to inhibit
bacterial signal peptidases and the most significant advance in SPase inhibition
has been the discovery of penem systems as time dependent irreversible
inhibitors. They are thought to act via acylation of the active site serine.
SPases are only acylated by the 5S penem stereochemistry, a stereochemical
preference mirrored in other azetidinone containing inhibitors. The implications
of this is that the active site serine of SPases approach their substrate from
the opposite side of the peptidic backbone to that of all other serine protease
families whose structures are known. The activity of penems is significantly
enhanced by the incorporation of a C6 hydroxyethyl substituent, thought to bind
into the S1 pocket of the enzyme. Penem inhibition of SPases has been
demonstrated in vitro, in isolated enzyme assays, and in vivo in pulse-chase
assays.
PMID- 10197038
TI - Recent developments in streptogramin research.
AB - The streptogramins are a class of antibiotics remarkable for their antibacterial
activity and their unique mechanism of action. These antibiotics are produced
naturally, but the therapeutic use of the natural compounds is limited because
they do not dissolve in water. New semisynthetic derivatives, in particular the
injectable streptogramin quinupristin/dalfopristin, offer promise for treating
the rising number of infections that are caused by multiply resistant bacteria.
The streptogramins consist of two structurally unrelated compounds, group A and
group B. The group A compounds are polyunsaturated macrolactones: the group B
compounds are cyclic hexadepsipeptides. Modifications of the group B components
have been mainly performed on the 3-hydroxypicolinoyl, the 4
dimethylaminophenylalanine and the 4-oxo pipecolinic residues. Semi-synthesis on
this third residue led to the water-soluble derivative quinupristin. Water
soluble group A derivatives were obtained by Michael addition of aminothiols to
the dehydroproline ring of pristinamycin IIA. Followed by oxidation of the
intermediate sulfide into the sulfone derivatives (i.e., dalfopristin). Water
soluble derivatives (both group A and group B) can now be obtained at the
industrial scale. Modified group B compounds are now also being produced by
mutasynthesis, via disruption of the papA gene. Mutasynthesis has proved
particularly useful for producing PIB, the group B component of the oral
streptogramin RPR 106972. The streptogramins inhibit bacterial growth by
disrupting the translation of mRNA into protein. Both the group A and group B
compounds bind to the peptidyltransferase domain of the bacterial ribosome. The
group A compounds interfere with the elongation of the polypeptide chain by
preventing the binding of aa-tRNA to the ribosome and the formation of peptide
bonds, while the B compounds stimulate the dissociation of the peptidyl-tRNA and
may also interfere with the release of the completed polypeptide by blocking its
access to the channel through which it normally leaves the ribosome. The synergy
between the group A and group B compounds appears to result from an enhanced
affinity of the group B compounds for the ribosome. Apparently, the group A
compound induces a conformational change such that B compound binds with greater
affinity. The natural streptogramins are produced as mixtures of the group A and
B compounds, the combination of which is a more potent antibacterial agent than
either type of compound alone. Whereas the type A or type B compound alone has,
in vitro and in animal models of infection, a moderate bacteriostatic activity,
the combination of the two has strong bacteriostatic activity and often
bactericidal activity. Minimal inhibitory concentrations of
quinupristin/dalfopristin range from 0.20 to 1 mg/l for Streptococcus pneumonae,
from 0.25 to 2 mg/l for Staphylococcus aureus and from 0.50 to 4 for Enterococcus
faecium, the principal target organisms of this drug. Quinupristin/dalfopristin
also has activity against mycoplasmas, Neisseria gonorrhoeae, Haemophilus
influenz, Legionella spp. and Moraxella catarrhalis. Bacteria develop resistance
to the streptogramms by ribosomal modification, by producing inactivating
enzymes, or by causing an efflux of the antibiotic. Dimethylation of an adenine
residue in rRNA, a reaction that is catalyzed by a methylase encoded by the erm
gene class, affects the binding of group B compounds (as well as the macrolides
and lincosamides; hence, MLSB resistance), but group A and B compounds usually
maintain their synergy and their bactericidal effect against MLSB-resistant
strains. erm genes are widespread both geographically and throughout numerous
bacterial genera. Several types of enzymes (acetyltransferases, hydrolases) have
been identified that inactivate the group A or the group B compounds. Genes
involved in streptogramin efflux have so far been found only in staphylococci,
particularly in coagulase-negative species
PMID- 10197039
TI - Cytotoxics derived from distamycin A and congeners.
AB - Distamycin A is an antibiotic, characterised by an oligopeptidic pyrrolocarbamoyl
frame ending with an amidino moiety, which binds reversibly to DNA minor groove
with high selectivity for TA-rich sequences and shows antiviral and antiprotozoal
activity. Distamycin was used as DNA sequence selective vector of alkylating
functions, leading to a substantial increase of cytotoxicity in comparison to
that, very weak, of distamycin itself. The benzoyl nitrogen mustard derivative of
desformyldistamycin, tallimustine, was selected as a candidate antineoplastic
drug in view of its strong activity against a series of experimental tumors.
Tallimustine, like distamycin, shows DNA selective binding to TA-rich sequences
but its cytotoxicity is not associated with DNA strand breaks and interstrand
crosslinking, at variance with classical phenyl nitrogen mustards. Tallimustine
represents an important model for the design of new minor groove alkylating
agents derived from distamycin and analogues, including the so-called
lexitropsins, sequence-reading oligopeptides in which one or more N-methyl
pyrrole units of distamycin are replaced by imidazole or other rings. The
structural features of the alkylating moieties and binding frames, the antitumor
activities and the mechanism of action of most representative cytotoxics derived
from distamycin and congeners are discussed. Some of these, recently reported,
show an activity profile apparently superior to tallimustine. Finally, a concise
survey of representative hybrid compounds in which known non-alkylating cytotoxic
agents or their active moieties have been tethered to distamycin and congeners is
presented and briefly discussed. These compounds witness the attention paid to
this approach on the basis of the interest for the DNA binding features of
distamycin A.
PMID- 10197040
TI - A redox pathway leading to the alkylation of nucleic acids by doxorubicin and
related anthracyclines: application to the design of antitumor drugs for
resistant cancer.
AB - Doxorubicin has been a constituent of antitumor drug protocols for a broad
spectrum of cancers for more than two decades. Side effects and resistance
continue to be important limitations. Drug targets responsible for both side
effects and anti-tumor activity are cell membrane receptors, cell membrane
lipids, nucleic acids and topoisomerase. Induction of oxidative stress is
responsible for most if not all biological activity. An important consequence of
oxidative stress is the production of formaldehyde which can subsequently be
utilized by the drug for covalent bonding to nucleic acids and other targets as
shown by in vitro experiments. Multidrug resistance mechanisms inhibit drug
induced DNA damage, drug uptake, and drug-induced oxidative stress. Synthetic
anthracyclines conjugated to formaldehyde circumvent some if not all of the
resistance mechanisms. Consequently, anthracycline-formaldehyde conjugates have
potential for the treatment of resistant cancer.
PMID- 10197041
TI - Recent progress in the development of tubulin inhibitors as antimitotic antitumor
agents.
AB - Tubulin protein is a major target of drug molecules, and consequently, tubulin
inhibitors have attracted great attention as antimitotic antitumor agents for
chemotherapeutic use. Hundreds of synthetic or semisynthetic tubulin inhibitors
have been discovered and developed recently that are related to the natural
products colchicine, vinblastine, and taxol. Representatives include
allothiocolchicinoids, vinorelbine, and taxotere. This review will describe the
recent progress being made in the development of novel antimitotic antitumor
tubulin inhibitors. The emphasis has been placed on related research in the
author's laboratory, including development of colchicine derivatives and other
colchicine binding site drugs, such as flavonoids and quinolone derivatives.
Syntheses and modifications of novel compounds, biological activity evaluation,
and structural activity relationships will be discussed as well. Further research
will undoubtedly lead to the discovery of additional tubulin inhibitors that have
potential for use as anticancer drugs.
PMID- 10197042
TI - Heterocyclic analogs of DNA minor groove alkylating agents.
AB - It is generally accepted that neoplastic transformation is related to genes
alteration or oncogene activation. In particular, DNA minor groove binding drugs
have been extensively studied through the years in order to influence the
regulation of gene expression by means of specific interactions with DNA bases
moieties. Pyrrolo[2,1-c],[1,4].benzodiazepines (PBDs), CC-1065 and distamycins
are three classes of minor groove binders which showed interesting cytotoxicity
profiles, refined through already reviewed processes of SAR studies. Among the
modifications to the three families of antitumor compounds, heterocyclic
substitutions have been extensively applied by many groups in order to either
modify the reactivity profile or introduce extra interactions within the minor
groove, thus changing the binding site or modulating the binding sequence. The
updated material related to these modifications has been rationalised and ordered
to offer an overview of the argument.
PMID- 10197043
TI - The protein kinase ABC's of signal transduction as targets for drug development.
AB - Signal transduction plays a key regulatory role in the growth and metastatic
potential of tumor cells. These signaling pathways form an interconnecting grid
that serves to regulate the homeostatic, survival and invasive functions of the
cell. Among the key regulatory molecules in these pathways are the
serine/threonine-protein kinases A, B, and C, also known respectively as cyclic
AMP-dependent protein kinase (PKA), Akt (PKB) and protein kinase C (PKC). These
protein kinases modulate pathways associated with tumor proliferation, cell
survival and multidrug resistance, and at a molecule level are likely to serve as
effective targets for drug design. The unique structural features of each protein
kinase have been deduced from their crystallographic structures and form unique
opportunities for structure-based drug design. In addition, these protein kinases
are potentially important targets for antisense oligonucleotide therapy, and
therefore may provide a means of selectively inhibiting tumor proliferation and
inducing apoptosis with minimal nonspecific cytotoxicity.
PMID- 10197044
TI - New approaches to rapid onset antidepressants.
AB - The challenges for the design of new antidepressant drugs are threefold: rapid
onset of antidepressant response, broader efficacy, and fewer adverse effects.
While progress has been made to reduce side-effects, the currently available
drugs show no convincing evidence for a shorter delay of onset nor for improved
efficacy. This review summarizes some of the hypotheses that try to explain the
delayed onset and that are currently used for antidepressant drug design. These
approaches include combinations of SSRI activity with either NA reuptake
inhibition or 5-HT1A-, 5-HT2-, or alpha 2-adrenergic receptor specificity, as
well as targeting interactions with specific receptor subtypes (5-HT1A, 5-HT1A/5
HT2, 5-HT1B/D, alpha 2/5-HT2, D2/D3). Structure activity relationship studies to
obtain molecular entities with the desired pharmacological profile are discussed.
Many structural modifications have exploited successfully the acquired knowledge
on structural features that are necessary for monoamine reuptake inhibition as
well as for affinities at various receptors. Most of the current drug design
efforts are focused on these approaches, which are based on the monoamine theory
of depression; however, novel biological concepts of depression involving other
receptor systems or intracellular targets are briefly mentioned. Although their
impact on the onset of antidepressant response is only a matter of speculation at
this moment, they may lead to the identification of targets for truly novel
antidepressants.
PMID- 10197045
TI - Oleamide: an endogenous sleep-inducing lipid and prototypical member of a new
class of biological signaling molecules.
AB - Oleamide is an endogenous fatty acid primary amide that accumulates in the
cerebrospinal fluid under conditions of sleep deprivation and induces
physiological sleep in animals. A review covering its discovery, its
implications, and the emerging biology surrounding its discovery is presented.
Consistent with its role as a prototypical member of a new class of biological
signaling molecules, enzymatic regulation of endogenous concentrations of
oleamide have been characterized or proposed. Fatty acid amide hydrolase (FAAH)
is an integral membrane protein that degrades oleamide and potent inhibitors with
physiological sleep-inducing properties have been disclosed. The
characterization, cloning, and neuronal distribution of FAAH have been detailed
and the enzyme was found to possess the ability to hydrolyze a range of fatty
acid amides including anandamide which serves as the endogenous ligand for the
cannabinoid receptor. An additional endogenous substance with REM sleep-inducing
properties, 2-octyl gamma-bromoacetoacetate, was characterized as a potent FAAH
inhibitor. Oleamide has been shown to modulate serotonergic neurotransmission and
inhibit intercellular gap junction communication and detailed studies of its well
defined and selective structural features required for activity have been
disclosed.
PMID- 10197046
TI - The inhibitory glycine receptor: prospects for a therapeutic orphan?
AB - The inhibitory glycine receptor is a member of the ligand-gated ion channel
superfamily. It mediates inhibitory synaptic transmission in mammalian spinal
cord and brainstem. Structure and function of the receptor, as well as its
chromosomal localization and genetic structure, have been extensively studied.
While hereditary and acquired receptor dysfunctions can be identified, selective
and specific modulation of receptor function is still lacking. The preponderance
of current literature regarding the inhibitory glycine receptor raises the
prospect that adequate methods for the treatment of glycine receptor-mediated
disorders might be developed.
PMID- 10197047
TI - Therapeutic approaches to the treatment of neuroinflammatory diseases.
AB - Microglia cells are present in the central nervous system and respond quickly to
pathogenic stimuli in order to protect the brain. When these immunological
responses activate inappropriately or are prolonged, they can contribute to the
neuronal damage observed in many neurodegenerative diseases. A variety of immune
system modulators including complement proteins, inflammatory cytokines such IL-1
alpha, IL-1 beta, IL-3, IL-6, TNF-alpha, and S100 beta, colony-stimulating factor
1, coagulation proteins and matrix metalloproteases are made by both microglia
and astrocytes. Additionally astrocytes, the predominant glial component of the
brain, express cell-adhesion molecules, cytokine receptors and induce nitric
oxide synthease. The pathophysiology of Alzheimer's disease, stroke, traumatic
brain injury, and multiple sclerosis suggest that a large portion of the
irreversible damage observed can be attributed to a neuroinflammatory mechanism.
The immunomodulators of these diseases are reviewed and new agents within
specific molecular mechanisms are presented and discussed.
PMID- 10197048
TI - Central control of feeding behavior by neuropeptide Y.
AB - Obesity is a serious health problem in the Western societies, therefore its
treatment has become the subject of intense interest in the scientific community.
A significant number of recent publications enlist different central and
peripheral factors which play important roles in the regulation of food intake,
body weight and energy expenditure. Neuropeptide Y, a 36 amino acid peptide,
which is quite abundant in the brain, seems to be one of the more important
players in these regulations. Recently five NPY receptors have been cloned and
pharmacological evidence strongly supports the existence of a sixth receptor.
There are many contradictory findings regarding which NPY receptor mediates the
effect of NPY on food intake. This article will review the effects of NPY on the
regulation of food intake and energy expenditure and will discuss the
pharmacological and molecular evidence as to which NPY receptor(s) mediate this
effect. The review will also summarize the progress which has been made in the
design of novel NPY-ergic ligands, especially NPY receptor antagonists, for
potential use in the treatment of obesity.
PMID- 10197049
TI - Discovery of ascomycin analogs with potent topical but weak systemic activity for
treatment of inflammatory skin diseases.
AB - Drug therapy for the major inflammatory skin diseases, which include atopic
dermatitis, psoriasis and allergic contact dermatitis, is often inadequate due to
poor efficacy, toxicity, or both. Much research has focused on the macrolactam T
cell inhibitors as a promising new class of agents for immunotherapy, and
medicinal chemistry efforts to design novel ascomycin analogs have produced
clinically promising agents. A synthetic program to modify the ascomycin nucleus
to alter its physicochemical properties and promote systemic clearance is
described. A biologic screening strategy to identify analogs with reduced
systemic activity and rapid pharmacokinetic elimination led to identification of
the clinical candidate, ABT-281. A swine contact hypersensitivity model was used
as a stringent indicator of skin penetration as human doses of topical
corticosteroids produced inhibition only in the 50% range and ED50 values were
100-fold less potent than in rat. Also, cyclosporine was confirmed to be
topically inactive in swine, as seen in human. ABT-281 had topical potency equal
to tacrolimus (FK506) despite a severalfold lower potency for inhibiting swine T
cells in vitro, consistent with superior skin penetration. ABT-281 was found to
have a shorter duration of action after i.v. dosing in monkeys using an ex vivo
whole blood IL-2 production assay. Systemic potency was reduced by 30-fold or
more in rat popliteal lymph node hyperplasia and contact hypersensitivity assays.
Following i.v. or i.p. administration in the swine contact hypersensitivity
model, ABT-281 was 19- and 61-fold less potent, respectively, than FK506.
Pharmacokinetic studies showed that ABT-281 had a shorter half life and higher
rate of clearance than FK506 in all three species. The potent topical activity
and reduced systemic exposure of ABT-281 may thus provide both efficacy and a
greater margin of safety for topical therapy of skin diseases.
PMID- 10197050
TI - Inhibitors of tryptase for the treatment of mast cell-mediated diseases.
AB - Human tryptase is a structurally unique and mast cell specific trypsin-like
serine protease. Recent biological and immunological investigations have
implicated tryptase as a mediator in the pathology of numerous allergic and
inflammatory conditions including rhinitis, conjunctivitis, and most notably
asthma. A growing body of data further implicates tryptase in certain
gastrointestinal, dermatological, and cardiovascular disorders as well. The
recent availability of potent, and selective tryptase inhibitors, though, has
facilitated the validation of this protease as an important therapeutic target as
well. Herein, we describe the design and potency of four classes of selective
tryptase inhibitors, of which the first three types are synthetic and the fourth
is natural in origin: 1) peptidic inhibitors (e.g., APC-366), 2) dibasic
inhibitors (i.e., pentamidine-like), 3) Zn(2+)-mediated inhibitors (i.e., BABIM
like), and 4) heparin antagonists (e.g., lactoferrin). These inhibitors have been
tested in the airways and skin of allergic sheep. Aerosol administration of
tryptase inhibitors from each structural class 30 minutes before, and 4 hours and
24 hours after allergen challenge, abolishes late phase bronchoconstriction and
airway hyperresponsiveness in a dose-dependent manner. Moreover, intradermal
injection of APC-366 blocks the cutaneous response to antigen. These studies
provide the essential proof-of-concept for the further pursuit of tryptase
inhibitors for the treatment of asthma, and perhaps other allergic diseases.
Results from clinical studies with the first generation tryptase inhibitor APC
366, currently in phase II trials for the treatment of asthma, provide additional
support for a pathological role for tryptase in this disease. Notable advances in
the area of tryptase inhibitor design at Axys Pharmaceuticals, Inc. include a
novel, zinc-mediated, serine protease inhibitor technology (described herein),
and the discovery of a unique class of extremely potent and selective dibasic
tryptase inhibitors. Independently, an X-ray crystal structure of active tryptase
tetramer complexed with 4-amidinophenyl pyruvic acid has been reported. It is
anticipated that these discoveries will further accelerate the design of
structurally novel tryptase inhibitors as well as the development of new drugs
for the treatment of mast cell tryptase-mediated disorders.
PMID- 10197051
TI - DR (MHC class II) ligands: an approach to rheumatoid arthritis therapeutics.
AB - The presentation of peptide antigens to T-cells by MHC Class II proteins is a
central process in cellular and humoral immune responses. Blockade of this
presentation event via synthetic ligands that bind to disease-associated MHCs
(such as DR1 and DR4) may be useful for the treatment of autoimmune diseases such
as rheumatoid arthritis, Type 1 diabetes, multiple sclerosis, lupus erthymatosis
and Graves disease. Recently reported synthetic ligands for DR1 and DR4 are short
modified peptides (2-7 mers) capable of competing at nanomolar concentrations
with antigenic peptides for the DR (MHC) binding groove.
PMID- 10197052
TI - Adenosine kinase inhibitors.
AB - Adenosine (ADO) is an endogenous modulator of intercellular signaling that
provides homeostatic reductions in cell excitability during tissue stress and
trauma. The inhibitory actions of ADO are mediated by interactions with specific
cell-surface G-protein coupled receptors regulating membrane cation flux,
polarization, and the release of excitatory neurotransmitters. ADO kinase (AK; EC
2.7.1.20) is the key intracellular enzyme regulating intra- and extracellular ADO
concentrations. Inhibition of AK produces marked increases in extracellular ADO
levels that are localized to cells and tissues undergoing accelerated ADO
release. Thus AK inhibition represents a mechanism to selectively enhance the
protective actions of ADO during tissue trauma without producing the nonspecific
effects associated with the systemic administration of ADO receptor agonists.
During the last 10 years, specific inhibitors of AK based on the endogenous
purine nucleoside substrate, ADO, have been developed. Potent AK inhibitors have
recently been synthesized that demonstrate high specificity for this enzyme as
compared to other ADO metabolic enzymes, transporters, and receptors. In both in
vitro and in vivo models, AK inhibitors have been shown to potently increase ADO
concentrations in a tissue and event specific fashion and to demonstrate
potential clinical utility in animal models of epilepsy, ischemia, pain, and
inflammation. AK inhibitors have demonstrated superior efficacy in these models
as compared to other mechanisms of modulating ADO availability, and these agents
exhibit reduced side-effect liabilities compared to direct acting ADO receptor
agonists. The preclinical profile of AK inhibitors indicate that these agents may
have therapeutic utility in a variety of central and peripheral diseases
associated with cellular trauma and inflammation. Clinical trials are currently
underway to evaluate the efficacy of AK inhibitors in seizure disorders and pain.
PMID- 10197053
TI - Genomics in the real world.
AB - The term genomics has evolved into a catch-all term for a variety of information
intensive biological methodologies. While the promise of genomics in the
bio/pharmaceutical industry is great, its impact on the drug discovery pipeline
has not yet been realized, excluding a few notable exceptions. As companies
acquire several years of experience in working with genomic data, it is likely
that the impact on the discovery process will slowly emerge as we learn to
integrate these new technologies into individual discovery programs. It is clear
that extracting novel biologically valid targets targets from exponentially
growing amounts of sequence data requires time and considerable investment in
biological research infrastructure. In order to accelerate the process of target
validation, a variety of functional genomics technologies are also being
developed to try to predict the effect of inhibitory compounds in advance of
development. Resources spent on early stage exploratory efforts such as these can
pay off by improving the success rate for screening and medicinal chemistry.
PMID- 10197054
TI - Cellular camouflage: fooling the immune system with polymers.
AB - Immunological recognition of foreign cells is a primary concern in both
transfusion and transplantation medicine. Our unique approach to this problem is
to globally camouflage the surface of the foreign cell using nonimmunogenic, long
chain polymers such as methoxypoly(ethylene glycol) [mPEG]. mPEG-modification of
red blood cells effectively attenuates both antibody binding to surface epitopes
and decreases the inherent immunogenicity of foreign, even xenogeneic red cells.
These cells exhibit normal structural and functional characteristicsin vitro and
exhibit normal in vivo survival in animal models. Pegylation of white blood cells
(particularly antigen presenting cells and T lymphocytes) surprisingly prevents
recognition of foreign class II molecules and prevents T cell proliferation in
response to foreign MHC molecules. Potential applications for the covalent
binding of nonimmunogenic, long chain polymers (e.g., PEG) to intact cells
include, but are not limited to: 1) derivatized RBC to diminish transfusion
reactions arising from sensitization to minor blood group antigens
(allosensitization) in the chronically transfused (e.g., sickle and thalassemia
patients); 2) use of mPEG modification of "passenger" lymphocytes to prevent
immune recognition and graft versus host disease; and 3) derivatization of the
vascular endothelium of donor tissues prior to transplantation to
prevent/diminish acute tissue rejection. In contrast to highly specific blocking
mechanisms (e.g., anti-CD4; proteolytic removal of RBC A/B antigens), the
generation of globally camouflaged (i.e., stealth) cells may more effectively
prevent the often complex and redundant events leading to immune recognition of
foreign cells.
PMID- 10197055
TI - Chymase: its pathophysiological roles and inhibitors.
AB - Chymase is a chymotrypsin-type serine protease mainly localized in mast cells
(MCs). Human, primate, and dog chymase generate angiotensin II (Ang II) from Ang
I, while mouse and rat chymases degrade Ang II. It is suggested that chymase
generating Ang II might be an alternative Ang II-forming enzyme to angiotensin
converting enzyme (ACE) in the renin-angiotensin system in tissues, but not in
blood, and cause hypertrophy and remodeling of cardiovascular tissues. Chymase
also degrades extracellular matrix, and processes procollagenase, inflammatory
cytokines and other bioactive peptides. As a result, chymase plays important
roles in inflammatory tissues through its proteolytic activities to cause tissue
remodeling, that is, a chymase inhibitor may have the ability to prevent diseases
caused by the above inflammatory reactions. The investigation of chymase
inhibitors by pharmaceutical companies has yielded peptide and peptide mimetic
inhibitors. We also found potent non-peptide low molecular inhibitors. However,
the in vivo functions of chymase have not been verified so far by applying a
chymase inhibitor to in vivo pathological models. In this article, we overview
the pathophysiological roles of chymase and chymase inhibitors proposed to date,
and discuss the structure-activity relationships of substituted 3-phenylsulfonyl
1-phenylimidazolidine-2,4-dione derivatives.
PMID- 10197057
TI - Dopamine-beta-hydroxylase inhibition: a novel sympatho-modulatory approach for
the treatment of congestive heart failure.
AB - Pre-clinical and clinical studies suggest that chronic sympathetic activation in
congestive heart failure (CHF) is a maladaptive response which accelerates the
progressive worsening of the disease. Consequently, therapeutic interventions
which inhibit sympathetic nerve function are likely to favorably alter the
natural course of the disease. Indeed, recent clinical studies have shown that
treatment with carvedilol, a beta-blocker, reduces mortality and the risk of
death and hospitalization. The therapeutic value of beta-blockers, however, may
be limited by their propensity to cause acute hemodynamic deterioration which
results from abrupt withdrawal of sympathetic support. Thus, although the
introduction of beta-blockers represents an important advance in the treatment of
CHF, a better tolerated means of modulating the sympathetic nervous system would
be highly desirable. An alternative strategy for directly modulating sympathetic
nerve function is to inhibit the biosynthesis of norepinephrine (NE) via
inhibition of dopamine-beta-hydroxylase (DBH), the enzyme which catalyzes the
conversion of dopamine (DA) to NE in sympathetic nerves. This approach may have
the following three merits over beta-blockade. First, this class of drugs would
be expected to produce gradual modulation, as opposed to abrupt blockade, of
sympathetic nerve function and, consequently, would not be associated with acute
hemodynamic worsening thereby obviating the need for dose-titration. Second, from
a theoretical standpoint, DBH inhibitors, at low doses, would preferentially
inhibit NE release in the heart since the storage pool of NE in this organ is
selectively depleted in CHF. Lastly, inhibition of DBH would augment the levels
of DA which, via agonism of dopamine receptors, could have beneficial effects on
renal function. Nepicastat is a novel, selective and potent (IC50 = 9 nM)
inhibitor of DBH. Preclinical studies have shown that nepicastal produces gradual
modulation of catecholamine levels (reduction in NE and elevation of DA and DA/NE
ratio) in cardiovascular tissues and plasma, attenuates sympathetically-mediated
cardiovascular responses and also has salutary effects on renal function. In a
canine heart failure model, normalization of transmyocardial norepinephrine
balance with nepicastat retards the process of ventricular dilation and prevents
progressive worsening of cardiac function. Early short-term clinical studies in
CHF patients have shown that nepicastat is well tolerated and produces
significant and dose-dependent increases in plasma DA/NE concentrations.
PMID- 10197056
TI - Quantitative structure-activity relationships of antiarrhythmic drugs.
AB - A Comprehensive review of quantitative structure-activity relationship (QSAR)
studies on antiarrhythmic agents is presented. From the discussion point of view,
the antiarrhythmic agents have been put into two broad classes: specific and
nonspecific. While the main members of the former class can be beta-adrenergic
blocking agents (beta-blockers), any chemical that can act directly on the
myocardial cell membrane, producing a cardiodepressant effect via changes in
basic electrophysiological properties of the membrane, such as automaticity,
excitability, conductivity, and refractoriness, has been put in the latter class.
QSARs exhibit that the biological actions of a variety of drugs belonging to any
class depend primarily on the lipophilic haracter of the molecule or
substituents. Thus, the hydrophobic interaction is found to play a dominant role
in the action of antiarrhythmic agents. In certain cases, the QSARs also exhibit
the role of electronic parameters, suggesting that certain receptors may have
electronic site also, permitting the drugs to involve in some electronic
interactions, too.
PMID- 10197058
TI - Is ceramide signaling a target for vascular therapeutic intervention?
AB - Today's society is plagued by cardiovascular diseases such as hypertension and
atherosclerosis. Research devoted to the study of these diseases has focused, in
part, on physiological phenomena responsible for the development and progression
of the disease. Peripheral vascular function is one such focal point of research,
and identification of cellular mechanisms that regulate vascular contractility
and/or cellular proliferation is crucial for the development of new therapeutic
interventions to combat these diseases. This review evaluates a new signaling
mechanism, the ceramide signaling pathway as a potential target for therapeutic
intervention. Special attention is given ceramide signaling in the contexts of
vascular reactivity and cell proliferation in the vasculature. While ceramide
signaling is a nascent area of vascular research, a growing body of evidence from
other physiological systems implicates this new pathway as a potential regulator
of contractile and cell proliferative functions within the blood vessel wall.
PMID- 10197059
TI - Recent advances in antihypertensive therapy.
AB - There are multiple different approaches that have been adopted in the past to
cure hypertension. Hypertension is a multifactorial disease frequently associated
with other cardiovascular problems. None of the antihypertensive drugs available
can cure all cases of hypertension. This situation causes a unique scenario in
this area of therapeutic research: less recent approaches, which make use of
drugs acting on the adrenergic system, diuretics, calcium antagonists, nitro
vasodilators and so on, have not yet been abandoned, while new compounds are
still being developed today. Newly acquired and more detailed knowledge of the
renin-angiotensin system, of the role of the endothelium and ionic channels in
the homeostasis of blood pressure has opened up new lines of study. There are
also a number of experimental compounds targeted for other action mechanisms
(phosphodiesterase inhibitors, neuropeptide Y antagonists, ouabain-like factor
antagonists), that could also represent innovative approaches to hypertension
therapy. Some hints regarding the current developments in the well established
and innovative categories of antihypertensives will be given in this review.
PMID- 10197060
TI - Prior collateral sprouting enhances elongation rate of sensory axons regenerating
through acellular distal segment of a crushed peripheral nerve.
AB - Regenerating axons in crushed peripheral nerves grow through their distal nerve
segments even in the absence of Schwann cell support, but their elongation rate
is reduced by 30%. We examined whether prior exposure of sensory neurons to
trophic factors achieved either by collateral sprouting or regeneration after
conditioning lesion could enhance subsequent regeneration of their axons after
crush, and compensate for loss of cell support. Collateral sprouting of the
peroneal cutaneous sensory axons in the rat was evoked by transection of adjacent
peripheral nerves in the hind leg. The segment of the peroneal nerve distal to
the crush was made acellular by repeated freezing. Sensory axon elongation rate
during regeneration was measured by the nerve pinch test. Prior axonal sprouting
for two weeks increased the elongation rate of sensory axons through the
acellular distal nerve segment back to normal value observed in control crushed
nerves. The number of axons in the acellular distal segment at a fixed distance
from the crush site was about 50% greater in sprouting than in control non
sprouting nerves. However, prior sprouting caused no further increase of axon
elongation rate in control crushed nerves. Prior collateral sprouting, therefore,
could in some respect compensate for loss of cell support in the distal nerve
segment after crush lesion. This suggests that loss of cell-produced trophic
factors is probably responsible for slower elongation rate through the acellular
distal nerve segment. Surprisingly, prior conditioning lesion caused no
enhancement of elongation rate of the sensory axons regenerating in the absence
of cell support.
PMID- 10197061
TI - Endoneurial microvasculature of chronically transected sciatic nerves in diabetic
rats.
AB - To characterize the morphology of the endoneurial microvasculature of
degenerating nerves under hyperglycemia, the morphology of endoneurial
microvessels in transected sciatic nerves was examined in normal and
streptozotocin-induced diabetic rats. Three months after transection, the
fascicular area and median vascular luminal area at the proximal level of the
distal stump were significantly larger in diabetic than in control animals,
whereas the number of vessels per fascicle was the same in the two groups.
Arterioles in various stages of development were found in the centrifascicular
region in some transected nerves. Serial sections revealed that these vessels
originated from transperineural arterioles. The frequency and magnitude of
vascular wall thickening were both greater in diabetic rats. These results
suggest that the endoneurial microvasculature responds abnormally to nerve injury
under hyperglycemia.
PMID- 10197062
TI - Mast cell-associated Renaut bodies in the peroneal nerve of a dog with a history
of mastocytosis.
AB - Multiple Renaut bodies were identified by light microscopy in the biopsied common
peroneal nerve of a dog with generalized neuropathy, hypothyroidism and a history
of cutaneous mastocytosis. In addition, numerous granulated cells were associated
with most of the Renaut bodies. Electron microscopic examination confirmed these
to be mast cells, both central and peripheral to Renaut bodies, a phenomenon
never previously reported. Endoneurial fibrosis, myelinated fiber loss, as well
as evidence of axonal degeneration, demyelination and remyelination were
observed. 'Vacuolation' of endoneurial fibroblasts was also present. The location
of these Renaut bodies in the common peroneal nerve, and the absence of any
documented or expected nerve compression, implicates other etiological factors.
These observations are the first to report an association between mast cells and
Renaut bodies. It is possible that mast cells, at least in this case, are
involved in the formation of Renaut bodies.
PMID- 10197063
TI - The stochastic diffusion models of nerve membrane depolarization and interspike
interval generation.
AB - The first step to make the theory of stochastic diffusion processes that arise in
connection with single neuron description more understandable is reviewing the
deterministic leaky-integrator model. After this step the general principles of
simple stochastic models are summarized which clearly reveal that two different
sources of noise, intrinsic and external, can be identified. Many possible
strategies of neuronal coding exist and one of these, the rate coding, for which
the stochastic modeling is relevant, is pursued further. The rate coding is
reflected, in experimental as well as theoretical studies, by an input-output
curve and its properties are reviewed for the most common stochastic diffusion
models. The results for the simplest stochastic diffusion model, the Wiener
process, are presented and from them strong limitations of this model can be
understood. The most common diffusion model is the Ornstein-Uhlenbeck process,
which is one substantial step closer to reality since the spontaneous changes of
the membrane potential are included in the model. Both these models are
characterized by an additive noise. Taking into account the state dependency of
the changes caused by neuronal inputs, we derive models where the noise has a
multiplicative effect on the membrane depolarization. Two of these models are
compared with the Wiener and Ornstein-Uhlenbeck models. How to identify the
parameters of the models, which is an unavoidable task for the models
verification, is investigated. The time-variable input is taken into account in
the last part of the paper. An intuitive approach is stressed throughout the
review.
PMID- 10197064
TI - Intraepidermal nerves in human skin: PGP 9.5 immunohistochemistry with special
reference to the nerve density in skin from different body regions.
AB - The intraepidermal nerves of normal adult human skin were demonstrated by
employing a powerful marker of neuronal elements, protein gene product (PGP) 9.5.
There were two types of epidermal nerves, free nerve endings and nerves in the
Merkel cell-neurite complex. The free nerve endings distributed to, and
terminated in, all the strata basale, spinosum and granulosum, and they appeared
as thin fibers, mostly varicose, branched or single processed, straight or bent.
They existed at every site of the human body, including face, trunk and
extremities. However, the densities of these nerves varied in different body
parts and areas. The number of nerves decreased from the trunk to the distal
parts of the limbs, and small denser 'innervation patches' showed up in the
epidermis which were identified in confocal microscopy as one morphologic
terminal field coming from the same dermal nerve bundle. This study has confirmed
the existence of epidermal nerves in normal adult human skin, and presented a
more clear picture than earlier. The difference between densities of epidermal
nerves at different body areas implies area-specific functions of the
intraepidermal nerve terminals. The observed intraepithelial nerve fibers may
have a pain-perceiving role, however, also trophic or immunoregulatory roles can
not be excluded.
PMID- 10197065
TI - Comparative analysis of numerical estimation methods of epithelial nerve fibers
using tissue sections.
AB - The proper assessment of neuron numbers in the nervous system during
physiological and pathological conditions, as well as following various
treatments, has always been an important part of neuroscience. The present paper
evaluates three methods for numerical estimates of nerves in epithelium: I)
unbiased nerve fiber profile and nerve fiber fragment estimation methods, II) the
traditional method of counting whole nerve fibers, and III) the nerve fiber
estimation method. In addition, an unbiased nerve length estimation method was
evaluated. Of these four methods, the nerve length per volume method was
theoretically optimal, but more time-consuming than the others. The numbers
obtained with the methods of nerve fiber profile, nerve fragment and nerve fiber
estimation are dependent on the thickness of the epithelium and the sections as
well as certain shape factors of the counted fiber. However for those, the actual
counting can readily be performed in the microscope and is consequently quick and
relatively inexpensive. The statistical analysis showed a very good correlation
(R > 0.96) between the three numerical methods, meaning that basically any method
could be used. However, dependent on theoretical and practical considerations and
the correlation statistics, it may be concluded that the nerve fiber profile or
fragment estimation methods should be employed if differences in epithelial and
section thickness and the nerve fibers shape factors can be controlled. Such
drawbacks are not inherent in the nerve length estimation method and, thus, it
can generally be applied.
PMID- 10197066
TI - Early onset cerebellar ataxia and preservation of tendon reflexes: clinical
phenotypes associated with GAA trinucleotide repeat expanded and non-expanded
genotypes.
AB - The aim of this study was to determine phenotypie characteristics of patients
with early onset cerebellar ataxia (EOCA) with preserved tendon reflexes. The
series comprises 25 patients, representing 10% of all ataxic patients who have
been genetically studied in our laboratory since 1990. There were 11 males and 14
females. Fourteen patients were homozygous for the GAA expansion on chromosome
9q13 (group 1) and therefore a diagnosis of Friedreich's ataxia with retained
reflexes (FARR) was given. The remaining 11 patients had two normal non-expanded
alleles (group 2) and a working diagnosis of EOCA with retained reflexes (EOCARR)
was established. Mean ages of onset were 13.7 +/- 5.9 years (3-25) for group 1
and 10.3 +/- 7.3 for group 2; the difference was not significant. Frequencies of
symptoms and signs were also comparable for both groups the only significant
differences being the higher frequency of nystagmus, cardiomyopathy and sensory
neuropathy in group 1 patients. There was a tendency for FARR patients to have
higher frequencies of hypopallesthesia in the lower limbs and skeletal
deformities. In none of the cases diabetes mellitus was observed. We conclude
that differentiation of FARR and EOCARR may be suspected by classical clinical
and electrophysiological data and confirmed by analysis of the GAA repeat.
PMID- 10197067
TI - Cutaneous silent period (CSP) in peripheral neuropathies represents the temporary
suppression of the intentional electromyographic activities.
PMID- 10197068
TI - Leptin: in search of role(s) in human physiology and pathophysiology.
PMID- 10197069
TI - Leptin and the thyroid--a puzzle with missing pieces.
PMID- 10197070
TI - Are all beneficial effects of growth hormone really beneficial?
PMID- 10197071
TI - A new chemiluminescent assay for the rapid detection of thyroid stimulating
antibodies in Graves' disease.
AB - OBJECTIVE: Thyroid stimulating antibodies (TSAb) are the cause of Graves' disease
(GD). At present, these antibodies can only be measured using bioassays, which
are generally time consuming and difficult to apply to whole serum. Here we
describe a new chemiluminescent assay for the detection of TSAb in serum samples.
METHODS: A Chinese hamster ovary (CHO) cell line, stably transformed with a
reporter plasmid containing the firefly luciferase gene under the transcriptional
control of multiple cAMP responsive elements (CRE), was transfected with the
human thyroid stimulating hormone (TSH) receptor. A clonal cell line, (NA-4), was
obtained which showed a dose-dependent increase in luciferase activity in
response to bovine and human TSH stimulation. NA-4 was subsequently used to study
TSAb activity in 42 GD sera. RESULTS: Of the GD sera 25 (60%) produced an
increase in luciferase activity of 1.4-9 fold that obtained with control sera.
Results were compared with an established bioassay for TSAb, based on the direct
measurement of intracellular cAMP, and there was a significant correlation
between the two assays (r = 0.8; P < 0.0001). IgG from GD patients, but not
controls, also increased luciferase activity in NA-4 cells using concentrations
as low as 3 mg/l in selected samples. CONCLUSION: The present report describes a
simple, sensitive and rapid assay for the detection of TSAb, with application
both in the clinical analysis of GD patient sera and as a potential research tool
for use in the isolation of TSAb monoclonal antibodies.
PMID- 10197072
TI - Leptin and the pituitary-thyroid axis: a comparative study in lean, obese,
hypothyroid and hyperthyroid subjects.
AB - OBJECTIVE: To study interactions between leptin and the pituitary-thyroid axis,
both in euthyroid and dysthyroid states. SUBJECTS AND MEASUREMENTS: We
investigated the relationships of plasma leptin to levels of free thyroid
hormones and TSH in 18 patients with newly diagnosed hyperthyroidism, 22 with
newly diagnosed primary hypothyroidism, and 32 lean (body mass index [BMI] < 30)
and 37 obese (BMI > 30 kg/m2) euthyroid subjects. Hypothyroid patients were
restudied during thyroxine replacement treatment. RESULTS: Median [interquartile
range] plasma leptin concentrations were highest in obese euthyroid subjects
(31.5 [19.0-48.0] and in untreated hypothyroid patients (19.2 [11.5-31.5]), and
lowest levels in untreated hyperthyroid patients (8.9 [5.5-11.1]) and lean
euthyroid control subjects (6.6 [3.9-14.4] micrograms/l (Kruskall-Wallis one-way
analysis of variance; P < 0.0001). In euthyroid subjects, plasma leptin levels
were higher in obese than in lean subjects (P < 0.00001). In obese subjects
plasma levels of TSH correlated with percentage body fat (r = 0.67; P < 0.001)
and plasma leptin (r = 0.61; P < 0.001). In untreated hyperthyroid subjects
plasma leptin was unrelated to free T3, and in untreated hypothyroidism plasma
leptin was unrelated to either free T3 or TSH concentrations (all P = NS). In
untreated hyperthyroid, but not hypothyroid, patients plasma leptin
concentrations correlated with BMI (r = 0.57; P = 0.02). Treatment of
hypothyroidism with thyroxine resulted in a significant reduction in plasma
leptin concentrations from 20.8 (11.8 to 31.6) to 12.9 (4.6-21.2) micrograms/l (P
= 0.005), but BMI did not change significantly in the hypothyroid subjects being
studied prospectively. CONCLUSIONS: (i) In euthyroid subjects, plasma leptin and
TSH levels correlate, and both are positively correlated with adiposity. (ii)
Plasma leptin was significantly elevated in hypothyroid subjects, to levels
similar to those seen in obese euthyroid subjects. (iii) Treatment of
hypothyroidism resulted in a reduction in the raised plasma leptin levels. The
data are consistent with the hypothesis that leptin and the pituitary-thyroid
axis interact in the euthyroid state, and that hypothyroidism reversibly
increases leptin concentrations.
PMID- 10197073
TI - The relationship between the serum leptin concentrations of thyrotoxic patients
during treatment and their total fat mass is different from that of normal
subjects.
AB - OBJECTIVE: Previous studies of leptin in thyrotoxic human subjects have been
short-term and cross-sectional. We have measured serum leptin concentrations in
thyrotoxic patients in order to study the influence of endogenous thyroid
hormones on the relationship between serum leptin and fat mass. DESIGN PATIENTS,
MEASUREMENTS: In 10 fasting thyrotoxic patients (8 females, 2 males, mean age: 51
years) we measured serum leptin (microgram/l), total thyroxine (TT4), total
triiodothyronine (TT3), thyrotropin (TSH) and by Dual Energy X-ray Absorptiometry
(DEXA) total fat mass (TFM, kg) at time of diagnosis (0 months, baseline) and
during 12 months treatment with thiamazole. For comparison 16 fasting thiamazole
treated euthyroid patients (14 females, 2 males, mean age: 38 years) were studied
after one year follow-up (26 months (15-48)) and 18 normal controls (12 females,
6 males, mean age: 39 years). RESULTS: The serum leptin concentration was 9.1
(1.3 micrograms/l (mean (SEM) in the thyrotoxic patients and increased
significantly to 16.0 (1.3 micrograms/l (P < 0.0005) after 12 months treatment
compared to both normal subjects and their own baseline. There was a significant
correlation between serum leptin concentration and TFM in the normal control
group (r = 0.79, P < 0.00009), in the thiamazole-treated euthyroid group (r =
0.85, P < 0.00003) and in the baseline thyrotoxic group (r = 0.84, P < 0.002) but
the serum leptin/TFM ratio increased significantly during 12 months of
antithyroid drug treatment from 0.34 (1.2 micrograms/l/kg to 0.53 (1.2
micrograms/l/kg (P < 0.03). CONCLUSION: The thiamazole-treated thyrotoxic
patients increased their serum leptin concentrations during 12 months antithyroid
drug treatment without a significant corresponding degree of changes in TFM as
expected from normal controls. It is suggested that the metabolic state in
thyrotoxic patients can influence the regulation of serum leptin concentrations
without any associated changes in TFM.
PMID- 10197074
TI - Growth hormone treatment improves body fluid distribution in patients undergoing
elective abdominal surgery.
AB - OBJECTIVE: To investigate the possible beneficial effects of growth hormone (GH)
in catabolic patients we examined the impact of GH on body fluid distribution in
patients with ulcerative colitis undergoing elective abdominal surgery. DESIGN
AND MEASUREMENTS: Twenty-four patients (14 female, 10 male) aged 19-47 years were
in a double-blinded study randomly assigned to receive either placebo (n = 12) or
GH (n = 12) 6 i.u. s.c. twice daily from 2 days before until 7 days after ileo
anal J pouch surgery. Extracellular and plasma volume (ECV, PV) were determined
using 82Br and 125I albumin dilution at day -2 and at day 7, and body composition
was estimated by dual X-ray absorptiometry and bioimpedance. Changes in body
weight and fluid balance were recorded and hence intracellular volume was
assessed. RESULTS: During placebo treatment body weight decreased 4.3 +/- 0.6 kg;
during GH treatment body weight was constant (P < 0.01). There was a positive
fluid balance in the GH-treated patients compared to the placebo group (GH: 3.6
+/- 0.7 l; plc: -0.7 +/- 1.2 l, P < 0.01). ECV increased 2.12 +/- 0.70 l during
GH and was unaffected during placebo (P = 0.02). PV was unchanged by GH and
decreased 0.39 +/- 0.08 l during placebo administration (P = 0.03). Intracellular
volume (ICV) decreased less during GH than during placebo (GH: -1.42 +/- 0.45;
plc: -3.70 +/- 0.76; P = 0.02). Bioimpedance remained constant during GH
administration and increased 60 +/- 9 ohm in the placebo-treated group (P <
0.05). Plasma renin and aldosterone remained unchanged in both study groups.
CONCLUSION: Body weight, plasma volume and intracellular volume is preserved
during GH treatment in catabolic patients and ECV is increased. From a
therapeutic point of view these effects may be desirable under conditions of
surgical stress.
PMID- 10197075
TI - Characterization of serum SHBG isoforms in prepubertal and pubertal girls.
AB - OBJECTIVE: SHBG is a circulating glycoprotein that binds dihydrotestosterone,
testosterone and oestradiol with high affinity and low capacity. In girls, serum
concentrations of SHBG gradually decrease with age due to a true fall in
concentration and not to a change in the binding characteristics. The aim of our
study was to determine the pattern of serum SHBG isoforms in normal girls in
early childhood (ECh), late childhood (LCh) and puberty (P). SUBJECTS: Fifteen
normal girls were studied. They were divided into three groups according to their
age: ECh: 3.7 +/- 0.9 years (mean +/- SD, n = 5); LCh: 6.4 +/- 0.5 years (n = 5);
and P: 13.4 +/- 1.5 years (n = 5). METHODS AND MEASUREMENTS: Preparative
isoelectric focusing was used to isolate SHBG isoforms according to their
isoelectric point (pI). Three groups of isoforms were isolated: SI: pI 5.2-5.4;
SII: pI 5.4-5.6 and SIII: pI 5.6-5.8. Steroid levels in serum were determined by
RIA. RESULTS: The relative distribution of SHBG isoforms (% of the total SHBG
recovered, mean +/- SD) in the three groups of girls studied was: ECh: SI: 25.8
+/- 9.9, SII: 53 +/- 10.5 and SIII: 21.2 +/- 1.6; LCh: SI: 8.8 +/- 3.1, SII: 58.8
+/- 12.2 and SIII: 31.8 +/- 8.6; P: SI: non-detectable; SII: 51.6 +/- 12.6 and
SIII: 48.4 +/- 12.6. CONCLUSION: These results indicate that serum SHBG is more
heterogeneous before puberty. A considerable proportion of acidic isoforms are
present early in life; they decrease during the prepubertal period and disappear
when sexual development is completed. After puberty the glycoprotein is more
homogeneous and an important proportion of more basic isoforms is present. At
puberty serum SHBG not only falls in concentration but also has an altered sialic
acid content which modulates its circulating half-life.
PMID- 10197076
TI - A cytotoxic T lymphocyte antigen-4 (CTLA-4) gene polymorphism is associated with
autoimmune Addison's disease in English patients.
AB - OBJECTIVE: Recent studies have demonstrated an association between a
microsatellite polymorphism of the CTLA-4 gene, specifically a 106 base pair
allele, and both Graves' disease and autoimmune hypothyroidism. The aim of the
present study was to determine whether the same polymorphism of the CTLA-4 gene
was associated with autoimmune Addison's disease. DESIGN AND PATIENTS: We
analysed a microsatellite polymorphism (variant lengths of a dinucleotide (AT)n
repeat) within exon 3 of the CTLA-4 gene in the following groups: 21 English
patients with non-associated Addison's disease, 18 with autoimmune polyglandular
syndrome type 2 (APS2) and 173 healthy control subjects; 26 Norwegian patients
with non-associated Addison's disease, 9 with autoimmune polyglandular syndrome
type 1 (APS1), 17 with APS2 and 100 controls; 3 Finnish patients with non
associated Addison's disease, 5 with APS2 and 71 controls; 10 Estonian patients
with non-associated Addison's disease, 2 with APS2 and 45 controls. MEASUREMENTS:
The CTLA-4 microsatellite gene polymorphisms were determined by polymerase chain
reaction amplification of genomic DNA and resolution of the products on
sequencing gels. RESULTS: The frequency of the 106 base pair allele was
significantly increased in the groups of English patients with either non
associated Addison's disease or APS2 (P = 0.02 and 0.04, respectively), when
compared to healthy controls with no clinical evidence or family history of
either Addison's disease or any other autoimmune disorder. For Norwegian patients
with either non-associated Addison's disease, APS1 or APS2, there was no
association (P = 0.69, 0.62 and 0.97, respectively). This was also the case for
Finnish patients with either non-associated Addison's disease or APS2 (P = 0.23
and 0.28, respectively) and for Estonian patients with either non-associated
Addison's disease or APS2 (P = 0.34 and 0.29, respectively). CONCLUSIONS: These
results indicate that differences exist in the frequency of the 106 base pair
allele in different population groups and in only the English population was the
106 base pair allele associated with Addison's disease.
PMID- 10197077
TI - The effect of past use of the injectable contraceptive depot medroxyprogesterone
acetate on bone mineral density in normal post-menopausal women.
AB - OBJECTIVE: Depot medroxyprogesterone acetate (DMPA), an injectable progestogen,
is a widely used contraceptive acting primarily by inhibiting secretion of
pituitary gonadotrophins, thus producing oestrogen deficiency. Cross-sectional
and prospective studies in pre-menopausal women have shown DMPA use to be
associated with reduced bone density, but bone density increases following
discontinuation of the drug. Because fracture rates are low in pre-menopausal
women, the principal concern arising from the effects of DMPA on bone is that
there may be residual osteopenia in former users such that their post-menopausal
fracture risk is increased. The present study addresses this question. DESIGN:
Cross-sectional study of bone density in post-menopausal former users of DPMA and
controls. SUBJECTS: Three hundred and forty-six normal post-menopausal women, of
whom 34 had previously used DMPA. The median age at which DMPA use began was 41
years and the median duration of use was 3.0 years. MEASUREMENTS: Bone density
was measured in the spine, proximal femur and total body by dual-energy, X-ray
absorptiometry. RESULTS: There were no significant differences in bone density at
any site between the women who had previously used DMPA and the others in the
cohort. However, in those who had used DMPA for > 2 years there was a trend
towards bone densities being lower in the former users, the differences from non
users being 1.6% in the lumbar spine (P = 0.6), 3.1% in the femoral neck (P =
0.4) and 0.5% in the total body (P = 0.8). There was no correlation between bone
densities and the duration of DMPA use, the age at discontinuation of DMPA, or
the time between DMPA discontinuation and the menopause. CONCLUSIONS: Any
residual effects of depot medroxyprogesterone acetate use on post-menopausal bone
density are small and therefore unlikely to have a substantial impact on fracture
risk in the post-menopausal years.
PMID- 10197078
TI - Clinical features associated with metastasis and recurrence of differentiated
thyroid cancer in children, adolescents and young adults.
AB - OBJECTIVE: Differentiated thyroid cancer (DTC), including papillary (PTC) and
follicular (FTC) variants, is unusual in children and accounts for only 10% of
all cases. For that reason, knowledge of the clinical features which predict
recurrence is limited. We reviewed 170 cases of childhood DTC to determine if
specific clinical or pathological findings were associated with increased risk of
recurrence. DESIGN: This was a retrospective study of children and adolescents
with DTC registered in the Department of Defense Automated Centralized Tumor
Registry. PATIENTS: We reviewed 137 cases of PTC and 33 cases of FTC diagnosed
between 1953 and 1996 at < or = 21 years of age. RESULTS: In the PTC group
(median follow-up 6.6 years, range 2 month-39.5 years), only one patient died,
but 21 developed local and 6 developed distant recurrence. By univariate
analysis, recurrence was more common in patients with multifocal (odds ratio 7.5)
or large tumours (odds ratio 4.1), and in those with palpable cervical
lymphadenopathy (odds ratio 3.0) or metastasis at diagnosis (odds ratio 2.8). By
multivariate analysis focality was the best predictor of recurrence (P = 0.0019).
In the FTC group (median follow-up 5 years, range 6 month-38.1 years), no patient
died of disease, but 5 developed recurrence. As with PTC, recurrence was more
likely in patients with multifocal tumours (odds ratio 22.0). CONCLUSIONS:
Differentiated thyroid cancer in children and adolescents has low mortality, but
a high risk of recurrence. Young patients with large, multifocal tumours that are
already metastatic at diagnosis have the greatest risk of recurrence.
PMID- 10197079
TI - Cytoplasmic staining of erbB-2 but not mRNA levels correlates with
differentiation in human thyroid neoplasia.
AB - OBJECTIVE: Amplification and overexpression of the erbB-2 proto-oncogene in human
carcinomas may have prognostic significance. Its role in thyroid carcinoma is
controversial. We investigated human thyroid tumours for erbB-2 gene
amplification, activating mutations in the transmembrane domain, quantitative
mRNA expression and protein expression. MATERIALS AND METHODS: DNA and mRNA were
extracted from 47 morphologically characterized, frozen thyroid tumours including
10 nodular hyperplasias, 3 follicular carcinomas and 34 papillary carcinomas (4
with tall-cell features, 2 with insular and 2 with anaplastic de
differentiation). DNA amplification was analysed by differential PCR. The
transmembrane domain of erbB-2 was sequenced in all tumours for activating
mutations in position 659. Levels of mRNA expression were determined by
competitive mRNA RT-PCR. Immunohistochemistry (IHC) for erbB-2 protein expression
in corresponding paraffin-embedded samples was evaluated. RESULTS: Our results
showed no DNA amplification of erbB-2. Sequencing of the transmembrane domain of
erbB-2 revealed no activating mutations. The level of mRNA expression was
variable, 11 papillary carcinomas showing statistically significant elevated mRNA
levels compared with corresponding normal thyroid tissue; however, this did not
correlate with other indicators of poor prognosis. In contrast to elevated mRNA
levels in tumours, the level of protein staining correlated with degree of
differentiation, normal and hyperplastic tissue being strongly positive and
poorly differentiated tumours negative. CONCLUSION: There are no mutations or
amplifications of the erbB-2 gene in human thyroid tumours. Elevated erbB-2 mRNA
expression in some thyroid tumours is not associated with clinical features of
poor prognosis; however, the significance of the elevated mRNA levels is unclear,
as it did not result in protein overexpression. Instead, cytoplasmic erbB-2
protein detection by IHC correlates with differentiation of human thyroid tumours
and may be a feature of good prognosis.
PMID- 10197080
TI - The relationship between the growth hormone and insulin-like growth factor axis
in long-term survivors of childhood brain tumours.
AB - OBJECTIVE: We compared IGF-1 and IGFBP3 concentrations in a group of adults
treated for brain tumours in childhood with those of matched controls, and
investigated the relationship between the GH secretory pattern and IGF-1/IGFBP3
concentrations in the entire group. DESIGN: We performed 24 h serum GH profiles
using 20 minute sampling and measured corresponding fasting concentrations of IGF
1 and IGFBP3. PATIENTS: Fourteen adult male long-term survivors of childhood
brain tumours were studied. All had received high dose cranial irradiation (> or
= 30Gy; median 12.8 (range 5.8-14.5) years previously). Nine healthy male
volunteers acted as controls. MEASUREMENTS: IGF-1 and IGFBP3 concentrations were
measured at 06.00 hours. Peak and trough GH activity within the GH profile was
analysed by a distribution method which determined the concentration at or below
which the serum GH concentration in the profile spent 95% (peak) and 5% (trough)
of the total time. RESULTS: Serum IGF-1 levels were significantly lower in the
irradiated group (Irradiated: 200 micrograms/l vs CONTROL: 265 micrograms/l; P =
0.001) but the difference in serum IGFBP3 (Irradiated: 2.3 mg/l vs CONTROLs: 2.77
mg/l; P = 0.03) was less marked. Peak GH activity was lower in the Irradiated
subjects (2.59 mU/l vs 9.04 mU/l; P = 0.0004) and correlated strongly with IGF-1
(r = 0.62; P = 0.002) but less so with IGFBP3 (r = 0.35; P = 0.09). This was
strenghtened when the range of activity within the profle (peak-trough) was
considered. Trough GH activity had a nonsignificant negative correlation with IGF
1 and IGFBP3 levels. CONCLUSION: The difference in serum IGF-1 concentrations
between irradiated subjects and controls was greater than the difference in serum
IGFBP3. Peak GH activity and the range of activity within the profile correlated
strongly with IGF-1 concentrations but less so with IGFBP3.
PMID- 10197081
TI - Outpatient assessment of residual growth hormone secretion in treated acromegaly
with overnight urinary growth hormone excretion, random serum growth hormone and
insulin like growth factor-1.
AB - OBJECTIVE: To assess the outpatient investigations, overnight urinary growth
hormone (uGH) excretion, random serum GH and insulin like growth factor 1 (IGF
1), and GH indices from the oral glucose tolerance test (OGTT) (fasting, nadir
and mean GH), as measures of mean GH secretion in treated acromegaly, in
comparison with a GH day series, which served as a gold standard. DESIGN:
Prospective cross-sectional study, with patients admitted to a metabolic ward for
the following investigations: random GH, IGF-1, 6 point GH day series (day 1), 9
h timed overnight uGH excretion, OGTT with GH response (day 2). Agreements
between the mean GH during the day series and the other outcome measures, and the
diagnostic performance of the latter, for the presence or absence of active
acromegaly (mean GH during day series > or = 5 or < 5 mU/l, respectively) were
determined. PATIENTS: 26 patients with treated acromegaly (11 with inactive
acromegaly off drug therapy). MEASUREMENTS: Serum GH and uGH were measured by
immunoradiometric assays and IGF-1 by radioimmunoassay. RESULTS: Agreements with
the mean GH during the day series were perfect for the nadir GH during the OGTT
with a 2 mU/l cutoff (Cohen's kappa (kappa) = 1, P < 0.00001), almost perfect for
the fasting and mean GH throughout the OGTT (both kappa = 0.92, P < 0.0001) and
random GH (kappa = 0.85, P < 0.0001), and substantial for the nadir GH with a 5
mU/l cutoff (kappa = 0.77, P < 0.0001), IGF-1 (kappa = 0.62, P < 0.001) and
overnight uGH excretion (kappa = 0.61, P = 0.002). Nadir GH with a 2 mU/l cutoff
was completely accurate for diagnosing the presence or absence of active
acromegaly (positive and negative predictive values (% +/- standard error
percentage) 100 +/- 8% and 100 +/- 10%). None of the outpatient tests used alone
was an adequate diagnostic test (positive and negative predictive values:
overnight uGH excretion -86 +/- 10% and 75 +/- 13%; random GH -100 +/- 11% and 85
+/- 11%; IGF-1 -92 +/- 10% and 71 +/- 13%) and so combinations of tests were
assessed. The best was overnight uGH excretion plus random GH (positive and
negative predictive values 88 +/- 9% and 100 +/- 12%). Using all three outpatient
investigations, the positive predictive value of three raised results was 100 +/-
13%. CONCLUSIONS: In treated acromegaly, residual GH secretion can be reliably
assessed with the OGTT, using standard diagnostic criteria. It can also be
assessed on an outpatient basis with overnight uGH excretion and random GH, as
direct measures, and IGF-1. If these are all normal, active acromegaly is
excluded. Three raised results denote active acromegaly, and one or two raised
results would need further investigation with a GH day series.
PMID- 10197082
TI - The outcome of surgery for acromegaly: the need for a specialist pituitary
surgeon for all types of growth hormone (GH) secreting adenoma.
AB - OBJECTIVE: Acromegaly is associated with reduced life expectancy, while
therapeutic 'cure' (defined by achievement of GH levels < 5 mU/l) is associated
with normalization of life expectancy. Surgery remains the treatment of choice
but in those in whom operative 'cure' is not achieved, radiotherapy and/or
medical treatment are valuable treatment modalities. The chance of subsequent
'cure' with radiotherapy or somatostatin analogue therapy is increased if the
post-operative GH level is reduced below 30 mU/l. Using strict criteria for cure
and a single dedicated pituitary surgeon, two large European studies reported
'cure' rates of 42% and 56%. In the Manchester region, surgery for these patients
has been performed by a number of neurosurgeons, with no specific designated
pituitary surgeon dominating the picture. We wished to examine the impact of this
surgical strategy on cure rates and the incidence of a post-operative GH level
below 30 mU/l. DESIGN: We reviewed the GH results between 1974 and 1997 for every
acromegalic who had been referred to the endocrine departments of the two
Manchester hospitals responsible for the majority of pituitary disease referrals
in Manchester and who had been subsequently referred for pituitary surgery.
PATIENTS AND MEASUREMENTS: Seventy-three (33 male) patients had had GH status
assessed before and after surgery by an OGTT or GH profile. The patients were
aged between 19 and 70 (mean 43) years at surgery. Seventy-one underwent
transsphenoidal and 2 transfrontal surgery. Nine surgeons performed operations.
RESULTS: Eighteen (24.7%) had microadenomas and 51 (69.9%) macroadenomas. In 4
patients (5.5%) insufficient data were available to size the adenoma. 17.8% of
patients were cured by surgery, 38.8% with microadenomas and 11.8% with
macroadenomas. In addition, of 52 patients whose GH levels were > 30 mU/l before
surgery, only 27 (51.9%) had GH levels below 30 mU/l post-operatively (81.8% of
microadenomas, 43.2% of macroadenomas). CONCLUSION: In comparison with other
series, the cure rate in this study is significantly lower. The success in
reducing GH levels below 30 mU/l post-operatively is difficult to compare with
previously published studies, as few groups have analysed their data in this
manner. Nonetheless, of our acromegalic patients with a pretreatment GH level in
excess of 30 mU/l, nearly 50% have similar GH status postoperatively, thereby
rendering them less amenable to cure by alternative therapeutic modalities. This
highlights the importance of a specialist pituitary surgeon, not only for GH
secreting microadenomas but also for GH secreting macroadenomas. If these
patients are not 'cured', the cost of continuing therapy becomes a significant
burden on health-care costs. In addition, if the postoperative GH levels remain
above 30 mU/l the chances of achieving adequate control of GH levels are greatly
reduced, thereby increasing mortality rates as well as morbidity in these
patients.
PMID- 10197083
TI - The effect of body composition on hexarelin-induced growth hormone release in
normal elderly subjects.
AB - OBJECTIVE: Growth hormone (GH) release is influenced by several factors including
age, gender, physical exercise, nutritional status, sex steroids and body
composition. The relationship with body composition is complex. Obesity is
accompanied by suppression of spontaneous and stimulated GH release. As
increasing body fat reduces stimulated GH secretion following a standard
provocative test, the potential clinical uses of GH-releasing peptides (GHRPs),
therapeutically or diagnostically, may be dependent on the relationship between
body fat and GHRP-stimulated GH release. We have therefore assessed the effect of
body composition and gender on the GH releasing capacity of hexarelin. DESIGN: A
single bolus of subcutaneous hexarelin at a dose of 1.5 micrograms per kg of body
weight was administered at time 0. Blood samples were taken at -10, 0, 10, 20,
30, 40, 50, 60, 90, 120, 170 and 180 min. SUBJECTS: Twenty-one (eight male)
healthy elderly subjects with a median (range) age of 68 (60-81) years and BMI of
26 (19-30) kg/m2 were studied. METHODS: Dual-energy X-ray absorptiometry (DEXA)
was used to assess body composition. RESULTS: Peak GH response correlated
negatively with fat mass, BMI, percentage body fat, and weight [r = -0.72, P =
0.0001; r = -0.56, P = 0.009; r = -0.63, P = 0.002 and r = -0.48, P = 0.029,
respectively,]. AUC GH correlated negatively with fat mass, BMI and percentage
fat mass [r = -0.58, P = 0.006; r = -0.51, P = 0.019 and r = -0.66, P = 0.001
respectively]. Using multiple linear regression, fat mass was the most useful
predictor for both peak GH response [R2 = 0.61, P < 0.0001] and AUC GH [R2 =
0.38, P = 0.003]. Gender was not a significant variable. CONCLUSIONS: Increasing
total fat mass results in a blunted GH response following subcutaneous hexarelin.
Total fat mass appears to be a useful predictor of peak GH response even in
normal individuals as none of the subjects in the present study was morbidly
obese. This indicates that there is a continuum of effect of fat mass on
hexarelin-stimulated GH release. Any impact of gender on the GH response to
hexarelin is almost certainly indirect and mediated via differences in body
composition. This observation will have an impact on the potential diagnostic and
therapeutic uses of hexarelin and related GH secretagogues.
PMID- 10197085
TI - HDL-cholesterol reductions associated with adult growth hormone replacement.
AB - OBJECTIVE: To study the effects of human growth hormone (hGH) replacement on
serum lipids and lipoprotein (a) (Lp(a)) concentrations. DESIGN: A randomized
double blind placebo controlled trial for 6 months followed by an open trial
where all patients were treated with hGH for a further 6 months. Treatment was
with recombinant hGH given in a dose of 0.125U/kg/wk increasing to 0.25U/Kg/wk.
PATIENTS: Thirty two patients with growth hormone deficiency were recruited, but
two withdrew because of side effects. Of the thirty patients (age 35.1 +/- 11.8
year; mean +/- SD) completing the study 13 of were assigned to the placebo group
for six months and 17 to active treatment from the start. MEASUREMENTS: Fasting
serum samples were analysed for total cholesterol, High density lipoprotein (HDL)
cholesterol, HDL-subfractions, triglycerides, lipoprotein (a) (Lp(a)) and IGF-1.
LDL-cholesterol was calculated using the Friedewald formula. RESULTS: Compared to
placebo, 6 months treatment with hGH therapy resulted in increased IGF-1 (37.6 +/
4.1 vs. 14.0 +/- 2.2 nmol/l, P < 0.01), but there was no significant difference
in any of the lipid parameters measured between placebo and active treatment
groups at 6 months. hGH was associated with a decrease in HDL-cholesterol
concentration from baseline to 6 months (0.97 +/- 0.08 to 0.76 +/- 0.10 mmol/l P
< 0.01), especially within the HDL2 subfraction. This reduction was maintained at
12 months. There was no change in Lp(a) concentrations from 0 to 6 months
(placebo -26 (-340 to 82), median and range, active -4 (-586 to 212) mg/l). There
was no change in total cholesterol, LDL-cholesterol, triglycerides or proportion
of HDL subfractions. CONCLUSIONS: Treatment with hGH can reduce serum HDL
cholesterol concentrations. Further investigation of this is required.
PMID- 10197084
TI - Bone mineral density, bone metabolism and body composition of children with
chronic renal failure, with and without growth hormone treatment.
AB - OBJECTIVE: Osteopenia has been reported in adult patients with chronic renal
failure (CRF). Only a few studies have been performed in children. The objective
of this study was to evaluate bone mineral density (BMD), bone turnover, body
composition in children with CRF and to study the effect of GH on these
variables. DESIGN: Two groups were identified: patients with growth retardation
who received GH (GH-group) and patients most of whom were not growth retarded who
did not receive GH (no-GH-group). After an observation period of 6 months, the
patients in the GH-group started GH treatment. Patients were studied every 6
months during 18 months. PATIENTS: Thirty-six prepubertal patients (27 boys and 9
girls), mean age 7.9 years, with CRF participated in the study. The GH-group
consisted of 17 patients of whom 14 completed one year treatment. The no-GH-group
consisted of 19 patients, of whom 16 were followed for 6 months, 14 for 12 months
and 13 for 18 months. MEASUREMENTS: Lumbar spine BMD, total body BMD and body
composition were assessed by dual energy X-ray absorptiometry, compared to age
and sex-matched reference values of the same population and expressed as standard
deviation scores (SDS). BMD of appendicular bone was measured by quantitative
microdensitometry (QMD). Blood samples were obtained to assess bone metabolism
and growth factors. RESULTS: Baseline mean lumbar spine and total body BMD SDS of
all patients were not significantly different from normal. Mean lumbar spine and
total body BMD SDS did not change significantly in the GH-group during GH
treatment. The change of QMD at the midshaft during the first 6 months of GH
treatment was significantly smaller than during the observation period (P <
0.01). Height SDS and biochemical markers of both bone formation and bone
resorption increased significantly during GH treatment; 1,25-dihydroxyvitamin D
remained stable. Lean tissue mass increased (P < 0.001) and percentage body fat
decreased (P < 0.01) during GH treatment. BMD, the biochemical markers of bone
turnover which are independent of renal function, and body composition remained
stable in the no-GH-group. CONCLUSIONS: Mean lumbar spine and total body BMD of
children with chronic renal failure did not differ from healthy controls. The
lack of a GH-induced increase in 1,25-dihydroxyvitamin D levels, probably due to
treatment with alpha-calcidol, might be linked to the absence of a response in
BMD during GH treatment in children with chronic renal failure.
PMID- 10197086
TI - Beta 3-adrenoreceptor gene polymorphism and leptin. Lack of relationship in type
2 diabetic patients.
AB - INTRODUCTION: The beta 3-Adrenergic receptor (beta 3AR) and leptin are molecules
involved in the regulation of energy balance. Recently, a mutation in the beta
3AR gene (Trp64Arg) has been reported to be associated with features of insulin
resistance, weight gain and early onset of Type 2 Diabetes Mellitus. The aim of
this study was to determine the frequency and clinical characteristics of the
Trp64Arg mutation in the beta 3AR gene in Type 2 diabetic patients, its
relationship with leptin levels, and its role in microangiopathic complications.
SUBJECTS AND METHODS: 187 Type 2 diabetic patients and 100 unrelated non-diabetic
subjects were studied. There was no difference between the diabetic and
nondiabetic subjects in the frequency of the Trp64 and Arg64 alleles (92.5% vs.
92.3% and 7.5% vs. 7.7%, respectively). Type 2 diabetic patients were divided
into two groups according to the presence (n = 27) or absence of the mutation (n
= 160). RESULTS: Mutation of the beta 3AR gene was not associated with any
differences either in the clinical and metabolic parameters or microangiopathic
complications. Type 2 diabetic patients carrying the Arg64 allele tended to have
a lower diabetes duration, but this was not statistically significant. Plasma
leptin levels were not different according to the beta 3AR genotype. CONCLUSIONS:
The Trp64Arg mutation is not a major determinant of Type 2 diabetes and its
microangiopathic complications. Moreover, this mutation was not clinically
relevant in leptin regulation.
PMID- 10197087
TI - Carcinoid tumours presenting as breast cancer: the utility of radionuclide
imaging with 123I-MIBG and 111In-DTPA pentetreotide.
AB - Secondary tumours of any type in the breast are rare. A review of the literature
demonstrated only 23 cases of carcinoid tumours with associated breast
metastasis, as distinct from primary carcinoid tumours of the breast. Distant
metastases from carcinoid tumours are correlated with poor prognosis and
survival. Although both primary and metastatic mammary carcinoid tumours are
uncommon, the recognition of the true origin of the tumours may be of importance
owing to the different clinical management and prognosis of the two conditions.
Recently, radionuclide-labelled imaging techniques have been applied to the
localization of such lesions, based on isotope uptake by receptors present in
these neuroendocrine tumours. We report two new cases of carcinoid tumours with
breast metastases, the primaries being in the ileocaecal valve and the bronchus,
respectively. The diagnosis of a carcinoid tumour was based on the clinical,
biochemical, histopathological and immunostaining features. Furthermore, these
patients had both 123I-MIBG and 111In pentetreotide scintigraphy performed. These
radionuclides play a useful role in the localization and potentially in the
management of carcinoid tumours and their distant metastases.
PMID- 10197088
TI - Low dehydroepiandrosterone sulphate (DHEAS) levels in X-linked
adrenoleukodystrophy.
PMID- 10197089
TI - Repetition of data in publications on DNA flow cytometry in phaeochromocytoma.
PMID- 10197090
TI - Physician-assisted suicide: issues facing doctors.
PMID- 10197091
TI - Self-regulation: what is the future?
PMID- 10197092
TI - Radiology of the duodenum.
AB - Radiological imaging techniques play an important role in the diagnosis of
duodenal disorders. The radiological appearances of a variety of interesting but
uncommon disorders that involve the duodenum, particularly the duodenal loop, are
reviewed.
PMID- 10197093
TI - Novel treatments in inflammatory bowel disease.
AB - Recent advances in inflammatory bowel disease therapeutics have led to improved
formulations of existing treatments and new indications for established drugs.
Truly novel therapies based on recent understanding of pathogenesis are also
being developed. These new treatments and their likely impact on the management
of inflammatory bowel disease in the future are discussed.
PMID- 10197094
TI - Gastrointestinal manifestations of HIV infection.
AB - As patients with human immunodeficiency virus (HIV) infection become more
immunocompromised, gastrointestinal symptoms become more common. Most symptoms
result from opportunistic infections and can be diagnosed and treated by
gastroenterologists, although medical microbiology and histopathology input is
essential.
PMID- 10197095
TI - Cystic fibrosis presenting in adults.
AB - Cystic fibrosis is a common genetic disease occurring in children. Milder forms
of cystic fibrosis are increasingly being recognized as presenting in adults as
well. This article describes the various ways in which cystic fibrosis can
present in adult patients.
PMID- 10197096
TI - Image-guided neurosurgery.
AB - Accurate localization of lesions and minimization of trauma to the surrounding
brain are of paramount importance in intracranial surgery. Stereotactic frame
systems provide highly accurate methods of localization, which has been further
enhanced by the introduction of sophisticated imaging modalities, and recently by
the development of interactive image-guided neurosurgical technology.
PMID- 10197097
TI - Therapeutic trends in cutaneous melanoma.
AB - Many advances in the management of melanoma have occurred in the last few years.
These make this an exciting time for clinicians and allows them to offer glimmers
of hope for patients with this disease. This article looks at the therapeutic
aspects of the treatment of cutaneous melanoma.
PMID- 10197099
TI - The case for combination therapy in achieving blood pressure targets.
PMID- 10197098
TI - Improving the outcome of acute stroke management.
AB - Recent research into stroke mechanisms suggests that it may be possible to reduce
mortality and improve functional outcome in stroke patients, provided clinicians
act quickly and appropriately. In this article, standards for optimal stroke
management with new therapeutic strategies aiming to restore cerebral blood flow
and to protect brain neurons will be discussed.
PMID- 10197100
TI - Myositis and malignancy: is there a true association?
AB - There may be an association between polymyositis/dermatomyositis and malignant
disease. Cancer occurs in patients with polymyositis/dermatomyositis with a
frequency estimated between 2.5% and 29% (relative risk 1.0 to 6.5). We present
two such cases, associated with colorectal carcinoma and non-Hodgkin's lymphoma
respectively, together with an overview of existing controlled studies in the
area.
PMID- 10197101
TI - Modernizing medical education.
AB - Continuing medical education, continuing professional development and the
increasing importance of clinical governance all add to the challenge of
delivering life-long learning to the profession. Use of the Internet to deliver
this education provides a number of solutions and potential cost savings.
PMID- 10197102
TI - The experience of Spanish trainees in the UK (1986-1996): a tragedy in four acts.
AB - In 1986 Spain became a member of the European Economic Community. Since then an
increasing number of Spanish doctors have come to the UK seeking specialist
training. This article gives a brief account of their experience.
PMID- 10197103
TI - Coexistent renal and heart failure: the importance of recognizing 'congestive
cardio-renal failure'.
PMID- 10197104
TI - Splenic injury following routine colonoscopy.
PMID- 10197105
TI - Paracetamol as a cause of anaphylaxis.
PMID- 10197106
TI - Rapid opiate detoxification under anaesthesia.
PMID- 10197107
TI - Risk assessment and MRSA.
PMID- 10197108
TI - Fosphenytoin and status epilepticus.
PMID- 10197109
TI - Anaesthesia for Hurler's syndrome.
PMID- 10197110
TI - Development of echocardiography.
PMID- 10197111
TI - Anaesthesia for a patient with severe cardiorespiratory disease.
PMID- 10197112
TI - Calman proposals for cancer: where are they going?
PMID- 10197113
TI - Management of leg ulcers.
AB - Management of leg ulcers requires attention to a checklist of causes of delay in
healing, the commonest cause of which is venous disease. Arterial disease must be
excluded before fully effective management of venous disease is possible.
Lymphatic failure is also worthy of attention. 'Keep moving' is an important
management theme for the whole team, including the patient.
PMID- 10197114
TI - Pressure injuries: causes and prevention.
AB - Pressure injuries are caused by peripheral circulatory failure in acutely ill or
traumatized patients, which is exacerbated by increased tissue deformability over
bony prominences as a result of hypotension, dehydration or poor muscle tone.
PMID- 10197115
TI - Common causes of leg ulceration.
AB - Good treatment of any leg ulcer depends upon an accurate diagnosis of the
underlying cause. Most leg ulcers occur secondary to venous or arterial disease
but other rarer causes sometimes need to be considered. The treatment of the
underlying condition is far more important than the choice of dressing.
PMID- 10197116
TI - The prevalence of leg ulcers in hospitals.
PMID- 10197117
TI - Practical advice on treating haematemesis.
AB - This article covers the causes of haematemesis, discusses how to resuscitate the
patient and addresses the gastroenterologist's approach to commonly encountered
causes of haematemesis such as peptic ulcers and oesophageal varices.
PMID- 10197118
TI - Induction of labour: new horizons.
AB - Induction of labour may be indicated in the maternal or the fetal interest, and
is more likely to be successful if physiological mechanisms are replicated.
Induction of labour in the presence of an unfavourable cervix presents the
greatest challenge and pharmacological techniques must encourage cervical
ripening if we are to advance our management of this common obstetric
intervention.
PMID- 10197119
TI - Training and supervision in effective cross-cultural mental health services.
AB - For mental health professionals working in areas with large black and minority
ethnic populations, adequate training and continuing supervision are essential in
providing culturally acceptable services. Local multidisciplinary training is the
most suitable method of integrating training and supervision and developing
culturally appropriate services.
PMID- 10197120
TI - Cutaneous melanoma: diagnosis and at risk patients.
AB - Malignant melanoma is a condition which kills many young people, yet early
recognition can lead to cure. There are, however, new approaches to diagnosis and
management of disease at high risk of recurrence, which raise glimmers of hope in
this most capricious of conditions.
PMID- 10197121
TI - Environment and health.
AB - There is a clear connection between environment and health. This article outlines
the importance of the quality of the environment and the role of the public
health function in working across the NHS and local government to improve
population health.
PMID- 10197122
TI - Intermediate not indeterminate care.
AB - Increasing demands, limited resources and an aging population are driving the
development of alternatives to the full acute hospital bed. This review considers
some opportunities and pitfalls, and proposes some principles for practice.
PMID- 10197123
TI - Local anaesthetics: an overview of current drugs.
AB - Local anaesthetics are one of the most widely used classes of drugs in clinical
practice. When they are given systemically, cardiac, skeletal and smooth muscle
may be affected, as well as the peripheral and central nervous systems and the
specialized conducting system of the heart. Knowledge of the pharmacology,
action, metabolism and side-effects is vital for safe use of these drugs.
PMID- 10197124
TI - Don't take your eye off the ball.
AB - Improvement in the professional career development of junior doctors is dependent
on the promised expansion of the consultant grade. The government and its
advisors should concentrate on achieving this goal before all others.
PMID- 10197125
TI - Staff grades and associate specialists: their continuing professional development
and aspirations.
AB - A survey of staff grades and associate specialists in the Oxford deanery showed
that there were slightly more females (53%). There were 44% who had on-call
commitments, a third of these were first on call. Thirty-eight per cent of the
staff grades and 55% of the associate specialists had membership or fellowship of
their relevant Royal College. The majority undertake continuing professional
development and a majority would like promotion but only a small minority is
prepared to relocate to further their training.
PMID- 10197126
TI - A dissection with a difference: an unusual case of ascending aortic dissection
secondary to granulomatous aortitis.
PMID- 10197127
TI - Elastofibroma dorsi: a rare tumour.
PMID- 10197128
TI - An unusual cause of headache.
PMID- 10197129
TI - Diagnosis of back pain.
PMID- 10197130
TI - Airway control in severe facial injury.
PMID- 10197131
TI - Seriously ill for medical research.
PMID- 10197132
TI - Violence against women.
PMID- 10197133
TI - Violence against women.
PMID- 10197134
TI - The importance of income protection for doctors.
PMID- 10197135
TI - Dilatation and curettage in a morbidly obese woman.
PMID- 10197136
TI - The molecular pathology of tumours of the ear and temporal bone.
PMID- 10197137
TI - The prevalence of allergic rhinosinusitis: a review.
AB - A review of the literature indicates that there is an increase in the prevalence
of self-reported symptoms suggestive of seasonal allergic rhinitis over the last
70 years. The reason for this remains unclear. Epidemiological studies which
relate to the effect of pollution suggest that while pollution can exacerbate
respiratory tract symptoms, there is no consistent evidence that high levels
result in an increase in the prevalence of allergic rhinitis. The increased
prevalence of house-dust mite, an alteration in immunity--possibly related to the
number of childhood respiratory tract infections, and increased disease
awareness, are all factors which may influence the reported prevalence of
allergic rhinitis. At present the inconsistencies which exist in the literature
mean that it is possible to 'pick' publications which support one view and ignore
the rest, so that a variety of views may be held, each with apparently well
referenced endorsement. The criteria defined by Bradford Hill (1965) to establish
causation and not mere association between any of these factors and allergic
rhinitis have, as yet, not been met (see Table V).
PMID- 10197138
TI - Selective lateral neck dissection for laryngeal cancer with limited metastatic
disease: is it indicated?
AB - The most important prognostic factor in cancer of the larynx is the presence of
cervical metastatic disease, which is the most common type of recurrence in such
patients. Because micrometastases cannot be detected pre-operatively at present,
selective lateral neck dissection is increasingly recommended as the standard
treatment for patients with a clinically negative neck in order to reduce the
recurrence rate. In cases of N+ disease, selective lateral neck dissection can be
as valid as modified radical neck dissection, providing patients have only
limited, occult metastatic disease.
PMID- 10197140
TI - Study of ethmoid sinus involvement in multibacillary leprosy.
AB - The nasal mucosal involvement in lepromatous leprosy is well recognized.
Currently interest has centred around the involvement of paranasal sinuses in
leprosy. They act as a reservoir and constant source of reinfection to the nasal
mucosa. In the present prospective study 25 untreated patients with multi
bacillary leprosy were included. Clinical examination, computed tomography (CT)
scan of paranasal sinuses, ethmoid sinus endoscopy and biopsy were carried out in
all patients, to investigate the involvement of the paranasal sinuses in leprosy.
Ethmoid sinus involvement was noted in 20 patients on CT scan. Bilateral
involvement was more common (65 per cent). Anterior ethmoids were more commonly
affected (65 per cent). On ethmoid sinus endoscopy abnormal mucosa was noted in
17 patients (68 per cent). Ethmoid sinus biopsy was confirmative in 16 patients
(64 per cent). Statistically significant correlation was found between CT
findings, sinus endoscopy and sinus biopsy findings.
PMID- 10197139
TI - Changes in the clinical presentation of chronic otitis media from the 1970s to
the 1990s.
AB - Clinical features of 1123 patients with chronic otitis media referred to a
Finnish university hospital for surgical treatment over a 20-year period were
analyzed. The number of patients declined by 48 per cent from the period 1976
1985 to 1986-1995. The decline was evident in all age groups but the proportion
of children increased significantly from 14 per cent in 1976-1985 to 20 per cent
in 1986-1995. A male predominance was noted with the exception of patients with
sequelae of otitis in whom the sex distribution was equal. In cholesteatomatous
ears, no significant change occurred in the type or size of cholesteatomas or in
the incidence of ossicular destruction. Likewise, no significant change was noted
in the size of perforations or in the incidence of ossicular destruction in
patients with dry eardrum perforations. However, hearing levels of patients
treated 1976-1985 were significantly worse than those of patients 1986-1995.
Severe complications caused by the disease were rare during both periods.
PMID- 10197141
TI - The effect of cetirizine on symptoms and signs of nasal polyposis.
AB - Forty-five patients with residual or recurrent nasal polyposis after
ethmoidectomy were treated with either cetirizine at twice the daily recommended
(20 mg) dose or placebo for three months. The number and size of polyps remained
unchanged during the study period. Cetirizine was found to reduce nasal sneezing
and rhinorrhoea effectively. The drug also had a beneficial effect on nasal
obstruction in the latter part of the study. The side effects of 20 mg (double
the recommended daily adult dose) of cetirizine were few and comparable to
placebo.
PMID- 10197142
TI - Admission and discharge policy for paediatric adenoidectomy and tonsillectomy--a
rural perspective.
AB - Adenoidectomy and tonsillectomy are amongst the most common surgical procedures
carried out in children. We undertook a prospective audit in the Highlands of
Scotland to document the views of general practitioners, parents, nursing staff
and anaesthetists on admission and discharge policy. Of responses from 149
general practitioners, 119 (80 per cent) were in favour of change to same day
admission and 22 (15 per cent) were not in favour. For change to same day
discharge for adenoidectomy, 55 (37 per cent) were in favour and 81 (54 per cent)
were not in favour. For change to next day discharge for tonsillectomy, the
figures were 51 (34 per cent) and 89 (60 per cent) respectively. Responses from
14 trained paediatric nurses comprised 13 not in favour of same day admission,
six in favour and seven not in favour of same day discharge for adenoidectomy and
all 14 not in favour of same day discharge for tonsillectomy. All eight
Consultant anaesthetists approached were happy with a change in policy to same
day admission for children who were otherwise fit and well. Thirty-seven parents
(70 per cent) preferred previous day admission and 14 (29 per cent) were happy
with same day admission for their children. On the basis of these results, day
case adenoidectomy or tonsillectomy is not being considered in this area. Moves
have been made, however, toward a policy of same day admission and next day
discharge.
PMID- 10197143
TI - A skull base extradural hypoglossal neurilemmoma resected via an extended
posterolateral approach.
AB - The case of a 43-year-old man with a right skull base hypoglossal neurilemmoma
excised via the extended posterolateral approach is presented. There is only one
previous case of hypoglossal neurilemmoma in the literature. The surgical
technique described is a new approach to the posterior skull base involving a
suboccipital craniectomy, mastoidectomy and the removal of the lateral process of
the atlas. It provides an inferior approach to the jugular foramen and
hypoglossal canal that allows the lower cranial nerves to be identified as they
exit from their skull base foramina. In the discussion we compare this technique
to other surgical approaches previously described for access to the region of the
jugular foramen.
PMID- 10197144
TI - Hypoparathyroidism after the treatment of laryngopharyngeal carcinoma.
AB - Thirty patients with squamous cell carcinoma of the laryngopharynx were treated
with surgery (total laryngectomy and hemithyroidectomy) and radiotherapy. Group 1
(n = 7) patients had surgery only; Group 2 (n = 7) had radiotherapy followed by
salvage surgery while Group 3 (n = 16) had surgery followed by radiotherapy.
Parathyroid hormone and calcium levels were measured pre- and post-operatively
and post-radiotherapy. In Group 1 no patients were hypoparathyroid. In Group 2,
29 per cent of patients preoperatively and 57 per cent post-operatively, were
hypoparathyroid. In Group 3, no patients were hypoparathyroid pre-operatively,
while 25 per cent were hypoparathyroid post-operatively and post-radiotherapy.
Parathyroid hormone and calcium levels were averaged and compared within and
between each group. There was no significant difference within each group, when
comparing levels post-operatively and post-radiotherapy from those of pre
operatively. There was no significant difference in levels between each of Groups
1, 2 or 3 (p > 0.05).
PMID- 10197145
TI - A clinic for the rapid processing of patients with neck masses.
AB - Neck masses are common and may have serious underlying pathology. There is much
anxiety and confusion in primary care as to which hospital department will
provide the patient with the best service and the swiftest diagnosis. A clinic
was set up at Wexham Park hospital to enable patients with neck masses to be seen
early, and to undergo a one-stop specialist evaluation, ultrasound scan and fine
needle aspiration biopsy. The clinic has yielded a wide variety of benign and
malignant pathology. The first 100 patients are discussed and evaluated.
PMID- 10197146
TI - The Scheibe cochlea deformity with macrocephaly: a case for single channel
implantation.
AB - An 11-year-old congenitally deaf child with bilateral primitive common cavity
(Scheibe type) cochleosaccular dysplasia and benign familial macrocephaly was
implanted with an extracochlear single channel device with an ear level speech
processor. This paper describes the assessment, findings, dilemmas in decision
making, surgical procedure and the favourable outcome after implanting. The
relevant literature has been reviewed and our case is presented for the unusual
combination of features.
PMID- 10197147
TI - Brainstem pathology of infantile Gaucher's disease with only wave I and II of
auditory brainstem response.
AB - We studied the auditory brainstem response (ABR) and neuropathology in a female
infant who died at six months of age because of typical infantile Gaucher's
disease. The patient was hospitalized for hepatosplenomegaly and failure to
thrive. Her ABR showed only waves I and II. The neuropathological study disclosed
that: (1) Gaucher's cells were found in the perivascular region of the cerebrum
and anterior ventral nucleus of the thalamus. (2) Gliosis was found in the dorsal
part of the brainstem rather than the ventral part. (3) Neuronal cells in the
superior olivary nucleus were lost, and marked gliosis was found in the cochlear
nucleus. The disappearance of wave III and later waves of ABR could be supported
by these pathological findings.
PMID- 10197148
TI - Late complications of nasal augmentation using silicone implants.
AB - Alloplastic nasal augmentation with silicone elastomer (Silastic) is popular in
areas of Asia. Although the silicones are bio-inert, they have been implicated in
a number of adverse reactions after implantation. We report our experience of
three patients who presented with late complications after nasal augmentation
using Silastic implants. The mechanisms of implant failure are proposed. It is
advised that this material should only be used on an individual basis in
carefully selected cases.
PMID- 10197149
TI - Metastatic testicular teratoma of the nasal cavity: a rare cause of severe
intractable epistaxis.
AB - Malignant neoplasms of the nasal cavity and paranasal sinuses are uncommon.
Choriocarcinoma is a highly malignant germ cell tumour occurring in the
reproductive organs. Metastasis may be principally by the lymphatic route as in
other germ cell tumours but choriocarcinoma is also known to spread
haematogenously. We present a rare case of metastatic choriocarcinoma to the
nasal cavity from testicular teratoma presenting with intractable epistaxis in a
32-year-old Caucasian male, who ultimately succumbed to this disease.
PMID- 10197150
TI - Recovery of function after intracordal autologous fat injection for unilateral
recurrent laryngeal nerve paralysis.
AB - The present report documents the successful outcome in three patients with a
unilateral recurrent laryngeal nerve paralysis managed with an intracordal
injection of autologous fat who ultimately experienced a complete recovery of
function. Such data demonstrates the safety of intracordal autologous fat
injection in patients who ultimately recover function.
PMID- 10197151
TI - Pharyngeal pouch following anterior cervical fusion.
AB - A case of an acquired pharyngeal pouch which formed as a consequence of previous
anterior cervical fusion is reported. This is a rare cause of pharyngeal pouch
formation with only one such case previously reported in the English language
literature. In our case adhesions had formed between the posterior pharyngeal
wall and the area around the screw used to hold the Senegas plate on the anterior
aspect of the fifth to seventh cervical spinal vertebrae.
PMID- 10197152
TI - An unusual complication of Cloward's procedure presenting to the
otolaryngologist.
AB - We present the case of a 51-year-old lady who developed a CSF leak following a
Cloward's procedure (anterior cervical surgery with fusion), which settled with
conservative management. Two months following the surgery she was assessed by an
otolaryngologist for persistent dysphagia and a swelling in the anterior triangle
of her neck. A computed tomography (CT) scan identified a fluid-filled mass
displacing the trachea and communicating with the anterior cervical vertebrae,
thus confirming the persistence of a CSF leak.
PMID- 10197153
TI - Dysphagia secondary to invasive candidiasis of a jejunal free flap.
AB - The presence of a mass in a jejunal free flap that causes dysphagia less than two
years after a pharyngolaryngectomy for carcinoma usually indicates tumour
recurrence. We present a case of invasive candidiasis of a jejunal free flap
presenting with dysphagia and a mass. To our knowledge this is previously
unreported. Such a cause should always be considered in the differential
diagnosis, as early recognition and treatment are likely to result in a
favourable outcome.
PMID- 10197154
TI - Mucocele mimicking a Warthin's tumour recurrence.
AB - We report an unusual case of an extravasation mucocele complicating superficial
parotidectomy. The tumour excised was a Warthin's tumour. Three months following
the primary surgery a cystic lesion appeared in the parotid bed. It was initially
thought to represent a recurrence. The area was re-explored and a mucocele
excised. The pathogenesis of mucoceles and the difficulties encountered when
dealing with parotid tumour recurrence are discussed.
PMID- 10197155
TI - Pseudoaneurysm of subclavian artery--atypical presentation.
AB - We present a rare case of pseudoaneurysm of right subclavian artery who presented
with supraclavicular mass. Injury of the subclavian artery causing pseudoaneurysm
is a serious surgical emergency and a surgical intervention is indicated.
PMID- 10197156
TI - Intra-operative ultrasound-guided drainage of parotid abscess.
AB - Parotitis complicated by parotid abscess remains a potentially life-threatening
problem. Conventional surgical treatment involves incising the parotid parenchyma
in the direction of the facial nerve until the abscess is located and evacuated.
Intra-operative ultrasound greatly assists in localizing the abscess and in
ensuring its complete drainage. Expeditious and exact localization of the abscess
reduces operative time. Equally importantly, ultrasound-assisted drainage reduces
surgical dissection and the potential for facial nerve damage.
PMID- 10197157
TI - An aggressive and invasive growth of juvenile papillomas involving the total
respiratory tract.
AB - A malignant course of juvenile laryngeal papillomatosis has rarely been reported.
In the present case the patient had had laryngeal papillomas since the age of
three years. The papillomas gradually spread to the entire respiratory system,
and during 30 years the patient was operated on more than 80 times. At present an
invasive tumour spreading from the tongue into the parapharyngeal space,
extending to the cranial base, has been demonstrated by magnetic resonance
imaging (MRI). Intralesional therapy with Cidofovir, a promising antiviral drug
against human papillomavirus (HPV) infection, was started with some clinical
effect, although only on the superficial tumour growth. Histology of removed
tumour tissue has demonstrated a mixture of exophytic and inverted growth
pattern, and has mainly been interpreted as benign, in spite of a focally high
mitotic index and an intermittent lack of maturation in the epithelium. In the
most recent biopsies a verrucous carcinoma has been diagnosed. Expression of p53
was noted to increase in papillomas with time. All samples have been shown to
harbour HPV 11, but no other HPV types.
PMID- 10197158
TI - Environmental influences on epilepsy gene mapping in EL mice.
AB - The epileptic EL mouse has been studied extensively as a genetic model for
idiopathic complex partial seizures in humans. The seizures in EL mice occur
during routine handling at approximately 90 days of age, but can be induced at
younger ages (50 days) by repeated rhythmic vestibular stimulation, e.g.,
tossing. Six seizure frequency quantitative trait loci (QTLs), El1-El6, were
previously mapped in crosses between EL and non-epileptic strains using
mechanical tossing procedures beginning at 30 days of age. The presence of these
seizure frequency QTLs depended upon genetic background and the type of cross.
Here we confirm Chromosome 2 and 9 QTLs in a backcross to the seizure-resistant
ABP/LeJ strain with mice tested beginning at 200 days of age. However, the
mapping of epilepsy genes was influenced by the seizure testing procedure, i.e.,
repeated tossing. The maximum Z-score for El1 (Chromosome 9) was 3.7 after 6
tests, but decreased to 2.4 after 15 tests. In contrast, the maximum Z-score for
El2 (Chromosome 2) was 2.0 after 6 tests, but increased to 3.9 after 15 tests. In
addition to nonallelic interactions (epistasis), our findings indicate that the
genetic complexity of tossing-induced seizure susceptibility in EL mice also
arises from genotype-environmental interactions involving the seizure test,
seizure history, and age.
PMID- 10197159
TI - The vestigial gene of Drosophila melanogaster is involved in the formation of the
peripheral nervous system: genetic interactions with the scute gene.
AB - The vestigial (vg) gene of Drosophila melanogaster encodes a novel nuclear
protein which is required for wing formation but its function is not restricted
to this developmental process. In this report, we have examined the possible role
of vestigial in the formation of the peripheral nervous system. We found that
most vestigial mutants display ectopic or missing macrochaetae. We also show that
vestigial interacts in a dose dependant manner with different alleles of the
scute gene and with the extramacrochaetae gene and that mis-expression of the
vestigial gene in the wing disc increases the domain of scute expression and
allows the formation of supernumerary ectopic bristles. From these results, we
conclude that vestigial affects scute expression and plays a role in the
differentiation of the peripheral nervous system.
PMID- 10197160
TI - Dopamine modulates female sexual receptivity in Drosophila melanogaster.
AB - Newly eclosed Drosophila melanogaster flies were systemically depleted of
dopamine by feeding an inhibitor of the biosynthetic enzyme, tyrosine
hydroxylase, and analyzed for abnormalities in courtship behavior. Dopamine
depleted females were significantly less receptive to males than were control
females, although males were strongly attracted to treated females. The decrease
in receptivity was reversed by the addition of L-DOPA (the product of the
tyrosine hydroxylation reaction) to food containing the inhibitor. Male courtship
behaviors were unaffected by this treatment. Female receptivity may be regulated
via interactions with hormonal pathways, since depletion of dopamine levels via
inhibition of tyrosine hydroxylase activity in Drosophila melanogaster adult
females has established that dopamine is required for normal ovarian maturation
and fecundity.
PMID- 10197161
TI - Memory states and memory tasks: an integrative framework for eyewitness memory
and suggestibility.
AB - An integrative framework (IMP) is presented which depicts performance in
eyewitness suggestibility experiments as the participants' solutions of memory
tasks, depending on (a) a specified task-relevant memory base and (b) the
participants' perception of the memory task. Three theoretical explanations of
the effect of misleading post-event information are reinterpreted and reduced to
one single core: individuals answer test questions while assuming the consistency
of event and post-event information. The impact of such consistency assumptions
(a) is demonstrated in a first experiment, where the usual misinformation effect
obtained with the Loftus standard test procedure disappeared when the
participants' consistency assumptions were destroyed prior to testing, and (b)
manifests itself in a qualitative analysis of individual processing strategies
for discrepancies between details. Experiment 2, employing methodological
innovations suggested by IMP, examined the memory base and found no evidence for
memory impairment or misattributions of post-event details to the witnessed
scene. However, a follow-up study conducted four and a half months later revealed
a strong tendency for such misattributions which might indicate long-term
integration of information.
PMID- 10197162
TI - Successive tests of pair recognition.
AB - A large number of experiments have found a moderate degree of dependence between
subsequent tests of recognition and cued recall as described by the TW-function.
This paper investigates the dependence in word pair recognition. Tests of word
pair recognition are conducted with the subsequent test being free recall, cued
recall, recognition, and cued recognition. The dependence is compared to
subsequent tests of cued recognition (i.e. recognition of a target with the
presence of a cue). The results are related to a general theory of memory called
TECO (Target, Event, Cue, & Object, see Sikstrom 1996b). This theory makes
different quantitative predictions depending on the number of shared connections
in the subsequent tests. Using a function suggested by TECO, different degrees of
dependencies are predicted for pair and cued recognition. The predictions of the
TECO-function show a non-significant deviation from observed data, whereas those
of the TW-function deviate significantly in all conditions.
PMID- 10197163
TI - Strategies for generating multiple instances of common and ad hoc categories.
AB - In a free-emission procedure participants were asked to generate instances of a
given category and to report, retrospectively, the strategies that they were
aware of using in retrieving instances. In two studies reported here,
participants generated instances for common categories (e.g. fruit) and for ad
hoc categories (e.g., things people keep in their pockets) for 90 seconds and for
each category described how they had proceeded in doing so. Analysis of the
protocols identified three broad classes of strategy: (1) experiential, where
memories of specific or generic personal experiences involving interactions with
the category instances acted as cues; (2) semantic, where a consideration of
abstract conceptual characteristics of a category were employed to retrieve
category exemplars; (3) unmediated, where instances were effortlessly retrieved
without mediating cognitions of which subjects were aware. Experiential
strategies outnumbered semantic strategies (on average 4 to 1) not only for ad
hoc categories but also for common categories. This pattern was noticeably
reversed for ad hoc categories that subjects were unlikely to have experienced
personally (e.g. things sold on the black market in Russia). Whereas more
traditional accounts of semantic memory have favoured decontextualised abstract
representations of category knowledge, to the extent that mode of access informs
us of knowledge structures, our data suggest that category knowledge is
significantly grounded in terms of everyday contexts where category instances are
encountered.
PMID- 10197164
TI - Expression of NG2/human melanoma proteoglycan in human adult articular
chondrocytes.
AB - OBJECTIVE: NG2 is a transmembrane chondroitin sulfate (CS) rich proteoglycan
originally identified in rats. It has recently been shown to be identical to
human melanoma proteoglycan (HMPG). In rats NG2 has a limited distribution in
adult tissues, being expressed predominantly by neuronal and glial cells whereas
during development it is also expressed in developing mesenchyme including
cartilage. NG2/HMPG has putative roles in interactions between glial and melanoma
cells with extracellular matrix (ECM) molecules. This study was undertaken to
assess whether NG2/HMPG was expressed by normal and osteoarthritic human
articular chondrocytes. DESIGN: Cryostat sections of human fetal knee joints and
normal and osteoarthritic articular cartilage were immunostained with antibodies
against rat NG2 (N143.8) and HMPG (M28B5, 9.2.27). Immunoprecipitation and
Western blotting was carried out on protein extracts of chondrocytes from normal
and osteoarthritic cartilage. Immunofluorescence of NG2 and potential ligands was
carried out in vitro on cells from normal and osteoarthritic cartilage. RESULTS:
Fetal and both normal and osteoarthritic adult cartilage showed strong
immunoreactivity for NG2/HMPG. Western blotting showed a smeared component of
molecular weight greater than 400 kDa and a faint band at 250 kDa which became
predominant upon digestion with chondroitinase ABC. Immunofluorescence of
chondrocytes in vitro showed NG2 to be distributed in a punctate pattern without
co-localization of actin or several ECM proteins including fibronectin and type
VI collagen. CONCLUSION: NG2/HMPG is expressed by human fetal and adult
chondrocytes and in adult articular chondrocytes the core protein is chondroitin
sulfated. The function of this molecular in human articular cartilage remains to
be defined.
PMID- 10197165
TI - Differential effects of local application of BMP-2 or TGF-beta 1 on both
articular cartilage composition and osteophyte formation.
AB - OBJECTIVE: The related molecules bone morphogenetic protein-2 (BMP-2) and
transforming growth factor beta-1 (TGF-beta 1) have both been shown to stimulate
chondrocyte proteoglycan (PG) synthesis in vitro. We investigated the in-vivo
effects of these factors on articular cartilage PG metabolism. DESIGN: Several
doses of BMP-2 or TGF-beta 1 were injected into the murine knee joint, once or
repeatedly. Patellar cartilage PG synthesis was measured by [35S]-sulfate
incorporation and reverse transcriptase polymerase chain reaction (RT-PCR). PG
content was analyzed by measuring safranin O staining intensity on histologic
sections. RESULTS: A single injection of 200 ng BMP-2 induced a much earlier and
more impressive stimulation of articular cartilage PG synthesis, than 200 ng TGF
beta 1. RT-PCR revealed that both factors upregulated mRNA of aggrecan more than
that of biglycan and decorin. However, 21 days after a single injection of 200 ng
TGF-beta 1 PG synthesis still was significantly increased, while stimulation by
BMP-2 only lasted for 3 to 4 days. Stimulation by BMP-2 could be prolonged to at
least 2 weeks by triple injections of 200 ng each, at alternate days. Remarkably,
even after this intense exposure to BMP-2, stimulation of PG synthesis was not
reflected in long-lasting enhancement of PG content of articular cartilage. In
contrast, even a single injection with 200 ng of TGF-beta 1 induced prolonged
enhancement of PG content. After repeated injections, both BMP-2 and TGF-beta 1
induced chondrogenesis at specific sites. 'Chondrophytes' induced by BMP-2 were
found predominantly in the region where the growth plates meet the joint space,
while those triggered by TGF-beta 1 originated from the periosteum also at sites
remote from the growth plates. CONCLUSIONS: BMP-2 and TGF-beta stimulate PG
synthesis and PG content with different kinetics, and these factors have
different chondro-inductive properties.
PMID- 10197166
TI - Where does it hurt? Pain localization in osteoarthritis of the knee.
AB - OBJECTIVE: To identify the most common sites of pain in symptomatic knee
osteoarthritis (OA) and to investigate clinical, radiographic and psychosocial
associations of pain occurring in different locations. DESIGN: Sixty-eight
outpatients with knee OA were interviewed in detail about their knee pain.
Location of pain was recorded on a standard drawing of the knee. Validated
instruments were used to measure pain severity, function, depression, anxiety,
quality of life, fatigue, helplessness, self efficacy. Pain threshold was
measured by dolorimetry and a knee examination performed. Radiographs
(anterioposterior and lateral) were viewed if available. RESULTS: Most (85.3%)
patients reported either 'generalized' (N = 35, 51.5%) or 'medial' (N = 23,
33.8%) knee pain. There were no differences between groups in pain severity,
demographic or psychosocial variables, pain threshold or radiographic location or
severity. However, function was significantly worse in the 'generalized' group
(WOMAC function score 48.9 +/- 20.8 vs 34.2 +/- 22.3; P = 0.01): this remained
significant after adjustment for potential confounding factors. The difference in
function was most marked for activities involving knee bending. Early morning
stiffness was also greater in the generalized group. CONCLUSIONS: Knee pain is
not the same in all individuals with knee OA, confirming the heterogeneity of the
condition. Location of pain is usually either generalized or medial. Patients
with these patterns do not differ in demographic, radiographic or psychosocial
variables but important differences in functional ability can be detected,
suggesting differences in the underlying causes of pain and disability between
the two groups.
PMID- 10197167
TI - Intracellular calcium responses to basic calcium phosphate crystals in
fibroblasts.
AB - OBJECTIVE: To examine the intracellular calcium response to basic calcium
phosphate (BCP) crystals in fibroblasts. DESIGN: In this study, intracellular
calcium [Ca2+]i levels in fibroblasts were determined using the photoactive dye,
fura-2. Interruption of these responses was accomplished by either removal of
Ca2+ from the extracellular medium or addition of ammonium chloride that inhibits
intracellular dissolution of BCP crystals by alkalinizing phagolysosomes. The
effects of such interruptions on BCP induction expression of proto-oncogenes were
demonstrated by the Northern blot analysis. RESULTS: Addition of media containing
BCP crystals yielded an immediate 10-fold rise of [Ca2+]i over the baseline level
in human fibroblasts. This peak was derived mostly from extracellular calcium and
was not seen when BCP crystals in calcium-free media were added to fibroblasts.
The [Ca2+]i concentration returned to the baseline level within 8 min. A second
rise of [Ca2+]i started at 60 min and continued to increase up to at least 3 h.
This peak was derived from intracellular dissolution of phagocytosed crystals and
almost completely inhibited by 10 mM ammonium chloride. CONCLUSION: The initial
transient [Ca2+]i increase probably serves as a second messenger leading to
activation of early cellular responses such as c-fos expression which is
important in BCP crystal-induced mitogenesis. The second, slower and more
sustained rise of [Ca2+]i probably initiates other cellular processes needed for
fibroblast mitogenesis.
PMID- 10197168
TI - Matrix degradation by chondrocytes cultured in alginate: IL-1 beta induces
proteoglycan degradation and proMMP synthesis but does not result in collagen
degradation.
AB - OBJECTIVE: To determine the role of interleukin-1 beta (IL-1 beta) in the
degradation of proteoglycans and collagen by articular chondrocytes. DESIGN:
Chondrocytes were cultured in alginate beads for 2 weeks to produce extracellular
matrix, followed by the addition of IL-1 beta for 1 or 2 days. Breakdown of
extracellular matrix (with and without activation of pro-matrix
metalloproteinases (MMPs) by APMA) was monitored by release of glycosaminoglycans
(GAG, proteoglycans) and hydroxyproline (collagen) from the beads into the
medium, and by the amount of damaged collagen in the bead. Levels of (pro)MMPs in
the beads were assayed by zymography and their activity was quantified
fluorometrically. RESULTS: IL-1 beta induced a profound GAG release
(approximately 80% after 2 days at 20 ng/ml IL-1 beta) that was both time and IL
1 beta concentration dependent. Under these conditions no increase in collagen
release or damaged collagen in the bead was detected. Zymography demonstrated
that the synthesis of a variety of proMMPs was induced by IL-1 beta, without a
detectable increase of MMP-activity as measured in the activity assay. After
activation of the proMMPs by APMA, a time and IL-1 beta concentration-dependent
increase in MMP-activity was found, which resulted in almost complete
deterioration of collagen already after 18 h of incubation. In the presence of
APMA, GAG release from IL-1 beta treated beads was significantly increased from
24 to 31%. CONCLUSIONS: Our data suggest that proteoglycan and collagen
degradation are regulated through different mechanisms: IL-1 beta induces the
synthesis of active enzymes that degrade proteoglycans, such as 'aggrecanase',
and inactive proMMPs. Thus, IL-1 beta alone is not sufficient to result in
collagen-degrading MMPs. Once activated, MMPs may account for up to a quarter of
the aggrecan degradation in this model.
PMID- 10197169
TI - Influence of pregnancy on gene expression in rabbit articular cartilage.
AB - OBJECTIVE: Articular cartilage is known to be influenced by estrogen and the
pregnancy-associated hormone, relaxin, in vitro. Such observations have raised
the possibility that articular cartilage in females may be subjected to unique
regulatory influences by such hormones in vivo. The purpose of this study was to
evaluate mRNA levels for several relevant molecules in the articular cartilage of
pregnant and non-pregnant rabbits. DESIGN: Total RNA was extracted from New
Zealand White rabbit knee articular cartilage using the TRIspin method. The total
RNA was reverse transcribed and analysed by the sensitive molecular technique of
semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) using
rabbit specific primer sets. RESULTS: Total RNA yield from articular cartilage
from primigravida rabbits was reduced to 65% of age-matched control values (P =
0.0003); however the yield from multiparous animals was not significantly
depressed. In both cases, DNA yields were not affected by pregnancy. There was a
general tendency for depressed mRNA levels for most genes investigated in
cartilage from pregnant animals. Articular cartilage from multiparous rabbits
showed a significant decrease in mRNA levels for relevant molecules such as type
II collagen, biglycan, collagenase and tissue inhibitors of metalloproteinases
(TIMP)-1, as well as necrosis factor-alpha (TNF-alpha), inducible nitric oxide
synthase (iNOS) and cyclo-oxygenase 2 (COX-2). Transcripts for collagenase and
lumican were significantly lower in cartilage from primigravida rabbits.
Transforming growth factor beta 1 (TGF-beta 1) transcript levels were
significantly decreased in both pregnant groups. In contrast, basic fibroblast
growth factor (bFGF) and insulin-like growth factor-2 (IGF-2) mRNA levels were
significantly decreased in cartilage from primigravida rabbits, whereas
transcripts for these molecules were upregulated in the cartilage of multiparous
rabbits. CONCLUSIONS: The present study demonstrates that regulation of RNA
levels in articular cartilage during pregnancy is complex and is influenced by
the parity and/or the skeletal maturity of the animals.
PMID- 10197170
TI - Longitudinal and cross-sectional variability in markers of joint metabolism in
patients with knee pain and articular cartilage abnormalities.
AB - OBJECTIVE: To determine the within- and between-patient variability in the
concentrations of synovial fluid, serum and urine markers of joint tissue
metabolism in a cohort of patients with knee pain and cartilage changes
consistent with early-stage knee osteoarthritis. DESIGN: Samples of synovial
fluid, serum, and urine were obtained from 52 patients on eight different
occasions during 1 year, as part of a clinical trial in patients with cartilage
abnormalities and knee pain. In joint fluid, aggrecan fragments were quantified
by dye precipitation and enzyme-linked immunosorbent assay (ELISA), and matrix
metalloproteinases-1 and -3, and tissue inhibitor of metalloproteinases-1 by
sandwich ELISAs. In serum, keratan sulfate was quantified by ELISA. Type I
collagen N-telopeptide cross-links in urine were determined by ELISA. RESULTS:
The degree of cross-sectional variability in marker concentrations did not vary
between the different sampling occasions, and did not differ between the periods
of weeks 0 (baseline), 1-4 (treatment) and 13-26 (follow-up). Both between
patient and within-patient coefficients of variation varied for markers in
different body fluid compartments, with the lowest variability for serum keratan
sulfate, followed by urine type I collagen N-telopeptide crosslinks, and the
highest for synovial fluid markers. For synovial fluid, aggrecan fragments showed
the least variability, and matrix metalloproteinases the highest. One patient
with septic arthritis showed a fivefold peak increase in joint fluid aggrecan
fragment concentrations, while the concentration of matrix metalloproteinase-3
increased 100-fold. CONCLUSIONS: Molecular markers of joint tissue metabolism
have been suggested as, for example, outcome measures for clinical trials of
disease-modifying drugs in osteoarthritis. This report is the first to present
data on between- and within-patient variability for such molecular markers in
three different body fluid compartments in stable cohort of patients. The
availability of such data enables calculations to determine the number of
patients needed in prospective studies using these markers as outcome measures.
PMID- 10197171
TI - Longitudinal analysis of the relationship between serum insulin-like growth
factor-I and radiographic knee osteoarthritis.
AB - OBJECTIVE: To examine the relation between serum insulin-like growth factor I
(IGF-I) levels and both incident and progressive radiographic knee osteoarthritis
(OA) in the Framingham Osteoarthritis Study. DESIGN: Subjects had bilateral
weight-bearing, anterior-posterior knee radiographs performed in 1983-1985 and
again in 1992-1993. IGF-I levels were measured from blood specimens obtained in
1988-1989 by a competitive binding radio-immunoassay (RIA) after separation with
octadecasilyl-silica cartridges of serum IGF-I from binding proteins.
Participants without baseline radiographic OA [Kellgren and Lawrence grades (K&L)
= 0-1] were classified as having incident disease if they had K&L > or = 2 grades
at follow-up. Progressive OA was defined as an increase in K&L score of > or = 1
in knees with baseline OA (K&L > or = 2). All analyses were knee-based and sex
specific. We examined IGF-I tertiles in relation to the risk of incident and
progressive radiographic OA separately, adjusting for age, body mass index (BMI),
and baseline K&L score, and used generalized estimating equations to adjust for
the correlation between fellow knees. RESULTS: Four hundred and forty-one
participants had knee radiographs and serum IGF-I levels measured. No
associations were found for serum IGF-I levels and incident [women: OR = 0.9 (0.6
1.7), men OR = 1.2 (0.6-2.6)] or progressive [women OR = 0.9 (0.6-1.6), men OR =
0.9 (0.3-3.0)] radiographic knee OA in either sex. Neither did we observe any
association between IGF-I and worsening of individual radiographic features of OA
(i.e., osteophyte growth and joint space loss). CONCLUSION: In summary, this
longitudinal study did not demonstrate any association of serum IGF-I and
incident or progressive radiographic knee OA. Further studies are needed to
clarify the role of IGF-I in OA.
PMID- 10197172
TI - Osteoporosis: review of the evidence for prevention, diagnosis and treatment and
cost-effectiveness analysis. Executive summary.
AB - This report describes evidence for the diagnosis, prevention, and treatment of
osteoporosis in postmenopausal healthy white women. Osteoporosis is becoming an
increasingly important public health problem as our population ages. Although it
is partially preventable, fractures related to osteoporosis are still common.
Because of the economic and social burdens, comprehensive prevention programs are
needed. Insufficient data prevent development of comparable analyses for men or
nonwhite women. Discussed are the effectiveness, risks, and costs of diagnostic
tests and treatments, the probabilities that women will have osteoporosis-related
fractures, and the effects of various factors on these probabilities. Hormone
replacement therapy is considered most cost-effective; women who refuse hormone
replacement can consider bisphosphonates (alendronate) and calcitonin. Nomograms
are presented for guiding treatment and testing decisions for individual
patients. The following public health measures are recommended: Ensure that
adults receive the optimal daily intake of calcium--between 1000 mg and 1500 mg;
ensure that people at risk for vitamin D deficiency receive 400 IU to 800 IU of
vitamin D daily; inform people that exercise, in addition to its other benefits,
should help prevent osteoporosis; and discourage people from smoking.
PMID- 10197173
TI - Osteoporosis: review of the evidence for prevention, diagnosis and treatment and
cost-effectiveness analysis. Introduction.
PMID- 10197174
TI - Calcium and vitamin D are effective in preventing fractures in elderly people by
reversing senile secondary hyperparathyroidism.
PMID- 10197175
TI - Secondary hyperparathyroidism in the elderly: means to defining hypovitaminosis
D.
PMID- 10197176
TI - Prevalence of subclinical vitamin D deficiency in different European countries.
PMID- 10197177
TI - Vitamin D metabolism and action.
PMID- 10197178
TI - How about vitamin D receptor polymorphisms?
PMID- 10197179
TI - Vitamin D requirements for humans of all ages: new increased requirements for
women and men 50 years and older.
PMID- 10197180
TI - Vitamin D and calcium: recommended intake for bone health.
PMID- 10197181
TI - Vitamin D deficiency and osteopathies.
PMID- 10197182
TI - Vitamin D and its metabolites in the treatment of osteoporosis.
PMID- 10197183
TI - Effects of calcium and vitamin D insufficiency on the skeleton.
PMID- 10197184
TI - Illusions and reality-checking on the small screen.
PMID- 10197185
TI - Light and sight since antiquity.
AB - Light and sight were not distinguished from one another until the dioptrics and
the anatomy of the eye had been adequately described in the seventeenth century.
A survey of early theories of light is presented, together with descriptions of
developing knowledge of ocular anatomy. Once the analogy between the eye and a
camera had been made, the problem of accommodation was exposed, and corrections
for errors of refraction could be given theoretical support. Theories of
accommodation in the seventeenth and eighteenth centuries are briefly reviewed,
as is the early history of eye glasses.
PMID- 10197186
TI - Illumination-induced apparent shift in orientation of human heads.
AB - Changing the position of a light source illuminating a human face induces an
apparent shift of the perceived orientation of that face. The direction of this
apparent shift is opposite to the shift of the light source. We demonstrated the
illumination-induced apparent orientation shift (IAOS), quantified it in terms of
the physical orientation shift needed to compensate for it, and evaluated the
results in the context of possible mechanisms underlying orientation judgment.
Results indicate that IAOS depends not only on the angle between the two light
source positions, but also on the mean orientation of the face. Availability of
cues coded in the visual texture of the face did not affect IAOS. The most
effective cue was the location of the visible outline of the face. IAOS seems to
be due to a shift of this outline when shadowed areas on the face merge with the
black background. We conclude that an important mechanism for orientation
judgment is based on a comparison of visible parts left and right of the profile
line.
PMID- 10197187
TI - Perceptual, oculomotor, and neural responses to moving color plaids.
AB - Moving plaids constructed from two achromatic gratings of identical luminance
contrast are known to yield a percept of coherent pattern motion, as are plaids
constructed from two identical chromatic (e.g. isoluminant red/green) gratings.
To examine the interactive influences of chromatic and luminance contrast on the
integration of visual motion signals, we constructed plaids with gratings that
possessed both forms of contrast. We used plaids of two basic types, which
differed with respect to the phase relationship between chromatic and luminance
modulations (after Kooi et al, 1992 Perception 21 583-598). One plaid type
('symmetric') was made from component gratings that had identical
chromatic/luminance phase relationships (e.g. both components were red
bright/green-dark modulation). The second plaid type ('asymmetric') was made from
components that had complimentary phase relationships (i.e. one red-bright/green
dark grating and one green-bright/red-dark grating). Human subjects reported that
the motion of symmetric plaids was perceptually coherent, while the components of
asymmetric plaids failed to cohere. We also recorded eye movements elicited by
both types of plaids to determine if they are similarly affected by these image
cues for motion coherence. Results demonstrate that, under many conditions, eye
movements elicited by perceptually coherent vs noncoherent plaids are
distinguishable from one another. To reveal the neural bases of these perceptual
and oculomotor phenomena, we also recorded the responses of neurons in the middle
temporal visual area (area MT) of macaque visual cortex. Here we found that
individual neurons exhibited differential tuning to symmetric vs asymmetric
plaids. These neurophysiological results demonstrate that the neural mechanism
for motion coherence is sensitive to the phase relationship between chromatic and
luminance contrast, a finding which has implications for interactions between
'color' and 'motion' processing streams in the primate visual system.
PMID- 10197188
TI - Measurement of the texture-coherence limit for bandpass arrays.
AB - Casual observation suggests that when the elements of a visual array are packed
at a sufficiently high density they cohere to generate the percept of a texture.
This 'texture-coherence limit' has been quantified by using arrays composed of
Gabor functions, sixth Gaussian derivatives, or differences of Gaussians. In all
cases the texture-coherence limit was a power-law function of the size of the
elements as quantified by their space constants with an exponent averaging 0.7.
Furthermore, the texture-coherence limit was independent of both element spatial
frequency and contrast over a considerable range. A quantitative fit to the data
is provided by a model in which the texture-coherence limit is determined by
activation of complex cells, which pool a spatial range of subunit inputs,
throughout the stimulus region. Possible extensions to two dimensions are
considered.
PMID- 10197189
TI - Spatial-frequency discrimination, brain lateralisation, and acute intake of
alcohol.
AB - The effect of alcohol (breath-alcohol level of 0.1%) on perceptual discrimination
of low (1.5 cycles deg-1) and high (8 cycles deg-1) spatial frequencies in the
left and right visual field was measured in eighteen right-handed males, in a
double-blind, balanced placebo design. Discrimination thresholds for briefly (180
ms) presented sinusoidal gratings were determined by two-alternative forced
choice judgments with four interleaving psychophysical staircases providing
random trial-to-trial variation of reference spatial frequency and visual field,
in addition to a random (+/- 10%) jitter of reference spatial frequency. Alcohol
produced overall higher discrimination thresholds but did not alter the visual
field balance: no main effect of visual field was observed, but in both placebo
and alcohol conditions spatial frequency interacted with visual field in the
direction predicted by the spatial-frequency hypothesis of hemispheric asymmetry
in visual-information processing, with left-visual-field/right-hemisphere
superiority in discrimination of low spatial frequencies and right-visual
field/left-hemisphere superiority in discrimination of high spatial frequencies.
PMID- 10197190
TI - Haptic underestimation of angular extent.
AB - To what extent can individuals accurately estimate the angle between two surfaces
through touch alone, and how does tactile judgment compare to visual judgment?
Subjects' ability to estimate angle size for a variety of haptic and visual
stimuli was examined in a series of nine experiments. Triangular wooden blocks
and raised contour outlines comprising different angles and radii of curvature at
the apex were used in experiments 1-4 and it was found that subjects consistently
underestimated angular extent relative to visual baselines and that the degree of
underestimation was inversely related to the actual size of the angle. Angle
estimates also increased with increasing radius of curvature when actual angle
size was held constant. In contrast, experiments 5-8 showed that subjects did not
underestimate angular extent when asked to perform a haptic-visual match to a
computerized visual image; this outcome suggests that visual input may
'recalibrate' the haptic system's internal metric for estimating angle. The basis
of this cross-modal interaction was investigated in experiment 9 by varying the
nature and extent of visual cues available in haptic estimation tasks. The
addition of visual-spatial cues did not significantly reduce the magnitude of
haptic underestimation. The experiments as a whole indicate that haptic
underestimations of angle occur in a number of different stimulus contexts, but
leave open the question of exactly what type of visual information may serve to
recalibrate touch in this regard.
PMID- 10197191
TI - Stiff-man syndrome.
PMID- 10197192
TI - Amiodarone-induced cornea verticillata.
PMID- 10197193
TI - Cardiology questions for the MRCP (UK) examination.
PMID- 10197194
TI - Cutaneous sarcoidosis.
AB - Sarcoidosis is a multi-organ granulomatous disorder of unknown cause. Skin
sarcoidosis occurs in about 25% of patients with systemic disease and may also
arise in isolation. A wide range of clinical presentations of cutaneous
sarcoidosis is recognised. The diagnosis rests on the presence of non-caseating
granulomas on skin biopsy and the exclusion of other granulomatous skin disease.
The treatment and overall prognosis of cutaneous sarcoidosis is primarily
dependent on the degree of systemic involvement. In patients with aggressive
disease limited to the skin immunosuppressive therapy may be indicated.
PMID- 10197195
TI - Barrett's oesophagus.
AB - Barrett's oesophagus represents the replacement of stratified squamous epithelium
by metaplastic columnar epithelium for 3 cm of the distal oesophagus. Gastro
oesophageal reflux, which affects 40% of the adult population, is the principal
aetiological factor. This results in predominantly acid but also bile reflux (due
to duodenogastrooesophageal reflux) through the lower oesophageal sphincter,
transient relaxation of which accounts for the main mechanism of reflux.
Conventional Barrett's oesophagus is reported in 11-13% of patients with
symptomatic reflux and short segment Barrett's oesophagus (< 3.0 cm) in 18%.
Approximately 50% of these patients have recognised complications on
presentation, eg, carcinoma (15%). The disparity between clinical symptoms and
endoscopic severity is due to reduced oesophageal mucosal sensitivity as a
consequence of prolonged mucosal acid exposure. These rather alarming figures
combined with the knowledge that Barrett's oesophagus is a pre-malignant
condition (the diagnosis is associated with a 25-130-fold increase of malignancy)
may account for the substantial increase in junctional gastrooesophageal
malignancies. Symptomatic Barrett's oesophagus should be managed with full-dose
proton pump inhibitors, eg, lansoprazole. Anti-reflux surgery should be reserved
for the medically fit patient with recurrent symptomatic relapse in the
histological absence of premalignant change. There is no evidence suggesting that
surgery can be used as a prophylactic measure against malignancy. Encouraging
short-term results have been obtained with photodynamic therapy in the management
of high-grade dysplasia. However, columnar epithelium has been found underlying
the regenerated squamous epithelium, suggesting that life-long surveillance is
warranted.
PMID- 10197196
TI - Recent advances in the drug treatment of heart failure.
AB - A number of important questions surrounding the treatment of systolic congestive
heart failure have been answered by randomised clinical trials completed within
the past 2 years. In particular, these studies have established that high-dose
angiotensin-converting enzyme (ACE) inhibition is more beneficial than low dose
therapy, and that angiotensin II receptor antagonists are an acceptable
alternative in patients unable to tolerate ACE inhibitors. Digoxin has been shown
to be the only inotropic agent not associated with increased mortality, while
amiodarone exerts a modest survival benefit in arrhythmiaprone patients. Beta
blockers appear to be beneficial for selected patients although their precise
role remains to be defined by ongoing studies.
PMID- 10197197
TI - Does psychological intervention help chronic skin conditions?
AB - The objective of the study was to assess the impact of psychological/psychiatric
assessment in patients with chronic or intractable dermatological conditions. A
diagnostic interview was undertaken in order to pin-point any temporal connection
between an adverse life-event and the first appearance of the skin disorder.
Following this, the dermatologist's assessment of subsequent changes in the skin
disorder were noted. The three main dermatological diagnoses were atopic eczema
(10), prurigo (10), and psoriasis (nine). Follow-up was for up to 5 years. A
favourable response was noted in 40 out of the 64 patients who participated in
the study; this was usually evident within a few weeks and maintained thereafter.
Remission was achieved in 12, while 28 showed some improvement. We conclude that
this liaison between dermatology and psychiatry proved a valuable adjunct to
normal dermatological treatment and was followed by improvement in the majority
of patients.
PMID- 10197198
TI - Copper, zinc, and magnesium levels in non-insulin dependent diabetes mellitus.
AB - A relationship has been reported between trace elements and diabetes mellitus.
This study evaluated the role of such a relationship in 83 patients with non
insulin dependent diabetes mellitus (40 men and 43 women), with a mean duration
of diabetes of 3.9 +/- 3.6 years. Patients with nephropathy were excluded. Thirty
healthy non-diabetic subjects were studied for comparative analysis. Subjects
were subdivided into obese and non-obese. Diabetic subjects were also subdivided
into controlled and uncontrolled groups; control was based on fasting blood
glucose and serum fructosamine levels. Plasma copper, zinc and magnesium levels
were analysed using a GBC 902 double beam atomic absorption spectrophotometer.
Plasma zinc and magnesium levels were comparable between diabetic and non
diabetic subjects, while copper levels were significantly elevated (p < 0.01) in
diabetic patients. Age, sex, duration and control of diabetes did not influence
copper, zinc, or magnesium concentrations. We conclude that zinc and magnesium
levels are not altered in diabetes mellitus, but the increased copper levels
found in diabetics in our study may merit further investigation of the
relationship between copper and non-insulin dependent diabetes mellitus.
PMID- 10197199
TI - Management of inguinal herniae in patients on continuous ambulatory peritoneal
dialysis: an audit of current UK practice.
AB - Patients receiving continuous ambulatory peritoneal dialysis are at increased
risk for the development of inguinal herniae, with a reported prevalence of 14%.
Elective hernia repair is indicated for these patients as strangulation is
associated with a high mortality in this population. There are currently no
national guidelines relating to the optimal peri-operative management of these
patients, in particular the appropriate pre- and post-operative dialysis regimen.
The aim of the current study was to evaluate current practice in the UK by means
of a postal questionnaire sent to all centres undertaking renal transplantation.
Replies were received from 34/37 centres. The principal study finding was the
wide variation in surgical practice between different centres with regard to pre-
and post-operative dialysis regimes. Only 44% of centres had an established
protocol. Based upon the study findings we have devised a protocol that we hope
to see implemented into UK practice. Following its introduction, a re-assessment
will be performed and the audit cycle completed.
PMID- 10197200
TI - A patient with recurrent sweating.
PMID- 10197201
TI - The young woman who could not stop vomiting.
PMID- 10197202
TI - Painful hips in a patient on long-term steroid treatment.
PMID- 10197203
TI - Cutaneous vasculitis and collapse.
PMID- 10197204
TI - An unusual cause of pulmonary hypertension and right heart failure.
PMID- 10197205
TI - Progressive neurological symptoms in a diabetic patient.
PMID- 10197206
TI - Chronic fatigue syndrome.
PMID- 10197207
TI - Asymptomatic murmurs.
PMID- 10197208
TI - The use of the Internet amongst gastroenterology out-patients.
PMID- 10197209
TI - Compression syndromes caused by substernal goitres.
PMID- 10197210
TI - Anaphylactoid reaction to hydroxycobalamin with tolerance of cyanocobalamin.
PMID- 10197211
TI - Salvage angioplasty following failed thrombolysis.
PMID- 10197212
TI - Images in medicine. Foreign body aspiration.
PMID- 10197213
TI - Myocardial infarction in a pre-menopausal woman with angiographically normal
coronary arteries.
AB - A young pre-menopausal non-drug-addict woman without risk factors for coronary
artery disease suffered from a non-Q-wave acute myocardial infarction. She
presented with epigastric pain and vomiting. Diagnosis of acute myocardial
infarction was not suspected at first because of her young age and lack of risk
factors. She was treated for gastritis but worsening of epigastric pain and its
radiation to chest warranted the diagnosis of acute myocardial infarction, which
was confirmed by serial serum cardiac enzymes. Subsequent coronary angiogram
revealed normal coronary arteries.
PMID- 10197214
TI - Sudden death associated with group A streptococcal infection in an 8-year-old
girl with undiagnosed hypertrophic cardiomyopathy.
AB - An 8-year-old girl died suddenly without prior symptoms. Post-mortem examination
identified both systemic group A streptococcal infection and hypertrophic
cardiomyopathy. She had no history of cardiac symptoms and was not in a high-risk
group for sudden death due to hypertrophic cardiomyopathy. We believe the
disseminated but asymptomatic group A streptococcal infection precipitated her
early death from hypertrophic cardiomyopathy. Sudden unexpected death during
systemic infection should be followed by post-mortem examination to look for
evidence of hypertrophic cardiomyopathy, as this diagnosis has genetic
implications for other family members.
PMID- 10197215
TI - Systemic activity of inhaled and swallowed beclomethasone dipropionate and the
effect of different inhaler devices.
AB - Inhaled glucocorticoids such as beclomethasone dipropionate, which are used in
the treatment of asthma, may be associated with systemic adverse effects. To
determine whether any systemic absorption following the inhalation of
beclomethasone was a result of drug being absorbed from the lung (inhaled
fraction) or the gastrointestinal tract (swallowed fraction), we studied normal
subjects after the inhalation or swallowing of 2 mg beclomethasone dipropionate.
Systemic activity was assessed using early morning cortisol suppression. Both
inhaled and swallowed fractions produced significant systemic activity, the
degree of which depended on the inhaler device used. Systemic activity was
greater using a dry powder inhaler (52%) than using a metered dose inhaler with a
large volume spacer (28%). These findings suggest that to limit potential adverse
effects from high-dose beclomethasone dipropionate it is better to use a metered
dose aerosol with large volume spacer than a dry powder.
PMID- 10197216
TI - Clostridium difficile-associated diarrhoea.
AB - At our hospital, the number of cases of Clostridium difficile-associated
diarrhoea increased from 29 in 1993 to 210 in 1995. The case notes of 110
patients with C difficile-associated diarrhoea during the first 6 months of 1995
were analysed retrospectively. The majority of the patients (106) had received
antibiotics before the onset of diarrhoea; 46 had received three or more
different antibiotics and 28 had received metronidazole. In 19 patients, the
first stool sample after the onset of diarrhoea was negative for C difficile
cytotoxin, with a mean delay of 8.2 days before a positive stool sample. We
conclude that C difficile-associated diarrhoea was associated with the usage of
multiple antibiotics, and that metronidazole did not protect against colonisation
by C difficile. We also recommend that more than one stool sample should be
tested for the C difficile cytotoxin.
PMID- 10197217
TI - Spontaneous haemothorax: a cause of sudden death in von Recklinghausen's disease.
AB - Vasculopathy is a relatively frequent but poorly recognised manifestation of von
Recklinghausen's neurofibromatosis. One of its more dramatic presentations is as
spontaneous haemothorax. Clinicians and pathologists should be aware of this
syndrome as a cause of sudden death in patients with neurofibromatosis.
PMID- 10197218
TI - The best management for 'crescendo biliary colic' is urgent laparoscopic
cholecystectomy.
AB - Gallbladder disease due to stones is well recognised as falling into two
categories, presenting with either chronic symptoms or developing acute
cholecystitis or other complications. We describe an intermediate group of 14
patients (11 women, three men, median age 31 years) presenting with 4-14 days of
at least daily attacks of resolving biliary colic, who underwent early
laparoscopic cholecystectomy within 24 hours of presentation. None had any
evidence of acute inflammation, either at laparoscopy or on histology. Their
surgery was straightforward with operating times ranging from 35-80 minutes and
no complications. Patients with 'crescendo biliary colic' are often young women
who can rarely afford invalidity. Rather than the current practice of analgesia
for each attack and elective surgery weeks later, they are optimally managed by
urgent laparoscopic cholecystectomy, preventing the development of complications
and minimising the need for further medical involvement.
PMID- 10197219
TI - Generalised wasting in a young diabetic.
PMID- 10197221
TI - Fits and starts.
PMID- 10197220
TI - Orthostatic hypotension in an elderly patient.
PMID- 10197222
TI - Genetic polymorphism of the angiotensin-converting enzyme (ACE) in asthmatic
patients.
AB - Angiotensin-converting enzyme (ACE) inactivates bradykinin, substance P and
neurokinin A, which are believed to play important roles in the pathogenesis of
asthma, especially in neurogenic inflammation. It has recently been shown that an
insertion (I)/deletion (D) polymorphism in the ACE gene accounts for variation in
serum ACE levels. There are thus three genotypes (insertion homozygote, II;
deletion homozygote, DD; heterozygotes, DI). The serum ACE level with the DD type
is reported to be about double that of the II type and intermediate in the DI
case. In the present study, we examined whether asthma is linked with this ACE
gene polymorphism. Seventy-one patients with asthma (27 males and 44 females) and
142 sex- and age-matched healthy controls were determined for their genotype by
the polymerase chain reaction (PCR) method. Twenty-five asthmatics demonstrated
the II type (35.2%), 37 the DI type (52.1%), and nine the DD type (12.7%). There
were no significant differences in the distributions of genotypes and serum ACE
levels between healthy controls and patients. No significant differences were
evident in serum IgE levels, age at onset, proportion of atopic type patients and
severity of asthma among the three genotypes. We did not find any association
between asthma and the ACE gene polymorphism in this study.
PMID- 10197223
TI - Non-invasive home ventilation in patients over 75 years of age: tolerance,
compliance, and impact on quality of life.
AB - The adequacy of domiciliary non-invasive positive pressure ventilation (NIHV) for
hypercapnic restrictive pulmonary disease in patients aged 75 years or above has
been questioned, because of a lower life expectancy, a higher risk of
neuropsychological impairment and a lower potential for adapting to NIHV. This
study aims to illustrate that the use of NIHV is possible and efficient in this
age group. In our referral area, all patients under NIHV have been included in a
database since 1994; at the end of 1996, all patients in whom NIHV had been
initiated at age 75 years or above were studied. We performed a cross-sectional
study of six patients (two men, four women, age: 79 +/- 3 years at time of study)
who had been under NIHV for 31 +/- 17 months. Patients underwent pulmonary
function testing, assessment of respiratory muscle strength, physical disability
and neuropsychological performance, tolerance and compliance to NIHV, and health
related quality of life (SF-36, St. George Respiratory Questionnaire: SGRQ).
Hospitalization rates were recorded for the year prior and the 2 yr following
initiation of NIHV. By the time of the study, all patients showed improved
arterial blood gases when compared to values before NIHV (PaCO2: 46 +/- 9 vs 66
+/- 10 mmHg, P = 0.04). Patients adapted well to NIHV, with minor side-effects
and an average daily use of ventilator of 10.5 +/- 2 h. None of the patients
showed signs of emotional disturbance. SF-36 scores for mental health, subjective
well-being and vitality, or social functioning, did not differ from that of age
matched controls. SGRQ scores were similar to those published for younger
patients under NIHV. Use of health care facilities was similar to that of younger
patients under NIHV; hospitalization rates decreased significantly after
initiating NIHV (40 +/- 31 days for year before NIHV, vs 13 +/- 14 days and 0.8
+/- 0.4 days for the 2 yr following NIHV, P = 0.02). Age above 75 years should
not be considered per se as a contraindication to NIHV in patients with well
accepted indications for this treatment. Our results suggest that in this age
group, the cost/benefit ratio of NIHV may be favourable.
PMID- 10197224
TI - Effects of severity of long-standing congestive heart failure on pulmonary
function.
AB - To investigate the effects of severity of long-standing congestive heart failure
(CHF) on pulmonary function, we studied 53 (47 men) consecutive patients, all
heart transplant candidates. Their mean (+/- SD) age and ejection fraction were
47 +/- 12 years and 23 +/- 7%, respectively. All patients underwent spirometry,
lung volume, diffusion capacity (DLCO), maximum inspiratory (PImax) and
expiratory pressure (PEmax) measurement. Maximum cardiopulmonary exercise test on
a treadmill was also performed to determine maximum oxygen consumption (VO2max).
On the basis of VO2max, the patients were then divided into those with a VO2max >
14 ml min-1 kg-1 (group 1, n = 30) and those with a VO2max < or = 14 ml min-1 kg
1 (group 2, n = 23). In comparison with group 1, group 2 patients had lower
FEV1/FVC (70 +/- 8% vs 75 +/- 7%, P = 0.008), lower FEF25-75 (46 +/- 21 vs 70 +/-
26%pred, P < 0.001), lower TLC (76 +/- 15 vs 85 +/- 13%pred, P = 0.02) and lower
PImax (68 +/- 20 vs 87 +/- 22 cmH2O, P = 0.003), but comparable DLCO (84 +/- 15
vs 88 +/- 20%pred, P = N.S.), and PEmax (99 +/- 25 vs 96 +/- 22 cmH2O, P = N.S.).
In conclusion, our data suggest that respiratory abnormalities, such as
restrictive defects, airway obstruction, and inspiratory muscle weakness, are
more pronounced in patients with severe CHF than in those with mild-to-moderate
disease. Further studies are required to investigate the extent to which these
abnormalities contribute to dyspnoea during daily activities in patients with
heart failure.
PMID- 10197225
TI - Different expression of integrins by mononuclear phagocytes in peripheral blood
and bronchoalveolar lavage fluid.
AB - Alveolar macrophages (AM) originate from blood monocytes and, during the
maturation process, undergo functional and morphological changes which are also
reflected in their phenotypic pattern. Among the macrophage membrane antigens,
adhesion molecules of the integrin family are particularly important for effector
functions and cell-cell interactions. The aim of this study was to analyse the
membrane expression of selected integrins by AM recovered from bronchoalveolar
lavage (BAL) as compared to their precursors, peripheral blood monocytes (PBM).
The cells were stained using a sensitive immunoperoxidase assay with 10 different
monoclonal antibodies. The data showed a higher expression by AM than PBM of all
but one of the studied adhesion molecules. The only exception was CD11b (Mac-1,
CR3) which showed a higher expression in PBM than in AM. Several molecules, for
example, CD49d (VLA-4), CD51 (vitronectin receptor), and CD54 (intercellular
adhesion molecule-1, ICAM-1) were found to be upregulated by AM in patients with
a lymphocytic pattern of BAL. In contrast, the phenotype of PBM does not show any
changes in these patients. In conclusion, we have demonstrated differences in the
expression of integrins between AM and PBM which can be partially responsible for
some of their functional differences.
PMID- 10197226
TI - Effects of hypoxia on renal hormonal balance in normal subjects and in patients
with COPD.
AB - There is a complex interaction between pulmonary haemodynamics, hormonal, and
salt and water balance in patients with chronic obstructive pulmonary disease
(COPD) and in normal subjects exposed to hypoxia or high altitude. This study
aims to investigate the effects of hypoxia on renal hormonal balance in normal
subjects and patients with COPD, particularly the role of urinary dopamine and
atrial natriuretic peptide (ANP). Urinary dopamine output, ANP, and plasma renin
activity (PRA) were measured in 12 normal subjects exposed to hypoxia (12% O2)
and hyperoxia (40% O2) for 1 h and in 15 patients with exacerbations of COPD
while breathing air or O2. These measurements were repeated in six of the
patients with exacerbations of COPD when they were clinically stable. Hypoxia
caused an increase in ANP levels (49 +/- 6-62 +/- 6 pg ml-1, P < 0.05) and a fall
in urinary dopamine output (277 +/- 39-205 +/- 33 ng h-1, P < 0.002) in normal
subjects. Hyperoxia was associated with a return of plasma ANP to the baseline
values. In patients with exacerbations of COPD plasma ANP levels were higher (181
+/- 36 pg ml-1) than in normal subjects (49.5 +/- 6.5 pg ml-1, P < 0.001).
Urinary dopamine output breathing air (175 +/- 34 ng h-1) was similar to the
levels when normal subjects were made hypoxaemic and PRA was elevated in
comparison to normal values. There was no change in their levels following the
acute administration of oxygen in patients presenting with exacerbations of COPD,
but oxygen improved urinary sodium excretion (P < 0.05). In six patients re
studied when clinically stable there was a fall in urinary dopamine output,
plasma ANP and PRA when breathing air in comparison to the acute stage of the
disease (P < 0.05). These data suggest presence of renal hormonal imbalance
including endogenous urinary dopamine output during hypoxic exacerbation of COPD
and in normal subjects exposed to hypoxia.
PMID- 10197227
TI - Prevalence of obstructive lung diseases and respiratory symptoms in southern
Sweden.
AB - The prevalence of obstructive lung diseases is increasing in Scandinavia and
worldwide. The reasons for this are not known. The prevalence varies between
countries but also between different areas within the same country. In northern
Europe a north-south gradient and also an east-west gradient have been proposed.
To our knowledge this is the first comprehensive epidemiological study concerning
obstructive lung diseases and respiratory symptoms in the southern part of
Sweden. The prevalence of bronchial asthma, chronic bronchitis/emphysema,
respiratory symptoms, smoking habits and medication in a random sample of 12,071
adults aged 20-59 years was assessed in a postal survey with a slightly modified
questionnaire previously used in central and northern Sweden (the OLIN Studies).
The questionnaire was based on the British Medical Research Council (BMRC)
questionnaire. We also compared the prevalence figures of asthma found in the
postal survey with those reported in the medical records in a part of the study
area. After two reminders, the response rate was 70.1% (n = 8469); 33.8% of the
responders were smokers. Among younger (20-39 year age group) individuals,
smoking was most common in women, whereas in those aged 40-59 years, smoking was
more common in men. In all, 469 subjects (5.5%) stated that they had asthma,
41.6% of whom reported a family history of asthma compared to 15.9% of the study
sample not reporting asthma. Of all subjects reporting asthma, 60.1% (n = 282)
answered that they used asthma drugs. Inhaled steroids were used by 20.7%.
Chronic bronchitis and/or emphysema was reported by 4.6% (n = 392), 28.6% of whom
reported a family history of chronic bronchitis or emphysema compared to 6.8% of
the study sample not reporting chronic bronchitis. The most common respiratory
symptom in the study population was 'phlegm when coughing' reported by 15.1% (n =
1279). Our data show a prevalence of self-reported asthma of 5.5% compared with
7% reported by Lunback et al. in northern Sweden, which indicates a north-south
gradient.
PMID- 10197228
TI - A comparison of the onset of action of salbutamol and formoterol in reversing
methacholine-induced bronchoconstriction.
AB - This single-centre, randomized, double-blind, double-dummy four-way cross-over
study in 24 moderately severe asthmatic patients compared the speed of onset of
recommended doses of salbutamol (200 micrograms) and formoterol (12 micrograms)
delivered by metered-dose inhaler in reversing the bronchoconstriction induced by
a cumulative dose of methacholine to produce a 20% decrease (PD20) in forced
expiratory volume in 1 s (FEV1). Specific airway conductance (SGAW) and airway
resistance (RAW) were measured in baseline condition, immediately after challenge
and 0.5, 1.5, 3, 5, 10, 15, 30, 60 min and every hour up to 4 h after inhalation
of the trial drug. FEV1 was measured in baseline condition, after challenge and
15, 30 and 60 min and then every 30 min up to 4 h after inhalation of the study
drug. The primary efficacy parameter was the change in SGAW. Salbutamol produced
a two-fold increase in SGAW within 4 min and a maximum increase after 79.3 min.
Formoterol produced a two-fold increase in SGAW after 5 min and a maximum
increase after 119.6 min. Changes in SGAW were slightly, but consistently, higher
during the first 2 h after inhalation of salbutamol, both in absolute values and
as a percentage of the maximum response. Differences were significant at 10, 15
and 30 min time points. There was no significant difference between the maximum
values of SGAW after the two drugs. Changes in RAW and FEV1 reflected the
differences in SGAW. It was concluded that in methacholine-induced
bronchoconstriction both formoterol and salbutamol have a very fast onset of
action, achieving prechallenge values of SGAW within 3 min, salbutamol being
slightly faster than formoterol.
PMID- 10197229
TI - Asthma-related prescribing patterns with four different corticosteroid inhaler
devices.
AB - Four types of corticosteroid inhaler devices are available in New Zealand for
first-line treatment of asthma, including two aerosol systems [Autohaler (3M
Healthcare Ltd, Loughborough, U.K.; 3M Pharmaceuticals (Australia Pty Ltd,
Sydney, Australia) and MDI (Glaxo Wellcome PLC, Ware, U.K.)] and two dry powder
systems [Diskhaler (Glaxo Wellcome) and Turbuhaler (Astra AB, Sodertalje,
Sweden)]. Rates of asthma-related health care consumption and treatment outcomes
associated with use of the different inhalers are unknown. In this retrospective
survey, asthma-related primary health care consultation and prescription patterns
were compared in a large general practice population for each corticosteroid
inhaler device prescribed as first-line treatment. An electronic search of a
computerized clinical database yielded the medical records of 5704 patients with
physician-diagnosed asthma who were prescribed either the Autohaler, Diskhaler,
MDI or Turbuhaler as their sole corticosteroid inhaler device in the previous 12
months. The mean daily inhaled corticosteroid dose was lowest for the Autohaler
(569 micrograms day-1; 95% CI: 538-605), followed by the Diskhlaer (638
micrograms day-1; 95% CI: 609-670) and MDI (665 micrograms day-1; 95% CI: 638
673), and was highest for the Turbuhaler (990 micrograms day-1; 95% CI: 954-1029,
P < 0.001). A relatively high proportion of patients aged 19-49 years in the
Turbuhaler and Diskhaler groups (29% and 23%, respectively) received at least one
inhaled corticosteroid prescription including a daily dose greater than 1500
micrograms compared with the MDI group (4%). In the Diskhaler group the mean
daily inhaled corticosteroid dose prescribed for adult patients was similar to
that for the Turbuhaler group (904 micrograms day-1 and 1058 micrograms day-1,
respectively). These data suggest that in New Zealand the dry powder
corticosteroid inhaler devices are prescribed for adults at significantly higher
doses than the aerosol inhaler devices. Clinical databases of this type yield
valuable information on drug utilization in large patient populations and
usefully assess clinical prescribing practices.
PMID- 10197230
TI - Effect of single doses of inhaled lignocaine on FEV1 and bronchial reactivity in
asthma.
AB - Inhaled lignocaine appeared to have considerable steroid sparing properties in an
uncontrolled trial in 20 patients with oral-steroid-dependent asthma. Since it
can also cause bronchoconstriction, safety needs to be studied under controlled
conditions. We have performed a randomized, double-blind, placebo-controlled
study in 20 patients with mild to moderate asthma to determine the effects of
single doses of inhaled lignocaine 40 and 160 mg compared to saline. Saline and
lignocaine 40 and 160 mg caused an initial fall in FEV1, mean maximum change
being 0.13, 0.19 and 0.231 respectively with no significant difference between
treatments (P = 0.2). There was no fall in FEV1 following salbutamol pretreatment
and lignocaine had no significant effect on heart rate or blood pressure or on
bronchial reactivity to methacholine carried out at 90 min after inhalation.
These results show that single doses of inhaled lignocaine are well tolerated in
subjects with mild to moderate asthma and that any tendency to
bronchoconstriction can be prevented with salbutamol pretreatment.
PMID- 10197231
TI - Pulmonary adenomatoid malformation presenting as unilobar cysts in an adult.
PMID- 10197232
TI - Hypersensitivity pneumonitis probably caused by cyclosporine. A case report.
PMID- 10197233
TI - Alglucerase treatment of type 1 Gaucher disease with pulmonary involvement.
PMID- 10197234
TI - Benign tumors and tumor-like lesions of the adult kidney. Part I: Benign renal
epithelial neoplasms.
AB - The spectrum of renal neoplasms has expanded in recent years. Although most of
the work taking place in this field has concerned malignant neoplasms of the
kidney, there have been significant improvements in our knowledge of benign renal
tumors and tumor-like lesions, especially in renal cell adenoma, renal
oncocytoma, and renal angiomyolipoma. Awareness and knowledge of these benign
lesions is important because they are often included in the differential
diagnoses of malignant tumors, with which they may be confused both clinically
and pathologically. The authors review the topic of benign renal neoplasms and
tumor-like lesions that occur in adults, emphasizing some of the newly described
aspects of these lesions.
PMID- 10197235
TI - Melan-A, a new melanocytic differentiation marker.
AB - Melan-A/MART-1 is a recently identified new melanocytic differentiation marker,
which is recognized as an antigen on melanoma cells by cytotoxic T-lymphocytes.
It is of interest for clinicians as potential immunotherapeutic target and it is
relevant for pathologists as a novel diagnostic marker, since two antibodies
(A103 and M2-7C10) have become available to study Melan-A/MART-1 expression on
archival material. Both antibodies are useful in the differential diagnosis of
melanocytic tumors, especially metastatic tumors, since they are more sensitive
than HMB-45. Both antibodies are also of diagnostic value in the recognition of
perivascular epithelioid cell tumors (angiomyolipoma, lymphangioleiomyomatosis,
and clear cell tumor). Since A103 has the unique property of staining many
steroid hormone producing cells, this antibody is also of value for the
recognition of tumors derived from these cells, such as adrenocortical
carcinomas. Both antibodies are likely to be included in the routine diagnostic
armamentarium of many immunohistochemical laboratories in the near future.
PMID- 10197236
TI - Mesenchymal tumors of the gastrointestinal tract: a paradise for acronyms (STUMP,
GIST, GANT, and now GIPACT), implication of c-kit in genesis, and yet another of
the many emerging roles of the interstitial cell of Cajal in the pathogenesis of
gastrointestinal diseases?
AB - This commentary addresses the nature of interstitial cells of Cajal (which can
now be conveniently demonstrated by immunostaining for c-kit) and their possible
role in the genesis of various motility disorders of the gastrointestinal tract.
The evolution of the concept on the nature of gastrointestinal stromal tumors is
discussed, with emphasis on the recent finding of a very high frequency of c-kit
immunoreactivity in these tumors, suggesting that they might exhibit
differentiation toward interstitial cells of Cajal. The practical
immunohistochemical applications of antibodies to c-kit in diagnostic pathology
are also discussed.
PMID- 10197237
TI - Benign mesothelial cells in lymph node.
AB - This commentary summarizes the clinicopathologic features of the reported and
personally observed cases of benign mesothelial cells in lymph node. This
condition occurs most commonly in the setting of chronic effusion, serosal
inflammation, or reaction to adjacent lymphoma. The differential diagnosis from
metastatic mesothelioma is discussed.
PMID- 10197238
TI - Micronodular pneumocyte hyperplasia: the versatile type 2 pneumocyte all dressed
up in yet another brand new suit!
AB - This commentary discusses the variety of nonneoplastic proliferations, putative
preneoplastic lesions, and benign neoplasms of type 2 pneumocytes; the nature and
differential diagnosis of micronodular pneumocyte hyperplasia; and the pulmonary
manifestations of tuberous sclerosis complex.
PMID- 10197239
TI - Convergent strabismus in a white Bengal tiger.
AB - A white Bengal tiger was noted to have a convergent strabismus with poor vision
since a cub. The tiger and a littermate with normal colouring and apparently
normal eyes were anaesthetised for comparative ocular examination. A fundus
typical of colour-dilute cats and dogs was noted in the white tiger. Except for
strabismus, no abnormalities were observed. Electroretinography showed similar
retinal function in both tigers. Possible causes of strabismus considered were an
adaptation to genetically determined abnormal visual pathways related to lack of
pigment, abnormalities of the abducent nerves and mechanical restricting
conditions of the medial rectus muscles.
PMID- 10197240
TI - Hansen type I disk disease at T1-2 in a dachshund.
AB - A 7-year-old Dachshund was presented with chronic left thoracic limb lameness and
acute neurological deficits to the hind limbs following trauma. A lesion was
suspected between C7 and T2 on the basis of neurological examinations.
Radiography and myelography identified a calcified intervertebral disk at C7-T1
and an extradural unilateral compressive lesion at T1-2. Computed tomography
scans of the cranial thoracic spine revealed extrusion of disk material from the
T1-2 intervertebral space resulting in marked spinal cord compression.
Intervertebral disk disease is rarely reported at this location. The neurological
condition deteriorated after a second myelogram, which was done to examine the
thoracolumbar spine. A modified dorsal decompression of T1-2 was performed. The
dog was euthanased due to further neurological deterioration 8 days after
surgery.
PMID- 10197241
TI - Haematuria in a geriatric cat.
PMID- 10197242
TI - Surgical treatment of gastric leiomyoma in a dog.
AB - A 12-year-old entire male Maltese terrier was presented with a 1 month history of
vomiting and haematemesis. Microcytic hypochromic anaemia was detected. Abdominal
radiography, ultrasonography and gastric endoscopy identified a discrete
intramural mass in the pyloric antrum. An ulcerated leiomyoma was removed by a
partial-thickness intraluminal resection of the gastric wall. The dog recovered
well and is free from clinical signs 20 months after surgery.
PMID- 10197243
TI - Full-thickness resection of the hard palate for treatment of osteosarcoma in a
dog.
PMID- 10197244
TI - Partial phallectomy to treat priapism in a horse.
PMID- 10197245
TI - Multi-resistant Salmonella Typhimurium DT104--implications for animal industries
and the veterinary profession.
PMID- 10197246
TI - Content and distribution of macro- and micro-elements in the body of pasture-fed
young horses.
AB - OBJECTIVE: To determine the content and distribution of Na, K, Ca, P, Mg, S, Cu,
Mn, Fe and Zn in the body of pasture-fed young horses and then use a factorial
model to calculate the dietary mineral requirements for growth. PROCEDURE: Twenty
one foals were killed at about 150 days of age and the organs, soft tissues, skin
and bones and a sample of muscle were dissected out and weighted. The mineral
concentrations of elements in all soft tissues and bones were measured by
inductively coupled emission spectrometry. The total mineral element composition
associated with a tissue was determined from the weight of tissue and its mineral
element concentration. RESULTS: Expressed as a percent of total body mineral
elements, muscle contained 20% Na, 78% K, 32% Mg, 62% Cu, 36% Mn and 57% Zn, bone
contained 47% Na, 99% Ca, 81% P, 62% Mg, 30% Mn and 28% Zn while the organs
accounted for a smaller percentage ranging from 0.06% for Ca to 26% for Fe. In
liver Cu accounted for 9.2% of total body Cu. Each kilogram of empty body weight
was associated with 1.0 g Na, 2.5 g K, 17.1 g Ca, 10.1 g P, 0.4 g Mg, 1.1 mg Cu,
0.39 mg Mn, 52.5 mg Fe and 21.4 mg Zn. CONCLUSION: The mineral element content of
body weight gain is a component used in the factorial model to determine dietary
mineral element requirements for growth. The calculated dietary mineral
requirements, expressed per kg dry matter, for a 200 kg horse gaining 1.0 kg/day
were 1.0 g Na, 2.1 g K, 4.6 g Ca, 3.5 g P, 0.7 g Mg, 4.5 mg Cu and 25 mg Zn.
PMID- 10197247
TI - Concentrations of macro- and micro-elements in the milk of pasture-fed
thoroughbred mares.
AB - OBJECTIVE: To determine the changes in Ca, P, Mg, Na, K, S, Cu, Fe and Zn
concentrations of milk during the lactation in pasture-fed Thoroughbred mares and
then calculate the dietary mineral requirements of the sucking foal and the
lactating mare. PROCEDURE: Milk was sampled on days 1, 3, 7, 14, 21, 28 and at
various times between 55 to 65, 85 to 95 and 135 to 150 days after parturition
from 21 pasture-fed mares. The concentrations of macro- and micro-elements in the
milk were determined by inductively coupled plasma emission spectrometry.
RESULTS: Concentrations (mg/L) of these elements were highest in colostrum (Mg
302, Na 561, K 955, S 1035, Cu 0.76, Fe 0.79 and Zn 5.5) except for Ca (1245) and
P (895), which where highest on day 7. The mean milk mineral element
concentrations (mg/L) over days 55 to 150 were Ca 843, P 543, Mg 47, Na 120, K
590, S 219, Cu 0.19, Fe 0.34 and Zn 2.1. The mean plasma element concentrations
(mg/L) over the same period were Ca 120, P 77.1, Mg 17.0, Na 3110, K 168, S 983,
Cu 1.1, Fe 1.5 and Zn 0.49. Concentration gradients between plasma and milk were
observed and, in the case of Ca, P, Mg, K and Zn, their concentrations in milk
were greater than those in plasma, while a reverse situation was observed for Na,
S, Cu and Fe. CONCLUSION: With the exception of Ca and P, the highest
concentrations of mineral elements were observed in the colostrum. The nursing
foal should have access to good pasture or creep feed, because the intakes of Ca,
P and Cu from milk may be less than optimum to meet the daily mineral element
requirements.
PMID- 10197248
TI - Immobilisation of pinniped species.
PMID- 10197249
TI - Sequence analysis of Australian infectious bursal disease viruses.
PMID- 10197250
TI - Effects of temperature and pH on the osmotic fragility of erythrocytes of yaks.
PMID- 10197251
TI - Postnatal persistence of foetal haemoglobin in yaks.
PMID- 10197252
TI - Adenovirus pneumonia in guinea pigs.
PMID- 10197253
TI - Organophosphorus nomenclature.
PMID- 10197254
TI - Vaccines against bovine babesiosis--longest field trial?
PMID- 10197255
TI - Product warning: FRONTLINE.
PMID- 10197256
TI - Evaluation of the Vega haematology analyser in a university hospital setting.
AB - The performance of the ABX Vega haematology analyser was compared with that of
the Sysmex NE-8000, with specific attention to flagging performance and
ergonomics. Eight hundred routine samples underwent precision and interinstrument
variability studies and 168 samples corresponding to various blood disorders were
studied meanwhile. Results from the two instruments gave excellent correlation (r
> 0.900) for most parameters except MCHC (r = 0.114), basophil and monocyte
percentages (r = 0.617 and 0.552, respectively). The reproducibility,
repeatability, linearity, carry-over and stability of the Vega were satisfactory;
'flagging' occurred in 31% of routine samples with sensitivity 88.8%, specificity
41.3% and positive predictive value 85.7%. Various flags appeared in 91% (42/46)
of cases where blast cells were microscopically identified. In the four remaining
cases, CBC anomalies would themselves have justified microscopic examination of a
smear. On 'CBC only' mode reagent consumption was significantly reduced. In the
laboratory the analyser was best appreciated for its user-friendliness.
PMID- 10197257
TI - Consensus and accuracy in haematology laboratories of developing countries: the
Jordanian experience.
AB - A study lasting for 18 months using interlaboratory surveys was carried out to
assess the analytical quality of Jordanian haematology laboratories that
represent one of the developing countries. The study surveyed 50 laboratories
constituting the majority of clinical laboratories in the central region of
Jordan using 15 control specimens of whole fresh blood and eight freshly prepared
blood smears. The study covered the routine haematological parameters of PCV, Hb,
RBC, WBC and differential white blood cell count. More than 97% of Jordanian
laboratories using cell counters achieved the medically useful criteria for
analytical performance, this figure was reduced to 84% in laboratories using
manual methods. Jordanian laboratories, however, were far from achieving the
analytical goals that have been proposed based on intraindividual biological
variation. This study stressed the need for a national EQA scheme in haematology,
to reach a common level of standardization.
PMID- 10197258
TI - Loss of the Y chromosome in bone marrow cells: results on 1907 consecutive cases
of leukaemia and preleukaemia.
AB - Loss of the Y chromosome with a resulting 45, X0 karyotype is observed in normal
bone marrow cells of elderly males but also in haematological malignancies.
Whether Y loss in neoplastic cells is related to the process seen in normal
ageing or is part of the carcinogenic process is unknown. The present study
concerns the cytogenetic data from 1907 consecutive leukaemic or preleukaemic
male patients with special regard to the presence or absence of the Y chromosome.
Sixty-five patients (3.4%) had a 45, X-Y clone in their bone marrow (BM) cells.
Loss of Y was rare below the age of 50 but increased in older patients, reaching
25% of the men over 80. Sixteen patients (0.08%) had more than 90% X0 cells in
their BM. A correlation between Y loss and leukaemia could be established in
seven cases, three of which were acute myeloid leukaemia M2 subtype where -Y is
known to be a secondary event. In three other cases, -Y was part of a complex
karyotype. Only one patient exhibited a 45, X0 karyotype, with no other
rearrangement, that could be positively correlated with the neoplastic process.
PMID- 10197259
TI - Factors influencing platelet recovery after autologous transplantation of G-CSF
mobilized peripheral blood stem/progenitor cells following myeloablative therapy
in 50 heavily pretreated lymphoma patients.
AB - Delayed platelet recovery following autologous PBPCs transplantation after
myeloablative therapy remains an unresolved problem in lymphoma patients heavily
pretreated with several chemotherapy cycles and/or radiotherapy. In the present
study of 50 lymphoma patients, the factors influencing platelet recovery after
myeloablative therapy followed by autologous PBPCs transplantation were analysed
retrospectively. The median age was 42 years (range, 15-58). Fourteen patients
had HD and 36 had NHL (13 high-grade and 23 low-grade); most (80%) had stage III
or IV. Twenty-two patients had received radiotherapy to various extents before
mobilization. The mean number of previous chemotherapy cycles was seven (range 3
24) of different regimens (range 1-4). A median of three leukapheresis procedures
(range 1-5) was performed after G-CSF mobilization. Single leukapheresis was
sufficient in only one patient. A significant correlation was found between the
BFU-E content of autografts and platelet recovery after transplantation. Neither
the patient's age and sex nor the stage and grade of lymphoma had any effect on
platelet recovery after transplantation. Neither the type of myeloablative
therapy used or the dose of G-CSF administered after transplantation had any
effect on platelet recovery after transplantation. The type of previous
chemotherapy cycles was a major adverse factor affecting the progenitor cell
yield in the autografts. Lymphoma patients previously treated with ASHAP and/or
Dexa-BEAM cycles had less progenitor cell yield. The chemotherapeutic agents used
in previous cycles also had a clear adverse effect on the progenitor cell yield
in the autografts. Lymphoma patients previously treated with cycles including
cytarabine and/or cisplatin showed significantly less progenitor cell yield and
slower platelet recovery after transplantation. All seven patients with delayed
platelet recovery had received cytarabine and/or cisplatin in several previous
ASHAP and/or Dexa-BEAM cycles. All seven patients had a BFU-E count of less than
1 x 10(5)/kg yield in the autografts.
PMID- 10197260
TI - Relationship between intracellular calcium-dependent process and protein-tyrosine
phosphorylation in human platelets: studies of platelets from a patient with
defective A23187-induced platelet aggregation.
AB - We had postulated that in a patient with defective calcium ionophore (A23187)
induced platelet aggregation, whose platelets showed normal intracellular Ca2+
mobilization in either the presence or absence of extracellular Ca2+ in response
to A23187. A defect was present in an intracellular calcium-dependent process. We
have now investigated whether the agonist-induced protein-tyrosine
phosphorylation (PTP) was altered. Protein-tyrosine phosphorylation (PTP)-induced
by A23187 in the patient's platelets was greatly diminished but that induced by
thrombin was almost normal. These results suggest that an intracellular calcium
dependent process plays a fundamental role in A23187-induced PTP, whereas it does
not in thrombin-induced PTP.
PMID- 10197261
TI - The differential effects of aspirin on platelets, leucocytes and vascular
endothelium in an in vivo model of thrombus formation.
AB - Unanswered questions remain with regard to the therapeutic use of aspirin and the
selective inhibition of thromboxane A2 and prostacyclin in platelets and
endothelial cells. In the present study, the effects of aspirin on platelets and
endothelial cells in vivo were examined using a helium-neon (He-Ne) laser-induced
thrombosis model. Single intravenous injections of aspirin at concentrations of
more than 0.5 mg/kg body weight mediated a dose dependent inhibition of thrombus
formation in arterioles but not in venules. This antithrombotic effect was
optimum after 15 min and declined after 90 min. Potent antithrombotic activity in
arterioles was manifest at doses of 2.5 mg/kg to 50 mg/kg, and initial inhibition
of thrombogenesis in vivo was most pronounced at high doses. Oral aspirin also
inhibited thrombus formation in arterioles but not in venules, although the
antithrombotic effects were delayed and prolonged. Maximum inhibition of ex vivo,
collagen induced platelet aggregation by aspirin was observed approximately 180
min after intravenous injection. The results demonstrated that, although aspirin
might have differential effects on platelets and endothelial cells, potent
antithrombotic activity was manifest in arterioles at all concentrations. The
findings suggest that the concept of the aspirin dilemma might be ignored for
therapeutic purposes in many clinical circumstances. The antithrombotic effects
of aspirin were unchanged in granulocyte-depleted animals, indicating that
leucocyte-related mechanisms including neutrophil superoxide anion production did
not modulate the potency of aspirin in this model.
PMID- 10197262
TI - Helicobacter pylori infection is not a correlate of plasma fibrinogen in the
Australian population.
AB - Plasma fibrinogen concentration is an important independent risk factor for
cardiovascular disease. Studies into whether Helicobacter pylori infection and
fibrinogen are associated have yielded inconsistent results. Despite the
geographical variation in fibrinogen and prevalence of H. pylori infection, all
studies to date have been undertaken in the United Kingdom or Italy. The
association between H. pylori infection and fibrinogen was investigated in 324
adults, 65% of a random sample, in an Australian regional city. The mean plasma
fibrinogen concentration in 98 infected participants (2.52 g/l) was similar to
that in 226 non-infected subjects (2.58 g/l, P = 0.51); 95% confidence interval
on the difference was -0.23-0.11 g/l. After including all potential confounding
factors in a backward multiple linear regression analysis, H. pylori was still
not associated with fibrinogen (P = 0.084). Any association between H. pylori and
cardiovascular disease in Australia is not mediated through fibrinogen.
PMID- 10197263
TI - Ratio of factor V activities in PT and APTT assays as a new diagnostic marker of
lupus anticoagulant.
AB - Lupus anticoagulant (LA) is an antibody that interferes with phospholipid
dependent coagulation tests. We investigated the usefulness of the ratio of
factor V activity determined by the Simplastin auto test (PT assay) to factor V
activity determined by the Platelin Excel LS test (APTT assay) for detection of
LA in plasma samples obtained from 276 patients with haematological and non
haematological disorders and 73 healthy subjects. This ratio was significantly
higher in the 15 LA-positive (4.82 +/- 3.34) than in samples from healthy
subjects (1.09 +/- 0.10) and was > 1.4 in 10 of the remaining 261 patient
samples. The ratio was particularly low in the 54 samples from warfarin-treated
patients. These findings suggest that determination of this ratio may be useful
as a routine laboratory test for detection of LA. This test requires no specific
antigens and can be applied in patients receiving anticoagulants such as warfarin
and heparin.
PMID- 10197264
TI - Abnormal coagulation and deep venous thrombosis in patients with advanced cancer.
AB - Many studies have demonstrated increased coagulation activation in cancer
patients and have shown evidence of chronic, low-grade disseminated intravascular
coagulation, although most patients remained asymptomatic. In general, patients
have not been screened for deep venous thrombosis (DVT). We screened 98 patients
with advanced malignancy for DVT using light reflection rheography. Coagulation
profiles of DVT and non-DVT groups were studied. We found a high prevalence of
DVT (50%) on screening. Overall, the patients had raised levels of fibrinogen
(66% patients), factor VIII:C (43%), fragment 1 + 2 (71%) and TAT levels (89%).
Patients with DVT had a significantly lower level of fibrinogen than those
without (4.0 g/dl, SD 1.4, compared with 4.7 g/dl SD 1.6, P = 0.04). There was no
significant difference in other coagulation or liver function tests between the
DVT and non-DVT groups. The wide variation of results makes their interpretation
difficult and unlikely to be of predictive value in estimating individual
thrombotic risk.
PMID- 10197265
TI - Three different chromogenic methods do not give equivalent anti-Xa levels for
patients on therapeutic low molecular weight heparin (dalteparin) or
unfractionated heparin.
AB - In this study we compare three chromogenic methods (IL-Heparin, Stachrom Heparin
and Heparin Sigma) on two different instruments (ACL300+ and AMAX CS190) for
patients on dalteparin (n = 41), a low molecular weight heparin or unfractionated
heparin (n = 50). For dalteparin the mean anti-Xa levels for IL-Heparin, Stachrom
Heparin and Heparin Sigma were 0.27, 0.30 and 0.21 U/ml, respectively, while for
heparin they were 0.52, 0.55 and 0.41 U/ml, respectively. To test for instrument
specific effects, IL-Heparin and Stachrom Heparin were repeated on both
instruments on 42 patients receiving unfractionated heparin. For IL-Heparin the
mean anti-Xa levels on the AMAX CS190 and ACL300+ were 0.51 and 0.59 U/ml,
respectively, while for Stachrom Heparin they were 0.55 and 0.67 anti-Xa U/ml. We
conclude that different chromogenic anti-Xa methods do not give equivalent anti
Xa levels for the same samples. Moreover, the differences are clinically
significant. This is not explained entirely by instrumentation effects.
Recommended therapeutic ranges may need to be method and instrument specific.
PMID- 10197266
TI - Co-incidental presentation of IgA lambda multiple myeloma and pleural involvement
with IgM kappa non-Hodgkin's lymphoma.
AB - Pleural effusions occur in approximately 6% of patients with myeloma. The
aetiology is multifactorial and effusions due to pleural myelomatous involvement
are rare, occurring in < 1% of cases. We report the case of a 68-year-old lady
who presented with IgA myeloma and a concurrent pleural effusion due to a second
IgM kappa producing B cell neoplasm. The former responded but the latter was
resistant to standard myeloma therapy.
PMID- 10197267
TI - Artefactual elevation of an automated white cell count following femoral vein
puncture.
AB - We report the novel occurrence of an erroneous automated total and differential
white blood cell count on a blood sample obtained by traumatic femoral
venepuncture, caused by contamination of the blood sample with subcutaneous
adipose tissue. The erroneous counts were observed on a Bayer-Technicon H2
analyser while counts on a Coulter GenS, were much less affected. Characteristic
scatter plots from both instruments are illustrated.
PMID- 10197268
TI - Graves' disease following successful treatment of severe aplastic anaemia with
antilymphocyte globulin.
AB - This case report is only the third report of thyroid dysfunction following the
administration of anti-lymphocyte globulin for severe aplastic anaemia. It is the
first report of the development of Grave's disease. We discuss a possible
mechanism by which this may occur and highlight instances of other immune
mediated diseases occurring in ALG treated patients.
PMID- 10197269
TI - Long-term preservation of platelet count in blood for external quality control
surveillance using prostaglandin E1.
PMID- 10197270
TI - Reference intervals for haematological parameters in urban school children and
adolescents.
PMID- 10197271
TI - [Magnetic resonance spectroscopy in sudden deafness. As early as necessary-as
late as possible].
PMID- 10197272
TI - [Otorrhea in myringotomy tubes].
PMID- 10197274
TI - [Guideline "Providing hearing aids" of the German Society for Ear, Nose and
Throat Medicine and Head and Neck Surgery].
PMID- 10197273
TI - [Materials for reconstruction of the middle ear].
AB - To rehabilitate most cases of conductive hearing loss closure of ear drum
perforations and rebuilding of the ossicular chain can be performed. Due to the
great number of biocompatible bone substitute materials available it is
occasionally difficult for the surgeon to choose the most favorable substitute.
Autogenous structures (ossicles, cortical bone, cartilage) and allogenous tissues
(ossicles, cortical bone, cartilage, dentin) are possible bone replacement
materials. Xenogenic tissue is currently not used in middle ear surgery. Ionomer
cement is a hybrid material for replacement of bone but does not fit direct
classification of the various classes of alloplastic materials in current use:
that is, metals (gold, steel wire, platinum, titanium), plastics (polyethylene,
polytetrafluorethylene) and ceramics (ceramic oxide, carbon, calcium-phosphate
ceramic, vitreous ceramic). For restoration of the sound conductive apparatus
preference is given to autogenous ossicles because cortical bone is resorbed and
cartilage weakens over time. Most surgeons do not use allogenous tissue, because
of the possible transmission of such infectious disease as immunodeficiency
syndrome or Creutzfeldt-Jakob disease. Only dentin deserves special attention as
a possible bone substitute in the middle ear because its form can be preserved
during sterilization. Based on the observations available to date, it becomes
apparent that titanium implants hold greater promise than gold. Form-stable
synthetic materials are not generally recommended due to foreign body reactions
which have been confirmed by many investigators. Ceramic materials (e.g. ceramic
oxide, carbon, calcium-phosphate ceramic, glass ceramic) are well tolerated in
the middle ear and have also proved to be useful over time. Hybrid bone
substitute ionomer cement is easily workable and well integrated, showing a good
functional outcome. For many years good results in otosclerosis surgery have been
achieved with a prosthesis made of platinum-wire and Teflon. Short-term follow-up
periods hold great promise with pistons made of gold. Autogenous ossicles,
ionomer cement and recently titanium protheses--as far as usable--are employed by
the author for reconstructing the middle ear. For the time being platinum-Teflon
prostheses and gold are used in otosclerosis surgery.
PMID- 10197275
TI - [Extended indications for cochlear implantation. The Freiburg results in patients
with residual hearing].
AB - The usual indication for a cochlear implant (CI) is acquired deafness in patients
for whom conventional hearing aids are of no benefit. The question is whether CI
is superior to the best conventional hearing aids for patients with some residual
hearing, but who achieve only minimal speech recognition (< 30% in the Freiburg
monosyllable word test at 70 dB (I) SPL) with optimal hearing aids. We report our
experience with five patients with residual hearing who underwent cochlear
implantation (Nucleus Mini 22 and 24) on the worse side. The patients were
examined preoperatively and at 1, 6 and 12 months following activation of the
implant. The Freiburg monosyllabic word test, the Gottingen sentence test and
consonant recognition were used to assess postoperative results. All patients
benefitted from CI when test scores were compared with preoperative ones. All
patients achieved a score in the Freiburg monosyllabic word test of more than 60%
at 70 dB (I) SPL 12 months post switch-on. Four patients achieved a score of more
than 85% in the Gottingen sentence test. These results and the progress made in
cochlear implant technology are an impetus to continue discussions of various
considerations of criteria for cochlear implants and possibly extend these for
patients with severe hearing impairment.
PMID- 10197276
TI - [Controlled cosmetic dermal ablation in the facial region with the erbium:YAG
laser].
AB - The erbium: YAG laser (wavelength 2940 nm; pulse duration 0.350 ms; pulse energy
0.1-1.7 J) allows vaporization of very thin skin layers without scarring and
minimal lateral thermal injury due to an extremely short pulse duration. It
permits exact ablation of relatively large areas of facial skin. We report our
results with 216 patients following treatment for different facial lesions
(facial wrinkles, acne scars, syringomas, and circumscribed sebaceous gland
hyperplasia) using a new erbium: YAG laser system. Good-to-excellent cosmetic
results were obtained in these patients. Our findings show that the erbium: YAG
laser is an elegant and promising new method for the treatment of facial lesions.
PMID- 10197278
TI - [24 hour pH monitoring of the hypopharymx].
AB - Monitoring of pH of the esophagus is a routine diagnostic procedure, whereas
until now pH-monitoring of the hypopharynx has been used only for scientific
research. In the present study a critical evaluation scale was used to record the
results of 112 patients who underwent pH monitoring to determine possible reflux.
Since high refluxes often remain unnoticed clinically, further study is required
in certain cases. The extent of reflux in the esophagus may not represent
pathological changes in the hypopharynx. In such cases 24-h pH monitoring of the
hypopharynx can be a useful diagnostic procedure and may also help detect the
pathogenesis of "gastric laryngitis".
PMID- 10197277
TI - [Infection frequency and type of bacteria after tympanostomy tube drainage in
childhood: gilded-silver tubes versus silicone tubes].
AB - Otorrhea is the most common complication after tympanostomy tube insertions. In
Germany there are currently two commonly used types of tympanostomy tubes:
silicon tubes (ST) and gilded silver tubes (GT). Previously published in vitro
studies by Tajima uncovered a positive correlation between the silicon
concentration in culture fluid and the rate of growth of Staphylococcus aureus.
Our study retrospectively evaluates the types of bacteria and rates of otorrhea
after ST and GT insertions. The present study was undertaken to determine which
of these tubes had a higher incidence of otorrhea and then whether silicon tubes
stimulated the growth of certain types of bacteria, such as Staphylococcus
aureus. In all, 186 ST and 59 GT were placed in 245 ears of 144 children. Both ST
and GT were separated into three groups: first insertion of a tympanostomy tube,
second implantation and insertion of a tympanostomy tube in an infected ear in
the course of a mastoidectomy. No differences between ST and GT in causing
otorrhea were found in the three groups. Nevertheless, ST in comparison to GT was
associated with a higher incidence of infections with Pseudomonas aeruginosa. In
contrast, a higher incidence of Staphylococcus aureus related to ST could not be
proved. Twenty percent of the ears with mastoiditis were found to have
Pseudomonas aeruginosa, but none of these ears implanted with a GT developed
postoperative otorrhea. Our findings show that GT should be used when a
ventilation tube is used during a mastoidectomy. Further, it is tenable to
implant only GT because postoperative otorrhea in many cases is caused by
insufficient water protection and water is frequently polluted with Pseudomonas
aeruginosa.
PMID- 10197279
TI - [Sleep apnea syndromes in multiple system atrophy].
AB - Multiple-system atrophy (MSA) is characterized by progressive autonomic failure
with cerebellar, pyramidal and extrapyramidal signs. In MSA patients laryngoscopy
often reveals unilateral or bilateral abductor vocal fold palsies. Snoring is
very common. However, assessment of sites of obstruction and their severity is
needed. We report our clinical experience in managing a 56-year-old, obese male
MSA patient (1.76 m height, 100 kg weight, BMI 32.3 kg/m2) who was admitted for
evaluation of snoring and excessive daytime sleepiness. Endoscopy while awake
demonstrated an incomplete abductor vocal fold palsy. Polysomnography confirmed
heavy snoring with arousals (11.1/h) and an RDI of 1.4/h. Sleep efficiency was
low (51.9%) due to long intermittent awake periods. Sleep videoendoscopy of the
upper airway proved the entire pharynx to be open during REM and non-REM sleep.
During inspiration fluttering movements of the vocal cords caused the snoring.
This was regularly terminated by arousals. The further treatment is discussed. In
general, glottic snoring without daytime stridor is rare and has only been
described in MSA patients. However, certain of these patients will also be
pharyngeal snorers. The source of the sound and site of obstruction can only be
diagnosed by sleep videoendoscopy.
PMID- 10197280
TI - [Glomus tumor of the nose].
AB - Between May 1995 and March 1996 we were able to diagnose and remove glomus tumors
of the left nasal cavity from three female patients. Ages of the patients were 9,
36 and 74 years. All patients suffered from a frequent epistaxis and all were
extremely sensitive to the slightest nasal touch. One patient reported breathing
difficulties due to nasal congestion. Examination revealed a tumor that filled
the entire nasal cavity. The method of choice in treatment of these tumors is
surgical removal. Hemangiopericytoma, non-chromaffin paraganglioma, hidradenoma,
cavernous hemangioma and nevus cell nevi have to be excluded by histology and
immunohistochemical techniques. From a clinical perspective the bleeding septal
polyp (granuloma telangiectaticum sive pyogenicum sive pediculatum) has to be
considered because it often comes from Kieselbachi's plexus, has a mushroom-like
appearance and bleeds slightly.
PMID- 10197281
TI - [Unilateral nasal breathing difficulties].
PMID- 10197282
TI - [Metal thread hanging from the mouth].
PMID- 10197283
TI - [Psychological principles in the treatment of tinnitus patients].
PMID- 10197286
TI - Periodontal disease and risk of fatal coronary heart and cerebrovascular
diseases.
AB - BACKGROUND: Recent reports have implicated periodontal disease as a risk factor
for coronary heart disease (CHD). METHODS: A retrospective cohort study was
conducted using participants in the 1970-1972 Nutrition Canada Survey (NCS). The
mortality experience of male and female NCS participants aged 35-84 years without
self-reported CHD (n = 10,368) or cerebrovascular disease (CVD) (n = 11,251) was
determined through 1993. The relation between dental health and the risk of fatal
CHD and CVD was assessed using Poisson regression modeling. RESULTS: In total,
466 CHD and 210 CVD deaths were observed; missing confounder data reduced these
numbers to 416 CHD and 182 CVD deaths. Adjusted for age, sex, diabetes status,
serum total cholesterol, smoking, hypertensive status, and province, we found a
statistically significant association between periodontal disease and risk of
fatal CHD. Rate ratios (RR) of 2.15 [95% confidence interval (CI) 1.25-3.72) and
1.90 (95% CI 1.17-3.10) were observed for severe gingivitis and edentulous
status, respectively. Non-statistically significantly increased RRs of 1.81 and
1.63 were observed for severe gingivitis and edentulous status for CVD.
CONCLUSIONS: These data indicate that poor dental health is associated with an
increased risk of fatal CHD.
PMID- 10197285
TI - Lipoprotein (a) and apolipoprotein E epsilon 4 as independent risk factors for
ischemic stroke.
AB - BACKGROUND: Controversies exist concerning the association between serum lipids
and ischemic stroke. OBJECTIVE: To investigate the relationship between serum
lipid, apolipoprotein E (apoE) genotype and risk of ischemic stroke. METHODS: We
measured the concentrations of serum lipids, lipoprotein (a) [Lp(a)], and apoE
genotype, as well as the distribution of other potential risk factors, in 90
pairs of age- and sex-matched ischemic stroke patients and stroke-free controls.
RESULTS: The prevalence of hypertension, family history of stroke and
hypertension, and smoking and drinking habits were significantly higher in cases
than in controls. Total cholesterol, low-density lipoprotein cholesterol, and
Lp(a) levels were higher in ischemic stroke patients than in controls (5.7 +/-
1.2 versus 5.3 +/- 1.2 mmol/l, P < 0.05; 3.7 +/- 1.0 versus 3.1 +/- 1.0 mmol/l, P
< 0.01; and 197.6 +/- 30.6 versus 90.4 +/- 11.2 mg/l, P < 0.01, respectively).
The cases had lower high-density lipoprotein cholesterol and apolipoprotein A-1
concentrations compared with the controls. The apoE epsilon 3/epsilon 4 genotype
was more frequent in cases (21.1%) than in controls (8.9%, P < 0.05). CONCLUSION:
The results of the study indicate that serum Lp(a) level and apoE epsilon 4 are
the prominent lipidic predictors for ischemic stroke in addition to the general
risk factors such as history of hypertension, family history of stroke and
cigarette smoking.
PMID- 10197287
TI - Genetic polymorphism of platelet glycoprotein IIIa in patients with acute
myocardial infarction and acute ischaemic stroke.
AB - BACKGROUND: It has recently been suggested that the Leu33Pro polymorphism of the
platelet glycoprotein IIIa affects the risk of coronary thrombosis. Finland is
genetically isolated and has an incidence of cardiovascular disease among the
highest in the world. Interestingly, the prevalence of ischaemic heart disease
also varies in different parts of the country, being highest in eastern Finland.
METHOD: We studied the Leu33Pro polymorphism using polymerase chain reaction in
133 patients with coronary artery disease, 234 patients with cerebrovascular
disease and 326 control subjects originating from two areas of Finland. RESULTS:
The frequencies of the Pro33 allele in the patients with acute myocardial
infarction and cerebrovascular attack were 13% and 14%, respectively, and did not
differ from the controls (13%). Among patients with acute myocardial infarction
from the Helsinki area, the family history of premature coronary artery disease
was more often positive in carriers of the Pro33 allele than in non-carriers, but
after adjustment for multiple comparisons the difference was no longer
significant. CONCLUSIONS: We could not confirm the original observation that the
Pro33 allele constitutes an independent risk factor for coronary artery disease.
Further studies are needed to clarify whether co-occurrence of Pro33 and some
unrecognized inherited factor pose an additional risk of vascular disease.
PMID- 10197289
TI - The prognostic importance of smoking status at the time of acute myocardial
infarction in 6676 patients. TRACE Study Group.
AB - Smoking is an important risk factor for atherosclerotic heart disease, but
several studies have shown smoking to be associated with a favourable prognosis
in patients who have suffered an acute myocardial infarction (AMI). We studied a
large group of consecutive patients admitted alive to hospital with an infarction
in order to further study the prognostic importance of smoking status at the time
of myocardial infarction. The study cohort comprised 6676 patients with an enzyme
confirmed myocardial infarction admitted to 27 Danish hospitals over a 26-month
period between 1990 and 1992. Smoking status was determined at the time of
hospitalisation and complete follow-up was obtained in October 1996. Smokers were
on average 10 years younger, had fewer concomitant cardiac risk factors, and were
more likely to be male and to receive thrombolytic therapy more frequently than
non-smokers. In univariate analysis, smoking was associated with reduced 30-day
and long-term mortality (risk ratio at 30 days 0.55, P < 0.001, risk ratio long
term 0.59, P < 0.001). When age only was included in a multivariate analysis,
smoking was no longer of importance in short- or long-term mortality (risk ratio
0.92, P = 0.4 at 30 days and long-term risk ratio 0.98, P = 0.7). Inclusion of
further variables did not change this picture. In conclusion, smoking contributes
to the occurrence of AMI at a younger age. The more favourable prognosis in
smokers at the time of AMI is a result of more favourable baseline
characteristics, especially their lower age.
PMID- 10197290
TI - Therapeutic angiogenesis: protein and gene therapy delivery strategies.
AB - Angioplasty and surgical bypass, the primary interventional therapies for the
treatment of atherosclerosis, are limited by the development over time of native
vessel restenoses and graft occlusions. Furthermore, these therapies are not
options for a significant number of individuals in whom the extent of vascular
pathology is especially severe or widespread. Angiogenesis, the growth of new
vasculature, is a critical biological response to ischemia that provides
collateralization, or 'biological revascularization' of vascular obstructions.
Therapeutic angiogenesis is a strategy whereby one of several known 'angiogens',
mediators that induce angiogenesis, can be administered to augment the native
angiogenic processes and enhance the formation of collateral vasculature. This
report describes the techniques available for providing therapeutic angiogenesis,
including acute and sustained-release techniques to deliver protein angiogens and
a number of gene therapy strategies to deliver genes coding for the angiogens.
PMID- 10197288
TI - Does nibbling or grazing protect the peripheral arteries from atherosclerosis?
AB - BACKGROUND: It has been suggested that frequent food intake is metabolically
advantageous. We investigated whether meal frequency was associated with the
development of peripheral arterial disease among smokers. DESIGN: Hospital-based
case-control study of smokers, recruited from outpatient clinics and inpatient
wards at two London teaching hospitals. METHODS: Two-hundred and ninety-one
smokers, newly referred with peripheral arterial disease (cases) and 828 age- and
sex-matched smokers without smoking-related disorders and with negative Rose
questionnaire responses for intermittent claudication (controls) were recruited.
All cases and controls completed a validated questionnaire concerning dietary
habits. Odds ratios for peripheral arterial disease in association with several
dietary variables were calculated, after adjustment for confounding variables.
RESULTS: After adjustment for age, sex, pack-years of smoking, diabetes,
hypertension and body mass index, the odds ratio for peripheral arterial disease
among those smokers eating between meals (grazing) compared with those who did
not, was 0.54 (95% confidence interval 0.42-0.83; P < 0.001). Among cases and
controls, grazing was also associated with significantly lower plasma cholesterol
concentrations (median 5.67 mmol/l in grazers compared with 6.08 mmol/l in non
grazers; P < 0.001) in those with apparently similar overall fat intakes. Neither
plasma lipoprotein (a) nor fibrinogen concentrations varied with meal frequency.
CONCLUSIONS: In smokers, grazing was associated with a reduced risk of developing
symptomatic peripheral atherosclerosis. This is the first study to demonstrate
the apparent benefits of grazing on a cardiovascular end-point.
PMID- 10197291
TI - Bibliography current world literature.
PMID- 10197292
TI - DHEA and DHEA-S: a review.
AB - Dehydroepiandrosterone (DHEA) and its sulfated metabolite DHEA-S are endogenous
hormones secreted by the adrenal cortex in response to adrenocorticotrophin
(ACTH). Much has been published regarding potential effects on various systems.
Despite the identification of DHEA and DHEA-S more than 50 years ago, there is
still considerable controversy as to their biological significance. This article
reviews the metabolism and physiology of DHEA and DHEA-S, the influence of age
and gender on concentrations, and changes in endogenous concentrations associated
with disease states and other factors, including diet and exercise. This article
is unique in that it also summarizes the influence of drugs on DHEA and DHEA-S
concentrations, as well as concentrations of DHEA and DHEA-S observed after the
administration of DHEA by various routes. Sections of the article specifically
address DHEA and DHEA-S concentrations as they relate to stress, central nervous
system function and psychiatric disorders, insulin sensitivity, immunological
function, and cardiovascular disorders.
PMID- 10197293
TI - Assessment of QTc prolongation for non-cardiac-related drugs from a drug
development perspective.
AB - It is increasingly likely that non-cardiac-related drugs will need to be
routinely analyzed for their ability to prolong cardiac repolarization. This
leads to potential problems for drug companies in general and statisticians in
particular. A number of issues immediately arise in regard to answering the
question, "Does drug X prolong cardiac repolarization?" These include identifying
what is the desired outcome, what is the dependent variable, and what analysis
method should be used. The purpose of this article is bring to to light some of
the issues regarding the analysis of QTc data, the advantages and disadvantages
of these analysis methods, and some general recommendations.
PMID- 10197294
TI - Altered clearance of theophylline in children with Down syndrome: a case series.
AB - Down syndrome (DS) is a common cause of mental retardation resulting from trisomy
21. Previous reports have described altered pharmacokinetics and pharmacodynamics
in patients with DS. The authors report six cases of infants (2-19 months) with
DS who demonstrated altered theophylline pharmacokinetics. Clearance was
prolonged in most of these patients. No overt toxicity to theophylline was noted
in any of the cases. The authors propose that patients with DS are at increased
risk for altered theophylline pharmacokinetics. The etiology for altered
pharmacokinetics of theophylline may be due to the interface between normal
developmental changes and pharmacogenetic differences associated with DS and/or
the secondary disease states and concomitant drug therapy.
PMID- 10197295
TI - Salivary clearance and urinary metabolic pattern of caffeine in healthy children
and in pediatric patients with hepatocellular diseases.
AB - Measurement of salivary clearance and urinary metabolites of caffeine is an
excellent noninvasive tool for assessing liver function, particularly the
activity of cytochrome P4501A2 (CYP1A2), N-acetyltransferase (NAT), and xanthine
oxidase (XO). This study was undertaken to measure the clearance of caffeine
using saliva as a biological fluid and to assess the activities of the above
mentioned enzymes in healthy children and pediatric patients with liver diseases
using urinary molar ratios of different caffeine metabolites. The well
established two-sample saliva approach was used to measure the clearance of
caffeine in nine pediatric patients with liver diseases (LD) and in nine healthy
children. The caffeine metabolites were also measured in the urine of these
subjects by high-performance liquid chromatography, and urinary molar ratios of 5
acetylamino-6-formylamino-3-methyluracil (AFMU), 1-methylxanthine (1X), 1
methyluric acid (1U), and 1,7-dimethyluric acid (17U) were employed to estimate
the activities of CYP1A2, NAT, and XO. The caffeine salivary clearance and the
percentage of the dose excreted in the form of various metabolites were
significantly (p < 0.035) smaller in the LD patients than those in healthy
children. The urinary molar ratio of [AFMU + 1U + 1X]/17U, which reflects the
activity of CYP1A2, was also significantly (p < 0.0005) reduced in these
patients. However, there were no significant differences between the two groups
in the ratios of AFMU/1X and 1U/1X, which estimate the activities of NAT and XO,
respectively. In conclusion, the data obtained suggest that liver disease in
pediatric subjects significantly reduces the salivary clearance of caffeine and
the activity of cytochrome P4501A2, but it has no impact on the activities of NAT
and XO.
PMID- 10197296
TI - Population pharmacokinetics of lamotrigine adjunctive therapy in adults with
epilepsy.
AB - Plasma concentrations of lamotrigine, an antiepileptic drug obtained in three
adult controlled clinical trials conducted in the United States were pooled and
analyzed using NONMEM, a population pharmacokinetic computer program, to
facilitate development of dosing guidelines. A total of 2,407 lamotrigine plasma
concentrations from 527 patients with epilepsy were analyzed. Regression
equations for oral clearance were developed as a function of body size, age (18
64 years), gender, race, and use of concomitant antiepileptic drugs. The
population mean apparent oral clearance of lamotrigine in adult patients
receiving one concomitant enzyme-inducing antiepileptic drug and not valproic
acid was estimated to be 1 mL/min/kg. Gender and age did not affect clearance
significantly. On average, clearance was reduced by 25% in non-whites and
increased by 13% in patients receiving more than one concomitant enzyme-inducing
antiepileptic agent. Lamotrigine did not influence the disposition of phenytoin
or carbamazepine. Dosing adjustments for lamotrigine in patients receiving
concomitant enzyme-inducing antiepileptic drugs and not valproic acid should not
be necessary for age, gender, or the number of concomitant enzyme-inducing
antiepileptic drugs. Lamotrigine does not influence the dosing requirements for
phenytoin or carbamazepine.
PMID- 10197297
TI - Pharmacokinetics of intravenous alendronate.
AB - Alendronate is a potent bisphosphonate that has been studied for the treatment of
osteoporosis and Paget's disease of the bone. To examine the pharmacokinetics of
this drug, several groups of postmenopausal women were dosed intravenously in
several studies. Twelve patients with metastatic bone disease were administered
an intravenous dose of 10 mg of 14C-labeled alendronate (approximately 26 muCi),
and plasma, feces, and urine samples were collected for 72 hours. Radioactivity
was excreted almost exclusively in urine, and all of it was accounted for by
alendronate. Overall recovery accounted for 47% of dose, with the remainder
presumed to be retained in bone. Metabolism of alendronate was not observed.
Renal clearance of alendronate was 71 mL/min. An additional 10 subjects were
given repeated i.v. administrations of alendronate to demonstrate that previous
exposure does not alter the pharmacokinetic behavior of the drug. Examination of
the findings from these and other studies in which alendronate was administered
intravenously revealed that disposition of single doses is linear in the range of
0.125 to 10 mg. With the possible exception of a somewhat greater skeletal
retention of a systemically administered dose, the pharmacokinetics of i.v.
alendronate were found to be similar to those of other bisphosphonates.
PMID- 10197298
TI - Pharmacokinetics of cisplatin administered by continuous hyperthermic peritoneal
perfusion (CHPP) to patients with peritoneal carcinomatosis.
AB - The pharmacokinetics of cisplatin administered by continuous hyperthermic
peritoneal perfusion (CHPP) was characterized in patients with peritoneal
carcinomatosis. Cisplatin was added into the perfusate with escalating doses from
100 mg/m2 to 400 mg/m2. The hyperthermic perfusion was maintained for 90 minutes
with a flow rate of 1.5 L/min and a target peritoneal temperature of 42.5 degrees
C after a tumor debulking procedure. Samples of both the perfusate and blood were
obtained during the perfusion and 30 minutes after the perfusion. Cisplatin
plasma and perfusate concentrations were determined by flameless atomic
absorption spectrometry with a lower limit of detection of 2 ng/ml and a
coefficient of variation (CV) < 10%. Fifty-six patients were enrolled in the
study. The mean (+/- SD) percentage of cisplatin present in the perfusate at the
completion of perfusion was 27.8% +/- 20% of the total dose. The maximum
cisplatin concentrations in the perfusate were 10 times higher than those in
plasma. The area under the concentration-time curve (AUC) of the perfusate was 13
times higher than the AUC of plasma. A two-compartment model with an additional
peritoneal cavity compartment fits to the data best based on the Akaike
information criterion. However, the interpatient variability was considerably
high (CV < 100%). In conclusion, cisplatin administered by hyperthermic
peritoneal perfusion resulted in a pharmacological advantage by obtaining higher
and direct drug exposure to the tumor in the peritoneal cavity while limiting
systemic absorption and toxicity. Using a complex two-compartment model, the
authors were able to characterize the pharmacokinetics of cisplatin given
intraperitoneally via this technique.
PMID- 10197299
TI - Electronic monitoring of compliance to lipid-lowering therapy in clinical
practice.
AB - Nonadherence to treatment is a common problem in the clinical management of
hypercholesterolemic patients. This study was carried out with the aim of
monitoring the daily compliance to a 6-month course of lipid-lowering therapy,
using a microelectronic device, the Medication Event Monitoring System (MEMS),
versus pill count. Forty men with primary hypercholesterolemia were prescribed
fluvastatin 1 x 40 mg daily, provided in a MEMS package to record the date and
time of each opening of the pillbox. Thirty-nine of 40 patients (98%) completed
the study. Total cholesterol and LDL cholesterol levels decreased significantly
(18% and 25%, p < 0.001) during the 6-month therapy period. A high mean rate of
compliance was achieved by MEMS using the following three indexes--compliance to
total prescribed dose (88.8% +/- 13.5%), compliance to prescribed days (82.4% +/-
19.5%), and compliance to prescribed time of day (81.86% +/- 19.5%)--and by pill
count (93.4% +/- 9.5%). In addition, the MEMS provided some patterns of
nonadherence to medication, undetectable by pill count alone, such as a drug
holiday in 38% of cases, a drug omission for more than 7 consecutive days in 9%
of cases, and, conversely, use of more than the one prescribed daily dose in 47%
of cases. A significant correlation between the rate of compliance and the
decrease in LDL cholesterol was observed only when the compliance was assessed by
MEMS. The results indicate that MEMS is a useful tool for monitoring compliance
in clinical practice and may possibly increase adherence to long-term lipid
lowering therapy.
PMID- 10197300
TI - Effect of troglitazone on the pharmacokinetics of an oral contraceptive agent.
AB - Fifteen healthy women participated in a study to determine the effect of multiple
doses of troglitazone on the pharmacokinetics of Ortho-Novum 1/35 (35 micrograms
ethinyl estradiol [EE] and 1 mg norethindrone [NE]). Participants received three
cycles (21 days each of active drug followed by 7 days without medication) of
Ortho-Novum. During the third cycle, participants also received troglitazone 600
mg qd for 22 days. Pharmacokinetic profiles of EE and NE were determined on day
21 of the second and third cycles. Progesterone and sex hormone binding globulin
(SHBG) levels were also measured. Troglitazone decreased EE Cmax and AUC(0-24) by
32% and 29%, respectively. Likewise, troglitazone decreased NE Cmax and AUC(0-24)
by 31% and 30%, respectively. Plasma SHBG concentrations increased from 113
nmol/L during cycle 2 to 220 nmol/L during cycle 3. Troglitazone reduced plasma
unbound AUC for NE by 49%. Serum progesterone levels were lower than 1.5 ng/mL on
all occasions. Thus, coadministration of troglitazone and Ortho-Novum decreases
the systemic exposure to EE and NE. A higher dose of oral contraceptive or an
alternate method of contraception should be considered for patients treated with
troglitazone.
PMID- 10197301
TI - The effects of fluvastatin, a CYP2C9 inhibitor, on losartan pharmacokinetics in
healthy volunteers.
AB - Losartan is an angiotensin II receptor antagonist that is metabolized by CYP2C9
and CYP3A4 to a more potent antihypertensive metabolite, E3174. Interaction
studies with inhibitors of CYP3A4 have not demonstrated significant changes in
the pharmacokinetics of losartan or E3174. The authors assessed the steady-state
pharmacokinetics of losartan and E3174 when administered alone and concomitantly
with fluvastatin, a specific CYP2C9 inhibitor. A prospective, open-label,
crossover study was conducted in 12 healthy volunteers with losartan alone and in
combination with fluvastatin. The baseline phase was 7 days of losartan (50 mg
QAM), and the inhibition phase was 14 total days of fluvastatin (40 mg QHS), with
the final 7 days including losartan. The authors found that fluvastatin did not
significantly change the steady-state AUC0-24 or half-life of losartan or E3174.
Losartan apparent oral clearance was not affected by fluvastatin. Inhibition of
losartan metabolism appears to require both CYP2C9 and CYP3A4 inhibition.
PMID- 10197302
TI - Urine drug screening.
PMID- 10197303
TI - ABELCET treatment.
PMID- 10197304
TI - Molecular flexibility of retinoic acid under white fluorescent light.
AB - Among the series of metabolic analogs of the eccentric cleavage pathway of beta
carotene with different side chain lengths, retinoic acid was shown to have
exceedingly higher molecular flexibility to undergo photoisomerization into the
geometrical isomers under white fluorescent light. When irradiated with white
fluorescent lamps (1,200 lx), the velocity of photoisomerization of all-trans
retinoic acid (8.4 x 10(-7) mol/L.min) was exceedingly higher than those of the
other analogs: ionylideneacetic acid (4 x 10(-8) mol/L.min), ionylidenecrotonic
acid (3.0 x 10(-7) mol/L.min), all-trans-beta-apo-14'-carotenoic acid (1.7 x 10(
7) mol/L.min), all-trans-beta-apo-12'-carotenoic acid (1.3 x 10(-7) mol/L.min),
and all-trans-beta-apo-8'-carotenoic acid (0.1 x 10(-7) mol/L.min). beta-Carotene
did not undergo photoisomerization under the experimental conditions. The
molecular flexibility of retinoic acid is assumed to be an important basis of the
mechanism of action of retinoic acid.
PMID- 10197305
TI - The large intestine compensates for insufficient calcium absorption in the small
intestine in rats.
AB - We previously demonstrated that the large intestine compensated for decreased
calcium (Ca) absorption caused by renal failure in rats fed a highly fermentable
dietary fiber. In this study, we examined whether the large intestine compensated
for insufficient Ca absorption in the rat small intestine without ingestion of a
fermentable dietary fiber. Rats were fed one of four test diets containing either
insoluble (carbonate) or soluble (gluconate, lactate, or citrate) Ca sources. The
dietary Ca level was 2.0 g/kg, which is lower than the minimum requirement for
rats (3.0 g/kg), to conduct the present study under a condition in which rats can
maximally absorb Ca. To prevent Ca absorption in the small intestine, we replaced
a primary phosphate (KH2PO4) with secondary phosphates (K2HPO4 and Na2HPO4) in
diets. The apparent Ca absorption in the small intestine was estimated by adding
chromic oxide (Cr2O3) as an insoluble and an unabsorbed marker to test diets and
by measuring the ratio of Ca:Cr in the cecal content. The apparent Ca absorption
in the whole intestine was estimated by the intake and fecal excretion of Ca. The
apparent Ca absorption in the small intestine was significantly lower from the Ca
carbonate diet than from the Ca gluconate, lactate, or citrate diets. The
apparent Ca absorption in the whole intestine was not significantly different
among the four groups, and the values were similar to the absorption rates in the
small intestines of rats fed diets containing soluble Ca sources. These results
show the following: (a) In rats fed 0.2% Ca diets containing soluble Ca salts, Ca
is mostly absorbed in the small intestine, even in secondary phosphate intakes;
(b) In contrast, in rats fed a 0.2% Ca diet containing an insoluble Ca salt
(carbonate), Ca is not sufficiently absorbed in the small intestine. However, the
large intestine compensates for the small intestinal Ca absorption decreased by
dietary secondary phosphates.
PMID- 10197306
TI - Fatty acid composition and arachidonate metabolites in the livers of ethanol
treated rats fed an arachidonate-supplemented diet: effect of dietary fat.
AB - The effects of 1% arachidonic acid ethyl ester (AA) administration on the liver
prostanoid metabolites and on serum and liver lipids in 3 g/kg ethanol
administered rats fed 10% lard or corn oil were studied. The rats were divided
into 6 groups: lard-sucrose (Lard-Suc); lard-ethanol without AA (Lard-Et); lard
ethanol with AA (Lard-EtAA); corn oil-sucrose (Corn-Suc); corn oil-ethanol
without AA (Corn-Et); and corn oil-ethanol with AA (Corn-EtAA). Liver
triglyceride increased in Corn-EtAA compared with Corn-Et. Arachidonic acid (20:
4n-6) levels in liver phospholipid were significantly decreased in Corn-Et, but
elevated in Lard-Et. The levels of 20:4n-6 were significantly increased with AA
administration in both ethanol groups. Liver 6-keto-prostaglandin F1 alpha (6
keto-PGF1 alpha) in Corn-Suc (24.7 +/- 5.1 pg/mg protein) was markedly higher
than in Lard-Suc (4.5 +/- 1.2 pg/mg protein), and the 6-keto-PGF1 alpha lowered
significantly with the addition of ethanol (9.3 +/- 0.9 pg/mg protein), but it
increased with AA administration (21.6 +/- 4.9 pg/mg protein). In Lard-EtAA, a
significant increase in 6-keto-PGF1 alpha was observed compared with Lard-Suc.
The liver leukotriene B4 (LTB4) level in Lard-Suc was significantly lower than
that of Corn-Suc. In the corn oil group, ethanol feeding was associated with a
significant increase in liver LTB4. AA administration to Corn-Et suppressed the
elevated LTB4. Serum thiobarbituric acid-reactive substance (TBARS)
concentrations in the corn oil group were higher than in the lard group, and
these concentrations were not altered by AA administration. From these results,
we concluded that the administration of AA in rats treated with ethanol increased
20:4n-6 in liver phospholipid and liver PGI2 levels, irrespective of dietary fat,
and may protect against alcoholic liver injury. AA with a diet rich in linoleic
acid (18:2n-6), however, may increase fat in the alcoholic liver.
PMID- 10197307
TI - Food habits and anthropometric measurements in a group of independent and
institutionalized elderly people in Spain.
AB - Because of an increase in the number of elderly and the problems of nutrition
associated with them, we considered it of interest to study the eating habits of
352 elderly persons (134 males and 218 females) 65 to 95 years of age in an urban
area in the north of Spain (Oviedo). The purpose of this study was specifically
to describe the differences in the eating habits of elderly institutionalized
persons and those resident at home and to detect the nutritional status of 161
subjects living in institutions and 191 living at home. The weight, height, body
mass index (BMI), and triceps skinfold (PTP) of each were recorded. To determine
the eating habits, a questionnaire measuring the frequency of food consumption
was distributed to the subjects. The mean age of the institutionalized elderly
was greater than those living independently. The mean values of BMI indicated
overweight in all cases, with values around those of obesity in independent
females (BMI = 29.97). The value of PTP was found to be within normal limits, but
a greater percentage of institutionalized subjects showed PTP values of less than
P10 (males, 10.2%; females, 11%). Food habits showed that the consumption of fish
and margarine/oil was greater in institutionalized subjects of both sexes.
Independent males consumed more vegetables; females consumed more milk and
greens. Milk, vegetables, fruit, and fish were the food groups with consumption
frequencies less than those recommended. A greater percentage of noncompliance
was seen among the institutionalized elderly.
PMID- 10197308
TI - Dietary supplementation of catechins and alpha-tocopherol accelerates the healing
of trinitrobenzene sulfonic acid-induced ulcerative colitis in rats.
AB - The effects of dietary catechins and alpha-tocopherol on inflammatory bowel
disease in rats were examined. Male 9-week-old rats were intracolonically
administrated trinitrobenzene sulfonic acid (TNBS) and fed the experimental diets
containing 0.05% catechin and 0.025% alpha-tocopherol for 1 week, then dissected.
The extent of colitis-induced TNBS was assessed macroscopically. The
supplementation of catechins and alpha-tocopherol significantly decreased colonic
damage compared with the group fed the basal diet (the disease control). In
particular, catechin feeding completely inhibited the development of colon
adhesions. Colonic myeloperoxidase (MPO) activity, which is a marker of
neutrophil infiltration into the colonic mucosa, was lower in the groups that had
been given catechins and alpha-tocopherol. The levels of thiobarbituric acid
reactive substances in colon was highest in the disease control group; however,
the differences among the groups were not significant. Plasma alkaline
phosphatase activity was maintained at normal levels in the rats supplemented
with catechins and alpha-tocopherol. These results suggest that catechins and
alpha-tocopherol have anti-inflammatory effects on TNBS-induced rat colitis.
PMID- 10197309
TI - Vitamin E reduces glucocorticoid-induced oxidative stress in rat skeletal muscle.
AB - The purpose of this study was to investigate the effect of vitamin E on oxidative
stress in the skeletal muscle of glucocorticoid-treated rats. Male Sprague-Dawley
rats (5 weeks of age) were fed a basal diet or a diet supplemented with vitamin E
(5,000 mg DL-alpha-tocopheryl acetate/kg diet) for 10 d. The rats of both diet
groups received subcutaneous injections of corticosterone (CTC) (0, 25, and 100
mg/kg body weight/d) during the final 4 d. Weights of the extensor digitorum
longus and gastrocnemius (GAST) muscles were dose-dependently reduced by CTC.
However, the muscle weight losses in rats fed the vitamin E diet were smaller
than those in rats fed the basal diet. Protein carbonyl content in the GAST
muscle, which was determined as an index of oxidatively modified protein, was
increased by 100 mg of CTC, and the increment was significantly (p < 0.01)
reduced by vitamin E supplement. Hyperglycemia was induced by 100 mg of CTC, but
it was not affected by vitamin E. Lipid peroxide (TBARS) in plasma and in GAST
muscle was elevated by 100 mg of CTC, and vitamin E significantly (p < 0.001)
suppressed the formation of TBARS in the muscle. The change in TBARS paralleled
that in protein carbonyl. These results show that CTC leads to oxidative stress
in rat skeletal muscles and that vitamin E has roles in reducing the oxidative
stress which causes muscle atrophy.
PMID- 10197310
TI - Transitory laxative threshold of trehalose and lactulose in healthy women.
AB - The transitory laxative threshold of a partially digestible disaccharide,
trehalose, and an undigestible disaccharide, lactulose, was estimated by the dose
response relation between the test substance and the prevalence of diarrhea in 20
healthy female subjects. The subjects ingested several indicated amounts of
trehalose or lactulose once daily 2 to 3 h after a meal. The intake of the test
substance was stopped at the dose level that caused diarrhea or when the dose
reached the maximal level. A record of physical conditions, gastrointestinal
symptoms, and fecal conditions was made by all subjects before and after each
ingestion of the test substance. Half the subjects experienced no diarrhea even
with the ingestion of the maximal dose level (60 g) of trehalose in this study,
and the ingestion of up to 40 g of lactulose caused diarrhea in 75% of all
subjects. Abdominal symptoms such as flatus, distension, and borborygmus appeared
at high prevalence with lactulose and trehalose ingestion, and the effect of
lactulose was significantly stronger than that of trehalose at the same dose
level (p < 0.05). The quantity of trehalose and lactulose that induced diarrhea
differed greatly from person to person. The transitory laxative threshold was
estimated as 0.65 g/kg body weight for trehalose and 0.26 g/kg body weight for
lactulose by using the regression equation between the dose levels of the test
substances and the cumulative incidence of diarrhea. These results suggest that
it would be quite acceptable to administer trehalose up to 33 g and lactulose up
to 13 g in a person weighing 50 kg.
PMID- 10197311
TI - Effects of thyroid hormones on myofibrillar proteolysis and activities of
calpain, proteasome, and cathepsin in primary cultured chick muscle cells.
AB - The effects of thyroxine (T4) and triiodothyronine (T3) on growth, muscle protein
degradation, and proteases activities in cultured chick muscle cells were
studied. The cells were treated with a physiological level of T4 (60 ng/mL) or T3
(12 ng/mL) for 6 d. Calpain, cathepsins, and proteasome activities and N tau
methylhistidine release were measured as indexes of myofibrillar protein
breakdown. Creatine kinase activity was also measured as an index of myotube
formation. Calpain activity was increased by T4 and T3. Cathepsin D and
proteasome activities and N tau-methylhistidine release were increased by T3, but
not by T4. Neither were cathepsin B and B + L activities affected by T3 or T4.
Creatine kinase activity was increased by T4 and T3. The results suggest that
myotube formation is accelerated by T4 and T3, whereas myofibrillar protein
degradation is accelerated by T3, but not by T4.
PMID- 10197312
TI - The significance of plasma lysophospholipids in patients with renal failure on
hemodialysis.
AB - Abnormal phospholipid metabolism may play an important role in the progression of
atherosclerosis in renal failure. We analyzed plasma phospholipid and
lysophospholipid contents and fatty acid composition in the phospholipids of 18
patients with renal failure on hemodialysis (HD) and compared the levels with
those of healthy controls. HD patients had a notably higher molar ratio of the
plasma lysophosphatidylcholine (lysoPC)/phosphatidylcholine (PC) distributed from
0.072 to 0.207, and the control group showed a ratio lower than 0.150. Plasma
phosphatidylethanolamine (PE) concentration significantly increased in HD
patients compared with control subjects. A much higher level of plasma
lysophosphatidic acid (lysoPA) (1.41 +/- 0.16 nmol/mL) was observed in HD
patients compared with controls (0.54 +/- 0.08 nmol/mL). A strong correlation was
found between plasma lysoPA and lysoPC concentrations (r = 0.609, p < 0.01) in HD
patients. Serum inorganic phosphate (P) concentration was associated with the
abnormal plasma lysoPC/PC, PE, and lysoPA levels in HD patients. Important
decreases in eicosapentaenoic acid (EPA) of plasma PC and of dietary intake were
observed in HD patients. Plasma thiobarbituric acid reactive substance (TBARS)
concentration was negatively correlated with the amount of vitamin E intake in
both subjects. These findings demonstrated the specific characteristics of the
abnormal phospholipid metabolism in HD patients. The cause and consequences of
elevated lysoPC/PC molar ratio and lysoPA in the plasma of HD patients remain to
be established.
PMID- 10197313
TI - Evaluation of fasting serum insulin levels among Japanese school-age children.
AB - We examined the physical constitution, serum lipids, fasting serum insulin (IRI),
food intake, and physical activity in 1,330 children in three age groups (6-7, 9
10, and 12-13) in Nagao village for the period 1994-1996. Serum total cholesterol
(TC) and high-density lipoprotein-cholesterol (HDL-C) levels were positively
correlated, and HDL-C and TG were negatively correlated in all age groups. IRI
was significantly higher among the elder children, and it was also higher in
girls than in boys. IRI was positively correlated with the body mass index (BMI)
and triceps skinfold thickness in ages 9-10 and 12-13, but no significant
correlation was noted with waist/hip ratio (W/H ratio). In ages 12-13, IRI was
positively correlated with TC and TG and negatively correlated with HDL-C. In
high-IRI children (above 11.4 microU/mL) ages 12-13, the high-fat diet (fat
energy ratio above 30%) and low physical activity children (physical activity
score below 10 points) were more frequent, and the mean levels of triceps
skinfold were higher. The positive correlation between TC and HDL-C was not
significant among high-IRI children. We concluded that a high-fat diet, low
physical activity, and body fat accumulation influence the IRI level, which is
closely related to serum lipid levels.
PMID- 10197314
TI - Ameliorating effects of water-soluble polysaccharides from woody ear (Auricularia
auricula-judae Quel.) in genetically diabetic KK-Ay mice.
AB - We investigated the ameliorating effects of the three groups of water-soluble
polysaccharides, a mixture of crude polysaccharides (FA), acidic polysaccharide
fractions (FA-A), and neutral polysaccharide fractions (FA-N), obtained from the
hot water extracts of the fruit bodies of Auricularia auricula-judae Quel. In
genetically diabetic KK-Ay mice from 6 to 11 weeks of age. Male mice were divided
into five dietary groups: 1) control group, given a basal diet; 2) FA group,
given an FA diet (15 g FA/kg diet); 3) FA-A group, given an FA-A diet (8 g FA
A/kg diet); 4) low FA-N group, given a low FA-N diet (2 g FA-N/kg diet); and 5)
high FA-N group, given a high FA-N diet (8 g FA-N/kg diet). Compared with the
control diet, FA supplementation had significant effects in lowering fasting and
nonfasting blood glucose, HbA1c, urinary glucose, food intake, and water intake.
FA administration also improved glucose tolerance to intraperitoneal glucose
loading, but it did not affect the nonfasting insulin level. FA-N supplementation
had dose-dependent effects in lowering fasting and nonfasting food glucose,
insulin, HbA1c, urinary glucose, food intake, and water intake. However, the
glucose tolerance was not ameliorated by either the low or the high FA-N diet. FA
A administration showed no beneficial effects in KK-Ay mice.
PMID- 10197315
TI - Class specific influence of dietary Spirulina platensis on antibody production in
mice.
AB - In the present study, we investigated antibody productions of IgA and other
classes, such as IgE and IgG1, in mice as possible evidence of the protective
effects of Spirulina toward food allergy and microbial infection. An increase of
IgE antibody level in the serum was observed in the mice that were orally
immunized with crude shrimp extract as an antigen (Ag group). The antibody level,
however, was not further enhanced by treatment with Spirulina extract (SpHW).
IgG1 antibody, on the other hand, which was increased by antigen administration,
was further enhanced by Spirulina extract. It was noted that the IgA antibody
level in the intestinal contents was significantly enhanced by treatment with
Spirulina extract concurrently ingested with shrimp antigen, in comparison with
that of the Ag group treated with shrimp antigen alone. An enhancement of IgA
antibody production by Spirulina extract was also observed in culture supernatant
of lymphoid cells, especially in the spleen and mesenteric lymph node from mice
treated with Spirulina extract for 4 weeks before antigen stimulation. These
results suggest that Spirulina may at least neither induce nor enhance allergic
reaction such as food allergy dependent on an IgE antibody, and that when
ingested both concurrently with antigen and before antigen stimulation, it may
significantly enhance the IgA antibody level to protect against allergic
reaction.
PMID- 10197316
TI - An inverse relationship between serum vitamin C and blood pressure in a Japanese
community.
AB - To examine the relationship between serum vitamin C concentration and blood
pressure level, a cross-sectional study was conducted. The subjects were 919 men
and 1,266 women aged 40 years and over in a Japanese provincial city, Shibata,
Niigata Prefecture. The mean and standard deviation of systolic blood pressure
(SBP) were 134.0 +/- 20.0 mmHg for men and 128.3 +/- 20.8 mmHg for women, and
those of diastolic blood pressure (DBP) were 81.0 +/- 11.7 mmHg and 75.8 +/- 11.4
mmHg, respectively. The mean and standard deviation of serum vitamin C were 42.5
+/- 18.6 mumol/L for men and 56.8 +/- 16.5 mumol/L for women. SBP and DBP were
both inversely correlated with serum vitamin C concentration. The means of SBP or
DBP were calculated for quartiles of serum vitamin C, and the significant inverse
relationship was observed in any sex and age group. The inverse association
persisted after adjustment for possible confounders: body mass index, serum total
cholesterol, alcohol consumption, smoking, physical activity, antihypertensive
medication, and dietary intake of salt, calcium, and potassium. Serum vitamin C
appeared to be inversely related with both SBP and DBP in this Japanese
population, although further intervention and experimental studies were required
to establish the cause-effect relationship.
PMID- 10197317
TI - Effect of L-lactic acid on the absorption of calcium in gastrectomized rats.
AB - The effect of dietary L-lactic acid (LA), (0.5, 1.0, or 2.5 g/100 g of diet) on
the absorption of calcium in gastrectomized rats was evaluated for 28 d. Calcium
phosphate was used as a source of calcium. The apparent calcium absorption ratio
and the calcium contents of the femur and tibia in gastrectomized rats fed the
control diet were significantly less than those in sham-operated rats. In the
gastrectomized rats, the apparent calcium absorption ratio and the calcium
contents of bone in the rats fed the lower doses of LA diets (LA 0.5 or 1.0 g/100
g of diet) were not affected; however, the apparent calcium absorption ratio and
the calcium contents of bone in the rats fed the highest doses of LA diet (LA 2.5
g/100 g of diet) were greater than those in gastrectomized rats fed the control
diet. Dietary LA (2.5 g/100 g of diet) also enhanced the phosphorus absorption
and bone phosphorus content in the gastrectomized rats. We speculated that the
highest dose of dietary LA might be associated with the dissolving of a water
insoluble form of calcium salt in the diet, thereby facilitating the calcium
absorption and resulting in increased bone calcium content in gastrectomized
rats.
PMID- 10197318
TI - Fermentation of soybean flour with Aspergillus usamii improves availabilities of
zinc and iron in rats.
AB - Soybean flour was fermented with Aspergillus usamii to improve the availabilities
of dietary zinc and iron through the degradation of phytate. Three kinds of
experimental diets that differed in protein sources were prepared: one consisting
of 40% fermented soybean flour (RS diet), one consisting of 40% fermented soybean
flour (FS diet), and one consisting of 20% regular soybean flour and 20%
fermented soybean flour (RF diet). Zinc solubilities in the upper and the lower
segments of the small intestine were higher in rats fed the FS diet than in rats
fed the RS diet. The FS group showed higher solubility of iron in the lower small
intestine than the RS group did. Zinc concentrations in the femur and plasma and
iron concentrations in the liver and plasma were higher in the FS group than in
the RS group. These results suggested that the fermentation of soybean flour
improved the availabilities of dietary zinc and iron, which may be induced by
increasing the solubilities of these minerals in the small intestine through the
reduction of phytate content. Femoral and plasma zinc concentrations in the RF
group were higher than in the RS group, but lower than in the FS group. No
difference was noted in liver and plasma iron concentrations between the RF group
and the FS group. Although phytase activity in FS degrades phytate in the RF
diet, higher activity may be needed to degrade phytate completely.
PMID- 10197319
TI - Absorbability of calcium from a new calcium supplement prepared from bovine
marrow-free bone in rats.
AB - Powdered bovine marrow-free bone was completely solubilized with lactic and
citric acids under reduced pressure. The resulting solution was lyophilized to
obtain a stable powder form (total bone extract, TBE), and the calcium (Ca)
absorbability of TBE from intestine was investigated in normal rats. Each animal
perorally received 10 mg of Ca in 1 mL of distilled water as extrinsic 45Ca
labeled TBE, intrinsic 45Ca-labeled Ca lactate, or intrinsic 45Ca-labeled Ca
carbonate. The amount of radioactivity in plasma was measured periodically up to
34 h after dosing, and pharmacokinetic parameters were calculated from the
radioactivity in plasma. The time taken to reach the maximal 45Ca level (Tmax)
did not differ among the three groups. The area under the plasma 45Ca level/time
curve (AUC infinity) and the radioactivity at Tmax (Cmax) values for the TBE
group were significantly higher than those of the Ca carbonate group. Similar
results were observed between the Ca lactate and the Ca carbonate groups. No
significant difference was observed in the AUC infinity and the Cmax values
between the TBE and the Ca lactate groups. Radioactivity in a femur 34 h after
dosing was highest in the Ca lactate group and lowest in the Ca carbonate group
among the three groups. Both the TBE and the Ca lactate groups showed significant
higher whole-body 45Ca retention than the Ca carbonate group did, although no
significant difference was found between the TBE and the Ca lactate groups. These
findings indicate that the Ca absorbability of TBE is almost comparable with that
of Ca lactate and higher than that of Ca carbonate. Therefore TBE would be useful
as a Ca supplement with relatively high absorbability from intestine.
PMID- 10197320
TI - The placebo "arm".
PMID- 10197321
TI - Comparative study of the clinical efficacy of two different coumarin dosages in
the management of arm lymphedema after treatment for breast cancer.
AB - In a randomized, double-blind, parallel group study, we compared the clinical
efficacy of coumarin 90 mg/day (Group A) with 135 mg/day (Group B) in 77 women
(age 35-65 years) with lymphedema of the upper limb secondary to surgery and
irradiation for treatment of breast cancer. During 12 months of coumarin therapy,
the arm volume of lymphedema and a clinical score (degree of arm edema,
heaviness, hardness, and neuralgia/dysesthesia) were determined. In both groups,
the volume of arm lymphedema decreased (14.9% in Group A and 13.2% in Group B)
(N.S.), the overall clinical score improved (12.9 +/- 4.3 to 5.7 +/- 3.5 in Group
A and from 11.7 +/- 3.7 to 4.7 +/- 3.9 in Group B) (N.S.), and the overall
efficacy of coumarin was similarly good or excellent (71.9% in Group A and 68.6%
in Group B) (N.S.). Only mild to moderate side effects of drug therapy were
recorded. Coumarin prevents a spontaneous trend toward an increase in arm
lymphedema after treatment of breast cancer, decreases the severity of local
symptoms, and overall improves the quality of life. No difference was found
between the apparent benefits of coumarin at 90 mg/day compared with 135 mg/day.
PMID- 10197322
TI - Venous dynamics in leg lymphedema.
AB - To determine whether there is anatomical and/or functional impairment to venous
return in patients with lymphedema, we examined venous dynamics in 41 patients
with unilateral leg lymphedema. A Volometer was used for computer analysis of leg
volume, a color Duplex Doppler scanner was used to determine deep vein patency
and skin thickness, and Air-plethysmography was used to assess ambulatory venous
pressure, venous volume, venous filling index and the ejection fraction. In the
lymphedematous leg, volume and skin thickness were uniformly increased (126.4 +/-
21.3% and 156.9 +/- 44.5%) (mean +/- S.D.), respectively. The ambulatory venous
pressure was also increased (134 +/- 60.7%) as was the venous volume (124.5 +/-
37.5%), and the venous filling index (134.5 +/- 50.5%). The ejection fraction was
decreased (94.9 +/- 26.1%). Greater leg volume correlated with increased venous
volume and venous filling index (values = 0.327, 0.241, respectively) and
decreased ejection fraction (r = -0.133). Increased subcutaneous thickness
correlated with increased venous filling index and venous volume (r = 0.307,
0.126, respectively) and decreased ejection fraction (r = -0.202). These findings
suggest that soft tissue edema from lymphatic stasis gradually impedes venous
return which in turn aggravates the underlying lymphedema.
PMID- 10197324
TI - Analysis of thoracic duct flow waves using fast Fourier transform in sheep.
AB - We measured the lymph flow of the thoracic duct using an ultrasound transit-time
flowmeter and then analyzed the obtained flow signals by fast Fourier transform.
We found that the wave form included a low frequency component (approximately 0.1
Hz) as well as high frequency components which represented cordiac pulsation and
respiratory movement. The low frequency component signified an intrinsic thoracic
duct pulsation. When venous outflow pressure was increased, the frequency of the
thoracic duct pulsation increased, whereas the frequencies of cardiac pulsation
and respiratory movement were unchanged. These findings suggest that thoracic
duct pulsation is independent of cardiac pulsation and respiratory movement.
PMID- 10197323
TI - Changes in lymphatic function after complex physical therapy for lymphedema.
AB - Twenty-two extremities of 19 lymphedema patients (6 arms, 16 legs) were treated
by 2 weeks of complex physical therapy (CPT) and self home maintenance therapy
(bandage/wearing of elastic garment and exercise). In addition to the clinical
response of volume reduction before and 3 months after CPT, we analyzed the
functional changes of the peripheral lymphatic system by use of
lymphoscintigraphy (LS). Before CPT, the main LS findings of lymphedema included
dermal backflow (100%), absent or faintly visualized regional lymph nodes
(95.5%), presence of collateral lymphatic vessels (68.2%), and no or barely
visualized lymphatic vessels (27.3%). LS findings suggesting improved lymphatic
function after CPT were a decrease in dermal backflow (72.7%), an increase in
radioisotope uptake by lymphatic vessels (27.3%), and an increase in radioisotope
uptake by lymph nodes (9.1%). 81.8% of limbs showed improved lymphoscintigraphic
findings and no change in 9.1%. In the others (9.1%), LS findings appeared worse.
There was, however, no correlation between LS "improvement" and the amount of
limb volume reduction.
PMID- 10197325
TI - Failure of the canine principal ascending epicardial lymphatic to regenerate
after transection.
AB - We transected the principal ascending anterior epicardial cardiac lymphatic in 10
dogs, and after varying time intervals reoperated to look for lymphatic
regeneration using dye injection. Photographs and sketches were made to record
the findings, and in six dogs serial histologic sections were also examined. In
none of the 10 dogs was regeneration of the transected principal cardiac
lymphatic detected although small lymphatic collaterals from the distal side of
the lymphatic developed in 2 dogs. Further studies are merited to assess the role
of lymphatic insufficiency in the development of coronary vasculopathy and
chronic rejection after cardiac transplantation and other heart operations (e.g.,
coronary artery bypass) that may injure lymphatic drainage capacity.
PMID- 10197326
TI - Basic contributions to lymphology.
PMID- 10197327
TI - [Proceedings of 28th annual meeting of the Japanese Society of
Neuropsychopharmacology. Tokyo, Japan. October 21-23, 1998. Abstracts].
PMID- 10197328
TI - Gender shifts.
PMID- 10197329
TI - Fentanyl dosage.
PMID- 10197330
TI - Dental caries and fluorosis among children in a rural Georgia area.
AB - PURPOSE: This IRB-approved study compared the caries experience, fluorosis
prevalence, and plaque and salivary fluoride concentrations ([F]) in middle
school (MS; N = 51) and elementary school (ES; N = 144) children residing in
nonfluoridated and fluoridated communities in rural Georgia. All participants
were exposed to fluoridated water at school (0.5-1.2 ppm), some received that
level at home, and others received home water with < 0.1 ppm F. METHODS:
Subjects' parents completed a questionnaire regarding fluoride exposure. Children
were examined at school by two calibrated dentists. RESULTS: No significant
differences were seen in DMFS+dfs between children with or without fluoridated
home water, nor for those with or without fluorosis. MS children with non
fluoridated home water had lower mean salivary [F] values than MS children with
fluoridated home water. No differences were found among MS and ES children in
mean plaque [F] for those with or without fluorosis. CONCLUSIONS: Home water
fluoridation had little effect on the variables measured. These findings appear
to be due to fluoride exposure from fluoridated dentifrices, fluoridated drinking
water at school, and the fluoride "halo" effect.
PMID- 10197331
TI - Investigation of the role of human breast milk in caries development.
AB - PURPOSE: The objective of this study was to determine the caries-related risk
associated with human breast milk (HBM). METHODS: First, the plaque pH of 18
children (12-24 months) was monitored before and after a five-minute feeding with
HBM to determine the pH drop and minimum pH obtained. Second, Streptococcus
sobrinus 6715 was cultured for 3 hr in HBM, and the increase in the number of
colony forming units (cfus) and the culture pH was measured. Third, HBM was
incubated for 24 hr with powdered enamel to determine the solubility of mineral
in the absence of bacteria. Fourth, HBM was mixed with acid to determine the
buffering capabilities. Finally, enamel windows were created on extracted
premolar crowns (N = 33) that were colonized with Mutans Streptococci and
incubated with HBM. Caries was assessed visually and radiographically for 12
weeks. RESULTS: One- and two-way ANOVAs of these five assays demonstrated that
HBM did not cause a significant drop in plaque pH when compared to rinsing with
water; HBM supported moderate bacterial growth; calcium and phosphate were
actually deposited onto enamel powder after incubation with HBM; the buffer
capacity of HBM was very poor; and HBM alone did not cause enamel decalcification
even after 12 weeks exposure. However, when supplemented with 10% sucrose, HBM
caused dentinal caries in 3.2 weeks. CONCLUSION: It is concluded that human
breast milk is not cariogenic.
PMID- 10197332
TI - Prevalence of caries in urban Australian aborigines aged 1-3.5 years.
AB - PURPOSE: This study investigated the prevalence and etiological factors
associated with caries in a group of young Australian aboriginal children from 1
to 3.5 years of age. METHODS: One hundred and forty-seven healthy infants, aged
from 1 to 3.5 years, attending a community health center in Brisbane, a
nonfluoridated state capital city, were randomly selected for the study. RESULTS:
The caries prevalence was 39% by subjects and 32% by the total number of teeth
present. The mean number of decayed, filled teeth (dtf) was 2.5 +/- 0.4, which is
more than twice the figure for 3-year-old children in Australia. Furthermore, the
filled (f) component represented only 1% of the total dft, suggesting very low
treatment levels. Increased caries experience of the infants was strongly
associated with high dental plaque scores, high levels of Streptococcus mutans
infection, and sleep-time consumption of milk containing added sugar. CONCLUSION:
The results suggest that urban Australian aboriginal infants are at high risk for
caries, and that preventive strategies are urgently required.
PMID- 10197333
TI - Children's utilization of dental care in the NC Medicaid program.
AB - PURPOSE: To characterize the patterns of dental care in the North Carolina (NC)
Medicaid Program for three- and eight-year-old children who began dental
treatment in the 1985-86 and 1990-91 groups. We also compared the children's
patterns of care by provider (general dentists versus pediatric dentists).
METHODS: Our extensive data set included claims, enrollment, and provider data.
Children were assigned to one of five categories or patterns of care as follows:
complete care, general anesthesia care, sporadic care, emergency only care, and
no care. Statistical comparisons of the variables age, cohort year, and provider
groups were made. RESULTS: The use of Medicaid dental services by both age groups
was severely limited in both yearly cohorts. Pediatric dentists tended to provide
more complete and less sporadic care for both age groups and both yearly cohorts.
CONCLUSIONS: Financing dental care through Medicaid results in very low levels of
complete care among enrollees, and any plan that limits referral to pediatric
dentists might adversely affect the number of enrollees who receive complete
care.
PMID- 10197334
TI - A survey of private pediatric dental practices in North Carolina.
AB - PURPOSE: In response to concerns about current and future demands for specialized
pediatric dental care in North Carolina, a survey of private pediatric dental
practices was conducted. METHODS: Data were collected on the demographics and
other practice variables. Information was also collected on the ages, caries
activity, Medicaid status, estimated treatment needs, fluoridation status, and
location of residence (urban/rural) of all new patients seen in each practice
during three designated, consecutive days in November 1996. RESULTS: The survey
response rate was 76%. The data indicated that most pediatric dentists in North
Carolina are quite busy. A total of 519 new patients were seen during the three
day survey period. The mean age was 4.7 years and 22% had advanced caries. Forty
seven percent were caries free. Most of the disease was found in the primary
dentitions of young children. CONCLUSIONS: The findings indicate that the
specialized pediatric dental care system in North Carolina is operating close to
its capacity and is overtaxed in many areas of the state.
PMID- 10197335
TI - The effect of dental rehabilitation on the body weight of children with early
childhood caries.
AB - PURPOSE: The purpose of this study was to determine the effect of comprehensive
dental rehabilitation on the percentile weight and percentile growth velocity of
children with early childhood caries (ECC). METHODS: The percentile weight
categories of children with noncontributory medical histories and ECC were
compared to caries free comparison patients, before and after comprehensive
dental treatment under general anesthesia. RESULTS: Prior to dental
rehabilitation, test subjects' percentile weight categories were significantly
less than that of comparison counterparts (P < 0.001). Of the ECC patients, 13.7%
weighed less than 80% of their ideal weight, thereby satisfying one of the
criteria for the designation of failure to thrive, while none of the comparison
patients did so (P < 0.05). Following therapeutic intervention, ECC children
exhibited significantly increased growth velocities through the course of the
follow-up period (P < 0.001), reflecting the phenomenon of catch up growth. The
average length of follow-up for the test and comparison groups were 1.58 and 1.36
years, respectively. At the end of the follow-up period there were no longer any
statistically significant differences noted in the percentile weight categories
of the test and comparison groups. CONCLUSION: Comprehensive dental
rehabilitation resulted in catch-up growth, such that children with a history of
nursing caries no longer differed in percentile weights from comparison patients.
PMID- 10197336
TI - Mercury exposure due to environmental factors and amalgam restorations in a
sample of North Carolina children.
AB - PURPOSE: Dental amalgam restorations provide a potential source for mercury (Hg)
exposure in children. This study explored the possibility that Hg levels in
dentin of exfoliated primary maxillary canines could detect cumulative Hg
exposure from amalgam restorations in a sample of North Carolina children.
METHODS: Twenty-seven exfoliated maxillary canines from 3.3 children, without
restorations or caries, were assayed for dentin Hg concentration ([Hg]). Urine
samples were obtained from 21 subjects and assayed for [Hg] and diet surveys for
seafood ingestion were completed for 26 subjects. A surface/month exposure index
(SMEI) was compiled from dental records to quantify each child's cumulative
exposure to amalgam restorations. RESULTS: Results showed that dentin [Hg] ranged
from undetectable levels to 15.7 ppm with a mean of 3.7 ppm. The SMEI scores
ranged from 0-638 with a mean of 95. Ten subjects had low SMEI scores of 0-3,
nine had scores 4-100, and eight had scores higher than 100. No statistical
correlation was found for SMEI scores and dentin [Hg]. Urine Hg levels were found
to be negligible and no relationship was found between urine [Hg] and reported
ingestion of seafood or SMEI scores. CONCLUSIONS: Hg exposure in this sample of
children was low and additional exposure from amalgam restorations could not be
detected by the methods used in this study.
PMID- 10197337
TI - Composite resin support of undermined enamel in amalgam restorations.
AB - PURPOSE: Previous reports suggested that cusp fracture strength increases with
the use of bonded composites. The purpose of this study was to assess fracture
resistance of undermined cusps, when supported by a layer of bonded composite, in
extensive occlusal carious lesions. METHODS: Primary and permanent molars in
children that were treated included those with extensive occlusal caries with
undermined enamel in one or more cavity walls. Following local anesthesia and
rubber dam application, cavity outline was prepared with a #330 tungsten bur, and
the carious lesion removed. If an unsupported cusp was present, the inner enamel
wall and the dentine floor adjacent to this wall was etched with a gel containing
37% phosphoric acid, rinsed and dried and Scotch bond multipurpose applied; a 1
mm layer of Z100 was applied to the unsupported cusp and polymerized; a nongamma
2 amalgam or Z100 was used to restore the tooth. RESULTS: The children were re
examined after 6, 12 or 24 months. A total of 42 restorations were placed in 39
children (26 boys and 13 girls), ranging in age from 4 to 16 years (mean age 9
years, 6 months). This is a preliminary report on 30 restorations, followed up
from 6 to 24 months. All 30 restorations were successful in preventing cuspal
fracture. Four teeth developed caries in the proximal surface, but were unrelated
to the restoration. CONCLUSIONS: It was concluded that bonded composite can
prevent fracture of unsupported cusps.
PMID- 10197338
TI - Light-hardened luting cement for orthodontic bands and appliances.
PMID- 10197339
TI - The Wand.
PMID- 10197340
TI - Pulse oximetry evaluation of vitality in primary and immature permanent teeth.
AB - Present methods of assessing pulp vitality (electric and thermal testing) are of
limited use with children, often resulting in false positive or false negative
results. Pulse oximetry is a proven, atraumatic method of measuring vascular
health by evaluating oxygen saturation (SaO2). This pilot study explores the use
of a modified pulse oximetry ear probe to assess pulpal vascular oxygen
saturation in primary and immature permanent teeth. Pulse oximetry readily
differentiated between known vital and nonvital teeth. Vital teeth consistently
provided SaO2 values that were lower than the values recorded on the patients'
fingers. Further study of the SaO2 changes in traumatized teeth, with a probe
designed specifically for teeth, is warranted by these initial results. Although
additional research is indicated, pulse oximetry is already an objective,
atraumatic clinical alternative to the present electrical and thermal methods of
assessing pulp vitality in children's teeth.
PMID- 10197341
TI - Laser pulpotomy of primary teeth.
PMID- 10197342
TI - Dentin malformation with alveolar bone loss and periapical abscess formation.
PMID- 10197343
TI - Aspiration of gauze pressure-pack following a dental extraction: a case report.
PMID- 10197345
TI - Modeling of the correlation of analytic ultrasound radiofrequency signals for
angle-independent motion detection.
AB - Conventional pulsed ultrasound systems are able to assess motion of scatterers in
the direction of the ultrasound beam, i.e., axial motion, by determining the lag
at which the maximum correlation occurs between consecutively-received
radiofrequency (rf) signals. The accuracy, resolution, and processing time of
this technique is improved by making use of a model for the correlation of rf
signals. All previously-described correlation models only include axial motion,
but it is common knowledge that lateral motion, i.e., motion in the plane
perpendicular to the beam axis, reduces the correlation of rf signals in time. In
the present paper, a model for the correlation of analytic rf signals in depth
and time is derived and verified. It also includes, aside of some signal and
transducer parameters, both axial and lateral motion. The influence of lateral
motion on the correlation of (analytic) rf signals is strongly related to local
phase and amplitude characteristics of the ultrasound beam. It is shown how the
correlation model, making use of an ultrasound transducer with a circular beam
shape, can be applied to estimate, independent of angle, the magnitude of the
actual motion. Furthermore, it is shown that the model can be applied to estimate
the local signal-to-noise ratio and rf bandwidth.
PMID- 10197344
TI - The esthetic stainless steel crown bridge: report of two cases.
PMID- 10197346
TI - Effective density estimators based on the K distribution: interest of low and
fractional order moments.
AB - The K distribution is an efficient model to the nonRayleigh statistics of the
envelope of backscattered signals in random media. This modeling leads to
estimate a parameter of effective density by means of the calculation of
statistical moments of the envelope signal. In this study, we propose a
mathematical analysis of an effective density estimator previously used and based
on superior order moments. In order to improve the effective density estimate, we
propose several estimators based on low and fractional order moments. The
performances of these estimators are evaluated both with simulated signals and in
an experimental context with synthetic foams. Estimators based on low and
fractional moments appear to be more robust than superior moment-based estimator
and an improvement of the spatial resolution of the estimate can be obtained.
Results also confirm the capability of the effective density parameter to
characterize the spatial distribution of scattering structures.
PMID- 10197347
TI - Elastic moduli of breast and prostate tissues under compression.
AB - To evaluate the dynamic range of tissue imaged by elastography, the mechanical
behavior of breast and prostate tissue samples subject to compression loading has
been investigated. A model for the loading was validated and used to guide the
experimental design for data collection. The model allowed the use of small
samples that could be considered homogeneous; this assumption was confirmed by
histological analysis. The samples were tested at three strain rates to evaluate
the viscoelastic nature of the material and determine the validity of modeling
the tissue as an elastic material for the strain rates of interest. For loading
frequencies above 1 Hz, the storage modulus accounted for over 93 percent of the
complex modulus. The data show that breast fat tissue has a constant modulus over
the strain range tested while the other tissues have a modulus that is dependent
on the strain level. The fibrous tissue samples from the breast were found to be
1 to 2 orders of magnitude stiffer than fat tissue. Normal glandular breast
tissue was found to have an elastic modulus similar to that of fat at low strain
levels, but the modulus of the glandular tissue increased by an order of
magnitude above fat at high strain levels. Carcinomas from the breast were
stiffer than the other tissues at the higher strain level; intraductal in situ
carcinomas were like fat at the low strain level and much stiffer than glandular
tissue at the high strain level. Infiltrating ductal carcinomas were much stiffer
than any of the other breast tissues. Normal prostate tissue has a modulus that
is lower than the modulus of the prostate cancers tested. Tissue from prostate
with benign prostatic hyperplasia (BPH) had modulus values significantly lower
than normal tissue. There was a constant but not significant difference in the
modulus of tissues taken from the anterior and posterior portions of the gland.
PMID- 10197348
TI - Determination of ultrasonic parameters based on attenuation and dispersion
measurements.
AB - In the measurement of acoustic attenuation that obeys a power-low alpha = beta f,
the traditional through-transmission method uses only the amplitude information
of the recorded pulses to determine the two parameters, beta and n. In this
paper, we propose a new method that utilizes both the amplitude and phase
information of the pulses to determine the two parameters. According to this
method, the two parameters are estimated by simultaneously performing a least
squares fit to the attenuation data that are derived from the amplitude spectra
of the pulses, and to the dispersion data that are derived from the phase spectra
of the pulses. By fully utilizing the information contained in the recorded
pulses and imposing additional constraints on the two parameters, the estimation
uncertainty can be reduced. Experimental results from two specimens, one having a
linear attenuation and one having a nonlinear attenuation, demonstrate that the
new method produces a moderate variance reduction in the case of linear
attenuation, and a significant variance reduction in the case of nonlinear
attenuation.
PMID- 10197349
TI - Ultrasonic imaging of the electroacoustic effect in macromolecular gels.
AB - The electroacoustic effect occurs in electrolytes and colloidal suspensions. It
describes the phenomenon in which a voltage applied to the sample produces an
acoustic signal or vice versa. The basic mechanism is that charged particles in
the sample have various mobilities due to different masses and viscosities. Under
an external voltage they respond differently to the electrical force. This
results in an overall acoustic vibration. The electroacoustic effect has been the
basis for many measurement tools of solutions and other materials. In this note a
method to image macromolecular gel samples using the electroacoustic effect at
ultrasound frequencies is presented. Radiofrequency electrical excitation
produces ultrasonic signal due to spatial changes in the electroacoustic some
amplitude of the sample, which is used to construct an image similar to
ultrasonography. This method is demonstrated in agar gel and egg-white protein
phantoms. The image contrast mechanism is also discussed.
PMID- 10197350
TI - The critical evaluation of a comprehensive mass spectral library.
AB - A description of the methods used to build a high quality, comprehensive
reference library of electron-ionization mass spectra is presented. Emphasis is
placed on the most challenging part of this project--the improvement of quality
by expert evaluation. The methods employed for this task were developed over the
course of a spectrum-by-spectrum review of a library containing well over 100,000
spectra. Although the effectiveness of this quality improvement task depended
critically on the expertise of the evaluators, a number of guidelines are
discussed which were found to be effective in performing this onerous and often
subjective task. A number of specific examples of the particularly challenging
task of spectrum editing are given.
PMID- 10197351
TI - Nanoelectrospray--more than just a minimized-flow electrospray ionization source.
AB - The comparison between electrospray ionization (ESI) mass spectra from NaCl
solutions with and without analyte obtained under ionspray and nanospray
conditions reveals different mass spectral behavior of the two ESI techniques.
This can be attributed to the different initial droplet sizes which are in the
microns range for ionspray, while in nanospray they are believed to be about one
order of magnitude smaller. In the context of the widely accepted uneven-fission
model, nanospray would then enter one fission generation later; in addition, a
higher initial droplet surface charge density in nanospray results in early
fissions without extensive evaporation and thus increase in sample and salt
concentration. This rationalizes that ionspray spectra closely resemble nanospray
spectra from solutions with about one order of magnitude higher salt
concentrations, showing a higher tolerance of nanospray towards salt
contamination. When the analyte is a peptide (in a solution containing a high
molar surplus of salt), molecule ion formation effectively competes with salt
cluster ion formation; when the analyte is a sugar, it is detectable beside a
high salt concentration only with nanospray, indicating the supporting effect of
surface activity on ion release in the case of peptides. A model is presented
which explains the different mass spectral behaviour of ionspray and nanospray by
suggesting different "predominant fission pathways" depending on the size of the
initial droplets.
PMID- 10197352
TI - Theoretical calculations of glycine and alanine gas-phase acidities.
AB - The gas-phase acidities of glycine and alanine were determined by using a variety
of high level theoretical methods to establish which of these would give the best
results with accessible computational efforts. MP2, MP4, QCISD, G2 ab initio
procedures, hybrid Becke3-LYP (B3LYP) and gradient corrected Becke-Perdew (BP)
and Perdew-Wang and Perdew (PWP) nonlocal density functionals were used for the
calculations. A maximum deviation of approximately 13 and 18 kJ/mol from
experimental data was observed for the computed delta Hacid and delta Gacid
values, respectively. The best result was obtained at G2 level, but comparable
reliability was reached when the considerably less time consuming B3LYP, BP, and
PWP density functional approaches were employed.
PMID- 10197353
TI - Differentiation of isomeric photomodified oligodeoxynucleotides by fragmentation
of ions produced by matrix-assisted laser desorption ionization and electrospray
ionization.
AB - UV irradiation of oligodeoxynucleotides at 254 nm generates several different
types of DNA photoproducts, including cis-syn cyclobutane pyrimidine dimers,
pyrimidine[6-4] pyrimidone photoproducts and their Dewar valence isomers, and
thymine-adenine photoproducts (TA*). Studies of photoproducts in
oligodeoxynucleotides require the development of suitable structure determination
methods such as mass spectrometry. In an earlier study (Vollmer et al. Int. J.
Mass Spectrom. Ion Processes 1997, 165/166, 487-496), we showed that fast atom
bombardment and tandem sector mass spectrometry can be used to locate the site of
photomodification and identify most of the photoproducts of d(TATTAT). One goal
of the present research was to expand the method to the more sensitive
electrospray ionization (ESI) and matrix-assisted laser desorption/ionization
(MALDI) methods. A second goal was to test the generality of the methods by
investigating not only the photoproducts of d(TATTAT) but also those of three
other oligodeoxynucleotides, d(GTATTAT), d(GGCTATAA), and d(AATTAA). The
photoproducts of these sequences were separated by HPLC and gave characteristic
fragment ions in postsource decompositions of MALDI-produced ions and
collisionally activated decompositions of ESI-produced ions.
PMID- 10197354
TI - A nomenclature system for labeling cyclic peptide fragments.
AB - A nomenclature system for labeling fragment ions of cyclic peptides is proposed.
A fragment ion is labeled with a four-part descriptor for the general formula
xnJZ, where x is the designation for the ion (e.g., lower case a or b, as are
used for peptide fragments) and n is the number of amino acid residues in the
ion. A b ion is the usual acylium ion or isomeric equivalent consisting of n
amino-acid residues, and this ion may lose carbon monoxide to form an a ion. The
subscripts J and Z are the one-letter (upper-case) codes for the two amino-acid
residues connecting the backbone amide or ester bond, J-Z, that can be viewed as
broken to form the decomposing linear ion. The symbol J is for the N-terminal
amino-acid residue, and Z is that for the C-terminal amino-acid residue that
result from the bond cleavage. The nomenclature system is applicable to a wide
range of cyclic peptides, including depsipeptides, cyclic peptides containing
modified or unusual amino acids, cyclic peptides bearing a linear peptide moiety,
and cyclic peptides that are introduced into the gas phase as metal-ion
cationized species.
PMID- 10197355
TI - ATP and integrity of human red blood cells.
AB - In spite of the well known significance of ATP in the energy dependent life
processes, the role of ATP in maintaining cellular integrity is poorly
understood. A possible model for studying ATP dependent life processes is to
monitor the kinetics of changes seen intra/extracellularly during ATP depletion.
In our model system anticoagulated human whole blood was incubated at different
temperatures to reduce intracellular ATP without addition of any chemicals. The
red blood cells in their own plasma were incubated for several days at 4 degrees
C or at 37 degrees C, and ATP, glucose, K+, Na+, hemoglobin, water content, mean
corpuscular volume (MCV), pH and Ca2+ were analyzed in time-sequences. All the
examined parameters remained practically unchanged at 4 degrees C, while at 37
degrees C total ATP and glucose decreased parallel and after a transient increase
of MCV, the water content of red blood cells decreased. As the actual ATP fell
below 10% of the initial ATP content (at 48 h), the release of potassium sharply
increased. Release of hemoglobin started only after 96 hours of incubation.
Maximums of changes of the examined parameters were found at different time
intervals. The maximal speed of concentration changes for glucose was found at 12
24 hours of incubation and at 24-36 hours for ATP, at 48-60 hours for K+(-)Na+
and after 96 hours for hemoglobin.
PMID- 10197356
TI - The inhibition of bovine carbonic anhydrase by saccharin and 2- and 4
carbobenzoxybenzene sulfonamide.
AB - The present work demonstrates that the high-activity zinc metalloenzyme, carbonic
anhydrase (CA II) from bovine erythrocytes is inhibited by the cyclic sulfimide,
saccharin, and 2- and 4-carbobenzoxybenzene sulfonamide. A spectrophotometric
method was employed to monitor the enzymatically catalyzed hydrolysis of p
nitrophenyl acetate by following the increase in absorbance at 410 nm which
accompanies p-nitrophenoxide/p-nitrophenol formation. The more rapid enzymatic
hydration of CO2 was monitored by using a stopped-flow spectrophotometer as well
as by a modified colorimetric method of Wilbur and Anderson. The studies show
that, at a given molar ratio of inhibitor to enzyme, the degree of inhibition of
the enzymaic hydration of CO2 and hydrolysis of p-nitrophenyl acetate by the
inhibitory compounds is essentially the same. Kinetic analyses were made at 25.0
degrees at pH 6.5 (MES buffers), pH 6.9 (HEPES buffers) and pH 7.9 (HEPES
buffers) with ionic strength regulated by the addition of appropriate quantities
of sodium sulfate. Lineweaver-Burk plots were used to evaluate apparent
inhibition constants for each of the three inhibitors. For all the inhibitors
studied, inhibition appears to be mixed (competitive/noncompetitive). For
saccharin in the presence of sodium sulfate, the extent of inhibition is
considerably decreased. It was found for the three inhibitors that the inhibitory
potency decreases with increasing pH, and that the inhibitory potency is
extremely sensitive to the shape of these rather closely related molecules. For
example, apparent inhibition constants for the enzymatic hydrolysis of p
nitrophenyl acetate at pH 6.9 were Ki (saccharin) = 0.20 mM, Ki (2
carbobenzoxybenzene sulfonamide) = 0.54 mM and Ki (4-carbobenzoxybenzene
sulfonamide) = 1.6 microM. For the enzymatic hydration of CO2 at pH 6.9, 0.10 mM
saccharin caused 50% inhibition while 7.0 nM 4-carbobenzoxybenzene sulfonamide
resulted in 50% inhibition. The results suggest that sulfonamide inhibition is
caused by formation of a monodentate ligand at the zinc ion of the enzyme active
site and that the more linear 4-carbobenzoxybenzene sulfonamide is better able to
enter a conical enzyme active site than is 2-carbobenzoxybenzene sulfonamide or
saccharin.
PMID- 10197357
TI - Distribution profile and in vivo RNA association of cytoplasmic AU-rich sequence
binding proteins in various mammalian cells: effect of the organizational state
of cellular architecture.
AB - With the aid of sequential detergent fractionation and label transfer techniques,
in this study we monitored the distribution of cytoplasmic AU-rich sequence
binding proteins (AUBP) in different cell types. We show here that cells of
various origin display diverse AUBP profiles when the presence and abundance of
AUBPs were compared in two major cytoplasmic compartments, the non-ionic
detergent-soluble and -insoluble fractions. We also demonstrate that different
RNA probes derived from AU-rich 3'-UTR elements of various cytokine and proto
oncogene mRNAs detect distinct AUBPs within the same cell. When the in vivo
association of these proteins with AU-rich RNA was assessed using the combination
of in vivo UV-crosslinking and label transfer methods, we found that detachment
of monolayer cells by trypsinization or disruption of the microfilament network
by Cytochalasin treatment prior to UV light exposure, led to selective changes in
both the cytoplasmic distribution and in vivo RNA association of many AUBPs.
These data indicate that the organizational state of cytoarchitecture may
influence processes involved in AUBP-mediated mRNA metabolism.
PMID- 10197358
TI - The efficacy of paramagnetic ions on spin lattice relaxation time in biological
systems.
AB - This paper summarizes the observations of different studies concerning the
influence of paramagnetic ions on spin-lattice relaxation times. Neither the
comparison between different organs, different animals nor the comparison between
different tissues (normal and malignant) showed correlation of practical
consequences between the paramagnetic ion concentrations in whole tissues and
spin-lattice relaxation times.
PMID- 10197359
TI - Bone tissue changes in rats during prolonged restriction of motor activity.
AB - The objective of this investigation was to measure the effect of prolonged
restriction of motor activity (hypokinesia) of rats on the mass, density, mineral
composition, reconstruction parameters and elemental composition of their bone
tissue. The studies were done during 90 days of hypokinesia (HK) on 90 male
Wistar rats equally divided into two groups: (1) vivarium control rats (VCR) and
(2) hypokinetic rats (HKR). For the simulation of the hypokinetic effect the HKR
group was kept for 90 days in small individual cages made of wood that restricted
the movements of rats in all directions without hindering food and water intakes.
During the prehypokinetic period of 15 days and during the hypokinetic period of
90 days bone mass, bone density, bone calcium and phosphorus concentrations, bone
reconstruction parameters and elemental composition of bones were determined.
During the same periods food intake and body weight losses were also measured. In
the HKR group signs of osteoporosis in the spongy structures of the tubular bones
were observed; they also showed significant decrease in rat femur weight, and in
cross section of the rat femur, and in mineral concentrations of the femoral head
when compared with the VCR group. The HKR group also show a significant decrease
in food intake and body weight when compared with the VCR group. The
corresponding parameters did not change significantly in the VCR group when
compared with the baseline control values. It was concluded that prolonged
exposure to HK induced osteoporosis and structural changes in bones. This
apparently occurred due to inhibition of bone tissue formation in the HKR group.
PMID- 10197360
TI - Morphometric examination of glomerulus and juxta glomerural system of rat kidney
during prolonged restriction of motor activity.
AB - The aim of this study was to examine the structural changes of glomerular and
juxta glomerular system (JGS) of the kidney of rats during prolonged restriction
of motor activity (hypokinesia). The studies were performed during 90 days of
hypokinesia (HK) on 144 male Wistar rats divided into two groups: Group one
placed under ordinary vivarium conditions and serving as vivarium control rats
(VCR) and Group two subjected to HK and serving as hypokinetic rats (HKR). For
the simulation of the hypokinetic effect the HKR group was kept in small
individual cages made of wood that restricted the movements of rats in all
directions without hindering food and water intake. During a prehypokinetic
period of 15 days and the hypokinetic period of 90 days, body weight and food
intake were measured and morphometric examinations were done to measure the
cortical and juxta medullary glomerulus on kidney sections from the VCR and HKR
groups (eight rats from each group). Body weight and food intake decreased
significantly in the HKR groups when compared with the VCR group. Kidney weight
of rats increased, the superficial volume decreased and that of the juxta
medullary glomerules increased, whereas juxta glomerular granularity indexes
decreased significantly in the HKR group when compared with the VCR group. The
measured parameters did not change significantly in the VCR group when compared
with the baseline control values. It was concluded that prolonged exposure to HK
induces a significant increase in the kidney weight and a relationship appeared
between variations of the volume of cortical and juxta medullary glomerulus and
the function of the juxtaglomerular apparatus.
PMID- 10197361
TI - A hot/cool-system analysis of delay of gratification: dynamics of willpower.
AB - A 2-system framework is proposed for understanding the processes that enable--and
undermine--self-control or "willpower" as exemplified in the delay of
gratification paradigm. A cool, cognitive "know" system and a hot, emotional "go"
system are postulated. The cool system is cognitive, emotionally neutral,
contemplative, flexible, integrated, coherent, spatiotemporal, slow, episodic,
and strategic. It is the seat of self-regulation and self-control. The hot system
is the basis of emotionality, fears as well as passions--impulsive and reflexive-
initially controlled by innate releasing stimuli (and, thus, literally under
"stimulus control"): it is fundamental for emotional (classical) conditioning and
undermines efforts at self-control. The balance between the hot and cool systems
is determined by stress, developmental level, and the individual's self
regulatory dynamics. The interactions between these systems allow explanation of
findings on willpower from 3 decades of research.
PMID- 10197362
TI - The dynamics of operant conditioning.
AB - Existing models of operant learning are relatively insensitive to historical
properties of behavior and applicable to only limited data sets. This article
proposes a minimal set of principles based on short-term and long-term memory
mechanisms that can explain the major static and dynamic properties of operant
behavior in both single-choice and multiresponse situations. The critical
features of the theory are as follows: (a) The key property of conditioning is
assessment of the degree of association between responses and reinforcement and
between stimuli and reinforcement; (b) the contingent reinforcement is
represented by learning expectancy, which is the combined prediction of response
reinforcement and stimulus-reinforcement associations; (c) the operant response
is controlled by the interplay between facilitatory and suppressive variables
that integrate differences between expected (long-term) and experienced (short
term) events; and (d) very-long-term effects are encoded by a consolidated memory
that is sensitive to the entire reinforcement history. The model predicts the
major qualitative features of operant phenomena and then suggests an experimental
test of theoretical predictions about the joint effects of reinforcement
probability and amount of training on operant choice. We hypothesize that the set
of elementary principles that we propose may help resolve the long-standing
debate about the fundamental variables controlling operant conditioning.
PMID- 10197363
TI - Naive probability: a mental model theory of extensional reasoning.
AB - This article outlines a theory of naive probability. According to the theory,
individuals who are unfamiliar with the probability calculus can infer the
probabilities of events in an extensional way: They construct mental models of
what is true in the various possibilities. Each model represents an equiprobable
alternative unless individuals have beliefs to the contrary, in which case some
models will have higher probabilities than others. The probability of an event
depends on the proportion of models in which it occurs. The theory predicts
several phenomena of reasoning about absolute probabilities, including typical
biases. It correctly predicts certain cognitive illusions in inferences about
relative probabilities. It accommodates reasoning based on numerical premises,
and it explains how naive reasoners can infer posterior probabilities without
relying on Bayes's theorem. Finally, it dispels some common misconceptions of
probabilistic reasoning.
PMID- 10197364
TI - The comprehension and validation of social information.
AB - The information one acquires in daily life concerns specific people and events
about which one has prior knowledge. A theory of social cognition is proposed to
account for the comprehension and verification of such information. The theory
views comprehension as a process of constructing situation models of new
information on the basis of previously formed models about its referents. The
theory specifies the conditions in which statements about familiar people and
events (e.g., "Jane Fonda does aerobics") are spontaneously recognized as true or
false in the process of comprehending them. It further specifies the conditions
in which these spontaneous validity judgments of a statement will influence
perceptions of its implications when the statement is made in a social context.
The comprehension of both single statements and multiple pieces of information in
combination is considered.
PMID- 10197365
TI - Conjoint recognition.
AB - The process-dissociation model has stimulated important advances in the study of
dual-process conceptions of memory. The authors review some limiting properties
of that model and consider the degree of support for its parent theory (the
recollection-familiarity distinction). A 2nd-generation model (conjoint
recognition) is proposed that addresses these limitations and supplies additional
capabilities, such as goodness-of-fit tests, the ability to measure dual
processes for false-memory responses, and statistical procedures for testing
within- and between-conditions hypotheses about its parameters. The conjoint
recognition model also implements an alternative theoretical interpretation (the
identity-similarity distinction of fuzzy-trace theory). Worked applications to
data are provided.
PMID- 10197366
TI - Factors associated with the initiation and duration of breastfeeding: a review of
the literature.
AB - Breastfeeding is promoted internationally as the preferred method of feeding for
infants up to the age of four to six months. As a consequence there is much
research interest in factors which may be predictors of breastfeeding. This paper
presents a review of the recent literature identifying factors associated with
the initiation and duration of breastfeeding among Western women. Attention was
focused on studies which employed multivariate analysis of the data and
breastfeeding initiation and duration were considered as two uniquely separate
events. This review reveals that the associations between breastfeeding and many
of the factors commonly investigated were not consistent. Many of the strong
associations previously reported in univariate studies were not evident in more
recent studies which employed multivariate analysis to control for covariates and
potential confounders. While there was a strong and consistent association with
demographic factors such as maternal age and level of education, there was a less
consistent association with factors such as marital and socioeconomic status.
Similarly, the previously reported univariate associations between breastfeeding
and biomedical factors such as parity, method of delivery and infant health were
less consistent in multivariate studies. However, a consistent negative
association has been reported between maternal smoking habits and breastfeeding
duration. More recent studies have investigated the association between
breastfeeding and psychosocial factors. There is evidence to suggest that fathers
play an important role in the breastfeeding decision and that intended duration
is a strong predictor of actual duration. Despite the inconsistency of the
reported associations, this review highlights the fact that breastfeeding is
multifactorial in nature and future programs aimed at promoting breastfeeding
must take this into consideration.
PMID- 10197367
TI - Suitability of breastfeeding facilities outside the home: an audit of baby change
rooms in shopping centres.
AB - In an attempt to identify and audit breastfeeding facilities (baby care rooms)
outside the home, this study considered their presence and suitability for
breastfeeding in major shopping centres in a low socio-economic area. Only 48% of
the shopping centres had baby care rooms, all of which were located either in or
next to toilets and were indicated by a range of symbols and terms. The baby care
rooms were audited for breastfeeding suitability using the NMAA (Nursing Mothers'
Association of Australia) Baby Care Room criteria as an assessment procedure.
Only 43.7% of the baby care rooms met all of the 8 NMAA Baby Care Room criteria.
Reliability of this assessment process was moderate with a kappa of 0.52. In
reviewing these criteria, it was found that more specific clarification of some
of the criteria should be undertaken to improve the assessment process. Mothers
need to be reassured if they wish to breastfeed in public places by using baby
care rooms, that these rooms are suitable for breastfeeding. If breastfeeding is
to be encouraged, since it is a healthy choice, it needs to be an easy choice-
easy to do outside the home because there are suitable places to breastfeed.
PMID- 10197368
TI - Orofacial exercises for babies with breastfeeding problems?
AB - Young babies occasionally have aberrant orofacial movements that may appear to be
the cause of their breastfeeding difficulties. There has been a trend to treat
this by introducing corrective exercises for the affected muscle(s). Such
treatments have had their bases in therapeutic measures that were originally
designed for severely neurologically impaired babies. In fact, most babies with
breastfeeding problems are neurologically intact, with many needing only minimal
but specific interventions predominantly involving the gape response, attachment
and positioning. If the baby's gape response is poor, a minimal amount of breast
tissue is taken into the baby's mouth, and abnormal orofacial movements during
breastfeeds are the automatic result. This paper re-examines the use of orofacial
exercises--often called "suck training"--for babies with breastfeeding problems.
There can be negative results from using specific orofacial exercises in an
arbitrary or generalised manner. Precautions and guidelines for appropriate
corrective measures are discussed.
PMID- 10197369
TI - The Blue Mountains Breastfeeding Friendly Program.
PMID- 10197370
TI - Breasts, babies and universities--reflections of two lactating professors.
AB - This is a transcript of a presentation made by Mary E Black and Amanda Sinclair
at the "Winds of Change" conference in Sydney on July 12, 1998. This was an
international conference looking at issues around women in universities. It is
reprinted here as many of the issues are of relevance to the readers of this
journal. Both Mary and Amanda are experienced nursing mothers who also have high
profile careers and are strongly committed to their families. In a sense they are
pioneers as they speak openly about the conflicts both internal and external that
they encounter. They were both asked to fly to Sydney to present this paper but
decided not to, citing family responsibilities. Instead they persuaded the
conference organisers to fund them to produce a video, shot in both Cairns and
Melbourne and later edited into a presentation. This was shown to acclaim at the
conference and provoked a lively discussion. If organisations are creative, they
can do things differently and thus ensure that nursing mothers can fully
participate in professional life.
PMID- 10197371
TI - The treatment of tuberculosis in HIV-infected persons.
PMID- 10197372
TI - Longitudinal analysis of serum chemokine levels in the course of HIV-1 infection.
AB - OBJECTIVES: To investigate the correlation between the serum levels of the CC
chemokines RANTES, macrophage inflammatory protein (MIP)-1alpha and MIP-1beta,
and the progression of HIV-1 disease. DESIGN: Retrospective analysis of serial
serum samples from HIV-1 seroconverters selected according to clinical outcome.
METHODS: Twenty-one patients, derived from a cohort recruited between 1985 and
1996 for a prospective study of the natural history of HIV infection, were
analysed. All patients had at least one HIV-1-seronegative sample within 1 year
prior to the first seropositive test and were followed longitudinally throughout
the course of HIV-1 infection (mean follow-up, 73.5 months). Nine were rapid
progressors (RP; patients who developed AIDS within 60 months of antibody
seroconversion), seven were slow progressors (SP; patients who developed AIDS
after 60 months), and five were long-term asymptomatic (LTA; patients with
circulating CD4+ cells higher than 400 x 10(6)/l, no signs of HIV disease, no
antiretroviral therapy for more than 96 months). A total of 339 serum samples was
studied (mean, 16.1 per patient). The levels of RANTES, MIP-1alpha and MIP-1beta
were measured by enzyme-linked immunosorbent assay and correlated with different
immunological and clinical parameters. RESULTS: Over the entire follow-up period,
the geometric mean of serum RANTES was significantly higher in RP [68.6 ng/ml;
95% confidence interval (CI), 56.9-82.7] than in SP (23.7 ng/ml; 95% CI, 20.0
28.2; P < 0.001) and LTA (19.5 ng/ml; 95% CI, 15.5-24.5; P < 0.001). This
difference was already significant during the early clinical stages, when
patients had peripheral blood CD4+ cell counts still greater than 400 x 10(6)/l
(P < 0.001). By contrast, the mean serum levels of MIP-1alpha and MIP-1beta did
not differ significantly between the three study groups. Multivariate analysis
using the Cox proportional hazard model demonstrated that the mean serum
concentration of RANTES before the development of AIDS was independently
associated with the time to AIDS (relative risk, 4.5; 95% CI, 1.1-18.2; P =
0.035). In patients with low versus high mean serum RANTES before the fall of
CD4+ cells below 400 x 10(6)/l, the median AIDS-free time was 117.5 and 42.7
months, respectively (P = 0.037). CONCLUSION: These data suggest that an
elevation of serum RANTES predicts a rapid progression of the disease since the
early stages of HIV-1 infection.
PMID- 10197373
TI - Acute upregulation of CCR-5 expression by CD4+ T lymphocytes in HIV-infected
patients treated with interleukin-2. ANRS 048 IL-2 Study Group.
AB - BACKGROUND: The treatment of HIV-infected patients with interleukin (IL)-2 causes
a sustained increase in CD4+ T-lymphocyte counts, involving both naive and memory
cells. However, the short-term immunological effects of IL-2, which may shed
light on the mechanism of immune reconstitution by this cytokine, are unknown.
OBJECTIVE: To evaluate the acute effect of IL-2 on circulating T-lymphocyte
subpopulations and their expression of chemokine receptors. DESIGN AND METHODS:
Flow cytometry, reverse transcriptase polymerase chain reaction and chemokine
receptor function experiments were performed before and after 5 days of IL-2
administration in 30 HIV-infected patients. RESULTS: IL-2 induced an acute
lymphopenia of both naive and memory T-helper (TH) lymphocytes. This was
associated with a large increase in CC-chemokine receptor (CCR)-5 and CCR-2b
expression by TH cells. Before IL-2 treatment, CCR-5 was mostly produced by CD62L
memory TH lymphocytes. After 5 days of IL-2 administration, the level of CCR-5
mRNA in circulating cells was 18.6 times higher than before treatment (P <
0.002). CCR-5 expression was upregulated in CD62L- memory TH lymphocytes, but
also in CD62L+ memory and in naive (CD62L+ CD45RO-) TH lymphocytes. IL-2
treatment also increased the function of CCR-5 in TH cells. CONCLUSIONS:
Chemokine receptors are involved in trafficking of lymphocytes. The IL-2-induced
upregulation of chemokine receptors in TH cells may thus play a role in the acute
effects of this cytokine in TH lymphocyte redistribution.
PMID- 10197374
TI - Redistribution of body fat in HIV-infected women undergoing combined
antiretroviral therapy.
AB - OBJECTIVES: To investigate the prevalence, metabolic features and risk factors of
a particular pattern of fat redistribution (FR), characterized by a progressive
enlargement of breast and abdominal girth associated with a wasting of the lower
limbs, observed in HIV-infected women treated with combined antiretroviral (ARV)
therapy. DESIGN: Cross-sectional study. SETTING: Outpatients attending the
Institute of Infectious Diseases, University of Milan, Milan, Italy. PATIENTS AND
METHODS: HIV-infected women treated with two or more ARV drugs, observed between
December 1997 and February 1998. FR was confirmed by means of a physical
examination and dual-energy X-ray absorptiometry (DEXA). The metabolic and
endocrinological measurements in patients with FR were compared with those in FR
free women. RESULTS: FR was observed in 32 out of 306 women (10.5%). DEXA
revealed more trunk fat (P < 0.01) and less leg fat (P < 0.001) in the patients
with FR than in the matched controls. There were no significant differences in
laboratory test results between the two groups. All of the FR patients were
taking lamivudine-containing regimens; 20 of them were also taking a protease
inhibitor (PI). The association of FR with lamivudine-including regimens was
statistically significant (P = 0.017). Among the patients taking lamivudine, the
risk associated with treatments including PI was 1.8 (95% CI 0.8-3.8, P = 0.12).
A total duration of ARV therapy of more than 1000 days was associated with a
greater risk of developing FR (OR 10.8; 95% CI 1.4-80.5; P = 0.0207). Stepwise
logistic regression analyses indicated that prolonged ARV therapy and a viral
load of more than 10000 copies per ml at the beginning of the last ARV regimen
were the only variables that significantly and independently correlated with the
risk of FR. CONCLUSIONS: The observed body modifications are caused by a
redistribution of body fat without fat loss that is apparently not associated
with hyperlipidemia, altered glucose metabolism or other endocrinological
disorders. The development of FR in patients receiving only reverse transcriptase
(RT) inhibitors suggests the presence of a PI-independent mechanism that deserves
further investigation.
PMID- 10197375
TI - Urological complaints in relation to indinavir plasma concentrations in HIV
infected patients.
AB - OBJECTIVE: To assess the relationship between indinavir-associated urological
complaints and indinavir plasma concentrations. DESIGN: Case series, comparing
indinavir plasma concentrations in cases with average concentrations in a control
group. METHODS: Patients taking 800 mg indinavir three times a day (tid), who
presented with overt urological complaints (renal colic, flank pain or
haematuria) were selected for the study. Plasma indinavir concentrations were
measured by means of a standardized high performance liquid chromatography (HPLC)
method. Plasma samples taken at 1.5-8 h after the last indinavir ingestion were
included for evaluation. Results were compared with the full pharmacokinetic
curves of indinavir plasma concentrations from a control group of 14 patients
taking 800 mg indinavir tid without urological complaints, and were expressed as
concentration ratios. A ratio of 1 indicated a plasma concentration equalling the
average concentration in the control population at the same point in time after
the ingestion of indinavir. RESULTS: Seventeen patients (five women) were
enrolled and the indinavir concentrations of 15 patients could be evaluated.
Fourteen (93%) patients had a concentration above the mean of the controls, 12
(80%) patients had a concentration above the upper 95% confidence limit, and one
(7%) patient had a concentration below the lower 95% confidence limit. The mean
indinavir concentration in patients with urological complaints (ratio range 0.55
11.49) was significantly higher than the average concentration and the upper 95%
confidence limit of the control group (P < 0.05). The results could not be
explained by differences in weight, sex or drug interactions. Two patients had
chronic active hepatitis B infection. In six patients with indinavir
concentrations above the upper 95% limit, indinavir was reduced to 600 mg tid.
Upon repeat measurement after the dose adjustment, their indinavir plasma
concentrations fell within the 95% confidence interval around the mean of the
control population. All six patients remained asymptomatic and had viral loads of
less than 500 copies per ml after a follow-up of 5-16 months. CONCLUSIONS:
Urological complications occurring during indinavir treatment were associated
with elevated indinavir plasma concentrations in 80% of patients in this study.
Indinavir plasma concentrations should be monitored upon presentation of
urological complaints, on the basis of which dose reductions may be applied if
brief interruption and increased hydration are ineffective.
PMID- 10197376
TI - A phase I/II study of the safety and pharmacokinetics of nevirapine in HIV-1
infected pregnant Ugandan women and their neonates (HIVNET 006).
AB - OBJECTIVE: To determine the safety, pharmacokinetics, tolerance, antiretroviral
activity, and infant HIV infection status after giving a single dose of
nevirapine to HIV-1-infected pregnant women during labor and their newborns
during the first week of life. DESIGN: An open label phase I/II study. SETTING:
Tertiary care hospital, Kampala, Uganda. PATIENTS AND INTERVENTIONS: Nevirapine,
200 mg, was given as a single dose during labor to 21 HIV-1-infected pregnant
Ugandan women. In cohort 1, eight infants did not receive nevirapine whereas in
cohort 2, 13 infants received a single dose of nevirapine, 2 mg/kg, at 72 h of
age. OUTCOMES: The number and type of adverse events; nevirapine concentrations
in the plasma and breast milk; maternal plasma HIV-1 RNA copy number before and
up to 6 weeks after delivery; and HIV-1 infection status of the infants were
monitored. RESULTS: Nevirapine was well tolerated by women and infants; no
serious adverse events that were related to nevirapine were observed. Median
nevirapine concentration in the women at delivery was 1623 ng/ml (range 238-2356
ng/ml); median cord/maternal blood ratio of 0.75 (0.37-0.93). The median half
life in women was 61.3 h (27-90 h) and the transplacental nevirapine half-life in
infants who did not receive a neonatal dose was 54 h. The median half-life after
a single dose at 72 h in infants was 46.5 h. During the first week of life, the
median colostrum/breast milk to maternal plasma nevirapine concentration was
60.5% (25-122%). The median nevirapine concentration in breast milk 1 week after
delivery was 103 ng/ml (25-309 ng/ml). Plasma nevirapine concentrations were
above 100 ng/ml in all infants from both cohorts tested at age 7 days. Maternal
HIV-1 RNA levels decreased by a median of 1.3 logs at 1 week postpartum, and
returned to baseline by 6 weeks postpartum. Detectable plasma HIV-1 RNA was
observed in one out of 22 (4.5%) infants at birth; three out of 21 (14%) at 6
weeks; and four out of 21 (19%) at 6 months of age. CONCLUSION: The
administration of a single dose of nevirapine to women during labor and to their
newborns at 72 h was well tolerated and showed potent antiretroviral activity in
the women at 1 week after dosing without rebound above baseline 6 weeks after a
single dose. The nevirapine concentration was maintained above the target of 100
ng/ml in infants at age 7 days, even in those infants not receiving a neonatal
dose. This regimen has promise as prophylaxis against intrapartum and early
breast milk transmission in a breastfeeding population.
PMID- 10197377
TI - The effect of Plasmodium falciparum malaria on HIV-1 RNA blood plasma
concentration.
AB - OBJECTIVES: This study was undertaken to determine the relative effect of malaria
infection on HIV concentration in blood plasma, and prospectively to monitor
viral concentrations after antimalarial therapy. DESIGN: A prospective, double
cohort study was designed to compare the blood HIV-1 RNA concentrations of HIV
positive individuals with and without acute malaria illness. Subjects were
followed for 4 weeks after successful malaria therapy, or for 4 weeks from
enrollment (controls). METHODS: Malawian adults with symptomatic Plasmodium
falciparum parasitemia (malaria group) and asymptomatic, aparasitemic blood
donors (control group) were tested for HIV-1 antibodies to identify appropriate
study groups. The malaria group received antimalarial chemotherapy only and were
followed with sequential blood films. In both groups, blood plasma HIV-1 RNA
viral concentrations were determined at enrollment and again at 1, 2 and 4 weeks.
RESULTS: Forty-seven malaria patients and 42 blood donors were enrolled. At
enrollment blood plasma HIV-1 RNA concentrations were approximately sevenfold
higher in patients with malaria than in blood donors (medians 15.1 x 10(4) and
2.24 x 10(4) copies/ml, respectively, P = 0.0001). No significant changes in
median HIV-1 concentrations occurred in the 21 blood donors followed to week 4 (P
= 0.68). In the 27 subjects successfully treated for malaria who were followed to
week 4, a reduction in plasma HIV-1 RNA was observed from a median of 19.1 x
10(4) RNA copies/ml at enrollment, to 12.0 x 10(4) copies/ml at week 4, (P =
0.02). Plasma HIV-1 concentrations remained higher in malaria patients than
controls (median 12.0 x 10(4) compared with 4.17 x 10(4) copies/ml, P = 0.086).
CONCLUSIONS: HIV-1 blood viral burden is higher in patients with P. falciparum
malaria than in controls and this viral burden can, in some patients, be partly
reduced with antimalarial therapy.
PMID- 10197378
TI - Micronutrient supplementation in the AIDS diarrhoea-wasting syndrome in Zambia: a
randomized controlled trial.
AB - OBJECTIVE: As HIV has spread through sub-Saharan Africa, persistent diarrhoea has
emerged as a major problem in hospitals and in the community in severely affected
areas. We have previously demonstrated that antiprotozoal therapy with
albendazole reduces diarrhoea in AIDS patients in urban Zambia. This trial was
designed to test the hypothesis that the clinical response to albendazole might
be improved by oral micronutrient supplementation. DESIGN: Randomized, placebo
controlled trial. SETTING: Home care service of Ndola Central Hospital, Zambia.
PATIENTS: HIV-seropositive patients with persistent diarrhoea. INTERVENTION:
Patients were randomized to albendazole plus vitamins A, C and E, selenium and
zinc orally or albendazole plus placebo, for 2 weeks. MAIN OUTCOME MEASURES: Time
with diarrhoea following completion of treatment; mortality; adverse events.
RESULTS: Serum vitamin A and E concentrations before treatment were powerful
predictors of early mortality, but supplementation did not reduce time with
diarrhoea or mortality during the first month, even after taking into account
initial vitamin A or E concentrations, CD4 cell count or clinical markers of
illness severity. Serum concentrations of vitamins A and E did not increase
significantly in supplemented patients compared with those given placebo, and
there were no changes in CD4 cell count or haematological parameters. No adverse
events were detected except those attributable to underlying disease.
CONCLUSIONS: Although micronutrient deficiency is predictive of early death in
Zambian patients with the diarrhoea-wasting syndrome, short-term oral
supplementation does not overcome it nor influence morbidity or mortality.
PMID- 10197379
TI - Isoniazid prophylaxis for tuberculosis in HIV infection: a meta-analysis of
randomized controlled trials.
AB - OBJECTIVES: To evaluate the efficacy of isoniazid for the prevention of
tuberculosis in tuberculin skin test-positive and negative individuals with HIV
infection. DESIGN: Meta-analysis of randomized controlled trials. SETTING: Seven
trials from Mexico, Haiti, the United States, Zambia, Uganda and Kenya. PATIENTS:
Individuals free from tuberculosis, 2367 persons in the intervention and 2162 in
the control groups. INTERVENTION: Comparison of isoniazid with placebo or no
prophylaxis. METHODS: A systematic search of the literature was carried out from
1985 to October 1997 for randomized controlled trials of isoniazid prophylaxis in
HIV-infected persons. Two reviewers evaluated the relevance of each candidate
study and the validity of eligible trials. Studies were pooled using a random
effect model, conducting secondary analyses for tuberculin skin test-positive and
negative persons. RESULTS: Mean follow-up in trials varied between 0.4 and 3.2
years. Pooling all seven trials, a risk ratio was found for persons treated with
isoniazid for developing tuberculosis of 0.58 [95% confidence interval (CI), 0.43
0.80] and 0.94 (95% CI, 0.83-1.07) for death. In groups of tuberculin skin test
positive and negative persons, the risk ratio of tuberculosis was 0.40 (95% CI,
0.24-0.65) and 0.84 (95% CI, 0.54-1.30), respectively, and the difference in the
effectiveness of isoniazid versus placebo between these groups was statistically
significant (P = 0.03, for the difference of summary estimates). Consistency of
results was found across trials (P > 0.10, heterogeneity value) for all
comparisons. CONCLUSIONS: Prophylaxis with isoniazid reduces the risk of
tuberculosis in persons with HIV infection. The effect is restricted to
tuberculin skin test-positive persons.
PMID- 10197380
TI - HIV-1 seroprevalence among childbearing women in northern Thailand: monitoring a
rapidly evolving epidemic.
AB - OBJECTIVES: To describe trends in prevalence of HIV-1 infection among women
giving birth at Chiang Rai Hospital (CRH) and to assess risk factors associated
with HIV infection in this population. DESIGN: Analysis of hospital registry data
for all deliveries at CRH from 1990 to mid-1997. METHODS: From 1990 to mid-1997,
women giving birth at CRH were tested for HIV-1 infection using enzyme
immunoassay (EIA); positive sera were confirmed using a different manufacturer's
EIA. Demographic and clinical data were abstracted from delivery-ward log books.
RESULTS: Data from 40723 deliveries indicated that overall HIV-1 seroprevalence
increased sharply, from 1.3% in 1990 to a peak of 6.4% in 1994, and then declined
to 4.6% in the first 6 months of 1997. Prevalence was highest, at 7.0%, among
young (age < or = 24 years) primigravidas, compared with 2.4% among older (age >
or = 25 years) multigravidas. When we controlled for age, prevalence declined 40%
from 1994 to 1997 among young primigravidas (95% confidence interval for
percentage reduction, 16-57). Amongst older multigravid women, prevalence was
consistently lower but increased steadily from 2.7% in 1994 to 3.4% in 1997.
CONCLUSIONS: A rapid rise in HIV prevalence in childbearing women was followed by
a sharp decline among young primigravidas. In each year, the prevalence was
highest among young primigravidas. They may be the best subgroup of pregnant
women for monitoring HIV epidemic trends, but they also represent a challenging
prevention priority that will require its own targeted interventions.
PMID- 10197381
TI - Impaired fertility in HIV-1-infected pregnant women: a clinic-based survey in
Abidjan, Cote d'Ivoire, 1997.
AB - OBJECTIVE: Differences in fertility among HIV-1-positive and HIV-negative women
tested in prenatal clinics were suspected by routine data collection in Abidjan,
Cote d'Ivoire. This study was conducted on detailed fertility patterns among
women at the same antenatal care centres, in order to assess these differences.
METHOD: The survey was carried out on 1201 consecutive women who agreed to be
tested for HIV. Data collected included a detailed account of pregnancies, the
time interval between the last two pregnancies, and the health status at the time
of the survey. Blood samples were tested for HIV and syphilis with informed
consent. RESULTS: Despite an earlier exposure to pregnancy risk, HIV-1-infected
women aged 25 years and above, had, on the average, fewer pregnancies than
uninfected women. An analysis of the interval between the last two pregnancies
among multigravidae showed that, all things being equal, being HIV-1 positive
decreased the risk of being pregnant by 17% (Cox regression, hazard ratio = 0.83,
95% confidence interval (CI): 0.69-0.99). This shift in the occurrence of the
last pregnancy was more profound among HIV-1-positive women already at the
symptomatic or AIDS stage, than among asymptomatic women. CONCLUSION: These data
confirm that women infected by HIV-1 would become pregnant less often than
uninfected women, for an equal exposure to the risk of pregnancy. Therefore HIV-1
positive women could be under-represented at antenatal centres. Programmes
involving such settings both for epidemiological surveillance and the reduction
of mother-to-child transmission should take this observation into account.
PMID- 10197382
TI - Hepatitis C virus (HCV) genotype does not appear to be a significant prognostic
factor in HIV-HCV-coinfected patients.
PMID- 10197383
TI - Incidence of rash and discontinuation of nevirapine using two different
escalating initial doses.
PMID- 10197384
TI - Patterns of response (CD4 cell count and viral load) at 6 months in HIV-infected
patients on highly active antiretroviral therapy.
PMID- 10197385
TI - Estimation of HIV-1 prevalence in the population of Abidjan by adjustment of the
prevalence observed in antenatal centres.
PMID- 10197386
TI - Interleukin-2 treatment of microglia has no effect on in vitro HIV infection.
PMID- 10197387
TI - HIV-1 infection in a heterosexual man homozygous for CCR-5 delta32.
PMID- 10197388
TI - Visual loss due to cryptococcal meningitis in AIDS patients.
PMID- 10197389
TI - V3-loop and nef gene sequences of HIV-1 isolates from a hemophiliac cohort with
long-term non-progressive infection.
PMID- 10197390
TI - Pneumocystosis versus pulmonary Pneumocystis carinii colonization in HIV-negative
and HIV-positive patients.
PMID- 10197391
TI - Genital herpes simplex virus type 2 shedding is increased in HIV-infected women
in Africa.
PMID- 10197392
TI - The definitions and epidemiology of pleural space infection.
AB - Infections of the pleural space are caused by a diverse group of clinical
conditions that include trauma, post-operative states, and pneumonia. Although
pleural effusions accompany bacterial pneumonia in up to 60% of patients, they
uncommonly influence management because the effusion in most patients disappears
with antibiotic administration. Unfortunately, the large number of patients with
pneumonia provide an abundant supply of patients who fail to respond to
antibiotic administration alone and subsequently present with pleural fluid
loculation, pleural sepsis, or empyema. This article provides an overview of the
classification schemes that have been used to characterize pleural space
infections and highlight the epidemiology of those patients who present with
complicated parapneumonic effusions and empyema.
PMID- 10197393
TI - Pathophysiology of pleural space infections.
AB - The pleura responds to the presence of infecting organisms with a vigorous
inflammatory response associated with an exudation of white blood cells and
proteins. Changes in pleural permeability lead to formation of an exudative
pleural effusion. The pleural mesothelial cell is the primary cell lining the
pleural space and, when activated by the presence of organisms, initiates the
inflammatory response by releasing a battery of chemokines and cytokines.
Mesothelial cells are actively phagocytic and also release oxidants and
proteases. The acute inflammatory process may resolve with appropriate antibiotic
therapy and drainage leaving minimal fibrosis. However, under certain
circumstances vigorous pleural fibrosis with scarring and loss of delineation of
pleural surfaces can occur. Recognition of the stage of development of the
empyema is an important clinical judgement that can affect outcome. The
pathogenesis of infections of the pleural space and the role played by the
various cell types is delineated in this article.
PMID- 10197394
TI - Pleural space infections: microbiology and antimicrobial therapy.
AB - Although most recognized pleural space infections are caused by Staphylococcus
aureus, Streptococcus pneumoniae, enteric gram-negative bacilli, or anaerobic
bacteria, the spectrum of possible pathogens is broad and includes fungi and even
protozoa, reflecting the mixed origins of these infections. When pleural space
infection is suspected, a diagnostic thoracocentesis is indicated. An immediate
gram-stained smear of directly aspirated pleural fluid often can guide the
physician's initial treatment. After recovery of the pathogens, optimal
antibiotic therapy should be based on standardized susceptibility testing and
consensus guidelines. Antibiotic therapy alone may be curative, but adequate
drainage must also be achieved in most cases.
PMID- 10197395
TI - Imaging techniques for pleural space infections.
AB - Radiology plays a central role in the evaluation and management of pleural space
infections. Conventional radiographs, including decubitus films, remain the
primary radiological study in the detection of parapneumonic pleural effusions.
Loculated collections develop as a result of visceral-to-parietal pleural
adhesions and appear radiographically as longitudinally oriented, lenticular
shaped opacities. Contrast-enhanced computed tomography scans accurately
distinguish lung abscess from loculated empyema and provide a global view of the
extent and complexity of the pleural collection. Sonography allows portable
bedside examination of critically ill patients and is useful in the detection and
sampling of small effusions. Real-time ultrasound evaluation of pleural
collections accurately determines the size and nature of the effusion and may be
useful in predicting the success of thoracentesis. As cross-sectional studies are
obtained in the majority of patients with complex pleural space infection and
provide valuable information, the precise clinical utility of computed tomography
scans and ultrasound in these patients remains undetermined.
PMID- 10197396
TI - Utility of fibrinolytic agents for draining intrapleural infections.
AB - Multiple studies have shown that the intrapleural instillation of fibrinolytic
agents provides an effective and safe mode of treatment for complicated
parapneumonic effusions and empyemas that decrease the need for surgical
interventions. Although most investigators use streptokinase and urokinase, the
technique of instillation is not standardized. The usual dose of streptokinase is
250,000 IU, but doses range from 50,000 to 220,000 IU for urokinase. Reported
success rates range from 38% to 100%, but outcomes depend on the stage of
progression of the parapneumonic effusion when fibrinolytics are employed.
Fibrinolytics are more effective in complicated parapneumonic effusions than in
established empyemas. Although complications of fibrinolytic therapy rarely
occur, they result most often from allergic reactions to streptokinase. Urokinase
is safer but more expensive. More randomized, comparative, controlled studies are
needed to further define the most effective mode of fibrinolytic therapy for
subgroups of patients with pleural infection.
PMID- 10197397
TI - Indications for draining a parapneumonic effusion: an evidence-based approach.
AB - A patient with pneumonia who develops a parapneumonic effusion challenges the
physician to determine the need for pleural fluid drainage. This determination is
influenced by multiple factors including the patient's general state of health,
the existence of comorbidities, the virulence of the underlying pathogen, and the
extent of the pneumonia that dictate clinical outcome and the relative risks and
benefits of drainage. The presence of intrapleural pus represents the only factor
that clearly establishes the need for drainage, although most experts recommend
draining pleural fluid that is positive by Gram's stain or culture for a
pathogen. Other factors such as the extent of the patient's pneumonia, severity
of systemic signs of inflammation, radiographic features of the effusion, and
pleural fluid chemical profile assist clinical decision making. The fundamental
principle that guides therapy is the need to promptly and effectively drain
pleural fluid whenever it appears likely that it will progress to a frank empyema
with antibiotic therapy alone.
PMID- 10197398
TI - Image-guided drainage techniques.
AB - The basic principles of empyema management center on the initiation of
antibiotics and effective pleural space drainage. For patients with empyemas in
the exudative or fibrinopurulent stage, image-guided chest tubes have markedly
improved patient care. These catheters can be placed into ideal positions within
the chest by the use of various imaging techniques to promote effective drainage.
Because of a minimal need for tissue dissection, patients tolerate image-guided
catheters well with only local anesthetics. Multiple techniques exist to augment
tube drainage if necessary. Available approaches include tube exchange with
placement of a larger-caliber catheter, tube manipulation, and fibrinolytic
therapy. However, success of image-guided catheters depends on proper patient
selection, the skills of the operator, and the ability to monitor daily chest
tube function to ensure adequacy of drainage. Open surgical procedures can be
avoided in most treated patients.
PMID- 10197399
TI - Surgical management of intrapleural infections.
AB - Most patients with empyema require surgical intervention. Selection of therapy is
based on the patient's overall condition, on the cause of the empyema, and on the
stage of empyema progression. Parapneumonic effusions in the exudative or early
fibrinopurulent stage may be responsive to tube thoracostomy and may not require
further intervention in 65% of patients. More complicated parapneumonic effusions
require thoracoscopic or open thoracotomy for debridement or decortication and
are successfully managed in over 95% of patients. Empyemas that develop
postoperatively are more challenging to diagnose and treat. Open thoracotomy is
usually necessary unless patients are too ill to tolerate major surgery, in which
case simple open drainage is an alternative. Closure of any bronchopleural
fistula is necessary before an empyema can be eradicated. In patients with
empyema associated with an extrapulmonary infectious process, control of the
primary source of infection is required before definitive therapy of the empyema
is undertaken. The overall success rate of therapy for empyema is greater than
90% and the associated mortality rate is about 8%.
PMID- 10197400
TI - Tuberculous empyema.
AB - Tuberculous empyema represents a chronic, active infection of the pleural space
that contains a large number of tubercle bacilli. It is rare compared with
tuberculous pleural effusions that result from an exaggerated inflammatory
response to a localized paucibacillary pleural infection with tuberculosis. The
inflammatory process may be present for years with a paucity of clinical
symptoms. Patients often come to clinical attention at the time of a routine
chest radiograph or after the development of bronchopleural fistula or empyema
necessitatis. The diagnosis of tuberculous empyema is suspected on computed
tomography imaging by finding a thick, calcific pleural rind and rib thickening
surrounding loculated pleural fluid. The pleural fluid is grossly purulent and
smear positive for acid-fast bacilli. Treatment consists of pleural space
drainage and antituberculous chemotherapy. Problematic treatment issues include
the inability to re-expand the trapped lung and difficulty in achieving
therapeutic drug levels in pleural fluid, which can lead to drug resistance.
Surgery, which is often challenging, should be undertaken by experienced thoracic
surgeons.
PMID- 10197401
TI - A 60-year-old man with a left upper lobe mass and hemoptysis.
PMID- 10197402
TI - Treatment of young children's bedtime refusal and nighttime wakings: a comparison
of "standard" and graduated ignoring procedures.
AB - Young children with sleep problems received either "standard" or graduated
ignoring treatment. Both brief treatments were superior to a wait-list control
condition and resulted in comparable improvements in bedtime and nighttime sleep
problems. At bedtime, the treatments did not differ with respect to maternal
compliance and stress. For nighttime wakings, mothers in the graduated ignoring
group reported higher rates of compliance and less treatment-related stress.
Maternal characteristics predicted treatment outcome in the standard ignoring
condition. Following treatment, only positive side effects were observed. When
compared to the wait-list group, mothers in the standard ignoring group reported
less verbose discipline and decreased stress in parenting, while mothers in the
graduated ignoring group reported improved parent-child relationships. Treatment
gains were maintained over a 2-month follow-up period.
PMID- 10197403
TI - Comparing the Strengths and Difficulties Questionnaire and the Child Behavior
Checklist: is small beautiful?
AB - The Strengths and Difficulties Questionnaire (SDQ) is a brief behavioral
screening questionnaire that can be completed in 5 minutes by the parents or
teachers of children aged 4 to 16; there is a self-report version for 11- to 16
year-olds. In this study, mothers completed the SDQ and the Child Behavior
Checklist (CBCL) on 132 children aged 4 through 7 and drawn from psychiatric and
dental clinics. Scores from the SDQ and CBCL were highly correlated and equally
able to discriminate psychiatric from dental cases. As judged against a
semistructured interview, the SDQ was significantly better than the CBCL at
detecting inattention and hyperactivity, and at least as good at detecting
internalizing and externalizing problems. Mothers of low-risk children were twice
as likely to prefer the SDQ.
PMID- 10197404
TI - Heart rate variability and sustained attention in ADHD children.
AB - The major goal of the current study was to investigate the association between
continuous performance tests (CPTs) and the heart rate variability (HRV) of
attention deficit hyperactivity disorder (ADHD) children. The HRV, specifically
the 0.10-Hz component, may be considered to be a psychophysiological index of
effort allocation (motivation): The less effort the subject allocates, the
greater the 0.10-Hz component. Results indicated that, compared to controls, ADHD
subjects had a greater 0.10-Hz component, which was associated with poor test
performance over time. Thus, using a psychophysiological measure, we were able to
confirm the clinical concept of ADHD from a motivational perspective.
PMID- 10197405
TI - Exploratory eye movements to pictures in childhood-onset schizophrenia and
attention-deficit/hyperactivity disorder (ADHD).
AB - We investigated exploratory eye movements to thematic pictures in schizophrenic,
attention-deficit/hyperactivity disorder (ADHD), and normal children. For each
picture, children were asked three questions varying in amount of structure. We
tested if schizophrenic children would stare or scan extensively and if their
scan patterns were differentially affected by the question. Time spent viewing
relevant and irrelevant regions, fixation duration (an estimate of processing
rate), and distance between fixations (an estimate of breadth of attention) were
measured. ADHD children showed a trend toward shorter fixations than normals on
the question requiring the most detailed analysis. Schizophrenic children looked
at fewer relevant, but not more irrelevant, regions than normals. They showed a
tendency to stare more when asked to decide what was happening but not when asked
to attend to specific regions. Thus, lower levels of visual attention (e.g.,
basic control of eye movements) were intact in schizophrenic children. In
contrast, they had difficulty with top-down control of selective attention in the
service of self-guided behavior.
PMID- 10197406
TI - A two-year longitudinal study of neuropsychological and cognitive performance in
relation to behavioral problems and competencies in elementary school children.
AB - Despite interest in early neuropsychological status as a possible contributor to
children's behavioral development, prospective longitudinal investigations of
neuropsychological measures in relation to later behavioral outcomes in childhood
are few. A 2-year longitudinal study in a nonselected childhood sample is
reported. The study tested the influence of early neuropsychological performance
(verbal fluency, mental inhibitory control, and visual spatial ability) on later
childhood behavioral problems and social competency. Regular education children
(n = 235) were assessed at three time points 1 year apart. To control for
autocorrelation of outcome measures, Time 1 behavior was partialed while testing
the effects of Time 1 neuropsychological scores on Time 3 outcome. To control for
autocorrelation of neuropsychological scores, Time 2 scores were partialed while
testing the predictive effect of Time 1 scores on Time 3 outcome. Both sets of
regression models suggested modest but statistically significant effects for
inhibitory control and verbal fluency, but not IQ, reading, or visual spatial
ability, on behavioral outcome. Study results are consistent with a modest causal
effect of selected neuropsychological skills on later behavioral adjustment. The
findings support theories that implicate subtle neuropsychological dysfunction in
the development of behavioral problems in childhood.
PMID- 10197407
TI - The relation of child sexual abuse and depression in young women: comparisons
across four ethnic groups.
AB - To investigate the relation of child sexual abuse to depression and whether this
relation differed by ethnicity (African Americans, Mexican Americans, Native
Americans, and non-Hispanic whites), we surveyed 2,003 women between 18 and 22
years of age about family histories, sexual abuse, and depression. Reported rates
of child sexual abuse were similar across ethnic groups; approximately one-third
of each group reported some form of sexual abuse and about one-fifth of each
ethnic group reported experiencing rape. After controlling for background
characteristics identified as risk factors for both child sexual abuse and
depression, severity of child sexual abuse was significantly related to
depressive symptoms only for non-Hispanic whites and Mexican Americans. Child
sexual abuse variables accounted for more variance in depression than background
variables only for Mexican American women. Child physical abuse was the strongest
predictor of adult depression and the only significant predictor for each ethnic
group.
PMID- 10197408
TI - A test of interpersonal theory of depression in youth psychiatric inpatients.
AB - Coyne's (1976b) interpersonal theory of depression postulated that the
combination of depressive symptoms and excessive reassurance-seeking leads to
interpersonal problems (e.g., loneliness, devaluation). The present study is one
of the first to test this model among youth, particularly a clinical sample of
youth. Sixty-eight youth psychiatric inpatients (35 girls; 33 boys; mean age =
13.34 years, SD = 2.50) completed self-report measures of excessive reassurance
seeking, depressive symptoms, and interpersonal rejection. Results conformed to
the hypothesis: The statistical interaction of excessive reassurance-seeking and
depressive symptoms predicted interpersonal rejection, such that high-reassurance
seeking youth with depressive symptoms reported the most interpersonal rejection.
Implications of the findings for interpersonal theory of depression in youngsters
are discussed.
PMID- 10197409
TI - Childhood peer relationship problems and psychosocial adjustment in late
adolescence.
AB - Using prospective longitudinal data from the Christchurch Health and Development
Study, this paper examined the relationship between teacher reported peer
relationship problems at age 9 and psychosocial adjustment in late adolescence.
Results showed that, by age 18, children with high rates of early peer
relationship problems were at increased risk of externalizing behavior problems
such as criminal offending and substance abuse, but were not at increased risk of
anxiety disorder or major depression. Subsequent analyses revealed that these
associations were largely explained by the effects of child and family factors
associated with both early peer relationship problems and later adjustment. The
most influential variable in explaining associations between peer relationship
problems and later adjustment was the extent of children's early conduct
problems. These results suggest that reported associations between early peer
problems and later adjustment are noncausal, and appear to reflect underlying
continuities in behavioral adjustment.
PMID- 10197410
TI - Synthesis and hypolipidaemic evaluation of a series of alpha-asarone analogues
related to clofibrate in mice.
AB - A series of alpha-asarone analogues related to clofibrate, containing an acetic
acid group at C-2 of the aromatic ring, has been prepared as the acids or as the
ethyl and methyl esters. The corresponding alcohols were also synthesized by
reduction of the ethyl esters. The compounds were examined in hyperlipidaemic
male mice to evaluate their ability to modify serum lipoprotein cholesterol, low
density lipoprotein cholesterol, high-density lipoprotein cholesterol and
triglycerides after oral administration of 40 and 80 mg kg(-1) for 6 days. Except
for methyl 2-methoxy-5-nitro-4-(2-propenyl)phenoxyacetate at either dose, these
clofibrate-related phenoxyacetic acid derivatives were found to have significant
hypocholesterolaemic activity. Levels of low-density lipoprotein cholesterol and
triglycerides were significantly reduced and those of high-density lipoprotein
cholesterol were elevated. 2-Methoxy-5-nitro-4-(2-propenyl)phenoxyacetic acid was
active at both doses in all the tests. Clofibrate (150 mg kg(-1)) was more potent
at reducing low-density lipoprotein cholesterol. No activity was detected for the
alcohol derivatives. These preliminary results suggest that this class of
compound might have more promise as potential hypolipidaemic agents than other
alpha-asarone derivatives. Further investigation and characterization should be
performed to determine the mode of action of these agents on lipid metabolism.
PMID- 10197411
TI - Autocatalytic degradation and stability of obidoxime.
AB - The degradation of obidoxime chloride (toxogonin), a reactivator of inhibited
cholinesterase in organophosphorus poisoning, in concentrated (250 mg mL(-1))
acidic solutions was studied by HPLC at several temperatures to determine the
degradation mechanism. The degradation had an autocatalytic profile, which was
found to result from the formation of formaldehyde during the degradation
process. The activation energy of the hydrolysis was 26.2 kcal mol(-1). The shelf
life (t90, the time by which 10% of the drug has degraded) at 25 degrees C was
calculated by several methods and found to be more than 37 years. Autocatalysis,
a mechanism found only rarely in the degradation of pharmaceuticals, has not been
reported in previous studies of obidoxime hydrolysis.
PMID- 10197412
TI - In-vivo evaluation of indium-111-diethylenetriaminepentaacetic acid-labelling for
determining the sites and rates of protein catabolism in mice.
AB - Pharmacokinetic analyses of protein pharmaceuticals are of prime importance for
their clinical application. Because many proteins have pharmacological activity
at low concentrations, radiolabelling of proteins is widely used to identify the
sites and determine the rates of protein catabolism in-vivo due to the high
sensitivity of detection of radioactivity. Recently, a metallic radionuclide,
(111)In, has been used to trace the pharmacokinetics of proteins of interest
after conjugation of the proteins with diethylenetriaminepentaacetic acid (DTPA).
In this study, galactosyl-neoglycoalbumin (NGA) was reacted with the cyclic
dianhydride of DTPA and labelled with (111)In to estimate the validity of this
radiolabelling procedure for pharmacokinetic analyses. For comparison, we also
evaluated direct radioiodination, because directly-radioiodinated proteins are
widely used to assess the pharmacokinetics of proteins of interest. The hepatic
radioactivity profile after intravenous injection of [131I]NGA or [(111)In]DTPA
NGA into mice was analysed pharmacokinetically, and the first-order rate constant
representing the elimination of the respective radiometabolite from hepatic
parenchymal cells was determined. The results indicated that direct
radioiodination is inappropriate for pursuing the pharmacokinetics of the
proteins, because of rapid elimination of the radioactivity from the sites of
protein catabolism. These findings also implied that the [(111)In]DTPA label
could be used to identify the catabolic sites and determine the rates of
catabolism of proteins with relatively short biological half-lives, although
characterization of radiolabelled species at the sites of accumulation would be
required for accurate determination of the catabolic sites of proteins.
PMID- 10197413
TI - Resistance to glutathione depletion in diabetic and non-diabetic human
erythrocytes in-vitro.
AB - We have investigated the resistance of erythrocytes from diabetics and non
diabetics to glutathione depletion caused by p-benzoquinone, 1-chloro-2,4
dinitrobenzene (CDNB), diethyl maleate and 4-aminophenol. Incubation of
erythrocytes with 4-aminophenol (2 mM) caused a precipitous reduction (>80%) in
cellular glutathione levels although there was no significant difference between
4-aminophenol-mediated glutathione depletion in the diabetic and non-diabetic
cells. p-Benzoquinone and CDNB were both associated with a less severe initial
reduction in glutathione levels (>50% at 30 min) although p-benzoquinone caused
greater depletion (P < 0.001) at 4.5 h (21.1 +/- 3.1%, non-diabetic; 20.0 +/-
1.0%, diabetic) compared with CDNB (49.2 +/- 2.2%, non-diabetic; 51.3 +/- 1.1%
diabetic). Although there was no significant difference between the two types of
cell in terms of level of depletion, administration of diethyl maleate caused a
significant reduction in glutathione levels at 30 min (P < 0.0005), 3.5 h (P <
0.05) and 4.5 h (P < 0.05) in erythrocytes from diabetic man compared with those
from non-diabetic man. Co-administration of buthionine sulphoximine (20 mM) and 4
aminophenol (1 mM) also led to a significant reduction in glutathione levels in
diabetic cells at 30 min (P < 0.05), 3.5 h (P < 0.02) and 4.5 h (P < 0.007)
compared with those in non-diabetic cells. The observations that diabetic red
cells' resistance to depletion was similar to that of nondiabetic cells for three
of the four depletors, and that the combination of 4-aminophenol and buthionine
sulphoximine-mediated inhibition of glutathione synthesis was required to
illustrate differences suggests that diabetic complications might be a result of
the long-term effect of small deficiencies in oxidative self-defence mechanisms
such as glutathione.
PMID- 10197414
TI - Simultaneous use of sodium deoxycholate and dipotassium glycyrrhizinate enhances
the cellular transport of poorly absorbed compounds across Caco-2 cell
monolayers.
AB - The absorption-enhancing effect of a combination of sodium deoxycholate and
dipotassium glycyrrhizinate in Caco-2 cell monolayers has been compared with that
of the enhancers when used alone, and the mechanism of the enhancement was
partially elucidated. The effect of the combined compounds was evaluated by
measurement of transepithelial electrical resistance (TEER) and the cellular
permeability of the water-soluble model compounds sodium fluorescein (MW 376.3)
and fluorescein isothiocyanate dextran (MW 4400). The TEER of the monolayers
decreased with increasing concentrations of dipotassium glycyrrhizinate in
combination with 0.02% (w/v) sodium deoxycholate for 20 min, and reached a
minimum at 1% (w/v) dipotassium glycyrrhizinate. Although a combination of 0.02%
(w/v) sodium deoxycholate and 1% (w/v) dipotassium glycyrrhizinate enhanced the
cellular permeability of sodium fluorescein and fluorescein isothiocyanate
dextran, 0.02% (w/v) sodium deoxycholate and 1% (w/v) dipotassium glycyrrhizinate
alone had no effect on either the TEER of the monolayers or the cellular
transport of the water-soluble compounds. Sequential and separate exposure of the
monolayers to each enhancer for 10 min had no effect on the TEER, but a marked
decrease in TEER was observed when both compounds were used in combination. The
enhancing effect of the combination of sodium deoxycholate and dipotassium
glycyrrhizinate was inhibited by H7, a protein kinase C (PKC) inhibitor,
suggesting that dipotassium glycyrrhizinate might enhance the activation of PKC
via sodium deoxycholate. The combined use of these two enhancers had no toxic
effects. These results provide useful, basic information on the action of these
absorption enhancers on drugs for which absorption is limited owing to polarity
or molecular size, or both.
PMID- 10197415
TI - The role of an alpha-amino group on H+ -dependent transepithelial transport of
cephalosporins in Caco-2 cells.
AB - The role of an alpha-amino group on interaction with the intestinal and renal
peptide carriers (PEPT 1 and PEPT 2, respectively) has been the subject of much
investigation. Studies have differed in their conclusions about the role of an
alpha-amino group on carrier-mediated absorption. Most studies have used brush
border membrane vesicles or perfused intestinal segments. These techniques enable
the determination of membrane uptake and luminal disappearance, respectively, but
not transepithelial transport. Transepithelial transport should be more
predictive of absorption because it includes basolateral efflux, which could be
the rate-limiting process in drug absorption. The objective of this study was to
evaluate the influence of an alpha-amino group on PEPT 1-mediated transepithelial
transport in Caco-2 cells. The apical-to-basolateral permeability coefficients of
cephalosporins with or without a free alpha-amino group were determined in the
presence and absence of a pH gradient. Permeability coefficients obtained under
these conditions were used to calculate a permeability ratio (i.e. P(app) (pH
6.0)/P(app) (pH 7.4)), which should indicate whether PEPT 1 is involved in
transport. For cephalosporins with an alpha-amino group (cephalexin, cefaclor,
cefadroxil, cephradine, cephaloglycin) the permeability ratios ranged between
1.77 and 2.77. In contrast, the permeability ratios for cephalosporins without an
alpha-amino group were 1 (approx.; range = 0.74-1.26). These data suggest that
the presence of an alpha-amino group on cephalosporins increases their PEPT 1
mediated transepithelial transport in Caco-2 monolayers.
PMID- 10197416
TI - Determination of the affinity of drugs toward serum albumin by measurement of the
quenching of the intrinsic tryptophan fluorescence of the protein.
AB - Binding of new chemical entities to serum proteins is an issue confronting
pharmaceutical companies during development of potential therapeutic agents. Most
drugs bind to the most abundant plasma protein, human serum albumin (HSA), at two
major binding sites. Excepting fluorescence spectroscopy, existing methods for
assaying drug binding to serum albumin are insensitive to higher-affinity
compounds and can be labour-intensive, time-consuming, and usually require
compound-specific assays. This led us to examine alternative ways to measure drug
albumin interaction. One method described here uses fluorescence quenching of the
single tryptophan (Trp) residue in HSA excited at 295 nm to measure drug-binding
affinity. Unfortunately, many compounds absorb, fluoresce, or both, in this UV
wavelength region of the spectrum. Several types of binding phenomenon and
spectral interference were identified by use of six structurally unrelated
compounds and the equations necessary to make corrections mathematically were
derived and applied to calculate binding constants accurately. The general cases
were: direct quenching of Trp fluorescence by optically transparent ligands with
low or high affinities; binding of optically transparent, non-fluorescent ligands
to two specific sites where both sites or only one site result in Trp
fluorescence quenching; and chromophores whose absorption either overlaps the Trp
emission and quenches by energy transfer or absorbs light at the Trp fluorescence
excitation wavelength producing absorptive screening as well as fluorescence
quenching. Unless identification of the site specificity of drug binding to serum
albumin is desired, quenching of the Trp fluorescence of albumin by titration
with ligand is a rapid and facile method for determining the binding affinities
of drugs for serum albumin.
PMID- 10197417
TI - Protein binding of piroxicam studied by means of affinity chromatography and
circular dichroism.
AB - The protein binding of piroxicam, a widely used non-steroidal anti-inflammatory
drug has been investigated by high-performance liquid affinity chromatography,
with phenylbutazone and diazepam used as markers for binding-site
characterization, and by circular dichroism titration. It was found that
piroxicam binds to high-affinity phenylbutazone-binding sites and to high
affinity diazepam-binding sites. No binding to the low-affinity sites of either
marker was established. High values of the primary (high-affinity) binding
constants corresponding to both types of binding site were obtained by means of a
mathematical method cited in the literature. The circular dichroic spectra of
piroxicam were studied at a given albumin concentration and various drug
concentrations. A new Cotton effect was observed and was ascribed to the binding
of piroxicam to the protein molecule. The values of differential molar
ellipticity (delta theta) were treated by a new mathematical procedure for
analysis of the data obtained. A high affinity constant was calculated for one
class of binding site. Its value is in good agreement with the values obtained by
affinity chromatography. These results reveal that circular dichroism is an
acceptable method for investigation of protein binding.
PMID- 10197418
TI - Identification of urinary metabolites of clemastine after oral administration to
man.
AB - The metabolism of clemastine, 2-[2-[1-(4-chlorophenyl)-1-phenylethoxylethyl])-1
methylpyrrolidin e, has been studied in three adult male volunteers after a
single oral dose of 20 mg as the fumarate. After enzymatic hydrolysis solvent
extracts of urine were derivatized with N-methyl-N
trimethylsilyltrifluoroacetamide-ammonium iodide and analysed by gas
chromatography-mass spectrometry. The structures of metabolites were determined
on the basis of electron impact and chemical ionization mass spectra and the
identities of some (e.g. carbinol, 4-chlorobenzophenone and 4
chlorophenylstyrene) were confirmed by use of authentic standards. The principal
route of metabolism of clemastine in man involves direct oxidation, O
dealkylation (fission of the ether bond), aromatic hydroxylation, aliphatic
oxidation, alcoholic dehydration, and then enzymatic hydrolysis. Of the total
amount of metabolites excreted in the urine 35% was carbinol (metabolite M3,
major metabolite), 15% was M1, 17% was M2, 11% was M4, 9% was M5, 8% was M6 and
5% was M7.
PMID- 10197419
TI - Efficient biliary excretion of susalimod, probably via the bromosulphthalein
carrier, studied in a chronic bile fistula model in dogs.
AB - Susalimod is a structural analogue of sulphasalazine, known to be extensively
excreted in the bile in various animal species and for inducing bile duct
hyperplasia after long-term treatment of the dog with doses exceeding 25 mg kg(
1). In this study local concentrations of susalimod in the bile duct were
determined after oral administration in dogs. A chronic bile fistula experimental
model was designed to affect the bile duct as little as possible. The dogs
received repeated oral doses of 25-150 mg kg(-1) day(-1) for 5 days; these doses
had been used in previous toxicology studies. Extremely high biliary
concentrations of unchanged susalimod (20,000-43,000 microM) were measured.
Biliary excretion approached saturation at the higher doses, resulting in super
proportional increases in peripheral plasma concentrations as the dose was
increased. The maximal bile/plasma concentration ratio was 4300. The high biliary
clearance was indicative of almost complete first-pass elimination at doses below
saturation of the elimination process. Interaction studies with the biliary
excretion marker bromosulphthalein (BSP) demonstrated that susalimod and BSP
probably share the same carrier transport system in biliary excretion. The
elimination of BSP from plasma was prolonged 20 times and the biliary excretion
rate was markedly reduced when susalimod was co-administered with BSP. These
results show that susalimod is highly enriched in the bile, in a saturable
manner, after oral administration. The compound interacts with the biliary
excretion of BSP, suggesting that it shares the same carrier-mediated transport
system.
PMID- 10197420
TI - Dose-dependent intestinal and hepatic first-pass metabolism of midazolam, a
cytochrome P450 3A substrate with differently modulated enzyme activity in rats.
AB - The dose-dependent first-pass metabolism of midazolam, a cytochrome P450 (CYP) 3A
substrate, was separately estimated in the intestine and liver after
administration into a jejunal loop of rats with differently modulated enzyme
activity. Modulation of CYP3A enzyme activity of Sprague-Dawley rats was
performed by pretreating the rats with inducers such as dexamethasone or by co
administering ketoconazole (an inhibitor) with midazolam. Bioavailabilities of
midazolam administered into the jejunal loop at a dose of 10 micromol were 12% in
untreated (control) rats, and 2% in dexamethasone-pretreated rats. Co
administered ketoconazole (2 micromol) significantly increased the
bioavailability to 53% and 7%, respectively, in these rats. The intestinal first
pass metabolism of midazolam administered into the jejunal loop at a dose of 50
nmol in untreated and dexamethasone-pretreated rats, estimated by the mesenteric
blood-collecting method in-situ, was 25% and 49% of absorbed amount,
respectively. The intestinal first-pass metabolism of midazolam was reduced when
ketoconazole (0.5 micromol) was co-administered or when the dose of midazolam was
increased to 0.5 micrommol in these rats. Assuming that the contribution of
intestinal first-pass metabolism could be negligible when midazolam was
administered at a much higher dose of 10 micromol, the estimated hepatic first
pass metabolism of midazolam at a dose of 10 micromol in untreated rats,
dexamethasone-pretreated rats, untreated rats given ketoconazole, and
dexamethasone-pretreated rats given ketoconazole was, respectively, 86, 97, 46,
and 92% of the amounts absorbed. In conclusion, the dose-dependent intestinal
first-pass metabolism and the hepatic first-pass metabolism of midazolam in rats
with differently modulated CYP3A activities was quantitatively estimated by in
vivo and in-situ absorption studies.
PMID- 10197421
TI - Debromination of (alpha-bromoiso-valeryl)urea catalysed by rat blood.
AB - (Alpha-bromoiso-valeryl) urea, a sedative or hypnotic, is metabolized to (3
methylbutyryl)urea by reductive debromination. This study was designed to
evaluate the role of blood in the debromination of (alpha-bromoiso-valeryl) urea.
Rat blood containing an electron donor had significant debrominating activity
toward (alpha-bromoiso-valeryl)urea. This debromination proceeded by enzymatic
and non-enzymatic processes which required both NADH (or NADPH) and flavin
mononucleotide (FMN), under anaerobic conditions. The debrominating activity was
sensitive to inhibition by carbon monoxide, and the pH optimum was 8.5. When FMN
was replaced by flavin adenine dinucleotide (FAD) or riboflavin, similar results
were obtained. The optimum concentration of flavins was 10(-4) M. The reductive
debromination was also mediated by rat erythrocytes, but not by plasma. When the
blood or erythrocytes were boiled, the debrominating activity was not abolished,
but was enhanced, suggesting that the activity arises from the haemoglobin in
erythrocytes, and haemoglobin had debrominating activity when supplemented with
both a reduced pyridine nucleotide and a flavin. Furthermore, haematin had
significant debrominating activity in the presence of these cofactors. The
activity of haematin was also observed with the photochemically reduced form of
FMN. The results imply that the debromination proceeds in two steps--enzymatic or
non-enzymatic reduction of a flavin such as FAD, FMN or riboflavin by NADPH or
NADH, then non-enzymatic reductive debromination of (alpha-bromoiso-valeryl)urea
to (3-methylbutyryl)urea catalysed by the haem group of rat haemoglobin in the
presence of the reduced flavin.
PMID- 10197422
TI - Reductive debromination of (alpha-bromoiso-valeryl)urea by intestinal bacteria.
AB - The reductive debromination of the hypnotic (alpha-bromoiso-valeryl)urea to (3
methylbutyryl)urea by intestinal bacteria has been studied. The caecal contents
of rats, mice, hamsters, guinea-pigs and rabbits had significant debrominating
activity toward (alpha-bromoiso-valeryl)urea. The cell-free extract of intestinal
bacteria from the caecal contents of rats had debrominating activity in the
presence of both flavin mononucleotide (FMN) and NADH (or NADPH) under anaerobic
conditions. Seven pure strains of intestinal bacteria were also tested and the
highest activity was observed with Clostridium sporogenes. The cell-free extract
of Clostridium sporogenes had debrominating activity in the presence of both FMN
and NADH (or NADPH), and this activity was inhibited by sodium arsenite and
potassium cyanide. The activity of the cell-free extract was also supported by
the photochemically reduced form of FMN. The debromination in intestinal bacteria
seems to proceed in two steps--reduction of flavins by bacterial flavin
reductase(s) in the presence of NADPH or NADH, and then the reductive
debromination of (alpha-bromoiso-valeryl)urea to (3-methylbutyryl)urea by
bacterial dehalogenase(s) using the reduced flavins as an electron donor. These
results indicate that intestinal bacteria play a role in the reductive
debromination of (alpha-bromoiso-valeryl)urea to (3-methylbutyryl)urea in
animals. The debromination is inhibited by oxygen and dependent on flavins.
PMID- 10197423
TI - Interspecies pharmacokinetic comparisons and allometric scaling of napsagatran, a
low molecular weight thrombin inhibitor.
AB - The objective of this work was to assess the pharmacokinetics of napsagatran, a
low molecular weight thrombin inhibitor, after intravenous administration in a
variety of laboratory animals, and prospectively to help design the first
pharmacokinetic studies in man. Napsagatran is actively excreted into the bile
and urine of various species and pronounced species-differences in its
pharmacokinetics are observed. It is, therefore, an interesting compound to use
in tests of the limitations of presently available inter-species scaling methods.
The present data suggest that allometric exponent values which are consistent
with the values expected for physiological processes and small organic molecules
are not necessarily associated with successful predictions in man when active
transport processes are involved in the disposition of the compounds. For
example, compared with the values observed in man, the clearance (CL), non-renal
clearance (CL(nr)) and the volume of distribution at steady state (Vd(ss)) were
over-predicted by 3-, 7- and 2-fold, respectively, by use of allometry. Of the
species tested, the cynomolgus monkey seemed to be the most useful for predicting
kinetics in man when the approach based on concentration-time transformations was
used. Thus, for half-life (t(1/2)), CL and Vd(ss), the observed mean values of
1.7 h, 459 mL min(-1) and 24 L kg(-1) in man were very close to the values
predicted from the cynomolgus monkey (1.7 h, 652 mL min(-1) and 22 L kg(-1),
respectively). The results show that there are large inter-species differences
for kidney and liver excretion of napsagatran. This is probably because of the
involvement of active transport processes, which compromised the kinetic
extrapolation from animal to man, although a more thorough investigation of the
transporters involved in the disposition of napsagatran is necessary to enable
better understanding of the species differences observed.
PMID- 10197424
TI - Synergistic effects of anthraquinones on the purgative activity of rhein anthrone
in mice.
AB - This study was performed to determine whether intracaecally administered rhein
anthrone and anthraquinones such as aloe-emodin, chrysophanol, emodin or rhein
synergistically enhance the purgative action as has been observed for rhein
anthrone and aloe-emodin anthrone. These anthraquinones were less potent than
rhein anthrone. An equimolar mixture of aloe-emodin and rhein anthrone had
synergistic potentiating effects because the ED50 value (50% purgative dose) of
the combination was smaller than that calculated additively from the ED50 values
of aloe-emodin and rhein anthrone. An equimolar mixture of other anthraquinones
and rhein anthrone tended to potentiate the purgative action. These results
confirmed that rhein anthrone and aloe-emodin synergistically exert a purgative
action as has been observed for rhein anthrone and aloe-emodin anthrone.
PMID- 10197426
TI - Preventive effects of a mixed disulphide from dithiocarbamate and N
acetylcysteine on the genotoxicity of N-nitrosodiethylamine.
AB - A mixed disulphide model compound, S-(N,N-diethyldithiocarbamoyl)-N
acetylcysteine (AC-DDTC), prepared from diethyldithiocarbamate and N
acetylcysteine, was investigated for protective effects against the genotoxicity
of the environmental carcinogen N-nitrosodiethylamine (NDEA). AC-DDTC was found
to be a potent inhibitor of genotoxicity induced by NDEA. The mutagenicity of
NDEA to Salmonella typhimurium was inhibited by 70% at 3.2 micromol AC-DDTC per
plate and the effect was dose-dependent. In the chromosome aberration assay, NDEA
elicited a significant increase in the number of aberrant cells. Pretreatment
with AC-DDTC suppressed the chromosome-damaging effect of NDEA. The micronucleus
inducing capacity of NDEA was reduced by 32% by treatment with AC-DDTC at 1.5
mmol kg(-1). These results suggest that AC-DDTC might have a role to play in
reducing the risk of cancer induced by NDEA.
PMID- 10197425
TI - Honokiol, a putative anxiolytic agent extracted from magnolia bark, has no
diazepam-like side-effects in mice.
AB - Use of the elevated plus-maze experiment and activity and traction tests in mice
have revealed that seven daily treatments with 0.2 mg kg(-1) and higher doses of
honokiol, a neolignane derivative extracted from Magnolia bark, had an anxiolytic
effect without change in motor activity or muscle tone. Diazepam, 1 mg kg(-1),
had the same anxiolytic potential as 0.2 mg kg(-1) honokiol but induced muscle
relaxation. The aim of this study was to determine whether honokiol had diazepam
like side-effects. Mice treated with 1-10 mg kg(-1) diazepam, but not those
treated with 0.1-2 mg kg(-1) honokiol, for 12 days showed withdrawal symptoms
characterized by hyperactivity and running-fit when they were challenge
administered intraperitoneal flumazenil (10 mg kg(-1)) 24 h after the last
treatment with diazepam. Oral diazepam (0.5-2 mg kg(-1), 10 min before) dose
dependently prolonged hexobarbital (100 mg kg(-1), i.p.)-induced sleeping,
disrupted learning and memory, and inhibited (+)-bicuculline (40 mg kg(-1), i.p.)
induced death. Honokiol (0.2-20 mg kg(-1), p.o., 3 h before) had no such effects.
The prolongation by diazepam (1 mg kg(-1)) of hexobarbital-induced sleeping was
not modified by honokiol (0.2-20 mg kg(-1)). These results suggest that honokiol
is less likely than diazepam to induce physical dependence, central depression
and amnesia at doses eliciting the anxiolytic effect. It is also considered that
honokiol might have no therapeutic effect in the treatment of convulsion.
PMID- 10197427
TI - Expression profiling in cancer using cDNA microarrays.
AB - Currently there are over 1,000,000 human expressed sequence tag (EST) sequences
available on the public database, representing perhaps 50-90% of all human genes.
The cDNA microarray technique is a recently developed tool that exploits this
wealth of information for the analysis of gene expression. In this method, DNA
probes representing cDNA clones are arrayed onto a glass slide and interrogated
with fluorescently labeled cDNA targets. The power of the technology is the
ability to perform a genome-wide expression profile of thousands of genes in one
experiment. In our review we describe the principles of the microarray technology
as applied to cancer research, summarize the literature on its use so far, and
speculate on the future application of this powerful technique.
PMID- 10197428
TI - Differential display competitive polymerase chain reaction: an optimal tool for
assaying gene expression.
AB - Gene discovery, i.e. detection of genes whose expression is affected in diseases
or by different treatments of cells or animals, has become the focus of much
genetic research. The technologies that are used to detect changes in expression
level include polymerase chain reaction (PCR)-based subtraction methods, arrays
of cDNA clones on chips or filters, serial analysis of gene expression, and
differential display. In this paper we show that differential display can be used
to investigate global gene expression in situations where a few genes change
expression levels such as exposure of MCF7 cells to estradiol, and in more
complex situations such as neuronal differentiation of human NTERA2 cells which
affects a large number of genes. Furthermore, we show that differential display
can replace Northern blotting and RNase protection as a tool to study the
expression level of a specific gene in many samples. Results obtained by
differential display can be stored in databases, where the identity of a band
(gene or mRNA name) can be linked with information about the primer combination
displaying the band and a gel image showing the band pattern, which is all the
information that is needed to compare the expression level of this gene in other
samples.
PMID- 10197429
TI - Identification of true differentially expressed mRNAs in a pair of human bladder
transitional cell carcinomas using an improved differential display procedure.
AB - Differential display in combination with arbitrarily primed polymerase chain
reaction (PCR) fingerprinting has become one of the most powerful techniques to
identify and isolate mRNAs that are differentially expressed in pairs of
biological samples. However, in many cases the cDNA band corresponding to the
differentially amplified product contains several cDNA species that comigrate
with the cDNA of interest due to the poor resolution of the fingerprinting gels,
thus hampering further analysis and identification of the desirable cDNA. To
improve the electrophoretic resolution of differentially amplified cDNAs, we have
utilized Resolver Gold agarose gel electrophoresis (Ingenius) as an additional
step to overcome downstream problems encountered during RNA fingerprinting
experiments. To illustrate the power of the modified differential display
procedure we present a detailed analysis of the cDNA products differentially
displayed in tumor biopsies obtained from a noninvasive (grade II, Ta) and an
invasive (grade III, T2-T4) human bladder transitional cell carcinoma (TCC).
Several genes that were differentially expressed in this tumor pair were
identified. These included: tropomyosin 4, the protein disulfide isomerase
precursor (PDI), MRP14, signal transducer CD24, keratins 8 and 13, cytochrome
oxidase subunit IV (COXIV), putative transcription factor HOX-1.3, as well as two
novel genes of yet unknown function. All of the identified cDNAs were shown to be
truly differentially expressed by Northern blotting, reverse transcriptase-PCR
(RT-PCR), and two-dimensional polyacrylamide gel electrophoresis (2-D PAGE)
analysis of the corresponding lesions.
PMID- 10197430
TI - muFKBP38: a novel murine immunophilin homolog differentially expressed in
Schwannoma cells and central nervous system neurons in vivo.
AB - To better understand the process of multistage carcinogenesis in Schwann cells,
we have attempted to isolate novel candidate genes involved in neoplastic
progression of mouse malignant Schwannoma cells. The semi-differentiated
Schwannoma cell line 56-24 and the less differentiated Schwannoma cell line 64-39
were established from peripheral nerve sheath tumors arising in transgenic mice
of the MBP/SV40 large T strain Tg29. By using the chemical cross-linking
subtraction technique, we have cloned a novel murine cDNA that detects pronounced
expression in 56-24 cells but not in 64-39 cells. The longest open reading frame
of the cDNA predicts a peptide showing 95% amino acid sequence homology to the
recorded sequence of the human immunophilin homolog huFKBPr38, one of a family of
proteins that are thought to interface with a wide range of intracellular signal
transduction systems. The predicted open reading frame of the corresponding gene,
named muFKBP38, encodes a 38 kDa protein that harbors an FK-binding protein
(FKBP) domain that is 36% identical to that of muFKBP52, a three-unit
tetratricopeptide repeat and a consensus leucine-zipper repeat. Although muFKBP38
mRNA was detected in both neurons and glial cells, pronounced expression of the
immunophilin homolog appeared in various classes of neurons associated with the
hippocampal formation, as shown by in situ hybridization analysis of adult mouse
brains. Taken together, these data indicate that muFKBP38 is (i) a novel
potential marker for semi-differentiated Schwannomas, (ii) may form homomultimers
and/or interact with other proteins, and (iii) may have a role in neurons
associated with memory function.
PMID- 10197431
TI - Differential display, subtractive hybridization, and application of methodology
to search for point mutations to identify genetic defects responsible for
progression in MCF10AT model of human breast disease.
AB - We describe initial studies utilizing three methods to detect differences in gene
expression: (i) differential display with polyT-anchored primers; (ii)
differential display with RNA arbitrarily primed polymerase chain reaction (RAP
PCR), and (iii) cDNA subtractive hybridization. Subtractive hybridization, which
detects qualitative differences in gene expression, revealed no differences
between a human cell line (MCF10A), originated by spontaneous immortalization of
breast epithelial cells, and MCF10CA1 cells, a recently derived fully malignant,
metastatic variant. The standard method of differential display with polyT
anchored primers detected in excess of 100 differentially displayed bands but
differential expression could seldom be verified by Northern blotting. However,
RAP-PCR products frequently represent the coding region and fewer bands are
detected. One gene of interest is a zinc finger protein which may be expressed
more in the preneoplastic lesion-forming cells than in nonlesion-forming cells.
Because most bands are not consistently differentially displayed among the
variants of the MCF10 model, we suspect that point mutations rather than
differential quantitative gene expression is responsible for some stage of
progression. We propose that differential display of RAP-PCR products on
nondenaturing gels might also detect point mutation differences.
PMID- 10197432
TI - Functional genomics in cancer research: identification of target genes of the
Epstein-Barr virus nuclear antigen 2 by subtractive cDNA cloning and high
throughput differential screening using high-density agarose gels.
AB - In the past, the identification and isolation of phenotype-associated genes was a
difficult and time-consuming task. However, recent improvements of methods that
are designed to isolate differentially expressed genes have remarkably speeded up
the process of target gene isolation. The ultimate goal of functional genomics is
to apply these technologies to clone phenotype-associated genes irrespective of
the availability of probes (e.g., antibodies) and an intimate knowledge of
biological background. We demonstrate the use of a novel subtractive cDNA cloning
approach for the isolation and characterization of target genes of the Epstein
Barr virus nuclear antigen 2 (EBNA2). Two different subtractive cDNA libraries
specific for two different time periods following activation of a conditional
estrogen receptor/EBNA2 (ER/EBNA2) fusion protein were generated. Comparison of
the two libraries by cross-hybridization experiments allowed the differentiation
between direct and indirect target genes of EBNA2 and led to the identification
of a novel direct target gene of EBNA2.
PMID- 10197433
TI - Identification of novel bladder tumour suppressor genes.
AB - Many genetic alterations have recently been identified in transitional cell
carcinoma (TCC) of the bladder. These include alterations to known proto
oncogenes and tumour suppressor genes and the identification of multiple sites of
nonrandom chromosomal deletion which are predicted to define the location of as
yet unidentified tumour suppressor genes. This review summarises recent efforts
to define the location of novel bladder tumour suppressor genes using loss of
heterozygositiy (LOH) and homozygous deletion analyses and to isolate the genes
targeted by these deletions. For three of the four regions of deletion on
chromosome 9, the most frequently deleted chromosome in TCC, candidate genes have
been identified. It is anticipated that the identification of the genes and/or
genetic regions which are frequently altered in TCC will provide useful tools for
diagnosis, prediction of prognosis, patient monitoring and novel therapies.
PMID- 10197434
TI - Molecular genetic diagnosis of de novo and recurrent bladder cancer.
AB - Bladder cancer, the second most common urological tumor, is usually diagnosed by
endoscopy and biopsy of the lower urinary tract. However, this procedure is
expensive, can cause discomfort to the patient and is a source of infection.
Commercially available diagnostic systems measure protein byproducts of bladder
carcinoma in voided urine; their sensitivity is only between 60-80%. Polymerase
chain reaction (PCR)-based microsatellite analysis of the urine sediment (MAUS)
is a noninvasive, inexpensive and easily performed analytical method which was
introduced in the de novo diagnosis and follow-up of bladder cancer. By utilizing
the PCR with 20 polymorphic microsatellite markers on different chromosomes and
separating PCR products by electrophoresis on 7% denaturing polyacrylamide
formamide-urea slab gels, a 91% diagnostic sensitivity could be achieved. In
order to minimize costs and analysis time, the separation and detection of PCR
products was carried out by capillary array electrophoresis and two-color
fluorescent primer labeling/laser beam detection in another study. The accuracy
of both methods was the same. In either detection system, MAUS is an accurate and
promising tool in the noninvasive diagnosis of bladder cancer.
PMID- 10197435
TI - The use of arbitrarily primed polymerase chain reaction in cancer research.
AB - There is a great need for techniques that detect the genome alterations present
in cancer cells. Here, we present a review of the arbitrarily primed polymerase
chain reaction (AP-PCR), a genomic mutation detection method with some unique
advantages: (i) It can detect most types of mutations that usually occur in
tumors (except point mutations). (ii) It is especially useful to detect moderate
gains in DNA, which most methods currently in use cannot detect. (iii) It allows
detection and cloning of alterations in a single experiment. (iv) It is
inexpensive and does not require special equipment. We discuss some
characteristics of this method and review some of its achievements in cancer
research.
PMID- 10197436
TI - Proviral load determination of different feline immunodeficiency virus isolates
using real-time polymerase chain reaction: influence of mismatches on
quantification.
AB - Lentiviruses are associated not only with immunodeficiency but also with
malignancies. The mechanisms involved in tumorigenesis are still not fully
understood. Cats infected with feline immunodeficiency virus (FIV) in the wild
represent one model in which the role of viral load in the pathogenesis can be
studied, since tumors, especially lymphomas, are quite often observed in cats
infected with FIV. To be able to compare the viral load data among cats infected
with different FIV isolates, the method used to obtain the viral load has to be
unaffected by isolate-specific differences. This is especially true for the real
time polymerase chain reaction (PCR), a new method for viral load determination,
since nucleotide sequence mismatches have been used for allelic discrimination
with this method. To investigate the influence of these mismatches on PCR
efficiency, we have used an FIV-specific real-time PCR and determined the
influence of nucleotide sequence variation in several characterized FIV isolates
as well as unknown isolates from naturally infected cats. We could demonstrate
that minor mismatches, such as point mutations in the primer or the probe region,
decrease overall PCR efficiency but do not abolish the quantification, in
contrast to major mismatches of three or four nucleotides, which lead to complete
inhibition of the real-time PCR detection. Based on these results, it will be
possible to design real-time PCR systems allowing the quantification of a broad
range of isolates, which is a prerequisite for the investigation of the impact of
viral load in tumorigenesis.
PMID- 10197437
TI - A comprehensive protein resource for the study of bladder cancer:
http://biobase.dk/cgi-bin/celis.
AB - In our laboratories we are exploring the possibility of using proteome expression
profiles of fresh bladder tumors (transitional cell carcinomas, TCCs; squamous
cell carcinomas, SCCs) and random biopsies as fingerprints to subclassify
histopathological types and as a starting point to search for protein markers
that may form the basis for diagnosis, prognosis, and treatment. Ultimately, the
goal of these studies is to identify signaling pathways and components that are
affected at various stages of bladder cancer progression and that may provide
novel leads in drug discovery. Here we present our ongoing efforts to establish
comprehensive two-dimensional polyacrylamide gel electrophoresis (2-D PAGE)
databases of TCCs and SCCs which are being constructed based on the proteomic and
immunohistochemical analysis of hundreds of fresh tumors, random biopsies and
cystectomies received shortly after operation (http://biobase.dk/cgi-bin/celis).
PMID- 10197438
TI - Protein analysis by mass spectrometry and sequence database searching: tools for
cancer research in the post-genomic era.
AB - The post-genomic era is characterized by the deposition of sequence information
for entire genomes in databases. Currently, besides the protein sequences for
known human proteins, there are partial sequences from thousands more human
proteins for which no biological function has been assigned. A powerful new tool
for the unambiguous identification and characterization of gel-separated proteins
is accomplished by the combination of mass spectrometry and sequence database
searching. This combination provides the cancer biologist with the ability to (i)
identify the potential protein:protein associations and (ii) fully characterize
function-critical post-translational modifications, both directly from silver
stained polyacrylamide gels. In this report we describe the application of tandem
mass spectrometry and database searching to two problems which are prototypical
for cancer research and indeed for biomedical research in general. The first is
the identification of gel-separated, low abundance proteins based on amino acid
sequence composition following coimmunoprecipitation with the human apoptosis
inhibitor protein BclX(L). The second is the determination of the precise sites
of phosphorylation of the human regulatory protein 4E-BP1, which controls mRNA
translation.
PMID- 10197439
TI - Study of Burkitt lymphoma cell line proteins by high resolution two-dimensional
gel electrophoresis and nanoelectrospray mass spectrometry.
AB - We paper describe a mass spectrometric approach generally applicable for the
rapid identification and characterization of proteins isolated by two-dimensional
gel electrophoresis (2-DE). The highly sensitive nanoflow-electrospray mass
spectrometry employing a quadrupole-time of flight mass spectrometer was used for
the direct identification of proteins from the peptide mixture generated from
only one high resolution 2-DE gel without high performance liquid chromatography
(HPLC) separation or Edman sequencing. Due to the high sensitivity and high mass
accuracy of the instrument employed, this technique proved to be a powerful tool
for the identification of proteins from femtomole amounts of materials. We
applied the technique for the investigation of Burkitt lymphoma BL60 cell
proteins. This cell line has been used as a model to assign apoptosis-associated
proteins by subtractive analysis of normal and apoptotic cells. From the nuclear
fraction of these cells, 36 protein spots were examined, from only one
micropreparative Coomassie Brilliant Blue R-250 stained gel, after proteolytic
digestion by matrix assisted laser desorption ionization (MALDI) and nanospray
mass spectrometry (MS). In combination with database searches, of 33 proteins
were successfully identified by nanospray-MS/MS-sequencing of up to eight
peptides per protein. Three proteins were new proteins not listed in any of the
available databases. Some of the identified proteins are known to be involved in
apoptosis processes, the others were common proteins in the eukaryotic cell. The
given technique and the protein data are the basis for construction of a database
to compare normal and apoptosis-induced cells and, further, to enable fast
screening of drug impact in apoptosis-associated processes.
PMID- 10197440
TI - Loss of epithelial polarity is accompanied by differential association of
proteins with intracellular membranes.
AB - Cellular membranes play an important role in the formation and maintenance of
epithelial polarity, which is lost early during carcinogenesis. We set out to
identify membrane proteins which are altered during loss of cell polarity in
mammary epithelium. As a model system we used murine mammary epithelial cells
expressing the conditional oncoprotein c-JunER, which induces a reversible loss
of polarity upon beta-estradiol-driven activation [1]. When grown either in the
absence or presence of hormone, these cells exhibit a polarized or unpolarized
phenotype, respectively. Different membrane fractions of polarized or unpolarized
cells were analyzed by two-dimensional electrophoresis (2-DE) and differentially
expressed membrane proteins were identified. To distinguish between transmembrane
orientation and peripheral attachment of these proteins, were performed
extractions with carbonate at high pH or with Triton X-114. In addition,
cytosolic proteins of both states were analyzed to investigate their differential
association with distinct membrane fractions. We found ten protein spots
preferentially or exclusively in polarized cells and 17 other proteins as being
upregulated during loss of polarity. Some of the peripheral membrane proteins
were identified by microsequencing. The resident Golgi protein nucleobindin and
fructose-bisphosphate aldolase were preferentially associated with membranes of
polarized cells, whereas alphaB crystallin was detected exclusively and in high
amounts in unpolarized cells.
PMID- 10197441
TI - Interferon gamma regulates a unique set of proteins in fresh human bladder
transitional cell carcinomas.
AB - Poly(A) mRNA was isolated from human placental trophoblast cells stimulated with
100 U/mL of interleukin-2 and 5 microg/mL of phytohemagglutinin and reverse
transcribed. The cDNA coding for the mature interferon-gamma (IFN-gamma) protein
was amplified using specific primers, cloned into the pGEX-4T2 vector, and
expressed in Escherichia coli. Treatment of four fresh bladder transitional cell
carcinoma (TCC) biopsies (TCCs 845-1, grade II, Ta; TCC 925-1, grade II, Ta; TCC
919-1, grade III, T1; TCC 950-1, grade III, T1) with the purified recombinant
trophoblast IFN-gamma (50 U/mL, 20 h), followed by proteome analysis using two
dimensional gel electrophoresis, revealed several major proteins whose level of
expression were affected by this cytokine. Of these, five (tryptophanyl-tRNA
synthetase, the interferon gamma-inducible protein gamma3, mangase superoxide
dismutase, and two unknown proteins of apparent molecular masses of 35.8 and 11.2
kDa, respectively) were upregulated in at least 75% of the tumors analyzed while
one was downregulated (aldose reductase). Proteins were identified using a
combination of techniques that included microsequencing, two-dimensional
polyacrylamide gel electrophoresis (2-D PAGE) immunoblotting and comparison with
the transitional cell carcinoma isoelectric focusing (IEF) database
(http://biobase.dk/cgi-bin/celis). Proteome profile analysis of primary cultures
from a low-grade lesion (TCC 846-1, Grade II, Ta) labeled in the presence and
absence of IFN-gamma showed that all of the proteins disregulated in vivo were
also affected in the cultures. The cultured cells, on the other hand, exhibited
additional changes that were not detected in vivo and that may reflect adaptation
to the culturing conditions. Taken together, the results provide a first glance
at the effect of IFN-gamma on the protein expression profiles of TCCs, and in due
course may form the basis for more comprehensive studies aimed at evaluating the
usefulness of this cytokine in bladder cancer management.
PMID- 10197442
TI - Psoriasin (S100A7): a putative urinary marker for the follow-up of patients with
bladder squamous cell carcinomas.
AB - To search for bladder squamous cell carcinoma markers that are released to the
urine a blind and systematic analysis of the protein profiles of fresh tumors,
their secreted proteins, as well as the patient's urine was carried out using
state-of-the-art proteomic technology. We review the data concerning the putative
marker psoriasin (S100A7), which, alone or in combination with other biomarkers,
may be valuable for the noninvasive follow-up of patients bearing these tumors.
PMID- 10197443
TI - Short-term culturing of low-grade superficial bladder transitional cell
carcinomas leads to changes in the expression levels of several proteins involved
in key cellular activities.
AB - Fresh, superficial transitional cell carcinomas (TCCs) of low-grade atypia (3
grade I, Ta; 6 grade II, Ta), as well as primary cultures derived from them were
labeled with [35S]methionine for 16 h, between 2 and 6 days after inoculation.
Whole protein extracts were subjected to IEF (isoelectric focusing) two
dimensional polyacrylamide gel electrophoresis (2-D PAGE) followed by
autoradiography. Proteins were identified by a combination of proteomic
technologies that included microsequencing, mass spectrometry, 2-D PAGE
immunoblotting and comparison with the bladder TCC protein database available on
the internet (http://biobase.dk/cgi-bin/celis). Comparison of the IEF 2-D gel
protein profiles of fresh tumors and their primary cultures showed that the
overall expression profiles were strikingly similar, although differing
significantly in the levels of several proteins whose rate of synthesis was
differentially regulated in at least 85% of the tumor/culture pairs as a result
of the short-term culturing. Most of the proteins affected by culturing were
upregulated and among them we identified components of the cytoskeleton (keratin
18, gelsolin and tropomyosin 3), a molecular chaperone (hsp 28), aldose
reductase, GST pi, metastasin, synuclein, the calreticulin precursor and three
polypeptides of unknown identity. Only four major proteins were downregulated,
and these included two fatty acid-binding proteins (FABP:FABP5 and A-FABP) which
are thought to play a role in growth control, the differentiation-associated
keratin 20, and the calcium-binding protein annexin V. Proteins that were
differentially regulated in only some of the cultured tumors included alpha
enolase, triosphosphate isomerase, members of the 14-3-3 family, hnRNPs F and H,
PGDH, hsp (heat-shock protein) 60, BIP, the interleukin-1 receptor antagonist,
the nucleolar protein B23, as well as several proteins of yet unknown identity.
The suitability of in vitro bladder tumor culture models to study complex
biological phenomena such as malignancy and invasion is discussed.
PMID- 10197444
TI - Clinical aspects of altered glycosylation of glycoproteins in cancer.
AB - Alteration of the expression of carbohydrate structures is frequently observed in
tumor cells. This review summarizes the different changes of O- and N-linked
glycoproteins observed in cancer cells, the impact of the tumor-related
carbohydrate phenotypes on the clinical outcome of the cancer disease, and the
various ways in which carbohydrate structures can interact with different
carbohydrate-detecting adhesion molecules, selectins, and sialoadhesins. Various
ways of inhibiting the formation of cell adhesion-engaged carbohydrates on the
cell surface, or inhibiting the binding are discussed. Carbohydrate structures
which are in clinical use as circulating tumor markers and the effect of
genotypes on tumor marker concentrations are reviewed.
PMID- 10197445
TI - Dissecting functions of the retinoblastoma tumor suppressor and the related
pocket proteins by integrating genetic, cell biology, and electrophoretic
techniques.
AB - The members of the 'pocket protein' family, comprising the retinoblastoma tumor
suppressor (pRB) and its relatives, p107 and p130, negatively regulate cell
proliferation and modulate fundamental biological processes including embryonic
development, differentiation, homeostatic tissue renewal, and defense against
cancer. The large, multidomain pocket proteins act by binding a plethora of cell
fate-determining and growth-stimulatory proteins, the most prominent of which are
the E2F/DP transcription factors. These protein-protein interactions are in turn
regulated by carefully orchestrated phosphorylation events on multiple serine and
threonine residues of pRB, p107, and p130, events which are carried out, at least
in part, by the cyclin-dependent kinases that form the key elements of the cell
cycle machinery. Here we discuss the recently obtained new insights into the
diverse functions of the pRB family, and show examples of how integration of
genetic, cell biology, and a range of electrophoretic approaches help to advance
our understanding of the biological roles played by the pocket proteins in both
normal and cancer cells.
PMID- 10197447
TI - Protein kinase CK2 and its role in cellular proliferation, development and
pathology.
AB - Protein kinase CK2 is a pleiotropic, ubiquitous and constitutively active protein
kinase that can use both ATP and GTP as phosphoryl donors with specificity for
serine/threonine residues in the vicinity of acidic amino acids. Recent results
show that the enzyme is involved in transcription, signaling, proliferation and
in various steps of development. The tetrameric holoenzyme (alpha2beta2) consists
of two catalytic alpha-subunits and two regulatory beta-subunits. The structure
of the catalytic subunit with the fixed positioning of the activation segment in
the active conformation through its own aminoterminal region suggests a
regulation at the transcriptional level making a regulation by second messengers
unlikely. The high conservation of the catalytic subunit from yeast to man and
its role in the tetrameric complex supports this notion. The regulatory beta
subunit has been far less conserved throughout evolution. Furthermore the
existence of different CK2beta-related proteins together with the observation of
deregulated CK2beta levels in tumor cells and the reported association of CK2beta
protein with key proteins in signal transduction, e.g. A-Raf, Mos, pg90rsk etc.
are suggestive for an additional physiological role of CK2beta protein beside
being the regulatory compound in the tetrameric holoenzyme.
PMID- 10197446
TI - Phosphorylation-dependent protein kinase D activation.
AB - The novel mouse serine-threonine kinase protein kinase D (PKD) is activated in
intact Swiss 3T3 cells stimulated by phorbol esters, cell permeant
diacylglycerols, bryostatin, neuropeptides and growth factors via a
phosphorylation-dependent mechanism requiring protein kinase C (PKC) activity.
Structural comparison of the PKD catalytic domain with other kinases reveals a
close similarity with MEK family kinases, which are activated upon
phosphorylation of key serine and threonine residues in a region termed the
activation loop. To study the regulation of PKD, we transfected mutant PKD cDNAs
in which putative activation loop serine residues 744 and 748 were mutated to
either alanine or glutamic acid into COS-7 cells. Replacement of serines 744 and
748 with alanine prevented activation of the overexpressed PKD form upon phorbol
ester treatment of cells, whereas replacement with glutamic acid results in full
constitutive activation. Single serine to glutamic acid replacement mutants were
partially activated. In vivo 32P-labeling and two-dimensional phosphopeptide
mapping of PKD and catalytically inactive PKD mutants at serine 744, 748 or at
both residues revealed that phorbol ester-sensitive phosphopeptides could be
selectively eliminated from patterns observed as a result of these mutations.
Treatment of cells with the PKC inhibitor GFI also prevented the appearance of
phosphopeptide spots occuring in response to phorbol ester stimulation. These
results provide direct evidence that PKD becomes activated in vivo as a
consequence of PKC-mediated phosphorylation of serines 744 and 748. These results
support our view of PKD as an important clement in PKC signal transduction.
PMID- 10197448
TI - Stathmin interaction with HSC70 family proteins.
AB - Stathmin is a ubiquitous cytosolic phosphoprotein participating in the relay and
integration of diverse intracellular signaling pathways involved in the control
of cell proliferation, differentiation, and activities. It is phosphorylated in
response to diverse extracellular signals including hormones and growth factors,
and it is highly expressed during development and in diverse tumoral cells and
tissues. Stathmin interacts with tubulin and other potential protein partners
such as BiP, KIS, CC1 and CC2/tsg101. In our present search for further
functional partners of stathmin, we identified proteins in the Hsp70 family, and
in particular Hsc70, as interacting with stathmin in vitro. Hsc70 is among the
proteins coimmunoprecipitated with stathmin, and it is the main protein retained
specifically on stathmin-Sepharose beads identified by one- and two-dimensional
electrophoresis and immunoblots. Bovine serum albumin (BSA)-Sepharose did not
bind Hsc70, and anti-stathmin antisera specifically inhibited the interaction of
Hsc70 with stathmin-Sepharose. The binding of Hsc70 to stathmin is dependent on
the phosphorylation status of stathmin, as it did not occur with a
"pseudophosphorylated" mutant form of stathmin. This interaction is further
dependent on the ATP status of Hsc70. It was inhibited in the presence of ATP
Mg++ but not in the presence of ATP-Mg++ and ethylenediaminetetraacetic acid
(EDTA) or of ADP. Our results suggest that the interaction of stathmin with Hsc70
is specific in both proteins and most likely biologically relevant in the context
of their functional implication in the control of numerous intracellular
signaling and regulatory pathways, and hence of normal cell growth and
differentiation.
PMID- 10197449
TI - The measurement of ubiquitin and ubiquitinated proteins.
AB - Ubiquitination of key cellular proteins involved in signal transduction, gene
transcription and cell-cycle regulation usually condemns those proteins to
proteasomal or lysosomal degradation. Additionally, cycles of reversible
ubiquitination regulate the function of certain proteins in a manner analogous to
phosphorylation. In this short review we describe the current methodology for
measuring ubiquitin and ubiquitination, provide examples which illustrate how
various techniques have been used to study protein ubiquination, alert the
readers of pitfalls to avoid, and offer guidelines to investigators newly
interested in this novel post-translational protein modification.
PMID- 10197450
TI - Magnetic resonance imaging in the evaluation of ligament injuries.
AB - Magnetic resonance imaging has had a dramatic effect on the means by which we
diagnose ligament injuries. Tears resulting from either acute trauma or overuse
can be detected noninvasively, directing appropriate therapy be it conservative
or surgical. For the elite athlete, earlier diagnosis leads to earlier
intervention, or alternatively, a normal MRI examination can result in an earlier
return to play. While MRI is accepted for the diagnosis of certain injuries such
as complete tears of the cruciate ligaments of the knee, other injuries, such as
partial cruciate ligament tears or tears of the intercarpal ligaments of the
wrist, remain controversial.
PMID- 10197451
TI - Intra-articular gouty tophi of the knee: CT and MR imaging in 12 patients.
AB - OBJECTIVE: To define the imaging characteristics of intra-articular tophi of the
knee. DESIGN AND PATIENTS: Twelve patients with intra-articular tophi in the knee
were studied with routine MR imaging, gadolinium (Gd)-enhanced MR imaging, and CT
over a 4-year period. There were 11 men and one woman, 25-82 years of age (mean
age 48 years). Four patients did not have a documented history of gout at the
time of the MR examination. The diagnosis of intra-articular tophi was provided
by arthroscopy and histological examination (5 patients), by microscopic study of
joint fluid (5 patients), or by characteristic clinical, laboratory and imaging
findings (2 patients). RESULTS: In 15 MR examinations the tophi were located
purely intra-articularly in 10 knees. In the remaining five MR studies,
periarticular soft tissues or bone, or both, were involved. All the intra
articular tophi manifested low to intermediate signal intensity on both T1- and
T2-weighted images. All five Gd-enhanced MR examinations demonstrated a
heterogeneous peripheral enhancement. All 10 CT scans showed varying degrees of
stippled calcifications within the tophi. The nature of the calcifications was
confirmed on histological examination in three patients. CONCLUSION: Presenting
clinical manifestations of gout may relate to intra-articular tophaceous
deposits. Such deposits present as masses on MR images with low to intermediate
signal intensity on both T1- and T2-weighted images and a characteristic
enhancement pattern following intravenous Gd administration. These features
relate primarily to internal calcifications, which are most evident on CT images.
MR evaluation (including Gd administration) supplemented, in some cases, with CT
scanning allows accurate diagnosis of intra-articular tophaceous deposits.
PMID- 10197452
TI - Unusual longitudinal stress fractures of the femoral diaphysis: report of five
cases.
AB - We present five cases of a distinctive type of longitudinal stress fracture of
the upper femoral shaft in which the fracture line is parallel to the outer
surface of the bone, in contrast to the perpendicular orientation to the cortical
surface in previously reported cases of diaphyseal stress fractures. In two cases
the fracture recurred after 15 and 18 months, respectively.
PMID- 10197454
TI - Density predicts the activity-dependent failure load of proximal femora with
defects.
AB - OBJECTIVE: To determine whether the load-bearing capacity of human proximal
femora with metastatic defects can be predicted from the bone mineral content.
DESIGN: The bone mineral content (BMC) of the total proximal femur was measured
by dual-energy X-ray absorptiometry (DXA). The femurs were loaded so as to
simulate stair ascent or external rotation. PATIENTS: Simulated lytic defects
were created using specialized cutting tools in the intertrochanteric region of
32 human cadaveric femora. Bone density measurements were made before and after
creating defects. RESULTS: A linear relation could be used to predict failure
load from BMC or bone mineral density. The slope of the linear relation was
greater for loads representing external rotation than for loads representing
stair ascent. The linear relations suggest that the BMC measurements account for
both the density of the host bone and the amount of bone removed by the defect.
CONCLUSIONS: The data suggest that between 70% and 80% of the variation in
failure load of human femora with lytic metastatic defects can be predicted from
the BMC and that relations between BMC and failure load are sensitive to the type
of loading. Combined with information on the loads associated with the activities
of daily living, these data may be used to help identify patients in whom
prophylactic stabilization might prevent a pathologic fracture.
PMID- 10197453
TI - Clinical significance of erosive azotemic osteodystrophy: a prospective masked
study.
AB - OBJECTIVE: To determine the relationship between joint symptoms and
radiographically identifiable erosions in patients on maintenance hemodialysis
for 4 or more years. PATIENTS AND DESIGN: A prospective study was carried out on
21 patients, who underwent rheumatological evaluation and radiographic surveys of
all clinically examined joints. The radiologist was masked to the clinical
information and the clinicians were masked to the radiographic findings.
Cuprophane dialyzers were used on all patients. The statistical analysis was
performed by unpaired t-test and Fisher's exact test. RESULTS AND CONCLUSIONS:
Ten men and 11 women comprised the 21 patients, of whom 10 had joint symptoms and
clinical signs whereas 11 did not. Age, gender, and duration of hemodialysis did
not differ significantly between the symptomatic and asymptomatic group. Of the
21 patients, 10 had radiological evidence of erosions and 11 did not. The average
age of patients with erosions was 64.9 years; this was significantly different
from the age of the group without erosions, which was 54.1 years. The group with
radiographic evidence of erosions had been on dialysis for an average of 9.6
years, while those without erosions had received dialysis for an average of 6.4
years. Of the 11 patients without radiographic evidence of erosions, three were
symptomatic. Of the 10 patients with erosions, seven had musculoskeletal
symptoms, but only in four was there concordance between radiological findings
and symptoms of the corresponding joints. The positive predictive value of
radiographic erosions in predicting clinically significant disease was 40%. There
was poor correlation between the presence of radiographic erosions and clinical
signs and symptoms of joint disease.
PMID- 10197455
TI - Granular cell tumor of the subcutis: CT and MRI findings. A report of three
cases.
AB - Three cases of granular cell tumor (GCT) of the subcutis are presented. Computed
tomography showed a mass isodense with muscle with an ill-defined margin.
Magnetic resonance imaging showed a mass with inhomogeneous low signal intensity
on both T1- and T2-weighted-images. Another characteristic feature of
subcutaneous GCT is its attachment in part to muscle. Histological examination
confirmed the diagnosis in all cases.
PMID- 10197456
TI - Endovascular papillary angioendothelioma (Dabska tumor) of bone.
AB - Endovascular papillary angioendothelioma, also known as Dabska tumor, is a rare
vascular neoplasm that usually involves the skin or subcutaneous tissue of
children. There have been no reported cases of this lesion occurring in bone. We
report a Dabska tumor in the distal femur of a 45-year-old woman who, clinically
and radiologically, was felt to have an osteoid osteoma. Histologic study of the
lesion showed a hemangioma with budding fronds of endothelial cells, a feature
characteristic of the Dabska tumor. We feel that the lesion arose in a pre
existing hemangioma, a hypothesis suggested in a few other case reports.
Endovascular papillary angioendothelioma is a low-grade malignant neoplasm,
although only one patient has died due to this lesion. Our patient is
asymptomatic without evidence of recurrence 1 year post curettage.
PMID- 10197457
TI - MRI appearance of clear cell hidradenoma.
AB - We present the first reported MR imaging findings of a histologically proven
clear cell hidradenoma. A fluid level was noted on all pulse sequences in this
lesion, which demonstrated a prominent hemorrhagic component on sectioning. The
presence of an enhancing nodule was also noted, differentiating this lesion from
a post-traumatic hematoma. Fluid levels in a well-defined subcutaneous soft
tissue mass should suggest the possibility of a hidradenoma.
PMID- 10197458
TI - Doppler duplex color localization of osteoid osteomas.
AB - We present two cases of osteoid osteoma in adolescent boys. The lesions were
located in the proximal metaphysis of the right tibia and left femoral diaphysis
respectively. Doppler duplex color study demonstrated clearly the highly vascular
nidus and its feeding artery in one case and only the feeding artery in the
second. We believe these are the first descriptions of osteoid osteomas assessed
with Doppler duplex color, which was also used as guidance for the percutaneous
localization and biopsy.
PMID- 10197459
TI - Parosteal osteosarcoma of a metatarsal with intramedullary invasion.
AB - A 70-year-old man presented with increasing swelling of 2 years' duration, on the
dorsal aspect of the forefoot. Imaging studies revealed a heavily calcified
surface lesion of bone with early invasion of the underlying second metatarsal.
Both imaging findings and the subsequent resection histology were consistent with
a parosteal osteosarcoma, which is particularly rare at this site and at this
age. The differential diagnosis of a mineralizing surface lesion of bone arising
in the foot is discussed.
PMID- 10197461
TI - Unemployment and health.
PMID- 10197460
TI - Digital enlargement in tuberous sclerosis.
AB - A 23-year-old woman with a medical history significant for tuberous sclerosis
presented with symptoms of postpartum endometritis. Focal gigantism of the third
digit of her right hand was incidentally noted and is reported to be a rare
manifestation of tuberous sclerosis.
PMID- 10197462
TI - The ICOH Working Group "Unemployment and Health" Paris 25-26 September 1998: an
introduction. International Commission of Occupational Health.
PMID- 10197463
TI - A multifactorial health risk questionnaire.
AB - OBJECTIVE: to assess the relations between cardiovascular risk factors and
psychological or socio-economic status. METHODS: We used a self-questionnaire
including data upon usual risk factors, anxiety, depression, behavioural pattern,
somatic manifestations, life style, incomes and work-related stress. We gathered
955 people, mainly attending an occupational health examination, filling
anonymously the same restricted questionnaire (83 questions). RESULTS: Non
working people represented only 4.4 per cent of the study group and included
mainly retired people. They differed significantly from wage earners by a higher
level of cardiovascular risk and depression, respectively 15.8 (s.d. 11.3) versus
7.8 (6.7) and 5.6 (3.5) versus 3.9 (2.8). These differences can be related to
older age of this group. Among working people, 30 per cent felt job-insecurity;
they differed significantly from working people by a higher level of anxiety, 8.9
(3.7) versus 7.5 (3.3). There was no difference concerning the absolute
cardiovascular risk or the behavioural pattern. A comprehensive self
questionnaire is proposed.
PMID- 10197464
TI - Occupational health and unemployment in India.
AB - Unemployment is a serious problem in India. Rural workers have no stable and
durable employment. Educated and women experience more unemployment which is a
greater problem in urban than in rural areas. An unemployed takes a long time to
find work and secures it at an inadequate remuneration since job seekers far
outnumber the available opportunities. Unavailability of social security makes
life more difficult for the unemployed. Latest figures place the number of
unemployed at 37.2 million. However, the figure is disputed as no national survey
to determine the extent of unemployment has been undertaken in India. The health
of unemployed has not been an issue. A pilot study was undertaken to assess the
effect of tuberculosis on employment in Delhi. Tuberculosis appeared to be a
significant cause of unemployment and loss of income specially among unskilled
workers. The health and labour ministries may formulate a strategy to promote
research and focus on health protection of unemployed.
PMID- 10197465
TI - Unemployment and health: physicians' role.
AB - Unemployment has been documented to have detrimental impacts on a person's
mental, physical and social well being. When unemployment or being out of work is
due to injury or sickness, the effects are compounded by mental and social
factors. In an effort to prevent prolonged unemployment due to injury or
sickness, changes were made to existing disability income supplement plans to
redirect their focus from basic income support to active employment measures.
This is intended to reduce individual's dependency on financial assistance and
encourage individuals to take personal responsibility for getting back to work.
The various disability insurance plans require primary care physicians to provide
opinion and participate in the recovery and safety return to work of injured or
sick persons. The physician approach to medical care of the injured/sick person
with employment problems should focus on return to work as a goal of treatment.
The patient should be seen as part of a social or environmental system and not as
an isolated individual. The physician has a significant role to play in the
diagnosis, determining functional abilities and participation in the return to
work plan. The physician positive participation, not only provides an intrinsic
cost saving value in insurance costs, but more important, helps patients maintain
gainful employment. Work often helps in regaining health. Many factors are
involved in a return to work outcome and physicians need to know how to identify
and track the factors that facilitate or impede return to work. The challenge for
the physician is to utilize the available resources to facilitate the recovery
and communicate with other parties involved in the return to work process. This
paper discusses the disability insurance plans in Canada and the community
expectations from physicians dealing with patients who are out of work because of
injury or sickness. It is acknowledged that primary care physicians' skills are
not adequate in this area and that there is a need for continuing medical
education to prepare them for this new role. Relevant topics should be introduced
in medical curricula.
PMID- 10197466
TI - Unemployment and mental health in Galicia, Spain.
AB - In our Neuropsychiatric dispensary in Galicia, all 3,000 consultations from June
1997 to May 1998 were summed up. We serve a population of 125,000 living in a
semi-rural district dependent on a strong industrialised city with car, ship and
fishing industry. Of all consulting people, 50% of the 1,000 new ones were
unemployed, and 25% of the 2,000 who came for check-ups. In the group under 25
years of age not having had their first job, main findings were anxiety, stress
migraine, schizoid outbreaks and self-referring delusion. In the group of young
people with unstable jobs, we often found depression, phobias, anorexia/bulimia,
low back pain and functional digestive disorders. Age groups 35-50 showed
depression patterns, hypochondriac symptoms, low back pain and delusion
outbreaks. Those over 50 years old often came from reorganised companies, and
showed hypochondriac or psychosomatic sickness, or they applied for retirement or
sickness benefits.
PMID- 10197467
TI - Unemployment, disguised unemployment, and health: the US case.
PMID- 10197468
TI - Interventions to counteract health effects of unemployment in Germany.
PMID- 10197469
TI - Concept on health promotion about the unemployed in Switzerland.
AB - Unemployment is a relatively new phenomena for Switzerland. Compared with other
countries our unemployment rate of approximately 4% is rather low. Among the
unemployed we found similar health problems as in other countries. The health
situation of the unemployed forces us to take more notice of their problems. In
our federalist country many national, cantonal and local institutions are
treating social and health questions, but no one is responsible for the health
problems of the unemployed, resulting in ineffective interventions. In order to
change this situation we have developed a national concept of health promotion
for the unemployed and are seeking to implement it. Three areas of health
promotion for the unemployed and their families: Services within existing, and if
need, newly created institutions, which can range from counselling to triage and
further referral; Health modules in existing occupational programs and formation
courses as an introduction to the health problems of the unemployed; Special
health courses for the unemployed with in depth treatment of health questions.
Realisation steps of the concept: Sensitisation of the responsible institutions
and persons; Systematic documentation of existing resources and structures;
Elaboration of the course concepts and documents; Carrying out of pilot projects;
Set-up of an infrastructure on the national, cantonal and local level.
PMID- 10197470
TI - Health consequences of unemployment: "Disoccupazione & salute" is a prevention
program at a local level.
PMID- 10197471
TI - Unemployment, labour market policy and health in Sweden during years of crisis in
the 1990's.
AB - OBJECTIVE: To give an overview of an economic crisis in Sweden and its health
consequences for employed and unemployed groups together with some health-related
data from participants in labour market programmes. OUTCOME AND CONCLUSIONS:
During the first half of the 1990's, Sweden was hit by a pervasive crises
characterised by steeply increasing unemployment and growing job insecurity. Long
term survey data show that somatic well-being continued to improve in the
population, while psychological well-being deteriorated, and this deterioration
was of a similar magnitude among unemployed and employed groups. Two non
traditional labour market programmes for unemployed individuals are briefly
described. Both programmes resulted in some positive effects on subjective
health, which, however, were not corroborated by psychophysiological data. It is
argued that the employment-unemployment dichotomy can be replaced by a
dimensional view on labour market connection, as insecure jobs may have as
detrimental health effects as open unemployment. Impediments to empowerment in
the labour market programmes are discussed.
PMID- 10197472
TI - A strategy for health promotion among unemployed people in Japan.
AB - OBJECTIVE: To describe the unemployment situations in Japan and to propose a
strategy for promoting health among unemployed persons. METHODS: The published
government reports and the actual circumstances were analyzed to make an action
program on the basis of social and occupational situations in Japan. RESULTS: The
unemployment rate was low as compared to that of other countries because of two
major reasons. One was that the workers were absorbed in minor or family
corporation despite unsatisfactory job. The other was based on the financial
support system for adjusting employment by the government. In an action program
for promoting health of the unemployed persons, the same health care system as
workers should be applied to the unemployed in the regional center of
occupational health.
PMID- 10197473
TI - For better or for worse? Interventions and mental health consequences of
unemployment.
PMID- 10197474
TI - Routine health check-ups of unemployed in Norway.
AB - In 1994 all the 273 long-term unemployed in the municipality Lillesand, Norway
were invited to participate in a proactive health care program. 229 were included
in the program, consisting of a medical examination by a general practitioner,
councelling, personal support and referrals. The job-loss aroused lots of
negative emotions, mostly defensive feelings and resignations, which are likely
to reduce self-esteem and coping ability. The prevalence of somatoform symptoms
and anxiety was twice as high as in the normal population, and for depression the
prevalence was three times higher. 24% of the unemployed were referred to further
examination. Invitation to a health examination may be the ticket of entry for
revealing some of the concealed morbidity among long-term unemployed. Health
check-ups of unemployed will probably be very cost-effective
PMID- 10197475
TI - Psychological training improves mental health and job-finding among unemployed
people.
AB - The negative psychological effects of unemployment are well documented: lowered
self-esteem and confidence, social isolation, anxiety, depression, reduced life
satisfaction, hopelessness about the future. Further, it has been established
that these effects often prevent re-employment. The need for interventions to
help unemployed people to minimise such psychological effects is clearly
warranted, yet little psychological assistance is usually given. This paper
describes a psychological intervention based on cognitive behavioural therapy
(CBT), the principles of which have been successfully applied through individual
psychotherapy to several psychiatric disorders. We adapted these principles to
create a group-training programme for a non-psychiatric group--long term (>12
months) unemployed. The results demonstrated that significantly more of the CBT
group than the control group improved on measures of mental health, as well as on
success in job-finding: four months after the completion of training 34% of the
CBT group c.f. 12% of the control group had found full-time work. Taking part
time and temporary work into account, these figures increased to 49% (CBT group)
and 28% (control group), indicating the value of psychological interventions in
reducing the negative psychological effects of unemployment, and helping the
unemployed find jobs.
PMID- 10197476
TI - Unemployment and suicidal behaviour in perspective.
PMID- 10197477
TI - A medical report form concerning an examination at job end.
PMID- 10197478
TI - Comparison of lung-function reference values.
AB - OBJECTIVE: Lung-function reference values play an important role in medical
surveillance examinations of occupational and environmental respiratory diseases,
in stipulation of preventive measures, in initiation of therapeutic measures, and
in granting of benefits to which individuals with lung injuries or occupational
lung diseases are entitled (e.g., bronchial asthma, pneumoconiosis, or farmer's
lung disease). Prediction equations most widely used are based on studies
performed more than 20 years ago and may not represent the findings obtained in
today's population. METHODS: We recorded case histories and lung function values
of 139 healthy subjects (spirometric and plethysmographic data, T(LCO)) and
computed the differences of measured values minus predicted ones as recommended
by different authors. RESULTS: The means of these differences can be seen as
shifts in our group versus the theoretical (predicted) values of various authors.
These shifts, the standardized mean values of residuals, and their probability as
determined under the assumptions of the respective regression model and the
number of subjects below the threshold limits are given. FVC, FEV1, and FEV1%FVC
show mostly good agreement with the recommendations by Crapo et al., Roca et al.,
Glindmeyer et al., Brandli et al., and Berger et al. Our IVC and FVC values do
not differ significantly from each other. Normative flow-volume curve parameters
of various authors deviate widely, however, and are not compatible with the
values of our control group. Plethysmographically measured volumes (FRC, TLC, and
RV) are only insufficiently reflected by Quanjer's reference equations. Measured
T(LCO) and K(CO) show good agreement with the predictions of Cotes et al. [11]
for females but display less concurrence with the predictions for males.
CONCLUSIONS: Our results indicate that the ERS values of FVC, FEV1, and FEV1%FVC
mainly applied in Europe should be verified. The much better-evaluated formulas
of Brandli et al. are recommended. Furthermore, the age range between 60 and 70
years should be extrapolated from these formulas until better epidemiological
data on lung function are available.
PMID- 10197479
TI - Occupational exposure to agricultural chemicals: effect on the activities of some
enzymes in the blood of farm workers.
AB - OBJECTIVE: To determine the effect of different durations of exposure to
agricultural chemicals on the activities of the blood enzymes delta
aminolevulinic acid dehydratase (ALAD), superoxide dismutase (SOD), and
cholinesterase (ChE) in tobacco field workers. METHODS: For this preliminary
investigation, 8 volunteers (all smoked tobacco) who were working on a small
tobacco farm were monitored over a period of 2 years along with a comparable
urban unexposed group (n = 4). During the growing season between 1994 and 1996,
dermal and respiratory exposure were determined and blood samples were drawn
after the following durations of field work: (1) preexposure (0 DAY); (2) after 1
day of field work (1 DAY) - workers reentered fields at 24 h after spraying of
acephate and maleic hydrazide; (3) after 30 days of field work (postspraying; 30
DAYS); and (4) Postexposure - no tobacco production. Standard analytical methods
were used. RESULTS: Activity of ALAD was depressed by 30% after 1 DAY and there
was no further decrease in ALAD activity after 30 DAYS of field work. SOD
activity, in contrast, declined by 29% and 50% after 1 DAY and 30 DAYS,
respectively, as compared with 0-DAY activity and that of the urban control,
which was similar to 0-DAY activity (P< or =0.05). Plasma ChE activity declined
by 19% after both 1 and 30 DAYS of exposure/field work. The activities of all
three enzymes were restored to urban control or preexposure levels during
postexposure. Plasma Cd levels were high in the samples taken after 30 DAYS as
compared with the preexposure levels. Respiratory nicotine exposure was highest
after 30 DAYS of field work. CONCLUSION: This preliminary study suggests that
erythrocyte SOD is a sensitive indicator of exposure to agricultural chemicals in
tobacco field workers.
PMID- 10197480
TI - Possible preferential metabolism of xylene isomers following occupational
exposure to mixed xylenes.
AB - OBJECTIVES: Solvent exposures commonly involve mixtures of substances or mixtures
of isomers of a single solvent. These may be metabolised through common pathways,
resulting in the potential for metabolic interactions. These may then lead to
accumulation of solvent or metabolic intermediates, some of which may be toxic.
This paper describes a pilot study conducted to determine the correlation between
airborne xylene isomers and the appearance of methylhippuric acid (MHA) isomers
in urine of workers exposed mainly to xylene. The project also aimed to determine
whether there is preferential metabolism of any isomer by comparison of the
ratios of airborne isomers with the ratios of metabolite isomers appearing in
urine. SUBJECTS AND METHODS: A total of 12 workers (11 male, 1 female) were
recruited into this study, with 2 of the participants providing samples on more
than one occasion. Workers included flooring contractors (5), printers (2),
chemical manufacturers (2), histology technicians (2) and one householder using a
xylene-based varnish. Subjects were aged between 24 and 48 years (37.6+/-2.0
years; mean +/- SEM). After giving informed consent, workers provided a prework
and postwork urine sample on a midweek work day. Samples were stored frozen prior
to analysis. Breathing-zone air samples were collected using personal air
samplers at 50 ml/min. Solvents were trapped on activated-charcoal sampling
tubes. Subjects wore pumps for 18-304 (178+/-24) min on the same day on which
urine samples were collected. RESULTS: Xylene exposures ranged from 1.6 to over
7000 ppm. In all, 7 of 16 measurements exceeded the Australian TWA standard of 80
ppm. Two of the flooring contractors wore respiratory protective equipment (RPE)
and the two histopathology technicians used workplace ventilation systems. Total
urinary MHA output ranged from 10 to 8000 mmol/mol creatinine, with 6 of 16
samples exceeding the modified biological exposure index of 702 mmol/mol.
Correlations between airborne concentrations of individual xylene isomers and
their corresponding MHA isomers were poor but improved when workers using RPE
were excluded from the analysis. Gradients of the regression lines (millimoles of
MHA per mole of creatinine per parts per million of xylene) were 3.2 for o
isomers, 7.0 for p-isomers, and 14.4 for m-isomers. Comparisons of isomer ratios
of xylene in air were made with the corresponding ratio of MHA isomers in urine.
These revealed higher ratios of m-MHA to other MHA isomers than those of m-xylene
to the other xylene isomers. The MHA isomer ratios were expected to be the same
as the airborne xylene isomer ratios if there were no preferential elimination of
any isomer. m-MHA appeared in urine in a greater proportion than would be
predicted from the proportion of m-xylene detected in air. The time course of the
appearance of MHA isomers in urine also suggests that interactions were taking
place, with m-MHA appearing in high proportion in urine following several days of
repeated heavy xylene exposure. On a single moderate exposure, m-MHA appeared
initially in high proportion in the first few hours but was undetectable in urine
after 18 h. p-MHA was detectable for up to 6 h after exposure, and o-MHA remained
detectable after 18 h. CONCLUSIONS: This study suggests that excretion of m-MHA
in urine is favoured over that of the other isomers following exposure to mixed
xylenes. This is independent of airborne xylene isomer composition and suggests
that the metabolism of m-xylene occurs preferentially to that of the other
isomers. It is not clear at which step in the metabolism of xylene this
preference occurs, although other work indicates that the initial oxidation of
xylene to methylbenzyl alcohol by cytochrome P450 2E1 occurs at the same rate for
each isomer. These findings suggest that there is potential for metabolic
interactions between xylene isomers and that these may be the basis for xylene
toxicity.
PMID- 10197481
TI - Characteristics of pain drawings in the neck-shoulder region among the working
population.
AB - OBJECTIVES: The aim was to study the characteristics of pain drawings in the
neck, shoulders, and upper-back regions among the general working population.
METHODS: Pain drawings of the rear view of the neck, shoulders, and upper back
were made by 125 middle-aged subjects from the general working population
suffering from symptoms, mainly ache and pain, in the neck or shoulder regions.
The locations of the markings in each pain drawing were coded to computer files
using a transparent grid (878 pixels). The total area, the number of separate
loci, and the left-right symmetry were recorded. Symptoms and signs were assessed
at a medical examination. RESULTS: The most frequently marked locations in the
resulting aggregated topographical diagram covered two palm-sized areas in the
neck-shoulder angles, with a symmetrical and even distribution occurring between
the left and right sides. Subjects with more chronic or severe symptoms made pain
drawings with larger areas. The presence of tenderness in the neck-trapezius
region was associated with larger areas and more bilateral and multiple loci.
Larger areas with multiple bilateral loci and a more symmetric distribution
characterized pain drawings made by women as compared with those made by men. No
substantial difference was noted in connection with age or educational level.
CONCLUSIONS: Pain drawings of neck and shoulder symptoms among the middle-aged
general working population most usually focused on the neck-shoulder angles with
a symmetrical left-right distribution. The number of separate symptom loci and
their total area, left-right distribution, and symmetry were characteristics
associated with symptom chronicity and severity or signs of tenderness in the
neck-trapezius region.
PMID- 10197482
TI - Application of biological monitoring to the quantitative exposure assessment for
neuropsychological effect by chronic exposure to organic solvents.
AB - OBJECTIVE: Quantitative exposure assessment became more common as a result of
attempts to reduce nondifferential exposure misclassification and to observe a
steeper exposure-response relationship. Several exposure variables were compared
in a demonstration of the exposure-response relationship between
neuropsychological abnormality and long-term exposure to organic solvents in
workers at one shipyard. METHOD: Environmental monitoring and biological
monitoring were performed to evaluate the exposure of the workers to organic
solvents. Cumulative exposure (CE) and lifetime-weighted average exposure
variables were developed with both environmental and biological monitoring data.
A neuropsychological questionnaire and a function test for confirmation of a
disorder or dysfunction in attention, executive function, visuospatial, and
constructional abilities, learning and memory, and psychomotor function were
performed. RESULTS: The abnormal rate in neuropsychological diagnosis was 9.3% in
the exposed group, which was much higher than the 2.1% rate obtained in the
nonexposed group (P<0.01). The neuropsychological abnormal rate showed a
significant dose-response association with CE created with biological monitoring
data. The results also suggest that biological monitoring can provide impressive
and effective information for quantitative exposure assessment, even in
epidemiology studies.
PMID- 10197483
TI - Biological monitoring of occupational exposure to cyclohexane by urinary 1,2- and
1,4-cyclohexanediol determination.
AB - OBJECTIVES: This article reports the results obtained with the biological and
environmental monitoring of occupational exposure to cyclohexane using 1,2
cyclohexanediol (1,2-DIOL) and 1,4-DIOL in urine. The kinetic profile of 1,2-DIOL
in urine suggested by a physiologically based pharmacokinetic (PBPK) model was
compared with the results obtained in workers. METHODS: Individual exposure to
cyclohexane was measured in 156 workers employed in shoe and leather factories.
The biological monitoring of cyclohexane exposure was done by measurement of 1,2
DIOL and 1,4-DIOL in urine collected on different days of the working week. In
all, 29 workers provided urine samples on Monday (before and after the work
shift) and 47 workers provided biological samples on Thursday at the end of the
shift and on Friday morning. Another 86 workers provided biological samples at
the end of the work shift only on Monday or Thursday. RESULTS: Individual
exposure to cyclohexane ranged from 7 to 617 mg/ m3 (geometric mean value 60
mg/m3). Urinary concentrations of 1,2-DIOL (geometric mean) were 3.1, 7.6, 13.2,
and 6.3 mg/g creatinine on Monday (pre- and postshift), Thursday (postshift) and
Friday (pre-shift), respectively. The corresponding values recorded for 1,4-DIOL
were 2.8, 5.1, 7.8, and 3.7 mg/g creatinine. A fairly close, statistically
significant correlation was found between environmental exposure to cyclohexane
and postshift urinary 1,2-DIOL and 1,4-DIOL on Monday. Data collected on Thursday
and Friday showed only a poor correlation to exposure with a wide scatter. Both
metabolites have a urinary half-life of close to 18 h and accumulate during the
working week. CONCLUSIONS: Comparison between data obtained from a PBPK model and
those found in workers suggests that 1,2-DIOL and 1,4-DIOL are urinary
metabolites suitable for the biological monitoring of industrial exposure to
cyclohexane.
PMID- 10197484
TI - No evidence for congenital malformations or prenatal death in infants born to
women with a high dietary intake of fish contaminated with persistent
organochlorines.
AB - OBJECTIVES: The aim of the present study was to assess whether a high dietary
intake of fatty fish from the Baltic Sea, contaminated with persistent
organochlorine compounds, might increase the risk for congenital malformations
and perinatal death. METHODS: A cohort of fishermen's wives from the Swedish east
coast (at the Baltic Sea) were linked to the Swedish Medical Birth Register
(MBR), resulting in the identification of 1501 infants born in the period 1973
1991. A further linkage with the Swedish Registry of Congenital Malformations was
performed. Similar linkages were made for a comparison group of fishermen's wives
from the Swedish west coast, who gave birth to 3553 infants during the study
period. The reproductive end points studied included congenital malformations,
stillbirths, and early neonatal deaths. The expected numbers of these end points
were calculated from the MBR data for the regional populations. RESULTS: In the
east coast cohort, 3.3% of the infants had some malformation diagnosis as
compared with 5.0% of the west coast cohort. As compared with the general
population, somewhat fewer malformations than expected were diagnosed in the east
coast cohort (risk ratio 0.78, 95% CI 0.58-1.04). No specific malformation was
overrepresented in the east coast cohort. The risk ratios for stillbirths and
early neonatal deaths did not significantly differ from unity in any of the
cohorts. CONCLUSIONS: The present results exclude in an unequivocal way an
association between exposure to persistent organochlorines from fatty Baltic Sea
fish and an increased risk for all congenital malformations and perinatal death.
The limited power of the study design, however, does not allow the exclusion of
slight risk excesses for some specific types of malformation.
PMID- 10197485
TI - Seroprevalence of hepatitis A markers in subjects exposed to biological risk.
AB - OBJECTIVES: The seroprevalence of hepatitis A virus antibodies was investigated
in a population of 1051 subjects, of whom 376 were controls and 675 were exposed
to different degrees of biological risk. METHODS: The exposed group was
subdivided into subjects at low (242), intermediate (265), and high (168)
biological hazard; all subjects were employed in the biomedical field. Aspartate
aminotransferase (AST) and alanine aminotransferase (ALT) levels were also
determined. RESULTS: The seroprevalence of positive hepatitis A antibodies was
44.9% in all subjects but was significantly higher in males (50.6%) than in
females (34.2%) and increased according to age (25.9% in subjects aged < or =40
years and 62.2% in subjects aged >40 years). No difference related to exposure to
the biological risk was observed. The prevalence of transaminases at levels above
normal values (chi2 = 4.079, P<0.05 for AST and chi2 = 4.806, P<0.05 for ALT) and
mean values (AST P<0.05; ALT P<0.001) appeared significant in hepatitis A virus
positive subjects. On the other hand, excluding individuals with positive
hepatitis C virus antibodies (16) and positive hepatitis B virus surface antigen
(12), a prevalence of transaminase alterations was not observed, but mean levels
of ALT lasted significantly longer in subjects with positive hepatitis A virus
antibodies (P<0.01). CONCLUSIONS: The results confirm that hepatitis A virus is
not a risk for employees in the biomedical field, but the presence of hepatitis A
virus antibodies suggests a possible, though not clinically evident, liver
involvement.
PMID- 10197486
TI - Dilemma of the natural history of hepatitis C.
PMID- 10197487
TI - Interrelationships of alcohol and iron in liver disease with particular reference
to the iron-binding proteins, ferritin and transferrin.
AB - It is known that the regular consumption of alcohol is responsible for the
disruption of normal iron metabolism in humans, resulting in the excess
deposition of iron in the liver in approximately one-third of alcoholic subjects.
The mechanisms involved are largely unknown; however, it is likely that the two
major proteins of iron metabolism, ferritin and transferrin are intimately
involved in the process. Tissue damage in alcoholic liver disease and the
inherited iron-overload disease, haemochromatosis, are caused by excess alcohol
and iron, respectively. The mechanisms of this damage are believed to be similar
in both disease conditions and involve free radical-mediated toxicity. A high
proportion of haemochromatosis sufferers consume excessive amounts of alcohol and
synergistic hepatotoxic events may occur leading to the earlier development of
liver cirrhosis. This review describes briefly the role of ferritin and
transferrin in normal iron metabolism and in iron overload disease and explores
the possible involvement of these proteins in the pathophysiology of excess iron
deposition in alcoholic subjects.
PMID- 10197488
TI - Carcinoma of the gall-bladder.
AB - Carcinoma of the gall-bladder remains the fifth commonest gastrointestinal
malignancy. Its associations, predisposing factors and epidemiology worldwide are
reviewed in this article. The clinical presentation of carcinoma of the gall
bladder is frequently late, which accounts for the poor prognosis: this is also
discussed. The use of relevant imaging techniques and aggressive management offer
an improved outlook. These important aspects and others, such as the use of
frozen section histology, the risks of trocar seeding and inadequate resection
are mentioned.
PMID- 10197489
TI - Endoscopic variceal ligation for primary prophylaxis of oesophageal variceal
bleed: preliminary report of a randomized controlled trial.
AB - BACKGROUND: Prevention of variceal bleeding, a major cause of morbidity and
mortality, is an important goal in the management of patients with portal
hypertension (PHT). Although propranolol has been found useful in preventing the
first episode of variceal bleeding (primary prophylaxis) in cirrhotic PHT, it has
limitations which include side effects, contraindications, non-compliance and
failure in some patients. Endoscopic variceal ligation (EVL) has not been used
for primary prophylaxis. METHODS: Thirty cirrhotic patients with PHT, grade III
to IV oesophageal varices, hepatic venous pressure gradient > or = 12 mmHg and no
prior history of upper gastrointestinal bleeding were randomized to receive
propranolol (to reduce their pulse rate by 25% from baseline, n = 15) and EVL
(weekly to fortnightly until variceal eradication, n = 15). The two groups were
comparable. All the patients in EVL group had variceal eradication during 3.8 +/-
2.2 sessions. RESULTS: There was no major complication or interval bleeding.
During a follow-up period of 17.6 +/- 4.7 months, varices recurred in three, two
of which bled (successfully treated by EVL). In contrast, during this period of
follow up one patient in the propranolol group had variceal bleeding (P=NS). Side
effects of propranolol included symptomatic bradycardia requiring reduction of
dose in one of 15 patients. CONCLUSIONS: Although sample size in this study is
small, it seems that EVL may be a good option for primary prophylaxis for
variceal bleeding in patients with cirrhotic PHT; further studies on a larger
number of patients and longer follow up are required.
PMID- 10197490
TI - Long-term follow up of a randomized, controlled trial on prophylactic
sclerotherapy of small oesophageal varices in liver cirrhosis.
AB - BACKGROUND: In order to evaluate the prophylactic impact of sclerotherapy of
small varices in patients with cirrhosis and no endoscopic signs suggesting risk
of haemorrhage, a randomized clinical trial was performed. METHODS: Seventy-one
hospitalized patients met the inclusion criteria of diagnosis of cirrhosis with
no previous bleeding and small varices. Due to exclusion criteria of:
gastroduodenal ulcers (n = 5), diverticulosis (n = 1), hepatic insufficiency (n =
10), hepatocellular carcinoma (n = 4), death before randomization (n = 6), age
over 70 (n = 1) and denial of consent to participate in the study (n = 1), 43
patients could be randomized, 21 for sclerotherapy and 22 for the control group.
Two patients (one in each group) were lost to follow up, and another patient,
although not lost, refused sclerotherapy after randomization. Ethanolamine oleate
was used as the sclerosing agent. All patients were followed up for a mean time
of 60 months, initially every 2 months for the first 2 years and clinical and
endoscopic controls were performed each 6-12 months thereafter. RESULTS AND
CONCLUSIONS: During the first 2 years clinical assessment showed that there were
five bleedings in the sclerotherapy group and none in the control group, but
mortality was similar in both groups. Long-term follow up continued to show a
higher prevalence of bleeding in the sclerotherapy group but that mortality was
not different from the control group.
PMID- 10197491
TI - Influence of endoscopic variceal ligation on oesophageal motility.
AB - BACKGROUND: To determine the change of oesophageal manometry in patients with
oesophageal varices before and after oesophageal variceal ligation (EVL).
METHODS: Forty-five patients who had liver cirrhosis and oesophageal varices with
high risk of bleeding were managed by EVL. Oesophageal manometry was performed
just prior to the ligation and 4-6 weeks after obliteration of varices. Another
45 age- and sex-matched patients without hepatic, oesophageal or systemic disease
served as the control group. RESULTS: At 5 cm above the lower oesophageal
sphincter (LES), the amplitude of the contractive wave was significantly lower in
patients before EVL (56.9 +/- 31.8 vs 80.1 +/- 30.1, P< 1.05) and returned to the
level of control subjects after EVL (76.5 +/- 37.0 vs 80.1 +/- 30.1, P> 0.05). At
10 cm above LES, the amplitude of the contractive wave was significantly lower in
patients before and after EVL than the control group (54.3 +/- 29.2 vs 68.1 +/-
29.5, 54.2 +/- 26.0 vs 68.1 +/- 29.5, respectively, P< 0.05). The percentage of
tertiary waves was significantly higher in patients before and after EVL than in
the control group (31.4 +/- 36.6 vs 5.8 +/- 15.1, 26.9 +/- 32.9 vs 5.8 +/- 15.1,
respectively, P< 0.05). However, no significant swallowing disturbance was noted
in patients after EVL. There was significantly greater LES length in patients
before EVL (4.0 +/- 0.9 vs 3.4 +/- 0.7, P<0.05) but there was no significant
difference in the LES length after EVL as compared with the control group. Eighty
six per cent (39/45) of patients developed paraoesophageal varices and 31%
(14/45) developed new varices 6 months after variceal obliteration. However,
there was no significant difference in manometry at the time of variceal
obliteration between patients with variceal recurrence and those without.
CONCLUSIONS: The presence of varices affected oesophageal motility. However, such
abnormality had little clinical significance. Endoscopic variceal ligation
normalized oesophageal motility and may not induce abnormal oesophageal motility.
The manometric change can not be used to predict the recurrence of varices in
cirrhotic patients after variceal obliteration.
PMID- 10197492
TI - Endoscopic variceal ligation is a sufficient procedure for the treatment of
oesophageal varices in patients with hepatitis C liver cirrhosis: comparison with
injection sclerotherapy.
AB - AIMS: Endoscopic variceal ligation (EVL) is a recently developed alternative to
endoscopic injection sclerotherapy (EIS) for the treatment of oesophageal
varices. Endoscopic variceal ligation and EIS were compared in an attempt to
clarify the efficacy and safety of EVL for patients with cirrhosis due to
hepatitis C. METHODS: Endoscopic variceal ligation was performed in 60 patients
and EIS in 30. Varices were eradicated in all patients by EVL and 87% (26 out of
30) by EIS. RESULTS: There was no significant difference between EVL and EIS in
relation to the incidence of bleeding and the 5 year survival rate after
treatment. There were no severe complications except mild substernal pain after
EVL, while pulmonary embolism occurred in one patient receiving EIS. CONCLUSIONS:
Endoscopic variceal ligation is a safe and effective technique for eradicating
oesophageal varices in patients with hepatitis C cirrhosis.
PMID- 10197493
TI - Evaluation of endoscopic variceal ligation in prophylactic therapy for bleeding
of oesophageal varices: a prospective, controlled trial compared with endoscopic
injection sclerotherapy.
AB - BACKGROUND: To evaluate the efficacy of endoscopic variceal ligation (EVL) in
prophylactic therapy for oesophageal varices, we performed a randomized
prospective trial to compare the recurrence of oesophageal varices treated by EVL
with those treated by endoscopic injection sclerotherapy. METHODS: Fifty patients
with liver cirrhosis were divided into two groups at random, after informed
consents were obtained, to receive prophylactic therapy for bleeding of
oesophageal varices. Group 1 patients underwent sessions of sclerotherapy with 5%
ethanolamine oleate used as the sclerosant. Group 2 patients underwent EVL
followed by one or two sessions of sclerotherapy. RESULTS: During the 18 month
follow-up period, both the recurrence rate in group 2 (56%) and the incidence of
bleeding (20%) were significantly higher compared with group 1 (recurrence rate
16%, bleeding 0%). CONCLUSIONS: This result indicates that EVL is not effective
for prophylactic therapy for oesophageal varices in liver cirrhosis.
PMID- 10197494
TI - Clinical evaluation of endoscopic injection sclerotherapy using n-butyl-2
cyanoacrylate for gastric variceal bleeding.
AB - BACKGROUND: Emergency endoscopic injection sclerotherapy (EIS) has been applied
to the initial treatment of gastric variceal bleeding and various methods have
been attempted. METHODS: Emergency EIS was performed on 38 patients with gastric
variceal bleeding using either the ethanolamine oleate (EO) method or n-butyl-2
cyanoacrylate (Histoacryl) method and the outcome was compared. RESULTS: Complete
haemostasis was defined as continuous haemostasis lasting for 14 days or more.
Complete haemostasis was achieved in 52.4% of patients in the EO method versus
100% of those treated with the Histoacryl method, a significant difference,
suggesting that the Histoacryl method was superior for achieving haemostasis in
an emergency. The cumulative non-bleeding rate was also significantly higher in
patients treated with Histoacryl, indicating the durability of haemostasis. There
were no serious complications in patients who received either method of
sclerotherapy. Post-EIS surgery was required in 42.8% of patients treated with
EO, while no surgery was required in those treated with Histoacryl, supporting
the greater haemostatic effect of Histoacryl. Although there was no significant
difference in the cumulative survival rates of patients treated by these two
methods, death from haemorrhage was avoided by using Histoacryl. CONCLUSIONS:
Based on these results, the Histoacryl method is thought to be the initial
treatment of choice for gastric variceal bleeding, because it achieved superior
haemostasis compared with EO and death by haemorrhage was avoided.
PMID- 10197495
TI - Effects of pantoprazole, a novel H+/K+-ATPase inhibitor, on duodenal ulcerogenic
and healing responses in rats: a comparative study with omeprazole and
lansoprazole.
AB - BACKGROUND: Pantoprazole, 2-[(2-pyridylmethyl) sulphinyl] benzimidazole, is a new
substituted benzimidazole that inhibits the parietal cell H+/K+-ATPase. METHODS:
In the present study, the anti-secretory and anti-ulcer activities of
pantoprazole were compared with those of omeprazole and lansoprazole in rats.
RESULTS: Pantoprazole (0.3-3 mg/kg, p.o.) as well as omeprazole (1-10 mg/kg,
p.o.) and lansoprazole (1-10 mg/kg, p.o.) dose-dependently decreased both basal
acid secretion in pylorus-ligated rats and the stimulated acid secretion induced
by mepirizole in acute fistula rats, and the effects of pantoprazole were more
potent than those of omeprazole and lansoprazole, the ED50 values for the
stimulated acid secretion being 0.8, 2.0 and 1.2 mg/kg, respectively. Neither of
these drugs had any effect on duodenal HCO3- secretion. These pump inhibitors
prevented the development of duodenal lesions in response to mepirizole in a dose
related manner, the ED50 values for pantoprazole, omeprazole and lansoprazole
being 0.4, 2.0 and 1.3 mg/kg, respectively. Likewise, pantoprazole showed the
healing promoting action on chronic duodenal ulcers induced by acetic acid, and
this effect was also more potent when compared to omeprazole or lansoprazole.
CONCLUSIONS: We conclude that pantoprazole exhibited both anti-ulcer and healing
promoting effects on duodenal ulcers in rats, and the effects may be attributable
to its potent anti-secretory action. Other pump inhibitors such as omeprazole and
lansoprazole were almost equally effective as pantoprazole, yet this drug was
most potent on the basis of ED50 values.
PMID- 10197496
TI - Isolated gastric tuberculosis of the cardia.
AB - BACKGROUND: Isolated gastric tuberculosis is extremely rare, especially in the
subcardiac region, where the low pH, high motility and absence of lymphoid tissue
result in an unfavourable environment for the development of tuberculous lesions.
METHODS AND RESULTS: Here we present a case of isolated gastric tuberculosis in
the gastric cardia with no evidence of pulmonary involvement. Our patient was a
young man with vague gastrointestinal symptoms and no previous history of
tuberculosis. His condition was first detected on upper endoscopy as a raised
subcardiac ulcer similar in appearance to a submucosal tumour. An endoscopic
forceps biopsy showed the presence of caseating granulomata and acid-fast
bacilli. The lesion resolved completely with 12 months of oral anti-tuberculosis
therapy. CONCLUSIONS: This case illustrates the need for a high index of
suspicion in order to diagnose this rare condition, as it can present in patients
with no particular risk factors or symptoms. Once diagnosed, a complete cure can
often be achieved with a course of oral anti-tuberculosis medication, with
surgery being reserved for severely symptomatic or refractory lesions.
PMID- 10197497
TI - Histological changes during clearance of chronic hepatitis B virus infection by
adoptive immunity transfer.
AB - BACKGROUND: Serological clearance of hepatitis B surface antigen (HBsAg) has been
described after reception of hepatitis B surface antibody positive marrow, via
allogeneic bone marrow transplantation (BMT). Histological changes during the
clearance of HBsAg are unknown. METHODS AND RESULTS: We described two chronic
hepatitis B carriers (both hepatitis B e antigen negative), who cleared HBsAg
after allogeneic bone marrow transplantation. Both received hepatitis B surface
and core antibody positive human leucocyte antigen identical donors' marrow and
had serological clearance of HBsAg 15 and 7 weeks after allogeneic BMT,
respectively. Both events were preceded by hepatic flare. Both patients were also
treated with famciclovir for the prevention of hepatitis B reactivation after
BMT. Histological examination during the flare showed only mild necroinflammatory
activity with multiple foci of confluent necrosis, associated with moderate
lymphocytic infiltration. The majority of these lymphocytes were cluster of
differentiation (CD) 8 positive. Using immunohistochemistry, there was no
detectable hepatic expression of hepatitis B core antigen. However, HBsAg was
positive, mainly in the area of confluent necrosis. Using in situ hybridization,
hepatitis B virus (HBV) DNA was detected in the nucleus of 5% of hepatocytes, but
not in the cytoplasm. CONCLUSIONS: At their last follow up, 22 and 16 months
after BMT, the serum of both patients remained HBsAg negative, hepatitis B
surface antibody positive and HBV-DNA negative by branched DNA assay.
PMID- 10197498
TI - Assessment of long-term outcomes of hepatitis C virus infection in a cohort of
patients with acute hepatitis in 1971-1975: results of a pilot study.
AB - BACKGROUND: To examine the long-term effects of hepatitis C virus (HCV) infection
in a cohort of patients admitted to Fairfield Hospital with hepatitis from 1971
to 1975. The availability of stored sera from this time enabled testing to
identify those who were anti-HCV positive on admission. METHODS: Sixteen per cent
(n = 230) of the cohort tested positive for HCV antibody (anti-HCV). The
'unexposed' group was selected from those who were anti-HCV negative. Systematic
approaches were used to locate the cohort and health outcomes assessed by a study
specific questionnaire and clinical review with repeat serology and liver
function tests. RESULTS: Complete follow up has been achieved on a subset of 35
HCV-seropositive and 70 seronegative individuals. The seropositive group was
significantly more likely to have given a history of injecting drug use, the
presumed route of infection. The seropositive group was also more likely to have
elevated serum alanine aminotransferase levels, but only two (6%) were known to
have progressed to cirrhosis. DISCUSSION: The anti-HCV-positive individuals
followed up to date are at increased risk of liver-related pathology, but few had
progressed to cirrhotic liver disease. This differs from findings of transfusion
related studies and suggests, within the limitations of the study, that the
natural history of community acquired HCV may be more benign.
PMID- 10197499
TI - Discrimination of two different clinical entities, acute-type and subacute-type,
human fulminant hepatitis by peripheral blood lymphocyte subsets.
AB - Human fulminant hepatitis tends to be classified into two groups: acute type (A
FH) and subacute type (S-FH). In order to define these two clinical entities more
precisely, we examined and compared peripheral blood lymphocyte subsets in A-FH
and S-FH patients. We found that S-FH patients had a higher prevalence of CD19+ B
cells (31.1 +/- 7.6% in S-FH vs 12.7 +/- 3.7% in A-FH) and also a lower
prevalence of CD3+T cells (50.2 +/- 8.7% in S-FH vs 65.6 +/- 10.5% in A-FH).
Furthermore, by examining the absolute cell numbers of these subsets, we
determined that their imbalance in S-FH was mainly due to a decrease in CD3+ T
cells. Among several T cell subsets, the CD8+CD11b-T cell subset was elevated in
A-FH and decreased in S-FH (6.1 +/- 2.1% in S-FH, 24.4 +/- 5.8% in A-FH, and 14.8
+/- 7.8% in control). Serial studies of two S-FH patients revealed that the
imbalance of these lymphocyte subsets returned to their proper ratio together
with the improvement of their liver injury. These results indicate that there
might be a different immunological background between A-FH and S-FH.
PMID- 10197500
TI - An unusual cause of rectal bleeding in a patient with cystic fibrosis.
AB - Here we identify a previously unreported cause of rectal bleeding (juvenile
polyposis) in a patient with cystic fibrosis (CF). We believe this patient most
likely has two coexisting genetic diseases. It also raises many issues about
organ transplantation in a patient with medical conditions that individually
increase the risk of gastrointestinal malignancy and stresses the diagnostic
value of endoscopy in CF patients with rectal bleeding.
PMID- 10197501
TI - Patent ductus venosus.
AB - BACKGROUND: Patent ductus venosus is extremely rare with only 14 cases reported
in the world literature. We present a case of patent ductus venosus. METHODS AND
RESULTS: A 29-year-old male was admitted with melaena stool caused by gastric
haemorrhagic ulcers. Laboratory data disclosed severe anaemia; however, liver
function tests were normal. Serum ammonia was also within the normal range.
Serological viral markers for hepatitis B or C were all negative. The abdominal
ultrasonography and computed tomography indicated a 12 mm diameter shunt located
in the left lobe of the liver, which connected the portal vein with the left
hepatic vein. After treatment for gastric ulcers, percutaneous transhepatic
portography was performed and an enormous shunt connecting the umbilical portion
of the portal vein with the left hepatic vein was revealed. CONCLUSIONS:
Histological findings of the liver biopsy showed that portal venules could not be
observed in the portal areas and that no fibrosis or inflammatory cell
infiltration were shown. Because of the anatomical position of the shunt, the
case was diagnosed as patent ductus venosus.
PMID- 10197502
TI - Intra-abdominal angiosarcomatosis after radiotherapy.
AB - BACKGROUND: We report a case of a 61-year-old Japanese woman who developed intra
abdominal angiosarcomatosis 20 years after receiving radiotherapy for squamous
cell carcinoma of the cervix. METHODS AND RESULTS: The surgically resected
portion of the ileum showed diffuse proliferating angiosarcoma, with irregular
channels lined by atypical vascular endothelial cells. Immunohistochemical
studies showed that the tumour cells were positive for Factor VIII-related
antigen and ulex europaeus agglutinin 1. At autopsy, the tumour had disseminated
to the peritoneum and invaded into the right thoracic cavity. CONCLUSIONS: These
findings were compatible with radiation-induced angiosarcomatosis.
PMID- 10197503
TI - Hepatobiliary and pancreatic: right upper quadrant pain.
PMID- 10197504
TI - Gastrointestinal: blue rubber bleb naevus syndrome.
PMID- 10197505
TI - Mitochondria in neurodegeneration: acute ischemia and chronic neurodegenerative
diseases.
PMID- 10197506
TI - The reversible change of GluR2 RNA editing in gerbil hippocampus in course of
ischemic tolerance.
AB - The ischemic tolerance is known to show protective effects on the neurons and the
restricted Ca2+ influx through Ca2+ channels might be involved. In alpha-amino-3
hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor, ribonucleic acid
(RNA) editing of the GluR2 subunit determines receptor desensitization and Ca2+
permeability. The authors investigated the effect of ischemic tolerance on the
messenger RNA editing of Q/R and R/G sites of GluR2 subunit in hippocampus. It
was found that the rate of RNA editing in Q/R site showed no change (100%
edited), whereas that in R/G site decreased significantly (83.3% normal editing
level to 60.4%) at day 3 (preconditioning period) and returned to normal level at
day 14 (after preconditioning period). Further investigation revealed that the
decrease of editing rate in ischemic tolerance resulted mainly from the decrease
of editing in CA1 area.
PMID- 10197507
TI - Spatial assessment of the dynamics of lactate formation in focal ischemic rat
brain.
AB - Early identification of the potentially salvageable penumbra is critical for the
determination of therapeutic intervention strategies in acute focal cerebral
ischemia. This study differentiates the ischemic penumbra from the core on the
basis of the dynamics of lactate formation. This was tested in a rat model of
focal cerebral ischemia by infusion of [1-13C]-glucose, using lactate-edited
magnetic resonance spectroscopic imaging techniques. The authors detected
essentially no enrichment of lactate with 13C-label from the infused 13C-glucose
in the ischemic core. However, in borderzone areas, 13C was incorporated into
lactate, which could point toward compromised but potentially viable tissue. The
authors' findings suggest that this combination of 13C-glucose infusion with the
proposed magnetic resonance methods may aid in differentiating the penumbra from
the core in cerebral ischemia.
PMID- 10197508
TI - Rapid efflux of lactate from cerebral cortex during K+ -induced spreading
cortical depression.
AB - Rapid transport of lactate from activated brain regions to blood, perhaps
reflecting enhanced metabolite trafficking, would prevent local trapping of
labeled metabolites of [6-14C]glucose and cause underestimation of calculated
CMRglc. Because the identities of glucose metabolites lost from activated
structures and major routes of their removal are not known, arteriovenous
differences across brains of conscious normoxic rats for derivatives of [6
14C]glucose were determined under steady-state conditions in blood during K+
induced spreading cortical depression. Lactate was identified as the major
labeled product lost from brain. Its entry to blood was detected within 2 minutes
after a pulse of [6-14C]glucose, and it accounted for 96% of the 14C lost from
brain within approximately 8 minutes. Lactate efflux corresponded to 20% of
glucose influx, but accounted for only half the magnitude of underestimation of
CMRglc when [14C]glucose is the tracer, suggesting extensive [14C]lactate
trafficking within brain. [14C]Lactate spreading within brain is consistent with
(1) relatively uniform pattern labeling of K+ -treated cerebral cortex by [6
14C]glucose contrasting heterogeneous labeling by [14C]deoxyglucose, and (2)
transport of 14C-labeled lactate and inulin up to 1.5 and 2.4 mm, respectively,
within 10 minutes. Thus, newly synthesized lactate exported from activated cells
rapidly flows to blood and probably other brain structures.
PMID- 10197509
TI - Cerebral oxygen/glucose ratio is low during sensory stimulation and rises above
normal during recovery: excess glucose consumption during stimulation is not
accounted for by lactate efflux from or accumulation in brain tissue.
AB - Functional activation stimulates CMRglc more than CMRO2 and raises lactate levels
in brain. This has been interpreted as evidence that brain work is supported
mainly by energy derived from anaerobic glycolysis. To determine if lactate
production accounts for the "excess" glucose consumption, cerebral arteriovenous
differences were measured in conscious rats before, during, and 15 minutes after
sensory stimulation; the brains were rapidly frozen in situ immediately after
completion of blood sampling and assayed for metabolite levels. The molar
O2/glucose uptake ratio fell from 6.1+/-1.1 (mean+/-SD) before stimulation to
5.0+/-1.1 during activation (P<0.01); lactate efflux from brain to blood was
detectable at rest but not during stimulation. By 15 minutes after activation, O2
and lactate arteriovenous differences normalized, whereas that for glucose fell,
causing the O2/glucose ratio to rise above preactivation levels to 7.7+/-2.6
(P<0.01). Brain glucose levels remained stable through all stages of activity.
Brain lactate levels nearly doubled during stimulation but normalized within 15
minutes of recovery. Brain glycogen content fell during activation and declined
further during recovery. These results indicate that brain glucose metabolism is
not in a steady state during and shortly after activation. Furthermore, efflux
from and increased content of lactate in the brain tissue accounted for less than
54% of the "excess" glucose used during stimulation, indicating that a shift to
anaerobic glycolysis does not fully explain the disproportionately greater
increases in CMRglc above that of CMRO2 in functionally activated brain. These
results also suggest that the apparent dissociation between glucose utilization
and O2 consumption during functional activation reflects only a temporal
displacement; during activation, glycolysis increases more than oxidative
metabolism, leading to accumulation of products in intermediary metabolic pools
that are subsequently consumed and oxidized during recovery.
PMID- 10197510
TI - Metabolic activity patterns in the monkey visual cortex as revealed by spectral
analysis.
AB - The metabolic activity pattern of the monkey visual cortex was mapped
quantitatively with [14C]-2-deoxyglucose during the performance of a visually
guided reaching task. After bandpass filtering of the reconstructed two
dimensional metabolic maps of areas V1 and V2, alternating bands of high and low
metabolic activity were apparent in control and experimental hemispheres. The
spatial arrangement of active bands was studied with two-dimensional spectral
analysis, and bands were found to be more organized in the experimental monkey.
In area V1 of the control monkey the spectral amplitude was spread over a wider
range of directions and frequencies than in the experimental subject. The finding
that layer IV is characterized by more complex spectra than layers I through III
suggests the coexistence of more than one active columnar system in the
geniculorecipient layer. In area V2, stripes running almost perpendicular to the
V1/V2 border were found along with superimposed patches of enhanced metabolic
activity. In the experimental hemispheres, the corresponding spectra were
extremely sharp yielding a constant periodicity. It is suggested that the well
organized columnar arrangement within areas V1 and V2 of the experimental
hemispheres emerges from the diffusely organized background network of activity
patterns in the control state.
PMID- 10197511
TI - Platelet-activating factor mediates ischemia-induced leukocyte-endothelial
adherence in newborn pig brain.
AB - The authors examined the involvement of platelet-activating factor (PAF) in
mediating leukocyte adherence to brain postcapillary pial venules and altering
blood-brain barrier (BBB) permeability during basal conditions and during
reoxygenation after asphyxia in newborn piglets. Intravital epifluorescence
videomicroscopy, closed cranial windows, and labeling of leukocytes with
rhodamine 6G allowed us to obtain serial measurements of adherent leukocytes
within postcapillary venules. Blood-brain barrier breakdown was determined by
optical measures of cortical extravascular fluorescence intensity after
intravenous sodium fluorescein. Superfusion of PAF over the cortex induced a dose
dependent increase in leukocyte adherence to cerebral venules and leakage of
fluorescein; with 1 micromol/L PAF, the magnitude of adherence and BBB breakdown
was similar to that seen during reoxygenation after 9 minutes of asphyxia. Both
adherence and loss of BBB integrity resulting from either exogenous PAF or
asphyxia-reoxygenation could be significantly attenuated by intravenous
administration of WEB 2086, a PAF receptor antagonist. Window superfusion of
superoxide dismutase with PAF attenuated PAF-induced increases in adherence and
associated fluorescein leakage. These findings indicate that PAF exhibits
proinflammatory effects in piglet brain and that PAF contributes to leukocyte
adherence and BBB breakdown after cerebral ischemia. These PAF effects are
mediated by increases in superoxide radical generation.
PMID- 10197512
TI - Upregulation of MAP1B and MAP2 in the rat brain after middle cerebral artery
occlusion: effect of age.
AB - Although stroke in humans usually afflicts the elderly, most experimental studies
on the nature of cerebral ischemia have used young animals. This is especially
important when studying restorative processes that are age dependent. To explore
the potential of older animals to initiate regenerative processes after cerebral
ischemia, the authors studied the expression of the juvenile-specific
cytoskeletal protein, microtubule-associated protein (MAP) 1B, and the adult
specific protein, MAP2, in male Sprague-Dawley rats at 3 months and 20 months of
age. The levels of MAP1B and MAP2 transcripts and the corresponding proteins
declined with increasing age in the hippocampus. In the cortex, the levels of the
transcripts did not change significantly with age, but the morphologic features
of immunostained fibers were clearly affected by age; that is, cortical MAP1B
fibers became thicker, and MAP2 fibers, more diffuse, in aged rats. Focal
cerebral ischemia, produced by reversible occlusion of the right middle cerebral
artery, resulted in a large decrease in the expression of both MAP1B and MAP2 in
the infarct core at the messenger ribonucleic acid and protein levels. However,
at 1 week after the stroke, there was vigorous expression of MAP1B and its
messenger ribonucleic acid, as well as MAP2 protein, in the border zone adjacent
to the infarct of 3-month-old and 20 month-old male Sprague-Dawley rats. The
upregulation of these key cytologic elements generally was diminished in aged
rats compared with young animals, although the morphologic features of fibers in
the infarct border zone were similar in both age groups. These results suggest
that the regenerative potential of the aged rat brain appears to be competent,
although attenuated, at least with respect to MAP1B and MAP2 expression up to 20
months of age.
PMID- 10197513
TI - Altered expression levels of SEF-2 and p112 in the rat hippocampus after
transient cerebral ischemia: identification by mRNA differential display.
AB - The authors used mRNA differential display to identify genes whose expression
levels are altered in the adult rat hippocampus 24 hours after global ischemia.
At this time after challenge, the basic helix-loop-helix transcription factor,
SEF-2, and the 26S proteasome complex subunit, p112, were identified as genes
whose expression levels are decreased and increased, respectively, in the
hippocampus. To determine the spatial and temporal patterns of expression change
for each gene, the authors antisense in situ hybridization to paired brain
sections of sham-operated and global ischemia-challenged rats at 6, 12, and 24
hours after reperfusion SEF-2 expression was not significantly altered from that
of sham-operated controls in any hippocampal subfield at or before 12 hours after
challenge. At 24 hours after ischemia, however, SEF-2 expression levels were
significantly diminished in the vulnerable CA1 subfield, but not in the less
vulnerable CA3 or dentate granule cell subfields. The proteasome p112 subunit
gene displayed no change in expression levels at 6 hours after insult; however,
an elevated expression was observed at 12 hours after challenge in the dentate
granule cell subfield. By 24 hours after challenge, p112 expression was
significantly elevated in both the CA1 and dentate granule cell subfields. These
results demonstrate that a member of the basic helix-loop-helix family of
transcription factors, SEF-2, and the major subunit of the 26S proteasome
complex, p112, display altered gene expression in the hippocampus after transient
cerebral ischemia.
PMID- 10197514
TI - An intrathecal bolus of cyclosporin A before injury preserves mitochondrial
integrity and attenuates axonal disruption in traumatic brain injury.
AB - Traumatic brain injury evokes multiple axonal pathologies that contribute to the
ultimate disconnection of injured axons. In severe traumatic brain injury, the
axolemma is perturbed focally, presumably allowing for the influx of Ca2+ and
initiation of Ca2+ -sensitive, proaxotomy processes. Mitochondria in foci of
axolemmal failure may act as Ca2+ sinks that sequester Ca2+ to preserve low
cytoplasmic calcium concentrations. This Ca2+ load within mitochondria, however,
may cause colloid osmotic swelling and loss of function by a Ca2+ -induced
opening of the permeability transition pore. Local failure of mitochondria, in
turn, can decrease production of high-energy phosphates necessary to maintain
membrane pumps and restore ionic balance in foci of axolemmal permeability
change. The authors evaluated the ability of the permeability transition pore
inhibitor cyclosporin A (CsA) to prevent mitochondrial swelling in injured axonal
segments demonstrating altered axolemmal permeability after impact acceleration
injury in rat. At the electron microscopic level, statistically fewer abnormal
mitochondria were seen in traumatically injured axons from CsA-pretreated injured
animals. Further, this mitochondrial protection translated into axonal protection
in a second group of injured rats, whose brains were reacted with antibodies
against amyloid precursor protein, a known marker of injured axons. Pretreatment
with CsA significantly reduced the number of axons undergoing delayed axotomy, as
evidenced by a decrease in the density of amyloid precursor protein
immunoreactive axons. Collectively, these studies demonstrate that CsA protects
both mitochondria and the related axonal shaft, suggesting that this agent may be
of therapeutic use in traumatic brain injury.
PMID- 10197515
TI - Oscillations in cerebral blood flow detected with a transcranial Doppler index.
AB - Although transcranial Doppler ultrasound (TCD) has been used to detect
oscillations in CBF, interpretation is severely limited, since only blood
velocity and not flow is measured. Oscillations in vessel diameter could,
therefore, mask or alter the detection of those in flow by TCD velocities. In
this report, the authors use a TCD-derived index of flow to detect and quantify
oscillations of CBF in humans at rest. A flow index (FI) was calculated from TCD
spectra by averaging the intensity weighted mean in a beat-by-beat manner over 10
seconds. Both FI and TCD velocity were measured in 16 studies of eight normal
subjects at rest every 10 seconds for 20 minutes. End tidal CO2 and blood
pressure were obtained simultaneously in six of these studies. The TCD probe
position was meticulously held constant. An index of vessel area was calculated
by dividing FI by velocity. Spectral estimations were obtained using the Welch
method. Spectral peaks were defined as peaks greater than 2 dB above background.
The frequencies and magnitudes of spectral peaks of FI, velocity, blood pressure,
and CO2 were compared with t tests. The Kolmogorov-Smirnov test was used to
further confirm that the data were not white noise. In most cases, three spectral
peaks (a, b, c) could be identified, corresponding to periods of 208+/-93, 59+/
31, and 28+/-4 (SD) seconds for FI, and 196+/-83, 57+/-20, and 28+/-6, (SD)
seconds for velocity. The magnitudes of the spectral peaks for FI were
significantly greater (P<0.02) than those for velocity. These magnitudes
corresponded to variations of at least 15.6%, 9.8%, and 6.8% for FI, and 4.8%,
4.2%, and 2.8% for velocity. The frequencies of the spectral peaks of CO2 were
similar to those of FI with periods of 213+/-100, 60+/-46, and 28+/-3.6 (SD)
seconds. However, the CO2 spectral peak magnitudes were small, with an estimated
maximal effect on CBF of (+/-) 2.5+/-0.98, 1.5+/-0.54, and 1.1+/-0.31 (SD)
percent. The frequencies of the blood pressure spectral peaks also were similar,
with periods of 173+/-81, 44+/-8, and 26+/-2.5 (SD) seconds. Their magnitudes
were small, corresponding to variations in blood pressure of (+/-) 2.1+/-0.55,
0.97+/-0.25, and 0.72+/-0.19 (SD) percent. Furthermore, coherence analysis showed
no correlation between CO2 and FI, and only weak correlations at isolated
frequencies between CO2 and velocity, blood pressure and velocity, or blood
pressure and FI. The Kolmogorov-Smirnov test distinguished our data from white
noise in most cases. Oscillations in vessel flow occur with significant magnitude
at three distinct frequencies in normal subjects at rest and can be detected with
a TCD-derived index. The presence of oscillations in blood velocity at similar
frequencies but at lower magnitudes suggests that the vessel diameters oscillate
in synchrony with flow. Observed variations in CO2 and blood pressure do not
explain the flow oscillations. Ordinary TCD velocities severely underestimate
these oscillations and so are not appropriate when small changes in flow are to
be measured.
PMID- 10197516
TI - Transfer function analysis of cerebral hemodynamics in patients with carotid
stenosis.
AB - This study evaluates the validity of the transfer function analysis of
spontaneous fluctuations of arterial blood pressure (ABP) and blood flow velocity
of the middle cerebral artery (MCAFV) as a simple, convenient method to assess
human cerebral autoregulation in patients with carotid stenosis. Eighty-three
consecutive patients with various degrees of carotid stenosis and 37 healthy
controls were enrolled. The carotid stenosis was graded based on the diagnostic
criteria of duplex ultrasound. Instantaneous bilateral MCAFV and ABP of all
participants were assessed noninvasively using transcranial Doppler sonography
and the servocontrolled infrared finger plethysmography, respectively. Spectral
analyses of ABP and MCAFV were performed by fast Fourier transform. The
fluctuations in ABP as well as in MCAFV were diffracted into three components at
specific frequency ranges designated as high-frequency (HF; 0.15 to 0.4 Hz), low
frequency (LF; 0.04 to 0.15 Hz), and very low-frequency (VLF; 0.016 to 0.04 Hz).
Cross-spectral analysis was applied to quantify the coherence, transfer phase,
and magnitude in individual HF, LF, and VLF components. Transcranial Doppler CO2
vasomotor reactivity was measured with 5% CO2 inhalation. The LF phase angle (r=
0.53, P<0.001); magnitude of VLF (r=-0.29, P=0.002), LF (r=-0.35, P<0.001), and
HF (r=-0.47, P<0.001); and CO2 vasomotor reactivity (r=-0.66, P<0.001) were
negatively correlated with the severity of stenosis. Patients with unilateral
high-grade (greater than 90% stenosis) carotid stenosis demonstrated significant
reduction in LF phase angle (P<0.001) and HF magnitude (P=0.018) on the
ipsilateral side of the affected vessel compared with their contralateral side.
The study also revealed a high sensitivity, specificity, and accuracy using LF
phase angle and HF magnitude to detect a high-grade carotid stenosis. A strong
correlation existed between the LF phase angle and the CO2 vasomotor reactivity
test (r=0.62, P<0.001), and the correlation between the HF magnitude and the CO2
vasomotor reactivity (r=0.44, P<0.001) was statistically significant as well. We
conclude that transfer function analysis of spontaneous fluctuations of MCAFV and
ABP could be used to identify hemodynamically significant high-grade carotid
stenosis with impaired cerebral autoregulation or vasomotor reserve.
PMID- 10197517
TI - Sorting out receptor trafficking.
PMID- 10197518
TI - Trying versus succeeding: event-related designs dissociate memory processes.
PMID- 10197519
TI - How hallucinations make themselves heard.
PMID- 10197520
TI - Harm's way: polyglutamine repeats and the activation of an apoptotic pathway.
PMID- 10197521
TI - From membrane to cytoskeleton: enabling a connection.
PMID- 10197522
TI - Braking news: calcium in the growth cone.
PMID- 10197523
TI - Synaptic [Ca2+]: intracellular stores spill their guts.
PMID- 10197524
TI - From fruit flies to barnacles, histamine is the neurotransmitter of arthropod
photoreceptors.
PMID- 10197525
TI - The neural code of the retina.
PMID- 10197526
TI - Mosaic analysis with a repressible cell marker for studies of gene function in
neuronal morphogenesis.
AB - We describe a genetic mosaic system in Drosophila, in which a dominant repressor
of a cell marker is placed in trans to a mutant gene of interest. Mitotic
recombination events between homologous chromosomes generate homozygous mutant
cells, which are exclusively labeled due to loss of the repressor. Using this
system, we are able to visualize axonal projections and dendritic elaboration in
large neuroblast clones and single neuron clones with a membrane-targeted GFP
marker. This new method allows for the study of gene functions in neuroblast
proliferation, axon guidance, and dendritic elaboration in the complex central
nervous system. As an example, we show that the short stop gene is required in
mushroom body neurons for the extension and guidance of their axons.
PMID- 10197527
TI - Slit2-Mediated chemorepulsion and collapse of developing forebrain axons.
AB - Diffusible chemorepellents play a major role in guiding developing axons toward
their correct targets by preventing them from entering or steering them away from
certain regions. Genetic studies in Drosophila revealed a novel repulsive
guidance system that prevents inappropriate axons from crossing the CNS midline;
this repulsive system is mediated by the Roundabout (Robo) receptor and its
secreted ligand Slit. In rodents, Robo and Slit are expressed in the spinal cord
and Slit can repel spinal motor axons in vitro. Here, we extend these findings
into higher brain centers by showing that Robo1 and Robo2, as well as Slit1 and
Slit2, are often expressed in complementary patterns in the developing forebrain.
Furthermore, we show that human Slit2 can repel olfactory and hippocampal axons
and collapse their growth cones.
PMID- 10197528
TI - F-Spondin, expressed in somite regions avoided by neural crest cells, mediates
inhibition of distinct somite domains to neural crest migration.
AB - Neural crest (NC) cells migrate exclusively into the rostral half of each
sclerotome, where they avoid the dermomyotome and the paranotochordal sclerotome.
F-spondin is expressed in these inhibitory regions and throughout the caudal
halves. In vitro bioassays of NC spreading on substrates of rostral or caudal
epithelial-half somites (RS or CS, respectively) revealed that NC cells adopt on
RS a fibroblastic morphology, whereas on CS they fail to flatten. F-spondin
inhibited flattening of NC cells on RS. Conversely, F-spondin antibodies
prevented rounding up of NC cells on CS. Addition of F-spondin to trunk explants
inhibited NC migration into the sclerotome, and treatment of embryos with anti-F
spondin antibodies yielded migration into otherwise inhibitory sites. Thus,
somite-derived F-spondin is an inhibitory signal involved in patterning the
segmental migration of NC cells and their topographical segregation within the
RS.
PMID- 10197529
TI - Neurexins are functional alpha-latrotoxin receptors.
AB - Alpha-latrotoxin is a potent neurotoxin that triggers synaptic exocytosis.
Surprisingly, two distinct neuronal receptors for alpha-latrotoxin have been
described: CIRL/latrophilin 1 (CL1) and neurexin-1alpha. Alpha-latrotoxin is
thought to trigger exocytosis by binding to CL1, while the role of neurexin
1alpha is uncertain. Using PC12 cells, we now demonstrate that neurexins indeed
function as alpha-latrotoxin receptors that are at least as potent as CL1. Both
alpha- and beta-neurexins represent autonomous alpha-latrotoxin receptors that
are regulated by alternative splicing. Similar to CL1, truncated neurexins
without intracellular sequences are fully active; therefore, neurexins and CL1
recruit alpha-latrotoxin but are not themselves involved in exocytosis. Thus,
alpha-latrotoxin is unique among neurotoxins, because it utilizes two unrelated
receptors, probably to amplify recruitment of alpha-latrotoxin to active sites.
PMID- 10197530
TI - Synaptic targeting of the postsynaptic density protein PSD-95 mediated by lipid
and protein motifs.
AB - During synaptic development, proteins aggregate at specialized pre- and
postsynaptic structures. Mechanisms that mediate protein clustering at these
sites remain unknown. To investigate this process, we analyzed synaptic targeting
of a postsynaptic density protein, PSD-95, by expressing green fluorescent
protein- (GFP-) tagged PSD-95 in cultured hippocampal neurons. We find that
postsynaptic clustering relies on three elements of PSD-95: N-terminal
palmitoylation, the first two PDZ domains, and a C-terminal targeting motif. In
contrast, disruptions of PDZ3, SH3, or guanylate kinase (GK) domains do not
affect synaptic targeting. Palmitoylation is sufficient to target the diffusely
expressed SAP-97 to synapses, and palmitoylation cannot be replaced with
alternative membrane association motifs, suggesting that a specialized synaptic
lipid environment mediates postsynaptic clustering. The requirements for PDZ
domains and a C-terminal domain of PSD-95 indicate that protein-protein
interactions cooperate with lipid interactions in synaptic targeting.
PMID- 10197531
TI - EphrinB ligands recruit GRIP family PDZ adaptor proteins into raft membrane
microdomains.
AB - Transmembrane ephrinB proteins have important functions during embryonic
patterning as ligands for Eph receptor tyrosine kinases and presumably as signal
transducing receptor-like molecules. Consistent with "reverse" signaling,
ephrinB1 is localized in sphingo-lipid/cholesterol-enriched raft microdomains,
platforms for the localized concentration and activation of signaling molecules.
Glutamate receptor-interacting protein (GRIP) and a highly related protein, which
we have termed GRIP2, are recruited into these rafts through association with the
C-terminal PDZ target site of ephrinB1. Stimulation of ephrinB1 with soluble
EphB2 receptor ectodomain causes the formation of large raft patches that also
contain GRIP proteins. Moreover, a GRIP-associated serine/threonine kinase
activity is recruited into ephrinB1-GRIP complexes. Our findings suggest that
GRIP proteins provide a scaffold for the assembly of a multiprotein signaling
complex downstream of ephrinB ligands.
PMID- 10197532
TI - Axon/dendrite targeting of metabotropic glutamate receptors by their cytoplasmic
carboxy-terminal domains.
AB - The subcellular targeting of neurotransmitter receptors is vital in controlling
polarized information flow in the brain. We show here that metabotropic glutamate
receptors are differentially targeted when expressed from defective viral vectors
in cultured hippocampal neurons; mGluR1a and mGluR2 are targeted to dendrites and
excluded from axons, whereas mGluR7 is targeted to axons and dendrites. Chimeras
and deletions revealed that axon exclusion of mGluR2 versus axon targeting of
mGluR7 is mediated by their 60 amino acid C-terminal cytoplasmic domains.
Addition of the mGluR7 C-terminal sequence to mGluR2 or to the unrelated
somatodendritic protein telencephalin (tln) induced axon targeting, indicating
dominance of the axonal signal. These mGluR sorting signals represent novel
plasma membrane axon/dendrite targeting signals.
PMID- 10197533
TI - A new ER trafficking signal regulates the subunit stoichiometry of plasma
membrane K(ATP) channels.
AB - Proper ion channel function often requires specific combinations of pore-forming
alpha and regulatory beta subunits, but little is known about the mechanisms that
regulate the surface expression of different channel combinations. Our studies of
ATP-sensitive K+ channel (K(ATP)) trafficking reveal an essential quality control
function for a trafficking motif present in each of the alpha (Kir6.1/2) and beta
(SUR1) subunits of the K(ATP) complex. We show that this novel motif for
endoplasmic reticulum (ER) retention/retrieval is required at multiple stages of
K(ATP) assembly to restrict surface expression to fully assembled and correctly
regulated octameric channels. We conclude that exposure of a three amino acid
motif (RKR) can explain how assembly of an ion channel complex is coupled to
intracellular trafficking.
PMID- 10197534
TI - Calmodulin is the Ca2+ sensor for Ca2+ -dependent inactivation of L-type calcium
channels.
AB - Elevated intracellular Ca2+ triggers inactivation of L-type calcium channels,
providing negative Ca2+ feedback in many cells. Ca2+ binding to the main alpha1c
channel subunit has been widely proposed to initiate such Ca2+ -dependent
inactivation. Here, we find that overexpression of mutant, Ca2+ -insensitive
calmodulin (CaM) ablates Ca2+ -dependent inactivation in a "dominant-negative"
manner. This result demonstrates that CaM is the actual Ca2+ sensor for
inactivation and suggests that CaM is constitutively tethered to the channel
complex. Inactivation is likely to occur via Ca2+ -dependent interaction of
tethered CaM with an IQ-like motif on the carboxyl tail of alpha1c. CaM also
binds to analogous IQ regions of N-, P/Q-, and R-type calcium channels,
suggesting that CaM-mediated effects may be widespread in the calcium channel
family.
PMID- 10197535
TI - NMDAR channel segments forming the extracellular vestibule inferred from the
accessibility of substituted cysteines.
AB - In NMDA receptor channels, the M2 loop forms the narrow constriction and the
cytoplasmic vestibule. The identity of an extracellular vestibule leading toward
the constriction remained unresolved. Using the substituted cysteine
accessibility method (SCAM), we identified channel-lining residues of the NR1
subunit in the region preceding M1 (preM1), the C-terminal part of M3 (M3C), and
the N-terminal part of M4 (M4N). These residues are located on the extracellular
side of the constriction and, with one exception, are exposed to the pore
independently of channel activation, suggesting that the gate is at the
constriction or further cytoplasmic to it. Permeation of Ca2+ ions was decreased
by mutations in M3C and M4N, but not by mutations in preM1, suggesting a
functionally distinct contribution of the segments to the extracellular vestibule
of the NMDA receptor channel.
PMID- 10197536
TI - Architecture of a K+ channel inner pore revealed by stoichiometric covalent
modification.
AB - Inwardly rectifying K+ channels bind intracellular magnesium and polyamines to
generate inward rectification. We have examined the architecture of the inner
pore of Kir2.1 channels by covalently attaching a constrained number (from one to
four) of positively charged moieties of different sizes to the channel. Our
results indicate that the inner pore is formed solely by the second transmembrane
segment and is unprecedentedly wide. At a position critical for inward
rectification (D172), the pore is sufficiently wide to bind three Mg2+ ions or
polyamine molecules simultaneously. Single-channel recordings directly
demonstrate that partially modified channels exhibit distinct subconductance
levels. Such a wide inner pore may greatly facilitate ion permeation and high
affinity binding of multiple pore blockers to generate strong inward
rectification.
PMID- 10197537
TI - Increased exploratory activity and altered response to LSD in mice lacking the 5
HT(5A) receptor.
AB - In order to determine the distribution and function of the 5-HT5A serotonin
receptor subtype, we generated knockout mice lacking the 5-HT5A gene. Comparative
autoradiography studies of brains of wild-type (wt) and 5-HT5A knockout (5A-KO)
mice revealed the existence of binding sites with high affinity for [125I]LSD
that correspond to 5-HT5A receptors and that are concentrated in the olfactory
bulb, neocortex, and medial habenula. When exposed to novel environments, the 5A
KO mice displayed increased exploratory activity but no change in anxiety-related
behaviors. In addition, the stimulatory effect of LSD on exploratory activity was
attenuated in 5A-KO mice. These results suggest that 5-HT5A receptors modulate
the activity of neural circuits involved specifically in exploratory behavior and
suggest that some of the psychotropic effects of LSD may be mediated by 5-HT5A
receptors.
PMID- 10197538
TI - Attention modulates contextual influences in the primary visual cortex of alert
monkeys.
AB - The response properties of cells in the primary visual cortex (V1) were measured
while the animals directed their attention either to the position of the neuron's
receptive field (RF), to a position away from the RF (focal attention), or to
four locations in the visual field (distributed attention). Over the population,
varying attentional state had no significant effect on the response to an
isolated stimulus within the RF but had a large influence on the facilitatory
effects of contextual lines. We propose that the attentional modulation of
contextual effects represents a gating of long range horizontal connections
within area V1 by feedback connections to V1 and that this gating provides a
mechanism for shaping responses under attention to stimulus configuration.
PMID- 10197539
TI - Frontal brain potentials during recognition are modulated by requirements to
retrieve perceptual detail.
AB - To assess the role of prefrontal cortex in retrieval and address the controversy
about whether prefrontal retrieval operations are engaged only following
successful retrieval, we recorded event-related brain potentials during two
recognition tests with differing demands on retrieval effort. Both tests included
object drawings that were (1) identical to those studied, (2) the same but with
altered aspect ratios, and (3) previously unseen. Instructions were to respond
"old" only if drawings were not modified (specific test) or regardless of
modifications (general test). Frontal potentials were enhanced during the
specific relative to the general test for all three types of drawings. We
conclude that these potentials reflected differential engagement of strategic
retrieval, that this function relied on left prefrontal cortex, and that it was
not contingent on successful retrieval.
PMID- 10197540
TI - Activation of Heschl's gyrus during auditory hallucinations.
AB - Apart from being a common feature of mental illness, auditory hallucinations
provide an intriguing model for the study of internally generated sensory
perceptions that are attributed to external sources. Until now, the knowledge
about the cortical network that supports such hallucinations has been restricted
by methodological limitations. Here, we describe an experiment with paranoid
schizophrenic patients whose on- and offset of auditory hallucinations could be
monitored within one functional magnetic resonance imaging (fMRI) session. We
demonstrate an increase of the blood oxygen level-dependent (BOLD) signal in
Heschl's gyrus during the patients' hallucinations. Our results provide direct
evidence of the involvement of primary auditory areas in auditory verbal
hallucinations and establish novel constraints for psychopathological models.
PMID- 10197542
TI - Multicultural queer: Australian narratives. Foreword.
PMID- 10197541
TI - Caspase-8 is required for cell death induced by expanded polyglutamine repeats.
AB - We show here that caspase-8 is required for the death of primary rat neurons
induced by an expanded polyglutamine repeat (Q79). Expression of Q79 recruited
and activated caspase-8. Inhibition of caspase-8 blocked polyglutamine-induced
cell death. Coexpression of Q79 with the caspase inhibitor CrmA, a dominant
negative mutant of FADD (FADD DN), Bcl-2, or Bcl-xL, but not an N-terminally
tagged Bcl-xL, prevented the recruitment of caspase-8 and inhibited polyglutamine
induced cell death. Furthermore, Western blot analysis revealed the presence of
activated caspase-8 in the insoluble fraction of affected brain regions from
Huntington's disease (HD) patients but not in those from neurologically
unremarkable controls, suggesting the relocation and activation of caspase-8
during the pathogenesis of HD. These results suggest an essential role of caspase
8 in HD-related neural degenerative diseases.
PMID- 10197543
TI - Introduction: ethnic minorities and the lesbian and gay community.
PMID- 10197544
TI - Using chopsticks to eat steak.
AB - "Rice queens," "small dicks," and "Asian take-aways," are just a few of the
stereotypes that Asian gay men are faced with in Sydney's gay culture. Even
though the author grew up in and quickly assimilated to the general Australian
society, he felt like an outsider when he came out and moved into the gay
community, where race-based sexual perceptions appear to dominate. This article
is a personal exploration of how one Asian gay man came to find a place for
himself within the predominantly white-oriented gay community. For the benefit of
linguistically challenged readers, a glossary of Australian terms is provided at
the end of this very serious article.
PMID- 10197545
TI - "Asian" men on the scene: challenges to "gay communities".
AB - This article examines common assumptions behind the notion of "gay community,"
contrasting these views with the experiences of homosexual men originating from
Southeast Asia on the commercial gay scene in Melbourne, Australia. The
narratives here reveal fragmented social networks involving various social
groups, categories of people and an "In/Out" culture where informants were
culturally marginal. Fitting into the scene culture involves processes of
assimilation, and loss of connection even with supportive ethnic networks. While
all men who look for a place to belong on the scene generally feel pressure to
assimilate to a predominantly white middle-class gay culture, Southeast Asian men
generally had more cultural distance to cover. Men who are not well assimilated
face exclusion, invisibility and discrimination. Differences and discrimination
within Southeast Asian based networks also contributed towards fragmented
relations. This article raises questions about dominant gay cultural forms,
assumptions of gay solidarity, and how ethnic minority men make sense of and
negotiate their sexual and social experiences.
PMID- 10197546
TI - A social psychological perspective on HIV/AIDS and gay or homosexually active
Asian men.
AB - This paper employs findings in social psychological research to analyze HIV/AIDS
related issues among gay and homosexual Asian men living in western countries,
specifically in Australia. This includes analyses of: (1) the impact of
collectivistic cultural ideologies on self-conception and self-esteem; (2) self
identity related to the status of Asians as numerical and status minorities; (3)
the existence of stereotypes of Asians in the gay communities and their
consequences on individual Asians; and (4) issues related to self-esteem of gay
Asian men as determined by their identification with the Asian and/or the gay
communities and acculturation to the dominant Australian Anglo-Celtic culture.
PMID- 10197547
TI - China doll - the experience of being a gay Chinese Australian.
AB - This article is a stylized blend of personal history and polemical essay which
investigates the relationship between race and sexuality. What starts out as a
history of the narrator's experience of being a "banana"-yellow (Chinese) on the
outside and white (Caucasian) on the inside-becomes a complex exploration of the
various ways in which male homosexual desire is constructed and how race is both
included and excluded from western constructions of homosexuality.
PMID- 10197548
TI - The cinematic representation of Asian homosexuality in The Wedding Banquet.
AB - Over the last decade, there has been an increasing number of western films which
represent both homosexuals and Asian people. However, the homosexuals depicted in
these films are often white, and the Asians are almost always heterosexual. In an
attempt to account for the scarcity of western films containing Asian
homosexuals, this paper aims to examine some of the common cinematic tropes and
theoretical discourses used to depict and define both Asians and homosexuals. As
one of the few feature-length films containing an Asian homosexual central
character, Ang Lee's The Wedding Banquet will also be discussed.
PMID- 10197549
TI - Interface: reflections of an ethnic toygirl.
AB - This essay interrogates the colonial modernity of Anglo-Australian lesbian
hegemony through an experimental text which plays with the aesthetics of
cyberspace. Mobilizing the hypertext mark up language (HTML) form of the
Internet, it spatializes the creative, the erotic, and the political that
landscape the vicissitudes of everyday life for a lesbian of Southeast Asian
background living in Australia. "interface" performs as a tryst that drives the
queer body politic through the postcolonial in-formations of color, race, gender
and identity. This text bears indelible marks from multiple sites and sources:
the charges of electronic conversations and etchings on the World Wide Web; the
raw pulp of inner-urban graffiti scrawls; passionate voicemails; racist policies
in queer venues; fury banner posts; luscious lesbian cinema screenings; sexy
fantasy malls; and fleshy style shopping.
PMID- 10197550
TI - Queerer than queer: reflections of a Kike dyke.
AB - In this article the author, a Jewish lesbian academic, reflects on the positive
and negative aspects of her dual identity and explores her feelings of exclusion
from "in groups" in a range of settings. Annie Goldflam carries a legacy of fear
from stories of medieval "witch" burnings and drownings and the twentieth century
Jewish Holocaust, which she reflects on to compare the nature of anti-semitism
and lesbophobia, considering the options of hiding from racist and homophobic
forms of oppression or confronting them. She has chosen to confront, be "out" and
politically active.
PMID- 10197551
TI - Looking out, looking in: anti-semitism and racism in lesbian communities.
AB - I am a white Jewish lesbian from a Non-English Speaking Background (NESB). This
article is based on a speech which I gave at the "Sappho Was A Wog Grrrl"
conference organized by the Interlesbian group in Melbourne in 1995. I discuss
how racism and anti-Semitism are reflected in lesbian communities, examining
issues of privilege, invisibility and exclusion from both personal and community
perspectives. I offer alternatives to ignorance and guilt, suggesting some
strategies for taking responsibility and moving beyond discrimination. This
article is, and remains, a work in progress as I continue to learn and understand
more about anti-Semitism and racism.
PMID- 10197552
TI - A love letter from NADIA (non-anglo dykes in Australia).
AB - This article is a revised version of a paper I presented at the "Sappho Was A Wog
Grrrl" conference in Melbourne, 22 October 1995, which was organized by
"Interlesbian," a Melbourne-based political and support group for lesbians from
Non-English Speaking Backgrounds (NESB). Utilizing a mixed genre format
incorporating the first person fictional narrative form of letters to lovers,
this parodic piece explores the identity terrains of sexuality, ethnicity and
class in Melbourne's lesbian communities. It focuses on how the ethnocentric
limits of sexual, cultural and racial identifications constrain the mythical
beauty of coming out and staying in. The experiences reported and reflected upon
here arose out of my participation as an activist member of Interlesbian.
Contextualized in the form of a lover's discourse, this paper is an evocation of
a passion towards the (re)visioning of a progressive local lesbian activist
politics and community.
PMID- 10197553
TI - Sister outsider, or "just another thing I am": intersections of cultural and
sexual identities in Australia.
AB - This article originates from a radio project titled Muff Divas and Drag Queens
that investigated a wide range of gay and lesbian histories in the state of New
South Wales. The project produced two half-hour radio programs that were
broadcast nationally on community radio stations in February 1996 to coincide
with Sydney's annual month-long Gay and Lesbian Mardi Gras Festival, the premier
event on Australia's queer cultural calendar. Of the two documentaries produced,
the first addressed 30 years of queer culture in New South Wales while the second
explored our diverse identities as lesbians and gay men. This paper draws
extensively on material collected for the second program. Muff Divas and Drag
Queens was funded under the Literature and History Program of the New South Wales
Government's Ministry for the Arts, with support from the Sydney Gay and Lesbian
Mardi Gras cultural program and Sydney community radio station 2SER.FM.
PMID- 10197554
TI - Diary entries from the "teachers' professional development playground":
multiculturalism meets multisexualities in Australian education.
AB - Educational institutions are major cultural and social systems that police and
regulate the living out of multicultural and multisexual queer identities, yet
which also provide sites for anti-discriminatory responses to the marginalization
of these multiple, hybrid identities. Censorship and disapproval (both real and
imagined) together with informal codes and regulations for inclusion and
representation within school and college communities reflect and reproduce formal
debates within the wider society, and within ethnic, feminist, and gay/lesbian
communities. Through a series of "Diary Entries," I document my work and
experiences with educational groups in both secondary and tertiary education in
Australia in recent years-in what a bicultural, bisexual teacher-friend calls
"teachers' professional development playgrounds." I explore dilemmas, concerns
and strategies for placing "multiculturalism" on the "multisexual" agenda and,
conversely, for placing "multisexuality" on the "multicultural" agenda.
PMID- 10197555
TI - Unfixed in a fixated world: identity, sexuality, race and culture.
AB - At the dusk of the twentieth century the confluence of sexuality and the
multicultural subject offers a deep interrogation into identity. On the edge of
the world, Australia is experiencing a poignant moment of identity crisis. For
someone who is from a multicultural, multisexual background, identity is
fragmented. Law and society demand unambiguous subjects, fixed by socio-political
cultural mores and expectations. To be unfixed presents difficulties in
negotiating systems of knowledge and power which are fundamentally homeostatic.
In the end it is all a matter of being unfixed but connected to "others," aware
of the substance beyond identity and labels. This is being unfixed in a fixated
world, challenging gravity, resisting definition and compromise.
PMID- 10197556
TI - Revisiting the effectiveness of the National Cholesterol Education Program's Step
I and Step II diets: cholesterol-lowering diets in a pharmaceutically driven
world.
PMID- 10197557
TI - Energy in pregnancy.
PMID- 10197558
TI - Model for the regulation of energy balance and adiposity by the central nervous
system.
AB - In 1995, we described a new model for adiposity regulation. Since then, data
regarding the biology of body weight regulation has accumulated at a remarkable
rate and has both modified and strengthened our understanding of this homeostatic
system. In this review we integrate new information into a revised model for
further understanding this important regulatory process. Our model of energy
homeostasis proposes that long-term adiposity-related signals such as insulin and
leptin influence the neuronal activity of central effector pathways that serve as
controllers of energy balance.
PMID- 10197559
TI - Genetic effects on weight change and food intake in Swedish adult twins.
AB - BACKGROUND: Obesity is influenced by genetic and environmental factors.
Additionally, synergistic effects of genes and environments may be important in
the development of obesity. OBJECTIVE: The aim of this study was to test for
genetic effects on food consumption frequency, food preferences, and their
interaction with subsequent weight gain. DESIGN: Complete data on the frequencies
of consumption of 11 foods typical of the Swedish diet were available for 98
monozygotic and 176 dizygotic twin pairs aged 25-59 y who are part of the Swedish
Twin Registry. The data were collected in 1973 as part of a questionnaire study.
Body mass index was measured in 1973 and again in 1984. RESULTS: There was some
evidence that genetic effects influenced the frequency of intake of some foods.
Similarity among monozygotic twins exceeded that among dizygotic twins for intake
of flour and grain products and fruit in men and women, intake of milk in men,
and intake of vegetables and rice in women, suggesting that genes influence
preferences for these foods. Analyses conducted for twins reared together and
apart also suggested greater monozygotic than dizygotic correlations, but cross
twin, cross-trait correlations were all insignificant, suggesting that the genes
that affect consumption frequencies are not responsible for mediating the
relation between the frequency of intake and weight change. CONCLUSIONS: Genetic
effects and the frequency of intake are independently related to change in body
mass index. However, there was no suggestion of differential genetic effects on
weight gain that were dependent on the consumption frequency of the foods
studied.
PMID- 10197560
TI - Use of the leg-to-leg bioelectrical impedance method in assessing body
composition change in obese women.
AB - BACKGROUND: There is little information on whether bioelectrical impedance
analysis (BIA) accurately predicts changes in body composition associated with
energy restriction, exercise, or both. OBJECTIVE: We had 2 objectives: to
determine the validity of the leg-to-leg BIA system in 1) estimating body
composition in obese and nonobese women, with a cross-sectional design, and 2)
assessing changes in body composition in obese women in response to 12 wk of
energy restriction, exercise training, or both. DESIGN: Subjects were 98
moderately obese women (43.2 +/- 0.6% body fat, 45.0 +/- 1.1 y of age) and 27
nonobese control subjects (24.0 +/- 1.5% body fat, 43.5 +/- 2.5 y of age). Obese
subjects were randomly divided into 1 of 4 groups, with fat-free mass, fat mass,
and percentage body fat estimated with BIA and underwater weighing before and
after 12 wk of intervention. The 4 groups were diet only (4.19-5.44 MJ/d),
exercise only (five, 45-min sessions/wk at 78.5 +/- 0.5% of maximum heart rate),
both exercise and diet, and control (no diet or exercise). RESULTS: No
significant difference was found between underwater weighing and BIA in
estimating the fat-free mass of the obese and nonobese women (all subjects
combined, r = 0.78, P < 0.001, SEE = 3.7 kg) or in estimating decreases in fat
mass during 12 wk of energy restriction, exercise, or both in obese subjects
(F[3.85] = 1.45, P = 0.233). CONCLUSIONS: The leg-to-leg BIA system accurately
assessed fat-free mass in obese and nonobese women, and changes in fat mass with
diet alone or when combined with exercise.
PMID- 10197561
TI - Like mother, like daughter: familial patterns of overweight are mediated by
mothers' dietary disinhibition.
AB - BACKGROUND: Obese parents are more likely to have obese children. Parents provide
both the genes and eating environment for their children and familial patterns of
adiposity are the result of gene-environment interactions. Environmental factors
are implicated in the rapid increases in prevalence of childhood overweight that
have occurred in the past 2 decades. Examination of aspects of the family
environment may provide insight into increases in childhood overweight over time.
OBJECTIVE: We examined parental characteristics associated with overweight and
eating behaviors in preschool children. DESIGN: Seventy-five preschool children
and their parents were recruited from local daycare centers. Information was
obtained on parents' body mass indexes (BMIs), dietary restraint, and dietary
disinhibition. A behavioral index of disinhibited eating in children was used to
measure children's eating when given free access to palatable snack foods in the
absence of hunger. Children's weight-for-height values were also calculated.
RESULTS: Maternal dietary disinhibition (R2 = 0.35, P < 0.01) and maternal BMI
(R2 = 0.19, P < 0.05) positively predicted daughters' overweight. Maternal
disinhibition (R2 = 0.35, P < 0.05) mediated the relation between mothers' BMI
and daughters' overweight when both maternal disinhibition and maternal BMI were
used to predict daughters' overweight. Furthermore, when both mothers'
disinhibition and daughters' free access intakes were used to predict daughters'
overweight, mothers' disinhibition (P < 0.05) showed independent prediction.
CONCLUSIONS: These findings suggest that familial influences on child overweight
differ according to parent and child sex. Also, these results suggest that
mothers' dietary disinhibition mediates familial similarities in degree of
overweight for mothers and daughters.
PMID- 10197562
TI - An independent, inverse association of high-density-lipoprotein-cholesterol
concentration with nonadipose body mass.
AB - BACKGROUND: Increasing body mass index (BMI) is associated with progressively
lower serum HDL-cholesterol concentrations, although the underlying body
composition compartment accounting for this unfavorable lipid change remains
uncertain. OBJECTIVE: Because growing evidence favors a role of lean tissue in
HDL homeostasis, the hypothesis was tested that non-adipose tissue components of
body mass explain the inverse association of HDL cholesterol and BMI. DESIGN:
Fasting serum lipid concentrations and body composition [total, subcutaneous, and
visceral adipose tissue; adipose tissue-free mass (ATFM); and skeletal muscle by
whole-body magnetic resonance imaging and body cell mass by 40K counting) were
evaluated in healthy adults. Body-composition compartments were expressed as
height2-normalized indexes. RESULTS: An inverse correlation was observed between
serum HDL cholesterol and BMI in women (n = 68; R2 = 0.08, P = 0.023) and men (n
= 61; R2 = 0.07, P = 0.046). Significant inverse correlations (P = 0.005-0.02)
were also observed between HDL cholesterol and nonadipose components (ie, ATFM,
skeletal muscle, and body cell mass) but not between HDL cholesterol and any
adipose tissue component. The association between HDL cholesterol and ATFM
remained significant after serum triacylglycerol was controlled for. When BMI was
entered into the HDL cholesterol-ATFM regression model, BMI was not a significant
independent variable. The strongest correlate of serum triacylglycerol was
visceral adipose tissue (P = 0.002 for both women and men). CONCLUSIONS: Lean
tissues and body cell mass appear to account in part for the long-observed
inverse association of HDL cholesterol and BMI. These observations suggest a link
between nonadipose tissue compartments and the greater cardiovascular risk
associated with high BMI.
PMID- 10197563
TI - Cardiovascular disease risk factors in 2 distinct ethnic groups: Indian and
Pakistani compared with American premenopausal women.
AB - BACKGROUND: Although people from the Indian subcontinent have high rates of
cardiovascular disease (CVD), studies of such in Indian and Pakistani women
living in the United States are lacking. OBJECTIVE: This study accounted for
variability in serum lipid (total cholesterol and triacylglycerol) and
lipoprotein [LDL cholesterol, lipoprotein(a), and HDL cholesterol] concentrations
in Indian and Pakistani compared with American premenopausal women in the United
States. Body composition, regional fat distribution, dietary intake, and energy
expenditure were compared between groups. DESIGN: The 2 groups were 47 Indian and
Pakistani and 47 American women. Health was assessed via medical history,
physical activity, body composition (via anthropometry and dual-energy X-ray
absorptiometry), dietary intake (via 7-d food records), and serum lipids.
RESULTS: Serum total cholesterol, triacylglycerol, LDL cholesterol,
lipoprotein(a), the ratio of total to HDL cholesterol, and the ratio of LDL to
HDL cholesterol were greater (P <0.03), whereas HDL-cholesterol values were lower
(P = 0.011) in Indians and Pakistanis than in Americans. Multiple regression
analysis indicated that approximately 18% of the variance in total cholesterol (P
= 0.0010) and LDL cholesterol (P = 0.0009) was accounted for by ethnicity, energy
expenditure, and the ratio of the sum of central to the sum of peripheral
skinfold thicknesses. Ethnicity, sum of central skinfold thicknesses, ratio of
polyunsaturated to saturated fat, and monounsaturated fat intake accounted for
approximately 43% of the variance in triacylglycerol concentration (P < 0.0001).
Monounsaturated fat, percentage body fat, and alcohol intake accounted for
approximately 26% of variance in HDL cholesterol. Ethnicity contributed
approximately 22% of the 25% overall variance in lipoprotein(a). CONCLUSIONS:
Results suggest that these Indian and Pakistani women are at higher CVD risk than
their American counterparts, but that increasing their physical activity is
likely to decrease overall and regional adiposity, thereby improving their serum
lipid profiles.
PMID- 10197564
TI - Effects of the National Cholesterol Education Program's Step I and Step II
dietary intervention programs on cardiovascular disease risk factors: a meta
analysis.
AB - BACKGROUND: Plasma lipid and lipoprotein responses have been variable in dietary
intervention studies. OBJECTIVE: The objective of this study was to evaluate the
effects of the National Cholesterol Education Program's Step I and Step II
dietary interventions on major cardiovascular disease risk factors using meta
analysis. DESIGN: MEDLINE was used to select 37 dietary intervention studies in
free-living subjects published from 1981 to 1997. RESULTS: Step I and Step II
dietary interventions significantly decreased plasma lipids and lipoproteins.
Plasma total cholesterol (TC), LDL cholesterol, triacylglycerol, and TC:HDL
cholesterol decreased by 0.63 mmol/L (10%), 0.49 mmol/L (12%), 0.17 mmol/L (8%),
and 0.50 (10%), respectively, in Step I intervention studies, and by 0.81 mmol/L
(13%), 0.65 mmol/L (16%), 0.19 mmol/L (8%), and 0.34 (7%), respectively, in Step
II intervention studies (P < 0.01 for all). HDL cholesterol decreased by 7% (P =
0.05) in response to Step II but not to Step I dietary interventions. Positive
correlations between changes in dietary total and saturated fatty acids and
changes in TC and LDL and HDL cholesterol were observed (r = 0.59, 0.61, and
0.46, respectively; P < 0.001). Multiple regression analyses showed that for
every 1% decrease in energy consumed as dietary saturated fatty acid, TC
decreased by 0.056 mmol/L and LDL cholesterol by 0.05 mmol/L. Moreover, for every
1-kg decrease in body weight, triacylglycerol decreased by 0.011 mmol/L and HDL
cholesterol increased by 0.011 mmol/L. Exercise resulted in greater decreases in
TC, LDL cholesterol, and triacylglycerol and prevented the decrease in HDL
cholesterol associated with low-fat diets. CONCLUSION: Step I and Step II dietary
interventions have multiple beneficial effects on important cardiovascular
disease risk factors.
PMID- 10197565
TI - Effect of the glycemic index and content of indigestible carbohydrates of cereal
based breakfast meals on glucose tolerance at lunch in healthy subjects.
AB - BACKGROUND: Diets with a low glycemic index (GI) have been shown to improve
glucose tolerance in both healthy and diabetic subjects. Two potential mechanisms
are discussed in relation to long-term metabolic effects: a decreased demand for
insulin in the postprandial phase and formation of short-chain fatty acids from
fermentation of indigestible carbohydrates in the colon. OBJECTIVE: The objective
was to study the effect of the GI and the indigestible carbohydrate--resistant
starch (RS) and dietary fiber (DF)--content of cereal-based breakfasts on glucose
tolerance at a second meal (lunch) in healthy subjects. DESIGN: The effects of 7
test breakfasts with known GIs (GI: 52-99) and RS + DF contents (2-36 g) were
evaluated. White-wheat bread was used as a reference breakfast (high GI, low RS +
DF content). Glucose and insulin responses after the second meal were measured in
healthy subjects. In addition, the satiating capacity of 4 of the 7 test
breakfasts was estimated before and during the second meal. RESULTS: Two of the 4
low-GI breakfasts improved glucose tolerance at the second meal. Only these 2
breakfasts were capable of postponing the in-between-meal fasting state. There
was no measurable effect of fermentable carbohydrates on glucose tolerance at the
second meal. The highest satiety score was associated with the barley breakfast
that had a low GI and a high RS + DF content. CONCLUSIONS: Glucose tolerance can
improve in a single day. Slow absorption and digestion of starch from the
breakfast meal, but not the content of indigestible carbohydrates in the
breakfast meal, improved glucose tolerance at the second meal (lunch).
PMID- 10197567
TI - Risk of persistent cobalamin deficiency in adolescents fed a macrobiotic diet in
early life.
AB - BACKGROUND: Cobalamin deficiency has been described in children consuming
macrobiotic diets. OBJECTIVE: We investigated whether moderate consumption of
animal products is sufficient for achieving normal cobalamin function in 73
adolescents who had received a macrobiotic diet until 6 y of age and had then
switched to a lactovegetarian, lactoovovegetarian, or omnivorous diet
(macrobiotic adolescents). DESIGN: Hematologic indexes and serum concentrations
of methylmalonic acid (MMA), total homocysteine (tHcy), and folate were measured.
Current consumption frequency of animal products and cobalamin intake from dairy
products were assessed by questionnaire. Data from 94 age-matched adolescents who
received an omnivorous diet from birth were used as a reference. RESULTS: Serum
cobalamin concentrations were significantly lower and concentrations of MMA and
folate and mean corpuscular volume (MCV) were significantly higher in macrobiotic
adolescents than in control adolescents: of macrobiotic adolescents, 21% had
abnormal MMA concentrations (>0.41 micromol/L), 37% had abnormal cobalamin
concentrations (<218 pmol/L), 10% had abnormal tHcy concentrations (> 12.8
micromol/L), and 15% had abnormal MCV (> 89 fL). In macrobiotic adolescents,
dairy products (200 g milk or yogurt and 22 g cheese/d) supplied on average 0.95
microg cobalamin/d; additionally, these adolescents consumed fish, meat, or
chicken 2-3 times/wk. In girls, meat consumption contributed more to cobalamin
status than the consumption of dairy products, whereas in boys these food groups
were equally important. CONCLUSIONS: A substantial number of the formerly strict
macrobiotic adolescents still had impaired cobalamin function. Thus, moderate
consumption of animal products is not sufficient for restoring normal cobalamin
status in subjects with inadequate cobalamin intake during the early years of
life.
PMID- 10197566
TI - Safety of <7500 RE (<25000 IU) vitamin A daily in adults with retinitis
pigmentosa.
AB - BACKGROUND: Vitamin A supplementation is being used successfully to treat some
forms of cancer and the degenerative eye disease retinitis pigmentosa. The daily
biological need for vitamin A is estimated to be 800 retinol equivalents (RE)/d
(2667 IU/d) for adult women and 1000 RE/d (3300 IU/d) for adult men; doses > or =
7500 RE (> or = 25000 IU)/d are considered potentially toxic over the long term.
OBJECTIVE: We assessed the safety in adults of long-term vitamin A
supplementation with doses above the daily biological need but <7500 RE (<25000
IU)/d. DESIGN: Adults aged 18-54 y with retinitis pigmentosa but in generally
good health (n = 146) were supplemented with 4500 RE (15000 IU) vitamin A/d for <
or = 12 y (group A) and compared with a similar group (n = 149) that received 23
RE (75 IU)/d (trace group). Mean total consumption of vitamin A in group A was
5583 RE (18609 IU)/d (range: 4911-7296 RE/d, or 16369-24318 IU/d) and that in the
trace group was 1053 RE (3511 IU)/d (range: 401-3192 RE/d, or 1338-10638 IU/d).
RESULTS: Patients in group A showed an 8% increase in mean serum retinol
concentration at 5 y and an 18% increase at 12 y (P < 0.001); no retinol value
exceeded the upper normal limit (3.49 micromol/L, or 100 microg/dL). Mean serum
retinyl esters were elevated approximately 1.7-fold at 5 y and remained
relatively stable thereafter. No clinical symptoms or signs of liver toxicity
attributable to vitamin A excess were detected. CONCLUSIONS: Prolonged daily
consumption of <7500 RE (<25000 IU) vitamin A/d can be considered safe in this
age group.
PMID- 10197568
TI - Riboflavin and riboflavin-derived cofactors in adolescent girls with anorexia
nervosa.
AB - BACKGROUND: Thyroid hormones, riboflavin, riboflavin cofactors, and organic acids
were assessed in girls with anorexia nervosa. OBJECTIVE: The objective was to
examine the effect of malnutrition and low thyroid hormone concentrations on
erythrocyte and plasma riboflavin metabolism and their relation with urinary
organic acid excretion. DESIGN: Seventeen adolescent girls with anorexia nervosa
[body mass index (BMI; in kg/m2): 14.8 +/- 2.2] and 17 age-matched, healthy girls
(control subjects; BMI: 20.5 +/- 2.2) took part in the feeding study. Erythrocyte
and plasma riboflavin as well as riboflavin cofactors (flavin mononucleotide and
flavin adenine dinucleotide) were assessed by HPLC, whereas urinary organic acids
were assessed by gas chromatography-mass spectrometry. RESULTS: Anorectic
patients who began a feeding program had higher erythrocyte riboflavin (3.5 +/-
2.2 compared with <0.1 nmol/mol hemoglobin; P < 0.001), lower plasma flavin
adenine dinucleotide (57.8 +/- 18.5 compared with 78.5 +/- 54.3 nmol/L; P <
0.05), and higher urinary ethylmalonic acid (7.12 +/- 4.39 compared with 1.3 +/-
2.8 micromol/mmol creatinine; P < 0.001) and isovalerylglycine (7.65 +/- 4.78
compared with 3.8 +/- 0.9 micromol/mmol creatinine; P < 0.05) concentrations than
did control subjects. Triiodothyronine concentrations were low and negatively
correlated with plasma riboflavin concentrations (r = -0.69, P < 0.01). Not all
patients showed improvements in these biochemical indexes after 30 d of
refeeding. CONCLUSIONS: The low triiodothyronine concentrations observed in
anorexia nervosa could alter the extent of riboflavin conversion into cofactors,
thus leading to high erythrocyte riboflavin concentrations, low plasma flavin
adenine dinucleotide concentrations, and high rates of ethylmalonic acid and
isovalerylglycine excretion.
PMID- 10197569
TI - Age of introduction of complementary foods and growth of term, low-birth-weight,
breast-fed infants: a randomized intervention study in Honduras.
AB - BACKGROUND: The optimal age at which to introduce complementary foods is a topic
of considerable debate. OBJECTIVE: This study was designed to evaluate this issue
in a nutritionally vulnerable population in Honduras. DESIGN: Mothers of low
birth-weight (1500-2500 g) term (ie, small-for-gestational-age) infants were
recruited in the hospital and assisted with exclusive breast-feeding during the
first 4 mo. At 4 mo, mothers were randomly assigned to either continue exclusive
breast-feeding to 6 mo (EBF; n = 59) or to feed complementary solid foods (jarred
rice cereal, chicken, and fruit and vegetables) twice daily from 4 to 6 mo while
continuing to breast-feed at their initial frequency (SF; n = 60). At 4 and 6 mo,
breast milk and total energy intake were measured for a nonrandom subsample
(those who could stay overnight in a central unit: 32 EBF and 31 SF). RESULTS: At
4 mo, breast milk intake in the subsample was not significantly different between
groups (EBF: 729 +/- 135 g/d; SF: 683 +/- 151 g/d: P >0.2); from 4 to 6 mo it
increased (by 28 g/d) in the EBF group but decreased (by 39 g/d) in the SF group
(P < 0.005). Nonetheless, total energy intake (including solid foods) increased
more from 4 to 6 mo in the SF than in the EBF group. However, there were no
significant differences between groups in weight or length gain during the
intervention or subsequently (6-12 mo). CONCLUSION: There was no growth advantage
of complementary feeding of small-for-gestational-age, breast-fed infants between
4 and 6 mo of age.
PMID- 10197570
TI - Effects of dietary mixtures of amino acids on fetal growth and maternal and fetal
amino acid pools in experimental maternal phenylketonuria.
AB - BACKGROUND: Branched-chain amino acids have been reported to improve fetal brain
development in a rat model in which maternal phenylketonuria (PKU) is induced by
the inclusion of an inhibitor of phenylalanine hydroxylase, DL-p
chlorophenylalanine, and L-phenylalanine in the diet. OBJECTIVE: We studied
whether a dietary mixture of several large neutral amino acids (LNAAs) would
improve fetal brain growth and normalize the fetal brain amino acid profile in a
rat model of maternal PKU induced by DL-alpha-methylphenylalanine (AMPhe).
DESIGN: Long-Evans rats were fed a basal diet or a similar diet containing 0.5%
AMPhe + 3.0% L-phenylalanine (AMPhe + Phe diet) from day 11 until day 20 of
gestation in experiments to test various mixtures of LNAAs. Maternal weight gains
and food intakes to day 20, fetal body and brain weights at day 20, and fetal
brain and fetal and maternal plasma amino acid concentrations at day 20 were
measured. RESULTS: Concentrations of phenylalanine and tyrosine in fetal brain
and in maternal and fetal plasma were higher and fetal brain weights were lower
in rats fed the AMPhe + Phe diet than in rats fed the basal diet. However, fetal
brain growth was higher and concentrations of phenylalanine and tyrosine in fetal
brain and in maternal and fetal plasma were lower in rats fed the AMPhe + Phe
diet plus LNAAs than in rats fed the diet containing AMPhe + Phe alone.
CONCLUSION: LNAA supplementation of the diet improved fetal amino acid profiles
and alleviated most, but not all, of the depression in fetal brain growth
observed in this model of maternal PKU.
PMID- 10197571
TI - Longitudinal assessment of energy balance in well-nourished, pregnant women.
AB - BACKGROUND: Clinicians often recommend an additional energy intake of 1250 kJ/d
to their pregnant patients. Previous studies have shown considerable variation in
the metabolic response to pregnancy and thus in the additional energy required to
support a pregnancy. OBJECTIVE: The purpose of this study was to assess how well
nourished women meet the energy demands of pregnancy and to identify factors that
predict an individual's metabolic response. DESIGN: Resting metabolic rate (RMR),
diet-induced thermogenesis (DIT), total energy expenditure (TEE), activity energy
expenditure (AEE), energy intake (EI), and body fat mass (FM) were measured
longitudinally in 10 women preconception; at 8-10, 24-26, and 34-36 wk of
gestation; and 4-6 wk postpartum. RESULTS: Compared with preconception values,
individual RMRs increased from 456 to 3389 kJ/d by late pregnancy. DIT varied
from -266 to 110 kJ/meal, TEE from -105 to 3421 kJ/d, AEE from -2301 to 2929
kJ/d, EI from -259 to 2176 kJ/d, and FM from a 0.6-kg loss to a 10.6-kg gain. The
only prepregnant factor that predicted FM gain was RMR (r = 0.65, P < 0.05).
Women with the largest cumulative increase in RMR deposited the least FM (r =
0.64, P < 0.05). CONCLUSIONS: Well-nourished women use different strategies to
meet the energy demands of pregnancy, including reductions in DIT or AEE,
increases in EI, and deposition of less FM than anticipated. The combination of
strategies used by individual women is not wholly predictable from prepregnant
indexes. The use of a single recommendation for increased energy intake in all
pregnant women is not justified.
PMID- 10197572
TI - Correlates of individual differences in body-composition changes resulting from
physical training in obese children.
AB - BACKGROUND: No studies have been reported in children that assess correlates of
body-composition changes in response to a physical training intervention.
OBJECTIVE: The hypothesis studied was that variation in diet and physical
activity would explain a significant portion of the interindividual variation in
the response of body composition to physical training. DESIGN: The participants
were 71 obese children aged 7-11 y (22 boys, 49 girls; 31 whites, 40 blacks).
Body composition was measured by dual-energy X-ray absorptiometry, physical
activity by a 7-d recall interview, and diet by two, 2-d recalls. The children
underwent 4 mo of physical training. RESULTS: The mean attendance was 4 d/wk, the
mean (+/-SD) heart rate for the 40-min sessions was 157 +/- 7 beats/min, and the
mean energy expenditure was 946 +/- 201 kJ/session. On average, the percentage
body fat decreased significantly in the total group, and total mass, fat-free
soft tissue, bone mineral content, and bone mineral density increased, but there
was a good deal of individual variability. Multiple regression models indicated
that in general, more frequent attendance, being a boy, lower energy intake, and
more vigorous activity were associated with healthier body-composition changes
with physical training. Ethnicity was not retained as a correlate of the change
of any component of body composition. CONCLUSIONS: In obese children, age,
vigorous activity, diet, and baseline percentage body fat together accounted for
25% of the variance in the change in percentage body fat with physical training.
PMID- 10197573
TI - Does tomato consumption effectively increase the resistance of lymphocyte DNA to
oxidative damage?
AB - BACKGROUND: Lycopene, the main carotenoid in tomato, has been shown to be a
potent antioxidant in vitro. However, there is no significant evidence of its
antioxidant action in vivo. OBJECTIVE: We evaluated the effect of tomato intake
on plasma carotenoid concentrations and lymphocyte resistance to oxidative
stress. DESIGN: Ten healthy women (divided into 2 groups of 5 subjects each) ate
a diet containing tomato puree (providing 16.5 mg lycopene) and a tomato-free
diet for 21 d each in a crossover design. Before and after each diet period,
plasma carotenoid concentrations and primary lymphocyte resistance to oxidative
stress (evaluated by means of single-cell gel electrophoresis) were analyzed.
RESULTS: After the first 21-d experimental period, total plasma lycopene
concentrations increased by 0.5 micromol/L (95% CI: 0.14, 0.87) in the group that
consumed the tomato diet and decreased by 0.2 micromol/L (95% CI: -0.11, -0.30)
in the group that consumed the tomato-free diet (P < 0.001). Tomato consumption
also had an effect on cellular antioxidant capacity: lymphocyte DNA damage after
ex vivo treatment with hydrogen peroxide decreased by 33% (95% CI: 0.8%, 61%; P <
0.05) and by 42% (95% CI: 5.1%, 78%; P < 0.05) in the 2 groups of subjects after
consumption of the tomato diet. CONCLUSION: The consumption of tomato products
may reduce the susceptibility of lymphocyte DNA to oxidative damage.
PMID- 10197574
TI - Socioeconomic differences in weight gain and determinants and consequences of
coronary risk factors.
AB - BACKGROUND: The increasing prevalence of overweight and obesity is a major public
health concern in many developed countries. OBJECTIVE: We aimed to describe
socioeconomic differences in change in body mass index (BMI; in kg/m2) from age
25 y, assess possible factors behind these differences, and study whether
socioeconomic differences in a variety of coronary risk factors can be accounted
for by change in BMI. DESIGN: The data come from a cohort study of London-based
civil servants (Whitehall II), who participated in the first (1985-1988) and
third (1991-1993) phases of the study and were 35-55-y old at phase 1: altogether
there were 5507 men and 2466 women. Both study phases included a questionnaire
and a screening examination. RESULTS: In men and women, employment grade--the
measure of socioeconomic status used in this cohort--was strongly related to BMI
gain from age 25 y to phase 3 (25 y apart on average). The lower the grade the
larger the gain in BMI. Adjustment for health behaviors reduced the grade
differences in BMI gain by approximately 20%. A substantial part of the grade
differences in diastolic and systolic blood pressure and plasma triacylglycerol
concentrations could be accounted for by BMI change from age 25 y. CONCLUSIONS:
Grade differences in BMI change are evident, but many of the determinants of
these differences remain unknown. If lower-status persons continue to gain weight
more rapidly than higher-status persons, overweight is likely to be of growing
importance as a pathway to social inequalities in ill health.
PMID- 10197575
TI - Potassium, magnesium, and fruit and vegetable intakes are associated with greater
bone mineral density in elderly men and women.
AB - BACKGROUND: Osteoporosis and related fractures will be growing public health
problems as the population ages. It is therefore of great importance to identify
modifiable risk factors. OBJECTIVE: We investigated associations between dietary
components contributing to an alkaline environment (dietary potassium, magnesium,
and fruit and vegetables) and bone mineral density (BMD) in elderly subjects.
DESIGN: Dietary intake measures were associated with both cross-sectional
(baseline) and 4-y longitudinal change in BMD among surviving members of the
original cohort of the Framingham Heart Study. Dietary and supplement intakes
were assessed by food-frequency questionnaire, and BMD was measured at 3 hip
sites and 1 forearm site. RESULTS: Greater potassium intake was significantly
associated with greater BMD at all 4 sites for men and at 3 sites for women (P <
0.05). Magnesium intake was associated with greater BMD at one hip site for both
men and women and in the forearm for men. Fruit and vegetable intake was
associated with BMD at 3 sites for men and 2 for women. Greater intakes of
potassium and magnesium were also each associated with less decline in BMD at 2
hip sites, and greater fruit and vegetable intake was associated with less
decline at 1 hip site, in men. There were no significant associations between
baseline diet and subsequent bone loss in women. CONCLUSION: These results
support the hypothesis that alkaline-producing dietary components, specifically,
potassium, magnesium, and fruit and vegetables, contribute to maintenance of BMD.
PMID- 10197576
TI - Bioavailability of iron glycine.
PMID- 10197577
TI - Mild cobalamin deficiency in older Dutch subjects.
PMID- 10197578
TI - Use of daily compared with weekly iron supplementation: apples and pears.
PMID- 10197579
TI - No evidence for dietary protein and dietary salt as main factors of calcium
excretion in healthy children and adolescents.
PMID- 10197580
TI - Radiation biology and treatment options in radiation oncology.
PMID- 10197581
TI - Insights from Bcl-2 and Myc: malignancy involves abrogation of apoptosis as well
as sustained proliferation.
AB - The chromosome translocations typifying Burkitt's lymphoma and follicular
lymphoma deregulate very different oncogenes, myc and bcl-2. Transgenic mouse
models have illuminated how each contributes to lymphomagenesis. Constitutive myc
expression provokes sustained cell proliferation and retards differentiation.
However, the resulting expansion in cell number is self-limiting, because the
cells remain dependent on cytokines and undergo apoptosis when these become
limiting. In contrast, bcl-2 is the prototype of a new class of oncogene that
enhances cell survival but does not promote proliferation. Coexpression of these
genes leads to the rapid transformation of lymphocytes, probably because each can
counter an antioncogenic aspect of the other. Several close homologues of Bcl-2
also enhance cell survival and are thus potential oncogenes; each is essential
for maintenance of particular major organs. More distant Bcl-2 relatives instead
promote apoptosis and can be regarded as tumor suppressors. For many but not all
apoptic signals, the balance between these competing activities determines cell
survival. Learning how to adjust the apoptotic threshold in cancer cells should
promote development of more effective therapeutic strategies.
PMID- 10197582
TI - BCL-2 gene family and the regulation of programmed cell death.
AB - The BCL-2 gene was identified at the chromosomal breakpoint of t(14; 18)-bearing
human follicular B cell lymphomas. BCL-2 proved to block programmed cell death
rather than promote proliferation. Transgenic mice that overexpress Bcl-2 in the
B cell lineage demonstrate extended cell survival and progress to high-grade
lymphomas. Thus, BCL-2 initiated a new category of oncogenes, regulators of cell
death. Bcl-2-deficient mice demonstrate fulminant apoptosis of lymphocytes,
profound renal cell death and loss of melanocytes. BCL-2 protein duels with its
counteracting twin, a partner known as BAX. When BAX is in excess, cells execute
a death command; but, when BCL-2 dominates, the program is inhibited and cells
survive. Bax-deficient mice display cellular hyperplasia, confirming its role as
a proapoptotic molecule. An expanded family of BCL-2-related proteins shares
homology clustered within four conserved regions termed BCL-2 homology 1 through
4 (BH1-4). These novel domains control the ability of these proteins to dimerize
and function. An amphipathic alpha helix, BH3, is of particular importance for
the proapoptotic family members. BID and BAD represent an evolving set of
proapoptotic molecules, which bear sequence homology only at BH3. They appear to
reside more proximal in the pathway serving as death ligands. BAD connects
upstream signal transduction paths with the BCL-2 family, modulating this
checkpoint for apoptosis. In the presence of survival factor interleukin-3, cells
phosphorylate BAD on two serine residues. This inactivated BAD is held by the 14
3-3 protein, freeing BCL-XL and BCL-2 to promote survival. Activation of BAX
results in the initiation of apoptosis. Downstream events in this program include
mitochondrial dysfunction, as well as Caspase activation. The pro- and
antiapoptotic BCL-2 family members represent central regulators in an
evolutionarily conserved pathway of cell death. Aberrations in the BCL-2 family
result in disordered homeostasis, a pathogenic event in diseases, including
cancer.
PMID- 10197583
TI - Genetic control of programmed cell death in the nematode Caenorhabditis elegans.
AB - Studies of the development of the nematode Caenorhabditis elegans established
that programmed cell death involves specific genes and proteins and that those
genes and proteins act within the cells that die. This finding revealed that cell
death is a fundamental and active biological process, much like cell division and
cell differentiation. The characterization of genes responsible for programmed
cell death in C. elegans has defined a molecular genetic pathway. This pathway is
conserved evolutionarily and provides a basis for understanding programmed cell
death in more complex organisms, including humans. Knowledge of the mechanisms of
programmed cell death should help lead to new methods for the diagnosis and
treatment of human diseases characterized by too many or too few cell deaths,
including cancer.
PMID- 10197584
TI - Pax genes and their role in organogenesis.
AB - Pax genes have been cloned on the basis of their homology to the Drosophila
segmentation gene paired. They share a common domain, the paired domain, that is
sufficient to mediate sequence-specific DNA binding. Thus far, nine members have
been characterized, which exhibit highly restricted temporal and spatial
expression patterns. The analysis of mouse mutants has revealed their crucial
role in the formation of a variety of tissues. In particular, they are involved
in the regulation of early steps in organ development. They act to define the
regional specification of distinct germ layers.
PMID- 10197585
TI - The role of chimeric paired box transcription factors in the pathogenesis of
pediatric rhabdomysarcoma.
AB - Alveolar rhabdomyosarcoma (ARMS) is an aggressive pediatric soft tissue tumor
with striated muscle differentiation. Chromosomal studies of these tumors
identified 2;13 and 1;13 translocations. Using physical mapping and cloning
strategies, we determined that t(2;13) and t(1;13) rearrange PAX3 and PAX7, which
encode members of the paired box transcription factor family, and juxtapose these
genes with FKHR, which encodes a novel member of the fork head transcription
factor family. These translocations result in chimeric transcripts consisting of
5' PAX3 or PAX7 exons fused to 3' FKHR exons, which encode fusion proteins
containing the PAX3 or PAX7 DNA-binding domain and the COOH-terminal FKHR
transcriptional activation domain. In transfection studies, the PAX3-FKHR fusion
activates transcription of reporter genes containing PAX DNA-binding sites, and
is 10-100-fold more potent as a transcriptional activator than is wild-type PAX3.
This increased function results from the insensitivity of the COOH-terminal FKHR
activation domain to the inhibitory effects of NH2-terminal PAX3 domains. In
addition to functional alterations, our studies demonstrated PAX3-FKHR and PAX7
FKHR overexpression resulting from two distinct mechanisms, increased
transcription of PAX3-FKHR by a copy number-independent mechanism, and gene
amplification of PAX7-FKHR. These findings indicate that the genetic changes in
these tumors result in high levels of chimeric transcription factors that are
hypothesized to inappropriately activate transcription of genes with PAX DNA
binding sites and thereby induce tumorigenic behavior. The differences in
overexpression strategies suggest important differences between the mechanisms
for regulating PAX3 and PAX7 expression. These differences extend to the
phenotypic level, at which clinical differences have been found between the two
ARMS subtypes: PAX7-FKHR tumors more often occur as localized lesions in the
extremities of younger patients and are associated with longer event-free
survival as compared to PAX3-FKHR tumors. Therefore, the clinical heterogeneity
within the ARMS category is associated with genetic heterogeneity. Further
analysis of the transcriptional function, regulation of expression, and
phenotypic effects will help to elucidate the action of these fusion products and
the biological basis of the clinical heterogeneity.
PMID- 10197586
TI - The partial homeodomain of the transcription factor Pax-5 (BSAP) is an
interaction motif for the retinoblastoma and TATA-binding proteins.
AB - Pax-5 codes for the transcription factor BSAP, which plays an important role in
midbrain patterning, B cell development, and lymphoma formation. Pax-5 is known
to control gene expression by recognizing its target genes via the NH2-terminal
paired domain and by regulating transcription through a COOH-terminal regulatory
module consisting of activating and inhibitory sequences. The central region of
Pax-5 contains a sequence with significant homology to the first alpha-helix of
the paired-type homeodomain. This partial homeodomain has been highly conserved
throughout vertebrate evolution because it is found not only in Pax-5 but also in
the related Pax-2 and Pax-8 members of the same Pax subfamily. Here we report
that the partial homeodomain binds the TATA-binding protein (TBP) and
retinoblastoma (Rb) gene product. Both TBP and Rb were shown by
coimmunoprecipitation experiments to directly associate with Pax-5 in vivo. The
conserved core domain of TBP and the pocket region as well as COOH-terminal
sequences of Rb are required for interaction with the partial homeodomain of Pax
5 in in vitro binding assays. Furthermore, Pax-5 was specifically bound only by
the underphosphorylated form of Rb. These data indicate that Pax-5 is able to
contact the basal transcription machinery through the TBP-containing initiation
factor TFIID, and that its activity can be controlled by the cell cycle-regulated
association with Rb.
PMID- 10197587
TI - Id gene expression as a key mediator of tumor cell biology.
AB - Id genes encode members of the helix-loop-helix (HLH) family of transcription
factors that inhibit transcription by forming inactive heterodimers with basic
HLH (bHLH) proteins. There are four members of the Id gene family recognized in
mammals, and the proteins they encode share homology primarily in their HLH
domain. bHLH proteins typically form heterodimers with other bHLH proteins, and
their basic domain binds to a DNA sequence element, the E-box, activating
transcription. Products of Id genes lack the basic DNA binding domain of the bHLH
transcription factors, and when they heterodimerize with bHLH proteins, the
complexes are inactive. Generally, high levels of Id mRNA are detected in
proliferative undifferentiated, embryonal cells and lower levels are detected in
well-differentiated, mature, adult tissues. In vitro, these genes are generally
expressed at lower levels in cells after the induction of differentiation.
Recently, high levels of expression of Id genes have been identified in cell
lines derived from a wide variety of different tumors and in tumor tissues as
well. These findings suggest that not only the inappropriate proliferation of
tumors but also the anaplastic characteristics that contribute to their malignant
behavior may be regulated by Id gene expression.
PMID- 10197588
TI - Developmental basis of retinal-specific induction of cancer by RB mutation.
AB - Understanding why children with RB mutations specifically develop retinoblastoma
will contribute to the understanding of the fundamental principles of cancer.
Only a subset of developing retinal cells are at risk for developing cancer when
RB is mutant because rod photoreceptor and bipolar cells never normally express
RB. Retinoblastomas are observed to arise commonly in the inner nuclear layer,
where they can show features attributed to outer nuclear layer cells
(photoreceptors). The best-studied function of RB is control of the cell cycle,
and the usual tissue consequence of loss of RB is apoptosis. Perhaps the
specificity of RB mutation for retinal cancer resides in the dependency of this
tissue on programmed cell death to achieve a precise architecture of individual
types of interconnecting neurons. The additional mutations that are present in
all retinoblastoma, such as the i(6p) marker chromosome, may interrupt signals
that normally would induce apoptosis when RB is absent. A combination of loss of
cell cycle control and loss of signals that delete extra cells would result in
retinoblastoma.
PMID- 10197589
TI - The phenotypes associated with ret mutations in the multiple endocrine neoplasia
type 2 syndrome.
AB - Different specific mutations in the ret tyrosine kinase give rise to different
clinical types of the inherited cancer syndrome multiple endocrine neoplasia type
2 (MEN 2). The explanation for these genotype-phenotype correlations is not yet
certain. Several lines of evidence suggest that they result either from different
levels of RET activation induced by different mutations or, in one class of
mutation, possibly from altered substrate specificity of the RET tyrosine kinase.
ret is expressed during development in a lineage of neuroectodermal cells that
gives rise to the thyroid C cells and the adrenal medulla, which are involved in
tumor formation in MEN 2. ret is also expressed in the enteric autonomic nervous
system. Inactivating mutations of ret lead to Hirschsprung's disease, a
congenital absence or maldevelopment of the enteric plexuses, whereas activating
mutations in one variety of the MEN 2 syndrome lead to their overgrowth. The
range of phenotypic expression seen in families with different ret mutations and
the variation within families with the same mutation provide a potentially
interesting and tractable system for the analysis of both the relationship
between phenotype and genotype and the effects of modifier genes.
PMID- 10197590
TI - Imprinting of a genomic domain of 11p15 and loss of imprinting in cancer: an
introduction.
AB - Our laboratory has found genomic imprinting of a large genomic domain of human
11p15.5, identifying six imprinted genes within this domain: (a) insulin-like
growth factor II (IGF-II), an important autocrine growth factor in a wide variety
of malignancies; (b) H19, an untranslated RNA that is a putative growth
suppressor gene regulating IGF-II; (c) p57KIP2, a cyclin-dependent kinase
inhibitor that causes G1-S arrest; (d) KvLQT1, a voltage-gated potassium channel;
(e) TSSC3, a gene that is homologous to mouse TDAG51, which is implicated in Fas
mediated apoptosis; and (f) TSSC5, a putative transmembrane protein-encoding
gene. We hypothesize that 11p15 harbors a large domain of imprinted growth
regulatory genes that are important in cancer. Several lines of evidence support
this hypothesis: (a) we have discovered a novel genetic alteration in cancer,
loss of imprinting, which affects several of these genes, and is one of the most
common genetic changes in human cancer; (b) we have found that the hereditary
disorder Beckwith-Wiedemann syndrome, which predisposes to cancer and causes
prenatal overgrowth, involves alterations in p57KIP2, IGF-II, H19, and KvLQT1;
(c) we have found both genetic (somatic mutation in Wilms' tumor) and epigenetic
alterations (DNA methylation) in cancer; and (d) we can partially reverse
abnormal imprinting using an inhibitor of DNA methylation. We propose a model of
genomic imprinting as a dynamic developmental process involving a chromosomal
domain. According to this model, cancer involves both genetic and epigenetic
mechanisms affecting this imprinted domain and the genes within it.
PMID- 10197591
TI - Multiple roles for the Wilms' tumor suppressor, WT1.
AB - Wilms' tumor is a childhood kidney tumor that is a striking example of the way
that cancer may arise through development gone awry. A proportion of these tumors
develop as a result of the loss of function mutations in the Wilms' tumor
suppressor gene, WT1. Inherited mutations in the WT1 gene can lead to childhood
kidney cancer, severe gonadal dysplasia, and life-threatening hypertension.
Knockouts show that the gene is essential for the early stages of kidney and
gonad formation. These tissues are completely absent in null mice. The WT1 gene
encodes numerous protein isoforms, all of which share four zinc fingers. There is
a large body of evidence supporting the notion that WT1 is a transcription
factor, particularly a transcriptional repressor. Recently, however, we obtained
evidence that WT1 colocalizes and is physically associated with splice factors.
What is more, one alternative splice isoform of WT1 containing three amino acids,
Lys-Thr-Ser (KTS; inserted between zinc fingers 3 and 4) is preferentially
associated with splice factors, whereas the other alternative splice version,
lacking these three amino acids, preferentially associates with the
transcriptional apparatus. Both genetic and evolutionary considerations suggest
that these two different forms of the protein have different functions. We will
discuss recent evidence to further implicate WT1 in splicing. Our results raise
the possibility that regulation of splicing is a crucial factor in the
development of the genitourinary system, and that tumors may arise through
aberrant splicing. To pursue the regulation and function of WT1 in whole animals,
we have been introducing the human gene and large flanking regions cloned in
yeast artificial chromosomes directly into mice. These studies have allowed us to
dissect the function of WT1 at late as well as at early stages in organogenesis
and to identify new sites and surprising new potential functions for the gene.
PMID- 10197592
TI - BRCA1, BRCA2, and Rad51 operate in a common DNA damage response pathway.
AB - The two major hereditary breast cancer susceptibility genes, BRCA1 and BRCA2, are
associated with early-onset breast and/or ovarian cancer and encode products that
each interact with the product of the eukaryotic RecA homologue, hRad51. We have
recently found that BRCA1 and BRCA2 coexist in a common biochemical complex. The
two proteins also colocalize in subnuclear foci in somatic cells as well as on
the axial elements of developing synaptonemal complexes in meiotic cells. Thus,
BRCA1 and BRCA2 participate in a common DNA damage response pathway associated
with the activation of homologous recombination and double-strand break repair.
Dysfunction of this pathway may be a general phenomenon in the majority of cases
of hereditary breast and/or ovarian cancer. The BRCA1/BRCA2 complex may function
in postreplicational repair processes activated during the DNA synthesis stage of
the cell cycle.
PMID- 10197593
TI - Tissue structure, nuclear organization, and gene expression in normal and
malignant breast.
AB - Because every cell within the body has the same genetic information, a
significant problem in biology is to understand how cells within a tissue express
genes selectively. A sophisticated network of physical and biochemical signals
converge in a highly orchestrated manner to bring about the exquisite regulation
that governs gene expression in diverse tissues. Thus, the ultimate decision of a
cell to proliferate, express tissue-specific genes, or apoptose must be a
coordinated response to its adhesive, growth factor, and hormonal milieu. The
unifying hypothesis examined in this overview is that the unit of function in
higher organisms is neither the genome nor the cell alone but the complex, three
dimensional tissue. This is because there are bidirectional connections between
the components of the cellular microenvironment (growth factors, hormones, and
extracellular matrix) and the nucleus. These connections are made via membrane
bound receptors and transmitted to the nucleus, where the signals result in
modifications to the nuclear matrix and chromatin structure and lead to selective
gene expression. Thus, cells need to be studied "in context", i.e., within a
proper tissue structure, if one is to understand the bidirectional pathways that
connect the cellular microenvironment and the genome. In the last decades, we
have used well-characterized human and mouse mammary cell lines in "designer
microenvironments" to create an appropriate context to study tissue-specific gene
expression. The use of a three-dimensional culture assay, developed with
reconstituted basement membrane, has allowed us to distinguish normal and
malignant human breast cells easily and rapidly. Whereas normal cells become
growth arrested and form organized "acini," tumor cells continue to grow, pile
up, and in general fail to respond to extracellular matrix and microenvironmental
cues. By correcting the extracellular matrix-receptor (integrin) signaling and
balance, we have been able to revert the malignant phenotype when a human breast
tumor cell is cultured in, or on, a basement membrane. Most recently, we have
shown that whereas beta1 integrin and epidermal growth factor receptor signal
transduction pathways are integrated reciprocally in three-dimensional cultures,
on tissue culture plastic (two-dimensional monolayers), these are not
coordinated. Finally, we have demonstrated that, rather than passively reflecting
changes in gene expression, nuclear organization itself can modulate cellular and
tissue phenotype. We conclude that the structure of the tissue is dominant over
the genome, and that we may need a new paradigm for how epithelial-specific genes
are regulated in vivo. We also argue that unless the structure of the tissue is
critically altered, malignancy will not progress, even in the presence of
multiple chromosomal mutations.
PMID- 10197594
TI - Mammary gland development, reproductive history, and breast cancer risk.
AB - The observation that normal pathways of differentiation and development are
invariably altered during the process of carcinogenesis implies an intrinsic
relationship between these processes. This relationship is particularly evident
in the breast, as exemplified by the existence of endocrine risk factors for
breast cancer that are related to the timing of normal developmental events.
Understanding the mechanisms by which normal developmental events alter breast
cancer risk is a central focus of our laboratory. Herein, we describe three
approaches being taken in our laboratory toward defining the molecular basis of
this relationship. These include: determining the roles played by the tumor
suppressor genes, BRCA1 and BRCA2, in the normal differentiation and development
of the breast; studying the function of three novel protein kinases identified in
our laboratory in mammary epithelial development; and defining the molecular and
cellular changes that occur in the breast as a result of reproductive events
known to influence breast cancer risk.
PMID- 10197595
TI - Identification and characterization of collaborating oncogenes in compound mutant
mice.
AB - We have used proviral tagging in tumor-prone transgenic mice to identify
collaborating oncogenes and genes contributing to tumor progression. This has
yielded a series of oncogenes that could be assigned to different complementation
groups in transformation: the myc, Pim, Bmi1, and Frat1 complementation groups.
Frat1 is involved in tumor progression and appears to function in the Wnt
signaling pathway. Overexpression of Fratl confers a growth advantage to
transplanted tumor cells in vivo and to cells grown in vitro at high density.
Frat1 might exert its activity by impairing the kinase activity of Gsk3beta,
which is involved in the degradation of beta-catenin. Pim genes appear to act in
tumor initiation and show strong synergism with myc in lymphomagenesis.
Overexpression of Pim1 can also overcome some of the proliferative defects caused
by defective interleukin signaling supporting a role of Pim1 in cell
proliferation. We have applied proviral tagging in compound mutant Emu-myc/Pim1-/
/Pim2-/- mice to identify genes that can complement for the loss of Pim1 and Pim2
and, therefore, are able to synergize with c-myc in lymphomagenesis. A number of
new as well as known genes have been found by this "complementation tagging." The
latter included c-kit, Tp12, and cyclin D2, suggesting that Pim kinases might act
upstream of or parallel to these known proto-oncogenes.
PMID- 10197596
TI - Role of TCL1 and ALL1 in human leukemias and development.
AB - We have investigated the role of chromosomal translocations in the pathogenesis
of human leukemias. The study of T-cell chronic lymphocytic leukemias and T-cell
prolymphocytic leukemia has led to the identification of TCL1, a novel gene that
is deregulated by translocations, t(14;14)(q11;q32), or inversions,
inv(14)(q11;q32.1). Introduction of a human TCL1 gene juxtaposed to the Ick
promoter into fertilized mouse eggs resulted in the development of transgenic
mice that developed mature T-cell leukemias, indicating that TCL1 is a
transforming oncogene. We have also investigated acute leukemias with
abnormalities at chromosome 11q23. We have identified a gene, ALL1, that can fuse
to many different genes in acute leukemias. We have also shown that ALL1 can fuse
with ALL1 in acute myelogenous leukemia. We have proposed that the ALL1 fusion
genes may act by a dominant negative mechanism.
PMID- 10197597
TI - Intersections between blood cell development and leukemia genes.
AB - Hematopoietic development is regulated in large part by transcription factors
that control cell fate decisions and cellular differentiation. Several genes
first discovered in the context of chromosomal translocations in leukemia also
serve important functions in blood cell development. Gene-targeting experiments
related to two of these factors, SCL/tal-1 and translocation-ets-leukemia (TEL),
are reviewed here. SCL/tal-1, a T-cell basic helix-loop-helix oncoprotein, is
required for the formation of all hematopoietic lineages. In addition, it is
essential for angiogenesis in the yolk sac, indicating a dual function in blood
and vessel development. TEL, an ets-related factor which is translocated to a
variety of other genes in leukemias, is also required for proper angiogenesis in
the yolk sac. Additional studies, however, demonstrate that TEL function is
necessary for hematopoiesis to be established in the bone marrow
microenvironment. These studies emphasize the intrinsic roles of leukemia
associated transcription factors in normal blood cell and vessel development.
PMID- 10197598
TI - Core-binding factor: a central player in hematopoiesis and leukemia.
AB - Consistent chromosomal rearrangements are found in a large number of
hematopoietic tumors. In many cases, these rearrangements disrupt genes whose
normal function is required for the proper development of blood cells. Excellent
examples are the chromosomal rearrangements t(8;21)(q22;q22), t(12;21)(p13;q22),
and inv(16)(p13q22) that disrupt two of the genes encoding a small family of
heterodimeric transcription factors, core-binding factors (CBFs). CBFs consist of
a DNA-binding CBFalpha subunit and a non-DNA-binding CBFbeta subunit. The
t(8;21), associated with de novo acute myeloid leukemias, disrupts the CBFA2
(AML1) gene, which encodes a DNA-binding CBFalpha subunit. The t(12;21), the most
common translocation in pediatric acute lymphocytic leukemias, also disrupts
CBFA2. The CBFB gene, which encodes the non-DNA-binding subunit of the CBFs, is
disrupted by the inv(16) in de novo acute myeloid leukemias. All chromosomal
rearrangements involving the CBFA2 and CBFB genes create chimeric proteins, two
of which have been unequivocally demonstrated to function as transdominant
negative inhibitors of CBF function. Both the Cbfa2 and Cbfb genes are essential
for normal hematopoiesis in mice, because homozygous disruption of either gene
blocks definitive hematopoiesis. Recent data suggest that Cbfa2 and Cbfb are
required for the emergence of definitive hematopoietic stem cells in the embryo
from a putative definitive hemangioblast precursor. The transdominant negative
inhibitor of CBF created by the inv(16), when present from the beginning of
embryogenesis, also blocks the emergence of definitive hematopoietic cells in the
embryo. On the other hand, chromosomal translocations involving the CBFA2 and
CBFB genes in leukemias block hematopoiesis at later steps. This may reflect a
difference in the timing at which translocations are acquired in the leukemias,
which presumably is subsequent to emergence of the definitive hematopoietic stem
cell. The cumulative data suggest that although the earliest requirement for
Cbfa2 and Cbfb is for emergence of definitive hematopoietic stem cells, both
genes are also required at later stages in the differentiation of some
hematopoietic lineages.
PMID- 10197599
TI - The effect of chromosomal translocations in acute leukemias: the LMO2 paradigm in
transcription and development.
AB - Two general features have emerged about genes that are activated after
chromosomal translocations in acute forms of cancer. The protein products of
these genes are transcription regulators and are involved in developmental
processes, and it seems that the subversion of these normal functions accounts
for their role in tumorigenesis. The features of the LMO family of genes, which
encode LIM-domain proteins involved in T-cell acute leukemia through chromosomal
translocations, typify these abnormal functions in tumorigenesis. For example,
the LMO2 protein is involved in the formation of multimeric DNA-binding
complexes, which may vary in composition at different stages of hematopoiesis and
function to control differentiation of specific lineages. In T cells, enforced
expression of Lmo2 causes aberrant protein complex formation that primarily seems
to hinder the T-cell differentiation program. These observations underscore the
conclusion that protein-protein interaction (in this case, through the LIM
domain) is a key determinant in tumorigenesis. Furthermore, the study of
chromosomal translocations as naturally occurring mutations has been informative
about mechanisms in hematopoiesis as well as in tumor etiology.
PMID- 10197600
TI - Apoptosis, p53, and tumor cell sensitivity to anticancer agents.
AB - A widely held tenet of present day oncology is that tumor cells treated with
anticancer agents die from apoptosis, and that cells resistant to apoptosis are
resistant to cancer treatment. We suggest, in this review, that this tenet may
need to be reexamined for human tumors of nonhematological origin, for two
principal reasons: (a) cell killing has often been assessed in short term assays
that are more influenced by the rate, than the overall level, of cell killing.
This has tended to underestimate cell killing for cells not susceptible to
apoptosis or having mutant p53; and (b) conclusions from experiments with normal
cells transformed with dominant oncogenes have often been extrapolated to tumor
cells. This does not take into account the fact that tumor cells have invariably
undergone selection to an apoptotically resistant phenotype. In this review, we
examine the impact of these two factors with particular emphasis on the influence
of mutations in p53 on the sensitivity of tumor cells to DNA-damaging agents. We
find that because wild-type p53 predisposes cells to a more rapid rate of cell
death after DNA damage, particularly with normal or minimally transformed cells,
that short-term assays have led to the conclusion that mutations in p53 confer
resistance to genotoxic agents. On the other hand, if clonogenic survival is used
to assess killing in cells derived from actual solid human tumors, then apoptosis
and the genes controlling it, such as p53 and bcl-2, appear to play little or no
role in the sensitivity of these cells to killing by anticancer drugs and
radiation.
PMID- 10197601
TI - Increased expression of cyclooxygenase-2 in rat lung tumors induced by the
tobacco-specific nitrosamine 4-(methylnitrosamino)-4-(3-pyridyl)-1-butanone: the
impact of a high-fat diet.
AB - Aberrant or excessive expression of cyclooxygenase (COX)-2 has been implicated in
the pathogenesis of many disease processes, including carcinogenesis. COX-2
expression was immunohistochemically examined in archival samples (D. Hoffmann et
al., Cancer Res., 53: 2758-2761, 1993) of lung neoplasms (adenomas,
adenocarcinomas, and adenosquamous carcinomas) induced by 4-(methylnitrosamino)-1
(3-pyridyl)-1-butanone (NNK) in male F344 rats that had been fed either a
semipurified AIN-76A diet with high-fat (HF; 23.5% corn oil) or low-fat (LF; 5%
corn oil) content. The intensity and extent of COX-2 positivity was graded from 0
(undetectable or negligible expression) to grades 1 (<30% expression), 2 (30-60%
expression), 3 (60-90% expression), and 4 (>90% expression). The scoring criteria
were similar to those used with specimens from human lung cancers (T. Hida et
al., Cancer Res., 58: 3761-3764, 1998). In group 1 (NNK plus HF diet), adenomas,
adenocarcinomas, and adenosquamous carcinomas were of mean grades 2, 3, and 4,
respectively; in group 2 (NNK plus LF diet), the corresponding mean grades were
1, 1, and 3. Although control rats, given HF (group 3) or LF (group 4) diets but
no NNK, developed spontaneous lung tumors, the expression of COX-2 was either
negligible (one adenoma of grade 0 in group 3) or of a very low grade (one
adenocarcinoma of grade 1 in group 4). In addition, the latency of the tumors in
the peripheral lung in assays with NNK is significantly shorter in rats
maintained on the HF diet than in those on LF diet. COX-2 expression was not
evident in normal lung tissues. We report here for the first time that NNK
induces increasingly higher levels of COX-2 expression with progressive stages of
lung tumorigenesis when rats are fed the HF diet. The increase in COX-2
expression may be associated with the development of lung tumors induced by NNK.
This well-defined animal model is valuable for studying modulation of COX-2
expression in lung carcinogenesis by various factors, including dietary
components.
PMID- 10197602
TI - Heterogeneous nuclear ribonucleoprotein B1 as a new marker of early detection for
human lung cancers.
AB - Heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 is an RNA binding protein
that is required for maturation of mRNA precursor. Tockman et al. previously
reported that hnRNP A2/B1 with a M(r) of 31,000 is overexpressed from the early
clinical stage of human lung cancer (M. S. Tockman et al., J. Clin. Oncol., 6:
1685-1693, 1988). However, when hnRNP A2/B1 mRNA and hnRNP B1 mRNA were
separately studied, we found unique evidence that hnRNP B1 mRNA, which is a
splicing variant of hnRNP A2 mRNA, was more significantly elevated in lung cancer
tissues than hnRNP A2/B1 mRNA. Our hnRNP B1-specific polyclonal antibody
specifically recognized hnRNP B1 protein as a M(r) 37,000 nuclear protein by
Western blotting but did not recognize hnRNP A2 protein. Immunohistochemical
staining with the hnRNP B1 antibody revealed that hnRNP B1 protein was
specifically stained in the nuclei of human cancer cells, and in squamous cell
carcinomas in particular, but not in those of normal adjacent lung epithelial
cells. We think that hnRNP B1 protein of M(r) 37,000, not hnRNP A2, is well
qualified as a biomarker for the detection of human lung cancer.
PMID- 10197603
TI - Localization of PS6K to chromosomal region 17q23 and determination of its
amplification in breast cancer.
AB - The application of comparative genomic hybridization to the analysis of genetic
abnormalities in breast carcinoma has consistently revealed that chromosome
region 17q22-24 is a frequent site of gene amplification in this type of cancer.
As part of an examination of expressed sequence tags for novel amplified genes in
this region, we identified PS6K amplifications in both breast tumor tissues and
cell lines. PS6K was localized to 17q23 and encodes a serine-threonine kinase
whose activation is thought to regulate a wide array of cellular processes
involved in the mitogenic response including protein synthesis, translation of
specific mRNA species, and cell cycle progression from G1 to S phase. Northern
and Western analyses revealed that amplification of this gene was accompanied by
corresponding increases in mRNA and protein expression, respectively. These data
represent the first determination of a gene amplification within 17q22-24 in
breast cancer and suggest an oncogenic activity for PS6K.
PMID- 10197604
TI - Comparison of cytochrome P450- and peroxidase-dependent metabolic activation of
the potent carcinogen dibenzo[a,l]pyrene in human cell lines: formation of stable
DNA adducts and absence of a detectable increase in apurinic sites.
AB - The potent carcinogen dibenzo[a,l]pyrene (DB[a,l]P) has been reported to form
both stable and depurinating DNA adducts upon activation by cytochrome P450
enzymes and/or cellular peroxidases. Only stable DB[a,l]P-DNA adducts were
detected in DNA after reaction of DB[a,I]P-11,12-diol-13,14-epoxides in solution
or cells in culture. To determine whether DB[a,l]P can be activated to
metabolites that form depurinating adducts in cells with either high peroxidase
(human leukemia HL-60 cell line) or cytochrome P450 activity (human mammary
carcinoma MCF-7 cell line), cultures were treated with DB[a,l]P for 4 h, and the
levels of stable adducts and apurinic (AP) sites in the DNA were determined. DNA
samples from DB[a,l]P-treated HL-60 cells contained no detectable levels of
either stable adducts or AP sites. MCF-7 cells exposed to 2 microM DB[a,l]P for 4
h contained 4 stable adducts per 10(6) nucleotides, but no detectable increase in
AP sites. The results indicate that metabolic activation of DB[a,l]P by
cytochrome P450 enzymes to diol epoxides that form stable DNA adducts, rather
than one-electron oxidation catalyzed either by cytochrome P450 enzymes or
peroxidases to form AP sites, is responsible for the high carcinogenic activity
of DB[a,l]P.
PMID- 10197605
TI - Superiority of yeast over bacterial cytosine deaminase for enzyme/prodrug gene
therapy in colon cancer xenografts.
AB - The enzyme/prodrug strategy using bacterial cytosine deaminase (bCD) and 5
fluorocytosine (5-FC) is currently under investigation for cancer gene therapy. A
major limitation for the use of bCD is that it is inefficient in the conversion
of 5-FC into 5-fluorouracil. In the present study, we show that the K(m) of yeast
cytosine deaminase (yCD) for 5-FC was 22-fold lower when compared with that of
bCD. HT29 human colon cancer cells transduced with yCD (HT29/yCD) were
significantly more sensitive to 5-FC in vitro than HT29 cells transduced with bCD
(HT29/bCD). In tumor-bearing nude mice, complete tumor regression was observed in
6 of 13 HT29/yCD tumors in response to 5-FC treatment (500 mg/kg i.p. daily, 5
days a week for 2 weeks), whereas 0 of 10 HT29/bCD tumors were cured. Our study
demonstrates an improved efficacy of the CD/5-FC treatment strategy when yCD was
used. This enzyme has, therefore, a high potential to increase the therapeutic
outcome of the enzyme/prodrug strategy in cancer patients.
PMID- 10197606
TI - Caspase-mediated degradation of T-cell receptor zeta-chain.
AB - We recently reported an association between loss in T-cell receptor (TcR) zeta
chain expression and tumor-induced apoptosis of T lymphocytes. In this study, the
possibility that zeta-chain serves as a direct substrate for activated caspases
was investigated. Here, we report that two DXXD motifs, which are putative
recognition sequences for caspase-3-related proteases and are present in the
amino acid sequence of the zeta-chain, are cleaved in apoptotic Jurkat T
lymphocytes. Cleavage of zeta-chain in Jurkat cells ligated by agonistic anti-Fas
antibody was inhibited in the presence of peptide inhibitors of caspases,
including the pan-caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl
ketone and N-benzyloxycarbonyl-Asp-Glu-Val-Asp-fluoromethyl ketone, an inhibitor
of caspase-3-like activity. Fas-induced cleavage of zeta-chain was also inhibited
in Jurkat cells overexpressing the intracellular inhibitors of caspase activity,
Bcl-2 or cytokine response-modifier A. In vitro translated zeta-chain was cleaved
in a similar fashion by recombinant caspase-3 or caspase-7 in a dose-dependent
manner. In the presence of N-benzyloxycarbonyl-AspGlu-Val-Asp-fluoromethyl
ketone, no cleavage of in vitro translated zeta-chain was observed. These results
suggest that the loss of TcR zeta-chain, previously associated with tumor-induced
immune dysfunction and more recently associated with tumor-induced apoptosis of T
lymphocytes, is mediated by a direct degradation of the zeta-chain by activated
caspases. This is the first report of involvement of caspases in degradation of
the zeta protein.
PMID- 10197607
TI - Differential transactivation by alternative EWS-FLI1 fusion proteins correlates
with clinical heterogeneity in Ewing's sarcoma.
AB - The t(11;22)(q24;q12) translocation is present in up to 95% of cases of Ewing's
sarcoma and results in the formation of an EWS-FLI1 fusion gene which encodes a
chimeric transcription factor. The proximate role of EWS-FLI1 in the pathogenesis
of Ewing's sarcoma is thought to involve the activation of as yet largely unknown
target genes. Many alternative forms of EWS-FLI1 exist because of variations in
the locations of the EWS and FLI1 genomic breakpoints. The most common form,
designated "type 1," consists of the first seven exons of EWS joined to exons 6-9
of FLI1 and accounts for approximately 60% of cases. The "type 2" EWS-FLI1 fusion
also includes FLI1 exon 5 and is present in another 25%. We and others have
observed previously that the type 1 fusion is associated with a significantly
better prognosis than the other fusion types. Because EWS-FLI1 is an aberrant
transcription factor, we investigated whether these differences in clinical
behavior may be correlated to functional differences by comparing transactivation
by the type 1 EWS-FLI1 with other types in both heterologous cells (HeLa, NIH3T3)
and homologous cells (Ewing's sarcoma cell lines). In a panel of seven Ewing's
sarcoma cell lines, we found transactivation of a transiently transfected FLI1
responsive reporter construct to be significantly lower in cell lines with the
type 1 fusion than in cell lines with the type 2 fusion (P = 0.003).
Cotransfection of the same reporter construct with each of a series of seven EWS
FLI1 expression constructs (corresponding to the two major fusion types and five
less common types) also showed that type 1 EWS-FLI1 was a significantly weaker
transactivator than the type 2 product in both HeLa and NIH3T3 cells (P = 0.003,
and P = 0.033, respectively). Electromobility shift assays showed equivalent
binding of the type 1 and type 2 EWS-FLI1 to the consensus FLI1-responsive
binding site, indicating that differences in transactivation were not due simply
to differences in DNA binding affinity. The finding that the type 1 EWS-FLI1
fusion, associated with less aggressive clinical behavior, encodes a less active
chimeric transcription factor may provide the basis for a molecular explanation
of clinical heterogeneity in Ewing's sarcoma.
PMID- 10197608
TI - Comparative genomic hybridization of breast tumors stratified by histological
grade reveals new insights into the biological progression of breast cancer.
AB - How does breast cancer progress? There is evidence both to support (S. W. Duffy
et al., Br. J. Cancer, 64: 1133-1138, 1991; R. Rajakariar et al., Br. J. Cancer,
71: 150-154, 1995) and refute (M. Hakama et al., Lancet, 345: 221-224, 1995; R.
R. Millis et al., Eur. J. Cancer, 34: 548-553, 1998) the hypothesis of
dedifferentiation; the theory that as breast cancers grow they evolve from well
differentiated (grade I) to poorly differentiated (grade III) tumors. We provide
evidence to support the view that the majority of grade I tumors do not progress
to grade III tumors. Comparative genomic hybridization was used to screen entire
genomes of a large sample (40 grade I and 50 grade III) of invasive ductal breast
carcinomas, stratified by grade. We found distinct genetic differences between
grade I and grade III tumors. Significantly, we found that 65% of grade I tumors
lost the long arm of chromosome 16 compared with only 16% of grade III tumors.
This pattern of loss leads us to conclude that the majority of grade I tumors do
not progress to grade III tumors. These findings have important implications
because they suggest that different breast tumor grades may have distinct
molecular origins, pathogenesis, and behavior and, therefore, potentially present
distinct molecular targets for research and treatment.
PMID- 10197609
TI - Allelotype of gastric adenocarcinoma.
AB - Gastric adenocarcinoma is a leading cause of cancer mortality world-wide. Yet,
the underlying molecular events important in the development of this cancer are
largely undefined. Thus, we performed a comprehensive survey for allelic loss on
our panel of xenografted human gastric carcinomas. Contaminating normal stromal
cells of primary cancers often limit mutational analyses. Xenografted samples of
our gastric carcinomas provided optimally enriched tumors for neoplasia that
clearly and sensitively demonstrated genetic alterations. Additionally, total
absence of allelic signals in these xenografted samples confirmed true loss of
alleles rather than just allelic imbalance. Analysis of at least two highly
polymorphic microsatellite markers per nonacrocentric chromosomal arm in our
xenografted human gastric carcinomas demonstrated significant loss of
heterozygosity well above background levels at 3p, 4p, 5q, 8p, 9p, 13q, 17p, and
18q. Several of these loci represent novel findings of significant loss in
gastric cancers. On chromosome 17p, p53 is known to be inactivated either by
mutation or deletion in a majority of gastric carcinomas. The critical target(s)
of inactivation in gastric cancers at these other loci remain to be
characterized.
PMID- 10197610
TI - Beta-catenin mutations are more frequent in small colorectal adenomas than in
larger adenomas and invasive carcinomas.
AB - Loss of serine or threonine phosphorylation sites from exon 3 of beta-catenin has
been identified in approximately half of colorectal tumors which lack adenomatous
polyposis coli (APC) mutations, but the overall contribution of beta-catenin
mutations to sporadic colorectal tumorigenesis is unclear. We therefore used PCR
to amplify and sequence exon 3 of beta-catenin from 202 sporadic colorectal
tumors. Exon 3 beta-catenin mutations were identified in 6 of 48 small (< 1 cm)
adenomas, 2 of 82 large (> or =1 cm) adenomas, and 1 of 72 invasive carcinomas.
Eight of the nine mutations, including all of those in the small adenomas and the
invasive cancer, involved loss of serine or threonine phosphorylation sites. The
percentage of beta-catenin mutations in small adenomas (12.5%) was significantly
greater than that in large adenomas (2.4%) and invasive cancers (1.4%; P = 0.05
and P = 0.02, respectively). We conclude that mutation of beta-catenin can be an
early, perhaps initiating, event in colorectal tumorigenesis. Small adenomas with
beta-catenin mutations do not appear to be as likely to progress to larger
adenomas and invasive carcinomas as other adenomas, however, with the result that
beta-catenin mutations are only rarely seen in invasive cancers. This suggests
that APC and beta-catenin mutations are not functionally equivalent, and that the
APC gene may have other tumor suppressor functions besides the degradation of
beta-catenin.
PMID- 10197611
TI - Novel genes in the PAGE and GAGE family of tumor antigens found by homology
walking in the dbEST database.
AB - We have developed a computer-based screening strategy to search the dbEST
database to find differentiation antigens that are expressed by cancers arising
in nonessential normal tissues such as prostate, breast, and ovary (G. Vasmatzis
et al., Proc. Natl. Acad. Sci. USA, 95: 300-304, 1998). Here, we report the
identification of three new members of the GAGE/ PAGE family, termed XAGEs. XAGE
1 and XAGE-2 are expressed in Ewing's sarcoma, rhabdomyosarcoma, a breast cancer,
and a germ cell tumor. We also describe the relationship of the XAGEs to the
GAGE/ PAGE family. XAGE-1 and XAGE-2 should be evaluated as possible targets for
vaccine-based therapies of cancer.
PMID- 10197612
TI - Antiapoptotic signaling in LNCaP prostate cancer cells: a survival signaling
pathway independent of phosphatidylinositol 3'-kinase and Akt/protein kinase B.
AB - Constitutive activation of the phosphatidylinositol 3'-kinase (PI3 kinase)
Akt/protein kinase B (PKB) "survival signaling" pathway is a likely mechanism by
which many cancers become refractory to cytotoxic therapy. In LNCaP prostate
cancer cells, the PTEN phosphoinositide phosphatase is inactivated, leading to
constitutive activation of Akt/PKB and resistance to apoptosis. However,
apoptosis and inactivation of Akt/PKB can be induced in these cells by treatment
with PI3 kinase inhibitors. Surprisingly, androgen, epidermal growth factor, or
serum can protect these cells from apoptosis, even in the presence of PI3 kinase
inhibitors and without activation of Akt/PKB, indicating the activity of a novel,
Akt/PKB-independent survival pathway. This pathway blocks apoptosis at a level
prior to caspase 3 activation and release of cytochrome c from mitochondria.
PMID- 10197613
TI - Cremophor EL-mediated alteration of paclitaxel distribution in human blood:
clinical pharmacokinetic implications.
AB - We have determined the in vitro and in vivo cellular distribution of the
antineoplastic agent paclitaxel (Taxol) in human blood and the influence of
Cremophor EL (CrEL), the vehicle used for i.v. drug administration. In the
absence of CrEL, the blood:plasma concentration ratio was 1.07+/-0.004 (mean+/
SD). The addition of CrEL at concentrations corresponding to peak plasma levels
achieved after the administration of paclitaxel (175 mg/m2 i.v. over a 3-h
period; ie., 0.50%) resulted in a significant decrease in the concentration ratio
(0.690+/-0.005; P < 0.05). Kinetic experiments revealed that this effect was
caused by reduced erythrocyte uptake of paclitaxel by polyoxyethyleneglycerol
triricinoleate, the major compound present in CrEL. Using equilibrium dialysis,
it was shown that the affinity of paclitaxel for tested matrices was (in
decreasing order) CrEL > plasma > human serum albumin, with CrEL present at or
above the critical micellar concentration (approximately 0.01%). Our findings in
the present study demonstrate a profound alteration of paclitaxel accumulation in
erythrocytes caused by a trapping of the compound in CrEL micelles, thereby
reducing the free drug fraction available for cellular partitioning. It is
proposed that the nonlinearity of paclitaxel plasma disposition in patients
reported previously should be reevaluated prospectively by measuring the free
drug fractions and whole blood:plasma concentration ratios.
PMID- 10197614
TI - The anticancer prodrug CPT-11 is a potent inhibitor of acetylcholinesterase but
is rapidly catalyzed to SN-38 by butyrylcholinesterase.
AB - Patients treated with high doses of CPT-11 rapidly develop a cholinergic syndrome
that can be alleviated by atropine. Although CPT-11 was not a substrate for
acetylcholinesterase (AcChE), in vitro assays confirmed that CPT-11 inhibited
both human and electric eel AcChE with apparent K(i)s of 415 and 194 nM,
respectively. In contrast, human or equine butyryl-cholinesterase (BuChE)
converted CPT-11 to SN-38 with K(m)s of 42.4 and 44.2 microM for the human and
horse BuChE, respectively. Modeling of CPT-11 within the predicted active site of
AcChE and BuChE corroborated experimental results indicating that, although the
drug was oriented correctly for activation, the constraints dictated by the
active site gorge were such that CPT-11 would be unlikely to be activated by
AcChE.
PMID- 10197615
TI - Induction of vascular endothelial growth factor expression in endothelial cells
by platelet-derived growth factor through the activation of phosphatidylinositol
3-kinase.
AB - Increased numbers of platelet-derived growth factor beta receptors betaPPDGFRs)
on neovascular endothelial cells is a common occurrence in several pathological
conditions including wound healing, inflammation, and glioma tumorigenesis. Here
we sought to test the biological significance of this by determining whether
expression of wild-type betaPDGFR by normal aortic endothelial cells affected the
expression of the vascular endothelial growth factor (VEGF), a critical
angiogenesis regulator and mitogen for such cells. The results showed that PDGF
could increase transcription and secretion of VEGF by betaPDGFR-expressing
endothelial cells. Moreover, we further demonstrated a requirement for the
activation of phosphatidylinositol 3-kinase (PI3K) in this response by using
chemical inhibitors of PI3K, mutant PDGFR, and dominant-negative PI3K. These
studies suggest a novel mechanism by which PDGF induces VEGF expression in
endothelial cells, define VEGF as a downstream target for PI3K, and invoke a role
for PI3K in angiogenesis.
PMID- 10197616
TI - Comparative metabolism of 1-, 2-, and 4-nitropyrene by human hepatic and
pulmonary microsomes.
AB - Determining the capability of humans to metabolize the mononitropyrene (mono-NP)
isomers 1-, 2-, and 4-NP and understanding which human cytochrome P450 (P450)
enzymes are involved in their activation and/or detoxification is important in
the assessment of individual susceptibility to these environmental carcinogens.
We compared the ability of 15 human hepatic and 8 pulmonary microsomal samples to
metabolize each of the three isomers. Human hepatic microsomes were competent in
metabolizing all three isomers. Qualitatively similar metabolic patterns were
observed, although at much lower levels, upon incubating mono-NP with pulmonary
microsomes. Ring-oxidized metabolites (phenols and trans-dihydrodiols) were
produced from all three isomers. However, the nitroreductive metabolism leading
to the formation of aminopyrene was evident only with 4-NP. The role of specific
P450 enzymes in the human hepatic microsomal metabolism of mono-NP was
investigated by correlating the P450-dependent catalytic activities in each
microsomal sample with the levels of individual metabolites formed by the same
microsomes and by examining the effects of agents that can either inhibit or
stimulate specific P450 enzymes in mono-NP metabolism. On the basis of these
studies, we attribute most of the hepatic microsomal metabolism of 1- and 4-NP to
P450 3A4, although a minor role for P450 1A2 cannot be ruled out. Specifically,
P450 3A4 was responsible for the formation of 3-hydroxy-1nitropyrene from 1-NP
and the formation of trans-9,10-dihydro-9,10dihydroxy-4-nitropyrene, 9(10)
hydroxy-4-nitropyrene, and 4-aminopyrene from 4-NP. None of the P450 enzymes
examined (P450s 3A4, 1A2, 2E1, 2A6, 2D6, and 2C9) appeared to be involved in
catalyzing the formation of trans-4,5-dihydro-4,5-dihydroxy-2-nitropyrene and 6
hydroxy-2-nitropyrene from 2-NP in human hepatic microsomes. These results, the
first report on the comparative metabolism of mono-NP in humans, clearly
demonstrate that the role of specific human P450 enzymes in catalyzing oxidative
and reductive pathways of mono-NP is dependent upon the position of the nitro
group.
PMID- 10197617
TI - Increased chromosome-type chromosome aberration frequencies as biomarkers of
cancer risk in a blackfoot endemic area.
AB - To examine whether biomarkers such as sister chromatid exchanges (SCEs) and
chromosome aberrations (CAs) can predict cancer development, a nested case
control study was performed in a blackfoot endemic area with a known high cancer
risk. A cohort of 686 residents was recruited from three villages in the
blackfoot endemic area. Personal characteristics were collected, and venous blood
was drawn for lymphocyte culture and stored in a refrigerator. The vital status
and cancer development were followed using the National Death Registry, Cancer
Registry, and Blackfoot Disease Registry. The follow-up period was from August
1991 to July 1995. During this 4-year period, 31 residents developed various
types of cancer. Blood culture samples from nine of these subjects were
unsuitable for experiments due to improper storage. Finally, a total of 22 cancer
cases had cytogenetic samples that could be analyzed. Twenty-two control subjects
were selected from those who did not develop cancer in the study period, and
these subjects were matched to cases by sex, age, smoking habits, and residential
area. The results showed that there was no significant difference in the
frequencies of SCE and chromatid-type CAs between the case and control groups.
However, the frequencies of chromosome-type CAs, e.g., chromosome-type gaps,
chromosome-type breaks, chromosome-type breaks plus exchanges, total chromosome
type aberrations, and total frequencies of CAs in the case group, were
significantly higher than those in the control group (P < 0.05). The odds ratio
of cancer risk in subjects with more than zero chromosome-type breaks was 5.0
(95% confidence interval = 1.09-22.82) compared to those with zero chromosomal
breaks. The odds ratios for more than zero chromosome-type breaks plus exchanges
and a frequency of total chromosome-type aberrations of >1.007% were 11.0 and
12.0, respectively (P < 0.05). Subjects with a total CA frequency of >4.023% had
a 9-fold increase for cancer risk. These results indicate that chromosome-type
CAs are good biomarkers for the prediction of cancer development, whereas SCEs
and chromatid-type CAs cannot predict cancer risk.
PMID- 10197618
TI - Induction of lytic Epstein-Barr virus (EBV) infection in EBV-associated
malignancies using adenovirus vectors in vitro and in vivo.
AB - The consistent presence of EBV genomes in certain tumor types (in particular,
AIDS-related central nervous system lymphomas and nasopharyngeal carcinomas) may
allow novel, EBV-based targeting strategies. Tumors contain the latent
(transforming) form of EBV infection. However, expression of either of the EBV
immediate-early proteins, BZLF1 and BRLF1, is sufficient to induce lytic EBV
infection, resulting in death of the host cell. We have constructed replication
deficient adenovirus vectors expressing the BZLF1 or BRLF1 immediate-early genes
and examined their utility for killing latently infected lymphoma cells in vitro
and in vivo. We show that both the BZLF1 and BRLF1 vectors efficiently induce
lytic EBV infection in Jijoye cells (an EBV-positive Burkitt lymphoma cell line).
Furthermore, lytic EBV infection converts the antiviral drug, ganciclovir (GCV),
into a toxic (phosphorylated) form, which inhibits cellular as well as viral DNA
polymerase. When Jijoye cells are infected with the BZLF1 or BRLF1 adenovirus
vectors in the presence of GCV, viral reactivation is induced, but virus
replication is inhibited (thus preventing the release of infectious EBV
particles); yet cells are still efficiently killed. Finally, we demonstrate that
the BZLF1 and BRLF1 adenovirus vectors induce lytic EBV infection when they are
directly inoculated into Jijoye cell tumors grown in severe combined
immunodeficiency mice. These results suggest that induction of lytic EBV
infection in tumors, in combination with GCV, may be an effective strategy for
treating EBV-associated malignancies.
PMID- 10197619
TI - Use of alanosine as a methylthioadenosine phosphorylase-selective therapy for T
cell acute lymphoblastic leukemia in vitro.
AB - Methylthioadenosine phosphorylase (MTAP) is an important enzyme for the salvage
of adenine and methionine and is deficient in a variety of cancers including T
cell acute lymphocytic leukemia (T-ALL). Previously, we reported that the MTAP
gene was deleted in over 30% of T-ALL patients at both diagnosis and relapse. We
now report that MTAP-primary T-ALL cells are more sensitive to the toxicity of L
alanosine, an inhibitor of de novo AMP synthesis, than are MTAP+ primary T-ALL
cells. As measured by [3H]thymidine incorporation, DNA synthesis in all seven
MTAP-primary T-ALL cells was inhibited by L-alanosine with a mean IC50 of 4.8+/
5.3 ILM (range, 0.3-11.3 microM). On the other hand, the IC50 for 60% (12 of 20)
of MTAP+ primary T-ALL was 19+/-18 microM (range, 1.7-67 microM; P = 0.02),
whereas the remaining 40% (8 of 20) had an IC50 of >80 microM4. Furthermore,
normal lymphocytes and MTAP+ primary T-ALL cells were rescued from L-alanosine
toxicity by the MTAP substrate 5'-deoxyadenosine, but MTAP-T-ALL cells were not.
These results indicate that normal cells, which are intrinsically MTAP+, would be
protected from L.-alanosine toxicity, whereas MTAP-tumor cells would be killed.
Thus, our results support the use of L-alanosine alone or in combination with a
salvage agent as a MTAP-selective therapy and therefore lay the foundation for
the initiation of clinical trials for the treatment of T-ALL and other MTAP
deficient malignancies with L-alanosine.
PMID- 10197620
TI - Identification of the transcriptional regulatory sequences of human kallikrein 2
and their use in the construction of calydon virus 764, an attenuated replication
competent adenovirus for prostate cancer therapy.
AB - Human glandular kallikrein (hK2) and prostate-specific antigen (PSA) are related
members of the human kallikrein gene family. The genes for hK2 and PSA are
expressed predominately in the prostate, are transcriptionally up-regulated by
androgens, and share 78% homology. Previously, one functional androgen response
element was identified within the proximal promoter (-324 to +33 relative to the
cap site) of the hK2 gene. To detect additional upstream regulatory elements, the
12.3 kbp between the PSA gene and 5' to the hK2 gene were amplified by PCR and
linked to a promoterless firefly luciferase reporter gene. Transient transfection
experiments showed an androgen-dependent enhancer, located between -3.4 and -5.2
kb upstream of the transcription start site of the hK2 gene. This hK2 enhancer
increased luciferase expression 100-fold in the presence of the testosterone
analogue R1881. The hK2 enhancer contains an androgen response element that lost
activity when mutated. The hK2 enhancer/promoter demonstrated activity in PSA(+)
LNCaP cells whereas the enhancer/promoter was inactive in PSA(-) 293, A549,
HBL100, HUH-7, LoVo, MCF-7, OVCAR-3, and PC-3 cells. Insertion of the hK2
enhancer/promoter into adenovirus to drive the E1A genes of adenovirus type 5
(Ad5) created an attenuated replication competent adenovirus variant Calydon
virus (CV) 763, which replicates similarly to wild-type adenovirus in prostate
tumor cells but is attenuated in nonprostate tumor cells. In addition, CV764, an
adenovirus variant containing the previously cloned prostate-specific enhancer
(to drive the Ad5 E1A genes) and the hK2 enhancer/promoter (to drive the Ad5 E1B
genes) was constructed. CV764 is significantly attenuated and has a high
therapeutic index with a cell specificity of 10,000:1 for PSA(+) LNCaP cells,
compared to ovarian cancer OVCAR-3 cells and SK-OV-3 cells and PA-1 cells. CV764
is also highly attenuated in primary human microvascular endothelial cells.
PMID- 10197621
TI - Development of meta-tetrahydroxyphenylchlorin-monoclonal antibody conjugates for
photoimmunotherapy.
AB - A limitation of photodynamic therapy is the lack of tumor selectivity of the
photosensitizer. To overcome this problem, a protocol was developed for coupling
of meta-tetrahydroxyphenylchlorin (mTHPC), one of the most promising
photosensitizers, to tumor-selective monoclonal antibodies (MAbs). mTHPC was
radiolabeled with 131I to facilitate the assessment of the in vitro and in vivo
behavior. After the modification to 131I-mTHPC-(CH2COOH)4, thus increasing the
water solubility and creating a functional moiety suitable for coupling,
conjugation was performed using a labile ester. Insoluble aggregates were not
formed when mTHPC-MAb conjugates with a molar ratio of up to 4 were prepared.
These conjugates showed a minimal impairment of the integrity on SDS-PAGE, full
stability in serum in vitro, and an optimal immunoreactivity. To test the in vivo
behavior of the mTHPC-MAb conjugates, the head and neck squamous cell carcinoma
selective chimeric MAb U36 was used in head and neck squamous cell carcinoma
bearing nude mice. Biodistribution data showed that the tumor selectivity of cMAb
U36-conjugated mTHPC was increased in comparison with free mTHPC, despite the
fact that conjugates with a higher mTHPC:MAb ratio were more rapidly cleared from
the blood. Preliminary results on the in vitro efficacy of photodynamic therapy
with MAb-conjugated mTHPC showed that mTHPC coupled to the internalizing murine
MAb 425 exhibited more phototoxicity than when coupled to the noninternalizing
chimeric MAb U36.
PMID- 10197622
TI - Alteration of the conserved residue tyrosine-158 to histidine renders human O6
alkylguanine-DNA alkyltransferase insensitive to the inhibitor O6-benzylguanine.
AB - The DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT) protects cells
from alkylation damage. O6-Benzylguanine (BG) is a potent inactivator of human
AGT (ED50 of 0.1 microM) that is currently undergoing clinical trials to enhance
chemotherapy by alkylating agents. In a screen of AGT mutants randomly mutated at
position glycine-160, we found that the double mutant Y158H/G160A protected
Escherichia coli from killing by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) even
in the presence of BG and that the AGT activity of this mutant was strongly
resistant to BG (ED50 of 180 microM). Because the single mutant G160A was not
resistant to BG, this suggested that the presence of the charged histidine
residue at position 158 was responsible. This hypothesis was confirmed by the
construction of the single mutation Y158H. The Y158H-mutant AGT was slightly less
active than wild-type AGT for the repair of methylated DNA in vitro, but it
protected E. coli from killing by MNNG even in the presence of BG and had an ED50
for the inactivation by BG of 620 microM. In contrast, mutant Y158F had an ED5o
of 0.2 microM. Previous studies (M. Xu-Welliver et al., Cancer Res., 58: 1936
1945, 1998) have shown that mutant P140K is highly resistant to BG (ED50 of >1200
microM). Models of human AGT suggest that the side chain of the lysine inserted
into this mutant is close to tyrosine-158 and that the positively charged lysine
side-chain may interfere with BG binding. The double mutants P140K/Y158H and
P140K/Y158F resembled P140K and Y158H in being highly resistant to BG, but the
use of a sensitive assay for reaction of BG with AGT indicated that their
abilities to react were in the order P140K/ Y158H < P140K < P140K/Y158F. These
results confirm that the presence of a positively charged residue close to the
active site of human AGT renders it highly resistant to BG without substantially
affecting activity toward methylated DNA substrates. Such mutants may limit the
value of BG therapy if they arise in malignant cells during chemotherapy, but the
mutant sequences may be useful for gene therapy approaches in which BG-resistant
human AGTs are used to prevent hematopoietic toxicity. At least 28 AGT sequences
(from 25 species) have now been described. In 25 of these, the position
equivalent to 158 in the human AGT is also a tyrosine, and in the other 3, it is
a phenylalanine. The importance of an aromatic ring side chain at this position
is emphasized by previous studies (S. Edara et al., Carcinogenesis, 16: 1637
1642, 1995), which show that the replacement by alanine renders human AGT
inactive. Our results show that histidine can also substitute for tyrosine at
this position.
PMID- 10197623
TI - A fully synthetic immunogen carrying a carcinoma-associated carbohydrate for
active specific immunotherapy.
AB - Aberrant glycosylation of mucins leads to the exposure of cryptic carbohydrate
antigens at the surface of carcinoma cells, which, therefore, represent potent
targets for anticancer therapeutic vaccines. To date, the development of
immunogens to stimulate immune response to such saccharidic antigens is based on
carbohydrate conjugation to carrier proteins. However, these traditional protein
conjugates are poorly defined in chemical composition and structure. As an
alternative, we synthesized a multiple antigenic O-linked glycopeptide (MAG)
carrying the carbohydrate Tn antigen associated with a CD4+ T-cell epitope
(MAG:Tn-PV). This fully synthetic immunogen is highly defined in composition and
carries a high saccharidic epitope ratio over the entire molecule. The MAG:Tn-PV
was able to induce anti-Tn IgG antibodies that recognize human tumor cell lines.
A therapeutic immunization protocol performed with this fully synthetic immunogen
increased the survival of tumor-bearing mice. Thus, the accurately defined and
versatile MAG system represents an efficient strategy to induce carbohydrate
specific antitumor immune responses but may also be applicable to the prevention
of infectious diseases, if it is based on bacterial oligosaccharides.
PMID- 10197624
TI - Enhancement of graft-versus-tumor activity and graft-versus-host disease by
pretransplant immunization of allogeneic bone marrow donors with a recipient
derived tumor cell vaccine.
AB - Allogeneic bone marrow transplantation (BMT) can be accompanied by a beneficial T
cell-mediated antitumor immune response known as graft-versus-tumor (GVT)
activity. However, BMT donor T cells are not exposed to target antigens of GVT
activity until transfer to the host, where tumor antigen presentation may be
suboptimal. This study tested in a murine model the hypothesis that immunization
of MHC-matched allogeneic donors with a recipient-derived tumor cell vaccine
would substantially increase GVT activity and extend survival of BMT recipients
with preexisting micrometastatic tumor. C3H.SW and C57BL/10 mice were immunized
against a C57BL/6-derived fibrosarcoma or leukemia, and they were used as BMT
donors. Recipients were H-2-matched, minor histocompatibility antigen-mismatched
C57BL/6 mice with previously established micrometastatic tumors. Donor
immunization led to a significant increase in GVT activity that was T cell
dependent and cell dose dependent. In some settings, donor immunization also
prolonged survival of recipients with preexisting micrometastatic tumors.
However, donor immunization significantly increased the incidence of fatal graft
versus-host disease such that long-term survival was uncommon. In vitro
cytotoxicity assays indicated that donor immunization induced both tumor
selective and alloreactive cytolytic T-cell populations. In vivo cross-protection
assays showed that a substantial portion of the GVT effect was mediated by
alloreactive cells not specific for the immunizing tumor. In conclusion,
immunization of allogeneic BMT donors with a recipient-derived whole tumor cell
vaccine substantially increases GVT activity but also exacerbates graft-versus
host disease.
PMID- 10197625
TI - A critical role for a peritumoral stromal reaction in the induction of T-cell
migration responsible for interleukin-12-induced tumor regression.
AB - Interleukin (IL) 12 has been shown to elicit tumor regression when this cytokine
induces the migration of T cells to tumor sites. The present study investigates
the role of a peritumoral stromal reaction in IL-12-induced T-cell migration. In
the CSA1M and OV-HM tumor models, IL-12 treatment induced tumor regression that
is associated with T-cell migration. Neither T-cell migration nor tumor
regression was observed in the Meth A and MCH-1-A1 models. Stromal tissue
containing neovascular blood vessels developed at the peritumoral area of the
former two IL-12-responsive tumors but not at the peritumoral area of the latter
two IL-12-unresponsive tumors. The significance of stroma development was
investigated using a pair of tumor models (CSA1M and a subline derived from CSA1M
designated the CSA1M variant), both of which exhibit the same tumor
immunogenicity. In contrast to the parental CSA1M cell line, the variant cell
line was not responsive to IL-12, and neither stroma development nor T-cell
migration was observed, even after IL-12 treatment. Histological analyses
revealed that the parental cell line had peritumoral stroma with intrastromal
vessels but only a few vessels in tumor parenchyma, whereas the variant cell line
showed no stroma but had abundant vasculature in the tumor parenchyma. Most
importantly, only stromal vessels in the parental tumors expressed detectable and
enhanced levels of vascular cell adhesion molecule 1 (VCAM-1)/ intercellular
adhesion molecule 1 (ICAM-1) before and after IL-12 treatment, respectively. In
contrast, parenchymal vasculature in the variant cell line failed to express VCAM
1/ICAM-1 even after IL-12 treatment. When transferred into recipient tumor
bearing mice, IL-12-stimulated T cells from the parental CSA1M-bearing or the
variant CSA1M-bearing mice migrated into the parental but not into the variant
tumor mass. Together with our previous finding that T-cell migration depends on
the VCAM-1/ICAM-1 adhesive interactions, the present results indicate a critical
role for peritumoral stroma/stromal vasculature in the acceptance of tumor
infiltrating T cells that is a prerequisite for IL-12-induced tumor regression.
PMID- 10197626
TI - Expression of catalytically active telomerase does not prevent premature
senescence caused by overexpression of oncogenic Ha-Ras in normal human
fibroblasts.
AB - All normal cells in culture display a limited capacity to divide and eventually
undergo an irreversible growth arrest known as replicative cellular senescence.
The development of cellular immortality has been implicated as an important
factor in the progression of human cancers. Expression of telomerase has been
shown to elicit a bypass of senescence and the acquirement of an extended life
span. Although oncogenic Ras induces malignant transformation in most immortal
cells, it has been shown to cause a senescence-like cell cycle arrest in
presenescent human fibroblasts. To test the relationship between the senescence
inducing effect of Ras and the senescence-bypassing activity of telomerase, we
used retroviral vector infection to introduce the catalytic subunit of human
telomerase into normal human lung fibroblasts. Cell clones displaying in vitro
telomerase catalytic activity and life span extension were obtained. However,
these cells still became senescent after infection with a retrovirus vector
expressing oncogenic Ha-Ras. No differences in premature senescence phenotypes
between normal and telomerase-expressing cells were observed. A small number of
colonies were recovered after the introduction of Ha-Ras into either normal or
telomerase-expressing cells, but in all cases, these clones failed to express the
exogenously introduced Ras. We propose that even in the presence of active
telomerase, the cellular senescence machinery remains intact and can be activated
by appropriate signals. Consequently, interventions aimed at the activation of
the latent senescence program may be a fruitful approach in cancer therapy.
PMID- 10197627
TI - Cells deficient in DNA polymerase beta are hypersensitive to alkylating agent
induced apoptosis and chromosomal breakage.
AB - DNA polymerase beta (beta-pol), which is involved in base excision repair, was
investigated for its role in protection of cells against various genotoxic agents
and cytostatic drugs using beta-pol knockout mouse fibroblasts. We show that
cells lacking beta-pol are highly sensitive to induction of apoptosis and
chromosomal breakage by methylating agents, such as N-methyl-N'-nitro-N
nitrosoguanidine and methyl methanesulfonate and the cross-linking antineoplastic
drugs mitomycin C and mafosfamide. The cross-sensitivity between the agents
observed suggests that beta-pol is involved in repair not only of DNA methylation
lesions but also of other kinds of DNA damage induced by various cytostatic
drugs. Cells deficient in beta-pol were not hypersensitive to cisplatin,
melphalan, benzo(a)pyrene diol epoxide, chloroethylnitrosourea, or UV light.
Because both established and primary beta-pol knockout fibroblasts displayed the
hypersensitive phenotype, which, moreover, was complemented by transfection with
a beta-pol expression vector, the alkylating agent hypersensitivity can clearly
be attributed to the beta-pol deficiency. The results demonstrate that beta-pol
driven base excision repair is highly important for protection of cells against
cell killing due to apoptosis and induced chromosomal breakage and suggest that
incompletely repaired DNA damage causes chromosomal changes and may act as a
trigger of DNA damage-induced apoptosis.
PMID- 10197628
TI - The breast cancer-associated MUC1 gene generates both a receptor and its cognate
binding protein.
AB - MUC1 proteins, some of which contain a mucin-like domain and others lacking this
region, can be generated from the human breast cancer-associated MUC1 gene by
alternative splicing. The MUC1/Y isoform is devoid of the mucin domain and is a
cell membrane protein that undergoes transphosphorylation on both serine and
tyrosine residues. We have identified cognate binding proteins that specifically
interact with the extracellular domain of MUC1/Y. Coimmunoprecipitation analyses
clearly revealed the presence of complexes composed of MUC1/Y and its cognate
binding proteins in primary breast tumor tissue. MUC1/Y-expressing mammary tumor
cells can be specifically targeted, in vivo, with the labeled cognate binding
protein. The k(D) of MUC1/Y for its binding proteins was estimated as 1.2 nM. The
MUC1/Y binding proteins are also derived from the MUC1 gene and represent the
secreted mucin-like polymorphic MUC1 proteins MUC1/SEC and MUC1/REP, which
contain a tandem repeat array. Whereas nonposttranslationally modified MUC1/Y
bound efficiently to MUC1/SEC, the latter mucin-like protein had to be
posttranslationally modified in a cell-type specific manner to bind MUC1/Y. The
interaction of MUC1/Y with MUC1/SEC has important biological functional
correlates: (a) it induces MUC1/Y phosphorylation; and (b) it has a pronounced
effect on cell morphology. These findings suggest that MUC1/Y and MUC1/SEC form
an active receptor/ cognate binding protein complex that can elicit cellular
responses. The proteins comprising this complex are, thus, generated by
alternative splicing from one and the same gene, namely the MUC1 gene.
PMID- 10197629
TI - Chromosome 13q deletion mapping in pituitary tumors: infrequent loss of the
retinoblastoma susceptibility gene (RB1) locus despite loss of RB1 protein
product in somatotrophinomas.
AB - Two recent studies have described allelic loss of an RB1 intragenic marker on
chromosome 13q in aggressive and metastatic pituitary tumors that did not
correlate with loss of pRB. The second report also showed that losses were more
frequently associated with a more centromeric marker. Because both of these
studies suggest the presence of another or other tumor suppressor genes (TSGs) on
13q, we carried out an allelotype analysis encompassing known and recently
described TSG loci on 13q, together with immunohistochemical analysis of pRB. We
analyzed 82 nonfunctional tumors and 53 somatotrophinomas subdivided into
invasive and noninvasive cohorts. A significantly higher frequency of loss, at
one or more of 13 markers, was evident in the invasive nonfunctional tumors (54%,
26 of 48) than in their noninvasive counterparts (29%, 10 of 34). An
approximately equal frequency of loss was apparent in invasive (28%, 5 of 18) and
noninvasive (31%, 11 of 35) somatotrophinomas at one or more markers. In those
tumors harboring deletion, loss at two or more markers was more frequent in
invasive nonfunctional tumors 65% (17 of 26) compared with 36% (4 of 11) of their
noninvasive counterparts. In somatotrophinomas, 40% (2 of 5) of invasive tumors
as compared with 64% (7 of 11) of noninvasive tumors had evidence of two or more
deletions. In tumors showing loss at two or more loci, the majority showed large
deletions; however, loss of the RB1 intragenic marker D13S153 was infrequent. In
most cases, loss at individual markers was more frequent in invasive tumors than
their noninvasive counterparts. A marker 3 cM telomeric to RB1 (D13S1319) showed
the highest frequency of deletion in both invasive cohorts (29% of
somatotrophinomas and 24% of nonfunctional tumors). Immunohistochemical analysis
of pRB showed frequent loss in somatotrophinomas (27%, 9 of 33) in comparison
with 4% (2 of 53) of non-functional tumors. Although loss of pRB did not
correlate with loss of an intragenic marker or tumor grade, it was significantly
associated with the somatotrophinoma subtype (P = 0.002). These data suggest that
chromosome 13q is a frequent target for allelic deletion in pituitary tumors and
point to another or other TSG loci in these regions.
PMID- 10197630
TI - Plasma DNA microsatellites as tumor-specific markers and indicators of tumor
progression in melanoma patients.
AB - Multiple DNA microsatellites with frequent loss of heterozygosity (LOH) in
melanomas have been demonstrated. The finding that free DNA is enriched in blood
of melanoma patients prompted studies to determine whether tumor-specific DNA,
such as DNA microsatellites exhibiting LOH, can be detected in blood and have
clinical use. In this study, 57 advanced and 19 early clinically staged melanoma
patients were assessed using 10 microsatellite markers on six chromosomes.
Matched plasma and melanoma tissues from 40 patients showed significant
concordance of LOH (P < 0.0001). The frequency of LOH microsatellite markers
detected in plasma significantly increased in more advanced-staged patients. At
locus D3S1293, LOH detection showed significant correlation to clinical disease
progression (P = 0.02). Additionally, the combination of LOH microsatellite
markers D9S157 and D3S1293 (P = 0.01), D9S157 and D1S228 (P = 0.05), and D11S925
and D3S1293 (P = 0.01) were significantly correlated to progression of different
clinical stages of disease. These studies indicate that tumor-specific LOH
markers in plasma have a potential clinical use as diagnostic and prognostic
markers in melanoma patients.
PMID- 10197632
TI - Hypoxia-induced up-regulation of angiogenin in human malignant melanoma.
AB - Angiogenesis is essential for tumor progression and metastasis, however, the
angiogenesis regulators that are biologically relevant for human melanoma are
still unknown. In this study, we analyzed the expression of the potent angiogenic
factor angiogenin (ANG) in human melanoma in vitro and in vivo. Four different
human melanoma cell lines and two normal melanocytes were kept either under
normoxic or hypoxic conditions. After 24 h of hypoxic culture conditions, ANG was
up-regulated in the melanoma cell lines but not in normal melanocytes. Induction
levels correlated with the metastatic potential of the cell lines. These data
were confirmed by Northern blot analysis. In contrast, induction of vascular
endothelial growth factor by hypoxia was equally strong in the examined highly
aggressive melanoma cell lines and in one nonaggressive cell line. Other
angiogenic factors tested as well as the melanoma growth stimulatory activity
(Gro-alpha) showed no up-regulation. Thus, in the present study, hypoxia-induced
up-regulation in melanoma cells was only observed for ANG and vascular
endothelial growth factor. Immunohistochemical studies showed that 8 of 10
melanomas and all 15 metastases were positive for ANG, particularly in the
vicinity of small vessels, whereas all benign nevi were negative. Reverse
transcription-PCR detected only weak ANG mRNA in nevi but strong signals in
primary melanomas and metastases. In conclusion, we demonstrate for the first
time enhanced expression of ANG in highly metastatic cell lines as well as in
melanomas and metastases in vivo, suggesting that ANG expression is associated
with the metastatic potential.
PMID- 10197631
TI - Transcriptional activation of cyclooxygenase-2 in Wnt-1-transformed mouse mammary
epithelial cells.
AB - Wnt-1 acts as a mammary oncogene when ectopically expressed in the mouse mammary
gland. APC is a tumor suppressor gene, mutations in which cause intestinal
tumorigenesis in humans and rodents. Both Wnt-1 expression and APC mutation
activate a common signaling pathway involving transcriptional activation mediated
by beta-catenin/Tcf complexes, but few targets relevant to carcinogenesis have
yet been identified. Expression of the inducible prostaglandin synthase
cyclooxygenase-2 appears critical for intestinal tumorigenesis resulting from APC
mutation, suggesting that cyclooxygenase-2 might be a transcriptional target for
beta-catenin/Tcf complexes. Here, we have investigated the effect of Wnt-1 on
cyclooxygenase-2 expression. Wnt-1 expression in the mouse mammary epithelial
cell lines RAC311 and C57MG induces stabilization of cytosolic beta-catenin and
morphological transformation. Expression of Wnt-1 in these cells caused
transcriptional up-regulation of the cyclooxygenase-2 gene, resulting in
increased levels of cyclooxygenase-2 mRNA and protein. Prostaglandin E2
production was increased as a consequence of the elevated cyclooxygenase-2
activity and could be decreased by treatment with a selective cyclooxygenase-2
inhibitor. Cyclooxygenase-2 thus appears to be a common downstream target for APC
mutation and Wnt-1 expression. In view of the critical role of cyclooxygenase-2
in intestinal tumorigenesis, cyclooxygenase-2 up-regulation in response to Wnt
signaling may contribute to Wnt-induced mammary carcinogenesis.
PMID- 10197633
TI - Initiation of growth arrest and apoptosis of MCF-7 mammary carcinoma cells by
tributyrin, a triglyceride analogue of the short-chain fatty acid butyrate, is
associated with mitochondrial activity.
AB - We investigated the effects of tributyrin, a triglyceride analogue of the short
chain fatty acid butyrate and an approved food additive, establishing induction
of growth arrest and apoptosis of MCF-7 human mammary carcinoma cells. Transient
increased mitochondria-associated bax, dissipation of the mitochondrial membrane
potential (delta(psi)m), and caspase-3-independent cleavage of poly(ADP-ribose)
polymerase are evident as early as 4 h after treatment of cells with tributyrin.
These events are followed by the transient accumulation of mitochondrial
cytochrome c in the cytosol and, finally, the generation and accumulation of
cells with subdiploid DNA content. During the period in which mitochondria
associated bax levels are elevated, the delta(psi)m is disrupted, and cytochrome
c is detected in the cytosol, we show induction of p21WAF1/Cip1 in the absence of
increased p53 and arrest of cells in G2-M. Thus, early mitochondria-associated
events may play a key role in initiating and/or coordinating tributyrin-mediated
growth arrest and apoptosis of wild-type p53 MCF-7 cells. Because effective
chemoprevention has been associated with agents that restore or maintain the
balance between proliferation and apoptosis, dietary tributyrin, particularly
during the critical period of mammary gland development, may be a promising
chemopreventive agent.
PMID- 10197634
TI - Tumor-derived expression of vascular endothelial growth factor is a critical
factor in tumor expansion and vascular function.
AB - There is considerable controversy concerning the importance of tumor-derived
angiogenic factors to the neovascularization of solid tumors. Tumor, endothelial,
and stromal expression of vascular endothelial growth factor (VEGF) have been
hypothesized to be critical for tumor angiogenesis. To determine the relative
contribution of tumor versus nontransformed tissue expression of VEGF to tumor
growth, we used gene targeting and cre-loxP recombination to generate embryonic
stem cell lines in which VEGF can be conditionally deleted. These lines were used
to derive mouse embryonic fibroblast lines with null mutations in both alleles of
VEGF. Upon immortalization and H-ras transformation, we used these VEGF null
fibroblasts to make fibrosarcomas in immunocompromised mice. We report that
tumorigenic VEGF expression is critical for ras-mediated tumorigenesis, and the
loss of tumorigenic expression causes dramatic decreases in vascular density and
vascular permeability and increases in tumor cell apoptosis.
PMID- 10197635
TI - Profile of cytokine expression in nasopharyngeal carcinomas: a distinct
expression of interleukin 1 in tumor and CD4+ T cells.
AB - Nasopharyngeal carcinoma (NPC) is an epithelial cancer that is causally
associated with Epstein-Barr virus (EBV) infection. NPC tumor biopsies are
characterized histopathologically by an abundant infiltration of nonmalignant
lymphocytes. We analyzed the expression of various cytokines in NPC tissues to
investigate the interaction of the infiltrating lymphocytes and tumor cells.
Analysis using reverse transcriptase-PCR revealed the expression of a panel of
cytokines in the NPC biopsies: interleukin (IL)-1alpha, IL-1beta, IL-2, IL-4, IL
5, IL-6, IL-10, IFN-gamma, tumor necrosis factor-alpha, transforming growth
factor-beta, and IL-1 receptor types I and II. Elevated expression of IL-1alpha
and IL-1beta was observed in primary tumors and NPC metastases compared to
control tissues. Interestingly, this increased expression correlated with the EBV
encoded viral IL-10 transcript. To determine which cells were responsible for
producing IL-1, we determined the cellular constituents of NPC biopsies by
immunoflow cytometric analysis. On the basis of data from these analyses, the
three major specific cell populations, epithelial cells, CD4+ T cells, and CD8+ T
cells, were selected from five NPC tumors using specific, antibody-coated
paramagnetic beads. Reverse transcriptase-PCR of RNA from these fractionated
cells showed that transcripts of IL-1alpha and IL-1beta were present not only in
the malignant epithelial cells but also in CD4+ T cells infiltrating the tumor, a
finding confirmed by immunohistochemical staining. We hypothesize that the
unusual synthesis of IL-1alpha and IL-1beta by EBV-positive epithelial cells as
well as by CD4+ T cells might contribute to lymphocyte infiltration and/or tumor
growth during NPC development.
PMID- 10197636
TI - Tumor necrosis factor-alpha sensitizes prostate cancer cells to gamma-irradiation
induced apoptosis.
AB - LNCaP prostate cancer cells are highly resistant to induction of programmed cell
death by y-irradiation and somewhat sensitive to the death-inducing effects of
tumor necrosis factor (TNF)-alpha. Simultaneous exposure of LNCaP cells to TNF
alpha and 8 Gy of irradiation was synergistic and resulted in a 3-fold increase
of apoptotic cells within 72 h compared to TNF-alpha alone. It appeared that TNF
alpha sensitized the cells to irradiation because, when cells were irradiated 24
h after exposure to TNF-alpha, increased cell death was observed. In contrast,
irradiation delivered 24 h prior to TNF-alpha exposure did not result in more
cell death than after TNF-alpha alone. TNF-alpha induced expression of its own
mRNA, but TNF-alpha mRNA induction was neither induced nor enhanced by
irradiation. Activation of the transcription factor nuclear factor kappaB can be
induced by TNF-alpha and has a modulating antiapoptotic effect. But enhancement
of TNF-alpha-induced cell death by irradiation did not result from altered
activation of nuclear factor kappaB. TNF-alpha treatment of LNCaP cells resulted
in partial activation of caspase-8 and -6 but not caspase-3. There was only
minimal poly(ADP-ribose) polymerase cleavage seen in LNCaP cells after exposure
to both TNF-alpha and irradiation at 72 h, a time when 60% of the cells were
apoptotic. Experiments with peptide inhibitors of cysteine and serine proteases
suggested that caspases were the predominant mediators of apoptosis induced by
TNF-alpha alone but that serine proteases contributed significantly to cell death
induced by TNF-alpha plus irradiation. TNF-alpha increased production of ceramide
in LNCaP cells 48 h after exposure. Although irradiation alone had no effect on
ceramide production in LNCaP cells, TNF-alpha plus irradiation induced
significantly more ceramide than TNF-alpha alone. Ceramide production did not
occur immediately after exposure to TNF-alpha, but rather was delayed such that
ceramide levels were increased only 24 h after exposure to apoptotic stimuli.
Moreover, non-toxic levels of exogenous C2-ceramide sensitized LNCaP cells to
irradiation similarly to TNF-alpha, suggesting that one mechanism by which LNCaP
cells were sensitized to irradiation was by increased intracellular ceramide.
Hence, ceramide generation is a critical component in radiation-induced apoptosis
in human prostate cancer cells. Inhibition of ceramide generation may provide a
selective advantage in the development of radioresistance in prostate cancer.
PMID- 10197637
TI - Intratumoral distribution of two consecutive injections of chimeric antibody G250
in primary renal cell carcinoma: implications for fractionated dose
radioimmunotherapy.
AB - Tumor uptake of the chimeric G250 (cG250) monoclonal antibody (mAb) in patients
with primary renal cell carcinoma (RCC) is among the highest reported in solid
tumors. However, as observed in other tumor types, the intratumoral distribution
of the antibody is highly heterogeneous, which may limit the efficacy of
radioimmunotherapy. A number of highly dynamic physiological factors have been
postulated that may contribute to heterogeneous tumor uptake of antibodies. Their
impact on tumor uptake of antibodies may vary from one tumor region to another as
well as from one day to the next. Here, we report on a clinical study that was
designed to investigate whether the pattern of mAb cG250 uptake within RCC tumors
is altered with subsequent injections. Ten patients with a clinical diagnosis of
primary RCC were studied. Nine days before surgery, patients received 125I-cG250
(5 mg of cG250, 50 microCi of 125I), followed by a second injection of 131I-cG250
(5 mg of cG250, 3.5 mCi of 131I) 4 days later. Postsurgery, the tumor was cut
into (1-cm) thick slices. Slices were imaged on a gamma camera, and the slice
with the most pronounced heterogeneity in 131I-cG250 distribution was selected
and cut into 1-cm3 cubes. Each cube was analyzed for 121I-cG250 and 131I-cG250
uptake, and the 131I/125I ratio was determined. For each tumor slice, the
distribution patterns of both isotopes were reconstructed and compared with each
other. All tumors analyzed showed a heterogeneous distribution of both isotopes
throughout the tumor slice; focal uptake in some areas of a tumor reached very
high levels (up to 0.19% injected dose/g), whereas other tumorous areas of the
same slice showed much lower uptake (as low as 0.0047% injected dose/g).
Remarkably, in all tumors, the distribution pattern of both injections was
identical: without exception, in all samples analyzed (n = 692), the uptake of
125I-cG250 was similar to 131I-cG250 uptake. Overall, the 131I/125I ratio was
1.64+/-0.31 (mean+/-SD). The constant 131I/125I ratios, observed in all tumor
samples investigated, indicate that the tumor parameters governing cG250 mAb
uptake were not altered significantly within the time period studied. In
addition, the results of this study suggest that multiple radiolabeled antibody
injections, administered within short time periods, will target the same areas
within a tumor and, thus, will not solve the problem of heterogeneous tumor
uptake of antibody.
PMID- 10197638
TI - Heregulin beta1-activated phosphatidylinositol 3-kinase enhances aggregation of
MCF-7 breast cancer cells independent of extracellular signal-regulated kinase.
AB - Heregulin (HRG) is a family of polypeptide growth factors derived from
alternatively spliced genes. HRG can bind to receptor tyrosine kinases erbB3 and
erbB4, thereby inducing erbB3 and erbB4 heterodimerization with erbB2, leading to
receptor tyrosine phosphorylation and activating downstream signal transduction.
Cell-cell homophilic adhesion (cell aggregation) is important in determining the
structural organization and behavior of cells in tissues. In addition, tumor cell
homophilic adhesion may affect invasive and metastatic potentials of cells. We
report that HRG-beta1 can enhance aggregation of MCF-7 and SKBR3 human breast
cancer cells. While investigating the downstream signals involved in HRG-beta1
enhanced cell aggregation, we observed that HRG-beta1 induced tyrosine
phosphorylation of erbB2 and crbB3 receptor heterodimers and increased the
association of the dimerized receptors with the 85-kDa subunit of
phosphatidylinositol 3-kinase (PI3K). HRG-beta also increased the kinase
activities of extracellular signal-regulated protein kinase (ERK) and PI3K in
these cells. By using the mitogen-activated protein kinase/ERK 1 (MEK1) inhibitor
PD98059 and PI3K inhibitors wortmannin and LY294002, we found that blocking the
MEK1-ERK pathway had no effect on HRG-pbeta1-enhanced cell aggregation; however,
blocking the PI3K pathway greatly inhibited HRG-beta1-mediated cell aggregation.
Our study indicated that the HRG-beta1-activated MEK1-ERK pathway has no
demonstrable role in the induction of cell aggregation, whereas HRG-beta1
activated PI3K is required for enhancing breast cancer cell aggregation. Because
aggregation can contribute to invasion/metastasis phenotype of cancer cells, our
results have provided one mechanism by which HRG-beta1-activated signaling of
erbB receptors may affect invasive/metastatic properties of MCF-7 and SKBR3
breast cancer cells.
PMID- 10197639
TI - Combretastatin A-4 phosphate as a tumor vascular-targeting agent: early effects
in tumors and normal tissues.
AB - The potential for tumor vascular-targeting by using the tubulin destabilizing
agent disodium combretastatin A-4 3-0-phosphate (CA-4-P) was assessed in a rat
system. This approach aims to shut down the established tumor vasculature,
leading to the development of extensive tumor cell necrosis. The early vascular
effects of CA-4-P were assessed in the s.c. implanted P22 carcinosarcoma and in a
range of normal tissues. Blood flow was measured by the uptake of radiolabeled
iodoantipyrine, and quantitative autoradiography was used to measure spatial
heterogeneity of blood flow in tumor sections. CA-4-P (100 mg/kg i.p.) caused a
significant increase in mean arterial blood pressure at 1 and 6 h after treatment
and a very large decrease in tumor blood flow, which-by 6 h-was reduced
approximately 100-fold. The spleen was the most affected normal tissue with a 7
fold reduction in blood flow at 6 h. Calculations of vascular resistance revealed
some vascular changes in the heart and kidney for which there were no significant
changes in blood flow. Quantitative autoradiography showed that CA-4-P increased
the spatial heterogeneity in tumor blood flow. The drug affected peripheral tumor
regions less than central regions. Administration of CA-4-P (30 mg/kg) in the
presence of the nitric oxide synthase inhibitor, N(omega)-nitro-L-arginine methyl
ester, potentiated the effect of CA-4-P in tumor tissue. The combination
increased tumor vascular resistance 300-fold compared with less than 7-fold for
any of the normal tissues. This shows that tissue production of nitric oxide
protects against the damaging vascular effects of CA-4-P. Significant changes in
tumor vascular resistance could also be obtained in isolated tumor perfusions
using a cell-free perfusate, although the changes were much less than those
observed in vivo. This shows that the action of CA-4-P includes mechanisms other
than those involving red cell viscosity, intravascular coagulation, and
neutrophil adhesion. The uptake of CA-4-P and combretastatin A-4 (CA-4) was more
efficient in tumor than in skeletal muscle tissue and dephosphorylation of CA-4-P
to CA-4 was faster in the former. These results are promising for the use of CA-4
P as a tumor vascular-targeting agent.
PMID- 10197641
TI - Dietary intervention at middle age: caloric restriction but not
dehydroepiandrosterone sulfate increases lifespan and lifetime cancer incidence
in mice.
AB - Dietary manipulations to prevent cancer and other diseases of aging have drawn
broad public and scientific attention. One indicator of this interest is that
dehydroepiandrosterone (DHEA) supplements are widely consumed by those who hope
that this hormone may keep them "younger longer." However, key data to support
this belief are lacking. For example, the influence of DHEA treatment on
spontaneous cancer and life span in healthy, long-lived strains of mice or rats
is unknown. This is in contrast to the situation for caloric restriction (CR),
which is known to oppose cancer development and increase maximum life span in
rodents. To address this issue, we assigned 300 middle age (12-month-old) male
C57BL/6 mice to one of four groups (n = 75 for each group) and evaluated them for
longevity and spontaneous disease patterns. Two groups were fed a normal diet
(ND), and two others were fed a calorie-restricted diet (RD). One ND group and
one RD group were also given 25 microg/ml DHEA sulfate (DHEAS) in their drinking
water. Although urine samples from DHEAS-treated mice contained 10-fold more DHEA
and DHEAS than did samples from unsupplemented mice, DHEAS administration did not
affect body weight, life span, or cancer patterns. The RD lowered body weight by
26% and increased maximum life span by approximately 15%. The incidence of the
most prevalent cancer, plasma cell neoplasm, was higher in RD mice (66%) than in
ND mice (41%). Thus, DHEAS, as administered here, influenced neither cancer nor
longevity at two caloric intakes. In contrast, CR from middle age increased
longevity, the age at which tumor-bearing mice died, and the percentage of mice
dying with cancers, suggesting that CR may retard promotion and/or progression of
existing lymphoid cancers.
PMID- 10197640
TI - Ovarian carcinoma regulation of matrix metalloproteinase-2 and membrane type 1
matrix metalloproteinase through beta1 integrin.
AB - Culturing DOV 13 ovarian carcinoma cells on three-dimensional collagen lattice
but not on thin-layer collagen induces processing of promatrix metalloproteinase
(MMP)-2 to a M(r) 62,000 form, suggesting that multivalent integrin aggregation
may participate in proteinase regulation. To address the role of collagen-binding
integrins in this event, we treated DOV 13 cells with soluble beta1 integrin
antibodies (clones P4C10 or 21C8) or beta1 integrin antibodies immobilized on
latex beads to promote integrin aggregation. Divalent ligation of beta1 integrins
with soluble P4C10 antibodies stimulated expression of pro-MMP-2 and its
inhibitor, tissue inhibitor of metalloproteinase-2, whereas soluble 21C8
antibodies had no effect. Aggregation of beta1 integrins with immobilized 21C8 or
P4C10 antibodies stimulated MMP-dependent pro-MMP-2 activation and accumulation
of a M(r) 43,000 form of membrane type 1 MMP (MT1-MMP), a cell surface activator
of pro-MMP-2, in cell extracts. beta1 integrin-mediated MMP-2 activation required
protein synthesis and tyrosine kinase signaling and was reduced by an inhibitor
of gene transcription. Treatment of control cells with concanavalin A stimulated
MMP-dependent pro-MMP-2 activation and accumulation of M(r) 55,000 and 43,000
forms of MT1-MMP in cell extracts. Addition of either the MMP inhibitor GM-6001-X
or exogenous tissue inhibitor of metalloproteinase-2 to concanavalin A-treated
cells resulted in loss of the M(r) 43,000 form of MT1-MMP and accumulation of the
M(r) 55,000 form of the enzyme in cell extracts, suggesting that the M(r) 43,000
form is a product of MMP-dependent M(r) 55,000 MT1-MMP proteolysis. Together,
these data suggest that beta1 integrin stimulation of pro-MMP-2 activation
involves MT1-MMP posttranslational processing and requires multivalent integrin
aggregation.
PMID- 10197642
TI - Interdependent regulation of intracellular acidification and SHP-1 in apoptosis.
AB - The G protein-coupled receptor agonist somatostatin (SST)-induces apoptosis in
MCF-7 human breast cancer cells. This is associated with induction of wild-type
p53, Bax, and an acidic endonuclease. We have shown recently that its cytotoxic
signaling is mediated via membrane-associated SHP-1 and is dependent on decrease
in intracellular pH (pHi) to 6.5. Here we investigated the relationship between
intracellular acidification and SHP-1 in cytotoxic signaling. Clamping of pHi at
7.25 by the proton-ionophore nigericin abolished SST-signaled apoptosis without
affecting its ability to regulate SHP-1, p53, and Bax. Apoptosis could be induced
by nigericin clamping of pHi to 6.5. Such acidification-induced apoptosis was not
observed at pHi <6.0 or >6.7. pHi-dependent apoptosis was associated with the
translocation of SHP-1 to the membrane, enhanced in cells overexpressing SHP-1,
and was abolished by its inactive mutant SHP-1C455S. Acidification caused by
inhibition of Na+/H+ exchanger and H+ ATPase (pHi = 6.55 and 6.65, respectively)
also triggered apoptosis. The effect of concurrent inhibition of Na+/H+ exchanger
and H(+)-ATPase on pHi and apoptosis was comparable with that of SST.
Acidification-induced, SHP-1-dependent apoptosis occurred in breast cancer cell
lines in which SST was cytotoxic (MCF-7 and T47D) or not (MDA-MB-231). We
conclude that: (a) SST-induced SHP-1-dependent acidification occurs subsequent to
or independent of the induction of p53 and Bax; (b) SST-induced intracellular
acidification may arise due to inhibition of Na+/H+ exchanger and H(+)-ATPase;
and (c) SHP-1 is necessary not only for agonist-induced acidification but also
for the execution of acidification-dependent apoptosis. We suggest that combined
targeting of SHP-1 and intracellular acidification may lead to a novel strategy
of anticancer therapy bypassing the need for receptor-mediated signaling.
PMID- 10197643
TI - Prostatic carcinoma cell migration via alpha(v)beta3 integrin is modulated by a
focal adhesion kinase pathway.
AB - The highly invasive human prostate cancer PC3 cell line was found to express the
alpha(v)beta3 integrin; in contrast, the noninvasive LNCaP prostate cancer cell
line did not express alpha(v)beta3. PC3 cells adhered to and migrated on
vitronectin (VN), an alpha(v)beta3 ligand expressed in mature bone where prostate
cancer cells preferentially metastasize. In contrast, LNCaP cells did not adhere
to or migrate on VN. Analysis of primary human prostate cancer cells isolated
from 16 surgical specimens, showed that these cells expressed alpha(v)beta3,
whereas normal prostate epithelial cells did not. In addition, only primary
prostate cancer cells adhered to and migrated on VN. The role of alpha(v)beta3 in
mediating prostate epithelial cell migration was confirmed using LNCaP cell
transfectants expressing beta3 (beta3-LNCaP). Exogenous expression of
alpha(v)beta3 induced LNCaP cells to adhere to and migrate on VN. In response to
alpha(v)beta3 engagement, increased tyrosine phosphorylation of focal adhesion
kinase (FAK), a signaling molecule activated by integrins and able to modulate
cell migration, was detected. Transfection of FAK-related nonkinase, known to
compete with FAK for its correct localization and phosphorylation, caused
inhibition of beta3-LNCaP cell migration, specifically on VN. These data indicate
that de novo expression of alpha(v)beta3 integrin in prostate cancer cells
generates a migratory phenotype that is modulated by a FAK signaling pathway.
This study points to alpha(v)beta3 as potential target in prostate cancer cell
invasion and metastasis.
PMID- 10197644
TI - From the University of Washington to Washington University: a personal journey.
PMID- 10197645
TI - Experience with lung transplantation.
AB - BACKGROUND: On the basis of a 5-year experience with heart transplantation and
long-term animal experimentation, a lung transplantation program was instituted
in 1987. After 10 years of experience, the entire patient population was
reviewed. METHODS: Hospital records were reviewed to evaluate the underlying
diagnosis, year of transplantation, type of procedure, and long-term follow-up.
The changing scope of indications, procedures performed, and donor criteria, as
well as survival data for various subgroups of high-risk candidates, were also
examined. RESULTS: A total of 283 heart-lung (n = 46), single-lung (n = 94), and
bilateral lung transplantation procedures (n = 143) were performed, with 22
patients undergoing 24 retransplantation procedures. The overall 5-year survival
rate was 63%, with no difference between types of operations. Patients with
cystic fibrosis, emphysema, pulmonary fibrosis, and secondary pulmonary
hypertension showed similar survival rates; primary pulmonary hypertension was
associated with a lower long-term survival. In all groups, the bronchiolitis
obliterans syndrome occurred at a rate of approximately 15%/year. CONCLUSIONS:
Acceptable long-term results can be obtained with lung transplantation. Because
of expanded indications, no survival benefit was gained in the overall population
over a 10-year period. The major obstacle to true long-term survival remains the
bronchiolitis obliterans syndrome.
PMID- 10197646
TI - Long-segment colon interposition for acquired esophageal disease.
AB - BACKGROUND: Long-segment colon interposition has been used for esophageal
replacement for acquired esophageal disease. The indications for use, morbidity,
and functional results of these conduits have been debated. METHODS: We reviewed
the medical records, office visits, and operative reports of patients undergoing
long colon interposition for acquired esophageal disease at our institution from
1956 to 1997. RESULTS: Long colon interposition was performed in 52 patients for
caustic injury (n = 20), gastroesophageal disease (n = 16), previous irradiation
(n = 8), primary motility disorders (n = 4), and acquired absence of the
esophagus (n = 4). From 1976 to 1997, acquired diseases accounted for 62% of long
colon interposition. The left colon was used in 46 patients and the right colon
in 6. The in-hospital mortality rate was 4%. Early complications included graft
ischemia in 5 patients, anastomotic leak in 3, and small bowel obstruction in 1.
Late complications included anastomotic stenosis requiring dilation in 26
patients, with 2 requiring surgical revision, and bile reflux requiring surgical
diversion in 1 patient. Swallowing function was excellent in 24% of patients,
good in 66%, and poor in 10%. CONCLUSIONS: Long colon interposition can be
performed safely, with acceptable long-term functional results in patients with
acquired esophageal disease.
PMID- 10197647
TI - Esophageal cancer staging: improved accuracy by endoscopic ultrasound of celiac
lymph nodes.
AB - BACKGROUND: Clinical staging of esophageal cancer is required for optimal therapy
but remains imprecise. Pathologic verification of involved lymph nodes could
potentially direct treatment allocation. With the rising incidence of distal and
gastroesophageal junction adenocarcinomas, assessment of the celiac axis lymph
nodes (CLNs) becomes important because it is a common nodal drainage basin.
Endoscopic ultrasound (EUS) permits evaluation of CLNs and biopsy by fine-needle
aspiration. This study examined the usefulness of this staging tool. METHODS: A
consecutive series of 62 patients with esophageal cancer considered resectable by
computed tomographic scan underwent EUS for T and N staging and were
retrospectively studied. A CLN visualized by EUS as greater than 5 mm was
considered positive. Fine-needle aspiration of the CLN was performed routinely.
Endoscopic ultrasound and computed tomographic staging were compared on the basis
of pathologic verification of CLNs. RESULTS: It was possible to evaluate CLNs by
EUS in 59 (95%) of 62 patients: positive in 19, negative in 40. In EUS-positive
patients, fine-needle aspiration was positive in 15, falsely negative in 2, and
not done in 2. By computed tomographic scan, CLNs were negative in 57 patients
and positive in 2. The CLNs were positive in 23 of 54 patients eligible for CLN
pathologic verification. All positive CLNs not identified by EUS (7 false
negative EUS) were microscopic foci in one or two nodes and were associated with
T3 tumors. Sensitivity and specificity of EUS were 72% and 97%, respectively,
compared with 8% and 100% for computed tomographic scan. When EUS identified
CLNs, fine-needle aspiration confirmed positivity in 88% of cases. CONCLUSIONS:
Endoscopic ultrasound with fine-needle aspiration is useful in the detection and
confirmation of CLN metastasis. In T3 tumors of the distal esophagus, a negative
EUS result does not substantiate absence of CLN disease. Endoscopic ultrasound
with fine-needle aspiration may be important in guiding treatment for patients
with distal adenocarcinoma and documenting disease before neoadjuvant therapy.
PMID- 10197648
TI - Pulmonary artery occlusion and reperfusion causes microvascular constriction in
the rabbit lung.
AB - INTRODUCTION: Reperfusion injury of the lung after ischemia is associated with
altered alveolar blood flow and ventilation-perfusion mismatch, which is a
significant cause of morbidity and mortality after lung transplantation. We
examined the effect of ischemia and reperfusion on the tone of individual
subpleural arterioles in the pulmonary circulation by using video microscopy with
polarized epiillumination. METHODS: In 11 open-chested rabbits anesthetized with
pentobarbital (2.3 to 2.5 kg), we ventilated the lungs through the lower trachea
(air or 50% oxygen) and examined the response of subpleural arterioles (diameter
75 +/- 13 microm) to ischemia (76 +/- 32 min) of the right lung caused by
occluding the right main pulmonary artery. Observations were made during
baseline, occlusion, and during early (20 to 32 min) and late (48 to 63 min)
reperfusion using a long working distance lens (550x) with a dipping cone held at
the pleural surface while the lungs were statically inflated (10 cm H2O) with
oxygen for brief periods. Data are expressed as mean +/- standard deviation.
RESULTS: Arteriolar diameter was decreased 57% +/- 19% during early reperfusion.
There was a decrease in blood flow and alveolar walls were pale, indicating
reduced capillary perfusion. During late reperfusion, arteriolar diameter was
diminished (19% +/- 26%); flow was still reduced. Overall pulmonary vascular
resistance increased during early reperfusion but returned to baseline level
during late reperfusion. Arterial partial pressure of oxygen averaged 200 mm Hg
during ischemia and reperfusion. CONCLUSIONS: Constriction of small arterioles by
ischemia and reperfusion can have a significant effect on the early phase of
ventilation-perfusion mismatch and pulmonary dysfunction by altering alveolar
perfusion. This response does not appear to be mediated by hypoxia because it was
not prevented by ventilation with oxygen.
PMID- 10197649
TI - POSSUM scoring system as an instrument of audit in lung resection surgery.
Physiological and operative severity score for the enumeration of mortality and
morbidity.
AB - BACKGROUND: The physiological and operative severity score for the enumeration of
mortality and morbidity (POSSUM) is a scoring system that was validated in
general surgery with the aim of being used as an instrument to evaluate surgical
outcome. We applied POSSUM to a population of lung resection candidates to assess
its capability to predict postoperative complications. METHODS: Two hundred fifty
lung resection candidates were prospectively evaluated from 1993 through 1996.
The POSSUM value was entered along with other variables (sex, smoking history,
type of resection, pulmonary function tests, arterial carbon dioxide, serum
albumin level, total lymphocyte count, neoadjuvant chemotherapy and radiotherapy,
and diabetes) in a multivariate analysis to identify independent predictors of
postoperative morbidity. RESULTS: Logistic regression analysis showed POSSUM was
predictive of postoperative complications, showing no significant difference
between predicted and observed morbidity (chi2 test, p > 0.05). CONCLUSIONS: We
think POSSUM can be appropriately used as a tool of surgical audit in lung
resection operations.
PMID- 10197650
TI - Partial liquid ventilation for acute allograft dysfunction after canine lung
transplantation.
AB - BACKGROUND: This study was designed to investigate the efficacy of partial liquid
ventilation (PLV) on acute allograft dysfunction after lung transplantation.
METHODS: The canine left lung allotransplantation model was used, with the graft
preserved in 4 degrees C low-potassium dextran glucose solution for 18 hours. The
control group (n = 6) had conventional mechanical ventilation, and the PLV group
(n = 6) had perfluorooctylbromide instilled into the airway 30 minutes after
reperfusion. For 360 minutes, allograft function and hemodynamics were evaluated.
After the evaluation, myeloperoxidase activity of the graft tissue was assayed.
RESULTS: All dogs survived for 360 minutes. In the PLV group, PaO2, shunt
fraction, and alveolar to arterial gradient for O2 were significantly better than
those in the control group after 120, 180, and 120 minutes, respectively (p <
0.05). After 240 minutes, peak airway pressure became significantly lower than
that in the control group (p < 0.05). The PaO2 at 360 minutes was 102 +/- 55 mm
Hg in the control group and 420 +/- 78 mm Hg in the PLV group (p < 0.0001), and
the peak airway pressure was 21.4 +/- 4.1 mm Hg in the control group and 14.7 +/-
5.0 mm Hg in the PLV group (p < 0.05). Myeloperoxidase activity in the PLV group
was lower than that in the control group. CONCLUSIONS: The study shows that PLV
alleviated acute allograft dysfunction after lung transplantation.
PMID- 10197651
TI - T4 lung tumors with infiltration of the thoracic aorta: is an operation
reasonable?
AB - BACKGROUND: Only anecdotal reports about the results of combined resection of T4
lung tumors infiltrating the thoracic aorta exist. METHODS: Seven patients (mean
age, 57.5 years; range, 43 to 78 years) underwent a resection of the infiltrated
segment of the thoracic aorta together with a left pneumonectomy (n = 6) or left
upper lobectomy (n = 1). Five tumors were primary non-small cell lung carcinomas
(T4N2 in 3 patients, T4N1 in 2), one was a metastasis of breast cancer, and one
was rhabdomyosarcoma. RESULTS: No patient died perioperatively. The 2 patients
with rhabdomyosarcoma and metastasis of breast cancer died 2 and 7 months
postoperatively. Of the 5 patients with bronchial carcinoma, 3 died after 17, 26,
and 27 months as a result of distant metastasis. Two patients are alive after 14
and 50 months without evidence of disease recurrence. One-year, 2-year, and 4
year survival rates for patients with bronchial carcinoma were 100%, 75%, and
25%, respectively. CONCLUSIONS: Combined resection of the lung and thoracic aorta
can be performed with low morbidity and mortality when offered to highly selected
patients. Adequate local control of tumor can be achieved for N1 and single-level
N2 non-small cell lung carcinomas, but not for tumors with other histologies.
PMID- 10197652
TI - Clinical and hemodynamic performance of the Freestyle aortic root bioprosthesis.
AB - BACKGROUND: The objective of this study is to assess the clinical and hemodynamic
performance of a stentless porcine bioprosthesis, the Freestyle aortic root
bioprosthesis. METHODS: Consenting patients requiring isolated aortic valve or
aortic root replacement received the Freestyle bioprosthesis. Clinical follow-up
and echocardiographic data were obtained at discharge, 3 to 6 months, 1 year, and
annually thereafter. RESULTS: Two hundred seventy-six patients received a
Freestyle aortic root bioprosthesis between January 1993 and July 1997. The mean
age was 67.7 years. Preoperatively, 86.3% were either New York Heart Association
class III or IV. Two hundred thirty-eight patients underwent valve (subcoronary)
replacement, 36 underwent aortic root replacement, and 2 underwent valve
replacement using the root-inclusion technique. The early mortality was 5.4%,
with 3.3% mortality for the subcoronary technique and 19.4% mortality for aortic
root replacement. The mean gradient decreased significantly between discharge and
the 3- to 6-month follow-up and stabilized thereafter. The effective orifice area
increased significantly from discharge to 3 to 6 months' follow-up. At 3 years,
84.4% of the patients had either no or trivial regurgitation. CONCLUSIONS: The
Freestyle bioprosthesis has good clinical performance and good short-term
hemodynamic performance. The majority of the regurgitation identified is not
clinically significant.
PMID- 10197653
TI - Continuous intravenous insulin infusion reduces the incidence of deep sternal
wound infection in diabetic patients after cardiac surgical procedures.
AB - BACKGROUND: Diabetes mellitus is a risk factor for deep sternal wound infection
after open heart surgical procedures. We previously showed that elevated
postoperative blood glucose levels are a predictor of deep sternal wound
infection in diabetic patients. Therefore, we hypothesized that aggressive
intravenous pharmacologic control of postoperative blood glucose levels would
reduce the incidence of deep sternal wound infection. METHODS: In a prospective
study of 2,467 consecutive diabetic patients who underwent open heart surgical
procedures between 1987 and 1997, perioperative blood glucose levels were
recorded every 1 to 2 hours. Patients were classified into two sequential groups:
the control group included 968 patients treated with sliding-scale-guided
intermittent subcutaneous insulin injections (SQI); the study group included
1,499 patients treated with a continuous intravenous insulin infusion in an
attempt to maintain a blood glucose level of less than 200 mg/dL. There were no
differences between these groups with respect to age, sex, procedure, bypass
time, antibiotic prophylaxis, or skin preparation methods. RESULTS: Compared with
subcutaneous insulin injections, continuous intravenous insulin infusion induced
a significant reduction in perioperative blood glucose levels, which led to a
significant reduction in the incidence of deep sternal wound infection in the
continuous intravenous insulin infusion group (0.8% [12 of 1,499]) versus the
intermittent subcutaneous insulin injection group (2.0% [19 of 968], p = 0.01 by
the chi2 test). Multivariate logistic regression revealed that continuous
intravenous insulin infusion induced a significant decrease in the risk of deep
sternal wound infection (p = 0.005; relative risk, 0.34), whereas obesity (p <
0.03; relative risk, 1.06) and use of an internal thoracic artery pedicle (p =
0.1; relative risk, 2.0) increased the risk of deep sternal wound infection.
CONCLUSIONS: Use of perioperative continuous intravenous insulin infusion in
diabetic patients undergoing open heart surgical procedures significantly reduces
major infectious morbidity and its associated socioeconomic costs.
PMID- 10197654
TI - Ultra-fast track hospital discharge using conventional cardiac surgical
techniques.
AB - BACKGROUND: Recent introduction of minimally invasive adult cardiac surgical
techniques has emphasized the advantage of early hospital discharge. However, we
chose an alternative approach to determine the safety, efficacy, and feasibility
of ultra-fast track protocols while retaining both standard surgical exposure
(median sternotomy) and conventional cardiac surgical techniques (hypothermia,
cardiopulmonary bypass with cardiac arrest, and optimal myocardial protection).
METHODS: From September 1995 to January 1998, a total of 258 consecutive patients
underwent cardiac procedures by a single surgeon. Acceleration of clinical
pathways was used to initiate earlier discharges. Stringent postdischarge follow
up was implemented. Prospectively entered data were then analyzed
retrospectively. RESULTS: A variety of isolated as well as combined coronary and
valve procedures were performed. Of the 258 patients operated on during this
entire study period, a total of 144 patients (56%) were discharged within
postoperative days 1 to 4 (ultra-fast track discharge). Over the past 12 months,
this incidence increased to 70% (76 of 108 patients). Approximately 50% of these
patients were operated on urgently or emergently. To date, there have been no
deaths in this ultra-fast track group. There were eight brief readmissions, of
which one was for rewiring of a noninfected sternal dehiscence, and the remaining
were for cardiac diagnostic studies or a noncardiac problem altogether.
CONCLUSIONS: Conventional cardiac operation can allow ultrafast hospital
discharges while retaining the advantage of time-tested techniques and providing
wider application without requiring new or additional training or equipment.
PMID- 10197655
TI - Increased intracerebral excitatory amino acids and nitric oxide after hypothermic
circulatory arrest.
AB - BACKGROUND: Prolonged hypothermic circulatory arrest (HCA) results in neurologic
injury, but the mechanism of this injury is unknown. This study was undertaken to
measure quantitatively intracerebral excitatory amino acids and citrulline, an
equal coproduct of nitric oxide, during HCA. We hypothesized that HCA resulted in
higher levels of glutamate, aspartate, glycine, causing increased intracellular
calcium, and therefore, nitric oxide and citrulline. METHODS: Ten dogs underwent
intracerebral microdialysis and 2 hours of HCA at 18 degrees C. Effluent was
analyzed by high performance liquid chromatography with electrochemical
detection. Five dogs each were sacrificed at 8 and 20 hours after HCA. Neuronal
apoptosis was scored from 0 (no injury) to 100 (severe injury). RESULTS: Time
course of HCA was divided into six periods. Peak levels of amino acids in each
period were compared with those at baseline. Glutamate, coagonist glycine, and
citrulline, an equal coproduct of nitric oxide, increased significantly over
baseline during HCA, cardiopulmonary bypass, and 2 to 8 hours after HCA.
Aspartate increased significantly during HCA and 8 to 20 hours after HCA.
Apoptosis score was 65.56 +/- 5.67 at 8 hours and 30.63 +/- 14.96 at 20 hours
after HCA. CONCLUSIONS: Our results provide direct evidence that HCA causes
increased intracerebral glutamate and aspartate, along with coagonist glycine. We
conclude that HCA causes glutamate excitotoxicity with subsequent nitric oxide
production resulting in neurologic injury, which begins during arrest and
continues until 20 hours after hypothermic circulation arrest. To provide
effective cerebral protection, pharmacologic strategies to reduce glutamate
excitotoxicity require intervention beyond the initial ischemic insult.
PMID- 10197656
TI - Comparison of omental and pectoralis flaps for poststernotomy mediastinitis.
AB - BACKGROUND: Pectoralis flaps are frequently used to treat poststernotomy
mediastinitis. We compared the outcomes of omental transfer, an alternative
treatment for mediastinitis, with those of pectoralis flaps. METHODS: Patients
treated for poststernotomy mediastinitis with isolated omental flaps (n = 21)
were compared with a group of consecutive patients treated with pectoralis flaps
(n = 38). Baseline characteristics were equivalent for the two groups, and both
early and late outcomes were compared. RESULTS: Length of procedure and length of
postoperative hospitalization were reduced significantly and there were
significantly fewer early complications in the group treated with omental flaps.
Furthermore, there were no early or late flap failures or abscesses in the
omental flap group. CONCLUSIONS: This study found that omental flaps had improved
early outcomes and are a more effective therapy relative to pectoralis flaps for
poststernotomy mediastinitis. Technical considerations for omental transfer that
could optimize results are given.
PMID- 10197657
TI - Injury to a patent left internal thoracic artery graft at coronary reoperation.
AB - BACKGROUND: The purpose of this study was to determine the prevalence, outcome,
and operative strategies for patients having injury to a patent left internal
thoracic artery (LITA) graft to the left anterior descending coronary artery
(LAD) at coronary reoperation. METHODS: Of 655 patients with a patent LITA graft
to the LAD undergoing coronary reoperation from 1986 to 1997, 35 (5.3%) sustained
intraoperative injury to the LITA graft. RESULTS: Strategies to restore flow to
the LAD included new saphenous vein graft to the LAD in 15 patients, saphenous
vein graft to the LITA stump in 7, saphenous vein graft to the LAD and repair of
the LITA graft in 6, and other strategies in 7. All or part of the LITA graft to
the LAD was salvaged in 20 patients (57%). Fourteen patients (40%) sustained
perioperative myocardial infarction, and 3 patients died (8.6%). The 3 patients
who died all had stenosis or thrombosis of the graft to the LAD documented at
autopsy. CONCLUSIONS: We conclude that (1) the prevalence of injury to a patent
LITA graft is 5.3%; (2) a variety of techniques can be used to restore blood flow
to the LAD; and (3) ineffective revascularization of the LAD in this situation is
associated with operative mortality. At primary coronary artery bypass grafting,
the LITA pedicle should be positioned in the left chest away from the posterior
sternal table; this strategy may minimize the risk of LITA graft injury at
coronary reoperation.
PMID- 10197658
TI - A survey on partial left ventriculectomy in the Asia-Pacific region.
AB - BACKGROUND: There has been increasing interest in partial left ventriculectomy as
a new therapy for end-stage heart failure. Because the most significant impact of
this development is likely to be in regions where heart transplantation is
largely unavailable, we conducted a survey among a group of cardiac surgeons
based in the Asia-Pacific region to evaluate their overall views on partial left
ventriculectomy procedures. METHODS: A questionnaire was sent to surgeons from 65
major institutions in 17 countries and regions in the Asia-Pacific. Questions
examined current demographics and opinions regarding potential application and
future prospects of this operation. RESULTS: Surveyed surgeons were based in
equal proportions in academic, government, and private practice institutions. One
third of respondents have already performed partial left ventriculectomy
operations, largely in small numbers. In total, 86 procedures were performed with
75% hospital survival rate. Failures were thought to be caused by limited
knowledge about patient selection criteria and lack of experience with operative
technique and perioperative care. The majority of respondents believe that
partial left ventriculectomy is potentially a valuable intervention and intend to
perform more cases. Nevertheless, most surgeons identified the need to have
larger clinical experience, to perform randomized trials against other
therapeutic modalities, and to improve perioperative care. CONCLUSIONS: Although
all surgeons recognize that more knowledge is needed before partial left
ventriculectomy becomes a standard procedure, it is clear from this survey that
the procedure has rapidly gained interest, with more surgeons seeking to learn
it.
PMID- 10197659
TI - Pump prime only aprotinin inhibits cardiopulmonary bypass-induced neutrophil
CD11b up-regulation.
AB - BACKGROUND: The expression of neutrophil integrin CD11b is up-regulated after
cardiopulmonary bypass (CPB) and is the neutrophil adhesive molecule of most
importance in neutrophil- endothelial adherence. This neutrophil-endothelial
adherence is responsible for post-CPB neutrophil-induced reperfusion injury. Low
dose aprotinin protocols inhibit the CPB-induced neutrophil CD11b up-regulation.
This investigation was undertaken to evaluate the effects of pump prime only
aprotinin (280 mg) on the CPB-induced up-regulation of this neutrophil integrin.
METHODS: Twenty-two patients scheduled for elective myocardial revascularization
were randomized into two groups: (1) control (n = 12), or (2) pump prime only
aprotinin (280 mg) (n = 10). Neutrophils were isolated at baseline, 50 minutes of
CPB, and 30 minutes after CPB and neutrophil CD11b expression was measured.
RESULTS: The control group demonstrated a significant (p < 0.05) increase in
neutrophil CD11b immunofluorescent staining at 50 minutes of CPB and at 30
minutes after CPB when compared to same group baseline and to the pump prime only
aprotinin group at similar time intervals. CONCLUSIONS: These results indicate
that pump prime only aprotinin modulates the CPB-induced up-regulation of
neutrophil CD11b integrin, an important indicator of the systemic inflammatory
response to CPB. In addition to blunting of the CPB-induced up-regulation of this
neutrophil integrin expression, this pump prime only dose of aprotinin is also
reported to be effective at reducing post-CPB bleeding and transfusion
requirements. This salutary effect of pump prime only aprotinin suggests that
such low-dose regimens can be both therapeutically effective and cost effective.
PMID- 10197660
TI - Effect of age in the Bypass Angioplasty Revascularization Investigation (BARI)
randomized trial.
AB - BACKGROUND: The influence of age on the relative success of either percutaneous
transluminal coronary angioplasty (PTCA) or coronary artery bypass grafting
(CABG) in patients requiring myocardial revascularization continues to be
controversial. METHODS: In the Bypass Angioplasty Revascularization Investigation
(BARI) trial, 1,829 patients with symptomatic multivessel coronary artery disease
requiring revascularization were randomly assigned to undergo either CABG or
PTCA. RESULTS: Seven hundred nine patients (39%) were 65 to 80 years old at
baseline; the other 1,120 were younger than 65 years. The in-hospital 30-day
mortality rate for PTCA and CABG in the younger patients was 0.7% and 1.1%,
respectively, and that for patients 65 years or older was 1.7% and 1.7%,
respectively. In older compared with younger patients, stroke was more common
after CABG (1.7% versus 0.2%, p = 0.015) and heart failure or pulmonary edema was
more common after PTCA (4.0 versus 1.3%, p = 0.011). In both age groups, CABG
resulted in greater relief of angina and fewer repeat procedures. The 5-year
survival rate in patients younger than 65 years was 91.5% for CABG and 89.5% for
PTCA. In patients 65 years or older, the 5-year survival rate was 85.7% for CABG
and 81.4% for PTCA. Cardiac mortality at 5 years was greater in patients assigned
to the PTCA group than in those assigned to the CABG group. However, no
significant treatment differences were noted in cardiac mortality when only
nondiabetic patients were examined. CONCLUSIONS: Within the context of the Bypass
Angioplasty Revascularization Investigation trial, older patients with
multivessel coronary disease do well with either PTCA or CABG. Compared with
younger patients, older patients had less recurrent angina and were less likely
to undergo repeat procedures, particularly among those assigned to undergo CABG.
Cardiac mortality was greater in patients 65 years or older assigned to undergo
PTCA; however, this difference was not noted when treated diabetic patients were
excluded from analysis.
PMID- 10197661
TI - Identifying patients at low risk of death from cardiac failure after operation
for postinfarct ventricular tachycardia.
AB - BACKGROUND: In unselected patients, cardiac failure accounted for most deaths
after antiarrhythmic operation (ER) for postinfarction ventricular tachycardia
(VT). This study aimed to determine whether patients at low risk of this outcome
could be predicted from a retrospective analysis of variables from 100
consecutive ER patients. METHODS: Thirteen variables suggested by other
researchers as predictive of outcome were analyzed. At the time of study, ER was
the only therapy available for drug refractory VT. RESULTS: Only emergency ER,
wall motion score less than 3 and Killip classification were significantly
related to death from cardiac failure. The lack of correlation between emergency
ER and variables of ER timing, VT less than 24 hours of ER or VT type implies
that the need for emergency ER is also related to ventricular dysfunction.
Multivariate analysis identified a group at particularly low risk of death with a
specificity of 95%. CONCLUSIONS: Patients at low risk of death after ER can be
identified prospectively. In the implantable cardioverter defibrillator era,
elective ER is best reserved for such patients. Emergency ER may still be
justified in younger patients without comorbidity who will die of VT without it.
PMID- 10197662
TI - Medium-term determinants of left ventricular mass index after stentless aortic
valve replacement.
AB - BACKGROUND: This study aimed to investigate the risk factors for elevated left
ventricular mass index 3 to 5 years after stentless aortic valve replacement, and
to elucidate the underlying physiologic mechanisms. METHODS: Eighty-nine patients
(age, 76 +/- 6 years, 51 males) having a stentless porcine valve for aortic
stenosis (n = 76) or regurgitation (n = 13) were prospectively studied by Doppler
echocardiography 3 to 5 years after operation. Left ventricular systolic
function, mass index, blood pressure, cardiac rhythm, and New York Heart
Association function class were all determined. Stentless valve effective orifice
area, mean pressure drop, and the presence and degree of aortic regurgitation
were quantified. RESULTS: The mean stentless aortic valve size was 24 +/- 2 mm.
At follow-up time of 45 +/- 9 months, effective orifice area index was 1.2 +/-
0.35 cm2 x m(-2), and mean pressure drop was 5.7 +/- 3.8 mm Hg. Left ventricular
mass index was 128 +/- 47 g x m(-2), and ejection fraction was 63% +/- 14%.
Multivariant analysis showed a greater left ventricular mass index to be
associated with nonsinus rhythm (versus sinus) (163 +/- 8 versus 131 +/- 7 g x m(
2)), greater pulse pressure (> 84 mm Hg) (161 +/- 7 versus 133 +/- 7 g x m(-2)),
New York Heart Association class II or III (versus class I) (166 +/- 10 versus
128 +/- 5 g x m(-2)), and male sex (versus female) (160 +/- 7 versus 134 +/- 8 g
x m(-2)), all p < 0.01. Mean pressure drop (> 8 mm Hg), effective orifice area
index (< 1.0 cm2 x m(-2)), the presence of mild regurgitation of the stentless
valve, or the type of previous valve disease were insignificant determinants of
left ventricular mass index. CONCLUSIONS: Three to five years after the
implantation, stentless aortic valve hemodynamics remain excellent. Left
ventricular hypertrophy caused by previous native aortic valve disease had
largely regressed. However, patient-related factors, particularly systemic blood
pressure, cardiac rhythm, and function, are significant causes of late residual
left ventricular hypertrophy. Thus, continued medical care and earlier surgical
intervention may further improve the outlook for these patients.
PMID- 10197663
TI - Antiischemic effects of nicardipine and nitroglycerin after coronary artery
bypass grafting.
AB - BACKGROUND: We assessed the efficacy of a continuous infusion of nicardipine and
nitroglycerin in reducing the incidence and severity of perioperative myocardial
ischemia during elective coronary artery bypass grafting procedures in a
prospective, randomized, controlled study. METHODS: Patients received either
nicardipine infusion (0.7 to 1.4 microg x kg(-1) x min(-1); n = 30) or
nitroglycerin (0.5 to 1 microg x kg(-1) x min(-1); n = 30) or neither medication
(n = 17) after aortic occlusion clamp release and for 24 hours postoperatively.
Myocardial ischemic episodes (MIE) were considered to have occurred with ST
segment depressions or elevations of at least 1 mm and at least 2 mm (for both
depressions or elevations), each at J + 60 ms and lasting at least 1 minute,
using a two-channel Holter monitor. RESULTS: Only nicardipine significantly
decreased the duration (p = 0.02) of the 1-mm or greater minutes per hour (3.2 +/
1.2 minutes per hour) and eliminated the number (p = 0.02) of the 2-mm or
greater minutes per hour (zero minutes per hour) when compared with control
patients (17.2 +/- 5.6 minutes per hour and 0.17 minutes per hour, respectively)
during the intraoperative postbypass period. CONCLUSIONS: Our results suggest
that nicardipine lessened the severity of myocardial ischemia shortly after
coronary revascularization and could be considered as an alternative to standard
antiischemic therapy.
PMID- 10197664
TI - Intraoperative arrhythmias and tissue damage during transmyocardial laser
revascularization.
AB - BACKGROUND: Transmyocardial laser revascularization creates transmural channels
to improve myocardial perfusion. Different laser sources and ablation modalities
have been proposed for transmyocardial laser revascularization. We investigated
the incidence of cardiac arrhythmias and laser-tissue interactions during
transmyocardial laser revascularization of normal porcine myocardium with three
different lasers. METHODS: We used a continuous-wave, chopped CO2 laser (20
J/pulse, 15 ms/pulse) synchronized with the R wave; a holmium:yttrium aluminum
garnet (Ho:YAG) laser (2 J/pulse, 250 micros/pulse, 5 Hz); and a xenon-chloride
(excimer, Xe:Cl) laser (35 mJ/pulse, 20 ns/pulse, 30 Hz). Each laser was used 30
times as the sole modality in four consecutive pigs, yielding 120 channels.
RESULTS: The average number of pulses needed to create a channel was 1, 11 +/- 4,
and 37 +/- 8 for the CO2, Ho:YAG, and Xe:Cl lasers, respectively. All Ho:YAG and
Xe:Cl channels had premature ventricular contractions. Ventricular tachycardia
occurred in 70% of the Xe:Cl and 60% of the Ho:YAG channels. Only 36% of the CO2
channels had premature ventricular contractions, and only 3% of the CO2 channels
had ventricular tachycardia (p < 0.001 versus Ho:YAG and Xe:Cl). Ho:YAG channels
were highly irregular: each had a 0.6-mm-wide central zone surrounded by a ring
of coagulation necrosis (diameter, 1.84 +/- 0.67 mm) with effaced cellular
architecture in a thin hemorrhagic zone. The Xe:Cl sections exhibited the same
patterns on a smaller scale (diameter, 0.74 +/- 0.18 mm). The CO2 channels were
straight and well demarcated. The zone of structural and thermal damage extended
over half the channel's diameter, measuring 0.52 +/- 0.25 mm. CONCLUSIONS: During
transmyocardial laser revascularization, the CO2 laser synchronized with the R
wave is significantly less arrhythmogenic than the Ho:YAG and Xe:Cl lasers not
synchronized with the R wave. In addition, the interaction of the CO2 laser with
porcine cardiac tissue is significantly less traumatic than that of the Ho:YAG
and the Xe:Cl lasers.
PMID- 10197665
TI - Transmyocardial laser revascularization: early results and 1-year follow-up.
AB - BACKGROUND: Transmyocardial revascularization using a high-energy CO2 laser has
emerged as a new therapeutic option for patients with severe diffuse coronary
artery disease refractory to conventional modes of therapy. METHODS: From
December 1994 to September 1997, 102 patients underwent isolated transmyocardial
revascularization. The mean age was 56.7 +/- 9.2 years and 92.15% were men. Mean
preoperative angina class and ejection fraction were 2.6 +/- 0.7 and 44.7% +/-
10.5%, respectively. Diabetes was present in 49.01% of patients, 32.3% had
history of previous myocardial infarction, and 12.7% had undergone a previous
coronary artery bypass graft procedure. An average number of 23 +/- 8 channels
were created in each patient using an 800-W CO2 laser. RESULTS: The early
mortality was 14.7% and univariate predictors of mortality were age more than 55
years, female sex, creatine kinase more than 1,600 IU, absence of intercoronary
collaterals, and mean pulmonary artery pressure greater than 21 mm Hg. At 1-year
follow-up there was significant improvement in angina class and effort tolerance
but no significant change in left ventricular ejection fraction. CONCLUSIONS: We
conclude that transmyocardial revascularization provides symptomatic benefit and
improves exercise tolerance in a group of patients suffering from disabling
angina not amenable to other modes of treatment. The high early mortality can be
brought down with strict patient selection criteria. The mechanism of beneficial
effects is uncertain and patency of laser channels is controversial, but laser
induced neoangiogenesis is being looked on as a possible explanation.
PMID- 10197666
TI - Pericardial effusion: subxiphoid pericardiostomy versus percutaneous catheter
drainage.
AB - BACKGROUND: Optimal management of cardiac tamponade resulting from pericardial
effusion remains controversial. METHODS: Cardiac tamponade in 117 patients was
treated with either subxiphoid pericardiostomy (n = 94) or percutaneous catheter
drainage (n = 23). Percutaneous catheter drainage was used for patients with
hemodynamic instability that precluded subxiphoid pericardiostomy. Effusions were
malignant in 75 (64%) of 117 patients and benign in 42 (36%) of 117. RESULTS:
Subxiphoid pericardiostomy had no operative deaths and a complication rate of
1.1% (1 of 94). In contrast, percutaneous drainage had significantly (p < 0.05)
higher mortality and complication rates of 4% (1 of 23) and 17% (4 of 23),
respectively. Patients with an underlying malignancy had a median survival of 2.2
months, with a 1-year actuarial survival rate of 13.8%. In comparison, patients
with benign disease had a median survival of 42.8 months and a 1-, 2-, and 4-year
actuarial survival rate of 79%, 73%, and 49%, respectively (p < 0.05). Effusions
recurred in 1 (1.1%) of 94 patients after subxiphoid pericardiostomy compared
with 7 (30.4%) of 23 patients with percutaneous drainage (p < 0.0001).
CONCLUSIONS: Benign and malignant pericardial tamponade can be safely and
effectively managed with subxiphoid pericardiostomy. Percutaneous catheter
drainage should be reserved for patients with hemodynamic instability.
PMID- 10197667
TI - Variation in hospital rates of intraaortic balloon pump use in coronary artery
bypass operations.
AB - BACKGROUND: Little is known about regional patterns of intraaortic balloon pump
(IABP) use in coronary artery bypass graft (CABG) operations. Our objectives were
(1) to identify clinical variables associated with IABP use, and (2) to examine
risk-adjusted rates of IABP use for 12 Massachusetts hospitals performing CABG
operations. METHODS: We used hospital discharge data to identify 6944 CABG
surgical cases. Logistic regression was used to identify clinical variables
associated with IABP use, and the resulting multivariate model was then used to
risk adjust hospital rates of IABP use. RESULTS: The IABP was used in 13.4% of
the CABG surgical cases. The clinical variables independently associated with
IABP use were cardiogenic shock, same admission angioplasty, prior CABG
operation, cardiac arrest, congestive heart failure, recent myocardial
infarction, and urgent admission status. Risk-adjusted rates of IABP use varied
widely across hospitals from 7.8% to 20.8% (p < 0.0001). CONCLUSIONS: Hospital
rates of IABP use vary considerably in Massachusetts. This practice variation may
be related to the persistent uncertainty regarding the precise clinical
indications for the IABP in this patient population.
PMID- 10197668
TI - Decreased incidence of arterial thrombosis using heparin-bonded intraaortic
balloons.
AB - BACKGROUND: This experimental study sought to determine whether heparin-bonding
of intraaortic balloons (IAB) would decrease the incidence of arterial thrombosis
in the absence of systemic heparinization. METHODS: In 25 adult pigs, a 9F, 40-mL
IAB was inserted into the femoral artery and positioned just below the takeoff of
the left subclavian artery for 9 hours. Five animals received systemic heparin,
10 animals had no heparin, and another 10 animals received no heparin but the IAB
was heparin-bonded (Duraflo II). Thrombus formation was assessed using a
numerical scoring system (0 = no thrombosis to 3 = thrombus >5 cm or evidence of
luminal compromise). RESULTS: Animals receiving heparin and heparin-bonded IAB
had no thrombus formation around the IAB (mean +/- SE; 0 +/- 0.00 heparin versus
1.55 +/- 0.29 no heparin versus 0 +/- 0.00 heparin-bonded; p < 0.005), at the
insertion site (0 +/- 0.00 heparin versus 1.55 +/- 0.29 no heparin versus 0 +/-
0.0 heparin-bonded; p < 0.005), and in the distal femoral artery (0 +/- 0.00
heparin versus 2.00 +/- 0.23 no heparin versus 0 +/- 0.00 heparin-bonded; p <
0.005). CONCLUSIONS: Heparin-bonding of the IAB significantly decreases thrombus
formation in the absence of systemic heparinization.
PMID- 10197669
TI - Multiple arterial conduits without cardiopulmonary bypass: early angiographic
results.
AB - BACKGROUND: Lack of angiographic results and technical difficulty in grafting the
vessels in the lateral and posterior walls have reduced interest in myocardial
revascularization without cardiopulmonary bypass (CPB). We describe our
experience to demonstrate the feasibility of coronary surgical intervention
without CPB in multivessel disease. METHODS: From May 21, 1997, through February
1998, 227 patients underwent revascularization with two or more arterial conduits
as the first operation: 122 without CPB (group A) and 105 with CPB (group B).
Group A included a greater number of high-risk patients. RESULTS: Mean +/- SD
anastomoses per patient were 2.5 +/- 0.6 in group A and 2.8 +/- 0.8 in group B (p
= NS). No patient died in group A, whereas 1 patient (0.9%) died in group B. The
postoperative complication rate was low in both groups, but intensive care unit
and in-hospital stays were shorter in group A than in group B (14.1 +/- 7.1
versus 27.3 +/- 36 hours, p < 0.001, and 4.1 +/- 1.6 versus 5.4 +/- 2.4 days, p <
0.001, respectively [group A versus group B]). Sixty-seven patients in Group A
(54.9%) underwent postoperative angiography 33 +/- 35 days after operation. The
patency rate was 98.9% (98.2% for the marginal branches). CONCLUSIONS: Arterial
revascularization of the coronary arteries without CPB is feasible, with results
similar to those obtained with CPB. The two techniques, in our opinion, are
complementary, not antagonistic.
PMID- 10197670
TI - Complete thromboendarterectomy of the calcified ascending aorta and aortic arch.
AB - BACKGROUND: Arteriosclerotic plaques of the ascending aorta and transverse arch
increase the operative risk of cardiac operations and are strong predictors for
late cerebrovascular events. METHODS: Twenty-two patients, mean age 68 +/- 6
years (range, 55 to 77 years), with grade IV + V plaques of the ascending aorta
and transverse arch underwent coronary artery bypass grafting (n = 21) and aortic
valve replacement (n = 8). Cerebrovascular emboli from unknown sources were found
preoperatively in 8 patients (36%). All were in sinus rhythm. Complete
thromboendarterectomy of the ascending aorta and transverse arch was performed
during hypothermic circulatory arrest. After 21 +/- 12 months (range, 4 to 44
months), magnetic resonance imaging and transthoracic echocardiography of
endarterectomized vessels was performed. RESULTS: There was one perioperative
death (4.5%), one early (4.5%), and one late (4.7%) adverse neurologic event.
Follow-up examinations revealed normal diameters of the endarterectomized aorta.
CONCLUSIONS: For patients with grade IV + V plaques, thromboendarterectomy of the
ascending aorta and transverse arch can be performed with an acceptable surgical
risk and a low recurrence rate for cerebrovascular events. Dilatation of the
endarterectomized aorta was not observed.
PMID- 10197671
TI - Is mediastinitis a preventable complication? A 10-year review.
AB - BACKGROUND: The incidence of mediastinitis after cardiac surgical intervention is
reported to be between 0.15% and 5% and is a major cause of postoperative
morbidity. A number of risk factors have been identified, most of which are not
modifiable. It is our contention that this complication can be reduced to a
minimum by the consistent application of good operative technique and
postoperative management. METHODS: We reviewed the records of all 9,771 patients
who underwent cardiac surgical procedures between 1987 and 1997. All operations
were performed using a common skin preparation, draping, and antibiotic
prophylaxis. Cases of mediastinitis were defined according to Centers for Disease
Control and Prevention criteria and were identified from three sources: medical
records database, hospital infection control, and the Society of Thoracic
Surgeons database. Risk factors were assessed using chi2 and Fisher's exact
tests. RESULTS: Of 24 patients identified as having deep sternal wound infection
(incidence, 0.25%), 2 died (mortality rate, 8.3%), 18 required reoperation (75%),
and only 4 needed pectoral muscle flaps. Statistical analysis revealed only the
presence of chronic obstructive pulmonary disease as a significant risk factor (p
< 0.01). Other factors, including diabetes, renal failure, smoking, sex, age,
reoperation, morbid obesity, and steroid use, were not significant. The use of
internal mammary arteries (single or bilateral) was not associated with
mediastinitis. Postoperative complications, including prolonged ventilation,
inotropic support, and the need for blood products, were not significant risk
factors. The patients who developed mediastinitis were more likely to be
readmitted to the hospital (p < 0.005) and more likely to require reoperation (p
< 0.005). CONCLUSIONS: In a large patient series we found a low incidence of
mediastinitis (0.25%) and an even lower incidence of required reoperation
(0.19%). Except for the use of bone wax and the use of bilateral mammary arteries
in diabetic patients, none of the previously identified risk factors are
modifiable. We believe that with strict adherence to perioperative aseptic
technique, attention to hemostasis, and precise sternal closure, a very low
incidence of mediastinitis can be achieved.
PMID- 10197672
TI - Comparison of long-term clinical results of double versus single internal mammary
artery bypass grafting.
AB - BACKGROUND: The long-term benefits of double versus single internal mammary
artery (IMA) coronary bypass grafting have not yet been established. METHODS: Six
hundred patients were studied retrospectively 10 years after coronary
revascularization using saphenous vein grafts (SVGs) only or single or double IMA
grafts. RESULTS: Patients with double IMA grafts were younger and were more
likely to have diabetes, left main coronary stenosis, and three-vessel coronary
artery disease than patients with SVGs or single IMA grafts. Patients with SVGs
and double IMA grafts had a greater number of diseased coronary vessels and a
greater number of coronary bypass grafts per patient than patients with single
IMA grafts (mean +/- SEM, 2.8 +/- 1.0, 2.8 +/- 0.7, 2.1 +/- 0.8 grafts per
patient, respectively, p < 0.0001). Actuarial survival rates 10 years after
placement of SVGs and single and double IMA grafts averaged 83% +/- 6%, 90% +/-
4%, and 87% +/- 8%, respectively (p = 0.03). Cox regression analysis showed that
diabetes (relative risk, 2.03; 95% confidence interval, 1.55 to 2.66) and chronic
pulmonary obstructive disease (relative risk, 2.20; 95% confidence interval, 1.58
to 3.80) increased, whereas an IMA graft on the left anterior descending coronary
artery significantly decreased, the risk of death after operation (relative risk,
0.45; 95% confidence interval, 0.36 to 0.57) throughout the follow-up period.
CONCLUSIONS: Use of an IMA graft on the left anterior descending coronary artery
improves survival compared with use of an SVG. Although patients with double IMA
grafts had a greater number of poor prognosis risk factors before operation,
their 10-year survival rate was similar to that of patients with a single IMA
graft.
PMID- 10197673
TI - Randomized trial of intermittent antegrade warm blood versus cold crystalloid
cardioplegia.
AB - BACKGROUND: We performed a prospective randomized trial to compare intermittent
antegrade warm blood cardioplegia with intermittent antegrade and retrograde cold
crystalloid cardioplegia. METHODS: Two hundred consecutive patients scheduled for
isolated coronary bypass surgical procedures were randomized into two groups:
Group 1 (n = 92) received cold crystalloid cardioplegia with moderate systemic
hypothermia, group 2 (n = 108) received intermittent antegrade warm blood
cardioplegia with systemic normothermia. Preoperative, intraoperative, and
postoperative data were prospectively collected. RESULTS: For the same median
number of distal anastomoses, cardiopulmonary bypass duration and total ischemic
arrest duration (57.3 +/- 20.5 versus 75 +/- 22.1 minutes, p < 0.001) were
shorter in group 2 than in group 1. Apart from a higher right atrial pressure in
the cold cardioplegia group, no hemodynamic difference was observed. Aspartate
aminotransferase, creatine kinase-MB fraction, and cardiac troponin I levels were
significantly lower in group 2 than in group 1. Outcome variables were not
significantly different. CONCLUSIONS: Intermittent antegrade warm blood
cardioplegia results in less myocardial cell damage than cold crystalloid
cardioplegia, as assessed by the release of cardiac-specific markers. This
beneficial effect has only marginal clinical consequences. Normothermic bypass
has no deleterious effect on end-organ function.
PMID- 10197674
TI - Extracorporeal circulation before and after ultrasonographic evaluation of the
ascending aorta.
AB - BACKGROUND: To further gain insight into atheroembolization mechanisms epiaortic
two-dimensional echocardiographic evaluation before extracorporeal circulation
and after decannulation may be helpful. METHODS: Epiaortic two-dimensional
echocardiography was performed before cannulation and after decannulation in 188
(124 men) patients (mean age, 67.7 years; range, 43 to 86 years) undergoing
operation with extracorporeal circulation for ischemic heart disease during 1996.
RESULTS: After decannulation, a new intimal lesion was recognized in 10 of 188
patients (5.3%): mobile type in 5 patients (3 ending with a stroke [60%], 2
having brain computed tomographic scans compatible with embolism), intimal tear
in 2, and intimal irregularity in 3 patients. Stroke occurred in a significantly
smaller number of patients (2 of 178 [1.1%]; p < 0.001) without new lesions.
CONCLUSIONS: Clamp- or cannula-induced new lesions, especially of mobile type,
are often complicated by postoperative stroke. Aggressive surgical technique
modifications may need to be considered to avoid creating new lesions,
particularly of the mobile type.
PMID- 10197676
TI - Differences in intramuscular vascular connections of human and dog latissimus
dorsi muscles.
AB - BACKGROUND: Distal ischemia and necrosis of the dog latissimus dorsi muscle flap
used in experimental cardiomyoplasty have been reported. However, little
information on the intramuscular vascular anatomy of the dog latissimus dorsi is
available. It is unclear whether there are any anatomic factors relating to the
muscle flap ischemia and necrosis, and whether the dog latissimus dorsi is a
suitable experimental model. METHODS: To study the intramuscular vascular
territories in the dog latissimus dorsi muscle, and to compare the intramuscular
vasculature of the dog with that of the human, 5 fresh dog cadavers and 7 fresh
human cadavers were injected with a mixture of lead oxide, gelatin, and water
(200 mL/kg) through the carotid artery. Both the dog and the human latissimus
dorsi muscles and neurovascular pedicles were dissected and radiographed. The
intramuscular vascular anatomy of the latissimus dorsi muscles was compared.
RESULTS: Radiographs demonstrate clearly that the pattern of latissimus dorsi
intramuscular anastomoses between branches of the thoracodorsal artery and the
perforators of posterior intercostal arteries in the proximal half of the muscle
are different between the dog and the human. In the dog muscle, vascular
connections between the thoracodorsal artery and the posterior intercostal
arteries are formed by reduced-caliber choke arteries, whereas four to six true
anastomoses without a change in caliber between them are found in the human
muscle. The portion of the latissimus dorsi muscle supplied by the dominant
thoracodorsal vascular territory was 25.9% +/- 0.3% in the dog and 23.9% +/- 0.5%
in the human. For further comparison, an extended vascular territory in the
latissimus dorsi muscle was demonstrated, including both the thoracodorsal
territory and the posterior intercostal territories. The area of the extended
vascular territory was 52% +/- 0.5% of the total muscle. CONCLUSIONS: The dog
latissimus dorsi model may not be a perfect predictor of the behavior of the
human latissimus dorsi muscle flap in cardiomyoplasty.
PMID- 10197675
TI - Should the pericardium be closed routinely after heart operations?
AB - BACKGROUND: Repeat coronary artery bypass grafting is more difficult if the right
ventricle is firmly attached to the inner table of the sternum. Closure of the
pericardium at the time of the initial procedure may prevent attachment of the
right ventricle to the sternum. This study attempts to identify the geometric
effects of pericardial closure early after isolated coronary artery bypass
grafting. METHODS: Forty-two patients undergoing elective, isolated coronary
artery bypass grafting were randomized into two groups: 20 patients underwent
closure of the pericardium (Closure group) and the pericardium was left open in
22 patients (Open group). Radiopaque markers were attached to the anterior aspect
of the right ventricular epicardium in both groups. RESULTS: Postoperative chest
roentgenograms revealed that the distance between the epicardial surface and the
posterior table of the sternum was larger in the Closure group compared to the
Open group at 1 week and 3 months postoperatively (p < 0.001). Cardiac index and
stroke work index in the early postoperative period was lower in the Closure
group compared to the Open group (p < 0.001) despite similar filling pressures.
CONCLUSIONS: Pericardial closure may reduce the risk of myocardial injury during
sternotomy for repeat coronary artery bypass grafting by preventing right
ventricular adhesions. However, adverse hemodynamic effects in the early
postoperative period may preclude pericardial closure in patients with impaired
ventricular function.
PMID- 10197677
TI - Assessment of mitral regurgitant jets by three-dimensional color Doppler.
AB - BACKGROUND: Color Doppler echocardiography is a standard technique for assessing
mitral regurgitation before and after mitral valvuloplasty. Mitral valve prolapse
produces complex eccentric jet flows that cannot be visualized and measured by
two-dimensional color Doppler echocardiography. The aim of this study was to
evaluate the clinical impact of three-dimensional color Doppler echocardiography,
a new technique developed at our institution, for assessing mitral regurgitation.
METHODS: Forty-five patients with mitral regurgitation underwent intraoperative
transesophageal echocardiography and three-dimensional Doppler data acquisition.
The grade of mitral regurgitation was assessed by angiography. The jet areas were
calculated by planimetry from conventional color Doppler; the jet volumes were
obtained by three-dimensional Doppler data. RESULTS: New patterns of mitral
regurgitant flows were recognized according to the origin, direction, and spatial
spreading into the left atrium. Conventional jet areas failed to separate the
groups of patients with different degrees of regurgitation, whereas the jet
volumes were able to divide patients with different regurgitation grades. No
significant correlation was found between jet area and angiographic grading (r =
0.63, p = NS). Jet volumes were significantly correlated to angiography (r =
0.89, p < 0.001). CONCLUSIONS: Three-dimensional color Doppler echocardiography
revealed new patterns of regurgitant flow and allowed a more accurate
semiquantitative assessment of complex asymmetrical regurgitant jets.
PMID- 10197678
TI - Minimally invasive direct coronary bypass versus cardiopulmonary technique:
angiographic comparison.
AB - BACKGROUND: Studies comparing minimally invasive direct coronary artery bypass
grafting (MIDCABG) with techniques using cardiopulmonary bypass (CPB) are needed.
METHODS: Sixteen patients underwent single-vessel left internal thoracic artery
left anterior descending (LITA-LAD) MIDCABG through a left anterior thoracotomy,
and 10 underwent multivessel bypass grafting that included a LITA-LAD, using CPB.
Intraoperative completion angiography was performed on all LITA-LAD bypasses, and
graded. One point each was given for: anastomotic patency, pedicle patency,
intercostal obliteration, proper placement into the correct native coronary
artery, and Thrombosis In Myocardial Ischemia grade III flow. RESULTS: There were
no intraoperative deaths or morbidities. LITA takedown averaged 49 +/- 18.6
minutes for MIDCABG and 16 +/- 2.0 minutes for CPB CABG (p < 0.05). LITA length
did not differ between groups (15.3 +/- 1.2 cm for MIDCABG, 14.3 +/- 1.08 cm for
CPB CABG). Ischemic arrest time was significantly less for the CPB group (13.3 +/
8.3 minutes versus 24.5 +/- 9.6 minutes; p < 0.05). Average grade for MIDCABG
LITA-LAD was 4.06 +/- 0.98 points versus 4.77 +/- 0.98 points for CPB LITA-LAD
bypass (p = not significant). CONCLUSIONS: Intraoperative completion angiography
is feasible and, when combined with a grading system, may facilitate the
comparison of MIDCABG with standard techniques.
PMID- 10197679
TI - Surgery for partial atrioventricular septal defect in the adult.
AB - BACKGROUND: We sought to determine the clinical profile, operative results, and
long-term outcome for adult patients undergoing operations for partial
atrioventricular septal defects. METHODS: Between 1976 and 1996, 50 adults (mean
age, 36.6 +/- 13.2 years) underwent surgery for partial atrioventricular septal
defects. Thirty-nine of them underwent primary repair for a substantial left-to
right shunt (> or =1.8), associated with symptoms in 29. The remaining 11
patients had previous atrioventricular septal defect repair in childhood, but
required reoperation as adults for severe left atrioventricular valve
regurgitation (6), subaortic (3) or mitral (1) stenosis, and a residual atrial
shunt (1). RESULTS: No patients died in hospital. Of the 39 patients first
repaired in adulthood, left atrioventricular valve repair was performed in 37,
valve replacement in 1, and no repair in 1. In contrast, left atrioventricular
valve replacement was necessary in 2 of the 6 adults undergoing reoperation for
left atrioventricular valve regurgitation. At 7 years median follow-up, 8
patients have died (2 from noncardiac causes). Of 42 patients alive in 1997, 39
are New York Heart Association class I or II, and 3 were class III (class
improved in 81%). Two patients required left atrioventricular valve replacement
(1 week and 5 years after repair, respectively) for valvar failure. CONCLUSIONS:
Low operative risk and excellent long-term results support repair of partial
atrioventricular septal defect in adults.
PMID- 10197680
TI - A 26-year review of pectus deformity repairs, including simultaneous intracardiac
repair.
AB - BACKGROUND: We reviewed our operative experience and long-term results with
repair of pectus excavatum and carinatum deformities through a vertical midline
approach, including those cases with simultaneous intracardiac repair. METHODS:
From 1972 through 1998, 120 children underwent pectus deformity repair. Operative
technique used a vertical midline incision with subperichondrial resection of
deformed cartilages and an anterior sternal osteotomy. Thirty-five patients had a
temporary metal bar for retrosternal support for 6 months; 85 underwent repair
without a bar. Patients and parents were asked to assess the outcome after pectus
repair as poor, fair, good, or excellent. RESULTS: There were 94 male and 26
female patients (mean age, 8.4 years; range, 3 to 21 years). There were 111 cases
of pectus excavatum and 9 of pectus carinatum. Fourteen children (11.5%) had an
associated congenital heart defect; 9 patients had simultaneous pectus and
intracardiac repair. One patient was referred for emergent open heart repair and
pectus repair after attempted "Nuss" repair resulted in a perforated right
atrium, perforated right ventricle, and partially disrupted tricuspid valve
apparatus. There were no deaths and only one significant complication, which
required a return to the operating room for bleeding. Morbidity was not higher in
patients with simultaneous intracardiac repair. Long-term follow-up was
established in 83% of patients. Results were classified as excellent in 64
patients (64%), good in 25 (25%), fair in 8 (8%), and poor in 3 (3%). Thirty
(86%) of 35 patients with a sternal bar had excellent results versus 34 (52%) of
65 without a bar (p = 0.004); 97% of patients who underwent repair with a sternal
bar classified the result as excellent or good. CONCLUSIONS: Long-term results of
pectus excavatum and carinatum repair through a vertical midline approach are
excellent. Outcome with a temporary sternal bar is superior to outcome without a
bar. Concomitant repair of congenital heart defects and pectus deformity may be
performed successfully without additional morbidity.
PMID- 10197681
TI - Damus-Kaye-Stansel connections in children with previously transected pulmonary
arteries.
AB - BACKGROUND: In patients with a univentricular arteriovenous connection,
transection of the main pulmonary artery may be performed as part of a
bidirectional cavopulmonary shunt or Fontan procedure. The proximal stump of the
pulmonary artery may remain in the systemic circulation. In cases with a
discordant ventriculoarterial connection, subsequent restriction of the
bulboventricular foramen may lead to subaortic stenosis. The subaortic stenosis
can be corrected in some patients by directing the systemic flow through a
combined nonobstructed aortopulmonary outlet, as in the Damus-Kaye-Stansel
connection. Previous closure of the pulmonary artery has been considered by some
investigators to be a relative contraindication to the Damus-Kaye-Stansel
procedure, unless an allograft root can be added to the circuit after excision of
the closed pulmonary stump. METHODS: Three patients with previously transected
pulmonary arteries underwent a modified Damus-Kaye-Stansel connection using the
native pulmonary valve and the proximal pulmonary artery stump. RESULTS: The
native pulmonary valves have functioned well despite thrombus formation in the
proximal stump in 2 patients before Damus conversion. All 3 patients are alive
and well after 108, 19, and 3 months, with competent nonobstructed
ventriculoarterial connections. CONCLUSIONS: If transection and closure of the
pulmonary artery as part of a previous palliation has spared the pulmonary valve,
then the native pulmonary outlet might be used for a safe Damus-Kaye-Stansel
connection.
PMID- 10197682
TI - Effects of chronic pulmonary overcirculation on pulmonary vasomotor tone.
AB - BACKGROUND: A model of shunt-induced pulmonary hypertension was used to study the
effects of pulmonary overcirculation on endothelial nitric oxide synthase (eNOS)
and cytochrome P450-4A (cP450-4A) vasodilatory mechanisms and related hemodynamic
responses. METHODS: An aortopulmonary shunt was constructed in 6-week-old piglets
(n = 7, sham-operated controls n = 8). Hemodynamic measurements were made 4 weeks
later under serial experimental conditions: baseline (fractional concentration of
oxygen, 0.4); inhaled nitric oxide, 25 ppm (INO); hypoxia (fractional
concentration of oxygen, 0.14); hypoxia + INO; N(omega)-nitro-L-arginine
methylester (L-NAME 30 mg/kg intravenously, competitive NOS inhibitor); and L
NAME + INO. Lung protein levels of eNOS and cP450-4A and NOS activity were
compared between groups. RESULTS: Shunted animals had a higher baseline pulmonary
artery pressure (p < 0.05). L-NAME resulted in a greater increase in pulmonary
vascular resistance in shunted animals (150% +/- 26% shunt versus 69% +/- 14%
control; p = 0.01). The INO administered during baseline conditions decreased
pulmonary vascular resistance only in control animals (p < 0.05). Protein levels
of eNOS and NOS activity were similar in both groups; however, cP450-4A protein
levels were decreased in the shunted group (p = 0.02). CONCLUSIONS: The NO
production was preserved in shunted animals but they demonstrated greater
vasodilatory dependence on NO, evidenced by an exaggerated increase in pulmonary
vascular resistance after NOS inhibition. Loss of the cP450-4A vasodilatory
system may be the driving force for NO dependency in the shunted pulmonary
circulation.
PMID- 10197683
TI - Extended end-to-end repair and enlargement of the entire arch in complex
coarctation.
AB - BACKGROUND: Treatment of hypoplasia of the entire arch in coarctation is a
surgical challenge. The current approaches have technical difficulties, high
recurrence rates, and increased morbidity and mortality. METHODS: Over a 14-month
period, a combined extended end-to-end repair with patch enlargement of the
concavity of the entire arch was performed in 6 neonates and 1 infant. Through a
midsternotomy and using cardiopulmonary bypass and hypothermia, extended end-to
end repair was performed initially leaving the proximal anastomosis open. The
enlarging polytetrafluoroethylene patch was then sutured starting at the incised
descending aorta distal to the extended end-to-end repair and continued
retrogradely through the transverse arch to the ascending aorta proximal to the
aortic cannulation site. One neonate had a patent ductus arteriosus and another
had ventricular septal defect closure. One neonate had arterial switch and 3 had
Norwood-type procedures performed with the enlarging patch extended to the
pulmonary artery anastomosis. The remaining infant had arch enlargement performed
after an arterial switch procedure and extended end-to-end repair. RESULTS: All
patients did well and showed no residual gradient up to 1 year follow-up. Two
patients successfully had bidirectional Glenn shunt at 9 months of age, and one
had closure of residual arterial septal defect at 8 months of age. CONCLUSION:
The combined extended end-to-end repair and arch enlargement procedure should
minimize recurrence rates because of a tension-free enlargement of the entire
aortic arch and elimination of the coarctation ridge and ductile tissues.
Combined with the arterial switch and Norwood-type procedures, the approach
results in a large neoaorta.
PMID- 10197684
TI - Surgical resection of intracardiac gastrinoma.
AB - There has been only one previous report of an intracardiac gastrinoma causing
Zollinger-Ellison syndrome. In this communication we describe the successful
surgical resection of a gastrinoma located in the interventricular septum using
cardiopulmonary bypass, blood cardioplegia, and mild hypothermia. Preoperative
evaluation and histologic examination of the resected tumor strongly suggest that
this was a primary intracardiac gastrinoma.
PMID- 10197685
TI - The Freestyle stentless bioprosthesis for prosthetic valve endocarditis.
AB - We report a case of methicillin-resistant Staphylococcus aureus-induced
prosthetic valve endocarditis, which was successfully treated with aortic valve
replacement using the Freestyle stentless bioprosthesis. The total root and
stentless design of this bioprosthesis allows for more radical removal of
infected tissue and easier treatment for annular abscess, while requiring less
prosthetic materials than a conventional prosthesis. This bioprosthesis thus
seems to be a valuable option for active endocarditis.
PMID- 10197686
TI - Acute upper limb ischemia: a complication of coronary artery bypass grafting.
AB - We present the case of a patient with acute upper limb ischemia after radial
artery harvest for coronary artery bypass grafting. This occurred despite
adequate preoperative and intraoperative assessment with the Allen test, hand
held Doppler and radial artery backbleeding. A successful outcome was achieved by
performing brachioradial bypass grafting using reversed cephalic vein.
PMID- 10197687
TI - Carcinoid heart disease and carcinoid syndrome: successful surgical treatment.
AB - Tumor debulking can greatly improve quality of life for patients with malignant
carcinoid syndrome, but hepatic cytoreduction is confounded by carcinoid heart
disease, which can cause postsinusoidal portal hypertension, thereby increasing
the risk of death from hemorrhage during hepatic resection. We describe a patient
with metastatic carcinoid syndrome and carcinoid heart disease who had repair of
his carcinoid heart disease and, after improvement of right-sided heart function,
had successful hepatic debulking of carcinoid metastases.
PMID- 10197688
TI - Aortobronchial fistula after coarctation repair and blunt chest trauma.
AB - A 34-year-old man had development of an aortobronchial fistula 17 years after
patch aortoplasty for correction of aortic coarctation and 5 years after blunt
chest trauma, an unusual combination of predisposing factors. The clinical
presentation, characterized by dysphonia and recurrent hemoptysis, and the
surgical findings suggested the posttraumatic origin of the fistula, which was
successfully managed by aortic resection and graft interposition under simple
aortic cross-clamping, associated with partial pulmonary lobectomy. When
hemoptysis occurs in a patient with a history of an aortic thoracic procedure,
the presence of an aortobronchial fistula should be suspected. Early diagnosis
offers the only possibility of recovery through a lifesaving surgical procedure.
PMID- 10197689
TI - Healing of the intimal dissection of the internal thoracic artery graft.
AB - We report healing of the intimal dissection of an internal thoracic artery graft.
Triple coronary artery bypass grafting was performed using left internal thoracic
artery and saphenous vein grafts. One month after operation, the intimal
dissection of the internal thoracic artery graft was clearly visible by coronary
angiography; however, after 1 year of only medical treatment consisting of
warfarin, ticlopidine, and nitrate, the intimal dissection was undetectable by
coronary angiography.
PMID- 10197690
TI - Drainage of the inferior vena cava to the left atrium.
AB - This report describes a 7-year-old girl with an anomalous connection between the
inferior vena cava and the left atrium documented with intraoperative
transesophageal color-coded Doppler flow echocardiography and angiography. This
rare congenital disorder should be considered in the differential diagnosis in
patients with cyanosis without cardiac murmurs. Operation is the only method for
correction.
PMID- 10197691
TI - Pericardial tamponade: an unusual complication of lobectomy for lung cancer.
AB - A rare case of pericardial tamponade developed in a 69-year-old man after a right
upper lobectomy for lung cancer. This unusual complication presented in the early
postoperative period and was associated with what we believed to be an aberrant
right bronchial artery coming off the intrapericardial portion of the aorta. This
vessel retracted into the pericardial sac where it bled causing a pericardial
tamponade.
PMID- 10197692
TI - Pitfalls of undetected patent foramen ovale in off-pump cases.
AB - We describe pitfalls of a hitherto undetected patent foramen ovale during the
conduct of an off-bypass coronary revascularization. Manipulation of the heart
resulted in right-to-left shunt and severe desaturation requiring institution of
cardiopulmonary bypass to close the patent foramen ovale and complete the
revascularization.
PMID- 10197693
TI - Metachronous cancers or late recurrences after resection of stage I lung cancer.
AB - In 2 patients with stage I lung cancer, tumors recurred at their resection lines
10 years after the original surgical resections. These cases suggest that the
prognosis of late cancer occurrences after resected primary lung malignancies
might be related to the interval of time between primary and subsequent cancers
rather than to their categorization as recurrent or metachronous cancers.
PMID- 10197694
TI - Bronchial-atrial fistula after lung transplant resulting in fatal air embolism.
AB - We describe a rare case of fatal air embolism in a patient in whom a left atrial
bronchial fistula developed 1 month after single lung transplant. The cause was a
combination of mediastinal infection and bronchial necrosis.
PMID- 10197695
TI - Progressive pulmonary autograft root dilatation and failure after Ross procedure.
AB - We present a case of progressive pulmonary autograft root dilatation and
subsequent failure after a Ross procedure. The explanted autograft vessel wall
revealed striking histologic findings indicative of chronic media rupture.
Examination of another explanted pulmonary autograft root showed similar
histologic changes, suggesting a common phenomenon in pulmonary autograft roots.
It may be the cause of progressive root dilatation as observed after Ross
operations.
PMID- 10197696
TI - Treatment of infected left ventricular assist device using antibiotic-impregnated
beads.
AB - There is no well-established therapy for treating infections of heart-assist or
artificial heart devices, a serious problem with life-threatening consequences.
We used a promising new approach in which antibiotic-impregnated
polymethylmethacrylate beads were placed around an implanted left ventricular
assist device to control an external blood pump infection in a bridge-to
transplant patient. In this case report, we describe the potential of
antimicrobial-impregnated polymethylmethacrylate beads for in situ control of
infections involving external surfaces of cardiovascular devices.
PMID- 10197697
TI - Cardiac pheochromocytoma: resection after diagnosis by 111-indium octreotide
scan.
AB - Cardiac pheochromocytoma is an exceedingly rare and unusual clinical entity. Only
37 previous surgically treated adult patients were found in review of the
surgical literature. We report the case of a 13-year-old boy who had a cardiac
pheochromocytoma that was localized by the 111-indium diethylenetriamine
pentaacetic acid octreotide scintigraphy scan and confirmed by magnetic resonance
imaging after computed tomographic and B1-iodine-metaiodobenzylguanidine scans
had failed. At operation, a 6-cm pheochromocytoma of the left atrium was found
and successfully resected with reconstruction of the left atrium using autologous
pericardium.
PMID- 10197698
TI - High origin of the right coronary artery with congenital heart disease.
AB - We encountered a case of anomalous high origin of the right coronary artery
associated with ventricular septal defect and patent ductus arteriosus. The right
coronary artery originated from the distal part of the ascending aorta resulting
in unsuccessful induction of cardiac arrest by cardioplegia. We describe this
rare case with anomalous origin of the right coronary artery.
PMID- 10197699
TI - Extended Ross procedure for aortic valve stenosis and ascending aortic and arch
hypoplasia.
PMID- 10197701
TI - Videoscopic harvest of the inferior epigastric artery.
AB - The inferior epigastric artery has been found to be a useful conduit for
performing arterial coronary revascularization. The present report describes a
minimally invasive port access technique for harvesting the inferior epigastric
artery.
PMID- 10197700
TI - Simplified technique for implantation of a left ventricular assist system after
previous cardiac operations.
PMID- 10197702
TI - Protective wrapping of the internal thoracic artery.
AB - Injury of a patent internal thoracic artery bypass graft in a patient during
cardiac reoperation could have catastrophic results. In selected patients who
have primary coronary artery bypass grafting using the internal thoracic artery,
we wrap the artery pedicle with an expanded polytetrafluoroethylene membrane to
facilitate identification and to protect it during reoperation. No occlusions or
other complications related to use of the membrane have occurred.
PMID- 10197703
TI - Suprahepatic inferior vena cava cannulation.
AB - Inadequate venous drainage may represent a major problem in operations on the
descending thoracic aorta performed with the aid of cardiopulmonary bypass. We
herein describe an alternative technique of venous cannulation, which allows
steady performances and high pump flows.
PMID- 10197704
TI - Minimally invasive vein harvest: new techniques with old tools.
AB - Greater saphenous vein harvest has been the focus of increasing applications of
endoscopic techniques aimed at reducing wound complication, increasing patient
comfort, and providing more acceptable cosmetic results. A retired, reusable,
lighted retractor used for breast surgery was adapted using minimally invasive
and bridge techniques resulting in decreased incisions, gentle vein handling,
decreased harvest to closure time, and better wound healing compared with open
techniques.
PMID- 10197705
TI - Pericardial patch for atrial septal defect closure.
AB - Pericardium is an eminently suitable material for the closure of atrial septal
defects. However, when it is not treated with glutaraldehyde, it is difficult to
handle because of curling in of the edges. A technique is described by which
pericardium can be used to close atrial septal defects with minimal handling and
assistance, and without chemical pretreatment.
PMID- 10197706
TI - Ablation of persistent air leaks after thoracic procedures with fibrin sealant.
AB - Prolonged air leak after thoracic procedures was successfully treated in 11 of 12
patients under local anesthesia using video thoracoscopic instillation of fibrin
sealant over the site of the leak. No related complications occurred. This method
should be considered an effective option for the treatment of persistent
pulmonary air leaks.
PMID- 10197707
TI - Early Islamic physicians and thorax.
AB - Modern anatomic knowledge has developed throughout centuries with transfer of
knowledge from generations to generations. Ibn-i Sina (980-1037), Razi (850-923),
Davud El-Antaki (?-1008), Ali ibn Abbas (?-982), Ahmed bin Mansur (14th century),
Semseddin-i Itaki (1570-1640), and Ibn-i Nafis (1210-1288) were Islamic
physicians who all contributed to the understanding of anatomy. They benefited
from Greek and Roman pioneers, as well as from each other. To show the situation
of thoracic anatomy in early Islamic physicians, we analyzed two original
manuscripts in the Suleymaniye Library and some contemporary texts. There were
original drawings of the trachea, lung, and vascular system in Semseddin-i
Itaki's and Ahmed bin Mansur's anatomy texts. Ibn-i Nafis's writings revealed
that he was the first person to describe the pulmonary circulation. Also Ali ibn
Abbas wrote that the pulmonary artery wall had two layers and these layers may
have a role in constriction and relaxation of this vessel. He also stated that
pulmonary veins branched together with the bronchial tree. Ahmed bin Mansur, Ali
ibn Abbas, and Ibn-i Nafis each wrote that the heart has two cavities. They also
added that the wall of the septum is very thick and there are no passages in
between. These show that Islamic physicians had important contributions to
thoracic anatomy and physiology. European physicians benefited from these
contributions till the end of the 16th century.
PMID- 10197708
TI - Mediastinal parathyroid cysts revisited.
AB - BACKGROUND: A case of a functioning mediastinal cyst is presented. METHODS: A
comprehensive review of the literature found 93 patients in whom a parathyroid
cyst or cysts extended into, or was completely contained within, the mediastinum.
Including our patient, there were 46 men and 45 women, and the gender was not
recorded in three. RESULTS: The cysts were located in the anterosuperior region
in 56 patients, in the middle region of the mediastinum in 26, and in the
anterior, prevascular region in 12. Thirty-nine patients had functioning cysts
associated with hyperparathyroidism of varying severity; seven patients presented
with a hypercalcemic crisis. Local symptomatology consisted of a neck mass,
respiratory distress, and occasional dysphagia or chest pain. Recurrent laryngeal
nerve paresis was present in nine patients, and innominate vein compression or
thrombosis was present in two. The cysts in all but four patients were treated by
open surgical excision; two were treated by thoracoscopy, and two patients only
had fine-needle aspiration of the cyst. The cyst was excised via a cervical
approach in 67 patients and by a thoracotomy or median sternotomy or a variation
thereof in 23. There was no operative mortality and morbidity was minimal.
CONCLUSION: Surgical resection was successful in all and remains the treatment of
choice for mediastinal parathyroid cysts.
PMID- 10197709
TI - As originally published in 1992: Anterior mediastinal tracheostomy with and
without cervical exenteration. Updated in 1998.
AB - Anterior mediastinal tracheostomy (AMT) facilitates resection of stomal
recurrences after laryngectomy for carcinoma and tumors involving the
cervicothoracic trachea and esophagus. Erosion of the innominate artery has been
reported as a frequent major complication of AMT, and routine prophylactic
division of the innominate artery with AMT has even been advised. Forty-four
patients underwent AMT, 10 as an isolated procedure (for stomal recurrence,
laryngeal carcinoma, or benign stenosis after laryngectomy) and 34 with
concomitant cervical exenteration (laryngopharyngoesophagectomy) for laryngeal,
thyroid, or cervicothoracic esophageal malignancies. Transposition of the
remaining tracheal stump beneath and to the right of the innominate artery to
eliminate tension on the vessel was carried out in 14 patients (32%).
Postoperatively, anastomotic leaks complicated nine of 31 pharyngogastric
anastomoses. Iatrogenic hypoparathyroidism occurred in 10 patients. All six
hospital deaths (14%) occurred in patients undergoing AMT with cervical
exenteration, not isolated AMT. There was only one instance of innominate artery
erosion. Survival was related to the pathology for which AMT was performed.
Anterior mediastinal tracheostomy is a valuable adjunct in the treatment of
select patients with malignancies of the cervicothoracic trachea and esophagus,
and with attention to operative detail, innominate artery erosion should rarely,
if ever, complicate the operation. Prophylactic division of the innominate artery
with AMT is unnecessary.
PMID- 10197710
TI - Cardiac transplantation with single-lung pulmonary hypertension.
PMID- 10197711
TI - Outcome after transcervical thymectomy.
PMID- 10197712
TI - Surgical management of the ruptured aortic arch.
PMID- 10197713
TI - Bulldog with spikes: clamp for coronary artery operations.
PMID- 10197714
TI - Deep wound infection following minithoracotomy for coronary bypass grafting.
PMID- 10197715
TI - Tumor necrosis factor-alpha and cardiac surgical procedures: still more questions
than answers.
PMID- 10197716
TI - Are we implanting half-valves? The role of sinus wall compliance in aortic valve
function.
PMID- 10197717
TI - Pericardial lift facilitates central cannulation in left anteroaxillary
thoracotomy.
PMID- 10197718
TI - Congenital coronary-to-pulmonary artery fistulas: 22 months after repair.
PMID- 10197719
TI - A surgical method for selecting appropriate size of graft in aortic root
remodeling.
PMID- 10197720
TI - Combined therapies for composite graft infection after Bentall's procedure.
PMID- 10197721
TI - Minimally invasive cardiac surgery.
PMID- 10197722
TI - Optimizing valve exposure with minimally invasive operations.
PMID- 10197723
TI - Longevity, genes, and aging: a view provided by a genetic model system.
AB - The genetic analysis of aging in the yeast Saccharomyces cerevisiae has revealed
the importance of metabolic capacity, resistance to stress, integrity of gene
regulation, and genetic stability for longevity. A balance between these life
maintenance processes is sustained by the RAS2 gene, which channels cellular
resources among them. This gene cooperates with mitochondria and PHB1 in
metabolic adjustments important for longevity. It also modulates stress
responses. Transcriptional silencing of heterochromatic regions of the genome is
lost during aging, suggesting that gene dysregulation accompanies the aging
process. There is evidence that this age change plays a causal role. Aging
possesses features of a nonlinear process, and it is likely that application of
nonlinear system methodology to aging will be productive.
PMID- 10197724
TI - Age-related changes of signal transduction in T cells.
PMID- 10197725
TI - Reactive oxygen species and biological aging: a mechanistic approach.
AB - The experimental evidence for an age-dependent increased generation of reactive
oxygen species and a progressive accumulation of oxidized biomolecules is
growing. However, despite such facts there is no detailed mechanistic information
on how the higher availability of reactive oxygen species translates into the
accumulation of oxidized biomolecules. For example, open questions are which
reactive oxygen species are responsible for what types of oxidation products in
vivo, under what specific reaction conditions can we expect which reaction
products, and why specifically are modified biomolecules eliminated whereas
others accumulate? Mitochondria appear to serve as the major source for reactive
oxygen species in aging tissue. Genetic experiments have demonstrated an effect
of Cu,ZnSOD on life span and in the prevention of age-related oxidative damage,
suggesting that extramitochondrial superoxide promotes biological aging. However,
as superoxide does not easily cross membranes, potential chemical pathways that
convert mitochondrial reactive oxygen species into superoxide outside the
mitochondria are displayed. The chemical reactivity of individual reactive oxygen
species with the amino acid side chain of methionine is surveyed to obtain
mechanistic details on the oxidation pathways potentially leading to the age
dependent methionine oxidation of the protein calmodulin in vivo. It will evolve
that the in vivo accumulation of oxidized calmodulin cannot be the result of the
reaction of an individual reactive oxygen species with calmodulin in homogenous
solution alone. Complexation of calmodulin to calmodulin-binding proteins and
protein turnover are additional parameters likely contributing to the
accumulation of specifically modified calmodulin.
PMID- 10197726
TI - Further evidence for the rejuvenating effects of the dipeptide L-carnosine on
cultured human diploid fibroblasts.
AB - We have confirmed and extended previous results on the beneficial effects of L
carnosine on growth, morphology, and longevity of cultured human fibroblasts,
strains MRC-5 and HFF-1. We have shown that late-passage HFF-1 cells retain a
juvenile appearance in medium containing 50 mM carnosine, and revert to a
senescent phenotype when carnosine is removed. Switching cells between medium
with and without carnosine also switches their phenotype from senescent to
juvenile, and the reverse. The exact calculation of fibroblast lifespans in
population doublings (PDs) depends on the proportion of inoculated cells that
attach to their substrate and the final yield of cells in each subculture. We
have shown that carnosine does not affect cell attachment, but does increase
longevity in PDs. However, the plating efficiency of MRC-5 cells seeded at low
density is strongly increased in young and senescent cells by carnosine, as shown
by the growth of individual colonies. We have also demonstrated that very late
passage MRC-5 cells (with weekly change of medium without subculture) remain
attached to their substrate much longer in medium containing carnosine in
comparison to control cultures, and also retain a much more normal phenotype.
Carnosine is a naturally occurring dipeptide present at high concentration in a
range of human tissues. We suggest it has an important role in cellular
homeostasis and maintenance.
PMID- 10197727
TI - Aging and red blood cell membrane: a study of centenarians.
AB - Successful aging, characterized by little or no loss in physiological functions,
should be the usual aging process in centenarians. It is known that well
preserved physiological functions depend on the proper functioning of cell
systems. In this article we focus on cell membrane integrity and study the red
blood cell membrane to evaluate the effect of physiological aging in
centenarians. Fifteen healthy, self-sufficient centenarians, mean age 103 years,
were examined by assessing hemocytometric values and some relevant
characteristics of the erythrocyte membrane, i.e., the cholesterol/phospholipid
molar ratio, the distribution of phospholipid classes and their fatty acid
composition, the integral and skeletal protein profiles. The centenarians showed
a significant decrease in the red blood cell count (p < 0.0002), hemoglobin (p <
0.0002), and hematocrit (p < 0.0005). The red blood cell membrane showed a
significantly increased cholesterol/phospholipid molar ratio (p < 0.01), with a
concomitant increase in polyunsaturated fatty acids in phosphatidylcholine (p <
0.001) and, to a lesser extent, in phosphatidylethanolamine. The electrophoretic
pattern of membrane proteins was qualitatively normal compared to controls but
the densitometric analysis showed a significant increase in the integral protein
band 4.2 (p < 0.05) and in the skeletal protein actin (p < 0.001). Extreme
longevity seems to be associated with a substantial integrity of the erythrocyte
membrane. Moreover, the evident increase in polyunsaturated fatty acids and in
actin are likely to improve the membrane fluidity and to strengthen the membrane
structure.
PMID- 10197728
TI - T-lymphocyte long-term cultures have a constant histone variant pattern during
aging.
AB - Human peripheral long-term T-lymphocyte cell cultures show some characteristics
similar to those of fibroblast cell lines, the latter of which have been used as
in vitro systems for cellular aging studies for many years. Both show a limited
in vitro life span, as well as a progressive prolongation of their cell cycle
with increasing age. However, whereas T-cell cultures die from apoptosis at the
end of their proliferative capacity, fibroblasts can be maintained for long
periods of time in stationary cultures as postmitotic senescent cells. Previous
studies analyzing the histone variant pattern of a human lung embryonic
fibroblast cell line have shown that this pattern changes as a function of
cumulative population doublings in a manner not unlike that found in terminally
differentiating systems. In the present study the histone variant composition of
long-term T-cell cultures was analyzed as a function of population doublings and
compared to a human diploid fibroblast system. The results from this study
provide a distinction at the molecular level among these two in vitro aging model
systems, because it was found that long-term T-cell cultures show a constant
histone variant constitution throughout their in vitro life, dissimilar to
previous findings using the fibroblast cell system.
PMID- 10197729
TI - Finite lifespans of T cell clones derived from CD34+ human haematopoietic stem
cells in vitro.
AB - Several studies have documented finite lifespans of at least the vast majority of
cultured human T cell lines and clones. However, there is a great deal of
variation among the different preparations, ranging from < 25 PD up to > 100 PD.
The cultured T cells in all these studies originated from mature T cells isolated
from peripheral blood of adult donors. It was, therefore, impossible to assess
the contribution of differences in in vivo age to the subsequent differences
between clones in in vitro aging. In an attempt to circumvent this difficulty, we
have developed a culture system that supports the differentiation of highly
purified human CD34+ cells into CD3+ T cells in vitro. This features the use of a
serum-free medium supplemented with the cytokines flt-3 ligand, IL 3, stem cell
factor (c-kit ligand) and IL 2, together with IL 7 or oncostatin M (OM). In this
way it is possible to perform "longitudinal" studies on T cells derived de novo
in vitro. We show here that T cell clones derived under these circumstances also
manifest variable finite life expectancies, for which the only uncontrolled
(nonstochastic) effects of aging must already have occurred at the stem cell
level.
PMID- 10197730
TI - CD69, CD25, and HLA-DR activation antigen expression on CD3+ lymphocytes and
relationship to serum TNF-alpha, IFN-gamma, and sIL-2R levels in aging.
AB - Aging is associated with changes in lymphocyte subsets and unexplained HLA-DR
upregulation on T-lymphocytes. We further investigated this activation, by
measuring early (CD69), middle (CD25), and late (HLA-DR) T-lymphocyte activation
markers on CD3+ lymphocytes, across subjects (20-100 years) together with serum
tumor necrosis factor (TNF-alpha), interferon-gamma (IFN-gamma), and soluble
interleukin-2 receptor (sIL-2R). HLA-DR was present as a CD3+ HLA-DR+ subset that
constituted 8% of total lymphocytes, increased twofold with age and included
CD4+, CD8+, and CD45RA+ phenotypes. HLA-DR was also expressed on a CD8+ CD57+
subset. The CD3+ CD25+ subset constituted 13% of lymphocytes, fell with age but
was weakly associated with the CD3+ HLA-DR+ subset especially in older subjects.
A small 3-5% CD3+ CD69+ subsets showed no age effect. Serum sIL-2R, TNF-alpha,
but not IFN-gamma, were associated with CD3+ HLA-DR+ lymphocytes, TNF-alpha with
CD8+ CD57+ count and sIL-2R and IFN-gamma with the CD3+ CD25+/CD3+ CD4+ ratio.
The study confirms age-related upregulation of HLA-DR on CD3+ lymphocytes, shows
some evidence for associated upregulation of CD25 on CD3+ cells in older
subjects, and links serum TNF-alpha, IFN-gamma, and sIL2-R to T-lymphocyte
activation.
PMID- 10197732
TI - Dose-dependent antibody response to influenza H1N1 vaccine component in elderly
nursing home patients.
AB - The effects of an increased antigen dose on HI, IgG, IgA, and IgM antibody
responses to influenza A/Taiwan/1/86 (H1N1) were investigated in 92 elderly
nursing-home residents (mean age 81 years) and 104 young subjects (mean age 20
years). At a standard 10-microg dose, HI and IgG titer rises were lower in the
elderly. HI titers did not improve at higher vaccine dosages. By contrast,
influenza-specific IgG and IgA antibody responses were dose dependent in elderly
subjects, but not in young. In the young subjects, IgM antibody responses were
dose dependent. The improved antibody responses in the elderly as observed in IgG
and IgA were not reflected in the HI response. Therefore, the evaluation of
antibody production by HI only may lead to an underestimate of the immune
response in elderly people.
PMID- 10197731
TI - Studies into the effect of tyrosine phosphatase inhibitor phenylarsine oxide on
NFkappaB activation in T lymphocytes during aging: evidence for altered IkappaB
alpha phosphorylation and degradation.
AB - Nuclear Factor kappa B (NFkappaB) is a critical regulator of several genes
involved in immune and inflammatory responses. Treatment of T cells with a
variety of stimuli, including TNF-alpha, leads to the translocation of the active
p65-50 heterodimer to the nucleus, albeit at a lower level in T cells from the
elderly. We demonstrate here that pretreatment with PAO results in the inhibition
of NFkappaB induction in TNF-alpha treated T cells, suggesting a role for PAO
sensitive phosphatase in the activation of the NFkappaB via this pathway in human
T cells. Furthermore, it demonstrates that aging does not influence the
sensitivity of this phosphatase. Treatment with DMP prior to treatment with PAO
and TNF abolishes the inhibition induced by PAO, in T cells from both young and
old donors, alike. Finally, we demonstrate that a failure to degrade IkappaB
alpha in cytosols of TNF-treated T cells pretreated with PAO is due to its
interference with the phosphorylation of IkappaB-alpha and not due to its
inhibitory effect on proteasomal degradation. These data collectively suggest
that PAO interferes with the phosphorylation and the regulated degradation of
IkappaB-alpha, induced by TNF, without affecting the chymotryptic activity of the
proteasome, independent of age.
PMID- 10197733
TI - Neurotransmitters, peptides, and neural cell adhesion molecules in the cortices
of normal elderly humans and Alzheimer patients: a comparison.
AB - Immunocytochemical techniques was used to compare the proportion of neurons
expressing various neurotransmitters (tyrosine hydroxylase, choline
acetyltransferase and gamma-aminobutyric acid), neuropeptides (Leu-enkephalin and
substance P) and neural cell adhesion molecules (NCAM) in the hippocampus,
frontal (area 10) and occipital (area 17) cortices of neurologically normal
elderly humans to that of age-matched Alzheimer disease (AD) patients. There was
no difference in the proportion of GABAergic and cholinergic cells between the
normal and AD groups in all three brain regions studied. However, the
catecholaminergic cells in the frontal cortex of the AD patients revealed a
significant decrease. The catecholaminergic cells present in the cortex were both
neurons and astrocytes, as revealed by a double immunostaining of tyrosine
hydroxylase and glial fibrillary acid protein (GFAP). Furthermore, the difference
in the proportion of cells expressing Substance P and Leu-enkephalin was minimal
between the two groups studied. Although there was little difference in the
levels of NCAM in the occipital cortex and hippocampus of the two groups, there
were significantly fewer positive NCAM neurons in the frontal cortex of AD than
normal aging individuals.
PMID- 10197734
TI - Voluntary nystagmus associated with accommodation spasms.
AB - BACKGROUND: Voluntary nystagmus has been recognized as a pendular, rapid,
conjugate, primarily horizontal, benign eye movement initiated and maintained by
voluntary effort. CASE: A 10-year-old Japanese girl presented with voluntary
nystagmus associated with accommodation spasms. Her chief complaints,
intermittent blurred vision, headache, and soreness of the eyes, were thought to
be related to the voluntary nystagmus and accommodation spasms. FINDINGS: The
waveform of the nystagmus appeared pendular, the frequency was 13-15 Hz, and the
amplitude was 3-5 degrees. Scanning laser ophthalmoscopic video images clearly
demonstrated vertical and torsional components in addition to the horizontal eye
movements. Her refraction was unstable, varying between -0.5 diopters (D) and
5.5 D, and the recording of the accommodometer increased to -12.0 D when
nystagmus was initiated. CONCLUSIONS: This may be a unique form of voluntary
nystagmus that consists of horizontal, vertical, and rotational components
associated with accommodation spasms. Observation of this patient continues,
without any further treatment or examination.
PMID- 10197735
TI - Measuring short-wavelength-sensitive cone discrimination thresholds using
pseudoisochromatic figures displayed on a color monitor.
AB - PURPOSE: To simplify the testing of short-wavelength-sensitive (SWS) cone
function in the clinic. METHODS: SWS-cone discrimination thresholds were measured
along the tritan axis using pseudoisochromatic figures displayed on a color
monitor. A circular 6 degrees field, containing spatially discrete patches of
varying sizes and luminances, was presented on a background. A subset of patches
formed the target patch in the shape of a C. Eight subjects with normal color
vision reported the direction of the gap in the C using a cursor controlled by a
joystick. DATA: were expressed in units of SWS-cone trolands. RESULTS: SWS-cone
discrimination threshold increased slowly as the SWS-cone trolands of the
starting chromaticity increased. The dependence of the threshold on the SWS-cone
activation level was similar to literature reports of chromatic discrimination
measured with conventional paradigms. CONCLUSIONS: The advantages of this method:
(a) It is a simple intuitive task for patients. (b) The paradigm can be
implemented with an 8-bit/gun color monitor. (c) The test avoids the need to
define equiluminance for the individual patient before the color test is
administered. This method can provide a useful technique for measuring SWS-cone
function in a clinical population.
PMID- 10197736
TI - Studies on the function of the checkerboard pattern stimulator: analysis of
ocular positions during stimulation.
AB - PURPOSE: To analyze the effectiveness of the checkerboard pattern stimulator
(CPS) in facilitating stereopsis in patients with acquired esotropia. METHODS:
Fourteen patients were treated with checkerboard pattern stimulation following
surgical correction of the ocular alignment. In order to determine the cause of
the difference in the effectiveness of CPS on exotropes and esotropes, a separate
study was carried out on 15 subjects: 5 orthophores, 5 exophores, and 5
esophores. RESULTS: Eight of the 14 patients achieved stereopsis; the remaining 6
cases did not show marked improvement in stereoacuity. The CPS was more effective
on exotropes, as reported previously, than on esotropes (P = 0.047, chi2 test).
By recording the ocular positions of the 15 subjects in the separate study, we
found a tendency toward exodeviation in the orthophoric and exophoric subjects
but not in esophoric subjects. CONCLUSIONS: Our results suggest that CPS develops
sensory fusion by providing an identical pattern simultaneously to the foveas of
both eyes and has no effect on convergence training and motor fusion.
PMID- 10197737
TI - A new system to supply carbon dioxide safely to glaucoma patients.
AB - PURPOSE: To develop a new system for safely supplying carbon dioxide (CO2) to
open-angle glaucoma patients. METHODS: The orbital hemodynamics of 7 glaucoma
patients were determined by color Doppler imaging under baseline conditions and
during CO2 supplementation sufficient to increase the end-tidal CO2 partial
pressure by 10%. Systemic conditions, including oxygen saturation and blood
pressure, were monitored throughout the CO2 inhalation. RESULTS: Our results
demonstrate that this new system enables us to supply CO2 in a safe, controlled
manner to glaucoma patients. CONCLUSIONS: This new system will be useful for
investigating the effects of vasodilation by CO2 on orbital blood flow.
PMID- 10197738
TI - Pupillary functions after cataract surgery using flexible iris retractor in
patients with small pupil.
AB - PURPOSE: To quantitatively assess pupillary functions after small pupil cataract
surgery using the flexible iris retractor. METHODS: Subjects were 11 patients (12
eyes) with small pupils who underwent phacoemulsification and intraocular lens
implantation. Pupils were enlarged using the flexible iris retractor
intraoperatively, and postoperative iriscorder data were compared with the data
of 20 normal controls who underwent standard phacoemulsification and intraocular
lens implantation. RESULTS: Although pupillary area before light stimulus did not
differ between the groups, contraction rate after light stimulus was
significantly lower in the small pupil group than in the normal controls. The
velocity of contraction and dilation was also significantly slower in the small
pupil group. Wider pupillary stretching during surgery resulted in deteriorated
pupillary functions after surgery. Eyes of patients on long-term miotic therapy
with pilocarpine showed poorer pupillary reaction postoperatively. CONCLUSION:
Inappropriate use of the flexible iris retractor causes an atonic, chronically
enlarged postoperative pupil. To avoid postoperative pupillary complications,
miotic pupils should not be stretched to larger than a 5.0 x 5.0 mm square.
PMID- 10197739
TI - Fluorescein and indocyanine green videoangiography of choroidal melanomas.
AB - PURPOSE: This study was performed to determine what role indocyanine green video
angiography might play in the evaluation of choroidal melanomas, and to compare
this role with that of fluorescein angiography. METHODS: Six patients with
posterior segment uveal melanoma underwent digital fluorescein and indocyanine
green videoangiography. All patients were women and their mean age was 50.7
years. RESULTS: In all eyes with melanoma, fluorescein angiography revealed
irregular hyperfluorescence in the early phase and staining of the tumor in the
late phase. A double circulation pattern was obvious in 1 eye with a mushroom
shaped melanoma. The patterns of indocyanine green videoangiography varied,
depending on the degree of tumor pigmentation, thickness, and vascularity. Early
frames of indocyanine green video angiography demonstrated hypofluorescence in
all eyes, and the intrinsic choroidal vasculature was obvious in 3 eyes. In the
late phase of indocyanine green videoangiograms, different patterns
(hyperfluorescence, three-ring pattern) were observed. CONCLUSION: Indocyanine
green videoangiography may be a useful adjunct to fluorescein angiography in the
evaluation of choroidal melanomas.
PMID- 10197740
TI - Ocular ischemic syndrome in diabetic patients.
AB - PURPOSE: Diabetes mellitus aggravates carotid occlusive disease, that can
manifest as ocular ischemic syndrome (OIS). Ocular manifestations and visual
prognosis of OIS in diabetic patients were retrospectively analyzed. METHODS:
Twenty-three consecutive diabetic patients with OIS were divided into two groups
according to the presence of iris neovascularization, and the clinical features
were reviewed. RESULTS: In the first group, 14 eyes of 12 diabetic patients (11
men and 1 woman) had no iris neovascularization. Two patients had bilateral OIS.
The ages in this group ranged from 50-75 years. Four eyes with optic atrophy or
ischemic optic neuropathy had severe visual loss. Six eyes with hypoperfusion
retinopathy or retinal vein obstruction and 2 eyes with cataract had mild visual
loss. Each eye with amaurosis fugax or retinal neovascularization had no visual
deterioration. Asymmetrical retinopathy was observed in 2 patients. Carotid
surgery stabilized and resolved amaurosis fugax and hypoperfusion retinopathy. In
the second group, 11 eyes of 11 patients had iris neovascularization. The
patients were all male and their ages ranged from 53-77 years. All eyes with iris
neovascularization had severe visual deterioration. In 5 patients, asymmetrical
ocular manifestation was observed. Carotid reconstruction surgery and
ophthalmological treatment were not successful for recovering a satisfactory
visual outcome in OIS. CONCLUSION: The features of OIS in diabetic patients mimic
diabetic retinopathy and manifest with asymmetrical ocular findings. Iris
neovascularization is an indicator of poor visual prognosis. It is essential to
recognize the early stages of OIS associated with diabetes mellitus.
PMID- 10197741
TI - Topographical analysis of motion-triggered visual-evoked potentials in man.
AB - PURPOSE: The middle temporal (MT) area of the cortex of the monkey is involved in
visual motion analysis. Previous studies using brain-imaging techniques have
shown that the area around the anterior occipital cortex in man is homologous to
the area MT of the monkey. In this study, we investigated the cortical components
of motion-triggered visual evoked potentials and their topography in the visual
cortex of man. METHODS: Visual evoked potentials to the onset of a visual motion
stimulus (m-VEPs) were recorded from 5 normal subjects aged 25 to 34 years. A
random dot pattern was used as the stimulus for the m-VEPs. The dots moved
horizontally to the right and then to the left alternately for 500 milliseconds
with interstimulus intervals of 1500 milliseconds. The speed of motion was varied
in five steps from 5-25 degrees/s. Fifteen electrodes were placed on the occiput
around O(z) at 5-cm intervals. Color contour maps showing the distribution of
voltage over the 15 electrodes at latencies ranging from 0-200 milliseconds with
a 20-millisecond interval were made for each subject. These were coregistered
with three-dimensional magnetic resonance images of the same brain to specify the
topography of the main components of the m-VEPs in relation to the sulcal and
gyral pattern of the visual cortex. RESULTS: We consistently observed a positive
wave with a peak latency of about 100 milliseconds (P100) and a negative wave
with a peak latency of about 150 milliseconds (N150) for all subjects.
Topographical analysis showed that P100 was dominant in a relatively wide area
caudal to O(z), whereas N150 was dominant in a relatively small area posterior to
the right anterior occipital sulcus, which included the area corresponding to the
area MT in man. CONCLUSIONS: These findings suggest that N150 represents the
activity of the area MT in the human visual cortex related to motion perception.
PMID- 10197742
TI - Kinetics of foveal cone photopigment in myopia without chorioretinal
degeneration.
AB - PURPOSE: To study the early changes in the outer retina of myopic eyes, we
performed fundus reflection foveal cone densitometry in 45 subjects with normal
visual acuity and no chorioretinal degeneration (ages: 18-47 years, refraction;
+2.00-(-14.50) diopters). METHODS: After full bleaching, the density of the
photopigment was measured for 7 minutes by using a test spot, 562 nm in
wavelength and 1 degrees in diameter, focused on the fovea. We calculated the
density difference (DD) and the time constant (TC) of photopigment regeneration.
RESULTS: Although we found no correlation between the DD and the refractive
error, there was a significant increase in TC as the refractive error increased
(r = 0.50, P < 0.01). CONCLUSIONS: These findings indicated that the kinetics of
cone pigments become abnormal preceding the loss of cone cells or chorioretinal
degeneration in high myopia.
PMID- 10197743
TI - Ophthalmic findings in GAPO syndrome.
AB - BACKGROUND: The main manifestations of GAPO syndrome are growth retardation (G),
alopecia (A), pseudoanodontia (P), and optic atrophy (O). CASES: This syndrome
has been described in 21 patients from 16 different families. Four cases are from
Turkey and have been presented by Sayli and Gul. The purpose of our study is to
document the cases from Turkey and discuss the ophthalmological and neuro
ophthalmolgical findings of these and other reported GAPO cases. OBSERVATIONS:
All patients in the literature and our 4 cases have severe growth retardation
with delayed bone age in infancy, characteristic facial appearance (high and
bossed forehead, midface hypoplasia), alopecia or severe hypotrichosis, and
pseudoanodontia. Optic atrophy was present in 1 of our cases and in 5 previous
cases. Glaucoma was present in 5 cases, including 2 of ours. Buphthalmia and
keratopathy secondary to glaucoma were also observed. White eyelashes, seen only
in our cases, may be a sign of "early senility." CONCLUSIONS: Optic atrophy is
not a constant finding in GAPO syndrome. Glaucoma may accompany the ocular
findings. This syndrome has been attributed to either ectodermal dysplasia or the
accumulation of extracellular connective tissue matrix, due to an enzyme
deficiency involved in its metabolism. Current studies show that an elastin
defect and secondary changes in collagen may be important in the pathogenesis of
the disease.
PMID- 10197744
TI - Ocular surface disease in atopic dermatitis.
AB - PURPOSE: To describe the ocular surface disorders of 362 patients with severe
active atopic dermatitis (AD) treated in the Ophthalmology Department of Kobe
University Hospital and Kobe Rosai Hospital Eye Clinics during the period 1994
1996. METHODS: Routine ophthalmic examinations as well as tear film break-up time
(BUT) and Schirmer tests were carried out. RESULTS: Lid eczema (65.7%), atopic
keratoconjunctivitis, and superficial punctate keratopathy (67.5%) were the
dominant ocular diseases in these patients. Tear function tests showed a BUT
value of less than 10 seconds in 62.4% of the eyes and a Schirmer test value of
less than 5 mm in 56.2% of the eyes. CONCLUSIONS: A careful examination of the
ocular surface is essential in treating AD patients. We also suggest that the
ocular surface disorders in AD may be due to allergic reactions and disorders in
tear film quantity or quality.
PMID- 10197745
TI - Difference in the effects of radioprotection between aerial and root parts of
Lycium chinense.
AB - Radiation protection from bone marrow death by consecutive injections of crude
extracts from different parts of Lycium chinense (LC), root (LCR) and aerial part
(LCA), before whole body X-irradiation was confirmed by tests with ICR strain
mice. Both extracts were effective after intraperitoneal injection of a high
dose, once a day, for seven consecutive days before irradiation. Based on the
studies of endogenous hematopoietic spleen colony formation (CFUs), and the
postirradiation behavior of hematograms and hematocrits, it was demonstrated that
the LCR protects mice more effective when given in a dose of 500 mg/kg. Enhanced
CFUs was found in the irradiation range of 4-8 Gy by various treatments. Recovery
of leukocyte, erythrocyte and thrombocyte counts was significantly stimulated by
the extract of LCR with 500 mg/kg administration. Stimulated recovery by the
extract from the LCR was also observed in hematocrit. On the contrary, the
extracts of both LCA and LCR did not markedly affect recovery of leukocyte,
erythrocyte, thrombocyte counts and hematocrits by 250 mg/kg administration. It
could be deduced that the uncertainly radioprotective action is induced by a
possible process of enhanced regeneration of the hematopoietic stem cells due to
either enhanced postirradiation repair or an increased proliferation of the
hematopoietic stem cells under the suitable extract administration.
PMID- 10197746
TI - Stimulation of interleukin-1 and -6 production in alveolar macrophages by the
neotropical liana, Uncaria tomentosa (una de gato)
AB - Two extracts of different collections of the traditional medicine una de gato
(Uncaria tomentosa) from Peru were characterized by High Pressure Liquid
Chromatography as containing approximately 6 mg/g total oxindole content prior to
studies with alveolar macrophages. The plant preparations greatly stimulated IL-1
and IL-6 production by rat macrophages in a dose dependent manner in the range of
0.025-0.1 mg/ml. They were also able to enhance IL-1 and -6 in lipopolysaccharide
stimulated macrophages. The results suggest a strong immunostimulant action of
this plant.
PMID- 10197747
TI - Anti-inflammatory activity of the crude extract from the fruits of Pterodon
emarginatus Vog.
AB - The vegetal species Pterodon emarginatus Vog. (Leguminosae/Papilonaceae),
popularly known in Brazil as 'sucupira branca', is widely used by domestic
medicine as an anti-inflammatory. From these observations, the hexanic crude
extract (HCE) of the fruits was obtained and submitted for assessment of its anti
inflammatory activity. For this purpose, the following tests were used: (1)
Determination of ED50 and LD50; (2) Paw edema induced by carrageenin, dextran,
histamine and nystatin; (3) Peritonitis caused by carrageenin and (4) Granuloma
test. The ED50 (oral) in the edema induced by carrageenin was 500 mg/kg, and LD50
(oral) was 4.02 g/kg. In the edema caused by nystatin, there was a significant
inhibition by 45% (P < 0.05 student's t-test) at the 6th hour following the
treatment. In the granuloma test performed in animals treated with HCE, there was
an inhibition of the granulomatous tissue formation by 22%. The migration of
neutrophils towards the peritoneal cavity was inhibited in HCE treated animals by
43% (P < 0.05). However, in the edema caused by dextran and histamine, there was
no significant response in HCE treated animals.
PMID- 10197748
TI - Medicinal plants from Nepal; II. Evaluation as inhibitors of lipid peroxidation
in biological membranes.
AB - In an ethnopharmacological screening of selected Nepalese medicinal plants, the
inhibitory effect on lipid peroxidation of 36 methanolic extracts of 28 different
plant species were evaluated using bovine brain phospholipid liposomes as model
membranes. The most potent inhibitor with an IC50 value of 0.93 microg/ml was the
extract obtained from the bark of Clerodendrum indicum. The extracts obtained
from Aglaia roxburghiana fruits, Euonymus pendulus barks and Emblica officinalis
fruits were also active and inhibited lipid peroxidation with IC50 values of 10,
12 and 13 microg/ml, respectively. The most active extracts were from indigenous
plants traditionally used to treat inflammatory diseases.
PMID- 10197749
TI - Studies on the preventive effect of Spirulina maxima on fatty liver development
induced by carbon tetrachloride, in the rat.
AB - The aim of the present work was to assess if the feeding of either the oil
extract of Spirulina maxima or of its defatted fraction would prevent fatty liver
development, induced in rats by a single intraperitoneal dose of carbon
tetrachloride (CCl4). Liver and serum lipids were evaluated 4 days after
treatment with this agent. Concentration of liver lipids did not differ in rats
fed on a purified diet either without or with one of the fractions of Spirulina,
except for total cholesterol, which showed a slight increase in the group
receiving the oil extract of Spirulina. However, after CCl4 treatment, liver
total lipids and triacylglycerols were significantly lower in rats fed on a diet
containing any fraction of Spirulina (defatted or the oil fraction) than in rats
without Spirulina in their diet. Furthermore, the increased liver cholesterol
values, induced by CCl4 treatment, were not observed in rats receiving Spirulina.
In addition, rats receiving whole Spirulina in their diet and treated only with
the vehicle showed an increase in the percentage of HDL values. The changes in
VLDL and LDL induced by CCl4 treatment were not observed in the whole Spirulina
group. Furthermore, after CCl4 treatment the values of the liver microsomal
thiobarbituric acid-reactive substances were lower in the whole Spirulina group
than in the control group. These results support the potential hepatoprotective
role of Spirulina.
PMID- 10197750
TI - Xanthine oxidase inhibitory activity of northeastern North American plant
remedies used for gout.
AB - Xanthine oxidase (xanthine: oxygen oxidoreductase EC 1.2.3.2) inhibitory activity
was assayed from 26 species belonging to 18 families traditionally used for the
treatment of gout and related symptoms by Indigenous people of northeastern North
America. The degree of inhibition was determined by measuring the increase in
absorbance at 295 nm associated with uric acid formation. Eighty-eight percent of
the plants were found to have inhibitory activity at 100 microg/ml, with 20%
having greater than 50% inhibition. Larix laricina exhibited the highest activity
with an inhibition of 86.33%. Of the species with the highest activity,
Lineweaver-Burk plots showed that inhibition mode was of linear mixed-type.
Inhibitory activity of the plants correlated positively with their phenolic
content (r = 0.52 P < 0.01) and tannin content (r = 0.59 P < 0.001).
PMID- 10197751
TI - Antihistaminic and anticholinergic activity of barberry fruit (Berberis vulgaris)
in the guinea-pig ileum.
AB - Barberry (Berberis vulgaris) is a well known medicinal plant in Iran and has also
been used as food. The antihistaminic and anticholinergic activity of aqueous
extract of barberry fruits were investigated on isolated guinea-pig ileum, and
dose response curves of histamine and acetylcholine with and without extract were
plotted. The pA2 values for antihistaminic activity of extract and
dexchlorpheniramine were calculated (extract; pA2 +/- S.E.M. = 4.50 +/- 0.01[-log
C (g/l)]; dexchlorpheniramine; pA2 +/- S.E.M. = 9.36 +/- 0.14[-log C (M)]) and
compared with each other. The pA2 values for anticholinergic activity of extract
and atropine were also calculated (extract, pA2 +/- S.E.M. = 4.37 +/- 0.03[-log C
(g/l)]; atropine, pA2 +/- S.E.M. = 8.99 +/- 0.13[-log C (M)]) and compared. The
results indicated antihistaminic and anticholinergic activity of extract that
seems to be of the competitive type.
PMID- 10197752
TI - Evaluation of the anticonvulsant activity of the essential oil of Eugenia
caryophyllata in male mice.
AB - In this study, the effect of an essential oil of Eugenia caryophyllata
(Myrtaceae), an antiepileptic remedy in Iranian folk medicine, against seizures
induced by maximal electroshock (MES) or pentylenetetrazole (PTZ) in male mice
was studied. The essential oil exhibited anticonvulsant activity against tonic
seizures induced by MES. Although it was not effective against clonic convulsions
induced by intraperitoneal administration of PTZ, the seizure threshold which was
determined by an increase in the dose of intravenously infused PTZ required to
induce clonus, was elevated by the essential oil. In addition, at some
anticonvulsant doses, the essential oil produced motor impairment on the rotarod.
PMID- 10197753
TI - Anti-inflammatory activity of flavone and some of its derivates from Virola
michelli Heckel.
AB - The phytochemical study using Virola michelli Heckel (Myristicaceae) leaves
allowed the isolation of a flavone named titonine (7,4'-dimethoxy-3'
hydroxyflavone). Titonine was further submitted to methylation and acetylation
reactions yielding a 7,3',4'-trimethoxyflavone and a 7,3'-dimethoxy-4'
acetylflavone, respectively. These compounds were evaluated for both anti
inflammatory and analgesic activity. The anti-inflammatory activity was evaluated
in rats using the paw edema test with carrageenin, while the analgesic activity
was determined in mouse using the writhing test method. The different animal
groups were treated with three compounds (10 mg/kg -i.p.) thirty min prior to
stimuli application. The inhibition levels obtained for each compound were 22, 41
and 68%, respectively. Using the writhing test, oral doses of 5, 10 and 15 mg/kg
of natural flavone reduced the acetic acid-induced contortions in a dose
dependent manner.
PMID- 10197754
TI - Preliminary studies on the inorganic constituents of some indigenous
hypoglycaemic herbs on oral glucose tolerance test.
AB - Medicinal herbs used in indigenous medicines in crude forms for the management of
diabetes mellitus, contain both the organic and inorganic constituents. It is
known that certain inorganic mineral elements (potassium, zinc, calcium, traces
of chromium, etc.) play an important role in the maintenance of normal glucose
tolerance and in the release of insulin from beta cells of islets of Langerhans.
In the present study, 30 hypoglycaemic herbs were selected from indigenous folk
medicines, Ayurvedic, Unani and Siddha systems of medicines. Special emphasis was
given to their inorganic parts by carefully preparing ash (which contains mainly
mineral elements) of the specific parts of the herbal samples under study. Next,
the single dose effect on the oral glucose tolerance test (GTT) was studied using
previously fasted albino rats. Similar effects were also compared with their
organic parts of the concerned herbal samples in the form of 95% ethanolic
extracts. In certain inorganic samples, more pronounced action (as glucose
tolerance factor) were noticed than their corresponding organic parts.
PMID- 10197755
TI - Quantitative analysis of aristolochic acids, toxic compounds, contained in some
medicinal plants.
AB - The amounts of aristolochic acid I and II in four groups of medicinal plants from
the Aristolochiaceae and some related plants were determined by high-pressure
liquid chromatography, for Aristolochia was reported to produce interstitial
nephritis caused by aristolochic acids during chronic use for the treatment of
rheumatism, diuretic and analgesic. They were detected in all the plants that
originated from the genus Aristolochia (Aristolochiaceae) and in some of the
plants from the genus Asarum (Aristolochiaceae). The present results suggest that
these medicinal plants should be prohibited to use for remedy due to the harmful
effects attributed to aristolochic acids.
PMID- 10197756
TI - The effectiveness of light on the circadian clock is linked to its emotional
value.
AB - Studies carried out within the primary visual system have shown that neural
responses to light stimuli transmitted via the retinogeniculate pathway are
significantly altered when these stimuli are made aversive through conditioning.
The effect of such aversive conditioning on neural responses to light transmitted
within the circadian visual system has not been investigated. In mammals, the
principal projection of the circadian visual system, the retinohypothalamic
tract, is functionally and anatomically distinct from the primary visual pathway
allowing for direct transmission of light from the retina to the suprachiasmatic
nucleus of the hypothalamus, the circadian clock. Light transmitted within this
pathway is essential for entrainment of circadian rhythms providing the critical
stimulus for resetting the circadian clock. We asked whether the response of
neural elements within the suprachiasmatic nucleus to a resetting light stimulus
would be altered if that stimulus had acquired aversive properties through
conditioning. To study this we assessed the effect of a light stimulus made
aversive through pairings with footshock on a cellular correlate of clock
resetting, the expression of the transcription factor Fos in neurons of the
suprachiasmatic nucleus. We show that Fos expression in the suprachiasmatic
nucleus in response to light previously paired with footshock is significantly
suppressed. This finding provides the first evidence that the effectiveness of a
light as a resetting stimulus can be modulated by its conditioned aversive
properties.
PMID- 10197757
TI - Estimation of single channel conductance underlying synaptic transmission between
pyramidal cells in the visual cortex.
AB - Axon collaterals originating from pyramidal cells are one of the most abundant
presynaptic elements in the neocortical circuits. To understand a quantitative
aspect of synaptic transmission between pyramidal cells, we attempted to estimate
single channel conductance by applying non-stationary noise analysis to unitary
excitatory postsynaptic currents. Simultaneous recordings were carried out in two
pyramidal cells of superficial layers in visual cortical slices. Unitary
postsynaptic currents, which were evoked by action potentials of presynaptic
cells impaled with conventional sharp electrodes, were recorded from postsynaptic
cells with whole-cell patch clamp techniques. Estimated single channel
conductance was 12.8 3.8(S.D.) pS for kittens and 10.4 +/- 1.5 pS for rats.
Dividing these values by the conductance for unitary postsynaptic currents, we
calculated the number of non-N-methyl-D-aspartate receptor channels activated
during the postsynaptic currents. The obtained estimates were 52 (kittens) and 41
(rats). To further estimate the number of channels involved in each quantal
event, we analysed amplitude histograms of miniature and spike-evoked excitatory
postsynaptic currents. The derived number of estimates from these two kinds of
histograms agreed quite well; about 20 channels were required for individual
quantal events. Assuming open probability of non-N-methyl-D-aspartate receptor
channels to be 0.7, our results suggest that the number of channels available for
synaptic transmission between individual pyramidal cells would be 74 (kittens)
and 59 (rats). We propose that at pyramidal-pyramidal synapses, the number of
open channels is several times smaller than that previously reported for the
synapses between geniculo-cortical afferent and layer IV spiny stellate cells.
PMID- 10197758
TI - Non-volatile general anaesthetics reduce spinal activity by suppressing plateau
potentials.
AB - Non-volatile general anaesthetics are thought to reduce brain activity by
potentiating inhibitory GABA(A) receptor channels but also cause adverse effects
by suppress ing L-type calcium channels in the heart. In sections of the spinal
cord, the non-volatile anaesthetics pentobarbital, thiopental and propofol
reduced excitability of sensorimotor neurons by suppressing plateau potentials
mediated by L-type calcium channels. This effect was independent of GABA(A)
receptor potentiation but occurred in an overlapping concentration range.
Therefore, the suppressive effect of non-volatile anaesthetics on L-type calcium
channels can contribute to the reduction of spinal sensorimotor activity during
anaesthesia. The results support the idea that general anaesthesia is achieved
through several mechanisms and suggest that procedures for anaesthesia may be
improved by combining selective agents for each mechanism in optimal
concentrations.
PMID- 10197759
TI - Cortistatin affects glutamate sensitivity in mouse hypothalamic neurons through
activation of sst2 somatostatin receptor subtype.
AB - Cortistatin is a 14-residue putative neuropeptide with strong structural
similarity to somatostatin. Even if it shares several biological properties with
somatostatin, the effects of cortistatin on cortical electrical activity and
sleep are opposite to those elicited by somatostatin. We recently demonstrated
that somatostatin could modulate glutamate sensitivity, either positively through
activation of the sstl receptor subtype, or negatively through activation of the
sst2 receptor subtype in hypothalamic neurons in culture which express almost
exclusively these two sst subtypes. Thus, in the present study we compared the
effects of cortistatin and somatostatin in hypothalamic neurons in culture, in
order to define the former peptide activity on both subtypes. We first determined
that the affinities of cortistatin and somatostatin were similar on cloned rat
sstl and sst2 receptor subtypes in transfected cells and hypothalamic neurons
membranes. We then found that cortistatin, like somatostatin, depresses the
glutamate response but, unlike somatostatin, never potentiates glutamate
sensitivity in hypothalamic neurons. The observed effect of cortistatin is
strongly suggestive of an activation of the somatostatin sst2 receptor subtype in
hypothalamic neurons in culture.
PMID- 10197760
TI - Analysis of spontaneous activity patterns of human thalamic ventrolateral neurons
and their modifications due to functional brain changes.
AB - In the human thalamic ventralis lateralis nucleus the spontaneous activity of 235
single units during 38 stereotactic operations in locally anaesthetized
parkinsonian patients was analysed. Two basic cell types (A and B) were shown to
exist in this nucleus: (i) with unitary irregular (2-40/s) discharges
characterized by a tendency to spike grouping in the range of 4-6 Hz and 10-30 Hz
(A-type, 74%), (ii) with bursting discharges firing in short trains (5-30 ms)
characterized by an unstable rhythmic 3-6 Hz pattern similar to a low-threshold
Ca2+ intrinsic burst structure of discharges (B-type, 26%). The functional brain
changes after a motor tests performance were accompanied by the appearance of two
different transient modifications of activity of A-cells pattern into rhythmic
burst discharges: (i) in the range of 3-6 Hz, similar to the bursts found for B
cells and recorded mainly in the anterior ventrolateral region in rigid patients,
(ii) in the range of 5 +/- 1 Hz, characterized by other interspike interval and
recorded in the posterior ventrolateral region in patients with tremor.
Modifications during short-term anaesthesia resulted in 10-15 Hz burst discharges
that were associated with gradual disappearance of A-cells activity. In contrast
to what happens for A-cells, the activity of bursting B-units was characterized
by an invariant intrinsic structure of discharges irrespective of the functional
brain changes or the forms of parkinsonian pathology. The nature of A- and B
units as well as the mechanisms of transient modifications of their spontaneous
activity patterns due to the functional brain changes are discussed.
PMID- 10197761
TI - Analysis of evoked activity patterns of human thalamic ventrolateral neurons
during verbally ordered voluntary movements.
AB - In the human thalamic ventralis lateralis nucleus the responses of 184 single
units to verbally ordered voluntary movements and some somatosensory stimulations
were studied by microelectrode recording technique during 38 stereotactic
operations on parkinsonian patients. The tests were carried out on the same
previously examined population of neurons classified into two groups, named A-
and B-types according to the functional criteria of their intrinsic structure of
spontaneous activity patterns. The evaluation of the responses of these units
during functionally different phases of a voluntary movement (preparation,
initiation, execution, after-effect) by means of the principal component analysis
and correlation techniques confirmed the functional differences between A- and B
types of neurons and their polyvalent convergent nature. Four main conclusions
emerge from the studies. (1) The differences of the patterns of A- and B-unit
responses during the triggering and the execution phases of a voluntary movement
indicate the functionally different role of these two cell types in the
mechanisms of motor signal transmission. (2) The universal non-specific form of
anticipatory A- and B-unit responses during the movement preparation and
initiation of various kinds of voluntary movements reflect the integrative
"triggering" processes connected with the processing and programming of some
generalized parameters of a motor signal and not with the performance of a
certain forthcoming motor act. (3) The expressed intensity of these "triggered"
non-specific processes in the anterior parts of the ventralis lateralis nucleus
indicates their relation not only to the motor but to the cognitive attentional
functions forming a verbally ordered voluntary movement. (4) The appearance of
the transient cross-correlations between the activities of adjacent A- and B
cells and also the synchronization of their 5 +/- 1 Hz frequency during and/or
after motor test performances point to the contribution of these two populations
to central mechanisms of the voluntary movement and the parkinsonian tremor. The
functional role of two A- and B-cell types is discussed with references to the
central mechanisms of verbally ordered voluntary movements and the parkinsonian
tremor.
PMID- 10197762
TI - Dark rearing blocks the developmental down-regulation of brain-derived
neurotrophic factor messenger RNA expression in layers IV and V of the rat visual
cortex.
AB - In this study, we describe the distribution of brain-derived neurotrophic factor
messenger RNA in the binocular primary visual cortex of the rat during postnatal
development, starting at postnatal day (P) 13. High-resolution non-isotopic in
situ hybridization combined with Nissl staining were used to quantify the number
of cells expressing brain-derived neurotrophic factor messenger RNA. At P13, most
of the cells express brain-derived neurotrophic factor messenger RNA. After eye
opening (P14-P15), the relative number of brain-derived neurotrophic factor
messenger RNA-positive cells decreases by a factor of two in layer IV, i.e. that
receiving the visual input, and in layer V. To verify the hypothesis that light
could trigger this decrease, pups were kept in complete darkness from birth. At
P22, pups reared in the dark were killed and the visual cortex processed for in
situ hybridization and northern blotting. The results obtained in dark-reared
animals prove that light deprivation can: (i) decrease the general levels of
brain-derived neurotrophic factor messenger RNA, and (ii) increase the relative
number of brain-derived neurotrophic factor messenger RNA-positive cells in
layers IV and V with respect to control rats. Exposure to light for five days
after the period of darkness restored the number of brain-derived neurotrophic
factor messenger RNA-positive cells. We conclude that the expression of brain
derived neurotrophic factor messenger RNA in the rat primary visual cortex is
regulated during development and that this process is under the control of visual
input.
PMID- 10197764
TI - Analysis of synaptotagmin I-IV messenger RNA expression and developmental
regulation in the rat hypothalamus and pituitary.
AB - Synaptotagmins are a large family of synaptic vesicle membrane proteins, that
appear to be involved in neurotransmitter secretion from small secretory
vesicles. We have quantitatively analysed the messenger RNA levels of
synaptotagmin I-IV isoforms in adult hypothalamic and pituitary tissues in order
to determine which of these isoforms dominate in these tissues which mainly
secrete peptides from large dense core vesicles. We also studied the expression
of these isoforms during prenatal (E15, and E17) and postnatal (P1, P7, P14 and
P21) rat hypothalamic development. In order to assay small individual samples
(e.g., pituitary and embryonic tissues), we employed quantitative reverse
transcription-polymerase chain reaction methods. Our results show that
synaptotagmin I messenger RNA is the most abundant isoform in all tissues, and is
about 5.4- or 38-fold higher in hypothalamus than in neurointermediate and
anterior pituitary lobe, respectively. Synaptotagmin II, which is very abundant
in cerebellum, is relatively low in hypothalamus (5% of cerebellum) and virtually
absent from the pituitary. Synaptotagmin III is about 10 times greater in the
neural tissues versus the pituitary, and synaptotagmin IV was the least abundant
isoform in all the tissues. Developmental analyses of the synaptotagmin isoforms
in rat hypothalamus shows that all isoforms are at low levels during embryonic
stages and increase postnatally. Synaptotagmin I and II have similar patterns and
rise to maximum (adult) levels around P14, whereas synaptotagmin III and IV reach
their maximum levels considerably earlier, at P1. These data show that
synaptotagmin I is the dominant isoform in both predominantly peptide secreting
systems (e.g., in pituitary tissues) and in neurotransmitter secreting systems
(e.g., in cerebellum). While the developmental expression patterns of
synaptotagmin I and II parallels the temporal development of synaptogenesis in
the nervous system, the early maximal expression of synaptotagmin III and IV
suggests that these isoforms may have other functions during early postnatal
development.
PMID- 10197763
TI - Neurotrophin activation of catecholamine storage vesicle protein gene expression:
signaling to chromogranin a biosynthesis.
AB - Nerve growth factor differentiates precursor cells into sympathetic neurons. Does
acquisition of a "neuronal" phenotype after nerve growth factor involve
biosynthesis of chromogranin A, the major soluble protein in chromaffin granule
cores? Nerve growth factor activated chromogranin A gene expression 7.6-fold in
PC12 pheochromocytoma cells, and similarly activated PC12-transfected mouse, rat
or human chromogranin A promoter/reporter constructs. Chromogranin A promoter 5'
deletions narrowed the nerve growth factor response element to a region from - 77
to - 61 bp upstream of the cap site, a region containing the chromogranin A
cyclic AMP response element (TGACGTAA). Three different site-directed mutations
of the cyclic AMP response element each reduced the nerve growth factor effect by
>90%. Transfer of the cyclic AMP response element to a heterologous (thymidine
kinase) promoter activated that promoter approximately 5-fold after nerve growth
factor, while transfer of a cyclic AMP response element point-gap mutant (TGA
GTAA) to a heterologous promoter abolished the nerve growth factor effect. These
findings indicate that the cyclic AMP response element in cis is, at least in
part, both necessary and sufficient to activate the chromogranin A gene. Chemical
blockade of the nerve growth factor receptor TrkA or the mitogen-activated
protein kinase pathway component MEK substantially diminished nerve growth factor
induced expression of chromogranin A. By contrast, the response of chromogranin A
to nerve growth factor was not impaired after blockade of phospholipase C-gamma
or phosphoinositide-3 kinase. Chemical blockade of TrkA, Ras, MEK or mitogen
activated protein kinase similarly inhibited nerve growth factor activation of
chromogranin A. Expression of constitutively activated Ras, Raf or MEK mutants
increased chromogranin A promoter activity. Expression of dominant negative
(inhibitory) mutants of Sos, Ha-Ras, Rafl, mitogen-activated protein kinase,
ribosomal protein S6 serine kinase II (CREB kinase) or CREB (KCREB) each
inhibited the nerve growth factor-induced increase in chromogranin A promoter
activity. Thus, each component of the mitogen-activated protein kinase pathway is
crucially involved in relaying the nerve growth factor signal in trans to the
chromogranin A gene, in the following proposed sequence: nerve growth factor -->
TrkA --> Shc/Grb2/Sos --> Ras --> Raf --> MEK --> mitogen-activated protein
kinase --> ribosomal protein S6 serine kinase II --> CREB cyclic AMP response
element.
PMID- 10197765
TI - Syntaxin 1A and 1B display distinct distribution patterns in the rat peripheral
nervous system.
AB - Syntaxin 1 has been shown to play an outstanding role in synaptic vesicle
exocytosis. Two isoforms of this protein are expressed in neurons, syntaxin 1A
and 1B. However, the physiological significance of the occurrence of such closely
related isoforms is not still understood. Here, by means of isoform-specific
immunocytochemistry, we show that syntaxin 1A and 1B display different patterns
of expression in the rat peripheral nervous system. Nerve terminals of sensory
neurons reaching the spinal cord were clearly enriched in immunoreactive syntaxin
1A. Both isoforms were detected in cell bodies of sensory neurons at the dorsal
root ganglia, although specific immunolabelling displayed very different patterns
at the cellular level. Motor endplates and muscle spindles were only
immunostained for syntaxin 1B. Syntaxin 1A was mainly associated with nerve
fibres reaching small blood vessels. In addition, nerve plexuses of the enteric
nervous system showed immunostaining for both syntaxin isoforms. The different
distribution pattern of the two neuronal syntaxin isoforms in the rat peripheral
nervous system could be related to isoform-specific biochemical properties
involved in the exocytotic process.
PMID- 10197766
TI - Connexin30 in rodent, cat and human brain: selective expression in gray matter
astrocytes, co-localization with connexin43 at gap junctions and late
developmental appearance.
AB - We previously presented evidence [Nagy et al. (1997) Neuroscience 78, 533-548]
that, in addition to their ubiquitous expression of connexin43, astrocytes
produce a second connexin suggested to be connexin30, a recently discovered
member of the family of gap junction proteins. A connexin30 specific antibody was
subsequently developed and utilized here to confirm and extend our earlier
observations. On western blots, this antibody detected a 30,000 mol. wt protein
in rat, mouse, cat and human brain, and exhibited no cross-reaction with
connexin43, connexin26 or any other known connexins expressed in brain.
Immunohistochemically, connexin30 was localized in astrocytes, at gap junctions
between these cells and on the astrocyte side of gap junctions between astrocytes
and oligodendrocytes. Double labelling revealed co-localization of connexin30 and
connexin43 at astrocytic gap junctions. Punctate immunolabelling patterns for
both connexins were qualitatively similar, but differences were evident. In
contrast to regional connexin43 expression, diencephalic and hindbrain areas
exhibited considerably greater expression than forebrain areas, subcortical
perivascular astrocytic endfeet were more heavily labelled for connexin30, white
matter tracts such as corpus callosum, internal capsule and anterior commissure
were devoid of connexin30, and appreciable levels of connexin30 during
development were not seen until about postnatal day 15. These results indicate
that connexin30 is expressed by gray, but not white matter astrocytes, its
distribution is highly heterogeneous in gray matter, it is co-localized with
connexin43 at astrocytic gap junctions where it forms homotypic or heterotypic
junctions, and its emergence is delayed until relatively late during brain
maturation. Taken together, these results suggest that astrocytic connexin30
expression at both regional and cellular levels is subject to regulation in adult
brain as well as during brain development.
PMID- 10197767
TI - Embryonic striatal grafts restore neuronal activity of the globus pallidus in a
rodent model of Huntington's disease.
AB - It has been demonstrated in rats that embryonic striatal grafts placed in the
excitotoxically lesioned striatum establish neuronal connections with the host
globus pallidus. In order to determine whether the morphologically verified
connections between the grafts and host are functional, the present study
investigated the effects of embryonic striatal grafts on changes in the neuronal
activity of the globus pallidus in rats with quinolinic acid-induced striatal
lesions. The activity of pallidal neurons was determined by use of quantitative
cytochrome oxidase histochemistry and an electrophysiological technique. Striatal
lesions induced an increase in both the cytochrome oxidase activity and the
spontaneous firing rate of the globus pallidus ipsilateral to the lesions. Grafts
derived from the lateral ganglionic eminence, but not the medial ganglionic
eminence, reversed the lesion-induced increase in the cytochrome oxidase activity
of the globus pallidus with concomitant reduction of apomorphine-induced
rotational asymmetry. The lateral ganglionic eminence grafts also attenuate the
increase in the firing rate of pallidal neurons in rats with striatal lesions.
The present results provide evidence that striatal lesions lead to the loss of a
tonic inhibitory input to the globus pallidus with consequent increase in the
activity of pallidal neurons, and that intrastriatal striatal grafts reverse the
altered activity of pallidal neurons. The findings strongly suggest that
embryonic striatal grafts functionally repair the damaged striatopallidal
pathway.
PMID- 10197768
TI - Ca2+-activated outward currents in neostriatal neurons.
AB - Whole-cell voltage-clamp recordings of outward currents were obtained from
acutely dissociated neurons of the rat neostriatum in conditions in which inward
Ca2+ current was not blocked and intracellular Ca2+ concentration was lightly
buffered. Na+ currents were blocked with tetrodotoxin. In this situation, about
53 +/- 4% (mean +/- S.E.M.; n = 18) of the outward current evoked by a
depolarization to 0 mV was sensitive to 400 microM Cd2+. A similar percentage was
sensitive to high concentrations of intracellular chelators or to extracellular
Ca2+ reduction (<500 microM); 35+/-4% (n=25) of the outward current was sensitive
to 3.0 mM 4-aminopyridine. Most of the remaining current was blocked by 10 mM
tetraethylammonium. The results suggest that about half of the outward current is
activated by Ca2+ entry in the present conditions. The peptidic toxins
charybdotoxin, iberotoxin and apamin confirmed these results, since 34 +/- 5% (n
= 14), 29 5% (n= 14) and 28 +/- 6% (n=9) of the outward current was blocked by
these peptides, respectively. The effects of charybdotoxin and iberotoxin added
to that of apamin, but their effects largely occluded each other. There was
additional Cd2+ block after the effect of any combination of toxins. Therefore,
it is concluded that Ca2+-activated outward currents in neostriatal neurons
comprise several components, including small and large conductance types. In
addition, the present experiments demonstrate that Ca2+-activated K+ currents are
a very important component of the outward current activated by depolarization in
neostriatal neurons.
PMID- 10197769
TI - Paradoxical inhibition of nociceptive neurons in the dorsal horn of the rat
spinal cord during a nociceptive hindlimb reflex.
AB - Nociceptive-specific and multireceptive neurons in the lumbar dorsal horn are
excited by noxious stimuli applied to the hindpaw and inhibited by noxious
stimuli applied to distant body regions. Given that at least a subset of these
neurons are part of the circuit for nociceptive reflexes, inhibition of
nociceptive-specific and multireceptive neurons should inhibit nociceptive
reflexes. Unfortunately, previous attempts to test this hypothesis have been
inconclusive because of methodological differences between electrophysiological
and behavioral experiments. The present study overcame this problem by recording
neural and reflex activity simultaneously. Rats were anesthetized with halothane
and surgically prepared for single-unit recording from the lumbar dorsal horn.
Hindpaw heat caused a burst of activity that reliably preceded hindpaw withdrawal
in 10 nociceptive-specific and 17 multireceptive neurons. A distant noxious
stimulus (tail in 50 degrees C water or ear pinch) inhibited the evoked activity
of both nociceptive-specific and multireceptive neurons and simultaneously
changed the topography of the hindpaw reflex from flexion to extension without
altering reflex latency. The present data are consistent with previous reports of
inhibition of nociceptive-specific and multireceptive neurons during application
of a distant noxious stimulus. However, inhibition of nociceptive-specific and
multireceptive neurons concomitant with a shift in the hindlimb reflex from
flexion to extension suggests that these neurons are part of the circuit for
flexor reflexes specifically. Presumably, lateral inhibition from the flexor to
extensor circuit allows for the release of hindlimb extension when neurons in the
flexion circuit are inhibited by a distant noxious stimulus. Such a system
reduces the chance of injury by allowing for withdrawal reflexes to a single
noxious stimulus and escape reactions, such as running and jumping, to multiple
noxious stimuli.
PMID- 10197770
TI - Descending modulation of opioid-containing nociceptive neurons in rats with
peripheral inflammation and hyperalgesia.
AB - Inflammation and hyperalgesia induce a dramatic up-regulation of opioid messenger
RNA and peptide levels in nociceptive neurons of the spinal dorsal horn.
Descending axons modulate nociceptive transmission at the spinal level during
inflammatory pain, and may play a role in the development of persistent pain. The
role of descending bulbospinal pathways in opioid-containing nociceptive neurons
was examined. Removal of descending inputs to the spinal cord was performed by
complete spinal transection at the midthoracic level. Seven days after spinal
transection, rats received a unilateral hindpaw injection of complete Freund's
adjuvant, a noxious stimulus that produces inflammation and hyperalgesia. Tissues
from the L4 and L5 segments of the spinal cord were removed and analysed by
northern blotting and immunocytochemistry. Spinal transection resulted in a
further increase in both dynorphin and enkephalin messenger RNA content following
complete Freund's adjuvant injection. There was a similar distribution and number
of dynorphin-immunoreactive cells in transected rats compared to rats which
received sham surgery. These data suggest that increased dynorphin messenger RNA
ipsilateral to inflammation, in rats without descending axons, was due to
increased expression within the same cells and not to recruitment of additional
dynorphin-expressing cells. This reflects a greater dynamic response of
nociceptive neurons to noxious stimuli in the absence of descending modulation.
Therefore, the net effect of descending afferents on spinal nociceptive circuits
may be to reduce the response of opioid-containing neurons to noxious stimulation
from the periphery.
PMID- 10197771
TI - Influence of functional glia on the electrophysiology of Purkinje cells in
organotypic cerebellar cultures.
AB - Previous studies have shown that exposure of organotypic cerebellar explants to
cytosine arabinoside (Sigma) for the first five days in vitro drastically reduced
the granule cell population and severely affected glial function. Myelination was
absent and astrocytes failed to ensheath Purkinje cells. In the absence of
astrocytic ensheathment, Purkinje cell somata became hyperinnervated by Purkinje
cell recurrent axon collaterals. Recurrent axon collaterals also projected to
Purkinje cell dendritic spines. In later studies, exposure of cerebellar cultures
to a different formulation of cytosine arabinoside (Pfanstiehl) also affected
granule cells and oligodendrocytes but did not compromise astrocyte function. The
different susceptibility of astrocytes to the two preparations of cytosine
arabinoside (Sigma and Pfanstiehl) has provided the opportunity to examine the
electrophysiological properties of Purkinje cells in the presence and absence of
functional glia. Ensheathed Purkinje cells in granuloprival cultures exhibit
within two weeks in vitro similar passive membrane properties as Purkinje cells
in control cultures. Their input resistance is significantly higher and their
spontaneous single-unit discharge is significantly lower than that of
unensheathed Purkinje cells. This effect suggests that ensheathed Purkinje cells
in cytosine arabinoside (Pfanstiehl)-treated cultures are more responsive to the
profuse Purkinje cell recurrent axon collateral inhibitory projection to
dendritic spines. These studies also show that the presence of functional glia
and/or astrocytic ensheathment can be correlated with the development of complex
spike activity by Purkinje cells in vitro. Purkinje cells in cultures treated
with cytosine arabinoside (Pfanstiehl), which does not compromise astrocytic
ensheathment, display membrane conductances and spike activity similar to mature
Purkinje cells in control cultures. By contrast, Purkinje cells in cultures
treated with cytosine arabinoside (Sigma), and devoid of astrocytic ensheathment,
display mainly simple spike activity reminiscent of the type of activity seen in
less mature neurons.
PMID- 10197772
TI - Localization of calcium-binding proteins and GABA transporter (GAT-1) messenger
RNA in the human subthalamic nucleus.
AB - The distribution of messenger RNA encoding the human GAT-1 (a high-affinity GABA
transporter) was investigated in the subthalamic nucleus of 10 neurologically
normal human post mortem cases. Further, the distribution of messenger RNA and
protein encoding the three neuronally expressed calcium-binding proteins
(calbindin D28k, parvalbumin and calretinin) was similarly investigated using in
situ hybridization and immunohistochemical techniques. Cellular sites of
calbindin D28k, parvalbumin, calretinin and GAT-1 messenger RNA expression were
localized using human-specific oligonucleotide probes radiolabelled with
[35S]dATP. Sites of protein localization were visualized using specific anti
calbindin D28k, anti-parvalbumin and anti-calretinin antisera. Examination of
emulsion-coated tissue sections processed for in situ hybridization revealed an
intense signal for GAT-1 messenger RNA within the human subthalamic nucleus,
indeed the majority of Methylene Blue-counterstained cells were enriched in this
transcript. Further, a marked heterogeneity was noted with regard to the
expression of the messenger RNA's encoding the three calcium-binding proteins;
this elliptical nucleus was highly enriched in parvalbumin messenger RNA-positive
neurons and calretinin mRNA-positive cells but not calbindin messenger RNA
positive cells. Indeed, only an occasional calbindin messenger RNA-positive cell
was detected within the mediolateral extent of the nucleus. In marked contrast,
numerous parvalbumin messenger RNA-positive cells and calretinin messenger RNA
positive cells were detected and they were topographically distributed;
parvalbumin messenger RNA-positive cells were highly enriched in the dorsal
subthalamic nucleus extending mediolaterally; calretinin messenger RNA-positive
cells were more enriched ventrally although some degree of overlap was apparent.
Computer-assisted analysis of the average cross-sectional somatic area of
parvalbumin, calretinin and GAT-1 messenger RNA-positive neurons revealed them
all to be in the range of 300 microm2. The unique patterns of calcium-binding
protein gene expression were similarly reflected at the protein level; an
abundance of parvalbumin- and calretinin-immunopositive neurons were observed
whereas only occasional intensely-labelled calbindin-immunopositive fibres were
seen, no calbindin-immunopositive cells were detected. Single and double
labelling studies show that parvalbumin-immunopositive neurons were mainly
localized in the dorsal region of the nucleus, and calretinin-immunopositive
neurons were mainly localized in the ventral region although there was overlap
with double-labelled neurons located in the middle and dorsal regions. The
significance of these findings, in particular the expression of GAT-1, a high
affinity GABA uptake protein, for basal ganglia signalling is discussed.
PMID- 10197773
TI - Calretinin-immunoreactive neurons in primate pedunculopontine and laterodorsal
tegmental nuclei.
AB - Single- and double-antigen localization procedures were used to study the
distribution, morphological characteristics and chemical phenotype of neurons
containing the calcium-binding protein calretinin in the pedunculopontine and
laterodorsal tegmental nuclei of the cynomolgus monkey (Macaca fascicularis).
Calretinin was detected in neurons that belonged to a highly heteromorphic and
widely distributed subpopulation of the pedunculopontine and laterodorsal
tegmental nuclei in the cynomolgus monkey. Double-immunostaining experiments
revealed that about 12% of these calretinin-containing neurons displayed
immunoreactivity for another calcium-binding protein, Calbindin-D28k. The
calretinin/Calbindin-D28k double-labeled neurons had small to medium-sized
perikarya, from which emerged a bipolar or multipolar dendritic arborization.
Calretinin was also present in approximately 8% of the cholinergic neurons of the
pedunculopontine/laterodorsal nuclear complex, as visualized on single sections
immunostained for both calretinin and choline acetyltransferase. These
calretinin/choline acetyltransferase double-labeled neurons displayed markedly
different sizes and shapes, and occurred preferentially in the pars compacta and
dissipata of the pedunculopontine tegmental nucleus. Numerous calretinin
immunoreactive fibers were also present within and around the superior cerebellar
peduncle. Some of these varicose fibers closely surrounded large non
immunoreactive neurons, as well as large neurons staining positively for choline
acetyltransferase. This study provides the first evidence for the existence of
calretinin-immunoreactive neurons within the primate pedunculopontine and
laterodorsal tegmental nuclei. Our data suggest that calretinin may play a role
in the function of the pedunculopontine/laterodorsal nuclear complex by acting
either alone or in conjunction with acetylcholine or Calbindin-D28k.
PMID- 10197774
TI - Regulation of the transmitter phenotype of rostral and caudal groups of cultured
serotonergic raphe neurons.
AB - We have studied the regulation of survival and serotonergic markers by
neurotrophins and several trophically active cytokines in neurons cultured from
the embryonic rat raphe region under defined conditions. At embryonic day 14,
saturating concentrations of brain-derived neurotrophic factor, neurotrophin-3,
neurotrophin-4 and basic fibroblast growth factor elicited a two- to 2.5-fold
increase in numbers of tryptophan hydroxylase- and serotonin-immunoreactive
neurons over a four-day culture period. Transforming growth factor beta-1 and
glial cell line-derived neurotrophic factor were less potent, while fibroblast
growth factor-5 was only marginally effective. Distinct responses to different
factors were noted depending on embryonic age and regional origin of serotonergic
neurons. Thus, brain-derived neurotrophic factor augmented numbers of tryptophan
hydroxylase-positive neurons at embryonic day 16 by a factor of seven, but only
1.5- to two-fold when cultures were established from day 13 or 14 embryos. In
cultures of rostral serotonergic groups (B4-B9), numbers of tryptophan
hydroxylase-positive neurons decreased in the absence of factors, whereas numbers
of tryptophan hydroxylase-immunoreactive neurons in cultures from caudal
serotonergic groups (B1-B3) increased during a 12-day culture period. There was
no evidence that serotonergic neurons undergo apoptosis (as visualized by
terminal deoxynucleotidyl transferase dUTP nick end labeling) or proliferate (as
visualized by 5-bromodeoxyuridine incorporation) in culture. Numbers of
serotonergic neurons also increased when cultures were treated with a brief 24-h
pulse of brain-derived neurotrophic factor, supporting the notion that changes in
numbers of serotonergic neurons reflected alterations of phenotype rather than
cell death or proliferation. The ability of cells to specifically take up the
serotonin analog 5,7-dihydroxytryptamine was also up-regulated by brain-derived
neurotrophic factor in both rostral and caudal raphe cultures. Lability of the
serotonergic phenotype was further suggested by the observation that ciliary
neurotrophic factor fully prevented the brain-derived neurotrophic factor
mediated increase in tryptophan hydroxylase-positive neurons. The effect of
ciliary neurotrophic factor was dependent on the presence of astrocytes. We
conclude that serotonergic neurons show spatially and temporally distinct
responses to neurotrophic factors, which seem to have a profound influence of the
transmitter phenotype rather than on survival.
PMID- 10197775
TI - Enhancement of neuronal survival by 6R-tetrahydrobiopterin.
AB - Recently, we have reported that 6R-tetrahydrobiopterin activates Ca2+ channels in
neuronal cells independently of its cofactor activities. Several reports indicate
that depolarization-induced activation of Ca2+ channels enhances neuronal
survival. Here, we investigated the effects of 6R-tetrahydrobiopterin on survival
of differentiated PC12 cells. Depletion of serum and nerve growth factor caused
cell death, which was prevented by high potassium. 6R-Tetrahydrobiopterin also
prevented death of PC12 cells cultured without serum and nerve growth factor in a
dose-related manner at physiological concentrations (1-100 microM). However,
surviving cells cultured with 6R-tetrahydrobiopterin showed undifferentiated
form. 6S-Tetrahydrobiopterin, a diastereoisomer of 6R-tetrahydrobiopterin, also
had a cell-surviving effect, but it was less potent as compared with that of 6R
tetrahydrobiopterin. The cell-surviving effect of 6R-tetrahydrobiopterin was
eliminated by a Ca2+ channel blocker, but persisted in the presence of an
inhibitor for tyrosine hydroxylase, dopamine, L-DOPA, an inhibitor for nitric
oxide synthase and a nitric oxide generator. The effect of 6R-tetrahydrobiopterin
was mimicked by a cyclic-AMP analogue and inhibited by an inhibitor for protein
kinase A. Ca2+ channel activity was preserved but dopamine-releasing activity was
disturbed in surviving cells cultured with 6R-tetrahydrobiopterin. 6R
Tetrahydrobiopterin had no effect on mitogen-activated protein kinase. These
findings suggest that, independently of its cofactor activities and mitogen
activated protein kinase cascade, 6R-tetrahydrobiopterin enhances survival of
PC12 cells by activating Ca2+ channels via the cyclic-AMP-protein kinase A
pathway, but that 6R-tetrahydrobiopterin does not preserve neuronal character
induced by nerve growth factor.
PMID- 10197776
TI - Stress induces neurogenesis in non-neuronal cell cultures of adult olfactory
epithelium.
AB - Among the basal cells of the olfactory epithelium is a stem cell which divides
and whose progeny differentiate into new sensory neurons throughout adult life.
Olfactory neurogenesis is highly regulated, for example it is stimulated by
epithelial damage. Previous reports implicate several growth factors in
progenitor cell proliferation and neuronal differentiation in vitro but these
studies differ in growth conditions and age of donors making it difficult to
determine precisely the roles of neurogenic stimuli and their sites of action.
The aims of the present study were to develop purified basal cell cultures from
adult olfactory epithelium and to stimulate neurogenesis in defined growth
conditions in order to elucidate the cellular mechanisms by which neurogenesis is
stimulated after epithelial damage. We show here that differentiated olfactory
sensory neurons arise after biochemical or mechanical stress of rat and mouse
olfactory epithelial cell cultures in the absence of growth factors, complex
media (e.g., serum, conditioned media, pituitary and hypothalamic extracts), or
other cells (e.g., explants, feeder layers of glia, or other non-epithelial
cells). Prior to the stress, these cultures contained basal cells and supporting
cells but not neurons. After the stress, some cells differentiated into bipolar
neurons expressing a number of neuronal proteins including olfactory marker
protein. Bromodeoxyuridine experiments show that the differentiated neurons arose
from recently divided cells which did not divide again before differentiating. We
conclude that stress disrupts cell surface contacts to induce the immediate
neuronal precursors to undergo final differentiation into olfactory sensory
neurons. This may be a mechanism for enhanced neurogenesis after epithelial
damage.
PMID- 10197777
TI - Tat, a human immunodeficiency virus-1-derived protein, augments excitotoxic
hippocampal injury in neonatal rats.
AB - To test the hypothesis that the human immunodeficiency virus-1-derived Tat
protein may cause neuronal damage in the CNS, we evaluated the neurotoxicity of
recombinant human immunodeficiency virus-1-derived Tat in vivo in seven-day-old
rats. The intrinsic neurotoxicity of Tat (250 ng-1 microg) and the effects of
direct intra-hippocampal co-infusion of Tat with N-methyl-D-aspartate were
assessed. Extent of injury in the lesioned hippocampus was evaluated five days
later, based on histopathology and morphometric measurements of hippocampal
volume. To confirm that any observed neurotoxic effects were attributable to Tat
bioactivity, all experiments included controls that received equal amounts of
heat-treated (boiled) Tat. Intra-hippocampal injection of Tat, alone, elicited
minimal focal tissue damage immediately adjacent to the injection track, and no
hippocampal atrophy. Co-injection of Tat (500 ng) with N-methyl-D-aspartate (5
nmol, threshold excitotoxic dose) doubled the severity of hippocampal injury,
quantified by comparison of bilateral hippocampal volumes, in comparison with
animals that received heat-treated Tat or saline co-injections; in animals that
received injections of N-methyl-D-aspartate (5 nmol) in combination with saline,
heat-treated Tat, or Tat [mean(+/-S.E.M.) % volume loss values in the lesioned
hippocampus were: 11(+/-3), 11(+/-3), and 26(+/-3), respectively (P<0.002,
ANOVA)]. Co-injection of 100 ng Tat with 5 nmol N-methyl-D-aspartate exacerbated
the severity of excitotoxic injury to a similar extent, whereas co-injection of
20 ng Tat had no effect on N-methyl-D-aspartate-mediated injury. Treatment with
the N-methyl-D-aspartate antagonist 3-((RS)-2-carboxypiperazin4-yl)-propyl-1
phosphonic acid (20 mg/kg) markedly attenuated hippocampal injury resulting from
co-injection of 100 ng Tat with N-methyl-D-aspartate [mean(+/-S.E.M.) % volume
loss in lesioned hippocampus: 0.1(+/-2) in 3-((RS)-2-carboxypiperazin-4-yl)
propyl-1-phosphonic acid-treated vs 19(+/-3) in controls, P<0.001, ANOVA]. Co
injection of Tat had no effect on N-methyl-D-aspartate-mediated striatal damage
or on alpha-amino-3-hydroxy-5-methylisoxazole-4-pro hippocampal damage. These
data support the hypothesis that locally released Tat could exert neurotoxic
effects, mediated by N-methyl-D-aspartate receptor activation, in vivo in the
immature brain.
PMID- 10197778
TI - Expression of c-fos, junB, c-jun, MKP-1 and hsp72 following traumatic neocortical
lesions in rats--relation to spreading depression.
AB - The effects of a traumatic neocortical lesion on c-fos, junB, c-jun, MKP-1 and
hsp72 expression were examined by in situ hybridization and immunocytochemistry 1
6 h following transcranial cold injury. The direct current potential was recorded
in the injury-remote cortex to evaluate the role of transient direct current
shifts, i.e. spreading depressions, in gene expression. In 14 out of 21 injured
rats, spreading depression-like depolarizations of the direct current potential
were noticed, which were accompanied by a transient decrease in
electroencephalographic activity and increase in laser Doppler flow. In seven
injured animals, no spontaneous spreading depressions were seen. In animals
without spreading depressions, only a short-lasting response of c-fos, junB, c
jun and MKP-1 messenger RNAs as well as c-Fos protein was bilaterally found in
the piriform cortex, and--with ipsilateral dominance--the dentate gyrus and
hippocampal CA3/4 fields at 1 h after lesioning. In injured animals with
spreading depressions however, a strong elevation was seen in layers II-IV and VI
of the injury-remote ipsilateral cerebral cortex, which persisted over as long as
6 h. Messenger RNA levels for c-fos, junB and MKP-1 were closely related to the
time interval between the last depolarization and the end of experiment. Levels
were highest shortly after transient direct current shifts, and decreased
thereafter mono-exponentially with half-lives of 48, 75 and 58 min for c-fos,
junB and MKP-1 messenger RNAs, respectively. In 6 h animals with spreading
depressions, hsp72 messenger RNA was slightly elevated in layer II of the injury
remote cortex, but heat shock protein 72 was not increased. The present results
demonstrate that spreading depression is the most prominent factor influencing
the trauma-related gene response in the lesion-remote cortical tissue.
PMID- 10197779
TI - Prefrontocortical dopamine depletion induces antidepressant-like effects in rats
and alters the profile of desipramine during Porsolt's test.
AB - The objective of this study was to investigate whether bilateral dopamine
depletion within the medial prefrontal cortex affects depression state, as well
as the antidepressant efficacy of desipramine, in the forced swimming test. The
rat's behaviour was evaluated by quantifying duration of immobility, climbing,
swimming and diving. Immobility latency was also quantified and proved to be a
suitable novel parameter. Monoamine levels within the medial prefrontal cortex
were measured by high-performance liquid chromatography during Porsolt's test, as
well as one week after it. While Porsolt's test was followed by a typical
depression-like profile in sham rats, depletion of prefrontocortical dopamine
(86% vs sham controls) reduced immobility and enhanced swimming, which is
consistent with a diminished depression tonus. The observed enhancement of
swimming was correlated with a high prefrontocortical serotonergic
neurotransmission. On the other hand, desipramine induced antidepression-like
effects in sham rats by increasing prefrontocortical noradrenaline and serotonin
neurotransmisson, but also by blocking the normal increase in dopamine activity
during the swimming test. Interestingly, desipramine behaved in a quite different
manner in lesioned rats. Thus, immobility duration was not further reduced and
only climbing, but not swimming, was enhanced. These effects were correlated with
a preferential enhancement of noradrenaline neurotransmission. In conclusion, the
results indicate that: (i) dopamine neurotransmission within the medial
prefrontal cortex is a factor involved in depression, since dopamine reduction
led to a low depression tonus; (ii) desipramine induces antidepression not only
by enhancing prefrontocortical noradrenaline and serotonin neurotransmission, but
also by blocking the normal increase in dopamine neurotransmission during a
depressant situation; (iii) a selective enhancement of prefrontocortical
serotonin neurotransmission mediates swimming; and (iv) a selectively augmented
prefrontocortical noradrenaline activity mediates climbing during Porsolt's test.
PMID- 10197780
TI - Biochemical and anatomical characterization of forepaw adjusting steps in rat
models of Parkinson's disease: studies on medial forebrain bundle and striatal
lesions.
AB - Deficits in forepaw adjusting steps in rats have been proposed as a non-drug
induced model of the akinesia associated with Parkinson's disease. The present
study examined the relationship between contralateral forepaw adjusting steps and
dopamine depletion after medial forebrain bundle lesions with 6-hydroxydopamine.
Depletion of striatal dopamine by >80% resulted in dramatic reductions in the
ability of rats to make adjusting steps, but rats with < 80% dopamine depletion
had no detectable deficit. The deficit in forepaw adjusting steps was evident by
three days after lesions and did not recover for up to 13 weeks. Compared to
apomorphine-induced rotation, the deficit in adjusting steps was evident at
milder dopamine depletion. Discrete striatal lesions were also utilized to
localize the striatal subregions that mediate forepaw adjusting steps. Forepaw
adjusting steps were reduced after lesions of dorsolateral, ventrolateral or
ventrocentral striatum, but not after lesions of dorsomedial, dorsocentral or
ventromedial striatum. The reductions in adjusting steps after the discrete
striatal lesions were not as severe as after medial forebrain bundle lesions.
Furthermore, none of the discrete striatal lesions resulted in rotation after
apomorphine administration, although a few resulted in increase in amphetamine
induced rotation. Administration of L-3,4-dihydroxyphenylalanine partially
reversed the reductions of forepaw adjusting steps in both sets of lesion
experiments. Together, these results suggest that forepaw adjusting step deficits
in the rat provide a good model for the akinesia of Parkinson's disease both in
medial forebrain bundle and striatal lesions, and would be a useful tool for
investigating the efficacy of various therapeutic strategies.
PMID- 10197781
TI - Neuronal activity in rat red nucleus during forelimb reach-to-grasp movements.
AB - The activity of 259 task-related red nucleus neurons was recorded using chronic
electrophysiological methods in free moving rats. Modulations in activity were
analysed in relation to onset (first detected wrist movement) and end (arrival of
the paw over the food) of a reach-to-grasp movement. Excitatory peaks were found
to begin before, during and after the reach, but there were clear peaks in the
distribution of onset times after reach-onset and before reach-end, reflecting
the fact that one third of all peaks began specifically during the reach,
although this occupied only a small fraction of the analysis time. Both
excitations and inhibitions showed a strong tendency to end in close temporal
association with reach-end. Analysis of excitatory modulation amplitudes showed
that the largest peaks were formed when data was aligned to reach-end, and that
these largest peaks nearly all began during the reach and ended precisely at the
time the paw would have been about to grasp the food. The spread of neural
activation onset times throughout the course of the complex reach-to-grasp
movement is consistent with a relationship of individual neurons in the rat red
nucleus with movements of all parts of the forelimb, as would be expected if all
limb muscle groups are represented in the nucleus. On the other hand the
disproportionate number of modulations that occur during the reach and their
strong alignment with time of reach-end suggests there is a bias in red nucleus
function towards the control of distal motions associated with accurate grasp,
consistent with the result of recent lesion studies. This provides indirect
evidence that functionally the rat red nucleus may be organized in a similar way
to that of monkeys, in which an important role in control of accurate distal
movements is well established. The possibility is discussed that red nucleus
offers a timing signal for co-ordination of movements across joints, in
particular the precise distal-proximal binding normally seen in accurate reach-to
grasp movements.
PMID- 10197782
TI - Independence of motor unit recruitment and rate modulation during precision force
control.
AB - The vertebrate motor system chiefly employs motor unit recruitment and rate
coding to modulate muscle force output. In this paper, we studied how the
recruitment of new motor units altered the firing rate of already-active motor
units during precision force production in the first dorsal interosseous muscle.
Six healthy adults performed linearly increasing isometric voluntary contractions
while motor unit activity and force output were recorded. After motor unit
discharges were identified, motor unit firing rates were calculated before and
after the instances of new motor unit recruitment. Three procedures were applied
to compute motor unit firing rate, including the mean of a fixed number of inter
spike intervals and the constant width weighted Hanning window filter method, as
well as a modified boxcar technique. In contrast to previous reports, the
analysis of the firing rates of over 200 motor units revealed that reduction of
the active firing rates was not a common mechanism used to accommodate the twitch
force produced by the recruitment of a new motor unit. Similarly, during de
recruitment there was no tendency for motor unit firing rates to increase
immediately following the cessation of activity in other motor units.
Considerable consistency in recruitment behavior was observed during repeated
contractions. However, firing rates during repeated contractions demonstrated
considerably more fluctuation. It is concluded that the neuromuscular system does
not use short-term preferential motor unit disfacilitation to effect precise
regulation of muscular force output.
PMID- 10197783
TI - SCO-spondin is evolutionarily conserved in the central nervous system of the
chordate phylum.
AB - Bovine SCO-spondin was shown to be a brain-secreted glycoprotein specifically
expressed in the subcommissural organ, an ependymal differentiation located in
the roof of the Sylvian aqueduct. Also, SCO-spondin makes part of Reissner's
fiber, a phylogenetically and ontogenetically conserved structure present in the
central canal of the spinal cord of chordates. This secretion is a large
multidomain protein probably involved in axonal growth and/or guidance. As
Reissner's fiber is highly conserved in the chordate central nervous system, we
sought genes orthologous to the bovine SCO-spondin gene by Southern blot analysis
in several members of the chordate phylum: urochordates, cephalochordates,
cyclostomes, and lower and higher vertebrates, including humans. In addition,
conserved glycoproteins present in the subcommissural organ and Reissner's fiber
were revealed by immunohistochemistry using antibodies raised against bovine
Reissner's fiber. Variation in the sites of Reissner's fiber production according
to chordate subphylum, presence of this structure in the spinal cord, and
conservation of the SCO-spondin gene are discussed in the context of chordate
central nervous system development. These results indicate that SCO-spondin is an
ancient ependymal secretion, making part of Reissner's fiber, that may have had
an important function during the evolution of the central nervous system in
chordates, including that of the spinal cord.
PMID- 10197784
TI - The upregulation of TNF alpha production is not a generalised phenomenon in the
elderly between their sixth and seventh decades of life.
AB - The aim of this paper was to analyse the link between the intensity of tumor
necrosis factor alpha (TNF alpha) production and the health status of the elderly
and to find out whether the age between sixty and seventy is a 'turning point'
for the changes in the production of this cytokine. Fifty elderly volunteers (age
range: 60-70), twenty-five middle-aged (age range: 36-59) and fifty young (age
range: 20-35) were enrolled into the study. Their health status was graded as
'healthy' and 'almost-healthy'. The level of TNF alpha was determined by
bioassay, the activity of the TNF alpha gene was analysed in non-stimulated PBMC
by the RT-PCR method. The results showed that the production of TNF alpha in the
'healthy' elderly people is not upregulated until the age of sixty-seventy. The
'almost-healthy' elderly are characterised by a higher release of TNF alpha from
the cultures of non- and stimulated PBMC and an activation of the TNF alpha gene
in the non-stimulated PBMC. Summarising, our results indicate that the
deterioration of health status is a prerequisite for an exaggerated TNF alpha
production by peripheral blood mononuclear cells of people between the sixth and
seventh decades of life.
PMID- 10197785
TI - Ability of human plasma to protect against ionising radiation is inversely
correlated with age.
AB - Human blood plasma from persons 30-80 years of age have been measured by a total
antioxidant assay using a highly fluorescent molecule, beta-phycoerythrin (BPE),
as the target for radiation-generated free radicals. The plasma samples showed an
inverse relationship between radioprotective ability and donor age. The results
are consistent with data showing that protein from older subjects provides less
protection against oxidative stress than that from middle-aged subjects.
PMID- 10197786
TI - Accelerated elimination from the circulation of homologous aged red blood cells
in rats bearing anti-spectrin antibodies.
AB - In order to analyse a possible role of anti-spectrin antibodies in the clearance
of aged red blood cells (RBC), a homologous system was employed, whereby a
population of aged RBC, obtained by hypertransfusion, was injected into rats
bearing a high level of anti-spectrin antibodies, following immunization with
spectrin. The aged RBC bound the anti-spectrin antibodies 'in vitro' and were
eliminated from circulation in spectrin-treated rats at a faster rate than in
control rats with naturally occurring antibodies. The analysis of the clearance
curves revealed aged RBC of heterogeneous lifespans: two principal populations of
short- and longer-living could be identified. In rats with anti-spectrin
antibodies, the survival of the short-living population was further reduced.
However, the similar kinetics of elimination of aged RBC in the two groups (with
naturally-occurring and induced antibodies, respectively) suggest that anti
spectrin antibodies strengthened the intervention of the naturally-occurring
ones. On the basis of these results, we assume that during their aging in
circulation, RBC can accumulate surface alterations to make spectrin accessible
to antibodies so that, in addition to anti-band 3 antibodies, anti-spectrin
antibodies may contribute to their elimination.
PMID- 10197787
TI - Effect of aging on intestinal ischemia and reperfusion injury.
AB - Intestinal ischemia/reperfusion (I/R) is a serious disorder that is prevalent in
elderly patients. Reactive oxygen species are implicated in the pathogenesis of
intestinal I/R injury. Reactive oxygen species are also implicated in cellular
senescence and aging. To test the hypothesis that aging exacerbates intestinal
I/R injury, the effects of intestinal I/R on tissue injury were compared between
young (3 month old) and aged (12 month old) mice. Intestinal ischemia was induced
by occluding the superior mesenteric artery with a microbulldog clamp.
Reperfusion was initiated by removing the clamp. Mortality due to intestinal
ischemia followed by reperfusion was significantly higher in aged mice. There
were no differences in the baseline levels of malondialdehyde or myeloperoxidase
activity (indicators of lipid peroxidation and neutrophil infiltration,
respectively) between young and aged mice. Although intestinal I/R caused a
significant increase in malondialdehyde levels and myeloperoxidase activity in
aged mice, similar increases were also observed in young mice. There were no
significant differences in the activities of antioxidant enzymes including
superoxide dismutase, glutathione peroxidase and catalase between young and aged
mice that underwent sham operation. Intestinal I/R caused a significant decrease
in catalase activity only in aged mice. In conclusion, our results indicate that
aged mice are more susceptible to mortality due to intestinal I/R and that an age
dependent decrease in catalase activity may contribute to the observed mortality.
PMID- 10197788
TI - Reconsideration of senescence, immortalization and telomere maintenance of
Epstein-Barr virus-transformed human B-lymphoblastoid cell lines.
AB - We review recent data on senescence and immortalization of human B-lymphoblastoid
cell lines (LCLs) transformed by the Epstein-Barr virus (EBV). Although EBV
transformed LCLs are generally believed to be immortalized, a series of recent
studies, including ours, provided strong evidence that they are mostly mortal and
have non-malignant properties, except for a small proportion of LCLs that are
immortalized by developing a strong telomerase activity. A large proportion of
mortal LCLs have exceptionally long lifespans. Some of them have a lifespan over
150 population-doubling levels, keeping a relatively constant telomere length in
spite of the absence of a detectable telomerase activity, suggesting that they
maintain telomeres by a pathway other than that using telomerase. Here we propose
a model of an alternative pathway to maintain telomeres of such long-lived mortal
LCLs by exploiting extra-chromosomal telomere repeat DNA, which was recently
found by us.
PMID- 10197789
TI - Fluorescence in situ hybridization analysis of the fos/jun ratio in the ageing
brain.
AB - We have examined the expression of the fos and jun genes in the cerebellum of the
rat brain during ageing, by use of a semi-quantitative fluorescence in situ
hybridization (FISH) method. In these experiments we have utilised the digital
imaging capabilities of a cooled CCD camera system to store the fluorescence
intensities of individual cells and to compare the data from each target (fos or
jun) gene with that of a control (beta-actin) gene. In this way we have been able
to obtain a relative quantitation of fos and jun mRNA levels. Purkinje cells were
analysed in brain from Sprague-Dawley rats of 6, 13 and 23 months of age. Data
obtained in this way demonstrated that the level of fos expression decreased
significantly during ageing but, in contrast, that of jun increased between 6 and
13 months and thereafter remained constant. We subsequently carried out a further
comparison of fos/jun ratios in purkinje cells in Wistar rats and also observed a
highly significant fall in the ratio between 6 and 23 months. This change in the
fos/jun ratio has important implications for the composition of the AP-1
transcription factor and for the expression of genes that it regulates.
PMID- 10197791
TI - Age-induced changes in the enteric nervous system in the mouse.
AB - The enteric nervous system of the murine gut was investigated by
immunocytochemistry in 1-, 3-, 12- and 24-month-old mice, using protein gene
product 9.5, a general marker for nerve elements. Myenteric and submucosal plexi
were quantified by computerized image analysis. In antrum, there were
significantly fewer neurones per ganglion in both myenteric and submucosal
ganglia of 12- and 24-month-old mice than in 3-month-old animals. The same was
true of duodenum and colon. The relative volume density of nerve fibres in antral
muscularis propria was significantly greater in the 1-, 12- and 24-month-old mice
than in the 3-month-old mice. In colon, there were fewer submucosal ganglia per
millimetre baseline in 1-month-old mice than in 3-month-old mice. The colonic
myenteric ganglion in 1-, 12- and 24-month-old mice was smaller than in 3-month
old mice. There was no statistical difference between females and males regarding
the number of ganglia per millimetre baseline, ganglionic area, number of
neurones per ganglion or the relative volume density of nerve fibres in either
the myenteric or submucosal plexi. As the enteric nervous system is responsible
for coordinating and integrating the motility of the gut, the ageing-related
changes reported here may well be of some relevance for the increased
gastrointestinal motility dysfunction in the elderly persons.
PMID- 10197790
TI - Effects of dietary taurine supplementation or deprivation in aged male Fischer
344 rats.
AB - Taurine is a sulfur amino acid that is present in high concentration in mammalian
tissues and previously has been reported to decline in a number of tissues with
advancing age. The aims of the present study were to examine: (1) the effects of
dietary taurine supplementation; (2) the effects of taurine-free diets; (3) the
ability of aged rats to conserve urinary taurine; and (4) the consequences of
these dietary manipulations on some biochemical parameters. Male F344 rats (n =
30/group) 18 months of age were placed on control diets, diets supplemented with
1.5% taurine in the drinking water, or a taurine-free diet for 10 months. An
adult control group (12 months old at the end of the study) on normal diets was
included for comparison purposes. Significant (P < 0.05) age-related declines in
taurine content were observed in the spleen, kidney, eye, cerebellum and serum.
Taurine supplementation corrected these deficits in tissue content in aged rats
and in many cases increased taurine content above that of adult controls. Urinary
excretion of taurine was significantly (P < 0.05) reduced in aged rats indicating
an increased need to conserve taurine. Taurine-deficient diets did not further
exacerbate the age-related decline in tissue taurine content, suggesting
biosynthetic adaptations to the lack of dietary taurine. Dietary taurine
supplementation blunted age-related declines in serum IGF-1 and increases in
serum creatinine and blood urinary nitrogen (BUN). These studies suggest that
advanced aging results in a taurine-deficient state that can be corrected by
dietary supplementation.
PMID- 10197792
TI - Age-related attenuation in the expression of the major heat shock proteins in
human peripheral lymphocytes.
AB - A defining characteristic of human ageing is the reduced ability to maintain
homeostasis in the face of adverse environmental stresses. This progressive
impairment may be a major cause for the increased incidence of infections, and
general morbidity and mortality in the elderly. Heat shock proteins (hsps) or
stress proteins, induced in response to hyperthermia and to various other
physical, chemical and biological stressors, are often also expressed
constitutively at a lower level and perform many essential functions in the cell.
Here we investigate age-related changes in the heat induced expression of a
comprehensive range of hsps at the translational level using primary human
peripheral lymphocytes in short term culture. Our study reveals age-related
attenuation in the response of the well characterised up-regulated molecular
chaperone system hsp 70, the steroid-receptor binding hsp 90 and the chaperonin
hsp 60. A diminution with age is also demonstrated in the heat induced response
of hsps 105, 56, 47, 40, 27, and 16. Differentially down-regulated proteins at
100, 38, and 18 kDa were also noted.
PMID- 10197793
TI - Fludarabine-based non-myeloablative chemotherapy followed by infusion of HLA
identical stem cells for relapsed leukaemia and lymphoma.
AB - Many patients have not been offered potentially curative allogeneic marrow
transplants because of the toxicity of myeloablative regimens in the setting of
advanced age or organ dysfunction. We treated five patients, ineligible for
myeloablative chemotherapy due to one of these criteria, with fludarabine-based
non-myeloablative chemotherapy followed by reinfusion of G-CSF-mobilised
allogeneic peripheral blood progenitor cells (PBPC). Two patients died early of
multi-organ failure. Another patient with massive splenomegaly was infused with a
suboptimal number of PBPC; no engraftment was documented. The remaining two
patients demonstrated mixed chimerism early post-transplant, but by 3 and 6
months respectively, engraftment was almost entirely of donor origin. One of
these patients, transplanted with relapsed AML, remains in remission with
extensive chronic GVHD at 17 months. The other patient, transplanted with
chemorefractory mantle cell lymphoma, progressed early post-transplant but
entered remission coincident with the onset of severe GVHD following cessation of
cyclosporin A, suggesting a powerful graft-versus-mantle cell lymphoma effect.
These preliminary observations suggest this approach results in engraftment and
GVHD/graft-versus-tumour effects similar to myeloablative regimens and may
provide an alternative in patients ineligible for conventional conditioning
regimens.
PMID- 10197794
TI - Superior autologous blood stem cell mobilization from dose-intensive
cyclophosphamide, etoposide, cisplatin plus G-CSF than from less intensive
chemotherapy regimens.
AB - The study purpose was to determine if G-CSF plus dose-intensive cyclophosphamide
5.25 g/m2, etoposide 1.05 g/m2 and cisplatin 105 mg/m2 (DICEP) results in
superior autologous blood stem cell mobilization (BSCM) than less intensive
chemotherapy. From January 1993 until May 1997, 152 consecutive patients with non
Hodgkin's lymphoma (n = 55), breast cancer (n = 47), Hodgkin's disease (n = 14),
multiple myeloma (n = 9), AML (n = 9), or other cancers (n = 18) initially
underwent BSCM by one of three methods: Group 1: G-CSF alone x 4 days (n = 30).
Group 2: disease-oriented chemotherapy, dosed to avoid blood transfusions,
followed by G-CSF starting day 7 or 8, and apheresis day 13 or 14 (n = 82). Group
3: DICEP days 1-3, G-CSF starting day 14, and apheresis planned day 19, 20 or 21
(n = 40). A multivariate analysis was performed to determine which factors
independently predicted BSCM. The median peripheral blood CD34+ (PB CD34+) cell
count the morning of apheresis linearly correlated with the number of CD34+ cells
removed per litre of apheresis that day. The median PB CD34+ cell count and
median CD34+ cells x 10(6) removed per litre of apheresis were highest for Group
3, intermediate for Group 2, and lowest for Group 1. By multivariate analysis,
mobilization group (3 > 2 > 1), disease other than AML, no prior melphalan or
mitomycin-C, and less than two prior chemotherapy regimens predicted better BSCM.
Out of 15 Group 3 patients who had infiltrated marrows, 11 had no detectable
cancer in marrow and apheresis products after DICEP. These data suggest that
DICEP results in superior BSCM than less intensive chemotherapy regimens.
PMID- 10197795
TI - Administration of G-CSF to normal individuals diminishes L-selectin+ T cells in
the peripheral blood that respond better to alloantigen stimulation than L
selectin- T cells.
AB - To determine whether administration of G-CSF induces phenotypic or functional
changes in T cells, we examined peripheral blood T cells from normal individuals
receiving G-CSF for activation antigen and adhesion molecule expression before
and after G-CSF administration. G-CSF (10 microg/kg/day) was administered
subcutaneously to 14 normal individuals for 3-5 days and their PBMC were serially
analyzed with monoclonal Ab (mAb) directed to HLA-DR, CD45RO, CD45RA, CD25,
CD122, CD95, CD11a, CD49d, CD44 and CD62L (L-selectin) coupled with anti-CD3 mAb.
Among T cells positive for these antigens, only the proportion of T cells
expressing L-selectin significantly decreased from 68% to 37% after 3-day G-CSF
administration. When peripheral blood CD3+ T cells obtained before and after G
CSF administration were sorted into two populations depending on the expression
of L-selectin and tested for their proliferative response to allogeneic B cells,
the reactivity of L-selectin- cells to alloantigen stimulation was consistently
lower than that of L-selectin+ cells regardless of the exposure to G-CSF. The
decrease in the relative number of L-selectin+ cells induced by G-CSF
administration may contribute to the unexpectedly low incidence of severe acute
GVHD after allogeneic PBSC transplantation.
PMID- 10197796
TI - Stem cell mobilization with G-CSF alone in breast cancer patients: higher
progenitor cell yield by delivering divided doses (2 x 5 microg/kg) compared to a
single dose (1 x 10 microg/kg).
AB - We investigated the schedule dependency of G-CSF (10 microg/kg) alone in
mobilizing peripheral blood progenitor cells (PBPC) in breast cancer patients.
After a median of three cycles (range, 2-6) of anthracycline-based chemotherapy,
49 patients with breast cancer (stage II/III, > or = 10+ Ln n = 36; locally
advanced/inflammatory n = 8, stage IV (NED) n = 5) underwent PBPC collection
after steady-state mobilization either with 1 x 10 microg/kg (n = 27) or with 2 x
5 microg/kg (n = 22) G-CSF daily for 4 consecutive days until completion of
apheresis. Apheresis was started on day 5. Priming with 2 x 5 microg/kg resulted
in a higher median number of CD34+ cells (5.8 vs 1.9 x 10(6)/kg, P = 0.003), MNC
(6.6 vs 2.6 x 10(8)/kg, P < 0.001) and CFU-GM (6.5 vs 1.3 x 10(4)/kg, P = 0.001)
in the first apheresis than with 1 x 10 microg/kg. Also the overall number of
collected BFU-E was higher in the 2 x 5 microg group (9.2 vs 3.1 x 10(4)/kg; P =
0.01). After high-dose chemotherapy with cyclophosphamide/thiotepa/mitoxantrone
(n = 46) hematopoietic engraftment with leukocyte count > 1.0/nl was reached in
both groups after a median of 10 days (range, 8-15) and with platelets count >
50/nl after 12 (range, 9-40) and 13 days (range, 12-41), respectively. A
threshold of > 2.5 x 10(6)/kg reinfused CD34+ cells ensured rapid platelet
engraftment (12 vs 17 days; P = 0.12). Therefore, the target of collecting > 2.5
x 10(6) CD34+ cells was achieved in 21/27 (80%) patients of the 1 x 10 microg
group and in 21/22 (95%) patients of the 2 x 5 microg/kg group with a median of
two aphereses (range, 1-4). None in the 10 microg/kg group, but 6/22 (28%)
patients in the 2 x 5 microg/kg group required only one apheresis procedure,
resulting in fewer apheresis procedures in the 2 x 5 microg/kg group (mean, 1.8
vs 2.3, P = 0.01). These results demonstrate that priming with 10 microg/kg G-CSF
alone is well tolerated and effective in mobilizing sufficient numbers of CD34+
cells in breast cancer patients and provide prompt engraftment after CTM high
dose chemotherapy. G-CSF given 5 microg/kg twice daily (2 x 5 microg) leads to a
higher harvest of CD34+ cells and required fewer apheresis procedures than when
given 10 microg/kg once daily (1 x 10 microg).
PMID- 10197797
TI - Optimal timing for processing and cryopreservation of umbilical cord
haematopoietic stem cells for clinical transplantation.
AB - Some of the factors that may influence the number and quality of cord blood
haematopoietic progenitor cells available for transplantation have been
investigated including site of collection, delayed processing after collection
and cryopreservation protocol. We used the granulocyte-macrophage progenitor (CFU
GM) and erythroid burst-forming unit (BFU-E) assays to quantify progenitors. The
capacity of CFU-GM to produce secondary colonies was used as a measure of
progenitor cell quality. We found that: (1) there were no significant differences
in total nucleated cells (TNC), mononuclear cells (MNC), CFU-GM or BFU-E numbers
in paired specimens from the umbilical vein or veins at the base of the placenta.
The potential of the CFU-GM to produce secondary colonies from the two sites was
similar; (2) storing cord blood at room temperature or at 4 degrees C resulted in
a significant reduction in progenitor cell numbers beyond 9 h; and (3)
cryopreservation following either controlled rate freezing or passive cooling
reduced MNC numbers, viability and CFU-GM survival insignificantly but the
potential of CFU-GM to produce secondary colonies was significantly reduced post
cryopreservation (P = 0.04). We conclude that the yield of CB progenitor cells is
not affected by the site of collection, but is adversely affected by delays
between collection and cryopreservation. Furthermore, cryopreservation reduced
the CFU-GM potential to produce secondary colonies. Measures of progenitor cell
quality as well as quantity may be relevant to assessing CB blood collections.
PMID- 10197798
TI - Prevention of graft-versus-host disease (GVHD) by elimination of recipient
reactive donor T cells with recombinant toxins that target the interleukin 2 (IL
2) receptor.
AB - Graft-versus-host disease (GVHD), due to the presence of recipient-reactive T
cells, limits the usefulness of bone marrow transplantation (BMT) and is a major
contributor to patient mortality. To prevent GVHD, murine and human T cells were
activated by antigen or mitogens and treated with a genetically engineered form
of Pseudomonas exotoxin A (PE) directed against the IL-2 receptor. Treatment with
the chimeric toxin eliminated alloreactive cytotoxic T lymphocytes (CTL) as
determined by cytotoxicity and mixed lymphocyte culture assays. Precursor
frequencies of alloreactive cytotoxic T cells and proliferative T cells were
reduced up to 100-fold as shown by limiting dilution assays. Flow cytometric
analyses revealed that treatment with the chimeric toxin completely eliminated
CD25+ cells from the cultures. Toxin treatment had no significant effect on
hematopoietic stem and progenitor cells as determined in vitro by colony-forming
assays and in vivo by long-term hematopoietic recovery after 950 rad irradiation.
Toxin treatment decreased GVHD in transplanted mice to less than 10% (as compared
to 88% in untreated controls). Thus, it is possible to prevent life-threatening
GVHD after BMT by using a CD25 receptor-directed toxin to eliminate host-reactive
T cells from bone marrow grafts.
PMID- 10197799
TI - Impact of cyclosporine and methylprednisolone dose used for prophylaxis and
therapy of graft-versus-host disease on survival and relapse after allogeneic
bone marrow transplantation.
AB - In order to determine whether doses of cyclosporine and methylprednisolone used
for prophylaxis and therapy of acute graft-versus-host disease (GVHD) have any
influence on relapse and survival following allogeneic bone marrow
transplantation (BMT), we studied 176 adult patients with hematologic
malignancies, who underwent a first allogeneic transplant from an HLA-identical
sibling donor. Two methods of management of acute GVHD used in two different
centers were compared: group I included 62 patients who had 'standard' management
of GVHD including prophylaxis with 1-3 mg/kg/day of cyclosporine and treatment
with 2 mg/kg/day of methylprednisolone when acute GVHD developed; group II
included 114 patients who received 'intensive' management of GVHD including
prophylaxis with 5 mg/kg/day of cyclosporine and treatment with high-dose
methylprednisolone (8-20 mg/kg/day for 3 days) at the onset of GVHD. The overall
incidence of GVHD was the same in both groups. However, acute GVHD was more
severe in group I than in group II (P < 0.0001), with consequently less
resolution of GVHD after treatment in group I (61%) than in group II (80%) (P =
0.06). Overall survival and disease-free survival (DFS) did not differ between
the two groups. However, actuarial risk of disease relapse was significantly
higher in group II than in group I (36% vs 17%, P = 0.02). In a multivariate
analysis taking into account known factors influencing GVHD and relapse, only
type of GVHD management and age were significantly predictive for the occurrence
of GVHD, while only type of GVHD management and pathology other than chronic
myeloid leukemia (CML) were predictive for relapse. This study demonstrates that
intensity of GVHD prophylaxis and therapy can influence the graft-versus-leukemia
effect by decreasing severity of GVHD but at the price of increasing relapse rate
post transplant.
PMID- 10197800
TI - Treatment of acute graft-versus-host disease with PUVA (psoralen and ultraviolet
irradiation): results of a pilot study.
AB - Acute graft-versus-host disease (aGVHD) is a frequent and major complication
after allogeneic stem cell transplantation. For many years psoralen and
ultraviolet (UV)-A light have been used in the treatment of chronic cutaneous
graft-versus-host disease, but few patients have received PUVA therapy for aGVHD.
We assessed 20 patients who received PUVA therapy for acute cutaneous GVHD (grade
2-4). Seven patients showed additional organ manifestations (liver, gut). To
better quantify the cutaneous lesions, a new scoring system was introduced:
intensity of erythema (0-3) x %body surface + size of bullae (4-5) x %body
surface affected. All patients received prednisolone and PUVA for treatment of
aGVHD. Fifteen patients (75%), 12 with manifestations restricted to the skin,
responded by score classification (average time to a 50% score reduction: 39
days) and reduction of the dosage of prednisolone (average time to a 50%
prednisolone reduction: 35 days). PUVA treatment was well tolerated and might
play a role in the therapy of acute cutaneous GVHD.
PMID- 10197801
TI - The cytotoxicity of mafosfamide on G-CSF mobilized hematopoietic progenitors is
reduced by SH groups of albumin--implications for further purging strategies.
AB - The efficacy of mafosfamide purging depends on factors like incubation time, drug
and erythrocyte concentration. To determine the influence of protein-bound SH
groups in the incubation medium, the cytotoxicity of mafosfamide on G-CSF
mobilized CD34+/- cells was evaluated by short-term culture assays and drug
concentration measurements. 100 micromol/ml mafosfamide was incubated for 30 min
in five buffers (PBS, PBS with 1%, 5% and 10% BSA and plasma). The mean
calculated areas under the concentration-time curves (AUC) were 2489 +/- 198,
1561 +/- 286, 976 +/- 201, 585 +/- 62 and 605 +/- 196 micromol/l/min. The mean
reductions of CFU-GM growth were 79.4%, 73.0%, 62.5%, 30.3%, 6.2% respectively.
Similar results were obtained for BFU-E. Regression analysis showed a good
correlation between cytotoxicity and AUCs (CFU-GM: r = 0.8195; BFU-E: r =
0.8207). This effect is well explained by the different concentrations of SH
moieties in the incubation medium resulting in a higher drug binding capacity.
The profound difference between AUCs and CFU-GMs in plasma and 10% BSA cannot be
explained by the quantity of SH-groups. It is probably due to an additional
enzymatic drug degeneration by the 3'-5'exonuclease subsite of plasma DNA
polymerase. In conclusion, the concentration of albumin-associated SH groups
strongly influences the cytotoxicity of mafosfamide. It has to be considered as a
new and important aspect in ex vivo bone marrow purging.
PMID- 10197802
TI - Liposomal amphotericin (AmBisome) in the prophylaxis of fungal infections in
neutropenic patients: a randomised, double-blind, placebo-controlled study.
AB - Liposomal amphotericin (AmBisome) 2 mg/kg three times weekly was compared with
placebo as prophylaxis against fungal infection in patients undergoing
chemotherapy or bone marrow transplantation (BMT) for haematological
malignancies. Prophylaxis began on day 1 of chemotherapy and continued until
neutrophils regenerated or infection was suspected. Of 161 evaluable patients, 74
received AmBisome and 87 received placebo. Proven fungal infections developed in
no patients on AmBisome and in three on placebo (3.4%) (P = NS). Suspected fungal
infections requiring intervention with systemic antifungal therapy (usually
amphotericin B) occurred in 31 patients on AmBisome (42%) and in 40 on placebo
(46%) (P = NS). Suspected deep-seated infections developed in 21 (28.3%) and 31
(35.6%) patients, respectively (P = NS). Time to develop a suspected or proven
deep-seated infection showed a trend in favour of AmBisome (P = 0.11). Fifty
patients had fungal colonisation (48 with Candida spp, two with Aspergillus spp)
of at least one body site during prophylaxis; 15 patients while receiving
AmBisome (20%) and 35 while on placebo (40%) (P < 0.01). Time to colonisation was
significantly delayed in the group receiving AmBisome (P < 0.05). Treatment
related toxicity was modest and no additional toxicity was observed in patients
receiving AmBisome. AmBisome 2 mg/kg three times weekly is safe and reduces
fungal colonisation in patients receiving intensive chemotherapy or BMT. However,
despite encouraging trends, prophylactic AmBisome did not lead to a significant
reduction in fungal infection or in requirement for systemic antifungal therapy.
PMID- 10197803
TI - Treatment with interleukin-2 (IL-2) and interferon (IFN(alpha 2b)) after
autologous bone marrow or peripheral blood stem cell transplantation in onco
hematological malignancies with a high risk of relapse.
AB - Nine patients with onco-hematological malignancies with a poor prognosis due to
high risk of relapse received immunotherapy with interleukin-2 (IL-2) and
interferon (IFN(alpha 2b)) s.c. as maintenance therapy after receiving autologous
bone marrow or peripheral blood stem cell transplantation (ABMT/PBSCT). All the
patients were considered at very high risk of relapse. We attempted to assess the
efficiency, toxicity and clinical effects of these cytokines in these patients.
Five patients were treated with high-dose of IL-2 and the other four patients
with escalating doses every month. Side-effects in the first group of patients
consisted of fever, chills, weakness, nausea, anorexia, loss of weight and local
dermatitis in the injection site. Toxicity on the WHO scale was grade II in three
patients and grade IV in the other two patients. In the second group of patients,
the same clinical signs of toxicity appeared, but these were grade I on the WHO
scale in all patients. None of the patients had infections or died in relation to
administration of IL-2. Four patients died of relapse or progression of their
hematological malignancies. The other five patients are alive, one in chronic
phase of CML and the other four patients are in complete remission of their
malignancies.
PMID- 10197804
TI - Increases in 4-hydroxynonenal and hexanal in bone marrow of rats subjected to
total body X-ray irradiation: association with antioxidant vitamins.
AB - Radiation-induced lipid peroxidation and its association with antioxidant
vitamins in the bone marrow (BM), of rats subjected to total body irradiation
(TBI) of X-rays at a dose of 3 Gy was investigated. The concentration of vitamin
C in the BM decreased at 4 h, and reached about 2% of the control level at 24 h
after irradiation. The concentration of vitamin E in the BM also decreased to 43%
at 24 h. Corresponding to the decrease in vitamin E concentration, the
concentration of 4-hydroxynonenal (HNE) in the BM increased 2.5-fold at 24 h.
Similarly, increases in the concentrations of hexanal and thiobarbituric acid
reactive substances (TBA-RS) were detected in the BM. In the plasma, these
parameters of lipid peroxidation were unchanged up to 48 h, but were increased at
96 h after irradiation. Four days of vitamin E administration to rats (p.o. 460
mg/kg body weight) prior to the 3 Gy X-irradiation increased the vitamin E
concentration in the BM to 1.3-fold the control level, but did not attenuate the
increases in HNE and hexanal in the BM. The slight accumulation of vitamin E in
the BM as a result of the vitamin E treatment may be partly related to this lack
of vitamin E effect.
PMID- 10197805
TI - Image-guided central venous catheters for apheresis.
AB - Apheresis is an increasingly important procedure in the treatment of a variety of
conditions, sometimes performed via peripheral access because of concern over
major complications associated with central venous catheter (CVC) placement. This
study sought to determine the safety and success for ultrasound and
fluoroscopically guided, non-tunneled dual lumen CVCs placed for apheresis.
Prospective data collection was made of 200 attempted CVC placements in the
radiology department utilizing real time sonographic guidance. The complications
relating to placement were noted in all and the number of passes required for
venepuncture and whether a single wall puncture was achieved was recorded in 185
cases. Duration of catheterization and reason for line removal were recorded in
all. Our study group included 71 donors providing peripheral blood stem cells for
allogeneic transplant. CVCs were successfully placed in all patients, 191 lines
in the internal jugular and seven in the femoral vein. 86.5% required only a
single pass and 80.5% with only anterior wall puncture. Inadvertent but
clinically insignificant arterial puncture occurred in six (3%) cases. In no case
did this prevent line placement. There were no other procedure-related
complications. 173 (87.4%) catheters were removed the same day. No catheters were
removed prematurely. There was one case of prolonged venous bleeding. Our study
demonstrates the safety of central venous catheters for apheresis provided that
duration of catheterization is short and real-time sonographic guidance is used
for the puncture, and guide wire and catheter placement are confirmed
fluoroscopically.
PMID- 10197806
TI - IL-2/LAK therapy for refractory acute monoblastic leukemia relapsing after
unrelated allogeneic bone marrow transplantation.
AB - Leukemia relapse is a major cause of treatment failure after allogeneic bone
marrow transplantation. We administered recombinant interleukin-2 (rIL-2) to a
patient who relapsed after unrelated allogeneic bone marrow transplantation
(uBMT). While the number of peripheral blood monoblastic leukemia cells increased
after administration of rIL-2, the patient achieved durable remission for 5
months after low-dose chemotherapy followed by adoptive transfer of engrafted
graft-derived lymphokine-activated killer (LAK) cells. Following the
disappearance of the blast cells, however, both cutaneous and liver GVHD were
exacerbated. Administration of rIL-2 and adoptive transfer of graft-derived LAK
cells are considered to be possible choices for the treatment of acute leukemia
relapsing after uBMT when donor leukocyte transfusion is not available.
PMID- 10197807
TI - Parentage testing implications of male fertility after allogeneic bone marrow
transplantation.
AB - Fertility is expected to be reduced after the extensive chemotherapy and/or
radiotherapy that is needed for conditioning prior to bone marrow
transplantation. However, a male patient can be fertile, and in very rare
situations such as reported here, this may confuse subsequent paternity testing.
The patient, initially excluded as the biological father by red cell types but
not by HLA, was subsequently included after the history of his previous marrow
transplant was revealed, a review of the HLA results and further RFLP testing on
buccal mucosal cells. This case points to the need for good history taking before
performing paternity testing.
PMID- 10197808
TI - Fatal outcome due to cyclosporine neurotoxicity with associated pathological
findings.
AB - We present a case of death likely to be directly due to cyclosporine (CsA)
neurotoxicity. To date, there have been no reports of deaths directly due to CsA
neurotoxicity, nor has an associated histological lesion been described
independent of confounding processes. A 54-year-old male received an HLA-matched
unrelated BMT for CML. He developed progressive encephalopathy and on day +79 had
a generalized seizure. All CSF studies were negative for infectious causes. MRI
revealed diffuse, symmetrical white matter abnormalities located in the occipital
sub-cortex, thalamus, mid brain, pons, and cerebellum which were typical of CsA
toxicity. The patient died of central respiratory failure within 72 h of
discontinuing CsA. Autopsy revealed diffuse patchy white matter edema and
astrocytic injury without evidence of axonopathy, demyelination, microvascular
injury, or infectious/inflammatory process. This case demonstrates previously
undescribed lethal CsA neurotoxicity and may reveal an associated primary
pathological lesion.
PMID- 10197809
TI - Donor leukocyte infusions inducing remissions repeatedly in a patient with
recurrent multiple myeloma after allogeneic bone marrow transplantation.
AB - We describe a patient with recurrent relapses after allogeneic BMT for multiple
myeloma who repeatedly went into CR after donor leukocyte infusions (DLI). The
first bone marrow relapse, 24 months after allogeneic BMT, was treated
successfully with the infusion of 1.2 x 10(8) donor T cells. The second
extramedullary relapse, 18 months later with a pleural mass and midthoracic spine
process, responded again to DLI, however, only after three courses were given,
each with escalating doses of T cells. The pleural mass was treated successfully
with radiation therapy after the second DLI but reappeared 3 months later and
responded again to the final DLI course with 5 x 10(8) T cells/kg. Nevertheless,
graft-versus-host disease (GVHD) did not occur. Retrospective analysis of minimal
residual disease in bone marrow aspirates during CR periods using a sensitive
quantitative tumor-specific PCR showed that BM tumor cell infiltration persisted.
The possible clinical implications of this case report, like maintenance DLI and
the aim for molecular remissions, are discussed.
PMID- 10197810
TI - Accelerated atherosclerosis in a patient with post-BMT nephropathy.
PMID- 10197811
TI - Detection of maternal cell contamination in human cord blood: which perspectives?
PMID- 10197812
TI - Anaphylactoid reaction to granulocyte colony-stimulating factor used in
mobilization of peripheral blood stem cell.
PMID- 10197813
TI - The human cerebral cortex: gender differences in structure and function.
AB - Most people are aware of subtle differences in cognitive functions between men
and women. Psychometric tests confirm specific gender differences in a number of
areas, the most robust being in spatial orientation and mathematical tasks which
are better performed by males. Nonetheless, normal males and females perform
comparably on intelligence tests and human brains lack sexual dimorphism on
routine neuropathological exams--other than mean differences in weight and size.
Even so, human brains demonstrate: 1) a sexually dimorphic nucleus in the
hypothalamus with twofold neuronal numbers in males than in females; 2) the
planum temporale/anterior Sylvian fissure on the left side are larger in males;
3) some studies reveal the posterior corpus callosum to be more bulbous in
females while others fail to show this difference; and 4) a cytoarchitectural
study demonstrates definite sexual dimorphism of cerebral cortex with
significantly higher neuronal densities and neuronal number estimates in males
and a reciprocal increase in neuropil/neuronal processes in female cortex as
implied by the 2 sexes' similar mean cortical thicknesses. Such morphologic
differences may provide the structural underpinning for the gender differences
exhibited by the normal and diseased brain. Males manifest a higher prevalence of
mental retardation and of learning disabilities than females which may reflect
the male fetus' smaller overproduction of nerve cells. Such an inference is
supported by the demonstration of 1) better functional recovery following early
brain injury than after later insults, 2) substantially overproduced and
secondarily reduced nerve cells in human cerebral cortex during gestation, 3) the
demonstration of a similar neuronal production and a testosterone-dependent
neuronal involution of the sexually dimorphic hypothalamic nucleus in rats, and
4) more cortical neurons present in the adult human male than female. If an
overproduced nerve cell population is capable of compensating for pathologic
nerve cell losses taking place during the process of neuronal involution, the
magnitude of overproduced nerve cells may define the extent of the protection
conveyed. Because male fetuses appear to involute fewer overproduced cortical
neurons than females, this gender difference could explain in part the boys'
greater functional impairments from early brain damage. Women, on the other hand,
exhibit a higher incidence and prevalence of dementia than do men. Given the
females' overall larger extent of cortical neuropil (neuronal processes) and
lower neuronal numbers compared with men, any disease that causes neuronal loss
could be expected to lead to more severe functional deficits in women due to
their loss of more dendritic connections per neuron lost. In conclusion,
superimposed on a strong background of functional and structural equality, human
male and female cerebral cortex display distinct, sexually dimorphic features,
which can begin to be linked to a complex array of gender-specific advantages and
limitations in cognitive functions.
PMID- 10197814
TI - Influence of apolipoprotein E genotype on neuronal damage and apoE
immunoreactivity in human hippocampus following global ischemia.
AB - Apolipoprotein E (apoE) influences the response to and outcome from brain injury
possibly through alterations in neuronal repair mechanisms. This study aimed to
determine alterations in neuronal and glial apoE after brain injury in patients
and sought to determine whether possession of an apoE-epsilon4 allele influences
the degree of apoE immunoreactivity or the degree of neuronal damage following
brain injury. ApoE immunoreactivity and neuronal damage were semiquantitatively
assessed in the temporal lobe of a group of controls (n = 44) and in a group of
patients who had an episode of global ischemia and subsequently died (n = 58,
survival ranged from 1 hour to 3 months). There was a significant degree of
neuronal damage in all hippocampal sectors and in the neocortex of the global
ischemia group compared with controls (p < 0.0001). Glial apoE immunoreactivity
was significantly increased in hippocampal sectors (CA1, CA2, CA3/CA4, dentate
fascia) in the global ischemia group compared with controls (p < 0.01). Neuronal
apoE immunoreactivity was significantly increased in all hippocampal sectors
(CA1, CA2, CA3/CA4, dentate fascia) and in the neocortex of the global ischemia
group compared with controls (p < 0.0001). There was a significant and positive
association between the degree of neuronal apoE immunoreactivity and the degree
of neuronal damage in the global ischemia cases (r2 = 0.691, p < 0.001) and there
was not an association in the control group. Possession of an apoE-epsilon4
allele did not influence the degree of neuronal or glial apoE immunoreactivity or
the degree of neuronal damage in the global ischemia cases or the controls. The
data indicate apoE is markedly increased in neurons and glia following brain
injury. In this study, apoE genotype did not appear to influence neuronal damage,
glial apoE or intraneuronal apoE following injury
PMID- 10197815
TI - Discordant expression of utrophin and its transcript in human and mouse skeletal
muscles.
AB - In order to determine the mechanisms regulating utrophin expression in human
skeletal muscle, we examined the expression and distribution of utrophin and its
transcript in biopsies from normal subjects as well as from Duchenne muscular
dystrophy (DMD) and polymyositis (PM) patients. We first determined by
immunoblotting that in comparison to biopsies from normal subjects, utrophin
levels were indeed higher in muscle samples from both DMD and PM patients as
previously shown. By contrast, levels of utrophin mRNAs as determined by both RT
PCR assays and in situ hybridization, were identical in muscle samples obtained
from normal subjects versus DMD and PM patients. In these experiments, we also
noted that while utrophin transcripts had a clear tendency to accumulate within
the postsynaptic sarcoplasm of normal human muscle fibers, the extent of synaptic
accumulation was considerably less than that which we recently observed in mouse
muscle fibers. The distribution of utrophin transcripts in synaptic and
extrasynaptic compartments of muscle fibers obtained from DMD and PM patients was
similar to that seen along muscle fibers from normal subjects. Finally, we also
monitored expression of utrophin and its transcripts during regeneration of mouse
muscle induced to degenerate by cardiotoxin injections. In these regenerating
muscles, we observed by both immunoblotting and immunofluorescence, a large
increase (4- to 7-fold) in the levels of utrophin. In agreement with our results
obtained with human muscle, the increase in utrophin levels in regenerating mouse
muscle was not accompanied by parallel changes in the abundance of utrophin
transcripts. Taken together, these results indicate that the levels of utrophin
and its transcript in muscle are discordantly regulated under certain conditions
thereby highlighting the important contribution of post-transcriptional
regulatory mechanisms in the control of utrophin levels in skeletal muscle
fibers.
PMID- 10197816
TI - Cytokine-induced acute inflammation in the brain and spinal cord.
AB - Different compartments in the central nervous system mount distinct inflammatory
responses. The meninges and choroid plexus respond to pro-inflammatory stimuli in
a manner reminiscent of a peripheral inflammatory response, whereas the brain
parenchyma is refractory. Trauma-induced lesions in brain and in spinal cord are
associated with leukocyte infiltration, blood-brain barrier (BBB) breakdown, and
secondary tissue destruction. Unexpectedly, these phenomena are generally more
pronounced in the parenchyma of the spinal cord than in the parenchyma of the
brain. To investigate whether these differences between brain and spinal cord can
be attributed, at least in part, to differing sensitivities to proinflammatory
cytokines, we stereotactically injected recombinant rat (rr) TNFalpha or rrIL
1beta into the striatum or the spinal cord of Wistar rats. In the brain, the
injection of rrTNFalpha failed to evoke BBB breakdown or leukocyte recruitment,
whereas in the spinal cord injection of TNFalpha resulted in marked BBB breakdown
and leukocyte recruitment. Similarly, the injection of rrIL-1beta into the brain
parenchyma failed to induce BBB breakdown and gave rise to only minimal
neutrophil recruitment, whereas the injection of rrIL-1beta into the spinal cord
induced significant BBB breakdown and recruitment of neutrophils and lymphocytes.
Thus, using a minimally invasive injection technique, equivalent in both
circumstances, we have shown that there are marked differences in the
inflammatory response between the brain parenchyma and spinal cord parenchyma.
This observation has important implications for the treatment of spinal cord
injuries.
PMID- 10197817
TI - Reduction in choline acetyltransferase immunoreactivity but not muscarinic-m2
receptor immunoreactivity in the brainstem of SIDS infants.
AB - The cholinergic neurotransmitter system is vital for several brainstem functions
including cardiorespiratory control and central chemosensitivity. This study has
examined aspects of the cholinergic neurotransmitter system in the brainstem of
sudden infant death syndrome (SIDS) and control infants. The cellular
localisation and the optical density of the immunoreactivity of the cholinergic
enzyme choline acetyltransferase (CHAT-IR) and the muscarinic acetylcholine
receptor m2 (m2-IR) in the medulla was described in 14 SIDS and 9 control cases.
There was a reduction in the number of CHAT-IR neurons in the hypoglossal nucleus
(control: 71.2+/-8.3% vs SIDS: 46.1+/-5.3%) and the dorsal motor nucleus of the
vagus (DMV) (control: 77.2+/-5.0% vs SIDS: 52.5+/-7.4%) and reduced optical
density of CHAT-IR in the hypoglossal nucleus (control: 0.20+/-0.01 vs SIDS;
0.14+/-0.02) in SIDS infants. In contrast there were no changes in the optical
density of m2-IR in the hypoglossal nucleus, the DMV, or the arcuate nucleus.
Hypoplasia of the arcuate nucleus was observed in one SIDS infant. These results
suggest that there is a specific defect in some cholinergic motor neurons in the
medulla of SIDS infants. This could lead to abnormal control of cardiovascular
and respiratory function and airway patency and may be one of the contributing
factors in the etiology of SIDS.
PMID- 10197818
TI - Apoptosis of neurons in the dentate gyrus in humans suffering from bacterial
meningitis.
AB - Apoptosis of granular cells in the dentate gyrus frequently occurs in animal
models of bacterial meningitis. In 37 autopsy cases of bacterial meningitis we
evaluated, by light microscopy and in-situ tailing, whether this pattern of
neuronal damage is of relevance in humans. Neuronal apoptoses in the dentate
gyrus (density 1 to 19/mm2) were observed in 26 cases of bacterial meningitis and
in none of 10 aged-matched control cases dying from non-neurological diseases.
The density of apoptotic neurons depended on the interval between the onset of
symptoms of meningitis and death (death within the first 2 days: 1.8+/-2.8
apoptoses/mm2; later than 18 days: 1.8+/-1.7/mm2; compared to death between days
3 and 18: 7.4+/-6.6 apoptoses/mm2, p = 0.007 and 0.004, respectively). Neuronal
apoptosis in the dentate gyrus was not linked to neuronal damage in other parts
of the brain or previous treatment with corticosteroids. Since learning deficits
are frequently observed in survivors of bacterial meningitis, strategies to
reduce the density of apoptotic neurons in the dentate gyrus may decrease the
frequency of neurological sequela in patients surviving bacterial meningitis.
PMID- 10197819
TI - Quantitative decrease in synaptophysin message expression and increase in
cathepsin D message expression in Alzheimer disease neurons containing
neurofibrillary tangles.
AB - Combining immunocytochemistry with in situ hybridization of Alzheimer disease
(AD) hippocampus demonstrated a 50% reduction in grain density for synaptophysin
message over CA1 pyramidal neurons containing neurofibrillary tangles (NFT)
relative to near neighbor NFT-free neurons. This decrease was not global, but was
selective since message grain density for the lysosomal protein, cathepsin D,
increased 33% in these neurons (relative to NFT-free neurons). Poly A+ message
grain density decreased by 25% in NFT neurons. Percent of the cell body
containing NFT correlated -0.35 (p < 0.0001) with grain density for synaptophysin
message. These data verify the concept of altered profiles of gene expression as
a function of disease state within single cells and suggest that events
associated with NFT formation may lead to altered expression of synaptic
messages.
PMID- 10197820
TI - Apolipoprotein E alters metabolism of AbetaPP in cells engaged in beta
amyloidosis.
AB - Canine smooth muscle cells (SMCs), cultured from amyloid-affected brain blood
vessels accumulate Alzheimer amyloid-beta peptide (Abeta) intracellularly, either
spontaneously or after treatment with apolipoprotein E (apoE). ApoE is
codeposited with Abeta, which suggests that apoE participates in Abeta
accumulation. We tested the hypothesis that apoE-induced accumulation of Abeta in
SMCs is caused by an increased production of amyloid-beta precursor protein
(AbetaPP) and/or its altered metabolism. We found that 24 hours of treatment with
apoE3 or apoE4 induced intracellular accumulation of Abeta-immunoreactive
deposits in SMCs but did not influence AbetaPP production and processing. The
treatment with apoE3 or E4 for 3 days resulted in the following: increased Abeta
accumulation; reduced levels of secreted Abeta; increased production and cellular
retention of mature AbetaPP770; and reduced culture growth, cell proliferation,
and viability. ApoE4, but not apoE3, increased cellular levels of mRNA AbetaPP
770 (the main form produced in SMCs) about ninefold. ApoE3 stimulated production
and cellular retention of endogenous apoE. We hypothesize that Abeta accumulation
is triggered by apoE, which may bind and immobilize soluble Abeta produced in
SMCs. The newly formed Abeta deposits may further accelerate Abeta accumulation
by altering metabolism of AbetaPP.
PMID- 10197823
TI - Do the intracellular calcium states in Alzheimer disease need to be revisited?
PMID- 10197821
TI - Evidence for neuroprotective effects of acidic fibroblast growth factor in
Alzheimer disease.
AB - Recent studies indicate that fibroblast growth factors (FGFs) might confer
neuroprotection against excitotoxicity. Therefore, the fact that acidic FGF
(aFGF) is more abundant in motoneurons than in the hippocampal formation suggests
that aFGF contributes to the selective vulnerability of neurons in entorhinal
cortex (EC) in Alzheimer disease (AD). In order to understand the role of aFGF in
AD, patterns of aFGF FGF receptor (FGFR), and N-methyl-D-aspartate (NMDA)
receptor (NMDAR) expression in the EC and hippocampus of AD and control cases
were investigated, and effects of aFGF on excitotoxicity were examined in vitro.
In AD, the number of aFGF immunolabeled neurons was decreased in EC, while the
remaining neurons showed significantly higher aFGF immunoreactivity. This latter
group of neurons did not show cytoskeletal abnormalities. Acidic FGF and FGFR
immunoreactivity were positively correlated, whereas a negative correlation was
found between aFGF and NMDAR expression. These results were confirmed in vitro
utilizing NT2N cells. Higher levels of FGFR protein were expressed in aFGF
treated cells, while less NMDAR protein was found compared with untreated cells.
Furthermore, exposure of treated and untreated NT2N cell to glutamate revealed
that aFGF can prevent glutamate induced cell death. Taken together these data
suggest that aFGF regulates the expression of NMDAR and FGFR and thereby
contributes to neuroprotection against glutamate excitotoxicity. Therefore,
altered patterns of aFGF immunoreactivity in EC in AD are an important marker for
selective vulnerability of EC neurons.
PMID- 10197824
TI - Transcranial magnetic stimulation: applications in neuropsychiatry.
AB - In the 1990s, it is difficult to open a newspaper or watch television and not
find someone claiming that magnets promote healing. Rarely do these claims stem
from double-blind, peer-reviewed studies, making it difficult to separate the
wheat from the chaff. The current fads resemble those at the end of the last
century, when many were falsely touting the benefits of direct electrical and
weak magnetic stimulation. Yet in the midst of this popular interest in magnetic
therapy, a new neuroscience field has developed that uses powerful magnetic
fields to alter brain activity--transcranial magnetic stimulation. This review
examines the basic principles underlying transcranial magnetic stimulation, and
describes how it differs from electrical stimulation or other uses of magnets.
Initial studies in this field are critically summarized, particularly as they
pertain to the pathophysiology and treatment of neuropsychiatric disorders.
Transcranial magnetic stimulation is a promising new research and, perhaps,
therapeutic tool, but more work remains before it can be fully integrated in
psychiatry's diagnostic and therapeutic armamentarium.
PMID- 10197825
TI - Therapeutic efficacy of right prefrontal slow repetitive transcranial magnetic
stimulation in major depression: a double-blind controlled study.
AB - BACKGROUND: Transcranial magnetic stimulation (TMS), a noninvasive technique for
stimulation of the brain, has recently been suggested to be effective for the
treatment of major depression. We conducted a double-blind, placebo-controlled
study to assess the efficacy of slow repetitive TMS (rTMS) in patients with major
depression. METHODS: Seventy patients with major depression (53 women, 17 men;
mean age, 58.7 years; SD, 17.2 years) were randomly assigned to receive rTMS or
sham rTMS in a double-blind design. Treatment was administered in 10 daily
sessions during a 2-week period. Severity of depression was blindly assessed
before, during, and after completion of the treatment protocol. RESULTS: All
patients completed the first week of treatment and 67 completed the entire
protocol. Patients who received rTMS had a significantly greater improvement in
depression scores compared with those who received sham treatment. At the end of
2 weeks, 17 of 35 patients in the rTMS group, but only 8 of 32 in the sham
treated group, had an improvement of greater than 50% in their depression
ratings. CONCLUSIONS: This controlled study provides evidence for the short-term
efficacy of slow rTMS in patients with recurrent major depression. Additional
studies will be necessary to assess the efficacy of rTMS as compared with
electroconvulsive therapy as well as the long-term outcome of this treatment in
major depression and possibly other psychiatric disorders.
PMID- 10197826
TI - Clinical characteristics of major depression that predict risk of depression in
relatives.
AB - BACKGROUND: Major depression (MD) is both clinically and etiologically
heterogeneous. We attempt to relate clinical and etiologic heterogeneity by
determining those features of MD that reflect a high familial liability to
depressive illness. METHODS: Our sample, 3786 personally interviewed twin pairs
from a population-based registry, contained 1765 people with a lifetime history
of MD by DSM-III-R criteria, of whom 639 (36.2%) had affected co-twins. We
examine, using Cox proportional hazard models, the clinical features of MD in
affected twins that predicted the risk for MD in the co-twin. Control variables
were zygosity, age at interview, and sex of the twin and co-twin. RESULTS: The
best-fitting model contained 4 significant predictors: number of episodes,
duration of longest episode, recurrent thoughts of death or suicide, and level of
distress or impairment. These 4 clinical features were similarly predictive of
the risk for MD in the co-twins of male and female twins and predicted risk of
illness more strongly in monozygotic than in dizygotic twins. Variables that did
not uniquely predict risk of MD in the co-twin included age at onset and number
of depressive symptoms. For number of episodes, the best-fitting model indicated
an inverted U-shaped function with greatest co-twin risk for MD with 7 to 9
lifetime episodes. CONCLUSIONS: The clinical features of MD in epidemiologic
samples can be meaningfully related to the familial vulnerability to illness.
Familial MD is best characterized by intermediate levels of recurrence, long
duration of episodes, high levels of impairment, and recurrent thoughts of death
or suicide. These clinical features probably reflect a high genetic liability to
depressive illness.
PMID- 10197827
TI - Long-term methylphenidate therapy in children with comorbid attention-deficit
hyperactivity disorder and chronic multiple tic disorder.
AB - BACKGROUND: This study examined changes in attention-deficit hyperactivity (ADHD)
behaviors and motor and vocal tics during long-term treatment with
methylphenidate. METHODS: Thirty-four prepubertal children with ADHD and chronic
multiple tic disorder (who had participated in an 8-week, double-blind, placebo
controlled methylphenidate evaluation) were evaluated at 6-month intervals for 2
years as part of a prospective, nonblind, follow-up study. Treatment effects were
assessed using direct observations of child behavior in a simulated (clinic
based) classroom and behavior rating scales completed by parents and physician.
Videotapes of the simulated classroom were scored by coders who were blind to
treatment status. RESULTS: There was no evidence (group data) that motor tics or
vocal tics changed in frequency or severity during maintenance therapy compared
with diagnostic or initial double-blind placebo evaluations. Behavioral
improvements demonstrated during the acute drug trial were maintained during
follow-up. There was no evidence (group data) of clinically significant adverse
drug effects on cardiovascular function or growth at the end of 2 years of
treatment. CONCLUSIONS: Long-term treatment with methylphenidate seems to be safe
and effective for the management of ADHD behaviors in many (but not necessarily
all) children with mild to moderate tic disorder. Nevertheless, careful clinical
monitoring is mandatory to rule out the possibility of drug-induced tic
exacerbation in individual patients.
PMID- 10197828
TI - Stimulants and tic disorders: from dogma to data.
PMID- 10197829
TI - Education and peer discussion group interventions and adjustment to breast
cancer.
AB - BACKGROUND: We report a clinical trial comparing the effectiveness of education
based and peer discussion-based group interventions on adjustment to breast
cancer. METHODS: Women with stage I, II, or III breast cancer (n = 312) were
randomly assigned to 1 of 4 group conditions: control, education, peer
discussion, or education plus peer discussion (combination). Seven groups (each
comprising 8-12 women) were conducted in each of the 4 conditions (28 groups
total). Adjustment was measured before the intervention, immediately after the
intervention, and 6 months after the intervention. RESULTS: Consistently positive
effects on adjustment were seen in the education groups both immediately
following and 6 months after the intervention. There were no benefits of
participation in peer discussion groups, and some indications of adverse effects
on adjustment at both follow-up examinations. The effects could be explained by
changes in self-esteem, body image, and intrusive thoughts about the illness.
CONCLUSIONS: Education-based group interventions facilitated the initial
adjustment of women diagnosed with early stage breast cancer. There was no
evidence of benefits from peer discussion group interventions.
PMID- 10197830
TI - Report of the Institute of Medicine Committee on the Efficacy and Safety of
Halcion.
PMID- 10197831
TI - The report by the Institute of Medicine and postmarketing surveillance.
PMID- 10197832
TI - Long-term use of sedative and hypnotic medication.
PMID- 10197833
TI - Hippocampal volume in patients with alcohol dependence.
AB - BACKGROUND: Smaller hippocampal volumes have been reported in the brains of
alcoholic patients than in those of healthy subjects, although it is unclear if
the hippocampus is disproportionally smaller than the brain as a whole. There is
evidence that alcoholic women are more susceptible than alcoholic men to liver
and cardiac damage from alcohol. It is not known whether the hippocampi of the
female brain are more vulnerable to alcohol. METHODS: We compared the hippocampal
volumes in 52 hospitalized alcoholic men and women with those of 36 healthy
nonalcoholic men and women. All subjects were between 27 and 53 years of age. The
hippocampal volumes were measured from sagittal T-weighted high-resolution
magnetic resonance images. RESULTS: The alcoholic women had less lifetime
drinking and a later age at onset of heavy drinking than alcoholic men. Both
alcoholic men and women had significantly smaller right hippocampi and larger
cerebrospinal fluid volumes than healthy subjects of the same sex. Only among
women were the left hippocampus and the nonhippocampal brain volume also
significantly smaller. The proportion of hippocampal volume relative to the rest
of the brain volume was the same in alcoholic patients and healthy subjects, in
both men and women. The right hippocampus was larger than the left among all
subjects. Women demonstrated larger hippocampal volumes relative to total brain
volume than men. Psychiatric comorbidity, including posttraumatic stress
disorder, did not affect hippocampal volume. CONCLUSIONS: In chronic alcoholism,
the reduction of hippocampal volume is proportional to the reduction of the brain
volume. Alcohol consumption should be accounted for in studies of hippocampal
damage.
PMID- 10197834
TI - Compromised white matter tract integrity in schizophrenia inferred from diffusion
tensor imaging.
AB - BACKGROUND: Current investigations suggest that brain white matter may be
qualitatively altered in schizophrenia even in the face of normal white matter
volume. Diffusion tensor imaging provides a new approach for quantifying the
directional coherence and possibly connectivity of white matter fibers in vivo.
METHODS: Ten men who were veterans of the US Armed Forces and met the DSM-IV
criteria for schizophrenia and 10 healthy, age-matched control men were scanned
using magnetic resonance diffusion tensor imaging and magnetic resonance
structural imaging. RESULTS: Relative to controls, the patients with
schizophrenia exhibited lower anisotropy in white matter, despite absence of a
white matter volume deficit. In contrast to the white matter pattern, gray matter
anisotropy did not distinguish the groups, even though the patients with
schizophrenia had a significant gray matter volume deficit. The abnormal white
matter anisotropy in patients with schizophrenia was present in both hemispheres
and was widespread, extending from the frontal to occipital brain regions.
CONCLUSIONS: Despite the small sample size, diffusion tensor imaging was powerful
enough to yield significant group differences, indicating widespread alteration
in brain white matter integrity but not necessarily white matter volume in
schizophrenia.
PMID- 10197836
TI - Omega-3 fatty acids--the missing link?
PMID- 10197835
TI - A double-blind, randomized, placebo-controlled trial of pindolol augmentation in
depressive patients resistant to serotonin reuptake inhibitors. Grup de Recerca
en Trastorns Afectius.
AB - BACKGROUND: Pindolol has been reported to hasten the antidepressant action of
selective serotonin reuptake inhibitors in open-label and placebo-controlled
trials. Pilot studies also suggested that pindolol could augment the
antidepressant response in unresponsive patients. We investigated whether the
addition of pindolol can induce a rapid response in treatment-resistant patients.
METHODS: After a single-blind lead-in placebo phase of 5 days to exclude placebo
responders, 80 outpatients with major depression who did not respond to a minimum
of 6 weeks of treatment with clomipramine hydrochloride, 150 mg/d; fluoxetine
hydrochloride, 40 mg/d; fluvoxamine maleate, 200 mg/d; or paroxetine
hydrochloride, 40 mg/d, were randomly assigned to additionally receive placebo (3
times daily) or pindolol (2.5 mg 3 times daily) for 10 days. The median number of
ineffective treatments in the current episode was 2 (range, 1-4). Hamilton Rating
Scale for Depression and Montgomery-Asberg Scale for Depression scores were used
as primary measures of efficacy. RESULTS: At end point, the Hamilton and
Montgomery-Asberg scores and change from baseline in Hamilton score were not
significantly different in patients taking placebo or pindolol. The response rate
was equal in both groups (12.5%). No differences in the clinical outcome were
found when the various pretreatment subgroups were considered. At end point, the
plasma concentration of pindolol was 9.9+/-5.1 ng/mL (mean +/- SD; n = 40).
CONCLUSIONS: Although pindolol can accelerate the antidepressant action of
selective serotonin reuptake inhibitors in previously untreated patients, it does
not elicit a rapid clinical response in treatment-resistant patients within a 10
day period.
PMID- 10197837
TI - Laparoscopic live donor nephrectomy: pro.
PMID- 10197838
TI - Laparoscopic live donor nephrectomy: con.
PMID- 10197839
TI - Phytotherapy in the treatment of benign prostatic hyperplasia: an update.
PMID- 10197840
TI - Pheochromocytomas: can malignant potential be predicted?
AB - OBJECTIVES: The presence of metastatic lesions is the only acceptable fact to
confirm malignant pheochromocytoma. Patients with malignant pheochromocytomas,
however, have a very poor survival rate. The aim of our study was to postulate
predictive values for malignant pheochromocytomas. METHODS: We evaluated
symptoms, diagnostic modalities, treatment, and long-term follow-up of 86
patients with 85 benign and 10 malignant pheochromocytomas. Parameters from the
benign were compared with those of the malignant pheochromocytomas. RESULTS:
Preoperative 24-hour urinary dopamine was in the normal range for benign
pheochromocytomas but increased in malignant pheochromocytomas (P<0.0001).
Vanillylmandelic acid was elevated in both benign and malignant pheochromocytomas
but higher in malignant than in benign tumors (P = 0.01). No differences could be
shown in urinary epinephrine and norepinephrine samplings. Tumor location was
divided into 77 adrenal (81%) and 18 extra-adrenal (19%) sites. Malignant
pheochromocytomas were located more often at extra-adrenal sites (P = 0.03).
There was no increased incidence of malignancy in patients with familial
bilateral pheochromocytomas or multiple endocrine neoplasia. Tumors greater than
80 g in weight corresponded to malignancy (P<0.0001). Dopamine tumor
concentration was higher in malignant than in benign pheochromocytomas (P =
0.01). Persistent arterial hypertension occurred in 9 (13%) of 72 benign and 6
(60%) of 10 malignant pheochromocytomas (P = 0.001). The 10-year survival rate
was 94% for benign pheochromocytomas. All patients with malignant
pheochromocytomas died within this period (P = 0.0001). CONCLUSIONS: High
preoperative 24-hour urinary dopamine levels, extra-adrenal tumor location, high
tumor weight, elevated tumor dopamine concentration, and postoperative persistent
arterial hypertension are all factors that increase the likelihood of malignant
pheochromocytoma. Patients with these characteristics should have more frequent
follow-up evaluations to identify malignancy at earlier states.
PMID- 10197841
TI - Tubular dysplasia and carcinoma in situ: precursors of renal cell carcinoma.
AB - OBJECTIVES: To identify the dysplastic changes in tubules adjacent to or remote
from renal cell carcinoma (RCC) and to assess proliferating cell nuclear antigen
(PCNA) expression of normal tubule and carcinoma cells. METHODS: The study
analyzed 62 kidneys with RCC that were removed by radical nephrectomy. Pathologic
sections were stained with hematoxylin-eosin and evaluated for the presence of
dysplasia. Sections that contained dysplasia were then stained by the avidin
biotin immunoperoxidase technique after epitope retrieval for PCNA. RESULTS:
Dysplastic changes in normal kidney were identified in 14 cases (23%). Dysplastic
changes were adjacent to the tumor in 10 cases. Dysplasia was adjacent to the
tumor and diffuse in 6 cases (3 clear cell [CRCC], 2 chromophobe [ChRCC], 1
sarcomatoid RCC [SRCC]), adjacent to the tumor and focal in 4 cases (2 CRCC, 1
papillary RCC, 1 SRCC), remote and focal in 3 cases (1 granular RCC, 1 ChRCC, 1
SRCC), and remote and diffuse in 1 case (CRCC). The lesions represented a focus
that could be defined as carcinoma in situ in 3 cases. PCNA immunostaining in
dysplastic epithelia was more intense than that in normal tubules and was as
intense or even more intense than that in carcinoma cells. CONCLUSIONS: Dysplasia
of tubular epithelium is probably a biologic precursor of at least some RCC.
Tubular dysplasia warrants further study as an important phase that will provide
new insights into the pathogenesis, biologic behavior, and natural history of
RCC. Its impact on the surgical management of small unilateral RCC needs to be
investigated.
PMID- 10197842
TI - Efficacy of finasteride is maintained in patients with benign prostatic
hyperplasia treated for 5 years. The North American Finasteride Study Group.
AB - OBJECTIVES: The purpose of this open-label study extension was to assess the long
term safety and efficacy of finasteride in the treatment of men with benign
prostatic hyperplasia (BPH). METHODS: A Phase III North American BPH trial
originally enrolled 895 men, 297 of whom were randomized to receive finasteride 5
mg. An enlarged prostate gland by digital rectal examination, symptoms of urinary
obstruction, and a maximal urinary flow rate of less than 15 mL/s were required
for entry. Patients who completed the initial 12-month, double-blind, placebo
controlled study were invited to participate in an open-label extension for 4
additional years. RESULTS: Of the 297 patients initially randomized to receive
finasteride 5 mg, 259 completed 12 months in the double-blind period and 186
completed 48 months of open-label therapy. Prostate volume reached a nadir of
24.6% at month 24, and the effect was maintained through month 60. Compared with
baseline values, month 60 prostate volume was decreased by 22.7% (P<0.001), the
quasi-American Urological Association symptom score was decreased by 4.3 points,
and maximal urinary flow was increased by 2.3 mL/s (P<0.001) on average.
Finasteride was well tolerated, with no significant increase in the prevalence of
sexual adverse events over time. CONCLUSIONS: Patients treated with finasteride 5
mg maintained an initial decrease in prostate volume and improvement in symptom
score and maximal urinary flow rate over 5 years.
PMID- 10197843
TI - Does long-term finasteride therapy affect the histologic features of benign
prostatic tissue and prostate cancer on needle biopsy? PLESS Study Group. Proscar
Long-Term Efficacy and Safety Study.
AB - OBJECTIVES: Finasteride, a common agent used to treat benign prostatic
hyperplasia (BPH), inhibits 5-alpha-reductase. Testosterone is converted by 5
alpha-reductase to the more potent dihydrotestosterone, which is the primary
androgen in the prostate. Leuprolide is a stronger antiandrogen that is used to
downstage prostate cancer before radical prostatectomy. Leuprolide induces marked
atrophy of prostate carcinoma cells, which sometimes makes pathologic diagnosis
of cancer difficult, although evaluation at radical prostatectomy is easier than
at biopsy. It is unknown whether finasteride produces similar changes, which
would result in greater diagnostic difficulty because such changes would be seen
on biopsy to rule out cancer in men with suspicious clinical findings treated for
BPH. The current study investigated the histologic effects of finasteride therapy
on human prostate cancer and benign prostatic tissue on needle biopsy. METHODS:
In blinded manner, we reviewed 53 needle biopsy specimens showing prostate
carcinoma (35 treated with finasteride, 18 with placebo). Also reviewed in
blinded manner were 50 benign needle biopsy specimens (25 treated with
finasteride, 25 with placebo). The Gleason score, number of cores involved,
percentage cancer involvement in a core, percentage of atrophic changes in cancer
cells, presence of mitoses, blue-tinged mucinous secretions, prominent nucleoli,
and high-grade prostatic intraepithelial neoplasia were documented for each case
in the cancer group. The percentage of atrophy, basal cell hyperplasia,
transitional metaplasia, chronic inflammation, and stromal proliferation was
documented for each case in the benign group. RESULTS: No significant histologic
differences were present in either the benign or cancer group between cases
treated with finasteride and placebo. CONCLUSIONS: We conclude that finasteride
treatment for BPH does not cause difficulty in the diagnosis of cancer in
prostate needle specimens. It is possible that there are severely atrophic areas
resulting from finasteride treatment that are undersampled. However, the
conclusion that cancer seen on needle biopsy in men treated with finasteride is
unaltered and readily identified as cancer remains valid.
PMID- 10197844
TI - Heritability of the symptoms of benign prostatic hyperplasia and the roles of age
and zonal prostate volumes in twins.
AB - OBJECTIVES: Both benign prostatic hyperplasia and lower urinary tract symptoms
(LUTS) have been shown to increase with age in men, but a causal relationship
between prostate volume and symptoms has not been established. This study had two
aims, to investigate the inter-relationships of age, symptoms, and various zonal
measurements in the prostate and to assess the impact of heritable influences on
symptom score. METHODS: Eighty-three monozygotic twin pairs and 83 dizygotic twin
pairs were studied to determine age and LUTS as assessed by the American
Urological Association symptom score. Their prostate volumes (total, transition
zone, and peripheral zone) were measured by transrectal ultrasound. RESULTS:
There was significant evidence of pairwise correlation between transition zone
and symptom score (P = 0.04) and between age and symptom score (P = 0.03). Age
also showed significant correlation with all volume measurements. Heritability
appears to account for 82.6% of the variability in symptom score in men older
than 50 years. CONCLUSIONS: This study provides evidence that age and transition
zone volume play a role in LUTS, but also that their influence is not strong.
Estimates of heritability suggest that hereditary factors contribute
substantially to LUTS.
PMID- 10197845
TI - E-cadherin expression as a marker of tumor aggressiveness in routinely processed
radical prostatectomy specimens.
AB - OBJECTIVES: Approximately 30% of clinically localized prostate adenocarcinomas
treated by radical prostatectomy (RP) will recur within 10 years. To prevent
recurrence, new adjuvant therapies are in development that seek to treat high
risk patients after surgery. To identify patients as candidates for these
treatments, improved biomarkers for predicting prognosis are needed. Reduced
expression of E-cadherin has been proposed as a new marker for predicting
prognosis in prostate adenocarcinoma. Since few studies have examined the
relation between risk factors for disease progression and E-cadherin expression
using routinely processed RP specimens, we used RP specimens to correlate
downregulation of E-cadherin and pathologic stage at RP. METHODS: Primary
adenocarcinomas (n = 76) from formalin-fixed and paraffin-embedded RP specimens
were evaluated by immunohistochemistry against E-cadherin (HECD-1) using heat
induced epitope retrieval and automated staining (BioTek Solutions). Normal
appearing prostate epithelium was used as an internal control for each specimen.
Staining was scored as an estimate of the percentage of tumor cells in each
specimen that showed strong plasma membrane staining. RESULTS: Specimens were
divided into three categories with respect to Gleason score: intermediate (score
5 to 6, n = 31), intermediate to high (score 7, n = 25), and high (score 8 to 9,
n = 20). For pathologic stage, specimens were divided into three categories: low
stage/organ confined (pT2, n = 30), intermediate stage/limited extraprostatic
extension (pT3a, n = 25), and high stage/seminal vesicle-pelvic lymph node
metastases (pT3b-any pTN1, n = 21). In univariate analysis, reduced levels of E
cadherin correlated with advanced Gleason score (P = 0.003) and advanced
pathologic stage (P = 0.008). In multivariate analysis, E-cadherin, preoperative
prostate-specific antigen, and Gleason score all contributed independently to the
prediction of high-stage disease (P<0.0001). Ten pelvic lymph node metastases
from this same patient cohort were stained for E-cadherin. All were positive and
9 of 10 were moderately to strongly positive. CONCLUSIONS: Since essentially all
patients in the high-stage category have a very high likelihood of disease
recurrence, we conclude that the study of E-cadherin in a prospective manner as a
potential biomarker of disease progression in patients with clinically organ
confined prostate cancer who undergo RP is warranted. Additionally, our finding
that most metastatic tumor cells in pelvic lymph nodes express E-cadherin
supports the notion that the establishment of the distant colonization and growth
of metastatic tumor cells may be facilitated by expression or re-expression of
previously downregulated E-cadherin. This would strongly suggest that
irreversible genetic inactivation through mutation or allelic loss at 16q2.3 is
probably not the mechanism of E-cadherin downregulation in most abnormally
expressing primary prostate carcinomas.
PMID- 10197846
TI - Blinded evaluation of reverse transcriptase-polymerase chain reaction prostate
specific antigen peripheral blood assay for molecular staging of prostate cancer.
AB - OBJECTIVES: The reverse transcriptase-polymerase chain reaction (RT-PCR)-prostate
specific antigen (PSA) assay to detect presumed occult micrometastatic prostate
cancer has been controversial, and this molecular staging has been thought to be
clinically useful by some groups but not others. METHODS: We used a sensitive
nested RT-PCR assay with specific primers derived from the PSA sequence and a
very stringent two-step PCR protocol with denaturing temperature of 94 degrees C
annealing and extension temperature of 68 degrees C. This method enabled us to
detect PSA-expressing LNCaP prostate cancer (PC) cells as low as one cell of 10
million lymphocytes (1/10(7)). Ninety-six patients with PC were studied,
including 85 before radical prostatectomy (RP), and 22 controls, including
healthy men and women and men with benign prostatic hyperplasia. RESULTS: In 85
patients undergoing RP, a minimum of two independent RT-PCR-PSA assays detected
circulating prostate cells preoperatively in 27 patients (31.8%). Of 12 patients
with locally advanced or advanced stage cancer, RT-PCR-PSA was positive in 5
(41.7%); of the 22 controls, no patient was RT-PCR-PSA positive. In 10 randomly
selected cases, the RT-PCR product was confirmed as PSA by DNA sequencing. Of the
27 patients undergoing RP who were RT-PCR positive, 11 (40.7%) had non-organ
confined disease (pT3a or greater), and of the 58 patients who were RT-PCR
negative, 32 (55.2%) had non-organ-confined disease. Patients with RT-PCR
positive results also had lower margin positivity (9 of 27, 33.3%) than did
patients with RT-PCR negative results (21 of 58, 36.2%). Finally, at a mean
follow-up of 25.7 months, 5 (18.5%) of 27 RT-PCR positive patients had recurrence
(PSA) compared with 14 (24.1%) of 58 RT-PCR negative patients. CONCLUSIONS: On
the basis of this blinded study, RT-PCR for PSA-expressing cells in 85 patients
before RP is not related to clinical stage, age, race, grade, Gleason sum, serum
PSA or prostatic acid phosphatase, tumor volume, or tumor multifocality. RT-PCR
positivity did not predict pathologic stage or early PSA recurrence. A
standardized RT-PCR assay needs to be developed to account for interlaboratory
discrepancies.
PMID- 10197847
TI - Serum half-life time determination of free and total prostate-specific antigen
following radical prostatectomy--a critical assessment.
AB - OBJECTIVES: All studies investigating the elimination kinetics of serum total
(tPSA) and free (fPSA) prostate-specific antigen (PSA) were carried out in men
undergoing radical prostatectomy. Radical prostatectomy itself could, however,
have a major influence on the serum concentration of these tumor markers (e.g.,
perioperative fluid shift or blood loss). The purpose of our study was to
determine the half-life time of fPSA and tPSA with special regard to the
influence of the radical prostatectomy on the serum concentration of these tumor
markers. METHODS: Eleven men (mean age 63.2+/-7.2 years) with organ-confined
prostate cancer who underwent radical prostatectomy were investigated (final
pathologic Stage pT2pN0 or lower). Serum samples were obtained preoperatively and
0.25, 0.5, 1, 2, 4, 8, 12, 16, 24, 48, 72, 120, 168, and 240 hours after removal
of the prostate. fPSA and tPSA and albumin and total protein serum concentrations
were determined in all samples. RESULTS: During the first 120 minutes after
removal of the prostate, albumin and total protein serum concentrations
continuously declined, with a half-life time of -104.5+/-28 minutes and -129.7+/
32 minutes, respectively. Serum decline of fPSA and tPSA followed a biphasic
kinetic. During the initial alpha-phase, fPSA and tPSA serum concentrations
decreased, with a half-life time of -69+/-10.3 minutes and -87.3+/-18.1 minutes,
respectively. During the terminal beta-phase, the half-life time of fPSA and tPSA
was -1152.2 minutes (0.8 days) and -3916.1 minutes (2.7 days), respectively.
Between the alpha-phase half-life time of fPSA or tPSA and the half-life time of
the total protein or albumin concentration decline, significant correlations were
found. CONCLUSIONS: These correlations indicate that the rapid decline of fPSA
and tPSA directly after removal of the prostate (alpha-phase half-life time) is
caused by the radical prostatectomy itself. The half-life time of the beta-phase
reflects the biologic clearance of PSA. Therefore, the half-life time
determination of PSA after radical prostatectomy is of limited value if the
influence of the operation itself on the serum PSA concentration is not taken
into account.
PMID- 10197848
TI - Kinetics of postbiopsy levels of serum free prostate-specific antigen and percent
free prostate-specific antigen.
AB - OBJECTIVES: We evaluated the effects of transrectal ultrasound-guided biopsy of
the prostate on serum total and free prostate-specific antigen (PSA) and the
free/total PSA ratio and factors affecting variations in PSA levels. METHODS:
Serum total and free PSA levels and the free/total PSA ratio were determined in
48 men (mean age 66+/-7 years) before and 1 hour, 8 days, and 30 days after
prostate biopsy. At least six cores were taken using a biopsy gun with an 18
gauge needle. The coefficient of variation of PSA was calculated as the
postbiopsy/prebiopsy PSA ratio. Changes in PSA levels and the coefficient of
variation were studied. RESULTS: Fifteen (31%) of 48 men had adenocarcinoma on
biopsy. Total and free PSA values were significantly increased 1 hour and 8 days
after biopsy, and both returned to baseline 30 days after biopsy. The free/total
PSA ratio was significantly increased (55%) 1 hour after biopsy and significantly
decreased (12%) 8 days after biopsy. Thirty days after biopsy, the median of the
free/total PSA ratio (18%) was not significantly different from the prebiopsy
ratio (16%). The median of the coefficient of variation of the free/total PSA
ratio was 3, 0.7, and 1 at 1 hour, 8 days, and 30 days after biopsy,
respectively. Age, prostate volume, number of cores, and digital rectal
examination and histologic findings were not significantly associated with
variation in percent free PSA. Variation in percent free PSA at day 8 was
associated with prebiopsy total PSA value and the free/total PSA ratio.
CONCLUSIONS: Prostate biopsy dramatically alters the percent free PSA. The
free/total PSA ratio was decreased 8 days after biopsy and returned to prebiopsy
levels in 75% of patients at 1 month after biopsy. Measurement of free PSA levels
and the free/total PSA ratio should not be done within 4 weeks of prostate
biopsy.
PMID- 10197849
TI - Free/total PSA ratio improves differentiation of benign and malignant disease of
the prostate: critical analysis of two different test populations.
AB - OBJECTIVES: To evaluate the ability of free PSA (fPSA), total PSA (tPSA), and the
free/total PSA (f/t PSA) ratio to differentiate between benign prostate disease
(benign prostatic hyperplasia [BPH] and no evidence of malignancy [NEM]) and
prostate cancer (CaP) using two different testing populations, and to compare
predictive probabilities for the two test populations. METHODS: One test
population consisted of sera from 531 men with clinically well-defined and biopsy
confirmed BPH (n = 255) or CaP (n = 276), with tPSA values ranging from 2 to 20
ng/mL. All of these serum samples were retrospective and obtained from patients
evaluated in academic settings before any treatment. A second test population
consisted of a prospective analysis of sera obtained from 4870 men, collected by
urologists throughout the United States and processed at a single pathology
laboratory. All these patients had a systematic biopsy evaluated and diagnosed at
the same pathology laboratory, with the diagnosis categorized as either NEM (n =
2961) or CaP (n = 1909). No additional information on concurrent disease or pre-
or current treatment status was known for this test population. For both
populations, two tPSA reflex range groups, 2 to 10 and 2 to 20 ng/mL, were
evaluated. RESULTS: Both test populations benefited from the application of
either fPSA alone or the f/t PSA ratio to differentiate benign from malignant
disease (t test P value less than 0.001). The receiver operating characteristic
(ROC) curve for the f/t PSA ratio had an area under the curve (AUC) of 72% for n
= 531 versus 63% for n = 4870, irrespective of the tPSA reflex range. Average
fPSA values demonstrated a linear correlation to a range of tPSA concentrations
for both test populations. Predictive probabilities (adjusted for established
cancer prevalence rates in the academic population [n = 531]) calculated using
f/t PSA ratios also demonstrated their value in contrasting the performance
characteristics in the two test populations. CONCLUSIONS: The fPSA and f/t PSA
ratio improved the differentiation of benign disease and CaP in two different
patient samples. The f/t PSA ratio demonstrated an increased sensitivity and
specificity when applied to differentiate clinically well-defined BPH and CaP (n
= 531). The differences in the results between the two test samples are probably
attributable to the variability of the patient's disease and treatment status in
the larger, less refined, community-based population. The use of predictive
probabilities provides the opportunity to provide patient-specific cancer
probabilities instead of using population-based specific single cutoffs.
PMID- 10197850
TI - Polyclonal and monoclonal antibodies to prostate-specific antigen can cross-react
with human kallikrein 2 and human kallikrein 1.
AB - OBJECTIVES: The human tissue kallikrein family contains three closely related
proteases: human kallikrein 1 (hK1), human kallikrein 2 (hK2), and prostate
specific antigen (PSA). The structural homology between these three proteins
suggests potential cross-reactivity interference when different immunologic
techniques are used. This study evaluated PSA and hK2 monoclonal antibody (mAb)
and polyclonal antibody (pAb) reactivities to hK1, hK2, and PSA. METHODS: mAbs
and pAbs to hK2 and PSA were evaluated using Western blot analysis on hK1, hK2,
PSA, and seminal plasma. RESULTS: pAbs to PSA and hK2 recognized all three human
kallikreins, as well as fragments of hK2 and PSA. An mAb with minimal (less than
0.4%) cross-reactivity between PSA and hK2 and a cross-reactive mAb were found.
mAbs specific to PSA or hK2 did not cross-react with the less homologous hK1
protein. A PSA mAb raised specifically to PSA fragments recognized both PSA and
hK2 but did not cross-react with hK1. pAbs to hK1 cross-reacted slightly with PSA
and not at all with hK2. CONCLUSIONS: Both pAbs and mAbs to hK2 and PSA may
exhibit immunocross-reactivity. pAbs to PSA or hK2 react with all three human
tissue kallikreins. The potential for cross-reactivity should be considered in
any clinical or research procedures that use hK1, hK2, and PSA antibodies.
PMID- 10197851
TI - Excision of the neurovascular bundle at radical prostatectomy in cases with
perineural invasion on needle biopsy.
AB - OBJECTIVES: To assess, in a group of patients who had undergone radical
prostatectomy and who were likely to have extraprostatic extension of their
tumors based on the previous finding of perineural invasion on needle biopsy, how
effective excision of the neurovascular bundle was in reducing the number of
positive margins and increasing the potential cure rate. METHODS: Eighty radical
prostatectomy cases from our institution that had perineural invasion on prostate
needle biopsy were retrospectively studied to determine the presence and location
of extraprostatic extension, positive margins, and seminal vesicle or lymph node
involvement, whether the neurovascular bundle had been excised, and whether tumor
was present in the bundle region. RESULTS: In 14 (17.5%) of 80 cases, excising
the neurovascular bundle led to a situation in which there was tumor in the
neurovascular bundle, all the surgical margins of resection were negative for
tumor, and there was no seminal vesicle or lymph node involvement. The remaining
cases were equally divided between (a) less aggressive tumors that were organ
confined or had only focal extraprostatic extension with no tumor in the
neurovascular bundle and (b) more aggressive tumors that had positive margins or
involvement of the seminal vesicles or lymph nodes. Within the latter group,
however, there were 9 patients (11.3% of all 80 cases) with negative seminal
vesicles and lymph nodes in whom excision of the neurovascular bundle at least
reduced the extent of positive margins. Most of the positive margins in patients
with tumor in the neurovascular bundle occurred outside the bundle region, and in
this study, none of the cases with positive surgical margins were the sole result
of failure to excise the neurovascular bundle. CONCLUSIONS: When perineural
invasion is seen on needle biopsy, the morbidity of resecting one or both
neurovascular bundles, which in some cases could turn out to be unnecessary, must
be weighed against the benefit of reducing the incidence of positive margins
(17.5% of our cases) or decreasing the extent of positive margins (11.3% of our
cases).
PMID- 10197852
TI - CUOG randomized trial of neoadjuvant androgen ablation before radical
prostatectomy: 36-month post-treatment PSA results. Canadian Urologic Oncology
Group.
AB - OBJECTIVES: To test the hypothesis that neoadjuvant androgen ablation before
radical prostatectomy reduces the likelihood of biochemical progression at 36
months. METHODS: Two hundred thirteen patients with localized prostate cancer
were randomized to radical prostatectomy alone (Sx, n = 101) or a 12-week course
of 300 mg of cyproterone acetate daily followed by surgery (CPA, n = 112).
Biochemical progression (two consecutive detectable prostate-specific antigen
[PSA] values) was determined for the entire group and by baseline PSA, Gleason
score, clinical stage, and pathologic stage. RESULTS: The probability of
biochemical progression at 36 months was similar in both groups (CPA 40.2%, Sx
30.1%; P = 0.3233). CPA patients with baseline serum PSA between 25 and 50 ng/mL
had a lower probability of biochemical progression (CPA 63.5%, Sx 84.6%; P =
0.0038). No difference in the probability of biochemical progression was seen
between groups when analyzed by clinical stage or Gleason score. When analyzed by
pathologic margin status, no difference was observed in the probability of
biochemical progression in patients with organ-confined disease (P = 0.4484).
There was a trend for a higher probability of progression in the neoadjuvant arm
in patients with positive and negative surgical margins (P = 0.0105, P = 0.0459;
alpha = 0.005 with Bonferroni adjustment). CONCLUSIONS: Neoadjuvant androgen
ablation with CPA reduces the positive margin rate significantly but does not
result in a difference in biochemical progression at 3 years. This may be due to
a lack of sufficient follow-up, insufficient power of the trial to demonstrate a
small benefit, or a true lack of benefit of neoadjuvant androgen ablation before
radical prostatectomy.
PMID- 10197853
TI - Prostate cancer detection: relationship to prostate size.
AB - OBJECTIVES: It has been suggested that the lower detection rate for cancer in
large prostates is due to the smaller proportion of tissue sampled. To examine
this hypothesis, we evaluated whole-mount radical prostatectomy specimens in
which the volume of cancer had been determined. We correlated cancer volume to
overall gland volume. In addition, we performed stochastic computer simulations
of parasagittal sextant biopsies on the same group of radical prostatectomy
specimens. We correlated the likelihood of a positive cancer biopsy simulation
with tumor volume and gland size. METHODS: Six hundred seven tumor foci from 180
serially sectioned whole-mount prostatectomy specimens were mapped and digitized.
Tumor volume was calculated by a step-section planimetry algorithm. Before
sectioning, each gland was weighed. Systematic parasagittal sextant biopsies were
computer simulated for each case. For each prostate, 40 simulations were
performed, with random variations in biopsy location programmed for each run.
Overall cancer detection by biopsy was considered positive if 90% of the 40
simulation runs were positive for cancer. Chi-square tests were used to evaluate
statistical significance. RESULTS: Small-volume cancers (0.5 cc or less) were
twice as frequent in large glands greater than 50 g (P = 0.03). These small
volume tumors comprised 33% (13 of 40) of cancers in prostates greater than 50 g,
16% (5 of 31) in glands less than 30 g, and 14% (15 of 109) in glands 30 to 50 g.
The rate of positive sextant biopsy simulation was lower in glands greater than
50 g than in glands 50 g or less (48% versus 67%, P<0.03). Smaller cancers were
much less likely to be detected in the simulations. The simulation detection rate
for cancers 0.5 cc or less was 18% (6 of 33), compared with a detection rate of
73% (107 of 147) for cancers greater than 0.5 cc (P<0.00001). CONCLUSIONS: The
observed lower cancer detection rate in large glands is a result of the higher
proportion of low-volume cancers in these glands. This suggests that large
prostates are more likely to be biopsied because of an elevated prostate-specific
antigen value resulting from benign elements of the gland and not from a
significant cancer. Increasing the number of cores solely to compensate for
increased prostate size risks a disproportionate increased detection of small
volume tumors with a low clinical likelihood of progression.
PMID- 10197854
TI - Prostate cancer histologic trends in the metropolitan Detroit area, 1982 to 1996.
AB - OBJECTIVES: One of the concerns regarding the widespread use of serum prostate
specific antigen (PSA) as a screening tool for prostate cancer is the possibility
that it may detect latent or clinically insignificant cancers. One indicator of
clinical importance is thought to be histologic grade, with clinically
unimportant cancers more likely to be well differentiated and clinically
important tumors more likely to be moderately or poorly differentiated. METHODS:
Data from the metropolitan Detroit population-based Surveillance, Epidemiology,
and End Results Program were examined to determine trends in prostate cancer
histologic grading before and after the introduction of PSA screening. RESULTS:
From 1989 through 1996, the most recent year for which data are available, a
dramatic increase in the incidence of prostate cancer occurred in the Detroit
area, corresponding to the routine use of PSA as a screening test for prostate
cancer. Local stage cancer demonstrated the largest increase in incidence. The
incidence of moderately differentiated cancers also rose substantially during the
same period; the incidence of poorly differentiated tumors remained about the
same, and the incidence of well differentiated tumors decreased. Coincident with
the increasing proportion of moderately differentiated cancers was a significant
increase in the proportion of prostate biopsies performed (P = 0.001).
CONCLUSIONS: These population-based data add important evidence that prostate
cancers identified with PSA are more likely to be moderately than well
differentiated. Additionally, if the definition of clinical significance depends
on histopathologic grade, this finding could further be interpreted as evidence
that PSA is more likely to detect clinically significant prostate cancer.
PMID- 10197855
TI - Efficacy of oral sildenafil in patients with erectile dysfunction after
radiotherapy for carcinoma of the prostate.
AB - OBJECTIVES: To determine the efficacy of sildenafil for patients with erectile
dysfunction after radiotherapy for localized prostate cancer. METHODS: Fifty
patients with erectile dysfunction after radiotherapy were treated with
sildenafil. Their median age was 68 years (range 54 to 78). All were treated with
a three-dimensional conformal external beam radiotherapy approach, and the median
dose prescribed to the planning target volume was 75.6 Gy. Patients were
initially given 50 mg of sildenafil and instructed to use the medication on at
least three occasions. They were then contacted to ascertain the efficacy of and
tolerance to the medication. RESULTS: Significant improvement in the firmness of
the erection after sildenafil was reported in 37 patients (74%), 2 (4%) had
partial improvement, and 11 (22%) had no response. Significant improvement in the
durability of the erection was reported in 33 patients (66%), 3 (6%) had partial
improvement, and 14 (28%) reported no improvement. Patients with partial or
moderate erectile function before using sildenafil were more likely to benefit
from the medication compared with those with absent function. Among 29 patients
with erections classified as partial after radiotherapy, 26 (90%) had a
significant response to the medication. In contrast, only 11 (52%) of 21 with
erections classified as flaccid after radiotherapy had a significant response to
the medication (P = 0.007). CONCLUSIONS: Sildenafil improved erectile function in
greater than two thirds of patients with postradiotherapy impotence. Patients
with less severe dysfunction are most likely to benefit from this intervention.
PMID- 10197856
TI - Venous malformation of the glans penis: efficacy of treatment with
neodymium:yttruim-aluminum-garnet laser.
AB - OBJECTIVES: Vascular anomalies in the urogenital tract are very rare and those
located in glans penis are the most uncommon. There is some controversy
concerning their nomenclature, diagnosis and treatment. We present an analysis of
our experience and a critical review of the literature. METHODS: Three cases of
vascular lesions in the glans penis concordant with venous malformations were
diagnosed at our center in 1996. The patients were 22, 20, and 12 years old, and
attended our center for aesthetic reasons only. Even though two of the lesions
were large, treatment with neodymium:yttrium-aluminium-garnet (Nd:YAG) laser
irradiation was used. RESULTS: The outcome of treatment was satisfactory and no
signs of recurrence were observed at follow-up examinations after a minimum of 18
months. CONCLUSIONS: Until recently, surgery has been the classical therapeutic
approach, and only a few cases treated with the Nd:YAG laser have been reported.
However, in our opinion, this should be the first choice treatment for this
anomaly, given its efficacy, cosmetic results, and low morbidity.
PMID- 10197857
TI - Iatrogenic prostatic urethral strictures: classification and endoscopic
treatment.
AB - OBJECTIVES: The treatment of posterior urethral strictures is a controversial
subject. For proper treatment, it is important to differentiate between
iatrogenic prostatic urethral strictures and post-traumatic membranous urethral
strictures. METHODS: Iatrogenic strictures of the prostatic urethra have been
classified according to location and etiology into three categories: type I,
located exclusively at the bladder neck; type II, located in the midportion of
the prostatic fossa; and type III, when the whole prostatic fossa is replaced by
stricture. From 1970 to 1996, 163 patients with postoperative strictures of the
prostatic urethra were treated endoscopically. RESULTS: The results obtained in
122 patients are reported; 41 patients are not evaluable. The median follow-up
was 63 months (range 12 to 239). Seven patients required a second endoscopic
procedure to attain cure. Good results were achieved in 54 (91%) of 59 patients
with type I strictures, in 45 (98%) of 46 patients with type II strictures, and
in 13 (76%) of 17 patients with type III strictures. The overall success rate was
92% (112 of 122). Complications occurred in 21 patients (17%), including
postoperative urinary tract infection (11%), incontinence (4%), stress
incontinence (1%), and severe bleeding (1%). CONCLUSIONS: Postoperative
strictures of the prostatic urethra must be recognized and can be easily treated
with endoscopic therapy.
PMID- 10197858
TI - Iontophoresis as a new method of delivering local anesthesia to the urethra: a
pilot study.
AB - OBJECTIVES: To test the feasibility of using the iontophoretic catheter as a
means of delivering local anesthetic (lidocaine hydrochloride) to the urethra for
periurethral injection of collagen. METHODS: Eight women with urodynamically
proven genuine stress incontinence underwent periurethral collagen injections.
Local anesthesia was provided by 4% lidocaine with 1 in 100,000 epinephrine
administered over 10 minutes using an iontophoretic catheter. Pain was assessed
by Likert and visual analogue scales. Cystoscopic appearance of the urethra was
noted. RESULTS: The periurethral bulking procedure was completed without further
anesthetic in 7 women, 1 of whom had no pain. There was no evidence of urethral
damage from the iontophoresis. CONCLUSIONS: Iontophoresis shows promise as a
method of providing analgesia to the urethra. However, the degree of analgesia is
variable, and further research is needed on catheter design to ensure transport
of anesthetic agent into the periurethral tissues.
PMID- 10197859
TI - EDITS: development of questionnaires for evaluating satisfaction with treatments
for erectile dysfunction.
AB - OBJECTIVES: To develop Patient and Partner versions of a psychometrically sound
questionnaire, the EDITS (Erectile Dysfunction Inventory of Treatment
Satisfaction), to assess satisfaction with medical treatments for erectile
dysfunction. METHODS: Treatment satisfaction differs from treatment efficacy as
it focuses on a person's subjective evaluation of treatment received. Twenty-nine
items representing the domain of treatment satisfaction for men and 20
representing partner satisfaction were generated. Two independent samples of 28
and 29 couples completed all items at two points in time. Spearman rank-order
correlations were derived to assess test-retest reliability and couple
coefficients of validity. Internal consistency coefficients were calculated for
both Patient and Partner versions and a content validity panel was used to
analyze content validity. RESULTS: Only items that met all the following criteria
were selected to comprise the final questionnaires: (a) range of response four or
more out of five; (b) test-retest reliability greater than 0.70; (c) ratings by
at least 70% of the content validity panel as belonging in and being important
for the domain; and (d) significant correlation between the subjects' and
partners' responses. Eleven patient items met criteria and formed the Patient
EDITS; five partner items met criteria and formed the Partner EDITS. Scores on
the two inventories were normally distributed with internal consistencies of 0.90
and 0.76, respectively. Test-retest reliability for the Patient EDITS was 0.98;
for the Partner EDITS, it was 0.83. CONCLUSIONS: Reliability and validity were
well established, enabling the EDITSs to be used to assess satisfaction with
treatment modalities for erectile dysfunction and to explore the impact of
patient and partner satisfaction on treatment continuation.
PMID- 10197860
TI - Sildenafil citrate (Viagra) in erectile dysfunction: near normalization in men
with broad-spectrum erectile dysfunction compared with age-matched healthy
control subjects.
AB - OBJECTIVES: To evaluate the efficacy, safety, and tolerability of sildenafil in
men with broad-spectrum erectile dysfunction (ED), with reference to age-matched
healthy control subjects. METHODS: One hundred eleven patients were enrolled in a
randomized, double-blind, placebo-controlled, parallel-group, 12-week, flexible
dose study. Efficacy assessments included the International Index of Erectile
Function (IIEF), a global assessment question, and patient event log data. In a
separate, nontreatment study, 109 control subjects also completed the IIEF.
RESULTS: Mean IIEF scores at baseline were significantly lower for patients with
ED than for control subjects without a history of ED. After treatment, mean IIEF
scores for patients receiving sildenafil approached values observed in control
subjects and were significantly higher than mean scores for patients receiving
placebo (P<0.01). Responses to the global assessment question and patient log
data corroborated the IIEF results. Sildenafil was well tolerated, with no
discontinuations because of adverse events. CONCLUSIONS: The results indicate
that sildenafil, an effective oral therapy for the treatment of broad-spectrum
ED, is associated with a near normalization of patient erectile function.
PMID- 10197861
TI - Increased incidence of testicular cancer in active duty members of the Department
of Defense.
AB - OBJECTIVES: Multiple reports have noted an increase in testicular cancer
incidence in virtually all world populations. We sought to determine whether an
increase in testicular cancer incidence has occurred in active duty members of
the Department of Defense (DOD). METHODS: The total number of tumors accessioned
at all DOD tumor registries, encompassing virtually all tumors diagnosed in
active duty personnel, was obtained from the centralized DOD tumor registry. The
number of men on active duty in the DOD was obtained from the Defense Manpower
Data Center. RESULTS: The rate of testicular cancer increased from 8.62/100,000
active duty men in 1988 to 15.38/100,000 in 1996. CONCLUSIONS: These data
corroborate observations from multiple other populations that the incidence of
testicular cancer is increasing. The explanation for this observation is unknown.
PMID- 10197862
TI - Positron emission tomography in the clinical staging of patients with Stage I and
II testicular germ cell tumors.
AB - OBJECTIVES: To evaluate the accuracy of fluorodeoxyglucose positron emission
tomography (PET) compared with computed tomography (CT) staging in patients with
Stage I and II testicular germ cell tumors (GCTs). METHODS: From January 1995 to
July 1997, in 37 patients with clinical Stage (CS) I (n = 25) and CS II (n = 12)
GCT (24 nonseminomas, 13 seminomas), PET and CT were compared in the initial
staging. After PET, the patients with nonseminomatous GCT were staged surgically
by retroperitoneal lymph node dissection and the patients with seminomatous GCT
were followed up clinically. RESULTS: Correct staging by PET was achieved in 34
of 37 patients compared with correct CT staging in 29 of 37 patients. Of 10
metastatic lesions, 7 and 4 were detected by PET and CT, respectively. PET did
not show false-positive signals. PET was unable to detect vital cancer with a
maximal diameter less than 0.5 cm or teratoma at any size. CONCLUSIONS: PET was
useful for detecting viable tumor in lesions that are visible on CT scan and,
thus, it may omit false-positive CS II lesions. However, PET was not able to
identify mature teratoma. In this study, PET did not improve the staging in
patients with CS I tumor.
PMID- 10197863
TI - Contemporary incidence of morbidity related to vesicoureteral reflux.
AB - OBJECTIVES: The association among vesicoureteral reflux (VUR), renal scarring,
and reflux nephropathy is well established. Screening programs for children who
present with urinary tract infection (UTI) and their siblings, along with medical
and surgical management, have been promoted by pediatric medical and urologic
specialists in Buffalo and the surrounding community for more than two decades.
Has this comprehensive and costly effort resulted in a decrease in VUR-related
morbidity and should it be continued? METHODS: The records of all active patients
who presented from 1982 through 1997 to this region's single pediatric nephrology
referral center were reviewed. One hundred twenty-two children and adolescents
(73 boys, 49 girls) were identified with hypertension (HTN), renal insufficiency
(RI), and end-stage renal disease (ESRD) requiring dialysis or transplantation.
RESULTS: There were 70 patients (57%) with HTN, 19 (16%) with RI, and 33 (27%)
with ESRD. Reflux nephropathy was the underlying cause in 6 patients (5%)-3 with
HTN and 3 with ESRD. The etiologies of morbidity in the remaining patients were
medical renal disease, 61 (50%); idiopathic, 17 (14%); obstructive uropathy, 14
(11%); primary congenital renal hypoplasia, 12 (10%); and vascular, 12 (10%). Of
the 6 patients with VUR-related morbidity, 4 were boys (3 with ESRD, 1 with HTN)
and 2 were girls (with HTN). Five children presented in the 1980s and 1 in the
1990s. Only 1 patient had a history of UTI, and she presented early in the series
in 1982 at 5 years of age. Ages of presentation were infancy (2 boys), early
childhood (1 boy, 1 girl), and adolescence (1 boy, 1 girl). Reasons for
presentation were failure to thrive (n = 2), voiding dysfunction without UTI (n =
1), muscle cramps (n = 1), UTI (n = 1), and HTN (n = 1). Reflux grade ranged from
I to V, but 4 patients had grade III or less. CONCLUSIONS: Awareness of VUR
related morbidity has led to more widespread diagnosis and treatment, which
appears to have resulted in a dramatic decrease in the numbers of affected
patients in this community. The diagnosis and treatment of VUR has altered the
epidemiology of HTN and renal failure in children and young adults.
PMID- 10197864
TI - Preliminary results of percutaneous treatment of renal cysts with povidone-iodine
sclerosis.
AB - Symptomatic renal cysts can be treated with percutaneous sclerosis using ordinary
povidone-iodine solution. We describe our methods and outcomes in 5 patients so
treated.
PMID- 10197865
TI - Images in clinical urology. Magnetic resonance imaging of a "saddle bag" urethral
diverticulum.
PMID- 10197866
TI - Images in clinical urology. Scrotal lymphangioma in an adult.
PMID- 10197867
TI - Perineal approach to radical prostatectomy in kidney transplant recipients with
localized prostate cancer.
AB - Close urologic follow-up of renal transplant candidates and recipients often
reveals prostate carcinoma at an early stage. Two patients who underwent renal
transplantation for end-stage disease also underwent radical perineal
prostatectomy for localized prostate carcinoma, 3 years after grafting in 1
patient and 4 years before grafting in the other. The perineal approach to
prostatectomy may facilitate later renal transplantation and avoid allograft
damage.
PMID- 10197868
TI - Hydronephrosis in pregnancy: simultaneous depiction of fetal and maternal
hydronephrosis by magnetic resonance urography.
AB - Magnetic resonance urographic (MRU) techniques possess image quality and
diagnostic capability that are improving with increasingly sophisticated imaging
sequences and shorter scanning times. We describe the application of a fast
breath-hold MR sequence (HASTE) in the assessment of ureteric obstruction in
pregnancy. In the patient presented, HASTE MRU was successful in depicting
ureteral anatomy and demonstrated dilation of both ureters below the level of the
pelvic brim. This observation suggested distal ureteral obstruction rather than
simple hydronephrosis of pregnancy. As a result, bilateral nephrostomies were
performed and neonatal prematurity was avoided. Interestingly, in this patient,
HASTE MR imaging also showed evidence of concurrent fetal hydronephrosis.
PMID- 10197869
TI - Interstitial microwave thermoablation for localized prostate cancer.
AB - The conventional treatment for localized prostate cancer can be associated with
significant morbidity and cost. Interstitial microwave thermoablation is a
minimally invasive procedure used experimentally to treat selected patients with
failed radiation therapy of prostate cancer at our institution. Preliminary
results in these patients suggest that this treatment might be a useful
alternative in selected patients with previously untreated localized prostate
cancer. In this report we describe the first use of percutaneous transperineal
interstitial microwave thermoablation to treat a case of primary prostate cancer.
There were no treatment complications. At 18 months the patient's serum prostate
specific antigen remains undetectable, and his prostate biopsy shows no evidence
of malignancy. These very preliminary but exciting results in this single patient
suggest that this experimental technique should be explored further.
PMID- 10197870
TI - Adenosquamous carcinoma of the prostate: case report with DNA analysis,
immunohistochemistry, and literature review.
AB - We diagnosed prostatic adenosquamous carcinoma by prostate core needle biopsy in
a 55-year-old man with no history of prostate cancer. The prognosis, DNA
analysis, and histogenesis of this extremely rare tumor are controversial. To our
knowledge, this is the first case of adenosquamous carcinoma diagnosed by core
needle biopsy in a patient with no history of prostate cancer or hormonal
therapy. We performed immunohistologic and DNA analysis to further characterize
this cancer. The clinical presentation and abnormal DNA analysis portend an
aggressive course.
PMID- 10197871
TI - Now what do we do with all these genes? Yeast-based two-hybrid analysis: an
emerging technology for molecular urology in the post-genome era.
AB - By the year 2005, the Human Genome Project is expected to have mapped and
sequenced all of the estimated 100,000 genes that encode the various proteins
found in human cells. Defining the role of each gene, and using that information
to redirect its action when therapeutic intervention is required, is one of the
major assignments for molecular medicine and molecular urology in the post-genome
era. This challenge to determine gene function, and to do it cost-effectively and
on a large scale, has driven development of new technologies that can more
efficiently flag genes that are likely targets for therapeutic intervention.
Yeast-based genetic assays that detect protein-protein interactions in vivo offer
many of the features required of a practical "gene-flagging" strategy for
identifying genes that might be functionally manipulated to achieve therapeutic
goals. In the past few years, the yeast-based assays collectively referred to as
"two-hybrid interaction traps" or simply "two-hybrid systems" have become
increasingly important tools for experimental analysis of gene function. This
review presents an overview of the principles of yeast-based two-hybrid analysis,
examines some specific applications of the technique of interest to urologic
investigators, and discusses some key points that a basic urologic investigator
new to the technology would want to consider when designing or evaluating a yeast
based two-hybrid project.
PMID- 10197873
TI - Endogenous carbohydrate-binding proteins of rabbit and human bladder.
AB - OBJECTIVES: To identify the endogenous lectins of the human bladder with the long
term goal of developing improved strategies for the treatment of interstitial
cystitis and other bladder disorders. METHODS: Rabbit and human bladder sections
were examined histochemically using biotinylated neoglycoconjugates. Affinity
chromatography of extracts of rabbit bladder was performed on immobilized lactose
to purify the galactose-binding protein. RESULTS: Biotinylated beta-D-galactose
neoglycoconjugate showed the strongest specific staining of the rabbit and human
bladder sections. The beta-D-N-acetylglucosamine neoglycoconjugate also showed
significant staining; the alpha-L-fucose, alpha-D-mannose, alpha-D-N
acetylneuraminic acid, and alpha-D-N-acetylgalactosamine neoglycoconjugates
showed either very weak or no reaction. The strong Ca2+ -independent binding of
beta-D-galactose neoglycoconjugates suggested the presence of galectins in rabbit
and human bladder. Affinity chromatography of rabbit bladder extract on lactose
gel yielded a galectin of about 30 kDa, consistent with the molecular biological
data confirming the expression of galectin-3 in bladder. CONCLUSIONS: Beta-D
galactose binds strongly and specifically to rabbit and human bladder tissue
sections. This information would be useful for the purpose of modifying drugs
used for the treatment of bladder disorders with ligands of galactose-binding
lectins to improve their retention in the bladder.
PMID- 10197872
TI - Expression of MAGE genes in testicular germ cell tumors.
AB - OBJECTIVES: Some of the MAGE gene family that encode tumor-rejection antigens
recognized by cytotoxic T lymphocytes are expressed at the mRNA level in various
malignant tumors. However, these genes are silent in normal tissues, except in
the testis and placenta. It is therefore important to understand how MAGE gene
expression changes with malignant transformation of the testis. We investigated
the expression of MAGE-1, -2, -3, and -4 genes at the mRNA level in testicular
germ cell tumors. METHODS: Reverse transcriptase-polymerase chain reaction for
MAGE genes was performed using 32 testicular germ cell tumor specimens. RESULTS:
MAGE-1, -2, -3, and -4 mRNA was detected in 16 (72%), 15 (68%), 18 (82%), and 17
(77%) of 22 patients with pure seminoma or mixed type with seminomatous elements.
MAGE-1 , -2, -3, and -4 mRNA was found in 2 (20%), 5 (50%), 4 (40%), and 4 (40%)
of 10 patients with nonseminomatous germ cell tumor (NSGCT). The expression rate
of MAGE-1, -3, and -4 mRNA was significantly higher in patients with seminomatous
elements than that in those with NSGCT. MAGE expression did not correlate with
disease progression. CONCLUSIONS: MAGE genes are more preserved in seminoma than
in NSGCT. This suggests that seminoma has traits more similar to normal testis
than does NSGCT.
PMID- 10197874
TI - Near-infrared confocal laser scanning microscopy of bladder tissue in vivo.
AB - OBJECTIVES: To assess the potential of a near-infrared confocal laser scanning
microscope (CLSM) for imaging bladder tissue in vivo. METHODS: Confocal images of
the exposed bladder of male Sprague-Dawley rats were obtained with a CLSM. To
minimize tissue motion, the bladder was placed in light contact under an
objective lens housing, and the top surface was lightly flattened with a
coverslip. Images were obtained from the outer and inner layers of the bladder
wall with a lateral resolution of 0.5 to 1 microm and an axial resolution
(section thickness) of 3 to 5 microm. The confocal images were later correlated
with routine histologic studies. RESULTS: The CLSM allows imaging of the
urothelium, the superficial and deep portions of the lamina propria, the
muscularis propria, and the serosa of the bladder wall in vivo. Urothelial cells,
collagen bundles and fibers, muscle, and circulating blood cells in capillaries
and larger blood vessels are easily visualized. The confocal images correlated
well with the histologic studies. CONCLUSIONS: Confocal microscopy allows real
time, high-resolution, high-contrast imaging of cellular and structural
morphologic features to a maximal depth of 300 microm within the bladder wall in
vivo. Artifacts caused by tissue motion can be minimized with a bladder-objective
lens contact housing.
PMID- 10197876
TI - Clinical aspects of vasectomy.
PMID- 10197875
TI - Genitourinary surgery and Arthur Jacobs: father of urology in Glasgow.
AB - Arthur Jacobs (1899-1974) was the father of urology in Glasgow. His extensive
experience with genitourinary tuberculosis, ureterosigmoidostomy, and bladder
augmentation were far ahead of his time. He became an expert in retropubic
prostatectomy and was a pioneer in early imaging techniques.
PMID- 10197877
TI - Long-term use of pentosan polysulfate for interstitial cystitis.
PMID- 10197878
TI - Digital rectal examination and mortality from prostate cancer.
PMID- 10197880
TI - Mental health and Maori development.
AB - OBJECTIVE: The objective of this paper is to illustrate trends in Maori health,
examine earlier health policies and to suggest avenues for improved mental
health. METHOD: Several sources of historical and contemporary data have been
reviewed and there has been some analysis of mental health policies as they
relate to Maori. The interplay between culture, socioeconomic circumstances and
personal health has been used as a context within which strategic directions are
discussed. RESULTS: Five strategies are highlighted: the promotion of a secure
cultural identity, active Maori participation in society and the economy,
improved mental health services, workforce development, autonomy and control. It
is recommended that mental health services should be more closely aligned with
primary health care, Maori youth, Maori-centred frameworks, and evidence-based
practices. CONCLUSIONS: Improvements in Maori mental health require broad
approaches which are consistent with Maori aspirations and coordinated across the
range of sectoral and disciplinary interests. Active Maori participation in the
process and the retention of a cultural base will be critical if the current
trends are to be reversed.
PMID- 10197879
TI - Prostate-specific antigen levels after radical prostatectomy versus
brachytherapy.
PMID- 10197881
TI - Chinese migrants' mental health and adjustment to life in New Zealand.
AB - OBJECTIVE: The purpose of this study was to identify and assess the relative
importance of predictors of the self-rated adjustment and psychiatric morbidity
of recent Chinese migrants. METHOD: Chinese migrants (n = 271) living in Auckland
and aged 15 years or older completed a postal questionnaire that included the
Chinese Health Questionnaire (CHQ). The majority of respondents came from Hong
Kong and Taiwan. RESULTS: Most respondents did not report major adjustment
problems. The psychiatric morbidity rate was 19%. Major predictors of
experiencing problems included rejection by locals, being aged 26-35 years or
over 45 years and low English proficiency. Major predictors of poor adjustment
included unemployment, low English proficiency, lack of university education,
younger age, shorter residency, expectations not met and regrets about coming to
New Zealand. Predictors of minor mental disorder included regretting coming,
female gender and younger age. For migrants resident 2 years or less,
unemployment and underemployment were additional risk factors. Mothers with
absent husbands and young people with absent parents also had elevated rates of
mental disorder. CONCLUSIONS: Although the overall prevalence of mental disorder
for this sample of recent migrants appears to be similar to that of the general
population, significant risk factors were identified. The findings extend
knowledge of the adjustment and the mental health of migrants and provide
potential focal points for primary and secondary prevention interventions.
PMID- 10197882
TI - Parental satisfaction and outcome: a 4-year study in a child and adolescent
mental health service.
AB - OBJECTIVE: The aim of this paper is to examine the facets of parental
satisfaction and its relationship with clinician-rated outcome in a child and
adolescent mental health service. METHOD: Patients (n = 1278) consecutively
assessed between 1992 and 1996 were included in the study. When treatment ended,
clinicians rated the outcome of the intervention and parents were asked to
complete a satisfaction questionnaire. RESULTS: Sixty-nine per cent of cases were
rated by clinicians as having a positive outcome. Outpatients were more likely to
be given a positive rating than inpatients. Satisfaction questionnaires were
returned by 40% of parents; 76% of these were mostly or very satisfied.
Satisfaction scores increased with the number of outpatient sessions attended but
did not differ between inpatients and outpatients. There was a significant but
small agreement (27% better than chance) between clinicians' rating of outcome
and parental satisfaction. Level of agreement varied according to service
provided and the number of sessions attended. While rates of positive outcome
increased over the study period, ratings of satisfaction were stable.
CONCLUSIONS: Overall, ratings of satisfaction were comparable with those reported
in other studies. Variations in concordance between parents and clinicians show
that outcome and satisfaction, although related, are different constructs
influenced by different factors depending on the services provided. Focusing on
specific aspects of satisfaction, as opposed to global measures, may be more
useful for services, although such undertakings must be supported with efforts to
improve clinical outcomes.
PMID- 10197883
TI - Children who are cruel to animals: a revisit.
AB - OBJECTIVE: There is a paucity of research regarding children who are cruel to
animals (CTA). Previous studies have suggested that being CTA is linked with
recurrent aggression in adulthood. In this report, children with persistent
conduct problems who are CTA are examined. METHOD: A clinic-referred sample of
141 children and a community sample of 36 children between the ages of 5-12 were
assessed using a test battery of questionnaires for parents, teachers and the
child on mental health symptoms, self-perception, demographics and psychosocial
factors. Forty of the clinic-referred children and one of the community group
were rated by their parents as sometimes or definitely cruel to animals. The CTA,
non-CTA and community samples were compared. RESULTS: The CTA group had more
conduct symptoms compared with the non-CTA group. However, the older CTA group
unexpectedly reported a higher self-esteem compared with the non-CTA group. There
was no significant difference between the two clinic-referred groups in gender,
attention deficit hyperactivity disorder and internalising symptoms, and
psychosocial factors. CONCLUSION: Being CTA is possibly a marker of a subgroup of
conduct disorder which has a poor prognosis.
PMID- 10197884
TI - Trauma-induced dissociative amnesia in World War I combat soldiers.
AB - OBJECTIVE: This study relates trauma-induced dissociative amnesia reported in
World War I (WW I) studies of war trauma to contemporary findings of dissociative
amnesia in victims of childhood sexual abuse. METHOD: Key diagnostic studies of
post-traumatic amnesia in WW I combatants are surveyed. These cover phenomenology
and the psychological dynamics of dissociation vis-a-vis repression. RESULTS:
Descriptive evidence is cited for war trauma-induced dissociative amnesia.
CONCLUSION: Posttraumatic amnesia extends beyond the experience of sexual and
combat trauma and is a protean symptom, which reflects responses to the gamut of
traumatic events.
PMID- 10197885
TI - How is psychiatry taught to Australian and New Zealand medical students?
AB - OBJECTIVE: This study aimed to describe the amount, format and content of
psychiatry teaching programs in all 12 Australian and New Zealand medical
schools. METHOD: A structured questionnaire which included definitions and coding
instructions was completed by class coordinators for the years of 1995 or 1996.
Missing and inconsistent data were checked by coordinators and results were
confirmed by heads of department. RESULTS: Most departments of psychiatry taught
throughout the undergraduate course. Only three made no contribution to pre
clinical teaching. The time devoted to clinical tuition ranged from 279 to 454 h
per university with a mean of 353 h. Clinical attachments occupied most time
(mean = 70%), followed by small group teaching (mean = 19%) and lectures (mean =
11%). Medical schools varied greatly in the attention given to history taking and
mental state examination, psychological therapies and the sub-specialties of
child and aged psychiatry. Clinical attachments were mostly to adult inpatient
units. Private psychiatric hospitals and clinics were used infrequently as were
consultation-liaison psychiatry services and primary care. CONCLUSION: There is a
need to broaden the clinical experience of students to better equip them for
future medical practice. There appears to be a serious mis-match between the
settings in which most students are taught and the settings in which most will
work later as non-psychiatric practitioners. It was disappointing that
psychological therapies received so little attention given the central place of
counselling in modern medical practice.
PMID- 10197886
TI - Mental health triage in emergency medicine.
AB - OBJECTIVE: The aim of this study was to: (i) develop a triage scale consistent
with the National Triage Scale (NTS) for patients with mental health problems
attending emergency departments; and (ii) to reduce emergency waiting times,
transit times and improve skills assessing mental health problems. METHOD: We
developed a Mental Health Triage Scale (MHTS) consistent with the NTS. The MHTS
was then implemented using a structured education package, and evaluated from
March to August 1994. Further evaluation occurred after 2 years. RESULTS: A four
tiered MHTS was produced: category 2, violent, aggressive or suicidal, danger to
self or others or with police escort; category 3, very distressed or psychotic,
likely to deteriorate, situational crisis, danger to self or others; category 4,
long-standing semi-urgent mental health disorder, supporting agency present; and
category 5, long-standing non-acute mental health disorder, no support agency
present. Patients with illness, injury or self-harm were triaged using combined
mental health and medical information. Mean emergency waiting times and transit
times were reduced. More consistent triaging for mental health patients occurred,
and more consistent admission rates by urgency. Reduced mental health 'did not
waits' showed improved customer satisfaction. Mental Health Triage Scale was
considered appropriate by liaison psychiatry and its use has continued at 2 years
follow-up. CONCLUSIONS: A systematic approach to mental health triaging produced
a workable scale, reduced waiting times, transit times, and provided effective
and consistent integration of mental health patients into a general emergency
department.
PMID- 10197887
TI - Pre-existing antidepressant medication and the outcome of group cognitive
behavioural therapy.
AB - OBJECTIVE: This study aimed to investigate the impact of pre-existing medication
on the outcome of group cognitive-behavioural therapy (CBT) in the treatment of
patients with depression. METHOD: Of the 71 patients diagnosed with major
depression who participated in group CBT, 25 were on medication (CBT-M) and 46
were unmedicated (CBT). The patients received 12 sessions of group CBT over a 3
month period. The dependent measures used were the Beck Depression Inventory,
Zung Self-Rating Depression Scale, Automatic Thoughts Questionnaire, Hopelessness
Scale, Dysfunctional Attitude Scale, Daily Activity Rating Scale and Daily Mood
Rating Scale. RESULTS: Both the CBT and CBT-M groups showed statistically
significant improvement in depression scores and cognitive process measures.
However, the rate of improvement for both groups on these measures did not
differ. CONCLUSION: The study indicated that pre-existing antidepressant
medication did not enhance or detract from the positive treatment outcome of
depressed patients receiving a group CBT treatment.
PMID- 10197888
TI - Attitudes towards people with a mental disorder: a survey of the Australian
public and health professionals.
AB - OBJECTIVE: The aim of this paper was to compare the Australian public's attitudes
towards people who have been treated for a mental disorder with the attitudes of
general practitioners, psychiatrists and clinical psychologists. METHOD: The
study involved a household survey of 2031 members of the Australian public and a
postal survey of 872 general practitioners, 1128 psychiatrists and 454 clinical
psychologists. Survey participants were presented with a vignette describing a
person with schizophrenia or one with depression. They were asked opinions about
the person's long-term outcome in various areas of life after receiving
treatment. Participants were also asked whether they thought the person described
would be discriminated against by others. RESULTS: Both the public and
professionals rated outcomes as poorer and discrimination as more likely for the
person with schizophrenia than for the one with depression. The professionals
made more negative ratings than the public, although the clinical psychologists
had similar attitudes to the public about depression. CONCLUSIONS: Compared to
the public, health professionals rate long-term outcomes more negatively and
discrimination as more likely. It is possible that these more negative attitudes
are realistic, being based on greater knowledge of mental disorders. However,
professional attitudes may be biased by greater contact with patients who have
chronic or recurrent disorders. Either way, health professionals need to be aware
of the effects that their negative attitudes might have on patients and the
public.
PMID- 10197889
TI - Megavitamin and dietary treatment in schizophrenia: a randomised, controlled
trial.
AB - OBJECTIVE: The aim of this study was to assess the efficacy of adjunctive
megavitamin and dietary treatment in schizophrenia. METHOD: A random allocation
double-blind, controlled comparison of dietary supplement and megavitamin
treatment, and an alternative procedure was given for 5 months to 19 outpatients
with a diagnosis of schizophrenia. In addition to usual follow-up, the
experimental group received amounts of megavitamins based on their individual
serum vitamin levels plus dietary restriction based on Radioallergosorbent (RAST)
tests. The control group received 25 mg vitamin C and were prescribed substances
considered allergenic from the RAST test. RESULTS: Five months of treatment
showed marked differences in serum levels of vitamins but no consistent self
reported symptomatic or behavioural differences between groups. CONCLUSIONS: This
study does not provide evidence supporting a positive relationship between
regulation of levels of serum vitamins and clinical outcome in schizophrenia over
5 months.
PMID- 10197890
TI - Amphetamine withdrawal: I. Reliability, validity and factor structure of a
measure.
AB - OBJECTIVE: The aim of this study was to create a short, reliable and valid
questionnaire for the evaluation of amphetamine withdrawal, which we shall call
the Amphetamine Withdrawal Questionnaire (AWQ). METHOD: Items of the AWQ included
in this study were based on the fourth edition of the Diagnostic and Statistical
Manual for Mental Disorders (DSM-IV) and a comprehensive review. A field trial
for assessing the reliability, validity and factor structure was conducted in
outpatients and inpatients with amphetamine withdrawal. RESULTS: Thirty and 102
patients' data were included in the reliability-validity tests and the factor
study, respectively. Due to the very low mean score of insomnia item, this item
was excluded from subsequent analyses. The AWQ internal consistency was
satisfactory with a Cronbach's alpha of 0.77. For test-retest reliability, a
Spearman rank order correlation coefficient of the AWQ total score was 0.79. The
AWQ total score for criterion validity was moderately correlated with the other
two accepted measures. Principal component analysis, eigenvalue-one test and a
varimax rotation performed to elicit the factors of AWQ yielded a three-factor
model of AWQ: namely hyperarousal, reversed vegetative and anxiety factors.
CONCLUSIONS: The AWQ is a short, reliable and valid measure for assessing
amphetamine withdrawal symptoms. Further studies with a larger number of patients
should be conducted to confirm the results of this factor analysis.
PMID- 10197891
TI - Amphetamine withdrawal: II. A placebo-controlled, randomised, double-blind study
of amineptine treatment.
AB - OBJECTIVE: The aim of this study was to examine the benefits of amineptine, a
dopamine agonist antidepressant, in treating amphetamine withdrawal. METHOD:
Inpatients with amphetamine withdrawal were recruited to participate in this
placebo-controlled, randomised, double-blind, parallel group, 2-week comparison
of amineptine and placebo treatments. The treatment effects were evaluated by
means of the self-administered Amphetamine Withdrawal Questionnaire (AWQ) and the
interviewer-administered Clinical Global Impression (CGI) scale. An intention-to
treat analysis was applied to evaluate the therapeutic effects at the end of week
1 and week 2. RESULTS: Twenty-two patients took part in each treatment group. The
week-1 and week-2 intention-to-treat analyses showed that the mean AWQ reversed
vegetative scores (combined scores of decreased energy, increased appetite and
craving for sleep items) of the amineptine group were significantly lower than
those of the placebo group. The general condition of the amineptine group
assessed by CGI also significantly improved at the end of week 2. Although the
discontinuation rate due to dissatisfaction with treatment of amineptine group
(1/21) was much lower than that of placebo group (6/22), those rates were not
significantly different (p = 0.09). CONCLUSIONS: Amineptine is specifically
effective for treating a major component of amphetamine withdrawal: a reversed
vegetative syndrome. Although more than 2 weeks of amineptine treatment may
contribute further benefits, both risks and benefits should be taken into account
in doing so.
PMID- 10197892
TI - Fluvoxamine-methadone interaction.
AB - OBJECTIVE: The aim of this paper is to report a case of symptomatic methadone
toxicity associated with fluvoxamine treatment. CLINICAL PICTURE: A 28-year-old
woman was admitted to hospital with severe hypoxaemia and hypercapnia indicating
hypoventilation. Medication prior to admission had been stable and included
methadone 70 mg daily and diazepam 2 mg twice daily. Three weeks before admission
she had commenced treatment with fluvoxamine. TREATMENT: Methadone was decreased
to 50 mg daily and diazepam was tapered to zero. OUTCOME: The serum methadone
concentration decreased and oxygenation improved considerably. CONCLUSIONS:
Clinicians should be aware of the potential for a significant drug interaction
between fluvoxamine and methadone.
PMID- 10197893
TI - Posttraumatic stress disorder, dissociative fugue and a locator beacon.
AB - OBJECTIVE: The aim of this paper is to report an aspect of the management of a
case of dissociative fugue. CLINICAL PICTURE: A Vietnam veteran was suffering
post-traumatic stress disorder. TREATMENT: Treatment involved the provision of a
locator beacon worn in a neck chain. OUTCOME: This treatment resulted in the
curtailment of the dissociative fugue episodes. CONCLUSION: The locator device
proved a useful component of a multimodal treatment regime.
PMID- 10197895
TI - Delusion of pregnancy.
PMID- 10197894
TI - Pathological jealousy appearing after cerebrovascular infarction in a 25-year-old
woman.
AB - OBJECTIVE: To report pathological jealousy (Othello syndrome) occurring in a
young woman with a right hemisphere cerebrovascular infarction and to review
diagnosis and possible organic mechanisms for the generation of this syndrome.
CLINICAL PICTURE: A 20-year-old woman was admitted to hospital with a right
hemisphere stroke associated with a history of severe migraine and the use of
oral contraceptives. The patient made a good recovery with minimal neurological
deficits but 5 years later developed the syndrome of morbid jealousy with
depression and a near fatal overdose. TREATMENT AND OUTCOME: Morbid jealousy
subsided, almost completely disappearing over a 6-week period of treatment with a
selective serotonin re-uptake inhibitor (SSRI). CONCLUSIONS: Case reports of the
Othello syndrome and other content specific delusions following right hemisphere
cerebrovascular infarction have appeared in geriatric psychiatry literature. The
occurrence of a similar association in a young patient lends support to the
suggestion of a causal relationship and has implications for diagnosis, clinical
care and research.
PMID- 10197896
TI - Dysrhythmia associated with clozapine.
PMID- 10197897
TI - Sex, lies and training programs: the ethics of consensual sexual relationships
between psychiatrists and trainee psychiatrists.
PMID- 10197898
TI - Clozapine-induced diabetic ketoacidosis.
PMID- 10197899
TI - Response to letter of Professor Tim Lambert.
PMID- 10197900
TI - Report of a rare medical complication on clozapine.
PMID- 10197901
TI - Impaired transverse patterning in human amnesia is a special case of impaired
memory for two-choice discrimination tasks.
AB - Three amnesic patients with damage limited to the hippocampal formation, a
severely amnesic patient with extensive medial temporal lobe damage, and 9
controls were tested on the transverse patterning problem (A + B-, B + C-, and C
+ A-) and also on 2 control problems. One of the control problems was matched to
the transverse patterning problem with respect to the number of pairwise
decisions that were required. The 2nd control problem was matched to the
transverse patterning problem with respect to the number of trials needed by
controls to learn the task. The amnesic patients were impaired at solving both
the transverse patterning problem and the control problems. The findings suggest
that impaired learning of the transverse patterning problem by amnesic patients
derives from their general impairment in declarative memory, which affects
performance on most 2-choice discrimination tasks.
PMID- 10197902
TI - Temporal discrimination learning in severe amnesic patients reveals an alteration
in the timing of eyeblink conditioned responses.
AB - This study investigated whether the hippocampal system plays a modulatory role in
the timing of conditioned responses (CRs) in eyeblink classical conditioning.
Seven bitemporal amnesic patients and 7 controls were randomly presented 2 tone
conditioned stimuli (CSs) that were individually paired with two different
interstimulus intervals (ISIs) in a delay conditioning task. It was found that
amnesic patients' CRs occurred significantly earlier than control participants'
CRs at the longer ISI. Amnesic patients also produced significantly more
nonadaptive CRs than did control participants, their level of acquisition was
less than that of control participants after equating for ISI, and they did not
show extinction with the longer ISI. These data suggest a role of the hippocampal
system in controlling the precise timing of conditioned eyeblink responses and in
acquiring and extinguishing responses within the context of a temporal
discrimination task.
PMID- 10197903
TI - Hippocampectomized rats are capable of homing by path integration.
AB - Navigation in rodents is mediated by at least 3 mechanisms: guidance, path
integration, and landmark learning. The hippocampus is necessary for spatial
learning based on distal landmarks, and it has been suggested that the
hippocampal formation performs a form of path integration in updating place cell
firing; however, the necessity of the hippocampus for path integration has not
been clearly established. Rats with extensive neurotoxin lesions of the
hippocampus and control rats were trained on 2 tasks in which they were required
to move in total darkness from one location to another and then return to the
start point. Hippocampal and control rats both used path integration in solving
these tasks and did not differ in terms of the distributions of their arrival
points on the return paths. We conclude that neuronal circuits sufficient for
computing a homing vector using path integration are located outside the
hippocampus.
PMID- 10197904
TI - Involvement of rodent prefrontal cortex subregions in strategy switching.
AB - The present study examined whether inactivation of the prelimbic-infralimbic
areas or the dorsal anterior cingulate area impairs strategy switching in the
cheeseboard task. After implantation of a cannula aimed at either the prelimbic
infralimbic or dorsal anterior cingulate areas, all rats were tested in a spatial
and a visual-cued version of the task. Some of the rats received the spatial
version first, followed by the visual-cued version. The procedure for the other
rats was reversed. Infusions of 2% tetracaine into the prelimbic-infralimbic or
dorsal anterior cingulate areas did not impair acquisition of the spatial or
visual-cued versions. However, inactivation of the prelimbic-infralimbic areas,
but not the dorsal anterior cingulate area, impaired learning when rats were
switched from one version to the other. These findings suggest that the prelimbic
infralimbic areas are involved in switching to new behavior-guiding strategies.
PMID- 10197905
TI - Impaired allocentric spatial working memory and intact retrograde memory after
thalamic damage caused by thiamine deficiency in rats.
AB - Rats were tested on an allocentric-spatial working-memory task--delayed matching
to-place (DMTP) in a water maze--before and after either pyrithiamine-induced
thiamine deficiency (PTD) or electrolytic lesions of the lateral internal
medullary laminae (IML), an area damaged by PTD. DMTP trials consisted of paired
swims, with the escape platform in a new location on each trial. PTD rats were
impaired at retention delays of 300 s, but not at delays of 4 or 60 s. Rats with
IML lesions performed normally at all delays. Both groups displayed normal
retention of object-discrimination problems that they had learned at different
intervals before treatment (5 weeks, 3 weeks, and 1 week). The results suggest
that PTD causes delay-dependent deficits of allocentric spatial working memory
and that damage outside the IML is probably responsible. Neither PTD-induced
diencephalic damage nor restricted IML lesions appear to produce a global
retrograde amnesia.
PMID- 10197906
TI - Behavioral mechanisms for active maternal potentiation of isolation calling in
rat pups.
AB - The ultrasonic vocalization (USV) response of the isolated infant rat is a
promising model for studying the neurobiology of an early anxiety state, and
potentiation of the USV response after brief maternal encounters is a newly
discovered behavioral regulator of this state. Using experimental variations in
the contexts and patterns of maternal behavior during pup encounters and manual
simulations of maternal behavior, we have identified several specific mother-pup
interactions that cause potentiation. When one of these, pup carrying, was
manually simulated, potentiation followed only if a characteristic postural
transport response had been fully expressed by the pup. These behavioral
mechanisms and other data suggest hypotheses for the development and adaptive
role of maternal potentiation.
PMID- 10197907
TI - Impairment of cingulothalamic learning-related neuronal coding in rabbits exposed
to cocaine in utero: general and sex-specific effects.
AB - Neuronal activity was recorded in the cingulate cortex and the limbic thalamus in
Dutch-belted rabbits (Oryctolagus cuniculus) exposed to cocaine (8 mg/kg/day
i.v.) or saline in utero during acquisition and reversal learning of a
discriminative avoidance response. Anterior cingulate cortical excitatory
training-induced activity (TIA) was attenuated in cocaine-exposed female rabbits
during acquisition and reversal learning, but only during reversal learning in
male rabbits. Posterior cingulate cortical excitatory TIA was lessened in cocaine
exposed rabbits during acquisition, whereas discrimination between the positive
and negative cues was enhanced. Neuronal firing was attenuated in the anterior
ventral thalamus in cocaine-exposed rabbits during acquisition and reversal
learning. Behavioral learning was normal in cocaine-exposed rabbits. Other data
suggest that rabbits exposed to cocaine in utero exhibit a learning deficit when
trained with nonsalient cues.
PMID- 10197908
TI - Effects of lesions to the cerebellar vermis and hemispheres on timing and
counting in rats.
AB - The effects of lesions to the cerebellum on numerical and temporal discrimination
were examined in rats using a psychophysical choice procedure. Lesions to the
cerebellar hemispheres but not the cerebellar vermis produced performance
deficits in a numerical discrimination task (2-8 events) and a milliseconds
temporal discrimination task (0.2-0.8 s). However, temporal discriminations in
the seconds range (2-8 s) were unaffected by either type of lesion. Using W. H.
Meck and R. M. Church's (1983) mode-control model of timing and counting, these
findings suggest that damage to the cerebellar hemispheres influences a source of
constant variability (e.g., switch processes) because constant variability is a
prominent source of error during both milliseconds timing and counting but is
masked by other sources of variability when timing longer durations (>2 s).
PMID- 10197909
TI - Strain distribution of mice in discriminated Y-maze avoidance learning: genetic
and procedural differences.
AB - The current study was conducted to characterize discriminated avoidance learning
in mice by using a Y-maze task. In Experiment 1, the task parameters were
manipulated, including the amount of time spent in the start arm, the amount of
time to make the avoidance response, and the intertrial interval (ITI) using C57
x SJL F1 hybrid mice. Avoidance performance was significantly improved with
longer times to avoid the shock and longer ITIs. In Experiment 2, mice from 4
inbred strains (BALB/cByJ, DBA/2J, C57BL/6J, and SJL/J), an F1 hybrid (C57 x
SJL), and 1 outbred strain (CD1) were tested with various ITIs. Strain
differences were observed in avoidance learning, with BALB, DBA, C57 x SJL and
CD1 mice showing significantly better avoidance learning than C57 mice, which
were better than SJL mice. These data demonstrate that Y-maze performance is
significantly influenced by the genetic background of the mouse and the
parameters of the task.
PMID- 10197910
TI - Interactive contributions of intracellular calcium and protein phosphatases to
massed-trials learning deficits in Hermissenda.
AB - Using Hermissenda as subjects, massed-trials training deficits were examined.
Associative pairings of light and rotation induced a progressively greater
conditioned foot contraction in response to light as the intertrial interval
(ITI) was extended (up to 8 min). In contrast, a short ITI (30 s) produced no
evidence of learning. In a corresponding in vitro conditioning experiment that
mimicked training of the intact animal, facilitation of neuronal excitability in
the animal's B photoreceptors paralleled the results obtained in vivo. Imaging of
intracellular Ca2+ using Fura-2 indicated that Ca2+ levels remained elevated
during short ITIs. This Ca2+ accumulation appears to induce activation of protein
phosphatases because normal facilitation of the B photoreceptors was induced with
a short ITI if training occurred in the presence of a phosphatase inhibitor.
These results suggest that intracellular Ca2+ and protein phosphatases contribute
interactively to the kinetics of memory formation and provide evidence that an
accumulation of intracellular Ca2+ across training trials may impede memory
formation.
PMID- 10197911
TI - Functional interaction between entorhinal cortex and basolateral amygdala during
trace conditioning of odor aversion in the rat.
AB - In rats, conditioned odor aversion (COA) occurs only if the time interval
separating the odor from the subsequent intoxication is very short suggesting
that the memory trace of the odor is subject to rapid decay. Recent results from
our laboratory have found that lesion of the entorhinal cortex (EC), and
activation of the basolateral nucleus of the amygdala (BLA) rendered COA tolerant
to long interstimulus interval. The present study examined whether the odor
memory trace depends on the interaction between the EC and the BLA. Rats lesioned
in the EC received infusions of muscimol (a GABA(A) receptor agonist) into the
BLA immediately after the odor presentation during acquisition of COA. Injection
of muscimol into BLA prevented tolerance of COA to long interstimulus interval
induced by EC lesions. This suggests that EC modulates the short-term memory
trace of the odor by controlling the GABAergic activity of the BLA during
acquisition of COA.
PMID- 10197912
TI - Learning to cope with biting flies: rapid NMDA-mediated acquisition of
conditioned analgesia.
AB - A 30-min exposure to intact biting flies (stable flies) induced an opioid
mediated analgesia in fly-naive male deer mice, whereas exposure to either
altered biting flies whose biting mouthparts were removed or nonbiting house
flies had no significant effects. However, mice that were previously exposed to
intact stable flies for 30 min exhibited significant analgesia when exposed 24
168 hr later to stable flies whose biting parts were removed, but not to
nonbiting house flies. Administration of the specific N-methyl-D-aspartate (NMDA)
antagonist NPC 12626 to fly-naive mice before exposure to intact flies, although
not significantly reducing the analgesic response, blocked the subsequent
conditioned analgesia. Naloxone, which blocked the intact biting fly-induced
analgesia, did not alter the acquisition of the conditioned analgesic response to
the altered stable flies. This demonstrates an NMDA-mediated acquisition of
conditioned analgesia to a natural aversive stimulus.
PMID- 10197913
TI - Postacquisition scopolamine treatments reveal the time course for the formation
of lamb odor recognition memory in parturient ewes.
AB - Institut National de Recherche Agronomique/Centre National de la Recherche
Scientifique Within 4 hr after parturition, ewes learn to recognize the odor of
their lamb. Whether scopolamine, a muscarinic antagonist, interferes with lamb
odor retention was studied. After 4 hr of mother-young contact, ewes were
separated from their lambs for 3 hr. During separation, they received
intramuscular injections of saline, methylscopolamine (peripheral muscarinic
antagonist), or scopolamine. Only scopolamine (100 microg/kg) prevented
subsequent lamb recognition. To assess whether this effect depended on the
duration of the learning phase, mothers remained with their lambs for 4, 8, or 16
hr before the 3-hr separation period and the scopolamine treatments. Ewes treated
after 4 or 8 hr of contact displayed disturbed lamb recognition, whereas those
having 16 hr of contact did not. Activation of central muscarinic receptors is
therefore important for the formation of lamb odor recognition memory during a
critical period of less than 16 hr postpartum.
PMID- 10197914
TI - Disconnection of the amygdala central nucleus and substantia innominata/nucleus
basalis disrupts increments in conditioned stimulus processing in rats.
AB - Rats with a neurotoxic lesion of the amygdala central nucleus (CN) in one
hemisphere and a 192 immunoglobulin G (192IgG)-saporin lesion of cholinergic
neurons in the contralateral substantia innominata/nucleus basalis (SI/nBM)
failed to show the enhanced attentional processing of a conditioned stimulus (CS)
observed in sham-operated rats when that CS's predictive value was altered.
Performance of these asymmetrically lesioned rats was poorer than that of rats
with a unilateral lesion of either structure or with a symmetrical lesion of both
structures in the same hemisphere. These results implicate connections between
the CN and SI/nBM in the incremental attentional processing of CSs, extending
previous research that has shown similar effects of bilateral lesions of either
the CN or the SI/nBM.
PMID- 10197915
TI - The dopaminergic modulation of fear: quinpirole impairs the recall of emotional
memories in rats.
AB - Past studies examining the contributions of dopamine to fear have produced
inconsistent results. The present experiments reevaluated this issue. It was
found that systemic pretreatment with the D2 agonist quinpirole before pairing 2
conditioned stimuli (CSs; CS2-CS1) dose dependently blocked the acquisition of
second-order fear conditioning. Quinpirole's actions were not due to nonspecific
impairments in the ability to perceive the CSs, or form and store an association,
because the identical drug pretreatment before pairing the same 2 CSs had no
effect on the acquisition of sensory preconditioning. In a separate study, rats
were given fear conditioning while untreated and then received extinction
sessions while under the influence of quinpirole or its vehicle. Quinpirole
pretreatment blocked extinction. Findings suggest that quinpirole decreased fear
by blocking the retrieval of a learned association between a CS and unconditioned
stimulus (US), rather than by devaluing the US, which would have resulted from
summation of quinpirole's appetitive properties with the aversive properties of
fear.
PMID- 10197916
TI - Cortisol facilitates induction of sexual behavior in the female musk shrew
(Suncus murinus).
AB - The role of cortisol in sexual behavior in the female musk shrew (Suncus murinus)
was examined. High levels of cortisol were associated with sexual receptivity, as
indicated by species-typical tail-wagging behavior, during brief (15-min) mating
tests. When cortisol production was blocked by metyrapone, an 11-beta-hydroxylase
inhibitor, females exhibited reduced sexual behavior relative to controls, an
effect that was reversed with acute cortisol replacement. These results indicate
that cortisol facilitates, rather than inhibits, sexual behavior in this species
and expands the comparative understanding of hypothalamic-pituitary-adrenal (HPA)
effects on reproduction.
PMID- 10197917
TI - Lactation-induced reduction in rats' acoustic startle is associated with changes
in noradrenergic neurotransmission.
AB - The acoustic startle response (ASR) with or without fear conditioning was
compared between cycling (CYC) and lactating (LACT) female rats. ASR sensitivity
to changes in endogenous noradrenergic (NA) release was examined using the alpha
2 NA receptor drugs yohimbine and clonidine. Groups of CYC and LACT females were
also tested in the open field. ASR was reduced in all LACT, compared with that in
CYC females. Both groups exhibited a robust response to fear conditioning and
unpotentiated ASR subsequent to conditioning was increased in LACT females. The
lowest dose of yohimbine significantly increased ASR in LACT females, but not in
CYC females. Clonidine reduced ASR in both groups of females, with a greater
potency in CYC females. In the open field, LACT females displayed a shorter
latency to emerge, less freezing behavior, and more entries into the field than
did CYC females. The authors concluded that (a) LACT females are less anxious in
a novel environment and that decreased anxiety can be efficiently counteracted by
fear conditioning, and (b) changes in NA neurotransmission contribute to
lactation-induced modifications in ASR.
PMID- 10197918
TI - Chorda tympani nerve transection, but not amiloride, increases the KCl taste
detection threshold in rats.
AB - Water-restricted rats were trained to press one lever after KCl presentation and
the other lever after distilled water. Water reinforcement was given after each
correct response, and a time-out followed each incorrect response. Rats were
trained and tested on KCl stimuli of varying concentrations. Threshold was
defined as the KCl concentration corresponding to 1/2 the maximum asymptote of
performance for each rat. The geometric mean KCl detection threshold for all rats
was 0.033 M KCl. Rats that had the chorda tympani nerve (CT) bilaterally
transected showed an average increase in KCl threshold of approximately 0.60
log10 units, whereas sham-operated rats showed no change. Control rats retested
with 100 microM amiloride added to all KCl concentrations and water displayed no
change in threshold. These results suggest that although the CT contributes
significantly to the rat's sensitivity to KCl, amiloride-sensitive taste
transduction pathways do not.
PMID- 10197919
TI - Effects of glycine or (+/-)-3-amino-1-hydroxy-2-pyrrolidone microinjections along
the rostrocaudal axis of the dorsal periaqueductal gray matter on rats'
performance in the elevated plus-maze task.
AB - The effects of glycine (GLY) or (+/-)-3-amino-1-hydroxy-2-pyrrolidone (HA966), a
GLY receptor antagonist, microinjections into sites along the rostrocaudal axis
of the dorsal periaqueductal gray matter (dPAG) were studied in rats placed on
the elevated plus maze (EPM). Selective alterations in the open-arm entries
(OAEs) or open-arm time (OAT) of the EPM were the indexes of anxiety. HA966 (30
or 100 nmol, 0.3 microl) increased OAEs and OAT in all 3 dPAG sites, suggesting
an anxiolytic effect. GLY (80 and 120 nmol, 0.3 microl) selectively reduced OAEs
and OAT, suggesting an anxiogenic effect only when injections were given within
the caudal dPAG. When administered together, HA966 reversed the anxiogenic effect
of 120 nmol GLY, indicating pharmacological selectivity for the effects of GLY on
GLY receptors. Results reinforce an involvement of N-Methyl-D-aspartate-coupled
GLY receptors in anxiety and suggest that saturation of this receptor may vary
along the dPAG.
PMID- 10197920
TI - Bilateral lesions of the interpositus nucleus completely prevent eyeblink
conditioning in Purkinje cell-degeneration mutant mice.
AB - The authors have previously demonstrated that Purkinje cell-degeneration (pcd)
mutant mice are impaired in eyeblink conditioning (L. Chen et al., 1996a). The
present study addresses the following 3 questions: (a) whether pcd mice perceive
the conditioned and unconditioned stimuli as well as the wild-type mice, (b)
whether pcd mice have a normal sensitization level, and (c) whether the residual
learning in pcd mice is cerebellum-dependent. Results indicated that the pcd mice
exhibited normal tone-induced responses in the cochlear nucleus and normal
sensitivity to heat-induced pain. They showed a similar level of sensitization as
the wild-type mice and were completely unable to learn conditioned eyeblinks
after bilateral lesions aimed at the anterior interpositus nucleus. Thus, pcd
mice are partially impaired in eyeblink conditioning because of a deficiency in
learning mechanisms, and the residual learning in the pcd mice is mediated by the
cerebellar nuclei.
PMID- 10197921
TI - Sustained attachment to the nipple in the newborn rat depends on experience with
the nipple, milk, and the expression of oral grasping.
AB - Newborn rats showed mouthing, licking, and oral grasping when presented with a
surrogate nipple. These responses changed after the pup expressed an oral grasp
response and experienced milk at the nipple. Newborn pups that ingested milk from
the surrogate nipple showed brief oral grasp responses and, when tested 1 hr
later, showed sustained attachment to an empty surrogate nipple. Contact with the
nipple, oral grasping of the nipple, and experience with milk altered subsequent
behavioral responses to the nipple. Classical and instrumental conditioning may
play a role in transforming brief oral grasp responses into longer oral grasp
responses and sustained attachment to the nipple.
PMID- 10197922
TI - Intrahippocampal infusions of a metabotropic glutamate receptor antagonist block
the memory of context-specific but not tone-specific conditioned fear.
AB - The role of metabotropic glutamate receptors (mGluRs) in the acquisition of
learning and memory using fear conditioning as a behavioral model was examined.
The mGluR antagonist (R, S)-alpha-methyl-4-carboxyphenylglycine (MCPG) was
infused into the hippocampus 30 min before fear conditioning, and freezing was
measured during both acquisition and retention tests. The results show that
pretraining antagonism of MCPG-sensitive mGluRs in the hippocampus impaired
context-specific memory for an aversive event during testing. The memory for tone
specific fear, however, remained intact despite pretraining infusion of MCPG.
Treating rats with MCPG did not affect context- or tone-specific fear during
acquisition. Results suggest that mGluR activation may play an important role in
hippocampally mediated memory consolidation.
PMID- 10197923
TI - Cancer nursing: a leading force for health care.
PMID- 10197924
TI - Reducing HIV/AIDS for nursing personnel.
PMID- 10197925
TI - Are you protecting yourself?
PMID- 10197926
TI - Myocardial infarction patients' use of metaphors to share meaning and communicate
underlying frames of experience.
AB - The onset of a myocardial infarction (MI) is frequently associated with distinct
sensations that may shape the personal meaning of the MI illness experience.
Although highly important, patients may have difficulty communicating the
personal meaning of the MI illness experience because of lack of congruence
between the clinician's and patient's frames of experience. The frame of
experience defines the context and agenda for encounters from each participant's
perspective. This secondary analysis of data explored MI patients' use of
metaphorical language to convey aspects of their underlying frame of experience.
Specifically, this paper addressed (a) the structural and linguistic features of
metaphorical language used by patients to describe MI pain, (b) the content and
structure of associated patient metaphors, and (c) the similarities and
differences between the content of patient metaphors and descriptions of MI pain.
Our findings confirm that even in encounters characterized by clinician
imposition of an organizing framework upon the patient encounter, patients use
metaphors to reveal their underlying frame of experience and aspects of the
personal meaning of the MI illness experience. Furthermore, although non
metaphorical descriptions provide insights into the patients' cognitive
understanding of events associated with the MI, metaphorical descriptions are
particularly helpful in eliciting aspects of the affective response to the MI.
PMID- 10197927
TI - Listening to them and reading me: a hermeneutic approach to understanding the
experience of illness.
AB - Developing a method that is pragmatic yet theoretically consistent with the
philosophies of hermeneutics and phenomenology is a constant hurdle for any
researcher endeavouring to engage their inquiry in this manner, particularly when
its proponents refute the credence of hermeneutics as a research method. This
paper discusses how Van Manen's six research activities can act as a framework,
that when modified to suit the particular needs of the research project, can
promote a process of inquiry that works with these philosophies towards an
unfoldment of new understandings of the human experience in illness.
PMID- 10197928
TI - Conceptualization and measurement of quality of life as an outcome variable for
health care intervention and research.
AB - If health care providers are to be able to document effective outcomes resulting
from their interventions, they must first develop clear conceptual definitions
for the outcomes, and then select measures that represent these concepts. No
consensus exists in the health care disciplines about what quality of life is or
how it should be measured. This paper presents historical and conceptual
arguments in favour of a particular definition of quality of life, and
distinguishes between quality of life and concepts often confused with it in the
literature: symptoms, mood, functional status, and general health status. Whether
quality of life is actually amenable to change as a result of health care
interventions, and whether we ought to be trying to influence clients' quality of
life is also discussed. We conclude that quality of life is an important outcome
of health care intervention. However, traditional approaches to influencing
quality of life may be misdirected, and the relative importance of our
interventions to clients--whose opinions matter the most--ought to be put into
perspective.
PMID- 10197929
TI - Measuring patient satisfaction with nursing care: experience of using the
Newcastle Satisfaction with Nursing Scale.
AB - Patient satisfaction with care has frequently been used as a measurement of
quality, especially in attempts to demonstrate the benefits of changes in nursing
practice. Unfortunately such attempts have frequently failed as patient
satisfaction ratings have lacked sensitivity, consistently achieving very high
scores. They have also failed to isolate the nursing component from the whole
health care experience. The Newcastle Satisfaction with Nursing Scale (NSNS) has
been developed after extensive research work as an attempt to establish reliable
and valid measures of patients' experiences of and satisfaction with nursing
care. This study evaluated the use of the NSNS in practice and found that it was
readily understood by patients and easily administered by clinical staff.
However, several lessons were learnt which could help its administration. The
results demonstrated a very high degree of satisfaction with nursing care which
left the discriminatory ability of the scale open to question, although its
potential benefits in standard setting were demonstrated. Further evaluative
studies are needed if the potential benefits of the NSNS are to be fully
realised.
PMID- 10197930
TI - Translation of questionnaires and issues of equivalence.
AB - The validity of studies using translated instruments may be questioned when there
is a lack of attention to and/or minimal explanation of the procedures used for
determining the equivalence between the primary and secondary language tool.
Ensuring equivalence of a translated Chinese version of the Menstrual Distress
Questionnaire is an important prerequisite for identifying culturally specific
expressions of concepts under investigation and for cross-cultural comparisons.
This paper examines the principles and procedures for determining equivalence of
translated tools and their application to the development of an equivalent
Chinese version of the Menstrual Distress Questionnaire. Translation and back
translation were used to develop a Chinese version of the Menstrual Distress
Questionnaire. Bilingual university students completed both versions of the
Menstrual Distress Questionnaire. Most of the Menstrual Distress Questionnaire
items had an acceptable Kappa of >0.4. Intraclass correlation coefficients
indicated moderate to high levels of equivalence for total scores and all scales.
Improvement in the translation of some items is needed to further enhance the
equivalence of the Chinese version of the Menstrual Distress Questionnaire.
PMID- 10197931
TI - Analysing qualitative data: computerized and other approaches.
AB - Analysis of qualitative data can be done 'manually' using a variety of techniques
such as 'cut and paste' and use of coloured pens to categorize data and develop
theoretical explanations. More recently a number of computer software packages
have been developed to mechanize this 'coding' process as well as to search and
retrieve data. This article reviews the background to and advantages and
disadvantages of computerized approaches, and compares these with manual
techniques used in a number of recent nursing PhD studies. It is concluded that
beginning researchers conducting small-scale studies would be best recommended to
use a manual approach in order to gain insight into the intuitive aspects of
analysis which are the essential basis of any method of analysis, including
computerized forms.
PMID- 10197932
TI - The language of mental health nursing reports: firing paper bullets?
AB - A great deal of the caring work of nursing is accomplished and mediated through
language. This paper attempts to characterize some of this language in
quantitative and stylistic terms in an attempt to characterize the genre of
nursing report language. Nursing students (n = 26) and graduate nurses (n = 3)
viewed a videotape of a person being interviewed by a psychiatrist and produced
written reports. These showed a large proportion of words relating to the person
and to feelings and needs, compared to existing databases of the English language
in general. The language produced by the participants also contained many modal
or modifying words and is similar to spoken rather than written English in terms
of the proportion of lexical content. There was much diversity in their
descriptions and the vocabulary used to refer to the client. Graduate nurses
showed more scepticism of the evidence provided by the video and advocated more
investigation and questioning of the client. The use of standard forms and
techniques of expression suggests that these reports were assembled on a language
production line. Finally, we advocate a more systematic approach to educating
nursing students about the power of the language they use.
PMID- 10197933
TI - Named nursing: in whose best interest?
AB - This paper explores certain influences and issues surrounding the implementation
and application of the named nurse concept. The author critically examines the
proposals that primary nursing increases job satisfaction, cost effectiveness and
quality of care, and suggests that as primary nursing appears to be the template
for named nursing, these are factors which may have influenced the former British
government's decision to implement the concept of named nursing. Owing to
problems regarding the reliability and validity of much of the research, the
author draws the conclusion that the direct extrapolation from one concept (such
as primary nursing) to another (such as named nursing) is perhaps open to
question. The author also analyses other issues related to the implementation and
use of the named nurse concept including advocacy and accountability, and
proposes that the introduction of individualized care, and in particular named
nursing, perhaps serves the drive towards the professionalization of nursing
first, and the patient second, and if so questions whether there is a need to
reconsider the aim of nursing.
PMID- 10197934
TI - Nurse prescribing: radicalism or tokenism?
AB - The creation of The Medical Products (Prescription by Nurses, etc.) Act 1992 has
been generally welcomed by the nursing profession. This article seeks to
introduce a note of scepticism about the assumed motivations for its introduction
through an analysis of various legal, ethical, economic and political dimensions.
In reviewing the position of nursing vis-a-vis medicine it is argued that one of
the ways that nursing has sought to improve its professional position is to take
on work previously done by doctors, and nurse prescribing can be seen in the
context of the concurrent de-regulation of medicines, allowing greater access to
medicines and therefore greater consumer choice. This de-regulation stems from
the liberation ideology of the previous Conservative government. Viewed in this
way nurse prescribing, particularly with reference to the limited nature of the
nursing formulary, can be seen to be anomalous. In the light of this analysis,
the reasons generally put forward (notably in the Crown Report 1989) for the
introduction of nurse prescribing could be seen to be peripheral to its real
purpose. It is argued that the most convincing reasons for its introduction
relate to the medical profession as a social institution. It is proposed that the
three primary aims behind the introduction of nurse prescribing are: the saving
of money; the transfer of routine medical work to nursing; and a challenge to the
professional monolith of medicine.
PMID- 10197935
TI - Continuing education in nursing: a review of the literature.
AB - The literature concerning continuing professional education (CPE) in nursing will
be reviewed, with an emphasis on the experience of CPE in the United Kingdom
(UK). The reviewed literature will cover aspects of the implementation of CPE,
including motivational factors, needs analysis and outcome evaluations, and in
addition CPE in the UK will be set in its socio-political context. The literature
shows a fragmented, inequitable and poorly funded provision of CPE to date in the
UK. The literature has not shown the cyclical nature of CPE, suggesting that a
more holistic approach to educational research is needed. There continues to be a
lack of research showing the impact of CPE on patient care. If this is not
remedied it may be difficult to justify future expenditure of public funds on CPE
for nurses.
PMID- 10197936
TI - The concepts of expectation and satisfaction: do they capture the way patients
evaluate their care?
AB - The measurement of patient satisfaction has become a common way to elicit
patients' views of their health care. However, difficulties arising from the
limited theoretical underpinning of satisfaction, the difficulty in defining
expectations and satisfaction and the methodological problems associated with
their measurement have cast doubt on the validity of studies. This paper reviews
the methodological and theoretical difficulties in measuring these concepts and
argues that a better understanding of expectations and satisfaction, which is
based in patient experience, must first be achieved before theoretical modelling
and valid measurement can progress. It presents the findings of a study which
attempted to clarify the concepts of expectations and satisfaction by exploring
the experience of cardiac patients. The findings are discussed in the context of
the key issues in this area.
PMID- 10197937
TI - Warrantable evidence in nursing science.
AB - Consensus among nurse scholars has not been reached regarding suitable qualities
for accepting or rejecting the evidence arising from various world views. The
authors' purpose in writing the paper is to describe the qualities or warrants
for evaluating scientific findings (the 'evidence') of different research
perspectives. The warrantable evidence pertinent to post-positivist,
interpretivist, critical social theorist, and feminist perspectives are described
and common warrants are suggested. Three warrants common to these scientific
perspectives are proposed: (a) scrutiny and critique of methodological rigor and
findings by the scientific community; (b) corroboration and intersubjectivity;
and (c) scope of the evidence. The identification of common warrantable evidence
will assist nurses in developing some core values regarding the constituents of
good science or good scholarship even in the face of pluralism in nursing science
approaches.
PMID- 10197938
TI - Guide to practice or 'load of rubbish'? The influence of care plans on nursing
practice in five clinical areas in Northern Ireland.
AB - A nursing care plan is a written, structured plan of action for patient care.
There is strong evidence that care plans are viewed negatively by nurses and
poorly implemented, with little evidence to suggest that they have any positive
effect on quality of care or patient outcomes. The project reported in this paper
aimed to investigate how nursing care plans were being used in five clinical
areas, and to assess their influence on nursing practice. An exploratory,
predominantly qualitative research design was selected utilizing participant
observation, focus groups and diaries. In four of the five clinical areas, the
'activities of daily living' section of care plans had no apparent positive
influence on nursing practice which was driven by other factors and sources of
information. Care plans in the remaining ward were clinically led and locally
owned, and in this setting they operated as an important guide to practice. It is
concluded that a reinvention of the nursing care plan is needed without the
constraint of a nursing model as its necessary foundation. New and imaginative
plans of action for patient care should be encouraged, developed at ward level
and tailored to the demands of the clinical area. These should contain a minimum
of documentation and integrate with nursing practice.
PMID- 10197939
TI - Strategies for coping with labour: does antenatal education translate into
practice?
AB - There is little evidence to associate attendance at antenatal classes with a
reduction in psychological distress or increased satisfaction with the experience
of labour. There may be several reasons for this, including failure to implement
coping strategies. A within-subjects research design explored the use in labour
of coping strategies taught in antenatal classes and the role of practice.
Women's views about using these strategies and their expectations of their
midwives and birth companions were also identified. Following Ethics Committee
approval and providing informed consent, 121 nulliparous women completed a
questionnaire at their final antenatal class. This included questions on
confidence and the amount of effort required to use coping strategies, the
involvement hoped for from birth companions and midwives in using coping
strategies in labour and satisfaction with the amount of practice of coping
strategies. Within 72 hours of delivery, women were interviewed to obtain a
narrative of the events of labour and their use of the coping strategies (sighing
out-slowly breathing, Laura Mitchell relaxation and postural change). A
questionnaire obtained information on the involvement of the midwife and birth
companion. Women used the three coping strategies to different extents. Midwives
were not involved to the extent that women had hoped for antenatally. Birth
companions achieved a level of involvement closer to women's hopes than that
achieved by midwives. A significant proportion of women expressed dissatisfaction
with the amount of practice of coping strategies during antenatal classes. The
findings of this study of a group of well-prepared women raise questions about
the correct components of antenatal classes and how midwives and birth companions
can be involved optimally in this aspect of a woman's labour. Further research is
required to determine how women can best be helped to cope with the experience of
labour.
PMID- 10197940
TI - Social support and antenatal clinic attendance among Thai pregnant women in
Hatyai, a city in southern Thailand.
AB - Many studies in western countries have shown that persons who have a high level
of social support are likely to have better health behaviours, including use of
preventive health services, than those who have low support. The present study
aims to investigate the impact of level of social support among Thai pregnant
women on their attendance at antenatal care (ANC) clinics. The study was
conducted in Hatyai, a city in Southern Thailand, between 1990 and 1991.
Relationships between various measures of the women's social support and their
use of antenatal clinics were assessed. Open ended and closed ended questions
were used to gather information relating to these women's level of social
support, including the number of supporters and their age, the percentage of
females among the supporters, the sources of support (spouse, kin, friend and
health professionals), the frequency of contact, the types of support and the
sufficiency of support. Social support indices were constructed: sources of
support indices, a social network index, a subjective support index, and a social
support index. One hundred and seventy-seven postpartum women were interviewed at
their homes. Spouses, relatives and friends were important sources of the four
principle types of support, namely emotional, instrumental, information and
appraisal supports. Less than 10% of the women studied identified health
personnel as providing support. The majority of supporters were women who had
daily, face-to-face communication with the women studied. Approximately 76% of
the women studied had sufficient support. The majority of supporters, except
health personnel, provided all four types of support. Only 47% of the women
studied made four or more antenatal clinic visits as recommended by the Thai
government. No significant relationship between the indices of social support and
the use of ANC clinics was identified. The Thai extended family by its nature
generates large numbers of supporters. Little variation in support levels among
all the women therefore occurred. Support to the women could have positive and/or
negative effects on the women's use of ANC clinics. It was concluded that in Thai
communities, social support is not an important determinant of the use of ANC
clinics and the indices of social support were not the most appropriate
techniques to use in the communities.
PMID- 10197941
TI - Relationships between family dynamics of Finnish child-rearing families, factors
causing strain and received support.
AB - The aim of this study was to determine the relationships between family dynamics,
the factors causing strain on child-rearing parents and the support available to
families from public health nurses. Family dynamics was defined as the family's
unique way of functioning and was conceptualized by means of six different
dimensions. Questionnaires were sent to 118 families, and of these 85 mothers and
79 fathers participated in the study. According to the findings the majority of
parents involved in bringing up children aged 3-4 years assessed their families
to be well-functioning. There was a correlation between a low level of factors
causing strain on the family and a positive evaluation of family dynamics based
on the various dimensions. According to the mothers the support, i.e. emotional,
appraisal and instrumental support, received from public health nurses, along
with a small number of strain-causing factors on the partner relationship,
correlated well with their positive assessments of the mutuality and flexibility
of their families.
PMID- 10197942
TI - Abused women and child custody: the ongoing exposure to abusive ex-partners.
AB - Abuse of women in domestic relationships has become an epidemic. Research studies
have documented that abuse does not end when a woman with children leaves the
abuser but, in fact, the danger increases. A father's legal right to custody of
and access to his children and the children's bond with their father prevent a
woman from truly breaking free of her abuser. Theoretical literature has
addressed how custody and access can serve as a means for an abuser to continue
his abuse and expose his children to ongoing abuse and discord. Research on how
custody and access issues are affecting abused women is limited. Key details
about this phenomenon are not known. Hence, a research study using the
qualitative methodology of phenomenology was conducted on abused women's
experiences with custody and access and the ongoing exposure to abusive ex
partners. Six single mothers who had left abusive relationships and were at the
time sharing custody of and/or access to their children with their abusive ex
partners participated in the study. Unstructured, non-directive interviews were
conducted. Direction for analysis was taken from the specific steps outlined by
Giorgi. Data analysis revealed that all of the women were living in great fear
for their safety and that of their children. The ongoing danger and stress of
living with the restrictions of the law took its toll on the women and ultimately
affected their physical health and psychological well-being. The women described
their experiences as having four components: (1) safety--living with ongoing
danger; (2) stress--living with the restrictions of the law and the legal system;
(3) coping--social support systems; and (4) to heal and move forward in life.
PMID- 10197943
TI - The impact of knowing your child is critically ill: a qualitative study of
mothers' experiences.
AB - Discussion in this paper is drawn from an exploratory study designed to elicit
mothers' lived experiences of crisis and coping, and their experiences of nursing
following the unexpected emergency admission of their child to the paediatric
intensive care unit (PICU). An in-depth critique of literature supporting this
study has been published. Two theoretical perspectives serve as a basis for this
exploratory study: firstly, the idea that in a crisis situation, a mother's
ability to cope and function is influenced by therapeutic interventions of nurses
by meeting her needs in a holistic way; and secondly, symbolic interactionism,
that focuses on the meaning of events to mothers. Data were elicited through
focused interviews with 10 mothers of children aged between 3 months and 15 years
who had been admitted unexpectedly to the PICU with a life threatening condition.
Findings reveal the major impact of crisis on mothers immediately following their
child's critical illness and admission to PICU, and this specific aspect
therefore warrants in-depth discussion and analysis. The study did not generate a
theory; however, important recommendations are made for nursing practice and
research in relation to the impact of crisis experienced by mothers. Nursing
practice issues include meeting the psychosocial needs of parents prior to and
immediately after admission, and the importance of family-centred nursing care.
Issues for nursing research include exploring how families cope with the impact
of crisis and critical illness.
PMID- 10197945
TI - Specialist nurse counsellor interventions at the time of diagnosis of breast
cancer: comparing 'advocacy' with a conventional approach.
AB - Over recent years, specialist breast care nurses have become increasingly
recognized as core members of any breast care team within the UK. Part of the
role is to support patients at the highly stressful stage of receiving a
diagnosis. This paper describes an 'advocacy' style of nurse counsellor
intervention which aims to improve patients' preparation for, and involvement in,
the diagnostic consultation and provides a framework for future counselling
support. One hundred and three women undergoing surgery following diagnosis of
breast cancer or a benign breast lump were supported using either this advocacy
intervention or a more conventional model of care. The aim was to identify the
most effective and appropriate method of intervening at this important stage.
Assessment took place before surgery, with 2-week and 6-month follow-ups, and
included the Hospital Anxiety and Depression Scale, Rotterdam Symptom Check List
and semi-structured interviews addressing perceived quality of care, involvement
in decision-making and psycho-social functioning. Whilst the results of many
measures were similar for women in the two intervention groups, qualitative data
support the implementation of the advocacy method by the breast care nurse.
PMID- 10197944
TI - Daily pain assessment: value for nurses and patients.
AB - Current guidelines for pain management recommend systematic assessment of pain. A
few standardized tools exist for the daily assessment of pain intensity, for
example the numeric rating scale or visual analogue scale, yet these instruments
are rarely used by nurses. In the study reported in this paper, a numeric rating
scale accompanied by an educational programme for nurses, was implemented in
three hospitals. The paper describes the feasibility of daily pain assessment
from the nurses' and patients' perspective in multiple settings. The outcomes
studied were the professional compliance of nurses with daily pain assessment,
and the value of daily pain assessment for both nurses and patients. The results
show that nurses' compliance with daily pain assessment is high (73.9%) and that
daily pain assessment is feasible and valued by nurses; however, differences
between the three hospitals and two specialties (medical vs. surgical wards) were
found. Although patients have difficulty with expressing their pain by use of a
number, almost all patients are able to give a pain score and a majority is
positive about daily pain assessment. From this study it can be concluded that
daily pain assessment is practical and appreciated by nurses as well as patients,
but attuning the implementation protocol to the needs of the specific setting is
necessary.
PMID- 10197946
TI - The community gerontological nurse: themes from a needs analysis.
AB - With the move of care into the community, the role of nurses caring for older
people is changing. However, nurses may not be adequately prepared to cope with
this changing role, especially if their training and experience have been
primarily hospital based. This study involves an educational needs analysis of
registered nurses working in the care of older people in nursing homes and
clients' own homes. It is based on focus groups with registered nurses and
individual interviews with other professionals, as well as group discussions with
older people. The aim of this project is to provide research-based input into the
design of a new community care of older people module, to be offered at Napier
University, Edinburgh from February 1998. The results presented here consist of
three themes or patterns that have emerged from the interview data. The
specialist/generalist theme concerns issues of role definition and gerontological
specialism. The social/medical theme addresses the shift towards a social model
of care when nurses move into the community settings. Finally, the physical
health/mental health theme represents the need for greater integration of skills
and knowledge from both mental health and general health nursing in the field of
community care for older people. The results indicate the need for significant
attitude changes and provide a major challenge to educationalists.
PMID- 10197947
TI - Attitudes of university students towards HIV/AIDS.
AB - The purpose of this study was to assess, in one university in Finland, students'
attitudes and feelings towards HIV/AIDS while they were studying for their first
year at the University of Oulu. This study is part of a larger research project
concerning HIV/AIDS in the Department of Nursing at the University of Oulu. The
results can be used in planning and implementing health education for young
people. The data were collected by using a questionnaire with both structured and
open-ended questions. The study group consisted of 245 students who had started
their studies in the autumn of 1993. The data were analysed by using cross
tabulation (chi-square test) and inductively by content analysis. The most
important source of knowledge concerning HIV/AIDS was television (84%) and 30% of
the students had obtained their knowledge from a school nurse. Even when there
was a lot of knowledge available to the students, they estimated their knowledge
as insufficient and defined HIV more correctly than AIDS. Knowledge did not
increase the use of safe sex but limited sexual behaviour. Religion had an
importance for sexual behaviour. Female students were more sexually active than
male students. The feelings towards HIV/AIDS were more often negative than
positive or neutral and the students felt stronger negative feelings towards AIDS
than HIV. The negative feelings were often based on fear. The differences between
the faculties were minimal.
PMID- 10197948
TI - AIDS in southern Thailand: stories of krengjai and social connections.
AB - HIV-disease in southern Thailand has reached epidemic proportions. The declining
Thai economy, coupled with social discrimination among people with the disease,
has adversely affected individual, family and community krengjai. Among Thai's,
krengjai is used to describe social order, avoid personal conflict, and maintain
harmony in relationships. Using the framework of story, this narrative study
explores the experiences of five individuals with HIV-disease and their tenuous
relationship with krengjai.
PMID- 10197949
TI - Terminally ill patients' and lay-carers' perceptions and experiences of community
based services.
AB - This paper reports on terminally ill patients' and their lay-carers' perceptions
and experiences of community-based services. It forms part of a larger
investigation which examined the extent of service provision and any perceived
gaps and problems from the perspectives of both clients and providers of
community-based assistance for the terminally ill. The participants were nine
terminally ill patients and 12 lay-carers receiving community nursing care.
Fifteen face-to-face, semi-structured interviews were conducted to elicit their
experiences and perceptions of the care being provided. Qualitative, thematic
analysis was carried out on the audio-taped interviews. On the whole, respondents
reported a high level of satisfaction and appreciation for the help provided.
Several areas appeared more problematic, however, and warrant further
consideration. These include perceptions of health professionals, particularly
their role domains, power and expertise, and some of the practical disadvantages
and problems faced by some patients and their families. These are illustrated and
the implications for dying patients, their lay-carers and community-based health
professionals are discussed.
PMID- 10197950
TI - Managing caregiver tasks among family caregivers of cancer patients in Hong Kong.
AB - Twenty-nine family caregivers of terminally ill cancer patients in Hong Kong were
asked about their perceived difficulty in managing caregiver tasks. Results
showed that the level of difficulty in handling the three main aspects of tasks,
that is the direct care, intrapersonal tasks, and interpersonal ties, were
similar (chi2 = 0.71, P > 0.05). The individual tasks identified as extremely
difficult included compensation for personal time (31%), updating knowledge of
reimbursement mechanism (20.7%), and emotionally accepting the likelihood of a
progressive downward course of illness (17.2%). Mann-Whitney tests indicated that
caregivers who had a shorter duration of caregiving experience perceived
significantly greater difficulty in direct care (P < 0.05), intrapersonal tasks
(P < 0.05), and overall tasks (P < 0.05). These findings indicate the need for
the provision of counselling and educational support for these caregivers.
PMID- 10197951
TI - Quality of life in newly diagnosed cancer patients.
AB - The aim of this study was to examine which domains of quality of life are most
strongly affected in patients with newly diagnosed cancer, and to examine if
quality of life was related to gender, age, educational level, cohabitation, time
since diagnosis, treatment or type of cancer in these patients. Ferrans and
Powers Quality of Life Index and the Cancer Rehabilitation Evaluation System,
short form, were completed by 131 newly diagnosed Norwegian adult cancer
patients. The patients had different cancer diagnoses, with breast cancer being
the most common type. None of them were terminally ill, and 80% had been
diagnosed within the last 6 months. The patients turned out to be satisfied with
their lives, especially with the family and marital domains. They were least
satisfied with health, functioning and sex life. Analyses of variance and
multiple regression analysis were conducted to examine the impact on quality of
life of cohabiting, age, gender, educational level, cancer diagnosis, treatment
and time since diagnosis. Those cohabiting had significantly higher quality of
life compared with those living alone. In contrast the younger group (19-39
years) living alone had significantly lower quality of life than the older groups
living alone. Although age was only significantly associated with quality of life
in one sub-scale, the elderly people reported their quality of life to be better
in almost all sub-scales. Time since diagnosis was not associated with quality of
life, while treatment was associated with quality of life as measured by Ferrans
and Powers Quality of Life Index. Gender and educational level were only
associated with one or two domains in quality of life, respectively.
PMID- 10197952
TI - When I grow up I want to be a...? Where undergraduate student nurses want to work
after graduation.
AB - It is assumed that the majority of students undertaking undergraduate nursing
education want to become nurses. Little research, however, has examined the
specific areas in which students intend to pursue their careers after graduation.
This paper reviews the results of the author's research, which clearly indicates
that students have firm preconceived ideas as to the areas in which they wish to
practise in the future. Midwifery, paediatrics, operating theatre and
critical/intensive care are highly favoured, while working with the elderly,
psychiatric nursing and community health nursing are significantly less popular.
The implications of this situation for the nursing profession are considered.
PMID- 10197953
TI - An exploration of the preceptor role: preceptors' perceptions of benefits,
rewards, supports and commitment to the preceptor role.
AB - This Australian study, a replication of Canadian research by Dibert & Goldenberg,
was undertaken to explore the relationship between preceptors' perceptions of
benefits, rewards and support, and their commitment to the preceptor role. A
convenience sample of 134 nurse preceptors involved in an undergraduate nursing
course were invited to complete a four-part questionnaire consisting of the
Preceptor's Perception of Benefits and Rewards Scale, the Preceptor's Perception
of Support Scale, the Commitment to the Preceptor Role Scale, and demographic
details. The results, in the main, parallel those of the original research, with
differences reflecting the distinct nature and the more recent use of
preceptorship in Australia. The results indicate a clear commitment to the
preceptor role and a perception that both material and non-material benefits are
derived from acting in the role. Additionally, support from the institution and
coworkers was considered vital for participation in the role. This not only has
implications for nursing educators, administrators and potential preceptors, but
also for those being preceptored.
PMID- 10197954
TI - Children's health: uniting across boundaries. Conference organized by the Society
of Paediatric Nursing of the Royal College of Nursing of the United Kingdom in
conjunction with the journal Paediatric Nursing, held at Forte Posthouse Hotel
Birmingham City, Birmingham, England, 18-20 September 1998.
PMID- 10197955
TI - Feedback: men in nursing.
PMID- 10197956
TI - Characterization of the binding site of the histamine H3 receptor. 1. Various
approaches to the synthesis of 2-(1H-imidazol-4-yl)cyclopropylamine and
histaminergic activity of (1R,2R)- and (1S,2S)-2-(1H-imidazol-4-yl)
cyclopropylamine.
AB - Various approaches to the synthesis of all four stereoisomers of 2-(1H-imidazol-4
yl)cyclopropylamine (cyclopropylhistamine) are described. The rapid and
convenient synthesis and resolution of trans-cyclopropylhistamine is reported.
The absolute configuration of its enantiomers was determined by single-crystal X
ray crystallographic analysis. The distinct trans-cyclopropylhistamine
enantiomers were tested for their activity and affinity on the histamine H3
receptor. (1S,2S)-Cyclopropylhistamine (VUF 5297) acts as an agonist both on the
rat cortex (pD2 = 7.1; alpha = 0.75) and on guinea pig jejunum (pD2 = 6.6; alpha
= 0.75). Its enantiomer, (1R, 2R)-cyclopropylhistamine (VUF 5296), is about 1
order of magnitude less active. Both enantiomers show weak activity on H1 and H2
receptors. All synthetic attempts to cis-cyclopropylhistamine were unsuccessful.
Nevertheless, the results of this study provide an ideal template for molecular
modeling studies of histamine H3 receptor ligands.
PMID- 10197957
TI - Piperazine imidazo[1,5-a]quinoxaline ureas as high-affinity GABAA ligands of dual
functionality.
AB - A series of imidazo[1,5-a]quinoxaline piperazine ureas appended with a tert-butyl
ester side chain at the 3-position was developed. Analogues within this series
have high affinity for the gamma-aminobutyric acid A (GABAA)/benzodiazepine
receptor complex with efficacies ranging from inverse agonists to full agonists.
Many analogues were found to be partial agonists as indicated by [35S]TBPS and Cl
current ratios. Uniquely, a number of these analogues were found to have a bell
shaped dose-response profile in the alpha1 beta2 gamma2 subtype as determined by
whole cell patch-clamp technique, where in vitro efficacy was found to decrease
with increasing drug concentration. Many of the compounds from this series were
effective in antagonizing metrazole-induced seizures, consistent with
anticonvulsant and possibly anxiolytic activity. Additionally, several analogues
were also effective in lowering cGMP levels (to control values) after applied
stress, also consistent with anxiolytic-like properties. The most effective
compounds in these screens were also active in animal models of anxiety such as
the Vogel and Geller assays. The use of the piperazine substituent allowed for
excellent drug levels and a long duration of action in the central nervous system
for many of the quinoxalines, as determined by ex vivo assay. Pharmacokinetic
analysis of several compounds indicated excellent oral bioavailability and a
reasonable half-life in rats. From this series emerged two partial agonists (55,
91) which had good activity in anxiolytic models, acceptable pharmacokinetics,
and minimal benzodiazepine-type side effects.
PMID- 10197958
TI - Novel potential agents for human cytomegalovirus infection: synthesis and
antiviral activity evaluation of benzothiadiazine dioxide acyclonucleosides.
AB - The first acyclonucleosides based on the benzothiadiazine dioxide system were
synthesized following the silylation procedure. Several acyclic moieties,
including acetoxyethoxymethyl, benzyloxymethyl, and propargyloxymethyl groups,
were introduced. Two synthetic strategies were designed to selectively obtain the
N-1 or N-3 derivatives. Lipase-mediated deacylation was used for the deprotection
of the acyclonucleosides. Some of the benzothiadiazine dioxide acyclonucleosides,
in particular 16, proved active against human cytomegalovirus (CMV) at
concentrations slightly higher than that found for ganciclovir [50% inhibitory
concentration (IC50) = 3. 5-3.7 micrograms/mL, cytotoxicity (CC50) >/= 40
micrograms/mL, MCC = 20 micrograms/mL]. Additionally, compound 16 inhibited the
replication of human immunodeficiency virus type 1 (HIV-1) and HIV-2 in CEM cells
at concentrations that were 5-fold lower than its cytotoxic concentration.
PMID- 10197959
TI - Synthesis, structure-activity relationships, and in vivo evaluations of
substituted di-tert-butylphenols as a novel class of potent, selective, and
orally active cyclooxygenase-2 inhibitors. 1. Thiazolone and oxazolone series.
AB - Selective cyclooxygenase-2 (COX-2) inhibitors have been shown to be potent
antiinflammatory agents with fewer side effects than currently marketed
nonsteroidal antiinflammatory drugs (NSAIDs). Initial mass screening and
subsequent structure-activity relationship (SAR) studies have identified 4b
(PD138387) as the most potent and selective COX-2 inhibitor within the thiazolone
and oxazolone series of di-tert-butylphenols. Compound 4b has an IC50 of 1.7
microM against recombinant human COX-2 and inhibited COX-2 activity in the
J774A.1 cell line with an IC50 of 0.17 microM. It was inactive against purified
ovine COX-1 at 100 microM and did not inhibit COX-1 activity in platelets at 20
microM. Compound 4b was also orally active in vivo with an ED40 of 16 mg/kg in
the carrageenan footpad edema (CFE) assay and caused no gastrointestinal (GI)
damage in rats at the dose of 100 mg/kg but inhibited gastric prostaglandin E2
(PGE2) production in rats' gastric mucosa by 33% following a dose of 100 mg/kg.
The SAR studies of this chemical series revealed that the potency and selectivity
are very sensitive to minor structural changes. A simple isosteric replacement
led to the reversal of selectivity.
PMID- 10197960
TI - Synthesis, structure-activity relationships, and in vivo evaluations of
substituted di-tert-butylphenols as a novel class of potent, selective, and
orally active cyclooxygenase-2 inhibitors. 2. 1,3,4- and 1,2,4-thiadiazole
series.
AB - Two isoforms of the cyclooxygenase (COX) enzyme have been identified: COX-1,
which is expressed constitutively, and COX-2, which is induced in inflammation.
Recently, it has been shown that selective COX-2 inhibitors have antiinflammatory
activity and lack the GI side effects typically associated with NSAIDs. Initial
mass screening and subsequent SAR studies have identified 6b (PD164387) as a
potent, selective, and orally active COX-2 inhibitor. It had IC50 values of 0.14
and 100 microM against recombinant human COX-2 and purified ovine COX-1,
respectively. It inhibited COX-2 activity in the J774A.1 cell line with an IC50
of 0.18 microM and inhibited COX-1 activity in platelets with an IC50 of 3.1
microM. The choline salt of compound 6b was also orally active in vivo with an
ED40 of 7. 1 mg/kg in the carrageenan footpad edema (CFE) assay. In vivo studies
in rats at a dose of 100 mg/kg showed that this compound inhibited gastric
prostaglandin E2 (PGE2) production in gastric mucosa by 77% but caused minimal GI
damage. SAR studies of this chemical series revealed that the potency and
selectivity are very sensitive to minor structural changes.
PMID- 10197961
TI - Design and synthesis of a potent cyclic analogue of the myelin basic protein
epitope MBP72-85: importance of the Ala81 carboxyl group and of a cyclic
conformation for induction of experimental allergic encephalomyelitis.
AB - Experimental allergic encephalomyelitis (EAE) is induced in susceptible animals
by immunodominant determinants of myelin basic protein (MBP), such as guinea pig
sequence MBP72-85. Two linear and one cyclic analogues based on MBP72-85 have
been synthesized and evaluated for EAE induction in Lewis rats. The linear
peptide Gln1-Lys2-Ser3-Gln4-Arg5-Ser6-Gln7-+ ++Asp8-Glu9-Asn10-Pro11-Val12 (1)
was found to induce EAE, while substitution of the Asp residue at position 8 with
Ala resulted in an analogue (2) which suppressed the induction of EAE by its
parent peptide. Nuclear magnetic resonance studies of analogue 1 in dimethyl
sulfoxide (DMSO) using TOCSY/ROESY techniques revealed a head-to-tail
intramolecular interaction (ROE connectivity between betaVal12-gammaGln1),
indicating a pseudocyclic conformation for the immunogenic peptide 1. A
conformational model was developed using NMR constraints and molecular dynamics.
Based on this model, a novel amide-linked cyclic analogue has been designed and
synthesized by connecting the side-chain amino and carboxyl groups of Lys and Glu
at positions 2 and 9, respectively, of linear analogue 1. The cyclic analogue (3)
had similar activity to the linear peptide 1, and the EAE effects induced by
cyclic analogue 3 were completely suppressed by co-injection with the Ala81
substituted analogue 2 in Lewis rats. The similar potencies of analogues 1 and 3
support the proposed cyclic comformation suggested for analogue 1 from NMR
studies and computer modeling and provides the basis for designing more potent
molecules with improved properties such as increased resistance to degradation.15
The present findings suggest that a cyclic conformation for the MBP72-85 epitope
positions the carboxyl group of Asp81 correctly and presumably other side groups
of the peptide such as Arg78 in a manner which enables functional binding of the
trimolecular complex MHC-peptide-T cell receptor resulting in EAE.
PMID- 10197962
TI - Orally active isoxazoline glycoprotein IIb/IIIa antagonists with extended
duration of action.
AB - Modification of the alpha-carbamate substituent of isoxazoline GPIIb/IIIa
(alphaIIb beta3) antagonist DMP 754 (7) led to a series of alpha-sulfonamide and
alpha-sulfamide diaminopropionate isoxazolinylacetamides which were found to be
potent inhibitors of in vitro platelet aggregation. Aryl- and heteroaryl-alpha
sulfonamide groups, in conjunction with (5R)-isoxazoline (2S)-diaminopropionate
stereochemistry, were found to impart a pronounced duration of antiplatelet
effect in dogs, potentially due to high affinity for unactivated platelets.
Isoxazolylsulfonamide 34b (DMP 802), a highly selective GPIIb/IIIa antagonist,
demonstrated a prolonged duration of action after iv and po dosing and high
affinity for resting and activated platelets. The prolonged antiplatelet profile
of DMP 802 in dogs and the high affinity of DMP 802 for human platelets may be
predictive of clinical utility as a once-daily antiplatelet agent.
PMID- 10197963
TI - Synthesis and in vitro pharmacology of a series of new chiral histamine H3
receptor ligands: 2-(R and S)-Amino-3-(1H-imidazol-4(5)-yl)propyl ether
derivatives.
AB - To investigate stereospecificity and the mechanism of activation of the histamine
H3-receptor, a series of 2-(R and S)-amino-3-(1H-imidazol-4(5)-yl)propyl ether
derivatives were synthesized. In these compounds, the structures of the well
known antagonist iodoproxyfan and the full agonists R- or S-(alpha)
methylhistamine were combined in one molecule. The obtained "hybrid" molecules
were tested for H3-receptor affinity on rat cerebral cortex. Some selected
compounds were further screened for H3-receptor functional activity with
GTPgamma[35S] autoradiography studies using rat brain tissue sections. The
affinity of all the synthesized compounds (-log Ki = 5.9-7.9) was lower than that
found for iodoproxyfan or two of its analogues; however, the compounds showed
stereospecificity. The S-configuration of the series of 2-amino-3-(1H-imidazol
4(5)-yl)propyl ether derivatives, which resembles the stereochemistry of R
(alpha)-methylhistamine, was more favorable. Incorporation of an amino group in
the propyl chain of iodoproxyfan and analogues did not alter the antagonistic
behavior for compounds with an aromatic side chain. However, when also the
aromatic moiety was replaced by a cyclohexyl group, the compounds behaved as
agonists. This indicates that an interaction between the side chain amino group
and the H3-receptor protein is involved in H3-receptor activation. The 2-(S)
amino-3-(1H-imidazol-4(5)-yl)propyl cyclohexylmethyl ether (23) has H3-receptor
agonistic properties with high affinity for the histamine H3-receptor (-log Ki =
7.9 +/- 0.2) and might serve as a useful tool for further studies concerning drug
design and receptor-ligand interactions.
PMID- 10197964
TI - Structure-based design, synthesis, and biological evaluation of irreversible
human rhinovirus 3C protease inhibitors. 3. Structure-activity studies of
ketomethylene-containing peptidomimetics.
AB - The structure-based design, chemical synthesis, and biological evaluation of
various ketomethylene-containing human rhinovirus (HRV) 3C protease (3CP)
inhibitors are described. These compounds are comprised of a peptidomimetic
binding determinant and an ethyl propenoate Michael acceptor moiety which forms
an irreversible covalent adduct with the active site cysteine residue of the 3C
enzyme. The ketomethylene-containing inhibitors typically display slightly
reduced 3CP inhibition activity relative to the corresponding peptide-derived
molecules, but they also exhibit significantly improved antiviral properties.
Optimization of the ketomethylene-containing compounds is shown to provide
several highly active 3C protease inhibitors which function as potent
antirhinoviral agents (EC90 = <1 microM) against multiple virus serotypes in cell
culture.
PMID- 10197965
TI - Structure-based design, synthesis, and biological evaluation of irreversible
human rhinovirus 3C protease inhibitors. 4. Incorporation of P1 lactam moieties
as L-glutamine replacements.
AB - The structure-based design, chemical synthesis, and biological evaluation of
various human rhinovirus (HRV) 3C protease (3CP) inhibitors which incorporate P1
lactam moieties in lieu of an L-glutamine residue are described. These compounds
are comprised of a tripeptidyl or peptidomimetic binding determinant and an ethyl
propenoate Michael acceptor moiety which forms an irreversible covalent adduct
with the active site cysteine residue of the 3C enzyme. The P1-lactam-containing
inhibitors display significantly increased 3CP inhibition activity along with
improved antirhinoviral properties relative to corresponding L-glutamine-derived
molecules. In addition, several lactam-containing compounds exhibit excellent
selectivity for HRV 3CP over several other serine and cysteine proteases and are
not appreciably degraded by a variety of biological agents. One of the most
potent inhibitors (AG7088, mean antirhinoviral EC90 approximately 0.10 microM, n
= 46 serotypes) is shown to warrant additional preclinical development to explore
its potential for use as an antirhinoviral agent.
PMID- 10197966
TI - Binding preferences of hydroxamate inhibitors of the matrix metalloproteinase
human fibroblast collagenase.
AB - In this paper we report molecular dynamics (MD) and free energy perturbation
(FEP) studies carried out on enzyme-inhibitor (two hydroxamates that only differ
by a carbon-carbon double bond) complexes of human fibroblast collagenase to
obtain insights into the structural and energetic preferences of these
inhibitors. We have developed a bonded model for the catalytic and structural
zinc centers (Hoops, S. C.; et al. J. Am. Chem. Soc. 1991, 113, 8262-8270) where
the electrostatic representation for this model was derived using a novel quantum
mechanical/molecular-mechanical (QM/MM) minimization procedure followed by
electrostatic potential fitting. The resulting bonded model for the zinc ions was
then used to generate MD trajectories for structural analysis and FEP studies.
This model has satisfactorily reproduced the structural features of the active
site, and furthermore, the FEP simulations gave relative free energies of binding
in good agreement with experimental results. MD simulations in conjunction with
the FEP are able to provide a structural explanation regarding why one
hydroxamate inhibitor is favored over the other, and we are also able to make
predictions about changes in the inhibitor that would enhance protein-inhibitor
interactions.
PMID- 10197967
TI - Guanidine derivatives as combined thromboxane A2 receptor antagonists and
synthase inhibitors.
AB - A new series of omega-disubstituted alkenoic acid derivatives derived from
samixogrel 5 were designed and synthesized as combined thromboxane A2 receptor
antagonists/thromboxane A2 synthase inhibitors with improved solubility and
reduced protein binding compared to 5. Hexenoic acid derivatives with a 3-pyridyl
group and 3-(2-cyano-3-alkyl-guanidino)phenyl substituent were found to be
optimal with regard to this dual mode of action. The most potent compound, E-6-(3
(2-cyano-3-tert-butyl-guanidino)phenyl)-6-(3-pyridyl)hex-5-eno ic acid,
"terbogrel" 32 inhibits the thromboxane A2 synthase in human gel-filtered
platelets with an IC50 value of 4.0 +/- 0.5 nM (n = 4). Radioligand binding
studies with 3H-SQ 29,548 revealed that 32 blocks the thromboxane A2/endoperoxide
receptor on washed human platelets with an IC50 of 11 +/- 6 nM (n = 2) and with
an IC50 of 38 +/- 1 nM (n = 15) in platelet-rich plasma. Terbogrel inhibits the
collagen-induced platelet aggregation in human platelet-rich plasma and whole
blood with an IC50 of 310 +/- 18 nM (n = 8) and 52 +/- 20 nM (n = 6),
respectively. This was shown to translate into a potent antithrombotic effect in
vivo as demonstrated in studies using a model of arterial thrombosis in rabbits
(ED50 = 0.19 +/- 0.07 mg/kg; n = 20). Thus, terbogrel is the first compound with
a guanidino moiety demonstrating both a potent TXA2 synthase inhibition and a
potent TXA2 receptor antagonism and has been selected for further clinical
development.
PMID- 10197968
TI - Docking of cationic antibiotics to negatively charged pockets in RNA folds.
AB - The binding of aminoglycosides to RNA provides a paradigm system for the analysis
of RNA-drug interactions. The electrostatic field around three-dimensional RNA
folds creates localized and defined negatively charged regions which are
potential docking sites for the cationic ammonium groups of aminoglycosides. To
explore in RNA folds the electronegative pockets suitable for aminoglycoside
binding, we used calculations of the electrostatic field and Brownian dynamics
simulations of cation diffusion. We applied the technique on those RNA molecules
experimentally known to bind aminoglycosides, namely, two tobramycin aptamers
(Wang, Y.; Rando, R. R. Chem. Biol. 1995, 2, 281-290): the aminoglycoside-binding
region in 16S ribosomal RNA (Moazed, S.; Noller, H. F. Nature 1987, 327, 389-394)
and the TAR RNA from human immunodeficiency virus (Mei, H.-Y.; et al. Bioorg.
Med. Chem. Lett. 1995, 5, 2755-2760). For the aptamers and ribosomal RNA, for
which the binding sites of the aminoglycosides are known, a good agreement
between negatively charged pockets and the binding positions of the drugs was
found. On the basis of variations between neomycin-like and kanamycin-like
aminoglycosides in the interaction with the electrostatic field of ribosomal RNA,
we propose a model for the different binding specificities of these two classes
of drugs. The spatial congruence between the electronegative pockets in RNA folds
and binding positions of aminoglycosides was used to dock aminoglycosides to
ribosomal and TAR RNAs. Molecular dynamics simulations were used to analyze
possible RNA-drug interactions. Aminoglycosides inhibit the binding of the viral
Tat protein to TAR RNA; however, the drug-binding sites are still unknown. Thus,
our docking approach provides first structural models for TAR-aminoglycoside
complexes. The RNA-drug interactions observed in the modeled complexes support
the view that the antibiotics might lock TAR in a conformation with low affinity
for the Tat protein, explaining the experimentally found aminoglycoside
inhibition of the Tat-TAR interaction (Mei, H.-Y.; et al. Bioorg. Med. Chem.
Lett. 1995, 5, 2755-2760).
PMID- 10197969
TI - Enzyme-assisted total synthesis of the optical antipodes D-myo-inositol 3,4,5
trisphosphate and D-myo-inositol 1,5, 6-trisphosphate: aspects of their structure
activity relationship to biologically active inositol phosphates.
AB - Unambiguous total syntheses of both optical antipodes of the enantiomeric pair D
myo-inositol 3,4,5-trisphosphate (Ins(3,4,5)P3) and D-myo-inositol 1,5,6
trisphosphate (Ins(1,5,6)P3) are described. The ring system characteristic of myo
inositol was constructed de novo from p-benzoquinone. X-ray data for the
enzymatically resolved (1S,2R,3R,4S)-1,4-diacetoxy-2,3-dibromocyclohex-5-ene
enabled the unequivocal assignment of the absolute configuration. Subsequent
transformations under stereocontrolled conditions led to enantiopure C2
symmetrical 1,4-(di-O-benzyldiphospho)conduritol B derivatives. Their synthetic
potential was exploited to prepare Ins(3,4,5,6)P4 and Ins(1,4,5,6)P4 in three
steps. With a recently identified and partially purified InsP5/InsP4
phosphohydrolase from Dictyostelium discoideum, these enantiomers could be
converted to the target compounds, Ins(3,4,5)P3 and Ins(1,5,6)P3, on a
preparative scale. An HPLC system employed for both purification of the inositol
phosphates and analytical runs ensured that the products were isomerically
homogeneous. The sensitivity of detection achieved by a complexometric postcolumn
derivatization method indicates that the complexation properties of
Ins(3,4,5)P3/Ins(1,5,6)P3 resemble those of Ins(1,2,3)P3, a compound with
antioxidant potential. The set of inositol phosphates synthesized was used to
clarify structural motifs important for molecular recognition by p42(IP4), a high
affinity Ins(1,3,4,5)P4/PtdIns(3,4,5)P3-specific binding protein from pig
cerebellum.
PMID- 10197971
TI - Synthesis and biological evaluation of boron-containing polyamines as potential
agents for neutron capture therapy of brain tumors.
AB - New boron-containing spermidine/spermine (SPD/SPM) analogues have been
synthesized: N5-[4-(2-aminoethyl-o-carboranyl)butyl] and N5-{4-[(2,3
dihydroxypropyl)-o-carboranyl]butyl} SPD/SPM derivatives (ASPD-5, ASPM-5, DHSPD
5, and DHSPM-5) as well as N5-{[4-(dihydroxyboryl)phenyl]methyl}spermidine (BBSPD
5). These boronated polyamines retain their ability to displace ethidium bromide
from calf thymus DNA and are rapidly taken up in vitro by F98 rat glioma cells.
The in vitro toxicities of ASPD-5, ASPM-5, DHSPD-5, and DHSPM-5 are lower than
those previously reported for N5-[4-(o-carboranyl)butyl] SPD/SPM derivatives (SPD
5 and SPM-5) but similar to those of native SPD and SPM. Very low toxicity was
also observed for BBSPD-5. In vivo studies of ASPD-5 and BBSPD-5 were performed
in mice bearing intracerebral implants of the GL261 glioma and subcutaneous
implants of the B16 melanoma. The biodistribution data found in both tumor models
suggest that the polyamines synthesized to date do not appear to be suitable
boron agents for BNCT.
PMID- 10197970
TI - 2,3-Diarylcyclopentenones as orally active, highly selective cyclooxygenase-2
inhibitors.
AB - Cyclopentenones containing a 4-(methylsulfonyl)phenyl group in the 3-position and
a phenyl ring in the 2-position are selective inhibitors of cyclooxygenase-2 (COX
2). The selectivity for COX-2 over COX-1 is dramatically improved by substituting
the 2-phenyl group with halogens in the meta position or by replacing the phenyl
ring with a 2- or 3-pyridyl ring. Thus the 3,5-difluorophenyl derivative 7 (L
776,967) and the 3-pyridyl derivative 13 (L-784,506) are particularly interesting
as potential antiinflammatory agents with reduced side-effect profiles. Both
exhibit good oral bioavailability and are potent in standard models of pain,
fever, and inflammation yet have a much reduced effect on the GI integrity of
rats compared to standard nonsteroidal antiflammatory drugs.
PMID- 10197972
TI - 1-Arylnaphthalene lignan: a novel scaffold for type 5 phosphodiesterase
inhibitor.
AB - 1-Arylnaphthalene lignan, which had been reported as a PDE4 inhibitor by Iwasaki,
was disclosed as a new structural class of PDE5 inhibitors. The structural
requirements for potent and specific PDE5 inhibition were revealed in a 1
arylnaphthalene lignan series, in which 1-(3-bromo-4, 5-dimethoxyphenyl)-5-chloro
3-[4-(2-hydroxyethyl)-1-piperazinylcarbon yl]-2-(methoxycarbonyl)naphthalene
hydrochloride (27q) showed the most potent and specific inhibition (PDE5
inhibition IC50 = 6.2 nM, selectivity for PDE5 against PDE1, -2, -3, and -4 >16
000). It is noteworthy that 27q has the best selectivities against PDE isoforms
among PDE5 inhibitors so far reported. Compound 27q exhibited almost the same
relaxant effects on rat aortic rings as sodium 1-[6-chloro-4-[(3, 4
methylenedioxybenzyl)amino]quinazolin-2-yl]piperidine-4-ca rboxylate (35) (27q,
EC50 = 0.10 microM; 35, EC50 = 0.20 microM) and was selected for further
biological evaluation.
PMID- 10197973
TI - Quinuclidine inhibitors of 2,3-oxidosqualene cyclase-lanosterol synthase:
optimization from lipid profiles.
AB - Novel 3-substituted quinuclidine inhibitors of cholesterol biosynthesis are
reported. Compounds were optimized against oxidosqualene cyclase-lanosterol
synthase (OSC) inhibition in vivo, rather than by the conventional optimization
of structure-activity relationship information based on in vitro OSC inhibition.
Thus, examination of HPLC lipid profiles from orally dosed rats showed
cholesterol biosynthetic intermediates and whether cholesterol levels were
reduced. A new substituted quinuclidine pharmacophore 18a-c was rapidly found for
the inhibition of OSC, and the most promising inhibitors were validated by the
confirmation of potent OSC inhibition. Compound 16 gave an IC50 value of 83 +/-
11 nM for human and an IC50 value of 124 +/- 14 nM, for rat, coupled with oral
and selective inhibition of cholesterol biosynthesis derived from OSC inhibition
(rat, ED50 = 1.3 +/- 0.7 mg/kg, n = 5; marmoset, 15 mg/kg dose, n = 3, caused
complete inhibition). These 3-substituted quinuclidines, which were derived from
a quinuclidine series previously known to inhibit cholesterol biosynthesis at the
squalene synthase step, may afford a novel series of hypocholesterolemic agents
acting by the inhibition of OSC.
PMID- 10197974
TI - Fluorescent pseudo-peptide linear vasopressin antagonists: design, synthesis, and
applications.
AB - Fluoresceinyl and rhodamyl groups have been coupled by an amide link to side
chain amino groups at positions 1, 6, and 8 of pseudo-peptide linear vasopressin
antagonists (Manning et al. Int. J. Pept. Protein Res. 1992, 40, 261-267) through
different positions on the fluorophore, to give tetraethylrhodamyl-DTyr(Me)-Phe
Gln-Asn-Arg-Pro-Arg-Tyr-NH2 (2), 4-HOPh(CH2)2CO-DTyr(Me)-Phe-Gln-Asn-Lys(5
carboxyfl uoresceinyl)-Pro-A rg-NH2 (4), 4-HOPh(CH2)2CO-DTyr(Me)-Phe-Gln-Asn
Lys(5- or 6-carboxytetramethylrhodamyl)-Pro-Arg-NH2 (5, 6), 4-HOPh(CH2)2CO
DTyr(Me)-Phe-Gln-Asn-Arg-Pro-Lys(5- or 6- carboxyfluoresceinyl)-NH2 (8, 9), and 4
HOPh(CH2)2CO-DTyr(Me)-Phe-Gln-Asn-Arg-Pro-Lys(5- or 6-
carboxytetramethylrhodamyl)-NH2 (10, 11). The closer to the C-terminus the
fluorophore, the higher the affinities of the fluorescent derivatives for the
human vasopressin V1a receptor transfected in CHO cells. The compound 10 has a Ki
of 70 pM, as determined by competition experiments with [125I]-4-HOPhCH2CO
DTyr(Me)-Phe-Gln-Asn-Arg-Pro-Arg-NH2. It showed a good selectivity for human V1a
receptor versus human OT (Ki = 1.2 nM), human vasopressin V1b (Ki approximately
27 nM), and human vasopressin V2 (Ki > 5000 nM) receptor subtypes. All
fluorescent analogues were antagonists as shown by the inhibition of vasopressin
induced inositol phosphate accumulation. These fluorescent ligands are efficient
for labeling cells expressing the human V1a receptor subtype, as shown by flow
cytofluorometric experiments or fluorescence microscopy. They are also
appropriate tools for structural analysis of the vasopressin receptors by
fluorescence.
PMID- 10197975
TI - Synthesis and anti-HIV and anti-HBV activities of 2'-fluoro-2', 3'-unsaturated L
nucleosides.
AB - The synthesis of L-nucleoside analogues containing 2'-vinylic fluoride was
accomplished by direct condensation method, and their anti-HIV and anti-HBV
activities were evaluated in vitro. The key intermediate 8, the sugar moiety of
our target compounds, was prepared from 1,2-O-isopropylidene-L-glyceraldehyde via
(R)-2-fluorobutenolide intermediate 5 in five steps. Coupling of the acetate 8
with the appropriate heterocycles (silylated uracil, thymine, N4-benzoylcytosine,
N4-benzoyl-5-fluorocytosine, 6-chloropurine, and 6-chloro-2-fluoropurine) in the
presence of Lewis acid afforded a series of 2'-fluorinated L-nucleoside analogues
(15-18, 23-26, 36-45). The newly synthesized compounds were evaluated for their
antiviral activities against HIV-1 in human peripheral blood mononuclear (PBM)
cells and HBV in 2.2.15 cells. Cytosine 23, 5-fluorocytosine 25, and adenine 36
derivatives exhibited moderate to potent anti-HIV (EC50 0.51, 0.17, and 1.5
microM, respectively) and anti-HBV (EC50 0.18, 0.225, and 1.7 microM,
respectively) activities without significant cytotoxicity up to 100 microM in
human PBM, Vero, CEM, and HepG2 cells.
PMID- 10197976
TI - Mammalian sex determination: a molecular drama.
PMID- 10197977
TI - Molecular mechanism of nucleotide excision repair.
PMID- 10197978
TI - SHIP is a negative regulator of growth factor receptor-mediated PKB/Akt
activation and myeloid cell survival.
AB - SHIP is an inositol 5' phosphatase that hydrolyzes the PI3'K product PI(3,4,5)P3.
We show that SHIP-deficient mice exhibit dramatic chronic hyperplasia of myeloid
cells resulting in splenomegaly, lymphadenopathy, and myeloid infiltration of
vital organs. Neutrophils and bone marrow-derived mast cells from SHIP-/- mice
are less susceptible to programmed cell death induced by various apoptotic
stimuli or by growth factor withdrawal. Engagement of IL3-R and GM-CSF-R in these
cells leads to increased and prolonged PI3'K-dependent PI(3,4,5)P3 accumulation
and PKB activation. These data indicate that SHIP is a negative regulator of
growth factor-mediated PKB activation and myeloid cell survival.
PMID- 10197979
TI - Toll receptor-mediated Drosophila immune response requires Dif, an NF-kappaB
factor.
AB - The induction of immunity genes in Drosophila has been proposed to be dependent
on Dorsal, Dif, and Relish, the NF-kappaB-related factors. Here we provide
genetic evidence that Dif is required for the induction of only a subset of
antimicrobial peptide genes. The results show that the presence of Dif without
Dorsal is sufficient to mediate the induction of drosomycin and defensin. We also
demonstrate that Dif is a downstream component of the Toll signaling pathway in
activating the drosomycin expression. These results reveal that individual
members of the NF-kappaB family in Drosophila have distinct roles in immunity and
development.
PMID- 10197980
TI - Yeast calcineurin regulates nuclear localization of the Crz1p transcription
factor through dephosphorylation.
AB - Calcineurin, a Ca2+/calmodulin dependent protein phosphatase, regulates Ca2+
dependent processes in a wide variety of cells. In the yeast, Saccharomyces
cerevisiae, calcineurin effects Ca2+-dependent changes in gene expression through
regulation of the Crz1p transcription factor. We show here that calcineurin
dephosphorylates Crz1p and that this results in translocation of Crz1p to the
nucleus. We identify a region of Crz1p that is required for calcineurin-dependent
regulation of its phosphorylation, localization, and activity, and show that this
region has significant sequence simlarity to a portion of NF-AT, a family of
mammalian transcription factors whose localization is also regulated by
calcineurin. Thus, the mechanism of Ca2+/calcineurin-dependent signaling shows
remarkable conservation between yeast and mammalian cells.
PMID- 10197981
TI - A mechanism of repression of TGFbeta/ Smad signaling by oncogenic Ras.
AB - TGFbeta can override the proliferative effects of EGF and other Ras-activating
mitogens in normal epithelial cells. However, epithelial cells harboring
oncogenic Ras mutations often show a loss of TGFbeta antimitogenic responses.
Here we report that oncogenic Ras inhibits TGFbeta signaling in mammary and lung
epithelial cells by negatively regulating the TGFbeta mediators Smad2 and Smad3.
Oncogenically activated Ras inhibits the TGFbeta-induced nuclear accumulation of
Smad2 and Smad3 and Smad-dependent transcription. Ras acting via Erk MAP kinases
causes phosphorylation of Smad2 and Smad3 at specific sites in the region linking
the DNA-binding domain and the transcriptional activation domain. These sites are
separate from the TGFbeta receptor phosphorylation sites that activate Smad
nuclear translocation. Mutation of these MAP kinase sites in Smad3 yields a Ras
resistant form that can rescue the growth inhibitory response to TGFbeta in Ras
transformed cells. EGF, which is weaker than oncogenic mutations at activating
Ras, induces a less extensive phosphorylation and cytoplasmic retention of Smad2
and Smad3. Our results suggest a mechanism for the counterbalanced regulation of
Smad2/Smad3 by TGFbeta and Ras signals in normal cells, and for the silencing of
antimitogenic TGFbeta functions by hyperactive Ras in cancer cells.
PMID- 10197982
TI - Functional requirement of p23 and Hsp90 in telomerase complexes.
AB - Most normal human diploid cells have no detectable telomerase; however,
expression of the catalytic subunit of telomerase is sufficient to induce
telomerase activity and, in many cases, will bypass normal senescence. We and
others have previously demonstrated in vitro assembly of active telomerase by
combining the purified RNA component with the reverse transcriptase catalytic
component synthesized in rabbit reticulocyte extract. Here we show that assembly
of active telomerase from in vitro-synthesized components requires the
contribution of proteins present in reticulocyte extracts. We have identified the
molecular chaperones p23 and Hsp90 as proteins that bind to the catalytic subunit
of telomerase. Blockade of this interaction inhibits assembly of active
telomerase in vitro. Also, a significant fraction of active telomerase from cell
extracts is associated with p23 and Hsp90. Consistent with in vitro results,
inhibition of Hsp90 function in cells blocks assembly of active telomerase. To
our knowledge, p23 and Hsp90 are the first telomerase-associated proteins
demonstrated to contribute to telomerase activity.
PMID- 10197983
TI - ORC localization in Drosophila follicle cells and the effects of mutations in
dE2F and dDP.
AB - We isolated mutations in Drosophila E2F and DP that affect chorion gene
amplification and ORC2 localization in the follicle cells. In the follicle cells
of the ovary, the ORC2 protein is localized throughout the follicle cell nuclei
when they are undergoing polyploid genomic replication, and its levels appear
constant in both S and G phases. In contrast, when genomic replication ceases and
specific regions amplify, ORC2 is present solely at the amplifying loci.
Mutations in the DNA-binding domains of dE2F or dDP reduce amplification, and in
these mutants specific localization of ORC2 to amplification loci is lost.
Interestingly, a dE2F mutant predicted to lack the carboxy-terminal
transcriptional activation and RB-binding domain does not abolish ORC2
localization and shows premature chorion amplification. The effect of the
mutations in the heterodimer subunits suggests that E2F controls not only the
onset of S phase but also origin activity within S phase.
PMID- 10197985
TI - Initial recognition of U12-dependent introns requires both U11/5' splice-site and
U12/branchpoint interactions.
AB - We have investigated the formation of prespliceosomal complex A in HeLa nuclear
extracts on a splicing substrate containing an AT-AC (U12-type) intron from the
P120 gene. Using an RNase H protection assay and specific blocking
oligonucleotides, we find that recognition of the 5' splice-site (5'ss) and
branchpoint sequence (BPS) elements by U11 and U12 snRNPs, respectively, displays
strong cooperativity, requiring both sites in the pre-mRNA substrate for
efficient complex formation. Deletion analysis indicates that beside the 5'ss and
BPS, no additional elements in the pre-mRNA are necessary for A-complex
formation, although 5' exon sequences provide stimulation. Cross-linking studies
with pre-mRNAs containing the 5'ss or BPS alone indicate that recognition of the
BPS by the U12 snRNP is stimulated at least 20- to 30-fold by the binding of the
U11 snRNP to the 5'ss in the same pre-mRNA molecule, whereas recognition of the
5'ss by U11 is stimulated approximately fivefold by the U12/BPS interaction.
These results argue that intron recognition in the U12-dependent splicing pathway
is carried out by a single U11/U12 di-snRNP complex, suggesting greater rigidity
in the intron recognition process than in the major spliceosome.
PMID- 10197984
TI - Human step II splicing factor hSlu7 functions in restructuring the spliceosome
between the catalytic steps of splicing.
AB - The spliceosome catalyzes pre-mRNA splicing in two steps. After catalytic step I,
a major remodeling of the spliceosome occurs to establish the active site for
step II. Here, we report the isolation of a cDNA encoding hSlu7, the human
homolog of the yeast second step splicing factor Slu7. We show that hSlu7
associates with the spliceosome late in the splicing pathway, but at a stage
prior to recognition of the 3' splice site for step II. In the absence of hSlu7,
splicing is stalled between the catalytic steps in a novel complex, the
CDeltahSlu7 complex. We provide evidence that this complex differs significantly
in structure from the known spliceosomal complexes, yet is a functional
intermediate between the catalytic steps of splicing. Together, our observations
indicate that hSlu7 is required for a structural alteration of the spliceosome
prior to the establishment of the catalytically active spliceosome for step II.
PMID- 10197986
TI - Specific isoforms of squid, a Drosophila hnRNP, perform distinct roles in Gurken
localization during oogenesis.
AB - Heterogeneous nuclear RNA-binding proteins, hnRNPs, have been implicated in
nuclear export of mRNAs in organisms from yeast to humans. A germ-line mutation
in a Drosophila hnRNP, Squid (Sqd)/hrp40, causes female sterility as a result of
mislocalization of gurken (grk) mRNA during oogenesis. Alternative splicing
produces three isoforms, SqdA, SqdB, and SqdS. Here we show that these isoforms
are not equivalent; SqdA and SqdS perform overlapping but nonidentical functions
in grk mRNA localization and protein accumulation, whereas SqdB cannot perform
these functions. Furthermore, although all three Sqd isoforms are expressed in
the germline cells of the ovary, they display distinct intracellular
distributions. Both SqdB and SqdS are detected in germ-line nuclei, whereas SqdA
is predominantly cytoplasmic. We show that this differential nuclear accumulation
is correlated with a differential association with the nuclear import protein
Transportin. Finally, we provide evidence that grk mRNA localization and
translation are coupled by an interaction between Sqd and the translational
repressor protein Bruno. These results demonstrate the isoform-specific
contributions of individual hnRNP proteins in the regulation of a specific mRNA.
Moreover, these data suggest a novel role for hnRNPs in localization and
translational regulation of mRNAs.
PMID- 10197987
TI - An HMG1-like protein facilitates Wnt signaling in Caenorhabditis elegans.
AB - We show that during Caenorhabditis elegans male spicule development, the
specification of a glial versus neuronal cell fate in a canonical neurogenic
sublineage is dependent on Wnt signaling. Inactivation of a Wnt signaling pathway
mediated by the Wnt receptor LIN-17 transforms the SPD sheath cell into its
sister, the SPD neuron. We discovered a new mutant, son-1, that displays this
same cell fate transformation. The son-1 mutation enhances the phenotypes of
reduction-of-function lin-17 mutants in several developmental processes,
including vulva development, somatic gonad development, and male tail patterning.
son-1 encodes an HMG1/2-like DNA-binding protein and is localized in all cell
nuclei through development as revealed by a GFP reporter construct. Disruption of
son-1 function by RNA-mediated interference results in the same spicule defect as
caused by overexpression of POP-1, a TCF/LEF class HMG protein known to act
downstream of the Wnt signaling pathway. Our results provide in vivo evidence for
the functional involvement of an HMG1/2-like protein, SON-1, in Wnt signaling.
The sequence nonspecific HMG protein SON-1 and the sequence specific HMG protein
POP-1 might both act in the Wnt responding cells to regulate gene transcription
in opposite directions.
PMID- 10197988
TI - Regulation of homologous recombination: Chi inactivates RecBCD enzyme by
disassembly of the three subunits.
AB - We report here an unusual mechanism for enzyme regulation: the disassembly of all
three subunits of RecBCD enzyme after its interaction with a Chi recombination
hot spot. The enzyme, which is essential for the major pathway of recombination
in Escherichia coli, acts on linear double-stranded DNA bearing a Chi site to
produce single-stranded DNA substrates for strand exchange by RecA protein. We
show that after reaction with DNA bearing Chi sites, RecBCD enzyme is inactivated
and the three subunits migrate as separate species during glycerol gradient
ultracentrifugation or native gel electrophoresis. This Chi-mediated inactivation
and disassembly of purified RecBCD enzyme can account for the previously reported
Chi-dependent loss of Chi activity in E. coli cells containing broken DNA. Our
results support a model of recombination in which Chi regulates one RecBCD enzyme
molecule to make a single recombinational exchange ('one enzyme-one exchange'
hypothesis).
PMID- 10197990
TI - NahW, a novel, inducible salicylate hydroxylase involved in mineralization of
naphthalene by Pseudomonas stutzeri AN10.
AB - Two genes, nahG and nahW, encoding two independent salicylate 1-hydroxylases have
been identified in the naphthalene-degrading strain Pseudomonas stutzeri AN10.
While nahG resides in the same transcriptional unit as the meta-cleavage pathway
genes, forming the naphthalene degradation lower pathway, nahW is situated
outside but in close proximity to this transcriptional unit. The nahG and nahW
genes of P. stutzeri AN10 are induced and expressed upon incubation with
salicylate, and the enzymes that are encoded, NahG and NahW, are involved in
naphthalene and salicylate metabolism. Both genes, nahG and nahW, have been
cloned in Escherichia coli JM109. The overexpression of these genes yields
peptides with apparent molecular masses of 46 kDa (NahG) and 43 kDa (NahW),
respectively. Both enzymes exhibit broad substrate specificities and metabolize
salicylate, methylsalicylates, and chlorosalicylates. However, the relative rates
by which the substituted analogs are transformed differ considerably.
PMID- 10197989
TI - The RecBC enzyme loads RecA protein onto ssDNA asymmetrically and independently
of chi, resulting in constitutive recombination activation.
AB - Double-strand DNA break repair and homologous recombination in Escherichia coli
proceed by the RecBCD pathway, which is regulated by cis-acting elements known as
chi sites. A crucial feature of this regulation is the RecBCD enzyme-directed
loading of RecA protein specifically onto the 3'-terminal, chi-containing DNA
strand. Here we show that RecBC enzyme (lacking the RecD subunit) loads RecA
protein constitutively onto the 3'-terminal DNA strand, with no requirement for
chi. This strand is preferentially utilized in homologous pairing reactions. We
propose that RecA protein loading is a latent property of the RecBCD holoenzyme,
which is normally blocked by the RecD subunit and is revealed following
interaction with chi.
PMID- 10197991
TI - The blue copper-containing nitrite reductase from Alcaligenes xylosoxidans:
cloning of the nirA gene and characterization of the recombinant enzyme.
AB - The nirA gene encoding the blue dissimilatory nitrite reductase from Alcaligenes
xylosoxidans has been cloned and sequenced. To our knowledge, this is the first
report of the characterization of a gene encoding a blue copper-containing
nitrite reductase. The deduced amino acid sequence exhibits a high degree of
similarity to other copper-containing nitrite reductases from various bacterial
sources. The full-length protein included a 24-amino-acid leader peptide. The
nirA gene was overexpressed in Escherichia coli and was shown to be exported to
the periplasm. Purification was achieved in a single step, and analysis of the
recombinant Nir enzyme revealed that cleavage of the signal peptide occurred at a
position identical to that for the native enzyme isolated from A. xylosoxidans.
The recombinant Nir isolated directly was blue and trimeric and, on the basis of
electron paramagnetic resonance spectroscopy and metal analysis, possessed only
type 1 copper centers. This type 2-depleted enzyme preparation also had a low
nitrite reductase enzyme activity. Incubation of the periplasmic fraction with
copper sulfate prior to purification resulted in the isolation of an enzyme with
a full complement of type 1 and type 2 copper centers and a high specific
activity. The kinetic properties of the recombinant enzyme were indistinguishable
from those of the native nitrite reductase isolated from A. xylosoxidans. This
rapid isolation procedure will greatly facilitate genetic and biochemical
characterization of both wild-type and mutant derivatives of this protein.
PMID- 10197992
TI - RecD function is required for high-pressure growth of a deep-sea bacterium.
AB - A genomic library derived from the deep-sea bacterium Photobacterium profundum
SS9 was conjugally delivered into a previously isolated pressure-sensitive SS9
mutant, designated EC1002 (E. Chi and D. H. Bartlett, J. Bacteriol. 175:7533
7540, 1993), and exconjugants were screened for the ability to grow at 280-atm
hydrostatic pressure. Several clones were identified that had restored high
pressure growth. The complementing DNA was localized and in all cases found to
possess strong homology to recD, a DNA recombination and repair gene. EC1002 was
found to be deficient in plasmid stability, a phenotype also seen in Escherichia
coli recD mutants. The defect in EC1002 was localized to a point mutation that
created a stop codon within the recD gene. Two additional recD mutants were
constructed by gene disruption and were both found to possess a pressure
sensitive growth phenotype, although the magnitude of the defect depended on the
extent of 3' truncation of the recD coding sequence. Surprisingly, the
introduction of the SS9 recD gene into an E. coli recD mutant had two dramatic
effects. At high pressure, SS9 recD enabled growth in the E. coli mutant strain
under conditions of plasmid antibiotic resistance selection and prevented cell
filamentation. Both of these effects were recessive to wild-type E. coli recD.
These results suggest that the SS9 recD gene plays an essential role in SS9
growth at high pressure and that it may be possible to identify additional
aspects of RecD function through the characterization of this activity.
PMID- 10197993
TI - Specific contacts between residues in the DNA-binding domain of the TyrR protein
and bases in the operator of the tyrP gene of Escherichia coli.
AB - In the presence of tyrosine, the TyrR protein of Escherichia coli represses the
expression of the tyrP gene by binding to the double TyrR boxes which overlap the
promoter. Previously, we have carried out methylation, uracil, and ethylation
interference experiments and have identified both guanine and thymine bases and
phosphates within the TyrR box sequences that are contacted by the TyrR protein
(J. S. Hwang, J. Yang, and A. J. Pittard, J. Bacteriol. 179:1051-1058, 1997). In
this study, we have used missing contact probing to test the involvement of all
of the bases within the tyrP operator in the binding of TyrR. Our results
indicate that nearly all the bases within the palindromic arms of the strong and
weak boxes are important for the binding of the TyrR protein. Two alanine
substituted mutant TyrR proteins, HA494 and TA495, were purified, and their
binding affinities for the tyrP operator were measured by a gel shift assay.
HA494 was shown to be completely defective in binding to the tyrP operator in
vitro, while, in comparison with wild-Type TyrR, TA495 had only a small reduction
in DNA binding. Missing contact probing was performed by using the purified TA495
protein, and the results suggest that T495 makes specific contacts with adenine
and thymine bases at the +/-5 positions in the TyrR boxes.
PMID- 10197994
TI - Replacement of vegetative sigmaA by sporulation-specific sigmaF as a component of
the RNA polymerase holoenzyme in sporulating Bacillus subtilis.
AB - Soon after asymmetric septation in sporulating Bacillus subtilis cells, sigmaF is
liberated in the prespore from inhibition by SpoIIAB. To initiate transcription
from its cognate promoters, sigmaF must compete with sigmaA, the housekeeping
sigma factor in the predivisional cell, for binding to core RNA polymerase (E).
To estimate the relative affinity of E for sigmaA and sigmaF, we made separate
mixtures of E with each of the two sigma factors, allowed reconstitution of the
holoenzyme, and measured the concentration of free E remaining in each mixture.
The affinity of E for sigmaF was found to be about 25-fold lower than that for
sigmaA. We used quantitative Western blotting to estimate the concentrations of
E, sigmaA, and sigmaF in sporulating cells. The cellular concentrations of E and
sigmaA were both about 7.5 microM, and neither changed significantly during the
first 3 h of sporulation. The concentration of sigmaF was extremely low at the
beginning of sporulation, but it rose rapidly to a peak after about 2 h. At its
peak, the concentration of sigmaF was some twofold higher than that of sigmaA.
This difference in concentration cannot adequately account for the replacement of
sigmaA holoenzyme by sigmaF holoenzyme in the prespore, and it seems that some
further mechanism-perhaps the synthesis or activation of an anti-sigmaA factor
must be responsible for this replacement.
PMID- 10197995
TI - The steady-state internal redox state (NADH/NAD) reflects the external redox
state and is correlated with catabolic adaptation in Escherichia coli.
AB - Escherichia coli MC4100 was grown in anaerobic glucose-limited chemostat
cultures, either in the presence of an electron acceptor (fumarate, nitrate, or
oxygen) or fully fermentatively. The steady-state NADH/NAD ratio depended on the
nature of the electron acceptor. Anaerobically, the ratio was highest, and it
decreased progressively with increasing midpoint potential of the electron
acceptor. Similarly, decreasing the dissolved oxygen tension resulted in an
increased NADH/NAD ratio. As pyruvate catabolism is a major switch point between
fermentative and respiratory behavior, the fluxes through the different pyruvate
consuming enzymes were calculated. Although pyruvate formate lyase (PFL) is
inactivated by oxygen, it was inferred that the in vivo activity of the enzyme
occurred at low dissolved oxygen tensions (DOT = 1%). A simultaneous flux from
pyruvate through both PFL and the pyruvate dehydrogenase complex (PDHc) was
observed. In anaerobic cultures with fumarate or nitrate as an electron acceptor,
a significant flux through the PDHc was calculated on the basis of the redox
balance, the measured products, and the known biochemistry. This result calls
into question the common assumption that the complex cannot be active under these
conditions. In vitro activity measurements of PDHc showed that the cellular
content of the enzyme varied with the internal redox state and revealed an
activity for dissolved oxygen tension of below 1%. Whereas Western blots showed
that the E3 subunit of PDHc (dihydrolipoamide dehydrogenase) did not vary to a
large extent under the conditions tested, the E2 subunit (dihydrolipoamide
acetyltransferase) amount followed the trend that was found for the in vitro PDHc
activity. From this it is concluded that regulation of the PDHc is exerted at the
E1/E2 operon (aceEF). We propose that the external redox state (measured as the
midpoint potentials of those terminal acceptors with which the cell has
sufficient capacity to react) is reflected by the internal redox state. The
latter may subsequently govern both the expression and the activity of the two
pyruvate-catabolizing enzymes.
PMID- 10197996
TI - Genetic diversity in the protective antigen gene of Bacillus anthracis.
AB - Bacillus anthracis is a gram-positive spore-forming bacterium that causes the
disease anthrax. The anthrax toxin contains three components, including the
protective antigen (PA), which binds to eucaryotic cell surface receptors and
mediates the transport of toxins into the cell. In this study, the entire 2,294
nucleotide protective antigen gene (pag) was sequenced from 26 of the most
diverse B. anthracis strains to identify potential variation in the toxin and to
further our understanding of B. anthracis evolution. Five point mutations, three
synonymous and two missense, were identified. These differences correspond to six
different haploid types, which translate into three different amino acid
sequences. The two amino acid changes were shown to be located in an area near a
highly antigenic region critical to lethal factor binding. Nested primers were
used to amplify and sequence this same region of pag from necropsy samples taken
from victims of the 1979 Sverdlovsk incident. This investigation uncovered five
different alleles among the strains present in the tissues, including two not
seen in the 26-sample survey. One of these two alleles included a novel missense
mutation, again located just adjacent to the highly antigenic region.
Phylogenetic (cladistic) analysis of the pag corresponded with previous strain
grouping based on chromosomal variation, suggesting that plasmid evolution in B.
anthracis has occurred with little or no horizontal transfer between the
different strains.
PMID- 10197997
TI - Regulated expression of the Streptococcus mutans dlt genes correlates with
intracellular polysaccharide accumulation.
AB - Intracellular polysaccharides (IPS) are glycogen-like storage polymers which
contribute significantly to Streptococcus mutans-induced cariogenesis. We
previously identified and cloned a locus from the S. mutans chromosome which is
required for the accumulation of IPS. Sequencing of this locus revealed at least
four contiguous open reading frames, all of which are preceded by a common
promoter region and are transcribed in the same direction. Analysis of the amino
acid sequence deduced from the first of these open reading frames (ORF1) revealed
domains which are highly conserved among D-alanine-activating enzymes (DltA) in
Lactobacillus rhamnosus (formerly Lactobacillus casei) and Bacillus subtilis. The
deduced amino acid sequences derived from ORF2, -3, and -4 also exhibit extensive
similarity to DltB, -C, and -D, respectively, in these microorganisms. However,
Southern hybridization experiments indicate that this operon maps to a locus on
the S. mutans chromosome which is separate from the glgP, glgA, and glgD genes,
whose products are known mediators of bacterial IPS accumulation. We therefore
assigned a new dlt designation to the locus which we had formerly called glg. We
maintain that the dlt genes are involved in S. mutans IPS accumulation, however,
since they complement a mutation in trans which otherwise renders S. mutans IPS
deficient. In this study, we found that expression of the S. mutans dlt genes is
growth phase dependent and is modulated by carbohydrates internalized via the
phosphoenolpyruvate phosphotransferase system (PTS). We demonstrated that the S.
mutans dlt genes are expressed constitutively when non-PTS sugars are provided as
the sole source of carbohydrate. Consistent with a role for the PTS in dlt
expression is a similar constitutive expression of the dlt genes in an S. mutans
PTS mutant grown in a chemically defined medium supplemented with glucose. In
summary, these findings support a novel role for the dlt gene products in S.
mutans IPS accumulation and suggest that dlt expression in this oral pathogen is
subject to complex mechanisms of control imposed by growth phase, dietary
carbohydrate, and other factors present in the plaque environment.
PMID- 10197998
TI - Expression of a germination-specific amidase, SleB, of Bacilli in the forespore
compartment of sporulating cells and its localization on the exterior side of the
cortex in dormant spores.
AB - A germination-specific amidase of bacilli is a major spore-lytic enzyme that is
synthesized with a putative signal sequence and hydrolyses spore cortex in situ.
The sleB gene encoding this amidase in Bacillus subtilis and Bacillus cereus was
expressed in the forespore compartment of sporulating cells under the control of
sigmaG, as shown by Northern blot and primer extension analyses. The forespore
specific expression of B. subtilis sleB was further indicated by the forespore
specific accumulation of a SleB-green fluorescent protein fusion protein from
which a putative secretion signal of SleB was deleted. Immunoelectron microscopy
with anti-SleB antiserum and a colloidal gold-immunoglobulin G complex showed
that the enzymes from both Bacillus species are located just inside the spore
coat layer in the dormant spore, and in the dormant spore, the amidases appear
exist in a mature form lacking a signal sequence. These results indicate that
SleB is translocated across the forespore's inner membrane by a secretion signal
peptide and is deposited in cortex layer synthesized between the forespore inner
and outer membranes. The peripheral location of the spore-lytic enzymes in the
dormant spore suggests that spore germination is initiated at the exterior of the
cortex.
PMID- 10197999
TI - Inducing effect of diamines on transcription of the cephamycin C genes from the
lat and pcbAB promoters in Nocardia lactamdurans.
AB - The diamines putrescine, cadaverine, and diaminopropane stimulate cephamycin
biosynthesis in Nocardia lactamdurans, in shake flasks and fermentors, without
altering cell growth. Intracellular levels of the P7 protein (a component of the
methoxylation system involved in cephamycin biosynthesis) were increased by
diaminopropane, as shown by immunoblotting studies. Lysine-6-aminotransferase and
piperideine-6-carboxylate dehydrogenase activities involved in biosynthesis of
the alpha-aminoadipic acid precursor were also greatly stimulated. The diamine
stimulatory effect is exerted at the transcriptional level, as shown by low
resolution S1 protection studies. The transcript corresponding to the pcbAB gene
and to a lesser extent also the lat transcript were significantly increased in
diaminopropane-supplemented cultures, whereas transcription from the cefD
promoter was not affected. Coupling of the lat and pcbAB promoters to the
reporter xylE gene showed that expression from the lat and pcbAB promoters was
increased by addition of diaminopropane in Streptomyces lividans. Intracellular
accumulation of diamines in Nocardia may be a signal to trigger antibiotic
production.
PMID- 10198000
TI - Transcriptional organization of the czc heavy-metal homeostasis determinant from
Alcaligenes eutrophus.
AB - The Czc system of Alcaligenes eutrophus mediates resistance to cobalt, zinc, and
cadmium through ion efflux catalyzed by the CzcCB2A cation-proton antiporter. DNA
sequencing of the region upstream of the czcNICBADRS determinant located on
megaplasmid pMOL30 revealed the 5' end of czcN and a gene for a MgtC-like protein
which is transcribed in the orientation opposite that of czc. Additional open
reading frames upstream of czc had no homologs in the current databases. Using
oligonucleotide-probed Northern blotting experiments, a 500-nucleotide czcN
message and a 400-nucleotide czcI message were found, and the presence of 6, 200
nucleotide czcCBA message (D. Van der Lelie et al., Mol. Microbiol. 23:493-503,
1997) was confirmed. Induction of czcN, czcI, czcCBA, and czcDRS followed a
similar pattern: transcription was induced best by 300 microM zinc, less by 300
microM cobalt, and only slightly by 300 microM cadmium. Reverse transcription-PCR
gave evidence for additional continuous transcription from czcN to czcC and from
czcD to czcS, but not between czcA and czcD nor between czcS and a 131-amino-acid
open reading frame following czcS. The CzcR putative response regulator was
purified and shown to bind in the 5' region of czcN. A reporter strain carrying a
czcNIC-lacZ-czcBADRS determinant on plasmid pMOL30 was constructed, as were
DeltaczcR and DeltaczcS mutants of this strain and of AE128(pMOL30) wild type.
Experiments on (i) growth of these strains in liquid culture containing 5 mM
Zn2+, (ii) induction of the beta-galactosidase in the reporter strains by zinc,
cobalt, and cadmium, and (iii) cDNA analysis of czcCBA mRNA synthesis under
inducing and noninducing conditions showed that the CzcRS two-component
regulatory system is involved in Czc regulation.
PMID- 10198001
TI - mrp, a multigene, multifunctional locus in Bacillus subtilis with roles in
resistance to cholate and to Na+ and in pH homeostasis.
AB - A 5.9-kb region of the Bacillus subtilis chromosome is transcribed as a single
transcript that is predicted to encode seven membrane-spanning proteins.
Homologues of the first gene of this operon, for which the designation mrp
(multiple resistance and pH adaptation) is proposed here, have been suggested to
encode an Na+/H+ antiporter or a K+/H+ antiporter. In the present studies of the
B. subtilis mrp operon, both polar and nonpolar mutations in mrpA were generated.
Growth of these mutants was completely inhibited by concentrations of added Na+
as low as 0.3 M at pH 7.0 and 0.03 M at pH 8.3; there was no comparable
inhibition by added K+. A null mutant that was constructed by full replacement of
the mrp operon was even more Na+ sensitive. A double mutant with mutations in
both mrpA and the multifunctional antiporter-encoding tetA(L) gene was no more
sensitive than the mrpA mutants to Na+, consistent with a major role for mrpA in
Na+ resistance. Expression of mrpA from an inducible promoter, upon insertion
into the amyE locus, restored significant Na+ resistance in both the polar and
nonpolar mrpA mutants but did not restore resistance in the null mutant. The mrpA
disruption also resulted in an impairment of cytoplasmic pH regulation upon a
sudden shift in external pH from 7.5 to 8.5 in the presence of Na+ and, to some
extent, K+ in the range from 10 to 25 mM. By contrast, the mrpA tetA(L) double
mutant, like the tetA(L) single mutant, completely lost its capacity for both Na+
and K+-dependent cytoplasmic pH regulation upon this kind of shift at cation
concentrations ranging from 10 to 100 mM; thus, tetA(L) has a more pronounced
involvement than mrpA in pH regulation. Measurements of Na+ efflux from the wild
type strain, the nonpolar mrpA mutant, and the complemented mutant indicated that
inducible expression of mrpA increased the rate of protonophore- and cyanide
sensitive Na+ efflux over that in the wild-type in cells preloaded with 5 mM Na+.
The mrpA and null mutants showed no such efflux in that concentration range. This
is consistent with MrpA encoding a secondary, proton motive force-energized
Na+/H+ antiporter. Studies of a polar mutant that leads to loss of mrpFG and its
complementation in trans by mrpF or mrpFG support a role for MrpF as an efflux
system for Na+ and cholate. Part of the Na+ efflux capacity of the whole mrp
operon products is attributable to mrpF. Neither mrpF nor mrpFG expression in
trans enhanced the cholate or Na+ resistance of the null mutant. Thus, one or
more other mrp gene products must be present, but not at stoichiometric levels,
for stability, assembly, or function of both MrpF and MrpA expressed in trans.
Also, phenotypic differences among the mrp mutants suggest that functions in
addition to Na+ and cholate resistance and pH homeostasis will be found among the
remaining mrp genes.
PMID- 10198002
TI - Utilization of electrically reduced neutral red by Actinobacillus succinogenes:
physiological function of neutral red in membrane-driven fumarate reduction and
energy conservation.
AB - Neutral red (NR) functioned as an electronophore or electron channel enabling
either cells or membranes purified from Actinobacillus succinogenes to drive
electron transfer and proton translocation by coupling fumarate reduction to
succinate production. Electrically reduced NR, unlike methyl or benzyl viologen,
bound to cell membranes, was not toxic, and chemically reduced NAD. The cell
membrane of A. succinogenes contained high levels of benzyl viologen-linked
hydrogenase (12.2 U), fumarate reductase (13.1 U), and diaphorase (109.7 U)
activities. Fumarate reductase (24.5 U) displayed the highest activity with NR as
the electron carrier, whereas hydrogenase (1.1 U) and diaphorase (0.8 U) did not.
Proton translocation by whole cells was dependent on either electrically reduced
NR or H2 as the electron donor and on the fumarate concentration. During the
growth of Actinobacillus on glucose plus electrically reduced NR in an
electrochemical bioreactor system versus on glucose alone, electrically reduced
NR enhanced glucose consumption, growth, and succinate production by about 20%
while it decreased acetate production by about 50%. The rate of fumarate
reduction to succinate by purified membranes was twofold higher with electrically
reduced NR than with hydrogen as the electron donor. The addition of 2-(n-heptyl)
4-hydroxyquinoline N-oxide to whole cells or purified membranes inhibited
succinate production from H2 plus fumarate but not from electrically reduced NR
plus fumarate. Thus, NR appears to replace the function of menaquinone in the
fumarate reductase complex, and it enables A. succinogenes to utilize electricity
as a significant source of metabolic reducing power.
PMID- 10198004
TI - Structural and functional significance of the FGL sequence of the periplasmic
chaperone Caf1M of Yersinia pestis.
AB - The periplasmic molecular chaperone Caf1M of Yersinia pestis is a typical
representative of a subfamily of specific chaperones involved in assembly of
surface adhesins with a very simple structure. One characteristic feature of this
Caf1M-like subfamily is possession of an extended, variable sequence (termed FGL)
between the F1 and subunit binding G1 beta-strands. In contrast, FGS subfamily
members, characterized by PapD, have a short F1-G1 loop and are involved in
assembly of complex pili. To elucidate the structural and functional significance
of the FGL sequence, a mutant Caf1M molecule (dCaf1M), in which the 27 amino acid
residues between the F1 and G1 beta-strands had been deleted, was constructed.
Expression of the mutated caf1M in Escherichia coli resulted in accumulation of
high levels of dCaf1M. The far-UV circular dichroism spectra of the mutant and
wild-type proteins were indistinguishable and exhibited practically the same
temperature and pH dependencies. Thus, the FGL sequence of Caf1M clearly does not
contribute significantly to the stability of the protein conformation.
Preferential cleavage of Caf1M by trypsin at Lys-119 confirmed surface exposure
of this part of the FGL sequence in the isolated chaperone and periplasmic
chaperone-subunit complex. There was no evidence of surface-localized Caf1
subunit in the presence of the Caf1A outer membrane protein and dCaf1M. In
contrast to Caf1M, dCaf1M was not able to form a stable complex with Caf1 nor
could it protect the subunit from proteolytic degradation in vivo. This
demonstration that the FGL sequence is required for stable chaperone-subunit
interaction, but not for folding of a stable chaperone, provides a sound basis
for future detailed molecular analyses of the FGL subfamily of chaperones.
PMID- 10198003
TI - kdgREcc negatively regulates genes for pectinases, cellulase, protease,
HarpinEcc, and a global RNA regulator in Erwinia carotovora subsp. carotovora.
AB - Erwinia carotovora subsp. carotovora produces extracellular pectate lyase (Pel),
polygalacturonase (Peh), cellulase (Cel), and protease (Prt). The concerted
actions of these enzymes largely determine the virulence of this plant-pathogenic
bacterium. E. carotovora subsp. carotovora also produces HarpinEcc, the elicitor
of the hypersensitive reaction. We document here that KdgREcc (Kdg, 2-keto-3
deoxygluconate; KdgR, general repressor of genes involved in pectin and
galacturonate catabolism), a homolog of the E. chrysanthemi repressor, KdgREch
and the Escherichia coli repressor, KdgREco, negatively controls not only the
pectinases, Pel and Peh, but also Cel, Prt, and HarpinEcc production in E.
carotovora subsp. carotovora. The levels of pel-1, peh-1, celV, and hrpNEcc
transcripts are markedly affected by KdgREcc. The KdgREcc- mutant is more
virulent than the KdgREcc+ parent. Thus, our data for the first time establish a
global regulatory role for KdgREcc in E. carotovora subsp. carotovora. Another
novel observation is the negative effect of KdgREcc on the transcription of rsmB
(previously aepH), which specifies an RNA regulator controlling exoenzyme and
HarpinEcc production. The levels of rsmB RNA are higher in the KdgREcc- mutant
than in the KdgREcc+ parent. Moreover, by DNase I protection assays we determined
that purified KdgREcc protected three 25-bp regions within the transcriptional
unit of rsmB. Alignment of the protected sequences revealed the 21-mer consensus
sequence of the KdgREcc-binding site as 5'-G/AA/TA/TGAAA[N6]TTTCAG/TG/TA-3'. Two
such KdgREcc-binding sites occur in rsmB DNA in a close proximity to each other
within nucleotides +79 and +139 and the third KdgREcc-binding site within
nucleotides +207 and +231. Analysis of lacZ transcriptional fusions shows that
the KdgR-binding sites negatively affect the expression of rsmB. KdgREcc also
binds the operator DNAs of pel-1 and peh-1 genes and represses expression of a
pel1-lacZ and a peh1-lacZ transcriptional fusions. We conclude that KdgREcc
affects extracellular enzyme production by two ways: (i) directly, by inhibiting
the transcription of exoenzyme genes; and (ii) indirectly, by preventing the
production of a global RNA regulator. Our findings support the idea that KdgREcc
affects transcription by promoter occlusion, i.e., preventing the initiation of
transcription, and by a roadblock mechanism, i.e., by affecting the elongation of
transcription.
PMID- 10198005
TI - The CtrA response regulator mediates temporal control of gene expression during
the Caulobacter cell cycle.
AB - In its role as a global response regulator, CtrA controls the transcription of a
diverse group of genes at different times in the Caulobacter crescentus cell
cycle. To understand the differential regulation of CtrA-controlled genes, we
compared the expression of two of these genes, the fliQ flagellar gene and the
ccrM DNA methyltransferase gene. Despite their similar promoter architecture,
these genes are transcribed at different times in the cell cycle. PfliQ is
activated earlier than PccrM. Phosphorylated CtrA (CtrA approximately P) bound to
the CtrA recognition sequence in both promoters but had a 10- to 20-fold greater
affinity for PfliQ. This difference in affinity correlates with temporal changes
in the cellular levels of CtrA. Disrupting a unique inverted repeat element in
PccrM significantly reduced promoter activity but not the timing of transcription
initiation, suggesting that the inverted repeat does not play a major role in the
temporal control of ccrM expression. Our data indicate that differences in the
affinity of CtrA approximately P for PfliQ and PccrM regulate, in part, the
temporal expression of these genes. However, the timing of fliQ transcription but
not of ccrM transcription was altered in cells expressing a stable CtrA
derivative, indicating that changes in CtrA approximately P levels alone cannot
govern the cell cycle transcription of these genes. We propose that changes in
the cellular concentration of CtrA approximately P and its interaction with
accessory proteins influence the temporal expression of fliQ, ccrM, and other key
cell cycle genes and ultimately the regulation of the cell cycle.
PMID- 10198006
TI - Azospirillum irakense produces a novel type of pectate lyase.
AB - The pelA gene from the N2-fixing plant-associated bacterium Azospirillum
irakense, encoding a pectate lyase, was isolated by heterologous expression in
Escherichia coli. Nucleotide sequence analysis of the region containing pelA
indicated an open reading frame of 1,296 bp, coding for a preprotein of 432 amino
acids with a typical amino-terminal signal peptide of 24 amino acids. N-terminal
amino acid sequencing confirmed the processing of the protein in E. coli at the
signal peptidase cleavage site predicted by nucleotide sequence analysis.
Analysis of the amino acid sequence of PelA revealed no homology to other known
pectinases, indicating that PelA belongs to a new pectate lyase family. PelA
macerates potato tuber tissue, has an alkaline pH optimum, and requires Ca2+ for
its activity. Of several divalent cations tested, none could substitute for Ca2+.
Methyl-esterified pectin (with a degree of esterification up to 93%) and
polygalacturonate can be used as substrates. Characterization of the degradation
products formed upon incubation with polygalacturonate indicated that PelA is an
endo-pectate lyase generating unsaturated digalacturonide as the major end
product. Regulation of pelA expression was studied by means of a translational
pelA-gusA fusion. Transcription of this fusion is low under all growth conditions
tested and is dependent on the growth phase. In addition, pelA expression was
found to be induced by pectin. An A. irakense pelA::Tn5 mutant still displayed
pectate lyase activity, suggesting the presence of multiple pectate lyase genes
in A. irakense.
PMID- 10198007
TI - The plasmid-encoded signal peptidase SipP can functionally replace the major
signal peptidases SipS and SipT of Bacillus subtilis.
AB - The gram-positive eubacterium Bacillus subtilis is the organism with the largest
number of paralogous type I signal peptidases (SPases) known. These are specified
both by chromosomal and plasmid-borne genes. The chromosomally encoded SPases
SipS and SipT have a major function in precursor processing, and cells depleted
of SipS and SipT stop growing and die. In this study, we show that the SPase
SipP, specified by the B. subtilis plasmid pTA1015, can functionally replace SipS
and SipT, unlike the three chromosomally encoded SPases with a minor function in
protein secretion (i.e., SipU, SipV, and SipW). Unexpectedly, SipP is not
specifically required for the processing and secretion of Orf1p, which is
specified by a gene that is cotranscribed with sipP. These two genes form a
conserved structural module of rolling-circle plasmids from B. subtilis. As
previously shown for the chromosomal sipS and sipT genes, the transcription of
plasmid-borne copies of sipP is temporally controlled, reaching maximal levels
during the post-exponential growth phase when the cells secrete proteins at high
levels. However, increased transcription of sipP starts at the end of exponential
growth, about 2 h earlier than that of sipS and sipT. These data suggest that
SipP fulfills a general role in the secretory precursor processing of pTA1015
containing cells.
PMID- 10198008
TI - Distinct affinity of binding sites for S-layer homologous domains in Clostridium
thermocellum and Bacillus anthracis cell envelopes.
AB - Binding parameters were determined for the SLH (S-layer homologous) domains from
the Clostridium thermocellum outer layer protein OlpB, from the C. thermocellum S
layer protein SlpA, and from the Bacillus anthracis S-layer proteins EA1 and Sap,
using cell walls from C. thermocellum and B. anthracis. Each SLH domain bound to
C. thermocellum and B. anthracis cell walls with a different KD, ranging between
7.1 x 10(-7) and 1.8 x 10(-8) M. Cell wall binding sites for SLH domains
displayed different binding specificities in C. thermocellum and B. anthracis.
SLH-binding sites were not detected in cell walls of Bacillus subtilis. Cell
walls of C. thermocellum lost their affinity for SLH domains after treatment with
48% hydrofluoric acid but not after treatment with formamide or dilute acid. A
soluble component, extracted from C. thermocellum cells by sodium dodecyl sulfate
treatment, bound the SLH domains from C. thermocellum but not those from B.
anthracis proteins. A corresponding component was not found in B. anthracis.
PMID- 10198009
TI - The ArgR regulatory protein, a helper to the anaerobic regulator ANR during
transcriptional activation of the arcD promoter in Pseudomonas aeruginosa.
AB - Pseudomonas aeruginosa, when deprived of oxygen, generates ATP from arginine
catabolism by enzymes of the arginine deiminase pathway, encoded by the arcDABC
operon. Under conditions of low oxygen tension, the transcriptional activator ANR
binds to a site centered 41.5 bp upstream of the arcD transcriptional start. ANR
mediated anaerobic induction was enhanced two- to threefold by extracellular
arginine. This arginine effect depended, in trans, on the transcriptional
regulator ArgR and, in cis, on an ArgR binding site centered at -73.5 bp in the
arcD promoter. Binding of purified ArgR protein to this site was demonstrated by
electrophoretic mobility shift assays and DNase I footprinting. This ArgR
recognition site contained a sequence, 5'-TGACGC-3', which deviated in only 1
base from the common sequence motif 5'-TGTCGC-3' found in other ArgR binding
sites of P. aeruginosa. Furthermore, an alignment of all known ArgR binding sites
confirmed that they consist of two directly repeated half-sites. In the absence
of ANR, arginine did not induce the arc operon, suggesting that ArgR alone does
not activate the arcD promoter. According to a model proposed, ArgR makes
physical contact with ANR and thereby facilitates initiation of arc
transcription.
PMID- 10198010
TI - The adsorption protein genes of Xanthomonas campestris filamentous phages
determining host specificity.
AB - Gene III (gIII) of phiLf, a filamentous phage specifically infecting Xanthomonas
campestris pv. campestris, was previously shown to encode a virion-associated
protein (pIII) required for phage adsorption. In this study, the transcription
start site for the gene and the N-terminal sequence of the protein were
determined, resulting in the revision of the translation initiation site from the
one previously predicted for this gene. For comparative study, the gIII of phiXv,
a filamentous phage specifically infecting X. campestris pv. vesicatoria, was
cloned and sequenced. The deduced amino acid sequences of these two pIIIs exhibit
a high degree of identity in their C-terminal halves and possess the structural
features typical of the adsorption proteins of filamentous phages: a signal
sequence in the N terminus, a long glycine-rich region near the center, and a
hydrophobic membrane anchorage domain in the C terminus. The regions between gIII
and the upstream gVIII, 128 nucleotides in both phages, are larger than those of
other filamentous phages. A hybrid phage of phiXv, consisting of the phiLf pIII
and all the other components derived from phiXv, was able to infect X. campestris
pv. campestris but not X. campestris pv. vesicatoria, indicating that gIII is the
gene specifying host specificity and demonstrating the interchangeability of the
pIIIs.
PMID- 10198011
TI - Control of nitrogen catabolite repression is not affected by the tRNAGln-CUU
mutation, which results in constitutive pseudohyphal growth of Saccharomyces
cerevisiae.
AB - Saccharomyces cerevisiae responds to nitrogen availability in several ways. (i)
The cell is able to distinguish good nitrogen sources from poor ones through a
process designated nitrogen catabolite repression (NCR). Good and poor nitrogen
sources do not demonstrably affect the cell cycle other than to influence the
cell's doubling time. (ii) Nitrogen starvation promotes the initiation of
sporulation and pseudohyphal growth. (iii) Nitrogen starvation strongly affects
the cell cycle; nitrogen-starved cells arrest in G1. A specific allele of the
SUP70/CDC65 tRNAGln gene (sup70-65) has been reported to be defective in nitrogen
signaling associated with pseudohyphal formation, sporulation, and NCR. Our data
confirm that pseudohyphal growth occurs gratuitously in sup70-65 mutants cultured
in nitrogen-rich medium at 30 degrees C. However, we find neither any defect in
NCR in the sup70-65 mutant nor any alteration in the control of YVH1 expression,
which has been previously shown to be specifically induced by nitrogen
starvation.
PMID- 10198013
TI - Cloning of fibA, encoding an immunogenic subunit of the fibril-like surface
structure of Peptostreptococcus micros.
AB - Although we are currently unaware of its biological function, the fibril-like
surface structure is a prominent characteristic of the rough (Rg) genotype of the
gram-positive periodontal pathogen Peptostreptococcus micros. The smooth (Sm)
type of this species as well as the smooth variant of the Rg type (RgSm) lack
these structures on their surface. A fibril-specific serum, as determined by
immunogold electron microscopy, was obtained through adsorption of a rabbit anti
Rg type serum with excess bacteria of the RgSm type. This serum recognized a 42
kDa protein, which was subjected to N-terminal sequencing. Both clones of a
lambdaTriplEx expression library that were selected by immunoscreening with the
fibril-specific serum contained an open reading frame, designated fibA, encoding
a 393-amino-acid protein (FibA). The 15-residue N-terminal amino acid sequence of
the 42-kDa antigen was present at positions 39 to 53 in FibA; from this we
conclude that the mature FibA protein contains 355 amino acids, resulting in a
predicted molecular mass of 41,368 Da. The putative 38-residue signal sequence of
FibA strongly resembles other gram-positive secretion signal sequences. The C
termini of FibA and two open reading frames directly upstream and downstream of
fibA exhibited significant sequence homology to the C termini of a group of
secreted and surface-located proteins of other gram-positive cocci that are all
presumably involved in anchoring of the protein to carbohydrate structures. We
conclude that FibA is a secreted and surface-located protein and as such is part
of the fibril-like structures.
PMID- 10198012
TI - Isolation of Helicobacter pylori genes that modulate urease activity.
AB - Helicobacter pylori urease, a nickel-requiring metalloenzyme, hydrolyzes urea to
NH3 and CO2. We sought to identify H. pylori genes that modulate urease activity
by constructing pHP8080, a plasmid which encodes both H. pylori urease and the
NixA nickel transporter. Escherichia coli SE5000 and DH5alpha transformed with
pHP8080 resulted in a high-level urease producer and a low-level urease producer,
respectively. An H. pylori DNA library was cotransformed into SE5000 (pHP8080)
and DH5alpha (pHP8080) and was screened for cotransformants expressing either
lowered or heightened urease activity, respectively. Among the clones carrying
urease-enhancing factors, 21 of 23 contained hp0548, a gene that potentially
encodes a DNA helicase found within the cag pathogenicity island, and hp0511, a
gene that potentially encodes a lipoprotein. Each of these genes, when subcloned,
conferred a urease-enhancing activity in E. coli (pHP8080) compared with the
vector control. Among clones carrying urease-decreasing factors, 11 of 13 clones
contained the flbA (also known as flhA) flagellar biosynthesis/regulatory gene
(hp1041), an lcrD homolog. The LcrD protein family is involved in type III
secretion and flagellar secretion in pathogenic bacteria. Almost no urease
activity was detected in E. coli (pHP8080) containing the subcloned flbA gene.
Furthermore, there was significantly reduced synthesis of the urease structural
subunits in E. coli (pHP8080) containing the flbA gene, as determined by Western
blot analysis with UreA and UreB antiserum. Thus, flagellar biosynthesis and
urease activity may be linked in H. pylori. These results suggest that H. pylori
genes may modulate urease activity.
PMID- 10198014
TI - Promoter analysis of the cap8 operon, involved in type 8 capsular polysaccharide
production in Staphylococcus aureus.
AB - The production of type 8 capsular polysaccharide (CP8) in Staphylococcus aureus
is regulated in response to a variety of environmental factors. The cap8 genes
required for the CP8 production in strain Becker are transcribed as a single
large transcript by a primary promoter located within a 0.45-kb region upstream
of the first gene of the cap8 gene cluster. In this study, we analyzed the
primary cap8 promoter region in detail. We determined the transcription
initiation site of the primary transcript by primer extension and identified the
potential promoter sequences. We found several inverted and direct repeats
upstream of the promoter. Deletion analysis and site-directed mutagenesis showed
that a 10-bp inverted repeat of one of the repeats was required for promoter
activity. We showed that the distance but not the specific sequences between the
inverted repeat and the promoter was critical to the promoter activity. However,
insertion of a DNA sequence with two or four helix turns in this intervening
region had a slight effect on promoter activity. To demonstrate the biological
significance of the 10-bp inverted repeat, we constructed a strain with a
mutation in the repeat in the S. aureus Becker chromosome and showed that the
repeat affected CP8 production mostly at the transcriptional level. By gel
mobility shift assay, we demonstrated that strain Becker produced at least one
protein capable of specific binding to the 10-bp inverted repeat, indicating that
the repeat serves as a positive regulatory protein binding site. In addition,
reporter gene fusion analysis showed that the cap8 promoter activity was
influenced by various growth media and affected most by yeast extract. Our
results suggest that yeast extract may exert its profound inhibitory effect on
cap8 gene expression through the 10-bp inverted repeat element.
PMID- 10198015
TI - Cloning and characterization of two bistructural S-layer-RTX proteins from
Campylobacter rectus.
AB - Campylobacter rectus is an important periodontal pathogen in humans. A surface
layer (S-layer) protein and a cytotoxic activity have been characterized and are
thought to be its major virulence factors. The cytotoxic activity was suggested
to be due to a pore-forming protein toxin belonging to the RTX (repeats in the
structural toxins) family. In the present work, two closely related genes, csxA
and csxB (for C. rectus S-layer and RTX protein) were cloned from C. rectus and
characterized. The Csx proteins appear to be bifunctional and possess two
structurally different domains. The N-terminal part shows similarity with S-layer
protein, especially SapA and SapB of C. fetus and Crs of C. rectus. The C
terminal part comprising most of CsxA and CsxB is a domain with 48 and 59 glycine
rich canonical nonapeptide repeats, respectively, arranged in three blocks.
Purified recombinant Csx peptides bind Ca2+. These are characteristic traits of
RTX toxin proteins. The S-layer and RTX domains of Csx are separated by a proline
rich stretch of 48 amino acids. All C. rectus isolates studied contained copies
of either the csxA or csxB gene or both; csx genes were absent from all other
Campylobacter and Helicobacter species examined. Serum of a patient with acute
gingivitis showed a strong reaction to recombinant Csx protein on immunoblots.
PMID- 10198017
TI - Saturation mutagenesis of the TATA box and upstream activator sequence in the
haloarchaeal bop gene promoter.
AB - Degenerate oligonucleotides were used to randomize 21 bp of the 53-bp minimal bop
promoter in three 7-bp segments, including the putative TATA box and the upstream
activator sequence (UAS). The mutagenized bop promoter and the wild-type
structural gene and transcriptional terminator were inserted into a shuttle
plasmid capable of replication in the halophilic archaeon Halobacterium sp.
strain S9. Active promoters were isolated by screening transformants of an orange
(Pum- bop) Halobacterium mutant for purple (Pum+ bop+) colonies on agar plates
and analyzed for bop mRNA and/or bacteriorhodopsin content. Sequence analysis
yielded the consensus sequence 5'-tyT(T/a)Ta-3', corresponding to the promoter
TATA box element 30 to 25 bp 5' of the transcription start site. A putative UAS,
5'-ACCcnactagTTnG-3', located 52 to 39 bp 5' of the transcription start site was
found to be conserved in active promoters. This study provides direct evidence
for the requirement of the TATA box and UAS for bop promoter activity.
PMID- 10198016
TI - Mitomycin resistance in Streptomyces lavendulae includes a novel drug-binding
protein-dependent export system.
AB - Sequence analysis of Streptomyces lavendulae NRRL 2564 chromosomal DNA adjacent
to the mitomycin resistance locus mrd (encoding a previously described mitomycin
binding protein [P. Sheldon, D. A. Johnson, P. R. August, H.-W. Liu, and D. H.
Sherman, J. Bacteriol. 179:1796-1804, 1997]) revealed a putative mitomycin C (MC)
transport gene (mct) encoding a hydrophobic polypeptide that has significant
amino acid sequence similarity with several actinomycete antibiotic export
proteins. Disruption of mct by insertional inactivation resulted in an S.
lavendulae mutant strain that was considerably more sensitive to MC. Expression
of mct in Escherichia coli conferred a fivefold increase in cellular resistance
to MC, led to the synthesis of a membrane-associated protein, and correlated with
reduced intracellular accumulation of the drug. Coexpression of mct and mrd in E.
coli resulted in a 150-fold increase in resistance, as well as reduced
intracellular accumulation of MC. Taken together, these data provide evidence
that MRD and Mct function as components of a novel drug export system specific to
the mitomycins.
PMID- 10198018
TI - A region near the C-terminal end of Escherichia coli DNA helicase II is required
for single-stranded DNA binding.
AB - The role of the C terminus of Escherichia coli DNA helicase II (UvrD), a region
outside the conserved helicase motifs, was investigated by using three mutants:
UvrDDelta107C (deletion of the last 107 C-terminal amino acids), UvrDDelta102C,
and UvrDDelta40C. This region, which lacks sequence similarity with other
helicases, may function to tailor UvrD for its specific in vivo roles. Genetic
complementation assays demonstrated that mutant proteins UvrDDelta107C and
UvrDDelta102C failed to substitute for the wild-type protein in methyl-directed
mismatch repair and nucleotide excision repair. UvrDDelta40C protein fully
complemented the loss of helicase II in both repair pathways. UvrDDelta102C and
UvrDDelta40C were purified to apparent homogeneity and characterized
biochemically. UvrDDelta102C was unable to bind single-stranded DNA and exhibited
a greatly reduced single-stranded DNA-stimulated ATPase activity in comparison to
the wild-type protein (kcat = 0.01% of the wild-type level). UvrDDelta40C was
slightly defective for DNA binding and was essentially indistinguishable from
wild-type UvrD when single-stranded DNA-stimulated ATP hydrolysis and helicase
activities were measured. These results suggest a role for a region near the C
terminus of helicase II in binding to single-stranded DNA.
PMID- 10198019
TI - The extracellular domain of the Saccharomyces cerevisiae Sln1p membrane
osmolarity sensor is necessary for kinase activity.
AB - The function of the extracellular domain (ECD) of Sln1p, a plasma membrane two
transmembrane domain (TMD) sensor of the high-osmolarity glycerol (HOG) response
pathway, has been studied in the yeast Saccharomyces cerevisiae. Truncations of
SLN1 that retain an intact kinase domain are capable of complementing the
lethality of an sln1Delta strain. By observing levels of Hog1p phosphorylation as
well as the phosphorylation state of Sln1p, the kinase activities of various SLN1
constructions were determined. In derivatives that do not contain the first TMD,
Sln1p activity was no longer dependent on medium osmolarity but appeared to be
constitutively active even under conditions of high osmolarity. Removal of the
first TMD (DeltaTMD1 construct) gave a protein that was strongly phosphorylated
whereas Hog1p was largely dephosphorylated, as expected if the active form of
Sln1p is phosphorylated. When both TMDs as well as the ECD were deleted, so that
the kinase domain is cytosolic, Sln1p was not phosphorylated whereas Hog1p became
constitutively hyperphosphorylated. Surprisingly, this hyperactivity of the HOG
mitogen-activated protein kinase signaling pathway was not sufficient to result
in cell lethality. When the ECD of the DeltaTMD1 construct was replaced with a
leucine zipper motif, Sln1p was hyperactive, so that Hog1p became mostly
unphosphorylated. In contrast, when the Sln1p/leucine zipper construct was
crippled by a mutation of one of the internal leucines, the Sln1 kinase was
inactive. These experiments are consistent with the hypothesis that the ECD of
Sln1p functions as a dimerization and activation domain but that osmotic
regulation of activity requires the presence of the first TMD.
PMID- 10198020
TI - Investigation of two evolutionarily unrelated halocarboxylic acid dehalogenase
gene families.
AB - Dehalogenases are key enzymes in the metabolism of halo-organic compounds. This
paper describes a systematic approach to the isolation and molecular analysis of
two families of bacterial alpha-halocarboxylic acid (alphaHA) dehalogenase genes,
called group I and group II deh genes. The two families are evolutionarily
unrelated and together represent almost all of the alphaHA deh genes described to
date. We report the design and evaluation of degenerate PCR primer pairs for the
separate amplification and isolation of group I and II deh genes. Amino acid
sequences derived from 10 of 11 group I deh partial gene products of new and
previously reported bacterial isolates showed conservation of five residues
previously identified as essential for activity. The exception, DehD from a
Rhizobium sp., had only two of these five residues. Group II deh gene sequences
were amplified from 54 newly isolated strains, and seven of these sequences were
cloned and fully characterized. Group II dehalogenases were stereoselective,
dechlorinating L- but not D-2-chloropropionic acid, and derived amino acid
sequences for all of the genes except dehII degrees P11 showed conservation of
previously identified essential residues. Molecular analysis of the two deh
families highlighted four subdivisions in each, which were supported by high
bootstrap values in phylogenetic trees and by enzyme structure-function
considerations. Group I deh genes included two putative cryptic or silent genes,
dehI degrees PP3 and dehI degrees 17a, produced by different organisms. Group II
deh genes included two cryptic genes and an active gene, dehIIPP3, that can be
switched off and on. All alphaHA-degrading bacteria so far described were
Proteobacteria, a result that may be explained by limitations either in the host
range for deh genes or in isolation methods.
PMID- 10198021
TI - Accessory DNA in the genomes of representatives of the Escherichia coli reference
collection.
AB - Different strains of the Escherichia coli reference collection (ECOR) differ
widely in chromosomal size. To analyze the nature of the differential gene pool
carried by different strains, we have followed an approach in which random
amplified polymorphic DNA (RAPD) was used to generate several PCR fragments.
Those present in some but not all the strains were screened by hybridization to
assess their distribution throughout the ECOR collection. Thirteen fragments with
various degrees of occurrence were sequenced. Three of them corresponded to RAPD
markers of widespread distribution. Of these, two were housekeeping genes shown
by hybridization to be present in all the E. coli strains and in Salmonella
enterica LT2; the third fragment contained a paralogous copy of dnaK with
widespread, but not global, distribution. The other 10 RAPD markers were found in
only a few strains. However, hybridization results demonstrated that four of them
were actually present in a large selection of the ECOR collection (between 42 and
97% of the strains); three of these fragments contained open reading frames
associated with phages or plasmids known in E. coli K-12. The remaining six
fragments were present in only between one and four strains; of these, four
fragments showed no similarity to any sequence in the databases, and the other
two had low but significant similarity to a protein involved in the Klebsiella
capsule synthesis and to RNA helicases of archaeal genomes, respectively. Their
percent GC, dinucleotide content, and codon adaptation index suggested an
exogenous origin by horizontal transfer. These results can be interpreted as
reflecting the presence of a large pool of strain-specific genes, whose origin
could be outside the species boundaries.
PMID- 10198022
TI - Clathrin and two components of the COPII complex, Sec23p and Sec24p, could be
involved in endocytosis of the Saccharomyces cerevisiae maltose transporter.
AB - The Saccharomyces cerevisiae maltose transporter is a 12-transmembrane segment
protein that under certain physiological conditions is degraded in the vacuole
after internalization by endocytosis. Previous studies showed that endocytosis of
this protein is dependent on the actin network, is independent of microtubules,
and requires the binding of ubiquitin. In this work, we attempted to determine
which coat proteins are involved in this endocytosis. Using mutants defective in
the heavy chain of clathrin and in several subunits of the COPI and the COPII
complexes, we found that clathrin, as well as two cytosolic subunits of COPII,
Sec23p and Sec24p, could be involved in internalization of the yeast maltose
transporter. The results also indicate that endocytosis of the maltose
transporter and of the alpha-factor receptor could have different requirements.
PMID- 10198023
TI - Bacteroides fragilis transfer factor Tn5520: the smallest bacterial mobilizable
transposon containing single integrase and mobilization genes that function in
Escherichia coli.
AB - Many bacterial genera, including Bacteroides spp., harbor mobilizable
transposons, a class of transfer factors that carry genes for conjugal DNA
transfer and, in some cases, antibiotic resistance. Mobilizable transposons are
capable of inserting into and mobilizing other, nontransferable plasmids and are
implicated in the dissemination of antibiotic resistance. This paper presents the
isolation and characterization of Tn5520, a new mobilizable transposon from
Bacteroides fragilis LV23. At 4,692 bp, it is the smallest mobilizable transposon
reported from any bacterial genus. Tn5520 was captured from B. fragilis LV23 by
using the transfer-deficient shuttle vector pGAT400DeltaBglII. The termini of
Tn5520 contain a 22-bp imperfect inverted repeat, and transposition does not
result in a target site repeat. Tn5520 also demonstrates insertion site sequence
preferences characterized by A-T-rich nucleotide sequences. Tn5520 has been
sequenced in its entirety, and two large open reading frames whose predicted
protein products exhibit strong sequence similarity to recombinase-integrase
enzymes and mobilization proteins, respectively, have been identified. The
transfer, mobilization, and transposition properties of Tn5520 have been studied,
revealing that Tn5520 mobilizes plasmids in both B. fragilis and Escherichia coli
at high frequency and also transposes in E. coli.
PMID- 10198024
TI - Genetic analysis of the mobilization and leading regions of the IncN plasmids
pKM101 and pCU1.
AB - The conjugative IncN plasmids pKM101 and pCU1 have previously been shown to
contain identical oriT sequences as well as conserved restriction endonuclease
cleavage patterns within their tra regions. Complementation analysis and sequence
data presented here indicate that these two plasmids encode essentially identical
conjugal DNA-processing proteins. This region contains three genes, traI, traJ,
and traK, transcribed in the same orientation from a promoter that probably lies
within or near the conjugal transfer origin (oriT). Three corresponding proteins
were visualized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and
complementation analysis confirmed that this region contains three tra
complementation groups. All three proteins resemble proteins of the IncW plasmid
R388 and other plasmids thought to have roles in processing of plasmid DNA during
conjugation. The hydropathy profile of TraJ suggests a transmembrane topology
similar to that of several homologous proteins. Both traK and traI were required
for efficient interplasmid site-specific recombination at oriT, while traJ was
not required. The leading region of pKM101 contains three genes (stbA, stbB, and
stbC), null mutations in which cause elevated levels of plasmid instability.
Plasmid instability was observed only in hosts that are proficient in
interplasmid recombination, suggesting that this recombination can potentially
lead to plasmid loss and that Stb proteins somehow overcome this, possibly via
site-specific multimer resolution.
PMID- 10198025
TI - Analysis of an autoregulatory loop controlling ToxT, cholera toxin, and toxin
coregulated pilus production in Vibrio cholerae.
AB - Coordinate expression of many virulence genes in the human pathogen Vibrio
cholerae is controlled by the ToxR, TcpP, and ToxT proteins. These proteins
function in a regulatory cascade in which ToxR and TcpP, two inner membrane
proteins, are required to activate toxT and ToxT is the direct activator of
virulence gene expression. ToxT-activated genes include those whose products are
required for the biogenesis of cholera toxin (CTX) and the toxin-coregulated
pilus, the major subunit of which is TcpA. This work examined control of toxT
transcription. We tested a model whereby activation of toxT by ToxR and TcpP is
required to prime an autoregulatory loop in which ToxT-dependent transcription of
the tcpA promoter reads through a proposed terminator between the tcpF and toxT
genes to result in continued ToxT production. Primer extension analysis of RNA
from wild-type classical strain O395 showed that there are two products encoding
toxT, one of which is longer than the other by 105 bp. Deletion of the toxT
promoter (toxTDeltapro) resulted in the abolishment of toxT transcription, as
predicted. Deletion of the tcpA promoter (tcpADeltapro) had no effect on
subsequent detection of the smaller toxT primer extension product, but the larger
toxT product was not detected, indicating that this product may be the result of
transcription from the tcpA promoter and not of initiation directly upstream of
toxT. Neither mutant strain produced detectable TcpA, but the CTX levels of the
strains were different. The toxTDeltapro strain produced little detectable CTX,
while the tcpADeltapro strain produced CTX levels intermediate between those of
the wild-type and toxTDeltapro strains. Dependence of toxT transcription on TcpP
and TcpH was confirmed by analyzing RNAs from strains carrying deletions in the
genes encoding these regulators. The tcpP defect resulted in undetectable toxT
transcription, whereas the tcpH mutation led to a diminishing of toxT RNA but not
complete abolishment. Taken together, these results suggest that toxT
transcription is dependent on two different promoters; one is directly upstream
and is activated in part by TcpP and TcpH, and the other is much further upstream
and is activated by ToxT.
PMID- 10198026
TI - Gliding mutants of Myxococcus xanthus with high reversal frequencies and small
displacements.
AB - Myxococcus xanthus cells move on a solid surface by gliding motility. Several
genes required for gliding motility have been identified, including those of the
A- and S-motility systems as well as the mgl and frz genes. However, the cellular
defects in gliding movement in many of these mutants were unknown. We conducted
quantitative, high-resolution single-cell motility assays and found that mutants
defective in mglAB or in cglB, an A-motility gene, reversed the direction of
gliding at frequencies which were more than 1 order of magnitude higher than that
of wild type cells (2.9 min-1 for DeltamglAB mutants and 2.7 min-1 for cglB
mutants, compared to 0.17 min-1 for wild-type cells). The average gliding speed
of DeltamglAB mutant cells was 40% of that of wild-type cells (on average 1.9
micrometers/min for DeltamglAB mutants, compared to 4.4 micrometers/min for wild
type cells). The mglA-dependent reversals and gliding speeds were dependent on
the level of intracellular MglA protein: mglB mutant cells, which contain only 15
to 20% of the wild-type level of MglA protein, glided with an average reversal
frequency of about 1.8 min-1 and an average speed of 2.6 micrometers/min. These
values range between those exhibited by wild-type cells and by DeltamglAB mutant
cells. Epistasis analysis of frz mutants, which are defective in aggregation and
in single-cell reversals, showed that a frzD mutation, but not a frzE mutation,
partially suppressed the mglA phenotype. In contrast to mgl mutants, cglB mutant
cells were able to move with wild-type speeds only when in close proximity to
each other. However, under those conditions, these mutant cells were found to
glide less often with those speeds. By analyzing double mutants, the high
reversing movements and gliding speeds of cglB cells were found to be strictly
dependent on type IV pili, encoded by S-motility genes, whereas the high-reversal
pattern of mglAB cells was only partially reduced by a pilR mutation. These
results suggest that the MglA protein is required for both control of reversal
frequency and gliding speed and that in the absence of A motility, type IV pilus
dependent cell movement includes reversals at high frequency. Furthermore, mglAB
mutants behave as if they were severely defective in A motility but only
partially defective in S motility.
PMID- 10198027
TI - cis-Acting elements responsible for low-temperature-inducible expression of the
gene coding for the thermolabile isocitrate dehydrogenase isozyme of a
psychrophilic bacterium, Vibrio sp. strain ABE-1.
AB - Transcriptional control of the low-temperature-inducible icdII gene, encoding the
thermolabile isocitrate dehydrogenase of a psychrophilic bacterium, Vibrio sp.
strain ABE-1, was found to be mediated in part by a transcriptional silencer
locating at nucleotide positions -560 to -526 upstream from the transcription
start site of icdII. Deletion of the silencer resulted in a 20-fold-increased
level of expression of the gene at low temperature (15 degrees C) but not at high
temperature (37 degrees C). In addition, a CCAAT sequence located 2 bases
upstream of the -35 region was found to be essential for the low-temperature
inducible expression of the gene. By deletion of this sequence, low-temperature
dependent expression of the gene was completely abolished. The ability of the
icdII promoter to control the expression of other genes was confirmed by using a
fusion gene containing the icdII promoter region and the promoterless icdI open
reading frame, which encodes the non-cold-inducible isocitrate dehydrogenase
isozyme of Vibrio sp. strain ABE-1. Escherichia coli transformants harboring
icdII acquired an ability to grow rapidly at low temperature.
PMID- 10198028
TI - Acarbose, a pseudooligosaccharide, is transported but not metabolized by the
maltose-maltodextrin system of Escherichia coli.
AB - The pseudooligosaccharide acarbose is a potent inhibitor of amylases,
glucosidases, and cyclodextrin glycosyltransferase and is clinically used for the
treatment of so-called type II or insulin-independent diabetes. The compound
consists of an unsaturated aminocyclitol, a deoxyhexose, and a maltose. The
unsaturated aminocyclitol moiety (also called valienamine) is primarily
responsible for the inhibition of glucosidases. Due to its structural similarity
to maltotetraose, we have investigated whether acarbose is recognized as a
substrate by the maltose/maltodextrin system of Escherichia coli. Acarbose at
millimolar concentrations specifically affected the growth of E. coli K-12 on
maltose as the sole source of carbon and energy. Uptake of radiolabeled maltose
was competitively inhibited by acarbose, with a Ki of 1.1 microM. Maltose-grown
cells transported radiolabeled acarbose, indicating that the compound is
recognized as a substrate. Studying the interaction of acarbose with purified
maltoporin in black lipid membranes revealed that the kinetics of acarbose
binding to LamB is asymmetric. The on-rate of acarbose is approximately 30 times
lower when the molecule enters the pore from the extracellular side than when it
enters from the periplasmic side. Acarbose could not be utilized as a carbon
source since the compound alone was not a substrate of amylomaltase (MalQ) and
was only poorly attacked by maltodextrin glucosidase (MalZ).
PMID- 10198029
TI - The lactate-proton symport of Saccharomyces cerevisiae is encoded by JEN1.
AB - A mutant of Saccharomyces cerevisiae deficient in the lactate-proton symport was
isolated. Transformation of the mutant with a yeast genomic library allowed the
isolation of the gene JEN1 that restored lactate transport. Disruption of JEN1
abolished uptake of lactate. The results indicate that, under the experimental
conditions tested, no other monocarboxylate permease is able to efficiently
transport lactate in S. cerevisiae.
PMID- 10198030
TI - Correlation of 16S ribosomal DNA signature sequences with temperature-dependent
growth rates of mesophilic and psychrotolerant strains of the Bacillus cereus
group.
AB - Sequences of the 16S ribosomal DNA (rDNA) from psychrotolerant and mesophilic
strains of the Bacillus cereus group revealed signatures which were specific for
these two thermal groups of bacteria. Further analysis of the genomic DNA from a
wide range of food and soil isolates showed that B. cereus group strains have
between 6 and 10 copies of 16S rDNA. Moreover, a number of these environmental
strains have both rDNA operons with psychrotolerant signatures and rDNA operons
with mesophilic signatures. The ability of these isolates to grow at low
temperatures correlates with the prevalence of rDNA operons with psychrotolerant
signatures, indicating specific nucleotides within the 16S rRNA to play a role in
psychrotolerance.
PMID- 10198031
TI - Assembly requirements and role of CotH during spore coat formation in Bacillus
subtilis.
AB - We report Western blot data showing that the 42.8-kDa product of the previously
characterized cotH locus (8) is a structural component of the Bacillus subtilis
spore coat. We show that the assembly of CotH requires both CotE and GerE. In
agreement with these observations, the ultrastructural analysis of purified
spores suggests that CotH is needed for proper formation of both inner and outer
layers of the coat.
PMID- 10198032
TI - Differential regulation of two divergent Sinorhizobium meliloti genes for HPII
like catalases during free-living growth and protective role of both catalases
during symbiosis.
AB - Two catalases, KatA and KatB, have been detected in Sinorhizobium meliloti
growing on rich medium. Here we characterize a new catalase gene encoding a third
catalase (KatC). KatC activity was detectable only at the end of the stationary
phase in S. meliloti growing in minimum medium, whereas KatA activity was found
during the exponential phase. Analysis with a katC-lacZ fusion demonstrated that
katC expression is mainly regulated at the transcription level. An increase of
catalase activity correlating with KatA induction was detected in bacteroids. A
dramatic decrease of nitrogen fixation capacity in a katA katC double mutant was
observed, suggesting that these catalases are very important for the protection
of the nitrogen fixation process.
PMID- 10198033
TI - Cyclic AMP can decrease expression of genes subject to catabolite repression in
Saccharomyces cerevisiae.
AB - External cyclic AMP (cAMP) hindered the derepression of gluconeogenic enzymes in
a pde2 mutant of Saccharomyces cerevisiae, but it did not prevent invertase
derepression. cAMP reduced nearly 20-fold the transcription driven by upstream
activation sequence (UAS1FBP1) from FBP1, encoding fructose-1,6-bisphosphatase;
it decreased 2-fold the activation of transcription by UAS2FBP1. Nuclear extracts
from cells derepressed in the presence of cAMP were impaired in the formation of
specific UASFBP1-protein complexes in band shift experiments. cAMP does not
appear to act through the repressing protein Mig1. Control of FBP1 transcription
through cAMP is redundant with other regulatory mechanisms.
PMID- 10198034
TI - In vitro synthesis of peptidoglycan precursors modified with N-acetylputrescine
by Cyanophora paradoxa cyanelle envelope membranes.
AB - The photosynthetic organelles (cyanelles) of the protist Cyanophora paradoxa are
surrounded by a peptidoglycan wall, modified through amidation with N
acetylputrescine. Cyanelle envelope membrane preparations were shown to catalyze
the lipid-linked steps of peptidoglycan biosynthesis as well as the
putrescinylation and subsequent acetylation, occurring at the stage of lipid I
and/or lipid II.
PMID- 10198035
TI - Bordetella pertussis waaA encodes a monofunctional 2-keto-3-deoxy-D-manno
octulosonic acid transferase that can complement an Escherichia coli waaA
mutation.
AB - Bordetella pertussis lipopolysaccharide (LPS) contains a single 2-keto-3-deoxy-D
manno-octulosonic acid (Kdo) residue, whereas LPS from Escherichia coli contains
at least two. Here we report that B. pertussis waaA encodes an enzyme capable of
transferring only a single Kdo during the biosynthesis of LPS and that this
activity is sufficient to complement an E. coli waaA mutation.
PMID- 10198036
TI - The type 2 capsule locus of Streptococcus pneumoniae.
AB - The type 2 capsule locus of Streptococcus pneumoniae was characterized in Avery's
strain D39, which is the parent strain of the standard transformation recipients
currently used in pneumococcal research and is largely used as a virulent strain
in studies on the pathogenesis of pneumococcal infections. The capsule locus was
sequenced by using a 21.7-kb PCR fragment from the D39 genome as a template.
Sequence data analysis showed the presence of 18 open reading frames, 17 of which
have the same direction of transcription and all of which are potentially
involved in capsule biosynthesis. It was also shown that R36A and R6, which are
unencapsulated (rough) derivatives of D39, carry a 7,504-bp deletion involving
nine capsule genes.
PMID- 10198037
TI - Azorhizobium caulinodans PII and GlnK proteins control nitrogen fixation and
ammonia assimilation.
AB - We herein report that Azorhizobium caulinodans PII and GlnK are not necessary for
glutamine synthetase (GS) adenylylation whereas both proteins are required for
complete GS deadenylylation. The disruption of both glnB and glnK resulted in a
high level of GS adenylylation under the condition of nitrogen fixation, leading
to ammonium excretion in the free-living state. PII and GlnK also controlled nif
gene expression because NifA activated nifH transcription and nitrogenase
activity was derepressed in glnB glnK double mutants, but not in wild-type
bacteria, grown in the presence of ammonia.
PMID- 10198038
TI - Sequence analysis of the four plasmid genes required to produce the circular
peptide antibiotic microcin J25.
AB - A 4.8-kb plasmid region carrying the four genes mcjABCD necessary for production
of and immunity to the cyclic peptide antibiotic microcin J25 (MccJ25) has been
sequenced. mcjA encodes the primary structure of MccJ25 as a precursor endowed
with an N-terminal extension of 37 amino acids. The products of mcjB and mcjC are
thought to be involved in microcin maturation, which implies cleavage of McjA and
head-tail linkage of the 21-residue pro-MccJ25. The predicted McjD polypeptide,
which is highly similar to several ABC exporters, was found to be required for
MccJ25 secretion, thus explaining its ability to confer immunity to MccJ25.
PMID- 10198039
TI - Localization of Escherichia coli rpoC mutations that affect RNA polymerase
assembly and activity at high temperature.
AB - We localized five rpoC (beta') mutations affecting Escherichia coli RNA
polymerase assembly. The Ts4, XH56, and R120 mutations changed beta' residues
conserved throughout eubacteria; the JE10092 mutation occurred in the
hypervariable region; rpoC1 (TsX) changed a universally conserved residue and
corresponds to yeast rpb1-1. Thus, distinct, predominantly conserved beta'
residues participate in interactions holding RNA polymerase together.
PMID- 10198040
TI - Protein interactions with the glucose transporter binding protein GLUT1CBP that
provide a link between GLUT1 and the cytoskeleton.
AB - Subcellular targeting and the activity of facilitative glucose transporters are
likely to be regulated by interactions with cellular proteins. This report
describes the identification and characterization of a protein, GLUT1 C-terminal
binding protein (GLUT1CBP), that binds via a PDZ domain to the C terminus of
GLUT1. The interaction requires the C-terminal four amino acids of GLUT1 and is
isoform specific because GLUT1CBP does not interact with the C terminus of GLUT3
or GLUT4. Most rat tissues examined contain both GLUT1CBP and GLUT1 mRNA, whereas
only small intestine lacked detectable GLUT1CBP protein. GLUT1CBP is also
expressed in primary cultures of neurons and astrocytes, as well as in Chinese
hamster ovary, 3T3-L1, Madin-Darby canine kidney, Caco-2, and pheochromocytoma-12
cell lines. GLUT1CBP is able to bind to native GLUT1 extracted from cell
membranes, self-associate, or interact with the cytoskeletal proteins myosin VI,
alpha-actinin-1, and the kinesin superfamily protein KIF-1B. The presence of a
PDZ domain places GLUT1CBP among a growing family of structural and regulatory
proteins, many of which are localized to areas of membrane specialization. This
and its ability to interact with GLUT1 and cytoskeletal proteins implicate
GLUT1CBP in cellular mechanisms for targeting GLUT1 to specific subcellular sites
either by tethering the transporter to cytoskeletal motor proteins or by
anchoring the transporter to the actin cytoskeleton.
PMID- 10198041
TI - Cdc25 inhibited in vivo and in vitro by checkpoint kinases Cds1 and Chk1.
AB - In the fission yeast Schizosaccharomyces pombe, the protein kinase Cds1 is
activated by the S-M replication checkpoint that prevents mitosis when DNA is
incompletely replicated. Cds1 is proposed to regulate Wee1 and Mik1, two tyrosine
kinases that inhibit the mitotic kinase Cdc2. Here, we present evidence from in
vivo and in vitro studies, which indicates that Cds1 also inhibits Cdc25, the
phosphatase that activates Cdc2. In an in vivo assay that measures the rate at
which Cdc25 catalyzes mitosis, Cds1 contributed to a mitotic delay imposed by the
S-M replication checkpoint. Cds1 also inhibited Cdc25-dependent activation of
Cdc2 in vitro. Chk1, a protein kinase that is required for the G2-M damage
checkpoint that prevents mitosis while DNA is being repaired, also inhibited
Cdc25 in the in vitro assay. In vitro, Cds1 and Chk1 phosphorylated Cdc25
predominantly on serine-99. The Cdc25 alanine-99 mutation partially impaired the
S-M replication and G2-M damage checkpoints in vivo. Thus, Cds1 and Chk1 seem to
act in different checkpoint responses to regulate Cdc25 by similar mechanisms.
PMID- 10198042
TI - Genetic dissection of endocytic trafficking in Drosophila using a horseradish
peroxidase-bride of sevenless chimera: hook is required for normal maturation of
multivesicular endosomes.
AB - Mutations in the hook gene alter intracellular trafficking of internalized
ligands in Drosophila. To dissect this defect in more detail, we developed a new
approach to visualize the pathway taken by the Bride of Sevenless (Boss) ligand
after its internalization into R7 cells. A chimeric protein consisting of HRP
fused to Boss (HRP-Boss) was expressed in R8 cells. This chimera was fully
functional: it rescued the boss mutant phenotype, and its trafficking was
indistinguishable from that of the wild-type Boss protein. The HRP activity of
the chimera was used to follow HRP-Boss trafficking on the ultrastructural level
through early and late endosomes in R7 cells. In both wild-type and hook mutant
eye disks, HRP-Boss was internalized into R7 cells. In wild-type tissue, Boss
accumulated in mature multivesicular bodies (MVBs) within R7 cells; such
accumulation was not observed in hook eye disks, however. Quantitative electron
microscopy revealed a loss of mature MVBs in hook mutant tissue compared with
wild type, whereas more than twice as many multilammelar late endosomes were
detected. Our genetic analysis indicates that Hook is required late in endocytic
trafficking to negatively regulate delivery from mature MVBs to multilammelar
late endosomes and lysosomes.
PMID- 10198043
TI - Specific activation of leukocyte beta2 integrins lymphocyte function-associated
antigen-1 and Mac-1 by chemokines mediated by distinct pathways via the alpha
subunit cytoplasmic domains.
AB - We show that CC chemokines induced a sustained increase in monocyte adhesion to
intercellular adhesion molecule-1 that was mediated by Mac-1 (alphaMbeta2) but
not lymphocyte function-associated antigen-1 (LFA-1; alphaLbeta2). In contrast,
staining for an activation epitope revealed a rapid and transient up-regulation
of LFA-1 activity by monocyte chemotactic protein-1 (MCP-1) in monocytes and
Jurkat CCR2 chemokine receptor transfectants or by stromal-derived factor-1alpha
in Jurkat cells. Differential kinetics for activation of Mac-1 (sustained) and
LFA-1 (transient) avidity in response to stromal-derived factor-1alpha were
confirmed by expression of alphaM or alphaL in alphaL-deficient Jurkat cells.
Moreover, expression of chimeras containing alphaL and alphaM cytoplasmic domain
exchanges indicated that alpha cytoplasmic tails conferred the specific mode of
regulation. Coexpressing alphaM or chimeras in mutant Jurkat cells with a "gain
of function" phenotype that results in constitutively active LFA-1 demonstrated
that Mac-1 was not constitutively active, whereas constitutive activity was
mediated via the alphaL cytoplasmic tail, implying the presence of distinct
signaling pathways for LFA-1 and Mac-1. Transendothelial chemotaxis of monocytes
in response to MCP-1 was dependent on LFA-1; however, Mac-1 was involved at MCP-1
concentrations stimulating its avidity, showing differential contributions of
beta2 integrins. Our data suggest that a specific regulation of beta2 integrin
avidity by chemokines may be important in leukocyte extravasation and may be
triggered by distinct activation pathways transduced via the alpha subunit
cytoplasmic domains.
PMID- 10198044
TI - Distinct domains within Vps35p mediate the retrieval of two different cargo
proteins from the yeast prevacuolar/endosomal compartment.
AB - Resident membrane proteins of the trans-Golgi network (TGN) of Saccharomyces
cerevisiae are selectively retrieved from a prevacuolar/late endosomal
compartment. Proper cycling of the carboxypeptidase Y receptor Vps10p between the
TGN and prevacuolar compartment depends on Vps35p, a hydrophilic peripheral
membrane protein. In this study we use a temperature-sensitive vps35 allele to
show that loss of Vps35p function rapidly leads to mislocalization of A-ALP, a
model TGN membrane protein, to the vacuole. Vps35p is required for the
prevacuolar compartment-to-TGN transport of both A-ALP and Vps10p. This was
demonstrated by phenotypic analysis of vps35 mutant strains expressing A-ALP
mutants lacking either the retrieval or static retention signals and by an assay
for prevacuolar compartment-to-TGN transport. A novel vps35 allele was identified
that was defective for retrieval of A-ALP but functional for retrieval of Vps10p.
Moreover, several other vps35 alleles were identified with the opposite
characteristics: they were defective for Vps10p retrieval but near normal for A
ALP localization. These data suggest a model in which distinct structural
features within Vps35p are required for associating with the cytosolic domains of
each cargo protein during the retrieval process.
PMID- 10198045
TI - Microdomain-dependent regulation of Lck and Fyn protein-tyrosine kinases in T
lymphocyte plasma membranes.
AB - Src family protein-tyrosine kinases are implicated in signaling via
glycosylphosphatidylinositol (GPI)-anchored receptors. Both kinds of molecules
reside in opposite leaflets of the same sphingolipid-enriched microdomains in the
lymphocyte plasma membrane without making direct contact. Under detergent-free
conditions, we isolated a GPI-enriched plasma membrane fraction, also containing
transmembrane proteins, selectively associated with sphingolipid microdomains.
Nonionic detergents released the transmembrane proteins, yielding core
sphingolipid microdomains, limited amounts of which could also be obtained by
detergent-free subcellular fractionation. Protein-tyrosine kinase activity in
membranes containing both GPI-anchored and transmembrane proteins was much lower
than in core sphingolipid microdomains but was strongly reactivated by nonionic
detergents. The inhibitory mechanism acting on Lck and Fyn kinases in these
membranes was independent of the protein-tyrosine phosphatase CD45 and was
characterized as a mixed, noncompetitive one. We propose that in lymphocyte
plasma membranes, Lck and Fyn kinases exhibit optimal activity when juxtaposed to
the GPI- and sphingolipid-enriched core microdomains but encounter inhibitory
conditions in surrounding membrane areas that are rich in glycerophospholipids
and contain additional transmembrane proteins.
PMID- 10198046
TI - Hypoxic regulation of vascular endothelial growth factor mRNA stability requires
the cooperation of multiple RNA elements.
AB - Vascular endothelial growth factor (VEGF) is a key regulator of developmental,
physiological, and tumor angiogenesis. Upregulation of VEGF expression by hypoxia
appears to be a critical step in the neovascularization of solid cancers. The
VEGF mRNA is intrinsically labile, but in response to hypoxia the mRNA is
stabilized. We have systematically analyzed the regions in the VEGF mRNA that are
responsible for its lability under normoxic conditions and for stabilization in
response to hypoxia. We find that the VEGF mRNA not only contains destabilizing
elements in its 3' untranslated region (3'UTR), but also contains destabilizing
elements in the 5'UTR and coding region. Each region can independently promote
mRNA degradation, and together they act additively to effect rapid degradation
under normoxic conditions. Stabilization of the mRNA in response to hypoxia is
completely dependent on the cooperation of elements in each of the 5'UTR, coding
region, and 3'UTR. Combinations of any of two of these three regions were
completely ineffective in responding to hypoxia, whereas combining all three
regions allowed recapitulation of the hypoxic stabilization seen with the
endogenous VEGF mRNA. We conclude that multiple regions in the VEGF mRNA
cooperate both to ensure the rapid degradation of the mRNA under normoxic
conditions and to allow stabilization of the mRNA in response to hypoxia. Our
findings highlight the complexity of VEGF gene expression and also reveal a
mechanism of gene regulation that could become the target for strategies of
therapeutic intervention.
PMID- 10198047
TI - Inhibition of secretion by 1,3-Cyclohexanebis(methylamine), a dibasic compound
that interferes with coatomer function.
AB - We noted previously that certain aminoglycoside antibiotics inhibit the binding
of coatomer to Golgi membranes in vitro. The inhibition is mediated in part by
two primary amino groups present at the 1 and 3 positions of the 2
deoxystreptamine moiety of the antibiotics. These two amines appear to mimic the
epsilon-amino groups present in the two lysine residues of the KKXX motif that is
known to bind coatomer. Here we report the effects of 1, 3
cyclohexanebis(methylamine) (CBM) on secretion in vivo, a compound chosen for
study because it contains primary amino groups that resemble those in 2
deoxystreptamine and it should penetrate lipid bilayers more readily than
antibiotics. CBM inhibited coatomer binding to Golgi membranes in vitro and in
vivo and inhibited secretion by intact cells. Despite depressed binding of
coatomer in vivo, the Golgi complex retained its characteristic perinuclear
location in the presence of CBM and did not fuse with the endoplasmic reticulum
(ER). Transport from the ER to the Golgi was also not blocked by CBM. These data
suggest that a full complement of coat protein I (COPI) on membranes is not
critical for maintenance of Golgi integrity or for traffic from the ER to the
Golgi but is necessary for transport through the Golgi to the plasma membrane.
PMID- 10198048
TI - High resolution detection of mechanical forces exerted by locomoting fibroblasts
on the substrate.
AB - We have developed a new approach to detect mechanical forces exerted by
locomoting fibroblasts on the substrate. Cells were cultured on elastic, collagen
coated polyacrylamide sheets embedded with 0. 2-micrometer fluorescent beads.
Forces exerted by the cell cause deformation of the substrate and displacement of
the beads. By recording the position of beads during cell locomotion and after
cell removal, we discovered that most forces were radially distributed, switching
direction in the anterior region. Deformations near the leading edge were strong,
transient, and variable in magnitude, consistent with active local contractions,
whereas those in the posterior region were weaker, more stable, and more uniform,
consistent with passive resistance. Treatment of cells with cytochalasin D or
myosin II inhibitors caused relaxation of the forces, suggesting that they are
generated primarily via actin-myosin II interactions; treatment with nocodazole
caused no immediate effect on forces. Immunofluorescence indicated that the
frontal region of strong deformation contained many vinculin plaques but no
apparent concentration of actin or myosin II filaments. Strong mechanical forces
in the anterior region, generated by locally activated myosin II and transmitted
through vinculin-rich structures, likely play a major role in cell locomotion and
in mechanical signaling with the surrounding environment.
PMID- 10198049
TI - Taxol suppresses dynamics of individual microtubules in living human tumor cells.
AB - Microtubules are intrinsically dynamic polymers, and their dynamics play a
crucial role in mitotic spindle assembly, the mitotic checkpoint, and chromosome
movement. We hypothesized that, in living cells, suppression of microtubule
dynamics is responsible for the ability of taxol to inhibit mitotic progression
and cell proliferation. Using quantitative fluorescence video microscopy, we
examined the effects of taxol (30-100 nM) on the dynamics of individual
microtubules in two living human tumor cell lines: Caov-3 ovarian adenocarcinoma
cells and A-498 kidney carcinoma cells. Taxol accumulated more in Caov-3 cells
than in A-498 cells. At equivalent intracellular taxol concentrations, dynamic
instability was inhibited similarly in the two cell lines. Microtubule shortening
rates were inhibited in Caov-3 cells and in A-498 cells by 32 and 26%, growing
rates were inhibited by 24 and 18%, and dynamicity was inhibited by 31 and 63%,
respectively. All mitotic spindles were abnormal, and many interphase cells
became multinucleate (Caov-3, 30%; A-498, 58%). Taxol blocked cell cycle progress
at the metaphase/anaphase transition and inhibited cell proliferation. The
results indicate that suppression of microtubule dynamics by taxol deleteriously
affects the ability of cancer cells to properly assemble a mitotic spindle, pass
the metaphase/anaphase checkpoint, and produce progeny.
PMID- 10198050
TI - Extraction of cholesterol with methyl-beta-cyclodextrin perturbs formation of
clathrin-coated endocytic vesicles.
AB - The importance of cholesterol for endocytosis has been investigated in HEp-2 and
other cell lines by using methyl-beta-cyclodextrin (MbetaCD) to selectively
extract cholesterol from the plasma membrane. MbetaCD treatment strongly
inhibited endocytosis of transferrin and EGF, whereas endocytosis of ricin was
less affected. The inhibition of transferrin endocytosis was completely
reversible. On removal of MbetaCD it was restored by continued incubation of the
cells even in serum-free medium. The recovery in serum-free medium was inhibited
by addition of lovastatin, which prevents cholesterol synthesis, but endocytosis
recovered when a water-soluble form of cholesterol was added together with
lovastatin. Electron microscopical studies of MbetaCD-treated HEp-2 cells
revealed that typical invaginated caveolae were no longer present. Moreover, the
invagination of clathrin-coated pits was strongly inhibited, resulting in
accumulation of shallow coated pits. Quantitative immunogold labeling showed that
transferrin receptors were concentrated in coated pits to the same degree
(approximately sevenfold) after MbetaCD treatment as in control cells. Our
results therefore indicate that although clathrin-independent (and caveolae
independent) endocytosis still operates after removal of cholesterol, cholesterol
is essential for the formation of clathrin-coated endocytic vesicles.
PMID- 10198051
TI - Tyrosine-phosphorylated caveolin-1: immunolocalization and molecular
characterization.
AB - Caveolin-1 was discovered as a major substrate for v-Src, but the effect of its
tyrosine phosphorylation has not been known. We generated a specific antibody
(PY14) to caveolin-1 phosphorylated at tyrosine 14 and studied the significance
of the modification. By Western blotting of lysates of v-Src-expressing cells,
PY14 recognized not only a 22-kDa band (the position of nonphosphorylated
caveolin-1) but bands at 23-24 and 25 kDa. Bands of slower mobility were
diminished by dephosphorylation and were also observed for mutant caveolin-1
lacking tyrosine 14. By immunofluorescence microscopy, PY14 did not label normal
cells but detected large dots in v-Src-expressing cells. Immunoelectron
microscopy revealed that the dots corresponded to aggregated caveolae and/or
vesicles of various sizes; besides, the label was observed in intramembrane
particle-free areas in the plasma membrane, which appeared to have been formed by
fusion of flattened caveolae. A positive reaction with PY14 was found in normal
cells after vanadate or pervanadate treatment; it occurred mainly at 22 kDa by
Western blotting and was not seen as large dots by immunofluorescence microscopy.
Detergent solubility, oligomerization, and association with caveolin-2 were
observed similarly for caveolin-1 in normal and v-Src-expressing cells. The
results indicate that phosphorylation of caveolin-1 in v-Src-expressing cells
occurs at multiple residues and induces flattening, aggregation, and fusion of
caveolae and/or caveolae-derived vesicles.
PMID- 10198052
TI - Regulation of ribosome biogenesis by the rapamycin-sensitive TOR-signaling
pathway in Saccharomyces cerevisiae.
AB - The TOR (target of rapamycin) signal transduction pathway is an important
mechanism by which cell growth is controlled in all eucaryotic cells.
Specifically, TOR signaling adjusts the protein biosynthetic capacity of cells
according to nutrient availability. In mammalian cells, one branch of this
pathway controls general translational initiation, whereas a separate branch
specifically regulates the translation of ribosomal protein (r-protein) mRNAs. In
Saccharomyces cerevisiae, the TOR pathway similarly regulates general
translational initiation, but its specific role in the synthesis of ribosomal
components is not well understood. Here we demonstrate that in yeast control of
ribosome biosynthesis by the TOR pathway is surprisingly complex. In addition to
general effects on translational initiation, TOR exerts drastic control over r
protein gene transcription as well as the synthesis and subsequent processing of
35S precursor rRNA. We also find that TOR signaling is a prerequisite for the
induction of r-protein gene transcription that occurs in response to improved
nutrient conditions. This induction has been shown previously to involve both the
Ras-adenylate cyclase as well as the fermentable growth medium-induced pathways,
and our results therefore suggest that these three pathways may be intimately
linked.
PMID- 10198053
TI - The tail of a yeast class V myosin, myo2p, functions as a localization domain.
AB - Myo2p is a yeast class V myosin that functions in membrane trafficking. To
investigate the function of the carboxyl-terminal-tail domain of Myo2p, we have
overexpressed this domain behind the regulatable GAL1 promoter (MYO2DN).
Overexpression of the tail domain of Myo2p results in a dominant-negative
phenotype that is phenotypically similar to a temperature-sensitive allele of
myo2, myo2-66. The tail domain of Myo2p is sufficient for localization at low-
expression levels and causes mislocalization of the endogenous Myo2p from sites
of polarized cell growth. Subcellular fractionation of polarized, mechanically
lysed yeast cells reveals that Myo2p is present predominantly in a 100,000 x g
pellet. The Myo2p in this pellet is not solubilized by Mg++-ATP or Triton X-100,
but is solubilized by high salt. Tail overexpression does not disrupt this
fractionation pattern, nor do mutations in sec4, sec3, sec9, cdc42, or myo2.
These results show that overexpression of the tail domain of Myo2p does not
compete with the endogenous Myo2p for assembly into a pelletable structure, but
does compete with the endogenous Myo2p for a factor that is necessary for
localization to the bud tip.
PMID- 10198054
TI - Uridine diphosphate-glucose transport into the endoplasmic reticulum of
Saccharomyces cerevisiae: in vivo and in vitro evidence.
AB - It has been proposed that synthesis of beta-1,6-glucan, one of Saccharomyces
cerevisiae cell wall components, is initiated by a uridine diphosphate (UDP)
glucose-dependent reaction in the lumen of the endoplasmic reticulum (ER).
Because this sugar nucleotide is not synthesized in the lumen of the ER, we have
examined whether or not UDP-glucose can be transported across the ER membrane. We
have detected transport of this sugar nucleotide into the ER in vivo and into ER
containing microsomes in vitro. Experiments with ER-containing microsomes showed
that transport of UDP-glucose was temperature dependent and saturable with an
apparent Km of 46 microM and a Vmax of 200 pmol/mg protein/3 min. Transport was
substrate specific because UDP-N-acetylglucosamine did not enter these vesicles.
Demonstration of UDP-glucose transport into the ER lumen in vivo was accomplished
by functional expression of Schizosaccharomyces pombe UDP-glucose:glycoprotein
glucosyltransferase (GT) in S. cerevisiae, which is devoid of this activity.
Monoglucosylated protein-linked oligosaccharides were detected in alg6 or alg5
mutant cells, which transfer Man9GlcNAc2 to protein; glucosylation was dependent
on the inhibition of glucosidase II or the disruption of the gene encoding this
enzyme. Although S. cerevisiae lacks GT, it contains Kre5p, a protein with
significant homology and the same size and subcellular location as GT. Deletion
mutants, kre5Delta, lack cell wall beta-1,6 glucan and grow very slowly.
Expression of S. pombe GT in kre5Delta mutants did not complement the slow-growth
phenotype, indicating that both proteins have different functions in spite of
their similarities.
PMID- 10198055
TI - Cloning and sequencing of a protein involved in phagosomal membrane fusion in
Paramecium.
AB - An mAb was raised to the C5 phagosomal antigen in Paramecium multimicronucleatum.
To determine its function, the cDNA and genomic DNA encoding C5 were cloned. This
antigen consisted of 315 amino acid residues with a predicted molecular weight of
36,594, a value similar to that determined by SDS-PAGE. Sequence comparisons
uncovered a low but significant homology with a Schizosaccharomyces pombe protein
and the C-terminal half of the beta-fructofuranosidase protein of Zymomonas
mobilis. Lacking an obvious transmembrane domain or a possible signal sequence at
the N terminus, C5 was predicted to be a soluble protein, whereas
immunofluorescence data showed that it was present on the membranes of vesicles
and digestive vacuoles (DVs). In cells that were minimally permeabilized but with
intact DVs, C5 was found to be located on the cytosolic surface of the DV
membranes. Immunoblotting of proteins from the purified and KCl-washed DVs showed
that C5 was tightly bound to the DV membranes. Cryoelectron microscopy also
confirmed that C5 was on the cytosolic surface of the discoidal vesicles,
acidosomes, and lysosomes, organelles known to fuse with the membranes of the
cytopharynx, the DVs of stages I (DV-I) and II (DV-II), respectively. Although C5
was concentrated more on the mature than on the young DV membranes, the striking
observation was that the cytopharyngeal membrane that is derived from the
discoidal vesicles was almost devoid of C5. Approximately 80% of the C5 was lost
from the discoidal vesicle-derived membrane after this membrane fused with the
cytopharyngeal membrane. Microinjection of the mAb to C5 greatly inhibited the
fusion of the discoidal vesicles with the cytopharyngeal membrane and thus the
incorporation of the discoidal vesicle membranes into the DV membranes. Taken
together, these results suggest that C5 is a membrane protein that is involved in
binding and/or fusion of the discoidal vesicles with the cytopharyngeal membrane
that leads to DV formation.
PMID- 10198056
TI - Two endoplasmic reticulum (ER) membrane proteins that facilitate ER-to-Golgi
transport of glycosylphosphatidylinositol-anchored proteins.
AB - Many eukaryotic cell surface proteins are anchored in the lipid bilayer through
glycosylphosphatidylinositol (GPI). GPI anchors are covalently attached in the
endoplasmic reticulum (ER). The modified proteins are then transported through
the secretory pathway to the cell surface. We have identified two genes in
Saccharomyces cerevisiae, LAG1 and a novel gene termed DGT1 (for "delayed GPI
anchored protein transport"), encoding structurally related proteins with
multiple membrane-spanning domains. Both proteins are localized to the ER, as
demonstrated by immunofluorescence microscopy. Deletion of either gene caused no
detectable phenotype, whereas lag1Delta dgt1Delta cells displayed growth defects
and a significant delay in ER-to-Golgi transport of GPI-anchored proteins,
suggesting that LAG1 and DGT1 encode functionally redundant or overlapping
proteins. The rate of GPI anchor attachment was not affected, nor was the
transport rate of several non-GPI-anchored proteins. Consistent with a role of
Lag1p and Dgt1p in GPI-anchored protein transport, lag1Delta dgt1Delta cells
deposit abnormal, multilayered cell walls. Both proteins have significant
sequence similarity to TRAM, a mammalian membrane protein thought to be involved
in protein translocation across the ER membrane. In vivo translocation studies,
however, did not detect any defects in protein translocation in lag1Delta
dgt1Delta cells, suggesting that neither yeast gene plays a role in this process.
Instead, we propose that Lag1p and Dgt1p facilitate efficient ER-to-Golgi
transport of GPI-anchored proteins.
PMID- 10198057
TI - Sla1p is a functionally modular component of the yeast cortical actin
cytoskeleton required for correct localization of both Rho1p-GTPase and Sla2p, a
protein with talin homology.
AB - SLA1 was identified previously in budding yeast in a genetic screen for mutations
that caused a requirement for the actin-binding protein Abp1p and was shown to be
required for normal cortical actin patch structure and organization. Here, we
show that Sla1p, like Abp1p, localizes to cortical actin patches. Furthermore,
Sla1p is required for the correct localization of Sla2p, an actin-binding protein
with homology to talin implicated in endocytosis, and the Rho1p-GTPase, which is
associated with the cell wall biosynthesis enzyme beta-1,3-glucan synthase.
Mislocalization of Rho1p in sla1 null cells is consistent with our observation
that these cells possess aberrantly thick cell walls. Expression of mutant forms
of Sla1p in which specific domains were deleted showed that the phenotypes
associated with the full deletion are functionally separable. In particular, a
region of Sla1p encompassing the third SH3 domain is important for growth at high
temperatures, for the organization of cortical actin patches, and for nucleated
actin assembly in a permeabilized yeast cell assay. The apparent redundancy
between Sla1p and Abp1p resides in the C-terminal repeat region of Sla1p. A
homologue of SLA1 was identified in Schizosaccharomyces pombe. Despite relatively
low overall sequence homology, this gene was able to rescue the temperature
sensitivity associated with a deletion of SLA1 in Saccharomyces cerevisiae.
PMID- 10198058
TI - The Yck2 yeast casein kinase 1 isoform shows cell cycle-specific localization to
sites of polarized growth and is required for proper septin organization.
AB - Casein kinase 1 protein kinases are ubiquitous and abundant Ser/Thr-specific
protein kinases with activity on acidic substrates. In yeast, the products of the
redundant YCK1 and YCK2 genes are together essential for cell viability. Mutants
deficient for these proteins display defects in cellular morphogenesis,
cytokinesis, and endocytosis. Yck1p and Yck2p are peripheral plasma membrane
proteins, and we report here that the localization of Yck2p within the membrane
is dynamic through the cell cycle. Using a functional green fluorescent protein
(GFP) fusion, we have observed that Yck2p is concentrated at sites of polarized
growth during bud morphogenesis. At cytokinesis, GFP-Yck2p becomes associated
with a ring at the bud neck and then appears as a patch of fluorescence,
apparently coincident with the dividing membranes. The bud neck association of
Yck2p at cytokinesis does not require an intact septin ring, and septin assembly
is altered in a Yck-deficient mutant. The sites of GFP-Yck2p concentration and
the defects observed for Yck-deficient cells together suggest that Yck plays
distinct roles in morphogenesis and cytokinesis that are effected by differential
localization.
PMID- 10198059
TI - Epigallocathechin-3 gallate selectively inhibits the PDGF-BB-induced
intracellular signaling transduction pathway in vascular smooth muscle cells and
inhibits transformation of sis-transfected NIH 3T3 fibroblasts and human
glioblastoma cells (A172).
AB - Enhanced activity of receptor tyrosine kinases such as the PDGF beta-receptor and
EGF receptor has been implicated as a contributing factor in the development of
malignant and nonmalignant proliferative diseases such as cancer and
atherosclerosis. Several epidemiological studies suggest that green tea may
prevent the development of cancer and atherosclerosis. One of the major
constituents of green tea is the polyphenol epigallocathechin-3 gallate (EGCG).
In an attempt to offer a possible explanation for the anti-cancer and anti
atherosclerotic activity of EGCG, we examined the effect of EGCG on the PDGF-BB-,
EGF-, angiotensin II-, and FCS-induced activation of the 44 kDa and 42 kDa
mitogen-activated protein (MAP) kinase isoforms (p44(mapk)/p42(mapk)) in cultured
vascular smooth muscle cells (VSMCs) from rat aorta. VSMCs were treated with EGCG
(1-100 microM) for 24 h and stimulated with the above mentioned agonists for
different time periods. Stimulation of the p44(mapk)/p42(mapk) was detected by
the enhanced Western blotting method using phospho-specific MAP kinase antibodies
that recognized the Tyr204-phosphorylated (active) isoforms. Treatment of VSMCs
with 10 and 50 microM EGCG resulted in an 80% and a complete inhibition of the
PDGF-BB-induced activation of MAP kinase isoforms, respectively. In striking
contrast, EGCG (1-100 microM) did not influence MAP kinase activation by EGF,
angiotensin II, and FCS. Similarly, the maximal effect of PDGF-BB on the c-fos
and egr-1 mRNA expression as well as on intracellular free Ca2+ concentration was
completely inhibited in EGCG-treated VSMCs, whereas the effect of EGF was not
affected. Quantification of the immunoprecipitated tyrosine-phosphorylated PDGF
Rbeta, phosphatidylinositol 3'-kinase, and phospholipase C-gamma1 by the enhanced
Western blotting method revealed that EGCG treatment effectively inhibits
tyrosine phosphorylation of these kinases in VSMCs. Furthermore, we show that
spheroid formation of human glioblastoma cells (A172) and colony formation of sis
transfected NIH 3T3 cells in semisolid agar are completely inhibited by 20-50
microM EGCG. Our findings demonstrate that EGCG is a selective inhibitor of the
tyrosine phosphorylation of PDGF-Rbeta and its downstream signaling pathway. The
present findings may partly explain the anti-cancer and anti-atherosclerotic
activity of green tea.
PMID- 10198060
TI - Detyrosination of tubulin regulates the interaction of intermediate filaments
with microtubules in vivo via a kinesin-dependent mechanism.
AB - Posttranslationally modified forms of tubulin accumulate in the subset of
stabilized microtubules (MTs) in cells but are not themselves involved in
generating MT stability. We showed previously that stabilized, detyrosinated
(Glu) MTs function to localize vimentin intermediate filaments (IFs) in
fibroblasts. To determine whether tubulin detyrosination or MT stability is the
critical element in the preferential association of IFs with Glu MTs, we
microinjected nonpolymerizable Glu tubulin into cells. If detyrosination is
critical, then soluble Glu tubulin should be a competitive inhibitor of the IF-MT
interaction. Before microinjection, Glu tubulin was rendered nonpolymerizable and
nontyrosinatable by treatment with iodoacetamide (IAA). Microinjected IAA-Glu
tubulin disrupted the interaction of IFs with MTs, as assayed by the collapse of
IFs to a perinuclear location, and had no detectable effect on the array of Glu
or tyrosinated MTs in cells. Conversely, neither IAA-tyrosinated tubulin nor
untreated Glu tubulin, which assembled into MTs, caused collapse of IFs when
microinjected. The epitope on Glu tubulin responsible for interfering with the
Glu MT-IF interaction was mapped by microinjecting tubulin fragments of alpha
tubulin. The 14-kDa C-terminal fragment of Glu tubulin (alpha-C Glu) induced IF
collapse, whereas the 36-kDa N-terminal fragment of alpha-tubulin did not alter
the IF array. The epitope required more than the detyrosination site at the C
terminus, because a short peptide (a 7-mer) mimicking the C terminus of Glu
tubulin did not disrupt the IF distribution. We previously showed that kinesin
may mediate the interaction of Glu MTs and IFs. In this study we found that
kinesin binding to MTs in vitro was inhibited by the same reagents (i.e., IAA-Glu
tubulin and alpha-C Glu) that disrupted the IF-Glu MT interaction in vivo. These
results demonstrate for the first time that tubulin detyrosination functions as a
signal for the recruitment of IFs to MTs via a mechanism that is likely to
involve kinesin.
PMID- 10198061
TI - beta-catenin can be transported into the nucleus in a Ran-unassisted manner.
AB - The nuclear accumulation of beta-catenin plays an important role in the
Wingless/Wnt signaling pathway. This study describes an examination of the
nuclear import of beta-catenin in living mammalian cells and in vitro semi-intact
cells. When injected into the cell cytoplasm, beta-catenin rapidly migrated into
the nucleus in a temperature-dependent and wheat germ agglutinin-sensitive
manner. In the cell-free import assay, beta-catenin rapidly migrates into the
nucleus without the exogenous addition of cytosol, Ran, or ATP/GTP. Cytoplasmic
injection of mutant Ran defective in its GTP hydrolysis did not prevent beta
catenin import. Studies using tsBN2, a temperature-sensitive mutant cell line
that possesses a point mutation in the RCC1 gene, showed that the import of beta
catenin is insensitive to nuclear Ran-GTP depletion. These results show that beta
catenin possesses the ability to constitutively translocate through the nuclear
pores in a manner similar to importin beta in a Ran-unassisted manner. We further
showed that beta-catenin also rapidly exits the nucleus in homokaryons,
suggesting that the regulation of nuclear levels of beta-catenin involves both
nuclear import and export of this molecule.
PMID- 10198062
TI - Elucidation of a PTS-carbohydrate chemotactic signal pathway in Escherichia coli
using a time-resolved behavioral assay.
AB - Chemotaxis of Escherichia coli toward phosphotransferase systems (PTSs)
carbohydrates requires phosphoenolpyruvate-dependent PTSs as well as the
chemotaxis response regulator CheY and its kinase, CheA. Responses initiated by
flash photorelease of a PTS substrates D-glucose and its nonmetabolizable analog
methyl alpha-D-glucopyranoside were measured with 33-ms time resolution using
computer-assisted motion analysis. This, together with chemotactic mutants, has
allowed us to map out and characterize the PTS chemotactic signal pathway. The
responses were absent in mutants lacking the general PTS enzymes EI or HPr,
elevated in PTS transport mutants, retarded in mutants lacking CheZ, a catalyst
of CheY autodephosphorylation, and severely reduced in mutants with impaired
methyl-accepting chemotaxis protein (MCP) signaling activity. Response kinetics
were comparable to those triggered by MCP attractant ligands over most of the
response range, the most rapid being 11.7 +/- 3.1 s-1. The response threshold was
<10 nM for glucose. Responses to methyl alpha-D-glucopyranoside had a higher
threshold, commensurate with a lower PTS affinity, but were otherwise kinetically
indistinguishable. These facts provide evidence for a single pathway in which the
PTS chemotactic signal is relayed rapidly to MCP-CheW-CheA signaling complexes
that effect subsequent amplification and slower CheY dephosphorylation. The high
sensitivity indicates that this signal is generated by transport-induced
dephosphorylation of the PTS rather than phosphoenolpyruvate consumption.
PMID- 10198063
TI - Kinase activity-dependent nuclear export opposes stress-induced nuclear
accumulation and retention of Hog1 mitogen-activated protein kinase in the
budding yeast Saccharomyces cerevisiae.
AB - Budding yeast adjusts to increases in external osmolarity via a specific mitogen
activated protein kinase signal pathway, the high-osmolarity glycerol response
(HOG) pathway. Studies with a functional Hog1-green fluorescent protein (GFP)
fusion reveal that even under nonstress conditions the mitogen-activated protein
kinase Hog1 cycles between cytoplasmic and nuclear compartments. The basal
distribution of the protein seems independent of its activator, Pbs2, and
independent of its phosphorylation status. Upon osmotic challenge, the Hog1-GFP
fusion becomes rapidly concentrated in the nucleus from which it is reexported
after return to an iso-osmotic environment or after adaptation to high
osmolarity. The preconditions and kinetics of increased nuclear localization
correlate with those found for the dual phosphorylation of Hog1-GFP. The duration
of Hog1 nuclear residence is modulated by the presence of the general stress
activators Msn2 and Msn4. Reexport of Hog1 to the cytoplasm does not require de
novo protein synthesis but depends on Hog1 kinase activity. Thus, at least three
different mechanisms contribute to the intracellular distribution pattern of
Hog1: phosphorylation-dependent nuclear accumulation, retention by nuclear
targets, and a kinase-induced export.
PMID- 10198064
TI - Dynamics of a chemoattractant receptor in living neutrophils during chemotaxis.
AB - Persistent directional movement of neutrophils in shallow chemotactic gradients
raises the possibility that cells can increase their sensitivity to the
chemotactic signal at the front, relative to the back. Redistribution of
chemoattractant receptors to the anterior pole of a polarized neutrophil could
impose asymmetric sensitivity by increasing the relative strength of detected
signals at the cell's leading edge. Previous experiments have produced
contradictory observations with respect to receptor location in moving
neutrophils. To visualize a chemoattractant receptor directly during chemotaxis,
we expressed a green fluorescent protein (GFP)-tagged receptor for a complement
component, C5a, in a leukemia cell line, PLB-985. Differentiated PLB-985 cells,
like neutrophils, adhere, spread, and polarize in response to a uniform
concentration of chemoattractant, and orient and crawl toward a micropipette
containing chemoattractant. Recorded in living cells, fluorescence of the tagged
receptor, C5aR-GFP, shows no apparent increase anywhere on the plasma membrane of
polarized and moving cells, even at the leading edge. During chemotaxis, however,
some cells do exhibit increased amounts of highly folded plasma membrane at the
leading edge, as detected by a fluorescent probe for membrane lipids; this is
accompanied by an apparent increase of C5aR-GFP fluorescence, which is directly
proportional to the accumulation of plasma membrane. Thus neutrophils do not
actively concentrate chemoattractant receptors at the leading edge during
chemotaxis, although asymmetrical distribution of membrane may enrich receptor
number, relative to adjacent cytoplasmic volume, at the anterior pole of some
polarized cells. This enrichment could help to maintain persistent migration in a
shallow gradient of chemoattractant.
PMID- 10198065
TI - Ligand-induced trafficking of the sphingosine-1-phosphate receptor EDG-1.
AB - The endothelial-derived G-protein-coupled receptor EDG-1 is a high-affinity
receptor for the bioactive lipid mediator sphingosine-1-phosphate (SPP). In the
present study, we constructed the EDG-1-green fluorescent protein (GFP) chimera
to examine the dynamics and subcellular localization of SPP-EDG-1 interaction.
SPP binds to EDG-1-GFP and transduces intracellular signals in a manner
indistinguishable from that seen with the wild-type receptor. Human embryonic
kidney 293 cells stably transfected with the EDG-1-GFP cDNA expressed the
receptor primarily on the plasma membrane. Exogenous SPP treatment, in a dose
dependent manner, induced receptor translocation to perinuclear vesicles with a
tau1/2 of approximately 15 min. The EDG-1-GFP-containing vesicles are distinct
from mitochondria but colocalize in part with endocytic vesicles and lysosomes.
Neither the low-affinity agonist lysophosphatidic acid nor other sphingolipids,
ceramide, ceramide-1-phosphate, or sphingosylphosphorylcholine, influenced
receptor trafficking. Receptor internalization was completely inhibited by
truncation of the C terminus. After SPP washout, EDG-1-GFP recycles back to the
plasma membrane with a tau1/2 of approximately 30 min. We conclude that the high
affinity ligand SPP specifically induces the reversible trafficking of EDG-1 via
the endosomal pathway and that the C-terminal intracellular domain of the
receptor is critical for this process.
PMID- 10198066
TI - The Drosophila melanogaster homologue of the Xeroderma pigmentosum D gene product
is located in euchromatic regions and has a dynamic response to UV light-induced
lesions in polytene chromosomes.
AB - The XPD/ERCC2/Rad3 gene is required for excision repair of UV-damaged DNA and is
an important component of nucleotide excision repair. Mutations in the XPD gene
generate the cancer-prone syndrome, xeroderma pigmentosum, Cockayne's syndrome,
and trichothiodystrophy. XPD has a 5'- to 3'-helicase activity and is a component
of the TFIIH transcription factor, which is essential for RNA polymerase II
elongation. We present here the characterization of the Drosophila melanogaster
XPD gene (DmXPD). DmXPD encodes a product that is highly related to its human
homologue. The DmXPD protein is ubiquitous during development. In embryos at the
syncytial blastoderm stage, DmXPD is cytoplasmic. At the onset of transcription
in somatic cells and during gastrulation in germ cells, DmXPD moves to the
nuclei. Distribution analysis in polytene chromosomes shows that DmXPD is highly
concentrated in the interbands, especially in the highly transcribed regions
known as puffs. UV-light irradiation of third-instar larvae induces an increase
in the signal intensity and in the number of sites where the DmXPD protein is
located in polytene chromosomes, indicating that the DmXPD protein is recruited
intensively in the chromosomes as a response to DNA damage. This is the first
time that the response to DNA damage by UV-light irradiation can be visualized
directly on the chromosomes using one of the TFIIH components.
PMID- 10198067
TI - RacF1, a novel member of the Rho protein family in Dictyostelium discoideum,
associates transiently with cell contact areas, macropinosomes, and phagosomes.
AB - Using a PCR approach we have isolated racF1, a novel member of the Rho family in
Dictyostelium. The racF1 gene encodes a protein of 193 amino acids and is
constitutively expressed throughout the Dictyostelium life cycle. Highest
identity (94%) was found to a RacF2 isoform, to Dictyostelium Rac1A, Rac1B, and
Rac1C (70%), and to Rac proteins of animal species (64-69%). To investigate the
role of RacF1 in cytoskeleton-dependent processes, we have fused it at its amino
terminus with green fluorescent protein (GFP) and studied the dynamics of
subcellular redistribution using a confocal laser scanning microscope and a
double-view microscope system. GFP-RacF1 was homogeneously distributed in the
cytosol and accumulated at the plasma membrane, especially at regions of
transient intercellular contacts. GFP-RacF1 also localized transiently to
macropinosomes and phagocytic cups and was gradually released within <1 min after
formation of the endocytic vesicle or the phagosome, respectively. On stimulation
with cAMP, no enrichment of GFP-RacF1 was observed in leading fronts, from which
it was found to be initially excluded. Cell lines were obtained using homologous
recombination that expressed a truncated racF1 gene lacking sequences encoding
the carboxyl-terminal region responsible for membrane targeting. These cells
displayed normal phagocytosis, endocytosis, and exocytosis rates. Our results
suggest that RacF1 associates with dynamic structures that are formed during
pinocytosis and phagocytosis. Although RacF1 appears not to be essential, it
might act in concert and/or share functions with other members of the Rho family
in the regulation of a subset of cytoskeletal rearrangements that are required
for these processes.
PMID- 10198068
TI - Overexpression of a kinase-deficient transforming growth factor-beta type II
receptor in mouse mammary stroma results in increased epithelial branching.
AB - Members of the transforming growth factor-beta (TGF-beta) superfamily signal
through heteromeric type I and type II serine/threonine kinase receptors.
Transgenic mice that overexpress a dominant-negative mutation of the TGF-beta
type II receptor (DNIIR) under the control of a metallothionein-derived promoter
(MT-DNIIR) were used to determine the role of endogenous TGF-betas in the
developing mammary gland. The expression of the dominant-negative receptor was
induced with zinc and was primarily localized to the stroma underlying the ductal
epithelium in the mammary glands of virgin transgenic mice from two separate
mouse lines. In MT-DNIIR virgin females treated with zinc, there was an increase
in lateral branching of the ductal epithelium. We tested the hypothesis that
expression of the dominant-negative receptor may alter expression of genes that
are expressed in the stroma and regulated by TGF-betas, potentially resulting in
the increased lateral branching seen in the MT-DNIIR mammary glands. The
expression of hepatocyte growth factor mRNA was increased in mammary glands from
transgenic animals relative to the wild-type controls, suggesting that this
factor may play a role in TGF-beta-mediated regulation of lateral branching. Loss
of responsiveness to TGF-betas in the mammary stroma resulted in increased
branching in mammary epithelium, suggesting that TGF-betas play an important role
in the stromal-epithelial interactions required for branching morphogenesis.
PMID- 10198069
TI - Architecture of the nuclear periphery of rat pachytene spermatocytes:
distribution of nuclear envelope proteins in relation to synaptonemal complex
attachment sites.
AB - The nucleus of spermatocytes provides during the first meiotic prophase an
interesting model for investigating relationships of the nuclear envelope (NE)
with components of the nuclear interior. During the pachytene stage, meiotic
chromosomes are synapsed via synaptonemal complexes (SCs) and attached through
both ends to the nuclear periphery. This association is dynamic because
chromosomes move during the process of synapsis and desynapsis that takes place
during meiotic prophase. The NE of spermatocytes possesses some peculiarities
(e.g., lower stability than in somatic cells, expression of short meiosis
specific lamin isoforms called C2 and B3) that could be critically involved in
this process. For better understanding of the association of chromosomes with the
nuclear periphery, in the present study we have investigated the distribution of
NE proteins in relation to SC attachment sites. A major outcome was the finding
that lamin C2 is distributed in the form of discontinuous domains at the NE of
spermatocytes and that SC attachment sites are embedded in these domains. Lamin
C2 appears to form part of larger structures as suggested by cell fractionation
experiments. According to these results, we propose that the C2-containing
domains represent local reinforcements of the NE that are involved in the proper
attachment of SCs.
PMID- 10198070
TI - Temporary disruption of the plasma membrane is required for c-fos expression in
response to mechanical stress.
AB - Mechanically stressed cells display increased levels of fos message and protein.
Although the intracellular signaling pathways responsible for FOS induction have
been extensively characterized, we still do not understand the nature of the
primary cell mechanotransduction event responsible for converting an externally
acting mechanical stressor into an intracellular signal cascade. We now report
that plasma membrane disruption (PMD) is quantitatively correlated on a cell-by
cell basis with fos protein levels expressed in mechanically injured monolayers.
When the population of PMD-affected cells in injured monolayers was selectively
prevented from responding to the injury, the fos response was completely ablated,
demonstrating that PMD is a requisite event. This PMD-dependent expression of fos
protein did not require cell exposure to cues inherent in release from cell-cell
contact inhibition or presented by denuded substratum, because it also occurred
in subconfluent monolayers. Fos expression also could not be explained by factors
released through PMD, because cell injury conditioned medium failed to elicit fos
expression. Translocation of the transcription factor NF-kappaB into the nucleus
may also be regulated by PMD, based on a quantitative correlation similar to that
found with fos. We propose that PMD, by allowing a flux of normally impermeant
molecules across the plasma membrane, mediates a previously unrecognized form of
cell mechanotransduction. PMD may thereby lead to cell growth or hypertrophy
responses such as those that are present normally in mechanically stressed
skeletal muscle and pathologically in the cardiovascular system.
PMID- 10198073
TI - Genes, genomes, genomics. What can plant biologists expect from the 1998 national
science foundation plant genome research program?
PMID- 10198071
TI - Electric field-directed cell motility involves up-regulated expression and
asymmetric redistribution of the epidermal growth factor receptors and is
enhanced by fibronectin and laminin.
AB - Wounding corneal epithelium establishes a laterally oriented, DC electric field
(EF). Corneal epithelial cells (CECs) cultured in similar physiological EFs
migrate cathodally, but this requires serum growth factors. Migration depends
also on the substrate. On fibronectin (FN) or laminin (LAM) substrates in EF,
cells migrated faster and more directly cathodally. This also was serum
dependent. Epidermal growth factor (EGF) restored cathodal-directed migration in
serum-free medium. Therefore, the hypothesis that EGF is a serum constituent
underlying both field-directed migration and enhanced migration on ECM molecules
was tested. We used immunofluorescence, flow cytometry, and confocal microscopy
and report that 1) EF exposure up-regulated the EGF receptor (EGFR); so also did
growing cells on substrates of FN or LAM; and 2) EGFRs and actin accumulated in
the cathodal-directed half of CECs, within 10 min in EF. The cathodal asymmetry
of EGFR and actin staining was correlated, being most marked at the cell
substrate interface and showing similar patterns of asymmetry at various levels
through a cell. At the cell-substrate interface, EGFRs and actin frequently
colocalized as interdigitated, punctate spots resembling tank tracks. Cathodal
accumulation of EGFR and actin did not occur in the absence of serum but were
restored by adding ligand to serum-free medium. Inhibition of MAPK, one second
messenger engaged by EGF, significantly reduced EF-directed cell migration.
Transforming growth factor beta and fibroblast growth factor also restored
cathodal-directed cell migration in serum-free medium. However, longer EF
exposure was needed to show clear asymmetric distribution of the receptors for
transforming growth factor beta and fibroblast growth factor. We propose that up
regulated expression and redistribution of EGFRs underlie cathodal-directed
migration of CECs and directed migration induced by EF on FN and LAM.
PMID- 10198072
TI - Transmembrane insertion of the Toxoplasma gondii GRA5 protein occurs after
soluble secretion into the host cell.
AB - The intracellular parasite Toxoplasma gondii resides within a specialized
compartment, the parasitophorous vacuole (PV), that resists fusion with host cell
endocytic and lysosomal compartments. The PV is extensively modified by secretion
of parasite proteins, including the dense granule protein GRA5 that is
specifically targeted to the delimiting membrane of the PV (PVM). We show here
that GRA5 is present both in a soluble form and in hydrophobic aggregates. GRA5
is secreted as a soluble form into the PV after which it becomes stably
associated with the PVM. Topological studies demonstrated that GRA5 was inserted
into the PVM as a transmembrane protein with its N-terminal domain extending into
the cytoplasm and its C terminus in the vacuole lumen. Deletion of 8 of the 18
hydrophobic amino acids of the single predicted transmembrane domain resulted in
the failure of GRA5 to associate with the PVM; yet it remained correctly packaged
in the dense granules and was secreted as a soluble protein into the PV.
Collectively, these studies demonstrate that the secretory pathway in Toxoplasma
is unusual in two regards; it allows soluble export of proteins containing
typical transmembrane domains and provides a mechanism for their insertion into a
host cell membrane after secretion from the parasite.
PMID- 10198074
TI - Protein targeting to the nuclear pore. What can we learn from plants?
PMID- 10198076
TI - A computer-assisted personalized approach in an undergraduate plant physiology
class
AB - We used Computer-Assisted Personalized Approach (CAPA), a networked teaching and
learning tool that generates computer individualized homework problem sets, in
our large-enrollment introductory plant physiology course. We saw significant
improvement in student examination performance with regular homework assignments,
with CAPA being an effective and efficient substitute for hand-graded homework.
Using CAPA, each student received a printed set of similar but individualized
problems of a conceptual (qualitative) and/or quantitative nature with quality
graphics. Because each set of problems is unique, students were encouraged to
work together to clarify concepts but were required to do their own work for
credit. Students could enter answers multiple times without penalty, and they
were able to obtain immediate feedback and hints until the due date. These
features increased student time on task, allowing higher course standards and
student achievement in a diverse student population. CAPA handles routine tasks
such as grading, recording, summarizing, and posting grades. In anonymous
surveys, students indicated an overwhelming preference for homework in CAPA
format, citing several features such as immediate feedback, multiple tries, and
on-line accessibility as reasons for their preference. We wrote and used more
than 170 problems on 17 topics in introductory plant physiology, cataloging them
in a computer library for general access. Representative problems are compared
and discussed.
PMID- 10198075
TI - Identification of a calmodulin-regulated Ca2+-ATPase in the endoplasmic
reticulum.
AB - A unique subfamily of calmodulin-dependent Ca2+-ATPases was recently identified
in plants. In contrast to the most closely related pumps in animals, plasma
membrane-type Ca2+-ATPases, members of this new subfamily are distinguished by a
calmodulin-regulated autoinhibitor located at the N-terminal instead of a C
terminal end. In addition, at least some isoforms appear to reside in non-plasma
membrane locations. To begin delineating their functions, we investigated the
subcellular localization of isoform ACA2p (Arabidopsis Ca2+-ATPase, isoform 2
protein) in Arabidopsis. Here we provide evidence that ACA2p resides in the
endoplasmic reticulum (ER). In buoyant density sucrose gradients performed with
and without Mg2+, ACA2p cofractionated with an ER membrane marker and a typical
"ER-type" Ca2+-ATPase, ACA3p/ECA1p. To visualize its subcellular localization,
ACA2p was tagged with a green fluorescence protein at its C terminus (ACA2-GFPp)
and expressed in transgenic Arabidopsis. We collected fluorescence images from
live root cells using confocal and computational optical-sectioning microscopy.
ACA2-GFPp appeared as a fluorescent reticulum, consistent with an ER location. In
addition, we observed strong fluorescence around the nuclei of mature epidermal
cells, which is consistent with the hypothesis that ACA2p may also function in
the nuclear envelope. An ER location makes ACA2p distinct from all other
calmodulin-regulated pumps identified in plants or animals.
PMID- 10198077
TI - Posttranscriptional gene silencing in transgenic sugarcane. Dissection Of
homology-dependent virus resistance in a monocot that has a complex polyploid
genome
AB - RNA-mediated, posttranscriptional gene silencing has been determined as the
molecular mechanism underlying transgenic virus resistance in many plant virus
dicot host plant systems. In this paper we show that transgenic virus resistance
in sugarcane (Saccharum spp. hybrid) is based on posttranscriptional gene
silencing. The resistance is derived from an untranslatable form of the sorghum
mosaic potyvirus strain SCH coat protein (CP) gene. Transgenic sugarcane plants
challenged with sorghum mosaic potyvirus strain SCH had phenotypes that ranged
from fully susceptible to completely resistant, and a recovery phenotype was also
observed. Clones derived from the same transformation event or obtained after
vegetative propagation could display different levels of virus resistance,
suggesting the involvement of a quantitative component in the resistance
response. Most resistant plants displayed low or undetectable steady-state CP
transgene mRNA levels, although nuclear transcription rates were high. Increased
DNA methylation was observed in the transcribed region of the CP transgenes in
most of these plants. Collectively, these characteristics indicate that an RNA
mediated, homology-dependent mechanism is at the base of the virus resistance.
This work extends posttranscriptional gene silencing and homology-dependent virus
resistance, so far observed only in dicots, to an agronomically important,
polyploid monocot.
PMID- 10198078
TI - Extragenic suppressors of the Arabidopsis gai mutation alter the dose-response
relationship of diverse gibberellin responses.
AB - Active gibberellins (GAs) are endogenous factors that regulate plant growth and
development in a dose-dependent fashion. Mutant plants that are GA deficient, or
exhibit reduced GA responses, display a characteristic dwarf phenotype.
Extragenic suppressor analysis has resulted in the isolation of Arabidopsis
mutations, which partially suppress the dwarf phenotype conferred by GA
deficiency and reduced GA-response mutations. Here we describe detailed studies
of the effects of two of these suppressors, spy-7 and gar2-1, on several
different GA-responsive growth processes (seed germination, vegetative growth,
stem elongation, chlorophyll accumulation, and flowering) and on the in planta
amounts of active and inactive GA species. The results of these experiments show
that spy-7 and gar2-1 affect the GA dose-response relationship for a wide range
of GA responses and suggest that all GA-regulated processes are controlled
through a negatively acting GA-signaling pathway.
PMID- 10198079
TI - Chloroplast-targeted ERD1 protein declines but its mRNA increases during
senescence in Arabidopsis.
AB - Arabidopsis ERD1 is a ClpC-like protein that sequence analysis suggests may
interact with the chloroplast-localized ClpP protease to facilitate proteolysis.
The mRNA encoded by the ERD1 gene has previously been shown to accumulate in
response to senescence and to a variety of stresses and hormones. Here we show
that the ERD1 protein, in contrast to the ERD1 mRNA, strongly declines in
abundance with age, becoming undetectable in fully expanded leaves. Sequence
analysis also suggests that ERD1 is chloroplast targeted, and we show in an in
vitro system that the native protein is properly imported, processed, and present
within the soluble fraction of the chloroplast, presumably the stroma. We show
that ClpP protein, which is also present in the stroma, declines with age in
parallel with ERD1. These results are consistent with the interaction of ERD1 and
ClpP, but they suggest that it is unlikely that either plays a major role during
senescence. Certain other chloroplast proteins decline with age coordinately with
ERD1 and ClpP, suggesting that these declines are markers of an early age
mediated change that occurs within the chloroplast.
PMID- 10198080
TI - The decisive step in betaxanthin biosynthesis is a spontaneous reaction1
AB - Experiments were performed to confirm that the aldimine bond formation is a
spontaneous reaction, because attempts to find an enzyme catalyzing the last
decisive step in betaxanthin biosynthesis, the aldimine formation, failed.
Feeding different amino acids to betalain-forming hairy root cultures of yellow
beet (Beta vulgaris L. subsp. vulgaris "Golden Beet") showed that all amino acids
(S- and R-forms) led to the corresponding betaxanthins. We observed neither an
amino acid specificity nor a stereoselectivity in this process. In addition,
increasing the endogenous phenylalanine (Phe) level by feeding the Phe ammonia
lyase inhibitor 2-aminoindan 2-phosphonic acid yielded the Phe-derived
betaxanthin. Feeding amino acids or 2-aminoindan 2-phosphonic acid to hypocotyls
of fodder beet (B. vulgaris L. subsp. vulgaris "Altamo") plants led to the same
results. Furthermore, feeding cyclo-3-(3,4-dihydroxyphenyl)-alanine (cyclo-Dopa)
to these hypocotyls resulted in betanidin formation, indicating that the decisive
step in betacyanin formation proceeds spontaneously. Finally, feeding betalamic
acid to broad bean (Vicia faba L.) seedlings, which are known to accumulate high
levels of Dopa but do not synthesize betaxanthins, resulted in the formation of
dopaxanthin. These results indicate that the condensation of betalamic acid with
amino acids (possibly including cyclo-Dopa or amines) in planta is a spontaneous,
not an enzyme-catalyzed reaction.
PMID- 10198081
TI - The relationship between photosynthesis and a mastoparan-induced hypersensitive
response in isolated mesophyll cells
AB - The G-protein activator mastoparan (MP) was found to elicit the hypersensitive
response (HR) in isolated Asparagus sprengeri mesophyll cells at micromolar
concentrations. The HR was characterized by cell death, extracellular
alkalinization, and an oxidative burst, indicated by the reduction of molecular
O2 to O2. To our knowledge, this study was the first to monitor photosynthesis
during the HR. MP had rapid and dramatic effects on photosynthetic electron
transport and excitation energy transfer as determined by variable chlorophyll a
fluorescence measurements. A large increase in nonphotochemical quenching of
chlorophyll a fluorescence accompanied the initial stages of the oxidative burst.
The minimal level of fluorescence was also quenched, which suggests the origin of
this nonphotochemical quenching to be a decrease in the antenna size of
photosystem II. In contrast, photochemical quenching of fluorescence decreased
dramatically during the latter stages of the oxidative burst, indicating a
somewhat slower inhibition of photosystem II electron transport. The net
consumption of O2 and the initial rate of O2 uptake, elicited by MP, were higher
in the light than in the dark. These data indicate that light enhances the
oxidative burst and suggest a complex relationship between photosynthesis and the
HR.
PMID- 10198083
TI - Hypersensitive cell death and papilla formation in barley attacked by the powdery
mildew fungus are associated with hydrogen peroxide but not with salicylic acid
accumulation
AB - We analyzed the pathogenesis-related generation of H2O2 using the microscopic
detection of 3,3-diaminobenzidine polymerization in near-isogenic barley (Hordeum
vulgare L.) lines carrying different powdery mildew (Blumeria graminis f.sp.
hordei) resistance genes, and in a line expressing chemically activated
resistance after treatment with 2,6-dichloroisonicotinic acid (DCINA).
Hypersensitive cell death in Mla12 and Mlg genotypes or after chemical activation
by DCINA was associated with H2O2 accumulation throughout attacked cells.
Formation of cell wall appositions (papillae) mediated in Mlg and mlo5 genotypes
and in DCINA-activated plants was paralleled by H2O2 accumulation in effective
papillae and in cytosolic vesicles of up to 2 MUm in diameter near the papillae.
H2O2 was not detected in ineffective papillae of cells that had been successfully
penetrated by the fungus. These findings support the hypothesis that H2O2 may
play a substantial role in plant defense against the powdery mildew fungus. We
did not detect any accumulation of salicylic acid in primary leaves after
inoculation of the different barley genotypes, indicating that these defense
responses neither relied on nor provoked salicylic acid accumulation in barley.
PMID- 10198082
TI - Fusicoccin, 14-3-3 proteins, and defense responses in tomato plants.
AB - Fusicoccin (FC) is a fungal toxin that activates the plant plasma membrane H+
ATPase by binding with 14-3-3 proteins, causing membrane hyperpolarization. Here
we report on the effect of FC on a gene-for-gene pathogen-resistance response and
show that FC application induces the expression of several genes involved in
plant responses to pathogens. Ten members of the FC-binding 14-3-3 protein gene
family were isolated from tomato (Lycopersicon esculentum) to characterize their
role in defense responses. Sequence analysis is suggestive of common biochemical
functions for these tomato 14-3-3 proteins, but their genes showed different
expression patterns in leaves after challenges. Different specific subsets of 14
3-3 genes were induced after treatment with FC and during a gene-for-gene
resistance response. Possible roles for the H+-ATPase and 14-3-3 proteins in
responses to pathogens are discussed.
PMID- 10198084
TI - Molecular cloning and characterization of apricot fruit polyphenol oxidase.
AB - A reverse transcriptase-polymerase chain reaction experiment was done to
synthesize a homologous polyphenol oxidase (PPO) probe from apricot (Prunus
armeniaca var Bergeron) fruit. This probe was further used to isolate a full
length PPO cDNA, PA-PPO (accession no. AF020786), from an immature-green fruit
cDNA library. PA-PPO is 2070 bp long and contains a single open reading frame
encoding a PPO precursor peptide of 597 amino acids with a calculated molecular
mass of 67.1 kD and an isoelectric point of 6.84. The mature protein has a
predicted molecular mass of 56.2 kD and an isoelectric point of 5.84. PA-PPO
belongs to a multigene family. The gene is highly expressed in young, immature
green fruit and is turned off early in the ripening process. The ratio of PPO
protein to total proteins per fruit apparently remains stable regardless of the
stage of development, whereas PPO specific activity peaks at the breaker stage.
These results suggest that, in addition to a transcriptional control of PPO
expression, other regulation factors such as translational and posttranslational
controls also occur.
PMID- 10198085
TI - Long-day up-regulation of a GAMYB gene during Lolium temulentum inflorescence
formation.
AB - Long-day exposure of the grass Lolium temulentum may regulate flowering via
changes in gibberellin (GA) levels. Therefore, we have examined both GA levels
and expression of a MYB transcription factor that is specific to the GA signal
transduction pathway in monocots. This MYB gene from L. temulentum shows over 90%
nucleotide identity with the barley and rice GAMYB genes, and, like them,
gibberellic acid (GA3) up-regulates its expression in the seed. Furthermore,
cDNAs of both the barley and L. temulentum GAMYB show the same simple patterns of
hybridization with digests of L. temulentum genomic DNA. Compared with vegetative
shoot apices of L. temulentum, the in situ mRNA expression of LtGAMYB does not
change during the earliest steps of "floral" initiation at the apex. However, by
100 h (the double-ridge stage of flowering) its expression increased
substantially and was highest in the terminal and lateral spikelet sites.
Thereafter, expression declined overall but then increased within stamen
primordia. Prior to increased LtGAMYB expression, long-day exposure sufficient to
induce flowering led to increased (5- to 20-fold) levels of GA1 and GA4 in the
leaf. Thus, increases first in GA level in the leaf followed by increased
expression of LtGAMYB in the apex suggest important signaling and/or response
roles in flowering.
PMID- 10198086
TI - Cucumber cotyledon lipoxygenase during postgerminative growth. Its expression and
action on lipid bodies.
AB - In cucumber (Cucumis sativus), high lipoxygenase-1 (LOX-1) activity has been
detected in the soluble fraction prepared from cotyledons of germinating seeds,
and the involvement of this enzyme in lipid turnover has been suggested (K.
Matsui, M. Irie, T. Kajiwara, A. Hatanaka [1992] Plant Sci 85: 23-32; I.
Fuessner, C. Wasternack, H. Kindl, H. Kuhn [1995] Proc Natl Acad Sci USA 92:
11849-11853). In this study we have investigated the expression of the gene lox
1, corresponding to the LOX-1 enzyme. LOX-1 expression is highly coordinated with
that of a typical glyoxysomal enzyme, isocitrate lyase, during the
postgerminative stage of cotyledon development. In contrast, although icl
transcripts accumulated in tissue during in vitro senescence, no accumulation of
lox-1 mRNA could be observed, suggesting that lox-1 plays a specialized role in
fat mobilization. LOX-1 is also known to be a major lipid body protein. The
partial peptide sequences of purified LOX-1 and lipid body LOX-1 entirely
coincided with that deduced from the lox-1 cDNA sequence. The data strongly
suggest that LOX-1 and lipid body LOX-1 are derived from a single gene and that
LOX-1 can exist both in the cytosol and on the lipid bodies. We constructed an in
vitro oxygenation system to address the mechanism of this dual localization and
to investigate the action of LOX-1 on lipids in the lipid bodies. LOX-1 cannot
act on the lipids in intact lipid bodies, although degradation of lipid body
proteins, either during seedling growth or by treatment with trypsin, allows
lipid bodies to become susceptible to LOX-1. We discuss the role of LOX-1 in fat
mobilization and its mechanism of action.
PMID- 10198087
TI - Involvement of the octadecanoid pathway and protein phosphorylation in fungal
elicitor-induced expression of terpenoid indole alkaloid biosynthetic genes in
catharanthus roseus
AB - Two key genes in terpenoid indole alkaloid biosynthesis, Tdc and Str, encoding
tryptophan decarboxylase and strictosidine synthase, respectively, are
coordinately induced by fungal elicitors in suspension-cultured Catharanthus
roseus cells. We have studied the roles of the jasmonate biosynthetic pathway and
of protein phosphorylation in signal transduction initiated by a partially
purified elicitor from yeast extract. In addition to activating Tdc and Str gene
expression, the elicitor also induced the biosynthesis of jasmonic acid. The
jasmonate precursor alpha-linolenic acid or methyl jasmonate (MeJA) itself
induced Tdc and Str gene expression when added exogenously. Diethyldithiocarbamic
acid, an inhibitor of jasmonate biosynthesis, blocked both the elicitor-induced
formation of jasmonic acid and the activation of terpenoid indole alkaloid
biosynthetic genes. The protein kinase inhibitor K-252a abolished both elicitor
induced jasmonate biosynthesis and MeJA-induced Tdc and Str gene expression.
Analysis of the expression of Str promoter/gusA fusions in transgenic C. roseus
cells showed that the elicitor and MeJA act at the transcriptional level. These
results demonstrate that the jasmonate biosynthetic pathway is an integral part
of the elicitor-triggered signal transduction pathway that results in the
coordinate expression of the Tdc and Str genes and that protein kinases act both
upstream and downstream of jasmonates.
PMID- 10198088
TI - An allele of the ripening-specific 1-aminocyclopropane-1-carboxylic acid synthase
gene (ACS1) in apple fruit with a long storage life.
AB - An allele of the 1-aminocyclopropane-1-carboxylic acid (ACC) synthase gene (Md
ACS1), the transcript and translated product of which have been identified in
ripening apples (Malus domestica), was isolated from a genomic library of the
apple cultivar, Golden Delicious. The predicted coding region of this allele
(ACS1-2) showed that seven nucleotide substitutions in the corresponding region
of ACS1-1 resulted in just one amino acid transition. A 162-bp sequence
characterized as a short interspersed repetitive element retrotransposon was
inserted in the 5'-flanking region of ACS1-2 corresponding to position -781 in
ACS1-1. The XhoI site located near the 3' end of the predicted coding region of
ACS1-2 was absent from the reverse transcriptase-polymerase chain reaction
product, revealing that exclusive transcription from ACS1-1 occurs during
ripening of cv Golden Delicious fruit. DNA gel-blot and polymerase chain reaction
analyses of genomic DNAs showed clearly that apple cultivars were either
heterozygous for ACS1-1 and ACS1-2 or homozygous for each type. RNA gel-blot
analysis of the ACS1-2 homozygous Fuji apple, which produces little ethylene and
has a long storage life, demonstrated that the level of transcription from ACS1-2
during the ripening stage was very low.
PMID- 10198090
TI - A cross-polarization, magic-angle-spinning, 13C-nuclear-magnetic-resonance study
of polysaccharides in sugar beet cell walls
AB - Solid-state nuclear magnetic resonance relaxation experiments were used to study
the rigidity and spatial proximity of polymers in sugar beet (Beta vulgaris) cell
walls. Proton T1rho decay and cross-polarization patterns were consistent with
the presence of rigid, crystalline cellulose microfibrils with a diameter of
approximately 3 nm, mobile pectic galacturonans, and highly mobile arabinans. A
direct-polarization, magic-angle-spinning spectrum recorded under conditions
adapted to mobile polymers showed only the arabinans, which had a conformation
similar to that of beet arabinans in solution. These cell walls contained very
small amounts of hemicellulosic polymers such as xyloglucan, xylan, and mannan,
and no arabinan or galacturonan fraction closely associated with cellulose
microfibrils, as would be expected of hemicelluloses. Cellulose microfibrils in
the beet cell walls were stable in the absence of any polysaccharide coating.
PMID- 10198089
TI - Identification, separation, and characterization of acyl-coenzyme A
dehydrogenases involved in mitochondrial beta-oxidation in higher plants
AB - The existence in higher plants of an additional beta-oxidation system in
mitochondria, besides the well-characterized peroxisomal system, is often
considered controversial. Unequivocal demonstration of beta-oxidation activity in
mitochondria should rely on identification of the enzymes specific to
mitochondrial beta-oxidation. Acyl-coenzyme A dehydrogenase (ACAD) (EC
1.3.99.2,3) activity was detected in purified mitochondria from maize (Zea mays
L.) root tips and from embryonic axes of early-germinating sunflower (Helianthus
annuus L.) seeds, using as the enzyme assay the reduction of 2,6
dichlorophenolindophenol, with phenazine methosulfate as the intermediate
electron carrier. Subcellular fractionation showed that this ACAD activity was
associated with mitochondrial fractions. Comparison of ACAD activity in
mitochondria and acyl-coenzyme A oxidase activity in peroxisomes showed
differences of substrate specificities. Embryonic axes of sunflower seeds were
used as starting material for the purification of ACADs. Two distinct ACADs, with
medium-chain and long-chain substrate specificities, respectively, were separated
by their chromatographic behavior, which was similar to that of mammalian ACADs.
The characterization of these ACADs is discussed in relation to the
identification of expressed sequenced tags corresponding to ACADs in cDNA
sequence analysis projects and with the potential roles of mitochondrial beta
oxidation in higher plants.
PMID- 10198091
TI - Cyanide-resistant, ATP-synthesis-sustained, and uncoupling-protein-sustained
respiration during postharvest ripening of tomato fruit
AB - Tomato (Lycopersicon esculentum) mitochondria contain both alternative oxidase
(AOX) and uncoupling protein as energy-dissipating systems that can decrease the
efficiency of oxidative phosphorylation. We followed the cyanide (CN)-resistant,
ATP-synthesis-sustained, and uncoupling-protein-sustained respiration of isolated
mitochondria, as well as the immunologically detectable levels of uncoupling
protein and AOX, during tomato fruit ripening from the mature green stage to the
red stage. The AOX protein level and CN-resistant respiration of isolated
mitochondria decreased with ripening from the green to the red stage. The ATP
synthesis-sustained respiration followed the same behavior. In contrast, the
level of uncoupling protein and the total uncoupling-protein-sustained
respiration of isolated mitochondria decreased from only the yellow stage on. We
observed an acute inhibition of the CN-resistant respiration by linoleic acid in
the micromolar range. These results suggest that the two energy-dissipating
systems could have different roles during the ripening process.
PMID- 10198092
TI - Changes in phosphoinositide metabolism with days in culture affect signal
transduction pathways in galdieria sulphuraria
AB - The metabolism of phosphatidylinositol-4,5-bisphosphate (PIP2) changed during the
culture period of the thermoacidophilic red alga Galdieria sulphuraria. Seven
days after inoculation, the amount of PIP2 in the cells was 910 +/- 100 pmol g-1
fresh weight; by 12 d, PIP2 levels increased to 1200 +/- 150 pmol g-1 fresh
weight. In vitro assays indicated that phosphatidylinositol monophosphate (PIP)
kinase specific activity increased from 75 to 230 pmol min-1 mg-1 protein between
d 7 and 12. When G. sulphuraria cells were osmostimulated, transient increases of
up to 4-fold could be observed in inositol-1,4,5-trisphosphate (IP3) levels
within 90 s, regardless of the age of the cells. In d-12 cells, the increase in
IP3 was preceded by a transient increase of up to 5-fold in specific PIP kinase
activity, whereas no such increase was detected after osmostimulation of d-7
cells. The increase in PIP kinase activity before IP3 signaling in d-12 cells
indicates that there is an additional pathway for regulation of phosphoinositide
metabolism after stimulation other than an initial activation of phospholipase C.
Also, the rapid activation of PIP2 biosynthesis in cells with already-high PIP2
levels suggests that the PIP2 present was not available for signal transduction.
By comparing the response of the cells at d 7 and 12, we have identified two
potentially distinct pools of PIP2.
PMID- 10198093
TI - Cloning and characterization of TPE4A, a thiol-protease gene induced during ovary
senescence and seed germination in pea.
AB - A cDNA clone encoding a thiol-protease (TPE4A) was isolated from senescent
ovaries of pea (Pisum sativum) by reverse transcriptase-polymerase chain
reaction. The deduced amino acid sequence of TPE4A has the conserved catalytic
amino acids of papain. It is very similar to VSCYSPROA, a thiol-protease induced
during seed germination in common vetch. TPE4A mRNA levels increase during the
senescence of unpollinated pea ovaries and are totally suppressed by treatment
with gibberellic acid. In situ hybridization indicated that TPE4A mRNA
distribution in senescent pea ovaries is different from that of previously
reported thiol-proteases induced during senescence, suggesting the involvement of
different proteases in the mobilization of proteins from senescent pea ovaries.
TPE4A is also induced during the germination of pea seeds, indicating that a
single protease gene can be induced during two different physiological processes,
senescence and germination, both of which require protein mobilization.
PMID- 10198094
TI - Proline accumulation in maize (Zea mays L.) primary roots at low water
potentials. II. Metabolic source of increased proline deposition in the
elongation zone
AB - The proline (Pro) concentration increases greatly in the growing region of maize
(Zea mays L.) primary roots at low water potentials (psiw), largely as a result
of an increased net rate of Pro deposition. Labeled glutamate (Glu), ornithine
(Orn), or Pro was supplied specifically to the root tip of intact seedlings in
solution culture at high and low psiw to assess the relative importance of Pro
synthesis, catabolism, utilization, and transport in root-tip Pro deposition.
Labeling with [3H]Glu indicated that Pro synthesis from Glu did not increase
substantially at low psiw and accounted for only a small fraction of the Pro
deposition. Labeling with [14C]Orn showed that Pro synthesis from Orn also could
not be a substantial contributor to Pro deposition. Labeling with [3H]Pro
indicated that neither Pro catabolism nor utilization in the root tip was
decreased at low psiw. Pro catabolism occurred at least as rapidly as Pro
synthesis from Glu. There was, however, an increase in Pro uptake at low psiw,
which suggests increased Pro transport. Taken together, the data indicate that
increased transport of Pro to the root tip serves as the source of low-psiw
induced Pro accumulation. The possible significance of Pro catabolism in
sustaining root growth at low psiw is also discussed.
PMID- 10198095
TI - Antifreeze proteins in winter rye leaves form oligomeric complexes
AB - Antifreeze proteins (AFPs) similar to three pathogenesis-related proteins, a
glucanase-like protein (GLP), a chitinase-like protein (CLP), and a thaumatin
like protein (TLP), accumulate during cold acclimation in winter rye (Secale
cereale) leaves, where they are thought to modify the growth of intercellular ice
during freezing. The objective of this study was to characterize the rye AFPs in
their native forms, and our results show that these proteins form oligomeric
complexes in vivo. Nine proteins were separated by native-polyacrylamide gel
electrophoresis from apoplastic extracts of cold-acclimated winter rye leaves.
Seven of these proteins exhibited multiple polypeptides when denatured and
separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. After
isolation of the individual proteins, six were shown by immunoblotting to contain
various combinations of GLP, CLP, and TLP in addition to other unidentified
proteins. Antisera produced against individual cold-induced winter rye GLP, CLP,
and TLP all dramatically inhibited glucanase activity in apoplastic extracts from
cold-acclimated winter rye leaves, and each antiserum precipitated all three
proteins. These results indicate that each of the polypeptides may be exposed on
the surface of the protein complexes. By forming oligomeric complexes, AFPs may
form larger surfaces to interact with ice, or they may simply increase the mass
of the protein bound to ice. In either case, the complexes of AFPs may inhibit
ice growth and recrystallization more effectively than the individual
polypeptides.
PMID- 10198096
TI - Subcellular distribution and tissue expression of phospholipase Dalpha, Dbeta,
and Dgamma in Arabidopsis.
AB - Three phospholipase Ds (PLDs; EC 3.1.4.4) have been cloned from Arabidopsis, and
they exhibit two distinct types of activities: polyphosphoinositide-requiring
PLDbeta and PLDgamma, and polyphosphoinositide-independent PLDalpha. In
subcellular fractions of Arabidopsis leaves, PLDalpha and PLDgamma were both
present in the plasma membrane, intracellular membranes, mitochondria, and
clathrin-coated vesicles, but their relative levels differed in these fractions.
In addition, PLDgamma was detected in the nuclear fraction. In contrast, PLDbeta
was not detectable in any of the subcellular fractions. PLDalpha activity was
higher in the metabolically more active organs such as flowers, siliques, and
roots than in dry seeds and mature leaves, whereas the polyphosphoinositide
dependent PLD activity was greater in older, senescing leaves than in other
organs. PLDbeta mRNA accumulated at a lower level than the PLDalpha and PLDgamma
transcripts in most organs, and the expression pattern of the PLDbeta mRNA also
differed from that of PLDalpha and PLDgamma in different organs. Collectively,
these data demonstrated that PLDalpha, PLDbeta, and PLDgamma have different
patterns of subcellular distribution and tissue expression in Arabidopsis. The
present study also provides evidence for the presence of an additional PLD that
is structurally more closely related to PLDgamma than to the other two PLDs.
PMID- 10198097
TI - Identification of a Ca2+/H+ antiport in the plant chloroplast thylakoid membrane
AB - To assess the availability of Ca2+ in the lumen of the thylakoid membrane that is
required to support the assembly of the oxygen-evolving complex of photosystem
II, we have investigated the mechanism of 45Ca2+ transport into the lumen of pea
(Pisum sativum) thylakoid membranes using silicone-oil centrifugation. Trans
thylakoid Ca2+ transport is dependent on light or, in the dark, on exogenously
added ATP. Both light and ATP hydrolysis are coupled to Ca2+ transport through
the formation of a transthylakoid pH gradient. The H+-transporting ionophores
nigericin/K+ and carbonyl cyanide 3-chlorophenylhydrazone inhibit the transport
of Ca2+. Thylakoid membranes are capable of accumulating up to 30 nmol Ca2+ mg-1
chlorophyll from external concentrations of 15 MUM over the course of a 15-min
reaction. These results are consistent with the presence of an active Ca2+/H+
antiport in the thylakoid membrane. Ca2+ transport across the thylakoid membrane
has significant implications for chloroplast and plant Ca2+ homeostasis. We
propose a model of chloroplast Ca2+ regulation whereby the activity of the
Ca2+/H+ antiporter facilitates the light-dependent uptake of Ca2+ by chloroplasts
and reduces stromal Ca2+ levels.
PMID- 10198098
TI - Acclimation of Arabidopsis leaves developing at low temperatures. Increasing
cytoplasmic volume accompanies increased activities of enzymes in the Calvin
cycle and in the sucrose-biosynthesis pathway.
AB - Photosynthetic and metabolic acclimation to low growth temperatures were studied
in Arabidopsis (Heynh.). Plants were grown at 23 degrees C and then shifted to 5
degrees C. We compared the leaves shifted to 5 degrees C for 10 d and the new
leaves developed at 5 degrees C with the control leaves on plants that had been
left at 23 degrees C. Leaf development at 5 degrees C resulted in the recovery of
photosynthesis to rates comparable with those achieved by control leaves at 23
degrees C. There was a shift in the partitioning of carbon from starch and toward
sucrose (Suc) in leaves that developed at 5 degrees C. The recovery of
photosynthetic capacity and the redirection of carbon to Suc in these leaves were
associated with coordinated increases in the activity of several Calvin-cycle
enzymes, even larger increases in the activity of key enzymes for Suc
biosynthesis, and an increase in the phosphate available for metabolism.
Development of leaves at 5 degrees C also led to an increase in cytoplasmic
volume and a decrease in vacuolar volume, which may provide an important
mechanism for increasing the enzymes and metabolites in cold-acclimated leaves.
Understanding the mechanisms underlying such structural changes during leaf
development in the cold could result in novel approaches to increasing plant
yield.
PMID- 10198099
TI - A calcium-selective channel from root-Tip endomembranes of garden cress
AB - A Ca2+ channel from root-tip endomembranes of garden cress (Lepidium sativum L.)
(LCC1) was characterized using the planar lipid-bilayer technique. Investigation
of single-channel recordings revealed that LCC1 is voltage gated and strongly
rectifying. In symmetrical 50 mM CaCl2 solutions, the single-channel conductance
was 24 picosiemens. LCC1 showed a moderate selectivity for Ca2+ over K+ (9.4:1)
and was permeable for a range of divalent cations (Ca2+, Ba2+, and Sr2+). In
contrast to Bryonia dioica Ca2+ channel 1, a Ca2+-selective channel from the
endoplasmic reticulum of touch-sensitive tendrils, LCC1 showed no bursting
channel activity and had a low open probability and mean open time (2.83 ms at 50
mV). Inhibitor studies demonstrated that LCC1 is blocked by micromolar
concentrations of erythrosin B (inhibitor concentration for 50% inhibition [IC50]
= 1. 8 MUM) and the trivalent cations La3+ (IC50 = 5 MUM) and Gd3+ (IC50 = 10
MUM), whereas verapamil showed no blocking effect. LCC1 may play an important
role in the regulation of the cytoplasmic free Ca2+ concentration in root-tip
and/or root-cap cells. The question of whether this ion channel is part of the
gravitropic signal transduction pathway deserves further investigation.
PMID- 10198100
TI - Protective function of chloroplast 2-cysteine peroxiredoxin in photosynthesis.
Evidence from transgenic Arabidopsis.
AB - 2-Cysteine peroxiredoxins (2-CPs) constitute a ubiquitous group of peroxidases
that reduce cell-toxic alkyl hydroperoxides to their corresponding alcohols.
Recently, we cloned 2-CP cDNAs from plants and characterized them as chloroplast
proteins. To elucidate the physiological function of the 2-CP in plant
metabolism, we generated antisense mutants in Arabidopsis. In the mutant lines a
2-CP deficiency developed during early leaf and plant development and eventually
the protein accumulated to wild-type levels. In young mutants with reduced
amounts of 2-CP, photosynthesis was impaired and the levels of D1 protein, the
light-harvesting protein complex associated with photosystem II, chloroplast ATP
synthase, and ribulose-1,5-bisphosphate carboxylase/oxygenase were decreased.
Photoinhibition was particularly pronounced after the application of the protein
synthesis inhibitor, lincomycin. We concluded that the photosynthetic machinery
needs high levels of 2-CP during leaf development to protect it from oxidative
damage and that the damage is reduced by the accumulation of 2-CP protein, by the
de novo synthesis and replacement of damaged proteins, and by the induction of
other antioxidant defenses in 2-CP mutants.
PMID- 10198102
TI - Fluxes of reserve-derived and currently assimilated carbon and nitrogen in
perennial ryegrass recovering from defoliation. The regrowing tiller and its
component functionally distinct zones
AB - The quantitative significance of reserves and current assimilates in regrowing
tillers of severely defoliated plants of perennial ryegrass (Lolium perenne L.)
was assessed by a new approach, comprising 13C/12C and 15N/14N steady-state
labeling and separation of sink and source zones. The functionally distinct zones
showed large differences in the kinetics of currently assimilated C and N. These
are interpreted in terms of "substrate" and "tissue" flux among zones and C and N
turnover within zones. Tillers refoliated rapidly, although C and N supply was
initially decreased. Rapid refoliation was associated with (a) transient
depletion of water-soluble carbohydrates and dilution of structural biomass in
the immature zone of expanding leaves, (b) rapid transition to current
assimilation-derived growth, and (c) rapid reestablishment of a balanced C:N
ratio in growth substrate. This balance (C:N, approximately 8.9 [w/w] in new
biomass) indicated coregulation of growth by C and N supply and resulted from
complementary fluxes of reserve- and current assimilation-derived C and N.
Reserves were the dominant N source until approximately 3 d after defoliation.
Amino-C constituted approximately 60% of the net influx of reserve C during the
first 2 d. Carbohydrate reserves were an insignificant source of C for tiller
growth after d 1. We discuss the physiological mechanisms contributing to
defoliation tolerance.
PMID- 10198101
TI - Characterization of two divergent endo-beta-1,4-glucanase cDNA clones highly
expressed in the nonclimacteric strawberry fruit.
AB - Two cDNAs clones (Cel1 and Cel2) encoding divergent endo-beta-1, 4-glucanases
(EGases) have been isolated from a cDNA library obtained from ripe strawberry
(Fragaria x ananassa Duch) fruit. The analysis of the amino acid sequence
suggests that Cel1 and Cel2 EGases have different secondary and tertiary
structures and that they differ in the presence of potential N-glycosylation
sites. By in vitro translation we show that Cel1 and Cel2 bear a functional
signal peptide, the cleavage of which yields mature proteins of 52 and 60 kD,
respectively. Phylogenetic analysis revealed that the Cel2 EGase diverged early
in evolution from other plant EGases. Northern analysis showed that both EGases
are highly expressed in fruit and that they have different temporal patterns of
accumulation. The Cel2 EGase was expressed in green fruit, accumulating as the
fruit turned from green to white and remaining at an elevated, constant level
throughout fruit ripening. In contrast, the Cel1 transcript was not detected in
green fruit and only a low level of expression was observed in white fruit. The
level of Cel1 mRNA increased gradually during ripening, reaching a maximum in
fully ripe fruit. The high levels of Cel1 and Cel2 mRNA in ripe fruit and their
overlapping patterns of expression suggest that these EGases play an important
role in softening during ripening. In addition, the early expression of Cel2 in
green fruit, well before significant softening begins, suggests that the product
of this gene may also be involved in processes other than fruit softening, e.g.
cell wall expansion.
PMID- 10198103
TI - Arabidopsis Sec21p and Sec23p homologs. Probable coat proteins of plant COP
coated vesicles.
AB - Intracellular protein transport between the endoplasmic reticulum (ER) and the
Golgi apparatus and within the Golgi apparatus is facilitated by COP (coat
protein)-coated vesicles. Their existence in plant cells has not yet been
demonstrated, although the GTP-binding proteins required for coat formation have
been identified. We have generated antisera against glutathione-S-transferase
fusion proteins prepared with cDNAs encoding the Arabidopsis Sec21p and Sec23p
homologs (AtSec21p and AtSec23p, respectively). The former is a constituent of
the COPI vesicle coatomer, and the latter is part of the Sec23/24p dimeric
complex of the COPII vesicle coat. Cauliflower (Brassica oleracea) inflorescence
homogenates were probed with these antibodies and demonstrated the presence of
AtSec21p and AtSec23p antigens in both the cytosol and membrane fractions of the
cell. The membrane-associated forms of both antigens can be solubilized by
treatments typical for extrinsic proteins. The amounts of the cytosolic antigens
relative to the membrane-bound forms increase after cold treatment, and the two
antigens belong to different protein complexes with molecular sizes comparable to
the corresponding nonplant coat proteins. Sucrose-density-gradient centrifugation
of microsomal cell membranes from cauliflower suggests that, although AtSec23p
seems to be preferentially associated with ER membranes, AtSec21p appears to be
bound to both the ER and the Golgi membranes. This could be in agreement with the
notion that COPII vesicles are formed at the ER, whereas COPI vesicles can be
made by both Golgi and ER membranes. Both AtSec21p and AtSec23p antigens were
detected on membranes equilibrating at sucrose densities equivalent to those
typical for in vitro-induced COP vesicles from animal and yeast systems.
Therefore, a further purification of the putative plant COP vesicles was
undertaken.
PMID- 10198104
TI - Characterization of two novel type I ribosome-inactivating proteins from the
storage roots of the andean crop Mirabilis expansa.
AB - Two novel type I ribosome-inactivating proteins (RIPs) were found in the storage
roots of Mirabilis expansa, an underutilized Andean root crop. The two RIPs,
named ME1 and ME2, were purified to homogeneity by ammonium sulfate
precipitation, cation-exchange perfusion chromatography, and C4 reverse-phase
chromatography. The two proteins were found to be similar in size (27 and 27.5
kD) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and their
isoelectric points were determined to be greater than pH 10.0. Amino acid N
terminal sequencing revealed that both ME1 and ME2 had conserved residues
characteristic of RIPs. Amino acid composition and western-blot analysis further
suggested a structural similarity between ME1 and ME2. ME2 showed high similarity
to the Mirabilis jalapa antiviral protein, a type I RIP. Depurination of yeast
26S rRNA by ME1 and ME2 demonstrated their ribosome-inactivating activity.
Because these two proteins were isolated from roots, their antimicrobial activity
was tested against root-rot microorganisms, among others. ME1 and ME2 were active
against several fungi, including Pythium irregulare, Fusarium oxysporum solani,
Alternaria solani, Trichoderma reesei, and Trichoderma harzianum, and an additive
antifungal effect of ME1 and ME2 was observed. Antibacterial activity of both ME1
and ME2 was observed against Pseudomonas syringae, Agrobacterium tumefaciens,
Agrobacterium radiobacter, and others.
PMID- 10198105
TI - Cloning and characterization of a gibberellin-induced RNase expressed in barley
aleurone cells.
AB - We cloned a cDNA for a gibberellin-induced ribonuclease (RNase) expressed in
barley (Hordeum vulgare) aleurone and the gene for a second barley RNase
expressed in leaf tissue. The protein encoded by the cDNA is unique among RNases
described to date in that it contains a novel 23-amino acid insert between the C2
and C3 conserved sequences. Expression of the recombinant protein in tobacco
(Nicotiana tabacum) suspension-cultured protoplasts gave an active RNase of the
expected size, confirming the enzymatic activity of the protein. Analyses of
hormone regulation of expression of mRNA for the aleurone RNase revealed that,
like the pattern for alpha-amylase, mRNA levels increased in the presence of
gibberellic acid, and its antagonist abscisic acid prevented this effect.
Quantitative studies at early times demonstrated that cycloheximide treatment of
aleurone layers increased mRNA levels 4-fold, whereas a combination of
gibberellin plus cycloheximide treatment was required to increase alpha-amylase
mRNA levels to the same extent. These results are consistent with loss of
repression as an initial effect of gibberellic acid on transcription of those
genes, although the regulatory pathways for the two genes may differ.
PMID- 10198106
TI - Slow and prolonged activation of the p47 protein kinase during hypersensitive
cell death in a culture of tobacco cells
AB - To investigate the involvement of protein kinases in the signaling cascade that
leads to hypersensitive cell death, we used a previously established system in
which a fungal elicitor, xylanase from Trichoderma viride (TvX), induces a
hypersensitive reaction in tobacco (Nicotiana tabacum) cells in culture (line
XD6S). The elicitor induced the slow and prolonged activation of a p47 protein
kinase, which has the characteristics of a family member of the mitogen-activated
protein kinases. An inhibitor of protein kinases, staurosporine, and a blocker of
Ca channels, Gd3+ ions, both of which blocked the TvX-induced hypersensitive cell
death, inhibited the TvX-induced activation of p47 protein kinase. Moreover, an
inhibitor of serine/threonine protein phosphatase alone induced both rapid cell
death and the persistent activation of the p47 protein kinase. Thus, the p47
protein kinase might be a component of the signal transduction pathway that leads
to hypersensitive cell death, and the regulation of the duration of activation of
the p47 protein kinase might be important in determining the destiny of tobacco
cells.
PMID- 10198107
TI - A Selaginella lepidophylla trehalose-6-phosphate synthase complements growth and
stress-tolerance defects in a yeast tps1 mutant.
AB - The accumulation of the disaccharide trehalose in anhydrobiotic organisms allows
them to survive severe environmental stress. A plant cDNA, SlTPS1, encoding a 109
kD protein, was isolated from the resurrection plant Selaginella lepidophylla,
which accumulates high levels of trehalose. Protein-sequence comparison showed
that SlTPS1 shares high similarity to trehalose-6-phosphate synthase genes from
prokaryotes and eukaryotes. SlTPS1 mRNA was constitutively expressed in S.
lepidophylla. DNA gel-blot analysis indicated that SlTPS1 is present as a single
copy gene. Transformation of a Saccharomyces cerevisiae tps1Delta mutant
disrupted in the ScTPS1 gene with S. lepidophylla SlTPS1 restored growth on
fermentable sugars and the synthesis of trehalose at high levels. Moreover, the
SlTPS1 gene introduced into the tps1Delta mutant was able to complement both
deficiencies: sensitivity to sublethal heat treatment at 39 degrees C and induced
thermotolerance at 50 degrees C. The osmosensitive phenotype of the yeast
tps1Delta mutant grown in NaCl and sorbitol was also restored by the SlTPS1 gene.
Thus, SlTPS1 protein is a functional plant homolog capable of sustaining
trehalose biosynthesis and could play a major role in stress tolerance in S.
lepidophylla.
PMID- 10198108
TI - Oxidative turnover of soybean root glutamine synthetase. In vitro and in vivo
studies
AB - Glutamine synthetase (GS) is the key enzyme in ammonia assimilation and catalyzes
the ATP-dependent condensation of NH3 with glutamate to produce glutamine. GS in
plants is an octameric enzyme. Recent work from our laboratory suggests that GS
activity in plants may be regulated at the level of protein turnover (S.J.
Temple, T.J. Knight, P.J. Unkefer, C. Sengupta-Gopalan [1993] Mol Gen Genet 236:
315-325; S.J. Temple, S. Kunjibettu, D. Roche, C. Sengupta-Gopalan [1996] Plant
Physiol 112: 1723-1733; S.J. Temple, C. Sengupta-Gopalan [1997] In C.H. Foyer,
W.P. Quick, eds, A Molecular Approach to Primary Metabolism in Higher Plants.
Taylor & Francis, London, pp 155-177). Oxidative modification of GS has been
implicated as the first step in the turnover of GS in bacteria. By incubating
soybean (Glycine max) root extract enriched in GS in a metal-catalyzed oxidation
system to produce the.OH radical, we have shown that GS is oxidized and that
oxidized GS is inactive and more susceptible to degradation than nonoxidized GS.
Histidine and cysteine protect GS from metal-catalyzed inactivation, indicating
that oxidation modifies the GS active site and that cysteine and histidine
residues are the site of modification. Similarly, ATP and particularly
ATP/glutamate give the enzyme the greatest protection against oxidative
inactivation. The roots of plants fed ammonium nitrate showed a 3-fold increase
in the level of GS polypeptides and activity compared with plants not fed
ammonium nitrate but without a corresponding increase in the GS transcript level.
This would suggest either translational or posttranslational control of GS
levels.
PMID- 10198109
TI - Overexpression of Arabidopsis phytochrome B inhibits phytochrome A function in
the presence of sucrose.
AB - Overexpression of phytochrome B (phyB) in Arabidopsis has previously been
demonstrated to result in dominant negative interference of phytochrome A (phyA)
mediated hypocotyl growth inhibition in far-red (FR) light. This phenomenon has
been examined further in this study and has been found to be dependent on the FR
fluence rate and on the availability of metabolizable sugars in the growth
medium. Poorly metabolized sugars capable of activating the putative hexokinase
sensory function were not effective in eliciting the phytochrome interference
response. Overexpressed phyB lacking the chromophore-binding site was also
effective at inhibiting the phyA response, especially at higher fluence rates of
FR. Overexpressed phyB produces the dominant negative phenotype without any
apparent effect on phyA abundance or degradation. It is possible that phyA and
phyB interact with a common reaction partner but that either the energy state of
the cell or a separate sugar-signaling mechanism modulates the phytochrome
signaling interactions.
PMID- 10198110
TI - Characterization and subcellular compartmentation of recombinant 4
hydroxyphenylpyruvate dioxygenase from Arabidopsis in transgenic tobacco.
AB - 4-Hydroxyphenylpyruvate dioxygenase (4HPPD) catalyzes the formation of
homogentisate (2,5-dihydroxyphenylacetate) from p-hydroxyphenylpyruvate and
molecular oxygen. In plants this enzyme activity is involved in two distinct
metabolic processes, the biosynthesis of prenylquinones and the catabolism of
tyrosine. We report here the molecular and biochemical characterization of an
Arabidopsis 4HPPD and the compartmentation of the recombinant protein in
chlorophyllous tissues. We isolated a 1508-bp cDNA with one large open reading
frame of 1338 bp. Southern analysis strongly suggested that this Arabidopsis
4HPPD is encoded by a single-copy gene. We investigated the biochemical
characteristics of this 4HPPD by overproducing the recombinant protein in
Escherichia coli JM105. The subcellular localization of the recombinant 4HPPD in
chlorophyllous tissues was examined by overexpressing its complete coding
sequence in transgenic tobacco (Nicotiana tabacum), using Agrobacterium
tumefaciens transformation. We performed western analyses for the immunodetection
of protein extracts from purified chloroplasts and total leaf extracts and for
the immunocytochemistry on tissue sections. These analyses clearly revealed that
4HPPD was confined to the cytosol compartment, not targeted to the chloroplast.
Western analyses confirmed the presence of a cytosolic form of 4HPPD in cultured
green Arabidopsis cells.
PMID- 10198111
TI - Brassinosteroid/Sterol synthesis and plant growth as affected by lka and lkb
mutations of Pea
AB - The dwarf pea (Pisum sativum) mutants lka and lkb are brassinosteroid (BR)
insensitive and deficient, respectively. The dwarf phenotype of the lkb mutant
was rescued to wild type by exogenous application of brassinolide and its
biosynthetic precursors. Gas chromatography-mass spectrometry analysis of the
endogenous sterols in this mutant revealed that it accumulates 24
methylenecholesterol and isofucosterol but is deficient in their hydrogenated
products, campesterol and sitosterol. Feeding experiments using 2H-labeled 24
methylenecholesterol indicated that the lkb mutant is unable to isomerize and/or
reduce the Delta24(28) double bond. Dwarfism of the lkb mutant is, therefore, due
to BR deficiency caused by blocked synthesis of campesterol from 24
methylenecholesterol. The lkb mutation also disrupted sterol composition of the
membranes, which, in contrast to those of the wild type, contained isofucosterol
as the major sterol and lacked stigmasterol. The lka mutant was not BR deficient,
because it accumulated castasterone. Like some gibberellin-insensitive dwarf
mutants, overproduction of castasterone in the lka mutant may be ascribed to the
lack of a feedback control mechanism due to impaired perception/signal
transduction of BRs. The possibility that castasterone is a biologically active
BR is discussed.
PMID- 10198112
TI - An Arabidopsis GSK3/shaggy-like gene that complements yeast salt stress-sensitive
mutants is induced by NaCl and abscisic acid.
AB - GSK3/shaggy-like genes encode kinases that are involved in a variety of
biological processes. By functional complementation of the yeast calcineurin
mutant strain DHT22-1a with a NaCl stress-sensitive phenotype, we isolated the
Arabidopsis cDNA AtGSK1, which encodes a GSK3/shaggy-like protein kinase. AtGSK1
rescued the yeast calcineurin mutant cells from the effects of high NaCl. Also,
the AtGSK1 gene turned on the transcription of the NaCl stress-inducible PMR2A
gene in the calcineurin mutant cells under NaCl stress. To further define the
role of AtGSK1 in the yeast cells we introduced a deletion mutation at the MCK1
gene, a yeast homolog of GSK3, and examined the phenotype of the mutant. The mck1
mutant exhibited a NaCl stress-sensitive phenotype that was rescued by AtGSK1.
Also, constitutive expression of MCK1 complemented the NaCl-sensitive phenotype
of the calcineurin mutants. Therefore, these results suggest that Mck1p is
involved in the NaCl stress signaling in yeast and that AtGSK1 may functionally
replace Mck1p in the NaCl stress response in the calcineurin mutant. To
investigate the biological function of AtGSK1 in Arabidopsis we examined the
expression of AtGSK1. Northern-blot analysis revealed that the expression is
differentially regulated in various tissues with a high level expression in
flower tissues. In addition, the AtGSK1 expression was induced by NaCl and
exogenously applied ABA but not by KCl. Taken together, these results suggest
that AtGSK1 is involved in the osmotic stress response in Arabidopsis.
PMID- 10198113
TI - Molecular analysis of (R)-(+)-mandelonitrile lyase microheterogeneity in black
cherry.
AB - The flavoprotein (R)-(+)-mandelonitrile lyase (MDL; EC 4.1.2.10), which plays a
key role in cyanogenesis in rosaceous stone fruits, occurs in black cherry
(Prunus serotina Ehrh.) homogenates as several closely related isoforms.
Biochemical and molecular biological methods were used to investigate MDL
microheterogeneity and function in this species. Three novel MDL cDNAs of high
sequence identity (designated MDL2, MDL4, and MDL5) were isolated. Like MDL1 and
MDL3 cDNAs (Z. Hu, J.E. Poulton [1997] Plant Physiol 115: 1359-1369), they had
open reading frames that predicted a flavin adenine dinucleotide-binding site,
multiple N-glycosylation sites, and an N-terminal signal sequence. The N terminus
of an MDL isoform purified from seedlings matched the derived amino acid sequence
of the MDL4 cDNA. Genomic sequences corresponding to the MDL1, MDL2, and MDL4
cDNAs were obtained by polymerase chain reaction amplification of genomic DNA.
Like the previously reported mdl3 gene, these genes are interrupted at identical
positions by three short, conserved introns. Given their overall similarity, we
conclude that the genes mdl1, mdl2, mdl3, mdl4, and mdl5 are derived from a
common ancestral gene and constitute members of a gene family. Genomic Southern
blot analysis showed that this family has approximately eight members. Northern
blot analysis using gene-specific probes revealed differential expression of the
genes mdl1, mdl2, mdl3, mdl4, and mdl5.
PMID- 10198114
TI - A gene encoding a hevein-like protein from elderberry fruits is homologous to PR
4 and class V chitinase genes.
AB - We isolated SN-HLPf (Sambucus nigra hevein-like fruit protein), a hevein-like
chitin-binding protein, from mature elderberry fruits. Cloning of the
corresponding gene demonstrated that SN-HLPf is synthesized as a chimeric
precursor consisting of an N-terminal chitin-binding domain corresponding to the
mature elderberry protein and an unrelated C-terminal domain. Sequence
comparisons indicated that the N-terminal domain of this precursor has high
sequence similarity with the N-terminal domain of class I PR-4 (pathogenesis
related) proteins, whereas the C terminus is most closely related to that of
class V chitinases. On the basis of these sequence homologies the gene encoding
SN-HLPf can be considered a hybrid between a PR-4 and a class V chitinase gene.
PMID- 10198115
TI - Characterization of mutants with alterations of the phosphorylation site in the
D2 photosystem II polypeptide of chlamydomonas reinhardtii
AB - We have changed the potential phosphorylation site, a threonine residue at
position 2 of the D2 polypeptide of the photosystem II complex of Chlamydomonas
reinhardtii, to alanine, valine, aspartate, proline, glycine, or glutamate.
Mutants with neutral amino acid changes did not display any phenotype with regard
to photoautotrophic growth, light sensitivity, fluorescence transients, or
photoinhibition. Pulse labeling of these mutants with 32P indicated that a
phosphorylated protein of the same size as D2 is absent in these mutants,
suggesting that threonine-2 is indeed the unique phosphorylation site of D2. In
contrast, mutants in which threonine-2 has been replaced with acidic residues are
deficient in photosystem II. Use of chimeric genes containing the psbD 5'
untranslated region revealed that the initiation of translation was not affected
in these mutants, but the mutations interfered with a later step of D2 synthesis
and accumulation.
PMID- 10198116
TI - A Group I intron in the nuclear small subunit rRNA gene of Cryptendoxyla
hypophloia, an ascomycetous fungus: evidence for a new major class of Group I
introns.
AB - The ascomycetous fungus Cryptendoxyla hypophloia contains an insertion of 433
base pairs in the genes encoding nuclear small subunit ribosomal RNA. Secondary
structure analyses of the insert reveal characteristics indicative of a Group I
intron, including elements P, Q, R, and S; however, the sequences of these
conserved regions deviate significantly from recognized consensus sequences for
Group I introns. Principal-components analysis, based on 79 nucleotide positions
from the conserved core sequences of 93 Group I introns, identified 17 introns
similar to that of C. hypophloia. This grouping, which includes inserts from
phylogenetically diverse organisms, cannot readily be classified in any
previously recognized major group of Group I introns. We propose the creation of
a new group, IE, to accommodate these sequences, and discuss the evolutionary
relationships between group IE and other major groups of Group I introns.
PMID- 10198117
TI - Positional dependence, cliques, and predictive motifs in the bHLH protein domain.
AB - Quantitative analyses were carried out on a large number of proteins that contain
the highly conserved basic helix-loop-helix domain. Measures derived from
information theory were used to examine the extent of conservation at amino acid
sites within the bHLH domain as well as the extent of mutual information among
sites within the domain. Using the Boltzmann entropy measure, we described the
extent of amino acid conservation throughout the bHLH domain. We used position
association (pa) statistics that reflect the joint probability of occurrence of
events to estimate the "mutual information content" among distinct amino acid
sites. Further, we used pa statistics to estimate the extent of association in
amino acid composition at each site in the domain and between amino acid
composition and variables reflecting clade and group membership, loop length, and
the presence of a leucine zipper. The pa values were also used to describe groups
of amino acid sites called "cliques" that were highly associated with each other.
Finally, a predictive motif was constructed that accurately identifies bHLH
domain-containing proteins that belong to Groups A and B.
PMID- 10198118
TI - Diversification pattern of the HMG and SOX family members during evolution.
AB - From a database containing the published HMG protein sequences, we constructed an
alignment of the HMG box functional domain based on sequence identity. Due to the
large number of sequences (more than 250) and the short size of this domain,
several data sets were used. This analysis reveals that the HMG box superfamily
can be separated into two clearly defined subfamilies: (i) the SOX/MATA/TCF
family, which clusters proteins able to bind to specific DNA sequences; and (ii)
the HMG/UBF family, which clusters members which bind non specifically to DNA.
The appearance and diversification of these subfamilies largely predate the split
between the yeast and the metazoan lineages. Particular emphasis was placed on
the analysis of the SOX subfamily. For the first time our analysis clearly
identified the SOX subfamily as structured in six groups of genes named SOX5/6,
SRY, SOX2/3, SOX14, SOX4/22, and SOX9/18. The validity of these gene clusters is
confirmed by their functional characteristics and their sequences outside the HMG
box. In sharp contrast, there are only a few robust branching patterns inside the
UBF/HMG family, probably because of the much more ancient diversification of this
family than the diversification of the SOX family. The only consistent groups
that can be detected by our analysis are HMG box 1, vertebrate HMG box 2, insect
SSRP, and plant HMG. The various UBF boxes cannot be clustered together and their
diversification appears to be extremely ancient, probably before the appearance
of metazoans.
PMID- 10198119
TI - RNA polymerase of Aquifex pyrophilus: implications for the evolution of the
bacterial rpoBC operon and extremely thermophilic bacteria.
AB - A 16,226-bp fragment from the genome of Aquifex pyrophilus was sequenced,
containing the genes for ribosomal proteins L1, L10, and L7/12 (rplAJL), DNA
directed RNA polymerase subunits beta and beta' (rpoBC), alanyl-tRNA synthetase
(alaS), and subunit A of proteinase Clp (clpA). Enzymatic activity and extreme
thermostability of purified A. pyrophilus RNA polymerase were verified.
Transcription initiation on a DNA construct harboring the T7 A1 promoter was
demonstrated by elongation of a 32P-labeled trinucleotide. Phylogenetic analyses
of the two largest subunits of bacterial RNA polymerases (beta and beta') showed
overall consistency with the 16S rRNA-based phylogeny, except for the positions
of the hyperthermophiles A. pyrophilus and Thermotoga maritima and for the
location of the root of the domain Bacteria. In the phylogenies for both RNA
polymerase subunits beta and beta', A. pyrophilus was placed within the Gram
negative bacteria below the epsilon subdivision of the Proteobacteria. No support
was found for the 16S rRNA-based hypothesis that A. pyrophilus might be the
deepest branch of the Bacteria, but the cell wall-less mycoplasmas were found
with a high confidence at the root of the Bacteria phylogenies. This raised
doubts not only about whether the original Bacteria were indeed like the
hyperthermophiles, but also concerning the value of single-gene phylogenies for
hypotheses about the evolution of organisms.
PMID- 10198120
TI - Partial sequence of a sponge mitochondrial genome reveals sequence similarity to
Cnidaria in cytochrome oxidase subunit II and the large ribosomal RNA subunit.
AB - A 2550-bp portion of the mitochondrial genome of a Demosponge, genus Tetilla, was
amplified from whole genomic DNA extract and sequenced. The sequence was found to
code for the 3' end of the 16S rRNA gene, cytochrome c oxidase subunit II, a
lysine tRNA, ATPase subunit 8, and a 5' portion of ATPase subunit 6. The Porifera
cluster distinctly within the eumetazoan radiation, as a sister group to the
Cnidaria. Also, the mitochondrial genetic code of this sponge is likely identical
to that found in the Cnidaria. Both the full COII DNA and protein sequences and a
portion of the 16S rRNA gene were found to possess a striking similarity to
published Cnidarian mtDNA sequences, allying the Porifera more closely to the
Cnidaria than to any other metazoan phylum. The gene arrangement, COII-tRNALys
ATP8-ATP6, is observed in many Eumetazoan phyla and is apparently ancestral in
the metazoa.
PMID- 10198121
TI - Gene duplication and gene conversion in the Caenorhabditis elegans genome.
AB - A comprehensive analysis of duplication and gene conversion for 7394
Caenorhabditis elegans genes (about half the expected total for the genome) is
presented. Of the genes examined, 40% are involved in duplicated gene pairs.
Intrachromosomal or cis gene duplications occur approximately two times more
often than expected. In general the closer the members of duplicated gene pairs
are, the more likely it is that gene orientation is conserved. Gene conversion
events are detectable between only 2% of the duplicated pairs. Even given the
excesses of cis duplications, there is an excess of gene conversion events
between cis duplicated pairs on every chromosome except the X chromosome. The
relative rates of cis and trans gene conversion and the negative correlation
between conversion frequency and DNA sequence divergence for unconverted regions
of converted pairs are consistent with previous experimental studies in yeast.
Three recent, regional duplications, each spanning three genes are described. All
three have already undergone substantial deletions spanning hundreds of base
pairs. The relative rates of duplication and deletion may contribute to the
compactness of the C. elegans genome.
PMID- 10198122
TI - Phylogenies of developmentally important proteins do not support the hypothesis
of two rounds of genome duplication early in vertebrate history.
AB - It has been proposed that two rounds of duplication of the entire genome
(polyploidization) occurred early in vertebrate history (the 2R hypothesis); and
the observation that certain gene families important in regulating development
have four members in vertebrates, as opposed to one in Drosophila, has been
adduced as evidence in support of this hypothesis. However, such a pattern of
relationship can be taken as support of the 2R hypothesis only if (1) the four
vertebrate genes can be shown to have diverged after the origin of vertebrates,
and (2) the phylogeny of the four vertebrate genes (A-D) exhibits a topology of
the form (AB) (CD), rather than (A) (BCD). In order to test the 2R hypothesis, I
constructed phylogenies for nine protein families important in development. Only
one showed a topology of the form (AB) (CD), and that received weak statistical
support. In contrast, four phylogenies showed topologies of the form (A) (BCD)
with statistically significant support. Furthermore, in two cases there was
significant support for duplication of the vertebrate genes prior to the
divergence of deuterostomes and protostomes: in one case there was significant
support for duplication of the vertebrate genes at least prior to the divergence
of vertebrates and urochordates, and in one case there was weak support for
duplication of the vertebrate genes prior to the divergence of deuterostomes and
protostomes. Taken together with other recently published phylogenies of
developmentally important genes, these results provide strong evidence against
the 2R hypothesis.
PMID- 10198123
TI - A novel tripartite structure comprising a mariner-like element and two additional
retrotransposons found in the Bombyx mori genome.
AB - A clone of a DNA-mediated mobile element (transposon) corresponding to a mariner
like element (MLE) was obtained by carrying out the polymerase chain reaction
with genomic DNA of Bombyx mori using a Hyalophora cecropia MLE sequence as a
primer. This clone had a size of about 4.2 kb and, after sequencing, was found to
contain an RNA-mediated, shorter retrotransposon named L1Bm, which was in turn
integrated with a much longer retrotransposon named BMC1. Thus, the mobile
elements made a novel tripartite structure. The BMC1 and L1Bm moieties of the
composite structure each contained a 63-bp conserved sequence which was
subsequently found to be highly conserved in all BMC1 and L1Bm elements
registered so far. We propose that the 63-bp stretch may be a recognition site
for a retrotransposition mechanism conducted by a reverse transcriptase and an
endonuclease complex. On the basis of this inference, we propose a model that
predicts how different types of BMC1 and L1Bm elements are dispersed in the
genome. In addition, a phylogenetic tree made from the current and extant BMC1
and L1Bm sequences indicated that these elements can be classified into
Subfamilies I and II.
PMID- 10198124
TI - Contributions to the phylogeny of the Cyclophyllidea (Cestoda) inferred from
mitochondrial 12S rDNA.
AB - A 314-bp fragment of the mitochondrial 12S rRNA gene from 21 cestodes species of
eight families was synthesized by PCR with specially designed primers. These
allowed amplification of parasite DNA without concomitant synthesis of host DNA.
Phylogenetic trees were inferred from the sequence data using three methods
(maximum parsimony, maximum likelihood, and Fitch-Margoliash). At the major nodes
all three trees were similar. For the first time the genus Mesocestoides could be
arranged into the Cyclophyllidea and a narrow relationship between the
Mesocestoididae, Taeniidae, Hymenolepididae, Anoplocephalidae, and Dipylidiidae
was shown. Members of the families Catenotaeniidae and a cluster of two families
(Hymenolepididae and Dilepididae) form two monophyletic groups which derive prior
to the remaining families of this phylogenetic study. A third and a fourth clear
monophyletic group were formed by the Taeniidae and by the Mesocestoididae. A
high degree of variation within the examined 304-bp fragment was observed between
two isolates of Taenia taeniaeformis, supporting often discussed genetic
heterogeneity within this species. In contrast, only one nucleotide exchange was
found in 23 isolates of Echinococcus multilocularis of various geographic origin,
indicating that this species is genetically homogenous.
PMID- 10198126
TI - Phylogenetic relationships of orders within the class colpodea (Phylum
ciliophora) inferred from small subunit rRNA gene sequences
AB - Molecular analyses have been used recently to refine our knowledge of
phylogenetic relationships within the ciliated protozoa (phylum Ciliophora). A
current Hennigian phylogeny of the orders in the class Colpodea, based on light
and electron microscopic analyses, makes three important assumptions with regard
to apomorphic character states, namely, (1) that the kreyellid silver line
evolved early in colpodean phylogeny, separating bryometopids, such as
Bryometopus, from all other colpodeans; (2) that the macro-micronuclear complex
is an autapomorphy of the cyrtolophosidids, such as Platyophrya; and (3) that
merotelokinetal stomatogenesis is an apomorphic character of colpodids, such as
Colpoda, Bresslaua, and Pseudoplatyophrya. These predictions of relationships
within the class Colpodea were investigated by determining the complete small
subunit rRNA gene sequences for the colpodid Bresslaua vorax, the
grossglockneriid Pseudoplatyophrya nana, and the cyrtolophosidid Platyophrya
vorax and a partial sequence for the bryometopid Bryometopus sphagni. These
sequences were combined with the previously published complete SSrRNA sequences
for the colpodid Colpoda inflata and the bursariomorphid Bursaria truncatella.
The affiliations were assessed using both distance matrix and maximum-parsimony
analyses. The tree topologies for the class Colpodea were identical in all
analyses, with bootstrap support for bifurcations always exceeding 60%. The
results suggest the following. (1) Since the clade including Bryometopus and its
sister taxon, Bursaria, is never basal, the kreyellid silver-line system evolved
later in colpodean phylogeny and does not separate bryometopids from all other
colpodeans. (2) Since Platyophrya is always the sister taxon to the other five
genera, there is a fundamental phylogenetic significance for its macro
micronuclear complex. (3) Since the colpodids, Colpoda, Bresslaua, and
Pseudoplatyophrya, always group in one clade, merotelokinetal stomatogenesis
appears to be a derived character state.
PMID- 10198125
TI - Rates of nucleotide substitution in angiosperm mitochondrial DNA sequences and
dates of divergence between Brassica and other angiosperm lineages.
AB - We obtained 16 nucleotide sequences ( approximately 1400 bp each) of the first
intron of the mitochondrial (mt) gene for NADH subunit 4 (nad4) from 10 species
of Brassicaceae. Using these new sequences and five published sequences from
GenBank, we constructed a phylogenetic tree of the Brassicaceae species under
study and showed that the rate of nucleotide substitution in the first intron of
nad4 is very low, about 0.16-0.23 x 10(-9) substitution per site per year, which
is about half of the silent rate in exons of nad4. The ratios of substitution
rates in this intron, ITS, and IGS are approximately 1:23:73, where ITS is the
nuclear intergenic spacer between 18S and 25S rRNA genes and IGS is the
intergenic spacer of 5S rRNA genes. A segment (335 bp) in the first intron of
nad4 in Brassicaceae species that is absent in wheat was considered as a
nonfunctional sequence and used to estimate the neutral rate (the rate of
mutation) in mtDNA to be 0.5-0.7 x 10(-9) substitution per site per year, which
is about three times higher than the substitution rate in the rest of the first
intron of nad4. We estimated that the dates of divergence are 170-235 million
years (Myr) for the monocot-dicot split, 112-156 Myr for the Brassicaceae-Lettuce
split, 14.5-20.4 Myr for the Brassica-Arabidopsis split, and 14.5-20.4 Myr for
the Arabidopsis-Arabideae split.
PMID- 10198127
TI - Multiple origins of cyclodiene insecticide resistance in Tribolium castaneum
(Coleoptera: Tenebrionidae).
AB - The number of origins of pesticide resistance-associated mutations is important
not only to our understanding of the evolution of resistance but also in modeling
its spread. Previous studies of amplified esterase genes in a highly dispersive
Culex mosquito have suggested that insecticide resistance-associated mutations
(specifically a single-gene duplication event) can occur a single time and then
spread throughout global populations. In order to provide data for resistance
associated point mutations, which are more typical of pesticide mechanisms as a
whole, we studied the number of independent origins of cyclodiene insecticide
resistance in the red flour beetle Tribolium castaneum. Target-site insensitivity
to cyclodienes is conferred by single point mutations in the gene Resistance to
dieldrin (Rdl), which codes for a subunit of a gamma-aminobutyric acid (GABA)
receptor. These point mutations are associated with replacements of alanine 302
which render the receptor insensitive to block by the insecticide. We collected
141 strains of Tribolium worldwide and screened them for resistance. Twenty-four
strains contained resistant individuals. After homozygosing 23 of these
resistance alleles we derived a nucleotide sequence phylogeny of the resistant
strains from a 694-bp section of Rdl, encompassing exon 7 (which contains the
resistance-associated mutation) and part of a flanking intron. The phylogeny also
included six susceptible alleles chosen at random from a range of geographical
locations. Resistance alleles fell into six clades and three clades contained
both resistant and susceptible alleles. Although statistical analysis provided
support at only the 5-6% level, the pattern of variation in resistance alleles is
more readily explained by multiple independent origins of resistance than by
spread of a single resistance-associated mutation. For example, two resistance
alleles differed from two susceptible alleles only by the resistance-associated
mutation itself, suggesting that they form the susceptible ancestors and that
resistance arose independently in several susceptible backgrounds. This suggests
that in Tribolium Rdl, de novo mutations for resistance have arisen independently
in several populations. Identical alleles were found in geographically distant
regions as well, also implying that some Rdl alleles have been exported in stored
grain. These differences from the Culex study may stem both from differences in
the population genetics of Tribolium versus that of mosquitoes and differences in
mutation rates associated with point mutations versus gene duplication events.
The Tribolium data therefore suggest that multiple origins of insecticide
resistance (associated with specific point mutations) may be more common than the
spread of single events. These findings have implications for the way in which we
model the evolution and spread of insecticide resistance genes and also suggest
that parallel adaptive substitutions may not be uncommon in phyletic evolution.
PMID- 10198128
TI - Identification of protein-tyrosine phosphatases in Archaea.
AB - Protein-tyrosine dephosphorylation is a major mechanism in cellular regulation. A
large number of protein-tyrosine phosphatases is known from Eukarya, and more
recently bacterial homologues have also been identified. By employing conserved
sequence patterns from both eukaryotic and bacterial protein-tyrosine
phosphatases, we have identified three homologous sequences in two of the four
complete archaeal genomes. Two hypothetical open reading frames in the genome of
Methanococcus jannaschii (MJ0215 and MJECL20) and one in the genome of Pyrococcus
horikoshii (PH1732) clearly bear all the conserved residues of this family. No
homologues were found in the genomes of Archaeoglobus fulgidus and
Methanobacterium thermoautotrophicum. This is the first report of protein
tyrosine phosphatase sequences in Archaea.
PMID- 10198129
TI - The effects of social structure, geographical structure, and population size on
the evolution of mitochondrial DNA: II. Molecular clocks and the lineage sorting
period
PMID- 10198130
TI - Neural basis of endogenous and exogenous spatial orienting. A functional MRI
study.
AB - Whole-brain functional magnetic resonance imaging (MRI) was used to examine the
neural substrates of internally (endogenous) and externally (exogenous) induced
covert shifts of attention. Thirteen normal subjects performed three orienting
conditions: endogenous (location of peripheral target predicted by a central
arrow 80% of the time), exogenous (peripheral target preceded by noninformative
central cue). Behavioral results indicated faster reaction times (RTs) for valid
than for invalid trials for the endogenous condition but slower RTs for valid
than for invalid trials for the exogenous condition (inhibition of return). The
spatial extent and intensity of activation was greatest for the endogenous
condition, consistent with the hypothesis that endogenous orienting is more
effortful (less automatic) than exogenous orienting. Overall, we did not observe
distinctly separable neural systems associated with the endogenous and exogenous
orienting conditions. Both exogenous and endogenous orienting, but not the
control condition, activated bilateral parietal and dorsal premotor regions,
including the frontal eye fields. These results suggest a specific role for these
regions in preparatory responding to peripheral stimuli. The right dorsolateral
prefrontal cortex (BA 46) was activated selectively by the endogenous condition.
This finding suggests that voluntary, but not reflexive, shifts of attention
engage working memory systems.
PMID- 10198131
TI - Categorical and metric spatial processes distinguished by task demands and
practice.
AB - In this study we examined Kosslyn's (1987) claim that the right hemisphere
exhibits a relative superiority for processing metric spatial relations, whereas
the left hemisphere exhibits a relative superiority for processing categorical
spatial relations. In particular, we examined whether some failures to observe
strong visual field (VF) advantages in previous studies might be due to practice
effects that allowed individuals to process tasks in alternative manners (e.g.,
to process a metric task using a categorical strategy). We used two versions of a
task previously employed by Hellige and Michimata (1989)in which individuals
judge the metric (distance) or categorical (above/below) spatial relations
between a bar and a dot. In one version, the position of the bar was held static.
In another, the bar's position varied. This manipulation prevented participants
from using the computer screen as a reference frame, forcing them to compute the
spatial relationships on the basis of the relevant items only (i.e., the bar and
the dot). In the latter, but not the former version of the task we obtained
evidence supporting Kosslyn's hypothesis, namely, a significant right visual
field (RVF) advantage for categorical spatial processing and a trend toward a
left visual field (LVF) advantage for metric spatial processing. Furthermore, the
pattern of results for trials on which information was presented centrally (CVF
trials) was similar to that observed on RVF trials, whereas the pattern for
trials in which identical information was presented in each visual field (BVF
trials) was similar to that observed on LVF trials. Such a pattern is consistent
with Kosslyn's suggestion that categorical processing is better suited for cells
with small receptive fields and metric processing for cells with larger receptive
fields.
PMID- 10198132
TI - A neural network model of lateralization during letter identification.
AB - The causes of cerebral lateralization of cognitive and other functions are
currently not well understood. To investigate one aspect of function
lateralization, a bihemispheric neural network model for a simple visual
identification task was developed that has two parallel interacting paths of
information processing. The model is based on commonly accepted concepts
concerning neural connectivity, activity dynamics, and synaptic plasticity. A
combination of both unsupervised (Hebbian) and supervised (Widrow-Hoff) learning
rules is used to train the model to identify a small set of letters presented as
input stimuli in the left visual hemifield, in the central position, and in the
right visual hemifield. Each visual hemifield projects onto the contralateral
hemisphere, and the two hemispheres interact via a simulated corpus callosum. The
contribution of each individual hemisphere to the process of input stimuli
identification was studied for a variety of underlying asymmetries. The results
indicate that multiple asymmetries may cause lateralization. Lateralization
occurred toward the side having larger size, higher excitability, or higher
learning rate parameters. It appeared more intensively with strong inhibitory
callosal connections, supporting the hypothesis that the corpus callosum plays a
functionally inhibitory role. The model demonstrates clearly the dependence of
lateralization on different hemisphere parameters and suggests that computational
models can be useful in better understanding the mechanisms underlying emergence
of lateralization.
PMID- 10198133
TI - Sleep-induced changes in associative memory.
AB - The notion that dreaming might alter the strength of associative links in memory
was first proposed almost 200 years ago. But no strong evidence of such altered
associative links has been obtained. Semantic priming can be used to quantify the
strength of associative links between pairs of words; it is thought to measure
the automatic spread of activation from a "node" representing one word to nodes
representing semantically related words. Semantic priming could thus be used to
test for global alterations in the strengths of associative links across the wake
sleep cycle. Awakenings from REM and nonREM (NREM) sleep produce a period of
state carry-over during which performance is altered as a result of the brain's
slow transition to full wakefulness, and cognitive testing in this period can
provide information about the functioning of the brain during the prior sleep
period. When subjects were tested across the night--before and after a night's
sleep as well as immediately following forced awakenings from REM and NREM sleep-
weak priming (e. g., thief-wrong) was found to be state dependent (p = 0.016),
whereas strong priming (e.g., hot-cold) was not (p = 0.89). Weak primes were most
effective in the presleep and REM sleep conditions and least effective in NREM
and postsleep conditions. Most striking are analyses comparing weak and strong
priming within each wake-sleep state. Contrary to the normal pattern of priming,
subjects awakened from REM sleep showed greater priming by weak primes than by
strong primes (p = 0.01). This result was seen in each of three protocols. In
contrast, strong priming exceeded weak priming in NREM sleep. The shift in weak
priming seen after REM sleep awakenings suggests that cognition during REM sleep
is qualitatively different from that of waking and NREM sleep and may reflect a
shift in associative memory systems, a shift that we hypothesize underlies the
bizarre and hyperassociative character of REM-sleep dreaming. Known changes in
brainstem activity that control the transition into and maintenance of REM sleep
provide a possible explanation of this shift.
PMID- 10198134
TI - Electrophysiological evidence for two steps in syntactic analysis. Early
automatic and late controlled processes.
AB - In this study we examined the properties of the processes involved in the
structural analysis of sentences using event-related brain potential measures
(ERP). Previous research had shown two ERP components to correlate with phrase
structure violations: an early left anterior negativity (ELAN), which is assumed
to reflect first-pass parsing processes, and a late parietally distributed
positivity (P600), assumed to reflect second-pass parsing processes. We
hypothesized that the first-pass parsing processes are highly automatic, whereas
second-pass parsing processes are more controlled. To test this hypothesis we
varied the proportion of correct sentences and sentences containing phrase
structure violations with incorrect sentences being either of a low (20%
violation) or a high (80% violation) proportion. Results showed that the early
left anterior negativity was elicited and equally pronounced under both
proportion conditions. By contrast, the late positivity was elicited for a low
proportion of incorrect sentences only. This data pattern suggests that first
pass parsing processes are automatic, whereas second-pass parsing processes are
under participants' strategic control.
PMID- 10198135
TI - Saccadic performance as a function of the presence and disappearance of auditory
and visual fixation stimuli.
AB - Relative to when a fixated stimulus remains visible, saccadic latencies are
facilitated when a fixated stimulus is extinguished simultaneously with or prior
to the appearance of an eccentric auditory, visual, or combined visual-auditory
target. In a study of nine human subjects, we determined whether such
facilitation (the "gap effect") occurs equivalently for the disappearance of
fixated auditory stimuli and fixated visual stimuli. In the present study, a
fixated auditory (noise) stimulus remained present (overlap) or else was
extinguished simultaneously with (step) or 200 msec prior to (gap) the appearance
of a visual, auditory (tone), or combined visual-auditory target 10 degrees to
the left or right of fixation. The results demonstrated equivalent facilitatory
effects due to the disappearance of fixated auditory and visual stimuli and are
consistent with the presumed role of the superior colliculus in the gap effect.
PMID- 10198136
TI - Spatial S-R compatibility with centrally presented stimuli. An event-related
asymmetry study on dimensional overlap.
AB - Lateral presentation of relevant information facilitates manual responses if the
side of relevant information corresponds to the side of the response. Recently,
temporally overlapping EEG asymmetries over the central motor cortex and
posterior sites were reported as a possible correlate of the sensory-motor
integration of spatial information. The present study investigated whether
sensory-motor integration of spatial information can occur with symbolic spatial
information the same way as with laterally presented stimuli. The task required
participants to respond to arrows (target stimuli), which were "flanked" (from
above and below) by neutral stimuli or by other arrows (compatible or not). In
Experiment 1, this task was compared to the same task with letters as stimuli and
to an incompatible task where participants had to respond "against" the arrow
direction. The effect of the flankers on response times was largest if subjects
had to respond to the arrows in the common way. This was also the only task of
Experiment 1 for which marked EEG asymmetries related to the direction of the
flankers were observed. In Experiment 2, the onsets of target stimulus and
flankers differed in time. Event-related lateralizations of the EEG over sensory
and primary motor areas--as a lateralized readiness potential--were always,
apparently automatically, evoked by flanking arrows, indicating automatic
response activation evoked by symbolic spatial information. In accordance to
recent theories of temporally decaying response activation, manual responses were
affected only if the target was either shortly preceded by or appeared
simultaneously with the flankers. The temporal overlap of EEG asymmetries related
to direction encoding, automatic response activation, and to response preparation
indicated that a widespread cortical network is activated by a salient
directional information that enables subjects to respond quickly if the
directional code of the stimulus overlaps with the directional code of the
response.
PMID- 10198137
TI - Interview with John Kaas.
AB - Jon Kaas received a Ph.D. in Psychology with Irving Diamond at Duke University
and completed a postdoctoral fellowship with Clinton Woolsey in neurophysiology
at the University of Wisconsin, where he also collaborated with Ray Guillery.
After 4 years as an Assistant Professor in Neurophysiology at Wisconsin, he moved
to the Department of Psychology at Vanderbilt University where he is currently
Centennial Professor. Awards include the Earl Sutherland Prize, Javits
Neuroscience Investigator Award, Krieg Cortical Discoverer Award, and American
Psychological Association Distinguished Scientific Contribution Award.
PMID- 10198138
TI - Motor unit double discharges: statistical anomaly or functional entity?
AB - Motor unit double discharges, or doublets, have been described as two consecutive
motor unit discharges that occur with a short interspike interval of 2.5 - 20 ms
(Simpson, 1969). Double discharges have been reported in the literature for over
70 years. For instance, Eccles and Hoff (1932) found that double discharges were
elicited occasionally at the onset of a crossed extension reflex in the soleus
muscle of the anaesthetized cat. With the use of electrical stimulation
protocols, short interspike intervals inserted at the beginning of a stimulation
train have been shown to increase both the peak force and rate of rise of force
production, and also decrease the range of fatigue. The extent to which double
discharges occur in naturally-occurring voluntary behaviours remains relatively
unexplored. This review examines the issue of whether double discharges occur
solely because of an intrinsic property of motoneurones, thereby representing a
"statistical anomaly," or whether they may result from a neural control strategy
to augment force production, i.e., a "functional entity."
PMID- 10198139
TI - Gender differences in cardiovascular and catecholamine responses to cold-air
exposure at rest.
AB - Metabolic and cardiovascular responses were examined in 8 men and 9 women during
2 hrs of sitting at rest in 5 degrees C. The men and women had similar body
fatness and both groups responded with similar changes relative to control in
cardiac output, blood pressure, total peripheral resistance, VO2, respiratory
exchange ratio, and rectal temperature. However, greater increases in stroke
volume and decreases in heart rate and skin temperature were observed in men
compared to women (p < 0.05). The contribution of CHO and fat to the total energy
expended differed (p < 0.05) between genders; the CHO:fat ratio was 47:53 in men
and 36:64 in women. No gender differences could be observed in plasma
catecholamines. It is concluded that there are striking cardiovascular and
metabolic gender differences in response to cold stress which cannot be accounted
for by body fatness or catecholamine responses.
PMID- 10198140
TI - Exercise in the heat: limitations to performance and the impact of fluid
replacement strategies. Introduction to the symposium.
AB - The cause of fatigue during prolonged exercise in the heat has not been clearly
established, but performance appears to be limited by thermoregulatory and fluid
balance factors. Both dehydration and hyperthermia separately impair performance.
Prior acclimation reduces the impact of heat, and ingestion of fluids also
improves performance. Ingested fluids should contain carbohydrate and some
electrolytes, primarily sodium, but many factors will dictate the choice of
fluids. These include the relative need for carbohydrate to supplement endogenous
stores, the need for fluid replacement, the limitations on replacement imposed by
the nature of the event, and the athlete's own requirements and preferences.
PMID- 10198141
TI - Exercise in the heat: thermoregulatory limitations to performance in humans and
horses.
AB - This paper reviews the limits to exercise imposed by increases in ambient,
hypothalamic, and contracting skeletal muscle temperature in humans and horses.
Like humans, horses frequently compete in hot environments, yet their high mass
specific rate of heat production and low mass-specific surface area for heat
dissipation places them at a great disadvantage compared to humans. Exercise in
hot conditions increases the rate of body heat storage and reduces the time
required to reach a critical hypothalamic temperature that results in voluntary
fatigue. This critical temperature appears to be associated with dysfunction of
the brain's motor control centres. The ensuing voluntary cessation of exercise
appears to coincide with temperature-induced alterations in skeletal muscle
function with increased requirement for anaerobic ATP provision. The duration of
exercise that can be performed before this critical temperature is reached can be
increased by ingesting fluids, of a volume at least equal to that lost in sweat,
within 60 min prior to and during exercise. Emerging research in the area of
skeletal muscle heat dissipative mechanisms involves heat-induced increases in
muscle sympathetic nerve activity, producing stimulation of CIII and CIV afferent
nerve stimulation, and heat-induced release of nitric oxide within skeletal
muscle and skin, producing muscle and skin vasodilation.
PMID- 10198142
TI - Effects of dehydration on exercise performance.
AB - Dehydration refers both to hypohydration (dehydration induced prior to exercise)
and to exercise-induced dehydration (dehydration that develops during exercise).
The latter reduces aerobic endurance performance and results in increased body
temperature, heart rate, perceived exertion, and possibly increased reliance on
carbohydrate as a fuel source. Although the negative effects of exercise-induced
dehydration on exercise performance were clearly demonstrated in the 1940s,
athletes continued to believe for years thereafter that fluid intake was not
beneficial. More recently, negative effects on performance have been demonstrated
with modest (<2%) dehydration, and these effects are exacerbated when the
exercise is performed in a hot environment. The effects of hypohydration may
vary, depending on whether it is induced through diuretics or sauna exposure,
which substantially reduce plasma volume, or prior exercise, which has much less
impact on plasma volume. Hypohydration reduces aerobic endurance, but its effects
on muscle strength and endurance are not consistent and require further study.
PMID- 10198143
TI - Limitations to fluid replacement during exercise.
AB - Fluid replacement during exercise is essential for endurance exercise performance
and reducing the risk of heat illness. Fluids supply water, which ameliorates
dehydration, and also substrate for the working muscles. Absorption of water and
nutrients occurs in the upper part of the small intestine, and replacement may be
limited by the rate at which fluid is emptied from the stomach or absorbed in the
intestine. Gastric emptying of liquids is influenced primarily by the volume of
fluid in the stomach and by its energy density. Increasing the volume will speed
emptying, but increasing the nutrient content will slow emptying. Osmolality,
temperature, and pH of drinks, as well as exercise intensity, are of minor
importance. Intestinal water absorption is a passive process: water follows
osmotic gradients but will also follow the active absorption of nutrients,
especially glucose, which is actively co-transported with sodium. Water transport
is maximised by the presence in the intestine of hypotonic solutions of glucose
and sodium. Hypertonic solutions promote net water secretion into the intestinal
lumen, resulting in a temporary net loss of water from the body. The amount of
fluid ingested by athletes is normally much less than can be tolerated, therefore
issues such as palatability and practising drinking during training are
important.
PMID- 10198144
TI - Dehydration, rehydration, and exercise in the heat: rehydration strategies for
athletic competition.
AB - Exercise capacity and exercise performance are reduced when the ambient
temperature is high. This has mainly been attributed to the large sweat losses
which lead to hypohydration, a failure of thermoregulation, and eventually
circulatory collapse. Exercising athletes rarely drink enough before or during
exercise to replace the ongoing fluid losses, especially in hot conditions. In
order to combat dehydration, hyperthermia, and impending circulatory collapse,
athletes should drink fluids before, during, and after exercise. Preexercise
strategies include attempts to maintain euhydration but also to hyperhydrate.
Hyperhydration is relatively easy to achieve, but thermoregulatory benefits
during prolonged exercise have not been observed in comparison to euhydration. In
prolonged continuous exercise, fluid and carbohydrate (CHO) ingestion has clearly
been shown to improve performance, but the evidence is not so clear for high
intensity intermittent exercise over a prolonged period. The general consensus is
that fluid ingestion should match sweat losses during exercise and that the drink
should contain CHO and electrolytes to assist water transport in the intestine
and to improve palatability. Postexercise rehydration is essential when the
strategies adopted before or during exercise have not been effective. The best
postexercise rehydration strategy would be to ingest a large volume of a beverage
that contains a CHO source and a high sodium content.
PMID- 10198145
TI - Bernstein's heritage. Discovering the right questions in motor control: movements
(1929).
PMID- 10198146
TI - Reflex activation patterns in relation to multidirectional ankle torque in
decerebrate cats.
AB - Cutaneous reflexes have been described primarily according to their actions in
the flexion/extension plane. It is shown here, by measuring electromyography and
isometric force in decerebrate cats, that ankle muscles are activated in relation
to their actions in the abduction/adduction plane during sural nerve (SNR) and
crossed-extension (XER) reflexes. Ankle adductors (tibialis posterior, extensor
digitorum longus, and flexors digitorum and hallucis longus) were active in XER,
but not in SNR. Muscles producing ankle abduction (medial and lateral
gastrocnemii and peroneus longus and brevis) were consistently more strongly
activated in SNR than in XER. This differential pattern of muscle activation
results in greater abduction torque at the ankle in SNR than in XER. These data
demonstrate reflex organization in relation to the multidirectional torque
generated by individual muscles.
PMID- 10198147
TI - The stretch reflex and H-reflex of the human soleus muscle during walking.
AB - Due to the complexity of applying a well-defined stretch during human walking,
most of our knowledge about the short latency stretch reflex modulation in humans
is based on H-reflex studies. To illuminate the difference between the two
methodologies, both types of reflexes were evoked in the same subjects, same
experiment. Stretch reflexes were evoked via a stretch device capable of evoking
stretch reflexes of the human soleus muscles during walking. H-reflexes were
elicited by an electrical stimulation of the tibial nerve at the popliteal fossa
at the knee. A significantly different modulation of the two reflexes was found
in the late stance where the stretch reflex decreased in relation to the H
reflex. This was consistent with the unloading of the muscle spindles during the
push-off in the late stance, suggesting a complex alpha-gamma coactivation, if
any, at this time of the step. The soleus stretch reflex and H-reflex were
compared during the stance phase of walking and sitting at matched soleus
activity. No difference was found in the amplitude of the stretch reflex.
However, there was a significant decrease of the H-reflex during the stance phase
of walking, consistent with a task-specific presynaptic mediated reflex control.
It is proposed that the short latency stretch reflex during walking is not
sensitive to such a presynaptic inhibition.
PMID- 10198148
TI - Analysis of the role of proprioceptive information during arm movements using a
model of the human arm.
AB - Using a model for the neuromuscular control of human arm movements, the possible
roles of different proprioceptive signals are analyzed. The control model is
represented by a neural network and includes both feedback and feedforward
control modes. After a learning process, the controller regulates a wide range of
arm movements. Evaluation of the roles of different afferent signals shows that
sensed muscle forces are important to achieve accurate control of fast movements.
For a moderately high look delay (50 ms), velocity feedback is not essential, but
for small look delays (0 to 25 ms) an increased performance is attained by
feedback of velocity. Position sense is essential to prevent steady-state errors.
The arm impedance is affected considerably by the delay in the control loop and
by the configuration of the motor control system. The achieved relation between
muscle length and force is similar to the invariant characteristics laying at the
basis of the equilibrium-point (EP) hypothesis. However, control of fast
movements on the basis of EP along is not feasible, but required feedforward
control. During training in a velocity-dependent force field, the impedance of
the arm increases at first, due to enhanced cocontraction. Subsequently, both
impedance and movement errors decrease, indicating a successful representation of
the changed inverse dynamics.
PMID- 10198149
TI - How locomotor parameters adapt to gravity and body structure changes during gait
development in children.
AB - The principles of direct dynamics and oscillating systems have been used to study
the development of gait parameters in children, with respect to their kinetic
consequences on the oscillations of body center of mass (CM). In particular the
equations established (a) a natural body frequency (NBF), a body parameter
specific to oscillating movements which is invariant for adults and decreases
with age for children, and (b) the amplitude ratio of CM to center-of-foot
pressure (CP) oscillations as a parametric function of the step frequency, whose
parameter is the NBF. This function was used to analyze the development of gait
locomotors with respect to their kinetic effects on balance in the frontal plane.
Five children were examined longitudinally during their first 5 years of
independent walking (IW), and two cross-sectional groups between 5 and 7 years of
IW were also considered. The results showed a shift toward the low end of step
frequency bands as the NBF decreased along with invariances in the amplitudes of
CM oscillation in both the frontal and sagittal planes, regardless of age and
gait velocity. The biomechanical meaning of the NBF, of its decrease and of
postural invariances associated with the decrease of the frequency, are discussed
as well as how the programming of locomotor parameters adapts to changes in body
structure during gait development.
PMID- 10198151
TI - Assistance in manuscript presentation
PMID- 10198150
TI - Cross-education of muscle strength is greater with stimulated than voluntary
contractions.
AB - Cross-education enhances the performance of muscles not directly involved in the
chronic conditioning of the muscles in a remote limb. Substantial cross-education
occurs after training with eccentric contractions or with contractions evoked by
electromyostimulation (EMS). Since during EMS and eccentric contractions, skin
and muscle afferents are activated that have excitatory effects on contralateral
homologous muscles, it was hypothesized that exercise training with stimulated
vs. voluntary eccentric contractions would lead to greater cross-education.
Thirty-two women were randomly assigned to a voluntary (Vol), an EMS, or remote
EMS (rEMS) exercise group and performed 840 voluntary or stimulated eccentric
contractions over 6 weeks. All subjects, including nonexercising controls (Con),
were tested pre- and posttraining for maximal voluntary and stimulated isometric
and eccentric quadriceps strength. Ipsilateral voluntary and stimulated forces
increased in all groups. Changes in EMG activity paralleled those in voluntary
force in each limb. No changes occurred in grip strength. The great contra- and
ipsilateral strength gains after EMS training were most likely related to an
additive effect of EMS and muscle lengthening.
PMID- 10198152
TI - Propionic acid stimulates superoxide generation in human neutrophils.
AB - Short-chain carboxylic acids are the metabolic by-products of pathogenic
anaerobic bacteria and are found at sites of infection in millimolar quantities.
We previously reported that propionic acid, one of the short-chain carboxylic
acids, induces an increase in intracellular Ca2+ ([Ca2+]i) in human neutrophils.
Here we investigate the effect of propionic acid on superoxide generation in
human neutrophils. Propionic acid (10 mm) induced inositol 1,4, 5-trisphosphate
(IP3) formation and a rapidly transient increase in [Ca2+]i, but not superoxide
generation, whereas 1 microm formylmethionyl-leucyl-phenylalanine (fMLP), a
widely used neutrophil-stimulating bacterial peptide, stimulated not only IP3
formation and Ca2+ mobilization but also superoxide generation. The IP3 level
induced by propionic acid was slightly lower than that induced by fMLP. The
transient increase in [Ca2+]i induced by propionic acid immediately returned to
the basal level, whereas a sustained increase in [Ca2+]i, which was higher than
the basal level, following a transient increase in [Ca2+]i was induced by fMLP.
The peak level induced by propionic acid was lower than that with fMLP. In the
absence of extracellular Ca2+, thapsigargin, a potent inhibitor of endoplasmic
reticulum Ca2+-ATPase, induced an increase in [Ca2+]i even after propionic acid
stimulation, but not after fMLP. The Ca2+ ionophore A23187 and thapsigargin
induced superoxide generation by themselves. Propionic acid enhanced the
superoxide generating effect of A23187 and thapsigargin. These results suggest
that Ca2+ mobilization induced by propionic acid is much weaker than that with
fMLP, and propionic acid is able to generate superoxide in the presence of a Ca2+
ionophore and a Ca2+ influx activator.
PMID- 10198153
TI - Tyrosine kinase inhibitors reverse butyrate stimulation of human Caco-2
intestinal epithelial cell alkaline phosphatase but not butyrate promotion of
dipeptidyl dipeptidase.
AB - Short chain fatty acids such as sodium butyrate are concentrated in the colonic
lumen and may protect against colon carcinogenesis by maintaining colonocytic
differentiation, but the mechanisms by which they act are not fully understood.
It has recently been suggested that short chain fatty acids modulate cellular
tyrosine kinase activity in addition to altering chromatin structure via
regulation of histone acetylation and DNA methylation. Therefore, the authors
evaluated the influence of tyrosine kinase inhibition on the effects of 10 mM
butyrate on human Caco-2 intestinal epithelial differentiation, using alkaline
phosphatase and dipeptidyl dipeptidase specific activity as markers of
differentiation, and two tyrosine kinase inhibitors, of different mechanisms of
action and different effects on Caco-2 brush border enzyme specific activity, to
block tyrosine kinase activity. As expected, butyrate stimulated both alkaline
phosphatase and dipeptidyl dipeptidase specific activity. The tyrosine kinase
inhibitors prevented, and indeed one inhibitor reversed the effects of butyrate
on alkaline phosphatase specific activity. However, tyrosine kinase inhibition
did not prevent butyrate stimulation of dipeptidyl dipeptidase specific activity.
Different pathways are likely to regulate the effects of butyrate on expression
of these two brush border enzymes. Butyrate stimulation of alkaline phosphatase,
but not dipeptidyl dipeptidase, may involve tyrosine phosphorylation signaling.
PMID- 10198154
TI - Creatine kinase and creatine kinase isoenzyme responses to heat stress.
AB - During this investigation the effects of heat acclimation and exercise on
creatine kinase and creatine kinase BB isoenzyme responses in various tissues and
serum of male Sprague-Dawley rats were ascertained. Forty rats were randomly
divided into two groups of 20 rats each. One group was housed at 22+/-1 degrees C
and the other at 33+/-1 degrees C. Each of the two groups were subdivided into
two subgroups of ten rats each. One subgroup of each group was subjected to a
programme of treadmill running of progressive intensity over a period of 6 weeks
at the temperature at which it was housed while the other served as a resting
control. At the end of the acclimation programme the rats were running at 23
m/min for 80 min. On the day of sacrifice all four subgroups were subjected to a
discontinuous exercise protocol (10 min running alternated by a 2-min rest
period; repeated three times) at 30+/-1 degrees C on a rodent treadmill at 23
m/min. The tissues investigated were kidney, heart and muscle. The rats were
anaesthetized with pentobarbital sodium (6 mg/100 g body mass) injected
intraperitoneally. The tissues were freeze-clamped and stored in liquid air until
analysed. The body temperature of the four subgroups at the end of the
experimental protocol were not significantly different. Acclimation at 33+/-1
degrees C resulted in significantly lower creatine kinase activity levels.
Exercise at 30+/-1 degrees C also resulted in decreased creatine kinase activity
levels in both acclimated groups. A similar trend was observed regarding creatine
kinase BB isoenzyme activity levels, especially in kidney.
PMID- 10198155
TI - Multinucleation and preservation of nucleolar integrity of macrophages.
AB - Rat bone marrow-derived macrophages formed multinucleated giant cells
spontaneously when cultured in slide glass chambers or when induced with the
polyanion acetyl lignin. Nuclei in such cells tended to cluster in distinct
rings. DNA fragmentation appeared to occur in multinucleated cells, as detected
by 3' end-labeling. Southern blot analyses, using probes specific for nucleolar
and non-nucleolar genes, indicated that chromatin DNA was fragmented whereas
nucleolar DNA was relatively intact. Autoradiography revealed preservation, in
multinucleated cells, of nucleoli into which radiolabeled uridine was
incorporated. Multinucleated macrophages appeared to eventually fragment.
Preserved integrity of nucleoli seems to be a feature of macrophage
multinucleation, a process which apparently culminates in cell death.
PMID- 10198157
TI - The belgian society for cell biology41st ordinary meeting: calcium signalling
PMID- 10198156
TI - G2 restriction point within populations of hepatocytes and tongue keratinocytes
in young, growing mice.
AB - The authors studied the effect of either extracts from liver (LE) or the
malignant tumour ES2 (TE) or plasma from intact mice (PI) or tumour-bearing
animals (PT) on the mitotic activity of the hepatocytes and tongue keratinocytes
in young, growing C3H/s male mice (28+/-1 days old). Animals standardized for
periodicity analysis were injected intraperitoneally with either TE, LE, PI, PT,
or saline (S) at 16:00 h with 0.01 ml of sample/g of body weight and were then
killed at (time of day/h post-injection) 20:00/04, 00:00/08, and 04:00/12.
Colchicine (2 microg/g) was injected 4 h before death. Samples of the liver and
tongue from each animal were processed for histology and assessment of mitotic
index. The results were expressed as colchicine-arrested metaphases/1000 nuclei.
The TE and LE stimulated the mitotic activity of hepatocytes and tongue
keratinocytes. Taking into account the time elapsed between the injections and
the measurements made in these light-dark synchronized animals, we conclude that
the increase in mitotic index observed in those tissues stemmed from a
reinitiation of cell-cycle traverse in a subpopulation of G2-arrested, noncycling
cells.
PMID- 10198158
TI - Molecular cloning and characterization of the human CLOCK gene: expression in the
suprachiasmatic nuclei.
AB - The Clock gene is an essential regulator of circadian rhythms. It encodes a
member of the basic helix-loop-helix/PER-ARNT-SIM family of transcription factors
known to play a central role in the control of diverse cellular events.
Previously we described the functional identification and molecular isolation of
the Clock gene in the mouse, its interaction with the BMAL1 protein, and the role
of this complex as a transcriptional activator in the circadian pacemaker. Here,
we report the cloning, exon organization, chromosomal location, and mRNA
expression of the human CLOCK gene. The coding sequence of human CLOCK extends
for 2538 bp and is 89% identical to its mouse ortholog; its deduced amino acid
sequence is 846 residues long and is 96% identical to mouse CLOCK. Radiation
hybrid mapping localized human CLOCK to the long arm of human chromosome 4
(4q12). Direct sequencing of a genomic CLOCK clone indicated that the coding
sequence of human CLOCK extends over 20 exons and that its intron/exon
organization is identical to that of the mouse ortholog. Northern blot analysis
indicated widespread expression of two major transcripts of 8 and 10 kb, and in
situ hybridization of human brain tissue revealed elevated expression of CLOCK
mRNA in the suprachiasmatic nuclei, the locus of circadian control in mammals,
and in the cerebellum. Comparison of cDNA clones revealed two single nucleotide
polymorphisms in noncoding sequence flanking the CLOCK open reading frame. The
central role of Clock in the organization of circadian rhythms suggests that it
will be a useful candidate gene for genetic analyses of disorders associated with
dysfunction of the circadian system.
PMID- 10198159
TI - The Bax inhibitor-1 gene is differentially regulated in adult testis and
developing lung by two alternative TATA-less promoters.
AB - We identified Bax inhibitor-1, BI-1, as a developmentally regulated gene product
in perinatal lung using suppressive subtractive hybridization. BI-1 is a novel
suppressor of apoptosis that was previously cloned as testis-enhanced gene
transcript (TEGT). However, sequence analysis of lung BI-1 revealed unique
nucleotides starting 29 bases upstream of the ATG initiation codon and extending
to the 5' end of lung-derived BI-1 cDNA compared to the original transcript from
the testis. Cloning and sequencing of the upstream region of the BI-1 gene
revealed that these unique sequences originated from two alternative first exons,
located in tandem and separated by approximately 600 bases. Neither was preceded
by a TATA box in the usual position, and S1 nuclease mapping at each exon 1
revealed multiple transcription start points with a major site being overlapped
by a consensus initiator element. Promoter activity from each region was
documented by transient transfection analysis in vitro using DNA sequences
ligated to a reporter gene. The proximal promoter, P1, may exhibit cell type
specific differences in fibroblasts versus epithelia, whereas the distal
promoter, P2, may exhibit species-specific differences in rat versus human cells.
RT-PCR analysis for expression in adult tissues using exon 1-specific 5' primers
and common 3' primers revealed that P1 is tissue-specific; P2 is ubiquitously
active. The developmental regulation of BI-1 in the late fetal and early
postnatal lung is specific for P2, indicating that these two TATA-less promoters
are differentially regulated in adult testis and developing lung. Since Bax
inhibitor-1 functions as a suppressor of apoptosis, its expression could provide
a survival advantage for select cell populations during the peak period of
apoptosis that occurs at birth.
PMID- 10198160
TI - Transcription map of Xq27: candidates for several X-linked diseases.
AB - Human Xq27 contains candidate regions for several disorders, yet is predicted to
be a gene-poor cytogenetic band. We have developed a transcription map for the
entire cytogenetic band to facilitate the identification of the relatively small
number of expected candidate genes. Two approaches were taken to identify genes:
(1) a group of 64 unique STSs that were generated during the physical mapping of
the region were used in RT-PCR with RNA from human adult and fetal brain and (2)
ESTs that have been broadly mapped to this region of the chromosome were finely
mapped using a high-resolution yeast artificial chromosome contig. This combined
approach identified four distinct regions of transcriptional activity within the
Xq27 band. Among them is a region at the centromeric boundary that contains
candidate regions for several rare developmental disorders (X-linked recessive
hypoparathyroidism, thoracoabdominal syndrome, albinism-deafness syndrome, and
Borjeson-Forssman-Lehman syndrome). Two transcriptionally active regions were
identified in the center of Xq27 and include candidate regions for X-linked
mental retardation syndrome 6, X-linked progressive cone dystrophy, X-linked
retinitis pigmentosa 24, and a prostate cancer susceptibility locus. The fourth
region of transcriptional activity encompasses the FMR1 (FRAXA) and FMR2 (FRAXE)
genes. The analysis thus suggests clustered transcription in Xq27 and provides
candidates for several heritable disorders for which the causative genes have not
yet been found.
PMID- 10198161
TI - Refined genetic and physical localization of the Wagner disease (WGN1) locus and
the genes CRTL1 and CSPG2 to a 2- to 2.5-cM region of chromosome 5q14.3.
AB - Wagner syndrome (WGN1; MIM 143200), an autosomal dominant vitreoretinopathy
characterized by chorioretinal atrophy, cataract, and retinal detachment, is
linked to 5q14.3. Other vitreoretinopathies without systemic stigmata, including
erosive vitreoretinopathy, are also linked to this region and are likely to be
allelic. Within the critical region lie genes encoding two extracellular
macromolecules, link protein (CRTL1) and versican (CSPG2), which are important in
binding hyaluronan, a significant component of the mammalian vitreous gel, and
which therefore represent excellent candidates for Wagner syndrome. Genetic
mapping presented here in two further families reduces the critical region to
approximately 2 cM. Subsequent refinement of the physical map allows ordering of
known polymorphic microsatellites and excludes CRTL1 as a likely candidate for
the disorder. CSPG2 is shown to lie within the critical region; however, analysis
of the complete coding region of the mature peptide reveals no clear evidence
that it is the gene underlying WGN1.
PMID- 10198162
TI - cDNA cloning and mapping of a novel subtype of glutamine:fructose-6-phosphate
amidotransferase (GFAT2) in human and mouse.
AB - We subcloned human and mouse full-length cDNAs of a novel subtype of
glutamine:fructose-6-phosphate amidotransferase (GFAT), which was designated
GFAT2 (the previously reported GFAT was named GFAT1). Both the human and the
mouse GFAT2 proteins deduced from their open reading frame sequences are composed
of 682 amino acids of approximately 77.0 kDa. At the amino acid level, homologies
between the human GFAT1 and GFAT2, between the mouse GFAT1 and GFAT2, and between
the human GFAT2 and the mouse GFAT2 were 75.6, 74.7, and 97. 2%, respectively.
Northern blot analysis using probe specific to human GFAT1 or GFAT2 showed that
major transcripts were approximately 3.0 kb in both the human GFAT subtypes. The
analysis also revealed different tissue distribution between GFAT1 and GFAT2:
GFAT1 was more highly expressed in the placenta, pancreas, and testis than GFAT2;
GFAT2 was expressed throughout the central nervous system, especially in the
spinal cord, but GFAT1 expression was weak. The locus was mapped to human
chromosome 5q and mouse chromosome 11, where a synteny between the two species
has been known. GFAT2 can provide insights into understanding the roles of the
hexosamine pathway in various tissues, particularly with the development of
glucose toxicity and diabetes complications.
PMID- 10198163
TI - Characterization and expression pattern of the frizzled gene Fzd9, the mouse
homolog of FZD9 which is deleted in Williams-Beuren syndrome.
AB - The frizzled gene family is conserved from insects to mammals and codes for
putative Wnt receptors that share a cysteine-rich extracellular domain and seven
transmembrane domains. We previously identified a novel frizzled gene, FZD3, now
renamed FZD9, in the Williams-Beuren syndrome (WBS) deletion region at
chromosomal band 7q11.23 and showed that its product can interact with the
Drosophila wingless protein. Here, we report the characterization of the mouse
homolog Fzd9. The Fzd9 gene produces a 2.4-kb transcript encoding a 592-amino
acid protein with 95% identity to the human FZD9. Fzd9 was mapped to the
conserved syntenic region on distal mouse chromosome 5. By RNA in situ
hybridization studies of whole-mount embryos and sections we delineated the
temporal and spatial expression patterns in the neural tube, trunk skeletal
muscle precursors (myotomes), limb skeletal anlagen, craniofacial regions, and
nephric ducts. In adult mouse tissue, the Fzd9 transcript is abundantly present
in heart, brain, testis, and skeletal muscle. In testis, Fzd9 is expressed in all
spermatogenic cell types. Immunohistochemical studies of cells transfected with a
Fzd9 expression construct confirm that Fzd9 is a membrane protein. These results
suggest potential Wnt ligands of Fzd9, a role of Fzd9 in skeletal muscle
specification, and contributions of FZD9 to the WBS phenotype.
PMID- 10198164
TI - A 1-Mb BAC/PAC-based physical map of the autosomal recessive polycystic kidney
disease gene (PKHD1) region on chromosome 6.
AB - The PKHD1 (polycystic kidney and hepatic disease 1) gene responsible for
autosomal recessive polycystic kidney disease has been mapped to 6p21.1-p12 to an
approximately 1-cM interval flanked by the markers D6S1714/D6S243 and D6S1024. We
have developed a sequence-ready BAC/PAC-based contig map of this region as the
next step for the positional cloning of PKHD1. This contig comprising 52 clones
spanning approximately 1 Mb was established by content mapping of 44 BAC/PAC-end
derived STSs, 3 known genetic markers, 5 YAC-end-derived STSs, 3 random STSs, 1
previously mapped gene, and 1 EST. The average depth per marker is 6.3 clones,
and the average STS density is 20 kb. The genomic clone overlaps were confirmed
by restriction fragment fingerprint analysis. A high-resolution BAC/PAC-based
contig map is essential to the ultimate goal of identifying the PKHD1 gene.
PMID- 10198165
TI - A single human myosin light chain kinase gene (MLCK; MYLK).
AB - The myosin light chain kinase (MLCK) gene, a muscle member of the immunoglobulin
gene superfamily, yields both smooth muscle and nonmuscle cell isoforms. Both
isoforms are known to regulate contractile activity via calcium/calmodulin
dependent myosin light chain phosphorylation. We previously cloned from a human
endothelial cell (EC) cDNA library a high-molecular-weight nonmuscle MLCK isoform
(EC MLCK (MLCK 1) with an open reading frame that encodes a protein of 1914 amino
acids. We now describe four novel nonmuscle MLCK isoforms (MLCK 2, 3a, 3b, and 4)
that are the alternatively spliced variants of an mRNA precursor that is
transcribed from a single human MLCK gene. The primary structure of the cDNA
encoding the nonmuscle MLCK isoform 2 is identical to the previously published
human nonmuscle MLCK (MLCK 1) (J. G. N. Garcia et al., 1997, Am. J. Respir. Cell
Mol. Biol. 16, 489-494) except for a deletion of nucleotides 1428-1634 (D2). The
full nucleotide sequence of MLCK isoforms 3a and 3b and partial sequence for MLCK
isoform 4 revealed identity to MLCK 1 except for deletions at nucleotides 5081
5233 (MLCK 3a, D3), double deletions of nucleotides 1428-1634 and 5081-5233 (MLCK
3b), and nucleotide deletions 4534-4737 (MLCK 4, D4). Northern blot analysis
demonstrated the extended expression pattern of the nonmuscle MLCK isoform(s) in
both human adult and human fetal tissues. RT-PCR using primer pairs that were
designed to detect specifically nonmuscle MLCK isoforms 2, 3, and 4 deletions
(D2, D3, and D4) confirmed expression in both human adult and human fetal tissues
(lung, liver, brain, and kidney) and in human endothelial cells (umbilical vein
and dermal). Furthermore, relative quantitative expression studies demonstrated
that the nonmuscle MLCK isoform 2 is the dominant splice variant expressed in
human tissues and cells. Further analysis of the human MLCK gene revealed that
the MLCK 2 isoform represents the deletion of an independent exon flanked by 5'
and 3' neighboring introns of 0.6 and 7.0 kb, respectively. Together these
studies demonstrate for the first time that the human MLCK gene yields multiple
nonmuscle MLCK isoforms by alternative splicing of its transcribed mRNA precursor
with differential distribution of these isoforms in various human tissues and
cells.
PMID- 10198166
TI - Isolation and functional characterization of the human 90K promoter.
AB - 90K is a secreted protein thought to be involved in the body's defense against
pathogens and cancer. To elucidate its transcriptional regulation, the promoter
of human 90K (HGMW-approved symbol LGAL S3BP) was isolated and characterized.
Analysis of the 3. 3-kb 5'-flanking region revealed that it is a TATA-less
promoter, but neither GC-rich nor dependent on SP1 sites. RNase protection assays
detected one major transcription start site (+1) and several minor transcription
start sites upstream and downstream. Deletion studies defined a minimal promoter
(-103 --> -49) and indirectly suggested positive synergism between different
elements within it. Consistent with the proposed function of 90K, its promoter
activity could be stimulated by poly(I). poly(C), mimicking viral infection. Two
regions mediating induction by poly(I). poly(C) (-171 --> -112, -32 --> 46) were
identified by deletion mutants. A small region around the minimal promoter (-99 -
> -12) was highly homologous between human and mouse. While both human and mouse
minimal promoters contained an interferon-responsive element (IRF-E), the human
minimal promoter was not inducible by poly(I). poly(C) in contrast to that of the
mouse. Point mutations 30 bp upstream of the IRF-E, however, conferred
inducibility to the human minimal promoter, suggesting interaction between
different promoter elements.
PMID- 10198167
TI - Identification of a putative transcription factor gene (WBSCR11) that is commonly
deleted in Williams-Beuren syndrome.
AB - Williams-Beuren syndrome (WBS) is a complex developmental disorder involving the
hemizygous deletion of genes on chromosome 7q11.23. The cardiovascular aspects of
the disorder are known to be caused by haploinsufficiency for ELN, but the genes
contributing to the other features of WBS are still undetermined. Fifteen genes
have been shown to reside within the WBS deletion, and here we report the
identification and cloning of an additional gene that is commonly deleted.
WBSCR11, which was identified through genomic DNA sequence analysis and cDNA
library screening, was positioned toward the telomeric end of the WBS deletion.
The gene is expressed in all adult tissues analyzed, including many regions of
the brain. The predicted protein displays homology to another gene from the WBS
deletion, GTF2I, which is known to be a transcription factor. We postulate that
WBSCR11 is also a transcription factor and may contribute to the spectrum of
developmental symptoms found in WBS.
PMID- 10198168
TI - cDNA characterization and chromosomal mapping of human golgi SNARE GS27 and GS28
to chromosome 17.
AB - Transport of proteins along the exocytotic pathway is primarily achieved by
vesicular intermediates. Two proteins, Golgi SNAREs of 27 kDa, GS27, and of 28
kDa, GS28 (HGMW-approved nomenclature GOSR2 and GOSR1, respectively), are
important trafficking membrane proteins between the endoplasmic reticulum and the
Golgi and between Golgi subcompartments. Here, we present the human GS27 and GS28
cDNA sequences. They encode predicted proteins of 212 and 250 amino acids,
respectively. Chromosomal mapping analyses reveal that human GS27 is located on
chromosome 17q21 and GS28 on approximately 17q11. The chromosomal location of
GS27 near a locus implicated in familial essential hypertension and its known
function in trafficking indicate that it is a potential candidate gene for this
disease.
PMID- 10198169
TI - Linkage of the nuclear hormone receptor genes NR1D2, THRB, and RARB: evidence for
an ancient, large-scale duplication.
AB - The THRA gene encoding thyroid hormone receptor alpha shares an unusual partial
overlap with the NR1D1 gene encoding the orphan receptor Rev-ErbAalpha. Though
THRA and NR1D1 have close relatives in THRB and NR1D2, which encode TRbeta and
Rev-ErbAbeta, these beta isoforms do not share an analogous overlap. Here we
report that the human THRB and NR1D2 genes are separated by approximately 1 Mb on
chromosome 3 and that these two genes are also linked to the RARB gene, which
encodes retinoic acid receptor beta. Since previous results indicate that the
THRA/NR1D1 locus is also linked to the RARA gene, these results suggest that the
two receptor gene clusters were generated by a single large-scale duplication.
PMID- 10198170
TI - Invertebrate tissue inhibitor of metalloproteinase: structure and nested gene
organization within the synapsin locus is conserved from Drosophila to human.
AB - Vertebrate tissue inhibitors of metalloproteinases (TIMPs) regulate extracellular
matrix metalloproteinases and are thus involved in a wide variety of
developmental and physiological processes. By identifying cDNAs of a transcript
detected within an intron of the Drosophila synapsin gene we have cloned the
Drosophila TIMP gene (Timp), which represents the first invertebrate member of
the TIMP gene family. Sequence analysis revealed an open reading frame of 210
amino acids with 35% identity to human TIMPs and a conserved exon-intron
structure. Analysis of sequence data from the Sanger Centre demonstrated that the
human TIMP3 gene is encoded within intron V of the human synapsin-III gene,
indicating that the nested organization of TIMP and synapsin genes may be a
general feature conserved in evolution. We therefore speculate that the human
TIMP4 gene will be located in intron V of the human synapsin-II gene on
chromosome 3p25, and we present preliminary evidence that a human synapsin-IV
gene is located near the TIMP2 gene on chromosome 17q23-q25.
PMID- 10198171
TI - Cloning and chromosomal localization of human Cdc42-binding protein kinase beta.
AB - The p21 GTPases, Rho and Cdc42, regulate numerous cellular functions by binding
to members of a serine/threonine protein kinase subfamily. These functions
include the remodeling of the cell cytoskeleton that is a feature of cell growth
and differentiation. Two of these p21 GTPase-regulated kinases, the myotonic
dystrophy protein kinase-related Cdc42-binding kinases (MRCKalpha and beta), have
been recently characterized in rat. Both of these proteins phosphorylate
nonmuscle myosin light chain, a prerequisite for the activation of actin-myosin
contractility. Here we report the cDNA cloning of the human homologue of
MRCKbeta, CDC42BPB, which was found by Northern blot analysis to be expressed in
a wide range of tissues. The human CDC42BPB gene maps to cytogenetic band 14q32.3
by FISH analysis.
PMID- 10198172
TI - The Sox-13 gene: structure, promoter characterization, and chromosomal
localization.
AB - We have recently identified the HMG box transcription factor Sox-13 and described
its expression during murine embryogenesis. Here we describe the structure of the
murine Sox-13 gene. This gene spans approximately 12 kb and consists of 13 exons.
The HMG domain is encoded by exons XI and XII, separated by an intron that is
conserved among Sox-5, Sox-13, and Sox-17. A single major transcription
initiation site was identified. Deletion analysis of the 3-kb promoter region
revealed a 400-bp fragment driving transcription of a luciferase reporter in a
Sox-13-expressing cell line. To determine the chromosomal localization of the
human gene, a human SOX13 cDNA was isolated with 75% homology to the mouse Sox
13. FISH analysis mapped the human SOX13 gene to chromosome 1 band q32.
PMID- 10198173
TI - A 1.5-Mb contig within the cat eye syndrome critical region at human chromosome
22q11.2.
AB - We have constructed a 1.5-Mb contig spanning the distal half of the critical
region for cat eye syndrome on human chromosome 22 from D22S543 to D22S181. The
contig consists of 20 P1 artificial chromosome (PAC) clones and 11 bacterial
artificial chromosome (BAC) clones screened from 2 BAC and 2 PAC libraries.
Continuous overlap between the clones was confirmed using vectorette PCR and
riboprobes. Despite the instability of this region in a previous YAC contig, only
1 BAC showed a minor instability and then in only one isolation. This contig is
now providing the basis for genomic sequencing and gene identification in the cat
eye syndrome critical region.
PMID- 10198174
TI - Localization of serine kinases, SRPK1 (SFRSK1) and SRPK2 (SFRSK2), specific for
the SR family of splicing factors in mouse and human chromosomes.
AB - The serine- and arginine-rich (SR) splicing factors play an important role in
both constitutive and alternative pre-mRNA splicing, and the functions of these
splicing factors are regulated by phosphorylation. We have previously
characterized SRPK1 (SFRSK1) and SRPK2 (SFRSK2), which are highly specific
protein kinases for the SR family of splicing factors. Here we report the
chromosomal localization of the mouse and human genes for both kinases. SRPK1
probes detected two loci that were mapped to mouse Chromosomes 17 and X using The
Jackson Laboratory interspecific backcross DNA panel, and SRPK2 probes identified
a single locus on mouse Chromosome 5. Using a somatic cell hybrid mapping panel
and by fluorescence in situ hybridization, SRPK1 and SRPK2 were respectively
mapped to human chromosomes 6p21.2-p21.3 (a region of conserved synteny to mouse
Chromosome 17) and 7q22-q31.1 (a region of conserved synteny to mouse Chromosome
5). In addition, we also found multiple SRPK-related sequences on other human
chromosomes, one of which appears to correspond to a SRPK2 pseudogene on human
chromosome 8.
PMID- 10198175
TI - Cloning, mapping, and genomic organization of the LSLCL gene, encoding a new
lymphocytic secreted mucin-like protein with a C-type lectin domain: A new model
of exon shuffling.
PMID- 10198176
TI - Assignment of the human helix-loop-helix transcription factor gene
musculin/activated B-cell factor-1 (MSC) to chromosome 8q21 and its mouse
homologue (Msc) to the proximal region of chromosome 1.
PMID- 10198177
TI - Chromosomal mapping of the tankyrase gene in human and mouse.
PMID- 10198178
TI - Mapping of the human NBC3 (SLC4A7) gene to chromosome 3p22.
PMID- 10198179
TI - Evolution and diversity of mammalian sodium channel genes.
PMID- 10198180
TI - Reduced Ca(2+)-sensitivity of SERCA 2a in failing human myocardium due to reduced
serin-16 phospholamban phosphorylation.
AB - It is still a matter of debate, whether decreased protein expression of SERCA 2a
and phospholamban (PLB), or alterations in the phosphorylation state of PLB are
responsible for the reduced SERCA 2a function in failing human myocardium. Thus,
in membrane preparations from patients with terminal heart failure due to
idiopathic dilated cardiomyopathy (NYHA IV. heart transplants) and control hearts
(NF), SERCA 2a activity was measured with an NADH coupled assay with as well as
without stimulation with protein kinase A (PKA). The protein expression of SERCA
2a, PLB and calsequestrin as well as the phosphorylation status of PLB (Back
phosphorylation technique: Serine-16-PLB specific antibody) were analysed using
Western blotting technique and specific antibodies. In NF, the maximal activity
(Vmax) and the Ca(2+)-sensitivity of SERCA 2a activity were significantly higher
compared to NYHA IV. Protein expression of SERCA 2a, PLB and calsequestrin were
unchanged, whereas both, the phosphorylation status of PLB as well as serine-16
PLB-phosphorylation, were significantly reduced in NYHA IV. After stimulation
with PKA only the Ca(2+)-sensitivity, but not Vmax increased concentration
dependently. Therefore, in human myocardium, the Ca(2+)-sensitivity but not the
Vmax of SERCA 2a is regulated by cAMP-dependent phosphorylation of phospholamban
at position serine-16. Threonine-17-PLB-phosphorylation or direct phosphorylation
of SERCA 2a may be candidates for regulation of maximal SERCA 2a activity in
human myocardium.
PMID- 10198181
TI - Glucose utilization and glycogen turnover are accelerated in hypertrophied rat
hearts during severe low-flow ischemia.
AB - We undertook this study to determine if the metabolism of exogenous glucose and
glycogen in hypertrophied hearts differed from that in normal hearts during
severe ischemia. Thus, rates of glycolysis (3H2O production) and oxidation (14CO2
production) from exogenous glucose and glycogen were measured in isolated working
control (n = 13) and hypertrophied (n = 12) hearts from sham-operated and aortic
banded rats during 40 min of severe low-flow ischemia. Hearts, in which glycogen
was prelabelled with [5-3H]- or [14C]-glucose, were paced and perfused with Krebs
Henseleit solution containing 1.2 mM palmitate, 5.5 mM [5-3H]- or [14C]-glucose
(different from the isotope used to label glycogen), 0.5 mM lactate and 100
microU/ml insulin during ischemia. Rates of glycolysis from exogenous glucose
(3301 +/- 122 v 2467 +/- 167 nmol/min/g dry wt, mean +/- S.E.M., P < 0.05) and
glucose from glycogen (808 +/- 27 v 725 +/- 21 nmol/min/g dry wt, P < 0.05) were
accelerated in hypertrophied hearts compared to control hearts. However, rates of
oxidation of exogenous glucose and glucose from glycogen were not significantly
different between the two groups. As observed in normoxic non-ischemic hearts,
glucose from glycogen was preferentially oxidized compared to exogenous glucose.
Additionally, rates of glycogen synthesis (167 +/- 7 v 140 +/- 9 nmol/min/g dry
wt, P < 0.05) were increased in hypertrophied hearts compared to control hearts
during severe low-flow ischemia indicating that glycogen turnover (i.e.
simultaneous synthesis and degradation) was accelerated in the hypertrophied
heart. Thus, we demonstrate that glucose utilization and glycogen turnover are
accelerated in the hypertrophied heart during severe low-flow ischemia as
compared to the normal heart.
PMID- 10198182
TI - Normothermic transfer times up to 3 min will not precondition the isolated rat
heart.
AB - Isolated, perfused heart preparations suffer an inevitable peri-operative delay
(POD) before retrograde perfusion restores coronary flow. By varying this
ischaemic period we investigated the threshold of POD-induced inadvertent
preconditioning (PC) in the rat heart. Hearts subjected to POD at 37 degrees C
increasing from 1, 2, 3, 5, 10 up to 15 min prior to 20 min retrograde perfusion
were further subjected to 30 min global, normothermic ischaemia and 30 min
reperfusion (index I/R). The functional recovery was 32 +/- 4.1% in hearts
subject to 1 min POD. After 3 min POD functional recovery started to improve and
peaked at 10 min POD (78 +/- 7.1%, P < 0.001). At 4 degrees C functional recovery
started to improve after 5 min POD and peaked at 10 min POD. To demonstrate that
the POD-mediated protection was true PC, two conventional models of PC were
established. In both models, hearts were retrogradely perfused within 1 min POD
prior to a standard PC protocol (one episode of 10 min ischaemia, or four
episodes of 5 min ischaemia). In the conventional PC models protection against
the index I/R was abolished using 100 microM 5-hydroxydecanoate (5-HD), the
mitrochondrial KATP channel inhibitor. Likewise, 10 min POD-mediated recovery at
37 degrees C (70 +/- 3.2%) was reversed by 100 microM 5-HD perfusion (36 +/-
5.9%; NS v.s. 2 min POD). We conclude: (1) the threshold for PC is greater than 3
min at 37 degrees C and greater than 5 min at 4 degrees C: (2) blockade of the
mitochondrial KATP channel abolishes protection in three models of PC in the rat
heart, including prolonged POD.
PMID- 10198183
TI - Smooth muscle cell transplantation into myocardial scar tissue improves heart
function.
AB - This study was designed to evaluate the effect of smooth muscle cell
transplantation into myocardial ventricular scar formed by cryo-necrosis. The
left ventricular free wall (LVFW) of adult rats was cryo-necrosed. At 4 weeks
after cryo-injury cultured fetal rat stomach smooth muscle cells (transplanted
group, n = 10) or culture medium (control, n = 10) were transplanted. Sham
animals (n = 8) were similarly operated but without cryo-necrosis and
transplantation. The animals were administered a daily maintenance dose of
cyclosporin A (5 mg/kg). At 8 weeks after cryo-injury, heart function was
evaluated using a Langendorff preparation. Myocardial scar and transplanted cells
were assessed histologically. Transplanted smooth muscle cells survived and
formed smooth muscle cell tissue, as assessed by immunostaining against smooth
muscle cell actin, within the myocardial scar. In the control hearts no muscle
tissue was found in the scar. Angiogenesis occurred (P < 0.001) in the
transplanted scar compared to the control scar. The transplanted cells increased
the scar thickness (P < 0.01) by hyperplasia and prevented (P < 0.001) the
dilatation of the ventricular chamber size compared to the controlled hearts. For
physiological left ventricular volumes of 0.04 to 0.28 ml, the systolic and
developed pressures in the transplanted group were greater (P < 0.001) than the
control group, but less (P < 0.001) than those of the sham group. Transplanted
smooth muscle cells formed smooth muscle tissue in myocardial scar tissue and
improved contractile function compared to control hearts.
PMID- 10198184
TI - Mutation of amino acids 246-251 alters nuclear accumulation of human heat shock
protein (HSP) 72 with stress, but does not reduce viability.
AB - The stress response includes up-regulation of heat shock protein (HSP) 72
expression and accumulation of the protein in the nucleus. This nuclear
accumulation of HSP72 is seen in many different settings, including the ischemic
heart. The identity of the signal(s) regulating nuclear concentration of HSP72
are unknown. We theorized that nuclear accumulation of HSP72 with stress
contributes to its protective properties in the ischemic heart and other tissues.
Before we can test this hypothesis we need to alter accumulation of HSP72. Using
site-directed mutagenesis we investigated the importance of amino acids 246-262
(KRKHKKDISQNKRAVRR), the presumed nuclear localization sequence (NLS), in nuclear
accumulation in response to stress. Three mutant constructs of this sequence,
985A(AAAHAADISQNKRAVRR), 97M (KRKHKKDISQNAAAVAR), and B1 (AAAHAADISQNAAAVAR),
were transfected into Cos cells. Analysis by exhaustive photon reassignment,
which allowed examination of the nucleus in sections, showed that both 985A and
B1 had decreased nuclear concentration with stress. A fusion protein with KRKHKK
and EGFP localized to the nucleus in the absence of stress, with prominent
accumulation in the nucleoli. Only B1, which also altered ATP binding, affected
viability after heat shock. We conclude that amino acids 246-251 influence
nucleolar accumulation of HSP72, but that this is not essential for early
survival after injury.
PMID- 10198185
TI - Inhibition of Na(+)-K+ pump alleviates the shortening of action potential
duration caused by metabolic inhibition via blockade of KATP channels in coronary
perfused ventricular muscles of guinea-pigs.
AB - The Na(+)-K+ pump is a consumer of intracellular ATP. We therefore examined
whether blockade of the Na(+)-K+ pump by cardiac glycosides could inhibit ATP
sensitive K+ (KATP) channels and prolong the action potential duration (APD) of
the guinea-pig ventricular muscles perfused with Tyrode's solution via the
coronary artery and stimulated at 3 Hz. The metabolic inhibition (MI) achieved by
application of 0.1 microM carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone
(a mitochondrial uncoupler) shortened the APD in a time-dependent manner. When
dihydroouabain (DHO, 5 microM) was introduced 5 min but not 10 min after
introduction of MI, the APD shortening was significantly attenuated. Application
of glibenclamide (1 microM), a blocker of KATP channels, introduced both 5 and 10
min after MI also alleviated the APD shortening: DHO did not alleviate the APD
shortening effect produced by cromakalim (5 microM), a KATP-channel opener. In
separate experiments using whole-cell patch-clamp techniques, we found that this
concentration of DHO (5 microM) depressed the Na(+)-K+ pump current of the guinea
pig ventricular myocytes from 210 to 100 pA (at 0 mV) or by 49.5%. We conclude
that, during early phase (approximately 5 min) of MI, the APD shortening mostly
results from the activation of KATP channels, and that even a approximately 50%
inhibition of the Na(+)-K+ pump by DHO leads to the blockade of KATP channels and
eventual lengthening of the APD.
PMID- 10198186
TI - Mitochondrial oxidative phosphorylation in heart from stressed cardiomyopathic
hamsters.
AB - Stress alone is generally not sufficient to produce serious disease, but stress
imposed upon pre-existing disease can contribute to disease progression. To
explore this phenomenon, cold-immobilization stress was imposed on young 12.5
month, necrotic phase with small vessel coronary spasm) and older (5 month,
quiescent phase, between necrosis and heart failure) cardiomyopathic hamsters.
Our hypothesis was that changes in mitochondrial energy processes are involved in
stress induced pathology. Polarographic and high performance liquid
chromatography (HPLC) techniques were used to measure mitochondrial respiration
and oxidative phosphorylation and concentrations of phosphocreatine and
adenylates, respectively, in hearts from young and old cardiomyopathic hamsters
(stressed and unstressed). No significant differences were found between the
young (2.5 month) and old (5 month) age groups in unstressed and stressed healthy
hamsters and between young (2.5 month) and old (5 month) unstressed
cardiomyopathic hamsters with respect to different parameters of mitochondrial
oxidative phosphorylation and with respect to concentration of bioenergetic
metabolites, except that ADP concentration was higher in older cardiomyopathic
hamsters. Application of stress uncovered differences between young and old
cardiomyopathic hamsters: respiration control index was lower and State 4
respiration was higher in young compared to old cardiomyopathic hamsters; whereas
the total concentration of ATP was decreased to the same level in both
cardiomyopathic groups when compared to control. Mitochondrial oxidative
phosphorylation in young cardiomyopathic hamsters was more sensitive to Ca2+, as
evidenced by partial uncoupling of respiration and oxidative phosphorylation,
than in older cardiomyopathic hamsters and controls. In conclusion, young
cardiomyopathic hamsters, i.e. in the necrotic phase of disease, were more
susceptible to stress induced changes in mitochondrial oxidative phosphorylation
than older cardiomyopathic hamsters and controls.
PMID- 10198187
TI - Phosphorylation state of hsp27 and p38 MAPK during preconditioning and protein
phosphatase inhibitor protection of rabbit cardiomyocytes.
AB - Small heat shock proteins (hsp) have been implicated in mediation of classic
preconditioning in the rabbit, Hsp27 is a terminal substrate of the p38 MAPK
cascade. One and 2D gel electrophoresis and immunoblotting of cell fractions was
used to determine p38 MAPK and hsp27 phosphorylation levels, respectively, during
in vitro ischemia in control, calyculin A (Cal A)-treated (protein phosphatase
inhibitor), SB203580-treated (p38MAPK inhibitor) and preconditioned (IPC)
isolated adult rabbit cardiomyocytes. The dual phosphorylation of p38 MAPK was
increased by early ischemia (30-60 min), after which there was a loss of total
cytosolic p38 MAPK. The ischemic increase of p38 MAPK dual phosphorylation was
enhanced by IPC. Cal A strongly activated dual phosphorylation of p38 MAPK in
oxygenated cells and this was maintained into early ischemia, SB203580 inhibited
the dual phosphorylation of p38 MAPK and attenuated the loss of total cytosolic
p38 MAPK. In each protocol, ischemia translocated hsp27 from the cytosolic
fraction to the cytoskeletal fraction at similar rates and extents, Hsp27
phosphorylation was quantitated as the fraction of diphosphorylated hsp27, based
on IEF mobility shifts of hsp27 phosphorylation isoforms. In oxygenated control
cells, cytosolic and cytoskeletal hsp27 was highly phosphorylated. After 90 min
ischemia, cytoskeletal hsp27 was markedly dephosphorylated. Cal A slightly
increased control cytoskeletal hsp27 phosphorylation. During ischemic incubation,
Cal A blocked ischemic dephosphorylation, SB203580 accelerated ischemic hsp27
dephosphorylation and injury, IPC insignificantly decreased the initial rate of
ischemic dephosphorylation of hsp27, but not the extent of dephosphorylation in
later ischemia. Phosphorylation is regulated by both kinase and phosphatase
activities. IPC protection was not correlated with a significant increase in
cytosolic or cytoskeletal hsp27 phosphorylation levels during prolonged (> 60-90
min) ischemia.
PMID- 10198189
TI - Apoptosis in a canine model of acute Chagasic myocarditis.
AB - Histologic, ultrastructural and nick end labeling studies were made to evaluate
the occurrence of apoptosis in the hearts of dogs with acute myocarditis due to
experimental infection with T. cruzi. The best results for the detection of
apoptosis by nick end labeling were obtained by a method combining the use of
terminal deoxynucleotidyl transferase, CoCl2 and fluorescein-conjugated
deoxyuridine triphosphate, followed by counterstaining of DNA with 4'6-diamidino
2-phenylindole (DAPI) and examination by laser scanning confocal fluorescence
microscopy. Apoptosis was found in: (1) cardiac myocytes; (2) endothelial cells
of capillaries and venules: (3) immune effector cells, including macrophages,
interstitial dendritic cells (antigen-presenting cells) and granular and
agranular lymphocytes, and (4) intra- and extracellular forms of T. cruzi. The
apoptosis in myocytes and endothelial cells affected cells that were not infected
by T. cruzi and was probably caused by the release of toxic mediators of
inflammation. The apoptosis of immune effector cells could be related either to
the subsidence of inflammation or to modulation (and even failure) of the immune
response. The finding of apoptosis in T. cruzi confirms the results of other
studies showing that this phenomenon occurs during the differentiation of
trypomastigotes in vitro. Thus, apoptosis constitutes an important and
multifactorial event in the pathogenesis of acute Chagasic myocarditis.
PMID- 10198188
TI - Binding of the stress protein alpha B-crystallin to cardiac myofibrils correlates
with the degree of myocardial damage during ischemia/reperfusion in vivo.
AB - Stress proteins are assumed to protect cells against various kinds of stresses
including ischemia. In this study, we focused on the behaviour of the most
abundant myocardial stress protein, alpha B-crystallin, during ischemia and
reperfusion of the pig heart in vivo, alpha B-crystallin constitutes 1-2% of the
soluble protein pool and underwent, during severe but reversibly damaging
ischemia (25 min), complete translocation to the Z-line area of myofibrils.
Irreversibly damaging ischemia (60 min) was accompanied by extreme stretching of
the majority of myofibrils, and by concomitant extension of alpha B-crystallin
localization from the Z-line area to I-bands. This I-band shift correlated with
displacement of the T12 epitope of titin from the vicinity of Z-lines into I
bands, indicating that the primary binding sites for alpha B-crystallin might
also be located in juxtaposition to Z-lines and move into the I-bands during
extreme sarcomeric stretching. During reperfusion after 25 min of ischemia, alpha
B-crystallin disappeared rapidly from myofibrils: whereas reperfusion after
irreversibly damaging ischemia (60 min) resulted in dissociation of alpha B
crystallin only from those myofibrils and myocardiocytes that were still able to
contract, and alpha B-crystallin remained bound to the overstretched, damaged
myofibrils no longer capable of contraction. The time course of translocation of
alpha B-crystallin to myofibrils during ischemia correlated with phosphorylation
of approximately 20% of the entire alpha B-crystallin pool. However,
disappearance of alpha B-crystallin from myofibrils during reperfusion was not
accompanied by dephosphorylation, indicating that phosphorylation alone does not
explain myofibrillar binding of alpha B-crystallin. Ischemia-induced myofibrillar
targeting of alpha B-crystallin probably requires additional structural and
posttranslational modifications of myofibrillar components in juxtaposition to I
bands.
PMID- 10198190
TI - Cross-talk between cardiac kappa-opioid and beta-adrenergic receptors in
developing hypertensive rats.
AB - The kappa-opioid receptor exerts a negative modulatory action on the beta
adrenoceptor and the action is blunted in adult spontaneously hypertensive rats
(SHR). In order to determine whether the blunted negative modulation of the beta
adrenoceptor by the kappa-opioid receptor contributes to the development of
hypertension, the electrically induced intracellular calcium ([Ca2+]i) transient
was measured in single ventricular myocytes of SHR at 4, 6, 8 and 13-week-old and
the age-matched Wistar Kyoto (WKY) rats. The electrically induced [Ca2+]i
transients were augmented by norepinephrine (NE), a beta-adrenoceptor agonist,
over four-fold in WKY rats of all ages studied and in SHR of 4 and 6 weeks of
age. The enhancing effect of NE in 8- and 13-week-old SHR was, however, only
approximately three-fold, significantly lower than the corresponding values in
age-matched WKY rats. Similarly, the electrically induced [Ca2+]i transients were
also augmented by forskolin, an activator of adenylate cyclase, by approximately
two-fold in WKY rats of all ages and SHR aged 4 and 6 weeks. In SHR aged 8 and 13
weeks, the effect of forskolin was only 1.5-fold, significantly lower than the
two-fold increase in the corresponding WKY rats. The enhancing effects of NE and
forskolin were attenuated by U50,488H, a selective kappa-opioid agonist, by
approximately 50 and 25%, respectively, in both types of rats of all ages
studied, with the exception of 13-week-old rats. In rats of this age group, the
attenuations by U50,488H on the enhancing effects of NE and forskolin were 17 and
9% in SHR, respectively, significantly less than the corresponding 54 and 29% in
WKY. The fact that attenuation of U50,488H on the enhancing effects of NE and
forskolin only occurs in 13-week-old SHR when hypertension has been fully
developed indicates that the attenuated inhibitory modulation of kappa-opioid
receptor stimulation does not contribute to the initiation of hypertension.
Interestingly, the enhancing effects of NE and forskolin on the electrically
induced [Ca2+]i transient was attenuated in SHR aged from 8 weeks when the blood
pressure was rapidly increasing. The different time courses of altered responses
to U50,488H, and NE and forskolin suggest that the attenuated negative modulation
of kappa-receptor stimulation on the beta-adrenergic receptor is not due to the
signal transduction pathway activated by beta-adrenergic stimulation. In 13-week
old SHR with the arterial blood pressure restored to normal by pharmacological
manipulations, the blunted responses to NE, U50,488H and forskolin still
occurred, indicating that the altered responses to activation of beta-adrenergic
and kappa-opioid receptors and adenylate cyclase are not secondary to
hypertension.
PMID- 10198191
TI - Interleukin-1 beta upregulates cardiac expression of vascular endothelial growth
factor and its receptor KDR/flk-1 via activation of protein tyrosine kinases.
AB - Vascular endothelial growth factor (VEGF) is not only an endothelial cell
specific angiogenic factor but also a potent mediator of vascular permeability.
Interleukin-1 beta (IL-1 beta) is a pro-inflammatory cytokine that has numerous
effects on the pathogenesis of the tissue injury. To explore the possible
regulation of the VEGF system by IL-1 beta in the heart, we examined the
regulation of expression of VEGF and KDR/flk-1 (one of the VEGF receptors) by IL
1 beta using cardiac myocytes and cardiac microvascular endothelial cells (CMEC).
Both cardiac myocytes and CMEC substantially expressed VEGF mRNA and its
expression was increased 3.6- and 2.4-fold by IL-1 beta, respectively. IL-1 beta
induced accumulations of VEGF mRNA in cardiac myocytes were abolished by the
tyrosine kinase inhibitor genistein, whereas inhibition of protein kinase C (PKC)
by staurosporin, calphostin C and phorbol ester-induced PKC depletion, and
intracellular Ca2+ chelators did not affect the induction of VEGF mRNA by IL-1
beta. Relatively smaller amounts of KDR/flk-1 mRNA were detected in CMEC, but not
in cardiac myocytes, and the analysis using quantitative reverse transcription
polymerase chain reaction revealed that IL-1 beta significantly stimulated the
accumulation of KDR/flk-1 mRNA 3.0-fold. VEGF protein (23 kDa) levels in Western
blot analysis were increased 4.2- and 3.4-fold by IL-1 beta in cardiac myocytes
and CMEC, respectively. KDR/flk-1 protein (230 kDa) levels in CMEC were also
increased 3.2-fold by IL-1 beta. In addition, pre-treatment of CMEC by IL-1 beta
markedly enhanced VEGF-induced tyrosine phosphorylation of focal adhesion kinase
compared with that in the unstimulated cells. These findings indicate that
cardiac VEGF-KDR/flk-1 system is upregulated by IL-1 beta via activation of
tyrosine kinases, suggesting that the IL-1 beta-modulated autocrine and/or
paracrine system of VEGF has an important role in the process of angiogenesis in
ischemic hearts.
PMID- 10198192
TI - Sustained pulsatile flow regulates endothelial nitric oxide synthase and
cyclooxygenase expression in co-cultured vascular endothelial and smooth muscle
cells.
AB - This study addresses the effect of sustained increased pulsatile flow on nitric
oxide synthase (NOS) and cyclooxygenase (Cox) expression and activity in co
cultured endothelial cells (EC) and vascular smooth muscle cells (SMC). Using a
perfused transcapillary co-culture system which permits the chronic exposure of
cultured EC and SMC to physiological shear stresses, co-cultures were exposed to
step-wise increases in flow up to: (i) 2 ml/min (low flow: 0.5 dyn/cm2): or (ii)
44 ml/min (high flow: 15 dyn/cm2) and maintained for 72 h before SMC and EC were
harvested separately. There was no NOS activity or protein expression in co
cultured SMC under flow conditions. There was a significant increase in eNOS
activity in co-cultured EC under high flow conditions, compared to low flow,
which correlated with an increase in eNOS expression and mRNA levels. The flow
induced increase in eNOS activity was potentiated by indomethacin treatment,
suggesting a modulatory role for a cyclooxygenase product. Prostacyclin levels in
co-culture perfusate were significantly elevated under high flow conditions.
While both co-cultured EC and SMC expressed cyclooxygenase (Cox-I and Cox-II),
they were differentially regulated by pulsatile flow, EC Cox-I and Cox-II protein
expression were both decreased. Indomethacin treatment increased the expression
of both Cox-I and Cox-II in co-cultured SMC under high flow conditions. We
conclude that sustained increases in pulsatile flow maintain elevated eNOS and
Cox protein expression and activity in EC while decreasing Cox expression in co
cultured SMC. These data suggest that regulation of these pathways may contribute
to flow-induced vascular remodeling in vivo.
PMID- 10198193
TI - Effects of endothelin-1 on Ca2+ signaling in guinea-pig ventricular myocytes:
role of protein kinase C.
AB - The effects of ET-1 on contraction, Ca2+ transient and L-type Ca2+ current
(ICa.L) were studied in single cells isolated from ventricles of guinea-pig
hearts. The aim of our study was to elucidate the mechanism of the positive
inotropic effect during endothelin receptor stimulation by focusing on the role
of PKC. ET-1 at concentrations of 5 and 10 nM produced a biphasic pattern of
inotropism: a first decrease in contraction by 34.4 +/- 2.5% of the control
followed by a sustained increase in contraction by 66.6 +/- 8.4% (mean +/- SEM, n
= 9). The Ca2+ transient decreased by 13.5 +/- 1.0% during the negative inotropic
phase, while it increased by 58.1 +/- 8.4% (n = 10) during the positive inotropic
phase. Using the whole-cell voltage-clamp technique with conventional
microelectrodes, the application of ET-1 (5 nM) increased the ICa.L by 32.6 +/-
5.1% (n = 10), which was preceded by a short-lived decrease in ICa.L. Incubation
of myocytes with pertussis toxin (PTX, at 2 micrograms/ml for > 3 h at 35 degrees
C) failed to block the ET-1-induced enhancement of ICa.L. The increases in
contraction, Ca2+ transient, and ICa.L by ET-1 were inhibited by pretreatment
with 5-N-methyl-N-isobutyl amiloride (MIA; 10 microM), an amiloride analog, and a
novel selective Na+/H+ exchange inhibitor HOE694 (10 microM). To determine
whether activation of protein kinase C (PKC) is responsible for the enhancement
of ICa.L by ET-1, we tested a PKC inhibitor, GF109203X, and found that it does
exert an inhibitory effect on the ET-1-induced ICa.L increase. Our study suggests
that during ET receptor stimulation an increase in ICa.L due to stimulation of
Na+/H+ exchange via PKC activation causes an increase in Ca2+ transients and
thereby in the contractile force of the ventricular myocytes.
PMID- 10198194
TI - Thyroid hormone control of contraction and the Ca(2+)-ATPase/phospholamban
complex in adult rat ventricular myocytes.
AB - Thyroid hormones may have important long-term effects on cellular Ca2+ handling
in the heart. We investigated isolated adult rat cardiomyocytes in a primary
culture exposed (T3-cells) or not exposed to (control cells) 10(-8) M
triiodothyronine (T3) for 48 h. Northern blot analysis revealed reciprocal
alterations in the expression of SERCA2 and phospholamban. The ratio of the
SERCA2/phospholamban signal was approximately 10 times higher in the T3-cells as
compared with the control cells (P < 0.05). Phospholamban protein content was
significantly reduced by 33% but SR-Ca(2+)-ATPase protein content was not
significantly altered in T3-cells. These results were associated with functional
alterations measured by an inverted microscope equipped to monitor fluorescence
at two excitation wavelengths as well as cell shortening by a video edge
detection unit. The peak calcium transients as measured by fura-2 acetoxymethyl
ester (AM) were increased significantly during stimulation at 0.25 and 0.5 Hz in
T3-cells compared with control cells (P < 0.05). The monoexponential decline of
the fura-2 transient was significantly faster at all frequencies in the T3-cells
as compared with control cells (P < 0.05). Interestingly, we observed blunted
responses to both isoproterenol stimulation and post rest potentiation in the T3
cells. The intracellular level of sodium as represented by SBFI-AM was
significantly lower in the T3-cells compared with the control cells (P < 0.05).
The increased SR-Ca(2+)-ATPase/phospholamban ratio and decrease in phospholamban
protein content in T3-treated cells was reflected in a parallel increase of
contraction and calcium transients and more rapid Ca2+ reuptake, but the post
rest potentiation and response to isoproterenol were reduced.
PMID- 10198195
TI - Expression of CLCN voltage-gated chloride channel genes in human blood vessels.
AB - Chloride (Cl) ion channels play a critical role in the response of both vascular
smooth muscle (VSM) and endothelial (ENDO) cells to agonist stimulation. In VSM,
agonist-induced Cl currents produce membrane depolarization, resulting in calcium
influx through voltage-sensitive channels. ENDO cells also activate Cl currents
after either agonist application or perturbation of cell volume. Although some of
these currents have been characterized biophysically, the genes involved have not
been identified. The CLCN family of voltage-dependent Cl channel genes comprises
nine members (CLCN1-7, Ka and Kb) which demonstrate quite diverse functional
characteristics while sharing significant sequence homology. We used Northern
blot analysis to study the expression of these Cl channel genes in cultured human
aortic and coronary VSM cells and in aortic ENDO cells. CLCN3 is by far the most
abundant CLC channel mRNA in both VSM and ENDO cells. Lower levels of expression
are seen for CLCN2, CLCN4, CLCN5 and CLCN6. Expression levels were similar in VSM
and ENDO cells except for CLCN4 which was more highly expressed in ENDO cells. In
situ hybridization was used to confirm the expression of CLCN3 in intact human
fetal lung. CLCN3 message was seen in VSM and ENDO cells of both large and small
pulmonary vessels, indicating that their detection by Northern blotting was not
an artifact of cell culture. CLCN3 is also expressed in pulmonary epithelial and
bronchial smooth muscle cells but not in chondrocytes or pulmonary interstitial
cells. Recent studies suggest that CLCN3 may encode the swelling-induced Cl
conductance. We used whole cell patch clamp recording to demonstrate swelling
induced Cl currents in these cultured VSM cells. This suggests that the CLCN3
protein is expressed; however, the functional role of this current in VSM remains
to be determined.
PMID- 10198196
TI - Elevation of expression of Smads 2, 3, and 4, decorin and TGF-beta in the chronic
phase of myocardial infarct scar healing.
AB - We have previously shown that non-myocytes present in healed 8-week infarct scar
overexpress transduction proteins required for initiating the elevated deposition
of structural matrix proteins in this tissue. Other work suggests that TGF-beta 1
may be involved in cardiac fibrosis and myocyte hypertrophy. However, the
significance of the altered TGF-beta signaling in heart failure in the chronic
phase of post-myocardial infarction (MI), particularly in the ongoing remodeling
of the infarct scar, remains unexplored. Patterns of cardiac TGF beta 1 and Smad
2, 3, and 4 protein expression were investigated 8 weeks after MI and were
compared to relative collagen deposition in border tissues (containing remnent
myocytes) and the infarct scar (non-myocytes). Both TGF-beta 1 mRNA abundance and
protein levels were significantly increased in the infarct scar v control values,
and this trend was positively correlated to increased collagen type I expression.
Cardiac Smad 2, 3, and 4 proteins were significantly increased in border and scar
tissues v control values. Immunofluorescent studies indicated that Smad proteins
localized proximal to the cellular nuclei present in the infarct scar. Decorin
mRNA abundance was elevated in border and infarct scar, and the pattern of
decorin immunostaining was markedly altered in remote remnant heart and scar v
staining patterns of control sections. Expression of T beta RI (53 kDa) protein
was significantly reduced in the scar, while the 75 kDa and 110 kDa isoforms of T
beta RII were unchanged and significantly increased in scar, respectively. These
results indicate that TGF-beta/Smad signaling may be involved in the remodeling
of the infarct scar after the completion of wound healing per se, via ongoing
stimulation of matrix deposition.
PMID- 10198197
TI - The human phospholamban gene: structure and expression.
AB - Phospholamban, through modulation of sarcoplasmic reticulum calcium-ATPase
activity, is a key regulator of cardiac diastolic function. Alterations in
phospholamban expression may define parameters of muscle relaxation. In
experimental animals, phospholamban is differentially expressed in various
striated and smooth muscles, and within the four chambers of the heart. Decreased
phospholamban expression within the heart during heart failure has also been
observed. Furthermore, regulatory elements of mammalian phospholamban genes
remain poorly defined. To extend these studies to humans, we (1) characterized
phospholamban expression in various human organs, (2) isolated genomic clones
encoding the human phospholamban gene, and (3) prepared human phospholamban
promoter/luciferase reporter constructs and performed transient transfection
assays to begin identification of regulatory elements. We observed that human
ventricle and quadriceps displayed high levels of phospholamban transcripts and
proteins, with markedly lower expression observed in smooth muscles, while the
right atria also expressed low levels of phospholamban. The human phospholamban
gene structure closely resembles that reported for chicken, rabbit, rat, and
mouse. Comparison of the human to other mammalian phospholamban genes indicates a
marked conservation of sequence for at least 217 bp upstream of the transcription
start site, which contains conserved motifs for GATA, CP1/NFY, M-CAT-like, and E
box elements. Transient transfection assays with a series of plasmids containing
deleted 5' flanking regions (between -2530 and -66 through +85) showed that
sequences between -169 and the CP1-box at -93 were required for maximal promoter
activity in neonatal rat cardiomyocytes. Activity of these reporters in HeLa
cells was markedly lower than that observed in rat cardiomyocytes, suggesting at
least a partial tissue selectivity of these reporter constructs.
PMID- 10198198
TI - Amadorins: novel post-Amadori inhibitors of advanced glycation reactions.
AB - The present review focuses on the background and progress that led to discovery
of specific inhibition of post-Amadori formation of advanced glycation end
products, or AGEs. The "classic" or Hodge pathway begins with glucose
condensation with amino groups to form a Schiff base aldimine adduct that
undergoes rearrangement to a ketoamine Amadori product. This pathway is
considered an important route to AGE formation that has been implicated in
glucose-mediated damage in vivo (3-5). We recently described a facile procedure
for isolation of proteins rich in Amadori adducts but free of AGEs, thus
permitting study of pathways of conversion of Amadori compounds to AGEs. This in
turn led to a unique and rapid post-Amadori screening assay for putative
"Amadorins," which we define here as inhibitors of the conversion of Amadori
intermediates to AGEs in the absence of excess free or reversibly bound (Schiff
base) sugar. Our screening assay then led to the identification of pyridoxamine
(Pyridorin) as the first member of this class of Amadorin compounds. Rather
unexpectedly, the assay also led to the clear demonstration that the well-known
AGE inhibitor aminoguanidine, currently in Phase 3 clinical trials for treatment
of diabetic nephropathy, has negligible Amadorin activity. In view of the
importance of Amadori compounds as intermediates in AGE formation in vivo, the
therapeutic potential of Pyridorin is currently being investigated and is now
showing highly promising results in different animal models.
PMID- 10198199
TI - Expression of dioxin-responsive genes in human endometrial cells in culture.
AB - To investigate expression of dioxin-responsive genes in human endometrial cells
with exposure to 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD), human endometrial
stromal cells immortalized with temperature-sensitive SV40 T antigen were used
for the experiments. Cells were treated with 0.1% DMSO or 0.1, 1, 10, or 100 nM
TCDD for 24 h. Induction of interleukin-1beta (IL-1beta) and plasminogen
activator inhibitor-2 (PAI-2) mRNAs was analyzed by reverse-transcription
polymerase chain reaction. Expression of IL-1beta or PAI-2 mRNA in response to
TCDD was increased in a dose-dependent fashion. The maximum increases of PAI-2
and IL-1beta mRNAs were observed at 100 and 10 nM TCDD, respectively. While
cycloheximide treatment did not show a significant difference of PAI-2 mRNA
levels between control and TCDD-treated cells, mRNA stability assay using
actinomycin D showed that PAI-2 mRNA in TCDD-treated cells was about twofold more
stable than the control cells. While expression of CYP1A1 mRNA was not detected
and levels of ARNT mRNA were not altered by TCDD exposure, the amount of AhR mRNA
was decreased dose dependently. The present study represents an initial attempt
to determine the responses of dioxin-responsive genes in human endometrial cells
following TCDD exposure. The results demonstrated that IL-1beta and PAI-2 genes
are induced dose dependently in human endometrial cells with exposure to TCDD and
expression of PAI-2 mRNA is controlled at the posttranscriptional level.
PMID- 10198200
TI - Distribution and characterization of immunoreactive prolactin-releasing peptide
(PrRP) in rat tissue and plasma.
AB - We established a sensitive and specific two-site enzyme immunoassay (EIA) for
prolactin-releasing peptide (PrRP) using two region-specific monoclonal
antibodies. We investigated the tissue distribution and the plasma concentration
of immunoreactive (ir-) PrRP in rats using this assay. Ir-PrRP was widely
distributed in the central nervous system and pituitary gland. The highest
concentration of ir-PrRP was found in the hypothalamus. In peripheral tissues,
appreciable levels of ir-PrRP were found only in the adrenal gland. The mean
plasma concentration of ir-PrRP was 0.13 +/- 0.01 fmol/ml (mean +/- SEM). In
reverse-phase and gel-filtration high performance liquid chromatography,
hypothalamic ir-PrRP eluted at a position identical to that of PrRP31 and PrRP20.
On the other hand, ir-PrRP from the adrenal gland and plasma eluted only at the
position of synthetic PrRP31, indicating that molecular forms of ir-PrRP in vivo
differed among tissues.
PMID- 10198201
TI - The pest regions containing C-termini of mammalian ornithine decarboxylase and
histidine decarboxylase play different roles in protein degradation.
AB - Proteasome 26S must recognize the PEST region-containing C-terminus of mammalian
ornithine decarboxylase (ODC) monomer to proceed with degradation. We have
detected PEST regions in both termini of mammalian histidine decarboxylase (HDC).
In the present report, a chimaeric ODC/HDC was used to elucidate whether the PEST
region-containing C-termini of ODC and HDC are exchangeable. Wild-type rat ODC
had an expected antizyme and ATP-dependent degradation. This was not the case for
both the chimaera and a C-terminus truncated rat ODC. Results suggest that the
PEST region-containing C-terminus of rat HDC should have another role different
to confering polypeptide availability to the proteasome.
PMID- 10198202
TI - Electrostatic interaction between cytochrome P450 and NADPH-P450 reductase:
comparison of mixed and fused systems consisting of rat cytochrome P450 1A1 and
yeast NADPH-P450 reductase.
AB - The electrostatic interaction between rat cytochrome P450 1A1 and yeast NADPH
P450 reductase was analyzed by using recombinant yeast microsomes containing both
native enzymes or their fused enzyme. The Vmax of the 7-ethoxycoumarin O
deethylation in the recombinant microsomes containing both rat cytochrome P4501A1
and yeast NADPH-P450 reductase (the mixed system) was maximal when the ionic
strength of the reaction mixture was 0.1-0.15. However, on the fused enzyme
between rat cytochrome P450 1A1 and yeast NADPH-P450 reductase (the fused
system), the activity was uniformly reduced with increasing ionic strength. The
pH profiles of Vmax were also different between the mixed and the fused systems.
Based on these results, we propose a hypothesis that cytochrome P450 and NADPH
P450 reductase have more than one binding mode. The maximal activity of the mixed
system at ionic strength of 0.1-0.15 is explained by change of the binding mode.
On the other hand, the fused enzyme appears to have only one binding mode due to
the limited topology of cytochrome P450 and NADPH-P450 reductase domains.
PMID- 10198204
TI - Genomic organization of human myristoyl-CoA: protein N-myristoyltransferase-1.
AB - Myristoylation is a biochemical modification of proteins in which the lipid
myristate becomes covalently bound to various cellular, viral, and oncoproteins
catalyzed by a monomeric enzyme myristoyl-CoA:protein N-myristoyltransferase
(NMT). This modification is important for the biological activity of several
proteins, especially the regulation of several oncoproteins involved in various
types of cancers. Complementary DNA encoding human NMT-1 (hNMT-1) has been
previously reported; however, the genomic organization of hNMT-1 has not been
available. Attempts to amplify genomic fragments corresponding to hNMT-1 cDNA
sequence yielded only one fragment. We have searched databases using both the
cDNA and sequence of one of the intron sequence and this identified a human BAC
clone sequence from chromosome 17. Alignment of hNMT-1 cDNA coding information on
human chromosome 17 resulted in the complete structural identity of 23,960 bp of
the hNMT-1 gene. The hNMT-1 gene is composed of 11 exons and 10 introns with
consensus GT/AG boundaries. Finally, we show that 140 bp from the 5' end of
recently reported full-length cDNA of hNMT-1 was not part of this genomic region
raising the possibility for posttranscriptional modification in generating larger
transcripts likely by trans splicing. Further, the availability of this genomic
sequence will assist in unraveling the molecular basis for several observed NMT
isoforms.
PMID- 10198203
TI - Regulation of the reduced-folate transporter by nitric oxide in cultured human
retinal pigment epithelial cells.
AB - The regulation of the reduced-folate transporter (RFT) by nitric oxide (NO) was
analyzed in human retinal pigment epithelial (HRPE) cells. NO inhibited
specifically and reversibly the uptake of N5-methyltetrahydrofolate by a cGMP
independent mechanism. The inhibition was associated with a decrease in substrate
affinity. The NO-induced inhibition was prevented by antioxidants and NO
scavengers. Agents capable of modifying thiol groups in proteins inhibited RFT,
indicating that the likely mechanism of NO-induced inhibition is via modification
of essential thiol groups in this protein. These studies suggest that NO produced
during retinal disease may affect the function of RFT in adjacent RPE cells.
PMID- 10198205
TI - Unidirectional transport from apical to basolateral compartment of cobalt ion in
polarized Madin-Darby canine kidney cells.
AB - Renal transport of Co2+ was studied by use of cultured MDCK cells with cell
polarity. Cells imported 57Co2+ from the apical membrane exclusively, while
uptake from the basolateral membrane was minute. Apical uptake was time-,
concentration-, pH-, and temperature- dependent and the dose-dependency curve was
saturable, indicating that a carrier-mediated influx process operates in the
apical membrane. The substrate specificity and other properties of this Co2+
transport process are distinct from those of a transporter DCT1, divalent cation
transporter 1, with unusually broad substrate specificity including Co2+.
Radioactive Co2+ added from the apical side appeared in the basolateral side,
while there was only slight movement of Co2+ from the basolateral to apical side,
indicating that this unidirectional transepithelial passage of Co2+ is not caused
by the paracellular diffusion, but by the basolateral export of the cellular Co2+
uptake from the apical membrane. Our results may indicate the presence of a novel
vectorial transport system responsible for the reabsorption of Co2+ from the
glomerular filtrate.
PMID- 10198206
TI - Assignment of disulfide linkages in chum salmon stanniocalcin.
AB - Stanniocalcin (STC) is a hypocalcemic glycoprotein hormone secreted by the
corpuscles of Stannius, endocrine glands unique to the bony fishes. Recently, two
cDNAs encoding proteins, STC-1 and STC-2, homologous to fish STC have been
identified in humans and rodents. The STC-1, but not STC-2, is identical to fish
STC with respect to location of all Cys residues. The present study reports the
localization of inter- and intra-molecular disulfide linkages in chum salmon STC.
The chum salmon STC was deglycosylated and digested with several proteases in
series. Six fragments, each of which consisted of two peptides connected by a
single disulfide bond, were isolated by HPLC. Disulfide bonds were determined by
sequence analysis after reduction and S-alkylation of each peptide fragment. Chum
salmon STC is a homodimer connected by a single intermonomeric disulfide bond at
Cys169. The monomer consists of 179 amino-acids, containing five intramonomeric
disulfide bonds formed between Cys12-Cys26, Cys21-Cys41, Cys32-Cys81, Cys65
Cys95, and Cys102-Cys137.
PMID- 10198207
TI - The map1 gene of Cowdria ruminantium is a member of a multigene family containing
both conserved and variable genes.
AB - Heartwater is an economically important disease of ruminants caused by the tick
transmitted rickettsia Cowdria ruminantium. The disease is present in Africa and
the Caribbean and there is a risk of spread to the Americas, particularly because
of a clinically asymptomatic carrier state in infected livestock and imported
wild animals. The causative agent is closely related taxonomically to the human
and animal pathogens Ehrlichia chaffeensis and Ehrlichia canis. A dominant immune
response of infected animals or people is directed against variable outer
membrane proteins of these agents known, in E. chaffeensis and E. canis, to be
encoded by polymorphic multigene families. We demonstrate, by sequence analysis,
that map1 encoding the major outer membrane protein of C. ruminantium is also
encoded by a polymorphic multigene family. Two members of the gene family are
located in tandem in the genome. The upstream member, orf2, is conserved,
encoding only 2 amino acid substitutions among six different rickettsial strains
from diverse locations in Africa and the Caribbean. In contrast, the downstream
member, map1, contains variable and conserved regions between strains.
Interestingly, orf2 is more closely related in sequence to omp1b of E.
chaffeensis than to map1 of C. ruminantium. The regions that differ among orf2,
map1, and omp1b correspond to previously identified variable sequences in outer
membrane protein genes of E. chaffeensis and E. canis. These data suggest that
diversity in these outer membrane proteins may arise by recombination among gene
family members and offer a potential mechanism for persistence of infection in
carrier animals.
PMID- 10198208
TI - Nicotine regulates basic fibroblastic growth factor and transforming growth
factor beta1 production in endothelial cells.
AB - Nicotine, a constituent of cigarette smoking, may induce atherosclerosis through
the production of growth factors. The pattern of bFGF and TGF beta1 production
and release by bovine aortic endothelial cells (EC) stimulated with nicotine
(from 6 x 10(-4) to 6 x 10(-8) M) was studied. EC viability and count were
assessed. The presence of bFGF and TGF beta1 in serum-free conditioned media was
determined by the inhibition antibody-binding assay and Western blot analysis.
Mitogenic activity of nicotine on EC was also determined. Polymerase chain
reaction (PCR) was used to study the expression of bFGF and TGF beta1. The bFGF
release after nicotine stimulation was greater than controls, whereas TGF beta1
release was lower. At a nicotine concentration of 6 x 10(-6) M we noted the
greatest mitogenic activity. The addition of monoclonal antibody anti-bFGF
decreased the tritiated thymidine uptake of EC exposed to nicotine but the
addition of monoclonal antibody anti-TGF beta1 had no significant effect. bFGF
mRNA expression was significantly higher in EC exposed to nicotine than in
controls, whereas TGF beta1 mRNA expression was not modified. From these data we
concluded that nicotine regulates bFGF production and release and TGF beta1
release and may have a key role in the development and progression of
atherosclerosis.
PMID- 10198209
TI - Full-length cDNA of human cathepsin F predicts the presence of a cystatin domain
at the N-terminus of the cysteine protease zymogen.
AB - A novel human cDNA encoding a cysteine protease of the papain family named
cathepsin F is reported. The mature part of the predicted protease precursor
displays between 26% and 42% identity to other human cysteine proteases while the
proregion is unique by means of length and sequence. The very long proregion of
the cathepsin F precursor (251 amino acid residues) can be divided into three
regions: a C-terminal domain similar to the pro-segment of cathepsin L-like
enzymes, a 50 residue flexible linker peptide, and an N-terminal domain predicted
to adopt a cystatin-like fold. Cathepsin F would therefore be the first cysteine
protease zymogen containing a cystatin-like domain.
PMID- 10198210
TI - Genotoxicity of human milk extracts and detection of DNA damage in exfoliated
cells recovered from breast milk.
AB - Genotoxic agents of environmental or dietary origin may play a role in breast
cancer initiation. The ability of extracts of human milk to cause mutations in S.
typhimurium TA1538 and YG1019 and to induce micronuclei and DNA strand breaks in
MCL-5 cells was investigated. Twenty samples from different donors were analysed
and of these, 6 were adjudged to produce a positive mutagenic response in one or
both bacterial strains. The same samples also induced significant micronucleus
formation in MCL-5 cells. In the comet assay, 13/20 samples caused DNA strand
breaks in MCL-5 cells. Viable exfoliated breast cells were recovered from fresh
milk samples and the ability of milk extracts to cause DNA damage in these cells
was demonstrated. The results show that human milk can contain components capable
of causing genotoxic damage in test systems and in human breast cells, events
that may be significant in the initiation of breast cancer.
PMID- 10198211
TI - S-form lipopolysaccharide (LPS), but not lipid A or R-chemo-type LPS, induces
interleukin-6 production in vitamin D3-differentiated THP-1 cells.
AB - Bacterial lipopolysaccharide (LPS) induces the production of various inflammatory
cytokines and the inducibility is considered attributable to the glycolipid part
of LPS called lipid A. We report an in vitro model in which lipid A is not
necessarily a minimal structure for the LPS activity. Vitamin D3-differentiated
THP-1 cells, cultured human monocytic leukemia cells, produced a high level of
interleukin-6 (IL-6) by stimulating LPS from Escherichia coli O111:B4, but not by
stimulating synthetic E. coli-type lipid A (compound 506), E. coli Re mutant LPS
(ReLPS), or alkali-treated LPS. The induction by LPS was inhibited by the anti
CD14 antibodies or by the synthetic lipid A precursor (compound 406). An alkali
treated LPS or compound 506 partially inhibited the LPS-induced IL-6 production.
These facts suggest that lipid A alone is not sufficient for the IL-6-inducing
activity, but the polysaccharide part in LPS contributes or acts as a co-factor
for activation of differentiated THP-1 cells.
PMID- 10198212
TI - Cloning, expression, and chromosomal mapping of a human ATPase II gene, member of
the third subfamily of P-type ATPases and orthologous to the presumed bovine and
murine aminophospholipid translocase.
AB - Recently, a P-type ATPase was cloned from bovine chromaffin granules (b-ATPase
II) and a mouse teratocarcinoma cell line (m-ATPase II) and was shown to be
homologous to the Saccharomyces cerevisiae DRS2 gene, the inactivation of which
resulted in defective transport of phosphatidylserine. Here, we report the
cloning from a human skeletal muscle cDNA library of a human ATPase II (h-ATPase
II), orthologous to the presumed bovine and mouse aminophospholipid translocase
(95.3 and 95.9% amino acid identity, respectively). Compared with the bovine and
mouse counterparts, the cloned h-ATPase II polypeptide exhibits a similar
membrane topology, but contains 15 additional amino acids (1163 vs 1148) located
in the second intracytoplasmic loop, near the DKTGTLT-phosphorylation site.
However, RT-PCR analysis performed with RNA from different human tissues and cell
lines revealed that the coding sequence for these 15 residues is sometimes
present and sometimes absent, most likely as a result of a tissue-specific
alternative splicing event. The h-ATPase II gene, which was mapped to chromosome
4p14-p12, is expressed as a 9.5-kb RNA species in a large variety of tissues, but
was not detected in liver, testis, and placenta, nor in the erythroleukemic cell
line K562.
PMID- 10198213
TI - 73-kDa heat shock cognate protein interacts directly with P27Kip1, a cyclin
dependent kinase inhibitor, during G1/S transition.
AB - Although heat shock proteins (HSPs) were discovered as inducible proteins by the
physical stress to protect cells, recent evidence has suggested that HSPs are
likely involved in cell cycle control under normal conditions without stress. In
the present study, we demonstrated that 73hsc (heat shock cognate protein), which
belongs to the HSP70 family of molecular chaperones, interacts with P27Kip1, an
inhibitor of cyclin-dependent kinase, during G1/S transition. 73hsc was detected
in the immunoprecipitates with anti-P27Kip1 antibody and, vice versa, P27Kip1 was
present in the immunoprecipitates with anti-73hsc antibody by Western blotting
using growth-stimulated rat thyroid FRTL-5 cells. This complex formation of 73hsc
and P27Kip1 was cell cycle dependent and its maximum formation was observed at
G1/S transition where the level of P27Kip1 dramatically decreased. ATP
dissociated this complex formation in a dose-dependent manner. These data
indicated that 73hsc might be involved in the cell cycle progression through the
regulation of cell cycle regulators such as P27Kip1.
PMID- 10198214
TI - Stoichiometric arginine binding in the oxygenase domain of inducible nitric oxide
synthase requires a single molecule of tetrahydrobiopterin per dimer.
AB - In addition to its catalytic roles, the nitric oxide synthase (NOS) cofactor
tetrahydrobiopterin (H4B) is required for substrate binding and for stabilization
of the dimeric structure. We expressed and purified the core of the iNOS
oxygenase domain consisting of residues 75-500 (CODiNOS) in the presence (H4B+)
and absence (H4B-) of this cofactor. Both forms bound stoichiometric amounts of
heme (>0.9 heme per protein subunit). H4B- CODiNOS was unable to bind arginine,
gave an unstable ferrous carbonyl adduct, and was a mixture of monomer and dimer.
H4B+ CODiNOS bound arginine, gave a stable ferrous carbonyl adduct, and was
exclusively dimeric. The H4B cofactor content of this species was only one per
dimer yet this was sufficient to form two competent arginine binding sites as
determined by optical stoichiometric titrations.
PMID- 10198215
TI - Determination of mean and standard deviation of dihedral angles.
AB - Backbone torsional angles are a characteristic and useful parameter for the
description and characterisation of protein structures determined by x-ray
crystallography or NMR spectroscopy. For the comparison of an ensemble of three
dimensional structures the calculation of the statistical parameters mean and
standard deviation would be very useful. However, they are not defined
unambiguously for periodic quantities such as the dihedral angles. In this paper
a plausible and unique definition of these parameters is introduced and a
straightforward method for their calculation is given.
PMID- 10198216
TI - Changes in expression of the 44-kilodalton outer surface membrane antigen (p44
kD) for monitoring progression of infection and antimicrobial susceptibility of
the human granulocytic ehrlichiosis (HGE) agent in HL-60 cells.
AB - Changes in human granulocytic ehrlichiosis (HGE)-specific major outer membrane
protein (p44 kD) were assayed by Western blot analysis in HL-60 cells in vitro
infected by the HGE agent. Time course study demonstrated that the expression of
p44 preceded the rise in cell infection as determined by the presence of
intracellular morulae. To test whether the expression of p44 may be suitable for
evaluating the effects of antibiotics in vitro, three recent isolates of the HGE
agent were exposed to doxycycline and ampicillin during culture with HL-60 cells.
Loss of infection concurrent with disappearance of the 44 kD protein was found
with doxycycline treatment. In contrast, ampicillin treatment had no discernible
effects on infection or 44 kD expression. There was excellent agreement between
infection, as measured by morulae, and 44 kD expression (coefficient of
correlation r = 0.97, p < 0.01). Following treatment with doxycycline, the 44 kD
protein disappeared with an estimated t1/2 of approximately 24-30 h, which was
considerably shorter than a t1/2 of >60 h calculated for loss of morulae.
Measurement of p44 expression may be a more rapid and simple assay to determine
antibiotic susceptibility of the HGE agent in cell culture. Furthermore, it may
be used to indicate the presence of infection before morulae are apparent.
PMID- 10198217
TI - Hairpin ribozyme specificity in vivo: a case of promiscuous cleavage.
AB - We have used differential display to address the question of ribozyme specificity
in vivo. Stably transfected PC12 cells bearing either a hairpin ribozyme
expression plasmid targeted to betaAPP mRNA or the vector alone were analyzed
using nine different primer pairs. One of the few differentially expressed genes
obtained from this screen corresponded to rat ribosomal protein L19. Steady-state
levels of L19 mRNA were lower in ribozyme-transfected cells compared to either
vector-transfected cells or native PC12 cells, and a sequence within the L19
message was cleaved by the betaAPP hairpin ribozyme in vitro. These data imply
that sequence-specific unintended cleavage of non-target mRNAs may present a
formidable problem to the use of hairpin ribozyme therapeutic agents.
PMID- 10198218
TI - Increased sensitivity of human colon cancer cells to DNA cross-linking agents
after GRP78 up-regulation.
AB - We have shown earlier that pre-treatment of V79 Chinese hamster cells with 6
aminonicotinamide (6-AN) or 2-deoxyglucose (2-dG) results in over-expression of
the Mr 78,000 glucose-regulated stress protein (GRP78) and the subsequent
development of resistance to inhibitors of topoisomerase II. These phenomena also
occur in V79-derived cell lines that are deficient in poly(ADP-ribose) (p(ADPR))
metabolism. In contrast, over-expression of GRP78 under the conditions outlined
above is found to be associated with hypersensitivity to several clinically
relevant DNA cross-linking agents, namely, 1,3-bis (2-chloroethyl)-1-nitrosourea
(BCNU), cisplatin, and melphalan. We have also previously shown that pre
treatment with 6-AN, an inhibitor of p(ADPR) metabolism, causes an increase in
the life span in BCNU-treated mice bearing L1210 tumors. These observations
prompted us to examine whether 6-AN pre-treatment can result in the over
expression of GRP78 in human colon cancer cell lines and, if so, whether this
increase is associated with sensitization to DNA cross-linking agents outlined
above. Following treatment of three colon cancer cell lines, HCT116, SW480, and
VACO-8, for 48 h with 0.1 mM 6-AN, cytosolic GRP78 levels were elevated
approximately 4.2 times, 8 times, and 2.5 times for each cell line respectively,
as measured by Western immunoblotting. To determine sensitivity after GRP78 up
regulation, the cells were washed and grown for 412 h in growth medium devoid of
6-AN, before being treated with DNA cross-linking agents. The 412 h time period
allowed p(ADPR) metabolism to return to normal while GRP78 levels remained
elevated, thus allowing us to associate GRP78 over-expression with sensitivity to
those agents. After treating cells for 1 h with BCNU, cisplatin, or melphalan,
cell sensitivity was determined by clonogenic survival assay or a fluorescence
based cytotoxicity assay. Based on changes in IC50 values, 6-AN caused an
increase in sensitivity for HCT116, SW480, and VACO-8 cells of 1.5, 2.3, and 1.0
times, respectively, for BCNU, 4.8, 3.8, and 2.6 for cisplatin, and 6.4, 3.7, and
2.2 times for melphalan. Thus, our results show that over-expression of GRP78 in
human tumor cell lines is associated with increased sensitivity to clinically
useful chemotherapy agents. This sensitization occurred in three different tumor
cell lines, each bearing a separate genetic defect associated with altered
sensitivity.
PMID- 10198219
TI - Biochemical localisation of the 5-HT2A (serotonin) receptor in rat skeletal
muscle.
AB - The 5-HT2A receptor was recently shown to localise morphologically to the
transverse tubules (TT) in rat foetal myoblasts. Receptor activation enhanced the
expression of genes involved in myogenesis, and its TT localisation has led to
the suggestion that it may participate in excitation-contraction coupling. In
order to gain further insights into 5-HT2A receptor function in muscle we have
(i) investigated its biochemical localisation in adult rat skeletal muscle and
(ii) determined whether receptor expression is dependent upon muscle type.
Immunoblot analysis of muscle membranes, isolated by subcellular fractionation,
revealed that adult muscle expresses the 5-HT2A receptor and that it resides
exclusively in plasma membranes and not in TT. No differences in 5-HT2A abundance
were observed between red and white muscle, suggesting that receptor expression
does not correlate with the metabolic or contractile properties of the muscle
fibre. Our data indicate that 5-HT2A expression in skeletal muscle is maintained
into adulthood and that its absence from TT make it an unlikely participant in
the excitation-contraction coupling process.
PMID- 10198220
TI - Role of endothelin-1 and interleukin-4 in buccal mucosal ulcer healing: effect of
chronic alcohol ingestion.
AB - We investigated the effect of chronic alcohol ingestion on buccal mucosal ulcer
healing by analyzing the interplay between mucosal expression of tumor necrosis
factor-alpha (TNF-alpha), endothelin-1 (ET-1), and interleukin-4 (IL-4). Chronic
ulceration was induced in rats maintained for 5 weeks on alcohol-containing or
control liquid diet. In both groups, the ulcer onset was characterized by a
massive increase (6.5-8.9-fold) in TNF-alpha and ET-1 (1.6-4.0-fold), and a
decrease (1.4-1.5-fold) in IL-4. However, the group on the alcohol diet exhibited
a 38.3% higher mucosal expression of TNF-alpha, a 26. 2% higher ET-1 level, and a
6.5% lower content of IL-4. While in both groups the ulcer healing was
accompanied by an increase in buccal mucosal expression of IL-4, and a decline in
ET-1 and TNF-alpha, the changes were significantly slower in the alcohol diet
group and manifested by a 4 day delay in ulcer healing. The results suggest that
chronic alcohol ingestion exerts detrimental effects on the buccal mucosal IL-4
expression, causing dysregulation of ET-1 production, induction of TNF-alpha, and
triggering apoptotic events that delay the mucosal repair.
PMID- 10198221
TI - Focal sites of DNA repair synthesis in human chromosomes.
AB - Nucleotide excision repair (NER) is the principle pathway by which the human
cells eliminate UV-induced lesions from their genomic DNA. The process can be
visualized through the labelling of the nucleotides that are incoporated into
repair patches, following the excision of the damaged stretch of DNA. In this
study we have visualized sites of DNA repair synthesis (DRS) in human interphase
and metaphase chromosomes after very short times (2.5-30 min) of postirradiation
labelling in vivo with 5-iododeoxyuridine. A limited number (<50 per nucleus) of
discrete nuclear DRS sites were seen in cells fixed immediately after labelling
and the sites are also detectable in interphase and metaphase chromosomes
visualized 48h after irradiation (3 J/m2). These observations strongly support
the view that within a given short time window distinct chromosome domains are
under extensive repair while in many other domains NER is slow. They argue
against the general distributative NER process but are consistent with a
processive scanning of damaged domains.
PMID- 10198222
TI - Effects of missense mutations and deletions on membrane anchoring and enzyme
function of human steroid 21-hydroxylase (P450c21).
AB - We studied membrane binding and enzyme function of six variant forms of human
steroid 21-hydroxylase (P450c21), a mutant (P30Q) from a patient with congenital
adrenal hyperplasia, four artificial deletions in the amino terminal region
(delS1 and del S2; the first and second hydrophobic segment, delS3; the region in
between, delS4; the combination of these), and one naturally ocurring
polymorphism in a region implicated to be critical for membrane integration
(delL10). Enzyme function was assayed after transient expression in COS-1 cells,
and membrane binding was studied by coupled in vitro transcription-translation in
the presence of microsomal membranes. P450c21(delS1) retained some enzyme
activity but showed severely reduced membrane binding. P450c21(P30Q), P450c21
(delS2), P450c21(delS3), and P450c21(delS4) had abolished enzyme function.
P450c21(P30Q) and P450c21 (delS2) did not affect membrane binding, P450c21
(delS3) had slightly reduced binding with a qualitative difference suggested by
the absence of a glycosylated form of the protein, and P450c21(delS4) had
abolished membrane integration. No significant differences could be identified
for the delL10 variant. These data support that P450c21 spans the membrane
through its first hydrophobic domain only, and that the protein lacking this
segment retains sufficiently normal structure to enable catalysis. They also
confirm that P30Q is responsible for the severe phenotype of the patient in which
it was found, and indicate that the common delL10 polymorphism does not have a
major effect on enzyme function.
PMID- 10198223
TI - Adamantyl globotriaosyl ceramide: a monovalent soluble mimic which inhibits
verotoxin binding to its glycolipid receptor.
AB - The globotriaosylceramide (Gb3) verotoxin (VT) interaction is one of several
examples of glycolipid receptors where the ceramide (or lipid) free
oligosaccharides fail to show the expected binding parameters. We present a
novel, yet simple strategy to synthesize monovalent, water soluble
glycosphingolipid mimics which retain receptor function. Replacing the fatty acid
chain with rigid, three dimensional hydrocarbon frames, such as adamantane, gives
a novel class of neohydrocarbon glycoconjugates. Such adamantyl conjugates
derived from Gb3 showed significantly enhanced solubility in water compared to
natural Gb3. Adamantyl-Gb3 showed a thousand fold enhanced inhibitory activity
(IC50 = 1 microM) for VT-Gb3 binding as compared to a lipid free Gb3
oligosaccharide derivative, alphaGal1-4betaGal1-4betaGlc1-O-CH2CH(CH2SO2C 4H9)2
(IC50 > 2 mM). This represents a new approach to the generation of antagonists of
glycolipid receptors.
PMID- 10198224
TI - Nitric oxide up-regulates the expression of intercellular adhesion molecule-1 on
cancer cells.
AB - Nitric oxide (NO) is an unstable free radical that functions as a cytotoxic agent
secreted by macrophages to kill cancer cells. Here we report the effect of NO on
the expression of intercellular adhesion molecule-1 (ICAM-1) on cancer cells. NO
donors such as SNP, SNAP and SIN-1 up-regulated the expression of ICAM-1 on NA
cells, a squamous cell carcinoma cell line. Northern blot analysis showed that
the induction of ICAM-1 might be due to transcriptional induction of ICAM-1 mRNA.
Up-regulation of ICAM-1 mRNA by NO donors was inhibited by carboxy-PTIO, a NO
scavenger. Although NF-kappaB activity was induced by NO donors, AP-1 was not
induced by them. Staurosporin, a protein kinase C (PKC) inhibitor, inhibited the
induction of ICAM-1 on NA cells by NO, whereas genistein, a protein tyrosine
kinase inhibitor, did not. These findings indicate that NO up-regulates ICAM-1
expression on cancer cells by a regulatory mechanism involving PKC and suggest
that NF-kappaB, but not AP-1, might be involved in induction of ICAM-1 by NO in
cancer cells.
PMID- 10198225
TI - Physical interaction between interleukin-12 receptor beta 2 subunit and Jak2
tyrosine kinase: Jak2 associates with cytoplasmic membrane-proximal region of
interleukin-12 receptor beta 2 via amino-terminus.
AB - IL-12 is a heterodimeric cytokine, composed of p40 and p35 subunits, that exerts
its biological effects by binding to specific cell surface receptors. Two human
IL-12 receptor proteins, designated IL-12R beta 1 and IL-12R beta 2, have been
previously identified. IL-12R beta 2 has box 1 motif, box 2 motif, and three
tyrosine residues in its cytoplasmic domain. In response to IL-12, Jak2 and Tyk2,
family members of Janus family protein tyrosine kinases, are phosphorylated in
PHA-activated T lymphocytes. The present study demonstrates that Jak2 binds to
the cytoplasmic membrane-proximal region of IL-12R beta 2, and box 2 motif and
tyrosine residues in the cytoplasmic domain were not required for binding. The
amino-terminus of Jak2 is necessary for association with IL-12R beta 2.
PMID- 10198226
TI - Chronic hyperammonemia in rats impairs activation of soluble guanylate cyclase in
neurons and in lymphocytes: a putative peripheral marker for neurological
alterations.
AB - Chronic hyperammonemia impairs the glutamate-nitric oxide-cGMP pathway in rat
brain in vivo. The aims of this work were to assess whether hyperammonemia
impairs modulation of soluble guanylate cyclase, and to look for a peripheral
marker for impairment of this pathway in brain. We activated the pathway at
different steps using glutamate, SNAP, or YC-1. In control neurons these
compounds increased cGMP by 7.4-, 9.7- and 7.2-fold, respectively. In ammonia
treated neurons formation of cGMP induced by glutamate, SNAP, and YC-1 was
reduced by 50%, 56%, and 52%, respectively, indicating that hyperammonemia
impairs activation of guanylate cyclase. This enzyme is also present in
lymphocytes. Activation of guanylate cyclase by SNAP or YC-1 was impaired in
lymphocytes from hyperammonemic rats. These results suggest that determination of
the activation of soluble guanylate cyclase in lymphocytes could serve as a
peripheral marker for impairment of the neuronal glutamate-nitric oxide-cGMP
pathway in brain.
PMID- 10198227
TI - PSC833, cyclosporin A, and dexniguldipine effects on cellular calcein retention
and inhibition of the multidrug resistance pump in human leukemic lymphoblasts.
AB - A convenient functional assay of the multidrug resistance (MDR) pump is useful
for the diagnosis of MDR-1 cancers and the quantitative determination of the
potency of inhibitors of the pump. Calcein-AM, a substrate of the MDR pump, was
used to determine the concentration of SDZ PSC833 needed to completely inhibit
the pump in CEM/VLB100 drug-resistant cells. The initial rates (in percent) for
calcein retention by these MDR-1 cells were used to calculate values for the
percent initial efflux of calcein-AM through the MDR pump in the presence of the
inhibitors PSC833, cyclosporinA, and dexniguldipine. The percent efflux values at
250 and 60 nM calcein-AM were used to calculate the required concentration of
each inhibitor to produce half-inhibition (I50) of initial efflux through the
pump. These results are consistent with a noncompetitive inhibition of the MDR
pump by each of the three inhibitors.
PMID- 10198228
TI - Threonine 188 is critical for interaction with NAD+ in human NAD+-dependent 15
hydroxyprostaglandin dehydrogenase.
AB - NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is the key enzyme
in the inactivation pathway of prostaglandins. It is a member of the short-chain
dehydrogenase family of enzymes. A relatively conserved threonine residue
corresponding to threonine 188 of 15-PGDH is proposed to be involved in the
interaction with the carboxamide group of NAD+. Site-directed mutagenesis was
used to examine the important role of this residue. Threonine 188 was changed to
alanine (T188A), serine (T188S) or tyrosine (T188Y) and the mutant proteins were
expressed in E. coli. Western blot analysis showed that the expression levels of
mutant proteins were similar to that of the wild type protein. Mutants T188A and
T188Y were found to be inactive. Mutant T188S still retained substantial activity
and the Km value for PGE2 was similar to the wild enzyme; however, the Km value
for NAD+ was increased over 100 fold. These results suggest that threonine 188 is
critical for interaction with NAD+ and contributes to the full catalytic activity
of 15-PGDH.
PMID- 10198229
TI - Crystal structure of mistletoe lectin I from Viscum album.
AB - The crystal structure of the ribosome-inactivating protein (RIP) mistletoe lectin
I (ML-I) from Viscum album has been solved by molecular replacement techniques.
The structure has been refined to a crystallographic R-factor of 24.5% using X
ray diffraction data to 2.8 A resolution. The heterodimeric 63-kDa protein
consists of a toxic A subunit which exhibits RNA-glycosidase activity and a
galactose-specific lectin B subunit. The overall protein fold is similar to that
of ricin from Ricinus communis; however, unlike ricin, ML-I is already medically
applied as a component of a commercially available misteltoe extract with
immunostimulating potency and for the treatment of human cancer. The three
dimensional structure reported here revealed structural details of this
pharmaceutically important protein. The comparison to the structure of ricin
gives more insights into the functional mechanism of this protein, provides
structural details for further protein engineering studies, and may lead to the
development of more effective therapeutic RIPs.
PMID- 10198230
TI - Colocalization of leptin receptor (OB-R) mRNA and placental lactogen-II in rat
trophoblast cells: gestational profile of OB-R mRNA expression in placentae.
AB - The present study was designed to clarify the cellular localization and
expression of leptin receptor(s) [OB-R(s)] mRNA including its splice variants and
their correlation with the cells which secrete placental hormone, placental
lactogen-II (PL-II), in rat placentae. By in situ hybridization analysis,
hybridization signals for OB-Rb and the common extracellular domain of OB-R were
first detectable in some cells of the labyrinth zone of the placentae on day 14
of pregnancy and then a lot of cells dispersed in the entire area of the
labyrinth zone expressed OB-Rb during the latter half of pregnancy. However, no
expression was observed in the decidua and the junctional zone of the placentae
during pregnancy. Double staining study revealed that signals for OB-R expressing
trophoblast cells showed PL-II immunoreactivity in the labyrinth zone of the
placentae. In Northern blot analysis, two bands (2.8 kb and 5.1 kb) of OB-R mRNA
expression were observed in the placentae from day 17 to 21 of pregnancy and the
expression of both increased markedly up to day 21 of pregnancy. RT-PCR analysis
revealed that OB-Rb, OB-Ra, and OB-Re are expressed in the placentae on days 19
and 21 of pregnancy. These results suggest that the OB-R may have a physiological
significance in the placental function during the latter half of pregnancy.
PMID- 10198231
TI - Identification of the factors affecting the rate of deactivation of hypochlorous
acid by melatonin.
AB - It has been found that melatonin reacts rapidly with hypochlorous acid in
phosphate-buffered, ethanol-water solutions to produce 2-hydroxymelatonin. The
rate law, d[2 - HOMel]/dt - kHOCl[Mel][HOCl] - kOCl-[Mel][OCl-], was obtained. At
37 degrees C and at a water concentration of 23.5 M, kOCl- = 6.0 x 10(2) L. mol
1. s-1, and kHOCl was found to be a function of the water concentration, kHOCl =
11 +/- 3 L3. mol-3. s-1. [H2O]2, indicating that the availability of water at the
site of the reaction plays a significant role. The part that the structural
components of melatonin play in determining the reaction pathway was examined by
comparing the rate of deactivation of HOCl by melatonin to that of the model
compounds indole, 5-methoxyindole, and 3-methylindole. The relative reactivity is
explained in terms of steric and electronic effects, and it was found that the
presence of the substituent at the 3-position influences the nature of the
oxidation product. Melatonin and 3-methylindole yielded hydroxylated products,
whereas indole and 5-methoxyindole produce chlorinated products.
PMID- 10198232
TI - Glucose protection from MPP+-induced apoptosis depends on mitochondrial membrane
potential and ATP synthase.
AB - MPP+ inhibits mitochondrial complex I and alpha-ketoglutarate dehydrogenase
causing necrosis or apoptosis of catecholaminergic neurons. Low glucose levels or
glycolytic blockade has been shown to potentiate MPP+ toxicity. We found that
MPP+ caused concentration-dependent apoptosis of neuronally differentiated PC12
cells and that glucose, but not pyruvate, supplementation reduced apoptosis.
Oligomycin concentrations sufficient to inhibit ATP synthase blocked the
decreased apoptosis afforded by glucose supplementation. Laser-scanning confocal
microscope imaging of chloromethyl-tetramethylrosamine methyl ester fluorescence
to estimate DeltaPsiM showed that MPP+ and atractyloside reduced DeltaPsiM, while
cyclosporin A (CSA) and glucose supplementation reversed decreases in DeltaPsiM
caused by MPP+. Oligomycin blocked the effect of glucose supplementation on
DeltaPsiM. These findings show that (i) MPP+-induced and atractyloside-induced
apoptosis are associated with reduced DeltaPsiM; (ii) CSA maintains DeltaPsiM and
reduces MPP+-induced apoptosis; and (iii) glucose supplementation maintains
DeltaPsiM, likely by glycolytic ATP-dependent proton pumping at ATP synthase and
reduces MPP+-induced apoptosis.
PMID- 10198233
TI - Molecular design of conjugated tumor necrosis factor-alpha: synthesis and
characteristics of polyvinyl pyrrolidone modified tumor necrosis factor-alpha.
AB - We conjugated tumor necrosis factor-alpha (TNF-alpha) with the synthetic
polymeric modifier polyvinyl pyrrolidone (PVP) to facilitate its clinical use for
anti-tumor therapy. TNF-alpha was chemically conjugated with the terminal
carboxyl-bearing PVP at one end of its main chain, which was radically
polymerized via the formation of an amide bond between the lysine amino groups of
TNF-alpha and carboxyl group of PVP. In vitro specific bioactivity of PVP
conjugated TNF-alpha (PVP-TNF-alpha) relative to that of native TNF-alpha
gradually decreased with increases in the degree of PVP attachment. In contrast,
PVP-TNF-alpha in which 40% of TNF-alpha lysine residues were coupled with PVP
(MPVP-TNF-alpha) exhibited the highest anti-tumor activity among the conjugated
derivatives examined. MPVP-TNF-alpha had more than 200-fold higher anti-tumor
efficacy than native TNF-alpha, and the anti-tumor activity of MPVP- TNF-alpha
was more than 5-fold stronger than that MPEG- TNF-alpha which had the highest
anti-tumor activity among PEG-conjugated TNF-alphas examined. Additionally, a
high dose of native TNF-alpha induced toxic side-effects such as body weight
reduction, piloerection and tissue inflammation, while no side effects were
observed following i.v. administration of MPVP-TNF-alpha. The plasma half-life of
MPVP-TNF-alpha (360 min) was about 80 and 3-fold longer than those of native TNF
alpha (4.6 min) and MPEG-TNF-alpha (122 min), respectively. These results
suggested that PVP is a useful polymeric modifier for increasing the anti-tumor
activity of PVP.
PMID- 10198234
TI - Expression of TRAIL and its receptors in human brain tumors.
AB - Recently, TRAIL has been demonstrated to selectively induce apoptosis in
transformed cell lines, and subsequently four receptors (TRAIL-R1-TRAIL-R4) have
been identified. The ability to transduce death signals is restricted to TRAIL
R1/TRAIL-R2. In contrast, TRAIL-R3/TRAIL-R4 are unable to activate apoptotic
pathways and have therefore been suggested to act as "decoys" protecting normal
tissues from cell death. However, the biological role of the TRAIL system remains
incompletely understood. We analyzed the expression of TRAIL and its receptors in
a panel of human brain tumors (n = 34) and in four glioma cell lines in
comparison to normal brain tissue. Constant co-expression of TRAIL and of
receptors TRAIL-R1, TRAIL-R2, and TRAIL-R3 in different tumor entities as well as
in normal brain indicates that additional mechanisms might modulate the
previously proposed "decoy" model. Furthermore, in contrast to previous reports,
we demonstrate TRAIL and TRAIL-R2 to be present on a transcriptional level in
normal brain tissue. Exceptional expression of TRAIL-R4 transcripts does not
suggest a significant regulatory role of this receptor in the human brain and its
tumors.
PMID- 10198235
TI - 2-deoxy-d-ribose-induced apoptosis in HL-60 cells is associated with the cell
cycle progression by spermidine.
AB - The presence of polyamines is required for the apoptotic program triggered by 2
deoxy-D-ribose (dRib) in HL-60 cells, but their oxidative metabolites does not
appear to be involved in the oxidative stress caused by the sugar. The present
study points to a relationship between spermidine-induced G1 to S phase
transition and the onset of dRib-induced apoptosis. Conversely, the G1 block
induced by alpha-difluoromethylornithine (DFMO) is associated with a protective
effect against dRib-induced cell suicide. Replenishment of the intracellular
spermidine pool by exogenous putrescine and spermidine induces cell cycle
progression and restores apoptotic levels. The present data indicate that the
induction of cell cycle progression by spermidine is a condition facilitating the
activation of the apoptotic process by dRib.
PMID- 10198236
TI - Origin of guanine nucleotides in isolated heart mitochondria.
AB - Presence of guanine nucleotide within the matrix of mitochondria is uncontested;
the mechanism by which GTP takes up residence in the matrix is unknown. In this
report, we demonstrate for the first time that direct transport of guanine
nucleotide across the inner membrane of heart mitochondria is possible. Transport
of guanine nucleotides from the medium to the matrix was suggested by inhibition
of translation in isolated rat heart mitochondria when GTP-gamma-S was added to
the medium. This result suggested that GTP was one source of matrix GTP. Other
sources were investigated by measuring matrix uptake and conversion to GTP of
several purines, purine nucleosides, and purine nucleotides. Results demonstrated
that [14C]-guanine and [3H]-guanosine were not taken up by isolated mitochondria
and were not converted to any other compound. While [14C]-ATP and [3H]-AMP were
taken up readily into the matrix, radioactivity was never associated with a
guanine compound. [3H]-IMP was not taken up into the matrix and was never
converted to another compound. Our data showed that label added as [3H]-GTP, [3H]
GDP, or [3H]-GMP was readily taken up and concentrated in the matrix of isolated
mitochondria.
PMID- 10198237
TI - Protein 7B2 is essential for the targeting and activation of PC2 into the
regulated secretory pathway of rMTC 6-23 cells.
AB - Among the prohormone convertases, PC2 is unique in that it specifically binds to
the neuroendocrine-specific protein 7B2 in the endoplasmic reticulum (ER) and is
activated late in the regulated secretory pathway of neuroendocrine cells.
Several roles, sometimes contradictory, have been suggested for 7B2 with regard
to PC2 cellular fate. Thus, 7B2 was proposed to act as a PC2 chaperone in the ER,
or to facilitate 7B2 transport from the ER to the trans-Golgi network and to be
necessary for proPC2 activation, or to inhibit PC2 enzymatic activity until the
latter reaches the secretory granules. To gain insight into the function of 7B2,
we sought to block its expression in PC2-expressing endocrine cells using
antisense strategies. We have previously shown that the endocrine rMTC 6-23 cell
line expresses PC2 and that the enzyme is responsible for the processing of pro
neurotensin/neuromedin N (proNT/NN). Here, we show that rMTC 6-23 cells express
7B2 and that the protein was coordinately induced with PC2 and proNT/NN by
dexamethasone. Stable transfection of rMTC 6-23 cells with 7B2 antisense cDNA led
to a marked reduction (>90%) in 7B2 levels. ProPC2 was expressed to normal levels
and cleaved to yield a PC2 form that was constitutively released, was not stored
within secretory granules and was unable to process proNT/NN. We conclude that
7B2 is essential for the sorting and activation of PC2 into the regulated
secretory pathway of endocrine cells.
PMID- 10198238
TI - Characterization of MARCKS (Myristoylated alanine-rich C kinase substrate)
identified by a monoclonal antibody generated against chick embryo neural retina.
AB - To identify molecular markers of cell differentiation in developing nervous
tissue, monoclonal antibodies against chick embryo neural retina were made. One
of them, 3C3mAb, recognized a developmentally regulated antigen present in
several organs of the CNS. Data from MALDI-TOF mass spectrometry and peptide
sequencing of the immuno-affinity purified protein indicated identity of the
antigen with MARCKS. The immunoreactive material was always found as a unique
polypeptide (Mr 71 kDa) in SDS-PAGE, however isoelectrofocusing revealed the
existence of several bands (pI ranging from 4.0 to 4.5). Interestingly some
retinal cell types, as photoreceptors, exhibited an extremely significant
decrease in the intensity of the immunoreactive material during the final phases
of terminal differentiation while others, as some retinal neurons, maintained the
immunoreactivity when fully differentiated. Taken together these results indicate
that MARCKS, a protein susceptible of several posttranslational modifications as
myristoylation and phosphorylation at variable extent, may act differently in
neural retina cell types.
PMID- 10198239
TI - Production of prostanoids and nitric oxide by infarcted heart in situ and the
effect of aspirin.
AB - The production of prostacyclin (PGI2) and thromboxane A2 (TXA2) in infarcted and
noninfarcted portions of the rabbit heart was studied prior to and following
administration of acetylsalicylic acid (aspirin). Aspirin was administered
intravenously (iv) as water-soluble Aspisol, d-lysinmono (acetylsalicylate)
(Bayer, Leverkusen, Germany) into an ear vein. A branch of the left circumflex
coronary artery was ligated. The animals were divided into three groups. The
first group received 150 mg/kg/day of aspirin (75 mg/kg of aspirin every 12 h, n
= 10). The first administration of aspirin was 1 h after ligation of the coronary
artery and the last injection was 1 h before euthanasia. The second group
received 5 mg/kg/day of aspirin (every 24 h, n = 10). A separate group of rabbits
not receiving aspirin served as controls (n = 12). Two days following onset of
ischemia, inducible form of nitric oxide synthase (iNOS) was measured in heart
muscle and the oxidation products of nitric oxide (nitrite, NO-2 plus nitrate, NO
3: their sum referred to as NOx) were determined in arterial and coronary venous
blood. Concentrations of both PGI2 and TXA2 were elevated in the infarcted
portions of the heart compared to the noninfarcted regions. Formation of
prostanoids was accompanied by increased activation of iNOS. Both doses of
aspirin diminished the concentrations of PGI2 and TXA2 in infarcted heart muscle;
in contrast, small doses of aspirin failed to influence myocardial iNOS activity.
Apparently small doses of aspirin changed the relationship of iNOS to
cyclooxygenase (COX). Coronary arterial-venous difference of NOx and myocardial
iNOS activity showed parallel increases. Diminution of prostacyclin by aspirin
can damage gastric mucosa and interfere with vasodilatation. Since NO counters
these deficiencies, a combination of aspirin with a nitric oxide donor may be
advantageous.
PMID- 10198240
TI - Tissue inhibitor of metalloproteinases-1 (TIMP-1) binds to the cell surface and
translocates to the nucleus of human MCF-7 breast carcinoma cells.
AB - To study cellular and subcellular localization of TIMP-1, we constructed a cDNA
which would express a chimeric protein, TIMP-1-EGFP, having the enhanced green
fluorescent protein of the jelly fish Aequorea victoria fused to the carboxyl
terminus of TIMP-1. Chinese Hamster Ovary (CHO) cells were stably transfected
with the TIMP-1-EGFP expressing plasmid. The secreted chimera was processed
through the endoplasmic reticulum and Golgi, as was shown by fluorescent confocal
microscopy after incubations at temperatures which block processing at the
intermediate compartment and the trans-Golgi network. In a co-culture system,
secreted TIMP-1-EGFP could be visualized binding to the surface of MCF-7 breast
carcinoma cells but not non-neoplastic HBL-100 breast epithelial cells. TIMP-1
EGFP localized to the nucleus of MCF-7 cells after 72 hrs in co-culture. These
findings suggest that TIMP-1 may preferentially bind to and be taken up by
malignant breast epithelial cells and that TIMP-1 may play a yet unidentified
role in nuclear functions.
PMID- 10198241
TI - Comparison of three classes of snake neurotoxins by homology modeling and
computer simulation graphics.
AB - We present a systematic structure comparison of three major classes of
postsynaptic snake toxins, which include short and long chain alpha-type
neurotoxins plus one angusticeps-type toxin of black mamba snake family. Two
novel alpha-type neurotoxins isolated from Taiwan cobra (Naja naja atra)
possessing distinct primary sequences and different postsynaptic neurotoxicities
were taken as exemplars for short and long chain neurotoxins and compared with
the major lethal short-chain neurotoxin in the same venom, i.e., cobrotoxin,
based on the derived three-dimensional structure of this toxin in solution by NMR
spectroscopy. A structure comparison among these two alpha-neurotoxins and
angusticeps-type toxin (denoted as FS2) was carried out by the secondary
structure prediction together with computer homology-modeling based on multiple
sequence alignment of their primary sequences and established NMR structures of
cobrotoxin and FS2. It is of interest to find that upon pairwise superpositions
of these modeled three-dimensional polypeptide chains, distinct differences in
the overall peptide flexibility and interior microenvironment between these
toxins can be detected along the three constituting polypeptide loops, which may
reflect some intrinsic differences in the surface hydrophobicity of several
hydrophobic peptide segments present on the surface loops of these toxin
molecules as revealed by hydropathy profiles. Construction of a phylogenetic tree
for these structurally related and functionally distinct toxins corroborates that
all long and short toxins present in diverse snake families are evolutionarily
related to each other, supposedly derived from an ancestral polypeptide by gene
duplication and subsequent mutational substitutions leading to divergence of
multiple three-loop toxin peptides.
PMID- 10198242
TI - Mouse thyroid primary culture.
AB - Technological advances have drastically decreased the number of cells required to
analyze expression of the genes and functions of the encoded proteins, making
even a small organ like a mouse thyroid amenable to study in vitro. We have
established primary cultures of mouse thyroids that showed, for up to 14 days
after seeding, strong cytoplasmic staining for thyroglobulin. The staining then
gradually decreased and was present in only 5-10% of thyrocytes at day 28.
Furthermore, cultured thyrocytes expressed the thyroperoxidase and thyrotropin
receptor genes, and, although at lower levels, the sodium-iodide symporter gene.
Finally, cultured thyrocytes could be transiently transfected by lipofection,
using FuGENE 6. Thus, we report that it is possible to cultivate functional
primary mouse thyrocytes that can be used for a variety of biological studies.
This system is appealing because it permits the use of the ever-increasing number
of transgenic, knock-out and knock-in mouse strains in studying thyroid
pathophysiology.
PMID- 10198243
TI - Epithelial-cell-specific transcriptional regulation of human
Galbeta1,3GalNAc/Galbeta1,4GlcNAc alpha2,3-sialyltransferase (hST3Gal IV) gene.
AB - The mRNA expression of the sialyltransferase genes is regulated in a cell type
specific manner. We show here the epithelium cell-specific transcriptional
regulation of the human Galbeta1, 3GalNAc/Galbeta1, 4 GlcNAc alpha2,3
sialyltransferase gene (hST3Gal IV). Using a luciferase assay, we identified a
functional DNA portion within hST3Gal IV genomic DNA that confers an epithelial
cell line specific enhancer, located in nucleotide number (nt) -520 to -420
within the B3 promoter. This element contains two sequences similar to AP2
recognition motifs. Co-transfection with an AP2 expression vector stimulated the
enhancer activity of nt -520 to -420 element eight-fold compared with that using
parental vector. Site-directed mutagenesis of AP2 sites showed that two AP2
motifs are essential for enhancer activity in HeLa cells. These results suggest
that AP2 plays a critical role in the epithelium-cell specific transcriptional
regulation of the hST3Gal IV gene.
PMID- 10198244
TI - Nonspecific inhibition of myogenic tone by PD98059, a MEK1 inhibitor, in rat
middle cerebral arteries.
AB - Activation of MAP kinase kinase, also called ERK kinase (MEK), may lead to
desinhibition of thin filament regulatory proteins and we therefore investigated
the acute effects of the potent MEK inhibitor, PD98059 on the contractile
properties of pressurized rat middle cerebral arteries. Cerebral arteries
(diameter 100-150 microm) were mounted on a pressure myograph and PD98059 (10
microM, 40 microM) significantly inhibited (15% and 64%) myogenic tone (P <
0.001). At these concentrations, PD98059 also significantly reduced the
vasopressin (0.1 microM)- and KCl (60 mM)-induced tone. Cumulative addition of
exogenous Ca2+ (0.4-1.6 mM) increased myogenic tone to approximately 50% of
constriction at 80 mmHg. This effect was inhibited by PD98059 (P < 0.001). These
results demonstrate that pressure-induced myogenic tone is inhibited by PD98059
at the concentrations that have been reported to be selective for inhibition of
MEK and the MAP kinase cascade. However, our results also demonstrate that
PD98059 may have nonspecific effects on voltage-sensitive Ca2+ entry in vascular
smooth muscle.
PMID- 10198245
TI - Involvement of tyrosine kinases on cyclooxygenase expression and prostaglandin E2
production in human gingival fibroblasts stimulated with interleukin-1beta and
epidermal growth factor.
AB - The purpose of the present study was to investigate the involvement of
cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), and tyrosine kinase on
prostaglandin E2 (PGE2) production in human gingival fibroblasts stimulated by
interleukin-1beta (IL-1beta) and/or epidermal growth factor (EGF). The cytokine
IL-1beta and to a lesser extent EGF, enhanced COX-2 mRNA levels in gingival
fibroblasts. Simultaneous treatment with EGF and IL-1beta resulted in enhanced
COX-2 mRNA levels accompanied by a synergistic stimulation of PGE2 biosynthesis
compared to the cells treated with IL-1beta or EGF alone. Neither IL-1beta EGF
nor the combination of IL-1beta and EGF enhanced COX-1 mRNA levels in gingival
fibroblasts. The tyrosine kinase inhibitors, Herbimycin A and PD 153035
hydrochloride, reduced COX-2 mRNA levels as well as PGE2 production induced by IL
1beta or the combination of IL-1beta and EGF whereas COX-1 mRNA levels were not
affected. Furthermore, the COX-2 specific inhibitor, NS-398, abolished the PGE2
production induced by IL-1beta, EGF, or the combination. These results indicate
that the synergy between IL-1beta and EGF on PGE2 production is due to an
enhanced gene expression of COX-2 and that tyrosine kinase(s) are involved in the
signal transduction of COX-2 in gingival fibroblasts.
PMID- 10198246
TI - Isolation and characterization of a genomic region upstream from the ovine Na+/d
glucose cotransporter (SGLT1) cDNA.
AB - d-Glucose and non-metabolisable analogues of D-glucose regulate the expression of
intestinal SGLT1 at both transcriptional and post-transcriptional levels. In
order to investigate the molecular mechanisms involved in the transcriptional
regulation of the ovine intestinal SGLT1 gene, we have isolated an upstream
element of about 1 kb in size. This DNA fragment contains a TATA box motif, 48 bp
upstream of the transcriptional start site and includes transcription factor
binding sites for HNF-1 and AP-2. We have shown that the ovine SGLT1 promoter
fragment can drive the transcription of a reporter gene when transfected into the
epithelial cell lines STC-1 and LLC-PK1, which endogenously express SGLT1.
Deletion analyses of the promoter indicate that -66/+21 bp proximal sequence
directs the highest level of reporter gene activity. There are one and possibly
two sites of transcriptional suppression.
PMID- 10198247
TI - Identification of a novel cis-acting positive element responsible for the cell
specific expression of the NK-1 homeobox gene.
AB - The Drosophila NK-1 homeobox gene belongs to the NK-1 class that includes a large
number of vertebrate homeobox genes and is shown to be expressed in specific
muscle founder cells and a subset of neuronal cells in the ventral nerve cord
during embryogenesis. To determine the cis-acting regulatory elements controlling
the cell-specific expression of NK-1, we measured transiently expressed
chloramphencol acetyl transferase (CAT) reporter gene activities from transfected
C2C12 myoblasts and NG108-15 neuroblastoma cells using various CAT constructs
containing different 5' upstream regions of NK-1. From the initial analysis of
3.9 kb of the 5' upstream region, we have found that the regions from -1865 to
476 and from -476 to +100 contained strong negative and positive regulatory
elements, respectively. Within the positive cis-acting region an 86-bp DNA
fragment (from -435 to -350) was sufficient to activate the reporter gene in
C2C12 cells, whereas additional regions (from -157 to -28 and from -510 to -425)
were required for optimal activity in NG108-15 cells. Gel shift and DNaseI
footprinting assays have defined a plausible binding site for C/EBP, 5'-TTTCGCAAG
3' (-424 to -416), and a novel binding site for unknown factors, 5'
AATTACTCACATCC-3' (-370 to -357). Further mutation analysis has revealed that the
novel binding sequence for unknown factors is necessary and sufficient for
transcriptional activity for reporter gene expression in C2C12 myoblast cells in
an orientation-independent manner.
PMID- 10198248
TI - Sorting of a constitutive secretory protein to the regulated secretory pathway of
exocrine cells.
AB - Exocrine cells secrete granule proteins by regulated or constitutive-like
secretory pathways. It is thought that all secretory proteins can enter immature
secretory granules in exocrine cells. To test this hypothesis, we expressed the
constitutive secretory protein secreted alkaline phosphatase (SEAP) in the
exocrine cell line AR42J and compared its secretion to that of amylase, an
endogenous regulated secretory protein. Secretion of SEAP and amylase were
stimulated about 1.5-fold by substance P and 2-fold by barium chloride. In
dexamethasone-treated cells, SEAP and amylase secretion were stimulated about 1.8
fold by substance P, 5-fold by barium chloride, and 4-fold by cholecystokinin-8.
Cycloheximide reduced basal secretion of SEAP and amylase by 50%, increasing
cholecystokinin-stimulated secretion to about 10-fold. Sodium butyrate induced
expression of SEAP 2-fold but had no effect on stimulated secretion. These
results suggest that SEAP is stored in secretory granules in AR42J cells.
PMID- 10198249
TI - Ca2+-activated K channel of the BK-type in the inner mitochondrial membrane of a
human glioma cell line.
AB - A single channel current was recorded from mitoplasts (i.e., inner mitochondrial
membrane) of the human glioma cell line LN229 using patch-clamp techniques in the
mitoplast-attached mode. We frequently found a 295 +/- 18 pS channel that showed
a straight i-E relation in the range +/-60 mV in 150 mM KCl solutions on either
side of the mitoplast. If KCl in the bath was exchanged against NaCl, outward
currents were undetectable, indicating potassium selectivity. Channel activity
determined as open probability increased with increasing Ca2+ concentrations
(EC50 = 0.9 microM at 60 mV). Open probability was voltage dependent. An e-fold
increase of time spent in the open state was induced by a depolarization of 10.5
mV. Open probability was decreased by charybdotoxin concentration and voltage
dependently (EC50 = 1.4 nM). In conclusion, we show for the first time that the
inner mitochondrial membrane in human glioma cells contains a calcium-dependent K
channel of the BK-type.
PMID- 10198250
TI - Oxidative DNA damage by a metabolite of carcinogenic and reproductive toxic
nitrobenzene in the presence of NADH and Cu(II).
AB - The mechanism of DNA damage induced by metabolites of nitrobenzene was
investigated in relation to the carcinogenicity and reproductive toxicity of
nitrobenzene. Nitrosobenzene, a nitrobenzene metabolite, induced NADH plus Cu(II)
mediated DNA cleavage frequently at thymine and cytosine residues. Catalase and
bathocuproine inhibited the DNA damage, suggesting the involvement of H2O2 and
Cu(I). Typical free hydroxyl radical scavengers showed no inhibitory effects on
DNA damage. Nitrosobenzene caused the formation of 8-oxo-7, 8-dihydro-2'
deoxyguanosine in calf thymus DNA in the presence of NADH and Cu(II). ESR
spectroscopic study has confirmed that nitrosobenzene is reduced by NADH to the
phenylhydronitroxide radical even in the absence of Cu(II). These results suggest
that nitrosobenzene can be reduced non-enzymatically by NADH, and the redox cycle
reaction resulted in oxidative DNA damage due to the copper-oxygen complex,
derived from the reaction of Cu(I) with H2O2.
PMID- 10198251
TI - The yeast Npi1/Rsp5 ubiquitin ligase lacking its N-terminal C2 domain is
competent for ubiquitination but not for subsequent endocytosis of the gap1
permease.
AB - The yeast ubiquitin ligase Npi1/Rsp5 and its mammalian homologue Nedd4 are
involved in ubiquitination of various cell surface proteins, these being
subsequently internalized by endocytosis and degraded in the vacuole/lysosome.
Both enzymes consist of an N-terminal C2 domain, three to four successive WW(P)
domains, and a C-terminal catalytic domain (HECT) containing a highly conserved
cysteine residue involved in ubiquitin thioester formation. In this study, we
show that the conserved cysteine of the HECT domain is required for yeast cell
viability and for ubiquitination and subsequent endocytosis of the Gap1 permease.
In contrast, the C2 domain of Npi1/Rsp5 is not essential to cell viability. Its
deletion impairs internalization of Gap1, without detectably affecting
ubiquitination of the permease. This suggests that Npi1/Rsp5 participates, via
its C2 domain, in endocytosis of ubiquitinated permeases.
PMID- 10198252
TI - Identification of the dehydroascorbic acid reductase and thioltransferase
(Glutaredoxin) activities of bovine erythrocyte glutathione peroxidase.
AB - Bovine erythrocyte glutathione (GSH) peroxidase (GPX, EC 1.11.1.9) was examined
for GSH-dependent dehydroascorbate (DHA) reductase (EC 1.8.5.1) and
thioltransferase (EC 1.8.4.1) activities. Using the direct assay method for GSH
dependent DHA reductase activity, GPX had a kcat (app) of 140 +/- 9 min-1 and
specificity constants (kcat/Km(app)) of 5.74 +/- 0.78 x 10(2) M-1s-1 for DHA and
1.18 +/- 0.17 x 10(3) M-1s-1 for GSH based on the monomer Mr of 22,612. Using the
coupled assay method for thioltransferase activity, GPX had a kcat (app) of 186
+/- 9 min-1 and specificity constants (app) of 1. 49 +/- 0.14 x 10(3) M-1s-1 for
S-sulfocysteine and 1.51 +/- 0.18 x 10(3) M-1s-1 for GSH based on the GPX monomer
molecular weight. GPX has a higher specificity constant for S-sulfocysteine than
DHA, and both assay systems gave nearly identical specificity constants for GSH.
The DHA reductase and thioltransferase activities of GPX adds to the repertoire
of functions of this enzyme as an important protector against cellular oxidative
stress.
PMID- 10198253
TI - Hypochlorous acid-induced DNA base modification: potentiation by nitrite:
biomarkers of DNA damage by reactive oxygen species.
AB - Chronic inflammation results in increased nitric oxide formation and nitrite (NO
2) accumulation. Activated phagocytes release myeloperoxidase generating the
cytotoxic agent hypochlorous acid (HOCl). Reaction of HOCl with NO-2 results in
the formation of nitryl chloride (NO2Cl), a potent oxidising, nitrating and
chlorinating species. Exposure of DNA to NO-2 alone (up to 250 microM) at pH 7.4
did not induce oxidative DNA base damage. However, incubation of DNA with NO-2 in
the presence of HOCl led to increases in thymine glycol, 5-hydroxyhydantoin, 8
hydroxyadenine and 5-chlorouracil to levels higher than those achieved by HOCl
alone. No significant increases in 8-hydroxyguanine, xanthine, hypoxanthine, 2
hydroxyadenine, FAPy guanine, FAPy adenine and 8-chloroadenine were observed.
HOCl-induced depletion of FAPy guanine and 8-hydroxyguanine was reduced in the
presence of NO-2. Modification of DNA by HOCl/NO-2 (presumably generating NO2Cl)
produces a pattern of DNA base damage products in isolated DNA that is similar to
the pattern produced by HOCl but not other reactive species.
PMID- 10198254
TI - Molecular cloning, expression analysis, and chromosomal localization of human
syntaxin 8 (STX8).
AB - We report the cloning of a cDNA encoding human syntaxin 8 (STX8), using the
regulator (R) domain of the cystic fibrosis transmembrane conductance regulator
(CFTR) as a bait to screen a human fetal lung cDNA library by the yeast two
hybrid system. This gene was found broadly transcribed and its mRNA size is about
1.3 kb. The STX8 gene maps to chromosomal band 17p12 and it encodes a 236-amino
acid protein. Syntaxin 8 contains in its C-terminal half a coiled-coil domain
found highly conserved in the t-SNARE (SNAP receptor on target membrane)
superfamily of proteins, which are involved in vesicular trafficking and docking.
In syntaxin 8, a C-terminal hydrophobic domain may constitute a transmembrane
anchor. It was recently shown that CFTR-mediated chloride currents can be
regulated by syntaxin 1A, a t-SNARE family member, through direct protein-protein
interaction. This raises the possibility that syntaxin 8 may also be involved in
such regulations.
PMID- 10198255
TI - A novel apolipoprotein A-1 variant, Arg173Pro, associated with cardiac and
cutaneous amyloidosis.
AB - An American kindred was found to have hereditary amyloidosis with cutaneous and
cardiac involvement. Characterization of fibrils isolated from skin identified
the amyloid protein as the N-terminal 90 to 100 residues of apolipoprotein A-1.
Sequence of the apolipoprotein A-1 gene was normal except for a G/C transversion
at position 1638 which predicts an Arg to Pro substitution at residue 173. This
mutation, unlike previously described amyloidogenic mutations is not in the N
terminal fragment which is incorporated into the fibril. The mutation is at the
same residue as in apolipoprotein A-1 Milano (Arg173Cys) which does not result in
amyloid formation. Decreased plasma HDL cholesterol levels in carriers of the
Arg173Pro mutation suggest an increased rate of catabolism as has been shown for
the amyloidogenic Gly26Arg mutation. This suggests that altered metabolism caused
by the mutation may be a significant factor in apolipoprotein A-1
fibrillogenesis.
PMID- 10198256
TI - Phosphorylation of human MAD1 by the BUB1 kinase in vitro.
AB - The BUB/MAD signaling pathway monitors attachment of chromosomes to spindle poles
in mitotic cells. Mutations of the human BUB1 locus were identified in cancer
cells exhibiting an unstable chromosomal complement. We report that the human
BUB3 gene maps to a site on chromosome 10 subject to frequent modification in
cancers. Thus, defects in BUB/MAD signaling may contribute to genetic instability
and to cancer progression. In vitro, BUB1 and BUB3 proteins form a complex of
monomers of each protein. These proteins interact with the human MAD1 gene
product, a target of the HTLV-1 tax oncogene. This multiprotein complex exhibits
a kinase activity with a requirement for lysine 821 in the BUB1 kinase motif,
resulting in BUB1 autophosphorylation and phosphorylation of associated MAD1.
PMID- 10198257
TI - Optimization of treatment conditions for studying the anticancer effects of
retinoids using pancreatic adenocarcinoma as a model.
AB - Retinoids are natural differentiation-inducing compounds that are promising as
anticancer agents. Cancer cell lines are valuable in the investigation of the
potential of retinoids for the treatment of specific cancers. However, using
different treatment conditions but the same cell lines, investigators have
produced markedly contradictory results for the effectiveness of retinoids. The
present study examined different factors in the treatment conditions that may
have masked or interfered with the effects of retinoids and, thereby, resulted in
this conflict. Our studies revealed that the effects of retinoids on cancer cell
proliferation were influenced by serum, the choice of vehicle (DMSO vs ethanol)
and its concentration, phenol red, the degree of cellular confluence, and the
method of assessing proliferation (cell number or [3H]thymidine uptake vs the MTT
assay). Optimized conditions were the use of serum-free, ethanol-free, and phenol
red-free media, investigating cells in the log phase of growth, using =0.01%
DMSO as the vehicle, and monitoring proliferation by cell number or [3H]thymidine
incorporation into DNA measured after TCA precipitation. Using these conditions,
retinoids were found to exhibit potent antiproliferative effects in pancreatic
cancer cells with a variety of degrees of differentiation, even in cell lines
previously documented as being retinoid resistant. Retinoids also induced
morphological changes and cellular death that may indicate terminal
differentiation and apoptosis.
PMID- 10198258
TI - Lack of reciprocal genomic imprinting of sense and antisense RNA of mouse insulin
like growth factor II receptor in the central nervous system.
AB - Two models have been proposed to account for the molecular mechanism underlying
genomic imprinting of the insulin-like growth factor II receptor gene (Igf2r):
expression-competition and promoter DNA methylation. To examine which model best
explains the regulation of Igf2r imprinting, we examined the allelic expression
of endogenous Igf2r sense and antisense RNAs in mice. In peripheral tissues,
Igf2r sense and antisense RNAs show a reciprocal pattern of imprinting and DNA
methylation between the two parental alleles: the sense RNA is monoallelically
expressed only from the maternal promoter which is unmethylated in region 1, and
the antisense RNA is derived solely from the paternal promoter which is
unmethylated in region 2. The paternal promoter of sense Igf2r and the maternal
promoter of antisense Igf2r are hypermethylated and are transcriptionally
suppressed. In CNS, the genomic imprinting of Igf2r sense and antisense RNAs is
uncoupled: both parental promoters of Igf2r gene coding for sense RNA are
unmethylated and are biallelically used for transcription. In contrast, antisense
RNA of Igf2r is derived only from the paternal allele that is unmethylated in
region 2, while the methylated maternal allele is silent. Uncoupling of genomic
imprinting of Igf2r sense and antisense RNAs in CNS correlates with DNA
methylation of the appropriate promoter region, thus favoring the model of DNA
methylation over that of antisense as the chief regulator of Igf2r genomic
imprinting.
PMID- 10198259
TI - Interleukin-6 induces G1 arrest through induction of p27(Kip1), a cyclin
dependent kinase inhibitor, and neuron-like morphology in LNCaP prostate tumor
cells.
AB - Prostate carcinoma cells express high levels of interleukin-6 (IL-6) and IL-6
receptor. In this study, we examined the effect of IL-6 on LNCaP human prostate
carcinoma cells. IL-6 induces G1 growth arrest of LNCaP. Following IL-6 treatment
of LNCaP, Western blot analysis showed that the protein levels of cyclin
dependent kinase-2 (CDK2), CDK4, and CDK6 were decreased, while accumulation of
CDK inhibitor p27(Kip1) was rapidly and markedly induced. In vitro kinase assays
revealed that the CDK-associated histone H1 and CDK4- and CDK6-associated pRb
kinase activities were significantly inhibited in IL-6-treated LNCaP. Further, a
significant amount of p27(Kip1) was co-precipitated with CDK2, CDK4 and CDK6, as
detected in immunoprecipitation experiments. Thus, IL-6-induced G1 arrest appears
to be due to the accumulation of p27(Kip1). In addition, IL-6-treated LNCaP cells
induced neuron-like morphological changes. Since neuroendocrine differentiation
is observed in most prostate carcinomas, these findings raise the possibility
that IL-6 may be involved in neuroendocrine differentiation in vivo.
PMID- 10198260
TI - Human very-long-chain acyl-CoA synthetase: cloning, topography, and relevance to
branched-chain fatty acid metabolism.
AB - Very-long-chain acyl-CoA synthetases (VLCS) activate very-long-chain fatty acids
(VLCFA) containing 22 or more carbons to their CoA derivatives. We cloned the
human ortholog (hVLCS) of the gene encoding the rat liver enzyme (rVLCS). Both
hVLCS and rVLCS contain 620 amino acids, are expressed primarily in liver and
kidney, and have a potential peroxisome targeting signal 1 (-LKL) at their
carboxy termini. When expressed in COS-1 cells, hVLCS activated the VLCFA
lignoceric acid (C24:0), a long-chain fatty acid (C16:0), and two branched-chain
fatty acids, phytanic acid and pristanic acid. Immunofluorescence and immunoblot
studies localized hVLCS to both peroxisomes and endoplasmic reticulum. In
peroxisomes of HepG2 cells, hVLCS was topographically oriented facing the matrix
and not the cytoplasm. This orientation, coupled with the observation that hVLCS
activates branched-chain fatty acids, suggests that hVLCS could play a role in
the intraperoxisomal reactivation of pristanic acid produced via alpha-oxidation
of phytanic acid.
PMID- 10198261
TI - Glucose metabolic alterations in isolated and perfused rat hepatocytes induced by
pancreatic cancer conditioned medium: a low molecular weight factor possibly
involved.
AB - A serious insulin resistance characterizes pancreatic cancer-associated diabetes
mellitus. Elsewhere, we demonstrated that MIA PaCa2 cultured cells secrete a
soluble factor responsible for reduced glucose tolerance induced in SCID mice.
The intracellular mechanism of insulin resistance was investigated in isolated
and perfused rat hepatocytes incubated with MIA PaCa2 conditioned medium. Lactate
production was reduced compared to hepatocytes incubated with control medium
while 1,2-DAG was increased and PKC was activated in the hepatocytes incubated
with MIA PaCa2 conditioned medium. This behavior was not reproduced treating the
hepatocytes with the growth factors EGF, interleukin Ibeta, interleukin-6, and
TGF-beta1. In an attempt to make a biochemical identification of the hypothesized
tumor associated-diabetogenic factors we observed a low molecular weight protein
in the conditioned medium, absent in the nonconditioned one, that may be
responsible for the described behaviors.
PMID- 10198262
TI - Evidence for cooperative binding of (-)Isoproterenol to rat brain beta1
adrenergic receptors.
AB - In the present study, the effects of the thiol oxidising agent diamide upon the
properties of rat brain beta1-adrenergic and human platelet serotonin2A receptor
recognition sites have been investigated using [3H](-)CGP-12177 (in the presence
of ICI-118551) and [3H]LSD as ligands. (-)Isoprenaline inhibited [3H](-)CGP-12177
binding with nH values of 0.87, 0.67, and 0.56 for added Mg2+ concentrations of
0, 2.5, and 25 mM, respectively. Pretreatment with diamide increased the nH to
above unity for the inhibition of the binding by (-)isoprenaline, without a
concomitant effect on the inhibition of the binding by (-)propranolol. In
contrast, diamide reduced the affinity of human platelet serotonin2A-receptors
for antagonists, but did not consistently induce nH values above unity for the
inhibition of antagonist binding by serotonin. These results suggest that
cooperative interactions reported for cardiac muscarinic receptors may also occur
for beta1-adrenergic receptors in the rat brain.
PMID- 10198263
TI - Interferon-gamma, bacterial lipopolysaccharide, and tumor necrosis factor-alpha
induce CD11a mRNA and protein via Na+/H+ exchange and protein kinase C-dependent
mechanisms in tissue macrophages.
AB - Previously CD11a or leukocyte function-associated antigen alpha-1 was found to be
induced at the surface protein level in thioglycolate-elicited peritoneal
macrophages by bacterial lipopolysaccharide and interferon-gamma. To investigate
this induction further, Northern blotting and enzyme-linked immunosorbent assays
were used to examine the role of second messengers in CD11a gene product
induction by these agents. Here I report that CD11a RNA and cell surface protein
induced by bacterial lipopolysaccharide and tumor necrosis factor-alpha are
sensitive to inhibition of protein kinase C, while insensitive to inhibition of
Na+/H+ exchange. CD11a induction by interferon-gamma conversely is sensitive to
inhibition of Na+/H+ exchange and insensitive to inhibition of protein kinase C.
These observations indicate that CD11a may be induced by multiple and separate
second messenger systems in primary macrophages.
PMID- 10198273
TI - Disruption of androgen-regulated male reproductive development by di(n-butyl)
phthalate during late gestation in rats is different from flutamide.
AB - Gestational and lactational exposure to di(n-butyl) phthalate (DBP) at >/=250
mg/kg/day disrupts male rat reproductive development and function. Although this
indicates an antiandrogenic mechanism, DBP and its biologically active metabolite
do not interact with the androgen receptor (AR) in vitro. In the present study,
we compared the effects of DBP and the antiandrogen flutamide using a shorter
exposure during the prenatal period of male sexual differentiation in rats.
Pregnant CD rats received DBP at 0, 100, 250, or 500 mg/kg/day po (n = 10) or
flutamide at 100 mg/kg/day po (n = 5) from Gestation Days 12 to 21. In F1 males,
DBP (500 mg/kg/day) and flutamide caused hypospadias; cryptorchidism; agenesis of
the prostate, epididymis, and vas deferens; degeneration of the seminiferous
epithelium; and interstitial cell hyperplasia of the testis. Flutamide and DBP
(250 and 500 mg/kg/day) also produced retained thoracic nipples and decreased
anogenital distance. Interstitial cell adenoma occurred at 500 mg DBP/kg/day in
two males. The only effect seen at 100 mg DBP/kg/day was delayed preputial
separation. In contrast to flutamide, DBP caused a low incidence of prostate
agenesis and hypospadias with no vaginal pouch. The low incidence of DBP-induced
intraabdominal testes contrasted with the high incidence of inguinal testes seen
with flutamide. Thus prenatal male sexual differentiation is a sensitive period
for the reproductive toxicity of DBP. A no observed adverse effect level was not
established and the lowest observed (adverse) effect level was 100 mg/kg/day.
Flutamide and DBP disrupted the androgen signaling necessary for male sexual
differentiation but with a different pattern of antiandrogenic effects. DBP is an
example of an environmental antiandrogen that disrupts androgen-regulated male
sexual differentiation without interacting directly with the AR, as does
flutamide.
PMID- 10198274
TI - Quantification of total oxidant scavenging capacity of antioxidants for
peroxynitrite, peroxyl radicals, and hydroxyl radicals.
AB - We have extended the application of our previously reported total oxidant
scavenging capacity (TOSC) assay (Winston et al., Free Radical Biol. Med. 24, 480
493, 1998) to permit facile quantification of the absorbance capacity of
antioxidants toward three potent oxidants, i.e., hydroxyl radicals, peroxyl
radicals, and peroxynitrite. Respectively, these oxidants were generated by the
iron plus ascorbate-driven Fenton reaction, thermal homolysis of 2,2'-azobis(2
methylpropionamidine) dihydrochloride (ABAP), and 3-morpholinosydnonimine N
ethylcarbamide (SIN-1). Each of these oxidants reacts with alpha-keto-gamma
methiolbutyric acid (KMBA), which is oxidized and yields ethylene. The
antioxidant capacity of the compounds tested is quantified from their ability to
inhibit ethylene formation relative to a control reaction. Assay conditions were
established in which control reactions give comparable yields of ethylene with
each of the oxidants studied. Thus, the relative efficiency of various
antioxidants could be compared under conditions of quantitatively similar KMBA
oxidizing capability by the three oxidants. Reduced glutathione was an efficient
scavenger of peroxyl radicals, but scavenged peroxynitrite and hydroxyl radicals
relatively poorly. Uric acid, Trolox, and ascorbic acid were comparable
scavengers of peroxynitrite and peroxyl radicals. Uric acid and Trolox were
approximately an order of magnitude less efficient as scavengers of hydroxyl
radicals. The classical hydroxyl radical scavenging agents mannitol, dimethyl
sulfoxide, and benzoic acid had much higher TOSC values with hydroxyl than with
peroxyl radicals or peroxynitrite. The very different chemical reactivity toward
KMBA by the SIN-1- and iron-ascorbate-generated oxidants indicates that hydroxyl
radical is not a major oxidant produced by the SIN-1 system. The data show that
the TOSC assay is useful and robust in distinguishing the reactivity of various
oxidants and the relative capacities of antioxidants to scavenge these oxidants.
PMID- 10198275
TI - p53 is not inactivated in B6C3F1 mouse vascular tumors arising spontaneously or
associated with long-term administration of the thiazolidinedione troglitazone.
AB - Hemangiomas and hemangiosarcomas are uncommon in rodents and humans and, as such,
the mechanisms giving rise to these tumors are poorly understood. Inactivating
mutations in the p53 gene have been detected in sporadic and chemically induced
human and rodent hemangiosarcomas. Additionally, experimental ablation of p53
function in mice by targeted gene disruption increases the incidence of both
spontaneous and carcinogen-induced vascular tumors. These findings implicate p53
disruption in vascular tumor development. In this study, we characterized p53
inactivation immunocytochemically and by gene sequencing in a large number of
vascular tumors that developed in B6C3F1 mice during a long-term (2-year) study
of the thiazolidinedione troglitazone. For comparative purposes, a murine
hemangiosarcoma induced by polyoma middle-T antigen, which transforms endothelial
cells via a p53-independent mechanism, five spontaneous human hemangiosarcoma
specimens, and species-specific positive control tissues were also evaluated by
immunocytochemistry for p53 inactivation. While 20% of the human hemangiosarcomas
and all positive control tissues expressed significant levels of nuclear p53,
indicating functional inactivation of the protein, none of the 161 mouse vascular
tumors studied expressed detectable p53 protein. The absence of inactivating
mutations was confirmed in eight of the histologically most malignant mouse
hemangiosarcomas by sequencing exons 5 to 8 of the p53 gene. These results
demonstrate that p53 inactivation did not play a role in development of the
vascular tumors seen in the long-term study of troglitazone, and they indicate
that loss of p53 function is not essential for vascular tumor development in
mice.
PMID- 10198276
TI - Effects of mercury on the isolated heart muscle are prevented by DTT and
cysteine.
AB - The protective effects of dithiothreitol (DTT, 50 microM) and cysteine (CYS, 100
microM) against toxic effects of HgCl2 (1, 2.5, 5, and 10 microM) were studied in
isolated, isometrically contracting rat papillary muscles. Force reduction
promoted by Hg2+ was prevented by both DTT and CYS. Also, after both treatments,
no significant changes in dF/dt were observed. A progressive reduction in the
time to peak tension was observed when increased concentrations of HgCl2 were
used after CYS and DTT treatment. This was an indication that the enhancement of
calcium release from the sarcoplasmic reticulum produced by mercury was not
affected by DTT and CYS. Tetanic contractions were also studied. After treatment
with DTT or CYS tetanic tension did not change. No significant reduction of
tetanic tension was observed during treatment with 1 microM Hg2+ but its
reduction was observed after 5 microM Hg2+. Myosin ATPase activity was also
affect by Hg2+, being completely blocked by 1 microM Hg2+ and reduced by 50% with
0.15 microM Hg2+. Full activity was restored by using 500 nM DTT. These findings
suggest that several but not all toxic effects of Hg2+ on the mechanical activity
of the heart muscle are prevented by protectors of SH groups such as DTT and CYS.
The enhancement of the Ca2+ release from the sarcoplasmic reticulum by Hg2+
during activation was not affected by prior treatment with DTT and CYS,
suggesting that interactions with SH groups may not be important for the
activation of the Ca2+ channel of the sarcoplasmic reticulum.
PMID- 10198277
TI - Transport of manganese via the olfactory pathway in rats: dosage dependency of
the uptake and subcellular distribution of the metal in the olfactory epithelium
and the brain.
AB - The dosage dependency of the uptake of Mn from the olfactory epithelium via
olfactory neurons into the brain was studied after intranasal administration of
the metal in rats. The results indicate that the Mn transport is saturable both
regarding the uptake into the olfactory epithelium and the transfer to the
olfactory bulb. Further, our data indicate that Mn moves relatively freely from
the olfactory bulb to the olfactory cortex at an amount dependent on the level of
influx into the bulb. The transport to the rest of the brain was related to the
amounts in the olfactory bulb and the olfactory cortex, but the relative
proportion reaching this area increased with increasing doses. Cell
fractionations showed that the Mn was present both in the cytosol and in
association with various cell constituents. Gel filtrations of the cytosol on a
Superdex 30 column showed that about 20% of the Mn in the brain and about 3% in
the olfactory epithelium was eluted together with high-molecular-weight materials
(MW > 10,000), whereas the rest was eluted in the total volume and may represent
unbound metal. It is likely that the metal has been loosely associated with
protein(s) or other constituents at the application to the column, but that this
association is too loose to be retained during the passage through the column.
Our results show that the olfactory neurons provide a pathway with a considerable
capacity to transport Mn into the brain. We propose that the neurotoxicity of
inhaled Mn is related to an uptake via this route.
PMID- 10198278
TI - Interactions of macrolide antibiotics (Erythromycin A, roxithromycin,
erythromycylamine [Dirithromycin], and azithromycin) with phospholipids: computer
aided conformational analysis and studies on acellular and cell culture models.
AB - The potential of 14/15 membered macrolides to cause phospholipidosis has been
prospectively assessed, and structure-effects examined, using combined
experimental and conformational approaches. Biochemical studies demonstrated drug
binding to phosphatidylinositol-containing liposomes and inhibition of the
activity of lysosomal phospholipase A1 toward phosphatidylcholine included in the
bilayer, in close correlation with the number of cationic groups carried by the
drugs (erythromycin A = roxithromycin < erythromycylamine = azithromycin). In
cultured cells (fibroblasts), phospholipidosis (affecting all major phospholipids
except sphingomyelin) was observed after 3 days with the following ranking:
erythromycin A = roxithromycin < erythromycylamine < azithromycin
(roxithromycin could, however, not be studied in detail due to intrinsic
toxicity). The difference between erythromycylamine and azithromycin was
accounted for by the lower cellular accumulation of erythromycylamine. In
parallel, based on a methodology developed and validated to study drug-membrane
interactions, the conformational analyses revealed that erythromycin A,
roxithromycin, erythromycylamine, and azithromycin penetrate into the hydrophobic
domain of a phosphatidylinositol monolayer through their desosamine and cladinose
moieties, whereas their macrocycle is found close to the interface. This position
allows the aminogroups carried by the macrocycle of the diaminated macrolides
(erythromycylamine and azithromycin) to come into close contact with the
negatively charged phosphogroup of phosphatidylinositol, whereas the amine
located on the C-3 of the desosamine, common to all four drugs, is located at a
greater distance from this phosphogroup. Our study suggests that all macrolides
have the potential to cause phospholipidosis but that this effect is modulated by
toxicodynamic and toxicokinetic parameters related to the drug structure and
mainly to their cationic character.
PMID- 10198279
TI - Caspase involvement in the induction of apoptosis by the environmental toxicants
tributyltin and triphenyltin.
AB - Organotin compounds such as tributyltin (TBT) and triphenyltin (TPT) can kill
target cells by triggering apoptosis. The mechanism by which these environmental
toxicants activate the apoptotic program is currently unclear. We have studied
the effect of TBT and TPT in the human Hut-78 and Jurkat T-lymphocyte cell lines.
Within 1 h there was a 30-fold increase in caspase activity, as measured by the
cleavage of the fluorescent peptide DEVD-AMC. Morphological changes
characteristic of apoptosis, such as membrane blebbing and nuclear fragmentation,
were readily detectable. Blocking caspase activity with the peptide inhibitor z
VAD-fmk prevented all subsequent apoptotic changes. The optimal concentration
range for induction of apoptosis was 0.5 to 5 microM TBT. TPT was also able to
trigger caspase activity in the lymphocyte cell lines, but it took over 2 h to
detect and occurred at a lower concentration range of 0.01 to 1 microM. Higher
concentrations of TBT and TPT caused cell necrosis, and we showed that these
concentrations were able to inhibit caspase activity in apoptotic cells. TBT and
TPT were able interact with a vicinal thiol compound, similar to the known
caspase inhibitor phenylarsine oxide, providing a potential mechanism for caspase
inhibition. We propose that vicinal thiol proteins may be a general biological
target of these organotin compounds, leading to the induction of caspase activity
and apoptosis at low concentrations, and more extensive cell damage and necrotic
cell death at higher concentrations.
PMID- 10198280
TI - Toxicity of 3,3',4,4'-tetrachloroazobenzene in rats and mice.
AB - The toxicity of 3,3',4,4'-tetrachloroazobenzene (TCAB) was evaluated in 13-week
gavage studies in male and female F344/N rats and B6C3F1 mice. In addition to
histopathology, evaluations included clinical chemistry, hematology, thyroid
hormone analyses, and reproductive parameters. Groups of 10 rats and 10 mice of
each sex were exposed to TCAB at dose levels of 0, 0.1, 1, 3, 10, or 30 mg/kg for
5 days a week for 13 weeks. In the rat studies, the major effects for both males
and females included a 10% decrease in terminal body weight at 30 mg/kg/day, an
increase in hematopoietic cell proliferation in the spleen at 10 and 30
mg/kg/day, and a responsive anemia at 10 and 30 mg/kg/day. A 15 to 30% decrease
in platelet counts and a 20 to 40% decrease in thymus weights was observed at 10
and 30 mg/kg/day. An increase in liver weight up to 15% was found at 3 mg/kg/day
and higher doses in males and at 10 and 30 mg/kg/day in females, respectively. An
increase in spleen weights up to 15% was observed at 10 and 30 mg/kg/day in males
and at 30 mg/kg/day in females. A marked decrease in circulating total thyroxine
(TT4) was found in both males and females at all dose levels tested. TT4 could
hardly be detected at 10 and 30 mg TCAB/kg/day. In addition, hyperplasia of the
forestomach was increased at 3 mg/kg/day and higher doses in males and at 30
mg/kg/day in females. In the mouse studies, an increase in liver and spleen
weight was observed up to approximately 25% in both males and females at 10 and
30 mg/kg/day. Hyperplasia of the forestomach was observed at 1 mg/kg/day and
higher doses in both males and females. In males, a 30% decrease in thymus
weights at 30 mg/kg/day and a 60% decrease in epididymal sperm density at 3 and
30 mg/kg/day was observed. Also in males, centrilobular hypertrophy of
hepatocytes and an increase in hematopoietic cell proliferation in the spleen was
observed at 3 mg/kg/day and higher doses. Based on the current study and
information in the literature, TCAB has dioxin-like properties. Comparison of the
effects of TCAB in the present study and in the literature to those with 2,3,7, 8
tetrachlorodibenzo-p-dioxin (TCDD) indicates that TCAB is from two to six orders
of magnitude less potent than TCDD depending on the end point.
PMID- 10198281
TI - Dynamic distribution and formation of a para-sarcomeric banding pattern of
prosomes during myogenic differentiation of satellite cells in vitro.
AB - Myogenesis proceeds by fusion of proliferating myoblasts into myotubes under the
control of various transcription factors. In adult skeletal muscle, myogenic stem
cells are represented by the satellite cells which can be cultured and
differentiate in vitro. This system was used to investigate the subcellular
distribution of a particular type of prosomes at different steps of the myogenic
process. Prosomes constitute the MCP core of the 26S proteasomes but were first
observed as subcomplexes of the untranslated mRNPs; recently, their RNase
activity was discovered. A monoclonal antibody raised against the p27K subunit
showed that the p27K subunit-specific prosomes move transiently into the nucleus
prior to the onset of myoblast fusion into myotubes; this represents possibly one
of the first signs of myoblast switching into the differentiation pathway. Prior
to fusion, the prosomes containing the p27K subunit return to the cytoplasm,
where they align with the gradually formed lengthwise-running desmin-type
intermediate filaments and the microfilaments, co-localizing finally with the
actin bundles. The prosomes progressively form discontinuous punctate structures
which eventually develop a pseudo-sarcomeric banding pattern. In myotubes just
formed in vitro, the formation of this pattern seems to preceed that produced by
the muscle-specific sarcomeric (alpha)-actin. Interestingly, this pattern of
prosomes of myotubes in terminal in vitro differentiation was very similar to
that of prosomes observed in vivo in foetal and adult muscle. These observations
are discussed in relation to molecular myogenesis and prosome/proteasome
function.
PMID- 10198282
TI - The conjusome: a novel structure in Tetrahymena found only during sexual
reorganization.
AB - A unique structure, the conjusome, has been identified and initially
characterized in Tetrahymena thermophila. The conjusome appears only during a
specific phase of conjugation. Immunofluorescence microscopy reveals that the
conjusome is strongly labeled by antibodies to the protein Pdd1p. Pdd1p is a
chromodomain protein and participates in the formation of chromatin-containing
structures in developing macronuclear anlagen. Recent studies suggest that Pdd1p
is physically associated with the elimination of specific germ-line sequences
from developing macronuclei (anlagen) and may play a role in heterochromatin
assembly. The conjusome contains Pdd1p, but it is devoid of any detectable DNA.
The conjusome appears before DNA elimination begins in the developing anlagen and
after Pdd1p is found in the parental macronucleus. Transmission electron
microscopic observations reveal that the conjusome is not a membrane-bounded
structure. The conjusome ranges in size from about 1 microm to sizes approaching
7 microm, depending on its maturity. It is composed of a coarse reticulum of a
fibrous, electron dense material, interspersed with apparent background
cytoplasm. Our initial characterization does suggest a number of possible
functions for what may be a new, transient organelle.
PMID- 10198283
TI - Reactive oxygen metabolites increase mitochondrial calcium in endothelial cells:
implication of the Ca2+/Na+ exchanger.
AB - In endothelial cells, a bolus of hydrogen peroxide (H2O2) or oxygen metabolites
generated by hypoxanthine-xanthine oxidase (HX-XO) increased the mitochondrial
calcium concentration [Ca2+]m. Both agents caused a biphasic increase in [Ca2+]m
which was preceded by a rise in cytosolic free calcium concentration [Ca2+]c (18
and 6 seconds for H2O2 and HX-XO, respectively). The peak and plateau elevations
of [Ca2+] were consistently higher in the mitochondrial matrix than in the
cytosol. In Ca2+-free/EGTA medium, the plateau phase of elevated [Ca2+] evoked by
H2O2 due to capacitative Ca2+ influx was abolished in the cytosol, but was
maintained in the mitochondria. In contrast to H2O2 and HX-XO, ATP which binds
the P2Y purinoceptors induced an increase in [Ca2+]m that was similar to that of
[Ca2+]c. When cells were first stimulated with inositol 1,4, 5-trisphosphate
generating agonists or the Ca2+-ATPase inhibitor cyclopiazonic acid (CPA),
subsequent addition of H2O2 did not affect [Ca2+]c, but still caused an elevation
of [Ca2+]m. Moreover, the specific inhibitor of the mitochondrial Ca2+/Na+
exchanger, 7-chloro-3,5-dihydro-5-phenyl-1H-4.1-benzothiazepine-2-on (CGP37157),
did not potentiate the effects of H2O2 and HX-XO on [Ca2+]m, while causing a
marked increase in the peak [Ca2+]m and a significant attenuation of the rate of
[Ca2+]m efflux upon addition of histamine or CPA. In permeabilized cells, H2O2
mimicked the effects of CGP37157 causing an increase in the basal level of matrix
free Ca2+ and decreased efflux. Dissipation of the electrochemical proton
gradient by carbonylcyanide p-(trifluoromethoxy) phenylhydrazone (FCCP), and
blocade of the Ca2+ uptake by ruthenium red prevented [Ca2+]m increases evoked by
H2O2. These results demonstrate that the H2O2-induced elevation in [Ca2+]m
results from a transfer of Ca2+ secondary to increased [Ca2+]c, and an inhibition
of the Ca2+/Na+ electroneutral exchanger of the mitochondria.
PMID- 10198284
TI - Selective localization of the polytopic membrane protein prominin in microvilli
of epithelial cells - a combination of apical sorting and retention in plasma
membrane protrusions.
AB - Prominin is a recently identified polytopic membrane protein expressed in various
epithelial cells, where it is selectively associated with microvilli. When
expressed in non-epithelial cells, prominin is enriched in plasma membrane
protrusions. This raises the question of whether the selective association of
prominin with microvilli in epithelial cells is solely due to its preference for,
and stabilization in, plasma membrane protrusions, or is due to both sorting to
the apical plasma membrane domain and subsequent enrichment in plasma membrane
protrusions. To investigate this question, we have generated stably transfected
MDCK cells expressing either full-length or C-terminally truncated forms of mouse
prominin. Confocal immunofluorescence and domain-selective cell surface
biotinylation experiments on transfected MDCK cells grown on permeable supports
demonstrated the virtually exclusive apical localization of prominin at steady
state. Pulse-chase experiments in combination with domain-selective cell surface
biotinylation showed that newly synthesized prominin was directly targeted to the
apical plasma membrane domain. Immunoelectron microscopy revealed that prominin
was confined to microvilli rather than the planar region of the apical plasma
membrane. Truncation of the cytoplasmic C-terminal tail of prominin impaired
neither its apical cell surface expression nor its selective retention in
microvilli. Both the apical-specific localization of prominin and its selective
retention in microvilli were maintained when MDCK cells were cultured in low
calcium medium, i.e. in the absence of tight junctions. Taken together, our
results show that: (i) prominin contains dual targeting information, for direct
delivery to the apical plasma membrane domain and for the enrichment in the
microvillar subdomain; and (ii) this dual targeting does not require the
cytoplasmic C-terminal tail of prominin and still occurs in the absence of tight
junctions. The latter observation suggests that entry into, and retention in,
plasma membrane protrusions may play an important role in the establishment and
maintenance of the apical-basal polarity of epithelial cells.
PMID- 10198285
TI - Cell-extracellular matrix interactions and EGF are important regulators of the
basal mammary epithelial cell phenotype.
AB - The mammary epithelium is composed of a luminal epithelium and a basal layer
containing myoepithelial cells and undifferentiated precursors. Basal cells
express specific protein markers, such as keratin 14 (K14) and P-cadherin. To
study the factors that regulate the basal mammary epithelial cell phenotype, we
have established two clonal derivatives of the mouse HC11 cell line, BC20 and
BC44, expressing high levels of K14 and P-cadherin. Unlike the parental HC11
cells, these basal cells did not produce beta-casein in response to lactogenic
hormone treatment; however their phenotype appeared to be plastic. Cultured in
EGF-free medium, they exhibited enhanced cell-extracellular matrix adhesions and
deficient cell-cell junctions, whereas long-term treatment with EGF induced a
decrease of focal contact number and establishment of cell-cell junctions,
resulting in downregulation of K14 and P-cadherin expression at the protein and
mRNA levels. To determine whether cell-extracellular matrix interactions mediated
by integrins have a role in the regulation of the expression of K14 and P
cadherin, the amounts of transcripts for the two proteins were analysed in the
basal cells, which were plated on the function-blocking antibodies against beta1
and alpha6 integrin chains, on fibronectin and on laminin 5. The amount of P
cadherin transcript was 2- to 4-fold higher in cells plated on the function
blocking anti-integrin antibodies and on the extracellular matrix proteins, as
compared to cells plated on poly-L-lysine, whereas the K14 transcript levels were
not significantly modified in response to adhesion. The data demonstrate that
integrin-mediated cell interaction with extracellular matrix is directly
implicated in the control of P-cadherin expression, and that EGF and cell
extracellular matrix adhesion events are important regulators of the basal
mammary epithelial cell phenotype.
PMID- 10198286
TI - Active transgenes in zebrafish are enriched in acetylated histone H4 and
dynamically associate with RNA Pol II and splicing complexes.
AB - We have investigated the functional organization of active and silent integrated
luciferase transgenes in zebrafish, with the aim of accounting for the
variegation of transgene expression in this species. We demonstrate the
enrichment of transcriptionally active transgenes in acetylated histone H4 and
the dynamic association of the transgenes with splicing factor SC35 and RNA Pol
II. Analysis of interphase nuclei and extended chromatin fibers by
immunofluorescence and in situ hybridization reveals a co-localization of
transgenes with acetylated H4 in luciferase-expressing animals only. Enrichment
of expressed transgenes in acetylated H4 is further demonstrated by their co
precipitation from chromatin using anti-acetylated H4 antibodies. Little
correlation exists, however, between the level of histone acetylation and the
degree of transgene expression. In transgene-expressing zebrafish, most
transgenes co-localize with Pol II and SC35, whereas no such association occurs
in non-expressing individuals. Inhibition of Pol II abolishes transgene
expression and disrupts association of transgenes with SC35, although inactivated
transgenes remains enriched in acetylated histones. Exposure of embryos to the
histone deacetylation inhibitor TSA induces expression of most silent transgenes.
Chromatin containing activated transgenes becomes enriched in acetylated histones
and the transgenes recruit SC35 and Pol II. The results demonstrate a correlation
between H4 acetylation and transgene activity, and argue that active transgenes
dynamically recruit splicing factors and Pol II. The data also suggest that
dissociation of splicing factors from transgenes upon Pol II inhibition is not a
consequence of changes in H4 acetylation.
PMID- 10198287
TI - Pre-mRNA and mRNA binding of human nuclear DNA helicase II (RNA helicase A).
AB - Nuclear DNA helicase II (NDH II), alternatively named RNA helicase A, seems to
function as a pre-mRNA and mRNA binding protein in human cells.
Immunofluorescence studies of NDH II gave a highly diffused nucleoplasmic
staining that was similar to that of hnRNP A1 but differed from the localization
of the RNA splicing factor Sc-35. Upon transcriptional inhibition, NDH II
migrated from the nucleus into the cytoplasm. During mitosis, NDH II was released
into the cytoplasm during pro- to metaphase, and was gradually recruited back
into telophase nuclei. The timing of nuclear import of NDH II at telophase was
found to be later than that of hnRNP A1 but paralleled that of Sc-35. At the
ultrastructural level, both NDH II and hnRNP A1 were identified within
perichromatin ribonucleoparticle fibrils. However, the subnuclear distributions
of NDH II and hnRNP A1 were not overlapping. NDH II could be extracted together
with poly(A)-containing mRNA from HeLa cell nuclei and, to a much lesser extent,
from the cytoplasm. Following transcriptional inhibition, NDH II was
preferentially associated with mRNA from the cytosol, which biochemically
confirmed the microscopic observations. Although NDH II is mainly a nuclear
enzyme, it is apparently not associated with the nuclear matrix, since it could
be extracted with 2 M NaCl from DNase I-treated nuclei. Our cellular and
biochemical observations strongly suggest that NDH II is a pre-mRNA and mRNA
binding protein. Its significant affinity for ssDNA, but not for dsDNA, points to
a transient role in DNA binding during the process of transcript formation.
According to our model, single-stranded DNA might be necessary to retain NDH II
in the nuclear compartment.
PMID- 10198288
TI - Ultrastructural distribution of a MAP kinase and transcripts in quiescent and
cycling plant cells and pollen grains.
AB - Mitogen-activated protein kinases (MAPKs) are components of a kinase module that
plays a central role in the transduction of diverse extracellular stimuli,
including mitogens, specific differentiation and developmental signals and stress
treatments. This shows that reversible protein phosphorylation cascades play a
pivotal role in signal transduction in animal cells and yeast, particularly the
entry into mitosis of arrested cells. Homologues of MAPKs have been found and
cloned in various plant species, but there have been no data about their in situ
localization at the subcellular level and their expression in plant cells so far.
In the present paper we report the first data on the ultrastructural in situ
localization of MAPK and their mRNAs in various plant cells. Proliferating and
quiescent meristematic plant cells were studied to evaluate whether changes in
MAPK presence, distribution and expression accompany the entry into proliferation
of dormant cells. Moreover, MAPK localization was analyzed in vacuolate
microspores. Polyclonal antibodies against the deduced MAPK from the tobacco Ntf6
clone were able to recognize homologue epitopes by immunocytochemical techniques
in the cell types studied. The pattern of protein distribution is similar in all
the cases studied: it is localized in the cytoplasm and in the nucleus, mainly in
the interchromatin region. The quantitative study of the density showed that MAPK
labelling is more abundant in cycling than in quiescent cells, also suggesting
that, in plants, MAPK pathways might play a role in cell proliferation. RNA
probes for conserved regions of the catalytic domain of plant MAPK homologue
genes were used to study MAPK expression in those plant cells. In situ
hybridization (ISH) showed the presence of MAPK transcripts in the three plant
cell types studied, but levels were very low in quiescent cells compared to those
in cycling cells. The quantification of labelling density of ISH signals strongly
suggests a higher level of MAPK expression in proliferating cells, but also some
basal messenger presence and/or expression in the quiescent ones. Immunogold and
ISH results show the presence and distribution of MAPK proteins and mRNAs in
vacuolate microspores. This represents a very dynamic stage during pollen
development in which the cell nucleus is being prepared for an asymmetrical
mitotic division, giving rise to both the generative and the vegetative nuclei of
the bicellular pollen grain. Taken together, the data indicate a role played by
MAPK in the re-entry into proliferation in plant cells.
PMID- 10198289
TI - Subcellular heterogeneity of mitochondrial membrane potential: relationship with
organelle distribution and intercellular contacts in normal, hypoxic and
apoptotic cells.
AB - The subcellular heterogeneity of mitochondrial membrane potential (mDelta psi)
was investigated in confluent and sub-confluent cultures of four cell types
(human astrocytes, HEp-2, MDCK and Vero cells) in normal growth conditions,
hypoxia and apoptosis. The distribution of high-polarized mitochondria, detected
by the potential-sensitive probe JC-1, was found to depend on: (1) the proximity
to the cell edge; (2) the local absence of cell-cell contacts; and (3) the local
absence of acidic vesicles. Both hypoxia and apoptosis produced a general mDelta
psi increase with different redistributions of high-polarized mitochondria.
Hypoxic cells maintained high-polarized mitochondria for over 24 hours, until
cells underwent necrosis. On the other hand, apoptotic cells showed an unexpected
convergence of high-polarized mitochondria into an extremely packed mass at one
side of the nucleus, in a stage preceding nuclear condensation, but correlated to
the retraction of cell-cell contacts.
PMID- 10198290
TI - Mitotic control in the absence of cdc25 mitotic inducer in fission yeast.
AB - Fission yeast cells tolerate the total absence of the cdc25 mitotic inducer in
two cases, either in cdc2-3w or in wee1 genetic backgrounds. In the cdc2-3w
cdc25Delta double mutant, the rate-limiting step leading to mitosis is reaching a
critical size. However, the size control of this mutant operates in late G2,
which is different from wild-type (WT) cells. This fact suggests that in WT the
rate-limiting molecular process during the G2 timer is the Tyr15
dephosphorylation of cdc2, for which the cdc25 phosphatase (together with its
back-up, pyp3) is dependent. In the wee1-50 cdc25Delta mutant, the population
splits into different clusters, all lacking mitotic size control. This strain
maintains size homeostasis by a novel method, which is random movement of the
cells from one cluster to another in the successive generations. These cells
should normally have a 'minimal cycle', a 'timer' with short G1 and G2 phases.
However, very often the cells abort mitosis, possibly at an early event and
return back to early G2, thus lengthening their cycles. The inability of these
cells to start anaphase might be caused by the absence of the main mitotic
regulators (wee1 and cdc25) and the improper regulation of their back-up copies
(mik1 and pyp3, respectively).
PMID- 10198291
TI - Carboxy-terminal conversion of profibrillin to fibrillin at a basic site by
PACE/furin-like activity required for incorporation in the matrix.
AB - Fibrillin-1, the main component of 10-12 nm microfibrils of the extracellular
matrix, is synthesized as profibrillin and proteolytically processed to
fibrillin. The putative cleavage site has been mapped to the carboxy-terminal
domain of profibrillin-1, between amino acids arginine 2731 and serine 2732, by a
spontaneous mutation in this recognition site that prevents profibrillin
conversion. This site contains a basic amino acid recognition sequence (R-G-R-K-R
R) for proprotein convertases of the furin/PACE family. In this study, we use a
mini-profibrillin protein to confirm the cleavage in the carboxy-terminal domain
by both fibroblasts and recombinantly expressed furin/PACE, PACE4, PC1/3 and PC2.
Site-directed mutagenesis of amino acids in the consensus recognition motif
prevented conversion, thereby identifying the scissile bond and characterizing
the basic amino acids required for cleavage. Using a PACE/furin inhibitor, we
show that wild-type profibrillin is not incorporated into the extracellular
matrix until it is converted to fibrillin. Therefore, profibrillin-1 is the first
extracellular matrix protein to be shown to be a substrate for subtilisin-like
proteases, and the conversion of profibrillin to fibrillin controls
microfibrillogenesis through exclusion of uncleaved profibrillin.
PMID- 10198292
TI - Direct demonstration of the endocytic function of caveolae by a cell-free assay.
AB - The endocytic function of caveolae was challenged by taking advantage of a cell
free assay directly measuring the detachment of receptor-containing vesicles from
isolated plasma membranes. Plasma membranes from cultured cells surface-labeled
with 125I-cholera toxin (segregating in caveolae) were isolated as described
previously. Following incubation of these labeled membranes in the presence of
nucleotide(s) and cytosol, a significant proportion of the initially membrane
associated radioactivity was released into the incubation medium in sedimentable
form (14*10(6 )g). Results of biochemical, morphological, and fractionation
analysis of the material containing the released radioactivity directly
demonstrated that caveolae are plasma membrane domains involved in an endocytic
process and resulting in the formation of caveolae-derived vesicles. In addition,
these studies allowed a direct comparison of caveolae- and clathrin-coated pit
mediated endocytosis and reveal that these two processes diverge in terms of
kinetics, cytosol and nucleotide requirements as well as in terms of the density
and size of the endocytic vesicles formed.
PMID- 10198293
TI - A new decoration for nitric oxide synthase - a Zn(Cys)4 site.
AB - Intense interest in the action and synthesis of nitric oxide has fueled
structural studies of nitric oxide synthase (NOS). The monomeric and dimeric heme
domains of inducible NOS were the first NOS structures to be described. A recent
independent analysis of the corresponding heme domains from endothelial NOS
confirms most of the features found earlier and also reveals a novel Zn(Cys)4
center - a new feature for NOS.
PMID- 10198294
TI - Many LH peaks are needed to physiologically stimulate testosterone secretion:
modulation by fasting and NPY.
AB - The pulsatile luteinizing hormone (LH) and testosterone secretions were studied
during serial blood collections performed at 7-min time intervals in the male
rat. In fed rats, a discontinuous pattern of LH secretion was observed. Periods
without secretion alternated with active secretory episodes consisting in trains
of three to four LH peaks that triggered testosterone secretion usually 1-2 h
later. The magnitude of the testosterone response was not correlated with the
amplitude of the LH peaks. Isolated, single peaks of LH did not evoke clear
testosterone responses. Forty-eight hours after initiation of fasting,
testosterone secretion was markedly decreased, but integrated LH secretion was
only partly reduced. Chronic infusion of neuropeptide Y (NPY; 18 microgram/day,
icv) reduced testosterone secretion to very low levels and abolished pulsatile LH
secretion or testosterone response to isolated LH peaks. In conclusion, the
stimulation of testosterone secretion by LH necessitates several LH peaks
organized in a proper sequence, and the testosterone response is not immediate.
Low testosterone secretion in fasting rats appears to result from disappearance
of coordinated, multiple LH peaks of sufficient size. Inhibition of the
gonadotropic axis achieved by central NPY administration is due to either absence
of LH peak "clusters" or occurrence of nonfunctional single LH peaks.
PMID- 10198295
TI - TNF-binding protein ameliorates inhibition of skeletal muscle protein synthesis
during sepsis.
AB - We examined the effects of TNF-binding protein (TNFBP) on regulatory mechanisms
of muscle protein synthesis during sepsis in four groups of rats: Control;
Control+TNFBP; Septic; and Septic+TNFBP. Saline (1. 0 ml) or TNFBP (1 mg/kg, 1.0
ml) was injected daily starting 4 h before the induction of sepsis. The effect of
TNFBP on gastrocnemius weight, protein content, and the rate of protein synthesis
was examined 5 days later. Sepsis reduced the rate of protein synthesis by 35%
relative to controls by depressing translational efficiency. Decreases in protein
synthesis were accompanied by similar reductions in protein content and muscle
weight. Treatment of septic animals with TNFBP for 5 days prevented the sepsis
induced inhibition of protein synthesis and restored translational efficiency to
control values. TNFBP treatment of Control rats for 5 days was without effect on
muscle protein content or protein synthesis. We also assessed potential
mechanisms regulating translational efficiency. The phosphorylation state of
p70(S6) kinase was not altered by sepsis. Sepsis reduced the gastrocnemius
content of eukaryotic initiation factor 2Bepsilon (eIF2Bepsilon), but not
eIF2alpha. The decrease in eIF2Bepsilon content was prevented by treatment of
septic rats with TNFBP. TNFBP ameliorates the sepsis-induced changes in protein
metabolism in gastrocnemius, indicating a role for TNF in the septic process. The
data suggest that TNF may impair muscle protein synthesis by reducing expression
of specific initiation factors during sepsis.
PMID- 10198296
TI - Depression of liver protein synthesis during surgery is prevented by growth
hormone.
AB - This study was undertaken to elucidate the specific effects of growth hormone
(GH) on liver protein metabolism in humans during surgery. Otherwise healthy
patients scheduled for elective laparoscopic cholecystectomy were randomized into
controls (n = 9) or pretreatment with 12 units of GH for 1 day (GH 1, n = 9) or
daily for 5 days (GH 5, n = 10). The fractional synthesis rate of liver proteins,
as assessed by flooding with [2H5]phenylalanine, was higher in the GH 5 group
(22.0 +/- 6.9%/day, mean +/- SD, P < 0.05) than in the control (16.1 +/-
3.1%/day) and GH 1 (16.5 +/- 5.5%/day) groups. During surgery, the fraction of
polyribosomes in the liver, as assessed by ribosome analysis, decreased in the
control group by approximately 12% (P < 0.01) but did not decrease in the GH
treated groups. In addition, the concentrations of the essential amino acids and
aspartate in the liver decreased in response to GH treatment. In conclusion, GH
pretreatment decreases hepatic free amino acid concentrations and preserves liver
protein synthesis during surgery.
PMID- 10198297
TI - Postexercise net protein synthesis in human muscle from orally administered amino
acids.
AB - We examined the response of net muscle protein synthesis to ingestion of amino
acids after a bout of resistance exercise. A primed, constant infusion of L-[ring
2H5]phenylalanine was used to measure net muscle protein balance in three male
and three female volunteers on three occasions. Subjects consumed in random order
1 liter of 1) a mixed amino acid (40 g) solution (MAA), 2) an essential amino
acid (40 g) solution (EAA), and 3) a placebo solution (PLA). Arterial amino acid
concentrations increased approximately 150-640% above baseline during ingestion
of MAA and EAA. Net muscle protein balance was significantly increased from
negative during PLA ingestion (-50 +/- 23 nmol. min-1. 100 ml leg volume-1) to
positive during MAA ingestion (17 +/- 13 nmol. min-1. 100 ml leg volume-1) and
EAA (29 +/- 14 nmol. min-1. 100 ml leg volume-1; P < 0.05). Because net balance
was similar for MAA and EAA, it does not appear necessary to include nonessential
amino acids in a formulation designed to elicit an anabolic response from muscle
after exercise. We concluded that ingestion of oral essential amino acids results
in a change from net muscle protein degradation to net muscle protein synthesis
after heavy resistance exercise in humans similar to that seen when the amino
acids were infused.
PMID- 10198298
TI - Mechanism of adipose tissue iNOS induction in endotoxemia.
AB - The aim of the present study was to investigate the mechanism of adipose tissue
inducible nitric oxide synthase (iNOS) induction in endotoxemia. Systemic
administration of the bacterial endotoxin lipopolysaccharide (LPS) to rats for
=8 h markedly increased iNOS mRNA and protein levels in white and brown adipose
tissues. This effect was comparable to or greater than the induction of iNOS in
liver, kidney, or skeletal muscle. iNOS activity was also found to be greatly
enhanced in both white and brown adipose tissues of LPS-treated rats (an
approximately 12- to 20-fold increase). Treatment of cultured 3T3-L1 adipocytes
with LPS, tumor necrosis factor-alpha (TNF-alpha), or interferon-gamma (IFN
gamma) alone failed to induce iNOS activity. However, when used in combination,
TNF-alpha, IFN-gamma, and LPS markedly and synergistically increased iNOS
activity in these cells. In conclusion, these results suggest that adipose tissue
is a major site of iNOS expression in endotoxemia. Our data further indicate that
iNOS induction can be reproduced in vitro in cultured adipocytes and that a
concerted action of cytokines and endotoxin is needed for maximal activation of
the enzyme.
PMID- 10198299
TI - Muscle contractile activity increases fatty acid metabolism and transport and
FAT/CD36.
AB - We have examined whether 1) fatty acid (FA) uptake, 2) FA transporter expression,
and 3) FA metabolism are increased when the oxidative capacity of skeletal muscle
is increased. The oxidative capacities of red and white tibialis anterior and
extensor digitorum longus muscles were increased via chronic stimulation (10 Hz,
24 h/day for 7 days). The contralateral muscles served as controls. After 7 days
of increased muscle activity 1) palmitate uptake by giant sarcolemmal vesicles
was increased twofold (P < 0.05), 2) the expression of FA translocase (FAT)/CD36
was increased at both the mRNA (3.2- to 10-fold) and protein (3.4-fold) levels,
and 3) palmitate oxidation and esterification into triacylglycerols and
phospholipids were increased 1.5-, 2.7-, and 1.7-fold, respectively (P < 0.05).
These data show that when the oxidative capacity of muscle is increased, there is
a parallel increase in the rate of FA transport and FA transporters at the
sarcolemmal membrane, which is associated with the enhanced expression of the
membrane transporter FAT/CD36.
PMID- 10198300
TI - Plasma leptin levels and triglyceride secretion rates in VMH-lesioned obese rats:
a role of adiposity.
AB - To explore the role of adiposity on hypertriglyceridemia associated with obesity,
we examined the relation between triglyceride secretion rate (TGSR) and plasma
leptin, insulin, or insulin resistance in ventromedial hypothalamus (VMH)
lesioned rats in the dynamic and static phases (2 and 14 wk after lesions,
respectively). VMH-lesioned rats gained body weight (BW) at fivefold higher rates
in the dynamic phase compared with sham-operated control (sham) rats, and BW gain
reached a plateau in the static phase. Parametrial fat pad mass was increased 2.5
fold in VMH-lesioned rats compared with sham rats in both phases. Leptin levels
were sixfold higher in VMH-lesioned rats of the dynamic phase and even higher in
the static phase. Insulin levels were twofold higher in VMH-lesioned rats than in
sham rats in both phases. In the dynamic phase, VMH-lesioned rats had 2-fold
higher plasma triglyceride (TG) levels and 2.6-fold higher TGSRs, whereas steady
state plasma glucose (SSPG) values, an indicator of insulin resistance, were
lower. SSPG values became significantly higher in VMH-lesioned rats in the static
phase, but TGSR was not further accelerated. TGSR was significantly associated
with leptin, independent of insulin. Leptin was highly correlated with BW, fat
mass, and nonesterified fatty acids (NEFA). These results suggest that adiposity
itself plays a critical role in TGSR probably through increased NEFA flux from
enlarged adipose tissues. Insulin resistance is not associated with the
overproduction of TG in this animal model for obesity.
PMID- 10198301
TI - Serum leptin concentrations and their relation to metabolic abnormalities in
human sepsis.
AB - Circulating leptin concentrations are raised in animal models of inflammation and
sepsis. The purpose of this study was to determine the effect of sepsis on serum
leptin concentration in humans and to examine the relationship between leptin and
the metabolic consequences of sepsis. Resting energy expenditure, insulin
sensitivity, and fasting serum leptin, plasma insulin, and cortisol
concentrations were measured in 20 subjects with intra-abdominal sepsis and 20
healthy control subjects, before and during a 2-h period of euglycemic
hyperinsulinemia. Fasting serum leptin concentrations were similar in septic and
control subjects. In simple regression analysis, serum leptin concentrations
correlated significantly with percent body fat in both septic patients (r = 0.
64, P < 0.005) and healthy subjects (r = 0.75, P < 0.0001). Multiple regression
analyses additionally indicated that percent body fat, fasting plasma insulin,
and plasma cortisol, but not sepsis, were significant and independent
determinants of serum leptin concentration. No relationship between leptin and
resting energy expenditure or insulin sensitivity was identifiable. A major
metabolic role for leptin in human sepsis therefore appears unlikely.
PMID- 10198302
TI - Clearance of IGFs and insulin from wounds: effect of IGF-binding protein
interactions.
AB - We have examined the role binding proteins have in regulating the clearance of
exogenous growth factors from wounds. Hunt-Schilling chambers were subcutaneously
implanted in rats, and the clearance of insulin-like growth factor (IGF) I from
the chamber wound fluid was compared with IGF-II, LR3-IGF-I, which binds poorly
to IGF-binding proteins (IGFBP), or insulin. Elimination rate constants of the
slow phase of the decay curves did not differ between IGF-I and IGF-II. However,
LR3-IGF-I and insulin were cleared more rapidly from wound fluid than IGF-I so
that the half-lives for IGF-I, IGF-II, LR3-IGF-I, and insulin were 872, 861, 563,
and 324 min, respectively. In wound fluid, minimal degradation of the IGFs
occurred, whereas insulin was degraded considerably. The increased clearance of
LR3-IGF-I and insulin equated with a reduced association with wound fluid IGFBPs,
and increased amounts of radioactivity of these peptides were detected in the
circulation and urine. These results show that this model of wound repair may be
of use in examining the kinetics of growth factors and other bioactive molecules
in extravascular spaces and support the hypothesis that IGFBPs can be significant
regulators of IGF bioavailability in vivo.
PMID- 10198303
TI - Carbohydrate ingestion can completely suppress endogenous glucose production
during exercise.
AB - The purposes of this study were 1) to investigate the effect of carbohydrate
(CHO) ingestion on endogenous glucose production (EGP) during prolonged exercise,
2) to study whether glucose appearance in the circulation could be a limiting
factor for exogenous CHO oxidation, and 3) to investigate whether large CHO
feedings can reduce muscle glycogen oxidation during exercise. Six well-trained
subjects exercised three times for 120 min at 50% maximum workload while
ingesting water (FAST), a 4% glucose solution (LO-Glc), or a 22% glucose solution
(HI-Glc). A primed continuous intravenous [6, 6-2H2]glucose infusion was given,
and the ingested glucose was enriched with [U-13C]glucose. Glucose ingestion
significantly elevated CHO oxidation as well as the rates of appearance (Ra) and
disappearance. Ra glucose equaled Ra of glucose in gut (Ra gut) during HI-Glc,
whereas EGP was completely suppressed. During LO-Glc, EGP was partially
suppressed, whereas Ra gut provided most of the total glucose Ra. We conclude
that 1) high rates of CHO ingestion can completely block EGP, 2) Ra gut may be a
limiting factor for exogenous CHO oxidation, and 3) muscle glycogen oxidation was
not reduced by large glucose feedings.
PMID- 10198304
TI - Antioxidants reversibly inhibit the spontaneous resumption of meiosis.
AB - We previously showed that the cell-permeant antioxidant 2(3)-tert-butyl-4
hydroxyanisole (BHA) inhibited germinal vesicle breakdown (GVBD) in oocyte
cumulus complexes (OCC) of the rat. The objective of the present studies was to
assess other antioxidants and whether such inhibition was reversible. Spontaneous
GVBD in OCC incubated for 2 h was significantly inhibited (P < 0.005) by
nordihydroguaiaretic acid (NDGA; GVBD = 19.4%), BHA (GVBD = 25.7%), octyl gallate
(OG; GVBD = 52.2%), ethoxyquin (EQ; GVBD = 58.8%), 2, 6-di-tert-butyl
hydroxymethyl phenol (TBHMP; GVBD = 59%), butylated hydroxytoluene (BHT; GVBD =
59.5%), and tert-butyl hydroperoxide (TBHP; GVBD = 60.0%). Other antioxidants
that produced lower but significant (P < 0.05) inhibition of oocyte maturation
included propyl gallate (PG; GVBD = 70.3%), 2,4,5-trihydroxybutrophenone (THBP;
GVBD = 71.4%), and lauryl gallate (LG; GVBD = 71.4%). Antioxidants that had no
effect on oocyte maturation at the same concentration (100 microM) included
ascorbic acid, vitamin E, and Trolox. Inhibition of GVBD was evident for up to 8
h of incubation of OCC and denuded oocytes (DO) with BHA or NDGA and was reversed
by washing. NDGA was less potent than BHA for inhibition of GVBD in DO, unlike
that seen with OCC. Oocyte maturation was induced by incubation of follicles for
3 h with human chorionic gonadotropin (hCG), and this response was inhibited by
BHA or NDGA. These findings support the conclusion that cell-permeant
antioxidants inhibit spontaneous resumption of meiosis, which may implicate a
role of oxygen radicals in oocyte maturation.
PMID- 10198305
TI - Stimulation by 2-deoxy-D-glucose tetraacetates of hormonal secretion from the
perfused rat pancreas.
AB - The effects of alpha- and beta-2-deoxy-D-glucose tetraacetate (1.7 and 8.5 mM) on
insulin, somatostatin, and glucagon secretion from isolated rat pancreases
perfused in the presence of 8.3 mM D-glucose were compared with those of
unesterified 2-deoxy-D-glucose tested at the same two concentrations. The
unesterified glucose analog caused, in a concentration-related manner, inhibition
of glucose-induced insulin and somatostatin release and augmentation of glucagon
secretion. The two anomers of 2-deoxy-D-glucose tetraacetate, however, increased
the secretion rate of all three hormones; this effect was also related to the
concentration of the esters. No obvious anomeric specificity of the secretory
response to 2-deoxy-D-glucose tetraacetate was observed. These findings indicate
that the insulinotropic action of hexose esters cannot be accounted for solely by
the metabolic effect of their glucidic moieties. They suggest that the A, B, and
D cells of the endocrine pancreas are each equipped with a receptor system
responsible for the direct recognition of monosaccharide esters as secretagogues.
They further support the view that a paracrine effect of insulin on glucagon
producing cells does not represent a major component in the regulation of their
secretory activity.
PMID- 10198306
TI - Cyclic stretch regulates autocrine IGF-I in vascular smooth muscle cells:
implications in vascular hyperplasia.
AB - Vascular smooth muscle cells (VSMC) subjected to acute or chronic stretch display
enhanced growth rates in vitro and in vivo. Clinical examples of vascular
hyperplasia (e.g., systolic hypertension and postinjury restenosis) suggest that
local insulin-like growth factor I (IGF-I) expression is enhanced. Therefore, we
investigated the role of in vitro cyclic stretch on rat VSMC IGF-I secretion and
cellular growth. In serum-free medium, cyclic stretch (1 Hz at 120% resting
length for 48 h) stimulated thymidine incorporation approximately 40% above that
seen in nonstretched cells. Graded stretch magnitude (100-125% resting length)
yielded graded increases in VSMC growth. Exogenous IGF-I increased growth of
serum-starved, nonstretched VSMC in a dose-dependent manner, with maximal growth
seen with 10(-7) M. IGF-I secretion from stretched cells was 20- to 30-fold
greater than from those cells cultured in a static environment. Stretch-induced
increases in growth were completely blocked on addition of anti-IGF-I and
partially blocked with platelet-derived growth factor (PDGF) antibodies and with
a tyrosine kinase inhibitor (tyrphostin-1). Finally, blockade of stretch
activated cation channels with GdCl3 profoundly inhibited stretch-induced growth.
We conclude that stretch increases VSMC IGF-I secretion and that such autocrine
IGF-I is required for stretch-induced growth. PDGF and stretch-sensitive cation
channels are likely additional components of a complex pathway that regulates
stretch-induced VSMC seen in systolic hypertension and postinjury restenosis.
PMID- 10198307
TI - Insulin action on heart and skeletal muscle glucose uptake in weight lifters and
endurance athletes.
AB - There are no studies comparing myocardial metabolism between endurance- and
resistance-trained athletes. We used 2-deoxy-2-[18F]fluoro-D-glucose and positron
emission tomography combined with the euglycemic hyperinsulinemic clamp technique
to compare the ability of insulin to stimulate myocardial, skeletal muscle, and
whole body glucose uptake between weight lifters (n = 8), endurance athletes (n =
8), and sedentary men (n = 9). Maximal aerobic power (ml. kg- 1. min- 1) was
higher in the endurance athletes (71 +/- 2, P < 0.001) than the weight lifters
(42 +/- 2) and the sedentary men (42 +/- 2). Skeletal muscle glucose uptake
(micromol. kg muscle- 1. min- 1) was enhanced in the endurance athletes (125 +/-
16, P < 0.01) but was similar in weight lifters (59 +/- 12) and sedentary (63 +/-
7) men. The rate of glucose uptake per unit mass of myocardium (micromol. kg- 1.
min- 1) was similarly decreased in endurance athletes (544 +/- 50) and weight
lifters (651 +/- 45) compared with sedentary men (1,041 +/- 78, P < 0.001 vs.
endurance athletes and weight lifters). Both groups of athletes had increased
left ventricular mass. Consequently, total left ventricular glucose uptake was
comparable in all groups. These data demonstrate that aerobic but not resistance
training is associated with enhanced insulin sensitivity in skeletal muscle.
Despite this, cardiac changes are remarkably similar in weight lifters and
endurance athletes and are characterized by an increase in left ventricular mass
and diminished insulin-stimulated glucose uptake per heart mass.
PMID- 10198308
TI - Insulin but not growth hormone stimulates protein anabolism in skin wound and
muscle.
AB - We have measured protein kinetics in the scalded skin and normal muscle in
anesthetized rabbits. On the 7th day after ear scald, L-[ring-13C6]phenylalanine
was infused as a tracer, and the ear and hindlimb were used as arteriovenous
units to reflect skin and muscle protein kinetics. Insulin was infused at 0.6 or
2.3-3.4 mU. kg-1. min-1 in the low-dose and high-dose insulin groups. In the
growth hormone group, recombinant human growth hormone was administered at 2 mg.
kg-1. day-1 after the ear was scalded. The results were compared with a control
group in which the ear was scalded but otherwise was not treated. In the control
group, net protein loss in the scalded skin and muscle was 23.1 +/- 21.4 and 3.9
+/- 1.5 micromol. 100 g-1. h-1, respectively. Insulin infusion at either high or
low dose reduced net protein loss to near zero by inhibiting proteolysis. In
contrast, growth hormone treatment had no anabolic effect on either tissue. In
conclusion, insulin but not growth hormone has an anabolic effect on scalded skin
and normal muscle; low-dose insulin is as effective in achieving an anabolic
effect on both tissues, with less hypoglycemic response than high-dose insulin.
PMID- 10198309
TI - Regulation of protein synthesis after acute resistance exercise in diabetic rats.
AB - These studies determined whether insulin-like growth factor-I (IGF-I) involvement
in exercise-stimulated anabolic processes becomes more evident during
hypoinsulinemia. Male Sprague-Dawley rats (n = 6-12/group) were made diabetic
(blood glucose congruent with 300 mg/dl) by partial pancreatectomy (PPX) or
remained nondiabetic (glucose congruent with 144 mg/dl). Rats performed acute
resistance exercise by repetitive standing on the hindlimbs with weighted
backpacks (ex), or they remained sedentary (sed). Resistance exercise caused
increases in rates of protein synthesis (nmol Phe incorporated. g muscle-1. h-1,
measured for gastrocnemius muscle in vivo 16 h after exercise) for both
nondiabetic [sed = 154 +/- 6 (SE) vs. ex = 189 +/- 7] and diabetic rats (PPXsed =
152 +/- 11 vs. PPXex = 202 +/- 14, P < 0.05). Arterial plasma insulin
concentrations in diabetic rats, congruent with180 pM, were less than one-half
those found in nondiabetic rats, congruent with444 pM, (P < 0.05). The activity
of eukaryotic initiation factor 2B (eIF2B; pmol GDP exchanged/min) was higher (P
< 0.05) in ex rats (sed = 0.028 +/- 0.006 vs. ex = 0.053 +/- 0.015; PPXsed =
0.033 +/- 0.013 vs. PPXex = 0.047 +/- 0.009) regardless of diabetic status.
Plasma IGF-I concentrations were higher in ex compared with sed diabetic rats (P
< 0.05). In contrast, plasma IGF-I was not different in nondiabetic ex or sed
rats. Muscle IGF-I (ng/g wet wt) was similar in ex and sed nondiabetic rats, but
in diabetic rats was 2- to 3-fold higher in ex (P < 0.05) than in sed rats. In
conclusion, moderate hypoinsulinemia that is sufficient to alter glucose
homeostasis does not inhibit an increase in rates of protein synthesis after
acute moderate-intensity resistance exercise. This preserved response may be due
to a compensatory increase in muscle IGF-I content and a maintained ability to
activate eIF2B.
PMID- 10198310
TI - Effect of calorie restriction on in vivo glucose metabolism by individual tissues
in rats.
AB - We evaluated the effects of 8 mo of calorie restriction [CR: 60% of ad libitum
(AL) food intake] on glucose uptake by 14 tissues in unanesthetized, adult (12
mo) F344xBN rats. Glucose metabolism was assessed by the 2-[3H]deoxyglucose
tracer technique at 1500 or 2100. Despite an approximately 60% decline in
insulinemia with CR, plasma 2-[3H]deoxyglucose clearance for CR was greater than
for AL at both times. A small, CR-related decrease in glucose metabolic index
(R'g) occurred only at 1500 in the spleen and heart, and this decrease was
reversed at 2100. In some tissues (cerebellum, lung, kidney, soleus, and
diaphragm), R'g was unaffected by diet, regardless of time. In the other tissues
(brown fat, 3 white fat pads, epitrochlearis, plantaris, and gastrocnemius), R'g
was higher or tended to be higher for CR vs. AL at one or both times. These
findings indicate that 8 mo of CR did not cause a continuous reduction in in vivo
glucose uptake by any tissue studied, and, in several insulin-sensitive tissues,
glucose uptake was at times greater for CR vs. AL rats.
PMID- 10198311
TI - Glucose effectiveness is the major determinant of intravenous glucose tolerance
in the rat.
AB - To determine the importance of insulin for glucose disposal during an intravenous
glucose tolerance test in rats, experiments were performed in four cohorts of
conscious unrestrained rats fasted overnight. In cohorts 1-3, a bolus of tracer
([3-3H]glucose, 50 microCi) was given alone, with glucose (0.3 g/kg) to induce an
endogenous insulin response (approximately 1,100 pmol/l), or with exogenous
insulin to give physiological (1,700 pmol/l) or supraphysiological (12,000
pmol/l) plasma levels. Raising plasma insulin within the physiological range had
no effect (P > 0.05), but supraphysiological levels induced hypoglycemia (7.3 +/-
0.2 to 3.6 +/- 0.2 mmol/l) and increased [3H]glucose disappearance rate (P <
0.001). In cohort 4, a primed, continuous tracer infusion was started 120 min
before saline or glucose bolus injection. [3H]glucose levels fell 15-20%, and the
disappearance rate rose 36% (P < 0.05) after glucose injection. These results
indicate that in fasted rats a tracer bolus injection protocol is not
sufficiently sensitive to measure the physiological effect of insulin released in
response to a bolus of glucose because this effect of insulin is small. Glucose
itself is the predominant mediator of glucose disposal after a bolus of glucose
in the fasted rat.
PMID- 10198312
TI - Effect of intravenous glutamine on duodenal mucosa protein synthesis in healthy
growing dogs.
AB - To determine whether glutamine acutely stimulates protein synthesis in the
duodenal mucosa, five healthy growing dogs underwent endoscopic biopsies of
duodenal mucosa at the end of three 4-h primed, continuous intravenous infusions
of L-[1-13C]leucine on three separate days, while receiving intravenous infusion
of 1) saline, 2) L-glutamine (800 micromol. kg-1. h-1), and 3) isonitrogenous
amounts of glycine. The three infusions were performed after 24 h of fasting, a
week apart from each other and in a randomized order. Glutamine infusion induced
a doubling in plasma glutamine level, and glycine caused a >10-fold rise in
plasma glycine level. During intravenous infusions of [13C]leucine, the plasma
leucine labeling attained a plateau value between 3.22 and 3.68 mole % excess
(MPE) and [13C]ketoisocaproate ([13C]KIC) of 2.91-2. 84 MPE; there were no
significant differences between glutamine, glycine, and saline infusion days.
Plasma leucine appearance rate was 354 +/- 33 (SE), 414 +/- 28, and 351 +/- 35
micromol. kg-1. h-1 (not significant) during glycine, saline, and glutamine
infusion, respectively. The fractional synthetic rate (FSR) of duodenal mucosa
protein was calculated from the rise in protein-bound [13C]leucine enrichment in
the biopsy sample, divided by time and with either plasma [13C]KIC or tissue free
[13C]leucine as precursor pool enrichment. Regardless of the precursor pool used
in calculations, duodenal protein FSR failed to rise significantly during
glutamine infusion (65 +/- 11%/day) compared either with saline (84 +/- 18%/day)
or glycine infusion days (80 +/- 15%/day). We conclude that 1) plasma [13C]KIC
and tissue free [13C]leucine can be used interchangeably as precursor pools to
calculate gut protein FSR; and 2) short intravenous infusion of glutamine does
not acutely stimulate duodenal protein synthesis in well-nourished, growing dogs.
PMID- 10198314
TI - The obese gene is expressed in lean littermates of the genetically obese mouse
(C57BL/6J ob/ob).
AB - Some individuals of the mixed group of "lean" littermates (+/ob and +/+) of
(C57BL/6J ob/ob) often suggest phenotypic characteristics of ob/ob animals.
Therefore, it was of interest to determine whether expression of the ob gene had
physiological significance in +/ob animals. Body weight (BW), fasting blood
glucose (FBG), and body core temperature (Tr) were monitored between 62 and 364
days of age in +/+ and +/ob mice. Among females but not males, +/ob mice were
heavier (P = 0.003) and FBG levels were greater (P = 0.04) than in +/+ animals.
Comparison of Tr indicated differences suggesting falling Tr in +/ob but rising
Tr in +/+ mice with age in males but not females. Multivariate analysis of
variance yielded genotype effects for both males (P = 0.002) and females (P =
0.02). BW, FBG, and Tr alone were sufficient at the 75% level for genotypic
characterization and separation of +/? animals as +/ob or +/+; clearly,
expression of the ob gene in heterozygotes of the +/ob animal may make the mixed
+/? group inappropriate as lean controls.
PMID- 10198313
TI - Surgery-induced insulin resistance in human patients: relation to glucose
transport and utilization.
AB - To investigate the underlying molecular mechanisms for surgery-induced insulin
resistance in skeletal muscle, six otherwise healthy patients undergoing total
hip replacement were studied before, during, and after surgery. Patients were
studied under basal conditions and during physiological hyperinsulinemia (60
microU/ml). Biopsies of vastus lateralis muscle were used to measure GLUT-4
translocation, glucose transport, and glycogen synthase activities. Surgery
reduced insulin-stimulated glucose disposal (P < 0.05) without altering the
insulin-stimulated increase in glucose oxidation or suppression of endogenous
glucose production. Preoperatively, insulin infusion increased plasma membrane
GLUT-4 in all six subjects (P < 0.05), whereas insulin-stimulated GLUT-4
translocation only occurred in three patients postoperatively (not significant).
Moreover, nonoxidative glucose disposal rates and basal levels of glycogen
synthase activities in muscle were reduced postoperatively (P < 0.05). These
findings demonstrate that peripheral insulin resistance develops immediately
postoperatively and that this condition might be associated with perturbations in
insulin-stimulated GLUT-4 translocation as well as nonoxidative glucose disposal,
presumably at the level of glycogen synthesis.
PMID- 10198315
TI - Effect of long-term caloric restriction and exercise on muscle bioenergetics and
force development in rats.
AB - We evaluated the hypothesis that long-term caloric restriction and exercise would
have beneficial effects on muscle bioenergetics and performance in the rat. By
themselves, each of these interventions is known to increase longevity, and
bioenergetic improvements are thought to be important in this phenomenon.
Accordingly, we investigated rats that underwent long-term caloric restriction
and were sedentary, ad libitum-fed rats permitted to exercise by daily
spontaneous wheel running (AE), and the combination of the dietary and exercise
interventions (RE). Ad libitum-fed, sedentary rats comprised the control group.
31P NMR spectra of the gastrocnemius muscle (GM) were collected in vivo at rest
and during two periods of electrical stimulation. Neither caloric restriction nor
exercise affected the ratio of phosphocreatine to ATP or pH at rest. During the
first stimulation and after recovery, the RE group had a significantly smaller
decline in pH than did the other groups (P < 0.05). During the second period of
stimulation, the decrease in pH was much smaller in all groups than during the
first stimulation, with no differences observed among the groups. The combination
of caloric restriction and exercise resulted in a significant attenuation in the
decline in developed force during the second period of stimulation (P < 0.05). A
biochemical correlate of this was a significantly higher concentration of citrate
synthase in the GM samples from the RE rats (32.7 +/- 5.4 micromol. min-1. g-1)
compared with the AE rats (17.6 +/- 5.7 micromol. min-1. g-1; P < 0.05). Our
experiments thus demonstrated a synergistic effect of long-term caloric
restriction and free exercise on muscle bioenergetics during electrical
stimulation.
PMID- 10198316
TI - Thyroid hormones modulate zinc transport activity of rat intestinal and renal
brush-border membrane.
AB - Thyroid hormone status influences the Zn2+ and metallothionein levels in
intestine, liver, and kidney. To evaluate the impact of thyroid hormones on Zn2+
metabolism, Zn2+ uptake studies were carried out in intestinal and renal brush
border membrane vesicles (BBMV). Steady-state Zn2+ transport in intestinal and
renal cortical BBMV was increased in hyperthyroid (Hyper-T) rats and decreased in
the hypothyroid (Hypo-T) rats relative to euthyroid (Eu-T) rats. In both the
intestinal and renal BBMV, Hyper-T rats showed a significant increase in maximal
velocity compared with Eu-T and Hypo-T rats. Apparent Michaelis constant was
unaltered in intestinal and renal BBMV prepared from the three groups.
Fluorescence anisotropy of diphenyl hexatriene was decreased significantly in
intestinal and renal brush-border membrane (BBM) isolated from Hyper-T rats
compared with Hypo-T and Eu-T rats. A significant reduction in the microviscosity
and transition temperature for Zn2+ uptake in intestinal and renal BBM from Hyper
T rats is in accordance with the increased fluidity of these BBMs. These findings
suggest that the increased rate of Zn2+ transport in response to thyroid hormone
status could be associated with either an increase in the number of Zn2+
transporters or an increase in the active transporters due to alteration in the
membrane fluidity. Thus the thyroid hormone-mediated change in membrane fluidity
might play an important role in modulating Zn2+ transport activity of intestinal
and renal BBM.
PMID- 10198317
TI - Platelet-activating factor may act as an endogenous pulse generator for sheep of
luteolytic PGF2alpha release.
AB - Pulsatile release of uterine prostaglandin F2alpha (PGF2alpha) induces luteolysis
in ruminants. However, the mechanism(s) that initiates and maintains luteolysis
has not been defined. The present study tested the hypothesis that the endogenous
PGF2alpha pulse generator is uterine-derived platelet-activating factor (PAF).
Ovariectomized ewes were given exogenous progesterone (P), estradiol (E), or both
(P+E, mimicking the normal luteal phase). Only ewes treated with steroids
released PAF into the uterine lumen and had increased PAF:acetylhydrolase
activity in the uterine lumen. Steroid treatment also influenced the capacity of
the uterus to release PGF2alpha in response to exogenous PAF. PAF infusion did
not affect plasma PGF2alpha metabolite (PGFM) levels in control (no steroid
treatment) ewes but increased plasma PGFM levels in P+E ewes (P < 0.001) and ewes
treated with P or E alone (P < 0.05). Infusion of PAF followed by or coincident
with oxytocin (OT) acted in a synergistic manner to increase plasma PGFM levels.
Repeated infusion of PAF into the uterus at 1-h intervals induced tachyphylaxis
of the PGFM response to PAF; however, sensitivity of the uterus to PAF returned
spontaneously by the 6th h. Interferon-tau (IFN-tau) inhibits pulsatile release
of PGF2alpha during pregnancy to prevent luteolysis. Exogenous recombinant ovine
IFN-tau (50 microgram) inhibited the uterine response to PAF alone or the
combined effects of PAF and OT. These results indicate that uterine PAF fulfills
many of the criteria for an endogenous PGF2alpha pulse-generator: steroid
induction of PAF production and uterine responsiveness to PAF-induced release of
PGF; synergistic stimulation of PAF-induced PGF release by OT; inhibition of PAF
effects by IFN-tau; and PAF's ability to induce pulses of PGF with a periodicity
during a period of chronic exposure of the uterus to PAF.
PMID- 10198318
TI - Expression of 25(OH)D3 24-hydroxylase in distal nephron: coordinate regulation by
1,25(OH)2D3 and cAMP or PTH.
AB - Previous studies using microdissected nephron segments reported that the
exclusive site of renal 25-hydroxyvitamin D3-24-hydroxylase (24OHase) activity is
the renal proximal convoluted tubule (PCT). We now report the presence of 24OHase
mRNA, protein, and activity in cells that are devoid of markers of proximal
tubules but express characteristics highly specific for the distal tubule.
24OHase mRNA was undetectable in vehicle-treated mouse distal convoluted tubule
(DCT) cells but was markedly induced when DCT cells were treated with 1,25
dihydroxyvitamin D3 [1,25(OH)2D3]. 24OHase protein and activity were also
identified in DCT cells by Western blot analysis and HPLC, respectively. 8-Bromo
cAMP (1 mM) or parathyroid hormone [PTH-(1-34); 10 nM] was found to potentiate
the effect of 1, 25(OH)2D3 on 24OHase mRNA. The stimulatory effect of cAMP or PTH
on 24OHase expression in DCT cells suggests differential regulation of 24OHase
expression in the PCT and DCT. In the presence of cAMP and 1, 25(OH)2D3, a four-
to sixfold induction in vitamin D receptor (VDR) mRNA was observed. VDR protein,
as determined by Western blot analysis, was also enhanced in the presence of
cAMP. Transient transfection analysis in DCT cells with rat 24OHase promoter
deletion constructs demonstrated that cAMP enhanced 1, 25(OH)2D3-induced 24OHase
transcription but this enhancement was not mediated by cAMP response elements
(CREs) in the 24OHase promoter. We conclude that 1) although the PCT is the major
site of localization of 24OHase, 24OHase mRNA and activity can also be localized
in the distal nephron; 2) both PTH and cAMP modulate the induction of 24OHase
expression by 1,25(OH)2D3 in DCT cells in a manner different from that reported
in the PCT; and 3) in DCT cells, upregulation of VDR levels by cAMP, and not an
effect on CREs in the 24OHase promoter, is one mechanism involved in the cAMP
mediated modulation of 24OHase transcription.
PMID- 10198319
TI - Effect of a selective rise in hepatic artery insulin on hepatic glucose
production in the conscious dog.
AB - In the present study we compared the hepatic effects of a selective increase in
hepatic sinusoidal insulin brought about by insulin infusion into the hepatic
artery with those resulting from insulin infusion into the portal vein. A
pancreatic clamp was used to control the endocrine pancreas in conscious
overnight-fasted dogs. In the control period, insulin was infused via peripheral
vein and the portal vein. After the 40-min basal period, there was a 180-min test
period during which the peripheral insulin infusion was stopped and an additional
1.2 pmol. kg-1. min-1 of insulin was infused into the hepatic artery (HART, n =
5) or the portal vein (PORT, n = 5, data published previously). In the HART
group, the calculated hepatic sinusoidal insulin level increased from 99 +/- 20
(basal) to 165 +/- 21 pmol/l (last 30 min). The calculated hepatic artery insulin
concentration rose from 50 +/- 8 (basal) to 289 +/- 19 pmol/l (last 30 min).
However, the overall arterial (50 +/- 8 pmol/l) and portal vein insulin levels
(118 +/- 24 pmol/l) did not change over the course of the experiment. In the PORT
group, the calculated hepatic sinusoidal insulin level increased from 94 +/- 30
(basal) to 156 +/- 33 pmol/l (last 30 min). The portal insulin rose from 108 +/-
42 (basal) to 192 +/- 42 pmol/l (last 30 min), whereas the overall arterial
insulin (54 +/- 6 pmol/l) was unaltered during the study. In both groups hepatic
sinusoidal glucagon levels remained unchanged, and euglycemia was maintained by
peripheral glucose infusion. In the HART group, net hepatic glucose output (NHGO)
was suppressed from 9.6 +/- 2.1 micromol. kg-1. min-1 (basal) to 4.6 +/- 1.0
micromol. kg-1. min-1 (15 min) and eventually fell to 3.5 +/- 0.8 micromol. kg-1.
min-1 (last 30 min, P < 0.05). In the PORT group, NHGO dropped quickly (P < 0.05)
from 10.0 +/- 0.9 (basal) to 7.8 +/- 1.6 (15 min) and eventually reached 3.1 +/-
1.1 micromol. kg-1. min-1 (last 30 min). Thus NHGO decreases in response to a
selective increase in hepatic sinusoidal insulin, regardless of whether it comes
about because of hyperinsulinemia in the hepatic artery or portal vein.
PMID- 10198320
TI - Nitric Oxide. III. A molecular prelude to intestinal inflammation.
AB - Nitric oxide (NO) synthesis is markedly augmented in states of inflammation,
largely due to the expression of inducible nitric oxide synthase (iNOS). Although
NO has anti-inflammatory consequences under basal conditions, it remains
enigmatic as to why NO displays proinflammatory characteristics in chronic
inflammation. Either the anti-inflammatory actions are weak and of little
consequence or, alternatively, other factors influence the role of NO in chronic
inflammation. We propose that the answer to this enigma lies in the conversion of
NO to other higher oxides of nitrogen (NO2, nitrogen dioxide; N2O3, dinitrogen
trioxide; and ONOO-, peroxynitrite). Emerging therapeutic strategies may be
independent of NO synthesis; e.g., antioxidants have no direct interaction with
NO but attenuate the levels and activity of higher nitrogen oxides. Thus, whereas
iNOS may be a marker for the proinflammatory actions of NO, the species that
mediate tissue injury/dysfunction in inflammation are likely to be nitrogen
oxides other than NO.
PMID- 10198321
TI - A novel Sp1-related cis element involved in intestinal alkaline phosphatase gene
transcription.
AB - We have used sodium butyrate-treated HT-29 cells as an in vitro model system to
study the molecular mechanisms underlying intestinal alkaline phosphatase (IAP)
gene activation. Transient transfection assays using human IAP-CAT reporter genes
along with DNase I footprinting were used to localize a critical cis element (IF
III) corresponding to the sequence 5'-GACTGGGCGGGGTCAAGATGGA-3'. Deletion of the
IF-III element resulted in a dramatic reduction in reporter gene activity, and IF
III was shown to function in the context of a heterologous (SV40) promoter in a
cell type-specific manner, further supporting its functional role in IAP
transactivation. Electrophoretic mobility shift assays revealed that IF-III binds
Sp1 and Sp3, but these factors comprise only a portion of the total nuclear
binding and appear to mediate only a small portion of its transcriptional
activity. IF-III does not correspond to any previously characterized regulatory
region from other intestine-specific genes. We have thus identified a novel, Sp1
related cis-regulatory element in the human IAP gene that appears to play a role
in its transcriptional activation during differentiation in vitro.
PMID- 10198322
TI - COOH-terminally extended secretins are potent stimulants of pancreatic secretion.
AB - Posttranslational processing of preprosecretin generates several COOH-terminally
extended forms of secretin and alpha-carboxyl amidated secretin. We used
synthetic canine secretin analogs with COOH-terminal -amide, -Gly, or -Gly-Lys
Arg to examine the effects of COOH-terminal extensions of secretin on bioactivity
and detection in RIA. Synthetic products were purified by reverse-phase and ion
exchange HPLC and characterized by reverse-phase isocratic HPLC and amino acid,
sequence, and mass spectral analyses. Secretin and secretin-Gly were noted to
coelute during reverse-phase HPLC. In RIA using eight different antisera raised
against amidated secretin, COOH-terminally extended secretins had little or no
cross-reactivity. Bioactivity was assessed by measuring pancreatic responses in
anesthetized rats. Amidated canine and porcine secretins were equipotent.
Secretin-Gly and secretin-Gly-Lys-Arg had potencies of 81 +/- 9% (P > 0.05) and
176 +/- 13% (P < 0.01), respectively, compared with amidated secretin, and the
response to secretin-Gly-Lys-Arg lasted significantly longer. These data
demonstrate that 1) amidated secretin and secretin-Gly are not separable under
some chromatographic conditions, 2) current RIA may not detect bioactive COOH
terminally extended forms of secretin in tissue extracts or blood, and 3) the
secretin receptor mediating stimulation of pancreatic secretion recognizes both
amidated and COOH-terminally extended secretins.
PMID- 10198323
TI - Autocrine and paracrine actions of intestinal fibroblast-derived insulin-like
growth factors.
AB - Paracrine and autocrine actions of the insulin-like growth factors (IGFs) are
inferred by local expression within the bowel. CCD-18Co cells, IEC-6 cells, and
immunoneutralization were used to analyze whether IGFs have direct autocrine or
paracrine effects on proliferation of cultured intestinal fibroblasts and
epithelial cells. Growth factor expression was analyzed by ribonuclease
protection assay and RT-PCR. Extracellular matrix (ECM) was analyzed for effects
on cell proliferation. CCD-18Co cells express IGF-II mRNAs and low levels of IGF
I mRNA. Conditioned medium from CCD-18Co cells (CCD-CM) stimulated proliferation
of IEC-6 and CCD-18Co cells. Neutralization of IGF immunoreactivity in CCD-CM
reduced but did not abolish this effect. RT-PCR and immunoneutralization
demonstrated that other growth factors contribute to mitogenic activity of CCD
CM. Preincubation of CCD-CM with ECM prepared from IEC-6 or CCD-18Co cells
reduced its mitogenic activity. ECM from CCD-18Co cells enhanced growth factor
dependent proliferation of IEC-6 cells. IEC-6 cell ECM inhibited IGF-I action on
CCD-18Co cells. We conclude that IGF-II is a potent autocrine mitogen for
intestinal fibroblasts. IGF-II interacts with other fibroblast-derived growth
factors and ECM to stimulate proliferation of intestinal epithelial cells in a
paracrine manner.
PMID- 10198324
TI - Assessment of the mechanism of juxtacrine activation and adhesion of leukocytes
in liver microcirculation.
AB - Leukotriene C4 (LTC4), histamine, and other mediators can induce expression of P
selectin and platelet-activating factor (PAF) on venular endothelium to recruit
leukocytes in vivo and in vitro via a juxtacrine mechanism of adhesion. The
objective of this study was to assess the effect of histamine and LTC4 on the
leukocyte recruitment in the liver and to study the components and molecular
mechanisms involved in this process. We visualized the hepatic microvasculature
using intravital microscopy and we determined that LTC4 (20 nM) but not histamine
(0.1, 0.3, or 1 mM) induced leukocyte recruitment in the liver microcirculation.
Histamine could induce leukocyte recruitment but only in the presence of an
antihistaminase. The LTC4-induced leukocyte recruitment occurred primarily in
sinusoids (not venules) and was not inhibitable by three different anti-P
selectin antibodies (5H1, RMP-1, and RB40). Leukocyte recruitment in P-selectin
deficient mice, intercellular adhesion molecule 1 (ICAM-1)-deficient mice, and
mice treated with a PAF antagonist was of the same magnitude as in wild-type
animals in response to LTC4. Although PAF alone could induce adhesion in both
sinusoids and postsinusoidal venules, this chemotactic agent was not involved in
LTC4-induced adhesion in the liver. Finally, an overlapping role for P-selectin
and ICAM-1 was ruled out as LTC4 induced leukocyte recruitment in P-selectin and
ICAM-1 double-deficient mice. These data demonstrate that LTC4 does not activate
the known early mechanisms of leukocyte recruitment, including P-selectin, PAF,
or ICAM-1 in the hepatic microvasculature.
PMID- 10198325
TI - Secretagogue-induced digestive enzyme activation and cell injury in rat
pancreatic acini.
AB - The mechanisms responsible for intrapancreatic digestive enzyme activation as
well as the relationship between that activation and cell injury during
pancreatitis are not understood. We have employed an in vitro system in which
freshly prepared pancreatic acini are exposed to a supramaximally stimulating
concentration of the CCK analog caerulein to explore these issues. We find that
in vitro trypsinogen activation depends on the continued presence of Ca2+ in the
suspending medium and that it is half-maximal in the presence of 0.3 mM Ca2+.
Caerulein-induced trypsinogen activation can be halted by removal of Ca2+ from
the suspending medium or by chelation of intracellular Ca2+. Increasing
intracellular Ca2+ with either ionomycin or thapsigargin does not induce
trypsinogen activation. We have monitored cell injury by measuring the leakage of
lactate dehydrogenase (LDH) from acini and by quantitating intercalation of
propidium iodide (PI) into DNA. Leakage of LDH and intercalation of PI in
response to supramaximal stimulation with caerulein can be detected only after
caerulein-induced trypsinogen activation has already occurred, and these
indications of cell injury can be prevented by addition of a cell-permeant
protease inhibitor. Our findings indicate that caerulein-induced intra-acinar
cell activation of trypsinogen depends on a rise in intracellular Ca2+, which
reflects entry of Ca2+ from the suspending medium. Intra-acinar cell activation
of trypsinogen is an early as well as a critical event in pancreatitis. The
subsequent cell injury in this model is mediated by activated proteases.
PMID- 10198326
TI - Characterization and regulation of Ca2+-dependent K+ channels in human esophageal
smooth muscle.
AB - We examined the properties of K+ channels in smooth muscle cells dissociated from
human esophagus using patch-clamp recording in the cell-attached configuration.
The predominant channel observed had a conductance of 224 +/- 4 pS, and current
reversal was dependent on K+ concentration. Channel activity was voltage
dependent and increased with elevation of intracellular free Ca2+ concentration
([Ca2+]i), consistent with this being the large-conductance Ca2+-dependent K+
(KCa) channel. ACh as well as caffeine caused transient increases in KCa channel
activity, and the effects of ACh persisted in Ca2+-free solution, indicating that
Ca2+ release from stores contributed to channel activation. Simultaneous patch
clamp and fluorescence revealed that KCa channel activity was well correlated
with elevation of [Ca2+]i. The functional role of KCa channels in esophagus was
studied by measuring ACh-induced contraction of strips of muscle.
Tetraethylammonium and iberiotoxin, blockers of KCa channels, increased ACh
induced contraction, consistent with a role for K+ channels in limiting
excitation and contraction. These studies are the first to characterize KCa
channels and their regulation in human esophageal smooth muscle.
PMID- 10198327
TI - Differential activation of phosphoinositide 3-kinase by endothelin and ceramide
in colonic smooth muscle cells.
AB - We have investigated the hypothesis that different contractile agonists activate
distinct catalytic subunits of phosphoinositide (PI) 3-kinase in smooth muscle
cells. Endothelin (10(-7) M) induced a sustained increase in PI 3-kinase activity
at both 30 s and 4 min of stimulation (151.5 +/- 8.5% at 30 s and 175.8 +/- 8.7%
at 4 min, P < 0.005). Preincubation of smooth muscle cells with the tyrosine
kinase inhibitor genistein (3 microM) resulted in a significant inhibition of
both C2 ceramide-induced and endothelin-induced PI 3-kinase activation and
contraction. Preincubation with herbimycin A, an Src kinase inhibitor (3 microM),
inhibited only C2 ceramide-induced PI 3-kinase activation and contraction.
Western blotting using Src kinase antibody showed that C2 ceramide, not
endothelin, stimulated the phosphorylation of Src kinase. Western blotting and
immunoprecipitation with PI 3-kinase antibodies to the regulatory subunit p85 and
the catalytic subunits p110alpha and p110gamma indicated that both endothelin and
C2 ceramide interacted with the regulatory subunit p85; endothelin interacted
with the catalytic subunits p110alpha and p110gamma, whereas C2 ceramide
interacted only with the catalytic subunit p110alpha. In summary, C2 ceramide
activated PI 3-kinase p110alpha subunit by a tyrosine kinase-mediated pathway,
whereas endothelin-induced contraction, unlike C2 ceramide, was not mediated by
the activation of Src kinase but was mediated by G protein activation of both
p110alpha and p110gamma subunits (type IA and IB) of PI 3-kinase.
PMID- 10198328
TI - Cholinergic and GABAergic regulation of nitric oxide synthesis in the guinea pig
ileum.
AB - Nitric oxide (NO) synthesis was examined in intact longitudinal muscle-myenteric
plexus preparations of the guinea pig ileum by determining the formation of
[3H]citrulline during incubation with [3H]arginine. Spontaneous [3H]citrulline
production after 30 min was 80-90 dpm/mg, which constituted approximately 1% of
the tissue radioactivity. Electrical stimulation (10 Hz) led to a threefold
increase in [3H]citrulline formation. Removal of calcium from the medium or
addition of NG-nitro-L-arginine strongly inhibited both spontaneous and
electrically induced production of [3H]citrulline. TTX reduced the electrically
induced but not spontaneous [3H]citrulline formation. The electrically induced
formation of [3H]citrulline was diminished by (+)-tubocurarine and mecamylamine
and enhanced by scopolamine, which suggests that endogenous ACh inhibits, via
muscarinic receptors, and stimulates, via nicotinic receptors, the NO synthesis
in the myenteric plexus. The GABAA receptor agonist muscimol and GABA also
reduced the electrically evoked formation of [3H]citrulline, whereas baclofen was
without effect. Bicuculline antagonized the inhibitory effect of GABA. It is
concluded that nitrergic myenteric neurons are equipped with GABAA receptors,
which mediate inhibition of NO synthesis.
PMID- 10198329
TI - Peripheral urocortin delays gastric emptying: role of CRF receptor 2.
AB - Urocortin, a new mammalian member of the corticotropin-releasing factor (CRF)
family has been proposed to be the endogenous ligand for CRF receptor 2 (CRF-R2).
We studied the influence of intravenous urocortin on gastric emptying and the
role of CRF-R2 in peptide action and postoperative gastric ileus in conscious
rats. The intravenous doses of rat CRF and rat urocortin producing 50% inhibition
of gastric emptying were 2.5 and 1.1 microgram/kg, respectively. At these
intravenous doses, CRF and urocortin have their actions fully reversed by the CRF
R1/CRF-R2 antagonist astressin at antagonist/agonist ratios of 5:1 and 67:1,
respectively. Astressin (12 microgram/kg iv) completely prevented abdominal
surgery-induced 54% inhibition of gastric emptying 3 h after surgery while having
no effect on basal gastric emptying. The selective nonpeptide CRF-R1 antagonists
antalarmin (20 mg/kg ip) and NBI-27914 (400 microgram/kg iv) did not influence
intravenous CRF-, urocortin- or surgery-induced gastric stasis. These results as
well as earlier ones showing that alpha-helical CRF9-41 (a CRF-R2 more selective
antagonist) partly prevented postoperative ileus indicate that peripheral CRF-R2
may be primarily involved in intravenous urocortin-, CRF-, and abdominal surgery
induced gastric stasis.
PMID- 10198330
TI - Endogenous interstitial adenosine in isolated myenteric neural networks varies
inversely with prevailing PO2.
AB - Isolated myenteric ganglion networks were used in a perifusion protocol to
characterize the response of interstitial adenosine levels to changes in
prevailing PO2. The biological activity of such adenosine was assessed using
inhibition of release of substance P (SP) as a functional measure of adenosine
activity, and the effect of altered O2 tension on both spontaneous and elevated
extracellular K+ concentration-evoked SP release from networks was determined
over a range of PO2 values from hypoxic (PO2 = 54 mmHg) to hyperoxic (PO2 = 566
mmHg). Release of SP was found to be sensitive to PO2, and a linear graded
relationship was obtained. Perifusion in the additional presence of the adenosine
A1-receptor-selective antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX)
revealed considerable adenosinergic inhibition with an inverse exponential
relationship and hyperoxic threshold PO2. Disinhibition of evoked SP release by
DPCPX in the absence of TTX was double that observed in its presence, indicating
a neural source for some of the adenosine released during hypoxia. A postulated
neuroprotective role for adenosine is consistent with the demonstrated
relationship between interstitial adenosine and prevailing O2 tension.
PMID- 10198331
TI - Validation of a novel luminal flow velocimeter with video fluoroscopy and
manometry in the human esophagus.
AB - There is currently no ideal method for concurrently assessing intraluminal
pressures and flows in humans with high temporal resolution. We have developed
and assessed the performance of a novel fiber-optic laser-Doppler velocimeter,
mounted in a multichannel manometric assembly. Velocimeter recordings were
compared with concurrent fluoroscopy and manometry following 50 barium swallows
in healthy subjects. During these swallows, the velocimeter sensor was situated
in either the proximal (24 swallows) or the distal (26 swallows) esophagus. It
signaled intraluminal flow following 46 of 50 swallows. A greater mean number of
deflections were recorded in the distal compared with the proximal esophagus (4.
3 vs. 2.4, P = 0.001). The maximal flow velocity recorded did not differ between
the proximal and distal esophagus (76.7 vs. 73.8 mm/s). No velocimeter signals
commenced after fluoroscopic lumen occlusion. The velocimeter signals were
closely temporally related to fluoroscopic barium flow. Upward catheter movement
on swallowing sometimes appeared to cause a velocimeter signal. Manometrically
"normal" swallows were no different from "abnormal" swallows in the number and
velocity of deflections recorded by the velocimeter. This novel instrument
measures intraluminal flow velocity and pressures concurrently, thus enabling
direct study of pressure-flow relationships. Flow patterns differed between the
proximal and distal esophagus.
PMID- 10198332
TI - Downregulation of Galphaq-11 protein expression in guinea pig antral and colonic
circular muscle during pregnancy.
AB - Pregnancy has an inhibitory effect on motility of the gastrointestinal tract. The
present study was designed to examine the mechanisms responsible for antral and
colonic hypomotility in pregnant guinea pigs. Circular smooth muscle cells from
the antrum and left colon were isolated by enzymatic digestion with collagenase
from pregnant and nonpregnant guinea pigs. Contractile responses to agonists were
expressed as percent shortening from resting cell length. The function of G
proteins in antral and colonic circular smooth muscle was assessed by
[35S]guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) binding induced by CCK-8 and
G protein quantitation. The contraction of antral and colonic circular smooth
muscle from pregnant guinea pigs was reduced in response to CCK-8 and to
GTPgammaS but was normal in response to KCl and D-myo-inositol 1,4,5
trisphosphate compared with nonpregnant animals. The stimulation of
[35S]GTPgammaS binding to Galphaq-11 induced by 1 microM CCK-8 was significantly
lower in antral and colonic circular smooth muscle from pregnant guinea pigs than
that in controls. Furthermore, Western blot analysis showed a decreased Galphaq
11 and an increased Gsalpha protein content in both tissues during pregnancy. It
is concluded that pregnancy appears to impair gastrointestinal circular smooth
muscle contractility by downregulating G proteins such as Galphaq-11 protein,
which mediates muscle contraction, and upregulating Gsalpha protein, which
mediates muscle relaxation.
PMID- 10198333
TI - Intracisternal TRH analog increases gastrin release and corpus histidine
decarboxylase activity in rats.
AB - Thyrotropin-releasing hormone (TRH) acts in brain stem nuclei to induce vagally
mediated stimulation of gastric secretion. The effects of intracisternal
injection of the TRH analog RX-77368 on plasma gastrin levels and corpus
histidine decarboxylase (HDC) activity were studied in 48-h fasted conscious
rats. RX-77368 (25-100 ng) increased plasma gastrin levels by threefold at 30
min, which remained significantly higher than control at 2 and 4 h postinjection.
Corpus HDC activity began to increase at 2 h and reached a peak at 4 h
postinjection with a 21-fold maximum response observed at 50 ng. Morphological
changes in the appearance of corpus HDC-immunoreactive cells correlated well with
HDC activity. Pretreatment with gastrin monoclonal antibody completely prevented
RX-77368 stimulatory effects on HDC activity. Atropine significantly attenuated
gastrin increase at 30 min by 26%. These results indicated that in conscious
fasted rats, TRH analog acts in the brain to increase corpus HDC activity in the
enterochromaffin-like cells, which involves gastrin release stimulated by central
TRH analog.
PMID- 10198334
TI - Effects of IBMX on norepinephrine-induced vasoconstriction in small mesenteric
arteries.
AB - The present study assesses the effects of the phosphodiesterase inhibitor IBMX on
norepinephrine (NE)-induced constriction of small mesenteric arteries. Arteries (
approximately 150 micrometer) were dissected from rats and mounted on a wire
myograph for isometric force measurement. NE concentration effect curves were
generated after exposure to 500 microM IBMX for 60 min. IBMX significantly
reduced NE-induced tension development. Studies were also conducted following
sarcoplasmic reticulum (SR) depletion (ryanodine, 10 microM) or L-type Ca2+
channel blockade [(+)-BAY K 8644, 10 microM] in the presence and absence of IBMX.
Both SR depletion and L-channel blockade reduced NE-induced tension generation,
consistent with incomplete Ca2+ mobilization. IBMX significantly attenuated NE
responses in ryanodine and (+)-BAY K 8644-treated vessels. Finally, treatment of
NE-stimulated vessels with IBMX (500 microM) caused a reduction in vascular
tension that was greater than the concomitant reduction in cytosolic Ca2+
concentration ([Ca2+]i), indicating that a portion of the IBMX-mediated
relaxation is Ca2+-independent. These data suggest that IBMX attenuation of NE
responsiveness not only involves a reduction in [Ca2+]i but also a significant
decrease in Ca2+ sensitivity.
PMID- 10198335
TI - Involvement of RhoA and its interaction with protein kinase C and Src in CCK
stimulated pancreatic acini.
AB - We evaluated intracellular pathways responsible for the activation of the small
GTP-binding protein Rho p21 in rat pancreatic acini. Intact acini were incubated
with or without CCK and carbachol, and Triton X-100-soluble and crude microsomes
were used for Western immunoblotting. When a RhoA-specific antibody was used, a
single band at the location of 21 kDa was detected. CCK (10 pM-10 nM) and
carbachol (0.1-100 microM) dose dependently increased the amount of
immunodetectable RhoA with a peak increase occurring at 3 min. High-affinity CCK
A-receptor agonists JMV-180 and CCK-OPE (1-1,000 nM) did not increase the
intensities of the RhoA band, suggesting that stimulation of RhoA is mediated by
the low-affinity CCK-A receptor. Although an increase in RhoA did not require the
presence of extracellular Ca2+, the intracellular Ca2+ chelator 1, 2-bis(2
aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-AM abolished the appearance of the
RhoA band in response to CCK and carbachol. The Gq protein inhibitor G protein
antagonist-2A (10 microM) and the phospholipase C (PLC) inhibitor U-73122 (10
microM) markedly reduced RhoA bands in response to CCK. The protein kinase C
(PKC) activator phorbol ester (10-1,000 nM) dose dependently increased the
intensities of the RhoA band, which were inhibited by the PKC inhibitor K-252a (1
microM). The pp60(c-src) inhibitor herbimycin A (6 microM) inhibited the RhoA
band in response to CCK, whereas the calmodulin inhibitor W-7 (100 microM) and
the phosphoinositide 3-kinase inhibitor wortmannin (6 microM) had no effect. RhoA
was immunoprecipitated with Src, suggesting association of RhoA with Src.
Increases in mass of this complex were observed with CCK stimulation. In
permeabilized acini, the Rho inhibitor Clostridium botulinum C3 exoenzyme dose
dependently inhibited amylase secretion evoked by a Ca2+ concentration with an
IC50 of C3 exoenzyme at 1 ng/ml. We concluded that the small GTP-binding protein
RhoA p21 exists in pancreatic acini and appears to be involved in the mediation
of pancreatic enzyme secretion evoked by CCK and carbachol. RhoA pathways are
involved in the activation of PKC and Src cascades via Gq protein and PLC.
PMID- 10198336
TI - Intravenous glycine improves survival in rat liver transplantation.
AB - In situ manipulation by touching, retracting, and moving liver lobes gently
during harvest dramatically reduces survival after transplantation (P. Schemmer,
R. Schoonhoven, J. A. Swenberg, H. Bunzendahl, and R. G. Thurman. Transplantation
65: 1015-1020, 1998). The development of harvest-dependent graft injury upon
reperfusion can be prevented with GdCl3, a rare earth metal and Kupffer cell
toxicant, but it cannot be used in clinical liver transplantation because of its
potential toxicity. Thus the effect of glycine, which prevents activation of
Kupffer cells, was assessed here. Minimal dissection of the liver for 12 min plus
13 min without manipulation had no effect on survival (100%). However, gentle
manipulation decreased survival to 46% in the control group. Furthermore, serum
transaminases and liver necrosis were elevated 4- to 12-fold 8 h after
transplantation. After organ harvest, the rate of entry and exit of fluorescein
dextran, a dye confined to the vascular space, was decreased about twofold,
indicating disturbances in the hepatic microcirculation. Pimonidazole binding,
which detects hypoxia, increased about twofold after organ manipulation, and
Kupffer cells isolated from manipulated livers produced threefold more tumor
necrosis factor-alpha after lipopolysaccharide than controls. Glycine given
intravenously to the donor increased the serum glycine concentration about
sevenfold and largely prevented the effect of gentle organ manipulation on all
parameters studied. These data indicate for the first time that pretreatment of
donors with intravenous glycine minimizes reperfusion injury due to organ
manipulation during harvest and after liver transplantation.
PMID- 10198337
TI - Microvascular perfusion deficits are not a prerequisite for mucosal injury in
septic rats.
AB - Our major objective was to investigate whether injury to the mucosa of the small
intestine occurred in a normotensive model of sepsis and whether such injury was
associated with microvascular perfusion deficits. Using fluorescence intravital
microscopy, we show direct evidence of cell injury within the mucosa (pneumonia
12.4 +/- 2.6 cells/field, sham 2.2 +/- 0.7 cells/field), whereas use of 51Cr
labeled EDTA showed evidence of increased mucosal permeability (pneumonia 1.90 +/
0.67 ml. min-1. 100 g-1; sham 0.24 +/- 0.04 ml. min-1. 100 g-1), 48 h following
induction of pneumonia. Despite such injury the capillary density in the ileal
mucosa and submucosa of pneumonic rats (1,027 +/- 77 and 1,717 +/- 86 mm2) was
not significantly different compared with sham (998 +/- 63 and 1,812 +/- 101
mm2). However, a modest albeit significant decrease in capillary perfusion was
measured in the muscularis layer of pneumonia (11.0 +/- 1.3 mm) compared with
sham (13.9 +/- 0.63 mm) and appeared to be associated with leukocyte entrapment.
Pretreatment using low doses of endotoxin to induce endotoxin tolerance not only
increased muscularis capillary density but reduced the number of leukocytes
trapped within the microvasculature, decreased myeloperoxidase activity within
the ileum in pneumonic rats, and prevented mucosal injury. In conclusion, we have
shown that pneumonia results in remote injury to the mucosa of the ileum and that
such injury was not associated with concurrent mucosal perfusion deficits.
PMID- 10198338
TI - Probiotics inhibit enteropathogenic E. coli adherence in vitro by inducing
intestinal mucin gene expression.
AB - Probiotic agents, live microorganisms with beneficial effects for the host, may
offer an alternative to conventional antimicrobials in the treatment and
prevention of enteric infections. The probiotic agents Lactobacillus plantarum
299v and Lactobacillus rhamnosus GG quantitatively inhibited the adherence of an
attaching and effacing pathogenic Escherichia coli to HT-29 intestinal epithelial
cells but did not inhibit adherence to nonintestinal HEp-2 cells. HT-29 cells
were grown under conditions that induced high levels of either MUC2 or MUC3 mRNA,
but HEp-2 cells expressed only minimal levels of MUC2 and no MUC3 mRNA. Media
enriched for MUC2 and MUC3 mucin were added exogenously to binding assays and
were shown to be capable of inhibiting enteropathogen adherence to HEp-2 cells.
Incubation of L. plantarum 299v with HT-29 cells increased MUC2 and MUC3 mRNA
expression levels. From these in vitro studies, we propose the hypothesis that
the ability of probiotic agents to inhibit adherence of attaching and effacing
organisms to intestinal epithelial cells is mediated through their ability to
increase expression of MUC2 and MUC3 intestinal mucins.
PMID- 10198339
TI - Increased gastrointestinal permeability is an early lesion in the spontaneously
diabetic BB rat.
AB - The BB rat spontaneously develops autoimmune diabetes. Feeding these animals a
hydrolyzed casein diet significantly reduces the incidence of this disease,
suggesting that a dietary antigen is involved in the pathogenesis of this
disease. In other syndromes associated with luminal antigens, including celiac
and Crohn's disease, increased intestinal permeability has been suggested to play
an etiological role. Therefore, the objective of this study was to evaluate
whether increased permeability was also present in BB rats before disease
development. By measuring gastrointestinal permeability, in animals on a regular
or hydrolyzed casein diet, we were able to demonstrate that increased gastric and
small intestinal permeability appeared before the development of both insulitis
and clinical diabetes. Although hydrolysis of dietary protein significantly
reduced the incidence of diabetes, it did not alter the small intestinal
permeability abnormality, suggesting that this is an early event. Increased
permeability appears to have an early role in the genesis of several
immunological diseases and may represent a common event in these diseases.
PMID- 10198340
TI - Specific 1,25(OH)2D3-mediated regulation of transcellular calcium transport in
Caco-2 cells.
AB - Calcium transport in the apical-to-basolateral (A-to-B) or B-to-A direction was
examined in cells treated with 10 nM 1, 25-dihydroxyvitamin D3 [1,25(OH)2D3,
calcitriol] for up to 72 h. Net A-to-B calcium transport was positive at all time
points and increased from 0.14 +/- 0.06 to 0.50 +/- 0.01 nmol. well-1. min-1
after 72 h of calcitriol treatment. Neither phenol red transport nor
transepithelial electrical resistance was altered by calcitriol treatment,
suggesting that the increase in net A-to-B calcium transport was not due to
paracellular movement. Neither 25-hydroxyvitamin D3 nor 24,25-dihydroxyvitamin D3
(100 nM, 48 h) alters basal or calcitriol-stimulated A-to-B calcium transport.
Treatment with the calmodulin antagonist trifluoperazine (50 microM) reduced
calcitriol-stimulated A-to-B Ca transport by 56%. The transcription inhibitor
actinomycin D inhibited calcitriol-regulated A-to-B calcium transport as well as
calbindin D9k and 24-hydroxylase mRNA accumulation. These data demonstrate that
calcitriol-mediated A-to-B calcium transport in Caco-2 cells is a specific,
transcellular process that requires transcriptional events normally mediated
through the vitamin D receptor.
PMID- 10198341
TI - Ethanol modulation of intestinal epithelial tight junction barrier.
AB - Previous studies have shown that high concentrations of ethanol (>/=40%) cause
functional damage of the gastrointestinal epithelial barrier by direct cytotoxic
effect on the epithelial cells. The effects of lower noncytotoxic doses of
ethanol on epithelial barrier function are unknown. A major function of
gastrointestinal epithelial cells is to provide a barrier against the hostile
substances in the gastrointestinal lumen. The apicolaterally located tight
junctions (TJs) form a paracellular seal between the lateral membranes of
adjacent cells and act as a paracellular barrier. In this study, we investigated
the effects of lower doses of ethanol on intestinal epithelial TJ barrier
function using filter-grown Caco-2 intestinal epithelial monolayers. The Caco-2
TJ barrier function was assessed by measuring epithelial resistance or
paracellular permeability of the filter-grown monolayers. Ethanol (0, 1, 2.5, 5,
7.5, and 10%) produced a dose-related drop in Caco-2 epithelial resistance and
increase in paracellular permeability. Ethanol also produced a progressive
disruption of TJ protein (ZO-1) with separation of ZO-1 proteins from the
cellular junctions and formation of large gaps between the adjacent cells.
Ethanol, at the doses used (=10%), did not cause cytotoxicity (lactate
dehydrogenase release) to the Caco-2 cells. Ethanol produced a disassembly and
displacement of perijunctional actin and myosin filaments from the perijunctional
areas. On ethanol removal, actin and myosin filaments rapidly reassembled at the
cellular borders. Ethanol stimulated the Caco-2 myosin light chain kinase (MLCK)
activity but did not affect the MLCK protein levels. Specific MLCK inhibitor ML-7
inhibited both ethanol increases in MLCK activity and TJ permeability without
affecting the MLCK protein levels. Consistent with these findings, metabolic
inhibitors sodium azide and 2,4-dinitrophenol significantly prevented ethanol
induced increase in Caco-2 TJ permeability, whereas cycloheximide or actinomycin
D had no effect. The results of this study indicate that ethanol at low
noncytotoxic doses causes a functional and structural opening of the Caco-2
intestinal epithelial TJ barrier by activating MLCK.
PMID- 10198342
TI - Induction of epithelial Na+ channel in rat ileum after proctocolectomy.
AB - In patients with colectomy, epithelial transport function in the remnant small
intestine can be regulated in response to the increased fecal electrolyte and
fluid loss. Using a rat colectomy model, we investigated the Na+ and K+ transport
mechanisms underlying the intestinal response. Proctocolectomy with ileoanal
anastomosis was performed on rats. The small intestinal mucosa was mounted in
Ussing chambers; then short-circuit currents and 22Na+ fluxes were measured. mRNA
expression of the epithelial Na+ channel (ENaC) was determined by Northern
blotting. Amiloride-sensitive, electrogenic Na+ absorption appeared in the ileum
after proctocolectomy. This functional change was accompanied by the
chronological induction of mRNAs for alpha-, beta-, and gamma-subunits of the
ENaC in the ileum. Tetraethylammonium-sensitive short-circuit current was also
activated. We conclude that electrogenic Na+ absorption and probably K+ secretion
are induced in the ileum after proctocolectomy. This induction of electrogenic
Na+ absorption is probably mediated by the increase in the mRNA levels for all
three types of subunits of the ENaC and may contribute to the recovery from the
increased fecal Na+ loss.
PMID- 10198343
TI - Excretion of progastrin products in human urine.
AB - The renal handling of carboxyamidated gastrins, NH2-terminal progastrin
fragments, and glycine-extended gastrins was examined in healthy volunteers. The
respective urinary clearances after a meal amounted to 0.09 +/- 0.02%, 0.17 +/-
0.04% (P < 0.05), and 0.04 +/- 0.01% (P < 0.01) of the glomerular filtration
rate. During intravenous infusion of carboxyamidated gastrin-17, progastrin
fragment-(1-35), and glycine-extended gastrin-17, the respective urinary
clearances amounted to 0.08 +/- 0.02, 0.46 +/- 0.08, and 0. 02 +/- 0.01%,
respectively, of the glomerular filtration rate. The metabolic clearance rate of
the three peptides was 24.4 +/- 1.3, 6.0 +/- 0.4, and 8.6 +/- 0.7 ml. kg-1. min
1. A maximum rate for tubular transport or degradation of the peptides could not
be determined, nor was a renal plasma threshold recorded. Plasma concentrations
and urinary excretion rates correlated for gastrin-17 and progastrin fragment-(1
35) (r = 0.94 and 0.97, P < 0.001), whereas the excretion of glycine-extended
gastrin diminished with increasing plasma concentrations. We conclude that renal
excretion of progastrin products is negligible compared with renal metabolism and
that renal handling of the peptides depends on their molecular structure. Hence,
the kidneys exhibited a higher excretion of NH2-terminal progastrin fragments
than of carboxyamidated and especially glycine-extended gastrins.
PMID- 10198344
TI - 1,25-dihydroxyvitamin D3 and TPA activate phospholipase D in Caco-2 cells: role
of PKC-alpha.
AB - 1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] and 12-O-tetradecanoylphorbol 13-acetate
(TPA) both activated phospholipase D (PLD) in Caco-2 cells. GF-109203x, an
inhibitor of protein kinase C (PKC) isoforms, inhibited this activation by both
of these agonists. 1,25(OH)2D3 activated PKC-alpha, but not PKC-beta1, -betaII,
delta, or -zeta, whereas TPA activated PKC-alpha, -beta1, and -delta. Chronic
treatment with TPA (1 microM, 24 h) significantly reduced the expression of PKC
alpha, -betaI, and -delta and markedly reduced the ability of 1,25(OH)2D3 or TPA
to acutely stimulate PLD. Removal of Ca2+ from the medium, as well as
preincubation of cells with Go-6976, an inhibitor of Ca2+-dependent PKC isoforms,
significantly reduced the stimulation of PLD by 1,25(OH)2D3 or TPA. Treatment
with 12-deoxyphorbol-13-phenylacetate-20-acetate, which specifically activates
PKC-betaI and -betaII, however, failed to stimulate PLD. In addition, the
activation of PLD by 1,25(OH)2D3 or TPA was markedly reduced or accentuated in
stably transfected cells with inhibited or amplified PKC-alpha expression,
respectively. Taken together, these observations indicate that PKC-alpha is
intimately involved in the stimulation of PLD in Caco-2 cells by 1,25(OH)2D3 or
TPA.
PMID- 10198345
TI - 1,25-dihydroxyvitamin D3 but not TPA activates PLD in Caco-2 cells via pp60(c
src) and RhoA.
AB - In the accompanying paper [Khare et al., Am. J. Physiol. 276 (Gastrointest. Liver
Physiol. 39): G993-G1004, 1999], activation of protein kinase C-alpha (PKC-alpha)
was shown to be involved in the stimulation of phospholipase D (PLD) by 1,25
dihydroxyvitamin D3 [1, 25(OH)2D3] and 12-O-tetradecanoylphorbol 13-acetate (TPA)
in Caco-2 cells. Monomeric or heterotrimeric G proteins, as well as pp60(c-src)
have been implicated in PLD activation. We therefore determined whether these
signal transduction elements were involved in PLD stimulation by 1,25(OH)2D3 or
TPA. Treatment with C3 transferase, which inhibits members of the Rho family of
monomeric G proteins, markedly diminished the ability of 1,25(OH)2D3, but not
TPA, to stimulate PLD. Brefeldin A, an inhibitor of ADP-ribosylation factor
proteins, did not, however, significantly reduce the stimulation of PLD by either
of these agents. Moreover, 1,25(OH)2D3, but not TPA, activated pp60(c-src) and
treatment with PP1, a specific inhibitor of the pp60(c-src) family, blocked the
ability of 1,25(OH)2D3 to activate PLD. Pretreatment of cells with pertussis
toxin (PTx) markedly reduced the stimulation of PLD by either agonist. PTx,
moreover, inhibited the stimulation of pp60(c-src) and PKC-alpha by 1,25(OH)2D3.
PTx did not, however, block the membrane translocation of RhoA induced by
1,25(OH)2D3 or inhibit the stimulation of PKC-alpha by TPA. These findings, taken
together with those of the accompanying paper, indicate that although 1,25(OH)2D3
and TPA each activate PLD in Caco-2 cells in part via PKC-alpha, their
stimulation of PLD differs in a number of important aspects, including the
requirement for pp60(c-src) and RhoA in the activation of PLD by 1,25(OH)2D3, but
not TPA. Moreover, the requirement for different signal transduction elements by
1,25(OH)2D3 and TPA to induce the stimulation of PLD may potentially underlie
differences in the physiological effects of these agents in Caco-2 cells.
PMID- 10198346
TI - Mechanisms underlying the anti-inflammatory actions of central corticotropin
releasing factor.
AB - Immune activation of hypothalamic corticotropin-releasing factor (CRF) provides a
negative feedback mechanism to modulate peripheral inflammatory responses. We
investigated whether central CRF attenuates endothelial expression of
intercellular adhesion molecule 1 (ICAM-1) and leukocyte recruitment during
endotoxemia in rats and determined its mechanisms of action. As measured by
intravital microscopy, lipopolysaccharide (LPS) induced a dose-dependent increase
in leukocyte rolling, adhesion, and emigration in mesenteric venules, which was
associated with upregulation of endothelial ICAM-1 expression. Intracisternal
injection of CRF abrogated both the increased expression of ICAM-1 and leukocyte
recruitment. Intravenous injection of the specific CRF receptor antagonist
astressin did not modify leukocyte-endothelial cell interactions induced by a
high dose of LPS but enhanced leukocyte adhesion induced by a low dose. Blockade
of endogenous glucocorticoids but not alpha-melanocyte-stimulating hormone (alpha
MSH) receptors reversed the inhibitory action of CRF on leukocyte-endothelial
cell interactions during endotoxemia. In conclusion, cerebral CRF blunts
endothelial upregulation of ICAM-1 and attenuates the recruitment of leukocytes
during endotoxemia. The anti-inflammatory effects of CRF are mediated by
adrenocortical activation and additional mechanisms independent of alpha-MSH.
PMID- 10198347
TI - Susceptibility of Lewis and Fischer rats to stress-induced worsening of TNB
colitis: protective role of brain CRF.
AB - We assessed the role of central corticotropin-releasing factor (CRF) in stress
induced worsening of colitis in inbred rat strains with hypo (Lewis/N) and hyper
(Fischer344/N) CRF responses to stress. Intracolonic administration of 2,4,6
trinitrobenzenesulfonic acid (TNB) induced colitis of similar severity in both
strains as assessed on day 7 by macroscopic scoring, histological evaluation,
tissue myeloperoxidase (MPO) activity, and decrease in food intake and body
weight. Colitis was inhibited by daily intracerebroventricular injections of CRF
in both strains. Chronic stress (3 h/day, water avoidance or wrap restraint on
alternate days for 6 days) aggravated colitis more in Lewis than Fischer rats (71
and 22% further increase in MPO activity, respectively). The CRF antagonist
astressin injected intracerebroventricularly enhanced the colitis response to
stress and caused mortality in both strains. Fischer rats had higher plasma
corticosterone levels 20 min after stress alone on day 1 and after TNB plus
stress on days 1 and 3 compared with Lewis. These data show that central CRF
restrains the proinflammatory action of stress in experimental colitis.
PMID- 10198348
TI - Polyspecific substrate uptake by the hepatic organic anion transporter Oatp1 in
stably transfected CHO cells.
AB - The rat liver organic anion transporting polypeptide (Oatp1) has been extensively
characterized mainly in the Xenopus laevis expression system as a polyspecific
carrier transporting organic anions (bile salts), neutral compounds, and even
organic cations. In this study, we extended this characterization using a
mammalian expression system and confirm the basolateral hepatic expression of
Oatp1 with a new antibody. Besides sulfobromophthalein [Michaelis-Menten constant
(Km) of approximately 3 microM], taurocholate (Km of approximately 32 microM),
and estradiol- 17beta-glucuronide (Km of approximately 4 microM), substrates
previously shown to be transported by Oatp1 in transfected HeLa cells, we
determined the kinetic parameters for cholate (Km of approximately 54 microM),
glycocholate (Km of approximately 54 microM), estrone-3-sulfate (Km of
approximately 11 microM), CRC-220 (Km of approximately 57 microM), ouabain (Km of
approximately 3,000 microM), and ochratoxin A (Km of approximately 29 microM) in
stably transfected Chinese hamster ovary (CHO) cells. In addition, three new
substrates, taurochenodeoxycholate (Km of approximately 7 microM),
tauroursodeoxycholate (Km of approximately 13 microM), and dehydroepiandrosterone
sulfate (Km of approximately 5 microM), were also investigated. The results
establish the polyspecific nature of Oatp1 in a mammalian expression system and
definitely identify conjugated dihydroxy bile salts and steroid conjugates as
high-affinity endogenous substrates of Oatp1.
PMID- 10198349
TI - NO overproduction by eNOS precedes hyperdynamic splanchnic circulation in portal
hypertensive rats.
AB - Chronic high blood flow and the hyperdynamic circulatory syndrome in portal
hypertension are associated with endothelial constitutive nitric oxide (NO)
synthase (eNOS) upregulation and increased NO release. In portal vein-ligated
(PVL) rats the splanchnic circulation is not yet hyperdynamic on day 3
postoperatively. In vitro perfused superior mesenteric arteries (SMAs) of day 3
PVL and sham rats were challenged with increasing flow rates or the alpha
adrenoreceptor agonist methoxamine (30 and 100 microM) before and after
incubation with the NO inhibitor, Nomega-nitro-L-arginine (L-NNA, 10(-4) M).
Perfusate NO metabolite (NOx) concentrations were measured by chemiluminescence.
PVL rats expressed a significant hyporesponsiveness to increases in flow rate or
methoxamine that was overcome by incubation with L-NNA. The PVL vasculature
showed significantly higher slopes of NOx production vs. flow-induced shear
stress, higher increases in perfusate NOx concentration in response to
methoxamine, and higher eNOS protein levels (Western blot) compared with sham
rats. In conclusion, eNOS-upregulation and increased NO release by the SMA
endothelium occur before the development of the hyperdynamic splanchnic
circulation, suggesting a primary role of NO in the pathogenesis of arterial
vasodilatation.
PMID- 10198350
TI - Vagus nerve modulates secretin binding sites in the rat forestomach.
AB - Secretin is well known for its inhibitory action on gastric motility. It has been
reported that secretin in a physiological dose inhibits gastric motility through
mediation by the vagal afferent pathway. Secretin also elicited relaxation of
carbachol-stimulated rat forestomach muscle strips by binding to its receptors,
suggesting a direct action on this peripheral tissue. We hypothesized that vagal
input may affect the action of secretin by modulating the level of secretin
receptor in the forestomach. Several treatments, including vagal ligation,
vagotomy, perivagal application of capsaicin or colchicine, intravenous infusion
of tetrodotoxin, and intraperitoneal injection of atropine, were performed to
investigate their effects on secretin receptor binding to forestomach membranes.
Specific binding of 125I-labeled secretin to forestomach membranes was
significantly decreased (45%) by vagal ligation, vagotomy (50%), or perivagal
colchicine treatment (40%). On the contrary, specific binding of 125I-secretin
was not affected by perivagal capsaicin treatment, intravenous infusion of
tetrodotoxin, or intraperitoneal injection of atropine. By Scatchard analysis of
the binding data, the capacity of the high-affinity binding sites in forestomach
membranes was found to decrease significantly after vagal ligation compared with
membranes from the sham-operated group. However, the affinity at the high
affinity binding sites, the binding parameters of the low-affinity binding sites,
and binding specificity were not changed. Vagal ligation but not perivagal
capsaicin treatment reduced the inhibitory effect of secretin on bethanechol
stimulated contraction of isolated forestomach muscle strips, causing a right
shift in the dose-response curve. These results suggest that vagal input through
axonal transport plays a significant role on secretin action by modulating the
capacity of secretin binding sites (but not affinity or specificity), at least in
rat forestomach.
PMID- 10198351
TI - TGF-beta1 in liver fibrosis: an inducible transgenic mouse model to study liver
fibrogenesis.
AB - Transforming growth factor-beta1 (TGF-beta1) is a powerful stimulus for collagen
formation in vitro. To determine the in vivo effects of TGF-beta1 on liver
fibrogenesis, we generated transgenic mice overexpressing a fusion gene [C
reactive protein (CRP)/TGF-beta1] consisting of the cDNA coding for an activated
form of TGF-beta1 under the control of the regulatory elements of the inducible
human CRP gene promoter. Two transgenic lines were generated with liver-specific
overexpression of mature TGF-beta1. After induction of the acute phase response
(15 h) with lipopolysaccharide (100 microgram ip), plasma TGF-beta1 levels
reached >600 ng/ml in transgenic animals, which is >100 times above normal plasma
levels. Basal plasma levels of uninduced transgenic animals were about two to
five times above normal. As a consequence of hepatic TGF-beta1 expression, we
could demonstrate marked transient upregulation of procollagen I and procollagen
III mRNA in the liver 15 h after the peak of TGF-beta1 expression. Liver
histology after repeated induction of transgene expression showed an activation
of hepatic stellate cells in both transgenic lines. The fibrotic process was
characterized by perisinusoidal deposition of collagen in a linear pattern. This
transgenic mouse model gives in vivo evidence for the important role of TGF-beta1
in stellate cell activation and liver fibrogenesis. Due to the ability to control
the level of TGF-beta1 expression, this model allows the study of the regulation
and kinetics of collagen synthesis and fibrolysis as well as the degree of
reversibility of liver fibrosis. The CRP/TGF-beta1 transgenic mouse model may
finally serve as a model for the testing of antifibrogenic agents.
PMID- 10198352
TI - Regulation of human airway mucins by acrolein and inflammatory mediators.
AB - Bronchitis, asthma, and cystic fibrosis, marked by inflammation and mucus
hypersecretion, can be caused or exacerbated by airway pathogens or irritants
including acrolein, an aldehyde present in tobacco smoke. To determine whether
acrolein and inflammatory mediators alter mucin gene expression, steady-state
mRNA levels of two airway mucins, MUC5AC and MUC5B, were measured (by RT-PCR) in
human lung carcinoma cells (NCI-H292). MUC5AC mRNA levels increased after >/=0.01
nM acrolein, 10 microM prostaglandin E2 or 15-hydroxyeicosatetraenoic acid, 1.0
nM tumor necrosis factor-alpha (TNF-alpha), or 10 nM phorbol 12-myristate 13
acetate (a protein kinase C activator). In contrast, MUC5B mRNA levels, although
easily detected, were unaffected by these agonists, suggesting that irritants and
associated inflammatory mediators increase mucin biosynthesis by inducing MUC5AC
message levels, whereas MUC5B is constitutively expressed. When transcription was
inhibited, TNF-alpha exposure increased MUC5AC message half-life compared with
control level, suggesting that transcript stabilization is a major mechanism
controlling increased MUC5AC message levels. Together, these findings imply that
irritants like acrolein can directly and indirectly (via inflammatory mediators)
increase airway mucin transcripts in epithelial cells.
PMID- 10198353
TI - Aerosolized GM-CSF ameliorates pulmonary alveolar proteinosis in GM-CSF-deficient
mice.
AB - Surfactant proteins and phospholipids accumulate in the alveolar spaces and lung
tissues of mice deficient in granulocyte-macrophage colony-stimulating factor (GM
CSF), with pathological findings resembling the histology seen in the human
disease pulmonary alveolar proteinosis (PAP). Previous metabolic studies in GM
CSF-deficient [GM(-/-)] mice indicated that defects in surfactant clearance cause
the surfactant accumulation in PAP. In the present study, GM(-/-) mice were
treated daily or weekly with recombinant mouse GM-CSF by aerosol inhalation or
intraperitoneal injection for 4-5 wk. Lung histology, alveolar macrophage
differentiation, and surfactant protein B immunostaining returned toward normal
levels in the GM-CSF aerosol-treated mice. Alveolar and lung tissue saturated
phosphatidylcholine and surfactant protein B concentrations were significantly
decreased after treatment with aerosolized GM-CSF. Cessation of aerosolized GM
CSF for 5 wk resulted in increased saturated phosphatidylcholine pool sizes that
returned to pretreatment levels. In contrast, PAP did not improve in GM(-/-) mice
treated daily for 5 wk with larger doses of systemic GM-CSF. Aerosolized GM-CSF
improved PAP in the GM(-/-) mice, demonstrating that surfactant homeostasis can
be influenced by local administration of GM-CSF to the respiratory tract.
PMID- 10198354
TI - Gialpha but not gqalpha is linked to activation of p21(ras) in human airway
smooth muscle cells.
AB - Airway smooth muscle hypertrophy contributes to the narrowing of asthmatic
airways. Activation of the mitogen-activated protein kinases is an important
event in mediating cell proliferation. Because the monomeric G protein p21(ras)
is an important intermediate leading to activation of mitogen-activated protein
kinases, we questioned which heterotrimeric G protein-coupled receptors were
linked to the activation of p21(ras) in cultured human airway smooth muscle and
which of the heterotrimeric G protein subunits (alpha or betagamma) transmitted
the activation signal. Carbachol and endothelin-1 increased GTP-bound p21(ras) in
a pertussis toxin-sensitive manner [ratio of [32P]GTP to ([32P]GTP + [32P]GDP):
control, 30 +/- 1.7; 3 min of 1 microM carbachol, 39 +/- 1.1; 3 min of 1 microM
endothelin-1, 40 +/- 1.2], whereas histamine, bradykinin, and KCl were without
effect. Transfection of an inhibitor of the G protein betagamma-subunit [the
carboxy terminus (Gly495-Leu689) of the beta-adrenoceptor kinase 1] failed to
inhibit the carbachol-induced activation of p21(ras). These data suggest that Gi-
but not Gq-coupled receptors activate p21(ras) in human airway smooth muscle
cells, and this effect most likely involves the alpha-subunit.
PMID- 10198355
TI - Hypoxia inhibits increased ETB receptor-mediated NO synthesis in hypertensive rat
lungs.
AB - Although hypertensive lungs of chronically hypoxic rats express increased levels
of nitric oxide (NO) synthases (NOSs) and produce increased amounts of NO
containing compounds (NOx) during normoxic ventilation, the level of NO
production during hypoxic exposure is unclear. Because hypoxia inhibits NO
synthesis in normotensive lungs, we investigated whether hypoxic ventilation
inhibited NO synthesis in isolated hypertensive lungs and chronically hypoxic
rats. Measurement of perfusate NOx concentration in hypertensive lungs from male
rats exposed to 4 wk of hypobaric hypoxia showed that basal NOx production was
reduced during hypoxic (0% O2) vs. normoxic (21% O2) ventilation. Similarly,
plasma NOx concentration was lower in chronically hypoxic rats breathing 10% O2
than in those breathing 21% O2. Hypoxic inhibition of lung NOx production was not
prevented by supplementary L-arginine or tetrahydrobiopterin and was not mimicked
by inhibition of Ca2+ influx. However, it was mimicked by inhibition of
constitutive NOS with NG-monomethyl-L-arginine and chelation of intracellular
Ca2+. The endothelin type B-receptor antagonist BQ-788 prevented the increases in
NOx production associated with normoxic ventilation in both isolated hypertensive
lungs and intact chronically hypoxic rats. These results suggest that a reduced
supply of the cosubstrate molecular O2 to NOS counteracts an endothelin type B
receptor-mediated stimulation of NO synthesis in hypertensive rat lungs. Thus,
despite increased NOS protein in the lungs and pulmonary arteries of chronically
hypoxic rats, direct hypoxic inhibition of NO production may contribute to the
development of pulmonary hypertension.
PMID- 10198356
TI - Rearrangement of adherens junctions by transforming growth factor-beta1: role of
contraction.
AB - The signal transduction pathways that lead to disruption of pulmonary endothelial
monolayer integrity by transforming growth factor-beta1 (TGF-beta1) have not been
elucidated. The purpose of this investigation was to determine whether
disassembly of the adherens junction is temporally associated with the TGF-beta1
induced decrease in pulmonary endothelial monolayer integrity. Measurement of
albumin clearance and electrical resistance showed that monolayer integrity
started to decrease between 1 and 2 h post-TGF-beta1 treatment and continued to
slowly decrease over the next 6 h. Immunofluorescence microscopy of monolayers
between 2 and 3 h post-TGF-beta1 showed that beta-catenin, plakoglobin, alpha
catenin, and cadherin-5 were colocalized both at the cell periphery and in newly
formed bands that are perpendicular to the cell-cell border. At 4 h post-TGF
beta1, cells began separating; however, beta- and alpha-catenin, plakoglobin, and
cadherin-5 could still be found at the cell periphery at areas of cell separation
and in strands between separated cells. By 8 h, these junctional proteins were no
longer present at the cell periphery at areas of cell separation. The myosin
light chain kinase inhibitor KT-5926 prevented the TGF-beta1-induced change in
integrity but did not inhibit the formation of actin stress fibers or the
formation of bands containing adherens junction proteins that were perpendicular
to the cell-cell junction. Overall, these results suggest that adherens junction
disassembly occurs after cell separation during TGF-beta1-induced decreases in
pulmonary endothelial monolayer integrity and that the loss of integrity may be
due to the activation of a myosin light chain kinase-dependent signaling cascade.
PMID- 10198357
TI - Regulation of 15-lipoxygenase expression and mucus secretion by IL-4 in human
bronchial epithelial cells.
AB - Our laboratory has recently shown that mucus differentiation of cultured normal
human tracheobronchial epithelial (NHTBE) cells is accompanied by the increased
expression of 15-lipoxygenase (15-LO). We used differentiated NHTBE cells to
investigate the regulation of 15-LO expression and mucus secretion by
inflammatory cytokines. Interleukin (IL)-4 and IL-13 dramatically enhanced the
expression of 15-LO, whereas tumor necrosis factor-alpha, IL-1beta, and
interferon (IFN)-gamma had no effect. These cytokines did not increase the
expression of cyclooxygenase-2, with the exception of a modest induction by IL
1beta. The IL-4-induced 15-LO expression was concentration dependent, and mRNA
and protein expression increased within 3 and 6 h, respectively, after IL-4
treatment. In metabolism studies with intact cells, 15-hydroxyeicosatetraenoic
acid (15-HETE) and 13-hydroxyoctadecadienoic acid (13-HODE) were the major
metabolites formed from exogenous arachidonic acid and linoleic acid. No
prostaglandins were detected. IL-4 treatment dramatically increased the formation
of 13-HODE and 15-HETE compared with that in untreated NHTBE cells, and several
additional 15-LO metabolites were observed. Pretreatment of NHTBE cells with IFN
gamma or dexamethasone did not inhibit the IL-4-induced expression of 15-LO
except at high concentrations (100 ng/ml of IFN-gamma and 10 microM
dexamethasone). IL-4 treatment inhibited mucus secretion and attenuated the
expression of the mucin genes MUC5AC and MUC5B at 12-24 h after treatment.
Addition of 15-HETE precursor and 13-HODE precursor to the cultures did not alter
mucin secretion or mucin gene expression. On the basis of the data presented, we
conclude that the increase in 15-LO expression by IL-4 and attenuation of mucus
secretion may be independent biological events.
PMID- 10198358
TI - Diesel exhaust particles are taken up by human airway epithelial cells in vitro
and alter cytokine production.
AB - The involvement of diesel exhaust particles (DEPs) in respiratory diseases was
evaluated by studying their effects on two in vitro models of human airway
epithelial cells. The cytotoxicity of DEPs, their phagocytosis, and the resulting
immune response were investigated in a human bronchial epithelial cell line
(16HBE14o-) as well as in human nasal epithelial cells in primary culture. DEP
exposure induced a time- and dose-dependent membrane damage. Transmission
electron microscopy showed that DEPs underwent endocytosis by epithelial cells
and translocated through the epithelial cell sheet. Flow cytometric measurements
allowed establishment of the time and dose dependency of this phagocytosis and
its nonspecificity with different particles (DEPs, carbon black, and latex
particles). DEPs also induced a time-dependent increase in interleukin-8,
granulocyte-macrophage colony-stimulating factor, and interleukin-1beta release.
This inflammatory response occurred later than phagocytosis, and its extent seems
to depend on the content of adsorbed organic compounds because carbon black had
no effect on cytokine release. Furthermore, exhaust gas posttreatments, which
diminished the adsorbed organic compounds, reduced the DEP-induced increase in
granulocyte-macrophage colony-stimulating factor release. These results suggest
that DEPs could 1) be phagocytosed by airway epithelial cells and 2) induce a
specific inflammatory response.
PMID- 10198359
TI - Perinatal regulation of the ClC-2 chloride channel in lung is mediated by Sp1 and
Sp3.
AB - Mechanisms responsible for regulation of pulmonary epithelial chloride-channel
expression in the perinatal period are under investigation to better understand
normal lung development and airway disease pathogenesis. The ClC-2 epithelial
chloride channel is regulated by changes in pH and volume and is most abundant in
lung during fetal development. In this study, we identify and sequence the ClC-2
promoter, which is GC rich and lacks a TATA box. By construction of a series of
promoter-luciferase constructs, a 67-bp GC box-containing sequence in the
promoter is shown to be critical to ClC-2 expression in primary and immortalized
fetal lung epithelial cells. Electrophoretic mobility shift assays and antibody
supershifts demonstrate that the Sp1 and Sp3 transcription factors are expressed
in fetal lung nuclei and interact with the GC box sequences in the promoter.
Immunoblotting techniques demonstrate that Sp1 and Sp3 are perinatally
downregulated in the lung with the same temporal sequence as ClC-2
downregulation. This work suggests that Sp1 and Sp3 activate ClC-2 gene
transcription and that reduction in Sp1 and Sp3 at birth explains perinatal
downregulation of ClC-2 in the lung.
PMID- 10198360
TI - Inhibition of factor XIIIa-mediated incorporation of fibronectin into fibrin by
pulmonary surfactant.
AB - Intra-alveolar deposition of exudated plasma proteins is a hallmark of acute and
chronic inflammatory lung diseases. In particular, fibrin and fibronectin may
provide a primary matrix for fibrotic lung remodeling in the alveolar
compartment. The present study was undertaken to explore the effect of two
surfactant preparations on the incorporation of fibronectin into fibrin. We
observed that surfactant phospholipids are associated with insoluble fibrin,
factor XIIIa-cross-linked fibrin, and cross-linked fibrin with incorporated
fibronectin. Factor XIIIa-mediated binding of fibronectin to fibrin was
noticeably altered in the presence of surfactant. Coincubation with two different
commercially available surfactants but not with dipalmitoylphosphatidylcholine
alone resulted in a reduction of fibronectin incorporation into fibrin clots by
approximately one-third. This effect was not dependent on the calcium
concentration. We conclude that 1) factor XIIIa-cross-linked fibrin-fibronectin
is able to incorporate surfactant phospholipids in amounts comparable to fibrin
clots without fibronectin and 2) the binding of fibronectin to fibrin is
partially inhibited in the presence of pulmonary surfactant.
PMID- 10198361
TI - Filaments of surfactant protein A specifically interact with corrugated surfaces
of phospholipid membranes.
AB - Pulmonary surfactant, a mixture of lipids and surfactant proteins (SPs), plays an
important role in respiration and gas exchange. SP-A, the major SP, exists as an
octadecamer that can self-associate to form elongated protein filaments in vitro.
We have studied here the association of purified bovine SP-A with lipid vesicle
bilayers in vitro with negative staining with uranyl acetate and transmission
electron microscopy. Native bovine surfactant was also examined by transmission
electron microscopy of thinly sectioned embedded material. Lipid vesicles made
from dipalmitoylphosphatidylcholine and egg phosphatidylcholine (1:1 wt/wt)
generally showed a smooth surface morphology, but some large vesicles showed a
corrugated one. On the smooth-surfaced vesicles, SP-As primarily interacted in
the form of separate octadecamers or as multidirectional protein networks. On the
surfaces of the striated vesicles, SP-As primarily formed regularly spaced
unidirectional filaments. The mean spacing between adjacent striations and
between adjacent filaments was 49 nm. The striated surfaces were not essential
for the formation of filaments but appeared to stabilize them. In native
surfactant preparations, SP-A was detected in the dense layers. This latter
arrangement of the lipid bilayer-associated SP-As supported the potential
relevance of the in vitro structures to the in vivo situation.
PMID- 10198362
TI - Formation of membrane lattice structures and their specific interactions with
surfactant protein A.
AB - Biological membranes exist in many forms, one of which is known as tubular myelin
(TM). This pulmonary surfactant membranous structure contains elongated tubes
that form square lattices. To understand the interaction of surfactant protein
(SP) A and various lipids commonly found in TM, we undertook a series of
transmission-electron-microscopic studies using purified SP-A and lipid vesicles
made in vitro and also native surfactant from bovine lung. Specimens from in
vitro experiments were negatively stained with 2% uranyl acetate, whereas fixed
native surfactant was delipidated, embedded, and sectioned. We found that
dipalmitoylphosphatidylcholine-egg phosphatidylcholine (1:1 wt/wt) bilayers
formed corrugations, folds, and predominantly 47-nm-square latticelike
structures. SP-A specifically interacted with these lipid bilayers and folds. We
visualized other proteolipid structures that could act as intermediates for
reorganizing lipids and SP-As. Such a reorganization could lead to the
localization of SP-A in the lattice corners and could explain, in part, the
formation of TM-like structures in vivo.
PMID- 10198363
TI - Effects of endotoxin on surfactant protein A and D stimulation of NO production
by alveolar macrophages.
AB - Surfactant protein (SP) A and SP-D affect numerous functions of immune cells
including enhancing phagocytosis of bacteria and production of reactive species.
Previous studies have shown that SP-A and SP-D bind to a variety of bacteria and
to the lipopolysaccharide (LPS) components of their cell walls. In addition,
purified preparations of SPs often contain endotoxin. The goals of this study
were 1) to evaluate the effects of SP-A and SP-D and complexes of SPs and LPS on
the production of nitric oxide metabolites by rat alveolar macrophages and 2) to
evaluate methods for the removal of endotoxin with optimal recovery of SP.
Incubation of SP-A or SP-D with polymyxin, 100 mM N-octyl-beta-D-glucopyranoside,
and 2 mM EDTA followed by dialysis was the most effective method of those tested
for reducing endotoxin levels. Commonly used storage buffers for SP-D, but not
for SP-A, inhibited the detection of endotoxin. There was a correlation between
the endotoxin content of the SP-A and SP-D preparations and their ability to
stimulate production of nitrite by alveolar macrophages. SP-A and SP-D treated as
described above to remove endotoxin did not stimulate nitrite production. These
studies suggest that the functions of SP-A and SP-D are affected by endotoxin and
illustrate the importance of monitoring SP preparations for endotoxin
contamination.
PMID- 10198364
TI - Characterization of the internalization pathways for the cystic fibrosis
transmembrane conductance regulator.
AB - Mutations in the gene encoding the cystic fibrosis (CF) transmembrane conductance
regulator (CFTR) chloride channel give rise to the most common lethal genetic
disease of Caucasian populations, CF. Although the function of CFTR is primarily
related to the regulation of apical membrane chloride permeability, biochemical,
immunocytochemical, and functional studies indicate that CFTR is also present in
endosomal and trans Golgi compartments. The molecular pathways by which CFTR is
internalized into intracellular compartments are not fully understood. To define
the pathways for CFTR internalization, we investigated the association of CFTR
with two specialized domains of the plasma membrane, clathrin-coated pits and
caveolae. Internalization of CFTR was monitored after cell surface biotinylation
and quantitation of cell surface CFTR levels after elution of cell lysates from a
monomeric avidin column. Cell surface levels of CFTR were determined after
disruption of caveolae or clathrin-coated vesicle formation. Biochemical assays
revealed that disrupting the formation of clathrin-coated vesicles inhibited the
internalization of CFTR from the plasma membrane, resulting in a threefold
increase in the steady-state levels of cell surface CFTR. In contrast, the levels
of cell surface CFTR after disruption of caveolae were not different from those
in control cells. In addition, although our studies show the presence of caveolin
at the apical membrane domain of human airway epithelial cells, we were unable to
detect CFTR in purified caveolae. These results suggest that CFTR is
constitutively internalized from the apical plasma membrane via clathrin-coated
pits and that CFTR is excluded from caveolae.
PMID- 10198365
TI - PKC role in mechanically induced Ca2+ waves and ATP-induced Ca2+ oscillations in
airway epithelial cells.
AB - Mechanical stimulation of airway epithelial cells generates the Ca2+ mobilization
messenger inositol 1,4,5-trisphosphate and the protein kinase (PK) C activator
diacylglycerol. Inositol 1,4,5-trisphosphate diffuses through gap junctions to
mediate intercellular communication of the mechanical stimulus (a "Ca2+ wave");
the role that diacylglycerol-activated PKC might play in the response is unknown.
Using primary cultures of rabbit tracheal cells, we show that 12-O
tetradecanoylphorbol 13-acetate- or 1, 2-dioctanyl-sn-glycerol-induced activation
of PKC slows the Ca2+ wave, decreases the amplitude of induced intracellular free
Ca2+ concentration ([Ca2+]i) increases, and decreases the number of affected
cells. The PKC inhibitors bisindolylmaleimide and Go 6976 slowed the spread of
the wave but did not change the number of affected cells. We show that ATP
induced [Ca2+]i increases and oscillations, responses independent of
intercellular communication, were inhibited by PKC activators.
Bisindolylmaleimide decreased the amplitude of ATP-induced [Ca2+]i increases and
blocked oscillations, suggesting that PKC has an initial positive effect on Ca2+
mobilization and then mediates feedback inhibition. PKC activators also reduced
the [Ca2+]i increase that followed thapsigargin treatment, indicating a PKC
effect associated with the Ca2+ release mechanism.
PMID- 10198366
TI - Abrogation of cyclin D1 expression predisposes lung cancer cells to serum
deprivation-induced apoptosis.
AB - Cyclin D1 antisense (D1AS)-transfected lung epithelial cell lines were serum
deprived and then analyzed for three hallmarks of apoptosis: appearance of single
strand DNA breaks, alteration of apoptosis-related protein expression, and
induction of chromatin condensation. Single-strand DNA breaks appeared at
significant levels 24 h after serum deprivation, whereas induction of chromatin
condensation was observed after 72 h. The antioxidants dimethyl sulfoxide,
ascorbate, and glutathione, as well as insulin-like growth factor-I, inhibited
induction of DNA damage in this assay. Additionally, proliferating cell nuclear
antigen expression is completely suppressed in the D1AS cells, indicating a
mechanism to explain the reduced capacity for DNA repair. Increased expression of
cyclin D1, which is a common lesion in lung cancer, may thus prevent induction of
apoptosis in an oxidizing and growth factor-poor environment. Reducing cyclin D1
expression in lung cancer cells by expression of D1AS RNA disrupted these
protective pathways.
PMID- 10198367
TI - Carbon monoxide provides protection against hyperoxic lung injury.
AB - Findings in recent years strongly suggest that the stress-inducible gene heme
oxygenase (HO)-1 plays an important role in protection against oxidative stress.
Although the mechanism(s) by which this protection occurs is poorly understood,
we hypothesized that the gaseous molecule carbon monoxide (CO), a major by
product of heme catalysis by HO-1, may provide protection against oxidative
stress. We demonstrate here that animals exposed to a low concentration of CO
exhibit a marked tolerance to lethal concentrations of hyperoxia in vivo. This
increased survival was associated with highly significant attenuation of
hyperoxia-induced lung injury as assessed by the volume of pleural effusion,
protein accumulation in the airways, and histological analysis. The lungs were
completely devoid of lung airway and parenchymal inflammation, fibrin deposition,
and pulmonary edema in rats exposed to hyperoxia in the presence of a low
concentration of CO. Furthermore, exogenous CO completely protected against
hyperoxia-induced lung injury in rats in which endogenous HO enzyme activity was
inhibited with tin protoporphyrin, a selective inhibitor of HO. Rats exposed to
CO also exhibited a marked attenuation of hyperoxia-induced neutrophil
infiltration into the airways and total lung apoptotic index. Taken together, our
data demonstrate, for the first time, that CO can be therapeutic against
oxidative stress such as hyperoxia and highlight possible mechanism(s) by which
CO may mediate these protective effects.
PMID- 10198369
TI - Insulin-like growth factor I improves renal function in patients with end-stage
chronic renal failure.
AB - There is no pharmacological treatment to increase the glomerular filtration rate
in end-stage renal disease (ESRD). The administration of 100 microgram/kg of
insulin-like growth factor (IGF) I twice a day to patients with ESRD increases
inulin clearance. However, its effect is short-lived and IGF-I has major side
effects when given this way. To assess whether the use of a lower intermittent
dose of IGF-I would effect sustained improved function with tolerable side
effects we performed 1) a prospective open-labeled 24-day trial in which we
enrolled five patients and 2) a 31-day randomized, double-blinded, placebo
controlled trial in which we enrolled 10 patients. Patients with ESRD [creatinine
clearance of <15 ml. min-1. (1.73 m2)-1] and scheduled to initiate renal
replacement therapy received subcutaneous IGF-I, 50 microgram. kg-1. day-1, or
vehicle. Treatment with IGF I resulted in significantly increased glomerular
filtration rates (inulin clearances) during the 3rd and 4th wk of therapy in both
prospective and double-blinded studies. Vehicle had no effect. No patient
required discontinuation of drug secondary to side effects. We conclude that IGF
I effects sustained improvement of renal function (clearances comparable to those
generally achieved by dialysis) in patients with ESRD and is well tolerated.
PMID- 10198368
TI - Cold acclimation of guinea pig depressed contraction of cardiac papillary muscle.
AB - Guinea pigs were exposed to 5 degrees C for 3 wk, and the contractions of
myocardial papillary muscle were compared with preparations dissected from
control animals kept at approximately 25 degrees C. Developed tension of the
papillary muscle per cross-sectional area was significantly (t-test, P < 0.05)
decreased after cold exposure (19,200 +/- 8,160 vs. 3,020 +/- 2,890 dyne/cm2; 1
Hz). Time to peak tension was significantly faster in cold-exposed guinea pigs
(126.4 +/- 11.1 ms; 1 Hz) than in controls (162.7 +/- 8. 7 ms). The magnitude of
the developed tension after application of ryanodine (2 mM) to muscles from cold
exposed animals was decreased to 37.5 +/- 8.3% of control at 1 Hz, whereas in
muscles from control animals, tension was decreased to 82.4 +/- 7.7%. The
ryanodine-sensitive component of contraction was not significantly changed in
control guinea pigs at frequencies >0.5 Hz, whereas in muscles from cold
acclimated guinea pigs, there was a "positive staircase." These results suggested
that reversal of the Na+/Ca2+ exchanger is predominantly involved in the positive
staircase in control guinea pigs, whereas rate-dependent increases in the Ca2+
store in the sarcoplasmic reticulum may be involved in the staircase after cold
acclimation.
PMID- 10198370
TI - Glutamatergic and dopaminergic contributions to rat bladder hyperactivity after
cerebral artery occlusion.
AB - The contribution of glutamatergic and dopaminergic mechanisms to bladder
hyperactivity after left middle cerebral artery occlusion was evaluated by
determining the effects of intravenous cumulative doses of an N-methyl-D
aspartate (NMDA) glutamatergic antagonist (MK-801) and D1-selective (Sch-23390),
D2-selective (sulpiride), or nonselective (haloperidol) dopaminergic antagonists
on bladder activity in sham-operated (SO) and cerebral-infarcted (CI) rats. MK
801 (1 and 10 mg/kg) or sulpiride (3-30 mg/kg) significantly increased bladder
capacity (BC) in CI but decreased or had no effect, respectively, on BC in SO.
Sch-23390 (0.1-3 mg/kg) decreased BC in both SO and CI. In both CI and SO, low
doses of haloperidol (0.1-1 mg/kg) increased BC, but a higher dose (3 mg/kg)
reversed this effect. Administration of haloperidol (0.3 mg/kg) or sulpiride (10
mg/kg) in combination with MK-801 (0.01-10 mg/kg) markedly increased BC in CI but
produced small decreases or increases in BC depending on the dose of MK-801 in
SO. These results indicate that the bladder hyperactivity induced by cerebral
infarction is mediated in part by NMDA glutamatergic and D2 dopaminergic
excitatory mechanisms.
PMID- 10198371
TI - Electrical response properties of avian lagena type II hair cells: a model system
for vestibular filtering.
AB - Data presented represent the first electrical recordings from avian lagena type
II hair cells. The perforated-patch variant of the whole cell recording technique
was used to investigate how the macroscopic currents shaped the voltage response
of the hair cells. Voltage-clamp data separated cells into two broad classes on
the basis of differences in activation rates, rates and degree of inactivation,
and pharmacological sensitivity. Current-clamp recordings revealed low-quality
membrane voltage oscillations (Qc < 1) during pulse current injections.
Oscillation frequency correlated with activation rate of the macroscopic
currents. The quality of membrane oscillations (Qc) varied linearly with
frequency for cells with little inactivation. For cells with rapid inactivation,
no relationship was found between Qc and frequency. Rapid inactivation may serve
to extend the bandwidth of vestibular hair cells. The frequency measured from
voltage responses to pulsed currents may reflect the corner frequency of the
cell. The filtering properties of avian lagena hair cells are like those found in
all other vestibular end organs, suggesting that the electrical membrane
properties of these cells are not responsible for specializing them to a
particular stimulus modality.
PMID- 10198372
TI - Time course of myosin heavy chain transitions in neonatal rats: importance of
innervation and thyroid state.
AB - During the postnatal period, rat limb muscles adapt to weight bearing via the
replacement of embryonic (Emb) and neonatal (Neo) myosin heavy chains (MHCs) by
the adult isoforms. Our aim was to characterize this transition in terms of the
six MHC isoforms expressed in skeletal muscle and to determine the importance of
innervation and thyroid hormone status on the attainment of the adult MHC
phenotype. Neonatal rats were made hypothyroid via propylthiouracil (PTU)
injection. In normal and PTU subgroups, leg muscles were unilaterally denervated
at 15 days of age. The MHC profiles of plantaris (PLN) and soleus (Sol) muscles
were determined at 7, 14, 23, and 30 days postpartum. At day 7, the Sol MHC
profile was 55% type I, 30% Emb, and 10% Neo; in the PLN, the pattern was 60% Neo
and 25% Emb. By day 30 the Sol and PLN had essentially attained an adult MHC
profile in the controls. PTU augmented slow MHC expression in the Sol, whereas in
the PLN it markedly repressed IIb MHC by retaining neonatal MHC expression.
Denervation blunted the upregulation of IIb in the PLN and of Type I in the Sol
and shifted the pattern to greater expression of IIa and IIx MHCs in both
muscles. In contrast to previous observations, these findings collectively
suggest that both an intact thyroid and innervation state are obligatory for the
attainment of the adult MHC phenotype, particularly in fast-twitch muscles.
PMID- 10198373
TI - RVLM and raphe differentially regulate sympathetic outflows to splanchnic and
brown adipose tissue.
AB - To determine whether neurons in the rostral raphe pallidus (RPa) specifically
control the sympathetic nerve activity to brown adipose tissue (BAT SNA), thereby
regulating adipocyte metabolism and BAT thermogenesis, the responses in BAT SNA
to disinhibition of RPa neurons and to disinhibition of neurons in the vasomotor
region of the rostral ventrolateral medulla (RVLM) were compared with those in
splanchnic (Spl) SNA, which primarily regulates visceral vasoconstriction. In
urethan-chloralose-anesthetized ventilated rats, both acute hypothermia and
microinjection of bicuculline into RPa produced significantly larger increases in
BAT SNA (542 and 1,949% of control) than in Spl SNA (19 and 24% of control). The
enhanced burst discharge in BAT SNA was not coherent with that in Spl SNA or with
the arterial pressure (AP) at any frequency except the central respiratory
frequency. Microinjections of bicuculline into RVLM evoked increases in Spl SNA
(86% of control) and AP (32 mmHg), but reduced BAT SNA to low, normothermic
levels. Microinjections of muscimol into RVLM reduced Spl SNA (-82% of control)
and AP (-59 mmHg), but did not prevent the increase in BAT SNA after
disinhibition of RPa neurons. These results indicate that the neural networks
generating BAT SNA in response to disinhibition of RPa neurons are independent of
those generating basal Spl SNA and support a model in which sympathetic outflow
to tissues involved in thermoregulation and metabolism is regulated by central
pathways, including neurons in RPa, that are distinct from those involved in the
sympathetic control of the cardiovascular system.
PMID- 10198374
TI - Neonatal uninephrectomy causes hypertension in adult rats.
AB - This study was designed to test the hypothesis that a reduced number of nephrons
from birth leads to increased arterial pressure in adulthood. Newborn Sprague
Dawley rat pups were uninephrectomized during the first 24 h after birth. In
chronically instrumented adult animals (approximately 22 wk), mean arterial
pressure on a normal (0.20%)-Na+ diet was higher in uninephrectomized rats (133
+/- 2 mmHg vs. 121 +/- 2 mmHg in controls, P < 0.0001). Body weights were not
significantly different, but the total kidney-to-body weight ratio was
significantly reduced by 14% in adult uninephrectomized animals (P < 0.05).
Glomerular filtration rate was reduced by approximately 30% in uninephrectomized
rats (1.84 +/- 0.09 vs. 2.63 +/- 0.14 ml/min, P < 0.0002), and effective renal
plasma flow was reduced to a lesser degree (6.37 +/- 0.38 vs. 7.87 +/- 0.51
ml/min, P < 0.03), such that the filtration fraction was also reduced (0.291 +/-
0.007 vs. 0.338 +/- 0.014, P < 0.01). After 7-10 days on a high (3.15%)-Na+ diet,
arterial pressure increased more in uninephrectomized animals than in controls
(20 +/- 3 vs. 1 +/- 1 mmHg, P < 0.003). Thus surgical removal of 50% of the
nephrons, when done during development, caused reduced renal function and a salt
sensitive hypertension in adulthood. These data suggest that a reduced nephron
endowment from birth, caused by genetic and/or perinatal environmental factors,
could contribute to essential hypertension in adulthood.
PMID- 10198375
TI - Correlation of ventricular mechanosensory neurite activity with myocardial
sensory field deformation.
AB - The mechanosensory activity generated by ventricular epicardial sensory neurites
associated with afferent axons in thoracic sympathetic nerves was correlated with
sensory field deformation (long axis, short axis, and transmural dimension
changes), regional intramyocardial pressure, and ventricular chamber pressure in
anesthetized dogs. Ventricular mechanosensory neurites generated activity that
correlated best with strain developed along either the long or short axis of
their epicardial sensory fields in most instances. Activity did not correlate
normally to local wall thickness or to regional wall or chamber pressure
development in most cases. During premature ventricular contractions, the
activity generated by these sensory neurites correlated best with maximum strain
developed along at least one sensory field epicardial vector. Identified sensory
neurites were also activated by local application of the chemical bradykinin (10
microM) or by local ischemia. These data indicate that the activity generated by
most ischemia-sensitive ventricular epicardial sensory neurites associated with
afferent axons in sympathetic nerves is dependent on not only their local
chemical milieu but on local mechanical deformation along at least one epicardial
vector of their sensory fields.
PMID- 10198376
TI - Influence of bioenergetic stress on heat shock protein gene expression in
nucleated red blood cells of fish.
AB - The physiological and biochemical signals that induce stress protein (HSP)
synthesis remain conjectural. In this study, we used the nucleated red blood
cells from rainbow trout, Oncorhynchus mykiss, to address the interaction between
energy status and HSP gene expression. Heat shock (25 degrees C) did not
significantly affect ATP levels but resulted in an increase in HSP70 mRNA.
Hypoxia alone did not induce HSP transcription in these cells despite a
significant depression in ATP. Inhibition of oxidative phosphorylation with
azide, in the absence of thermal stress, decreased ATP by 56% and increased
lactate production by 62% but did not induce HSP gene transcription. Inhibition
of oxidative phosphorylation and glycolysis with azide and iodoacetic acid
respectively, decreased ATP by 79% and prevented lactate production, but did not
induce either HSP70 or HSP30 gene transcription in these cells. This study
demonstrates that a reduction in the cellular energy status will not induce
stress protein gene transcription in rainbow trout red blood cells and may, in
fact, limit induction during extreme metabolic inhibition.
PMID- 10198377
TI - Interactions between gastric volume and duodenal nutrients in the control of
liquid gastric emptying.
AB - We examined the relationships between gastric volume and duodenal glucose load in
the regulation of gastric emptying in adult male rhesus monkeys. Intragastric
glucose loads (0.125 g/ml) of volumes ranging from 150 to 375 ml empty from the
stomach at the same rate from 20 to 120 min. However, to achieve these equivalent
emptying rates, progressively larger volumes were emptied in the initial 20 min
with increasing gastric volume. Duodenal glucose infusions dose dependently
inhibited the 10-min emptying of various volumes of intragastric saline. Although
increasing gastric volume resulted in increased emptying, duodenal glucose right
shifted the relationship between initial gastric volume and volume emptied. These
data demonstrate that liquid nutrient gastric emptying represents an interaction
between gastric volume and nutrient-induced duodenal feedback. For controlled
duodenal caloric delivery rates to be established, sufficient nutrient emptying
must occur to increase the magnitude of duodenal feedback to withhold a given
gastric volume.
PMID- 10198378
TI - Brown adipose tissue triacylglycerol synthesis in rats adapted to a high-protein,
carbohydrate-free diet.
AB - Adaptation of rats to a high-protein, carbohydrate-free (HP) diet induced a
marked reduction of brown adipose tissue (BAT) fatty acid (FA) synthesis from
both 3H2O and [14C]glucose in vivo, with pronounced decreases in the activities
of four enzymes associated with lipogenesis: glucose-6-phosphate dehydrogenase,
malic enzyme, citrate lyase, and acetyl-CoA carboxylase. In both HP-adapted and
control rats, in vivo incorporation of 3H2O and [14C]glucose into BAT glyceride
glycerol was much higher than into FA. It could be estimated that most of the
glycerol synthetized was used to esterify preformed FA. Glycerol synthesis from
nonglucose sources (glyceroneogenesis) was increased in BAT from HP rats, as
evidenced by an increased capacity of tissue fragments to incorporate [1
14C]pyruvate into glycerol and by a fourfold increase in the activity of
phosphoenolpyruvate carboxykinase activity, a key glyceroneogenic enzyme. The
data suggest that high rates of glyceroneogenesis and of esterification of
preformed FA in BAT from HP-adapted rats are essential for preservation of tissue
lipid stores, necessary for heat generation when BAT is recruited in nonshivering
thermogenesis.
PMID- 10198379
TI - Central and peripheral administration of endothelin-1 induces an increase in
blood pressure in conscious trout.
AB - The central and peripheral cardiovascular effects of endothelin (ET)-1 and ET-3
were investigated in conscious rainbow trout. Both intracerebroventricular and
intra-arterial injections of ET-1 (6. 25-25 pmol) but not ET-3 (25 pmol) caused a
dose-dependent increase in mean dorsal aortic blood pressure and a concomitant
decrease in heart rate. The hypertensive effects induced by intra-arterial and
intracerebroventricular injection of ET-1 were associated with a significant (P <
0.05) increase in systemic vascular resistance. Intracerebroventricular injection
of ET-1 induced a twofold higher pressor response than that caused by intra
arterial injection of ET-1 and provoked a barostatic gain that was reduced by 2.5
to 3-fold compared with that calculated after intra-arterial administration of
the peptide. The ET receptor antagonist bosentan significantly (P < 0.05)
attenuated these responses regardless of the route of administration. Finally,
intra-arterial injection of ET-1 did not significantly modify plasma cortisol
level. The present data demonstrate that intracerebroventricular and intra
arterial administration of very low doses of ET-1 produces hypertension in
conscious trout. The lack of effect of ET-3 indicates that the hemodynamic
actions of ET-1 are mediated both centrally and peripherally through ETA
receptors.
PMID- 10198380
TI - Intracerebroventricular injection of TNF-alpha promotes sleep and is recovered in
cervical lymph.
AB - Recent studies have shown that the central nervous system (CNS) communicates with
the periphery by the drainage of cerebrospinal fluid and brain interstitial fluid
into blood and lymph. We hypothesized that tumor necrosis factor (TNF)-alpha
would not only influence the CNS by promoting sleep but also would be directly
transmitted into the peripheral immune system. Five hundred nanograms of 125I
labeled TNF-alpha were injected into the lateral ventricles of the brain of six
sheep and sampled in venous blood and cervical and prescapular lymph every 30 min
for 6 h. 125I-TNF-alpha was measured in lymph nodes and control fat, skin, and
muscle tissues 6 h postinjection. 125I-TNF-alpha was detected in the cervical
lymphatics within the first 30 min and peaked within 2-3 h. 125I-TNF-alpha counts
were elevated in the nodes of the head and neck region. Polysomnographic
recordings of four animals showed that TNF-alpha induced a significant increase
in slow-wave sleep at postinjection hours 4 and 5. CNS TNF-alpha and its direct
drainage into the lymphatic system may influence both the sleeping/waking brain
and peripheral immune functions.
PMID- 10198381
TI - Agonist-specific impairment of coronary vascular function in genetically altered,
hyperlipidemic mice.
AB - The objectives of the present study were to 1) examine mechanisms involved in
endothelium-dependent responses of coronary arteries from normal mice and 2)
determine whether vascular responses of coronary arteries are altered in two
genetic models of hypercholesterolemia [apolipoprotein E (apoE)-deficient mice
(apoE -/-) and combined apoE and low-density lipoprotein receptor (LDLR)
deficient mice (apoE + LDLR -/-)]. Plasma cholesterol levels were higher in both
apoE -/- and apoE + LDLR -/- compared with normal mice on normal and high
cholesterol diets (normal chow: normal 110 +/- 5 mg/dl, apoE -/- 680 +/- 40
mg/dl, apoE + LDLR -/- 810 +/- 40 mg/dl; high-cholesterol chow: normal 280 +/- 60
mg/dl, apoE -/- 2,490 +/- 310 mg/dl, apoE + LDLR -/- 3,660 +/- 290 mg/dl).
Coronary arteries from normal (C57BL/6J), apoE -/-, and apoE + LDLR -/- mice were
isolated and cannulated, and diameters were measured using videomicroscopy. In
normal mice, vasodilation in response to ACh and serotonin was markedly reduced
by 10 microM Nomega-nitro-L-arginine (an inhibitor of nitric oxide synthase) or
20 microM 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; an inhibitor of
soluble guanylate cyclase). Vasodilation to nitroprusside, but not papaverine,
was also inhibited by ODQ. Dilation of arteries from apoE -/- and apoE + LDLR -/-
mice on normal diet in response to ACh was similar to that observed in normal
mice. In contrast, dilation of arteries in response to serotonin from apoE -/-
and apoE + LDLR -/- mice was impaired compared with normal. In arteries from both
apoE -/- and apoE + LDLR -/- mice on high-cholesterol diet, dilation to ACh was
decreased. In apoE + LDLR -/- mice on high-cholesterol diet, dilation of coronary
arteries to nitroprusside was increased. These findings suggest that dilation of
coronary arteries from normal mice in response to ACh and serotonin is dependent
on production of nitric oxide and activation of soluble guanylate cyclase.
Hypercholesterolemia selectively impairs dilator responses of mouse coronary
arteries to serotonin. In the absence of both apoE and the LDL receptor, high
levels of cholesterol result in a greater impairment in coronary endothelial
function.
PMID- 10198382
TI - Estrogen enhancement of baroreflex sensitivity is centrally mediated.
AB - We have recently shown that estrogen enhances baroreceptor control of reflex
bradycardia in conscious rats. The present study replicated this finding in
pentobarbital sodium-anesthetized rats, and the study was extended to investigate
whether this effect of estrogen is centrally or peripherally mediated.
Hemodynamic responses to electrical stimulation of the central end of the aortic
depressor or the vagal efferent nerve were evaluated in pentobarbital sodium
anesthetized sham-operated (SO), ovariectomized (OVX), and OVX estradiol-treated
Sprague-Dawley rats. Phenylephrine (1-16 microgram/kg iv) elicited dose-dependent
pressor and bradycardic responses. Regression analysis of the baroreflex curves,
relating changes in mean arterial pressure and heart rate, revealed a
significantly smaller baroreflex sensitivity in OVX compared with SO anesthetized
rats (-0.54 +/- 0.05 and -0.91 +/- 0.12 beats. min-1. mmHg-1, respectively; P <
0.05). Treatment of OVX rats with 17beta-estradiol (E2, 50 microgram. kg-1. day-1
for 2 days subcutaneously) significantly enhanced baroreflex sensitivity to a
level similar to that of SO rats (P < 0.05). The enhancing effect of E2 on the
baroreflex-mediated bradycardia, observed in conscious and anesthetized rats,
seems to be selective because the baroreflex-mediated tachycardic responses
measured in a separate group of conscious rats were not altered by ovariectomy or
E2 administration. Electrical stimulation of the aortic nerve elicited frequency
dependent depressor and bradycardic responses that were significantly smaller in
OVX compared with SO values (P < 0.05). Treatment of OVX rats with E2 restored
the hemodynamic responses to aortic stimulation to near SO levels. On the other
hand, hemodynamic responses to vagal stimulation were not affected by OVX or
treatment with E2. These findings suggest that enhancement of reflex bradycardia
by estrogen is centrally mediated and involves interaction with central
projections of the aortic nerve.
PMID- 10198383
TI - Long-term CCK-leptin synergy suggests a role for CCK in the regulation of body
weight.
AB - The gut peptide CCK is a nutrient-related signal important to the control of food
intake. In the present studies, we observed that a single intraperitoneal
injection of CCK (1-2 microgram/kg) given 2-3 h after intracerebroventricular
leptin (2-5 microgram) reduced body weight and chow intake over the ensuing 48 h
more than did leptin alone. CCK alone had no effect on either 48-h chow intake or
body weight but significantly reduced feeding during a 30-min sucrose test.
However, reduction of 30-min sucrose intake by CCK was not enhanced by prior
intracerebroventricular leptin. The present data suggest that CCK can contribute
to the regulation of body weight when central leptin levels are elevated.
PMID- 10198384
TI - Fatty acid oxidation affects food intake by altering hepatic energy status.
AB - Inhibition of fatty acid oxidation stimulates feeding behavior in rats. To
determine whether a decrease in hepatic fatty acid oxidation triggers this
behavioral response, we compared the effects of different doses of methyl
palmoxirate (MP), an inhibitor of fatty acid oxidation, on food intake with those
on in vivo and in vitro liver and muscle metabolism. Administration of 1 mg/kg MP
selectively decreased hepatic fatty acid oxidation but did not stimulate food
intake. In contrast, feeding behavior increased in rats given 5 or 10 mg/kg MP,
which inhibited hepatic fatty acid oxidation to the same extent as did the low
dose but in addition suppressed fatty acid oxidation in muscle and produced a
marked depletion of liver glycogen. Dose-related increases in food intake tracked
dose-related reductions in liver ATP content, ATP-to-ADP ratio, and
phosphorylation potential. The findings suggest that a decrease in hepatic fatty
acid oxidation can stimulate feeding behavior by reducing hepatic energy
production.
PMID- 10198385
TI - Midline medullary depressor responses are mediated by inhibition of RVLM
sympathoexcitatory neurons in rats.
AB - Mechanisms underlying the depressor and sympathoinhibitory responses evoked from
the caudal medullary raphe (MR) region were investigated in pentobarbital sodium
anesthetized, paralyzed rats. Intermittent electrical stimulation (0.5 Hz, 0.5-ms
pulses, 200 microA) of the MR elicited a mixed sympathetic response that
consisted of a long-latency sympathoexcitatory (SE) peak (onset = 146 +/- 7 ms)
superimposed on an inhibitory phase (onset = 59 +/- 10 ms). Chemical stimulation
of the MR (glutamate; Glu) most frequently elicited depressor responses
accompanied by inhibition of sympathetic nerve discharge. Occasionally, these
responses were preceded by transient pressor and SE responses. We examined the
influence of intermittent electrical stimulation (0.5 Hz, 0.5-ms pulses, 25-200
microA) and Glu stimulation of the MR on the discharge of rostral ventrolateral
medulla (RVLM) premotor SE neurons. Peristimulus-time histograms of RVLM unit
discharge featured a prominent inhibitory phase in response to MR stimulation
(onset = 20 +/- 2 ms; duration = 42 +/- 4 ms; n = 12 units). Glu stimulation of
the MR reduced blood pressure (-37 +/- 2 mmHg, n = 19) and inhibited the
discharge of RVLM SE neurons (15 of 19 neurons). Depressor and sympathoinhibitory
responses elicited by chemical and electrical stimulation of the MR region are
mediated by inhibition of RVLM premotor SE neurons and withdrawal of sympathetic
vasomotor discharge.
PMID- 10198386
TI - Reduced glucose availability attenuates circadian responses to light in mice.
AB - To test whether circadian responses to light are modulated by decreased glucose
availability, we analyzed photic phase resetting of the circadian rhythm of
locomotor activity in mice exposed to four metabolic challenges: 1) blockade of
glucose utilization induced by 2-deoxy-D-glucose (2-DG), 2) fasting (food was
removed for 30 h), 3) insulin administration, and 4) insulin treatment after
fasting. In mice housed in constant darkness, light pulses applied during early
subjective night induced phase delays of the rhythm of locomotor activity,
whereas light pulses applied during late subjective night caused phase advances.
There was an overall reduction of light-induced phase shifts, with a more
pronounced effect for delays, in mice pretreated with 500 mg/kg ip 2-DG compared
with mice injected with saline. Administration of glucose with 2-DG prevented the
reduction of light-induced phase delays. Furthermore, phase delays were reduced
in fed mice pretreated with 5 IU/kg sc insulin and in fasted mice injected with
saline or insulin compared with control fed mice. These results show that
circadian responses to light are reduced when brain glucose availability is
decreased, suggesting a metabolic modulation of light-induced phase shifts.
PMID- 10198387
TI - Elevation of blood pressure by genetic and pharmacological disruption of the ETB
receptor in mice.
AB - Exogenously administered endothelin (ET) elicits both pressor and depressor
responses through the ETA and/or the ETB receptor on vascular smooth muscle cells
and ETB on endothelial cells. To test whether ETB has pressor or depressor
effects under basal physiological conditions, we determined arterial blood
pressure (BP) in ETB-deficient mice obtained by crossing inbred mice heterozygous
for targeted disruption of the ETB gene with mice homozygous for the piebald (s)
mutation of the ETB gene (ETBs/s). F1 ETB-/s and ETB+/s progeny share an
identical genetic background but have ETB levels that are approximately (1)/(8)
and (5)/(8), respectively, of wild-type mice (ETB+/+). BP in ETB-/s mice was
significantly higher, by approximately 20 mmHg, than that in ETB+/s or ETB+/+
mice. Immunoreactive ET-1 concentration in plasma as well as respiratory
parameters was not different between ETB-/s and ETB+/s mice. A selective ETB
antagonist, BQ-788, increased BP in ETB+/s and ETB+/+ but not in ETB-/s mice.
Pretreatment with indomethacin, but not with NG-monomethyl-L-arginine, can
attenuate the observed pressor response to BQ-788. The selective ETA antagonist
BQ-123 did not ameliorate the increased BP in ETB-/s mice. Moreover, BP in mice
heterozygous for targeted disruption of the ETA gene was not different from that
in wild-type controls. These results suggest that endogenous ET elicits a
depressor effect through ETB under basal conditions, in part through tonic
production of prostaglandins, and not through secondary mechanisms involving
respiratory control or clearance of circulating ET.
PMID- 10198388
TI - Interstrain differences in activity pattern, pineal function, and SCN melatonin
receptor density of rats.
AB - We investigated the possibility that strain-dependent differences in the diurnal
pattern of wheel running activity rhythms are also reflected in the melatonin
profiles. The inbred rat strains ACI/Ztm, BH/Ztm, and LEW/Ztm. LEW were examined
for diurnal [12:12-h light-dark (LD)] wheel running activity, urinary 6
sulphatoxymelatonin (aMT6s) excretion, melatonin concentrations of plasma and
pineal glands, and melatonin receptor density in the suprachiasmatic nuclei
(SCN). ACI rats displayed unimodal activity patterns with a high level of
activity, whereas BH and LEW rats showed multimodal activity patterns with
ultradian components and reduced activity levels. In contrast, the individual
daily profiles of aMT6s excretion and mean melatonin synthesis followed a
unimodal time pattern in all three strains, suggesting that different output
pathways of the SCN are responsible for the temporal organization of locomotor
activity and pineal melatonin synthesis. In addition, melatonin synthesis at
night and SCN melatonin receptor density at day were significantly higher in BH
and LEW rats than in ACI rats. These results support the hypothesis of a long
term stimulating effect of melatonin on its own receptor density in the SCN.
PMID- 10198390
TI - Core temperature and sweating onset in humans acclimated to heat given at a fixed
daily time.
AB - The thermoregulatory functions of rats acclimated to heat given daily at a fixed
time are altered, especially during the period in which they were previously
exposed to heat. In this study, we investigated the existence of similar
phenomena in humans. Volunteers were exposed to an ambient temperature (Ta) of 46
degrees C and a relative humidity of 20% for 4 h (1400-1800) for 9-10 consecutive
days. In the first experiment, the rectal temperatures (Tre) of six subjects were
measured over 24 h at a Ta of 27 degrees C with and without heat acclimation.
Heat acclimation significantly lowered Tre only between 1400 and 1800. In the
second experiment, six subjects rested in a chair at a Ta of 28 degrees C and a
relative humidity of 40% with both legs immersed in warm water (42 degrees C) for
30 min. The Tre and sweating rates at the forearm and chest were measured.
Measurements were made in the morning (0900-1100) and afternoon (1500-1700) on
the same day before and after heat acclimation. Heat acclimation shortened the
sweating latency and decreased the threshold Tre for sweating. However, these
changes were significant only in the afternoon. The results suggest that repeated
heat exposure in humans, limited to a fixed time daily, alters the core
temperature level and thermoregulatory function, especially during the period in
which the subjects had previously been exposed to heat.
PMID- 10198389
TI - Contribution of endogenous carbon monoxide to regulation of diameter in
resistance vessels.
AB - Endogenous carbon monoxide was proposed to subserve vasodepressor functions. If
so, inhibition of heme oxygenase may be expected to promote vascular contraction.
This hypothesis was examined in large and small arteries and in isolated first
order gracilis muscle arterioles of rat. The heme oxygenase inhibitors chromium
mesoporphyrin (CrMP) and cobalt protoporphyrin (0.175-102 micromol/l) decreased
the diameter of pressurized (80 mmHg) gracilis muscle arterioles, whereas
magnesium protoporphyrin, a weak heme oxygenase inhibitor, did not. CrMP also
elicited development of isometric tension in the muscular branch of the femoral
artery but not in the aorta or femoral artery. Arteriolar constrictor responses
to CrMP varied in relation to the intravascular pressure, were blunted in
preparations exposed to exogenous carbon monoxide (100 micromol/l), and were
unaffected by an endothelin receptor antagonist. Importantly, CrMP amplified the
constrictor response to increases of pressure in gracilis arterioles.
Accordingly, the constrictor effect of heme oxygenase inhibitors is attributable
to magnification of myogenic tone due to withdrawal of a vasodilatory mechanism
mediated by endogenous carbon monoxide. The study suggests that the vascular
carbon monoxide system plays a role in the regulation of basal tone in resistance
vessels.
PMID- 10198391
TI - Cardiac inotropic, chronotropic, and dromotropic actions of subretrofacial
neurons of cat RVLM.
AB - The cardiac actions of microinjecting sodium glutamate (0.5-2 nmol) among
sympathetic premotor neurons of the subretrofacial nucleus in the rostral
ventrolateral medulla (RVLM) were studied in chloralose-anesthetized cats after
bilateral vagotomy, sinoaortic denervation, adrenalectomy, and alpha1-receptor
blockade. Glutamate microinjections increased heart rate by 25.9 +/- 1.8
beats/min (17. 5%), systolic rate of rise in left ventricular pressure (LVdP/dt)
by 1,443 +/- 110 mmHg/s (119%), and arterial blood pressure by 26.9 +/- 1.7 mmHg
(50%), whereas they shortened the electrocardiogram P-R interval in 85 of 103
cases by 7.5 +/- 1.2 ms (11.4%), triggering junctional rhythms on five occasions.
The increase in LVdP/dt usually led the rise in blood pressure, and its magnitude
greatly exceeded any increase attributable to changes in heart rate, diastolic
filling, or afterload. Right-sided microinjections caused significantly greater
tachycardias than did left-sided microinjections, but only left-sided
microinjections triggered junctional rhythms (5 of 52 vs. 0 of 51; P < 0.05),
whereas microinjections on either side raised LVdP/dt equally. Subretrofacial
neurons thus drive positive chronotropic, inotropic, and dromotropic actions via
the cardiac sympathetic nerves, whereas subsets among them preferentially control
different aspects of cardiac function.
PMID- 10198392
TI - Influence of right atrial pressure on the cardiac pacemaker response to vagal
stimulation.
AB - We have recently shown that the intrinsic rate response to an increase in right
atrial pressure is augmented when cardiac muscarinic receptors are activated.
This present study examines the cardiac pacemaker response to vagal stimulation
at different values of right atrial pressure in isolated rat right atrium and in
the rabbit heart in situ. In the rat atrium, when pressure was raised in steps
from 2 to 10 mmHg, there was a progressive reduction in the response to vagal
stimulation [40.5 +/- 7.2% reduction (mean +/- SE) at 8 mmHg, P < 0.01], which
was independent of the level of vagal bradycardia, that persisted in the presence
of the beta-adrenergic agonist isoproterenol. In barbiturate-anesthetized rabbits
with cervical vagi cut and beta-adrenergic blockade, raising right atrial
pressure approximately 2.5 mmHg by blood volume expansion reduced the bradycardia
elicited by electrical stimulation of the peripheral end of the right vagus nerve
(9.1 +/- 1.1% reduction, P < 0.0001). These results demonstrate that vagal
bradycardia is modulated by the level of right atrial pressure and suggest that
normally right atrial pressure may interact with cardiac vagal activity in the
control of heart rate.
PMID- 10198393
TI - Effects of adrenomedullin and PAMP on adrenal catecholamine release in dogs.
AB - We examined the effects of proadrenomedullin-derived peptides on the release of
adrenal catecholamines in response to cholinergic stimuli in pentobarbital sodium
anesthetized dogs. Drugs were administered into the adrenal gland through the
phrenicoabdominal artery. Splanchnic nerve stimulation (1, 2, and 3 Hz) and ACh
injection (0.75, 1.5, and 3 microgram) produced frequency- or dose-dependent
increases in adrenal catecholamine output. These responses were unaffected by
infusion of adrenomedullin (1, 3, and 10 ng. kg-1. min-1) or its selective
antagonist adrenomedullin-(22-52) (5, 15, and 50 ng. kg-1. min-1).
Proadrenomedullin NH2-terminal 20 peptide (PAMP; 5, 15, and 50 ng. kg-1. min-1)
suppressed both the splanchnic nerve stimulation- and ACh-induced increases in
catecholamine output in a dose-dependent manner. PAMP also suppressed the
catecholamine release responses to the nicotinic agonist 1, 1-dimethyl-4
phenylpiperazinium (0.5, 1, and 2 microgram) and to muscarine (0.5, 1, and 2
microgram), although the muscarine-induced response was relatively resistant to
PAMP. These results suggest that PAMP, but not adrenomedullin, can act as an
inhibitory regulator of adrenal catecholamine release in vivo.
PMID- 10198394
TI - Inhibition of prostaglandin and nitric oxide synthesis prevents cortisol-induced
renal vasodilatation in sheep.
AB - Glucocorticoids increase renal blood flow (RBF) and glomerular filtration rate in
many species, but the mechanisms involved are unclear. We investigated whether
cortisol-induced renal vasodilatation in conscious sheep depends on interactions
with prostaglandins or angiotensin II. Intravenous infusion of cortisol (5 mg/h)
for 5 h increased renal conductance (RC) by 1.06 +/- 0.24 ml. min-1. mmHg-1 more
than vehicle. During intrarenal infusion of indomethacin (0.25 mg. kg-1. h-1),
the cortisol-induced increase in RC (0.28 +/- 0.21 ml. min-1. mmHg-1) was
significantly reduced. The cortisol-induced rise in RBF (103 +/- 17 ml/min) was
not significantly reduced by indomethacin treatment (76 +/- 9 ml/min). Combined
intrarenal infusion of indomethacin (0.25 mg. kg-1. h-1) with Nomega-nitro-L
arginine (2.0 mg. kg-1. h-1), a nitric oxide synthase inhibitor, abolished the
cortisol-induced increases in both RC and RBF. Inhibition of angiotensin II
synthesis with intravenous captopril (40 mg/h) blocked the renal vasoconstrictor
action of angiotensin I but did not inhibit the cortisol-induced increases in RBF
and RC. This study provides evidence that nitric oxide and prostaglandins play a
role in cortisol-induced renal vasodilatation but indicates that this response is
independent of an interaction with angiotensin.
PMID- 10198395
TI - Somnogenic relationships between tumor necrosis factor and interleukin-1.
AB - Both tumor necrosis factor (TNF) and interleukin (IL)-1 are somnogenic cytokines.
They also induce each other's production and both induce nuclear factor kappa B
activation, which in turn enhances IL-1 and TNF transcription. We hypothesized
that TNF and IL-1 could influence each other's somnogenic actions. To test this
hypothesis, we determined the effects of blocking both endogenous TNF and IL-1 on
spontaneous sleep and on sleep rebound after sleep deprivation in rabbits.
Furthermore, the effects of inhibition of TNF on IL-1-induced sleep and the
effects of blocking IL-1 on TNF-induced sleep were determined. A TNF receptor
fragment (TNFRF), as a TNF inhibitor, and an IL-1 receptor fragment (IL-1RF), as
an IL-1 inhibitor, were used. Intracerebroventricular injection of a combination
of the TNFRF plus the IL-1RF significantly reduced spontaneous non-rapid eye
movement sleep by 87 min over a 22-h recording period. Pretreatment of rabbits
with the combination of TNFRF and IL-1RF also significantly attenuated sleep
rebound after sleep deprivation. Furthermore, the TNFRF significantly attenuated
IL-1-induced sleep but not fever. Finally, the IL-1RF blocked TNF-induced sleep
responses but not fever. Results indicate that TNF and IL-1 cooperate to regulate
physiological sleep.
PMID- 10198396
TI - Cholinergic systems in the nucleus of the solitary tract of rats.
AB - The pharmacological and physiological properties of excitatory amino acid and ACh
systems in the nucleus of the solitary tract (NTS) were studied in slices of rat
brain stem by extracellular and intracellular recordings from neurons activated
by solitary tract (ST) stimulation. These neurons were characterized as having
several long dendrites with multiple varicosities. Synaptic activation of the
medial NTS (mNTS) neurons by ST stimulation was mediated by non-N-methyl-D
aspartate (NMDA) glutamate (Glu) receptors, because the excitation was blocked by
6-cyano-7-nitro-quinoxaline-2,3-dione but not by NMDA, nicotinic, or muscarinic
antagonists. Identified mNTS neurons were excited by iontophoresis of both Glu
and ACh. The most sensitive region of the cell was on the dendrites approximately
100 micrometer from the cell body for both putative neurotransmitters. Nicotinic
and/or muscarinic excitatory ACh responses were detected on the mNTS neurons. Our
observations suggest that both types of ACh receptors may contribute to the
attenuation of the baroreceptor reflex, but the functional correlation of this
receptor profile remains to be determined.
PMID- 10198397
TI - Effects of granulocyte colony-stimulating factor on night sleep in humans.
AB - Numerous animal studies suggest that cytokines such as interleukin-1beta (IL
1beta) and tumor necrosis factor-alpha (TNF-alpha) mediate increased sleep amount
and intensity observed during infection and are, moreover, involved in
physiological sleep regulation. In humans the role of cytokines in sleep-wake
regulation is largely unknown. In a single-blind, placebo-controlled study, we
investigated the effects of granulocyte colony-stimulating factor (G-CSF, 300
microgram sc) on the plasma levels of cytokines, soluble cytokine receptors, and
hormones as well as on night sleep. G-CSF did not affect rectal temperature or
the plasma levels of cortisol and growth hormone but did induce increases in the
plasma levels of IL-1 receptor antagonist and both soluble TNF receptors within 2
h after injection. In parallel, the amount of slow-wave sleep and
electroencephalographic delta power were reduced, indicating a lowered sleep
intensity. We conclude that G-CSF suppresses sleep intensity via increased
circulating amounts of endogenous antagonists of IL-1beta and TNF-alpha activity,
suggesting that these cytokines are involved in human sleep regulation.
PMID- 10198398
TI - A rapid feedback signal is not always necessary for termination of a drinking
bout.
AB - When a pig is deprived of drinking water, a deficit of body water develops that
is corrected when the pig drinks to satiation. If food is available during the
deprivation, the stimulus to drinking is plasma hyperosmolality. Because of the
delay in correction of plasma hyperosmolality as ingested water is slowly
absorbed, it has been thought that a rapid inhibitory signal from the digestive
tract is necessary to prevent overdrinking. This concept was tested by measuring
changes in plasma osmolality before and during drinking after such deprivation
and also after infusion of hypertonic saline. As drinking began, there was a
rapid fall of plasma osmolality to levels insufficient to drive drinking by the
time drinking ended. This fall of plasma hyperosmolality to subthreshold levels
while the pig is drinking seems to make a rapid inhibitory control signal from
the digestive tract unnecessary to terminate the drinking bout under these
conditions.
PMID- 10198399
TI - Glucose regulation of the IGF response system in chondrocytes: induction of an
IGF-I-resistant state.
AB - Nonresponsiveness to the growth-stimulatory actions of insulin-like growth factor
(IGF)-I in chondrocytes has been reported in a number of disease states
associated with impaired glucose metabolism. Primary rabbit chondrocytes were
investigated for changes in their IGF response system [type-I IGF receptor and
IGF-binding protein (IGFBP) expression] and in their ability to mount a synthetic
response to IGF-I [as 35S-labeled proteoglycan ([35S]PG) production] in media
containing varying ambient glucose concentrations. Whereas basal [35S]PG
synthetic rate was unaffected by glucose concentration, synthetic responsiveness
to IGF-I was lost in media containing <5 mmol/l glucose or in media containing a
"diabetic" glucose concentration (25 mmol/l). IGFBP expression, as measured by
Northern analysis of mRNA levels and Western ligand blotting of secreted protein
levels, was not significantly altered in the different glucose media, nor were
there any differences in the cell surface localization of IGFBPs as assessed by
affinity cross-linking with 125I-labeled IGF-I, suggesting that IGFBPs do not
induce the IGF-I resistance. The nonresponsiveness to IGF-I in reduced glucose
occurred with 25-50% reductions in steady-state levels of IGF type-I receptor
mRNA and protein. A significant correlation between IGF receptor mRNA level and
synthetic response to IGF-I was observed between 0 and 10 mmol/l glucose
concentrations, suggesting that the loss of responsiveness in reduced glucose is
manifested at the level of transcription and/or receptor mRNA stability. In
contrast, nonresponsiveness to IGF-I in chondrocytes in diabetic glucose
concentrations occurred without changes in receptor mRNA and protein levels,
suggesting that IGF-I resistance was due to post-ligand-binding receptor defects.
It is proposed that IGF-I resistance in chondrocytes subjected to inappropriate
glucose levels may constitute an important pathogenic mechanism in degenerative
cartilage disorders.
PMID- 10198400
TI - Conjugated linoleic acid rapidly reduces body fat content in mice without
affecting energy intake.
AB - Recent reports have demonstrated that conjugated linoleic acid (CLA) has effects
on body fat accumulation. In our previous work, CLA reduced body fat accumulation
in mice fed either a high-fat or low-fat diet. Although CLA feeding reduced
energy intake, the results suggested that some of the metabolic effects were not
a consequence of the reduced food intake. We therefore undertook a study to
determine a dose of CLA that would have effects on body composition without
affecting energy intake. Five doses of CLA (0.0, 0.25, 0.50, 0.75, and 1.0% by
weight) were studied in AKR/J male mice (n = 12/group; age, 39 days) maintained
on a high-fat diet (%fat 45 kcal). Energy intake was not suppressed by any CLA
dose. Body fat was significantly lower in the 0.50, 0.75, and 1.0% CLA groups
compared with controls. The retroperitoneal depot was most sensitive to the
effects of CLA, whereas the epididymal depot was relatively resistant. Higher
doses of CLA also significantly increased carcass protein content. A time-course
study of the effects of 1% CLA on body composition showed reductions in fat pad
weights within 2 wk and continued throughout 12 wk of CLA feeding. In conclusion,
CLA feeding produces a rapid, marked decrease in fat accumulation, and an
increase in protein accumulation, at relatively low doses without any major
effects on food intake.
PMID- 10198401
TI - Distribution of Fos immunoreactivity in rat brain after sodium consumption
induced by peritoneal dialysis.
AB - Fos immunoreactivity was used to map the neuronal population groups activated
after sodium ingestion induced by peritoneal dialysis (PD) in rats. Oxytocin
immunoreactivity in combination with Fos immunoreactivity was also analyzed to
evaluate whether the oxytocinergic neurons of the paraventricular nucleus of the
hypothalamus (PVN) are activated during the satiety process of sodium appetite.
Sodium ingestion stimulated by PD produced Fos immunoreactivity within defined
cells groups of the lamina terminalis and hindbrain areas such us the nucleus of
the solitary tract, area postrema, and lateral parabrachial nucleus. On the other
hand, particular parvocellular and magnocellular oxytocinergic subdivisions of
the PVN and supraoptic nucleus were double labeled after PD-induced sodium
consumption. Approximately 27 and 2.1%, respectively, of the activated
dorsomedial cap and parvocellular posterior subnuclei of the PVN, which project
to the hindbrain, were oxytocinergic. Our data indicate that specific neuronal
groups are activated during the satiety process of sodium appetite, suggesting
they may form a circuit subserving sodium balance regulation. They also support a
functional role for the oxytocinergic neurons in this circuit.
PMID- 10198402
TI - How dolphins use their blubber to avoid heat stress during encounters with warm
water.
AB - Dolphins have been observed swimming in inshore tropical waters as warm as 36-38
degrees C. A simple protocol that mimicked the thermal conditions encountered by
a dolphin moving from cool pelagic to warm inshore water was used to determine
how dolphins avoid hyperthermia in water temperatures (Tw) at and above their
normal core temperature (Tc). Tw (2 sites), rectal temperature (Tre; 3 depths),
and skin temperature (Tsk; 7 sites) and rate of heat flow (4-5 sites) between the
skin and the environment were measured while the dolphin rested in a chamber
during a 30-min baseline and 40-60 min while water was warmed at approximately
0.43 degrees C/min until temperatures of 34-36 degrees C were attained. Instead
of the expected increase, Tre consistently showed declines during the warming
ramp, sometimes by amounts that were remarkable both in their magnitude (1.35
degrees C) and rapidity (8-15 min). The reduction in Tre occurred even while heat
loss to the environment was prevented by continued controlled warming of the
water that kept Tw slightly above Tsk and while metabolic heat production alone
should have added 1.6-2 degrees C/h to the Tc. This reduction in Tc could only be
due to a massive redistribution of heat from the core to the blubber layer.
PMID- 10198403
TI - Effects of square-wave and simulated natural light-dark cycles on hamster
circadian rhythms.
AB - Circadian rhythms of activity (Act) and body temperature (Tb) were recorded from
male Syrian hamsters under square-wave (LDSq) and simulated natural (LDSN, with
dawn and dusk transitions) light-dark cycles. Light intensity and data sampling
were under the synchronized control of a laboratory computer. Changes in reactive
and predictive onsets and offsets for the circadian rhythms of Act and Tb were
examined in both lighting conditions. The reactive Act onset occurred 1.1 h
earlier (P < 0.01) in LDSN than in LDSq and had a longer alpha-period (1.7 h; P <
0.05). The reactive Tb onset was 0.7 h earlier (P < 0.01) in LDSN. In LDSN, the
predictive Act onset advanced by 0.3 h (P < 0.05), whereas the Tb predictive
onset remained the same as in LDSq. The phase angle difference between Act and Tb
predictive onsets decreased by 0.9 h (P < 0.05) in LDSN, but the offsets of both
measures remained unchanged. In this study, animals exhibited different circadian
entrainment characteristics under LDSq and LDSN, suggesting that gradual and
abrupt transitions between light and dark may provide different temporal cues.
PMID- 10198404
TI - Does gender influence the strength and mechanisms of the muscle metaboreflex
during dynamic exercise in dogs?
AB - Ischemia of active skeletal muscle stimulates neuronal afferents within the
muscle, which elicits a reflex increase in sympathetic nerve activity, systemic
arterial pressure (SAP), and heart rate (HR), termed the muscle metaboreflex. We
retrospectively investigated whether gender influences the activation of the
muscle metaboreflex and the primary mechanisms used by this reflex, augmentation
of cardiac output (CO) and peripheral vasoconstriction, using 15 female and 13
male chronically instrumented dogs exercising on a treadmill (3.2 km/h, 0%
grade). Metaboreflex activation was achieved via progressive partial vascular
occlusion of the terminal aorta during exercise. In both females and males,
hindlimb ischemia elicited similar substantial increases in SAP (56.1 +/- 3.0 and
55.1 +/- 4.2 mmHg, respectively), HR (25.8 +/- 4.8 and 33.9 +/- 2.8 beats/min,
respectively), and CO (1.39 +/- 0.3 and 1.64 +/- 0.2 liters, respectively) and a
similar substantial decrease in renal vascular conductance (RVC; 42.7 +/- 4.9 and
42.9 +/- 5.3%, respectively). Both groups also demonstrated similar metaboreflex
thresholds and sensitivities of SAP, HR, CO, and RVC. We conclude that the
strength and mechanisms mediating the metaboreflex responses during dynamic
exercise in dogs are not affected by gender.
PMID- 10198405
TI - Tonic drive to sympathetic premotor neurons of rostral ventrolateral medulla from
caudal pressor area neurons.
AB - The responses of sympathetic premotor neurons in the rostral ventrolateral
medulla (RVLM) to activation or inactivation of neurons in the caudal pressor
area (CPA) were studied in urethan-anesthetized rats. Extracellular recordings
were made from 32 barosensitive single units in the RVLM, of which 26 were
antidromically activated from the cervical cord. Unilateral microinjections of L
glutamate (0.5-5 nmol) into the CPA increased firing in 13 of 14 premotor neurons
by 90 +/- 30% while raising blood pressure. Both ipsilateral and contralateral
injections were effective. Unilateral or bilateral inhibition of CPA neuron
activity by microinjecting glycine (5-200 nmol/side) lowered blood pressure,
while it reduced firing in 9 of 10 and 16 of 17 premotor neurons, respectively,
by 45 +/- 9 and 39 +/- 6%. A significant proportion of tonic activity in RVLM
sympathetic premotor neurons is thus driven, directly or indirectly, by neurons
in the CPA.
PMID- 10198406
TI - Altered airway and cardiac responses in mice lacking G protein-coupled receptor
kinase 3.
AB - Contraction and relaxation of airway smooth muscles is mediated, in part, by G
protein-coupled receptors (GPCRs) and dysfunction of these receptors has been
implicated in asthma. Phosphorylation of GPCRs, by G protein-coupled receptor
kinase (GRK), is an important mechanism involved in the dampening of GPCR
signaling. To determine whether this mechanism might play a role in airway smooth
muscle physiology, we examined the airway pressure time index and heart rate (HR)
responses to intravenous administration of the cholinergic agonist methacholine
(MCh) in genetically altered mice lacking one copy of GRK2 (GRK2 +/-), homozygous
GRK3 knockout (GRK3 -/-), and wild-type littermates. (GRK2 -/- mice die in
utero.) GRK3 -/- mice demonstrated a significant enhancement in the airway
response to 100 and 250 microgram/kg doses of MCh compared with wild-type and
GRK2 +/- mice. GRK3 -/- mice also displayed an enhanced sensitivity of the airway
smooth muscle response to MCh. In addition, GRK3 -/- mice displayed an altered HR
recovery from MCh-induced bradycardia. Although direct stimulation of cardiac
muscarinic receptors measured as vagal stimulation-induced bradycardia was
similar in GRK3 -/- and wild-type mice, the baroreflex increase in HR associated
with sodium nitroprusside-induced hypotension was significantly greater in GRK3
/- than wild-type mice. Therefore, these data demonstrate that in the mouse, GRK3
may be involved in modulating the cholinergic response of airway smooth muscle
and in regulating the chronotropic component of the baroreceptor reflex.
PMID- 10198407
TI - Molecular regulation of nephron endowment.
AB - Recent data suggests that the number of nephrons in normal adult human kidneys
ranges from approximately 300,000 to more than 1 million. There is increasing
evidence that reduced nephron number, either inherited or acquired, is associated
with the development of essential hypertension, chronic renal failure, renal
disease in transitional indigenous populations, and possibly the long-term
success of renal allografts. Three processes ultimately govern the number of
nephrons formed during the development of the permanent kidney (metanephros):
branching of the ureteric duct in the metanephric mesenchyme; condensation of
mesenchymal cells at the tips of the ureteric branches; and conversion of the
mesenchymal condensates into epithelium. This epithelium then grows and
differentiates to form nephrons. In recent years, we have learned a great deal
about the molecular regulation of these three central processes and hence the
molecular regulation of nephron endowment. Data has come from studies on cell
lines, isolated ureteric duct epithelial cells, isolated metanephric mesenchyme,
and whole metanephric organ culture, as well as from studies of heterozygous and
homozygous null mutant mice. With accurate and precise methods now available for
estimating the total number of nephrons in kidneys, more advances in our
understanding of the molecular regulation of nephron endowment can be expected in
the near future.
PMID- 10198408
TI - Developmental expression of aquaporin 1 in the rat renal vasculature.
AB - Aquaporin 1 (AQP-1) is a water channel protein that is constitutively expressed
in renal proximal tubule and descending thin limb cells as well as in endothelial
cells of the descending vasa recta. Studies in the developing rat kidney have
demonstrated that AQP-1 is expressed in renal tubules before birth. However,
nothing is known about the expression of AQP-1 in the renal vasculature during
kidney development. The purpose of this study was to establish the distribution
of AQP-1 in the renal vasculature of the developing rat kidney and follow the
differentiation of the vascular system during kidney development. Kidneys from 16
, 17-, 18-, and 20-day-old fetuses and 1-, 4-, 7-, 14-, 21-, and 28-day-old pups
were preserved and processed for immunohistochemical studies using a preembedding
immunoperoxidase procedure. AQP-1 immunoreactivity was detected using affinity
purified rabbit polyclonal antibodies to AQP-1. AQP-1 was expressed throughout
the arterial portion of the renal vasculature of the fetal and neonatal kidney
from gestational age 17 days to 1 wk after birth. AQP-1 immunoreactivity
gradually disappeared from the renal vasculature between 1 and 2 wk of age and
remained only in the descending vasa recta. In contrast, AQP-1 immunoreactivity
was not observed in lymphatic vessels until 3 wk of age and persisted in the
adult kidney. AQP-1 was also expressed in a population of interstitial cells in
the terminal part of the renal papilla at 3 wk of age as well as in the adult
kidney. The transient expression of AQP-1 in the arterial portion of the renal
vasculature in the developing rat kidney suggests that AQP-1 is important for
fluid equilibrium and/or drainage in the developing kidney or, alternatively,
plays a role in the regulation of growth and/or branching of the vascular tree
during kidney development.
PMID- 10198409
TI - Postnatal development of carbonic anhydrase IV expression in rabbit kidney.
AB - Carbonic anhydrase (CA) IV activity facilitates renal acidification by catalyzing
the dehydration of luminal carbonic acid. CA IV has been localized to the
proximal tubules and medullary collecting ducts. Maturation of CA IV expression
has been considered to be important in the development of renal acid excretion.
The purpose of the present study was to determine the maturational expression of
CA IV in rabbit kidney. A guinea pig polyclonal antibody to purified rabbit lung
microsomal membrane CA IV was generated. Immunoblotting of membrane proteins
after peptide-N-glycosidase F treatment revealed two N-glycosylation sites and
reduction in size from approximately 52 to 35 kDa; there appeared to be heavier
glycosylation in the medulla. In membrane and total proteins from the kidney
cortex, CA IV was 15-30% of the adult level during the first 2 wk of life but
increased to mature levels by 5 wk of age. The maturational pattern in the cortex
was confirmed by measuring SDS-resistant CA hydratase activity. In the medulla,
both membrane and total proteins were generally less than one-fourth of the adult
level of CA IV during the first 2 wk of life before reaching mature levels by 5
wk of age. Immunohistochemistry showed staining in proximal tubules (apical >
basolateral), with maximal label in the S2 segment. CA IV also appeared on the
apical membranes of a minority cell type of the cortical collecting duct,
presumably the alpha-intercalated cell. Several labeled cells also appeared to be
the process of being extruded from medullary collecting ducts of 1- to 2-wk
rabbits. The antibody did not reliably detect medullary CA IV expression in
sections from mature rabbits. These studies indicate that there is a substantial
postnatal increase in expression of CA IV in the maturing kidney in both the
cortex and medulla. The disappearance of intercalated cells in the maturing
rabbit medullary collecting duct may be part of a normal renal developmental
program as previously reported [J. Kim, J.-H. Cha, C. C. Tisher, and K. M.
Madsen. Am. J. Physiol. 270 (Renal Fluid Electrolyte Physiol. 39): F575-F592,
1996]. It is likely that the maturation of CA IV expression contributes to the
increase in renal acidification observed early in postnatal life.
PMID- 10198410
TI - Partial characterization of apoptotic factor in Alzheimer plasma.
AB - We have previously demonstrated that a plasma natriuretic factor is present in
Alzheimer's disease (AD), but not in multi-infarct dementia (MID) or normal
controls (C). We postulated that the natriuretic factor might induce the
increased cytosolic calcium reported in AD by inhibiting the sodium-calcium
antiporter, thereby activating the apoptotic pathway. To test for a factor in AD
plasma that induces apoptosis, we exposed nonconfluent cultured LLC-PK1 cells to
plasma from AD, MID, and C for 2 h and performed a terminal transferase-dUTP-nick
end labeling (TUNEL) assay. The plasma from AD increased apoptosis nearly
fourfold compared with MID and C. The effect was dose dependent and the peak
effect was attained after a 2-h exposure. Additionally, apoptotic morphology was
detected by electron microscopy, and internucleosomal DNA cleavage was found. We
inhibited apoptosis by removing calcium from the medium, inhibiting protein
synthesis with cycloheximide, alternately boiling or freezing and thawing the
plasma, and digesting a partially purified fraction with trypsin. Heating AD
plasma to 56 degrees C did not deactivate the apoptotic factor. These results
demonstrate the presence of an apoptotic factor in the plasma of patients with
AD.
PMID- 10198411
TI - Agonist-induced translocation of Gq/11alpha immunoreactivity directly from plasma
membrane in MDCK cells.
AB - Both Gsalpha and Gqalpha are palmitoylated and both can move from a crude
membrane fraction to a soluble fraction in response to stimulation with agonists.
This response may be mediated through depalmitoylation. Previous studies have not
demonstrated that endogenous guanine nucleotide-binding regulatory protein (G
protein) alpha-subunits are released directly from the plasma membrane. We have
examined the effect of agonist stimulation on the location of Gq/11alpha
immunoreactivity in Madin-Darby canine kidney (MDCK) cells. Bradykinin (BK; 0.1
microM) caused Gq/11alpha, but not Gialpha, to rapidly translocate from purified
plasma membranes to the supernatant. AlF and GTP also caused translocation of
Gq/11alpha immunoreactivity from purified plasma membranes. BK caused
translocation of Gq/11alpha immunoreactivity in intact cells from the basal and
lateral plasma membranes to an intracellular compartment as assessed by confocal
microscopy. Thus Gq/11alpha is released directly from the plasma membrane to an
intracellular location in response to activation by an agonist and direct
activation of G proteins. G protein translocation may be a mechanism for
desensitization or for signaling specificity.
PMID- 10198412
TI - Modulation of renal tubular cell function by RGS3.
AB - The recently discovered family of regulators of G protein signaling (RGS)
accelerates the intrinsic GTPase activity of certain Galpha subunits, thereby
terminating G protein signaling. Particularly high mRNA levels of one family
member, RGS3, are found in the adult kidney. To establish the temporal and
spatial renal expression pattern of RGS3, a polyclonal antiserum was raised
against the COOH terminus of RGS3. Staining of mouse renal tissue at different
gestational stages revealed high levels of RGS3 within the developing and mature
tubular epithelial cells. We tested whether RGS3 can modulate tubular migration,
an important aspect of tubular development, in response to G protein-mediated
signaling. Several mouse intermedullary collecting duct (mIMCD-3) cell lines were
generated that expressed RGS3 under the control of an inducible promoter.
Lysophosphatidic acid (LPA) is a potent chemoattractant that mediates its effects
through heterotrimeric G proteins. We found that induction of RGS3 significantly
reduced LPA-mediated cell migration in RGS3-expressing mIMCD-3 clones, whereas
chemotaxis induced by hepatocyte growth factor remained unaffected by RGS3. Our
findings suggest that RGS3 modulates tubular functions during renal development
and in the adult kidney.
PMID- 10198413
TI - Ischemia activates actin depolymerizing factor: role in proximal tubule
microvillar actin alterations.
AB - Apical membrane of renal proximal tubule cells is extremely sensitive to
ischemia, with structural alterations occurring within 5 min. These changes are
felt secondary to actin cytoskeletal disruption, yet the mechanism responsible is
unknown. Actin depolymerizing factor (ADF), a 19-kDa actin-binding protein, has
recently been shown to play an important role in regulation of actin filament
dynamics. Because ADF is known to mediate pH-dependent F-actin binding,
depolymerization, and severing, and because ADF activation occurs by
dephosphorylation, we questioned whether ADF played a role in microvilli
microfilament disruption during ischemia. To test our hypothesis, we induced
renal ischemia in the rat with the clamp model. Initial immunofluorescence and
Western blot studies on cortical tissue documented the presence of ADF in
proximal tubule cells. Under physiological conditions, ADF was distributed
homogeneously throughout the cytoplasm, primarily in the Triton X-100-soluble
fraction, and both phosphorylated (pADF) and nonphosphorylated forms were
identified. During ischemia, marked alterations occurred. Intraluminal
vesicle/bleb structures contained extremely high concentrations of ADF along with
G-actin, but not F-actin. Western blot showed a rapidly occurring duration
dependent dephosphorylation of ADF. At 0-30 min of ischemia, total ADF levels
were unchanged, whereas pADF decreased significantly to 72% and 19% of control
levels, at 5 and 15 min, respectively. Urine collected under physiological
conditions did not contain ADF or actin, whereas urine collected after 30 min of
ischemia contained both ADF and actin. Reperfusion was associated with
normalization of cellular pADF levels, pADF intracellular distribution, and
repair of apical microvilli. These data suggest that activation of ADF during
ischemia via dephosphorylation is, in part, responsible for apical actin
disruption resulting in microvillar destruction and formation of intraluminal
vesicles.
PMID- 10198414
TI - Localization of rat CLC-K2 chloride channel mRNA in the kidney.
AB - To gain insight into the physiological role of a kidney-specific chloride
channel, CLC-K2, the exact intrarenal localization was determined by in situ
hybridization. In contrast to the inner medullary localization of CLC-K1, the
signal of CLC-K2 in our in situ hybridization study was highly evident in the
superficial cortex, moderate in the outer medulla, and absent in the inner
medulla. To identify the nephron segments where CLC-K2 mRNA was expressed, we
performed in situ hybridization of CLC-K2 and immunohistochemistry of marker
proteins (Na+/Ca2+ exchanger, Na+-Cl- cotransporter, aquaporin-2 water channel,
and Tamm-Horsfall glycoprotein) in sequential sections of a rat kidney. Among the
tubules of the superficial cortex, CLC-K2 mRNA was highly expressed in the distal
convoluted tubules, connecting tubules, and cortical collecting ducts. The
expression of CLC-K2 in the outer and inner medullary collecting ducts was almost
absent. In contrast, a moderate signal of CLC-K2 mRNA was observed in the
medullary thick ascending limb of Henle's loop, but the signal in the cortical
thick ascending limb of Henle's loop was low. These results clearly demonstrated
that CLC-K2 was not colocalized with CLC-K1 and that its localization along the
nephron segments was relatively broad compared with that of CLC-K1.
PMID- 10198415
TI - Vasopressin regulates apical targeting of aquaporin-2 but not of UT1 urea
transporter in renal collecting duct.
AB - In the renal inner medullary collecting duct (IMCD), vasopressin regulates two
key transporters, namely aquaporin-2 (AQP2) and the vasopressin-regulated urea
transporter (VRUT). Both are present in intracellular vesicles as well as the
apical plasma membrane. Short-term regulation of AQP2 has been demonstrated to
occur by vasopressin-induced trafficking of AQP2-containing vesicles to the
apical plasma membrane. Here, we have carried out studies to determine whether
short-term regulation of VRUT occurs by a similar process. Cell surface labeling
with NHS-LC-biotin in rat IMCD suspensions revealed that vasopressin causes a
dose-dependent increase in the amount of AQP2 labeled at the cell surface,
whereas VRUT labeled at the cell surface did not increase in response to
vasopressin. Immunoperoxidase labeling of inner medullary thin sections from
Brattleboro rats treated with 1-desamino-8-D-arginine vasopressin (DDAVP) for 20
min revealed dramatic translocation of AQP2 to the apical region of the cell,
with no change in the cellular distribution of VRUT. In addition, differential
centrifugation of inner medullary homogenates from Brattleboro rats treated with
DDAVP for 60 min revealed a marked depletion of AQP2 from the low-density
membrane fraction (enriched in intracellular vesicles) but did not alter the
quantity of VRUT in this fraction. Finally, AQP2-containing vesicles
immunoisolated from a low-density membrane fraction from renal inner medulla did
not contain immunoreactive VRUT. Thus vasopressin-mediated regulation of AQP2,
but not of VRUT, depends on regulated vesicular trafficking to the plasma
membrane.
PMID- 10198417
TI - Altered protein kinase C activation of Na+/Ca2+ exchange in mesangial cells from
salt-sensitive rats.
AB - The purpose of these studies was to determine whether there is a defect in
protein kinase C (PKC) regulation of the Na+/Ca2+ exchanger in cultured mesangial
cells (MC) from Dahl/Rapp salt-sensitive (S) and salt-resistant (R) rats. R and S
MCs were cultured, grown on coverslips, and loaded with fura 2 for measurement of
single cell cytosolic calcium concentration ([Ca2+]i) in a microscope-based
photometry system. Studies were performed in cells that were exposed to serum
(serum fed) and in cells that were serum deprived for 24 h. Baseline [Ca2+]i
values measured in a Ringer solution containing 150 mM NaCl were similar between
R and S MCs in both serum-fed and serum-deprived groups, although baseline
[Ca2+]i values were uniformly higher in the serum-deprived groups. Exchanger
activity was assessed by reducing extracellular Na (Nae) from 150 to 2 mM, which
resulted in movement of Na+ out of and Ca2+ into these cells (reverse-mode
Na+/Ca2+ exchange). PKC was activated in these cells with 15-min exposure to 100
nM phorbol 12-myristate 13-acetate (PMA). In the absence of PMA, the change in
[Ca2+]i (Delta[Ca2+]i) with reduction in Nae was similar between R and S MCs in
both serum-fed and serum-deprived groups, although the magnitude of Delta[Ca2+]i
was enhanced by serum deprivation. In both serum-fed and serum-deprived groups,
PMA significantly increased Delta[Ca2+]i in R but not S MCs. Upregulation of
exchanger activity in R MCs could be abolished by prior 24-h exposure to PMA, a
maneuver that downregulates PKC activity. Other studies were performed to
evaluate exchanger protein expression using monoclonal and polyclonal antibodies.
Immunoblots of PMA-treated cells revealed an increase in the levels of 70- and
120-kDa proteins in the crude membrane fraction of R but not S MCs, an increase
which was abrogated by prior 24-h PMA pretreatment and corresponded to reduction
in the 70-kDa protein in the crude cytosolic fraction. These data demonstrate
that PKC enhances Na+/Ca2+ exchange activity in MCs from R but not from S rats,
suggesting that there may be a defect in the PKC-Na+/Ca2+ exchange regulation
pathway in MCs of S rats.
PMID- 10198416
TI - Renal arteriolar Na+/Ca2+ exchange in salt-sensitive hypertension.
AB - The present studies were performed to assess Na+/Ca2+ exchange activity in
afferent and efferent arterioles from Dahl/Rapp salt-resistant (R) and salt
sensitive (S) rats. Renal arterioles were obtained by microdissection from S and
R rats on either a low-salt (0.3% NaCl) or high-salt (8.0% NaCl) diet. On the
high-salt diet, S rats become markedly hypertensive. Cytosolic calcium
concentration ([Ca2+]i) was measured in fura 2-loaded arterioles bathed in a
Ringer solution in which extracellular Na (Nae) was varied from 150 to 2 mM (Na
was replaced with N-methyl-D-glucamine). Baseline [Ca2+]i was similar in afferent
arterioles of R and S rats fed low- and high-salt diet. The change in [Ca2+]i
(Delta[Ca2+]i) during reduction in Nae from 150 to 2 mM was 80 +/- 10 and 61 +/-
3 nM (not significant) in afferent arterioles from R rats fed the low- and high
salt diet, respectively. In afferent arterioles from S rats on a high-salt diet,
Delta[Ca2+]i during reductions in Nae from 150 to 2 mM was attenuated (39 +/- 4
nM) relative to the Delta[Ca2+]i of 79 +/- 13 nM (P < 0.05) obtained in afferent
arterioles from S rats on a low-salt diet. In efferent arterioles, baseline
[Ca2+]i was similar in R and S rats fed low- and high-salt diets, and
Delta[Ca2+]i in response to reduction in Nae was also not different in efferent
arterioles from R and S rats fed low- or high-salt diets. Differences in
regulation of the exchanger in afferent arterioles of S and R rats were assessed
by determining the effects of protein kinase C (PKC) activation by phorbol 12
myristate 13-acetate (PMA, 100 nM) on Delta[Ca2+]i in response to reductions in
Nae from 150 to 2 mM. PMA increased Delta[Ca2+]i in afferent arterioles from R
rats but not from S rats. These results suggest that Na+/Ca2+ exchange activity
is suppressed in afferent arterioles of S rats that are on a high-salt diet. In
addition, there appears to be a defect in the PKC-Na+/Ca2+ exchange pathway that
might contribute to altered [Ca2+]i regulation in this important renal vascular
segment in salt-sensitive hypertension.
PMID- 10198418
TI - Expression of c-ret promotes morphogenesis and cell survival in mIMCD-3 cells.
AB - c-Ret, a protein tyrosine kinase receptor, and its ligand glial-derived
neurotropic factor (GDNF) are critical for early regulation of ureteric bud
development and nephrogenesis. To address whether c-ret directly initiates
epithelial cell morphogenesis, the c-ret receptor was expressed in murine inner
medullary collecting duct cells (mIMCD-3, a cell line of ureteric bud origin,
which has no detectable endogenous c-ret expression). Stable expression of wild
type c-ret was found to yield a constitutively tyrosine-phosphorylated receptor,
with no change after the addition of GDNF. Examination of mRNA from these cells
demonstrated the message for endogenous GDNF, suggesting that c-ret was
potentially being constitutively activated by an autocrine mechanism. When mIMCD
3 cells stably expressing the phosphorylated c-ret receptor were cultured in a
type I collagen matrix, they exhibited little GDNF-independent or -dependent
branching process formation at early time points compared with the known
morphogen hepatocyte growth factor (HGF) (48 h; control, 0.33 +/- 0.33; GDNF, 1.0
+/- 0.58, P = nonsignificant; and HGF, 6.33 +/- 0.33 processes/20 cell clusters,
P < 0.001), whereas extended culture (7 days) under serum-free conditions
revealed a marked increase in cell survival and the spontaneous development of
rudimentary branching process formation. Extended culture (7 days) of c-ret
expressing clones in type I collagen with the epithelial morphogens HGF and/or
epidermal growth factor (EGF) resulted in the development of complex three
dimensional spiny cysts, whereas parental mIMCD-3 cells died under these
conditions. We conclude that activated c-ret appears to mediate epithelial
morphogenesis by prolonging cell survival and, in conjunction with activation of
the morphogenic receptors c-met and the EGF receptor, initiates the events
required for very early branching morphogenesis.
PMID- 10198419
TI - Bradykinin inhibits ceramide production and activates phospholipase D in rabbit
cortical collecting duct cells.
AB - Recent reports suggest that inflammatory cytokines, growth factors, and
vasoconstrictor peptides induce sphingomyelinase (SMase) activity. This results
in the hydrolysis of sphingomyelin (SM) into ceramide, which is implicated in
various cellular functions. Although ceramide regulates phospholipase D (PLD)
activity, there is controversy about this relationship. Thus we investigated
whether the effect of bradykinin (BK), a proinflammatory factor and vasodilator,
was mediated by ceramide signal transduction and by PLD. In rabbit cortical
collecting duct (RCCD) cells, BK increased SM levels and decreased ceramide
levels in a time-dependent manner. Thus SMase activity was inhibited by BK. Also,
the production of ceramide was regulated in a concentration-dependent manner. The
BK-B1 antagonist [Lys-des-Arg9,Leu8]BK did not affect ceramide signal
transduction but the BK-B2 antagonist (Hoe-140) blocked the effect of BK on
SMase, suggesting that the BK-B2 receptor mediates BK-induced inhibition of
ceramide generation. Our results show that exogenous SMase significantly
hydrolyzed endogenous SM to form ceramide and weakly activated PLD. In contrast,
BK induced a significant activation of PLD. However, additive effects of BK and
ceramide on PLD activity were not observed. We concluded that in RCCD cells, the
BK-induced second messengers ceramide and phosphatidic acid were generated by
distinct signal transduction mechanisms, namely the SMase and PLD pathways.
PMID- 10198420
TI - CCAAT/enhancer binding protein-beta trans-activates murine nitric oxide synthase
2 gene in an MTAL cell line.
AB - Nitric oxide production by nitric oxide synthase 2 (NOS2) has been implicated in
epithelial cell injury from oxidative and immunologic stress. The NOS2 gene is
transcriptionally activated by lipopolysaccharide (LPS) and cytokines in
medullary thick ascending limb of Henle's loop (MTAL) cells and other cell types.
The 5'-flanking region of the NOS2 gene contains a consensus element for
CCAAT/enhancer binding proteins (C/EBP) at -150 to -142 that we hypothesized
contributes to NOS2 trans-activation in the mouse MTAL cell line ST-1. Gel shift
assays demonstrated LPS + interferon-gamma (IFN-gamma) induction of C/EBP family
protein-DNA complexes in nuclei harvested from the cells. Supershift assays
revealed that the complexes were comprised of C/EBPbeta, but not C/EBPalpha,
C/EBPdelta, or C/EBPepsilon. NOS2 promoter-luciferase genes harboring deletion or
mutation of the C/EBP box exhibited lower activities in response to LPS + IFN
gamma compared with wild-type NOS2 promoter constructs. Overexpression of a C/EBP
specific dominant-negative mutant limited LPS + IFN-gamma activation of the NOS2
promoter. In trans-activation assays, overexpression of C/EBPbeta stimulated
basal NOS2 promoter activity. Thus C/EBPbeta appears to be an important trans
activator of the NOS2 gene in the MTAL.
PMID- 10198421
TI - Apical proton secretion by the inner stripe of the outer medullary collecting
duct.
AB - The inner stripe of outer medullary collecting duct (OMCDis) is unique among
collecting duct segments because both intercalated cells and principal cells
secrete protons and reabsorb luminal bicarbonate. The current study characterized
the mechanisms of OMCDis proton secretion. We used in vitro microperfusion, and
we separately studied the principal cell and intercalated cell using differential
uptake of the fluorescent, pH-sensitive dye, 2', 7'-bis(2-carboxyethyl)-5(6)
carboxyfluorescein (BCECF). Both the principal cell and intercalated cell
secreted protons, as identified as Na+/H+ exchange-independent intracellular pH
(pHi) recovery from an intracellular acid load. Two proton transport activities
were identified in the principal cell; one was luminal potassium dependent and
Sch-28080 sensitive and the other was luminal potassium independent and luminal
bafilomycin A1 sensitive. Thus the OMCDis principal cell expresses both apical H+
K+-ATPase and H+-ATPase activity. Intercalated cell Na+/H+ exchange-independent
pHi recovery was approximately twice that of the principal cell and was mediated
by pharmacologically similar mechanisms. We conclude 1) the OMCDis principal cell
may contribute to both luminal potassium reabsorption and urinary acidification,
roles fundamentally different from those of the principal cell in the cortical
collecting duct; and 2) the OMCDis intercalated cell proton transporters are
functionally similar to those in the principal cell, raising the possibility that
an H+-K+-ATPase similar to the one present in the principal cell may contribute
to intercalated cell proton secretion.
PMID- 10198422
TI - Nitric oxide inhibits transcription of the Na+-K+-ATPase alpha1-subunit gene in
an MTAL cell line.
AB - Nitric oxide (NO) has been implicated as an autocrine modulator of active sodium
transport. To determine whether tonic exposure to NO influences active sodium
transport in epithelial cells, we established transfected medullary thick
ascending limb of Henle (MTAL) cell lines that overexpressed NO synthase-2 (NOS2)
and analyzed the effects of deficient or continuous NO production [with or
without NG-nitro-L-arginine methyl ester (L-NAME) in the culture medium,
respectively] on Na+-K+-ATPase function and expression. The NOS2-transfected
cells exhibited high-level NOS2 expression and NO generation, which did not
affect cell viability or cloning efficiency. NOS2-transfected cells were grown in
the presence of vehicle, NG-nitro-D-arginine methyl ester (D-NAME), or L-NAME for
16 h, after which 86Rb+ uptake assays, Northern analysis, or nuclear run-on
transcription assays were performed. The NOS2-transfected cells allowed to
produce NO continuously (vehicle or D-NAME) exhibited lower rates of ouabain
sensitive 86Rb+ uptake ( approximately 65%), lower levels of Na+-K+-ATPase alpha1
subunit mRNA ( approximately 60%), and reduced rates of de novo Na+-K+-ATPase
alpha1-subunit transcription compared with L-NAME-treated cells. These results
have uncovered a novel effect of NO to inhibit transcription of the Na+-K+-ATPase
alpha1-subunit gene.
PMID- 10198423
TI - Type II cAMP-dependent protein kinase regulates electrogenic ion transport in
rabbit collecting duct.
AB - cAMP mediates many of the effects of vasopressin, prostaglandin E2, and beta
adrenergic agents upon salt and water transport in the renal collecting duct. The
present studies examined the role of cAMP-dependent protein kinase (PKA) in
mediating these effects. PKA is a heterotetramer comprised of two regulatory (R)
subunits and two catalytic (C) subunits. The four PKA isoforms may be
distinguished by their R subunits that have been designated RIalpha, RIbeta,
RIIalpha, and RIIbeta. Three regulatory subunits, RIalpha, RIIalpha, and RIIbeta,
were detected by immunoblot and ribonuclease protection in both primary cultures
and fresh isolates of rabbit cortical collecting ducts (CCDs). Monolayers of
cultured CCDs grown on semipermeable supports were mounted in an Ussing chamber,
and combinations of cAMP analogs that selectively activate PKA type I vs. PKA
type II were tested for their effect on electrogenic ion transport. Short-circuit
current (Isc) was significantly increased by the PKA type II-selective analog
pairs N6-monobutyryl-cAMP plus 8-(4-chlorophenylthio)-cAMP or N6-monobutyryl-cAMP
plus 8-chloro-cAMP. In contrast the PKA type I-selective cAMP analog pair [N6
monobutyryl-cAMP plus 8-(6-aminohexyl)-amino-cAMP] had no effect on Isc. These
results suggest PKA type II is the major isozyme regulating electrogenic ion
transport in the rabbit collecting duct.
PMID- 10198424
TI - Endothelin mediates renal vascular memory of a transient rise in perfusion
pressure due to NOS inhibition.
AB - We investigated the renal responses to NO synthase (NOS) inhibition with N
monomethyl-L-arginine (L-NMA; 30 mg/kg) in anesthetized rats in which renal
perfusion pressure (RPP) to the left kidney was mechanically adjusted. Acute L
NMA increased blood pressure (BP, approximately 20%) and renal vascular
resistance (RVR) rose ( approximately 50%) in the right kidneys that were always
exposed to high RPP. In group 1, the left kidney was exposed to a transient
increase (5 min) in RPP which was then normalized, and the rise in RVR was
similar to the right kidney. In group 2 the left kidney was never exposed to high
RPP, and the rise in RVR was attenuated relative to the right kidney. In group 3,
rats were pretreated with the endothelin (ET) receptor antagonist Bosentan,
immediately before exposure of the left kidney to a transient increase in RPP,
and the rise in RVR was also attenuated relative to the right kidney. NOS
inhibition resulted in a natriuresis and diuresis in the right kidneys, and
approximately 50% of the natriuresis persisted in the left kidney of group 2, in
the absence of any rise in RPP. ET antagonism completely prevented the
natriuresis and diuresis in response to acute L-NMA in both left and right
kidneys. These data suggest that transient exposure to high RPP by NOS inhibition
prevents an appropriate vasodilatory response when RPP is lowered, due to the
intrarenal action of ET.
PMID- 10198425
TI - Transport characteristics of the apical anion exchanger of rabbit cortical
collecting duct beta-cells.
AB - To functionally characterize transport properties of the apical anion exchanger
of rabbit beta-intercalated cells, the mean change in anion exchange activity,
dpHi/dt (where pHi is intracellular pH), was measured in response to lumen Cl-
replacement with gluconate in perfused cortical collecting ducts (CCDs). beta
Cell apical anion exchange was not affected by 15-min exposure to 0.2 mM lumen
DIDS in the presence of 115 mM Cl-. In contrast, apical anion exchange was
significantly inhibited by 0.1 mM lumen DIDS in the absence of Cl-. beta-Cell
apical anion exchange was unchanged by 15 mM maleic anhydride, 10 mM
phenylglyoxal, 0.2 mM niflumic acid, 1 mM edecrin, 1 mM furosemide, 1 mM
probenecid, or 0.1 mM diphenylamine-2-carboxylate. However, beta-cell apical
anion exchange was inhibited by alpha-cyano-4-hydroxycinnamic acid, with an IC50
of 2.4 mM. Substitution of either sulfate or gluconate for lumen Cl- resulted in
a similar rate of alkalinization. Conversely, pHi was unchanged by substitution
of sulfate for lumen gluconate, confirming the lack of transport of sulfate on
the beta-cell apical anion exchanger. Taken together, the results demonstrate a
distinct "fingerprint" of the rabbit CCD beta-cell apical anion exchanger that is
unlike that of other known anion exchangers.
PMID- 10198426
TI - Stoichiometry and Na+ binding cooperativity of rat and flounder renal type II Na+
Pi cotransporters.
AB - The stoichiometry of the rat and flounder isoforms of the renal type II sodium
phosphate (Na+-Pi) cotransporter was determined directly by simultaneous
measurements of phosphate (Pi)-induced inward current and uptake of radiolabeled
Pi and Na+ in Xenopus laevis oocytes expressing the cotransporters. There was a
direct correlation between the Pi-induced inward charge and Pi uptake into the
oocytes; the slope indicated that one net inward charge was transported per Pi.
There was also a direct correlation between the Pi-induced inward charge and Na+
influx; the slope indicated that the influx of three Na+ ions resulted in one net
inward charge. This behavior was similar for both isoforms. We conclude that for
both Na+-Pi cotransporter isoforms the Na+:Pi stoichiometry is 3:1 and that
divalent Pi is the transported substrate. Steady-state activation of the currents
showed that the Hill coefficients for Pi were unity for both isoforms, whereas
for Na+, they were 1.8 (flounder) and 2.5 (rat). Therefore, despite significant
differences in the apparent Na+ binding cooperativity, the estimated Na+:Pi
stoichiometry was the same for both isoforms.
PMID- 10198427
TI - Npw38, a novel nuclear protein possessing a WW domain capable of activating basal
transcription.
AB - We have found a novel cDNA encoding a 265 amino acid protein possessing a WW
domain in our full-length cDNA bank. The WW domain was sandwiched between an
acidic region and an acidic-basic amino acid repetitive region. In vitro
transcription/translation of the cDNA produced a 38 kDa product that was also
found in the cell lysate by western blot analysis. Thus this protein is named the
nuclear protein containing a WW domain with a molecular mass of 38 kDa, Npw38.
Immunofluorescence studies and expression of a fusion protein to a green
fluorescent protein revealed that this protein is localized in the nucleus. Npw38
was shown to be capable of binding to a poly(rG) resin. Interestingly, the WW
domain of Npw38 was found to function as a transcriptional activator in CHO cells
using the GAL4 DNA-binding fusion system. Furthermore, the WW domains of human
YAP and Pin1 were demonstrated to have a similar transcription-promoting
activity. Combined mutation of the conserved first and second Trp residues and a
hydrophobic triplet of TyrTyrTrp in the WW domain of Npw38 abolished the
transcription-promoting activity, but single mutations of these sites did not.
These results suggest that some WW domains potentially possess transcription
promoting activity in mammalian cells.
PMID- 10198428
TI - The chicken HPRT gene: a counter selectable marker for the DT40 cell line.
AB - We describe the cloning, characterisation and chromosomal mapping of the chicken
hprt gene together with the construction of two counter selectable hprt-/- DT40
derived cell lines. One of these cell lines contains a stably integrated gene
encoding a conditionally active cre recombinase and thus allows efficient
manipulation of targeted loci by site-specific recombination. These cell lines
will enhance the utility of the hyper-recombinogenic DT40 cell line as a system
for the genetic analysis of cell autonomous functions in vertebrates and as a
tool for mammalian chromosome engineering.
PMID- 10198429
TI - Versatile derivatisation of solid support media for covalent bonding on DNA
microchips.
AB - A chemistry was developed that permits on DNA-arrays both the covalent
immobilisation of pre-fabricated nucleic acids-such as oligonucleotides, PCR
products or peptide nucleic acid oligomers-and the in situ synthesis of such
compounds on either glass or polypropylene surfaces. Bonding was found to be
stable even after some 30 cycles of stripping. Due to a dendrimeric structure of
the linker molecule, the loading can be modified in a controlled manner and
increased beyond the capacity of glass without negative effects on hybridisation
efficiency. Also, the chemistry warrants the modulation of other surface
properties such as charge or hydrophobicity. Preferentially, attachment of
nucleic acids takes place only via the terminal amino-group of amino-modified
oligonucleotides or the terminal hydroxyl-group of unmodified molecules so that
the entire molecule is accessible to probe hybridisation. This derivatisation
represents a support chemistry versatile enough to serve nearly all current forms
of DNA-arrays or microchips.
PMID- 10198431
TI - Spectral and physical characterization of the inverted terminal repeat DNA
structure from adenoassociated virus 2.
AB - An oligodeoxynucleotide (ODN) that includes elements found in secondary
structures at the 5'- and 3'- ends of adenoassociated virus 2 virion DNA was
synthesized by ligation of three overlapping ODNs. The most stable secondary
structure was calculated to be branched, with a 61 bp duplex stem, terminating in
a three-way junction with 9 bp arms. The electrophoretic mobility of the ODN is
slower than expected for normal duplex DNA of the same size, suggesting a bent or
branched conformation. CD spectra indicate that the ITR structure is largely B
form DNA, although there is a slight blue shift compared to the spectra of the
isolated stem and loop elements. Thermal melting experiments indicate that the
hairpin is significantly more stable than the isolated stem and loop elements.
Singular value decomposition of UV spectra obtained as a function of temperature
indicates that four species contribute to changes in the spectra upon
denaturation, indicating that the melting is not a simple two-state process.
Characterization of the branched ODN by differential scanning calorimetry permits
estimation of the enthalpy of melting by a model-free analysis, yielding
DeltaHcal= 614 kcal mol-1. This value agrees with the enthalpy computed for the
most stable secondary structure.
PMID- 10198430
TI - The Saccharomyces cerevisiae Sgs1 helicase efficiently unwinds G-G paired DNAs.
AB - The Saccharomyces cerevisiae Sgs1p helicase localizes to the nucleolus and is
required to maintain the integrity of the rDNA repeats. Sgs1p is a member of the
RecQ DNA helicase family, which also includes Schizo-saccharomyces pombe Rqh1,
and the human BLM and WRN genes. These genes encode proteins which are essential
to maintenance of genomic integrity and which share a highly conserved helicase
domain. Here we show that recombinant Sgs1p helicase efficiently unwinds guanine
guanine (G-G) paired DNA. Unwinding of G-G paired DNA is ATP- and Mg2+-dependent
and requires a short 3' single-stranded tail. Strikingly, Sgs1p unwinds G-G
paired substrates more efficiently than duplex DNAs, as measured either in direct
assays or by competition experiments. Sgs1p efficiently unwinds G-G paired
telomeric sequences, suggesting that one function of Sgs1p may be to prevent
telomere-telomere interactions which can lead to chromosome non-disjunction. The
rDNA is G-rich and has considerable potential for G-G pairing. Diminished ability
to unwind G-G paired regions may also explain the deleterious effect of mutation
of Sgs1 on rDNA stability, and the accelerated aging characteristic of yeast
strains that lack Sgs1 as well as humans deficient in the related WRN helicase.
PMID- 10198432
TI - Theoretical calculations, synthesis and base pairing properties of
oligonucleotides containing 8-amino-2'-deoxyadenosine.
AB - Theoretical calculations on double and triple helices containing 8-amino-2'
deoxyadenosine were made to analyze the possible differences in base pairing
properties between 8-aminoadenine and adenine. These calculations indicate a
strong preferential stabilization of the triplex over the duplex when adenine is
replaced by 8-aminoadenine. In addition, a protected phosphoramidite derivative
of 8-amino-2'-deoxyadenosine was prepared for the introduction of 8-aminoadenine
into synthetic oligonucleotides using the phosphite-triester approach. DNA triple
helical structures are normally observed at acidic pH. However, when
oligonucleotides carrying 8-aminoadenine are used, very stable triple helical
structures can be observed even at neutral pH. Biological applications of triple
helices could benefit from the use of 8-aminoadenine derivatives.
PMID- 10198433
TI - Role of DNAS1L3 in Ca2+- and Mg2+-dependent cleavage of DNA into oligonucleosomal
and high molecular mass fragments.
AB - Ca2+- and Mg2+-dependent endonucleases have been implicated in DNA fragmentation
during apoptosis. We have demonstrated that particular nucleases of this type are
inhibited by poly(ADP-ribosyl)ation and suggested that subsequent cleavage of
PARP by caspase-3 might release these nucleases from poly(ADP-ribosyl)ation
induced inhibition. Hence, we purified and partially sequenced such a nuclease
isolated from bovine seminal plasma and identified human, rat and mouse homologs
of this enzyme. The extent of sequence homology among these nucleases indicates
that these four proteins are orthologous members of the family of DNase I-related
enzymes. We demonstrate that the activation of the human homolog previously
specified as DNAS1L3 can induce Ca2+- and Mg2+-dependent DNA fragmentation in
vitro and in vivo. RT-PCR analysis failed to detect DNAS1L3 mRNA in HeLa cells
and nuclei isolated from these cells did not exhibit internucleosomal DNA
fragmentation when incubated in the presence of Ca2+and Mg2+. However, nuclei
isolated from HeLa cells that had been stably transfected with DNAS1L3 cDNA
underwent such DNA fragmentation in the presence of both ions. The Ca2+ionophore
ionomycin also induced internucleosomal DNA degradation in transfected but not in
control HeLa cells. Transverse alternating field electrophoresis revealed that in
nuclei from transfected HeLa cells, but not in those from control cells, DNA was
cleaved into fragments of >1000 kb in the presence of Mg2+; addition of Ca2+in
the presence of Mg2+resulted in processing of the >1000 kb fragments into 50 kb
and oligonucleosomal fragments. These results demonstrate that DNAS1L3 is
necessary for Ca2+- and Mg2+-dependent cleavage of DNA into both oligonucleosomal
and high molecular mass fragments in specific cell types.
PMID- 10198434
TI - Combinatorial selection of high affinity RNA ligands to live African
trypanosomes.
AB - African trypanosomiasis is a parasitic disease caused by a specific class of
protozoan organisms. The best-studied representative of that group is Trypanosoma
brucei which is transmitted by tsetse flies and multiplies in the blood of many
mammals. Trypanosomes evade the immune system by altering their surface structure
which is dominated by a layer of a variant surface glycoprotein (VSG). Although
invariant surface proteins exist, they are inaccessible to the humoral immune
response. Using a combinatorial selection method in conjunction with live
trypanosomes as the binding target, we show that short RNA ligands (aptamers) for
constant surface components can be isolated. We describe the selection of three
classes of RNA aptamers that crosslink to a single 42 kDa protein located within
the flagellar pocket of the parasite. The RNAs associate rapidly and with high
affinity. They do not discriminate between two different trypanosome VSG variant
strains and, furthermore, are able to bind to other trypanosome strains not used
in the selection protocol. Thus, the aptamers have the potential to function as
markers on the surface of the extracellular parasite and as such they might be
modified to function as novel drugs against African trypanosomiasis.
PMID- 10198435
TI - Transcription analysis of the telomeric repeat-specific retrotransposons TRAS1
and SART1 of the silkworm Bombyx mori.
AB - The telomeres of the silkworm Bombyx mori consist of (TTAGG)n repeats and harbor
a large number of sequence-specific non-LTR retrotransposons such as TRAS1 and
SART1. In order to ascertain if TRAS1 and SART1 are transcribed in vivo and if
there is a novel transcription mechanism peculiar to the sequence-specific
retrotransposons, we studied their transcription. We detected transcripts of
TRAS1 and SART1 by northern hybridization in many tissues and the BmN4 cell line
of the silkworm. 5'-Rapid amplification of cDNA ends analysis showed that
transcription of both elements was initiated precisely from their own 5'-ends and
that most of their genomic copies contained these initiation sites. TRAS1
contained an internal promoter and positively regulating elements in the +1/+581
nucleotides in its 2432 bp 5'-untranslated region (UTR). We could not, however,
detect any promoter activity in the SART1 5'-UTR. This difference may be related
to the fact that only TRAS1 contained an initiator-like element at its 5'-end.
Placing 1-52 units of the telomeric repeat (TTAGG)n upstream of TRAS1 reduced
transcription 5-fold. The evidence suggests that most of the TRAS1 genomic copies
within the telomeric repeats are weakly transcribed in vivo.
PMID- 10198436
TI - A role for the yeast SWI/SNF complex in DNA replication.
AB - The yeast SWI/SNF complex is required for expression of many genes and for the
full functioning of several transcriptional activators. Genetic and biochemical
studies indicate that SWI/SNF uses the energy of ATP hydrolysis to antagonize
chromatin-mediated transcriptional repression. We have tested the possibility
that SWI/SNF might also play a role in DNA replication. A mitotic minichromosome
stability assay was used to investigate the replication efficiency of a variety
of autonomous replication sequences (ARSs) in the presence and absence of
SWI/SNF. The stability of minichromosomes that contain ARS1, ARS309 or ARS307 is
not altered by lack of SWI/SNF, whereas the functioning of ARS121 is crippled
when SWI/SNF is inactivated. The SWI/SNF dependence of ARS121 does not require
the replication enhancer factor, ABF1, and thus, it appears to be a property of a
minimal ARS121 origin. Likewise, a minimal derivative of ARS1 that lacks the ABF1
replication enhancer acquires SWI/SNF dependence. Replacing the ABF1 binding site
at ARS1 with a binding site for the LexA-GAL4 chimeric activator also creates a
SWI/SNF-dependent ARS. Our studies suggest that the SWI/SNF chromatin remodeling
complex can play a role in both replication and transcription and, furthermore,
that SWI/SNF dependence of ARS elements is a property of both an ARS-specific
replication enhancer and the overall organization of ARS sequence elements.
PMID- 10198437
TI - Conservation of structure and cold-regulation of RNA-binding proteins in
cyanobacteria: probable convergent evolution with eukaryotic glycine-rich RNA
binding proteins.
AB - The rbp gene family of the cyanobacterium Anabaena variabilis strain M3 consists
of eight members that encode small RNA-binding proteins containing a single RNA
recognition motif (RRM). Similar genes are found in the genomes of Synechocystis
sp. PCC6803, Helicobacter pylori and Treponema pallidum, but are absent from the
other completely sequenced prokaryotic genomes. The expression of the rbp genes
of Anabaena is induced by low temperature, with the exception of the rbpD gene.
We found four stretches of conserved sequences in the 5'-untranslated region of
the cyanobacterial rbp genes that are known to be induced by low temperature. The
cold-regulated Rbp proteins contain a short C-terminal glycine-rich domain. In
this respect, these proteins are similar to plant and mammalian glycine-rich RNA
binding proteins (GRPs), which also contain a single RRM domain with a C-terminal
glycine-rich domain and are highly expressed at low temperature. Detailed
phylogenetic analysis showed, however, that the cyanobacterial Rbp proteins and
the eukaryotic GRPs do not belong to a single lineage, but that the glycine-rich
domains are likely to have been added independently. The cold-regulation of both
types of proteins is also likely to have evolved independently. Furthermore, the
chloroplast RNA-binding proteins are not likely to have originated from the Rbp
proteins of endosymbiont cyanobacterium, but are supposed to have diverged from
the GRPs. These results suggest that the cyanobacterial Rbp proteins and the
eukaryotic GRPs are similar in both structure and regulation, but that this
apparent similarity has resulted from convergent evolution.
PMID- 10198439
TI - The yeast inositol-sensitive upstream activating sequence, UASINO, responds to
nitrogen availability.
AB - The INO1 gene of yeast is expressed in logarithmically growing, wild-type cells
when inositol is absent from the medium. However, the INO1 gene is repressed when
inositol is present during logarithmic growth and it is also repressed as cells
enter stationary phase whether inositol is present or not. In this report, we
demonstrate that transient nitrogen limitation also causes INO1 repression. The
repression of INO1 in response to nitrogen limitation shares many features in
common with repression in response to the presence of inositol. Specifically, the
response to nitrogen limitation is dependent upon the presence of a functional
OPI1 gene product, it requires ongoing phosphatidylcholine biosynthesis and it is
mediated by the repeated element, UASINO, found in the promoter of INO1 and other
co-regulated genes of phospholipid biosynthesis. Thus, we propose that repression
of INO1 in response to inositol and in response to nitrogen limitation occurs via
a common mechanism that is sensitive to the status of ongoing phospholipid
metabolism.
PMID- 10198438
TI - Differential import of nuclear-encoded tRNAGly isoacceptors into solanum
Tuberosum mitochondria.
AB - In potato ( Solanum tuberosum ) mitochondria, about two-thirds of the tRNAs are
encoded by the mitochondrial genome and one-third is imported from the cytosol.
In the case of tRNAGly isoacceptors, a mitochondrial-encoded tRNAGly(GCC) was
found in potato mitochondria, but this is likely to be insufficient to decode the
four GGN glycine codons. In this work, we identified a cytosolic tRNAGly(UCC),
which was found to be present in S.tuberosum mitochondria. The cytosolic
tRNAGly(CCC) was also present in mitochondria, but to a lesser extent. By
contrast, the cytosolic tRNAGly(GCC) could not be detected in mitochondria. This
selective import of tRNAGly isoacceptors into S. tuberosum mitochondria raises
further questions about the mechanism under-lying the specificity of the import
process.
PMID- 10198440
TI - Open complex formation during transcription initiation at the Escherichia coli
galP1 promoter: the role of the RNA polymerase alpha subunit at promoters lacking
an UP-element.
AB - We have studied the role of the C-terminal domain of the alpha subunit (alphaCTD)
of Escherichia coli RNA polymerase during transcription initiation at promoters
lacking an UP-element. The temperature requirement for open complex formation was
used as an indication of the kinetics of this process. We have previously shown
that alphaCTD is required for transcription initiation at low temperature at the
galP1 promoter, a promoter containing an UP-element. DNase I footprinting has
been used to reveal the structure of open promoter complexes and the temperature
requirement for open complex formation has been determined using potassium
permanganate as a probe. In this work we show that, although alphaCTD is not
absolutely required for transcription initiation at promoters lacking an UP
element, it does play a role during transcription initiation. This role is
independent of the sequence of the promoter upstream from the -35 region and does
not require stable alphaCTD-DNA interactions as determined by DNase I
footprinting. The role of alphaCTD at promoters lacking an UP-element is
discussed.
PMID- 10198441
TI - A non-isotopic assay for histone deacetylase activity.
AB - Inhibitors of histone deacetylase (HD) bear great potential as new drugs due to
their ability to modulate transcription and to induce apoptosis or
differentiation in cancer cells. To study the activity of HD and the effect of
potential inhibitors in vitro so far only radio-active assays have existed. For
the search of new inhibitors and for the use in HD identification and
purification we established a simple, non-radioactive assay that allows screening
of large numbers of compounds. The assay is based on an aminocoumarin derivative
of an Omega-acetylated lysine as enzyme substrate.
PMID- 10198442
TI - Efficient bicistronic expression of cre in mammalian cells.
AB - Cre recombinase-mediated DNA recombination is proving to be a powerful technique
for the generation of mosaic mutant mice. To develop this technology further, we
have altered the cre gene to enhance its expression in mammalian cells and have
tested its efficiency of expression in a bicistronic message. Using a transient
transfection assay, we found that the extension of a eukaryotic translation
initiation consensus sequence, the insertion of two N-terminal amino acids, and
the mutation of a cryptic splice acceptor site did not detectably alter Cre
recombinase activity. The addition of either of two introns resulted in an
approximately 2-fold increase in recombination frequency. We then tested the
relative efficacy of Cre-mediated recombination in several bicistronic messages
having the encephalomyocarditis virus internal ribosome entry site (IRES).
Recombination frequencies were only reduced 2-fold relative to a comparable
monocistronic cre gene. The latter results indicate that it will be possible to
generate transgenic mouse strains having tissue-specific expression of the Cre
recombinase through integration of an IRES-cre gene without disabling the
targeted gene.
PMID- 10198443
TI - Pacemakers promising for repeated fainting spells.
PMID- 10198444
TI - Stopping blood-pressure medications safely.
PMID- 10198445
TI - Chest-pain units: a new place for coronary care.
PMID- 10198446
TI - Pravastatin shown to reduce stroke risk after heart attacks.
PMID- 10198447
TI - Ask the doctor. You have published some information in recent issues that high
levels of C-reactive protein predict an increased chance of cardiovascular
problems. Can anything bring C-reactive protein levels down? Would aspirin help?
And if so, how much?
PMID- 10198448
TI - Heart disease. The search for new culprits.
PMID- 10198449
TI - Schizophrenia and the brain - part I.
PMID- 10198450
TI - Mental health care above and below the 49th parallel.
PMID- 10198451
TI - Cheating.
PMID- 10198452
TI - Insomnia. Part II: remedies.
PMID- 10198453
TI - Residential radon: is it a problem in your backyard?
PMID- 10198454
TI - I am a 54-year-old man. My father is a healthy 84-year-old, but my two brothers
(59 and 61 years old) have been diagnosed with prostate cancer within the past
year. I am worried not only about myself but about my two sons. Is there any hope
of a vaccine for prostate cancer?
PMID- 10198455
TI - Sexual dysfunction.
PMID- 10198456
TI - News that isn't ready to use.
PMID- 10198457
TI - Chronic conditions. Low thyroid.
PMID- 10198459
TI - Quality of care. Making the most of your medical visit.
PMID- 10198458
TI - Diagnosis and treatment. Osteoporosis update.
PMID- 10198460
TI - Mom and mitochondria.
PMID- 10198461
TI - Ask the doctor. In your article on Alzheimer's disease (March, 1999), you mention
"high doses of vitamin E" as helpful in slowing the progression of the condition.
Specifically, what dose is recommended?
PMID- 10198462
TI - Ask the doctor. A year ago, my doctor recommended that I have a pacemaker because
my pulse rate was too slow (38 on a monitor, 48 taken by hand). I did, and the
rate of the pacemaker was set at 60. I am 90 years old, and my entire life my
heart rate has been fortyish. Is my future affected by my pacemaker's timing?
PMID- 10198463
TI - Ask the doctor. I read in your newsletter and elsewhere that beta blockers can
help people with heart failure, but my doctor has been reluctant to try them on
me. Why is he so nervous?
PMID- 10198464
TI - Dietary diversity and body fat.
PMID- 10198465
TI - Ask the doctor. I've been taking tamoxifen for several months after completing
treatment for breast cancer. My doctor prescribed it primarily to lower my risk
of developing cancer in my unaffected breast. As a result of chemotherapy, I
underwent menopause abruptly. Tamoxifen has worsened my symptoms, especially hot
flashes and vaginal dryness. Other than stopping the tamoxifen, are there ways to
deal with the side effects?
PMID- 10198466
TI - Motif-dependent DNA analysis of a methicillin-resistant Staphylococcus aureus
collection.
AB - Methicillin-resistant Staphylococcus aureus (MRSA) has become a major nosocomial
pathogen in recent years. Once introduced into the hospital environment, MRSA can
spread rapidly, and its subsequent treatment is often difficult as it may be
simultaneously resistant to several antibiotics. A useful strategy both to
identify the source of infection and to monitor specific infecting strains would
be beneficial, facilitating the implementation of control and preventive
measures. In this study, a typing strategy, based on the amplification of a
conserved repeat-motif in the bacterial genome, was applied in a hospital setting
to analyse an MRSA collection. Using a fluorescent-labelled oligonucleotide
primer RW3A, which annealed to several dispersed short-repeat sequences occurring
throughout the bacterial genome, DNA amplification fingerprint patterns were
produced by polymerase chain reaction (PCR). Thirty-nine MRSA isolates were
successfully analysed using conventional agarose gel electrophoresis and GeneScan
technology. The latter method provides a finer resolution, making use of
capillary electrophoresis in an ABI Prism 310 genetic analyser. The fluorescent
detection approach can facilitate the construction of a fingerprint database
which can be accessed for comparison of any isolate. Quantitative analysis of all
patterns divided the MRSA isolates into four different groups, based on their
RW3A fingerprints. Most of the isolates (88%) were assigned to one of three main
groups, while the remaining isolates (12%) comprised a fourth, miscellaneous
group.
PMID- 10198467
TI - Endomysial antibody detection using human umbilical cord tissue as substrate:
reactivity of cells in Wharton's jelly.
AB - The measurement of immunoglobulin A (IgA) endomysial antibodies is now
established as an important diagnostic test in gluten-sensitive disease. Monkey
oesophagus is the commonly used tissue substrate, but it has been proposed that
human umbilical cord tissue may be a suitable alternative for antibody detection.
In this study, we report a modified method of examining endomysial antibody
reactivity with cord tissue. This involves examination of antibody reactivity
with cells in Wharton's jelly, and with umbilical cord blood vessel. A total of
370 patients being investigated for coeliac disease were studied and this
diagnosis was established in 42. Endomysial antibodies were found in all 42 using
umbilical cord tissue, and the test results were confirmed with monkey oesophagus
substrate. In three of the remaining 328 non-coeliacs, a false-positive
endomysial antibody test was noted and small intestine histology was normal in
these patients. All positive sera were found to react with cells in Wharton's
jelly, and reticular staining of blood vessels was also present. Examination for
immunofluorescence in both Wharton's jelly and blood vessel components of cord
tissue greatly simplified test interpretation.
PMID- 10198468
TI - Extended-spectrum beta-lactamase-producing Klebsiella pneumoniae in a Dublin
paediatric hospital.
AB - Klebsiella pneumoniae resistant to third-generation cephalosporins and gentamicin
was isolated from two patients in a paediatric intensive care unit within a two
week period. The double-disc diffusion test indicated the presence of an extended
spectrum beta-lactamase (ESBL). The unit was closed to admissions, and stringent
infection control procedures were implemented. Environmental screening and
screening of staff and patients on the unit were commenced. Two weeks later, K.
pneumoniae with an identical antibiogram was isolated from the urine of a patient
in a different ward. Blood-culture isolates possessed the K16 antigen, while the
urine isolate was non-typeable. The isolates were shown to be similar when
banding patterns of XbaI chromosomal DNA digests were compared. The resistance to
the extended-spectrum cephalosporins was shown to be transferable in association
with a large plasmid > 98 mDa. Resistance to gentamicin always co-transferred
with beta-lactamase resistance and appeared to be encoded by the same plasmid.
PMID- 10198469
TI - Metronidazole sensitivity testing of Helicobacter pylori: the importance of
media.
AB - Successful triple-therapy treatment for Helicobacter pylori infection depends
upon metronidazole (Mz) susceptibility, and many hospital laboratories routinely
screen H. pylori isolates for Mz resistance using disc diffusion methods. We
report the importance of culture medium when testing for metronidazole
susceptibility. In this laboratory, Mz resistance in strains of H. pylori from
patients in our area was found in approximately 80%. In other areas, Mz
resistance is found in approximately 30%. This high rate of Mz resistance was not
reflected clinically. Added haemin (X factor) and menadione in the culture medium
drastically reduced zone size to Mz and also interfered with the minimal
inhibitory concentration (MIC) as determined by Etest. When strains of H. pylori
were re-tested on media which did not contain X factor or menadione, Mz
resistance fell from 80% to 39%, a level similar to that seen in other areas.
PMID- 10198470
TI - Quantitation of carboxyhaemoglobin in blood: external quality assessment of
techniques.
AB - The performance of four dedicated carbon monoxide (CO)-oximeters (AVL, Chiron,
IL, Radiometer), spectrophotometry with and without dithionite, spectrophotometry
by second derivative, and the Whitehead and Worthington precipitation technique
for the measurement of carboxyhaemoglobin in blood was compared by a mean of 136
participants in the United Kingdom National External Quality Assessment Scheme in
21 samples formulated to contain from 4% to 48% carboxyhaemoglobin. The dedicated
instruments and spectrophotometry by second derivative were of significantly
higher precision than the other techniques, producing fewer measurements rejected
as being > 3 standard deviations from the sample mean and having a lower standard
deviation for non-rejected measurements. The AVL instrument and spectrophotometry
by second derivative had a significant positive bias compared to the other
techniques. The Whitehead and Worthington method was of an unacceptably low
precision.
PMID- 10198471
TI - Verocytotoxin-producing Escherichia coli O157: public health and microbiological
significance.
AB - Escherichia coli O157 was recognised as a human pathogen in the late 1970s, its
public health significance being recognised in 1982 when it was implicated in a
large outbreak of infection associated with a fast-food restaurant in North
America. Incidence of infection in the population is relatively low compared to
other enteric pathogens; however, this organism causes a spectrum of disease
increasing in severity from a mild diarrhoeal illness to haemorrhagic colitis,
haemolytic uraemic syndrome (HUS) and, in some cases, death. Production of
verocytotoxin and intimin, and the presence of a 60 mDa plasmid are thought to be
important virulence factors; however, many currently unidentified factors may
also contribute. The infectious dose of this organism is low and reports of food
borne, water-borne and person-to-person transmission have occurred, including
several laboratory-acquired infections. Techniques for isolation, identification
and confirmation of these organisms, based on cultural, immunological and
molecular detection, are described. Additionally, schemes have been developed to
type these organisms for epidemiological investigation, and the roles of phage
typing and genotyping are discussed. These enable identification of sources and
the introduction of intervention strategies for prevention of spread in the
community.
PMID- 10198472
TI - Ageing of the heart.
AB - Ageing of the heart is associated with a number of characteristic morphological,
histological and biochemical changes. However, not all observed changes with age
are associated with a deterioration in function. The high prevalence of
hypertension and ischaemic heart disease makes distinction between normal ageing
changes and the effects of underlying cardiovascular disease processes difficult.
In this review, an attempt has been made to separate age-related changes from
those related to disease, and to outline their significance for cardiac
performance. Disease-independent changes in the ageing heart which are associated
with a reduction in function include a reduction in the number of myocytes and
cells within the specialised conduction tissue, the development of cardiac
fibrosis, a reduction in calcium transport across membranes, lower capillary
density and decreases in the intracellular response to beta-adrenergic
stimulation. Other characteristic changes, such as epicardial fat deposition and
'brown atrophy' due to intracellular lipofuscin deposits, appear to be merely
symptomatic of the ageing process without any obvious effects on function. Some
of the age-associated changes in the heart can be reversed, at least partially,
by exercise or specific drugs. It remains, however, unclear whether this would
result in any definite advantages for the individual. The mechanisms guiding
proliferation or non-proliferation of myocytes and the development of fibrosis
are current topics for research and may lead to new preventive approaches to
ageing processes in the heart.
PMID- 10198473
TI - The emergence of enterococci as a cause of nosocomial infection.
AB - Enterococci have traditionally been regarded as low-grade pathogens but have
emerged as an increasingly important cause of nosocomial infection. The rise in
hospital-acquired enterococcal infection has been in part due to the increased
use of broad-spectrum antibiotics and the rising number of severely ill patients.
The intrinsic resistance of enterococci to many antimicrobial agents, and the
acquisition of resistance to the few antibiotics available for treatment, has led
to real therapeutic difficulties. The microbiological laboratory has an important
role to play in the control of enterococcal infection through surveillance, and
should be able to identify antibiotic-resistant strains likely to cause a
problem. Infection control measures, such as source isolation of infected or
colonised patients, should be considered. The possibility that vancomycin
resistant strains of enterococci are entering the community via the food chain
indicates the need for greater control of the use of glycopeptide antibiotics in
animal feed.
PMID- 10198474
TI - Cyclospora species as a cause of diarrhoea in humans.
AB - Within the past 10 years, the coccidian parasite Cyclospora cayetanensis has been
clearly recognised as a cause of protracted diarrhoea in humans. Heavy infection
results in inflammation and epithelial injury in the duodenum and jejunum. Of the
multiple symptoms, diarrhoea may neither be the presenting nor predominant one.
Following an incubation period of 12 hours to 11 days, the abrupt onset of watery
diarrhoea occurring in a relapsing cyclic pattern is characteristic, lasting from
six to eight weeks in immunocompetent patients, but three months in the
immunocompromised. Of worldwide distribution, it is endemic in certain regions
where it can be associated with rainy seasons. Outbreaks or isolated cases may
also occur in developed countries. Contaminated water can transmit the oocysts,
and usual control procedures for potable water supplies fail to detect the
parasite, which resists chlorination. Diagnosis depends upon laboratory
investigations, usually faecal microscopy. For reliable detection of
characteristic oocysts in the faeces, special procedures may be necessary.
Trimethoprim-sulphamethoxazole is established as the treatment of choice and
leads to rapid relief of symptoms, although relapse in immunocompromised patients
may require secondary prophylaxis.
PMID- 10198475
TI - Sectioning human bone.
PMID- 10198476
TI - Female urinary incontinence: another common chronic illness.
PMID- 10198477
TI - Death notification and bereavement in general practice: optimizing the quality of
care.
PMID- 10198478
TI - Female urinary incontinence: long-term follow-up after treatment in general
practice.
AB - BACKGROUND: Several reports have been published showing that women with urinary
incontinence (UI) can be taken care of and treated satisfactorily in general
practice. AIM: To find out whether the treatment of women with UI in general
practice is effective also in the long term. METHOD: One hundred and five women
with UI who consulted their general practitioner (GP) were examined and treated
according to a treatment protocol. Treatment options were pelvic floor exercises,
electrical stimulation, oestrogen supplements, bladder training, and protective
pads. Three to six years after inclusion, all women received a postal
questionnaire to evaluate the long-term effectiveness of treatment. Women who had
been referred to a specialist were excluded. RESULTS: Eighty out of 82 eligible
patients answered the questionnaire after a mean follow-up period of 56 months.
Twenty-seven per cent were continent, 26% much better, 23% a little better, 21%
unchanged, and 3% were worse compared with before the treatment. The median score
on a 100 mm visual analogue scale was 16 compared with 31 before treatment, and
the percentage of women that were 'much' or 'a great deal' bothered by UI was
reduced from 35% to 12%. The percentage of women with severe UI was reduced from
59% to 30%, and the number of women using pads was reduced from 62% to 39%.
CONCLUSION: This study confirms that management of female UI in general practice
is effective also in the long term.
PMID- 10198479
TI - Long-term effect of treatment of female incontinence in general practice.
AB - BACKGROUND: Urinary incontinence in women can be treated successfully by the
general practitioner. However, little is known about the long-term effects of
conservative treatment. AIM: To evaluate the long-term effect of treatment of
female incontinence by the general practitioner (pelvic floor exercises, and
bladder training) in female urinary incontinence. METHOD: A total of 88 women,
aged between 20 and 65, who had participated in a controlled trial between 1987
and 1990, were contacted to participate in a five-year follow-up study. Stress
incontinence and urge incontinence were treated by means of pelvic floor
exercises and bladder training respectively, while a mixed incontinence was
treated by bladder training followed by pelvic floor exercises. The outcome
measures were a constructed scale for the severity of the incontinence, a seven
day bladder chart, and a questionnaire concerning patients' opinions. All
patients were evaluated by an independent researcher. RESULTS: Compared with the
one-year follow-up, the number of continent women remained the same, but a
significantly greater number of patients worsened. Forty per cent of the women
stayed in the same category of severity, while 45% moved into the contiguous
categories. The weekly frequency of wet episodes increased significantly, with a
mean increase of 2.65 episodes. Women with mixed incontinence were especially
prone to relapse in the long-term. Compliance with the exercises had a positive
influence on the outcomes, with 67% of the women expressing satisfaction with the
results. CONCLUSIONS: Despite a decline in the effect of conservative treatment
in the long-term, the majority of the women are satisfied with their treatment.
Patient compliance is the key to long-term success.
PMID- 10198480
TI - Evaluation of death registers in general practice.
AB - BACKGROUND: General practitioners (GPs) do not routinely receive information
about the deaths of those patients whose death certificates they have not
completed. We developed and evaluated a system for producing death registers for
GPs. AIM: To evaluate GPs' and practice managers' views on, and uses of, the
death register. METHOD: General practitioners in Newcastle (n = 161) and
Sunderland Family Health Service Authority (n = 144) areas were sent a
questionnaire on their sources and use of information about patients' deaths.
Death registers were sent to Newcastle practices; Sunderland practices were the
control group. A follow-up questionnaire was sent to Newcastle (n = 173) and
Sunderland (n = 140) GPs after two years. Newcastle practice managers (n = 45)
were interviewed after their practice had received death registers for one year.
RESULTS: Ninety-two per cent of Newcastle responders had seen the death register.
Seventy-three per cent saw it regularly. Of those who saw it, 92% found it useful
for communication within the primary health care team, bereavement follow-up, and
administration and medical audit. One fifth of GPs named the death register as
their first source of information about their patients' deaths. Newcastle GPs
reported greater levels of change in use of patient death information than the
control group. Practice managers circulated, used, and recorded information from
the death register. CONCLUSION: Death registers are valued and have demonstrable
benefits with regard to administration, bereavement care, and medical audit.
PMID- 10198481
TI - Assessment of management in general practice: validation of a practice visit
method.
AB - BACKGROUND: Practice management (PM) in general practice is as yet ill-defined; a
systematic description of its domain, as well as a valid method to assess it, are
necessary for research and assessment. AIM: To develop and validate a method to
assess PM of general practitioners (GPs) and practices. METHOD: Relevant and
potentially discriminating indicators were selected from a systematic framework
of 2410 elements of PM to be used in an assessment method (VIP = visit instrument
PM). The method was first tested in a pilot study and, after revision, was
evaluated in order to select discriminating indicators and to determine validity
of dimensions (factor and reliability analysis, linear regression). RESULTS: One
hundred and ten GPs were assessed with the practice visit method using 249
indicators; 208 of these discriminated sufficiently at practice level or at GP
level. Factor analysis resulted in 34 dimensions and in a taxonomy of PM.
Dimensions and indicators showed marked variation between GPs and practices.
Training practices scored higher on five dimensions; single-handed and dispensing
practices scored lower on delegated tasks, but higher on accessibility and
availability. CONCLUSION: A visit method to assess PM has been developed and its
validity studied systematically. The taxonomy and dimensions of PM were in line
with other classifications. Selection of a balanced number of useful and relevant
indicators was nevertheless difficult. The dimensions could discriminate between
groups of GPs and practices, establishing the value of the method for assessment.
The VIP method could be an important contribution to the introduction of
continuous quality improvement in the profession.
PMID- 10198482
TI - Why patients consult when they cough: a comparison of consulting and non
consulting patients.
AB - BACKGROUND: Although it is the commonest symptom presented to general
practitioners (GPs), little is known about why someone decides to consult with a
cough. AIM: To describe the illness behaviour of patients with a cough. METHOD:
Patients who had consulted a GP because of a cough, and a group of subjects who
had recently had a cough but had not consulted, were interviewed in a qualitative
study that investigated how they made sense of their illness. RESULTS: Consulting
patients understood their cough to be abnormally severe, whereas non-consulting
subjects regarded their cough as 'normal' and mild. Consulting patients thought
the cough would interfere with social roles and non-consulting subjects did not.
The consulting patients were much more likely to be worried about the cough than
the non-consulting subjects. In particular, half of the consulting patients were
worried about their hearts, whereas the non-consulting subjects were not. The two
groups did not distinguish bacteria from viruses, and did not differ in beliefs
about the role of antibiotics that they thought were needed for severe coughs.
Both groups had concerns about pollution. CONCLUSIONS: For consulting patients,
cough breached the taken for granted property' of health that the non-consulting
subjects with a cough were able to maintain. Cough, for the consulting patients,
was not a trivial illness.
PMID- 10198483
TI - The career outcomes for doctors completing general practice vocational training
1990-1995.
AB - BACKGROUND: While much has been published about the career outcomes of doctors
who completed general practice vocational training prior to 1990, no evidence is
currently available about those who have qualified since that time. AIM: To
obtain information about the career paths of doctors who had completed general
practice vocational training since 1990, and to compare the results with
previously published data. METHOD: Postal questionnaire survey of all doctors
completing vocational training during the period 1990-1995 in three regions of
the United Kingdom. The study examined current work status, career path since
completion of training, desire for and experience of part-time training, degree
of difficulty in choosing and following a career, and the degree to which certain
factors impeded career choice. RESULTS: The overall response rate was 64.8%,
although there was a significant difference between the response rates for men
and women. While virtually all responders were employed, with the majority
working in general practice, women were significantly less likely than men to be
working as principals in general practice, for all cohorts. These results were
very similar to those cohorts described in earlier studies. The career paths of
doctors only became stable after about four years. Of those working in general
practice, about 20% found it difficult to choose their career, and about 10%
found it difficult to follow their career. Out-of-hours work was the major factor
impeding career choice. CONCLUSION: Although they are taking longer to reach, the
final career destinations of doctors completing vocational training since 1990
are no different from those of earlier cohorts.
PMID- 10198484
TI - Potential for suicide prevention in primary care? An analysis of factors
associated with suicide.
AB - BACKGROUND: General practitioners (GPs) need to be aware of the risk factors for
suicide. GP records may provide clues to identifying the relative importance of
such risk factors. AIMS: To identify, in suicide cases and matched controls, the
patterns of consultation, diagnosis, and treatment of mental illness, and
recording of risk factors for suicide. To examine the usefulness of data
routinely collected by GPs in computerized databases to investigate treatment of
patients in general practice prior to suicide. METHOD: Case control study using
GP records from the General Practice Research Database (GPRD). Three controls
selected for each case, matched for age, sex, and duration of registration with
practice. Information extracted of the prevalence of major disease; diagnosis of,
and treatment, or referral for, mental illness; frequency of recording of recent
life events; and consultations with the GP in the 12 months prior to death.
RESULT: Of the 339 suicide cases recorded, 80% were male, which is similar to the
national percentage for this age group. Females were more likely than males to
have a history of mental illness and to have been diagnosed and treated for
mental illness in the 12 months before death (59% versus 35%), and women were
more likely to have previously attempted suicide (47% versus 27%). There was no
significant difference between males and females in period of time since last
contact with GP practice, but females consulted more frequently. Twenty-nine per
cent of cases had not consulted their GP in the six months prior to death. In
multivariate analysis, the following were identified as independent risk factors:
history of attempted suicide; untreated serious mental illness (odds ratio > 20);
recent (past 12 months) marital life event; alcohol abuse; frequent consultations
with GP; and previous mental illness. Recording of life events by GPs was poor.
CONCLUSIONS: Females at risk of suicide are more likely than males to have been
diagnosed and treated for mental illness. It is likely that GPs are under
diagnosed and under-treating males at risk. Data from the GPRD give comparable
results to those from other studies. The GPRD is a potentially useful tool for
research into relatively uncommon events in general practice.
PMID- 10198485
TI - The UMDS MSc in general practice: attainment of intended outcomes.
AB - BACKGROUND: The United Medical and Dental School's (UMDS's) MSc in general
practice is one of the longest running courses of its kind. Although descriptive
accounts of such courses have been published, little is known about their
outcomes. AIM: To measure the extent to which graduates feel they have personally
achieved 16 intended outcomes derived from the course objectives, and to record
current academic activities, particularly teaching and research. METHOD: A postal
questionnaire to graduates of the UMDS MSc in General Practice. RESULTS: The
response rate was 93%. Of the 71 responders, 23 have gone on to register for or
complete other degrees or diplomas. Over two-thirds of responders had an academic
commitment following the MSc. Two-thirds were currently engaged in research and
over half reported having had work accepted for publication. The majority of
graduates confirmed the attainment of all 16 outcomes, although outcomes related
to personal achievements were endorsed more strongly than those related to
service delivery. CONCLUSION: UMDS graduates are making a significant
contribution to their discipline and are unanimous in describing the course as an
important event in their personal development. As a result of this study, the
course organizers are seeking to increase the links between academic study and
everyday practice.
PMID- 10198486
TI - Can patients predict which consultations can be dealt with by telephone?
AB - The use of telephone consultations to reduce the workload of general
practitioners is well established both in this country and abroad. The principal
aim of this study was to discover the proportion of consultations currently
carried out in the surgery that would be suitable, for both doctor and patient,
to be managed over the telephone. The second aim was to establish what proportion
of such consultations could be predicted.
PMID- 10198487
TI - General practitioner prescribing of antibiotics for asthma.
AB - Although asthma management guidelines in New Zealand do not advise prescribing
antibiotics, almost a quarter of asthma consultations result in a prescription
for antibiotics. This study, as part of a repeat audit of asthma care at an after
hours medical centre, describes general practitioners' perspectives on
prescribing antibiotics to patients presenting with asthma. The results show that
GPs have tended to overestimate the risk of bacterial infection in such patients.
PMID- 10198488
TI - A community survey of patients with atrial fibrillation: associated disabilities
and treatment preferences.
AB - BACKGROUND: Anticoagulants are effective in preventing stroke in those with
atrial fibrillation, but most patients remain untreated. AIM: To investigate the
prevalence of disability, cognitive impairment, and problems with compliance in a
representative sample of the elderly with atrial fibrillation, and to determine
whether they would want treatment and how they would like services to be
arranged. METHOD: In a survey of a random sample of 4843 elderly subjects, those
with atrial fibrillation were identified using electrocardiograms. Views on
treatment were obtained using a structured interview. Disability was assessed
using the Office of Population Censuses and Surveys Disability Scale and
cognitive status using the Mini Mental State Examination. General practitioners
were asked, via questionnaire, for their views on each subject's compliance.
RESULTS: Two hundred and seven elderly people with atrial fibrillation were
identified. Almost all subjects expressed a willingness to undertake treatment to
prevent stroke and preferred blood testing performed outside of hospital.
Disability (82.7%), cognitive impairment (25.7%), and problems with compliance
(25.0%) were common, but the prevalence of these difficulties was not
substantially different from the general elderly population, and in many cases
they could be overcome (e.g. only 10% of subjects had problems with compliance
and no-one who could help them to comply). CONCLUSIONS: Most elderly people with
atrial fibrillation would accept treatment to prevent stroke. Disability,
cognitive impairment, and problems with compliance may make it difficult to treat
this patient group. An increase in the use of anticoagulants should be
accompanied by the development of services appropriate to this frail population.
PMID- 10198489
TI - Tackling alcohol misuse: opportunities and obstacles in primary care.
AB - Alcohol misuse is a major public health issue. Primary care has been recognized
as an ideal setting for the health promotional activity needed to reduce the
general population's alcohol consumption. This paper explores the background to
the current belief that primary care is suitable for this work by examining the
evidence of the potentially successful interventions the general practitioner
(GP) can undertake with alcohol misusing patients, GPs' attitudes towards this
work, and the impediments that exist. Computer searches of the MEDLINE database
up to 1997 and a manual literature search of the bibliographies of published
papers that were identified as relevant were carried out. Research points to GP
interventions being effective, but it also provides evidence of their negative
attitudes. It concludes that more training and support from local services are
needed if primary care is to meet its rich potential.
PMID- 10198490
TI - Time for a change? The process of lengthening booking intervals in general
practice.
AB - Longer booking intervals between appointments in general practice are generally
seen as 'a good thing', and have a strong 'evidence base' to support them.
Changing to longer booking intervals is regarded as a pipe dream by many general
practitioners (GPs). This paper reports the process and outcomes of a change to
longer booking intervals in one practice, identifies the key elements of the
change, and examines lessons learned for the practice, to help other practices to
do similarly. The most important factor in bringing about change was the
influence of facilitation by outside parties; first, by management consultants
who identified solutions to the practice's problems, and secondly, by recruitment
to a research study. Other outside influences were an awareness of the success of
other practices in changing to 10-minute booking intervals, and the increasing
'evidence base' to support such change. Internal influences on the process were a
desire to change as a result a perception that the practice was under-performing,
and the stress associated with this. As a result of the change, the number of
doctor consultations fell and the number of nurse consultations rose, fewer
patients reconsulted, and marginal improvements were reported on doctor and
patient satisfaction. Other practices may benefit from such change; the use of
management consultants as facilitators may instigate such change.
PMID- 10198491
TI - Women's attitudes to the development of midwifery group practices.
PMID- 10198492
TI - The RCGPs' questionnaire for measuring SHOs' satisfaction with hospital training.
PMID- 10198493
TI - Developing, validating and consolidating the doctor-patient relationship.
PMID- 10198494
TI - Acupuncture in smoking cessation.
PMID- 10198495
TI - Impact of guidelines for the diagnosis of UTI.
PMID- 10198496
TI - Osteoporosis in patients attending a fracture clinic.
PMID- 10198497
TI - Antibiotics for respiratory tract symptoms in general practice.
PMID- 10198498
TI - Forty-seven minutes a year for the patient.
PMID- 10198499
TI - Dietary advice for acute diarrhoea in general practice: a pilot study.
AB - BACKGROUND: Although there is no evidence that diet shortens acute diarrhoea,
doctors tend to give dietary advice. AIM: To test the effects of eating and
drinking normally on the duration of acute diarrhoea and on the feeling of well
being. METHOD: Randomized single-blinded, controlled trial in urban and semi
urbanized areas. Patients aged 3-70 years suffering with diarrhoea at least three
times on the preceding day, lasting no more than five days, were eligible. Two
regimes were randomly allocated to practices. In the intervention group, the
advice was to eat everything one liked and to drink more. The control group was
advised to follow a strict regime of fasting for 24 hours and was subsequently
given specified limitations. RESULTS: No significant differences between the 44
patients in the intervention group and the 27 in the control group were found for
the duration of watery diarrhoea (median 14 versus 13 hours), or the total number
of evacuations (2 versus 2.5). Among the items concerning well-being, only nausea
(51% versus 23%) showed a significant difference. CONCLUSION: In this pilot
study, the null hypothesis that both treatments will show equal results cannot be
confirmed or rejected because of the small number of participants. Despite our
efforts, we included fewer patients than expected. This might be due to the data
forms, which were rather complicated and voluminous for both, including doctors
and participants.
PMID- 10198500
TI - Understanding patient-initiated frequent attendance in primary care: a case
control study.
AB - BACKGROUND: Frequent attendance, which accounts for a high proportion of the
general practitioner's (GP's) workload, is still poorly understood. AIM: To
assess the association and impact of exposure to chronic physical illness, mental
disorders, life stress, and sociodemographic factors on the frequent attendance
of primary health care medical services. METHOD: Nine general practices in
Bizkaia, Spain, participated in a case-control study. Cases were patients who
exceeded the 90th percentile in the distribution of the number of visits that
they made on their own initiative from January 1993 to March 1994. Controls were
those for whom a single, patient-initiated consultation was registered. A total
of 102 cases and 100 controls were selected by stratified sampling proportional
to the size of each practice. We estimated odds ratios and population
attributable fractions for frequent attendance in relation to being exposed to
the study variables, adjusted by demographic characteristics by means of logistic
regression analysis. RESULTS: Medium-high life stress (adjusted odds ratio (AOR)
= 4.5, 95% confidence interval (CI) = 1.7-12.8), chronic physical illness (AOR =
3.1; 95% CI = 1.4-6.9), mental disorder (AOR = 2.5; 95% CI = 1.3-5.1), and age
were associated with patient-initiated frequent attendance. The adjusted
population attributable fraction for chronic physical illness was 41%, 30.9% for
mental disorder, and 15.2% for life stress. CONCLUSION: There is evidence that
patient-initiated frequent attendance is related to genuine physical and
psychosocial needs; therefore, recognition requires a bio-psychosocial approach
on the part of GP.
PMID- 10198501
TI - An analysis of referral patterns for dizziness in the primary care setting.
AB - BACKGROUND: The majority of balance disorders are non life-threatening and
symptoms will resolve spontaneously. However, some patients require further
investigation and many disorders may benefit from specialist treatment it is
unclear whether appropriate identification and referral of this group of patients
presently occurs. AIM: To review the management of patients with symptoms of
dizziness within primary care. METHOD: A retrospective review of the management
of 503 patients who visited their general practitioner (GP) complaining of
dizziness between August 1993 and July 1995. Management was then compared with
local criteria. RESULTS: On average, 2.2% of patients per year at the practices
studied consulted their GP about dizziness, amounting to 0.7% of all
consultations. The most common GP diagnosis was of an ear, nose, and throat (ENT)
disorder (33.8%). Similarly, many of the 16% referred were directed to ENT (36%)
specialists. The proportion of patients referred was significantly higher in
those seeing their GP at least twice, those with symptoms lasting a year or more,
or where there were additional symptoms associated with the dizziness, indicative
of a cardiac, ENT, or neurological disorder. Compared with the local criteria,
17% of management decisions were deemed inappropriate. The major failing was not
referring appropriate patients. This group comprised patients with chronic, non
urgent symptoms, and were significantly older than those appropriately referred.
CONCLUSION: Patients with chronic symptoms of dizziness, particularly the
elderly, are under-referred for specialist consultation and, therefore, do not
have access to appropriate treatment regimes. This suggests a need for further
training of GPs and evaluation of therapeutic needs of elderly dizzy patients.
PMID- 10198503
TI - Unwelcome customers? The epidemiology of removal from general practitioner lists
in Sheffield.
AB - BACKGROUND: The 1990 contract and the 1991 fundholding scheme encouraged
speculation that general practitioners (GPs) may remove patients from their lists
for financial reasons. Despite assertions that patient removals are increasing,
little evidence exists on the number or trends in removals. AIM: To describe the
epidemiology of removals by time, place, and person, and to determine whether
removals have increased in recent years. METHOD: Descriptive analysis of routine
data relating to all removals of Sheffield residents from GP lists during 1991
1996. RESULTS: Removal from a doctor's list was a rare event (2.4 per 1000
patients per year) that did not become more common over the period examined.
Removal rates varied by age, sex, and practice, with relatively high rates among
children, young women, and the over-75s. There was a significant tendency for
higher removal rates in more deprived parts of the city. CONCLUSION: Removal
rates have not increased in Sheffield. The reasons for the variation in rates by
age, sex, and practice are unknown. The higher rates noted in the under-fives and
young women are consistent with the possibility that the 1990 target payment
scheme may have increased removal rates in these age groups.
PMID- 10198502
TI - Deliberate departures from good general practice: a study of motives among Dutch
general practitioners.
AB - BACKGROUND: When general practitioners (GPs) act contrary to their own standards
of good practice, they usually cite patient demands as the main reason. However,
up until now, studies have relied on doctors' recollections of departures from
their own norms, which may be unreliable. AIM: To systematically explore GPs'
motives for deliberate departures from their own conception of good practice.
METHOD: Forty-nine GPs, over five days, registered to what extent they had
deviated from their own norms, and recorded the motives underlying any deviation.
RESULTS: Of the 6087 consultations registered, 10% contained some departure from
'good' general practice, the majority (75%) of which was perceived by the doctor
concerned as 'slight'. Doctors underpinned their departures mostly by referring
to the doctor-patient relationship: the wish to be nice was used, on average, in
42% of deviations, and the wish to prevent a conflict in 30%. The most important
non-relational motive was clinical uncertainty, which doctors used in 11% of
their cases. DISCUSSION: Contrary to common belief, GPs often comply with patient
requests because they wish to, and not because they feel forced to. Whether or
not this behaviour affects the quality of care is largely dependent on the model
of 'good' general practice used.
PMID- 10198504
TI - The effects of detection and treatment on the outcome of major depression in
primary care: a naturalistic study in 15 cities.
AB - BACKGROUND: This study reports the responses of patients with confirmed
depressive illnesses to different treatments in the WHO Mental Disorders in
General Health Care study, conducted in 15 cities around the world. AIM: To
discover how depressions recognized by the doctor compare with unrecognized
depressions, both in terms of the initial illnesses and their outcomes, and to
compare the outcomes of those depressions treated with antidepressants with those
treated with daytime sedatives. METHOD: The design of the study was naturalistic,
in that physicians were free to treat patients however they wished. Patients with
confirmed depressive illnesses were assigned to four groups: treatment with an
antidepressant; treatment with a daytime sedative (usually a benzodiazepine);
patients recognized as having depression by the physician but were not offered
drug treatment; and patients unrecognized as having depression by their
physician. RESULTS: Both groups receiving drugs had illnesses of equal severity,
were demographically similar to one another, and had similar previous histories
of depression. Those receiving antidepressants had significantly fewer overall
symptoms and fewer suicidal thoughts than those treated with sedatives. By the
end of one year, differences between the groups had disappeared: patients not
given drugs had milder illnesses but did significantly better than those
receiving drugs, both in terms of symptoms lost and their diagnostic status.
Unrecognized depressions were less severe than recognized depressions, and had a
similar course over the year. CONCLUSIONS: Patients receiving antidepressants
were better in terms of overall symptoms and suicidal thoughts than those treated
with sedatives at three months, but this advantage does not persist. Depression
emerges as a chronic disorder at one-year follow-up--about 60% of those treated
with drugs, and 50% of the milder depressions, still meet criteria for caseness.
The study does not support the view that failure to recognize depression has
serious adverse consequences, but, in view of the poor prognosis of depression,
measures to improve compliance with treatment would appear to be indicated.
PMID- 10198506
TI - The implementation of evidence-based medicine in general practice prescribing.
AB - BACKGROUND: Research on the implementation of evidence-based medicine has focused
on how best to influence doctors through information and education strategies. In
order to understand the barriers and facilitators to implementation, it may also
be important to study the characteristics of those doctors and practices that
successfully implement evidence-based changes. AIM: To determine the relationship
between practice and doctor characteristics and the implementation of recommended
evidence-based changes in the area of prescribing. METHOD: Visits were made to 39
practices in southern England. Audits of three key prescribing changes were
carried out and amalgamated to produce an 'implementation score' for each
practice. These scores were related to a wide range of practice and doctor
variables obtained from a questionnaire survey of doctors and practice managers.
RESULTS: There was wide variation between the practices' implementation scores
(mean 67%, range 45% to 88%). The only factors that had a significant
relationship with implementation of these important prescribing changes were an
innovative approach among the doctors (most practitioners were cautious of
change), and fundholding status. Use of clinical protocols, disease registers, or
computers was not associated with overall implementation score, nor was the
doctor's age. Doctors complained of information overload. CONCLUSIONS: The
emphasis on the need for evidence in medicine, and better transmission of
information, needs to be balanced by a recognition that most general
practitioners are pragmatic, averse to innovation, and already feel overwhelmed
with information. Important advances in therapy may be crowded out. More
attention should be given to the facilitation of priority changes in practices.
PMID- 10198505
TI - Randomized controlled trial of teaching practice nurses to carry out structured
assessments of patients receiving depot antipsychotic injections.
AB - BACKGROUND: A third of patients with schizophrenia are out of contact with
secondary services. Many of these patients receive maintenance medication as
depot antipsychotics from practice nurses, most of whom have negligible training
in mental health. AIM: To examine the impact of a structured assessment on the
process of care and clinical status of schizophrenia patients by practice nurses
who received a one-day training course. METHOD: All identified patients were
randomly allocated to structured assessments and outcome, measured by the number
of assessments and the changes in care recorded in primary care notes. A
comprehensive assessment of clinical and social functioning and level of unmet
need in intervention and control patients was carried out after one year by an
independent researcher. RESULTS: A high rate of consultation and clinical need in
this patient group was demonstrated. Practice nurses were more diligent in
carrying out assessments than general practitioners (GPs), but there was no
impact on treatment patterns or clinical outcome. CONCLUSIONS: Structured
assessments by practice nurses are feasible with this patient group, but
training, targeted at both nurses and GPs, is needed if this intervention is to
translate into health gain.
PMID- 10198507
TI - An evaluation of quality control activity for near patient testing in primary
care.
AB - Near patient activity is now increasing within the United Kingdom and can be a
valuable activity within primary care, but only within the confines of safe
practice that incorporates quality control procedures. This study identified
widespread use of near patient testing (NPT) within primary care but that there
is a haphazard approach to specific test performance. Results showed a poor
understanding of quality control issues and provide a clear indication of future
training and educational priorities if NPT is to develop in primary care.
PMID- 10198508
TI - Relationship between new and return consultations and workload in general
practice.
AB - General practitioners (GPs) in Tayside, with higher weekly surgery workloads,
tended to have a greater proportion of return consultations compared with GPs
with smaller workloads. By reducing the number of return consultations, GPs could
have a notable effect on their workload and alleviate the, oft-quoted, stress
induced by the perceived increase in demand for patient care.
PMID- 10198509
TI - GP frequent consulters: their prevalence, natural history, and contribution to
rising workload.
AB - A small proportion of patients use a disproportionate amount of general
practitioners' (GPs') time. We demonstrate here that such frequent attending
behaviour tends to persist through five-year follow-up, suggesting the need for
the development of specific management strategies. We also show that, at any rate
in one practice, total workload is increasing dramatically, and that frequent
consulters make up a large part of the increase.
PMID- 10198510
TI - Repeat dispensing by community pharmacists: advantages for patients and
practitioners.
AB - Repeat prescribing is an appreciable chore for general practitioners (GPs), and
often lacks rigorous clinical control. This paper reports on a pilot repeat
dispensing system, which employed community pharmacists to streamline the process
and provide clinical supervision. The system described operated within the
current regulations, was popular, and worked well for patients on stable
treatment regimes.
PMID- 10198511
TI - Antibiotic treatment of acute otitis media in children under two years of age:
evidence based?
AB - BACKGROUND: Appropriate use of antibiotics is one of the major issues in medicine
today. In most countries, acute otitis media in children is treated with
antibiotics; however, the efficacy of antibiotic use in every acute otitis media
is a controversial issue. It may be worthwhile looking for special risk groups
that benefit more from antibiotic treatment for acute otitis media. Children
under two years of age with acute otitis media are at risk of poor outcome. AIM:
To assess whether the current high prescription rates of antibiotics for acute
otitis media in children under two years of age (being a risk group for poor
outcome) are based on an established increased efficacy. METHOD: Systematic
literature review and a quantitative analysis with an assessment of the
methodological quality of published trials, comparing antibiotic treatment with
non-antibiotic treatment in acute otitis media in children aged under two years.
RESULTS: Six trials were included. Trials from before 1981 had a poor
methodological quality. Four were suitable for the quantitative analysis. Only
two of them were truly placebo-controlled. Of these two, one included only
recurrent acute otitis media and the other included only non-severe episodes.
With these restricted data, no statistically significant difference was found
between antibiotic-treated children and controls under two years of age with
acute otitis media, judged on the basis of clinical improvement within seven days
(common odds ratio = 1.31; 95% CI = 0.83-2.08). CONCLUSION: The current high
prescription rates of antibiotics among children under two years of age with
acute otitis media are not sufficiently supported by evidence from published
trials. New randomized placebo-controlled trials using reliable methodology are
needed in this young age group.
PMID- 10198513
TI - GPs' continuing medical education.
PMID- 10198514
TI - North West Region Research Practice Initiative: a general practitioner's
perspective.
PMID- 10198515
TI - Triage of same day consultations.
PMID- 10198512
TI - Reducing antibiotics for respiratory tract symptoms in primary care:
consolidating 'why' and considering 'how'.
AB - We summarize recently published evidence showing that antibiotic treatment offers
little or no benefit to most patients presenting with sore throats, acute otitis
media, maxillary sinusitis, and acute bronchitis. Despite this research, the
prescription of antibiotics for respiratory tract conditions is rising in
Britain. This wastes money, encourages people to consult for self-limiting
conditions, and causes bacteria to become resistant to antimicrobials. Ways of
changing present practice are underresearched. Enhanced consulting skills,
guidelines and monitoring strategies, patient education, and anti-inflammatory
drugs for recurrent and chronic sufferers all hold promise.
PMID- 10198516
TI - Recruitment for drug trials.
PMID- 10198517
TI - Use of alternative treatments by patients with psoriasis.
PMID- 10198518
TI - Oral contraception and health: what do GPs monitor?
PMID- 10198519
TI - Estimation of 3D location and orientation of human vertebral facet joints from
standing digital radiographs.
AB - This study provides a biplanar radiographic reconstruction method of volumes of
interest to evaluate the location, dimensions and orientation of human facet
joints. Visibility of facet anatomical landmarks and areas of interest was
evaluated on digital radiographs of 20 idiopathic scoliotic adolescents. Areas of
interest have provided the most reliable evaluation of facet joints on postero
anterior and lateral digital radiographs. Volumes of interest of a thoracic and
lumbar spinal segment (T1 to L3) were computed using the proposed biplanar 3D
reconstruction method and compared with serial tomographic reconstructed models.
Differences of 1.5 +/- 0.7 mm in 3D location and 1.8 +/- 1.2 degrees in sagittal
orientation of volumes of interest were observed between both representations.
This in vivo geometric information on human vertebral facet joints will help us
to understand their role in spinal disorders and will provide important data for
personalised biomechanical simulations.
PMID- 10198520
TI - Electrical impedance tomography reconstruction algorithm based on general
inversion theory and finite element method.
AB - A strict EIT reconstruction algorithm, the general inversion algorithm (GIA) is
presented. To improve the noise performance, the algorithm is modified by
attenuating the condition number of the forward matrix F and implemented using an
improved FEM scheme, to obtain the 2D image of impedance change (dynamic image).
This modified general inversion algorithm (MGIA) can be used on a larger
dimension FEM model (248 elements) and is more practical than the GIA. When
implementing this algorithm in computer simulation and in a physical phantom, it
is found that the MGIA has a smaller reconstruction error than the currently used
algorithms (equipotential-back-projection algorithm and filtered spectral
expansion algorithm). With 0.1% white noise in the data, the algorithm can still
reconstruct images of a complicated model. Further improvements are also
discussed.
PMID- 10198521
TI - EEG coherence and reference signals: experimental results and mathematical
explanations.
AB - Coherence has become an essential tool in the description of functional
relationships between EEG signals generated within various brain areas. In EEG
coherence analysis, the reference signal has an important influence, as an
improper reference can distort the results and make them impossible to interpret.
In the study, EEG are recorded from one volunteer in 11 sessions, with electrodes
selected according to the international 10-20 system against FCz. Additional
electrodes are placed on the nose, chin and left and right ear lobes, and
recordings are made also against FCz. This enables re-referencing of the stored
EEG signals for different reference sites, averaged reference signals, common
average reference, Laplacian and bipolar. Coherence values using single reference
electrodes depend on the reference site to a large extent. Reliable results are
obtained using averaged non-cephalic signals as reference ([A1 + A2]/2).
Coherence based on FCz yields slightly lower or higher values than that based on
non-cephalic reference sites. Completely different results yield common average
reference recordings, Laplacian and bipolar recordings, probably owing to the
cancellation effect of essential signal portions using these techniques. A
mathematical model for coherence based on signal-to-noise ratios is introduced to
explain the experimental findings: the model demonstrates that noisy reference
signals lead to coherence increase, whereas a coherent amount in the reference
signal leads to coherence decrease.
PMID- 10198522
TI - Evoked potential estimation using modified time-sequenced adaptive filter.
AB - A method called modified time-sequenced adaptive filtering (MTSAF) is applied to
estimate evoked potential (EP) signals and track the temporal variations of EPs.
The MTSAF consists of a set of adaptive filters (AFs), with each processing a
time segment of EP data. After convergence, each AF reaches the best estimation
of EP signals over its own time segment in terms of minimum mean squared error
(MMSE). Numerical results of simulated and human EP data show that the MTSAF
reaches better estimation of EPs than a conventional adaptive signal enhancer
(ASE). With the MTSAF, the temporal variations of EPS across trials can be
estimated to reveal more subtle variations of EPs, which may be of clinical
value.
PMID- 10198523
TI - Brain evoked potential topographic mapping based on the diffuse approximation.
AB - Evoked potential mapping is a convenient technique to describe brain electrical
activity using pictorial representation. A new interpolation method based on the
diffuse approximation is applied to represent evoked potential distribution over
the skull. The method retains most of the attractive features of the finite
element method but does not require explicit elements. In the simulation
examples, the human head is assumed to be a single-layer sphere with homogeneous
conductivity, and Ary eccentricity transformation is considered to approximate
the more realistic three-shell model. The patterns shown in the computed maps
suggest the ability of the proposed method to extract coherent information from
the data from different electrodes. In the application protocol, visual evoked
potentials are used to test the method with a realistic head shape.
PMID- 10198524
TI - Force-current relationships in intraneural stimulation: role of extraneural
medium and motor fibre clustering.
AB - Animal experiments and model simulations of monopolar, intrafascicular nerve
stimulation are presented to study force-current relationships (recruitment
curves). The conductivity of the extraneural medium is of prime importance to the
resulting recruitment cures: an insulating extraneural medium generally leads to
steeper curves with lower threshold currents than a well-conducting extraneural
medium. Extensive statistical comparison of experimental and model results
suggests the occurrence of clustering of alpha-motoneurons within the fascicle,
manifesting itself mainly by an increased spread in threshold currents, as
opposed to the situation where the fibres are distributed uniformly throughout
the entire fascicle.
PMID- 10198525
TI - Development of a cardiac acoustic mapping system.
AB - The authors describe a cardiac acoustic mapping system designed to acquire,
analyse, and display the amplitude distribution of a phonocardiogram (PCG)
recorded from 22 sites on the thorax. A new PCG envelope detection approach,
implemented by analogue circuits, enables simultaneous sampling of PCG envelopes
from the 22 sites at a rate of 250 Hz/channel. A calibration procedure removes
channel-to-channel gain variations, and a coherent averaging of each PCG envelope
over several cardiac cycles improves the signal-to-noise ratio. Time congruent
samples from the 22 averaged PCG envelopes are then interpolated in 2D to
generate the isoamplitude maps. Preliminary results show that the acoustic maps
can help locate the source of heart sounds and murmurs, and characterise their
radiation and propagation patterns. Cardiac acoustic mapping opens up new avenues
for the study of the propagation of heart sounds and murmurs through the heart
thorax acoustic system. This technique could contribute to improvements in the
diagnosis of valvular dysfunctions.
PMID- 10198526
TI - Recovery of beat-to-beat variations of QRS.
AB - There is a growing interest in the analysis of beat-to-beat variations of the
morphology (BBM) of cardiac waves in electrocardiograms (ECG). Such analyses are
confronted with the low BBM-to-noise ratio. An ECG clustering technique is
introduced that brings the benefits of signal averaging to BBM analysis and
recovers the beat-to-beat pattern of BBM. ECG clustering aligns waves and sorts
them into clusters. The precision of the alignment was enhanced by sub-sample
alignment. Kohonen's self-organising neural networks identified the clusters of
the cardiac waves during training. The subsequent clustering of a wave results in
a label for the closest cluster, a distance to the cluster and optimal alignment.
Furthermore, ECG clustering avoids base-line variations and amplitude modulation
sufficiently to be applied to the QRS wave in the raw ECG. The technique is
demonstrated on 14 subjects with coronary heart disease and no myocardial
infarction, myocardial infarction, or inducible ventricular tachycardia. ECG
clustering is a general-purpose technique for beat-to-beat analysis, where the
variations are cyclic as in the sinus rhythm. Results show that beat-to-beat
variations in the QRS morphology are in general cyclic, with a main period of
about four cardiac cycles. All calculations were performed with the Cardio
software.
PMID- 10198527
TI - Principal component analysis of chest wall movement in selected pathologies.
AB - A method is presented for assessing a compact set of parameters characteristic of
respiratory system functional status. 3D movements of points in the chest wall
and the volumes of chest wall compartments (pulmonary rib cage, abdominal rib
cage and abdomen) are considered. The co-ordinates of these points are measured
using an opto-electronic system for 3D motion analysis. Principal component
analysis is applied to these data. The behaviour of the eigenvectors of the
covariance matrix of the 3D co-ordinates of the points on the chest wall shows
close agreement with the pathology characteristics. The same is found for the
percentage of total variance explained by the principal components of the volume
variations. In this case, the higher values of variance percentage explained
indicate independent motions (active or passive) in the degrees of freedom of the
system identified by partitioning the total volume into compartments.
PMID- 10198528
TI - Comparison of multipole and mean value methods to quantify dust in human lungs:
simulating the magnetopneumography procedure.
AB - Magnetopneumography (MPG) can quantify the retention of magnetisable particles in
the lung acquired, for instance, in welding work. MPG is non-invasive and is used
in occupational health, industrial hygiene and lung physiology. Following a brief
magnetisation, the remanent magnetic field is mapped with magnetometers outside
the thorax. There is no unique analytical inverse solution to this class of
magnetostatic problem, and various inverse methods have been proposed. In the
present study, the influence of variations in size and shape of the lungs and
chest, magnetic measurement noise, positional noise and spatial dust distribution
are investigated in five inverse methods. The mean value of the field map,
calibrated against a lung phantom, is the commonly used method. Lung and chest
size influence the mean value method solutions strongly. Correction for chest
size reduces these errors, but bias errors and sensitivity to the deposition
pattern remains a problem. A multipolar expansion, including dipolar, quadrupolar
and octopolar moments, yields best results overall, provided the single-to-noise
ratio is sufficient. This inverse solution is unbiased, requires no calibration
with phantom lung models and serves to minimise errors due to inter-individual
differences in anatomy and to inhomogeneous retention of inhaled dust.
PMID- 10198529
TI - Estimation of non-cardiogenic pulmonary oedema using dual-frequency electrical
impedance.
AB - The study investigates the effects of non-cardiogenic oedema, especially the
accumulation of protein in extracellular fluid, on thoracic impedance and
proposes a new method of oedema measurement based on an impedance ratio from a
dual-frequency measurement. In vitro measurements in a cell containing an albumin
in-saline solution yield a resistance increase when the albumin concentration
increases. Subsequently, 13 patients having acute respiratory failure are
measured. The single-frequency Z0 measurements and the proposed impedance ratio
are compared with extravascular lung water (EVLW) determined by the double
indicator dilution method. The single-frequency measurement correlates poorly
with EVLW (r = -0.24, p = 0.56). In some patients, a total thoracic impedance
increase is found with increasing EVLW. The correlation between the impedance
ratio and EVLW is r = -0.79 (p < 0.0005). The ratio decreases as EVLW increases.
Thus, when oedema is measured using bio-impedance, cardiogenic and non
cardiogenic oedema yield different results. It is well recognised that
cardiogenic oedema decreases total thoracic impedance. In non-cardiogenic oedema,
however, protein accumulation causes an impedance increase. The decrease in the
impedance ratio as EVLW increases can be explained by the accumulation of albumin
in the extracellular compartment.
PMID- 10198530
TI - Investigation into the effects of haematocrit and temperature on the resistivity
of mammalian blood using a four-electrode probe.
AB - Haematocrit and temperature effects on resistivity are investigated using the
electrical impedance method. Measurements are made extensively for pig's blood.
The experimental set-up basically involves four ring electrodes being placed
around a wooden probe that is subsequently immersed into a syringe containing
pig's blood. The syringe is then submerged in water maintained at a constant
temperature while measurements are taken. The resistivity of blood is found to
increase linearly by approximately 2.9% as the haematocrit level increases from
18% to 49% at a fixed temperature of 37 degrees C. Furthermore, the resistivity
is found to decrease linearly by approximately 22% with temperature increasing
from 33 degrees C to 42 degrees C for all practical levels of haematocrit.
PMID- 10198531
TI - Pulsewidth optimisation for transformer-coupled transcutaneous current pulse
generation.
AB - A general theoretical approach for the determination of the optimum pulsewidth
used for TENS/EMS/FES is presented. Analysis based on the interaction between a
step-up transformer-coupled nerve stimulator and an electrode-tissue load
modelled as a simple lossy capacitive load results in excellent agreement between
the predicted and measured performance. The analysis shows that, by adjusting the
pulsewidth (PW) of a push-pull symmetric square waveform such that PW = 4.5 tau,
the total charge delivered to the tissue load can be minimised without impacting
the efficiency of the nerve stimulation. Additionally, by minimising the charge
exchange supported portion of the current pulse, which is primarily responsible
for the pH shift and subsequent tissue burning with long-term use, the latter can
be reduced to an acceptable level.
PMID- 10198532
TI - Colonoscope flexural rigidity measurement.
AB - A testing device is developed that determines the stiffness, or flexural
rigidity, of an endoscope at specific locations down its length by subjecting it
to a compressive axial force, a situation similar to the actual forces applied to
the endoscope during a clinical procedure. The endoscope is made to deform in a
similar fashion to a slender buckled column and the force causing this
deformation is related to the flexural rigidity using column buckling theory. A
direct relationship between the critical load needed to cause buckling and the
square of column length L is demonstrated experimentally and is expected
theoretically, giving confidence in the application of column buckling theory to
endoscope testing. Additional confidence in the validity of the column buckling
test results is obtained by their similarity to data obtained by subjecting the
endoscope to a transverse load, determining deflection, and modelling the
endoscope as a bent elastic beam. Several makes and models of endoscopes were
tested, with flexural rigidity values typically ranging between 160 to 240 Ncm2.
The effect of a metal stiffener inserted in an endoscope's accessory channel is
quantified, as is the change in flexural rigidity down the insertion shaft of a
graded-stiffness endoscope. Significant differences in flexural rigidity were
obtained between identical endoscopes, each sharing similar usage histories,
indicating the need for flexural rigidity measurements for each individual
endoscope of a particular model line, though a more extensive study is required
to reliably determine scope-to-scope stiffness variations for a particular model
line.
PMID- 10198533
TI - Analytical relationship between arterial input impedance and the three-element
Windkessel series resistance.
AB - The recently proposed energy-balance method for estimating the series resistance
of the three-element Windkessel model is reformulated in the frequency domain.
New mathematical expressions are analytically derived, involving Fourier
harmonics of pulsatile arterial pressure and flow. It is shown that the series
resistance of the arterial three-element Windkessel model can be expressed as a
weighted sum of the arterial input impedance moduli.
PMID- 10198534
TI - Feature-based classification of myoelectric signals using artificial neural
networks.
AB - A pattern classification system, designed to separate myoelectric signal records
based on contraction tasks, is described. The amplitude of the myoelectric signal
during the first 200 ms following the onset of a contraction has a non-random
structure that is specific to the task performed. This permits the application of
advanced pattern recognition techniques to separate these signals. The pattern
classification system described consists of a spectrographic preprocessor, a
feature extraction stage and a classifier stage. The preprocessor creates a
spectrogram by generating a series of power spectral densities over adjacent time
segments of the input signal. The feature extraction stage reduces the
dimensionality of the spectrogram by identifying features that correspond to
subtle underlying structures in the input signal data. This is realised by a self
organising artificial neural network (ANN) that performs an advanced statistical
analysis procedure known as exploratory projection pursuit. The extracted
features are then classified by a supervised-learning ANN. An evaluation of the
system, in terms of system performance and the complexity of the ANNs, is
presented.
PMID- 10198535
TI - Implantable stimulation system dedicated for neural selective stimulation.
AB - A functional electrical stimulation system is presented, which is dedicated for
the selective neural stimulation of the bladder. The proposed system is composed
of an internal stimulator (implant) and an external controller. The system is
used to produce low-pressure voiding of the bladder in spinal cord injured
patients. The implant is powered and operated by the external controller via
radio-frequency electromagnetic coupling. All stimulation parameters are chosen
externally using the controller and are sent to the implant, which produces the
desired stimuli. These stimuli are applied directly to the S2 nerve which is
linked to the sphincter and bladder muscles. A high-frequency signal is used to
inhibit the contraction of the sphincter muscle, and low-frequency pulses
stimulate the bladder muscle (the detrusor). Dedicated computer software is used
by the physician to select the optimal parameters for each patient and to
activate the implant through a parallel port interface with built-in transmitter.
The parameters are then transferred to a hand-held controller which is used by
the technical staff and by the patients themselves. Acute studies have been
performed to validate the selective stimulation strategy, and chronic
experimentation is currently underway in dogs.
PMID- 10198536
TI - Electrically induced neurite outgrowth of PC12 cells on the electrode surface.
AB - Morphological differentiation of PC12 cells cultured on an indium-tin oxide (ITO)
electrode has been induced to grow neurites in the absence of nerve growth factor
(NGF) by electrical stimulation. Rectangular pulse wave potentials were applied
to the electrode at amplitudes of 200 mV and 400 mV with frequencies of 50 Hz,
500 Hz, and 1 kHz. The PC12 cells differentiated most prominently at 200 mV with
100 Hz. No statistically significant differences were observed among the
electrically induced neurite lengths. The electrically induced differentiation
was completely inhibited by a blockade of calcium influx using LaCl3. This
indicates that repeated potential shift in the vicinity of a cellular membrane
may stimulate morphological response, probably through calcium ion channels.
PMID- 10198537
TI - Comparative mitogenic potencies of EGF and TGF alpha and their dependence on
receptor-limitation versus ligand-limitation.
AB - Transforming growth factor alpha (TGF alpha) has been reported to be a more
potent agonist when compared to epidermal growth factor (EGF) in several systems
while acting via their common receptor, the epidermal growth factor receptor
(EGFR). It has been postulated that this increased potency is mediated by the
increased recycling of EGFR upon activation by TGF alpha as against receptor
activation by EGF. The authors test this hypothesis by simultaneously measuring
mitogenesis and the dynamics of surface receptor number in response to these
ligands in NR6 mouse fibroblasts expressing the EGFR. The data demonstrates that
increased receptor recycling due to endosomal dissociation of TGF alpha can
indeed realise an increased mitogenic potency relative to EGF under appropriate
cellular and experimental conditions (i.e. situations in which the increase in
the number of occupied receptors due to receptor sparing by TGF alpha represents
additional mitogenic signalling capacity). However, this difference in receptor
trafficking does not uniquely determine the relative potencies of these ligands
since TGF alpha is a less potent mitogen compared to EGF when experimental
conditions are dominated by the effects of ligand trafficking on growth factor
availability. Thus, the relative potencies of these growth factors are determined
in a given context by the relative importance of ligand and receptor trafficking
effects which determine the availability of these signalling components. These
results are consistent with a suggested model of hormone responsiveness which
favours dissociative ligands (such as TGF alpha) in receptor-limited situations
and non-dissociative ligands (such as EGF) in the case of ligand limitation.
PMID- 10198538
TI - Engineered erythrocytes: influence of P50 rightward shift and oxemia on oxygen
transport to tissues.
AB - The red blood cell (RBC) membrane may be reversibly opened using a lysis
resealing continuous flow method. The technology was adapted to the
internalisation of an allosteric effector of haemoglobin, Inositol-Hexaphosphate
(IHP). This molecule, occupying the allosteric site of 2,3 Bis-Phosphoglycerate
with a very large affinity, induces a rightward shift of the oxyhaemoglobin
dissociation curve (ODC). From ODC parameters in human volunteers, the potential
effect of P50 (oxygen pressure at 50% haemoglobin saturation) on oxygen
exchangeable fraction (OEF%), for various oxygen partial pressures (oxemia) was
evaluated. For hyperoxic or normoxic arterial oxygen pressure (paO2), rightward
shift greatly improved OEF%. In optimised conditions, engineered erythrocytes
were potentially able to deliver two to three times more oxygen than normal
cells. For patients with decreased paO2, as observed in chronic obstructive
pulmonary deficiency (COPD), the reduction in arterial oxygen saturation (saO2%)
reduces the benefit of the treatment for paO2 values between 60 and 80 mmHg.
Below 60 mmHg, the saO2% reduction cannot be compensated by a corresponding
reduction in svO2%, particularly for organs with physiologically low svO2%. In
these organs, deleterious effects could be observed for a very large rightward
shift of the ODC. Such engineered cells have unique properties for oxygen
transport improvement and may be used for the treatment of patients suffering
from diseases associated with hypoxia and ischemia.
PMID- 10198540
TI - Three-dimensional changes of the cytoskeleton of vascular endothelial cells
exposed to sustained hydrostatic pressure.
AB - The three-dimensional changes in the cytoskeleton and in cell proliferation of
bovine pulmonary artery endothelial cells when exposed to sustained hydrostatic
pressure were investigated in vitro using laser scanning confocal microscopy.
Subconfluent endothelial cells on rigid substrates were exposed to 1.5, 5 and 10
cm H2O pressure under hydrostatic heads of culture medium for up to seven days.
Confocal microscopic images were taken at distances of 0.4 micron through the
thickness of the sample and visualised in multiplanar, stereopair and 90 degrees
rotation formats. The results of the study provide evidence of: increased
proliferation after exposure to 10 cm H2O pressure for five and seven days; cell
bilayering after exposure to 1.5 and 5 cm H2O pressure and trilayering after
exposure to 10 cm H2O pressure for seven days; and F-actin filament
reorganisation into centrally located, parallel, stress fibres in confluent
cells, into peripheral bands in subconfluent, multilayered cells, and into
multilayers in the plane perpendicular to the applied force.
PMID- 10198539
TI - Rotating-wall vessels, promising bioreactors for osteoblastic cell culture:
comparison with other 3D conditions.
AB - Osteoblastic cells cultured on microcarriers in bioreactors are a potentially
useful tool to reproduce the in vivo three-dimensional (3D) bone network. The aim
is to compare different types of 3D and two-dimensional (2D) osteoblastic
culture. ROS17/2.8 cells are cultured in a bioreactor (rotating-wall vessel) or
in two kinds of control (3D petri dish, 3D Percoll) and on two types of
microcarrier (Cytodex 3 and Biosilon). Growth and morphology are determined by
cell count and SEM, and differentiation is determined by dosage of alkaline
phosphatase (ALP) activity and northern blots (ALP and osteocalcin (OC)). SEM
shows that Biosilon microcarriers are the best substrate. Proliferation in the
RWV and 3D petri dish is still in the exponential phase, whereas growth in the 2D
culture reaches a plateau after eight days of culture. ALP activity and the ALP
and OC mRNA levels are similar at day 8 for both the RWV and 3D petri dish.
However, at day 10, cells are more differentiated in the RWV. The study shows
that osteoblasts are both proliferate and differentiate in 3D structures. A BrDU
immunocytochemical approach shows that only the cells in the periphery of the
aggregates proliferate. Therefore the bioreactor may be a suitable tissue culture
model for investigation of growth and differentiation processes in tissue
engineering.
PMID- 10198541
TI - [Medicine based on evidence: a useful tool for the pediatric surgeon].
PMID- 10198542
TI - [Integrated treatment of cleft lip and palate. Organization of a treatment team].
AB - OBJECTIVE: Collect the team experience in the treatment of children with cleft
lip and palate, indicating the evolution of the team composition, advantages and
improvement aspects, trying to transmit the need of team treatment. METHOD: The
Bilbao cleft palate team was created in 1983, since then a cleft palate clinic, a
parents group and a unit of velopharyngeal function has been developed. At
present the team is composed by: pediatric reconstructor surgeon, speech
therapist, orthodontist, dentist, pediatrician, ENT, maxillofacial surgeon,
dismorphologyst, geneticist, nursing. RESULTS: One of the achievements has been
the data unification, obtaining speech cephalometrics, photographic dental casts
and video images with prospective view. At this time 403 cleft lip and palate
children have been intervened, being essential the transdisciplinar team approach
between surgeon, speech therapist and orthodontist. The importance of the team
coordinator is pointed. The results of an audit of the two stage cleft palate
closure in complete unilateral cleft lip and palate have obligated us to vary our
surgical policy. The unresolved aspects are the lack of multidisciplinary team
recognition at official level and the non existence of orthodontist in staff,
without cost coverage of this treatment by public health system. CONCLUSIONS: In
our experience the team treatment of cleft lip and palate has resulted in
improvement of the clinic results, treatment protocols and training.
PMID- 10198544
TI - [Hemodynamics and oxygenation in experimental lung lobe transplantation].
AB - INTRODUCTION: Lung transplantation is the only valid treatment for the severe
neonatal pulmonary hypoplasia. The objective of this work is to develop and to
establish a model of lobar lung transplantation. MATERIAL AND METHODS: Twenty
pigs were used. Neonates 2-3 weeks; adults 10-12 weeks. Donors weighed 15 to 20
kg and recipients 5 to 7. In Group A animals were used to assess surgical anatomy
and to develop surgical technique and instrumentation's model. The remainder
animals (Group B) underwent left lobar lung transplantation. Hemodynamic and
oxygenation data were collected before and after six hours of right lung
exclusion. RESULTS: All animals tolerated right lung exclusion. There was a
significant increase in mean pulmonary artery pressure and a sustained reduction
in cardiac output. Oxygenation values were not affected during unilateral lung
perfusion. CONCLUSIONS: The neonatal pig has a good tolerance to reduced-size
lung transplantation. Lobar lung transplantation could increase substantially the
donor's lung pool.
PMID- 10198543
TI - [The use of resources. Unnecessary stays in pediatric surgical services].
AB - BACKGROUND: There is wide-spread consensus that a part of the use of hospital
resources is inadequate in the sense that the patients receive services that do
not provide them with any significant benefits, or that could be more beneficial,
or less costly, with a lower care standard. OBJECTIVE: The main aim of this work
is to determine the percentage of inadequate stays in a pediatric surgery service
and to identify the causes that provoke them. METHOD: It was a concurrent study
in pediatric patients entered, at least 24 hours, by different disease for
surgery, observation or study. Revising trained applied the pediatric version of
the Appropriateness Evaluation Protocol on the medical records of these patients.
It has been measured if the stay was appropriated or not, and the cause. RESULTS:
The studied patients (279) caused a total of 1,001 stays of those which 373
(37.3%) were deemed to be unnecessary. The diseases with greater number of
inappropriate stays were cryptorchidia (97.3%), hernia (88.9%), hypertrophic
pyloric stenosis (50%), and soft tissues surgery (43.1%). A 68.2% of the
unnecessary stays were responsibility of the hospital-service-surgeon, a 22.6% to
the associated environment-familiar, and a 9.2% to the lack of alternative
resources to the hospital. CONCLUSIONS: A meaningful proportion by day of
hospital stay would be avoided. The unnecessary stays search facilitates the weak
points identification on those which to develop improvement actions.
PMID- 10198545
TI - [Prenatal diagnosis of ovarian cysts. The ultrasonographic course and therapeutic
importance].
AB - Before of the implantation of ultrasound there were few cases of ovarian cysts
reported in literature because only the very large ones or those which result in
mechanical complications produce symptoms. The authors report 17 cases of
neonatal ovarian cysts diagnosed by prenatal ultrasound. All of the infants were
asymptomatic after birth despite their size or being twisted. The diameter of the
cysts varied from 2.5 to 10 cm. Five neonates were treated conservatively and the
cysts resolved spontaneously. 12 infants underwent surgery following postnatal
confirmation, 9 of these patients had complex ovarian cysts and at laparotomy all
of them had torsion of the ovary, three of them were autoamputated, and 3
uncomplicated cysts because their large size or their association to a
nephroblastoma. Simple cysts of the ovary tend to resolve spontaneously and
therefore, must be treated conservatively. Complex cysts or simple ones larger
than 4 cm that do not disappear should undergo surgical removal.
PMID- 10198546
TI - [Complex anomalies of the anterior chest wall. Personalized surgical treatment].
AB - Among the congenital anomalies of the anterior chest wall, the group of the
asymmetrical deformities, mixed or complex, are the least frequent and the ones
that require a difference surgical strategy for each patient according to their
anatomical features. In this paper we present our experience and findings with
this type of malformation. The fundamental aspects of the surgical indications
and procedure are commented. The evolution and the results are very satisfactory.
We stress the positive reaction of the patients and their families after the
operation.
PMID- 10198547
TI - [Hemodynamic changes during laparoscopic surgery. Preliminary study].
AB - The haemodynamic changes produced by laparoscopic surgery in children have been
evaluated. A transesophageal echocardiographic study on 13 patients (7 males and
6 females, 10.8 +/- 2.7 years old) has been performed before, during and after
peritoneal CO2 gas insufflation. A change on the Doppler waves pattern of the
infradiaphragmatic veins along with an increase in blood flow velocity were
observed. Pulmonary veins suffered minimal changes showing an increase on either
the systolic pressure and on atrial contraction. Diastolic retrograde flow in
aorta reflected an increase in peripheral vascular resistance. Cardiac output
increased minimally. All haemodynamic changes returned to basal after gas
peritoneal desufflation. These data show that laparoscopic surgery could produce
important cardiac derangements in children with ventricular dysfunction or in
patients presenting left ventricular outlet obstruction. In these patients
laparoscopic surgery might be precluded.
PMID- 10198548
TI - [Esophageal dilatation by Savary-Guillard bougies in children].
AB - Dilatations are considered the election treatment for esophageal stenosis of
different etiologies. Different methods of dilatation have been used through the
years. Security and effectiveness are the main subjects when we choose a
dilatation method. We present the results of the last 3 years that Savary
Guilliard have been used, with a guide wire probe, under endoscopic control. Six
patients with postsurgical stenosis and 10 with post lye ingestion stenosis were
treated with the above mentioned method. The site of stenosis is localized under
flexible endoscopy, and a special guide wire probe is introduced to the stomach.
Once the wire is in place, different diameter bougies are introduced until a firm
resistance is felt or the desired diameter is reach. In complicated cases the
progression of the wire was controlled by X-rays. A total of 208 dilatations have
done in 16 patients over the last three years. Six patients with postsurgical
stenosis needed from two to six dilatations for their cure. Of the 10 patients
who ingest lye, none of them had needed a gastrostomy. Three of them have no
dysphagia after 9, 13 and 13 dilatations. The other 7 are under dilatations every
6 weeks in 6 cases and every 4 weeks in one case, been all of them in the second
year of treatment. All the dilatations have been performed under general
anesthesia, as outpatients. We have not had any complication under this
treatment. We have found that the Savary-Guilliard method is adequate for
esophageal dilatations in pediatric population. Security and effectiveness are
the main points of this procedure, there is no need for a gastrostomy, and the
child will have a better quality of life. This procedure is less aggressive, and
this will give a shorter postop period, with no complications and the child will
have a longer period of normal life between dilatations.
PMID- 10198549
TI - [Congenital absence of portal vein in a girl with biliary atresia treated with
liver transplant].
AB - The congenital absence of the portal vein is a rare malformation, which has been
generally discovered in association with another anomalies like a cardiac,
gastrointestinal or genitourinary defects. With portal hypertension and hepatic
cirrhosis, this anomaly is similar to spontaneous porto-systemic derivation, and
for that not collateral venous drainage is present. In these patients, total
interruption of mesentaric venous drainage during procurement of liver transplant
produce a very important bowel and mesenteric edema, which can promote an injert
fatal evolution. The authors present the first paediatric liver transplant, in a
patient with portal venous agenesia, with de piggy-back technique was done and
this complication was obviated, and a review of the literature about this issue
is done.
PMID- 10198551
TI - The supervisory alliance and the training of psychodynamic group
psychotherapists.
AB - This article focuses on the role of the supervisory relationship in the training
of psychodynamic group therapists. The supervisor's teaching responsibilities
include identifying what the novice leader needs to learn about running a group,
and designing and implementing supervisory strategies in a safe, collaborative,
and creative setting. Of particular importance to psychodynamic supervision is
the recognition of emerging impediments to learning and discerning their
significance for understanding the underlying dynamics of the supervisees'
treatment groups. Examples of two supervision groups are provided, one in which a
misalliance had developed, and another in which a more promising supervisory
relationship was forming.
PMID- 10198550
TI - [Laparoscopic transsection of Ladd's bands: a new indication for therapeutic
laparoscopy in neonates].
AB - Within the last ten years and by the introduction of some new instruments,
laparoscopy is a safe and effective method that has been further extended in
children. We report our experience in the treatment of laparoscopy on a seven day
old newborn affected by malrotation with an intermittent duodenal obstruction.
The treatment consisted of a duodenal liberation after the section was easily
performed in congenital Ladd's bands. The spiral twists of the small intestine
found in the upper gastrointestinal series, disappeared in a new study done after
surgery. We consider this operation as a new indication for an operative
laparoscopy. It allows a good visualization of this congenital abnormality, and
it is easy to perform with a significantly reduced operative trauma.
PMID- 10198552
TI - Group supervision and the psychoanalytic process.
AB - This article attempts to elucidate the psychodynamics of group supervision of
group psychotherapists. The significance of the supervisory setting is explored
with a particular emphasis on the frame. The regressive interactions in group
supervision are regarded as enactments, which are conceptualized as nonverbal
communications that are covertly transmitted. Enactments offer a link between the
present group (supervisory group) and the absent group (the therapy group that is
being supervised). The relationships between the experiential and didactic
components of group supervision are also addressed. Clinical vignettes illustrate
the interplay between the present and the absent group focusing on the
supervisor's interventions.
PMID- 10198553
TI - Group supervision of groups: a modern analytic perspective.
AB - This article is introduced by historical references to Freud's Wednesday Evening
Society and to relevant sources in the literature on group supervision. The aims
of group supervision are defined: helping supervisees to understand the
individuals who comprise their groups, helping the supervisee become a group
oriented therapist, alerting supervisees to the critical task of monitoring and
regulating the amount of emotional excitation within their groups, helping
supervisees deal with the range of feelings induced in them by their groups, and
helping them become familiar with the principles and become proficient in the
techniques of modern analysis. Major aspects of the group-supervisory process are
delineated and illustrated through the use of relevant vignettes. Resistance in
supervisory groups is discussed with examples of the resolution of some
resistances. The author's method and style of leading supervisory groups is
presented, as are observations on the boundaries of supervisory groups.
PMID- 10198554
TI - Systems-centered supervision.
AB - The systems-centered (SCT) approach to supervision frames the dynamics of both
groups and individuals as isomorphic systems. In this chapter, the SCT
supervisory experience, its goals, and its approach to transference and
countertransference are addressed; the orientation of the seven questions that
structure the SCT supervisory process are identified; and the thinking that is
required to answer them is discussed. SCT supervisees locate their supervision
issues in the context of the phases of system development; consider interventions
as hypotheses that can be tested in the therapeutic context; and provide feedback
to all parties about the validity of the theory of living human systems, the
reliability of its systems-centered practice, and the accuracy of the therapist's
hypotheses about the isomorphic dynamics of the systems of member, subgroup and
group as a whole. Illustrations are taken from tape recordings of supervisory
sessions.
PMID- 10198555
TI - An experiential group model for psychotherapy supervision.
AB - This article presents an experiential group model of supervision constructed for
both group and individual therapy presentations, emphasizing concepts from object
relations theory and group-as-a-whole dynamics. It focuses on intrapsychic,
interpersonal, and systems processes, and stresses the group aspect of the
supervisory process. Its central thesis is that material presented in a group
supervisory setting stimulates conscious and unconscious parallel processes in
group members. Through here-and-now responses, associations, and interactions
among the supervisory members, countertransference issues that have eluded the
presenter can make themselves known and be worked through on emotional as well as
cognitive levels. Selected excerpts from supervisory sessions demonstrate various
attributes and strengths of the model.
PMID- 10198556
TI - Group supervision meets technology: a model for computer-mediated group training
at a distance.
AB - Technological advances make the application of computer-mediated communication a
supervision tool for group psychotherapy training when students and faculty are
at a distance. A brief review of the literature on computer-mediated group
dynamics provides the context for training applications. A model group
supervision is described and clinical training examples are presented.
Recommendations and guidelines for using computer-mediated supervision are
proposed.
PMID- 10198557
TI - [Discrimination in science].
PMID- 10198558
TI - [Mycoplasma hominis and Ureaplasma urealyticum in different gynecologic
diseases].
AB - The incidence of Mycoplasma hominis (M. hominis) y Ureaplasma urealyticum (U.
urealyticum) was investigated in 113 endocervical samples obtained from women who
were seen for different gynecological pathologies. Forty-seven (42%) patients
were positive to these microorganisms; 26 cases (23%) were positive for M.
hominis and 21 (19%; p = NS) for U. urealyticum. Average age was 32.1 +/- 7.7
years; the average number of sexual partners was 1.7 +/- 1.1. Eleven of 17
patients with 3 o more sexual partners were positive for Genital Mycoplasma (GM),
and U. urealyticum was found more often in this group. A higher incidence of GM
was found in women between 26 and 30 years (34%); 57.5% of the patients with
positive cultures for GM had begun sexual activity before 20 years of age. M.
Hominis was found in 61% of women with no parity and U. urealyticum in 71% of
parous women. The cultures were positive in 10 of 14 patients with pelvic
inflammatory diseases (PID). A cervical biopsy was taken from 52 cases and the
diagnosis of cervical intraepithelial neoplasia (CIN) was made in 49 (94%) but
only 24 of them were positive for GM (50%). Thirty-five patients suffered
sterility, and 12 (34%) were positive for GM, however all positive cases
consulted because of primary sterility. The conclusions obtained from this study
are: 1) Near half of the patients was positive for GM and none of the species was
predominant over the other. 2) The more sexual partners the higher was the
incidence of GM, especially U. Urealyticum. 3) The lower the age of the first
sexual intercourse the higher the probability of contamination with these
microorganisms. 4) M. hominis was more common in nulliparous women and U.
urealyticum was found more often in parous patients; the number of deliveries did
not have influence in these findings. 5) A statistical significance between GM
and PID was found (p = 0.03). 6) GM have no influence on spontaneous abortion. 7)
No statistical significance was found between GM and the beginning and evolution
of CIN. 8) No relation statistically significative was found between GM and
sterility.
PMID- 10198559
TI - [Isolation, identification and serotyping of yeasts obtained from the vaginal
fluid in patients with clinical vaginitis].
AB - A study was carried out to determine the presence of Candida in 105 patients with
clinical vaginitis who consulted in the Infectious Disease Unit of the Vargas
Hospital after referral from Gynecology Service. Yeasts were detected in 23 cases
(24%), and identified as C. albicans (12), C. tropicalis (5), C. guilliermondii
(3), C. glabrata (2) and C. parapsilosis (1). The presence of hyphae was observed
in 50% of the direct examinations, in which the isolated species was C. albicans.
These structures were not observed in infections with other species of Candida.
In this study, there was relatively little difference between the percentages of
serotypes A and B, 58 % and 42, respectively. This is in contrast with previous
studies reported in clinical material from Venezuela and other countries, in
which serotype A presented a greater incidence than serotype B. Our observations
suggest an increase in serotype B C. albicans in vaginal candidiasis.
PMID- 10198560
TI - [Tracking of body height, body weight, body mass index, blood lipids and glucose
in upper strata girls in Caracas, Venezuela].
AB - In the Caracas Longitudinal Study, the canalization of 24 girls that started
follow-up at age 4, 43 at age 8, and 32 at age 12 in: height (H), weight (W),
Body Mass Index (BMI), cholesterol (CHOL), triglycerides (TG) and glucose (GL),
was studied using Schneiderman n Tracking Index (TI) and age to age correlations.
TI presented a gradient H > W > BMI > CHOL and lower in TG and GL. TI of all
variables diminished increased with age and in BMI and CHOL. Age to age
correlations were significant at all ages in H, W. and BMI and higher in CHOL (p
< 0.01) compared to TG and GL. The significant tracking of H, W, BMI and lipids,
specially CHOL, is relevant in prevention of non-communicable chronic diseases.
PMID- 10198561
TI - [Gender differences and diabetic status in the relationship of blood
apolipoprotein C-III, free fatty acids and triglycerides in subjects at risk for
glucose intolerance].
AB - Insulin resistance and hyperinsulinemia can induce overproduction of triglyceride
(TG) rich VLDL in the liver by increasing the availability of free fatty acids
(FFA). Conversely, apolipoprotein C-III (apoC-III) is an inhibitor of the
catabolism of TG-rich lipoproteins. To explore the relationship among FFA, apo C
III and TG in hyperinsulinemic subjects, we studied 103 individuals (63 women and
40 men) with a body mass index (BMI) 25 Kg/m2: 59 subjects with normal glucose
tolerance (NGT), and 44 with newly diagnosed type 2 diabetes. After adjustment
for age, BMI, fasting insulin and TG, FFA were significantly higher in women than
in men and in subjects with diabetes compared with NGT. Subjects with diabetes
had higher apo C-III levels compared to NGT, adjusted for age, sex and BMI, and
that was largely accounted for by differences in insulin and TG levels. In
addition, regression analysis in subjects with diabetes showed that TG were
strongly associated with apo C-III in both men and women (r = 0.90 and 0.79,
respectively; p < 0.001), while the association tended to be smaller between TG
and FFA (r = 0.48, p < 0.05 in men and r = 0.45, p = 0.06 in women). Conversely,
in individuals with NGT fasting TG was strongly associated with apo C-III in men
(r = 0.83, p < 0.01) but not with FFA, while in women TG was associated with FFA
(r = 0.39, p < 0.05) but not with apo C-III. In summary, elevated apo C-III was a
predominant factor associated with elevated TG levels in NGT men and all subjects
with type 2 diabetes, while FFA were more closely related with TG levels in NGT
women.
PMID- 10198562
TI - [Continuous splenic-gonadal fusion: a case report].
AB - Splenic-gonadal fusion is an extremely rare congenital anomaly that results from
fusion between the splenic and gonadal anlage during embryonic development.
Approximate 90 cases have been reported in the literature. The condition has been
divided into two major groups: continuous splenic-gonadal fusion in which a
continuous cord-like structure connects the spleen and the gonadal-mesonephric
structure, and dis-continuous splenic-gonadal fusion in which no such connection
exists. We report a case of continuous splenic-gonadal fusion in a 2 1/2 years
old boy presenting a left inguinal mass and a right inguinal hernia. They were
removed without complications.
PMID- 10198564
TI - The JIM interview. Daniel Porte, Jr, MD.
PMID- 10198563
TI - Med schools and teaching hospitals tackle "Y2K" problem.
PMID- 10198565
TI - The sexual revolution in science: what gender-based research is telling us.
PMID- 10198567
TI - Platelet-erythrocyte adhesion in sickle cell disease.
AB - BACKGROUND: The abnormal adherence of sickle red blood cells (sRBC) to other cell
types likely contributes to vaso-occlusion. Increased numbers of platelet
erythrocyte aggregates (PEA) and platelet activation have been described in
sickle cell disease. The present study was undertaken to determine the
contribution, if any, of the extracellular matrix protein thrombospondin to the
adhesion of sRBC and platelets. METHODS: Platelet activation and PEA were
measured using fluorescent-labeled monoclonal antibodies and flow cytometry.
Platelet red-cell adhesion was measured by a gravity sedimentation assay.
Erythrocyte-bound thrombospondin (TSP) was determined by enzyme-linked
immunoabsorbant assay (ELISA). RESULTS: Our studies demonstrate significant
platelet activation and adhesion of sRBC to platelets in sickle cell disease.
Thrombospondin was detected on sRBC. There was variable inhibition of sRBC
platelet adhesion by antibodies to CD36 (thrombospondin receptor) and antibodies
to thrombospondin. CONCLUSIONS: Thrombospondin on sRBC may mediate, at least in
part, sRBC-platelet adhesion in sickle cell disease. The study of heterotypic
cell-cell interactions is important in understanding the pathogenesis of vaso
occlusion in sickle cell disease.
PMID- 10198566
TI - Circulating factor in patients with recurrent focal segmental glomerulosclerosis
postrenal transplantation inhibits expression of inducible nitric oxide synthase
and nitric oxide production by cultured rat mesangial cells.
AB - BACKGROUND: Primary focal segmental glomerulosclerosis (FSGS) recurs in nearly
30% of patients who progress to end-stage renal disease and then receive a kidney
transplant. A circulating plasma factor has been isolated from these patients
that increases glomerular permeability to albumin in vitro. Because of the
pivotal role of the mesangial cell in the accumulation of extracellular matrix
(ECM) material within the glomerulus and the modulation of matrix protein
synthesis by nitric oxide (NO), we examined the effect of the FSGS factor on
inducible nitric oxide synthase (iNOS) expression and NO production by cultured
rat mesangial cells (RMC). METHODS: RMC were incubated with the supernatant
following 70% ammonium sulfate precipitation of serum from patients with
recurrent FSGS. RESULTS: Addition of the FSGS factor to cultured RMC led to a
significant inhibition of nitrite accumulation, an index of NO synthesis. There
was a parallel decline in iNOS gene and protein expression. Sera obtained from
control patients or those with minimal change nephrotic syndrome or diabetic
nephropathy that was processed in the same manner as FSGS samples had no effect
NO synthesis or iNOS activity. The inhibitory effect of the FSGS factor on NO
production persisted despite addition of indomethacin (0.1-1 mumol/L) or
cyclosporine (25 micrograms/mL) to test media. CONCLUSIONS: These data indicate
that the FSGS factor independently alters two aspects of glomerular function-
permselectivity and matrix protein synthesis--by distinct mechanisms. FSGS factor
induced disturbances in iNOS gene and protein expression and NO production by
mesangial cells may antagonize the antifibrotic effect of NO within the mesangium
and contribute to progressive glomerulosclerosis in patients with primary FSGS.
PMID- 10198568
TI - Immunochemical localization of platelet-derived growth factor in placenta and its
possible role in pre-eclampsia.
AB - BACKGROUND: Platelet-derived growth factor (PDGF) has an important role in
cellular function, proliferation, and angiogenesis. It is also associated with
tissue injury and repair, and its involvement in atherosclerosis has been studied
extensively. Tissue injury is also found in pre-eclampsia (PRE). The
morphological and physiological changes that are taking place in the PRE placenta
may be associated with this growth factor. The objective of this study was to
determine if PDGF-AA and its alpha receptor are present in the cells and vessels
of normotensive (NORM) and PRE placentas at term. METHODS: Placental tissue was
obtained from 6 preeclamptic and 8 normotensive women. Gestational age ranged
from 38-42 weeks. Deliveries were either vaginal (vag, n = 10) or c-section (c
sec, n = 4). Tissue samples were analyzed for PDGF-AA by immunocytochemistry.
RESULTS: PDGF-AA and the alpha receptor were present in both NORM and PRE
placentas. Immunoreactive staining revealed PDGF-AA and its receptor in the
intimal/endothelial layer of fetal vessels and the trophoblastic layer. Staining
intensity was greater in preeclamptic tissue when obliterative endarteritis was
present. CONCLUSIONS: In pre-eclampsia, PDGF-AA may play a role in the
restructuring of the fetoplacental vasculature, in particular when there is
inflammation of the vascular intimal layer, as found in obliterative
endarteritis. Increased staining in the trophoblast layer in patients with
obliterative endarteritis also may be indicative of more widespread damage
throughout the placenta itself, and PDGF-AA may play a significant role in the
repair of this damage.
PMID- 10198569
TI - Management of patients with acute myocardial infarction at five academic medical
centers: clinical characteristics, resource utilization, and outcome.
AB - BACKGROUND: Although variability in management of cardiovascular syndromes has
been demonstrated among regions, the extent to which variability exists among
academic medical centers in different countries in uncertain. METHODS: This
retrospective cohort study includes data on consecutive patients (n = 694) with
acute myocardial infarction who were admitted to five teaching hospitals from
different countries (84, Brigham and Women's Hospital, USA; 97, Iizuka Hospital,
Japan; 64, Hospital de Clinicas de Porto Alegre, Brazil; 62, Universitatsklinikum
Charite, Germany; and 387, Hopital Cantonal Universitaire de Geneve, Switzerland)
during a one-year period. Data were collected via chart review on clinical
characteristics, rates of diagnostic and therapeutic interventions, complications
and mortality, length of stay, and one-year follow-up outcomes. RESULTS:
Patients' clinical characteristics varied among these institutions, with the
lowest prevalence of antero-septal myocardial infarction at the US hospital. The
US hospital had the lowest rate of use of thrombolytic therapy and did not have
the highest rate for any invasive procedure. Average length of stay ranged from
7.7 +/- 4.3 days in the US hospital to 47.2 +/- 27.9 days in the Japanese
hospital. There were no differences in one-year mortality among the four
institutions (4% to 8%, P = 0.881) for which data were available. CONCLUSIONS: In
this nonrandom sample of academic medical centers, the use of aggressive
therapies for acute myocardial infarction was at least as common at non-US as US
hospitals. Length of stay was much shorter at the US hospital. Despite these
variations in management, evidence for differences in outcomes at one year were
not detected.
PMID- 10198570
TI - Relationship of endogenous circadian melatonin and temperature rhythms to self
reported preference for morning or evening activity in young and older people.
AB - BACKGROUND: Morningness-eveningness refers to interindividual differences in
preferred timing of behavior (i.e., bed and wake times). Older people have
earlier wake times and rate themselves as more morning-like than young adults. It
has been reported that the phase of circadian rhythms is earlier in morning-types
than in evening types, and that older people have earlier phases than young
adults. These changes in phase have been considered to be the chronobiological
basis of differences in preferred bed and wake times and age-related changes
therein. Whether such differences in phase are associated with changes in the
phase relationship between endogenous circadian rhythms and the sleep-wake cycle
has not been investigated previously. METHODS: We investigated the association
between circadian phase, the phase relationship between the sleep-wake cycle and
circadian rhythms, and morningness-eveningness, and their interaction with aging.
In this circadian rhythm study, 68 young and 40 older subjects participated.
RESULTS: Among the young subjects, the phase of the melatonin and core
temperature rhythms occurred earlier in morning than in evening types and the
interval between circadian phase and usual wake time was longer in morning types.
Thus, while evening types woke at a later clock hour than morning types, morning
types actually woke at a later circadian phase. Comparing young and older morning
types we found that older morning types had an earlier circadian phase and a
shorter phase-wake time interval. The shorter phase-waketime interval in older
"morning types" is opposite to the change associated with morningness in young
people, and is more similar to young evening types. CONCLUSIONS: These findings
demonstrate an association between circadian phase, the relationship between the
sleep-wake cycle and circadian phase, and morningness-eveningness in young
adults. Furthermore, they demonstrate that age-related changes in phase angle
cannot be attributed fully to an age-related shift toward morningness. These
findings have important implications for understanding individual preferences in
sleep-wake timing and age-related changes in the timing of sleep.
PMID- 10198572
TI - [Abstracts of the 104th annual meeting of the Japanese Association of Anatomists.
Tokyo, Japan. March 29-31, 1999].
PMID- 10198573
TI - [The 39th annual meeting of the Japanese Respiratory Society. Yokohama, Japan.
March 25-27, 1999. Abstracts].
PMID- 10198571
TI - Gamma-glutamyl transpeptidase-dependent iron reduction and LDL oxidation--a
potential mechanism in atherosclerosis.
AB - BACKGROUND: gamma-Glutamyl transpeptidase (gamma-GT) is found in serum and in the
plasma membranes of virtually all cell types. Its physiologic role is to initiate
the hydrolysis of extracellular glutathione (GSH), a tripeptide in which cysteine
lies between alpha-glycine and gamma-glutamate residues. Cysteine and other thiol
compounds are known to promote LDL oxidation by reducing Fe(III) to redox active
Fe(II); therefore, we sought to determine whether similar reactions can be
sustained by GSH and influenced by gamma-GT. METHODS: Fe(III) reduction and LDL
oxidation were studied by monitoring the formation bathophenanthroline-chelatable
Fe(II) and the accumulation of thiobarbituric acid-reactive substances,
respectively. Human atheromatous tissues were examined by histochemical
techniques for the presence of oxidized LDL and their colocalization with cells
expressing gamma-GT activity. RESULTS: A series of experiments showed that the
gamma-glutamate residue of GSH affected interactions of the juxtaposed cysteine
thiol with iron, precluding Fe(III) reduction and hence LDL oxidation. Both
processes increased remarkably after addition of purified gamma-GT, which acts by
removing the gamma-glutamate residue. GSH-dependent LDL oxidation was similarly
promoted by gamma-GT associated with the plasma membrane of human monoblastoid
cells, and this process required iron traces that can be found in advanced or
late stage atheromas. Collectively, these findings suggested a possible role for
gamma-GT in the cellular processes of LDL oxidation and atherogenesis.
Histochemical analyses confirmed that this may be the case, showing that gamma-GT
activity is expressed by macrophage-derived foam cells within human atheromas,
and that these cells colocalize with oxidized LDL. CONCLUSIONS: Biochemical and
histochemical correlates indicate that gamma-GT can promote LDL oxidation by
hydrolyzing GSH into more potent iron reductants. These findings may provide
mechanistic clues to the epidemiologic evidence for a possible correlation
between persistent elevation of gamma-GT and the risk of fatal reinfarction in
patients with ischemic heart disease.
PMID- 10198574
TI - [Universal trends in medical care and key points in comprehensive care].
PMID- 10198575
TI - [Future health care legislation, hospital management, and clinical tests].
PMID- 10198576
TI - [Disaster medicine and laboratory tests].
PMID- 10198577
TI - [Good laboratory management (GLM)--search of GLM by a manager].
PMID- 10198578
TI - [Future expectation on laboratory technologists].
PMID- 10198579
TI - [The system for standardization of clinical chemistry and the word-wide trend].
PMID- 10198580
TI - [Standard chemicals and their use--various materials and enzymes].
PMID- 10198581
TI - [Reference materials and their use--proteins].
PMID- 10198582
TI - [Concept of quality assurance and its practice].
PMID- 10198583
TI - [Laboratory diagnosis as part of the clinical support system].
PMID- 10198584
TI - [Data interpretation for clinical support].
PMID- 10198585
TI - [From a diagnostic test to discovery of a new syndrome].
PMID- 10198586
TI - [Concepts and research methodology in clinical chemistry].
PMID- 10198587
TI - [Chemical analysis of clinical materials using mass spectrometry].
PMID- 10198588
TI - [Theories and problems related to direct determination of lipoprotein
cholesterol].
PMID- 10198589
TI - [Analysis of abnormal enzyme activities--with special reference to LD].
PMID- 10198590
TI - [Carcinogenesis and genetic diagnosis].
PMID- 10198591
TI - [Genetic diagnosis of viral hepatitis].
PMID- 10198592
TI - [Analysis of hereditary enzyme abnormalities].
PMID- 10198593
TI - [Molecular biology that is useful in genetic engineering].
PMID- 10198594
TI - [Genetic tests and items to be noted at the diagnostic laboratory].
PMID- 10198595
TI - [Separation and analysis of saccharides--on mainly oligosaccharides].
AB - Characteristics of three kinds of columns used for the separation and analyses of
saccharides by HPLC, and of a pulsed amperometric detector (PAD) as a high
sensitive detector for the microanalysis of saccharides were described. The
following several examples of studies on the separation and analyses of
saccharides were illustrated: (1) separation of maltosaccharides on an amino
column, (2) isolation of each maltooligomer of DP6-17 on an ODS column, (3)
retention behavior of alpha-cyclodextrin (alpha CD) and branched alpha CDs on an
ODS column, (4) separation of three positional isomers of dimaltosyl-beta CD on
an ODS column and a graphitized carbon (GC) column, (5) separation of
diastereoisomers of glucosyl-inositol on a GC column, (6) chromatographic
behavior of nine glucobioses on a GC column, (7) estimation of the distributions
of chain length of amylopectins with the pulsed amperometric detection, (8)
microanalysis of beta CD and glucosyl-beta CD in biological matrices by HPLC with
PAD. In addition, methods for the structural analyses of branched CDs by FAB-MS,
13C-NMR and enzymatic degradation were expressed.
PMID- 10198596
TI - [Dispersal of pollen and the variation in number of patients prescribed medicine
for allergies in Otaru].
AB - The number of patients prescribed medicine for allergies increased in May and
September. Therefore, we suspected that the cause for the increase was pollen.
Many kinds of pollen occur in Otaru, such as alder in April, Japanese black pine,
white birch, acacia, larch in May, oak in June, and mugwort in September. The
total number of pollen count of white birch was about 9 times that of mugwort,
but the total number of patients prescribed Celestamine in the season of white
birch pollen was about 0.8 times that of mugwort pollen. These results seen in
Otaru differed from those in neighboring Sapporo. The coefficient of the
correlation of the number of mugwort and white birch pollen and those of patients
prescribed Celestamine were r = 0.304 and r = 0.766, respectively. We believe
that making available information on pollen is very useful to improve the quality
of life of patients.
PMID- 10198597
TI - [Decreased plasma levels of omeprazole after coadministration with magnesium
aluminium hydroxide dry suspension granules].
AB - Plasma levels of omeprazole (OPZ) in Japanese male subjects were compared after a
single oral administration of 20 mg of OPZ enteric-coated tablets with and
without coadministration of Maalox (MLX suspension) or Maalox dry suspension
granules (MLX granules). After coadministration of MLX granules, plasma levels of
OPZ markedly decreased, and area under the blood concentration-time curve (AUC)
decreased to 26% of that of OPZ alone. In contrast, only a slight decrease in AUC
was observed after coadministration of OPZ and MLX suspension. Both MLX
suspension and MLX granules exhibited similar degrees of the inhibitory effect on
the renal excretion of levofloxacin. It was suggested that a specific and
unexpected drug interaction occurred between OPZ enteric-coated tablets and MLX
granules via a distinct mechanism from that reported for fluoroquinolones and MLX
suspension.
PMID- 10198598
TI - [Effects of the rational use of corticosteroids eye drops for the prevention of
ocular toxicity in high-dose cytosine arabinoside therapy].
AB - Although the use of corticosteroid (CS) eye drops of the use of eye washing by
artificial tears was effective for the prevention of ocular toxicity such as
keratitis and photophobia in the high-dose cytosine arabinoside (Ara-C) therapy,
the toxicity was not prevented perfectly. We studied the effects of the rational
use of CS eye drops, and the combined use of CS eye drops and eye washing by
physiological saline in order to prevent the ocular toxicity. Before the study,
the instillation of 0.1% sodium bethamethazone phosphate (BM) eye drops was
carried out at 4-6 times per day during the high-dose Ara-C therapy, and
continued for several days after the high-dose Ara-C therapy. However, the
rational use of "eyelid closure" and "naso-lacrimal occlusion" after the
instillation was not performed Consequently, the ocular toxicity was observed in
3 (19%) of 16 cases of the patients. When the instillation of BM eye drops at 4
times per day was carried out rationally according to the consultation of
pharmacist during the high-dose Ara-C therapy and for additional 10 days after
the therapy, no ocular toxicity was observed in all cases (0 of 6 cases).
Furthermore, the combined use of eye washing by physiological saline and
instillation of BM eye drops was effective for the decrease of the risk of ocular
toxicity, because no ocular toxicity was observed in the high-dose Ara-C therapy
(0 of 34 cases). Our procedure in this study would be effective for the
prevention of ocular toxicity in the high-dose Ara-C therapy.
PMID- 10198599
TI - Early rehabilitation program in postmastectomy patients: a prospective clinical
trial.
AB - The purpose of this study was to determine whether 20 patients who received an
early postmastectomy rehabilitation treatment program showed more improvement in
range of shoulder motion and functional activities than 13 patients who received
instruction for exercise only. Data were obtained at preoperatively, three days
after operation, at discharge and at postdischarge one month for each patient on
parameters such as range of motion of the ipsilateral shoulder joint, upper
extremity circumferential measurements, as well as 10 elements of shoulder
function. Postoperatively, both groups showed an increased range of motion of the
shoulder joint and improved functional activities, but the group that received
postoperative rehabilitation management had a better range of shoulder motion and
less difficulty in five items for functional assessment. This study also showed
that an early rehabilitation program did not increase postoperative
complications. We concluded that an early rehabilitation program or intensive
instruction program only by a well-trained physical therapist or physiatrist was
beneficial to postmastectomy patients in regaining the function and range of
shoulder motion, and significantly better in a rehabilitation group.
PMID- 10198600
TI - AIDS-related perceptions and condom use of prostitutes in Korea.
AB - The purpose of this study was to assess the impact of AIDS-related knowledge and
attitudes of prostitutes on condom use from diverse 'sex markers' in Korea. The
data were collected by interviewers at five different 'sex markets'. During March
1993, research assistants at the Institute of Health Services Research
interviewed 371 prostitutes visiting sexually transmitted disease (STD) clinics.
Multiple regression method was used in identifying the determinants of condom
use. The level of condom use was regressed on personal characteristics of
prostitutes, AIDS-related perceptions, and market type. Prostitutes' level of
condom use turned out to be different across the markets featuring diverse types
of services and fees. Neither perceived vulnerability nor perceived seriousness
of AIDS had significant effects on condom use. Our findings suggested that the
many AIDS-preventive educational efforts by STD clinics are ineffective. Hence,
individual STD clinics need to develop AIDS-preventive education programs which
are suitable for the unique circumstances of their respective 'sex markets'.
PMID- 10198601
TI - The comparison of histologic gastritis in patients with duodenal ulcer, chronic
gastritis, gastric ulcer and gastric cancer.
AB - This study was designed to investigate the differences of histologic gastritis
according to the endoscopic diagnosis, and between H. pylori positive and
negative gastritis, using the Sydney system. A total of 122 patients (42 duodenal
ulcer, 31 chronic gastritis, 35 gastric ulcer and 14 gastric cancer) underwent
endoscopy with biopsies from the antrum and body. Among the 122 patients, 104
(85%) were H. pylori positive. H. pylori density of the antrum was significantly
higher in duodenal ulcer than in chronic gastritis, gastric ulcer, and gastric
cancer. The positivity of intestinal metaplasia was lowest in duodenal ulcer and
highest in gastric cancer. H. pylori density as well as grade of activity,
inflammation and atrophy were significantly higher in the antrum than in the body
in duodenal ulcer, while in chronic gastritis, gastric ulcer and gastric cancer
there was no difference of H. pylori density, activity, inflammation and atrophy
between the antrum and body. The grade of activity and chronic inflammation were
significantly higher in H. pylori positive patients than in H. pylori negative
patients in both the antrum and body. In conclusion, the gastritis of duodenal
ulcer was mainly localized to the antrum, while the gastritis of chronic
gastritis, gastric ulcer or gastric cancer was rather uniform in the antrum and
body. H. pylori seemed to be related to the development of chronic inflammation
and activity.
PMID- 10198602
TI - Monophosphoryl lipid A (MPL) upregulates major histocompatibility complex (MHC)
class I expression by increasing interferon-gamma (IFN-gamma).
AB - Tumor immunity is primarily mediated by cells as CD8+ cytotoxic T lymphocytes
(CTL) recognize tumor antigen by MHC class I molecules. But most tumors are
associated with a decreased expression of MHC class I to escape the antitumor
immunity of the host. Our previous data have demonstrated that MPL has an
antitumor effect on metastatic lung cancer of B16 melanoma with enhancing
cytotoxicity due to increase of IFN-gamma and IL-2, and decrease of IL-4, which
indicates the stimulation of type 1 helper T cells (Th1). To determine the
effects of MPL, IFN-gamma, TNF-alpha, and IL-1 alpha on MHC class I expression of
B16 melanoma cells, we evaluated the expression of MHC class I molecules with
treatments of MPL, IFN-gamma, TNF-alpha, and IL-1 alpha by flow cytometry. The
supernatant of MPL-treated spleen cells in vitro upregulated the expression of
MHC class I molecules of B16 melanoma cells compared to the control supernatant
of spleen cells. The MHC class I expression of B16 melanoma cells treated with
IFN-gamma, but not TNF-alpha or IL-1 alpha, increased in a time-dependent manner.
In conclusion, MPL upregulated MHC class I expression of B16 melanoma cells by
activating spleen cells via IFN-gamma. These data suggest that increased IFN
gamma by MPL is responsible for the upregulation of MHC class I expression to
augment cytotoxicity. Therefore, we suggest that MPL could play an important role
in immunotherapy.
PMID- 10198603
TI - Ideal concentration of growth factors in rabbit's flexor tendon culture.
AB - Growth factors have the ability to stimulate matrix synthesis and cell
proliferation in rabbit flexor tendon. Maximal stimulation effects of growth
factors have a wide variation. It depends upon the different anatomic sites of
the tendon segment, the kinds of growth factor, the concentration of growth
factors, and the time sequence. Since proliferation was an early component of
intrinsic tendon healing, we investigated the short-term dose response to four
different growth factors on in vitro rabbit's tendon culture. We evaluated the
effects according to the various concentrations of recombinant human insulin-like
growth factor 1 (IGF), recombinant human epidermal growth factor (EGF),
fibroblast growth factor (FGF), and recombinant human platelet-derived growth
factor-BB (PDGF). Fetal calf serum was the most potent stimulator of cell
proliferation and protein synthesis in in vitro rabbit's tendon culture. Matrix
synthesis and cell proliferation were stimulated dose-dependently by IGF between
the doses of 50 and 150 ng/ml. The maximum mitogenic effect of EGF was observed
at the concentration of 100 ng/ml (1.3 times more than the media-only control
culture). The rabbit's tendon responded significantly dose-dependently to PDGF,
whereas there was no significant response to FGF.
PMID- 10198604
TI - Molecular analysis of HLA-DR gene expression induced by IFN-gamma in malignant
melanoma cell lines.
AB - Human leukocyte antigen (HLA) class II molecules are polymorphic cell surface
glycoproteins that are crucial for the cellular interaction in immune response.
The expression of class II molecules is regulated in a tissue-specific and
cytokine-inducible manner, and is mainly restricted to the antigen presenting
cells. However, some tumor cells also express class II molecules, and in some
class-II-negative tumor cells, class II expression is inducible by interferon
(IFN)-gamma. However, their expression varies, even though the tumor cells
originate from the same histological origin; some tumor cells show strong
expression, others show weak or no expression. To determine whether this
differential expression of class II molecules on tumor cells is transcriptionally
regulated, FACS analysis and Northern hybridization were performed using a panel
of melanoma cell lines, IGR3, Malme-3M, SK-Mel-24, and SK-Mel-28 to analyze the
cell surface expression and mRNA transcription rate of HLA-DR before and after
treatment with IFN-gamma. FACS analysis showed that before IFN-gamma treatment,
IGR3 and Malme-3M cells barely expressed HLA-DR. On the contrary, almost all of
the SK-Mel-24 cells (> 90%) and a relatively high rate (> 50%) of SK-Mel-28 cells
expressed HLA-DR. After IFN-gamma treatment, HLA-DR expression was induced in
Malme-3M cells and SK-Mel-28 cells which displayed elevated levels of HLA-DR
expression in a time-dependent manner. However, IGR3 cells never responded to IFN
gamma. Northern analysis showed that treatment with IFN-gamma led to the steady
state mRNA augmentation of the HLA-DR gene in Malme-3M and SK-Mel-28, whereas in
IGR3, IFN-gamma did not augment the transcriptional rate of the HLA-DR gene. To
further clarify this differential modulation, sequencing analysis of PCR product
of the HLA-DR proximal promoter region was done, since the transcription rate of
the class II gene is controlled by the well-conserved proximal promoter region.
Six independent clones from PCR products of the HLA-DRA proximal promoter region
and 16 clones from PCR products of the HLA-DRB proximal promoter region were
isolated from the above cell lines and sequenced. Comparison of the nucleotide
sequences of all 6 clones of DRA promoter showed that the sequences are extremely
similar in both regulatory sequences and their intervening sequences. Sixteen
clones of HLA-DRB promoter showed sequence variations such as substitution and
insertion/deletion, and these 16 clones could be further grouped into 6
homologues with sequence homology. These data established that the melanoma cell
lines studied here showed a differential susceptibility to IFN-gamma on the
modulation of HLA-DR molecules, that this modulation is transcriptionally
regulated, and that the difference in promoter activity by sequence variation
might contribute to such a differential transcriptional regulation at the
promoter level.
PMID- 10198605
TI - The validity of random urine specimen albumin measurement as a screening test for
diabetic nephropathy.
AB - To assess the validity of urine albumin concentration (UAC) and the urine
albumin:creatine ratio (UACR) in a random urine specimen (RUS) for screening
diabetic nephropathy in Korea, a total of 105 ambulatory diabetes mellitus
patients (male:female, 52:53), ages 40-75 years (median 59 years) collected 105
RUSs after completing a timed 24 hour urine collection. Albumin was measured by
immunonephelometry. According to the timed urinary albumin excretion rate (UAER)
measured in the 24 hour collection (criterion standard), samples were classified
normoalbuminuric (UAER < 20 micrograms/min; n = 50), microalbuminuric (UAER 20
200 micrograms/min; n = 30), and macroalbuminuric (UAER > 200 micrograms/min; n =
25). The receiver operating characteristics (ROC) curve of UAC and UACR in a RUS
for screening of microalbuminuria (normo- and microalbuminuric samples; n = 80)
and macroalbuminuria (micro- and macroalbuminuric samples; n = 55) were plotted.
Pearson's coefficients of correlation of 24 hour UAER vs. UAC and UACR were 0.81
and 0.75, respectively (P < 0.001). The point of intersection with a 100%-to-100%
diagonal for microalbuminuria were as follows: 31.0 mg/l for UAC and 32.5 mg/g
for UACR; for macroalbuminuria 181 mg/l for UAC and 287.3 mg/g for UACR. The
sensitivity and specificity of the cut-off points for microalbuminuria were 77%
and 82% for UAC and 77% and 92% for UACR. The sensitivity and specificity of the
cut-off points for macroalbuminuria were 84% and 90% for UAC and 88% and 90% for
UACR. In present study, no difference was observed when comparing the performance
of UAC and UACR based on a statistical comparison by McNemar test. The repeated
measurements of UAC and UACR in the same individual were statistically similar
and were correlated with each other. Based on these results, albumin measurements
(UAC and UACR) in a RUS were considered as a valid test for screening diabetic
nephropathy.
PMID- 10198606
TI - Comparison of methods of point estimation in occupational epidemiologic studies.
AB - Two common study designs of occupational epidemiologic studies are cohort
mortality studies, which use the population at risk as a denominator, and
proportionate mortality studies, which use the total number of events as a
denominator. This study compared the various methods of point estimation for
cohort mortality studies, i.e., RR (risk ratio), OR (odds ratio) and SMR
(standardized mortality ratio), and those for proportionate mortality studies,
i.e., PRR (proportionate risk ratio), POR (proportionate odds ratio) and PMR
(proportionate mortality ratio). This study was based on a real dataset of all
workers in Metropolitan Toronto, Canada, who applied for compensation for various
types of injuries or diseases from the Workers' Compensation Board in 1980.
Results showed that within the cohort mortality or proportionate mortality study
designs, OR (or POR) in all cases gave the least conservative estimates (farthest
away from the null value), while SMR (or PMR) gave the most conservative
estimates. The empirical differences between the point estimators were generally
small. Our results showed that between study designs the corresponding point
estimators were poorly correlated. In addition, this empirical study indicated
that the use of the mortality odds ratio did not improve the proportionate
mortality study very much in terms of generating results similar to the risk
ratio from the cohort mortality design. We drew two conclusions: first, the point
estimators within each study design can generally be a good alternative to one
another; and second, proportionate mortality studies are not a good approximation
for cohort mortality studies.
PMID- 10198607
TI - Diagnosis of trichomoniasis by polymerase chain reaction.
AB - The clinical usefulness of polymerase chain reaction (PCR) for the diagnosis of
trichomoniasis was evaluated in comparison with other conventional tests. PCR was
used for specific detection of Trichomonas vaginalis by primers based on the
repetitive sequence cloned from T. vaginalis (TV-E650). Between June 1996 and
August 1997, 426 patients visited the department of obstetrics and gynecology,
Hanyang University Kuri Hospital and were examined for trichomoniasis using wet
mount examination, Papanicolaou (Pap) smear, culture and PCR. One hundred and
seventy-seven patients (group A) visited with the symptoms of vaginal discharge
and 249 patients (group B) visited for regular cervical Pap smear with no vaginal
symptoms. From group A (n = 177), 3 infections (2.0%) were detected by wet mount,
6 infections (3.3%) by Pap smear and culture, and 17 infections (10.4%) by PCR.
From group B (n = 249), 4 patients (1.6%) were found to have T. vaginalis by
culture and 6 infections (2.4%) were detected by PCR. Therefore, in both groups,
PCR for T. vaginalis showed a higher detection rate compared with conventional
wet mount, Pap smear or culture. The detection by PCR was specific for T.
vaginalis since no amplification was detected with DNAs from other protozoa and
Candida albicans. The sensitivity and specificity of PCR were 100%. This method
could detect T. vaginalis in vaginal discharge at a concentration as low as 1
cell per PCR mixture. These results indicate that PCR could be used as a specific
and sensitive diagnostic tool for human trichomoniasis.
PMID- 10198608
TI - Prokaryotic expression and characterization of human AP DNA endonuclease.
AB - The expression of major human apurinic/apyrimidinic DNA endonuclease (APEX) from
its cDNA in E. coli (DH5 alpha) was attempted in order to obtain a biologically
active recombinant APEX. E. coli cells were transformed by a prokaryotic
translation vector (pGEX-4T-3) harboring APEX cDNA. GST-APEX fusion protein with
a molecular weight of 6.3 KDa was induced by IPTG (1.0 mM) treatment. Western
blot immunodetection identified the induced protein as the GST-APEX fusion
protein. The survival rate of E. coli cells (DH5 alpha) transformed with pGEX-4T
3-APEX increased when the cells were treated with N-diethyl-N-nitrosamine (DENA)
or 3'-methyl-4-monomethylaminoazobenzene (3'-MeMAB), indicating that APEX
expression had a protective effect on the cytotoxicity of these carcinogens. The
fusion protein extracted from E. coli cells and purified by GSH-agarose gel
affinity chromatography exhibited APEX activity. Treatment of thrombin to the GST
APEX fusion protein and affinity purification followed by Sephacryl S-100 gel
filtration resulted in APEX peptide with MW 36 KDa, which exhibited AP DNA repair
activity (8,7000 EU/mg protein). N-ethylmaleimide (0.1 mM) or AMP (0.98 mM)
inhibited APEX activity by 50% and kinetic analysis indicated that the
recombinant APEX (rAPEX) had a Km value of 0.022 microM (AP sites for AP DNA) and
the Ki value was 0.48 mM for AMP. These results indicated that E. coli cells
expressing biologically active GST-APEX were resistant to the cell damage caused
by chemical carcinogens and that rAPEX purified from E. coli cells transformed
with APEX cDNA-inserted translation vector was similar to native APEX in some
properties.
PMID- 10198609
TI - Enzyme histochemical study of germanium dioxide-induced mitochondrial myopathy in
rats.
AB - The purpose of this study were 1) to determine the earliest pathological changes
of germanium dioxide (GeO2)-induced myopathy; 2) to determine the pathomechanism
of GeO2-induced myopathy; and 3) to determine the minimal dose of GeO2 to induce
myopathy in rats. One hundred and twenty five male and female Sprague-Dawley
rats, each weighing about 150 gm, were divided into seven groups according to
daily doses of GeO2. Within each group, histopathological studies were done at 4,
8, 16, and 24 weeks of GeO2 administration. Characteristic mitochondrial myopathy
was induced in the groups treated daily with 10 mg/kg of GeO2 or more. In
conclusion, the results were as follows: 1) The earliest pathological change on
electron microscope was the abnormalities of mitochondrial shape, size and
increased number of mitochondria; 2) The earliest pathological change on light
microscope was the presence of ragged red fibers which showed enhanced
subsarcolemmal succinate dehydrogenase and cytochrome c oxidase reactivity; 3)
GeO2 seemed to affect the mitochondrial oxidative metabolism of muscle fibers; 4)
GeO2 could induce mitochondrial myopathy with 10 mg/kg of GeO2 for 4 weeks or
less duration in rats.
PMID- 10198610
TI - Malignant granular cell tumor at the retrotracheal space.
AB - We report a case of an extremely rare neoplasm, malignant granular cell tumor
(MGCT). The patient was a 21-year-old woman, who was 5 months pregnant. The tumor
occurred in the retrotracheal space, extending from the level of the larynx to
the thoracic inlet. In addition, there were multiple, variable-sized tumor
nodules within both lung fields on chest CT scan. Histologically, tissue biopsied
from the periphery of the tumor consisted of solid sheets of large ovoid cells
with ample, eosinophilic cytoplasm, eccentric nuclei, and prominent nucleoli.
Each cell showed slight atypism of the nuclei. There was a focal necrosis at the
periphery of the lesion. These cells stained strongly for S-100 protein, neuron
specific enolase (NSE) and CD68. On electron microscopy, the tumor cells
contained autophagic vacuoles. The patient refused further treatment and died 7
months later. The exact cause of death was not known. Until now, the diagnosis of
MGCTs has been made only when metastasis and an aggressive clinical course are
identified, although some observers advocate that some histologic features such
as nuclear pleomorphism, necrosis, and the presence of any mitotic activity are
indicative of malignancy. These histologic findings are not easily detectable in
every case of MGCT, as in our case. So the diagnosis of a MGCT should be
considered in cases with aggressive clinical findings and some histologic
features, such as necrosis, nuclear atypism, and mitotic activities, which could
suggest the malignant behavior of this neoplasm.
PMID- 10198611
TI - Traumatic hemipelvectomy before body image has developed.
AB - Traumatic hemipelvectomy is rarely observed because very few patients have
survived from the initial trauma. We describe one male child who survived from
this massive trauma with a good functional outcome. The boy was 28 months old
when he was accidentally struck by a truck. He had severe open trauma of the
pelvis and hemorrhage of the left lower limb. Amputation of the left hemipelvis,
colostomy, cystostomy and removal of the left avulsed testicle were performed.
Once healing had been achieved, he was transferred to our Department of Physical
Medicine and Rehabilitation and rehabilitative management was begun, including
prosthetic measurement and psychologic intervention for the patient and his
parents. For 13 years of long-term follow-up, his prosthesis was readjusted
annually. Now he is a 16-year-old middle school student. He is functioning
remarkably well with a prosthesis. The psychologic report shows that he is
emotionally stable and has good scholastic performance. Although hemipelvectomy
appears to be a radical procedure in children, the potential for rehabilitation
in a group of children before body image has developed appears to be unexpectedly
good.
PMID- 10198612
TI - Villous adenoma of the bile ducts: a case report and a review of the reported
cases in Korea.
AB - Villous adenomas are benign epithelial lesions with malignant potential which can
occur at any site in the gastrointestinal tract. They are usually encountered in
the rectum and colon, less frequently in the small bowel and very rarely in the
biliary trees. Nine cases of bile duct villous adenomas have been reported in the
literature. However, 4 cases of bile duct villous adenomas have been reported in
the Korean literature. Recently, we experienced a case of villous adenoma in the
common hepatic duct in a 77-year-old man presenting with obstructive jaundice in
which preoperative histologic diagnosis of villous adenoma played a critical role
in managing this patient. Herein, we present a case report of bile duct villous
adenoma and a review of the reported cases in Korea to help define and manage
this rare disease entity in the bile ducts. In addition, confusing nomenclature
of bile duct adenomas is discussed.
PMID- 10198613
TI - Reduced chest expansion in primary fibromyalgia syndrome.
PMID- 10198614
TI - Derivative chromosome 17 in a case of Burkitt lymphoma with 8;14 translocation.
AB - A complex chromosome rearrangement present in a B-cell line established from a
patient with Burkitt lymphoma was studied by using fluorescence in situ
hybridization (FISH) and immunocytochemistry techniques. The rearranged
chromosome (der17) was apparently composed of 17q, of a partially deleted 17p,
and of other material of chromosome 17p origin that was interspersed with regions
without any clear banding pattern. der(17) contained a functional ch17 centromere
and two additional centromeres of unknown origin that were inactive by all
evidence. By FISH analysis with a TP53 probe, a signal could be demonstrated on
the normal ch17, but not on the rearranged chromosome, a finding which indicates
that 17p deletion caused a concurrent loss of one of the two TP53 alleles. The
marker chromosome was previously observed in some of the malignant cells obtained
from the patient's peripheral blood. These observations therefore indicate that
cells with this specific rearrangement were generated in vivo and subsequently
selected. This rearrangement is likely to have conferred a selective growth
advantage to a subclone present in the original malignant cell population.
PMID- 10198615
TI - Detection of t(12;21) in childhood acute lymphoblastic leukemia by fluorescence
in situ hybridization.
AB - Metaphase preparations from 36 patients with acute lymphoblastic leukemia (ALL)
have been retrospectively screened by fluorescence in situ hybridization (FISH)
to determine the incidence of translocation (12;21) and the potential usefulness
of FISH as an adjunct to conventional cytogenetic analysis. With the use of
specific chromosome paints, 4 of 31 patients with B-lineage childhood ALL (13%)
demonstrated rearrangements of chromosomes 12 and 21, and therefore, were
considered to harbor the translocation, which had not previously been detected by
conventional karyotyping. However, none of these positive cases revealed the
standard reciprocal t(12;21)(p12;q22) as the sole abnormality involving
chromosomes 12 and 21. The study confirms the feasibility and advantages of
introducing FISH screening for t(12;21) in pediatric ALL cases and demonstrates
the usefulness of FISH screening as a backup to concurrent cytogenetic analysis
to resolve variant translocations and aberrant results. The presence of t(12;21)
has also been correlated to clinical data to assess the prognostic significance
of this translocation on its own or in association with other prognostic
features.
PMID- 10198616
TI - Dermatofibrosarcoma protuberans harboring t(9;22)(q32;q12.2).
AB - More than 20 cases of dermatofibrosarcoma protuberans (DFSP) exhibiting
chromosomal abnormalities have been reported. Approximately three fourths of
these tumors have harbored supernumerary ring chromosomes, which have been
suggested to be specific for this tumor. However, a small number of DFSPs with
translocations such as t(2;17), t(X;7), and t(17;22) have recently been reported.
We report a DFSP arising in a 23-year-old woman which unexpectedly exhibited the
balanced translocation, t(9;22)(q32;q12.2) as the only anomaly with G-band
technique. Dual-color fluorescence in situ hybridization (FISH) confirmed these
cytogenetic findings. Similar to that previously reported for DFSPs with
translocations, the present tumor also lacked ring chromosomes.
PMID- 10198617
TI - BCR/ABL translocation in adult acute lymphoblastic leukemia: a comparison of
conventional and interphase cytogenetic studies.
AB - Twenty-four adult Chinese patients with de novo acute lymphoblastic leukemia
(ALL) were studied for the BCR/ABL translocation using both conventional
cytogenetics and fluorescence in situ hybridization (FISH). Eight (33%) patients
had the translocation as shown by FISH and all were B-lineage ALL (8/19, 42%).
Conventional cytogenetics revealed a t(9;22)(q34;q11) in six of them, but was
either unsuccessful, or not done in the other two. Seven of the eight positive
cases (88%) showed a breakpoint at the minor breakpoint cluster region (m-BCR),
which was confirmed by reverse transcriptase polymerase chain reaction (RT-PCR).
To conclude, the frequency of BCR/ABL translocation in Chinese patients with de
novo ALL is comparable to patients in the Western hemisphere, in contrast to a
previous report. The predominance of m-BCR/ABL fusion among these Chinese
patients with BCR/ABL translocation is also similar to patients in the Western
population. Fluorescence in situ hybridization is a sensitive, specific and
relatively simple technique for demonstrating this important unfavorable
prognostic marker in ALL, even in a routine service laboratory setting.
PMID- 10198618
TI - Hemangioendothelioma of bone in a patient with a constitutional supernumerary
marker.
AB - A 13-year old girl was diagnosed as having a bone hemangioendothelioma.
Cytogenetic studies identified the presence of a small supernumerary marker
chromosome in this patient. Classical cytogenetic methods using G-, C-, Ag-NOR
banding were supplemented by spectral karyotyping (SKY) and fluorescence in situ
hybridization to reveal a karyotype 47,XX,+mar.ish der(22)(D22S543+) karyotype in
cells derived from the tumor and lymphocytes. These findings suggest that the
supernumerary marker chromosome originated from the proximal centromeric region
of chromosome 22, and that trisomy of the region 22q11 was not associated with
adverse phenotypic effects, but that the presence of trisomy 22q11 may be related
to the development of this tumor.
PMID- 10198619
TI - Physical mapping of a tandem duplication on the long arm of chromosome 7
associated with a multidrug resistant phenotype.
AB - Both the expression of the multidrug transporter, P-glycoprotein (Pgp), and
abnormalities of the long arm of chromosome 7 have been shown to be adverse
prognostic indicators in acute leukemias. In this study, a clonal duplication,
dup(7)(q11.1q31.1), inherited with the classical multidrug resistant phenotype in
a drug-resistant derivative of a human T-cell leukemia cell line was
characterized. The position of the duplication was of interest as the gene which
encodes Pgp, MDR1, is located on the long arm of chromosome 7 at position 7q21.1.
Fluorescence in situ hybridization (FISH) analysis with a chromosome 7-specific
painting probe confirmed the composition of the abnormal chromosome. A YAC clone
hybridizing to the MDR1 locus confirmed that this gene was located within the
duplicated region of the derivative chromosome. With a panel of well
characterized YAC clones, the duplicated segment was found to be a direct tandem
duplication, somewhat larger than estimated by conventional cytogenetics. The
proximal and distal breakpoints of the abnormality were located and a YAC clone
spanning the distal breakpoint was identified. This clone is of particular
interest, as it harbors the markers D7S523 and D7S471, close to which a putative
tumor suppressor gene is thought to lie. Further examination of the breakpoint
region may therefore illuminate the mechanism of Pgp upregulation as well as
providing information about a tumor suppressor gene.
PMID- 10198620
TI - Changes of chromosomes 1, 3, 6, and 11 in metastatic effusions arising from
breast and ovarian cancer.
AB - This cytogenetic study deals with cell material obtained from 15 pleural fluids
from 11 patients with breast cancer and 27 ascitic fluids from 16 patients with
ovarian cancer; in addition, 8 pleural, 5 ascitic, and 1 pericardial fluid from
patients with tuberculosis, liver cirrhosis, and heart insufficiency, were
studied. Using mainly direct methods, as well as short-term cell cultures, the
chromosome spreads were GTG-banded. Cancerous biopsies showed a plethora of
numerical and structural chromosome anomalies and exhibited broad aneuploidy.
Chromosomes participating more often in numerical and structural aberrations were
1, 3, 6, 7, 8, 9, 11, 12, and 17. This study provides further cytogenetic
evidence for the involvement of these chromosomes in breast and ovarian
malignancy.
PMID- 10198621
TI - Cytogenetic findings in five patients with hairy cell leukemia.
AB - We studied five cases of hairy cell leukemia (HCL) using conventional
cytogenetics. All patients were diagnosed with typical HCL. Chromosome analysis
was carried out on a 72-hour culture of peripheral blood. Phytohemagglutinin
(PHA) mitogen was used. Clonal chromosome abnormalities were found in 2/5
patients (40%), a complex abnormality being identified in one of them. The
chromosomes involved were: 1, 6, 7, 8, and 17. No patient showed trisomy 12 or a
14q+. An interesting result was the finding of del(7)(q32) as a sole anomaly.
PMID- 10198622
TI - Clinical significance of cytogenetic findings at diagnosis and in remission in
childhood and adult acute lymphoblastic leukemia: experience from India.
AB - We report cytogenetic findings in 114 patients of acute lymphoblastic leukemia
(ALL), which includes 78 children (< or = 15 years) and 36 adults (16-60 years).
Chromosome aberrations were detected in 109 (95%) cases. A lower frequency of
hyperdiploidy (15%) in children and a higher frequency of hypodiploidy both in
children (38.4%) and adults (44.4%) were found, in contrast to literature.
Translocations were detected in one third of adult and pediatric cases. The
incidence of t(9;22) was comparatively low in adults (7.7%). Frequency of t(1:19)
was also low in overall ALL cases. Various other recurrent abnormalities such as
del(6q), abn(11q23), i(9p), abn(12q13), del(7q), and i(17q) were seen in our
cases; a striking difference in the incidence of del(6q) (41%) and abn(11q23)
(30%) was found in our series versus reported literature. Ploidy distribution
indicated association of pseudo- and hypodiploidy with B-lineage, and
hypodiploidy with T-lineage in children. The occurrence of del(6q) was more
frequent in pediatric ALL with highly aberrant pattern and also with
lymphadenopathy. Abn(11q23) was found to be early-B and pre-B specific. Kaplan
Meier analysis of overall survival revealed prognostic value of sex, FAB,
immunophenotype, and cytogenetic findings. Females and T-ALL patients had a
better prognosis, whereas males and B-ALL patients had poor outcome in overall
and pediatric age groups. Prognostic evaluation of cytogenetics indicated
translocations as an independent high-risk predictor in childhood (P < 0.008) and
adult ALL (P < 0.01). Childhood ALL with t(8;14) and t(4;11) and adults with
t(9;22) had poor survival. Cytogenetics of remission marrows demonstrated
disappearance of abnormal clones in 31.4%, and expansion in normal clones in 50%
of patients. Persistence of original clones and development of new clones were
observed in 20% and 33% of patients, respectively; whereas karyotype evolution
was identified in 10% of patients. The prognostic significance of cytogenetic
findings at diagnosis, and differential cytogenetic response in so-called
clinical remission in our study indicated the utmost need for more intensive
therapy for eradication of resistant clones, and necessity of sequential
cytogenetic follow-up in these patients for identification of minimal residual
disease.
PMID- 10198623
TI - Two new cases of papillary renal cell carcinoma with t(X;1)(p11;q21) in females.
AB - Two cases of papillary renal cell carcinoma (RCC) with a karyotype
46,X,t(X;1)(p11.2;q21) in two female patients aged 9 and 29 years are reported.
These observations, and the review of the 17 reported cases with a translocation
at band Xp11 confirm that this abnormality delineates a clinicopathological
entity within the classical papillary RCC, characterized by the early age of
occurrence and, probably, distinct histological features. Including these two new
female cases, the sex ratio in cases with t(X;1) appears similar to that observed
in the other papillary RCC.
PMID- 10198624
TI - Polyploidization and losses of chromosomes 1, 2, 6, 10, 13, and 17 in three cases
of chromophobe renal cell carcinomas.
AB - Clonal chromosome aberrations identified after short-term culture are presented
for three cases of chromophobe renal cell carcinomas (RCC). All tumors revealed
abnormal karyotypes with a varying proportion of polyploid tumor cells. Common
numerical abnormalities were combined losses of chromosomes 1, 2, 6, 10, 13, and
17. Clonal karyotypic evolution was demonstrated in one case in which several
related clones could be identified. An additional balanced translocation
t(3;14)(p24;q22) observed in this case proved to be of constitutional nature by
cytogenetic analysis of normal kidney cells and peripheral blood lymphocytes.
These cytogenetic findings provide further evidence that chromophobe renal cell
carcinomas are characterized by a highly specific combination of chromosomal
losses most commonly including chromosomes 1, 2, 6, 10, 13, and 17.
PMID- 10198625
TI - Translocation (2;3)(p21;q26) as the sole anomaly in a case of primary
myelofibrosis.
AB - Translocation t(2p;3q) is a rare but recurrent finding in myeloid disorders. We
present the first case of primary myelofibrosis with t(2;3)(p21;q26) as the sole
chromosomal anomaly. The comparison with the 11 other previously published
myeloid-associated t(2p;3q) cases confirms that this nonrandom translocation
involves a pluripotent stem cell and is associated with a poor prognosis.
PMID- 10198626
TI - Three measures of mutagen sensitivity in a cancer-free population.
AB - Different individuals appear to respond differently to the same carcinogen, and
different mutagens act differently on cells. We conducted mutagen sensitivity
assays by using three mutagens (bleomycin, a radiomimetic agent; 4-nitroquinoline
1-oxide [4-NQO], an ultraviolet light mimetic agent; and benzo[a]pyrene diol
epoxide [BPDE], a tobacco mutagen) in parallel in healthy human subjects to
determine the relationships among these assays. Our results showed that the mean
breaks per cell values (b/c) (+/- SD) for bleomycin, 4-NQO, and BPDE sensitivity
were 0.49 (+/- 0.26), 0.53 (+/- 0.30), and 0.66 (+/- 0.41), respectively. Age,
sex, smoking status, and family history of cancer were not correlated with any of
these mutagen sensitivities. Also, there was no correlation between bleomycin and
4-NQO or 4-NQO and BPDE sensitivity, but a weak correlation between bleomycin and
BPDE was observed (correlation coefficient = 0.289; P = 0.001). When the 75th
percentile of b/c was used as a cutoff point in each assay, only one individual
(1.8%) was sensitive to all three mutagens. Ten individuals (17.9%) were
sensitive to two mutagens, 20 (35.7%) to one mutagen, and 25 (44.6%) to none of
three mutagens. Our study suggests that these three mutagens may involve
different DNA damage and repair pathways. The lack of correlation between the
assay results may indicate the necessity of using a battery of mutagen
sensitivity tests to refine our ability to identify a subpopulation at high
cancer risk.
PMID- 10198627
TI - A case of chronic neutrophilic leukemia with deletion (11)(q23).
AB - We report a case of chronic neutrophilic leukemia (CNL) in a 68-year-old man.
Karyotype showed a clonal abnormality, never described before in CNL:
46,XY,del(11)(q23). Southern blot analysis of the MLL gene did not reveal any
rearrangement, and reverse transcriptase polymerase chain reaction (RT-PCR)
analysis did not show any fusion of BCR-ABL. Treatment with hydroxyurea and
cytosine arabisonide was ineffective.
PMID- 10198628
TI - A thymoma with clonal complex chromosome abnormalities.
PMID- 10198629
TI - Helicobacter pylori attaches to NeuAc alpha 2,3Gal beta 1,4 glycoconjugates
produced in the stomach of transgenic mice lacking parietal cells.
AB - Helicobacter pylori infection of the human stomach is associated with altered
acid secretion, loss of acid-producing parietal cells, and, in some hosts,
adenocarcinoma. We have used a transgenic mouse model to study the effects of
parietal cell ablation on H. pylori pathogenesis. Ablation results in
amplification of the presumptive gastric epithelial stem cell and its immediate
committed daughters. The amplified cells produce sialylated oncofetal
carbohydrate antigens that function as receptors for H. pylori adhesins.
Attachment results in enhanced cellular and humoral immune responses. NeuAc alpha
2,3Gal beta 1,4 glycoconjugates may not only facilitate persistent H. pylori
infection in a changing gastric ecosystem, but by promoting interactions with
lineage progenitors and/or initiated cells contribute to tumorigenesis in
patients with chronic atrophic gastritis.
PMID- 10198630
TI - Brefeldin A acts to stabilize an abortive ARF-GDP-Sec7 domain protein complex:
involvement of specific residues of the Sec7 domain.
AB - We demonstrate that the major in vivo targets of brefeldin A (BFA) in the
secretory pathway of budding yeast are the three members of the Sec7 domain
family of ARF exchange factors: Gea1p and Gea2p (functionally interchangeable)
and Sec7p. Specific residues within the Sec7 domain are important for BFA
inhibition of ARF exchange activity, since mutations in these residues of Gea1p
(sensitive to BFA) and of ARNO (resistant to BFA) reverse the sensitivity of each
to BFA in vivo and in vitro. We show that the target of BFA inhibition of ARF
exchange activity is an ARF-GDP-Sec7 domain protein complex, and that BFA acts to
stabilize this complex to a greater extent for a BFA-sensitive Sec7 domain than
for a resistant one.
PMID- 10198631
TI - The proapoptotic activity of the Bcl-2 family member Bim is regulated by
interaction with the dynein motor complex.
AB - Bcl-2 family members that have only a single Bcl-2 homology domain, BH3, are
potent inducers of apoptosis, and some appear to play a critical role in
developmentally programmed cell death. We examined the regulation of the
proapoptotic activity of the BH3-only protein Bim. In healthy cells, most Bim
molecules were bound to LC8 cytoplasmic dynein light chain and thereby
sequestered to the microtubule-associated dynein motor complex. Certain apoptotic
stimuli disrupted the interaction between LC8 and the dynein motor complex. This
freed Bim to translocate together with LC8 to Bcl-2 and to neutralize its
antiapoptotic activity. This process did not require caspase activity and
therefore constitutes an initiating event in apoptosis signaling.
PMID- 10198632
TI - twin of eyeless, a second Pax-6 gene of Drosophila, acts upstream of eyeless in
the control of eye development.
AB - The Drosophila Pax-6 gene eyeless (ey) plays a key role in eye development. Here
we show tht Drosophila contains a second Pax-6 gene, twin of eyeless (toy), due
to a duplication during insect evolution. Toy is more similar to vertebrate Pax-6
proteins than Ey with regard to overall sequence conservation, DNA-binding
function, and early expression in the embryo, toy and ey share a similar
expression pattern in the developing visual system, and targeted expression of
Toy, like Ey, induces the formation of ectopic eyes. Genetic and biochemical
evidence indicates, however, that Toy functions upstream of ey by directly
regulating the eye-specific enhancer of ey. Toy is therefore required for
initiation of ey expression in the embryo and acts through Ey to activate the eye
developmental program.
PMID- 10198633
TI - Structural basis for paramyxovirus-mediated membrane fusion.
AB - Paramyxoviruses are responsible for significant human mortality and disease
worldwide, but the molecular mechanisms underlying their entry into host cells
remain poorly understood. We have solved the crystal structure of a fragment of
the simian parainfluenza virus 5 fusion protein (SV5 F), revealing a 96 A long
coiled coil surrounded by three antiparallel helices. This structure places the
fusion and transmembrane anchor of SV5 F in close proximity with a large
intervening domain at the opposite end of the coiled coil. Six amino acids,
potentially part of the fusion peptide, form a segment of the central coiled
coil, suggesting that this structure extends into the membrane. Deletion mutants
of SV5 F indicate that putative flexible tethers between the coiled coil and the
viral membrane are dispensable for fusion. The lack of flexible tethers may
couple a final conformational change in the F protein directly to the fusion of
two bilayers.
PMID- 10198634
TI - Evidence that a single replication fork proceeds from early to late replicating
domains in the IgH locus in a non-B cell line.
AB - In non-B cell lines, like the murine erythroleukemia cell line (MEL), the most
distal IgH constant region gene, C alpha, replicates early in S; other heavy
chain constant region genes, joining and diversity segments, and the most
proximal Vh gene replicate successively later in S in a 3' to 5' direction
proportional to their distance from C alpha. In MEL, replication forks detected
in the IgH locus also proceed in the same 3' to 5' direction for approximately
400 kb, beginning downstream of the IgH 3' regulatory region and continuing to
the D region, as well as within the Vh81X gene. Downstream of the initiation
region is an early replicating domain, and upstream of Vh81X is a late
replicating domain. Hence, the gradual transition between early and late
replicated domains can be achieved by a single replication fork.
PMID- 10198635
TI - Intermolecular V(D)J recombination is prohibited specifically at the joining
step.
AB - V(D)J recombination, normally an intramolecular process, assembles immunoglobulin
and T cell receptor genes from V, D, and J coding segments. Oncogenic chromosome
translocations can result from aberrant rearrangements, such as occur in
intermolecular V(D)J recombination. How this is normally prevented remains
unclear; DNA cleavage, joining, or both could be impaired when the recombination
signal sequences (RSS) are located in trans, on separate DNA molecules. Here, we
show that both trans cleavage and joining of signal ends occur efficiently in
vivo. Unexpectedly, trans joining of coding ends is severely impaired (100-to
1000-fold), indicating that protection against intermolecular V(D)J recombination
is established at the joining step. These findings suggest a novel surveillance
mechanism for eliminating cells containing aberrant V(D)J rearrangements.
PMID- 10198636
TI - Internuclear gene silencing in Phytophthora infestans.
AB - Transformation of the diploid oomycete plant pathogen Phytophthora infestans with
antisense, sense, and promoter-less constructs of the coding sequence of the
elicitin gene inf1 resulted in transcriptional silencing of both the transgenes
and the endogenous gene. Since heterokaryons obtained by somatic fusion of an
inf1-silenced transgenic strain and a wild-type strain displayed stable gene
silencing, inf1 silencing is dominant and acts in trans. Inf1 remained silenced
in nontransgenic homokaryotic progeny from the silenced heterokaryons, thereby
demonstrating that the presence of transgenes is not essential for maintaining
the silenced status of the endogenous inf1 gene. These findings support a model
reminiscent of paramutation and involving a trans-acting factor that is capable
of transferring a silencing signal between nuclei.
PMID- 10198637
TI - HUA1 and HUA2 are two members of the floral homeotic AGAMOUS pathway.
AB - The identities of the four floral organ types in an Arabidopsis flower are
specified by the combinatorial activities of the floral homeotic A, B, and C
function genes; AGAMOUS is the only known C function gene. We have identified two
genes that interact with AG in the specification of floral structure, HUA1 and
HUA2, from a screen for enhancers of a weak ag allele, ag-4. HUA1 and HUA2 are
involved in all aspects of AG function. HUA2 encodes a novel protein that
contains nuclear localization signals and signature motifs that suggest HUA2,
like AG, may be a transcription factor. Molecular analyses suggest that HUA2 (and
possibly HUA1) acts to facilitate AG action at the same hierarchical level as AG.
PMID- 10198638
TI - Identity between TRAP and SMCC complexes indicates novel pathways for the
function of nuclear receptors and diverse mammalian activators.
AB - The human thyroid hormone receptor-associated protein (TRAP) complex, an earlier
described coactivator for nuclear receptors, and an SRB- and MED-containing
cofactor complex (SMCC) that mediates activation by Gal4-p53 are shown to be
virtually the same with respect to specific polypeptide subunits, coactivator
functions, and mechanisms of action (activator interactions). In parallel with
ligand-dependent interactions of nuclear receptors with the TRAP220 subunit, p53
and VP16 activation domains interact directly with a newly cloned TRAP80 subunit.
These results indicate novel pathways for the function of nuclear receptors and
other activators (p53 and VP16) through a common coactivator complex that is
likely to target RNA polymerase II. Identification of the TRAP230 subunit as a
previously predicted gene product also suggests a coactivator-related
transcription defect in certain disease states.
PMID- 10198639
TI - Terminal exon definition occurs cotranscriptionally and promotes termination of
RNA polymerase II.
AB - Analysis of nascent transcription from the human epsilon- and beta-globin genes
shows that transcriptional termination occurs within 1.5 kb of the poly(A) site
and is dependent on the presence of functional poly(A) signals. Even so,
transcripts that have not been cleaved at the poly(A) site are detected up to the
termination region, suggesting that there is a kinetic lag between transcription
over the poly(A) signal and its effect on transcriptional termination.
Surprisingly, mutation of the splice acceptor (SA) of the beta-globin IVS2 also
abolishes transcriptional termination. Our results emphasize the interconnection
of transcription and RNA processing by showing that the enhancement of 3' end
processing by the terminal splice acceptor occurs cotranscriptionally.
PMID- 10198640
TI - EM visualization of transcription by RNA polymerase II: downstream termination
requires a poly(A) signal but not transcript cleavage.
AB - We have used EM visualization of active genes on plasmid vectors in Xenopus
oocyte nuclei to investigate the relationship between poly(A) signals and RNA
polymerase II transcription termination. Although a functional poly(A) signal is
required for efficient termination, cotranscriptional RNA cleavage at the poly(A)
site is not. Furthermore, the phenomena of termination and cotranscriptional RNA
cleavage can be uncoupled, and the efficiency of both varies independently on
different copies of the same plasmid template in the same oocyte nucleus. The
combined observations are consistent with a scenario in which there is template
specific addition to Pol II (presumably at the promoter) of elongation and/or RNA
processing factors, which are altered upon passage through a poly(A) signal,
resulting in termination and, in some cases, cotranscriptional RNA cleavage.
PMID- 10198641
TI - Centrosome amplification and a defective G2-M cell cycle checkpoint induce
genetic instability in BRCA1 exon 11 isoform-deficient cells.
AB - Germline mutations of the Brca1 tumor suppressor gene predispose women to breast
and ovarian cancers. To study mechanisms underlying BRCA1-related tumorigenesis,
we derived mouse embryonic fibroblast cells carrying a targeted deletion of exon
11 of the Brca1 gene. We show that the mutant cells maintain an intact G1-S cell
cycle checkpoint and proliferate poorly. However, a defective G2-M checkpoint in
these cells is accompanied by extensive chromosomal abnormalities. Mutant
fibroblasts contain multiple, functional centrosomes, which lead to unequal
chromosome segregation, abnormal nuclear division, and aneuploidy. These data
uncover an essential role of BRCA1 in maintaining genetic stability through the
regulation of centrosome duplication and the G2-M checkpoint and provide a
molecular basis for the role of BRCA1 in tumorigenesis.
PMID- 10198642
TI - Molecular recognition of fatty acids by peroxisome proliferator-activated
receptors.
AB - The peroxisome proliferator-activated receptors (PPARs) are nuclear receptors for
fatty acids (FAs) that regulate glucose and lipid homeostasis. We report the
crystal structure of the PPAR delta ligand-binding domain (LBD) bound to either
the FA eicosapentaenoic acid (EPA) or the synthetic fibrate GW2433. The
carboxylic acids of EPA and GW2433 interact directly with the activation function
2 (AF-2) helix. The hydrophobic tail of EPA adopts two distinct conformations
within the large hydrophobic cavity. GW2433 occupies essentially the same space
as EPA bound in both conformations. These structures provide molecular insight
into the propensity for PPARs to interact with a variety of synthetic and natural
compounds, including FAs that vary in both chain length and degree of saturation.
PMID- 10198643
TI - Distinct roles for CTD Ser-2 and Ser-5 phosphorylation in the recruitment and
allosteric activation of mammalian mRNA capping enzyme.
AB - Capping is targeted to pre-mRNAs through binding of the guanylyltransferase
component of the capping apparatus to the phosphorylated CTD of RNA polymerase
II. We report that mammalian guanylyltransferase binds synthetic CTD peptides
containing phosphoserine at either position 2 or 5 of the YSPTSPS heptad repeat.
CTD peptides containing Ser-5-PO4 stimulate guanylyltransferase activity by
enhancing enzyme affinity for GTP and increasing the yield of the enzyme-GMP
intermediate. A CTD peptide containing Ser-2-PO4 has no effect on
guanylyltransferase activity. This implies an allosteric change in
guanylyltransferase conformation that is specified by the position of
phosphoserine in the CTD. Stimulation of guanylyltransferase increases with the
number of Ser-5-phosphorylated heptads. Our results underscore how mRNA
production may be regulated by the display of different CTD phosphorylation
arrays during transcription elongation.
PMID- 10198644
TI - Imaging of coronary artery calcification. Its importance in assessing
atherosclerotic disease.
AB - Coronary artery calcification is a marker for atherosclerotic disease. The
calcifications frequently occur early in the disease process and often before the
development of luminal narrowing or cardiac events. Electron beam CT has a high
accuracy in detecting calcifications, and thus has prognostic value in predicting
luminal narrowing and future cardiac events.
PMID- 10198645
TI - Coronary MR angiography.
AB - MR angiography of the coronary arteries became possible in 1991 with the
development of a new group of fast MR imaging sequences. Although the role of
coronary MR angiography in screening for coronary artery lesions has not yet been
established, coronary MR angiography already has been very successful in the
detection of coronary artery variants and the imaging of coronary stents and
bypass grafts. Variants of these new MR imaging techniques also can quantitate
velocity in native coronary arteries. Several generations of coronary MR
angiographic techniques exist; all techniques use EKG-triggering. The use of MR
contrast agents appears to further improve all techniques. Technical progress and
changes in this subfield of cardiac MR imaging have been so fast that large-scale
preclinical trials have not been conducted with the majority of the first and
second generation coronary MR angiographic pulse sequences as known today. This
article reviews the development of these new cardiac MR imaging techniques and
the initial successes with clinical application using commercial MR scanners.
PMID- 10198646
TI - Valvular heart disease.
AB - Congenital and acquired valvular disease remains a frequent cause of morbidity
and mortality. It presents a diagnostic challenge in all age groups, and often
occurs in conjunction with other types of heart disease. Traditional chest
radiography provides the earliest opportunity for radiologic diagnosis, hence the
need for skill and knowledge in interpreting the radiographic findings.
Echocardiography with color flow Doppler measurements is frequently the next
modality applied. CT and MR imaging can simultaneously display cardiovascular
morphology with greater spatial resolution than ultrasound, and at the same time
provide quantitative assessment of cardiac function. The role of diagnostic
imaging is therefore crucial, both for primary diagnosis and in the management of
valvular heart disease. Furthermore, it is fundamental in evaluating the results
of all forms of interventional therapy.
PMID- 10198647
TI - Ventricular function.
AB - Multiple modalities contribute to the evaluation of ventricular function. The
role of cineangiography, echocardiography, MR imaging, ultrafast CT, and nuclear
medicine continue to evolve and improve our understanding of the physiology and
pathophysiology of ventricular function. This article discusses the use and
limitation of each modality.
PMID- 10198648
TI - Myocardial viability.
AB - This article reviews various means to assess myocardial viability by imaging, and
provides recommendations for current clinical practice. This article also
discusses future directions in assessing myocardial viability.
PMID- 10198649
TI - Radiology of the right ventricle.
AB - RV changes may be generalized into dilatation and hypertrophy. Increased preload
results in ventricular dilatation. Increased afterload causes hypertrophy. Change
in the shape of the RV resulting from increased afterload and myocardial
hypertrophy induces tricuspid regurgitation, which superimposes changes of
chamber dilatation onto those of hypertrophy. Sustained ventricular dilatation
and hypertrophy frequently progresses to RV failure. In these cases, RV systolic
function decreases in association with elevation of RV and right atrial diastolic
pressure. Changes in the wall thickness and shape of the RV are variable, and
depend upon the severity of the volume or pressure load presented, as well as its
duration and rate of progression. Because the RV is an anterior cardiac
structure, it occupies little of any heart border. Therefore, the sensitivity of
plain film examination to RV disease is limited. Inferential diagnosis of RV
disease can often be made based upon identification of other radiographic
changes, notably the state of the pulmonary circulation, and the position of the
heart in the chest. Conventional contrast right ventriculography may be used to
assess the size and position of the RV, as well as associated acquired and
congenital lesions that result in RV dysfunction. Due to the unusual shape of the
RV cavity, however, and the unpredictable manner in which it dilates, accurate
quantitative analysis by this technique is limited. Furthermore, the common
association between RV disease and pulmonary hypertension limits the
applicability of this imaging technique for evaluating patients with RV disease.
Multiplanar MR imaging allows direct demonstration of changes in RV size and wall
morphology. Furthermore, application of Simpson's rule to tomographic slices
acquired at ventricular diastole and systole allows direct, accurate, and
reproducible quantitative analysis of ventricular volume and myocardial mass,
allowing radiographic assessment in patients for diagnosis, as well as
longitudinally during medical management or after surgical treatment for
congenital and acquired diseases that result in RV dysfunction.
PMID- 10198650
TI - Plain film diagnosis of common cardiac anomalies in the adult.
AB - Congenital cardiac lesions in the adult have characteristic roentgen patterns
that should be recognized by the radiologist. In other instances, abnormalities
in the aorta or the position of the organs can indicate the likelihood of
associated cardiac anomalies. An increasing number of congenital cardiac patients
are surviving into adult life because of successful treatment. Some of the
complications of these repairs can be recognized on routine chest films.
PMID- 10198651
TI - MR imaging of adult patients with congenital heart disease.
AB - Although the incidence of congenital heart disease remains constant among
newborns, improved medical and surgical techniques have dramatically prolonged
life expectancy and produced a new, growing group of patients harboring these
lesions: adults with congenital heart disease. Conventional imaging techniques in
these patients may be limited because of patient size, chest configuration, or
poor ventricular function. MR imaging provides a noninvasive means of directly
demonstrating their developmental abnormalities and the sequelae of
pathophysiologic changes caused by these lesions. Combined use of spin echo and
gradient reversal echo acquisition techniques allows complete evaluation of
cardiac morphology and function in these patients. An new medical and surgical
therapies prolong the lives of these patients, the role of MR imaging for
physiologic assessment and surgical planning will expand further.
PMID- 10198652
TI - Interventional procedures for congenital heart disease.
AB - Interventional techniques available for use in treating congenital heart disease
include balloon dilation of valves and vessels, stent placement and coil
embolization of collaterals, patent ducts and other arterial fistulae. In
addition, a variety of devices for closure of atrial and ventricular septal
defects and patent ducts currently are under investigation. Radiofrequency
ablation of arrhythmias also is applicable to the pediatric population.
PMID- 10198653
TI - How does managed care manage the frail elderly? The case of hospital readmissions
in fee-for-service versus HMO systems.
AB - OBJECTIVES: This study examined whether hospital readmissions varied among the
frail elderly in managed care versus fee-for-service (FFS) systems. SETTING AND
PARTICIPANTS: Random sample of 450 patients, aged 65 and over, from a large
vertically integrated health care system in San Diego, California. Participants
were receiving physician-authorized home health and survived and 18-month follow
up period. MAIN OUTCOME MEASURES: Multiple logistic regression analyses were used
to conduct comparisons of readmissions and preventable readmissions by plan type.
Two methods to identify preventable readmissions were developed, one based on a
computerized algorithm of service use patterns, and another based on blind
clinical review. RESULTS: The odds of having a preventable hospital readmission
within 90 days of an index admission were 3.51 (P = 0.06) to 5.82 (P = 0.02)
times as high for Medicare HMO enrollees compared to Medicare FFS participants,
depending on the method used to assess preventability. Readmission patterns were
similar for Medicare HMO enrollees and FFS study participants dually enrolled in
Medicare and Medicaid. CONCLUSION: In this group of frail elderly Medicare
beneficiaries, those enrolled in an HMO were more likely to have a preventable
hospital readmission than those receiving care under FFS. These results suggest
that policies promoting stringent approaches to utilization control (e.g., early
hospital discharge, reduced levels of post-acute care, and restricted use of home
health services) may be problematic for the frail elderly.
PMID- 10198654
TI - Validation of self-report of influenza and pneumococcal vaccination status in
elderly outpatients.
AB - OBJECTIVE: To assess the validity of self-reported influenza and pneumococcal
vaccination status. DESIGN: Cross-sectional surveys of outpatients aged 65 years
or older. SETTING: A Veterans Affairs Medical Center (VA) and a community managed
care organization (MCO). Both organizations have organized influenza and
pneumococcal vaccination programs. SUBJECTS: VA subjects included all elderly
respondents to a mailed survey of 500 randomly selected outpatients. MCO subjects
included all respondents to a telephone survey of 300 randomly selected elderly
members of the MCO. MEASUREMENTS: The VA survey was conducted following the 1995
1996 influenza season while the MCO survey was conducted following the 1994-1995
season. Self-report from the mailed survey for VA subjects and from the telephone
survey for MCO subjects was compared to medical record documentation (paper and
computerized combined). RESULTS: The response rate was 77% (n = 369) for the VA
subjects of whom 195 (53%) were aged 65 or older. The response rate for the MCO
subjects was 84% (n = 237). Self-report of influenza vaccination had a
sensitivity (SENS) of 1.0 and a specificity (SPEC) of .79 with a kappa of .72
(95% CI .58-.86) among VA patients. Among MCO patients, self-report of influenza
vaccination had a SENS of .98 and a SPEC of .71 with kappa of .75 (95% CI .69
.89). Self-report of pneumococcal vaccination status among VA patients had a SENS
of .97 and a SPEC of .53 with a kappa of .42 (95% CI .32-.52). Among MCO
patients, self-report of pneumococcal vaccination had a SENS of .90 and a SPEC of
.64 with a kappa of .54 (95% CI .40-.68). A secondary analysis excluding subjects
living outside of the VA's catchment area improved the specificity and indices of
concordance of self-report of both influenza and pneumococcal vaccination. A
secondary analysis of MCO data which excluded subjects who received a
pneumococcal vaccination > 2 years prior to the study also improved concordance
and the negative predictive value of self-report. CONCLUSIONS: Self-report of
influenza vaccination is a highly sensitive and moderately specific measure. Self
report of pneumococcal vaccination is also a highly sensitive but less specific
measure of vaccination status. Lower rates of validity for pneumococcal
vaccination may reflect both less accurate recall, particularly for more distant
vaccination, and less complete documentation in medical records.
PMID- 10198655
TI - Tuberculosis screening in private physicians' offices, Pennsylvania, 1996.
AB - OBJECTIVE: To assess tuberculin skin testing practices of physicians after
community-wide screening of 1400 children exposed to a pediatrician with active
tuberculosis (TB). DESIGN: A self-administered questionnaire. SETTING: Medium
sized city in eastern Pennsylvania. PARTICIPANTS: Pediatricians and family
practitioners seeing pediatric patients. MAIN OUTCOME MEASURES: Percentages of
physicians who followed published recommendations for placement and reading of TB
skin tests published by the American Academy of Pediatrics (AAP) and the Centers
for Disease Control and Prevention (CDC). RESULTS: Questionnaires were completed
by 60/80 (75%) physicians. The 60 physicians had practiced a mean of 17 years
(range 3-38 years), and only one did not do TB skin testing for pediatric
patients. The 59 physicians doing TB skin testing reported routinely tuberculin
testing more than 900 children per month. Only 8/59 (14%) physicians followed
published guidelines for placement and reading of tuberculin tests. Those
physicians screened 158 (17%) of the pediatric patients undergoing TB skin
testing in a typical month. CONCLUSION: In this community where a highly
publicized TB case prompted massive pediatric screening, most physicians seeing
children in private practice do not follow standard TB skin testing guidelines.
Increased understanding of how private-practice physicians learn about and decide
to use recommended standards are needed if tuberculin tests are to be correctly
performed and TB appropriately diagnosed.
PMID- 10198656
TI - Monetary versus nonmonetary incentives for TB skin test reading among drug users.
AB - BACKGROUND: In a prior study, we reported that monetary incentives were effective
in increasing return for tuberculosis (TB) skin test reading. The purpose of this
study was to compare the effects of monetary versus nonmonetary incentives and a
theory-based educational intervention on return for TB skin test reading in a
sample of newly recruited active injection and crack cocaine users, and to
determine the prevalence of TB infection in this sample. METHODS: Active
injection drug and/or crack cocaine users (n = 1,078), recruited using street
outreach techniques, were skin tested for TB. They were randomly assigned to 1 of
5 experimental treatment conditions: $10 cash, grocery store coupons, bus
tokens/fast-food coupons, motivational education, or usual encouragement to
return. Nonmonetary incentives had a $10 value, and all incentives were provided
at return for skin test reading. RESULTS: Ninety-five percent of those who
received $10 returned for skin test reading compared to 86% of those who received
grocery store coupons and 83% of those who received either bus tokens or fast
food coupons. In contrast, only 47% of those who received the educational session
and only 49% of those who received usual encouragement returned for skin test
reading. The prevalence of a positive tuberculin test was 21%, and was similar
for crack cocaine and injection drug users. CONCLUSIONS: Nonmonetary and monetary
incentives dramatically increased the return rate for TB skin test reading among
drug users who are at high risk of TB infection. Nonmonetary incentives were
somewhat less effective than monetary incentives.
PMID- 10198657
TI - Minimum time interval adjustment for 4-3-1 immunization rates among two-year-old
children.
AB - BACKGROUND: The purpose is to determine the administrative validity of the 4-3-1
immunization rates for DPT-OPV-MMR vaccines for 2-year-old children in a
community health status assessment project by accounting for premature
administration of specific vaccine doses according to ACIP recommended minimal
timing intervals. METHODS: A retrospective survey of immunization certificates
was made on a random sample of 1,059 kindergarten enrollees in the county,
including public, private, and parochial schools. The immunization rates by the
crude 4-3-1 counting method were compared with the same method adjusted for
minimal time interval vaccine dosing. RESULTS: By the crude 4-3-1 counting
method, 55.5% of the students had complete immunizations by their second
birthdate, and 11.8% did not meet the minimum interval recommendations on at
least one of 4-3-1 vaccine series. The adjustment for minimum time interval
reduced the percent in compliance with the 4-3-1 counting method by age 2 in the
community to 50.7%. CONCLUSION: The premature timing of vaccine doses is a threat
to the validity of the 4-3-1 counting method. The crude 4-3-1 method over
estimates the completed immunization rates for 2-year-olds in this community
based study by about 4.8%.
PMID- 10198658
TI - Cigar smoking in California: 1990-1996.
AB - BACKGROUND: Cigars have been heavily promoted in recent years. The nature and
extent of the resultant increase in cigar smoking needs to be understood before
the public health implications can be assessed. METHODS: Data are from population
based surveys conducted in California adults (> or = 18 years) in 1990 (n =
24,296) and 1996 (n = 24,266). Trends in current (every day or some days) cigar
use are described for demographic subgroups and by cigarette smoking status.
RESULTS: Current cigar use has doubled in California, from 2.5% in 1990 to 4.9%
in 1996. In 1996, fewer than 5% of cigar smokers smoked cigars daily; essentially
all of the increase was from nondaily use in those under 45 years of age of both
genders, particularly in 18- to 24-year-olds. Among males, increased cigar use
was observed in all racial/ethnic groups except Asians, and was observed in those
with higher educational attainment and higher incomes. In both years, current and
former cigarette smokers had higher rates of cigar use than never smokers, but
the increase in current cigar smoking was observed regardless of cigarette
smoking status. In 1996, daily cigar smokers were more likely to be former
cigarette smokers than nondaily cigar smokers. CONCLUSION: If more people begin
to smoke cigars daily, or if cigar use leads young people to initiate cigarette
smoking or leads former cigarette smokers to relapse to cigarette smoking, the
recent trends in cigar use may have public health implications.
PMID- 10198659
TI - Predictors of smoking cessation in U.S. adolescents.
AB - OBJECTIVE: To identify factors that predict quitting among adolescent smokers.
METHODS: Adolescent smokers aged 12-19 years (N = 633) from the national Teenage
Attitudes and Practices Survey I (1989), were followed up in the Teenage
Attitudes and Practices Survey II (1993). Multiple logistic regression was
applied to identify the predictors of quitting. RESULTS: A total of 15.6% of
adolescent smokers had quit smoking at the follow-up survey four years later.
There was no significant difference in the quit rate by age, gender, or
ethnicity. Five baseline factors were identified in a multivariate analysis as
significant predictors of quitting: frequency of smoking, length of past quit
attempts, self-estimation of likelihood of continuing smoking, mother's smoking
status, and depressive symptoms. The more risk factors the adolescents had, the
less likely they would succeed in quitting. CONCLUSIONS: Quitting smoking by
adolescents is influenced by multiple biological, behavioral, and psychosocial
variables. Identifying these variables can help tailor cessation programs to more
effectively help adolescents quit smoking.
PMID- 10198660
TI - Effects of smoking during pregnancy. Five meta-analyses.
AB - BACKGROUND: The purpose of this study was to estimate, using meta-analysis,
pooled odds ratios for the effects of smoking on five pregnancy complications:
placenta previa, abruptio placenta, ectopic pregnancy, preterm premature rupture
of the membrane (PPROM), and pre-eclampsia. METHODS: Published articles were
identified through computer search and literature review. Five criteria were
applied to those studies initially identified to determine those eligible for the
meta-analysis. A random effects model was applied to derive pooled odds ratios
for the eligible studies for each pregnancy complication. Meta-analyses were
repeated on subsets of the studies to confirm the overall results. RESULTS:
Smoking was found to be strongly associated with an elevated risk or placenta
previa, abruptio placenta, ectopic pregnancy, and PPROM, and a decreased risk of
pre-eclampsia. All pooled odds ratios were statistically significant. The pooled
ratios ranged from 1.58 for placenta previa to 1.77 for ectopic pregnancy. The
pooled odds ratio for pre-eclampsia was 0.51 and all subset analyses confirmed
this seemingly protective effect. CONCLUSIONS: Smoking during pregnancy is a
significant and preventable factor affecting ectopic pregnancy, placental
abruption, placenta previa, and PPROM. The findings of smoking's apparently
protective effect on pre-eclampsia should be balanced with these harmful effects.
In addition, the biological linkage between smoking and pre-eclampsia is not yet
well understood. Pregnant women should be advised to stop smoking in order to
reduce the overall risk of pregnancy complications as well as any risk of adverse
impact on the unborn child.
PMID- 10198661
TI - A multi-state survey of consumer food-handling and food-consumption practices.
AB - INTRODUCTION: In the United States, foodborne infections cause an estimated 6.5
33 million illnesses a year. Also included in the burden of foodborne illnesses
are sequelae such as hemolytic uremic syndrome, Guillain-Barre syndrome, and
reactive arthritis. Surveillance for risky food-handling and food-consumption
practices can be used to identify high-risk populations, develop educational
efforts, and evaluate progress toward risk reduction. DESIGN: In 1995 and 1996,
Behavioral Risk Factor Surveillance System interviews of 19,356 adults in eight
states (1995: Colorado, Florida, Missouri, New York, and Tennessee; 1996:
Indiana, New Jersey, and South Dakota) included questions related to food
handling and/or food-consumption practices. Risky food-handling and food
consumption practices were not uncommon. Overall, 19% of respondents did not
adequately wash hands or cutting boards after contact with raw meat or chicken.
During the previous year, 20% ate pink hamburgers, 50% ate undercooked eggs, 8%
ate raw oysters, and 1% drank raw milk. Men were more likely to report risky
practices than women. The prevalence of most risky behaviors increased with
increasing socioeconomic status. CONCLUSION: Targeted education efforts may
reduce the frequency of these behaviors. Periodic surveillance can be used to
assess effectiveness. In addition to consumer education, prevention efforts are
needed throughout the food chain including on the farm, in processing,
distribution, and at retail.
PMID- 10198662
TI - Predictors of change in children's physical activity over 20 months. Variations
by gender and level of adiposity.
AB - BACKGROUND: Physical activity declines during childhood and determinants of this
decline are poorly understood. The purpose of this prospective study was to
examine modifiable psychological and social correlates of physical activity
change over 20 months. SUBJECTS: 370 girls and 362 boys in public schools,
studied through the 4th and 5th grades. MEASURES: A physical activity index was
computed from child reports, parent reports, and objective activity monitoring.
Predictor variables were assessed by child and parent surveys. RESULTS: In
multiple regressions, after adjustments for demographic variables, psychological
variables explained 4% of the variance in boys' physical activity change, parent
variables explained 8%, and interactions with skinfolds explained 3%, for a total
of 15% (unadjusted). Regarding change in girls' physical activity, psychological
variables explained 3%, parent variables explained 1.5%, and interactions with
skinfold explained 1.5%, for a total of 6% explained variance (unadjusted). There
were differences in predictors among children with high and low levels of body
fat. CONCLUSIONS: Children's preferences for physical activity and frequency of
parents transporting children to activity locations explained significant
proportions of variance for girls and boys. The results support a dynamic model
of the determinants of children's physical activity, but most of the variance was
left unexplained.
PMID- 10198663
TI - Tailored advice on exercise--does it make a difference?
AB - OBJECTIVE: A controlled trial to compare the effectiveness of verbal advice from
a family physician (FP) combined with either "standard" or "tailored" written
information on physical activity in increasing the levels of physical activity in
sedentary patients. DESIGN: Sedentary patients (n = 763) were recruited through
ten family practices and allocated to a control group or one of two intervention
groups. Brief advice on physical activity was given by the FP during the
consultation and either a standard or tailored pamphlet was mailed to the home
address of patients assigned to the intervention groups within two days of their
visit to the FP. RESULTS: The response to follow-up, via a postal survey at one,
six, and twelve months after the index consultation was 70%, 60%, and 57%,
respectively. Treating all nonresponders as sedentary, the results revealed that
although more tailored subjects reported some physical activity at each follow-up
compared with the standard group, these differences were not significant.
Furthermore, there was no significant difference in movement across the stages of
readiness to exercise at follow-up between subjects in the tailored group who
received material targeting their current stage (precontemplation or
contemplation) and the standard group who received generic material that
addressed both stages. CONCLUSION: These findings do not concur with the results
from previous research in the areas of nutrition and smoking cessation where
additional benefits were seen with a tailored intervention. Future research on
the application of the principles of "tailoring" to the promotion of physical
activity should focus on identifying which, if any, physical, social,
psychological or environmental variables should be addressed to produce improved
outcomes over and above the effects of well designed generic materials.
PMID- 10198664
TI - Validation of a self-administered questionnaire to screen for prenatal alcohol
use in Northern Plains Indian women.
AB - OBJECTIVE: This study among American Indian prenatal patients was conducted to
validate a self-administered questionnaire (SAQ) designed to (1) identify women
who had consumed alcohol during pregnancy, (2) identify women who may be at risk
of drinking during pregnancy, and (3) determine the quantity and frequency of
alcohol and other substance use just before and during pregnancy. METHODS: The
validation involved three components: (1) review of the SAQ responses by a public
health nurse; (2) structured patient interview with the research nurse; and (3)
medical record abstraction postpartum. RESULTS: Compared to extensive interview
and medical record data, the SAQ is sensitive (76.6%) and specific (92.8%) in
detecting pregnant women who had consumed alcohol during pregnancy. CONCLUSION:
The SAQ is a useful screening tool for alcohol use in this population.
PMID- 10198665
TI - Relationships between physician advice and tobacco and alcohol use during
pregnancy.
AB - INTRODUCTION: We sought to examine relationships between physician advice and use
of tobacco and alcohol during pregnancy among 683 women in the upper Midwest.
METHODS: Data on risk of substance use during pregnancy were analyzed using
logistic regression analysis. RESULTS: A higher proportion of women used tobacco
(34%) than alcohol (25%) during their most recent pregnancy. Women who received
advice from a physician to abstain from alcohol reported a lower risk of smoking
and drinking during pregnancy than women who did not receive such advice. Risk of
smoking and drinking during pregnancy was also common among women who reported
early onset of alcohol use. CONCLUSIONS: Results suggest that physician advice
regarding alcohol use during pregnancy is protective against maternal smoking and
drinking during pregnancy.
PMID- 10198666
TI - An ounce of prevention ... what are the returns? Second edition, 1999.
AB - CONTEXT: Because human and financial resources are limited, health efforts must
focus on prevention strategies that yield the most benefit for the investment.
Many current strategies identified in the literature offer opportunities to
promote health at a reasonable cost. OBJECTIVE: To present a literature-based
review of evidence demonstrating that prevention can be an effective and wise use
of resources through CDC's An Ounce of Prevention ... What Are the Returns?
Second Edition. DESIGN: Systematic review of cost-effectiveness literature for a
selected group of prevention strategies. SETTING: Prevention strategies relevant
to the U.S. population. RESULTS: Data indicate that the health conditions
considered can be addressed through prevention strategies that are either cost
effective or cost saving. CONCLUSIONS: An Ounce of Prevention ... What Are the
Returns? Second Edition can be used to conveniently access information on
prevention strategies, the diseases and injuries they address, and their cost
effectiveness. It also complements other comprehensive prevention guides.
However, limitations of the available cost-effectiveness studies indicate that
standardized procedures should be followed for studies of all recommended
prevention strategies. Researchers must standardize review procedures to improve
both the quality and comparability of studies.
PMID- 10198667
TI - American College of Preventive Medicine public policy statement. Folic acid
fortification of grain products in the U.S. to prevent neural tube defects.
PMID- 10198668
TI - The shape of our river.
PMID- 10198669
TI - Prevention research centers. The academic and community partnership.
PMID- 10198670
TI - Research linkages between academia and public health practice. Building a
prevention research agenda.
PMID- 10198671
TI - Research linkages between academia and public health practice.
PMID- 10198672
TI - Using case research to enhance linkages between academia and public health
practice.
PMID- 10198673
TI - Bridging the gap between academia and practice in public health.
PMID- 10198674
TI - Applied prevention research. Challenges of working with urban communities.
PMID- 10198675
TI - Community/practice/academic partnerships in public health.
PMID- 10198676
TI - It's about time. The medicine/public health initiative.
PMID- 10198677
TI - Risk factors for excess mortality in Harlem. Findings from the Harlem Household
Survey.
AB - INTRODUCTION: In 1980, age-adjusted mortality rates in Central Harlem were the
highest among New York City's 30 health districts. This population-based study
was designed to describe the self-reported frequency of selected health
conditions, behavioral risk factors, preventive health practices, and drug use in
the Harlem community. METHODS: From 1992 to 1994, in-person interviews were
conducted among 695 adults aged 18 to 65 years who were randomly selected from
dwelling-unit enumeration lists for the Central Harlem health district.
Descriptive statistics were computed for men and women separately, and compared
to other population-based surveys. RESULTS: Self-reported medical insurance
coverage in Harlem was unexpectedly high (74% of men, 86% of women) as was
lifetime use of preventive health practices, e.g., blood cholesterol screening
(58% of men, 70% of women). However, lifetime rates of substance use, e.g. crack
cocaine (14%) and self-reported history of traumatic events, e.g., witnessing
someone seriously injured or violently killed (49% of men, 21% of women) were
also high in Harlem, especially in comparison to other populations. CONCLUSIONS:
This study has identified important patterns of similarities and differences in
risk behaviors between Harlem and other populations. Potential solutions to the
health problems of Harlem may lie in the creation of strategies that operate at
the community, municipal, and regional level, as well as at the level of
individual behavior and risk-taking.
PMID- 10198678
TI - A collaborative partnership to enhance school-based tobacco control policies in
West Virginia. Center for Disease Control and Prevention.
AB - INTRODUCTION: The Centers for Disease Control and Prevention's Guidelines for
School Health Programs to Prevent Tobacco Use and Addiction were developed, in
part, to help state and local education agencies implement effective school-based
tobacco control programs. This paper: (1) reports on school tobacco policies, one
facet of a larger investigation conducted to examine the consistency between WV's
school-based tobacco control policies and programs and the CDC Tobacco Guidelines
and (2) describes the impact this investigation had on state policy in WV.
METHODS: A content analysis was conducted on all (n = 55) county tobacco policies
using a coding protocol developed by the authors. This protocol was designed to
enable judgment about whether the county policies addressed particular elements
specified in the CDC Tobacco Guidelines. Additionally, data about school-level
policies, collected from a telephone survey of a sample of school principals (n =
421), are presented. Since the purpose of the needs assessment was to describe
current practice, frequencies were computed for both the county and school-level
analyses. RESULTS: Both county- and school-level tobacco policies were found
lacking in many of the elements recommended in CDC's Tobacco Guidelines,
particularly in the areas of enforcement procedures and access to cessation
programs. CONCLUSIONS: Two major outcomes resulted from this needs assessment:
(1) the WV State Board of Education's Tobacco Control Policy was revised to be
more consistent with CDC's Tobacco Guidelines and (2) increased attention is now
being focused on providing cessation options for WV schools.
PMID- 10198679
TI - Evaluation of ENCOREplus. A community-based breast and cervical cancer screening
program.
AB - BACKGROUND: Minority women and women with low income levels are significantly
less likely to practice appropriate mammography and Pap test screening.
ENCOREplus is a health promotion program that provides outreach, education,
referral, and other service that facilitate breast and cervical cancer screening
for medically underserved women. The program is delivered through a network of
community-based nonprofit organizations (YWCA of the U.S.A). The purpose of this
study was to assess the effectiveness of ENCOREplus in promoting mammography and
Pap test screening among women who were nonadherent to screening guidelines.
METHODS: Baseline data were collected from women participating in the program.
Follow-up occurred within six months of baseline to assess whether or not
enrollees received recommended screenings. Screening-completion rates were
compared to rates from other published intervention studies. RESULTS: Data from
the program's second implementation year show that 27,494 women participated in
the ENCOREplus program. Over half the women were racial/ethnic minorities, over
75% reported annual incomes under $15,000, and 49% reported no insurance. Among
women 40 and over, 69.7% were nonadherent to ACS mammography screening guidelines
at baseline. Among participants 18 and older, 68.9% were nonadherent to Pap test
screening guidelines. Of nonadherent participants, 57.8% received mammograms and
36.5% received Pap tests. Both mammography and Pap test screening-completion
rates compared favorably with other programs. CONCLUSION: This study demonstrates
that programs implemented through community-based organizations can be successful
in increasing mammography and Pap test screening among low-income and minority
women.
PMID- 10198680
TI - Evaluation of a community-based program to improve infant immunization rates in
rural Minnesota.
AB - OBJECTIVE: The purpose of this study was to evaluate the effects of enrollment in
a community-based public health nursing program, Communities Caring for Children
(CCC), on infant immunization rates in rural Minnesota. The program involved
health education, a registry, and a reminder system. DESIGN: The evaluation was a
collaborative effort of university, public health agency, and private managed
care personnel. Two data sources were used to assess the association of program
enrollment and immunization compliance; public birth certificates and a telephone
survey of 421 CCC enrollees and non-enrollees. RESULTS: Birth certificate and
survey data showed that CCC enrollees were significantly younger, less educated,
more likely to be white, and of lower parity than non-enrollees. The average age
of subjects' infants was eight months. The survey data showed that, overall, CCC
enrollees perceived less danger in infant immunizations than did non-enrollees
and were more likely than non-enrollees to have access to infant immunization
reminder cards. CCC enrollees reported significantly higher immunization
compliance for their infants than did non-enrollees. CONCLUSIONS: The area served
by this program is relatively low-income and rural. Infant immunization status
was among the lowest in Minnesota prior to the implementation of CCC. The
evaluation suggested that enrollment in CCC was one of the most powerful
predictors of infant immunization compliance.
PMID- 10198681
TI - Cancer prevention in rural primary care. An academic-practice partnership.
AB - BACKGROUND: Cancer screening rates are particularly low among poor, minority, and
rural women, those segments of the population with the highest cancer mortality
risk. Therefore, targeted strategies to increase screening in these population
groups are needed. METHODS: This paper describes a partnership between the
University of Alabama at Birmingham (UAB) and Family HealthCare of Alabama, a
nonprofit health care agency, initiated to promote cancer control and prevention
in a predominantly low-income, African-American population in rural western
Alabama. The partnership has collaborated in the development of two research
proposals designed specifically to evaluate cancer control strategies within the
context of routine health care delivery. RESULTS: The UAB/Family HealthCare
partnership is conducting two randomized treatment outcome studies funded by the
National Cancer Institute to evaluate theory-based patient management strategies
to promote patient adherence to screening recommendations for cervical cancer and
breast cancer. CONCLUSIONS: The success of this academic-practice partnership can
be seen in the funded research projects, the enhancement of preventive services
in rural primary care, and in the potential to disseminate theory-based cancer
control strategies throughout an extended primary care network.
PMID- 10198682
TI - The Missouri Disability Epidemiology and Health Project.
AB - INTRODUCTION: Estimates of disability in this country are as high as 20%. State
health departments need to provide the core activities to deal with this public
health problem including assessment, policy development, and assurance. A
collaboration among academic institutions and the Missouri Department of Health
(MDOH) is a model for providing this core. METHODS: A disability workgroup was
established among bureaus of the MDOH and three universities. This group selected
the disability domain of mobility impairments for initial work. Existing data
from the Centers for Disease Control and Prevention's (CDC) Behavioral Risk
Factor Surveillance System (BRFSS) in Missouri and data from the 1990 Census were
analyzed. Dissemination of the findings involved community and consumer
participation via an advisory group and a public health-sponsored conference on
disability. In addition, new data collection efforts are underway using the
BRFSS. Education and training activities include both public health students and
public health practitioners in learning the content and methodology associated
with disability epidemiology. RESULTS: Data analyses have identified rural
geographic areas of the State with high levels of disability and a trend of
increasing work disability since 1993. A selected key condition, arthritis, has
been confirmed as having a high prevalence (28%) in Missouri. These data also
demonstrate that there is a strong risk of limitations associated with arthritis
[adjusted odds ratio (OR) 3.57; 95% confidence intervals 3.0, 4.2]. These results
will be applied to program planning. CONCLUSIONS: The Missouri program is
succeeding in providing both academic and public health practice partners with a
productive experience that meets the needs of each.
PMID- 10198683
TI - Measuring the impact of prevention research on public health practice.
AB - CONTEXT: Prevention research involves the translation of established and
promising methods of disease prevention and health promotion to communities.
Despite its importance, relatively little attention has been paid to systematic
approaches to determining the impact of prevention research on public health
practice. Evaluation of these effects is challenging, particularly in light of
multi-factor causation, long time periods between exposure and disease
occurrence, and difficulties in determining costs and benefits. OBJECTIVE: To
develop a framework that allows the prospective or retrospective evaluation of
the effects and effectiveness of prevention research. RESULTS: The proposed
framework allows assessment of prevention research in five areas of public health
practice: surveillance and disease investigation, program delivery, policies and
regulations, recommendations to the public, and public health education and
training. A brief case study of environmental tobacco smoke illustrates the
public health impact of prevention research. CONCLUSIONS: Greater translation of
prevention research findings is needed to accomplish public health goals--efforts
are enhanced by academic-practice partnerships. The relevance and utility of the
current framework needs additional testing with a variety of public health
issues.
PMID- 10198684
TI - Creating training opportunities for public health practitioners.
AB - In response to several reports issued by the federal government and private
foundations on the under-training of public health practitioners, Joseph L.
Mailman School of Public Health of Columbia University (SPH) and the New York
City Department of Health (NYC DOH) initiated the Public Health Scholars program
(SPH-PHS) to make degree-level public health training available to NYC DOH
employees. Public Health Scholars receive a 50% tuition scholarship and enroll
part-time while working full-time at NYC DOH. Sixteen scholars have enrolled
during the past three years. The SPH-PHS program is considered a success by both
SPH and NYC DOH. This article details the history of the collaboration between
the two agencies and the structure of the program and provides a critical
analysis of the SPH-PHS program based on interviews with 16 scholars. It also
examines the cost and benefit to other schools of public health of implementing
such a program.
PMID- 10198685
TI - Principles of practice for academic/practice/community research partnerships.
AB - CONTEXT: Researchers and practitioners are increasingly realizing that
improvements in public health require changes in individual, social, and economic
factors. Concurrent with this renewed awareness there has been a growing interest
in working with communities to create healthful changes through
academic/practice/community research partnerships. However, this type of research
presents different challenges and requires different skills than traditional
research projects. The development of a set of principles of practice for these
types of research projects can assist researchers in developing, implementing,
and evaluating their partnerships and their project activities. OBJECTIVE: This
paper describes the different ways in which academics and community groups may
work together, including academic/practice/community partnerships. Several
principles of practice for engaging in these research partnerships are presented
followed by a description of how these principles have been put into operation in
a family violence prevention program. CONCLUSIONS: The principles presented are:
(1) identify the best processes/model to be used based on the nature of the issue
and the intended outcome; (2) acknowledge the difference between community input
and active community involvement; (3) develop relationships based on mutual trust
and respect; (4) acknowledge and honor different partner's "agendas"; (5)
consider multi-disciplinary approaches; (6) use evaluation strategies that are
consistent with the overall approach taken in the academic/practice/community
partnership; and (7) be aware of partnership maturation and associated transition
periods. The limitations of these principles and their application in various
settings are discussed.
PMID- 10198686
TI - Public/private partners. Key factors in creating a strategic alliance for
community health.
AB - BACKGROUND: The rapidly evolving American health system creates economic and
societal incentives for public and private health organizations to collaborate.
Despite the apparent benefits of collaboration, there is a paucity of information
available to help local agencies develop partnerships. This study, itself a
collaboration between a school of public health (SPH) and a Georgia health
district, was undertaken to identify critical factors necessary to successfully
initiate and sustain a public/private community health collaboration. METHODS:
Professional staff at the SPH conducted 26 standardized interviews involving
participants from Cobb and Douglas counties Boards of Health; Promina Northwest
(now known as Wellstar), a not-for-profit health system; and community
stakeholders. Content analysis of each interview question was performed and
comparisons were made both within each group and across groups. RESULTS: Trends
were identified in the following key areas: vision of health care for Cobb and
Douglas counties, forces driving collaboration, strengths of each organization,
critical negotiating issues, and potential community gain resulting from the
partnership. CONCLUSION: A shared vision between potential collaborators
facilitates communication regarding strategies to achieve common goals. A
previous history of working together in limited capacities allowed the partners
to develop trust and respect for one another prior to entering negotiations.
These factors, when taken in conjunction with each organization's strong
leadership and knowledge of the community, build a strong foundation for a
successful partnership.
PMID- 10198687
TI - Positioning for partnerships. Assessing public health agency readiness.
AB - BACKGROUND: Public health organizations are redefining their roles and aligning
their structures with other components of the evolving American health system.
Health departments must proactively and strategically plan how to position
themselves for the coming years. Prior to implementing changes in functioning,
structure, and/or future strategies, an organization should assess its internal
readiness to commit to creating these substantial alterations. METHODS: Using a
diagnostic tool developed by study investigators, employees of the Cobb and
Douglas Counties Boards of Health were surveyed in order to assess their
organizational readiness to enter into a strategic partnership with Promina
Northwest, a not-for-profit hospital network in the Atlanta, Georgia area.
Frequency distributions were conducted for each categorical variable and data
were analyzed in aggregate and by job category. RESULTS: The 122 analyzed
questionnaires revealed some significant trends. Respondents ranked the six
factors having the greatest impact on an organization's ability to change in the
following order: leadership, planning, teamwork, mission, information and
operations. Interestingly, this rank ordering parallels the perceived strengths
and weaknesses of the health departments as determined by the frequency of the
most positive responses. CONCLUSION: Cobb and Douglas Counties Boards of Health
have taken many key steps to prepare the organizations for significant proactive
changes. Survey results emphasized the need for open channels of communication
within the organizations and with the external environment so that effective
planning can guide the strategic alignment of the health departments with
community partners.
PMID- 10198688
TI - "McFlu". The Monroe County, New York, Medicare vaccine demonstration.
AB - BACKGROUND: Monroe County (MC) NY was one of 9 original sites for the 1988-1992
Medicare Influenza Vaccine Demonstration, which led to Medicare coverage of
annual influenza vaccination. The "McFlu" project involved collaboration among
university, health department, and practice community. METHODS: Community-wide
systems for promoting and/or documenting influenza vaccine delivery and for
conducting laboratory-based influenza surveillance were established in MC and in
neighboring Onondaga County (OC), which served as a comparison site without
Medicare coverage of vaccination. Vaccination utilization and virologic
surveillance data collected from physician practices, hospitals, and nursing
homes were furnished to national demonstration evaluators. RESULTS: Influenza
vaccination rates among persons > or = 65 years of age increased from 41% to 74%
in MC compared to an increase from 46% to 57% in OC. The greatest increase
occurred in physician offices utilizing an innovative vaccination promotion and
tracking strategy. Community-wide influenza A/H3N2 and B outbreaks were
documented in three successive demonstration years, affording investigators the
opportunity to better define influenza impact and vaccine effectiveness among the
Medicare population. CONCLUSION: The McFlu project exemplifies the potential for
linking the academic and public health sectors to complement each others'
strengths in planning, implementing and documenting a targeted program for
improving community health. This model of medicine and public health
collaboration should be applicable to attaining other well articulated goals for
the health of the public.
PMID- 10198689
TI - Assurance opportunities for local health departments.
AB - CONTEXT: Widespread changes in health care in the United States, especially the
growth in the number and membership of health maintenance organizations (HMOs),
provide increasing opportunities for collaboration, especially through contracts,
between local health departments (LHDs) and HMOs to achieve public health goals.
OBJECTIVES: (1) To identify, through a review of the literature, the areas in
which HMOs and LHDs can collaborate to their mutual benefit and (2) for the
leadership of an LHD in Florida to engage HMOs in its county in Florida in
collaboration. DESIGN: University faculty reviewed the relevant literature; the
Director of Medical Services for the Duval County Health Department developed the
relationships with Duval County HMOs. SETTING: The setting for the study was
Duval County. PARTICIPANTS: The participants in the study included faculty from
the College of Public Health at the University of South Florida, State and county
public health officials, and representatives of 10 HMOs. MAIN OUTCOME MEASURES:
The main outcome measures were a literature review to identify feasible areas for
collaboration and successful collaboration with HMOs in areas of mutual interest.
RESULTS: The director of medical services for the county health department
initiated a variety of collaborative activities with 10 HMOs. These led to
agreements, participation on committees and task forces, provision of services,
and improved communication. CONCLUSIONS: Collaboration between LHDs and HMOs to
achieve public health assurance goals is feasible. Other organizations can
encourage such collaboration through public and private policies.
PMID- 10198690
TI - [Fatal incidences during arrest of highly agitated persons].
AB - We report on four cases of sudden circulatory arrest during the physical
restraint of extremely excited and repugnant men by the police. Three persons
died, and one became apallic. The excited states resulted from acute
schizophrenic disorder in one case, from intoxications (ethanol and drugs
including cocaine respectively) in two others, and from encephalitis in the
fourth case. In only one case one of the police officers was condemned for
involuntary mansloughter, responsability was excluded in the remainder. Similar
lethal events in "excited delirium" are given in the American literature, the
main etiologic factors being acute psychosis and cocaine intoxication. Most of
these events occurred, differing from ours, under "hogtying" which is a technique
of physical restraint in a prone position with the wrists and ankles bound behind
the back. These events are thought to be cardiac in origin and to result from
oxygen-consuming motor hyperactivity, excessive catecholamine release, and
impaired breathing. Police officers are recommended to restrict all measures of
restraint to a mininum in extremely excited persons, and to avoid any compression
of the trunk or neck. A continuous monitoring for vital signs is postulated in
order to recognize a medical incident as quick as possible.
PMID- 10198691
TI - [Pump-gun as a weapon. Type of injuries, prohibition of weapons].
AB - Pumpguns are shotguns with pump action whose injuries and wound mechanisms have
several special features: extremely high kinetic energy of the shot (2500 to 3500
J) frequent cases of "Kronlein shots" (exenteration of the brain)
punchmark/imprint immediately adjacent to the entrance wound from the front of
the pipe magazine exit wounds from buckshot may be similar to pellet entrance
injuries from a distant shotgun discharge the use of various shotgun cartridges
(plastic ammunition, slug bullet, various lead pellets) within the same weapon.
The change in the Austrian gun law and the banning of the pumpgun in 1995 is also
discussed in the article.
PMID- 10198693
TI - [Fatal propane-butane poisoning].
AB - Two lethal poisonings by butane and propane are described, and the corresponding
concentrations in the body fluids and organ tissues are evaluated. One case
appeared to be an accident after deliberate inhalation for butane, one was a
suicide. The mechanism of the inhalation could be reconstructed in both cases.
The concentrations in the biological material agreed well with observations in
similar cases.
PMID- 10198692
TI - [Self-injury or attempted murder--analysis of an unusual case].
AB - An unusual case of self-injury involving several, partly deep penetrating stab
wounds is described. A young emotionally disturbed consulting-room assistant
accused her husband of having inflicted the injuries upon her in the course of an
argument over custody of the children. An analysis of the injury pattern showed
clear indications of self-injury and willfully transferred blood from punctures
in the woman's fingertips to the clothes of the accused. The case demonstrates
that in cases involving members of a medical profession and individuals with
psychiatric disorders, the possibility of highly unusual types of self-injury
should not be excluded. It further emphasizes the importance of a physical
examination performed by a medico-legal specialist.
PMID- 10198694
TI - [Comparison of wound morphology following gunshots by machine guns and sub
machine guns].
AB - Automatic weapons such as machine guns and submachine guns are found in the
German-speaking region only in special army and police units and appear
accordingly rarely in homicides, suicides and accidents. In the following, the
findings in two cases of death with the use of machine and submachine guns are
presented. The first case was a fatal accident during shooting on a training area
(current machine gun of the German army, calibre 7.62 x 51 mm), the second case
was a killing during a physical conflict (submachine gun MP 40 from World War II,
calibre 9 x 19 mm). In the case with the machine gun autopsy disclosed typical
entry holes corresponding to the calibre, but unusually large exit wounds with
tissue bridges in the wound ground, measuring 4 x 2.5 cm in diameter. By
contrast, the second case (submachine gun) showed "normal" entry and exit wounds.
The differences are mainly caused by deviating ballistic data of the ammunition
used. They are discussed against the background of literature on wound
ballistics.
PMID- 10198695
TI - [Techno-festival mit fatal outcome].
AB - The authors report on a 21-year old female who died suddenly during a techno
festival. The autopsy findings and the results of chemical-toxicological analyses
were not able to clear up the cause of death. Pathophysiological and
toxicological considerations demonstrate that only a combination of facts are
sufficient to explain the sudden death of this young woman.
PMID- 10198696
TI - [Evidence of DNA from epithelial cells of the hand of the suspect found on the
tool of the crime].
AB - A young woman was found unconscious in her flat strangulated with a children's
scarf and was at first thought to be dead. The victim survived but is disabled
for life. Neither bloodstaines nor sperm were found at the scene. Swebs of fleece
were prepared from two fingers of a one-way glove which were found at the scene
and from each end of the scarf in order to find some epithelial cells from the
criminal. DNA was extracted and amplified by the polymerase-chain-reaction (PCR).
The DNA-profile of the victim as well as that of the suspected apart living
husband were found in these mixed stains. The suspect was severely incriminated
by these findings and other evidence. Consequently the court convicted him to
eleven years of inprisonment because of attempted manslaughter.
PMID- 10198697
TI - [A.V. Smol'iannikov and the development of the Pathology Service in Russia].
PMID- 10198698
TI - [New approaches to antitumor therapy of various morphological variants of primary
bone sarcoma].
AB - The data of foreign literature and original findings on possible role of auto-,
paracrine and endocrine mechanisms of bone sarcoma growth regulation are reviewed
basing on observation in these tumors of receptors of the epidermal growth factor
(REGF), EGF-like peptides, receptors of glucocorticoids, androgens and estrogens.
Link of these indices with clinicomorphological characteristics of the disease
and its prognosis is suggested. REGF in primary bone tumors may serve as targets
for therapy with drugs influencing EGF-dependent mechanism of tumor growth
stimulation. Groups of these drugs are considered in detail.
PMID- 10198699
TI - [Role of Epstein-Barr virus in the pathogenesis of lymphogranulomatosis.
Immunohistochemical and molecular-biological (hybridization in situ) research].
AB - EBV was found in 72.7% of 66 LGM patients aged from 4 to 76 years. EBV occurred
in 100% of lymphoid depletion, 81% of mixed-cell variant and in 66.6% of nodular
sclerosis. The occurrence of virus-positive cases was significantly higher at the
age of under 10 years and over 50 years (100%). In the intermediate group it was
65.4 (p < 0.01). Necrotic changes in the lymph nodes were observed more
frequently (p < 0.05) when EBV was present. The virus-positive cases of mixed
cell LGM are characterized by increased number of tumor and plasma cells (p <
0.05). EBV was also in a latent state without signs of lytic replication. The
influence of the virus manifested in higher expression of antigens CD30 (p <
0.05) and bcl oncoproteins (p < 0.01) as well as in weak CD79 expression (p <
0.05).
PMID- 10198700
TI - [Morphologic and molecular-genetic characterization of lung cancer developing in
people who have worked at nuclear facilities and who have lived in Russian
territories polluted after the accident at the Chernobyl power plant].
AB - Clinicomorphological analysis of 15 lung carcinomas of patients who had been
exposed for a long time to the radiation after the Chernobyl accident was
performed. The material consisted of 10 surgical and 5 autopsy cases and was
studied at the light, electron microscopic and immunohistochemical level. There
were 6 peripheral, 8 central carcinomas and one massive tumor. Fibrous areas with
many dust particles were found in peripheral carcinomas. In central tumors
chronic obstructive bronchitis with epithelial dysplasia and metaplasia was
observed. Carcinoma was represented by various histologic types: small cell (4
cases), combined small cell with squamous differentiation (5 cases),
adenocarcinoma (5 cases), adenosquamous type (1 case). Peculiar calcium deposits
in both stroma and parenchyma were found in tumors with glandular
differentiation. Morphogenesis of calcium microdeposits may be connected with
dust radioactive particles elimination. Central carcinoma had, in the majority of
cases, a neuroendocrine differentiation and can be related to some types of small
cell carcinoma. Peripheral cancer was mostly of a glandular differentiation and
was, as a rule, carcinoma in the scar. Lung carcinomas studied had peculiar
molecular-genetic features: lack or low bcl-2 expression, low Ki-67 expression
and a high degree of c-myc expression. Tumors were characterized by a low
apoptosis index independently of a histologic type. Apoptosis was not complete:
lack of apoptotic bodies phagocytosis this resulting in postapoptotic detritus
formation.
PMID- 10198701
TI - [Reactive restructuring of smooth muscle tissue in response to large fraction
irradiation of rectal cancer].
AB - Rectum smooth muscles of 19 patients were studied after presurgical irradiation.
A comparative analysis of isolated smooth myocytes from various areas of resected
intestine was performed morphometrically and cytophotometrically. Suppression of
proliferative activity and protein synthesis, elimination of large myocytes were
observed in the foci of intensive irradiation. Smooth myocytes in the margin
zones retain structure, proliferative potential and cytoplasmatic protein content
this allowing to consider smooth muscles of these zones to be able for complete
reparative regeneration. Electron microscopy confirmed the structural alteration
observed.
PMID- 10198702
TI - [Racemose arteriovenous angioma (malformation) of the brain].
AB - 242 cases of brain arterio-venous malformations (AVM) are analysed clinically and
anatomically. Their pathology, histological, ultrastructural and
immunohistochemical characteristics, therapeutic pathomorphosis are described.
The concept is suggested according to which AVM is a collective term including
true developmental defects, dysembryogenetic tumors and outcomes of various
pathologic processes (trauma, brain circulation and compensatory-adaptive
disturbances, etc.). The necessity of therapeutic methods corrections in
agreement with the disease pathogenesis is outlined.
PMID- 10198703
TI - [Liver changes in people of conscription age--"carriers" of hepatitis B and C
viruses].
AB - 89 liver needle biopsies from young persons--HBV and HCV carriers--were studied
histologically, immunohistochemically, morphometrically and electron
microscopically. Groups with compensatory-adaptive and degenerative liver
lesions, those with mild manifestations of a chronic virus infection, and those
with chronic hepatitis of minimal and weak activity were identified. Latent
chronic hepatitis is found in 68.5% of HBV and HCV carriers. Morphological
picture of HCV infection is more pronounced as compared to that of HBV infection.
The role of eosinophils in the development of hepatitis B and C forms lacking
clinical symptoms is demonstrated.
PMID- 10198704
TI - [Expression of NADPH-diaphorase in the peripheral nerve and its changes at
different stages of diphtheritic polyneuropathy].
AB - Distribution and intensity of NADPH-d reactivity, a marker for enzyme of the
nitric oxide synthesis, in nervus suralis biopsies in severe DP were studied at
light and electron microscopic levels. The study of control specimens has shown
that NADPH-d reactivity was permanently present in Schwann cells (SC) and was
distributed in all parts of their cytoplasm. Axon and myelin were devoid of NADPH
d reactivity. A decrease of enzyme reactivity in SC cytoplasm of the damaged
nerve fibers and rising enzyme reactivity in the cytoplasm of activated SC were
observed in DP. High reactivity in SC of small fibers was found at earlier stages
and that of thick fibers at later stages. This distinction reflected, apparently,
sequence of entering at first thin, then thick fibres in the reparative process.
Under the electron microscope, the reaction product was deposited on membranes of
endoplasmic reticulum, nuclear membrane and Golgi complex. The enzyme was also
located in nucleus of activated SC. Ultrastructural location and the fact that
the highest intensity of reaction is present in SC of nervous fibres with
morphological signs of remyelination suggest link of this enzyme with the
reparative process. This study provides the first evidence of NADPH-d reactivity
in SC and shows that NADPH-d histochemistry is a useful tool for peripheral nerve
biopsies study.
PMID- 10198705
TI - [Rupture of an atherosclerotic aneurysm of the common iliac artery].
AB - A complex symptom complex developed in a 76-year-old man with atherosclerotic
right artery ililaca communis aneurysm and was caused by retroperitoneal rupture.
It was characterized by incomplete small intestinal ileus, progressive
hydronephrosis, ischemia and chronic venous insufficiency of the right leg.
PMID- 10198706
TI - [The Pathology Service today].
PMID- 10198707
TI - [A device for demonstrating micropreparations "histoskop"].
AB - A device "Histoscop" for demonstration of histologic preparations is described.
The device has a powerful lighting system enabling it to reflect images of
histological structures from the microscope objective to a screen. The device is
multipurpose (can be used in conferences, teaching, etc.).
PMID- 10198708
TI - [Does alcoholic chronic hepatitis exist?].
AB - Alcoholic chronic hepatitis (ACH) can be considered as an independent nosological
entity. This conclusion can be made basing on the literature devoted to the
mechanisms of ethanol effects on the liver and clinicomorphological features of
hepatic ethanol damage. ACH should be included into the new 1994 International
classification of chronic hepatitis. Special attention is paid to a higher
incidence of combined liver damage induced by alcohol and hepatotropic viruses,
especially by hepatitis C virus. Combined virus-alcoholic liver damage will
become, in the author's opinion, one of the most important hepatology problems in
the coming millenium.
PMID- 10198710
TI - [Attempt to assimilate the initial basis of medicine and autopsy practice under
conditions of the Ukhto-iznem camp for political prisoners].
AB - The author recalls heavy labor and work in hospitals of the Ukhto-Izhem
penitentiary for political prisoners where he spent 8 years (1938-1946) including
5 years as a prisoner. Being in the past a student of an industrial technical
school, in the penitentiary he worked as a medical assistant, doctor,
pathologist. His first research was dermal lesions in pellagra. The prisoners who
worked as assistants and physicians contributed much to improving diagnosis and
treatment in the penitentiary. The author in the future received medical
education and worked as a pathologist and eventually became a professor.
PMID- 10198711
TI - [The first All-Russian workshop on immunohistochemical diagnosis of tumors].
PMID- 10198712
TI - Present status of the total artificial heart at the University of Tokyo.
AB - At the University of Tokyo, various types of total artificial heart (TAH) systems
have been studied since 1959. At the present time, 2 types of implantable TAH
have been developed. One is an undulation pump TAH (UPTAH) and the other is a
flow transformed pulsatile TAH (FTPTAH). Using the UPTAH, 14 cases of
implantation were performed in goats and 10 days' survival obtained. The new type
of FTPTAH is under a prototype study. To prevent ring thrombus, a polyurethane
membrane valve, a jellyfish valve, has been developed. The longest in vivo
experiences with this valve in the TAH blood pump have been 312 days in the left
side blood pump and 414 days in the right side blood pump. Conductance and
arterial pressure based control (1/R control) can realize the physiological
control of the TAH. Using 1/R control, 532 days of survival could be obtained in
a goat with a paracorporeal TAH. The technique required to apply this control
method to a implantable TAH is under development. We have proposed a new 5 year
research project of the implantable TAH entitled "Comprehensive Basic Research on
the Development of a Japanese Original Implantable Total Artificial Heart" to The
Ministry of Welfare.
PMID- 10198713
TI - Three-dimensional thoracic modeling for an anatomical compatibility study of the
implantable total artificial heart.
AB - Anatomical compatibility with the thoracic cavity is important in developing a
completely implantable total artificial heart (TAH). The purpose of this study
was to examine the optimal morphology of our TAH and to develop a computer
implantation simulation environment for preoperational discussion. As the first
stage, we constructed a prototype simulation system by creating a 3-D surface
model of a thoracic cavity and one of a TAH. In this system, the thoracic surface
model, composed of the aorta, pulmonary artery, ventricle resected heart,
diaphragm, and thoracic wall, was created based on the organ contours extracted
from electrocardiogram (ECG)-synchronized ultrafast computer tomographic images.
The accuracy of the thoracic model was discussed using a phantom. The fitting
study can be performed on the computer with the model of the thorax and that of
the TAH. In the future, construction of a database for the thoracic cavities of
heart failure patients is planned to improve the morphology of the TAH.
PMID- 10198714
TI - The development of a control method for a total artificial heart using mixed
venous oxygen saturation.
AB - For physiological control of a total artificial heart (TAH), applying mixed
venous oxygen saturation (SVO2) as a parameter for TAH control is a promising
approach regarding sensitivity to the recipient's oxygen demand and the practical
possibility of continuous monitoring using near infrared rays through transparent
blood pump housings. To develop a control method for the TAH using SVO2, the
relationship between SVO2 and cardiac output (CO) was investigated in a normal
calf, and a control algorithm was developed based on this correlation. Then the
feasibility of this method (SVO2 mode) was evaluated in a calf implanted with a
pneumatic TAH and compared with the fixed drive control mode (fixed mode) in
which the drive parameters were unchanged. The calf performed a graded exercise
test in both modes. The CO was effectively increased from 7.3 to 13.0 L/min in
the SVO2 mode, and the capacity for exercise was augmented compared to the fixed
mode. We conclude that this SVO2 mode is feasible and may be effectively applied
in TAH control.
PMID- 10198715
TI - In vivo evaluation of the national cardiovascular center electrohydraulic total
artificial heart.
AB - We have been developing an electrohydraulic total artificial heart system. The
system comprises an intrathoracic pumping unit composed of diaphragm type
ellipsoidal blood pumps and an energy converter in addition to an electronics
unit. The in vivo performance of the pumping unit was evaluated in a series of
animal implantations with 3 calves weighing 62-85 kg. An interatrial shunt 4.5 mm
in diameter was made in the atrial septum to compensate left-right imbalance. Two
calves died early postoperatively, one of external controller power failure and
the other of interatrial shunt stenosis due to thrombus formation. One calf,
however, survived over 10 days under stable circulatory conditions. No
abnormality was found in the oxygen metabolic condition or in major organ
functions. The generation and dissipation of heat from the device was acceptable.
This animal died of device malfunction caused by energy converter bearing
breakdown. The device demonstrated a good anatomic fit without compromising the
great vessels and adjacent tissues. It is concluded that the pumping unit has a
sufficient in vivo basic performance although appropriate countermeasures are to
be implemented against the detected problems concerning mechanical durability and
interatrial shunt patency.
PMID- 10198716
TI - Evaluation of an implantable motor-driven left ventricular assist device.
AB - A console based implantable motor-driven left ventricular assist device (LVAD)
was developed and tested. Ten sheep weighing 42-73 kg (mean, 54.4 kg) were used
as the experimental animals. Four animals survived 5-12 h (mean, 9.5 h). The mean
pump flow was 1.63 L/min, ranging from 0.8 to 2.5 L/min. The cause of termination
was respiratory failure in 3 animals, bleeding in 2, ventricular fibrillation in
2, vent tube obstruction in 1, thrombus formation in 1, and mechanical failure of
the driving console in 1. Following the in vivo studies, the computer regulated
controller was tested in a mock circulatory system. The LVAD provided 5.34 L/min
of maximum output against a mean afterload of 80 mm Hg with a filling pressure of
15 mm Hg when the pump rate was 80 bpm in the fixed rate mode. With an increase
in the pump afterload from 80 to 140 mm Hg, the total system efficiency varied
from 7.81 to 8.34% when the pump preload was 15 mm Hg. An ultracompact,
completely implantable electromechanical VAD has been under development. This
device should fit in a 60 kg adult. As the next step, we are preparing to implant
this ultracompact implantable VAD with an electronic controller in an animal
model with better results being expected.
PMID- 10198717
TI - Ultracompact, completely implantable permanent use electromechanical ventricular
assist device and total artificial heart.
AB - An ultracompact, completely implantable permanent use electromechanical
ventricular assist device (VAD) and total artificial heart (TAH) intended for 50
60 kg size patients have been developed. The TAH and VAD share a miniature
electromechanical actuator that comprises a DC brushless motor and a planetary
roller screw. The rotational force of the motor is converted into the rectilinear
force of the roller screw to actuate the blood pump. The TAH is a one piece
design with left and right pusher plate type blood pumps sandwiching an
electromechanical actuator. The VAD is one half of the TAH with the same actuator
but a different pump housing and a backplate. The blood contacting surfaces,
including those of the flexing diaphragm and pump housing, of both the VAD and
TAH were made of biocompatible polyurethane. The diameter, thickness, volume, and
weight of the VAD are 90 mm, 56 mm, 285 cc, and 380 g, respectively, while those
of the TAH are 90 mm, 73 mm, 400 cc, and 440 g, respectively. The design stroke
volume of both the VAD and TAH is 60 cc with the stroke length being 12 mm. The
stroke length and motor speed are controlled solely based on the commutation
signals of the motor. An in vitro study revealed that a maximum pump flow of 7.5
L/min can be obtained with a pump rate of 140 bpm against a mean afterload of 100
mm Hg. The power requirement ranged from 4 to 6 W to deliver a 4-5 L/min flow
against a 100 mm Hg afterload with the electrical-to-hydraulic efficiency being
19-20%. Our VAD and TAH are the smallest of the currently available devices and
suitable for bridge to transplant application as well as for permanent
circulatory support of 50-60 kg size patients.
PMID- 10198718
TI - Ex vivo evaluation of a roller screw linear muscle actuator for an implantable
ventricular assist device using trained and untrained latissimus dorsi muscles.
AB - In this study, the power output and contraction length of trained and untrained
canine latissimus dorsi (LD) muscles were measured using a roller screw linear
muscle actuator (RSLMA). The RSLMA consisted of a roller screw-nut assembly and
translation unit to convert the linear pull force of the muscle into an axial
displacement of the roller screw. When a cable wound around a spool attached at
each end of the roller screw nut was pulled in either direction, the nut was
rotated which in turn advanced the roller screw in the axial direction. Under
anesthesia, a Telectronics myostimulator (Model 7220) was implanted in the
subcutaneous area of the canine left thoracic region with its bipolar
intramuscular leads implanted around the thoracodorsal nerve and the distal
muscle. A total of 6 dogs went through the myostimulator implantation, followed
with 8 weeks of continuous stimulation. After completion of the training, the
contraction lengths of the trained and untrained LD muscles were measured, and
they were 4.25 and 5.5 cm, respectively, while the instantaneous power outputs
were 4.24 and 8 W, respectively. Although untrained muscles could provide much
higher instantaneous power immediately following the start of the stimulation, it
diminished rapidly. On the other hand, the trained muscle showed prolonged
fatigue resistance. The thoracolumbar and humeral approaches in attaching the
actuator cable did not show a difference with respect to muscle power output. The
trained LD muscle can provide sufficient power in the range of 3-4 W to drive a
left heart assist device, but its long-term evaluation awaits development of an
appropriate muscle-device interface for chronic in vivo application.
PMID- 10198719
TI - A future prediction type artificial heart system.
AB - The demand of the biological system needs to be predicted to consider the quality
of life (QOL) of a patient with an artificial heart system. The purpose of this
study was the prediction of the imminent cardiac output and the predictive
control for an artificial heart. For that purpose, autonomic nerve information
was applied in this study. Nervous sympathicus action potentials were measured,
and a prediction function of cardiac output was made using the sympathetic tone
and preload and after-load measurement with multiple regression analysis. The
predicted value showed significant correlation with the measured value after 2.9
s. Currently, however, long-term instrumentation of the nervous sympathicus
potential is difficult. Thus, hemodynamic fluctuations, which recently have
attracted attention, were used in this study. A prediction function using the
Mayer wave, which represented nervous sympathicus, was determined. As a result,
mid-term prediction became possible. Furthermore, a measurement of the vagal
nerve was used as a possible long-term prediction parameter. For long-term
prediction, Hurst exponent analysis was used in this study. Vagal nerve
discharges in the changing position showed alteration of long-term determination.
In conclusion, the future prediction control of an artificial heart takes shape
using these prediction functions.
PMID- 10198720
TI - A preliminary study of microcapsule suspension for hemolysis evaluation of
artificial organs.
AB - A microcapsule suspension, a substitute for animal blood in hemolysis tests, has
been developed for evaluation of the absolute hemolytic properties of circulatory
artificial organs. The microcapsule suspension was made by dispersing
microcapsule slurry into an ethylene glycol sodium chloride solution. The
microcapsule slurry was composed of a leuco dye solution and polyurethane
membrane made by the reaction between aliphatic poly-isocyanate and polyamine by
interfacial polycondensation. The microcapsule was a small particle containing
dye inside. The microcapsule suspension was white; the diameter of the
microcapsules was from 5 to 100 microns. The specific gravity of the suspension
was 1.024, and the membrane was elastic. The fluid showed Newtonian
characteristics, different from animal blood, and its viscosity was approximately
5.8 mPa.s. After the microcapsules were destroyed, the leuco dye was extracted
with n-hexane from the suspension and was measured by spectroscopy after being
colored with acid ethanol. Hemolysis can be regarded as a fatigue fracture of
cell membranes rather than a static fracture. The destruction of microcapsules by
a Potter type tissue grinder was observed at a low stroke number region and was
compared to rat blood. Moreover, hemolysis tests of a commercially available
centrifugal blood pump and the prototype of our centrifugal pump for mechanism
checks were carried out with bovine blood. The hemolysis level of the prototype
pump increased with time while the hemolysis level of the commercial blood pump
did not change as much as that of the control when both pumps were tested with
the microcapsule suspension. These results are similar to tests utilizing bovine
blood. Therefore, hemolysis tests of circulatory artificial organs completed with
microcapsule suspension are expected to provide results similar to tests with
animal blood.
PMID- 10198722
TI - Clinical experience of left ventricular assist systems at the Heart Institute of
Japan.
AB - The main indications for left ventricular assist system (LVAS) support are
postcardiotomy ventricular failure as temporary circulatory support and end-stage
cardiomyopathy as chronic circulatory support. To clarify the efficacy of LVAS
support, we assessed the clinical outcome of a pneumatic LVAS and an
electromagnetic LVAS for patients with severe ventricular failure. As of March
1998, 5 patients with postcardiotomy ventricular failure had received the
pneumatic LVAS support, and 2 other patients with end-stage idiopathic
cardiomyopathy had undergone implantation of the electromagnetic LVAS. The drive
control of the LVAS was mainly counterpulsation in the diastole of the native
heart. In the 5 postcardiotomy patients, the duration of pneumatic LVAS support
ranged from 30 to 312 h (mean, 109.2). All 3 patients with more than 72 h support
were successfully weaned, and 2 of them survived. The other 2 patients with
cardiogenic shock and less than 36 h support could not be weaned from the LVAS.
In the 2 cardiomyopathy patients, 1 patient was well maintained by the
electromagnetic LVAS support and underwent successful heart transplantation 7
months later. The other patient has been chronically supported by the LVAS for 2
months and is doing well so far. These results suggest that selective application
of the pneumatic LVAS as a temporary support and the electromagnetic LVAS as a
chronic support might be appropriate for maximizing the effectiveness of LVAS
treatment for profound cardiac failure.
PMID- 10198721
TI - Major organ function under mechanical support: comparative studies of pulsatile
and nonpulsatile circulation.
AB - We examined a major organ function during 3 h biventricular assisted circulation
after acute myocardial infarction model in the pig. In left ventricular
circulation, the outflow cannula was placed in the ascending aorta and an inflow
cannula through the mitral valve in the left ventricle. A pump (pulsatile group,
Zeon Medical, Inc., Tokyo, Japan and nonpulsatile group, Nikkiso HPM-15, Nikkiso,
Inc., Tokyo, Japan) was connected to each cannula. In right ventricular
circulation, the outflow cannula was placed in the pulmonary artery and an inflow
cannula in the right ventricle. The right ventricular circulation was supported
by a nonpulsatile pump (Nikkiso HPM-15). The items measured were the regional
blood flows of the cortex and medulla in the kidney, white matter and gray mater
in brain, and liver; renal arterial flow; carotid arterial flow; portal vein
flow; common hepatic arterial flow; arterial ketone body ratio (AKBR); and
lactate/pyrubic acid (L/P). In the pulsatile group, the renal cortical blood flow
increased, and the medulla blood flow decreased. On the other hand, in the
nonpulsatile group, both regional blood flows decreased. That means that in the
pulsatile assisted group intrarenal redistribution improved rather than in the
nonpulsatile assisted group. In addition the liver regional blood flow, AKBR, and
L/P showed significant differences between the pulsatile and nonpulsatile groups.
On the other hand, the white matter and gray matter regional blood flows and
carotid arterial flow did not show significant differences between the groups.
The results of our study indicated that pulsatile circulation produced superior
circulation in the kidney and liver, and microcirculation on the cell level was
superior as well in early treatment of acute heart failure.
PMID- 10198723
TI - Proposal of a new electromechanical total artificial heart: the TAH Serpentina.
AB - A new type of energy converter for an electro-mechanical total artificial heart
(TAH) based on the principle of a unidirectional moving motor is described. Named
the TAH Serpentina, the concept consists of 2 major parts, a pendulum shaped
movable element fixed on one side using a joint bearing and a special shaped drum
cam. Pusher plates are mounted flexibly to the crossbar of the pendulum. A motor
drives the special shaped drum cam linked to the pendulum through a ball bearing.
The circular motion of the unidirectional moving brushless DC motor is
transferred into the linear motion of the pendulum to drive the pusher plates.
Using a crossbar with a variable length, the stroke of the pendulum and therefore
the displaced blood volume is alterable. To achieve a variable length, an
electric driven screw thread or a hydraulic system is possible. Comparable to the
natural heart, cardiac output would be determined by frequency and stroke volume.
PMID- 10198724
TI - The molecular genetics of X-linked lymphoproliferative (Duncan's) disease.
PMID- 10198725
TI - Tyrosine kinase inhibitors in chronic myeloid leukemia.
PMID- 10198726
TI - Postmastectomy radiotherapy--a topic for the nineties.
PMID- 10198727
TI - Preoperative chemoradiation for esophageal cancer.
PMID- 10198728
TI - What can be expected from elective regional radiotherapy?
PMID- 10198729
TI - Long-term outcome after postmastectomy radiation therapy for breast cancer
patients at high risk for local-regional recurrence.
AB - PURPOSE: Postmastectomy radiation therapy is often recommended for patients at
high risk for local-regional recurrence after mastectomy. However, long-term
outcomes after radiation therapy are not well described. PATIENTS AND METHODS:
Between 1977 and 1992, 221 patients at high risk for local-regional recurrence of
breast cancer after mastectomy were treated with radiation therapy, with or
without adjuvant systemic therapy. Patients were classified as high risk because
of T3 or T4 tumors (14%), positive lymph nodes (29%), close or positive margins
of resection (15%), or multiple risk factors (39%); 4% did not meet current
criteria for radiation therapy. The median age of patients was 51 years.
Radiation therapy consisted of 45 to 50.4 Gy to the chest wall in 1.8 to 2.0 Gy
fractions. The regional lymph nodes were treated in 187 patients (85%). There
were 151 patients (68%) who received adjuvant chemotherapy. Patients who received
chemotherapy were younger (median age, 48 years vs 64 years) and had more
positive lymph nodes (median, 5 vs 1) than patients not receiving chemotherapy.
Adjuvant hormonal therapy was utilized in 116 patients (53%). The median follow
up was 4.3 years. RESULTS: The actuarial 10-year local-regional failure rate was
11% (95% CI: 6.5% to 16.7%). The site of first failure was distant metastases in
75 patients (34%), local-regional recurrence in 11 patients (5%), and both sites
in three patients (1%); 60% had no evidence of disease at last follow-up. Of the
patients who presented with local-regional recurrence as first failure, nine
patients (82%) subsequently developed metastatic disease. The median time to
local-regional first failure was 1.3 years. The median time to distant metastases
after local-regional first failure was 0.3 years. DISCUSSION: Postmastectomy
radiation therapy is associated with an 89% rate of local-regional control in
this high-risk population. Patients who experience a local-regional recurrence
after radiation therapy are at a very high risk for metastatic disease. Radiation
therapy after mastectomy is recommended to optimize local-regional control for
high-risk breast cancer patients.
PMID- 10198731
TI - Assessing the impact of elective regional radiotherapy on survival.
AB - PURPOSE: Elective regional irradiation (ERI) of sites of likely tumor spread has
been common radiation oncology practice for decades. It is based, in part, on the
assumption that cancer often spreads in an orderly fashion and that an
improvement in regional control will increase survival. METHOD: The clinical data
regarding the impact of ERI on local-regional control vs survival are reviewed
for a variety of tumor sites. RESULTS: Improvements in survival with ERI have
been reported in some clinical situations. For most, however, survival
improvements have been difficult to realize. In most clinical situations, the
realistic improvement in survival that is achievable with ERI is small and would
be difficult to document in reasonably sized clinical trials. DISCUSSION: The
dose-response relationship for the impact of ERI on survival is discussed. A
hypothesis suggesting that a reduction in the dose of ERI may improve the
therapeutic ratio of ERI (with respect to its impact on survival) is presented.
PMID- 10198730
TI - Preoperative combined modality therapy with paclitaxel, carboplatin, prolonged
infusion 5-fluorouracil, and radiation therapy in localized esophageal cancer:
preliminary results of a Minnie Pearl Cancer Research Network phase II trial.
AB - PURPOSE: To evaluate the feasibility, toxicity, and therapeutic efficacy of 1
hour paclitaxel, carboplatin, continuous low-dose infusional 5-fluorouracil, and
concurrent radiation therapy administered preoperatively in patients with
localized esophageal cancer. PATIENT AND METHODS: Forty-nine patients with
localized esophageal cancer, of either squamous cell carcinoma or adenocarcinoma
histology, were enrolled into this phase II trial. All patients were candidates
for surgical resection and received the following neoadjuvant therapy:
paclitaxel, 200 mg/m2, 1 hour IV on days 1 and 22; carboplatin, AUC 6.0, IV on
days 1 and 22; 5-fluorouracil, 225 mg/m2/day, continuous IV infusion on days 1 to
42; and radiation therapy, 45 Gy, administered by 1.8-Gy daily fractions
beginning on day 1 of chemotherapy. Upon completion of this neoadjuvant regimen,
patients were reevaluated, and all responding patients were resected within 6
weeks of completing neoadjuvant treatment. RESULTS: Administration of this
combined modality regimen was associated with moderate toxicity and was tolerated
by most patients. Leukopenia (65%) and esophagitis (31%) were the most common
toxicities. Most patients did not require nutritional support. There were no
treatment-related deaths during neoadjuvant therapy; however, three patients (9%)
experienced postoperative death. Preliminary assessment of treatment efficacy is
encouraging, with 17 of 37 evaluable patients (46%) achieving pathologic complete
remission and an additional 11 patients (30%) having only microscopic residual
disease. CONCLUSIONS: This novel, combined-modality neoadjuvant approach for the
treatment of localized esophageal carcinoma is feasible and can be administered
with toxicity that compares favorably to previously reported neoadjuvant regimens
containing high-dose cisplatin. Preliminary assessment of efficacy is also
encouraging, with 46% of patients having pathologic complete response. Further
follow-up and larger numbers of patients are required to assess efficacy more
definitively.
PMID- 10198732
TI - Clinical relevance of vascular endothelial growth factor and thymidine
phosphorylase in patients with node-positive breast cancer treated with either
adjuvant chemotherapy or hormone therapy.
AB - PURPOSE: To determine the role of the two angiogenic peptides, vascular
endothelial growth factor (VEGF) and thymidine phosphorylase (TP) (the latter
also being a target enzyme for cytotoxicity of 5-fluorouracil and methotrexate),
and conventional prognostic factors in predicting relapse-free survival (RFS) and
overall survival (OS) probabilities in two cohorts of patients with node-positive
breast cancer (NPBC) treated with either adjuvant chemotherapy (CMF
[cyclophosphamide, methotrexate, 5-fluorouracil] schedule) or hormone therapy
(tamoxifen). PATIENTS AND METHODS: We studied two groups of 137 and 164 patients
with NPBC, median follow-up of 72 months for both, treated with adjuvant
chemotherapy or hormone therapy, respectively. The cytosolic levels of VEGF and
TP were determined in the primary tumor by original immunometric methods. The
association between VEGF and TP and of these angiogenic peptides with other
prognostic indicators were tested by using the Spearman correlation coefficient
(for continuous variables) or the Kolmogorov-Smirnov test (for dichotomous
variables). Results of the clinical outcome were analyzed by both univariate and
multivariate (for RFS only) Cox regression models in which VEGF and TP were
treated as continuous variables. RESULTS: In the CMF group, the concentrations of
VEGF and TP ranged from 5.8 to 7798 pg/mg of protein (median, 87.5 pg/mg) and
from 1.2 to 904 U/mg (median, 138.2 U/mg), respectively. There was no significant
association between the two angiogenic peptides. VEGF was not associated with any
other variable, whereas TP showed a positive association with age and an inverse
association with the number of involved nodes. In the tamoxifen group, the
concentrations of VEGF (5.9-2482; median, 79.3 pg/mg protein) and TP (6.1-1542;
median, 146.5 U/mg) were similar to those of the CMF group, and the two
angiogenic peptides were not correlated. VEGF was positively associated with age
and was inversely associated with estrogen receptor and progesterone receptor,
whereas TP was not associated with any other variable. Univariate analysis in the
CMF group showed that VEGF and TP were significantly predictive of both RFS and
OS. Likewise, the number of involved axillary nodes was significantly associated
with both RFS and OS. Univariate analysis in the tamoxifen group showed that TP
did not significantly influence either RFS or OS. On the contrary, VEGF levels
were significantly predictive of both RFS and OS, as were the number of involved
nodes, estrogen receptor concentrations, and progesterone receptor concentration.
In the multivariate analysis on RFS in the CMF group, VEGF, TP, their first-order
interaction term, and age were significant and independent predictive factors. In
the tamoxifen group, only VEGF and the number of involved nodes were significant
and independent predictive factors. DISCUSSION: The results of our study suggest
that high levels of TP and low levels of VEGF characterize the patients with NPBC
treated with adjuvant CMF who have the highest likelihood of favorable outcome.
Low levels of VEGF and the presence of less than three involved axillary nodes
characterize the patients with NPBC treated with adjuvant tamoxifen who have the
highest likelihood of favorable outcome. This information may be useful to plan
future studies to better select the patients with NPBC for conventional adjuvant
treatments as well as to monitor the efficacy of novel therapeutic strategies of
adjuvant therapy based on inhibition of angiogenesis.
PMID- 10198734
TI - Beta blockers: are they difficult to use in heart failure patients?
PMID- 10198733
TI - Oral etoposide for patients with metastatic gastric adenocarcinoma.
AB - PURPOSE: Oral administration of etoposide represents a pharmacokinetic advantage
over the traditional intermittent intravenous usage of this drug. This phase II
trial was undertaken to determine its activity against gastric adenocarcinoma in
chemotherapy-naive patients. PATIENTS AND METHODS: Patients with measurable,
unresectable, metastatic gastric carcinoma with performance status < or = 2 by
Zubrod scale were eligible. Patients had to have normal liver, renal, and bone
marrow functions. Written informed consent was obtained from all patients. The
starting dose of etoposide was 50 mg/m2/day, given orally daily for 21 days,
followed by a 7-day rest period. Oral etoposide was repeated every 28 days.
Response was evaluated after two courses. RESULTS: Twenty-eight patients were
registered. The median number of courses was two (range, 1 to 12; total, 69
courses). Twenty-six patients were evaluable for response and toxicity. Five
patients (19%; 95% confidence interval, 3% to 35%) achieved a partial response.
The median duration of response was 3.5 months. There was no treatment-related
death. Toxic effects were mild to moderate. CONCLUSIONS: Oral etoposide is
modestly active against gastric carcinoma. It is well tolerated by patients.
Further studies in combination with other active agents against gastric carcinoma
may be warranted.
PMID- 10198735
TI - Periprocedural creatine kinase-MB elevations: long-term impact and clinical
implications.
AB - Since the introduction of percutaneous transluminal coronary angioplasty (PTCA),
percutaneous intervention with balloon catheters, stents, and atherectomy devices
has become a widely accepted practice. The persistent complication of non-Q-wave
myocardial infarction (MI), as evidenced by increased cardiac enzyme levels after
intervention, has aroused only moderate concern because its incidence was
perceived to be small and not clinically relevant. With more systematic
assessments of cardiac enzymes--specifically, creatine kinase (CK) and its MB
isoform--evidence has begun to clarify both the incidence and the prognosis of
periprocedural non-Q-wave MI: It appears to occur nearly three times more often
than is clinically evident across all device types (8 to 9% of all interventions)
and is directly and continuously associated with adverse outcomes, including late
death. Although directional and rotational atherectomy improve angiographic
outcome compared with PTCA, periprocedural infarction occurs at least twice as
often with these newer technologies; the incidence associated with stent
placement is comparable to and possibly higher than that of PTCA. Factors that
may cause elevated CK-MB levels include distal embolization, side branch
occlusion, thrombus, and coronary spasm. Analyses of the major trials of platelet
glycoprotein (GP) IIb/IIIa receptor inhibitors, a class of potent antiplatelet
agents, show striking effectiveness of these drugs in reducing the incidence of
"enzyme-only" or "silent" MI and in improving long-term clinical outcomes. The
findings implicate platelet mediation in the occurrence of periprocedural
infarction and suggest an important role for antiplatelet the